FN Thomson Reuters Web of Science™ VR 1.0 PT J AU McCoy, MT Jayanthi, S Beauvais, G Ladenheim, B Krasnova, I Martin, T Hodges, AB Cadet, JL AF McCoy, Michael Thomas Jayanthi, Subramaniam Beauvais, Genevieve Ladenheim, Bruce Krasnova, Irina Martin, Tracey Hodges, Amber B. Cadet, Jean Lud TI Methamphetamine (METH) preconditioning causes subsensitivity to METH-induced acute effects on the expression of immediate early genes SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [McCoy, Michael Thomas; Jayanthi, Subramaniam; Beauvais, Genevieve; Ladenheim, Bruce; Krasnova, Irina; Martin, Tracey; Hodges, Amber B.; Cadet, Jean Lud] NIDA, Mol Neuropsychiat Res Branch, DHHS, NIH,IRP, Baltimore, MD USA. [Hodges, Amber B.] Morgan State Univ, Baltimore, MD 21239 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402612 ER PT J AU McMillin, SM Heusel, M Costanzi, S Wess, J AF McMillin, Sara Margaret Heusel, Moritz Costanzi, Stefano Wess, Jurgen TI Multiple transmembrane segments are involved in M3 muscarinic receptor dimerization/oligomerization SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [McMillin, Sara Margaret; Heusel, Moritz; Costanzi, Stefano; Wess, Jurgen] NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708403569 ER PT J AU McNally, J Stasevich, T Mazza, D Mueller, F AF McNally, James Stasevich, Timothy Mazza, Davide Mueller, Florian TI The live cell kinetics of transcription SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [McNally, James; Stasevich, Timothy; Mazza, Davide; Mueller, Florian] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402076 ER PT J AU Mereu, M Chun, L Kopajtic, TA Shook, M French-Evans, D Prisinzano, TA Newman, AH Katz, JL Tanda, G AF Mereu, Maddalena Chun, Lauren Kopajtic, Theresa A. Shook, Matthew French-Evans, Dawn Prisinzano, Thomas A. Newman, Amy H. Katz, Jonathan L. Tanda, Gianluigi TI Subjective and neurochemical effects of modafinil in mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Mereu, Maddalena; Chun, Lauren; Kopajtic, Theresa A.; Shook, Matthew; French-Evans, Dawn; Katz, Jonathan L.; Tanda, Gianluigi] NIDA, Psychobiol Sect, NIH, DHHS, Baltimore, MD USA. [Newman, Amy H.] NIDA, Med Chem Sect, NIH, DHHS, Baltimore, MD USA. [Prisinzano, Thomas A.] Univ Kansas, Dept Med Chem, Lawrence, KS 66045 USA. RI Tanda, Gianluigi/B-3318-2009 OI Tanda, Gianluigi/0000-0001-9526-9878 NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708405339 ER PT J AU Meza-Carmen, V Pacheco-Rodriguez, G Kato, J Kang, GS Donati, C Vichi, A Zhang, CY Payne, M El-Chemaly, S Moss, J Vaughan, M AF Meza-Carmen, Victor Pacheco-Rodriguez, Gustavo Kato, Jiro Kang, Gi Soo Donati, Chiara Vichi, Alessandro Zhang, Chunyi Payne, Michael El-Chemaly, Souheil Moss, Joel Vaughan, Martha TI Regulation of growth factor receptor degradation by ADP-ribosylation factor-domain protein (ARD) 1 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Meza-Carmen, Victor; Pacheco-Rodriguez, Gustavo; Kato, Jiro; Kang, Gi Soo; Donati, Chiara; Vichi, Alessandro; Zhang, Chunyi; Payne, Michael; El-Chemaly, Souheil; Moss, Joel; Vaughan, Martha] NIH, Cardiovasc & Pulm Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402944 ER PT J AU Middleton, A Andrews, K Roseland, J Zhao, CW Holden, J Dwyer, J Saldanha, L AF Middleton, Angela Andrews, Karen Roseland, Janet Zhao, Cuiwei Holden, Joanne Dwyer, Johanna Saldanha, Leila TI Preliminary evaluation of omega-3 dietary supplement label information for products in the Dietary Supplement Ingredient Database (DSID) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Middleton, Angela; Andrews, Karen; Roseland, Janet; Zhao, Cuiwei; Holden, Joanne] ARS, USDA, Beltsville, MD USA. [Dwyer, Johanna; Saldanha, Leila] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708403298 ER PT J AU Milanesio, PA Battesti, A Mann, J Bougdour, A Gottesman, S AF Milanesio, Paola Andrea Battesti, Aurelia Mann, Jessica Bougdour, Alexandre Gottesman, Susan TI Study of the molecular interaction between RssB Adaptor protein and IraP Anti-Adaptor protein in Escherichia coli SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Milanesio, Paola Andrea; Battesti, Aurelia; Mann, Jessica; Gottesman, Susan] NIH, LMB, Bethesda, MD 20892 USA. [Bougdour, Alexandre] Univ Grenoble, Grenoble, France. RI Bougdour, Alexandre/K-3795-2014 OI Bougdour, Alexandre/0000-0002-5895-0020 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406675 ER PT J AU Milgram, SL AF Milgram, Sharon L. TI Techniques for Building Student Confidence in a Research Setting SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Milgram, Sharon L.] NIH, Off Director, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708401757 ER PT J AU Miller, DS Hawkins, BT Wang, XQ AF Miller, David S. Hawkins, Brian T. Wang, Xueqian TI Activating blood-brain barrier (BBB) PKC beta 1 reverses in vitro and in vivo induction of P-glycoprotein (P-gp) by dioxin SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Miller, David S.; Hawkins, Brian T.; Wang, Xueqian] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708403934 ER PT J AU Miller, RL Somparn, P Yu, MJ Knepper, M AF Miller, R. Lance Somparn, Poorichaya Yu, Ming-Jiun Knepper, Mark TI Identification of vasopressin-dependent early response genes in mpkCCD cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Miller, R. Lance; Somparn, Poorichaya; Knepper, Mark] NIH, Bethesda, MD 20892 USA. [Yu, Ming-Jiun] Natl Taiwan Univ, Taipei 10764, Taiwan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708405885 ER PT J AU Miller, TW Wang, EA Gould, S Stein, EV Roberts, DD AF Miller, Thomas Wesley Wang, Evelyn A. Gould, Serge Stein, Erica V. Roberts, David D. TI A novel role for hydrogen sulfide: enhancement of T-cell activation/proliferation and its regulation by thrombospondin-1/CD47 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Miller, Thomas Wesley; Wang, Evelyn A.; Gould, Serge; Stein, Erica V.; Roberts, David D.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Stein, Erica V.] George Washington Univ, Washington, DC USA. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402899 ER PT J AU Miller, Y Ma, BY Nussinov, R AF Miller, Yifat Ma, Buyong Nussinov, Ruth TI Alzheimer A beta amyloid tubular fibrils: Insight into polymorphism SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Miller, Yifat] NCI, NIH, Frederick, MD 21701 USA. [Ma, Buyong; Nussinov, Ruth] NCI, SAIC Frederick, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708404493 ER PT J AU Mishra, S Sahyoun, N Mehta, M Hue, TF Miljkovic, I Satterfield, S De Rekeneire, N Harris, TB AF Mishra, Suruchi Sahyoun, Nadine Mehta, Mira Hue, Trisha F. Miljkovic, Iva Satterfield, Suzanne De Rekeneire, Nathalie Harris, Tamara B. TI Hyperleptinemia, adiposity and risk of metabolic syndrome in older adults SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Mishra, Suruchi] Washington Ctr Clin Res, Washington, DC USA. [Sahyoun, Nadine; Mehta, Mira] Univ Maryland, College Pk, MD 20742 USA. [Hue, Trisha F.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Miljkovic, Iva] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Satterfield, Suzanne] Univ Tennessee, Memphis Field Ctr, Memphis, TN USA. [De Rekeneire, Nathalie] Yale Univ, Sch Med, New Haven, CT USA. [Harris, Tamara B.] NIA, Bethesda, MD 20892 USA. RI Sahyoun, Nadine/G-2608-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402131 ER PT J AU Mizurini, DD Calvo, E Francischetti, I Monteiro, R AF Mizurini, Daniella de Moraes Calvo, Eric Francischetti, Ivo Monteiro, Robson TI Molecular mechanisms involved in the antithrombotic activity of aegyptin, a novel mosquito-derived collagen-binding protein SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Mizurini, Daniella de Moraes; Monteiro, Robson] Univ Fed Rio de Janeiro, Inst Bioquim Med, Rio De Janeiro, Brazil. [Calvo, Eric; Francischetti, Ivo] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406537 ER PT J AU Moaddab, N Han, RJ Zukowska, Z Thorsell, A AF Moaddab, Naz Han, Ruijun Zukowska, Zofia Thorsell, Annika TI Neuropeptide Y and Prenatal Stress: NPY's role in early programming for Obesity and Anxiety in Adulthood SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Moaddab, Naz; Han, Ruijun] Georgetown Univ, Washington, DC USA. [Zukowska, Zofia] Univ Minnesota, Minneapolis, MN USA. [Thorsell, Annika] NIAAA, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406072 ER PT J AU Modi, HR Shimshoni, JA Basselin, M Li, LO Coleman, RA Rapoport, SI AF Modi, Hiren R. Shimshoni, Jakob A. Basselin, Mireille Li, Lei O. Coleman, Rosalind A. Rapoport, Stanley I. TI Is valproate's brain target in treating bipolar disorder an arachidonic acid selective acyl-coA synthetase? SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Modi, Hiren R.; Shimshoni, Jakob A.; Basselin, Mireille; Rapoport, Stanley I.] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. [Shimshoni, Jakob A.] Univ Washington, Dept Pharmaceut, Seattle, WA 98195 USA. [Li, Lei O.; Coleman, Rosalind A.] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402836 ER PT J AU Mohanraj, R Mukhopadhyay, P Batkai, S Patel, V Horvath, B Wink, DA Pacher, P Mechoulam, R AF Mohanraj, Rajesh Mukhopadhyay, Partha Batkai, Sandor Patel, Vivek Horvath, Bela Wink, David A. Pacher, Pal Mechoulam, Raphael TI Cannabidiol Attenuates Cardiac Dysfunction, Oxidative Stress, Fibrosis, Inflammatory and Cell Death Signaling Pathways in Diabetic Cardiomyopathy SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Mohanraj, Rajesh; Mukhopadhyay, Partha; Batkai, Sandor; Patel, Vivek; Horvath, Bela; Pacher, Pal] NIH, Sect Oxidat Stress Tissue Injury, Rockville, MD USA. [Wink, David A.] NCI, Bethesda, MD 20892 USA. [Mechoulam, Raphael] Hebrew Univ Jerusalem, Dept Med Chem & Nat Prod, Jerusalem, Israel. RI Batkai, Sandor/H-7983-2014 NR 0 TC 0 Z9 0 U1 0 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708405671 ER PT J AU Mohanraj, R Mukhopadhyay, P Batkai, S Patel, V Horvath, B Hasko, G Liaudet, L Mackie, K Pacher, P AF Mohanraj, Rajesh Mukhopadhyay, Partha Batkai, Sandor Patel, Vivek Horvath, Bela Hasko, Gyoergy Liaudet, Lucas Mackie, Ken Pacher, Pal TI CB1 RECEPTOR ACTIVATION INDUCES ROS-DEPENDENT AND INDEPENDENT MAPK ACTIVATION AND CELL DEATH IN HUMAN ENDOTHELIAL CELLS AND CARDIOMYOCYTES SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Mohanraj, Rajesh; Mukhopadhyay, Partha; Batkai, Sandor; Patel, Vivek; Horvath, Bela; Pacher, Pal] NIH, Sect Oxidat Stress Tissue Injury, Bethesda, MD 20892 USA. [Hasko, Gyoergy] UMDNJ NJ, Newark, NY USA. [Liaudet, Lucas] Univ Lausanne, Lausanne, Switzerland. [Mackie, Ken] Indiana Univ, Bloomington, IN USA. RI Batkai, Sandor/H-7983-2014; Liaudet, Lucas/E-1322-2017 OI Liaudet, Lucas/0000-0003-2670-4930 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708404052 ER PT J AU Moitra, K McGee, K Sawitzke, J Yuhki, N Robey, R Bates, S Dean, M AF Moitra, Karobi McGee, Kate Sawitzke, Julie Yuhki, Naoya Robey, Rob Bates, Susan Dean, Michael TI Genomic Analysis of Etoposide Resistance Reveals Multiple Alterations of Gene and microRNA Expression SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Moitra, Karobi; McGee, Kate; Sawitzke, Julie; Dean, Michael] NCI, CIP, NIH, Frederick, MD 21701 USA. [Yuhki, Naoya] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. [Robey, Rob; Bates, Susan] NIH, Med Oncol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406514 ER PT J AU Mondul, A Kopp, W Virtamo, J Albanes, D AF Mondul, Alison Kopp, William Virtamo, Jarmo Albanes, Demetrius TI Alpha-tocopherol and beta-carotene supplementation and change in vascular endothelial growth factor (VEGF) A, VEGF-C, and VEGF-D levels SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Mondul, Alison; Albanes, Demetrius] NCI, NIH, Rockville, MD USA. [Kopp, William] SAIC NIH, Frederick, MD USA. [Virtamo, Jarmo] Natl Inst Hlth & Welf, Helsinki, Finland. RI Albanes, Demetrius/B-9749-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402187 ER PT J AU Moon, K Gottesman, S AF Moon, Kyung Gottesman, Susan TI Competition among small RNAs in Escherichia coli SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Moon, Kyung; Gottesman, Susan] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402618 ER PT J AU Moshkovich, N Nisha, P Boyle, PJ Thompson, BA Dale, RK Lei, EP AF Moshkovich, Nellie Nisha, Parul Boyle, Patrick J. Thompson, Brandi A. Dale, Ryan K. Lei, Elissa P. TI RNAi-independent role for Argonaute2 in CTCF/CP190 insulator function SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Moshkovich, Nellie; Nisha, Parul; Boyle, Patrick J.; Thompson, Brandi A.; Dale, Ryan K.; Lei, Elissa P.] NIDDK, LCDB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402629 ER PT J AU Mukhopadhyay, P Rajesh, M Batkai, S Pan, H Mukhopadhyay, B Hasko, G Mackie, K Pacher, P AF Mukhopadhyay, Partha Rajesh, Mohanraj Batkai, Sandor Pan, Hao Mukhopadhyay, Bani Hasko, Gyoergy Mackie, Ken Pacher, Pal TI OPPOSING EFFECTS OF CB1 AND CB2 RECEPTORS ON INFLAMMATION, OXIDATIVE STRESS, AND CELL DEATH IN NEPROPATHY SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Mukhopadhyay, Partha; Rajesh, Mohanraj; Batkai, Sandor; Pan, Hao; Mukhopadhyay, Bani; Pacher, Pal] NIAAA, NIH, Rockville, MD 20852 USA. [Hasko, Gyoergy] UMDNJ New Jersey Med Sch, Newark, NJ USA. [Mackie, Ken] Indiana Univ, Bloomington, IN USA. RI Batkai, Sandor/H-7983-2014 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708401160 ER PT J AU Nader, MA Blaylock, BL Banala, A Newman, AH AF Nader, Michael A. Blaylock, Brandi L. Banala, Ashwini Newman, Amy Hauck TI Effects of the novel dopamine D3 compound PG 619 on cocaine-food choice in rhesus monkeys SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Nader, Michael A.; Blaylock, Brandi L.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. [Banala, Ashwini; Newman, Amy Hauck] NIDA Intramural Res Program, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708405353 ER PT J AU Nagineni, C Kommineni, VK Ganjbaksh, N Hooks, JJ Detrick, B AF Nagineni, Chandra Kommineni, Vijay K. Ganjbaksh, Nader Hooks, John J. Detrick, Barbara TI CCR-3 ligands, CCL-5, 7, 11 and 26, are induced in human retinal cells by inflammatory cytokines: Potential role in age-related macular degeneration SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Nagineni, Chandra; Kommineni, Vijay K.; Ganjbaksh, Nader; Hooks, John J.] NEI, NIH, Bethesda, MD 20892 USA. [Detrick, Barbara] Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708403427 ER PT J AU Nakamura, T Fukumoto, S Yamada, Y AF Nakamura, Takashi Fukumoto, Satoshi Yamada, Yoshihiko TI Diverse functions of Epiprofin in ectodermal organogenesis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Nakamura, Takashi; Fukumoto, Satoshi] Tohoku Univ, Dept Oral Hlth & Dev Sci, Grad Sch Dent, Sendai, Miyagi 980, Japan. [Nakamura, Takashi; Yamada, Yoshihiko] Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402862 ER PT J AU Nansel, TR Liu, AY Lipsky, LM Haynie, DL Mehta, SN Laffel, LMB AF Nansel, Tonja R. Liu, Aiyi Lipsky, Leah M. Haynie, Denise L. Mehta, Sanjeev N. Laffel, Lori M. B. TI Differences in diet quality between weekdays and weekends: utility of a random effects model SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Nansel, Tonja R.; Liu, Aiyi; Lipsky, Leah M.; Haynie, Denise L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Mehta, Sanjeev N.; Laffel, Lori M. B.] Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708403308 ER PT J AU Naranjo-Suarez, S Carlson, BA Yoo, MH Tsuji, P Gladyshev, VN Hatfield, DL AF Naranjo-Suarez, Salvador Carlson, Bradley A. Yoo, Min-Hyuk Tsuji, Petra Gladyshev, Vadim N. Hatfield, Dolph L. TI Hypoxic HIF-independent regulation of thioredoxin reductase 1 expression SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Naranjo-Suarez, Salvador; Carlson, Bradley A.; Yoo, Min-Hyuk; Tsuji, Petra; Hatfield, Dolph L.] NCI NIH, MBSS LCP, Bethesda, MD USA. [Gladyshev, Vadim N.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Gladyshev, Vadim N.] Harvard Univ, Sch Med, Boston, MA USA. RI Gladyshev, Vadim/A-9894-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708400014 ER PT J AU Neutzner, A Neutzner, M Benischke, AS Ryu, SW Youle, RJ Karbowski, M AF Neutzner, Albert Neutzner, Melanie Benischke, Anne-Sophie Ryu, Seung-Wook Youle, Richard J. Karbowski, Mariusz TI Calnexin levels are regulated by the ER localized ubiquitin ligase Nixin SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Neutzner, Albert; Neutzner, Melanie; Benischke, Anne-Sophie] Univ Basel Hosp, Dept Biomed, CH-4031 Basel, Switzerland. [Ryu, Seung-Wook] Korea Adv Inst Sci & Technol, Taejon 305701, South Korea. [Youle, Richard J.] NINDS, NIH, Bethesda, MD 20892 USA. [Karbowski, Mariusz] Univ Maryland, Sch Med, Ctr Biomed Engn & Technol, Baltimore, MD 21201 USA. [Karbowski, Mariusz] Univ Maryland, Sch Med, Dept Biochem & Mol Biolog, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406416 ER PT J AU Nogare, DD Chitnis, A AF Nogare, Damian Dalle Chitnis, Ajay TI Sprouty proteins and RTK pathway antagonism in the lateral line primordium SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Nogare, Damian Dalle; Chitnis, Ajay] NICHD, Sect Neural Dev Dynam, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402461 ER PT J AU Ohana, E Shcheynikov, N Muallem, S AF Ohana, Ehud Shcheynikov, Nikolay Muallem, Shmuel TI Determinants of coupled transport and uncoupled current by the electrogenic SLC26 transporters SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Ohana, Ehud; Shcheynikov, Nikolay; Muallem, Shmuel] NIDCR, MPTB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708400599 ER PT J AU Oshea, JJ AF Oshea, John J. TI Insights into T Cell Differentiation using Genome-wide Analysis of Epigenetic Changes and Transcription Factor Binding SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Oshea, John J.] NIAMS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708404562 ER PT J AU Oubrahim, H Sengupta, DC Wilson, BA Chock, PB AF Oubrahim, Hammou Sengupta, Deepali C. Wilson, Brenda A. Chock, P. Boon TI Pasteurella multocida toxin (PMT) activates the ERK signaling pathway, in part, by upregulating CTGF expression SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Oubrahim, Hammou; Sengupta, Deepali C.; Chock, P. Boon] NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. [Wilson, Brenda A.] Univ Illinois, Dept Microbiol, Urbana, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406674 ER PT J AU Oum, JH Som, I Eszterhas, S Little, J Fiering, S Dean, A AF Oum, Ji-Hyun Som, Indrani Eszterhas, Susan Little, Jane Fiering, Steven Dean, Ann TI DEVELOPMENTAL REGULATION OF THE MURINE beta-GLOBIN LOCUS SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Oum, Ji-Hyun; Som, Indrani; Eszterhas, Susan; Little, Jane; Dean, Ann] NIDDK, NIH, Bethesda, MD USA. [Fiering, Steven] Dartmouth Med Sch, Lebanon, NH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406332 ER PT J AU Paliege, A Kahl, T Seidel, S Schnermann, J Bachmann, S AF Paliege, Alexander Kahl, Thomas Seidel, Saskia Schnermann, Juergen Bachmann, Sebastian TI Annexin A1 inhibits macula densa Cyclooxygenase 2 and Nitric oxide Synthase 1 expression SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Paliege, Alexander; Kahl, Thomas; Seidel, Saskia; Bachmann, Sebastian] Charite, Dept Anat, D-13353 Berlin, Germany. [Schnermann, Juergen] NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708400496 ER PT J AU Pan, YP Nussinov, R AF Pan, Yongping Nussinov, Ruth TI Sequence-Dependent Specific p53-Response Element Interactions Direct P53 organization and Control Transcription Selectivity SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Pan, Yongping; Nussinov, Ruth] NCI, Basic Sci Program, SAIC, Frederick, MD 21701 USA. [Nussinov, Ruth] Tel Aviv Univ, IL-69978 Tel Aviv, Israel. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402596 ER PT J AU Pang, ALY Clark, J Chan, WY Rennert, OM AF Pang, Alan L. Y. Clark, Jessica Chan, Wai-Yee Rennert, Owen M. TI The tissue-restricted expression of N-alpha-acetyltransferase catalytic subunit gene Arrest Defective 1B in the mouse and human is regulated by CpG island methylation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Pang, Alan L. Y.; Clark, Jessica; Chan, Wai-Yee; Rennert, Owen M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Chan, Wai-Yee] Chinese Univ Hong Kong, Sch Biomed Sci, Fac Med, Shatin, Hong Kong, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402614 ER PT J AU Pang, T Benicky, J Wang, J Sanchez-Lemus, E Saavedra, JM AF Pang, Tao Benicky, Julius Wang, Juan Sanchez-Lemus, Enrique Saavedra, Juan M. TI Telmisartan decreases the innate immune response to LPS in circulating human monocytes through PPAR. activation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Pang, Tao; Benicky, Julius; Wang, Juan; Sanchez-Lemus, Enrique; Saavedra, Juan M.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708405639 ER PT J AU Panlilio, LV Yasar, S Thorndike, EB Goldberg, SR Schindler, CW AF Panlilio, Leigh V. Yasar, Sevil Thorndike, Eric B. Goldberg, Steven R. Schindler, Charles W. TI Mediating behavior in delayed spatial matching procedures as an animal model of memory rehearsal SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Panlilio, Leigh V.; Yasar, Sevil; Thorndike, Eric B.; Goldberg, Steven R.; Schindler, Charles W.] NIDA IRP, NIH, DHHS, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708405370 ER PT J AU Park, JH Lee, SB Park, MH AF Park, Jong Hwan Lee, Seung Bum Park, Myung Hee TI Production of active recombinant eIF5A: Reconstitution in E. coli of eukaryotic hypusine modification of eIF5A by its coexpression with modifying enzymes SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Park, Jong Hwan; Lee, Seung Bum; Park, Myung Hee] NIDCR, OPCB, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708404521 ER PT J AU Park, JH Johansson, HE Park, MH AF Park, Jong Hwan Johansson, Hans E. Park, Myung Hee TI Bacterial elongation factor P (EF-P): In vivo evidence for its posttranslational modification by YjeA and YjeK SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Park, Jong Hwan; Park, Myung Hee] NIDCR, OPCB, NIH, Bethesda, MD USA. [Johansson, Hans E.] BioSearch, Novato, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402674 ER PT J AU Patchell, FS Ruder, EH Mitchell, DC Jacques, PF Hartman, TJ Goldman, MB AF Patchell, Fawn S. Ruder, Elizabeth H. Mitchell, Diane C. Jacques, Paul F. Hartman, Terryl J. Goldman, Marlene B. TI Comparison of selected nutrient intakes between the Block FFQ and unannounced 24-hour recalls in periconceptional couples SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Patchell, Fawn S.; Mitchell, Diane C.; Hartman, Terryl J.] Penn State Univ, University Pk, PA 16802 USA. [Ruder, Elizabeth H.] NCI, Bethesda, MD 20892 USA. [Jacques, Paul F.] Tufts Univ, Jean Mayer USDA HNRCA, Boston, MA 02111 USA. [Goldman, Marlene B.] Dartmouth Med Sch, Dept Obstet & Gynecol, Lebanon, NH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708405195 ER PT J AU Patel, RA Xie, ZH Kirk, D AF Patel, Roshni Abee Xie, Zhihui Kirk, Druey TI Studies on the pathogenesis of Systemic Capillary Leak Syndrome SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Patel, Roshni Abee; Xie, Zhihui; Kirk, Druey] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708403452 ER PT J AU Perruzza, S Fernandes, J Hirshberg, S Cook, E Lofgren, I AF Perruzza, Stephanie Fernandes, Jill Hirshberg, Shira Cook, Emily Lofgren, Ingrid TI Effects of weight status on eating in college females SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Perruzza, Stephanie] Univ Rhode Isl, Narragansett, RI USA. [Fernandes, Jill] Southcoast Hlth Syst & Southcoast Hosp Grp, Taunton, MA USA. [Hirshberg, Shira] Univ Rhode Isl, Saunderstown, RI USA. [Cook, Emily] NIH, Rockville, MD USA. [Lofgren, Ingrid] Univ Rhode Isl, Kingston, RI 02881 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406958 ER PT J AU Pisitkun, T Knepper, MA AF Pisitkun, Trairak Knepper, M. A. TI NHLBI-AbDesigner, artificial intelligence-based software for design of peptide-directed antibodies SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Pisitkun, Trairak; Knepper, M. A.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406495 ER PT J AU Post, JD Colsch, B Bull, G Gouty, S Cox, BM Woods, AS AF Post, Jeremy D. Colsch, Benoit Bull, Gregory Gouty, Shawn Cox, Brian M. Woods, Amina S. TI Tracking time dependent lipid profile changes in controlled cortical impact rat brain injuries using imaging mass spectrometry SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Post, Jeremy D.] NIDA, NIH, IRP, Henry Jackson Fdn, Baltimore, MD USA. [Bull, Gregory; Gouty, Shawn; Cox, Brian M.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708400047 ER PT J AU Pratto, F Bellani, M Camerini-Otero, RD AF Pratto, Florencia Bellani, Marina Camerini-Otero, Rafael Daniel TI Mouse models for the study of SPO11 splicing isoforms SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Pratto, Florencia; Camerini-Otero, Rafael Daniel] NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD USA. [Bellani, Marina] NIA, LMG, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406320 ER PT J AU Psaki, S Bhutta, Z Caulfield, L Checkley, W AF Psaki, Stephanie Bhutta, Zulfiqar Caulfield, Laura Checkley, William CA MAL-ED Network TI Multi-country household food security score is associated with lower height for age Z scores SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Psaki, Stephanie; Checkley, William] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Psaki, Stephanie; Caulfield, Laura] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Bhutta, Zulfiqar] Aga Khan Univ, Karachi, Pakistan. [Checkley, William] Johns Hopkins Sch Med, Baltimore, MD USA. RI Nguyen, Giang/D-9027-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708401876 ER PT J AU Pulakat, L Raja, K Gavini, N AF Pulakat, Lakshmi Raja, Kumaraguru Gavini, Nara TI Characterization of a NarH-interacting Protein that Regulates Anaerobic Growth of Pseudomonas aeruginosa SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Pulakat, Lakshmi] Univ Missouri, Columbia, MO USA. [Pulakat, Lakshmi] Harry S Truman VAMC, Columbia, MO USA. [Raja, Kumaraguru] Bowling Green State Univ, Bowling Green, OH 43403 USA. [Gavini, Nara] NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402642 ER PT J AU Rada, B Leto, TL AF Rada, Balazs Leto, Thomas L. TI The redox-active Pseudomonas virulence factor pyocyanin induces formation of neutrophil extracellular traps SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Rada, Balazs; Leto, Thomas L.] NIAID, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402265 ER PT J AU Ramadan, E Basselin, M Rao, J Chang, LS Chen, M Ma, KZ Rapoport, SI AF Ramadan, Epolia Basselin, Mireille Rao, Jagadeesh Chang, Lisa Chen, Mei Ma, Kaizong Rapoport, Stanley I. TI Chronic Lamotrigine Blocks NMDA Receptor-Mediated Brain Arachidonic Acid Signaling in Unanesthetized Rats SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Ramadan, Epolia; Basselin, Mireille; Rao, Jagadeesh; Chang, Lisa; Chen, Mei; Ma, Kaizong; Rapoport, Stanley I.] NIA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708405377 ER PT J AU Ramsden, C Hibbeln, J Majchrzak, S Davis, J AF Ramsden, Christopher Hibbeln, Joseph Majchrzak, Sharon Davis, John TI Omega-6 specific PUFA diets increase risk of CHD compared to mixed polyunsaturates: a meta-analysis of randomized controlled trials SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Ramsden, Christopher; Hibbeln, Joseph; Majchrzak, Sharon] NIAAA, NIH, LMBB, SNN, Bethesda, MD USA. [Davis, John] Univ Illinois, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708405073 ER PT J AU Rao, DK Ambudkar, SV Mayer, M AF Rao, Divya K. Ambudkar, Suresh V. Mayer, Michael TI A Combination of Low Doses of Curcumin and Gramicidin Selectively kills Cancer Cells that Express Multidrug Resistance-linked ABCG2 Transporter SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Rao, Divya K.; Mayer, Michael] Univ Michigan, Ann Arbor, MI 48109 USA. [Ambudkar, Suresh V.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RI Mayer, Michael/C-1299-2010 OI Mayer, Michael/0000-0002-6148-5756 NR 0 TC 0 Z9 0 U1 0 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406750 ER PT J AU Rao, JS Kim, HW Rapoport, SI AF Rao, Jagadeesh S. Kim, Hyung-Wook Rapoport, Stanley I. TI Upregulation of neuroinflammation and arachidonic acid cascade markers and loss of synaptic markers in frontal cortex from schizophrenic patients SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Rao, Jagadeesh S.; Kim, Hyung-Wook; Rapoport, Stanley I.] NIH, Signal Transduct Unit, BPMS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708400107 ER PT J AU Rapp, PR AF Rapp, Peter R. TI Lifespan, mindspan, and the aging brain SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Rapp, Peter R.] NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708403591 ER PT J AU Reese, EA Kim, HW Rapoport, SI Rao, JS AF Reese, Edmund A. Kim, Hyung-Wook Rapoport, Stanley I. Rao, Jagadeesh S. TI Altered Expression of G-protein subunits and GRKs in Alzheimer's Disease SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Reese, Edmund A.; Kim, Hyung-Wook; Rapoport, Stanley I.; Rao, Jagadeesh S.] NIA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708404748 ER PT J AU Rochman, M Furusawa, T Bustin, M AF Rochman, Mark Furusawa, Takashi Bustin, Michael TI Elevated embryonic expression of chromatin architectural protein HMGN5 alters higher order chromatin organization and leads to postnatal cardiac malfunction SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Rochman, Mark; Furusawa, Takashi; Bustin, Michael] NCI, Lab Metab, Bethesda, MD 20892 USA. RI Bustin, Michael/G-6155-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406333 ER PT J AU Rochman, Y Leonard, WJ AF Rochman, Yrina Leonard, Warren J. TI THE IMPORTANCE OF STAT5 ACTIVATION IN THYMIC STROMAL LYMPHOPOIETIN MEDIATED SIGNALING IN MOUSE AND HUMAN T CELLS. SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Rochman, Yrina; Leonard, Warren J.] NHLBI, DHHS, LMI, DIR,NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402857 ER PT J AU Roof, RA Free, RB Duan, LH Urizar, E Furman, CA Conroy, JL Titus, SA Southall, N Javitch, JA Sibley, DR AF Roof, Rebecca A. Free, R. Benjamin Duan, Lihua Urizar, Eneko Furman, Cheryse A. Conroy, Jennie L. Titus, Steven A. Southall, Noel Javitch, Jonathan A. Sibley, David R. TI Development of High Throughput Screening Assays for the Discovery of Functionally-Selective D-2 Dopamine Receptor Ligands SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Roof, Rebecca A.; Free, R. Benjamin; Furman, Cheryse A.; Conroy, Jennie L.; Sibley, David R.] NINDS, Mol Neuropharmacol Sect, NIH, Rockville, MD USA. [Duan, Lihua; Urizar, Eneko; Javitch, Jonathan A.] Columbia Univ, Ctr Mol Recognit, New York, NY USA. [Titus, Steven A.; Southall, Noel] NIH, NIH Chem Genom Ctr, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708405394 ER PT J AU Roseland, JM Andrews, KW Zhao, CW Middleton, A Holden, JM Dwyer, JT Douglass, LW Saldanha, LG AF Roseland, Janet Maxwell Andrews, Karen W. Zhao, Cuiwei Middleton, Angela Holden, Joanne M. Dwyer, Johanna T. Douglass, Larry W. Saldanha, Leila G. TI Study results for children's multivitamin/minerals (MVMs) for the Dietary Supplement Ingredient Database (DSID) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Roseland, Janet Maxwell; Andrews, Karen W.; Zhao, Cuiwei; Middleton, Angela; Holden, Joanne M.] ARS, Nutrient Data Lab, USDA, BNHRC, Beltsville, MD USA. [Dwyer, Johanna T.; Saldanha, Leila G.] NIH, Office Dietary Supplements, DHHS, Bethesda, MD 20892 USA. [Douglass, Larry W.] Univ Maryland, Longmont, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708401976 ER PT J AU Rosenbaek, LL Knepper, MA Fenton, RA AF Rosenbaek, Lena Lindtoft Knepper, Mark A. Fenton, Robert A. TI Novel vasopressin-regulated phosphorylation site of the NaCl co-transporter, NCC SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Rosenbaek, Lena Lindtoft; Fenton, Robert A.] Aarhus Univ, Dept Anat, Water & Salt Res Ctr, Aarhus, Denmark. [Knepper, Mark A.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708400490 ER PT J AU Roudier, E Olfert, MI Perry, ME Birot, O AF Roudier, Emilie Olfert, Mark I. Perry, Mary E. Birot, Olivier TI Murine Double Minute-2 is a new regulator of physiopathological angio-adaptation in cardiac and skeletal muscles SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Roudier, Emilie; Birot, Olivier] York Univ, Muscle Hlth Res Ctr, Toronto, ON M3J 2R7, Canada. [Olfert, Mark I.] W Virgina Univ, Div Exercise Physiol, Morgantown, WV USA. [Perry, Mary E.] NCI, Lab Prot Dynam & Signaling, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708401237 ER PT J AU Rouquette-Jazdanian, AK Akpan, IO Barr, VA Sommers, CL Samelson, LE AF Rouquette-Jazdanian, Alexandre Katchaz Akpan, Itoro O. Barr, Valarie A. Sommers, Connie L. Samelson, Lawrence E. TI Role of Bam32 in TCR-induced Erk activation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Rouquette-Jazdanian, Alexandre Katchaz; Akpan, Itoro O.; Barr, Valarie A.; Sommers, Connie L.; Samelson, Lawrence E.] NCI, LCMB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402932 ER PT J AU Saeed, F Hoffert, J Pisitkun, T Knepper, M AF Saeed, Fahad Hoffert, Jason Pisitkun, Trairak Knepper, Mark TI Mapping-based temporal pattern mining algorithm (MTPMA) identifies unique clusters of phosphopeptides regulated by vasopressin in collecting duct SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Saeed, Fahad; Hoffert, Jason; Pisitkun, Trairak; Knepper, Mark] NIH, Epithelial Syst Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406497 ER PT J AU Saito, K Moore, R Kamino, H Negishi, M AF Saito, Kosuke Moore, Rick Kamino, Hiroki Negishi, Masahiko TI The K+ Channel KCNK1: CAR-mediated Gene Regulation of Male-specific Induction by PB and Hepatic Hypertrophy SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Saito, Kosuke; Moore, Rick; Kamino, Hiroki; Negishi, Masahiko] NIEHS, LRDT, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708401198 ER PT J AU Sanchez-Lemus, E Benicky, J Saavedra, JM AF Sanchez-Lemus, Enrique Benicky, Julius Saavedra, Juan M. TI The Angiotensin II AT(1) receptor blockade inhibits the lipopolysaccharide-induced inflammatory response in the nucleus tractus solitarii (NTS) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Sanchez-Lemus, Enrique; Benicky, Julius; Saavedra, Juan M.] NIMH, Pharmacol Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708403925 ER PT J AU Sandoval, P Slentz, D Pisitkun, T Yu, M Miller, R Hoffert, J Knepper, M AF Sandoval, P. Slentz, D. Pisitkun, T. Yu, M. Miller, R. Hoffert, J. Knepper, M. TI LC-MS/MS-based large-scale profiling of protein half lives in renal collecting duct cells reveals that vasopressin increases half-life of aquaporin-2 protein SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Sandoval, P.; Slentz, D.; Pisitkun, T.; Yu, M.; Miller, R.; Hoffert, J.; Knepper, M.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708400529 ER PT J AU Sankavaram, K Chong, L Mah, E Bruno, RS Freake, HC AF Sankavaram, Kavitha Chong, Leelyn Mah, Eunice Bruno, Richard S. Freake, Hedley C. TI The Effects of Extracellular Zinc Depletion on Zinc Homeostasis and Oxidative Stress Responses in Cancer Cell Lines SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Sankavaram, Kavitha] NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA. [Chong, Leelyn; Mah, Eunice; Bruno, Richard S.; Freake, Hedley C.] Univ Connecticut, Storrs, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708401888 ER PT J AU Sarkar, C Chandra, G Zhang, ZJ Peng, SY Mukherjee, AB AF Sarkar, Chinmoy Chandra, Goutam Zhang, Zhongjian Peng, Shiyong Mukherjee, Anil B. TI Depletion of intracellular ceroids by N-t-butyl hydroxylamine: Therapeutic Implications for a neurodegenerative storage disorder, Infantile Neuronal Ceroid Lipofuscinosis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Sarkar, Chinmoy; Chandra, Goutam; Zhang, Zhongjian; Peng, Shiyong; Mukherjee, Anil B.] NICHD, Sect Dev Genet, PDEGEN, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708404579 ER PT J AU Schindler, CW Cogan, ES Thorndike, EB Panlilio, LV AF Schindler, Charles W. Cogan, Elizabeth S. Thorndike, Eric B. Panlilio, Leigh V. TI Effect of injection duration on the acquisition of cocaine self-administration in rats: the role of paired stimuli SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Schindler, Charles W.; Cogan, Elizabeth S.; Thorndike, Eric B.; Panlilio, Leigh V.] NIN NIDA Intramural Res, Behav Neurosci Preclin Pharmacol, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708403495 ER PT J AU Schu, DJ Gottesman, S AF Schu, Daniel Joseph Gottesman, Susan TI A study of covalently linked Hfqs and the requirements for RNA binding SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Schu, Daniel Joseph; Gottesman, Susan] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402627 ER PT J AU Schwefel, D Froehlich, C Eichhorst, J Wiesner, B Behlke, J Aravind, L Daumke, O AF Schwefel, David Froehlich, Chris Eichhorst, Jenny Wiesner, Burkhard Behlke, Joachim Aravind, L. Daumke, Oliver TI Structural Basis for Oligomerization in the Septin-like GTPase of Immunity-Associated Proteins 2 (GIMAP2) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Schwefel, David; Froehlich, Chris; Behlke, Joachim; Daumke, Oliver] Max Delbruck Ctr Mol Med, Berlin, Germany. [Eichhorst, Jenny; Wiesner, Burkhard] Leibniz Inst Mol Pharmacol, Berlin, Germany. [Aravind, L.] NIH, Computat Biol Branch, NCBI, NLM, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708404776 ER PT J AU Serafine, KM Rice, KC Riley, AL AF Serafine, Katherine Marie Rice, Kenner C. Riley, Anthony L. TI Effects of cross-drug preexposure on cocaine- and vanoxerine-induced conditioned taste aversions SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Serafine, Katherine Marie; Riley, Anthony L.] American Univ, Dept Psychol, Washington, DC 20016 USA. [Rice, Kenner C.] NIDA, Chem Biol Res Branch, Bethesda, MD 20892 USA. [Rice, Kenner C.] NIAAA, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708403503 ER PT J AU Shao, SC Hegde, RS AF Shao, Sichen Hegde, Ramanujan S. TI A novel pathway for the translocation of unusually small proteins SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Shao, Sichen; Hegde, Ramanujan S.] NIH, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. [Shao, Sichen] Johns Hopkins Univ, Dept Cellular Mol Dev Biol & Biophys, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708404510 ER PT J AU Sherman, E Barr, V Manley, S Patterson, G Balagopalan, L Akpan, I Regan, CK Lippincott-Schwartz, J Samelson, LE AF Sherman, Eilon Barr, Valarie Manley, Suliana Patterson, George Balagopalan, Lakshmi Akpan, Itoro Regan, Carole K. Lippincott-Schwartz, Jennifer Samelson, Lawrence E. TI Complex nano-scale organization and role of LAT signaling complexes resolved at the single molecule level SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Sherman, Eilon; Barr, Valarie; Balagopalan, Lakshmi; Akpan, Itoro; Regan, Carole K.; Samelson, Lawrence E.] NCI, LCMB, NIH, Bethesda, MD 20892 USA. [Manley, Suliana; Patterson, George; Lippincott-Schwartz, Jennifer] NICHD, Cell Biol & Metab Program, NIH, Bethesda, MD USA. RI Sherman, Eilon /B-3688-2014 OI Sherman, Eilon /0000-0002-7403-6036 NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402891 ER PT J AU Sidhu, VK Huang, B Kim, HY AF Sidhu, Vishaldeep K. Huang, Bill Kim, Hee-Yong TI Differential proteomic analysis of the brain synaptic plasma membrane proteins from DHA-deficient and adequate mice using 16O/18O labeling SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Sidhu, Vishaldeep K.; Huang, Bill; Kim, Hee-Yong] NIAAA, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406500 ER PT J AU Simpson, M Hoover, S Simpson, E Webster, J AF Simpson, Mark Hoover, Shelley Simpson, Eleanor Webster, Joshua TI Quantitative genetic-learning pattern recognition image analysis in cancer tissue biobank quality assurance SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Simpson, Mark; Hoover, Shelley; Webster, Joshua] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. [Simpson, Eleanor] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708405310 ER PT J AU Smith, W Ainsztein, A Basavappa, R Chin, J Edmonds, C Flicker, P Preusch, P Wehrle, J Lewis, C Berg, J AF Smith, Ward Ainsztein, Alexandra Basavappa, Ravi Chin, Jean Edmonds, Charles Flicker, Paula Preusch, Peter Wehrle, Janna Lewis, Catherine Berg, Jeremy TI NIGMS PSI: Biology Initiative - Enabling High-Throughput Structural Biology and Structural Genomics SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Smith, Ward; Ainsztein, Alexandra; Basavappa, Ravi; Chin, Jean; Edmonds, Charles; Flicker, Paula; Preusch, Peter; Wehrle, Janna; Lewis, Catherine; Berg, Jeremy] NIGMS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402763 ER PT J AU Steck, SE Su, LJ Arab, L Fontham, ETH Bensen, J Hebert, JR Zhang, HM Mohler, J AF Steck, Susan E. Su, L. Joseph Arab, Lenore Fontham, Elizabeth T. H. Bensen, Jeannette Hebert, James R. Zhang, Hongmei Mohler, James TI Intake of dairy and calcium, NSAIDs and prostate cancer aggressiveness SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Steck, Susan E.; Hebert, James R.; Zhang, Hongmei] Univ S Carolina, Columbia, SC 29208 USA. [Su, L. Joseph] NCI, Div Canc Prevent & Populat Sci, Rockville, MD USA. [Arab, Lenore] Univ Calif Los Angeles, Los Angeles, CA USA. [Fontham, Elizabeth T. H.] LSUHSC, Sch Publ Hlth, New Orleans, LA USA. [Bensen, Jeannette] Univ N Carolina, Chapel Hill, NC USA. [Mohler, James] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708401807 ER PT J AU Stevens, MV Kim, KY Springer, D Anderson, S Noguchi, A Esfahani, S Daniels, M Shen, J San, H Sack, MN AF Stevens, Mark Vincent Kim, Kye-Young Springer, Danielle Anderson, Stasia Noguchi, Audrey Esfahani, Shervin Daniels, Mathew Shen, Jie San, Hong Sack, Michael N. TI Cardiac function in response to pressure-overload and aging-induced stress involves regulation of mitochondrial dynamics by the mitochondrial kinase, Pink1 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Stevens, Mark Vincent; Kim, Kye-Young; Springer, Danielle; Anderson, Stasia; Noguchi, Audrey; Esfahani, Shervin; Daniels, Mathew; San, Hong; Sack, Michael N.] NHLBI, NIH, Bethesda, MD 20892 USA. [Springer, Danielle; Noguchi, Audrey] NIH, Mouse Phenotyping Core, Bethesda, MD 20892 USA. [Anderson, Stasia] NIH, Mouse Imaging Facil, Bethesda, MD 20892 USA. [Esfahani, Shervin; Daniels, Mathew] NIH, Electron Microscopy Core, Bethesda, MD 20892 USA. [Shen, Jie] Harvard Univ, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708404635 ER PT J AU Subramanian, P Locatelli-Hoops, S Notari, L Becerra, SP AF Subramanian, Preeti Locatelli-Hoops, Silvia Notari, Luigi Becerra, S. Patricia TI Structure-function relationships of pigment epithelium-derived factor receptor (PEDF-R): Identification of a PEDF binding region SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Subramanian, Preeti; Locatelli-Hoops, Silvia; Notari, Luigi; Becerra, S. Patricia] NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406527 ER PT J AU Sueyoshi, T Green, WD Vinal, K Woodrum, TS Moore, R Negishi, M AF Sueyoshi, Tatsuya Green, William D. Vinal, Kellie Woodrum, Tyler S. Moore, Rick Negishi, Masahiko TI Garlic Extract Diallyl Sulfide (DAS) Activates Nuclear Receptor CAR to Induce the Sult1e1 Gene in Mouse Liver SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Sueyoshi, Tatsuya; Green, William D.; Vinal, Kellie; Woodrum, Tyler S.; Moore, Rick; Negishi, Masahiko] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708400155 ER PT J AU Sun, JH Murphy, E AF Sun, Junhui Murphy, Elizabeth TI Methyl-beta-cyclodextrin (M beta CD) treatment abolished ischemic preconditioning (IPC)-induced cardioprotection and increase of protein S-nitrosylation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Sun, Junhui; Murphy, Elizabeth] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708400427 ER PT J AU Taha, AY Cheon, Y Modi, HR Ramadan, E Basselin, M Rapoport, SI AF Taha, Ameer Y. Cheon, Yewon Modi, Hiren R. Ramadan, Epolia Basselin, Mireille Rapoport, Stanley I. TI Disturbed brain arachidonic acid metabolism in HIV-1 transgenic rats SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Taha, Ameer Y.; Cheon, Yewon; Modi, Hiren R.; Ramadan, Epolia; Basselin, Mireille; Rapoport, Stanley I.] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708400691 ER PT J AU Tang, WK Li, CC Xia, D AF Tang, Wai Kwan Li, Chou-Chi Xia, Di TI A novel ATP dependent conformational change of p97 ND1 fragment revealed by crystal structures of disease related mutants SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Tang, Wai Kwan; Xia, Di] NIH, Bethesda, MD 20892 USA. [Li, Chou-Chi] NIH, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406401 ER PT J AU Tauseef, M Vogel, S Dietrich, A Malik, A Birnbaumer, L Mehta, D AF Tauseef, Mohammad Vogel, Steven Dietrich, Alexander Malik, Asrar Birnbaumer, Lutz Mehta, Dolly TI Tyrosine phosphorylation of STIM1 induced by TRPC6-Pyk2 cascade regulates store-operated calcium entry and endothelial permeability SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Tauseef, Mohammad; Vogel, Steven; Malik, Asrar; Mehta, Dolly] Univ Illinois, Chicago, IL USA. [Dietrich, Alexander] Univ Marburg, Marburg, Germany. [Birnbaumer, Lutz] NIEHS, Res Triangle Pk, NC 27709 USA. RI Dietrich, Alexander/G-8619-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708401109 ER PT J AU Temiz, NA Donohue, DE Bacolla, A Vasquez, K Luke, BT Collins, JR AF Temiz, Nuri Alpay Donohue, Duncan E. Bacolla, Albino Vasquez, Karen Luke, Brian T. Collins, Jack R. TI Effects of cytosine C5 methylation on DNA stability and dynamics SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Temiz, Nuri Alpay; Donohue, Duncan E.; Luke, Brian T.; Collins, Jack R.] NCI, Adv Biomed Comp Ctr, SAIC Frederick, Frederick, MD 21701 USA. [Bacolla, Albino; Vasquez, Karen] Univ Texas MD Anderson Canc Ctr, Dept Mol Carcinogenesis, Smithville, TX USA. RI Bacolla, Albino/N-3877-2013 OI Bacolla, Albino/0000-0003-0206-8423 NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708404416 ER PT J AU Tesikova, M Dezitter, X Klokk, TI Kirli, Z Hager, GL Saatcioglu, F AF Tesikova, Martina Dezitter, Xavier Klokk, Tove I. Kirli, Zeynep Hager, Gordon L. Saatcioglu, Fahri TI Differential effects of histone deacetylase inhibitors on transcription factor dynamics and activity at the same response element SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Tesikova, Martina; Dezitter, Xavier; Klokk, Tove I.; Kirli, Zeynep; Saatcioglu, Fahri] Inst Mol Biol, Dept Mol Biosci, Oslo, Norway. [Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708401200 ER PT J AU Tiffany, TMN Stevens, M Wong, R Sack, M Murphy, E AF Tiffany Tuyen Minh Nguyen Stevens, Mark Wong, Renee Sack, Michael Murphy, Elizabeth TI Modulation of mitochondrial permeability transition pore by the F(1)Fo ATP synthase O subunit SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Tiffany Tuyen Minh Nguyen; Wong, Renee; Murphy, Elizabeth] NHLBI, Biol Syst Ctr, Bethesda, MD 20892 USA. [Stevens, Mark; Sack, Michael] NHLBI, Mol Med Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708401296 ER PT J AU Tiffany, TMN Stevens, M Kohr, M Steenbergen, C Sack, M Murphy, E AF Tiffany Tuyen Minh Nguyen Stevens, Mark Kohr, Mark Steenbergen, Charles Sack, Michael Murphy, Elizabeth TI S-nitrosylation of cyclophilin D alters mitochondrial permeability transition pore SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Tiffany Tuyen Minh Nguyen; Murphy, Elizabeth] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA. [Stevens, Mark; Sack, Michael] NHLBI, Mol Med Branch, NIH, Bethesda, MD 20892 USA. [Kohr, Mark; Steenbergen, Charles] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708400411 ER PT J AU Tiso, M Tejero, J Basu, S Azarov, I Wang, XD Simplaceanu, V Frizzell, S Jayaraman, T Geary, L Shapiro, C Ho, C Shiva, S Kim-Shapiro, DB Gladwin, MT AF Tiso, Mauro Tejero, Jesus Basu, Swati Azarov, Ivan Wang, Xunde Simplaceanu, Virgil Frizzell, Sheila Jayaraman, Thottala Geary, Lisa Shapiro, Calli Ho, Chien Shiva, Sruti Kim-Shapiro, Daniel B. Gladwin, Mark T. TI HUMAN NEUROGLOBIN FUNCTIONS AS A REDOX REGULATED NITRITE REDUCTASE SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Tiso, Mauro; Tejero, Jesus; Frizzell, Sheila; Jayaraman, Thottala; Geary, Lisa; Shapiro, Calli; Shiva, Sruti; Gladwin, Mark T.] Univ Pittsburgh, Vasc Med Inst, Pittsburgh, PA USA. [Tiso, Mauro] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. [Basu, Swati; Azarov, Ivan; Kim-Shapiro, Daniel B.] Wake Forest Univ, Dept Phys, Winston Salem, NC 27109 USA. [Wang, Xunde] NHLBI, NIH, Bethesda, MD 20892 USA. [Simplaceanu, Virgil; Ho, Chien] Carnegie Mellon Univ, Dept Biol Sci, Pittsburgh, PA 15213 USA. RI Ho, Chien/O-6112-2016 OI Ho, Chien/0000-0002-4094-9232 NR 0 TC 0 Z9 0 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406718 ER PT J AU Tobe, R Yoo, MH Fradejas-Villar, N Carlson, BA Calvo, S Gladyshev, VN Hatfield, DL AF Tobe, Ryuta Yoo, Min-Hyuk Fradejas-Villar, Noelia Carlson, Bradley A. Calvo, Soledad Gladyshev, Vadim N. Hatfield, Dolph L. TI Increased sodium selenite cytotoxicity in thioredoxin reductase 1 knockdown cancer cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Tobe, Ryuta; Yoo, Min-Hyuk; Carlson, Bradley A.; Hatfield, Dolph L.] NCI, MBSS, LCP, NIH, Bethesda, MD 20892 USA. [Fradejas-Villar, Noelia; Calvo, Soledad] Univ Castilla La Mancha, Dept Med Sci, Albacete, Spain. [Fradejas-Villar, Noelia; Calvo, Soledad] Univ Castilla La Mancha, Res Inst Neurol Incapac, Albacete, Spain. [Gladyshev, Vadim N.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RI Gladyshev, Vadim/A-9894-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708401342 ER PT J AU Topanurak, S Ferraris, JD Li, JX Williams, CK Burg, MB AF Topanurak, Supachai Ferraris, Joan D. Li, Jinxi Williams, Chester K. Burg, Maurice B. TI Mechanism of high NaCl- and urea-induced inhibition of GDPD5, an enzyme whose phosphodiesterase activity breaks down the osmoprotective organic osmolyte glycerophosphocholine SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Topanurak, Supachai; Ferraris, Joan D.; Li, Jinxi; Williams, Chester K.; Burg, Maurice B.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708404018 ER PT J AU Trotter, KW Archer, TK AF Trotter, Kevin W. Archer, Trevor K. TI Direct interaction between Ku70/86 and BRG1 are required for nuclear receptor-dependent transcriptional activation in vivo SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Trotter, Kevin W.; Archer, Trevor K.] NIEHS, LMC, NIH, Druham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406338 ER PT J AU Tseng, M Graubard, BI Ziegler, R AF Tseng, Marilyn Graubard, Barry I. Ziegler, Regina TI Dietary patterns predict mortality in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) cohort SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Tseng, Marilyn] Calif Polytech State Univ San Luis Obispo, Dept Kinesiol, San Luis Obispo, CA 93407 USA. [Graubard, Barry I.; Ziegler, Regina] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 5 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402125 ER PT J AU Tsuji, PA Carlson, BA Yoo, MH Xu, XM Naranjo-Suarez, S Fomenko, D Hatfield, DL Gladyshev, VN Davis, CD AF Tsuji, Petra A. Carlson, Bradley A. Yoo, Min-Hyuk Xu, Xue-Ming Naranjo-Suarez, Salvador Fomenko, Dmitri Hatfield, Dolph L. Gladyshev, Vadim N. Davis, Cindy D. TI Sep15 knockout in mice provides protection against chemically-induced aberrant crypt formation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Tsuji, Petra A.; Carlson, Bradley A.; Yoo, Min-Hyuk; Xu, Xue-Ming; Naranjo-Suarez, Salvador; Hatfield, Dolph L.] NCI, MBSS LCP, Bethesda, MD 20892 USA. [Tsuji, Petra A.] NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. [Fomenko, Dmitri] Univ Nebraska, Biochem & Redox Biol Ctr, Lincoln, NE USA. [Gladyshev, Vadim N.] Harvard Univ, Sch Med, Boston, MA USA. [Davis, Cindy D.] NCI, Canc Prevent Div, Rockville, MD USA. RI Gladyshev, Vadim/A-9894-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708401337 ER PT J AU Tuo, JS Cao, XG Shen, DF Wang, YJ Oh, JY Prockop, DJ Chan, CC AF Tuo, Jingsheng Cao, Xiaoguang Shen, Defen Wang, Yujuan Oh, Joo-Youn Prockop, Darwin J. Chan, Chi-Chao TI The effect of intravitreous administration of recombinant TSG-6 protein on the retinal lesion in Ccl2-/-/Cx3cr1-/- mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Tuo, Jingsheng; Cao, Xiaoguang; Shen, Defen; Wang, Yujuan; Prockop, Darwin J.; Chan, Chi-Chao] Nationla Eye Inst, Lab Immunol, Bethesda, MD USA. [Oh, Joo-Youn] Coll Med Scott & White, Texas A&M Hlth Sci Ctr, Temple, TX USA. RI wang, yujuan/C-8428-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708405472 ER PT J AU Upadhyay, G Yin, YZ Yuan, HY Kopelovich, L Derynck, R Glazer, RI AF Upadhyay, Geeta Yin, Yuzhi Yuan, Hongyan Kopelovich, Levy Derynck, Rik Glazer, Robert I. TI Stem cell antigen-1 (Sca-1) disrupts GDF10/TGF-beta signal transduction at the plasma membrane to regulate Smad2/3 nuclear signaling SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Upadhyay, Geeta; Yin, Yuzhi; Yuan, Hongyan; Glazer, Robert I.] Georgetown Univ, Washington, DC USA. [Kopelovich, Levy] NCI, Chemoprevent Branch, Bethesda, MD 20892 USA. [Derynck, Rik] UCSF, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708401962 ER PT J AU Volkow, ND Wang, GJ Fowler, JS Telang, F Tomasi, D AF Volkow, Nora D. Wang, Gene-Jack Fowler, Joanna S. Telang, Frank Tomasi, Dardo TI Overlapping Neuronal Circuits in Addiction and Obesity SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Volkow, Nora D.] NIDA, Bethesda, MD 20892 USA. [Wang, Gene-Jack; Fowler, Joanna S.] Brookhaven Natl Lab, Upton, NY 11973 USA. [Telang, Frank; Tomasi, Dardo] NIAAA, Lab Neuroimaging, Bethesda, MD USA. RI Tomasi, Dardo/J-2127-2015 NR 0 TC 0 Z9 0 U1 0 U2 6 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708404513 ER PT J AU Wang, PM Martin, WJ AF Wang, Ping Ming Martin, William J., II TI A new approach to clearly identify collagen fibers/fibrils and inflammatory cells from H&E stained murine lung sections using fluorescent microscopy SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Wang, Ping Ming; Martin, William J., II] NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708403785 ER PT J AU Wang, R Ferraris, JD Wang, GH Gucek, M Burg, MB AF Wang, Rong Ferraris, Joan D. Wang, Guanghui Gucek, Marjan Burg, Maurice B. TI Phosphoproteome profiling of HEK 293 cells under osmotic stress using SILAC SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Wang, Rong; Ferraris, Joan D.; Wang, Guanghui; Gucek, Marjan; Burg, Maurice B.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402759 ER PT J AU Wang, RH Xu, XL Deng, CX AF Wang, Rui-Hong Xu, Xiaoling Deng, Chuxia TI SIRT1 Is Critical for Pdx1 Transcription and beta-Cell Formation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Wang, Rui-Hong; Xu, Xiaoling] NIDDK, GDDB, Bethesda, MD USA. [Deng, Chuxia] NIDDK, GDDK, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708404572 ER PT J AU Wang, T Milner, J Kim, YS AF Wang, Thomas Milner, John Kim, Young S. TI Differential effects of broccoli-derived phytochemicals indole-3-carbinol and its dimer 3, 3 '-diindolylmethane on liver X receptor-responsive genes in human prostate cancer cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Wang, Thomas] USDA, DGIL, BHNRC, Beltsville, MD 20705 USA. [Milner, John; Kim, Young S.] NCI, NSRG, DCP, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406922 ER PT J AU Wang, VM Rosen, R Meyerle, C Kurup, S Chew, E Chan, CC Tuo, JS AF Wang, Vinson Matthew Rosen, Richard Meyerle, Catherine Kurup, Shree Chew, Emily Chan, Chi-Chao Tuo, Jingsheng TI Polymorphic variations affecting response to anti-VEGF therapy in patients with exudative age-related macular degeneration SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Wang, Vinson Matthew; Chan, Chi-Chao; Tuo, Jingsheng] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Meyerle, Catherine; Chew, Emily] NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. [Rosen, Richard] New York Eye & Ear Infirm, New York, NY 10003 USA. [Kurup, Shree] Wake Forest Univ, Ctr Eye, Dept Ophthalmol, Winston Salem, NC 27109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406766 ER PT J AU Wang, YJ Cao, XG Shen, DF Tuo, JS Villasmil, R Chan, CC AF Wang, Yujuan Cao, Xiaoguang Shen, Defen Tuo, Jingsheng Villasmil, Rafael Chan, Chi-Chao TI Up-regulation of apoptosis in Ccl2-/-/Cx3cr1-/-retinal pigment epithelial cells under inflammatory and oxidative stress SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Wang, Yujuan; Cao, Xiaoguang; Shen, Defen; Tuo, Jingsheng; Chan, Chi-Chao] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Villasmil, Rafael] NEI, Flow Cytometry Core Facil, NIH, Bethesda, MD 20892 USA. [Wang, Yujuan] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, Guangzhou, Guangdong, Peoples R China. [Cao, Xiaoguang] Peking Univ, Peoples Hosp, Dept Ophthalmol, Beijing 100871, Peoples R China. RI wang, yujuan/C-8428-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402254 ER PT J AU Webster, JD Hoover, SB Juopperi, T Edwards, JB Simpson, RM AF Webster, Joshua David Hoover, Shelley B. Juopperi, Tarja Edwards, Jennifer B. Simpson, R. Mark TI Characterization of stem cell-derived teratomas from immunodeficient mice using histologic pattern recognition software SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Webster, Joshua David; Hoover, Shelley B.; Edwards, Jennifer B.; Simpson, R. Mark] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. [Juopperi, Tarja] Johns Hopkins Univ, Inst Cell Engn, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708405270 ER PT J AU Weinstein, SJ Yu, K Horst, RL Parisi, D Virtamo, J Albanes, D AF Weinstein, Stephanie J. Yu, Kai Horst, Ronald L. Parisi, Dominick Virtamo, Jarmo Albanes, Demetrius TI Serum 25-hydroxyvitamin D and lung cancer risk SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Weinstein, Stephanie J.; Yu, Kai; Albanes, Demetrius] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Horst, Ronald L.] Heartland Assays Inc, Ames, IA USA. [Parisi, Dominick] IMS Inc, Silver Spring, MD USA. [Virtamo, Jarmo] Natl Inst Hlth & Welf, Helsinki, Finland. RI Albanes, Demetrius/B-9749-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708401808 ER PT J AU Wolff, EC Lee, SB Park, JH Park, MH AF Wolff, Edith C. Lee, Seung Bum Park, Jong Hwan Park, Myung Hee TI Inactivation of eukaryotic initiation factor 5A (eIF5A) by specific acetylation of its hypusine residue by spermidine/spermine acetyltransferase 1 (SSAT1) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Wolff, Edith C.; Lee, Seung Bum; Park, Jong Hwan; Park, Myung Hee] NIDCR, OPCB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402657 ER PT J AU Wu, LM Ma, CA Jain, A AF Wu, Liming Ma, Chi A. Jain, Ashish TI Aurora B interacts with NIR-p53, leading to p53 phosphorylation in its DNA-binding domain and subsequent functional suppression SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Wu, Liming; Ma, Chi A.; Jain, Ashish] NIAID, LHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402607 ER PT J AU Yadav, H Gavrilova, O Lonning, S Rane, SG AF Yadav, Hariom Gavrilova, Oksana Lonning, Scott Rane, Sushil G. TI TGF-beta/SMAD3 SIGNALING REGULATES HEPATIC GLUCOSE METABOLISM SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Yadav, Hariom; Rane, Sushil G.] NIDDK, NIH, Bethesda, MD USA. [Gavrilova, Oksana] NIDDK, NIDDK Mouse Metab Core, Bethesda, MD USA. [Lonning, Scott] Genzyme, Immunotherapy, Framingham, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708401574 ER PT J AU Yang, J Xie, XT Anderson, DE Stenkula, KG Yver, D Meyer, C Cushman, SW AF Yang, Jian Xie, Xitao Anderson, D. Eric Stenkula, Karin G. Yver, Dena Meyer, Christian Cushman, Samuel W. TI Identification of new molecular components in the GLUT4 clusters in the plasma membrane of adipose cells by mass spectrometry-based proteomics SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Yang, Jian; Stenkula, Karin G.; Yver, Dena; Cushman, Samuel W.] NIDDK, EDMNS, Diabet Branch, NIH, Bethesda, MD USA. [Anderson, D. Eric] NIDDK, Adv Mass Spectrometry Facil, NIH, Bethesda, MD USA. [Yang, Jian] Univ S Alabama, Coll Med, Dept Physiol, Mobile, AL 36688 USA. [Xie, Xitao; Meyer, Christian] Arizona State Univ, Ctr Metab Biol, Tempe, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402747 ER PT J AU Yanpallewar, S Fernandes, K Marathe, S Vadodaria, K Jhaveri, D Rommelfanger, K Ladiwala, U Jha, S Muthig, V Hein, L Bartlett, P Weinshenker, D Vaidya, V AF Yanpallewar, Sudhirkumar Fernandes, Kimberly Marathe, Swananda Vadodaria, Krishna Jhaveri, Dhanisha Rommelfanger, Karen Ladiwala, Uma Jha, Shanker Muthig, Verena Hein, Lutz Bartlett, Perry Weinshenker, David Vaidya, Vidita TI Alpha2-Adrenoceptor Blockade Accelerates the Neurogenic, Neurotrophic, and Behavioral Effects of Chronic Antidepressant Treatment SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Yanpallewar, Sudhirkumar; Fernandes, Kimberly; Marathe, Swananda; Vadodaria, Krishna; Ladiwala, Uma; Jha, Shanker; Vaidya, Vidita] Tata Inst Fundamental Res, Dept Biol Sci, Bombay 400005, Maharashtra, India. [Yanpallewar, Sudhirkumar] NCI, Mouse Canc Genet Program, Frederick, MD 21701 USA. [Jhaveri, Dhanisha; Bartlett, Perry] Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia. [Rommelfanger, Karen; Weinshenker, David] Emory Univ, Dept Human Genet, Atlanta, GA 30322 USA. [Muthig, Verena; Hein, Lutz] Univ Freiburg, Dept Expt & Clin Pharmacol & Toxicol, D-79106 Freiburg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708400077 ER PT J AU Yazawa, I O'Donovan, M AF Yazawa, Itaru O'Donovan, Michael TI The mechanism(s) of increasing respiratory rate during locomotor-like activity SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Yazawa, Itaru; O'Donovan, Michael] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406069 ER PT J AU Ye, YH AF Ye, Yihong TI The role of the p97 ATPase in protein quality control at the endoplasmic reticulum SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Ye, Yihong] NIH, Mol Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402078 ER PT J AU Yedavalli, V Jeang, KT AF Yedavalli, Venkat Jeang, Kuan-Teh TI The nuclear matrix protein, Matrin 3 is required export of HIV-1 unspliced/partially spliced RNAs SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Yedavalli, Venkat; Jeang, Kuan-Teh] NIH, Mol Microbiol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406328 ER PT J AU Yoo, KW Chitnis, A AF Yoo, Kyeong-Won Chitnis, Ajay TI Prox1 Influences Neuromast Deposition Frequency and Proliferation in the migrating Posterior Lateral Line Primordium SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Yoo, Kyeong-Won; Chitnis, Ajay] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402453 ER PT J AU Zane, LK Yasunaga, J Melo, GEBA Jeang, KT AF Zane, Linda Karine Yasunaga, Junichiro Melo, Gustavo Eustaquio Brito Alvim Jeang, Kuan-Teh TI Transformation of human embryonic stem cells by HTLV-1 Tax SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Zane, Linda Karine; Yasunaga, Junichiro; Melo, Gustavo Eustaquio Brito Alvim; Jeang, Kuan-Teh] NIAID, LMM, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708404409 ER PT J AU Zhang, JH Pandey, M Panicker, LM Seigneur, EM Koo, L Schwartz, OM Chen, CKJ Simonds, WF AF Zhang, Jianhua Pandey, Mritunjay Panicker, Leelamma M. Seigneur, Erica M. Koo, Lily Schwartz, Owen M. Chen, Ching-Kang Jason Simonds, William F. TI Lack of heterotrimeric G protein beta 5 impairs brain development and neurologic function in mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Zhang, Jianhua; Pandey, Mritunjay; Panicker, Leelamma M.; Seigneur, Erica M.; Schwartz, Owen M.; Simonds, William F.] NIDDK, NIH, Bethesda, MD USA. [Koo, Lily] NIAID, NIH, Bethesda, MD 20892 USA. [Schwartz, Owen M.; Chen, Ching-Kang Jason] Virginia Commonwealth Univ, Dept Biochem & Mol Biol, Richmond, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708403918 ER PT J AU Zhang, J Tuo, JS Cao, XG Shen, DF Li, W Chan, CC AF Zhang, Jun Tuo, Jingsheng Cao, Xiaoguang Shen, Defen Li, Wei Chan, Chi-Chao TI Synaptic pathology of outer retina in Ccl2/Cx3cr1 deficient mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Zhang, Jun] NEI, Histol Core, NIH, Bethesda, MD 20892 USA. [Tuo, Jingsheng; Cao, Xiaoguang; Shen, Defen; Chan, Chi-Chao] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Li, Wei] NEI, Unit Retinal Neurophysiol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708400045 ER PT J AU Zhang, SY Surapureddi, S Goldstein, JA AF Zhang, Shuyun Surapureddi, Sailesh Goldstein, Joyce A. TI MicroRNAs 103 and 107 regulate the expression of Human Cytochrome P450 2C8 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Zhang, Shuyun; Surapureddi, Sailesh; Goldstein, Joyce A.] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708400154 ER PT J AU Zhao, B Pisitkun, T Hoffert, J Chou, CL Knepper, M AF Zhao, B. Pisitkun, T. Hoffert, J. Chou, C. L. Knepper, M. TI Large-scale phosphoproteomic profiling of native rat renal collecting duct epithelium: Tyrosine phosphorylation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Zhao, B.; Pisitkun, T.; Hoffert, J.; Chou, C. L.; Knepper, M.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406494 ER PT J AU Zhao, CW Roseland, J Andrews, K Holden, J Middleton, A Dwyer, J Bailey, R Saldanha, L AF Zhao, Cuiwei Roseland, Janet Andrews, Karen Holden, Joanne Middleton, Angela Dwyer, Johanna Bailey, Regan Saldanha, Leila TI The Dietary Supplement Ingredient Database (DSID): Labeled nutrient distribution in children's multivitamin/mineral (MVM) products SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Zhao, Cuiwei; Roseland, Janet; Andrews, Karen; Holden, Joanne; Middleton, Angela] ARS, BHNRC, USDA, Nutrient Data Lab, Beltsville, MD USA. [Dwyer, Johanna; Bailey, Regan; Saldanha, Leila] NIH, Off Dietary Supplement, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708403299 ER PT J AU Zhao, H Sun, JH Deschamps, AM Kim, G Murphy, E Levine, RL AF Zhao, Hang Sun, Junhui Deschamps, Anne M. Kim, Geumsoo Murphy, Elizabeth Levine, Rodney L. TI Overexpression of myristoylated methionine sulfoxide reductase A in the mouse protects the heart against ischemia-reperfusion injury SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Zhao, Hang; Kim, Geumsoo; Levine, Rodney L.] NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. [Sun, Junhui; Deschamps, Anne M.; Murphy, Elizabeth] NHLBI, Lab Cardiac Physiol, NIH, Bethesda, MD 20892 USA. RI Levine, Rodney/D-9885-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406425 ER PT J AU Zhou, XM Burg, MB Ferraris, JD AF Zhou, Xiaoming Burg, Maurice B. Ferraris, Joan D. TI Rac1/OSM and PLC-gamma1 contribute in combination to high NaCl-induced activation of the osmoprotective transcription factor TonEBP/OREBP SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Zhou, Xiaoming] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Burg, Maurice B.; Ferraris, Joan D.] NHLBI, LKEM, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708404019 ER PT J AU Bennett, SN Caporaso, N Fitzpatrick, AL Agrawal, A Barnes, K Boyd, HA Cornelis, MC Hansel, NN Heiss, G Heit, JA Kang, JH Kittner, SJ Kraft, P Lowe, W Marazita, ML Monroe, KR Pasquale, LR Ramos, EM van Dam, RM Udren, J Williams, K AF Bennett, Siiri N. Caporaso, Neil Fitzpatrick, Annette L. Agrawal, Arpana Barnes, Kathleen Boyd, Heather A. Cornelis, Marilyn C. Hansel, Nadia N. Heiss, Gerardo Heit, John A. Kang, Jae Hee Kittner, Steven J. Kraft, Peter Lowe, William Marazita, Mary L. Monroe, Kristine R. Pasquale, Louis R. Ramos, Erin M. van Dam, Rob M. Udren, Jenna Williams, Kayleen CA GENEVA Consortium TI Phenotype Harmonization and Cross-Study Collaboration in GWAS Consortia: The GENEVA Experience SO GENETIC EPIDEMIOLOGY LA English DT Article DE phenotype; harmonization; genome-wide association studies; GENEVA; consortia ID GENOME-WIDE ASSOCIATION; OPEN-ANGLE GLAUCOMA; GENETIC-ASSOCIATION; ENVIRONMENT INTERACTIONS; GENOTYPE IMPUTATION; EPIDEMIOLOGY; METAANALYSIS; VARIANTS; TRAITS; RISK AB Genome-wide association study (GWAS) consortia and collaborations formed to detect genetic loci for common phenotypes or investigate gene-environment (G*E) interactions are increasingly common. While these consortia effectively increase sample size, phenotype heterogeneity across studies represents a major obstacle that limits successful identification of these associations. Investigators are faced with the challenge of how to harmonize previously collected phenotype data obtained using different data collection instruments which cover topics in varying degrees of detail and over diverse time frames. This process has not been described in detail. We describe here some of the strategies and pitfalls associated with combining phenotype data from varying studies. Using the Gene Environment Association Studies (GENEVA) multi-site GWAS consortium as an example, this paper provides an illustration to guide GWAS consortia through the process of phenotype harmonization and describes key issues that arise when sharing data across disparate studies. GENEVA is unusual in the diversity of disease endpoints and so the issues it faces as its participating studies share data will be informative for many collaborations. Phenotype harmonization requires identifying common phenotypes, determining the feasibility of cross-study analysis for each, preparing common definitions, and applying appropriate algorithms. Other issues to be considered include genotyping timeframes, coordination of parallel efforts by other collaborative groups, analytic approaches, and imputation of genotype data. GENEVA's harmonization efforts and policy of promoting data sharing and collaboration, not only within GENEVA but also with outside collaborations, can provide important guidance to ongoing and new consortia. Genet. Epidemiol. 35:159-173, 2011. (c) 2011 Wiley-Liss, Inc. C1 [Bennett, Siiri N.; Fitzpatrick, Annette L.; Udren, Jenna; Williams, Kayleen] Univ Washington, Dept Biostat, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98115 USA. [Caporaso, Neil] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Fitzpatrick, Annette L.] Univ Washington, Dept Epidemiol, Seattle, WA 98115 USA. [Agrawal, Arpana] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 98115 USA. [Barnes, Kathleen; Hansel, Nadia N.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Boyd, Heather A.] Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark. [Heiss, Gerardo] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. [Heit, John A.] Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA. [Kang, Jae Hee; Pasquale, Louis R.] Harvard Univ, Sch Med, Boston, MA USA. [Kittner, Steven J.] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. [Kittner, Steven J.] Baltimore Vet Affairs Med Ctr, Baltimore, MD 21201 USA. [Kraft, Peter] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Lowe, William] Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Marazita, Mary L.] Univ Pittsburgh, Sch Dent Med, Dept Oral Biol, Ctr Craniofacial & Dent Genet, Pittsburgh, PA USA. [Marazita, Mary L.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA. [Marazita, Mary L.] Univ Pittsburgh, Clin & Translat Sci Inst, Pittsburgh, PA 15261 USA. [Marazita, Mary L.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15261 USA. [Monroe, Kristine R.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Ramos, Erin M.] NHGRI, Off Populat Genom, NIH, Bethesda, MD 20892 USA. [van Dam, Rob M.] Natl Univ Singapore, Fac Med, Dept Epidemiol & Publ Hlth & Med, Singapore 117548, Singapore. [van Dam, Rob M.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Bennett, SN (reprint author), Univ Washington, Dept Biostat, Collaborat Hlth Studies Coordinating Ctr, Bldg 29,Suite 310,6200 NE 74th St, Seattle, WA 98115 USA. EM siirib@u.washington.edu RI van Dam, Rob/F-9674-2010 OI van Dam, Rob/0000-0002-7354-8734 FU NIH Genes, Environment and Health Initiative; NIH [U01HG004738, Z01CP010200, U01HG04424, U01HG004438, HHSN268200782096C, HHSN268200625226C, U01HG004402, U01HG004446, U01HG004735, U01HG004728, U01HG004423, U01HG004436, U01HG004415, U01HG004726, U01HG004399, U01HG004729, U01HG004422]; NIDCR [U01DE018993, U01DE018903]; NIAAA [U10AA008401]; NIDA [P01CA089392, R01DA013423]; NHLBI [N01HC55015, N01HC55016, N01HC55018, N01HC55019, N01HC-55020, N01HC-55021, N01HC55022, R01HL087641, R01HL59367, R01HL086694]; NIH Roadmap for Medical Research [UL1RR025005]; NCI [CA63464, CA54281, CA136792]; NINDS; Office for Research in Women's Health [R01NS45012]; NEI [R01EY015473, R01EY015872] FX Contract grant sponsors: NIH Genes, Environment and Health Initiative; NIH; Contract grant numbers: U01HG004738; Z01CP010200; U01HG04424; U01HG004438; HHSN268200782096C; HHSN268200625226C; U01HG004402; U01HG004446; U01HG004735; U01HG004728; U01HG004423; U01HG004436; U01HG004415; U01HG004726; U01HG004399; U01HG004729; U01HG004422; Contract grant sponsor: NIDCR; Contract grant numbers: U01DE018993; U01DE018903; Contract grant sponsor: NIAAA; Contract grant number: U10AA008401; Contract grant sponsor: NIDA; Contract grant numbers: P01CA089392; R01DA013423; Contract grant sponsor: NHLBI; Contract grant numbers: N01HC55015; N01HC55016; N01HC55018; N01HC55019; N01HC-55020; N01HC-55021; N01HC55022; R01HL087641; R01HL59367; R01HL086694; Contract grant sponsor: NIH Roadmap for Medical Research; Contract grant number: UL1RR025005; Contract grant sponsor: NCI; Contract grant numbers: CA63464; CA54281; CA136792; Contract grant sponsor: NINDS and Office for Research in Women's Health; Contract grant number: R01NS45012; Contract grant sponsor: NEI; Contract grant numbers: R01EY015473; R01EY015872.; Funding support for the GENEVA genome-wide association studies was provided through the NIH Genes, Environment and Health Initiative (GEI). Some studies also received support from individual NIH Institutes. Barnes (U01HG004738); Beaty (NIDCR: U01DE018993, NIH contract: HHSN268200782096C); Bierut (U01HG004422, NIAAA: U10AA008401, NIDA: P01CA089392, R01DA013423, NIH contract: HHSN268200782096C); Boerwinkle (U01HG004402, NHLBI: N01HC55015, N01HC55016, N01HC55018, N01HC55019, N01HC-55020, N01HC-55021, N01HC55022, R01HL087641, R01HL59367, R01HL086694, NIH contract: HHSN268200625226C, NIH Roadmap for Medical Research: UL1RR025005); Caporaso (Z01CP010200); Fornage (U01HG004729); Hu (U01HG004399); Haiman (U01HG004726, NCI: CA63464, CA54281, CA136792); Heit (U01HG004735); Lowe (U01HG004415); Marazita (NIDCR: U01DE018903, NIH contract: HHSN268200782096C); Mitchell (U01HG004436, NINDS and Office for Research in Women's Health: R01NS45012); Murray (U01HG004423); Pasquale [U01HG004728, NEI: R01EY015473, NEI: R01EY015872 (J.L. Wiggs)]. Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the GENEVA Coordinating Center (U01HG004446). Assistance with data cleaning was provided by the National Center for Biotechnology Information. Genotyping was performed at the Broad Institute of MIT and Harvard, with funding support from the NIH GEI (U01HG04424), and Johns Hopkins University Center for Inherited Disease Research, with support from the NIH GEI (U01HG004438) and the NIH contract "High throughput genotyping for studying the genetic contributions to human disease" (HHSN268200782096C). Funding support was also provided, in part, by the Intramural Research Program of the NIH, National Library of Medicine. M. C. Cornelis is a recipient of a Canadian Institutes of Health Research Fellowship. A. Agrawal is supported by grants from the NIDA. K. C. Barnes is supported in part by the Mary Beryl Patch Turnbull Scholar Program. L. R. Pasquale is supported by a Research to Prevent Blindness Physician Scientist Award. NR 31 TC 18 Z9 19 U1 2 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD APR PY 2011 VL 35 IS 3 BP 159 EP 173 DI 10.1002/gepi.20564 PG 15 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 734KL UT WOS:000288332900005 PM 21284036 ER PT J AU Thomas, E Liang, TJ AF Thomas, Emmanuel Liang, T. Jake TI Ribavirin Enhances Interferon-Stimulated Gene Transcription by Activation of the Interferon-Stimulated Response Element Reply SO HEPATOLOGY LA English DT Letter ID EXPRESSION; PATHWAYS C1 [Thomas, Emmanuel; Liang, T. Jake] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. RP Thomas, E (reprint author), NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. NR 6 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD APR PY 2011 VL 53 IS 4 BP 1402 EP 1402 DI 10.1002/hep.24226 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 748VA UT WOS:000289419600038 ER PT J AU Clifford, RJ Buetow, KH AF Clifford, Robert J. Buetow, Kenneth H. TI Warning: Genome-wide Association Studies Can Be Misleading. An Example in Hepatology Reply SO HEPATOLOGY LA English DT Letter C1 [Clifford, Robert J.; Buetow, Kenneth H.] NCI, Lab Populat Genet, Bethesda, MD 20892 USA. RP Clifford, RJ (reprint author), NCI, Lab Populat Genet, Bethesda, MD 20892 USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD APR PY 2011 VL 53 IS 4 BP 1408 EP 1409 DI 10.1002/hep.24240 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 748VA UT WOS:000289419600046 ER PT J AU Cideciyan, AV Rachel, RA Aleman, TS Swider, M Schwartz, SB Sumaroka, A Roman, AJ Stone, EM Jacobson, SG Swaroop, A AF Cideciyan, Artur V. Rachel, Rivka A. Aleman, Tomas S. Swider, Malgorzata Schwartz, Sharon B. Sumaroka, Alexander Roman, Alejandro J. Stone, Edwin M. Jacobson, Samuel G. Swaroop, Anand TI Cone photoreceptors are the main targets for gene therapy of NPHP5 (IQCB1) or NPHP6 (CEP290) blindness: generation of an all-cone Nphp6 hypomorph mouse that mimics the human retinal ciliopathy SO HUMAN MOLECULAR GENETICS LA English DT Article ID LEBER CONGENITAL AMAUROSIS; SENIOR-LOKEN SYNDROME; RETINITIS-PIGMENTOSA; JOUBERT-SYNDROME; OUTER SEGMENT; CENTROSOMAL PROTEIN; MUTATIONS RESULT; ABYSSINIAN CATS; DEGENERATION; DISEASE AB Leber congenital amaurosis (LCA), a severe autosomal recessive childhood blindness, is caused by mutations in at least 15 genes. The most common molecular form is a ciliopathy due to NPHP6 (CEP290) mutations and subjects have profound loss of vision. A similarly severe phenotype occurs in the related ciliopathy NPHP5 (IQCB1)-LCA. Recent success of retinal gene therapy in one form of LCA prompted the question whether we know enough about human NPHP5 and NPHP6 disease to plan such treatment. We determined that there was early-onset rapid degeneration of rod photoreceptors in young subjects with these ciliopathies. Rod outer segment (OS) lamination, when detectable, was disorganized. Retinal pigment epithelium lipofuscin accumulation indicated that rods had existed in the past in most subjects. In contrast to early rod losses, the all-cone human fovea in NPHP5- and NPHP6-LCA of all ages retained cone nuclei, albeit with abnormal inner segments and OS. The rd16 mouse, carrying a hypomorphic Nphp6 allele, was a good model of the rod-dominant human extra-foveal retina. Rd16 mice showed normal genesis of photoreceptors, including the formation of cilia, followed by abnormal elaboration of OS and rapid degeneration. To produce a model of the all-cone human fovea in NPHP6-LCA, we generated rd16; Nrl(-/-) double-mutant mice. They showed substantially retained cone photoreceptors with disproportionate cone function loss, such as in the human disease. NPHP5- and NPHP6-LCA across a wide age spectrum are thus excellent candidates for cone-directed gene augmentation therapy, and the rd16; Nrl(-/-) mouse is an appropriate model for pre-clinical proof-of-concept studies. C1 [Cideciyan, Artur V.; Aleman, Tomas S.; Swider, Malgorzata; Schwartz, Sharon B.; Sumaroka, Alexander; Roman, Alejandro J.; Jacobson, Samuel G.] Univ Penn, Scheie Eye Inst, Dept Ophthalmol, Philadelphia, PA 19104 USA. [Rachel, Rivka A.; Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA. [Stone, Edwin M.] Univ Iowa, Howard Hughes Med Inst, Carver Coll Med, Iowa City, IA 52242 USA. [Stone, Edwin M.] Univ Iowa, Dept Ophthalmol, Carver Coll Med, Iowa City, IA 52242 USA. RP Cideciyan, AV (reprint author), Univ Penn, Scheie Eye Inst, Dept Ophthalmol, 51 N 39th St, Philadelphia, PA 19104 USA. EM cideciya@mail.med.upenn.edu OI Swaroop, Anand/0000-0002-1975-1141 FU Grousbeck Foundation; National Eye Institute; Macula Vision Research Foundation; Foundation Fighting Blindness; Hope for Vision FX Supported in part by Grousbeck Foundation, intramural funds from the National Eye Institute, Macula Vision Research Foundation, Foundation Fighting Blindness, and Hope for Vision. A. V. C. is a RPB Senior Scientific Investigator. NR 61 TC 38 Z9 38 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD APR 1 PY 2011 VL 20 IS 7 BP 1411 EP 1423 DI 10.1093/hmg/ddr022 PG 13 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 733RB UT WOS:000288279300015 PM 21245082 ER PT J AU Shirendeb, U Reddy, AP Manczak, M Calkins, MJ Mao, PZ Tagle, DA Reddy, PH AF Shirendeb, Ulziibat Reddy, Arubala P. Manczak, Maria Calkins, Marcus J. Mao, Peizhong Tagle, Danilo A. Reddy, P. Hemachandra TI Abnormal mitochondrial dynamics, mitochondrial loss and mutant huntingtin oligomers in Huntington's disease: implications for selective neuronal damage SO HUMAN MOLECULAR GENETICS LA English DT Article ID BASAL GANGLIA VOLUME; ALZHEIMERS-DISEASE; AMYLOID-BETA; IN-VIVO; MEMBRANE ASSOCIATION; SCAN INVESTIGATIONS; OXIDATIVE DAMAGE; TOMOGRAPHIC SCAN; MOUSE MODELS; TRAFFICKING AB The purpose of our study was to determine the relationship between mutant huntingtin (Htt) and mitochondrial dynamics in the progression of Huntington's disease (HD). We measured the mRNA levels of electron transport chain genes, and mitochondrial structural genes, Drp1 (dynamin-related protein 1), Fis1 (fission 1), Mfn1 (mitofusin 1), Mfn2 (mitofusin 2), Opa1 (optric atrophy 1), Tomm40 (translocase of outermembrane 40) and CypD (cyclophilin D) in grade III and grade IV HD patients and controls. The mutant Htt oligomers and the mitochondrial structural proteins were quantified in the striatum and frontal cortex of HD patients. Changes in expressions of the electron transport chain genes were found in HD patients and may represent a compensatory response to mitochondrial damage caused by mutant Htt. Increased expression of Drp1 and Fis1 and decreased expression of Mfn1, Mfn2, Opa1 and Tomm40 were found in HD patients relative to the controls. CypD was upregulated in HD patients, and this upregulation increased as HD progressed. Significantly increased immunoreactivity of 8-hydroxy-guanosine was found in the cortical specimens from stage III and IV HD patients relative to controls, suggesting increased oxidative DNA damage in HD patients. In contrast, significantly decreased immunoreactivities of cytochrome oxidase 1 and cytochrome b were found in HD patients relative to controls, indicating a loss of mitochondrial function in HD patients. Immunoblotting analysis revealed 15, 25 and 50 kDa mutant Htt oligomers in the brain specimens of HD patients. All oligomeric forms of mutant Htt were significantly increased in the cortical tissues of HD patients, and mutant Htt oligomers were found in the nucleus and in mitochondria. The increase in Drp1, Fis1 and CypD and the decrease in Mfn1 and Mfn2 may be responsible for abnormal mitochondrial dynamics that we found in the cortex of HD patients, and may contribute to neuronal damage in HD patients. The presence of mutant Htt oligomers in the nucleus of HD neurons and in mitochondria may disrupt neuronal functions. Based on these findings, we propose that mutant Htt in association with mitochondria imbalance and mitochondrial dynamics impairs axonal transport of mitochondria, decreases mitochondrial function and damages neurons in affected brain regions of HD patients. C1 [Shirendeb, Ulziibat; Reddy, Arubala P.; Manczak, Maria; Calkins, Marcus J.; Mao, Peizhong; Reddy, P. Hemachandra] Oregon Hlth & Sci Univ, Div Neurosci, Oregon Natl Primate Res Ctr, Neurogenet Lab, Beaverton, OR 97006 USA. [Reddy, P. Hemachandra] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA. [Tagle, Danilo A.] NINDS, NIH, Ctr Neurosci, Bethesda, MD 20892 USA. RP Reddy, PH (reprint author), Oregon Hlth & Sci Univ, Div Neurosci, Oregon Natl Primate Res Ctr, Neurogenet Lab, 505 NW 185th Ave, Beaverton, OR 97006 USA. EM reddyh@ohsu.edu FU NIH [AG028072, AG026051, RR00163, S10RR024585]; Alzheimer Association [IIRG-09-92429]; Vertex Pharmaceuticals; Medivation, Inc. FX This research was supported by NIH grants AG028072, AG026051, RR00163 and S10RR024585, Alzheimer Association grant IIRG-09-92429, Vertex Pharmaceuticals and Medivation, Inc. NR 65 TC 131 Z9 131 U1 1 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD APR 1 PY 2011 VL 20 IS 7 BP 1438 EP 1455 DI 10.1093/hmg/ddr024 PG 18 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 733RB UT WOS:000288279300017 PM 21257639 ER PT J AU Clark, TR Ellison, DW Kleba, B Hackstadt, T AF Clark, Tina R. Ellison, Damon W. Kleba, Betsy Hackstadt, Ted TI Complementation of Rickettsia rickettsii RelA/SpoT Restores a Nonlytic Plaque Phenotype SO INFECTION AND IMMUNITY LA English DT Article ID MOUNTAIN-SPOTTED-FEVER; CELL INJURY; STRINGENT RESPONSE; ENDOTHELIAL-CELLS; (P)PPGPP; BACTERIAL; STRAINS; TRANSCRIPTION; MUTAGENESIS; PROWAZEKII AB Spotted fever group rickettsiae are known to produce distinct plaque phenotypes. Strains that cause lytic infections in cell culture form clear plaques, while nonlytic strains form opaque plaques in which the cells remain intact. Clear plaques have historically been associated with more-virulent species or strains of spotted fever group rickettsiae. We have selected spontaneous mutant pairs from two independent strains of Rickettsia rickettsii, the virulent R strain and the avirulent Iowa strain. A nonlytic variant of R. rickettsii R, which typically produces clear plaques, was isolated and stably maintained. A lytic variant of the Iowa strain, which characteristically produces opaque plaques, was also selected and maintained. Genomic resequencing of the variants identified only a single gene disrupted in each strain. In both cases, the mutation was in a gene annotated as relA/spoT-like. In the Iowa strain, a single mutation introduced a premature stop codon upstream from region encoding the predicted active site of RelA/SpoT and caused the transition to a lytic plaque phenotype. In R. rickettsii R, the nonlytic plaque phenotype resulted from a single-nucleotide substitution that shifted a tyrosine residue to histidine near the active site of the enzyme. The intact relA/spoT gene thus occurred in variants with the nonlytic plaque phenotype. Complementation of the truncated relA/spoT gene in the Iowa lytic plaque variant restored the nonlytic phenotype. The relA/spoT mutations did not affect the virulence of either strain in a Guinea pig model of infection; R strain lytic and nonlytic variants both induced fever equally, and the mutation in Iowa to a lytic phenotype did not cause them to become virulent. C1 [Clark, Tina R.; Ellison, Damon W.; Kleba, Betsy; Hackstadt, Ted] NIAID, Host Parasite Interact Sect, Intracellular Parasites Lab, NIH,Rocky Mt Labs, Hamilton, MT 59840 USA. RP Hackstadt, T (reprint author), NIAID, Host Parasite Interact Sect, Intracellular Parasites Lab, NIH,Rocky Mt Labs, 903 S 4th St, Hamilton, MT 59840 USA. EM ted_hackstadt@nih.gov FU Division of Intramural Research of the National Institute for Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by the Division of Intramural Research of the National Institute for Allergy and Infectious Diseases, National Institutes of Health. NR 35 TC 17 Z9 17 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD APR PY 2011 VL 79 IS 4 BP 1631 EP 1637 DI 10.1128/IAI.00048-11 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 736YX UT WOS:000288532300025 PM 21300770 ER PT J AU Morrell, CN Srivastava, K Swaim, A Lee, MT Chen, J Nagineni, C Hooks, JJ Detrick, B AF Morrell, Craig N. Srivastava, Kalyan Swaim, AnneMarie Lee, M. Teresa Chen, Jun Nagineni, Chandrashakaharam Hooks, John J. Detrick, Barbara TI Beta Interferon Suppresses the Development of Experimental Cerebral Malaria SO INFECTION AND IMMUNITY LA English DT Article ID INDUCED MICROVASCULAR PATHOLOGY; PIGMENT EPITHELIAL-CELLS; BRAIN; INFLAMMATION; EXPRESSION; CHEMOKINES; PLATELETS; MIGRATION; GENESIS; RETINA AB Cerebral malaria (CM) is a major complication of Plasmodium falciparum infection, particularly in children. The pathogenesis of cerebral malaria involves parasitized red blood cell (RBC)-mediated vascular inflammation, immune stimulation, loss of blood-brain barrier integrity, and obstruction of cerebral capillaries. Therefore, blunting vascular inflammation and immune cell recruitment is crucial in limiting the disease course. Beta interferon (IFN-beta) has been used in the treatment of diseases, such as multiple sclerosis (MS) but has not yet been explored in the treatment of CM. Therefore, we sought to determine whether IFN-beta also limits disease progression in experimental cerebral malaria (ECM). Plasmodium berghei-infected mice treated with IFN-beta died later and showed increased survival, with improved blood-brain barrier function, compared to infected mice. IFN-beta did not alter systemic parasitemia. However, we identified multiple action sites that were modified by IFN-beta administration. P. berghei infection resulted in increased expression of chemokine (C-X-C motif) ligand 9 (CXCL9) in brain vascular endothelial cells that attract T cells to the brain, as well as increased T-cell chemokine (C-X-C motif) receptor 3 (CXCR3) expression. The infection also increased the cellular content of intercellular adhesion molecule 1 (ICAM-1), a molecule important for attachment of parasitized RBCs to the endothelial cell. In this article, we report that IFN-beta treatment leads to reduction of CXCL9 and ICAM-1 in the brain, reduction of T-cell CXCR3 expression, and downregulation of serum tumor necrosis factor alpha (TNF-alpha). In addition, IFN-beta-treated P. berghei-infected mice also had fewer brain T-cell infiltrates, further demonstrating its protective effects. Hence, IFN-beta has important anti-inflammatory properties that ameliorate the severity of ECM and prolong mouse survival. C1 [Lee, M. Teresa; Detrick, Barbara] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21287 USA. [Morrell, Craig N.; Srivastava, Kalyan] Univ Rochester, Aab Cardiovasc Res Inst, Sch Med & Dent, Rochester, NY 14642 USA. [Swaim, AnneMarie] Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Pathobiol, Baltimore, MD 21287 USA. [Chen, Jun; Nagineni, Chandrashakaharam; Hooks, John J.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Detrick, B (reprint author), Johns Hopkins Univ, Sch Med, Dept Pathol, Meyer B125A,600 N Wolfe St, Baltimore, MD 21287 USA. EM bdetrick@jhmi.edu FU National Institutes of Health [NIH/NHLBI 1R01HL093179]; Johns Hopkins University School of Public Health Malaria Research Institute; NEI, NIH FX This work was supported by a National Institutes of Health grant (NIH/NHLBI 1R01HL093179) and grants from The Johns Hopkins University School of Public Health Malaria Research Institute (to C.N.M.) and by the Intramural Research Program, NEI, NIH, to J.J.H. NR 27 TC 26 Z9 27 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD APR PY 2011 VL 79 IS 4 BP 1750 EP 1758 DI 10.1128/IAI.00810-10 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 736YX UT WOS:000288532300038 PM 21245265 ER PT J AU Castle, PE Gage, JC AF Castle, Philip E. Gage, Julia C. TI Re: Preventing Cervical Cancer Globally by Acting Locally: If Not Now, When? Response SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 [Castle, Philip E.] Amer Soc Clin Pathologists, Amer Soc Clin Pathol Inst, Washington, DC 20005 USA. [Gage, Julia C.] NCI, Clin Genet Branch, Div Canc Epidemiol and Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Castle, PE (reprint author), Amer Soc Clin Pathologists, Amer Soc Clin Pathol Inst, 1225 New York Ave NW,Ste 250, Washington, DC 20005 USA. EM philip.castle@ascp.org NR 7 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD APR PY 2011 VL 103 IS 7 BP 612 EP 613 DI 10.1093/jnci/djr050 PG 2 WC Oncology SC Oncology GA 747GH UT WOS:000289307800019 ER PT J AU Voth, DE Beare, PA Howe, D Sharma, UM Samoilis, G Cockrell, DC Omsland, A Heinzen, RA AF Voth, Daniel E. Beare, Paul A. Howe, Dale Sharma, Uma M. Samoilis, Georgios Cockrell, Diane C. Omsland, Anders Heinzen, Robert A. TI The Coxiella burnetii Cryptic Plasmid Is Enriched in Genes Encoding Type IV Secretion System Substrates SO JOURNAL OF BACTERIOLOGY LA English DT Article ID LEGIONELLA-PNEUMOPHILA; HOST-CELL; Q-FEVER; HUMAN MACROPHAGES; PARASITOPHOROUS VACUOLE; EFFECTOR PROTEINS; PHASE-I; IDENTIFICATION; TRANSLOCATION; EXPLOITATION AB The intracellular bacterial pathogen Coxiella burnetii directs biogenesis of a phagolysosome-like parasitophorous vacuole (PV), in which it replicates. The organism encodes a Dot/Icm type IV secretion system (T4SS) predicted to deliver to the host cytosol effector proteins that mediate PV formation and other cellular events. All C. burnetii isolates carry a large, autonomously replicating plasmid or have chromosomally integrated plasmid-like sequences (IPS), suggesting that plasmid and IPS genes are critical for infection. Bioinformatic analyses revealed two candidate Dot/Icm substrates with eukaryotic-like motifs uniquely encoded by the QpH1 plasmid from the Nine Mile reference isolate. CpeC, containing an F-box domain, and CpeD, possessing kinesin-related and coiled-coil regions, were secreted by the closely related Legionella pneumophila Dot/Icm T4SS. An additional QpH1-specific gene, cpeE, situated in a predicted operon with cpeD, also encoded a secreted effector. Further screening revealed that three hypothetical proteins (CpeA, CpeB, and CpeF) encoded by all C. burnetii plasmids and IPS are Dot/Icm substrates. By use of new genetic tools, secretion of plasmid effectors by C. burnetii during host cell infection was confirmed using beta-lactamase and adenylate cyclase translocation assays, and a C-terminal secretion signal was identified. When ectopically expressed in HeLa cells, plasmid effectors trafficked to different subcellular sites, including autophagosomes (CpeB), ubiquitin-rich compartments (CpeC), and the endoplasmic reticulum (CpeD). Collectively, these results suggest that C. burnetii plasmid-encoded T4SS substrates play important roles in subversion of host cell functions, providing a plausible explanation for the absolute maintenance of plasmid genes by this pathogen. C1 [Voth, Daniel E.; Sharma, Uma M.] Univ Arkansas Med Sci, Dept Microbiol & Immunol, Little Rock, AR 72205 USA. [Beare, Paul A.; Howe, Dale; Cockrell, Diane C.; Omsland, Anders; Heinzen, Robert A.] NIAID, Coxiella Pathogenesis Sect, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. [Samoilis, Georgios] Univ Crete, Dept Chem, Iraklion, Greece. [Samoilis, Georgios] Univ Crete, Dept Clin Bacteriol, Iraklion, Greece. RP Voth, DE (reprint author), Univ Arkansas Med Sci, Dept Microbiol & Immunol, 4301 W Markham St, Little Rock, AR 72205 USA. EM dvoth@uams.edu FU NIH NIAID [K22AI081753, R01AI087669]; Arkansas Biosciences Institute; National Institutes of Health, National Institute of Allergy and Infectious Diseases FX This work was supported by funding from NIH NIAID grants K22AI081753 (D.E.V.) and R01AI087669 (D.E.V.), the Arkansas Biosciences Institute (D.E.V.), and the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases (R.A.H.). NR 68 TC 62 Z9 62 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD APR PY 2011 VL 193 IS 7 BP 1493 EP 1503 DI 10.1128/JB.01359-10 PG 11 WC Microbiology SC Microbiology GA 734DW UT WOS:000288314400001 PM 21216993 ER PT J AU Kadoya, R Baek, JH Sarker, A Chattoraj, DK AF Kadoya, Ryosuke Baek, Jong Hwan Sarker, Arnab Chattoraj, Dhruba K. TI Participation of Chromosome Segregation Protein ParAI of Vibrio cholerae in Chromosome Replication SO JOURNAL OF BACTERIOLOGY LA English DT Article ID BACTERIAL-DNA SEGREGATION; TUBULIN HOMOLOG TUBZ; BACILLUS-SUBTILIS; ESCHERICHIA-COLI; F-PLASMID; PSEUDOMONAS-AERUGINOSA; PARTITIONING PROTEINS; CAULOBACTER-CRESCENTUS; ACTIN HOMOLOG; SPO0J PARB AB Vibrio cholerae carries homologs of plasmid-borne parA and parB genes on both of its chromosomes. The par genes help to segregate many plasmids and chromosomes. Here we have studied the par genes of V. cholerae chromosome I. Earlier studies suggested that ParBI binds to the centromeric site parSI near the origin of replication (oriI), and parSI-ParBI complexes are placed at the cell poles by ParAI. Deletion of parAI and parSI caused the origin-proximal DNA to be less polar. Here we found that deletion of parBI also resulted in a less polar localization of oriI. However, unlike the deletion of parAI, the deletion of parBI increased the oriI number. Replication was normal when both parAI and parBI were deleted, suggesting that ParBI mediates its action through ParAI. Overexpression of ParAI in a parABI-deleted strain also increased the DNA content. The results are similar to those found for Bacillus subtilis, where ParA (Soj) stimulates replication and this activity is repressed by ParB (SpoOJ). As in B. subtilis, the stimulation of replication most likely involves the replication initiator DnaA. Our results indicate that control of chromosomal DNA replication is an additional function of chromosomal par genes conserved across the Gram-positive/Gram-negative divide. C1 [Kadoya, Ryosuke; Baek, Jong Hwan; Sarker, Arnab; Chattoraj, Dhruba K.] NCI, Biochem & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Chattoraj, DK (reprint author), NCI, Biochem & Mol Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Rm 6044, Bethesda, MD 20892 USA. EM chattoraj@nih.gov FU Center for Cancer Research, National Cancer Institute FX This work was supported by the Intramural Research Program, Center for Cancer Research, National Cancer Institute. NR 76 TC 28 Z9 28 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD APR PY 2011 VL 193 IS 7 BP 1504 EP 1514 DI 10.1128/JB.01067-10 PG 11 WC Microbiology SC Microbiology GA 734DW UT WOS:000288314400002 PM 21257772 ER PT J AU Shevach, EM AF Shevach, Ethan M. TI The Resurrection of T Cell-Mediated Suppression SO JOURNAL OF IMMUNOLOGY LA English DT Editorial Material ID AUTOIMMUNE-DISEASES; SELF-TOLERANCE; MICE; SUBSET; THYROIDITIS; THYMECTOMY; PREVENTION; COMPLEX; INDUCE; RATS C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Shevach, EM (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room 11N315,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA. EM eshevach@niaid.nih.gov NR 26 TC 11 Z9 12 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2011 VL 186 IS 7 BP 3805 EP 3807 DI 10.4049/jimmunol.1100364 PG 3 WC Immunology SC Immunology GA 739WH UT WOS:000288751200002 PM 21422250 ER PT J AU Anderson, R Crane, D Bosio, C AF Anderson, Rebecca Crane, Deborah Bosio, Catharine TI Presence of long lived bone marrow effector cells mediate protection against a virulent bacterial pathogen SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Anderson, Rebecca; Crane, Deborah; Bosio, Catharine] NIAID, Rocky Mt Labs, Hamilton, MT 59840 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 99.30 PG 2 WC Immunology SC Immunology GA V44LY UT WOS:000209751703002 ER PT J AU Baker, C Comrie, W Fedorchuk, C Hyun, YM Meier-Schellersheim, M Kim, M AF Baker, Christina Comrie, William Fedorchuk, Christine Hyun, Young-Min Meier-Schellersheim, Martin Kim, Minsoo TI RhoH is a key functional determinant of the "stop and go" nature of CD4+T cells during activation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Baker, Christina; Fedorchuk, Christine; Hyun, Young-Min; Kim, Minsoo] Univ Rochester, Rochester, NY USA. [Meier-Schellersheim, Martin] NIAID, NIH, Bethesda, MD 20892 USA. [Comrie, William] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 109.17 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751704103 ER PT J AU Bao, L Dunham, K Lucas, K AF Bao, Lei Dunham, Kimberly Lucas, Kenneth TI Decitabine and Interferon-gamma enhance neuroblastoma cells susceptibility to CTL-mediated killing SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Bao, Lei; Lucas, Kenneth] Penn State Univ, Childrens Hosp, Hershey, PA USA. [Dunham, Kimberly] NCI, SAIC Frederick, NIH, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 156.26 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751707002 ER PT J AU Barron, L Smith, A El Kasmi, K Qualls, J Huang, XZ Wynn, T Murray, P AF Barron, Luke Smith, Amber El Kasmi, Karim Qualls, Joseph Huang, Xiaozhu Wynn, Thomas Murray, Peter TI Genetic analysis of arginase 1 in Th2-dominated lung inflammation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Barron, Luke; Wynn, Thomas] NIAID, Parasit Dis Lab, Bethesda, MD USA. [Smith, Amber; El Kasmi, Karim; Qualls, Joseph; Murray, Peter] St Jude Childrens Res Hosp, Dept Infect Dis, Memphis, TN 38105 USA. [Smith, Amber; El Kasmi, Karim; Qualls, Joseph; Murray, Peter] St Jude Childrens Res Hosp, Dept Immunol, Memphis, TN 38105 USA. [Huang, Xiaozhu] Univ Calif San Francisco, Sandler Asthma Basic Res Ctr, San Francisco, CA 94143 USA. [El Kasmi, Karim] Univ Colorado, Dept Pediat, Denver, CO 80202 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 163.12 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751707130 ER PT J AU Berezhnoy, A Stewart, C Giagrande, P McNamara, J Trinchieri, G Gilboa, E AF Berezhnoy, Alexey Stewart, Charles Giagrande, Paloma McNamara, James Trinchieri, Giorgio Gilboa, Eli TI RNA aptamer against the IL-10 receptor block IL-10 function in vitro and in vivo SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Berezhnoy, Alexey; Gilboa, Eli] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA. [Stewart, Charles; Trinchieri, Giorgio] NCI, Canc Inflammat Program, CCR, Frederick, MD 21701 USA. [Giagrande, Paloma; McNamara, James] Univ Iowa, Mol & Cellular Biol Program, Iowa City, IA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 66.46 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751702147 ER PT J AU Bodogai, M Olkhanud, P Rochman, Y Malchinkhuu, E Wejksza, K Gress, R Hesdorffer, C Leonard, W Biragyn, A AF Bodogai, Monica Olkhanud, Purevdorj Rochman, Yrina Malchinkhuu, Enkhzol Wejksza, Katarzyna Gress, Ronald Hesdorffer, Charles Leonard, Warren Biragyn, Arya TI Thymic stromal lymphopoietin mediates breast cancer progression and metastasis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Bodogai, Monica; Olkhanud, Purevdorj; Malchinkhuu, Enkhzol; Wejksza, Katarzyna; Hesdorffer, Charles; Biragyn, Arya] NIA, NIH, Baltimore, MD 21224 USA. [Rochman, Yrina; Leonard, Warren] NHLBI, NIH, Bethesda, MD 20892 USA. [Gress, Ronald] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 48.9 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751700147 ER PT J AU Bosio, C Crane, D AF Bosio, Catharine Crane, Deborah TI Cellular and soluble requirements for survival of pulmonary infection with virulent Francisella tularensis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Bosio, Catharine; Crane, Deborah] NIAID, LICP, NIH, Hamilton, MT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 99.29 PG 2 WC Immunology SC Immunology GA V44LY UT WOS:000209751703023 ER PT J AU Caspi, R Horai, R Chen, J Hansen, A McManigle, W Villasmil, R Silver, P AF Caspi, Rachel Horai, Reiko Chen, Jun Hansen, Anna McManigle, William Villasmil, Rafael Silver, Phyllis TI Retina-specific T regulatory cells accumulate in the eye during autoimmune uveitis and act to control inflammation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Caspi, Rachel; Horai, Reiko; Chen, Jun; Hansen, Anna; McManigle, William; Villasmil, Rafael; Silver, Phyllis] NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 115.22 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751705069 ER PT J AU Chan, C Bai, Y Maric, I Klion, A Metcalfe, D Wilson, T AF Chan, Ching Bai, Yun Maric, Irina Klion, Amy Metcalfe, Dean Wilson, Todd TI Expression of KIT isoforms in systemic mastocytosis: correlation with disease severity and KITD816V SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Chan, Ching; Bai, Yun; Metcalfe, Dean; Wilson, Todd] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. [Maric, Irina] NIH, Clin Pathol Dept, Bethesda, MD 20892 USA. [Klion, Amy] NIH, Eosinophil Pathol Unit, Parasit Dis Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 153.32 PG 2 WC Immunology SC Immunology GA V44LY UT WOS:000209751706093 ER PT J AU Chen, KQ Liu, Y Xiang, Y Huang, JQ Le, YY Gong, WH Yoshimura, T Tessarollo, L Gao, JL Wang, JM AF Chen, Keqiang Liu, Ying Xiang, Yi Huang, Jiaqiang Le, Yingying Gong, Wanghua Yoshimura, Teizo Tessarollo, Lino Gao, Ji-liang Wang, Ji Ming TI Involvement of mFPR2 in dendritic cell maturation and trafficking SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Chen, Keqiang; Liu, Ying; Yoshimura, Teizo; Wang, Ji Ming] NCI, CCR, CIP, LMI,NIH, Frederick, MD 21701 USA. [Xiang, Yi] Ruijin Hosp, Sch Med, Shanghai, Peoples R China. [Huang, Jiaqiang] QIAGEN SA Biosci Corp, Frederick, MD USA. [Le, Yingying] Inst Nutr Sci, Shanghai, Peoples R China. [Gong, Wanghua] SAIC Frederick, Frederick, MD USA. [Tessarollo, Lino] Mouse Canc Genet Program, Frederick, MD USA. [Gao, Ji-liang] Lab Mol Immunol, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 147.20 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751705179 ER PT J AU Chen, Q AF Chen, Qian TI IL-2 controls the stability of Foxp3 expression in TGF-beta-induced Foxp3+T cells in vivo SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Chen, Qian] NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 115.11 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751705068 ER PT J AU Crampton, S Deane, J Otubusin, O Hasty, K Bolland, S AF Crampton, Steve Deane, Jonathan Otubusin, Owokunile Hasty, Karen Bolland, Silvia TI Transgenic expression of MDA5 enhances interferon responses, CD8 activation, and viral clearance SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Crampton, Steve; Otubusin, Owokunile; Hasty, Karen; Bolland, Silvia] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Deane, Jonathan] Novartis Res Fdn, Genom Inst, San Diego, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 110.19 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751704127 ER PT J AU Creusot, R Junttila, I Bates, D Moraga, I Lupardus, P Fathman, CG Paul, W Garcia, KC AF Creusot, Remi Junttila, Ilkka Bates, Darren Moraga, Ignacio Lupardus, Patrick Fathman, C. Garrison Paul, William Garcia, K. Christopher TI Engineering cell-type selective immune responses using mechanism-based designer IL-4 cytokines. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Creusot, Remi; Bates, Darren; Moraga, Ignacio; Lupardus, Patrick; Fathman, C. Garrison; Garcia, K. Christopher] Stanford Univ, Sch Med, Stanford, CA 94305 USA. NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 57.8 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751701139 ER PT J AU Cruz, A Ramaswamy, M Siegel, R AF Cruz, Anthony Ramaswamy, Madhu Siegel, Richard TI Sensitivity of CD4+effector memory T cells to Fas-induced apoptosis is due to increased localization of Fas to lipid raft microdomains SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Cruz, Anthony; Ramaswamy, Madhu; Siegel, Richard] NIAMS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 104.9 PG 2 WC Immunology SC Immunology GA V44LY UT WOS:000209751703171 ER PT J AU Cui, YZ Garber, H Mackall, C AF Cui, Yongzhi Garber, Haven Mackall, Crystal TI Survivin TCR transgenic mice develop T cell lymphoblastic lymphoma SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Cui, Yongzhi; Garber, Haven; Mackall, Crystal] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 48.25 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751700135 ER PT J AU Dickinson, G Liu, HQ Shriner, A Leonard, W Alugupalli, K AF Dickinson, Gregory Liu, Hongqi Shriner, Anne Leonard, Warren Alugupalli, Kishore TI Thymic stromal lymphopoietin can restore functional T cell-independent antibody responses in young mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Dickinson, Gregory; Liu, Hongqi; Shriner, Anne; Alugupalli, Kishore] Thomas Jefferson Univ, Microbiol & Immunol, Philadelphia, PA 19107 USA. [Leonard, Warren] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 150.5 PG 2 WC Immunology SC Immunology GA V44LY UT WOS:000209751706024 ER PT J AU Doyle, A Jacobsen, E Ochkur, S McGarry, M Shim, K Nguyen, D Protheroe, C Colbert, D Dyer, K Rosenberg, H Lee, N Lee, J AF Doyle, Alfred Jacobsen, Elizabeth Ochkur, Sergei McGarry, Michael Shim, Kevin Nguyen, David Protheroe, Cheryl Colbert, Dana Dyer, Kimberly Rosenberg, Helene Lee, Nancy Lee, James TI The expression of the abundant secondary granule proteins MBP-1 and EPO is required for the maturation of eosinophil-lineage committed progenitor cells in the hematopoietic compartments of mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Doyle, Alfred; Jacobsen, Elizabeth; Ochkur, Sergei; McGarry, Michael; Shim, Kevin; Nguyen, David; Protheroe, Cheryl; Lee, James] Mayo Clin Arizona, Div Pulm Med, Scottsdale, AZ USA. [Colbert, Dana; Lee, Nancy] Mayo Clin Arizona, Div Hematol & Oncol, Scottsdale, AZ USA. [Dyer, Kimberly; Rosenberg, Helene] NIAID, NIH, Eosinophil Biol Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 153.27 PG 2 WC Immunology SC Immunology GA V44LY UT WOS:000209751706124 ER PT J AU Dzutsev, A Koo, L Sui, Y Gagnon, S Schwartz, O Belyakov, I Berzofsky, J AF Dzutsev, Amiran Koo, Lily Sui, Yongjun Gagnon, Susan Schwartz, Owen Belyakov, Igor Berzofsky, Jay TI Dendritic cells patrol epithelium and the lumen of the crypts associated with the organized lymphoid tissue of the colon. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Dzutsev, Amiran] NCI, SAIC, NIH, Frederick, MD 21701 USA. [Dzutsev, Amiran; Sui, Yongjun; Gagnon, Susan; Belyakov, Igor; Berzofsky, Jay] NCI, NIH, Bethesda, MD 20892 USA. [Koo, Lily; Schwartz, Owen] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 161.1 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751707097 ER PT J AU Falanga, Y Finkelman, F Odom, S Rivera, J Oskeritzian, C Ryan, J AF Falanga, Yves Finkelman, Fred Odom, Sandra Rivera, Juan Oskeritzian, Carole Ryan, John TI Opposing roles for fyn and lyn kinases in Fc gamma R signaling and IgG-mediated systemic anaphylaxis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Falanga, Yves; Oskeritzian, Carole; Ryan, John] Virginia Commonwealth Univ, Biol, Richmond, VA USA. [Finkelman, Fred] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Odom, Sandra; Rivera, Juan] NIAMS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 163.17 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751707134 ER PT J AU Gaffen, S Conti, H Freeman, A Baker, O Li, R Jang, W Holland, S Edgerton, M AF Gaffen, Sarah Conti, Heather Freeman, Alexandra Baker, Olga Li, Rui Jang, Woong Holland, Steven Edgerton, Mira TI New mechanism of mucosal immunity in oral candidiasis: insights from Hyper-IgE (STAT3-deficient) patients SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Gaffen, Sarah] Univ Pittsburgh, Med Rheumatol, Pittsburgh, PA USA. [Gaffen, Sarah; Conti, Heather; Baker, Olga; Li, Rui; Jang, Woong; Edgerton, Mira] Univ Buffalo, Buffalo, NY USA. [Freeman, Alexandra; Holland, Steven] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 56.1 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751701134 ER PT J AU Gerner, M Ifrim, I Kastenmuller, W Germain, R AF Gerner, Michael Ifrim, Ina Kastenmuller, Wolfgang Germain, Ronald TI Distinct spatial localization of resident dendritic cell subsets in lymph nodes SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Gerner, Michael; Ifrim, Ina; Kastenmuller, Wolfgang; Germain, Ronald] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 100.30 PG 2 WC Immunology SC Immunology GA V44LY UT WOS:000209751703041 ER PT J AU Goenka, R Mathews, A O'Neill, P Scholz, J Leonard, W Stohl, W Cancro, M AF Goenka, Radhika Mathews, Andrew O'Neill, Patrick Scholz, Jean Leonard, Warren Stohl, William Cancro, Michael TI Positive selection during affinity maturation relies on T cell derived BLyS SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Goenka, Radhika; Mathews, Andrew; O'Neill, Patrick; Scholz, Jean; Cancro, Michael] Univ Penn, Philadelphia, PA 19104 USA. [Leonard, Warren] NHLBI, Bethesda, MD 20892 USA. [Stohl, William] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 61.3 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751701200 ER PT J AU Guo, XT Yang, ZY Panet, A Liu, WL Pierce, S Nabel, G AF Guo, Xiaoti Yang, Zhiyong Panet, Amos Liu, Wanli Pierce, Susan Nabel, Gary TI Expression of a functional B cell receptor with the specificity of VRC01, a broadly neutralizing antibody against HIV SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Guo, Xiaoti; Yang, Zhiyong; Nabel, Gary] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Panet, Amos] Hebrew Univ Jerusalem, Hadassah Med Sch, Jerusalem, Israel. [Liu, Wanli; Pierce, Susan] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 159.8 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751707063 ER PT J AU Hasley, R Hong, C Le Saout, C Kim, G Friesen, T Nakamura, Y Park, JH Sneller, M Roby, G Rehm, C Lane, C Catalfamo, M AF Hasley, Rebecca Hong, Changwan Le Saout, Cecile Kim, Grace Friesen, Travis Nakamura, Yoriko Park, Jung-Hyun Sneller, Michael Roby, Gregg Rehm, Catherine Lane, Clifford Catalfamo, Marta TI CD8-EOMEShigh T cells define a subpopulation of CD8 memory cells that restore CD127(high) expression after cART treatment in HIV infected patients. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Hasley, Rebecca; Le Saout, Cecile; Friesen, Travis; Nakamura, Yoriko; Sneller, Michael; Roby, Gregg; Rehm, Catherine; Lane, Clifford; Catalfamo, Marta] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Hong, Changwan; Kim, Grace; Park, Jung-Hyun] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 105.27 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751704028 ER PT J AU Hernandez, S Weinstein, J Steiner, L Bertino, S Poholek, A Gallagher, P Craft, J AF Hernandez, Sairy Weinstein, Jason Steiner, Laurie Bertino, Sarah Poholek, Amanda Gallagher, Patrick Craft, Joseph TI Migrating out of the zone: the role of P-selectin glycoprotein ligand-1 on T follicular helper cell movement SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Hernandez, Sairy; Weinstein, Jason; Steiner, Laurie; Bertino, Sarah; Gallagher, Patrick; Craft, Joseph] Yale Univ, Immunobiol, New Haven, CT USA. [Poholek, Amanda] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 60.8 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751701195 ER PT J AU Herz, J McGavern, D AF Herz, Jasmin McGavern, Dorian TI Dynamics of memory T cells clearing a persistent CNS infection in the absence of severe tissue injury SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Herz, Jasmin; McGavern, Dorian] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 53.9 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751701066 ER PT J AU Hurley, A Smith, M Karpova, T Nikel, E Packard, B Imamichi, H MacNally, J Higgins, J Sneller, M Lane, C Catalfamo, M AF Hurley, Amanda Smith, Mindy Karpova, Tatiana Nikel, Erin Packard, Beverly Imamichi, Hlromi MacNally, James Higgins, Jeanette Sneller, Michael Lane, Clifford Catalfamo, Marta TI Thrombin mediates kinesis in human resting CD8 T cells from healthy controls and HIV infected individuals through specific interaction with thrombin receptor (PAR-1). SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Hurley, Amanda; Smith, Mindy; Nikel, Erin; Imamichi, Hlromi; Sneller, Michael; Lane, Clifford; Catalfamo, Marta] NIAID, CMRS, Lab Immunoregulat, NIH, Bethesda, MD 20892 USA. [Karpova, Tatiana; MacNally, James] NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. [Higgins, Jeanette] Sci Applicat Int Corp, AIDS Monitoring Labs, Frederick, MD USA. [Packard, Beverly] Oncolmmunin Inc, Gaithersburg, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 112.7 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751704196 ER PT J AU Imamichi, T Zhang, X Zhou, M Lempicki, R Baseler, M Veenstra, T Young, H Lane, HC AF Imamichi, Tomozumi Zhang, Xing Zhou, Ming Lempicki, Richard Baseler, Michael Veenstra, Timothy Young, Howard Lane, H. Clifford TI Ku70 is a novel cytosolic DNA sensor that induces a Type-III rather than Type-I IFN via activation of IRF-1 and IRF-7. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Imamichi, Tomozumi; Zhang, Xing; Zhou, Ming; Lempicki, Richard; Baseler, Michael; Veenstra, Timothy] SAIC Frederick Inc, Frederick, MD USA. [Imamichi, Tomozumi; Zhang, Xing; Zhou, Ming; Lempicki, Richard; Baseler, Michael; Veenstra, Timothy; Young, Howard] NCI, Frederick, MD 21701 USA. [Lane, H. Clifford] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 116.11 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751705089 ER PT J AU Jung, MY Kuehn, HS Beaven, M Metcalfe, D Gilfillan, A AF Jung, Mi-Yeon Kuehn, Hye Sun Beaven, Michael Metcalfe, Dean Gilfillan, Alasdair TI Prostaglandin E2 induces activation of mTORC1 and mTORC2 in mast cells: selective utilization of mTORC2 for the regulation of chemotaxis and mediator release SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Jung, Mi-Yeon; Kuehn, Hye Sun; Metcalfe, Dean; Gilfillan, Alasdair] NIAID, NIH, Bethesda, MD 20892 USA. [Beaven, Michael] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 151.6 PG 2 WC Immunology SC Immunology GA V44LY UT WOS:000209751706054 ER PT J AU Kang, S Herz, J Kim, J Nayak, D Stewart-Hutchinson, P Dustin, M McGavern, D AF Kang, Silvia Herz, Jasmin Kim, Jiyun Nayak, Debasis Stewart-Hutchinson, Phillip Dustin, Michael McGavern, Dorian TI Migration of cytotoxic lymphocytes in cell cycle permits local MHC-I dependent control of division at sites of viral infection SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Kang, Silvia; Herz, Jasmin; McGavern, Dorian] NINDS, NIH, Bethesda, MD 20892 USA. [Kim, Jiyun; Nayak, Debasis; Stewart-Hutchinson, Phillip; Dustin, Michael] NYU, Skirball Inst, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 105.21 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751704023 ER PT J AU Kim, G Lucas, P Gress, R Park, J AF Kim, Grace Lucas, Philip Gress, Ronald Park, J. TI Thymocyte specific interleukin-7 restores T cell development but not homeostasis in IL-7KO mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Kim, Grace; Park, J.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. [Kim, Grace] NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA. [Lucas, Philip; Gress, Ronald] NCI, Exp Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 160.6 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751707073 ER PT J AU Kim, J Stewart-Hutchinson, P Kang, S McGavern, D Dustin, M AF Kim, Jiyun Stewart-Hutchinson, Phillip Kang, Silvia McGavern, Dorian Dustin, Michael TI CD8 effector cell immunological synapse and cell division in the virally infected CNS SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Kim, Jiyun; Stewart-Hutchinson, Phillip; Dustin, Michael] NYU, Sch Med, Mol Pathogenesis, New York, NY USA. [Kang, Silvia; McGavern, Dorian] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 112.20 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751704194 ER PT J AU Ko, SY Kuo, T Blumberg, R Nabel, G AF Ko, Sung-Youl Kuo, Timothy Blumberg, Richard Nabel, Gary TI Modification of VRC01 for enhancing half-life and ADCC activity SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Ko, Sung-Youl; Nabel, Gary] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Kuo, Timothy; Blumberg, Richard] Harvard Univ, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 155.39 PG 2 WC Immunology SC Immunology GA V44LY UT WOS:000209751706186 ER PT J AU Kole, H Deane, J Scott, B Bolland, S AF Kole, Hemanta Deane, Jonathan Scott, Bethany Bolland, Silvia TI VSV infection ameliorates autoimmune disease in Fc gamma R2B deficient mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Kole, Hemanta; Deane, Jonathan; Scott, Bethany; Bolland, Silvia] NIAID, AFGS, LIG, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 101.14 PG 2 WC Immunology SC Immunology GA V44LY UT WOS:000209751703083 ER PT J AU Lee, J AF Lee, Junho TI Ghrelin stimulates cell proliferation in T cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Lee, Junho] NIA, LMBI, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 APR PY 2011 VL 186 SU 1 MA 109.22 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751704111 ER PT J AU Liang, GQ Xie, ZH Charles, N Rivera, J Druey, K AF Liang, Genqing Xie, Zhihui Charles, Nicolas Rivera, Juan Druey, Kirk TI Naive T cells sense the cysteine protease allergen papain and propel basophil-mediated T helper type 2 immunity SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Liang, Genqing; Xie, Zhihui; Druey, Kirk] NIAID, Bethesda, MD 20892 USA. [Charles, Nicolas; Rivera, Juan] NIAMS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 149.13 PG 2 WC Immunology SC Immunology GA V44LY UT WOS:000209751706006 ER PT J AU Lin, FC Saleh, B Hodge, D Young, H AF Lin, Fanching Saleh, Bahara Hodge, Deborah Young, Howard TI Chronic IFN-gamma expression alters the migration pattern of peripheral T cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Lin, Fanching; Saleh, Bahara; Hodge, Deborah; Young, Howard] NCI, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 160.7 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751707083 ER PT J AU Liu, Q Malech, H Murphy, P McDermoft, D AF Liu, Qian Malech, Harry Murphy, Philip McDermoft, David TI CXCR4 blockade reverses panleukopenia in patients with WHIM syndrome SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Liu, Qian; Murphy, Philip; McDermoft, David] NIAID, Mol Microbiol Lab, Bethesda, MD 20892 USA. [Malech, Harry] NIAID, Host Def Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 153.11 PG 2 WC Immunology SC Immunology GA V44LY UT WOS:000209751706115 ER PT J AU Liu, WL Pierce, S AF Liu, Wanli Pierce, Susan TI Disk large protein 1 promotes the initiation of isotype-switched IgG-BCR signaling SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Liu, Wanli; Pierce, Susan] NIAID, LIG, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 50.15 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751700193 ER PT J AU Lu, JH Marjon, K Marnell, L Mold, C Du Clos, T Sun, P AF Lu, Jinghua Marjon, Kristopher Marnell, Lorraine Mold, Carolyn Du Clos, Terry Sun, Peter TI The Structure and Function of Acute Phase Proteins: C-Reactive Protein and Serum Amyloid A in Innate Immunity SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Lu, Jinghua; Sun, Peter] NIAID, LIG SIS, NIH, Rockville, MD USA. [Marjon, Kristopher; Marnell, Lorraine; Mold, Carolyn; Du Clos, Terry] Univ New Mexico, Dept Internal Med, Albuquerque, NM USA. [Marjon, Kristopher; Marnell, Lorraine; Mold, Carolyn; Du Clos, Terry] Univ New Mexico, Dept Mol Genet & Microbiol, Albuquerque, NM USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 APR PY 2011 VL 186 SU 1 MA 110.21 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751704130 ER PT J AU Lu, LH Niemela, J Fleisher, T Davis, J Caminha, I Natter, M Beer, L Dowdell, K Pittaluga, S Raffeld, M Rao, K Oliveira, JB AF Lu, Lianghao Niemela, Julie Fleisher, Thomas Davis, Joie Caminha, Iusta Natter, Mark Beer, Laurel Dowdell, Kennichi Pittaluga, Stefania Raffeld, Mark Rao, Koneti Oliveira, Joao Bosco TI Somatic KRAS mutations associated with a human non-malignant syndrome of autoimmunity and abnormal leukocyte homeostasis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Lu, Lianghao; Niemela, Julie; Fleisher, Thomas; Davis, Joie; Caminha, Iusta; Natter, Mark; Beer, Laurel; Dowdell, Kennichi; Pittaluga, Stefania; Raffeld, Mark; Rao, Koneti; Oliveira, Joao Bosco] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 47.4 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751700109 ER PT J AU Lucast, C Campbell, K Bhatia, S Hodes, R Sanders, V AF Lucast, Christopher Campbell, Kerry Bhatia, Sumeena Hodes, Richard Sanders, Virginia TI Prohibitins and the cytoplasmic domain of CD86 are necessary to mediate signaling in B lymphocytes SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Lucast, Christopher] Ohio State Univ, Integrated Biomed Sci Grad Program, Columbus, OH 43210 USA. [Lucast, Christopher; Sanders, Virginia] Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA. [Campbell, Kerry] Fox Chase Canc Ctr, Inst Canc Res, Philadelphia, PA 19111 USA. [Bhatia, Sumeena; Hodes, Richard] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 109.8 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751704116 ER PT J AU Luckey, M Hong, CW Feigenbaum, L Park, H AF Luckey, Megan Hong, Changwan Feigenbaum, Lionel Park, Hyun TI Suppression of Cytokine Signaling 4 (SOCS4) is a novel immunomodulatory molecule in T cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Luckey, Megan; Hong, Changwan; Park, Hyun] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. [Feigenbaum, Lionel] Sci Applications Int Corp, Lab Anim Sci Program, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 63.14 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751702029 ER PT J AU Lundstrom, W Walsh, S Mackall, C AF Lundstrom, Wangko Walsh, Scott Mackall, Crystal TI Soluble IL7 receptor alpha chain serves as a depot to prevent IL7 consumption SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Lundstrom, Wangko; Mackall, Crystal] NCI, Bethesda, MD 20892 USA. [Walsh, Scott] Univ Maryland Coll Pk, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 57.1 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751701157 ER PT J AU Mage, M Wang, R Boyd, L Revilleza, M Natarajan, K Hansen, T Margulies, D AF Mage, Michael Wang, Rui Boyd, Lisa Revilleza, Maria Natarajan, Kannan Hansen, Ted Margulies, David TI Conformation and solvent-accessibility of an MHC-I alpha-1 domain segment provide insight into the peptide receptive transition state SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Mage, Michael; Wang, Rui; Boyd, Lisa; Revilleza, Maria; Natarajan, Kannan; Margulies, David] NIAID, Mol Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Hansen, Ted] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. [Hansen, Ted] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 100.6 PG 2 WC Immunology SC Immunology GA V44LY UT WOS:000209751703052 ER PT J AU Mage, R Schaffer, A Gertz, E Agarwala, R AF Mage, Rose Schaffer, Alejandro Gertz, E. Agarwala, Richa TI Genes encoding Th2 cytokines and other proteins of immunological interest in the Oryctolagus cuniculus (rabbit) whole genome sequence and ENCODE SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Mage, Rose] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Schaffer, Alejandro; Gertz, E.; Agarwala, Richa] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 170.20 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751708122 ER PT J AU Maravillas-Montero, J Gillespie, P Patino-Lopez, G Shaw, S Santos-Argumedo, L AF Maravillas-Montero, Jose Gillespie, Peter Patino-Lopez, Genaro Shaw, Stephen Santos-Argumedo, Leopoldo TI Myosin 1c participates in B cell cytoskeleton rearrangements, is recruited to the immunological synapse and contributes to antigen presentation. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Maravillas-Montero, Jose; Santos-Argumedo, Leopoldo] IPN, CINVESTAV, Mexico City 07738, DF, Mexico. [Gillespie, Peter] Oregon Hlth & Sci Univ, Oregon Hearing Res Ctr, Portland, OR 97201 USA. [Gillespie, Peter] Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97201 USA. [Patino-Lopez, Genaro; Shaw, Stephen] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 100.48 PG 2 WC Immunology SC Immunology GA V44LY UT WOS:000209751703050 ER PT J AU Marino, AP Murphy, P AF Marino, Ana Paula Murphy, Philip TI Chemoattractant regulation of Toxoplasma gondii-induced encephalitis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Marino, Ana Paula; Murphy, Philip] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 58.4 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751701166 ER PT J AU Marjon, K Lu, JH Marnell, L Wang, RP Mold, C Sun, P Du Clos, T AF Marjon, Kristopher Lu, Jinghua Marnell, Lorraine Wang, Ruipeng Mold, Carolyn Sun, Peter Du Clos, Terry TI Recognition and functional activation of human Fc alpha Rl by C-reactive protein SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Marjon, Kristopher; Mold, Carolyn; Du Clos, Terry] Univ New Mexico, Albuquerque, NM 87131 USA. [Marnell, Lorraine; Du Clos, Terry] VA Med Ctr, Albuquerque, NM USA. [Lu, Jinghua; Wang, Ruipeng; Sun, Peter] NIAID, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 APR PY 2011 VL 186 SU 1 MA 110.22 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751704131 ER PT J AU Massilamany, C Gangaplara, A Gardner, D Steffen, D Somerville, G Reddy, J AF Massilamany, Chandirasegaran Gangaplara, Arunakumar Gardner, Donald Steffen, David Somerville, Greg Reddy, Jay TI TCA cycle inactivation in Staphylococcus aureus alters nitric oxide production in RAW 264.7 cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Massilamany, Chandirasegaran; Gangaplara, Arunakumar; Steffen, David; Somerville, Greg; Reddy, Jay] Univ Nebraska, Lincoln, NE USA. [Gardner, Donald] NIAID, Rocky Mt Vet Branch, Rocky Mt Labs, NIH, Hamilton, MT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 56.21 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751701136 ER PT J AU Mburu, Y Egloff, AM Wang, L Seethala, R Walker, W Van Waes, C Ferris, R AF Mburu, Yvonne Egloff, Ann Marie Wang, Lin Seethala, Raja Walker, William Van Waes, Carter Ferris, Robert TI Regulation of Chemokine Receptor 7 expression by NF-kappa B in Squamous Cell Carcinoma of the Head and Neck SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Mburu, Yvonne; Egloff, Ann Marie; Wang, Lin; Seethala, Raja; Walker, William; Ferris, Robert] Univ Pittsburgh, Immunol, Pittsburgh, PA USA. [Van Waes, Carter] NIDCD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 149.3 PG 2 WC Immunology SC Immunology GA V44LY UT WOS:000209751706017 ER PT J AU McGovern, D Heydari, S AF McGovern, Dorian Heydari, Sara TI B cell immunotherapy to resolve a persistent viral infection SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [McGovern, Dorian; Heydari, Sara] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 53.10 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751701067 ER PT J AU Mello-Coelho, V Cutler, R Tammara, A Bunbury, A Mattson, M Taub, D AF Mello-Coelho, Valeria Cutler, Roy Tammara, Anita Bunbury, Allyson Mattson, Mark Taub, Dennis TI Age-associated alterations of lipid metabolism and oxidative stress in the murine thymus are attenuated by in vivo growth hormone administration SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Mello-Coelho, Valeria; Cutler, Roy; Tammara, Anita; Bunbury, Allyson; Mattson, Mark; Taub, Dennis] NIA, NIH, Baltimore, MD 21224 USA. [Mello-Coelho, Valeria] Univ Fed Rio de Janeiro, Inst Biomed Sci, Rio De Janeiro, Brazil. NR 0 TC 1 Z9 1 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 104.13 PG 2 WC Immunology SC Immunology GA V44LY UT WOS:000209751703165 ER PT J AU Nasholm, N Bouchkouj, N Fry, T Capitini, C AF Nasholm, Nicole Bouchkouj, Najat Fry, Terry Capitini, Christian TI Inhibition of STAT1 modulates GVHD after allogeneic BMT through induction of S100A8/A9 SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Nasholm, Nicole; Bouchkouj, Najat; Fry, Terry; Capitini, Christian] NCI, NIH, Bethesda, MD 20892 USA. [Bouchkouj, Najat] Georgetown Univ, Med Ctr, Washington, DC 20007 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 169.38 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751708103 ER PT J AU Nayak, D Zinselmeyer, B McGavern, D AF Nayak, Debasis Zinselmeyer, Bernd McGavern, Dorian TI Dynamics of an innate myeloid cell response to acute CNS viral infection SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Nayak, Debasis; Zinselmeyer, Bernd; McGavern, Dorian] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 162.16 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751707124 ER PT J AU Olkhanud, P Bodogai, M Wejksza, K Biragyn, A AF Olkhanud, Purevdorj Bodogai, Monica Wejksza, Katarzyna Biragyn, Arya TI Tumor-induced regulatory B cells promote cancer metastasis by inducing generation of FoxP3+regulatory T cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Olkhanud, Purevdorj; Bodogai, Monica; Wejksza, Katarzyna; Biragyn, Arya] NIA, LMBI, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 66.16 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751702150 ER PT J AU Padhan, K Rajat, V AF Padhan, Kartika Rajat, Varma TI Kinetics of c-Fos induction depends upon strength of TCR stimulation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Padhan, Kartika; Rajat, Varma] NIAID, LCMI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 63.13 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751702054 ER PT J AU Park, O Wang, H Weng, HL Li, H Yin, S Feigenbaum, L Ki, SH Yoo, SH Dooley, S Wang, FS Young, H Gao, B AF Park, Ogyi Wang, Hua Weng, Honglei Li, Hai Yin, Shi Feigenbaum, Lionel Ki, Sung-Hwan Yoo, Seong Ho Dooley, Steve Wang, Fu-Sheng Young, Howard Gao, Bin TI In vivo consequences of liver-specific interleukin-22 expression: implications for human liver disease progression SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Park, Ogyi; Wang, Hua; Yin, Shi; Ki, Sung-Hwan; Gao, Bin] NIAAA, Lab Liver Dis, NIH, Rockville, MD 20852 USA. [Weng, Honglei; Dooley, Steve] Heidelberg Univ, Fac Med Mannheim, Med Clin, Mannheim, Germany. [Feigenbaum, Lionel; Young, Howard] NCI, Ctr Canc Res, Frederick, MD 21701 USA. [Li, Hai] Shanghai Jiao Tong Univ, Renji Hosp, Dept Gastroenterol, Shanghai 200030, Peoples R China. [Wang, Fu-Sheng] Beijing Inst Infect Dis, Ctr Clin Lab, Beijing, Peoples R China. [Yoo, Seong Ho] NIAAA, Lab Membrane Biochem & Biophys, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 117.7 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751705118 ER PT J AU Pegu, A Yang, ZY Chen, XJ Todd, JP McKee, K Rao, S Mascola, J Nabel, G AF Pegu, Amarendra Yang, Zhi-yong Chen, Xuejen Todd, John-Paul McKee, Krisha Rao, Srinivas Mascola, John Nabel, Gary TI VRC01 provides sterilizing protection to non human primates from mucosal SHIV challenges SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Pegu, Amarendra; Yang, Zhi-yong; Chen, Xuejen; Todd, John-Paul; McKee, Krisha; Rao, Srinivas; Mascola, John; Nabel, Gary] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 155.11 PG 2 WC Immunology SC Immunology GA V44LY UT WOS:000209751706175 ER PT J AU Pelletier, M Bulua, A Myerowitz-Vanderhoek, S Kastner, D Siegel, R AF Pelletier, Martin Bulua, Ariel Myerowitz-Vanderhoek, Samuel Kastner, Daniel Siegel, Richard TI Predominant role of monocytes rather than neutrophils in the pathogenesis of the familial autoinflammatory disease TRAPS (TNFR-associated Periodic Syndrome) SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Pelletier, Martin; Bulua, Ariel; Myerowitz-Vanderhoek, Samuel; Siegel, Richard] NIAMS, NIH, Bethesda, MD USA. [Kastner, Daniel] NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 54.3 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751701072 ER PT J AU Pinkhasov, J Lee, J El-Khoury, D Lee, L Hwang, S Lesourne, R Zhang, YQ Weng, NP Love, P AF Pinkhasov, Julia Lee, Jan El-Khoury, Dalal Lee, LiQi Hwang, SuJin Lesourne, Renaud Zhang, Yongqing Weng, Nan-Ping Love, Paul TI Identifying molecules that "fine-tune" T cell antigen receptor signaling during thymocyte selection SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Pinkhasov, Julia; Lee, Jan; El-Khoury, Dalal; Lee, LiQi; Hwang, SuJin; Lesourne, Renaud; Love, Paul] NICHD, NIH, Bethesda, MD USA. [Zhang, Yongqing; Weng, Nan-Ping] NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 64.5 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751702057 ER PT J AU Pinto, L Kemp, T Hildesheim, A Safaeian, M Pan, YJ Porras, C Schiller, J Lowy, D Rolando, H AF Pinto, Ligia Kemp, Troy Hildesheim, Allan Safaeian, Mahboobeh Pan, Yuanji Porras, Carolina Schiller, John Lowy, Douglas Rolando, Herrero TI Bivalent HPV16/18 L1 VLP vaccine induces cross-neutralizing antibodies that may mediate cross-protection SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Pinto, Ligia; Kemp, Troy; Pan, Yuanji] NCI Frederick, SAIC Frederick, Frederick, MD USA. [Hildesheim, Allan; Safaeian, Mahboobeh; Schiller, John; Lowy, Douglas] NIH, Bethesda, MD 20892 USA. [Porras, Carolina; Rolando, Herrero] Proyecto Epidemiol Guanacaste, San Jose, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 155.27 PG 2 WC Immunology SC Immunology GA V44LY UT WOS:000209751706188 ER PT J AU Pisitkun, P Ha, HL Claudio, E Tivy, C Wang, HS Siebenlist, U AF Pisitkun, Prapaporn Ha, Hye-Lin Claudio, Estefania Tivy, Caitlyn Wang, Hongshan Siebenlist, Ulrich TI Loss of CIKS/Act1, the signaling adaptor for IL-17 family cytokines, significantly ameliorates development of fatal disease in the Fcgamma RIIB-deficient mouse model for lupus SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Pisitkun, Prapaporn; Ha, Hye-Lin; Claudio, Estefania; Tivy, Caitlyn; Wang, Hongshan; Siebenlist, Ulrich] NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 101.18 PG 2 WC Immunology SC Immunology GA V44LY UT WOS:000209751703119 ER PT J AU Punkosdy, G Shevach, E AF Punkosdy, George Shevach, Ethan TI Regulatory T cells suppress immune activation under homeostatic conditions in adult mice by antigen-independent and -dependent mechanisms SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Punkosdy, George; Shevach, Ethan] NIAID, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 168.22 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751708063 ER PT J AU Qiu, XG Lisa, F Alimonti, J Feldmann, H Kobinger, G Jones, S AF Qiu, Xiangguo Lisa, Fernando Alimonti, Judie Feldmann, Heinz Kobinger, Gary Jones, Steven TI Anti-Ebola GP monoclonal antibodies protect mice and guinea pigs against lethal ebola virus challenge SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Qiu, Xiangguo; Lisa, Fernando; Alimonti, Judie; Kobinger, Gary] Publ Hlth Agcy Canada, Natl Microbiol Lab, Special Pathogens Program, Winnipeg, MB, Canada. [Kobinger, Gary; Jones, Steven] Univ Manitoba, Dept Immunol, Winnipeg, MB, Canada. [Alimonti, Judie; Kobinger, Gary; Jones, Steven] Univ Manitoba, Dept Microbiol, Winnipeg, MB R3T 2N2, Canada. [Feldmann, Heinz] NIH, Hamilton, MT USA. NR 0 TC 0 Z9 0 U1 2 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 APR PY 2011 VL 186 SU 1 MA 105.29 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751704004 ER PT J AU Ramalingam, T Barron, L Mentink-Kane, M Cheever, A Humbles, A Kolbeck, R Wynn, T AF Ramalingam, Thirumalai Barron, Luke Mentink-Kane, Margaret Cheever, Allen Humbles, Alison Kolbeck, Roland Wynn, Thomas TI Augmented Th2 response and liver fibrosis in mice lacking the chitinase like protein, BRP-39 SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Ramalingam, Thirumalai; Barron, Luke; Mentink-Kane, Margaret; Wynn, Thomas] NIAID, LPD, Bethesda, MD 20892 USA. [Humbles, Alison; Kolbeck, Roland] Medimmune, Gaithersburg, MD USA. [Cheever, Allen] Biomed Res Inst, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 58.9 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751701172 ER PT J AU Ramaswamy, M Do, T Cora-Morges, A Cruz, A Siegel, R AF Ramaswamy, Madhu Thao Do Cora-Morges, Adrian Cruz, Anthony Siegel, Richard TI Early signaling events regulate Fas-induced apoptosis in CD4+T cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Ramaswamy, Madhu; Thao Do; Cora-Morges, Adrian; Cruz, Anthony; Siegel, Richard] NIAMS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 APR PY 2011 VL 186 SU 1 MA 104.5 PG 2 WC Immunology SC Immunology GA V44LY UT WOS:000209751703175 ER PT J AU Revilleza, MJ Mans, J Iizuka, K Mage, M Carey, R Boyd, L Natarajan, K Margulies, D AF Revilleza, Maria Jamela Mans, Janet Iizuka, Koho Mage, Michael Carey, Rosalene Boyd, Lisa Natarajan, Kannan Margulies, David TI Recognition of a dendritic cell ligand by an MCMV-encoded MHC-I-like protein SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Revilleza, Maria Jamela; Mage, Michael; Carey, Rosalene; Boyd, Lisa; Natarajan, Kannan; Margulies, David] NIH, Bethesda, MD 20892 USA. [Mans, Janet] Univ Pretoria, Pretoria, South Africa. [Iizuka, Koho] Univ Minnesota, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 154.17 PG 2 WC Immunology SC Immunology GA V44LY UT WOS:000209751706171 ER PT J AU Roffe, E Santiago, H Lionakis, M Barber, D Murphy, P AF Roffe, Ester Santiago, Helton Lionakis, Michail Barber, Daniel Murphy, Philip TI Ccr7 is critical for resistance against experimental Trypanosoma cruzi infection SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Roffe, Ester; Lionakis, Michail; Murphy, Philip] NIAID, LMI, NIH, Bethesda, MD 20892 USA. [Santiago, Helton; Barber, Daniel] NIAID, LPD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 56.4 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751701120 ER PT J AU Santiago, M Smith, D Barrett, B Guo, KJ Heilman, K Benitez, R Montano, M Pelanda, R Hasenkrug, K Greene, W AF Santiago, Mario Smith, Diana Barrett, Bradley Guo, Kejun Heilman, Karl Benitez, Robert Montano, Mauricio Pelanda, Roberta Hasenkrug, Kim Greene, Warner TI Unraveling how Rfv3/Apobec3 promotes the retrovirus-specific neutralizing antibody response SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Santiago, Mario; Smith, Diana; Barrett, Bradley; Guo, Kejun; Heilman, Karl] Univ Colorado Denver, ID Div, Aurora, CO USA. [Benitez, Robert; Montano, Mauricio; Greene, Warner] Gladstone Inst Virol & Immunol, San Francisco, CA USA. [Pelanda, Roberta] Natl Jewish Hlth, Denver, CO USA. [Hasenkrug, Kim] NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 105.12 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751704022 ER PT J AU Savan, R Legiewicz, M McFarland, A Schwerk, J Bindewald, E Orr, S Ramakrishnan, K Yalamanchili, R Kronfli, A McVicar, D Carrington, M Anderson, S Shapiro, B LeGrice, S Young, H AF Savan, Ram Legiewicz, Michal McFarland, Adelle Schwerk, Johannes Bindewald, Eckart Orr, Selinda Ramakrishnan, Karthika Yalamanchili, Rajesh Kronfli, Anthony McVicar, Daniel Carrington, Mary Anderson, Stephen Shapiro, Bruce LeGrice, Stuart Young, Howard TI MicroRNA-29 stabilizes interferon-gamma mRNA by antagonizing AU-rich element-mediated decay SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Savan, Ram; Legiewicz, Michal; McFarland, Adelle; Schwerk, Johannes; Bindewald, Eckart; Orr, Selinda; Ramakrishnan, Karthika; Yalamanchili, Rajesh; Kronfli, Anthony; McVicar, Daniel; Carrington, Mary; Anderson, Stephen; Shapiro, Bruce; LeGrice, Stuart; Young, Howard] NCI, Frederick, MD 21701 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 57.3 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751701143 ER PT J AU Schneider, E Gaur, S Murphy, P Gao, JL AF Schneider, Erich Gaur, Sonia Murphy, Philip Gao, Ji-Liang TI Formyl peptide receptor 1 is functionally expressed on human lens epithelial cells and promotes lens homeostasis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Schneider, Erich; Gaur, Sonia; Murphy, Philip; Gao, Ji-Liang] NIAID, Lab Mol Immunol, Mol Signalling Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 149.19 PG 2 WC Immunology SC Immunology GA V44LY UT WOS:000209751706007 ER PT J AU Shen, W Li, WQ Feigenbaum, L Hixon, J Durum, S AF Shen, Wei Li, Wenqing Feigenbaum, Lionel Hixon, Julie Durum, Scott TI Differential expression of IL-17A and Il-17F in inflammatory bowel disease/colon cancer using a new IL-17A/F-dual-color reporter mouse SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Shen, Wei; Li, Wenqing; Hixon, Julie; Durum, Scott] NCI, LMI, CIP, CCR,NIH, Frederick, MD 21701 USA. [Feigenbaum, Lionel] NCI, LASP, CCR, NIH, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 114.1 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751705042 ER PT J AU Sklavos, M Zhu, ZG Singh, V Hurwitz, A AF Sklavos, Martha Zhu, Zigiang Singh, Vinod Hurwitz, Arthur TI High avidity T cells have increased potential to convert to FoxP3+T cells in vitro and in the tumor microenvironment SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Sklavos, Martha; Zhu, Zigiang; Singh, Vinod; Hurwitz, Arthur] NCI, CCR, CIP, LMI,NIH, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 156.29 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751707016 ER PT J AU Smrz, D Kim, MS Silhankova, S Wilson, T Metcalfe, D Gilfillan, A AF Smrz, Daniel Kim, Mi-Sun Silhankova, Sarka Wilson, Todd Metcalfe, Dean Gilfillan, Alasdair TI MTORC1 and mTORC2 control normal and neoplastic mast cell homoeostasis through regulation of cell division rather than maintenance of survival SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Smrz, Daniel; Kim, Mi-Sun; Silhankova, Sarka; Wilson, Todd; Metcalfe, Dean; Gilfillan, Alasdair] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 151.20 PG 2 WC Immunology SC Immunology GA V44LY UT WOS:000209751706045 ER PT J AU Stewart, C Metheny, H Dzutsev, A Karp, C Trinchieri, G AF Stewart, Charles Metheny, Hannah Dzutsev, Amiran Karp, Christopher Trinchieri, Giorgio TI STAT1 and IFNAR1 regulate Treg frequencies and IL-10 expression the tumor microenvironment SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Stewart, Charles; Metheny, Hannah; Dzutsev, Amiran; Trinchieri, Giorgio] NCI, Canc & Inflammat Program, CCR, Frederick, MD 21701 USA. [Karp, Christopher] Cincinnati Childrens Hosp Res Fdn, Cincinnati, OH USA. [Karp, Christopher] Univ Cincinnati, Coll Med, Cincinnati, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 66.15 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751702125 ER PT J AU Subedl, K Araki, Y De, S Wood, W Sharov, A Zang, CZ Schones, D Lhotsky, B Dudekula, D Becker, K Ko, MR Peng, WQ Zhao, KJ Weng, NP AF Subedl, Kalpana Araki, Yasuto De, Supriyo Wood, William Sharov, Alexei Zang, Chongzhi Schones, Dustin Lhotsky, Brad Dudekula, Dawood Becker, Kevin Ko, Minoru Peng, Weiqun Zhao, Keji Weng, Nan-ping TI Dynamic changes of gene expression in concordance with histone modifications in CD8 T cells after activation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Subedl, Kalpana; Araki, Yasuto; Weng, Nan-ping] NIA, Lab Mol Biol & Immunol, Baltimore, MD 21224 USA. [De, Supriyo; Wood, William; Becker, Kevin] NIA, Gene Express & Genom Unit, Baltimore, MD 21224 USA. [Sharov, Alexei; Dudekula, Dawood; Ko, Minoru] NIA, Lab Genet, Baltimore, MD 21224 USA. [Zang, Chongzhi; Peng, Weiqun] George Washington Univ, Dept Phys, Washington, DC 20052 USA. [Schones, Dustin; Zhao, Keji] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Lhotsky, Brad] NIA, IT Sect, Baltimore, MD 21224 USA. RI Zang, Chongzhi/D-1445-2011 NR 0 TC 0 Z9 0 U1 1 U2 1 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 APR PY 2011 VL 186 SU 1 MA 159.2 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751707056 ER PT J AU Tan, CY Vistica, B Nugent, L Zureick, A Shi, GP Gery, I AF Tan, Cuiyan Vistica, Barbara Nugent, Lindsey Zureick, Andrew Shi, Guangpu Gery, Igal TI Two distinct Th9 subpopulations are generated by activating naive CD4 cells with either antigen/APC, or anti-CD3/CD28 antibodies SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Tan, Cuiyan; Vistica, Barbara; Nugent, Lindsey; Zureick, Andrew; Shi, Guangpu; Gery, Igal] NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 152.12 PG 2 WC Immunology SC Immunology GA V44LY UT WOS:000209751706084 ER PT J AU Tewary, P dela Rosa, G Rodriguez, L Riboldi, E Shirota, H Patrek, K Klinman, D Yang, D Oppenheim, J AF Tewary, Poonam dela Rosa, Gonzalo Rodriguez, Luis Riboldi, Elena Shirota, Hidekazu Patrek, Karel Klinman, Dennis Yang, De Oppenheim, Joost TI Lactoferrin inhibits DNA-induced IFN-alpha production by human plasmacytoid dendritic cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Tewary, Poonam; dela Rosa, Gonzalo; Riboldi, Elena; Oppenheim, Joost] NCI, LMI, CIP, Frederick, MD 21701 USA. [Shirota, Hidekazu; Klinman, Dennis] NCI, LEI, CIP, Frederick, MD 21701 USA. [Yang, De] SAIC NCI, BRP, LMI, Frederick, MD USA. [Rodriguez, Luis] SAIC NCI, Image Anal Lab, Frederick, MD USA. [Patrek, Karel] Aggenix Inc, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 111.4 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751704175 ER PT J AU Tsourkas, P Liu, WL Das, S Pierce, S Raychaudhuri, S AF Tsourkas, Philippos Liu, Wanli Das, Somkanya Pierce, Susan Raychaudhuri, Subhadip TI Discrimination of membrane antigen affinity by B cells requires dominance of kinetic proofreading over serial triggering SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Tsourkas, Philippos; Das, Somkanya; Raychaudhuri, Subhadip] Univ Calif Davis, Davis, CA 95616 USA. [Liu, Wanli; Pierce, Susan] NIAID, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 112.10 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751704198 ER PT J AU Vagida, M Pobezinsky, L Pobezinskaya, E Kazansky, D AF Vagida, Murad Pobezinsky, Leonid Pobezinskaya, Elena Kazansky, Dmitry TI Intrathymic cortisone-resistant memory cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Vagida, Murad; Kazansky, Dmitry] NN Blokhin Canc Res Ctr, Carcinogenesis Inst, Lab Regulatory Mech Immun, Moscow, Russia. [Pobezinsky, Leonid; Pobezinskaya, Elena] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 46.11 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751700068 ER PT J AU Voynova, E Bolland, S AF Voynova, Elisaveta Bolland, Silvia TI Role of interferon-producing killer dendritic cells in the development of autoimmune disease SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Voynova, Elisaveta; Bolland, Silvia] NIAID, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 44.14 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751700018 ER PT J AU Wan, FY Lenardo, M AF Wan, Fengyi Lenardo, Michael TI Phosphorylation regulates RPS3-conferred specific NF-kappa B signaling during foodborne pathogen infection SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Wan, Fengyi] Johns Hopkins Univ, Baltimore, MD USA. [Wan, Fengyi; Lenardo, Michael] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 110.7 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751704134 ER PT J AU Wan, WZ Lim, J Lionakis, M Rivollier, A McDermott, D Kelsall, B Farber, J Murphy, P AF Wan, Wuzhou Lim, Jean Lionakis, Michail Rivollier, Aymeric McDermott, David Kelsall, Brian Farber, Joshua Murphy, Philip TI Genetic deletion of chemokine receptor Ccr6 decreases atherogenesis in ApoE-deficient mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Wan, Wuzhou; Lim, Jean; Lionakis, Michail; Rivollier, Aymeric; McDermott, David; Kelsall, Brian; Farber, Joshua; Murphy, Philip] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 117.2 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751705138 ER PT J AU Watanabe, M Bhatia, S Hodes, R AF Watanabe, Masashi Bhatia, Sumeena Hodes, Richard TI The generation of a B7 conditional knockout mouse SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Watanabe, Masashi; Bhatia, Sumeena; Hodes, Richard] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 63.27 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751702032 ER PT J AU Watkins, S Zhu, ZQ Ambs, S Hurwitz, A AF Watkins, Stephanie Zhu, Ziqiang Ambs, Stefan Hurwitz, Arthur TI Identification of FOXO3A as a regulator of dendritic cell tolerogenicity in human and murine prostate cancer SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Watkins, Stephanie; Zhu, Ziqiang; Hurwitz, Arthur] NCI, Frederick, MD 21701 USA. [Ambs, Stefan] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 165.22 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751707186 ER PT J AU Weinstein, J Poholek, A Hernandez, S Nowyhead, H Bertino, S Craft, J AF Weinstein, Jason Poholek, Amanda Hernandez, Sairy Nowyhead, Heba Bertino, Sarah Craft, Joseph TI Upregulation of Bcl6 expression in Follicular Helper T cells (TFH) requires both dendritic and antigen-specific B cell help. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Weinstein, Jason; Hernandez, Sairy; Nowyhead, Heba; Bertino, Sarah; Craft, Joseph] Yale Univ, Rheumatol, New Haven, CT USA. [Poholek, Amanda] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 63.10 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751702028 ER PT J AU Williams, J Jenkinson, R Zhang, JJ Xie, P Bishop, G Hollaender, G Hodes, R AF Williams, Joy Jenkinson, Rhiannon Zhang, Jingjing Xie, Ping Bishop, Gail Hollaender, Georg Hodes, Richard TI Activation of the non-classical NF-kB pathway in thymic epithelial cells drives mTEC development in the absence of TCR plus thymocytes SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Williams, Joy; Jenkinson, Rhiannon; Zhang, Jingjing] NCI, Expt Immunl Branch, NIH, Bethesda, MD 20892 USA. [Xie, Ping] Rutgers State Univ, Dept Cell Biol & Neurosci, Piscataway, NJ USA. [Bishop, Gail] Univ Iowa, Dept Microbiol, Iowa City, IA 52242 USA. [Hollaender, Georg] Univ Basel, Lab Pediat Immunol, Basel, Switzerland. [Hollaender, Georg] Univ Childrens Hosp, Basel, Switzerland. [Hodes, Richard] NIA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 64.14 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751702063 ER PT J AU Yang, D Postnikov, Y Li, YN Tewary, P de la Rosa, G Kliman, D Furusawa, T Bustin, M Wei, F Oppenheim, J AF Yang, De Postnikov, Yuri Li, Yana Tewary, Poonam de la Rosa, Gonzalo Kliman, Dennis Furusawa, Takashi Bustin, Michael Wei, Feng Oppenheim, Joost TI High mobility group nucleosome-binding protein 1 acts as an alarmin critical for the induction of immune response SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Yang, De] SAIC Frederick, Frederick, MD USA. [Yang, De; Li, Yana; Tewary, Poonam; de la Rosa, Gonzalo; Kliman, Dennis; Wei, Feng; Oppenheim, Joost] NCI, Frederick, MD 21701 USA. [Postnikov, Yuri; Furusawa, Takashi; Bustin, Michael] NCI, NIH, Bethesda, MD 20892 USA. RI Bustin, Michael/G-6155-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 113.7 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751705033 ER PT J AU Yin, H Nguyen, C Samani, Y Uede, T Peck, A Chiorini, J AF Yin, Hongen Cuong Nguyen Samani, Yuval Uede, Toshimitsu Peck, Ammon Chiorini, John TI Prevention of murine Sjogren's syndrome by local delivery of adeno-associated virus mediated Cytotoxic T-Lymphocyte Antigen 4-immunoglobulin G fusion protein SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Yin, Hongen; Samani, Yuval; Chiorini, John] NIH, Bldg 10, Bethesda, MD 20892 USA. [Cuong Nguyen; Peck, Ammon] Univ Florida, Gainesville, FL USA. [Uede, Toshimitsu] Hokkaido Univ, Sapporo, Hokkaido, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 107.1 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751704063 ER PT J AU Yin, HG Vosters, J Roescher, N D'Souza, A Kurien, B Tak, P Chiorini, J AF Yin, Hongen Vosters, Jelle Roescher, Nienke D'Souza, Anil Kurien, Biji Tak, Paul Chiorini, John TI Location of immunization and interferon-gamma are central to induction of salivary gland dysfunction in Ro60 peptide immunized model of Sjogren's syndrome SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Yin, Hongen; Chiorini, John] NIH, Bethesda, MD 20892 USA. [Vosters, Jelle; Roescher, Nienke; Tak, Paul] Univ Amsterdam, Amsterdam, Netherlands. [D'Souza, Anil; Kurien, Biji] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 101.25 PG 2 WC Immunology SC Immunology GA V44LY UT WOS:000209751703105 ER PT J AU Zhang, H Galli, S Mackall, C AF Zhang, Hua Galli, Susana Mackall, Crystal TI A novel subset of myeloid suppressor cells in pediatric cancer patients SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Zhang, Hua; Galli, Susana; Mackall, Crystal] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 66.9 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751702160 ER PT J AU Zheng, WJ Crampton, S Bolland, S AF Zheng, Wenjie Crampton, Steve Bolland, Silvia TI Toll-like receptor3 overexpression alters responses to toll-like receptorl ligand SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Zheng, Wenjie; Crampton, Steve; Bolland, Silvia] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 111.6 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751704179 ER PT J AU Zinselmeyer, B Heydari, S Nayak, D McGavern, D AF Zinselmeyer, Bernd Heydari, Sara Nayak, Debasis McGavern, Dorian TI 2P imaging reveals that PD-1 blockade promotes clearance of a persistent viral infection by overriding prolonged T cell engagement SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Zinselmeyer, Bernd; Heydari, Sara; Nayak, Debasis; McGavern, Dorian] NINDS, Viral Immunobiol & Intravital Imaging Unit, NINDS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 2011 VL 186 SU 1 MA 154.18 PG 2 WC Immunology SC Immunology GA V44LY UT WOS:000209751706138 ER PT J AU Chaturvedi, AK Katki, HA Hildesheim, A Rodriguez, AC Quint, W Schiffman, M Van Doorn, LJ Porras, C Wacholder, S Gonzalez, P Sherman, ME Herrero, R AF Chaturvedi, Anil K. Katki, Hormuzd A. Hildesheim, Allan Cecilia Rodriguez, Ana Quint, Wim Schiffman, Mark Van Doorn, Leen-Jan Porras, Carolina Wacholder, Sholom Gonzalez, Paula Sherman, Mark E. Herrero, Rolando CA CVT Grp TI Human Papillomavirus Infection with Multiple Types: Pattern of Coinfection and Risk of Cervical Disease SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID NONVACCINE HPV TYPES; AGED 16-26 YEARS; 18 DNA LOAD; PARTICLE VACCINE; POOLED ANALYSIS; CLINICAL-TRIAL; DOUBLE-BLIND; COSTA-RICA; WOMEN; ACQUISITION AB Objective. We investigated coinfection patterns for 25 human papillomavirus (HPV) types and assessed the risk conferred by multiple HPV types toward cervical disease. Methods. Sexually active women (n=5,871) in the NCI-sponsored Costa Rica HPV Vaccine Trial's prevaccination enrollment visit were analyzed. Genotyping for 25 HPVs was performed using SPF(10)/LiPA(25). We calculated odds ratios (ORs) to assess coinfection patterns for each genotype with 24 other genotypes. These ORs were pooled and compared with pair-specific ORs to identify genotype combinations that deviated from the pooled OR. We compared risk of CIN2+/HSIL+between multiple and single infections and assessed additive statistical interactions. Results. Of the 2478 HPV-positive women, 1070 (43.2%) were infected with multiple types. Multiple infections occurred significantly more frequently than predicted by chance. However, this affinity to be involved in a coinfection (pooled OR for 300 type-type combinations=2.2; 95% confidence interval [CI]=2.1-2.4) was not different across HPV type-type combinations. Compared with single infections, coinfection with multiple alpha 9 species was associated with significantly increased risk of CIN2+(OR=2.2; 95% CI=1.1-4.6) and HSIL+(OR=1.6; 95% CI=1.1-2.4). However, disease risk was similar to the sum of estimated risk from individual types, with little evidence for synergistic interactions. Conclusions. Coinfecting HPV genotypes occur at random and lead to cervical disease independently. C1 [Chaturvedi, Anil K.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. [Cecilia Rodriguez, Ana; Porras, Carolina; Gonzalez, Paula; Herrero, Rolando] Fdn INCIENSA, Proyecto Epidemiol Guanacaste, Liberia, Costa Rica. [Quint, Wim; Van Doorn, Leen-Jan] DDL Diagnost Lab, Voorburg, Netherlands. RP Chaturvedi, AK (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS 7072, Rockville, MD 20852 USA. EM chaturva@mail.nih.gov RI Katki, Hormuzd/B-4003-2015; Hildesheim, Allan/B-9760-2015; Chaturvedi, Anil/J-2024-2015 OI Hildesheim, Allan/0000-0003-0257-2363; Chaturvedi, Anil/0000-0003-2696-8899 FU National Cancer Institute (NCI) [N01-CP-11005]; NIH Office for Research on Women's Health FX The Costa Rican Vaccine Trial (CVT) is a longstanding collaboration between investigators in Costa Rica and Intramural Research Program (IRP) of the National Cancer Institute (NCI). The CVT trial is sponsored and funded by NCI (N01-CP-11005) with support from the NIH Office for Research on Women's Health and conducted in agreement with the Ministry of Health of Costa Rica. Vaccine was provided for CVT by GSK Biologicals, under a Clinical Trials Agreement with NCI. GSK also provided support for aspects of the trial associated with regulatory submission needs of the company under FDA BB-IND 7920. Douglas Lowy and John Schiller from NCI are named inventors on U.S.-government owned HPV vaccine patents that are licensed to GSK and Merck, and so are entitled to limited royalties as specified by federal law. NR 29 TC 87 Z9 94 U1 0 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR 1 PY 2011 VL 203 IS 7 BP 910 EP 920 DI 10.1093/infdis/jiq139 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 737FF UT WOS:000288553800005 PM 21402543 ER PT J AU Chen, GL Min, JY Lamirande, EW Santos, C Jin, H Kemble, G Subbarao, K AF Chen, Grace L. Min, Ji-Young Lamirande, Elaine W. Santos, Celia Jin, Hong Kemble, George Subbarao, Kanta TI Comparison of a Live Attenuated 2009 H1N1 Vaccine with Seasonal Influenza Vaccines against 2009 Pandemic H1N1 Virus Infection in Mice and Ferrets SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID A H1N1; TEMPERATURE SENSITIVITY; INACTIVATED VACCINES; CANDIDATE VACCINES; PROTECTION; TRIVALENT; IMMUNITY; PREVENTION; HUMANS; MODEL AB The role of seasonal influenza vaccination in pandemic influenza A H1N1 disease is important to address, because a large segment of the population is vaccinated annually. We administered 1 or 2 doses of pandemic H1N1 vaccine (CA/7 ca), a seasonal trivalent inactivated (s-TIV), or live attenuated influenza vaccine (s-LAIV) to mice and ferrets and subsequently challenged them with a pandemic H1N1 virus. In both species, CA/7 ca was immunogenic and conferred complete protection against challenge. s-TIV did not confer protection in either animal model, and s-LAIV did not confer any protection in ferrets. In mice, 2 doses of s-LAIV led to complete protection in the upper respiratory tract and partial protection in the lungs. Our data indicate that vaccination with the seasonal influenza vaccines did not confer complete protection in the lower respiratory tract in either animal model, whereas the CA/7 ca vaccine conferred complete protection in both animal models. C1 [Chen, Grace L.; Min, Ji-Young; Lamirande, Elaine W.; Santos, Celia; Subbarao, Kanta] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Jin, Hong; Kemble, George] MedImmune, Mountain View, CA USA. RP Subbarao, K (reprint author), NIAID, Infect Dis Lab, NIH, 33 N Dr,MSC 3203,Rm 3E 13C 1, Bethesda, MD 20892 USA. EM ksubbarao@niaid.nih.gov FU National Institutes of Health and the National Institute of Allergy and Infectious Diseases (NIAID) FX This work was supported in part by the Intramural Research Program of the National Institutes of Health and the National Institute of Allergy and Infectious Diseases (NIAID). This research was performed as part of a Cooperative Research and Development Agreement between the Laboratory of Infectious Diseases, NIAID and MedImmune. NR 32 TC 22 Z9 22 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR 1 PY 2011 VL 203 IS 7 BP 930 EP 936 DI 10.1093/infdis/jiq144 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 737FF UT WOS:000288553800007 PM 21257740 ER PT J AU An, P Winkler, C Guan, L O'Brien, SJ Zeng, Z AF An, Ping Winkler, Cheryl Guan, Li O'Brien, Stephen J. Zeng, Zheng CA HBV Study Consortium TI A Common HLA-DPA1 Variant is a Major Determinant of Hepatitis B Virus Clearance in Han Chinese SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HEPATOCELLULAR-CARCINOMA; HBSAG SEROCLEARANCE; CARRIERS; ASSOCIATION; INFECTION AB A recent genome-wide study showed that the single nucleotide polymorphisms (SNPs) in the HLA-DP region were associated with chronic hepatitis B virus (HBV) infection in Japanese and Thai persons. We tested the effects of HLA-DP SNPs for all major HBV outcomes in Han Chinese (n = 1742): HBV resistance, clearance, chronic infection, cirrhosis, and hepatocellular carcinoma. HLA - DPA1 rs3077 T was strongly associated with decreased risk of chronic HBV infection (odds ratio, .62; P = .001), consistent with the previous report. We showed for the first time to our knowledge that it is a predictor for HBV clearance (odds ratio, 2.41; P < .001). However, rs3077 was not associated with the development of cirrhosis or hepatocellular carcinoma. C1 [An, Ping; Winkler, Cheryl] NCI, Basic Res Lab, Frederick, MD 21702 USA. [Guan, Li] NCI, Lab Genom Divers, SAIC Frederick, Frederick, MD 21702 USA. [Zeng, Zheng] Peking Univ, Dept Infect Dis, Hosp 1, Beijing 100871, Peoples R China. RP An, P (reprint author), NCI, Basic Res Lab, Bldg 560,Rm 21-19, Frederick, MD 21702 USA. EM Ping.An@nih.gov; zeng@bjmu.edu.cn FU National Cancer Institue, National Institutes of Health [HHSN26120080001E]; National Institutes of Health, National Cancer Institute, Center for Cancer Research FX This work was supported in whole or in part with federal funds from the National Cancer Institue, National Institutes of Health (HHSN26120080001E), and the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 15 TC 37 Z9 41 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR 1 PY 2011 VL 203 IS 7 BP 943 EP 947 DI 10.1093/infdis/jiq154 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 737FF UT WOS:000288553800009 PM 21402545 ER PT J AU Li, JZ Brumme, ZL Brumme, CJ Wang, HY Spritzler, J Robertson, MN Lederman, MM Carrington, M Walker, BD Schooley, RT Kuritzkes, DR AF Li, Jonathan Z. Brumme, Zabrina L. Brumme, Chanson J. Wang, Hongying Spritzler, John Robertson, Michael N. Lederman, Michael M. Carrington, Mary Walker, Bruce D. Schooley, Robert T. Kuritzkes, Daniel R. CA AIDS Clinical Trials Grp A5197 TI Factors Associated With Viral Rebound in HIV-1-Infected Individuals Enrolled in a Therapeutic HIV-1 gag Vaccine Trial SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; T-CELL RESPONSES; CLASS-I; DISEASE PROGRESSION; ESCAPE MUTATIONS; IMMUNE-RESPONSES; INFECTION; HLA; LOAD; VIREMIA AB Background. Human immunodeficiency virus type 1 (HIV-1) vaccines directed to the cell-mediated immune system could have a role in lowering the plasma HIV-1 RNA set point, which may reduce infectivity and delay disease progression. Methods. Randomized, placebo-controlled trial involving HIV-1-infected participants who received a recombinant adenovirus serotype 5 (rAd5) HIV-1 gag vaccine or placebo. Sequence-based HLA typing was performed for all 110 participants who initiated analytic treatment interruption (ATI) to assess the role of HLA types previously associated with HIV prognosis. Plasma HIV-1 gag and pol RNA sequences were obtained during the ATI. Virologic endpoints and HLA groups were compared between treatment arms using the 2-sample rank sum test. A linear regression model was fitted to derive independent correlates of ATI week 16 plasma viral load (w16 PVL). Results. Vaccinated participants with neutral HLA alleles had lower median w16 PVLs than did vaccinated participants with protective HLA alleles (P = .01) or placebo participants with neutral HLA alleles (P = .02). Factors independently associated with lower w16 PVL included lower pre-antiretroviral therapy PVL, greater Gag sequence divergence from the vaccine sequence, decreased proportion of HLA-associated polymorphisms in Gag, and randomization to the vaccine arm. Conclusions. Therapeutic vaccination with a rAd5-HIV gag vaccine was associated with lower ATI week 16 PVL even after controlling for viral and host genetic factors. C1 [Li, Jonathan Z.; Kuritzkes, Daniel R.] Brigham & Womens Hosp, Sect Retroviral Therapeut, Cambridge, MA 02139 USA. [Li, Jonathan Z.; Walker, Bruce D.; Kuritzkes, Daniel R.] Harvard Univ, Sch Med, Boston, MA USA. [Brumme, Zabrina L.; Brumme, Chanson J.; Carrington, Mary; Walker, Bruce D.] MIT, Massachusetts Gen Hosp, Ragon Inst, Cambridge, MA 02139 USA. [Brumme, Zabrina L.; Brumme, Chanson J.; Carrington, Mary; Walker, Bruce D.] Harvard Univ, Cambridge, MA 02138 USA. [Brumme, Zabrina L.] Simon Fraser Univ, Burnaby, BC V5A 1S6, Canada. [Wang, Hongying; Spritzler, John] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Robertson, Michael N.] Merck Res Labs, N Wales, PA USA. [Lederman, Michael M.] Case Western Reserve Univ, Div Infect Dis, Cleveland, OH 44106 USA. [Carrington, Mary] NCI Frederick, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick Inc, Frederick, MD USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Schooley, Robert T.] Univ Calif San Diego, Div Infect Dis, La Jolla, CA 92093 USA. RP Kuritzkes, DR (reprint author), Brigham & Womens Hosp, Sect Retroviral Therapeut, 65 Landsdowne St,Rm 449, Cambridge, MA 02139 USA. EM dkuritzkes@partners.org OI Brumme, Chanson/0000-0003-2722-5288 FU Canadian Institutes of Health Research; Intramural NIH HHS; NCRR NIH HHS [K24 RR016482]; NIAID NIH HHS [P30 AI60354, U01 AI068636, P30 AI060354, T32 AI007387, T32 AI07387, U01 AI068634]; PHS HHS [HHSN261200800001E] NR 43 TC 15 Z9 16 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR 1 PY 2011 VL 203 IS 7 BP 976 EP 983 DI 10.1093/infdis/jiq143 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 737FF UT WOS:000288553800013 PM 21402549 ER PT J AU Morasso, MI AF Morasso, Maria I. TI The Influence of Flightless I: Regeneration versus Wound Healing SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Editorial Material ID REGULATOR; REPAIR AB The molecular mechanisms involved in organ regeneration has biomedical implications in regenerative medicine. In this issue, Waters et al. demonstrate that levels of the established negative wound healing factor Flightless I (Flii) modulate the hair follicle's capacity to regenerate a fiber-forming bulb after amputation. Still to be investigated are the specific pathways through which Flii influences regeneration as compared with wound healing. Journal of Investigative Dermatology (2011) 131, 816-817. doi:10.1038/jid.2011.8 C1 NIAMSD, Dev Skin Biol Sect, NIH, Bethesda, MD 20892 USA. RP Morasso, MI (reprint author), NIAMSD, Dev Skin Biol Sect, NIH, Bldg 50,Room 7525, Bethesda, MD 20892 USA. EM morassom@mail.nih.gov FU Intramural NIH HHS NR 8 TC 0 Z9 1 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2011 VL 131 IS 4 BP 816 EP 817 DI 10.1038/jid.2011.8 PG 2 WC Dermatology SC Dermatology GA 743RG UT WOS:000289035800007 PM 21407235 ER PT J AU Kuschal, C DiGiovanna, JJ Khan, SG Kraemer, KH AF Kuschal, C. DiGiovanna, J. J. Khan, S. G. Kraemer, K. H. TI Increased DNA repair in xeroderma pigmentosum group C cells by induction of readthrough of stop codons SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2011 CL Phoenix, AZ SP Soc Investigat Dermatol C1 [Kuschal, C.; DiGiovanna, J. J.; Khan, S. G.; Kraemer, K. H.] NCI, Bethesda, MD 20892 USA. NR 0 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2011 VL 131 SU 1 MA 377 BP S63 EP S63 PG 1 WC Dermatology SC Dermatology GA 743RE UT WOS:000289035600377 ER PT J AU Li, S Thangapazham, RL Wang, J Rajesh, S Kao, T Sperling, L Moss, I Darling, TN AF Li, S. Thangapazham, R. L. Wang, J. Rajesh, S. Kao, T. Sperling, L. Moss, J. Darling, T. N. TI Hair follicle neogenesis induced by fibroblast-like skin tumor cells from patients with tuberous sclerosis complex SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2011 CL Phoenix, AZ SP Soc Investigat Dermatol C1 [Li, S.; Thangapazham, R. L.; Wang, J.; Rajesh, S.; Sperling, L.; Darling, T. N.] USUHS, Dept Dermatol, Bethesda, MD USA. [Moss, J.] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA. NR 0 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2011 VL 131 SU 1 MA 786 BP S131 EP S131 PG 1 WC Dermatology SC Dermatology GA 743RE UT WOS:000289035600783 ER PT J AU Martires, KI Baird, K Steinberg, SM Grkovic, L Williams, K Hakim, F Pavletic, SZ Cowen, EW AF Martires, K. I. Baird, K. Steinberg, S. M. Grkovic, L. Williams, K. Hakim, F. Pavletic, S. Z. Cowen, E. W. TI Clinical and laboratory markers of sclerotic-type chronic graft versus host disease SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2011 CL Phoenix, AZ SP Soc Investigat Dermatol C1 [Martires, K. I.; Baird, K.; Steinberg, S. M.; Grkovic, L.; Williams, K.; Hakim, F.; Pavletic, S. Z.; Cowen, E. W.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2011 VL 131 SU 1 MA 017 BP S3 EP S3 PG 1 WC Dermatology SC Dermatology GA 743RE UT WOS:000289035600016 ER PT J AU Masaki, T DiGiovanna, JJ Wang, Y Khan, SG Hornyak, T Raffeld, M Lee, C Kraemer, KH AF Masaki, T. DiGiovanna, J. J. Wang, Y. Khan, S. G. Hornyak, T. Raffeld, M. Lee, C. Kraemer, K. H. TI Genetic analysis of pre-malignant pigmented lesions in xeroderma pigmentosum patients SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2011 CL Phoenix, AZ SP Soc Investigat Dermatol C1 [Raffeld, M.; Lee, C.] NCI, Pathol Lab, Bethesda, MD 20892 USA. NR 0 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2011 VL 131 SU 1 MA 740 BP S124 EP S124 PG 1 WC Dermatology SC Dermatology GA 743RE UT WOS:000289035600738 ER PT J AU Miyagawa, F Zhang, H Ozato, K Tagaya, Y Katz, S AF Miyagawa, F. Zhang, H. Ozato, K. Tagaya, Y. Katz, S. TI IRF8 is an essential regulator of CD8 T cell effector function SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2011 CL Phoenix, AZ SP Soc Investigat Dermatol C1 [Miyagawa, F.; Zhang, H.; Tagaya, Y.; Katz, S.] NCI, Bethesda, MD 20892 USA. [Ozato, K.] NICHD, Bethesda, MD USA. NR 0 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2011 VL 131 SU 1 MA 579 BP S97 EP S97 PG 1 WC Dermatology SC Dermatology GA 743RE UT WOS:000289035600578 ER PT J AU Nelson, E Miyagawa, F Young, HA Reynolds, D Linton, J Gutermuth, J Katz, SI AF Nelson, E. Miyagawa, F. Young, H. A. Reynolds, D. Linton, J. Gutermuth, J. Katz, S. I. TI A mouse model of the cytokine storm: inhibiting IFN-gamma or TNF-alpha blocks a lethal response SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2011 CL Phoenix, AZ SP Soc Investigat Dermatol C1 [Nelson, E.; Miyagawa, F.; Young, H. A.; Reynolds, D.; Linton, J.; Gutermuth, J.; Katz, S. I.] NCI, Bethesda, MD 20892 USA. NR 0 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2011 VL 131 SU 1 MA 036 BP S6 EP S6 PG 1 WC Dermatology SC Dermatology GA 743RE UT WOS:000289035600037 ER PT J AU Schmuth, M Elentner, A Gonzalez, F Dubrac, S AF Schmuth, M. Elentner, A. Gonzalez, F. Dubrac, S. TI Pregnane X Receptor (PXR) regulates cutaneous immunity SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2011 CL Phoenix, AZ SP Soc Investigat Dermatol C1 [Schmuth, M.; Elentner, A.; Dubrac, S.] Innsbruck Med Sch, Innsbruck, Austria. [Gonzalez, F.] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. NR 0 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2011 VL 131 SU 1 MA 586 BP S98 EP S98 PG 1 WC Dermatology SC Dermatology GA 743RE UT WOS:000289035600585 ER PT J AU Silverberg, MJ Leyden, W Warton, E Engles, EA Asgari, MM AF Silverberg, M. J. Leyden, W. Warton, E. Engles, E. A. Asgari, M. M. TI HIV infection and non-melanoma skin cancer risk SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2011 CL Phoenix, AZ SP Soc Investigat Dermatol C1 [Silverberg, M. J.; Leyden, W.; Warton, E.; Asgari, M. M.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Engles, E. A.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. RI Asgari, Maryam/O-4947-2016 NR 0 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2011 VL 131 SU 1 MA 554 BP S93 EP S93 PG 1 WC Dermatology SC Dermatology GA 743RE UT WOS:000289035600553 ER PT J AU Takahashi, H Kanno, Y Nakayamada, S Kuchen-Brandes, S Casellas, R O'Shea, JJ AF Takahashi, H. Kanno, Y. Nakayamada, S. Kuchen-Brandes, S. Casellas, R. O'Shea, J. J. TI Preferential expression of miR-10a in regulatory T cells SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2011 CL Phoenix, AZ SP Soc Investigat Dermatol C1 [Takahashi, H.; Kanno, Y.; Nakayamada, S.; Kuchen-Brandes, S.; Casellas, R.; O'Shea, J. J.] NIAMSD, NIH, Bethesda, MD 20892 USA. NR 0 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2011 VL 131 SU 1 MA 556 BP S93 EP S93 PG 1 WC Dermatology SC Dermatology GA 743RE UT WOS:000289035600555 ER PT J AU Wright, LN Riss, Y Ryscavage, A Yuspa, SH AF Wright, L. N. Riss, Y. Ryscavage, A. Yuspa, S. H. TI Modeling the consequences of EGFR ablation therapy in squamous cancer by gene expression profiling of oncogenically transformed mouse keratinocytes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2011 CL Phoenix, AZ SP Soc Investigat Dermatol C1 [Wright, L. N.; Riss, Y.; Ryscavage, A.; Yuspa, S. H.] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. NR 0 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2011 VL 131 SU 1 MA 134 BP S23 EP S23 PG 1 WC Dermatology SC Dermatology GA 743RE UT WOS:000289035600136 ER PT J AU Zhou, X Khan, SG Tamura, D Compe, E Egly, J Ueda, T Boyle, J DiGiovanna, J Kraemer, KH AF Zhou, X. Khan, S. G. Tamura, D. Compe, E. Egly, J. Ueda, T. Boyle, J. DiGiovanna, J. Kraemer, K. H. TI XPD mutations in trichothiodystrophy fibroblasts inhibit TFIIH-dependent transactivation mediated by the vitamin D receptor SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2011 CL Phoenix, AZ SP Soc Investigat Dermatol C1 [Zhou, X.; Khan, S. G.; Tamura, D.; Ueda, T.; Boyle, J.; DiGiovanna, J.; Kraemer, K. H.] NCI, Bethesda, MD 20892 USA. [Zhou, X.] NIH, CRTP, Bethesda, MD 20892 USA. [Compe, E.; Ueda, T.] Inst Genet & Biol Mol & Cellulaire, Strasbourg, France. RI Compe, Emmanuel/N-8718-2016 NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2011 VL 131 SU 1 MA 378 BP S63 EP S63 PG 1 WC Dermatology SC Dermatology GA 743RE UT WOS:000289035600378 ER PT J AU Nelson, KB Chang, T Ghadini, A AF Nelson, Karin B. Chang, Taeun Ghadini, Alessandro TI Comment and reply on: Neonatal asphyxia and forensic medicine SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Letter C1 [Nelson, Karin B.] NINDS, NIH, Bethesda, MD 20892 USA. [Nelson, Karin B.; Chang, Taeun] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. [Ghadini, Alessandro] Inova Alexandria Hosp, Perinatal Diagnost Ctr, Alexandria, VA USA. RP Nelson, KB (reprint author), NINDS, NIH, 9000 Rockville Pike,Bldg 31,Room 8A03, Bethesda, MD 20892 USA. EM nelsonk@ninds.nih.gov NR 3 TC 0 Z9 0 U1 1 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PD APR PY 2011 VL 24 IS 4 BP 652 EP 652 DI 10.3109/14767051003731660 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 730GI UT WOS:000288021400021 PM 20459343 ER PT J AU Newman, JD AF Newman, John D. TI The Evolution of Language SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Book Review C1 [Newman, John D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Poolesville, MD USA. RP Newman, JD (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Poolesville, MD USA. NR 11 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 EI 1539-736X J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD APR PY 2011 VL 199 IS 4 BP 286 EP 286 DI 10.1097/NMD.0b013e31821246f0 PG 1 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 742ZX UT WOS:000288985400015 ER PT J AU Avdoshina, V Garzino-Demo, A Bachis, A Monaco, M Liu, C Young, M Mocchetti, I AF Avdoshina, V. Garzino-Demo, A. Bachis, A. Monaco, Mc Liu, C. Young, Ma Mocchetti, I. TI HIV-1 and Drugs of Abuse alter Neurotrophin Levels in Human Lymphocytes SO JOURNAL OF NEUROIMMUNE PHARMACOLOGY LA English DT Meeting Abstract C1 [Avdoshina, V.; Bachis, A.; Mocchetti, I.] Georgetown Univ, Med Ctr, Dept Neurosci, Washington, DC 20057 USA. [Garzino-Demo, A.] Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA. [Monaco, Mc] NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20824 USA. [Liu, C.; Young, Ma] Georgetown Univ, Med Ctr, Dept Med, Washington, DC 20057 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1557-1890 J9 J NEUROIMMUNE PHARM JI J. Neuroimmune Pharm. PD APR PY 2011 VL 6 SU 1 BP S24 EP S24 PG 1 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 920KF UT WOS:000302402500042 ER PT J AU Manuel, SL Makedonas, G Betts, MR Gardner, J Goedert, JJ Khan, ZK Wigdahl, B Jain, P AF Manuel, S. L. Makedonas, G. Betts, M. R. Gardner, J. Goedert, J. J. Khan, Z. K. Wigdahl, B. Jain, P. TI Dynamics of Dendritic Cells and T Cells in HTLV-1-Associated Neuroinflammatory Disease: Implications in Immunomodulatory Therapies and Diagnostic Tools SO JOURNAL OF NEUROIMMUNE PHARMACOLOGY LA English DT Meeting Abstract C1 [Manuel, S. L.; Khan, Z. K.; Jain, P.] Drexel Univ, Coll Med, Drexel Inst Biotechnol & Virol Res, Doylestown, PA 18902 USA. [Makedonas, G.; Betts, M. R.; Gardner, J.] Univ Penn, Sch Med, Dept Microbiol & Immunol, Philadelphia, PA 19104 USA. [Goedert, J. J.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Wigdahl, B.] Drexel Univ, Coll Med, Inst Mol Med & Infect Dis, Philadelphia, PA 19102 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1557-1890 J9 J NEUROIMMUNE PHARM JI J. Neuroimmune Pharm. PD APR PY 2011 VL 6 SU 1 BP S36 EP S36 PG 1 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 920KF UT WOS:000302402500077 ER PT J AU Manuel, SL Makedonas, G Betts, MR Gardner, J Goedert, JJ Khan, ZK Wigdahl, B Jain, P AF Manuel, S. L. Makedonas, G. Betts, M. R. Gardner, J. Goedert, J. J. Khan, Z. K. Wigdahl, B. Jain, P. TI Dynamics of Dendritic Cells and T Cells In HTLV-1-Associated Neuroinflammatory Disease: Implications in Immunomodulatory Therapies and Diagnostic Tools SO JOURNAL OF NEUROIMMUNE PHARMACOLOGY LA English DT Meeting Abstract C1 [Manuel, S. L.; Khan, Z. K.; Jain, P.] Drexel Univ, Coll Med, Drexel Inst Biotechnol & Virol Res, Doylestown, PA 18902 USA. [Makedonas, G.; Betts, M. R.; Gardner, J.] Univ Penn, Sch Med, Dept Microbiol & Immunol, Philadelphia, PA 19104 USA. [Goedert, J. J.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Wigdahl, B.] Drexel Univ, Coll Med, Inst Mol Med & Infect Dis, Philadelphia, PA 19102 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1557-1890 J9 J NEUROIMMUNE PHARM JI J. Neuroimmune Pharm. PD APR PY 2011 VL 6 SU 1 BP S17 EP S17 PG 1 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 920KF UT WOS:000302402500021 ER PT J AU Su, T AF Su, T. TI Molecular Chaperone and Interorganelle Signaling in Disease SO JOURNAL OF NEUROIMMUNE PHARMACOLOGY LA English DT Meeting Abstract C1 [Su, T.] Natl Inst Drug Abuse, Cellular Pathobiol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1557-1890 J9 J NEUROIMMUNE PHARM JI J. Neuroimmune Pharm. PD APR PY 2011 VL 6 SU 1 BP S20 EP S20 PG 1 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 920KF UT WOS:000302402500030 ER PT J AU Pedone, C Napoli, N Pozzilli, P Rossi, FF Lauretani, F Bandinelli, S Ferrucci, L Antonelli-Incalzi, R AF Pedone, Claudio Napoli, Nicola Pozzilli, Paolo Rossi, Francesca Flavia Lauretani, Fulvio Bandinelli, Stefania Ferrucci, Luigi Antonelli-Incalzi, Raffaele TI Dietary Pattern and Bone Density Changes in Elderly Women: A Longitudinal Study SO JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION LA English DT Article AB Objective: Few data are available on the effect of the diet in general on bone health. The objective of this study was to identify dietary patterns and to evaluate the association between such patterns and bone mineral density (BMD) changes over time. Methods: We analyzed a sample of women aged >= 65 years participating in the InCHIANTI Study. BMD was evaluated using computed tomography of the tibia and nutritional intake using the EPIC questionnaire. We used a cluster analysis to identify patterns of dietary intake. The clusters were compared with respect to nutritional intake; risk factors for osteoporosis; comorbidity; total, trabecular, and cortical BMD; and BMD changes over 6 years. Results: The sample size was 434, with a mean age of 75.2 years (SD, 7.01 years; range, 65-94 years). Based on dietary variables, 2 clusters were identified with a marked difference in energy intake (30 kcal/kg of ideal body weight [IBW] in cluster 1 vs 44 kcal/kg IBW in cluster 2). We found no meaningful differences between clusters with regard to nondietary risk factors for osteoporosis, BMD measured at baseline, and changes in BMD over the 6-year follow-up; cluster 2 showed a greater increase in cortical BMD (+30.2 mg/cm(3) vs +16.7 mg/cm(3)). Members of cluster 2 were less likely to have a lower cortical BMD increase (adjusted odds ratio, 0.452; 95% confidence interval, 0.215-0.950). Conclusions: Cortical BMD increases more in participants eating a diet exceeding the RDA for macronutrients. Cortical BMD may be more sensitive to diet and dietary interventions than trabecular bone. C1 [Pedone, Claudio; Rossi, Francesca Flavia; Antonelli-Incalzi, Raffaele] Univ Campus Biomed, Area Geriatria, I-00128 Rome, Italy. [Pedone, Claudio; Napoli, Nicola; Pozzilli, Paolo] Fdn Alberto Sordi ONLUS, Rome, Italy. [Napoli, Nicola; Pozzilli, Paolo] Univ Campus Biomed, Area Endocrinol & Malattie Metab, I-00128 Rome, Italy. [Lauretani, Fulvio] Tuscany Reg Hlth Agcy, Florence, Italy. [Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Rehabil Unit, Florence, Italy. [Antonelli-Incalzi, Raffaele] Fdn San Raffaele Cittadella Carita, Taranto, Italy. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA. RP Pedone, C (reprint author), Univ Campus Biomed, Area Geriatria, Via Alvaro del Portillo 21, I-00128 Rome, Italy. EM c.pedone@unicampus.it RI Antonelli Incalzi, Raffaele/G-3978-2012; Lauretani, Fulvio/K-5115-2016 OI Napoli, Nicola/0000-0002-3091-8205; Pedone, Claudio/0000-0003-1847-9032; Antonelli Incalzi, Raffaele/0000-0003-2100-2075; Lauretani, Fulvio/0000-0002-5287-9972 NR 25 TC 8 Z9 10 U1 1 U2 4 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0731-5724 J9 J AM COLL NUTR JI J. Am. Coll. Nutr. PD APR PY 2011 VL 30 IS 2 BP 149 EP 154 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA V28MP UT WOS:000208685200008 PM 21730223 ER PT J AU Clemens, K Larsen, L Zhang, M Kuznetsov, Y Bilanchone, V Randall, A Harned, A DaSilva, R Nagashima, K McPherson, A Baldi, P Sandmeyer, S AF Clemens, Kristina Larsen, Liza Zhang, Min Kuznetsov, Yurii Bilanchone, Virginia Randall, Arlo Harned, Adam DaSilva, Rhonda Nagashima, Kunio McPherson, Alexander Baldi, Pierre Sandmeyer, Suzanne TI The TY3 Gag3 Spacer Controls Intracellular Condensation and Uncoating SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ROUS-SARCOMA-VIRUS; PFIZER MONKEY VIRUS; TYPE-1 GAG; REVERSE TRANSCRIPTION; RETROVIRAL PROTEASE; MEMBRANE-BINDING; P2(GAG) PEPTIDE; CLEAVAGE SITES; CAPSID PROTEIN AB Cells expressing the yeast retrotransposon Ty3 form concentrated foci of Ty3 proteins and RNA within which virus-like particle (VLP) assembly occurs. Gag3, the major structural protein of the Ty3 retrotransposon, is composed of capsid (CA), spacer (SP), and nucleocapsid (NC) domains analogous to retroviral domains. Unlike the known SP domains of retroviruses, Ty3 SP is highly acidic. The current studies investigated the role of this domain. Although deletion of Ty3 SP dramatically reduced retrotransposition, significant Gag3 processing and cDNA synthesis occurred. Mutations that interfered with cleavage at the SP-NC junction disrupted CA-SP processing, cDNA synthesis, and electron-dense core formation. Mutations that interfered with cleavage of CA-SP allowed cleavage of the SP-NC junction, production of electron-dense cores, and cDNA synthesis but blocked retrotransposition. A mutant in which acidic residues of SP were replaced with alanine failed to form both Gag3 foci and VLPs. We propose a speculative "spring" model for Gag3 during assembly. In the first phase during concentration of Gag3 into foci, intramolecular interactions between negatively charged SP and positively charged NC domains of Gag3 limit multimerization. In the second phase, the NC domain binds RNA, and the bound form is stabilized by intermolecular interactions with the SP domain. These interactions promote CA domain multimerization. In the third phase, a negatively charged SP domain destabilizes the remaining CA-SP shell for cDNA release. C1 [Clemens, Kristina; Zhang, Min; Bilanchone, Virginia; Sandmeyer, Suzanne] Univ Calif Irvine, Dept Biol Chem, Irvine, CA 92697 USA. [Larsen, Liza; McPherson, Alexander; Sandmeyer, Suzanne] Univ Calif Irvine, Dept Microbiol & Mol Genet, Irvine, CA 92697 USA. [Kuznetsov, Yurii; Baldi, Pierre; Sandmeyer, Suzanne] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA. [Randall, Arlo; Baldi, Pierre; Sandmeyer, Suzanne] Univ Calif Irvine, Dept Comp Sci, Irvine, CA 92697 USA. [Randall, Arlo] Univ Calif Irvine, Inst Genom & Bioinformat, Irvine, CA 92697 USA. [Harned, Adam; DaSilva, Rhonda; Nagashima, Kunio] SAIC Frederick Inc, NCI Frederick, Electron Microscope Lab, Frederick, MD 21702 USA. RP Sandmeyer, S (reprint author), Univ Calif Irvine, Dept Biol Chem, Irvine, CA 92697 USA. EM sbsandme@uci.edu RI zhang, min/C-6300-2011 FU National Institutes of Health (NIH), Public Health Service [GM33281]; NSF [EF-0330786]; NIH [CA112560, LM-07443-01, GM58868]; NCI, NIH [HHSN26120080001E] FX This research was supported in whole or in part by funds from the National Institutes of Health (NIH), Public Health Service grant GM33281 to S. S., NSF EF-0330786, NIH CA112560, and NIH LM-07443-01 to P. B., GM58868 to A. M., and NCI, NIH, contract HHSN26120080001E to K.N. NR 47 TC 6 Z9 6 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2011 VL 85 IS 7 BP 3055 EP 3066 DI 10.1128/JVI.01055-10 PG 12 WC Virology SC Virology GA 734WT UT WOS:000288373000002 PM 21270167 ER PT J AU McDonald, SM Patton, JT AF McDonald, Sarah M. Patton, John T. TI Rotavirus VP2 Core Shell Regions Critical for Viral Polymerase Activation SO JOURNAL OF VIROLOGY LA English DT Article ID NONSTRUCTURAL PROTEIN NSP5; STRANDED-RNA GENOME; REPLICATION; PARTICLES; RESOLUTION; MECHANISM AB The innermost VP2 core shell of the triple-layered, icosahedral rotavirus particle surrounds the viral genome and RNA processing enzymes, including the RNA-dependent RNA polymerase (VP1). In addition to anchoring VP1 within the core, VP2 is also an essential cofactor that triggers the polymerase to initiate double-stranded RNA (dsRNA) synthesis using packaged plus-strand RNA templates. The VP2 requirement effectively couples packaging with genome replication and ensures that VP1 makes dsRNA only within an assembling previrion particle. However, the mechanism by which the rotavirus core shell protein activates the viral polymerase remains very poorly understood. In the current study, we sought to elucidate VP2 regions critical for VP1-mediated in vitro dsRNA synthesis. By comparing the functions of proteins from several different rotaviruses, we found that polymerase activation by the core shell protein is specific. Through truncation and chimera mutagenesis, we demonstrate that the VP2 amino terminus, which forms a decameric, internal hub underneath each 5-fold axis, plays an important but nonspecific role in VP1 activation. Our results indicate that the VP2 residues correlating with polymerase activation specificity are located on the inner face of the core shell, distinct from the amino terminus. Based on these findings, we predict that several regions of VP2 engage the polymerase during the concerted processes of rotavirus core assembly and genome replication. C1 [McDonald, Sarah M.; Patton, John T.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP McDonald, SM (reprint author), NIAID, Infect Dis Lab, NIH, 50 South Dr,Room 6311, Bethesda, MD 20892 USA. EM mcdonaldsa@niaid.nih.gov RI Patton, John/P-1390-2014 FU National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This study was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 27 TC 22 Z9 22 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2011 VL 85 IS 7 BP 3095 EP 3105 DI 10.1128/JVI.02360-10 PG 11 WC Virology SC Virology GA 734WT UT WOS:000288373000006 PM 21248043 ER PT J AU Sakakibara, S Sakakibara, K Tosato, G AF Sakakibara, Shuhei Sakakibara, Kaori Tosato, Giovanna TI NF-kappa B Activation Stimulates Transcription and Replication of Retrovirus XMRV in Human B-Lineage and Prostate Carcinoma Cells SO JOURNAL OF VIROLOGY LA English DT Article ID VIRUS-RELATED VIRUS; CHRONIC-FATIGUE-SYNDROME; TUMOR-NECROSIS-FACTOR; INFECTIOUS RETROVIRUS; CANCER; RECEPTOR; BLOOD; CARCINOGENESIS; INFLAMMATION; PREVALENCE AB Xenotropic murine leukemia virus-related virus (XMRV) is a gammaretrovirus linked to prostate carcinoma and chronic fatigue syndrome. Here we report that NF-kappa B activation can markedly increase XMRV production. The inflammatory cytokine tumor necrosis factor alpha (TNF-alpha), which activates NF-kappa B, significantly augmented viral Gag protein production in XMRV-infected cells. Reporter assays showed that TNF-alpha and Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1), an intrinsic NF-kappa B activator, increased long terminal repeat (LTR)-dependent XMRV transcription. We identified two NF-kappa B binding sites (designated kappa B-1 and kappa B-2) in the LTR U3 region of XMRV and demonstrated that both sites bind to the NF-kappa B component p65/RelA. Mutation of the kappa B-1 site, but not the kappa B-2 site, impaired responsiveness to TNF-alpha and LMP1 in reporter assays. A mutant XMRV with a mutation at the kappa B-1 site replicated significantly less efficiently than the wild-type XMRV in the prostate carcinoma LNCaP, DU145, and PC-3 cell lines, HEK293 cells, the EBV-immortalized cell line IB4, and the Burkitt's lymphoma cell line BJAB. These results demonstrate that TNF-alpha and EBV LMP1 enhance XMRV replication in prostate carcinoma and B-lineage cells through the kappa B-1 site in the XMRV LTR, suggesting that inflammation, EBV infection, and other conditions leading to NF-kappa B activation may promote XMRV spread in humans. C1 [Sakakibara, Shuhei; Tosato, Giovanna] NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Sakakibara, Kaori] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Sakakibara, S (reprint author), NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bldg 37,Room 4134, Bethesda, MD 20892 USA. EM sakakibs@mail.nih.gov FU Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health, Bethesda, MD FX This study was supported by the intramural research program of the Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health, Bethesda, MD. NR 39 TC 9 Z9 9 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2011 VL 85 IS 7 BP 3179 EP 3186 DI 10.1128/JVI.02333-10 PG 8 WC Virology SC Virology GA 734WT UT WOS:000288373000014 PM 21270144 ER PT J AU Kawaguchi, K Faulk, K Purcell, RH Emerson, SU AF Kawaguchi, Kazunori Faulk, Kristina Purcell, Robert H. Emerson, Suzanne U. TI Reproduction In Vitro of a Quasispecies from a Hepatitis C Virus-Infected Patient and Determination of Factors That Influence Selection of a Dominant Species SO JOURNAL OF VIROLOGY LA English DT Article ID HYPERVARIABLE REGION 1; B TYPE-I; HYPERIMMUNE SERUM; ENVELOPE PROTEIN; CULTURE; CHIMPANZEES; MUTATIONS; RECEPTOR AB Hepatitis C virus infections proceed to chronicity in the majority of cases. In patients, hepatitis C viruses exist as a dynamic and complex quasispecies. The dominant species at any one time arises in response to host immune pressure and other, incompletely understood factors. It is critical to understand all the mechanisms by which dominance is achieved, but this is difficult to study in vivo. Therefore, it would be useful to develop a cell culture system in which naturally occurring quasispecies could be studied. Hepatitis C virus glycoprotein genes E1 and E2 were PCR amplified as a cassette from the plasma of a chronically infected patient and shotgun cloned into a modified 1a/JFH1 infectious cDNA clone. Following transformation of bacteria, plasmids were batch harvested, transcribed, and transfected into Huh7.5 cells to produce a quasispecies of hypervariable region 1 (HVR1) that mimicked that circulating in vivo. Serial passage of the quasispecies in vitro resulted in replacement of the initially dominant species with a new HVR1 species coexisting with selected growth-enhancing mutations located outside HVR1. Antibody raised against one HVR1 sequence neutralized virus with the homologous HVR1 and cross-neutralized virus with a different sequence. Reciprocal swapping of the HVR1 regions between the two dominating species demonstrated that the HVR1 sequence affects the efficiency of replication and of neutralization by anti-HVR1 but that both processes are strongly influenced by regions outside HVR1. C1 [Emerson, Suzanne U.] NIAID, Mol Hepatitis Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Emerson, SU (reprint author), NIAID, Mol Hepatitis Sect, Infect Dis Lab, NIH, Bldg 50,Room 6537, Bethesda, MD 20892 USA. EM semerson@niaid.nih.gov FU NIH, Institute of Allergy and Infectious Diseases FX This research was supported by the Intramural Research Program of NIH, Institute of Allergy and Infectious Diseases. NR 21 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2011 VL 85 IS 7 BP 3408 EP 3414 DI 10.1128/JVI.02554-10 PG 7 WC Virology SC Virology GA 734WT UT WOS:000288373000034 PM 21270157 ER PT J AU Xu, WQ Eiden, MV AF Xu, Wenqin Eiden, Maribeth V. TI Primate Gammaretroviruses Require an Ancillary Factor Not Required for Murine Gammaretroviruses To Infect BHK Cells SO JOURNAL OF VIROLOGY LA English DT Article ID APE LEUKEMIA-VIRUS; TRANSMEMBRANE PROTEINS; SURFACE RECEPTOR; RETROVIRUS; HETEROKARYONS; TOPOLOGY; GENE; IDENTIFICATION; PROTEOGLYCANS; TRANSDUCTION AB BHK cells remain resistant to xenotropic murine retrovirus-related virus (XMRV) or gibbon ape leukemia virus (GALV) infection, even when their respective receptors, Xpr1 or PiT1, are expressed. We set out to determine the stage at which viral infection is blocked and whether this block is mediated by a dominant-negative factor or the absence of a requisite ancillary factor. BHK cells bind neither XMRV nor GALV envelope proteins. BHK cells expressing the appropriate receptors bind XMRV or GALV envelope proteins. BHK cells can be infected by NZB-XMV(New Zealand Black mouse xenotropic murine virus)-enveloped vectors, expressing an envelope derived from a xenotropic retrovirus that, like XMRV, employs Xpr1 as a receptor, and also by vectors bearing the envelope of 10A1 murine leukemia virus (MLV), a murine retrovirus that can use PiT1 as a receptor. The retroviral vectors used in these analyses differ solely in their viral envelope proteins, suggesting that the block to XMRV and GALV infection is mediated at the level of envelope-receptor interactions. N-linked glycosylation of the receptors was not found to mediate resistance of receptor-expressing BHK cells to GALV or XMRV, as shown by tunicamycin treatment and mutation of the specific glycosylation site of the PiT1 receptor. Hybrid cells produced by fusing BHKXpr1 or BHKPiT1 to XMRV- or GALV-resistant cells, respectively, can mediate efficient XMRV or GALV infection. These findings indicate that BHK cells lack a factor that is required for infection by primate xenotropic viruses. This factor is not required for viruses that use the same receptors but were directly isolated from mice. C1 [Xu, Wenqin; Eiden, Maribeth V.] NIMH, Sect Mol Virol, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. RP Eiden, MV (reprint author), NIMH, Sect Mol Virol, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. EM eidenm@mail.nih.gov NR 36 TC 6 Z9 6 U1 0 U2 24 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2011 VL 85 IS 7 BP 3498 EP 3506 DI 10.1128/JVI.02586-10 PG 9 WC Virology SC Virology GA 734WT UT WOS:000288373000042 PM 21270153 ER PT J AU Burwitz, BJ Ende, Z Sudolcan, B Reynolds, MR Greene, JM Bimber, BN Almeida, JR Kurniawan, M Venturi, V Gostick, E Wiseman, RW Douek, DC Price, DA O'Connor, DH AF Burwitz, Benjamin J. Ende, Zachary Sudolcan, Benjamin Reynolds, Matthew R. Greene, Justin M. Bimber, Benjamin N. Almeida, Jorge R. Kurniawan, Monica Venturi, Vanessa Gostick, Emma Wiseman, Roger W. Douek, Daniel C. Price, David A. O'Connor, David H. TI Simian Immunodeficiency Virus SIVmac239 Delta nef Vaccination Elicits Different Tat(28-35)SL8-Specific CD8(+) T-Cell Clonotypes Compared to a DNA Prime/Adenovirus Type 5 Boost Regimen in Rhesus Macaques SO JOURNAL OF VIROLOGY LA English DT Article ID SIV INFECTION; CHALLENGE; RESPONSES; LIVE; REPLICATION; ESCAPE; REPERTOIRE; PROTECTION; SIVMAC239; DEPLETION AB Different human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) vaccine vectors expressing the same viral antigens can elicit disparate T-cell responses. Within this spectrum, replicating variable vaccines, like SIVmac239 Delta nef, appear to generate particularly efficacious CD8(+) T-cell responses. Here, we sequenced T-cell receptor beta-chain (TRB) gene rearrangements from immunodominant Mamu-A*01-restricted Tat(28-35)SL8-specific CD8(+) T-cell populations together with the corresponding viral epitope in four rhesus macaques during acute SIVmac239 Delta nef infection. Ultradeep pyrosequencing showed that viral variants arose with identical kinetics in SIVmac239 Delta nef and pathogenic SIVmac239 infection. Furthermore, distinct Tat(28-35)SL8-specific T-cell receptor (TCR) repertoires were elicited by SIVmac239 Delta nef compared to those observed following a DNA/Ad5 prime-boost regimen, likely reflecting differences in antigen sequence stability. C1 [Burwitz, Benjamin J.; Reynolds, Matthew R.; Greene, Justin M.; O'Connor, David H.] Univ Wisconsin, Dept Pathol, Madison, WI 53706 USA. [Ende, Zachary; Almeida, Jorge R.; Douek, Daniel C.; Price, David A.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Sudolcan, Benjamin; Bimber, Benjamin N.; Wiseman, Roger W.; O'Connor, David H.] Wisconsin Natl Primate Res Ctr, Madison, WI 53706 USA. [Kurniawan, Monica; Venturi, Vanessa] Univ New S Wales, Computat Biol Unit, Ctr Vasc Res, Kensington, NSW 2052, Australia. [Gostick, Emma; Price, David A.] Cardiff Univ, Sch Med, Dept Infect Immun & Biochem, Cardiff CF14 4XN, S Glam, Wales. RP O'Connor, DH (reprint author), Univ Wisconsin, Dept Pathol, 555 Sci Dr, Madison, WI 53711 USA. EM doconnor@primate.wisc.edu RI Price, David/C-7876-2013; OI Price, David/0000-0001-9416-2737; Ramos de Almeida, Jorge/0000-0002-5009-8478 FU National Center for Research Resources (NCRR) [P51 RR000167]; National Institutes of Health (NIH); Research Facilities Improvement Program [RR15459-01, RR020141-01]; NIH [1R01AI084787, R01 AI077376, 144PRJ23CG] FX This publication was made possible by grant number P51 RR000167 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), to the Wisconsin National Primate Research Center, University of Wisconsin-Madison; the research was conducted at a facility constructed with support from the Research Facilities Improvement Program, grant numbers RR15459-01 and RR020141-01. Additional funding was provided by grant numbers 1R01AI084787, R01 AI077376, and 144PRJ23CG from the NIH. D.A.P. is a Medical Research Council (United Kingdom) Senior Clinical Fellow; V.V. is an Australian Research Council Future Fellow. NR 22 TC 9 Z9 9 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2011 VL 85 IS 7 BP 3683 EP 3689 DI 10.1128/JVI.02112-10 PG 7 WC Virology SC Virology GA 734WT UT WOS:000288373000059 PM 21270159 ER PT J AU Inlora, J Chukkapalli, V Derse, D Ono, A AF Inlora, Jingga Chukkapalli, Vineela Derse, David Ono, Akira TI Gag Localization and Virus-Like Particle Release Mediated by the Matrix Domain of Human T-Lymphotropic Virus Type 1 Gag Are Less Dependent on Phosphatidylinositol-(4,5)-Bisphosphate than Those Mediated by the Matrix Domain of HIV-1 Gag SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LEUKEMIA-VIRUS; MEMBRANE-BINDING; PLASMA-MEMBRANE; MYRISTYL SWITCH; 3-DIMENSIONAL STRUCTURE; TERMINAL REGION; BASIC REGION; PROTEIN; RNA AB The human immunodeficiency virus type 1 (HIV-1) Gag matrix (MA) domain facilitates Gag targeting and binding to the plasma membrane (PM) during virus assembly. Interaction with a PM phospholipid, phosphatidylinositol-(4,5)-bisphosphate [ PI(4,5)P(2)], plays a key role in these MA functions. Previous studies showed that overexpression of polyphosphoinositide 5-phosphatase IV (5ptaseIV), which depletes cellular PI(4,5)P(2), mislocalizes HIV-1 Gag to the cytosol and greatly reduces HIV-1 release efficiency. In this study, we sought to determine the role of the MA-PI(4,5)P(2) interaction in Gag localization and membrane binding of a deltaretrovirus, human T-lymphotropic virus type 1 (HTLV-1). We compared the chimeric HIV-1 Gag (HTMA), in which MA was replaced with HTLV-1 MA, with wild-type HIV-1 and HTLV-1 Gag for PI(4,5)P(2) dependence. Our results demonstrate that, unlike HIV-1 Gag, subcellular localization of and VLP release by HTLV-1 and HTMA Gag were minimally sensitive to 5ptaseIV overexpression. These results suggest that the interaction of HTLV-1 MA with PI(4,5)P(2) is not essential for HTLV-1 particle assembly. Furthermore, liposome-binding analyses showed that both HTLV-1 and HTMA Gag can bind membrane efficiently even in the absence of PI(4,5)P(2). Efficient HTLV-1 Gag binding to liposomes was largely driven by electrostatic interaction, unlike that of HIV-1 Gag, which required specific interaction with PI(4,5)P(2). Furthermore, membrane binding of HTLV-1 Gag in vitro was not suppressed by RNA, in contrast to HIV-1 Gag. Altogether, our data suggest that Gag targeting and membrane binding mediated by HTLV-1 MA does not require PI(4,5)P(2) and that distinct mechanisms regulate HIV-1 and HTLV-1 Gag membrane binding. C1 [Inlora, Jingga; Chukkapalli, Vineela; Ono, Akira] Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA. [Derse, David] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. RP Ono, A (reprint author), Univ Michigan, Sch Med, Dept Microbiol & Immunol, 1150 W Med Ctr Dr, Ann Arbor, MI 48109 USA. EM akiraono@umich.edu OI Ono, Akira/0000-0001-7841-851X FU NIH [R01 AI071727] FX This study is supported by NIH grant R01 AI071727 to A.O. NR 73 TC 40 Z9 40 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2011 VL 85 IS 8 BP 3802 EP 3810 DI 10.1128/JVI.02383-10 PG 9 WC Virology SC Virology GA 736ZV UT WOS:000288536100010 PM 21289126 ER PT J AU Chaiwatpongsakorn, S Epand, RF Collins, PL Epand, RM Peeples, ME AF Chaiwatpongsakorn, Supranee Epand, Raquel F. Collins, Peter L. Epand, Richard M. Peeples, Mark E. TI Soluble Respiratory Syncytial Virus Fusion Protein in the Fully Cleaved, Pretriggered State Is Triggered by Exposure to Low-Molarity Buffer SO JOURNAL OF VIROLOGY LA English DT Article ID 2 DISTINCT SITES; MEMBRANE-FUSION; CELL-FUSION; F-PROTEIN; HEMAGGLUTININ-NEURAMINIDASE; HALOPHILIC PROTEINS; ELECTRON-MICROSCOPY; LIPOSOME BINDING; SENDAI-VIRUS; SUBGROUP-B AB The paramyxovirus fusion (F) glycoprotein is anchored in the virion membrane in a metastable, pretriggered form. Once triggered, the F protein undergoes a dramatic conformational extension that inserts its hydrophobic fusion peptide into the target cell membrane, then folds back on itself to bring the membranes together and initiate fusion. Unlike most other paramyxoviruses, the respiratory syncytial virus (RSV) F protein alone is sufficient to mediate membrane fusion and virus infection. To study the triggering mechanism of the RSV F protein, we have generated a soluble F (sF) protein by replacing the transmembrane and cytoplasmic tail domains with a 6His tag. The sF protein is secreted efficiently from 293T cells in a fully cleaved form. It is recognized by neutralizing monoclonal antibodies, appears spherical by electron microscopic analysis, and is not aggregated, all consistent with a native, pretriggered trimer. The sF protein was purified on a Ni(+2) column and eluted with 50 mM phosphate buffer containing 500 mM NaCl and 250 mM imidazole. Dialysis against 10 mM buffer caused the sF protein to trigger, forming "hat pin"-shaped molecules that aggregated as rosettes, characteristic of the posttriggered form. Further dialysis experiments indicated that the efficiency of triggering correlated well with the reduction of buffer molarity. Reduction of buffer molarity by dilution also resulted in exposure of the fusion peptide, as detected by liposome association, confirming sF protein triggering. Mutation of the furin cleavage site adjacent to the fusion peptide prevented liposome association, further confirming that association is via the fusion peptide. C1 [Chaiwatpongsakorn, Supranee; Peeples, Mark E.] Nationwide Childrens Hosp, Res Inst, Ctr Vaccines & Immun, Columbus, OH 43205 USA. [Peeples, Mark E.] Ohio State Univ, Coll Med, Dept Pediat, Columbus, OH 43205 USA. [Chaiwatpongsakorn, Supranee] Ohio State Univ, Coll Vet Med, Vet Biosci Grad Program, Columbus, OH 43210 USA. [Epand, Raquel F.; Epand, Richard M.] McMaster Univ, Hlth Sci Ctr, Dept Biochem & Biomed Sci, Hamilton, ON L8N 3Z5, Canada. [Collins, Peter L.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Peeples, ME (reprint author), Nationwide Childrens Hosp, Res Inst, Ctr Vaccines & Immun, 700 Childrens Dr, Columbus, OH 43205 USA. EM mark.peeples@nationwidechildrens.org FU National Institutes of Health [AI47213]; The Research Institute at Nationwide Children's Hospital; Canadian Institutes of Health Research [MOP 86608]; NIAID, NIH FX This work was supported by grant AI47213 from the National Institutes of Health and funds from The Research Institute at Nationwide Children's Hospital. R.M.E. was supported by grant MOP 86608 from the Canadian Institutes of Health Research. P.L.C. was supported by the Intramural Program of NIAID, NIH. NR 48 TC 32 Z9 34 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2011 VL 85 IS 8 BP 3968 EP 3977 DI 10.1128/JVI.01813-10 PG 10 WC Virology SC Virology GA 736ZV UT WOS:000288536100025 PM 21307202 ER PT J AU Schaap-Nutt, A Higgins, C Amaro-Carambot, E Nolan, SM D'Angelo, C Murphy, BR Collins, PL Schmidt, AC AF Schaap-Nutt, Anne Higgins, Caraline Amaro-Carambot, Emerito Nolan, Sheila M. D'Angelo, Christopher Murphy, Brian R. Collins, Peter L. Schmidt, Alexander C. TI Identification of Human Parainfluenza Virus Type 2 (HPIV-2) V Protein Amino Acid Residues That Reduce Binding of V to MDA5 and Attenuate HPIV-2 Replication in Nonhuman Primates SO JOURNAL OF VIROLOGY LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; INDUCIBLE RNA HELICASE; CYSTEINE-RICH DOMAIN; L-POLYMERASE PROTEIN; RIG-I; VACCINE CANDIDATES; INTERFERON-PRODUCTION; INNATE IMMUNITY; HETEROLOGOUS PARAMYXOVIRUSES; ALPHA/BETA-INTERFERON AB Human parainfluenza virus type 2 (HPIV-2), an important pediatric respiratory pathogen, encodes a V protein that inhibits type I interferon (IFN) induction and signaling. Using reverse genetics, we attempted the recovery of a panel of V mutant viruses that individually contained one of six cysteine-to-serine (residues 193, 197, 209, 211, 214, and 218) substitutions, one of two paired charge-to-alanine (R175A/R176A and R205A/K206A) substitutions, or a histidine-to-phenylalanine (H174F) substitution. This mutagenesis was performed using a cDNA-derived HPIV-2 virus that expressed the V and P coding sequences from separate mRNAs. Of the cysteine substitutions, only C193S, C214S, and C218S yielded viable virus, and only the C214S mutant replicated well enough for further analysis. The H174F, R175A/R176A, and R205A/K206A mutants were viable and replicated well. The H174F and R205A/K206A mutants did not differ from the wild-type (WT) V in their ability to physically interact with MDA5, a cytoplasmic sensor of nonself RNA that induces type I IFN. Like WT HPIV-2, these mutants inhibited IFN-beta induction and replicated efficiently in African green monkeys (AGMs). In contrast, the C214S and R175A/R176A mutants did not bind MDA5 efficiently, did not inhibit interferon regulatory factor 3 (IRF3) dimerization or IFN-beta induction, and were attenuated in AGMs. These findings indicate that V binding to MDA5 is important for HPIV-2 virulence in nonhuman primates and that some V protein residues involved in MDA5 binding are not essential for efficient HPIV-2 growth in vitro. Using a transient expression system, 20 additional mutant V proteins were screened for MDA5 binding, and the region spanning residues 175 to 180 was found to be essential for this activity. C1 [Schaap-Nutt, Anne; Higgins, Caraline; Amaro-Carambot, Emerito; Nolan, Sheila M.; D'Angelo, Christopher; Murphy, Brian R.; Collins, Peter L.; Schmidt, Alexander C.] NIAID, LID, NIH, RNA Viruses Sect,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Schmidt, AC (reprint author), NIAID, LID, NIH, RNA Viruses Sect,Dept Hlth & Human Serv, 50 S Dr,Room 6511,MSC 8007, Bethesda, MD 20892 USA. EM schmidta@niaid.nih.gov FU National Institute of Allergy and Infectious Disease, National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Disease, National Institutes of Health, and was performed partly under a cooperative research and development agreement (CRADA) between NIAID and MedImmune, LLC (CRADA no. AI-5114), for the development of live attenuated virus vaccines for respiratory syncytial viruses, parainfluenza viruses, and human metapneumovirus. NR 67 TC 10 Z9 10 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2011 VL 85 IS 8 BP 4007 EP 4019 DI 10.1128/JVI.02542-10 PG 13 WC Virology SC Virology GA 736ZV UT WOS:000288536100029 PM 21289116 ER PT J AU Tang, ZS Zhang, SH Lee, C Kumar, A Arjunan, P Li, Y Zhang, F Li, XR AF Tang, Zhongshu Zhang, Shuihua Lee, Chunsik Kumar, Anil Arjunan, Pachiappan Li, Yang Zhang, Fan Li, Xuri TI An Optic Nerve Crush Injury Murine Model to Study Retinal Ganglion Cell Survival SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Neuroscience; Issue 50; optic nerve crush injury; retinal ganglion cell; glaucoma; optic neuropathy; retrograde labeling AB Injury to the optic nerve can lead to axonal degeneration, followed by a gradual death of retinal ganglion cells (RGCs), which results in irreversible vision loss. Examples of such diseases in human include traumatic optic neuropathy and optic nerve degeneration in glaucoma. It is characterized by typical changes in the optic nerve head, progressive optic nerve degeneration, and loss of retinal ganglion cells, if uncontrolled, leading to vision loss and blindness. The optic nerve crush (ONC) injury mouse model is an important experimental disease model for traumatic optic neuropathy, glaucoma, etc. In this model, the crush injury to the optic nerve leads to gradual retinal ganglion cells apoptosis. This disease model can be used to study the general processes and mechanisms of neuronal death and survival, which is essential for the development of therapeutic measures. In addition, pharmacological and molecular approaches can be used in this model to identify and test potential therapeutic reagents to treat different types of optic neuropathy. Here, we provide a step by step demonstration of (I) Baseline retrograde labeling of retinal ganglion cells (RGCs) at day 1, (II) Optic nerve crush injury at day 4, (III) Harvest the retinae and analyze RGC survival at day 11, and (IV) Representative result. C1 [Tang, Zhongshu; Zhang, Shuihua; Lee, Chunsik; Kumar, Anil; Arjunan, Pachiappan; Li, Yang; Zhang, Fan; Li, Xuri] NEI, NIH, Bethesda, MD 20892 USA. [Zhang, Shuihua] Harbin Med Univ, Hosp 2, Ophthalmol Dept, Harbin, Peoples R China. RP Li, XR (reprint author), NEI, NIH, Bethesda, MD 20892 USA. EM lixur@nei.nih.gov FU NIH, National Eye Institute FX Our research is supported by the Intramural Research Program of the NIH, National Eye Institute. NR 7 TC 0 Z9 0 U1 1 U2 2 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD APR PY 2011 IS 50 AR e2685 DI 10.3791/2685 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V36LZ UT WOS:000209214700039 ER PT J AU Zheng, CY Petralia, RS Wang, YX Kachar, B AF Zheng, Chan-Ying Petralia, Ronald S. Wang, Ya-Xian Kachar, Bechara TI Fluorescence Recovery After Photobleaching (FRAP) of Fluorescence Tagged Proteins in Dendritic Spines of Cultured Hippocampal Neurons SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Neuroscience; Issue 50; Spine; FRAP; hippocampal neurons; live cell imaging; protein mobility AB FRAP has been used to quantify the mobility of GFP-tagged proteins. Using a strong excitation laser, the fluorescence of a GFP-tagged protein is bleached in the region of interest. The fluorescence of the region recovers when the unbleached GFP-tagged protein from outside of the region diffuses into the region of interest. The mobility of the protein is then analyzed by measuring the fluorescence recovery rate. This technique could be used to characterize protein mobility and turnover rate. In this study, we express the (enhanced green fluorescent protein) EGFP vector in cultured hippocampal neurons. Using the Zeiss 710 confocal microscope, we photobleach the fluorescence signal of the GFP protein in a single spine, and then take time lapse images to record the fluorescence recovery after photobleaching. Finally, we estimate the percentage of mobile and immobile fractions of the GFP in spines, by analyzing the imaging data using Image J and Graphpad softwares. This FRAP protocol shows how to perform a basic FRAP experiment as well as how to analyze the data. C1 [Zheng, Chan-Ying; Petralia, Ronald S.; Wang, Ya-Xian; Kachar, Bechara] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD 20892 USA. RP Zheng, CY (reprint author), Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD 20892 USA. EM zhengchan@mail.nih.gov FU National Institute on Deafness and Other Communication Disorders (NIDCD) Intramural Program FX This work was supported by the National Institute on Deafness and Other Communication Disorders (NIDCD) Intramural Program. NR 6 TC 1 Z9 1 U1 0 U2 1 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD APR PY 2011 IS 50 AR e2568 DI 10.3791/2568 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V36LZ UT WOS:000209214700014 ER PT J AU Nayeem, MA Zeldin, DC Boegehold, MA Falck, JR AF Nayeem, Mohammed A. Zeldin, Darryl C. Boegehold, Matthew A. Falck, John R. TI Salt modulates vascular response through adenosine A(2A) receptor in eNOS-null mice: role of CYP450 epoxygenase and soluble epoxide hydrolase SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE Salt; eNOS; CYP2J2; sEH; Relaxation; Adenosine ID NITRIC-OXIDE SYNTHASE; CORONARY ARTERIOLAR DILATION; HYPERPOLARIZING FACTOR; EPOXYEICOSATRIENOIC ACIDS; KNOCKOUT MICE; SKELETAL-MUSCLE; 11,12-EPOXYEICOSATRIENOIC ACID; PULMONARY-HYPERTENSION; INDUCED VASODILATION; EXERCISE HYPEREMIA AB High salt (HS) intake can change the arterial tone in mice, and the nitric oxide (NO) acts as a mediator to some of the receptors mediated vascular response. The main aim of this study was to explore the mechanism behind adenosine-induced vascular response in HS-fed eNOS(+/+) and eNOS(-/-) mice The modulation of vascular response by HS was examined using aortas from mice (eNOS(+/+) and eNOS(-/-)) fed 4% (HS) or 0.45% (NS) NaCl-diet through acetylcholine (ACh), NECA (adenosine-analog), CGS 21680 (A(2A) AR-agonist), MS-PPOH (CYP epoxygenase-blocker; 10(-5) M), AUDA (sEH-blocker; 10(-5) M), and DDMS (CYP4A-blocker; 10(-5) M). ACh-response was greater in HS-eNOS(+/+) (+59.3 +/- A 6.3%) versus NS-eNOS(+/+) (+33.3 +/- A 8.0%; P < 0.05). However, there was no response in both HS-eNOS(-/-) and NS-eNOS(-/-). NECA-response was greater in HS-eNOS(-/-) (+37.4 +/- A 3.2%) versus NS-eNOS(-/-) (+7.4.0 +/- A 3.8%; P < 0.05). CGS 21680-response was also greater in HS-eNOS(-/-) (+45.4 +/- A 5.2%) versus NS-eNOS(-/-)(+5.1 +/- A 5.0%; P < 0.05). In HS-eNOS(-/-), the CGS 21680-response was reduced by MS-PPOH (+7.3 +/- A 3.2%; P < 0.05). In NS-eNOS(-/-), the CGS 21680-response was increased by AUDA (+38.2 +/- A 3.3%; P < 0.05) and DDMS (+30.1 +/- A 4.1%; P < 0.05). Compared to NS, HS increased CYP2J2 in eNOS(+/+) (35%; P < 0.05) and eNOS(-/-) (61%; P < 0.05), but decreased sEH in eNOS(+/+) (74%; P < 0.05) and eNOS(-/-) (40%; P < 0.05). Similarly, CYP4A decreased in HS-eNOS(+/+) (35%; P < 0.05) and HS-eNOS(-/-) (34%; P < 0.05). These data suggest that NS causes reduced-vasodilation in both eNOS(+/+) and eNOS(-/-) via sEH and CYP4A. However, HS triggers possible A(2A)AR-induced relaxation through CYP epoxygenase in both eNOS(+/+) and eNOS(-/-). C1 [Nayeem, Mohammed A.; Boegehold, Matthew A.] W Virginia Univ, Dept Physiol & Pharmacol, Ctr Cardiovasc & Resp Sci, Morgantown, WV 26506 USA. [Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, RTP, Durham, NC 27709 USA. [Falck, John R.] UTSWMC, Dept Biochem, Dallas, TX 75390 USA. RP Nayeem, MA (reprint author), W Virginia Univ, Dept Physiol & Pharmacol, Ctr Cardiovasc & Resp Sci, 3051 Robert C Byrd Hlth Sci Ctr N,1 Med Ctr Dr,PO, Morgantown, WV 26506 USA. EM mnayeem@hsc.wvu.edu RI Nayeem, Mohammed/A-3949-2017; OI Nayeem, Mohammed/0000-0002-7827-4760; Falck, John/0000-0002-9219-7845 FU NIEHS/NIH [Z01 ES025034] FX The authors would like to thank Dr. Mustafa for his support (HL 027339 and MAN is Co-Investigator in HL 094447), AHA 2250298 (MAB), GM 31278 (JRF), and the Intramural Research Program of the NIEHS/NIH-Z01 ES025034 (DCZ). NR 49 TC 9 Z9 9 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD APR PY 2011 VL 350 IS 1-2 BP 101 EP 111 DI 10.1007/s11010-010-0686-0 PG 11 WC Cell Biology SC Cell Biology GA 735FM UT WOS:000288398800010 PM 21161333 ER PT J AU Chen, CF He, XL Arslan, AD Mo, YY Reinhold, WC Pommier, Y Beck, WT AF Chen, Cheng-Fen He, Xiaolong Arslan, Ahmet Dirim Mo, Yin-Yuan Reinhold, William C. Pommier, Yves Beck, William T. TI Novel Regulation of Nuclear Factor-YB by miR-485-3p Affects the Expression of DNA Topoisomerase II alpha and Drug Responsiveness SO MOLECULAR PHARMACOLOGY LA English DT Article ID HUMAN CANCER; CATALYTIC INHIBITOR; LEUKEMIC-CELLS; RESISTANCE; MICRORNAS; PROTEIN; GENE; TRANSCRIPTION; GROWTH; PROLIFERATION AB Nuclear factor (NF)-YB, a subunit of the transcription factor nuclear factor Y (NF-Y) complex, binds and activates CCAAT-containing promoters. Our previous work suggested that NF-YB may be a mediator of topoisomerase II alpha (Top2 alpha), working through the Top2 alpha promoter. DNA topoisomerase II (Top2) is an essential nuclear enzyme and the primary target for several clinically important anticancer drugs. Our teniposide-resistant human lymphoblastic leukemia CEM cells (CEM/VM-1-5) express reduced Top2 alpha protein compared with parental CEM cells. To study the regulation of Top2 alpha during the development of drug resistance, we found that NF-YB protein expression is increased in CEM/VM-1-5 cells compared with parental CEM cells. This further suggests that increased NF-YB may be a negative regulator of Top2 alpha in CEM/VM-1-5 cells. We asked what causes the up-regulation of NF-YB in CEM/VM-1-5 cells. We found by microRNA profiling that hsa-miR-485-3p is lower in CEM/VM-1-5 cells compared with CEM cells. MicroRNA target prediction programs revealed that the 3'-untranslated region (3'-UTR) of NF-YB harbors a putative hsa-miR-485-3p binding site. We thus hypothesized that hsa-miR-485-3p mediates drug responsiveness by decreasing NF-YB expression, which in turn negatively regulates Top2 alpha expression. To test this, we overexpressed miR-485-3p in CEM/VM-1-5 cells and found that this led to reduced expression of NF-YB, a corresponding up-regulation of Top2 alpha, and increased sensitivity to the Top2 inhibitors. Results in CEM cells were replicated in drug-sensitive and -resistant human rhabdomyosarcoma Rh30 cells, suggesting that our findings represent a general phenomenon. Ours is the first study to show that miR-485-3p mediates Top2 alpha down-regulation in part by altered regulation of NF-YB. C1 [Chen, Cheng-Fen; He, Xiaolong; Beck, William T.] Univ Illinois, Dept Biopharmaceut Sci, Chicago, IL 60612 USA. [Beck, William T.] Univ Illinois, Ctr Canc, Chicago, IL 60612 USA. [Mo, Yin-Yuan] So Illinois Univ, Sch Med, Dept Med Microbiol, Springfield, IL USA. [Reinhold, William C.; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Beck, WT (reprint author), Univ Illinois, Dept Biopharmaceut Sci, 833 S Wood St MC 865, Chicago, IL 60612 USA. EM wtbeck@uic.edu FU National Institutes of Health National Cancer Institute [CA40570]; University of Illinois at Chicago; National Institutes of Health National Center for Research Resources [C06-RR15482] FX This work was supported by the National Institutes of Health National Cancer Institute [Grant CA40570]; the University of Illinois at Chicago; and the National Institutes of Health National Center for Research Resources [Grant C06-RR15482]. NR 38 TC 25 Z9 28 U1 0 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD APR PY 2011 VL 79 IS 4 BP 735 EP 741 DI 10.1124/mol.110.069633 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 737BA UT WOS:000288541200011 PM 21252292 ER PT J AU Backus, KM Boshoff, HL Barry, CS Boutureira, O Patel, MK D'Hooge, F Lee, SS Via, LE Tahlan, K Barry, CE Davis, BG AF Backus, Keriann M. Boshoff, Helena L. Barry, Conor S. Boutureira, Omar Patel, Mitul K. D'Hooge, Francois Lee, Seung Seo Via, Laura E. Tahlan, Kapil Barry, Clifton E., III Davis, Benjamin G. TI Uptake of unnatural trehalose analogs as a reporter for Mycobacterium tuberculosis SO NATURE CHEMICAL BIOLOGY LA English DT Article ID CORD FACTOR; ANTIGEN 85C; CELL-WALL; BIOSYNTHESIS; BIOGENESIS; SMEGMATIS; GLYCOSYLATION; MACROPHAGES; TRAFFICKING; NEUTROPHILS AB The detection of tuberculosis currently relies upon insensitive and unspecific techniques; newer diagnostics would ideally co-opt specific bacterial processes to provide real-time readouts. The trehalose mycolyltransesterase enzymes (antigens 85A, 85B and 85C (Ag85A, Ag85B, Ag85C)) serve as essential mediators of cell envelope function and biogenesis in Mycobacterium tuberculosis. Through the construction of a systematically varied sugar library, we show here that Ag85 enzymes have exceptionally broad substrate specificity. This allowed exogenously added synthetic probes to be specifically incorporated into M. tuberculosis growing in vitro and within macrophages. Even bulky substituents, such as a fluorescein-containing trehalose probe (FITC-trehalose), were incorporated by growing bacilli, thereby producing fluorescent bacteria; microscopy revealed selective labeling of poles and membrane. Addition of FITC-trehalose to M. tuberculosis-infected macrophages allowed selective, sensitive detection of M. tuberculosis within infected mammalian macrophages. These studies suggest that analogs of trehalose may prove useful as probes of function and for other imaging modalities. C1 [Backus, Keriann M.; Barry, Conor S.; Boutureira, Omar; Patel, Mitul K.; D'Hooge, Francois; Lee, Seung Seo; Davis, Benjamin G.] Univ Oxford, Dept Chem, Chem Res Lab, Oxford, England. [Backus, Keriann M.; Boshoff, Helena L.; Via, Laura E.; Tahlan, Kapil; Barry, Clifton E., III] US Natl Inst Allergy & Infect Dis, TB Res Sect, Lab Clin Infect Dis, Bethesda, MD USA. RP Backus, KM (reprint author), Univ Oxford, Dept Chem, Chem Res Lab, Oxford, England. EM cbarry@niaid.nih.gov; ben.davis@chem.ox.ac.uk RI D'Hooge, Francois/C-3571-2009; Barry, III, Clifton/H-3839-2012; Boutureira, Omar/I-9045-2014; Davis, Benjamin/C-5281-2011; OI Boutureira, Omar/0000-0002-0768-8309; Davis, Benjamin/0000-0002-5056-407X; Via, Laura/0000-0001-6074-9521; Lee, Seung/0000-0002-8598-3303 FU Colorado State "Tuberculosis Vaccine Testing and Research Materials"; US National Institutes of Health; US National Institute of Allergy and Infectious Disease; Rhodes Trust; Marie Curie Intra European Fellowship; Engineering and Physical Sciences Research Council; Bill and Melinda Gates Foundation FX We thank T. Claridge, B. Odell and T. Jackson for assistance with NMR spectra and C. Sparrow, J. McCullagh and R. Procter for their assistance with mass spectrometry. O. Schwartz, L. Koo, M. Gastinger, S. Becker and J. Kabat provided tremendous assistance on all imaging of M. tuberculosis. We thank the Colorado State "Tuberculosis Vaccine Testing and Research Materials" Contract (Colorado State University, Fort Collins) and G. J. Davies (University of York) for providing Ag85 and OtsA plasmids, respectively. We thank A. Sher (US National Institute of Allergy and Infectious Disease, US National Institutes of Health) for M. bovis BCG expressing DSRed1 and T. Oh (Yonsei University) for H37Rv carrying the mCherry-PMV261 plasmid. This study was supported (in part) by the Intramural Research Program of the US National Institutes of Health, the US National Institute of Allergy and Infectious Disease (C. E. B.), the Rhodes Trust (K. M. B.), a Marie Curie Intra European Fellowship (O. B.), the Engineering and Physical Sciences Research Council (Platform Grant to B. G. D.) and the Bill and Melinda Gates Foundation through the Tuberculosis Drug Accelerator Program (C. E. B., B. G. D.). NR 47 TC 62 Z9 62 U1 1 U2 35 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1552-4450 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD APR PY 2011 VL 7 IS 4 BP 228 EP 235 DI 10.1038/NCHEMBIO.539 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 737CC UT WOS:000288545000011 PM 21378984 ER PT J AU Konkel, JE Maruyama, T Carpenter, AC Xiong, YM Zamarron, BF Hall, BE Kulkarni, AB Zhang, P Bosselut, R Chen, WJ AF Konkel, Joanne E. Maruyama, Takashi Carpenter, Andrea C. Xiong, Yumei Zamarron, Brian F. Hall, Bradford E. Kulkarni, Ashok B. Zhang, Pin Bosselut, Remy Chen, WanJun TI Control of the development of CD8 alpha alpha(+) intestinal intraepithelial lymphocytes by TGF-beta SO NATURE IMMUNOLOGY LA English DT Article ID REGULATORY T-CELLS; LINEAGE DIFFERENTIATION; IMMUNE-RESPONSES; RUNX PROTEINS; EXPRESSION; CD8; MICE; GROWTH; SELECTION; ANTIGEN AB The molecular mechanisms that direct the development of TCR alpha beta(+)CD8 alpha alpha(+) intestinal intraepithelial lymphocytes (IELs) are not thoroughly understood. Here we show that transforming growth factor-beta (TGF-beta) controls the development of TCR alpha beta(+)CD8 alpha alpha(+) IELs. Mice with either a null mutation in the gene encoding TGF-beta 1 or T cell-specific deletion of TGF-beta receptor I lacked TCR alpha beta(+)CD8 alpha alpha(+) IELs, whereas mice with transgenic overexpression of TGF-beta 1 had a larger population of TCR alpha beta(+)CD8 alpha alpha(+) IELs. We observed defective development of the TCR alpha beta(+)CD8 alpha alpha(+) IEL thymic precursors (CD4(-)CD8(-)TCR alpha beta(+)CD5(+)) in the absence of TGF-beta. In addition, we found that TGF-beta signaling induced CD8 alpha expression in TCR alpha beta(+)CD8 alpha alpha(+) IEL thymic precursors and induced and maintained CD8 alpha expression in peripheral populations of T cells. Our data demonstrate a previously unrecognized role for TGF-beta in the development of TCR alpha beta(+)CD8 alpha alpha(+) IELs and the expression of CD8 alpha in T cells. C1 [Konkel, Joanne E.; Maruyama, Takashi; Zamarron, Brian F.; Zhang, Pin; Chen, WanJun] Natl Inst Dent & Craniofacial Res, Mucosal Immunol Unit, Oral Infect & Immun Branch, NIH, Bethesda, MD USA. [Carpenter, Andrea C.; Xiong, Yumei; Bosselut, Remy] NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA. [Hall, Bradford E.; Kulkarni, Ashok B.] Natl Inst Dent & Craniofacial Res, Funct Genom Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD USA. RP Chen, WJ (reprint author), Natl Inst Dent & Craniofacial Res, Mucosal Immunol Unit, Oral Infect & Immun Branch, NIH, Bethesda, MD USA. EM wchen@dir.nidcr.nih.gov FU National Institutes of Health, National Institute of Dental and Craniofacial Research; National Cancer Institute, Center for Cancer Research FX We thank G. McGrady and S. Wahl (National Institute of Dental and Craniofacial Research, National Institutes of Health) for Tgfb1-/- mice, and E. Stregevsky and J. Simone for technical assistance. Supported by the Intramural Research Program of the National Institutes of Health, National Institute of Dental and Craniofacial Research and National Cancer Institute, Center for Cancer Research. NR 49 TC 50 Z9 51 U1 2 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD APR PY 2011 VL 12 IS 4 BP 312 EP U118 DI 10.1038/ni.1997 PG 9 WC Immunology SC Immunology GA 737UJ UT WOS:000288593400009 PM 21297643 ER PT J AU Wan, FY Weaver, A Gao, XF Bern, M Hardwidge, PR Lenardo, MJ AF Wan, Fengyi Weaver, Amanda Gao, Xiaofei Bern, Michael Hardwidge, Philip R. Lenardo, Michael J. TI IKK beta phosphorylation regulates RPS3 nuclear translocation and NF-kappa B function during infection with Escherichia coli strain O157:H7 SO NATURE IMMUNOLOGY LA English DT Article ID RIBOSOMAL-PROTEIN S3; CASEIN KINASE-II; TYROSINE PHOSPHORYLATION; DNA-REPAIR; ALPHA; ACTIVATION; TRANSCRIPTION; COMPLEXES; SUBUNIT; CELLS AB NF-kappa B is a major gene regulator in immune responses, and ribosomal protein S3 (RPS3) is an NF-kappa B subunit that directs specific gene transcription. However, it is unknown how nuclear translocation of RPS3 is regulated. Here we report that phosphorylation of RPS3 Ser209 by the kinase IKK beta was crucial for nuclear localization of RPS3 in response to activating stimuli. Moreover, virulence protein NleH1 of the foodborne pathogen Escherichia coli strain O157:H7 specifically inhibited phosphorylation of RPS3 Ser209 and blocked RPS3 function, thereby promoting bacterial colonization and diarrhea but resulting in less mortality in a gnotobiotic piglet-infection model. Thus, the IKK beta-dependent modification of a specific amino acid in RPS3 promoted specific NF-kappa B functions that underlie the molecular pathogenetic mechanisms of E. coli O157:H7. C1 [Wan, Fengyi; Weaver, Amanda; Bern, Michael; Lenardo, Michael J.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Wan, Fengyi] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biochem & Mol Biol, Baltimore, MD USA. [Gao, Xiaofei; Hardwidge, Philip R.] Univ Kansas, Med Ctr, Dept Microbiol Mol Genet & Immunol, Kansas City, KS 66103 USA. RP Lenardo, MJ (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM lenardo@nih.gov FU US National Institutes of Health [R00CA137171, P20 RR016443, R03AI076227, R56AI087686]; Division of Intramural Research of the National Institute of Allergy and Infectious Diseases of the US National Institutes of Health FX We thank T. Huxford (San Diego State University) and C. Wu (National Cancer Institute) for Flag-tagged SSEE and SSAA IKK beta mutants; U. Siebenlist (National Institute of Allergy and Infectious Diseases) for the hemagglutinin-tagged SSAA I kappa B alpha mutant; M. Biancalana (National Institute of Allergy and Infectious Diseases) for recombinant RPS3 protein with the tag cleaved; S. Porcella for DNA sequencing; O. Schwartz, L. Koo and S. Becker for assistance with fluorescence microscopy; and D. Levens, A. Snow and U. Siebenlist for critical reading of the manuscript. Supported by the US National Institutes of Health (R00CA137171 to F.W., a subaward of P20 RR016443, R03AI076227 and R56AI087686 to P.R.H.) and the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases of the US National Institutes of Health. NR 46 TC 54 Z9 55 U1 0 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD APR PY 2011 VL 12 IS 4 BP 335 EP U119 DI 10.1038/ni.2007 PG 10 WC Immunology SC Immunology GA 737UJ UT WOS:000288593400012 PM 21399639 ER PT J AU Kravitz, DJ Saleem, KS Baker, CI Mishkin, M AF Kravitz, Dwight J. Saleem, Kadharbatcha S. Baker, Chris I. Mishkin, Mortimer TI A new neural framework for visuospatial processing SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID POSTERIOR PARIETAL CORTEX; SPATIAL WORKING-MEMORY; SHORT-TERM-MEMORY; PURE TOPOGRAPHICAL DISORIENTATION; MEDIAL PARIETOOCCIPITAL CORTEX; MONKEY RETROSPLENIAL CORTEX; PARAHIPPOCAMPAL PLACE AREA; SACCADIC EYE-MOVEMENTS; MACAQUE MONKEY; RHESUS-MONKEY AB The division of cortical visual processing into distinct dorsal and ventral streams is a key framework that has guided visual neuroscience. The characterization of the ventral stream as a 'What' pathway is relatively uncontroversial, but the nature of dorsal stream processing is less clear. Originally proposed as mediating spatial perception ('Where'), more recent accounts suggest it primarily serves non-conscious visually guided action ('How'). Here, we identify three pathways emerging from the dorsal stream that consist of projections to the prefrontal and premotor cortices, and a major projection to the medial temporal lobe that courses both directly and indirectly through the posterior cingulate and retrosplenial cortices. These three pathways support both conscious and non-conscious visuospatial processing, including spatial working memory, visually guided action and navigation, respectively. C1 [Kravitz, Dwight J.; Baker, Chris I.] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. [Saleem, Kadharbatcha S.; Mishkin, Mortimer] NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Kravitz, DJ (reprint author), NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. EM kravitzd@mail.nih.gov RI Kravitz, Dwight/B-8430-2012; OI Saleem, Kadharbatcha S/0000-0002-4450-9234; Baker, Chris/0000-0001-6861-8964 FU US National Institutes of Health (NIH), National Institute of Mental Health (NIMH) FX We wish to thank L. Ungerleider, M. Goodale, A. Martin, D. Leopold, M. Behrmann and D. Tsao for their extremely helpful comments. This research was supported by the Intramural Program of the US National Institutes of Health (NIH), National Institute of Mental Health (NIMH). NR 203 TC 336 Z9 339 U1 17 U2 114 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0048 J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD APR PY 2011 VL 12 IS 4 BP 217 EP 230 DI 10.1038/nrn3008 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 736ZS UT WOS:000288535600011 PM 21415848 ER PT J AU Li, JX Koek, W Rice, KC France, CP AF Li, Jun-Xu Koek, Wouter Rice, Kenner C. France, Charles P. TI Effects of Direct- and Indirect-Acting Serotonin Receptor Agonists on the Antinociceptive and Discriminative Stimulus Effects of Morphine in Rhesus Monkeys SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE serotonin; morphine; rhesus monkey; antinociception; drug discrimination; drug interaction ID HIGH EFFICACY; ANALGESIA; INHIBITOR; FLUOXETINE; SUBTYPES; MICE; RAT AB Serotonergic (5-HT) systems modulate pain, and drugs acting on 5-HT systems are used with opioids to treat pain. This study examined the effects of 5-HT receptor agonists on the antinociceptive and discriminative stimulus effects of morphine in monkeys. Morphine increased tail-withdrawal latency in a dose-related manner; 5-HT receptor agonists alone increased tail-withdrawal latency at 50 degrees C but not 55 degrees C water. The antinociceptive effects of morphine occurred with smaller doses when monkeys received an indirect-acting (fenfluramine) or direct acting (8-OH-DPAT, F13714, buspirone, quipazine, DOM, and 2C-T-7) agonist. The role of 5-HT receptor subtypes in these interactions was confirmed with selective 5-HT(1A) (WAY100635) and 5-HT(2A) (MDL100907) receptor antagonists. None of the 5-HT drugs had morphine-like discriminative stimulus effects; however, fenfluramine and 5-HT(2A) receptor agonists attenuated the discriminative stimulus effects of morphine and this attenuation was prevented by MDL100907. The 5-HT(1A) receptor agonists did not alter the discriminative stimulus effects of morphine. Thus, 5-HT receptor agonists increase the potency of morphine in an assay of antinociception, even under conditions where 5-HT agonists are themselves without effect (ie, 55 degrees C water), without increasing (and in some cases decreasing) the potency of morphine in a drug discrimination assay. Whereas 5-HT(2A) receptor agonists increase the potency of morphine for antinociception at doses that have no effect on the rate of operant responding, 5-HT(1A) receptor agonists increase the potency of morphine only at doses that eliminate operant responding. These data suggest that drugs acting selectively on 5-HT receptor subtypes could help to improve the use of opioids for treating pain. Neuropsychopharmacology (2011) 36, 940-949; doi:10.1038/npp.2010.232; published online 5 January 2011 C1 [Li, Jun-Xu; Koek, Wouter; France, Charles P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [Koek, Wouter; France, Charles P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Rice, Kenner C.] Natl Inst Drug Abuse, Chem Biol Res Lab, Bethesda, MD USA. [Rice, Kenner C.] NIAAA, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. RP France, CP (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM france@uthscsa.edu RI Li, Jun-Xu/K-9192-2013 FU United States Public Health Service [DA005018]; National Institute on Drug Abuse, National Institutes of Health [K05 DA17918]; National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health; NIDA; Merz Pharmaceuticals; Porsolt & Partners Pharmacology FX We thank Christopher Cruz, Ryan Luna, Maria Hernandez, and Blake Harrington for excellent technical assistance. This work was supported by the United States Public Health Service Grant DA005018. CPF is supported by a Senior Scientist Award from the National Institute on Drug Abuse, National Institutes of Health (K05 DA17918). This research was supported, in part, by the Intramural Research Programs of the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health.; Charles P France has received grant/research support from NIDA, Merz Pharmaceuticals, and Porsolt & Partners Pharmacology. He has severed as a consultant to NIH (study section), Takeda Pharmaceuticals, and Porsolt & Partners Pharmacology. The other authors declare no conflict of interest. NR 22 TC 11 Z9 11 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD APR PY 2011 VL 36 IS 5 BP 940 EP 949 DI 10.1038/npp.2010.232 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 736KM UT WOS:000288493600003 PM 21209613 ER PT J AU Blaylock, BL Gould, RW Banala, A Grundt, P Luedtke, RR Newman, AH Nader, MA AF Blaylock, B. L. Gould, R. W. Banala, A. Grundt, P. Luedtke, R. R. Newman, A. H. Nader, M. A. TI Influence of Cocaine History on the Behavioral Effects of Dopamine D-3 Receptor-Selective Compounds in Monkeys SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE addiction and substance abuse; cocaine; dopamine D-3 receptors; self-administration; reinstatement; nonhuman primates ID RHESUS-MONKEYS; SEEKING BEHAVIOR; D3 RECEPTOR; D2 RECEPTOR; RAPID ASSESSMENT; RAT-BRAIN; CELL-LINE; DRUG; AGONISTS; LIGANDS AB Although dopamine D-3 receptors have been associated with cocaine abuse, little is known about the consequences of chronic cocaine on functional activity of D-3 receptor-preferring compounds. This study examined the behavioral effects of D-3 receptor-selective 4-phenylpiperazines with differing in vitro functional profiles in adult male rhesus monkeys with a history of cocaine self-administration and controls. In vitro assays found that PG 619 (N-(3-hydroxy-4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)-4-(pyridin-2-yl)benzamide HCl) was a potent D-3 antagonist in the mitogenesis assay, but a fully efficacious agonist in the adenylyl cyclase assay, NGB 2904 (N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butyl)-9H-fluorene-2-carboxamide HCl) was a selective D-3 antagonist, whereas CJB 090 (N-(4-(4-(2,3-dichlorophenyl) piperazin-1-yl) butyl)-4-(pyridin-2-yl) benzamide HCl) exhibited a partial agonist profile in both in vitro assays. In behavioral studies, the D-3 preferential agonist quinpirole (0.03-1.0 mg/kg, i.v.) dose-dependently elicited yawns in both groups of monkeys. PG 619 and CJB 090 elicited yawns only in monkeys with an extensive history of cocaine, whereas NGB 2904 did not elicit yawns, but did antagonize quinpirole and PG 619-elicited yawning in cocaine-history monkeys. In another experiment, doses of PG 619 that elicited yawns did not alter response rates in monkeys self-administering cocaine (0.03-0.3 mg/kg per injection). Following saline extinction, cocaine (0.1 mg/kg) and quinpirole (0.1 mg/kg), but not PG 619 (0.1 mg/kg), reinstated cocaine-seeking behavior. When given before a cocaine prime, PG 619 decreased cocaine-elicited reinstatement. These findings suggest that (1) an incongruence between in vitro and in vivo assays, and (2) a history of cocaine self-administration can affect in vivo efficacy of D-3 receptor-preferring compounds PG 619 and CJB 090, which appear to be dependent on the behavioral assay. Neuropsychopharmacology (2011) 36, 1104-1113; doi:10.1038/npp.2010.248; published online 2 February 2011 C1 [Blaylock, B. L.; Gould, R. W.; Nader, M. A.] Wake Forest Univ, Dept Physiol & Pharmacol, Sch Med, Winston Salem, NC 27157 USA. [Banala, A.; Grundt, P.; Newman, A. H.] Natl Inst Drug Abuse, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD USA. [Luedtke, R. R.] Univ N Texas Hlth Sci Ctr, Dept Pharmacol & Neurosci, Ft Worth, TX USA. RP Nader, MA (reprint author), Wake Forest Univ, Dept Physiol & Pharmacol, Sch Med, 546 NRC,Med Ctr Blvd, Winston Salem, NC 27157 USA. EM mnader@wfubmc.edu FU National Institute on Drug Abuse [R01 DA12460] FX We thank Tonya Calhoun and Susan Nader for excellent technical assistance. This research was supported by the National Institute on Drug Abuse Grant R01 DA12460 (to MAN) and by the NIDA Intramural Research Program (to AHN). NR 51 TC 17 Z9 17 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD APR PY 2011 VL 36 IS 5 BP 1104 EP 1113 DI 10.1038/npp.2010.248 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 736KM UT WOS:000288493600017 PM 21289600 ER PT J AU Song, HT Jordan, EK Lewis, BK Gold, E Liu, W Frank, JA AF Song, Ho-Taek Jordan, Elaine K. Lewis, Bobbi K. Gold, Eric Liu, Wei Frank, Joseph A. TI Quantitative T-2* imaging of metastatic human breast cancer to brain in the nude rat at 3 T SO NMR IN BIOMEDICINE LA English DT Article DE MRI; quantification; cellular tracking; T-2* map; histogram; brain metastasis; breast cancer; superparamagnetic iron oxide (SPIO); dormant breast cancer cell ID MR CONTRAST AGENTS; IN-VIVO TRACKING; MAGNETIC-RESONANCE TRACKING; IRON-OXIDE NANOPARTICLES; SINGLE MAMMALIAN-CELLS; LABELED STEM-CELLS; MULTIPLE-SCLEROSIS; PROGENITOR CELLS; CELLULAR MRI; TRANSFECTION AGENTS AB This study uses quantitative T-2* imaging to track ferumoxides-protamine sulfate (FEPro)-labeled MDA-MB-231BR-Luc (231BRL) human breast cancer cells that metastasize to the nude rat brain. Four cohorts of nude rats were injected intracardially with FEPro-labeled, unlabeled or tumor necrosis factor-related apoptosis-inducing ligand(TRAIL)-treated (to induce apoptosis) 231BRL cells, or saline, in order to develop metastatic breast cancer in the brain. The heads of the rats were imaged serially over 3-4 weeks using gradient multi-echo and turbo spin-echo pulse sequences at 3 T with a solenoid receive-only 4-cm-diameter coil. Quantitative T-2* maps of the whole brain were obtained by the application of single-exponential fitting to the signal intensity of T-2* images, and the distribution of T-2* values in brain voxels was calculated. MRI findings were correlated with Prussian blue staining and immunohistochemical staining for iron in breast cancer and macrophages. Quantitative analysis of T-2* from brain voxels demonstrated a significant shift to lower values following the intracardiac injection of FEPro-labeled 231BRL cells, relative to animals receiving unlabeled cells, apoptotic cells or saline. Quartile analysis based on the T-2* distribution obtained from brain voxels demonstrated significant differences (p < 0.0083) in the number of voxels with T-2* values in the ranges 10-35ms (Q1), 36-60ms (Q2) and 61-86ms (Q3) from 1 day to 3 weeks post-infusion of labeled 231BRL cells, compared with baseline scans. There were no significant differences in the distribution of T-2* obtained from serial MRI in rats receiving unlabeled or TRAIL-treated cells or saline. Histologic analysis demonstrated isolated Prussian blue-positive breast cancer cells scattered in the brains of rats receiving labeled cells, relative to animals receiving unlabeled or apoptotic cells. Quantitative T-2* analysis of FEPro-labeled metastasized cancer cells was possible even after the hypointense voxels were no longer visible on T-2*-weighted images. Published in 2010 by John Wiley & Sons, Ltd. C1 [Song, Ho-Taek; Jordan, Elaine K.; Lewis, Bobbi K.; Gold, Eric; Liu, Wei; Frank, Joseph A.] NIH, Frank Lab, Ctr Clin, Bethesda, MD 20892 USA. [Song, Ho-Taek] Yonsei Univ, Coll Med, Dept Radiol, Seoul, South Korea. [Liu, Wei] Philips Res N Amer, Briarcliff Manor, NY USA. [Frank, Joseph A.] Natl Inst Biomed Imaging & Bioengn, Intramural Res Program, NIH, Bethesda, MD USA. RP Song, HT (reprint author), NIH, Frank Lab, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. FU Clinical Center, National Institutes of Health, Bethesda, MD, USA FX This research was supported by the Intramural Research Program, Clinical Center, National Institutes of Health, Bethesda, MD, USA. We would also like to acknowledge Philips Medical Systems for providing the radiofrequency coil as part of a cooperative research and development agreement. NR 54 TC 8 Z9 8 U1 0 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0952-3480 J9 NMR BIOMED JI NMR Biomed. PD APR PY 2011 VL 24 IS 3 BP 325 EP 334 DI 10.1002/nbm.1596 PG 10 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA 735GD UT WOS:000288400500013 PM 20949637 ER PT J AU Yu, YK AF Yu, Yi-Kuo TI Challenges of Information Retrieval and Evaluation in Data-Centric Biology SO OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY LA English DT Letter C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Yu, YK (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, 9000 Rockville Pike,MSC 3829, Bethesda, MD 20894 USA. EM yyu@ncbi.nlm.nih.gov FU Intramural NIH HHS NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1536-2310 J9 OMICS JI OMICS PD APR PY 2011 VL 15 IS 4 BP 239 EP 240 DI 10.1089/omi.2011.0026 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 746XC UT WOS:000289281300011 PM 21476849 ER PT J AU Assa'ad, A AF Assa'ad, Amal TI THIS ISSUE: Allergy, Asthma, and Immunology SO PEDIATRIC ANNALS LA English DT Editorial Material C1 [Assa'ad, Amal] Cincinnati Childrens Hosp Med Ctr, AI Div, Cincinnati, OH USA. [Assa'ad, Amal] Univ Cincinnati, Coll Med, Cincinnati, OH 45221 USA. [Assa'ad, Amal] NIH, Bethesda, MD 20892 USA. RP Assa'ad, A (reprint author), Cincinnati Childrens Hosp Med Ctr, AI Div, Cincinnati, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0090-4481 J9 PEDIATR ANN JI Pediatr. Annu. PD APR PY 2011 VL 40 IS 4 BP 179 EP 180 DI 10.3928/00904481-20110316-02 PG 2 WC Pediatrics SC Pediatrics GA 964ZL UT WOS:000305735200002 PM 21485991 ER PT J AU Smirnovas, V Baron, GS Daniell, OK Raymond, GJ Caughey, B Surewicz, WK AF Smirnovas, Vytautas Baron, Gerald S. Daniell, Offerdahl K. Raymond, Gregory J. Caughey, Byron Surewicz, Witold K. TI Towards Understanding the Structure of PrPSc Conformer Associated with Prion Infectivity SO PRION LA English DT Meeting Abstract C1 [Smirnovas, Vytautas; Surewicz, Witold K.] Case Western Reserve Univ, Dept Physiol & Biophys, Cleveland, OH 44106 USA. [Baron, Gerald S.; Daniell, Offerdahl K.; Raymond, Gregory J.; Caughey, Byron] NIAID, Lab Persistent Viral Infect, NIH, Hamilton, MT USA. EM wks3@case.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR-JUN PY 2011 VL 5 SU S MA Oral.13 BP 6 EP 6 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA V34DE UT WOS:000209066300014 ER PT J AU Baron, GS Hughson, AG Raymond, GJ Offerdahl, DK Barton, KA Raymond, LD Dorward, DW Caughey, B AF Baron, Gerald S. Hughson, Andrew G. Raymond, Gregory J. Offerdahl, Danielle K. Barton, Kelly A. Raymond, Lynne D. Dorward, David W. Caughey, Byron TI Effect of Glycans and GPI Anchor on Strain Dependent Conformations of Scrapie Prion Protein: Improved Purifications and IR Spectra SO PRION LA English DT Meeting Abstract C1 [Baron, Gerald S.; Hughson, Andrew G.; Raymond, Gregory J.; Offerdahl, Danielle K.; Barton, Kelly A.; Raymond, Lynne D.; Dorward, David W.; Caughey, Byron] NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. EM gbaron@niaid.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR-JUN PY 2011 VL 5 SU S MA Oral.17 BP 8 EP 8 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA V34DE UT WOS:000209066300018 ER PT J AU Caughey, B AF Caughey, Byron TI Structural Analyses and Detection of TSE Prions Using Seeded Conversion of Recombinant PrP SO PRION LA English DT Meeting Abstract C1 [Caughey, Byron] NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR-JUN PY 2011 VL 5 SU S MA Oral.19 BP 8 EP 8 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA V34DE UT WOS:000209066300019 ER PT J AU McGuire, LI Peden, AH Appleford, N Mallinson, G Orru, C Wilham, J Raymond, G Andrews, M Head, MW Caughey, B Will, R Knight, R Green, A AF McGuire, Lynne I. Peden, Alexander H. Appleford, Nigel Mallinson, Gary Orru, Christina Wilham, Jason Raymond, Greg Andrews, Mary Head, Mark W. Caughey, Byron Will, Robert Knight, Richard Green, Alison TI Prion Seeding Activity in Cerebrospinal Fluid from Sporadic Creutzfeldt-Jakob Disease Patients Using Real-Time QuIC Analysis: A Potential New Diagnostic Test? SO PRION LA English DT Meeting Abstract C1 [McGuire, Lynne I.; Peden, Alexander H.; Andrews, Mary; Head, Mark W.; Will, Robert; Knight, Richard; Green, Alison] Univ Edinburgh, NCJDSU, Edinburgh, Midlothian, Scotland. [Appleford, Nigel; Mallinson, Gary] Bristol Inst Transfus Sci NHS Blood & Transplant, Bristol, Avon, England. [Orru, Christina; Wilham, Jason; Raymond, Greg; Caughey, Byron] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT USA. EM Imcguir1@staffmail.ed.ac.uk NR 2 TC 1 Z9 1 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR-JUN PY 2011 VL 5 SU S MA Oral.42 BP 18 EP 18 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA V34DE UT WOS:000209066300040 ER PT J AU Barton, KA Orru, C Caughey, B AF Barton, Kelly A. Orru, Christina Caughey, Byron TI Use of Plasminogen to Isolate Prions from Biological Samples SO PRION LA English DT Meeting Abstract C1 NIH, Rocky Mt Labs, Hamilton, MT USA. [Barton, Kelly A.; Orru, Christina; Caughey, Byron] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT USA. EM bartonk@niaid.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR-JUN PY 2011 VL 5 SU S MA Bio.015 BP 26 EP 26 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA V34DE UT WOS:000209066300057 ER PT J AU Taubner, LM Bienkiewicz, EA Copie, V Caughey, B AF Taubner, Laura M. Bienkiewicz, Ewa A. Copie, Valerie Caughey, Byron TI Structure of the Flexible Amino-Terminal Domain of Prion Protein Bound to a Sulfated Glycan SO PRION LA English DT Meeting Abstract C1 [Bienkiewicz, Ewa A.] Florida State Univ, Tallahasee, FL USA. [Taubner, Laura M.; Caughey, Byron] NIAID, Rocky Mt Labs, NIH, Hamilton, MO USA. [Copie, Valerie] Montana State Univ, Bozeman, MO USA. EM ewa.bienkiewicz@med.fsu.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR-JUN PY 2011 VL 5 SU S MA Bio.022 BP 29 EP 29 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA V34DE UT WOS:000209066300064 ER PT J AU Lowe, DC Wilham, JM Watschke, CR Wiley, JA Caughey, B Bessen, RA AF Lowe, Diana C. Wilham, Jason M. Watschke, Christopher R. Wiley, James A. Caughey, Byron Bessen, Richard A. TI Accelerated Prion Shedding Following Damage to the Olfactory Epithelium SO PRION LA English DT Meeting Abstract C1 [Lowe, Diana C.; Watschke, Christopher R.; Wiley, James A.; Bessen, Richard A.] Montana State Univ, Bozeman, MT 59717 USA. [Wilham, Jason M.; Caughey, Byron] NIH, Persistent Viral Dis Lab, Hamilton, MT USA. EM diana.lowe@montana.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR-JUN PY 2011 VL 5 SU S MA Bio.097 BP 62 EP 62 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA V34DE UT WOS:000209066300139 ER PT J AU Ostapchenko, VG Tycko, R Savtchenko, RS Baskakov, IV AF Ostapchenko, Valeriy G. Tycko, Robert Savtchenko, Regina S. Baskakov, Ilia V. TI Architecture of Prion Protein Fibrils SO PRION LA English DT Meeting Abstract C1 [Ostapchenko, Valeriy G.] Univ Western Ontario, Schulich Sch Med, Robarts Res Inst, London, ON, Canada. [Tycko, Robert] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. [Ostapchenko, Valeriy G.; Savtchenko, Regina S.; Baskakov, Ilia V.] Univ Maryland, Dept Anat & Neurobiol, Ctr Biomed Engn & Technol, Baltimore, MD 21201 USA. EM vostapc@uwo.ca NR 0 TC 0 Z9 0 U1 0 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR-JUN PY 2011 VL 5 SU S MA Bio.123 BP 73 EP 73 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA V34DE UT WOS:000209066300165 ER PT J AU Peden, AH McGuire, LI Appleford, NE Mallinson, G Caughey, B Wilham, JM Orru, CD Will, RG Knight, RS Ironside, JW Green, AJ Head, MW AF Peden, Alexander H. McGuire, Lynne I. Appleford, Nigel E. Mallinson, Gary Caughey, Byron Wilham, Jason M. Orru, Christina D. Will, Robert G. Knight, Richard S. Ironside, James W. Green, Alison J. Head, Mark W. TI Sensitive and Specific Detection of Sporadic Creutzfeldt-Jakob Disease Brain Prion Protein Using Real-Time Quaking Induced Conversion SO PRION LA English DT Meeting Abstract C1 [Peden, Alexander H.; McGuire, Lynne I.; Will, Robert G.; Knight, Richard S.; Ironside, James W.; Green, Alison J.; Head, Mark W.] Natl Creutzfeldt Jakob Dis Surveillance Unit, Edinburgh, Midlothian, Scotland. Natl Blood Serv, Bristol Inst Transfus Sci, Bristol, Avon, England. [Caughey, Byron; Wilham, Jason M.; Orru, Christina D.] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, Hamilton, MT USA. EM A.Peden@ed.ac.uk NR 0 TC 0 Z9 0 U1 0 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR-JUN PY 2011 VL 5 SU S MA Bio.127 BP 75 EP 75 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA V34DE UT WOS:000209066300169 ER PT J AU Motzkus, D Schulz-Schaeffer, W Beekes, M Schatzl, HM Jirik, FR Schmadicke, AC Daus, M Breyer, J Gilch, SV Comoy, E Graham, C Deslys, JP Richt, JA Race, B Czub, S AF Motzkus, Dirk Schulz-Schaeffer, Walter Beekes, Michael Schaetzl, Hermann M. Jirik, Frank R. Schmaedicke, Ann-Christin Daus, Martin Breyer, Johanna Gilch, Sabine V. Comoy, Emmanuel Graham, Catherine Deslys, Jean-Phillipe Richt, Juergen A. Race, Brent Czub, Stefanie TI Transmission of CWD to Non-Human Primates: Interim Results of a Comprehensive Study on the Transmissibility to Humans SO PRION LA English DT Meeting Abstract C1 [Motzkus, Dirk; Schmaedicke, Ann-Christin] German Primate Ctr, Gottingen, Germany. [Schulz-Schaeffer, Walter; Breyer, Johanna] Fac Med, Dept Neuropathol, Gottingen, Germany. [Beekes, Michael; Daus, Martin] Robert Koch Inst, Berlin, Germany. [Schaetzl, Hermann M.; Gilch, Sabine V.] Univ Wyoming, Dept Vet Sci & Mol Biol, Laramie, WY 82071 USA. [Jirik, Frank R.] Univ Calgary, Fac Vet Med, Calgary, AB, Canada. [Comoy, Emmanuel; Deslys, Jean-Phillipe] Commissariat Energie Atom, Fontenay Aux Roses, France. [Graham, Catherine; Czub, Stefanie] Canada Food Inspect Agcy, Anim Dis Res Inst, Lethbridge, AB, Canada. [Richt, Juergen A.] Kansas State Univ, Coll Vet Med, Manhattan, KS 66506 USA. [Race, Brent] NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. EM dmotzkus@dpz.eu NR 0 TC 1 Z9 1 U1 0 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR-JUN PY 2011 VL 5 SU S MA Envt.22 BP 107 EP 107 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA V34DE UT WOS:000209066300245 ER PT J AU Abrams, J Schonberger, LB Belay, ED Maddox, RA Leschek, EW Mills, JL Wysowski, DK Fradkin, JE AF Abrams, Joseph Schonberger, Lawrence B. Belay, Ermias D. Maddox, Ryan A. Leschek, Ellen W. Mills, James L. Wysowski, Diane K. Fradkin, Judith E. TI Lower Risk of Creutzfeldt-Jakob Disease in Pituitary Growth Hormone Recipients Initiating Treatment After 1977 SO PRION LA English DT Meeting Abstract C1 [Abrams, Joseph; Schonberger, Lawrence B.; Belay, Ermias D.; Maddox, Ryan A.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Leschek, Ellen W.; Mills, James L.; Fradkin, Judith E.] NIH, Bethesda, MD 20892 USA. [Wysowski, Diane K.] US FDA, Rockville, MD 20857 USA. EM hus4@cdc.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR-JUN PY 2011 VL 5 SU S MA Risk.01 BP 123 EP 123 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA V34DE UT WOS:000209066300279 ER PT J AU Orru, CD Raymond, L Wilharn, J Kuhn, F Schroeder, B Raeber, A Caughey, B AF Orru, Christina D. Raymond, Lynne Wilharn, Jason Kuhn, Franziska Schroeder, Bjoern Raeber, Alex Caughey, Byron TI Improved Prion Detection Using Immunoprecipitation and Enhanced Quaking-Induced Conversion SO PRION LA English DT Meeting Abstract C1 [Orru, Christina D.; Raymond, Lynne; Wilharn, Jason; Caughey, Byron] NIH, Rocky Mt Labs, Hamilton, MT USA. [Kuhn, Franziska; Schroeder, Bjoern; Raeber, Alex] Prionics AG, Zurich, Switzerland. EM orruc@niaid.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR-JUN PY 2011 VL 5 SU S MA Risk.34 BP 136 EP 137 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA V34DE UT WOS:000209066300309 ER PT J AU Shin, BS Acker, MG Kim, JR Maher, KN Arefin, SM Lorsch, JR Dever, TE AF Shin, Byung-Sik Acker, Michael G. Kim, Joo-Ran Maher, Kathryn N. Arefin, Shamsul M. Lorsch, Jon R. Dever, Thomas E. TI Structural integrity of alpha-helix H12 in translation initiation factor eIF5B is critical for 80S complex stability SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE IF2; eIF5B; subunit joining; translation initiation ID TRANSFER-RNA BINDING; C-TERMINAL DOMAIN; FACTOR IF2; BACILLUS-STEAROTHERMOPHILUS; RIBOSOMAL-SUBUNIT; FACTORS 1A; YEAST; SITE; GCN4; FMET-TRNA(FMET) AB Translation initiation factor eIF5B promotes GTP-dependent ribosomal subunit joining in the final step of the translation initiation pathway. The protein resembles a chalice with the alpha-helix H12 forming the stem connecting the GTP-binding domain cup to the domain IV base. Helix H12 has been proposed to function as a rigid lever arm governing domain IV movements in response to nucleotide binding and as a molecular ruler fixing the distance between domain IV and the G domain of the factor. To investigate its function, helix H12 was lengthened or shortened by one or two turns. In addition, six consecutive residues in the helix were substituted by Gly to alter the helical rigidity. Whereas the mutations had minimal impacts on the factor's binding to the ribosome and its GTP binding and hydrolysis activities, shortening the helix by six residues impaired the rate of subunit joining in vitro and both this mutation and the Gly substitution mutation lowered the yield of Met-tRNA(i)(Met) bound to 80S complexes formed in the presence of nonhydrolyzable GTP. Thus, these two mutations, which impair yeast cell growth and enhance ribosome leaky scanning in vivo, impair the rate of formation and stability of the 80S product of subunit joining. These data support the notion that helix H12 functions as a ruler connecting the GTPase center of the ribosome to the P site where Met-tRNA(i)(Met) is bound and that helix H12 rigidity is required to stabilize Met-tRNA(i)(Met) binding. C1 [Shin, Byung-Sik; Kim, Joo-Ran; Maher, Kathryn N.; Arefin, Shamsul M.; Dever, Thomas E.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. [Acker, Michael G.; Lorsch, Jon R.] Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA. RP Dever, TE (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. EM tdever@nih.gov OI Dever, Thomas/0000-0001-7120-9678 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health; American Cancer Society [RSG-03-156-01-GMC] FX We thank Alan Hinnebusch, Antonina Roll-Mecak, and our colleagues in the Dever, Lorsch, and Hinnebusch laboratories for advice and helpful discussions. This work was supported in part by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (T.E.D.), and by American Cancer Society grant RSG-03-156-01-GMC (J.R.L.). NR 37 TC 9 Z9 9 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1355-8382 J9 RNA JI RNA-Publ. RNA Soc. PD APR PY 2011 VL 17 IS 4 BP 687 EP 696 DI 10.1261/rna.2412511 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 737CJ UT WOS:000288545800013 PM 21335519 ER PT J AU Koh, YY Wang, YM Qiu, C Opperman, L Gross, L Hall, TMT Wickens, M AF Koh, Yvonne Yiling Wang, Yeming Qiu, Chen Opperman, Laura Gross, Leah Hall, Traci M. Tanaka Wickens, Marvin TI Stacking interactions in PUF-RNA complexes SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE 3 ' UTRs; RNA decay; RNA-protein interactions; translational regulation; stacking interactions ID PUMILIO-HOMOLOGY DOMAIN; YEAST 3-HYBRID SYSTEM; PROTEIN BINDS RNA; CAENORHABDITIS-ELEGANS; MESSENGER-RNAS; DROSOPHILA-MELANOGASTER; RECOGNITION; SPECIFICITY; TARGETS; REGULATOR AB Stacking interactions between amino acids and bases are common in RNA-protein interactions. Many proteins that regulate mRNAs interact with single-stranded RNA elements in the 3' UTR (3'-untranslated region) of their targets. PUF proteins are exemplary. Here we focus on complexes formed between a Caenorhabditis elegans PUF protein, FBF, and its cognate RNAs. Stacking interactions are particularly prominent and involve every RNA base in the recognition element. To assess the contribution of stacking interactions to formation of the RNA-protein complex, we combine in vivo selection experiments with site-directed mutagenesis, biochemistry, and structural analysis. Our results reveal that the identities of stacking amino acids in FBF affect both the affinity and specificity of the RNA-protein interaction. Substitutions in amino acid side chains can restrict or broaden RNA specificity. We conclude that the identities of stacking residues are important in achieving the natural specificities of PUF proteins. Similarly, in PUF proteins engineered to bind new RNA sequences, the identity of stacking residues may contribute to "target'' versus "off-target'' interactions, and thus be an important consideration in the design of proteins with new specificities. C1 [Koh, Yvonne Yiling; Opperman, Laura; Gross, Leah; Wickens, Marvin] Univ Wisconsin, Dept Biochem, Madison, WI 53706 USA. [Koh, Yvonne Yiling] Univ Wisconsin, Microbiol Doctoral Training Program, Madison, WI 53706 USA. [Wang, Yeming; Qiu, Chen; Hall, Traci M. Tanaka] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Wickens, M (reprint author), Univ Wisconsin, Dept Biochem, 433 Babcock Dr, Madison, WI 53706 USA. EM wickens@biochem.wisc.edu RI Wang, Yeming/C-9082-2013 FU National Institutes of Health, National Institute of Environmental Health Sciences; National Institutes of Health; A*STAR National Science Scholarship from Singapore FX We thank members of the Wickens and Hall laboratories for discussions and suggestions. We appreciate the help of Laura Vanderploeg and Adam Steinberg in the preparation of figures. This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences (to T.H.), and by extramural grants from the National Institutes of Health (to M.W.). Y.Y.K. was supported by the A*STAR National Science Scholarship from Singapore. NR 36 TC 21 Z9 21 U1 2 U2 7 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1355-8382 J9 RNA JI RNA-Publ. RNA Soc. PD APR PY 2011 VL 17 IS 4 BP 718 EP 727 DI 10.1261/rna.2540311 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 737CJ UT WOS:000288545800016 PM 21372189 ER PT J AU Miller, FG Kallmes, DF AF Miller, Franklin G. Kallmes, David F. TI Untitled SO SPINE LA English DT Editorial Material C1 [Miller, Franklin G.] NIH, Dept Bioeth, Bethesda, MD 20892 USA. [Kallmes, David F.] Mayo Clin, Dept Radiol, Rochester, MN USA. RP Miller, FG (reprint author), NIH, Dept Bioeth, Bldg 10, Bethesda, MD 20892 USA. EM fmiller@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD APR 1 PY 2011 VL 36 IS 7 BP 592 EP 592 DI 10.1097/BRS.0b013e3182112a0e PG 1 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 737AH UT WOS:000288537800024 ER PT J AU Insel, TR AF Insel, T. R. TI A bridge to somewhere SO TRANSLATIONAL PSYCHIATRY LA English DT Editorial Material C1 NIMH, NIH, Bethesda, MD 20892 USA. RP Insel, TR (reprint author), NIMH, NIH, Bethesda, MD 20892 USA. EM tinsel@mail.nih.gov NR 0 TC 1 Z9 1 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2158-3188 J9 TRANSL PSYCHIAT JI Transl. Psychiatr. PD APR PY 2011 VL 1 AR e2 DI 10.1038/tp.2011.4 PG 2 WC Psychiatry SC Psychiatry GA 971OB UT WOS:000306212400002 PM 22832390 ER PT J AU Zink, CF Kempf, L Hakimi, S Rainey, CA Stein, JL Meyer-Lindenberg, A AF Zink, C. F. Kempf, L. Hakimi, S. Rainey, C. A. Stein, J. L. Meyer-Lindenberg, A. TI Vasopressin modulates social recognition-related activity in the left temporoparietal junction in humans SO TRANSLATIONAL PSYCHIATRY LA English DT Article DE anxiety; autism; fMRI; social recognition; temporopartietal junction; vasopressin ID ARGININE-VASOPRESSIN; OXYTOCIN; BRAIN; FACES; CIRCUITRY; COGNITION; FAMILIAR; RECEPTOR; EMOTION; MEMORY AB The neuropeptide vasopressin is a key molecular mediator of social behavior in animals and humans, implicated in anxiety and autism. Social recognition, the ability to assess the familiarity of others, is essential for appropriate social interactions and enhanced by vasopressin; however, the neural mechanisms mediating this effect in humans are unknown. Using functional magnetic resonance imaging (fMRI) and an implicit social recognition matching task, we employed a double-blinded procedure in which 20 healthy male volunteers self-administered 40 UI of vasopressin or placebo intranasally, 45 min before performing the matching task in the scanner. In a random-effects fMRI analysis, we show that vasopressin induces a regionally specific alteration in a key node of the theory of mind network, the left temporoparietal junction, identifying a neurobiological mechanism for prosocial neuropeptide effects in humans that suggests novel treatment strategies. Translational Psychiatry (2011) 1, e3; doi:10.1038/tp.2011.2; published online 4 April 2011 C1 [Zink, C. F.; Kempf, L.; Hakimi, S.; Rainey, C. A.; Stein, J. L.; Meyer-Lindenberg, A.] NIMH, Genes Cognit & Psychosis Program, NIH, DHHS, Bethesda, MD 20814 USA. [Meyer-Lindenberg, A.] Cent Inst Mental Hlth, D-6800 Mannheim, Germany. RP Zink, CF (reprint author), NIMH, Genes Cognit & Psychosis Program, NIH, DHHS, 9000 Rockville Pike,Bldg 10,Room 3C101, Bethesda, MD 20814 USA. EM zinkc@mail.nih.gov OI Stein, Jason/0000-0003-4829-0513; Hakimi, Shabnam/0000-0003-4122-6041; Meyer-Lindenberg, Andreas/0000-0001-5619-1123 FU National Institute of Mental Health, NIH FX We thank Mbemba Jabbi, Katherine V Roe and Tiffany A Nash for analysis assistance; Yunxia Tong and Qiang Chen for technical assistance; Timothy O Laumann and Ian J Lent for research assistance; and Gerald Overman and Judith Starling for pharmaceutical management. This research was supported by the Intramural Research Program of the National Institute of Mental Health, NIH. NR 26 TC 12 Z9 12 U1 2 U2 21 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2158-3188 J9 TRANSL PSYCHIAT JI Transl. Psychiatr. PD APR PY 2011 VL 1 AR e3 DI 10.1038/tp.2011.2 PG 5 WC Psychiatry SC Psychiatry GA 971OB UT WOS:000306212400003 PM 22832391 ER PT J AU Shoemaker, L Lenker, J Fuhrer, M Jutai, J Demers, L DeRuyter, F AF Shoemaker, Laura Lenker, James Fuhrer, Marcus Jutai, Jeff Demers, Louise DeRuyter, Frank TI RE: DEVELOPMENT AND EVALUATION OF A NEW TAXONOMY OF MOBILITY-RELATED ASSISTIVE TECHNOLOGY DEVICES SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Letter C1 [Shoemaker, Laura] Regina QuAppelle Hlth Reg, Wascana Rehabil Ctr, Regina, SK, Canada. [Lenker, James] SUNY Buffalo, Sch Publ Hlth & Hlth Profess, Dept Rehabil Sci, Buffalo, NY 14260 USA. [Fuhrer, Marcus] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Columbia, MD USA. [Jutai, Jeff] Univ Ottawa, Bachelors Program Hlth Sci, Ottawa, ON, Canada. [Demers, Louise] Univ Montreal, Fac Med, Sch Rehabil, Montreal, PQ H3C 3J7, Canada. [Demers, Louise] Montreal Geriatr Univ Inst, Montreal, PQ, Canada. [DeRuyter, Frank] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. RP Shoemaker, L (reprint author), Regina QuAppelle Hlth Reg, Wascana Rehabil Ctr, Regina, SK, Canada. NR 1 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD APR PY 2011 VL 90 IS 4 BP 344 EP 344 DI 10.1097/PHM.0b013e31820b191b PG 1 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 731OI UT WOS:000288118600014 ER PT J AU Siegel, MB Naimi, TS Cremeens, JL Nelson, DE AF Siegel, Michael B. Naimi, Timothy S. Cremeens, Jennifer L. Nelson, David E. TI Alcoholic Beverage Preferences and Associated Drinking Patterns and Risk Behaviors Among High School Youth SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID UNITED-STATES; CONSUMPTION; DRINKERS; STUDENTS; EXPOSURE; BEER AB Background: Very little is known about the types of alcoholic beverages preferred by youth in the U.S. and the relationship between beverage preference and demographic and behavioral characteristics of these youth. Purpose: To determine the type of alcoholic beverages consumed by adolescent drinkers and how it varies by drinking patterns. Methods: In 2010, an analysis was performed using 2007 data from the Youth Risk Behavior Survey (YRBS) conducted among public school students in eight states that included a question on the type of alcohol usually consumed. Analysis was restricted to the 7723 youth who reported consuming at least one drink of alcohol in the past 30 days. Beverage type preferences were analyzed by demographic factors, drinking patterns, and other health-risk behaviors. Logistic regression analyses were conducted to examine the correlates of type-specific alcohol consumption. Results: Liquor was the strongly preferred alcoholic beverage of choice (43.8%), followed by beer (19.2%) and malt beverages (17.4%), with a very low preference for wine (3.7%) or wine coolers (3.4%). A higher preference for liquor or beer was observed among older youth, among those with a riskier pattern of alcohol consumption (e.g., greater frequency of consumption, binge drinking, or drinking and driving), and among youth who engaged in other risk behaviors. Conclusions: Riskier patterns of drinking and other health-risk behaviors are associated with an increased preference for hard liquor and beer. Improved surveillance of alcoholic beverage preferences among youth will enable a better understanding of the factors related to youth drinking, allowing the development of more effective interventions. (Am J Prev Med 2011;40(4):419-426) (C) 2011 American Journal of Preventive Medicine C1 [Siegel, Michael B.] Boston Univ, Sch Publ Hlth, Dept Community Hlth Sci, Boston, MA 02118 USA. [Naimi, Timothy S.] Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02118 USA. [Cremeens, Jennifer L.] E Carolina Univ, Dept Hlth Educ & Promot, Coll Hlth & Human Performance, Greenville, NC USA. [Nelson, David E.] NCI, NIH, Rockville, MD USA. RP Siegel, MB (reprint author), Boston Univ, Sch Publ Hlth, Dept Community Hlth Sci, 801 Massachusetts Ave,3rd Floor, Boston, MA 02118 USA. EM mbsiegel@bu.edu NR 31 TC 30 Z9 30 U1 1 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD APR PY 2011 VL 40 IS 4 BP 419 EP 426 DI 10.1016/j.amepre.2010.12.011 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 734FN UT WOS:000288319700004 PM 21406275 ER PT J AU Chavez, PR Nelson, DE Naimi, TS Brewer, RD AF Chavez, Pollyanna R. Nelson, David E. Naimi, Timothy S. Brewer, Robert D. TI Impact of a New Gender-Specific Definition for Binge Drinking on Prevalence Estimates for Women SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID EXCESSIVE ALCOHOL-CONSUMPTION; HIGH-SCHOOL-STUDENTS; ADULTS; STATES; HARMS AB Background: Binge drinking accounts for more than half of the 79,000 deaths due to excessive drinking in the U.S. each year. In 2006, the Behavioral Risk Factor Surveillance System (BRFSS) lowered the threshold for defining binge drinking among women from >= 5 drinks to >= 4 drinks per occasion, in accordance with national recommendations. Purpose: To assess changes in binge-drinking prevalence among women. Methods: The relative and absolute change in binge drinking among U.S. adult women was assessed using pooled BRFSS data from the 2 years before (2004-2005) and after (2006-2007) the implementation of the new gender-specific definition. Analyses were conducted in 2008-2009. Results: Binge-drinking prevalence among women increased 2.6 percentage points (from 7.3% in 2004-2005 to 9.9% in 2006-2007), a 35.6% relative increase. The percentage of women who reported consuming exactly 4 drinks in 2006 (3.6%) was similar to the increase in the prevalence of binge drinking among women that was observed from 2005 to 2006 (absolute change=2.9 percentage points). Conclusions: The new gender-specific definition of binge drinking significantly increased the identification of women drinking at dangerous levels. The change in prevalence among women was primarily due to the change in the definition and not to actual changes in drinking behavior. The new gender-specific definition of binge drinking can increase the usefulness of this measure for public health surveillance and support the planning and implementation of effective prevention strategies (e.g., increasing alcohol excise taxes). (Am J Prev Med 2011;40(4):468-471) Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine C1 [Nelson, David E.] NCI, Canc Prevent Fellowship Program, Ctr Canc Training, NIH, Bethesda, MD 20892 USA. [Chavez, Pollyanna R.; Brewer, Robert D.] CDC, Alcohol Program, Emerging Invest & Analyt Methods Branch, Div Adult & Community Hlth,Natl Ctr Chron Dis Pre, Atlanta, GA 30333 USA. [Naimi, Timothy S.] Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02118 USA. RP Nelson, DE (reprint author), NCI, Canc Prevent Fellowship Program, Ctr Canc Training, NIH, 6120 Execut Blvd,EPS Bldg,Suite 150E, Bethesda, MD 20892 USA. EM nelsonde@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 19 TC 22 Z9 23 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD APR PY 2011 VL 40 IS 4 BP 468 EP 471 DI 10.1016/j.amepre.2010.12.008 PG 4 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 734FN UT WOS:000288319700011 PM 21406282 ER PT J AU Khoury, MJ Bowen, MS Burke, W Coates, RJ Dowling, NF Evans, JP Reyes, M St Pierre, J AF Khoury, Muin J. Bowen, Michael S. Burke, Wylie Coates, Ralph J. Dowling, Nicole F. Evans, James P. Reyes, Michele St Pierre, Jeannette TI Current Priorities for Public Health Practice in Addressing the Role of Human Genomics in Improving Population Health SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID GENETIC TESTING STRATEGIES; EGAPP WORKING GROUP; DISEASE PREVENTION; FAMILY-HISTORY; UNITED-STATES; COLORECTAL-CANCER; LYNCH SYNDROME; MEDICINE; HYPERCHOLESTEROLEMIA; RECOMMENDATIONS AB In spite of accelerating human genome discoveries in a wide variety of diseases of public health significance, the promise of personalized health care and disease prevention based on genomics has lagged behind. In a time of limited resources, public health agencies must continue to focus on implementing programs that can improve health and prevent disease now. Nevertheless, public health has an important and assertive leadership role in addressing the promise and pitfalls of human genomics for population health. Such efforts are needed not only to implement what is known in genomics to improve health but also to reduce potential harm and create the infrastructure needed to derive health benefits in the future. (Am J Prev Med 2011;40(4):486-493) (C) 2011 Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine. C1 [Khoury, Muin J.; Bowen, Michael S.; Coates, Ralph J.; Dowling, Nicole F.; Reyes, Michele; St Pierre, Jeannette] CDC, Off Publ Hlth Genom, Atlanta, GA 30333 USA. [Khoury, Muin J.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Burke, Wylie] Univ Washington, Dept Bioeth & Humanities, Seattle, WA 98195 USA. [Evans, James P.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. RP Khoury, MJ (reprint author), Ctr Dis Control & Prevent, Off Publ Hlth Genom, 1600 Clifton Rd, Atlanta, GA 30333 USA. EM muk1@cdc.gov NR 59 TC 30 Z9 31 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD APR PY 2011 VL 40 IS 4 BP 486 EP 493 DI 10.1016/j.amepre.2010.12.009 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 734FN UT WOS:000288319700014 PM 21406285 ER PT J AU Rahbari, R Mathur, A Kitano, M Guerrero, M Shen, WT Duh, QY Clark, OH Kebebew, E AF Rahbari, Reza Mathur, Aarti Kitano, Mio Guerrero, Marlon Shen, Wen T. Duh, Quan-Yang Clark, Orlo H. Kebebew, Electron TI Prospective Randomized Trial of Ligasure Versus Harmonic Hemostasis Technique in Thyroidectomy SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID SCALPEL; SURGERY; SYSTEM AB Two surgical devices have become popular in thyroid surgery: a bipolar energy sealing system (B) and ultrasonic coagulation (UC). Retrospective and prospective studies have demonstrated that the use of these surgical devices for thyroidectomy compared with conventional thyroidectomy (clamp-and-tie) techniques reduces operative time and cost. We conducted a prospective randomized clinical trial to determine if there is any difference in operative time and cost between B and UC. A single-blinded prospective randomized controlled trial was conducted at a tertiary referral center. A total of 90 patients who required a thyroidectomy for thyroid cancer, thyroid nodules, or hyperthyroidism were randomized to either B or UC during thyroidectomy. The operative time and cost of thyroidectomy were compared between the two groups. There was no statistically significant difference in patient age, gender, body mass index, indication for thyroidectomy and thyroid gland weight between the two groups. There was no statistically significant difference in operating room cost or total cost for thyroidectomy between the B and UC groups. There was also no statistically significant difference in the operative time between the B and UC groups (187.6 vs. 184.2 min, P = 0.48) or in postoperative complication rates. The only statistically significant difference in total cost was between surgeons independent of the device used (P < 0.01). In thyroid surgery, total cost and operative time were similar between the two surgical devices used. C1 [Rahbari, Reza; Mathur, Aarti; Kitano, Mio; Kebebew, Electron] NCI, Endocrine Oncol Sect, Surg Branch, Bethesda, MD 20892 USA. [Guerrero, Marlon] Univ Arizona, Dept Surg, Tucson, AZ USA. [Shen, Wen T.; Duh, Quan-Yang; Clark, Orlo H.] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. RP Kebebew, E (reprint author), NCI, Endocrine Oncol Sect, Surg Branch, Bethesda, MD 20892 USA. EM kebebewe@mail.nih.gov FU Covidien FX This study was sponsored by Covidien. NR 14 TC 25 Z9 25 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD APR PY 2011 VL 18 IS 4 BP 1023 EP 1027 DI 10.1245/s10434-010-1251-5 PG 5 WC Oncology; Surgery SC Oncology; Surgery GA 732TW UT WOS:000288213600020 PM 21072688 ER PT J AU Rahbari, R Holloway, AK He, M Khanafshar, E Clark, OH Kebebew, E AF Rahbari, Reza Holloway, Alisha K. He, Mei Khanafshar, Elham Clark, Orlo H. Kebebew, Electron TI Identification of Differentially Expressed MicroRNA in Parathyroid Tumors SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID CDNA MICROARRAY DATA; CARCINOMA; GENE; PARAFIBROMIN; NORMALIZATION; PHENOTYPE; DIAGNOSIS; DISEASE; CANCER; HRPT2 AB The molecular factors that control parathyroid tumorigenesis are poorly understood. In the absence of local invasion or metastasis, distinguishing benign from malignant parathyroid neoplasm is difficult on histologic examination. We studied the microRNA (miRNA) profile in normal, hyperplastic, and benign and malignant parathyroid tumors to better understand the molecular factors that may play a role in parathyroid tumorigenesis and that may serve as diagnostic markers for parathyroid carcinoma. miRNA arrays containing 825 human microRNAs with four duplicate probes per miRNA were used to profile parathyroid tumor (12 adenomas, 9 carcinomas, and 15 hyperplastic) samples normalized to four reference normal parathyroid glands. Differentially expressed miRNA were validated by real-time quantitative TaqMan polymerase chain reaction (PCR). One hundred fifty-six miRNAs in parathyroid hyperplasia, 277 microRNAs in parathyroid adenoma, and 167 microRNAs in parathyroid carcinomas were significantly dysregulated as compared with normal parathyroid glands [false discovery rate (FDR) < 0.05]. By supervised clustering analysis, all parathyroid carcinomas clustered together. Three miRNAs (miR-26b, miR-30b, and miR-126*) were significantly dysregulated between parathyroid carcinoma and parathyroid adenoma. Receiver-operating characteristic curve analysis showed mir-126* was the best diagnostic marker, with area under the curve of 0.776. Most miRNAs are downregulated in parathyroid carcinoma, while in parathyroid hyperplasia most miRNAs are upregulated. miRNA profiling shows distinct differentially expressed miRNAs by tumor type which may serve as helpful adjunct to distinguish parathyroid adenoma from carcinoma. C1 [Rahbari, Reza; He, Mei; Kebebew, Electron] NCI, Endocrine Oncol Sect, Surg Branch, Bethesda, MD 20892 USA. [Holloway, Alisha K.] Univ Calif San Francisco, Gladstone Inst, San Francisco, CA 94143 USA. [Khanafshar, Elham] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA. [Clark, Orlo H.] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. RP Rahbari, R (reprint author), NCI, Endocrine Oncol Sect, Surg Branch, Bethesda, MD 20892 USA. EM kebebewe@mail.nih.gov RI Holloway, Alisha/H-9574-2013 OI Holloway, Alisha/0000-0001-9810-389X FU UCSF Comprehensive Cancer Center; American Cancer Society; NIH, National Cancer Institute, Center for Cancer Research FX This work was supported in part by grants from the UCSF Comprehensive Cancer Center, American Cancer Society, and the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 33 TC 2 Z9 2 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD APR PY 2011 VL 18 IS 4 BP 1158 EP 1165 DI 10.1245/s10434-010-1359-7 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA 732TW UT WOS:000288213600039 ER PT J AU Gleichmann, M Mattson, MP AF Gleichmann, Marc Mattson, Mark P. TI Neuronal Calcium Homeostasis and Dysregulation SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Review ID MITOCHONDRIAL PERMEABILITY TRANSITION; ALZHEIMERS-DISEASE; OXIDATIVE STRESS; CELL-DEATH; ENDOPLASMIC-RETICULUM; LIVER-MITOCHONDRIA; CYCLOPHILIN-D; ENERGY-METABOLISM; CRAC CHANNEL; MYOCARDIAL-INFARCTION AB The calcium ion (Ca2+) is the main second messenger that helps to transmit depolarization status and synaptic activity to the biochemical machinery of a neuron. These features make Ca2+ regulation a critical process in neurons, which have developed extensive and intricate Ca2+ signaling pathways. High intensity Ca2+ signaling necessitates high ATP consumption to restore basal (low) intracellular Ca2+ levels after Ca2+ influx through plasma membrane receptor and voltage-dependent ion channels. Ca2+ influx may also lead to increased generation of mitochondrial reactive oxygen species (ROS). Impaired abilities of neurons to maintain cellular energy levels and to suppress ROS may impact Ca2+ signaling during aging and in neurodegenerative disease processes. This review focuses on mitochondrial and endoplasmic reticulum Ca2+ homeostasis and how they relate to synaptic Ca2+ signaling processes, neuronal energy metabolism, and ROS generation. Also, the contribution of altered Ca2+ signaling to neurodegeneration during aging will be considered. Advances in understanding the molecular regulation of Ca2+ homeostasis and how it is perturbed in neurological disorders may lead to therapeutic strategies that modulate neuronal Ca2+ signaling to enhance function and counteract disease processes. Antioxid. Redox Signal. 14, 1261-1273. C1 [Gleichmann, Marc; Mattson, Mark P.] NIA, Neurosci Lab, Baltimore, MD 21224 USA. RP Gleichmann, M (reprint author), Merck Serono SA, GCDU Neurodegenerat Dis, Chemin Mines 9, CH-1202 Geneva, Switzerland. EM marc.gleichmann@gmail.com RI Mattson, Mark/F-6038-2012 FU NIH, National Institute on Aging FX This research was entirely supported by the Intramural Research Program NIH, National Institute on Aging. We thank K.C. Alexander for help with the figures. NR 102 TC 76 Z9 77 U1 0 U2 8 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD APR PY 2011 VL 14 IS 7 BP 1261 EP 1273 DI 10.1089/ars.2010.3386 PG 13 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 732BN UT WOS:000288157300008 PM 20626318 ER PT J AU Baek, JI Park, HJ Park, K Choi, SJ Lee, KY Yi, JH Friedman, TB Drayna, D Shin, KS Kim, UK AF Baek, Jeong-In Park, Hong-Joon Park, Kyungjoon Choi, Su-Jin Lee, Kyu-Yup Yi, Jee Hyun Friedman, Thomas B. Drayna, Dennis Shin, Ki Soon Kim, Un-Kyung TI Pathogenic effects of a novel mutation (c.664_681del) in KCNQ4 channels associated with auditory pathology SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE LA English DT Article DE Hearing loss; KCNQ4; K(+) channel; Mutation; Dominant negative effect ID LONG-QT SYNDROME; SHAKER POTASSIUM CHANNELS; SENSORINEURAL HEARING-LOSS; DOMINANT DEAFNESS; K+ CHANNEL; LINKAGE ANALYSIS; VOLTAGE SENSOR; S4-S5 LINKER; PORE-REGION; HOT-SPOT AB Hearing loss is a common communication disorder caused by various environmental and genetic factors. Hereditary hearing loss is very heterogeneous, and most of such cases involve sensorineural defects in the auditory pathway. There are currently 57 known autosomal dominant non-syndromic hearing loss (DFNA) loci, and the causative genes have been identified at 22 of these loci. In the present study, we performed a genome-wide linkage analysis in a Korean family segregating autosomal dominant hearing loss. We observed linkage on chromosome 1p34, and at this locus, we detected a novel mutation consisting of an 18 nucleotide deletion in exon 4 of the KCNQ4 gene, which encodes a voltage-gated potassium channel. We carried out a functional in vitro study to analyze the effects of this mutation (c.664_681del) along with two previously described KCNQ4 mutations, p.W276S and p.G285C. Although the c.664_681del mutation is located in the intercellular loop and the two previously described mutations, p.W276S and p.G285C, are located in the pore region, all mutants inhibit normal channel function by a dominant negative effect. Our analysis indicates that the intercellular loop is as significant as the pore region as a potential site of pathogenic effects on KCNQ4 channel function. (C) 2010 Elsevier B.V. All rights reserved. C1 [Baek, Jeong-In; Choi, Su-Jin; Kim, Un-Kyung] Kyungpook Natl Univ, Dept Biol, Coll Nat Sci, Taegu 702701, South Korea. [Park, Hong-Joon] Soree Ear Clin, Seoul, South Korea. [Park, Kyungjoon; Yi, Jee Hyun; Shin, Ki Soon] Kyung Hee Univ, Dept Biol, Dept Life & Nanopharmaceut Sci, Seoul, South Korea. [Lee, Kyu-Yup] Kyungpook Natl Univ, Dept Otorhinolaryngol Head & Neck Surg, Coll Med, Taegu 702701, South Korea. [Friedman, Thomas B.; Drayna, Dennis] Natl Inst Deafness & Other Commun Disorders, Mol Genet Lab, NIH, Rockville, MD 20850 USA. RP Kim, UK (reprint author), Kyungpook Natl Univ, Dept Biol, Coll Nat Sci, Taegu 702701, South Korea. EM kimuk@knu.ac.kr FU Korea government (MEST) [R01-2008-000-10431-0]; Ministry for Health, Welfare and Family Affairs, Republic of Korea [A080588] FX We are grateful to the family for their collaboration in this study. This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MEST) (R01-2008-000-10431-0), a grant of the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare and Family Affairs, Republic of Korea, A080588 (UKK). NR 35 TC 9 Z9 10 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4439 J9 BBA-MOL BASIS DIS JI Biochim. Biophys. Acta-Mol. Basis Dis. PD APR PY 2011 VL 1812 IS 4 BP 536 EP 543 DI 10.1016/j.bbadis.2010.09.001 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 733YX UT WOS:000288301500014 PM 20832469 ER PT J AU Mascia, P Pistis, M Justinova, Z Panlilio, LV Luchicchi, A Lecca, S Scherma, M Fratta, W Fadda, P Barnes, C Redhi, GH Yasar, S Le Foll, B Tanda, G Piomelli, D Goldberg, SR AF Mascia, Paola Pistis, Marco Justinova, Zuzana Panlilio, Leigh V. Luchicchi, Antonio Lecca, Salvatore Scherma, Maria Fratta, Walter Fadda, Paola Barnes, Chanel Redhi, Godfrey H. Yasar, Sevil Le Foll, Bernard Tanda, Gianluigi Piomelli, Daniele Goldberg, Steven R. TI Blockade of Nicotine Reward and Reinstatement by Activation of Alpha-Type Peroxisome Proliferator-Activated Receptors SO BIOLOGICAL PSYCHIATRY LA English DT Article DE FAAH; nicotine; OEA; PEA; PPAR-alpha; reinstatement; reward ID VENTRAL TEGMENTAL AREA; CONDITIONED PLACE PREFERENCES; CENTRAL-NERVOUS-SYSTEM; DISCRIMINATIVE-STIMULUS; DOPAMINE NEURONS; ACETYLCHOLINE-RECEPTORS; NUCLEUS-ACCUMBENS; ESTER URB597; PPAR-ALPHA; RATS AB Background: Recent findings indicate that inhibitors of fatty acid amide hydrolase (FAAH) counteract the rewarding effects of nicotine in rats. Inhibition of FAAH increases levels of several endogenous substances in the brain, including the endocannabinoid anandamide and the noncannabinoid fatty acid ethanolamides oleoylethanolamide (OEA) and palmitoylethanolamide, which are ligands for alpha-type peroxisome proliferator-activated nuclear receptors (PPAR-alpha). Here, we evaluated whether directly acting PPAR-alpha agonists can modulate reward-related effects of nicotine. Methods: We combined behavioral, neurochemical, and electrophysiological approaches to evaluate effects of the PPAR-alpha agonists [[4-Chloro-6-[(2,3-dimethylphenyl)amino]-2-pyrimidinyl]thio] acetic acid (WY14643) and methyl oleoylethanolamide (methOEA; a long-lasting form of OEA) on 1) nicotine self-administration in rats and squirrel monkeys; 2) reinstatement of nicotine-seeking behavior in rats and monkeys; 3) nicotine discrimination in rats; 4) nicotine-induced electrophysiological activity of ventral tegmental area dopamine neurons in anesthetized rats; and 5) nicotine-induced elevation of dopamine levels in the nucleus accumbens shell of freely moving rats. Results: The PPAR-alpha agonists dose-dependently decreased nicotine self-administration and nicotine-induced reinstatement in rats and monkeys but did not alter food- or cocaine-reinforced operant behavior or the interoceptive effects of nicotine. The PPAR-alpha agonists also dose-dependently decreased nicotine-induced excitation of dopamine neurons in the ventral tegmental area and nicotine-induced elevations of dopamine levels in the nucleus accumbens shell of rats. The ability of WY14643 and methOEA to counteract the behavioral, electrophysiological, and neurochemical effects of nicotine was reversed by the PPAR-alpha antagonist 1-[(4-Chlorophenyl)methyl]-3-[(1,1-dimethylethyl)thio]-a,a-dimethyl-5-(1-methylethyl)-1H-Indole-2-propanoic acid (MK886). Conclusions: These findings indicate that PPAR-alpha might provide a valuable new target for antismoking medications. C1 [Goldberg, Steven R.] NIDA, Biomed Res Ctr, Preclin Pharmacol Sect, Behav Neurosci Res Branch,NIH,Dept Hlth & Human S, Baltimore, MD 21224 USA. [Tanda, Gianluigi] NIDA, Psychobiol Sect, Medicat Discovery Res Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. [Yasar, Sevil] Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, Baltimore, MD 21218 USA. [Justinova, Zuzana] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. [Pistis, Marco; Luchicchi, Antonio; Lecca, Salvatore; Scherma, Maria; Fratta, Walter; Fadda, Paola] Univ Cagliari, Dept Neurosci, Monserrato, Italy. [Le Foll, Bernard] Univ Toronto, Translat Addict Res Lab, Ctr Addict & Mental Hlth, Toronto, ON, Canada. [Piomelli, Daniele] Univ Calif Irvine, Dept Pharmacol, Irvine, CA 92717 USA. RP Goldberg, SR (reprint author), NIDA, Biomed Res Ctr, Preclin Pharmacol Sect, Behav Neurosci Res Branch,NIH,Dept Hlth & Human S, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM sgoldber@intra.nida.nih.gov RI Tanda, Gianluigi/B-3318-2009; Justinova, Zuzana/A-9109-2011; Pistis, Marco/A-3773-2013; Le Foll, Bernard/K-2952-2014; OI Tanda, Gianluigi/0000-0001-9526-9878; Justinova, Zuzana/0000-0001-5793-7484; Pistis, Marco/0000-0002-4622-3205; Le Foll, Bernard/0000-0002-6406-4973; Luchicchi, Antonio/0000-0002-0189-4347; FADDA, PAOLA/0000-0002-0642-6710 FU National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services; Italian Ministry of University and Scientific Research; University of Cagliari Center of Excellence on Neurobiology of Dependence; Department of Psychiatry, University of Maryland School of Medicine; Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine; Department of Pharmacology, University of California, Irvine FX This study was supported in part by the Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services; by the Italian Ministry of University and Scientific Research and the University of Cagliari Center of Excellence on Neurobiology of Dependence; by the Department of Psychiatry, University of Maryland School of Medicine; by the Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine; and by the Department of Pharmacology, University of California, Irvine. NR 43 TC 49 Z9 50 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 2011 VL 69 IS 7 BP 633 EP 641 DI 10.1016/j.biopsych.2010.07.009 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 733FI UT WOS:000288248100006 PM 20801430 ER PT J AU Stopponi, S Somaini, L Cippitelli, A Cannella, N Braconi, S Kallupi, M Ruggeri, B Heilig, M Demopulos, G Gaitanaris, G Massi, M Ciccocioppo, R AF Stopponi, Serena Somaini, Lorenzo Cippitelli, Andrea Cannella, Nazzareno Braconi, Simone Kallupi, Marsida Ruggeri, Barbara Heilig, Markus Demopulos, Gregory Gaitanaris, George Massi, Maurizio Ciccocioppo, Roberto TI Activation of Nuclear PPAR gamma Receptors by the Antidiabetic Agent Pioglitazone Suppresses Alcohol Drinking and Relapse to Alcohol Seeking SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Addiction; alcohol drinking; pioglitazone; PPAR gamma receptors; relapse; thiazolidinediones ID ETHANOL WITHDRAWAL; OPIOID WITHDRAWAL; NEUROPATHIC PAIN; INDUCED ANXIETY; BINDING-SITES; DB/DB MICE; REINSTATEMENT; RATS; DOPAMINE; BEHAVIOR AB Background: Pioglitazone and rosiglitazone belong to the class of thiazolidinediones (TZDs). They were first developed as antioxidants and then approved for the clinical treatment of insulin resistance and Type 2 diabetes. TZDs bind with high affinity and activate peroxisome proliferator-activated receptor-gamma (PPAR gamma) receptors, which in the brain are expressed both in neurons and in glia. Methods: We evaluated the effect of PPAR gamma activation by TZDs on alcohol drinking, relapse-like behavior, and withdrawal in the rat. We also tested the effect of TZDs on alcohol and saccharin self-administration. Results: We showed that activation of PPAR gamma receptors by pioglitazone (0, 10, and 30 mg/kg) and rosiglitazone (0, 10 and 30 mg/kg) given orally selectively reduced alcohol drinking. The effect was blocked by pretreatment with the selective PPAR gamma antagonist GW9662 (5 mu g/rat) given into the lateral cerebroventricle, suggesting that this TZD's effect is mediated by PPAR gamma receptors in the central nervous system. Pioglitazone abolished reinstatement of alcohol seeking, a relapse-like behavior, induced by yohimbine, a pharmacologic stressor, but did not affect cue-induced relapse. In the self-administration experiments, pioglitazone reduced lever pressing for alcohol but not for saccharin. Finally, pioglitazone prevented the expression of somatic signs of alcohol withdrawal. Conclusions: These findings provide new information about the role of brain PPAR gamma receptors and identify pioglitazone as candidate treatments for alcoholism and possibly other addictions. C1 [Stopponi, Serena; Cippitelli, Andrea; Cannella, Nazzareno; Braconi, Simone; Kallupi, Marsida; Ruggeri, Barbara; Massi, Maurizio; Ciccocioppo, Roberto] Univ Camerino, Sch Pharm, Pharmacol Unit, I-62032 Camerino, Italy. [Somaini, Lorenzo] Addict Treatment Ctr, Hlth Local Unit, Biella, Italy. [Cippitelli, Andrea; Heilig, Markus] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA. [Demopulos, Gregory; Gaitanaris, George] Omeros Corp, Seattle, WA USA. RP Ciccocioppo, R (reprint author), Univ Camerino, Sch Pharm, Pharmacol Unit, I-62032 Camerino, Italy. EM roberto.ciccocioppo@unicam.it RI Ruggeri, Barbara/A-9787-2013; OI Ruggeri, Barbara/0000-0002-6231-8829; Heilig, Markus/0000-0003-2706-2482 FU University of Camerino FX This study was supported by the University of Camerino (Grant FAR to RC). We thank Alfredo Fiorelli, Rina Righi, and Marino Cucculelli for expert technical assistance. NR 67 TC 45 Z9 45 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 2011 VL 69 IS 7 BP 642 EP 649 DI 10.1016/j.biopsych.2010.12.010 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 733FI UT WOS:000288248100007 PM 21276964 ER PT J AU Bedi, G Preston, KL Epstein, DH Heishman, SJ Marrone, GF Shaham, Y de Wit, H AF Bedi, Gillinder Preston, Kenzie L. Epstein, David H. Heishman, Stephen J. Marrone, Gina F. Shaham, Yavin de Wit, Harriet TI Incubation of Cue-Induced Cigarette Craving During Abstinence in Human Smokers SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Addiction; cigarette smoking; cue-induced craving; incubation of craving; relapse ID DRUG SEEKING; RELAPSE; REACTIVITY; WITHDRAWAL; DURATION; SMOKING; HEROIN AB Background: Abstinent drug users remain at risk for relapse long after withdrawal subsides. Animal studies indicate that responses to drug-related cues not only persist but increase with abstinence, a phenomenon termed "incubation of drug craving." It is unknown whether cue-induced craving increases, decreases, or remains constant with abstinence in humans. We investigated effects of abstinence on cue-induced craving in cigarette smokers. Methods: Eighty-six non-treatment-seeking, adult smokers (>= 10 cigarettes daily) were paid to abstain for 7 (Group 1), 14 (Group 2), or 35 (Groups 3 and 4) days. Abstinence was verified daily. Groups 1, 2, and 3 underwent a single cue session on the final abstinence day (7, 14, or 35). Group 4 viewed cues on Days 7, 14, and 35. Results: Between and within groups, smoking-cue-induced craving increased with abstinence on some measures. Cue-induced craving was greater in Group 3 (35-day) compared with Group 1 (7-day). Within Group 4, cue-induced craving was greater at 35 than 14 days. Cue-induced craving did not decrease with abstinence on any measure. Conclusions: We present initial evidence of incubation of cue-induced craving in humans. The observation that cue-induced craving increases with abstinence, even as "background" craving and withdrawal symptoms subside, might have treatment implications. C1 [Bedi, Gillinder] Univ Chicago, Dept Psychiat & Behav Neurosci, Human Behav Pharmacol Lab, Chicago, IL 60637 USA. [Preston, Kenzie L.; Epstein, David H.; Heishman, Stephen J.; Marrone, Gina F.; Shaham, Yavin] NIDA, Intramural Res Program, Baltimore, MD USA. [Bedi, Gillinder] Columbia Univ, Coll Phys & Surg, Div Subst Abuse, New York State Psychiat Inst, New York, NY USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. RP Bedi, G (reprint author), Univ Chicago, Dept Psychiat & Behav Neurosci, Human Behav Pharmacol Lab, 5841 S Maryland Ave,MC 3077, Chicago, IL 60637 USA. EM GB2326@columbia.edu RI Preston, Kenzie/J-5830-2013; shaham, yavin/G-1306-2014; OI Preston, Kenzie/0000-0003-0603-2479; de Wit, Harriet/0000-0002-7211-8994 FU National Institute on Drug Abuse [R21DA020773] FX This work was supported by the National Institute on Drug Abuse (R21DA020773) and National Institute on Drug Abuse Intramural Research Program. We thank Patricia Kreigel, Jamie Golden, Erin Prater, Alex Gomes, and Rebecca Evans for technical assistance and Drs. Royce Lee and Karran Phillips for medical support. We offer many thanks to the participants. NR 20 TC 60 Z9 61 U1 1 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 2011 VL 69 IS 7 BP 708 EP 711 DI 10.1016/j.biopsych.2010.07.014 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 733FI UT WOS:000288248100016 PM 20817135 ER PT J AU Lamont, RF Sobel, JD Akins, RA Hassan, SS Chaiworapongsa, T Kusanovic, JP Romero, R AF Lamont, R. F. Sobel, J. D. Akins, R. A. Hassan, S. S. Chaiworapongsa, T. Kusanovic, J. P. Romero, R. TI The vaginal microbiome: new information about genital tract flora using molecular based techniques SO BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY LA English DT Review DE Bacteria; colonisation; culture; microbiome; molecular; vagina ID POLYMERASE-CHAIN-REACTION; 16S RIBOSOMAL-RNA; CULTIVATION-INDEPENDENT METHODS; HYDROGEN-PEROXIDE PRODUCTION; SEQUENCE-BASED METHODS; SIMPLEX-VIRUS TYPE-2; CHLAMYDIA-TRACHOMATIS INFECTION; DIAGNOSING BACTERIAL VAGINOSIS; INFLAMMATORY RESPONSE SYNDROME; LACTOBACILLUS-RHAMNOSUS GR-1 AB Vaginal microbiome studies provide information that may change the way we define vaginal flora. Normal flora appears dominated by one or two species of Lactobacillus. Significant numbers of healthy women lack appreciable numbers of vaginal lactobacilli. Bacterial vaginosis (BV) is not a single entity, but instead consists of different bacterial communities or profiles of greater microbial diversity than is evident from cultivation-dependent studies. BV should be considered a syndrome of variable composition that results in different symptoms, phenotypical outcomes, and responses to different antibiotic regimens. This information may help to elucidate the link between BV and infection-related adverse outcomes of pregnancy. C1 [Lamont, R. F.; Hassan, S. S.; Chaiworapongsa, T.; Kusanovic, J. P.; Romero, R.] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD 20892 USA. [Lamont, R. F.; Hassan, S. S.; Chaiworapongsa, T.; Kusanovic, J. P.; Romero, R.] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. [Sobel, J. D.] Wayne State Univ, Hutzel Hosp, Dept Infect Dis, Detroit, MI USA. [Lamont, R. F.; Hassan, S. S.; Chaiworapongsa, T.; Kusanovic, J. P.] Wayne State Univ, Dept Obstet & Gynecol, Hutzel Hosp, Detroit, MI USA. [Akins, R. A.] Wayne State Univ, Sch Med, Dept Biochem & Mol Biol, Detroit, MI USA. [Romero, R.] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. RP Lamont, RF (reprint author), NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD 20892 USA. EM rlamont@med.wayne.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS FX Supported (in part) by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 216 TC 123 Z9 147 U1 1 U2 35 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1470-0328 EI 1471-0528 J9 BJOG-INT J OBSTET GY JI BJOG PD APR PY 2011 VL 118 IS 5 BP 533 EP 549 DI 10.1111/j.1471-0528.2010.02840.x PG 17 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 733GQ UT WOS:000288251600003 PM 21251190 ER PT J AU Kmieciak, M Worschech, A Nikizad, H Gowda, M Habibi, M Depcrynski, A Wang, E Godder, K Holt, SE Marincola, FM Manjili, MH AF Kmieciak, Maciej Worschech, Andrea Nikizad, Hooman Gowda, Madhu Habibi, Mehran Depcrynski, Amy Wang, Ena Godder, Kamar Holt, Shawn E. Marincola, Francesco M. Manjili, Masoud H. TI CD4+T cells inhibit the neu-specific CD8+T-cell exhaustion during the priming phase of immune responses against breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; HER-2/neu; Helpless CD8+T cells; CD4+helper T cells; Memory T cells ID CD8(+) T-CELLS; TELOMERE LENGTH; EXPRESSION PATTERNS; RNA AMPLIFICATION; MELANOMA; MEMORY; LYMPHOCYTES; PERSISTENCE; INFECTION; LINES AB Studies conducted in animal model of infectious diseases or H-Y antigen model suggest a crucial role for CD4+ T cells in providing help for CD8+ T-cell memory responses. This concept suggests that inclusion of T helper epitopes in vaccine formulation will result in improved CD8+ T-cell responses. Although this concept has been applied to cancer vaccine design, the role of CD4+ T cells in the memory differentiation of CD8+ T cells and retention of their anti-tumor function have never been tested in breast cancer model. Using the FVB mouse model of neu-positive breast carcinoma we report for the first time that helpless T cells showed cytostatic or tumor inhibitory effects during primary tumor challenge whereas, helped T cells showed cytotoxic effects and resulted in complete tumor rejection. Such differential effects, in vivo, were associated with higher frequency of CD8+PD-L1+ and CD8+PD-1+ T cells in animals harboring helpless T cells as well as higher titer of IL-2 in the sera of animals harboring helped T cells. However, depletion of CD4+ T cells did not alter the ability of neu-specific CD8+ T cells to differentiate into memory cells and to retain their effector function against the tumor during recall challenge. These results suggest the inhibitory role of CD4+ T cells on CD8+ T-cell exhaustion without substantial effects on the differentiation of memory T cells during priming phase of the immune responses against breast cancer. C1 [Kmieciak, Maciej; Nikizad, Hooman; Manjili, Masoud H.] Virginia Commonwealth Univ, Dept Microbiol & Immunol, Massey Canc Ctr, Richmond, VA 23298 USA. [Worschech, Andrea; Wang, Ena; Marincola, Francesco M.] NIH, IDIS, Dept Transfus Med, Bethesda, MD 20892 USA. [Worschech, Andrea; Wang, Ena; Marincola, Francesco M.] NIH, Ctr Human Immunol, Bethesda, MD 20892 USA. [Worschech, Andrea] Univ Wurzburg, Inst Biochem, D-97074 Wurzburg, Germany. [Worschech, Andrea] Genelux Corp, Res & Dev, San Diego, CA USA. [Gowda, Madhu; Godder, Kamar] Virginia Commonwealth Univ, Dept Pediat, Massey Canc Ctr, Richmond, VA 23298 USA. [Habibi, Mehran] Johns Hopkins Univ, Sch Med, Baltimore, MD 21224 USA. [Depcrynski, Amy; Holt, Shawn E.] Virginia Commonwealth Univ, Dept Pathol, Massey Canc Ctr, Richmond, VA 23298 USA. RP Manjili, MH (reprint author), Virginia Commonwealth Univ, Dept Microbiol & Immunol, Massey Canc Ctr, Box 980035, Richmond, VA 23298 USA. EM mmanjili@vcu.edu RI Worschech, Andrea/I-3919-2012 OI Worschech, Andrea/0000-0002-4303-8653 FU NIH [R01 CA104757, P30CA16059]; VCU Massey Cancer Centre; Commonwealth Foundation for Cancer Research FX This work was supported by NIH R01 CA104757 Grant (M. H. Manjili) and flow cytometry shared resources facility supported in part by the NIH Grant P30CA16059. We thank Dr. William Lee of the U Penn for providing us with pEF2-dnIFN-gamma R alpha vector. We also thank Julie Farnsworth for her expertise in cell sorting and immense dedication to furthering the research at our institution. We gratefully acknowledge the support of VCU Massey Cancer Centre and the Commonwealth Foundation for Cancer Research. NR 28 TC 9 Z9 9 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD APR PY 2011 VL 126 IS 2 BP 385 EP 394 DI 10.1007/s10549-010-0942-8 PG 10 WC Oncology SC Oncology GA 733GK UT WOS:000288251000011 PM 20480224 ER PT J AU Lemery, SJ Hsieh, MM Smith, A Rao, S Khuu, HM Theresa, D Viano, JM Cook, L Goodwin, R Boss, C Calandra, G Geller, N Tisdale, J Childs, R AF Lemery, Steven J. Hsieh, Matthew M. Smith, Aleah Rao, Sheila Khuu, Hanh M. Theresa, Donohue Viano, Jennifer M. Cook, Lisa Goodwin, Rose Boss, Carol Calandra, Gary Geller, Nancy Tisdale, John Childs, Richard TI A pilot study evaluating the safety and CD34+ cell mobilizing activity of escalating doses of plerixafor in healthy volunteers SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE stem cell mobilization; homing; plerixafor; CD34; BMT; clinical research ID HEMATOPOIETIC PROGENITOR CELLS; PERIPHERAL-BLOOD; G-CSF; STEM-CELLS; RAPID MOBILIZATION; MULTIPLE-MYELOMA; CXCR4 ANTAGONIST; T-CELLS; AMD3100; TRANSPLANTATION AB P>This study evaluated the safety and CD34+ cell mobilizing activity of escalating doses of plerixafor in healthy volunteers. Three cohorts of six subjects received two different doses of plerixafor separated by at least 2 weeks to allow for adequate pharmacodynamic wash-out. The following dosing cohorts were evaluated: 0 center dot 24 and 0 center dot 32 mg/kg (Cohort 1); 0 center dot 32 and 0 center dot 40 mg/kg (Cohort 2); and 0 center dot 40 and 0 center dot 48 mg/kg (Cohort 3). Circulating CD34+ cells were measured 0, 2, 4, 6, 8, 10, 12, 14, 18 and 24 h after each dose. Blood colony-forming units were measured at baseline and 6 h after each dose. Common adverse events were diarrhoea, injection site erythema, perioral numbness, sinus tachycardia, headache, nausea, abdominal distention and injection site pain. No dose limiting toxicities occurred. When higher doses of plerixafor were administered, there was a trend towards higher peak CD34+ counts and CD34+ area under the curves, although these differences did not achieve statistical significance, perhaps due to intra-subject variability. Together, these data show that the higher doses of plerixafor evaluated in this study are reasonably safe and suggest that a larger study should be performed to definitively answer whether increased numbers of CD34+ cell are mobilized with higher doses of plerixafor. C1 [Childs, Richard] NHLBI, NIH, Hematol Branch, Bethesda, MD 20892 USA. [Hsieh, Matthew M.; Tisdale, John] NIDDK, NIH, Bethesda, MD USA. [Khuu, Hanh M.] NIH, DTM, Bethesda, MD 20892 USA. [Calandra, Gary] AnorMED, Langley, BC, Canada. RP Childs, R (reprint author), NHLBI, NIH, Hematol Branch, Room 3-5330,10-CRC, Bethesda, MD 20892 USA. EM childsr@nhlbi.nih.gov FU National Heart, Lung and Blood Institute; Clinical Center, National Institutes of Health FX This research was supported by the Intramural Research Programs of the National Heart, Lung and Blood Institute and the Clinical Center, National Institutes of Health. The authors would like to acknowledge Marjie Hard, PhD from Genzyme for conducting the pharmacokinetic analyses described in this manuscript. NR 22 TC 8 Z9 8 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD APR PY 2011 VL 153 IS 1 BP 66 EP 75 DI 10.1111/j.1365-2141.2010.08547.x PG 10 WC Hematology SC Hematology GA 733GH UT WOS:000288250700008 PM 21352197 ER PT J AU Ramaswamy, M Cruz, AC Cleland, SY Deng, M Price, S Rao, VK Siegel, RM AF Ramaswamy, M. Cruz, A. C. Cleland, S. Y. Deng, M. Price, S. Rao, V. K. Siegel, R. M. TI Specific elimination of effector memory CD4(+) T cells due to enhanced Fas signaling complex formation and association with lipid raft microdomains SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE Fas; death receptors; lipid raft microdomains; CD4 T cells; apoptosis ID AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME; SYSTEMIC-LUPUS-ERYTHEMATOSUS; LYMPHOCYTE APOPTOSIS; TNF-ALPHA; DEATH; ANTIGEN; BIM; DIFFERENTIATION; HOMEOSTASIS; ACTIVATION AB Elimination of autoreactive CD4(+) T cells through the death receptor Fas/CD95 is an important mechanism of immunological self-tolerance. Fas deficiency results in systemic autoimmunity, yet does not affect the kinetics of T-cell responses to acute antigen exposure or infection. Here we show that Fas and TCR-induced apoptosis are largely restricted to CD4(+) T cells with an effector memory phenotype (effector memory T cells (T-EM)), whereas central memory and activated naive CD4(+) T cells are relatively resistant to both. Sensitivity of T-EM to Fas-induced apoptosis depends on enrichment of Fas in lipid raft microdomains, and is linked to more efficient formation of the Fas death-inducing signaling complex. These results explain how Fas can cull T cells reactive against self-antigens without affecting acute immune responses. This work also identifies Fas-induced apoptosis as a possible immunotherapeutic strategy to eliminate T-EM linked to the pathogenesis of a number of autoimmune diseases. Cell Death and Differentiation (2011) 18, 712-720; doi:10.1038/cdd.2010.155; published online 17 December 2010 C1 [Ramaswamy, M.; Cruz, A. C.; Cleland, S. Y.; Deng, M.; Siegel, R. M.] NIAMS, Immunoregulat Sect, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. [Price, S.; Rao, V. K.] NIAID, ALPS Unit, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Siegel, RM (reprint author), NIAMS, Immunoregulat Sect, Autoimmun Branch, NIH, Bldg 10 Room,13C103, Bethesda, MD 20892 USA. EM siegelr@mail.nih.gov FU National Institute of Arthritis; Musculoskeletal and Skin Diseases of the National Institutes of Health. FX We would like to thank Jagan Muppidi for construction of the FasL-LZ vector, Mike Lenardo, John Ashwell and Josh Farber for critical reading of the paper, Andy Snow for providing Bim siRNA, Jim Simone and Jeff Lay for assistance in cell sorting. This research 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 39 TC 18 Z9 18 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD APR PY 2011 VL 18 IS 4 BP 712 EP 720 DI 10.1038/cdd.2010.155 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 734DY UT WOS:000288314800013 PM 21164519 ER PT J AU Wojciechowski, R AF Wojciechowski, R. TI Nature and nurture: the complex genetics of myopia and refractive error SO CLINICAL GENETICS LA English DT Review DE epidemiology; genetics; myopia; refractive errors ID HIGH-GRADE MYOPIA; BEAVER DAM EYE; HEPATOCYTE GROWTH-FACTOR; GENOME-WIDE SCAN; PIRENZEPINE OPHTHALMIC GEL; AUSTRALIAN SCHOOL-CHILDREN; JUVENILE-ONSET MYOPIA; NEAR-WORK ACTIVITY; VISUAL IMPAIRMENT; OCULAR REFRACTION AB The refractive errors, myopia and hyperopia, are optical defects of the visual system that can cause blurred vision. Uncorrected refractive errors are the most common causes of visual impairment worldwide. It is estimated that 2.5 billion people will be affected by myopia alone within the next decade. Experimental, epidemiological and clinical research has shown that refractive development is influenced by both environmental and genetic factors. Animal models have showed that eye growth and refractive maturation during infancy are tightly regulated by visually guided mechanisms. Observational data in human populations provide compelling evidence that environmental influences and individual behavioral factors play crucial roles in myopia susceptibility. Nevertheless, the majority of the variance of refractive error within populations is thought to be because of hereditary factors. Genetic linkage studies have mapped two dozen loci, while association studies have implicated more than 25 different genes in refractive variation. Many of these genes are involved in common biological pathways known to mediate extracellular matrix (ECM) composition and regulate connective tissue remodeling. Other associated genomic regions suggest novel mechanisms in the etiology of human myopia, such as mitochondrial-mediated cell death or photoreceptor-mediated visual signal transmission. Taken together, observational and experimental studies have revealed the complex nature of human refractive variation, which likely involves variants in several genes and functional pathways. Multiway interactions between genes and/or environmental factors may also be important in determining individual risks of myopia, and may help explain the complex pattern of refractive error in human populations. C1 NHGRI, Stat Genet Sect, Inherited Dis Branch, NIH, Baltimore, MD 21224 USA. RP Wojciechowski, R (reprint author), NHGRI, Stat Genet Sect, Inherited Dis Branch, NIH, 333 Cassell Dr,Suite 1200, Baltimore, MD 21224 USA. EM robwoj@mail.nih.gov OI Wojciechowski, Robert/0000-0002-9593-4652 FU National Human Genome Research Institute, National Institutes of Health FX This work was supported by intramural program of the National Human Genome Research Institute, National Institutes of Health. NR 204 TC 86 Z9 90 U1 13 U2 71 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD APR PY 2011 VL 79 IS 4 BP 301 EP 320 DI 10.1111/j.1399-0004.2010.01592.x PG 20 WC Genetics & Heredity SC Genetics & Heredity GA 730FJ UT WOS:000288018700001 PM 21155761 ER PT J AU Hadley, DW Ashida, S Jenkins, JF Calzone, KA Kirsch, IR Koehly, LM AF Hadley, D. W. Ashida, S. Jenkins, J. F. Calzone, K. A. Kirsch, I. R. Koehly, L. M. TI Colonoscopy use following mutation detection in Lynch syndrome: exploring a role for cancer screening in adaptation SO CLINICAL GENETICS LA English DT Article DE colonoscopy; genetic testing; health behavior; HNPCC; L ynch syndrome ID NONPOLYPOSIS COLORECTAL-CANCER; COLON-CANCER; PSYCHOLOGICAL IMPACT; ENDOMETRIAL CANCER; DISTRESS; FAMILIES; HEALTH; HNPCC; SUSCEPTIBILITY; INDIVIDUALS AB Lynch syndrome (LS) is the most common inherited form of colorectal cancer. Mutation carriers can reduce the morbidity and mortality associated with colorectal cancer through colonoscopy. Theoretical models suggest that such health-related behaviors might also bring psychological benefits. This study assessed whether colonoscopy following mutation detection was associated with the levels of depressive symptoms. Data were obtained from a prospective family cohort study offering genetic services for LS. Participants completed questionnaires prior to the provision of services and 6 months post-receipt of mutation results. One hundred thirty-four (134) persons were identified to carry a mutation and completed both the questionnaires. Main outcome measures were depressive symptoms 6 months post-receipt of test results. Mutation carriers who did not complete a colonoscopy within the 6 months following receipt of results were six times (p < 0.01; odds ratio = 6.06) more likely to report depressive symptoms at a level of clinical importance post-receipt of test results compared to those who did undergo colonoscopy. Facilitating the expeditious use of colonoscopy following mutation detection may benefit newly identified mutation carriers by addressing the objective risks for cancer and moderating underlying emotional distress responses to genetic risk information. Furthermore, depressive symptoms may interfere with behavioral compliance in some patients, suggesting referral to mental health specialists. C1 [Hadley, D. W.] NHGRI, Social & Behav Res Branch, NIH, DHHS,Social Network Methods Sect, Bethesda, MD 20892 USA. [Ashida, S.] Univ Memphis, Div Social & Behav Sci, Sch Publ Hlth, Memphis, TN 38152 USA. [Jenkins, J. F.] NHGRI, NIH, Off Director, Bethesda, MD 20892 USA. [Calzone, K. A.; Kirsch, I. R.] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Hadley, DW (reprint author), NHGRI, Social & Behav Res Branch, NIH, DHHS,Social Network Methods Sect, 31 Ctr Dr,MSC 2073,Bldg 31,Room B1B37F, Bethesda, MD 20892 USA. EM dhadley@mail.nih.gov FU National Human Genome Research Institute; National Cancer Institute at the NIH in Bethesda, Maryland (USA) [Z01 000059-11] FX We thank our participants for the willingness to share their lives with us, for without their efforts this work would not be possible. We also thank Shoshanna Shiloh, PhD, for her comprehensive review and constructive critique of the manuscript during its preparation. This research was supported by the Intramural Research Programs of the National Human Genome Research Institute and the National Cancer Institute at the NIH in Bethesda, Maryland (USA). [Z01 000059-11; PI: Koehly]. NR 28 TC 5 Z9 5 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD APR PY 2011 VL 79 IS 4 BP 321 EP 328 DI 10.1111/j.1399-0004.2010.01622.x PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 730FJ UT WOS:000288018700002 PM 21204803 ER PT J AU Salvador, R Silva, S Basser, PJ Miranda, PC AF Salvador, R. Silva, S. Basser, P. J. Miranda, P. C. TI Determining which mechanisms lead to activation in the motor cortex: A modeling study of transcranial magnetic stimulation using realistic stimulus waveforms and sulcal geometry SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE Transcranial magnetic stimulation; TMS; Activation; Mechanism; Motor cortex; FEM ID PERIPHERAL-NERVE; CONSCIOUS HUMANS; ELECTRIC-FIELDS; CEREBRAL-CORTEX; SPINAL-CORD; ELECTROMAGNETIC INDUCTION; SOMATOSENSORY CORTEX; TISSUE HETEROGENEITY; CORTICAL STIMULATION; BRAIN-STIMULATION AB Objective: To determine which mechanisms lead to activation of neurons in the motor cortex during transcranial magnetic stimulation (TMS) with different current directions and pulse waveforms. Methods: The total electric field induced in a simplified model of a cortical sulcus by a figure-eight coil was calculated using the finite element method (FEM). This electric field was then used as the input to determine the response of compartmental models of several types of neurons. Results: The modeled neurons were stimulated at different sites: fiber bends for pyramidal tract neurons, axonal terminations for cortical interneurons and axon collaterals, and a combination of both for pyramidal association fibers. All neurons were more easily stimulated by a PA-directed electric field, except association fibers. Additionally, the second phase of a biphasic pulse was found to be more efficient than the first phase of either monophasic or biphasic pulses. Conclusions: The stimulation threshold for different types of neurons depends on the pulse waveform and relative current direction. The reported results might account for the range of responses obtained in TMS of the motor cortex when using different stimulation parameters. Significance: Modeling studies combining electric field calculations and neuronal models may lead to a deeper understanding of the effect of the TMS-induced electric field on cortical tissue, and may be used to improve TMS coil and waveform design. (C) 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 [Salvador, R.; Silva, S.; Miranda, P. C.] Univ Lisbon, Fac Sci, Inst Biophys & Biomed Engn, P-1749016 Lisbon, Portugal. [Basser, P. J.] NICHD, Sect Tissue Biophys & Biomimet, NIH, Bethesda, MD 20892 USA. RP Salvador, R (reprint author), Univ Lisbon, Fac Sci, Inst Biophys & Biomed Engn, P-1749016 Lisbon, Portugal. EM rnsalvador@fc.ul.pt; ssilva@fc.ul.pt RI Miranda, Pedro/A-5643-2013; Basser, Peter/H-5477-2011; Salvador, Ricardo/K-2301-2015 OI Miranda, Pedro/0000-0002-6793-8111; Salvador, Ricardo/0000-0003-1235-6533 FU Foundation for Science and Technology (FCT), Portugal; NICHD, NIH, USA; FCT [SFRH/BD/23537/2005, SFRH/BD/13815/2003] FX This work was supported by the Foundation for Science and Technology (FCT), Portugal and by the Intramural Research Program of the NICHD, NIH, USA. R. Salvador and S. Silva gratefully acknowledge the support of FCT under Grants Nos. SFRH/BD/23537/2005 and SFRH/BD/13815/2003. NR 58 TC 47 Z9 47 U1 2 U2 15 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 EI 1872-8952 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD APR PY 2011 VL 122 IS 4 BP 748 EP 758 DI 10.1016/j.clinph.2010.09.022 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 730VP UT WOS:000288063600020 PM 21035390 ER PT J AU von Leupoldt, A Keil, A Davenport, PW AF von Leupoldt, Andreas Keil, Andreas Davenport, Paul W. TI Respiratory-related evoked potential measurements using high-density electroencephalography SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE EEG; Perception; Respiratory-related evoked potential; Signal-to-noise ratio ID INSPIRATORY OCCLUSION; HUMANS AB Objective: The respiratory-related evoked potential (RREP) has become an established technique for studying the neural processing of respiratory signals. However, the increasing availability of high-density EEG systems necessitates new criteria for obtaining acceptable RREPs with these systems. Methods: The present study examined the minimum criteria for the number of inspiratory occlusions that need to be averaged in order to obtain a signal-to-noise ratio of 2: 1 (3 dB) for the RREP components Nf, P1, N1, P2 and P3 with a 129 sensor high-density EEG system in 12 healthy volunteers. RREPs resulting from averaging 8, 16, 32 and 64 inspiratory occlusions were compared. Results: Analyses of signal-to-noise ratios demonstrated that a minimum of 32 and 16 inspiratory occlusions should be averaged for Nf and P1, respectively. For N1, P2, and P3, an average of at least 8 inspiratory occlusions is required. However, to account for inter-individual variability, 64 averaged occlusions for Nf, 32 averaged occlusions for P1, and 16 averaged occlusions for N1, P2, and P3 are recommended which more reliably exceed the signal-to-noise threshold. Conclusions: These numbers provide the minimum and the recommended criteria for reliable measurements of the RREP for an adequate number of repeated occlusion epochs to be averaged in order to yield a reliable signal-to-noise ratio using a 129 sensor EEG system. Significance: The present study provides minimum and recommended criteria for obtaining acceptable RREPs with high-density EEG systems. (C) 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 [von Leupoldt, Andreas] Univ Hamburg, Dept Psychol, D-20146 Hamburg, Germany. [von Leupoldt, Andreas; Davenport, Paul W.] Univ Florida, Dept Physiol Sci, Gainesville, FL 32610 USA. [von Leupoldt, Andreas] Univ Med Ctr Hamburg Eppendorf, Dept Syst Neurosci, Hamburg, Germany. [von Leupoldt, Andreas; Keil, Andreas] Univ Florida, NIMH Ctr Study Emot & Attent, Gainesville, FL USA. RP von Leupoldt, A (reprint author), Univ Hamburg, Dept Psychol, Von Melle Pk 5, D-20146 Hamburg, Germany. EM andreas.vonleupoldt@uni-hamburg.de RI Keil, Andreas/F-9427-2011 OI Keil, Andreas/0000-0002-4064-1924 FU German Research Society (Deutsche Forschungsgemeinschaft, DFG) [LE 1843/9-1]; National Institute of Mental Health [P50 MH 72850] FX The authors wish to thank Peter J. Lang and Margaret M. Bradley for their valuable support of this work. The study was supported by a stipend (Heisenberg-Stipendium, DFG LE 1843/9-1) from the German Research Society (Deutsche Forschungsgemeinschaft, DFG) to Andreas von Leupoldt and by a grant from the National Institute of Mental Health (P50 MH 72850) to Peter J. Lang. The funding sources had no impact on the study design, data collection/inter-pretation or preparation of the present manuscript. All authors report no conflict of interests. NR 12 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD APR PY 2011 VL 122 IS 4 BP 815 EP 818 DI 10.1016/j.clinph.2010.10.031 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 730VP UT WOS:000288063600029 PM 21067971 ER PT J AU Meier, JKH Wolff, D Pavletic, S Greinix, H Gosau, M Bertz, H Lee, SJ Lawitschka, A Elad, S AF Meier, Johannes K. -H. Wolff, Daniel Pavletic, Steve Greinix, Hildegard Gosau, Martin Bertz, Hartmut Lee, Stefanie J. Lawitschka, Anita Elad, Sharon TI Oral chronic graft-versus-host disease: report from the International Consensus Conference on clinical practice in cGVHD SO CLINICAL ORAL INVESTIGATIONS LA English DT Review DE Oral cGVHD; Topical Treatment; Diagnosis ID BONE-MARROW-TRANSPLANTATION; WORKING GROUP-REPORT; BISPHOSPHONATE-RELATED OSTEONECROSIS; HEMATOPOIETIC-CELL TRANSPLANTATION; SURGEONS POSITION PAPER; TOPICAL TACROLIMUS; DEVELOPMENT PROJECT; MULTIPLE-MYELOMA; RISK-FACTORS; PILOCARPINE HYDROCHLORIDE AB Chronic graft-versus-host disease (cGVHD) is a multi-organ disease that occurs post-hematopoietic stem cell transplantation, with the mouth being one of the most frequently affected organs. In 2009, the German-Austrian-Swiss working party on bone marrow and blood stem cell transplantation held a consensus conference to define clinical management of cGVHD. The consensus conference aimed to summarize the literature on diagnosis and topical treatment options for oral cGVHD and to provide recommendations for clinical practice, including routine dental and oral care as well as monitoring for secondary malignancies and bisphophonate-induced osteonecrosis of the jaw. C1 [Elad, Sharon] Hebrew Univ Jerusalem, Hadassah Sch Dent Med, Dept Oral Med, IL-91120 Jerusalem, Israel. [Meier, Johannes K. -H.; Gosau, Martin] Univ Regensburg, Dept Craniomaxillofacial Surg, Regensburg, Germany. [Wolff, Daniel] Univ Regensburg, Dept Haematol & Oncol, Regensburg, Germany. [Pavletic, Steve] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Greinix, Hildegard] Med Univ Vienna, Dept Internal Med 1, Vienna, Austria. [Bertz, Hartmut] Univ Freiburg, Dept Haematol & Oncol, Med Ctr Freiburg, Freiburg, Germany. [Lee, Stefanie J.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Lawitschka, Anita] St Anna Childrens Hosp, Dept Stem Cell Transplantat, A-1090 Vienna, Austria. RP Elad, S (reprint author), Hebrew Univ Jerusalem, Hadassah Sch Dent Med, Dept Oral Med, POB 12272, IL-91120 Jerusalem, Israel. EM sharonela@ekmd.huji.ac.il NR 88 TC 27 Z9 29 U1 0 U2 4 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1432-6981 J9 CLIN ORAL INVEST JI Clin. Oral Investig. PD APR PY 2011 VL 15 IS 2 BP 127 EP 139 DI 10.1007/s00784-010-0450-6 PG 13 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 733IK UT WOS:000288256200001 PM 20859645 ER PT J AU Ramos, E Chen, G Shriner, D Doumatey, A Gerry, NP Herbert, A Huang, H Zhou, J Christman, MF Adeyemo, A Rotimi, C AF Ramos, E. Chen, G. Shriner, D. Doumatey, A. Gerry, N. P. Herbert, A. Huang, H. Zhou, J. Christman, M. F. Adeyemo, A. Rotimi, C. TI Replication of genome-wide association studies (GWAS) loci for fasting plasma glucose in African-Americans SO DIABETOLOGIA LA English DT Article DE African-American; Association; GWAS; Replication; Type 2 diabetes ID LINKAGE DISEQUILIBRIUM; SUSCEPTIBILITY; POPULATIONS; PATTERNS; DISEASE AB Chronically elevated blood glucose (hyperglycaemia) is the primary indicator of type 2 diabetes, which has a prevalence that varies considerably by ethnicity in the USA, with African-Americans disproportionately affected. Genome-wide association studies (GWASs) have significantly enhanced our understanding of the genetic basis of diabetes and related traits, including fasting plasma glucose (FPG). However, the majority of GWASs have been conducted in populations of European ancestry. Thus, it is important to conduct replication analyses in populations with non-European ancestry to identify shared loci associated with FPG across populations. We used data collected from non-diabetic unrelated African-American individuals (n = 927) who participated in the Howard University Family Study to attempt to replicate previously published GWASs of FPG. Of the 29 single nucleotide polymorphisms (SNPs) previously reported, we directly tested 20 in this study. In addition to the direct test, we queried a 500 kb window centred on all 29 reported SNPs for local replication of additional markers in linkage disequilibrium (LD). Using direct SNP and LD-based comparisons, we replicated multiple SNPs previously associated with FPG and strongly associated with type 2 diabetes in populations with European ancestry. The replicated SNPs included those in or near TCF7L2, SLC30A8, G6PC2, MTNR1B, DGKB-TMEM195 and GCKR. We also replicated additional variants in LD with the reported SNPs in ZMAT4 and adjacent to IRS1. We identified multiple GWAS variants for FPG in our cohort of African-Americans. Using an LD-based strategy we also identified SNPs not previously reported, demonstrating the utility of using diverse populations for replication analysis. C1 [Ramos, E.; Chen, G.; Shriner, D.; Doumatey, A.; Huang, H.; Zhou, J.; Adeyemo, A.; Rotimi, C.] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA. [Gerry, N. P.; Christman, M. F.] Coriell Inst Med Res, Camden, NJ USA. [Herbert, A.] Boston Univ, Sch Med, Dept Genet & Genom, Boston, MA 02118 USA. RP Rotimi, C (reprint author), NHGRI, Ctr Res Genom & Global Hlth, NIH, 12 South Dr,MSC 5635, Bethesda, MD 20892 USA. EM rotimic@mail.nih.gov OI Adeyemo, Adebowale/0000-0002-3105-3231 FU National Institutes of Health [S06GM008016-320107, S06GM008016-380111, 2M01RR010284]; National Human Genome Research Institute; National Institute of Diabetes and Digestive and Kidney Diseases; Center for Information Technology; Office of the Director at the National Institutes of Health [Z01HG200362] FX The HUFS was supported by National Institutes of Health grants S06GM008016-320107 to C. Rotimi and S06GM008016-380111 to A. Adeyemo. We thank the participants of the study, for which enrolment was carried out at the Howard University General Clinical Research Center, supported by National Institutes of Health grant 2M01RR010284. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official view of the National Institutes of Health. This research was supported in part by the Intramural Research Program of the Center for Research on Genomics and Global Health, which is supported by the National Human Genome Research Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the Center for Information Technology and the Office of the Director at the National Institutes of Health (Z01HG200362). Genotyping support was provided by the Coriell Institute for Medical Research. NR 13 TC 33 Z9 34 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD APR PY 2011 VL 54 IS 4 BP 783 EP 788 DI 10.1007/s00125-010-2002-7 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 732VG UT WOS:000288217200011 PM 21188353 ER PT J AU Lau, SM Lin, S Stokes, RA Cheng, K Baldock, PA Enriquez, RF McLean, M Cheung, NW Sainsbury, A Gonzalez, FJ Herzog, H Gunton, JE AF Lau, S. M. Lin, S. Stokes, R. A. Cheng, K. Baldock, P. A. Enriquez, R. F. McLean, M. Cheung, N. W. Sainsbury, A. Gonzalez, F. J. Herzog, H. Gunton, J. E. TI Synergistic effects of genetic beta cell dysfunction and maternal glucose intolerance on offspring metabolic phenotype in mice SO DIABETOLOGIA LA English DT Article DE ARNT; Beta cell; Energy expenditure; Gestational diabetes; Obesity; Pregnancy; Programming ID GESTATIONAL DIABETES-MELLITUS; INTRAUTERINE ENVIRONMENT; PREGNANCY OUTCOMES; INSULIN-SECRETION; GUT MICROBIOME; WEIGHT-GAIN; MOTHERS; OBESITY; WOMEN; RISK AB Diabetes in pregnancy is linked to development of obesity in the offspring, but the mechanisms are not fully understood. Gestational diabetes mellitus (GDM) occurs when beta cells are unable to compensate for the normal insulin resistance of late pregnancy. In this study, we used a murine model of beta cell dysfunction to examine the effects of maternal GDM on phenotype in male offspring with and without an inherited predisposition for beta cell dysfunction. Beta cell-specific aryl-hydrocarbon receptor nuclear translocator-null (beta Arnt) mice develop GDM from beta cell dysfunction. beta Arnt and control female mice were used to induce GDM and non-diabetic pregnancies, respectively. Offspring from GDM pregnancies became spontaneously obese on a normal-chow diet. They were heavier than offspring from non-diabetic pregnancies, with increased body fat. Respiratory exchange ratio (RER) was higher, indicating decreased capacity to switch to lipid oxidation. Metabolic rate in GDM offspring was decreased prior to onset of obesity. The phenotype was more pronounced in beta Arnt GDM offspring than in GDM offspring of control genotype, demonstrating an interaction between genotype and pregnancy exposure. beta Arnt GDM offspring had increased hypothalamic neuropeptide Y (Npy) and decreased pro-opiomelanocortin (Pomc) expression. Weight, body fat, insulin sensitivity and RER in all mice, and hypothalamic Npy in beta Arnt mice were significantly correlated with AUC of maternal late pregnancy glucose tolerance tests (p < 0.01), but not with litter size, maternal weight, triacylglycerol or pre-pregnancy glycaemia. In beta Arnt mice, exposure to GDM and inheritance of genetic beta cell dysfunction had additive effects on male offspring obesity; severity of the offspring phenotype correlated with maternal glycaemia. C1 [Lau, S. M.; Gunton, J. E.] Univ Sydney, Fac Med, Sydney, NSW 2006, Australia. [Lau, S. M.; Stokes, R. A.; Cheng, K.; Gunton, J. E.] St Vincents Hosp, Garvan Inst Med Res, Diabet & Transcript Factors Grp, Darlinghurst, NSW 2010, Australia. [Lau, S. M.; Gunton, J. E.] Westmead Hosp, Dept Endocrinol & Diabet, Sydney, NSW, Australia. [Lau, S. M.; Gunton, J. E.] Univ New S Wales, St Vincents Clin Sch, Sydney, NSW, Australia. [Lin, S.; Sainsbury, A.; Herzog, H.] Garvan Inst Med Res, Neurosci Program, Sydney, NSW, Australia. [Baldock, P. A.; Enriquez, R. F.] Garvan Inst Med Res, Bone & Mineral Res Program, Sydney, NSW, Australia. [McLean, M.; Cheung, N. W.] Westmead Hosp, Ctr Diabet & Endocrinol Res, Sydney, NSW, Australia. [Sainsbury, A.] Univ New S Wales, Sch Med Sci, Sydney, NSW, Australia. [Gonzalez, F. J.] NIH, Lab Metab, Bethesda, MD 20892 USA. RP Gunton, JE (reprint author), Univ Sydney, Fac Med, Sydney, NSW 2006, Australia. EM j.gunton@garvan.org.au RI Sainsbury, Amanda/A-3187-2011; Baldock, Paul/B-3840-2012; Gunton, Jenny/E-1561-2012; Lin, Shu/A-4361-2010 OI Sainsbury, Amanda/0000-0001-9176-1574; FU National Heart Foundation; NHMRC/DART; L'Oreal Australian Women in Science Fellowship; NHMRC; DART; Endocrine Society of Australia; Australasian Society for Diabetes in Pregnancy FX The authors would like to acknowledge K. Byth (Westmead Hospital) for her assistance with statistics, and A. Dwyer (Concord Hospital, Sydney, NSW, Australia), C. Nolan (Australian National University, Canberra, ACT, Australia) and D. Chisholm (Garvan Institute) for helpful comments on the manuscript. S. M. Lau received salary support from the National Heart Foundation. J. E. Gunton received an NHMRC/DART fellowship and a L'Oreal Australian Women in Science Fellowship. P. A. Baldock, H. Herzog and A. Sainsbury received NHMRC fellowships. The work was partially supported by funds from DART, Endocrine Society of Australia and the Australasian Society for Diabetes in Pregnancy. NR 39 TC 8 Z9 9 U1 1 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD APR PY 2011 VL 54 IS 4 BP 910 EP 921 DI 10.1007/s00125-010-1998-z PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 732VG UT WOS:000288217200025 PM 21181398 ER PT J AU Bagnato, F Centonze, D Galgani, S Grasso, MG Haggiag, S Strano, S AF Bagnato, Francesca Centonze, Diego Galgani, Simonetta Grasso, Maria Grazia Haggiag, Shalom Strano, Stefano TI Painful and involuntary multiple sclerosis SO EXPERT OPINION ON PHARMACOTHERAPY LA English DT Review DE dysautonomia; MS; pain; pharmacotherapy ID QUALITY-OF-LIFE; CARDIOVASCULAR AUTONOMIC DYSFUNCTION; DIRECT-CURRENT STIMULATION; SEXUAL DYSFUNCTION; DOUBLE-BLIND; ERECTILE DYSFUNCTION; NEUROPATHIC PAIN; ORTHOSTATIC INTOLERANCE; TRIGEMINAL NEURALGIA; SILDENAFIL CITRATE AB Introduction: Pain, dysphagia, respiratory problems, sexual and cardiovascular dysfunctions may occur in patients with MS. Areas covered: In the present review, we attempt to summarize the current knowledge on the impact pain, dysphagia, respiratory problems, sexual and cardiovascular dysfunctions have in patients with MS. Expert opinion: To effectively manage MS, it is essential that these symptoms are recognized as early as possible and treated by a rehabilitative multidisciplinary approach, based on proven scientific evidence. C1 [Bagnato, Francesca] Vanderbilt Univ, Inst Imaging Sci, Dept Radiol, Nashville, TN 37232 USA. [Centonze, Diego] Tor Vergata Univ & Hosp, Multiple Sclerosis MS Clin Ctr CC, Rome, Italy. [Centonze, Diego; Grasso, Maria Grazia] Santa Lucia Fdn Sci Res Inst, Rome, Italy. [Galgani, Simonetta; Haggiag, Shalom] San Camillo Forlanini Hosp, MS CC, Rome, Italy. [Strano, Stefano] Univ Roma La Sapienza, Dept Cardiocirculatory Phisiopathol Anesthesiol &, Rome, Italy. [Bagnato, Francesca] NINDS, NIH, Bethesda, MD 20892 USA. RP Bagnato, F (reprint author), Vanderbilt Univ, Inst Imaging Sci, Dept Radiol, 1161 21st Ave S AA1105 MCN, Nashville, TN 37232 USA. EM francesca.r.bagnato@vanderbilt.edu OI grasso, maria grazia/0000-0003-1582-5534; Centonze, Diego/0000-0002-8390-8545 FU Intramural NIH HHS [Z99 NS999999] NR 121 TC 4 Z9 5 U1 0 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1465-6566 J9 EXPERT OPIN PHARMACO JI Expert Opin. Pharmacother. PD APR PY 2011 VL 12 IS 5 BP 763 EP 777 DI 10.1517/14656566.2011.540239 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 732VS UT WOS:000288218400008 PM 21323633 ER PT J AU Broedbaek, K Siersma, V Andersen, JT Petersen, M Afzal, S Hjelvang, B Weimann, A Semba, RD Ferrucci, L Poulsen, HE AF Broedbaek, Kasper Siersma, Volkert Andersen, Jon T. Petersen, Morten Afzal, Shoaib Hjelvang, Brian Weimann, Allan Semba, Richard D. Ferrucci, Luigi Poulsen, Henrik E. TI The association between low-grade inflammation, iron status and nucleic acid oxidation in the elderly SO FREE RADICAL RESEARCH LA English DT Article DE DNA oxidation; inflammation; iron; 8-hydroxy-2 '-deoxyguanosine; 8-oxo-7,8-dihydro-2 '-deoxyguanosine; 8-oxodG; 8-oxo-7,8-dihydroguanosine; 8-oxoGuo ID C-REACTIVE PROTEIN; HELICOBACTER-PYLORI INFECTION; CORONARY-HEART-DISEASE; DNA-DAMAGE; BODY IRON; HEALTHY PEOPLE; STRESS; CANCER; WOMEN; MEN AB This study applied a case-control approach to investigate the association between low-grade inflammation, defined by high values within the normal range of C-reactive protein (CRP) and interleukin-6 (IL-6), and urinary markers of nucleic acid oxidation. No differences in excretion of urinary markers of nucleic acid oxidation between cases and controls were found and multivariable linear regression analysis showed no association between urinary markers of nucleic acid oxidation and inflammatory markers. Post-hoc multivariable linear regression analysis showed significant associations between nucleic acid oxidation and various iron status markers and especially a close relationship between nucleic acid oxidation and ferritin. This study shows no association between low-grade inflammation and urinary markers of nucleic acid oxidation in a population of elderly Italian people. The results suggest that low-grade inflammation only has a negligible impact on whole body nucleic acid oxidation, whereas iron status seems to be of great importance. C1 [Broedbaek, Kasper; Andersen, Jon T.; Petersen, Morten; Afzal, Shoaib; Hjelvang, Brian; Weimann, Allan; Poulsen, Henrik E.] Rigshosp, Lab Clin Pharmacol Q7642, DK-2200 Copenhagen, Denmark. [Broedbaek, Kasper; Andersen, Jon T.; Petersen, Morten; Afzal, Shoaib; Hjelvang, Brian; Weimann, Allan; Poulsen, Henrik E.] Bispebjerg Hosp, Dept Clin Pharmacol, DK-2400 Copenhagen, Denmark. [Siersma, Volkert] Univ Copenhagen, Dept Publ Hlth, Sect Gen Practice, Res Unit Gen Practice, Copenhagen, Denmark. [Semba, Richard D.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. [Poulsen, Henrik E.] Univ Copenhagen, Fac Hlth Sci, Copenhagen, Denmark. RP Broedbaek, K (reprint author), Rigshosp, Lab Clin Pharmacol Q7642, Tagensvej 20, DK-2200 Copenhagen, Denmark. EM kasper.broedbaek@rh.regionh.dk RI Afzal, Shoaib/B-6763-2012; Brodbak, Kasper/G-5115-2012; Siersma, Volkert/G-6867-2016 OI Afzal, Shoaib/0000-0002-1442-4694; Siersma, Volkert/0000-0003-1941-2681 FU Research Committee at Copenhagen University Hospital-Rigshospitalet FX This study was supported by research funding from the Research Committee at Copenhagen University Hospital-Rigshospitalet. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. NR 32 TC 9 Z9 9 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1071-5762 J9 FREE RADICAL RES JI Free Radic. Res. PD APR PY 2011 VL 45 IS 4 BP 409 EP 416 DI 10.3109/10715762.2010.538391 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 732VI UT WOS:000288217400004 PM 21275071 ER PT J AU Peluso, M Munnia, A Risso, GG Catarzi, S Piro, S Ceppi, M Giese, RW Brancato, B AF Peluso, Marco Munnia, Armelle Risso, Gabriella G. Catarzi, Sandra Piro, Sara Ceppi, Marcello Giese, Roger W. Brancato, Beniamino TI Breast fine-needle aspiration malondialdehyde deoxyguanosine adduct in breast cancer SO FREE RADICAL RESEARCH LA English DT Article DE Breast cancer; free radicals; M(1)dG; fine-needle aspirate; tumour grade; pathological diameter ID DNA-ADDUCTS; LIPID-PEROXIDATION; OXIDATIVE STRESS; LUNG-CANCER; ANTIOXIDANT STATUS; DAMAGE; CELLS; CARCINOGENESIS; INFLAMMATION; CARCINOMA AB This study has analysed the generation of 3-(2-deoxy-beta-D-erythro-pentafuranosyl)pyrimido[1,2-a]purin-10(3H)-one deoxyguanosine adduct [M(1)dG], a biomarker of oxidative stress and lipid peroxidation, in breast fine-needle aspirate samples of 22 patients with breast cancer, at different clinical stages, in respect to 13 controls. The multivariate analysis show that M(1)dG adduct was higher in cases than in controls (Mean Ratio (MR) = 5.26, 95% CI = 3.16-8.77). Increased M(1)dG was observed in women with a tumour grade 3 and a pathological diameter 2 (MR = 7.61, 95% CI = 3.91-14.80 and MR = 5.75, 95% CI = 3.13-10.59, respectively). A trend with increasing tumour grade and pathological diameter was present (MR = 1.98, 95% CI = 1.57-2.50 and MR = 2.44, 95% CI = 1.71-3.48, respectively). Not significant effects of age and smoking habit were found (MR = 1.58, 95% CI = 0.92-2.72 and MR = 1.68, 95% CI 0.88-3.20, respectively). An increment over the background frequency of M(1)dG can contribute to breast cancer development. Increasing severity of breast tumour can influence DNA damage level. C1 [Peluso, Marco] ISPO Canc Prevent & Res Inst, Analyt & Biomol Cytol Unit, Canc Risk Factor Branch, I-50139 Florence, Italy. [Ceppi, Marcello] Natl Canc Inst, Mol Epidemiol Unit, Genoa, Italy. [Giese, Roger W.] Northeastern Univ, Barnett Inst, Dept Pharmaceut Sci, Bouve Coll Hlth Sci, Boston, MA 02115 USA. RP Peluso, M (reprint author), ISPO Canc Prevent & Res Inst, Analyt & Biomol Cytol Unit, Canc Risk Factor Branch, Via Cosimo Vecchio 2, I-50139 Florence, Italy. EM m.peluso@ispo.toscana.it OI PIRO, SARA/0000-0003-4198-7035 FU 'Associazione Italiana per la Ricerca sul Cancro', Milan, Italy; NIEHS [P42ES017198] FX This work was supported in part by the 'Associazione Italiana per la Ricerca sul Cancro', Milan, Italy and in part by Award Number P42ES017198 from NIEHS. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. NR 32 TC 20 Z9 20 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1071-5762 J9 FREE RADICAL RES JI Free Radic. Res. PD APR PY 2011 VL 45 IS 4 BP 477 EP 482 DI 10.3109/10715762.2010.549485 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 732VI UT WOS:000288217400012 PM 21250785 ER PT J AU Mannon, PJ Hornung, RL Yang, ZQ Yi, CL Groden, C Friend, J Yao, M Strober, W Fuss, IJ AF Mannon, Peter J. Hornung, Ronald L. Yang, Zhiqiong Yi, Chuli Groden, Catherine Friend, Julia Yao, Michael Strober, Warren Fuss, Ivan J. TI Suppression of inflammation in ulcerative colitis by interferon-beta-1a is accompanied by inhibition of IL-13 production SO GUT LA English DT Article ID NK-T-CELLS; PLACEBO-CONTROLLED TRIAL; MULTIPLE-SCLEROSIS; CYTOKINE SECRETION; REGULATORY CELLS; DOUBLE-BLIND; ALPHA; BETA; EXPRESSION; DIFFERENTIATION AB Objective Ulcerative colitis is associated with increased interleukin 13 (IL-13) production by natural killer T cells. Taking advantage of the inhibitory actions of interferon beta on IL-13 expression, this proof-of-concept study aimed to show that decreasing IL-13 production is associated with clinical improvement of ulcerative colitis symptoms. Design Open-label interventional drug trial. Setting Outpatient clinical research hospital. Patients Adult patients with active ulcerative colitis (Short Clinical Colitis Activity Index (SCCAI)>= 5). Interventions Treatment with 30 mu g IM interferon-beta-1a (Avonex) weekly for 12 weeks with 6 month follow-up. Main outcome measures Clinical response was defined as >= 3 point drop in the SCCAI for at least two consecutive monitoring visits, and cytokine production was measured in cultured peripheral blood and lamina propria mononuclear cells (LPMC) before and after treatment. Results 11 of 16 patients were clinical responders, and 4 were in remission (SCCAI <= 2) at the end of treatment. Rectal bleeding subscores improved dramatically by week 4 (38% with frank bleeding vs 87% pretreatment). Increased IL-13 production by LPMC T cells fell significantly in clinical responders (690 +/- 99 vs 297 +/- 58 pg/ml p=0.015) but was unchanged in non-responders (542 +/- 83 vs 510 +/- 39 pg/ml). In addition, non-responders had significantly higher production of IL-17 and IL-6 pre-treatment compared to responders. Conclusions Interferon-beta-1a induces clinical response and remission in a large subset of patients with ulcerative colitis that is associated with significant inhibition of IL-13 production. In addition, increased IL-17 and IL-6 production is associated with no response to interferon-beta. These data provide a proof-of-concept that IL-13 is an effector cytokine in ulcerative colitis and should be a target for novel therapies. C1 [Mannon, Peter J.; Yang, Zhiqiong; Yi, Chuli; Groden, Catherine; Friend, Julia; Yao, Michael; Strober, Warren; Fuss, Ivan J.] NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. [Hornung, Ronald L.] NCI, Clin Serv Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Mannon, PJ (reprint author), Univ Alabama, 1825 Univ Blvd,SHEL 613, Birmingham, AL 35294 USA. EM pmannon@uab.edu FU Division of Intramural Research, NIAID; NIH Clinical Center; National Cancer Institute [N01-CO-12400]; Biogen-Idec FX This project has been funded by the Division of Intramural Research, NIAID, the NIH Clinical Center and the National Cancer Institute under contract N01-CO-12400.; PM has received consultant fees from Biogen-Idec. NR 28 TC 45 Z9 46 U1 1 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD APR PY 2011 VL 60 IS 4 BP 449 EP 455 DI 10.1136/gut.2010.226860 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 730CZ UT WOS:000288010600009 PM 20971977 ER PT J AU Zhang, XC Ross, TJ Salmeron, BJ Yang, SL Yang, YH Stein, EA AF Zhang, Xiaochu Ross, Thomas J. Salmeron, Betty Jo Yang, Shaolin Yang, Yihong Stein, Elliot A. TI Single Subject Task-Related BOLD Signal Artifact in a Real-Time fMRI Feedback Paradigm SO HUMAN BRAIN MAPPING LA English DT Article DE real-time feedback; fMRI; artifact; eyeball motion; individual data ID FUNCTIONAL MRI; NEUROFEEDBACK; PERFORMANCE; BRAIN; SUPPRESSION; ATTENTION; MOTION AB Real-time functional magnetic resonance imaging (rtfMRI) has been proposed as a method of providing feedback to develop a participant's ability to control his or her own neuronal activity. However, this BOLD signal is vulnerable to contamination from nonneuronal sources that can also be shaped by the feedback provided. Here we illustrate an artifact found while training participants to control signal from an ROI in the insula. As the artifact was directly behind the eye and the experiment used an echo-planar imaging (EPI) sequence with phase encoding direction that included the orbits and the insula in the same line, we hypothesized that the artifact was due to eye motion. We demonstrate a reduced training effect when eyeball signal is regressed out of the data and reproduce the artifact with block design voluntary eye movement. Further, using independent components analysis on historical data, we find the artifact is common in BOLD data, but typically not task-correlated, even in tasks where one might expect differing amounts of eye movement in the active task blocks. The artifact, thus, does not significantly impact group results in typical fMRI experiments. Finally, we demonstrate this particular artifact can be avoided in rtfMRI experiments by ensuring that the phase encoding direction does not project any eye movement related artifact onto the ROI being used for feedback training. Our findings underscore the importance of taking great care in designing rtfMRI feedback procedures to avoid contamination with nonneuronal sources of BOLD signal alteration. Hum Brain Mapp 32:592-600, 2011. (C) 2010 Wiley-Liss, Inc. C1 [Zhang, Xiaochu; Ross, Thomas J.; Salmeron, Betty Jo; Yang, Shaolin; Yang, Yihong; Stein, Elliot A.] NIDA, Neuroimaging Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Stein, EA (reprint author), NIDA, Neuroimaging Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. EM estein@mail.nih.gov RI Ross, Thomas/B-7469-2008; Zhang, Xiaochu/O-9592-2014; Salmeron, Betty Jo/M-1793-2016 OI Ross, Thomas/0000-0002-7745-3572; Zhang, Xiaochu/0000-0002-7541-0130; Salmeron, Betty Jo/0000-0003-1699-9333 FU National Institute on Drug Abuse; NIH FX Contract grant sponsors: Intramural Research Program of the National Institute on Drug Abuse; NIH. NR 24 TC 6 Z9 6 U1 1 U2 12 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD APR PY 2011 VL 32 IS 4 BP 592 EP 600 DI 10.1002/hbm.21046 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 732ID UT WOS:000288177300007 PM 21391249 ER PT J AU Lee, YS Amadi-Obi, A Yu, CR Egwuagu, CE AF Lee, Yun Sang Amadi-Obi, Ahjoku Yu, Cheng-Rong Egwuagu, Charles E. TI Retinal cells suppress intraocular inflammation (uveitis) through production of interleukin-27 and interleukin-10 SO IMMUNOLOGY LA English DT Article DE cytokine; interleukin-10; interleukin-27; intraocular inflammatory diseases; microglia; retina; signal transducer and activator of transcription 1 ID EXPERIMENTAL AUTOIMMUNE UVEITIS; CYTOKINE-SIGNALING PROTEINS; CD4(+) T-CELLS; LINEAGE COMMITMENT; IL-2 PRODUCTION; SOCS PROTEINS; ENCEPHALOMYELITIS; RECEPTOR; DISEASE; STAT1 AB P>Neuronal or photoreceptor deficit observed in uveitis and multiple sclerosis derives in part from inability to control inflammatory responses in neuroretina or brain. Recently, IL-27 was found to play a role in suppressing experimental autoimmune uveitis and experimental autoimmune encephalomyelitis, two animal models that share essential pathological features of human uveitis and multiple sclerosis, respectively. However, the mechanism by which interleukin-27 (IL-27) inhibits central nervous system (CNS) inflammation is not clear. In this study we have investigated mechanisms that mitigate or curtail intraocular inflammation (uveitis) and examined whether inhibitory effects of IL-27 are mediated locally by neuroretinal cells or by regulatory T cells. We show here that microglia cells in the neuroretina constitutively secrete IL-27 and its expression is up-regulated during uveitis. We further show that photoreceptors constitutively express IL-27 receptor and respond to IL-27 signalling by producing anti-inflammatory molecules, IL-10 and suppressor of cytokine signalling 1 (SOCS1) through signal transducer and activator of transcription 1 (STAT1) -dependent mechanisms. Moreover, STAT1-deficient mice produced reduced amounts of IL-27, IL-10 and SOCS1 and developed more severe uveitis. Surprisingly, IL-10-producing regulatory T cells had marginal roles in suppressing uveitis. These results suggest that suppression of intraocular inflammation might be mediated through endogenous production of IL-27 and IL-10 by retinal cells, whereas SOCS proteins induced by IL-27 during uveitis may function to protect the neuroretinal cells from the toxic effects of pro-inflammatory cytokines. Targeted delivery of IL-27 into immune privileged tissues of the CNS may therefore be beneficial in the treatment of CNS inflammatory diseases, such as uveitis and multiple sclerosis. C1 [Lee, Yun Sang; Amadi-Obi, Ahjoku; Yu, Cheng-Rong; Egwuagu, Charles E.] NEI, Mol Immunol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Egwuagu, CE (reprint author), NEI, Mol Immunol Sect, Immunol Lab, NIH, Bldg 10,Room 10N116,10 Ctr Dr, Bethesda, MD 20892 USA. EM egwuaguc@nei.nih.gov FU National Eye Institute; US National Institutes of Health FX We thank X. Liu, and R. M. Mahdi (Molecular Immunology Section, National Eye Institute, National Institutes of Health) for their technical assistance. We also thank R. Fariss and J. Tsai (NEI Imaging Core Unit) for assistance with confocal microscopy. This research is funded by Intramural Research Programs of the National Eye Institute and US National Institutes of Health. NR 37 TC 35 Z9 39 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD APR PY 2011 VL 132 IS 4 BP 492 EP 502 DI 10.1111/j.1365-2567.2010.03379.x PG 11 WC Immunology SC Immunology GA 732UV UT WOS:000288216100005 PM 21294722 ER PT J AU Benavente, OR White, CL Pearce, L Pergola, P Roldan, A Benavente, MF Coffey, C McClure, LA Szychowski, JM Conwit, R Heberling, PA Howard, G Bazan, C Vidal-Pergola, G Talbert, R Hart, RG AF Benavente, Oscar R. White, Carole L. Pearce, Lesly Pergola, Pablo Roldan, Ana Benavente, Marie-France Coffey, Christopher McClure, Leslie A. Szychowski, Jeff M. Conwit, Robin Heberling, Patricia A. Howard, George Bazan, Carlos Vidal-Pergola, Gabriela Talbert, Robert Hart, Robert G. CA SPS3 Investigators TI The Secondary Prevention of Small Subcortical Strokes (SPS3) study SO INTERNATIONAL JOURNAL OF STROKE LA English DT Article DE antiplatelet therapy; hypertension; lacunar stroke; randomised clinical trial; SPS3 ID TRANSIENT ISCHEMIC ATTACK; NON-HISPANIC WHITES; HEALTH-CARE PROFESSIONALS; PRESSURE-LOWERING REGIMEN; NORTHERN MANHATTAN STROKE; PLACEBO-CONTROLLED TRIAL; ACUTE CORONARY SYNDROMES; OF-NEUROLOGY-AFFIRMS; SMALL VESSEL DISEASE; HIGH BLOOD-PRESSURE AB Background Small subcortical strokes, also known as lacunar strokes, comprise more than 25% of brain infarcts, and the underlying vasculopathy is the most common cause of vascular cognitive impairment. How to optimally prevent stroke recurrence and cognitive decline in S3 patients is unclear. The aim of the Secondary Prevention of Small Subcortical Strokes study (Trial registration: NCT00059306) is to define strategies for reducing stroke recurrence, cognitive decline, and major vascular events. Methods Secondary Prevention of Small Subcortical Strokes is a randomised, multicentre clinical trial (n=3000) being conducted in seven countries, and sponsored by the US NINDS/NIH. Patients with symptomatic small subcortical strokes in the six-months before and an eligible lesion on magnetic resonance imaging are simultaneously randomised, in a 2 x 2 factorial design, to antiplatelet therapy - 325 mg aspirin daily plus 75 mg clopidogrel daily, vs. 325 mg aspirin daily plus placebo, double-blind - and to one of two levels of systolic blood pressure targets - 'intensive' (< 130 mmHg) vs. 'usual' (130-149 mmHg). Participants are followed for an average of four-years. Time to recurrent stroke (ischaemic or haemorrhagic) is the primary outcome and will be analysed separately for each intervention. The secondary outcomes are the rate of cognitive decline and major vascular events. The primary and most secondary outcomes are adjudicated centrally by those unaware of treatment assignment. Conclusions Secondary Prevention of Small Subcortical Strokes will address several important clinical and scientific questions by testing two interventions in patients with recent magnetic resonance imaging-defined lacunar infarcts, which are likely due to small vessel disease. The results will inform the management of millions of patients with this common vascular disorder. C1 [White, Carole L.] Univ Texas Hlth Sci Ctr San Antonio, SPS3 Coordinating Ctr, Sch Nursing, San Antonio, TX 78229 USA. [Benavente, Oscar R.; Roldan, Ana; Benavente, Marie-France] Univ British Columbia, Dept Med, Div Neurol, Brain Res Ctr, Vancouver, BC V6T 1W5, Canada. [Pearce, Lesly] Bel Air Court, Minot, ND USA. [Pergola, Pablo; Heberling, Patricia A.; Vidal-Pergola, Gabriela; Hart, Robert G.] Univ Texas Hlth Sci Ctr San Antonio, Dept Neurol, San Antonio, TX 78229 USA. [Coffey, Christopher] Univ Iowa, Dept Biostat, Iowa City, IA USA. [McClure, Leslie A.; Szychowski, Jeff M.; Howard, George] Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA. [Conwit, Robin] NINDS, Off Clin Res, Bethesda, MD 20892 USA. [Bazan, Carlos] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Talbert, Robert] Univ Texas Austin, Coll Pharm, Austin, TX 78712 USA. RP Benavente, OR (reprint author), Univ Texas Hlth Sci Ctr San Antonio, SPS3 Coordinating Ctr, Sch Nursing, 8300 Floyd Curl Dr,MSC 7883, San Antonio, TX 78229 USA. EM whitec2@uthscsa.edu RI McClure, Leslie/P-2929-2015 FU National Institute of Neurological Disorders and Stroke of United States [2 U01 NS38529-04A1] FX SPS3 is an investigator initiated study funded by a cooperative agreement from the National Institute of Neurological Disorders and Stroke of United States (Grant #2 U01 NS38529-04A1). Together with members of the SPS3 Executive and Steering Committees, NINDS project officers directly participate in the execution of the study and oversee the progress. The clopidogrel and matching placebo have been donated by Sanofi-Aventis and Bristol-Myers Squibb. Neither company has any involvement with the design, execution, or analysis of the trial. NR 97 TC 65 Z9 68 U1 2 U2 15 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1747-4930 J9 INT J STROKE JI Int. J. Stroke PD APR PY 2011 VL 6 IS 2 BP 164 EP 175 DI 10.1111/j.1747-4949.2010.00573.x PG 12 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 730ES UT WOS:000288016700016 PM 21371282 ER PT J AU Sun, Y Klauzinska, M Lake, RJ Lee, JM Santopietro, S Raafat, A Salomon, D Callahan, R Artavanis-Tsakonas, S AF Sun, Youping Klauzinska, Malgorzata Lake, Robert J. Lee, Joseph M. Santopietro, Stefania Raafat, Ahmed Salomon, David Callahan, Robert Artavanis-Tsakonas, Spyros TI Trp53 regulates Notch 4 signaling through Mdm2 SO JOURNAL OF CELL SCIENCE LA English DT Article DE Trp53; Mdm2; Notch; Ubiquitylation; Tumorigenesis ID MAMMARY EPITHELIAL-CELLS; RING-FINGER DOMAIN; NEOPLASTIC TRANSFORMATION; GLAND DEVELOPMENT; TRANSGENIC MICE; GROWTH-CONTROL; HUMAN HOMOLOG; DNA-DAMAGE; P53; TUMORIGENESIS AB Notch receptors and their ligands have crucial roles in development and tumorigenesis. We present evidence demonstrating the existence of an antagonistic relationship between Notch 4 and Trp53, which is controlled by the Mdm2-dependent ubiquitylation and degradation of the Notch receptor. We show that this signal-controlling mechanism is mediated by physical interactions between Mdm2 and Notch 4 and suggest the existence of a trimeric complex between Trp53, Notch 4 and Mdm2, which ultimately regulates Notch activity. Functional studies indicate that Trp53 can suppress NICD4-induced anchorage-independent growth in mammary epithelial cells and present evidence showing that Trp53 has a pivotal role in the suppression of Notch-associated tumorigenesis in the mammary gland. C1 [Klauzinska, Malgorzata; Lee, Joseph M.; Santopietro, Stefania; Raafat, Ahmed; Salomon, David; Callahan, Robert] NIH, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Sun, Youping; Lake, Robert J.; Artavanis-Tsakonas, Spyros] Harvard Univ, Dept Cell Biol, Boston, MA 02115 USA. [Lake, Robert J.] Univ Penn, Sch Med, Dept Biochem & Biophys, Philadelphia, PA 19104 USA. [Artavanis-Tsakonas, Spyros] Coll France, F-75231 Paris 05, France. [Artavanis-Tsakonas, Spyros] Inst Curie, F-75248 Paris, France. RP Callahan, R (reprint author), NIH, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, Bldg 37,Room 1118A,37 Convent Dr, Bethesda, MD 20892 USA. EM callahro@mail.nih.gov; artavanis@hms.harvard.edu FU National Institutes of Health [NS26084, CA098402]; NIH, National Cancer Institute, Center for Cancer Research FX We thank our colleagues R. A. Obar, A. Mukherjee, K. G. Guruharsha and A. Louvi (Yale University) for their help. We also thank Guillermina Lozano for providing Trp53-null, Mdm2-null MEFs and wild-type MEFs; Bert Vogelstein for supplying HCT116 TP53-null and parental cells; S. Aaronson for crucial reagents and Daiqing Liao for pcDNA3 FLAG-Trp53 expression vectors; Lizi Wu for pcDNA3 HA-NICD1 and pcDNA3 HA-NICD3; and Carl G. Maki for pcDNA3 Mdm2 and pcDNA3 Mdm2 Delta R vectors. This research was supported in part by the National Institutes of Health Grants NS26084 and CA098402 (to S.A.-T.) and partly by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. The authors declare no competing interests. Deposited in PMC for release after 12 months. NR 67 TC 14 Z9 14 U1 0 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD APR 1 PY 2011 VL 124 IS 7 BP 1067 EP 1076 DI 10.1242/jcs.068965 PG 10 WC Cell Biology SC Cell Biology GA 734FC UT WOS:000288318400009 PM 21402876 ER PT J AU Kaneda, K Yamashita, S Woo, S Han, TH AF Kaneda, Kotaro Yamashita, Susumu Woo, Sukyung Han, Tae-Hyung TI Population Pharmacokinetics and Pharmacodynamics of Brief Etomidate Infusion in Healthy Volunteers SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE anesthesia; bispectral index; Observer's Assessment of Alertness and Sedation; plasma etomidate concentration; population pharmacokinetics; pharmacodynamics ID PROPOFOL-INDUCED SEDATION; NITROUS-OXIDE ANESTHESIA; BISPECTRAL INDEX; CONSCIOUSNESS; ALFENTANIL; MIDAZOLAM; MOVEMENT; PERFORMANCE; ISOFLURANE; PREDICTION AB This study established the pharmacokinetic and pharmacodynamic relationships of the bispectral index (BIS) and Observer's Assessment of Alertness/Sedation (OAA/S) scale with effect site drug concentrations during and after brief etomidate infusion. Eighteen American Society of Anesthesiologists status I or II volunteers received etomidate (0.2%) infusion at 5 mg/min until the loss of eyelash reflexes, and spontaneous recovery was allowed. Data for plasma etomidate concentrations, BIS, and OAA/S were collected every minute and analyzed by NONMEM. A 2-compartment pharmacokinetic model and a pharmacodynamic sigmoid E(max) model fit the data best, with volumes of distribution at central and peripheral compartments of 4.45 and 74.90 L, respectively, and systemic and intercompartmental clearances of 0.63 and 3.16 L/min, respectively. t(1/2)k(e0) was 1.550 min. EC(50) values were 0.526 and 0.554 mu g/mL, and gamma values were 2.25 and 6.24 for BIS and OAA/S, respectively. The prediction probability between OAA/S and BIS was 0.8. The slopes of the curves suggest that BIS is a better monitor of depth of sedation and hypnosis, whereas OAA/S may be more useful for monitoring sleep versus wakefulness. These results should be interpreted within the context of short-term etomidate infusion of less than 10 minutes. C1 [Kaneda, Kotaro; Yamashita, Susumu; Han, Tae-Hyung] Univ Iowa Hosp & Clin, Roy J & Lucille A Carver Coll Med, Dept Anesthesia, Iowa City, IA 52242 USA. [Woo, Sukyung] NCI, Clin Pharmacol Program, Bethesda, MD 20892 USA. RP Han, TH (reprint author), Univ Iowa Hosp & Clin, Roy J & Lucille A Carver Coll Med, Dept Anesthesia, 200 Hawkins Dr 6505-3 JCP, Iowa City, IA 52242 USA. EM anthony-han@uiowa.edu NR 32 TC 7 Z9 9 U1 1 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD APR PY 2011 VL 51 IS 4 BP 482 EP 491 DI 10.1177/0091270010369242 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 733JI UT WOS:000288258600003 PM 20498288 ER PT J AU Tamhane, M Gautney, B Shiu, C Segaren, N Jeannis, L Eustache, C Simeon-Fadois, Y Chen, YH De, D Irivinti, S Tamma, P Thompson, CB Khamadi, S Siberry, GK Persaud, D AF Tamhane, M. Gautney, B. Shiu, C. Segaren, N. Jeannis, L. Eustache, C. Simeon-Fadois, Y. Chen, Y. H. De, D. Irivinti, S. Tamma, P. Thompson, C. B. Khamadi, S. Siberry, G. K. Persaud, D. TI Analysis of the optimal cut-point for HIV-p24 antigen testing to diagnose HIV infection in HIV-exposed children from resource-constrained settings SO JOURNAL OF CLINICAL VIROLOGY LA English DT Article DE Human immunodeficiency virus type 1; Dried blood spots (DBS); Paediatrics; Diagnostics; Ultrasensitive p24 antigen assay; Receiver operator characteristics (ROC) ID VIRUS TYPE-1 INFECTION; P24 ANTIGEN; BLOOD SPOTS; ASSAY; INFANTS; PLASMA AB Background: Nucleic-acid-testing (NAT) to diagnose HIV infection in children under age 18 months provides a barrier to HIV-testing in exposed children from resource-constrained settings. The ultrasensitive HIV-p24-antigen (Up24) assay is cheaper and easier to perform and is sensitive (84-98%) and specific (98-100%). The cut-point optical density (OD) selected for discriminating between positive and negative samples may need assessment due to regional differences in mother-to-child HIV-transmission rates. Objectives: We used receiver operator characteristics (ROC) curves and logistic regression analyses to assess the effect of various cut-points on the diagnostic performance of Up24 for HIV-infection status among HIV-exposed children. Positive and negative predictive values at different rates of disease prevalence were also estimated. Study design: A study of Up24 testing on dried blood spot (DBS) samples collected from 278 HIV-exposed Haitian children, 3-24-months of age, in whom HIV-infection status was determined by NAT on the same DBS card. Results: The sensitivity and specificity of Up24 varied by the cut-point-OD value selected. At a cut-point-OD of 8-fold the standard deviation of the negative control (NCSD), sensitivity and specificity of Up24 were maximized [87.8% (95% CI, 83.9-91.6) and 92% (95% CI, 88.8-95.2), respectively]. In lower prevalence settings (5%), positive and negative predictive values of Up24 were maximal (75.9% and 98.8%, respectively) at a cut-point-OD that was 15-fold the NCSD. Conclusions: In low prevalence settings, a high degree of specificity can be achieved with Up24 testing of HIV-exposed children when a higher cut-point OD is used; a feature that may facilitate more frequent use of Up24 antigen testing for HIV-exposed children. (C) 2011 Elsevier B.V. All rights reserved. C1 [Tamhane, M.; Shiu, C.; Chen, Y. H.; Tamma, P.; Persaud, D.] Johns Hopkins Univ, Dept Pediat, Sch Med, Baltimore, MD 21205 USA. [Gautney, B.] Global Hlth Innovat, Kansas City, MO USA. [Thompson, C. B.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Khamadi, S.] Kenya Govt Med Res Ctr, Nairobi, Kenya. [Siberry, G. K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Segaren, N.; Simeon-Fadois, Y.] CARIS Fdn, Colleyville, TX USA. [Jeannis, L.; Eustache, C.] Jhpiego, Port Au Prince, Haiti. RP Persaud, D (reprint author), Johns Hopkins Univ, Dept Pediat, Sch Med, 720 Rutland Ave, Baltimore, MD 21205 USA. EM dpers@jhmi.edu FU ICTR from National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) [UL1 RR 025005]; NIH Roadmap for Medical Research; National Institutes of Health [R01HD057784] FX This work was funded by ICTR award (D.P.) made possible through grant number UL1 RR 025005 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH". The work was also supported by the National Institutes of Health grant # R01HD057784 (D.P.). NR 20 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD APR PY 2011 VL 50 IS 4 BP 338 EP 341 DI 10.1016/j.jcv.2011.01.012 PG 4 WC Virology SC Virology GA 733EK UT WOS:000288244900015 PM 21330193 ER PT J AU Nikitina, ER Mikhailov, AV Nikandrova, ES Frolova, EV Fadeev, AV Shman, VV Shilova, VY Tapilskaya, NI Shapiro, JI Fedorova, OV Bagrov, AY AF Nikitina, Elena R. Mikhailov, Anton V. Nikandrova, Ekaterina S. Frolova, Elena V. Fadeev, Artem V. Shman, Vera V. Shilova, Victoria Y. Tapilskaya, Natalia I. Shapiro, Joseph I. Fedorova, Olga V. Bagrov, Alexei Y. TI In preeclampsia endogenous cardiotonic steroids induce vascular fibrosis and impair relaxation of umbilical arteries SO JOURNAL OF HYPERTENSION LA English DT Article DE collagen; digitalis-like factor; endothelium-independent vasorelaxation; fibrosis; Fli-1; marinobufagenin; Na/K-ATPase; preeclampsia; umbilical arteries ID EXPERIMENTAL UREMIC CARDIOMYOPATHY; LOWERS BLOOD-PRESSURE; ATPASE INHIBITION; IMMUNOREACTIVE SUBSTANCE; MARINOBUFAGENIN; PREGNANCIES; STIFFNESS; IMMUNOGLOBULIN; PATHOGENESIS; EXPRESSION AB Background Marinobufagenin (MBG), a bufadienolide cardiotonic steroid, induces cardiovascular fibrosis. Because levels of MBG in preeclampsia are increased, and anti-MBG monoclonal antibody reduces blood pressure (BP) in a rat model of preeclampsia, we hypothesized that in preeclampsia, elevated MBG levels would be associated with the development of fibrosis in feto-placental circulation and with impairment of vascular relaxation. Method We studied 16 patients with preeclampsia (systolic BP=150 +/- 4 mmHg; 28 +/- 2 years, 37 +/- 1 weeks gestational age) and 14 gestational age-matched normal pregnant women (systolic BP=112 +/- 2 mmHg). Results Preeclampsia was associated with a rise in plasma and placental levels of MBG. In preeclamptic umbilical arteries, the expression of Fli-1, a transcription factor and a negative regulator of fibrosis, was significantly reduced (P < 0.001), whereas procollagen-1 expression was increased (P < 0.01). As compared to control vessels, isolated rings of umbilical arteries from patients with preeclampsia demonstrated unaltered responsiveness to endothelin-1 (EC(50)=2.2 and 3.2 nmol/l, respectively), but exhibited an impaired response to the relaxant effect of sodium nitroprusside (EC(50)=1.5 vs. 32.4 nmol/l, P <.001) following endothelin-1-induced constriction. Ex-vivo treatment of normal umbilical arteries explants with 1 and 10 nmol/l MBG for 24 h mimicked the effects of preeclampsia, specifically suppressed Fli-1 and increased collagen-1 expression while impairing vasorelaxation. Conclusion Our results indicate that in preeclampsia, elevated levels of MBG induce vascular fibrosis via a Fli-1-dependent mechanism which leads to an impairment of vasorelaxation, and suggest that MBG represents a potential target for therapy of this syndrome. J Hypertens 29:769-776 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Shilova, Victoria Y.; Fedorova, Olga V.; Bagrov, Alexei Y.] NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. [Nikitina, Elena R.; Frolova, Elena V.; Fadeev, Artem V.] Russian Acad Sci, Sechenov Inst Evolutionary Physiol & Biochem, St Petersburg 196140, Russia. [Mikhailov, Anton V.; Nikandrova, Ekaterina S.; Shman, Vera V.] St Petersburg State Univ, Fac Med, St Petersburg, Russia. [Mikhailov, Anton V.; Nikandrova, Ekaterina S.; Shman, Vera V.] Matern Hosp, St Petersburg, Russia. [Shapiro, Joseph I.] Univ Toledo, Dept Med, Toledo, OH USA. [Tapilskaya, Natalia I.] Sch Pediat Med, Dept Obstet & Gynecol, St Petersburg, Russia. RP Bagrov, AY (reprint author), NIA, Cardiovasc Sci Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM BagrovA@mail.nih.gov FU National Institute on Aging, National Institutes of Health FX Supported by Intramural Research Program, National Institute on Aging, National Institutes of Health (A.Y.B., O.V.F., V.Y.S.). NR 33 TC 11 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD APR PY 2011 VL 29 IS 4 BP 769 EP 776 DI 10.1097/HJH.0b013e32834436a7 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 732PH UT WOS:000288199500022 PM 21330936 ER PT J AU Chen, Q Reis, SE Kammerer, C Craig, W McNamara, DM Holubkov, R Sharaf, BL Sopko, G Pauly, DF Merz, CNB Kamboh, MI AF Chen, Qi Reis, Steven E. Kammerer, Candace Craig, Wendy McNamara, Dennis M. Holubkov, Richard Sharaf, Barry L. Sopko, George Pauly, Daniel F. Merz, C. Noel Bairey Kamboh, M. Ilyas CA WISE Study Grp TI Association of anti-oxidized LDL and candidate genes with severity of coronary stenosis in the Women's Ischemia Syndrome Evaluation study SO JOURNAL OF LIPID RESEARCH LA English DT Article DE anti-oxLDL antibodies; genetics; low density lipoprotein ID LOW-DENSITY-LIPOPROTEIN; SYNDROME EVALUATION WISE; INTIMA-MEDIA THICKNESS; HEPATIC LIPASE GENE; ARTERY-DISEASE; CHOLESTEROL LEVELS; MYOCARDIAL-INFARCTION; HEALTHY POPULATION; APOE POLYMORPHISM; IMMUNE-COMPLEXES AB Atherosclerosis is the major cause of coronary artery disease (CAD), and oxidized LDL (oxLDL) is believed to play a key role in the initiation of the atherosclerotic process. Recent studies show that inflammation and autoimmune reactions are also relevant in atherosclerosis. In this study, we examined the association of antibodies against oxLDL (anti-oxLDL) with the severity of CAD in 558 Women's Ischemia Syndrome Evaluation (WISE) study samples (465 whites; 93 blacks) determined by coronary stenosis (<20%, 20%-49%, >50% stenosis). We also examined the relationship of anti-oxLDL with serum lipid levels and nine candidate genes including APOE, APOH, APOA5, LPL, LRP1, HL, CETP, PON1, and OLR1. IgM anti-oxLDL levels were significantly higher in the >20% stenosis group than in the boolean AND 20% stenosis group in whites (0.69 +/- 0.02 vs. 0.64 +/- 0.01, respectively; P = 0.02). IgM anti-oxLDL levels correlated significantly with total cholesterol (r(2) = 0.01; P = 0.03) and LDL cholesterol (r(2) = 0.017; P = 0.004) in whites. Multiple regression analysis revealed a suggestive association of LPL/S447X single-nucleotide polymorphism (SNP) with both IgG anti-oxLDL (P = 0.02) and IgM anti-oxLDL (P = 0.07), as well as between IgM anti-oxLDL and the OLR1/3'UTR SNP (P = 0.020).jlr Our data suggest that higher IgM anti-oxLDL levels may provide protection against coronary stenosis and that genetic variation in some candidate genes are determinants of anti-oxLDL levels.-Chen, Q., S. E. Reis, C. Kammerer, W. Craig, D. M. McNamara, R. Holubkov, B. L. Sharaf, G. Sopko, D. F. Pauly, C. N. B. Merz, and M. Ilyas Kamboh for the WISE study group. Association of anti-oxidized LDL and candidate genes with severity of coronary stenosis in the WISE study. J. Lipid Res. 2011. 52: 801-807. C1 [Chen, Qi; Kammerer, Candace; Kamboh, M. Ilyas] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA 15260 USA. [Reis, Steven E.; McNamara, Dennis M.] Univ Pittsburgh, Sch Med, Dept Med, Cardiovasc Inst, Pittsburgh, PA USA. [Craig, Wendy] Fdn Blood Res, Scarborough, ME 04074 USA. [Holubkov, Richard] Univ Utah, Sch Med, Dept Pediat, Intermt Injury Control Res Ctr, Salt Lake City, UT USA. [Sharaf, Barry L.] Rhode Isl Hosp, Div Cardiol, Providence, RI USA. [Sopko, George] NHLBI, Div Heart & Vasc Dis, Bethesda, MD 20892 USA. [Pauly, Daniel F.] Univ Florida, Div Cardiol, Gainesville, FL USA. [Merz, C. Noel Bairey] Cedars Sinai Heart Inst, Los Angeles, CA USA. RP Kamboh, MI (reprint author), Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA 15260 USA. EM kamboh@pitt.edu RI Reis, Steven/J-3957-2014; OI Kamboh, M. Ilyas/0000-0002-3453-1438 FU National Heart, Lung and Blood Institutes [R01-HL-54900, R01-HL112883, R01-HL115215, N01-HV-68161, N01-HV-68162, N01-HV-68163, N01-HV-68164]; National Center for Research Resources [MO1-RR-00425]; Gustavus and Louis Pfeiffer Research Foundation, Denville, NJ; Ladies Hospital Aid Society of Western Pennsylvania, Pittsburgh, PA; Women's Guild of Cedars-Sinai Medical Center; Edythe L. Broad Women's Heart Research Endowment; Cedars-Sinai Medical Center; Cedars-Sinai Medical Center, Los Angeles, CA FX This work was supported by National Heart, Lung and Blood Institutes contracts R01-HL-54900, R01-HL112883, R01-HL115215, N01-HV-68161, N01-HV-68162, N01-HV-68163, and N01-HV-68164; by GCRC Grant MO1-RR-00425 from the National Center for Research Resources; and by grants from the Gustavus and Louis Pfeiffer Research Foundation, Denville, NJ; the Ladies Hospital Aid Society of Western Pennsylvania, Pittsburgh, PA; and the Women's Guild of Cedars-Sinai Medical Center, the Edythe L. Broad Women's Heart Research Endowment, Cedars-Sinai Medical Center, and the Barbra Streisand Women's Heart Disease Research and Education Program, Cedars-Sinai Medical Center, Los Angeles, CA. NR 59 TC 16 Z9 16 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD APR PY 2011 VL 52 IS 4 BP 801 EP 807 DI 10.1194/jlr.M012963 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 733CX UT WOS:000288239300019 PM 21252261 ER PT J AU Lee, SM Yoon, BH Romero, R AF Lee, Seung Mi Yoon, Bo Hyun Romero, Roberto TI Comment and reply on: The clinical significance of a positive Amnisure test in women with term labor with intact membranes Reply SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Letter ID CESAREAN DELIVERY; RISK C1 [Lee, Seung Mi; Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South Korea. [Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. RP Yoon, BH (reprint author), Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South Korea. EM yoonbh@snu.ac.kr NR 5 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PD APR PY 2011 VL 24 IS 4 BP 654 EP 656 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 730GI UT WOS:000288021400024 ER PT J AU Avital, I AF Avital, Itzhak TI Response to the Article "Pulmonary Resection for Metastatic Gastric Cancer" by Kemp et al. In Response SO JOURNAL OF THORACIC ONCOLOGY LA English DT Letter C1 NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Avital, I (reprint author), NCI, Surg Branch, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA. EM avitali@mail.nih.gov NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD APR PY 2011 VL 6 IS 4 BP 836 EP 837 DI 10.1097/JTO.0b013e318213a8d0 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 732AX UT WOS:000288155100032 ER PT J AU Colt, JS Karagas, MR Schwenn, M Baris, D Johnson, A Stewart, P Verrill, C Moore, LE Lubin, J Ward, MH Samanic, C Rothman, N Cantor, KP Freeman, LEB Schned, A Cherala, S Silverman, DT AF Colt, Joanne S. Karagas, Margaret R. Schwenn, Molly Baris, Dalsu Johnson, Alison Stewart, Patricia Verrill, Castine Moore, Lee E. Lubin, Jay Ward, Mary H. Samanic, Claudine Rothman, Nathaniel Cantor, Kenneth P. Freeman, Laura E. Beane Schned, Alan Cherala, Sai Silverman, Debra T. TI Occupation and bladder cancer in a population-based case-control study in Northern New England SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; LOWER URINARY-TRACT; RURAL NEW-ENGLAND; METALWORKING FLUIDS; UNITED-STATES; RISK-FACTORS; MORTALITY; EXPOSURE; MEN; WORKERS AB Objectives We used data from a large, population-based case-control study in Maine, New Hampshire, and Vermont to examine relationships between occupation, industry and bladder cancer risk. Methods Lifetime occupational histories were obtained by personal interview from 1158 patients newly diagnosed with urothelial carcinoma of the bladder in 2001-2004, and from 1402 population controls. Unconditional logistic regression was used to calculate ORs and 95% CIs, adjusted for demographic factors, smoking and employment in other high-risk occupations. Results Male precision metalworkers and metalworking/plasticworking machine operators had significantly elevated risks and significant trends in risk with duration of employment (precision metalworkers: OR 2.2, 95% CI 1.4 to 3.4, p(trend)=0.0065; metalworking/plasticworking machine operators: OR 1.6, 95% CI 1.01 to 2.6, p(trend)=0.047). Other occupations/industries for which risk increased significantly with duration of employment included: for men, textile machine operators, mechanics/repairers, automobile mechanics, plumbers, computer systems analysts, information clerks, and landscape industry workers; for women, service occupations, health services, cleaning and building services, managementrelated occupations, electronic components manufacturing and transportation equipment manufacturing. Men reporting use of metalworking fluids (MWF) had a significantly elevated bladder cancer risk (OR 1.7, 95% CI 1.1 to 2.5). Conclusions Our findings support the hypothesis that some component(s) of MWF may be carcinogenic to the bladder. Our results also corroborate many other previously reported associations between bladder cancer risk and various occupations. More detailed analyses using information from the study's job-specific questionnaires may help to identify MWF components that may be carcinogenic, and other bladder carcinogens associated with a variety of occupations. C1 [Colt, Joanne S.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv,Occupat & Environm Epidemi, Bethesda, MD 20892 USA. [Karagas, Margaret R.; Schned, Alan] Dartmouth Med Sch, Lebanon, NH USA. [Schwenn, Molly; Verrill, Castine] Maine Canc Registry, Augusta, ME USA. [Johnson, Alison] Vermont Canc Registry, Burlington, VT USA. [Stewart, Patricia] Stewart Exposure Assessments LLC, Arlington, VA USA. [Cantor, Kenneth P.] KP Cantor Environm LLC, Silver Spring, MD USA. [Cherala, Sai] New Hampshire Dept Hlth & Human Serv, Concord, NH 03301 USA. RP Colt, JS (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv,Occupat & Environm Epidemi, 6120 Execut Blvd,Room 8002, Bethesda, MD 20892 USA. EM coltj@mail.nih.gov RI Beane Freeman, Laura/C-4468-2015 OI Beane Freeman, Laura/0000-0003-1294-4124 FU NIH FX The NIH funded this study. NR 61 TC 22 Z9 22 U1 3 U2 12 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD APR PY 2011 VL 68 IS 4 BP 239 EP 249 DI 10.1136/oem.2009.052571 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 732DO UT WOS:000288164700003 PM 20864470 ER PT J AU Kolb, EA Gorlick, R Lock, R Carol, H Morton, CL Keir, ST Reynolds, CP Kang, MH Mans, JM Billups, C Smith, MA Houghton, PJ AF Kolb, E. Anders Gorlick, Richard Lock, Richard Carol, Hernan Morton, Christopher L. Keir, Stephen T. Reynolds, C. Patrick Kang, Min H. Mans, John M. Billups, Catherine Smith, Malcolm A. Houghton, Peter J. TI Initial Testing (Stage 1) of the IGF-1 Receptor Inhibitor BMS-754807 by the Pediatric Preclinical Testing Program SO PEDIATRIC BLOOD & CANCER LA English DT Article DE developmental therapeutics; IGF-1 receptor inhibitor; preclinical testing ID GROWTH-FACTOR-I; ACUTE LYMPHOBLASTIC-LEUKEMIA; BREAST-CANCER CELLS; EWINGS-SARCOMA; OSTEOSARCOMA CELLS; XENOGRAFT MODELS; ANTIBODY IMC-A12; INSULIN; EXPRESSION; PROLIFERATION AB Background. BMS-754807 is a small molecule ATP-competitive inhibitor of the type-1 insulin-like growth factor receptor currently in phase 1 clinical trials. Procedures. BMS-754807 was tested against the Pediatric Preclinical Testing Program (PPTP) in vitro panel at concentrations ranging from 1.0 nM to 10 mu M and was tested against the PPTP in vivo panels at a dose of 25 mg/kg administered orally BID for 6 days, repeated for 6 weeks. Results. In vitro BMS-754807 showed a median EC(50) value of 0.62 mu M against the PPTP cell lines. The median EC(50) for the four Ewing sarcoma cell lines was less than that for the remaining PPTP cell lines (0.19 mu M vs. 0.78 mu M, P=0.0470). In vivo BMS-754807 induced significant differences in EFS distribution compared to controls in 18 of 32 evaluable solid tumor xenografts (56%) tested, but in none of the ALL xenografts studied. Criteria for intermediate activity for the time to event activity measure (EFS T/C > 2) were met in 7 of 27 solid tumor xenografts 'evaluable for this measure. The best response was PD2 (progressive disease with growth delay), which was observed in 18 of 32 solid tumor xenografts. PD2 responses were most commonly observed in the rhabdomyosarcoma, neuroblastoma, osteosarcoma, Ewing sarcoma, and Wilms tumor panels. Conclusions. BMS-754807 activity in vitro is consistent with a specific IGF-1R effect that has half-maximal response in the 0.1 mu M range and that is observed in a minority of the PPTP cell lines. In vivo intermediate activity was most commonly observed in the neuroblastoma and rhabdomyosarcoma panels. Pediatr Blood Cancer. 2011;56:595-603. (C) 2010 Wiley-Liss, Inc. C1 [Kolb, E. Anders] Alfred I DuPont Hosp Children, Nemours Ctr Childhood Canc Res, Wilmington, DE USA. [Gorlick, Richard] Childrens Hosp Montefiore, Bronx, NY USA. [Lock, Richard; Carol, Hernan] Childrens Canc Inst Australia Med Res, Randwick, NSW, Australia. [Morton, Christopher L.; Billups, Catherine] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Keir, Stephen T.] Duke Univ, Med Ctr, Durham, NC USA. [Reynolds, C. Patrick; Kang, Min H.] Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA. [Mans, John M.] Univ Penn, Sch Med, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Mans, John M.] Abramson Family Canc Res Inst, Philadelphia, PA USA. [Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Houghton, Peter J.] Nationwide Childrens Hosp, Columbus, OH USA. RP Kolb, EA (reprint author), Alfred I DuPont Hosp Children, Nemours Ctr Childhood Canc Res, Wilmington, DE USA. EM eakolb@nemours.org RI Houghton, Peter/E-3265-2011; Carol, Hernan/F-5750-2013; Lock, Richard/G-4253-2013; OI Carol, Hernan/0000-0002-9443-8032; Reynolds, C. Patrick/0000-0002-2827-8536 FU National Cancer Institute [NO1-CM-42216, CA21765, CA108786] FX Grant sponsor: National Cancer Institute; Grant numbers: NO1-CM-42216, CA21765, CA108786. NR 44 TC 36 Z9 37 U1 0 U2 1 PU WILEY PERIODICALS, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD APR PY 2011 VL 56 IS 4 BP 595 EP 603 DI 10.1002/pbc.22741 PG 9 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 729XD UT WOS:000287986700015 PM 21298745 ER PT J AU Bauer, J Buttner, P Murali, R Okamoto, I Kolaitis, NA Landi, MT Scolyer, RA Bastian, BC AF Bauer, Juergen Buettner, Petra Murali, Rajmohan Okamoto, Ichiro Kolaitis, Nicholas A. Landi, Maria T. Scolyer, Richard A. Bastian, Boris C. TI BRAF mutations in cutaneous melanoma are independently associated with age, anatomic site of the primary tumor, and the degree of solar elastosis at the primary tumor site SO PIGMENT CELL & MELANOMA RESEARCH LA English DT Article DE BRAF; genetics; melanoma; mutation; pathology; solar elastosis; ultraviolet exposure ID MALIGNANT-MELANOMA; MELANOCYTIC NEVI; MUTANT MELANOMA; SUN EXPOSURE; RISK; FEATURES; GENE; NRAS AB P>Oncogenic BRAF mutations are more frequent in cutaneous melanoma occurring at sites with little or moderate sun-induced damage than at sites with severe cumulative solar ultraviolet (UV) damage. We studied cutaneous melanomas from geographic regions with different levels of ambient UV radiation to delineate the relative effects of cumulative UV damage, age, and anatomic site on the frequency of BRAF mutations. We show that BRAF-mutated melanomas occur in a younger age group on skin without marked solar elastosis and less frequently affect the head and neck area, compared to melanomas without BRAF mutations. The findings indicate that BRAF-mutated melanomas arise early in life at low cumulative UV doses, whereas melanomas without BRAF mutations require accumulation of high UV doses over time. The effect of anatomic site on the mutation spectrum further suggests regional differences among cutaneous melanocytes. C1 [Bauer, Juergen; Kolaitis, Nicholas A.; Bastian, Boris C.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Bauer, Juergen] Univ Tubingen, Dept Dermatol, Tubingen, Germany. [Buettner, Petra] James Cook Univ, Sch Publ Hlth Trop Med & Rehabil Sci, Townsville, Qld, Australia. [Murali, Rajmohan; Scolyer, Richard A.] Univ Sydney, Melanoma Inst Australia, Royal Prince Alfred Hosp, Sydney Med Sch, Sydney, NSW 2006, Australia. [Okamoto, Ichiro] Univ Vienna, Sch Med, Dept Dermatol, Vienna, Austria. [Landi, Maria T.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Bastian, Boris C.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA. [Bastian, Boris C.] Univ Calif San Francisco, UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. RP Bastian, BC (reprint author), Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. EM bastianb@mskcc.org RI MURALI, RAJMOHAN/A-7960-2008; Bauer, Jurgen/B-4656-2008; OI MURALI, RAJMOHAN/0000-0001-6988-4295; Kolaitis, Nicholas/0000-0002-4586-959X; Bauer, Jurgen/0000-0001-8789-1536; Scolyer, Richard/0000-0002-8991-0013 FU Melanoma Research Foundation; National Cancer Institute [R01 CA1315241]; Intendis Austria; Osterreichische Nationalbank [13036] FX Supported by a Melanoma Research Foundation Established Investigator Award and the National Cancer Institute (R01 CA1315241) to Dr. Bastian. Dr. Okamoto is supported by Intendis Austria and the Osterreichische Nationalbank (project number 13036). Dr. Scolyer is a Cancer Institute New South Wales Clinical Research Fellow. NR 26 TC 89 Z9 92 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1755-1471 J9 PIGM CELL MELANOMA R JI Pigment Cell Melanoma Res. PD APR PY 2011 VL 24 IS 2 BP 345 EP 351 DI 10.1111/j.1755-148X.2011.00837.x PG 7 WC Oncology; Cell Biology; Dermatology SC Oncology; Cell Biology; Dermatology GA 732WA UT WOS:000288219200013 PM 21324100 ER PT J AU Zaidi, MR Hornyak, TJ Merlino, G AF Zaidi, M. Raza Hornyak, Thomas J. Merlino, Glenn TI A genetically engineered mouse model with inducible GFP expression in melanocytes SO PIGMENT CELL & MELANOMA RESEARCH LA English DT Editorial Material ID MELANOMAGENESIS; SKIN C1 [Zaidi, M. Raza; Hornyak, Thomas J.; Merlino, Glenn] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Zaidi, MR (reprint author), NCI, Ctr Canc Res, NIH, 37 Convent Dr,Room 5002, Bethesda, MD 20892 USA. EM zaidir@mail.nih.gov; merlinog@mail.nih.gov RI Zaidi, M. Raza/H-1386-2016 OI Zaidi, M. Raza/0000-0003-0480-3188 NR 8 TC 5 Z9 5 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-1471 J9 PIGM CELL MELANOMA R JI Pigment Cell Melanoma Res. PD APR PY 2011 VL 24 IS 2 BP 393 EP 394 DI 10.1111/j.1755-148X.2011.00832.x PG 2 WC Oncology; Cell Biology; Dermatology SC Oncology; Cell Biology; Dermatology GA 732WA UT WOS:000288219200022 PM 21392368 ER PT J AU Hoenerhoff, MJ Shibata, MA Bode, A Green, JE AF Hoenerhoff, M. J. Shibata, M. A. Bode, A. Green, J. E. TI Pathologic progression of mammary carcinomas in a C3(1)/SV40 T/t-antigen transgenic rat model of human triple-negative and Her2-positive breast cancer SO TRANSGENIC RESEARCH LA English DT Article DE Breast cancer; C3(1)/SV40 T/t-antigen; C3(1)/Tag; Transgenic rat; Basal-type breast cancer; Triple-negative breast cancer ID GENE-EXPRESSION PATTERNS; LARGE-TUMOR-ANTIGEN; BASAL-LIKE SUBTYPE; T-ANTIGEN; EPITHELIAL-CELLS; MOUSE MODEL; PROSTATE; MICE; CARCINOGENESIS; PHENOTYPE AB The C3(1) component of the rat prostate steroid binding protein has been used to target expression of the SV40 T/t-antigen to the mammary epithelium of mice resulting in pre-neoplastic lesions that progress to invasive and metastatic cancer with molecular features of human basal-type breast cancer. However, there are major differences in the histologic architecture of the stromal and epithelial elements between the mouse and human mammary glands. The rat mammary gland is more enriched with epithelial and stromal components than the mouse and more closely resembles the cellular composition of the human gland. Additionally, existing rat models of mammary cancer are typically estrogen receptor positive and hormone responsive, unlike most genetically engineered mouse mammary cancer models. In an attempt to develop a mammary cancer model that might more closely resemble the pathology of human breast cancer, we generated a novel C3(1)/SV40 T/t-antigen transgenic rat model that developed progressive mammary lesions leading to highly invasive adenocarcinomas. However, aggressive tumor development prevented the establishment of transgenic lines. Characterization of the tumors revealed that they were primarily estrogen receptor and progesterone receptor negative, and either her2/neu positive or negative, resembling human triple-negative or Her2 positive breast cancer. Tumors expressed the basal marker K14, as well as the luminal marker K18, and were negative for smooth muscle actin. The triple negative phenotype has not been previously reported in a rat mammary cancer model. Further development of a C3(1)SV40 T/t-antigen based model could establish valuable transgenic rat lines that develop basal-type mammary tumors. C1 [Hoenerhoff, M. J.; Green, J. E.] NCI, Transgen Oncogenesis & Genom Sect, Lab Canc Biol & Genet, NIH, Res Triangle Pk, NC 27709 USA. [Bode, A.] Univ Minnesota, Hormel Inst, Carcinogenesis & Chemoprevent Program, Austin, MN 55912 USA. RP Green, JE (reprint author), NCI, Transgen Oncogenesis & Genom Sect, Lab Canc Biol & Genet, NIH, 37 Convent Dr,Bldg 37,Room 4054, Res Triangle Pk, NC 27709 USA. EM jegreen@nih.gov FU NIH, National Cancer Institute FX This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute. We are grateful to Ron Lubet (NCI) and Clinton Grubbs (University of Alabama-Birmingham) for their assistance in providing control samples for immunohistochemistry, and Donna Bucher at PHL (NCI-Frederick) for technical assistance. We would like to thank Jerry Ward (Global Vet Pathology) for helpful discussions. NR 56 TC 5 Z9 5 U1 0 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-8819 EI 1573-9368 J9 TRANSGENIC RES JI Transgenic Res. PD APR PY 2011 VL 20 IS 2 BP 247 EP 259 DI 10.1007/s11248-010-9406-5 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 732GB UT WOS:000288171900003 PM 20549348 ER PT J AU Chefer, V Meis, J Wang, G Kuzmin, A Bakalkin, G Shippenberg, T AF Chefer, Vladimir Meis, Jennifer Wang, Grace Kuzmin, Alexander Bakalkin, Georgy Shippenberg, Toni TI Repeated exposure to moderate doses of ethanol augments hippocampal glutamate neurotransmission by increasing release SO ADDICTION BIOLOGY LA English DT Article DE Ethanol; GABA; glutamate; hippocampus; microdialysis; rat ID RECEPTOR IONOPHORE COMPLEX; EXCITATORY AMINO-ACIDS; IN-VIVO MICRODIALYSIS; NMDA RECEPTOR; RAT-BRAIN; EXTRACELLULAR GLUTAMATE; NUCLEUS-ACCUMBENS; BINGE DRINKING; WITHDRAWAL; MECHANISMS AB The present study used conventional and quantitative microdialysis to assess glutamatergic and GABAergic neurotransmission in the hippocampal CA3 area of the rat following a moderate-dose ethanol treatment regimen. Male Wistar rats received 3.4 g/kg of ethanol or water for 6 days via gastric gavage. Microdialysis experiments commenced 2 days later. Basal and depolarization-induced glutamate overflow were significantly elevated in ethanol-treated animals. Basal and depolarization-induced gamma-aminobutyric acid (GABA) overflow were unaltered. Quantitative no-net-flux microdialysis was used to determine if changes in dialysate glutamate levels following ethanol administration are due to an increase in release or a decrease in uptake. To confirm the validity of this method for quantifying basal glutamate dynamics, extracellular concentrations of glutamate and the extraction fraction, which reflects changes in analyte clearance, were quantified in response to retro-dialysis of the glutamate uptake blocker trans-pyrrolidine-2,4-dicarboxylic acid (tPDC). tPDC significantly decreased the extraction fraction for glutamate, resulting in augmented extracellular glutamate concentrations. Repeated ethanol administration did not alter the glutamate extraction fraction. However, extracellular glutamate concentrations were significantly elevated, indicating that glutamate release is increased as a consequence of repeated ethanol administration. These data demonstrate that repeated bouts of moderate ethanol consumption alter basal glutamate dynamics in the CA3 region of the dorsal hippocampus. Basal glutamate release is augmented, whereas glutamate uptake is unchanged. Furthermore, they suggest that dysregulation of glutamate transmission in this region may contribute to the previously documented deficits in cognitive function associated with moderate dose ethanol use. C1 [Chefer, Vladimir] NIDA, Integrat Neurosci Sect, Integrat Neurosci Branch, IRP,NIH, Baltimore, MD 21224 USA. [Kuzmin, Alexander; Bakalkin, Georgy] Uppsala Univ, Div Biol Res Drug Dependence, Dept Pharmaceut Biosci, Uppsala, Sweden. RP Chefer, V (reprint author), NIDA, Integrat Neurosci Sect, Integrat Neurosci Branch, IRP,NIH, 333 Cassell Dr, Baltimore, MD 21224 USA. EM vchefer@intra.nida.nih.gov OI Bakalkin, Georgy/0000-0002-8074-9833 FU National Institute on Drug Abuse/Intramural Research Program (NIDA/IRP); Swedish Council for Working Life and Social Research (FAS); AFA Forsakring; Swedish Science Research Council; Alcohol Research Council of the Swedish Retailing Monopoly; Uppsala University; Karolinska Institutet FX This work was supported by the National Institute on Drug Abuse/Intramural Research Program (NIDA/IRP) and grants from the Swedish Council for Working Life and Social Research (FAS), AFA Forsakring, Swedish Science Research Council, Alcohol Research Council of the Swedish Retailing Monopoly, and funds from Uppsala University and Karolinska Institutet. NR 54 TC 24 Z9 24 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1355-6215 J9 ADDICT BIOL JI Addict. Biol. PD APR PY 2011 VL 16 IS 2 BP 229 EP 237 DI 10.1111/j.1369-1600.2010.00272.x PG 9 WC Biochemistry & Molecular Biology; Substance Abuse SC Biochemistry & Molecular Biology; Substance Abuse GA 730HQ UT WOS:000288024800005 PM 21182572 ER PT J AU Airavaara, M Pickens, CL Stern, AL Wihbey, KA Harvey, BK Bossert, JM Liu, QR Hoffer, BJ Shaham, Y AF Airavaara, Mikko Pickens, Charles L. Stern, Anna L. Wihbey, Kristina A. Harvey, Brandon K. Bossert, Jennifer M. Liu, Qing-Rong Hoffer, Barry J. Shaham, Yavin TI Endogenous GDNF in ventral tegmental area and nucleus accumbens does not play a role in the incubation of heroin craving SO ADDICTION BIOLOGY LA English DT Article DE CDNF; craving; drug self-administration; extinction; GDNF; incubation; MANF; neurotrophic factors; nucleus accumbens; reinstatement; relapse; ventral tegmental area ID MESOLIMBIC DOPAMINE SYSTEM; INDUCED COCAINE SEEKING; CONTEXT-INDUCED RELAPSE; NEURONS IN-VIVO; NEUROTROPHIC FACTOR; DRUG-SEEKING; WITHDRAWAL PERIODS; SIGNALING PATHWAY; SUBSTANTIA-NIGRA; PROTEIN-LEVELS AB Glial cell line-derived neurotrophic factor (GDNF) activity in ventral tegmental area (VTA) mediates the time-dependent increases in cue-induced cocaine-seeking after withdrawal (incubation of cocaine craving). Here, we studied the generality of these findings to incubation of heroin craving. Rats were trained to self-administer heroin for 10 days (6 hours/day; 0.075 mg/kg/infusion; infusions were paired with a tone-light cue) and tested for cue-induced heroin-seeking in extinction tests after 1, 11 or 30 withdrawal days. Cue-induced heroin seeking was higher after 11 or 30 days than after 1 day (incubation of heroin craving), and the time-dependent increases in extinction responding were associated with time-dependent changes in GDNF mRNA expression in VTA and nucleus accumbens. Additionally, acute accumbens (but not VTA) GDNF injections (12.5 mu g/side) administered 1-3 hours after the last heroin self-administration training session enhanced the time-dependent increases in extinction responding after withdrawal. However, the time-dependent increases in extinction responding after withdrawal were not associated with changes in GDNF protein expression in VTA and accumbens. Additionally, interfering with endogenous GDNF function by chronic delivery of anti-GDNF monoclonal neutralizing antibodies (600 ng/side/day) into VTA or accumbens had no effect on the time-dependent increases in extinction responding. In summary, heroin self-administration and withdrawal regulate VTA and accumbens GDNF mRNA expression in a time-dependent manner, and exogenous GDNF administration into accumbens but not VTA potentiates cue-induced heroin seeking. However, based on the GDNF protein expression and the anti-GDNF monoclonal neutralizing antibodies manipulation data, we conclude that neither accumbens nor VTA endogenous GDNF mediates the incubation of heroin craving. C1 [Shaham, Yavin] NIDA, Behav Neurosci Branch, IRP, NIH, Baltimore, MD 21224 USA. RP Shaham, Y (reprint author), NIDA, Behav Neurosci Branch, IRP, NIH, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA. EM yshaham@intra.nida.nih.gov RI shaham, yavin/G-1306-2014; Liu, Qing-Rong/A-3059-2012; OI Liu, Qing-Rong/0000-0001-8477-6452; Airavaara, Mikko/0000-0002-2026-1609 FU National Institute on Drug Abuse (NIH, DHHS) FX This work was supported by the Intramural Research Program of the National Institute on Drug Abuse (NIH, DHHS). The authors declare that they do not have any conflicts of interest (financial or otherwise) related to the data presented in this manuscript. We thank S. Golden, Dr F. Theberge and Dr B. Hope for their help in conducting the experiments, and Drs AC. Granholm and D. Ron for their help with the GDNF Western blot assay. NR 67 TC 22 Z9 23 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1355-6215 J9 ADDICT BIOL JI Addict. Biol. PD APR PY 2011 VL 16 IS 2 BP 261 EP 272 DI 10.1111/j.1369-1600.2010.00281.x PG 12 WC Biochemistry & Molecular Biology; Substance Abuse SC Biochemistry & Molecular Biology; Substance Abuse GA 730HQ UT WOS:000288024800008 PM 21182575 ER PT J AU Dearfield, KL Thybaud, V Cimino, MC Custer, L Czich, A Harvey, JS Hester, S Kim, JH Kirkland, D Levy, DD Lorge, E Moore, MM Ouedraogo-Arras, G Schuler, M Suter, W Sweder, K Tarlo, K van Benthem, J van Goethem, F Witt, KL AF Dearfield, Kerry L. Thybaud, Veronique Cimino, Michael C. Custer, Laura Czich, Andreas Harvey, James S. Hester, Susan Kim, James H. Kirkland, David Levy, Dan D. Lorge, Elisabeth Moore, Martha M. Ouedraogo-Arras, Gladys Schuler, Maik Suter, Willi Sweder, Kevin Tarlo, Kirk van Benthem, Jan van Goethem, Freddy Witt, Kristine L. TI Follow-Up Actions from Positive Results of In Vitro Genetic Toxicity Testing SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Review DE genotoxicity assays; in vitro positives; strategy; follow-up; ILSI HESI ID ERYTHROCYTE MICRONUCLEUS ASSAY; GENOTOXICITY TEST PROCEDURES; TANDEM REPEAT INSTABILITY; BACTERIAL MUTATION ASSAYS; THYMIDINE KINASE LOCUS; TERM TEST INFORMATION; MOUSE LYMPHOMA-CELLS; IWGT WORKING GROUP; VIVO COMET ASSAY; TOX PROGRAM AB Appropriate follow-up actions and decisions are needed when evaluating and interpreting clear positive results obtained in the in vitro assays used in the initial genotoxicity screening battery (i.e., the battery of tests generally required by regulatory authorities) to assist in overall risk-based decision making concerning the potential effects of human exposure to the agent under test. Over the past few years, the International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) Project Committee on the Relevance and Follow-up of Positive Results in In Vitro Genetic Toxicity (IVGT) Testing developed a decision process flow chart to be applied in case of clear positive results in vitro. It provides for a variety of different possibilities and allows flexibility in choosing follow-up action(s), depending on the results obtained in the initial battery of assays and available in-formation. The intent of the Review Subgroup was not to provide a prescriptive testing strategy, but rather to reinforce the concept of weighing the totality of the evidence. The Review Subgroup of the IVGT committee highlighted the importance of properly analyzing the existing data, and considering potential confounding factors (e. g., possible interactions with the test systems, presence of impurities, irrelevant metabolism), and chemical modes of action when analyzing and interpreting positive results in the in vitro genotoxicity assays and determining appropriate follow-up testing. The Review Subgroup also examined the characteristics, strengths, and limitations of each of the existing in vitro and in vivo genotoxicity assays to determine their usefulness in any follow-up testing. Environ. Mol. Mutagen. 52: 177-204, 2011. (C) 2010 Wiley-Liss, Inc. C1 [Dearfield, Kerry L.] USDA, Food Safety & Inspect Serv, Washington, DC 20250 USA. [Thybaud, Veronique] Vitry Alfortville Res Ctr, Vitry Sur Seine, France. [Cimino, Michael C.] US EPA, Off Pollut Prevent & Tox, Washington, DC 20460 USA. [Custer, Laura; Sweder, Kevin] Bristol Myers Squibb Co, Res & Dev, Dept Genet Toxicol, E Syracuse, NY USA. [Czich, Andreas] Deutschland GmbH, R&D Drug Safety Evaluat FFM, Sanofi Aventis, Hattersheim, Germany. [Hester, Susan] US EPA, Res Unit Cores IO, Res Triangle Pk, NC 27711 USA. [Kim, James H.] ILSI HESI, Washington, DC USA. [Kirkland, David] Covance Labs Ltd, Harrogate, England. [Levy, Dan D.] US FDA, Off Nutr Labeling & Dietary Supplements, College Pk, MD USA. [Lorge, Elisabeth] Servier Grp, Biol Servier, France. [Moore, Martha M.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Ouedraogo-Arras, Gladys] LOreal, Int Safety Res Dept, Aulnay Sous Bois, France. [Schuler, Maik] Pfizer Global Res & Dev, Drug Safety Res & Dev, Groton, CT USA. [Suter, Willi] Novartis Pharma AG, Preclin Safety GeneSafe, Basel, Switzerland. [Tarlo, Kirk] Amgen Inc, Thousand Oaks, CA 91320 USA. [van Benthem, Jan] Natl Inst Publ Hlth & Environm RIVM, Lab Hlth Protect Res, Bilthoven, Netherlands. [van Goethem, Freddy] Johnson & Johnson Pharmaceut R&D, Genet & Exploratory Toxicol, Beerse, Belgium. [Witt, Kristine L.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Kim, JH (reprint author), 1156 15th St NW,2nd Floor, Washington, DC 20005 USA. EM jkim@hesiglobal.org NR 138 TC 22 Z9 24 U1 7 U2 17 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD APR PY 2011 VL 52 IS 3 DI 10.1002/em.20617 PG 28 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 731GZ UT WOS:000288095600003 PM 20963811 ER PT J AU Short, DF Zemel, BS Gilsanz, V Kalkwarf, HJ Lappe, JM Mahboubi, S Oberfield, SE Shepherd, JA Winer, KK Hangartner, TN AF Short, D. F. Zemel, B. S. Gilsanz, V. Kalkwarf, H. J. Lappe, J. M. Mahboubi, S. Oberfield, S. E. Shepherd, J. A. Winer, K. K. Hangartner, T. N. TI Fitting of bone mineral density with consideration of anthropometric parameters SO OSTEOPOROSIS INTERNATIONAL LA English DT Article DE Bone; Bone growth; Bone mineral density; Model fitting; Orthogonal transformation; Smoothing ID X-RAY ABSORPTIOMETRY; PREDICTION MODEL; CHILDREN; ADOLESCENTS; DENSITOMETRY; MASS AB A new model describing normal values of bone mineral density in children has been evaluated, which includes not only the traditional parameters of age, gender, and race, but also weight, height, percent body fat, and sexual maturity. This model may constitute a better comparative norm for a specific child with given anthropometric values. Previous descriptions of children's bone mineral density (BMD) by age have focused on segmenting diverse populations by race and gender without adjusting for anthropometric variables or have included the effects of anthropometric variables over a relatively homogeneous population. Multivariate semi-metric smoothing (MS(2)) provides a way to describe a diverse population using a model that includes multiple effects and their interactions while producing a result that can be smoothed with respect to age in order to provide connected percentiles. We applied MS(2) to spine BMD data from the Bone Mineral Density in Childhood Study to evaluate which of gender, race, age, height, weight, percent body fat, and sexual maturity explain variations in the population's BMD values. By balancing high adjusted R (2) values and low mean square errors with clinical needs, a model using age, gender, race, weight, and percent body fat is proposed and examined. This model provides narrower distributions and slight shifts of BMD values compared to the traditional model, which includes only age, gender, and race. Thus, the proposed model might constitute a better comparative standard for a specific child with given anthropometric values and should be less dependent on the anthropometric characteristics of the cohort used to devise the model. The inclusion of multiple explanatory variables in the model, while creating smooth output curves, makes the MS(2) method attractive in modeling practically sized data sets. The clinical use of this model by the bone research community has yet to be fully established. C1 [Short, D. F.; Hangartner, T. N.] Wright State Univ, Dayton, OH 45435 USA. [Zemel, B. S.; Mahboubi, S.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Gilsanz, V.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Kalkwarf, H. J.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. [Lappe, J. M.] Creighton Univ, Omaha, NE 68178 USA. [Oberfield, S. E.] Columbia Univ, Med Ctr, New York, NY USA. [Shepherd, J. A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Winer, K. K.] NICHHD, Bethesda, MD 20892 USA. RP Hangartner, TN (reprint author), Wright State Univ, Dayton, OH 45435 USA. EM thomas.hangartner@wright.edu FU National Institute of Child Health and Human Development (NICHD) [N01-HD-1-3328] FX This work was funded by the National Institute of Child Health and Human Development (NICHD), contract number N01-HD-1-3328. NR 24 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD APR PY 2011 VL 22 IS 4 BP 1047 EP 1057 DI 10.1007/s00198-010-1284-4 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 728DN UT WOS:000287854500005 PM 20495903 ER PT J AU Samelson, EJ Christiansen, BA Demissie, S Broe, KE Zhou, Y Meng, CA Yu, W Cheng, X O'Donnell, CJ Hoffmann, U Genant, HK Kiel, DP Bouxsein, ML AF Samelson, E. J. Christiansen, B. A. Demissie, S. Broe, K. E. Zhou, Y. Meng, C. A. Yu, W. Cheng, X. O'Donnell, C. J. Hoffmann, U. Genant, H. K. Kiel, D. P. Bouxsein, M. L. TI Reliability of vertebral fracture assessment using multidetector CT lateral scout views: the Framingham Osteoporosis Study SO OSTEOPOROSIS INTERNATIONAL LA English DT Article DE Computed tomography; Lateral scout; Reliability; Scoutviews; Semiquantitative; Vertebral fracture ID X-RAY ABSORPTIOMETRY; COMPUTED-TOMOGRAPHY; PREVALENCE; WOMEN; HEART; IDENTIFICATION; RECOGNITION; RADIOGRAPHY; DIAGNOSIS; DEFORMITIES AB Two radiologists evaluated images of the spine from computed tomography (CT) scans on two occasions to diagnose vertebral fracture in 100 individuals. Agreement was fair to good for mild fractures, and agreement was good to excellent for more severe fractures. CT scout views are useful to assess vertebral fracture. We investigated inter-reader agreement between two radiologists and intra-reader agreement between duplicate readings for each radiologist, in assessment of vertebral fracture using a semi-quantitative method from lateral scout views obtained by CT. Participants included 50 women and 50 men (age 50-87 years, mean 70 years) in the Framingham Study. T4-L4 vertebrae were assessed independently by two radiologists on two occasions using a semi-quantitative scale as normal, mild, moderate, or severe fracture. Vertebra-specific prevalence of grade a parts per thousand yen1 (mild) fracture ranged from 3% to 5%. We found fair (kappa = 56-59%) inter-reader agreement for grade a parts per thousand yen1 vertebral fractures and good (kappa = 68-72%) inter-reader agreement for grade a parts per thousand yen2 fractures. Intra-reader agreement for grade a parts per thousand yen1 vertebral fracture was fair (kappa = 55%) for one reader and excellent for another reader (kappa = 77%), whereas intra-reader agreement for grade a parts per thousand yen2 vertebral fracture was excellent for both readers (kappa = 76% and 98%). Thoracic vertebrae were more difficult to evaluate than the lumbar region, and agreement was lowest (inter-reader kappa = 43%) for fracture at the upper (T4-T9) thoracic levels and highest (inter-reader kappa = 76-78%) for the lumbar spine (L1-L4). Based on a semi-quantitative method to classify vertebral fractures using CT scout views, agreement within and between readers was fair to good, with the greatest source of variation occurring for fractures of mild severity and for the upper thoracic region. Agreement was good to excellent for fractures of at least moderate severity. Lateral CT scout views can be useful in clinical research settings to assess vertebral fracture. C1 [Samelson, E. J.; O'Donnell, C. J.; Hoffmann, U.; Kiel, D. P.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Samelson, E. J.; Broe, K. E.; Meng, C. A.; Kiel, D. P.] Inst Aging Res Boston, Boston, MA USA. [Christiansen, B. A.; Bouxsein, M. L.] Beth Israel Deaconess Med Ctr, Ctr Adv Orthoped Studies, Boston, MA 02215 USA. [Christiansen, B. A.; Bouxsein, M. L.] Harvard Univ, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA. [Christiansen, B. A.] Univ Calif Davis, Dept Orthopaed, Sacramento, CA 95817 USA. [Demissie, S.; Zhou, Y.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Yu, W.] Beijing Union Med Coll Hosp, Beijing, Peoples R China. [Cheng, X.] Beijing Ji Shui Tan Hosp, Beijing, Peoples R China. [O'Donnell, C. J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Hoffmann, U.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Genant, H. K.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. [Genant, H. K.] Synarc Inc, San Francisco, CA USA. RP Samelson, EJ (reprint author), Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. EM Samelson@hrca.harvard.edu; bchristiansen@ucdavis.edu; demissie@bu.edu; broe@hrca.harvard.edu; zyanhua@bu.edu; Ching-AnMeng@hrca.harvard.edu; weiyu5508@yahoo.com; xiao65@263.net; codonnell@nih.gov; uhoffmann@partners.org; harry.genant@ucsf.edu; kiel@hrca.harvard.edu; mbouxsei@bidmc.harvard.edu RI Christiansen, Blaine/F-9021-2010; OI Kiel, Douglas/0000-0001-8474-0310 FU NIH [R01AR053986, R01AR/AG041398, K01 AR053118, T32 AG023480]; National Heart, Lung, and Blood Institute (NHLBI) (NIH/NHLBI) [N01-HC-25195] FX This work was supported by NIH R01AR053986, R01AR/AG041398, K01 AR053118, T32 AG023480, and by the National Heart, Lung, and Blood Institute (NHLBI) Framingham Heart Study (NIH/NHLBI Contract N01-HC-25195). NR 45 TC 17 Z9 20 U1 0 U2 1 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD APR PY 2011 VL 22 IS 4 BP 1123 EP 1131 DI 10.1007/s00198-010-1290-6 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 728DN UT WOS:000287854500012 PM 20495902 ER PT J AU Kelly, DL Myers, CS Abrams, MT Feldman, S Park, J McMahon, RP Shim, JC AF Kelly, D. L. Myers, C. S. Abrams, M. T. Feldman, S. Park, J. McMahon, R. P. Shim, J. -C. TI The impact of substance abuse on osteoporosis screening and risk of osteoporosis in women with psychotic disorders SO OSTEOPOROSIS INTERNATIONAL LA English DT Article DE Bone mineral density; Medicaid; Osteoporosis; Psychosis; Schizophrenia; Screening; Substance abuse ID BONE-MINERAL DENSITY; MEDICAL COMORBIDITY; UNITED-STATES; HIP FRACTURE; DRUG-ABUSE; SCHIZOPHRENIA; ALCOHOL; PREVALENCE; DEPRESSION; SERVICES AB Review of the 1-year prevalence of screening for osteoporosis and of osteoporosis or idiopathic fracture in Maryland Medicaid administrative records found that screening rates did not differ among women in the control population, women with psychosis, and women with major mood disorders, but were reduced compared to controls in women with substance use disorder, with or without psychosis. Prevalence of osteoporosis was increased compared to controls in women with major mood disorders or women over 55 dually diagnosed with psychosis and substance use disorder. Osteoporosis is a major public health concern. Substance abuse and psychosis may be risk factors, however, frequency of screening and disease risk in women with psychotic disorders and substance use disorder (SUD) remains unknown. This study examined rates (FY 2005) of osteoporosis screening and disease risk in Medicaid enrolled women aged 50 to 64 (N = 18,953). Four diagnostic groups were characterized: (1) psychosis, (2) SUD, (3) major mood disorder, and (4) controls. The interaction of psychosis and SUD on screening and disease prevalence of osteoporosis was tested. The prevalence of osteoporosis across the entire population was 6.7%. Four percent of those without an osteoporosis diagnosis received osteoporosis screening with no notable differences between psychosis and controls. Those with SUD, however, had a significant reduction in screening compared to controls (OR = 0.61, 95% CI = 0.40-0.91, p = 0.016). Women with a major mood disorder were more likely to have osteoporosis in their administrative record (OR = 1.32, 95% CI = 1.03-1.70, p = 0.028) compared to controls. Those who were dually diagnosed (SUD and psychosis) in the oldest ages (55-64 years) had a markedly higher prevalence of osteoporosis compared to controls (OR = 6.4 CI = 1.51-27.6, p = 0.012), whereas this interaction (SUD and psychosis) was not significant in the entire population over age 49. Osteoporosis screening in the Medicaid population is significantly lower for women with SUD, after adjusting for age, race, and Medicaid enrollment category. The prevalence of osteoporosis appears markedly elevated in those with major mood disorders and those over age 55 dually diagnosed with schizophrenia and SUD. C1 [Kelly, D. L.; Feldman, S.; McMahon, R. P.] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Baltimore, MD 21228 USA. [Myers, C. S.] NIDA, Intramural Res Program, Baltimore, MD USA. [Abrams, M. T.; Park, J.] Univ Maryland, Hilltop Inst, Baltimore, MD 21228 USA. [Shim, J. -C.] Inje Univ, Busan Paik Hosp, Dept Psychiat, Pusan, South Korea. [Shim, J. -C.] Inje Univ, Busan Paik Hosp, Clin Trial Ctr, Pusan, South Korea. RP Kelly, DL (reprint author), Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, POB 21247, Baltimore, MD 21228 USA. EM dkelly@mprc.umaryland.edu RI McMahon, Robert/C-5462-2009 FU NIH, National Institute on Drug Abuse; NIDA Residential Research Support Services [HHSN271200599091CADB] FX This study was supported by the Intramural Research Program, NIH, National Institute on Drug Abuse and the NIDA Residential Research Support Services Contract HHSN271200599091CADB. The authors wish to thank Cynthia Boddie-Willis, Susan Chen, and Nancy Svehla for their contributions to this work. NR 48 TC 3 Z9 4 U1 2 U2 4 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-941X EI 1433-2965 J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD APR PY 2011 VL 22 IS 4 BP 1133 EP 1143 DI 10.1007/s00198-010-1294-2 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 728DN UT WOS:000287854500013 PM 20533029 ER PT J AU Wright, JL Neuhouser, ML Lin, DW Kwon, EM Feng, ZD Ostrander, EA Stanford, JL AF Wright, Jonathan L. Neuhouser, Marian L. Lin, Daniel W. Kwon, Erika M. Feng, Ziding Ostrander, Elaine A. Stanford, Janet L. TI AMACR Polymorphisms, Dietary Intake of Red Meat and Dairy and Prostate Cancer Risk SO PROSTATE LA English DT Article DE prostate cancer; AMACR; red meat; dairy; SNP ID METHYLACYL-COA RACEMASE; CELLS IN-VITRO; SEQUENCE VARIANTS; PHYTANIC ACID; ALPHA; PRODUCTS; POPULATION; RECEPTOR; EXPRESSION; CONVERSION AB BACKGROUND. Alpha-methylacyl CoA racemase (AMACR) is an enzyme involved in fatty acids metabolism. One of AMACRs primary substrates, phytanic acid, is principally obtained from dietary red meat/dairy, which are associated with prostate cancer (PCa) risk. AMACR is also a tumor tissue biomarker over-expressed in PCa. In this study, we explored the potential relationship between AMACR polymorphisms, red meat/dairy intake, and PCa risk. METHODS. Caucasian participants from two population-based PCa case-control studies were included. AMACR single nucleotide polymorphisms (SNPs) were selected to capture variation across the gene and regulatory regions. Red meat and dairy intake was determined from food frequency questionnaires. The odds ratio (OR) of PCa (overall and by disease aggressiveness) was estimated by logistic and polytomous regression. Potential interactions between genotypes and dietary exposures were evaluated. RESULTS. Data from 1,309 cases and 1,267 controls were analyzed. Carriers of the variant T allele (rs2287939) had an OR of 0.81 (95% CI 0.68-0.97) for less aggressive PCa, but no alteration in risk for more aggressive PCa. Red meat consumption was positively associated with PCa risk, and the association was stronger for more aggressive disease (lowest vs. highest tertile OR = 1.55, 95% CI 1.10-2.20). No effect modification of AMACR polymorphisms by either dietary red meat or dairy intake on PCa risk was observed. CONCLUSIONS. PCa risk varied by level of red meat intake and by one AMACR SNP, but there was no evidence for gene-environment interaction. These findings suggest that the effects of AMACR polymorphisms and red meat and dairy on PCa risk are independent. Prostate 71: 498-506, 2011. (C) 2010 Wiley-Liss, Inc. C1 [Wright, Jonathan L.] Univ Washington, Med Ctr, Dept Urol, Sch Med, Seattle, WA 98195 USA. [Wright, Jonathan L.; Neuhouser, Marian L.; Lin, Daniel W.; Feng, Ziding; Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Kwon, Erika M.; Ostrander, Elaine A.] NHGRI, Canc Genet Branch, Bethesda, MD 20892 USA. [Stanford, Janet L.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. RP Wright, JL (reprint author), Univ Washington, Med Ctr, Dept Urol, Sch Med, Hlth Sci Bldg,1959 NE Pacific,BB 1115,Box 356510, Seattle, WA 98195 USA. EM jlwright@u.washington.edu OI Ostrander, Elaine/0000-0001-6075-9738 FU NIH [R01 CA056678, R01 CA092579, T32 CA009168-30, P50 CA097186]; Fred Hutchinson Cancer Research Center; National Human Genome Research Institute FX Grant sponsor: NIH; Grant numbers: R01 CA056678, R01 CA092579, T32 CA009168-30, P50 CA097186; Grant sponsor: The Fred Hutchinson Cancer Research Center; Grant sponsor: The Intramural Program of the National Human Genome Research Institute. NR 29 TC 14 Z9 15 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-4137 J9 PROSTATE JI Prostate PD APR PY 2011 VL 71 IS 5 BP 498 EP 506 DI 10.1002/pros.21267 PG 9 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 731UU UT WOS:000288135700007 PM 20945498 ER PT J AU Kosti, O Xu, X Veenstra, TD Hsing, AW Chu, LW Goldman, L Bebu, I Collins, S Dritschilo, A Lynch, JH Goldman, R AF Kosti, Ourania Xu, Xia Veenstra, Timothy D. Hsing, Ann W. Chu, Lisa W. Goldman, Lenka Bebu, Ionut Collins, Sean Dritschilo, Anatoly Lynch, John H. Goldman, Radoslav TI Urinary Estrogen Metabolites and Prostate Cancer Risk: A Pilot Study SO PROSTATE LA English DT Article DE prostate cancer; estrogen metabolites; benign prostatic hyperplasia; case-control study ID MASS SPECTROMETRY METHOD; ENDOGENOUS SEX-HORMONES; RECEPTOR-BETA; UNITED-STATES; SERUM HORMONES; BREAST-CANCER; NOBLE RATS; 2-METHOXYESTRADIOL; DISEASE; 4-HYDROXYESTRADIOL AB BACKGROUND. The high incidence of and few identified risk factors for prostate cancer underscore the need to further evaluate markers of prostate carcinogenesis. The aim of this pilot study was to evaluate urinary estrogen metabolites as a biomarker of prostate cancer risk. METHODS. Using a liquid chromatography-tandem mass spectrometry method, urinary concentrations of 15 estrogen metabolites were determined in 77 prostate cancer cases, 77 healthy controls, and 37 subjects who had no evidence of prostate cancer after a prostate biopsy. RESULTS. We observed an inverse association between the urinary 16-ketoestradiol (16-KE2) and 17-epiestriol (17-epiE3)-metabolites with high estrogenic activity-and prostate cancer risk. Men in the lowest quartile of 16-KE2, had a 4.6-fold risk of prostate cancer (OR = 4.62, 95% CI = 1.34-15.99), compared with those in the highest quartile. CONCLUSIONS. We observed modest differences in estrogen metabolite concentrations between prostate cancer patients and subjects without cancer. Larger studies with both androgen and estrogen measurements are needed to confirm these results to clarify further whether estrogen metabolites are independent biomarkers for prostate cancer risk and whether androgen/estrogen imbalance influences prostate cancer risk. Prostate 71: 507-516, 2011. (C) 2010 Wiley-Liss, Inc. C1 [Goldman, Radoslav] Georgetown Univ, Dept Oncol, LCC, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. [Xu, Xia; Veenstra, Timothy D.] NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. [Hsing, Ann W.; Chu, Lisa W.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. [Bebu, Ionut] Georgetown Univ, Dept Biostat Bioinformat & Biomath, Washington, DC 20057 USA. [Collins, Sean; Dritschilo, Anatoly] Georgetown Univ Hosp, Washington, DC 20007 USA. [Lynch, John H.] Georgetown Univ, Dept Urol, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. RP Goldman, R (reprint author), Georgetown Univ, Dept Oncol, LCC, Lombardi Comprehens Canc Ctr, 3800 Reservoir Rd NW,S183, Washington, DC 20057 USA. EM rg26@georgetown.edu FU National Institutes of Health National Center for Research Resources [M01RR-023942]; Department of Defense [PC081609] FX We wish to thank Allison Pollock and Anthony Roy Orden for the recruitment of study participants and Dr. Borges, Department of Urology, Veterans Administration Medical Center, for facilitating recruitment at the VA hospital. The Clinical Molecular Epidemiology Shared Resources at the Lombardi Comprehensive Cancer Center provided services for questionnaire data entry. This project was conducted through the General Clinical Research Center at Georgetown University and supported by the National Institutes of Health National Center for Research Resources, grant M01RR-023942. This study was supported in part by the Department of Defense Prostate Cancer Research Program grant PC081609 awarded to RG. NR 45 TC 5 Z9 5 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-4137 J9 PROSTATE JI Prostate PD APR PY 2011 VL 71 IS 5 BP 507 EP 516 DI 10.1002/pros.21262 PG 10 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 731UU UT WOS:000288135700008 PM 20886539 ER PT J AU Leon, CA Schumacher, J Kluck, N Herold, C Schulze, TG Propping, P Rietschel, M Cichon, S Nothen, MM Abou Jamra, R AF Leon, Chady Abboud Schumacher, Johannes Kluck, Nadine Herold, Christine Schulze, Thomas G. Propping, Peter Rietschel, Marcella Cichon, Sven Noethen, Markus M. Abou Jamra, Rami TI Association study of the GRIA1 and CLINT1 (Epsin 4) genes in a German schizophrenia sample SO PSYCHIATRIC GENETICS LA English DT Letter C1 [Leon, Chady Abboud; Schumacher, Johannes; Kluck, Nadine; Propping, Peter; Cichon, Sven; Noethen, Markus M.; Abou Jamra, Rami] Univ Bonn, Inst Human Genet, D-53127 Bonn, Germany. [Herold, Christine] Univ Bonn, Inst Med Biometry Informat & Epidemiol, D-53127 Bonn, Germany. [Schulze, Thomas G.; Rietschel, Marcella] Cent Inst Mental Hlth, Div Genet Epidemiol Psychiat, D-6800 Mannheim, Germany. [Abou Jamra, Rami] Univ Erlangen Nurnberg, Inst Human Genet, Erlangen, Germany. [Schulze, Thomas G.] NIMH, Unit Genet Basis Mood & Anxiety Disorders, NIH, Bethesda, MD 20892 USA. RP Abou Jamra, R (reprint author), Univ Bonn, Inst Human Genet, Sigmund Freud St 25, D-53127 Bonn, Germany. EM rami.aboujamra@uni-bonn.de RI Schulze, Thomas/H-2157-2013; Cichon, Sven/H-8803-2013; Cichon, Sven/B-9618-2014; Abou Jamra, Rami/I-4805-2015; Schumacher, Johannes/F-4970-2015; OI Cichon, Sven/0000-0002-9475-086X; Cichon, Sven/0000-0002-9475-086X; Abou Jamra, Rami/0000-0002-1542-1399; Schumacher, Johannes/0000-0001-9217-6457; Nothen, Markus/0000-0002-8770-2464 NR 4 TC 4 Z9 4 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8829 J9 PSYCHIAT GENET JI Psychiatr. Genet. PD APR PY 2011 VL 21 IS 2 BP 114 EP 114 DI 10.1097/YPG.0b013e328341a334 PG 1 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 727ZK UT WOS:000287841700009 PM 21116212 ER PT J AU Flynn, PM Cunningham, CK Rudy, B Wilson, CM Kapogiannis, B Worrell, C Bethel, J Monte, D Bojan, K AF Flynn, Patricia M. Cunningham, Coleen K. Rudy, Bret Wilson, Craig M. Kapogiannis, Bill Worrell, Carol Bethel, James Monte, Dina Bojan, Kelly CA Adolescent Med Trials Network HIV TI Hepatitis B Vaccination in HIV-Infected Youth: A Randomized Trial of Three Regimens SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; hepatitis B vaccination; adolescents; Engerix B; Twinrix ID HUMAN-IMMUNODEFICIENCY-VIRUS; IMPAIRED RESPONSE; HOMOSEXUAL MEN; SEROLOGIC RESPONSE; ANTIBODY-RESPONSE; ADULT PATIENTS; A VACCINE; CHILDREN; IMMUNIZATION; ADOLESCENTS AB Background: HIV-infected youth are at risk of hepatitis B infection and should be vaccinated. Previous reports suggest reduced response to standard hepatitis B vaccine regimens. Methods: HIV-infected youth, aged 12 to younger than 25 years, were randomly assigned to one of three treatment arms: Arm 1: Engerix B, 20 mg HBsAg; Arm 2: Engerix B (GlaxoSmithKline, Rixensart, Belgium), 40 mg; and Arm 3: Twinrix (GlaxoSmithKline, Rixensart, Belgium), 20 mg HBsAg combined with 720 ELU hepatitis A antigen. Vaccines were administered at Weeks 0, 4, and 24. Results: Characteristics of evaluable patients (n = 336) at entry were similar in the study arms. At enrollment, median CD4(+) T-cell count was 460 cells/mm(3) (interquartile range, 305-668); 13% were less than 200 cells/mm(3). Among Engerix B, 20-mg recipients, 60.4% responded to vaccine (HBsAb 10 IU/mL or greater at Week 28). Improved vaccine response was seen in recipients of Engerix B, 40 mg (73.2% versus Arm 1, P = 0.04) and Twinrix (75.4% versus Arm 1, P = 0.02). In multivariate analysis, only baseline CD4(+) T-cell count and study arm were independent predictors of vaccine response. Conclusions: In HIV-infected youth, a three-dose vaccination regimen with Engerix B, 40 mg, or Twinrix and higher baseline CD4(+) T-cell counts were independently associated with improved vaccine response. C1 [Flynn, Patricia M.] St Jude Childrens Res Hosp, Dept Infect Dis, Memphis, TN 38105 USA. [Flynn, Patricia M.] Univ Tennessee, Hlth Sci Ctr, Dept Pediat, Memphis, TN USA. [Flynn, Patricia M.] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN USA. [Cunningham, Coleen K.] Duke Univ, Dept Pediat, Sch Med, Durham, NC 27706 USA. [Rudy, Bret] NYU, Dept Pediat, Sch Med, New York, NY 10016 USA. [Wilson, Craig M.] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA. [Kapogiannis, Bill; Worrell, Carol] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, NIH, Rockville, MD USA. [Bethel, James; Monte, Dina] Westat Corp, Rockville, MD USA. [Bojan, Kelly] Core Ctr, Adolescent Div, Chicago, IL USA. RP Flynn, PM (reprint author), St Jude Childrens Res Hosp, Dept Infect Dis, 262 Danny Thomas Pl, Memphis, TN 38105 USA. EM pat.flynn@stjude.org RI Mussi-Pinhata, Marisa/G-6568-2012; Inca, Inct/K-2204-2013 FU Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) from the National Institutes of Health through the Eunice Kennedy Shriver National Institute of Child Health and Human Development [U01 HD 040533, U01 HD 040474]; National Institutes on Drug Abuse and Mental Health; National Center for Research Resources, National Institutes of Health; Department of Health and Human Services; Children's National Medical Center; GCRC [M01RR020359, M01RR05096, M01RR00083-42, M01RR01271]; Tulane University/Louisiana State University; University of California at San Francisco; National Institute of Allergy and Infectious Diseases (NIAID) [U01 AI068632]; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institute of Mental Health (NIMH) [AI068632]; NICHD [N01-DK-9-001/HHSN267200800001C] FX 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 Eunice Kennedy Shriver National Institute of Child Health and Human Development (B. Kapogiannis, R. Hazra, S. Lee, C. Worrell) with supplemental funding from the National Institutes on Drug Abuse (N. Borek) and Mental Health (P. Brouwers, S. Allison). Additional support for this study was provided by grants from the General Clinical Research Center (GCRC) Program of the National Center for Research Resources, National Institutes of Health, and Department of Health and Human Services. The following grants provided support: Children's National Medical Center, GCRC Grant M01RR020359; Tulane University/Louisiana State University, GCRC Grant M01RR05096; and University of California at San Francisco, GCRC Grant M01RR00083-42 and Pediatric Clinical Research Grant M01RR01271. The protocol was coendorsed by the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT). Overall support for the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) was provided by the National Institute of Allergy and Infectious Diseases (NIAID) (U01 AI068632), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Institute of Mental Health (NIMH) (AI068632). Support of the sites was provided by the National Institute of Allergy and Infectious Diseases (NIAID); the NICHD International and Domestic Pediatric and Maternal HIV Clinical Trials Network was funded by NICHD (contract number N01-DK-9-001/HHSN267200800001C). NR 39 TC 19 Z9 19 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD APR PY 2011 VL 56 IS 4 BP 325 EP 332 DI 10.1097/QAI.0b013e318203e9f2 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 726QH UT WOS:000287740700014 PM 21350366 ER PT J AU Read, SW Ciccone, EJ Mannon, PJ Yao, MD Chairez, CL Davey, RT Kovacs, JA Sereti, I AF Read, Sarah W. Ciccone, Emily J. Mannon, Peter J. Yao, Michael D. Chairez, Cheryl L. Davey, Richard T. Kovacs, Joseph A. Sereti, Irini TI The Effect of Intermittent IL-2 Therapy on CD4 T Cells in the Gut in HIV-1-Infected Patients SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE CD4; gastrointestinal tract; HIV; IL-2; mucosa ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-INFECTED PATIENTS; ACTIVE ANTIRETROVIRAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; GASTROINTESTINAL-TRACT; SUBCUTANEOUS INTERLEUKIN-2; TYPE-1 INFECTION; DEPLETION; LYMPHOCYTES; TISSUE AB We sought to determine the effects of interleukin-2 administered in combination with antiretroviral therapy (ART) on CD4(+) T cells in the gut. Lymphocytes from whole blood, colon, and terminal ileum of HIV-infected adults treated with interleukin-2 and ART or ART alone were examined. There were no differences between groups in the proportion of CD4(+) T cells or in expression of CD25 or Ki67 by CD4(+) T cells in the gut. Although IL-2 administration leads to expansion of peripheral blood CD4(+) T cells, there is no alteration in the proportion or activation of CD4(+) T cells in the gut mucosa. C1 [Read, Sarah W.] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. [Ciccone, Emily J.; Chairez, Cheryl L.; Davey, Richard T.; Sereti, Irini] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Mannon, Peter J.] Univ Alabama, Div Gastroenterol & Hepatol, Birmingham, AL USA. [Yao, Michael D.] NIAID, Lab Host Defenses, Bethesda, MD 20892 USA. [Kovacs, Joseph A.] NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Read, SW (reprint author), 6700B Rockledge Dr,Room 5100, Bethesda, MD 20892 USA. EM readsa@niaid.nih.gov FU NIH, NIAID; Critical Care Medicine Department; National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX Supported in part by the Intramural Program of the NIH, NIAID, and Critical Care Medicine Department. Additionally, 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. NR 20 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD APR PY 2011 VL 56 IS 4 BP 340 EP 343 DI 10.1097/QAI.0b013e31820bf84c PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 726QH UT WOS:000287740700016 PM 21350367 ER PT J AU Wang, QH Dinse, GE AF Wang, Qihua Dinse, Gregg E. TI Linear regression analysis of survival data with missing censoring indicators SO LIFETIME DATA ANALYSIS LA English DT Article DE Asymptotic normality; Censoring indicator; Imputation; Inverse probability weighting; Least squares; Missing at random; Regression calibration ID MULTIPLE IMPUTATION METHODS; PRODUCT-LIMIT ESTIMATORS; COMPETING RISKS MODEL; PROPENSITY SCORE; EFFICIENT ESTIMATION; FAILURE; COEFFICIENTS; INFORMATION; EXISTENCE; TIME AB Linear regression analysis has been studied extensively in a random censorship setting, but typically all of the censoring indicators are assumed to be observed. In this paper, we develop synthetic data methods for estimating regression parameters in a linear model when some censoring indicators are missing. We define estimators based on regression calibration, imputation, and inverse probability weighting techniques, and we prove all three estimators are asymptotically normal. The finite-sample performance of each estimator is evaluated via simulation. We illustrate our methods by assessing the effects of sex and age on the time to non-ambulatory progression for patients in a brain cancer clinical trial. C1 [Dinse, Gregg E.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. [Wang, Qihua] Yunnan Univ, Dept Math & Stat, Kunming 650091, Peoples R China. [Wang, Qihua] Chinese Acad Sci, Acad Math & Syst Sci, Beijing 100190, Peoples R China. RP Dinse, GE (reprint author), NIEHS, Biostat Branch, POB 12233, Res Triangle Pk, NC 27709 USA. EM dinse@niehs.nih.gov FU National Science Fund for Distinguished Young Scholars in China [10725106]; National Natural Science Foundation of China [10671198]; National Science Fund for Creative Research Groups in China; research Grants Council of Hong Kong [HKU 7050/06P]; Key Lab of Random Complex Structures and Data Science, CAS; NIH, National Institute of Environmental Health Sciences [Z01-ES-045007-13] FX Qihua Wang's research was supported by the National Science Fund for Distinguished Young Scholars in China (10725106), the National Natural Science Foundation of China (10671198), the National Science Fund for Creative Research Groups in China, the research Grants Council of Hong Kong (HKU 7050/06P), and the grant from Key Lab of Random Complex Structures and Data Science, CAS. Gregg Dinse's research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES-045007-13). The authors thank Dr. Shyamal Peddada and Dr. David Dunson, as well as the editors and referees, for their many helpful comments. NR 36 TC 5 Z9 7 U1 3 U2 14 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1380-7870 J9 LIFETIME DATA ANAL JI Lifetime Data Anal. PD APR PY 2011 VL 17 IS 2 BP 256 EP 279 DI 10.1007/s10985-010-9175-8 PG 24 WC Mathematics, Interdisciplinary Applications; Statistics & Probability SC Mathematics GA 725RT UT WOS:000287664500005 PM 20559722 ER PT J AU Qin, M Entezam, A Usdin, K Huang, TJ Liu, ZH Hoffman, GE Smith, CB AF Qin, Mei Entezam, Ali Usdin, Karen Huang, Tianjian Liu, Zhong-Hua Hoffman, Gloria E. Smith, Carolyn B. TI A mouse model of the fragile X premutation: Effects on behavior, dendrite morphology, and regional rates of cerebral protein synthesis SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Fragile x syndrome; Fragile x premutation; FMRP; Fmr1; Hyperactivity; Anxiety; Dendritic spine morphology; Protein synthesis; Social interaction ID MENTAL-RETARDATION PROTEIN; FMR1 MESSENGER-RNA; CGG-REPEAT; TREMOR/ATAXIA-SYNDROME; STATUS CATEGORIES; FULL MUTATION; KNOCKOUT MICE; IN-VIVO; MALES; TRANSLATION AB Carriers of FMR1 premutation alleles have 55-200 CGG repeats in the 5' untranslated region of the gene. These individuals are at risk for fragile X associated primary ovarian insufficiency (females) and, in late life, fragile X associated tremor and ataxia syndrome (males, and to a lesser extent, females). Premutation carrier status can also be associated with autism spectrum disorder, attention deficit hyperactivity disorder, and some cognitive deficits. In premutation carriers, FMR1 mRNA levels are often higher than those with normal sized alleles. In contrast, in subjects with full mutation alleles, (>200 repeats) the FMR1 gene is silenced and FMR1 mRNA and its product, FMRP, are absent. We have studied a male knock-in (KI) mouse model of the fragile X premutation (120-140 repeats) during young adulthood. In comparison to wild type, KI mice were hyperactive, exhibited less anxiety in both the open field and the elevated zero maze, were impaired on the passive avoidance test, and showed some subtle deficits on a test of social interaction. Motor learning as assessed by the rotarod test was normal. Dendritic arbors were less complex and spine densities and lengths increased in medial prefrontal cortex, basal lateral amygdala, and hippocampus compared with wild type. Regional rates of cerebral protein synthesis measured in vivo in KI mice were increased. KI mice also had elevated levels of Fmr1 mRNA and decreased levels of FMRP. Our results highlight similarities in phenotype between KI and Fmr1 knockout mice and suggest that the decreased concentration of FMRP contributes to the phenotype in young adult KI mice. Published by Elsevier Inc. C1 [Qin, Mei; Huang, Tianjian; Liu, Zhong-Hua; Smith, Carolyn B.] NIMH, Sect Neuroadaptat & Prot Metab, NIH, Bethesda, MD 20892 USA. [Entezam, Ali; Usdin, Karen] NIDDKD, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. [Hoffman, Gloria E.] Morgan State Univ, Dept Biol, Baltimore, MD 21251 USA. RP Smith, CB (reprint author), NIMH, Sect Neuroadaptat & Prot Metab, NIH, Bldg 10,Rm 2D56,10 Ctr Dr,MSC 1298, Bethesda, MD 20892 USA. EM beebe@mail.nih.gov FU National Institute of Mental Health; National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health FX We thank Zengyan Xia for overseeing the breeding colony and Tom Burlin for analyzing plasma samples for amino acid concentrations. The research was supported by the Intramural Research Programs of the National Institute of Mental Health and the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. NR 58 TC 48 Z9 49 U1 1 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD APR PY 2011 VL 42 IS 1 BP 85 EP 98 DI 10.1016/j.nbd.2011.01.008 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 726MS UT WOS:000287727000008 PM 21220020 ER PT J AU Depboylu, C Weihe, E Eiden, LE AF Depboylu, Candan Weihe, Eberhard Eiden, Lee E. TI COX1 and COX2 expression in non-neuronal cellular compartments of the rhesus macaque brain during lentiviral infection SO NEUROBIOLOGY OF DISEASE LA English DT Article DE AIDS; Antiretroviral treatment; Encephalitis; Microglia; Prostaglandins ID SIMIAN IMMUNODEFICIENCY VIRUS; PROSTAGLANDIN ENDOPEROXIDE SYNTHASE; CENTRAL-NERVOUS-SYSTEM; NITRIC-OXIDE SYNTHASE; INDOLEAMINE 2,3-DIOXYGENASE; INDUCIBLE CYCLOOXYGENASE; MOLECULAR-BIOLOGY; MICROGLIAL CELLS; INTERFERON-GAMMA; UP-REGULATION AB Recent evidence suggests that cyclooxygenases COX1 and COX2 differentially affect brain immunity. Limited data exist about their expressional changes in neurodegenerative diseases such as neuro-AIDS. Here, we analyzed the regulation of non-neuronal COX1/2 expression in rhesus macaque brain during infection with SIV(delta 670) and antiretroviral treatment. COX1 was constitutively expressed in microglia and endothelial cells and was not changed in early SIV infection. Late stage of disease was characterized by increased COX1 expression in globally activated microglia, macrophage nodules, infiltrates, and multinucleated giant cells. Endothelial COX1 expression was unaltered. In contrast, COX2 was not expressed in non-neuronal cells in the brain of uninfected and asymptomatically Sly-infected monkeys but was induced in nodule- and syncytium-forming macrophages and in endothelial cells in areas with infiltrates and SW in monkeys with AIDS. Antiretroviral treatment of AIDS-diseased monkeys with 6-chloro-2',3'-dideoxyguanosine markedly reduced Sly burden, appearance of COX1 positive macrophage nodules, giant cells, and infiltrates, and COX2 induction in the brain. However, the number of COX1-positive diffuse microglia was still increased in antiretrovirally treated animals as compared to uninfected or asymptomatic Sly-infected monkeys. Our data imply that both COX isoforms are differentially regulated and may distinctly modulate local immune responses in the brain during lentiviral disease. Published by Elsevier Inc. C1 [Eiden, Lee E.] NIMH, SMN, LCMR, IRP, Bethesda, MD 20892 USA. [Depboylu, Candan; Weihe, Eberhard] Univ Marburg, Dept Anat & Cell Biol, D-3550 Marburg, Germany. [Depboylu, Candan] Univ Marburg, Dept Neurol, Marburg, Germany. RP Eiden, LE (reprint author), NIMH, SMN, LCMR, IRP, Bldg 49,Room 5A-38,9000 Rockville Pike, Bethesda, MD 20892 USA. EM eidenl@mail.nih.gov OI Eiden, Lee/0000-0001-7524-944X FU Volkswagen Stiftung; NIMH-IRP FX The financial support of the Volkswagen Stiftung is gratefully acknowledged. This project was supported in part by the NIMH-IRP. We thank Hiroaki Mitsuya of the Experimental Retrovirology Section, HIV and AIDS Malignancy Branch, Center for Clinical Research, NCI, NIH, for his collaboration in the initial stages of this project and continued interest in it. We are especially grateful to Dianne Rausch, Division of Mental Disorders, Behavioral Research and AIDS, NIMH, for advice and encouragement in the conduct of the work and the preparation of this manuscript. The National Institutes of Health AIDS Research and Reference Program kindly provided us with antibodies against SIV. NR 56 TC 6 Z9 7 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 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD APR PY 2011 VL 42 IS 1 BP 108 EP 115 DI 10.1016/j.nbd.2011.01.011 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 726MS UT WOS:000287727000010 PM 21220019 ER PT J AU Gillette, WK Esposito, D Taylor, TE Hopkins, RF Bagni, RK Hartley, JL AF Gillette, William K. Esposito, Dominic Taylor, Troy E. Hopkins, Ralph F. Bagni, Rachel K. Hartley, James L. TI Purify First: Rapid expression and purification of proteins from XMRV SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article DE XMRV; Protein purification; Small scale purification; Parallel purification ID STRUCTURAL GENOMICS; VIRUS; SITE AB Purifying proteins from recombinant sources is often difficult, time-consuming, and costly. We have recently instituted a series of improvements in our protein purification pipeline that allows much more accurate choice of expression host and conditions and purification protocols. The key elements are parallel cloning, small scale parallel expression and lysate preparation, and small scale parallel protein purification. Compared to analyzing expression data only, results from multiple small scale protein purifications predict success at scale-up with greatly improved reliability. Using these new procedures we purified eight of nine proteins from xenotropic murine leukemia virus-related virus (XMRV) on the first attempt at large scale. (C) 2010 Elsevier Inc. All rights reserved. C1 [Gillette, William K.; Esposito, Dominic; Taylor, Troy E.; Hopkins, Ralph F.; Bagni, Rachel K.; Hartley, James L.] NCI Frederick, Prot Express Lab, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Hartley, JL (reprint author), NCI Frederick, Prot Express Lab, SAIC Frederick Inc, POB B,1050 Boyles St,301-846-7375,Bldg 327,Room 4, Frederick, MD 21702 USA. EM hartley@ncifcrf.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Research FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E, and by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. NR 13 TC 5 Z9 5 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD APR PY 2011 VL 76 IS 2 BP 238 EP 247 DI 10.1016/j.pep.2010.12.003 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 716ID UT WOS:000286961400012 PM 21146612 ER PT J AU Spiga, O Summa, D Cirri, S Bernini, A Venditti, V De Chiara, M Priora, R Frosali, S Margaritis, A Di Giuseppe, D Di Simplicio, P Niccolai, N AF Spiga, Ottavia Summa, Domenico Cirri, Simone Bernini, Andrea Venditti, Vincenzo De Chiara, Matteo Priora, Raffaella Frosali, Simona Margaritis, Antonios Di Giuseppe, Danila Di Simplicio, Paolo Niccolai, Neri TI A Structurally Driven Analysis of Thiol Reactivity in Mammalian Albumins SO BIOPOLYMERS LA English DT Article DE thiolation rate; protein structure and function; atom depth analysis; MD simulations; homology modeling ID BOVINE SERUM-ALBUMIN; EXCHANGE; PLASMA; MODEL; HOMOCYSTEINE; PREDICTION; PEROXIDES; BINDING AB Understanding the structural basis of protein redox activity is still an open question. Hence, by using a structural genomics approach, different albumins have been chosen to correlate protein structural features with the corresponding reaction rates of thiol exchange between albumin and disulfide DTNB. Predicted structures of rat, porcine, and bovine albumins have been compared with the experimentally derived human albumin. High structural similarity among these four albumins can be observed, in spite of their markedly different reactivity with DTNB. Sequence alignments offered preliminary hints on the contributions of sequence-specific local environments modulating albumin reactivity. Molecular dynamics simulations performed on experimental and predicted albumin structures reveal that thiolation rates are influenced by hydrogen bonding pattern and stability of the acceptor C34 sulphur atom with donor groups of nearby residues. Atom depth evolution of albumin C34 thiol groups has been monitored during Molecular Dynamic trajectories. The most reactive albumins appeared also the ones presenting the C34 sulphur atom on the protein surface with the highest accessibility. High C34 sulphur atom reactivity in rat and porcine albumins seems to be determined by the presence of additional positively charged amino acid residues favoring both the C34 S(-) form and the approach of DTNB. (C) 2010 Wiley Periodicals, Inc. Biopolymers 95: 278-285, 2011. C1 [Spiga, Ottavia; Cirri, Simone; Bernini, Andrea; De Chiara, Matteo; Niccolai, Neri] Univ Siena, Dept Mol Biol, I-53100 Siena, Italy. [Spiga, Ottavia; Cirri, Simone; Bernini, Andrea; De Chiara, Matteo; Niccolai, Neri] SienaBiografix Srl, I-53100 Siena, Italy. [Summa, Domenico; Priora, Raffaella; Frosali, Simona; Margaritis, Antonios; Di Giuseppe, Danila; Di Simplicio, Paolo] Univ Siena, Pharmacol Unit, Dept Neurosci, I-53100 Siena, Italy. [Venditti, Vincenzo] NIDDK, Chem Phys Lab, Bethesda, MD 20892 USA. RP Niccolai, N (reprint author), Univ Siena, Dept Mol Biol, Via Laterina 8, I-53100 Siena, Italy. EM niccolai@unisi.it RI Venditti, Vincenzo/A-9411-2013; Bernini, Andrea/H-9412-2012; OI Bernini, Andrea/0000-0002-7528-2749; De Chiara, Matteo/0000-0003-1014-350X FU University of Siena FX Contract grant sponsor: University of Siena NR 38 TC 8 Z9 9 U1 0 U2 9 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PD APR PY 2011 VL 95 IS 4 BP 278 EP 285 DI 10.1002/bip.21577 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 719NT UT WOS:000287212200007 PM 21280023 ER PT J AU Strasak, AM Umlauf, N Pfeiffer, RM Lang, S AF Strasak, Alexander M. Umlauf, Nikolaus Pfeiffer, Ruth M. Lang, Stefan TI Comparing penalized splines and fractional polynomials for flexible modelling of the effects of continuous predictor variables SO COMPUTATIONAL STATISTICS & DATA ANALYSIS LA English DT Article DE Generalized additive models; Simulation study; Smoothing ID STRUCTURED ADDITIVE REGRESSION; BAYESIAN P-SPLINES; SMOOTHING PARAMETER-ESTIMATION; PENALTIES; SELECTION AB P(enalized)-splines and fractional polynomials (FPs) have emerged as powerful smoothing techniques with increasing popularity in applied research. Both approaches provide considerable flexibility, but only limited comparative evaluations of the performance and properties of the two methods have been conducted to date. Extensive simulations are performed to compare FPs of degree 2 (FP2) and degree 4 (FP4) and two variants of P-splines that used generalized cross validation (GCV) and restricted maximum likelihood (REML) for smoothing parameter selection. The ability of P-splines and FPs to recover the "true" functional form of the association between continuous, binary and survival outcomes and exposure for linear, quadratic and more complex, non-linear functions, using different sample sizes and signal to noise ratios is evaluated. For more curved functions FP2, the current default setting in implementations for fitting FPs in R, STATA and SAS, showed considerable bias and consistently higher mean squared error (MSE) compared to spline-based estimators and FP4, that performed equally well in most simulation settings. FPs however, are prone to artefacts due to the specific choice of the origin, while P-splines based on GCV reveal sometimes wiggly estimates in particular for small sample sizes. Application to a real dataset illustrates the different features of the two approaches. (C) 2010 Elsevier B.V. All rights reserved. C1 [Umlauf, Nikolaus; Lang, Stefan] Univ Innsbruck, A-6020 Innsbruck, Austria. [Strasak, Alexander M.] Innsbruck Med Univ, A-6020 Innsbruck, Austria. [Pfeiffer, Ruth M.] NCI, Bethesda, MD 20892 USA. RP Lang, S (reprint author), Univ Innsbruck, Univ Str 15, A-6020 Innsbruck, Austria. EM stefan.lang@uibk.ac.at RI Lang, Stefan/E-7500-2010; Pfeiffer, Ruth /F-4748-2011 OI Lang, Stefan/0000-0003-0739-3858; NR 38 TC 4 Z9 4 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-9473 J9 COMPUT STAT DATA AN JI Comput. Stat. Data Anal. PD APR 1 PY 2011 VL 55 IS 4 BP 1540 EP 1551 DI 10.1016/j.csda.2010.10.019 PG 12 WC Computer Science, Interdisciplinary Applications; Statistics & Probability SC Computer Science; Mathematics GA 713DU UT WOS:000286716000004 ER PT J AU Murphy, G Devesa, SS Cross, AJ Inskip, PD McGlynn, KA Cook, MB AF Murphy, Gwen Devesa, Susan S. Cross, Amanda J. Inskip, Peter D. McGlynn, Katherine A. Cook, Michael B. TI Sex disparities in colorectal cancer incidence by anatomic subsite, race and age SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE colorectal cancer; sex ratio; incidence; SEER program; epidemiology; neoplasms ID LARGE-BOWEL-CANCER; UNITED-STATES; MICROSATELLITE INSTABILITY; DIABETES-MELLITUS; AMERICAN-INDIANS; MEAT CONSUMPTION; ALASKA-NATIVES; RISK; WOMEN; COLON AB Although incidence of colorectal cancer (CRC) in the United States has declined in recent years, rates remain higher in men than in women and the male-to-female incidence rate ratio (MF IRR) increases progressively across the colon from the cecum to the rectum. Rates among races/ethnicities other than Whites or Blacks have not been frequently reported. To examine CRC rates by sex across anatomic subsite, age and racial/ethnic groups, we used the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) program for cases diagnosed among residents of 13 registries during 1992-2006. Incidence rates were expressed per 100,000 person-years and age-adjusted to the 2000 US Standard Population; MF IRR and 95% confidence intervals were also calculated. Among each racial/ethnic group, the MF IRR increased fairly monotonically from close to unity for cecal cancers to 1.81 (Hispanics) for rectal cancers. MF IRRs increased with age most rapidly for distal colon cancers from <1.0 at ages <50 years to 1.4-1.9 at older ages. The MF IRR for rectal cancers also rose with age from about 1.0 to 2.0. For proximal cancer, the MF IRR was consistently <1.5; among American Indian/Alaska Natives, it was <1.0 across all ages. The MF IRRs for CRC vary markedly according to subsite and age but less by racial/ethnic group. These findings may partially reflect differences in screening experiences and access to medical care but also suggest that etiologic factors may be playing a role. C1 [Murphy, Gwen; Cross, Amanda J.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. [Devesa, Susan S.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. [Inskip, Peter D.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. [McGlynn, Katherine A.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. RP Murphy, G (reprint author), NCI, Nutr Epidemiol Branch, DCEG, 6120 Execut Blvd,EPS 3034, Rockville, MD 20892 USA. EM murphygw@mail.nih.gov RI Cook, Michael/A-5641-2009; Murphy, Gwen/G-7443-2015 OI Cook, Michael/0000-0002-0533-7302; FU Intramural Research Program; Division of Cancer Epidemiology and Genetics; National Cancer Institute, NIH; Department of Health and Human Services FX Grant sponsor: Intramural Research Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services NR 43 TC 53 Z9 54 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD APR 1 PY 2011 VL 128 IS 7 BP 1668 EP 1675 DI 10.1002/ijc.25481 PG 8 WC Oncology SC Oncology GA 718XI UT WOS:000287159400017 PM 20503269 ER PT J AU Buchsbaum, BR Padmanabhan, A Berman, KF AF Buchsbaum, Bradley R. Padmanabhan, Aarthi Berman, Karen Faith TI The Neural Substrates of Recognition Memory for Verbal Information: Spanning the Divide between Short- and Long-term Memory SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID VENTROLATERAL PREFRONTAL CORTEX; MEDIAL TEMPORAL-LOBE; WORKING-MEMORY; REPETITION SUPPRESSION; RETRIEVAL-PROCESSES; PARIETAL CORTEX; SERIAL-RECALL; AREA SPT; BRAIN; FMRI AB One of the classic categorical divisions in the history of memory research is that between short-term and long-term memory. Indeed, because memory for the immediate past (a few seconds) and memory for the relatively more remote past (several seconds and beyond) are assumed to rely on distinct neural systems, more often than not, memory research has focused either on short- (or "working memory") or on long-term memory. Using an auditory-verbal continuous recognition paradigm designed for fMRI, we examined how the neural signatures of recognition memory change across an interval of time (from 2.5 to 30 sec) that spans this hypothetical division between short-and long-term memory. The results revealed that activity during successful auditory-verbal item recognition in inferior parietal cortex and the posterior superior temporal lobe was maximal for early lags, whereas, conversely, activity in the left inferior frontal gyrus increased as a function of lag. Taken together, the results reveal that as the interval between item repetitions increases, there is a shift in the distribution of memory-related activity that moves from posterior temporoparietal cortex (lags 1-4) to inferior frontal regions (lags 5-10), indicating that as time advances, the burden of recognition memory is increasingly placed on top-down retrieval mechanisms that are mediated by structures in inferior frontal cortex. C1 [Buchsbaum, Bradley R.; Padmanabhan, Aarthi; Berman, Karen Faith] NIMH, Bethesda, MD 20892 USA. RP Buchsbaum, BR (reprint author), Baycrest Hosp, Rotman Res Inst, 3560 Bathurst St, Toronto, ON M6A 2E1, Canada. EM bbuchsbaum@rotman-baycrest.on.ca FU Intramural NIH HHS [ZIA MH002717-17] NR 77 TC 9 Z9 9 U1 4 U2 15 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD APR PY 2011 VL 23 IS 4 BP 978 EP 991 DI 10.1162/jocn.2010.21496 PG 14 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 699WF UT WOS:000285692900017 PM 20350181 ER PT J AU Aronova, MA Sousa, AA Leapman, RD AF Aronova, M. A. Sousa, A. A. Leapman, R. D. TI EELS characterization of radiolytic products in frozen samples SO MICRON LA English DT Review DE Electron energy loss spectroscopy; EELS; Radiation damage; Biological applications; Molecular oxygen; Frozen samples; Cryo-electron microscopy; Electron tomography ID ENERGY-LOSS SPECTROSCOPY; CRYO-ELECTRON MICROSCOPY; HYDRATED SOFT MATERIALS; RADIATION-DAMAGE; BIOLOGICAL MOLECULES; WATER; SPECIMENS; DIFFRACTION; RESOLUTION; SECTIONS AB Electron energy loss spectroscopy (EELS) was used to obtain information about the radiation chemistry of frozen aqueous specimens in the electron microscope by observing the hydrogen and oxygen K-edges. Measurements on frozen solutions of 30% hydrogen peroxide revealed the presence of molecular oxygen identified by a distinct 531-eV peak at the O K-edge even for electron doses below 100 e/nm(2). The molecular oxygen content of irradiated H(2)O(2) solution was determined by least squares fitting of O K-edge reference spectra from water and gas-phase oxygen. It was found that the fraction of molecular oxygen to water oxygen was in the range 0.03-0.05. EELS from pure frozen water showed no features attributable to molecular oxygen or molecular hydrogen (K edge at similar to 13 eV) even at high electron doses above 10(5) e/nm(2). Spectra from frozen sucrose and protein solutions and their mixtures, however, did show evolution of a molecular hydrogen peak at similar to 13 eV for doses above 10(5) e/nm(2), consistent with previous measurements and indicative of hydrogen bubble formation. Molecular oxygen was not observed in any of the frozen solutions of organic compounds indicating that oxygen is not a major product of free radical decay, in contrast to molecular hydrogen formation. Published by Elsevier Ltd. C1 [Aronova, M. A.; Sousa, A. A.; Leapman, R. D.] Natl Inst Biomed Imaging & Bioengn, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA. RP Leapman, RD (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Cellular Imaging & Macromol Biophys, NIH, Bldg 13,Room 3N17,13 S Dr, Bethesda, MD 20892 USA. EM leapmanr@mail.nih.gov FU National Institute of Biomedical Imaging and Bioengineering at the National Institutes of Heath FX We thank Prof. J. Dubochet for raising the question about whether or not molecular oxygen is a byproduct of radiation damage in frozen hydrated specimens. This work was supported by the intramural program of the National Institute of Biomedical Imaging and Bioengineering at the National Institutes of Heath. NR 32 TC 14 Z9 14 U1 1 U2 34 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-4328 J9 MICRON JI Micron PD APR PY 2011 VL 42 IS 3 BP 252 EP 256 DI 10.1016/j.micron.2010.10.009 PG 5 WC Microscopy SC Microscopy GA 716JK UT WOS:000286964700004 PM 21111626 ER PT J AU Ausavarat, S Tongkobpetch, S Praphanphoj, V Mahatumarat, C Rojvachiranonda, N Snabboon, T Markello, TC Gahl, WA Suphapeetiporn, K Shotelersuk, V AF Ausavarat, Surasawadee Tongkobpetch, Siraprapa Praphanphoj, Verayuth Mahatumarat, Charan Rojvachiranonda, Nond Snabboon, Thiti Markello, Thomas C. Gahl, William A. Suphapeetiporn, Kanya Shotelersuk, Vorasuk TI PTPRF is disrupted in a patient with syndromic amastia SO BMC MEDICAL GENETICS LA English DT Article DE amastia athelia; development of breasts and nipples; ectodermal dysplasia; renal agenesis; balanced chromosome translocation; PTPRF; LAR ID MAMMARY-GLAND DEVELOPMENT; FINLAY-MARKS-SYNDROME; GENE; EXPRESSION; MUTATION; RECEPTOR; BREAST AB Background: The presence of mammary glands distinguishes mammals from other organisms. Despite significant advances in defining the signaling pathways responsible for mammary gland development in mice, our understanding of human mammary gland development remains rudimentary. Here, we identified a woman with bilateral amastia, ectodermal dysplasia and unilateral renal agenesis. She was found to have a chromosomal balanced translocation, 46, XX,t(1;20)(p34.1;q13.13). In addition to characterization of her clinical and cytogenetic features, we successfully identified the interrupted gene and studied its consequences. Methods: Characterization of the breakpoints was performed by molecular cytogenetic techniques. The interrupted gene was further analyzed using quantitative real-time PCR and western blotting. Mutation analysis and high-density SNP array were carried out in order to find a pathogenic mutation. Allele segregations were obtained by haplotype analysis. Results: We enabled to identify its breakpoint on chromosome 1 interrupting the protein tyrosine receptor type F gene (PTPRF). While the patient's mother and sisters also harbored the translocated chromosome, their non-translocated chromosomes 1 were different from that of the patient. Although a definite pathogenic mutation on the paternal allele could not be identified, PTPRF's RNA and protein of the patient were significantly less than those of her unaffected family members. Conclusions: Although ptprf has been shown to involve in murine mammary gland development, no evidence has incorporated PTPRF in human organ development. We, for the first time, demonstrated the possible association of PTPRF with syndromic amastia, making it a prime candidate to investigate for its spatial and temporal roles in human breast development. C1 [Ausavarat, Surasawadee; Tongkobpetch, Siraprapa; Suphapeetiporn, Kanya; Shotelersuk, Vorasuk] Chulalongkorn Univ, Fac Med, Ctr Excellence Med Genet, Dept Pediat, Bangkok 10330, Thailand. [Ausavarat, Surasawadee] Chulalongkorn Univ, Fac Grad Sch, Interdept Biomed Sci, Bangkok 10330, Thailand. [Ausavarat, Surasawadee; Tongkobpetch, Siraprapa; Suphapeetiporn, Kanya; Shotelersuk, Vorasuk] King Chulalongkorn Mem Hosp, Mol Genet Diagnost Ctr, Bangkok 10330, Thailand. [Praphanphoj, Verayuth] Rajanukul Inst, Med Genet Res Ctr, Bangkok 10400, Thailand. [Mahatumarat, Charan; Rojvachiranonda, Nond] Chulalongkorn Univ, Fac Med, Dept Surg, Bangkok 10330, Thailand. [Snabboon, Thiti] Chulalongkorn Univ, Dept Internal Med, Fac Med, Bangkok 10330, Thailand. [Markello, Thomas C.; Gahl, William A.] NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Suphapeetiporn, K (reprint author), Chulalongkorn Univ, Fac Med, Ctr Excellence Med Genet, Dept Pediat, Bangkok 10330, Thailand. EM Kanya.Su@chula.ac.th FU Royal Golden Jubilee Ph.D. Program [PHD/0013/2548]; Thailand Research Fund; National Science and Technology Development Agency; Chulalongkorn University; National Research University [HR1163A]; National Human Genome Research Institute FX We thank Ms. Supranee Buranapraditkun of the Faculty of Medicine, Chulalongkorn University for technical assistance in EBV-transformed cell lines and Dr. David Adams of the National Human Genome Research Institute, National Institutes of Health, USA, for the interpretation of the array results. This study was supported by the Royal Golden Jubilee Ph.D. Program to SA (Grant No. PHD/0013/2548), the Thailand Research Fund, National Science and Technology Development Agency, the 90th Anniversary of the Chulalongkorn University fund, the National Research University Project of CHE and the Ratchadapiseksomphot Endowment Fund (HR1163A), and the Intramural Research Program of the National Human Genome Research Institute. NR 13 TC 4 Z9 4 U1 1 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2350 J9 BMC MED GENET JI BMC Med. Genet. PD MAR 31 PY 2011 VL 12 AR 46 DI 10.1186/1471-2350-12-46 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 755AX UT WOS:000289900100001 PM 21453473 ER PT J AU Lie, RK Miller, FG AF Lie, Reidar K. Miller, Franklin G. TI What counts as reliable evidence for public health policy: the case of circumcision for preventing HIV infection SO BMC MEDICAL RESEARCH METHODOLOGY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; MEN; PRINCIPLES; EQUIPOISE; BENEFIT; KENYA AB Background: There is an ongoing controversy over the relative merits of randomized controlled trials (RCTs) and non-randomized observational studies in assessing efficacy and guiding policy. In this paper we examine male circumcision to prevent HIV infection as a case study that can illuminate the appropriate role of different types of evidence for public health interventions. Discussion: Based on an analysis of two Cochrane reviews, one published in 2003 before the results of three RCTs, and one in 2009, we argue that if we rely solely on evidence from RCTs and exclude evidence from well-designed non-randomized studies, we limit our ability to provide sound public health recommendations. Furthermore, the bias in favor of RCT evidence has delayed research on policy relevant issues. Summary: This case study of circumcision and HIV prevention demonstrates that if we rely solely on evidence from RCTs and exclude evidence from well-designed non-randomized studies, we limit our ability to provide sound public health recommendations. C1 [Lie, Reidar K.; Miller, Franklin G.] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Lie, RK (reprint author), NIH, Dept Bioeth, Ctr Clin, 10 Ctr Dr, Bethesda, MD 20892 USA. EM rlie@cc.nih.gov FU NIH Clinical Center FX This research was supported by the Intramural Research Program of the NIH Clinical Center. The opinions expressed are the author's own. They do not reflect any position or policy of the National Institutes of Health, Public Health Service, or Department of Health and Human Services. We would like to thank Steve Pearson and Asbjorn Hrobjartsson for helpful comments on earlier drafts of the paper. NR 25 TC 5 Z9 5 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2288 J9 BMC MED RES METHODOL JI BMC Med. Res. Methodol. PD MAR 31 PY 2011 VL 11 AR 34 DI 10.1186/1471-2288-11-34 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 752GJ UT WOS:000289679100003 PM 21453535 ER PT J AU Kmieciak, M Payne, KK Idowu, MO Grimes, MM Graham, L Ascierto, ML Wang, E Wang, XY Bear, HD Manjili, MH AF Kmieciak, Maciej Payne, Kyle K. Idowu, Michael O. Grimes, Margaret M. Graham, Laura Ascierto, Maria-Libera Wang, Ena Wang, Xiang-Yang Bear, Harry D. Manjili, Masoud H. TI Tumor escape and progression of HER-2/neu negative breast cancer under immune pressure SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Article ID IFN-GAMMA; IN-SITU; CELLS; LYMPHOCYTES; AMPLIFICATION; TRANSITION; EXPRESSION; CARCINOMA; RESPONSES; ANTIGEN AB Background: Emerging data from pre-clinical and clinical studies suggest that HER-2/neu-specific T cell responses could induce HER-2/neu antigen loss in the tumor cells. These data suggest that patients with HER-2/neu negative breast cancer might have had HER-2/neu positive premalignant lesions in the past that progressed to HER-2/neu negative breast cancer under HER-2/neu-specific immune pressure. Methods: We conducted a pilot study in patients with HER-2/neu positive and HER-2/neu negative breast cancers as well as a patient with ductal carcinoma in situ (DCIS). HER-2/neu expression was determined by FISH. HER-2/neu-specific T cell responses were determined by using IFN-gamma ELISA. Expression of IFN-gamma R alpha in the tumors was determined by immunohistochemistry analysis of paraffin-embedded tissues. Results: We determined that majority of (10 of 12) patients with HER-2/neu negative breast cancer had HER-2/neu-specific IFN-gamma producing T cell responses which was stronger than those in patients with HER-2/neu positive tumors. Such immune responses were associated with nuclear translocation of IFN-gamma R alpha in their tumor cells. Patient with DCIS also showed HER-2/neu-specific T cell responses. Conclusion: These data suggest that conducting retrospective studies in patients with HER-2/neu negative breast cancers and prospective studies in patients with HER-2/neu positive DCIS can determine whether HER-2/neu negative invasive carcinomas arise from HER-2/neu positive DCIS under the immune pressure. C1 [Kmieciak, Maciej; Payne, Kyle K.; Manjili, Masoud H.] Virginia Commonwealth Univ, Massey Canc Ctr, Dept Microbiol & Immunol, Richmond, VA 23298 USA. [Idowu, Michael O.; Grimes, Margaret M.] Virginia Commonwealth Univ, Massey Canc Ctr, Dept Pathol, Richmond, VA USA. [Graham, Laura; Bear, Harry D.] Virginia Commonwealth Univ, Massey Canc Ctr, Dept Surg, Richmond, VA USA. [Ascierto, Maria-Libera; Wang, Ena] NIH, IDIS, Dept Transfus Med, Clin Ctr & Ctr Human Immunol CHI, Bethesda, MD 20892 USA. [Wang, Xiang-Yang] Virginia Commonwealth Univ, IDIS, Dept Human & Mol Genet, Richmond, VA 23298 USA. RP Manjili, MH (reprint author), Virginia Commonwealth Univ, Massey Canc Ctr, Dept Microbiol & Immunol, 401 Coll St, Richmond, VA 23298 USA. EM mmanjili@vcu.edu RI Ascierto, Maria Libera/A-9239-2012; OI Payne, Kyle/0000-0002-6531-9835 FU Massey Cancer Center [2006FPP-04]; VCU [145820] FX This work was supported by Massey Cancer Center Pilot Project Program 2006FPP-04 (M. H. Manjili) and VCU Presidential Research Incentive Program 145820 (M. H. Manjili). We also thank Dr. Elizabeth Bolesta for helping with the expression of the recombinant proteins. NR 18 TC 11 Z9 12 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 MAR 31 PY 2011 VL 9 AR 35 DI 10.1186/1479-5876-9-35 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 749PC UT WOS:000289479800001 PM 21453513 ER PT J AU Smith, ST Chadwick, RS AF Smith, Sonya T. Chadwick, Richard S. TI Simulation of the Response of the Inner Hair Cell Stereocilia Bundle to an Acoustical Stimulus SO PLOS ONE LA English DT Article ID IMMERSED BOUNDARY METHOD; MECHANOELECTRICAL TRANSDUCTION; CHANNELS; FORCES; MOTION; SPEED AB Mammalian hearing relies on a cochlear hydrodynamic sensor embodied in the inner hair cell stereocilia bundle. It is presumed that acoustical stimuli induce a fluid shear-driven motion between the tectorial membrane and the reticular lamina to deflect the bundle. It is hypothesized that ion channels are opened by molecular gates that sense tension in tip-links, which connect adjacent stepped rows of stereocilia. Yet almost nothing is known about how the fluid and bundle interact. Here we show using our microfluidics model how each row of stereocilia and their associated tip links and gates move in response to an acoustical input that induces an orbital motion of the reticular lamina. The model confirms the crucial role of the positioning of the tectorial membrane in hearing, and explains how this membrane amplifies and synchronizes the timing of peak tension in the tip links. Both stereocilia rotation and length change are needed for synchronization of peak tip link tension. Stereocilia length change occurs in response to accelerations perpendicular to the oscillatory fluid shear flow. Simulations indicate that nanovortices form between rows to facilitate diffusion of ions into channels, showing how nature has devised a way to solve the diffusive mixing problem that persists in engineered microfluidic devices. C1 [Smith, Sonya T.] Howard Univ, Dept Mech Engn, Washington, DC 20059 USA. [Smith, Sonya T.; Chadwick, Richard S.] Natl Inst Deafness & Other Commun Disorders, Sect Auditory Mech, NIH, Bethesda, MD USA. RP Smith, ST (reprint author), Howard Univ, Dept Mech Engn, Washington, DC 20059 USA. EM chadwick@helix.nih.gov FU National Institute on Deafness and Other Communication Disorders [DC00033-15]; ORISE fellowship through the NIDCD FX This work was supported by the intramural program project DC00033-15 in the National Institute on Deafness and Other Communication Disorders. STS' sabbatical was funded as an ORISE fellowship through the NIDCD. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 18 TC 8 Z9 8 U1 2 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 31 PY 2011 VL 6 IS 3 AR e18161 DI 10.1371/journal.pone.0018161 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 743YU UT WOS:000289057200035 PM 21483823 ER PT J AU Um, JH Pendergast, JS Springer, DA Foretz, M Viollet, B Brown, A Kim, MK Yamazaki, S Chung, JH AF Um, Jee-Hyun Pendergast, Julie S. Springer, Danielle A. Foretz, Marc Viollet, Benoit Brown, Alexandra Kim, Myung K. Yamazaki, Shin Chung, Jay H. TI AMPK Regulates Circadian Rhythms in a Tissue- and Isoform-Specific Manner SO PLOS ONE LA English DT Article ID ACTIVATED PROTEIN-KINASE; MOUSE PERIPHERAL-TISSUES; SKELETAL-MUSCLE; SUPRACHIASMATIC NUCLEUS; GENE-EXPRESSION; ADIPOSE-TISSUE; PPAR-GAMMA; FOOD-INTAKE; MITOCHONDRIAL BIOGENESIS; CALORIE RESTRICTION AB Background: AMP protein kinase (AMPK) plays an important role in food intake and energy metabolism, which are synchronized to the light-dark cycle. In vitro, AMPK affects the circadian rhythm by regulating at least two clock components, CKI alpha and CRY1, via direct phosphorylation. However, it is not known whether the catalytic activity of AMPK actually regulates circadian rhythm in vivo. Methodology/Principal Finding: The catalytic subunit of AMPK has two isoforms: alpha 1 and alpha 2. We investigate the circadian rhythm of behavior, physiology and gene expression in AMPK alpha 1-/- and AMPK alpha 2-/- mice. We found that both alpha 1-/- and alpha 2-/- mice are able to maintain a circadian rhythm of activity in dark-dark (DD) cycle, but alpha 1-/- mice have a shorter circadian period whereas alpha 2-/- mice showed a tendency toward a slightly longer circadian period. Furthermore, the circadian rhythm of body temperature was dampened in alpha 1-/- mice, but not in alpha 2-/- mice. The circadian pattern of core clock gene expression was severely disrupted in fat in alpha 1-/- mice, but it was severely disrupted in the heart and skeletal muscle of alpha 2-/- mice. Interestingly, other genes that showed circadian pattern of expression were dysreguated in both alpha 1-/- and alpha 2-/- mice. The circadian rhythm of nicotinamide phosphoryl-transferase (NAMPT) activity, which converts nicotinamide (NAM) to NAD(+), is an important regulator of the circadian clock. We found that the NAMPT rhythm was absent in AMPK-deficient tissues and cells. Conclusion/Significance: This study demonstrates that the catalytic activity of AMPK regulates circadian rhythm of behavior, energy metabolism and gene expression in isoform-and tissue-specific manners. C1 [Um, Jee-Hyun; Brown, Alexandra; Kim, Myung K.; Chung, Jay H.] NHLBI, Lab Obes & Aging Res, Genet & Dev Biol Ctr, NIH, Bethesda, MD 20892 USA. [Pendergast, Julie S.; Yamazaki, Shin] Vanderbilt Univ, Dept Biol Sci, Nashville, TN USA. [Springer, Danielle A.] NHLBI, Mouse Phenotyping Core Facil, NIH, Bethesda, MD 20892 USA. [Foretz, Marc; Viollet, Benoit] Univ Paris 05, Inst Cochin, CNRS, UMR 8104, Paris, France. [Foretz, Marc; Viollet, Benoit] INSERM, U567, Paris, France. RP Um, JH (reprint author), NHLBI, Lab Obes & Aging Res, Genet & Dev Biol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. EM chungj@nhlbi.nih.gov FU National Heart Lung and Blood Institute, National Institutes of Health FX This work was supported by the Intramural Research Program, National Heart Lung and Blood 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 61 TC 43 Z9 47 U1 2 U2 13 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 31 PY 2011 VL 6 IS 3 AR e18450 DI 10.1371/journal.pone.0018450 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 743YU UT WOS:000289057200081 PM 21483791 ER PT J AU Lee, YN Brandal, S Noel, P Wentzel, E Mendell, JT McDevitt, MA Kapur, R Carter, M Metcalfe, DD Takemoto, CM AF Lee, Youl-Nam Brandal, Stephanie Noel, Pierre Wentzel, Erik Mendell, Joshua T. McDevitt, Michael A. Kapur, Reuben Carter, Melody Metcalfe, Dean D. Takemoto, Clifford M. TI KIT signaling regulates MITF expression through miRNAs in normal and malignant mast cell proliferation SO BLOOD LA English DT Article ID RECEPTOR TYROSINE KINASE; C-KIT; TRANSCRIPTION FACTOR; GENE-EXPRESSION; GROWTH-FACTOR; MASTOCYTOSIS; MICROPHTHALMIA; ACTIVATION; MUTATION; LOCUS AB Activating mutations in codon D816 of the tyrosine kinase receptor, KIT, are found in the majority of patients with systemic mastocytosis. We found that the transcription factor, microphthalmia-associated transcription factor (MITF), is highly expressed in bone marrow biopsies from 9 of 10 patients with systemic mastocytosis and activating c-KIT mutations. In primary and transformed mast cells, we show that KIT signaling markedly up-regulates MITF protein. We demonstrate that MITF is required for the proliferative phenotype by inhibiting colony-forming units with sh-RNA knockdown of MITF. Furthermore, constitutively active KIT does not restore growth of primary MITF-deficient mast cells. MITF mRNA levels do not change significantly with KIT signaling, suggesting posttran-scriptional regulation. An array screen from mast cells identified candidate miRNAs regulated by KIT signaling. We found that miR-539 and miR-381 are down-regulated by KIT signaling and they repressed MITF expression through con-served miRNA binding sites in the MITF 3'-untranslated region. Forced expression of these miRNAs suppressed MITF protein and inhibited colony-forming capacity of mastocytosis cell lines. This work demonstrates a novel regulatory pathway between 2 critical mast cell factors, KIT and MITF, mediated by miRNAs; dysregulation of this pathway may contribute to abnormal mast cell proliferation and malignant mast cell diseases. (Blood. 2011;117(13):3629-3640) C1 [Takemoto, Clifford M.] Johns Hopkins Univ, Div Pediat Hematol, Baltimore, MD 21205 USA. [Noel, Pierre] NIH, Dept Lab Med, Bethesda, MD 20892 USA. [Wentzel, Erik; Mendell, Joshua T.] Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA. [Wentzel, Erik; Mendell, Joshua T.] Johns Hopkins Univ, Sch Med, Inst Genet Med, Baltimore, MD 21205 USA. [Kapur, Reuben] Indiana Univ, Sch Med, Herman B Wells Ctr Pediat Res, Indianapolis, IN USA. [Carter, Melody; Metcalfe, Dean D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Takemoto, CM (reprint author), Johns Hopkins Univ, Div Pediat Hematol, 720 Rutland Ave,Ross 1125, Baltimore, MD 21205 USA. EM ctakemot@jhmi.edu FU March of Dimes Birth Defects Foundation [5-FY04-30]; Children's Cancer Foundation; National Institutes of Health [5R01HL077178, 4R01HL077177, 2R01HL08111]; National Institute of Allergy and Infectious Diseases; HHMI Early Career Scientist FX This work was supported by in part by the March of Dimes Birth Defects Foundation (Basil O'Conner Starter Scholar Research Award grant 5-FY04-30; C. M. T.), a Children's Cancer Foundation Grant (C. M. T.), the National Institutes of Health (grant 5R01HL077178, C. M. T.; grants 4R01HL077177 and 2R01HL08111, R. K.), and the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (D. D. M., M. C.). J.T.M. is an HHMI Early Career Scientist. NR 34 TC 26 Z9 30 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 31 PY 2011 VL 117 IS 13 BP 3629 EP 3640 DI 10.1182/blood-2010-07-293548 PG 12 WC Hematology SC Hematology GA 743EH UT WOS:000288999800021 PM 21273305 ER PT J AU Kamata, T Bong, YS Mood, K Park, MJ Nishanian, TG Lee, HS AF Kamata, Teddy Bong, Yong-Sik Mood, Kathleen Park, Mae Ja Nishanian, Tagvor G. Lee, Hyun-Shik TI EphrinB1 interacts with the transcriptional co-repressor Groucho/xTLE4 SO BMB REPORTS LA English DT Article DE Eph; EphrinB1; Groucho; Xenopus; xTLE4 ID TRANSMEMBRANE LIGANDS; XENOPUS-LAEVIS; PHOSPHORYLATION; COREPRESSOR; RECEPTOR; PROTEIN; FAMILY; DOMAIN; GENE; DIFFERENTIATION AB Ephrin signaling is involved in various morphogenetic events, such as axon guidance, hindbrain segmentation, and angiogenesis. We conducted a yeast two-hybrid screen using the intracellular domain (ICD) of EphrinB1 to gain biochemical insight into the function of the EphrinB1 ICD. We identified the transcriptional co-repressor xTLE1/Groucho as an EphrinB1 interacting protein. Whole-mount in situ hybridization of Xenopus embryos confirmed the co-localization of EphrinB1 and a Xenopus counterpart to TLE1, xTLE4, during various stages of development The EphrinB1/xTLE4 interaction was confirmed by co-immunoprecipitation experiments. Further characterization of the interaction revealed that the carboxy-terminal PDZ binding motif of EphrinB1 and the SP domain of xTLE4 are required for binding. Additionally, phosphorylation of EphrinB1 by a constitutively activated fibroblast growth factor receptor resulted in loss of the interaction, suggesting that the interaction is modulated by tyrosine phosphorylation of the EphrinB1 ICD. [BMB reports 2011; 44(3): 199-204] C1 [Kamata, Teddy; Bong, Yong-Sik; Mood, Kathleen; Nishanian, Tagvor G.; Lee, Hyun-Shik] NCI, Lab Cell & Dev Signaling, Frederick, MD 21702 USA. [Park, Mae Ja] Kyungpook Natl Univ, Dept Anat, Sch Med, Taegu 700422, South Korea. [Lee, Hyun-Shik] Kyungpook Natl Univ, Sch Life Sci, Coll Nat Sci, Taegu 702701, South Korea. RP Lee, HS (reprint author), NCI, Lab Cell & Dev Signaling, Frederick, MD 21702 USA. EM tagvor@jertag.com; leeh@knu.ac.kr RI Lee, Hyun-Shik/G-3555-2011 FU Korean Government (MOEHRD) [KRF-2005-041-E00012]; Ministry for Health, Welfare & Family Affairs, Republic of Korea [A100335] FX This work was supported by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD) (KRF-2005-041-E00012) and a grant of the Korean Health Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (A100335). NR 32 TC 2 Z9 8 U1 0 U2 2 PU KOREAN SOCIETY BIOCHEMISTRY & MOLECULAR BIOLOGY PI SEOUL PA KOREA SCIENCE & TECHNOLOGY CENTER, # 801, 635-4 , YEOKSAM-DONG, KANGNAM-KU, SEOUL, 135-703, SOUTH KOREA SN 1976-6696 J9 BMB REP JI BMB Rep. PD MAR 31 PY 2011 VL 44 IS 3 BP 199 EP 204 DI 10.5483/BMBRep.2011.44.3.199 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 743WW UT WOS:000289051000009 PM 21429299 ER PT J AU Yewdell, JW Dolan, BP AF Yewdell, Jonathan W. Dolan, Brian P. TI IMMUNOLOGY Cross-dressers turn on T cells SO NATURE LA English DT Editorial Material ID DENDRITIC CELLS C1 [Yewdell, Jonathan W.; Dolan, Brian P.] NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. EM jyewdell@niaid.nih.gov RI yewdell, jyewdell@nih.gov/A-1702-2012 FU Intramural NIH HHS [ZIA AI000542-23] NR 8 TC 7 Z9 7 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 31 PY 2011 VL 471 IS 7340 BP 581 EP 582 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 742NN UT WOS:000288951200025 PM 21455165 ER PT J AU Gottesman, S AF Gottesman, Susan TI MICROBIOLOGY Dicing defence in bacteria SO NATURE LA English DT Editorial Material ID CRISPR; PROKARYOTES; ARCHAEA; RNAS C1 NCI, Mol Biol Lab, Bethesda, MD 20892 USA. RP Gottesman, S (reprint author), NCI, Mol Biol Lab, Bldg 37, Bethesda, MD 20892 USA. EM susang@helix.nih.gov NR 10 TC 8 Z9 9 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 31 PY 2011 VL 471 IS 7340 BP 588 EP 589 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 742NN UT WOS:000288951200031 PM 21455171 ER PT J AU Ross, JL Quigley, CA Cao, DC Feuillan, P Kowal, K Chipman, JJ Cutler, GB AF Ross, Judith L. Quigley, Charmian A. Cao, Dachuang Feuillan, Penelope Kowal, Karen Chipman, John J. Cutler, Gordon B., Jr. TI Growth Hormone plus Childhood Low-Dose Estrogen in Turner's Syndrome SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ADULT HEIGHT; FINAL HEIGHT; ETHINYL ESTRADIOL; SHORT-TERM; GIRLS; THERAPY; CHILDREN; MANAGEMENT; WOMEN; DEFICIENCY AB BACKGROUND Short stature and ovarian failure are characteristic features of Turner's syndrome. Although recombinant human growth hormone is commonly used to treat the short stature associated with this syndrome, a randomized, placebo-controlled trial is needed to document whether such treatment increases adult height. Furthermore, it is not known whether childhood estrogen replacement combined with growth hormone therapy provides additional benefit. We examined the independent and combined effects of growth hormone and early, ultra-low-dose estrogen on adult height in girls with Turner's syndrome. METHODS In this double-blind, placebo-controlled trial, we randomly assigned 149 girls, 5.0 to 12.5 years of age, to four groups: double placebo (placebo injection plus childhood oral placebo, 39 patients), estrogen alone (placebo injection plus childhood oral low-dose estrogen, 40), growth hormone alone (growth hormone injection plus childhood oral placebo, 35), and growth hormone-estrogen (growth hormone injection plus childhood oral low-dose estrogen, 35). The dose of growth hormone was 0.1 mg per kilogram of body weight three times per week. The doses of ethinyl estradiol (or placebo) were adjusted for chronologic age and pubertal status. At the first visit after the age of 12.0 years, patients in all treatment groups received escalating doses of ethinyl estradiol. Growth hormone injections were terminated when adult height was reached. RESULTS The mean standard-deviation scores for adult height, attained at an average age of 17.0 +/- 1.0 years, after an average study period of 7.2 +/- 2.5 years were -2.81 +/- 0.85, -3.39 +/- 0.74, -2.29 +/- 1.10, and -2.10 +/- 1.02 for the double-placebo, estrogen-alone, growth hormone-alone, and growth hormone-estrogen groups, respectively (P<0.001). The overall effect of growth hormone treatment (vs. placebo) on adult height was a 0.78 +/- 0.13 increase in the height standard-deviation score (5.0 cm) (P<0.001); adult height was greater in the growth hormone-estrogen group than in the growth hormone-alone group, by 0.32 +/- 0.17 standard-deviation score (2.1 cm) (P = 0.059), suggesting a modest synergy between childhood low-dose ethinyl estradiol and growth hormone. CONCLUSIONS Our study shows that growth hormone treatment increases adult height in patients with Turner's syndrome. In addition, the data suggest that combining childhood ultra-low-dose estrogen with growth hormone may improve growth and provide other potential benefits associated with early initiation of estrogen replacement. C1 [Ross, Judith L.] Thomas Jefferson Univ, Jefferson Med Coll, Dept Pediat, Philadelphia, PA 19107 USA. [Ross, Judith L.; Kowal, Karen] Alfred I DuPont Hosp Children, Wilmington, DE USA. [Quigley, Charmian A.; Cao, Dachuang; Chipman, John J.; Cutler, Gordon B., Jr.] Lilly Res Labs, Indianapolis, IN USA. [Feuillan, Penelope; Cutler, Gordon B., Jr.] NICHHD, Bethesda, MD 20892 USA. RP Ross, JL (reprint author), Thomas Jefferson Univ, Jefferson Med Coll, Dept Pediat, 1025 Walnut St, Philadelphia, PA 19107 USA. EM judith.ross@jefferson.edu FU National Institute of Child Health and Human Development; Eli Lilly FX Supported by the National Institute of Child Health and Human Development and Eli Lilly. NR 41 TC 59 Z9 68 U1 1 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 MAR 31 PY 2011 VL 364 IS 13 BP 1230 EP 1242 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 742NO UT WOS:000288951300007 PM 21449786 ER PT J AU Yang, MH Sun, S Kostov, Y Rasooly, A AF Yang, Minghui Sun, Steven Kostov, Yordan Rasooly, Avraham TI A simple 96-well microfluidic chip combined with visual and densitometry detection for resource-poor point of care testing SO SENSORS AND ACTUATORS B-CHEMICAL LA English DT Article DE Lab-on-a-chip; Staphylococcal enterotoxins; Resource-poor; Silver enhancement; Carbon nanotubes; Food safety ID STAPHYLOCOCCAL-ENTEROTOXIN-B; CARBON NANOTUBES; FILM DOSIMETRY; IMMUNOASSAY; LABEL; SCANNERS; IMAGE; ASSAY; FOOD AB There is a well-recognized need for low cost biodetection technologies for resource-poor settings with minimal medical infrastructure. Lab-on-a-chip (LOC) technology has the ability to perform biological assays in such settings. The aim of this work is to develop a low cost, high-throughput detection system for the analysis of 96 samples simultaneously outside the laboratory setting. To achieve this aim, several biosensing elements were combined: a syringe operated ELISA lab-on-a-chip (ELISA-LOC) which integrates fluid delivery system into a miniature 96-well plate: a simplified non-enzymatic reporter and detection approach using a gold nanoparticle-antibody conjugate as a secondary antibody and silver enhancement of the visual signal; and carbon nanotubes (CNT) to increase primary antibody immobilization and improve assay sensitivity. Combined, these elements obviate the need for an ELISA washer, electrical power for operation and a sophisticated detector. We demonstrate the use of the device for detection of Staphylococcal enterotoxin B, a major foodborne toxin using three modes of detection, visual detection, CCD camera and document scanner. With visual detection or using a document scanner to measure the signal, the limit of detection (LOD) was 0.5 ng/ml. In addition to visual detection, for precise quantitation of signal using densitometry and a CCD camera, the LOD was 0.1 ng/ml for the CCD analysis and 0.5 ng/ml for the document scanner. The observed sensitivity is in the same range as laboratory-based ELISA testing. The point of care device can analyze 96 samples simultaneously, permitting high throughput diagnostics in the field and in resource poor areas without ready access to laboratory facilities or electricity. Published by Elsevier B.V. C1 [Sun, Steven; Rasooly, Avraham] US FDA, Div Biol, Off Sci & Engn, Silver Spring, MD 20993 USA. [Yang, Minghui; Sun, Steven; Kostov, Yordan] Univ Maryland Baltimore Cty, Ctr Adv Sensor Technol, Baltimore, MD 21250 USA. [Yang, Minghui] Univ Jinan, Sch Chem & Chem Engn, Jinan 250022, Peoples R China. [Rasooly, Avraham] NCI, Bethesda, MD 20892 USA. RP Rasooly, A (reprint author), US FDA, Div Biol, Off Sci & Engn, 6130 Execut, Silver Spring, MD 20993 USA. EM rasoolya@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 23 TC 13 Z9 13 U1 3 U2 20 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0925-4005 J9 SENSOR ACTUAT B-CHEM JI Sens. Actuator B-Chem. PD MAR 31 PY 2011 VL 153 IS 1 BP 176 EP 181 DI 10.1016/j.snb.2010.10.027 PG 6 WC Chemistry, Analytical; Electrochemistry; Instruments & Instrumentation SC Chemistry; Electrochemistry; Instruments & Instrumentation GA 743LH UT WOS:000289019300026 PM 21503269 ER PT J AU Huang, KP Huang, FL Shetty, PK AF Huang, K. -P. Huang, F. L. Shetty, P. K. TI STIMULATION-MEDIATED TRANSLOCATION OF CALMODULIN AND NEUROGRANIN FROM SOMA TO DENDRITES OF MOUSE HIPPOCAMPAL CA1 PYRAMIDAL NEURONS SO NEUROSCIENCE LA English DT Article DE calmodulin; neurogranin; hippocampus; translocation; dendritic spines; LTP ID PROTEIN-KINASE-C; LONG-TERM POTENTIATION; NULL MUTANT MICE; RAT-BRAIN; SUBSTRATE RC3; SYNAPTIC PLASTICITY; CALCIUM; LOCALIZATION; NUCLEAR; CELLS AB Calmodulin (CaM) and neurogranin (Ng) are two abundant neuronal proteins in the forebrain whose interactions are implicated in the enhancement of synaptic plasticity. To gain further insight into the actions of these two proteins we investigated whether they co-localize in principle neurons and whether they respond to high frequency stimulation in a coordinated fashion. Immunohistochemical staining of CaM and Ng in mouse hippocampal slices revealed that CaM was highly concentrated in the nucleus of CA1 pyramidal neurons, whereas Ng was more broadly localized throughout the soma and dendrites. The asymmetrical localization of CaM in the nucleus of pyramidal neurons was in sharp contrast to the distribution observed in pyramidal cells of the neighboring subiculum, where CaM was uniformly localized throughout the soma and dendrites. The somatic concentrations of CaM and Ng in CA1 pyramidal neurons were approximately 10- and two-fold greater than observed in the dendrites, respectively. High frequency stimulation (HFS) of hippocampal slices promoted mobilization of CaM and Ng from soma to dendrites. These responses were spatially restricted to the area close to the site of stimulation and were inhibited by the N-methyl-D-asparate receptor antagonist 2-amino-5-phosphonopentanoic acid. Furthermore, HFS failed to promote translocation of CaM from soma to dendrites of slices from Ng knockout mice, which also exhibited deficits in HFS-induced long-term potentiation. Trans located CaM and Ng exhibited distinct puncta decorating the apical dendrites of pyramidal neurons and appeared to be concentrated in dendritic spines. These findings suggest that mobilization of CaM and Ng to stimulated dendritic spines may enhance synaptic efficacy by increasing and prolonging the Ca(2+) transients and activation of Ca(2+)/CaM-dependent enzymes. Published by Elsevier Ltd on behalf of IBRO. C1 [Huang, K. -P.; Huang, F. L.; Shetty, P. K.] NICHHD, Program Dev Neurobiol, NIH, Bethesda, MD 20892 USA. RP Huang, KP (reprint author), NICHHD, Program Dev Neurobiol, NIH, Bethesda, MD 20892 USA. EM huangk@mail.nih.gov; fhuang@mail.nih.gov RI SHETTY, PAVAN/B-9804-2012 FU NICHD, NIH FX The research was supported by the Intramural Research Program of the NICHD, NIH. The authors would like to thank Dr. Vincent Schram for his help in con focal microscopy and Dr. Chris McBain for critical reading of the manuscript. NR 40 TC 2 Z9 2 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD MAR 31 PY 2011 VL 178 BP 1 EP 12 DI 10.1016/j.neuroscience.2011.01.027 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 736WK UT WOS:000288525500001 PM 21256930 ER PT J AU Zhu, L Wang, HL Wang, L Wang, Y Jiang, K Li, C Ma, QJ Gao, S Wang, LP Li, W Cai, MJ Wang, HD Niu, G Lee, S Yang, W Fang, XX Chen, XY AF Zhu, Lei Wang, Huiling Wang, Lin Wang, Ye Jiang, Kun Li, Cheng Ma, Qingjie Gao, Shi Wang, Liping Li, Wei Cai, Mingjun Wang, Hongda Niu, Gang Lee, Seulki Yang, Wei Fang, Xuexun Chen, Xiaoyuan TI High-affinity peptide against MT1-MMP for in vivo tumor imaging SO JOURNAL OF CONTROLLED RELEASE LA English DT Article DE Matrix metalloproteinase; MT1-MMP (MMP-14); Phage display peptide library; Near-infrared fluorescence optical imaging ID TYPE-1 MATRIX-METALLOPROTEINASE; INTEGRIN ALPHA(V)BETA(3) EXPRESSION; 1-MATRIX METALLOPROTEINASE; PERICELLULAR PROTEOLYSIS; CELL MIGRATION; PHAGE DISPLAY; MEMBRANE; INVASION; CANCER; IDENTIFICATION AB Membrane type-1 matrix metalloproteinase (MT1-MMP) is a key member of the matrix metalloproteinase (MMP) family. It participates in pericellular proteolysis of extracellular matrix (ECM) macromolecules and is essential for many biological and pathological processes, such as tumor development, angiogenesis and metastasis. A ligand that specifically binds to MT1-MMP may facilitate the labeling of this molecule, allow imaging at the cellular and organism levels, and provide a means for targeted drug delivery specific to MT1-MMP. A non-substrate MT1-MMP binding peptide was identified by screening a Ph.D.-12 (TM) phage display peptide library and conjugated with near-infrared fluorescent (NIRF) dye Cy5.5 for tumor imaging. Peptide HWKHLHNTKTFL (denoted as MT1-AF7p) showed high MT1-MMP binding affinity. Computer modeling verified that MT1-AF7p binds to the MT-loop region of MT1-MMP and interacts with MT1-MMP through hydrogen bonding and hydrophobic interactions. MDA-MB-435 xenografts with high MT1-MMP expression had significantly higher tumor accumulation and better tumor contrast than the low MT1-MMP expressing A549 xenografts after intravenous injection of Cy5.5-MT1-AF7p. Using NIRF imaging, we have demonstrated specific targeting of MT1-AF7p to MT1-MMP-expressing tumors. Thus, MT1-AF7p is an important tool for noninvasive monitoring of MT1-MMP expression in tumors, and it shows great potential as an imaging agent for MT1-MMP-positive tumors. Published by Elsevier B.V. C1 [Cai, Mingjun; Wang, Hongda; Yang, Wei] Chinese Acad Sci, Changchun Inst Appl Chem, State Key Lab Electroanalyt Chem, Changchun 130022, Jilin, Peoples R China. [Zhu, Lei; Wang, Huiling; Wang, Lin; Wang, Ye; Jiang, Kun; Li, Cheng; Fang, Xuexun] Jilin Univ, Minist Educ, Key Lab Mol Enzymol & Enzyme Engn, Changchun 130023, Peoples R China. [Zhu, Lei; Niu, Gang; Lee, Seulki; Chen, Xiaoyuan] NIBIB, LOMIN, NIH, Bethesda, MD 20892 USA. [Zhu, Lei] Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Peoples R China. [Ma, Qingjie; Gao, Shi] Jilin Univ, China Japan Union Hosp, Changchun 130033, Peoples R China. [Wang, Liping; Li, Wei] Jilin Univ, Sch Life Sci, Changchun 130021, Peoples R China. RP Yang, W (reprint author), Chinese Acad Sci, Changchun Inst Appl Chem, State Key Lab Electroanalyt Chem, Changchun 130022, Jilin, Peoples R China. EM yangwei1988@gmail.com; fangxx@jlu.edu.cn; shawn.chen@nih.gov RI Zhu, Lei/P-9786-2016 OI Zhu, Lei/0000-0002-1820-4795 FU Intramural Research Program (IRP); National Institute of Biomedical Imaging and Bioengineering (NIBIB); National Institutes of Health (NIH); National Science Foundation of China [31070669, 81028009]; National High-Tech R&D Program (863 Program) [2009AA03Z309]; China scholarship Council (CSC) FX We thank Dr. Henry S. Eden for proof-reading the manuscript. This work was supported in part by the Intramural Research Program (IRP), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH) and the National Science Foundation of China (Grant No. 31070669 and 81028009) and National High-Tech R&D Program (863 Program, No. 2009AA03Z309). Lei Zhu is partially supported by the scholarship from the China scholarship Council (CSC). NR 44 TC 27 Z9 28 U1 7 U2 41 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-3659 J9 J CONTROL RELEASE JI J. Control. Release PD MAR 30 PY 2011 VL 150 IS 3 BP 248 EP 255 DI 10.1016/j.jconrel.2011.01.032 PG 8 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 771BF UT WOS:000291131500003 PM 21295090 ER PT J AU Menjoge, AR Rinderknecht, AL Navath, RS Faridnia, M Kim, CJ Romero, R Miller, RK Kannan, RM AF Menjoge, Anupa R. Rinderknecht, Amber L. Navath, Raghavendra S. Faridnia, Masoud Kim, Chong J. Romero, Roberto Miller, Richard K. Kannan, Rangaramanujam M. TI Transfer of PAMAM dendrimers across human placenta: Prospects of its use as drug carrier during pregnancy SO JOURNAL OF CONTROLLED RELEASE LA English DT Article DE Biodistribution; Transport; Pharmacokinetic; Drug delivery; Human placenta; Paracellular; Endocytosis ID PERFUSED HUMAN PLACENTA; IN-VITRO; FETAL MEMBRANES; POLY(AMIDOAMINE) DENDRIMERS; IMMUNOGLOBULIN-G; TRANSPORT; PERMEABILITY; DELIVERY; NANOPARTICLES; PEROXIDASE AB Dendrimers offer significant potential as nanocarriers for targeted delivery of drugs and imaging agents. The objectives of this study were to evaluate the transplacental transport, kinetics and biodistribution of PAMAM dendrimers ex-vivo across the human placenta in comparison with antipyrine, a freely diffusible molecule, using dually perfused re-circulating term human placental lobules. The purpose of this study is to determine if dendrimers as drug carriers can be used to design drug delivery systems directed at selectively treating either the mother or the fetus. The transplacental transfers of fluorescently (Alexa 488) tagged PAMAM dendrimer (16 kDa) and antipyrine (188 Da) from maternal to fetal circulation were measured using HPLC/dual UV and fluorescent detector (sensitivity of 10 ng/mL for dendrimer and 100 ng/mL for antipyrine respectively). C(max) for the dendrimer-Alexa (DA) in maternal perfusate (T(max)=15 min) was 18 times higher than in the fetal perfusate and never equilibrated with the maternal perfusate during 5.5 h of perfusion (n = 4). DA exhibited a measurable but low transplacental transport of 2.26 +/- 0.12 mu g/mL during 5.5 h, where the mean transplacental transfer was 0.84 +/- 0.11% of the total maternal concentration and the feto-maternal ratio as percent was 0.073%+/- 0.02. The biochemical and physiological analysis of the placentae perfused with DA demonstrated normal function throughout the perfusion. The immunofluorescence histochemistry confirmed that the biodistribution of DA in perfused placenta was sparsely dispersed, and when noted was principally seen in the inter-villous spaces and outer rim of the villous branches. In a few cases, DA was found internalized and localized in nuclei and cytoplasm of syncytiotrophoblast and inside the villous core; however, DA was mostly absent from the villous capillaries. In conclusion, the PAMAM dendrimers exhibited a low rate of transfer from maternal to the fetal side across the perfused human placenta, which is similar to other investigations of large macromolecules, e.g., IgG. These overall findings suggest that entry of drugs conjugated to polymers, i.e., dendrimers, would be limited in their transfer across the human placenta when compared to smaller drug molecules alone, suggesting novel methods for selectively delivering therapeutics to the pregnant woman without significant transfer to the fetus, especially since the half life of the dendrimer in blood is relatively short. (C) 2010 Elsevier B.V. All rights reserved. C1 [Menjoge, Anupa R.; Navath, Raghavendra S.; Kannan, Rangaramanujam M.] Wayne State Univ, Dept Chem Engn & Mat Sci, Detroit, MI 48202 USA. [Menjoge, Anupa R.; Navath, Raghavendra S.; Kim, Chong J.; Romero, Roberto; Kannan, Rangaramanujam M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Detroit, MI 48201 USA. [Menjoge, Anupa R.; Navath, Raghavendra S.; Kim, Chong J.; Romero, Roberto; Kannan, Rangaramanujam M.] US Dept HHS, Detroit, MI 48201 USA. [Rinderknecht, Amber L.; Faridnia, Masoud; Miller, Richard K.] Univ Rochester, Med Ctr, Dept Obstet & Gynecol, Rochester, NY 14642 USA. RP Kannan, RM (reprint author), Wayne State Univ, Dept Chem Engn & Mat Sci, Detroit, MI 48202 USA. EM rkannan.wsu@gmail.com FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS; NIH [R03 HD059027] FX This study was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS and by the NIH R03 HD059027. We thank Dr. Asad Abbas for help with placental tissue sections. NR 48 TC 44 Z9 47 U1 1 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-3659 J9 J CONTROL RELEASE JI J. Control. Release PD MAR 30 PY 2011 VL 150 IS 3 BP 326 EP 338 DI 10.1016/j.jconrel.2010.11.023 PG 13 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 771BF UT WOS:000291131500012 PM 21129423 ER PT J AU Deterding, LJ Williams, JG Humble, MM Petrovich, RM Wei, SJ Trempus, CS Gates, MB Zhu, F Smart, RC Tennant, RW Tomer, KB AF Deterding, Leesa J. Williams, Jason G. Humble, Margaret M. Petrovich, Robert M. Wei, Sung-Jen Trempus, Carol S. Gates, Matthew B. Zhu, Feng Smart, Robert C. Tennant, Raymond W. Tomer, Kenneth B. TI CD34 antigen: Determination of specific sites of phosphorylation in vitro and in vivo SO INTERNATIONAL JOURNAL OF MASS SPECTROMETRY LA English DT Article DE CD34; Phosphorylation; PKC kinase; AKT2 kinase; LC/MS/MS ID PROTEIN-KINASE-C; CDNA-ENCODING CD34; L-SELECTIN; MURINE CD34; STEM-CELLS; ENRICHMENT; EXPRESSION; SIALOMUCIN; PEPTIDES; MARKER AB CD34, a type I transmembrane glycoprotein, is a surface antigen which is expressed on several cell types, including hematopoietic progenitors, endothelial cells, as well as mast cells. Recently, CD34 has been described as a marker for epidermal stem cells in mouse hair follicles, and is expressed in outer root sheath cells of the human hair follicle. Although the biological function and regulation of CD34 is not well understood, it is thought to be involved in cell adhesion as well as possibly having a role in signal transduction. In addition, CD34 was shown to be critical for skin tumor development in mice, although the exact mechanism remains unknown. Many proteins' functions and biological activities are regulated through post-translational modifications. The extracellular domain of CD34 is heavily glycosylated but the role of these glycans in CD34 function is unknown. Additionally, two sites of tyrosine phosphorylation have been reported on human CD34 and it is known that CD34 is phosphorylated, at least in part, by protein kinase C; however, the precise location of the sites of phosphorylation has not been reported. In an effort to identify specific phosphorylation sites in CD34 and delineate the possible role of protein kinase C, we undertook the identification of the in vitro sites of phosphorylation on the intracellular domain of mouse CD34 (aa 309-382) following PKC treatment. For this work, we are using a combination of enzymatic proteolysis and peptide sequencing by mass spectrometry. After which the in vivo sites of phosphorylation of full-length mouse CD34 expressed from HEK293F cells were determined. The observed in vivo sites of phosphorylation, however, are not consensus PKC sites, but our data indicate that one of these sites may possibly be phosphorylated by AKT2. These results suggest that other kinases, as well as PKC, may have important signaling functions in CD34. Published by Elsevier B.V. C1 [Deterding, Leesa J.; Williams, Jason G.; Petrovich, Robert M.; Gates, Matthew B.; Tomer, Kenneth B.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. [Humble, Margaret M.; Wei, Sung-Jen; Trempus, Carol S.; Tennant, Raymond W.] NIEHS, Lab Pharmacol & Toxicol, NIH, Res Triangle Pk, NC 27709 USA. [Zhu, Feng; Smart, Robert C.] N Carolina State Univ, Cell Signaling & Canc Grp, Dept Environm & Mol Toxicol, Raleigh, NC 27695 USA. RP Deterding, LJ (reprint author), NIEHS, Struct Biol Lab, NIH, POB 12233,MD F0-03, Res Triangle Pk, NC 27709 USA. EM deterdi2@niehs.nih.gov RI Tomer, Kenneth/E-8018-2013 FU NIH, National Institute of Environmental Health Sciences [ES050171] FX This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (ES050171). The authors would like to thank Dr. Allison Schorzman and Dr. Erin Hopper for critical review of this manuscript. NR 30 TC 1 Z9 1 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1387-3806 J9 INT J MASS SPECTROM JI Int. J. Mass Spectrom. PD MAR 30 PY 2011 VL 301 IS 1-3 SI SI BP 12 EP 21 DI 10.1016/j.ijms.2010.05.027 PG 10 WC Physics, Atomic, Molecular & Chemical; Spectroscopy SC Physics; Spectroscopy GA 758TQ UT WOS:000290190000003 PM 21499536 ER PT J AU Roche, B Drake, JM Rohani, P AF Roche, Benjamin Drake, John M. Rohani, Pejman TI An Agent-Based Model to study the epidemiological and evolutionary dynamics of Influenza viruses SO BMC BIOINFORMATICS LA English DT Article ID ENVIRONMENTAL TRANSMISSION; A VIRUS; STOCHASTIC SIMULATION; SURFACE-WATER; WILD BIRDS; ECOLOGY; SYSTEMS; EPIDEMICS; PATTERNS; INVASION AB Background: Influenza A viruses exhibit complex epidemiological patterns in a number of mammalian and avian hosts. Understanding transmission of these viruses necessitates taking into account their evolution, which represents a challenge for developing mathematical models. This is because the phrasing of multi-strain systems in terms of traditional compartmental ODE models either requires simplifying assumptions to be made that overlook important evolutionary processes, or leads to complex dynamical systems that are too cumbersome to analyse. Results: Here, we develop an Individual-Based Model (IBM) in order to address simultaneously the ecology, epidemiology and evolution of strain-polymorphic pathogens, using Influenza A viruses as an illustrative example. Conclusions: We carry out careful validation of our IBM against comparable mathematical models to demonstrate the robustness of our algorithm and the sound basis for this novel framework. We discuss how this new approach can give critical insights in the study of influenza evolution. C1 [Roche, Benjamin; Rohani, Pejman] Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA. [Roche, Benjamin] UMI IRD UPMC 209 UMMISCO, F-93143 Bondy, France. [Drake, John M.] Univ Georgia, Odum Sch Ecol, Athens, GA 30602 USA. [Drake, John M.] Univ Georgia, Ctr Trop & Emerging Global Dis, Athens, GA 30602 USA. [Rohani, Pejman] Univ Michigan, Ctr Study Complex Syst, Ann Arbor, MI 48109 USA. [Rohani, Pejman] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Roche, B (reprint author), Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA. EM benjamin.roche@ird.fr RI Drake, John/D-6622-2012; OI Roche, Benjamin/0000-0001-7975-4232; Drake, John/0000-0003-4646-1235 FU Centers for Disease Control and Prevention [5U19Cl000401]; James S. McDonnell Foundation; National Science Foundation [DEB-0917853]; Science & Technology Directorate, Department of Homeland Security; Fogarty International Center, National Institutes of Health FX This work was supported by the Centers for Disease Control and Prevention (5U19Cl000401), the James S. McDonnell Foundation and the National Science Foundation (DEB-0917853). PR was also supported by the RAPIDD program of the Science & Technology Directorate, Department of Homeland Security, and the Fogarty International Center, National Institutes of Health. NR 40 TC 22 Z9 22 U1 1 U2 27 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 MAR 30 PY 2011 VL 12 AR 87 DI 10.1186/1471-2105-12-87 PG 10 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 751LQ UT WOS:000289619900002 PM 21450071 ER PT J AU Breden, F Lepik, C Longo, NS Montero, M Lipsky, PE Scott, JK AF Breden, Felix Lepik, Christa Longo, Nancy S. Montero, Marinieve Lipsky, Peter E. Scott, Jamie K. TI Comparison of Antibody Repertoires Produced by HIV-1 Infection, Other Chronic and Acute Infections, and Systemic Autoimmune Disease SO PLOS ONE LA English DT Article ID HUMAN MONOCLONAL-ANTIBODIES; MEMORY B-CELLS; VIRUS TYPE-1 GP120; HEAVY-CHAIN; GENE USAGE; NEUTRALIZING ANTIBODIES; EPITOPE-SCAFFOLDS; DEPENDENT ANTIGEN; VACCINE DESIGN; COMBINING SITE AB Background: Antibodies (Abs) produced during HIV-1 infection rarely neutralize a broad range of viral isolates; only eight broadly-neutralizing (bNt) monoclonal (M) Abs have been isolated. Yet, to be effective, an HIV-1 vaccine may have to elicit the essential features of these MAbs. The V genes of all of these bNt MAbs are highly somatically mutated, and the V(H) genes of five of them encode a long (>= 20 aa) third complementarity- determining region (CDR-H3). This led us to question whether long CDR-H3s and high levels of somatic mutation (SM) are a preferred feature of anti-HIV bNt MAbs, or if other adaptive immune responses elicit them in general. Methodology and Principal Findings: We assembled a V(H)-gene sequence database from over 700 human MAbs of known antigen specificity isolated from chronic (viral) infections (ChI), acute (bacterial and viral) infections (AcI), and systemic autoimmune diseases (SAD), and compared their CDR-H3 length, number of SMs and germline V(H)-gene usage. We found that anti-HIV Abs, regardless of their neutralization breadth, tended to have long CDR-H3s and high numbers of SMs. However, these features were also common among Abs associated with other chronic viral infections. In contrast, Abs from acute viral infections (but not bacterial infections) tended to have relatively short CDR-H3s and a low number of SMs, whereas SAD Abs were generally intermediate in CDR-H3 length and number of SMs. Analysis of V(H) gene usage showed that ChI Abs also tended to favor distal germline V(H)-genes (particularly V(H)1-69), especially in Abs bearing long CDR-H3s. Conclusions and Significance: The striking difference between the Abs produced during chronic vs. acute viral infection suggests that Abs bearing long CDR-H3s, high levels of SM and V(H)1-69 gene usage may be preferentially selected during persistent infection. C1 [Breden, Felix] Simon Fraser Univ, Dept Biol Sci, Burnaby, BC V5A 1S6, Canada. [Lepik, Christa; Montero, Marinieve; Scott, Jamie K.] Simon Fraser Univ, Dept Mol Biol & Biochem, Burnaby, BC V5A 1S6, Canada. [Longo, Nancy S.; Lipsky, Peter E.] NIAMSD, Repertoire Anal Grp, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. [Scott, Jamie K.] Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC V5A 1S6, Canada. RP Breden, F (reprint author), Simon Fraser Univ, Dept Biol Sci, Burnaby, BC V5A 1S6, Canada. EM breden@sfu.ca; jkscott@sfu.ca FU National Institutes of Health [AI49111]; Canada Research Chairs; Michael Smith Foundation for Health Research; Natural Sciences and Engineering Research Council of Canada; IRMACS Centre at Simon Fraser University FX This work was supported by National Institutes of Health grant AI49111 (J.K.S.; http://www.nih.gov/), Canada Research Chairs (J.K.S.; http://www.chairs-chaires.gc.ca/), the Michael Smith Foundation for Health Research (M.M.;http://www.msfhr.org/), the Natural Sciences and Engineering Research Council of Canada (C.L., M.M., and F.B.; http://www.nserc-crsng.gc.ca/index_eng.asp), and the IRMACS Centre at Simon Fraser University (http://www.irmacs.ca/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 61 TC 46 Z9 46 U1 0 U2 14 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 30 PY 2011 VL 6 IS 3 AR e16857 DI 10.1371/journal.pone.0016857 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 743YK UT WOS:000289055700006 PM 21479208 ER PT J AU Tao-Cheng, JH Crocker, VT Winters, CA Azzam, R Chludzinski, J Reese, TS AF Tao-Cheng, Jung-Hwa Crocker, Virginia T. Winters, Christine A. Azzam, Rita Chludzinski, John Reese, Thomas S. TI Trafficking of AMPA Receptors at Plasma Membranes of Hippocampal Neurons SO JOURNAL OF NEUROSCIENCE LA English DT Article ID RAT CEREBRAL-CORTEX; DENDRITIC SPINES; NMDA RECEPTORS; GLUTAMATE RECEPTORS; SYNAPTIC PLASTICITY; RECYCLING ENDOSOMES; ENDOCYTIC ZONES; SYNAPSES; INSERTION; SUBUNIT AB The number of AMPA receptors at synapses depends on receptor cycling. Because receptors diffuse rapidly in plasma membranes, their exocytosis and endocytosis need not occur near synapses. Here, pre-embedding immunogold electron microscopy is applied to dissociated rat hippocampal cultures to provide sensitive, high-resolution snapshots of the distribution of surface AMPA receptors in spines, dendrites, and cell bodies that will be informative about trafficking of AMPA receptors. The density of the label for GluR2 varies, but is consistent throughout cell body and dendrites in each individual neuron, except at postsynaptic densities (PSDs), where it is typically higher. Glutamate receptor 2 ( GluR2) labels at PSDs significantly increase after synaptic activation by glycine treatment and increase further upon depolarization by high K(+). Islands of densely packed labels have consistent size and density but vary in frequency under different experimental conditions. These patches of label, which occur on plasma membranes of cell bodies and dendrites but not near PSDs, are taken to be the aftermath of exocytosis of AMPA receptors. A subpopulation of clathrin-coated pits in cell bodies and dendrites label for GluR2, and the number and amount of label in individual pits increase after NMDA treatment. Coated pits near synapses typically lack GluR2 label under basal conditions, but similar to 40% of peri-PSD pits label for GluR2 after NMDA treatment. Thus, exocytosis and endocytosis of AMPA receptors occur mainly at extrasynaptic locations on cell bodies and dendrites. Receptors are not preferentially exocytosed near PSDs, but may be removed via endocytosis at peri-PSD locations after activation of NMDA receptors. C1 [Winters, Christine A.; Chludzinski, John; Reese, Thomas S.] Natl Inst Neurol Disorders & Stroke, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. [Tao-Cheng, Jung-Hwa; Crocker, Virginia T.; Azzam, Rita] Natl Inst Neurol Disorders & Stroke, Electron Microscopy Facil, NIH, Bethesda, MD 20892 USA. RP Reese, TS (reprint author), Natl Inst Neurol Disorders & Stroke, Neurobiol Lab, NIH, 49 Convent Dr,Room 3A60,MSC 4477, Bethesda, MD 20892 USA. EM treese@mbl.edu NR 55 TC 27 Z9 27 U1 0 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 MAR 30 PY 2011 VL 31 IS 13 BP 4834 EP 4843 DI 10.1523/JNEUROSCI.4745-10.2011 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 742JM UT WOS:000288938200009 PM 21451021 ER PT J AU Goldhar, AS Duan, RQ Ginsburg, E Vonderhaar, BK AF Goldhar, Anita S. Duan, Renqin Ginsburg, Erika Vonderhaar, Barbara K. TI Progesterone induces expression of the prolactin receptor gene through cooperative action of Sp1 and C/EBP SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE Prolactin receptor promoter; Prolactin; Progesterone; Mammary ID BREAST-CANCER-CELLS; MAMMARY-GLAND DEVELOPMENT; BINDING-PROTEIN; GROWTH-FACTOR; TRANSCRIPTION FACTORS; PROMOTER USAGE; MESSENGER-RNA; MODULATION; ACTIVATION; ESTROGEN AB Prolactin (Prl) and progesterone (P) cooperate synergistically during mammary gland development and tumorigenesis. We hypothesized that one mechanism for these effects may be through mutual induction of receptors (R). EpH4 mouse mammary epithelial cells stably transfected with PR-A express elevated levels of PrlR mRNA and protein compared to control EpH4 cells that lack the PR. Likewise, T47D human breast cancer cells treated with P overexpress the PrlR and activate PrlR promoter III. PrlR promoter III does not contain a classical P response element but contains several binding sites for transcription proteins, including C/EBP, Sp1 and AP1, which may also interact with the PR. Using promoter deletion and site directed mutagenesis analyses as well as gel shift assays, cooperative activation of the C/EBP and adjacent Sp1A, but not the Sp1B or AP1, sites by P is shown to confer P responsiveness leading to increased PrlR transcription. Published by Elsevier Ireland Ltd. C1 [Goldhar, Anita S.; Duan, Renqin; Ginsburg, Erika; Vonderhaar, Barbara K.] NCI, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Ginsburg, E (reprint author), 37 Convent Dr,Bldg 37,Rm 1106, Bethesda, MD 20892 USA. EM eg20e@nih.gov FU National Cancer Institute FX This research was supported by the Center for Cancer Research, an Intramural Research Program of the National Cancer Institute. NR 51 TC 19 Z9 20 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD MAR 30 PY 2011 VL 335 IS 2 BP 148 EP 157 DI 10.1016/j.mce.2011.01.004 PG 10 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 739PH UT WOS:000288729700008 PM 21238538 ER PT J AU Schneider, WL Damsteegt, VD Stone, AL Kuhlmann, M Bunyard, BA Sherman, DJ Graves, MV Smythers, G Smith, OP Hatziloukas, E AF Schneider, William L. Damsteegt, Vernon D. Stone, Andrew L. Kuhlmann, Micki Bunyard, Britt A. Sherman, Diana J. Graves, Michael V. Smythers, Gary Smith, Oney P. Hatziloukas, Efstathios TI Molecular analysis of soybean dwarf virus isolates in the eastern United States confirms the presence of both D and Y strains and provides evidence of mixed infections and recombination SO VIROLOGY LA English DT Article DE Soybean dwarf virus; Recombination; Mixed infections; Emerging plant virus ID RED-LEAF VIRUS; PLANT-VIRUSES; WHITE CLOVER; IDENTIFICATION; LUTEOVIRUS; HOST; DIVERSITY; DISEASES; ROLL AB Soybean dwarf virus (SbDV), first identified as an agricultural problem in Japan, has emerged as a growing problem in the Midwestern United States. The majority of research on SbDV had been limited to four lab maintained strains from Japan. SbDV had been found in clover in the eastern United States, but these isolates rarely emerged into soybeans. These isolates were analyzed by multiplex PCR and sequencing, revealing that some were infections of both Y and D components, including a recombinant subisolate. Phylogenetic analyses for the US isolates revealed a broad diversity of SbDV, with selection pressure greater on the movement protein than the coat protein. The field isolates from the Eastern United States showed differences in symptoms, aphid transmission and host range, demonstrating that a study of field isolates is an important complement to laboratory maintained strains in understanding the biology and evolution of plant viruses. Published by Elsevier Inc. C1 [Schneider, William L.; Damsteegt, Vernon D.; Stone, Andrew L.; Sherman, Diana J.] USDA ARS, FDWSRU, Ft Detrick, MD 21702 USA. [Kuhlmann, Micki] Univ Maryland, College Pk, MD 20742 USA. [Graves, Michael V.] Univ Massachusetts Lowell, Lowell, MA 01854 USA. [Smythers, Gary] SAIC Inc Frederick, Nci Frederick, MD 21702 USA. [Smith, Oney P.] Hood Coll, Frederick, MD 21701 USA. [Hatziloukas, Efstathios] Aristotle Univ Thessaloniki, GR-54006 Thessaloniki, Greece. RP Schneider, WL (reprint author), USDA ARS, FDWSRU, 1301 Ditto Ave, Ft Detrick, MD 21702 USA. EM william.schneider@ars.usda.gov NR 40 TC 3 Z9 3 U1 1 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD MAR 30 PY 2011 VL 412 IS 1 BP 46 EP 54 DI 10.1016/j.virol.2011.01.001 PG 9 WC Virology SC Virology GA 740FY UT WOS:000288778200006 PM 21256532 ER PT J AU Woodson, SE Freiberg, AN Holbrook, MR AF Woodson, Sara E. Freiberg, Alexander N. Holbrook, Michael R. TI Differential cytokine responses from primary human Kupffer cells following infection with wild-type or vaccine strain yellow fever virus SO VIROLOGY LA English DT Article DE Kupffer cell; Yellow fever virus; IL-8; IL-10; RANTES/CCL5; TNF-alpha ID TUMOR-NECROSIS-FACTOR; GENE-EXPRESSION; VISCEROTROPIC DISEASE; IMMUNE-RESPONSE; LIVER-INJURY; INFLAMMATION; HISTOPATHOLOGY; REGENERATION; ACTIVATION; ALPHA AB Wild-type yellow fever virus (YFV) infections result in a hepatotropic disease which is often fatal, while vaccination with the live-attenuated 17-D strain results in productive infection yet is well-tolerated with few adverse events. Kupffer cells (KCs) are resident liver macrophages that have a significant role in pathogen detection, clearance and immune signaling. Although KCs appear to be an important component of YF disease, their role has been under-studied. This study examined cytokine responses in KCs following infection with either wild-type or vaccine strains of YFV. Results indicate that KCs support replication of wild-type and vaccine strains, yet wild-type YFV induced a prominent and prolonged pro-inflammatory cytokine response (IL-8, TNF-alpha and RANTES/CCL5) with little control by a major anti-inflammatory cytokine (IL-10). This response was significantly reduced in vaccine strain infections. These data suggest that a differentially regulated infection in KCs may play a critical role in development of disease. (c) 2011 Elsevier Inc. All rights reserved. C1 [Holbrook, Michael R.] NIAID Integrated Res Facil, Frederick, MD 21702 USA. [Woodson, Sara E.; Freiberg, Alexander N.; Holbrook, Michael R.] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77550 USA. [Woodson, Sara E.; Freiberg, Alexander N.; Holbrook, Michael R.] Univ Texas Med Branch, Inst Human Infect & Immun, Galveston, TX 77550 USA. RP Holbrook, MR (reprint author), NIAID Integrated Res Facil, 8200 Res Plaza, Frederick, MD 21702 USA. EM Michael.holbrook@nih.gov NR 30 TC 8 Z9 8 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 0042-6822 J9 VIROLOGY JI Virology PD MAR 30 PY 2011 VL 412 IS 1 BP 188 EP 195 DI 10.1016/j.virol.2011.01.012 PG 8 WC Virology SC Virology GA 740FY UT WOS:000288778200021 PM 21277609 ER PT J AU Gezmu, M DeGruttola, V Dixon, D Essex, M Halloran, E Hogan, J Grobler, A Kim, S McDermott, J McKaiga, R Neatonh, JD AF Gezmu, Misrak DeGruttola, Victor Dixon, Dennis Essex, Max Halloran, Elizabeth Hogan, Joseph Grobler, Anneke Kim, Soyeon McDermott, Jeanne McKaiga, Rosemary Neatonh, James D. TI Strengthening biostatistics resources in sub-Saharan Africa: Research collaborations through U.S. partnerships SO STATISTICS IN MEDICINE LA English DT Article DE biostatistics; sub-Saharan Africa; collaboration; capacity building; global health; training program ID US AB On September 30, 2009, the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) conducted a workshop on strengthening biostatistics resources in sub-Saharan Africa (SSA). An increase in global spending on health research over the last decade has boosted funds available to conduct biomedical research in low-to mid-income countries. The HIV/AIDS pandemic, the re-emergence of malaria and tuberculosis, and other emerging infectious agents are major driving forces behind the increase in biomedical research and clinical care programs (clinical trials, observational studies and, other public health programs) in SSA (Exp. Biol. Med. 2008; 233: 277-285). In addition, the increased engagement of the United States (U. S.) government through the Global Health Initiative, which expands the traditional focus beyond infectious diseases to other causes of poor health and to the recognition of need the to strengthen health systems for a sustainable response, only increases the need for in-depth in-country expertise in all aspects of biomedical research (White House Press Release, 2009). In this workshop, researchers both from the U. S. and SSA were invited to discuss their collaborative work, to discuss ways in which biostatistical activities are carried out within their research projects, and to identify both general and specific needs for capacity building in biostatistics. Capacity building discussions highlighted the critical need to increase the number of well-trained in-country biostatisticians, both to participate in ongoing studies and to contribute to an infrastructure that can produce the next generation of biostatistical researchers. Copyright (C) 2011 John Wiley & Sons, Ltd. C1 [Gezmu, Misrak; McKaiga, Rosemary] NIAID, NIH, Bethesda, MD 20892 USA. [DeGruttola, Victor; Dixon, Dennis] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Halloran, Elizabeth] Univ Washington, Seattle, WA 98195 USA. [Halloran, Elizabeth] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Hogan, Joseph] Brown Univ, Ctr Stat Sci, Providence, RI 02912 USA. [Grobler, Anneke] Univ KwaZulu Natal, Ctr AIDS Programme Res S Africa, Durban, South Africa. [Kim, Soyeon] Univ Med & Dent New Jersey, Newark, NJ 07103 USA. [McDermott, Jeanne] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Neatonh, James D.] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. RP Gezmu, M (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM mgezmu@niaid.nih.gov RI Hogan, Joseph/J-4579-2014; OI Hogan, Joseph/0000-0001-7959-7361 FU Intramural NIH HHS [Z99 AI999999]; NIAID NIH HHS [P30 AI042853] NR 11 TC 11 Z9 11 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAR 30 PY 2011 VL 30 IS 7 BP 695 EP 708 DI 10.1002/sim.4144 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 736RV UT WOS:000288512700001 PM 21394746 ER PT J AU Turkbey, B Xu, S Kruecker, J Locklin, J Pang, YX Shah, V Bernardo, M Baccala, A Rastinehad, A Benjamin, C Merino, MJ Wood, BJ Choyke, PL Pinto, PA AF Turkbey, Baris Xu, Sheng Kruecker, Jochen Locklin, Julia Pang, Yuxi Shah, Vijay Bernardo, Marcelino Baccala, Angelo Rastinehad, Ardeshir Benjamin, Compton Merino, Maria J. Wood, Bradford J. Choyke, Peter L. Pinto, Peter A. TI Documenting the location of systematic transrectal ultrasound-guided prostate biopsies: correlation with multi-parametric MRI SO CANCER IMAGING LA English DT Article DE Prostate cancer; multi-parametric MR imaging; TRUS/MRI fusion tracking ID MAPPING BIOPSY; CANCER; FUSION AB During transrectal ultrasound (TRUS)-guided prostate biopsies, the actual location of the biopsy site is rarely documented. Here, we demonstrate the capability of TRUS-magnetic resonance imaging (MRI) image fusion to document the biopsy site and correlate biopsy results with multi-parametric MRI findings. Fifty consecutive patients (median age 61 years) with a median prostate-specific antigen (PSA) level of 5.8 ng/ml underwent 12-core TRUS-guided biopsy of the prostate. Pre-procedural T2-weighted magnetic resonance images were fused to TRUS. A disposable needle guide with miniature tracking sensors was attached to the TRUS probe to enable fusion with MRI. Real-time TRUS images during biopsy and the corresponding tracking information were recorded. Each biopsy site was superimposed onto the MRI. Each biopsy site was classified as positive or negative for cancer based on the results of each MRI sequence. Sensitivity, specificity, and receiver operating curve (ROC) area under the curve (AUC) values were calculated for multi-parametric MRI. Gleason scores for each multi-parametric MRI pattern were also evaluated. Six hundred and 5 systemic biopsy cores were analyzed in 50 patients, of whom 20 patients had 56 positive cores. MRI identified 34 of 56 positive cores. Overall, sensitivity, specificity, and ROC area values for multi-parametric MRI were 0.607, 0.727, 0.667, respectively. TRUS-MRI fusion after biopsy can be used to document the location of each biopsy site, which can then be correlated with MRI findings. Based on correlation with tracked biopsies, T2-weighted MRI and apparent diffusion coefficient maps derived from diffusion-weighted MRI are the most sensitive sequences, whereas the addition of delayed contrast enhancement MRI and three-dimensional magnetic resonance spectroscopy demonstrated higher specificity consistent with results obtained using radical prostatectomy specimens. C1 [Shah, Vijay; Bernardo, Marcelino; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. [Xu, Sheng; Kruecker, Jochen] Philips Res N Amer, Briarcliff Manor, NY USA. [Locklin, Julia; Wood, Bradford J.] NCI, Ctr Intervent Oncol, Bethesda, MD 20892 USA. [Locklin, Julia; Wood, Bradford J.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Pang, Yuxi] Philips Healthcare, Cleveland, OH USA. [Shah, Vijay; Bernardo, Marcelino] NCI Frederick, SAIC Frederick, Frederick, MD USA. [Baccala, Angelo; Rastinehad, Ardeshir; Benjamin, Compton; Pinto, Peter A.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. [Merino, Maria J.] NCI, Lab Pathol, NIH, Bethesda, MD 20892 USA. RP Choyke, PL (reprint author), NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. EM pchoyke@mail.nih.gov RI Shah, Vijay/D-4083-2014 OI Shah, Vijay/0000-0003-3856-156X FU NIH; NCI [HHSN261200800001E] FX NIH and Philips have intellectual property in the field. This study was supported in part by the Intramural Research Program of the NIH. NCI contract number HHSN261200800001E. NR 9 TC 10 Z9 11 U1 0 U2 1 PU E-MED PI LONDON PA PO BOX 29761, LONDON, NW3 7ZS, ENGLAND SN 1470-7330 J9 CANCER IMAGING JI Cancer Imaging PD MAR 29 PY 2011 VL 11 IS 1 BP 31 EP 36 DI 10.1102/1470-7330.2011.0007 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 826CY UT WOS:000295330200001 PM 21450548 ER PT J AU Suh, YH Yoshimoto-Furusawa, A Weih, KA Tessarollo, L Roche, KW Mackem, S Roche, PA AF Suh, Young Ho Yoshimoto-Furusawa, Aki Weih, Karis A. Tessarollo, Lino Roche, Katherine W. Mackem, Susan Roche, Paul A. TI Deletion of SNAP-23 Results in Pre-Implantation Embryonic Lethality in Mice SO PLOS ONE LA English DT Article ID PANCREATIC ACINAR-CELLS; REGULATED EXOCYTOSIS; KNOCKOUT MICE; MAST-CELLS; STEM-CELLS; SNARE; TRAFFICKING; SURFACE; MECHANISMS; SYNTAXIN AB SNARE-mediated membrane fusion is a pivotal event for a wide-variety of biological processes. SNAP-25, a neuron-specific SNARE protein, has been well-characterized and mouse embryos lacking Snap25 are viable. However, the phenotype of mice lacking SNAP-23, the ubiquitously expressed SNAP-25 homolog, remains unknown. To reveal the importance of SNAP-23 function in mouse development, we generated Snap23-null mice by homologous recombination. We were unable to obtain newborn SNAP-23-deficient mice, and analysis of pre-implantation embryos from Snap23(Delta/wt) matings revealed that Snap23-null blastocysts were dying prior to implantation at embryonic day E3.5. Thus these data reveal a critical role for SNAP-23 during embryogenesis. C1 [Suh, Young Ho; Weih, Karis A.; Roche, Paul A.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. [Suh, Young Ho; Roche, Katherine W.] NINDS, Receptor Biol Sect, NIH, Bethesda, MD 20892 USA. [Suh, Young Ho] Ajou Univ, Sch Med, Dept Pharmacol, Grad Program Neurosci, Suwon 441749, South Korea. [Tessarollo, Lino] NCI, Mouse Canc Genet Program, CCR, NIH, Frederick, MD 21701 USA. [Yoshimoto-Furusawa, Aki; Mackem, Susan] NCI, Canc & Dev Biol Lab, CCR, NIH, Frederick, MD 21701 USA. RP Suh, YH (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM paul.roche@nih.gov OI Roche, Katherine/0000-0001-7282-6539 FU NCI; NINDS; Integrative Neural Immune Program FX This research was supported by the NCI Intramural Research Program (Y.H.S., A.Y.-F., L.T, S.M. and P.A.R.), the NINDS Intramural Research Program (Y.H.S., and K.W.R.), and the Integrative Neural Immune Program (Y.H.S. fellowship). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 32 TC 10 Z9 10 U1 1 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 29 PY 2011 VL 6 IS 3 AR e18444 DI 10.1371/journal.pone.0018444 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 743YC UT WOS:000289054600052 PM 21479242 ER PT J AU Mancini, C Kenchaiah, S Bodurian, E Arai, AE Bandettini, WP AF Mancini, Christine Kenchaiah, Satish Bodurian, Edward Arai, Andrew E. Bandettini, W. Patricia TI Embolization of an Intracardiac Thrombus During a Cardiovascular Magnetic Resonance Imaging Study SO CIRCULATION LA English DT Editorial Material ID TRANSESOPHAGEAL ECHOCARDIOGRAPHY; ATRIAL-FIBRILLATION; CARDIOVERSION C1 [Mancini, Christine; Kenchaiah, Satish; Arai, Andrew E.; Bandettini, W. Patricia] Natl Inst Hlth, Dept Hlth & Human Serv, Natl Heart Lung & Blood Inst, Bethesda, MD 20892 USA. [Bodurian, Edward] Suburban Hosp Johns Hopkins Med, Bethesda, MD USA. RP Bandettini, WP (reprint author), Natl Inst Hlth, Dept Hlth & Human Serv, Natl Heart Lung & Blood Inst, 10 Ctr Dr,Bldg 10,Rm B1D-416, Bethesda, MD 20892 USA. EM ingkanisorn@nih.gov RI Kenchaiah, Satish/A-1519-2016 FU Intramural NIH HHS [ZID HL006140-02, ZIA HL004607-12] NR 4 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 29 PY 2011 VL 123 IS 12 BP E388 EP E389 DI 10.1161/CIRCULATIONAHA.110.983916 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 741UU UT WOS:000288891700003 PM 21444890 ER PT J AU McGlinchey, RP Kryndushkin, D Wickner, RB AF McGlinchey, Ryan P. Kryndushkin, Dmitry Wickner, Reed B. TI Suicidal [PSI+] is a lethal yeast prion SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SACCHAROMYCES-CEREVISIAE; MESSENGER-RNA; SUP35 PROTEIN; IN-VITRO; URE3; DOMAIN; GENE; INCOMPATIBILITY; TRANSMISSION; SUPPRESSOR AB [PSI+] is a prion of the essential translation termination factor Sup35p. Although mammalian prion infections are uniformly fatal, commonly studied [PSI+] variants do not impair growth, leading to suggestions that [PSI+] may protect against stress conditions. We report here that over half of [PSI+] variants are sick or lethal. These "killer [PSI+]s" are compatible with cell growth only when also expressing minimal Sup35C, lacking the N-terminal prion domain. The severe detriment of killer [PSI+] results in rapid selection of nonkiller [PSI+] variants or loss of the prion. We also report variants of [URE3], a prion of the nitrogen regulation protein Ure2p, that grow much slower than ure2 Delta cells. Our findings give a more realistic picture of the impact of the prion change than does focus on "mild" prion variants. C1 [McGlinchey, Ryan P.; Kryndushkin, Dmitry; Wickner, Reed B.] NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Wickner, RB (reprint author), NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. EM wickner@helix.nih.gov FU National Institute of Diabetes Digestive and Kidney Diseases FX We thank Herman Edskes for pH952, our colleagues for critical reading of the manuscript, and Frank Shewmaker for fruitful discussions. This work was supported by the Intramural Program of the National Institute of Diabetes Digestive and Kidney Diseases. NR 41 TC 85 Z9 85 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 29 PY 2011 VL 108 IS 13 BP 5337 EP 5341 DI 10.1073/pnas.1102762108 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 741VY UT WOS:000288894800041 PM 21402947 ER PT J AU Sandovici, I Smith, NH Nitert, MD Ackers-Johnson, M Uribe-Lewis, S Ito, Y Jones, RH Marquez, VE Cairns, W Tadayyon, M O'Neill, LP Murrell, A Ling, C Constancia, M Ozanne, SE AF Sandovici, Ionel Smith, Noel H. Nitert, Marloes Dekker Ackers-Johnson, Matthew Uribe-Lewis, Santiago Ito, Yoko Jones, R. Huw Marquez, Victor E. Cairns, William Tadayyon, Mohammed O'Neill, Laura P. Murrell, Adele Ling, Charlotte Constancia, Miguel Ozanne, Susan E. TI Maternal diet and aging alter the epigenetic control of a promoter-enhancer interaction at the Hnf4a gene in rat pancreatic islets SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE maternal nutrition; developmental programming; DNA methylation; histone modifications; diet-gene interactions ID TRANSCRIPTION FACTORS; DEVELOPMENTAL ORIGINS; ENDOCRINE PANCREAS; EXPRESSION; HNF-4-ALPHA; DISEASE; SUSCEPTIBILITY; METHYLATION; DISRUPTION; UPSTREAM AB Environmental factors interact with the genome throughout life to determine gene expression and, consequently, tissue function and disease risk. One such factor that is known to play an important role in determining long-term metabolic health is diet during critical periods of development. Epigenetic regulation of gene expression has been implicated in mediating these programming effects of early diet. The precise epigenetic mechanisms that underlie these effects remain largely unknown. Here, we show that the transcription factor Hnf4a, which has been implicated in the etiology of type 2 diabetes (T2D), is epigenetically regulated by maternal diet and aging in rat islets. Transcriptional activity of Hnf4a in islets is restricted to the distal P2 promoter through its open chromatin configuration and an islet-specific interaction between the P2 promoter and a downstream enhancer. Exposure to suboptimal nutrition during early development leads to epigenetic silencing at the enhancer region, which weakens the P2 promoter-enhancer interaction and results in a permanent reduction in Hnf4a expression. Aging leads to progressive epigenetic silencing of the entire Hnf4a locus in islets, an effect that is more pronounced in rats exposed to a poor maternal diet. Our findings provide evidence for environmentally induced epigenetic changes at the Hnf4a enhancer that alter its interaction with the P2 promoter, and consequently determine T2D risk. We therefore propose that environmentally induced changes in promoter-enhancer interactions represent a fundamental epigenetic mechanism by which nutrition and aging can influence long-term health. C1 [Sandovici, Ionel; Constancia, Miguel] Univ Cambridge, Dept Obstet & Gynaecol, Metab Res Labs, Cambridge CB2 0SW, England. [Sandovici, Ionel; Constancia, Miguel] Univ Cambridge, Ctr Trophoblast Res, Cambridge CB2 3EG, England. [Smith, Noel H.; Ackers-Johnson, Matthew; Jones, R. Huw; Ozanne, Susan E.] Univ Cambridge, Inst Metab Sci, Metab Res Labs, Cambridge CB2 OQQ, England. [Nitert, Marloes Dekker; Ling, Charlotte] Lund Univ, Malmo Univ Hosp, Diabet & Endocrinol Res Unit, S-20502 Malmo, Sweden. [Uribe-Lewis, Santiago; Ito, Yoko; Murrell, Adele] Univ Cambridge, Dept Oncol, Canc Res United Kingdom Cambridge Res Inst, Cambridge CB2 0RE, England. [Marquez, Victor E.] NCI, Biol Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. [Cairns, William; Tadayyon, Mohammed] GlaxoSmithKline Inc, Med Res Ctr, Biol Reagents & Assay Dev, Stevenage SG1 2NY, Herts, England. [O'Neill, Laura P.] Univ Birmingham, Sch Med, Inst Biomed Res, Chromatin & Gene Express Grp, Birmingham B15 2TT, W Midlands, England. RP Constancia, M (reprint author), Univ Cambridge, Dept Obstet & Gynaecol, Metab Res Labs, Cambridge CB2 0SW, England. EM jmasmc2@cam.ac.uk; seo10@cam.ac.uk RI Constancia, Miguel/F-6654-2013; Dekker Nitert, Marloes/A-8822-2011; Ling, Charlotte/Q-2432-2015 OI Dekker Nitert, Marloes/0000-0002-1909-8920; Ling, Charlotte/0000-0003-0587-7154 FU Biotechnology and Biological Sciences Research Council; British Heart Foundation; FP6 Epigenome Network of Excellence programme; GlaxoSmithKline; Nuffield Foundation; Royal Society; National Institute for Health Research Cambridge Biomedical Research Centre; Medical Research Council Centre for Obesity and Related Metabolic Diseases; Swedish Research Council; Region Skane; Novo Nordisk; Soderberg; Pahlsson; Linne [B31 5631/2006]; Wellcome Trust FX We thank N. Wakes, S. Dowd, U. Obi, A. Wayman, and D. Hawkes for technical assistance; F. Reimann for providing INS-1 cells; M. Rehli for supplying the pCpGL vector; and D. Schmidt and D. Odom for access to unpublished data. This work was supported by the Biotechnology and Biological Sciences Research Council, the British Heart Foundation, the FP6 Epigenome Network of Excellence programme, GlaxoSmithKline, the Nuffield Foundation, the Royal Society, the National Institute for Health Research Cambridge Biomedical Research Centre, and the Medical Research Council Centre for Obesity and Related Metabolic Diseases. Studies in Malmo were funded by grants from the Swedish Research Council, Region Skane, Novo Nordisk, Soderberg, Pahlsson, and Linne (Grant B31 5631/2006). S.E.O. is a British Heart Foundation Senior Fellow. M.A.-J. is supported by a scholarship from the Wellcome Trust. NR 35 TC 147 Z9 154 U1 1 U2 22 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 MAR 29 PY 2011 VL 108 IS 13 BP 5449 EP 5454 DI 10.1073/pnas.1019007108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 741VY UT WOS:000288894800060 PM 21385945 ER PT J AU Yap, TL Pfefferkorn, CM Lee, JC AF Yap, Thai Leong Pfefferkorn, Candace M. Lee, Jennifer C. TI Residue-Specific Fluorescent Probes of alpha-Synuclein: Detection of Early Events at the N- and C-Termini during Fibril Assembly SO BIOCHEMISTRY LA English DT Article ID SOLID-STATE NMR; PARKINSONS-DISEASE; AMYLOID FIBRILS; TRYPTOPHAN FLUORESCENCE; PROTEIN AGGREGATION; MECHANISM; INSIGHTS; CONSEQUENCES; SPECTROSCOPY; OLIGOMERS AB In the Parkinson's disease-associated state, a-synuclein undergoes large conformational changes, forming ordered, beta-sheet-containing fibrils. To unravel the role of specific residues during the fibril assembly process, we prepared single-Cys mutants in the disordered (G7C and Y136C) and proximal (V26C and L100C) fibril core sites and derivatized them with environmentally sensitive dansyl (Dns) fluorophores. Dns fluorescence exhibits residue specificity in spectroscopic properties as well as kinetic behavior; early kinetic events were revealed by probes located at positions 7 and 136 compared to those at positions 26 and 100. C1 [Yap, Thai Leong; Pfefferkorn, Candace M.; Lee, Jennifer C.] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Lee, JC (reprint author), NHLBI, Lab Mol Biophys, NIH, 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 Heart, Lung, and Blood Institute, National Institutes of Health FX Supported by the Intramural Research Program of the National Heart, Lung, and Blood Institute, National Institutes of Health. NR 36 TC 15 Z9 15 U1 1 U2 16 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 29 PY 2011 VL 50 IS 12 BP 1963 EP 1965 DI 10.1021/bi2000824 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 737MS UT WOS:000288573500001 PM 21338068 ER PT J AU Cloe, AL Orgel, JPRO Sachleben, JR Tycko, R Meredith, SC AF Cloe, Adam L. Orgel, Joseph P. R. O. Sachleben, Joseph R. Tycko, Robert Meredith, Stephen C. TI The Japanese Mutant A beta (Delta E22-A beta(1-39)) Forms Fibrils Instantaneously, with Low-Thioflavin T Fluorescence: Seeding of Wild-Type A beta(1-40) into Atypical Fibrils by Delta E22-A beta(1-39) SO BIOCHEMISTRY LA English DT Article ID HEREDITARY CEREBRAL-HEMORRHAGE; SOLID-STATE NMR; AMYLOID FIBRILS; ALZHEIMERS-DISEASE; EXPERIMENTAL CONSTRAINTS; MOLECULAR-MECHANISM; SYNAPTIC ALTERATION; STRUCTURAL BASIS; PROTEIN; AGGREGATION AB The Delta E693 (Japanese) mutation of the beta-amyloid precursor protein leads to production of Delta E22-A beta peptides such as Delta E22-A beta(1-39). Despite reports that these peptides do not form fibrils, here we show that, on the contrary, the peptide forms fibrils essentially instantaneously. The fibrils are typical amyloid fibrils in all respects except that they cause only low levels of thioflavin T (ThT) fluorescence, which, however, develops with no lag phase. The fibrils bind ThT, but with a lower affinity and a smaller number of binding sites than wild-type (WT) A beta(1-40). Fluorescence depolarization confirms extremely rapid aggregation of Delta E22-A beta(1-39). Size exclusion chromatography (SEC) indicates very low concentrations of soluble monomer and oligomer, but only in the presence of some organic solvent, e.g., 2% (v/v) DMSO. The critical concentration is approximately 1 order of magnitude lower for Delta E22-A beta(1-39) than for WT A beta(1-40). Several lines of evidence point to an altered structure for Delta E22-A beta(1-39) compared to that of WT A beta(1-40) fibrils. In addition to differences in ThT binding and fluorescence, PITHIRDS-CT solid-state nuclear magnetic resonance (NMR) measurements of Delta E22-A beta(1-39) are not compatible with the parallel in-register beta-sheet generally observed for WT A beta(1-40) fibrils. X-ray fibril diffraction showed different D spacings: 4.7 and 10.4 A for WT A beta(1-40) and 4.7 and 9.6 angstrom for Delta E22-A beta(1-39). Equimolar mixtures of Delta E22-A beta(1-39) and WT A beta(1-40) also produced fibrils extremely rapidly, and by the criteria of ThT fluorescence and electron microscopic appearance, they were the same as fibrils made from pure Delta E22-A beta(1-39). X-ray diffraction of fibrils formed from 1:1 molar mixtures of Delta E22-A beta(1-39) and WT A beta(1-40) showed the same D spacings as fibrils of the pure mutant peptide, not the wild-type peptide. These findings are consistent with extremely rapid nucleation by Delta E22-A beta(1-39), followed by fibril extension by WT A beta(1-40), and "conversion" of the wild type peptide to a structure similar to that of the mutant peptide, in a manner reminiscent of the prion conversion phenomenon. C1 [Cloe, Adam L.; Meredith, Stephen C.] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. [Orgel, Joseph P. R. O.] IIT, Pritzker Inst Biomed Sci & Engn, BioCAT & uCoSM, Chicago, IL 60616 USA. [Orgel, Joseph P. R. O.] IIT, CSRRI, Chicago, IL 60616 USA. [Orgel, Joseph P. R. O.] IIT, Dept Biol Chem & Phys Sci, Chicago, IL 60616 USA. [Tycko, Robert] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. [Meredith, Stephen C.] Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA. [Tycko, Robert] Univ Chicago, Shared Res Facil, Biomol NMR Facil, Chicago, IL 60637 USA. RP Meredith, SC (reprint author), Univ Chicago, Dept Pathol, 5841 S Maryland Ave, Chicago, IL 60637 USA. EM scmeredi@uchicago.edu RI ID, BioCAT/D-2459-2012 FU National Institutes of Health (NIH) [NS042852]; Alzheimer's Association [IIRG-06-27794]; National Science Foundation [MCB-0644015]; National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health; U.S. Department of Energy, Basic Energy Sciences, Office of Science [W-31-109-ENG-38]; National Institutes of Health-supported Research Center [Grant RR-08630] FX We acknowledge support from the National Institutes of Health (NIH) (Grant NS042852 to S.C.M.), the Alzheimer's Association (Grant IIRG-06-27794 to S.C.M.), and the National Science Foundation (MCB-0644015 CAREER, J.P.R.O.O.). This work was supported in part by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. Use of the Advanced Photon Source was supported by the U.S. Department of Energy, Basic Energy Sciences, Office of Science, under Contract W-31-109-ENG-38. BioCAT is a National Institutes of Health-supported Research Center (Grant RR-08630). NR 49 TC 44 Z9 45 U1 1 U2 33 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 29 PY 2011 VL 50 IS 12 BP 2026 EP 2039 DI 10.1021/bi1016217 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 737MS UT WOS:000288573500007 PM 21291268 ER PT J AU Laayouni, H Montanucci, L Sikora, M Mele, M Dall'Olio, GM Lorente-Galdos, B McGee, KM Graffelman, J Awadalla, P Bosch, E Comas, D Navarro, A Calafell, F Casals, F Bertranpetit, J AF Laayouni, Hafid Montanucci, Ludovica Sikora, Martin Mele, Marta Marco Dall'Olio, Giovanni Lorente-Galdos, Belen McGee, Kate M. Graffelman, Jan Awadalla, Philip Bosch, Elena Comas, David Navarro, Arcadi Calafell, Francesc Casals, Ferran Bertranpetit, Jaume TI Similarity in Recombination Rate Estimates Highly Correlates with Genetic Differentiation in Humans SO PLOS ONE LA English DT Article ID CELL-LINE PANEL; HUMAN GENOME; HUMAN-POPULATIONS; LINKAGE DISEQUILIBRIUM; MEIOTIC RECOMBINATION; HAPLOTYPE MAP; PATTERNS; HOTSPOTS; ASSOCIATION; CHIMPANZEES AB Recombination varies greatly among species, as illustrated by the poor conservation of the recombination landscape between humans and chimpanzees. Thus, shorter evolutionary time frames are needed to understand the evolution of recombination. Here, we analyze its recent evolution in humans. We calculated the recombination rates between adjacent pairs of 636,933 common single-nucleotide polymorphism loci in 28 worldwide human populations and analyzed them in relation to genetic distances between populations. We found a strong and highly significant correlation between similarity in the recombination rates corrected for effective population size and genetic differentiation between populations. This correlation is observed at the genome-wide level, but also for each chromosome and when genetic distances and recombination similarities are calculated independently from different parts of the genome. Moreover, and more relevant, this relationship is robustly maintained when considering presence/absence of recombination hotspots. Simulations show that this correlation cannot be explained by biases in the inference of recombination rates caused by haplotype sharing among similar populations. This result indicates a rapid pace of evolution of recombination, within the time span of differentiation of modern humans. C1 [Laayouni, Hafid; Montanucci, Ludovica; Sikora, Martin; Mele, Marta; Marco Dall'Olio, Giovanni; Lorente-Galdos, Belen; Bosch, Elena; Comas, David; Navarro, Arcadi; Calafell, Francesc; Casals, Ferran; Bertranpetit, Jaume] CEXS UPF PRBB, Inst Evolutionary Biol UPF CSIC, IBE, Barcelona, Catalonia, Spain. [McGee, Kate M.] NCI, NIH, Frederick, MD 21701 USA. [Graffelman, Jan] Univ Politecn Cataluna, Dept Stat & Operat Res, Barcelona, Spain. [Awadalla, Philip; Casals, Ferran] Univ Montreal, Fac Med, Ste Justine Hosp, Res Ctr, Montreal, PQ H3C 3J7, Canada. [Navarro, Arcadi] Inst Catalana Recerca & Estudis Avancats, Barcelona, Catalonia, Spain. [Navarro, Arcadi] Natl Inst Bioinformat INB, Barcelona, Spain. RP Laayouni, H (reprint author), CEXS UPF PRBB, Inst Evolutionary Biol UPF CSIC, IBE, Barcelona, Catalonia, Spain. EM jaume.bertranpetit@upf.edu RI Bertranpetit, Jaume/F-8550-2012; Calafell, Francesc/C-8595-2014; Comas, David/D-5382-2014; Bosch, Elena/D-8681-2014; Navarro, Arcadi/F-1592-2011; Sikora, Martin/C-8609-2015; Graffelman, Jan/L-8056-2014; Casals, Ferran/H-4347-2015; OI Bertranpetit, Jaume/0000-0003-0100-0590; Calafell, Francesc/0000-0002-1083-9438; Comas, David/0000-0002-5075-0956; Bosch, Elena/0000-0003-2848-103X; Navarro, Arcadi/0000-0003-2162-8246; Sikora, Martin/0000-0003-2818-8319; Graffelman, Jan/0000-0003-3900-0780; Casals, Ferran/0000-0002-8941-0369; Dall'Olio, Giovanni Marco/0000-0001-9057-2480; Lorente-Galdos, Belen/0000-0001-5390-2452; Laayouni, Hafid/0000-0003-1297-5078 FU Ministerio de Educacion y Ciencia (Spain) [BFU2007-63657, BFU2009-13409-C02-02, SAF-2007-63171]; Direccio General de Recerca of Generalitat de Catalunya (Grup de Recerca Consolidat) [2005SGR/00608, 2009 SGR 1101]; National Institute for Bioinformatics FX This research was funded by grants BFU2007-63657, BFU2009-13409-C02-02 and SAF-2007-63171 awarded by Ministerio de Educacion y Ciencia (Spain), by the Direccio General de Recerca of Generalitat de Catalunya (Grup de Recerca Consolidat 2005SGR/00608 and 2009 SGR 1101), and by the National Institute for Bioinformatics (www.inab.org), a platform of Genoma Espana. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 37 TC 6 Z9 7 U1 1 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 28 PY 2011 VL 6 IS 3 AR e17913 DI 10.1371/journal.pone.0017913 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 743XV UT WOS:000289053800005 PM 21464928 ER PT J AU Liu, XH Xu, WQ Russ, J Eiden, LE Eiden, MV AF Liu, Xiu-Huai Xu, Wenqin Russ, Jill Eiden, Lee E. Eiden, Maribeth V. TI The Host Range of Gammaretroviruses and Gammaretroviral Vectors Includes Post-Mitotic Neural Cells SO PLOS ONE LA English DT Article ID NERVE GROWTH-FACTOR; IMMUNODEFICIENCY-VIRUS TYPE-1; MURINE LEUKEMIA-VIRUS; CEREBRAL CORTICAL-NEURONS; PC12 CELLS; NUCLEAR IMPORT; PREINTEGRATION COMPLEX; FLUORESCENT PROTEIN; GENE-THERAPY; RETROVIRUS AB Background: Gammaretroviruses and gammaretroviral vectors, in contrast to lentiviruses and lentiviral vectors, are reported to be restricted in their ability to infect growth-arrested cells. The block to this restriction has never been clearly defined. The original assessment of the inability of gammaretroviruses and gammaretroviral vectors to infect growth-arrested cells was carried out using established cell lines that had been growth-arrested by chemical means, and has been generalized to neurons, which are post-mitotic. We re-examined the capability of gammaretroviruses and their derived vectors to efficiently infect terminally differentiated neuroendocrine cells and primary cortical neurons, a target of both experimental and therapeutic interest. Methodology/Principal Findings: Using GFP expression as a marker for infection, we determined that both growth-arrested (NGF-differentiated) rat pheochromocytoma cells (PC12 cells) and primary rat cortical neurons could be efficiently transduced, and maintained long-term protein expression, after exposure to murine leukemia virus (MLV) and MLV-based retroviral vectors. Terminally differentiated PC12 cells transduced with a gammaretroviral vector encoding the antiapoptotic protein Bcl-xL were protected from cell death induced by withdrawal of nerve growth factor (NGF), demonstrating gammaretroviral vector-mediated delivery and expression of genes at levels sufficient for therapeutic effect in non-dividing cells. Post-mitotic rat cortical neurons were also shown to be susceptible to transduction by murine replication-competent gammaretroviruses and gammaretroviral vectors. Conclusions/Significance: These findings suggest that the host range of gammaretroviruses includes post-mitotic and other growth-arrested cells in mammals, and have implications for re-direction of gammaretroviral gene therapy to neurological disease. C1 [Liu, Xiu-Huai; Eiden, Lee E.] NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. [Xu, Wenqin; Russ, Jill; Eiden, Maribeth V.] NIMH, Sect Directed Gene Transfer, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. RP Liu, XH (reprint author), NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. EM eidenm@mail.nih.gov OI Eiden, Lee/0000-0001-7524-944X FU National Institute of Mental Health FX This work was funded by the National Institute of Mental Health Intramural Research Program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 52 TC 4 Z9 4 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 28 PY 2011 VL 6 IS 3 AR e18072 DI 10.1371/journal.pone.0018072 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 743XV UT WOS:000289053800021 PM 21464894 ER PT J AU Shrestha, B Reed, JM Starks, PT Kaufman, GE Goldstone, JV Roelke, ME O'Brien, SJ Koepfli, KP Frank, LG Court, MH AF Shrestha, Binu Reed, J. Michael Starks, Philip T. Kaufman, Gretchen E. Goldstone, Jared V. Roelke, Melody E. O'Brien, Stephen J. Koepfli, Klaus-Peter Frank, Laurence G. Court, Michael H. TI Evolution of a Major Drug Metabolizing Enzyme Defect in the Domestic Cat and Other Felidae: Phylogenetic Timing and the Role of Hypercarnivory SO PLOS ONE LA English DT Article ID DEFICIENT ACETAMINOPHEN GLUCURONIDATION; SPECIES-DIFFERENCES; CONJUGATION; BIOTRANSFORMATION; SUPERFAMILY; PSEUDOGENES; CARNIVORA; ELEPHANT; GENOME; UGT1A6 AB The domestic cat (Felis catus) shows remarkable sensitivity to the adverse effects of phenolic drugs, including acetaminophen and aspirin, as well as structurally-related toxicants found in the diet and environment. This idiosyncrasy results from pseudogenization of the gene encoding UDP-glucuronosyltransferase (UGT) 1A6, the major species-conserved phenol detoxification enzyme. Here, we established the phylogenetic timing of disruptive UGT1A6 mutations and explored the hypothesis that gene inactivation in cats was enabled by minimal exposure to plant-derived toxicants. Fixation of the UGT1A6 pseudogene was estimated to have occurred between 35 and 11 million years ago with all extant Felidae having dysfunctional UGT1A6. Out of 22 additional taxa sampled, representative of most Carnivora families, only brown hyena (Parahyaena brunnea) and northern elephant seal (Mirounga angustirostris) showed inactivating UGT1A6 mutations. A comprehensive literature review of the natural diet of the sampled taxa indicated that all species with defective UGT1A6 were hypercarnivores (>70% dietary animal matter). Furthermore those species with UGT1A6 defects showed evidence for reduced amino acid constraint (increased dN/dS ratios approaching the neutral selection value of 1.0) as compared with species with intact UGT1A6. In contrast, there was no evidence for reduced amino acid constraint for these same species within UGT1A1, the gene encoding the enzyme responsible for detoxification of endogenously generated bilirubin. Our results provide the first evidence suggesting that diet may have played a permissive role in the devolution of a mammalian drug metabolizing enzyme. Further work is needed to establish whether these preliminary findings can be generalized to all Carnivora. C1 [Shrestha, Binu; Court, Michael H.] Tufts Univ, Sch Med, Dept Mol Physiol & Pharmacol, Comparat & Mol Pharmacogen Lab, Boston, MA 02111 USA. [Shrestha, Binu; Reed, J. Michael; Starks, Philip T.] Tufts Univ, Dept Biol, Medford, MA 02155 USA. [Kaufman, Gretchen E.] Tufts Cummings Sch Vet Med, Dept Environm & Populat Hlth, North Grafton, MA USA. [Goldstone, Jared V.] Woods Hole Oceanog Inst, Dept Biol, Woods Hole, MA 02543 USA. [Roelke, Melody E.] NCI, Lab Genom Divers, SAIC Frederick Inc, Frederick, MD 21701 USA. [Frank, Laurence G.] Univ Calif Berkeley, Living Lions Project Kenya, Museum Vertebrate Zool, Berkeley, CA 94720 USA. RP Shrestha, B (reprint author), Tufts Univ, Sch Med, Dept Mol Physiol & Pharmacol, Comparat & Mol Pharmacogen Lab, Boston, MA 02111 USA. EM michael.court@tufts.edu OI Goldstone, Jared/0000-0002-9618-4961 FU United States Department of State; National Institute of General Medical Sciences [R01GM061834]; National Cancer Institute (NCI) [N01-CO-12400]; NCI Center for Cancer Research, National Institutes of Health (NIH) FX Binu Shrestha was supported by a Fulbright scholarship from the United States Department of State. This project was funded by grant R01GM061834 from the National Institute of General Medical Sciences, contract N01-CO-12400 from the National Cancer Institute (NCI), and by the Intramural Research Program, NCI Center for Cancer Research, National Institutes of Health (NIH). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH, nor does mention of trade names, commercial products, or organizations imply endorsement by the United States Government. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 35 TC 24 Z9 25 U1 0 U2 20 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 28 PY 2011 VL 6 IS 3 AR e18046 DI 10.1371/journal.pone.0018046 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 743XV UT WOS:000289053800014 PM 21464924 ER PT J AU Yin, HE Vosters, JL Roescher, N D'Souza, A Kurien, BT Tak, PP Chiorini, JA AF Yin, Hongen Vosters, Jelle L. Roescher, Nienke D'Souza, Anil Kurien, Biji T. Tak, Paul P. Chiorini, John A. TI Location of Immunization and Interferon-gamma Are Central to Induction of Salivary Gland Dysfunction in Ro60 Peptide Immunized Model of Sjogren's Syndrome SO PLOS ONE LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CELL-LINE; ANTI-RO; AUTOANTIGEN; MICE; MOUSE AB Introduction: Anti-Ro antibodies can be found in the serum of the majority of patients with Sjogren's syndrome (SS). Immunization with a 60-kDa Ro peptide has been shown to induce SS-like symptoms in mice. The aim of this study was to investigate factors involved in salivary gland (SG) dysfunction after immunization and to test whether the induction of SS could be improved. Methods: Ro60 peptide immunization was tested in Balb/c mice, multiple antigenic peptide (MAP)-Ro60 and Pertussis toxin (PTX) were tested in SJL/J mice. In addition, two injection sites were compared in these two strains: the abdominal area and the tailbase. Each group of mice was tested for a loss of SG function, SG lymphocytic infiltration, anti-Ro and anti-La antibody formation, and cytokine production in cultured cells or homogenized SG extracts. Results: Ro60 peptide immunization in the abdominal area of female Balb/c mice led to impaired SG function, which corresponded with increased Th1 cytokines (IFN-gamma and IL-12) systemically and locally in the SG. Moreover, changing the immunization conditions to MAP-Ro60 in the abdominal area, and to lesser extend in the tailbase, also led to impaired SG function in SJL/J mice. As was seen in the Balb/c mice, increased IFN-gamma in the SG draining lymph nodes accompanied the SG dysfunction. However, no correlation was observed with anti-MAP-Ro60 antibody titers, and there was no additional effect on disease onset or severity. Conclusions: Effective induction of salivary gland dysfunction after Ro60 peptide immunization depended on the site of injection. Disease induction was not affected by changing the immunization conditions. However, of interest is that the mechanism of action of Ro60 peptide immunization appears to involve an increase in Th1 cytokines, resulting in the induction of SG dysfunction. C1 [Yin, Hongen; Vosters, Jelle L.; Roescher, Nienke; Chiorini, John A.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA. [Vosters, Jelle L.; Roescher, Nienke; Tak, Paul P.] Univ Amsterdam, Acad Med Ctr, Div Clin Immunol & Rheumatol, NL-1105 AZ Amsterdam, Netherlands. [D'Souza, Anil; Kurien, Biji T.] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. RP Yin, HE (reprint author), Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA. EM jchiorini@dir.nidcr.nih.gov FU Dutch Arthritis Association [NR 07-1-406]; NIH, NIDCR FX This work is supported by a Dutch Arthritis Association grant [NR 07-1-406] to JLV and an NIH, NIDCR intramural research grant to JAC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 22 TC 10 Z9 11 U1 1 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 28 PY 2011 VL 6 IS 3 AR e18003 DI 10.1371/journal.pone.0018003 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 743XV UT WOS:000289053800011 PM 21464925 ER PT J AU Berezhkovskii, AM Dagdug, L AF Berezhkovskii, Alexander M. Dagdug, Leonardo TI Analytical treatment of biased diffusion in tubes with periodic dead ends SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID POROUS-MEDIA; CAVITIES AB Effective mobility and diffusion coefficient of a particle in a tube with identical periodic dead ends characterize the motion on large time scale, when the particle displacement significantly exceeds the tube period. We derive formulas that show how these transport coefficients depend on the driving force and the geometric parameters of the system. Numerical tests show that values of the transport coefficients obtained from Brownian dynamics simulations are in excellent agreement with our theoretical predictions. [doi:10.1063/1.3567187] C1 [Berezhkovskii, Alexander M.; Dagdug, Leonardo] NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. [Dagdug, Leonardo] Univ Autonoma Metropolitana Iztapalapa, Dept Fis, Mexico City 09340, DF, Mexico. RP Dagdug, L (reprint author), NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. EM dll@xanum.uam.mx FU National of Institutes of Health (NIH), Center for Information Technology FX We are grateful to Sergey Bezrukov, Yurii Makhnovskii, and Vladimir Zitserman for numerous illuminating discussions of different aspects of transport in the presence of entropy barriers. This study was supported by the Intramural Research Program of the National of Institutes of Health (NIH), Center for Information Technology. NR 24 TC 13 Z9 13 U1 0 U2 3 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 J9 J CHEM PHYS JI J. Chem. Phys. PD MAR 28 PY 2011 VL 134 IS 12 AR 124109 DI 10.1063/1.3567187 PG 8 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 745FN UT WOS:000289151400014 PM 21456647 ER PT J AU Clifford, PS Hart, N Rothman, RB Blough, BE Bratton, GR Wellman, PJ AF Clifford, P. Shane Hart, Nigel Rothman, Richard B. Blough, Bruce E. Bratton, Gerald R. Wellman, Paul J. TI Perinatal lead exposure alters locomotion induced by amphetamine analogs in rats SO LIFE SCIENCES LA English DT Article DE Body weight; Monoamine; Amphetamine; Lead; Locomotion ID COCAINE; DEPENDENCE; LACTATION; BEHAVIOR; RELEASE AB Aims: The precise neurochemical perturbations through which perinatal (gestation/lactation) lead exposure modifies the reinforcement efficacy of various psychoactive drugs (e.g., cocaine, opiates) are unknown. The present study considers the role of altered serotonin and dopamine functionality in perinatal lead-psychostimulant interactions. Main methods: Female rats were administered a 16-mg lead or a control solution (p.o.) for 30 days prior to breeding with non-exposed males. Lead exposure was discontinued at weaning (postnatal day [PND] 21). Starting at PND 120, male rats born to control or lead-exposed dams were injected with either PAL-287 or PAL-353, at doses of 0, 2, 4, 8, or 16 umol/kg (i.p.) with each dose given prior to an acute (45 min) locomotion test. Whereas PAL-287 is a potent releaser of serotonin, PAL-353 is not. Each drug induces comparable release of norepinephrine (NE) and of dopamine (DA). Key findings: Control and lead rats exhibited minimal locomotion to PAL-287. PAL-353 produced a dose-dependent activation of locomotion in control rats relative to the effects of PAL-287 in control rats. Lead-exposed rats exhibited a subsensitivity to PAL-353 at doses of 4 and 8 umol/kg. Significance: The subsensitivity of lead rats to PAL-353 is consistent with a lead-induced diminution of dopamine function, an effect noted earlier for the reuptake inhibitor cocaine (Nation et al. 2000). The similar response of lead and control rats to PAL-287 is inconsistent with diminished serotonin function. (c) 2011 Elsevier Inc. All rights reserved. C1 [Clifford, P. Shane; Hart, Nigel; Wellman, Paul J.] Texas A&M Univ, Behav Neurosci Program, Dept Psychol, College Stn, TX 77843 USA. [Rothman, Richard B.] NIDA, Clin Psychopharmacol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Blough, Bruce E.] RTI Int, Sci & Engn Grp, Ctr Organ & Med Chem, Res Triangle Pk, NC 27709 USA. RP Wellman, PJ (reprint author), Texas A&M Univ, Behav Neurosci Program, Dept Psychol, College Stn, TX 77843 USA. EM PJW@PSYC.TAMU.EDU FU NIDA [R21 DA017230-01, R01 DA012970]; NIDA, NIH; DHHS FX The present study was supported by NIDA R21 DA017230-01 (P.J.W.) by NIDA R01 DA012970 (B.E.B.) and by the Intramural Research Program, NIDA, NIH and DHHS (R.B.R.). The authors thank Sam Buckman for his valuable technical assistance. NR 22 TC 1 Z9 1 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD MAR 28 PY 2011 VL 88 IS 13-14 BP 586 EP 589 DI 10.1016/j.lfs.2011.01.007 PG 4 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 740UI UT WOS:000288819500004 PM 21256854 ER PT J AU Chege, D Sheth, PM Kain, T Kim, CJ Kovacs, C Loutfy, M Halpenny, R Kandel, G Chun, TW Ostrowski, M Kaul, R AF Chege, Duncan Sheth, Prameet M. Kain, Taylor Kim, Connie J. Kovacs, Colin Loutfy, Mona Halpenny, Roberta Kandel, Gabor Chun, Tae-Wook Ostrowski, Mario Kaul, Rupert CA Toronto Mucosal Immunology Grp TI Sigmoid Th17 populations, the HIV latent reservoir, and microbial translocation in men on long-term antiretroviral therapy SO AIDS LA English DT Article DE antiretroviral therapy; microbial translocation; provirus; sigmoid colon; Th17 cells ID IMMUNODEFICIENCY-VIRUS-INFECTION; DEFICIENCY SYNDROME AIDS; T-CELL RESPONSES; LYMPHOID-TISSUE; IMMUNE ACTIVATION; PLASMA-LEVELS; VIRAL LOAD; RESTORATION; RECONSTITUTION; INFLAMMATION AB Objective: Th17 cells play an important role in mucosal defence and repair and are highly susceptible to infection by HIV. Antiretroviral therapy (ART) suppresses HIV viremia and can restore CD4(+) numbers in the blood and gastrointestinal mucosa, but the resolution of systemic inflammation and gut microbial translocation is often incomplete. We hypothesized that this might relate to persistent dysregulation of gut CD4(+) Th17 subsets. Methods: Blood and sigmoid biopsies were collected from HIV-uninfected men, chronically HIV-infected, ART-naive men, and men on effective ART for more than 4 years. Sigmoid provirus levels were assayed blind to participant status, as were CD4(+) Th17 subsets, systemic markers of microbial translocation, and cellular immune activation. Results: There was minimal CD4(+) Th17 dysregulation in the blood until later stage HIV infection, but gastrointestinal Th17 depletion was apparent much earlier, along with increased plasma markers of microbial translocation. Plasma lipopolysaccharide (LPS) remained elevated despite overall normalization of sigmoid Th17 populations on long-term ART, although there was considerable inter individual variability in Th17 reconstitution. An inverse correlation was observed between plasma LPS levels and gut Th17 frequencies, and higher plasma LPS levels correlated with an increased gut HIV proviral reservoir. Conclusion: Sigmoid Th17 populations were preferentially depleted during HIV infection. Despite overall CD4(+) T-cell reconstitution, sigmoid Th17 frequencies after long-term ART were heterogeneous and higher frequencies were correlated with reduced microbial translocation. (c) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins C1 [Chege, Duncan; Sheth, Prameet M.; Kain, Taylor; Kim, Connie J.; Loutfy, Mona; Ostrowski, Mario; Kaul, Rupert] Univ Toronto, Dept Med, Toronto, ON M5S 1A8, Canada. [Ostrowski, Mario; Kaul, Rupert] Univ Toronto, Dept Immunol, Toronto, ON M5S 1A8, Canada. [Kovacs, Colin; Loutfy, Mona] Univ Toronto, Maple Leaf Med Clin, Toronto, ON M5S 1A8, Canada. [Loutfy, Mona; Halpenny, Roberta] Womens Coll Hosp, Dept Med, Toronto, ON M5S 1B2, Canada. [Halpenny, Roberta; Kandel, Gabor; Ostrowski, Mario] St Michaels Hosp, Toronto, ON M5B 1W8, Canada. [Halpenny, Roberta; Kaul, Rupert] Univ Hlth Network, Toronto, ON, Canada. [Chun, Tae-Wook] Natl Inst Allergy & Dis, Immunoregulat Lab, NIH, Bethesda, MD USA. RP Chege, D (reprint author), Univ Toronto, Dept Med, Med Sci Bldg,Room 6356, Toronto, ON M5S 1A8, Canada. FU Ontario HIV Treatment Network [ROGB-G123]; Ontario Graduate Student Science & Technology/Canadian Institutes of Health Research; Canadian Research Chair Program FX We would like to thank Dr Lyle McKinnon, Dr David Willer, Dr Ali Sakhdari, and Ms Bahareh Vali for helpful proofing of this manuscript. This work was supported in part by the Ontario HIV Treatment Network (R. K., ROGB-G123; P. M. S., salary award); the Ontario Graduate Student Science & Technology Scholarships/Canadian Institutes of Health Research - Banting and Best Scholarship (D. C. salary) and the Canadian Research Chair Program (R. K., salary support). Study sponsors played no role in study design, collection or analysis of data, interpretation of results, writing of the manuscript or decision to submit for publication. NR 38 TC 64 Z9 65 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAR 27 PY 2011 VL 25 IS 6 BP 741 EP 749 DI 10.1097/QAD.0b013e328344cefb PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 736IR UT WOS:000288487400003 PM 21378536 ER PT J AU Musselwhite, LW Sheikh, V Norton, TD Rupert, A Porter, BO Penzak, SR Skinner, J Mican, JM Hadigan, C Sereti, I AF Musselwhite, Laura W. Sheikh, Virginia Norton, Thomas D. Rupert, Adam Porter, Brian O. Penzak, Scott R. Skinner, Jeff Mican, JoAnn M. Hadigan, Colleen Sereti, Irini TI Markers of endothelial dysfunction, coagulation and tissue fibrosis independently predict venous thromboembolism in HIV SO AIDS LA English DT Article DE blood coagulation factors; fibrosis; HIV; hyaluronic acid; P-selectin; venous thrombosis ID ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; INCIDENT CARDIOVASCULAR-DISEASE; D-DIMER; P-SELECTIN; IMMUNE ACTIVATION; INFECTED INDIVIDUALS; THROMBOSIS; MORTALITY; METAANALYSIS AB Objective: HIV infection is associated with coagulation abnormalities and significantly increased risk of venous thrombosis. It has been shown that higher plasma levels of coagulation and inflammatory biomarkers predicted mortality in HIV. We investigated the relationship between venous thrombosis and HIV-related characteristics, traditional risk factors of hypercoagulability, and pre-event levels of biomarkers. Design: A retrospective case-control study of 23 HIV-infected individuals who experienced an incident venous thromboembolic event while enrolled in National Institutes of Health studies from 1995 to 2010 and 69 age-matched and sex-matched HIV-infected individuals without known venous thromboembolism (VTE). Methods: Biomarkers of inflammation, endothelial dysfunction, coagulation, tissue fibrosis, and cytomegalovirus (CMV) reactivation were assessed by ELISA-based assays and PCR using plasma obtained prior to the event. Results: VTE events were related to nadir CD4 cell count, lifetime history of multiple opportunistic infections, CMV disease, CMV viremia, immunological AIDS, active infection, and provocation (i.e., recent hospitalization, surgery, or trauma). VTE events were independently associated with increased plasma levels of P-selectin (P = 0.002), D-dimer (P = 0.01), and hyaluronic acid (P = 0.009) in a multivariate analysis. No significant differences in antiretroviral or interleukin-2 exposures, plasma HIV viremia, or other traditional risk factors were observed. Conclusion: Severe immunodeficiency, active infection, and provocation are associated with venous thromboembolic disease in HIV. Biomarkers of endothelial dysfunction, coagulation, and tissue fibrosis may help identify HIV-infected patients at elevated risk of VTE. (c) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins C1 [Musselwhite, Laura W.; Sheikh, Virginia; Norton, Thomas D.; Porter, Brian O.; Penzak, Scott R.; Skinner, Jeff; Mican, JoAnn M.; Hadigan, Colleen; Sereti, Irini] NIAID, NIH, Bethesda, MD 20892 USA. [Rupert, Adam] NCI, AIDS Monitoring Lab, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21701 USA. RP Sereti, I (reprint author), NIAID, NIH, 10 Ctr Dr,Bldg 10,Room 11B07A, Bethesda, MD 20892 USA. EM isereti@niaid.nih.gov OI Musselwhite, Laura/0000-0003-0505-801X; Skinner, Jeff/0000-0001-5697-0442 FU NIH, NIAID; Critical Care Medicine Department; National Cancer Institute; NIH [HHSN261200800001E]; Pfizer Inc. FX This study was funded by the Intramural Program of the NIH, NIAID, Critical Care Medicine Department, and with federal funds from the National Cancer Institute, NIH, under contract number 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 US Government.; L. W. M. was a 2009-2010 participant in the Clinical Research Training Program, a public-private partnership supported jointly by the NIH and Pfizer Inc. via a grant to the Foundation for NIH from Pfizer Inc. NR 55 TC 32 Z9 32 U1 0 U2 3 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 MAR 27 PY 2011 VL 25 IS 6 BP 787 EP 795 DI 10.1097/QAD.0b013e3283453fcb PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 736IR UT WOS:000288487400008 PM 21412059 ER PT J AU Chun, TW Moir, S Kovacs, C Fauci, AS AF Chun, Tae-Wook Moir, Susan Kovacs, Colin Fauci, Anthony S. TI Rebound of plasma viremia following cessation of antiretroviral therapy despite profoundly low levels of HIV reservoir: implications for eradication Reply SO AIDS LA English DT Letter ID PROGENITOR CELLS; INFECTION C1 [Chun, Tae-Wook; Moir, Susan; Fauci, Anthony S.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Kovacs, Colin] Univ Toronto, Dept Med, Toronto, ON, Canada. 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PD MAR 27 PY 2011 VL 241 MA 308-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 782BO UT WOS:000291982801932 ER PT J AU Oquare, BY Micklitsch, CM Appella, DH AF Oquare, Bereket Yemane Micklitsch, Christopher M. Appella, Daniel H. TI Peptide nucleic acid (PNA) agents for anthrax detection SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 241st National Meeting and Exposition of the American-Chemical-Society (ACS) CY MAR 27-31, 2011 CL Anaheim, CA SP Amer Chem Soc ID DNA C1 [Oquare, Bereket Yemane; Micklitsch, Christopher M.; Appella, Daniel H.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 27 PY 2011 VL 241 MA 290-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 782BO UT WOS:000291982806263 ER PT J AU Pamment, M Pepe, A Kim, YS Lee, S Alarcon, S Trepel, J Malhotra, SV AF Pamment, Michael Pepe, Antonella Kim, Yeong Sang Lee, Sunmin Alarcon, Sylvia Trepel, Jane Malhotra, Sanjay V. TI Dihydropyridone derived library of androgen receptor modulators SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 241st National Meeting and Exposition of the American-Chemical-Society (ACS) CY MAR 27-31, 2011 CL Anaheim, CA SP Amer Chem Soc C1 Natl Canc Inst Frederick, Lab Synthet Chem, SAIC Frederick Inc, Frederick, MD USA. NCI, Med Oncol Branch, Ctr Canc Res, NIH,DHHS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 27 PY 2011 VL 241 MA 127-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 782BO UT WOS:000291982806118 ER PT J AU Peprah, K Eyunni, SVK Etukala, RJ Zhu, XY Setola, V Roth, BL Ablodeppey, SY AF Peprah, Kwakye Eyunni, Suresh V. K. Etukala, Reddy J. Zhu, Xue Y. Setola, Vincent Roth, Bryan L. Ablodeppey, Seth Y. TI Multi-receptor strategies io improve management of ailments of mental origin SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 241st National Meeting and Exposition of the American-Chemical-Society (ACS) CY MAR 27-31, 2011 CL Anaheim, CA SP Amer Chem Soc C1 Florida A&M Univ, Coll Pharm & Pharmaceut Sci, Tallahassee, FL 32307 USA. Univ N Carolina, NIMH PDSP Pharmacol, Chapel Hill, NC USA. RI Roth, Bryan/F-3928-2010 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 27 PY 2011 VL 241 MA 296-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 782BO UT WOS:000291982806268 ER PT J AU Pfefferkorn, CM Heinrich, F Sodt, AJ Pastor, RW Lee, JC AF Pfefferkorn, Candace M. Heinrich, Frank Sodt, Alex J. Pastor, Richard W. Lee, Jennifer C. TI Studying the alpha-synuclein membrane interface by photons and neutrons SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 241st National Meeting and Exposition of the American-Chemical-Society (ACS) CY MAR 27-31, 2011 CL Anaheim, CA SP Amer Chem Soc C1 NHLBI, Lab Mol Biophys, NIH, Bethesda, MD USA. NIST, Ctr Neutron Res, Gaithersburg, MD USA. Carnegie Mellon Univ, Dept Phys, Pittsburgh, PA 15213 USA. NHLBI, Lab Computat Biol, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 27 PY 2011 VL 241 MA 109-PHYS PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 782BO UT WOS:000291982801750 ER PT J AU Robbins, JB AF Robbins, John B. TI Conjugate technology applied to lipopolysaccharides of enteric pathogens SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 241st National Meeting and Exposition of the American-Chemical-Society (ACS) CY MAR 27-31, 2011 CL Anaheim, CA SP Amer Chem Soc C1 [Robbins, John B.] NICHD, Dept Lab Dev & Mol Immun, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 27 PY 2011 VL 241 MA 126-CARB PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 782BO UT WOS:000291982801662 ER PT J AU Rosenthal, AS Tanega, C Shen, M Mott, BT Austin, CP Auld, D Maloney, DJ Thomas, CJ AF Rosenthal, Andrew S. Tanega, Cordelle Shen, Min Mott, Bryan T. Austin, Christopher P. Auld, Douglas Maloney, David J. Thomas, Craig J. TI Potent and selective small molecule in vitro inhibitors of cdc2-like (CLK) and dual specificity tyrosine-phosphorylation-regulated (DYRK) kinases SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 241st National Meeting and Exposition of the American-Chemical-Society (ACS) CY MAR 27-31, 2011 CL Anaheim, CA SP Amer Chem Soc C1 [Rosenthal, Andrew S.; Tanega, Cordelle; Shen, Min; Mott, Bryan T.; Austin, Christopher P.; Auld, Douglas; Maloney, David J.; Thomas, Craig J.] NIH, Chem Genom Ctr, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 27 PY 2011 VL 241 MA 326-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 782BO UT WOS:000291982806024 ER PT J AU Sampson, DM Etukala, JR Kumar, EVKS Setola, V Roth, BL Ablordeppey, SY AF Sampson, Dinithia M. Etukala, Jagan R. Kumar, Eyunni V. K. Suresh Setola, Vincent Roth, Bryan L. Ablordeppey, Seth Y. TI Toward benzoxazole heterocycles exhibiting atypical antipsychotic binding affinity SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 241st National Meeting and Exposition of the American-Chemical-Society (ACS) CY MAR 27-31, 2011 CL Anaheim, CA SP Amer Chem Soc C1 Florida A&M Univ, Coll Pharm & Pharmaceut Sci, Tallahassee, FL 32307 USA. Univ N Carolina, Sch Med, Dept Pharmacol Med Chem & Psychiat, Chapel Hill, NC USA. Univ N Carolina, Sch Med, NIMH Psychoact Drug Screening Program, Chapel Hill, NC USA. RI Roth, Bryan/F-3928-2010 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 27 PY 2011 VL 241 MA 70-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 782BO UT WOS:000291982806069 ER PT J AU Sil, BC Cook, KM Schofield, C Figg, WD Hilton, ST AF Sil, Bruno C. Cook, Kristina M. Schofield, Christopher Figg, William D. Hilton, Stephen T. TI Novel multi-component approaches towards dimeric epidithiodiketopiperazines as anti-cancer agents SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 241st National Meeting and Exposition of the American-Chemical-Society (ACS) CY MAR 27-31, 2011 CL Anaheim, CA SP Amer Chem Soc C1 Univ London, Sch Pharm, Dept Pharmaceut & Biol Chem, London WC1N 1AX, England. Univ Oxford, Dept Chem, Oxford, England. NIH, Bethesda, MD 20892 USA. RI Cook, Kristina/B-8012-2008; Figg Sr, William/M-2411-2016 OI Cook, Kristina/0000-0002-0503-7166; NR 0 TC 0 Z9 0 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 27 PY 2011 VL 241 MA 272-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 782BO UT WOS:000291982806245 ER PT J AU Tabor, DC AF Tabor, Derrick C. TI Can the National Institutes of Health assist you in developing your career? SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 241st National Meeting and Exposition of the American-Chemical-Society (ACS) CY MAR 27-31, 2011 CL Anaheim, CA SP Amer Chem Soc C1 [Tabor, Derrick C.] Natl Inst Minor Hlth & Hlth Dispar, Ctr Excellence Program, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 27 PY 2011 VL 241 MA 5-SOCED PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 782BO UT WOS:000291982805005 ER PT J AU Tao, P Hodoscek, M Larkin, JD Shao, YH Brooks, BR AF Tao, Peng Hodoscek, Milan Larkin, Joseph D. Shao, Yihan Brooks, Bernard R. TI Comparison of reaction path methods using restraints, holonomic constraints, and nudged elastic band in study of inhibition mechanism of matrix metalloproteinase 2 (MMP2) by its potent inhibitor SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 241st National Meeting and Exposition of the American-Chemical-Society (ACS) CY MAR 27-31, 2011 CL Anaheim, CA SP Amer Chem Soc C1 NHLBI, NIH, Rockville, MD USA. Q Chem Inc, Design Ctr, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 27 PY 2011 VL 241 MA 271-COMP PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 782BO UT WOS:000291982804048 ER PT J AU Thatikonda, SK Kecskes, M Deflorian, F Yoo, LS Phan, K Mishra, S Gao, ZG Trenkle, W Jacobson, KA AF Thatikonda, Santhosh K. Kecskes, Miklos Deflorian, Francesca Yoo, Lena S. Khai Phan Mishra, Shilpi Gao, Zhan-Guo Trenkle, William Jacobson, Kenneth A. TI Molecular probes for the A(2A) adenosine receptor based on a pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine scaffold SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 241st National Meeting and Exposition of the American-Chemical-Society (ACS) CY MAR 27-31, 2011 CL Anaheim, CA SP Amer Chem Soc C1 [Thatikonda, Santhosh K.; Kecskes, Miklos; Deflorian, Francesca; Yoo, Lena S.; Khai Phan; Mishra, Shilpi; Gao, Zhan-Guo; Trenkle, William; Jacobson, Kenneth A.] NIDDKD, NIH, Bethesda, MD 20892 USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 27 PY 2011 VL 241 MA 18-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 782BO UT WOS:000291982804509 ER PT J AU Thomas, CJ AF Thomas, Craig J. TI Accessible technologies for the discovery of small molecules as research tools and clinical agents SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 241st National Meeting and Exposition of the American-Chemical-Society (ACS) CY MAR 27-31, 2011 CL Anaheim, CA SP Amer Chem Soc C1 [Thomas, Craig J.] NHGRI, Dept Chem, NIH Chem Genom Ctr, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 27 PY 2011 VL 241 MA 185-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 782BO UT WOS:000291982806164 ER PT J AU Ascierto, PA De Maio, E Bertuzzi, S Palmieri, G Halaban, R Hendrix, M Kashani-Sabet, M Ferrone, S Wang, E Cochran, A Rivoltini, L Lee, PP Fox, BA Kirkwood, JM Ullmann, CD Lehmann, FF Sznol, M Schwartzentruber, DJ Maio, M Flaherty, K Galon, J Ribas, A Yang, J Stroncek, DF Mozzillo, N Marincola, FM AF Ascierto, Paolo A. De Maio, Eleonora Bertuzzi, Stefano Palmieri, Giuseppe Halaban, Ruth Hendrix, Mary Kashani-Sabet, Mohamed Ferrone, Soldano Wang, Ena Cochran, Alistair Rivoltini, Licia Lee, Peter P. Fox, Bernard A. Kirkwood, John M. Ullmann, Claudio Dansky Lehmann, Frederic F. Sznol, Mario Schwartzentruber, Douglas J. Maio, Michele Flaherty, Keith Galon, Jerome Ribas, Antoni Yang, James Stroncek, David F. Mozzillo, Nicola Marincola, Franco M. TI Future perspectives in melanoma research. Meeting report from the "Melanoma Research: a bridge Naples-USA. Naples, December 6(th)-7(th) 2010" SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Review ID PRIMARY CUTANEOUS MELANOMA; PROGNOSTIC-SIGNIFICANCE; COLORECTAL-CANCER; CELLS; PROTEIN; TUMORS AB Progress in understanding the molecular basis of melanoma has made possible the identification of molecular targets with important implications in clinical practice. In fact, new therapeutic approaches are emerging from basic science and it will be important to implement their rapid translation into clinical practice by active clinical investigation. The first meeting of Melanoma Research: a bridge Naples-USA, organized by Paolo A. Ascierto (INT, Naples, Italy) and Francesco Marincola (NIH, Bethesda, USA) took place in Naples, on 6-7 December 2010. This international congress gathered more than 30 international and Italian faculty members and was focused on recent advances in melanoma molecular biology, immunology and therapy, and created an interactive discussion across Institutions belonging to Government, Academy and Pharmaceutical Industry, in order to stimulate new approaches in basic, translational and clinical research. Four topics of discussion were identified: New pathways in Melanoma, Biomarkers, Clinical Trials and New Molecules and Strategies. C1 [Ascierto, Paolo A.; De Maio, Eleonora; Mozzillo, Nicola] Fdn Pascale, Ist Nazl Tumori, Dept Melanoma Sarcoma & Head & Neck Dis, Naples, Italy. [Bertuzzi, Stefano] NIH, Off Director, Off Sci Policy Anal, Off Sci Policy, Bethesda, MD 20892 USA. [Palmieri, Giuseppe] CNR, Inst Biomol Chem, Unit Canc Genet, Sassari, Italy. [Halaban, Ruth] Yale Univ, Sch Med, Dept Dermatol, New Haven, CT 06510 USA. [Hendrix, Mary] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Feinberg Sch Med, Chicago, IL 60611 USA. [Kashani-Sabet, Mohamed] Calif Pacific Med Ctr, Res Inst, Ctr Melanoma Res & Treatment, San Francisco, CA USA. [Ferrone, Soldano] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Wang, Ena; Stroncek, David F.; Marincola, Franco M.] NIH, IDIS, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Wang, Ena; Stroncek, David F.; Marincola, Franco M.] NIH, Ctr Human Immunol, Bethesda, MD 20892 USA. [Cochran, Alistair] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Rivoltini, Licia] IRCCS Fdn, Ist Nazl Tumori, Unit Immunotherapy Human Tumors, Milan, Italy. [Lee, Peter P.] Stanford Univ, Dept Med, Stanford, CA 94305 USA. [Fox, Bernard A.] Providence Portland Med Ctr, Lab Mol & Tumor Immunol, Robert W Franz Canc Res Ctr, Earle A Chiles Res Inst, Portland, OR USA. [Fox, Bernard A.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. [Kirkwood, John M.] Univ Pittsburgh, Dept Med, Div Hematol Oncol, Inst Canc, Pittsburgh, PA USA. [Kirkwood, John M.] Pittsburgh Canc Inst, Melanoma Program, Pittsburgh, PA 15213 USA. [Ullmann, Claudio Dansky] NCI, Clin Invest Branch, Canc Therapy Evaluat Program DCTD, Bethesda, MD 20892 USA. [Lehmann, Frederic F.] GlaxoSmithKline Biol, Canc Immunotherapeut Business Unit, Rixensart, Belgium. [Sznol, Mario] Yale Canc Ctr, New Haven, CT USA. [Schwartzentruber, Douglas J.] Indiana Univ, Hlth Goshen Ctr Canc Care, Goshen, IN USA. [Maio, Michele] Univ Siena, Hosp Siena, Ist Toscano Tumori, I-53100 Siena, Italy. [Flaherty, Keith] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Galon, Jerome] INSERM, U872, Cordeliers Res Ctr, Inserm Grp Leader,Team 15, Paris, France. [Ribas, Antoni] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Dept Med, Los Angeles, CA 90024 USA. [Yang, James] NIH, Bethesda, MA USA. RP Ascierto, PA (reprint author), Fdn Pascale, Ist Nazl Tumori, Dept Melanoma Sarcoma & Head & Neck Dis, Naples, Italy. EM paolo.ascierto@gmail.com RI altomonte, maresa/G-7734-2011 FU Italian Ministry of Health [M2/11]; Fondazione Melanoma Onlus; Bristol Myers Squibb FX This work was supported by the Italian Ministry of Health "Progetto Ricerca Corrente Istituto Nazionale Tumori Pascale M2/11 Approccio multidisciplinare dalla ricerca alla cura del melanoma" and by Fondazione Melanoma Onlus. Authors would like to thank authors who have provided Tables originally published in Cancer Vaccines, Second Edition (2011) edited by Adrian Bot, Mihail Obrocea, and Franco Marincola; available from Informa Healthcare http://informahealthcare.com/.; PAA participated in advisory board for Bristol Myers Squibb, Merck/Schering-Plough, GlaxoSmithKline and Roche. MKS has served on the Merck/Schering-Plough Advisory Board and Speakers' Bureau, and owns stock in Melanoma Diagnostics. Myriad Genetics has licensed intellectual property developed by MKS. JMK is consultant to GSKbio and Morphotek. FFL is employee of GlaxoSmithKline Biologicals. MS received consulting fees from Bristol Myers Squibb. KF is consultant to Roche/Genentech and GlaxoSmithKline. AR participated in advisory board for Roche-Genentech and Bristol Myers Squibb. NR 28 TC 8 Z9 8 U1 0 U2 0 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 MAR 26 PY 2011 VL 9 AR 32 DI 10.1186/1479-5876-9-32 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 750RE UT WOS:000289564900001 PM 21439082 ER PT J AU Shiba, Y Randazzo, PA AF Shiba, Yoko Randazzo, Paul A. TI GEFH1 binds ASAP1 and regulates podosome formation SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE ASAP1; GEFH1; Podosome; ArfGAP ID NUCLEOTIDE EXCHANGE FACTOR; GTPASE-ACTIVATING PROTEIN; ARF GAPS; ACTIN CYTOSKELETON; RHO-GTPASES; INVADOPODIA; OSTEOCLASTS; GEF-H1; SRC AB Invadopodia are cellular structures that are thought to mediate tumor invasion. ASAP1, an Arf GTPase-activating protein (GAP) containing a BAR domain, is a substrate of Src. ASAP1 is required for the assembly of invadopodia and podosomes, which are Src-induced structures related to invadopodia in NIH 3T3 fibroblasts. The BAR domain of ASAP1 is required for the assembly of podosomes. Using two-hybrid screening, we have identified GEFH1, a guanine nucleotide exchange factor for RhoA, as a binding partner of the BAR domain of ASAP]. We validated the interaction of endogenous GEFH1 with ASAP1 by immunoprecipitation, and found GEFH1 colocalized with ASAP1 in podosomes. The overexpression of GEFH1 inhibited podosome assembly and ASAP1 catalytic activity as a GAP. A mutant of GEFH1 lacking the domain that binds to the BAR domain of ASAP] was less effective. Reduced expression of GEFH1, achieved with siRNA treatment, did not affect matrix degradation by podosomes but increased the rate of podosome assembly. Based on these results, we conclude that GEFH1 is a negative regulator of podosomes. Published by Elsevier Inc. C1 [Shiba, Yoko; Randazzo, Paul A.] NCI, Lab Cellular & Mol Biol, NIH, Bethesda, MD 20892 USA. RP Randazzo, PA (reprint author), NCI, Lab Cellular & Mol Biol, NIH, Bldg 37 Room 2042, Bethesda, MD 20892 USA. EM randazzp@mail.nih.gov FU National Cancer Institute, NIH FX This work was supported by the intramural program of the National Cancer Institute, NIH. NR 19 TC 5 Z9 6 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 25 PY 2011 VL 406 IS 4 BP 574 EP 579 DI 10.1016/j.bbrc.2011.02.093 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 743RO UT WOS:000289036600015 PM 21352810 ER PT J AU Collins, A Hewitt, SL Chaumeil, J Sellars, M Micsinai, M Allinne, J Parisi, F Nora, EP Bolland, DJ Corcoran, AE Kluger, Y Bosselut, R Ellmeier, W Chong, MMW Littman, DR Skok, JA AF Collins, Amelie Hewitt, Susannah L. Chaumeil, Julie Sellars, MacLean Micsinai, Mariann Allinne, Jeanne Parisi, Fabio Nora, Elphege P. Bolland, Dan J. Corcoran, Anne E. Kluger, Yuval Bosselut, Remy Ellmeier, Wilfried Chong, Mark M. W. Littman, Dan R. Skok, Jane A. TI RUNX Transcription Factor-Mediated Association of Cd4 and Cd8 Enables Coordinate Gene Regulation SO IMMUNITY LA English DT Article ID T-CELL LINEAGE; THYMOCYTE DIFFERENTIATION; LYMPHOCYTE DEVELOPMENT; IMMUNOGLOBULIN LOCI; X-INACTIVATION; B-CELLS; EXPRESSION; COMMITMENT; SILENCER; ENHANCER AB T cell fate is associated with mutually exclusive expression of CD4 or CD8 in helper and cytotoxic T cells, respectively. How expression of one locus is temporally coordinated with repression of the other has been a long-standing enigma, though we know RUNX transcription factors activate the Cd8 locus, silence the Cd4 locus, and repress the Zbtb7b locus (encoding the transcription factor ThPOK), which is required for CD4 expression. Here we found that nuclear organization was altered by interplay among members of this transcription factor circuitry: RUNX binding mediated association of Cd4 and Cd8 whereas ThPOK binding kept the loci apart. Moreover, targeted deletions within Cd4 modulated CD8 expression and pericentromeric repositioning of Cd8. Communication between Cd4 and Cd8 thus appears to enable long-range epigenetic regulation to ensure that expression of one excludes the other in mature CD4 or CD8 single-positive (SP) cells. C1 [Hewitt, Susannah L.; Chaumeil, Julie; Micsinai, Mariann; Allinne, Jeanne; Parisi, Fabio; Kluger, Yuval; Skok, Jane A.] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA. [Collins, Amelie; Sellars, MacLean; Chong, Mark M. W.; Littman, Dan R.] NYU, Sch Med, Kimmel Ctr Biol & Med, Mol Pathogenesis Program,Skirball Inst, New York, NY 10016 USA. [Micsinai, Mariann] NYU, Sch Med, Ctr Hlth Informat & Bioinformat, New York, NY 10016 USA. [Micsinai, Mariann] NYU, Sch Med, Inst Canc, New York, NY 10016 USA. [Micsinai, Mariann; Parisi, Fabio; Kluger, Yuval] Yale Univ, Sch Med, Yale Canc Ctr, New Haven, CT 06520 USA. [Nora, Elphege P.] Inst Curie, CNRS, INSERM, UMR3215,U934, F-75724 Paris 05, France. [Bolland, Dan J.; Corcoran, Anne E.] Babraham Inst, Cambridge CB22 3AT, England. [Bosselut, Remy] NCI, Lab Immune Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Ellmeier, Wilfried] Med Univ Vienna, Inst Immunol, Div Immunobiol, A-1090 Vienna, Austria. [Skok, Jane A.] UCL, Dept Immunol & Mol Pathol, Div Infect & Immun, London W1T 4JF, England. [Littman, Dan R.] UCL, Howard Hughes Med Inst, London W1T 4JF, England. RP Skok, JA (reprint author), NYU, Sch Med, Dept Pathol, 550 1st Ave, New York, NY 10016 USA. EM jane.skok@med.nyu.edu RI Chong, Mark/H-6684-2016; OI Nora, Elphege/0000-0002-8347-4396; Ellmeier, Wilfried/0000-0001-8192-8481; Skok, Jane/0000-0002-4145-1516 FU Leukemia and Lymphoma Scholar Award; NIH [1R01GM086852]; WT project [WT 085096]; Howard Hughes Medical Institute; Helen and Martin Kimmel Center for Biology and Medicine; American Society of Hematology; NSF [0333389]; Cancer Research Institute; Helen and Martin Kimmel Center for Stem Cell Biology; BBSRC (Biotechnology and Biological Sciences Research Council); Austrian Science Fund (FWF) [P19930]; National Cancer Institute, Center for Cancer Research, NIH FX We would like to thank J. de Nooij and T. Jessell for RUNX3 antibody (Kramer et al., 2006). We also thank members of the J.A.S. and D.R.L. labs for thoughtful discussions and critical comments on the manuscript. This work was supported by a Leukemia and Lymphoma Scholar Award, an NIH 1R01GM086852 grant, and a WT project grant (WT 085096) (J.A.S.). A.C. and D.R.L. were supported by funds from the Howard Hughes Medical Institute and from the Helen and Martin Kimmel Center for Biology and Medicine. S.L.H. is supported by a Fellow Scholar Award from the American Society of Hematology and M.M. is supported by NSF IGERT grant 0333389. M.M.W.C. was funded sequentially by a Postdoctoral Fellowship from the Cancer Research Institute and a Senior Fellowship from the Helen and Martin Kimmel Center for Stem Cell Biology. A.E.C. and D.J.B. are supported by a BBSRC project grant (Biotechnology and Biological Sciences Research Council). Work in the lab of W.E. is supported by the Austrian Science Fund (FWF; P19930). Work in the lab of R.B. is supported by the Intramural Research Program of the National Cancer Institute, Center for Cancer Research, NIH. M.S. is an Irvington Institute Fellow of the Cancer Research Institute. NR 48 TC 19 Z9 20 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAR 25 PY 2011 VL 34 IS 3 BP 303 EP 314 DI 10.1016/j.immuni.2011.03.004 PG 12 WC Immunology SC Immunology GA 743JL UT WOS:000289014500007 PM 21435585 ER PT J AU Pandiyan, P Conti, HR Zheng, LX Peterson, AC Mathern, DR Hernandez-Santos, N Edgerton, M Gaffen, SL Lenardo, MJ AF Pandiyan, Pushpa Conti, Heather R. Zheng, Lixin Peterson, Alanna C. Mathern, Douglas R. Hernandez-Santos, Nydiaris Edgerton, Mira Gaffen, Sarah L. Lenardo, Michael J. TI CD4(+)CD25(+)Foxp3(+) Regulatory T Cells Promote Th17 Cells In Vitro and Enhance Host Resistance in Mouse Candida albicans Th17 Cell Infection Model SO IMMUNITY LA English DT Article ID PROTECTIVE IMMUNITY; ORAL CANDIDIASIS; IL-17; INTERLEUKIN-2; AUTOIMMUNITY; GENERATION; RESPONSES; DEFENSE; HELPER AB Th17 cells and CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells are thought to promote and suppress inflammatory responses, respectively. Here we explore why under Th17 cell polarizing conditions, Treg cells did not suppress, but rather upregulated, the expression of interleukin-17A (IL-17A), IL-17F, and IL-22 from responding CD4(+) T cells (Tresp cells). Upregulation of IL-17 cytokines in Tresp cells was dependent on consumption of IL-2 by Treg cells, especially at early time points both in vitro and in vivo. During an oral Candida albicans infection in mice, Treg cells induced IL-17 cytokines in Tresp cells, which markedly enhanced fungal clearance and recovery from infection. These findings show how Treg cells can promote acute Th17 cell responses to suppress mucosal fungus infections and reveal that Treg cells have a powerful capability to fight infections besides their role in maintaining tolerance or immune homeostasis. C1 [Pandiyan, Pushpa; Zheng, Lixin; Mathern, Douglas R.; Lenardo, Michael J.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Conti, Heather R.; Edgerton, Mira; Gaffen, Sarah L.] SUNY Buffalo, Dept Oral Biol, Buffalo, NY 14214 USA. [Peterson, Alanna C.; Hernandez-Santos, Nydiaris; Gaffen, Sarah L.] Univ Pittsburgh, Dept Med, Div Rheumatol & Clin Immunol, Pittsburgh, PA 15261 USA. RP Lenardo, MJ (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM lenardo@nih.gov FU National Research Council (NRC); National Academy of Sciences; NIH [DE0188122]; National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH); [AR054389]; [DE007034] FX We thank R. Germain, A. Singer, Y. Belkaid, P. Schwartzberg, and A. Snow for critically reading the manuscript and C. Trageser, J. Lee, and other members of the M.J.L. laboratory for valuable suggestions and help. We also thank O. Schwartz and L. Koo for their help in microscopy and J. Edwards for FAGS sorting. P.P. was supported by a fellowship from the National Research Council (NRC) and National Academy of Sciences; S.L.G. and M.E. were supported by NIH grant DE0188122; and S.L.G. was also supported by AR054389. H.R.C. was supported by a training grant (DE007034) to the Department of Oral Biology. This work was supported by the intramural research program of National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH). P.P. designed the study, performed experiments, and analyzed data with the supervision of M.J.L. P.P. and M.J.L. wrote the manuscript; L.Z. measured the weight of the mice in blinded fashion and contributed to discussions; and D.R.M. helped P.P. in LPMC preparations in IBD experiments. S.L.G. and M.E. supported H.R.C. H.R.C. performed and helped P.P. in C. albicans infection experiments. NR 30 TC 119 Z9 127 U1 2 U2 9 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAR 25 PY 2011 VL 34 IS 3 BP 422 EP 434 DI 10.1016/j.immuni.2011.03.002 PG 13 WC Immunology SC Immunology GA 743JL UT WOS:000289014500017 PM 21435589 ER PT J AU Hall, JA Cannons, JL Grainger, JR Dos Santos, LM Hand, TW Naik, S Wohlfert, EA Chou, DB Oldenhove, G Robinson, M Grigg, ME Kastenmayer, R Schwartzberg, PL Belkaid, Y AF Hall, Jason A. Cannons, Jennifer L. Grainger, John R. Dos Santos, Liliane M. Hand, Timothy W. Naik, Shruti Wohlfert, Elizabeth A. Chou, David B. Oldenhove, Guillaume Robinson, Melody Grigg, Michael E. Kastenmayer, Robin Schwartzberg, Pamela L. Belkaid, Yasmine TI Essential Role for Retinoic Acid in the Promotion of CD4(+) T Cell Effector Responses via Retinoic Acid Receptor Alpha SO IMMUNITY LA English DT Article ID VITAMIN-A-DEFICIENCY; DENDRITIC CELLS; TOXOPLASMA-GONDII; SIGNALING PATHWAY; SMALL-INTESTINE; TH17 CELLS; FOXP3; DIFFERENTIATION; MICE; METABOLISM AB Vitamin A and its metabolite, retinoic acid (RA) are implicated in the regulation of immune homeostasis via the peripheral induction of regulatory T cells. Here we showed RA was also required to elicit proinflammatory CD4(+) helper T cell responses to infection and mucosal vaccination. Retinoic acid receptor alpha (RAR alpha) was the critical mediator of these effects. Antagonism of RAR signaling and deficiency in RAR alpha (Rara(-/-)) resulted in a cell-autonomous CD4(+) T cell activation defect, which impaired intermediate signaling events, including calcium mobilization. Altogether, these findings reveal a fundamental role for the RA-RAR alpha axis in the development of both regulatory and inflammatory arms of adaptive immunity and establish nutritional status as a broad regulator of adaptive T cell responses. C1 [Hall, Jason A.; Grainger, John R.; Dos Santos, Liliane M.; Hand, Timothy W.; Naik, Shruti; Wohlfert, Elizabeth A.; Chou, David B.; Oldenhove, Guillaume; Belkaid, Yasmine] NIAID, Mucosal Immun Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Cannons, Jennifer L.; Schwartzberg, Pamela L.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. [Robinson, Melody; Kastenmayer, Robin] NIAID, Comparat Med Branch, NIH, Bethesda, MD 20892 USA. [Grigg, Michael E.] NIAID, Mol Parasitol Unit, NIH, Bethesda, MD 20892 USA. [Hall, Jason A.; Naik, Shruti] Univ Penn, Immunol Grad Grp, Philadelphia, PA 19104 USA. RP Belkaid, Y (reprint author), NIAID, Mucosal Immun Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. EM ybelkaid@niaid.nih.gov OI Grainger, John/0000-0002-4052-5923 FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Office of Dietary Supplements FX This work was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health and the Office of Dietary Supplements. We thank K. Holmes, D. Stephany, and the NIAID sorting facility. We thank K. Beacht and the Comparative Medicine Branch animal for animal handling and technical assistance. We thank J. Clements for providing LT(R129G). We thank R. Schwartz, S.-Y. Choi, K. Laky, and D. Hildeman for experimental advice. Finally, we thank R. Bosselut and A. Sher for critical reading of the manuscript. NR 54 TC 153 Z9 157 U1 0 U2 9 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 MAR 25 PY 2011 VL 34 IS 3 BP 435 EP 447 DI 10.1016/j.immuni.2011.03.003 PG 13 WC Immunology SC Immunology GA 743JL UT WOS:000289014500018 PM 21419664 ER PT J AU Noinaj, N Fairman, JW Buchanan, SK AF Noinaj, Nicholas Fairman, James W. Buchanan, Susan K. TI The Crystal Structure of BamB Suggests Interactions with BamA and Its Role within the BAM Complex SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE YfgL; lipoprotein; beta-barrel membrane protein; protein folding; OMP biogenesis ID OUTER-MEMBRANE PROTEINS; WD-REPEAT PROTEINS; ESCHERICHIA-COLI; YAET COMPLEX; FLEXIBILITY; BIOGENESIS; SECRETION; COMPONENT; SOFTWARE; BACTERIA AB Escherichia coli BamB is the largest of four lipoproteins in the beta-barrel assembly machinery (BAM) complex. It interacts with the periplasmic domain of BamA, an integral outer membrane protein (OMP) essential for OMP biogenesis. Although BamB is not essential, it serves an important function in the BAM complex, significantly increasing the folding efficiency of some OMPs in vivo and in vitro. To learn more about the BAM complex, we solved structures of BamB in three different crystal forms. BamB crystallized in space groups P2(1)3, 1222, and P212121, with one molecule per asymmetric unit in each case. Crystals from the space group 1222 diffracted to 1. 65-angstrom resolution. BamB forms an eight-bladed beta-propeller with a central pore and is shaped like a doughnut. A DALI search revealed that BamB shares structural homology to several eukaryotic proteins containing WD40 repeat domains, which commonly have V.-propeller folds and often serve as scaffolding proteins within larger multi-protein complexes that carry out signal transduction, cell division, and chemotaxis. Using mutagenesis data from previous studies, we docked BamB onto a BamA structural model and assessed known and possible interactions between these two proteins. Our data suggest that BamB serves as a scaffolding protein within the BAM complex by optimally orienting the flexible periplasmic domain of BamA for interaction with other BAM components and chaperones. This may facilitate integration of newly synthesized OMPs into the outer membrane. Published by Elsevier Ltd. C1 [Noinaj, Nicholas; Fairman, James W.; Buchanan, Susan K.] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Buchanan, SK (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM skbuchan@helix.nih.gov FU NTH, National Institute of Diabetes and Digestive and Kidney Diseases; US Department of Energy, Office of Science, Office of Basic Energy Sciences [W-31-109-Eng-38]; US Department of Energy, Basic Energy Sciences, Office of Science [DE-ACO2-06CH11357] FX This research was supported by the Intramural Research Program of the NTH, National Institute of Diabetes and Digestive and Kidney Diseases. We would like to thank the respective staffs at the Southeast Regional Collaborative Access Team (SER-CAT) and General Medicine and Cancer Institutes Collaborative Access Team (GM/CACAT) beamlines at the Advanced Photon Source, Argonne National Laboratory, for their assistance during data collection. Use of the Advanced Photon Source was supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences, under contract no. W-31-109-Eng-38 (SERCAT), and by the US Department of Energy, Basic Energy Sciences, Office of Science, under contract no. DE-ACO2-06CH11357 (GM/CA-CAT). NR 43 TC 54 Z9 56 U1 0 U2 7 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 MAR 25 PY 2011 VL 407 IS 2 BP 248 EP 260 DI 10.1016/j.jmb.2011.01.042 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 742EW UT WOS:000288925100004 PM 21277859 ER PT J AU Nayak, TK Garmestani, K Milenic, DE Baidoo, KE Brechbiel, MW AF Nayak, Tapan K. Garmestani, Kayhan Milenic, Diane E. Baidoo, Kwamena E. Brechbiel, Martin W. TI HER1-Targeted Y-86-Panitumumab Possesses Superior Targeting Characteristics than Y-86-Cetuximab for PET Imaging of Human Malignant Mesothelioma Tumors Xenografts SO PLOS ONE LA English DT Article ID GROWTH-FACTOR-RECEPTOR; COPPER-64-LABELED MONOCLONAL-ANTIBODY; DISSEMINATED PERITONEAL DISEASE; PLEURAL MESOTHELIOMA; PHASE-II; CANCER; EXPRESSION; PROTEIN; MODEL; RADIOIMMUNOTHERAPY AB Malignant mesothelioma (MM), a rare form of cancer is often associated with previous exposure to fibrous minerals, such as asbestos. Asbestos exposure increases HER1-activity and expression in pre-clinical models. Additionally, HER1 over-expression is observed in the majority of MM cases. In this study, the utility of HER1-targeted chimeric IgG(1), cetuximab, and a human IgG(2), panitumumab, radiolabeled with Y-86, were evaluated for PET imaging to detect MM non-invasively in vivo, and to select an antibody candidate for radioimmunotherapy (RIT). Methods: Radioimmunoconjugates (RICs) of cetuximab and panitumumab were prepared by conjugation with CHX-A"-DTPA followed by radiolabeling with Y-86. The HER1 expression of NCI-H226, NCI-H2052, NCI-H2452 and MSTO-211H human mesothelioma cells was characterized by flow cytometry. In vivo biodistribution, pharmacokinetic analysis, and PET imaging were performed in tumor bearing athymic mice. Results: In vivo studies demonstrated high HER1 tumor uptake of both RICs. Significant reduction in tumor uptake was observed in mice co-injected with excess mAb (0.1 mg), demonstrating that uptake in the tumor was receptor specific. Significant differences were observed in the in vivo characteristics of the RICs. The blood clearance T1/2 alpha of Y-86-cetuximab (0.9-1.1 h) was faster than Y-86-panitumumab (2.6-3.1 h). Also, the tumor area under the curve (AUC) to liver AUC ratios of Y-86-panitumumab were 1.5 to 2.5 times greater than Y-86-cetuximab as observed by the differences in PET tumor to background ratios, which could be critical when imaging orthotopic tumors and concerns regarding radiation doses to normal organs such as the liver. Conclusion: This study demonstrates the more favorable HER1-targeting characteristics of Y-86-panitumumab than Y-86-cetuximab for non-invasive assessment of the HER1 status of MM by PET imaging. Due to lower liver uptake, panitumumab based immunoconjugates may fare better in therapy than corresponding cetuximab based immunoconjugates. C1 [Nayak, Tapan K.; Garmestani, Kayhan; Milenic, Diane E.; Baidoo, Kwamena E.; Brechbiel, Martin W.] NCI, Radiat Oncol Branch, NIH, Radioimmune & Inorgan Chem Sect, Bethesda, MD 20892 USA. RP Nayak, TK (reprint author), NCI, Radiat Oncol Branch, NIH, Radioimmune & Inorgan Chem Sect, Bldg 10, Bethesda, MD 20892 USA. EM tapann@gmail.com; martinwb@mail.nih.gov OI Nayak, Tapan/0000-0002-3706-6092 FU NIH; NCI; Center for Cancer Research; United States Department of Health and Human Services FX The Intramural Research Program of the NIH, NCI, Center for Cancer Research and the United States Department of Health and Human Services. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 42 TC 27 Z9 27 U1 0 U2 14 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 25 PY 2011 VL 6 IS 3 AR e18198 DI 10.1371/journal.pone.0018198 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 740SE UT WOS:000288813900050 PM 21464917 ER PT J AU Palmer, SM Flake, GP Kelly, FL Zhang, HL Nugent, JL Kirby, PJ Foley, JF Gwinn, WM Morgan, DL AF Palmer, Scott M. Flake, Gordon P. Kelly, Fran L. Zhang, Helen L. Nugent, Julia L. Kirby, Patrick J. Foley, Julie F. Gwinn, William M. Morgan, Dan L. TI Severe Airway Epithelial Injury, Aberrant Repair and Bronchiolitis Obliterans Develops after Diacetyl Instillation in Rats SO PLOS ONE LA English DT Article ID STEM-CELL TRANSPLANTATION; SECRETORY PROTEIN CC16; LUNG TRANSPLANTATION; BASEMENT-MEMBRANE; DECREASED SERUM; WORKERS; TENASCIN; UPDATE; ASTHMA; PLANT AB Background: Bronchiolitis obliterans (BO) is a fibrotic lung disease that occurs in a variety of clinical settings, including toxin exposures, autoimmunity and lung or bone marrow transplant. Despite its increasing clinical importance, little is known regarding the underlying disease mechanisms due to a lack of adequate small animal BO models. Recent epidemiological studies have implicated exposure to diacetyl (DA), a volatile component of artificial butter flavoring, as a cause of BO in otherwise healthy factory workers. Our overall hypothesis is that DA induces severe epithelial injury and aberrant repair that leads to the development of BO. Therefore, the objectives of this study were 1) to determine if DA, delivered by intratracheal instillation (ITI), would lead to the development of BO in rats and 2) to characterize epithelial regeneration and matrix repair after ITI of DA. Methods and Main Results: Male Sprague-Dawley rats were treated with a single dose of DA (125 mg/kg) or sterile water (vehicle control) by ITI. Instilled DA resulted in airway specific injury, followed by rapid epithelial regeneration, and extensive intraluminal airway fibrosis characteristic of BO. Increased airway resistance and lung fluid neutrophilia occurred with the development of BO, similar to human disease. Despite rapid epithelial regeneration after DA treatment, expression of the normal phenotypic markers, Clara cell secretory protein and acetylated tubulin, were diminished. In contrast, expression of the matrix component Tenascin C was significantly increased, particularly evident within the BO lesions. Conclusions: We have established that ITI of DA results in BO, creating a novel chemical-induced animal model that replicates histological, biological and physiological features of the human disease. Furthermore, we demonstrate that dysregulated epithelial repair and excessive matrix Tenacin C deposition occur in BO, providing new insights into potential disease mechanisms and therapeutic targets. C1 [Palmer, Scott M.; Kelly, Fran L.; Zhang, Helen L.; Nugent, Julia L.] Duke Univ, Med Ctr, Div Pulm & Crit Care Med, Durham, NC 27706 USA. [Flake, Gordon P.; Kirby, Patrick J.; Foley, Julie F.; Gwinn, William M.; Morgan, Dan L.] NIEHS, Res Triangle Pk, NC 27709 USA. RP Palmer, SM (reprint author), Duke Univ, Med Ctr, Div Pulm & Crit Care Med, Durham, NC 27706 USA. EM palme002@mc.duke.edu FU U.S. National Institutes of Health at the National Institute of Environmental Health Sciences (NIEHS); National Heart Lung Blood Institute [HL91140-01] FX This research was funded the U.S. National Institutes of Health through Intramural Research grants to DLM at the National Institute of Environmental Health Sciences (NIEHS) and SMP from National Heart Lung Blood Institute (grant HL91140-01). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 28 TC 28 Z9 32 U1 1 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 25 PY 2011 VL 6 IS 3 AR e17644 DI 10.1371/journal.pone.0017644 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 740SE UT WOS:000288813900004 PM 21464978 ER PT J AU Rothman, RB Cadet, JL Dersch, CM McCoy, MT Lehrmann, E Becker, KG Bader, M Alenina, N Baumann, MH AF Rothman, Richard B. Cadet, Jean L. Dersch, Christina M. McCoy, Michael T. Lehrmann, Elin Becker, Kevin G. Bader, Michael Alenina, Natalia Baumann, Michael H. TI Altered Gene Expression in Pulmonary Tissue of Tryptophan Hydroxylase-1 Knockout Mice: Implications for Pulmonary Arterial Hypertension SO PLOS ONE LA English DT Article ID 5-HYDROXYTRYPTAMINE TRANSPORTER GENE; VASCULAR SMOOTH-MUSCLE; SEROTONIN TRANSPORTER; PLASMA SEROTONIN; CARDIAC-FUNCTION; TRANSGENIC MICE; CHRONIC HYPOXIA; DEXFENFLURAMINE; FENFLURAMINE; RECEPTORS AB The use of fenfluramines can increase the risk of developing pulmonary arterial hypertension (PAH) in humans, but the mechanisms responsible are unresolved. A recent study reported that female mice lacking the gene for tryptophan hydroxylase-1 (Tph1(-/-) mice) were protected from PAH caused by chronic dexfenfluramine, suggesting a pivotal role for peripheral serotonin (5-HT) in the disease process. Here we tested two alternative hypotheses which might explain the lack of dexfenfluramine-induced PAH in Tph1(-/-) mice. We postulated that: 1) Tph1(-/-) mice express lower levels of pulmonary 5-HT transporter (SERT) when compared to wild-type controls, and 2) Tph1(-/-) mice display adaptive changes in the expression of non-serotonergic pulmonary genes which are implicated in PAH. SERT was measured using radioligand binding methods, whereas gene expression was measured using microarrays followed by quantitative real time PCR (qRT-PCR). Contrary to our first hypothesis, the number of pulmonary SERT sites was modestly up-regulated in female Tph1(-/-) mice. The expression of 51 distinct genes was significantly altered in the lungs of female Tph1(-/-) mice. Consistent with our second hypothesis, qRT-PCR confirmed that at least three genes implicated in the pathogenesis of PAH were markedly up-regulated: Has2, Hapln3 and Retlna. The finding that female Tph1(-/-) mice are protected from dexfenfluramine-induced PAH could be related to compensatory changes in pulmonary gene expression, in addition to reductions in peripheral 5-HT. These observations emphasize the intrinsic limitation of interpreting data from studies conducted in transgenic mice that are not fully characterized. C1 [Rothman, Richard B.; Dersch, Christina M.; Baumann, Michael H.] NIDA, Translat Pharmacol Sect, Intramural Res Program, NIH, Baltimore, MD USA. [Cadet, Jean L.; McCoy, Michael T.] NIDA, Mol Neuropsychiat Res Branch, Intramural Res Program, NIH, Baltimore, MD USA. [Lehrmann, Elin; Becker, Kevin G.] NIA, Gene Express & Genom Unit, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Bader, Michael; Alenina, Natalia] Max Delbruck Ctr Mol Med, Berlin, Germany. RP Rothman, RB (reprint author), NIDA, Translat Pharmacol Sect, Intramural Res Program, NIH, Baltimore, MD USA. EM rrothman@mail.nih.gov OI Lehrmann, Elin/0000-0002-9869-9475; Becker, Kevin/0000-0002-6794-6656; Bader, Michael/0000-0003-4780-4164 FU National Institute on Drug Abuse; National Institute on Aging, National Institutes of Health, DHHS FX This work was supported by the Intramural Research Programs, National Institute on Drug Abuse and the National Institute on Aging, National Institutes of Health, DHHS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 29 TC 5 Z9 5 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 MAR 25 PY 2011 VL 6 IS 3 AR e17735 DI 10.1371/journal.pone.0017735 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 740SE UT WOS:000288813900009 PM 21464983 ER PT J AU Bacolla, A Wang, GL Jain, A Chuzhanova, NA Cer, RZ Collins, JR Cooper, DN Bohr, VA Vasquez, KM AF Bacolla, Albino Wang, Guliang Jain, Aklank Chuzhanova, Nadia A. Cer, Regina Z. Collins, Jack R. Cooper, David N. Bohr, Vilhelm A. Vasquez, Karen M. TI Non-B DNA-forming Sequences and WRN Deficiency Independently Increase the Frequency of Base Substitution in Human Cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID WERNER-SYNDROME PROTEIN; SYNDROME RECQ HELICASE; HUMAN DHX9 HELICASE; GENETIC INSTABILITY; IN-VIVO; ELECTRON-TRANSFER; OXIDATIVE DAMAGE; REPLICATION FORK; AQUEOUS-SOLUTION; MAMMALIAN-CELLS AB Although alternative DNA secondary structures (non-B DNA) can induce genomic rearrangements, their associated mutational spectra remain largely unknown. The helicase activity of WRN, which is absent in the human progeroid Werner syndrome, is thought to counteract this genomic instability. We determined non-B DNA-induced mutation frequencies and spectra in human U2OS osteosarcoma cells and assessed the role of WRN in isogenic knockdown (WRN-KD) cells using a supF gene mutation reporter system flanked by triplex-or Z-DNA-forming sequences. Although both non-B DNA and WRN-KD served to increase the mutation frequency, the increase afforded by WRN-KD was independent of DNA structure despite the fact that purified WRN helicase was found to resolve these structures in vitro. In U2OS cells, similar to 70% of mutations comprised single-base substitutions, mostly at G.C base-pairs, with the remaining similar to 30% being microdeletions. The number of mutations at G.C base-pairs in the context of NGNN/NNCN sequences correlated well with predicted free energies of base stacking and ionization potentials, suggesting a possible origin via oxidation reactions involving electron loss and subsequent electron transfer (hole migration) between neighboring bases. A set of similar to 40,000 somatic mutations at G.C base pairs identified in a lung cancer genome exhibited similar correlations, implying that hole migration may also be involved. We conclude that alternative DNA conformations, WRN deficiency and lung tumorigenesis may all serve to increase the mutation rate by promoting, through diverse pathways, oxidation reactions that perturb the electron orbitals of neighboring bases. It follows that such "hole migration" is likely to play a much more widespread role in mutagenesis than previously anticipated. C1 [Bacolla, Albino; Wang, Guliang; Jain, Aklank; Vasquez, Karen M.] Univ Texas MD Anderson Canc Ctr, Div Sci Pk Res, Dept Mol Carcinogenesis, Smithville, TX 78957 USA. [Chuzhanova, Nadia A.] Nottingham Trent Univ, Sch Sci & Technol, Nottingham NG11 8NS, England. [Cer, Regina Z.; Collins, Jack R.] NCI, Adv Biomed Comp Ctr, SAIC Frederick Inc, Frederick, MD 21702 USA. [Cooper, David N.] Cardiff Univ, Sch Med, Inst Med Genet, Cardiff CF14 4XN, S Glam, Wales. [Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Vasquez, KM (reprint author), 1400 Barbara Jordan Blvd,R1800, Austin, TX 78723 USA. EM karen.vasquez@austin.utexas.edu RI Cooper, David/H-4384-2011; Bacolla, Albino/N-3877-2013; OI Cooper, David/0000-0002-8943-8484; Bacolla, Albino/0000-0003-0206-8423; Chuzhanova, Nadia/0000-0002-4655-3618 FU National Institutes of Health [CA093729, HHSN261200800001E]; National Institute of Environmental Health Sciences Center [P30ES007784]; National Institute on Aging, National Institutes of Heath; National Institutes of Health through M.D. Anderson Cancer Center [CA016672] FX This work was supported, in whole or in part, by National Institutes of Health Grants CA093729 (to K. M. V.) and HHSN261200800001E (to A. B.). This work was also supported by National Institute of Environmental Health Sciences Center Grant P30ES007784, by the Intramural Program of the National Institute on Aging, National Institutes of Heath, and by the National Institutes of Health through M.D. Anderson Cancer Center Support Grant CA016672. NR 70 TC 15 Z9 15 U1 1 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 25 PY 2011 VL 286 IS 12 BP 10017 EP 10026 DI 10.1074/jbc.M110.176636 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 737CU UT WOS:000288547000016 PM 21285356 ER PT J AU Sattlegger, E Barbosa, JARG Moraes, MCS Martins, RM Hinnebusch, AG Castilho, BA AF Sattlegger, Evelyn Barbosa, Joao A. R. G. Moraes, Maria Carolina S. Martins, Rafael M. Hinnebusch, Alan G. Castilho, Beatriz A. TI Gcn1 and Actin Binding to Yih1 IMPLICATIONS FOR ACTIVATION OF THE eIF2 KINASE GCN2 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE GCN2; ELONGATION-FACTOR 1A; INTRINSICALLY UNSTRUCTURED PROTEIN; ACID-STARVED CELLS; SACCHAROMYCES-CEREVISIAE; TRANSLATION ELONGATION; BUDDING YEAST; GI DOMAIN; ACTIVATION; INITIATION AB Yeast Yih1 protein and its mammalian ortholog IMPACT, abundant in neurons, are inhibitors of Gcn2, a kinase involved in amino acid homeostasis, stress response, and memory formation. Like Gcn2, Yih1/IMPACT harbors an N-terminal RWD domain that mediates binding to the Gcn2 activator Gcn1. Yih1 competes with Gcn2 for Gcn1 binding, thus inhibiting Gcn2. Yih1 also binds G-actin. Here, we show that Yih1-actin interaction is independent of Gcn1 and that Yih1-Gcn1 binding does not require actin. The Yih1 RWD (residues 1-132) was sufficient for Gcn2 inhibition and Gcn1 binding, but not for actin binding, showing that actin binding is dispensable for inhibiting Gcn2. Actin binding required Yih1 residues 68-258, encompassing part of the RWD and the C-terminal "ancient domain"; however, residues Asp-102 and Glu-106 in helix3 of the RWD were essential for Gcn1 binding and Gcn2 inhibition but dispensable for actin binding. Thus, the Gcn1- and actin-binding sites overlap in the RWD but have distinct binding determinants. Unexpectedly, Yih1 segment 68-258 was defective for inhibiting Gcn2 even though it binds Gcn1 at higher levels than does full-length Yih1. This and other results suggest that Yih1 binds with different requirements to distinct populations of Gcn1 molecules, and its ability to disrupt Gcn1-Gcn2 complexes is dependent on a complete RWD and hindered by actin binding. Modeling of the ancient domain on the bacterial protein YigZ showed peculiarities to the eukaryotic and prokaryotic lineages, suggesting binding sites for conserved cellular components. Our results support a role for Yih1 in a cross-talk between the cytoskeleton and translation. C1 [Sattlegger, Evelyn] Massey Univ, Inst Nat Sci, N Shore Mail Ctr, Auckland 0745, New Zealand. [Moraes, Maria Carolina S.; Martins, Rafael M.; Castilho, Beatriz A.] Univ Fed Sao Paulo, Dept Microbiol Imunol & Parasitol, BR-04023062 Sao Paulo, Brazil. [Sattlegger, Evelyn; Hinnebusch, Alan G.] NICHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. [Barbosa, Joao A. R. G.] Brazilian Synchrotron Light Lab, Ctr Struct Mol Biol, BR-13083970 Campinas, Brazil. RP Sattlegger, E (reprint author), Massey Univ, Inst Nat Sci, N Shore Mail Ctr, Private Bag 102 904, Auckland 0745, New Zealand. EM e.sattlegger@massey.ac.nz RI Castilho, Beatriz/C-2503-2012; Barbosa, Joao/E-2261-2012; OI Castilho, Beatriz/0000-0003-4509-5237; Barbosa, Joao/0000-0002-0534-481X; miyazawa martins, rafael/0000-0001-7449-0696 FU National Institutes of Health; Health Research Council of New Zealand; Auckland Medical Research Foundation; Massey University; Maurice and Phyllis Paykel Trust; Fundacao de Amparo a Pesquisa do Estado de Sao Paulo FX This work was supported, in whole or in part, by National Institutes of Health Intramural Research Program. This work was also supported in part by the Health Research Council of New Zealand Emerging Researcher First Grant, Auckland Medical Research Foundation, Massey University Research and Technician's Fund, Maurice and Phyllis Paykel Trust (to E. S.), and a grant from Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (to B. A. C.). NR 53 TC 13 Z9 16 U1 0 U2 11 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 25 PY 2011 VL 286 IS 12 BP 10341 EP 10355 DI 10.1074/jbc.M110.171587 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 737CU UT WOS:000288547000051 PM 21239490 ER PT J AU Figiel, M Chon, H Cerritelli, SM Cybulska, M Crouch, RJ Nowotny, M AF Figiel, Malgorzata Chon, Hyongi Cerritelli, Susana M. Cybulska, Magdalena Crouch, Robert J. Nowotny, Marcin TI The Structural and Biochemical Characterization of Human RNase H2 Complex Reveals the Molecular Basis for Substrate Recognition and Aicardi-Goutieres Syndrome Defects SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; DNA-REPLICATION; RIBONUCLEASE-H; HII; TYPE-2; MUTATIONS; MECHANISM; SUBUNITS; REMOVAL; HOMOLOG AB RNase H2 cleaves RNA sequences that are part of RNA/DNA hybrids or that are incorporated into DNA, thus, preventing genomic instability and the accumulation of aberrant nucleic acid, which in humans induces Aicardi-Goutieres syndrome, a severe autoimmune disorder. The 3.1 angstrom crystal structure of human RNase H2 presented here allowed us to map the positions of all 29 mutations found in Aicardi-Goutieres syndrome patients, several of which were not visible in the previously reported mouse RNase H2. We propose the possible effects of these mutations on the protein stability and function. Bacterial and eukaryotic RNases H2 differ in composition and substrate specificity. Bacterial RNases H2 are monomeric proteins and homologs of the eukaryotic RNases H2 catalytic subunit, which in addition possesses two accessory proteins. The eukaryotic RNase H2 heterotrimeric complex recognizes RNA/DNA hybrids and (5') RNA-DNA(3')/DNA junction hybrids as substrates with similar efficiency, whereas bacterial RNases H2 are highly specialized in the recognition of the (5') RNA-DNA(3') junction and very poorly cleave RNA/DNA hybrids in the presence of Mg(2+) ions. Using the crystal structure of the Thermotoga maritima RNase H2-substrate complex, we modeled the human RNase H2-substrate complex and verified the model by mutational analysis. Our model indicates that the difference in substrate preference stems from the different position of the crucial tyrosine residue involved in substrate binding and recognition. C1 [Figiel, Malgorzata; Cybulska, Magdalena; Nowotny, Marcin] Int Inst Mol & Cell Biol, Lab Prot Struct, PL-02109 Warsaw, Poland. [Chon, Hyongi; Cerritelli, Susana M.; Crouch, Robert J.] Eunice Kennedy Shriver NICHD, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA. RP Nowotny, M (reprint author), 4 Trojdena St, PL-02109 Warsaw, Poland. EM mnowotny@iimcb.gov.pl FU National Institutes of Health, Eunice Kennedy Shriver NICHD; Wellcome Trust [081760]; Polish Ministry of Science and Higher Education [ESRF/73/2006] FX work was supported, in whole or in part, by the National Institutes of Health Intramural Research Program of the Eunice Kennedy Shriver NICHD. This work was also supported by Wellcome Trust International Senior Fellowship 081760. The access to the European Synchrotron Radiation Facility was financed by the Polish Ministry of Science and Higher Education (Project ESRF/73/2006). NR 29 TC 23 Z9 26 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 25 PY 2011 VL 286 IS 12 BP 10540 EP 10550 DI 10.1074/jbc.M110.181974 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 737CU UT WOS:000288547000070 PM 21177858 ER PT J AU Fumagalli, M Daniele, S Lecca, D Lee, PR Parravicini, C Fields, RD Rosa, P Antonucci, F Verderio, C Trincavelli, ML Bramanti, P Martini, C Abbracchio, MP AF Fumagalli, Marta Daniele, Simona Lecca, Davide Lee, Philip R. Parravicini, Chiara Fields, R. Douglas Rosa, Patrizia Antonucci, Flavia Verderio, Claudia Trincavelli, M. Letizia Bramanti, Placido Martini, Claudia Abbracchio, Maria P. TI Phenotypic Changes, Signaling Pathway, and Functional Correlates of GPR17-expressing Neural Precursor Cells during Oligodendrocyte Differentiation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID P2Y-LIKE RECEPTOR GPR17; ADENOSINE; MYELINATION; EXPRESSION; RAT; DESENSITIZATION; DERIVATIVES; ANTAGONISTS; ASTROCYTES; CULTURES AB The developing and mature central nervous system contains neural precursor cells expressing the proteoglycan NG2. Some of these cells continuously differentiate to myelin-forming oligodendrocytes; knowledge of the destiny of NG2(+) precursors would benefit from the characterization of new key functional players. In this respect, the G protein-coupled membrane receptor GPR17 has recently emerged as a new timer of oligodendrogliogenesis. Here, we used purified oligodendrocyte precursor cells (OPCs) to fully define the immunophenotype of the GPR17-expressing cells during OPC differentiation, unveil its native signaling pathway, and assess the functional consequences of GPR17 activation by its putative endogenous ligands, uracil nucleotides and cysteinyl leukotrienes (cysLTs). GPR17 presence was restricted to very early differentiation stages and completely segregated from that of mature myelin. Specifically, GPR17 decorated two subsets of slowly proliferating NG2(+) OPCs: (i) morphologically immature cells expressing other early proteins like Olig2 and PDGF receptor-alpha, and (ii) ramified preoligodendrocytes already expressing more mature factors, like O4 and O1. Thus, GPR17 is a new marker of these transition stages. In OPCs, GPR17 activation by either uracil nucleotides or cysLTs resulted in potent inhibition of intracellular cAMP formation. This effect was counteracted by GPR17 antagonists and receptor silencing with siRNAs. Finally, uracil nucleotides promoted and GPR17 inhibition, by either antagonists or siRNAs, impaired the normal program of OPC differentiation. These data have implications for the in vivo behavior of NG2(+) OPCs and point to uracil nucleotides and cysLTs as main extrinsic local regulators of these cells under physiological conditions and during myelin repair. C1 [Fumagalli, Marta; Lecca, Davide; Parravicini, Chiara; Abbracchio, Maria P.] Univ Milan, Dept Pharmacol Sci, Lab Mol & Cellular Pharmacol Purinerg Transmiss, I-20133 Milan, Italy. [Daniele, Simona; Trincavelli, M. Letizia; Martini, Claudia] Univ Pisa, Dept Psychiat Neurobiol Pharmacol & Biotechnol, I-56126 Pisa, Italy. [Lee, Philip R.; Fields, R. Douglas] NIH, Nervous Syst Dev & Plast Sect, Bethesda, MD 20817 USA. [Rosa, Patrizia; Antonucci, Flavia; Verderio, Claudia] CNR, Dept Med Pharmacol, Inst Neurosci, I-20129 Milan, Italy. [Bramanti, Placido] Ctr Neurolesi Bonino Pulejo, I-98121 Messina, Italy. RP Abbracchio, MP (reprint author), Univ Milan, Dept Pharmacol Sci, Lab Mol & Cellular Pharmacol Purinerg Transmiss, Via Balzaretti 9, I-20133 Milan, Italy. EM mariapia.abbracchio@unimi.it RI Lecca, Davide/A-8850-2010; Abbracchio, Maria Pia/B-9342-2014; Verderio, Claudia/K-4415-2016; OI Lecca, Davide/0000-0002-3258-363X; Abbracchio, Maria Pia/0000-0002-7833-3388; Verderio, Claudia/0000-0001-7216-5873; Fumagalli, Marta/0000-0002-0158-842X; Trincavelli, Maria Letizia/0000-0001-8124-977X; Martini, Claudia/0000-0001-9379-3027 FU NICHD, National Institutes of Health; Italian Ministero della Salute [RF-CNM-2007-662855]; PRIN-COFIN Project [2006059022, 2008XFMEA3]; FISM, Fondazione Italiana Sclerosi Multipla [COD. 2010/R/2] FX This work was supported by the Intramural Research Program of the NICHD, National Institutes of Health. This work was also supported by Italian Ministero della Salute RF-CNM-2007-662855 and PRIN-COFIN Project Prot. 2006059022 and 2008XFMEA3 and by FISM, Fondazione Italiana Sclerosi Multipla COD. 2010/R/2. NR 29 TC 60 Z9 65 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 25 PY 2011 VL 286 IS 12 BP 10593 EP 10604 DI 10.1074/jbc.M110.162867 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 737CU UT WOS:000288547000074 PM 21209081 ER PT J AU Zhang, K Fischer, T Porter, RL Dhakshnamoorthy, J Zofall, M Zhou, M Veenstra, T Grewal, SIS AF Zhang, Ke Fischer, Tamas Porter, Rebecca L. Dhakshnamoorthy, Jothy Zofall, Martin Zhou, Ming Veenstra, Timothy Grewal, Shiv I. S. TI Clr4/Suv39 and RNA Quality Control Factors Cooperate to Trigger RNAi and Suppress Antisense RNA SO SCIENCE LA English DT Article ID FISSION YEAST; CHROMOSOME SEGREGATION; LYSINE METHYLATION; MRNP FORMATION; HETEROCHROMATIN; COMPLEX; EXPORT; TRANSCRIPTION; PROTEINS; DEGRADATION AB Pervasive transcription of eukaryotic genomes generates a plethora of noncoding RNAs. In fission yeast, the heterochromatin factor Clr4/Suv39 methyltransferase facilitates RNA interference (RNAi)-mediated processing of centromeric transcripts into small interfering RNAs (siRNAs). Clr4 also mediates degradation of antisense RNAs at euchromatic loci, but the underlying mechanism has remained elusive. We show that Clr4 and the RNAi effector RITS (RNA-induced transcriptional silencing) interact with Mlo3, a protein related to mRNA quality control and export factors. Loss of Clr4 impairs RITS interaction with Mlo3, which is required for centromeric siRNA production and antisense suppression. Mlo3 also interacts with the RNA surveillance factor TRAMP, which suppresses antisense RNAs targeted by Clr4 and RNAi. These findings link Clr4 to RNA quality control machinery and suggest a pathway for processing potentially deleterious RNAs through the coordinated actions of RNAi and other RNA processing activities. C1 [Zhang, Ke; Fischer, Tamas; Porter, Rebecca L.; Dhakshnamoorthy, Jothy; Zofall, Martin; Grewal, Shiv I. S.] NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Zhou, Ming; Veenstra, Timothy] NCI, Lab Prote & Analyt Anal, Frederick, MD 21702 USA. RP Grewal, SIS (reprint author), NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM grewals@mail.nih.gov RI Fischer, Tamas/A-7729-2016 OI Fischer, Tamas/0000-0002-7996-4042 FU National Institutes of Health, National Cancer Institute FX We thank R. Dhar and R. Allshire for antibody to Mlo3 and strains, E. Chen for helpful contributions, and F. Reyes-Turcu, N. Komissarova, and M. Lichten for comments on manuscripts and discussions. Microarray data are available at the National Center for Biotechnology Information's Gene Expression Omnibus repository under accession numbers GSE26999 and GSE17271. This work is supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. NR 27 TC 39 Z9 39 U1 2 U2 10 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAR 25 PY 2011 VL 331 IS 6024 BP 1624 EP 1627 DI 10.1126/science.1198712 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 739XH UT WOS:000288754500061 PM 21436456 ER PT J AU Bennett, RS Gresko, AK Murphy, BR Whitehead, SS AF Bennett, Richard S. Gresko, Anthony K. Murphy, Brian R. Whitehead, Stephen S. TI Tahyna virus genetics, infectivity, and immunogenicity in mice and monkeys SO VIROLOGY JOURNAL LA English DT Article ID CALIFORNIA SEROGROUP BUNYAVIRUSES; NONSTRUCTURAL PROTEIN NSS; LA-CROSSE; SEQUENCE; GENOME; PATHOGENESIS; SEGMENT; LUMBO AB Background: Tahyna virus (TAHV) is a human pathogen of the California encephalitis virus (CEV) serogroup (Bunyaviridae) endemic to Europe, Asia, and Africa. TAHV maintains an enzootic life cycle with several species of mosquito vectors and hares, rabbits, hedgehogs, and rodents serving as small mammal amplifying hosts. Human TAHV infection occurs in summer and early fall with symptoms of fever, headache, malaise, conjunctivitis, pharyngitis, and nausea. TAHV disease can progress to CNS involvement, although unlike related La Crosse virus (LACV), fatalities have not been reported. Human infections are frequent with neutralizing antibodies present in 60-80% of the elderly population in endemic areas. Results: In order to determine the genomic sequence of wild-type TAHV, we chose three TAHV isolates collected over a 26-year period from mosquitoes. Here we present the first complete sequence of the TAHV S, M, and L segments. The three TAHV isolates maintained a highly conserved genome with both nucleotide and amino acid sequence identity greater than 99%. In order to determine the extent of genetic relatedness to other members of the CEV serogroup, we compared protein sequences of TAHV with LACV, Snowshoe Hare virus (SSHV), Jamestown Canyon virus (JCV), and Inkoo virus (INKV). By amino acid comparison, TAHV was most similar to SSHV followed by LACV, JCV, and INKV. The sequence of the GN protein is most conserved followed by L, N, GC, NSS, and NSM. In a weanling Swiss Webster mouse model, all three TAHV isolates were uniformly neurovirulent, but only one virus was neuroinvasive. In rhesus monkeys, the virus was highly immunogenic even in the absence of viremia. Cross neutralization studies utilizing monkey immune serum demonstrated that TAHV is antigenically distinct from North American viruses LACV and JCV. Conclusions: Here we report the first complete sequence of TAHV and present genetic analysis of new-world viruses, LACV, SSHV, and JCV with old-world viruses, TAHV and INKV. Using immune serum generated in monkeys against TAHV, LACV, and JCV, we have demonstrated cross-neutralization within the CEV serogroup. Such cross reactivity may complicate virus identification, especially following JCV infection which elicited antibodies that cross neutralized both LACV and TAHV. These data also suggest that a single vaccine could generate a cross-neutralizing antibody response which may provide protection against CEV serogroup viruses from a wide geographic range. C1 [Bennett, Richard S.; Gresko, Anthony K.; Murphy, Brian R.; Whitehead, Stephen S.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Whitehead, SS (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. EM swhitehead@niaid.nih.gov OI Bennett, Richard/0000-0002-7227-4831 FU NIAID Division of Intramural Research in Bethesda, MD FX The authors wish to thank Dr. Robert Tesh for providing the TAHV isolates used in this study. This work was supported with funds from the NIAID Division of Intramural Research in Bethesda, MD. NR 27 TC 6 Z9 7 U1 1 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1743-422X J9 VIROL J JI Virol. J. PD MAR 24 PY 2011 VL 8 AR 135 DI 10.1186/1743-422X-8-135 PG 14 WC Virology SC Virology GA 754GD UT WOS:000289842100001 PM 21435229 ER PT J AU McKenna, DJ Ruiz, JM Hoye, TR Roth, BL Shoemaker, AT AF McKenna, Dennis J. Ruiz, Juan M. Hoye, Thomas R. Roth, Bryan L. Shoemaker, Alan T. TI Receptor screening technologies in the evaluation of Amazonian ethnomedicines with potential applications to cognitive deficits SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Schizophrenia; Cognitive disorders; Dementia; Mental disorders; Ethnomedicine; Rodioligand assay; Ethnopharmacology; Drug prospecting ID ALZHEIMERS-DISEASE; DRUG DEVELOPMENT; BINDING ASSAYS; ANTIPSYCHOTIC-DRUGS; SEROTONIN RECEPTORS; MOLECULAR TARGETS; NEGATIVE SYMPTOMS; MEDICINAL-PLANTS; NATURAL-PRODUCTS; SALVINORIN-A AB Ethnopharmacological relevance: Amazonian peoples utilize a variety of psychoactive plants that may contain novel biologically active compounds. Efforts to investigate such remedies in terms of neuropharmacology have been limited. Aim of this study: This study identified Amazonian ethnomedicines with potential for the treatment of cognitive deficits in schizophrenia and dementias, and characterized their interactions with CNS neurotransmitter receptors in vitro. Materials and methods: Approximately 300 Amazonian species with folk uses or constituents indicative of central nervous system activity were incorporated into a database constructed from literature searches, herbarium surveys, and interviews with traditional practitioners. Approximately 130 of these targeted species were collected in Loreto province, Peru, and 228 fractions derived from them were screened in 31 radioreceptor assays via the resources of the NIMH Psychoactive Drug Screening Program. A subset was also screened in functional assays at selected serotonin, muscarinic, and adrenergic receptors. Results: Ninety-one samples displayed >= 60% inhibition of radioligand binding activity in receptor assays; 135 samples displayed agonist or antagonist activity (or both) in functional assays. Conclusions: Potential CNS activity was detected in about 40% of the samples screened, with some correlations to both folk uses and phytochemical constituents. These results may point to novel and potentially therapeutic CNS active compounds. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [McKenna, Dennis J.] Univ Minnesota, Acad Hlth Ctr, Ctr Spiritual & Healing, Minneapolis, MN 55455 USA. [Ruiz, Juan M.] UNAP, Fac Ciencias Biol, Herbarium Amazonense, Iquitos, Peru. [Hoye, Thomas R.] Univ Minnesota, Dept Chem, Minneapolis, MN 55455 USA. [Roth, Bryan L.] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA. [Roth, Bryan L.] NIMH Psychoact Drug Screeing Program, Chapel Hill, NC 27599 USA. [Shoemaker, Alan T.] Gracia Ethnobot, Iquitos, Peru. RP McKenna, DJ (reprint author), Univ Minnesota, Acad Hlth Ctr, Ctr Spiritual & Healing, MMC505,420 Delaware St SE, Minneapolis, MN 55455 USA. EM mcken031@umn.edu RI Roth, Bryan/F-3928-2010 FU Stanley Medical Research Institute [04T-505]; NIMH [NO1MH32004] FX This work was supported under Grant # 04T-505 from the Stanley Medical Research Institute and the NIMH Psychoactive Drug Screening Program, Contract # NO1MH32004 (NIMH PDSP). NR 82 TC 5 Z9 6 U1 0 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-8741 J9 J ETHNOPHARMACOL JI J. Ethnopharmacol. PD MAR 24 PY 2011 VL 134 IS 2 BP 475 EP 492 DI 10.1016/j.jep.2010.12.037 PG 18 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 747OO UT WOS:000289329500039 PM 21232588 ER PT J AU Bennett, RS Nelson, JT Gresko, AK Murphy, BR Whitehead, SS AF Bennett, Richard S. Nelson, Jacob T. Gresko, Anthony K. Murphy, Brian R. Whitehead, Stephen S. TI The full genome sequence of three strains of Jamestown Canyon virus and their pathogenesis in mice or monkeys SO VIROLOGY JOURNAL LA English DT Article ID CALIFORNIA SEROGROUP BUNYAVIRUSES; ENCEPHALITIS-VIRUS; POPULATIONS; INFECTIONS; SEROEPIDEMIOLOGY; CONNECTICUT; MICHIGAN; ANTIBODY; HUMANS; CANADA AB Background: Jamestown Canyon virus (JCV), family Bunyaviridae, is a mosquito-borne pathogen endemic in the United States and Canada that can cause encephalitis in humans and is considered an emerging threat to public health. The virus is genetically similar to Inkoo virus circulating in Europe, suggesting that much of the northern hemisphere contains JCV or similar variants. Results: We have completed the sequence of three isolates of JCV collected in geographically diverse locations over a 57 year time span. The nucleotide identity for the three strains is 90, 83, and 85% for the S, M, and L segments respectively whereas the percent identify for the predicted amino acid sequences of the N, NSS, M poly, G(N), NSM, G(C), and L proteins was 97, 91, 94, 98, 91, 94, and 97%, respectively. In Swiss Webster mice, each JCV isolate exhibits low neuroinvasiveness but high infectivity. Two of the three JCV isolates were highly neurovirulent after IC inoculation whereas one isolate, JCV/03/CT, exhibited low neurovirulence. In rhesus monkeys, JCV infection is accompanied by a low-titered viremia, lack of clinical disease, but a robust neutralizing antibody response. Conclusions: The first complete sequence of JCV is reported for three separate isolates, and a relatively high level of amino acid sequence conservation was observed even for viruses isolated 57 years apart indicating that the virus is in relative evolutionary stasis. JCV is highly infectious for mice and monkeys, and these animals, especially mice, represent useful experimental hosts for further study. C1 [Bennett, Richard S.; Nelson, Jacob T.; Gresko, Anthony K.; Murphy, Brian R.; Whitehead, Stephen S.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Whitehead, SS (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. EM swhitehead@niaid.nih.gov OI Bennett, Richard/0000-0002-7227-4831 FU NIAID Division of Intramural Research, National Institutes of Health in Bethesda, MD FX The authors wish to thank Bob Tesh for the JCV/61/CO virus stock. We would also like to thank Philip Armstrong and Theodore Andreadis for providing JCV/03/CT and JCV/04/CT stocks. We acknowledge Brad Finneyfrock, and the staff of Bioqual, Inc for their assistance in conducting the studies with rhesus monkeys. This work was supported with funds from the NIAID Division of Intramural Research, National Institutes of Health in Bethesda, MD. NR 25 TC 1 Z9 1 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1743-422X J9 VIROL J JI Virol. J. PD MAR 24 PY 2011 VL 8 AR 136 DI 10.1186/1743-422X-8-136 PG 11 WC Virology SC Virology GA 749QU UT WOS:000289484700001 PM 21435230 ER PT J AU Nishiura, H Chowell, G Castillo-Chavez, C AF Nishiura, Hiroshi Chowell, Gerardo Castillo-Chavez, Carlos TI Did Modeling Overestimate the Transmission Potential of Pandemic (H1N1-2009)? Sample Size Estimation for Post-Epidemic Seroepidemiological Studies SO PLOS ONE LA English DT Article ID H1N1 INFLUENZA-VIRUS; FINAL-SIZE; INFECTIOUS-DISEASE; STOCHASTIC EPIDEMIC; INTERVAL ESTIMATION; REAL-TIME; INFERENCE; PREVALENCE; ANTIBODIES; SEVERITY AB Background: Seroepidemiological studies before and after the epidemic wave of H1N1-2009 are useful for estimating population attack rates with a potential to validate early estimates of the reproduction number, R, in modeling studies. Methodology/Principal Findings: Since the final epidemic size, the proportion of individuals in a population who become infected during an epidemic, is not the result of a binomial sampling process because infection events are not independent of each other, we propose the use of an asymptotic distribution of the final size to compute approximate 95% confidence intervals of the observed final size. This allows the comparison of the observed final sizes against predictions based on the modeling study (R = 1.15, 1.40 and 1.90), which also yields simple formulae for determining sample sizes for future seroepidemiological studies. We examine a total of eleven published seroepidemiological studies of H1N1-2009 that took place after observing the peak incidence in a number of countries. Observed seropositive proportions in six studies appear to be smaller than that predicted from R = 1.40; four of the six studies sampled serum less than one month after the reported peak incidence. The comparison of the observed final sizes against R = 1.15 and 1.90 reveals that all eleven studies appear not to be significantly deviating from the prediction with R = 1.15, but final sizes in nine studies indicate overestimation if the value R = 1.90 is used. Conclusions: Sample sizes of published seroepidemiological studies were too small to assess the validity of model predictions except when R = 1.90 was used. We recommend the use of the proposed approach in determining the sample size of post-epidemic seroepidemiological studies, calculating the 95% confidence interval of observed final size, and conducting relevant hypothesis testing instead of the use of methods that rely on a binomial proportion. C1 [Nishiura, Hiroshi] PRESTO, Japan Sci & Technol Agcy, Saitama, Japan. [Nishiura, Hiroshi] Univ Utrecht, Utrecht, Netherlands. [Nishiura, Hiroshi] Univ Hong Kong, Sch Publ Hlth, Hong Kong, Hong Kong, Peoples R China. [Chowell, Gerardo; Castillo-Chavez, Carlos] Arizona State Univ, Math & Computat Modeling Sci Ctr, Sch Human Evolut & Social Change, Tempe, AZ USA. [Chowell, Gerardo] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Castillo-Chavez, Carlos] Santa Fe Inst, Santa Fe, NM 87501 USA. RP Nishiura, H (reprint author), PRESTO, Japan Sci & Technol Agcy, Saitama, Japan. EM nishiura@hku.hk RI Nishiura, Hiroshi/D-1426-2011; Chowell, Gerardo/F-5038-2012; Castillo-Chavez, Carlos/E-1412-2014; OI Chowell, Gerardo/0000-0003-2194-2251; Castillo-Chavez, Carlos/0000-0002-1046-3901; Nishiura, Hiroshi/0000-0003-0941-8537 FU Japan Science and Technology Agency PRESTO; College of the Liberal Arts and Sciences of Arizona State University; National Science Foundation (NSF) [DMS - 0502349]; U.S. Department of Defense (NSA) [H98230-06-1-0097]; Alfred T. Sloan Foundation; Office of the Provost of Arizona State University FX HN was supported by the Japan Science and Technology Agency PRESTO program. GC received financial support from the College of the Liberal Arts and Sciences of Arizona State University. National Science Foundation (NSF - Grant DMS - 0502349), U.S. Department of Defense (NSA - Grant H98230-06-1-0097), the Alfred T. Sloan Foundation and the Office of the Provost of Arizona State University support CCC's research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 65 TC 18 Z9 18 U1 3 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 MAR 24 PY 2011 VL 6 IS 3 AR e17908 DI 10.1371/journal.pone.0017908 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 740RG UT WOS:000288811500015 PM 21455307 ER PT J AU Spencer, KL Olson, LM Schnetz-Boutaud, N Gallins, P Agarwal, A Iannaccone, A Kritchevsky, SB Garcia, M Nalls, MA Newman, AB Scott, WK Pericak-Vance, MA Haines, JL AF Spencer, Kylee L. Olson, Lana M. Schnetz-Boutaud, Nathalie Gallins, Paul Agarwal, Anita Iannaccone, Alessandro Kritchevsky, Stephen B. Garcia, Melissa Nalls, Michael A. Newman, Anne B. Scott, William K. Pericak-Vance, Margaret A. Haines, Jonathan L. TI Using Genetic Variation and Environmental Risk Factor Data to Identify Individuals at High Risk for Age-Related Macular Degeneration SO PLOS ONE LA English DT Article ID COMPLEMENT FACTOR-H; PIGMENT OPTICAL-DENSITY; BREAST-CANCER; UNITED-STATES; FACTOR-B; ASSOCIATION; POLYMORPHISM; DISEASE; VARIANT; SUSCEPTIBILITY AB A major goal of personalized medicine is to pre-symptomatically identify individuals at high risk for disease using knowledge of each individual's particular genetic profile and constellation of environmental risk factors. With the identification of several well-replicated risk factors for age-related macular degeneration (AMD), the leading cause of legal blindness in older adults, this previously unreachable goal is beginning to seem less elusive. However, recently developed algorithms have either been much less accurate than expected, given the strong effects of the identified risk factors, or have not been applied to independent datasets, leaving unknown how well they would perform in the population at large. We sought to increase accuracy by using novel modeling strategies, including multifactor dimensionality reduction (MDR) and grammatical evolution of neural networks (GENN), in addition to the traditional logistic regression approach. Furthermore, we rigorously designed and tested our models in three distinct datasets: a Vanderbilt-Miami (VM) clinic-based case-control dataset, a VM family dataset, and the population-based Age-related Maculopathy Ancillary (ARMA) Study cohort. Using a consensus approach to combine the results from logistic regression and GENN models, our algorithm was successful in differentiating between high- and low-risk groups (sensitivity 77.0%, specificity 74.1%). In the ARMA cohort, the positive and negative predictive values were 63.3% and 70.7%, respectively. We expect that future efforts to refine this algorithm by increasing the sample size available for model building, including novel susceptibility factors as they are discovered, and by calibrating the model for diverse populations will improve accuracy. C1 [Spencer, Kylee L.; Olson, Lana M.; Schnetz-Boutaud, Nathalie; Haines, Jonathan L.] Vanderbilt Univ, Ctr Human Genet Res, Nashville, TN 37235 USA. [Gallins, Paul; Scott, William K.; Pericak-Vance, Margaret A.] Univ Miami, Miller Sch Med, John P Hussman Inst Human Genom, Miami, FL 33136 USA. [Agarwal, Anita] Vanderbilt Univ, Med Ctr, Vanderbilt Eye Inst, Nashville, TN USA. [Iannaccone, Alessandro] Univ Tennessee, Hlth Sci Ctr, Hamilton Eye Inst, Memphis, TN USA. [Kritchevsky, Stephen B.] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN USA. [Kritchevsky, Stephen B.] Wake Forest Univ, Sticht Ctr Aging, Winston Salem, NC 27109 USA. [Garcia, Melissa] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Nalls, Michael A.] NIA, Neurogenet Lab, Bethesda, MD 20892 USA. [Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. RP Spencer, KL (reprint author), Vanderbilt Univ, Ctr Human Genet Res, Nashville, TN 37235 USA. EM Kylee.Spencer@vanderbilt.edu RI Haines, Jonathan/C-3374-2012; Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Kritchevsky, Stephen/0000-0003-3336-6781 FU National Institutes of Health (NIH)/National Eye Institute [EY12118, EY000409]; NIH/National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; International Retinal Research Foundation, Inc., Birmingham, AL; Research to Prevent Blindness, New York, NY; NIH/NIA FX This work was supported by grants EY12118 (to M.A.P.-V. and J.L.H.) and EY000409 (K23 Award to A.I.) from the National Institutes of Health (NIH)/National Eye Institute, contracts N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106 (to S.B.K.) from the NIH/National Institute on Aging (NIA), grants from the International Retinal Research Foundation, Inc., Birmingham, AL (to A.I.), by Research to Prevent Blindness, New York, NY (Career Development Award to A.I. and an unrestricted grant to the UTHSC Hamilton Eye Institute), and in part by the Intramural Research Program of the NIH/NIA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 38 TC 24 Z9 24 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 24 PY 2011 VL 6 IS 3 AR e17784 DI 10.1371/journal.pone.0017784 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 740RG UT WOS:000288811500009 PM 21455292 ER PT J AU Graveley, BR Brooks, AN Carlson, J Duff, MO Landolin, JM Yang, L Artieri, CG van Baren, MJ Boley, N Booth, BW Brown, JB Cherbas, L Davis, CA Dobin, A Li, RH Lin, W Malone, JH Mattiuzzo, NR Miller, D Sturgill, D Tuch, BB Zaleski, C Zhang, DY Blanchette, M Dudoit, S Eads, B Green, RE Hammonds, A Jiang, LC Kapranov, P Langton, L Perrimon, N Sandler, JE Wan, KH Willingham, A Zhang, Y Zou, Y Andrews, J Bickel, PJ Brenner, SE Brent, MR Cherbas, P Gingeras, TR Hoskins, RA Kaufman, TC Oliver, B Celniker, SE AF Graveley, Brenton R. Brooks, Angela N. Carlson, JosephW. Duff, Michael O. Landolin, Jane M. Yang, Li Artieri, Carlo G. van Baren, Marijke J. Boley, Nathan Booth, Benjamin W. Brown, James B. Cherbas, Lucy Davis, Carrie A. Dobin, Alex Li, Renhua Lin, Wei Malone, John H. Mattiuzzo, Nicolas R. Miller, David Sturgill, David Tuch, Brian B. Zaleski, Chris Zhang, Dayu Blanchette, Marco Dudoit, Sandrine Eads, Brian Green, Richard E. Hammonds, Ann Jiang, Lichun Kapranov, Phil Langton, Laura Perrimon, Norbert Sandler, Jeremy E. Wan, Kenneth H. Willingham, Aarron Zhang, Yu Zou, Yi Andrews, Justen Bickel, Peter J. Brenner, Steven E. Brent, Michael R. Cherbas, Peter Gingeras, Thomas R. Hoskins, Roger A. Kaufman, Thomas C. Oliver, Brian Celniker, Susan E. TI The developmental transcriptome of Drosophila melanogaster SO NATURE LA English DT Article ID BITHORAX COMPLEX; GENE-EXPRESSION; COMPARATIVE GENOMICS; FUNCTIONAL ELEMENTS; LARVAL DEVELOPMENT; ABDOMINAL-B; IDENTIFICATION; TARGETS; SYSTEM; DOMAIN AB Drosophila melanogaster is one of the most well studied genetic model organisms; nonetheless, its genome still contains unannotated coding and non-coding genes, transcripts, exons and RNA editing sites. Full discovery and annotation are pre-requisites for understanding how the regulation of transcription, splicing and RNA editing directs the development of this complex organism. Here we used RNA-Seq, tiling microarrays and cDNA sequencing to explore the transcriptome in 30 distinct developmental stages. We identified 111,195 new elements, including thousands of genes, coding and non-coding transcripts, exons, splicing and editing events, and inferred protein isoforms that previously eluded discovery using established experimental, prediction and conservation-based approaches. These data substantially expand the number of known transcribed elements in the Drosophila genome and provide a high-resolution view of transcriptome dynamics throughout development. C1 [Graveley, Brenton R.; Duff, Michael O.; Yang, Li] Univ Connecticut, Ctr Hlth, Dept Genet & Dev Biol, Farmington, CT 06030 USA. [Brooks, Angela N.; Brenner, Steven E.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. [Carlson, JosephW.; Landolin, Jane M.; Booth, Benjamin W.; Hammonds, Ann; Sandler, Jeremy E.; Wan, Kenneth H.; Hoskins, Roger A.; Celniker, Susan E.] Univ Calif Berkeley, Lawrence Berkeley Lab, Dept Genome Dynam, Berkeley, CA 94720 USA. [Artieri, Carlo G.; Li, Renhua; Malone, John H.; Mattiuzzo, Nicolas R.; Sturgill, David; Jiang, Lichun; Zhang, Yu; Oliver, Brian] NIDDK, Sect Dev Genom, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA. [van Baren, Marijke J.; Langton, Laura; Brent, Michael R.] Washington Univ, Ctr Genome Sci, St Louis, MO 63108 USA. [van Baren, Marijke J.; Langton, Laura; Brent, Michael R.] Washington Univ, Dept Comp Sci, St Louis, MO 63108 USA. [Boley, Nathan; Brown, James B.; Bickel, Peter J.] Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA. [Cherbas, Lucy; Zhang, Dayu; Cherbas, Peter] Indiana Univ, Ctr Genom & Bioinformat, Bloomington, IN 47405 USA. [Davis, Carrie A.; Dobin, Alex; Lin, Wei; Zaleski, Chris; Kapranov, Phil; Gingeras, Thomas R.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. [Miller, David; Eads, Brian; Andrews, Justen; Cherbas, Peter; Kaufman, Thomas C.] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA. [Tuch, Brian B.] Life Technol, Res & Dev, Genet Syst Div, Foster City, CA 94404 USA. [Tuch, Brian B.] Amgen Inc, Genome Anal Unit, San Francisco, CA 94080 USA. [Blanchette, Marco] Stowers Inst Med Res, Kansas City, MO 64110 USA. [Blanchette, Marco] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66160 USA. [Dudoit, Sandrine] Univ Calif Berkeley, Sch Publ Hlth, Div Biostat, Berkeley, CA 94720 USA. [Green, Richard E.] Univ Calif Santa Cruz, Dept Biomol Engn, Santa Cruz, CA 95064 USA. [Perrimon, Norbert] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Perrimon, Norbert] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. [Willingham, Aarron; Brenner, Steven E.] Univ Calif Berkeley, Dept Plant & Microbial Biol, Berkeley, CA 94720 USA. [Gingeras, Thomas R.] Affymetrix, Santa Clara, CA 95051 USA. RP Graveley, BR (reprint author), Univ Connecticut, Ctr Hlth, Dept Genet & Dev Biol, 263 Farmington Ave, Farmington, CT 06030 USA. EM graveley@neuron.uchc.edu; celniker@fruitfly.org RI jiang, lichun/F-3776-2012; Graveley, Brenton/C-3108-2013; Brown, James/H-2971-2015; Brenner, Steven/A-8729-2008; OI jiang, lichun/0000-0003-2462-7636; Brenner, Steven/0000-0001-7559-6185; Gingeras, Thomas/0000-0001-9106-3573; Graveley, Brenton/0000-0001-5777-5892 FU National Human Genome Research INstitute [U01 HB004271]; Department of Energy [DE-AC02-05CH11231]; National Institute of Diabetes and Digestive and Kidney Diseases FX We thank C. Trapnell and L. Pachter for discussions and assistance with Cufflinks, and E. Clough for comments and feedback. A.N.B. was partially supported by an NSF graduate fellowship. This work was funded by an award from the National Human Genome Research INstitute modENCODE Project (U01 HB004271) to S.E.C. (Principal Investigator) and M.R.B., P.C., T.R.G., B.R.G. and N.P. (co-Principal Investigators) under Department of Energy contract no. DE-AC02-05CH11231, and by the National Institute of Diabetes and Digestive and Kidney Diseases Intramural Research Program (B.O.). NR 49 TC 566 Z9 582 U1 23 U2 168 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 24 PY 2011 VL 471 IS 7339 BP 473 EP 479 DI 10.1038/nature09715 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 739GJ UT WOS:000288702200054 PM 21179090 ER PT J AU Karp, JE Smith, BD Resar, LS Greer, JM Blackford, A Zhao, M Moton-Nelson, D Alino, K Levis, MJ Gore, SD Joseph, B Carraway, H McDevitt, MA Bagain, L Mackey, K Briel, J Doyle, LA Wright, JJ Rudek, MA AF Karp, Judith E. Smith, B. Douglas Resar, Linda S. Greer, Jacqueline M. Blackford, Amanda Zhao, Ming Moton-Nelson, Dwella Alino, Katrina Levis, Mark J. Gore, Steven D. Joseph, Biju Carraway, Hetty McDevitt, Michael A. Bagain, Lorena Mackey, Karen Briel, Janet Doyle, L. Austin Wright, John J. Rudek, Michelle A. TI Phase 1 and pharmacokinetic study of bolus-infusion flavopiridol followed by cytosine arabinoside and mitoxantrone for acute leukemias SO BLOOD LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; REFRACTORY ACUTE LEUKEMIAS; 72-HOUR CONTINUOUS-INFUSION; BREAST-CARCINOMA CELLS; ACUTE MYELOID-LEUKEMIA; TRANSCRIPTIONAL REPRESSION; CYTOTOXIC SYNERGY; CLINICAL ACTIVITY; GENE-EXPRESSION; DOWN-REGULATION AB Flavopiridol is a protein bound, cytotoxic, cyclin-dependent kinase inhibitor. Flavopiridol given by 1-hour bolus at 50 mg/m(2) daily 3 times followed by cytosine arabinoside and mitoxantrone (FLAM) is active in adults with poor-risk acute leukemias. A pharmacologically derived "hybrid" schedule (30-minute bolus followed by 4-hour infusion) of flavopiridol was more effective than bolus administration in refractory chronic lymphocytic leukemia. Our phase 1 trial "hybrid FLAM" in 55 adults with relapsed/refractory acute leukemias began at a total flavopiridol dose of 50 mg/m(2) per day 3 times (20-mg/m(2) bolus, 30-mg/m(2) infusion). Dose-limiting toxicity occurred at level 6 (30-mg/m(2) bolus, 70-mg/m(2) infusion) with tumor lysis, hyperbilirubinemia, and mucositis. Death occurred in 5 patients (9%). Complete remission occurred in 22 (40%) across all doses. Overall and disease-free survivals for complete remission patients are more than 60% at more than 2 years. Pharmacokinetics demonstrated a dose-response for total and unbound plasma flavopiridol unrelated to total protein, albumin, peripheral blast count, or toxicity. Pharmacodynamically, flavopiridol inhibited mRNAs of multiple cell cycle regulators, but with uniform increases in bcl-2. "Hybrid FLAM" is active in relapsed/refractory acute leukemias, with a recommended "hybrid" dose of bolus 30 mg/m(2) followed by infusion of 60 mg/m(2) daily for 3 days. This clinical trial is registered at www.clinicaltrials.gov as #NCT00470197. (Blood. 2011;117(12):3302-3310) C1 [Karp, Judith E.; Smith, B. Douglas; Greer, Jacqueline M.; Blackford, Amanda; Alino, Katrina; Levis, Mark J.; Gore, Steven D.; Carraway, Hetty; McDevitt, Michael A.; Mackey, Karen; Briel, Janet] Johns Hopkins Sidney Kimmel Comprehens Canc Ctr, Div Hematol Malignancies, Baltimore, MD 21231 USA. [Resar, Linda S.; Moton-Nelson, Dwella; Joseph, Biju; McDevitt, Michael A.] Johns Hopkins Med Inst, Dept Med, Div Hematol, Baltimore, MD 21205 USA. [Zhao, Ming; Bagain, Lorena; Rudek, Michelle A.] Johns Hopkins Sidney Kimmel Comprehens Canc Ctr, Div Chem Therapeut, Baltimore, MD 21231 USA. [Doyle, L. Austin; Wright, John J.] NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Karp, JE (reprint author), Johns Hopkins Sidney Kimmel Comprehens Canc Ctr, Div Hematol Malignancies, 1650 Orleans St,CRB 1,Rm 2M44, Baltimore, MD 21231 USA. EM jkarp2@jhmi.edu FU National Institutes of Health [2U01CA70095]; National Cancer Institute [U01 CA70095]; National Cancer Institute Cancer Center [2P30 CA069773-45]; National Center for Research [UL1 RR025005]; J.P. McCarthy Foundation FX This work was supported by the National Institutes of Health (grant 2U01CA70095), the National Cancer Institute (Cooperative Agreement U01 CA70095) (J.E.K., M.A.R.), National Cancer Institute Cancer Center Support (grant 2P30 CA069773-45), National Center for Research (resources grant UL1 RR025005), the J.P. McCarthy Foundation (L.S.R., J.E.K.), and Dr Robert E. Fischell in memory of his late wife Marian (philanthropic funds) (J.E.K.). NR 45 TC 46 Z9 46 U1 0 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 24 PY 2011 VL 117 IS 12 BP 3302 EP 3310 DI 10.1182/blood-2010-09-310862 PG 9 WC Hematology SC Hematology GA 741FJ UT WOS:000288848500013 PM 21239698 ER PT J AU Oh, U McCormick, MJ Datta, D Turner, RV Bobb, K Monie, DD Sliskovic, DR Tanaka, Y Zhang, J Meshulam, J Jacobson, S AF Oh, Unsong McCormick, Matthew J. Datta, Dibyadeep Turner, Richard V. Bobb, Kathryn Monie, Dileep D. Sliskovic, D. Robert Tanaka, Yuetsu Zhang, Jie Meshulam, Jeffrey Jacobson, Steven TI Inhibition of immune activation by a novel nuclear factor-kappa B inhibitor in HTLV-I-associated neurologic disease SO BLOOD LA English DT Article ID MYELOPATHY/TROPICAL SPASTIC PARAPARESIS; CELL LEUKEMIA-CELLS; T-CELLS; VIRUS TYPE-1; SPONTANEOUS PROLIFERATION; IL-2 RECEPTOR; MESSENGER-RNA; TAX PROTEIN; IKK-ALPHA; GENE AB The human T-lymphotropic virus type I (HTLV-I) causes a chronic inflammatory disorder of the central nervous system termed HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-I encodes a protein known to activate several host-signaling pathways involved in inflammation, such as the nuclear factor-kappa B (NF-kappa B). The contribution of the NF-kappa B pathway to the pathogenesis of HAM/TSP, however, has not been fully defined. We show evidence of canonical NF-kappa B activation in short-term cultures of peripheral blood mononuclear cells (PBMCs) from subjects with HAM/TSP. NF-kappa B activation was closely linked to HTLV-I viral protein expression. The NF-kappa B activation in HAM/TSP PBMCs was reversed by a novel small-molecule inhibitor that demonstrates potent and selective NF-kappa B antagonist activity. Inhibition of NF-kappa B activation led to a reduction in the expression of lymphocyte activation markers and resulted in reduced cytokine signaling in HAM/TSP PBMCs. Furthermore, NF-kappa B inhibition led to a reduction in spontaneous lymphoproliferation, a key ex vivo correlate of the immune activation associated with HAM/TSP. These results indicate that NF-kappa B activation plays a critical upstream role in the immune activation of HAM/TSP, and identify the NF-kappa B pathway as a potential target for immunomodulation in HAM/TSP. (Blood. 2011;117(12):3363-3369) C1 [Oh, Unsong; McCormick, Matthew J.; Datta, Dibyadeep; Turner, Richard V.; Jacobson, Steven] Natl Inst Neurol Disorders & Stroke, Neuroimmunol Branch, NIH, Bethesda, MD USA. [Bobb, Kathryn; Monie, Dileep D.; Zhang, Jie; Meshulam, Jeffrey] Profectus BioSci Inc, Baltimore, MD USA. [Sliskovic, D. Robert] Int Discovery Serv & Consulting LLC, Chelsea, MI USA. [Tanaka, Yuetsu] Univ Ryukyus, Grad Sch, Dept Immunol, Okinawa, Japan. [Tanaka, Yuetsu] Univ Ryukyus, Fac Med, Okinawa, Japan. RP Jacobson, S (reprint author), 10 Ctr Dr,Bldg 10,Rm 5C103, Bethesda, MD USA. EM jacobsons@ninds.nih.gov FU National Institutes of Health, National Institute of Neurological Disorders and Stroke (NINDS); Profectus Biosciences Inc. FX This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Neurological Disorders and Stroke (NINDS), and in part by Profectus Biosciences Inc. NR 32 TC 7 Z9 8 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 24 PY 2011 VL 117 IS 12 BP 3363 EP 3369 DI 10.1182/blood-2010-10-306571 PG 7 WC Hematology SC Hematology GA 741FJ UT WOS:000288848500019 PM 21212284 ER PT J AU Weisenburger, DD Savage, KJ Harris, NL Gascoyne, RD Jaffe, ES MacLennan, KA Rudiger, T Pileri, S Nakamura, S Nathwani, B Campo, E Berger, F Coiffier, B Kim, WS Holte, H Federico, M Au, WY Tobinai, K Armitage, JO Vose, JM AF Weisenburger, Dennis D. Savage, Kerry J. Harris, Nancy Lee Gascoyne, Randy D. Jaffe, Elaine S. MacLennan, Kenneth A. Ruediger, Thomas Pileri, Stefano Nakamura, Shigeo Nathwani, Bharat Campo, Elias Berger, Francoise Coiffier, Bertrand Kim, Won-Seog Holte, Harald Federico, Massimo Au, Wing Y. Tobinai, Kensei Armitage, James O. Vose, Julie M. CA Int Peripheral T-Cell Lymphoma Pro TI Peripheral T-cell lymphoma, not otherwise specified: a report of 340 cases from the International Peripheral T-cell Lymphoma Project SO BLOOD LA English DT Article ID NON-HODGKINS-LYMPHOMA; PROGNOSTIC-FACTORS; CLINICAL-FEATURES; CLINICOPATHOLOGICAL FEATURES; REAL CLASSIFICATION; JAPANESE PATIENTS; UNITED-STATES; SINGLE-CENTER; EXPRESSION; OUTCOMES AB The International Peripheral T-cell Lymphoma Project is a collaborative effort to better understand peripheral T-cell lymphoma (PTCL). A total of 22 institutions submitted clinical and pathologic material on 1314 cases. One objective was to analyze the clinical and pathologic features of 340 cases of PTCL, not otherwise specified. The median age of the patients was 60 years, and the majority (69%) presented with advanced stage disease. Most patients (87%) presented with nodal disease, but extranodal disease was present in 62%. The 5-year overall survival was 32%, and the 5-year failure-free survival was only 20%. The majority of patients (80%) were treated with combination chemotherapy that included an anthracycline, but there was no survival advantage. The International Prognostic Index (IPI) was predictive of both overall survival and failure-free survival (P < .001). Multivariate analysis of clinical and pathologic prognostic factors, respectively, when controlling for the IPI, identified bulky disease (>= 10 cm), thrombocytopenia (< 150 x 10(9)/L), and a high number of transformed tumor cells (> 70%) as adverse predictors of survival, but only the latter was significant in final analysis. Thus, the IPI and a single pathologic feature could be used to stratify patients with PTCL-not otherwise specified for novel and risk-adapted therapies. (Blood. 2011;117(12):3402-3408) C1 [Savage, Kerry J.] British Columbia Canc Agcy, Dept Med Oncol, Vancouver, BC V5Z 4E6, Canada. [Harris, Nancy Lee] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Harris, Nancy Lee] Harvard Univ, Sch Med, Boston, MA USA. [Gascoyne, Randy D.] British Columbia Canc Agcy, Dept Pathol, Vancouver, BC V5Z 4E6, Canada. [Jaffe, Elaine S.] NCI, Dept Hematopathol, Bethesda, MD 20892 USA. [MacLennan, Kenneth A.] St James Univ Hosp, Sect Pathol, Leeds LS9 7TF, W Yorkshire, England. [MacLennan, Kenneth A.] St James Univ Hosp, Leeds Inst Mol Med, Leeds LS9 7TF, W Yorkshire, England. [Ruediger, Thomas] Stadt Klinikum Karlsruhe, Inst Pathol, Karlsruhe, Germany. [Pileri, Stefano] Univ Bologna Hosp, Dept Pathol, Bologna, Italy. [Weisenburger, Dennis D.] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA. [Nakamura, Shigeo] Nagoya Univ Hosp, Dept Pathol & Lab Med, Nagoya, Aichi, Japan. [Nathwani, Bharat] Cedars Sinai Med Ctr, Dept Pathol, Los Angeles, CA 90048 USA. [Nathwani, Bharat] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Campo, Elias] Univ Barcelona, Hosp Clin, Dept Pathol, Barcelona, Spain. [Berger, Francoise] Ctr Hosp Lyon Sud, Dept Pathol, Lyon, France. [Coiffier, Bertrand] Ctr Hosp Lyon Sud, Dept Med, Lyon, France. [Kim, Won-Seog] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Div Hematol Oncol, Seoul, South Korea. [Holte, Harald] Norwegian Radium Hosp, Dept Oncol, Oslo, Norway. [Holte, Harald] Oslo Univ Hosp, Oslo, Norway. [Federico, Massimo] Modena Hosp, Dept Med, Modena, Italy. [Au, Wing Y.] Queen Mary Hosp, Dept Med, Hong Kong, Hong Kong, Peoples R China. [Tobinai, Kensei] Natl Canc Ctr, Hematol & Stem Cell Transplantat Div, Tokyo, Japan. [Armitage, James O.; Vose, Julie M.] Univ Nebraska Med Ctr, Dept Internal Med, Omaha, NE 68198 USA. RP Weisenburger, DD (reprint author), Univ Nebraska Med Ctr, Dept Pathol & Microbiol, 983135 Nebraska Med Ctr, Omaha, NE 68198 USA. EM dweisenb@unmc.edu RI Federico, Massimo/A-6801-2012; Nakamura, Shigeo/I-1571-2012; Federico, Massimo/J-5984-2014; Cuadros, Marta/K-1576-2014; Zinzani, Pier Luigi/J-9182-2016; OI Federico, Massimo/0000-0002-9889-3796; Federico, Massimo/0000-0002-5074-3262; Cuadros, Marta/0000-0002-8329-4854; Zinzani, Pier Luigi/0000-0002-2112-2651; Jaffe, Elaine/0000-0003-4632-0301; Campo, elias/0000-0001-9850-9793 NR 39 TC 121 Z9 129 U1 0 U2 10 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 24 PY 2011 VL 117 IS 12 BP 3402 EP 3408 DI 10.1182/blood-2010-09-310342 PG 7 WC Hematology SC Hematology GA 741FJ UT WOS:000288848500023 PM 21270441 ER PT J AU McCormack, M Alfirevic, A Bourgeois, S Farrell, JJ Kasperaviciute, D Carrington, M Sills, GJ Marson, T Jia, XM de Bakker, PIW Chinthapalli, K Molokhia, M Johnson, MR O'Connor, GD Chaila, E Alhusaini, S Shianna, KV Radtke, RA Heinzen, EL Walley, N Pandolfo, M Pichler, W Park, BK Depondt, C Sisodiya, SM Goldstein, DB Deloukas, P Delanty, N Cavalleri, GL Pirmohamed, M AF McCormack, Mark Alfirevic, Ana Bourgeois, Stephane Farrell, John J. Kasperaviciute, Dalia Carrington, Mary Sills, Graeme J. Marson, Tony Jia, Xiaoming de Bakker, Paul I. W. Chinthapalli, Krishna Molokhia, Mariam Johnson, Michael R. O'Connor, Gerard D. Chaila, Elijah Alhusaini, Saud Shianna, Kevin V. Radtke, Rodney A. Heinzen, Erin L. Walley, Nicole Pandolfo, Massimo Pichler, Werner Park, B. Kevin Depondt, Chantal Sisodiya, Sanjay M. Goldstein, David B. Deloukas, Panos Delanty, Norman Cavalleri, Gianpiero L. Pirmohamed, Munir TI HLA-A*3101 and Carbamazepine-Induced Hypersensitivity Reactions in Europeans SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID STEVENS-JOHNSON-SYNDROME; TOXIC EPIDERMAL NECROLYSIS; ADVERSE DRUG-REACTIONS; HUMAN-LEUKOCYTE ANTIGEN-B-ASTERISK-5701; GENERALIZED EXANTHEMATOUS PUSTULOSIS; INDUCED LIVER-INJURY; HLA-B; ABACAVIR HYPERSENSITIVITY; COST-EFFECTIVENESS; DRESS SYNDROME AB BACKGROUND Carbamazepine causes various forms of hypersensitivity reactions, ranging from maculopapular exanthema to severe blistering reactions. The HLA-B*1502 allele has been shown to be strongly correlated with carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS-TEN) in the Han Chinese and other Asian populations but not in European populations. METHODS We performed a genomewide association study of samples obtained from 22 subjects with carbamazepine-induced hypersensitivity syndrome, 43 subjects with carbamazepine-induced maculopapular exanthema, and 3987 control subjects, all of European descent. We tested for an association between disease and HLA alleles through proxy single-nucleotide polymorphisms and imputation, confirming associations by high-resolution sequence-based HLA typing. We replicated the associations in samples from 145 subjects with carbamazepine-induced hypersensitivity reactions. RESULTS The HLA-A*3101 allele, which has a prevalence of 2 to 5% in Northern European populations, was significantly associated with the hypersensitivity syndrome (P = 3.5x10(-8)). An independent genomewide association study of samples from subjects with maculopapular exanthema also showed an association with the HLAA*3101 allele (P = 1.1x10(-6)). Follow-up genotyping confirmed the variant as a risk factor for the hypersensitivity syndrome (odds ratio, 12.41; 95% confidence interval [CI], 1.27 to 121.03), maculopapular exanthema (odds ratio, 8.33; 95% CI, 3.59 to 19.36), and SJS-TEN (odds ratio, 25.93; 95% CI, 4.93 to 116.18). CONCLUSIONS The presence of the HLA-A* 3101 allele was associated with carbamazepine-induced hypersensitivity reactions among subjects of Northern European ancestry. The presence of the allele increased the risk from 5.0% to 26.0%, whereas its absence reduced the risk from 5.0% to 3.8%. C1 [Alfirevic, Ana] Univ Liverpool, Wolfson Ctr Personalised Med, Dept Mol & Clin Pharmacol, Inst Translat Med, Liverpool L69 3GL, Merseyside, England. [McCormack, Mark; Alhusaini, Saud; Delanty, Norman; Cavalleri, Gianpiero L.] Royal Coll Surgeons Ireland, Dublin 2, Ireland. [O'Connor, Gerard D.; Chaila, Elijah; Delanty, Norman] Beaumont Hosp, Div Neurol, Dublin 9, Ireland. [Marson, Tony] Walton Ctr Neurol, Liverpool, Merseyside, England. [Bourgeois, Stephane; Deloukas, Panos] Wellcome Trust Sanger Inst, Hinxton, England. [Chinthapalli, Krishna; Sisodiya, Sanjay M.] Natl Soc Epilepsy, Gerrards Cross, Bucks, England. [Farrell, John J.] Boston Univ, Dept Med, Boston, MA 02215 USA. [Carrington, Mary] Harvard Univ, Massachusetts Gen Hosp, MIT, Sch Med,Ragon Inst, Boston, MA USA. [Jia, Xiaoming] Harvard Univ, Sch Med, Harvard MIT Div Hlth Sci & Technol, Boston, MA 02115 USA. [de Bakker, Paul I. W.] Harvard Univ, Brigham & Womens Hosp, Div Genet, Dept Med,Med Sch, Boston, MA 02115 USA. [Kasperaviciute, Dalia; Chinthapalli, Krishna; Sisodiya, Sanjay M.] UCL, Dept Clin & Expt Epilepsy, Inst Neurol, London, England. [Molokhia, Mariam] Kings Coll London, Dept Primary Care & Publ Hlth Sci, Div Hlth & Social Care Res, London WC2R 2LS, England. [Johnson, Michael R.] Univ London Imperial Coll Sci Technol & Med, Dept Med, Ctr Neurosci, London, England. [Carrington, Mary] NCI, Canc & Inflammat Program, Lab Expt Immunol, SAIC Frederick, Frederick, MD 21701 USA. [de Bakker, Paul I. W.] Harvard & MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [de Bakker, Paul I. W.] Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. [de Bakker, Paul I. W.] Univ Med Ctr, Dept Med Genet, Div Biomed Genet, Utrecht, Netherlands. [Shianna, Kevin V.; Heinzen, Erin L.; Walley, Nicole; Goldstein, David B.] Duke Univ, Sch Med, Ctr Human Genome Variat, Durham, NC USA. [Radtke, Rodney A.] Duke Univ, Sch Med, Dept Med Neurol, Durham, NC USA. [Pandolfo, Massimo; Depondt, Chantal] Univ Libre Bruxelles, Dept Neurol, Hop Erasme, Brussels, Belgium. [Pichler, Werner] Univ Bern, Dept Rheumatol Clin Immunol & Allergol, Bern, Switzerland. RP Alfirevic, A (reprint author), Univ Liverpool, Wolfson Ctr Personalised Med, Dept Mol & Clin Pharmacol, Inst Translat Med, Block A,Waterhouse Bldgs,1-5 Brownlow St, Liverpool L69 3GL, Merseyside, England. EM ana.alfirevic@liv.ac.uk RI Cavalleri, Gianpiero/A-6632-2010; Pirmohamed, Munir/H-6004-2011; Deloukas, Panos/B-2922-2013; de Bakker, Paul/B-8730-2009; McCormack, Mark/A-5482-2010; OI Pirmohamed, Munir/0000-0002-7534-7266; Deloukas, Panos/0000-0001-9251-070X; de Bakker, Paul/0000-0001-7735-7858; McCormack, Mark/0000-0002-8213-6141; Delaney, Norman/0000-0002-3953-9842; Cavalleri, Gianpiero/0000-0002-9802-0506 FU U.K. Department of Health; Department of Health; National Health Service Chair of Pharmacogenetics; Medical Research Council Centre for Drug Safety Science; Wolfson Foundation; Wellcome Trust Sanger Institute; National Institute for Health Research; Medical Research Council [G0400126]; Wellcome Trust [084730]; University College London Hospitals Charity; Clinical Research and Development Committee [F136]; National Institute for Health Research [08-08-SCC]; Brainwave-the Irish Epilepsy Association [2009/001]; Medical Research Charities Group of Ireland; Health Research Board; National Society for Epilepsy; Fonds National de la Recherche Scientifique; Fonds Erasme pour la Recherche Medicale; Universite Libre de Bruxelles (Belgium); Health Research Board of Ireland; Department of Health National Institute for Health Research Biomedical Research Centres; National Cancer Institute [HHS-N261200800001E]; National Cancer Institute, National Institutes of Health FX Funded by the U.K. Department of Health and others.; Supported by grants to the Liverpool collaborators from the Department of Health, the National Health Service Chair of Pharmacogenetics, the Medical Research Council Centre for Drug Safety Science, the Wolfson Foundation, the Wellcome Trust Sanger Institute, and the National Institute for Health Research (to Dr. Pirmohamed); by grants to the EPIGEN consortium from the Medical Research Council (G0400126), the Wellcome Trust (084730), University College London Hospitals Charity, Clinical Research and Development Committee (F136), and the National Institute for Health Research (08-08-SCC); by an award (2009/001) from Brainwave-the Irish Epilepsy Association; by the Medical Research Charities Group of Ireland, the Health Research Board, the National Society for Epilepsy, Fonds National de la Recherche Scientifique, and Fonds Erasme pour la Recherche Medicale, Universite Libre de Bruxelles (Belgium); by a Translational Research Scholars award from the Health Research Board of Ireland (to Mr. McCormack); by the Department of Health National Institute for Health Research Biomedical Research Centres; and by a contract from the National Cancer Institute (HHS-N261200800001E) and the Intramural Research Program at the National Cancer Institute, National Institutes of Health. NR 40 TC 327 Z9 344 U1 6 U2 32 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 24 PY 2011 VL 364 IS 12 BP 1134 EP 1143 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 739FY UT WOS:000288701100008 PM 21428769 ER PT J AU Qiang, W Yau, WM Tycko, R AF Qiang, Wei Yau, Wai-Ming Tycko, Robert TI Structural Evolution of Iowa Mutant beta-Amyloid Fibrils from Polymorphic to Homogeneous States under Repeated Seeded Growth SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; MOLECULAR-DYNAMICS SIMULATIONS; SHEET STRUCTURE; THIOFLAVIN-T; SECONDARY-STRUCTURE; ROTATING SOLIDS; PEPTIDE; PARALLEL; PROTEIN; PRION AB Structural variations in beta-amyloid fibrils are potentially important to the toxicity of these fibrils in Alzheimer's disease (AD). We describe a repeated seeding protocol that selects a homogeneous fibril structure from a polymorphic initial state in the case of 40-residue beta-amyloid fibrils with the Asp23-to-Asn, or Iowa, mutation (D23N-A beta(1-40)). We use thioflavin T (ThT) fluorescence, transmission electron microscopy (TEM), and solid-state nuclear magnetic resonance (NMR) to track the evolution of fibril structure through multiple generations under this protocol. The data show that (i) repeated seeding selectively amplifies a single D23N-A beta(1-40) fibril structure that can be a minor component of the initial polymorphic state; (ii) the final structure is highly sensitive to growth conditions, including pH, temperature, and agitation; (iii) although the initial state can include fibrils that contain both antiparallel and parallel beta-sheets, the final structures contain only parallel beta-sheets, suggesting that antiparallel beta-sheet structures are thermodynamically and kinetically metastable. Additionally, our data demonstrate that ThT fluorescence enhancements, which are commonly used to monitor amyloid fibril formation, vary strongly with structural variations, even among fibrils comprised of the same polypeptide. Finally, we present a simple mathematical model that describes the structural evolution of fibril samples under repeated seeding. C1 [Qiang, Wei; Yau, Wai-Ming; Tycko, Robert] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Tycko, R (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA. EM robertty@mail.nih.gov RI Qiang, Wei/I-1053-2012 FU National Institute of Diabetes and Digestive and Kidney Diseases 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 of the National Institutes of Health. NR 57 TC 43 Z9 43 U1 0 U2 25 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD MAR 23 PY 2011 VL 133 IS 11 BP 4018 EP 4029 DI 10.1021/ja109679q PG 12 WC Chemistry, Multidisciplinary SC Chemistry GA 741UF UT WOS:000288889900061 PM 21355554 ER PT J AU Tsujimoto, S Genovesio, A Wise, SP AF Tsujimoto, Satoshi Genovesio, Aldo Wise, Steven P. TI Comparison of Strategy Signals in the Dorsolateral and Orbital Prefrontal Cortex SO JOURNAL OF NEUROSCIENCE LA English DT Article ID MONKEY ORBITOFRONTAL CORTEX; WORKING-MEMORY; NEURONAL-ACTIVITY; MACAQUE MONKEY; FRONTAL-CORTEX; ABSTRACT RULES; ECONOMIC VALUE; NONHUMAN-PRIMATES; DISSOCIABLE ROLES; REWARD PREFERENCE AB behavior-guiding rules and strategies allow monkeys to avoid errors in rarely encountered situations. In the present study, we contrasted strategy-related neuronal activity in the dorsolateral prefrontal cortex (PFdl) and the orbital prefrontal cortex (PFo) of rhesus monkeys. On each trial of their behavioral task, the monkeys responded to a foveal visual cue by making a saccade to one of two spatial targets. One response required a leftward saccade, the other required a saccade of equal magnitude to the right. The cues instructed the monkeys to follow one of two response strategies: to stay with their most recent successful response or to shift to the alternative response. Neurons in both areas encoded the stay and shift strategies after the cue appeared, but there were three major differences between the PFo and the PFdl: (1) manystrategy-encoding cells in PFdl also encoded the response (left or right), but few, if any, PFo cells did so; (2) strategy selectivity appeared earlier in PFo than in PFdl; and (3) on error trials, PFo neurons encoded the correct strategy-the one that had been cued but not implemented-whereas in PFdl the strategy signals were weak or absent on error trials. These findings indicate that PFo and PFdl both contribute to behaviors guided by abstract response strategies, but do so differently, with PFo encoding a strategy and PFdl encoding a response based on a strategy. C1 [Tsujimoto, Satoshi] Kobe Univ, Grad Sch Human Dev & Environm, Dept Hlth Promot & Educ, Dev Cognit Neurosci Lab,Nada Ku, Kobe, Hyogo 6578501, Japan. [Tsujimoto, Satoshi; Genovesio, Aldo; Wise, Steven P.] NIMH, Lab Syst Neurosci, NIH, Bethesda, MD 20892 USA. [Genovesio, Aldo] Univ Roma La Sapienza, Dept Physiol & Pharmacol, I-00185 Rome, Italy. RP Tsujimoto, S (reprint author), Kobe Univ, Grad Sch Human Dev & Environm, Dept Hlth Promot & Educ, Dev Cognit Neurosci Lab,Nada Ku, 3-11 Tsurukabuto, Kobe, Hyogo 6578501, Japan. EM tsujimoto@ruby.kobe-u.ac.jp RI Tsujimoto, Satoshi/B-8223-2011 FU Division of Intramural Research of the National Institute of Mental Health [Z01MH-01092]; Ministry of Education, Culture, Sports, Science and Technology [21119513]; Japan Society for the Promotion of Science [22700340] FX This work was supported by the Division of Intramural Research of the National Institute of Mental Health (Z01MH-01092) and by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology (21119513) and Japan Society for the Promotion of Science (22700340). We thank Dr. Andrew R. Mitz, James Fellows, and Ping-Yu Chen for technical support. NR 73 TC 25 Z9 25 U1 0 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR 23 PY 2011 VL 31 IS 12 BP 4583 EP 4592 DI 10.1523/JNEUROSCI.5816-10.2011 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 739WD UT WOS:000288750700024 PM 21430158 ER PT J AU Thomas, CG Tian, H Diamond, JS AF Thomas, Christopher G. Tian, Hua Diamond, Jeffrey S. TI The Relative Roles of Diffusion and Uptake in Clearing Synaptically Released Glutamate Change during Early Postnatal Development SO JOURNAL OF NEUROSCIENCE LA English DT Article ID HIPPOCAMPAL DENDRITIC SPINES; LONG-TERM POTENTIATION; NMDA RECEPTORS; TIME-COURSE; RAT-BRAIN; QUANTITATIVE-ANALYSIS; TRANSPORTER CURRENTS; EXPRESSION; SYNAPSES; ASTROCYTES AB Glutamate uptake by transporters expressed in astrocytes combines with synaptic structure to regulate the time that synaptically released glutamate remains in the extracellular space and, consequently, the duration and location of postsynaptic receptor activation. Both factors change greatly in the rodent hippocampus during the second postnatal week when most synapses become established and begin to mature, processes that are influenced by synaptically released glutamate. Transporter expression increases, potentially speeding removal of synaptically released glutamate, whereas extracellular space decreases, thereby slowing dilution. We investigated whether these competing changes influence the glutamate concentration time course and postsynaptic responses in the CA1 region of the mouse hippocampus during this critical period of synaptic development. Our results suggest that the glutamate concentration time course remains relatively consistent over this period, although the primary mechanisms regulating glutamate clearance change. Before the second postnatal week, clearance of synaptically released glutamate depends primarily on diffusion into large extracellular spaces, whereas later in development it relies more on increased uptake capacity. Thus, increased transporter expression during this period accompanies structural changes in the neuropil, preserving a relatively consistent glutamate concentration time course and ensuring that postsynaptic receptor activation remains brief and primarily localized to receptors close to release sites. C1 [Thomas, Christopher G.; Tian, Hua; Diamond, Jeffrey S.] Natl Inst Neurol Disorders & Stroke, Synapt Physiol Sect, NIH, Bethesda, MD 20892 USA. RP Diamond, JS (reprint author), Bldg 35,Room 3C-1000,35 Convent Dr, Bethesda, MD 20892 USA. EM diamondj@ninds.nih.gov RI Diamond, Jeffrey/C-1835-2015 OI Diamond, Jeffrey/0000-0002-1770-2629 FU National Institute of Neurological Disorders and Stroke; Human Frontier Science Program FX This work was supported by the National Institute of Neurological Disorders and Stroke Intramural Research Program and the Human Frontier Science Program. We thank J.-H. Tao-Cheng, and Rita Azzam for help with electron microscopy, Carolyn Smith for help with confocal imaging, and S. Brian Andrews, William N. Grimes, William W. Kothmann, Nick Oesch, Syed Qadri, and Annalisa Scimemi for valuable discussions and helpful comments on this manuscript. NR 63 TC 33 Z9 33 U1 0 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR 23 PY 2011 VL 31 IS 12 BP 4743 EP 4754 DI 10.1523/JNEUROSCI.5953-10.2011 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 739WD UT WOS:000288750700039 PM 21430173 ER PT J AU Subramanian, J Morozov, A AF Subramanian, Jaichandar Morozov, Alexei TI Erk1/2 Inhibit Synaptic Vesicle Exocytosis through L-Type Calcium Channels SO JOURNAL OF NEUROSCIENCE LA English DT Article ID CA2+ CHANNELS; NEUROTRANSMITTER RELEASE; PRESYNAPTIC PLASTICITY; HIPPOCAMPAL SYNAPSES; NERVE-TERMINALS; CNS SYNAPSES; IN-VIVO; N-TYPE; TRANSMISSION; ENDOCYTOSIS AB L-type calcium channels play only a minor role in basal neurotransmitter release in brain neurons but contribute significantly after induction of plasticity. Very little is known about mechanisms that enable L-type calcium channel participation in neurotransmitter release. Here, using mouse primary cortical neurons, we found that inhibition of Erk1/2 (extracellular signal-regulated kinases 1 and 2) enhanced synaptic vesicle exocytosis by increasing calcium influx through L-type calcium channels. Furthermore, inhibition of Erk1/2 increased the surface fraction of these channels. These findings indicate a novel inhibitory effect of Erk1/2 on synaptic transmission through L-type calcium channels. C1 [Subramanian, Jaichandar; Morozov, Alexei] NIMH, Unit Behav Genet, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Subramanian, J (reprint author), NIMH, Unit Behav Genet, Mol Pathophysiol Lab, NIH, 35 Convent Dr, Bethesda, MD 20892 USA. EM subramanianj@mail.nih.gov; morozova@mail.nih.gov FU National Institute of Mental Health FX This work was supported by National Institute of Mental Health intramural research program. Cell culture and imaging were performed at the Microscopy and Imaging Core (National Institute of Child Health and Human Development, National Institutes of Health) with the help of Dr. Vincent Schram, Chip Dye, Lynne Holtzclaw, and Dr. James T. Russell and at the Light Imaging Facility (National Institute of Neurological Disorders and Stroke, National Institutes of Health) with the help of Dr. Carolyn Smith. NR 39 TC 12 Z9 12 U1 0 U2 1 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 MAR 23 PY 2011 VL 31 IS 12 BP 4755 EP 4764 DI 10.1523/JNEUROSCI.6594-10.2011 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 739WD UT WOS:000288750700040 PM 21430174 ER PT J AU Resnik, DB Koski, G AF Resnik, David B. Koski, Greg TI A National Registry for Healthy Volunteers in Phase 1 Clinical Trials SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 [Resnik, David B.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Koski, Greg] Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Mongan Inst Hlth Policy, Boston, MA USA. [Koski, Greg] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. RP Resnik, DB (reprint author), NIEHS, NIH, POB 12233,Mail Drop CU03, Res Triangle Pk, NC 27709 USA. EM resnikd@niehs.nih.gov FU Intramural NIH HHS [ZIA ES102646-01, ZIA ES102646-02] NR 9 TC 17 Z9 17 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 23 PY 2011 VL 305 IS 12 BP 1236 EP 1237 DI 10.1001/jama.2011.354 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 738PA UT WOS:000288652100020 PM 21406636 ER PT J AU Gong, T Xuan, JH Chen, L Riggins, RB Li, HA Hoffman, EP Clarke, R Wang, Y AF Gong, Ting Xuan, Jianhua Chen, Li Riggins, Rebecca B. Li, Huai Hoffman, Eric P. Clarke, Robert Wang, Yue TI Motif-guided sparse decomposition of gene expression data for regulatory module identification SO BMC BIOINFORMATICS LA English DT Article ID TRANSCRIPTION FACTOR-BINDING; GROWTH-FACTOR RECEPTOR; BREAST-CANCER CELLS; NETWORK COMPONENT ANALYSIS; ESTROGEN-RECEPTOR; MICROARRAY DATA; SACCHAROMYCES-CEREVISIAE; FUNCTIONAL INTERACTIONS; MATRIX FACTORIZATION; SIGNAL TRANSDUCER AB Background: Genes work coordinately as gene modules or gene networks. Various computational approaches have been proposed to find gene modules based on gene expression data; for example, gene clustering is a popular method for grouping genes with similar gene expression patterns. However, traditional gene clustering often yields unsatisfactory results for regulatory module identification because the resulting gene clusters are co-expressed but not necessarily co-regulated. Results: We propose a novel approach, motif-guided sparse decomposition (mSD), to identify gene regulatory modules by integrating gene expression data and DNA sequence motif information. The mSD approach is implemented as a two-step algorithm comprising estimates of (1) transcription factor activity and (2) the strength of the predicted gene regulation event(s). Specifically, a motif-guided clustering method is first developed to estimate the transcription factor activity of a gene module; sparse component analysis is then applied to estimate the regulation strength, and so predict the target genes of the transcription factors. The mSD approach was first tested for its improved performance in finding regulatory modules using simulated and real yeast data, revealing functionally distinct gene modules enriched with biologically validated transcription factors. We then demonstrated the efficacy of the mSD approach on breast cancer cell line data and uncovered several important gene regulatory modules related to endocrine therapy of breast cancer. Conclusion: We have developed a new integrated strategy, namely motif-guided sparse decomposition (mSD) of gene expression data, for regulatory module identification. The mSD method features a novel motif-guided clustering method for transcription factor activity estimation by finding a balance between co-regulation and co-expression. The mSD method further utilizes a sparse decomposition method for regulation strength estimation. The experimental results show that such a motif-guided strategy can provide context-specific regulatory modules in both yeast and breast cancer studies. C1 [Gong, Ting; Xuan, Jianhua; Chen, Li; Wang, Yue] Virginia Tech, Bradley Dept Elect & Comp Engn, Arlington, VA 22203 USA. [Riggins, Rebecca B.; Clarke, Robert] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. [Riggins, Rebecca B.; Clarke, Robert] Georgetown Univ, Dept Oncol Physiol & Biophys, Washington, DC 20057 USA. [Li, Huai] NIA, Bioinformat Unit, RRB, NIH, Baltimore, MD 21224 USA. [Hoffman, Eric P.] Childrens Natl Med Ctr, Med Genet Res Ctr, Washington, DC 20010 USA. RP Xuan, JH (reprint author), Virginia Tech, Bradley Dept Elect & Comp Engn, Arlington, VA 22203 USA. EM xuan@vt.edu RI Clarke, Robert/A-6485-2008; Chen, Li/P-5945-2014 OI Clarke, Robert/0000-0002-9278-0854; FU National Institutes of Health [CA139246, CA149147, CA109872, CA149653, NS29525, EB000830, CA096483]; Department of Defense [BC030280] FX This study is supported by the National Institutes of Health under Grants (CA139246, CA149147, CA109872, CA149653, NS29525, EB000830 and CA096483) and the Department of Defense under Grant (BC030280). We thank Alan Zwart for his work in the acquisition of breast cancer cell line microarray data. We also thank the reviewers for their invaluable suggestions that lead to many improvements in the manuscript. NR 72 TC 7 Z9 7 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD MAR 22 PY 2011 VL 12 AR 82 DI 10.1186/1471-2105-12-82 PG 16 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 746RF UT WOS:000289263700001 PM 21426557 ER PT J AU Silverman, JL Turner, SM Barkan, CL Tolu, SS Saxena, R Hung, AY Sheng, M Crawley, JN AF Silverman, Jill L. Turner, Sarah M. Barkan, Charlotte L. Tolu, Seda S. Saxena, Roheeni Hung, Albert Y. Sheng, Morgan Crawley, Jacqueline N. TI Sociability and motor functions in Shank1 mutant mice SO BRAIN RESEARCH LA English DT Article ID AUTISM SPECTRUM DISORDERS; ANXIETY-LIKE BEHAVIOR; INBRED MOUSE STRAINS; OVEREXPRESSING TRANSGENIC MICE; ELEVATED PLUS-MAZE; BTBR-T+TF/J MICE; POSTSYNAPTIC DENSITY; REPETITIVE BEHAVIOR; SOCIAL APPROACH; KNOCKOUT MICE AB Autism is a neurodevelopmental disorder characterized by aberrant reciprocal social interactions, impaired communication, and repetitive behaviors. While the etiology remains unclear, strong evidence exists for a genetic component, and several synaptic genes have been implicated. SHANK genes encode a family of synaptic scaffolding proteins located postsynaptically on excitatory synapses. Mutations in SHANK genes have been detected in several autistic individuals. To understand the consequences of SHANK mutations relevant to the diagnostic and associated symptoms of autism, comprehensive behavioral phenotyping on a line of Shank1 mutant mice was conducted on multiple measures of social interactions, social olfaction, repetitive behaviors, anxiety-related behaviors, motor functions, and a series of control measures for physical abilities. Results from our comprehensive behavioral phenotyping battery indicated that adult Shank1 null mutant mice were similar to their wildtype and heterozygous littermates on standardized measures of general health, neurological reflexes and sensory skills. Motor functions were reduced in the null mutants on open field activity, rotarod, and wire hang, replicating and extending previous findings (Hung et al., 2008). A partial anxiety-like phenotype was detected in the null mutants in some components of the light - dark task, as previously reported (Hung et al., 2008) but not in the elevated plus-maze. juvenile reciprocal social interactions did not differ across genotypes. Interpretation of adult social approach was confounded by a lack of normal sociability in wildtype and heterozygous littermates. All genotypes were able to discriminate social odors on an olfactory habituation/dishabituation task. All genotypes displayed relatively high levels of repetitive self-grooming. Our findings support the interpretation that Shank1 null mice do not demonstrate autism-relevant social interaction deficits, but confirm and extend a role for Shank1 in motor functions. Published by Elsevier B.V. C1 [Silverman, Jill L.; Turner, Sarah M.; Barkan, Charlotte L.; Tolu, Seda S.; Saxena, Roheeni; Crawley, Jacqueline N.] NIMH, Lab Behav Neurosci, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Hung, Albert Y.; Sheng, Morgan] MIT, Picower Inst Learning & Memory, Cambridge, MA 02139 USA. RP Silverman, JL (reprint author), NIMH, Lab Behav Neurosci, Intramural Res Program, NIH, Porter Neurosci Res Ctr Bldg 35,Room 1C-909,9000, Bethesda, MD 20892 USA. EM silvermanj@mail.nih.gov FU National Institute of Mental Health; Simons Foundation FX Supported by the National Institute of Mental Health Intramural Research Program and by a Simons Foundation grant to A.H. and M.S. NR 107 TC 87 Z9 87 U1 2 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAR 22 PY 2011 VL 1380 SI SI BP 120 EP 137 DI 10.1016/j.brainres.2010.09.026 PG 18 WC Neurosciences SC Neurosciences & Neurology GA 745AH UT WOS:000289135800011 PM 20868654 ER PT J AU Bernardi, S Anagnostou, E Shen, J Kolevzon, A Buxbaum, JD Hollander, E Hof, PR Fan, J AF Bernardi, Silvia Anagnostou, Evdokia Shen, Jun Kolevzon, Alexander Buxbaum, Joseph D. Hollander, Eric Hof, Patrick R. Fan, Jin TI In vivo H-1-magnetic resonance spectroscopy study of the attentional networks in autism SO BRAIN RESEARCH LA English DT Article DE Autism; Spectroscopy; Glutamate; Anterior cingulate cortex; Temporoparietal junction; Myo-inositol ID ANTERIOR CINGULATE GYRUS; CARRIER SLC25A12 GENE; N-ACETYL ASPARTATE; SPECTRUM DISORDERS; EXECUTIVE FUNCTION; NEURAL MECHANISMS; YOUNG-CHILDREN; BRAIN; GLUTAMATE; DYSFUNCTION AB Attentional dysfunction is one of the most consistent findings in individuals with autism spectrum disorders (ASD). However, the significance of such findings for the pathophysiology of autism is unclear. In this study, we investigated cellular neurochemistry with proton magnetic resonance spectroscopy imaging (H-1-MRS) in brain regions associated with networks subserving alerting, orienting, and executive control of attention in patients with ASD. Concentrations of cerebral N-acetyl-aspartate (NAA), creatinine + phosphocreatinine, choline-containing compounds, myo-inositol (Ins) and glutamate + glutamine (Glx) were determined by 3 T H-1-MRS examinations in 14 high-functioning medication-free adults with a diagnosis of ASD and 14 age- and IQ-matched healthy controls (HC) in the anterior cingulate cortex (ACC), thalamus, temporoparietal junction (TPJ), and areas near or along the intraparietal sulcus (IFS). Compared to HC group, the ASD group showed significantly lower Glx concentration in right ACC and reduced Ins concentration in left TPJ. This study provides evidence of abnormalities in neurotransmission related to networks subserving executive control and alerting of attention, functions which have been previously implicated in ASD pathogenesis. (C) 2010 Elsevier B.V. All rights reserved. C1 [Fan, Jin] CUNY Queens Coll, Dept Psychol, Flushing, NY 11367 USA. [Bernardi, Silvia; Anagnostou, Evdokia; Kolevzon, Alexander; Buxbaum, Joseph D.; Fan, Jin] Mt Sinai Sch Med, Seaver Autism Ctr Res & Treatment, New York, NY 10029 USA. [Bernardi, Silvia; Kolevzon, Alexander; Buxbaum, Joseph D.; Fan, Jin] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Buxbaum, Joseph D.; Hof, Patrick R.; Fan, Jin] Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA. [Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA. [Bernardi, Silvia] Univ Florence, Dept Psychiat, I-50137 Florence, Italy. [Shen, Jun] NIH, Sect Magnet Resonance Spect, Mol Imaging Branch, Bethesda, MD 20892 USA. [Hollander, Eric] Montefiore Med Ctr, Albert Einstein Coll Med, Univ Hosp, Bronx, NY 10467 USA. RP Fan, J (reprint author), CUNY Queens Coll, Dept Psychol, 65-30 Kissena Blvd, Flushing, NY 11367 USA. EM jin.fan@qc.cuny.edu RI Fan, Jin/A-6716-2009 OI Fan, Jin/0000-0001-9630-8330 FU National Center for Research Resources [M01 RR000071]; NARSAD; NIMH [MH083164] FX The study described was supported by National Center for Research Resources Grant M01 RR000071. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NCRR or NIH. This work was also supported in part by a Young Investigator Award from the NARSAD and by an NIMH grant MH083164 to JF. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Dr. Jack M. Gorman for his support. Thanks to Kevin G. Guise, Laura Martin, and Dr. Cheuk Y. Tang for assistance with data collection. We thank the Beatrice and Samuel A. Seaver Foundation. NR 74 TC 47 Z9 49 U1 2 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAR 22 PY 2011 VL 1380 SI SI BP 198 EP 205 DI 10.1016/j.brainres.2010.12.057 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 745AH UT WOS:000289135800017 PM 21185269 ER PT J AU Macadangdang, B Zhang, N Lund, PE Marple, AH Okabe, M Gottesman, MM Appella, DH Kimchi-Sarfaty, C AF Macadangdang, Benjamin Zhang, Ning Lund, Paul E. Marple, Andrew H. Okabe, Mitsunori Gottesman, Michael M. Appella, Daniel H. Kimchi-Sarfaty, Chava TI Inhibition of Multidrug Resistance by SV40 Pseudovirion Delivery of an Antigene Peptide Nucleic Acid (PNA) in Cultured Cells SO PLOS ONE LA English DT Article ID P-GLYCOPROTEIN; GENE-EXPRESSION; IN-VITRO; SV40-DERIVED VECTORS; LOCALIZATION SIGNAL; CELLULAR DELIVERY; ANTICANCER DRUGS; CHROMOSOMAL DNA; CANCER-CELLS; SEQUENCE AB Peptide nucleic acid (PNA) is known to bind with extraordinarily high affinity and sequence-specificity to complementary nucleic acid sequences and can be used to suppress gene expression. However, effective delivery into cells is a major obstacle to the development of PNA for gene therapy applications. Here, we present a novel method for the in vitro delivery of antigene PNA to cells. By using a nucleocapsid protein derived from Simian virus 40, we have been able to package PNA into pseudovirions, facilitating the delivery of the packaged PNA into cells. We demonstrate that this system can be used effectively to suppress gene expression associated with multidrug resistance in cancer cells, as shown by RT-PCR, flow cytometry, Western blotting, and cell viability under chemotherapy. The combination of PNA with the SV40-based delivery system is a method for suppressing a gene of interest that could be broadly applied to numerous targets. C1 [Macadangdang, Benjamin; Lund, Paul E.; Marple, Andrew H.; Okabe, Mitsunori; Gottesman, Michael M.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. [Zhang, Ning; Appella, Daniel H.] NIDDK, Bioorgan Chem Lab, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Kimchi-Sarfaty, Chava] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Macadangdang, B (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. EM appellad@niddk.nih.gov; chava.kimchi-sarfaty@fda.hhs.gov FU National Institutes of Health; National Cancer InstituteNational Institute of Diabetes and Digestive and Kidney Diseases; Food and Drug Administration FX This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, and the National Institute of Diabetes and Digestive and Kidney Diseases, and the Food and Drug Administration. The findings and conclusions in this article have not been formally disseminated by the Food and Drug Administration and should not be construed to represent an Agency determination or policy. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 48 TC 4 Z9 4 U1 1 U2 13 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 22 PY 2011 VL 6 IS 3 AR e17981 DI 10.1371/journal.pone.0017981 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 740QI UT WOS:000288809100021 PM 21445346 ER PT J AU Baldwin, JT Borovetz, HS Duncan, BW Gartner, MJ Jarvik, RK Weiss, WJ AF Baldwin, J. Timothy Borovetz, Harvey S. Duncan, Brian W. Gartner, Mark J. Jarvik, Robert K. Weiss, William J. TI The National Heart, Lung, and Blood Institute Pediatric Circulatory Support Program A Summary of the 5-Year Experience SO CIRCULATION LA English DT Article DE congenital heart disease; extracorporeal circulation; heart failure; pediatrics; ventricular assist device ID VENTRICULAR ASSIST DEVICE; CLEVELAND-CLINIC PEDIPUMP; CHILDREN; MODELS C1 [Baldwin, J. Timothy] NHLBI, Adv Technol & Surg Branch, Div Cardiovasc Sci, Rockledge Ctr 2, Bethesda, MD 20892 USA. [Borovetz, Harvey S.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. [Borovetz, Harvey S.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. [Borovetz, Harvey S.] Univ Pittsburgh, McGowan Inst Regenerat Med, Pittsburgh, PA USA. [Duncan, Brian W.] Cleveland Clin Fdn, Dept Pediat & Congenital Heart Surg, Cleveland, OH 44195 USA. [Duncan, Brian W.] Cleveland Clin Fdn, Dept Biomed Engn, Cleveland, OH 44195 USA. [Gartner, Mark J.] Ension Inc, Pittsburgh, PA USA. [Jarvik, Robert K.] Jarvik Heart Inc, New York, NY USA. [Weiss, William J.] Penn State Univ, Coll Med, Dept Surg, Hershey, PA USA. [Weiss, William J.] Penn State Univ, Coll Med, Dept Bioengn, Hershey, PA USA. RP Baldwin, JT (reprint author), NHLBI, Adv Technol & Surg Branch, Div Cardiovasc Sci, Rockledge Ctr 2, Room 8206,6701 Rockledge Dr, Bethesda, MD 20892 USA. EM baldwint@nhlbi.nih.gov FU NIH [N01 HV48188, N01 HV48189, N01 HV48190, N01 HV48191, N01 HV48192] FX The work described in this manuscript was supported by NIH contracts N01 HV48188, N01 HV48189, N01 HV48190, N01 HV48191, and N01 HV48192. NR 29 TC 48 Z9 48 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 22 PY 2011 VL 123 IS 11 BP 1233 EP 1240 DI 10.1161/CIRCULATIONAHA.110.978023 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 741GM UT WOS:000288852200017 PM 21422399 ER PT J AU Elia, N Sougrat, R Spurlin, TA Hurley, JH Lippincott-Schwartz, J AF Elia, Natalie Sougrat, Rachid Spurlin, Tighe A. Hurley, James H. Lippincott-Schwartz, Jennifer TI Dynamics of endosomal sorting complex required for transport (ESCRT) machinery during cytokinesis and its role in abscission SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE superresolution imaging; cell division; centrosomal protein of 55 kDa; mitotic kinesin-like protein 1; Madin-Darby canine kidney cells ID MEDIATED ABSCISSION; CELL-DIVISION; MIDBODY; PROTEIN; CEP55; CENTROSOME; MECHANISMS; SCISSION; SPASTIN; ARCHAEA AB The final stage of cytokinesis is abscission, the cutting of the narrow membrane bridge connecting two daughter cells. The endosomal sorting complex required for transport (ESCRT) machinery is required for cytokinesis, and ESCRT-III has membrane scission activity in vitro, but the role of ESCRTs in abscission has been undefined. Here, we use structured illumination microscopy and time-lapse imaging to dissect the behavior of ESCRTs during abscission. Our data reveal that the ESCRT-I subunit tumor-susceptibility gene 101 (TSG101) and the ESCRT-III subunit charged multivesicular body protein 4b (CHMP4B) are sequentially recruited to the center of the intercellular bridge, forming a series of cortical rings. Late in cytokinesis, however, CHMP4B is acutely recruited to the narrow constriction site where abscission occurs. The ESCRT disassembly factor vacuolar protein sorting 4 (VPS4) follows CHMP4B to this site, and cell separation occurs immediately. That arrival of ESCRT-III and VPS4 correlates both spatially and temporally with the abscission event suggests a direct role for these proteins in cytokinetic membrane abscission. C1 [Elia, Natalie; Sougrat, Rachid; Lippincott-Schwartz, Jennifer] Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. [Spurlin, Tighe A.] Natl Inst Stand & Technol, Gaithersburg, MD 20878 USA. [Hurley, James H.] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Lippincott-Schwartz, J (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. EM JLippin@helix.nih.gov RI Sanders, Susan/G-1957-2011; OI Sougrat, Rachid/0000-0001-6476-1886 FU National Institutes of Health, National Institute of Child Health and Human Development, National Institute of Diabetes and Digestive and Kidney Diseases; Intramural AIDS Targeted Antiviral Program FX We thank Misha Kozlov for mechanistic insights and fruitful discussion. We thank Carl Zeiss Microimaging, LLC for access to the ELYRA PS. 1 microscope and specifically thank Maya Everret for coordinating that access. We also thank Rainer Heintzmann for technical suggestions on SIM acquisition and reconstruction parameters, Mike Davidson for kindly proving the CAAX-tdEOS construct, and Phyllis Hanson for providing the CHMP4A polyclonal antibodies. We thank members of the J.L.-S. laboratory and Jeremy Swan, Angelika Rambold, and Nichole Jonas for help with the illustrations. This research was supported by the Intramural Program of the National Institutes of Health, National Institute of Child Health and Human Development, National Institute of Diabetes and Digestive and Kidney Diseases, and Intramural AIDS Targeted Antiviral Program. NR 29 TC 141 Z9 142 U1 3 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 MAR 22 PY 2011 VL 108 IS 12 BP 4846 EP 4851 DI 10.1073/pnas.1102714108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 739JC UT WOS:000288712200033 PM 21383202 ER PT J AU Gao, GJ Cheng, Y Wesolowska, N Rong, YKS AF Gao, Guanjun Cheng, Yan Wesolowska, Natalia Rong, Yikang S. TI Paternal imprint essential for the inheritance of telomere identity in Drosophila SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE evolution of new genes; telomere capping; epigenetic marker; chromatin condensation; spermatogenesis ID EFFECT GENE; MELANOGASTER; MAINTENANCE; GYNOGENESIS; SPERMATOZOA; CHROMATIN; PROTEIN; HOAP AB Chromatin remodeling during sperm maturation could erase epigenetic landmarks on the paternal genome, creating a challenge for its reestablishment on fertilization. Here, we show that selective retention of a chromosomal protein in mature sperm protects the identity of paternal telomeres in Drosophila. The ms (3) k81 (k81) gene is a duplication of hiphop that encodes a telomeric protein. Although HipHop protects telomeres in somatic cells, K81 is produced exclusively in males and localizes to telomeres in postmitotic cells, including mature sperm. In embryos fathered by k81 mutants, the maternal supplies fail to reestablish a protective cap on paternal telomeres, leading to their fusions. These fusions hinder the segregation of the paternal genome and result in haploid embryos with maternal chromosomes. The functional divergence between hiphop and k81 manifests not only in their expression patterns but also in the protein functions that they encode. By swapping the two coding regions, we show that K81 can replace HipHop for somatic protection; however, HipHop cannot replace K81 in the germ line to specify telomere identity, because HipHop ectopically expressed in the testis is removed from chromatin during sperm maturation. HipHop lacks a short motif in K81 that is essential for K81 to survive the remodeling process. We show that the combined functions of HipHop and K81 are likely fulfilled by the single ancestral hiphop locus in other Drosophila species, supporting the hypothesis that the evolutionary process of subfunctionalization was responsible for the preservation of the hiphop-k81 duplicate. C1 [Gao, Guanjun; Cheng, Yan; Wesolowska, Natalia; Rong, Yikang S.] NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Gao, Guanjun] Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China. RP Rong, YKS (reprint author), NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM rongy@mail.nih.gov RI rong, yikang/G-6179-2011 FU National Cancer Institute FX We thank Patrizia Morciano for her assistance in generating hiphop mutants and Sara Brinda for her assistance in generating the gfp-hoap allele. We thank Laboratory of Biochemistry and Molecular Biology members for their comments on the manuscript. The intramural program of the National Cancer Institute supported this research. NR 21 TC 18 Z9 18 U1 0 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 22 PY 2011 VL 108 IS 12 BP 4932 EP 4937 DI 10.1073/pnas.1016792108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 739JC UT WOS:000288712200048 PM 21383184 ER PT J AU Lu, JH Marjon, KD Marnell, LL Wang, RP Mold, C Du Clos, TW Sun, P AF Lu, Jinghua Marjon, Kristopher D. Marnell, Lorraine L. Wang, Ruipeng Mold, Carolyn Du Clos, Terry W. Sun, Peter TI Recognition and functional activation of the human IgA receptor (Fc alpha RI) by C-reactive protein SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE serum amyloid P component; CD89; acute phase protein ID AMYLOID-P COMPONENT; CRYSTAL-STRUCTURE; GAMMA RECEPTORS; MAST-CELLS; SERUM IGA; COMPLEX; RELEASE; KINASES; PHAGOCYTOSIS; INFLAMMATION AB C-reactive protein (CRP) is an important biomarker for inflammatory diseases. However, its role in inflammation beyond complement-mediated pathogen clearance remains poorly defined. We identified the major IgA receptor, Fc alpha RI, as a ligand for pentraxins. CRP recognized Fc alpha RI both in solution and on cells, and the pentraxin binding site on the receptor appears distinct from that recognized by IgA. Further competitive binding and mutational analysis showed that Fc alpha RI bound to the effector face of CRP in a region overlapping with complement C1q and Fc gamma receptor (Fc gamma R) binding sites. CRP cross-linking of Fc alpha RI resulted in extracellular signal-regulated kinase (ERK) phosphorylation, cytokine production, and degranulation in Fc alpha RI-transfected RBL cells. In neutrophils, CRP induced Fc alpha RI surface expression, phagocytosis, and TNF-alpha secretion. The ability of CRP to activate Fc alpha RI defines a function for pentraxins in inflammatory responses involving neutrophils and macrophages. It also highlights the innate aspect of otherwise humoral immunity-associated antibody receptors. C1 [Marjon, Kristopher D.; Marnell, Lorraine L.; Mold, Carolyn; Du Clos, Terry W.] Univ New Mexico, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA. [Lu, Jinghua; Wang, Ruipeng; Sun, Peter] NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Mold, Carolyn; Du Clos, Terry W.] Univ New Mexico, Dept Internal Med, Albuquerque, NM 87131 USA. [Marnell, Lorraine L.] Vet Affairs Med Ctr, Albuquerque, NM 87108 USA. RP Du Clos, TW (reprint author), Univ New Mexico, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA. EM tduclos@unm.edu; psun@nih.gov RI lu, jinghua/G-5872-2012; Wang, Ruipeng/I-1407-2013 OI Wang, Ruipeng/0000-0002-1003-1420 FU National Institute of Allergy and Infectious Diseases; National Research Service Award [F31AI080178]; National Institutes of Health [R21 AI085414]; Department of Veterans Affairs FX We thank Dr. Jeffrey Edberg for providing the Fc alpha RI-transfected G248 RBL cell line, Dr. Renato Monteiro for providing 9.4 RBL cells, and Dr. Barbara Bottazzi for providing the recombinant PTX3. Images were generated in the Cancer Center Fluorescence Microscope Shared Resource, University of New Mexico. This work was supported by intramural research funding from the National Institute of Allergy and Infectious Diseases, by National Research Service Award F31AI080178 (to K. D. M.), by National Institutes of Health Grant R21 AI085414, and by a Merit Review Award from the Department of Veterans Affairs. NR 34 TC 30 Z9 32 U1 1 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 22 PY 2011 VL 108 IS 12 BP 4974 EP 4979 DI 10.1073/pnas.1018369108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 739JC UT WOS:000288712200055 PM 21383176 ER PT J AU Yang, CZ Asthagiri, AR Iyer, RR Lu, J Xu, DS Ksendzovsky, A Brady, RO Zhuang, ZP Lonser, RR AF Yang, Chunzhang Asthagiri, Ashok R. Iyer, Rajiv R. Lu, Jie Xu, David S. Ksendzovsky, Alexander Brady, Roscoe O. Zhuang, Zhengping Lonser, Russell R. TI Missense mutations in the NF2 gene result in the quantitative loss of merlin protein and minimally affect protein intrinsic function SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TUMOR-SUPPRESSOR GENE; NEUROFIBROMATOSIS-2; MENINGIOMA; TUMORIGENESIS; DEGRADATION; PROTEASOME; EXPRESSION; ADHESION; CANCER AB Neurofibromatosis type 2 (NF2) is a multiple neoplasia syndrome and is caused by a mutation of the NF2 tumor suppressor gene that encodes for the tumor suppressor protein merlin. Biallelic NF2 gene inactivation results in the development of central nervous system tumors, including schwannomas, meningiomas, ependymomas, and astrocytomas. Although a wide variety of missense germline mutations in the coding sequences of the NF2 gene can cause loss of merlin function, the mechanism of this functional loss is unknown. To gain insight into the mechanisms underlying loss of merlin function in NF2, we investigated mutated merlin homeostasis and function in NF2-associated tumors and cell lines. Quantitative protein and RT-PCR analysis revealed that whereas merlin protein expression was significantly reduced in NF2-associated tumors, mRNA expression levels were unchanged. Transfection of genetic constructs of common NF2 missense mutations into NF2 gene-deficient meningioma cell lines revealed that merlin loss of function is due to a reduction in mutant protein half-life and increased protein degradation. Transfection analysis also demonstrated that recovery of tumor suppressor protein function is possible, indicating that these mutants maintain intrinsic functional capacity. Further, increased expression of mutant protein is possible after treatment with specific proteostasis regulators, implicating protein quality control systems in the degradative fate of mutant tumor suppressor proteins. These findings provide direct insight into protein function and tumorigenesis in NF2 and indicate a unique treatment paradigm for this disorder. C1 [Yang, Chunzhang; Asthagiri, Ashok R.; Iyer, Rajiv R.; Lu, Jie; Xu, David S.; Ksendzovsky, Alexander; Brady, Roscoe O.; Zhuang, Zhengping; Lonser, Russell R.] Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Brady, RO (reprint author), Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM bradyr@ninds.nih.gov; zhuangp@ninds.nih.gov; lonserr@ninds.nih.gov OI Xu, David/0000-0001-8987-4545 FU National Institute of Neurologic Disorders and Stroke at the National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute of Neurologic Disorders and Stroke at the National Institutes of Health. NR 25 TC 21 Z9 22 U1 2 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 22 PY 2011 VL 108 IS 12 BP 4980 EP 4985 DI 10.1073/pnas.1102198108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 739JC UT WOS:000288712200056 PM 21383154 ER PT J AU Verstraeten, VLRM Peckham, LA Olive, M Capell, BC Collins, FS Nabel, EG Young, SG Fong, LG Lammerding, J AF Verstraeten, Valerie L. R. M. Peckham, Lana A. Olive, Michelle Capell, Brian C. Collins, Francis S. Nabel, Elizabeth G. Young, Stephen G. Fong, Loren G. Lammerding, Jan TI Protein farnesylation inhibitors cause donut-shaped cell nuclei attributable to a centrosome separation defect SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cell division; nuclear envelope; doughnut-shaped nuclei; antitumor ID BIPOLAR SPINDLE FORMATION; FARNESYLTRANSFERASE INHIBITOR; MOUSE MODEL; CENP-F; DISEASE PHENOTYPES; PROGERIA-SYNDROME; PRELAMIN-A; LAMIN-A; ACCUMULATION; PERICENTRIN AB Despite the success of protein farnesyltransferase inhibitors (FTIs) in the treatment of certain malignancies, their mode of action is incompletely understood. Dissecting the molecular pathways affected by FTIs is important, particularly because this group of drugs is now being tested for the treatment of Hutchinson-Gilford progeria syndrome. In the current study, we show that FTI treatment causes a centrosome separation defect, leading to the formation of donut-shaped nuclei in nontransformed cell lines, tumor cell lines, and tissues of FTI-treated mice. Donut-shaped nuclei arise during chromatin decondensation in late mitosis; subsequently, cells with donut-shaped nuclei exhibit defects in karyokinesis, develop aneuploidy, and are often binucleated. Binucleated cells proliferate slowly. We identified lamin B1 and proteasome-mediated degradation of pericentrin as critical components in FTI-induced "donut formation" and binucleation. Reducing pericentrin expression or ectopic expression of nonfarnesylated lamin B1 was sufficient to elicit donut formation and binucleated cells, whereas blocking proteasomal degradation eliminated FTI-induced donut formation. Our studies have uncovered an important role of FTIs on centrosome separation and define pericentrin as a (indirect) target of FTIs affecting centrosome position and bipolar spindle formation, likely explaining some of the anticancer effects of these drugs. C1 [Verstraeten, Valerie L. R. M.; Peckham, Lana A.; Lammerding, Jan] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Cambridge, MA 02139 USA. [Verstraeten, Valerie L. R. M.; Peckham, Lana A.; Lammerding, Jan] Harvard Univ, Sch Med, Cambridge, MA 02139 USA. [Verstraeten, Valerie L. R. M.] Maastricht Univ, Med Ctr, Dept Dermatol, NL-6202 AZ Maastricht, Netherlands. [Verstraeten, Valerie L. R. M.] Maastricht Univ, Med Ctr, GROW Sch Oncol & Dev Biol, NL-6200 MD Maastricht, Netherlands. [Olive, Michelle; Nabel, Elizabeth G.] NHLBI, Bethesda, MD 20892 USA. [Capell, Brian C.; Collins, Francis S.; Nabel, Elizabeth G.] NHGRI, NIH, Bethesda, MD 20892 USA. [Young, Stephen G.; Fong, Loren G.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. RP Lammerding, J (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Cambridge, MA 02139 USA. EM jlammerding@rics.bwh.harvard.edu RI Lammerding, Jan/A-9498-2016; OI Lammerding, Jan/0000-0003-4335-8611; Capell, Brian/0000-0002-7036-8359 FU National Institutes of Health [HL082792, NS059348, AG035626, HL086683, HL089781]; Ellison Medical Foundation; Progeria Research Foundation; Netherlands Genomics Initiative [2007/01129/MW]; American Heart Association [09POST2080264] FX We thank the following investigators for providing reagents: Dr. A. Ishov, Dr. D. Bader, Dr. C. Stewart, Dr. F. Gertler, Dr. T. Glover, Dr. P. Adams, Dr. R. Goldman, Dr. T. Yen, Dr. D. Cleveland, Dr. K. Roux, and Dr. I. Raska. We thank the following investigators for helpful discussions: Dr. K. Roux and Dr. R. Prince. This work was supported by National Institutes of Health Grants HL082792, NS059348, AG035626, HL086683, and HL089781; the Ellison Medical Foundation Senior Scholar Program; the Progeria Research Foundation; and fellowships from the Netherlands Genomics Initiative 2007/01129/MW (to V.L.R.M.V.) and the American Heart Association 09POST2080264 (to V.L.R.M.V.). NR 35 TC 30 Z9 31 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 22 PY 2011 VL 108 IS 12 BP 4997 EP 5002 DI 10.1073/pnas.1019532108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 739JC UT WOS:000288712200059 PM 21383178 ER PT J AU Bolton, EE Kim, S Bryant, SH AF Bolton, Evan E. Kim, Sunghwan Bryant, Stephen H. TI PubChem3D: Diversity of shape SO JOURNAL OF CHEMINFORMATICS LA English DT Article ID GAUSSIAN DESCRIPTION; MOLECULAR SHAPE; DOCKING; INFORMATION AB Background: The shape diversity of 16.4 million biologically relevant molecules from the PubChem Compound database and their 1.46 billion diverse conformers was explored as a function of molecular volume. Results: The diversity of shape space was investigated by determining the shape similarity threshold to achieve a maximum on the count of reference shapes per unit of conformer volume. The rate of growth in shape space, as represented by a decreasing shape similarity threshold, was found to be remarkably smooth as a function of volume. There was no apparent correlation between the count of conformers per unit volume and their diversity, meaning that a single reference shape can describe the shape space of many chemical structures. The ability of a volume to describe the shape space of lesser volumes was also examined. It was shown that a given volume was able to describe 40-70% of the shape diversity of lesser volumes, for the majority of the volume range considered in this study. Conclusion: The relative growth of shape diversity as a function of volume and shape similarity is surprisingly uniform. Given the distribution of chemicals in PubChem versus what is theoretically synthetically possible, the results from this analysis should be considered a conservative estimate to the true diversity of shape space. C1 [Bolton, Evan E.; Kim, Sunghwan; Bryant, Stephen H.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Dept Hlth & Human Serv, Bethesda, MD 20894 USA. RP Bolton, EE (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Dept Hlth & Human Serv, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM bolton@ncbi.nlm.nih.gov RI Kim, Sunghwan/A-6738-2008 OI Kim, Sunghwan/0000-0001-9828-2074 FU National Library of Medicine, National Institutes of Health, U. S. Department of Health and Human Services FX We are grateful to the NCBI Systems staff, especially Ron Patterson, Charlie Cook, and Don Preuss, whose efforts helped make the PubChem3D project possible. This research was supported in part by the Intramural Research Program of the National Library of Medicine, National Institutes of Health, U. S. Department of Health and Human Services. This study utilized the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health, Bethesda, MD. http://biowulf.nih.gov. NR 20 TC 12 Z9 12 U1 1 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1758-2946 J9 J CHEMINFORMATICS JI J. Cheminformatics PD MAR 21 PY 2011 VL 3 AR 9 DI 10.1186/1758-2946-3-9 PG 14 WC Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA 891NZ UT WOS:000300225200001 PM 21418625 ER PT J AU Huang, BX Akbar, M Kevala, K Kim, HY AF Huang, Bill X. Akbar, Mohammed Kevala, Karl Kim, Hee-Yong TI Phosphatidylserine is a critical modulator for Akt activation SO JOURNAL OF CELL BIOLOGY LA English DT Article ID PROTEIN-KINASE-B; PLECKSTRIN HOMOLOGY DOMAIN; HAMSTER OVARY CELLS; SMALL UNILAMELLAR VESICLES; CHEMICAL CROSS-LINKING; FATTY-ACID-BINDING; DOCOSAHEXAENOIC ACID; ELECTROSTATIC INTERACTIONS; MASS-SPECTROMETRY; SERUM-ALBUMIN AB Akt activation relies on the binding of Akt to phosphatidylinositol-3,4,5-trisphosphate (PIP(3)) in the membrane. Here, we demonstrate that Akt activation requires not only PIP3 but also membrane phosphatidylserine (PS). The extent of insulin-like growth factor-induced Akt activation and downstream signaling as well as cell survival under serum starvation conditions positively correlates with plasma membrane PS levels in living cells. PS promotes Akt-PIP(3) binding, participates in PIP(3)-induced Akt interdomain conformational changes for T308 phosphorylation, and causes an open conformation that allows for S473 phosphorylation by mTORC2. PS interacts with specific residues in the pleckstrin homology (PH) and regulatory (RD) domains of Akt. Disruption of PS-Akt interaction by mutation impairs Akt signaling and increases susceptibility to cell death. These data identify a critical function of PS for Akt activation and cell survival, particularly in conditions with limited PIP3 availability. The novel molecular interaction mechanism for Akt activation suggests potential new targets for controlling Akt-dependent cell survival and proliferation. C1 [Huang, Bill X.; Akbar, Mohammed; Kevala, Karl; Kim, Hee-Yong] NIAAA, Mol Signalling Lab, NIH, Bethesda, MD 20892 USA. RP Kim, HY (reprint author), NIAAA, Mol Signalling Lab, NIH, Bethesda, MD 20892 USA. EM hykim@nih.gov FU National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health. NR 58 TC 52 Z9 53 U1 4 U2 14 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD MAR 21 PY 2011 VL 192 IS 6 BP 979 EP 992 DI 10.1083/jcb.201005100 PG 14 WC Cell Biology SC Cell Biology GA 743AD UT WOS:000288986200010 PM 21402788 ER PT J AU Greer, YE Rubin, JS AF Greer, Yoshimi Endo Rubin, Jeffrey S. TI Casein kinase 1 delta functions at the centrosome to mediate Wnt-3a-dependent neurite outgrowth SO JOURNAL OF CELL BIOLOGY LA English DT Article ID MAMMALIAN CIRCADIAN CLOCK; BETA-CATENIN; DISHEVELLED PHOSPHORYLATION; AXON GUIDANCE; I-EPSILON; SCAFFOLDING PROTEIN; LOCALIZATION; PATHWAY; CELLS; DIFFERENTIATION AB Previously we determined that Dishevelled-2/3 (Dvl) mediate Wnt-3a-dependent neurite outgrowth in Ewing sarcoma family tumor cells. Here we report that neurite extension was associated with Dvl phosphorylation and that both were inhibited by the casein kinase 1 (CK1) delta/epsilon inhibitor IC261. Small interfering RNAs targeting either CK1 delta or CK1 epsilon decreased Dvl phosphorylation, but only knockdown of CK1 delta blocked neurite outgrowth. CK1 delta but not CK1 epsilon was detected at the centrosome, an organelle associated with neurite formation. Deletion analysis mapped the centrosomal localization signal (CLS) of CK1 delta to its C-terminal domain. A fusion protein containing the CLS and EGFP displaced full-length CK1 delta from the centrosome and inhibited Wnt-3a-dependent neurite outgrowth. In contrast to wild-type CK1 epsilon, a chimera comprised of the kinase domain of CK1 epsilon and the CLS of CK1 delta localized to the centrosome and rescued Wnt-3a-dependent neurite outgrowth suppressed by CK1 delta knockdown. These results provide strong evidence that the centrosomal localization of CK1 delta is required for Wnt-3a-dependent neuritogenesis. C1 [Greer, Yoshimi Endo; Rubin, Jeffrey S.] NCI, Lab Cellular & Mol Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Rubin, JS (reprint author), NCI, Lab Cellular & Mol Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM rubinj@mail.nih.gov FU National Institutes of Health, National Cancer Institute FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. NR 57 TC 21 Z9 25 U1 1 U2 6 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD MAR 21 PY 2011 VL 192 IS 6 BP 993 EP 1004 DI 10.1083/jcb.201011111 PG 12 WC Cell Biology SC Cell Biology GA 743AD UT WOS:000288986200011 PM 21422228 ER PT J AU Strbo, N Vaccari, M Pahwa, S Kolber, MA Fisher, E Gonzalez, L Doster, MN Hryniewicz, A Felber, BK Pavlakis, GN Franchini, G Podack, ER AF Strbo, Natasa Vaccari, Monica Pahwa, Savita Kolber, Michael A. Fisher, Eva Gonzalez, Louis Doster, Melvin N. Hryniewicz, Anna Felber, Barbara K. Pavlakis, George N. Franchini, Genoveffa Podack, Eckhard R. TI Gp96(SIV)Ig immunization induces potent polyepitope specific, multifunctional memory responses in rectal and vaginal mucosa SO VACCINE LA English DT Article DE gp96-chaperone; Mucosa; Non-human primate; Rectum; Vagina ID HEAT-SHOCK PROTEINS; CYTOTOXIC T-LYMPHOCYTES; DENDRITIC CELLS; ANTIGEN PRESENTATION; PROTECTIVE IMMUNITY; CROSS-PRESENTATION; CUTTING EDGE; REJECTION; RECEPTOR; VACCINE AB The ER-resident chaperone gp96, when released by cell lysis, induces an immunogenic chemokine signature and causes innate immune activation of DC and NK cells. Here we show that intraperitoneal immunization with a genetically engineered, secreted form of gp96, gp96-Ig chaperoning SIV antigens, induces high levels of antigen specific CD8 CTL in the rectal and vaginal mucosa of Rhesus macaques. The frequency of SIV Gag- and SIV Tat-tetramer positive CD8 CTL in the intestinal mucosa reached 30-50% after the third immunization. Tetramer positive CD8 CTL expressed appropriate functional (granzyme B) and migration markers (CD103). The polyepitope specificity of the mucosal CD8 and CD4 response is evident from a strong, multifunctional cytokine response upon stimulation with peptides covering the gag, tat and env proteins. Induction of powerful mucosal effector CD8 CTL, responses by cell-based gp96(SIV)-Ig immunization may provide a pathway to the development of safe and effective SIV/HIV vaccines. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Strbo, Natasa; Pahwa, Savita; Fisher, Eva; Gonzalez, Louis; Podack, Eckhard R.] Univ Miami, Miller Sch Med, Dept Microbiol & Immunol, Miami, FL 33136 USA. [Strbo, Natasa; Pahwa, Savita; Kolber, Michael A.; Gonzalez, Louis; Podack, Eckhard R.] Univ Miami, Miller Sch Med, Ctr AIDS Res, Miami, FL 33136 USA. [Vaccari, Monica; Doster, Melvin N.; Hryniewicz, Anna; Franchini, Genoveffa] NCI, Anim Models & Retroviral Vaccines Sect, NIH, Bethesda, MD 20892 USA. [Kolber, Michael A.] Univ Miami, Miller Sch Med, Dept Med, Miami, FL 33136 USA. [Felber, Barbara K.] NCI, Human Retrovirus Pathogenesis Sect, Frederick, MD 21702 USA. [Pavlakis, George N.] NCI, Human Retrovirus Sect, Frederick, MD 21702 USA. RP Podack, ER (reprint author), 1600 NW 10th Ave,RMSB 3045, Miami, FL 33136 USA. EM epodack@med.miami.edu FU Public Health Service [R21 AIO68515, R21/R33 AI073234, CA109094]; ACGT (Alliance for Cancer Gene Therapy), Developmental Center for AIDS Research (DCFAR) University of Miami; NIH, National Cancer Institute, Center for Cancer Research FX This research was supported by Public Health Service Grants R21 AIO68515, R21/R33 AI073234, CA109094, by a Grant from ACGT (Alliance for Cancer Gene Therapy), Developmental Center for AIDS Research (DCFAR) University of Miami and by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 37 TC 11 Z9 11 U1 1 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAR 21 PY 2011 VL 29 IS 14 BP 2619 EP 2625 DI 10.1016/j.vaccine.2011.01.044 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 745CD UT WOS:000289140600017 PM 21277409 ER PT J AU Hassan, SA AF Hassan, Sergio A. TI Microscopic mechanism of nanocrystal formation from solution by cluster aggregation and coalescence SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID LENNARD-JONES SYSTEM; CRYSTAL NUCLEATION; MOLECULAR-DYNAMICS; COMPUTER-SIMULATION; ORIENTED ATTACHMENT; AQUEOUS-SOLUTIONS; CRYSTALLIZATION; BIOMINERALIZATION; POTENTIALS; NUCLEUS AB Solute-cluster aggregation and particle fusion have recently been suggested as alternative routes to the classical mechanism of nucleation from solution. The role of both processes in the crystallization of an aqueous electrolyte under controlled salt addition is here elucidated by molecular dynamics simulation. The time scale of the simulation allows direct observation of the entire crystallization pathway, from early events in the prenucleation stage to the formation of a nanocrystal in equilibrium with concentrated solution. The precursor originates in a small amorphous aggregate stabilized by hydration forces. The core of the nucleus becomes crystalline over time and grows by coalescence of the amorphous phase deposited at the surface. Imperfections of ion packing during coalescence promote growth of two conjoint crystallites. A parameter of order and calculated cohesive energies reflect the increasing crystalline order and stress relief at the grain boundary. Cluster aggregation plays a major role both in the formation of the nucleus and in the early stages of postnucleation growth. The mechanism identified shares common features with nucleation of solids from the melt and of liquid droplets from the vapor. [doi: 10.1063/1.3560637] C1 NIH, Ctr Mol Modeling, DCB CIT, US DHHS, Bethesda, MD 20892 USA. RP Hassan, SA (reprint author), NIH, Ctr Mol Modeling, DCB CIT, US DHHS, Bldg 10, Bethesda, MD 20892 USA. EM hassan@mail.nih.gov FU National of Institutes of Health (NIH) FX This study was supported by the National of Institutes of Health (NIH) Intramural Research Program and utilized the high-performance computer capabilities of the Biowulf Linux cluster at the NIH. The author thanks Toshiko Ichiye for discussions. NR 38 TC 13 Z9 13 U1 4 U2 35 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 J9 J CHEM PHYS JI J. Chem. Phys. PD MAR 21 PY 2011 VL 134 IS 11 AR 114508 DI 10.1063/1.3560637 PG 7 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 737VQ UT WOS:000288597700033 PM 21428633 ER PT J AU Jo, J Fortin, JY Choi, MY AF Jo, Junghyo Fortin, Jean-Yves Choi, M. Y. TI Weibull-type limiting distribution for replicative systems SO PHYSICAL REVIEW E LA English DT Article ID STATISTICS AB The Weibull function is widely used to describe skew distributions observed in nature. However, the origin of this ubiquity is not always obvious to explain. In the present paper, we consider the well-known Galton-Watson branching process describing simple replicative systems. The shape of the resulting distribution, about which little has been known, is found essentially indistinguishable from the Weibull form in a wide range of the branching parameter; this can be seen from the exact series expansion for the cumulative distribution, which takes a universal form. We also find that the branching process can be mapped into a process of aggregation of clusters. In the branching and aggregation process, the number of events considered for branching and aggregation grows cumulatively in time, whereas, for the binomial distribution, an independent event occurs at each time with a given success probability. C1 [Jo, Junghyo] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. [Fortin, Jean-Yves] Nancy Univ, CNRS, Inst Jean Lamour, Grp Phys Stat,Dept Phys Matiere & Mat, F-54506 Vandoeuvre Les Nancy, France. [Choi, M. Y.] Seoul Natl Univ, Ctr Theoret Phys, Dept Phys & Astron, Seoul 151747, South Korea. RP Jo, J (reprint author), NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. RI Jo, Junghyo/D-4889-2011; OI Choi, MooYoung/0000-0001-8070-7716; Fortin, Jean-Yves/0000-0002-3527-869X FU NIH, NIDDK; NRF [2009-0080791] FX One of us (M.Y.C.) thanks the Departement de Physique de la Matiere et des Materiaux, Institut Jean Lamour, at Universite Henri Poincare, where part of this work was carried out, for hospitality during his stay. This work was supported by the intramural research program of the NIH, NIDDK (J.J.), and by the NRF through the Basic Science Research Program (Grant No. 2009-0080791) (M.Y.C.). NR 18 TC 9 Z9 9 U1 0 U2 1 PU AMER PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1539-3755 J9 PHYS REV E JI Phys. Rev. E PD MAR 21 PY 2011 VL 83 IS 3 AR 031123 DI 10.1103/PhysRevE.83.031123 PN 1 PG 6 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA 737VU UT WOS:000288598200001 PM 21517470 ER PT J AU Hong, S Hikosaka, O AF Hong, Simon Hikosaka, Okihide TI Dopamine-mediated learning and switching in cortico-striatal circuit explain behavioral changes in reinforcement learning SO FRONTIERS IN BEHAVIORAL NEUROSCIENCE LA English DT Article DE LTP; LTD; model; saccade; latency; reaction time; reward; motivation AB The basal ganglia are thought to play a crucial role in reinforcement learning. Central to the learning mechanism are dopamine (DA) D1 and D2 receptors located in the cortico-striatal synapses. However, it is still unclear how this DA-mediated synaptic plasticity is deployed and coordinated during reward-contingent behavioral changes. Here we propose a computational model of reinforcement learning that uses different thresholds of D1- and D2-mediated synaptic plasticity which are antagonized by DA-independent synaptic plasticity. A phasic increase in DA release caused by a larger-than-expected reward induces long-term potentiation (LTP) in the direct pathway, whereas a phasic decrease in DA release caused by a smaller-than-expected reward induces a cessation of long-term depression, leading to LTP in the indirect pathway. This learning mechanism can explain the robust behavioral adaptation observed in a location-reward-value-association task where the animal makes shorter latency saccades to reward locations. The changes in saccade latency become quicker as the monkey becomes more experienced. This behavior can be explained by a switching mechanism which activates the cortico-striatal circuit selectively. Our model also shows how D1- or D2-receptor blocking experiments affect selectively either reward or no-reward trials. The proposed mechanisms also explain the behavioral changes in Parkinson's disease. C1 [Hong, Simon; Hikosaka, Okihide] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Hong, S (reprint author), NEI, Sensorimotor Res Lab, NIH, 49 Convent Dr, Bethesda, MD 20892 USA. EM hongy@nei.nih.gov FU National Eye Institute FX We are grateful to M. Isoda, L. Ding for providing data (monkey T and D, respectively), C. R. Hansen, E. S. Bromberg-Martin for helpful comments. This work was supported by the intramural research program of the National Eye Institute. NR 79 TC 21 Z9 21 U1 3 U2 10 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 MAR 21 PY 2011 VL 5 AR 15 DI 10.3389/fnbeh.2011.00015 PG 17 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA V29VU UT WOS:000208776700001 PM 21472026 ER PT J AU Kirschbaum, M Frankel, P Popplewell, L Zain, J Delioukina, M Pullarkat, V Matsuoka, D Pulone, B Rotter, AJ Espinoza-Delgado, I Nademanee, A Forman, SJ Gandara, D Newman, E AF Kirschbaum, Mark Frankel, Paul Popplewell, Leslie Zain, Jasmine Delioukina, Maria Pullarkat, Vinod Matsuoka, Deron Pulone, Bernadette Rotter, Arnold J. Espinoza-Delgado, Igor Nademanee, Auayporn Forman, Stephen J. Gandara, David Newman, Edward TI Phase II Study of Vorinostat for Treatment of Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma and Mantle Cell Lymphoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HISTONE DEACETYLASE INHIBITOR; LOW-GRADE; FOLLICULAR LYMPHOMA; RESPONSE CRITERIA; LEUKEMIA CELLS; FOLLOW-UP; TRANSPLANTATION; EXPRESSION; RITUXIMAB; BENDAMUSTINE AB Purpose We performed a phase II study of oral vorinostat, a histone and protein deacetylase inhibitor, to examine its efficacy and tolerability in patients with relapsed/refractory indolent lymphoma. Patients and Methods In this open label phase II study (NCT00253630), patients with relapsed/refractory follicular lymphoma (FL), marginal zone lymphoma (MZL), or mantle cell lymphoma (MCL), with <= 4 prior therapies were eligible. Oral vorinostat was administered at a dose of 200 mg twice daily on days 1 through 14 of a 21-day cycle until progression or unacceptable toxicity. The primary end point was objective response rate (ORR), with secondary end points of progression-free survival (PFS), time to progression, duration of response, safety, and tolerability. Results All 35 eligible patients were evaluable for response. The median number of vorinostat cycles received was nine. ORR was 29% (five complete responses [CR] and five partial responses [ PR]). For 17 patients with FL, ORR was 47% (four CR, four PR). There were two of nine responders with MZL (one CR, one PR), and no formal responders among the nine patients with MCL, although one patient maintained stable disease for 26 months. Median PFS was 15.6 months for patients with FL, 5.9 months for MCL, and 18.8 months for MZL. The drug was well-tolerated over long periods of treatment, with the most common grade 3 adverse events being thrombocytopenia, anemia, leucopenia, and fatigue. Conclusion Oral vorinostat is a promising agent in FL and MZL, with an acceptable safety profile. Further studies in combination with other active agents in this setting are warranted. J Clin Oncol 29:1198-1203. (C) 2011 by American Society of Clinical Oncology C1 City Hope Natl Med Ctr, Duarte, CA USA. Univ Calif Davis, Davis, CA 95616 USA. NYU, Med Ctr, New York, NY 10016 USA. NCI, Canc Therapy Evaluat Program, Rockville, MD USA. RP Kirschbaum, M (reprint author), Nevada Canc Inst, 1 Breakthrough Way, Las Vegas, NV 89135 USA. EM mkirschbaum@nvcancer.org FU National Cancer Institute Cancer Therapy Evaluation [U01-CA-62505, N01-CM-62209]; City of Hope [P30-CA-033572] FX Supported by Grants No. U01-CA-62505 and N01-CM-62209 from the National Cancer Institute Cancer Therapy Evaluation Program and Grant No. P30-CA-033572 from the City of Hope. NR 28 TC 94 Z9 95 U1 1 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 20 PY 2011 VL 29 IS 9 BP 1198 EP 1203 DI 10.1200/JCO.2010.32.1398 PG 6 WC Oncology SC Oncology GA 736YZ UT WOS:000288532500034 PM 21300924 ER PT J AU Gray, TR Dams, R Choo, RE Jones, HE Huestis, MA AF Gray, Teresa R. Dams, Riet Choo, Robin E. Jones, Hendree E. Huestis, Marilyn A. TI Methadone disposition in oral fluid during pharmacotherapy for opioid-dependence SO FORENSIC SCIENCE INTERNATIONAL LA English DT Article DE Methadone; Oral fluid; Opioid-dependence; Saliva ID MAINTENANCE TREATMENT; LIQUID-CHROMATOGRAPHY; ILLICIT DRUGS; BUPRENORPHINE; PREVALENCE; SALIVA; PHARMACOKINETICS; IMPAIRMENT; COLLECTION; METABOLITE AB Introduction: Oral fluid testing is widely used for detecting drug exposure, but data describing methadone and metabolites in oral fluid during pharmacotherapy for opioid-dependence are relatively limited. Methods: 414 oral fluid specimens from 16 opioid-dependent pregnant women receiving daily methadone were analyzed for methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), and methadol by liquid chromatography-mass spectrometry. Results: All oral fluid specimens contained methadone greater than 1 ng/mL; 88% were positive for EDDP and 12% for methadol. Over 95% of oral fluid specimens exceeded the 20 ng/mL methadone cutoff set by the European Driving Under the Influence of Drugs, Alcohol and Medicines (DRUID) study. Methadone and EDDP oral fluid concentrations were highly variable within and between participants, did not predict methadone dose, but were negatively correlated with pH. Conclusion: Methadone was readily identified in oral fluid at concentrations greater than 20 ng/mL following daily 30-110 mg/day methadone pharmacotherapy. As no specimens contained only EDDP or methadol, there was no advantage to including these analytes for identification of methadone exposure. As nearly all oral fluid specimens from methadone-maintained patients exceeded the DRUID guideline, the 20 ng/mL cutoff appears to be sensitive enough to detect daily methadone exposure; however, additional indicators of behavioral and/or motor impairment would be necessary to provide evidence of driving impairment. Published by Elsevier Ireland Ltd. C1 [Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Jones, Hendree E.] Johns Hopkins Sch Med, Baltimore, MD 21224 USA. RP Huestis, MA (reprint author), NIDA, Intramural Res Program, NIH, 251 Bayview Blvd,Suite 200,Room 05A721, Baltimore, MD 21224 USA. EM teresa.r.gray@gmail.com; riet.2.dams@gsk.com; rec27@pitt.edu; hejones@jhmi.edu; mhuestis@intra.nida.nih.gov FU National Institute on Drug Abuse, National Institutes of Health [DA12403] FX This research was funded by the Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health and Extramural Grant DA12403. NR 31 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0379-0738 J9 FORENSIC SCI INT JI Forensic Sci.Int. PD MAR 20 PY 2011 VL 206 IS 1-3 BP 98 EP 102 DI 10.1016/j.forsciint.2010.06.031 PG 5 WC Medicine, Legal SC Legal Medicine GA 732PO UT WOS:000288200400041 PM 20667673 ER PT J AU Dulcey, AE Qasba, PK Lamb, J Griffiths, GL AF Dulcey, Andres E. Qasba, Pradman K. Lamb, Jeffrey Griffiths, Gary L. TI Improved synthesis of UDP-2-(2-ketopropyl)galactose and a first synthesis of UDP-2-(2-ketopropyl)glucose for the site-specific linking of biomolecules via modified glycan residues using glycosyltransferases SO TETRAHEDRON LA English DT Article DE Carbohydrate chemistry; Organic synthesis; Modified sugars; Glycosyltransferases AB The potential of wild-type and mutant glycosyltransferases to produce glycoconjugates carrying sugar moieties with chemical handles has made it possible to conjugate biomelecules with orthogonal reacting groups at specific sites. The synthesis of UDP-2-(2-ketopropyl)galactose has been previously carried out, albeit with difficulty and low efficiency. A modified approach has been developed for the synthesis of UDP-2-(2-ketopropyl)glucose and UDP-2-(2-ketopropyl)galactose, allowing better access to the desired test compounds, the UDP-2-(2-ketopropyl)glucose and UDP-2-(2-ketopropyl)galactose analogs were synthesized in eight steps and 4.8% and 5.3% overall yield, respectively, an improvement over the first generation synthesis involving eight steps and an overall yield of 0.7%. Published by Elsevier Ltd. C1 [Dulcey, Andres E.; Lamb, Jeffrey; Griffiths, Gary L.] NHLBI, Imaging Probe Dev Ctr, NIH, Rockville, MD 20850 USA. [Qasba, Pradman K.] NCI, Struct Glycobiol Sect, Nanobiol Program, Ctr Canc Res, Frederick, MD 21702 USA. RP Dulcey, AE (reprint author), NHLBI, Imaging Probe Dev Ctr, NIH, 9800 Med Ctr Dr, Rockville, MD 20850 USA. EM dulceyan@mail.nih.gov FU NIH Roadmap for Medical Research Initiative FX This work was supported by the NIH Roadmap for Medical Research Initiative through its establishment of the Imaging Probe Development Center, administered by the National Heart, Lung, and Blood Institute. NR 11 TC 6 Z9 6 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4020 J9 TETRAHEDRON JI Tetrahedron PD MAR 18 PY 2011 VL 67 IS 11 BP 2013 EP 2017 DI 10.1016/j.tet.2011.01.081 PG 5 WC Chemistry, Organic SC Chemistry GA 796FN UT WOS:000293037300002 PM 21436962 ER PT J AU McNeill, DS Sheely, CJ Ecker, JL Badea, TC Morhardt, D Guido, W Hattar, S AF McNeill, David S. Sheely, Catherine J. Ecker, Jennifer L. Badea, Tudor C. Morhardt, Duncan Guido, William Hattar, Samer TI Development of melanopsin-based irradiance detecting circuitry SO NEURAL DEVELOPMENT LA English DT Article ID RETINAL GANGLION-CELLS; HYPOTHALAMIC SUPRACHIASMATIC NUCLEUS; OLIVARY PRETECTAL NUCLEUS; PUPILLARY LIGHT REFLEX; RETINOHYPOTHALAMIC TRACT; POSTNATAL-DEVELOPMENT; CIRCADIAN-RHYTHMS; MOUSE; RAT; PROJECTIONS AB Background: Most retinal ganglion cells (RGCs) convey contrast and motion information to visual brain centers. Approximately 2% of RGCs are intrinsically photosensitive (ipRGCs), express melanopsin and are necessary for light to modulate specific physiological processes in mice. The ipRGCs directly target the suprachiasmatic nucleus (SCN) to photoentrain circadian rhythms, and the olivary pretectal nucleus (OPN) to mediate the pupillary light response. How and when this ipRGC circuitry develops is unknown. Results: Here, we show that some ipRGCs follow a delayed developmental time course relative to other image-forming RGCs. Specifically, ipRGC neurogenesis extends beyond that of other RGCs, and ipRGCs begin innervating the SCN at postnatal ages, unlike most RGCs, which innervate their image-forming targets embryonically. Moreover, the appearance of ipRGC axons in the OPN coincides precisely with the onset of the pupillary light response. Conclusions: Some ipRGCs differ not only functionally but also developmentally from RGCs that mediate pattern-forming vision. C1 [Morhardt, Duncan; Guido, William] Virginia Commonwealth Univ, Dept Anat & Neurobiol, Richmond, VA 23298 USA. [McNeill, David S.; Sheely, Catherine J.; Ecker, Jennifer L.; Hattar, Samer] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. [Badea, Tudor C.] NEI, Retinal Circuit Dev & Genet Unit, N NRL, NIH, Bethesda, MD 20892 USA. RP Guido, W (reprint author), Virginia Commonwealth Univ, Dept Anat & Neurobiol, Med Coll Virginia Campus, Richmond, VA 23298 USA. EM wguido@vcu.edu; shattar@jhu.edu FU Johns Hopkins University Mouse Tri-Lab; NIH [GM076430, NIH EY012716]; David and Lucille Packard Foundation; Alfred P Sloan Foundation FX Aaron Stephan and Drs Andy Huberman, Alex Bortvin, Marnie Halpern, Rejji Kuruvilla and Haiqing Zhao for suggestions and proofreading the manuscript, Tara LeGates for help with statistics, and the Johns Hopkins University Mouse Tri-Lab for support. This research was funded by NIH GM076430, NIH EY012716, the David and Lucille Packard Foundation, and the Alfred P Sloan Foundation. NR 37 TC 33 Z9 34 U1 2 U2 13 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1749-8104 J9 NEURAL DEV JI Neural Dev. PD MAR 18 PY 2011 VL 6 AR 8 DI 10.1186/1749-8104-6-8 PG 10 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 763BY UT WOS:000290529400001 PM 21418557 ER PT J AU Rothenburg, S Chinchar, VG Dever, TE AF Rothenburg, Stefan Chinchar, V. Gregory Dever, Thomas E. TI Characterization of a ranavirus inhibitor of the antiviral protein kinase PKR SO BMC MICROBIOLOGY LA English DT Article ID DOUBLE-STRANDED-RNA; INITIATION FACTOR-II; DNA BINDING DOMAINS; FAMILY-IRIDOVIRIDAE; SUBSTRATE RECOGNITION; TRANSLATIONAL CONTROL; EUKARYOTIC INITIATION-FACTOR-2-ALPHA; GROUPER IRIDOVIRUS; MOLECULAR-CLONING; CRYSTAL-STRUCTURE AB Background: Ranaviruses (family Iridoviridae) are important pathogens of lower vertebrates. However, little is known about how they circumvent the immune response of their hosts. Many ranaviruses contain a predicted protein, designated vIF2 alpha, which shows homology with the eukaryotic translation initiation factor 2 alpha. In analogy to distantly related proteins found in poxviruses vIF2 alpha might act as an inhibitor of the antiviral protein kinase PKR. Results: We have characterized the function of vIF2a from Rana catesbeiana virus Z (RCV-Z). Multiple sequence alignments and secondary structure prediction revealed homology of vIF2a with eIF2 alpha throughout the S1-, helical- and C-terminal domains. Genetic and biochemical analyses showed that vIF2 alpha blocked the toxic effects of human and zebrafish PKR in a heterologous yeast system. Rather than complementing eIF2 alpha function, vIF2a acted in a manner comparable to the vaccinia virus (VACV) K3L protein (K3), a pseudosubstrate inhibitor of PKR. Both vIF2 alpha and K3 inhibited human PKR-mediated eIF2 alpha phosphorylation, but not PKR autophosphorylation on Thr446. In contrast the E3L protein ( E3), another poxvirus inhibitor of PKR, inhibited both Thr446 and eIF2 alpha Ser51 phosphorylation. Interestingly, phosphorylation of eIF2 alpha by zebrafish PKR was inhibited by vIF2 alpha and E3, but not by K3. Effective inhibition of PKR activity coincided with increased PKR expression levels, indicative of relieved autoinhibition of PKR expression. Experiments with vIF2 alpha deletion constructs, showed that both the N-terminal and helical domains were sufficient for inhibition of PKR, whereas the C-terminal domain was dispensable. Conclusions: Our results show that RCV-Z vIF2 alpha is a functional inhibitor of human and zebrafish PKR, and probably functions in similar fashion as VACV K3. This constitutes an important step in understanding the interaction of ranaviruses and the host innate immune system. C1 [Rothenburg, Stefan; Dever, Thomas E.] NICHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. [Rothenburg, Stefan] Kansas State Univ, Div Biol, Manhattan, KS 66506 USA. [Chinchar, V. Gregory] Univ Mississippi, Med Ctr, Dept Microbiol, Jackson, MS 39216 USA. RP Rothenburg, S (reprint author), NICHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. EM sr1hsv@ksu.edu RI Rothenburg, Stefan/A-8340-2008; OI Dever, Thomas/0000-0001-7120-9678 FU National Institutes of Health, NICHD FX We thank Alan Hinnebusch and members of the Dever and Hinnebusch labs for helpful discussions and Tom Donahue for yeast strains. This work was supported in part by the Intramural Research Program of the National Institutes of Health, NICHD. NR 55 TC 22 Z9 22 U1 0 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2180 J9 BMC MICROBIOL JI BMC Microbiol. PD MAR 18 PY 2011 VL 11 AR 56 DI 10.1186/1471-2180-11-56 PG 12 WC Microbiology SC Microbiology GA 743BR UT WOS:000288991100001 PM 21418572 ER PT J AU Mollapour, M Tsutsumi, S Truman, AW Xu, WP Vaughan, CK Beebe, K Konstantinova, A Vourganti, S Panaretou, B Piper, PW Trepel, JB Prodromou, C Pearl, LH Neckers, L AF Mollapour, Mehdi Tsutsumi, Shinji Truman, Andrew W. Xu, Wanping Vaughan, Cara K. Beebe, Kristin Konstantinova, Anna Vourganti, Srinivas Panaretou, Barry Piper, Peter W. Trepel, Jane B. Prodromou, Chrisostomos Pearl, Laurence H. Neckers, Len TI Threonine 22 Phosphorylation Attenuates Hsp90 Interaction with Cochaperones and Affects Its Chaperone Activity SO MOLECULAR CELL LA English DT Article ID HEAT-SHOCK-PROTEIN; CASEIN KINASE-II; STEROID-RECEPTOR; CONFORMATIONAL STATES; MOLECULAR CHAPERONES; CLIENT PROTEINS; ATP HYDROLYSIS; IN-VIVO; YEAST; CYCLE AB Heat shock protein 90 (Hsp90) is an essential molecular chaperone whose activity is regulated not only by cochaperones but also by distinct posttranslational modifications. We report here that casein kinase 2 phosphorylates a conserved threonine residue (T22) in alpha helix-1 of the yeast Hsp90 N-domain both in vitro and in vivo. This a helix participates in a hydrophobic interaction with the catalytic loop in Hsp90's middle domain, helping to stabilize the chaperone's ATPase-competent state. Phosphomimetic mutation of this residue alters Hsp90 ATPase activity and chaperone function and impacts interaction with the cochaperones Aha1 and Cdc37. Overexpression of Aha1 stimulates the ATPase activity, restores cochaperone interactions, and compensates for the functional defects of these Hsp90 mutants. C1 [Mollapour, Mehdi; Tsutsumi, Shinji; Xu, Wanping; Beebe, Kristin; Konstantinova, Anna; Vourganti, Srinivas; Neckers, Len] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Trepel, Jane B.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Truman, Andrew W.; Piper, Peter W.] Univ Sheffield, Dept Mol Biol & Biotechnol, Sheffield S10 2TN, S Yorkshire, England. [Vaughan, Cara K.] Birkbeck Coll, Sch Crystallog, Inst Struct & Mol Biol, London WC1E 7HZ, England. [Panaretou, Barry] Kings Coll London, Div Pharmaceut Sci, London SE1 9NH, England. [Prodromou, Chrisostomos; Pearl, Laurence H.] Univ Sussex, Genome Damage & Stabil Ctr, Brighton BN1 9QR, E Sussex, England. RP Neckers, L (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM len@helix.nih.gov OI Pearl, Laurence/0000-0002-6910-1809; Prodromou, Chrisostomos/0000-0003-4320-1147 FU National Cancer Institute FX We thank Drs. C. V. C. Glover for CK2 yeast strains, J. L. Brodsky for the yeast and mammalian CFTR plasmids, M. Yoshida for hAha1 plasmid, M. Siderius for p50-Cdc37-GFP plasmid, J. Johnson for Ste11 Delta N plasmid, and D. C. Masison for anti-Sti1 antibody. This work was supported by the Intramural Research Program of the National Cancer Institute (L.N.). NR 34 TC 66 Z9 68 U1 0 U2 10 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD MAR 18 PY 2011 VL 41 IS 6 BP 672 EP 681 DI 10.1016/j.molcel.2011.02.011 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 740XK UT WOS:000288827500008 PM 21419342 ER PT J AU Sawitzke, JA Costantino, N Li, XT Thomason, LC Bubunenko, M Court, C Court, DL AF Sawitzke, James A. Costantino, Nina Li, Xin-tian Thomason, Lynn C. Bubunenko, Mikhail Court, Carolyn Court, Donald L. TI Probing Cellular Processes with Oligo-Mediated Recombination and Using the Knowledge Gained to Optimize Recombineering SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE mismatch repair; lambda Red; genome engineering; targeted mutagenesis; DNA transformation ID SINGLE-STRANDED OLIGONUCLEOTIDES; BACTERIAL ARTIFICIAL CHROMOSOMES; MISMATCH-REPAIR MUTANTS; ESCHERICHIA-COLI; BACTERIOPHAGE-LAMBDA; DNA; EFFICIENT; MUTAGENESIS; SEQUENCE; IDENTIFICATION AB Recombination with single-strand DNA oligonucleotides (oligos) in Escherichia coli is an efficient and rapid way to modify replicons in vivo. The generation of nucleotide alteration by oligo recombination provides novel assays for studying cellular processes. Single-strand exonucleases inhibit oligo recombination, and recombination is increased by mutating all four known exonucleases. Increasing oligo concentration or adding nonspecific carrier oligo titrates out the exonucleases. In a model for oligo recombination, lambda Beta protein anneals the oligo to complementary single-strand DNA at the replication fork. Mismatches are created, and the methyl-directed mismatch repair (MMR) system acts to eliminate the mismatches inhibiting recombination. Three ways to evade MMR through oligo design include, in addition to the desired change (1) a C.C mismatch 6 bp from that change; (2) four or more adjacent mismatches; or (3) mismatches at four or more consecutive wobble positions. The latter proves useful for making high-frequency changes that alter only the target amino acid sequence and even allows modification of essential genes. Efficient uptake of DNA is important for oligo-mediated recombination. Uptake of oligos or plasmids is dependent on media and is 10,000-fold reduced for cells grown in minimal versus rich medium. Genomewide engineering technologies utilizing recombineering will benefit from both optimized recombination frequencies and a greater understanding of how biological processes such as DNA replication and cell division impact recombinants formed at multiple chromosomal loci. Recombination events at multiple loci in individual cells are described here. Published by Elsevier Ltd. C1 [Sawitzke, James A.; Costantino, Nina; Li, Xin-tian; Bubunenko, Mikhail; Court, Donald L.] NCI, Mol Control & Genet Sect, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res, Frederick, MD 21702 USA. [Thomason, Lynn C.; Bubunenko, Mikhail] NCI, Gene Regulat & Chromosome Biol Lab, Basic Sci Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Court, Carolyn] NCI, Transcript Control Sect, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Court, DL (reprint author), NCI, Mol Control & Genet Sect, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res, Frederick, MD 21702 USA. EM court@ncifcrf.gov FU National Institutes of Health, National Cancer Institute, Center for Cancer Research; National Institutes of Allergy and Infectious Disease; National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX We thank Xiaomei Zhou for helpful discussions and Matthew Fivash for statistical assistance. This work was supported, in part, by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research, and in part by a Trans National Institutes of Health/Food and Drug Administration Intramural Biodefense Program Grant of the National Institutes of Allergy and Infectious Disease (to D.L.C.). This project has also been partly funded with federal funds from the National Cancer Institute, National Institutes of Health, under contract no. HHSN261200800001E. NR 47 TC 61 Z9 64 U1 2 U2 23 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD MAR 18 PY 2011 VL 407 IS 1 BP 45 EP 59 DI 10.1016/j.jmb.2011.01.030 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 739NT UT WOS:000288725500005 PM 21256136 ER PT J AU Haithcock, J Billington, N Choi, K Fordham, J Sellers, JR Stafford, WF White, H Forgacs, E AF Haithcock, Jessica Billington, Neil Choi, Kevin Fordham, Jennifer Sellers, James R. Stafford, Walter F. White, Howard Forgacs, Eva TI The Kinetic Mechanism of Mouse Myosin VIIA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIN-BASED MOTOR; USHER-SYNDROME; SEDIMENTATION-VELOCITY; TRYPTOPHAN RESIDUE; DROSOPHILA; DEAFNESS; DOMAIN; MUTATIONS; PROTEIN; COEFFICIENTS AB Myosin VIIa is crucial in hearing and visual processes. We examined the kinetic and association properties of the baculovirus expressed, truncated mouse myosin VIIa construct containing the head, all 5IQ motifs and the putative coiled coil domain (myosin VIIa-5IQ). The construct appears to be monomeric as determined by analytical ultracentrifugation experiments, and only single headed molecules were detected by negative stain electron microscopy. The relatively high basal steady-state rate of 0.18 s(-1) is activated by actin only by similar to 3.5-fold resulting in a V(max) of 0.7 s(-1) and a K(ATPase) of 11.5 mu M. There is no single rate-limiting step of the ATP hydrolysis cycle. The ATP hydrolysis step (M.T reversible arrow M.D.P) is slow (12 s(-1)) and the equilibrium constant (K(H)) of 1 suggests significant reversal of hydrolysis. In the presence of actin ADP dissociates with a rate constant of 1.2 s(-1). Phosphate dissociation is relatively fast (> 12 s(-1)), but the maximal rate could not be experimentally obtained at actin concentrations <= 50 mu M because of the weak binding of the myosin VIIa-ADP-P(i) complex to actin. At higher actin concentrations the rate of attached hydrolysis (0.4 s(-1)) becomes significant and partially rate-limiting. Our findings suggest that the myosin VIIa is a "slow", monomeric molecular motor with a duty ratio of 0.6. C1 [White, Howard; Forgacs, Eva] Eastern Virginia Med Sch, Dept Physiol Sci, Norfolk, VA 23507 USA. [Fordham, Jennifer] Kings Coll London, Randall Div Cell & Mol Biophys, London SE1 1UL, England. [Billington, Neil; Sellers, James R.] NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. [Stafford, Walter F.] Boston Biomed Res Inst, Integrat Prot Biol Program, Watertown, MA 02472 USA. RP Forgacs, E (reprint author), Eastern Virginia Med Sch, Dept Physiol Sci, Norfolk, VA 23507 USA. EM forgace@evms.edu OI Billington, Neil/0000-0003-2306-0228 FU National Institutes of Health [DC009335, NIH/EB00209] FX This work was supported, in whole or in part, by National Institutes of Health Grant DC009335 (to E. F.) and NIH/EB00209 (to H. W.). NR 49 TC 6 Z9 6 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 18 PY 2011 VL 286 IS 11 BP 8819 EP 8828 DI 10.1074/jbc.M110.163592 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 733FE UT WOS:000288247700012 PM 21212272 ER PT J AU Sricholpech, M Perdivara, I Nagaoka, H Yokoyama, M Tomer, KB Yamauchi, M AF Sricholpech, Marnisa Perdivara, Irina Nagaoka, Hideaki Yokoyama, Megumi Tomer, Kenneth B. Yamauchi, Mitsuo TI Lysyl Hydroxylase 3 Glucosylates Galactosylhydroxylysine Residues in Type I Collagen in Osteoblast Culture SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CROSS-LINKING; BONE-COLLAGEN; GALACTOSYL-HYDROXYLYSINE; POSTTRANSLATIONAL MODIFICATIONS; OSTEOGENESIS IMPERFECTA; LYSINE HYDROXYLATION; TRABECULAR BONE; LYSYL-HYDROXYLASE-3 LH3; BIOCHEMICAL MARKER; URINARY-EXCRETION AB Lysyl hydroxylase 3 (LH3), encoded by Plod3, is the multifunctional collagen-modifying enzyme possessing LH, hydroxylysine galactosyltransferase (GT), and galactosylhydroxylysine-glucosyltransferase (GGT) activities. Although an alteration in type I collagen glycosylation has been implicated in several osteogenic disorders, the role of LH3 in bone physiology has never been investigated. To elucidate the function of LH3 in bone type I collagen modifications, we used a short hairpin RNA technology in a mouse osteoblastic cell line, MC3T3-E1; generated single cell-derived clones stably suppressing LH3 (short hairpin (Sh) clones); and characterized the phenotype. Plod3 expression and the LH3 protein levels in the Sh clones were significantly suppressed when compared with the controls, MC3T3-E1, and the clone transfected with an empty vector. In comparison with controls, type I collagen synthesized by Sh clones (Sh collagen) showed a significant decrease in the extent of glucosylgalactosylhydroxylysine with a concomitant increase of galactosylhydroxylysine, whereas the total number of hydroxylysine residues was essentially unchanged. In an in vitro fibrillogenesis assay, Sh collagen showed accelerated fibrillogenesis compared with the controls. In addition, when recombinant LH3-V5/His protein was generated in 293 cells and subjected to GGT/GT activity assay, it showed GGT but not GT activity against denatured type I collagen. The results from this study clearly indicate that the major function of LH3 in osteoblasts is to glucosylate galactosylhydroxylysine residues in type I collagen and that an impairment of this LH3 function significantly affects type I collagen fibrillogenesis. C1 [Sricholpech, Marnisa; Nagaoka, Hideaki; Yokoyama, Megumi; Yamauchi, Mitsuo] Univ N Carolina, NC Oral Hlth Inst, Sch Dent, Chapel Hill, NC 27599 USA. [Perdivara, Irina; Tomer, Kenneth B.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Yamauchi, M (reprint author), Univ N Carolina, NC Oral Hlth Inst, Sch Dent, CB 7454, Chapel Hill, NC 27599 USA. EM mitsuo_yamauchi@dentistry.unc.edu RI Tomer, Kenneth/E-8018-2013; OI Sricholpech, Marnisa/0000-0003-2139-0688 FU National Institutes of Health [R21DE019569, R01 DE10489]; NIEHS [ES050171] FX This work was supported, in whole or in part, by National Institutes of Health Grants R21DE019569 and R01 DE10489 and Intramural Research Program NIEHS Project ES050171. NR 78 TC 22 Z9 22 U1 4 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 MAR 18 PY 2011 VL 286 IS 11 BP 8846 EP 8856 DI 10.1074/jbc.M110.178509 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 733FE UT WOS:000288247700015 PM 21220425 ER PT J AU Joo, HS Cheung, GYC Otto, M AF Joo, Hwang-Soo Cheung, Gordon Y. C. Otto, Michael TI Antimicrobial Activity of Community-associated Methicillin-resistant Staphylococcus aureus Is Caused by Phenol-soluble Modulin Derivatives SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID VIRULENCE DETERMINANTS; LANTIBIOTIC EPIDERMIN; PREPEPTIDE SEQUENCE; GENOME SEQUENCE; EVOLUTION; PEPTIDES; INFECTION; GENES; AGR; IDENTIFICATION AB Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) are causing an ongoing pandemic of mostly skin and soft tissue infections. The success of CA-MRSA as pathogens is due to a combination of antibiotic resistance with high virulence. In addition, it has been speculated that CA-MRSA strains such as the epidemic U. S. clone USA300 have increased capacity to colonize human epithelia, owing to bacteriocin-based bacterial interference. We here analyzed the molecular basis of antimicrobial activity detected in S. aureus strains, including those of the USA300 lineage. In contrast to a previous hypothesis, we found that this activity is not due to expression of a lantibiotic-type bacteriocin, but proteolytically processed derivatives of the phenol-soluble modulin (PSM) peptides PSM alpha 1 and PSM alpha 2. Notably, processed PSM alpha 1 and PSM alpha 2 exhibited considerable activity against Streptococcus pyogenes, indicating a role of PSMs in the interference of S. aureus strains with the competing colonizing pathogen. Furthermore, by offering a competitive advantage during colonization of the human body, the characteristically high production of PSMs in USA300 and other CA-MRSA strains may thus contribute not only to virulence but also the exceptional capacity of those strains to sustainably spread in the population, which so far has remained poorly understood. C1 [Joo, Hwang-Soo; Cheung, Gordon Y. C.; Otto, Michael] NIAID, Lab Human Bacterial Pathogenesis, NIH, Bethesda, MD 20892 USA. RP Otto, M (reprint author), 9000 Rockville Pike,Bldg 331W10, Bethesda, MD 20892 USA. EM motto@niaid.nih.gov RI Cheung, Yiu Chong /K-3565-2012; OI JOO, HWANG-SOO/0000-0003-4668-3225; Otto, Michael/0000-0002-2222-4115 FU NIAID, National Institutes of Health [ZIA AI000904-08] FX This work was supported, in whole or in part, by the Intramural Research Program of the NIAID, National Institutes of Health (Grant ZIA AI000904-08). NR 42 TC 57 Z9 58 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 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 18 PY 2011 VL 286 IS 11 BP 8933 EP 8940 DI 10.1074/jbc.M111.221382 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 733FE UT WOS:000288247700025 PM 21278255 ER PT J AU Lelouvier, B Puertollano, R AF Lelouvier, Benjamin Puertollano, Rosa TI Mucolipin-3 Regulates Luminal Calcium, Acidification, and Membrane Fusion in the Endosomal Pathway SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID VARITINT-WADDLER PHENOTYPE; CONSTITUTIVE ACTIVITY; MUTATION; MOUSE; MICE; ORGANELLES; DEAFNESS; LEADS; CA2+ AB Mucolipin-3 (MCOLN3) is a pH-regulated Ca2+ channel that localizes to the endosomal pathway. Gain-of-function mutation in MCOLN3 causes the varitint-waddler (Va) phenotype in mice, which is characterized by hearing loss, vestibular dysfunction, and coat color dilution. The Va phenotype results from a punctual mutation (A419P) in the pore region of MCOLN3 that locks the channel in an open conformation causing massive entry of Ca2+ inside cells and inducing cell death by apoptosis. Overexpression of wild-type MCOLN3 produces severe alterations of the endosomal pathway, including enlargement and clustering of endosomes, delayed EGF receptor degradation, and impaired autophagosome maturation, thus suggesting that MCOLN3 plays an important role in the regulation of endosomal function. To understand better the physiological role of MCOLN3, we inhibited MCOLN3 function by expression of a channel-dead dominant negative mutant (458DD/KK) or by knockdown of endogenous MCOLN3. Remarkably, we found that impairment of MCOLN3 activity caused a significant accumulation of luminal Ca2+ in endosomes. This accumulation led to severe defects in endosomal acidification as well as to increased endosomal fusion. Our findings reveal a prominent role for MCOLN3 in regulating Ca2+ homeostasis at the endosomal pathway and confirm the importance of luminal Ca2+ for proper acidification and membrane fusion. C1 [Lelouvier, Benjamin; Puertollano, Rosa] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Puertollano, R (reprint author), NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. EM puertolr@mail.nih.gov FU NHLBI, National Institutes of Health FX This work was supported by the Intramural Research Program of the NHLBI, National Institutes of Health. NR 24 TC 29 Z9 29 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 18 PY 2011 VL 286 IS 11 BP 9826 EP 9832 DI 10.1074/jbc.M110.169185 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 733FE UT WOS:000288247700105 PM 21245134 ER PT J AU Malek, R Matta, J Taylor, N Perry, ME Mendrysa, SM AF Malek, Reem Matta, Jennifer Taylor, Natalie Perry, Mary Ellen Mendrysa, Susan M. TI The p53 Inhibitor MDM2 Facilitates Sonic Hedgehog-Mediated Tumorigenesis and Influences Cerebellar Foliation SO PLOS ONE LA English DT Article ID GRANULE NEURON PRECURSORS; CELL CARCINOMA SYNDROME; EMBRYONIC LETHALITY; MDM2-DEFICIENT MICE; TUMOR SUPPRESSION; MUTANT MICE; MOUSE MODEL; N-MYC; MEDULLOBLASTOMA; PATHWAY AB Disruption of cerebellar granular neuronal precursor (GNP) maturation can result in defects in motor coordination and learning, or in medulloblastoma, the most common childhood brain tumor. The Sonic Hedgehog (Shh) pathway is important for GNP proliferation; however, the factors regulating the extent and timing of GNP proliferation, as well as GNP differentiation and migration are poorly understood. The p53 tumor suppressor has been shown to negatively regulate the activity of the Shh effector, Gli1, in neural stem cells; however, the contribution of p53 to the regulation of Shh signaling in GNPs during cerebellar development has not been determined. Here, we exploited a hypomorphic allele of Mdm2 (Mdm2(puro)), which encodes a critical negative regulator of p53, to alter the level of wild-type MDM2 and p53 in vivo. We report that mice with reduced levels of MDM2 and increased levels of p53 have small cerebella with shortened folia, reminiscent of deficient Shh signaling. Indeed, Shh signaling in Mdm2-deficient GNPs is attenuated, concomitant with decreased expression of the Shh transducers, Gli1 and Gli2. We also find that Shh stimulation of GNPs promotes MDM2 accumulation and enhances phosphorylation at serine 166, a modification known to increase MDM2-p53 binding. Significantly, loss of MDM2 in Ptch1(+/-) mice, a model for Shh-mediated human medulloblastoma, impedes cerebellar tumorigenesis. Together, these results place MDM2 at a major nexus between the p53 and Shh signaling pathways in GNPs, with key roles in cerebellar development, GNP survival, cerebellar foliation, and MB tumorigenesis. C1 [Malek, Reem; Taylor, Natalie; Mendrysa, Susan M.] Purdue Univ, Sch Vet Med, Dept Basic Med Sci, W Lafayette, IN 47907 USA. [Matta, Jennifer] NCI, Lab Anim Sci Program, NIH, Frederick, MD 21701 USA. [Perry, Mary Ellen] NCI, Lab Prot Dynam & Signaling, NIH, Frederick, MD 21701 USA. RP Malek, R (reprint author), Purdue Univ, Sch Vet Med, Dept Basic Med Sci, W Lafayette, IN 47907 USA. EM mendrysa@purdue.edu FU NIH, National Cancer Institute, Center for Cancer Research; Concern Foundation; Alex's Lemonade Stand Foundation for Childhood Cancer FX This work was supported by the Intramural Program of the NIH, National Cancer Institute, Center for Cancer Research (M. E. P.) and by grants to S. M. M. from the Concern Foundation (www.concernfoundation.org) and Alex's Lemonade Stand Foundation for Childhood Cancer (www.alexslemonade.org). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 68 TC 20 Z9 23 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 18 PY 2011 VL 6 IS 3 AR e17884 DI 10.1371/journal.pone.0017884 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 737CD UT WOS:000288545100042 PM 21437245 ER PT J AU Alayash, AI AF Alayash, Abdu I. TI Haptoglobin: Old protein with new functions SO CLINICA CHIMICA ACTA LA English DT Review DE Hemoglobin; Haptoglobin; Redox reactions ID RED-BLOOD-CELLS; HUMAN-HEMOGLOBIN; NITRIC-OXIDE; SCAVENGER RECEPTOR; NITROGEN-OXIDES; OXIDATION; PATHWAY; BINDING; THERAPEUTICS; LOCALIZATION AB When released from red blood cells (RBCs), hemoglobin (Hb) is extremely toxic due in large part to the redox activity of its heme center. Mature however, has provided a multitude of protective mechanisms that can detoxify free Hb effectively under physiological conditions. Chief amongst them is haptoglobin (Hp) which chaperones Hb subunits to the macrophages for safe degradation. Recent research on the interactions between Hb and Hp under oxidative conditions revealed that Hp specifically shields key amino acids on the Hb molecule, allowing the heme to consume oxidants and short-circuits the emerging and damaging radicals. Moreover, animal studies showed that the infusion of Hb complexed with Hp prevents Hb-induced systemic hypertension and tissue injury. It may prove necessary to explore these protective clearing mechanisms to counter the toxicity associated with free Hb when used as oxygen therapeutics in hemolytic anemias and in RBC storage lesions. Published by Elsevier B.V. C1 [Alayash, Abdu I.] US Food & Drug Adm FDA, Lab Biochem & Vasc Biol, Div Hematol, CBER, Bethesda, MD USA. RP Alayash, AI (reprint author), FDA, CBER, NIH Bldg 29,Rm 112,8800 Rockville Pike, Bethesda, MD 20892 USA. EM abdu.alayash@fda.hhs.gov NR 42 TC 35 Z9 38 U1 1 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD MAR 18 PY 2011 VL 412 IS 7-8 BP 493 EP 498 DI 10.1016/j.cca.2010.12.011 PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 727YZ UT WOS:000287840600002 PM 21159311 ER PT J AU Smith, DJ Yap, GPA Kelley, JA Schneider, JP AF Smith, Daniel J. Yap, Glenn P. A. Kelley, James A. Schneider, Joel P. TI Enhanced Stereoselectivity of a Cu(II) Complex Chiral Auxiliary in the Synthesis of Fmoc-L-gamma-carboxyglutamic Acid SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID MICHAEL ADDITION-REACTIONS; ALPHA-AMINO-ACIDS; SUBSTITUTED GLUTAMIC ACIDS; EFFICIENT ASYMMETRIC-SYNTHESIS; VIRTUALLY COMPLETE CONTROL; STEM-CELL DIFFERENTIATION; NI-II COMPLEXES; NUCLEOPHILIC GLYCINE; FACE DIASTEREOSELECTIVITY; PYROGLUTAMIC ACIDS AB L-gamma-Carboxyglutamic acid (Gla) is an uncommon amino acid that binds avidly to mineral surfaces and metal ions. Herein, we report the synthesis of N-alpha-Fmoc-L-gamma-carboxyglutamic acid gamma,gamma'-tert-butyl ester (Fmoc-Gla(O(t)Bu)(2)-OH), a suitably protected analogue for Fmoc-based solid-phase peptide synthesis. The residue was synthesized using a novel chiral Cu(II) complex, whose structure-based design was inspired by the blue copper protein rusticyanin. The five-coordinate complex is formed by Shiff base formation between glycine and the novel ligand (S)-2-(N-(2-methylthio)benzylproly)aminobenzophenone in the presence of copper. Michael addition of di-tert-butyl methylenemalonate to the alpha-carbon of the glycine portion of the complex occurs in a diastereoselective fashion. The resulting (S,S)-complex diastereomer can be easily purified by chromatography. Metal complex decomposition followed by Fmoc protection affords the enantiomerically pure amino acid. With the use of this novel chiral complex, the asymmetric synthesis of Fmoc-Gla(O(t)Bu)(2)-OH was completed in nine steps from thiosalicylic acid in 14.5% overall yield. C1 [Smith, Daniel J.; Kelley, James A.; Schneider, Joel P.] Natl Canc Inst Frederick, Biol Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA. [Smith, Daniel J.; Yap, Glenn P. A.] Univ Delaware, Dept Chem & Biochem, Newark, DE 19716 USA. RP Schneider, JP (reprint author), Natl Canc Inst Frederick, Biol Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA. EM schneiderjp@mail.nih.gov RI Schneider, Joel/N-2610-2014 FU NIH, National Cancer Institute, Center for Cancer Research FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. We are grateful to Dr. Terrence Burke at NCI-CCR for his assistance with the blue copper protein image. We also thank Ms. Hilary Thomas for her assistance in creating the cover art. NR 51 TC 7 Z9 7 U1 2 U2 26 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 MAR 18 PY 2011 VL 76 IS 6 BP 1513 EP 1520 DI 10.1021/jo101940k PG 8 WC Chemistry, Organic SC Chemistry GA 731XD UT WOS:000288142800001 PM 21291260 ER PT J AU Freyer, DR Devidas, M La, M Carroll, WL Gaynon, PS Hunger, SP Seibel, NL AF Freyer, David R. Devidas, Meenakshi La, Mei Carroll, William L. Gaynon, Paul S. Hunger, Stephen P. Seibel, Nita L. TI Postrelapse survival in childhood acute lymphoblastic leukemia is independent of initial treatment intensity: a report from the Children's Oncology Group SO BLOOD LA English DT Article ID BFM STUDY-GROUP; CANCER-GROUP; DELAYED INTENSIFICATION; PRIMARY THERAPY; 1ST RELAPSE; EXPERIENCE; TRIALS; TRANSPLANTATION; CHEMOTHERAPY; MUTATION AB While intensification of therapy has improved event-free survival (EFS) and survival in newly diagnosed children with acute lymphoblastic leukemia (ALL), postrelapse outcomes remain poor. It might be expected that patients relapsing after inferior initial therapy would have a higher retrieval rate than after superior therapy. In the Children's Oncology Group Study CCG-1961, significantly superior EFS and survival were achieved with an augmented (stronger) versus standard intensity regimen of postinduction intensification (PII) for children with newly diagnosed high-risk ALL and rapid day 7 marrow response (EFS/survival 81.2%/88.7% vs 71.7%/83.4%, respectively). This provided an opportunity to evaluate postrelapse survival (PRS) in 272 relapsed patients who had received randomly allocated initial treatment with augmented or standard intensity PII. As expected, PRS was worse for early versus late relapse, marrow versus extramedullary site, adolescent versus younger age and T versus B lineage. However, no difference in 3-year PRS was detected for having received augmented versus standard intensity PII (36.4% +/- 5.7% vs 39.2% +/- 4.1%; log rank P = .72). Similar findings were noted within subanalyses by timing and site of relapse, age, and immunophenotype. These findings provide insight into mechanisms of relapse in ALL, and are consistent with emergence of a resistant subclone that has acquired spontaneous mutations largely independent of initial therapy. This study is registered at www.clinicaltrials.gov as NCT00002812. (Blood. 2011; 117(11):3010-3015) C1 [Freyer, David R.; Gaynon, Paul S.] Univ So Calif, Childrens Ctr Canc & Blood Dis, Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Freyer, David R.; Gaynon, Paul S.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90027 USA. [Devidas, Meenakshi] Univ Florida, Coll Med, Dept Epidemiol & Hlth Policy Res, Gainesville, FL USA. [Devidas, Meenakshi; La, Mei] Childrens Oncol Grp, Arcadia, CA USA. [Carroll, William L.] NYU, Inst Canc, New York, NY USA. [Hunger, Stephen P.] Childrens Hosp, Dept Pediat, Aurora, CO USA. [Hunger, Stephen P.] Univ Colorado, Ctr Canc, Aurora, CO USA. [Seibel, Nita L.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Freyer, DR (reprint author), Univ So Calif, Childrens Ctr Canc & Blood Dis, Childrens Hosp Los Angeles, 4650 Sunset Blvd,Mailstop 54, Los Angeles, CA 90027 USA. EM dfreyer@chla.usc.edu FU National Institutes of Health [U10 CA98543, CA13539, CA30969] FX This work was supported by the National Institutes of Health (grants U10 CA98543, CA13539, and CA30969). NR 47 TC 25 Z9 26 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 17 PY 2011 VL 117 IS 11 BP 3010 EP 3015 DI 10.1182/blood-2010-07-294678 PG 6 WC Hematology SC Hematology GA 736LN UT WOS:000288496300009 PM 21193696 ER PT J AU Zhu, JQ Chin, K Aerbajinai, W Trainor, C Gao, P Rodgers, GP AF Zhu, Jianqiong Chin, Kyung Aerbajinai, Wulin Trainor, Cecelia Gao, Peter Rodgers, Griffin P. TI Recombinant erythroid Kruppel-like factor fused to GATA1 up-regulates delta- and gamma-globin expression in erythroid cells SO BLOOD LA English DT Article ID TRANSCRIPTION FACTOR GATA-1; GENE-EXPRESSION; FETAL-HEMOGLOBIN; BETA-THALASSEMIA; RISK-FACTORS; ZINC-FINGER; CACCC MOTIF; DNA-BINDING; ACTIVATION; PROMOTER AB The beta-hemoglobinopathies sickle cell disease and beta-thalassemia are among the most common human genetic disorders worldwide. Hemoglobin A2 (HbA2, alpha(2)delta(2)) and fetal hemoglobin (HbF, alpha(2)gamma(2)) both inhibit the polymerization of hemoglobin S, which results in erythrocyte sickling. Expression of erythroid Kruppel-like factor (EKLF) and GATA1 is critical for transitioning hemoglobin from HbF to hemoglobin A (HbA, alpha(2 beta 2)) and HbA2. The lower levels of delta-globin expression compared with beta-globin expression seen in adult-hood are likely due to the absence of an EKLF-binding motif in the delta-globin proximal promoter. In an effort to up-regulate delta-globin to increase HbA2 expression, we created a series of EKLF-GATA1 fusion constructs composed of the transactivation domain of EKLF and the DNA-binding domain of GATA1, and then tested their effects on hemoglobin expression. EKLF-GATA1 fusion proteins activated delta-, gamma-, and beta-globin promoters in K562 cells, and significantly up-regulated delta- and gamma-globin RNA transcript and protein ex-pression in K562 and/or CD34(+) cells. The binding of EKLF-GATA1 fusion proteins at the GATA1 consensus site in the delta-globin promoter was confirmed by chromatin immunoprecipitation assay. Our studies demonstrate that EKLF-GATA1 fusion proteins can enhance delta-globin expression through interaction with the delta-globin promoter, and may represent a new genetic therapeutic approach to beta-hemoglobinopathies. (Blood. 2011; 117(11):3045-3052) C1 [Zhu, Jianqiong; Chin, Kyung; Aerbajinai, Wulin; Gao, Peter; Rodgers, Griffin P.] NHLBI, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. [Trainor, Cecelia] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Rodgers, GP (reprint author), NHLBI, Mol & Clin Hematol Branch, NIH, Bldg 10,Rm 9N119,10 Ctr Dr, Bethesda, MD 20892 USA. EM gr5n@nih.gov FU National Heart, Lung, and Blood Institute, National Institutes of Health FX This work was supported by the Intramural Research Program of the National Heart, Lung, and Blood Institute, National Institutes of Health. NR 42 TC 8 Z9 8 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 17 PY 2011 VL 117 IS 11 BP 3045 EP 3052 DI 10.1182/blood-2010-07-294751 PG 8 WC Hematology SC Hematology GA 736LN UT WOS:000288496300014 PM 21220744 ER PT J AU Cheng, HY Zhang, LN Cogdell, DE Zheng, H Schetter, AJ Nykter, M Harris, CC Chen, KX Hamilton, SR Zhang, W AF Cheng, Hanyin Zhang, Lina Cogdell, David E. Zheng, Hong Schetter, Aaron J. Nykter, Matti Harris, Curtis C. Chen, Kexin Hamilton, Stanley R. Zhang, Wei TI Circulating Plasma MiR-141 Is a Novel Biomarker for Metastatic Colon Cancer and Predicts Poor Prognosis SO PLOS ONE LA English DT Article ID TUMOR-SUPPRESSOR GENE; COLORECTAL-CANCER; EXPRESSION; MICRORNAS; TARGETS; CELLS; ZEB1 AB Background: Colorectal cancer (CRC) remains one of the major cancer types and cancer related death worldwide. Sensitive, non-invasive biomarkers that can facilitate disease detection, staging and prediction of therapeutic outcome are highly desirable to improve survival rate and help to determine optimized treatment for CRC. The small non-coding RNAs, microRNAs (miRNAs), have recently been identified as critical regulators for various diseases including cancer and may represent a novel class of cancer biomarkers. The purpose of this study was to identify and validate circulating microRNAs in human plasma for use as such biomarkers in colon cancer. Methodology/Principal Findings: By using quantitative reverse transcription-polymerase chain reaction, we found that circulating miR-141 was significantly associated with stage IV colon cancer in a cohort of 102 plasma samples. Receiver operating characteristic (ROC) analysis was used to evaluate the sensitivity and specificity of candidate plasma microRNA markers. We observed that combination of miR-141 and carcinoembryonic antigen (CEA), a widely used marker for CRC, further improved the accuracy of detection. These findings were validated in an independent cohort of 156 plasma samples collected at Tianjin, China. Furthermore, our analysis showed that high levels of plasma miR-141 predicted poor survival in both cohorts and that miR-141 was an independent prognostic factor for advanced colon cancer. Conclusions/Significance: We propose that plasma miR-141 may represent a novel biomarker that complements CEA in detecting colon cancer with distant metastasis and that high levels of miR-141 in plasma were associated with poor prognosis. C1 [Cheng, Hanyin; Cogdell, David E.; Hamilton, Stanley R.; Zhang, Wei] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Zhang, Lina; Zheng, Hong; Chen, Kexin] Tianjin Med Univ Canc Inst & Hosp, Dept Epidemiol & Biostat, Tianjin, Peoples R China. [Schetter, Aaron J.; Harris, Curtis C.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Nykter, Matti] Tampere Univ Technol, Dept Signal Proc, FIN-33101 Tampere, Finland. RP Cheng, HY (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. EM chenkexin1963@yahoo.com; shamilto@mdanderson.org; wzhang@mdanderson.org FU National Foundation for Cancer Research; Tianjin Cancer Institute and Hospital; NIH [R90 DK071505-05]; M. D. Anderson University; Center for Clinical and Translational Sciences of the University of Texas Health Science Center at Houston; NIH Cancer Center [CA16672]; TexGen Research FX This work was partially supported by a grant from the National Foundation for Cancer Research (WZ and SRH) and Tianjin Cancer Institute and Hospital (KC). Hanyin Cheng was supported by a Pharmacoinformatic Training Grant fellowship from NIH (NIH Grant No. R90 DK071505-05). Data and sample collection were supported by the M. D. Anderson University Cancer Fund, the Center for Clinical and Translational Sciences of the University of Texas Health Science Center at Houston, and NIH Cancer Center Support Grant CA16672. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; We would like to thank Ms. Elizabeth G. Thompson for her help with the handling of the samples and TexGen Research for its support and permission to use its data and samples. The authors would also like to thank Ms. Kate Newberry from the Department of Scientific Publications for editing this manuscript. NR 24 TC 206 Z9 233 U1 6 U2 39 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 17 PY 2011 VL 6 IS 3 AR e17745 DI 10.1371/journal.pone.0017745 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 736SO UT WOS:000288514600012 PM 21445232 ER PT J AU Gassman, NR Clodfelter, JE McCauley, AK Bonin, K Salsbury, FR Scarpinato, KD AF Gassman, Natalie R. Clodfelter, Jill E. McCauley, Anita K. Bonin, Keith Salsbury, Freddie R., Jr. Scarpinato, Karin D. TI Cooperative Nuclear Localization Sequences Lend a Novel Role to the N-Terminal Region of MSH6 SO PLOS ONE LA English DT Article ID DNA MISMATCH REPAIR; PROTEINS MSH2; IMPORTIN-ALPHA; CANCER; SIGNALS; MUTATIONS; IDENTIFICATION; TRANSLOCATION; BINDING; CELLS AB Human mismatch repair proteins MSH2-MSH6 play an essential role in maintaining genetic stability and preventing disease. While protein functions have been extensively studied, the substantial amino-terminal region (NTR*) of MSH6 that is unique to eukaryotic proteins, has mostly evaded functional characterization. We demonstrate that a cluster of three nuclear localization signals (NLS) in the NTR direct nuclear import. Individual NLSs are capable of partially directing cytoplasmic protein into the nucleus; however only cooperative effects between all three NLSs efficiently transport MSH6 into the nucleus. In striking contrast to yeast and previous assumptions on required heterodimerization, human MSH6 does not determine localization of its heterodimeric partner, MSH2. A cancer-derived mutation localized between two of the three NLS significantly decreases nuclear localization of MSH6, suggesting altered protein localization can contribute to carcinogenesis. These results clarify the pending speculations on the functional role of the NTR in human MSH6 and identify a novel, cooperative nuclear localization signal. C1 [Gassman, Natalie R.; Clodfelter, Jill E.; Scarpinato, Karin D.] Wake Forest Univ, Bowman Gray Sch Med, Dept Canc Biol, Winston Salem, NC USA. [McCauley, Anita K.] Wake Forest Univ, Dept Biol, Winston Salem, NC 27109 USA. [Bonin, Keith; Salsbury, Freddie R., Jr.] Wake Forest Univ, Dept Phys, Winston Salem, NC 27109 USA. [Salsbury, Freddie R., Jr.; Scarpinato, Karin D.] Wake Forest Univ, Bowman Gray Sch Med, Ctr Comprehens Canc, Winston Salem, NC USA. RP Gassman, NR (reprint author), NIEHS, Durham, NC USA. EM kscarpin@wfubmc.edu RI Bonin, Keith/A-3207-2014; OI Bonin, Keith/0000-0002-7594-823X; Gassman, Natalie/0000-0002-8488-2332 FU National Cancer Institute (NCI) [CA101829, 5R01CA12937]; Comprehensive Cancer Center; National Science Foundation [0722926] FX This work was in part supported by a grant from the National Cancer Institute (NCI) (CA101829) and support from the Comprehensive Cancer Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NCI or the National Institutes of Health. FRS is partially supported by NCI grant 5R01CA12937. The Zeiss LSM 710 confocal microscope was funded by National Science Foundation MRI award number 0722926. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding received for this study. NR 48 TC 9 Z9 9 U1 2 U2 15 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 17 PY 2011 VL 6 IS 3 AR e17907 DI 10.1371/journal.pone.0017907 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 736SO UT WOS:000288514600015 PM 21437237 ER PT J AU Xu, Q Yao, JZ Wlodawer, A Guo, H AF Xu, Qin Yao, Jianzhuang Wlodawer, Alexander Guo, Hong TI Clarification of the Mechanism of Acylation Reaction and Origin of Substrate Specificity of the Serine-Carboxyl Peptidase Sedolisin through QM/MM Free Energy Simulations SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID NEURONAL CEROID-LIPOFUSCINOSIS; ANGSTROM CRYSTAL-STRUCTURE; SCC-DFTB METHOD; MOLECULAR-DYNAMICS; KUMAMOLISIN-AS; TETRAHEDRAL ADDUCT; CATALYTIC RESIDUES; ACTIVE-SITE; PROTEINASE; PURIFICATION AB Quantum mechanical/molecular mechanical (QM/MM) free energy simulations are applied for understanding the mechanism of the acylation reaction catalyzed by sedolisin, a representative serine-carboxyl peptidase, leading to the acyl-enzyme (AE) and first product from the enzyme-catalyzed reaction. One of the interesting questions to be addressed in this work is the origin of the substrate specificity of sedolisin that shows a relatively high activity on the substrates with Glu at P-1 site. It is shown that the bond making and breaking events of the acylation reaction involving a peptide substrate (LLE*FL) seem to be accompanied by local conformational changes, proton transfers as well as the formation of alternative hydrogen bonds. The results of the simulations indicate that the conformational change of Glu at PI site and its formation of a low barrier hydrogen bond with Asp-170 (along with the transient proton transfer) during the acylation reaction might play a role in the relatively high specificity for the substrate with Glu at PI site. The role of some key residues in the catalysis is confirmed through free energy simulations. Glu-80 is found to act as a general base to accept a proton from Ser-287 during the nucleophilic attack and then as a general acid to protonate the leaving group (N-H of P-1-Phe) during the cleavage of the scissile peptide bond. Another acidic residue, Asp-170, acts as a general acid catalyst to protonate the carbonyl of P-1-Glu during the formation of the tetrahedral intermediate and as a general base for the formation of the acyl-enzyme. The energetic results from the free energy simulations support the importance of proton transfer from Asp-170 to the carbonyl of P-1-Glu in the stabilization of the tetrahedral intermediate and the formation of a low-barrier hydrogen bond between the carboxyl group of P-1-Glu and Asp-170 in the lowering of the free energy barrier for the cleavage of the peptide bond. Detailed analyses of the proton transfers during acylation are also given. C1 [Xu, Qin; Yao, Jianzhuang; Guo, Hong] Univ Tennessee, Dept Biochem & Cellular & Mol Biol, Knoxville, TN 37996 USA. [Wlodawer, Alexander] NCI, Prot Struct Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA. RP Guo, H (reprint author), Univ Tennessee, Dept Biochem & Cellular & Mol Biol, Knoxville, TN 37996 USA. EM hguo1@utk.edu RI Guo, Hong/E-6357-2010; Xu, Qin/O-7310-2015 OI Xu, Qin/0000-0002-8346-9431 FU National Science Foundation [0817940]; NIH, National Cancer Institute, Center for Cancer Research FX We thank Professors Martin Karplus for a gift of the CHARMM program and Toru Nakayama for useful discussions. This work was supported in part by National Science Foundation (Grant 0817940 to H.G.) and in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 42 TC 6 Z9 6 U1 0 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD MAR 17 PY 2011 VL 115 IS 10 BP 2470 EP 2476 DI 10.1021/jp1122294 PG 7 WC Chemistry, Physical SC Chemistry GA 731NF UT WOS:000288113300039 PM 21332137 ER PT J AU Steidl, C Shah, SP Woolcock, BW Rui, LX Kawahara, M Farinha, P Johnson, NA Zhao, YJ Telenius, A Ben Neriah, S McPherson, A Meissner, B Okoye, UC Diepstra, A van den Berg, A Sun, M Leung, G Jones, SJ Connors, JM Huntsman, DG Savage, KJ Rimsza, LM Horsman, DE Staudt, LM Steidl, U Marra, MA Gascoyne, RD AF Steidl, Christian Shah, Sohrab P. Woolcock, Bruce W. Rui, Lixin Kawahara, Masahiro Farinha, Pedro Johnson, Nathalie A. Zhao, Yongjun Telenius, Adele Ben Neriah, Susana McPherson, Andrew Meissner, Barbara Okoye, Ujunwa C. Diepstra, Arjan van den Berg, Anke Sun, Mark Leung, Gillian Jones, Steven J. Connors, Joseph M. Huntsman, David G. Savage, Kerry J. Rimsza, Lisa M. Horsman, Douglas E. Staudt, Louis M. Steidl, Ulrich Marra, Marco A. Gascoyne, Randy D. TI MHC class II transactivator CIITA is a recurrent gene fusion partner in lymphoid cancers SO NATURE LA English DT Article ID B-CELL LYMPHOMA; POOR PATIENT SURVIVAL; REED-STERNBERG CELLS; HODGKIN LYMPHOMA; PROTEIN EXPRESSION; LINE; JAK2; TRANSLOCATION; ABERRATIONS; RESOLUTION AB Chromosomal translocations are critically involved in the molecular pathogenesis of B-cell lymphomas, and highly recurrent and specific rearrangements have defined distinct molecular subtypes linked to unique clinicopathological features(1,2). In contrast, several well-characterized lymphoma entities still lack disease-defining translocation events. To identify novel fusion transcripts resulting from translocations, we investigated two Hodgkin lymphoma cell lines by whole-transcriptome paired-end sequencing (RNA-seq). Here we show a highly expressed gene fusion involving the major histocompatibility complex (MHC) class II transactivator CIITA (MHC2TA) in KM-H2 cells. In a subsequent evaluation of 263 B-cell lymphomas, we also demonstrate that genomic CIITA breaks are highly recurrent in primary mediastinal B-cell lymphoma (38%) and classical Hodgkin lymphoma (cHL) (15%). Furthermore, we find that CIITA is a promiscuous partner of various in-frame gene fusions, and we report that CIITA gene alterations impact survival in primary mediastinal B-cell lymphoma (PMBCL). As functional consequences of CIITA gene fusions, we identify downregulation of surface HLA class II expression and overexpression of ligands of the receptor molecule programmed cell death 1 (CD274/PDL1 and CD273/PDL2). These receptor-ligand interactions have been shown to impact anti-tumour immune responses in several cancers(3), whereas decreased MHC class II expression has been linked to reduced tumour cell immunogenicity(4). Thus, our findings suggest that recurrent rearrangements of CIITA may represent a novel genetic mechanism underlying tumour-microenvironment interactions across a spectrum of lymphoid cancers. C1 [Steidl, Christian; Shah, Sohrab P.; Woolcock, Bruce W.; Farinha, Pedro; Johnson, Nathalie A.; Telenius, Adele; Ben Neriah, Susana; McPherson, Andrew; Meissner, Barbara; Sun, Mark; Leung, Gillian; Huntsman, David G.; Horsman, Douglas E.; Gascoyne, Randy D.] Ctr Lymphoid Cancers, Dept Pathol & Lab Med, Vancouver, BC V5Z 4E6, Canada. [Steidl, Christian; Shah, Sohrab P.; Woolcock, Bruce W.; Farinha, Pedro; Johnson, Nathalie A.; Telenius, Adele; Ben Neriah, Susana; McPherson, Andrew; Meissner, Barbara; Sun, Mark; Leung, Gillian; Huntsman, David G.; Horsman, Douglas E.; Gascoyne, Randy D.] Ctr Translat & Appl Genom, Vancouver, BC V5Z 4E6, Canada. [Rui, Lixin; Staudt, Louis M.] NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Kawahara, Masahiro; Okoye, Ujunwa C.; Steidl, Ulrich] Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA. [Kawahara, Masahiro; Okoye, Ujunwa C.; Steidl, Ulrich] Albert Einstein Coll Med, Albert Einstein Canc Ctr, Bronx, NY 10461 USA. [Zhao, Yongjun; Jones, Steven J.; Marra, Marco A.] BC Canc Agcy, Genome Sci Ctr, Vancouver, BC V5Z 4S6, Canada. [Diepstra, Arjan; van den Berg, Anke] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol & Med Biol, NL-9700 AB Groningen, Netherlands. [Connors, Joseph M.; Savage, Kerry J.] BC Canc Agcy Ctr Lymphoid Canc, Div Med Oncol, Vancouver, BC V5Z 4E6, Canada. [Rimsza, Lisa M.] Univ Arizona, Dept Pathol, Tucson, AZ 85724 USA. [Marra, Marco A.] Univ British Columbia, Dept Med Genet, Vancouver, BC V6T 1Z3, Canada. RP Gascoyne, RD (reprint author), Ctr Lymphoid Cancers, Dept Pathol & Lab Med, Vancouver, BC V5Z 4E6, Canada. EM rgascoyn@bccancer.bc.ca RI van den Berg, Anke/H-1718-2011; Tang, Macy/B-9798-2014; Jones, Steven/C-3621-2009; Marra, Marco/B-5987-2008; OI Farinha, Pedro/0000-0001-9364-9391 FU Cancer Research Society; Michael Smith Foundation for Health Research; Lymphoma Research Foundation; Canadian Breast Cancer Foundation; Canadian Institutes of Health Research [178536]; Terry Fox Foundation [019001]; Genome Canada/Genome BC; National Institutes of Health/National Cancer Institute [R00CA131503]; Leukemia Research Foundation; National Health and Medical Research Council of Australia FX This work is supported by a postdoctoral fellowship of the Cancer Research Society (Steven E. Drabin Fellowship) to C. S., the Michael Smith Foundation for Health Research to C. S. and S. P. S., the Lymphoma Research Foundation to C. S. and the Canadian Breast Cancer Foundation to S. P. S. Operational funds were available through the Canadian Institutes of Health Research, grant number 178536 to R. D. G. R. D. G., J.M.C., M. A. M. and D. E. H. are also supported by the Terry Fox Foundation ( number 019001). This work was in part supported by an infrastructure grant of Genome Canada/Genome BC. U. S. is the recipient of a Howard Temin Award of the National Institutes of Health/National Cancer Institute (R00CA131503), a new investigator award of the Leukemia Research Foundation, and is the Diane and Arthur B. Belfer Faculty Scholar in Cancer Research of the Albert Einstein College of Medicine. We thank G. Simkin, C. Polumbo and T. Vogler for technical support. L. R. is the recipient of a CJ Martin Fellowship from the National Health and Medical Research Council of Australia. NR 41 TC 211 Z9 217 U1 3 U2 34 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD MAR 17 PY 2011 VL 471 IS 7338 BP 377 EP + DI 10.1038/nature09754 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 735UE UT WOS:000288444000045 PM 21368758 ER PT J AU Yanovski, SZ Yanovski, JA AF Yanovski, Susan Z. Yanovski, Jack A. TI Obesity Prevalence in the United States - Up, Down, or Sideways? SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ADULTS C1 [Yanovski, Susan Z.] NIDDKD, Off Obes Res, Bethesda, MD 20892 USA. [Yanovski, Jack A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Program Dev Endocrinol & Genet, Bethesda, MD USA. RP Yanovski, SZ (reprint author), NIDDKD, Off Obes Res, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 HD999999, ZIA HD000641-16] NR 4 TC 73 Z9 80 U1 0 U2 8 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 17 PY 2011 VL 364 IS 11 BP 987 EP 989 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 735SX UT WOS:000288439000002 PM 21410367 ER PT J AU Adzick, NS Thom, EA Spong, CY Brock, JW Burrows, PK Johnson, MP Howell, LJ Farrell, JA Dabrowiak, ME Sutton, LN Gupta, N Tulipan, NB D'Alton, ME Farmer, DL AF Adzick, N. Scott Thom, Elizabeth A. Spong, Catherine Y. Brock, John W., III Burrows, Pamela K. Johnson, Mark P. Howell, Lori J. Farrell, Jody A. Dabrowiak, Mary E. Sutton, Leslie N. Gupta, Nalin Tulipan, Noel B. D'Alton, Mary E. Farmer, Diana L. CA MOMS Investigators TI A Randomized Trial of Prenatal versus Postnatal Repair of Myelomeningocele SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MATERNAL-FETAL SURGERY; IN-UTERO; HINDBRAIN HERNIATION; SPINA-BIFIDA; CLINICAL-TRIALS; SHEEP; MENINGOMYELOCELE; OUTCOMES; MODEL AB BACKGROUND Prenatal repair of myelomeningocele, the most common form of spina bifida, may result in better neurologic function than repair deferred until after delivery. We compared outcomes of in utero repair with standard postnatal repair. METHODS We randomly assigned eligible women to undergo either prenatal surgery before 26 weeks of gestation or standard postnatal repair. One primary outcome was a composite of fetal or neonatal death or the need for placement of a cerebrospinal fluid shunt by the age of 12 months. Another primary outcome at 30 months was a composite of mental development and motor function. RESULTS The trial was stopped for efficacy of prenatal surgery after the recruitment of 183 of a planned 200 patients. This report is based on results in 158 patients whose children were evaluated at 12 months. The first primary outcome occurred in 68% of the infants in the prenatal-surgery group and in 98% of those in the postnatal-surgery group (relative risk, 0.70; 97.7% confidence interval [CI], 0.58 to 0.84; P<0.001). Actual rates of shunt placement were 40% in the prenatal-surgery group and 82% in the postnatal-surgery group (relative risk, 0.48; 97.7% CI, 0.36 to 0.64; P<0.001). Prenatal surgery also resulted in improvement in the composite score for mental development and motor function at 30 months (P = 0.007) and in improvement in several secondary outcomes, including hindbrain herniation by 12 months and ambulation by 30 months. However, prenatal surgery was associated with an increased risk of preterm delivery and uterine dehiscence at delivery. CONCLUSIONS Prenatal surgery for myelomeningocele reduced the need for shunting and improved motor outcomes at 30 months but was associated with maternal and fetal risks. C1 [Adzick, N. Scott] Childrens Hosp Philadelphia, Ctr Fetal Diag & Treatment, Philadelphia, PA 19104 USA. [Adzick, N. Scott; Johnson, Mark P.; Howell, Lori J.; Sutton, Leslie N.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Thom, Elizabeth A.; Burrows, Pamela K.] George Washington Univ, Ctr Biostat, Washington, DC USA. [Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Brock, John W., III; Dabrowiak, Mary E.; Tulipan, Noel B.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Farrell, Jody A.; Gupta, Nalin; Farmer, Diana L.] Univ Calif San Francisco, Benioff Childrens Hosp, San Francisco, CA 94143 USA. [Farrell, Jody A.; Gupta, Nalin; Farmer, Diana L.] Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. [D'Alton, Mary E.] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. RP Adzick, NS (reprint author), Childrens Hosp Philadelphia, Ctr Fetal Diag & Treatment, 34th St & Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM adzick@email.chop.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [U10 HD041666, U01HD041665, U10 HD041667, U10 HD041669]; National Institutes of Health [UL1-RR-024134, UL1-RR-024131, UL1-RR-024975] FX Supported by grants (U10 HD041666, U01HD041665, U10 HD041667, and U10 HD041669) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and by grants (UL1-RR-024134, UL1-RR-024131, and UL1-RR-024975) from the Clinical and Translational Science Awards, National Institutes of Health. NR 28 TC 354 Z9 370 U1 5 U2 44 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 17 PY 2011 VL 364 IS 11 BP 993 EP 1004 DI 10.1056/NEJMoa1014379 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 735SX UT WOS:000288439000005 PM 21306277 ER PT J AU Busse, WW Morgan, WJ Gergen, PJ Mitchell, HE Gern, JE Liu, AH Gruchalla, RS Kattan, M Teach, SJ Pongracic, JA Chmiel, JF Steinbach, SF Calatroni, A Togias, A Thompson, KM Szefler, SJ Sorkness, CA AF Busse, William W. Morgan, Wayne J. Gergen, Peter J. Mitchell, Herman E. Gern, James E. Liu, Andrew H. Gruchalla, Rebecca S. Kattan, Meyer Teach, Stephen J. Pongracic, Jacqueline A. Chmiel, James F. Steinbach, Suzanne F. Calatroni, Agustin Togias, Alkis Thompson, Katherine M. Szefler, Stanley J. Sorkness, Christine A. TI Randomized Trial of Omalizumab (Anti-IgE) for Asthma in Inner-City Children SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID SEVERE ALLERGIC-ASTHMA; MONOCLONAL-ANTIBODY; COST-EFFECTIVENESS; CHILDHOOD ASTHMA; EXACERBATIONS; VIRUSES; ADULTS; CELLS; ADOLESCENTS; RHINOVIRUS AB BACKGROUND Research has underscored the effects of exposure and sensitization to allergens on the severity of asthma in inner-city children. It has also revealed the limitations of environmental remediation and guidelines-based therapy in achieving greater disease control. METHODS We enrolled inner-city children, adolescents, and young adults with persistent asthma in a randomized, double-blind, placebo-controlled, parallel-group trial at multiple centers to assess the effectiveness of omalizumab, as compared with placebo, when added to guidelines-based therapy. The trial was conducted for 60 weeks, and the primary outcome was symptoms of asthma. RESULTS Among 419 participants who underwent randomization (at which point 73% had moderate or severe disease), omalizumab as compared with placebo significantly reduced the number of days with asthma symptoms, from 1.96 to 1.48 days per 2-week interval, a 24.5% decrease (P<0.001). Similarly, omalizumab significantly reduced the proportion of participants who had one or more exacerbations from 48.8 to 30.3% (P<0.001). Improvements occurred with omalizumab despite reductions in the use of inhaled glucocorticoids and long-acting beta-agonists. CONCLUSIONS When added to a regimen of guidelines-based therapy for inner-city children, adolescents, and young adults, omalizumab further improved asthma control, nearly eliminated seasonal peaks in exacerbations, and reduced the need for other medications to control asthma. C1 [Busse, William W.; Gern, James E.; Sorkness, Christine A.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53719 USA. [Morgan, Wayne J.] Univ Arizona, Coll Med, Tucson, AZ USA. [Gergen, Peter J.; Togias, Alkis; Thompson, Katherine M.] NIAID, Bethesda, MD 20892 USA. [Mitchell, Herman E.; Calatroni, Agustin] Rho Fed Syst Div, Chapel Hill, NC USA. [Liu, Andrew H.; Szefler, Stanley J.] Natl Jewish Hlth, Denver, CO USA. [Liu, Andrew H.; Szefler, Stanley J.] Univ Colorado Hlth Sci, Denver, CO USA. [Gruchalla, Rebecca S.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Kattan, Meyer] Columbia Univ, Coll Phys & Surg, New York, NY USA. [Teach, Stephen J.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Pongracic, Jacqueline A.] Childrens Mem Hosp, Chicago, IL 60614 USA. [Chmiel, James F.] Rainbow Babies & Childrens Hosp, Cleveland, OH USA. [Steinbach, Suzanne F.] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Busse, WW (reprint author), Univ Wisconsin, Sch Med & Publ Hlth K4 910 CSC, MC 9988,600 Highland Ave, Madison, WI 53719 USA. EM wwb@medicine.wisc.edu FU National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH) [NO1-AI-25496, NO1-AI-25482]; National Center for Research Resources, NIH [M01RR00533, 1UL1RR025771, M01RR00071, 1UL1RR024156, 5M01RR020359-040]; Novartis Pharmaceuticals; Dey Pharma; Boehringer Ingelheim; Teva; Amgen; Pfizer; Genentech; AstraZeneca; GlaxoSmithKline; MedImmune; Novartis; Ception; Phadia; Vertex; Biota; Centocor; Synairgen; Merck; 3V BioSciences; EraGen Biosciences; Ross Abbott; Sandoz; ScheringPlough FX Supported by contracts with the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH) (NO1-AI-25496 and NO1-AI-25482); grants from the National Center for Research Resources, NIH (M01RR00533, 1UL1RR025771, M01RR00071, 1UL1RR024156, and 5M01RR020359-040); Novartis Pharmaceuticals, under a clinical trial agreement with the University of Wisconsin-Madison; Dey Pharma (which provided EpiPens), and SC Johnson (which provided household pest control).; Dr. Busse reports receiving board membership fees from Centocor and Merck, consulting fees from Boehringer Ingelheim, Teva, Amgen, Pfizer, and Genentech; consulting fees and grant support from AstraZeneca, GlaxoSmithKline, MedImmune, and Novartis; and grant support from Ception. Dr. Morgan reports receiving consulting fees from Novartis, lecture fees from Phadia and Vertex, royalties from Elsevier, consulting fees from Genentech, and payment to his institution for development of educational presentations from Genentech. Dr Gern reports receiving consulting fees from GlaxoSmithKline, Biota, Centocor, Synairgen, and Boehringer Ingelheim; grant support from Merck and AstraZeneca; stock options and consulting fees from 3V BioSciences; and stock payments from EraGen Biosciences. Dr. Liu reports receiving consulting fees from AstraZeneca and Novartis and lecture fees from Glaxo-SmithKline, Merck and Phadia. Dr. Teach reports receiving consulting fees from AstraZeneca. Dr. Steinbach reports providing expert testimony for Harvard Medical Institutions. Dr. Szefler reports receiving consulting fees from Schering, Boehringer Ingelheim, and Novartis, consulting fees and grant support from Merck and Genentech, and grant support from GlaxoSmithKline and Ross Abbott. Dr. Sorkness reports receiving consulting fees from GlaxoSmithKline and AstraZeneca, grant support from Pharmaxis and Sandoz, and consulting fees and grant support from ScheringPlough. No other potential conflict of interest relevant to this article was reported. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. NR 42 TC 271 Z9 281 U1 0 U2 22 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 17 PY 2011 VL 364 IS 11 BP 1005 EP 1015 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 735SX UT WOS:000288439000006 PM 21410369 ER PT J AU Masuda, K Abdelmohsen, K Kim, MM Srikantan, S Lee, EK Tominaga, K Selimyan, R Martindale, JL Yang, XL Lehrmann, E Zhang, YQ Becker, KG Wang, JY Kim, HH Gorospe, M AF Masuda, Kiyoshi Abdelmohsen, Kotb Kim, Mihee M. Srikantan, Subramanya Lee, Eun Kyung Tominaga, Kumiko Selimyan, Roza Martindale, Jennifer L. Yang, Xiaoling Lehrmann, Elin Zhang, Yongqing Becker, Kevin G. Wang, Jian-Ying Kim, Hyeon Ho Gorospe, Myriam TI Global dissociation of HuR-mRNA complexes promotes cell survival after ionizing radiation SO EMBO JOURNAL LA English DT Article DE Chk2; HuR phosphorylation; radiotherapy; ribonucleoprotein complex; RNA-binding protein ID DNA-DAMAGE RESPONSE; BINDING PROTEIN HUR; AUTOSOMAL SEX REVERSAL; TUMOR-SUPPRESSOR; NUCLEAR IMPORT; INDUCED PHOSPHORYLATION; TRANSLATIONAL CONTROL; CAMPOMELIC DYSPLASIA; CANCER-CELLS; CHK2 AB Ionizing radiation (IR) triggers adaptive changes in gene expression. Here, we show that survival after IR strongly depends on the checkpoint kinase Chk2 acting upon its substrate HuR, an RNA-binding protein that stabilizes and/or modulates the translation of target mRNAs. Microarray analysis showed that in human HCT116 colorectal carcinoma cells (WT), IR-activated Chk2 triggered the dissociation of virtually all of HuR-bound mRNAs, since IR did not dissociate HuR target mRNAs in Chk2-null (CHK2-/-) HCT116 cells. Accordingly, several HuR-interacting mRNAs encoding apoptosis-and proliferation-related proteins (TJP1, Mdm2, TP53BP2, Bax, K-Ras) dissociated from HuR in WT cells, but remained bound and showed altered post-transcriptional regulation in CHK2-/- cells. Use of HuR mutants that were not phosphorylatable by Chk2 (HuR(3A)) and HuR mutants mimicking constitutive phosphorylation by Chk2 (HuR(3D)) revealed that dissociation of HuR target transcripts enhanced cell survival. We propose that the release of HuR-bound mRNAs via an IR-Chk2-HuR regulatory axis improves cell outcome following IR. The EMBO Journal (2011) 30, 1040-1053. doi:10.1038/emboj.2011.24; Published online 11 February 2011 C1 [Gorospe, Myriam] NIA, Lab Mol Biol & Immunol, IRP, NIH, Baltimore, MD 21224 USA. [Lehrmann, Elin; Zhang, Yongqing; Becker, Kevin G.] NIA, Res Resources Branch, IRP, NIH, Baltimore, MD 21224 USA. [Wang, Jian-Ying] Baltimore Vet Affairs Med Ctr, Baltimore, MD USA. [Kim, Hyeon Ho] Sungkyunkwan Univ, Sch Med, Samsung Biomed Res Inst, Seoul, South Korea. RP Gorospe, M (reprint author), NIA, Lab Mol Biol & Immunol, IRP, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM myriam-gorospe@nih.gov OI Lehrmann, Elin/0000-0002-9869-9475; srikantan, subramanya/0000-0003-1810-6519; abdelmohsen, Kotb/0000-0001-6240-5810; Becker, Kevin/0000-0002-6794-6656 FU National Institute on Aging, National Institutes of Health FX This research was funded by the Intramural Research Program of the National Institute on Aging, National Institutes of Health. We thank A Lohani for his assistance with the irradiation experiments. NR 65 TC 43 Z9 43 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD MAR 16 PY 2011 VL 30 IS 6 BP 1040 EP 1053 DI 10.1038/emboj.2011.24 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 752ER UT WOS:000289672900009 PM 21317874 ER PT J AU Yi, KD Perez, E Yang, SH Liu, R Covey, DF Simpkins, JW AF Yi, Kun Don Perez, Evelyn Yang, Shaohua Liu, Ran Covey, Douglas F. Simpkins, James W. TI The assessment of non-feminizing estrogens for use in neuroprotection SO BRAIN RESEARCH LA English DT Article; Proceedings Paper CT Workshop on Window of Opportunity CY JAN 15-17, 2010 CL Stanford Univ, Stanford, CA HO Stanford Univ DE Estradiol; Estrone; Estrogen; Estratrienes; Neuroprotection; Estrogen receptor; Phenolic A ring; Structure-activity relationship; Middle cerebral artery occlusion ID TRANSIENT FOREBRAIN ISCHEMIA; CEREBRAL-ARTERY OCCLUSION; AMYLOID (25-35)-INDUCED TOXICITY; POSTMENOPAUSAL HORMONE-THERAPY; TOTAL ANTIOXIDATIVE ACTIVITIES; CORONARY-HEART-DISEASE; 17 ALPHA-ESTRADIOL; REPLACEMENT THERAPY; IN-VITRO; HIPPOCAMPAL-NEURONS AB Menopause is associated with a precipitous decline in circulating estrogens and a resulting loss of the neuroprotective actions of this steroid hormone. In view of the results of the Women's Health Initiative and the preceding knowledge that orally administered estrogens has a variety of adverse side effects, likely through actions on peripheral estrogen receptor alpha (ER alpha), we initiated a program of research to synthesis and assess a group of non-feminizing estrogens that lack ability to interact with ERs but retain much of the neuroprotective action of feminizing estrogens. This program of research is aimed at the identification of compounds which do not stimulate ERs but are potentially neuroprotective in vitro and in animal models of neuronal cell death. We discovered that the most effective non-feminizing estrogens were those with large bulky groups in the 2 and/or 4 carbon of the phenolic A ring of the steroid. These compounds were 8- to 114-fold more potent than 17 beta-estradiol (beta E2), but lacked ER binding capacity in vitro and feminizing effects in vivo. The success of this program of research suggests that strategies to optimize non-feminizing estrogens for use in postmenopausal women can be successful. (C) 2010 Elsevier B.V. All rights reserved. C1 [Yi, Kun Don; Yang, Shaohua; Liu, Ran; Simpkins, James W.] Univ N Texas Hlth Sci Ctr, Dept Pharmacol & Neurosci, Inst Aging & Alzheimers Dis Res, Ft Worth, TX 76107 USA. [Perez, Evelyn] NIA, Lab Expt Gerontol, Neurocognit Aging Sect, Baltimore, MD 21224 USA. [Covey, Douglas F.] Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO USA. RP Simpkins, JW (reprint author), Univ N Texas Hlth Sci Ctr, Dept Pharmacol & Neurosci, Inst Aging & Alzheimers Dis Res, Room RES-334J,3500 Camp Bowie Bvld, Ft Worth, TX 76107 USA. EM jsimpkin@hsc.unt.edu RI Yang, Shaohua/D-1738-2013 FU NIA NIH HHS [P01 AG10485, P01 AG022550-07, P01 AG22550, P01 AG010485-18, P01 AG010485, P01 AG022550, P01 AG027956, P01 AG027956-03, P01 AG27956] NR 79 TC 14 Z9 14 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAR 16 PY 2011 VL 1379 SI SI BP 61 EP 70 DI 10.1016/j.brainres.2010.11.058 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 741DW UT WOS:000288844300008 PM 21111714 ER PT J AU Maki, PM Dennerstein, L Clark, M Guthrie, J LaMontagne, P Fornelli, D Little, D Henderson, VW Resnick, SM AF Maki, Pauline M. Dennerstein, Lorraine Clark, Margaret Guthrie, Janet LaMontagne, Pamela Fornelli, Deanne Little, Deborah Henderson, Victor W. Resnick, Susan M. TI Perimenopausal use of hormone therapy is associated with enhanced memory and hippocampal function later in life SO BRAIN RESEARCH LA English DT Article; Proceedings Paper CT Workshop on Window of Opportunity CY JAN 15-17, 2010 CL Stanford Univ, Stanford, CA HO Stanford Univ DE Hormone therapy; Estrogen; Memory; fMRI; Hippocampus; Menopause ID ESTROGEN REPLACEMENT THERAPY; SURGICALLY MENOPAUSAL WOMEN; CEREBRAL-BLOOD-FLOW; POSTMENOPAUSAL WOMEN; NEUROPSYCHOLOGICAL BATTERY; COGNITIVE FUNCTION; AUSTRALIAN WOMEN; PLUS PROGESTIN; MIDLIFE WOMEN; BRAIN VOLUMES AB Evidence suggests that initiation of some forms of hormone therapy (HT) early in the perimenopausal or postmenopausal stage might confer benefit to verbal memory and the neural systems underlying memory, whereas late-life initiation confers no benefit or harm. This "critical window hypothesis" remains a topic of debate. Using functional magnetic resonance imaging (fMRI), we examined the long-term impact of perimenopausal HT use on brain function during performance of verbal and figural memory tasks. Participants were 34 postmenopausal women (mean age 60 years) from the Melbourne Women's Midlife Health Project and included 17 early (perimenopausal) and continuous users of HT and 17 never users matched on age, education, and verbal knowledge. Continuous HT use from the perimenopausal stage versus no use was validated with prospective daily diary records and study visit data. The primary outcome was patterns of brain activation in an a priori region of interest in the medial temporal lobe during verbal encoding and recognition of words. Results indicated that perimenopausal HT users performed better than nonusers on the imaging verbal memory task (p<.05). During verbal recognition, perimenopausal HT users showed increased activation in the left hippocampus and decreased activation in the parahippocampal gyrus bilaterally compared with never users. Each of these patterns of activation was associated with better memory performance on the imaging memory task. These results suggest that perimenopausal use of HT might confer long-term benefits to verbal memory and the brain systems underlying verbal memory. More generally, the results support the critical window hypothesis. (C) 2010 Elsevier B.V. All rights reserved. C1 [Maki, Pauline M.; LaMontagne, Pamela; Fornelli, Deanne] Univ Illinois, Dept Psychiat, Neuropsychiat Inst MC 913, Chicago, IL 60612 USA. [Maki, Pauline M.] Univ Illinois, Dept Psychol, Chicago, IL 60607 USA. [Dennerstein, Lorraine; Clark, Margaret; Guthrie, Janet] Univ Melbourne, Dept Psychiat, Off Gender & Hlth, Melbourne, Vic 3010, Australia. [Dennerstein, Lorraine; Clark, Margaret; Guthrie, Janet] Univ Melbourne, Dept Psychiat, Natl Ageing Res Inst, Melbourne, Vic 3010, Australia. [Little, Deborah] Dept Neurol & Rehabil MC 796, Chicago, IL 60612 USA. [Henderson, Victor W.] Stanford Univ, Dept Hlth Res & Policy Epidemiol, Stanford, CA 94305 USA. [Henderson, Victor W.] Stanford Univ, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA. [Resnick, Susan M.] NIA, Lab Personal & Cognit, Biomed Res Ctr, Baltimore, MD 21224 USA. RP Maki, PM (reprint author), Univ Illinois, Dept Psychiat, Neuropsychiat Inst MC 913, 912 S Wood St, Chicago, IL 60612 USA. EM pmaki@psych.uic.edu; lorrdenn@aol.com; msclark@unimelb.edu.au; janetrg@unimelb.edu.au; pperschler@gmail.com; deanne.fornelli@gmail.com; little@uic.edu; vhenderson@stanford.edu; resnicks@grc.nia.nih.gov FU Intramural NIH HHS [Z99 AG999999] NR 43 TC 48 Z9 48 U1 0 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAR 16 PY 2011 VL 1379 SI SI BP 232 EP 243 DI 10.1016/j.brainres.2010.11.030 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 741DW UT WOS:000288844300023 PM 21078303 ER PT J AU Castano-Vinyals, G Cantor, KP Villanueva, CM Tardon, A Garcia-Closas, R Serra, C Carrato, A Malats, N Rothman, N Silverman, D Kogevinas, M AF Castano-Vinyals, Gemma Cantor, Kenneth P. Villanueva, Cristina M. Tardon, Adonina Garcia-Closas, Reina Serra, Consol Carrato, Alfredo Malats, Nuria Rothman, Nathaniel Silverman, Debra Kogevinas, Manolis TI Socioeconomic status and exposure to disinfection by-products in drinking water in Spain SO ENVIRONMENTAL HEALTH LA English DT Article ID ENVIRONMENTAL EQUITY; AIR-POLLUTION; HEALTH-STATUS; SOCIAL-CLASS; RACE; TRIHALOMETHANES; CANCER AB Background: Disinfection by-products in drinking water are chemical contaminants that have been associated with cancer and other adverse effects. Exposure occurs from consumption of tap water, inhalation and dermal absorption. Methods: We determined the relationship between socioeconomic status and exposure to disinfection by-products in 1271 controls from a multicentric bladder cancer case-control study in Spain. Information on lifetime drinking water sources, swimming pool attendance, showering-bathing practices, and socioeconomic status (education, income) was collected through personal interviews. Results: The most highly educated subjects consumed less tap water (57%) and more bottled water (33%) than illiterate subjects (69% and 17% respectively, p-value = 0.003). These differences became wider in recent time periods. The time spent bathing or showering was positively correlated with attained educational level (p < 0.001). Swimming pool attendance was more frequent among highly educated subjects compared to the illiterate (odds ratio = 3.4; 95% confidence interval 1.6-7.3). Conclusions: The most highly educated subjects were less exposed to chlorination by-products through ingestion but more exposed through dermal contact and inhalation in pools and showers/baths. Health risk perceptions and economic capacity may affect patterns of water consumption that can result in differences in exposure to water contaminants. C1 [Castano-Vinyals, Gemma; Villanueva, Cristina M.; Kogevinas, Manolis] Ctr Res Environm Epidemiol CREAL, Barcelona, Spain. [Castano-Vinyals, Gemma; Villanueva, Cristina M.; Kogevinas, Manolis] IMIM Hosp Mar, Municipal Inst Med Res, Barcelona, Spain. [Castano-Vinyals, Gemma; Villanueva, Cristina M.; Tardon, Adonina; Kogevinas, Manolis] CIBER Epidemiol Salud Publ CIBERESP, Barcelona, Spain. [Cantor, Kenneth P.; Rothman, Nathaniel; Silverman, Debra] NCI, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Tardon, Adonina] Univ Oviedo, Oviedo, Spain. [Garcia-Closas, Reina] Hosp Univ Canarias La Laguna, Unidad Invest, Tenerife, Spain. Univ Pompeu Fabra, Barcelona, Spain. [Serra, Consol] Consorci Hosp Parc Tauli, Sabadell, Spain. [Carrato, Alfredo] Hosp Gen Elche, Elche, Spain. [Malats, Nuria] Ctr Nacl Invest Oncol CNIO, Madrid, Spain. [Kogevinas, Manolis] Univ Crete, Sch Med, Dept Social Med, Iraklion, NE, Greece. RP Castano-Vinyals, G (reprint author), Ctr Res Environm Epidemiol CREAL, Barcelona, Spain. EM gcastano@creal.cat RI Serra, C/E-6879-2014; Malats, Nuria/H-7041-2015; Villanueva, Cristina/N-1942-2014; Kogevinas, Manolis/C-3918-2017; OI Serra, C/0000-0001-8337-8356; Malats, Nuria/0000-0003-2538-3784; Villanueva, Cristina/0000-0002-0783-1259; Castano-Vinyals, Gemma/0000-0003-4468-1816 FU National Institutes of Health, National Cancer Institute (NCI); Division of Cancer Epidemiology and Genetics, NCI Westat [N02 CP-11015, FIS/Spain 00/0745, G03/174, PI061614, CA34627]; Red Tematica de Investigacion Cooperativa en Cancer (RTICC); Instituto de Salud Carlos III, Spanish Ministry of Health and Consumption [CP06/00341] FX We thank Mustafa Dosemeci for his important role in the organizing the initial stages of this study. We thank Robert C. Saal from Westat, Rockville, MD, Leslie Carroll and Eric Boyd from IMS, Silver Spring, MD, and Paco Fernandez, IMIM, Barcelona, for their support in study and data management; Dr. Maria Sala from IMIM, Barcelona, for her work in data collection; physicians, nurses, interviewers (Ana Alfaro, Cristina Villanueva, Cristina Pipo, Joan Montes, Iolanda Velez, Pablo Hernandez, Angeles Perez, Carmen Benito, Adela Castillejo, Elisa Jover, Natalia Blanco, Avelino Menendez, Cristina Arias, Begona Arguelles) and all participants in the study for their efforts during field work. This work was supported by the Intramural Program of the National Institutes of Health, National Cancer Institute (NCI), Division of Cancer Epidemiology and Genetics, NCI Westat contract no. N02 CP-11015, FIS/Spain 00/0745, G03/174, PI061614, CA34627, and Red Tematica de Investigacion Cooperativa en Cancer (RTICC). Cristina M Villanueva has a contract funded by the Instituto de Salud Carlos III, Spanish Ministry of Health and Consumption (CP06/00341). NR 18 TC 8 Z9 8 U1 0 U2 18 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1476-069X J9 ENVIRON HEALTH-GLOB JI Environ. Health PD MAR 16 PY 2011 VL 10 AR 18 DI 10.1186/1476-069X-10-18 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 742RS UT WOS:000288962800001 PM 21410938 ER PT J AU Tuo, WB Zhao, Y Zhu, DM Jenkins, MC AF Tuo, Wenbin Zhao, Yan Zhu, Daming Jenkins, Mark C. TI Immunization of female BALB/c mice with Neospora cyclophilin and/or NcSRS2 elicits specific antibody response and prevents against challenge infection by Neospora caninum SO VACCINE LA English DT Article DE Neospora caninum; NcCyP; Cyclophilin; Vaccine; Neosporosis ID RECOMBINANT VACCINIA VIRUS; REDUCED CEREBRAL INFECTION; VERTICAL TRANSMISSION; IMMUNE-RESPONSES; SURFACE PROTEIN; TOXOPLASMA-GONDII; C57BL/6 MICE; PREGNANT CATTLE; N-CANINUM; VACCINATION AB Neospora caninum is the causal agent of bovine neosporosis which results in high levels of abortion. The present study determined the protective efficacy of two Neospora antigens - Neospora cyclophilin (NcCyP) and NcSRS2. The ability of native NcCyP to upregulate mouse IFN-gamma was also confirmed in this study. Recombinant NcCyP or NcSRS2 were tested either alone or in combination and formulated with adjuvant ImmuMax-SR and CpG. Female BALB/c mice (n = 15) of 10-12 weeks of age were immunized s.c. twice over a 2-week interval with vaccines containing either NcCyP (20 mu g/dose) alone, NcSRS2 (20 mu g/dose) alone, NcCyP plus NcSRS2, or non-recombinant bacterial antigen (NR) in 2 separate trials. All mice were challenge-infected 3 weeks following the booster immunization and necropsied 3 weeks after the challenge infection. Brain and serum were collected and Nc-specific DNA sequence in brain tissue and antibodies in serum were analyzed by PCR or ELISA/Western blotting. Results showed that mice vaccinated with rNcCyP, rNcSRS2, or both rNcCyP and rNcSRS2 responded with high levels of NcCyP or NcSRS2 specific antibodies. Overall, mice received vaccines formulated with either rNcCyP or rNcCyP and rNcSRS2 had a higher (p < 0.01) percent protection when compared to the mock- or non-vaccinated mice. The group immunized with rNcSRS2 alone exhibited slightly lower levels of protection, which was higher (p <0.05) than that of the non-vaccinated group but did not differ (p = 0.06) from that of the mock-vaccinated group. The results of the present study indicate that NcCyP is a highly efficacious vaccine candidate which may be useful in protection against Neospora infection. Published by Elsevier Ltd. C1 [Tuo, Wenbin; Jenkins, Mark C.] USDA ARS, Anim Parasit Dis Lab, Beltsville Agr Res Ctr, Beltsville, MD 20705 USA. [Zhao, Yan] USDA ARS, Mol Plant Pathol Lab, Beltsville Agr Res Ctr, Beltsville, MD 20705 USA. [Zhu, Daming] NIAID, Qual Control Unit, NIH, Rockville, MD 20852 USA. RP Tuo, WB (reprint author), USDA ARS, Anim Parasit Dis Lab, Beltsville Agr Res Ctr, Beltsville, MD 20705 USA. EM wenbin.tuo@ars.usda.gov FU Ministry of Education, P.R. China FX The authors would like to thank Dr. Celia O'Brien, Ms. Carolyn Parker and Mr. Eli Miramontes for technical assistance. Wenbin Tuo is an adjunct faculty of the College of Animal Science and Veterinary Medicine, Jilin University, Changchun, China and sponsored by the "Overseas Cultural and Educational Expert" program of the Ministry of Education, P.R. China.- NR 52 TC 9 Z9 10 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAR 16 PY 2011 VL 29 IS 13 BP 2392 EP 2399 DI 10.1016/j.vaccine.2011.01.041 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 745CC UT WOS:000289140500008 PM 21281689 ER PT J AU Landgren, O Waxman, AJ Korde, N AF Landgren, Ola Waxman, Adam Justin Korde, Neha TI Progression From Precursor Disease to Multiple Myeloma Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID UNDETERMINED SIGNIFICANCE MGUS; MONOCLONAL GAMMOPATHY C1 [Landgren, Ola; Waxman, Adam Justin; Korde, Neha] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. RP Landgren, O (reprint author), NCI, Med Oncol Branch, Bethesda, MD 20892 USA. EM landgreo@mail.nih.gov NR 4 TC 0 Z9 0 U1 0 U2 1 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 MAR 16 PY 2011 VL 305 IS 11 BP 1094 EP 1094 DI 10.1001/jama.2011.302 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 734ZF UT WOS:000288381900016 ER PT J AU Genovesio, A Tsujimoto, S Wise, SP AF Genovesio, Aldo Tsujimoto, Satoshi Wise, Steven P. TI Prefrontal Cortex Activity during the Discrimination of Relative Distance SO JOURNAL OF NEUROSCIENCE LA English DT Article ID POSTERIOR PARIETAL CORTEX; BABOONS PAPIO-PAPIO; ORBITOFRONTAL CORTEX; NEURONAL-ACTIVITY; WORKING-MEMORY; RETINAL DISPARITY; SPATIAL RELATIONS; TEMPORAL-ORDER; FRONTAL-CORTEX; UNIT-ACTIVITY AB To compare with our previous findings on relative-duration discrimination, we studied prefrontal cortex activity as monkeys performed a relative-distance discrimination task. We wanted to know whether the same parts of the prefrontal cortex compare durations and distances and, if so, whether they use similar mechanisms. Two stimuli appeared sequentially on a video screen, one above a fixed reference point, the other below it by a different distance. After a delay period, the same two stimuli reappeared (as choice stimuli), and the monkeys' task was to choose the one that had appeared farther from the reference point during its initial presentation. We recorded from neurons in the dorsolateral prefrontal cortex (area 46) and the caudal prefrontal cortex (area 8). Although some prefrontal neurons encoded the absolute distance of a stimulus from the reference point, many more encoded relative distance. Categorical representations ("farther") predominated over parametric ones ("how much farther"). Relative-distance coding was most often abstract, coding the farther or closer stimulus to the same degree, independent of its position on the screen. During the delay period before the choice stimuli appeared, feature-based coding supplanted order-based coding, and position-based coding-always rare-decreased to chance levels. The present results closely resembled those for a duration-discrimination task in the same cortical areas. We conclude, therefore, that these areas contribute to decisions based on both spatial and temporal information. C1 [Genovesio, Aldo] Univ Rome, Dept Physiol & Pharmacol, I-00185 Rome, Italy. [Genovesio, Aldo; Tsujimoto, Satoshi; Wise, Steven P.] NIMH, Lab Syst Neurosci, Bethesda, MD 20892 USA. [Tsujimoto, Satoshi] Kobe Univ, Grad Sch Human Dev & Environm, Dev Cognit Neurosci Lab, Kobe, Hyogo 6578501, Japan. RP Genovesio, A (reprint author), Univ Rome, Dept Physiol & Pharmacol, Piazzale Aldo Moro 5, I-00185 Rome, Italy. EM aldo.genovesio@uniroma1.it RI Tsujimoto, Satoshi/B-8223-2011 FU Division of Intramural Research of the National Institute of Mental Health [Z01MH-01092] FX This work was supported by Division of Intramural Research of the National Institute of Mental Health Grant Z01MH-01092. We thank Dr. Andrew Mitz, James Fellows, and Ping-Yu Chen for technical support. NR 66 TC 27 Z9 27 U1 1 U2 3 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 MAR 16 PY 2011 VL 31 IS 11 BP 3968 EP 3980 DI 10.1523/JNEUROSCI.5373-10.2011 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 735YC UT WOS:000288455700007 PM 21411640 ER PT J AU Guez-Barber, D Fanous, S Golden, SA Schrama, R Koya, E Stern, AL Bossert, JM Harvey, BK Picciotto, MR Hope, BT AF Guez-Barber, Danielle Fanous, Sanya Golden, Sam A. Schrama, Regina Koya, Eisuke Stern, Anna L. Bossert, Jennifer M. Harvey, Brandon K. Picciotto, Marina R. Hope, Bruce T. TI FACS Identifies Unique Cocaine-Induced Gene Regulation in Selectively Activated Adult Striatal Neurons SO JOURNAL OF NEUROSCIENCE LA English DT Article ID CONTEXT-SPECIFIC SENSITIZATION; INDUCED LOCOMOTOR-ACTIVITY; LONG-TERM PLASTICITY; FOS MESSENGER-RNA; NUCLEUS-ACCUMBENS; RECEPTOR ACTIVATION; MOLECULAR-BASIS; SPINY NEURONS; EXPRESSION; INDUCTION AB Numerous studies with the neural activity marker Fos indicate that cocaine activates only a small proportion of sparsely distributed striatal neurons. Until now, efficient methods were not available to assess neuroadaptations induced specifically within these activated neurons. We used fluorescence-activated cell sorting (FACS) to purify striatal neurons activated during cocaine-induced locomotion in naive and cocaine-sensitized cfos-lacZ transgenic rats. Activated neurons were labeled with an antibody against beta-galactosidase, the protein product of the lacZ gene. Cocaine induced a unique gene expression profile selectively in the small proportion of activated neurons that was not observed in the nonactivated majority of neurons. These genes included altered levels of the immediate early genes arc, fosB, and nr4a3, as well as genes involved in p38 MAPK signaling and cell-type specificity. We propose that this FACS method can be used to study molecular neuroadaptations in specific neurons encoding the behavioral effects of abused drugs and other learned behaviors. C1 [Guez-Barber, Danielle; Fanous, Sanya; Golden, Sam A.; Schrama, Regina; Koya, Eisuke; Stern, Anna L.; Bossert, Jennifer M.; Hope, Bruce T.] NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. [Harvey, Brandon K.] NIDA, Mol Neuropsychiat Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. [Guez-Barber, Danielle; Picciotto, Marina R.] Yale Univ, Sch Med, Interdept Neurosci Program, New Haven, CT 06515 USA. [Picciotto, Marina R.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06515 USA. RP Hope, BT (reprint author), NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM bhope@intra.nida.nih.gov RI Picciotto, Marina/F-8747-2012; Hope, Bruce/A-9223-2010; OI Picciotto, Marina/0000-0002-4404-1280; Hope, Bruce/0000-0001-5804-7061; Golden, Sam/0000-0002-2104-2272 FU National Institute on Drug Abuse [F30DA024931]; National Institutes of Health [TG 5T32GM07205]; Charles B. G. Murphy Chair in Psychiatry at Yale University FX This research was supported by the Intramural Research Program of the National Institute on Drug Abuse. D.G.-B. was supported by National Institutes of Health Medical Scientist Training Program TG 5T32GM07205, Award Number F30DA024931 from the National Institute on Drug Abuse, and the Charles B. G. Murphy Chair in Psychiatry at Yale University. We thank Joe Chrest for his excellent technical assistance with FACS, and Chris Cheadle, Tonya Watkins, and Alan Berger for their work on the microarray. We thank Yavin Shaham for helpful comments on the manuscript. NR 37 TC 33 Z9 35 U1 0 U2 3 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 MAR 16 PY 2011 VL 31 IS 11 BP 4251 EP 4259 DI 10.1523/JNEUROSCI.6195-10.2011 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 735YC UT WOS:000288455700033 PM 21411666 ER PT J AU Parthasarathy, S Long, F Miller, Y Xiao, YL McElheny, D Thurber, K Ma, BY Nussinov, R Ishii, Y AF Parthasarathy, Sudhakar Long, Fei Miller, Yifat Xiao, Yiling McElheny, Dan Thurber, Kent Ma, Buyong Nussinov, Ruth Ishii, Yoshitaka TI Molecular-Level Examination of Cu2+ Binding Structure for Amyloid Fibrils of 40-Residue Alzheimer's beta by Solid-State NMR Spectroscopy SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; M2 PROTON CHANNELS; A-BETA; SUPEROXIDE-DISMUTASE; DYNAMICS SIMULATIONS; ZINC-BINDING; EXPERIMENTAL CONSTRAINTS; PARAMAGNETIC-COMPLEXES; DISTANCE MEASUREMENTS; SECONDARY-STRUCTURE AB Cu2+ binding to Alzheimer's beta (A beta) peptides in amyloid fibrils has attracted broad attention, as it was shown that Cu ion concentration elevates in Alzheimer's senile plaque and such association of A beta with Cu2+ triggers the production of neurotoxic reactive oxygen species (ROS) such as H2O2. However, detailed binding sites and binding structures of Cu2+ to A beta are still largely unknown for A beta fibrils or other aggregates of A beta In this work, we examined molecular details of Cu2+ binding to amyloid fibrils by detecting paramagnetic signal quenching in ID and 2D high-resolution C-13 solid-state NMR (SSNMR) for full-length 40-residue A beta(1-40). Selective quenching observed in C-13 SSNMR of Cu2+-bound A beta(1-40) suggested that primary Cu2+ binding sites in A beta(1-40) fibrils include N-epsilon in His-13 and His-14 and carboxyl groups in Val-40 as well as in Glu sidechains (Glu-3, Glu-11, and/or Glu-22). C-13 chemical shift analysis demonstrated no major structural changes upon Cu2+ binding in the hydrophobic core regions (residues 18-25 and 30-36). Although the ROS production via oxidization of Met-35 in the presence of Cu2+ has been long suspected, our SSNMR analysis of (C epsilon H3)-C-13-S- in M35 showed little changes after Cu2+ binding, excluding the possibility of Met-35 oxidization by Cu2+ alone. Preliminary molecular dynamics (MD) simulations on Cu2+ A beta complex in amyloid fibrils confirmed binding sites suggested by the SSNMR results and the stabilities of such bindings. The MD simulations also indicate the coexistence of a variety of Cu2+-binding modes unique in A beta fibril, which are realized by both intra- and intermolecular contacts and highly concentrated coordination sites due to the in-register parallel A beta-sheet arrangements. C1 [Parthasarathy, Sudhakar; Long, Fei; Xiao, Yiling; McElheny, Dan; Ishii, Yoshitaka] Univ Illinois, Dept Chem, Chicago, IL 60607 USA. [Ma, Buyong; Nussinov, Ruth] NCI, Basic Res Program, SAIC Frederick Inc, Ctr Canc Res,Nanobiol Program, Frederick, MD 21702 USA. [Thurber, Kent] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. [Nussinov, Ruth] Tel Aviv Univ, Dept Human Genet & Mol Med, Sackler Inst Mol Med, Sackler Sch Med, IL-69978 Tel Aviv, Israel. RP Ishii, Y (reprint author), Univ Illinois, Dept Chem, Chicago, IL 60607 USA. EM yishii@uic.edu RI Ma, Buyong/F-9491-2011; Ishii, Yoshitaka/F-4558-2014 OI Ma, Buyong/0000-0002-7383-719X; Ishii, Yoshitaka/0000-0002-7724-6469 FU NIH [AG028490, HHSN261200800001E]; Alzheimer's Association [IIRG 08-91256]; NSF [CHE 449952, CHE 957793]; Dreyfus Foundation; NCI FX This study was supported primarily by NIH ROI program (AG028490) and the Alzheimer's Association grant (IIRG 08-91256). The SSNMR methodology development in this work was also supported by the NSF (CHE 449952, CHE 957793) and the Dreyfus Foundation Teacher-Scholar Award program. This project has been funded in part with Federal funds from the NCI, NIH, under contract number HHSN261200800001E. Simulations were also performed on the Biowulf cluster at the NIH (http://biowulf.nih.gov). We thank Dr. Robert Tycko at the NIH for providing a pdb file of the structural model for A beta(1-40) fibril and the A beta fibrils samples used for Figure S3 in the SI. We are also grateful to Prof. Michael Zagorski at Case Western Reserve University for kind clarifications on his works. NR 103 TC 106 Z9 107 U1 0 U2 71 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD MAR 16 PY 2011 VL 133 IS 10 BP 3390 EP 3400 DI 10.1021/ja1072178 PG 11 WC Chemistry, Multidisciplinary SC Chemistry GA 735JK UT WOS:000288410100039 PM 21341665 ER EF