FN Thomson Reuters Web of Science™
VR 1.0
PT B
AU Xie, J
Gao, JH
Michalski, M
Chen, XY
AF Xie, Jin
Gao, Jinhao
Michalski, Mark
Chen, Xiaoyuan
BE Chen, X
TI Nanoparticle Surface Modification and Bioconjugation
SO NANOPLATFORM-BASED MOLECULAR IMAGING
LA English
DT Article; Book Chapter
ID WALLED CARBON NANOTUBES; SEMICONDUCTOR QUANTUM DOTS; IRON-OXIDE
NANOPARTICLES; RESONANCE ENERGY-TRANSFER; NONCOVALENT
SIDEWALL-FUNCTIONALIZATION; MESOPOROUS SILICA NANOPARTICLES;
DIIMIDE-ACTIVATED AMIDATION; MAGNETIC NANOPARTICLES; IN-VIVO; BIOMEDICAL
APPLICATIONS
C1 [Xie, Jin; Gao, Jinhao; Michalski, Mark; Chen, Xiaoyuan] Stanford Univ, Sch Med, Dept Radiol, Mol Imaging Program Stanford, Stanford, CA 94305 USA.
[Xie, Jin; Gao, Jinhao; Michalski, Mark; Chen, Xiaoyuan] Stanford Univ, Sch Med, Dept Radiol, Bio X Program, Stanford, CA 94305 USA.
[Xie, Jin; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD USA.
RP Xie, J (reprint author), Stanford Univ, Sch Med, Dept Radiol, Mol Imaging Program Stanford, Stanford, CA 94305 USA.
NR 149
TC 1
Z9 1
U1 1
U2 2
PU BLACKWELL SCIENCE PUBL
PI OXFORD
PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND
BN 978-0-470-76703-0; 978-0-470-52115-1
PY 2011
BP 47
EP 73
D2 10.1002/9780470767047
PG 27
WC Nanoscience & Nanotechnology; Radiology, Nuclear Medicine & Medical
Imaging
SC Science & Technology - Other Topics; Radiology, Nuclear Medicine &
Medical Imaging
GA BA5SW
UT WOS:000336989900004
ER
PT B
AU Zabow, G
Koretsky, A
AF Zabow, Gary
Koretsky, Alan
BE Chen, X
TI Microfabricated Multispectral MRI Contrast Agents
SO NANOPLATFORM-BASED MOLECULAR IMAGING
LA English
DT Article; Book Chapter
ID SUPERPARAMAGNETIC IRON-OXIDE; RESONANCE-IMAGING MEMRI; SINGLE
MAMMALIAN-CELLS; MAGNETIC-RESONANCE; IN-VIVO; CELLULAR MRI; STEM-CELLS;
PROTON-EXCHANGE; PARACEST AGENTS; RODENT BRAIN
C1 [Zabow, Gary; Koretsky, Alan] NINCDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
RP Zabow, G (reprint author), NINCDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
RI Koretsky, Alan/C-7940-2015
OI Koretsky, Alan/0000-0002-8085-4756
NR 82
TC 0
Z9 0
U1 0
U2 1
PU BLACKWELL SCIENCE PUBL
PI OXFORD
PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND
BN 978-0-470-76703-0; 978-0-470-52115-1
PY 2011
BP 375
EP 397
D2 10.1002/9780470767047
PG 23
WC Nanoscience & Nanotechnology; Radiology, Nuclear Medicine & Medical
Imaging
SC Science & Technology - Other Topics; Radiology, Nuclear Medicine &
Medical Imaging
GA BA5SW
UT WOS:000336989900017
ER
PT J
AU Bhirde, A
Xie, J
Swierczewska, M
Chen, XY
AF Bhirde, Ashwinkumar
Xie, Jin
Swierczewska, Maggie
Chen, Xiaoyuan
TI Nanoparticles for cell labeling
SO NANOSCALE
LA English
DT Article
ID IRON-OXIDE NANOPARTICLES; MESENCHYMAL STEM-CELLS; REPORTER
GENE-EXPRESSION; MRI CONTRAST AGENTS; IN-VIVO TRACKING; QUANTUM DOTS;
MAGNETIC-RESONANCE; TRANSPLANTED CELLS; LIVE CELL; INORGANIC
NANOPARTICLES
AB Cell based therapeutics are emerging as powerful regimens. To better understand the migration and proliferation mechanisms of implanted cells, a means to track cells in living subjects is essential, and to achieve that, a number of cell labeling techniques have been developed. Nanoparticles, with their superior physical properties, have become the materials of choice in many investigations along this line. Owing to inherent magnetic, optical or acoustic attributes, these nanoparticles can be detected by corresponding imaging modalities in living subjects at a high spatial and temporal resolution. These features allow implanted cells to be separated from host cells; and have advantages over traditional histological methods, as they permit non-invasive, real-time tracking in vivo. This review attempts to give a summary of progress in using nanotechnology to monitor cell trafficking. We will focus on direct cell labeling techniques, in which cells ingest nanoparticles that bear traceable signals, such as iron oxide or quantum dots. Ferritin and MagA reporter genes that can package endogenous iron or iron supplement into iron oxide nanoparticles will also be discussed.
C1 [Bhirde, Ashwinkumar; Xie, Jin; Swierczewska, Maggie; Chen, Xiaoyuan] NIBIB, LOMIN, NIH, Bethesda, MD 20892 USA.
RP Chen, XY (reprint author), NIBIB, LOMIN, NIH, Bethesda, MD 20892 USA.
EM shawn.chen@nih.gov
RI Xie, Jin/E-8193-2010
FU NIH, National Institute of Biomedical Imaging and Bioengineering
FX This research was supported by the Intramural Research Program of the
NIH, including the National Institute of Biomedical Imaging and
Bioengineering.
NR 155
TC 115
Z9 117
U1 5
U2 52
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 2040-3364
J9 NANOSCALE
JI Nanoscale
PY 2011
VL 3
IS 1
BP 142
EP 153
DI 10.1039/c0nr00493f
PG 12
WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials
Science, Multidisciplinary; Physics, Applied
SC Chemistry; Science & Technology - Other Topics; Materials Science;
Physics
GA 706FY
UT WOS:000286204600011
PM 20938522
ER
PT J
AU Xing, RJ
Zhang, F
Xie, J
Aronova, M
Zhang, GF
Guo, N
Huang, XL
Sun, XL
Liu, G
Bryant, LH
Bhirde, A
Liang, A
Hou, YL
Leapman, RD
Sun, SH
Chen, XY
AF Xing, Ruijun
Zhang, Fan
Xie, Jin
Aronova, Maria
Zhang, Guofeng
Guo, Ning
Huang, Xinglu
Sun, Xiaolian
Liu, Gang
Bryant, L. Henry
Bhirde, Ashwinkumar
Liang, Amy
Hou, Yanglong
Leapman, Richard D.
Sun, Shouheng
Chen, Xiaoyuan
TI Polyaspartic acid coated manganese oxide nanoparticles for efficient
liver MRI
SO NANOSCALE
LA English
DT Article
ID MAGNETIC NANOPARTICLES; MNO NANOPARTICLES; FUNCTIONALIZATION; DELIVERY;
CONTRAST; CANCER
AB We report in this communication a simple, facile surface modification strategy to transfer hydrophobic manganese oxide nanoparticles (MONPs) into water by using polyaspartic acid (PASP). We systematically investigated the effect of the size of PASP-MONPs on MRI of normal liver and found that the particles with a core size of 10 nm exhibited greater enhancement than those with larger core sizes.
C1 [Xing, Ruijun; Zhang, Fan; Xie, Jin; Guo, Ning; Huang, Xinglu; Liu, Gang; Liang, Amy; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA.
[Xing, Ruijun; Bhirde, Ashwinkumar; Hou, Yanglong] Peking Univ, Coll Engn, Dept Mat Sci & Engn, Beijing 100871, Peoples R China.
[Aronova, Maria; Zhang, Guofeng; Leapman, Richard D.] NIBIB, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA.
[Sun, Xiaolian; Sun, Shouheng] Brown Univ, Dept Chem, Providence, RI 02912 USA.
[Bryant, L. Henry] NIH, Lab Diagnost Radiol Res CC, Bethesda, MD 20892 USA.
RP Chen, XY (reprint author), NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA.
EM shawn.chen@nih.gov
RI Hou, Yanglong/B-8241-2012; Hou, Yanglong/B-8688-2012
FU National Institute of Biomedical Imaging and Bioengineering (NIBIB), NCI
R00 [CA153772]; National Nature Science of Foundation of China (NSFC)
[51172005, 81028009]; National Basic Research Program of China
[2010CB934602]; China Scholarship Council
FX This research was supported in part by the Intramural Research Program
of the National Institute of Biomedical Imaging and Bioengineering
(NIBIB), an NCI R00 grant CA153772 (to J.X.), the National Nature
Science of Foundation of China (NSFC) (51172005 and 81028009), and the
National Basic Research Program of China (2010CB934602). R.X. is
partially supported by the China Scholarship Council.
NR 14
TC 22
Z9 24
U1 3
U2 37
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 2040-3364
J9 NANOSCALE
JI Nanoscale
PY 2011
VL 3
IS 12
BP 4943
EP 4945
DI 10.1039/c1nr11242b
PG 3
WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials
Science, Multidisciplinary; Physics, Applied
SC Chemistry; Science & Technology - Other Topics; Materials Science;
Physics
GA 855ST
UT WOS:000297585500006
PM 22064945
ER
PT B
AU Kobayashi, H
AF Kobayashi, H.
BE Laudon, M
Romanowicz, B
TI Pharmacokinetics and clearance properties of nano-sized particles and
molecules as multi-modality imaging agents: Considerations and caveats
SO NANOTECHNOLOGY 2011: BIO SENSORS, INSTRUMENTS, MEDICAL, ENVIRONMENT AND
ENERGY, NSTI-NANOTECH 2011, VOL 3
LA English
DT Proceedings Paper
CT NSTI Nanotechnology Conference and Expo
CY JUN 13-16, 2011
CL Boston, MA
SP Clean Technol & Sustainable Ind Org, European Patent Off, Greenberg Traurig, Innovat & Mat Sci Inst, Jackson Walker LLP, Linde Nanomaterials, Lockheed Martin, Nano Sci & Technol Inst, Nano Tech Japan, NanoEurope Fair & Conf, Nanpolis Suzhou, Suzhou Nanotech Co Ltd, Natl Inst Standards & Technol, Ctr Nanoscale Sci & Technol, Fraunhofer, Res Germany, TechConnect, Technol Innovat Program, Canadian Trade Commiss Serv, Italian Trade Commiss
DE nanomaterials; imaging; clearance; nano-toxicology; dendrimer
ID MRI CONTRAST AGENTS; QUANTUM DOTS; CORES; FV
AB Nano-sized particles and molecules possess enormous potential as diagnostic imaging agents and hold promise for the development of multimodality agents with both imaging and therapeutic capabilities. Yet, some of the most promising nano-materials currently under investigation demonstrate prolonged tissue retention and contain heavy metals. This presents serious concerns for toxicity and additionally, prolonged particle retention may interfere with diagnostic imaging and testing modalities. The creation of nano-sized particles and molecules with optimal pharmacokinetics and clearance characteristics will minimize toxicity risks by reducing the duration of exposure to these agents. Given that many types of nano materials possess easily modifiable surface chemistry, if nanoparticle characteristics associated with optimal pharmacokinetics and clearance from the body were well established, it would be feasible to design and create agents with more favorable clearance properties. In this talk, based on our experiences of dendrimer-based nano-sized MRI/Optical/Nuclear multimodality imaging agents, I will discuss the physiologic clearance of nano-sized particle and molecule, especially focusing on renal mechanisms, as well as provides an extended view of current research investigating clearance of other types of nano-sized particles and molecules, including dendrimers, quantum dots, and carbon, gold, and silica-based nanoparticles.
C1 [Kobayashi, H.] NCI, Mol Imaging Program, NIH, Bldg 10,Rm B3B69,10 Ctr Dr, Bethesda, MD 20892 USA.
RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, NIH, Bldg 10,Rm B3B69,10 Ctr Dr, Bethesda, MD 20892 USA.
EM kobayash@mail.nih.gov
NR 19
TC 0
Z9 0
U1 0
U2 0
PU CRC PRESS-TAYLOR & FRANCIS GROUP
PI BOCA RATON
PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA
BN 978-1-4398-7138-6
PY 2011
BP 125
EP 128
PG 4
WC Energy & Fuels; Engineering, Environmental; Nanoscience &
Nanotechnology; Medicine, Research & Experimental; Materials Science,
Biomaterials
SC Energy & Fuels; Engineering; Science & Technology - Other Topics;
Research & Experimental Medicine; Materials Science
GA BG9XC
UT WOS:000394061000034
ER
PT J
AU Ahmed, SB
Sghaier, RM
Guesmi, F
Kaabi, B
Mejri, M
Attia, H
Laouini, D
Smaali, I
AF Ahmed, S. Ben Hadj
Sghaier, R. M.
Guesmi, F.
Kaabi, B.
Mejri, M.
Attia, H.
Laouini, D.
Smaali, I.
TI Evaluation of antileishmanial, cytotoxic and antioxidant activities of
essential oils extracted from plants issued from the
leishmaniasis-endemic region of Sned (Tunisia)
SO NATURAL PRODUCT RESEARCH
LA English
DT Article
DE leishmaniasis; essential oils; antiparasitic; antioxidant; cytotoxicity;
GC-MS
ID CHEMICAL-COMPOSITION; VOLATILE COMPONENTS; CUTANEOUS LEISHMANIASIS;
RUTA-CHALEPENSIS; IN-VITRO; L.; CONSTITUENTS; ANTIBACTERIAL; GROWTH
AB In this study, we tested 10 essential oils (EOs) extracted from 10 plants issued from Sned region (Tunisia) to evaluate both their leishmanicidal effects against Leishmania major and L. infantum, and their cytotoxicity against murine macrophage cell line RAW 264.7 (ATCC, TIB-71). The antioxidant activity was also monitored by the DDPH method, while the chemical composition of active EO was assessed by GC-MS analysis. The results showed that the EOs obtained from Thymus hirtus sp. algeriensis (rich on monoterpenoids, especially linalool at 17.62% and camphor at 13.82%) is significantly active against both L. major and L. infantum, whereas Ruta chalepensis EO (rich on 2-undecanone at 84.28%) is only active against L. infantum. Both oil extracts showed low cytotoxicity towards murine macrophages. The characteristic ratios (IC80 Raw264.7 cells/IC50 L. infantum and IC80 Raw264.7 cells/IC50 L. major) were, respectively, 2.7 and 1.57 for T. hirtus sp. algeriensis, and 1.34 and 0.19 for R. chalepensis. However, when measuring the antioxidant effects (DDPH method), the two latter EOs presented a moderate 2,2-diphenyl-2-picrylhydrazyl hydrate scavenging effects compared to EOs from Eucaliptus globulus, Pinus halepensis, Pituranthos tortuosus, Rosmarinus officinalis, Tetraclinis articulata or to BHT.
C1 [Ahmed, S. Ben Hadj; Guesmi, F.] Fac Sci Gafsa, Dept Biol, Gafsa, Tunisia.
[Sghaier, R. M.; Attia, H.; Laouini, D.] Inst Pasteur Tunis, Tunis 1002, Tunisia.
[Sghaier, R. M.; Attia, H.; Laouini, D.] NIAID, TMRC, NIH, Bethesda, MD USA.
[Sghaier, R. M.; Attia, H.; Laouini, D.] CNRS France, Lab Int Associe Ingn Biomol, Paris, France.
[Sghaier, R. M.; Attia, H.; Laouini, D.] WHO Collaborating Ctr Leishmaniais, Lab Immunopathol Vaccinol & Genet Mol, Madrid, Spain.
[Guesmi, F.] INSAT, Unite Genie Biol, Tunis 1080, Tunisia.
[Kaabi, B.] Inst Pasteur Tunis, Lab Epidemiol & Ecol Parasites, Tunis 1002, Tunisia.
[Mejri, M.] Inst Super Etud Technol Zaghouan, Mograne 1121, Tunisia.
RP Ahmed, SB (reprint author), Fac Sci Gafsa, Dept Biol, Campus Univ Zarroug Gafsa 2112, Gafsa, Tunisia.
EM s_benhadj@yahoo.fr; issam.smaali@insat.rnu.tn
RI Ahmed, Sofia/J-7876-2015
FU Ministere de l'Enseignement Superieur, de la Recherche Scientifique et
de la Technologie (Tunisia); TMRC NIAID/NIH [15P50A1074178]
FX This study was supported by a grant from the Ministere de l'Enseignement
Superieur, de la Recherche Scientifique et de la Technologie (Tunisia).
RMS and DL were partly supported by a TMRC NIAID/NIH grant (Grant
#15P50A1074178). We thank Mr Hamdi Lazhar, Engineer and Director of
Bouhedma Natural Park for the identification of the harvested plants
used in this study, Dr Chokri Messaoud (INSAT) for his help in the GC-MS
analyses and Dr Ghrabi-Gammar Zeineb for the management of specimens,
their identification and their deposit in the herbarium of the
Laboratory of Medicinal Plants (INAT).
NR 32
TC 18
Z9 19
U1 1
U2 14
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1478-6419
J9 NAT PROD RES
JI Nat. Prod. Res.
PY 2011
VL 25
IS 12
BP 1195
EP 1201
DI 10.1080/14786419.2010.534097
PG 7
WC Chemistry, Applied; Chemistry, Medicinal
SC Chemistry; Pharmacology & Pharmacy
GA 884EM
UT WOS:000299687700010
PM 21740286
ER
PT J
AU Wagner, W
Brenowitz, SD
Hammer, JA
AF Wagner, Wolfgang
Brenowitz, Stephan D.
Hammer, John A., III
TI Myosin-Va transports the endoplasmic reticulum into the dendritic spines
of Purkinje neurons
SO NATURE CELL BIOLOGY
LA English
DT Article
ID INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; HOMER FAMILY PROTEINS; MELANOSOME
TRANSPORT; HIPPOCAMPAL-NEURONS; GLUTAMATE-RECEPTOR; CALCIUM-RELEASE;
CEREBELLAR LTD; DILUTE LOCUS; NECK LENGTH; LEVER ARM
AB Extension of the endoplasmic reticulum (ER) into dendritic spines of Purkinje neurons is required for cerebellar synaptic plasticity and is disrupted in animals with null mutations in Myo5a, the gene encoding myosin-Va. We show here that myosin-Va acts as a point-to-point organelle transporter to pull ER as cargo into Purkinje neuron spines. Specifically, myosin-Va accumulates at the ER tip as the organelle moves into spines, and hydrolysis of ATP by myosin-Va is required for spine ER targeting. Moreover, myosin-Va is responsible for almost all of the spine ER insertion events. Finally, attenuation of the ability of myosin-Va to move along actin filaments reduces the maximum velocity of ER movement into spines, providing direct evidence that myosin-Va drives ER motility. Thus, we have established that an actin-based motor moves ER within animal cells, and have uncovered the mechanism for ER localization to Purkinje neuron spines, a prerequisite for synaptic plasticity.
C1 [Wagner, Wolfgang; Hammer, John A., III] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Brenowitz, Stephan D.] Natl Inst Deafness & Other Commun Disorders, Sect Synapt Transmiss, NIH, Bethesda, MD 20892 USA.
RP Hammer, JA (reprint author), NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
EM hammerj@nhlbi.nih.gov
FU Intramural NIH HHS [Z01 DC000072-01]
NR 63
TC 77
Z9 78
U1 1
U2 17
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1465-7392
J9 NAT CELL BIOL
JI Nat. Cell Biol.
PD JAN
PY 2011
VL 13
IS 1
BP 40
EP U101
DI 10.1038/ncb2132
PG 19
WC Cell Biology
SC Cell Biology
GA 697GV
UT WOS:000285502200009
PM 21151132
ER
PT J
AU Purdue, MP
Johansson, M
Zelenika, D
Toro, JR
Scelo, G
Moore, LE
Prokhortchouk, E
Wu, XF
Kiemeney, LA
Gaborieau, V
Jacobs, KB
Chow, WH
Zaridze, D
Matveev, V
Lubinski, J
Trubicka, J
Szeszenia-Dabrowska, N
Lissowska, J
Rudnai, P
Fabianova, E
Bucur, A
Bencko, V
Foretova, L
Janout, V
Boffetta, P
Colt, JS
Davis, FG
Schwartz, KL
Banks, RE
Selby, PJ
Harnden, P
Berg, CD
Hsing, AW
Grubb, RL
Boeing, H
Vineis, P
Clavel-Chapelon, F
Palli, D
Tumino, R
Krogh, V
Panico, S
Duell, EJ
Quiros, JR
Sanchez, MJ
Navarro, C
Ardanaz, E
Dorronsoro, M
Khaw, KT
Allen, NE
Bueno-De-Mesquita, HB
Peeters, PHM
Trichopoulos, D
Linseisen, J
Ljungberg, B
Overvad, K
Tjonneland, A
Romieu, I
Riboli, E
Mukeria, A
Shangina, O
Stevens, VL
Thun, MJ
Diver, WR
Gapstur, SM
Pharoah, PD
Easton, DF
Albanes, D
Weinstein, SJ
Virtamo, J
Vatten, L
Hveem, K
Njolstad, I
Tell, GS
Stoltenberg, C
Kumar, R
Koppova, K
Cussenot, O
Benhamou, S
Oosterwijk, E
Vermeulen, SH
Aben, KKH
van der Marel, SL
Ye, YQ
Wood, CG
Pu, X
Mazur, AM
Boulygina, ES
Chekanov, NN
Foglio, M
Lechner, D
Gut, I
Heath, S
Blanche, H
Hutchinson, A
Thomas, G
Wang, ZM
Yeager, M
Fraumeni, JF
Skryabin, KG
McKay, JD
Rothman, N
Chanock, SJ
Lathrop, M
Brennan, P
AF Purdue, Mark P.
Johansson, Mattias
Zelenika, Diana
Toro, Jorge R.
Scelo, Ghislaine
Moore, Lee E.
Prokhortchouk, Egor
Wu, Xifeng
Kiemeney, Lambertus A.
Gaborieau, Valerie
Jacobs, Kevin B.
Chow, Wong-Ho
Zaridze, David
Matveev, Vsevolod
Lubinski, Jan
Trubicka, Joanna
Szeszenia-Dabrowska, Neonila
Lissowska, Jolanta
Rudnai, Peter
Fabianova, Eleonora
Bucur, Alexandru
Bencko, Vladimir
Foretova, Lenka
Janout, Vladimir
Boffetta, Paolo
Colt, Joanne S.
Davis, Faith G.
Schwartz, Kendra L.
Banks, Rosamonde E.
Selby, Peter J.
Harnden, Patricia
Berg, Christine D.
Hsing, Ann W.
Grubb, Robert L., III
Boeing, Heiner
Vineis, Paolo
Clavel-Chapelon, Francoise
Palli, Domenico
Tumino, Rosario
Krogh, Vittorio
Panico, Salvatore
Duell, Eric J.
Quiros, Jose Ramon
Sanchez, Maria-Jose
Navarro, Carmen
Ardanaz, Eva
Dorronsoro, Miren
Khaw, Kay-Tee
Allen, Naomi E.
Bueno-de-Mesquita, H. Bas
Peeters, Petra H. M.
Trichopoulos, Dimitrios
Linseisen, Jakob
Ljungberg, Borje
Overvad, Kim
Tjonneland, Anne
Romieu, Isabelle
Riboli, Elio
Mukeria, Anush
Shangina, Oxana
Stevens, Victoria L.
Thun, Michael J.
Diver, W. Ryan
Gapstur, Susan M.
Pharoah, Paul D.
Easton, Douglas F.
Albanes, Demetrius
Weinstein, Stephanie J.
Virtamo, Jarmo
Vatten, Lars
Hveem, Kristian
Njolstad, Inger
Tell, Grethe S.
Stoltenberg, Camilla
Kumar, Rajiv
Koppova, Kvetoslava
Cussenot, Olivier
Benhamou, Simone
Oosterwijk, Egbert
Vermeulen, Sita H.
Aben, Katja K. H.
van der Marel, Saskia L.
Ye, Yuanqing
Wood, Christopher G.
Pu, Xia
Mazur, Alexander M.
Boulygina, Eugenia S.
Chekanov, Nikolai N.
Foglio, Mario
Lechner, Doris
Gut, Ivo
Heath, Simon
Blanche, Helene
Hutchinson, Amy
Thomas, Gilles
Wang, Zhaoming
Yeager, Meredith
Fraumeni, Joseph F., Jr.
Skryabin, Konstantin G.
McKay, James D.
Rothman, Nathaniel
Chanock, Stephen J.
Lathrop, Mark
Brennan, Paul
TI Genome-wide association study of renal cell carcinoma identifies two
susceptibility loci on 2p21 and 11q13.3
SO NATURE GENETICS
LA English
DT Article
ID DENSITY-LIPOPROTEIN HDL; KIDNEY CANCER; PROSTATE-CANCER; FAMILY-HISTORY;
PANCREATIC-CANCER; BREAST-CANCER; RISK; TRANSCRIPTION; EPIDEMIOLOGY;
CHOLESTEROL
AB We conducted a two-stage genome-wide association study of renal cell carcinoma (RCC) in 3,772 affected individuals (cases) and 8,505 controls of European background from 11 studies and followed up 6 SNPs in 3 replication studies of 2,198 cases and 4,918 controls. Two loci on the regions of 2p21 and 11q13.3 were associated with RCC susceptibility below genome-wide significance. Two correlated variants (r(2) = 0.99 in controls), rs11894252 (P = 1.8 x 10(-8)) and rs7579899 (P = 2.3 x 10(-9)), map to EPAS1 on 2p21, which encodes hypoxia-inducible-factor-2 alpha, a transcription factor previously implicated in RCC. The second locus, rs7105934, at 11q13.3, contains no characterized genes (P = 7.8 x 10(-14)). In addition, we observed a promising association on 12q24.31 for rs4765623, which maps to SCARB1, the scavenger receptor class B, member 1 gene (P = 2.6 x 10(-8)). Our study reports previously unidentified genomic regions associated with RCC risk that may lead to new etiological insights.
C1 [Purdue, Mark P.; Toro, Jorge R.; Moore, Lee E.; Jacobs, Kevin B.; Chow, Wong-Ho; Colt, Joanne S.; Hsing, Ann W.; Albanes, Demetrius; Weinstein, Stephanie J.; Hutchinson, Amy; Thomas, Gilles; Wang, Zhaoming; Yeager, Meredith; Fraumeni, Joseph F., Jr.; Rothman, Nathaniel; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA.
[Johansson, Mattias; Scelo, Ghislaine; Gaborieau, Valerie; Romieu, Isabelle; McKay, James D.; Brennan, Paul] Int Agcy Res Canc, F-69372 Lyon, France.
[Zelenika, Diana; Foglio, Mario; Lechner, Doris; Gut, Ivo; Heath, Simon; Lathrop, Mark] Ctr Natl Genotypage, Inst Genom, CEA, Evry, France.
[Prokhortchouk, Egor; Mazur, Alexander M.; Chekanov, Nikolai N.; Skryabin, Konstantin G.] Russian Acad Sci, Ctr Bioengn, Moscow, Russia.
[Prokhortchouk, Egor; Mazur, Alexander M.; Boulygina, Eugenia S.; Skryabin, Konstantin G.] Kurchatov Sci Ctr, Moscow, Russia.
[Wu, Xifeng; Ye, Yuanqing; Pu, Xia] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Div Canc Prevent & Populat Sci, Houston, TX 77030 USA.
[Kiemeney, Lambertus A.; Vermeulen, Sita H.; Aben, Katja K. H.] Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol Biostat & Hlth Technol Assessment, NL-6525 ED Nijmegen, Netherlands.
[Kiemeney, Lambertus A.; Oosterwijk, Egbert] Radboud Univ Nijmegen, Med Ctr, Dept Urol, NL-6525 ED Nijmegen, Netherlands.
[Jacobs, Kevin B.; Hutchinson, Amy; Thomas, Gilles; Wang, Zhaoming; Yeager, Meredith] NCI, Core Genotyping Facil, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Zaridze, David; Matveev, Vsevolod; Mukeria, Anush; Shangina, Oxana] Russian NN Blokhin Canc Res Ctr, Moscow, Russia.
[Lubinski, Jan; Trubicka, Joanna] Pomeranian Med Univ, Dept Genet & Pathomorphol, Int Hereditary Canc Ctr, Szczecin, Poland.
[Szeszenia-Dabrowska, Neonila] Inst Occupat Med, Dept Epidemiol, Lodz, Poland.
[Lissowska, Jolanta] Maria Sklodowska Curie Mem Canc Ctr, Warsaw, Poland.
[Lissowska, Jolanta] Inst Oncol, Warsaw, Poland.
[Rudnai, Peter] Natl Inst Environm Hlth, Dept Environm Epidemiol, Budapest, Hungary.
[Fabianova, Eleonora] Reg Author Publ Hlth, Banska Bystrica, Slovakia.
[Bucur, Alexandru] Inst Publ Hlth, Bucharest, Romania.
[Bencko, Vladimir] Charles Univ Prague, Fac Med 1, Inst Hyg & Epidemiol, Prague, Czech Republic.
[Foretova, Lenka] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic.
[Janout, Vladimir] Palacky Univ, CR-77147 Olomouc, Czech Republic.
[Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA.
[Davis, Faith G.] Univ Illinois, Sch Publ Hlth, Div Epidemiol & Biostat, Chicago, IL USA.
[Schwartz, Kendra L.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA.
[Schwartz, Kendra L.] Wayne State Univ, Dept Family Med, Detroit, MI USA.
[Banks, Rosamonde E.; Selby, Peter J.] St James Univ Hosp, Leeds Inst Mol Med, Canc Res UK Ctr, Leeds, W Yorkshire, England.
[Harnden, Patricia] St James Univ Hosp, Dept Pathol, Leeds, W Yorkshire, England.
[Berg, Christine D.] NCI, Canc Prevent Div, NIH, US Dept HHS, Bethesda, MD 20892 USA.
[Grubb, Robert L., III] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA.
[Boeing, Heiner] German Inst Human Nutr, Dept Epidemiol, Potsdam, Nuthetal, Germany.
[Vineis, Paolo; Peeters, Petra H. M.; Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, London, England.
[Vineis, Paolo] Univ London Imperial Coll Sci Technol & Med, Ctr Environm & Hlth, MRC HPA, London, England.
[Vineis, Paolo] Human Genet Fdn HuGeF, Turin, Italy.
[Clavel-Chapelon, Francoise] Inst Gustave Roussy, Ctr Res Epidemiol & Populat Hlth, INSERM, Villejuif, France.
[Clavel-Chapelon, Francoise] Paris S Univ, UMRS 1018, Villejuif, France.
[Palli, Domenico] Canc Res & Prevent Inst ISPO, Mol & Nutr Epidemiol Unit, Florence, Italy.
[Tumino, Rosario] Azienda Osped Civile MP Arezzo, Canc Registry, Ragusa, Italy.
[Krogh, Vittorio] Ist Nazl Tumori, Fdn Ist Ricovero & Cura Carattere Sci IRCCS, Nutr Epidemiol Unit, I-20133 Milan, Italy.
[Panico, Salvatore] Univ Naples Federico 2, Dept Clin & Expt Med, Naples, Italy.
[Duell, Eric J.] Catalan Inst Oncol ICO IDIBELL, Canc Epidemiol Res Program, Unit Nutr Environm & Canc, Barcelona, Spain.
[Quiros, Jose Ramon] Consejeria Serv Sociales, Jefe Secc Informac Sanitaria, Oviedo, Spain.
[Sanchez, Maria-Jose] Andalusian Sch Publ Hlth, Granada, Spain.
[Sanchez, Maria-Jose; Navarro, Carmen; Ardanaz, Eva; Dorronsoro, Miren] CIBER Epidemiol & Salud Publ CIBERESP, Barcelona, Spain.
[Navarro, Carmen] Reg Council Hlth & Consumer Affairs, Dept Epidemiol, Murcia, Spain.
[Ardanaz, Eva] Publ Hlth Inst Navarra, Pamplona, Spain.
[Dorronsoro, Miren] Basque Reg Hlth Dept, Publ Hlth Div Gipuzkoa, San Sebastian, Spain.
[Khaw, Kay-Tee] Univ Cambridge, Dept Publ Hlth & Primary Care, Dept Gerontol, Cambridge, England.
[Allen, Naomi E.] Univ Oxford, Nuffield Dept Clin Med, Canc Epidemiol Unit, Oxford, England.
[Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands.
[Peeters, Petra H. M.] Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
[Trichopoulos, Dimitrios] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Trichopoulos, Dimitrios] Acad Athens, Bur Epidemiol Res, Athens, Greece.
[Linseisen, Jakob] German Canc Res Ctr, Div Canc Epidemiol, D-6900 Heidelberg, Germany.
[Linseisen, Jakob] Helmholtz Ctr Munich, Inst Epidemiol, Munich, Germany.
[Ljungberg, Borje] Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden.
[Overvad, Kim; Stevens, Victoria L.; Diver, W. Ryan] Aarhus Univ, Sch Publ Hlth, Dept Epidemiol, Aarhus, Denmark.
[Tjonneland, Anne] Inst Canc Epidemiol, Danish Canc Soc, Copenhagen, Denmark.
[Thun, Michael J.; Gapstur, Susan M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Pharoah, Paul D.; Easton, Douglas F.] Univ Cambridge, Dept Oncol, Cambridge, England.
[Pharoah, Paul D.; Easton, Douglas F.] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
[Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
[Vatten, Lars; Hveem, Kristian] Norwegian Univ Sci & Technol, Fac Med, Dept Publ Hlth, N-7034 Trondheim, Norway.
[Njolstad, Inger] Univ Tromso, Dept Community Med, Tromso, Norway.
[Tell, Grethe S.] Univ Bergen, Dept Publ Hlth & Primary Hlth Care, Bergen, Norway.
[Stoltenberg, Camilla] Norwegian Inst Publ Hlth, Div Epidemiol, Oslo, Norway.
[Kumar, Rajiv] German Canc Res Ctr, Div Mol Genet Epidemiol, D-6900 Heidelberg, Germany.
[Koppova, Kvetoslava] Reg Author Publ Hlth, Dept Environm Hyg, Banska Bystrica, Slovakia.
[Cussenot, Olivier] Univ Paris 06, Tenon Hosp, APHP, CeRePP,ER2, Paris, France.
[Benhamou, Simone] Fdn Jean Dausset, Ctr Etud Polymorphisme Humain, INSERM, U946, Paris, France.
[Benhamou, Simone] Inst Gustave Roussy, CNRS, UMR8200, Villejuif, France.
[Vermeulen, Sita H.; van der Marel, Saskia L.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands.
[Aben, Katja K. H.] Comprehens Canc Ctr E, Dept Canc Registry & Res, Nijmegen, Netherlands.
[Wood, Christopher G.] Univ Texas MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA.
RP Chanock, SJ (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA.
EM chanocks@mail.nih.gov; brennan@iarc.fr
RI Tell, Grethe/G-5639-2015; Purdue, Mark/C-9228-2016; Vermeulen,
H.H.M./L-4716-2015; Aben, Katja/G-9686-2016; Prokhortchouk,
Egor/I-9108-2014; Benhamou, Simone/K-6554-2015; Krogh,
Vittorio/K-2628-2016; Panico, Salvatore/K-6506-2016; Kiemeney,
Lambertus/D-3357-2009; Clavel-Chapelon, Francoise/G-6733-2014; Berg ,
Christine/K-1047-2014; Janout, Vladimir/M-5133-2014; Oosterwijk,
Egbert/P-5466-2014; SANCHEZ-PEREZ, MARIA JOSE/D-1087-2011;
Szeszenia-Dabrowska, Neonila/F-7190-2010; Pu, Xia/H-2670-2012; Heath,
Simon/J-4138-2012; Zaridze, David/K-5605-2013; Linseisen,
Jakob/B-5353-2014; Albanes, Demetrius/B-9749-2015;
OI Tell, Grethe/0000-0003-1386-1638; Purdue, Mark/0000-0003-1177-3108;
Aben, Katja/0000-0002-0214-2147; Krogh, Vittorio/0000-0003-0122-8624;
Panico, Salvatore/0000-0002-5498-8312; Chekanov,
Nikolay/0000-0003-1131-3195; Kumar, Rajiv/0000-0002-6093-0395; Duell,
Eric J/0000-0001-5256-0163; Kiemeney, Lambertus/0000-0002-2368-1326;
SANCHEZ-PEREZ, MARIA JOSE/0000-0003-4817-0757; Linseisen,
Jakob/0000-0002-9386-382X; Lissowska, Jolanta/0000-0003-2695-5799;
Banks, Rosamonde/0000-0002-0042-8715; PALLI,
Domenico/0000-0002-5558-2437
FU French Institut National du Cancer (INCa); National Cancer Institute
(NCI), US National Institutes of Health (NIH)
FX The authors thank all of the participants who took part in this research
and the funders and support staff who made this study possible. Funding
for the genome-wide genotyping was provided by the French Institut
National du Cancer (INCa) for those studies coordinated by IARC/CNG, and
by the intramural research program of the National Cancer Institute
(NCI), US National Institutes of Health (NIH) for those studies
coordinated by the NCI. Additional acknowledgments can be found in the
Supplementary Note.
NR 37
TC 112
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U1 3
U2 32
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD JAN
PY 2011
VL 43
IS 1
BP 60
EP U83
DI 10.1038/ng.723
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 699SQ
UT WOS:000285683500017
PM 21131975
ER
PT J
AU Yamane, A
Resch, W
Kuo, N
Kuchen, S
Li, ZY
Sun, HW
Robbiani, DF
McBride, K
Nussenzweig, MC
Casellas, R
AF Yamane, Arito
Resch, Wolfgang
Kuo, Nan
Kuchen, Stefan
Li, Zhiyu
Sun, Hong-wei
Robbiani, Davide F.
McBride, Kevin
Nussenzweig, Michel C.
Casellas, Rafael
TI Deep-sequencing identification of the genomic targets of the cytidine
deaminase AID and its cofactor RPA in B lymphocytes
SO NATURE IMMUNOLOGY
LA English
DT Article
ID CLASS-SWITCH RECOMBINATION; RNA-POLYMERASE-II; ACTIVATION-INDUCED
DEAMINASE; REPLICATION PROTEIN-A; SOMATIC HYPERMUTATION; C-MYC;
IMMUNOGLOBULIN GENES; CELL LYMPHOMAS; KINASE-A; IG GENES
AB The cytidine deaminase AID hypermutates immunoglobulin genes but can also target oncogenes, leading to tumorigenesis. The extent of AID's promiscuity and its predilection for immunoglobulin genes are unknown. We report here that AID interacted broadly with promoter-proximal sequences associated with stalled polymerases and chromatin-activating marks. In contrast, genomic occupancy of replication protein A (RPA), an AID cofactor, was restricted to immunoglobulin genes. The recruitment of RPA to the immunoglobulin loci was facilitated by phosphorylation of AID at Ser38 and Thr140. We propose that stalled polymerases recruit AID, thereby resulting in low frequencies of hypermutation across the B cell genome. Efficient hypermutation and switch recombination required AID phosphorylation and correlated with recruitment of RPA. Our findings provide a rationale for the oncogenic role of AID in B cell malignancy.
C1 [Robbiani, Davide F.; McBride, Kevin; Nussenzweig, Michel C.] Rockefeller Univ, Howard Hughes Med Inst, Lab Mol Immunol, New York, NY 10021 USA.
[Yamane, Arito; Resch, Wolfgang; Kuo, Nan; Kuchen, Stefan; Li, Zhiyu; Sun, Hong-wei; Casellas, Rafael] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Casellas, Rafael] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Nussenzweig, MC (reprint author), Rockefeller Univ, Howard Hughes Med Inst, Lab Mol Immunol, New York, NY 10021 USA.
EM nussen@mail.rockefeller.edu; casellar@mail.nih.gov
RI mcbride, kevin/E-8230-2011; Yamane, Arito/A-2959-2013;
OI Kuchen, Stefan/0000-0003-4899-8132
FU National Institutes of Health (National Institute of Arthritis and
Musculoskeletal and Skin Diseases) [AI037526]; Howard Hughes Medical
Institute
FX We thank D. Schatz for comments on the manuscript; J. Chaudhuri
(Memorial Sloan-Kettering Cancer Center) and F. Alt (Harvard University)
for antibodies to AID; J. Simone for cell sorting; G. Gutierrez for
technical assistance with the genome analyzer; and C. Ansarah-Sobrinho
and S. Nelson for help with sequencing. Supported by the National
Institutes of Health (Intramural Research Program of the National
Institute of Arthritis and Musculoskeletal and Skin Diseases; and
AI037526 to M.C.N.) and the Howard Hughes Medical Institute (M.C.N.).
NR 50
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U1 0
U2 8
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 JAN
PY 2011
VL 12
IS 1
BP 62
EP U85
DI 10.1038/ni.1964
PG 9
WC Immunology
SC Immunology
GA 696TU
UT WOS:000285465100014
PM 21113164
ER
PT J
AU Maul, RW
Saribasak, H
Martomo, SA
McClure, RL
Yang, W
Vaisman, A
Gramlich, HS
Schatz, DG
Woodgate, R
Wilson, DM
Gearhart, PJ
AF Maul, Robert W.
Saribasak, Huseyin
Martomo, Stella A.
McClure, Rhonda L.
Yang, William
Vaisman, Alexandra
Gramlich, Hillary S.
Schatz, David G.
Woodgate, Roger
Wilson, David M., III
Gearhart, Patricia J.
TI Uracil residues dependent on the deaminase AID in immunoglobulin gene
variable and switch regions
SO NATURE IMMUNOLOGY
LA English
DT Article
ID INDUCED CYTIDINE DEAMINASE; SINGLE-STRANDED-DNA; LIGHT-CHAIN GENE;
SOMATIC HYPERMUTATION; B-CELLS; ANTIBODY DIVERSIFICATION; GLYCOSYLASE
ACTIVITY; R-LOOPS; RECOMBINATION; MICE
AB Activation-induced deaminase (AID) initiates diversity of immunoglobulin genes through deamination of cytosine to uracil. Two opposing models have been proposed for the deamination of DNA or RNA by AID. Although most data support DNA deamination, there is no physical evidence of uracil residues in immunoglobulin genes. Here we demonstrate their presence by determining the sensitivity of DNA to digestion with uracil DNA glycosylase (UNG) and abasic endonuclease. Using several methods of detection, we identified uracil residues in the variable and switch regions. Uracil residues were generated within 24 h of B cell stimulation, were present on both DNA strands and were found to replace mainly cytosine bases. Our data provide direct evidence for the model that AID functions by deaminating cytosine residues in DNA.
C1 [Maul, Robert W.; Saribasak, Huseyin; Martomo, Stella A.; McClure, Rhonda L.; Yang, William; Wilson, David M., III; Gearhart, Patricia J.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
[Vaisman, Alexandra; Woodgate, Roger] NICHHD, Lab Genom Integr, NIH, Bethesda, MD 20892 USA.
[Gramlich, Hillary S.] Yale Univ, Sch Med, Howard Hughes Med Inst, Dept Cell Biol, New Haven, CT 06510 USA.
[Schatz, David G.] Yale Univ, Sch Med, Howard Hughes Med Inst, Dept Immunol, New Haven, CT 06510 USA.
RP Gearhart, PJ (reprint author), NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
EM gearhartp@mail.nih.gov
RI Saribasak, Huseyin/C-9331-2012; Schatz, David/A-6748-2013; Vaisman,
Alexandra/C-3766-2013;
OI Saribasak, Huseyin/0000-0003-0055-062X; Schatz,
David/0000-0002-5669-1176; Vaisman, Alexandra/0000-0002-2521-1467; Maul,
Robert/0000-0002-6958-8514
FU Howard Hughes Medical Institute; National Institute on Aging; National
Institute of Child Health and Human Development of the National
Institutes of Health
FX We thank J. Stivers (John Hopkins University) for UNG; S. Wilson
(National Institute of Environmental Health Sciences, National
Institutes of Health) for polymerase beta-lyase; R. Kohli (University of
Pennsylvania), J. Buerstedde and H. Arakawa (Max Planck Institute of
Biochemistry) for reagents and advice; S. Fugmann and R. Sen for
discussions; T. Wolf, C. Nguyen and R. Wersto for assistance in flow
cytometry; and the Comparative Medicine Section for mouse maintenance.
Supported by the National Institute on Aging and the National Institute
of Child Health and Human Development of the National Institutes of
Health (Intramural Research Program) and Howard Hughes Medical Institute
(D.G.S.).
NR 55
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U1 2
U2 3
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 JAN
PY 2011
VL 12
IS 1
BP 70
EP U93
DI 10.1038/ni.1970
PG 8
WC Immunology
SC Immunology
GA 696TU
UT WOS:000285465100015
PM 21151102
ER
PT J
AU Maruyama, T
Li, J
Vaque, JP
Konkel, JE
Wang, WF
Zhang, BJ
Zhang, P
Zamarron, BF
Yu, DY
Wu, YT
Zhuang, YA
Gutkind, JS
Chen, WJ
AF Maruyama, Takashi
Li, Jun
Vaque, Jose P.
Konkel, Joanne E.
Wang, Weifeng
Zhang, Baojun
Zhang, Pin
Zamarron, Brian F.
Yu, Dongyang
Wu, Yuntao
Zhuang, Yuan
Gutkind, J. Silvio
Chen, WanJun
TI Control of the differentiation of regulatory T cells and T(H)17 cells by
the DNA-binding inhibitor Id3
SO NATURE IMMUNOLOGY
LA English
DT Article
ID TRANSCRIPTION FACTOR FOXP3; ROR-GAMMA-T; GROWTH-FACTOR-BETA; TGF-BETA;
CD3-SPECIFIC ANTIBODY; GENE-EXPRESSION; TOLERANCE; PROTEINS; RECEPTOR;
LINEAGE
AB The molecular mechanisms that direct transcription of the gene encoding the transcription factor Foxp3 in CD4(+) T cells remain ill-defined. We show here that deletion of the DNA-binding inhibitor Id3 resulted in the defective generation of Foxp3(+) regulatory T cells (T-reg cells). We identify two transforming growth factor-beta 1 (TGF-beta 1)-dependent mechanisms that were vital for activation of Foxp3 transcription and were defective in Id3(-/-) CD4(+) T cells. Enhanced binding of the transcription factor E2A to the Foxp3 promoter promoted Foxp3 transcription. Id3 was required for relief of inhibition by the transcription factor GATA-3 at the Foxp3 promoter. Furthermore, Id3(-/-) T cells showed greater differentiation into the T(H)17 subset of helper T cells in vitro and in a mouse asthma model. Therefore, a network of factors acts in a TGF-beta-dependent manner to control Foxp3 expression and inhibit the development of T(H)17 cells.
C1 [Maruyama, Takashi; Li, Jun; Konkel, Joanne E.; Zhang, Pin; Zamarron, Brian F.; Chen, WanJun] Natl Inst Dent & Craniofacial Res, Mucosal Immunol Unit, Oral Infect & Immun Branch, NIH, Bethesda, MD USA.
[Vaque, Jose P.; Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Oral Pharyngeal Canc Branch, NIH, Bethesda, MD USA.
[Wang, Weifeng; Yu, Dongyang; Wu, Yuntao] George Mason Univ, Dept Microbiol & Mol Biol, Manassas, VA USA.
[Zhang, Baojun; Zhuang, Yuan] Duke Univ, Dept Immunol, Durham, NC 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
RI Gutkind, J. Silvio/A-1053-2009; wang, weifeng/N-4140-2013; ZHANG,
BAOJUN/N-3863-2014; MaruYama, Takashi/N-5994-2014; Li, Jun/N-6267-2015;
Vaque, Jose/H-8413-2015;
OI ZHANG, BAOJUN/0000-0002-7786-4304; Vaque, Jose/0000-0002-3913-2495;
Zamarron, Brian/0000-0001-6549-4230
FU National Institute of Dental and Craniofacial Research (US National
Institutes of Health)
FX We thank Y.H. Chen, Q. Ruan and M. Tone (University of Pennsylvania) for
Foxp3 constructs and EL4 LAF cells. Supported by the Intramural Research
Program of the National Institute of Dental and Craniofacial Research
(US National Institutes of Health).
NR 49
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U1 2
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 JAN
PY 2011
VL 12
IS 1
BP 86
EP U114
DI 10.1038/ni.1965
PG 11
WC Immunology
SC Immunology
GA 696TU
UT WOS:000285465100017
PM 21131965
ER
PT J
AU Vaegter, CB
Jansen, P
Fjorback, AW
Glerup, S
Skeldal, S
Kjolby, M
Richner, M
Erdmann, B
Nyengaard, JR
Tessarollo, L
Lewin, GR
Willnow, TE
Chao, MV
Nykjaer, A
AF Vaegter, Christian B.
Jansen, Pernille
Fjorback, Anja W.
Glerup, Simon
Skeldal, Sune
Kjolby, Mads
Richner, Mette
Erdmann, Bettina
Nyengaard, Jens R.
Tessarollo, Lino
Lewin, Gary R.
Willnow, Thomas E.
Chao, Moses V.
Nykjaer, Anders
TI Sortilin associates with Trk receptors to enhance anterograde transport
and neurotrophin signaling
SO NATURE NEUROSCIENCE
LA English
DT Article
ID DORSAL-ROOT GANGLION; SENSORY NEURONS; NERVOUS-SYSTEM;
BIOCHEMICAL-CHARACTERIZATION; TARGETED DISRUPTION; AXONAL-TRANSPORT;
MICE LACKING; GENE; PROTEIN; BRAIN
AB Binding of target-derived neurotrophins to Trk receptors at nerve terminals is required to stimulate neuronal survival, differentiation, innervation and synaptic plasticity. The distance between the soma and nerve terminal is great, making efficient anterograde Trk transport critical for Trk synaptic translocation and signaling. The mechanism responsible for this trafficking remains poorly understood. Here we show that the sorting receptor sortilin interacts with TrkA, TrkB and TrkC and enables their anterograde axonal transport, thereby enhancing neurotrophin signaling. Cultured DRG neurons lacking sortilin showed blunted MAP kinase signaling and reduced neurite outgrowth upon stimulation with NGF. Moreover, deficiency for sortilin markedly aggravated TrkA, TrkB and TrkC phenotypes present in p75(NTR) knockouts, and resulted in increased embryonic lethality and sympathetic neuropathy in mice heterozygous for TrkA. Our findings demonstrate a role for sortilin as an anterograde trafficking receptor for Trk and a positive modulator of neurotrophin-induced neuronal survival.
C1 [Vaegter, Christian B.; Jansen, Pernille; Glerup, Simon; Skeldal, Sune; Kjolby, Mads; Richner, Mette; Nykjaer, Anders] Aarhus Univ, Dept Med Biochem, Lundbeck Fdn, Res Ctr MIND, Aarhus, Denmark.
[Fjorback, Anja W.; Nyengaard, Jens R.] Aarhus Univ, Stereol & Electron Microscopy Lab, Lundbeck Fdn, Res Ctr MIND, Aarhus, Denmark.
[Erdmann, Bettina; Lewin, Gary R.; Willnow, Thomas E.] Max Delbruck Ctr Mol Med, Berlin, Germany.
[Tessarollo, Lino] NCI, Ctr Canc Res, Frederick, MD 21701 USA.
[Chao, Moses V.] NYU, Sch Med, Skirball Inst Biomol Med, Kimmel Ctr, New York, NY USA.
RP Nykjaer, A (reprint author), Aarhus Univ, Dept Med Biochem, Lundbeck Fdn, Res Ctr MIND, Aarhus, Denmark.
EM cv@biokemi.au.dk; an@biokemi.au.dk
RI Vaegter, Christian/A-7909-2008; Kjolby, Mads/F-3672-2011;
OI Vaegter, Christian/0000-0001-6573-146X; Nykjaer,
Anders/0000-0001-6422-6736; Kjolby, Mads/0000-0002-1043-6137; Chao,
Moses/0000-0002-6969-3744; Lewin, Gary/0000-0002-2890-6352
FU Lundbeck Foundation; Danish Medical Research Council; Elvira and Rasmus
Rissforts Foundation; MEMORIES (European Union); US National Institutes
of Health [NS21072, AG025970, HD23315]; Deutsche Forschungsgemeinschaft;
Danish Council for Strategic Research; Center for Stochastic Geometry
and Advanced Bioimaging (Villum Foundation)
FX We thank L. Reichardt (University of California, San Francisco) for the
TrkA antibody. The ImageJ KymoToolBox plug-in was kindly provided by F.
Cordelieres (Universite Paris-Sud Orsay), and the NeuriteTracer plug-in
by M. Pool (Rue University). This work was supported by the Lundbeck
Foundation, The Danish Medical Research Council, Elvira and Rasmus
Rissforts Foundation, MEMORIES (European Union, Framework Programme 6),
US National Institutes of Health (NS21072, AG025970 and HD23315), the
Deutsche Forschungsgemeinschaft, Danish Council for Strategic Research,
and Center for Stochastic Geometry and Advanced Bioimaging (Villum
Foundation).
NR 50
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U1 4
U2 15
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD JAN
PY 2011
VL 14
IS 1
BP 54
EP U78
DI 10.1038/nn.2689
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 699TE
UT WOS:000285684900014
PM 21102451
ER
PT J
AU Noskov, VN
Chuang, RY
Gibson, DG
Leem, SH
Larionov, V
Kouprina, N
AF Noskov, Vladimir N.
Chuang, Ray-Yuan
Gibson, Daniel G.
Leem, Sun-Hee
Larionov, Vladimir
Kouprina, Natalay
TI Isolation of circular yeast artificial chromosomes for synthetic biology
and functional genomics studies
SO NATURE PROTOCOLS
LA English
DT Article
ID TRANSFORMATION-ASSOCIATED RECOMBINATION; MYCOPLASMA-GENITALIUM GENOME;
HUMAN DNA; CLONING; GENE; FRAGMENTS; VECTOR; EXPRESSION; CENTROMERE;
EVOLUTION
AB Circular yeast artificial chromosomes (YACs) provide significant advantages for cloning and manipulating large segments of genomic DNA in Saccharomyces cerevisiae. However, it has been difficult to exploit these advantages, because circular YACs are difficult to isolate and purify. Here we describe a method for purification of large circular YACs that is more reliable compared with previously described protocols. This method has been used to purify YACs up to 600 kb in size. The purified YAC DNA is suitable for restriction enzyme digestion, DNA sequencing and functional studies. For example, YACs carrying full-size genes can be purified from yeast and used for transfection into mammalian cells or for the construction of a synthetic genome that can be used to produce a synthetic cell. This method for isolating high-quality YAC DNA in microgram quantities should be valuable for functional and synthetic genomic studies. The entire protocol takes similar to 3 d to complete.
C1 [Leem, Sun-Hee; Larionov, Vladimir; Kouprina, Natalay] NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA.
[Noskov, Vladimir N.; Chuang, Ray-Yuan; Gibson, Daniel G.] J Craig Venter Inst, Rockville, MD USA.
[Leem, Sun-Hee] Dong A Univ, Dept Biol Sci, Pusan, South Korea.
RP Kouprina, N (reprint author), NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA.
EM kouprinn@mail.nih.gov
FU Synthetic Genomics (SGI); National Institutes of Health National Cancer
Institute, Center for Cancer Research
FX The research reported in this article was supported by Synthetic
Genomics (SGI) (V.N.N., R.-Y.C. and D.G.G.) and by the intramural
research program of the National Institutes of Health National Cancer
Institute, Center for Cancer Research (V.L. and N.K.).
NR 24
TC 11
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U1 2
U2 12
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1754-2189
J9 NAT PROTOC
JI Nat. Protoc.
PD JAN
PY 2011
VL 6
IS 1
BP 89
EP 96
DI 10.1038/nprot.2010.174
PG 8
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 703FY
UT WOS:000285965000009
PM 21212778
ER
PT J
AU Fleg, JL
Aronow, WS
Frishman, WH
AF Fleg, Jerome L.
Aronow, Wilbert S.
Frishman, William H.
TI Cardiovascular drug therapy in the elderly: benefits and challenges
SO NATURE REVIEWS CARDIOLOGY
LA English
DT Review
ID ACUTE CORONARY SYNDROMES; RANDOMIZED CONTROLLED-TRIAL;
CONGESTIVE-HEART-FAILURE; ISOLATED SYSTOLIC HYPERTENSION;
LEFT-VENTRICULAR DYSFUNCTION; CONVERTING-ENZYME INHIBITORS; ACUTE
MYOCARDIAL-INFARCTION; TYPE-2 DIABETES-MELLITUS; ST-SEGMENT-ELEVATION;
END-POINT REDUCTION
AB Increasing life expectancy in industrialized societies has resulted in a huge population of older adults with cardiovascular disease. Despite advances in device therapy and surgery, the mainstay of treatment for these disorders remains pharmacological. Hypertension affects two-thirds of older adults and remains a potent risk factor for coronary artery disease, chronic heart failure, atrial fibrillation, and stroke in this age group. Numerous trials have demonstrated reduction in these adverse outcomes with antihypertensive drugs. After acute myocardial infarction, beta-adrenergic blockers reduce mortality regardless of patient age. Statins and antiplatelet drugs have proven beneficial in both primary and, especially, secondary prevention of coronary events in older adults. In elders with chronic heart failure, loop diuretics must be used cautiously, owing to their higher potential for adverse effects, whereas angiotensin-converting-enzyme inhibitors and beta-blockers reduce symptoms and prolong survival. The high risk of stroke in elderly patients with atrial fibrillation is markedly reduced with warfarin, although bleeding risk is increased. The high prevalence of polypharmacy among older adults with cardiovascular disease, coupled with age-associated physiological changes and comorbidities, provides major challenges in adherence and avoidance of drug-related adverse events.
C1 [Fleg, Jerome L.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Aronow, Wilbert S.; Frishman, William H.] New York Med Coll, Dept Med, Valhalla, NY 10595 USA.
RP Fleg, JL (reprint author), NHLBI, Div Cardiovasc Sci, 6701 Rockledge Dr, Bethesda, MD 20892 USA.
EM flegj@nhlbi.nih.gov
NR 144
TC 44
Z9 45
U1 3
U2 14
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-5002
J9 NAT REV CARDIOL
JI Nat. Rev. Cardiol.
PD JAN
PY 2011
VL 8
IS 1
BP 13
EP 28
DI 10.1038/nrcardio.2010.162
PG 16
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 696PI
UT WOS:000285453400004
PM 20978470
ER
PT J
AU Saleh, M
Trinchieri, G
AF Saleh, Maya
Trinchieri, Giorgio
TI Innate immune mechanisms of colitis and colitis-associated colorectal
cancer
SO NATURE REVIEWS IMMUNOLOGY
LA English
DT Review
ID INFLAMMATORY-BOWEL-DISEASE; GENOME-WIDE ASSOCIATION; DEXTRAN
SODIUM-SULFATE; INTESTINAL EPITHELIAL-CELLS; DIET-INDUCED OBESITY; T-BET
DEFICIENCY; CROHNS-DISEASE; COLON CARCINOGENESIS; ULCERATIVE-COLITIS;
DENDRITIC CELLS
AB The innate immune system provides first-line defences in response to invading microorganisms and endogenous danger signals by triggering robust inflammatory and antimicrobial responses. However, innate immune sensing of commensal microorganisms in the intestinal tract does not lead to chronic intestinal inflammation in healthy individuals, reflecting the intricacy of the regulatory mechanisms that tame the inflammatory response in the gut. Recent findings suggest that innate immune responses to commensal microorganisms, although once considered to be harmful, are necessary for intestinal homeostasis and immune tolerance. This Review discusses recent findings that identify a crucial role for innate immune effector molecules in protection against colitis and colitis-associated colorectal cancer and the therapeutic implications that ensue.
C1 [Saleh, Maya] McGill Univ, Dept Med, Montreal, PQ H3G 0B1, Canada.
[Trinchieri, Giorgio] NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA.
RP Saleh, M (reprint author), McGill Univ, Dept Med, Montreal, PQ H3G 0B1, Canada.
EM maya.saleh@mcgill.ca; trinchig@mail.nih.gov
FU Canadian Institutes for Health Research [MOP-79410, MOP-82801,
MOP-86546, CTP-87520]; Burroughs Wellcome Fund; US National Institutes
of Health, National Cancer Institute, Center for Cancer Research, USA
FX M.S. thanks the students and colleagues in her laboratory for reading
and commenting on this manuscript. Work in M.S.'s laboratory is
supported by the Canadian Institutes for Health Research (MOP-79410,
MOP-82801, MOP-86546, CTP-87520) and the Burroughs Wellcome Fund. Work
in G.T.'s laboratory is supported by the Intramural Research Program of
the US National Institutes of Health, National Cancer Institute, Center
for Cancer Research, USA.
NR 130
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U1 8
U2 33
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-1733
J9 NAT REV IMMUNOL
JI Nat. Rev. Immunol.
PD JAN
PY 2011
VL 11
IS 1
BP 9
EP 20
DI 10.1038/nri2891
PG 12
WC Immunology
SC Immunology
GA 698DR
UT WOS:000285572600010
PM 21151034
ER
PT J
AU Balagopalan, L
Sherman, E
Barr, VA
Samelson, LE
AF Balagopalan, Lakshmi
Sherman, Eilon
Barr, Valarie A.
Samelson, Lawrence E.
TI Imaging techniques for assaying lymphocyte activation in action
SO NATURE REVIEWS IMMUNOLOGY
LA English
DT Review
ID T-CELL-RECEPTOR; RESONANCE ENERGY-TRANSFER; IMMUNOLOGICAL SYNAPSE
FORMATION; FC-EPSILON-RI; MICROTUBULE-ORGANIZING CENTER; PLASMA-MEMBRANE
MICRODOMAINS; NODE B-CELLS; ANTIGEN RECEPTOR; LIPID RAFTS; 2-PHOTON
MICROSCOPY
AB Imaging techniques have greatly improved our understanding of lymphocyte activation. Technical advances in spatial and temporal resolution and new labelling tools have enabled researchers to directly observe the activation process. Consequently, research using imaging approaches to study lymphocyte activation has expanded, providing an unprecedented level of cellular and molecular detail in the field. As a result, certain models of lymphocyte activation have been verified, others have been revised and yet others have been replaced with new concepts. In this article, we review the current imaging techniques that are used to assess lymphocyte activation in different contexts, from whole animals to single molecules, and discuss the advantages and potential limitations of these methods.
C1 [Balagopalan, Lakshmi; Sherman, Eilon; Barr, Valarie A.; Samelson, Lawrence E.] NCI, Lab Cellular & Mol Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Samelson, LE (reprint author), NCI, Lab Cellular & Mol Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM samelson@helix.nih.gov
RI Sherman, Eilon /B-3688-2014
OI Sherman, Eilon /0000-0002-7403-6036
FU National Institutes of Health (NIH), National Cancer Institute (NCI),
Center for Cancer Research (CCR)
FX We thank R. Kortum for critically reading the manuscript. This research
was supported by the Intramural Research Program of the National
Institutes of Health (NIH), National Cancer Institute (NCI), Center for
Cancer Research (CCR).
NR 129
TC 36
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U1 1
U2 17
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-1733
J9 NAT REV IMMUNOL
JI Nat. Rev. Immunol.
PD JAN
PY 2011
VL 11
IS 1
BP 21
EP 33
DI 10.1038/nri2903
PG 13
WC Immunology
SC Immunology
GA 698DR
UT WOS:000285572600011
PM 21179118
ER
PT J
AU Koup, RA
Graham, BS
Douek, DC
AF Koup, Richard A.
Graham, Barney S.
Douek, Daniel C.
TI The quest for a T cell-based immune correlate of protection against HIV:
a story of trials and errors
SO NATURE REVIEWS IMMUNOLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; VACCINE-INDUCED IMMUNITY; VIRAL
SET-POINT; ESCAPE MUTATIONS; CLASS-I; DISEASE PROGRESSION; EPITOPE
VARIANTS; CLINICAL-TRIALS; RHESUS MACAQUES; DOUBLE-BLIND
AB Even before the partial success of a preventive HIV vaccine in a recent Phase III clinical trial, there had been an active research effort to determine one or more immune correlates of protection for HIV infection. This effort has been hampered by the lack of natural protective immunity against HIV. As a result, most of the studies have focused on long-term non-progressive infection or other clinical situations, none of which fully recapitulates protective immunity against HIV. Although this effort has been successful in defining characteristics of T cells in acute and non-progressive HIV infection, and has therefore greatly expanded our knowledge of the immunopathogenesis of AIDS, its success in defining immune correlates of protection is less clear. In this Opinion article we offer a perspective on how successful this effort has been in defining immune correlates of protection that have been, or will be, of use in the development of an HIV vaccine. Our view is that investing in an iterative approach to human vaccine efficacy trials of sufficient size and sampling frequency will improve the likelihood that an immune correlate of vaccine protection will be defined.
C1 [Koup, Richard A.; Graham, Barney S.; Douek, Daniel C.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Douek, DC (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM ddouek@mail.nih.gov
NR 70
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Z9 26
U1 1
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-1733
J9 NAT REV IMMUNOL
JI Nat. Rev. Immunol.
PD JAN
PY 2011
VL 11
IS 1
BP 65
EP 70
DI 10.1038/nri2890
PG 6
WC Immunology
SC Immunology
GA 698DR
UT WOS:000285572600015
PM 21164527
ER
PT J
AU Youle, RJ
Narendra, DP
AF Youle, Richard J.
Narendra, Derek P.
TI Mechanisms of mitophagy
SO NATURE REVIEWS MOLECULAR CELL BIOLOGY
LA English
DT Review
ID MITOCHONDRIAL-DNA DELETIONS; RECESSIVE JUVENILE PARKINSONISM;
SUBSTANTIA-NIGRA NEURONS; RETICULOCYTE MATURATION; PINK1/PARKIN-MEDIATED
MITOPHAGY; AUTOPHAGOSOME BIOGENESIS; ERYTHROID-CELLS; PINK1; DISEASE;
MUTATIONS
AB Autophagy not only recycles intracellular components to compensate for nutrient deprivation but also selectively eliminates organelles to regulate their number and maintain quality control. Mitophagy, the specific autophagic elimination of mitochondria, has been identified in yeast, mediated by autophagy-related 32 (Atg32), and in mammals during red blood cell differentiation, mediated by NIP3-like protein X (NIX; also known as BNIP3L). Moreover, mitophagy is regulated in many metazoan cell types by parkin and PTEN-induced putative kinase protein 1 (PINK1), and mutations in the genes encoding these proteins have been linked to forms of Parkinson's disease.
C1 [Youle, Richard J.; Narendra, Derek P.] NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Narendra, Derek P.] Med Res Council Mitochondrial Biol Unit, Cambridge CB2 2XY, England.
RP Youle, RJ (reprint author), NINDS, Biochem Sect, Surg Neurol Branch, NIH, 35 Convent Dr,2C-917, Bethesda, MD 20892 USA.
EM youler@ninds.nih.gov
FU Intramural NIH HHS [Z99 NS999999]
NR 72
TC 845
Z9 867
U1 51
U2 295
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1471-0072
J9 NAT REV MOL CELL BIO
JI Nat. Rev. Mol. Cell Biol.
PD JAN
PY 2011
VL 12
IS 1
BP 9
EP 14
DI 10.1038/nrm3028
PG 6
WC Cell Biology
SC Cell Biology
GA 697UJ
UT WOS:000285544000009
PM 21179058
ER
PT J
AU Skinner, M
AF Skinner, Mhairi
TI PROTEIN SYNTHESIS An expressive couple
SO NATURE REVIEWS MOLECULAR CELL BIOLOGY
LA English
DT Editorial Material
ID TRANSLATION
C1 NCI, Nat Pathway Interact Database, Bethesda, MD 20892 USA.
RP Skinner, M (reprint author), NCI, Nat Pathway Interact Database, Bethesda, MD 20892 USA.
NR 2
TC 0
Z9 0
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1471-0072
J9 NAT REV MOL CELL BIO
JI Nat. Rev. Mol. Cell Biol.
PD JAN
PY 2011
VL 12
IS 1
DI 10.1038/nrm3037
PG 1
WC Cell Biology
SC Cell Biology
GA 697UJ
UT WOS:000285544000008
PM 21179057
ER
PT J
AU Kaler, SG
AF Kaler, Stephen G.
TI ATP7A-related copper transport diseases-emerging concepts and future
trends
SO NATURE REVIEWS NEUROLOGY
LA English
DT Review
ID OCCIPITAL-HORN-SYNDROME; MARIE-TOOTH-DISEASE; P-TYPE ATPASE; HEREDITARY
MOTOR NEUROPATHY; SPINAL MUSCULAR-ATROPHY; MOTTLED BRINDLED MOUSE;
MENKES-DISEASE; ATP7A GENE; WILSON-DISEASE; CHOROID-PLEXUS
AB This Review summarizes recent advances in understanding copper-transporting ATPase 1 (ATP7A), and examines the neurological phenotypes associated with dysfunction of this protein. Involvement of ATP7A in axonal outgrowth, synapse integrity and neuronal activation underscores the fundamental importance of copper metabolism to neurological function. Defects in ATP7A cause Menkes disease, an infantile-onset, lethal condition. Neonatal diagnosis and early treatment with copper injections enhance survival in patients with this disease, and can normalize clinical outcomes if mutant ATP7A molecules retain small amounts of residual activity. Gene replacement rescues a mouse model of Menkes disease, suggesting a potential therapeutic approach for patients with complete loss-of-function ATP7A mutations. Remarkably, a newly discovered ATP7A disorder-isolated distal motor neuropathy-has none of the characteristic clinical or biochemical abnormalities of Menkes disease or its milder allelic variant occipital horn syndrome (OHS), instead resembling Charcot-Marie-Tooth disease type 2. These findings indicate that ATP7A has a crucial but previously unappreciated role in motor neuron maintenance, and that the mechanism underlying ATP7A-related distal motor neuropathy is distinct from Menkes disease and OHS pathophysiology. Collectively, these insights refine our knowledge of the neurology of ATP7A-related copper transport diseases and pave the way for further progress in understanding ATP7A function.
C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Human Copper Metab, Program Mol Med, NIH, Bethesda, MD 20892 USA.
RP Kaler, SG (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Human Copper Metab, Program Mol Med, NIH, Bldg 10 Room 10N313,10 Ctr Dr MSC 1853, Bethesda, MD 20892 USA.
EM kalers@mail.nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NIH)
FX Written consent was obtained for publication of Figure 2a from the
patient's mother. The author is supported by the Intramural Program of
the Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NIH). The author apologizes to any colleagues whose work
was not cited in this Review as a result of length constraints.
NR 164
TC 156
Z9 157
U1 2
U2 27
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-4758
J9 NAT REV NEUROL
JI Nat. Rev. Neurol.
PD JAN
PY 2011
VL 7
IS 1
BP 15
EP 29
DI 10.1038/nrneurol.2010.180
PG 15
WC Clinical Neurology
SC Neurosciences & Neurology
GA 705AG
UT WOS:000286099300008
PM 21221114
ER
PT J
AU Blackstone, C
O'Kane, CJ
Reid, E
AF Blackstone, Craig
O'Kane, Cahir J.
Reid, Evan
TI Hereditary spastic paraplegias: membrane traffic and the motor pathway
SO NATURE REVIEWS NEUROSCIENCE
LA English
DT Review
ID AMYOTROPHIC-LATERAL-SCLEROSIS; REGULATES SYNAPTIC GROWTH; HEAVY-CHAIN
KIF5A; ENDOPLASMIC-RETICULUM; AXONAL-TRANSPORT; ESCRT MACHINERY; PROTEIN
SPASTIN; RECEPTOR TRAFFICKING; ALS2-DEFICIENT MICE; NUCLEOTIDE EXCHANGE
AB Voluntary movement is a fundamental way in which animals respond to, and interact with, their environment. In mammals, the main CNS pathway controlling voluntary movement is the corticospinal tract, which encompasses connections between the cerebral motor cortex and the spinal cord. Hereditary spastic paraplegias (HSPs) are a group of genetic disorders that lead to a length-dependent, distal axonopathy of fibres of the corticospinal tract, causing lower limb spasticity and weakness. Recent work aimed at elucidating the molecular cell biology underlying the HSPs has revealed the importance of basic cellular processes-especially membrane trafficking and organelle morphogenesis and distribution-in axonal maintenance and degeneration.
C1 [Reid, Evan] Univ Cambridge, Dept Med Genet, Cambridge Inst Med Res, Addenbrookes Hosp, Cambridge CB2 0XY, England.
[O'Kane, Cahir J.] Univ Cambridge, Dept Genet, Cambridge CB2 3EH, England.
[Blackstone, Craig] NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA.
RP Reid, E (reprint author), Univ Cambridge, Dept Med Genet, Cambridge Inst Med Res, Addenbrookes Hosp, Wellcome Trust MRC Bldg, Cambridge CB2 0XY, England.
EM ealr4@cam.ac.uk
RI O'Kane, Cahir/C-4413-2011; Reid, Evan/F-3250-2010;
OI Reid, Evan/0000-0003-1623-7304; O'Kane, Cahir/0000-0002-3488-2078
FU Wellcome Trust [082381, WT081386]; UK Medical Research Council; Tom
Wahlig Stiftung; UK HSP Support Group; National Institute of
Neurological Disorders and Stroke, US National Institutes of Health
FX We are grateful to the members of our laboratories who have contributed
to HSP-related work, and to the many HSP family members who have helped
with our research. We thank T. Wahlig and H. Wahlig for their tireless
work in promoting interactions among HSP researchers, clinicians and
families. E. R. is a Wellcome Trust Senior Research Fellow in Clinical
Science (grant 082381) and is also supported by the UK Medical Research
Council, the Tom Wahlig Stiftung and the UK HSP Support Group. The work
of C.J.O'K. on HSP is funded by Wellcome Trust (grant WT081386). C. B.
is supported by the Intramural Research Program of the National
Institute of Neurological Disorders and Stroke, US National Institutes
of Health.
NR 119
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U1 5
U2 25
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 JAN
PY 2011
VL 12
IS 1
BP 31
EP 42
DI 10.1038/nrn2946
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 696PN
UT WOS:000285453900004
PM 21139634
ER
PT J
AU Morimoto, RI
Driessen, AJM
Hegde, RS
Langer, T
AF Morimoto, Richard I.
Driessen, Arnold J. M.
Hegde, Ramanujan S.
Langer, Thomas
TI The life of proteins: the good, the mostly good and the ugly
SO NATURE STRUCTURAL & MOLECULAR BIOLOGY
LA English
DT Editorial Material
C1 [Morimoto, Richard I.] Northwestern Univ, Dept Mol Biosci, Evanston, IL 60208 USA.
[Morimoto, Richard I.] Rice Inst Biomed Res, Evanston, IL USA.
[Driessen, Arnold J. M.] Univ Groningen, Dept Mol Microbiol, Groningen Biomol Sci, Groningen, Netherlands.
[Driessen, Arnold J. M.] Univ Groningen, Zernike Inst Adv Mat, Inst Biotechnol, Groningen, Netherlands.
[Hegde, Ramanujan S.] NICHHD, US Natl Inst Hlth, Bethesda, MD 20892 USA.
[Langer, Thomas] Univ Cologne, Inst Genet, D-5000 Cologne, Germany.
RP Morimoto, RI (reprint author), Northwestern Univ, Dept Mol Biosci, Evanston, IL 60208 USA.
EM r-morimoto@northwestern.edu
RI Driessen, Arnold/D-1876-2012;
OI Driessen, Arnold J.M./0000-0001-9258-9104; Hegde,
Ramanujan/0000-0001-8338-852X; Langer, Thomas/0000-0003-1250-1462
NR 0
TC 6
Z9 8
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1545-9985
J9 NAT STRUCT MOL BIOL
JI Nat. Struct. Mol. Biol.
PD JAN
PY 2011
VL 18
IS 1
BP 1
EP 4
DI 10.1038/nsmb0111-1
PG 4
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 703GQ
UT WOS:000285966800001
PM 21209622
ER
PT J
AU Mears, JA
Lackner, LL
Fang, SM
Ingerman, E
Nunnari, J
Hinshaw, JE
AF Mears, Jason A.
Lackner, Laura L.
Fang, Shunming
Ingerman, Elena
Nunnari, Jodi
Hinshaw, Jenny E.
TI Conformational changes in Dnm1 support a contractile mechanism for
mitochondrial fission
SO NATURE STRUCTURAL & MOLECULAR BIOLOGY
LA English
DT Article
ID CLATHRIN-MEDIATED ENDOCYTOSIS; DYNAMIN-RELATED GTPASE; IN-VIVO; MEMBRANE
FISSION; STRUCTURAL BASIS; STALK REGION; PROTEIN; DOMAIN; CONSTRICTION;
VISUALIZATION
AB Mitochondria are dynamic organelles that undergo cycles of fission and fusion. The yeast dynamin-related protein Dnm1 has been localized to sites of mitochondrial division. Using cryo-EM, we have determined the three-dimensional (3D) structure of Dnm1 in a GTP-bound state. The 3D map showed that Dnm1 adopted a unique helical assembly when compared with dynamin, which is involved in vesicle scission during endocytosis. Upon GTP hydrolysis, Dnm1 constricted liposomes and subsequently dissociated from the lipid bilayer. The magnitude of Dnm1 constriction was substantially larger than the decrease in diameter previously reported for dynamin. We postulate that the larger conformational change is mediated by a flexible Dnm1 structure that has limited interaction with the underlying bilayer. Our structural studies support the idea that Dnm1 has a mechanochemical role during mitochondrial division.
C1 [Mears, Jason A.; Fang, Shunming; Hinshaw, Jenny E.] NIDDKD, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA.
[Lackner, Laura L.; Ingerman, Elena; Nunnari, Jodi] Univ Calif Davis, Ctr Genet & Dev, Dept Mol & Cellular Biol, Davis, CA 95616 USA.
RP Hinshaw, JE (reprint author), NIDDKD, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA.
EM jennyh@helix.nih.gov
FU US National Institutes of Health (NIH), National Institute of Diabetes
and Digestive and Kidney Diseases (NIDDK); NIH [R01GM062942,
1F32GM078749]
FX We thank D. Winkler and A. Steven for technical assistance in acquiring
tomograms and P. Flicker, J. Hanover, W. Prinz, J. Evans and J. Heymann
for critical discussions and reading of the manuscript. This work was
supported by the Intramural Research Program of the US National
Institutes of Health (NIH), National Institute of Diabetes and Digestive
and Kidney Diseases (NIDDK) (J.E.H.) and the Nancy Nossal Fellowship of
the NIH, NIDDK (J.A.M.). J.N. is supported by NIH grant R01GM062942, and
L.L.L. is supported by NIH postdoctoral fellowship 1F32GM078749.
NR 56
TC 130
Z9 134
U1 2
U2 14
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1545-9985
J9 NAT STRUCT MOL BIOL
JI Nat. Struct. Mol. Biol.
PD JAN
PY 2011
VL 18
IS 1
BP 20
EP +
DI 10.1038/nsmb.1949
PG 8
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 703GQ
UT WOS:000285966800004
PM 21170049
ER
PT J
AU Bugreev, DV
Pezza, RJ
Mazina, OM
Voloshin, ON
Camerini-Otero, RD
Mazin, AV
AF Bugreev, Dmitry V.
Pezza, Roberto J.
Mazina, Olga M.
Voloshin, Oleg N.
Camerini-Otero, R. Daniel
Mazin, Alexander V.
TI The resistance of DMC1 D-loops to dissociation may account for the DMC1
requirement in meiosis
SO NATURE STRUCTURAL & MOLECULAR BIOLOGY
LA English
DT Article
ID DOUBLE-STRAND-BREAK; SYNAPTONEMAL COMPLEX-FORMATION; PROMOTES BRANCH
MIGRATION; BLOOMS-SYNDROME HELICASE; MEIOTIC RECOMBINATION; HOMOLOGOUS
RECOMBINATION; HOLLIDAY JUNCTIONS; SACCHAROMYCES-CEREVISIAE; CHROMOSOME
SYNAPSIS; RAD51 RECOMBINASE
AB The ubiquitously expressed Rad51 recombinase and the meiosis-specific Dmc1 recombinase promote the formation of strand-invasion products (D-loops) between homologous molecules. Strand-invasion products are processed by either the double-strand break repair (DSBR) or synthesis-dependent strand annealing (SDSA) pathway. D-loops destined to be processed by SDSA need to dissociate, producing non-crossovers, and those destined for DSBR should resist dissociation to generate crossovers. The mechanism that channels recombination intermediates into different homologous-recombination pathways is unknown. Here we show that D-loops in a human DMC1-driven reaction are substantially more resistant to dissociation by branch-migration proteins such as RAD54 than those formed by RAD51. We propose that the intrinsic resistance to dissociation of DMC1 strand-invasion intermediates may account for why DMC1 is essential to ensure the proper segregation of chromosomes in meiosis.
C1 [Pezza, Roberto J.; Voloshin, Oleg N.; Camerini-Otero, R. Daniel] NIDDKD, Genet & Biochem Branch, US Natl Inst Hlth, Bethesda, MD 20892 USA.
[Bugreev, Dmitry V.; Mazina, Olga M.; Mazin, Alexander V.] Drexel Univ, Coll Med, Dept Biochem & Mol Biol, Philadelphia, PA 19104 USA.
[Mazin, Alexander V.] Russian Acad Sci, Inst Cytol & Genet, Siberian Branch, Novosibirsk 630090, Russia.
RP Camerini-Otero, RD (reprint author), NIDDKD, Genet & Biochem Branch, US Natl Inst Hlth, Bethesda, MD 20892 USA.
EM rdcamerini@mail.nih.gov; amazin@drexelmed.edu
FU US National Institutes of Health [CA100839, MH084119]; Leukemia and
Lymphoma Society Scholar Award [1054-09]; US National Institute of
Diabetes and Digestive and Kidney Diseases
FX We thank P. Sung (Yale University) and W. Holloman (Cornell University)
for RAD51 and BLM expression vectors, members of the Camerini-Otero and
Mazin labs for comments and discussion, and M. Lichten and P. Hsieh for
critical reading of this manuscript. This work was supported by US
National Institutes of Health grants CA100839 and MH084119, the Leukemia
and Lymphoma Society Scholar Award 1054-09 (to A.V.M.) and the
Intramural Research Program of the US National Institute of Diabetes and
Digestive and Kidney Diseases (to R.D.C.-O.).
NR 60
TC 24
Z9 24
U1 1
U2 7
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1545-9985
J9 NAT STRUCT MOL BIOL
JI Nat. Struct. Mol. Biol.
PD JAN
PY 2011
VL 18
IS 1
BP 56
EP +
DI 10.1038/nsmb.1946
PG 6
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 703GQ
UT WOS:000285966800009
PM 21151113
ER
PT J
AU Jia, L
Yi, XF
Zhang, ZB
Zhuang, ZP
Li, J
Chambers, SK
Kong, BH
Zheng, W
AF Jia, L.
Yi, X. F.
Zhang, Z. B.
Zhuang, Z. P.
Li, J.
Chambers, S. K.
Kong, B. H.
Zheng, W.
TI Prohibitin as a novel target protein of luteinizing hormone in ovarian
epithelial carcinogenesis
SO NEOPLASMA
LA English
DT Article
DE Gonadotropin; Luteinizing hormone; Prohibitin; Ovarian cancer
ID CANCER CELLS; EXPRESSION; PROLIFERATION; RISK; FIBROBLASTS; APOPTOSIS;
SUBTYPES; NUCLEUS; REGION; TUMORS
AB The exact role of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in ovarian epithelial carcinoma (OEC) development has not been yet characterized. This prompted us to identify particular proteins to better understand the underlying mechanism. Total proteins from ovarian epithelial tumor (OET) cells treated with gonadotropins were analyzed by proteomics. Western blot and immunohistochemistry were used to validate the target protein (prohibitin) and to detect its expression in human ovarian tissue of serous tumors. As the results, prohibitin was found to be significantly up-regulated by LH, with a maximum of 2.5-fold increase at the concentration of 200 mIU/mL. The expression of prohibitin was steadily decreased from benign serous cystadenomas to borderline tumors and serous carcinomas (P < 0.0001). The difference between any two groups was significant (P < 0.001). Collectively, data from this study indicate that prohibitin is one LH-associated protein and it may be protective of ovarian cancer development and progression, supporting that LH may play an inhibitory role in ovarian tumorigenesis.
C1 [Jia, L.; Kong, B. H.; Zheng, W.] Shandong Univ, Qilu Hosp, Dept Obstet & Gynecol, Jinan 250012, Peoples R China.
[Yi, X. F.] Fudan Univ, Hosp Obstet & Gynecol, Shanghai 200433, Peoples R China.
[Zhang, Z. B.] Jiao Tong Univ, Shanghai Municipal Hosp 1, Dept Obstet & Gynecol, Shanghai, Peoples R China.
[Zhuang, Z. P.; Li, J.] Natl Inst Neurol Disorders & Stroke, Mol Pathogenesis Unit, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Jia, L.; Chambers, S. K.; Zheng, W.] Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA.
[Zheng, W.] Univ Arizona, Coll Med, Dept Pathol, Tucson, AZ 85721 USA.
[Zheng, W.] Univ Arizona, Coll Med, Dept Obstet & Gynecol, Tucson, AZ 85721 USA.
RP Jia, L (reprint author), Shandong Univ, Qilu Hosp, Dept Obstet & Gynecol, Jinan 250012, Peoples R China.
EM kongbeihua@sdu.edu.cn; zhengw@email.arizona.edu
FU National Natural Science Foundation of China [30901590]; Arizona Cancer
Center [P30 CA23074]; University of Arizona Department of Pathology
FX Dr. Lin Jia was a co-trained PhD candidate of Shandong University,
China. The work was supported partly by the National Natural Science
Foundation of China (No. 30901590) to LJ, Arizona Cancer Center Core
Grant (P30 CA23074), Arizona Cancer Center Better Than Ever Grant, and
University of Arizona Department of Pathology start up fund to WZ. We
thank Dr. Jun Wang at Tufts University (Boston, Massachusetts) for her
excellent statistical data analysis for this project.
NR 30
TC 9
Z9 11
U1 0
U2 3
PU VEDA, SLOVAK ACAD SCIENCES
PI BRASTISLAVA
PA DUBRAVSKA CESTA 9, 842 34 BRASTISLAVA, SLOVAKIA
SN 0028-2685
J9 NEOPLASMA
JI Neoplasma
PY 2011
VL 58
IS 2
BP 104
EP 109
DI 10.4149/neo_2011_02_104
PG 6
WC Oncology
SC Oncology
GA 765HI
UT WOS:000290695700002
PM 21275458
ER
PT J
AU O'Seaghdha, CM
Fox, CS
AF O'Seaghdha, Conall M.
Fox, Caroline S.
TI Genetics of Chronic Kidney Disease
SO NEPHRON CLINICAL PRACTICE
LA English
DT Article
DE Chronic kidney disease; Genetic variation; Genome-wide association
studies; Diabetic nephropathy; End-stage renal disease
ID STAGE RENAL-DISEASE; MANGANESE SUPEROXIDE-DISMUTASE; TYPE-2
DIABETIC-PATIENTS; GENOME-WIDE ASSOCIATION; INCIDENT DIALYSIS PATIENTS;
URINARY ALBUMIN EXCRETION; AFRICAN-AMERICANS; FECHTNER-SYNDROME; IGA
NEPHROPATHY; FAMILIAL PREDISPOSITION
AB The current review collates what is already known of the genetics of chronic kidney disease (CKD), and focuses on new trends in genome-wide assessment of the inherited component of susceptibility to this condition. Early efforts to identify kidney disease susceptibility genetic loci using linkage and candidate gene strategies proved disappointing. More recently, genome-wide association studies have yielded highly promising results suggesting a number of potential candidate genes and genomic regions that may contribute to the pathogenesis of CKD. Renal failure susceptibility genes identified by these methods, such as MYH9, have yielded novel insights into the pathogenesis of CKD. Genome-wide association studies of CKD are beginning to define the genomic architecture of kidney disease and will impact our understanding of how genetic variation influences susceptibility to this condition. Copyright (C) 2010 S. Karger AG, Basel
C1 [O'Seaghdha, Conall M.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[O'Seaghdha, Conall M.] Massachusetts Gen Hosp, Brigham & Womens Hosp, Div Renal, Boston, MA 02114 USA.
[O'Seaghdha, Conall M.; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA.
RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.
EM foxca@nhlbi.nih.gov
NR 88
TC 8
Z9 8
U1 0
U2 4
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 1660-2110
J9 NEPHRON CLIN PRACT
JI Nephron. Clin. Pract.
PY 2011
VL 118
IS 1
BP C55
EP C63
DI 10.1159/000320905
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA 679JD
UT WOS:000284156800009
PM 21071974
ER
PT J
AU Basselin, M
Ramadan, E
Chen, M
Rapoport, SI
AF Basselin, Mireille
Ramadan, Epolia
Chen, Mei
Rapoport, Stanley I.
TI Anti-Inflammatory Effects of Chronic Aspirin on Brain Arachidonic Acid
Metabolites (Retracted article. See vol. 40, pg. 1094, 2015)
SO NEUROCHEMICAL RESEARCH
LA English
DT Article; Retracted Publication
DE Aspirin; Neuroinflammation; Eicosanoids; Arachidonic acid; Lipoxin A(4);
15-epi-lipoxin A(4)
ID LOW-DOSE ASPIRIN; FACTOR-KAPPA-B; LIPOXIN A(4); RAT-BRAIN; TRIGGERED
15-EPI-LIPOXINS; CYCLOOXYGENASE ISOZYMES; ALZHEIMERS-DISEASE;
GENE-EXPRESSION; LEUKOTRIENE B-4; EICOSANOIDS
AB Pro-inflammatory and anti-inflammatory mediators derived from arachidonic acid (AA) modulate peripheral inflammation and its resolution. Aspirin (ASA) is a unique non-steroidal anti-inflammatory drug, which switches AA metabolism from prostaglandin E-2 (PGE(2)) and thromboxane B-2 (TXB2) to lipoxin A(4) (LXA(4)) and 15-epi-LXA(4). However, it is unknown whether chronic therapeutic doses of ASA are anti-inflammatory in the brain. We hypothesized that ASA would dampen increases in brain concentrations of AA metabolites in a rat model of neuroinflammation, produced by a 6-day intracerebroventricular infusion of bacterial lipopolysaccharide (LPS). In rats infused with LPS (0.5 ng/h) and given ASA-free water to drink, concentrations in high-energy microwaved brain of PGE(2), TXB2 and leukotriene B-4 (LTB4) were elevated. In rats infused with artificial cerebrospinal fluid, 6 weeks of treatment with a low (10 mg/kg/day) or high (100 mg/kg/day) ASA dose in drinking water decreased brain PGE(2), but increased LTB4, LXA(4) and 15-epi-LXA(4) concentrations. Both doses attenuated the LPS effects on PGE(2), and TXB2. The increments in LXA(4) and 15-epi-LXA(4) caused by high-dose ASA were significantly greater in LPS-infused rats. The ability of ASA to increase anti-inflammatory LXA(4) and 15-epi-LXA(4) and reduce pro-inflammatory PGE(2) and TXB2 suggests considering aspirin further for treating clinical neuroinflammation.
C1 [Basselin, Mireille; Ramadan, Epolia; Chen, Mei; Rapoport, Stanley I.] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
RP Ramadan, E (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bldg 9,Room 1S126,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM ramadanir@mail.nih.gov
FU National Institute on Aging, NIH
FX This work was supported entirely by the Intramural Research Program of
the National Institute on Aging, NIH. None of the authors has a
financial or other conflict of interest related to this work.
NR 63
TC 17
Z9 18
U1 1
U2 8
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0364-3190
EI 1573-6903
J9 NEUROCHEM RES
JI Neurochem. Res.
PD JAN
PY 2011
VL 36
IS 1
BP 139
EP 145
DI 10.1007/s11064-010-0282-4
PG 7
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 711KA
UT WOS:000286589000017
PM 20981485
ER
PT J
AU Kaminski, RM
Nunez-Taltavull, JF
Budziszewska, B
Lason, W
Gasior, M
Zapata, A
Shippenberg, TS
Witkin, JM
AF Kaminski, Rafal M.
Nunez-Taltavull, Juan F.
Budziszewska, Boguslawa
Lason, Wladyslaw
Gasior, Maciej
Zapata, Agustin
Shippenberg, Toni S.
Witkin, Jeffrey M.
TI Effects of Cocaine-Kindling on the Expression of NMDA Receptors and
Glutamate Levels in Mouse Brain
SO NEUROCHEMICAL RESEARCH
LA English
DT Article
DE Cocaine; Seizure; Kindling; Glutamate; Microdialysis; NMDA receptor
ID METHYL-D-ASPARTATE; EXCITATORY AMINO-ACIDS; IN-VIVO MICRODIALYSIS;
EXTRACELLULAR GLUTAMATE; INDUCED CONVULSIONS; REVERSE TOLERANCE; RAT;
HIPPOCAMPUS; ANTAGONISTS; MICE
AB In the present study we examined the effects of cocaine seizure kindling on the expression of NMDA receptors and levels of extracellular glutamate in mouse brain. Quantitative autoradiography did not reveal any changes in binding of [(3)H] MK-801 to NMDA receptors in several brain regions. Likewise, in situ hybridization and Western blotting revealed no alteration in expression of the NMDA receptor subunits, NR1 and NR2B. Basal overflow of glutamate in the ventral hippocampus determined by microdialysis in freely moving animals also did not differ between cocaine-kindled and control groups. Perfusion with the selective excitatory amino acid transporter inhibitor, pyrrolidine-2,4-dicarboxylic acid (tPDC, 0.6 mM), increased glutamate overflow confirming transport inhibition. Importantly, KCl-evoked glutamate overflow under tPDC perfusion was significantly higher in cocaine-kindled mice than in control mice. These data suggest that enhancement of depolarization stimulated glutamate release may be one of the mechanisms underlying the development of increased seizure susceptibility after cocaine kindling.
C1 [Kaminski, Rafal M.] UCB Pharma SA, CNS Res, Epilepsy Pharmacol, B-1420 Braine I Alleud, Belgium.
[Kaminski, Rafal M.; Gasior, Maciej; Witkin, Jeffrey M.] Natl Inst Drug Abuse, Drug Dev Grp, Behav Neurosci Branch, NIH, Baltimore, MD 21224 USA.
[Kaminski, Rafal M.; Nunez-Taltavull, Juan F.; Zapata, Agustin; Shippenberg, Toni S.] Natl Inst Drug Abuse, Integrat Neurosci Sect, Behav Neurosci Branch, NIH, Baltimore, MD 21224 USA.
[Budziszewska, Boguslawa; Lason, Wladyslaw] Polish Acad Sci, Inst Pharmacol, Dept Expt Neuroendocrinol, Krakow, Poland.
RP Kaminski, RM (reprint author), UCB Pharma SA, CNS Res, Epilepsy Pharmacol, Chemin Foriest,R9, B-1420 Braine I Alleud, Belgium.
EM rafal.kaminski@ucb.com
FU NIDA, NIH
FX This research was supported by NIDA Intramural Research Program of NIH.
NR 37
TC 8
Z9 8
U1 1
U2 5
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0364-3190
J9 NEUROCHEM RES
JI Neurochem. Res.
PD JAN
PY 2011
VL 36
IS 1
BP 146
EP 152
DI 10.1007/s11064-010-0284-2
PG 7
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 711KA
UT WOS:000286589000018
PM 20927585
ER
PT J
AU Holl, AK
Ille, R
Wilkinson, L
Otti, DV
Hodl, E
Herranhof, B
Reisinger, KM
Muller, N
Painold, A
Holl, EM
Letmaier, M
Bonelli, RM
AF Holl, Anna K.
Ille, Rottraut
Wilkinson, Leonora
Otti, Daniela V.
Hoedl, Elfriede
Herranhof, Brigitte
Reisinger, Karin M.
Mueller, Nicole
Painold, Annamaria
Holl, Etienne M.
Letmaier, Martin
Bonelli, Raphael M.
TI Impaired Ideomotor Limb Apraxia in Cortical and Subcortical Dementia: A
Comparison of Alzheimer's and Huntington's Disease
SO NEURODEGENERATIVE DISEASES
LA English
DT Article
DE Huntington's disease; Alzheimer's disease; Apraxia; Neuropsychological
assessment
ID PROGRESSIVE SUPRANUCLEAR PALSY; PARKINSONS-DISEASE; IMITATING GESTURES;
BASAL GANGLIA; MOTOR; CORTEX; PATHOPHYSIOLOGY; MOVEMENTS; PRAXIS; SCALE
AB Background: Although ideomotor limb apraxia is often considered to occur only in dementia with cortical involvement like Alzheimer's disease (AD), it is also frequently seen in dementia with subcortical degeneration like Huntington's disease (HD). Methods: To assess the occurrence of ideomotor limb apraxia, 46 patients with HD (27 men) and 37 patients with AD (16 men), matched for cognitive performance, were assessed with an apraxia test battery containing tests of the imitation of meaningless hand and finger gestures, the performance of meaningful gestures and of pantomimic movements. Results: There was a high frequency of ideomotor limb apraxia in both AD and HD patients. For the assessment of hands' imitation 13.5% of the AD patients and 41.3% of the HD patients were apraxic, for fingers' imitation 21.6% (AD) and 41.3% (HD) were apraxic, for gestures 27.0% (AD) and 32.6% (HD), and for the assessment of pantomimic movements 24.3% (AD) and 52.2% (HD) showed apraxia. In the AD patients, disease severity was related to the occurrence of apraxia. Conclusions: Ideomotor limb apraxia is a common sign in both groups of patients, occurring in a high percentage. For particular neuropsychological deficits, including ideomotor limb apraxia, a division of dementia in a subcortical and cortical subtype seems to be clinically not meaningful. Copyright (C) 2011 S. Karger AG, Basel
C1 [Holl, Anna K.; Otti, Daniela V.; Herranhof, Brigitte; Reisinger, Karin M.; Mueller, Nicole; Painold, Annamaria; Letmaier, Martin] Graz Med Univ, Univ Clin Psychiat, Dept Psychiat, AT-8036 Graz, Austria.
[Holl, Etienne M.] Graz Med Univ, Dept Neurosurg, AT-8036 Graz, Austria.
[Ille, Rottraut] Karl Franzens Univ Graz, Inst Psychol, Graz, Austria.
[Hoedl, Elfriede] Krankenhaus Barmherzigen Bruder Graz Eggenberg, Dept Neurol & Psychiat, Graz, Austria.
[Bonelli, Raphael M.] Paracelsus Med Univ, Dept Neurol, Salzburg, Austria.
[Wilkinson, Leonora] Natl Inst Neurol Disorders & Stroke, Brain Stimulat Unit, Bethesda, MD USA.
RP Holl, AK (reprint author), Graz Med Univ, Univ Clin Psychiat, Dept Psychiat, Auenbruggerpl 31, AT-8036 Graz, Austria.
EM anna.holl@klinikum-graz.at
FU Parkinson's UK [F-0608]
NR 45
TC 5
Z9 6
U1 1
U2 4
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 1660-2854
J9 NEURODEGENER DIS
JI Neurodegener. Dis.
PY 2011
VL 8
IS 4
BP 208
EP 215
DI 10.1159/000322230
PG 8
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 763LT
UT WOS:000290559000007
PM 21212634
ER
PT J
AU Gao, JJ
Xu, H
Weinberg, C
Huang, XM
Park, Y
Hollenbeck, A
Blair, A
Schatzkin, A
Burch, L
Chen, HL
AF Gao, Jianjun
Xu, Hong
Weinberg, Clarice
Huang, Xuemei
Park, Yikyung
Hollenbeck, Albert
Blair, Aaron
Schatzkin, Arthur
Burch, Lauranell
Chen, Honglei
TI An Exploratory Study on the CHRNA3-CHRNA5-CHRNB4 Cluster, Smoking, and
Parkinson's Disease
SO NEURODEGENERATIVE DISEASES
LA English
DT Article
DE Parkinson's disease; Smoking; CHRNA3-CHRNA5-CHRNB4 cluster; Nicotine
dependence
ID LUNG-CANCER; SUSCEPTIBILITY LOCUS; NICOTINIC RECEPTORS; TARGETS; RISK
AB Background: Smokers have a lower risk of Parkinson's disease (PD). Recent genome-wide association studies (GWAS) have consistently linked several single nucleotide polymorphisms (SNPs) in the CHRNA3-CHRNA5-CHRNB4 cluster on chromosome 15.q25 to smoking behaviors and nicotine dependence. Investigations into these SNPs may help explain the nature and mechanisms of the smoking-PD relationship. Objective: To examine whether the genetic variations that were consistently associated with smoking or nicotine dependence in recent GWAS also predict the risk of PD. Methods: This is a population-based case-control study of 788 physician-diagnosed PD patients and 911 controls, all non-Hispanic Whites. Seven SNPs were selected based on findings from recent GWAS on smoking and nicotine dependence, all from the nicotinic acetylcholine receptor subunits (CHRN) A3-A5-B4. Odds ratios (ORs) and 95% confidence intervals were derived from logistic regression models under the assumption of logit-additive allelic effects. Results: Four SNPs in linkage disequilibrium from the CHRNA3-CHRNA5-CHRNB4 cluster were associated with smoking duration (OR >1.3, p < 0.05). However, none of the SNPs from this cluster was associated with PD risk in the overall analysis or after stratifying on smoking status. Conclusion: This preliminary analysis does not support a relationship between these smoking-related GWAS SNPs and PD. Copyright (C) 2011 S. Karger AG, Basel
C1 [Gao, Jianjun; Chen, Honglei] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
[Xu, Hong; Burch, Lauranell] NIEHS, Mol Genet Core Facil, Res Triangle Pk, NC 27709 USA.
[Weinberg, Clarice] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA.
[Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Neurol, Hershey, PA 17033 USA.
[Park, Yikyung; Schatzkin, Arthur] NCI, Nutr Epidemiol Branch, Rockville, MD USA.
[Blair, Aaron] NCI, Occupat & Environm Epidemiol Branch, Rockville, MD USA.
[Hollenbeck, Albert] AARP, Washington, DC USA.
RP Chen, HL (reprint author), NIEHS, Epidemiol Branch, 111 TW Alexander Dr,POB 12233,Mail Drop A3-05, Res Triangle Pk, NC 27709 USA.
EM chenh2@niehs.nih.gov
OI Xu, Hong/0000-0003-1995-4675; Chen, Honglei/0000-0003-3446-7779; Park,
Yikyung/0000-0002-6281-489X
FU NIH [R01 NS060722]; National Institute of Environmental Health Sciences
[Z01-ES-101986]; National Cancer Institute [Z01 CP010196-02]
FX The authors are grateful to the continuous contribution of the NIH-AARP
Diet and Health Study participants. We also thank Drs. Dana Hancock and
Min Shi for their comments on the manuscript. This study was supported
by the intramural research program of the NIH, the National Institute of
Environmental Health Sciences (Z01-ES-101986), the National Cancer
Institute (Z01 CP010196-02), and an NIH extramural grant (R01 NS060722)
to Dr. Huang.
NR 11
TC 3
Z9 3
U1 0
U2 3
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 1660-2854
J9 NEURODEGENER DIS
JI Neurodegener. Dis.
PY 2011
VL 8
IS 5
BP 296
EP 299
DI 10.1159/000323190
PG 4
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 776MH
UT WOS:000291538700004
PM 21228559
ER
PT J
AU Li, XR
Kumar, A
Lee, C
Tang, ZS
Li, Y
Arjunan, P
Hou, X
Zhang, F
AF Li, Xuri
Kumar, Anil
Lee, Chunsik
Tang, Zhongshu
Li, Yang
Arjunan, Pachiappan
Hou, Xu
Zhang, Fan
BE Chang, RCC
TI Can VEGF-B Be Used to Treat Neurodegenerative Diseases?
SO NEURODEGENERATIVE DISEASES - PROCESSES, PREVENTION, PROTECTION AND
MONITORING
LA English
DT Article; Book Chapter
ID ENDOTHELIAL GROWTH-FACTOR; MODERATE ALZHEIMERS-DISEASE;
PARKINSONS-DISEASE; HUNTINGTONS-DISEASE; IN-VIVO; MACULAR DEGENERATION;
TRANSGENIC MICE; DOPAMINERGIC-NEURONS; DIABETIC-RETINOPATHY;
FAMILY-MEMBERS
C1 [Li, Xuri; Kumar, Anil; Lee, Chunsik; Tang, Zhongshu; Li, Yang; Arjunan, Pachiappan; Hou, Xu; Zhang, Fan] NEI, NIH, Rockville, MD 20892 USA.
RP Li, XR (reprint author), NEI, NIH, Rockville, MD 20892 USA.
NR 117
TC 0
Z9 0
U1 0
U2 0
PU INTECH EUROPE
PI RIJEKA
PA JANEZA TRDINE9, RIJEKA, 51000, CROATIA
BN 978-953-307-485-6
PY 2011
BP 387
EP 406
D2 10.5772/1252
PG 20
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA BG1KI
UT WOS:000386854400017
ER
PT J
AU Stranahan, AM
Arumugam, TV
Mattson, MP
AF Stranahan, Alexis M.
Arumugam, Thiruma V.
Mattson, Mark P.
TI Lowering Corticosterone Levels Reinstates Hippocampal Brain-Derived
Neurotropic Factor and Trkb Expression without Influencing Deficits in
Hypothalamic Brain-Derived Neurotropic Factor Expression in Leptin
Receptor-Deficient Mice
SO NEUROENDOCRINOLOGY
LA English
DT Article
DE Diabetes; Glucocorticoid; Neurotropic factor; Hippocampus; Hypothalamus
ID SYNAPTIC PLASTICITY; DIABETIC MICE; OBESITY; BDNF; METABOLISM; NEURONS;
MOUSE
AB Background/Aims: Changes in the glucocorticoid milieu contribute to alterations in neurotropic factor expression across multiple brain regions. Insulin-resistant diabetes is often accompanied by dysregulation of adrenal steroid production in humans and animal models. Leptin receptor-deficient mice (db/db) show reduced expression of brain-derived neurotropic factor (BDNF) in the hippocampus and increases in circulating corticosterone levels, but the extent to which elevated corticosterone levels mediate deficits in BDNF expression has not been determined. Methods: Using in situ hybridization, we measured the expression of BDNF, its receptor TrkB, and neurotropin-3 (NT-3) in the hippocampus and hypothalamus of db/db mice and wild-type controls following adrenalectomy and low-dose corticosterone replacement (ADX+CORT) or sham operation. Results: Lowering corticosterone levels restored BDNF and TrkB expression in the hippocampus of db/db mice. However, deficits in hypothalamic BDNF expression were not reversed following ADX+CORT. There was no effect of genotype or adrenalectomy on NT-3 expression in any brain region examined. Conclusion: Leptin receptor-deficient mice exhibit reduced BDNF expression in the hippocampus and hypothalamus. In the db/db mouse hippocampus, suppression of BDNF occurs in a glucocorticoid-dependent fashion, while hypothalamic BDNF expression is reduced via glucocorticoid-independent mechanisms. Region-specific signals therefore play a role in the interaction between corticosteroids and neurotropic factor expression. Copyright (C) 2010 S. Karger AG, Basel
C1 [Stranahan, Alexis M.] Johns Hopkins Univ, Dept Psychol & Brain Sci, Baltimore, MD 21218 USA.
[Stranahan, Alexis M.; Arumugam, Thiruma V.; Mattson, Mark P.] NIA, Cellular & Mol Neurosci Sect, Lab Neurosci, Baltimore, MD 21224 USA.
RP Stranahan, AM (reprint author), Johns Hopkins Univ, Dept Psychol & Brain Sci, 3400 N Charles St, Baltimore, MD 21218 USA.
EM astrana1@jhu.edu
RI Arumugam, Thiruma/B-4898-2011; Mattson, Mark/F-6038-2012
FU Ford Foundation; National Institute on Aging
FX This work was supported by a Ford Foundation Fellowship to A.M.S., and
by the National Institute on Aging Intramural Research Program. We are
grateful to Rebecca Haberman for insightful suggestions and Michela
Gallagher for use of resources for the in situ hybridization
experiments.
NR 21
TC 17
Z9 17
U1 1
U2 6
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0028-3835
J9 NEUROENDOCRINOLOGY
JI Neuroendocrinology
PY 2011
VL 93
IS 1
BP 58
EP 64
DI 10.1159/000322808
PG 7
WC Endocrinology & Metabolism; Neurosciences
SC Endocrinology & Metabolism; Neurosciences & Neurology
GA 721IX
UT WOS:000287347900007
PM 21160171
ER
PT J
AU Schraml, FV
Goslar, PW
Baxter, L
Beason-Held, LL
AF Schraml, Frank V.
Goslar, Pamela W.
Baxter, Leslie
Beason-Held, Lori L.
TI Thyroid stimulating hormone and cognition during severe, transient
hypothyroidism
SO NEUROENDOCRINOLOGY LETTERS
LA English
DT Article
DE thyroid stimulating hormone; cognition; hypothyroidism; depression;
working memory
ID CEREBRAL-BLOOD-FLOW; RAT-BRAIN; MOOD DISORDERS; TRIIODOTHYRONINE;
DEPRESSION; MEMORY
AB OBJECTIVE: The purpose of our pilot study was to explore the relationship between serum thyroid stimulating hormone (TSH) levels during overt hypothyroidism (OH) and hypothyroid-related neuropsychological symptoms. We hypothesized that TSH level may reflect the degree of 'brain hypothyroidism' such that an inverse correlation may exist between serum TSH and cognitive function in patients experiencing overt hypothyroidism (OH), and sought to explore this hypothesis.
METHODS: Eleven thyroidectomized patients underwent neuropsychological and thyroid function testing while overtly hypothyroid, and again following thyroid hormone replacement. Their test performance was compared with that of eleven healthy controls at a similarly separated two points in time, and the change over time for the patient group and the controls was likewise assessed and compared. The patients' neuropsychological test scores were then correlated with their serum TSH levels while hypothyroid.
RESULTS: The patients' performance while hypothyroid was worse than that of the controls in only one neurocognitive measure - Working Memory Index. The subjects improved similarly or to a greater degree than the controls, when the subjects were thyroid hormone replaced, on all but one neurocognitive measure - Thurstone Word Fluency. TSH level during hypothyroidism was inversely proportional to the patients' performance on these same two measures, but no others.
CONCLUSION: Serum TSH level during hypothyroidism was inversely proportional to performance on the only two neurocognitive measures evidencing an adverse effect from hypothyroidism in our cohort. This suggests thatserum TSH level may reflect the severity of 'brain hypothyroidism' during the overt stage of this condition.
C1 [Schraml, Frank V.] St Josephs Hosp, Barrow Neurol Inst, Dept Radiol, Phoenix, AZ 85013 USA.
[Schraml, Frank V.] St Josephs Hosp, Barrow Neurol Inst, Dept Psychiat, Phoenix, AZ 85013 USA.
[Beason-Held, Lori L.] NIA, Lab Personal & Cognit, NIH, Baltimore, MD 21224 USA.
RP Schraml, FV (reprint author), St Josephs Hosp, Barrow Neurol Inst, Dept Radiol, 350 W Thomas Rd, Phoenix, AZ 85013 USA.
EM fvschraml@yahoo.com
FU NIH, National Institute on Aging
FX Dr. Beason-Held's work was supported by the Intramural Research Program
of the NIH, National Institute on Aging. The opinions expressed in this
work are those of the authors, and do not reflect the official policy or
the position of the U.S. Department of the Navy, U.S. Department of
Defense, or the U.S. government.
NR 31
TC 7
Z9 7
U1 0
U2 2
PU MAGHIRA & MAAS PUBLICATIONS
PI STOCKHOLM
PA PO BOX 26132, S-100 41 STOCKHOLM, SWEDEN
SN 0172-780X
J9 NEUROENDOCRINOL LETT
JI Neuroendocrinol. Lett.
PY 2011
VL 32
IS 3
BP 279
EP 285
PG 7
WC Endocrinology & Metabolism; Neurosciences
SC Endocrinology & Metabolism; Neurosciences & Neurology
GA 809XJ
UT WOS:000294089700011
PM 21712772
ER
PT J
AU Jefferson, AL
Massaro, JM
Beiser, AS
Seshadri, S
Larson, MG
Wolf, PA
Au, R
Benjamin, EJ
AF Jefferson, Angela L.
Massaro, Joseph M.
Beiser, Alexa S.
Seshadri, Sudha
Larson, Martin G.
Wolf, Philip A.
Au, Rhoda
Benjamin, Emelia J.
TI Inflammatory Markers and Neuropsychological Functioning: The Framingham
Heart Study
SO NEUROEPIDEMIOLOGY
LA English
DT Article
DE Memory; Executive functioning; Inflammation; Cognition; WRAT-3 reading
ID C-REACTIVE PROTEIN; STROKE RISK PROFILE; ALZHEIMERS-DISEASE; COGNITIVE
DECLINE; AFRICAN-AMERICAN; TEST-PERFORMANCE; CARDIOVASCULAR-DISEASE;
READING LEVEL; WHITE ELDERS; BRAIN VOLUME
AB Background/Aims: We hypothesized that inflammatory markers are cross-sectionally and longitudinally associated with neuropsychological indicators of early ischemia and Alzheimer's disease. Methods: Framingham Offspring Study participants, free of clinical stroke or dementia (n = 1,878; 60 +/- 9 years; 54% women), underwent neuropsychological assessment and ascertainment of 11 inflammatory markers. Follow-up neuropsychological assessments (6.3 +/- 1.0 years) were conducted on 1,352 of the original 1,878 participants. Results: Multivariable linear regression related the inflammatory markers to cross-sectional performance and longitudinal change in neuropsychological performances. Secondary models included a twelfth factor, tumor necrosis factor-alpha (TNF-alpha), available on a subset of the sample (n = 1,393 cross-sectional; n = 1,213 longitudinal). Results suggest a few modest cross-sectional inflammatory and neuropsychological associations, particularly for tests assessing visual organization (C-reactive protein, p = 0.007), and a few modest relations between inflammatory markers and neuropsychological change, particularly for executive functioning (TNF-alpha, p = 0.004). Secondary analyses suggested that inflammatory markers were cross-sectionally (TNF-alpha, p = 0.004) related to reading performance. Conclusions: Our findings are largely negative, but suggest that specific inflammatory markers may have limited associations with poorer cognition and reading performance among community-dwelling adults. Because of multiple testing concerns, our limited positive findings are offered as hypothesis generating and require replication in other studies. Copyright (C) 2011 S. Karger AG, Basel
C1 [Jefferson, Angela L.] Boston Univ, Sch Med, Alzheimers Dis Ctr, Boston, MA 02118 USA.
[Massaro, Joseph M.; Beiser, Alexa S.; Larson, Martin G.; Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Boston, MA USA.
[Massaro, Joseph M.; Beiser, Alexa S.; Seshadri, Sudha; Larson, Martin G.; Wolf, Philip A.; Au, Rhoda; Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
RP Jefferson, AL (reprint author), Boston Univ, Sch Med, Alzheimers Dis Ctr, 72 E Concord St,B-7800, Boston, MA 02118 USA.
EM angelaj@bu.edu
OI Massaro, Joseph/0000-0002-2682-4812; Larson, Martin/0000-0002-9631-1254;
Seshadri, Sudha/0000-0001-6135-2622; Au, Rhoda/0000-0001-7742-4491;
Benjamin, Emelia/0000-0003-4076-2336; Beiser, Alexa/0000-0001-8551-7778
NR 49
TC 18
Z9 18
U1 0
U2 4
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0251-5350
J9 NEUROEPIDEMIOLOGY
JI Neuroepidemiology
PY 2011
VL 37
IS 1
BP 21
EP 30
DI 10.1159/000328864
PG 10
WC Public, Environmental & Occupational Health; Clinical Neurology
SC Public, Environmental & Occupational Health; Neurosciences & Neurology
GA 811NF
UT WOS:000294217300004
PM 21757961
ER
PT J
AU Granert, O
Peller, M
Gaser, C
Groppa, S
Hallett, M
Knutzen, A
Deuschl, G
Zeuner, KE
Siebner, HR
AF Granert, Oliver
Peller, Martin
Gaser, Christian
Groppa, Sergiu
Hallett, Mark
Knutzen, Arne
Deuschl, Guenther
Zeuner, Kirsten E.
Siebner, Hartwig R.
TI Manual activity shapes structure and function in contralateral human
motor hand area
SO NEUROIMAGE
LA English
DT Article
DE Cortical plasticity; Focal dystonia; Human motor cortex; Immobilization;
Magnetic resonance imaging; Motor training; Transcranial magnetic
stimulation; Voxel based morphometry
ID TRANSCRANIAL MAGNETIC STIMULATION; VOXEL-BASED MORPHOMETRY; WRITERS
CRAMP; WHITE-MATTER; LIMB IMMOBILIZATION; CORTEX EXCITABILITY;
HUNTINGTONS-DISEASE; ADULT CORTEX; BRAIN; PLASTICITY
AB From longitudinal voxel-based morphometry (VBM) studies we know that relatively short periods of training can increase regional grey matter volume in trained cortical areas. In 14 right-handed patients with writer's cramp, we employed VBM to test whether suppression (i.e., immobilization) or enhancement (i.e., training) of manual activity lead to opposing changes in grey matter in the contralateral primary motor hand area (M1(HAND)). We additionally used transcranial magnetic stimulation (TMS) to evaluate concurrent changes in regional excitability. Patients were recruited from a clinical trial which was designed to improve handwriting-associated dystonia. Initially the dystonic hand was immobilized for 4 weeks with the intention to reverse faulty plasticity. After immobilization, patients accomplished a motor re-training for 8 weeks. T1-weighted MRIs of the whole brain and single-pulse TMS measurements of the resting motor threshold (RMT) were performed every 4 weeks. Immobilization of the right hand resulted in a relative grey matter decrease in the contralateral left M1(HAND) along with a decrease in corticomotor excitability as indexed by an increase in RMT. Subsequent training reversed the effects of immobilization, causing an increase in regional grey matter density and excitability of left M1(HAND). The relative changes in grey matter correlated with the relative shifts in RMT. This prospective within-subject VBM study in task-specific hand dystonia shows that the grey matter density of M1(HAND) is dynamically shaped by the level of manual activity. This bi-directional structural plasticity is functionally relevant as local grey matter changes are mirrored by changes in regional excitability. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Granert, Oliver; Peller, Martin; Groppa, Sergiu; Knutzen, Arne; Deuschl, Guenther; Zeuner, Kirsten E.; Siebner, Hartwig R.] Univ Kiel, Dept Neurol, D-24105 Kiel, Germany.
[Gaser, Christian] Univ Jena, Dept Psychiat, Jena, Germany.
[Hallett, Mark] Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD USA.
[Siebner, Hartwig R.] NeuroImageNord, Hamburg, Germany.
[Siebner, Hartwig R.] Univ Copenhagen, Hvidovre Hosp, Danish Res Ctr Magnet Resonance, DK-2650 Hvidovre, Denmark.
[Siebner, Hartwig R.] Univ Copenhagen, Dept Neurol Psychiat & Senses, Fac Med, Copenhagen, Denmark.
RP Granert, O (reprint author), Univ Kiel, Dept Neurol, Arnold Heller Str 3,Haus 41, D-24105 Kiel, Germany.
EM o.granert@neurologie.uni-kiel.de
RI Gaser, Christian/F-5103-2010; Groppa, Sergiu/G-4606-2014; Deuschl,
Gunther/A-7986-2010; Siebner, Hartwig/G-4052-2016;
OI Gaser, Christian/0000-0002-9940-099X; Granert,
Oliver/0000-0002-0656-1023
FU Deutsche Forschungsgemeinschaft [DE 438/7, 7-2]; BMBF [01GO 0511]
FX This study was supported by a project grant from the Deutsche
Forschungsgemeinschaft (DE 438/7 and 7-2). H.S. was funded by a
structural grant of the BMBF to Neuroimage Nord (grant nr. 01GO 0511).
We greatly appreciate the patients for participating in this study. We
would like to thank Dirk Dressler, Department of Neurology at the
Hannover Medical School, Alexander Munchau, Department of Neurology at
the University of Hamburg, Lars Timmermann, Department of Neurology,
University of Cologne and Markus Butz, Department of Neurology,
University of Dusseldorf for referring patients to us.
NR 64
TC 51
Z9 51
U1 2
U2 9
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD JAN 1
PY 2011
VL 54
IS 1
BP 32
EP 41
DI 10.1016/j.neuroimage.2010.08.013
PG 10
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 675IY
UT WOS:000283825000006
PM 20708692
ER
PT J
AU Zhang, XC
Salmeron, BJ
Ross, TJ
Geng, XJ
Yang, YH
Stein, EA
AF Zhang, Xiaochu
Salmeron, Betty Jo
Ross, Thomas J.
Geng, Xiujuan
Yang, Yihong
Stein, Elliot A.
TI Factors underlying prefrontal and insula structural alterations in
smokers
SO NEUROIMAGE
LA English
DT Article
ID WHITE-MATTER INTEGRITY; NICOTINE DEPENDENCE; CIGARETTE-SMOKING; SPATIAL
STATISTICS; COCAINE DEPENDENCE; GRAY-MATTER; MIDDLE-AGE; MR-IMAGES;
IN-VIVO; DIFFUSION
AB Based upon previous reports of alterations in white matter integrity and gray matter density in smokers, we examined these markers in a large, well-matched sample of smokers and non-smokers. We further investigated the effect of heavy cigarette exposure by using pack-years and the effects of two relatively stable, highly heritable traits in smokers (Fagerstrom Test of Nicotine Dependence (FIND), a measure of severity of nicotine dependence and Toronto Alexithymia Scale (TAS-20), a stable personality trait related to smoking). Forty-eight nicotine-dependent subjects and 48 matched controls were included in the analyses, with smokers also subdivided into high/low dependence and high/low pack-years smokers. White matter integrity (fractional anisotropy (FA)) and gray matter density (voxel-based morphometry (VBM)) were measured and compared across groups. Gray matter density was lower in left prefrontal cortex (PFC) in high pack-years smokers and was inversely related to pack-years. In contrast, left insular cortex gray matter density was higher in smokers and associated with TAS-20 total score and with difficulty-identifying-feelings factor. Further, the most highly dependent smokers showed lower prefrontal FA, which was negatively correlated with FEND. There was no correlation between pack-years and FIND in our smoker population. These data suggest chronic tobacco use is correlated with prefrontal gray matter damage, while differences in insula gray matter and PFC white matter appear to reflect stable and heritable differences between smokers and non-smokers. Published by Elsevier Inc.
C1 [Zhang, Xiaochu; Salmeron, Betty Jo; Ross, Thomas J.; Geng, Xiujuan; Yang, Yihong; Stein, Elliot A.] Natl Inst Drug Abuse, Neuroimaging Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Stein, EA (reprint author), Natl Inst Drug Abuse, Neuroimaging Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
EM estein@mail.nih.gov
RI Ross, Thomas/B-7469-2008; Geng, Xiujuan/I-3852-2012; 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 This research was supported by the Intramural Research Program of the
National Institute on Drug Abuse, NIH. We thank Kimberly Modo and
Loretta Spurgeon for their assistance in the conduct of the study and
Mary Pfeiffer for editing assistance.
NR 63
TC 82
Z9 85
U1 2
U2 13
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD JAN 1
PY 2011
VL 54
IS 1
BP 42
EP 48
DI 10.1016/j.neuroimage.2010.08.008
PG 7
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 675IY
UT WOS:000283825000007
PM 20699124
ER
PT J
AU Zhang, XC
Salmeron, BJ
Ross, TJ
Gu, H
Geng, XJ
Yang, YH
Stein, EA
AF Zhang, Xiaochu
Salmeron, Betty Jo
Ross, Thomas J.
Gu, Hong
Geng, Xiujuan
Yang, Yihong
Stein, Elliot A.
TI Anatomical differences and network characteristics underlying smoking
cue reactivity
SO NEUROIMAGE
LA English
DT Article
DE Smoking cue; Anatomical; ASL; DTI; VBM; Resting state functional
connectivity
ID CEREBRAL-BLOOD-FLOW; STRIATUM/NUCLEUS ACCUMBENS ACTIVATION; STATE
FUNCTIONAL CONNECTIVITY; COGNITIVE CONTROL; NICOTINE DEPENDENCE;
CIGARETTE-SMOKING; PROCESSING MODEL; NEURAL ACTIVITY; BRAIN ACTIVITY;
COCAINE
AB A distributed network of brain regions is linked to drug-related cue responding. However, the relationships between smoking cue-induced phasic activity and possible underlying differences in brain structure, tonic neuronal activity and connectivity between these brain areas are as yet unclear. Twenty-two smokers and 22 controls viewed smoking-related and neutral pictures during a functional arterial spin labeling scanning session. T1, resting functional, and diffusion tensor imaging data were also collected. Six brain areas, dorsal lateral prefrontal cortex (dIPFC), dorsal medial prefrontal cortex (dmPFC), dorsal anterior cingulate cortex/cingulate cortex, rostral anterior cingulate cortex (rACC), occipital cortex, and insula/operculum, showed significant smoking cue-elicited activity in smokers when compared with controls and were subjected to secondary analysis for resting state functional connectivity (rsFC). structural, and tonic neuronal activity. rsFC strength between rACC and dIPFC was positively correlated with the cue-elicited activity in dIPFC. Similarly, rsFC strength between dIPFC and dmPFC was positively correlated with the cue-elicited activity in dmPFC while rsFC strength between dmPFC and insula/operculum was negatively correlated with the cue-elicited activity in both dmPFC and insula/operculum, suggesting these brain circuits may facilitate the response to the salient smoking cues. Further, the gray matter density in dIPFC was decreased in smokers and correlated with cue-elicited activity in the same brain area, suggesting a neurobiological mechanism for the impaired cognitive control associated with drug use. Taken together, these results begin to address the underlying neurobiology of smoking cue salience, and may speak to novel treatment strategies and targets for therapeutic interventions. Published by Elsevier Inc.
C1 [Zhang, Xiaochu; Salmeron, Betty Jo; Ross, Thomas J.; Gu, Hong; Geng, Xiujuan; Yang, Yihong; Stein, Elliot A.] Natl Inst Drug Abuse, Neuroimaging Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Stein, EA (reprint author), Natl Inst Drug Abuse, Neuroimaging Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
EM estein@mail.nih.gov
RI Ross, Thomas/B-7469-2008; Geng, Xiujuan/I-3852-2012; 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 This research was supported by the Intramural Research Program of the
National Institute on Drug Abuse, NIH. We thank Kimberly Modo and
Loretta Spurgeon for their assistance in the conduct of some of the
studies reported herein and Mary Pfeiffer for editing assistance. The
authors reported no financial interests or potential conflicts of
interest.
NR 74
TC 43
Z9 48
U1 0
U2 10
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD JAN 1
PY 2011
VL 54
IS 1
BP 131
EP 141
DI 10.1016/j.neuroimage.2010.07.063
PG 11
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 675IY
UT WOS:000283825000016
PM 20688176
ER
PT J
AU Strobel, A
Zimmermann, J
Schmitz, A
Reuter, M
Lis, S
Windmann, S
Kirsch, P
AF Strobel, Alexander
Zimmermann, Jan
Schmitz, Anja
Reuter, Martin
Lis, Stefanie
Windmann, Sabine
Kirsch, Peter
TI Beyond revenge: Neural and genetic bases of altruistic punishment
SO NEUROIMAGE
LA English
DT Article
DE Altruistic punishment; Functional magnetic resonance imaging; Nucleus
accumbens; Nucleus caudatus; Catechol-O-methyltransferase; Polymorphism
ID ECONOMIC DECISION-MAKING; PREFRONTAL CORTEX; ULTIMATUM GAME; REWARD;
DOPAMINE; BRAIN; NEUROBIOLOGY; POLYMORPHISM; SENSITIVITY; RECIPROCITY
AB It is still debated how altruistic punishment as one form of strong reciprocity has established during evolution and which motives may underlie such behavior. Recent neuroscientific evidence on the activation of brain reward regions during altruistic punishment in two-person one-shot exchange games suggests satisfaction through the punishment of norm violations as one underlying motive. In order to address this issue in more detail, we used fMRI during a one-shot economic exchange game that warrants strong reciprocity by introducing a third party punishment condition wherein revenge is unlikely to play a role. We report here that indeed, reward regions such as the nucleus accumbens showed punishment-related activation. Moreover, we provide preliminary evidence that genetic variation of dopamine turnover impacts similarly on punishment-related nucleus accumbens activation during both first person and third party punishment. The overall pattern of results suggests a common cognitive-affective-motivational network as the driving force for altruistic punishment, with only quantitative differences between first person and third party perspectives. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Strobel, Alexander] Tech Univ Dresden, Dept Psychol, D-01062 Dresden, Germany.
[Strobel, Alexander; Zimmermann, Jan; Windmann, Sabine] Goethe Univ Frankfurt, Inst Psychol, D-6000 Frankfurt, Germany.
[Zimmermann, Jan] Maastricht Univ, Dept Cognit Neurosci, Maastricht, Netherlands.
[Schmitz, Anja] Univ Giessen, Inst Psychol, D-35390 Giessen, Germany.
[Schmitz, Anja] NIMH, NIH, Bethesda, MD 20892 USA.
[Reuter, Martin] Univ Bonn, Inst Psychol, D-5300 Bonn, Germany.
[Lis, Stefanie; Kirsch, Peter] Univ Giessen, Ctr Psychiat, D-35390 Giessen, Germany.
[Kirsch, Peter] Cent Inst Mental Hlth, Dept Clin Psychol, D-68159 Mannheim, Germany.
RP Strobel, A (reprint author), Tech Univ Dresden, Dept Psychol, Mommsenstr 13, D-01062 Dresden, Germany.
EM alex.strobel@gmx.de; peter.kirsch@zi-mannheim.de
RI Strobel, Alexander/I-5026-2015;
OI Strobel, Alexander/0000-0002-9426-5397; Zimmermann,
Jan/0000-0003-3345-6074; Kirsch, Peter/0000-0002-0817-1248; Lis,
Stefanie/0000-0002-8051-2756
NR 42
TC 56
Z9 57
U1 11
U2 73
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD JAN 1
PY 2011
VL 54
IS 1
BP 671
EP 680
DI 10.1016/j.neuroimage.2010.07.051
PG 10
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 675IY
UT WOS:000283825000069
PM 20673803
ER
PT J
AU Kateb, B
Chiu, K
Black, KL
Yamamoto, V
Khalsa, B
Ljubimova, JY
Ding, H
Patil, R
Portilla-Arias, JA
Modo, M
Moore, DF
Farahani, K
Okun, MS
Prakash, N
Neman, J
Ahdoot, D
Grundfest, W
Nikzad, S
Heiss, JD
AF Kateb, Babak
Chiu, Katherine
Black, Keith L.
Yamamoto, Vicky
Khalsa, Bhavraj
Ljubimova, Julia Y.
Ding, Hui
Patil, Rameshwar
Portilla-Arias, Jose Antonio
Modo, Mike
Moore, David F.
Farahani, Keyvan
Okun, Michael S.
Prakash, Neal
Neman, Josh
Ahdoot, Daniel
Grundfest, Warren
Nikzad, Shouleh
Heiss, John D.
TI Nanoplatforms for constructing new approaches to cancer treatment,
imaging, and drug delivery: What should be the policy?
SO NEUROIMAGE
LA English
DT Article
DE Nanoplatforms; Nanotechnology; Image-guided therapy; Nanomedicine;
Nanoneurosurgery; Nanostructures; Contrast agents; Nanoparticles;
Nanotechnology policy; Nano-radiology; Nano-neuroscience; Nano-neurology
ID NEPHROGENIC SYSTEMIC FIBROSIS; IRON-OXIDE NANOPARTICLES; FUNCTIONALIZED
CARBON NANOTUBES; MAGNETIC-RESONANCE TRACKING; BLOOD-BRAIN-BARRIER; MRI
CONTRAST AGENTS; PLURONIC((R)) BLOCK-COPOLYMERS; SEMICONDUCTOR QUANTUM
DOTS; VX-2 RABBIT TUMORS; SIALYL-LEWIS-X
AB Nanotechnology is the design and assembly of submicroscopic devices called nanoparticles, which are 1-100 nm in diameter. Nanomedicine is the application of nanotechnology for the diagnosis and treatment of human disease. Disease-specific receptors on the surface of cells provide useful targets for nanoparticles. Because nanoparticles can be engineered from components that (1) recognize disease at the cellular level, (2) are visible on imaging studies, and (3) deliver therapeutic compounds, nanotechnology is well suited for the diagnosis and treatment of a variety of diseases. Nanotechnology will enable earlier detection and treatment of diseases that are best treated in their initial stages, such as cancer. Advances in nanotechnology will also spur the discovery of new methods for delivery of therapeutic compounds, including genes and proteins, to diseased tissue. A myriad of nanostructured drugs with effective site-targeting can be developed by combining a diverse selection of targeting, diagnostic, and therapeutic components. Incorporating immune target specificity with nanostructures introduces a new type of treatment modality, nano-immunochemotherapy, for patients with cancer. In this review, we will discuss the development and potential applications of nanoscale platforms in medical diagnosis and treatment. To impact the care of patients with neurological diseases, advances in nanotechnology will require accelerated translation to the fields of brain mapping, CNS imaging, and nanoneurosurgery. Advances in nanoplatform, nano-imaging, and nano-drug delivery will drive the future development of nanomedicine, personalized medicine, and targeted therapy. We believe that the formation of a science, technology, medicine law-healthcare policy (STML) hub/center, which encourages collaboration among universities, medical centers, US government, industry, patient advocacy groups, charitable foundations, and philanthropists, could significantly facilitate such advancements and contribute to the translation of nanotechnology across medical disciplines. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Kateb, Babak; Moore, David F.; Okun, Michael S.; Prakash, Neal; Grundfest, Warren; Nikzad, Shouleh; Heiss, John D.] IBMISPS, W Hollywood, CA 90046 USA.
[Kateb, Babak; Ahdoot, Daniel; Grundfest, Warren; Nikzad, Shouleh] Brain Mapping Fdn, W Hollywood, CA 90046 USA.
[Kateb, Babak] Univ So Calif, Viterbi Sch Engn, Los Angeles, CA 90089 USA.
[Kateb, Babak; Yamamoto, Vicky; Nikzad, Shouleh] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
[Kateb, Babak; Black, Keith L.; Ljubimova, Julia Y.; Ding, Hui; Patil, Rameshwar; Portilla-Arias, Jose Antonio] Cedars Sinai Med Ctr, Maxine Dunitz Neurosurg Inst, Los Angeles, CA 90048 USA.
[Chiu, Katherine; Khalsa, Bhavraj] Univ Calif Irvine, Sch Med, Irvine, CA 92697 USA.
[Moore, David F.] Walter Reed Army Med Ctr, DVBIC, Washington, DC 20307 USA.
[Modo, Mike] Kings Coll London, London WC2R 2LS, England.
[Neman, Josh; Grundfest, Warren] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Okun, Michael S.] Univ Florida, Movement Disorders Ctr, Dept Neurol, Gainesville, FL 32610 USA.
[Okun, Michael S.] Univ Florida, Movement Disorders Ctr, Dept Neurosurg, Gainesville, FL 32610 USA.
[Prakash, Neal] Univ Hawaii, John A Burns Sch Med, Manoa, HI 96813 USA.
[Farahani, Keyvan] NCI, Bethesda, MD 20892 USA.
[Heiss, John D.] NINDS, Bethesda, MD 20824 USA.
[Nikzad, Shouleh] CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA.
RP Kateb, B (reprint author), IBMISPS, 8159 Santa Monica Blvd,Suite 200, W Hollywood, CA 90046 USA.
EM Bkateb@ibmisps.org
RI Modo, Michel/E-5170-2012; Farahani, Keyvan/G-9069-2012; PORTILLA-ARIAS,
JOSE/C-3223-2008;
OI PORTILLA-ARIAS, JOSE/0000-0003-1105-1842; Khalsa,
Bhavraj/0000-0003-0915-931X; Okun, Michael/0000-0002-6247-9358; Heiss,
John/0000-0002-3890-0165; Modo, Michel/0000-0003-4436-735X
FU NIH/NCI [R01 CA123495]; NIBIB [1 P20 EB007076-01]
FX We would like to specially thank Dr. Eggehard Holler for his
contribution to the paper. Our thanks and appreciation to Dr. Nakissa
Sadrieh for her permission to include the table on FDA-approved drugs in
the nanometer scale. We would also like to acknowledge Julia Ljubimova
and Mike Modo's grant support from the NIH/NCI R01 CA123495 grant and
NIBIB (Quantum Grant-1 P20 EB007076-01), respectively. Dr. Modo's NIBIB
Quantum Grant is directed towards tissue engineering and brain research
(PEG-based hydrogels, etc.). We acknowledge Dr. Behnam Badie for his
editorial contributions and Rohit Majumdar and Adrian Au for their time
and help in conducting the literature search. This work is also made
possible through a generous contribution of the Brain Mapping
Foundation. The contents of this paper are solely the responsibility of
the authors and represent the official position of the IBMISP Society.
The contents do not represent the official views of NINDS/NIH and
NCI/NIH.
NR 237
TC 65
Z9 67
U1 10
U2 77
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD JAN
PY 2011
VL 54
SU 1
BP S106
EP S124
DI 10.1016/j.neuroimage.2010.01.105
PG 19
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 813ZF
UT WOS:000294408600016
PM 20149882
ER
PT J
AU Mays, J
Butts, CL
AF Mays, Jacqueline
Butts, Cherie L.
TI Intercommunication between the Neuroendocrine and Immune Systems: Focus
on Myasthenia Gravis
SO NEUROIMMUNOMODULATION
LA English
DT Article
DE Autoimmunity; Thymoma; Acetylcholine receptor; Steroid hormones; Immune
system
ID RECEPTOR ALPHA-SUBUNIT; ACETYLCHOLINE-RECEPTOR; NEUROMUSCULAR-JUNCTION;
CLASS-II; T-CELLS; ANTIBODIES; ESTROGEN; EXPRESSION; PREGNANCY; THYMOMA
AB Crosstalk exists between the nervous, endocrine, and immune systems, and perturbations in these interactions have been associated with disease. This includes production of neuroendocrine factors that alter immune system activity and increase susceptibility to or severity of immune-related conditions, such as myasthenia gravis (MG) - a T-cell-dependent, B-cell-mediated autoimmune disorder. MG results from impairment of transmission to the neuromuscular junction and involves the thymus - especially in early-onset disease, but the exact mechanism by which the thymus impacts disease is unclear. MG afflicts millions of individuals worldwide each year, and both men and women can develop symptoms. However, prevalence and age of onset differs between men and women. Women exhibit higher incidence and earlier age of onset compared to men, and disease fluctuates during pregnancy. This suggests that sex hormones play a role in influencing disease outcome. In this review, we will consider what is known about the manifestation of MG, theories on how different forms of MG are influenced or alleviated by steroid hormones, current treatment options, and what measures could be important to consider in the future. Copyright (C) 2011 S. Karger AG, Basel
C1 [Butts, Cherie L.] US FDA, Immunol Lab, Div Therapeut Prot, Off Biotechnol Prod,Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA.
[Mays, Jacqueline] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Butts, CL (reprint author), US FDA, Immunol Lab, Div Therapeut Prot, Off Biotechnol Prod,Ctr Drug Evaluat & Res, 8800 Rockville Pike,HFD 122,Bldg 29A,Room 3B19, Bethesda, MD 20892 USA.
EM cherie.butts@fda.hhs.gov
NR 57
TC 3
Z9 3
U1 0
U2 1
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 1021-7401
J9 NEUROIMMUNOMODULAT
JI Neuroimmunomodulation
PY 2011
VL 18
IS 5
BP 320
EP 327
DI 10.1159/000329491
PG 8
WC Endocrinology & Metabolism; Immunology; Neurosciences
SC Endocrinology & Metabolism; Immunology; Neurosciences & Neurology
GA 823XT
UT WOS:000295162000008
PM 21952684
ER
PT B
AU Montes, J
Kaufmann, P
AF Montes, Jacqueline
Kaufmann, Petra
BE Tawil, RN
Venance, S
TI Spinal Muscular Atrophy
SO NEUROMUSCULAR DISORDERS
SE Neurology in Practice
LA English
DT Article; Book Chapter
ID CONSENSUS STATEMENT; CLASSIFICATION; SMA; SURVIVAL; STANDARD; TYPE-1;
MOUSE; CARE
C1 [Montes, Jacqueline] Columbia Univ, Dept Neurol, SMA Clin Res Ctr, New York, NY 10027 USA.
[Kaufmann, Petra] NINDS, NIH, Bethesda, MD 20892 USA.
RP Montes, J (reprint author), Columbia Univ, Dept Neurol, SMA Clin Res Ctr, New York, NY 10027 USA.
NR 15
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER, WEST SUSSEX PO19 8SQ, ENGLAND
BN 978-1-119-97330-0; 978-0-470-65456-9
J9 NEUROL PRACT
PY 2011
BP 229
EP 235
D2 10.1002/9781119973331
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA BA7AV
UT WOS:000337348200032
ER
PT J
AU Alushin, GM
Jane, D
Mayer, ML
AF Alushin, Gregory M.
Jane, David
Mayer, Mark L.
TI Binding site and ligand flexibility revealed by high resolution crystal
structures of GluK1 competitive antagonists
SO NEUROPHARMACOLOGY
LA English
DT Article
DE Glutamate receptors; Crystal structure; Conformational flexibility;
Halogen bond
ID KAINATE RECEPTOR ANTAGONIST; PARTIAL AGONIST ACTION; GLUR2 AMPA
RECEPTOR; GLUTAMATE-RECEPTOR; PHARMACOLOGICAL CHARACTERIZATION; NMDA
RECEPTORS; HALOGEN BONDS; DOMOIC ACID; CORE DIMER; IN-VIVO
AB The availability of crystal structures for the ligand binding domains of ionotropic glutamate receptors, combined with their key role in synaptic function in the normal and diseased brain, offers a unique selection of targets for pharmaceutical research compared to other drug targets for which the atomic structure of the ligand binding site is not known. Currently only a few antagonist structures have been solved, and these reveal ligand specific conformational changes that hinder rational drug design. Here we report high resolution crystal structures for three kainate receptor GluK1 antagonist complexes which reveal new and unexpected modes of binding, highlighting the continued need for experimentally determined receptor-ligand complexes. Published by Elsevier Ltd.
C1 [Alushin, Gregory M.; Mayer, Mark L.] NICHD, Lab Cellular & Mol Neurophysiol, Porter Neurosci Res Ctr, NIH,DHHS, Bethesda, MD 20892 USA.
[Jane, David] Univ Bristol, Dept Pharmacol, MRC Ctr Synapt Plast, Bristol BS8 1TD, Avon, England.
RP Mayer, ML (reprint author), NICHD, Lab Cellular & Mol Neurophysiol, Porter Neurosci Res Ctr, NIH,DHHS, Bldg 35,Room 3B 1002,35 Lincoln Dr, Bethesda, MD 20892 USA.
EM mlm@helix.nih.gov
RI Mayer, Mark/H-5500-2013
FU U.S. Department of Energy, Office of Science, Office of Basic Energy
Sciences [W-31-109-Eng-38]; NICHD, NIH, DHHS; BBSRC
FX GMA was a postbac IRTA fellow of the NIH. Synchrotron diffraction data
was collected at Southeast Regional Collaborative Access Team (SER-CAT)
22-ID beamline at the Advanced Photon Source, Argonne National
Laboratory. Supporting institutions may be found at
www.ser-cat.org/members.html. Use of the Advanced Photon Source was
supported by the U.S. Department of Energy, Office of Science, Office of
Basic Energy Sciences, under Contract No. W-31-109-Eng-38. This work was
supported by the intramural research program of NICHD, NIH, DHHS. Work
leading to the synthesis of UBP315 and UBP318 was supported by the
BBSRC. We thank Dr. David Bleakman for the gift of LY466195 and Dr.
Jinjin Zhang for comments on the manuscript.
NR 52
TC 14
Z9 14
U1 2
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3908
J9 NEUROPHARMACOLOGY
JI Neuropharmacology
PD JAN
PY 2011
VL 60
IS 1
BP 126
EP 134
DI 10.1016/j.neuropharm.2010.06.002
PG 9
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 703PA
UT WOS:000285989500015
PM 20558186
ER
PT J
AU Bisgaard, H
Larsen, MAB
Mazier, S
Beuming, T
Newman, AH
Weinstein, H
Shi, L
Loland, CJ
Gether, U
AF Bisgaard, Heidi
Larsen, M. Andreas B.
Mazier, Sonia
Beuming, Thijs
Newman, Amy Hauck
Weinstein, Hare
Shi, Lei
Loland, Claus J.
Gether, Ulrik
TI The binding sites for benztropines and dopamine in the dopamine
transporter overlap
SO NEUROPHARMACOLOGY
LA English
DT Article
DE Neurotransmitter:sodium symporters; Monoamine transporters; Dopamine
transporter; Cocaine; Molecular modeling; Mutagenesis
ID HUMAN SEROTONIN TRANSPORTER; NEUROTRANSMITTER TRANSPORTERS; UPTAKE
INHIBITORS; POPULATION PHARMACOKINETICS; MONOAMINE TRANSPORTERS;
CONFORMATIONAL-CHANGES; BRAIN DISTRIBUTION; BACTERIAL HOMOLOG; COCAINE
BINDING; ANALOGS
AB Analogs of benztropines (BZTs) are potent inhibitors of the dopamine transporter (DAT) but are less effective than cocaine as behavioral stimulants. As a result, there have been efforts to evaluate these compounds as leads for potential medication for cocaine addiction. Here we use computational modeling together with site-directed mutagenesis to characterize the binding site for BZTs in DAT. Docking into molecular models based on the structure of the bacterial homolog LeuT supported a BZT binding site that overlaps with the substrate-binding pocket. In agreement, mutations of residues within the pocket, including(2) Val152(3.46) to Ala or Ile, Ser422(8.60) to Ala and Asn157(3.51) to Cys or Ala, resulted in decreased affinity for BZT and the analog JHW007, as assessed in [(3)H]dopamine uptake inhibition assays and/or [(3)H] CFT competition binding assay. A putative polar interaction of one of the phenyl ring fluorine substituents in JHW007 with Asn157(3.51) was used as a criterion for determining likely binding poses and establish a structural context for the mutagenesis findings. The analysis positioned the other fluorine-substituted phenyl ring of JHW007 in close proximity to Ala479(10.51)/Ala480(10.52) in transmembrane segment (TM) 10. The lack of such an interaction for BZT led to a more tilted orientation, as compared to JHW007, bringing one of the phenyl rings even closer to Ala479(10.51)/Ala480(10.52). Mutation of Ala479(10.51) and Ala480(10.52) to valines supported these predictions with a larger decrease in the affinity for Bit than for JHW007. Summarized, our data suggest that BZTs display a classical competitive binding mode with binding sites overlapping those of cocaine and dopamine. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Gether, Ulrik] Univ Copenhagen, Panum Inst, Dept Neurosci & Pharmacol,Mol Neuropharmacol Lab, Mol Neuropharmacol Grp,Fac Hlth Sci, DK-2200 Copenhagen N, Denmark.
[Mazier, Sonia; Weinstein, Hare; Shi, Lei] Cornell Univ, Weill Cornell Med Coll, Dept Physiol & Biophys, New York, NY 10065 USA.
[Beuming, Thijs] Schrodinger Inc, New York, NY 10036 USA.
[Weinstein, Hare; Shi, Lei] Cornell Univ, Weill Cornell Med Coll, HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsau, New York, NY 10065 USA.
[Newman, Amy Hauck] NIDA, Med Chem Sect, Medicat Discovery Res Branch, Intramural Res Program,Dept Hlth & Human Serv,NIH, Baltimore, MD 21224 USA.
RP Gether, U (reprint author), Univ Copenhagen, Panum Inst, Dept Neurosci & Pharmacol,Mol Neuropharmacol Lab, Mol Neuropharmacol Grp,Fac Hlth Sci, Bldg 18-6,Blegdamsvej 3, DK-2200 Copenhagen N, Denmark.
EM gether@sund.ku.dk
RI Loland, Claus/E-5975-2014; Bisgaard, Hans/N-4761-2016;
OI Loland, Claus/0000-0002-1773-1446; Bisgaard, Hans/0000-0003-4131-7592;
Gether, Ulrik/0000-0002-0020-3807
FU National Institute of Health [P01 DA12408, R00 DA023694]; NIDA; Danish
Health Science Research Council; Lundbeck Foundation; Novo Nordisk
Foundation; Maersk Foundation
FX We thank Pia Elsman for technical assistance and Jianjing Cao for
synthesizing the BZT analogs used in this study. The work was supported
in part by the National Institute of Health Grants P01 DA12408 (HW and
UG), R00 DA023694 (LS), the NIDA-Intramural Research Program (A.H.N),
the Danish Health Science Research Council (CJL and UG), the Lundbeck
Foundation (CJL and UG), the Novo Nordisk Foundation (CJL and UG), and
the Maersk Foundation (CJL).
NR 49
TC 27
Z9 27
U1 0
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3908
J9 NEUROPHARMACOLOGY
JI Neuropharmacology
PD JAN
PY 2011
VL 60
IS 1
BP 182
EP 190
DI 10.1016/j.neuropharm.2010.08.021
PG 9
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 703PA
UT WOS:000285989500020
PM 20816875
ER
PT J
AU Petrides, G
Tobias, KG
Kellner, CH
Rudorfer, MV
AF Petrides, Georgios
Tobias, Kristen G.
Kellner, Charles H.
Rudorfer, Matthew V.
TI Continuation and Maintenance Electroconvulsive Therapy for Mood
Disorders: Review of the Literature
SO NEUROPSYCHOBIOLOGY
LA English
DT Review
DE Electroconvulsive therapy; Continuation electroconvulsive therapy;
Maintenance electroconvulsive therapy; Mood disorders; Review
ID RANDOMIZED CONTROLLED-TRIAL; RESISTANT BIPOLAR DISORDER; LIFE PSYCHOTIC
DEPRESSION; RELAPSE PREVENTION; CATATONIC SCHIZOPHRENIA;
PARKINSONS-DISEASE; CONVULSIVE THERAPY; MAJOR DEPRESSION; REFRACTORY
MANIA; ELDERLY-PATIENTS
AB Background: Electroconvulsive therapy (ECT) is a highly effective treatment for mood disorders. Continuation ECT (C-ECT) and maintenance ECT (M-ECT) are required for many patients suffering from severe and recurrent forms of mood disorders. This is a review of the literature regarding C- and M-ECT. Methods: We conducted a computerized search using the words continuation ECT, maintenance ECT, depression, mania, bipolar disorder and mood disorders. We report on all articles published in the English language from 1998 to 2009. Results: We identified 32 reports. There were 24 case reports and retrospective reviews on 284 patients. Two of these reports included comparison groups, and 1 had a prospective follow-up in a subset of subjects. There were 6 prospective naturalistic studies and 2 randomized controlled trials. Conclusions: C-ECT and M-ECT are valuable treatment modalities to prevent relapse and recurrence of mood disorders in patients who have responded to an index course of ECT. C-ECT and M-ECT are underused and insufficiently studied despite positive clinical experience of more than 70 years. Studies which are currently under way should allow more definitive recommendations regarding the choice, frequency and duration of C-ECT and M-ECT following acute ECT. Copyright (C) 2011 S. Karger AG, Basel
C1 [Petrides, Georgios] N Shore LIJ Hlth Syst, Div Res, Zucker Hillside Hosp, Glen Oaks, NY 11004 USA.
[Tobias, Kristen G.; Kellner, Charles H.] Mt Sinai Sch Med, New York, NY USA.
[Rudorfer, Matthew V.] NIMH, Bethesda, MD 20892 USA.
RP Petrides, G (reprint author), N Shore LIJ Hlth Syst, Div Res, Zucker Hillside Hosp, 7559 263rd St, Glen Oaks, NY 11004 USA.
EM petrides@lij.edu
OI Kellner, Charles/0000-0001-9663-3571
NR 76
TC 30
Z9 31
U1 3
U2 12
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0302-282X
EI 1423-0224
J9 NEUROPSYCHOBIOLOGY
JI Neuropsychobiology
PY 2011
VL 64
IS 3
BP 129
EP 140
DI 10.1159/000328943
PG 12
WC Neurosciences; Psychiatry; Psychology
SC Neurosciences & Neurology; Psychiatry; Psychology
GA 815UM
UT WOS:000294555300002
PM 21811083
ER
PT J
AU Djamshidian, A
O'Sullivan, SS
Doherty, K
Lees, AJ
Averbeck, BB
AF Djamshidian, Atbin
O'Sullivan, Sean S.
Doherty, Karen
Lees, Andrew J.
Averbeck, Bruno B.
TI Altruistic punishment in patients with Parkinson's disease with and
without impulsive behaviour
SO NEUROPSYCHOLOGIA
LA English
DT Article
DE Parkinson's disease; Altruistic punishment; Impulsive compulsive
behaviour; Dopaminergic medication
ID DOPAMINE DYSREGULATION SYNDROME; CONTROL DISORDERS; COMPULSIVE USE;
NEURAL BASIS; REWARD; PERSONALITY; ASSOCIATION; PREVALENCE; MEDICATION;
MECHANISMS
AB Punishing violators of social norms when there is personal cost is known as altruistic punishment. We tested patients with Parkinson's disease (PD) with and without impulsive-compulsive behaviours (ICBs) and matched control subjects, on and off their regular dopamine replacement therapy on a task, in which the patients decided whether or not to invest a sum of money with a trustee. The sum was then quadrupled and the trustee could decide whether or not to return a portion of the investment. Participants could punish the trustee after they were informed of the trustee's decision. We found that PD patients without ICBs on or off medication punished more often than controls, whereas PD patients with ICBs punished more than controls on medication, but similar to controls off medication. These results suggest a role for dopamine in altruistic punishment decisions in PD patients with impulsive compulsive behaviour. Published by Elsevier Ltd.
C1 [Averbeck, Bruno B.] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
[Averbeck, Bruno B.] UCL, Inst Neurol, Sobell Dept Motor Neurosci & Movement Disorders, London WC1N 3BG, England.
[Djamshidian, Atbin; O'Sullivan, Sean S.; Doherty, Karen; Lees, Andrew J.] Univ London, Dept Mol Neurosci, London, England.
[Djamshidian, Atbin; O'Sullivan, Sean S.; Doherty, Karen; Lees, Andrew J.] Univ London, Reta Lila Weston Inst Neurol Studies, London, England.
RP Averbeck, BB (reprint author), NIMH, Neuropsychol Lab, NIH, Bldg 49 Room 1B80,49 Convent Dr,MSC 4415, Bethesda, MD 20892 USA.
EM bruno.averbeck@nih.gov
RI O'Sullivan, Sean/C-9333-2012; Lees, Andrew/A-6605-2009;
OI O'Sullivan, Sean/0000-0002-0583-7956; Djamshidian,
Atbin/0000-0001-7174-6000
FU PSP Association; Weston Trust-The Reta Lila Howard Foundation; Wellcome;
National Institute of Mental Health; Department of Health's NIHR
Biomedical Research Centres
FX All authors reported no conflict of interest in the content of this
paper. AJL receives honoraria from Novartis, Teva, Meda, Boehringer
Ingelheim, GSK, Ipsen, Lundbeck, Allergan, Orion, grants from the PSP
Association, Weston Trust-The Reta Lila Howard Foundation and
consultancies from Genus. SOS has received honoraria from Britannia
Pharmaceuticals. BBA receives research support from Wellcome, and the
Intramural research program of the National Institute of Mental Health.;
We are grateful to Prof. Peter Brown for critically reading our
manuscript and to Dr. Constantinos Kallis for his statistical advice. We
like to thank all patients and their partners who participated on this
study. This work was undertaken at UCLH/UCL who received a proportion of
funding from the Department of Health's NIHR Biomedical Research Centres
funding scheme.
NR 37
TC 8
Z9 8
U1 1
U2 8
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3932
J9 NEUROPSYCHOLOGIA
JI Neuropsychologia
PD JAN
PY 2011
VL 49
IS 1
BP 103
EP 107
DI 10.1016/j.neuropsychologia.2010.10.012
PG 5
WC Behavioral Sciences; Neurosciences; Psychology, Experimental
SC Behavioral Sciences; Neurosciences & Neurology; Psychology
GA 712WS
UT WOS:000286697600011
PM 20965203
ER
PT J
AU Tanaka, S
Sandrini, M
Cohen, LG
AF Tanaka, Satoshi
Sandrini, Marco
Cohen, Leonardo G.
TI Modulation of motor learning and memory formation by non-invasive
cortical stimulation of the primary motor cortex
SO NEUROPSYCHOLOGICAL REHABILITATION
LA English
DT Article
DE Motor learning; Memory; Adaptation; TMS; tDCS; Rehabilitation; Stroke
ID TRANSCRANIAL MAGNETIC STIMULATION; USE-DEPENDENT PLASTICITY; INDUCED
MOVEMENT THERAPY; CHRONIC STROKE PATIENTS; PARADOXICAL FUNCTIONAL
FACILITATION; ALTERNATING-CURRENT STIMULATION; CONSTRAINT-INDUCED
THERAPY; PLACEBO-CONTROLLED TRIAL; UPPER EXTREMITY FUNCTION; THETA-BURST
STIMULATION
AB Transcranial magnetic (TMS) and direct current (tDCS) stimulation are non-invasive brain stimulation techniques that allow researchers to purposefully modulate cortical excitability in focal areas of the brain. Recent work has provided preclinical evidence indicating that TMS and tDCS can facilitate motor performance, motor memory formation, and motor skill learning in healthy subjects and possibly in patients with brain lesions. Although the optimal stimulation parameters to accomplish these goals remain to be determined, and controlled multicentre clinical studies are lacking, these findings suggest that cortical stimulation techniques could become in the future adjuvant strategies in the rehabilitation of motor deficits. The aim of this article is to critically review these findings and to discuss future directions regarding the possibility of combining these techniques with other interventions in neurorehabilitation.
C1 [Sandrini, Marco; Cohen, Leonardo G.] NINDS, Human Cort Physiol & Stroke Neurorehabil Sect, NIH, Bethesda, MD 20892 USA.
[Tanaka, Satoshi] Natl Inst Physiol Sci, Div Cerebral Integrat, Okazaki, Aichi 444, Japan.
[Sandrini, Marco] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA.
RP Cohen, LG (reprint author), NINDS, Human Cort Physiol & Stroke Neurorehabil Sect, NIH, 10 Ctr Dr Bethesda, Bethesda, MD 20892 USA.
EM cohenl@ninds.nih.gov
RI Sandrini, Marco/J-2276-2014
OI Sandrini, Marco/0000-0002-1664-5722
FU NINDS, NIH; KAKENHI [22700442]; Department of Defense in the Center for
Neuroscience and Regenerative Medicine
FX This work was supported by the Intramural Research Program of the NINDS,
NIH and grants from the Grants-in-Aid for Scientific Research (KAKENHI)
to ST (22700442) and by funding from Department of Defense in the Center
for Neuroscience and Regenerative Medicine to MS. Satoshi Tanaka and
Marco Sandrini contributed equally to this work.
NR 198
TC 23
Z9 23
U1 4
U2 24
PU PSYCHOLOGY PRESS
PI HOVE
PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND
SN 0960-2011
J9 NEUROPSYCHOL REHABIL
JI Neuropsychol. Rehabil.
PY 2011
VL 21
IS 5
SI SI
BP 650
EP 675
DI 10.1080/09602011.2011.605589
PG 26
WC Neurosciences; Psychology
SC Neurosciences & Neurology; Psychology
GA 885OS
UT WOS:000299789100006
PM 21942897
ER
PT J
AU Hohman, TJ
Beason-Held, LL
Lamar, M
Resnick, SM
AF Hohman, Timothy J.
Beason-Held, Lori L.
Lamar, Melissa
Resnick, Susan M.
TI Subjective Cognitive Complaints and Longitudinal Changes in Memory and
Brain Function
SO NEUROPSYCHOLOGY
LA English
DT Article
DE aging; cerebral blood flow; memory; cognitive failures
ID ALZHEIMERS-DISEASE; OLDER-PEOPLE; TEST-PERFORMANCE; VERBAL MEMORY;
SELF-REPORT; IMPAIRMENT; DEMENTIA; DECLINE; AGE; ADULTS
AB Objective: Subjective cognitive complaints are often used in the diagnosis of memory and other cognitive impairment. This study examined whether cognitive complaints are associated with longitudinal changes in cognition and cross-sectional differences in regional brain function during memory performance in 98 participants with a mean age of 75. Method: The Cognitive Failures Questionnaire (CFQ) assessed cognitive complaints and mixed effects regression models were used to determine whether mean CFQ scores predicted rates of change in cognitive function over a period of 11.5 years. Results: Higher CFQ scores, reflecting increased subjective complaints, were associated with steeper rates of decline in immediate and delayed recall on the California Verbal Learning Test. Voxel-based regression analysis was used to determine the cross-sectional relationship between CFQ scores and regional cerebral blood flow measured by PET during a resting condition and during verbal and figural memory tasks. Higher levels of cognitive complaints were associated with increased activity in insular, lingual and cerebellar areas during memory tasks. Conclusions: These findings offer some support for the validity of subjective cognitive complaints as markers of age related changes in memory and brain activity.
C1 [Hohman, Timothy J.] NIA, LPC, Biomed Res Ctr, Baltimore, MD 21224 USA.
[Hohman, Timothy J.] American Univ, Dept Psychol, Washington, DC 20016 USA.
[Lamar, Melissa] Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA.
RP Hohman, TJ (reprint author), NIA, LPC, Biomed Res Ctr, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA.
EM hohmantj@mail.nih.gov
OI Hohman, Timothy/0000-0002-3377-7014
FU NIH, National Institute on Aging
FX This research was supported in part by the Intramural Research Program
of the NIH, National Institute on Aging. We are grateful to the BLSA
participants and neuroimaging staff for their dedication to these
studies and the staff of the Johns Hopkins PET facility for their
assistance.
NR 39
TC 48
Z9 49
U1 2
U2 13
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0894-4105
J9 NEUROPSYCHOLOGY
JI Neuropsychology
PD JAN
PY 2011
VL 25
IS 1
BP 125
EP 130
DI 10.1037/a0020859
PG 6
WC Psychology, Clinical; Neurosciences; Psychology
SC Psychology; Neurosciences & Neurology
GA 711AQ
UT WOS:000286558500013
PM 20919769
ER
PT J
AU Swanson, J
Baler, RD
Volkow, ND
AF Swanson, James
Baler, Ruben D.
Volkow, Nora D.
TI Understanding the Effects of Stimulant Medications on Cognition in
Individuals with Attention-Deficit Hyperactivity Disorder: A Decade of
Progress
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Review
DE methylphenidate; amphetamine; dopamine; prefrontal cortex; executive
function; cognitive enhancement
ID FUNCTIONAL MAGNETIC-RESONANCE; STRIATAL DOPAMINE TRANSPORTERS;
PERFORMANCE-TEST PERFORMANCE; MEDIAL PREFRONTAL CORTEX; BOLD SIGNAL
FLUCTUATIONS; SPATIAL WORKING-MEMORY; PARENT-CHILD DYADS; LONG-TERM
OUTCOMES; EVENT-RELATED FMRI; DRUG-NAIVE BOYS
AB The use of stimulant drugs for the treatment of children with attention-deficit hyperactivity disorder (ADHD) is one of the most widespread pharmacological interventions in child psychiatry and behavioral pediatrics. This treatment is well grounded on controlled studies showing efficacy of low oral doses of methylphenidate and amphetamine in reducing the behavioral symptoms of the disorder as reported by parents and teachers, both for the cognitive (inattention and impulsivity) and noncognitive (hyperactivity) domains. Our main aim is to review the objectively measured cognitive effects that accompany the subjectively assessed clinical responses to stimulant medications. Recently, methods from the cognitive neurosciences have been used to provide information about brain processes that underlie the cognitive deficits of ADHD and the cognitive effects of stimulant medications. We will review some key findings from the recent literature, and then offer interpretations of the progress that has been made over the past decade in understanding the cognitive effects of stimulant medication on individuals with ADHD. Neuropsychopharmacology Reviews (2011) 36, 207-226; doi: 10.1038/npp.2010.160; published online 29 September 2010
C1 [Baler, Ruben D.; Volkow, Nora D.] NIDA, NIH, Bethesda, MD 20892 USA.
[Swanson, James] Univ Calif Irvine, Dept Pediat, Irvine, CA 92717 USA.
RP Volkow, ND (reprint author), NIDA, NIH, Bethesda, MD 20892 USA.
EM nvolkow@nida.nih.gov
NR 189
TC 101
Z9 103
U1 12
U2 65
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD JAN
PY 2011
VL 36
IS 1
BP 207
EP 226
DI 10.1038/npp.2010.160
PG 20
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 688TR
UT WOS:000284877300011
PM 20881946
ER
PT J
AU Goldstein, RZ
Volkow, ND
AF Goldstein, Rita Z.
Volkow, Nora D.
TI Oral Methylphenidate Normalizes Cingulate Activity and Decreases
Impulsivity in Cocaine Addiction During an Emotionally Salient Cognitive
Task
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Editorial Material
ID ANTERIOR CINGULATE; CORTEX
C1 [Goldstein, Rita Z.] Brookhaven Natl Lab, Ctr Translat Neuroimaging, Dept Med Res, Upton, NY 11973 USA.
[Volkow, Nora D.] NIAAA, Rockville, MD 20852 USA.
[Volkow, Nora D.] Natl Inst Drug Abuse, Bethesda, MD USA.
RP Goldstein, RZ (reprint author), Brookhaven Natl Lab, Ctr Translat Neuroimaging, Dept Med Res, Upton, NY 11973 USA.
EM rgoldstein@bnl.gov
FU NCRR NIH HHS [5-M01-RR-10710, M01 RR010710]; NIDA NIH HHS [R01DA023579,
R01 DA023579]
NR 6
TC 15
Z9 15
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD JAN
PY 2011
VL 36
IS 1
BP 366
EP 367
DI 10.1038/npp.2010.145
PG 3
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 688TR
UT WOS:000284877300030
PM 21116260
ER
PT J
AU Nair, SG
Navarre, BM
Cifani, C
Pickens, CL
Bossert, JM
Shaham, Y
AF Nair, Sunila G.
Navarre, Brittany M.
Cifani, Carlo
Pickens, Charles L.
Bossert, Jennifer M.
Shaham, Yavin
TI Role of Dorsal Medial Prefrontal Cortex Dopamine D1-Family Receptors in
Relapse to High-Fat Food Seeking Induced by the Anxiogenic Drug
Yohimbine
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE diet; medial prefrontal cortex; reinstatement; relapse; stress;
yohimbine
ID CORTICOTROPIN-RELEASING-FACTOR; CUE-INDUCED REINSTATEMENT;
COCAINE-INDUCED REINSTATEMENT; CONDITIONED PLACE PREFERENCE;
NUCLEUS-ACCUMBENS CORE; EXCESSIVE SUGAR INTAKE; STRESS-INDUCED RELAPSE;
C-FOS; 5-HT2C RECEPTORS; HEROIN-SEEKING
AB In humans, relapse to maladaptive eating habits during dieting is often provoked by stress. In rats, the anxiogenic drug yohimbine, which causes stress-like responses in both humans and nonhumans, reinstates food seeking in a relapse model. In this study, we examined the role of medial prefrontal cortex (mPFC) dopamine D1-family receptors, previously implicated in stress-induced reinstatement of drug seeking, in yohimbine-induced reinstatement of food seeking. We trained food-restricted rats to lever press for 35% high-fat pellets every other day (9-15 sessions, 3 h each); pellet delivery was accompanied by a discrete tone-light cue. We then extinguished operant responding for 10-16 days by removing the pellets. Subsequently, we examined the effect of yohimbine (2 mg/kg, i.p.) on reinstatement of food seeking and Fos (a neuronal activity marker) induction in mPFC. We then examined the effect of systemic injections of the D1-family receptor antagonist SCH23390 (10 mu g/kg, s.c.) on yohimbine-induced reinstatement and Fos induction, and that of mPFC SCH23390 (0.5 and 1.0 mu g/side) injections on this reinstatement. Yohimbine-induced reinstatement was associated with strong Fos induction in the dorsal mPFC and with weaker Fos induction in the ventral mPFC. Systemic SCH23390 injections blocked both yohimbine-induced reinstatement and mPFC Fos induction. Dorsal, but not ventral, mPFC injections of SCH23390 decreased yohimbine-induced reinstatement of food seeking. In addition, dorsal mPFC SCH23390 injections decreased pellet-priming-induced reinstatement, but had no effect on ongoing high-fat pellet self-administration or discrete-cue-induced reinstatement. Results indicate a critical role of dorsal mPFC dopamine D1-family receptors in stress-induced relapse to palatable food seeking, as well as relapse induced by acute re-exposure to food taste, texture, and smell. Neuropsychopharmacology (2011) 36, 497-510; doi:10.1038/npp.2010.181; published online 20 October 2010
C1 [Nair, Sunila G.; Navarre, Brittany M.; Cifani, Carlo; Pickens, Charles L.; Bossert, Jennifer M.; Shaham, Yavin] NIDA, Behav Neurosci Branch, IRP, NIH,DHHS, Baltimore, MD 21224 USA.
RP Shaham, Y (reprint author), NIDA, Behav Neurosci Branch, IRP, NIH,DHHS, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA.
EM Yshaham@intra.nida.nih.gov
RI shaham, yavin/G-1306-2014;
OI Cifani, Carlo/0000-0001-6180-828X
FU National Institute on Drug Abuse
FX The work was supported by the Intramural Research Program of the
National Institute on Drug Abuse. We thank Drs Bruce Hope and Eisuke
Koya for their help with the immunohistochemical assays and image
analyses, and Dr Kenner Rice for synthesizing M100907 for experiment 4.
NR 109
TC 45
Z9 46
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD JAN
PY 2011
VL 36
IS 2
BP 497
EP 510
DI 10.1038/npp.2010.181
PG 14
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 694JE
UT WOS:000285292200011
PM 20962767
ER
PT J
AU Sandrini, M
Umilta, C
Rusconi, E
AF Sandrini, Marco
Umilta, Carlo
Rusconi, Elena
TI The use of transcranial magnetic stimulation in cognitive neuroscience:
A new synthesis of methodological issues
SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
LA English
DT Review
DE TMS; rTMS; Theta burst; State-dependency; fMRI; EEG; Safety; Number
processing
ID HUMAN MOTOR CORTEX; POSTERIOR PARIETAL CORTEX; CONCURRENT TMS-FMRI;
MENTAL NUMBER LINE; DORSOLATERAL PREFRONTAL CORTEX; VENTRAL PREMOTOR
CORTEX; PARADOXICAL FUNCTIONAL FACILITATION; VISUAL CORTICAL
EXCITABILITY; THETA-BURST STIMULATION; ANTERIOR TEMPORAL-LOBES
AB Transcranial magnetic stimulation (TMS) has become a mainstay of cognitive neuroscience, thus facing new challenges due to its widespread application on behaviorally silent areas. In this review we will summarize the main technical and methodological considerations that are necessary when using TMS in cognitive neuroscience, based on a corpus of studies and technical improvements that has become available in most recent years. Although TMS has been applied only relatively recently on a large scale to the study of higher functions, a range of protocols that elucidate how this technique can be used to investigate a variety of issues is already available, such as single pulse, paired pulse, dual-site, repetitive and theta burst TMS. Finally, we will touch on recent promising approaches that provide powerful new insights about causal interactions among brain regions (i.e., TMS with other neuroimaging techniques) and will enable researchers to enhance the functional resolution of TMS (i.e., state-dependent TMS). We will end by briefly summarizing and discussing the implications of the newest safety guidelines. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Sandrini, Marco] NINDS, Human Cort Physiol & Stroke Neurorehabil Sect, NIH, Bethesda, MD 20892 USA.
[Sandrini, Marco] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Henry M Jackson Fdn, Rockville, MD 20852 USA.
[Umilta, Carlo] Univ Padua, Dept Gen Psychol, I-35131 Padua, Italy.
[Rusconi, Elena] UCL, Dept Secur & Crime Sci, London WC1E 7HN, England.
[Rusconi, Elena] Univ Trent, Ctr Mind Brain Sci CIMeC, Funct Neuroimaging Labs, I-38060 Mattarello, TN, Italy.
RP Sandrini, M (reprint author), NINDS, Human Cort Physiol & Stroke Neurorehabil Sect, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM marco.sandrini@nih.gov
RI Sandrini, Marco/J-2276-2014
OI Sandrini, Marco/0000-0002-1664-5722
NR 252
TC 93
Z9 93
U1 8
U2 63
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0149-7634
J9 NEUROSCI BIOBEHAV R
JI Neurosci. Biobehav. Rev.
PD JAN
PY 2011
VL 35
IS 3
BP 516
EP 536
DI 10.1016/j.neubiorev.2010.06.005
PG 21
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 712CJ
UT WOS:000286639900013
PM 20599555
ER
PT J
AU Crawley, JN
AF Crawley, Jacqueline N.
TI Behavioral phenotyping strategies for genetic mouse models of autism
SO NEUROSCIENCE RESEARCH
LA English
DT Meeting Abstract
C1 [Crawley, Jacqueline N.] NIMH, LBN, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0168-0102
J9 NEUROSCI RES
JI Neurosci. Res.
PY 2011
VL 71
SU S
BP E38
EP E38
DI 10.1016/j.neures.2011.07.167
PG 1
WC Neurosciences
SC Neurosciences & Neurology
GA 998DT
UT WOS:000308218100164
ER
PT J
AU Hayashi, T
AF Hayashi, Teruo
TI The molecular function of the novel chaperone sigma-1 receptor
SO NEUROSCIENCE RESEARCH
LA English
DT Meeting Abstract
C1 [Hayashi, Teruo] NIDA, Cellular Stress Signaling Unit, Cellular Pathobiol Sect, IRP,NIH, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0168-0102
J9 NEUROSCI RES
JI Neurosci. Res.
PY 2011
VL 71
SU S
BP E34
EP E34
DI 10.1016/j.neures.2011.07.146
PG 1
WC Neurosciences
SC Neurosciences & Neurology
GA 998DT
UT WOS:000308218100143
ER
PT J
AU Mishra, S
Hoon, M
AF Mishra, Santosh
Hoon, Mark
TI TRPV1 lineage neurons and their functional role in thermal nociception
SO NEUROSCIENCE RESEARCH
LA English
DT Meeting Abstract
C1 [Mishra, Santosh; Hoon, Mark] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0168-0102
J9 NEUROSCI RES
JI Neurosci. Res.
PY 2011
VL 71
SU S
BP E80
EP E80
DI 10.1016/j.neures.2011.07.341
PG 1
WC Neurosciences
SC Neurosciences & Neurology
GA 998DT
UT WOS:000308218100339
ER
PT J
AU Shukla, V
Pant, HC
AF Shukla, Varsha
Pant, Harish C.
TI Hyperphosphorylation of tau by deregulated Cdk5 (Cdk5/p25) activity is
inhibited by its truncated activator (p35)
SO NEUROSCIENCE RESEARCH
LA English
DT Meeting Abstract
C1 [Shukla, Varsha; Pant, Harish C.] NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0168-0102
J9 NEUROSCI RES
JI Neurosci. Res.
PY 2011
VL 71
SU S
BP E186
EP E186
DI 10.1016/j.neures.2011.07.804
PG 1
WC Neurosciences
SC Neurosciences & Neurology
GA 998DT
UT WOS:000308218101049
ER
PT J
AU Masdeu, JC
AF Masdeu, Joseph C.
TI Neuroimaging in Psychiatric Disorders
SO NEUROTHERAPEUTICS
LA English
DT Article
DE Magnetic resonance imaging; Positron emission tomography; Single photon
emission tomography; Depression; Schizophrenia; Drug development
ID POSITRON-EMISSION-TOMOGRAPHY; EXTRASTRIATAL DOPAMINE-D-2 RECEPTORS;
SEROTONIN TRANSPORTER OCCUPANCY; MAJOR DEPRESSIVE DISORDER;
ALZHEIMERS-DISEASE; FRONTOTEMPORAL DEMENTIA; SCHIZOPHRENIC SUBJECTS;
PREFRONTAL CORTEX; DRUG DISCOVERY; BASE-LINE
AB In psychiatry, neuroimaging facilitates the diagnosis of psychiatric disorders and the development of new medications. It is used to detect structural lesions causing psychosis and to differentiate depression from neurodegenerative disorders or brain tumors. Functional neuroimaging, mostly in the form of molecular neuroimaging with positron emission tomography or single photon emission tomography, facilitates the identification of therapeutic targets, the determination of the dose of a new drug needed to occupy its target in the brain, and the selection of patients for clinical trials.
C1 NIMH, Sect Integrat Neuroimaging, Intramural Res Program, NIH,CBDS, Bethesda, MD 20892 USA.
RP Masdeu, JC (reprint author), NIMH, Sect Integrat Neuroimaging, Intramural Res Program, NIH,CBDS, 9000 Rockville Pike,Bldg 10,Room 3C111, Bethesda, MD 20892 USA.
EM masdeu@nih.gov
FU National Institute of Mental Health, National Institutes of Health, USA
FX This work was supported by the Intramural Research Program of the
National Institute of Mental Health, National Institutes of Health, USA.
NR 58
TC 7
Z9 8
U1 2
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1933-7213
EI 1878-7479
J9 NEUROTHERAPEUTICS
JI Neurotherapeutics
PD JAN
PY 2011
VL 8
IS 1
BP 93
EP 102
DI 10.1007/s13311-010-0006-0
PG 10
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 750RU
UT WOS:000289566500011
PM 21274689
ER
PT J
AU Zhang, W
Phillips, K
Wielgus, AR
Liu, J
Albertini, A
Zucca, FA
Faust, R
Qian, SY
Miller, DS
Chignell, CF
Wilson, B
Jackson-Lewis, V
Przedborski, S
Joset, D
Loike, J
Hong, JS
Sulzer, D
Zecca, L
AF Zhang, Wei
Phillips, Kester
Wielgus, Albert R.
Liu, Jie
Albertini, Alberto
Zucca, Fabio A.
Faust, Rudolph
Qian, Steven Y.
Miller, David S.
Chignell, Colin F.
Wilson, Belinda
Jackson-Lewis, Vernice
Przedborski, Serge
Joset, Danielle
Loike, John
Hong, Jau-Shyong
Sulzer, David
Zecca, Luigi
TI Neuromelanin Activates Microglia and Induces Degeneration of
Dopaminergic Neurons: Implications for Progression of Parkinson's
Disease
SO NEUROTOXICITY RESEARCH
LA English
DT Article
DE Substantia nigra; Neuroinflammation; Microglia; Neurodegenerative
diseases
ID SUBSTANTIA-NIGRA; ALZHEIMERS-DISEASE; NEUROTOXICITY; MODEL;
NEURODEGENERATION; MECHANISMS; FEATURES; BRAIN; IRON
AB In Parkinson's disease (PD), there is a progressive loss of neuromelanin (NM)-containing dopamine neurons in substantia nigra (SN) which is associated with microgliosis and presence of extracellular NM. Herein, we have investigated the interplay between microglia and human NM on the degeneration of SN dopaminergic neurons. Although NM particles are phagocytized and degraded by microglia within minutes in vitro, extracellular NM particles induce microglial activation and ensuing production of superoxide, nitric oxide, hydrogen peroxide (H(2)O(2)), and pro-inflammatory factors. Furthermore, NM produces, in a microglia-depended manner, neurodegeneration in primary ventral midbrain cultures. Neurodegeneration was effectively attenuated with microglia derived from mice deficient in macrophage antigen complex-1, a microglial integrin receptor involved in the initiation of phagocytosis. Neuronal loss was also attenuated with microglia derived from mice deficient in phagocytic oxidase, a subunit of NADPH oxidase, that is responsible for superoxide and H(2)O(2) production, or apocynin, an NADPH oxidase inhibitor. In vivo, NM injected into rat SN produces microgliosis and a loss of tyrosine hydroxylase neurons. Thus, these results show that extracellular NM can activate microglia, which in turn may induce dopaminergic neurodegeneration in PD. Our study may have far-reaching implications, both pathogenic and therapeutic.
C1 [Albertini, Alberto; Zucca, Fabio A.; Zecca, Luigi] Italian Natl Res Council, Inst Biomed Technol, I-20090 Milan, Italy.
[Jackson-Lewis, Vernice] Columbia Univ, Dept Neurol, New York, NY 10032 USA.
[Przedborski, Serge] Columbia Univ, Dept Neurol Pathol & Cell Biol, New York, NY 10032 USA.
[Joset, Danielle; Loike, John] Columbia Univ, Dept Physiol & Cellular Biophys, New York, NY 10032 USA.
[Zhang, Wei] Beijing Tiantan Hosp, Dept Neurol, Beijing 100050, Peoples R China.
[Phillips, Kester; Faust, Rudolph; Sulzer, David] Columbia Univ, Dept Psychiat Neurol & Pharmacol, New York, NY 10032 USA.
[Wielgus, Albert R.; Qian, Steven Y.; Miller, David S.; Chignell, Colin F.; Wilson, Belinda; Hong, Jau-Shyong] NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA.
[Liu, Jie] NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI,NIH, Res Triangle Pk, NC 27709 USA.
RP Zecca, L (reprint author), Italian Natl Res Council, Inst Biomed Technol, Via Cervi 93, I-20090 Milan, Italy.
EM luigi.zecca@itb.cnr.it
RI Zucca, Fabio/O-4368-2015;
OI Zucca, Fabio/0000-0003-1230-1129; albertini, alberto/0000-0002-7989-649X
FU Michael J. Fox Foundation (New York, NY, USA); MIUR-FIRB (Italy)
[RBNE03PX83_002]; National Parkinson Foundation-Parkinson Disease's
Foundation (Miami, FL; and New York, NY, USA); NINDS [NS062180,
NS11766-27A1, NS38370-09]; NIA [AG21617-01A1]; US DoD [DAMD 17-03-1-02];
Parkinson's Disease Foundation (NY, USA); MDA/WOW; Hartman Foundation;
NIH/NIEHS
FX The authors thank the Legal Medicine Section, Department of Human
Morphology and Biomedical Sciences, University of Milano, and the
authors also thank Ms. Chiara Bellei for skilful assistance. K.P., A.A.,
F.A.Z., R.F., D.S., and L.Z. were supported with the grant of Michael J.
Fox Foundation (New York, NY, USA), MIUR-FIRB Project RBNE03PX83_002 on
Protein Folding and Aggregation: Metal and Biomolecules in Protein
Conformational Diseases (Italy) and Joint Research Grant of National
Parkinson Foundation-Parkinson Disease's Foundation (Miami, FL; and New
York, NY, USA). S.P. is supported by the NINDS Grants NS062180,
NS11766-27A1, and NS38370-09, the NIA Grant AG21617-01A1, the US DoD
Contract DAMD 17-03-1-02, as well as the Parkinson's Disease Foundation
(NY, USA), the MDA/WOW, and the Hartman Foundation. This research was
supported in part by the Intramural Research Program of the NIH/NIEHS.
NR 31
TC 69
Z9 73
U1 1
U2 22
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1029-8428
J9 NEUROTOX RES
JI Neurotox. Res.
PD JAN
PY 2011
VL 19
IS 1
BP 63
EP 72
DI 10.1007/s12640-009-9140-z
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 721QB
UT WOS:000287368600007
PM 19957214
ER
PT J
AU Eugenin, EA
King, JE
Hazleton, JE
Major, EO
Bennett, MVL
Zukin, RS
Berman, JW
AF Eugenin, E. A.
King, J. E.
Hazleton, J. E.
Major, E. O.
Bennett, M. V. L.
Zukin, R. S.
Berman, Joan W.
TI Differences in NMDA Receptor Expression During Human Development
Determine the Response of Neurons to HIV-Tat-mediated Neurotoxicity
SO NEUROTOXICITY RESEARCH
LA English
DT Article
DE HIV-1; NeuroAIDS; Glutamate; NMDA; Dementia; HAND
ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN-FETAL BRAIN;
CENTRAL-NERVOUS-SYSTEM; AMINO-ACID RECEPTORS; D-ASPARTATE RECEPTOR;
NF-KAPPA-B; NEUROLOGICAL DISEASE; PROGENITOR CELLS; PROTEINS TAT; JC
VIRUS
AB HIV infection of the CNS can result in neurologic dysfunction in a significant number of infected individuals. NeuroAIDS is characterized by neuronal injury and loss, yet there is no evidence of HIV infection in neurons. Thus, neuronal damage and dropout are likely due to indirect effects of HIV infection of other CNS cells, through elaboration of inflammatory factors and neurotoxic viral proteins, including the viral transactivating protein tat. We and others demonstrated that tat induces apoptosis in differentiated mature human neurons. We now demonstrate that the high level of tat toxicity observed in human neurons involves specific developmental stages that correlate with N-Methyl-D-Aspartate receptor (NMDAR) expression, and that tat toxicity is also dependent upon the species being analyzed. Our results indicate that tat treatment of primary cultures of differentiated human neurons with significant amounts of NMDAR expression induces extensive apoptosis. In contrast, tat treatment induces only low levels of apoptosis in primary cultures of immature human neurons with low or minimal expression of NMDAR. In addition, tat treatment has minimal effect on rat hippocampal neurons in culture, despite their high expression of NMDAR. We propose that this difference may be due to low expression of the NR2A subunit. These findings are important for an understanding of the many differences among tissue culture systems and species used to study HIV-tat-mediated toxicity.
C1 [Eugenin, E. A.; King, J. E.; Hazleton, J. E.; Berman, Joan W.] Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA.
[Berman, Joan W.] Albert Einstein Coll Med, Dept Microbiol Immunol, Bronx, NY 10461 USA.
[Bennett, M. V. L.; Zukin, R. S.] Albert Einstein Coll Med, Dept Neurosci, Bronx, NY 10461 USA.
[Major, E. O.] NINDS, NIH, Mol Med & Virol Sect, Bethesda, MD 20892 USA.
RP Berman, JW (reprint author), Albert Einstein Coll Med, Dept Pathol, Forchheimer 727,1300 Morris Pk Ave, Bronx, NY 10461 USA.
EM joan.berman@einstein.yu.edu
FU National Institutes of Mental Health [MH070297, MH075679, MH083497,
MH076679]; National Institute of Neurological Disorders and Stroke
[NS055363, NS045287, NS020752]; MSTP [5 T32 GM007288]; HIV AIDS and
Opportunistic Infection Institutional Training Grant [T32 AI-007501];
NIH Centers for AIDS Research at the Albert Einstein College of Medicine
[(CFAR) AI-051519]
FX We are grateful to Dr. Brad Poulos and The Human Fetal Tissue Repository
at the AECOM. This work was supported by the National Institutes of
Mental Health Grants MH070297, MH075679, and MH083497 to J. W. B. and by
a RO1 grant from the National Institute of Mental Health (MH076679) to
E.A.E., National Institute of Neurological Disorders and Stroke
(NS055363 and NS045287 to M.V.L.B. and NS020752 to R.S.Z.), MSTP
Training Grant, 5 T32 GM007288 (to JEK and JEH), and from the HIV AIDS
and Opportunistic Infection Institutional Training Grant, T32 AI-007501
(to JEH). We thank the NIH Centers for AIDS Research Grant (CFAR)
AI-051519 at the Albert Einstein College of Medicine.
NR 48
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U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1029-8428
J9 NEUROTOX RES
JI Neurotox. Res.
PD JAN
PY 2011
VL 19
IS 1
BP 138
EP 148
DI 10.1007/s12640-010-9150-x
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 721QB
UT WOS:000287368600015
PM 20094923
ER
PT J
AU Khalsa, JH
AF Khalsa, Jag H.
TI Preface to understanding developmental consequences of prenatal drug
exposure: Biological and environmental effects and their interactions
SO NEUROTOXICOLOGY AND TERATOLOGY
LA English
DT Editorial Material
DE Drug abuse; Pregnancy
C1 Natl Inst Drug Abuse, Med Consequences Branch, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, Bethesda, MD 20892 USA.
RP Khalsa, JH (reprint author), Natl Inst Drug Abuse, Med Consequences Branch, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, 6001 Execut Blvd,Room 4137,MSC 9551, Bethesda, MD 20892 USA.
EM jkhalsa@nida.nih.gov
FU Intramural NIH HHS [Z99 DA999999]
NR 8
TC 0
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U1 1
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0892-0362
J9 NEUROTOXICOL TERATOL
JI Neurotoxicol. Teratol.
PD JAN-FEB
PY 2011
VL 33
IS 1
SI SI
BP 3
EP 4
DI 10.1016/j.ntt.2010.10.009
PG 2
WC Neurosciences; Toxicology
SC Neurosciences & Neurology; Toxicology
GA 724XN
UT WOS:000287609800001
PM 21056101
ER
PT J
AU Bada, HS
Bann, CM
Bauer, CR
Shankaran, S
Lester, B
LaGasse, L
Hammond, J
Whitaker, T
Das, A
Tan, S
Higgins, R
AF Bada, Henrietta S.
Bann, Carla M.
Bauer, Charles R.
Shankaran, Seetha
Lester, Barry
LaGasse, Linda
Hammond, Jane
Whitaker, Toni
Das, Abhik
Tan, Sylvia
Higgins, Rosemary
TI Preadolescent behavior problems after prenatal cocaine exposure:
Relationship between teacher and caretaker ratings (Maternal Lifestyle
Study)
SO NEUROTOXICOLOGY AND TERATOLOGY
LA English
DT Article
DE Prenatal cocaine; Externalizing behavior; Attention problems; Prenatal
opiate; Caretaker depression; Community violence; School behavior
ID SCHOOL-AGE-CHILDREN; IN-UTERO; COMMUNITY VIOLENCE; DRUG EXPOSURE;
INFANTS; OUTCOMES; MOTHERS; MODEL; BRAIN; RISK
AB Background: We previously reported an association between prenatal cocaine exposure (PCE) and childhood behavior problems as observed by the parent or caretaker. However, these behavior problems may not manifest in a structured environment, such as a school setting.
Objective: We determined whether there is an association between PCE and school behavior problems and whether ratings of behavior problems from the teacher differ from those noted by the parent or caretaker.
Methods: The Maternal Lifestyle Study, a multicenter study, enrolled 1388 children with and without PCE at one month of age for longitudinal assessment Teachers masked to prenatal drug exposure status completed the Teacher Report Form (TRF/6-18) when children were 7, 9, and 11 years old. We also administered the Child Behavior Checklist-parent report (CBCL) to the parent/caretaker at same ages and then at 13 years. We performed latent growth curve modeling to determine whether high PCE will predict externalizing, internalizing, total behavior, and attention problems at 7 years of age and whether changes in problems' scores over time differ between those exposed and non-exposed from both teacher and parent report. Besides levels of PCE as predictors, we controlled for the following covariates, namely: site, child characteristics (gender and other prenatal drug exposures), family level influences (maternal age, depression and psychological symptomatology, continuing drug use, exposure to domestic violence, home environment and socioeconomic status), and community level factors (neighborhood and community violence).
Results: The mean behavior problem T scores from the teacher report were significantly higher than ratings by the parent or caretaker. Latent growth curve modeling revealed a significant relationship between intercepts of problem T scores from teacher and parent ratings; i.e., children that were rated poorly by teachers were also rated poorly by their parent/caretaker or vice versa. After controlling for covariates, we found high PCE to be a significant predictor of higher externalizing behavior problem T scores from both parent and teacher report at 7 years (p = 0.034 and p = 0.021, respectively) in comparison to non-PCE children. These differences in scores from either teacher or caregiver were stable through subsequent years or did not change significantly over time. Boys had higher T scores than girls on internalizing and total problems by caretaker report; they also had significantly higher T scores for internalizing, total, and attention problems by teacher ratings; the difference was marginally significant for externalizing behavior (p = 0.070). Caretaker postnatal use of tobacco, depression, and community violence were significant predictors of all behavior problems rated by parent/caretaker, while lower scores on the home environment predicted all behavior outcomes by the teacher report.
Conclusions: Children with high PCE are likely to manifest externalizing behavior problems; their behavior problem scores at 7 years from either report of teacher or parent remained higher than scores of non-exposed children on subsequent years. Screening and identification of behavior problems at earlier ages could make possible initiation of intervention, while considering the likely effects of other confounders. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Bada, Henrietta S.] Univ Kentucky, Albert B Chandler Med Ctr, Dept Pediat, Lexington, KY 40536 USA.
[Bann, Carla M.; Hammond, Jane; Das, Abhik; Tan, Sylvia] RTI Int, Res Triangle Pk, NC 27709 USA.
[Bauer, Charles R.] Univ Miami, Sch Med, Dept Pediat, Miami, FL 33136 USA.
[Shankaran, Seetha] Wayne State Univ, Sch Med, Dept Pediat, Detroit, MI 48201 USA.
[Lester, Barry; LaGasse, Linda] Brown Univ, Sch Med, Dept Pediat, Providence, RI 02905 USA.
[Whitaker, Toni] Univ Tennessee HSC, Dept Pediat, Memphis, TN 38163 USA.
[Higgins, Rosemary] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD 20847 USA.
RP Bada, HS (reprint author), Univ Kentucky, Albert B Chandler Med Ctr, Dept Pediat, 800 Rose St,Room MS 477, Lexington, KY 40536 USA.
EM hbada2@uky.edu
FU National Institutes of Health; Eunice Kennedy Shriver National Institute
of Child Health and Human Development (NICHD); National Institute on
Drug Abuse (NIDA); Administration on Children, Youth, and Families;
Center for Substance Abuse and Treatment; NICHD
FX The National Institutes of Health, the Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD), the National
Institute on Drug Abuse (NIDA), the Administration on Children, Youth,
and Families, and the Center for Substance Abuse and Treatment provided
grant support for recruiting subjects into the Maternal Lifestyle Study
in 1993-1995. NIDA and NICHD provided funding to conduct follow-up
examinations in five phases: at 1, 4, 8, 10, 12, 18, 24, and 36 months
corrected age (Phase 1 and Phase II); at 31/2, 4, 41/2, 5, 51/2, 6, and
7 years of age (Phase III); and at 8, 9, 10, and 11 years of age (Phase
IV). NICHD, NIDA, and NIMH provided continuing funding for ages 12, 13,
14, 15, and 16 years (Phase V). The funding agencies provided overall
oversight of study conduct, but all data analyses and interpretation
were completed independent of the funding agencies. We are indebted to
our medical and nursing colleagues and the infants and their parents who
agreed to take part in this study.
NR 69
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PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0892-0362
J9 NEUROTOXICOL TERATOL
JI Neurotoxicol. Teratol.
PD JAN-FEB
PY 2011
VL 33
IS 1
SI SI
BP 78
EP 87
DI 10.1016/j.ntt.2010.06.005
PG 10
WC Neurosciences; Toxicology
SC Neurosciences & Neurology; Toxicology
GA 724XN
UT WOS:000287609800010
PM 20600844
ER
PT J
AU Delaney-Black, V
Chiodo, LM
Hannigan, JH
Greenwald, MK
Janisse, J
Patterson, G
Huestis, MA
Partridge, RT
Ager, J
Sokol, RJ
AF Delaney-Black, Virginia
Chiodo, Lisa M.
Hannigan, John H.
Greenwald, Mark K.
Janisse, James
Patterson, Grace
Huestis, Marilyn A.
Partridge, Robert T.
Ager, Joel
Sokol, Robert J.
TI Prenatal and postnatal cocaine exposure predict teen cocaine use
SO NEUROTOXICOLOGY AND TERATOLOGY
LA English
DT Article
DE Cocaine; Opiates; Marijuana; Self-report; Biologic sample
ID SUBSTANCE-USE INITIATION; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER;
DRUG-USE; ADULT RATS; BEHAVIOR PROBLEMS; CHILD-BEHAVIOR;
RECEPTOR-BINDING; YOUNG ADULTHOOD; MENTAL-HEALTH; CANNABIS USE
AB Preclinical studies have identified alterations in cocaine and alcohol self-administration and behavioral responses to pharmacological challenges in adolescent offspring following prenatal exposure. To date, no published human studies have evaluated the relation between prenatal cocaine exposure and postnatal adolescent cocaine use. Human studies of prenatal cocaine-exposed children have also noted an increase in behaviors previously associated with substance use/abuse in teens and young adults, specifically childhood and teen externalizing behaviors, impulsivity, and attention problems. Despite these findings, human research has not addressed prior prenatal exposure as a potential predictor of teen drug use behavior. The purpose of this study was to evaluate the relations between prenatal cocaine exposure and teen cocaine use in a prospective longitudinal cohort (n = 316) that permitted extensive control for child, parent and community risk factors. Logistic regression analyses and Structural Equation Modeling revealed that both prenatal exposure and postnatal parent/caregiver cocaine use were uniquely related to teen use of cocaine at age 14 years. Teen cocaine use was also directly predicted by teen community violence exposure and caregiver negativity, and was indirectly related to teen community drug exposure. These data provide further evidence of the importance of prenatal exposure, family and community factors in the intergenerational transmission of teen/young adult substance abuse/use. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Delaney-Black, Virginia; Patterson, Grace] Wayne State Univ, Carman & Ann Adams Dept Pediat, Detroit, MI 48201 USA.
[Chiodo, Lisa M.] Wayne State Univ, Coll Nursing, Detroit, MI 48201 USA.
[Hannigan, John H.; Sokol, Robert J.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Hannigan, John H.; Partridge, Robert T.] Wayne State Univ, Dept Psychol, Detroit, MI 48201 USA.
[Hannigan, John H.; Sokol, Robert J.] Wayne State Univ, CS Mott Ctr Human Growth & Dev, Detroit, MI 48201 USA.
[Hannigan, John H.] Wayne State Univ, Merrill Palmer Skillman Inst, Detroit, MI 48201 USA.
[Greenwald, Mark K.] Wayne State Univ, Dept Psychiat & Behav Neurosci, Detroit, MI 48201 USA.
[Janisse, James; Ager, Joel] Wayne State Univ, Dept Family Med & Publ Hlth Sci, Detroit, MI 48201 USA.
[Huestis, Marilyn A.] Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD 21224 USA.
RP Delaney-Black, V (reprint author), Childrens Hosp Michigan, Carmen & Ann Adams Dept Pediat, 3901 Beaubien, Detroit, MI 48201 USA.
EM vdelaney@med.wayne.edu
RI Chiodo, Lisa/G-1427-2015
OI Chiodo, Lisa/0000-0001-7052-3569
FU National Institute of Health [R01-DA08524, R01-DA016373]; National
Institute on Drug Abuse
FX This study was funded in part by grants from the National Institute of
Health (R01-DA08524 and R01-DA016373) to V. Delaney-Black. MA. Huestis
was supported by the National Institute on Drug Abuse Intramural
Research Program. Preliminary reports of some of these findings were
presented to the annual meetings of PAS and ISDP in 2009.
NR 102
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PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0892-0362
J9 NEUROTOXICOL TERATOL
JI Neurotoxicol. Teratol.
PD JAN-FEB
PY 2011
VL 33
IS 1
SI SI
BP 110
EP 119
DI 10.1016/j.ntt.2010.06.011
PG 10
WC Neurosciences; Toxicology
SC Neurosciences & Neurology; Toxicology
GA 724XN
UT WOS:000287609800013
PM 20609384
ER
PT J
AU Wakschlag, LS
Henry, DB
Blair, RJR
Dukic, V
Burns, J
Pickett, KE
AF Wakschlag, Lauren S.
Henry, David B.
Blair, R. James R.
Dukic, Vanja
Burns, James
Pickett, Kate E.
TI Unpacking the association: Individual differences in the relation of
prenatal exposure to cigarettes and disruptive behavior phenotypes
SO NEUROTOXICOLOGY AND TERATOLOGY
LA English
DT Article
DE Prenatal exposure to cigarettes; Disruptive behavior; Parental
responsiveness; Sex differences; Developmental pathways; Maternal
smoking
ID CHILDHOOD PHYSICAL AGGRESSION; SELF-REPORTED MEASURES; MATERNAL SMOKING;
ANTISOCIAL-BEHAVIOR; CONDUCT PROBLEMS; DEVELOPMENTAL PSYCHOPATHOLOGY;
EXTERNALIZING PROBLEMS; PREGNANCY SMOKING; LATE ADOLESCENCE;
BIRTH-WEIGHT
AB Prenatal exposure to cigarettes has been robustly associated with disruptive behavior in diverse samples and across developmental periods. In this paper we aim to elucidate exposure related behavioral phenotypes and developmental pathways by testing: (a) differential associations of exposure and four disruptive behavior dimensional phenotypes: Aggression, Noncompliance, Temper Loss and Low Concern for Others; and (b) moderation of these pathways including sex differences and moderation by parental responsive engagement. Participants were 211 teens and their parents from the East Boston Family Study (EBFS), an adolescent follow-up of a pregnancy cohort over-sampled for exposure. A best estimate serum cotinine corrected score was used to characterize exposure. In multivariate models controlling for parental antisocial behavior, family adversity and secondhand exposure, exposure uniquely predicted Aggression and Noncompliance. Paternal responsiveness moderated exposure effects on disruptive behavior. There were no sex differences in these patterns. Phenotypic findings suggest the possibility of specific neural mechanisms. In conjunction with prior research, protective effects of parental responsiveness occurring as late as adolescence point to the potential benefit of parenting-based prevention efforts to reduce risk to exposed offspring. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Wakschlag, Lauren S.; Burns, James] Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, Chicago, IL 60611 USA.
[Henry, David B.] Univ Illinois, Sch Publ Hlth, Inst Hlth Res & Policy, Chicago, IL USA.
[Blair, R. James R.] NIMH, Mood & Anxiety Program, Bethesda, MD 20892 USA.
[Dukic, Vanja] Univ Chicago, Sch Med, Dept Hlth Studies, Chicago, IL 60637 USA.
[Pickett, Kate E.] Univ York, Dept Hlth Sci, York YO10 5DD, N Yorkshire, England.
[Pickett, Kate E.] Univ York, Hull York Med Sch, York YO10 5DD, N Yorkshire, England.
RP Wakschlag, LS (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, Abbott Hall,Suite 729,710 N Lake Shore Dr, Chicago, IL 60611 USA.
EM lauriew@northwestern.edu
OI Dukic, Vanja/0000-0002-0348-0834
FU Department of Health [CSA/03/07/014]; NIDA NIH HHS [R01 DA023653, R01
DA015223, R01 DA015223-01A1, R01 DA015223-02, R01 DA015223-03, R01
DA015223-04, R01 DA015223-05, R01 DA015223-06, R01 DA023653-01A2, R01
DA023653-02, R01 DA023653-03]
NR 75
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U1 5
U2 11
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0892-0362
J9 NEUROTOXICOL TERATOL
JI Neurotoxicol. Teratol.
PD JAN-FEB
PY 2011
VL 33
IS 1
SI SI
BP 145
EP 154
DI 10.1016/j.ntt.2010.07.002
PG 10
WC Neurosciences; Toxicology
SC Neurosciences & Neurology; Toxicology
GA 724XN
UT WOS:000287609800017
PM 21256429
ER
PT J
AU LaGasse, LL
Wouldes, T
Newman, E
Smith, LM
Shah, RZ
Derauf, C
Huestis, MA
Arria, AM
Della Grotta, S
Wilcox, T
Lester, BM
AF LaGasse, Linda L.
Wouldes, Trecia
Newman, Elana
Smith, Lynne M.
Shah, Rizwan Z.
Derauf, Chris
Huestis, Marilyn A.
Arria, Amelia M.
Della Grotta, Sheri
Wilcox, Tara
Lester, Barry M.
TI Prenatal methamphetamine exposure and neonatal neurobehavioral outcome
in the USA and New Zealand
SO NEUROTOXICOLOGY AND TERATOLOGY
LA English
DT Article
DE Prenatal exposure; Methamphetamine; Neurodevelopment; Meconium
ID UTERO COCAINE EXPOSURE; MATERNAL LIFE-STYLE; IN-UTERO; NEWBORN
NEUROBEHAVIOR; SUBSTANCE EXPOSURE; INFANT DEVELOPMENT; DEVELOPING BRAIN;
PREGNANT-WOMEN; CHILDREN; DOPAMINE
AB Background: Methamphetamine (MA) use among pregnant women is a world-wide problem, but little is known of its impact on exposed infants.
Design: The prospective, controlled longitudinal Infant Development, Environment and Lifestyle (IDEAL) study of prenatal MA exposure from birth to 36 months was conducted in the US and NZ. The US cohort has 183 exposed and 196 comparison infants; the NZ cohort has 85 exposed and 95 comparison infants. Exposure was determined by self-report and meconium assay with alcohol, marijuana, and tobacco exposures present in both groups. The NICU Neurobehavior Scale (NNNS) was administered within 5 days of life. NNNS summary scores were analyzed for exposure including heavy exposure and frequency of use by trimester and dose-response relationship with the amphetamine analyte.
Results: MA exposure was associated with poorer quality of movement, more total stress/abstinence, physiological stress, and CNS stress with more nonoptimal reflexes in NZ but not in the USA. Heavy MA exposure was associated with lower arousal and excitability. First trimester MA use predicted more stress and third trimester use more lethargy and hypotonicity. Dose-response effects were observed between amphetamine concentration in meconium and CNS stress.
Conclusion: Across cultures, prenatal MA exposure was associated with a similar neurobehavioral pattern of under arousal, low tone, poorer quality of movement and increased stress. (C) 2010 Elsevier Inc. All rights reserved.
C1 [LaGasse, Linda L.; Della Grotta, Sheri; Wilcox, Tara; Lester, Barry M.] Brown Univ, Women & Infants Hosp, Warren Alpert Med Sch, Ctr Study Children Risk, Providence, RI USA.
[Wouldes, Trecia] Univ Auckland, Dept Psychol Med, Auckland 1, New Zealand.
[Newman, Elana] Univ Tulsa, Dept Psychol, Tulsa, OK 74104 USA.
[Smith, Lynne M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Smith, Lynne M.] Harbor UCLA Med Ctr, Los Angeles Biomed Inst, Los Angeles, CA USA.
[Shah, Rizwan Z.] Blank Hosp Reg Child Protect Ctr Iowa Hlth, Des Moines, IA USA.
[Derauf, Chris] Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA.
[Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Baltimore, MD USA.
[Arria, Amelia M.] Univ Maryland, Ctr Subst Abuse Res CESAR, College Pk, MD 20742 USA.
RP LaGasse, LL (reprint author), Brown Ctr Study Children Risk, 101 Dudley St, Providence, RI 02905 USA.
EM Linda_Lagasse@brown.edu
OI Arria, Amelia/0000-0002-6360-9265; Wouldes, Trecia/0000-0002-6609-8464
FU National Institute on Drug Abuse [R01DA021757, R01DA014948]; Auckland
Medical Research Foundation; National Center on Research Resources
[M01RR00426, P20RR11091]; National Institutes of Health
FX This study was supported from the National Institute on Drug Abuse (LLL:
R01DA021757; BML: R01DA014948) and in part from the Auckland Medical
Research Foundation (TW), the National Center on Research Resources
(M01RR00426; P20RR11091) and the National Institutes of Health
Intramural Research Program (MAH). We thank Carolyn Ho, Jennie Rodgers,
Jo Cliffe, and Heather Stewart in NZ and Matt Hinckley, Jean Twomey,
Darlene Decesare, Fatima Guerra and Hai Lin in the US for their
assistance on this international collaboration as well as the staff at
the IDEAL US sites.
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PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0892-0362
J9 NEUROTOXICOL TERATOL
JI Neurotoxicol. Teratol.
PD JAN-FEB
PY 2011
VL 33
IS 1
SI SI
BP 166
EP 175
DI 10.1016/j.ntt.2010.06.009
PG 10
WC Neurosciences; Toxicology
SC Neurosciences & Neurology; Toxicology
GA 724XN
UT WOS:000287609800019
PM 20615464
ER
PT J
AU Smith, LM
LaGasse, LL
Derauf, C
Newman, E
Shah, R
Haning, W
Arria, A
Huestis, M
Strauss, A
Della Grotta, S
Dansereau, LM
Lin, H
Lester, BM
AF Smith, Lynne M.
LaGasse, Linda L.
Derauf, Chris
Newman, Elana
Shah, Rizwan
Haning, William
Arria, Amelia
Huestis, Marilyn
Strauss, Arthur
Della Grotta, Sheri
Dansereau, Lynne M.
Lin, Hai
Lester, Barry M.
TI Motor and cognitive outcomes through three years of age in children
exposed to prenatal methamphetamine
SO NEUROTOXICOLOGY AND TERATOLOGY
LA English
DT Article
DE Prenatal exposure; Neurodevelopment; Bayley; Peabody
ID MATERNAL LIFE-STYLE; COCAINE EXPOSURE; IN-UTERO; INFANT DEVELOPMENT;
INTRAUTERINE GROWTH; RAT PUPS; PREGNANCY; AMPHETAMINE; ENVIRONMENT; TERM
AB Background: Methamphetamine (MA) use among pregnant women is an increasing problem in the United States. The impact of prenatal MA exposure on development in childhood is unknown.
Objective: To examine the effects of prenatal MA exposure on motor and cognitive development in children at 1, 2, and 3 years of age.
Design/methods: IDEAL enrolled 412 mother-infant pairs at four sites (Tulsa OK, Des Moines IA, Los Angeles CA, and Honolulu HI). MA subjects (n = 204) were identified by self report or GC/MS confirmation of amphetamine and metabolites in infant meconium. Comparison subjects (n = 208) were matched (race, birth weight, maternal education, and type of insurance), denied amphetamine use, and had a negative meconium screen. Both groups included prenatal alcohol, tobacco and marijuana use, but excluded use of opiates, lysergic acid diethylamide, phencyclidine or cocaine only. The Peabody Developmental Motor Scales (PDMS-2) were administered to the infants at the 1 and 3 year visits. This analysis includes a subsample (n = 350) of the IDEAL study with completed 1 and/or 3 year visits (n = 330 and 281, respectively). At each annual visit we also conducted the Bayley Scales of Infant Development (BSID-II) as a general evaluation of mental and motor development. The BSID-II analysis includes a subsample (n = 356) of the IDEAL study with completed 1, 2, and/or 3 year visits (n = 331, 288, and 278 respectively). GLM analysis conducted on the PDMS-2 and BSID-II examined the effects of MA exposure and heavy MA exposure (>= 3 days of use/week), with and without covariates. Longitudinal analyses were used to examine the effects of MA exposure on changes in motor and cognitive performance over time.
Results: Heavy MA exposure was associated with significantly lower grasping scores than some and no use at 1 year (P = 0.018). In longitudinal analysis, lower grasping scores associated with any MA exposure and heavy exposure persisted to 3 years. There were no effects of MA exposure, including heavy exposure, on the Bayley Mental Development Index (MDI) or Psychomotor Development Index (PDI) at any or across age.
Conclusions: There were no differences in cognition as assessed by the BSID-II between the groups. There was a subtle MA exposure effect on fine motor performance at 1 year with the poorest performance observed in the most heavily exposed children. By 3 years, no differences in fine motor performance were observed. These findings suggest MA exposure has modest motor effects at 1 year that are mostly resolved by 3 years. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Smith, Lynne M.] Harbor UCLA Med Ctr, Los Angeles Biomed Inst, Torrance, CA 90502 USA.
[Smith, Lynne M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[LaGasse, Linda L.; Della Grotta, Sheri; Dansereau, Lynne M.; Lin, Hai; Lester, Barry M.] Brown Univ, Women & Infants Hosp, Warren Alpert Med Sch, Ctr Study Children Risk, Providence, RI USA.
[Derauf, Chris; Haning, William] Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA.
[Newman, Elana] Univ Tulsa, Dept Psychol, Tulsa, OK 74104 USA.
[Shah, Rizwan] Blank Hosp Reg Child Protect Ctr Iowa Hlth, Des Moines, IA USA.
[Arria, Amelia] Univ Maryland, Ctr Subst Abuse Res CESAR, College Pk, MD 20742 USA.
[Huestis, Marilyn] NIDA, Intramural Res Program, NIH, Baltimore, MD USA.
[Strauss, Arthur] Long Beach Mem Med Ctr, Long Beach, CA USA.
RP Smith, LM (reprint author), Harbor UCLA Med Ctr, Los Angeles Biomed Inst, 1124 W Carson St,Box 446, Torrance, CA 90502 USA.
EM smith@labiomed.org
OI Arria, Amelia/0000-0002-6360-9265
FU National Institute on Drug Abuse (NIDA) [R01DA021757, R01DA014948];
National Center on Research Resources [3 M01 RR00425, P20 RR11091]
FX This study is part of the Infant Development, Environment and Lifestyle
(IDEAL) Study, which was conducted with support from the National
Institute on Drug Abuse (NIDA), R01DA021757 (Linda LaGasse, Ph.D.) and
R01DA014948 (Barry Lester, Ph.D.) and in part by the National Center on
Research Resources, Grant # 3 M01 RR00425 and P20 RR11091.
NR 56
TC 23
Z9 24
U1 4
U2 15
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0892-0362
J9 NEUROTOXICOL TERATOL
JI Neurotoxicol. Teratol.
PD JAN-FEB
PY 2011
VL 33
IS 1
SI SI
BP 176
EP 184
DI 10.1016/j.ntt.2010.10.004
PG 9
WC Neurosciences; Toxicology
SC Neurosciences & Neurology; Toxicology
GA 724XN
UT WOS:000287609800020
PM 21256431
ER
PT J
AU Kirby, AC
Nager, CW
Litman, HJ
FitzGerald, MP
Kraus, S
Norton, P
Sirls, L
Rickey, L
Wilson, T
Dandreo, KJ
Shepherd, J
Zimmern, P
AF Kirby, Anna C.
Nager, Charles W.
Litman, Heather J.
FitzGerald, Mary P.
Kraus, Stephen
Norton, Peggy
Sirls, Larry
Rickey, Leslie
Wilson, Tracey
Dandreo, Kimberly J.
Shepherd, Jonathan
Zimmern, Philippe
CA Urinary Incontinence Treatment
TI Perineal Surface Electromyography Does Not Typically Demonstrate
Expected Relaxation During Normal Voiding
SO NEUROUROLOGY AND URODYNAMICS
LA English
DT Article
DE electromyography; pelvic floor; stress urinary incontinence; urethra;
urodynamics; voiding dysfunction
ID PRESSURE-FLOW; STRESS-INCONTINENCE; MUSCLES; WOMEN; OBSTRUCTION;
ELECTRODES; CYSTOMETRY
AB Aims: To describe perineal surface patch electromyography (EMG) activity during urodynamics (UDS) and compare activity between filling and voiding phases and to assess for a relationship between preoperative EMG activity and postoperative voiding symptoms. Methods: 655 women underwent standardized preoperative UDS that included perineal surface EMG prior to undergoing surgery for stress urinary incontinence. Pressure-flow studies were evaluated for abdominal straining and interrupted flow. Quantitative EMG values were extracted from 10 predetermined time-points and compared between fill and void. Qualitative EMG activity was assessed for the percent of time EMG was active during fill and void and for the average amplitude of EMG during fill compared to void. Postoperative voiding dysfunction was defined as surgical revision or catheterization more than 6 weeks after surgery. Fisher's exact test with a 5% two-sided significance level was used to assess differences in EMG activity and postoperative voiding dysfunction. Results: 321 UDS had interpretable EMG studies, of which 131 (41%) had EMG values at all 10 predetermined and annotated time-points. Quantitative and qualitative EMG signals during flow were usually greater than during fill. The prevalence of postoperative voiding dysfunction in subjects with higher preoperative EMG activity during void was not significantly different. Results were similar in the 42 subjects who had neither abdominal straining during void nor interrupted flow. Conclusions: Perineal surface patch EMG did not measure expected pelvic floor and urethral sphincter relaxation during voiding. Preoperative EMG did not predict patients at risk for postoperative voiding dysfunction. Neurourol. Urodynam. 30:1591-1596, 2011. (C) 2011 Wiley Periodicals, Inc.
C1 [Kirby, Anna C.; Nager, Charles W.] Univ Calif San Diego, Dept Reprod Med, San Diego, CA 92103 USA.
[Litman, Heather J.; Dandreo, Kimberly J.] New England Res Inst, Watertown, MA 02172 USA.
[FitzGerald, Mary P.] Loyola Univ, Med Ctr, Dept Obstet & Gynecol, Maywood, IL 60153 USA.
[Kraus, Stephen] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA.
[Norton, Peggy] Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA.
[Sirls, Larry] William Beaumont Hosp, Dept Urol, Royal Oak, MI 48072 USA.
[Rickey, Leslie] Univ Maryland, Dept Urol, Baltimore, MD 21201 USA.
[Wilson, Tracey] Univ Alabama, Dept Urol, Birmingham, AL USA.
[Shepherd, Jonathan] Univ Pittsburgh, Magee Womens Hosp, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15213 USA.
[Zimmern, Philippe] Univ Texas SW, Dept Urol, Dallas, TX USA.
[Urinary Incontinence Treatment] NIDDK, NIH, Bethesda, MD USA.
RP Nager, CW (reprint author), 9350 Campus Point Dr,Suite 2A,Mail Code 0974, La Jolla, CA 92037 USA.
EM cnager@ucsd.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases [U01
DK58225, U01 DK58229, U01 DK58234, U01 DK58231, U01 DK60379, U01
DK60380, U01 DK60393, U01 DK60395, U01 DK60397, U01 DK60401]; National
Institute of Child Health and Human Development; Office of Research in
Women's Health of the National Institutes of Health
FX Grant sponsor: National Institute of Diabetes and Digestive and Kidney
Diseases; Grant numbers: U01 DK58225; U01 DK58229; U01 DK58234; U01
DK58231; U01 DK60379; U01 DK60380; U01 DK60393; U01 DK60395; U01
DK60397; U01 DK60401; Grant sponsor: National Institute of Child Health
and Human Development; Grant sponsor: Office of Research in Women's
Health of the National Institutes of Health.
NR 20
TC 1
Z9 1
U1 1
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0733-2467
J9 NEUROUROL URODYNAM
JI Neurourol. Urodyn.
PY 2011
VL 30
IS 8
BP 1591
EP 1596
DI 10.1002/nau.21080
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA 840FT
UT WOS:000296425200040
PM 21560157
ER
PT J
AU Warnick, JE
LaPorte, JL
Kalueff, AV
AF Warnick, Jason E.
LaPorte, Justin L.
Kalueff, Allan V.
TI Domain interplay in mice and men: New possibilities for the "natural
kinds" theory of emotion
SO NEW IDEAS IN PSYCHOLOGY
LA English
DT Article
DE Domain interplay; Behavioral phenotype; Emotion; Natural kind; Animal
model
ID ANXIETY-DEPRESSION CONTINUUM; ANIMAL-MODELS; NEUROPHENOTYPING RESEARCH;
ENVIRONMENT INTERACTIONS; MOUSE; DISORDERS; AUTISM; BEHAVIORS; RELEVANT;
GENETICS
AB The recent challenge to the long-held assumption that emotions are natural kinds (i.e., discreet naturally-distinguishable phenomena) has raised the necessity for a closer look into the nature of affective research. If emotions are not natural kinds, there will be widespread consequences for the theoretical foundations of behavioral neuroscience and grave implications for the validity of animal models of emotion and affective disorders. This paper presents the evidence against the hypothesis of emotions as natural kinds, and offers the "domain-interplay" concept as a novel and effective experimental method for establishing the theoretical rationale of non-human animal research in the neurosciences. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Warnick, Jason E.] Arkansas Tech Univ, Dept Behav Sci, Russellville, AR 72801 USA.
[LaPorte, Justin L.] NIMH, Clin Sci Lab, Bethesda, MD 20892 USA.
[Kalueff, Allan V.] Tulane Univ, Sch Med, Dept Pharmacol, New Orleans, LA 70112 USA.
RP Warnick, JE (reprint author), Arkansas Tech Univ, Dept Behav Sci, Russellville, AR 72801 USA.
EM jwarnick@atu.edu
RI Warnick, Jason/C-5305-2015
OI Warnick, Jason/0000-0002-9632-0505
NR 44
TC 3
Z9 3
U1 0
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0732-118X
J9 NEW IDEAS PSYCHOL
JI New Ideas Psychol.
PD JAN-APR
PY 2011
VL 29
IS 1
BP 49
EP 56
DI 10.1016/j.newideapsych.2010.01.001
PG 8
WC Psychology, Multidisciplinary; Psychology, Experimental
SC Psychology
GA 682XS
UT WOS:000284436900005
ER
PT S
AU Nagababu, E
Rifkind, JM
AF Nagababu, Enika
Rifkind, Joseph M.
BE McCarthy, HO
Coulter, JA
TI Determination of S-Nitrosothiols in Biological Fluids by
Chemiluminescence
SO NITRIC OXIDE: METHODS AND PROTOCOLS
SE Methods in Molecular Biology
LA English
DT Article; Book Chapter
DE S-nitrosothiols; nitric oxide; ozone-based chemiluminescence assay;
plasma; red blood cells
ID NITRIC-OXIDE; N-NITROSO; PLASMA; REDUCTION; PROTEINS
AB S-nitrosothiols present in nanomolar concentrations in cells and body fluids play an important role in vasodilation, in preventing platelet aggregation, leukocyte adhesion, and for cellular signaling. However, because of the low levels of s-nitrosothiols and interference with other nitric oxide species, reliable assays that measure both high molecular weight and low molecular weight s-nitrosothiols in plasma and red blood cells have been difficult to develop. We have previously developed a sensitive method using Cu(II)-ascorbic acid at a neutral pH, which was specific for s-nitrosothiols without interference of nitrite or other NOx species. However, due to neutral pH foaming, this method was not suitable for determinations in plasma or red blood cells with high protein content. This method has now been modified by using copper (II) chloride (CuCl2) and ascorbic acid in glacial acetic acid. The low pH solves the foaming problem. However, protonation of nitrite under acidic conditions facilitates the formation of s-nitrosothiols. For this method to specifically measure s-nitrosothiols in the sample, the unreacted thiols are blocked by reacting with N-ethylmaleimide and nitrite is blocked by reacting with acidified sulfanilamide before being analyzed by chemiluminescence. Using this method, s-nitrosothiols have been determined in the range of 2 nM to 26 nM (mean +/- SE = 10.18 +/- 2.1) in plasma and up to 88.1 nM (mean +/- SE = 51.27 +/- 10.5) in red blood cells.
C1 [Nagababu, Enika; Rifkind, Joseph M.] NIA, Mol Dynam Sect, NIH, Baltimore, MD 21224 USA.
RP Nagababu, E (reprint author), NIA, Mol Dynam Sect, NIH, Baltimore, MD 21224 USA.
NR 15
TC 12
Z9 15
U1 0
U2 9
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA
SN 1064-3745
BN 978-1-61737-963-5
J9 METHODS MOL BIOL
JI Methods Mol. Biol.
PY 2011
VL 704
BP 27
EP 37
DI 10.1007/978-1-61737-964-2_3
D2 10.1007/978-1-61737-964-2
PG 11
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA BSV21
UT WOS:000285893500003
PM 21161627
ER
PT S
AU Piknova, B
Schechter, AN
AF Piknova, Barbora
Schechter, Alan N.
BE McCarthy, HO
Coulter, JA
TI Measurement of Nitrite in Blood Samples Using the Ferricyanide-Based
Hemoglobin Oxidation Assay
SO NITRIC OXIDE: METHODS AND PROTOCOLS
SE Methods in Molecular Biology
LA English
DT Article; Book Chapter
DE Nitrite; hemoglobin; red blood cell; chemiluminescence
ID BIOLOGICAL SAMPLES; S-NITROSOTHIOLS; PLASMA NITRITE; CHEMILUMINESCENCE;
OXIDE; METABOLITES; NITRATE; NO
AB Nitrite is currently recognized as a biomarker of the state of nitric oxide metabolism. Therefore, assessing nitrite levels in various organs and compartments is an important issue. As nitrite levels in most organs and tissues ate low (in high nanomolar or low micromolar range) several new sensitive methods for quantifying nitrite in various biological samples have been developed. Chemiluminescence, combined with triiodide reducing solution, is currently considered the most sensitive method, allowing quantification in the low nanomolar range of nitrite concentrations. Here, we present an overview of chemiluminescence-based determination of nitrite in blood and blood compartments red blood cells and plasma. We also explain how to preserve the original physiological nitrite concentration in nitrite-hostile environments, such as an excess of hemoglobin in blood.
C1 [Piknova, Barbora; Schechter, Alan N.] NIDDK, Mol Med Branch, NIH, Bethesda, MD 20892 USA.
RP Piknova, B (reprint author), NIDDK, Mol Med Branch, NIH, Bethesda, MD 20892 USA.
OI Schechter, Alan N/0000-0002-5235-9408
FU Intramural NIH HHS [ZIA DK025093-14, ZIA DK025104-06]
NR 13
TC 7
Z9 7
U1 2
U2 3
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA
SN 1064-3745
BN 978-1-61737-963-5
J9 METHODS MOL BIOL
JI Methods Mol. Biol.
PY 2011
VL 704
BP 39
EP 56
DI 10.1007/978-1-61737-964-2_4
D2 10.1007/978-1-61737-964-2
PG 18
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA BSV21
UT WOS:000285893500004
PM 21161628
ER
PT S
AU O'Carroll, IP
Dos Santos, PC
AF O'Carroll, Ina P.
Dos Santos, Patricia C.
BE Ribbe, MW
TI Genomic Analysis of Nitrogen Fixation
SO NITROGEN FIXATION: METHODS AND PROTOCOLS
SE Methods in Molecular Biology
LA English
DT Article; Book Chapter
DE Genome sequencing; genome scanning; genomics; Azotobacter vinelandii;
nitrogen fixation
ID IRON-MOLYBDENUM COFACTOR; AZOTOBACTER-VINELANDII; MUTATIONAL ANALYSIS;
STRUCTURAL GENES; MOFE PROTEIN; PSEUDOMONAS-STUTZERI;
NUCLEOTIDE-SEQUENCE; INDEPENDENT NITROGENASES; RESPIRATORY PROTECTION;
CONTROLLED EXPRESSION
AB Advances in sequencing technology in the past decade have enabled the sequencing of genomes of thousands of organisms including diazotrophs. Genomics have enabled thorough analysis of the gene organization of nitrogen-fixing species, the identification of new genes involved in nitrogen fixation, and the identification of new diazotrophic species. This chapter reviews key characteristics of nitrogen-fixing genomes and methods to identify and analyze genomes of new diazotrophs using genome scanning. This chapter refers to Azotobacter vinelandii, a well-studied nitrogen-fixing organism, as a model for studying nitrogen-fixing genomes. We discuss the main nitrogen fixation genes as well as accessory genes that contribute to diazotrophy. We also review approaches that can be used to modify genomes in order to study nitrogen fixation at the genetic, biochemical, and biophysical level.
C1 [O'Carroll, Ina P.] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA.
[Dos Santos, Patricia C.] Wake Forest Univ, Dept Chem, Wiston Salem, NC USA.
RP O'Carroll, IP (reprint author), NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA.
OI Dos Santos, Patricia/0000-0002-3364-0931
NR 71
TC 4
Z9 4
U1 2
U2 7
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA
SN 1064-3745
BN 978-1-61779-193-2
J9 METHODS MOL BIOL
JI Methods Mol. Biol.
PY 2011
VL 766
BP 49
EP 65
DI 10.1007/978-1-61779-194-9_4
D2 10.1007/978-1-61779-194-9
PG 17
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA BWP54
UT WOS:000294445200004
PM 21833860
ER
PT J
AU Hu, TCC
Chuang, KH
Yanasak, N
Koretsky, A
AF Hu, Tom C. -C.
Chuang, Kai-Hsiang
Yanasak, Nathan
Koretsky, Alan
TI Relationship between blood and myocardium manganese levels during
manganese-enhanced MRI (MEMRI) with T-1 mapping in rats
SO NMR IN BIOMEDICINE
LA English
DT Article
DE T-1 mapping; cardiac MRI; rat; heart; manganese; imaging
ID TRISODIUM MNDPDP INJECTION; RESONANCE-IMAGING MEMRI; III
CLINICAL-TRIALS; INFARCTED MYOCARDIUM; CALCIUM-CHANNEL; CONTRAST AGENTS;
MURINE MODEL; HEPATIC MRI; HEART; VIABILITY
AB Manganese ions (Mn2+) enter viable myocardial cells via voltage-gated calcium channels. Because of its shortening of T-1 and its relatively long half-life in cells, Mn2+ can serve as an intracellular molecular contrast agent to study indirect calcium influx into the myocardium. One major concern in using Mn2+ is its sensitivity over a limited range of concentrations employing T-1-weighted images for visualization, which limits its potential in quantitative techniques. Therefore, this study assessed the implementation of a T-1 mapping method for cardiac manganese-enhanced MRI to enable a quantitative estimate of the influx of Mn2+ over a wide range of concentrations in male Sprague-Dawley rats. This MRI method was used to compare the relationship between T-1 changes in the heart as a function of myocardium and blood Mn2+ levels. Results showed a biphasic relationship between Delta R-1 and the total Mn2+ infusion dose. Nonlinear relationships were observed between the total Mn2+ infusion dose versus blood levels and left ventricular free wall Delta R-1. At low blood levels of Mn2+, there was proportionally less cardiac enhancement seen than at higher levels of blood Mn2+. We hypothesize that Mn2+ blood levels increase as a result of rate-limiting excretion by the liver and kidneys at these higher Mn2+ doses. Copyright (C) 2010 John Wiley & Sons, Ltd.
C1 [Hu, Tom C. -C.; Yanasak, Nathan] Med Coll Georgia, Dept Radiol, Augusta, GA 30912 USA.
[Hu, Tom C. -C.; Chuang, Kai-Hsiang; Koretsky, Alan] NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
RP Hu, TCC (reprint author), Med Coll Georgia, Dept Radiol, 1410 Laney Walker Blvd,CN-3155, Augusta, GA 30912 USA.
EM thu@mail.mcg.edu
RI Koretsky, Alan/C-7940-2015;
OI Koretsky, Alan/0000-0002-8085-4756; Chuang,
Kai-Hsiang/0000-0002-8356-0657
FU National Institutes of Health (NIH); National Institute of Neurological
Disorders and Stroke (NINDS)
FX This research was supported (in part) by the Intramural Research Program
of the National Institutes of Health (NIH) and the National Institute of
Neurological Disorders and Stroke (NINDS). The authors thank N.
Bouraoud, D. Straus, D. Despres, G. A. MacGowan, C. Du, K. Hendrich,
M.-T. Li and A. Schumacher for stimulating discussions, inputs and
technical assistance. The authors would also like to thank Mrs Mary
Barbier for editorial assistance with this paper.
NR 34
TC 7
Z9 7
U1 0
U2 2
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 JAN
PY 2011
VL 24
IS 1
BP 46
EP 53
DI 10.1002/nbm.1554
PG 8
WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
GA 718GY
UT WOS:000287110300005
PM 20665900
ER
PT J
AU Bandele, OJ
Wang, XT
Campbell, MR
Pittman, GS
Bell, DA
AF Bandele, Omari J.
Wang, Xuting
Campbell, Michelle R.
Pittman, Gary S.
Bell, Douglas A.
TI Human single-nucleotide polymorphisms alter p53 sequence-specific
binding at gene regulatory elements
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID BREAST-CANCER CELLS; TRANSCRIPTION-FACTOR; DNA-DAMAGE; HUMAN GENOME;
RESPONSE-ELEMENTS; PROMOTER; SITES; EXPRESSION; NETWORK; TARGETS
AB p53 coordinates the expression of an intricate network of genes in response to stress signals. Sequence-specific DNA binding is essential for p53-mediated tumor suppression. We evaluated the impact of single-nucleotide polymorphisms (SNPs) in p53 response elements (p53RE) on DNA binding and gene expression in response to DNA damage. Using a bioinformatics approach based on incorporating p53 binding strength into a position weight matrix, we selected 32 SNPs in putative and validated p53REs. The microsphere assay for protein-DNA binding (MAPD) and allele-specific expression analysis was employed to assess the impact of SNPs on p53-DNA binding and gene expression, respectively. Comparing activated p53 binding in nuclear extracts from doxorubicin- or ionizing radiation (IR)-treated human cells, we observed little difference in binding profiles. Significant p53 binding was observed for most polymorphic REs and several displayed binding comparable to the p21 RE. SNP alleles predicted to lower p53 binding indeed reduced binding in 25 of the 32 sequences. Chromatin immunoprecipitation-sequencing in lymphoblastoid cells confirmed p53 binding to seven polymorphic p53 REs in response to doxorubicin. In addition, five polymorphisms were associated with altered gene expression following doxorubicin treatment. Our findings demonstrate an effective strategy to identify and evaluate SNPs that may alter p53-mediated stress responses.
C1 [Bandele, Omari J.; Wang, Xuting; Campbell, Michelle R.; Pittman, Gary S.; Bell, Douglas A.] Natl Inst Environm Hlth Sci, Environm Genom Grp, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Bell, DA (reprint author), Natl Inst Environm Hlth Sci, Environm Genom Grp, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA.
EM bell1@niehs.nih.gov
OI Wang, Xuting/0000-0001-6781-8008
FU National Institute of Environmental Health Sciences, National Institutes
of Health [ZO1-ES-100475-M-0001, ZO1-ES065079-15]; National Institute of
Environmental Health Sciences
FX The Intramural Research Program of the National Institute of
Environmental Health Sciences, National Institutes of Health
(ZO1-ES-100475-M-0001 and ZO1-ES065079-15). Funding for open access
charge: The Intramural Research Program, National Institute of
Environmental Health Sciences.
NR 54
TC 16
Z9 17
U1 0
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN
PY 2011
VL 39
IS 1
BP 178
EP 189
DI 10.1093/nar/gkq764
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 703VD
UT WOS:000286008500019
PM 20817676
ER
PT J
AU Midon, M
Schafer, P
Pingoud, A
Ghosh, M
Moon, AF
Cuneo, MJ
London, RE
Meiss, G
AF Midon, Marika
Schaefer, Patrick
Pingoud, Alfred
Ghosh, Mahua
Moon, Andrea F.
Cuneo, Matthew J.
London, Robert E.
Meiss, Gregor
TI Mutational and biochemical analysis of the DNA-entry nuclease EndA from
Streptococcus pneumoniae
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID GROUP-A STREPTOCOCCUS; NEUTROPHIL EXTRACELLULAR TRAPS;
SERRATIA-MARCESCENS NUCLEASE; SUGAR-NONSPECIFIC NUCLEASE; RAY SOLUTION
SCATTERING; GENETIC TRANSFORMATION; BACILLUS-SUBTILIS; ESCHERICHIA-COLI;
MECHANISM; ANABAENA
AB EndA is a membrane-attached surface-exposed DNA-entry nuclease previously known to be required for genetic transformation of Streptococcus pneumoniae. More recent studies have shown that the enzyme also plays an important role during the establishment of invasive infections by degrading extracellular chromatin in the form of neutrophil extracellular traps (NETs), enabling streptococci to overcome the innate immune system in mammals. As a virulence factor, EndA has become an interesting target for future drug design. Here we present the first mutational and biochemical analysis of recombinant forms of EndA produced either in a cell-free expression system or in Escherichia coli. We identify His160 and Asn191 to be essential for catalysis and Asn182 to be required for stability of EndA. The role of His160 as the putative general base in the catalytic mechanism is supported by chemical rescue of the H160A variant of EndA with imidazole added in excess. Our study paves the way for the identification and development of protein or low-molecular-weight inhibitors for EndA in future high-throughput screening assays.
C1 [Midon, Marika; Schaefer, Patrick; Pingoud, Alfred; Meiss, Gregor] Univ Giessen, Inst Biochem, D-35392 Giessen, Germany.
[Ghosh, Mahua] Indian Inst Sci Educ & Res, Mohanpur 741252, W Bengal, India.
[Moon, Andrea F.; Cuneo, Matthew J.; London, Robert E.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Meiss, G (reprint author), Univ Giessen, Inst Biochem, Heinrich Buff Ring 58, D-35392 Giessen, Germany.
EM gregor.meiss@chemie.bio.uni-giessen.de
RI ID, BioCAT/D-2459-2012;
OI Cuneo, Matthew/0000-0002-1475-6656
FU United States Department of Energy, Office of Science, Office of Basic
Energy Sciences [DE-AC02-98CH10886, W-31-109-Eng-38]; German Research
Foundation (DFG); 'Excellence Cluster Cardio-Pulmonary System' (ECCPS);
Dr -Herbert-Stolzenberg-Stiftung of the Justus-Liebig-University Giessen
FX The authors would like to thank the laboratory of Dr Lin Yang of the X9
beamline, at the National Synchrotron Light Source at Brookhaven
National Laboratory and Dr Liang Guo of the 18-ID BioCat Beamline, at
the Advanced Photon Source at the Argonne National Laboratory, for
assistance with data collection. Use of the X9 beamline is supported by
the United States Department of Energy, Office of Science, Office of
Basic Energy Sciences, under Contract DE-AC02-98CH10886. Use of the
Advanced Photon Source was supported by the U. S. Department of Energy,
Office of Science, Office of Basic Energy Sciences, under Contract No
W-31-109-Eng-38.; German Research Foundation (DFG); the 'Excellence
Cluster Cardio-Pulmonary System' (ECCPS), and the Dr
-Herbert-Stolzenberg-Stiftung of the Justus-Liebig-University Giessen.
Funding for open access charge: German Research Foundation.
NR 43
TC 13
Z9 15
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN
PY 2011
VL 39
IS 2
BP 623
EP 634
DI 10.1093/nar/gkq802
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 712OE
UT WOS:000286675300027
PM 20846957
ER
PT J
AU Barrett, T
Troup, DB
Wilhite, SE
Ledoux, P
Evangelista, C
Kim, IF
Tomashevsky, M
Marshall, KA
Phillippy, KH
Sherman, PM
Muertter, RN
Holko, M
Ayanbule, O
Yefanov, A
Soboleva, A
AF Barrett, Tanya
Troup, Dennis B.
Wilhite, Stephen E.
Ledoux, Pierre
Evangelista, Carlos
Kim, Irene F.
Tomashevsky, Maxim
Marshall, Kimberly A.
Phillippy, Katherine H.
Sherman, Patti M.
Muertter, Rolf N.
Holko, Michelle
Ayanbule, Oluwabukunmi
Yefanov, Andrey
Soboleva, Alexandra
TI NCBI GEO: archive for functional genomics data sets-10 years on
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID GENE-EXPRESSION; INFORMATION
AB A decade ago, the Gene Expression Omnibus (GEO) database was established at the National Center for Biotechnology Information (NCBI). The original objective of GEO was to serve as a public repository for high-throughput gene expression data generated mostly by microarray technology. However, the research community quickly applied microarrays to non-gene-expression studies, including examination of genome copy number variation and genome-wide profiling of DNA-binding proteins. Because the GEO database was designed with a flexible structure, it was possible to quickly adapt the repository to store these data types. More recently, as the microarray community switches to next-generation sequencing technologies, GEO has again adapted to host these data sets. Today, GEO stores over 20 000 microarray- and sequence-based functional genomics studies, and continues to handle the majority of direct high-throughput data submissions from the research community. Multiple mechanisms are provided to help users effectively search, browse, download and visualize the data at the level of individual genes or entire studies. This paper describes recent database enhancements, including new search and data representation tools, as well as a brief review of how the community uses GEO data. GEO is freely accessible at http://www.ncbi.nlm.nih.gov/geo/.
C1 [Barrett, Tanya; Troup, Dennis B.; Wilhite, Stephen E.; Ledoux, Pierre; Evangelista, Carlos; Kim, Irene F.; Tomashevsky, Maxim; Marshall, Kimberly A.; Phillippy, Katherine H.; Sherman, Patti M.; Muertter, Rolf N.; Holko, Michelle; Ayanbule, Oluwabukunmi; Yefanov, Andrey; Soboleva, Alexandra] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
RP Barrett, T (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, 45 Ctr Dr, Bethesda, MD 20892 USA.
EM barrett@ncbi.nlm.nih.gov
FU National Institutes of Health, National Library of Medicine
FX Funding for open access charge: The Intramural Research Program of the
National Institutes of Health, National Library of Medicine.
NR 22
TC 208
Z9 211
U1 1
U2 14
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN
PY 2011
VL 39
SU 1
BP D1005
EP D1010
DI 10.1093/nar/gkq1184
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 701PA
UT WOS:000285831700158
ER
PT J
AU Benson, DA
Karsch-Mizrachi, I
Lipman, DJ
Ostell, J
Sayers, EW
AF Benson, Dennis A.
Karsch-Mizrachi, Ilene
Lipman, David J.
Ostell, James
Sayers, Eric W.
TI GenBank
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID DATABASE; GENERATION; ARCHIVE
AB GenBank (R) is a comprehensive database that contains publicly available nucleotide sequences for more than 380 000 organisms named at the genus level or lower, obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects, including whole genome shotgun (WGS) and environmental sampling projects. Most submissions are made using the web-based BankIt or standalone Sequin programs, and accession numbers are assigned by GenBank staff upon receipt. Daily data exchange with the European Nucleotide Archive (ENA) and the DNA Data Bank of Japan (DDBJ) ensures worldwide coverage. GenBank is accessible through the NCBI Entrez retrieval system that integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and the biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available by FTP. To access GenBank and its related retrieval and analysis services, begin at the NCBI Homepage: www.ncbi.nlm.nih.gov.
C1 [Benson, Dennis A.; Karsch-Mizrachi, Ilene; Lipman, David J.; Ostell, James; Sayers, Eric W.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
RP Sayers, EW (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
EM sayers@ncbi.nlm.nih.gov
FU National Institutes of Health, National Library of Medicine
FX Funding for open access charge: Intramural Research Program of the
National Institutes of Health, National Library of Medicine.
NR 10
TC 392
Z9 404
U1 5
U2 19
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN
PY 2011
VL 39
SU 1
BP D32
EP D37
DI 10.1093/nar/gkq1079
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 701PA
UT WOS:000285831700008
PM 21071399
ER
PT J
AU Cer, RZ
Bruce, KH
Mudunuri, US
Yi, M
Volfovsky, N
Luke, BT
Bacolla, A
Collins, JR
Stephens, RM
AF Cer, Regina Z.
Bruce, Kevin H.
Mudunuri, Uma S.
Yi, Ming
Volfovsky, Natalia
Luke, Brian T.
Bacolla, Albino
Collins, Jack R.
Stephens, Robert M.
TI Non-B DB: a database of predicted non-B DNA-forming motifs in mammalian
genomes
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID SUPERCOILING IN-VIVO; CRUCIFORM FORMATION; HUMAN GENES; SEQUENCES;
REARRANGEMENTS; COMPLEX; CONFORMATIONS; RECOMBINATION; REPEATS; BINDING
AB Although the capability of DNA to form a variety of non-canonical (non-B) structures has long been recognized, the overall significance of these alternate conformations in biology has only recently become accepted en masse. In order to provide access to genome-wide locations of these classes of predicted structures, we have developed non-B DB, a database integrating annotations and analysis of non-B DNA-forming sequence motifs. The database provides the most complete list of alternative DNA structure predictions available, including Z-DNA motifs, quadruplex-forming motifs, inverted repeats, mirror repeats and direct repeats and their associated subsets of cruciforms, triplex and slipped structures, respectively. The database also contains motifs predicted to form static DNA bends, short tandem repeats and homo(purine center dot pyrimidine) tracts that have been associated with disease. The database has been built using the latest releases of the human, chimp, dog, macaque and mouse genomes, so that the results can be compared directly with other data sources. In order to make the data interpretable in a genomic context, features such as genes, single-nucleotide polymorphisms and repetitive elements (SINE, LINE, etc.) have also been incorporated. The database is accessed through query pages that produce results with links to the UCSC browser and a GBrowse-based genomic viewer. It is freely accessible at http://nonb.abcc.ncifcrf.gov.
C1 [Cer, Regina Z.; Bruce, Kevin H.; Mudunuri, Uma S.; Yi, Ming; Volfovsky, Natalia; Luke, Brian T.; Bacolla, Albino; Collins, Jack R.; Stephens, Robert M.] NCI, Adv Biomed Comp Ctr, Informat Syst Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Bacolla, Albino] Univ Texas MD Anderson Canc Ctr, Dept Carcinogenesis, Div Sci Pk Res, Smithville, TX 78957 USA.
RP Stephens, RM (reprint author), NCI, Adv Biomed Comp Ctr, Informat Syst Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
EM stephensr@mail.nih.gov
RI Bacolla, Albino/N-3877-2013
OI Bacolla, Albino/0000-0003-0206-8423
FU Center for Biomedical Informatics and Information Technology
(CBIIT)/Cancer Biomedical Informatics Grid (caBIG) ISRCE [09-260];
National Cancer Institute/National Institutes of Health
[HHSN261200800001E]
FX Center for Biomedical Informatics and Information Technology
(CBIIT)/Cancer Biomedical Informatics Grid (caBIG) ISRCE yellow task
#09-260 to NCI-Frederick and National Cancer Institute/National
Institutes of Health contract HHSN261200800001E (to A. B.). Funding for
open access charge: National Cancer Institute/National Institutes of
Health contract HHSN261200800001E.
NR 57
TC 30
Z9 30
U1 1
U2 12
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN
PY 2011
VL 39
SU 1
BP D383
EP D391
DI 10.1093/nar/gkq1170
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 701PA
UT WOS:000285831700064
PM 21097885
ER
PT J
AU Fingerman, IM
McDaniel, L
Zhang, XA
Ratzat, W
Hassan, T
Jiang, ZF
Cohen, RF
Schuler, GD
AF Fingerman, Ian M.
McDaniel, Lee
Zhang, Xuan
Ratzat, Walter
Hassan, Tarek
Jiang, Zhifang
Cohen, Robert F.
Schuler, Gregory D.
TI NCBI Epigenomics: a new public resource for exploring epigenomic data
sets
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID EPIGENETIC INHERITANCE; CANCER; CHROMATIN; GENOME
AB The Epigenomics database at the National Center for Biotechnology Information (NCBI) is a new resource that has been created to serve as a comprehensive public resource for whole-genome epigenetic data sets Epigenetics is the study of stable and heritable changes in gene expression that occur independently of the primary DNA sequence. Epigenetic mechanisms include post-translational modifications of histones, DNA methylation, chromatin conformation and non-coding RNAs. It has been observed that misregulation of epigenetic processes has been associated with human disease. We have constructed the new resource by selecting the subset of epigenetics-specific data from general-purpose archives, such as the Gene Expression Omnibus, and Sequence Read Archives, and then subjecting them to further review, annotation and reorganization. Raw data is processed and mapped to genomic coordinates to generate 'tracks' that are a visual representation of the data. These data tracks can be viewed using popular genome browsers or downloaded for local analysis. The Epigenomics resource also provides the user with a unique interface that allows for intuitive browsing and searching of data sets based on biological attributes. Currently, there are 69 studies, 337 samples and over 1100 data tracks from five well-studied species that are viewable and downloadable in Epigenomics.
C1 [Fingerman, Ian M.; McDaniel, Lee; Zhang, Xuan; Ratzat, Walter; Hassan, Tarek; Jiang, Zhifang; Cohen, Robert F.; Schuler, Gregory D.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
RP Schuler, GD (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, 45 Ctr Dr, Bethesda, MD 20892 USA.
EM schuler@ncbi.nlm.nih.gov
FU National Institutes of Health, National Library of Medicine
FX Funding for open access charge: The Intramural Research Program of the
National Institutes of Health, National Library of Medicine.
NR 18
TC 30
Z9 30
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN
PY 2011
VL 39
SU 1
BP D908
EP D912
DI 10.1093/nar/gkq1146
PG 5
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 701PA
UT WOS:000285831700142
PM 21075792
ER
PT J
AU Galperin, MY
Cochrane, GR
AF Galperin, Michael Y.
Cochrane, Guy R.
TI The 2011 Nucleic Acids Research Database Issue and the online Molecular
Biology Database Collection
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID RNA MODIFICATION DATABASE; PROTEIN DATA-BANK; COMPREHENSIVE DATABASE;
UPDATE; CANCER; GENES; INFORMATION; KNOWLEDGE; SEQUENCE
AB The current 18th Database Issue of Nucleic Acids Research features descriptions of 96 new and 83 updated online databases covering various areas of molecular biology. It includes two editorials, one that discusses COMBREX, a new exciting project aimed at figuring out the functions of the 'conserved hypothetical' proteins, and one concerning BioDBcore, a proposed description of the 'minimal information about a biological database'. Papers from the members of the International Nucleotide Sequence Database collaboration (INSDC) describe each of the participating databases, DDBJ, ENA and GenBank, principles of data exchange within the collaboration, and the recently established Sequence Read Archive. A testament to the longevity of databases, this issue includes updates on the RNA modification database, Definition of Secondary Structure of Proteins (DSSP) and Homology-derived Secondary Structure of Proteins (HSSP) databases, which have not been featured here in > 12 years. There is also a block of papers describing recent progress in protein structure databases, such as Protein DataBank (PDB), PDB in Europe (PDBe), CATH, SUPERFAMILY and others, as well as databases on protein structure modeling, protein-protein interactions and the organization of inter-protein contact sites. Other highlights include updates of the popular gene expression databases, GEO and ArrayExpress, several cancer gene databases and a detailed description of the UK PubMed Central project. The Nucleic Acids Research online Database Collection, available at: http://www.oxfordjournals.org/nar/database/a, now lists 1330 carefully selected molecular biology databases. The full content of the Database Issue is freely available online at the Nucleic Acids Research web site http://nar.oxfordjournals.org/).
C1 [Galperin, Michael Y.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
[Cochrane, Guy R.] EMBL European Bioinformat Inst, Cambridge CB10 1SD, England.
RP Galperin, MY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
EM galperin@ncbi.nlm.nih.gov
RI Galperin, Michael/B-5859-2013;
OI Galperin, Michael/0000-0002-2265-5572; Cochrane, Guy/0000-0001-7954-7057
FU US National Institutes of Health; European Molecular Biology Laboratory;
Oxford University Press
FX Intramural Research Program of the US National Institutes of Health (to
M.Y.G.); European Molecular Biology Laboratory (to G. R. C.). Funding
for open access charge: Waived by Oxford University Press.
NR 61
TC 40
Z9 40
U1 0
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN
PY 2011
VL 39
SU 1
BP D1
EP D6
DI 10.1093/nar/gkq1243
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 701PA
UT WOS:000285831700001
PM 21177655
ER
PT J
AU Gaudet, P
Bairoch, A
Field, D
Sansone, SA
Taylor, C
Attwood, TK
Bateman, A
Blake, JA
Bult, CJ
Cherry, JM
Chisholm, RL
Cochrane, G
Cook, CE
Eppig, JT
Galperin, MY
Gentleman, R
Goble, CA
Gojobori, T
Hancock, JM
Howe, DG
Imanishi, T
Kelso, J
Landsman, D
Lewis, SE
Karsch-Mizrachi, I
Orchard, S
Ouellette, BFF
Ranganathan, S
Richardson, L
Rocca-Serra, P
Schofield, PN
Smedley, D
Southan, C
Tan, TW
Tatusova, T
Whetzel, PL
White, O
Yamasaki, C
AF Gaudet, Pascale
Bairoch, Amos
Field, Dawn
Sansone, Susanna-Assunta
Taylor, Chris
Attwood, Teresa K.
Bateman, Alex
Blake, Judith A.
Bult, Carol J.
Cherry, J. Michael
Chisholm, Rex L.
Cochrane, Guy
Cook, Charles E.
Eppig, Janan T.
Galperin, Michael Y.
Gentleman, Robert
Goble, Carole A.
Gojobori, Takashi
Hancock, John M.
Howe, Douglas G.
Imanishi, Tadashi
Kelso, Janet
Landsman, David
Lewis, Suzanna E.
Karsch-Mizrachi, Ilene
Orchard, Sandra
Ouellette, B. F. Francis
Ranganathan, Shoba
Richardson, Lorna
Rocca-Serra, Philippe
Schofield, Paul N.
Smedley, Damian
Southan, Christopher
Tan, Tin Wee
Tatusova, Tatiana
Whetzel, Patricia L.
White, Owen
Yamasaki, Chisato
CA BioDBCore Working Grp
TI Towards BioDBcore: a community-defined information specification for
biological databases
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID BIOINFORMATICS; RESOURCES
AB The present article proposes the adoption of a community-defined, uniform, generic description of the core attributes of biological databases, BioDBCore. The goals of these attributes are to provide a general overview of the database landscape, to encourage consistency and interoperability between resources and to promote the use of semantic and syntactic standards. BioDBCore will make it easier for users to evaluate the scope and relevance of available resources. This new resource will increase the collective impact of the information present in biological databases.
C1 [Gaudet, Pascale; Bairoch, Amos] CMU, Swiss Inst Bioinformat, CH-1211 Geneva 4, Switzerland.
[Gaudet, Pascale; Chisholm, Rex L.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Field, Dawn] NERC, Ctr Ecol & Hydrol, Oxford OX1 3SR, England.
[Sansone, Susanna-Assunta; Cook, Charles E.; Rocca-Serra, Philippe] Univ Oxford, Oxford E Res Ctr, Oxford OX1 3QG, England.
[Taylor, Chris; Cochrane, Guy; Orchard, Sandra; Smedley, Damian] European Bioinformat Inst, European Mol Biol Lab EMBL Outstn, Cambridge CB10 1SD, England.
[Attwood, Teresa K.] Univ Manchester, Fac Life Sci, Manchester M13 9PT, Lancs, England.
[Attwood, Teresa K.; Goble, Carole A.] Univ Manchester, Sch Comp Sci, Manchester M13 9PT, Lancs, England.
[Bateman, Alex] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
[Blake, Judith A.; Bult, Carol J.; Eppig, Janan T.] Jackson Lab, Bar Harbor, ME 04609 USA.
[Cherry, J. Michael] Stanford Univ, Dept Genet, Stanford, CA 94305 USA.
[Galperin, Michael Y.; Karsch-Mizrachi, Ilene; Tatusova, Tatiana] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
[Gentleman, Robert] Genentech Inc, San Francisco, CA 94080 USA.
[Gentleman, Robert; Kelso, Janet; Landsman, David; Ouellette, B. F. Francis] Oxford Univ Press, DATABASE, Journal Biol Databases & Curat, Oxford OX2 6DP, England.
[Gojobori, Takashi; Imanishi, Tadashi; Yamasaki, Chisato] Natl Inst Adv Ind Sci & Technol, Biomed Informat Res Ctr, Koto Ku, Tokyo 1350064, Japan.
[Gojobori, Takashi] Natl Inst Genet, Ctr Informat Biol, Mishima, Shizuoka 4118540, Japan.
[Gojobori, Takashi] Natl Inst Genet, DNA Data Bank Japan, Mishima, Shizuoka 4118540, Japan.
[Hancock, John M.] MRC Harwell, Mammalian Genet Unit, Didcot OX11 0RD, Oxon, England.
[Howe, Douglas G.] 5291 Univ Oregon, Zebrafish Model Organism Database, Eugene, OR 97401 USA.
[Kelso, Janet] Max Planck Inst Evolutionary Anthropol, Dept Evolutionary Genet, Leipzig, Germany.
[Lewis, Suzanna E.] Univ Calif Berkeley, Lawrence Berkeley Lab, Genom Div, Berkeley, CA 94720 USA.
[Ouellette, B. F. Francis] Ontario Inst Canc Res, Toronto, ON M5G 0A3, Canada.
[Ranganathan, Shoba] Macquarie Univ, Dept Chem & Biomol Sci, Sydney, NSW 2109, Australia.
[Ranganathan, Shoba; Tan, Tin Wee] Natl Univ Singapore, Dept Biochem, Yong Loo Lin Sch Med, Singapore 117548, Singapore.
[Richardson, Lorna] Western Gen Hosp, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland.
[Schofield, Paul N.] Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge CB2 3EG, England.
[Southan, Christopher] ChrisDS Consulting, Gothenburg, Sweden.
[Whetzel, Patricia L.] Stanford Univ, Stanford Ctr Biomed Informat Res, Natl Ctr Biomed Ontol, Stanford, CA 94305 USA.
[White, Owen] Univ Maryland, Inst Genome Sci, Sch Med, Baltimore, MD 21201 USA.
RP Gaudet, P (reprint author), CMU, Swiss Inst Bioinformat, 1 Rue Michel Servet, CH-1211 Geneva 4, Switzerland.
EM pascale.gaudet@isb-sib.ch
RI Field, Dawn/C-1653-2010; Bateman, Alex/E-6518-2011; Hancock,
John/A-2442-2009; Galperin, Michael/B-5859-2013; Tan, Tin
Wee/B-8963-2009;
OI Bairoch, Amos/0000-0003-2826-6444; Landsman, David/0000-0002-9819-6675;
Orchard, Sandra/0000-0002-8878-3972; Blake, Judith/0000-0001-8522-334X;
Southan, Christopher/0000-0001-9580-0446; Hancock,
John/0000-0003-2991-2217; Galperin, Michael/0000-0002-2265-5572; Tan,
Tin Wee/0000-0002-4062-2854; Cherry, J. Michael/0000-0001-9163-5180;
Ranganathan, Shoba/0000-0002-8290-813X; Bateman,
Alex/0000-0002-6982-4660; Lewis, Suzanna/0000-0002-8343-612X; Goble,
Carole/0000-0003-1219-2137; Richardson, Lorna/0000-0002-3655-5660;
Cochrane, Guy/0000-0001-7954-7057
FU Biotechnology and Biological Sciences Research Council [BB/E025080/1,
BB/F01046X/1, BB/I000771/1]; Intramural NIH HHS [Z99 LM999999]; Medical
Research Council [MC_U127527203, MC_U142684171]; NHGRI NIH HHS [U41
HG000330]; NIGMS NIH HHS [R01 GM087371, R01 GM064426, R01 GM064426-10,
R01 GM087371-03]
NR 12
TC 23
Z9 23
U1 1
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN
PY 2011
VL 39
SU 1
BP D7
EP D10
DI 10.1093/nar/gkq1173
PG 4
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 701PA
UT WOS:000285831700002
PM 21097465
ER
PT J
AU Leinonen, R
Sugawara, H
Shumway, M
AF Leinonen, Rasko
Sugawara, Hideaki
Shumway, Martin
CA Int Nucleotide Sequence Database C
TI The Sequence Read Archive
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
AB The combination of significantly lower cost and increased speed of sequencing has resulted in an explosive growth of data submitted into the primary next-generation sequence data archive, the Sequence Read Archive (SRA). The preservation of experimental data is an important part of the scientific record, and increasing numbers of journals and funding agencies require that next-generation sequence data are deposited into the SRA. The SRA was established as a public repository for the next-generation sequence data and is operated by the International Nucleotide Sequence Database Collaboration (INSDC). INSDC partners include the National Center for Biotechnology Information (NCBI), the European Bioinformatics Institute (EBI) and the DNA Data Bank of Japan (DDBJ). The SRA is accessible at http://www.ncbi.nlm.nih.gov/Traces/sra from NCBI, at http://www.ebi.ac.uk/ena from EBI and at http://trace.ddbj.nig.ac.jp from DDBJ. In this article, we present the content and structure of the SRA, detail our support for sequencing platforms and provide recommended data submission levels and formats. We also briefly outline our response to the challenge of data growth.
C1 [Leinonen, Rasko] European Bioinformat Inst, Cambridge CB10 1SD, England.
[Sugawara, Hideaki] Res Org Informat & Syst, Ctr Informat Biol, Mishima, Shizuoka 4118540, Japan.
[Sugawara, Hideaki] Res Org Informat & Syst, DNA Data Bank Japan, Natl Inst Genet, Mishima, Shizuoka 4118540, Japan.
[Shumway, Martin] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
RP Leinonen, R (reprint author), European Bioinformat Inst, Wellcome Trust Genome Campus, Cambridge CB10 1SD, England.
EM rasko@ebi.ac.uk
OI Cochrane, Guy/0000-0001-7954-7057; Leinonen, Rasko/0000-0002-2639-7187
FU European Molecular Biology Laboratory; European Commission; Wellcome
Trust; Ministry of Education, Culture, Sports, Science and Technology of
Japan; NIH, National Library of Medicine
FX European Molecular Biology Laboratory, European Commission and the
Wellcome Trust; Ministry of Education, Culture, Sports, Science and
Technology of Japan (to D.D.B.J.'s work on SRA and Trace Archive);
Intramural Research Program of the NIH, National Library of Medicine (to
NCBI's SRA work). Funding for open access charge: European Molecular
Biology Laboratory.
NR 9
TC 208
Z9 210
U1 3
U2 25
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN
PY 2011
VL 39
SU 1
BP D19
EP D21
DI 10.1093/nar/gkq1019
PG 3
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 701PA
UT WOS:000285831700005
PM 21062823
ER
PT J
AU Maglott, D
Ostell, J
Pruitt, KD
Tatusova, T
AF Maglott, Donna
Ostell, Jim
Pruitt, Kim D.
Tatusova, Tatiana
TI Entrez Gene: gene-centered information at NCBI
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
AB Entrez Gene (http://www.ncbi.nlm.nih.gov/gene) is National Center for Biotechnology Information (NCBI)'s database for gene-specific information. Entrez Gene maintains records from genomes which have been completely sequenced, which have an active research community to submit gene-specific information, or which are scheduled for intense sequence analysis. The content represents the integration of curation and automated processing from NCBI's Reference Sequence project (RefSeq), collaborating model organism databases, consortia such as Gene Ontology and other databases within NCBI. Records in Entrez Gene are assigned unique, stable and tracked integers as identifiers. The content (nomenclature, genomic location, gene products and their attributes, markers, phenotypes and links to citations, sequences, variation details, maps, expression, homologs, protein domains and external databases) is available via interactive browsing through NCBI's Entrez system, via NCBI's Entrez programming utilities (E-Utilities) and for bulk transfer by FTP.
C1 [Maglott, Donna; Ostell, Jim; Pruitt, Kim D.; Tatusova, Tatiana] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Rockville, MD 20852 USA.
RP Maglott, D (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Rockville, MD 20852 USA.
EM maglott@ncbi.nlm.nih.gov
FU National Institutes of Health; National Library of Medicine
FX Funding for open access charge: The Intramural Research Program of the
National Institutes of Health; National Library of Medicine.
NR 9
TC 290
Z9 295
U1 0
U2 21
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN
PY 2011
VL 39
SU 1
BP D52
EP D57
DI 10.1093/nar/gkq1237
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 701PA
UT WOS:000285831700010
PM 21115458
ER
PT J
AU Marchler-Bauer, A
Lu, SN
Anderson, JB
Chitsaz, F
Derbyshire, MK
DeWeese-Scott, C
Fong, JH
Geer, LY
Geer, RC
Gonzales, NR
Gwadz, M
Hurwitz, DI
Jackson, JD
Ke, ZX
Lanczycki, CJ
Lu, F
Marchler, GH
Mullokandov, M
Omelchenko, MV
Robertson, CL
Song, JS
Thanki, N
Yamashita, RA
Zhang, DC
Zhang, NG
Zheng, CJ
Bryant, SH
AF Marchler-Bauer, Aron
Lu, Shennan
Anderson, John B.
Chitsaz, Farideh
Derbyshire, Myra K.
DeWeese-Scott, Carol
Fong, Jessica H.
Geer, Lewis Y.
Geer, Renata C.
Gonzales, Noreen R.
Gwadz, Marc
Hurwitz, David I.
Jackson, John D.
Ke, Zhaoxi
Lanczycki, Christopher J.
Lu, Fu
Marchler, Gabriele H.
Mullokandov, Mikhail
Omelchenko, Marina V.
Robertson, Cynthia L.
Song, James S.
Thanki, Narmada
Yamashita, Roxanne A.
Zhang, Dachuan
Zhang, Naigong
Zheng, Chanjuan
Bryant, Stephen H.
TI CDD: a Conserved Domain Database for the functional annotation of
proteins
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID GENOMES; SEARCH
AB NCBI's Conserved Domain Database (CDD) is a resource for the annotation of protein sequences with the location of conserved domain footprints, and functional sites inferred from these footprints. CDD includes manually curated domain models that make use of protein 3D structure to refine domain models and provide insights into sequence/structure/function relationships. Manually curated models are organized hierarchically if they describe domain families that are clearly related by common descent. As CDD also imports domain family models from a variety of external sources, it is a partially redundant collection. To simplify protein annotation, redundant models and models describing homologous families are clustered into superfamilies. By default, domain footprints are annotated with the corresponding superfamily designation, on top of which specific annotation may indicate high-confidence assignment of family membership. Pre-computed domain annotation is available for proteins in the Entrez/Protein dataset, and a novel interface, Batch CD-Search, allows the computation and download of annotation for large sets of protein queries. CDD can be accessed via http://www.ncbi.nlm.nih.gov/Structure/cdd/cdd.shtml.
C1 [Marchler-Bauer, Aron; Lu, Shennan; Anderson, John B.; Chitsaz, Farideh; Derbyshire, Myra K.; DeWeese-Scott, Carol; Fong, Jessica H.; Geer, Lewis Y.; Geer, Renata C.; Gonzales, Noreen R.; Gwadz, Marc; Hurwitz, David I.; Jackson, John D.; Ke, Zhaoxi; Lanczycki, Christopher J.; Lu, Fu; Marchler, Gabriele H.; Mullokandov, Mikhail; Omelchenko, Marina V.; Robertson, Cynthia L.; Song, James S.; Thanki, Narmada; Yamashita, Roxanne A.; Zhang, Dachuan; Zhang, Naigong; Zheng, Chanjuan; Bryant, Stephen H.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Marchler-Bauer, A (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38 A,Room 8N805,8600 Rockville Pike, Bethesda, MD 20894 USA.
EM bauer@ncbi.nlm.nih.gov
RI Sincan, Murat /A-3794-2010; Geer, Lewis/H-2714-2014;
OI Marchler-Bauer, Aron/0000-0003-1516-0712
FU National Library of Medicine at the National Institutes of Health/DHHS
FX Funding for open access charge: Intramural Research Program of the
National Library of Medicine at the National Institutes of Health/DHHS.
NR 10
TC 1280
Z9 1312
U1 12
U2 124
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN
PY 2011
VL 39
SU 1
BP D225
EP D229
DI 10.1093/nar/gkq1189
PG 5
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 701PA
UT WOS:000285831700038
PM 21109532
ER
PT J
AU Sayers, EW
Barrett, T
Benson, DA
Bolton, E
Bryant, SH
Canese, K
Chetvernin, V
Church, DM
DiCuccio, M
Federhen, S
Feolo, M
Fingerman, IM
Geer, LY
Helmberg, W
Kapustin, Y
Landsman, D
Lipman, DJ
Lu, ZY
Madden, TL
Madej, T
Maglott, DR
Marchler-Bauer, A
Miller, V
Mizrachi, I
Ostell, J
Panchenko, A
Phan, L
Pruitt, KD
Schuler, GD
Sequeira, E
Sherry, ST
Shumway, M
Sirotkin, K
Slotta, D
Souvorov, A
Starchenko, G
Tatusova, TA
Wagner, L
Wang, YL
Wilbur, WJ
Yaschenko, E
Ye, JA
AF Sayers, Eric W.
Barrett, Tanya
Benson, Dennis A.
Bolton, Evan
Bryant, Stephen H.
Canese, Kathi
Chetvernin, Vyacheslav
Church, Deanna M.
DiCuccio, Michael
Federhen, Scott
Feolo, Michael
Fingerman, Ian M.
Geer, Lewis Y.
Helmberg, Wolfgang
Kapustin, Yuri
Landsman, David
Lipman, David J.
Lu, Zhiyong
Madden, Thomas L.
Madej, Tom
Maglott, Donna R.
Marchler-Bauer, Aron
Miller, Vadim
Mizrachi, Ilene
Ostell, James
Panchenko, Anna
Phan, Lon
Pruitt, Kim D.
Schuler, Gregory D.
Sequeira, Edwin
Sherry, Stephen T.
Shumway, Martin
Sirotkin, Karl
Slotta, Douglas
Souvorov, Alexandre
Starchenko, Grigory
Tatusova, Tatiana A.
Wagner, Lukas
Wang, Yanli
Wilbur, W. John
Yaschenko, Eugene
Ye, Jian
TI Database resources of the National Center for Biotechnology Information
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID ONLINE MENDELIAN INHERITANCE; PROTEIN SEQUENCES; NCBI; SEARCH; ENTREZ;
GENE; GENOMES; SYSTEM; KEGG; TOOL
AB In addition to maintaining the GenBank (R) nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides analysis and retrieval resources for the data in GenBank and other biological data made available through the NCBI Web site. NCBI resources include Entrez, the Entrez Programming Utilities, MyNCBI, PubMed, PubMed Central (PMC), Entrez Gene, the NCBI Taxonomy Browser, BLAST, BLAST Link (BLink), Primer-BLAST, COBALT, Electronic PCR, OrfFinder, Splign, ProSplign, RefSeq, UniGene, HomoloGene, ProtEST, dbMHC, dbSNP, dbVar, Epigenomics, Cancer Chromosomes, Entrez Genomes and related tools, the Map Viewer, Model Maker, Evidence Viewer, Trace Archive, Sequence Read Archive, Retroviral Genotyping Tools, HIV-1/Human Protein Interaction Database, Gene Expression Omnibus (GEO), Entrez Probe, GENSAT, Online Mendelian Inheritance in Man (OMIM), Online Mendelian Inheritance in Animals (OMIA), the Molecular Modeling Database (MMDB), the Conserved Domain Database (CDD), the Conserved Domain Architecture Retrieval Tool (CDART), IBIS, Biosystems, Peptidome, OMSSA, Protein Clusters and the PubChem suite of small molecule databases. Augmenting many of the Web applications are custom implementations of the BLAST program optimized to search specialized data sets. All of these resources can be accessed through the NCBI home page at www.ncbi.nlm.nih.gov.
C1 [Sayers, Eric W.; Barrett, Tanya; Benson, Dennis A.; Bolton, Evan; Bryant, Stephen H.; Canese, Kathi; Chetvernin, Vyacheslav; Church, Deanna M.; DiCuccio, Michael; Federhen, Scott; Feolo, Michael; Fingerman, Ian M.; Geer, Lewis Y.; Kapustin, Yuri; Landsman, David; Lipman, David J.; Lu, Zhiyong; Madden, Thomas L.; Madej, Tom; Maglott, Donna R.; Marchler-Bauer, Aron; Miller, Vadim; Mizrachi, Ilene; Ostell, James; Panchenko, Anna; Phan, Lon; Pruitt, Kim D.; Schuler, Gregory D.; Sequeira, Edwin; Sherry, Stephen T.; Shumway, Martin; Sirotkin, Karl; Slotta, Douglas; Souvorov, Alexandre; Starchenko, Grigory; Tatusova, Tatiana A.; Wagner, Lukas; Wang, Yanli; Wilbur, W. John; Yaschenko, Eugene; Ye, Jian] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
[Helmberg, Wolfgang] Med Univ Graz, Univ Clin Blood Grp Serol & Transfus Med, A-8036 Graz, Austria.
RP Sayers, EW (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA.
EM sayers@ncbi.nlm.nih.gov
RI Geer, Lewis/H-2714-2014;
OI Marchler-Bauer, Aron/0000-0003-1516-0712; Landsman,
David/0000-0002-9819-6675
FU National Institutes of Health, National Library of Medicine
FX Funding for open access charge: the Intramural Research Program of the
National Institutes of Health, National Library of Medicine.
NR 65
TC 316
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U1 2
U2 39
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN
PY 2011
VL 39
SU 1
BP D38
EP D51
DI 10.1093/nar/gkq1172
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 701PA
UT WOS:000285831700009
PM 21097890
ER
PT J
AU Yellaboina, S
Tasneem, A
Zaykin, DV
Raghavachari, B
Jothi, R
AF Yellaboina, Sailu
Tasneem, Asba
Zaykin, Dmitri V.
Raghavachari, Balaji
Jothi, Raja
TI DOMINE: a comprehensive collection of known and predicted domain-domain
interactions
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID PROTEIN-PROTEIN INTERACTIONS
AB DOMINE is a comprehensive collection of known and predicted domain-domain interactions (DDIs) compiled from 15 different sources. The updated DOMINE includes 2285 new domain-domain interactions (DDIs) inferred from experimentally characterized high-resolution three-dimensional structures, and about 3500 novel predictions by five computational approaches published over the last 3 years. These additions bring the total number of unique DDIs in the updated version to 26 219 among 5140 unique Pfam domains, a 23% increase compared to 20 513 unique DDIs among 4346 unique domains in the previous version. The updated version now contains 6634 known DDIs, and features a new classification scheme to assign confidence levels to predicted DDIs. DOMINE will serve as a valuable resource to those studying protein and domain interactions. Most importantly, DOMINE will not only serve as an excellent reference to bench scientists testing for new interactions but also to bioinformaticans seeking to predict novel protein-protein interactions based on the DDIs. The contents of the DOMINE are available at http://domine.utdallas.edu.
C1 [Yellaboina, Sailu; Zaykin, Dmitri V.; Jothi, Raja] NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Tasneem, Asba] Duke Univ, Duke Clin Res Inst, Durham, NC 27705 USA.
[Raghavachari, Balaji] Univ Texas Dallas, Dept Comp Sci, Richardson, TX 75083 USA.
RP Jothi, R (reprint author), NIEHS, Biostat Branch, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM jothi@mail.nih.gov
RI Jothi, Raja/G-3780-2015
FU National Institute of Environmental Health Sciences, National Institute
of Health [Z01ES102625-02]
FX This work was supported by the Intramural Research Program of the
National Institute of Environmental Health Sciences, National Institute
of Health (Project number Z01ES102625-02 to R.J.).
NR 23
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U1 1
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN
PY 2011
VL 39
SU 1
BP D730
EP D735
DI 10.1093/nar/gkq1229
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 701PA
UT WOS:000285831700116
PM 21113022
ER
PT J
AU Dorjsuren, D
Kim, D
Maloney, DJ
Wilson, DM
Simeonov, A
AF Dorjsuren, Dorjbal
Kim, Daemyung
Maloney, David J.
Wilson, David M., III
Simeonov, Anton
TI Complementary non-radioactive assays for investigation of human flap
endonuclease 1 activity
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID GENE-EXPRESSION; DNA-REPAIR; PROSTATE-CANCER; AURINTRICARBOXYLIC ACID;
METHYLATING AGENTS; FEN-1; INHIBITORS; CELLS; IDENTIFICATION;
REPLICATION
AB FEN1, a key participant in DNA replication and repair, is the major human flap endonuclease that recognizes and cleaves flap DNA structures. Deficiencies in FEN1 function or deletion of the fen1 gene have profound biological effects, including the suppression of repair of DNA damage incurred from the action of various genotoxic agents. Given the importance of FEN1 in resolving abnormal DNA structures, inhibitors of the enzyme carry a potential as enhancers of DNA-interactive anticancer drugs. To facilitate the studies of FEN1 activity and the search for novel inhibitors, we developed a pair of complementary-readout homogeneous assays utilizing fluorogenic donor/quencher and AlphaScreen chemiluminescence strategies. A previously reported FEN1 inhibitor 3-hydroxy-5-methyl-1-phenylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione displayed equal potency in the new assays, in agreement with its published IC(50). The assays were optimized to a low 4 mu l volume and used to investigate a set of small molecules, leading to the identification of previously-unreported FEN1 inhibitors, among which aurintricarboxylic acid and NSC-13755 (an arylstibonic derivative) displayed submicromolar potency (average IC(50) of 0.59 and 0.93 mu M, respectively). The availability of these simple complementary assays obviates the need for undesirable radiotracer-based assays and should facilitate efforts to develop novel inhibitors for this key biological target.
C1 [Dorjsuren, Dorjbal; Maloney, David J.; Simeonov, Anton] NHGRI, NIH Chem Genom Ctr, NIH, Bethesda, MD 20892 USA.
[Kim, Daemyung] Cheongju Univ, Dept Genet Engn, Cheongju 360764, South Korea.
[Wilson, David M., III] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
RP Simeonov, A (reprint author), NHGRI, NIH Chem Genom Ctr, NIH, Bethesda, MD 20892 USA.
EM asimeono@mail.nih.gov
FU Molecular Libraries Initiative of the National Institutes of Health
Roadmap for Medical Research [1 R03 MH092154-01, U54MH084681]; National
Institute on Aging; National Human Genome Research Institute, National
Institutes of Health; National Institutes of Health
FX Molecular Libraries Initiative of the National Institutes of Health
Roadmap for Medical Research [grants 1 R03 MH092154-01 (D.M.W.III) and
U54MH084681 (to A. S.)]; Intramural Research Programs of National
Institute on Aging and National Human Genome Research Institute,
National Institutes of Health. Funding for open access charge: National
Institutes of Health Intramural funding.
NR 53
TC 17
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U1 0
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN
PY 2011
VL 39
IS 2
AR e11
DI 10.1093/nar/gkq1082
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 712OE
UT WOS:000286675300006
PM 21062821
ER
PT J
AU Cunnane, S
Nugent, S
Roy, M
Courchesne-Loyer, A
Croteau, E
Tremblay, S
Castellano, A
Pifferi, F
Bocti, C
Paquet, N
Begdouri, H
Bentourkia, M
Turcotte, E
Allard, M
Barberger-Gateau, P
Fulop, T
Rapoport, SI
AF Cunnane, Stephen
Nugent, Scott
Roy, Maggie
Courchesne-Loyer, Alexandre
Croteau, Etienne
Tremblay, Sebastien
Castellano, Alex
Pifferi, Fabien
Bocti, Christian
Paquet, Nancy
Begdouri, Hadi
Bentourkia, M'hamed
Turcotte, Eric
Allard, Michele
Barberger-Gateau, Pascale
Fulop, Tamas
Rapoport, Stanley I.
TI Brain fuel metabolism, aging, and Alzheimer's disease
SO NUTRITION
LA English
DT Review
DE Glucose; Ketones; Brain; Aging; Alzheimer's disease; PET; Insulin;
Cognition; Mitochondria
ID POSITRON-EMISSION-TOMOGRAPHY; MILD COGNITIVE IMPAIRMENT;
CEREBRAL-BLOOD-FLOW; POLYUNSATURATED FATTY-ACIDS; KETONE-BODY
METABOLISM; ALTERED GLUCOSE-METABOLISM; CENTRAL-NERVOUS-SYSTEM;
SHORT-TERM STARVATION; FDG LUMPED CONSTANT; INSULIN-RESISTANCE
AB Lower brain glucose metabolism is present before the onset of clinically measurable cognitive decline in two groups of people at risk of Alzheimer's disease-carriers of apolipoprotein E4, and in those with a maternal family history of AD. Supported by emerging evidence from in vitro and animal studies, these reports suggest that brain hypometabolism may precede and therefore contribute to the neuropathologic cascade leading to cognitive decline in AD. The reason brain hypometabolism develops is unclear but may include defects in brain glucose transport, disrupted glycolysis, and/or impaired mitochondrial function. Methodologic issues presently preclude knowing with certainty whether or not aging in the absence of cognitive impairment is necessarily associated with lower brain glucose metabolism. Nevertheless, aging appears to increase the risk of deteriorating systemic control of glucose utilization, which, in turn, may increase the risk of declining brain glucose uptake, at least in some brain regions. A contributing role of deteriorating glucose availability to or metabolism by the brain in AD does not exclude the opposite effect, i.e., that neurodegenerative processes in AD further decrease brain glucose metabolism because of reduced synaptic functionality and hence reduced energy needs, thereby completing a vicious cycle. Strategies to reduce the risk of AD by breaking this cycle should aim to (1) improve insulin sensitivity by improving systemic glucose utilization, or (2) bypass deteriorating brain glucose metabolism using approaches that safely induce mild, sustainable ketonemia. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Cunnane, Stephen; Nugent, Scott; Roy, Maggie; Courchesne-Loyer, Alexandre; Tremblay, Sebastien; Castellano, Alex; Bocti, Christian; Fulop, Tamas] Univ Sherbrooke, Geriatr Inst, Res Ctr Aging, Hlth & Social Serv Ctr, Sherbrooke, PQ J1K 2R1, Canada.
[Cunnane, Stephen; Bocti, Christian; Fulop, Tamas] Univ Sherbrooke, Dept Med, Sherbrooke, PQ J1K 2R1, Canada.
[Cunnane, Stephen; Nugent, Scott; Roy, Maggie; Courchesne-Loyer, Alexandre] Univ Sherbrooke, Dept Physiol & Biophys, Sherbrooke, PQ J1K 2R1, Canada.
[Croteau, Etienne; Tremblay, Sebastien; Paquet, Nancy; Begdouri, Hadi; Bentourkia, M'hamed; Turcotte, Eric] Univ Sherbrooke, Dept Radiobiol & Nucl Med, Sherbrooke, PQ J1K 2R1, Canada.
[Barberger-Gateau, Pascale] Univ Victor Segalen Bordeaux 2, F-33076 Bordeaux, France.
[Barberger-Gateau, Pascale] INSERM, U897, F-33076 Bordeaux, France.
[Rapoport, Stanley I.] NIA, Brain Physiol & Metab Sect, Bethesda, MD 20892 USA.
[Pifferi, Fabien] UMR CNRS MNHN 7179, Brunoy, France.
[Allard, Michele] Ecole Prat Hautes Etud, F-75013 Paris, France.
[Allard, Michele] UMR CNRS 5231, Paris, France.
RP Cunnane, S (reprint author), Univ Sherbrooke, Geriatr Inst, Res Ctr Aging, Hlth & Social Serv Ctr, Sherbrooke, PQ J1K 2R1, Canada.
EM stephen.cunnane@usherbrooke.ca
RI ALLARD, Michele/D-8538-2014
FU Canada Research Chairs secretariat (SCC); CIHR; NSERC; CFI; AFMNet;
Universite de Sherbrooke (Faculty of Medicine and Health Sciences and
the Department of Medicine); Sherbrooke Molecular Imaging Center;
Etienne-Le Bel Clinical Research Centre; Research Center on Aging;
FQRNT; Intramural Program of the National Institute on Aging, National
Institutes of Health, USA
FX The authors declare no conflicts. Financial support for the research
described here that was done by our group came from the Canada Research
Chairs secretariat (SCC), CIHR, NSERC, CFI, AFMNet, Universite de
Sherbrooke (Faculty of Medicine and Health Sciences and the Department
of Medicine), the Sherbrooke Molecular Imaging Center, the Etienne-Le
Bel Clinical Research Centre, and the Research Center on Aging (both
FRSQ funded), and FQRNT (CFQCU program). The contribution of S.I.
Rapoport was entirely supported by the Intramural Program of the
National Institute on Aging, National Institutes of Health, USA.
Excellent assistance was provided by Jennifer Mercier-Tremblay, Melanie
Fortier, Julie Desgagne, Conrad Filteau, Chantal Langevin, Dr. Otman
Sarrhini, and Esteban O Espinosa.
NR 218
TC 150
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U2 43
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0899-9007
J9 NUTRITION
JI Nutrition
PD JAN
PY 2011
VL 27
IS 1
BP 3
EP 20
DI 10.1016/j.nut.2010.07.021
PG 18
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 699JM
UT WOS:000285659700002
PM 21035308
ER
PT J
AU John, EM
Stern, MC
Sinha, R
Koo, J
AF John, Esther M.
Stern, Mariana C.
Sinha, Rashmi
Koo, Jocelyn
TI Meat Consumption, Cooking Practices, Meat Mutagens, and Risk of Prostate
Cancer
SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL
LA English
DT Article
ID HETEROCYCLIC AMINE CONTENT; FOOD FREQUENCY QUESTIONNAIRE; MULTIETHNIC
COHORT; AFRICAN-AMERICANS; ANIMAL PRODUCTS; VARYING DEGREES; PROCESSED
MEAT; UNITED-STATES; COOKED FOODS; DIETARY-FAT
AB Consumption of red meat, particularly well-done meat, has been associated with increased prostate cancer risk. High-temperature cooking methods such as grilling and barbecuing may produce heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs), which are known carcinogens. We assessed the association with meat consumption and estimated HCA and PAH exposure in a population-based case-control study of prostate cancer. Newly diagnosed cases aged 40-79 years (531 advanced cases, 195 localized cases) and 527 controls were asked about dietary intake, including usual meat cooking methods and doneness levels. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariate logistic regression. For advanced prostate cancer, but not localized disease, increased risks were associated with higher consumption of hamburgers (OR = 1.79, CI = 1.10-2.92), processed meat (OR = 1.57, CI = 1.04-2.36), grilled red meat (OR = 1.63, CI = 0.99-2.68), and well-done red meat (OR = 1.52, CI = 0.93-2.46), and intermediate intake of 2-amino-1-methyl1-6-phenylimidazo[4,5-b]pyridine (PhIP) (Quartile 2 vs. 1: OR = 1.41, CI = 0.98-2.01; Quartile 3 vs. 1: OR = 1.42, CI = 0.98-2.04), but not for higher intake. White meat consumption was not associated with prostate cancer. These findings provide further evidence that consumption of processed meat and red meat cooked at high temperature is associated with increased risk of advanced, but not localized, prostate cancer.
C1 [John, Esther M.; Koo, Jocelyn] Canc Prevent Inst Calif, Fremont, CA 94538 USA.
[John, Esther M.] Stanford Univ, Div Epidemiol, Dept Hlth Res & Policy, Sch Med, Stanford, CA 94305 USA.
[John, Esther M.] Stanford Canc Ctr, Stanford, CA USA.
[Stern, Mariana C.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA.
[Sinha, Rashmi] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
RP John, EM (reprint author), Canc Prevent Inst Calif, 2201 Walnut Ave,Suite 300, Fremont, CA 94538 USA.
EM es-ther.john@CPIC.org
RI Sinha, Rashmi/G-7446-2015
OI Sinha, Rashmi/0000-0002-2466-7462
FU California Cancer Research Program [864A-8702-S3514, 99-00527V-10182];
National Cancer Institute, National Institutes of Health [N01-PC-35136];
California Cancer Registry; Public Health Institute [1006128]; Prostate
Cancer Foundation; National Institute of Environmental Health Sciences
[5P30 ES07048]
FX This research was supported by Grants 864A-8702-S3514 and
99-00527V-10182 (to Esther M. John) from the California Cancer Research
Program. Cancer incidence data used in this article have been collected
by the Greater Bay Area Cancer Registry of the Cancer Prevention
Institute of California (formerly the Northern California Cancer
Center), under contract N01-PC-35136 with the National Cancer Institute,
National Institutes of Health, and with support of the California Cancer
Registry, a project of the Cancer Surveillance Section, California
Department of Health Services, under subcontract 1006128 with the Public
Health Institute. Mention of trade names, commercial products, specific
equipment, or organizations does not constitute endorsement, guarantee,
or warranty by the State of California Department of Health Services or
the U.S. Government, nor does it imply approval to the exclusion of
other products. The views expressed in this article represent those of
the authors and do not necessarily reflect the position or policies of
the Cancer Prevention Institute of California, the California Public
Health Institute, the State of California Department of Health Services,
or the U. S. Department of Health and Human Services. Mariana C. Stern
received support from the Prostate Cancer Foundation and Grant 5P30
ES07048 from the National Institute of Environmental Health Sciences.
NR 54
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U2 21
PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS
PI PHILADELPHIA
PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA
SN 0163-5581
J9 NUTR CANCER
JI Nutr. Cancer
PY 2011
VL 63
IS 4
BP 525
EP 537
AR PII 936900387
DI 10.1080/01635581.2011.539311
PG 13
WC Oncology; Nutrition & Dietetics
SC Oncology; Nutrition & Dietetics
GA 768WT
UT WOS:000290970100005
PM 21526454
ER
PT S
AU Baik, M
Yu, JH
Hennighausen, L
AF Baik, Myunggi
Yu, Ji Hoon
Hennighausen, Lothar
BE Surh, YJ
Song, YS
Han, JY
Jun, TW
Na, HK
TI Growth hormone-STAT5 regulation of growth, hepatocellular carcinoma, and
liver metabolism
SO NUTRITION AND PHYSICAL ACTIVITY IN AGING, OBESITY, AND CANCER
SE Annals of the New York Academy of Sciences
LA English
DT Article; Proceedings Paper
CT 2nd International Conference on Nutrition and Physical Activity in
Aging, Obesity, and Cancer (NAPA 2011)
CY FEB 16-19, 2010-2011
CL Gyeongju, SOUTH KOREA
DE growth hormone; STAT5; liver function
ID I GENE-TRANSCRIPTION; LITHOCHOLIC ACID 6-BETA-HYDROXYLASE; SIGNAL
TRANSDUCER; MOUSE-LIVER; MICROARRAY ANALYSIS; CELL-PROLIFERATION;
SKELETAL-MUSCLE; EXPRESSION; STAT5B; ACTIVATION
AB The liver is a primary target of growth hormone (GH). GH signals arc mediated by the transcription factor signal transducer and activator of transcription 5 (STAT5). Here, we focus on recent discoveries about the role of GH-STAT5 signaling in hepatic physiology and pathophysiology. We discuss roles of the GH-STAT5 axis in body growth, lipid metabolism, and the cell cycle pertaining to hepatosteatosis, fibrosis, and hepatocellular carcinoma. Finally, we discuss recent discoveries about the role of GH-STAT5 in sex-specific gene expression and bile acid, steroid, and drug metabolism.
C1 [Yu, Ji Hoon; Hennighausen, Lothar] NIH, Lab Genet & Physiol, Bethesda, MD 20892 USA.
[Baik, Myunggi; Hennighausen, Lothar] Chonnam Natl Univ, WCU RNNM, Dept Mol Biotechnol, Kwangju, South Korea.
RP Hennighausen, L (reprint author), NIH, Lab Genet & Physiol, Bldg 10, Bethesda, MD 20892 USA.
EM lotharh@mail.nih.gov
FU NIH; NRF [R33-10059]; Rural Development Administration, Republic of
Korea [PJ008191032011]
FX This work was funded in part through the Intramural program of the NIH
and through a grant from WCU Project (R33-10059) through the NRF and by
a grant from the Next-Generation BioGreen 21 Program (No.
PJ008191032011), Rural Development Administration, Republic of Korea.
NR 54
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PU BLACKWELL SCIENCE PUBL
PI OXFORD
PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND
SN 0077-8923
BN 978-1-57331-842-6
J9 ANN NY ACAD SCI
JI Ann.NY Acad.Sci.
PY 2011
VL 1229
BP 29
EP 37
DI 10.1111/j.1749-6632.2011.06100.x
PG 9
WC Endocrinology & Metabolism; Multidisciplinary Sciences; Nutrition &
Dietetics
SC Endocrinology & Metabolism; Science & Technology - Other Topics;
Nutrition & Dietetics
GA BWJ49
UT WOS:000294027800006
PM 21793836
ER
PT J
AU Boyce, JA
Assa'ad, A
Burks, AW
Jones, SM
Sampson, HA
Wood, RA
Plaut, M
Cooper, SF
Fenton, MJ
Arshad, SH
Bahna, SL
Beck, LA
Byrd-Bredbenner, C
Camargo, CA
Eichenfield, L
Furuta, GT
Hanifin, JM
Jones, C
Kraft, M
Levy, BD
Lieberman, P
Luccioli, S
McCall, KM
Schneider, LC
Simon, RA
Simons, FER
Teach, SJ
Yawn, BP
Schwaninger, JM
AF Boyce, Joshua A.
Assa'ad, Amal
Burks, A. Wesley
Jones, Stacie M.
Sampson, Hugh A.
Wood, Robert A.
Plaut, Marshall
Cooper, Susan F.
Fenton, Matthew J.
Arshad, S. Hasan
Bahna, Sami L.
Beck, Lisa A.
Byrd-Bredbenner, Carol
Camargo, Carlos A., Jr.
Eichenfield, Lawrence
Furuta, Glenn T.
Hanifin, Jon M.
Jones, Carol
Kraft, Monica
Levy, Bruce D.
Lieberman, Phil
Luccioli, Stefano
McCall, Kathleen M.
Schneider, Lynda C.
Simon, Ronald A.
Simons, F. Estelle R.
Teach, Stephen J.
Yawn, Barbara P.
Schwaninger, Julie M.
TI Guidelines for the Diagnosis and Management of Food Allergy in the
United States: Summary of the NIAID-Sponsored Expert Panel Report
SO NUTRITION RESEARCH
LA English
DT Article
C1 [Plaut, Marshall; Cooper, Susan F.; Fenton, Matthew J.; Schwaninger, Julie M.] NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA.
[Boyce, Joshua A.] Harvard Univ, Brigham & Womens Hosp, Massachusetts Gen Hosp, Dept Med,Sch Med,Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA.
[Camargo, Carlos A., Jr.] Harvard Univ, Dept Emergency Med, Massachusetts Gen Hosp, Dept Med,Div Rheumatol Allergy & Immunol,Sch Med, Boston, MA 02115 USA.
[Levy, Bruce D.] Brigham & Womens Hosp, Pulm & Crit Med Div, Partners Asthma Ctr, Boston, MA 02115 USA.
[Assa'ad, Amal] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Div Allergy & Immunol, Cincinnati, OH USA.
[Burks, A. Wesley] Duke Univ, Med Ctr, Dept Pediat, Div Allergy & Immunol, Durham, NC 27710 USA.
[Kraft, Monica] Duke Univ, Med Ctr, Dept Med, Div Pulm Allergy & Crit Care Med, Durham, NC 27710 USA.
[Jones, Stacie M.] Univ Arkansas Med Sci, Arkansas Childrens Hosp, Dept Pediat, Div Allergy & Immunol, Little Rock, AR 72205 USA.
[Sampson, Hugh A.] Mt Sinai Sch Med, Dept Pediat, Div Allergy & Immunol, Elliot & Roslyn Jaffe Food Allergy Inst, New York, NY USA.
[Wood, Robert A.] Johns Hopkins Univ, Sch Med, Dept Pediat, Div Allergy & Immunol, Baltimore, MD 21205 USA.
[Arshad, S. Hasan] Univ Southampton, Sch Med, Southampton, Hants, England.
[Arshad, S. Hasan] St Marys Hosp, David Hide Asthma & Allergy Res Ctr, Newport, Wight, England.
[Arshad, S. Hasan] Southampton Univ Hosp NHS Trust, Southampton, Hants, England.
[Bahna, Sami L.] Louisiana State Univ, Hlth Sci Ctr, Dept Pediat, Allergy & Immunol Sect, Shreveport, LA 71105 USA.
[Beck, Lisa A.] Univ Rochester, Dept Dermatol, Med Ctr, Rochester, NY 14627 USA.
[Byrd-Bredbenner, Carol] Rutgers State Univ, Dept Nutr Sci, New Brunswick, NJ 08903 USA.
[Eichenfield, Lawrence] Rady Childrens Hosp, Div Pediat & Adolescent Dermatol, San Diego, CA USA.
[Eichenfield, Lawrence] Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA.
[Eichenfield, Lawrence] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA.
[Furuta, Glenn T.] Childrens Hosp Denver, Digest Hlth Inst, Sect Pediat Gastroenterol Hepatol & Nutr, Aurora, CO USA.
[Furuta, Glenn T.] Natl Jewish Hlth, Dept Pediat, Denver, CO USA.
[Furuta, Glenn T.] Univ Colorado Denver, Sch Med, Dept Pediat, Aurora, CO USA.
[Hanifin, Jon M.] Oregon Hlth & Sci Univ, Dept Dermatol, Portland, OR 97201 USA.
[Jones, Carol] Allergy & Asthma Network Mothers Asthmat, Mclean, VA USA.
[Lieberman, Phil] Univ Tennessee, Dept Med, Coll Med, Div Allergy & Immunol, Memphis, TN 38104 USA.
[Luccioli, Stefano] US FDA, Off Food Addit Safety, College Pk, MD USA.
[McCall, Kathleen M.] Childrens Hosp Orange Cty, Orange, CA 92668 USA.
[Schneider, Lynda C.] Childrens Hosp Boston, Div Immunol, Boston, MA USA.
[Simon, Ronald A.] Scripps Clin, Div Allergy Asthma & Immunol, San Diego, CA USA.
[Simons, F. Estelle R.] Univ Manitoba, Fac Med, Dept Pediat, Winnipeg, MB, Canada.
[Simons, F. Estelle R.] Univ Manitoba, Fac Med, Dept Child Hlth & Immunol, Winnipeg, MB, Canada.
[Teach, Stephen J.] Childrens Natl Med Ctr, Div Emergency Med, Washington, DC 20010 USA.
[Yawn, Barbara P.] Olmsted Med Ctr, Dept Res, Rochester, MN USA.
[Yawn, Barbara P.] Univ Minnesota, Sch Med, Dept Family & Community Hlth, Minneapolis, MN 55455 USA.
RP Fenton, MJ (reprint author), NIAID, Div Allergy Immunol & Transplantat, NIH, 6610 Rockledge Dr,Room 3105, Bethesda, MD 20892 USA.
EM fentonm@niaid.nih.gov
RI Byrd-Bredbenner, Carol/F-8064-2015
OI Byrd-Bredbenner, Carol/0000-0002-8010-3987
FU National Institutes of Health; GlaxoSmithKline; Food Allergy and
Anaphylaxis Network; Gerber; Mead Johnson; Dyax Corp; National Peanut
Board; Food Allergy Initiative; National Institutes of Health (Division
of Receipt and Referral, National Institute of Allergy and Infectious
Diseases, National Center for Complementary and Alternative Medicine);
Phadia AB; Genentech; National Institutes of Health (National Institute
of Allergy and Infectious Diseases); National Institute of Health
Research, UK; American Academy of Allergy, Asthma, and Immunology;
National Eczema Association; US Department of Agriculture; Canned Food
Alliance; New Jersey Department of Health and Senior Services; variety
of government agencies; Dey; Novartis; Astellas; Ferndale; Johnson
Johnson; Sinclair; Stiefel; Therapeutics Inc
FX J. A. Boyce has served on the Advisory Board of GlaxoStmithKline. He has
served as a consultant and/or speaker for Altana, GlaxoSmithKline, and
Merck. He has received funding/grant support from the National
Institutes of Health.; A. Assa'ad holds, or is listed as an inventor on,
US patent application #10/566903, entitled "Genetic markers of food
allergy." She has served as a consultant for GlaxoStmithKline and as a
speaker for the American College of Allergy, Asthma, and Immunology, the
North East Allergy Society, the Virginia Allergy Society, the New
England Allergy Society, and the American Academy of Pediatrics. Dr
Assa'ad has received funding/grant support from GlaxoSmithKline.; A. W.
Burks holds, or is listed as an inventor on, multiple US patents related
to food allergy. He owns stock in Allertein and MastCell, Inc, and is a
minority stockholder in Daimon Co Probiotics. He has served as a
consultant for ActoGeniX NV, McNeil Nutritionals, Mead Johnson, and
Novartis. He has served on the speaker's bureau for EpiPen/Dey, LP, and
has served on the data monitoring committee for Genentech. He has served
on an expert panel for Nutricia. Dr Burks has received funding/grant
support from the Food Allergy and Anaphylaxis Network, Gerber, Mead
Johnson, and the National Institutes of Health.; S. M. Jones has served
as a speaker and grant reviewer and has served on the medical advisory
committee for the Food Allergy and Anaphylaxis Network. She has received
funding/grant support from Dyax Corp, the Food Allergy and Anaphylaxis
Network, Mead Johnson, the National Peanut Board, and the National
Institutes of Health.; H. A. Sampson holds, or is listed as an inventor
on, multiple US patents related to food allergy. He owns stock in
Allertein Therapeutics. He is the immediate past president of the
American Academy of Allergy, Asthma, and Immunology. He has served as a
consultant for Allertein Therapeutics, the American Academy of Allergy,
Asthma, and Immunology, the Food Allergy Initiative, and Schering
Plough. He has received funding/grant support for research projects from
the Food Allergy Initiative, the National Institutes of Health (Division
of Receipt and Referral, National Institute of Allergy and Infectious
Diseases, National Center for Complementary and Alternative Medicine),
and Phadia AB. He is a co-owner of Herbal Spring, LLC.; R. A. Wood has
served as a speaker/advisory board member for GlaxoSmithKline, Merck,
and Dey. He has received funding/grant support from Genentech and the
National Institutes of Health (National Institute of Allergy and
Infectious Diseases).; S. H. Arshad has received funding/grant support
from the National Institutes of Health and the National Institute of
Health Research, UK.; S. L. Bahna has received funding/grant support
from Genentech.; L. A. Beck has received funding/grant support from the
American Academy of Allergy, Asthma, and Immunology, the National Eczema
Association, and the National Institutes of Health.; C. Byrd-Bredbenner
owns stock in Johnson & Johnson. She has received funding/grant support
from the US Department of Agriculture, the Canned Food Alliance, and the
New Jersey Department of Health and Senior Services.; C. A. Camargo Jr
has consulted for Dey and Novartis. He has received funding/grant
support from a variety of government agencies and not-for-profit
research foundations, as well as Dey and Novartis.; L. Eichenfield has
received funding/grant support from a variety of not-for-profit
foundations, as well as Astellas, Ferndale, Johnson & Johnson, Novartis,
Sinclair, Stiefel, and Therapeutics Inc.
NR 1
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U2 8
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0271-5317
J9 NUTR RES
JI Nutr. Res.
PD JAN
PY 2011
VL 31
IS 1
BP 61
EP 75
DI 10.1016/j.nutres.2011.01.001
PG 15
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 724ZB
UT WOS:000287613900010
PM 21310308
ER
PT S
AU Heindel, JJ
AF Heindel, Jerrold J.
BE Lustig, RH
TI The Obesogen Hypothesis of Obesity: Overview and Human Evidence
SO OBESITY BEFORE BIRTH: MATERNAL AND PRENATAL INFLUENCES ON THE OFFSPRING
SE Endocrine Updates
LA English
DT Article; Book Chapter
ID MATERNAL SMOKING; INTRAUTERINE EXPOSURE; DEVELOPMENTAL ORIGINS;
METABOLIC SYNDROME; CHILD OVERWEIGHT; PREGNANCY; HEALTH; FETAL;
FRUCTOSE; DISEASE
C1 Natl Inst Environm Hlth Sci, Div Extramural Res & Training, Res Triangle Pk, NC USA.
RP Heindel, JJ (reprint author), Natl Inst Environm Hlth Sci, Div Extramural Res & Training, Res Triangle Pk, NC USA.
EM heindelj@niehs.nih.gov
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U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES
SN 1566-0729
BN 978-1-4419-7033-6
J9 ENDOCR UPDAT
PY 2011
BP 355
EP 365
DI 10.1007/978-1-4419-7034-3_17
D2 10.1007/978-1-4419-7034-3
PG 11
WC Endocrinology & Metabolism; Obstetrics & Gynecology
SC Endocrinology & Metabolism; Obstetrics & Gynecology
GA BRK21
UT WOS:000282900300017
ER
PT J
AU Harper, M
Zheng, SL
Thom, E
Klebanoff, MA
Thorp, J
Sorokin, Y
Varner, MW
Iams, JD
Dinsmoor, M
Mercer, BM
Rouse, DJ
Ramin, SM
Anderson, GD
AF Harper, Margaret
Zheng, S. Lilly
Thom, Elizabeth
Klebanoff, Mark A.
Thorp, John, Jr.
Sorokin, Yoram
Varner, Michael W.
Iams, Jay D.
Dinsmoor, Mara
Mercer, Brian M.
Rouse, Dwight J.
Ramin, Susan M.
Anderson, Garland D.
CA Eunice Kennedy Shriver Natl Inst
TI Cytokine Gene Polymorphisms and Length of Gestation
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID NECROSIS-FACTOR-ALPHA; SPONTANEOUS PRETERM DELIVERY; PROMOTER
POLYMORPHISM; INTRAUTERINE INFECTION; BIRTH; ASSOCIATION; DISEASE;
CHORIOAMNIONITIS; PARTURITION; RECEPTOR
AB OBJECTIVE: To estimate whether there is an association between length of gestation and gene polymorphisms that effect transcription of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), or interleukin-1 beta (IL-1 beta).
METHODS: Blood for DNA analysis was collected from 834 women at high risk enrolled in a randomized, clinical trial of omega-3 fatty acid supplementation for the prevention of recurrent preterm birth. Genotyping was performed for three single nucleotide polymorphisms (SNPs), TNF-alpha -308, IL-6 -174, and IL-1 beta +3954. Women with the homozygous minor genotype were compared with women with either the heterozygous or the homozygous major genotype. Kaplan-Meier curves of gestational age at delivery and odds ratios for extreme preterm delivery were adjusted for African-American race and treatment group.
RESULTS: Women who were homozygous for the minor allele at the -308 position in the promoter region of the TNF-alpha gene had significantly shorter length of gestation than women who were either heterozygous or homozygous for the major allele (adjusted hazard ratio 1.74, 95% confidence interval [CI] 1.04-2.90, P=.03). Among women with this genotype, 20% (3/15) experienced extreme spontaneous preterm delivery (less than 28 weeks of gestation; adjusted odds ratio 7.51, 95% CI 1.84-30.72, P=.005). There was no difference in length of gestation or risk of extreme spontaneous preterm delivery by genotype for the IL-6 -174 or the IL-1 beta +3954 SNP.
CONCLUSION: Polymorphism at the -308 position in the TNF-alpha promoter region is associated with shorter gestation and an increased risk of spontaneous extreme preterm delivery.
C1 Wake Forest Univ Hlth Sci, Dept Obstet & Gynecol, Winston Salem, NC USA.
Wake Forest Univ Hlth Sci, Ctr Human Genom, Winston Salem, NC USA.
Univ N Carolina, Dept Obstet & Gynecol, Chapel Hill, NC USA.
Wayne State Univ, Detroit, MI USA.
Univ Utah, Hlth Sci Ctr, Salt Lake City, UT USA.
Ohio State Univ, Columbus, OH 43210 USA.
Northwestern Univ, Chicago, IL 60611 USA.
Case Western Reserve Univ, Metrohlth Med Ctr, Cleveland, OH USA.
Univ Alabama, Birmingham, AL USA.
Univ Texas Hlth Sci Ctr Houston, Houston, TX USA.
Univ Texas Med Branch, Galveston, TX USA.
George Washington Univ, Ctr Biostat, Washington, DC USA.
Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Harper, M (reprint author), Mt Area Hlth Educ Ctr, 900 Hendersonville Rd,Suite 206, Asheville, NC 28803 USA.
EM harper.margaret@gmail.com
RI Varner, Michael/K-9890-2013
OI Varner, Michael/0000-0001-9455-3973
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD) [HD27860, HD27917, HD40560, HD34208, HD40485,
HD21410, HD27915, HD40500, HD40512, HD40544, MO1-relative risk-000080,
HD34136, HD27869, HD40545, HD36801, HD19897]
FX Supported by grants from the Eunice Kennedy Shriver National Institute
of Child Health and Human Development (NICHD) (HD27860, HD27917,
HD40560, HD34208, HD40485, HD21410, HD27915, HD40500, HD40512, HD40544,
MO1-relative risk-000080, HD34136, HD27869, HD40545, HD36801, HD19897).
The views in this article do not necessarily represent the official
views of the NICHD or the National Institutes of Health.
NR 37
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U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD JAN
PY 2011
VL 117
IS 1
BP 125
EP 130
DI 10.1097/AOG.0b013e318202b2ef
PG 6
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 697GI
UT WOS:000285500800018
PM 21173653
ER
PT J
AU Bhatti, P
Stewart, PA
Linet, MS
Blair, A
Inskip, PD
Rajaraman, P
AF Bhatti, Parveen
Stewart, Patricia A.
Linet, Martha S.
Blair, Aaron
Inskip, Peter D.
Rajaraman, Preetha
TI Comparison of occupational exposure assessment methods in a case-control
study of lead, genetic susceptibility and risk of adult brain tumours
SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE
LA English
DT Article
ID ENVIRONMENT INTERACTION; RETROSPECTIVE EVALUATION; SAMPLE-SIZE; MATRIX;
INFORMATION; POPULATION; HISTORIES; CANCER; MODEL
AB Objectives There is great interest in evaluating gene-environment interactions with chemical exposures, but exposure assessment poses a unique challenge in case-control studies. Expert assessment of detailed work history data is usually considered the best approach, but it is a laborious and time-consuming process. We set out to determine if a less intensive method of exposure assessment (a job exposure matrix (JEM)) would produce similar results to a previous analysis that found evidence of effect modification of the association between expert-assessed lead exposure and risk of brain tumours by a single nucleotide polymorphism in the ALAD gene (rs1800435).
Methods We used data from a study of 355 patients with glioma, 151 patients with meningioma and 505 controls. Logistic regression models were used to examine associations between brain tumour risk and lead exposure and effect modification by genotype. We evaluated Cohen's kappa, sensitivity and specificity for the JEM compared to the expert-assessed exposure metrics.
Results Although effect estimates were imprecise and driven by a small number of cases, we found evidence of effect modification between lead exposure and ALAD genotype when using expert-but not JEM-derived lead exposure estimates. kappa Values indicated only modest agreement (<0.5) for the exposure metrics, with the JEM indicating high specificity (similar to 0.9) but poor sensitivity (similar to 0.5). Disagreement between the two methods was generally due to having additional information in the detailed work history.
Conclusion These results provide preliminary evidence suggesting that high quality exposure data are likely to improve the ability to detect genetic effect modification.
C1 [Bhatti, Parveen] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Div Publ Hlth Sci, Seattle, WA 98109 USA.
[Stewart, Patricia A.] Stewart Exposure Assessments LLC, Arlington, VA USA.
[Linet, Martha S.; Blair, Aaron; Inskip, Peter D.; Rajaraman, Preetha] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
RP Bhatti, P (reprint author), Fred Hutchinson Canc Res Ctr, Program Epidemiol, Div Publ Hlth Sci, POB 19024,M4-B874, Seattle, WA 98109 USA.
EM pbhatti@fhcrc.org
FU National Cancer Institute, National Institutes of Health, Department of
Health and Human Services [N01-CO-12400]
FX This study was funded under contract N01-CO-12400 from the Intramural
Research Program of the National Cancer Institute, National Institutes
of Health, Department of Health and Human Services.
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PU B M J 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 JAN
PY 2011
VL 68
IS 1
BP 4
EP 9
DI 10.1136/oem.2009.048132
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 692VE
UT WOS:000285182900003
PM 20798009
ER
PT J
AU Dwyer, J
Le Guelte, A
Moya, EMG
Sumbal, M
Carlotti, A
Douguet, L
Gutkind, JS
Grange, PA
Dupin, N
Gavard, J
AF Dwyer, J.
Le Guelte, A.
Moya, E. M. Galan
Sumbal, M.
Carlotti, A.
Douguet, L.
Gutkind, J. S.
Grange, P. A.
Dupin, N.
Gavard, J.
TI Remodeling of VE-cadherin junctions by the human herpes virus 8
G-protein coupled receptor
SO ONCOGENE
LA English
DT Article
DE cell junctions; permeability; rac; PI(3)K; VE-cadherin; kaposi sarcoma
ID SARCOMA-ASSOCIATED-HERPESVIRUS; KAPOSIS-SARCOMA; ENDOTHELIAL
PERMEABILITY; VASCULAR-PERMEABILITY; PARACRINE NEOPLASIA; ADHERENS
JUNCTIONS; GENE-EXPRESSION; GROWTH-FACTOR; CELL; VGPCR
AB Kaposi Sarcoma (KS) are opportunistic tumors, associated with human herpes virus 8 (HHV8) infection. KS development is highly favored by immune-depression and remains the second most frequent tumor in acquired immune deficiency syndrome patients. Although it has been shown that experimental expression of the HHV8 G-protein-coupled receptor (vGPCR) in the endothelial compartment is alone sufficient to recapitulate the formation and progression of KS-like lesions, its functional effects on endothelial homeostasis are not fully understood. Here we show that vGPCR expression in endothelial cells induces an increase in paracellular permeability both in vivo and in vitro. By using pharmacological inhibitors and small interference RNA-based knockdown, we demonstrate an essential role for the PI(3)Kinase-gamma/Rac nexus in vGPCR-mediated permeability. This was further accompanied by dramatic remodeling of VE-cadherin-dependent cell-cell junctions. Importantly, this in vitro vGPCR-initiated signaling signature was observed in a large panel of human KS. Altogether, our results support the hypothesis that endothelial vGPCR signaling is co-opted in KS, and unveil new key cellular targets for therapeutic intervention. Oncogene (2011) 30, 190-200; doi: 10.1038/onc.2010.411; published online 6 September 2010
C1 [Dwyer, J.; Le Guelte, A.; Moya, E. M. Galan; Sumbal, M.; Douguet, L.; Gavard, J.] Univ Paris 05, Inst Cochin, CNRS UMR 8104, INSERM,U1016, F-75014 Paris, France.
[Carlotti, A.] Univ Paris 05, Grp Hosp Cochin Port Royal, AP HP, Serv Anat & Cytol Pathol,Fac Med, F-75014 Paris, France.
[Gutkind, J. S.] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA.
[Grange, P. A.; Dupin, N.] Univ Paris 05, Lab Rech Dermatol, EA 1833, Fac Med, F-75014 Paris, France.
[Dupin, N.] Univ Paris 05, Grp Hosp Cochin Port Royal Pavillon Tarnier, AP HP, Serv Dermatol,Fac Med, F-75014 Paris, France.
RP Gavard, J (reprint author), Univ Paris 05, Inst Cochin, CNRS UMR 8104, INSERM,U1016, 22 Rue Mechain,Rm 306, F-75014 Paris, France.
EM julie.gavard@inserm.fr
RI Gutkind, J. Silvio/A-1053-2009; Gavard, Julie/I-5487-2012;
OI Gavard, Julie/0000-0002-7985-9007; Galan-Moya, Eva M/0000-0001-5758-7592
FU Ligue Nationale contre le Cancer, comite de Paris; European Community
[PIRG04-GA-2008-239126]; Fondation pour la Recherche Medicale;
Association pour la Recherche sur le Cancer
FX We would like to thank N. Bidere (Inserm U1014, Universite Paris-Sud,
Hopital Paul Brousse, Villejuif, France) for helpful discussions and
comments, A Schmitt (Institut Cochin, Paris, France) for technical help
on electron microscopy experiments, Anne Audebourg and Brigitte Radenen
(Service d'Anatomie et de Cytologie Pathologique, Hopital Cochin, Paris,
France) for technical help on histological staining, and Nina Feinberg
(OPCB, NIDCR, NIH, Bethesda, MD, USA) for technical help on the initial
project. This research was funded by Ligue Nationale contre le Cancer,
comite de Paris and by a Marie Curie International Reintegration Grant
within the 7th European Community Framework Programme
(PIRG04-GA-2008-239126). JD is supported by a post-doctoral fellowship
from Fondation pour la Recherche Medicale, ALG by the PhD program from
Universite Paris 5 and EMGM by a post-doctoral fellowship from
Association pour la Recherche sur le Cancer.
NR 38
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U1 0
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PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD JAN
PY 2011
VL 30
IS 2
BP 190
EP 200
DI 10.1038/onc.2010.411
PG 11
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 709LG
UT WOS:000286438900007
PM 20818438
ER
PT J
AU Park, HD
Lee, Y
Oh, YK
Jung, JG
Park, YW
Myung, K
Kim, KH
Koh, SS
Lim, DS
AF Park, H. D.
Lee, Y.
Oh, Y. K.
Jung, J. G.
Park, Y. W.
Myung, K.
Kim, K-H
Koh, S. S.
Lim, D-S
TI Pancreatic adenocarcinoma upregulated factor promotes metastasis by
regulating TLR/CXCR4 activation
SO ONCOGENE
LA English
DT Article
DE PAUF; TLR; CXCR4; TPL2; ERK; NF-kappa B
ID TOLL-LIKE RECEPTORS; TUMOR-GROWTH; CARBOHYDRATE SPECIFICITIES;
STRUCTURAL BASIS; BINDING LECTINS; CANCER-CELLS; ANGIOGENESIS;
LIPOPOLYSACCHARIDE; INFLAMMATION; PROGRESSION
AB Pancreatic adenocarcinoma upregulated factor (PAUF) is overproduced in certain types of cancer. However, little is known of the tumorigenic function of PAUF. In this study, we report the X-ray crystal structure of PAUF and reveal that PAUF is a mammalian lectin normally found in plant lectins. We also identify PAUF as an endogenous ligand of Toll-like receptor 2 (TLR2) and TLR4 by screening extracellular domain receptor pools. We further confirmed the specificity of the PAUF-TLR2 interaction. PAUF induces extracellular signal-regulated kinase (ERK) phosphorylation and activates the IKK-beta-mediated TPL2/MEK/ERK signaling pathway through TLR2. In agreement with the result of TLR2-mediated ERK activation by PAUF, PAUF induces increased expression of the protumorigenic cytokines RANTES and MIF in THP-1 cells. However, PAUF does not fully activate I kappa-B-alpha signaling pathways in THP-1 cells, and fails to translocate the p65 subunit of the nuclear factor-kappa B (NF-kappa B) complex into the nucleus, resulting in no NF-kappa B activation. Surprisingly, we found that PAUF also associated with the CXC chemokine receptor (CXCR4)-TLR2 complex and inhibited CXCR4-dependent, TLR2-mediated NF-kappa B activation. Together, these findings suggest that the new cancer-associated ligand, PAUF, may activate TLR-mediated ERK signaling to produce the protumorigenic cytokines, but inhibits TLR-mediated NF-kappa B signaling, thereby facilitating tumor growth and escape from innate immune surveillance. Oncogene (2011) 30, 201-211; doi:10.1038/onc.2010.401; published online 30 August 2010
C1 [Lee, Y.; Jung, J. G.; Park, Y. W.; Kim, K-H; Koh, S. S.] Korea Res Inst Biosci & Biotechnol, Therapeut Antibody Res Ctr, Taejon, South Korea.
[Park, H. D.; Lee, Y.; Lim, D-S] Natl Creat Res Initiat Ctr Cell Div & Differentia, Dept Biol Sci, Taejon, South Korea.
[Park, H. D.; Oh, Y. K.] LG Life Sci, Dept Pharmacol, Taejon, South Korea.
[Myung, K.] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Koh, SS (reprint author), Korea Res Inst Biosci & Biotechnol, Therapeut Antibody Res Ctr, Taejon, South Korea.
EM sskoh@kribb.re.kr; daesiklim@kaist.ac.kr
RI Lim, Dae-Sik/C-1599-2011
OI Lim, Dae-Sik/0000-0003-2356-7555
FU National Creative Research Initiative Center; World Class University
(WCU); Ministry of Education, Science and Technology in Korea
FX This study was supported by grants from the National Creative Research
Initiative Center Program, World Class University (WCU) program and the
21st Century Frontier Functional Human Genome Project of the Ministry of
Education, Science and Technology in Korea. We thank Sang Yong Hong for
technical support with the cloning work. We thank the staff of Beamline
4A at the Pohang Accelerator Laboratory, Korea, for assistance in data
collection and Dr Hyun Kyu Song of Korea University for help with MAD
data analysis.
NR 34
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PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD JAN
PY 2011
VL 30
IS 2
BP 201
EP 211
DI 10.1038/onc.2010.401
PG 11
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 709LG
UT WOS:000286438900008
PM 20802527
ER
PT J
AU DeCicco-Skinner, KL
Trovato, EL
Simmons, JK
Lepage, PK
Wiest, JS
AF DeCicco-Skinner, K. L.
Trovato, E. L.
Simmons, J. K.
Lepage, P. K.
Wiest, J. S.
TI Loss of tumor progression locus 2 (tpl2) enhances tumorigenesis and
inflammation in two-stage skin carcinogenesis
SO ONCOGENE
LA English
DT Article
DE Tpl2; skin cancer; inflammation; MAP3K8; NF-kappa B
ID NF-KAPPA-B; PROTEIN-KINASE-C; NF-KAPPA-B1 P105; MOUSE SKIN; SIGNALING
PATHWAYS; CANCER DEVELOPMENT; TRANSGENIC MICE; T-CELLS; IN-VIVO;
ACTIVATION
AB Tumor progression locus 2 (Tpl2) is a serine/threonine kinase in the mitogen-activated protein kinase signal transduction cascade known to regulate inflammatory pathways. Previously identified as an oncogene, its mutation or overexpression is reported in a variety of human cancers. To address its role in skin carcinogenesis, Tpl2(-/-) or wild-type (WT) C57BL/6 mice were subjected to a two-stage dimethylbenzanthracene/12-O-tetradecanoylphorbol- 13-acetate (TPA) mouse skin carcinogenesis model. Tpl2(-/-) mice developed a significantly higher incidence of tumors (80%) than WT mice (17%), as well as a reduced tumor latency and a significantly higher number of total tumors (113 vs 6). Moreover, Tpl2(-/-) mice treated with TPA experienced significantly higher nuclear factor kappaB (NF-kappa B) activation, edema, infiltrating neutrophils and production of proinflammatory cytokines than did WT mice. We investigated the role of the p38, JNK, MEK and NF-kappa B signaling pathways both in vitro and in vivo in WT and Tpl2(-/-) mice by using inhibitors for each of these pathways. We confirmed that the proinflammatory effect in Tpl2(-/-) mice was due to heightened activity of the NF-kappa B pathway. These studies indicate that Tpl2 may serve more as a tumor suppressor than as an oncogene in chemically induced skin carcinogenesis, with its absence contributing to both tumorigenesis and inflammation. Oncogene (2011) 30, 389-397; doi: 10.1038/onc.2010.447; published online 11 October 2010
C1 [DeCicco-Skinner, K. L.; Trovato, E. L.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Trovato, E. L.; Simmons, J. K.; Lepage, P. K.; Wiest, J. S.] American Univ, Dept Biol, Washington, DC 20016 USA.
RP Wiest, JS (reprint author), NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, 37 Convent Dr, Bethesda, MD 20892 USA.
EM wiestj@mail.nih.gov
FU NCI/NIH
FX We thank Dr Jyotsna Pandey for her assistance with confocal microscopy.
This work was supported by the NCI/NIH Intramural Research Program.
NR 44
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U1 2
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD JAN
PY 2011
VL 30
IS 4
BP 389
EP 397
DI 10.1038/onc.2010.447
PG 9
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 711WH
UT WOS:000286621600002
PM 20935675
ER
PT J
AU Schug, TT
AF Schug, Thaddeus T.
TI Targeting Transcription Through Inhibition of TBP
SO ONCOTARGET
LA English
DT Editorial Material
ID RNA-POLYMERASE-II
C1 NIEHS, Div Extramural Res & Training, Cellular Organ & Syst Pathobiol Branch, Res Triangle Pk, NC 27709 USA.
RP Schug, TT (reprint author), NIEHS, Div Extramural Res & Training, Cellular Organ & Syst Pathobiol Branch, POB 12233, Res Triangle Pk, NC 27709 USA.
EM Schugt@niehs.nih.gov
NR 9
TC 1
Z9 1
U1 0
U2 0
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD JAN-FEB
PY 2011
VL 2
IS 1-2
BP 5
EP 7
PG 3
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 802JT
UT WOS:000293507100002
PM 21378415
ER
PT J
AU Charles, BA
Conley, YP
Chen, GJ
Miller, RG
Dorman, JS
Gorin, MB
Ferrell, RE
Sereika, SM
Rotimi, CN
Orchard, TJ
AF Charles, Bashira A.
Conley, Yvette P.
Chen, Guanjie
Miller, Rachel G.
Dorman, Janice S.
Gorin, Michael B.
Ferrell, Robert E.
Sereika, Susan M.
Rotimi, Charles N.
Orchard, Trevor J.
TI Variants of the Adenosine A(2A) Receptor Gene Are Protective against
Proliferative Diabetic Retinopathy in Patients with Type 1 Diabetes
SO OPHTHALMIC RESEARCH
LA English
DT Article
DE Diabetes; Diabetic retinopathy; Single nucleotide polymorphism;
Adenosine receptor
ID ENDOTHELIAL GROWTH-FACTOR; NON-HISPANIC WHITES; PITTSBURGH EPIDEMIOLOGY;
ADVANCED GLYCATION; FACTOR EXPRESSION; COMPLICATIONS; ACTIVATION; CELLS;
MELLITUS; RISK
AB Aims: The adenosine A(2A) receptor (ADORA(2A)) may ameliorate deleterious physiologic effects associated with tissue injury in individuals with diabetes. We explored associations between variants of the ADORA(2A) gene and proliferative diabetic retinopathy (PDR) in a cohort of patients with type 1 diabetes (T1D). Methods: The participants were from the Pittsburgh Epidemiology of Diabetes Complications prospective study of childhood-onset T1D. Stereoscopic photographs of the retinal fundus taken at baseline, then biennially, for 10 years were used to define PDR according to the modified Airlie House system. Two tagging single nucleotide polymorphisms (tSNPs; rs2236624-C/T and rs4822489-G/T) in the ADORA(2A) gene were selected using the HapMap (haplotype map) reference database. Results: A significant association was observed between SNP rs2236624 and PDR in the recessive genetic model. Participants homozygous for the T allele displayed a decreased risk of developing prevalent PDR (odds ratio, OR = 0.36; p = 0.04) and incident PDR (hazard ratio = 0.156; p = 0.009), and for all cases of PDR combined (OR = 0.23; p = 0.001). The protective effect of T allele homozygosity remained after adjusting for covariates. Similarly, for SNP rs4822489, an association between PDR and T allele homozygosity was observed following covariate adjustment (OR = 0.55; 95% CI: 0.31-0.92; p = 0.04). Conclusion: Genetic variants of ADORA(2A) offer statistically significant protection against PDR development in patients with T1D. Copyright (C) 2010 S. Karger AG, Basel
C1 [Charles, Bashira A.; Chen, Guanjie; Rotimi, Charles N.] Natl Human Genome Res Inst, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA.
[Charles, Bashira A.] NINR, NIH, Bethesda, MD 20892 USA.
[Charles, Bashira A.; Conley, Yvette P.; Miller, Rachel G.; Dorman, Janice S.; Ferrell, Robert E.; Sereika, Susan M.; Orchard, Trevor J.] Univ Pittsburgh, Pittsburgh, PA USA.
[Gorin, Michael B.] Jules Stein Eye Inst, Los Angeles, CA 90024 USA.
[Gorin, Michael B.] Univ Calif Los Angeles, Los Angeles, CA USA.
RP Charles, BA (reprint author), Natl Human Genome Res Inst, Ctr Res Genom & Global Hlth, NIH, Bldg 12A,Room 4047,12 S Dr,MSC 5635, Bethesda, MD 20892 USA.
EM charlesba@mail.nih.gov
OI orchard, trevor/0000-0001-9552-3215
FU NIH/National Institute of Nursing Research [1F31NR008970-01A2]; American
Nurses Foundation; NIH/National Institute of Diabetes and Digestive and
Kidney Diseases [R01 DK034818-21]; National Human Genome Research
Institute, NIH, in the Center for Research in Genomics and Global Health
[Z01HG200362]
FX We would like to thank/acknowledge Dr. Adebowale Adeyemo, Deputy
Director, of the Center for Research on Genomics and Global Health,
National Human Genome Research Institute, National Institutes of Health
(NIH), for his contributions to the manuscript. This research was
conducted at the University of Pittsburgh and supported by grants
NIH/National Institute of Nursing Research 1F31NR008970-01A2 'Genetic
Basis of Diabetic Retinopathy', Charles B. (PI), American Nurses
Foundation 'Genes Implicated in Time to Onset and Severity of Diabetic
Retinopathy', Charles B. (PI), and NIH/National Institute of Diabetes
and Digestive and Kidney Diseases R01 DK034818-21 'Epidemiology of
Diabetes Complications, Phase II', Orchard (PI). This research was also
supported in part by the Intramural Research Program of the National
Human Genome Research Institute, NIH, in the Center for Research in
Genomics and Global Health (Z01HG200362).
NR 52
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Z9 4
U1 0
U2 4
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0030-3747
J9 OPHTHALMIC RES
JI Ophthalmic Res.
PY 2011
VL 46
IS 1
BP 1
EP 8
DI 10.1159/000317057
PG 8
WC Ophthalmology
SC Ophthalmology
GA 782TW
UT WOS:000292035800001
PM 21088442
ER
PT J
AU Zheng, C
Shinomiya, T
Goldsmith, CM
Di Pasquale, G
Baum, BJ
AF Zheng, C.
Shinomiya, T.
Goldsmith, C. M.
Di Pasquale, G.
Baum, B. J.
TI Convenient and reproducible in vivo gene transfer to mouse parotid
glands
SO ORAL DISEASES
LA English
DT Article
DE parotid; gene transfer; adenoviral vector; mouse
ID ACID-ALPHA-GLUCOSIDASE; DISEASE TYPE-II; SALIVARY-GLANDS; ADENOVIRAL
VECTOR; KNOCKOUT MICE; EXPRESSION; THERAPEUTICS; SECRETION; RESPONSES;
DELIVERY
AB Objectives:
Published studies of gene transfer to mouse salivary glands have not employed the parotid glands. Parotid glands are the likely target tissue for most clinical applications of salivary gene transfer. The purpose of the present study was to develop a convenient and reproducible method of retroductal gene transfer to mouse parotid glands.
Methods:
The volume for vector delivery was assessed by infusion of Toluidine Blue into Stensen's ducts of Balb/c mice after direct intraoral cannulation. Recombinant, serotype 5 adenoviral vectors, encoding either firefly luciferase or human erythropoietin (hEpo), were constructed and then administered to parotid glands (107 vector particles/gland). Transgene expression in vivo was measured by enzyme activity (luciferase) or an enzyme-linked immunosorbent assay (hEpo). Vector biodistribution was measured by real-time quantitative (Q) PCR.
Results:
The chosen volume for mouse parotid vector delivery was 20 mu L. Little vector was detected outside of the targeted glands, with both QPCR and luciferase assays. Transgene expression was readily detected in glands (luciferase, hEpo), and serum and saliva (hEpo). Most secreted hEpo was detected in saliva.
Conclusion:
These studies show that mouse parotid glands can be conveniently and reproducibly targeted for gene transfer, and should be useful for pre-clinical studies with many murine disease models.
C1 [Zheng, C.; Shinomiya, T.; Goldsmith, C. M.; Di Pasquale, G.; Baum, B. J.] NIDCR, MPTB, NIH, Bethesda, MD 20892 USA.
RP Baum, BJ (reprint author), NIDCR, MPTB, NIH, Bldg 10,Room 1N113,MSC-1190,10 Ctr Dr, Bethesda, MD 20892 USA.
EM bbaum@dir.nidcr.nih.gov
FU National Institute of Dental and Craniofacial Research
FX This research was supported by the Intramural Research Program of the
National Institute of Dental and Craniofacial Research.
NR 31
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Z9 5
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1354-523X
J9 ORAL DIS
JI Oral Dis.
PD JAN
PY 2011
VL 17
IS 1
BP 77
EP 82
DI 10.1111/j.1601-0825.2010.01707.x
PG 6
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 693UK
UT WOS:000285250700011
PM 20646229
ER
PT J
AU Telu, S
Chun, JH
Simeon, FG
Lu, SY
Pike, VW
AF Telu, Sanjay
Chun, Joong-Hyun
Simeon, Fabrice G.
Lu, Shuiyu
Pike, Victor W.
TI Syntheses of mGluR5 PET radioligands through the radiofluorination of
diaryliodonium tosylates
SO ORGANIC & BIOMOLECULAR CHEMISTRY
LA English
DT Article
ID POSITRON-EMISSION-TOMOGRAPHY; GLUTAMATE SUBTYPE-5 RECEPTORS; NEAR-UV
PHOTOINITIATOR; PAIR ELECTRON-TRANSFER; SENSITIZED PHOTOLYSIS;
DIPHENYLIODONIUM; SALTS; F-18; ION; CHEMISTRY
AB 3-Fluoro-1-((thiazol-4-yl) ethynyl) benzenes constitute an important class of high-affinity metabotropic glutamate subtype 5 receptor (mGluR5) ligands, some of which have been labeled with fluorine-18 (t(1/2) = 109.7 min), to provide radioligands for molecular imaging of brain mGluR5 in living animal and human subjects with positron emission tomography (PET). Labeling in the 3-fluoro position of such ligands can be achieved through aromatic nucleophilic substitution of a halide leaving group with [(18)F] fluoride ion when a weakly activating m-nitrile group is present, but is generally very low yielding (< 8%). Here we used a microfluidic reaction platform to show that greatly enhanced (up to 6-fold) radiochemical yields can be achieved from suitably synthesized diaryliodonium tosylate precursors. The presence of a m-nitrile or other activating group is not required. Similar conditions were adopted in a more conventional automated radiochemistry platform having a single-pot reactor, to produce mGluR5 radioligands with useful radioactivities for PET imaging.
C1 [Telu, Sanjay; Chun, Joong-Hyun; Simeon, Fabrice G.; Lu, Shuiyu; Pike, Victor W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
RP Pike, VW (reprint author), NIMH, Mol Imaging Branch, NIH, Rm B3C346A,10 Ctr Dr, Bethesda, MD 20892 USA.
EM pikev@mail.nih.gov
OI Lu, Shuiyu/0000-0003-0310-4318
FU National Institutes of Health (NIMH)
FX This research was supported by the Intramural Research Program of the
National Institutes of Health (NIMH). The authors are grateful to the
NIH Clinical Center PET Department (Chief, Dr Peter Herscovitch) for the
cyclotron production of fluorine-18.
NR 41
TC 27
Z9 27
U1 0
U2 20
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 1477-0520
J9 ORG BIOMOL CHEM
JI Org. Biomol. Chem.
PY 2011
VL 9
IS 19
BP 6629
EP 6638
DI 10.1039/c1ob05555k
PG 10
WC Chemistry, Organic
SC Chemistry
GA 818AL
UT WOS:000294720600028
PM 21845279
ER
PT J
AU Choi, MJ
Chandra, G
Lee, HW
Hou, X
Choi, WJ
Phan, K
Jacobson, KA
Jeong, LS
AF Choi, Mun Ju
Chandra, Girish
Lee, Hyuk Woo
Hou, Xiyan
Choi, Won Jun
Khai Phan
Jacobson, Kenneth A.
Jeong, Lak Shin
TI Regio- and stereoselective synthesis of truncated 3
'-aminocarbanucleosides and their binding affinity at the A(3) adenosine
receptor
SO ORGANIC & BIOMOLECULAR CHEMISTRY
LA English
DT Article
ID L-CYCLOPENTENONE DERIVATIVES; CELL-CYCLE ARREST; CL-IB-MECA; CARBOCYCLIC
NUCLEOSIDES; AGONIST; INHIBITION; SULFITES; RADIOLIGAND; APOPTOSIS;
SULFATES
AB The stereoselective synthesis of truncated 3'-aminocarbanucleosides 4a-d via a stereo- and regioselective conversion of a diol 9 to bromoacetate 11a and their binding affinity towards the human A(3) adenosine receptor are described.
C1 [Choi, Mun Ju; Chandra, Girish; Lee, Hyuk Woo; Hou, Xiyan; Choi, Won Jun; Jeong, Lak Shin] Ewha Womans Univ, Coll Pharm, Med Chem Lab, Seoul 120750, South Korea.
[Choi, Mun Ju; Chandra, Girish; Lee, Hyuk Woo; Hou, Xiyan; Choi, Won Jun; Jeong, Lak Shin] Ewha Womans Univ, Dept Bioinspired Sci, Seoul 120750, South Korea.
[Choi, Won Jun] Dongguk Univ, Coll Pharm, Kyonggi Do 410774, South Korea.
[Khai Phan; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Jeong, LS (reprint author), Ewha Womans Univ, Coll Pharm, Med Chem Lab, Seoul 120750, South Korea.
EM lakjeong@ewha.ac.kr
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
FU Korea Research Foundation [NRF-2008-314-E00304, R31-2008-000-10010-0,
R15-2006-020]; NIDDK
FX This work was supported by the grant from the Korea Research Foundation
(NRF-2008-314-E00304, R31-2008-000-10010-0, and R15-2006-020) and the
NIDDK Intramural Research program.
NR 34
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U1 0
U2 1
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 1477-0520
J9 ORG BIOMOL CHEM
JI Org. Biomol. Chem.
PY 2011
VL 9
IS 20
BP 6955
EP 6962
DI 10.1039/c1ob05853c
PG 8
WC Chemistry, Organic
SC Chemistry
GA 833MP
UT WOS:000295889900016
PM 21860878
ER
PT J
AU Cappola, AR
Hawkes, WG
Blocher, N
Yu-Yahiro, J
Orwig, D
Fredman, L
Miller, RR
Guralnik, JM
Magaziner, J
AF Cappola, A. R.
Hawkes, W. G.
Blocher, N.
Yu-Yahiro, J.
Orwig, D.
Fredman, L.
Miller, R. R.
Guralnik, J. M.
Magaziner, J.
TI The hormonal profile of hip fracture female patients differs from
community-dwelling peers over a 1-year follow-up period
SO OSTEOPOROSIS INTERNATIONAL
LA English
DT Article
DE 1,25; Dihydroxyvitamin D; Elderly; Hip fracture; Hormones; IGF-1;
Osteocalcin; PTH; Women
ID VITAMIN-D-DEFICIENCY; FEMORAL-NECK OSTEOPOROSIS; BONE-MINERAL DENSITY;
IGF-I LEVELS; ELDERLY-WOMEN; POSTMENOPAUSAL WOMEN; OLDER WOMEN;
CALCIOTROPIC HORMONES; BIOCHEMICAL MARKERS; BINDING-PROTEIN
AB Hormone levels were compared over a 1-year period between elderly women who had sustained a hip fracture and women of similar age and functional ability. Our study suggests progressive hormonal changes that may contribute to severe bone loss during the year following hip fracture.
Alterations in hormones affecting the musculoskeletal system may increase risk of hip fracture or poor post-fracture recovery in postmenopausal women. Most studies lack appropriate reference groups, and thus cannot assess the extent to which these alterations are attributable to hip fracture.
Women aged a parts per thousand yen65 years hospitalized for an acute hip fracture (Baltimore Hip Studies, BHS-3; n = 162) were age-matched to 324 women enrolled in the Women's Health and Aging Study I, a Baltimore-based cohort with similar functional status to the pre-fracture status of BHS-3 women. Both studies enrolled participants from 1992 to 1995. Insulin-like growth hormone-1 (IGF-1), parathyroid hormone (PTH), 1,25 dihydroxyvitamin D [1,25(OH)2D], and osteocalcin were evaluated at baseline and 2, 6, and 12 months post-fracture, and at baseline and 12 months in the comparison group. Between-group differences in trajectories of each hormone were examined.
Baseline mean IGF-1 levels were significantly lower in hip fracture patients than the comparison group (75.0 vs. 110.5 mu g/dL; p < 0.001). Levels increased by 2 months post-fracture, but remained significantly lower than those in the comparison group throughout the 12-month follow-up (p < 0.01). Levels of PTH and osteocalcin were similar between groups at baseline, but rose during the year post-fracture to significantly differ from the comparison women (p < 0.001). 1,25(OH)2D levels did not differ between the hip fracture and comparison women at any time.
Older women who have sustained a hip fracture have progressive changes in hormonal milieu that exceed those of women of similar health status during the year following fracture.
C1 [Cappola, A. R.] Univ Penn Sch Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA.
[Hawkes, W. G.; Orwig, D.; Miller, R. R.; Magaziner, J.] Univ Maryland, Dept Epidemiol & Prevent Med, Div Gerontol, Baltimore, MD 21201 USA.
[Blocher, N.] Albert Einstein Med Ctr, Div Endocrinol, Philadelphia, PA 19141 USA.
[Yu-Yahiro, J.] Union Mem Hosp, Dept Orthopaed Surg, Baltimore, MD USA.
[Fredman, L.] Boston Univ Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Guralnik, J. M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
RP Cappola, AR (reprint author), Univ Penn Sch Med, Div Endocrinol Diabet & Metab, 764 CRB,415 Curie Blvd, Philadelphia, PA 19104 USA.
EM acappola@mail.med.upenn.edu
FU National Institute on Aging [K23 AG19161, R37 AG009901, P30 AG028747,
N01-AG-1-2112, R37-AG19905]; National Institute on Aging, National
Institutes of Health
FX This work was supported by the National Institute on Aging K23 AG19161,
R37 AG009901, P30 AG028747, contract N01-AG-1-2112, R37-AG19905, and in
part by the Intramural Research Program, National Institute on Aging,
National Institutes of Health.
NR 28
TC 1
Z9 1
U1 0
U2 2
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 JAN
PY 2011
VL 22
IS 1
BP 339
EP 344
DI 10.1007/s00198-010-1187-4
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 703TC
UT WOS:000286003200040
PM 20204599
ER
PT S
AU Aid, S
Choi, SH
Toscano, CD
Bosetti, F
AF Aid, Saba
Choi, Sang-Ho
Toscano, Christopher D.
Bosetti, Francesca
BE Gadoth, N
Gobel, HH
TI Distinct Roles of Cyclooxygenase-1 and Cyclooxygenase-2 in Inflammatory
and Excitotoxic Brain Injury
SO OXIDATIVE STRESS AND FREE RADICAL DAMAGE IN NEUROLOGY
SE Oxidative Stress in Applied Basic Research and Clinical Practice
LA English
DT Article; Book Chapter
DE Cyclooxygenase; Arachidonic acid; Inflammation; Excitotoxicity;
Nonsteroidal antiinflammatory drugs; Alzheimer's disease; Prostaglandins
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; INDUCED OXIDATIVE DAMAGE;
PASSIVE-AVOIDANCE TASK; CENTRAL-NERVOUS-SYSTEM; NEURONAL CELL-DEATH;
BARRIER IN-VITRO; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; RAT
HIPPOCAMPUS; INDUCIBLE CYCLOOXYGENASE
AB The cyclooxygenases COX-1 and COX-2 metabolize arachidonic acid to prostaglandins (PGs) and thromboxanes and are thought to play a role in neuroinflammation and excitotoxicity, which are important components in the progression of neurodegenerative diseases. However, the exact role of each isoform in these processes remains unclear. This chapter reviews preclinical and clinical data on COX-1 and COX-2 inhibition in the neuroinflammatory and excitotoxic processes. Potential implications for clinical use in patients suffering from neurodegenerative disorders with a marked inflammatory component, such as Alzheimer's disease, are discussed.
C1 [Bosetti, Francesca] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
RP Bosetti, F (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
EM frances@mail.nih.gov
NR 121
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES
SN 2197-7224
BN 978-1-60327-513-2
J9 OXID STRESS APPL BAS
JI Oxid. Stress Appl. Basic Res. Clin. Pract.
PY 2011
BP 119
EP 136
DI 10.1007/978-1-60327-514-9_8
D2 10.1007/978-1-60327-514-9
PG 18
WC Biochemical Research Methods; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA BSM94
UT WOS:000284978600008
ER
PT J
AU Grobman, WA
Lai, YL
Landon, MB
Spong, CY
Rouse, DJ
Varner, MW
Caritis, SN
Harper, M
Wapner, RJ
Sorokin, Y
AF Grobman, William A.
Lai, Yinglei
Landon, Mark B.
Spong, Catherine Y.
Rouse, Dwight J.
Varner, Michael W.
Caritis, Steve N.
Harper, Margaret
Wapner, Ronald J.
Sorokin, Yoram
CA Eunice Kennedy Shriver Natl Inst C
TI The change in the rate of vaginal birth after caesarean section
SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY
LA English
DT Article
DE prior caesarean section; trial of birth; time trend; vaginal birth after
caesarean
ID DELIVERY; TRIAL; LABOR; TRENDS; RISK
AB P>Grobman WA, Lai Y, Landon MB, Spong CY, Rouse DJ, Varner MW, Caritis SN, Harper M, Wapner RJ, Sorokin Y. The change in the rate of vaginal birth after caesarean section. Paediatric and Perinatal Epidemiology 2010.
The objective of this study was to determine whether, and to what degree, the change in the vaginal birth after caesarean section (VBAC) rate is due to a change in the characteristics of the obstetric population, the undertaking of a trial of labour (TOL), or the tendency to abandon a TOL once it has been initiated. All women with one prior low transverse caesarean section (CS) and a vertex singleton gestation at term were identified in a registry of CS deliveries occurring at eight academic centres during a 4-year period (1999-2002). Women were classified by their predicted chance of VBAC and year-to-year differences were analysed. Of the 9643 women who met criteria for analysis, 5334 (55.3%) underwent a TOL. From 1999 to 2002, the VBAC rate underwent a steady decline: 51.8% to 45.1% to 37.4% to 29.8% (P < 0.001). Although there were some changes in the characteristics of the population that predispose to successful VBAC, as well as some reduction in the chance that a VBAC is successful once a TOL is undertaken, the most pervasive reason for this decline was that women became increasingly likely to forego a TOL, regardless of their likelihood of vaginal delivery. Based on these results, it appears that the change over time in the VBAC rate is multifactorial, although the greatest change has been a decrease in the frequency with which women undertake a TOL, and this change is observed in all categories of the chance of a successful TOL.
C1 [Grobman, William A.] Northwestern Univ, Dept Obstet, Chicago, IL 60611 USA.
[Grobman, William A.] Northwestern Univ, Dept Gynecol, Chicago, IL 60611 USA.
[Landon, Mark B.] Ohio State Univ, Columbus, OH 43210 USA.
[Rouse, Dwight J.] Univ Alabama, Birmingham, AL USA.
[Varner, Michael W.] Univ Utah, Salt Lake City, UT USA.
[Caritis, Steve N.] Univ Pittsburgh, Pittsburgh, PA USA.
[Harper, Margaret] Wake Forest Univ Hlth Sci, Winston Salem, NC USA.
[Wapner, Ronald J.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA.
[Sorokin, Yoram] Wayne State Univ, Detroit, MI USA.
[Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Lai, Yinglei] George Washington Univ, Ctr Biostat, Washington, DC USA.
RP Grobman, WA (reprint author), 250 E Super St,Suite 05-2175, Chicago, IL 60611 USA.
EM w-grobman@northwestern.edu
RI Varner, Michael/K-9890-2013
OI caritis, steve/0000-0002-2169-0712; Varner, Michael/0000-0001-9455-3973
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [HD21410, HD27860, HD27869, HD27915, HD27917, HD34116,
HD34136, HD34208, HD40512, HD36801]
FX Supported by grants from the Eunice Kennedy Shriver National Institute
of Child Health and Human Development (HD21410, HD27860, HD27869,
HD27915, HD27917, HD34116, HD34136, HD34208, HD40512 and HD36801).
NR 13
TC 14
Z9 15
U1 0
U2 4
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0269-5022
J9 PAEDIATR PERINAT EP
JI Paediatr. Perinat. Epidemiol.
PD JAN
PY 2011
VL 25
IS 1
BP 37
EP 43
DI 10.1111/j.1365-3016.2010.01169.x
PG 7
WC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
SC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
GA 691FO
UT WOS:000285065900005
PM 21133967
ER
PT J
AU Yang, PF
Chen, DY
Hu, JW
Chen, JH
Yen, CT
AF Yang, Pai-Feng
Chen, Der-Yow
Hu, James W.
Chen, Jyh-Horng
Yen, Chen-Tung
TI Functional tracing of medial nociceptive pathways using
activity-dependent manganese-enhanced MRI
SO PAIN
LA English
DT Article
DE Cingulate cortex; Intralaminar nuclei; Medial dorsal nucleus; Pain; Rat;
Thalamus
ID ANTERIOR CINGULATE CORTEX; RESONANCE-IMAGING MEMRI;
POSITRON-EMISSION-TOMOGRAPHY; MEDULLARY DORSAL-HORN; CIRCUITS IN-VIVO;
THALAMIC NUCLEI; BASAL GANGLIA; CENTRAL SENSITIZATION; RESPONSE
PROPERTIES; NEURONAL RESPONSES
AB Manganese ion (Mn(2+)) was used as a paramagnetic contrast agent in T1-weighted magnetic resonance imaging (MRI) images. They enter neural cells though voltage-gated calcium channels and are activity-dependently transported along axons and across synapses. The aim of the present study was to investigate the nociceptive medial thalamus projection in rats by activity-dependent manganese-enhanced magnetic resonance imaging (MEMRI). Rats under urethane and a-chloralose anesthesia were microinjected with manganese chloride (MnCl(2), 120 mmol/L, iontophoretically with a 5-mu A current for 15 min) into the right medial thalamus. Innocuous (at a 50-mu A intensity for 0.2 ms) or noxious (at a 5-mA intensity for 2 ms) electrical stimuli were applied through a pair of needles in the left forepaw pads once every 6 s for 5 h. Enhanced transport of Mn(2+) were found in the anterior cingulate cortex, midcingulate cortex, retrosplenial cortex, ventral medial caudate-putamen, nucleus accumbens, and amygdala in the noxious-stimulated group. Enhancements in the anterior cingulate cortex, midcingulate cortex, ventral medial caudate-putamen, nucleus accumbens, and amygdala, but not the retrosplenial cortex, were attenuated by an intraperitoneal injection of morphine (5 mg/kg and 1 mg/kg/h, intraperitoneal). These results indicate that a combination of MEMRI with activity-induced manganese-dependent contrast is useful for delineating functional connections in the pain pathway. (C) 2010 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved.
C1 [Hu, James W.; Chen, Jyh-Horng; Yen, Chen-Tung] Natl Taiwan Univ, Inst Zool, Taipei 10617, Taiwan.
[Chen, Der-Yow] Natl Inst Neurol Disorders & Stroke, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
[Yang, Pai-Feng; Chen, Jyh-Horng] Natl Taiwan Univ, Interdisciplinary MRI MRI Lab, Dept Elect Engn, Taipei 10617, Taiwan.
[Hu, James W.] Univ Toronto, Fac Dent, Toronto, ON M5G 1G6, Canada.
[Chen, Jyh-Horng; Yen, Chen-Tung] Natl Taiwan Univ, Neurobiol & Cognit Sci Ctr, Taipei 10617, Taiwan.
RP Chen, JH (reprint author), Natl Taiwan Univ, Inst Zool, 1 Roosevelt Rd,Sec 4, Taipei 10617, Taiwan.
EM jhchen@ntu.edu.tw; ctyen@ntu.edu.tw
RI Yen, Chen-Tung/F-5302-2011
OI Yen, Chen-Tung/0000-0002-0076-4487
FU National Science Council of Taiwan [NSC95-2311-B002-017-MY3]
FX We thank the interdisciplinary MRI/MRS laboratory and C. H. Hsieh of
Instrumentation Center, National Taiwan University, for MRI experiments.
This study was supported by the National Science Council of Taiwan
(NSC95-2311-B002-017-MY3).
NR 72
TC 18
Z9 19
U1 0
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-3959
J9 PAIN
JI Pain
PD JAN
PY 2011
VL 152
IS 1
BP 194
EP 203
DI 10.1016/j.pain.2010.10.027
PG 10
WC Anesthesiology; Clinical Neurology; Neurosciences
SC Anesthesiology; Neurosciences & Neurology
GA 695ZD
UT WOS:000285410800031
PM 21122994
ER
PT J
AU Kerlikowske, G
Jones, CM
LaBelle, RM
Condon, TP
AF Kerlikowske, Gil
Jones, Christopher M.
LaBelle, Regina M.
Condon, Timothy P.
TI Prescription Drug Monitoring Programs-Lack of Effectiveness or a Call to
Action?
SO PAIN MEDICINE
LA English
DT Editorial Material
ID NONMEDICAL USE
C1 [Jones, Christopher M.] US Dept HHS, US FDA, Washington, DC 20201 USA.
[Condon, Timothy P.] US Dept HHS, NIDA, Washington, DC 20201 USA.
NR 13
TC 4
Z9 4
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1526-2375
J9 PAIN MED
JI Pain Med.
PY 2011
VL 12
IS 5
BP 687
EP 689
DI 10.1111/j.1526-4637.2011.01108.x
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 762OM
UT WOS:000290489300001
PM 21481174
ER
PT J
AU Smith, WR
Ballas, SK
McCarthy, WF
Bauserman, RL
Swerdlow, PS
Steinberg, MH
Waclawiw, MA
AF Smith, Wally R.
Ballas, Samir K.
McCarthy, William F.
Bauserman, Robert L.
Swerdlow, Paul S.
Steinberg, Martin H.
Waclawiw, Myron A.
CA Investigators Multictr Study Hydro
TI The Association Between Hydroxyurea Treatment and Pain Intensity,
Analgesic Use, and Utilization in Ambulatory Sickle Cell Anemia Patients
SO PAIN MEDICINE
LA English
DT Article
DE Analgesic; Chronic Pain; Pain Management; Outcome Assessment; Randomized
Controlled Trial
ID FETAL HEMOGLOBIN; BABY HUG; HOME MANAGEMENT; RISK-FACTORS; DAILY DIARY;
DISEASE; CHILDREN; ADOLESCENTS; TRIAL; MULTICENTER
AB Background.
We compared daily pain, home analgesic use, and utilization among ambulatory adults in the randomized Multicenter Study of Hydroxyurea in Sickle Cell Anemia (MSH). We related the fetal hemoglobin (HbF) hydroxyurea response to these response variables.
Methods.
Patients rated their sickle cell pain intensity (0-9), use of analgesics, and visits for pain daily. Diaries were collected biweekly, and intensity was collapsed into single interval ratings. The interval proportions of days of analgesic use and medical visits for pain were also calculated. Group comparisons were made by intention to treat as well as by HbF change levels from baseline to 2 years of treatment (placebo and low, medium, high, or very high response).
Results.
A total of 134 (44.8%) enrollees completed 2 years of follow-up. Pain intensity correlated with analgesic use (r = 0.83, P > 0.0001) and utilization (r = 0.50, P < 0.0001). Pain intensity was lower for patients on hydroxyurea (2.51 +/- 0.062 vs 2.82 +/- 0.063 placebo, F(1,270) = 11.65, P = 0.0007). The difference, though small, appeared early and was sustained. Analgesic use and utilization were also slightly lower (analgesic use: F(1,270) = 11.97, P = 0.0006; utilization: F(1,270) = 32.0, P < 0.0001). Each was statistically significantly lower among hydroxyurea patients with higher HbF treatment responses to hydroxyurea.
Conclusions.
Hydroxyurea usage led to a small, statistically significant reduction in daily pain, analgesic use, and utilization in adults in MSH, corroborating previously shown larger reductions in crises and mortality. The degree of daily symptomatic reduction was related to the size of the HbF treatment response, further confirming HbF response as a useful laboratory correlate.
C1 [Smith, Wally R.] Virginia Commonwealth Univ, Div Qual Hlth Care, Richmond, VA 23060 USA.
[Ballas, Samir K.] Thomas Jefferson Univ, Dept Med, Cardeza Fdn, Philadelphia, PA 19107 USA.
[McCarthy, William F.] Maryland Med Res Inst, Baltimore, MD USA.
[Swerdlow, Paul S.] Karmanos Canc Inst, Div Hematol Oncol, Detroit, MI USA.
[Steinberg, Martin H.] Boston Univ, Ctr Excellence Sickle Cell Dis, Boston, MA 02215 USA.
[Waclawiw, Myron A.] NHLBI, Bethesda, MD USA.
RP Smith, WR (reprint author), Virginia Commonwealth Univ, Div Qual Hlth Care, Box 980306, Richmond, VA 23060 USA.
EM wrsmith@vcu.edu
OI Steinberg, Martin/0000-0001-8800-8020
FU National Heart, Lung, and Blood Institute [NO1-HB-67129]
FX This study was supported by National Heart, Lung, and Blood Institute
contract NO1-HB-67129.
NR 38
TC 7
Z9 7
U1 1
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1526-2375
J9 PAIN MED
JI Pain Med.
PY 2011
VL 12
IS 5
BP 697
EP 705
DI 10.1111/j.1526-4637.2011.01096.x
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 762OM
UT WOS:000290489300005
PM 21481164
ER
PT J
AU Murphy, PM
Murphy, CA
AF Murphy, Philip M.
Murphy, Carolyn A.
TI Hyperventilation as a Simple Cure for Severe Exercise-Associated Muscle
Cramping
SO PAIN MEDICINE
LA English
DT Letter
C1 [Murphy, Philip M.] NIAID, NIH, Lab Mol Immunol, Mol Signaling Sect, Bethesda, MD 20892 USA.
[Murphy, Carolyn A.] Harvard Univ, Sch Med, Brookline, MA USA.
RP Murphy, PM (reprint author), NIAID, NIH, Lab Mol Immunol, Mol Signaling Sect, 9000 Rockville Pike, Bethesda, MD 20892 USA.
FU Intramural NIH HHS
NR 4
TC 2
Z9 2
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1526-2375
J9 PAIN MED
JI Pain Med.
PY 2011
VL 12
IS 6
BP 987
EP 987
DI 10.1111/j.1526-4637.2011.01112.x
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 791GO
UT WOS:000292653300017
PM 21539699
ER
PT J
AU Reid, MC
Bennett, DA
Chen, WG
Eldadah, BA
Farrar, JT
Ferrell, B
Gallagher, RM
Hanlon, JT
Herr, K
Horn, SD
Inturrisi, CE
Lemtouni, S
Lin, YW
Michaud, K
Morrison, RS
Neogi, T
Porter, LL
Solomon, DH
Von Korff, M
Weiss, K
Witter, J
Zacharoff, KL
AF Reid, M. Cary
Bennett, David A.
Chen, Wen G.
Eldadah, Basil A.
Farrar, John T.
Ferrell, Bruce
Gallagher, Rollin M.
Hanlon, Joseph T.
Herr, Keela
Horn, Susan D.
Inturrisi, Charles E.
Lemtouni, Salma
Lin, Yu Woody
Michaud, Kaleb
Morrison, R. Sean
Neogi, Tuhina
Porter, Linda L.
Solomon, Daniel H.
Von Korff, Michael
Weiss, Karen
Witter, James
Zacharoff, Kevin L.
TI Improving the Pharmacologic Management of Pain in Older Adults:
Identifying the Research Gaps and Methods to Address Them
SO PAIN MEDICINE
LA English
DT Review
DE Analgesic Use; Chronic Noncancer Pain; Older Adults
ID CHRONIC NONCANCER PAIN; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; OBSTRUCTIVE
PULMONARY-DISEASE; PERSISTENT NONMALIGNANT PAIN; NURSING-HOME RESIDENTS;
NATIONAL-DATA-BANK; MUSCULOSKELETAL PAIN; UNITED-STATES; COGNITIVE
IMPAIRMENT; RHEUMATIC-DISEASES
AB Objective. There has been a growing recognition of the need for better pharmacologic management of chronic pain among older adults. To address this need, the National Institutes of Health Pain Consortium sponsored an "Expert Panel Discussion on the Pharmacological Management of Chronic Pain in Older Adults" conference in September 2010 to identify research gaps and strategies to address them. Specific emphasis was placed on ascertaining gaps regarding use of opioid and nonsteroidal anti-inflammatory medications because of continued uncertainties regarding their risks and benefits.
Design. Eighteen panel members provided oral presentations; each was followed by a multidisciplinary panel discussion. Meeting transcripts and panelists' slide presentations were reviewed to identify the gaps and the types of studies and research methods panelists suggested could best address them.
Results. Fifteen gaps were identified in the areas of treatment (e.g., uncertainty regarding the long-term safety and efficacy of commonly prescribed analgesics), epidemiology (e.g., lack of knowledge regarding the course of common pain syndromes), and implementation (e.g., limited understanding of optimal strategies to translate evidence-based pain treatments into practice). Analyses of data from electronic health care databases, observational cohort studies, and ongoing cohort studies (augmented with pain and other relevant outcomes measures) were felt to be practical methods for building an age-appropriate evidence base to improve the pharmacologic management of pain in later life.
Conclusion. Addressing the gaps presented in the current report was judged by the panel to have substantial potential to improve the health and wellbeing of older adults with chronic pain.
C1 [Reid, M. Cary] Weill Cornell Med Ctr, Div Geriatr & Gerontol, New York, NY 10065 USA.
[Bennett, David A.] Rush Univ, Med Ctr, Dept Neurol Sci, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA.
[Chen, Wen G.] NIA, Behav & Syst Neurosci Branch, Div Neurosci, Bethesda, MD 20892 USA.
[Eldadah, Basil A.] NIA, Div Geriatr & Clin Gerontol, Bethesda, MD 20892 USA.
[Farrar, John T.] Univ Penn, Dept Epidemiol, Philadelphia, PA 19104 USA.
[Farrar, John T.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA.
[Ferrell, Bruce] UCLA Sch Med, Div Geriatr, Los Angeles, CA USA.
Univ Penn, Sch Med, Philadelphia VA Med Ctr, Penn Pain Med Ctr, Philadelphia, PA 19104 USA.
Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA.
Univ Penn, Sch Med, Dept Anesthesiol & Crit Care, Philadelphia, PA 19104 USA.
[Gallagher, Rollin M.] Univ Pittsburgh, Dept Geriatr Med, Pittsburgh, PA USA.
[Hanlon, Joseph T.] VA Pittsburgh Hlth Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA.
[Herr, Keela] Univ Iowa, Coll Nursing, John A Hartford Ctr Geriatr Nursing Excellence, Iowa City, IA 52242 USA.
[Horn, Susan D.] Inst Clin Outcomes Res, Salt Lake City, UT USA.
[Inturrisi, Charles E.] Weill Cornell Med Coll, Dept Pharmacol, New York, NY USA.
[Lemtouni, Salma; Weiss, Karen] US FDA, Ctr Drug Evaluat & Res, Washington, DC 20204 USA.
[Lin, Yu Woody] Natl Inst Drug Abuse, Div Clin Neurosci & Behav Res, Bethesda, MD USA.
[Michaud, Kaleb] Univ Nebraska Med Ctr, Omaha, NE USA.
[Michaud, Kaleb] Natl Data Bank Rheumat Dis, Wichita, KS USA.
[Morrison, R. Sean] Mt Sinai Sch Med, Brookdale Dept Geriatr & Palliat Med, New York, NY USA.
[Neogi, Tuhina] Boston Univ, Sch Med, Sect Clin Epidemiol Res & Training Unit, Boston, MA 02118 USA.
[Neogi, Tuhina] Boston Univ, Sch Med, Rheumatol Sect, Boston, MA 02118 USA.
[Porter, Linda L.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA.
[Solomon, Daniel H.] Harvard Univ, Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Sch Med, Boston, MA 02115 USA.
[Solomon, Daniel H.] Brigham & Womens Hosp, Div Rheumatol, Boston, MA 02115 USA.
[Von Korff, Michael] Ctr Hlth Studies Grp Hlth Cooperat, Seattle, WA USA.
[Witter, James] NIAMSD, Div Skin & Rheumat Dis, Bethesda, MD 20892 USA.
[Zacharoff, Kevin L.] Inflexxion Inc, Newton, MA USA.
RP Reid, MC (reprint author), Weill Cornell Med Ctr, Div Geriatr & Gerontol, 525 E 68th St,Box 39, New York, NY 10065 USA.
EM mcr2004@med.cornell.edu
RI Inturrisi, Charles/E-7365-2013;
OI Reid, Cary/0000-0001-8117-662X; Neogi, Tuhina/0000-0002-9515-1711
FU Edward R. Roybal Center for Translational Research on Aging, NIA [P30
AG22845]; NIA [P30AG10161, R01AG15819, R01AG17917, P30AG028741,
K24AG022345, R01AG030141, R01AG034181]; National Center for Research
Resources [UL1RR024134]; National Institute of Aging [P30AG024827,
T32AG021885, K07AG033174, R01AG034056, R56AG027017, U01AG012553];
National Institute of Mental Health [R34MH082682]; National Institute of
Nursing [R01NR010135]; AHRQ [R01HS017695, R01HS018721, K12HS019461]; VA
Health Services [IIR-06-062]; National Cancer Institute [R01CA115363];
National Institute of Nursing Research [T32NR011147]; NIDA [RC2DA028928,
R01DA022557]; National Institute of Arthritis and Musculoskeletal and
Skin Diseases (NIAMS) [RC1AR058601, K23AR055127, K24AR055989]
FX The authors would like to acknowledge the participation of all the
conference attendees, who are listed in Appendix A. Dr. Reid was
supported by an Edward R. Roybal Center for Translational Research on
Aging Award (P30 AG22845) provided by the NIA. Dr. Bennett was supported
by NIA grants P30AG10161, R01AG15819, and R01AG17917. Dr. Farrar was
supported by a grant from the National Center for Research Resources
(UL1RR024134). Dr. Hanlon was supported by National Institute of Aging
grants (P30AG024827, T32AG021885, K07AG033174, R01AG034056, R56AG027017,
U01AG012553), a National Institute of Mental Health grant (R34MH082682),
a National Institute of Nursing Research grant (R01NR010135), AHRQ
grants (R01HS017695, R01HS018721, K12HS019461), and a VA Health Services
Research grant (IIR-06-062). Dr. Herr was supported by grants from the
National Cancer Institute (R01CA115363) and National Institute of
Nursing Research (T32NR011147). Drs. Horn and Inturrisi were supported
by American Recovery and Reinvestment Act (ARRA) grant RC2DA028928 from
NIDA. Dr. Michaud was supported by an ARRA grant from the National
Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
(RC1AR058601). Dr. Neogi was supported by a grant from the NIAMS
(K23AR055127). Dr. Morrison was supported by grants from the NIA
(P30AG028741, K24AG022345, and R01AG030141). Dr. Solomon was supported
by a grant from the NIAMS (K24AR055989). Dr. Von Korff was supported by
grants from the NIDA (R01DA022557) and the NIA (R01AG034181).
NR 106
TC 37
Z9 38
U1 7
U2 19
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1526-2375
J9 PAIN MED
JI Pain Med.
PY 2011
VL 12
IS 9
BP 1336
EP 1357
DI 10.1111/j.1526-4637.2011.01211.x
PG 22
WC Medicine, General & Internal
SC General & Internal Medicine
GA 822MJ
UT WOS:000295051500009
PM 21834914
ER
PT J
AU Marcum, ZA
Perera, S
Donohue, JM
Boudreau, RM
Newman, AB
Ruby, CM
Studenski, SA
Kwoh, CK
Simonsick, EM
Bauer, DC
Satterfield, S
Hanlon, JT
AF Marcum, Zachary A.
Perera, Subashan
Donohue, Julie M.
Boudreau, Robert M.
Newman, Anne B.
Ruby, Christine M.
Studenski, Stephanie A.
Kwoh, C. Kent
Simonsick, Eleanor M.
Bauer, Doug C.
Satterfield, Suzanne
Hanlon, Joseph T.
CA Hlth Aging & Body Composition Stud
TI Analgesic Use for Knee and Hip Osteoarthritis in Community-Dwelling
Elders
SO PAIN MEDICINE
LA English
DT Article
DE Aged; Analgesic; Osteoarthritis
ID CARDIOVASCULAR-DISEASE INDICATORS; OLDER-ADULTS; BODY-COMPOSITION;
HEALTH ABC; PAIN; CARE; RECOMMENDATIONS; MANAGEMENT; PERFORMANCE;
ARTHRITIS
AB Objective. To examine the prevalence and correlates of non-opioid and opioid analgesic use and descriptively evaluate potential undertreatment in a sample of community-dwelling elders with symptomatic knee and/or hip osteoarthritis (OA).
Design. Cross-sectional.
Setting. Health, Aging, and Body Composition Study.
Patients. Six hundred and fifty-two participants attending the year 6 visit (2002-03) with symptomatic knee and/or hip OA.
Outcome Measures. Analgesic use was defined as taking >= 1 non-opioid and/or >= 1 opioid receptor agonist. Non-opioid and opioid doses were standardized across all agents by dividing the daily dose used by the minimum effective analgesic daily dose. Inadequate pain control was defined as severe/extreme OA pain in the past 30 days from a modified Western Ontario and McMaster Universities Osteoarthritis Index.
Results. Just over half (51.4%) reported taking at least one non-opioid analgesic and approximately 10% was taking an opioid, most (88.5%) of whom also took a non-opioid. One in five participants (19.3%) had inadequate pain control, 39% of whom were using <1 standardized daily dose of either a non-opioid or opioid analgesic. In adjusted analyses, severe/extreme OA pain was significantly associated with both non-opioid (adjusted odds ratio [AOR] = 2.44; 95% confidence interval [95% CI] = 1.49-3.99) and opioid (AOR = 2.64; 95% CI = 1.26-5.53) use.
Conclusions. Although older adults with severe/extreme knee and/or hip OA pain are more likely to take analgesics than those with less severe pain, a sizable proportion takes less than therapeutic doses and thus may be undertreated. Further research is needed to examine barriers to optimal analgesic use.
C1 [Marcum, Zachary A.] Univ Pittsburgh, Sch Med, Dept Med Geriatr, Pittsburgh, PA 15213 USA.
[Kwoh, C. Kent] Univ Pittsburgh, Sch Med, Dept Med Rheumatol & Clin Immunol, Pittsburgh, PA 15213 USA.
[Perera, Subashan] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15213 USA.
[Donohue, Julie M.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Policy & Management, Pittsburgh, PA 15213 USA.
[Boudreau, Robert M.; Newman, Anne B.; Hanlon, Joseph T.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA.
[Ruby, Christine M.; Hanlon, Joseph T.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15213 USA.
[Studenski, Stephanie A.; Kwoh, C. Kent; Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res, Pittsburgh, PA USA.
[Studenski, Stephanie A.; Kwoh, C. Kent; Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA.
[Simonsick, Eleanor M.] NIA, Intramural Res Program, Baltimore, MD 21224 USA.
[Bauer, Doug C.] Univ Calif San Francisco, Sch Med, Dept Med Gen Internal Med, San Francisco, CA USA.
[Satterfield, Suzanne] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA.
RP Marcum, ZA (reprint author), Univ Pittsburgh, Sch Med, Dept Med Geriatr, Kaufmann Med Bldg,Suite 500,3471 5th Ave, Pittsburgh, PA 15213 USA.
EM zam12@pitt.edu
RI Perera, Subashan/D-7603-2014; Newman, Anne/C-6408-2013;
OI Newman, Anne/0000-0002-0106-1150; Boudreau, Robert/0000-0003-0162-5187;
Donohue, Julie/0000-0003-2418-6017
FU National Institute on Aging [R01AG027017, P30AG024827, T32 AG021885,
K07AG033174, R01AG034056, N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106];
National Institute of Mental Health [R34 MH082682]; National Institute
of Nursing Research [R01 NR010135]; Agency for Healthcare Research and
Quality [R01 HS017695]; VA Health Services [IIR-06-062]; NIH, National
Institute on Aging
FX This study was primarily supported by National Institute on Aging grants
and contracts (R01AG027017, P30AG024827, T32 AG021885, K07AG033174,
R01AG034056, N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106), a
National Institute of Mental Health grant (R34 MH082682), a National
Institute of Nursing Research grant (R01 NR010135), an Agency for
Healthcare Research and Quality grant (R01 HS017695), and a VA Health
Services Research grant (IIR-06-062). This research was also supported
in part by the Intramural Research program of the NIH, National
Institute on Aging. The authors would like to thank Yihuang Kang and Yan
Zheng for their assistance with data programming.
NR 35
TC 12
Z9 12
U1 1
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1526-2375
J9 PAIN MED
JI Pain Med.
PY 2011
VL 12
IS 11
BP 1628
EP 1636
DI 10.1111/j.1526-4637.2011.01249.x
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 854PO
UT WOS:000297506900009
PM 21992521
ER
PT J
AU Lansford, JE
Bornstein, MH
AF Lansford, Jennifer E.
Bornstein, Marc H.
TI Parenting Attributions and Attitudes in Diverse Cultural Contexts:
Introduction to the Special Issue
SO PARENTING-SCIENCE AND PRACTICE
LA English
DT Article
ID CHILD-REARING ORIENTATIONS; FAMILY; MOTHERS; SELF; BEHAVIOR; BELIEFS;
INDIVIDUALISM; COLLECTIVISM; INSTRUMENTS; PERSONALITY
AB This Introduction describes the conceptual rationale, the general methods of the Parenting Across Cultures Project, and the analytic plan adopted in the articles in this special issue. Each article that follows this Introduction describes the parenting context and mothers' and fathers' attributions for successes and failures in caregiving and progressive versus authoritarian childrearing attitudes in each of nine countries: China, Colombia, Italy, Jordan, Kenya, the Philippines, Sweden, Thailand, and the United States. Results in each article address questions of similarities and differences in mothers' and fathers' attributions and attitudes and how highly mothers' attributions and attitudes are correlated with fathers' attributions and attitudes within a national group. The special issue concludes with an article that draws connections among the findings across the nine countries and outlines implications of similarities and differences between mothers' and fathers' parenting attributions and attitudes.
C1 [Lansford, Jennifer E.] Duke Univ, Ctr Child & Family Policy, Durham, NC 27708 USA.
[Bornstein, Marc H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD USA.
RP Lansford, JE (reprint author), Duke Univ, Ctr Child & Family Policy, Box 90545, Durham, NC 27708 USA.
EM lansford@duke.edu
NR 85
TC 14
Z9 14
U1 2
U2 19
PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS
PI PHILADELPHIA
PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA
SN 1529-5192
J9 PARENT-SCI PRACT
JI Parent.-Sci. Pract.
PY 2011
VL 11
IS 2-3
SI SI
BP 87
EP 101
DI 10.1080/15295192.2011.585552
PG 15
WC Family Studies; Psychology, Developmental
SC Family Studies; Psychology
GA 885KE
UT WOS:000299777100001
ER
PT J
AU Lansford, JE
Bornstein, MH
Dodge, KA
Skinner, AT
Putnick, DL
Deater-Deckard, K
AF Lansford, Jennifer E.
Bornstein, Marc H.
Dodge, Kenneth A.
Skinner, Ann T.
Putnick, Diane L.
Deater-Deckard, Kirby
TI Attributions and Attitudes of Mothers and Fathers in the United States
SO PARENTING-SCIENCE AND PRACTICE
LA English
DT Article
ID AFRICAN-AMERICAN; IMMIGRANT FAMILIES; BEHAVIOR PROBLEMS; ACHIEVEMENT;
CHILDREN; METAANALYSIS; PERCEPTIONS; ENVIRONMENT; PATTERNS; PARENTS
AB Objective. The present study examined mean level similarities and differences as well as correlations between U. S. mothers' and fathers' attributions regarding successes and failures in caregiving situations and progressive versus authoritarian attitudes. Design. Interviews were conducted with mothers and fathers in 139 European American, Latin American, and African American families. Results. Interactions between parent gender and ethnicity emerged for adult-controlled failure and perceived control over failure. Fathers reported higher adult-controlled failure and child-controlled failure attributions than did mothers, whereas mothers reported attitudes that were more progressive and modern than did fathers; these differences remained significant after controlling for parents' age, education, and possible social desirability bias. Ethnic differences emerged for 5 of the 7 attributions and attitudes examined; 4 remained significant after controlling for parents' age, education, and possible social desirability bias. Medium effect sizes were found for concordance between parents in the same family for attributions regarding uncontrollable success, child-controlled failure, progressive attitudes, authoritarian attitudes, and modernity of attitudes after controlling for parents' age, education, and possible social desirability bias. Conclusions. This work elucidates ways that parent gender and ethnicity relate to attributions regarding U. S. parents' successes and failures in caregiving situations and to their progressive versus authoritarian parenting attitudes.
C1 [Lansford, Jennifer E.] Duke Univ, Ctr Child & Family Policy, Durham, NC 27708 USA.
[Bornstein, Marc H.; Putnick, Diane L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD USA.
[Deater-Deckard, Kirby] Virginia Tech, Blacksburg, VA 24060 USA.
RP Lansford, JE (reprint author), Duke Univ, Ctr Child & Family Policy, Box 90545, Durham, NC 27708 USA.
EM lansford@duke.edu
OI Putnick, Diane/0000-0002-6323-749X
FU FIC NIH HHS [R03 TW008141-01, R03 TW008141]; NICHD NIH HHS [R01
HD054805, R01 HD054805-01A1]; NIDA NIH HHS [K05 DA015226-01, K05
DA015226]
NR 57
TC 18
Z9 18
U1 0
U2 10
PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS
PI PHILADELPHIA
PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA
SN 1529-5192
J9 PARENT-SCI PRACT
JI Parent.-Sci. Pract.
PY 2011
VL 11
IS 2-3
SI SI
BP 199
EP 213
DI 10.1080/15295192.2011.585567
PG 15
WC Family Studies; Psychology, Developmental
SC Family Studies; Psychology
GA 885KE
UT WOS:000299777100010
PM 21822402
ER
PT J
AU Bornstein, MH
Putnick, DL
Lansford, JE
AF Bornstein, Marc H.
Putnick, Diane L.
Lansford, Jennifer E.
TI Parenting Attributions and Attitudes in Cross-Cultural Perspective
SO PARENTING-SCIENCE AND PRACTICE
LA English
DT Article
ID CHILD-REARING ORIENTATIONS; YOUNG-CHILDREN; BEHAVIOR; SELF; ACHIEVEMENT;
AGREEMENT; MOTHERS; FAMILY; STYLE; METAANALYSIS
AB Objective. This article used the Parenting Across Cultures Project to evaluate similarities and differences in mean levels and relative agreement between mothers' and fathers' attributions and attitudes in parenting in 9 countries. Design. Mothers and fathers reported their perceptions of causes of successes and failures in caregiving and their progressive versus authoritarian childrearing attitudes. Gender and cultural similarities and differences in parents' attributions and attitudes in 9 countries were analyzed: China, Colombia, Italy, Jordan, Kenya, the Philippines, Sweden, Thailand, and the United States. Results. Although mothers and fathers did not differ in any attribution, mothers reported more progressive parenting attitudes and modernity of childrearing attitudes than did fathers, and fathers reported more authoritarian attitudes than did mothers. Country differences also emerged in all attributions and attitudes that were examined. Mothers' and fathers' attributions and their attitudes were moderately correlated, but parenting attitudes were more highly correlated in parents than were attributions. Conclusions. We draw connections among the findings across the 9 countries and outline implications for understanding similarities and differences in mothers' and fathers' parenting attributions and attitudes.
C1 [Bornstein, Marc H.; Putnick, Diane L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
[Lansford, Jennifer E.] Duke Univ, Durham, NC 27706 USA.
RP Bornstein, MH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA.
EM marc_h_bornstein@nih.gov
OI Putnick, Diane/0000-0002-6323-749X
FU FIC NIH HHS [R03 TW008141, R03 TW008141-01]; NICHD NIH HHS [R01
HD054805, R01 HD054805-01A1]
NR 85
TC 14
Z9 14
U1 4
U2 27
PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS
PI PHILADELPHIA
PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA
SN 1529-5192
J9 PARENT-SCI PRACT
JI Parent.-Sci. Pract.
PY 2011
VL 11
IS 2-3
SI SI
BP 214
EP 237
DI 10.1080/15295192.2011.585568
PG 24
WC Family Studies; Psychology, Developmental
SC Family Studies; Psychology
GA 885KE
UT WOS:000299777100011
PM 21927591
ER
PT J
AU Flood, PM
Qian, L
Peterson, LJ
Zhang, F
Shi, JS
Gao, HM
Hong, JS
AF Flood, Patrick M.
Qian, Li
Peterson, Lynda J.
Zhang, Feng
Shi, Jing-Shan
Gao, Hui-Ming
Hong, Jau-Shyong
TI Transcriptional Factor NF-kappa B as a Target for Therapy in Parkinson's
Disease
SO PARKINSONS DISEASE
LA English
DT Review
AB Parkinson's disease (PD) is a neurodegenerative condition characterized by chronic inflammation. Nuclear factor kappa B (NF-kappa B) is a family of inducible transcription factors that are expressed in a wide variety of cells and tissues, including microglia, astrocytes, and neurons, and the classical NF-kappa B pathway plays a key role in the activation and regulation of inflammatory mediator production during inflammation. Activation of the classical NF-kappa B pathway is mediated through the activity of the IKK kinase complex, which consists of a heterotrimer of IKK alpha, IKK beta, and IKK gamma subunits. Targeting NF-kappa B has been proposed as an approach to the treatment of acute and chronic inflammatory conditions, and the use of inhibitors specific for either IKK beta or IKK gamma has now been found to inhibit neurodegeneration of TH+ DA-producing neurons in murine and primate models of Parkinson's disease. These studies suggest that targeting the classical pathway of NF-kappa B through the inhibition of the IKK complex can serve as a useful therapeutic approach to the treatment of PD.
C1 [Flood, Patrick M.; Qian, Li; Peterson, Lynda J.] Univ N Carolina, Dept Periodontol & Comprehens Ctr Inflammatory Di, Chapel Hill, NC 27599 USA.
[Zhang, Feng; Shi, Jing-Shan] Zunji Med Coll, Dept Pharmacol, Zunji, Peoples R China.
[Zhang, Feng; Shi, Jing-Shan] Zunji Med Coll, Key Lab Pharmacol Guizhou, Zunji, Peoples R China.
[Zhang, Feng; Gao, Hui-Ming; Hong, Jau-Shyong] NIEHS, Neuropharmacol Sect, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
RP Flood, PM (reprint author), Univ N Carolina, Dept Periodontol & Comprehens Ctr Inflammatory Di, Chapel Hill, NC 27599 USA.
EM pat_flood@dentistry.unc.edu
NR 104
TC 6
Z9 6
U1 0
U2 2
PU HINDAWI PUBLISHING CORPORATION
PI NEW YORK
PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA
SN 2090-8083
J9 PARKINSONS DIS-US
JI Parkinsons Dis.
PY 2011
AR UNSP 216298
DI 10.4061/2011/216298
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA V29RN
UT WOS:000208765600014
ER
PT J
AU Imai, Y
Venderova, K
Park, DS
Cai, HB
Schmidt, E
AF Imai, Yuzuru
Venderova, Katerina
Park, David S.
Cai, Huaibin
Schmidt, Enrico
TI Animal Models of Parkinson's Disease
SO PARKINSONS DISEASE
LA English
DT Editorial Material
C1 [Imai, Yuzuru] Juntendo Univ, Grad Sch Med, Dept Neurosci Neurodegenerat Disorders, Tokyo 1138421, Japan.
[Venderova, Katerina] Univ Pacific, Dept Physiol & Pharmacol, Thomas J Long Sch Pharm & Hlth Sci, Stockton, CA 95211 USA.
[Park, David S.] Ottawa Hlth Res Inst, Neurosci Res Inst, Ottawa, ON K1H 8M5, Canada.
[Cai, Huaibin] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Schmidt, Enrico] Univ Freiburg, Dept Bioinformat & Mol Genet, D-79104 Freiburg, Germany.
[Schmidt, Enrico] Univ Freiburg, Ctr Biol Syst Anal, D-79104 Freiburg, Germany.
RP Imai, Y (reprint author), Juntendo Univ, Grad Sch Med, Dept Neurosci Neurodegenerat Disorders, Tokyo 1138421, Japan.
EM yzimai@juntendo.ac.jp
NR 0
TC 1
Z9 1
U1 0
U2 0
PU HINDAWI PUBLISHING CORPORATION
PI NEW YORK
PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA
SN 2090-8083
J9 PARKINSONS DIS-US
JI Parkinsons Dis.
PY 2011
AR UNSP 364328
DI 10.4061/2011/364328
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA V29RN
UT WOS:000208765600029
ER
PT J
AU Leong, ASY
Zhuang, ZP
AF Leong, Anthony S. -Y.
Zhuang, Zhengping
TI The Changing Role of Pathology in Breast Cancer Diagnosis and Treatment
SO PATHOBIOLOGY
LA English
DT Article
DE Breast cancer; Immunohistochemistry; Molecular technology; Biomarkers;
Prognosis; Predictive markers; Proteomics; Drug discovery; Stem cells
ID COMPARATIVE GENOMIC HYBRIDIZATION; CARCINOMA IN-SITU; ESTROGEN-RECEPTOR
STATUS; COPY-NUMBER CHANGES; GENE-EXPRESSION DATA; QUANTITATIVE RT-PCR;
BASAL-LIKE SUBTYPE; DUCTAL CARCINOMA; STEM-CELLS; PROTEIN EXPRESSION
AB Pathological examination has been the gold standard for diagnosis in cancer and its role has also included the elucidation of etiology, pathogenesis, clinicopathological correlation, and prognostication. The advent of newer technologies and the realization that breast cancer is heterogeneous has shifted the focus to prognostication, with increased attention being paid to the identification of morphological features and immunohistochemical markers of prognostic relevance. However, despite the massive efforts invested in the identification of immunohistochemical biomarkers in breast cancer the majority have not proven to be of value in multivariate analyses and only estrogen receptor, progesterone receptor, and Her2/neu expression have remained essential components of pathological examination. These 3 markers were initially employed for prognostication but their role in treatment also rendered them of predictive value. Newer molecular methods, especially high-throughput technologies, have shown that even morphologically similar subtypes of breast cancer can show molecular heterogeneity; moreover, infiltrating ductal carcinoma can be separated into at least 4 molecular subtypes designated luminal (ER+, PR+, and Her2/neu-), Her2 overexpressing (ER-, PR-, and Her2/neu+), basal-like (ER-, PR-, Her2/neu-, and CK5/6+, EGFR+), and normal breast-like (ER-, PR-, and Her2/neu-), each with different clinical outcomes. The importance of proliferative gene expression in these subtypes has been demonstrated and surrogate immunohistochemical markers include ER, PR, Her2/neu, and Ki67 for the more expensive molecular tests. Molecular technologies, importantly, have not only provided further insights into the heterogeneity of breast cancer but have also opened new avenues for treatment through the identification of signaling molecules important in the proliferation and survival of the neoplastic cells. The treatment of cancer thus shifts from the conventional approach of 'one size fits all' to one of personalized treatment tailored to the specific characteristics of the tumor. Pathologists continue to play their traditional role in diagnosis but, as purveyors of the excised tissue, pathologists now have the additional role of identifying biomarkers responsive to therapeutic manipulation, thus playing an inextricable role as diagnostic oncologists in the management of breast cancer. Copyright (C) 2011 S. Karger AG, Basel
C1 [Leong, Anthony S. -Y.] Univ Newcastle, Hunter Area Pathol Serv, HRMC, Newcastle, NSW 2310, Australia.
[Zhuang, Zhengping] NIH, Mol Pathogenesis Unit, Bethesda, MD 20892 USA.
RP Leong, ASY (reprint author), Univ Newcastle, Hunter Area Pathol Serv, HRMC, Locked Bag 1, Newcastle, NSW 2310, Australia.
EM aleong@mail.newcastle.edu.au
NR 169
TC 32
Z9 36
U1 1
U2 9
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 1015-2008
J9 PATHOBIOLOGY
JI Pathobiology
PY 2011
VL 78
IS 2
BP 99
EP 114
DI 10.1159/000292644
PG 16
WC Cell Biology; Pathology
SC Cell Biology; Pathology
GA 778TR
UT WOS:000291729700005
PM 21677473
ER
PT S
AU Kino, T
Chrousos, GP
AF Kino, Tomoshige
Chrousos, George P.
BE Ghizzoni, L
Cappa, M
Chrousos, G
Loche, S
Maghnie, M
TI Circadian CLOCK-Mediated Regulation of Target-Tissue Sensitivity to
Glucocorticoids: Implications for Cardiometabolic Diseases
SO PEDIATRIC ADRENAL DISEASES
SE Endocrine Development
LA English
DT Proceedings Paper
CT Pediatric Adrenal Diseases Workshop
CT 2nd International Shallow-Water Acoustics Conference
CY MAY 16-18, 2010
CY SEP 16-20, 2009
CL Turin, ITALY
CL Shanghai, PEOPLES R CHINA
SP Off Naval Res, Chinese Acad Sci, Acoust Soc China, Acoust Soc Amer, Natl Nat Sci Fdn China
ID PITUITARY-ADRENAL AXIS; METABOLIC SYNDROME; SOMATIC DISORDERS;
DNA-BINDING; RECEPTOR; TRANSCRIPTION; COMPLEX; STRESS; EXPRESSION;
CROSSTALK
AB Glucocorticoids, the end-products of the hypothalamic-pituitary-adrenal (HPA) axis, influence the functions of virtually all organs and tissues through the nuclear glucocorticoid receptor (GR). Circulating levels of glucocorticoids fluctuate naturally in a circadian fashion under the strong influence of the hypothalamic suprachiasmatic nucleus (SCN) circadian CLOCK system, and regulate the transcriptional activity of the GR in the brain and peripheral target tissues. We recently reported that the basic helix-loop-helix transcription factor Clock, which is a histone acetyltransferase and a central component of the self-oscillating transcription factor loop that generates circadian rhythms, represses GR transcriptional activity by acetylating lysine residues within the lysine cluster' located in the hinge region of the receptor. This Clock-mediated repression of GR transcriptional activity oscillates in inverse phase to the HPA axis, acting as a target tissue counter-regulatory mechanism to the diurnally fluctuating circulating glucocorticoids. Interestingly, mild evening elevations of cortisol, as occurs in chronic stress situations, and frequent uncoupling of the SCN CLOCK-directed HPA axis from the daily oscillation of target tissue sensitivity to glucocorticoids, as happens in trans-time zone travel and night shift work, produce functional hypercortisolism and, hence, multiple components of the metabolic syndrome with resultant cardiovascular complications. Copyright (C) 2011 S. Karger AG, Basel
C1 [Kino, Tomoshige] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Mol Hormone Act, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
RP Chrousos, GP (reprint author), Univ Athens, Sch Med, Aghia Sohia Childrens Hosp, Dept Pediat 1, GR-11527 Athens, Greece.
EM chrousge@med.uoa.gr
FU Intramural NIH HHS [ZIA HD008732-09]
NR 46
TC 24
Z9 24
U1 0
U2 5
PU KARGER
PI BASEL
PA POSTFACH, CH-4009 BASEL, SWITZERLAND
SN 1421-7082
BN 978-3-8055-9643-5
J9 ENDOCR DEV
JI Endocr. Dev.
PY 2011
VL 20
BP 116
EP 126
PG 11
WC Endocrinology & Metabolism; Pediatrics
SC Endocrinology & Metabolism; Pediatrics
GA BTJ75
UT WOS:000287122700012
PM 21164265
ER
PT S
AU Lui, JC
Baron, J
AF Lui, Julian C.
Baron, Jeffrey
BE Ghizzoni, L
Cappa, M
Chrousos, G
Loche, S
Maghnie, M
TI Effects of Glucocorticoids on the Growth Plate
SO PEDIATRIC ADRENAL DISEASES
SE Endocrine Development
LA English
DT Proceedings Paper
CT Pediatric Adrenal Diseases Workshop
CT 2nd International Shallow-Water Acoustics Conference
CY MAY 16-18, 2010
CY SEP 16-20, 2009
CL Turin, ITALY
CL Shanghai, PEOPLES R CHINA
SP Off Naval Res, Chinese Acad Sci, Acoust Soc China, Acoust Soc Amer, Natl Nat Sci Fdn China
ID CATCH-UP GROWTH; LONGITUDINAL BONE-GROWTH; EPIPHYSEAL FUSION; RESTING
ZONE; DEXAMETHASONE; CHONDROCYTES; SENESCENCE; RETARDATION; EXPRESSION;
RECEPTOR
AB Glucocorticoids have a direct, inhibitory effect on the growth plate, as demonstrated by in vivo and organ culture studies. Glucocorticoids slow longitudinal bone growth by inhibiting chondrocyte proliferation, hypertrophy, and cartilage matrix synthesis. The molecular mediators of these effects are poorly understood. Glucocorticoids also delay growth plate senescence. The decreased rate of senescence appears to be a consequence of the growth inhibition and, in particular, may occur because glucocorticoids slow proliferation of stem-like cells in the resting zone and therefore conserve the limited proliferative capacity of these cells. This slowing of senescence appears to explain the phenomenon of catch-up growth following transient glucocorticoid exposure. After the exposure, the growth plate is less senescent, and therefore grows more rapidly than is normal for age. Glucocorticoids cause growth inhibition and subsequent catch-up growth not only in terms of longitudinal bone growth at the growth plate but also in terms of cross-sectional bone growth at the periosteum. Whether the underlying mechanisms are analogous to those at the growth plate is not known. Copyright (C) 2011 S. Karger AG, Basel
C1 [Baron, Jeffrey] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Dev Endocrinol Branch, Program Dev Endocrinol & Genet, NIH,CRC, Bethesda, MD 20892 USA.
RP Baron, J (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Dev Endocrinol Branch, Program Dev Endocrinol & Genet, NIH,CRC, Room 1-3330,10 Ctr Dr,MSC-1103, Bethesda, MD 20892 USA.
EM jeffrey.baron@nih.gov
RI Lui, Chun Kin Julian/E-2253-2012
FU Intramural NIH HHS [ZIA HD000640-16]
NR 26
TC 11
Z9 11
U1 0
U2 4
PU KARGER
PI BASEL
PA POSTFACH, CH-4009 BASEL, SWITZERLAND
SN 1421-7082
BN 978-3-8055-9643-5
J9 ENDOCR DEV
JI Endocr. Dev.
PY 2011
VL 20
BP 187
EP 193
PG 7
WC Endocrinology & Metabolism; Pediatrics
SC Endocrinology & Metabolism; Pediatrics
GA BTJ75
UT WOS:000287122700019
PM 21164272
ER
PT J
AU Meier, ER
Byrnes, C
Weissman, M
Noel, P
Luban, NLC
Miller, JL
AF Meier, Emily Riehm
Byrnes, Colleen
Weissman, Maxine
Noel, Pierre
Luban, Naomi L. C.
Miller, Jeffery L.
TI Expression Patterns of Fetal Hemoglobin in Sickle Cell Erythrocytes Are
Both Patient- and Treatment-Specific During Childhood
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE F cells; fetal hemoglobin; sickle cell disease
ID DISEASE; CHILDREN; HYDROXYUREA; MANAGEMENT; ANEMIA
AB Background Treatment associated fetal hemoglobin (HbF) expression patterns in children with sickle cell disease (SCD) have not been fully described The objective of this study was to corn pare HbF expression profiles (HbF and F cells) in the peripheral blood of pediatric SCD patients receiving hydroxyurea (HU) chronic transfusions (Tx) or no chronic therapy (Ctrl) Procedure Peripheral blood samples were collected from SCD patients between 1 month and 21 years of age and immunostained with anti HbF and anti HbA antibodies Erythrocytes containing HbF (F cells) were enumerated with this dual staining method HbF was measured using chromatography (HPLC) Results Blood from 44 Ctrl patients <= 4 years of age was compared with that from older children (50 Ctrl 17 HU 17 Tx) Among the older children, the percentage of both HbF and F ails in the Tx group was significantly decreased compared to the control (HbF 5 4 +/- 4 2% vs 11 0 +/- 7 2%, P=0 003 F cells 302 +/- 16 3% vs 43 8 +/- 20 4%, P = 0 0071) While the distribution of F cells was significantly increased in the HU group (56 3 +/- 17 1% vs 43 8 20 4%, P=0 016), the increase in HbF was less robust (14 7 +/- 6 4% vs 11 0 +/- 7 2% P = 0 051) Positive correlations of HbF and F cell distributions were noted in all groups (P <0 0001 for all groups) In serial samples from individual patients relatively static patterns of HbF and F cell distribution were noted Conclusion Pediatric SCD patients possess distinct patterns of HbF switching and silencing in peripheral blood erythrocytes Thereafter, erythrocyte HbF expression level and distribution are maintained with both patient and treatment specific patterns that may be useful for predicing the need or response to HbF modulating therapy Pediatr Blood Cancer 2011,56 103-109 (C) 2010 Wiley Liss Inc
C1 [Meier, Emily Riehm; Byrnes, Colleen; Miller, Jeffery L.] NIDDK, Mol Med Branch, NIH, Bethesda, MD 20892 USA.
[Meier, Emily Riehm; Luban, Naomi L. C.] Childrens Natl Med Ctr, Ctr Canc & Blood Disorders, Washington, DC 20010 USA.
[Weissman, Maxine; Noel, Pierre] NIH, Dept Lab Med, Hematol Serv, Bethesda, MD 20892 USA.
[Luban, Naomi L. C.] George Washington Univ, Dept Pediat, Med Ctr, Washington, DC 20052 USA.
RP Miller, JL (reprint author), NIDDK, Mol Med Branch, NIH, 10 Ctr Dr,Bldg 10,Room 9N311, Bethesda, MD 20892 USA.
FU NIH; NIDDK NIH; Children's National Medical Center
FX Grant sponsor NIH; This research was supported by the Intramural
Research Program of the NIDDK NIH Dr Meier is a scholar in the DC
Clinical Research Training Consortium a K30 funded clinical research
training program and the recipient of the Tucker Foundation Fellowship
at Children's National Medical Center
NR 23
TC 7
Z9 7
U1 0
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD JAN
PY 2011
VL 56
IS 1
BP 103
EP 109
DI 10.1002/pbc.22643
PG 7
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 687PM
UT WOS:000284790400020
PM 21108444
ER
PT J
AU Hull, JJ
Teel, EN
Kerin, TK
Freeman, MM
Esona, MD
Gentsch, JR
Cortese, MM
Parashar, UD
Glass, RI
Bowen, MD
AF Hull, Jennifer J.
Teel, Elizabeth N.
Kerin, Tara K.
Freeman, Molly M.
Esona, Mathew D.
Gentsch, Jon R.
Cortese, Margaret M.
Parashar, Umesh D.
Glass, Roger I.
Bowen, Michael D.
CA National Rotavirus Strain Surveill
TI United States Rotavirus Strain Surveillance From 2005 to 2008 Genotype
Prevalence Before and After Vaccine Introduction
SO PEDIATRIC INFECTIOUS DISEASE JOURNAL
LA English
DT Article
DE RotaTeq; rotavirus; strain; surveillance; US
ID POLYMERASE CHAIN-REACTION; VP4 GENE; POPULATION; GASTROENTERITIS;
IDENTIFICATION; DIVERSITY; CHILDREN; PREVENTION; REDUCTION; ROTARIX
AB Background: A live, attenuated rotavirus vaccine, RotaTeq (R), was approved in 2006 for immunization of infants in the United States. To monitor the distribution of rotavirus genotypes before and after vaccine introduction, the Centers for Disease Control and Prevention conducted strain surveillance with the National Rotavirus Strain Surveillance System.
Methods: Over 3 rotavirus seasons, 2005-2006, 2006-2007, and 2007-2008, National Rotavirus Strain Surveillance System laboratories collected rotavirus-positive stool specimens and submitted them to the Centers for Disease Control and Prevention. Rotavirus strains were G- and P-genotyped by multiplex reverse transcription-polymerase chain reaction or nucleotide sequencing.
Results: During 2005-2006 and 2006-2007 seasons, G I was the dominant G-type but in the 2007-2008 season, G3 replaced GI as the most frequently detected strain. Four genotypes, G1P[8], G2P[4], G3P[8], and G9P[8] were detected in every season. Uncommon strains observed during the study period were G2P[8], G1P[6], G2P[6], G4P[6], G1P[4], G3P[9], G12P [6], and G12P[8]. The mean age of rotavirus cases in the 2007-2008 season increased significantly in patients less than 3 years old compared with the 2 previous seasons.
Conclusions: The increased overall prevalence of G3P [8] strains in 2007-2008, the first rotavirus season with reasonable rotavirus vaccine coverage, was consistent with Australian reports of G3 dominance following RotaTeq introduction. However, these strain changes in both countries have occurred in the context of large declines in severe rotavirus disease and we cannot rule out that they are simply the result of naturally occurring changes in rotavirus strain prevalence. These findings underscore the need for careful monitoring of strains to assess possible vaccine pressure-induced changes and vaccine effectiveness against various rotavirus genotypes.
C1 [Hull, Jennifer J.; Teel, Elizabeth N.; Kerin, Tara K.; Freeman, Molly M.; Esona, Mathew D.; Gentsch, Jon R.; Glass, Roger I.; Bowen, Michael D.] Ctr Dis Control & Prevent, Gastroenteritis & Resp Viruses Lab Branch, Div Viral Dis, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA.
[Cortese, Margaret M.; Parashar, Umesh D.] Ctr Dis Control & Prevent, Epidemiol Branch, Div Viral Dis, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA.
[Glass, Roger I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Bowen, MD (reprint author), Ctr Dis Control & Prevent, Gastroenteritis & Resp Viruses Lab Branch, Div Viral Dis, Natl Ctr Immunizat & Resp Dis, Roybal Campus,Mailstop G04,1600 Clifton Rd NE, Atlanta, GA 30333 USA.
EM MKB6@CDC.GOV
NR 33
TC 89
Z9 90
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0891-3668
J9 PEDIATR INFECT DIS J
JI Pediatr. Infect. Dis. J.
PD JAN
PY 2011
VL 30
IS 1
SU S
BP S42
EP S47
DI 10.1097/INF.0b013e3181fefd78
PG 6
WC Immunology; Infectious Diseases; Pediatrics
SC Immunology; Infectious Diseases; Pediatrics
GA 701EA
UT WOS:000285795900009
PM 21183839
ER
PT J
AU Hintz, SR
Kendrick, DE
Wilson-Costello, DE
Das, A
Bell, EF
Vohr, BR
Higgins, RD
AF Hintz, Susan R.
Kendrick, Douglas E.
Wilson-Costello, Deanne E.
Das, Abhik
Bell, Edward F.
Vohr, Betty R.
Higgins, Rosemary D.
CA NICHD Neonatal Res Network
TI Early-Childhood Neurodevelopmental Outcomes Are Not Improving for
Infants Born at < 25 Weeks' Gestational Age
SO PEDIATRICS
LA English
DT Article
DE extremely preterm; neurodevelopmental; outcome; cerebral palsy; Bayley
Scales of Infant Development II
ID BIRTH-WEIGHT INFANTS; EXTREMELY PRETERM BIRTH; PERINATAL MANAGEMENT;
COGNITIVE FUNCTION; CHILDREN; MOTOR; LESS; CARE
AB OBJECTIVE: We compared neurodevelopmental outcomes at 18 to 22 months' corrected age of infants born with extremely low birth weight at an estimated gestational age of <25 weeks during 2 periods: 1999-2001 (epoch 1) and 2002-2004 (epoch 2).
PATIENTS AND METHODS: We conducted a multicenter, retrospective analysis of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Perinatal and neonatal variables and outcomes were compared between epochs. Neurodevelopmental outcomes at 18 to 22 months' corrected age were evaluated with neurologic exams and Bayley Scales of Infant Development II. Logistic regression analyses determined the independent risk of epoch for adverse outcomes.
RESULTS: Infant survival was similar between epochs (epoch 1, 35.4%, vs epoch 2, 32.3%; P = .09). A total of 411 of 452 surviving infants in epoch 1 and 405 of 438 surviving infants in epoch 2 were evaluated at 18 to 22 months' corrected age. Cesarean delivery (P = .03), surgery for patent ductus arteriosus (P = .004), and late sepsis (P = .01) were more common in epoch 2, but postnatal steroid use was dramatically reduced (63.5% vs 32.8%; P < .0001). Adverse outcomes at 18 to 22 months' corrected age were common in both epochs. Moderate-to-severe cerebral palsy was diagnosed in 11.1% of surviving infants in epoch 1 and 14.9% in epoch 2 (adjusted odds ratio [OR]: 1.52 [95% confidence interval (CI): 0.86-2.71]; P = .15), the Mental Developmental Index was <70 in 44.9% in epoch 1 and 51% in epoch 2 (OR: 1.30 [95% CI: 0.91-1.87]; P = .15), and neurodevelopmental impairment was diagnosed in 50.1% of surviving infants in epoch 1 and 58.7% in epoch 2 (OR: 1.4 [95% CI: 0.98-2.04]; P = .07).
CONCLUSIONS: Early-childhood outcomes for infants born at <25 weeks' estimated gestational age were unchanged between the 2 periods. Pediatrics 2011;127:62-70
C1 [Hintz, Susan R.] Stanford Univ, Sch Med, Div Neonatol, Dept Pediat, Palo Alto, CA 94304 USA.
[Kendrick, Douglas E.] RTI Int, Stat & Epidemiol Unit, Res Triangle Pk, NC USA.
[Wilson-Costello, Deanne E.] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA.
[Das, Abhik] RTI Int, Stat & Epidemiol Unit, Rockville, MD USA.
[Bell, Edward F.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA.
[Vohr, Betty R.] Brown Univ, Women & Infants Hosp, Dept Pediat, Providence, RI 02908 USA.
[Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Hintz, SR (reprint author), Stanford Univ, Sch Med, Div Neonatal & Dev Med, Dept Pediat, 750 Welch Rd,Suite 315, Palo Alto, CA 94304 USA.
EM srhintz@stanford.edu
FU National Institutes of Health; NICHD
FX The National Institutes of Health and the NICHD provided grant support
for the NRN's generic database and follow-up studies. Data collected at
participating sites of the NICHD NRN were transmitted to RTI
International, the data coordinating center (DCC) for the network, which
stored, managed, and analyzed the data for this study. On behalf of the
NRN, Dr Abhik Das (DCC Principal Investigator) and Mr Douglas Kendrick
(DCC Statistician) had full access to all the data in the study and take
responsibility for the integrity of the data and accuracy of the data
analysis.
NR 29
TC 69
Z9 70
U1 2
U2 2
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
J9 PEDIATRICS
JI Pediatrics
PD JAN
PY 2011
VL 127
IS 1
BP 62
EP 70
DI 10.1542/peds.2010-1150
PG 9
WC Pediatrics
SC Pediatrics
GA 700YT
UT WOS:000285782200046
PM 21187312
ER
PT J
AU Ambalavanan, N
Walsh, M
Bobashev, G
Das, A
Levine, B
Carlo, WA
Higgins, RD
AF Ambalavanan, Namasivayam
Walsh, Michele
Bobashev, Georgiy
Das, Abhik
Levine, Burton
Carlo, Waldemar A.
Higgins, Rosemary D.
TI Intercenter Differences in Bronchopulmonary Dysplasia or Death Among
Very Low Birth Weight Infants
SO PEDIATRICS
LA English
DT Article
DE logistic models; infant; premature; predictive value of tests;
clustering
ID NEONATAL INTENSIVE-CARE; QUALITY IMPROVEMENT; PRETERM INFANTS; OUTCOMES;
RATES
AB OBJECTIVES: To determine (1) the magnitude of clustering of bronchopulmonary dysplasia (36 weeks) or death (the outcome) across centers of the Eunice Kennedy Shriver National Institute of Child and Human Development National Research Network, (2) the infant-level variables associated with the outcome and estimate their clustering, and (3) the center-specific practices associated with the differences and build predictive models.
METHODS: Data on neonates with a birth weight of <1250 g from the cluster-randomized benchmarking trial were used to determine the magnitude of clustering of the outcome according to alternating logistic regression by using pairwise odds ratio and predictive modeling. Clinical variables associated with the outcome were identified by using multivariate analysis. The magnitude of clustering was then evaluated after correction for infant-level variables. Predictive models were developed by using center-specific and infant-level variables for data from 2001 2004 and projected to 2006.
RESULTS: In 2001-2004, clustering of bronchopulmonary dysplasia/death was significant (pairwise odds ratio: 1.3; P < .001) and increased in 2006 (pairwise odds ratio: 1.6; overall incidence: 52%; range across centers: 32%-74%); center rates were relatively stable over time. Variables that varied according to center and were associated with increased risk of outcome included lower body temperature at NICU admission, use of prophylactic indomethacin, specific drug therapy on day 1, and lack of endotracheal intubation. Center differences remained significant even after correction for clustered variables.
CONCLUSION: Bronchopulmonary dysplasia/death rates demonstrated moderate clustering according to center. Clinical variables associated with the outcome were also clustered. Center differences after correction of clustered variables indicate presence of as-yet unmeasured center variables. Pediatrics 2011;127:e106-e116
C1 [Ambalavanan, Namasivayam; Carlo, Waldemar A.] Univ Alabama, Dept Pediat, Birmingham, AL 35249 USA.
[Walsh, Michele] Case Western Reserve Univ, Dept Pediat, Cleveland, OH 44106 USA.
[Bobashev, Georgiy; Das, Abhik; Levine, Burton] RTI Int, Res Triangle Pk, NC USA.
[Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Higgins, Rosemary D.] Dev Neonatal Res Network, Bethesda, MD USA.
RP Ambalavanan, N (reprint author), Univ Alabama, Dept Pediat, 176F Suite 9380,619 S 20th St, Birmingham, AL 35249 USA.
EM ambal@uab.edu
OI Ambalavanan, Namasivayam/0000-0003-0731-9092
FU National Institutes of Health; Eunice Kennedy Shriver National Institute
of Child Health and Human Health and Development; Department of Health
and Human Services [U10 HD21385, U10 HD40689, U10 HD27871, U10 HD21373,
U01 HD36790, U10 HD40498, U10 HD40461, U10 HD34216, U10 HD21397, U10
HD27904, U10 HD40492, U10 HD27856, U10 HD40521, U10 HD27853, U10
HD27880, U10 HD27851]; National Institutes of Health [GCRC M01 RR 08084,
M01 RR 00125, M01 RR 00750, M01 RR 00070, M01 RR 0039-43, M01 RR 00039,
5 M01 RR00044]
FX The National Institutes of Health and the Eunice Kennedy Shriver
National Institute of Child Health and Human Health and Development
provided grant support for the NRN's benchmarking study (recruitment
March 1, 2001, to April 30, 2004) and generic database study
(recruitment January to December 2006). This work was supported by
grants from the Eunice Kennedy Shriver National Institute of Child
Health and Human Health and Development and the Department of Health and
Human Services (U10 HD21385, U10 HD40689, U10 HD27871, U10 HD21373, U01
HD36790, U10 HD40498, U10 HD40461, U10 HD34216, U10 HD21397, U10
HD27904, U10 HD40492, U10 HD27856, U10 HD40521, U10 HD27853, U10
HD27880, U10 HD27851) and from the National Institutes of Health (GCRC
M01 RR 08084, M01 RR 00125, M01 RR 00750, M01 RR 00070, M01 RR 0039-43,
M01 RR 00039, and 5 M01 RR00044). Data collected at participating sites
of the Eunice Kennedy Shriver National Institute of Child Health and
Human Health and Development NRN were transmitted to RTI International,
the data coordinating center for the network, which stored, managed and
analyzed the data for this study. On behalf of the NRN, Drs Abhik Das
(data coordinating center principal investigator) and Georgiy Bobashev
(data coordinating center statistician) had full access to all the data
in the study and take responsibility for the integrity of the data and
accuracy of the data analysis.; The following investigators, in addition
to those listed as authors, participated in this study (National
Institutes of Health grant numbers are listed also): NRN chair: Alan
Jobe, MD PhD, University of Cincinnati; Cincinnati Children's Hospital
Medical Center, University of Cincinnati Hospital and Good Samaritan
Hospital (GCRC M01 RR8084, U10 HD27853): Edward F. Donovan, MD, Kurt
Schibler, MD, Kathleen Bridges, MD, Barbara Alexander, RN, Cathy Grisby,
BSN, CCRC, Jody Hessling, RN, Holly L. Mincey, RN, BSN, and Marcia
Worley Mersmann, RN, CCRC; Duke University School of Medicine University
Hospital, Alamance Regional Medical Center, and Durham Regional Hospital
(GCRC M01 RR30, U10 HD40492): Ronald N. Goldberg, MD, C. Michael Cotten,
MD, MHS, and Kathy Auten, MSHS; Emory University Children's Health Care
of Atlanta, Grady Memorial Hospital, and Emory Crawford Long Hospital
(GCRC M01 RR39, U10 HD27851): Barbara J. Stoll, MD, Susie Buchter, MD,
Ellen C. Hale, R, RN, BS, CCRC; Eunice Kennedy Shriver National
Institute of Child Health and Human Development: Linda L. Wright, MD,
Rosemary D. Higgins, MD, Elizabeth M. McClure, Med; Indiana University
Indiana University Hospital, Methodist Hospital, Riley Hospital for
Children, and Wishard Health Services (GCRC M01 RR750, U10 HD27856):
James A. Lemons, MD, Brenda B. Poindexter, MD, MS, William A. Engle, MD,
Diana D. Appel, RN, BSN, Dianne Herron, RN, Lucy Miller, RN, BSN, CCRC,
Richard Hooper, RRT; Rainbow Babies & Children's Hospital (GCRC M01
RR80, U10 HD21364): Avroy A. Fanaroff, MD, Nancy S. Newman, RN; RTI
International (U01 HD36790): W. Kenneth Poole, PhD, Betty Hastings,
Elizabeth McClure, Med, Qing Yao, PhD, Jeanette O'Donnell Auman, BS,
Carolyn Petrie Huitema, MS, Scott E. Schaefer, MS, Kristin M.
Zaterka-Baxter, RN; Stanford University Lucile Packard Children's
Hospital (GCRC M01 RR70, U10 HD27880): David K. Stevenson, MD, Krisa P.
Van Meurs, MD, William D. Rhine, MD, M. Bethany Ball, BS, CCRC, Carol
Kibler, RN, Jeffrey R. Parker, RRT; Tufts Medical Center Floating
Hospital for Children (GCRC M01 RR54, U10 HD53119): Ivan D. Frantz, III,
MS, Brenda L. MacKinnon, RNC, Ellen Nylen, RN, University of Alabama at
Birmingham Health System and Children's Hospital of Alabama (GCRC M01
RR32, U10 HD34216): Monica V. Collins, RN, BSN, MaEd, Shirley S. Cosby,
RN, BSN; University of California, San Diego Medical Center and Sharp
Mary Birch Hospital for Women (U10 HD40461): Neil N. Finer, MD, Maynard
R. Rasmussen, MD, Paul R. Wozniak, MD, Greg Heldt, MD, Kathy Arnell,
RNC, Clarence Demetrio, RN, Chris Henderson, RCP, CRTT, Wade Rich, BSHS,
RRT, Mindy Grabarczyk, BSN, Christina Joseph, RRT, Renee Bridge, RN, Jim
Goodmar, RRT; University of Iowa Children's Hospital (GCRC M01 RR59, U10
HD53109): Edward F. Bell, MD, Karen J. Johnson, RN, BSN; University of
Miami Holtz Children's Hospital (GCRC M01 RR16587, U10 HD21397): Shahnaz
Duara, MD, Ruth Everett-Thomas, RN, MSN; University of New Mexico Health
Sciences Center (GCRC M01 RR997, U10 HD53089): Kristi L. Watterberg, MD,
Conra Backstrom Lacy, RN; University of Rochester Golisano Children's
Hospital at Strong (GCRC M01 RR44, U10 HD40521): Dale L. Phelps, MD,
Robert A. Sinkin, MD, Linda Reubens, RN; University of Texas
Southwestern Medical Center at Dallas Parkland Health & Hospital System
and Children's Medical Center Dallas (GCRC M01 RR633, U10 HD40689):
Abbot R. Laptook, MD, Walid A. Salhab, MD, Charles R. Rosenfeld, MD,
Pablo J. Sanchez, MD, James Allen, RRT, Alicia Guzman, Gay Hensley, RN,
Susie Madison, RN, Melissa Martin, RN, Nancy A.; Miller, RN; niversity
of Texas Health Science Center at Houston, Medical School, Children's
Memorial Hermann Hospital, and Lydon Baines Johnson General Hospital
(U10 HD21373): Jon E. Tyson, MD, MPH, Kathleen A. Kennedy, MD, MPH,
Esther G. Akpa, RN, BSN, Patty A. Cluff, RN, Claudia I. Franco, RNC,
MSN, Anna E. Lis, RN, BSN, Georgia E. McDavid, RN, Nora I. Alaniz, BS,
Patti Pierce Tate, RCP, University of Utah University Hospital, LDS
Hospital, and Primary Children's Medical Center (GCRC M01 RR64, U10
HD53124): Roger G. Faix, MD, Bradley A. Yoder, MD, Karen A. Osborne, RN,
BSN, Jennifer J. Jensen, RN, BSN, Wake Forest University Baptist Medical
Center, Brenner Children's Hospital, and Forsyth Medical Center (GCRC
M01 RR7122, U10 HD40498): T. Michael O'Shea, MD, MPH, Nancy J. Peters,
RN, CCRP; Wayne State University Hutzel Women's Hospital and Children's
Hospital of Michigan (U10 HD21385): Seetha Shankaran, MD, Rebecca Bara,
RN, BSN, Geraldine Muran, RN, BSN, S. Nadya Kazzi, MD, MPH, Kimberly
Hayes-Hart, RN, MSN, NNP-BC, Maria Batts, RRT; Women & Infants Hospital
of Rhode Island (U10 HD27904): William Oh, MD, Abbot R. Laptook, MD,
Angelita Hensman, BSN, RNC; Yale University Yale-New Haven Children's
Hospital (GCRC M01 RR125, GCRC M01 RR6022, U10 HD27871): Richard A.
Ehren-kranz, MD, Patricia Gettner, RN, Monica Konstantino, RN, BSN,
JoAnn Poulsen, RN.
NR 18
TC 34
Z9 34
U1 2
U2 4
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
J9 PEDIATRICS
JI Pediatrics
PD JAN
PY 2011
VL 127
IS 1
BP E106
EP E116
DI 10.1542/peds.2010-0648
PG 11
WC Pediatrics
SC Pediatrics
GA 700YT
UT WOS:000285782200014
PM 21149431
ER
PT B
AU Franquelim, HG
Matos, PM
Veiga, AS
AF Franquelim, Henri G.
Matos, Pedro M.
Salome Veiga, A.
BE Castanho, M
Santos, NC
TI HIV vs. HIV: Turning HIV-Derived Peptides into Drugs
SO PEPTIDE DRUG DISCOVERY AND DEVELOPMENT: TRANSLATIONAL RESEARCH IN
ACADEMIA AND INDUSTRY
LA English
DT Article; Book Chapter
ID IMMUNODEFICIENCY-VIRUS TYPE-1; FUSION INHIBITOR PEPTIDES; HEPTAD REPEAT
REGION; IN-VITRO SYNERGY; CELL-CELL FUSION; MEMBRANE-FUSION; ENTRY
INHIBITORS; ENVELOPE GLYCOPROTEIN; ANTIRETROVIRAL ACTIVITY; POTENT
INHIBITORS
C1 [Franquelim, Henri G.; Matos, Pedro M.; Salome Veiga, A.] Univ Lisbon, Inst Med Mol, Fac Med, P-1649028 Lisbon, Portugal.
[Salome Veiga, A.] NCI, Biol Chem Lab, Frederick, MD 21702 USA.
RP Franquelim, HG (reprint author), Univ Lisbon, Inst Med Mol, Fac Med, Av Prof Egas Moniz, P-1649028 Lisbon, Portugal.
OI Veiga, Ana Salome/0000-0002-9892-2243
NR 91
TC 1
Z9 1
U1 1
U2 1
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA PAPPELALLEE 3, W-69469 WEINHEIM, GERMANY
BN 978-3-527-63675-4; 978-3-527-32891-8
PY 2011
BP 209
EP 229
D2 10.1002/9783527636730
PG 21
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology &
Pharmacy
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA BA9PZ
UT WOS:000339712000011
ER
PT J
AU Nasr, S
Ungerleider, L
Tootell, R
AF Nasr, S.
Ungerleider, L.
Tootell, R.
TI Parallel streams recognition of face versus non-face objects in human
temporal lobe
SO PERCEPTION
LA English
DT Meeting Abstract
C1 [Ungerleider, L.] NIH, Bethesda, MD 20892 USA.
EM shahin@nmr.mgh.harvard.edu
NR 0
TC 0
Z9 0
U1 0
U2 1
PU PION LTD
PI LONDON
PA 207 BRONDESBURY PARK, LONDON NW2 5JN, ENGLAND
SN 0301-0066
J9 PERCEPTION
JI Perception
PY 2011
VL 40
SU S
BP 25
EP 25
PG 1
WC Ophthalmology; Psychology; Psychology, Experimental
SC Ophthalmology; Psychology
GA V27PI
UT WOS:000208624700079
ER
PT J
AU Arizpe, J
Kravitz, D
Yovel, G
Baker, C
AF Arizpe, J.
Kravitz, D.
Yovel, G.
Baker, C.
TI Differences in looking at own-race and other-race faces
SO PERCEPTION
LA English
DT Meeting Abstract
C1 [Arizpe, J.; Kravitz, D.; Baker, C.] NIMH, Bethesda, MD USA.
[Yovel, G.] Tel Aviv Univ, Tel Aviv, Israel.
EM bakerchris@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU PION LTD
PI LONDON
PA 207 BRONDESBURY PARK, LONDON NW2 5JN, ENGLAND
SN 0301-0066
J9 PERCEPTION
JI Perception
PY 2011
VL 40
SU S
BP 155
EP 155
PG 1
WC Ophthalmology; Psychology; Psychology, Experimental
SC Ophthalmology; Psychology
GA V27PI
UT WOS:000208624700495
ER
PT J
AU Finkelstein, FO
Juergensen, P
Wang, SX
Santacroce, S
Levine, M
Kotanko, P
Levin, NW
Handelman, GJ
AF Finkelstein, Fredric O.
Juergensen, Peter
Wang, Suxin
Santacroce, Sally
Levine, Mark
Kotanko, Peter
Levin, Nathan W.
Handelman, Garry J.
TI HEMOGLOBIN AND PLASMA VITAMIN C LEVELS IN PATIENTS ON PERITONEAL
DIALYSIS
SO PERITONEAL DIALYSIS INTERNATIONAL
LA English
DT Article
DE Vitamin C; hemoglobin; anemia
ID CHRONIC-HEMODIALYSIS PATIENTS; INTRAVENOUS ASCORBIC-ACID;
DEHYDROASCORBIC ACID; IRON-ABSORPTION; DEFICIENCY; ERYTHROPOIETIN;
INFLAMMATION; FERRITIN; WOMEN; SUPPLEMENTATION
AB Objective: To determine the contribution of vitamin C (Vit C) status in relation to hemoglobin (Hb) levels in patients on long-term peritoneal dialysis (PD).
Methods: 56 stable PD patients were evaluated in a cross-sectional survey. Plasma samples were collected for Vit C (analyzed by HPLC with electrochemical detection) and high-sensitivity C-reactive protein (hs-CRP) determinations. Clinical records were reviewed for Hb, transferrin saturation (TSAT), ferritin, erythropoietin (EPO) dose, and other clinical parameters. Dietary Vit C intake was evaluated by patient survey and from patient records. Total Vit C removed during PD treatment was measured in 24-hour dialysate collections.
Results: Patients showed a highly skewed distribution of plasma Vit C levels, with 40% of patients below normal plasma Vit C levels (<30 mu mol/L) and 9% at higher than normal levels (>80 mu mol/L). Higher plasma Vit C levels were associated with higher Hb levels (Pearson r = 0.33, p < 0.004). No direct connection between Vit C levels and reported dietary intake could be established. In stepwise multiple regression, plasma Vit C remained significantly associated with Hb (p = 0.017) but there was no significant association with other variables (dialysis vintage, age, ferritin, TSAT, hs-CRP, residual renal function, and EPO dose). In 9 patients that were evaluated for Vit C in dialysate, plasma Vit C was positively associated (Spearman r = 0.85, p = 0.01) with the amount of Vit C removed during dialysis treatment.
Conclusions: These data indicate that plasma Vit C is positively associated with higher Hb level. Vit C status could play a major role in helping PD patients to utilize iron for erythropoiesis and achieve a better Hb response during anemia management.
C1 [Handelman, Garry J.] Univ Massachusetts, Clin Lab Sci & Nutr, Lowell, MA 01854 USA.
[Finkelstein, Fredric O.; Juergensen, Peter; Santacroce, Sally] New Haven CAPD, New Haven, CT USA.
[Finkelstein, Fredric O.] Hosp St Raphael, New Haven, CT 06511 USA.
[Finkelstein, Fredric O.] Yale Univ, New Haven, CT USA.
[Levine, Mark] NIDDK, NIH, Bethesda, MD USA.
[Kotanko, Peter; Levin, Nathan W.; Handelman, Garry J.] Renal Res Inst, New York, NY USA.
RP Handelman, GJ (reprint author), Univ Massachusetts, Clin Lab Sci & Nutr, 3 Solomont Way, Lowell, MA 01854 USA.
EM garry_handelman@uml.edu
FU Renal Research Institute
FX Financial support was provided by a gift from the Renal Research
Institute.
NR 38
TC 8
Z9 9
U1 1
U2 3
PU MULTIMED INC
PI TORONTO
PA 66 MARTIN ST, TORONTO, ON L9T 2R2, CANADA
SN 0896-8608
J9 PERITON DIALYSIS INT
JI Perit. Dial. Int.
PD JAN-FEB
PY 2011
VL 31
IS 1
BP 74
EP 79
DI 10.3747/pdi.2009.00154
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA 713HN
UT WOS:000286726800014
PM 20558814
ER
PT J
AU DeBono, A
Shmueli, D
Muraven, M
AF DeBono, Amber
Shmueli, Dikla
Muraven, Mark
TI Rude and Inappropriate: The Role of Self-Control in Following Social
Norms
SO PERSONALITY AND SOCIAL PSYCHOLOGY BULLETIN
LA English
DT Article
DE norms; self-regulation; self-control; self; morality; individual
differences
ID HIRSCHIS GENERAL-THEORY; LIMITED RESOURCES; CONTROL STRENGTH;
EMPIRICAL-TEST; CRIME; DEPLETION; GOTTFREDSON; EMOTIONALITY; DETERRENCE;
MANAGEMENT
AB Following social norms to avoid deviant or socially inappropriate behavior may require self-control. This was tested in two experiments that experimentally manipulated individuals' level of self-control strength. In the first experiment, individuals whose self-control capacity was depleted were more likely to misrepresent how many problems they solved and work after being told to stop while working on a timed test. These same results were found in individuals low in trait self-control. This was especially true when the certainty of getting caught was low. In the second experiment, depleted individuals were ruder to the experimenter than nondepleted participants. The results have implications for understanding how self-control contributes to normative behavior.
C1 [DeBono, Amber; Muraven, Mark] SUNY Albany, Albany, NY 12065 USA.
[Shmueli, Dikla] NCI, Bathesda, MD USA.
RP DeBono, A (reprint author), SUNY Albany, 1400 Washington Ave, Albany, NY 12065 USA.
EM amberdebono@yahoo.com
RI Muraven, Mark/A-5725-2009
OI Muraven, Mark/0000-0003-3057-4323
FU NIAAA NIH HHS [AA12770]; NIDA NIH HHS [DA015131]
NR 41
TC 14
Z9 16
U1 3
U2 24
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0146-1672
J9 PERS SOC PSYCHOL B
JI Pers. Soc. Psychol. Bull.
PD JAN
PY 2011
VL 37
IS 1
BP 136
EP 146
DI 10.1177/0146167210391478
PG 11
WC Psychology, Social
SC Psychology
GA 697UP
UT WOS:000285544600011
PM 21177879
ER
PT S
AU Barchi, JJ
AF Barchi, Joseph J., Jr.
BE Huang, X
Barchi, JJ
TI Glyco-Nanoparticles as Platforms for Antitumor Therapeutic Strategies
SO PETITE AND SWEET: GLYCO-NANOTECHNOLOGY AS A BRIDGE TO NEW MEDICINES
SE ACS Symposium Series
LA English
DT Proceedings Paper
CT Symposium on Petite and Sweet: Glyco-Nanotechnology as a Bridge to New
Medicines
CY AUG 22-26, 2010
CL Boston, MA
SP GP BioSciences, Omicron, ACS, Div Carbohydrate Chem
ID THOMSEN-FRIEDENREICH DISACCHARIDE; CARBOHYDRATE-CARBOHYDRATE
INTERACTIONS; ENTRAPPED GOLD NANOPARTICLES; VACCINE DELIVERY-SYSTEMS;
CANCER-THERAPY; IMMUNE-RESPONSES; BIOMEDICAL APPLICATIONS; DENDRITIC
CELLS; IN-VITRO; MAGNETIC GLYCONANOPARTICLES
AB There has been an explosion of progress in the development of novel nanotechnology-based platforms for a variety of applications. One reason for this development is that the properties of nanomaterials (optical, scattering, physical) can be dramatically different than those of macro-based technologies. Many of these unique properties can be exploited to develop novel imaging agents and delivery systems. A host of biologically relevant molecules can be conjugated to nanoparticles to functionalize these platforms. Cellular glycans are one family of biomolecules that have been coated on different nanoparticle platforms and some of these tools are being successfully employed for specific biomedical applications. To date however, the application of these so-called glyconanoparticles for antitumor therapeutics has been sparse. Fortunately, some initial results with glyconanoparticles have been very encouraging for possible translation to clinically relevant anti-tumor therapies. This chapter will examine the most recent work reported on the synthesis, development and application of the most promising platforms.
C1 NCI, Biol Chem Lab, Mol Discovery Program, Ctr Canc Res, Frederick, MD 21702 USA.
RP Barchi, JJ (reprint author), NCI, Biol Chem Lab, Mol Discovery Program, Ctr Canc Res, Frederick, MD 21702 USA.
EM barchi@helix.nih.gov
RI Barchi Jr., Joseph/N-3784-2014
NR 128
TC 4
Z9 4
U1 3
U2 14
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA
SN 0097-6156
BN 978-0-8412-2688-3
J9 ACS SYM SER
JI ACS Symp. Ser.
PY 2011
VL 1091
BP 161
EP 179
PG 19
WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology
SC Biotechnology & Applied Microbiology; Science & Technology - Other
Topics
GA BDF52
UT WOS:000313021800010
ER
PT J
AU Frohlich, H
Boini, KM
Seebohm, G
Strutz-Seebohm, N
Ureche, ON
Foller, M
Eichenmuller, M
Shumilina, E
Pathare, G
Singh, AK
Seidler, U
Pfeifer, KE
Lang, F
AF Froehlich, Henning
Boini, Krishna M.
Seebohm, Guiscard
Strutz-Seebohm, Nathalie
Ureche, Oana N.
Foeller, Michael
Eichenmueller, Melanie
Shumilina, Ekaterina
Pathare, Ganesh
Singh, Anurag Kumar
Seidler, Ursula
Pfeifer, Karl E.
Lang, Florian
TI Hypothyroidism of gene-targeted mice lacking Kcnq1
SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
LA English
DT Article
DE K(+) channels; Body temperature; Thyroid hormones; T3/T4; TSH; KCNE;
Chromanol
ID POTASSIUM CHANNEL; PARIETAL-CELLS; ION CHANNELS; K+ CHANNELS; MEMBRANE;
KVLQT1; VOLUME; EXPRESSION; PROTEIN; RAT
AB Thyroid hormones T3/T4 participate in the fine tuning of development and performance. The formation of thyroid hormones requires the accumulation of I(-) by the electrogenic Na(+)/I(-) symporter, which depends on the electrochemical gradient across the cell membrane and thus on K(+) channel activity. The present paper explored whether Kcnq1, a widely expressed voltage-gated K(+) channel, participates in the regulation of thyroid function. To this end, Kcnq1 expression was determined by RT-PCR, confocal microscopy, and thyroid function analyzed in Kcnq1 deficient mice (Kcnq1(-/-)) and their wild-type littermates (Kcnq1(+/+)). Moreover, Kcnq1 abundance and current were determined in the thyroid FRTL-5 cell line. Furthermore, mRNA encoding KCNQ1 and the subunits KCNE1-5 were discovered in human thyroid tissue. According to patch-clamp TSH (10 mUnits/ml) induced a voltage-gated K(+) current in FRTL-5 cells, which was inhibited by the Kcnq inhibitor chromanol (10 mu M). Despite a tendency of TSH plasma concentrations to be higher in Kcnq1(-/-) than in Kcnq1(+/+) mice, the T3 and T4 plasma concentrations were significantly smaller in Kcnq1(-/-) than in Kcnq1(+/+) mice. Moreover, body temperature was significantly lower in Kcnq1(-/-) than in Kcnq1(+/+) mice. In conclusion, Kcnq1 is required for proper function of thyroid glands.
C1 [Froehlich, Henning; Boini, Krishna M.; Ureche, Oana N.; Foeller, Michael; Eichenmueller, Melanie; Shumilina, Ekaterina; Pathare, Ganesh; Lang, Florian] Univ Tubingen, Dept Physiol, D-72076 Tubingen, Germany.
[Seebohm, Guiscard; Strutz-Seebohm, Nathalie] Ruhr Univ Bochum, Dept Biochem 1, D-44780 Bochum, Germany.
[Ureche, Oana N.] Univ Tubingen, Dept Mol Pathol, D-72076 Tubingen, Germany.
[Singh, Anurag Kumar; Seidler, Ursula] Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, D-30625 Hannover, Germany.
[Pfeifer, Karl E.] NICHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD USA.
RP Lang, F (reprint author), Univ Tubingen, Dept Physiol, Gmelinstr 5, D-72076 Tubingen, Germany.
EM florian.lang@uni-tuebingen.de
RI Boini, Krishna/H-3548-2011;
OI Pfeifer, Karl/0000-0002-0254-682X
FU Deutsche Forschungsgemeinschaft [GK 1302, Se460/9-6]
FX The authors acknowledge the technical assistance of E. Faber, R.
Engelhardt, B. Rausch, and Dr. B. Riederer for breeding and genotyping
kcnq1-/- and kcnq1+/+ mice. The manuscript was
meticulously prepared by T. Loch and L. Subasic. This study was
supported by the Deutsche Forschungsgemeinschaft (GK 1302) and Se460/9-6
(to U.S.).
NR 43
TC 14
Z9 14
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0031-6768
J9 PFLUG ARCH EUR J PHY
JI Pflugers Arch.
PD JAN
PY 2011
VL 461
IS 1
BP 45
EP 52
DI 10.1007/s00424-010-0890-5
PG 8
WC Physiology
SC Physiology
GA 710KX
UT WOS:000286511600004
PM 20978783
ER
PT J
AU Yao, MY
Roberts, DD
Isenberg, JS
AF Yao, Mingyi
Roberts, David D.
Isenberg, Jeff S.
TI Thrombospondin-1 inhibition of vascular smooth muscle cell responses
occurs via modulation of both cAMP and cGMP
SO PHARMACOLOGICAL RESEARCH
LA English
DT Article
DE cAMP; cGMP; Thrombospondin-1; Vascular smooth muscle cells
ID ISCHEMIC TISSUE SURVIVAL; NITRIC-OXIDE; CARDIOVASCULAR-SYSTEM;
SIGNAL-TRANSDUCTION; CYCLIC-GMP; MYOSIN PHOSPHORYLATION;
ADENYLATE-CYCLASE; CHEMOTAXIS; RELAXATION; PHOSPHODIESTERASE-3
AB Nitric oxide (NO) drives pro-survival responses in vascular cells and limits platelet adhesion, enhancing blood flow and minimizing thrombosis. The matricellular protein thrombospondin-1 (TSP1), through interaction with its receptor CD47, inhibits soluble guanylyl cyclase (sGC) activation by NO in vascular cells. In vascular smooth muscle cells (VSMCs) both intracellular cGMP and cAMP regulate adhesion, contractility, proliferation, and migration. cGMP can regulate cAMP through feedback control of hydrolysis. Inhibition of the cAMP phosphodiesterase-4 selectively interfered with the ability of exogenous TSP1 to block NO-driven VSMC adhesion but not cGMP accumulation, suggesting that cAMP also contributes to VSMC regulation by TSP1. Inhibition of phosphodiesterase-4 was sufficient to elevate cAMP levels, and inhibiting guanylyl cyclase or phosphodiesterase-3, or adding exogenous TSP1 reversed this increase in cAMP. Thus, TSP1 regulates VSMC cAMP levels in part via cGMP-dependent inhibition of phosphodiesterase-3. Additionally basal cAMP levels were consistently elevated in both VSMCs and skeletal muscle from TSP1 null mice, and treating null cells with exogenous TSP1 suppressed cAMP levels to those of wild type cells. TSP1 inhibited both forskolin and isoproterenol stimulated increases in cAMP in VSMCs. TSP1 also abrogated forskolin and isoproterenol stimulated vasodilation. Consistent with its ability to directly limit adenylyl cyclase-activated vasodilation, TSP1 also limited cAMP-induced dephosphorylation of myosin light chain-2. These findings demonstrate that TSP1 limits both cGMP and cAMP signaling pathways and functional responses in VSMCs and arteries, by both phosphodiesterase-dependent cross talk between these second messengers and by inhibition of adenylyl cyclase activation. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Yao, Mingyi; Isenberg, Jeff S.] Univ Pittsburgh, Vasc Med Inst, Pittsburgh, PA 15261 USA.
[Isenberg, Jeff S.] Univ Pittsburgh, Div Pulm Allergy & Crit Care Med, Sch Med, Pittsburgh, PA 15261 USA.
[Roberts, David D.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Isenberg, JS (reprint author), Univ Pittsburgh, Vasc Med Inst, 10048 Biomed Sci Tower 3,3501 5th Ave, Pittsburgh, PA 15261 USA.
EM jsi5@pitt.edu
RI Roberts, David/A-9699-2008
OI Roberts, David/0000-0002-2481-2981
FU NIH [K22 CA128616]; NIH, National Cancer Institute, Center for Cancer
Research
FX This research was supported by the following funding: NIH grant K22
CA128616 (JSI) and the Intramural Research Program of the NIH, National
Cancer Institute, Center for Cancer Research (DDR).
NR 56
TC 20
Z9 20
U1 0
U2 4
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-6618
J9 PHARMACOL RES
JI Pharmacol. Res.
PD JAN
PY 2011
VL 63
IS 1
BP 13
EP 22
DI 10.1016/j.phrs.2010.10.014
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 722HH
UT WOS:000287422800003
PM 20971192
ER
PT J
AU Laskin, J
Yang, ZB
Woods, AS
AF Laskin, Julia
Yang, Zhibo
Woods, Amina S.
TI Competition between covalent and noncovalent bond cleavages in
dissociation of phosphopeptide-amine complexes
SO PHYSICAL CHEMISTRY CHEMICAL PHYSICS
LA English
DT Article
ID SURFACE-INDUCED DISSOCIATION; NEGATIVE-ION FRAGMENTATIONS; RESONANCE
MASS-SPECTROMETRY; PROTEIN-LIGAND COMPLEXES; CLUSTER-PHASE REACTIONS;
GAS-PHASE; PEPTIDE IONS; VANCOMYCIN ANTIBIOTICS; DEPROTONATED PEPTIDES;
AMAZING STABILITY
AB Interactions between quaternary amino or guanidino groups with anions are ubiquitous in nature and have been extensively studied phenomenologically. However, little is known about the binding energies in non-covalent complexes containing these functional groups. Here, we present a first study focused on quantifying such interactions using complexes of phosphorylated A(3)pXA(3)-NH2 (X = S, T, Y) peptides with decamethonium (DCM) or diaguanidinodecane (DGD) ligands as model systems. Time-and collision energy-resolved surface-induced dissociation (SID) of the singly charged complexes was examined using a specially configured Fourier transform ion cyclotron resonance mass spectrometer (FTICR-MS). Dissociation thresholds and activation energies were obtained from RRKM modeling of the experimental data that has been described and carefully characterized in our previous studies. For systems examined in this study, covalent bond cleavages resulting in phosphate abstraction by the cationic ligand are characterized by low dissociation thresholds and relatively tight transition states. In contrast, high dissociation barriers and large positive activation entropies were obtained for cleavages of non-covalent bonds. Dissociation parameters obtained from the modeling of the experimental data are in excellent agreement with the results of density functional theory (DFT) calculations. Comparison between the experimental data and theoretical calculations indicate that phosphate abstraction by the ligand is rather localized and mainly affected by the identity of the phosphorylated side chain. The hydrogen bonding in the peptide and ligand properties play a minor role in determining the energetics and dynamics of the phosphate abstraction channel.
C1 [Laskin, Julia; Yang, Zhibo] Pacific NW Natl Lab, Chem & Mat Sci Div, Richland, WA 99352 USA.
[Woods, Amina S.] NIDA IRP, Struct Biol Unit, Cellular Neurobiol Branch, NIH, Baltimore, MD 21224 USA.
RP Laskin, J (reprint author), Pacific NW Natl Lab, Chem & Mat Sci Div, POB 999,K8-88, Richland, WA 99352 USA.
EM Julia.Laskin@pnl.gov
RI Laskin, Julia/H-9974-2012
OI Laskin, Julia/0000-0002-4533-9644
FU W. R. Wiley Environmental Molecular Sciences Laboratory (EMSL); Division
of Chemical Sciences, Geosciences, and Biosciences, Office of Basic
Energy Sciences of the U. S. Department of Energy (DOE); National
Institute on Drug Abuse, NIH; DOE's Office of Biological and
Environmental Research; U. S. Department of Energy [DE-AC05-76RL01830]
FX This study was partially supported by the W. R. Wiley Environmental
Molecular Sciences Laboratory (EMSL) user program, by a grant from the
Division of Chemical Sciences, Geosciences, and Biosciences, Office of
Basic Energy Sciences of the U. S. Department of Energy (DOE), and by
the Intramural Research Program of the National Institute on Drug Abuse,
NIH. The research described in this manuscript was performed using EMSL,
a national scientific user facility sponsored by the DOE's Office of
Biological and Environmental Research and located at Pacific Northwest
National Laboratory (PNNL). PNNL is operated by Battelle for the U. S.
Department of Energy under contract DE-AC05-76RL01830.
NR 57
TC 7
Z9 7
U1 0
U2 16
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 1463-9076
EI 1463-9084
J9 PHYS CHEM CHEM PHYS
JI Phys. Chem. Chem. Phys.
PY 2011
VL 13
IS 15
BP 6936
EP 6946
DI 10.1039/c1cp00029b
PG 11
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 742NL
UT WOS:000288951000020
PM 21387029
ER
PT J
AU Lu, C
Chen, Z
Yu, P
AF Lu, Chi
Chen, Zhi
Yu, Ping
TI A novel reaction model for the electrical conductivity of ultra-thin
TiO2 films in H-2
SO PHYSICAL CHEMISTRY CHEMICAL PHYSICS
LA English
DT Article
ID METAL-SUPPORT INTERACTIONS; HYDROGEN SPILLOVER; ALUMINUM-OXIDE;
CATALYSTS; TITANIA; OXIDATION
AB Two ultra-thin TiO2 films with platinum electrodes were prepared on a porous anodic aluminium oxide thick layer and a ceramic plate, respectively. It was found that in both TiO2 films the conductance was almost proportional to the fourth root of the H-2 concentration in N-2 ambient at 500 degrees C. A quantitative model based on the spill-over mechanism is established to describe this novel correlation.
C1 [Lu, Chi; Chen, Zhi] Univ Kentucky, Dept Elect & Comp Engn, Lexington, KY 40506 USA.
[Lu, Chi; Chen, Zhi] Univ Kentucky, Ctr Nanoscale Sci & Engn, Lexington, KY 40506 USA.
[Yu, Ping] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA.
RP Lu, C (reprint author), Univ Kentucky, Dept Elect & Comp Engn, Lexington, KY 40506 USA.
EM chi_lu_uky@yahoo.com
OI Chen, Zhi/0000-0002-4451-5626
FU Department of Energy [DE-FG26-04NT42171]; National Science Foundation of
the USA [ECS-0609064]
FX This work was supported in part by the Department of Energy
(DE-FG26-04NT42171) and National Science Foundation (ECS-0609064) of the
USA. We appreciate the editorial assistance of the NIH Fellows Editorial
Board.
NR 22
TC 4
Z9 4
U1 0
U2 7
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 1463-9076
J9 PHYS CHEM CHEM PHYS
JI Phys. Chem. Chem. Phys.
PY 2011
VL 13
IS 20
BP 9131
EP 9133
DI 10.1039/c1cp20180h
PG 3
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 759FA
UT WOS:000290224900006
PM 21503315
ER
PT J
AU Swierczewska, M
Lee, S
Chen, XY
AF Swierczewska, Magdalena
Lee, Seulki
Chen, Xiaoyuan
TI The design and application of fluorophore-gold nanoparticle activatable
probes
SO PHYSICAL CHEMISTRY CHEMICAL PHYSICS
LA English
DT Article
ID RESONANCE ENERGY-TRANSFER; IN-VIVO; QUANTUM DOTS; ENHANCED FLUORESCENCE;
RHEUMATOID-ARTHRITIS; METALLIC NANOCAVITY; CONJUGATED POLYMERS;
MOLECULAR BEACONS; CELLS; DECAY
AB Fluorescence-based assays and detection techniques are among the most highly sensitive and popular biological tests for researchers. To match the needs of research and the clinic, detection limits and specificities need to improve, however. One mechanism is to decrease non-specific background signals, which is most efficiently done by increasing fluorescence quenching abilities. Reports in the literature of theoretical and experimental work have shown that metallic gold surfaces and nanoparticles are ultra-efficient fluorescence quenchers. Based on these findings, subsequent reports have described gold nanoparticle fluorescence-based activatable probes that were designed to increase fluorescence intensity based on a range of stimuli. In this way, these probes can detect and signify assorted biomarkers and changes in environmental conditions. In this review, we explore the various factors and theoretical models that affect gold nanoparticle fluorescence quenching, explore current uses of activatable probes, and propose an engineering approach for future development of fluorescence based gold nanoparticle activatable probes.
C1 [Swierczewska, Magdalena; Lee, Seulki; Chen, Xiaoyuan] NIBIB, NIH, LOMIN, Bethesda, MD 20892 USA.
[Swierczewska, Magdalena] SUNY Stony Brook, Dept Biomed Engn, Stony Brook, NY 11794 USA.
RP Lee, S (reprint author), NIBIB, NIH, LOMIN, Bethesda, MD 20892 USA.
EM Seulki.Lee@nih.gov; Shawn.Chen@nih.gov
FU National Institute of Biomedical Imaging and Bioengineering (NIBIB);
NIH; National Science Foundation of China (NSFC) [81028009]
FX This work was supported in part by the Intramural Research Program (IRP)
of the National Institute of Biomedical Imaging and Bioengineering
(NIBIB), NIH and the International Cooperative Program of the National
Science Foundation of China (NSFC) (81028009). We thank Dr Henry S. Eden
for proofreading the manuscript.
NR 74
TC 72
Z9 72
U1 8
U2 60
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 1463-9076
J9 PHYS CHEM CHEM PHYS
JI Phys. Chem. Chem. Phys.
PY 2011
VL 13
IS 21
BP 9929
EP 9941
DI 10.1039/c0cp02967j
PG 13
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 765TR
UT WOS:000290732000003
PM 21380462
ER
PT J
AU Revilla-Lopez, G
Torras, J
Nussinov, R
Aleman, C
Zanuy, D
AF Revilla-Lopez, Guillem
Torras, Juan
Nussinov, Ruth
Aleman, Carlos
Zanuy, David
TI Exploring the energy landscape of a molecular engineered analog of a
tumor-homing peptide
SO PHYSICAL CHEMISTRY CHEMICAL PHYSICS
LA English
DT Article
ID CONFORMATIONAL PREFERENCES; AMINO-ACIDS; SOLVATION MODEL; SIDE-CHAIN;
DYNAMICS; PROTEINS; DESIGN; PENTAPEPTIDE; SIMULATIONS; PACLITAXEL
AB Recently a new non-coded amino acid was designed as a replacement for Arg, to protect the tumor-homing pentapeptide CREKA (Cys-Arg-Glu-Lys-Ala) from proteases. This constrained Arg analog, denoted c(5)Arg, was engineered to also promote the stability of the CREKA bioactive conformation. The conformational profile of the CREKA analog obtained by replacing Arg by c(5)Arg has been extensively investigated in this work. Two molecular dynamics simulations-based strategies have been employed: a modified simulated annealing and replica exchange. Results obtained using both techniques show that the conformational features of the new analog fulfill the purpose of its design. The new CREKA analog not only preserves the main structural attributes found for the bioactive conformation of the parent peptide but also shows lower flexibility. Moreover, the conformational profile of the mutated peptide narrows towards the most stable structures previously observed for the parent CREKA peptide.
C1 [Revilla-Lopez, Guillem; Aleman, Carlos; Zanuy, David] Univ Politecn Cataluna, Dept Engn Quim, ETS Engn Ind Barcelona, E-08028 Barcelona, Spain.
[Torras, Juan] Univ Politecn Cataluna, EEI, Dept Engn Quim, Igualada 08700, Spain.
[Nussinov, Ruth] NCI, Ctr Canc Res, Nanobiol Program, Basic Sci Program,SAIC Frederick Inc, Frederick, MD 21702 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sch Med, Dept Human Genet Sackler, IL-69978 Tel Aviv, Israel.
[Aleman, Carlos] Univ Politecn Cataluna, Ctr Res Nanoengn, E-08028 Barcelona, Spain.
RP Zanuy, D (reprint author), Univ Politecn Cataluna, Dept Engn Quim, ETS Engn Ind Barcelona, Diagonal 647, E-08028 Barcelona, Spain.
EM joan.torras@upc.edu; david.zanuy@upc.edu
RI Revilla-Lopez, Guillem/G-8552-2011; Zanuy, David/G-3930-2014; Torras,
Juan/F-5622-2015
OI Zanuy, David/0000-0001-7704-2178; Torras, Juan/0000-0001-8737-7609
FU Generalitat de Catalunya [SGR 925]; National Cancer Institute, National
Institutes of Health [HHSN261200800001E]; NIH, National Cancer
Institute, Center for Cancer Research
FX Computer resources were generously provided by the Centre de
Supercomputacio de Catalunya (CESCA), the National Cancer Institute for
partial allocation of computing time and staff support at the Advanced
Biomedical Computing Center of the Frederick Cancer Research and
Development Center and the high-performance computational capabilities
of the Biowulf PC/Linux cluster at the National Institutes of Health,
Bethesda, MD (http://biowulf.nih.gov). Financial support from
Generalitat de Catalunya (research group 2009 SGR 925; XRQTC; ICREA
Academia prize for excellence in research to C. A.) is gratefully
acknowledged. This project has been funded in part with Federal funds
from the National Cancer Institute, National Institutes of Health, under
contract number HHSN261200800001E. The content of this publication does
not necessarily reflect the view of the policies of the Department of
Health and Human Services, nor does mention of trade names, commercial
products, or organization imply endorsement by the U.S. Government. This
research was supported [in part] by the Intramural Research Program of
the NIH, National Cancer Institute, Center for Cancer Research.
NR 40
TC 4
Z9 4
U1 1
U2 7
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 1463-9076
J9 PHYS CHEM CHEM PHYS
JI Phys. Chem. Chem. Phys.
PY 2011
VL 13
IS 21
BP 9986
EP 9994
DI 10.1039/c0cp02572k
PG 9
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 765TR
UT WOS:000290732000009
PM 21258721
ER
PT J
AU Kaila, VRI
Hummer, G
AF Kaila, Ville R. I.
Hummer, Gerhard
TI Energetics and dynamics of proton transfer reactions along short water
wires
SO PHYSICAL CHEMISTRY CHEMICAL PHYSICS
LA English
DT Article
ID CYTOCHROME-C-OXIDASE; COUPLED ELECTRON-TRANSFER;
PARACOCCUS-DENITRIFICANS; MOLECULAR-DYNAMICS; RATE CONSTANTS; STRUCTURAL
DETERMINANTS; CORRELATION-ENERGY; CARBON NANOTUBES; EXCESS PROTON;
LIQUID WATER
AB Proton transfer (pT) reactions in biochemical processes are often mediated by chains of hydrogen-bonded water molecules. We use hybrid density functional calculations to study pT along quasi one-dimensional water arrays that connect an imidazolium-imidazole proton donor-acceptor pair. We characterize the structures of intermediates and transition states, the energetics, and the dynamics of the pT reactions, including vibrational contributions to kinetic isotope effects. In molecular dynamics simulations of pT transition paths, we find that for short water chains with four water molecules, the pT reactions are semi-concerted. The formation of a high-energy hydronium intermediate next to the proton-donating group is avoided by a simultaneous transfer of a proton from the donor to the first water molecule, and from the first water molecule into the water chain. Lowering the dielectric constant of the environment and increasing the water chain length both reduce the barrier for pT. We study the effect of the driving force on the energetics of the pT reaction by changing the proton affinity of the donor and acceptor groups through halogen and methyl substitutions. We find that the barrier of the pT reaction depends linearly on the proton affinity of the donor but is nearly independent of the proton affinity of the acceptor, corresponding to Bronsted slopes of one and zero, respectively.
C1 [Kaila, Ville R. I.; Hummer, Gerhard] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Kaila, VRI (reprint author), NIDDK, Chem Phys Lab, NIH, 5 Mem Dr, Bethesda, MD 20892 USA.
EM ville.kaila@nih.gov; gerhard.hummer@nih.gov
RI Hummer, Gerhard/A-2546-2013
OI Hummer, Gerhard/0000-0001-7768-746X
FU National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health; European Molecular Biology Organization
(EMBO)
FX We thank Dr. Jurgen Kofinger and Prof. Marten Wikstrom for insightful
discussions. This research was supported by the Intramural Research
Program of the National Institute of Diabetes and Digestive and Kidney
Diseases, National Institutes of Health. V. R. I. K. also acknowledges
the European Molecular Biology Organization (EMBO) for a Long-Term
Fellowship. CSC, the Finnish IT Center for Science, and Biowulf cluster
at NIH are acknowledged for computer time.
NR 88
TC 20
Z9 21
U1 0
U2 31
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 1463-9076
J9 PHYS CHEM CHEM PHYS
JI Phys. Chem. Chem. Phys.
PY 2011
VL 13
IS 29
BP 13207
EP 13215
DI 10.1039/c1cp21112a
PG 9
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 795NT
UT WOS:000292981600010
PM 21701719
ER
PT J
AU Kofinger, J
Hummer, G
Dellago, C
AF Koefinger, Juergen
Hummer, Gerhard
Dellago, Christoph
TI Single-file water in nanopores
SO PHYSICAL CHEMISTRY CHEMICAL PHYSICS
LA English
DT Article
ID BORON-NITRIDE NANOTUBES; MOLECULAR-DYNAMICS SIMULATIONS; SOLID-STATE
NANOPORES; CARBON NANOTUBES; PROTON TRANSPORT; LIQUID WATER;
ORIENTATIONAL DEFECTS; GRAMICIDIN CHANNEL; HYDRATED PROTON;
MASS-TRANSPORT
AB Water molecules confined to pores with sub-nanometre diameters form single-file hydrogen-bonded chains. In such nanoscale confinement, water has unusual physical properties that are exploited in biology and hold promise for a wide range of biomimetic and nanotechnological applications. The latter can be realized by carbon and boron nitride nanotubes which confine water in a relatively non-specific way and lend themselves to the study of intrinsic properties of single-file water. As a consequence of strong water-water hydrogen bonds, many characteristics of single-file water are conserved in biological and synthetic pores despite differences in their atomistic structures. Charge transport and orientational order in water chains depend sensitively on and are mainly determined by electrostatic effects. Thus, mimicking functions of biological pores with apolar pores and corresponding external fields gives insight into the structure-function relation of biological pores and allows the development of technical applications beyond the molecular devices found in living systems. In this Perspective, we revisit results for single-file water in apolar pores, and examine the similarities and the differences between these simple systems and water in more complex pores.
C1 [Dellago, Christoph] Univ Vienna, Fac Phys, A-1090 Vienna, Austria.
[Dellago, Christoph] Univ Vienna, Ctr Computat Mat Sci, A-1090 Vienna, Austria.
[Koefinger, Juergen; Hummer, Gerhard] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Dellago, C (reprint author), Univ Vienna, Fac Phys, Boltzmanngasse 5, A-1090 Vienna, Austria.
RI Hummer, Gerhard/A-2546-2013
OI Hummer, Gerhard/0000-0001-7768-746X
FU National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health; Austrian Science Foundation (FWF) [SFB
ViCoM (F 41)]
FX J.K. and G.H. were supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health. C.D. gratefully acknowledges financial
support by the Austrian Science Foundation (FWF) within the SFB ViCoM (F
41).
NR 160
TC 43
Z9 44
U1 7
U2 71
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 1463-9076
EI 1463-9084
J9 PHYS CHEM CHEM PHYS
JI Phys. Chem. Chem. Phys.
PY 2011
VL 13
IS 34
BP 15403
EP 15417
DI 10.1039/c1cp21086f
PG 15
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 807LT
UT WOS:000293900400003
PM 21779552
ER
PT J
AU Best, RB
Hummer, G
AF Best, Robert B.
Hummer, Gerhard
TI Diffusion models of protein folding
SO PHYSICAL CHEMISTRY CHEMICAL PHYSICS
LA English
DT Article
ID BETA-HAIRPIN FORMATION; SINGLE-MOLECULE FRET; FREE-ENERGY; SPEED LIMIT;
NONNATIVE INTERACTIONS; DEPENDENT DIFFUSION; REACTION COORDINATE;
TRANSITION-STATES; REACTION DYNAMICS; EXPLICIT-SOLVENT
AB In theory and in the analysis of experiments, protein folding is often described as diffusion along a single coordinate. We explore here the application of a one-dimensional diffusion model to interpret simulations of protein folding, where the parameters of a model that "best" describes the simulation trajectories are determined using a Bayesian analysis. We discuss the requirements for such a model to be a good approximation to the global dynamics, and several methods for testing its accuracy. For example, one test considers the effect of an added bias potential on the fitted free energies and diffusion coefficients. Such a bias may also be used to extend our approach to determining parameters for the model to systems that would not normally explore the full coordinate range on accessible time scales. Alternatively, the propagators predicted from the model at different "lag" times may be compared with observations from simulation. We then present some applications of the model to protein folding, including Kramers-like turnover in folding rates of coarse-grained models, the effect of non-native interactions on folding, and the effect of the chosen coordinate on the observed position-dependence of the diffusion coefficients. Lastly, we consider how our results are useful for the interpretation of experiments, and how this type of Bayesian analysis may eventually be applied directly to analyse experimental data.
C1 [Best, Robert B.] Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England.
[Hummer, Gerhard] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Best, RB (reprint author), Univ Cambridge, Dept Chem, Lensfield Rd, Cambridge CB2 1EW, England.
EM rbb24@cam.ac.uk; gerhard.hummer@nih.gov
RI Hummer, Gerhard/A-2546-2013; Best, Robert/H-7588-2016
OI Hummer, Gerhard/0000-0001-7768-746X; Best, Robert/0000-0002-7893-3543
FU Royal Society; National Institute of Diabetes and Digestive and Kidney
Diseases, National Institutes of Health
FX R.B. is supported by a Royal Society University Research Fellowship.
G.H. is supported by the Intramural Research Program of the National
Institute of Diabetes and Digestive and Kidney Diseases, National
Institutes of Health.
NR 64
TC 29
Z9 29
U1 3
U2 38
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 1463-9076
J9 PHYS CHEM CHEM PHYS
JI Phys. Chem. Chem. Phys.
PY 2011
VL 13
IS 38
BP 16902
EP 16911
DI 10.1039/c1cp21541h
PG 10
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 823NC
UT WOS:000295128000002
PM 21842082
ER
PT J
AU McGlinchey, RP
Yap, TL
Lee, JC
AF McGlinchey, Ryan P.
Thai Leong Yap
Lee, Jennifer C.
TI The yin and yang of amyloid: insights from alpha-synuclein and repeat
domain of Pmel17
SO PHYSICAL CHEMISTRY CHEMICAL PHYSICS
LA English
DT Article
ID MATRIX PROTEIN PMEL17/GP100; PINK-EYED DILUTION; SOLID-STATE NMR;
PARKINSONS-DISEASE; LEWY-BODY; IN-VITRO; TRYPTOPHAN FLUORESCENCE;
ELECTRON-TRANSFER; CONTACT DYNAMICS; FIBRIL STRUCTURE
AB Amyloid has been traditionally viewed in the context of disease. However, the emerging concept of 'functional amyloid' has taken a new direction into how we view amyloid. Recent studies have identified amyloid fibrils ranging from bacteria to humans that have a beneficial role, instead of being associated with a misfolded state that has been implicated in diseases such as Alzheimer's, Parkinson's and prion diseases. Here, we review our work on two human amyloidogenic polypeptides, one associated with Parkinson's disease, alpha-synuclein (alpha-syn), and the other important for melanin synthesis, the repeat domain (RPT) from Pmel17. Particularly, we focused our attention on spectroscopic studies of protein conformation and dynamics and their impact on alpha-syn amyloid formation and for RPT, we discussed the strict pH dependence of amyloid formation and its role in melanin biosynthesis.
C1 [McGlinchey, Ryan P.; Thai Leong Yap; 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 Institutes of Health, National Heart, Lung, and Blood Institute
FX This work was supported by the Intramural Research Program at the
National Institutes of Health, National Heart, Lung, and Blood
Institute. We thank Rob Tycko in providing the A beta amyloid structure
and Candace Pfefferkorn for discussion.
NR 103
TC 12
Z9 12
U1 1
U2 10
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 1463-9076
J9 PHYS CHEM CHEM PHYS
JI Phys. Chem. Chem. Phys.
PY 2011
VL 13
IS 45
BP 20066
EP 20075
DI 10.1039/c1cp21376h
PG 10
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 846BF
UT WOS:000296871500003
PM 21993592
ER
PT J
AU Cintas, HL
Parks, R
Don, S
Gerber, L
AF Cintas, Holly Lea
Parks, Rebecca
Don, Sarah
Gerber, Lynn
TI Brief Assessment of Motor Function: Content Validity and Reliability of
the Upper Extremity Gross Motor Scale
SO PHYSICAL & OCCUPATIONAL THERAPY IN PEDIATRICS
LA English
DT Article
DE Evidence-based practice; knowledge translation; mobility; motor
development
ID SUPINE POSITION; ERECT STANCE; MOVEMENT; INFANT; RISE
AB Content validity and reliability of the Brief Assessment of Motor Function (BAMF) Upper Extremity Gross Motor Scale (UEGMS) were evaluated in this prospective, descriptive study. The UEGMS is one of five BAMF ordinal scales designed for quick documentation of gross, fine, and oral motor skill levels. Designed to be independent of age and diagnosis, it is intended for use for infants through young adults. An expert panel of 17 physical therapists and 13 occupational therapists refined the content by responding to a standard questionnaire comprised of questions, which asked whether each item should be included, is clearly worded, should be reordered higher or lower, is functionally relevant, and is easily discriminated. Ratings of content validity exceeded the criterion except for two items, which may represent different perspectives of physical and occupational therapists. The UEGMS was modified using the quantitative and qualitative feedback from the questionnaires. For reliability, five raters scored videotaped motor performances of 10 children. Coefficients for inter-rater (0.94) and intra-rater (0.95) reliability were high. The results provide evidence of content validity and reliability of the UEGMS for the assessment of UEGM skill.
C1 [Cintas, Holly Lea] NIH, Phys Therapy Sect, Dept Rehabil Med, Mark O Hatfield Clin Res Ctr, Bethesda, MD 20892 USA.
[Don, Sarah] Envoy Rehabil Ctr, Occupat Therapy Dept, Pikesville, MD USA.
[Gerber, Lynn] George Mason Univ, Ctr Chron Illness & Disabil, Fairfax, VA 22030 USA.
RP Cintas, HL (reprint author), NIH, Phys Therapy Sect, Dept Rehabil Med, Mark O Hatfield Clin Res Ctr, Bldg 10 CRC,Room 1-1469 NE, Bethesda, MD 20892 USA.
EM holly_cintas@nih.gov
FU NIH
FX We would like to acknowledge the valuable advice and direction provided
by Gloria Furst, OTR/L, MPH, Consultant, Rehabilitation Medicine
Department, NIH. We also would like to thank the parents and their
children who participated in the reliability study, and the physical
therapists, occupational therapists, and the physical and occupational
therapy students who shared their time and expertise to complete the
content validity and reliability studies. The NIH Intramural Research
Program funded this study.
NR 24
TC 1
Z9 1
U1 0
U2 1
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0194-2638
J9 PHYS OCCUP THER PEDI
JI Phys. Occup. Ther. Pediatr.
PY 2011
VL 31
IS 4
BP 440
EP 450
DI 10.3109/01942638.2011.572148
PG 11
WC Pediatrics; Rehabilitation
SC Pediatrics; Rehabilitation
GA 833NT
UT WOS:000295892900008
PM 21599568
ER
PT J
AU Andjus, PR
Stojilkovic, SS
Cvijic, G
AF Andjus, P. R.
Stojilkovic, S. S.
Cvijic, G.
TI Ivan Djaja (Jean Giaja) and the Belgrade School of Physiology
SO PHYSIOLOGICAL RESEARCH
LA English
DT Article
DE History of physiology; Sorbonne; University of Belgrade; Bioenergetics;
Thermoregulation; Neuroendocrine regulation
ID SQUIRREL CITELLUS-CITELLUS; DEVELOPMENTAL PATTERN; MALE-RAT; PROFONDE
HYPOTHERMIE; BODY TEMPERATURES; LH LEVELS; ANDROGEN; REANIMATION
AB The founder of physiology studies in the Balkans and the pioneer of research on hypothermia, Ivan Djaja (Jean Giaja) was born 1884 in L'Havre. Giaja gained his PhD at the Sorbonne in 1909. In 1910 he established the first Chair of Physiology in the Balkans and organized the first Serbian Institute for Physiology at the School of Philosophy of the University of Belgrade. He led this Institute for more than 40 subsequent years. His most notable papers were in the field of thermoregulation and bioenergetics. Djaja became member of the Serbian and Croatian academies of science and doctor honoris causa of Sorbonne. In 1952 for the seminal work on the behavior of deep cooled warm blooded animals he became associate member of the National Medical Academy in Paris. In 1955 the French Academy of Sciences elected him as associate member in place of deceased Sir Alexander Fleming. Djaja died in 1957 during a congress held in his honor. He left more than 200 scientific and other papers and the golden DaVincian credo "Nulla dies sine experimento". His legacy was continued by several generations of researchers, the most prominent among them being Stefan Gelineo, Radoslav Andjus and Vojislav Petrovic.
C1 [Andjus, P. R.; Cvijic, G.] Univ Belgrade, Inst Physiol & Biochem, Fac Biol, Belgrade 11000, Serbia.
[Stojilkovic, S. S.] NICHHD, Sect Cellular Signaling, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
RP Andjus, PR (reprint author), Univ Belgrade, Inst Physiol & Biochem, Fac Biol, Belgrade 11000, Serbia.
EM pandjus@bio.bg.ac.rs
FU Intramural NIH HHS [Z01 HD000195-15]
NR 40
TC 1
Z9 1
U1 0
U2 2
PU ACAD SCIENCES CZECH REPUBLIC, INST PHYSIOLOGY
PI PRAGUE 4
PA VIDENSKA 1083, PRAGUE 4 142 20, CZECH REPUBLIC
SN 0862-8408
J9 PHYSIOL RES
JI Physiol. Res.
PY 2011
VL 60
SU 1
BP S1
EP S13
PG 13
WC Physiology
SC Physiology
GA 838ZT
UT WOS:000296334200001
PM 21777022
ER
PT J
AU Mansky, PJ
Wallerstedt, DB
Sannes, T
Stagl, J
Johnson, LL
Blackman, MR
Grem, JL
Swain, SM
Schlodder, D
Monahan, BP
AF Mansky, P. J.
Wallerstedt, D. B.
Sannes, T.
Stagl, J.
Johnson, L. L.
Blackman, M. R.
Grem, J. L.
Swain, S. M.
Schlodder, D.
Monahan, B. P.
TI NCCAM/NCI phase 1 study of mistletoe extract and Gemcitabine in patients
with advanced solid tumors
SO PHYTOMEDICINE
LA English
DT Meeting Abstract
DE Mistletoe; Safety and toxicity; Phase I trial
C1 [Mansky, P. J.] Bellin Hlth, Green Bay, WI USA.
[Mansky, P. J.; Wallerstedt, D. B.; Sannes, T.; Stagl, J.; Johnson, L. L.] Natl Ctr Complementary & Alternat Med, NIH, Bethesda, MD USA.
[Blackman, M. R.] Vet Affairs Med Ctr, Res Serv, Washington, DC 20422 USA.
[Grem, J. L.] Univ Nebraska Medcl Ctr, Omaha, NE USA.
[Swain, S. M.] Washington Hosp Ctr, Washington, DC 20010 USA.
[Schlodder, D.] Helixor Heilmittel GmbH & Co KG, Rosenfeld, Germany.
[Monahan, B. P.] Congress US, Washington, DC USA.
EM manpaj@bellin.org
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER GMBH, URBAN & FISCHER VERLAG
PI JENA
PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY
SN 0944-7113
J9 PHYTOMEDICINE
JI Phytomedicine
PY 2011
VL 18
SU 8
BP S12
EP S12
DI 10.1016/j.phymed.2011.09.029
PG 1
WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary
Medicine; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary
Medicine
GA 850ID
UT WOS:000297187400023
ER
PT J
AU White, JG
Gunay-Aygun, M
AF White, James G.
Gunay-Aygun, Meral
TI The York Platelet Syndrome: A third case
SO PLATELETS
LA English
DT Article
ID ELECTRON-DENSE CHAINS; INHERITED THROMBOCYTOPENIC DISORDER;
MEGAKARYOCYTES; CLUSTERS; GRANULES; BODIES
AB Our present study has described a third patient with the York Platelet Syndrome (YPS). The condition consists of a mitochondrial myopathy associated with unique platelet pathology. Their mitochondrial myopathy has not been completely delineated and will be the subject of further study. Platelet pathology in the new patient is essentially identical to that described in the first two patients. Thin sections of her thrombocytes reveal a normal complement of alpha alpha and delta delta granules (dense bodies) in some, a decreased number in others and complete absence in a few. The unique pathological feature is the presence of giant organelles, including an intensely electron dense, huge body, the opaque organelle (OO) and a multilayered large body, the target organelle. In addition platelets from the new patient contain large masses and coils of smooth endoplasmic reticulum present infrequently in platelets of the first two patients. The giant opaque and target organelles appear to develop in rough and smooth endoplasmic reticulum of the parent megakaryocyte and mature in the dense tubular system of circulating platelets. The relationship of the unique platelet pathology and mitochondrial myopathy has not been defined.= 3 g/dL and/or >= 10% clonal bone marrow plasma cells, in the absence of end-organ damage. Based on clinical observations, the natural history of SMM varies greatly, from stable, monoclonal gammopathy of undetermined significance (MGUS)-like disease to highly progressive disease. Using conventional clinical markers, SMM patients can be stratified into clinical risk groups. However, due to considerable molecular heterogeneity, we currently lack reliable markers to predict prognosis for individual SMM patients. Based on the International Myeloma Working Group 2010 guidelines, patients diagnosed with MGUS and SMM should not be treated outside of clinical trials. Overall, treatment trials for MGUS patients are complicated, as these individuals are relatively healthy and the majority has a low life-time risk of progression, especially when other causes of death are taken into account. In contrast to MGUS, early treatment strategies for SMM are particularly attractive, as the rate of progression to multiple myeloma is substantially higher. Until recently, potent drugs with reasonable toxicity profiles have not been available for the development of early multiple myeloma treatment strategies. This review discusses how the integration of novel biological markers and clinical monitoring of SMM could facilitate the development of early treatment strategies for high-risk SMM patients in the future. Semin Hematol 48:66-72. 2011 Published by Elsevier Inc.
C1 [Landgren, Ola] NCI, NIH, Ctr Canc Res, Med Oncol Branch, Bethesda, MD 20892 USA.
[Rajkumar, S. Vincent] Mayo Clin, Div Hematol, Rochester, MN USA.
RP Landgren, O (reprint author), NCI, NIH, Ctr Canc Res, Med Oncol Branch, 9000 Rockville Pike,Bldg 10,Room 13N240, Bethesda, MD 20892 USA.
EM landgreo@mail.nih.gov
OI Rajkumar, S. Vincent/0000-0002-5862-1833
FU National Cancer Institute of the National Institutes of Health; National
Cancer Institute [CA 62242, CA 107-476-03]; Division of Hematology at
the Mayo Clinic, Rochester, MN; Division of Biostatistics at the Mayo
Clinic, Rochester, MN; Division of Clinical Biochemistry at the Mayo
Clinic, Rochester, MN; Division of Immunology at the Mayo Clinic,
Rochester, MN
FX This work was supported by the Intramural Research Program of the
National Cancer Institute of the National Institutes of Health; grants
no. CA 62242 and CA 107-476-03 from the National Cancer Institute; and
the facilities and resources of the Divisions of Hematology,
Biostatistics, Clinical Biochemistry and Immunology, and Epidemiology at
the Mayo Clinic, Rochester, MN.
NR 43
TC 4
Z9 4
U1 0
U2 1
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0037-1963
EI 1532-8686
J9 SEMIN HEMATOL
JI Semin. Hematol.
PD JAN
PY 2011
VL 48
IS 1
BP 66
EP 72
DI 10.1053/j.seminhematol.2010.11.009
PG 7
WC Hematology
SC Hematology
GA 709AA
UT WOS:000286406100009
PM 21232660
ER
PT J
AU Bouchelouche, K
Tagawa, ST
Goldsmith, SJ
Turkbey, B
Capala, J
Choyke, P
AF Bouchelouche, Kirsten
Tagawa, Scott T.
Goldsmith, Stanley J.
Turkbey, Bans
Capala, Jacek
Choyke, Peter
TI PET/CT Imaging and Radioimmunotherapy of Prostate Cancer
SO SEMINARS IN NUCLEAR MEDICINE
LA English
DT Article; Proceedings Paper
CT 14th International Symposium on Radionuclides in Nephrourology
CY MAY 11-14, 2010
CL Mikulov, CZECH REPUBLIC
ID POSITRON-EMISSION-TOMOGRAPHY; TOSITUMOMAB/IODINE I-131 TOSITUMOMAB;
COMBINED-MODALITY RADIOIMMUNOTHERAPY; MITOXANTRONE PLUS PREDNISONE;
MONOCLONAL-ANTIBODY J591; LYMPH-NODE METASTASES; NON-HODGKIN-LYMPHOMA;
GROUP PROTOCOL S9911; PHASE-I TRIAL; RADICAL PROSTATECTOMY
AB Prostate cancer is a common cancer in men and continues to be a major health problem. Imaging plays an important role in the clinical management of patients with prostate cancer. An important goal for prostate cancer imaging is more accurate disease characterization through the synthesis of anatomic, functional, and molecular imaging information. Positron emission tomography (PET)/computed tomography (CT) in oncology is emerging as an important imaging tool. The most common radiotracer for PET/CT in oncology, F-18-fluorodeoxyglucose (FDG), is not very useful in the imaging of prostate cancer. However, in recent years other PET tracers have improved the accuracy of PET/CT imaging of prostate cancer. Among these, choline labeled with F-18 or C-11, C-11-acetate, and F-18-fluoride has demonstrated promising results, and other new radiopharmaceuticals are under development and evaluation in preclinical and clinical studies. Large prospective clinical PET/CT trials are needed to establish the role of PET/CT in prostate cancer patients. Because there are only limited available therapeutic options for patients with advanced metastatic prostate cancer, there is an urgent need for the development of more effective treatment modalities that could improve outcome. Prostate cancer represents an attractive target for radioimmunotherapy (RIT) for several reasons, including pattern of metastatic spread (lymph nodes and bone marrow, sites with good access to circulating antibodies) and small volume disease (ideal for antigen access and antibody delivery). Furthermore, prostate cancer is also radiation sensitive. Prostate-specific membrane antigen is expressed by virtually all prostate cancers, and represents an attractive target for RIT. Antiprostate-specific membrane antigen RIT demonstrates antitumor activity and is well tolerated. Clinical trials are underway to further improve upon treatment efficacy and patient selection. This review focuses on the recent advances of clinical PET/CT imaging and RIT of prostate cancer. Semin Nucl Med 41:29-44 (C) 2011 Elsevier Inc. All rights reserved.
C1 [Bouchelouche, Kirsten] Univ Copenhagen, Rigshosp, PET 3982, PET & Cyclotron Unit, DK-2100 Copenhagen, Denmark.
[Tagawa, Scott T.] Weill Cornell Med Coll, Div Hematol & Med Oncol, New York, NY USA.
[Goldsmith, Stanley J.] New York Presbyterian Hosp, Weill Cornell Med Ctr, Dept Radiol, Div Nucl Med & Mol Imaging, New York, NY USA.
[Turkbey, Bans; Choyke, Peter] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Capala, Jacek] NCI, Mol Targeting Sect, Radiat Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
RP Bouchelouche, K (reprint author), Univ Copenhagen, Rigshosp, PET 3982, PET & Cyclotron Unit, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
EM bouchelouche@mail.tele.dk
FU Intramural NIH HHS [ZIA BC010727-04]
NR 159
TC 38
Z9 41
U1 1
U2 10
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0001-2998
EI 1558-4623
J9 SEMIN NUCL MED
JI Semin. Nucl. Med.
PD JAN
PY 2011
VL 41
IS 1
BP 29
EP 44
DI 10.1053/j.semnuclmed.2010.08.005
PG 16
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 694GT
UT WOS:000285283700005
PM 21111858
ER
PT J
AU Raghuveer, K
Senthilkumaran, B
Sudhakumari, CC
Sridevi, P
Rajakumar, A
Singh, R
Murugananthkumar, R
Majumdar, KC
AF Raghuveer, K.
Senthilkumaran, B.
Sudhakumari, C. C.
Sridevi, P.
Rajakumar, A.
Singh, R.
Murugananthkumar, R.
Majumdar, K. C.
TI Dimorphic Expression of Various Transcription Factor and Steroidogenic
Enzyme Genes during Gonadal Ontogeny in the Air-Breathing Catfish,
Clarias gariepinus
SO SEXUAL DEVELOPMENT
LA English
DT Article
DE Catfish; Dimorphic expression; Gonadal development; Ovary; Sex
differentiation; Teleosts; Testis
ID TILAPIA OREOCHROMIS-NILOTICUS; SEX-DIFFERENTIATION; TELEOST FISH; NILE
TILAPIA; DMRT1 EXPRESSION; ORYZIAS-LATIPES; MEDAKA; SOX9; REVERSAL;
DEHYDROGENASE
AB In the present study the expression of 13 genes known to be involved in sex differentiation and steroidogenesis in catfish was analyzed during gonadal ontogeny by quantitative real-time RT-PCR. Dmrt1 and sox9a showed exclusive expression in male gonads while ovarian aromatase (cyp19a1) and foxl2 were abundant in differentiating female gonads. Most of the genes related to steroidogenesis were expressed only after gonadal differentiation. However, genes coding for 3 beta-hydroxysteroid dehydrogenase (3 beta-hsd), 17 alpha-hydroxylase/C17-20 lyase type 1 (cyp17) and steroidogenic acute regulatory protein (star) were barely detectable during gonadal differentiation. Ovarian aromatase, cyp19a1, which is responsible for estradiol-17 beta biosynthesis in females, was expressed very early in the undifferentiated gonads of catfish, around 30-40 days post hatch (dph). The steroidogenic enzyme, 11 beta-hydroxylase (cyp11b1) required for the production of 11-ketotestosterone (11-KT) was expressed only after differentiation of testis. These results suggest that estradiol-17 beta has a critical role in ovarian differentiation, while the role of 11-KT in testicular differentiation is doubtful. In conclusion, dimorphic expression of dmrt1 and sox9a in gonads during early development is required for testicular differentiation, and sex-specific expression of cyp19a1 and foxl2 in females plays a critical role in ovarian development. Our study reveals that the critical period of gonadal differentiation in catfish starts around 30-40 dph when sex-specific genes showed differential expression. Copyright (C) 2011 S. Karger AG, Basel
C1 [Raghuveer, K.; Senthilkumaran, B.; Sudhakumari, C. C.; Sridevi, P.; Rajakumar, A.; Singh, R.; Murugananthkumar, R.] Univ Hyderabad, Dept Anim Sci, Sch Life Sci, Ctr Adv Studies, Hyderabad 500046, Andhra Pradesh, India.
[Majumdar, K. C.] Ctr Cellular & Mol Biol, Hyderabad 500007, Andhra Pradesh, India.
[Raghuveer, K.] NICHD, NIH, Bethesda, MD USA.
RP Senthilkumaran, B (reprint author), Univ Hyderabad, Dept Anim Sci, Sch Life Sci, Ctr Adv Studies, PO Cent Univ, Hyderabad 500046, Andhra Pradesh, India.
EM bsksl@uohyd.ernet.in
RI Perez , Claudio Alejandro/F-8310-2010
OI Perez , Claudio Alejandro/0000-0001-9688-184X
FU University Grants Commission [34-412/2008]; University of Hyderabad
(UH), India; Council of Scientific and Industrial Research/University
Grant Commission; DBT-CREBB, India
FX A Grant-in-Aid from the University Grants Commission (F. No.
34-412/2008) awarded to B. S. and a DST-PURSE grant from the University
of Hyderabad (UH), India supported this work. K. R., P. S., R. S. and R.
M. thank the Council of Scientific and Industrial Research/University
Grant Commission for junior/senior research fellowship. We thank our
Vice-Chancellor, Prof. Seyed E. Hasnain, and the Dean, Prof. M.
Ramanadham, for allowing us to use the Genomics and Microarray facility
of the School of Life Sciences, UH, partially sponsored by DBT-CREBB,
India. All authors thank Prof. Yoshitaka Nagahama from the National
Institute of Basic Biology, Okazaki, Japan for his generous gift of
Cyp19a1 antiserum for our research.
NR 43
TC 34
Z9 36
U1 1
U2 8
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 1661-5425
J9 SEX DEV
JI Sex. Dev.
PY 2011
VL 5
IS 4
BP 213
EP 223
DI 10.1159/000328823
PG 11
WC Developmental Biology
SC Developmental Biology
GA 800BO
UT WOS:000293332400006
PM 21720151
ER
PT J
AU Falade-Nwulia, O
Thio, CL
AF Falade-Nwulia, Oluwaseun
Thio, Chloe L.
TI Liver disease, HIV and aging
SO SEXUAL HEALTH
LA English
DT Article
DE cirrhosis; hepatitis; highly active antiretroviral therapy
ID HEPATITIS-C-VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; ALPHA-2A PLUS
RIBAVIRIN; ACTIVE ANTIRETROVIRAL THERAPY; INFECTED PATIENTS; B-VIRUS;
HEPATOCELLULAR-CARCINOMA; UNITED-STATES; ELDERLY-PATIENTS;
NATURAL-HISTORY
AB The life expectancy of HIV-infected patients has increased due to the efficacy of highly active antiretroviral therapy (HAART) in controlling HIV replication; thus, the population living with HIV infection is steadily aging. Liver-related morbidity and mortality has emerged as a leading problem in HIV-infected patients. Since aging, HIV infection and HAART all affect the liver, understanding the impact of the combination of these factors on liver disease is crucial for optimisation of care in the aging HIV-infected population. This review will focus on the current understanding of liver disease in older (>50 years old) HIV-negative individuals and in HIV-infected individuals. Areas for future research in the area of HIV, liver disease and aging will also be discussed.
C1 [Falade-Nwulia, Oluwaseun; Thio, Chloe L.] Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21231 USA.
[Falade-Nwulia, Oluwaseun] NIH, Crit Care Med Dept, Bethesda, MD 20892 USA.
RP Falade-Nwulia, O (reprint author), Johns Hopkins Univ, Sch Med, Div Infect Dis, 855 N Wolfe St,Suite 520, Baltimore, MD 21231 USA.
EM faladeoo@cc.nih.gov
FU NIH [AI060449, AI017820]
FX CLT is supported by NIH grants AI060449 and AI017820.
NR 89
TC 5
Z9 5
U1 0
U2 0
PU CSIRO PUBLISHING
PI COLLINGWOOD
PA 150 OXFORD ST, PO BOX 1139, COLLINGWOOD, VICTORIA 3066, AUSTRALIA
SN 1448-5028
J9 SEX HEALTH
JI Sex Health
PY 2011
VL 8
IS 4
SI SI
BP 512
EP 520
DI 10.1071/SH10163
PG 9
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 844UM
UT WOS:000296774000010
PM 22127037
ER
PT B
AU Farci, P
AF Farci, Patrizia
BE Dooley, JS
Lok, AF
Burroughs, AK
Heathcote, EJ
TI Hepatitis D
SO SHERLOCK'S DISEASES OF THE LIVER AND BILIARY SYSTEM, 12TH EDITION
LA English
DT Article; Book Chapter
ID CHRONIC DELTA-HEPATITIS; B SURFACE-ANTIGEN; INTERFERON-ALPHA TREATMENT;
IMMUNODEFICIENCY-VIRUS-INFECTION; NORTHERN SOUTH-AMERICA; C-VIRUS;
LIVER-DISEASE; PEGYLATED INTERFERON-ALPHA-2B; MAJOR CLADES; GENOTYPE-II
C1 NIAID, Hepat Pathogenesis Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Farci, P (reprint author), NIAID, Hepat Pathogenesis Sect, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
NR 76
TC 1
Z9 1
U1 0
U2 0
PU BLACKWELL SCIENCE PUBL
PI OXFORD
PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND
BN 978-1-4443-4126-3; 978-1-4051-3489-7
PY 2011
BP 393
EP 405
D2 10.1002/9781444341294
PG 13
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA BB8MA
UT WOS:000346850500021
ER
PT B
AU Seeff, LB
Fontana, RJ
AF Seeff, Leonard B.
Fontana, Robert J.
BE Dooley, JS
Lok, AF
Burroughs, AK
Heathcote, EJ
TI Drug-Induced Liver Injury
SO SHERLOCK'S DISEASES OF THE LIVER AND BILIARY SYSTEM, 12TH EDITION
LA English
DT Article; Book Chapter
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; INDUCED HEPATIC-INJURY; CHRONIC
ACTIVE HEPATITIS; ENDOPLASMIC-RETICULUM AUTOANTIBODIES;
DIHYDRALAZINE-INDUCED HEPATITIS; DICLOFENAC-INDUCED HEPATITIS; CAUSALITY
ASSESSMENT METHOD; OF-THE-LITERATURE; SALT EXPORT PUMP; INDUCED
HEPATOTOXICITY
C1 [Seeff, Leonard B.] NIDDK, NIH, Bethesda, MD 20892 USA.
[Fontana, Robert J.] Univ Michigan, Sch Med, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI USA.
NR 285
TC 0
Z9 0
U1 0
U2 1
PU BLACKWELL SCIENCE PUBL
PI OXFORD
PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND
BN 978-1-4443-4126-3; 978-1-4051-3489-7
PY 2011
BP 478
EP 506
D2 10.1002/9781444341294
PG 29
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA BB8MA
UT WOS:000346850500026
ER
PT B
AU Chen, Z
AF Chen, Zhong
BE Glick, AB
VanWaes, C
TI Aberrant Activation of HGF/c-MET Signaling and Targeted Therapy in
Squamous Cancer
SO SIGNALING PATHWAYS IN SQUAMOUS CANCER
LA English
DT Article; Book Chapter
ID HEPATOCYTE GROWTH-FACTOR; RECEPTOR TYROSINE KINASE; COMPARATIVE GENOMIC
HYBRIDIZATION; PAPILLARY RENAL-CARCINOMAS; TUMOR-STROMAL INTERACTIONS;
CELLS IN-VITRO; FACTOR-KAPPA-B; C-MET; FACTOR/SCATTER FACTOR;
SCATTER-FACTOR
AB Aberrant activation of the c-MET signaling pathway has been identified in multiple carcinomas, including bladder, renal, cervical, colon, breast, ovary, lung, esophagus, gastric, and head and neck cancers The underlying genetic and functional abnormalities include gene amplification of c-MET/hepatocyte growth factor (HGF) gene loci, c-MET mutation, overexpression of c-MET and HGF due to transcriptional dysregulation or promoter polymorphisms, and autocrine or paracrine activation mediated by cytokines and growth factors HGF/c-MET signaling promotes an aggressive malignant phenotype, including increased cell proliferation and survival, epithelial-mesenchymal transition (EMT), invasion, angiogenesis and inflammation, and metastasis HGF and its coregulated proinflammatory and proangiogenic growth factors in serum, as well as c-MET mutation, amplification and phosphorylation in tumor specimens, have been identified as important indicators for patient prognosis and responses to therapies targeting HGF/c MET Targeting HGF/c-MET and related signaling pathways are important strategies in the development of anticancer drugs, and a panel of small molecule inhibitors and biological antagonists have been tested in clinical trials
C1 Natl Inst Deafness & Other Commun Disorders, Head & Neck Surg Branch, NIH, Bethesda, MD 20892 USA.
RP Chen, Z (reprint author), Natl Inst Deafness & Other Commun Disorders, Head & Neck Surg Branch, NIH, 10 Ctr Dr,Bldg 10,5D55, Bethesda, MD 20892 USA.
NR 115
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES
BN 978-1-4419-7202-6
PY 2011
BP 91
EP 111
DI 10.1007/978-1-4419-7203-3_4
D2 10.1007/978-1-4419-7203-3
PG 21
WC Oncology
SC Oncology
GA BSQ66
UT WOS:000285483600004
ER
PT B
AU Cataisson, C
Yuspa, SH
AF Cataisson, Christophe
Yuspa, Stuart H.
BE Glick, AB
VanWaes, C
TI Interacting Signaling Pathways in Mouse Skin Tumor Initiation and
Progression
SO SIGNALING PATHWAYS IN SQUAMOUS CANCER
LA English
DT Article; Book Chapter
ID PROTEIN-KINASE-C; GROWTH-FACTOR RECEPTOR; NF-KAPPA-B; SQUAMOUS-CELL
CARCINOMAS; NECROSIS-FACTOR-ALPHA; TRANSGENIC MICE; ONCOGENIC RAS;
CHEMOKINE EXPRESSION; EPIDERMAL NEOPLASIA; HA-RAS
AB The multistage induction of squamous cell cancer (SCC) on mouse skin as a consequence of chemical exposures has remarkable phenotypic and genotypic homology to human SCC development Genetically altered mouse models have been instrumental in defining the respective contribution of signaling pathways on the development of SCC in vivo Central to the skin carcinogenesis process is the activation of the EGFR Ras-MAPK pathway While hyperactivation of the pathway can often be attributed to activating mutations in ras genes, it appears that for the majority of cases the pathway is activated by alterations in upstream modulators as well as downstream effectors that are integral to the altered phenotype of the initiated keratinocytes This chapter will review data from experimental inductions of cutaneous SCC with a special emphasis on mouse models Particularly, the role of the EGFR-Ras-MAPK pathway, protein kinase C, nuclear factor kappa B and the expression of proinflammatory factors by transformed keratinocyte will be covered in more detail
C1 [Cataisson, Christophe; Yuspa, Stuart H.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA.
RP Yuspa, SH (reprint author), NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA.
NR 96
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES
BN 978-1-4419-7202-6
PY 2011
BP 149
EP 164
DI 10.1007/978-1-4419-7203-3_7
D2 10.1007/978-1-4419-7203-3
PG 16
WC Oncology
SC Oncology
GA BSQ66
UT WOS:000285483600007
ER
PT B
AU Peters, JM
Gonzalez, FJ
AF Peters, Jeffrey M.
Gonzalez, Frank J.
BE Glick, AB
VanWaes, C
TI Regulation of Squamous Cell Carcinoma Carcinogenesis by Peroxisome
Proliferator-Activated Receptors
SO SIGNALING PATHWAYS IN SQUAMOUS CANCER
LA English
DT Article; Book Chapter
ID BETA/DELTA PPAR-BETA/DELTA; SMOOTH-MUSCLE-CELLS; NF-KAPPA-B; LIGAND
ACTIVATION; DELTA AGONIST; MOUSE SKIN; KERATINOCYTE DIFFERENTIATION;
GENE-EXPRESSION; INFLAMMATORY RESPONSE; COLON CARCINOGENESIS
AB Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that respond to endogenous and exogenous signaling molecules and modulate cellular functions PPARs regulate many target genes that in turn influence cell growth, differentiation, and inflammatory signaling These changes can occur through direct transcriptional up-regulation of target genes, through secondary changes subsequent to direct transcriptional up regulation of target genes, and through protein-protein interactions The focus of this chapter is to summarize PPAR-dependent regulation of cellular signaling in squamous epithelium, and how these changes influence cancer
C1 [Peters, Jeffrey M.] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, Dept Vet & Biomed Sci, University Pk, PA 16802 USA.
[Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20892 USA.
RP Peters, JM (reprint author), Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, Dept Vet & Biomed Sci, University Pk, PA 16802 USA.
NR 105
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES
BN 978-1-4419-7202-6
PY 2011
BP 223
EP 240
DI 10.1007/978-1-4419-7203-3_11
D2 10.1007/978-1-4419-7203-3
PG 18
WC Oncology
SC Oncology
GA BSQ66
UT WOS:000285483600011
ER
PT B
AU Amornphimoltham, P
Patel, V
Molinolo, A
Gutkind, JS
AF Amornphimoltham, Panomwat
Patel, Vyomesh
Molinolo, Alfredo
Gutkind, J. Silvio
BE Glick, AB
VanWaes, C
TI Head and Neck Cancer and the PI3K/Akt/mTOR Signaling Network: Novel
Molecular Targeted Therapies
SO SIGNALING PATHWAYS IN SQUAMOUS CANCER
LA English
DT Article; Book Chapter
ID SQUAMOUS-CELL CARCINOMA; RICTOR-MTOR COMPLEX; MAMMALIAN TARGET; ORAL
CARCINOGENESIS; HUMAN-DISEASE; PHASE-II; KINASE-B; RAPAMYCIN; PATHWAY;
PHOSPHORYLATION
AB Head and neck squamous cell carcinoma (HNSCC) represents the sixth most common cancer among men worldwide Despite significant advances in conventional therapies for other prevalent cancer types, the survival rate of HNSCC patients has barely improved over the past 3 decades, emphasizing the urgent need for the development of more effective treatment strategies A better understanding of the mechanisms of tumorigenesis has led to novel molecular targeted options for cancer treatment In this regard, we have observed that the persistent activation of the v-akt murine thymoma viral oncogene homolog 1Akt pathway is a frequent event in HNSCC Akt promotes cell proliferation by coordinating mitogenic signaling with energy and nutrient sensing pathways that control protein synthesis through the mammalian target of rapamycin (mTOR) This kinase, in turn, phosphorylates and activates key regulatory circuitries involved in mRNA translation, cell metabolism, and cell cycle control Indeed, the activation of mTOR was found to be a widespread event in HNSCC, as judged by the detection of phospho-S6 (pS6), one of the most downstream targets of mTOR, in more than 80% of human HNSCCs The promising development of mTOR inhibitors, including rapamycin (sirolimus) and its derivatives known as rapalogs, such as CCI-779 (temsilorimus), RAD001 (everolimus), and AP23573 (deterolimus), as antitumor agents prompted us to investigate the effects of rapamycin in HNSCC Indeed rapamycin treatment rapidly reduced the enhanced level of pS6 in vitro and in xenograft models Furthermore, rapamycin displays a potent antitumor effect in vivo, as it Induces apoptosis in HNSCC xenografts, and promotes the regression of chemically induced SCC lesions in skin and oral cancer models and in newly developed oral-specific, genetically defined mouse cancer models In this chapter, we will describe a series of research efforts aimed at addressing dysregulated molecular mechanisms in HNSCC, focusing on the PI3K-Akt-mTOR signaling axis We will also discuss recent and ongoing studies on the molecular targets of mTOR in HNSCC, and emerging experimental information supporting the effectiveness of mTOR inhibitors for the prevention and treatment of HNSCC
C1 [Amornphimoltham, Panomwat; Patel, Vyomesh; Molinolo, Alfredo; Gutkind, J. Silvio] Natl Inst Craniofacial & Dent Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
RP Gutkind, JS (reprint author), Natl Inst Craniofacial & Dent Res, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr,Bldg 30,Room 212, Bethesda, MD 20892 USA.
NR 80
TC 1
Z9 1
U1 0
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES
BN 978-1-4419-7202-6
PY 2011
BP 407
EP 429
DI 10.1007/978-1-4419-7203-3_19
D2 10.1007/978-1-4419-7203-3
PG 23
WC Oncology
SC Oncology
GA BSQ66
UT WOS:000285483600019
ER
PT S
AU Seol, Y
Neuman, KC
AF Seol, Yeonee
Neuman, Keir C.
BE Mashanov, GI
Batters, C
TI Single-Molecule Measurements of Topoisomerase Activity with Magnetic
Tweezers
SO SINGLE MOLECULE ENZYMOLOGY: METHODS AND PROTOCOLS
SE Methods in Molecular Biology
LA English
DT Article; Book Chapter
DE Magnetic tweezers; Single molecule; DNA topology; DNA topoisomerase
ID DNA TOPOISOMERASES; TOPOLOGY; FORCE; MICROMANIPULATION; LEVEL
AB Magnetic tweezers provide a versatile tool enabling the precise application of force and torque on individual biomolecules. These properties make magnetic tweezers uniquely suited for the study of DNA topology and topoisomerases at the single-molecule level. Single-molecule approaches, which are complementary to ensemble biochemical and structural approaches, have provided remarkable insights into the mechanisms of topoisomerase activity and interactions with DNA. Here, we describe how to make single-molecule measurements of topoisomerase activity with a magnetic tweezers instrument. We provide detailed instructions for preparing and characterizing DNA substrates, flow cells, and supercoilable DNA tethers. We then describe magnetic tweezers measurements of supercoil relaxation by single topoisomerases.
C1 [Seol, Yeonee; Neuman, Keir C.] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA.
RP Seol, Y (reprint author), NHLBI, Lab Mol Biophys, NIH, Bldg 10, Bethesda, MD 20892 USA.
RI Neuman, Keir/F-7400-2011
OI Neuman, Keir/0000-0002-0863-5671
FU Intramural NIH HHS
NR 18
TC 10
Z9 10
U1 2
U2 3
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA
SN 1064-3745
BN 978-1-61779-260-1
J9 METHODS MOL BIOL
JI Methods Mol. Biol.
PY 2011
VL 778
BP 229
EP 241
DI 10.1007/978-1-61779-261-8_15
D2 10.1007/978-1-61779-261-8
PG 13
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA BWO08
UT WOS:000294369000015
PM 21809210
ER
PT B
AU Alevizos, I
Chiorini, JA
Nikolov, NP
AF Alevizos, Ilias
Chiorini, John A.
Nikolov, Nikolay P.
BE Fox, RI
Fox, CM
TI Into the Future: Autonomic Neuropathy, MicroRNAs, and Gene Therapy
SO SJOGREN'S SYNDROME: PRACTICAL GUIDELINES TO DIAGNOSIS AND THERAPY
LA English
DT Article; Book Chapter
DE Autonomic nervous system; Dysautonomia; microRNA; Gene therapy
ID PRIMARY SJOGRENS-SYNDROME; CAENORHABDITIS-ELEGANS; MURINE MODEL; CANCER;
EXPRESSION; RNAS; BIOMARKERS; IDENTIFICATION; PROGNOSIS; DIAGNOSIS
AB Understanding the pathogenesis of Sjogren's syndrome (SS) has proved to be challenging. Both immune-mediated and non-immune-mediated mechanisms have been implicated, which adds to the complexity of the problem. However, recent developments in science and technology have given researchers new opportunities for exploring this fascinating disease. In this chapter we provide a synopsis of the progress in our understanding of the role of the autonomic nervous system in SS pathogenesis, the role of microRNAs as novel tools in advancing research in this field, and gene therapy as potential therapeutic avenue.
C1 [Alevizos, Ilias; Nikolov, Nikolay P.] Natl Inst Dent & Craniofacial Res, Sjogrens Syndrome Clin, Bethesda, MD USA.
[Chiorini, John A.] Natl Inst Dent & Craniofacial Res, Dept Mol Physiol, Bethesda, MD USA.
[Chiorini, John A.] Natl Inst Dent & Craniofacial Res, Therapeut Branch, Bethesda, MD USA.
RP Nikolov, NP (reprint author), Natl Inst Dent & Craniofacial Res, Sjogrens Syndrome Clin, Bethesda, MD USA.
EM alvizosi@nidcr.nih.gov; jchiorin@mail.nih.gov; nikolovn@mail.nih.gov
NR 36
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES
BN 978-1-60327-956-7
PY 2011
BP 483
EP 488
DI 10.1007/978-1-60327-957-4_34
D2 10.1007/978-1-60327-957-4
PG 6
WC Rheumatology
SC Rheumatology
GA BZP36
UT WOS:000302322600034
ER
PT J
AU Wu, CW
Liu, P
Wu, Y
Chen, C
Yang, Y
Lin, C
AF Wu, C. W.
Liu, P.
Wu, Y.
Chen, C.
Yang, Y.
Lin, C.
TI DESYNCHRONIZATION OF SENSORIMOTOR AND DEFAULT-MODE NETWORKS DURING FIRST
SLEEP CYCLE
SO SLEEP
LA English
DT Meeting Abstract
CT 25th Anniversary Meeting of the Associated-Professional-Sleep-Societies
(APSS)
CY JUN 11-15, 2011
CL Minneapolis, MN
SP Associated Profess Sleep Soc (APSS)
C1 [Wu, C. W.; Yang, Y.] NIDA, Neuroimaging Res Branch, Baltimore, MD USA.
[Lin, C.] Natl Yang Ming Univ, Inst Neurosci, Taipei 112, Taiwan.
[Chen, C.] Kaohsiung Med Univ, Kaohsiung, Taiwan.
[Wu, Y.] Cheng Hsin Gen Hosp, Med Imaging Dept, Taipei, Taiwan.
[Wu, Y.] Natl Tsing Hua Univ, Inst Nucl Engn & Sci, Hsinchu, Taiwan.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER ACAD SLEEP MEDICINE
PI WESTCHESTER
PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA
SN 0161-8105
J9 SLEEP
JI Sleep
PY 2011
VL 34
SU S
MA 0103
BP A38
EP A39
PG 2
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 886EG
UT WOS:000299834400105
ER
PT S
AU Duyn, J
AF Duyn, Jeff
BE VanSomeren, EJW
VanDerWerf, YD
Roelfsema, PR
Mansvelder, HD
DaSilva, FHL
TI Spontaneous fMRI activity during resting wakefulness and sleep
SO SLOW BRAIN OSCILLATIONS OF SLEEP, RESTING STATE AND VIGILANCE
SE Progress in Brain Research
LA English
DT Review
CT 26th International Summer School of Brain Research
CY JUN 29-JUL 02, 2010
CL Royal Netherlands Acad Arts & Sci (KNAW), Amsterdam, NETHERLANDS
SP UCB Pharma, BIAL Fdn, Jonge Academie, Easycap, Elect Geodes Inc (EGI), Grad Sch Neurosci Amsterdam Rotterdam (ONWAR), Leiden Univ Med Ctr (LUMC), MedCaT, Netherlands Inst Neurosci (NIN), Netherlands Soc Sleep-Wake Res (NSWO), Philips Hlth Care, Philips Consumer Lifestyle, Zorg Onderzoek Nederland-Maatschappij Wetenschappen (ZONMW), VU Univ Amsterdam, Univ Amsterdam, VU Univ Med Ctr
HO Royal Netherlands Acad Arts & Sci (KNAW)
DE sleep; brain function; fmri; spontaneous activity; connectivity;
fluctuations
ID CEREBRAL-BLOOD-FLOW; INTRINSIC FUNCTIONAL CONNECTIVITY;
POSITRON-EMISSION-TOMOGRAPHY; FREQUENCY BOLD FLUCTUATIONS; SPONTANEOUS
BRAIN ACTIVITY; HUMAN VISUAL-CORTEX; SLOW OSCILLATIONS; STATE NETWORKS;
DEFAULT MODE; ALPHA-RHYTHM
AB Functional magnetic resonance imaging (fMRI) studies performed during both waking rest and sleep show that the brain is continually active in distinct patterns that appear to reflect its underlying functional connectivity. In this review, potential sources that contribute to spontaneous fMRI activity will be discussed.
C1 NINDS, Sect Adv MRI, LFMI, NIH, Bethesda, MD 20892 USA.
RP Duyn, J (reprint author), NINDS, Sect Adv MRI, LFMI, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM jhd@helix.nih.gov
FU Intramural NIH HHS [Z01 NS002990-09]
NR 108
TC 7
Z9 7
U1 1
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0079-6123
BN 978-0-44-453838-3
J9 PROG BRAIN RES
JI Prog. Brain Res.
PY 2011
VL 193
BP 295
EP 305
DI 10.1016/B978-0-444-53839-0.00019-3
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA BDA93
UT WOS:000312400500020
PM 21854970
ER
PT J
AU Strenziok, M
Krueger, F
Heinecke, A
Lenroot, RK
Knutson, KM
van der Meer, E
Grafman, J
AF Strenziok, Maren
Krueger, Frank
Heinecke, Armin
Lenroot, Rhoshel K.
Knutson, Kristine M.
van der Meer, Elke
Grafman, Jordan
TI Developmental effects of aggressive behavior in male adolescents
assessed with structural and functional brain imaging
SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE
LA English
DT Article
DE ventromedial prefrontal cortex; frontopolar cortex; fMRI; cortical
thickness; neurodevelopment; trait anger
ID MEDIAL PREFRONTAL CORTEX; POSITRON-EMISSION-TOMOGRAPHY;
PERSONALITY-DISORDER; CORTICAL THICKNESS; MOTOR IMAGERY; SOCIAL BRAIN;
FMRI; ACTIVATION; ANGER; CHILDREN
AB Aggressive behavior is common during adolescence. Although aggression-related functional changes in the ventromedial prefrontal cortex (vmPFC) and frontopolar cortex (FPC) have been reported in adults, the neural correlates of aggressive behavior in adolescents, particularly in the context of structural neurodevelopment, are obscure. We used functional and structural magnetic resonance imaging (MRI) to measure the blood oxygenation level-depended signal and cortical thickness. In a block-designed experiment, 14-17-year old adolescents imagined aggressive and non-aggressive interactions with a peer. We show reduced vmPFC activation associated with imagined aggressive behavior as well as enhanced aggression-related activation and cortical thinning in the FPC with increasing age. Changes in FPC activation were also associated with judgments of the severity of aggressive acts. Reduced vmPFC activation was associated with greater aggression indicating its normal function is to exert inhibitory control over aggressive impulses. Concurrent FPC activation likely reflects foresight of harmful consequences that result from aggressive acts. The correlation of age-dependent activation changes and cortical thinning demonstrates ongoing maturation of the FPC during adolescence towards a refinement of social and cognitive information processing that can potentially facilitate mature social behavior in aggressive contexts.
C1 [Grafman, Jordan] NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA.
[Strenziok, Maren; van der Meer, Elke] Humboldt Univ, Dept Cognit Psychol, Inst Psychol, D-12489 Berlin, Germany.
[Heinecke, Armin] Brain Innovat, NL-6201 BC Maastricht, Netherlands.
[Lenroot, Rhoshel K.] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA.
RP Grafman, J (reprint author), NINDS, Cognit Neurosci Sect, NIH, 10 Ctr Dr,Bldg 10,Room 7D43, Bethesda, MD 20892 USA.
EM grafmanj@ninds.nih.gov
OI Grafman, Jordan H./0000-0001-8645-4457; Knutson,
Kristine/0000-0003-4626-4514
FU National Institutes of Health, National Institute of Neurological
Disorders and Stroke
FX This work was funded by the intramural research program of the National
Institutes of Health, National Institute of Neurological Disorders and
Stroke. We thank Dr Eric Wassermann, Dr Dimitrios Kapogiannis and Dr
Edward Huey for performing the neurological examinations in our
participants.
NR 68
TC 9
Z9 10
U1 4
U2 21
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1749-5016
J9 SOC COGN AFFECT NEUR
JI Soc. Cogn. Affect. Neurosci.
PD JAN
PY 2011
VL 6
IS 1
BP 2
EP 11
DI 10.1093/scan/nsp036
PG 10
WC Neurosciences; Psychology; Psychology, Experimental
SC Neurosciences & Neurology; Psychology
GA 752XT
UT WOS:000289729500002
PM 19770220
ER
PT S
AU Mabry, PL
Hammond, R
Huang, TTK
Ip, EHS
AF Mabry, Patricia L.
Hammond, Ross
Huang, Terry T-K
Ip, Edward Hak-Sing
BE Salerno, J
Yang, SJ
Nau, D
Chai, SK
TI Computational and Statistical Models: A Comparison for Policy Modeling
of Childhood Obesity
SO SOCIAL COMPUTING, BEHAVIORAL-CULTURAL MODELING AND PREDICTION
SE Lecture Notes in Computer Science
LA English
DT Proceedings Paper
CT 4th International Conference on Social Computing, Behavioral-Cultural
Modeling and Prediction
CY MAR 29-31, 2011
CL Coll Pk, MD
C1 [Mabry, Patricia L.] NIH, Off Director, Off Behav & Social Sci Res, Bethesda, MD 20892 USA.
[Hammond, Ross] Ctr Social Dynam & Policy, Brookings Inst, Econ Studies, Washington, DC 20036 USA.
[Huang, Terry T-K] Univ Nebraska, Med Ctr, Coll Publ Hlth, Dept Hlth Promot & Social Behavioral Hlth, Lincoln, NE 68583 USA.
[Ip, Edward Hak-Sing] Wake Forest Univ Hlth Sci, Res & Fac Dev, Div Publ Hlth Sci, Winston Salem, NC 27109 USA.
RP Mabry, PL (reprint author), NIH, Off Director, Off Behav & Social Sci Res, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU SPRINGER-VERLAG BERLIN
PI BERLIN
PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY
SN 0302-9743
BN 978-3-642-19655-3
J9 LECT NOTES COMPUT SC
PY 2011
VL 6589
BP 87
EP +
PG 2
WC Computer Science, Information Systems; Computer Science, Software
Engineering; Computer Science, Theory & Methods
SC Computer Science
GA BXT86
UT WOS:000297039300014
ER
PT J
AU Laugeson, EA
Frankel, F
AF Laugeson, Elizabeth A.
Frankel, Fred
BA Laugeson, EA
Frankel, F
BF Laugeson, EA
Frankel, F
TI Social Skills for Teenagers With Developmental and Autism Spectrum
Disorders THE PEERS TREATMENT MANUAL Introduction
SO SOCIAL SKILLS FOR TEENAGERS WITH DEVELOPMENTAL AND AUTISM SPECTRUM
DISORDERS
LA English
DT Article; Book Chapter
C1 [Frankel, Fred] NIMH, Bethesda, MD USA.
[Frankel, Fred] Ctr Dis Control & Prevent CDC, Atlanta, GA USA.
[Frankel, Fred] NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 4
PU ROUTLEDGE
PI LONDON
PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND
BN 978-0-415-87203-4
PY 2011
BP 3
EP +
PG 15
WC Education, Special; Psychology, Developmental; Pediatrics; Psychiatry;
Psychology; Psychology, Social
SC Education & Educational Research; Psychology; Pediatrics; Psychiatry
GA BUZ15
UT WOS:000290759100001
ER
PT J
AU Laugeson, EA
Frankel, F
AF Laugeson, Elizabeth A.
Frankel, Fred
BA Laugeson, EA
Frankel, F
BF Laugeson, EA
Frankel, F
TI Preparing for Treatment
SO SOCIAL SKILLS FOR TEENAGERS WITH DEVELOPMENTAL AND AUTISM SPECTRUM
DISORDERS
LA English
DT Article; Book Chapter
C1 [Frankel, Fred] NIMH, Bethesda, MD USA.
[Frankel, Fred] Ctr Dis Control & Prevent CDC, Atlanta, GA USA.
[Frankel, Fred] NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ROUTLEDGE
PI LONDON
PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND
BN 978-0-415-87203-4
PY 2011
BP 17
EP 34
PG 18
WC Education, Special; Psychology, Developmental; Pediatrics; Psychiatry;
Psychology; Psychology, Social
SC Education & Educational Research; Psychology; Pediatrics; Psychiatry
GA BUZ15
UT WOS:000290759100002
ER
PT J
AU Laugeson, EA
Frankel, F
AF Laugeson, Elizabeth A.
Frankel, Fred
BA Laugeson, EA
Frankel, F
BF Laugeson, EA
Frankel, F
TI Session 1 Introduction and Conversational Skills I-Trading Information
SO SOCIAL SKILLS FOR TEENAGERS WITH DEVELOPMENTAL AND AUTISM SPECTRUM
DISORDERS
LA English
DT Article; Book Chapter
C1 [Frankel, Fred] NIMH, Bethesda, MD USA.
[Frankel, Fred] Ctr Dis Control & Prevent CDC, Atlanta, GA USA.
[Frankel, Fred] NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ROUTLEDGE
PI LONDON
PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND
BN 978-0-415-87203-4
PY 2011
BP 37
EP 65
PG 29
WC Education, Special; Psychology, Developmental; Pediatrics; Psychiatry;
Psychology; Psychology, Social
SC Education & Educational Research; Psychology; Pediatrics; Psychiatry
GA BUZ15
UT WOS:000290759100003
ER
PT J
AU Laugeson, EA
Frankel, F
AF Laugeson, Elizabeth A.
Frankel, Fred
BA Laugeson, EA
Frankel, F
BF Laugeson, EA
Frankel, F
TI Session 2 Conversational Skills II-Two-Way Conversations
SO SOCIAL SKILLS FOR TEENAGERS WITH DEVELOPMENTAL AND AUTISM SPECTRUM
DISORDERS
LA English
DT Article; Book Chapter
C1 [Frankel, Fred] NIMH, Bethesda, MD USA.
[Frankel, Fred] Ctr Dis Control & Prevent CDC, Atlanta, GA USA.
[Frankel, Fred] NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ROUTLEDGE
PI LONDON
PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND
BN 978-0-415-87203-4
PY 2011
BP 67
EP 93
PG 27
WC Education, Special; Psychology, Developmental; Pediatrics; Psychiatry;
Psychology; Psychology, Social
SC Education & Educational Research; Psychology; Pediatrics; Psychiatry
GA BUZ15
UT WOS:000290759100004
ER
PT J
AU Laugeson, EA
Frankel, F
AF Laugeson, Elizabeth A.
Frankel, Fred
BA Laugeson, EA
Frankel, F
BF Laugeson, EA
Frankel, F
TI Session 3 Conversational Skills III-Electronic Communication
SO SOCIAL SKILLS FOR TEENAGERS WITH DEVELOPMENTAL AND AUTISM SPECTRUM
DISORDERS
LA English
DT Article; Book Chapter
C1 [Frankel, Fred] NIMH, Bethesda, MD USA.
[Frankel, Fred] Ctr Dis Control & Prevent CDC, Atlanta, GA USA.
[Frankel, Fred] NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ROUTLEDGE
PI LONDON
PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND
BN 978-0-415-87203-4
PY 2011
BP 95
EP 123
PG 29
WC Education, Special; Psychology, Developmental; Pediatrics; Psychiatry;
Psychology; Psychology, Social
SC Education & Educational Research; Psychology; Pediatrics; Psychiatry
GA BUZ15
UT WOS:000290759100005
ER
PT J
AU Laugeson, EA
Frankel, F
AF Laugeson, Elizabeth A.
Frankel, Fred
BA Laugeson, EA
Frankel, F
BF Laugeson, EA
Frankel, F
TI Session 4 Choosing Appropriate Friends
SO SOCIAL SKILLS FOR TEENAGERS WITH DEVELOPMENTAL AND AUTISM SPECTRUM
DISORDERS
LA English
DT Article; Book Chapter
C1 [Frankel, Fred] NIMH, Bethesda, MD USA.
[Frankel, Fred] Ctr Dis Control & Prevent CDC, Atlanta, GA USA.
[Frankel, Fred] NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ROUTLEDGE
PI LONDON
PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND
BN 978-0-415-87203-4
PY 2011
BP 125
EP 145
PG 21
WC Education, Special; Psychology, Developmental; Pediatrics; Psychiatry;
Psychology; Psychology, Social
SC Education & Educational Research; Psychology; Pediatrics; Psychiatry
GA BUZ15
UT WOS:000290759100006
ER
PT J
AU Laugeson, EA
Frankel, F
AF Laugeson, Elizabeth A.
Frankel, Fred
BA Laugeson, EA
Frankel, F
BF Laugeson, EA
Frankel, F
TI Session 5 Appropriate Use of Humor
SO SOCIAL SKILLS FOR TEENAGERS WITH DEVELOPMENTAL AND AUTISM SPECTRUM
DISORDERS
LA English
DT Article; Book Chapter
C1 [Frankel, Fred] NIMH, Bethesda, MD USA.
[Frankel, Fred] Ctr Dis Control & Prevent CDC, Atlanta, GA USA.
[Frankel, Fred] NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ROUTLEDGE
PI LONDON
PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND
BN 978-0-415-87203-4
PY 2011
BP 147
EP 170
PG 24
WC Education, Special; Psychology, Developmental; Pediatrics; Psychiatry;
Psychology; Psychology, Social
SC Education & Educational Research; Psychology; Pediatrics; Psychiatry
GA BUZ15
UT WOS:000290759100007
ER
PT J
AU Laugeson, EA
Frankel, F
AF Laugeson, Elizabeth A.
Frankel, Fred
BA Laugeson, EA
Frankel, F
BF Laugeson, EA
Frankel, F
TI Session 6 Peer Entry I-Entering a Conversation
SO SOCIAL SKILLS FOR TEENAGERS WITH DEVELOPMENTAL AND AUTISM SPECTRUM
DISORDERS
LA English
DT Article; Book Chapter
C1 [Frankel, Fred] NIMH, Bethesda, MD USA.
[Frankel, Fred] Ctr Dis Control & Prevent CDC, Atlanta, GA USA.
[Frankel, Fred] NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ROUTLEDGE
PI LONDON
PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND
BN 978-0-415-87203-4
PY 2011
BP 171
EP 197
PG 27
WC Education, Special; Psychology, Developmental; Pediatrics; Psychiatry;
Psychology; Psychology, Social
SC Education & Educational Research; Psychology; Pediatrics; Psychiatry
GA BUZ15
UT WOS:000290759100008
ER
PT J
AU Laugeson, EA
Frankel, F
AF Laugeson, Elizabeth A.
Frankel, Fred
BA Laugeson, EA
Frankel, F
BF Laugeson, EA
Frankel, F
TI Session 7 Peer Entry II-Exiting a Conversation
SO SOCIAL SKILLS FOR TEENAGERS WITH DEVELOPMENTAL AND AUTISM SPECTRUM
DISORDERS
LA English
DT Article; Book Chapter
C1 [Frankel, Fred] NIMH, Bethesda, MD USA.
[Frankel, Fred] Ctr Dis Control & Prevent CDC, Atlanta, GA USA.
[Frankel, Fred] NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ROUTLEDGE
PI LONDON
PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND
BN 978-0-415-87203-4
PY 2011
BP 199
EP 222
PG 24
WC Education, Special; Psychology, Developmental; Pediatrics; Psychiatry;
Psychology; Psychology, Social
SC Education & Educational Research; Psychology; Pediatrics; Psychiatry
GA BUZ15
UT WOS:000290759100009
ER
PT J
AU Laugeson, EA
Frankel, F
AF Laugeson, Elizabeth A.
Frankel, Fred
BA Laugeson, EA
Frankel, F
BF Laugeson, EA
Frankel, F
TI Session 8 Get-Togethers
SO SOCIAL SKILLS FOR TEENAGERS WITH DEVELOPMENTAL AND AUTISM SPECTRUM
DISORDERS
LA English
DT Article; Book Chapter
C1 [Frankel, Fred] NIMH, Bethesda, MD USA.
[Frankel, Fred] Ctr Dis Control & Prevent CDC, Atlanta, GA USA.
[Frankel, Fred] NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ROUTLEDGE
PI LONDON
PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND
BN 978-0-415-87203-4
PY 2011
BP 223
EP 250
PG 28
WC Education, Special; Psychology, Developmental; Pediatrics; Psychiatry;
Psychology; Psychology, Social
SC Education & Educational Research; Psychology; Pediatrics; Psychiatry
GA BUZ15
UT WOS:000290759100010
ER
PT J
AU Laugeson, EA
Frankel, F
AF Laugeson, Elizabeth A.
Frankel, Fred
BA Laugeson, EA
Frankel, F
BF Laugeson, EA
Frankel, F
TI Session 9 Good Sportsmanship
SO SOCIAL SKILLS FOR TEENAGERS WITH DEVELOPMENTAL AND AUTISM SPECTRUM
DISORDERS
LA English
DT Article; Book Chapter
C1 [Frankel, Fred] NIMH, Bethesda, MD USA.
[Frankel, Fred] Ctr Dis Control & Prevent CDC, Atlanta, GA USA.
[Frankel, Fred] NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ROUTLEDGE
PI LONDON
PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND
BN 978-0-415-87203-4
PY 2011
BP 251
EP 266
PG 16
WC Education, Special; Psychology, Developmental; Pediatrics; Psychiatry;
Psychology; Psychology, Social
SC Education & Educational Research; Psychology; Pediatrics; Psychiatry
GA BUZ15
UT WOS:000290759100011
ER
PT J
AU Laugeson, EA
Frankel, F
AF Laugeson, Elizabeth A.
Frankel, Fred
BA Laugeson, EA
Frankel, F
BF Laugeson, EA
Frankel, F
TI Session 10 Rejection I-Teasing and Embarrassing Feedback
SO SOCIAL SKILLS FOR TEENAGERS WITH DEVELOPMENTAL AND AUTISM SPECTRUM
DISORDERS
LA English
DT Article; Book Chapter
C1 [Frankel, Fred] NIMH, Bethesda, MD USA.
[Frankel, Fred] Ctr Dis Control & Prevent CDC, Atlanta, GA USA.
[Frankel, Fred] NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ROUTLEDGE
PI LONDON
PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND
BN 978-0-415-87203-4
PY 2011
BP 267
EP 291
PG 25
WC Education, Special; Psychology, Developmental; Pediatrics; Psychiatry;
Psychology; Psychology, Social
SC Education & Educational Research; Psychology; Pediatrics; Psychiatry
GA BUZ15
UT WOS:000290759100012
ER
PT J
AU Laugeson, EA
Frankel, F
AF Laugeson, Elizabeth A.
Frankel, Fred
BA Laugeson, EA
Frankel, F
BF Laugeson, EA
Frankel, F
TI Session 11 Rejection II-Bullying and Bad Reputations
SO SOCIAL SKILLS FOR TEENAGERS WITH DEVELOPMENTAL AND AUTISM SPECTRUM
DISORDERS
LA English
DT Article; Book Chapter
C1 [Frankel, Fred] NIMH, Bethesda, MD USA.
[Frankel, Fred] Ctr Dis Control & Prevent CDC, Atlanta, GA USA.
[Frankel, Fred] NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ROUTLEDGE
PI LONDON
PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND
BN 978-0-415-87203-4
PY 2011
BP 293
EP 312
PG 20
WC Education, Special; Psychology, Developmental; Pediatrics; Psychiatry;
Psychology; Psychology, Social
SC Education & Educational Research; Psychology; Pediatrics; Psychiatry
GA BUZ15
UT WOS:000290759100013
ER
PT J
AU Laugeson, EA
Frankel, F
AF Laugeson, Elizabeth A.
Frankel, Fred
BA Laugeson, EA
Frankel, F
BF Laugeson, EA
Frankel, F
TI Session 12 Handling Disagreements
SO SOCIAL SKILLS FOR TEENAGERS WITH DEVELOPMENTAL AND AUTISM SPECTRUM
DISORDERS
LA English
DT Article; Book Chapter
C1 [Frankel, Fred] NIMH, Bethesda, MD USA.
[Frankel, Fred] Ctr Dis Control & Prevent CDC, Atlanta, GA USA.
[Frankel, Fred] NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ROUTLEDGE
PI LONDON
PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND
BN 978-0-415-87203-4
PY 2011
BP 313
EP 335
PG 23
WC Education, Special; Psychology, Developmental; Pediatrics; Psychiatry;
Psychology; Psychology, Social
SC Education & Educational Research; Psychology; Pediatrics; Psychiatry
GA BUZ15
UT WOS:000290759100014
ER
PT J
AU Laugeson, EA
Frankel, F
AF Laugeson, Elizabeth A.
Frankel, Fred
BA Laugeson, EA
Frankel, F
BF Laugeson, EA
Frankel, F
TI Session 13 Rumors and Gossip
SO SOCIAL SKILLS FOR TEENAGERS WITH DEVELOPMENTAL AND AUTISM SPECTRUM
DISORDERS
LA English
DT Article; Book Chapter
C1 [Frankel, Fred] NIMH, Bethesda, MD USA.
[Frankel, Fred] Ctr Dis Control & Prevent CDC, Atlanta, GA USA.
[Frankel, Fred] NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ROUTLEDGE
PI LONDON
PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND
BN 978-0-415-87203-4
PY 2011
BP 337
EP 358
PG 22
WC Education, Special; Psychology, Developmental; Pediatrics; Psychiatry;
Psychology; Psychology, Social
SC Education & Educational Research; Psychology; Pediatrics; Psychiatry
GA BUZ15
UT WOS:000290759100015
ER
PT J
AU Laugeson, EA
Frankel, F
AF Laugeson, Elizabeth A.
Frankel, Fred
BA Laugeson, EA
Frankel, F
BF Laugeson, EA
Frankel, F
TI Session 14 Graduation and Termination
SO SOCIAL SKILLS FOR TEENAGERS WITH DEVELOPMENTAL AND AUTISM SPECTRUM
DISORDERS
LA English
DT Article; Book Chapter
C1 [Frankel, Fred] NIMH, Bethesda, MD USA.
[Frankel, Fred] Ctr Dis Control & Prevent CDC, Atlanta, GA USA.
[Frankel, Fred] NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ROUTLEDGE
PI LONDON
PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND
BN 978-0-415-87203-4
PY 2011
BP 359
EP 372
PG 14
WC Education, Special; Psychology, Developmental; Pediatrics; Psychiatry;
Psychology; Psychology, Social
SC Education & Educational Research; Psychology; Pediatrics; Psychiatry
GA BUZ15
UT WOS:000290759100016
ER
PT J
AU Laugeson, EA
Frankel, F
AF Laugeson, Elizabeth A.
Frankel, Fred
BA Laugeson, EA
Frankel, F
BF Laugeson, EA
Frankel, F
TI Case Examples
SO SOCIAL SKILLS FOR TEENAGERS WITH DEVELOPMENTAL AND AUTISM SPECTRUM
DISORDERS
LA English
DT Article; Book Chapter
C1 [Frankel, Fred] NIMH, Bethesda, MD USA.
[Frankel, Fred] Ctr Dis Control & Prevent CDC, Atlanta, GA USA.
[Frankel, Fred] NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ROUTLEDGE
PI LONDON
PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND
BN 978-0-415-87203-4
PY 2011
BP 373
EP 377
PG 5
WC Education, Special; Psychology, Developmental; Pediatrics; Psychiatry;
Psychology; Psychology, Social
SC Education & Educational Research; Psychology; Pediatrics; Psychiatry
GA BUZ15
UT WOS:000290759100017
ER
PT J
AU Arce, FT
Jang, HB
Ramachandran, S
Landon, PB
Nussinov, R
Lal, R
AF Arce, Fernando Teran
Jang, Hyunbum
Ramachandran, Srinivasan
Landon, Preston B.
Nussinov, Ruth
Lal, Ratnesh
TI Polymorphism of amyloid beta peptide in different environments:
implications for membrane insertion and pore formation
SO SOFT MATTER
LA English
DT Article
ID ATOMIC-FORCE MICROSCOPY; ION CHANNELS; ALZHEIMERS-DISEASE;
MOLECULAR-DYNAMICS; CARBON INTERACTION; 3D STRUCTURE; PROTEIN; FIBRILS;
OLIGOMERS; ENERGY
AB Amyloid-beta (A beta) peptides are thought to be involved in neurodegenerative diseases such as Alzheimer's disease and Down's syndrome. They form a large number of polymorphic structures, including heterogeneous ionic pores in membranes as well as different types of fibrillar and globular structures on surfaces and in solution. Understanding the origin of these structures and the factors that influence their occurrence is of great biomedical interest because of the possible relationship between structure and pathogenicity. Here, we use atomic force microscopy (AFM) and molecular dynamics (MD) simulations to demonstrate that at room temperature a truncated A beta peptide which is generated in vivo and shown to be toxic in vitro forms fibrillar structures on hydrophobic graphite surfaces, but not on hydrophilic mica or lipid bilayers. Our results suggest that the toxic pores and fibrillar polymorphic organizations can be explained in terms of the U-shaped beta-strand-turn-beta-strand structural motif observed for full length A beta and other amyloids, as well as the physicochemical properties at the interfaces. The interactions of the hydrophobic, truncated A beta with its environment illustrate that the universal amyloid motif can provide a link between the pore and fibrillar structures and indicate that surfaces with different physicochemical properties can shift the polymorphic landscape toward other conformational states.
C1 [Jang, Hyunbum; Nussinov, Ruth] SAIC Frederick Inc, Ctr Canc Res, Nanobiol Program, NCI Frederick, Frederick, MD 21702 USA.
[Arce, Fernando Teran; Ramachandran, Srinivasan; Landon, Preston B.; Lal, Ratnesh] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA.
[Arce, Fernando Teran; Ramachandran, Srinivasan; Landon, Preston B.; Lal, Ratnesh] Univ Calif San Diego, Dept Mech & Aerosp Engn, La Jolla, CA 92093 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Inst Mol Med, Dept Human Genet & Mol Med, Sackler Sch Med, IL-69978 Tel Aviv, Israel.
RP Nussinov, R (reprint author), SAIC Frederick Inc, Ctr Canc Res, Nanobiol Program, NCI Frederick, Frederick, MD 21702 USA.
EM ruthnu@helix.nih.gov; rlal@ucsd.edu
FU National Institutes of Health (National Institute on Aging) [AG028709];
National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer
Research
FX This research was supported by the National Institutes of Health
(National Institute on Aging AG028709 to RL). This project has been
funded in whole or in part with Federal funds from the National Cancer
Institute, National Institutes of Health, under contract number
HHSN261200800001E. This research was supported (in part) by the
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research. All simulations had been performed using the
high-performance computational facilities of the Biowulf PC/Linux
cluster at the National Institutes of Health, Bethesda, MD
(http://biowulf.nih.gov).
NR 52
TC 33
Z9 33
U1 2
U2 24
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 1744-683X
EI 1744-6848
J9 SOFT MATTER
JI Soft Matter
PY 2011
VL 7
IS 11
BP 5267
EP 5273
DI 10.1039/c1sm05162h
PG 7
WC Chemistry, Physical; Materials Science, Multidisciplinary; Physics,
Multidisciplinary; Polymer Science
SC Chemistry; Materials Science; Physics; Polymer Science
GA 768LX
UT WOS:000290937300026
PM 21918653
ER
PT J
AU Biering-Sorensen, F
Charlifue, S
DeVivo, MJ
Grinnon, ST
Kleitman, N
Lu, Y
Odenkirchen, J
AF Biering-Sorensen, F.
Charlifue, S.
DeVivo, M. J.
Grinnon, S. T.
Kleitman, N.
Lu, Y.
Odenkirchen, J.
TI Incorporation of the International Spinal Cord Injury Data Set elements
into the National Institute of Neurological Disorders and Stroke Common
Data Elements
SO SPINAL CORD
LA English
DT Article
DE spinal cord injury; International; Data Set; variable names; database
specifications; common data element
ID BASIC DATA SET
AB Objectives: To develop consistent variable names and a common database structure for the data elements in the International Spinal Cord Injury (SCI) Data Sets.
Setting: National Institute of Neurological Disorders and Stroke (NINDS) Common Data Elements (CDE) Project and The Executive Committee of the International SCI Standards and Data Sets committees (ECSCI).
Methods: The NINDS CDE team creates a variable name for each defined data element in the various International SCI Data Sets. Members of the ECSCI review these in an iterative process to make the variable names logical and consistent across the data sets. Following this process, the working group for the particular data set reviews the variable names, and further revisions and adjustments may be made. In addition, a database structure for each data set is developed allowing data to be stored in a uniform way in databases to promote sharing data from different studies.
Results: The International SCI Data Sets variable names and database specifications will be available through the web sites of the International Spinal Cord Society (http://www.iscos.org.uk), the American Spinal Injury Association (http://www.asia-spinalinjury.org) and the NINDS CDE project web site (http://www.CommonDataElements.ninds.nih.gov).
Conclusion: This process will continue as additional International SCI Data Sets fulfill the requirements of the development and approval process and are ready for implementation. Spinal Cord (2011) 49, 60-64; doi: 10.1038/sc.2010.90; published online 24 August 2010
C1 [Biering-Sorensen, F.] Rigshosp, Ctr Neurosci, Clin Spinal Cord Injuries, DK-2100 Copenhagen, Denmark.
[Biering-Sorensen, F.] Univ Copenhagen, Copenhagen, Denmark.
[Charlifue, S.] Craig Hosp, Englewood, CO USA.
[DeVivo, M. J.] Univ Alabama, Dept Phys Med & Rehabil, Birmingham, AL USA.
[Grinnon, S. T.; Lu, Y.] KAI Res Inc, Rockville, MD USA.
[Kleitman, N.; Odenkirchen, J.] NINDS, NIH, Bethesda, MD 20892 USA.
RP Biering-Sorensen, F (reprint author), Rigshosp, Ctr Neurosci, Clin Spinal Cord Injuries, TH2091,Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
EM finbs@rh.regionh.dk
OI Kleitman, Naomi/0000-0003-1089-0257
FU Intramural NIH HHS [Z99 NS999999]
NR 12
TC 18
Z9 20
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1362-4393
J9 SPINAL CORD
JI Spinal Cord
PD JAN
PY 2011
VL 49
IS 1
BP 60
EP 64
DI 10.1038/sc.2010.90
PG 5
WC Clinical Neurology; Rehabilitation
SC Neurosciences & Neurology; Rehabilitation
GA 703QU
UT WOS:000285996800010
PM 20733589
ER
PT J
AU Huestis, MA
Mazzoni, I
Rabin, O
AF Huestis, Marilyn A.
Mazzoni, Irene
Rabin, Olivier
TI Cannabis in Sport Anti-Doping Perspective
SO SPORTS MEDICINE
LA English
DT Review
ID PASSIVE INHALATION; DELTA-9-TETRAHYDROCANNABINOL THC; ENDOCANNABINOID
SYSTEM; URINARY-EXCRETION; MARIJUANA USE; BRAIN REWARD; CIGARETTE-SMOKE;
GC-MS; PERFORMANCE; DRUGS
AB Since 2004, when the World Anti-Doping Agency assumed the responsibility for establishing and maintaining the list of prohibited substances and methods in sport (i.e. the Prohibited List), cannabinoids have been prohibited in all sports during competition. The basis for this prohibition can be found in the World Anti-Doping Code, which defines the three criteria used to consider banning a substance. In this context, we discuss the potential of cannabis to enhance sports performance, the risk it poses to the athlete's health and its violation of the spirit of sport. Although these compounds are prohibited in-competition only, we explain why the pharmacokinetics of their main psychoactive compound, Delta(9)-tetrahydrocannabinol, may complicate the results management of adverse analytical findings. Passive inhalation does not appear to be a plausible explanation for a positive test. Although the prohibition of cannabinoids in sports is one of the most controversial issues in anti-doping, in this review we stress the reasons behind this prohibition, with strong emphasis on the evolving knowledge of cannabinoid pharmacology.
C1 [Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Mazzoni, Irene; Rabin, Olivier] World Antidoping Agcy, Montreal, PQ, Canada.
RP Huestis, MA (reprint author), NIDA, Intramural Res Program, NIH, 251 Bayview Blvd,Suite 05-721, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
FU Intramural NIH HHS [Z01 DA000413-11, ZIA DA000413-12]
NR 135
TC 14
Z9 14
U1 2
U2 17
PU ADIS INT LTD
PI AUCKLAND
PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW
ZEALAND
SN 0112-1642
J9 SPORTS MED
JI Sports Med.
PY 2011
VL 41
IS 11
BP 949
EP 966
PG 18
WC Sport Sciences
SC Sport Sciences
GA 845KU
UT WOS:000296822400004
PM 21985215
ER
PT J
AU Klimke, W
O'Donovan, C
White, O
Brister, JR
Clark, K
Fedorov, B
Mizrachi, I
Pruitt, KD
Tatusova, T
AF Klimke, William
O'Donovan, Claire
White, Owen
Brister, J. Rodney
Clark, Karen
Fedorov, Boris
Mizrachi, Ilene
Pruitt, Kim D.
Tatusova, Tatiana
TI Solving the Problem: Genome Annotation Standards before the data deluge
SO STANDARDS IN GENOMIC SCIENCES
LA English
DT Article
ID ESCHERICHIA-COLI K-12; MINIMUM INFORMATION; MICROBIAL GENOMES; GENETIC
ELEMENTS; RNA GENES; SEQUENCE; RESOURCE; UPDATE; BACTERIA; ARCHIVE
AB The promise of genome sequencing was that the vast undiscovered country would be mapped out by comparison of the multitude of sequences available and would aid researchers in deciphering the role of each gene in every organism. Researchers recognize that there is a need for high quality data. However, different annotation procedures, numerous databases, and a diminishing percentage of experimentally determined gene functions have resulted in a spectrum of annotation quality. NCBI in collaboration with sequencing centers, archival databases, and researchers, has developed the first international annotation standards, a fundamental step in ensuring that high quality complete prokaryotic genomes are available as gold standard references. Highlights include the development of annotation assessment tools, community acceptance of protein naming standards, comparison of annotation resources to provide consistent annotation, and improved tracking of the evidence used to generate a particular annotation. The development of a set of minimal standards, including the requirement for annotated complete prokaryotic genomes to contain a full set of ribosomal RNAs, transfer RNAs, and proteins encoding core conserved functions, is an historic milestone. The use of these standards in existing genomes and future submissions will increase the quality of databases, enabling researchers to make accurate biological discoveries.
C1 [Klimke, William; Brister, J. Rodney; Clark, Karen; Fedorov, Boris; Mizrachi, Ilene; Pruitt, Kim D.; Tatusova, Tatiana] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
[O'Donovan, Claire] European Bioinformat Inst, UniProt, EMBL Outstn, Cambridge CB10 1SD, England.
[White, Owen] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA.
RP Klimke, W (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 45, Bethesda, MD 20894 USA.
OI O'Donovan, Claire/0000-0001-8051-7429
FU National Institutes of Health; National Library of Medicine
FX The authors would like to thank the J. Craig Venter Institute for
hosting the workshop and especially Tanja Davidsen and Ramana Madupu for
help in the organization before, during, and after the workshop. Funding
for the open access charge was provided by the Intramural Research
Program of the National Institutes of Health; National Library of
Medicine.
NR 81
TC 21
Z9 22
U1 1
U2 8
PU GENOMIC STAND CONSORT
PI EAST LANSING
PA MICHIGAN STATE UNIV, GEEO GARRITY, DEPT MICROBIOL, 6162 BIOMED & PHYS
SCI BLDG, EAST LANSING, MI 48824 USA
SN 1944-3277
J9 STAND GENOMIC SCI
JI Stand. Genomic Sci.
PY 2011
VL 5
IS 1
BP 168
EP 193
DI 10.4056/sigs.2084864
PG 26
WC Genetics & Heredity; Microbiology
SC Genetics & Heredity; Microbiology
GA 874GU
UT WOS:000298944200016
PM 22180819
ER
PT J
AU Buckle, AM
Bate, MA
Androulakis, S
Cinquanta, M
Basquin, J
Bonneau, F
Chatterjee, DK
Cittaro, D
Graslund, S
Gruszka, A
Page, R
Suppmann, S
Wheeler, JX
Agostini, D
Taussig, M
Taylor, CF
Bottomley, SP
Villaverde, A
de Marco, A
AF Buckle, Ashley M.
Bate, Mark A.
Androulakis, Steve
Cinquanta, Mario
Basquin, Jerome
Bonneau, Fabien
Chatterjee, Deb K.
Cittaro, Davide
Graslund, Susanne
Gruszka, Alicja
Page, Rebecca
Suppmann, Sabine
Wheeler, Jun X.
Agostini, Deborah
Taussig, Mike
Taylor, Chris F.
Bottomley, Stephen P.
Villaverde, Antonio
de Marco, Ario
TI Recombinant protein quality evaluation: proposal for a minimal
information standard
SO STANDARDS IN GENOMIC SCIENCES
LA English
DT Editorial Material
ID GUIDELINES
C1 [de Marco, Ario] UNG, Dept Environm Sci, Rozna Dolina, Nova Gorica, Slovenia.
[Buckle, Ashley M.; Bate, Mark A.; Bottomley, Stephen P.] Monash Univ, Dept Biochem & Mol Biol, Sch Biomed Sci, Fac Med Nursing & Hlth Sci, Clayton, Vic 3800, Australia.
[Androulakis, Steve] Monash Univ, Monash ERes Ctr, Clayton, Vic, Australia.
[Cinquanta, Mario; Cittaro, Davide; Agostini, Deborah] Cogentech, Prot Chem Unit, Milan, Italy.
[Basquin, Jerome; Bonneau, Fabien] Max Planck Inst Biochem, Dept Struct Cell Biol, D-82152 Martinsried, Germany.
[Chatterjee, Deb K.] NCI, Prot Express Lab, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Graslund, Susanne] Karolinska Inst, Struct Genom Consortium, Dept Med Biophys & Biochem, Stockholm, Sweden.
[Gruszka, Alicja] IEO, Milan, Italy.
[Page, Rebecca] Brown Univ, Dept Mol Biol Cell Biol & Biochem, Providence, RI 02912 USA.
[Suppmann, Sabine] Max Planck Inst Biochem, Microchem Core Facil, D-82152 Martinsried, Germany.
[Taussig, Mike] Babraham Biosci Technol, Prot Technol Grp, Cambridge, England.
[Taylor, Chris F.] European Bioinformat Inst, Hinxton, Cambs, England.
[Villaverde, Antonio] Univ Autonoma Barcelona, Inst Biotechnol & Biomed, E-08193 Barcelona, Spain.
[Villaverde, Antonio] Univ Autonoma Barcelona, Dept Genet & Microbiol, E-08193 Barcelona, Spain.
[Villaverde, Antonio] CIBER Bioingn Biomat & Nanomed CIBER BBN, Barcelona, Spain.
RP de Marco, A (reprint author), UNG, Dept Environm Sci, Rozna Dolina, Nova Gorica, Slovenia.
EM ario.demarco@ung.si
RI Buckle, Ashley/P-8366-2016;
OI Buckle, Ashley/0000-0003-2943-9044; Gruszka, Alicja
M/0000-0002-5359-0281; Cittaro, Davide/0000-0003-0384-3700; Villaverde,
Antonio/0000-0002-2615-4521
FU Biotechnology and Biological Sciences Research Council
[BBS/E/B/0000S178]
NR 21
TC 3
Z9 3
U1 0
U2 10
PU GENOMIC STAND CONSORT
PI EAST LANSING
PA MICHIGAN STATE UNIV, GEEO GARRITY, DEPT MICROBIOL, 6162 BIOMED & PHYS
SCI BLDG, EAST LANSING, MI 48824 USA
SN 1944-3277
J9 STAND GENOMIC SCI
JI Stand. Genomic Sci.
PY 2011
VL 5
IS 2
BP 195
EP 197
DI 10.4056/sigs.1834511
PG 3
WC Genetics & Heredity; Microbiology
SC Genetics & Heredity; Microbiology
GA 874GV
UT WOS:000298944300002
PM 22180821
ER
PT J
AU Bobb, JF
Scharfstein, DO
Daniels, MJ
Collins, FS
Kelada, S
AF Bobb, Jennifer F.
Scharfstein, Daniel O.
Daniels, Michael J.
Collins, Francis S.
Kelada, Samir
TI Multiple Imputation of Missing Phenotype Data for QTL Mapping
SO STATISTICAL APPLICATIONS IN GENETICS AND MOLECULAR BIOLOGY
LA English
DT Article
DE multiple imputation; missing data; quantitative trait loci
ID QUANTITATIVE TRAIT LOCI; AIRWAY RESPONSIVENESS; COLLABORATIVE CROSS;
SYSTEMS GENETICS; INCOMPLETE DATA; MOUSE; MICE; PLETHYSMOGRAPHY;
FRAMEWORK; RESOURCE
AB Missing phenotype data can be a major hurdle to mapping quantitative trait loci (QTL). Though in many cases experiments may be designed to minimize the occurrence of missing data, it is often unavoidable in practice; thus, statistical methods to account for missing data are needed. In this paper we describe an approach for conjoining multiple imputation and QTL mapping. Methods are applied to map genes associated with increased breathing effort in mice after lung inflammation due to allergen challenge in developing lines of the Collaborative Cross, a new mouse genetics resource. Missing data poses a particular challenge in this study because the desired phenotype summary to be mapped is a function of incompletely observed dose-response curves. Comparison of the multiple imputation approach to two naive approaches for handling missing data suggest that these simpler methods may yield poor results: ignoring missing data through a complete case analysis may lead to incorrect conclusions, while using a last observation carried forward procedure, which does not account for uncertainty in the imputed values, may lead to anti-conservative inference. The proposed approach is widely applicable to other studies with missing phenotype data.
C1 [Bobb, Jennifer F.; Scharfstein, Daniel O.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
[Daniels, Michael J.] Univ Florida, Gainesville, FL 32611 USA.
[Collins, Francis S.; Kelada, Samir] NHGRI, NIH, Bethesda, MD USA.
RP Bobb, JF (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
FU National Institutes of Health [R01 CA85295]; National Institute of
Environmental Health Sciences [T32ES012871]; National Human Genome
Research Institute
FX We thank our collaborators Fernando Pardo Manuel de Villena, Elissa
Chesler, Darla Miller, and Ginger Shaw for use of the preCC mice; Gary
Churchill, David Aylor and Will Valdar for advice regarding analysis
approaches; and David Schwartz for input on the allergen model. This
work is supported in part by Award Numbers R01 CA85295 of the National
Institutes of Health, T32ES012871 from the National Institute of
Environmental Health Sciences, and the Intramural Research Program at
the National Human Genome Research Institute.
NR 35
TC 4
Z9 4
U1 0
U2 1
PU BERKELEY ELECTRONIC PRESS
PI BERKELEY
PA 2809 TELEGRAPH AVENUE, STE 202, BERKELEY, CA 94705 USA
SN 1544-6115
J9 STAT APPL GENET MOL
JI Stat. Appl. Genet. Mol. Biol.
PY 2011
VL 10
IS 1
AR 29
DI 10.2202/1544-6115.1676
PG 29
WC Biochemistry & Molecular Biology; Mathematical & Computational Biology;
Statistics & Probability
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology;
Mathematics
GA 787KQ
UT WOS:000292375400001
ER
PT J
AU Yan, LK
Liu, AY
Li, ZH
Zheng, G
AF Yan, Lihan K.
Liu, Aiyi
Li, Zhaohai
Zheng, Gang
TI Optimal two-stage sequential robust design for gene-intervention studies
SO STATISTICS AND ITS INTERFACE
LA English
DT Article
DE Optimal two-stage design; MAX; Group sequential; Gene-intervention
ID GENOME-WIDE ASSOCIATION; CLINICAL-TRIALS; SAMPLE-SIZE; TREND TESTS;
PROPORTIONS; STATISTICS; MAXIMUM; MARKERS; POWER
AB Gene-intervention studies investigate the responsiveness to therapies according to individuals' genetic profiles. We propose a two-stage sequential design for these studies and investigate the cost of the sample size versus the statistical power. In a typical sequential design, a single normally distributed test statistic is used. For a genetic study, the robust test is used because of the uncertainty of the underlying genetic model (e. g. the recessive, additive or dominant models). The robust test statistic that we consider in the two-stage sequential design is the maximum of three correlated normally distributed statistics, each which is optimal under the corresponding genetic model. We study various factors that affect minimizing the average sample number (ASN) or maximizing the power of a gene-intervention study under the two-stage sequential design and make recommendations for the optimal solutions under different scenarios.
C1 [Yan, Lihan K.] US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA.
[Liu, Aiyi] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Rockville, MD USA.
[Li, Zhaohai] George Washington Univ, Dept Stat, Washington, DC 20052 USA.
[Zheng, Gang] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA.
RP Yan, LK (reprint author), US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA.
EM lihan.yan@fda.hhs.gov; liua@mail.nih.gov; zli@gwu.edu;
zhengg@nhlbi.nih.gov
OI Liu, Aiyi/0000-0002-6618-5082
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health
FX We would like to thank the reviewers for their helpful comments which
strengthened the presentation of this paper. We would also like to thank
Ms. Heather Liu for her editorial help. Research of A. Liu is supported
by the Intramural Research Program of the Eunice Kennedy Shriver
National Institute of Child Health and Human Development, National
Institutes of Health. The opinions expressed in the article are those of
the authors, not necessarily of the National Institutes of Health, nor
the Food and Drug Administration.
NR 36
TC 0
Z9 0
U1 0
U2 0
PU INT PRESS BOSTON, INC
PI SOMERVILLE
PA PO BOX 43502, SOMERVILLE, MA 02143 USA
SN 1938-7989
EI 1938-7997
J9 STAT INTERFACE
JI Stat. Interface
PY 2011
VL 4
IS 4
BP 431
EP 441
PG 11
WC Mathematical & Computational Biology; Mathematics, Interdisciplinary
Applications
SC Mathematical & Computational Biology; Mathematics
GA 861DY
UT WOS:000298000500002
ER
PT J
AU Chen, BE
Graubard, BI
Flegal, KM
Gail, MH
AF Chen, Bingshu E.
Graubard, Barry I.
Flegal, Katherine M.
Gail, Mitchell H.
TI Comparing strategies to estimate the association of obesity with
mortality via a Markov model
SO STATISTICS AND ITS INTERFACE
LA English
DT Article
DE Causation; Markov chain; Mortality; Obesity; Reverse causation
ID BODY-MASS INDEX; DEATHS; UNDERWEIGHT; OVERWEIGHT; WEIGHT
AB We used a first order discrete Markov model to investigate strategies to obtain unbiased estimates of the relative mortality hazard for comparing obese with non-obese participants. This hazard ratio is confounded by the fact that obese participants can be either sick or well, as can non-obese participants, and participants can migrate over time from their initial classification on obesity and health status. The parameters of the model were estimated from national survey data and used to illustrate different analytic approaches. The purpose was to compare analytic approaches and not to provide an analysis of a particular data set. Under this model, short term health-stratum-specific estimates are unbiased for estimating the health-stratum-specific instantaneous mortality hazard ratios from obesity, and updating information on body mass index and disease status during long term follow-up reduces bias. For follow-up over 10 or 20 years, exclusion of participants with preexisting disease, excluding the first five years of follow-up, and methods of analysis that ignore health status yield biased estimates of the instantaneous mortality hazard ratios. However, over 10 or 20 year time periods, long-term average mortality hazard ratios or cumulative mortality relative risks are a better reflection of the total impact of obesity, including its tendency to accelerate transitions to sickness under this model, than are instantaneous mortality hazard ratios. Over these longer time periods, average relative hazard estimates or cumulative mortality relative risks based on initially well participants, on initially sick participants, and on the combined initial population each provide valuable descriptions of associations of obesity with mortality.
C1 [Chen, Bingshu E.] Queens Univ, NCIC Clin Trials Grp, Kingston, ON, Canada.
[Chen, Bingshu E.] Queens Univ, Dept Community Hlth & Epidemiol, Kingston, ON, Canada.
[Graubard, Barry I.; Gail, Mitchell H.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Flegal, Katherine M.] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA.
RP Chen, BE (reprint author), Queens Univ, NCIC Clin Trials Grp, Kingston, ON, Canada.
EM bechen@ctg.queensu.ca
RI Flegal, Katherine/A-4608-2013;
OI Chen, Bingshu/0000-0001-6139-0696; Flegal, Katherine/0000-0002-0838-469X
FU Natural Sciences and Engineering Research Council of Canada (NSERC);
National Cancer Institute
FX This work was supported in part by the the Natural Sciences and
Engineering Research Council of Canada (NSERC).; This work was supported
in part by the Intramural Research Program of the National Cancer
Institute.
NR 18
TC 0
Z9 0
U1 0
U2 3
PU INT PRESS BOSTON, INC
PI SOMERVILLE
PA PO BOX 43502, SOMERVILLE, MA 02143 USA
SN 1938-7989
J9 STAT INTERFACE
JI Stat. Interface
PY 2011
VL 4
IS 4
BP 451
EP 461
PG 11
WC Mathematical & Computational Biology; Mathematics, Interdisciplinary
Applications
SC Mathematical & Computational Biology; Mathematics
GA 861DY
UT WOS:000298000500004
ER
PT J
AU Hasebe, T
Buchholz, DR
Shi, YB
Ishizuya-Oka, A
AF Hasebe, Takashi
Buchholz, Daniel R.
Shi, Yun-Bo
Ishizuya-Oka, Atsuko
TI Epithelial-Connective Tissue Interactions Induced by Thyroid Hormone
Receptor Are Essential for Adult Stem Cell Development in the Xenopus
laevis Intestine
SO STEM CELLS
LA English
DT Article
DE Thyroid hormone receptor; Transgenic frog; Organ culture; Tissue
interaction; Intestinal remodeling
ID MATRIX-METALLOPROTEINASE STROMELYSIN-3; ACID-BINDING PROTEIN;
EXTRACELLULAR-MATRIX; GENE-EXPRESSION; SONIC HEDGEHOG; AMPHIBIAN
METAMORPHOSIS; SIGNALING PATHWAY; TADPOLE INTESTINE; PROGENITOR CELLS;
APOPTOSIS
AB In the amphibian intestine during metamorphosis, stem cells appear and generate the adult absorptive epithelium, analogous to the mammalian one, under the control of thyroid hormone (TH). We have previously shown that the adult stem cells originate from differentiated larval epithelial cells in the Xenopus laevis intestine. To clarify whether TH signaling in the epithelium alone is sufficient for inducing the stem cells, we have now performed tissue recombinant culture experiments using transgenic X. laevis tadpoles that express a dominant-positive TH receptor (dpTR) under a control of heat shock promoter. Wild-type (Wt) or dpTR transgenic (Tg) larval epithelium (Ep) was isolated from the tadpole intestine, recombined with homologous or heterologous nonepithelial tissues (non-Ep), and then cultivated in the absence of TH with daily heat shocks to induce transgenic dpTR expression. Adult epithelial progenitor cells expressing sonic hedgehog became detectable on day 5 in both the recombinant intestine of Tg Ep and Tg non-Ep (Tg/Tg) and that of Tg Ep and Wt non-Ep (Tg/Wt). However, in Tg/Wt intestine, they did not express other stem cell markers such as Musashi-1 and never generated the adult epithelium expressing a marker for absorptive epithelial cells. Our results indicate that, while it is unclear why some larval epithelial cells dedifferentiate into adult progenitor/stem cells, TR-mediated gene expression in the surrounding tissues other than the epithelium is required for them to develop into adult stem cells, suggesting the importance of TH-inducible epithelial-connective tissue interactions in establishment of the stem cell niche in the amphibian intestine. STEM CELLS 2011;29:154-161
C1 [Ishizuya-Oka, Atsuko] Nippon Med Sch, Dept Biol, Nakahara Ku, Kanagawa 2110063, Japan.
[Buchholz, Daniel R.] Univ Cincinnati, Dept Biol Sci, Cincinnati, OH 45221 USA.
[Shi, Yun-Bo] NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA.
RP Ishizuya-Oka, A (reprint author), Nippon Med Sch, Dept Biol, Nakahara Ku, 2-297-2 Kosugi Cho, Kanagawa 2110063, Japan.
EM a-oka@nms.ac.jp
FU JSPS [20570060]; NICHD, NIH
FX We thank Dr. Kosuke Kawamura for his kind care to Tg tadpoles and
Mitsuko Kajita for her technical help. This work was supported in part
by the JSPS Grants-in-Aid for Scientific Research (C) (Grant number
20570060 to A.I.-O.) and in part by the Intramural Research Program of
NICHD, NIH (to Y.-B.S.).
NR 52
TC 25
Z9 25
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1066-5099
J9 STEM CELLS
JI Stem Cells
PD JAN
PY 2011
VL 29
IS 1
BP 154
EP 161
DI 10.1002/stem.560
PG 8
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology;
Oncology; Cell Biology; Hematology
SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology
GA 712IF
UT WOS:000286659300017
PM 21280164
ER
PT J
AU Boheler, KR
Joodi, RN
Qiao, H
Juhasz, O
Urick, AL
Chuppa, SL
Gundry, RL
Wersto, RP
Zhou, R
AF Boheler, Kenneth R.
Joodi, Robert N.
Qiao, Hui
Juhasz, Ondrej
Urick, Amanda L.
Chuppa, Sandra L.
Gundry, Rebekah L.
Wersto, Robert P.
Zhou, Rong
TI Embryonic Stem Cell-Derived Cardiomyocyte Heterogeneity and the
Isolation of Immature and Committed Cells for Cardiac Remodeling and
Regeneration
SO STEM CELLS INTERNATIONAL
LA English
DT Article
AB Pluripotent stem cells represent one promising source for cell replacement therapy in heart, but differentiating embryonic stem cell-derived cardiomyocytes (ESC-CMs) are highly heterogeneous and show a variety of maturation states. In this study, we employed an ESC clonal line that contains a cardiac-restricted ncx1 promoter-driven puromycin resistance cassette together with a mass culture system to isolate ESC-CMs that display traits characteristic of very immature CMs. The cells display properties of proliferation, CM-restricted markers, reduced mitochondrial mass, and hypoxia-resistance. Following transplantation into rodent hearts, bioluminescence imaging revealed that immature cells, but not more mature CMs, survived for at least one month following injection. These data and comparisons with more mature cells lead us to conclude that immature hypoxia resistant ESC-CMs can be isolated in mass in vitro and, following injection into heart, form grafts that may mediate long-term recovery of global and regional myocardial contractile function following infarction.
C1 [Boheler, Kenneth R.; Juhasz, Ondrej] NIA, Mol Cardiol & Stem Cell Unit, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA.
[Joodi, Robert N.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Camden, NJ 08103 USA.
[Joodi, Robert N.; Qiao, Hui; Zhou, Rong] Univ Penn, Dept Radiol, Labs Mol Imaging, Philadelphia, PA 19104 USA.
[Urick, Amanda L.; Chuppa, Sandra L.; Gundry, Rebekah L.] Med Coll Wisconsin, Dept Biochem, Milwaukee, WI 53226 USA.
[Urick, Amanda L.; Chuppa, Sandra L.; Gundry, Rebekah L.] Med Coll Wisconsin, Biotechnol & Bioengn Ctr, Milwaukee, WI 53226 USA.
[Wersto, Robert P.] NIA, Resource Res Branch, NIH, Baltimore, MD 21224 USA.
[Zhou, Rong] Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA.
[Zhou, Rong] Univ Penn, Cardiovasc Inst, Philadelphia, PA 19104 USA.
RP Boheler, KR (reprint author), NIA, Mol Cardiol & Stem Cell Unit, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA.
EM bohelerk@grc.nia.nih.gov
FU NIH [R21EB-2473, 4R00HL094798-03, R01-HL081185, R01-HL081185S1];
Innovation Center at the Medical College of Wisconsin; NIH, National
Institute on Aging
FX The research was supported by NIH Grants R21EB-2473 (RZ),
4R00HL094798-03 (RLG), R01-HL081185 (RZ), R01-HL081185S1 (RZ) the
Innovation Center at the Medical College of Wisconsin (RLG), and the
Intramural Research Program (IRP) of the NIH, National Institute on
Aging (KRB, RPW). The authors also thank Dr. M. Celeste Simon for
helping with hypoxic studies.
NR 46
TC 3
Z9 3
U1 0
U2 1
PU HINDAWI PUBLISHING CORPORATION
PI NEW YORK
PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA
SN 1687-966X
J9 STEM CELLS INT
JI Stem Cells Int.
PY 2011
AR UNSP 214203
DI 10.4061/2011/214203
PG 10
WC Cell & Tissue Engineering
SC Cell Biology
GA V29PM
UT WOS:000208760300008
ER
PT J
AU Kania, G
Boheler, KR
Landmesser, U
Wojakowski, W
AF Kania, Gabriela
Boheler, Kenneth R.
Landmesser, Ulf
Wojakowski, Wojciech
TI Stem Cells in Heart Failure
SO STEM CELLS INTERNATIONAL
LA English
DT Editorial Material
C1 [Kania, Gabriela] Univ Zurich, Inst Physiol, CH-8057 Zurich, Switzerland.
[Boheler, Kenneth R.] NIA, NIH, GRC, LCS, Baltimore, MD 21224 USA.
[Landmesser, Ulf] Univ Zurich Hosp, Dept Cardiol, CH-8091 Zurich, Switzerland.
[Wojakowski, Wojciech] Med Univ Silesia, Div Cardiol, PL-40583 Katowice, Poland.
RP Kania, G (reprint author), Univ Zurich, Inst Physiol, Winterthurerstr 190, CH-8057 Zurich, Switzerland.
EM gabriela.kania@uzh.ch
NR 19
TC 0
Z9 0
U1 0
U2 0
PU HINDAWI PUBLISHING CORPORATION
PI NEW YORK
PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA
SN 1687-966X
J9 STEM CELLS INT
JI Stem Cells Int.
PY 2011
AR UNSP 193918
DI 10.4061/2011/193918
PG 3
WC Cell & Tissue Engineering
SC Cell Biology
GA V29PM
UT WOS:000208760300003
ER
PT B
AU Reddy, UM
Willinger, M
AF Reddy, Uma M.
Willinger, Marian
BE Spong, CY
TI Classification of Stillbirths
SO STILLBIRTH: PREDICTION, PREVENTION AND MANAGEMENT
LA English
DT Article; Book Chapter
ID CLASSIFYING PERINATAL DEATH; RELEVANT CONDITION; MORTALITY; SYSTEM
C1 [Reddy, Uma M.; Willinger, Marian] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
RP Reddy, UM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
NR 16
TC 1
Z9 1
U1 0
U2 0
PU BLACKWELL SCIENCE PUBL
PI OXFORD
PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND
BN 978-1-4443-9801-4; 978-1-4443-3706-8
PY 2011
BP 42
EP 54
D2 10.1002/9781444398038
PG 13
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA BA6JA
UT WOS:000337156200004
ER
PT S
AU Oh, J
Nislow, C
AF Oh, Julia
Nislow, Corey
BE Williams, JA
TI Signature-tagged Mutagenesis to Characterize Genes Through Competitive
Selection of Bar-coded Genome Libraries
SO STRAIN ENGINEERING: METHODS AND PROTOCOLS
SE Methods in Molecular Biology
LA English
DT Article; Book Chapter
DE Bar coding; Signature-tagged mutagenesis; Transposon mutagenesis;
TagModules; Deletion collection
ID YEAST DELETION MUTANTS; CANDIDA-ALBICANS; LARGE-SCALE;
STREPTOCOCCUS-PNEUMONIAE; INSERTIONAL MUTAGENESIS; VIRULENCE GENES;
FISSION YEAST; WIDE SCREEN; IDENTIFICATION; DISRUPTION
AB The availability of collections of genome-wide deletion mutants greatly accelerates systematic analyses of gene function. However, each of the thousands of genes that comprise a genome must be phenotyped individually unless they can be assayed in parallel and subsequently deconvolved. To this end, unique molecular identifiers have been developed for a variety of microbes. Specifically, the addition of DNA "tags," or "bar codes," to each mutant allows all mutants in a collection to be pooled and phenotyped in parallel, greatly increasing experimental throughput. In this chapter, we provide an overview of current methodologies used to create such tagged mutant collections and outline how they can be applied to understand gene function, gene-gene interactions, and drug-gene interactions. Finally, we present a methodology that uses universal TagModules, capable of bar coding a wide range of microorganisms, and demonstrate its reduction to practice by creating tagged mutant collections in the pathogenic yeast Candida albicans.
C1 [Oh, Julia] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
[Nislow, Corey] Donnelly Ctr, Donnelly Sequencing Ctr, Toronto, ON, Canada.
RP Oh, J (reprint author), NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
OI Nislow, Corey/0000-0002-4016-8874
FU CGH CDC HHS [P01 GH000205]; Canadian Institutes of Health Research
[MOP-84305]; NHGRI NIH HHS [HG000205, R01 HG003317, T32 HG00044]
NR 40
TC 2
Z9 2
U1 0
U2 4
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA
SN 1064-3745
BN 978-1-61779-196-3
J9 METHODS MOL BIOL
JI Methods Mol. Biol.
PY 2011
VL 765
BP 225
EP 252
DI 10.1007/978-1-61779-197-0_14
D2 10.1007/978-1-61779-197-0
PG 28
WC Biochemical Research Methods; Biochemistry & Molecular Biology; Genetics
& Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA BWE71
UT WOS:000293772200014
PM 21815096
ER
PT S
AU Bhagwat, M
Bhagwat, AA
AF Bhagwat, Medha
Bhagwat, Arvind A.
BE Williams, JA
TI Microbial Genome Analysis and Comparisons: Web-Based Protocols and
Resources
SO STRAIN ENGINEERING: METHODS AND PROTOCOLS
SE Methods in Molecular Biology
LA English
DT Article; Book Chapter
DE Pairwise genome comparisons; Bioinformatics tools; Microbial genome
resources
ID ACID RESISTANCE; DATABASE
AB Fully annotated genome sequences of many microorganisms are publicly available as a resource. However, in-depth analysis of these genomes using specialized tools is required to derive meaningful information. We describe here the utility of three powerful publicly available genome databases and analysis tools. Protocols outlined here are particularly useful for performing pairwise genome comparisons between closely related microorganisms to identify similarities and unique features, for example to identify genes specific to a pathogenic strain of Escherichia coli compared to a nonpathogenic strain.
C1 [Bhagwat, Medha] NIH, NIH Lib, Off Res Serv, Bethesda, MD 20892 USA.
[Bhagwat, Arvind A.] USDA, Environm Microbial & Food Safety Lab, Beltsville, MD 20705 USA.
[Bhagwat, Arvind A.] Org USDA ARS, Div Environm Microbial & Food Safety Lab, Beltsville, MD USA.
RP Bhagwat, M (reprint author), NIH, NIH Lib, Off Res Serv, Bldg 10, Bethesda, MD 20892 USA.
NR 14
TC 0
Z9 0
U1 0
U2 0
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA
SN 1064-3745
BN 978-1-61779-196-3
J9 METHODS MOL BIOL
JI Methods Mol. Biol.
PY 2011
VL 765
BP 297
EP 307
DI 10.1007/978-1-61779-197-0_17
D2 10.1007/978-1-61779-197-0
PG 11
WC Biochemical Research Methods; Biochemistry & Molecular Biology; Genetics
& Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA BWE71
UT WOS:000293772200017
PM 21815099
ER
PT J
AU Roper, JA
O'Carroll, AM
Young, WS
Lolait, SJ
AF Roper, J. A.
O'Carroll, A-M
Young, W. S., III
Lolait, S. J.
TI The vasopressin Avpr1b receptor: Molecular and pharmacological studies
SO STRESS-THE INTERNATIONAL JOURNAL ON THE BIOLOGY OF STRESS
LA English
DT Review
DE Aggression; hypothalamic-pituitary-adrenal axis; stress; Avpr1b
receptor; Avpr1b antagonist; vasopressin
ID PITUITARY-ADRENAL AXIS; CORTICOTROPIN-RELEASING HORMONE; INSULIN-INDUCED
HYPOGLYCEMIA; DEFICIENT BRATTLEBORO RATS; MESSENGER-RIBONUCLEIC-ACID;
STRESS-RELATED DISORDERS; CENTRAL-NERVOUS-SYSTEM; ARGININE-VASOPRESSIN;
V-1B RECEPTOR; V1B RECEPTOR
AB The distribution, pharmacology and function of the arginine vasopressin (Avp) 1b receptor subtype (Avpr1b) has proved more challenging to investigate compared to other members of the Avp receptor family. Avp is increasingly recognised as an important modulator of the hypothalamic-pituitary-adrenal (HPA) axis, an action mediated by the Avpr1b present on anterior pituitary corticotrophs. The Avpr1b is also expressed in some peripheral tissues including pancreas and adrenal, and in the hippocampus (HIP), paraventricular nucleus and olfactory bulb of the rodent brain where its function is unknown. The central distribution of Avpr1bs is far more restricted than that of the Avpr1a, the main Avp receptor subtype found in the brain. Whether Avpr1b expression in rodent tissues is dependent on differences in the length of microsatellite dinucleotide repeats present in the 5' promoter region of the Avpr1b gene remains to be determined. One difficulty of functional studies on the Avpr1b, especially its involvement in the HPA axis response to stress, which prompted the generation of Avpr1b knockout (KO) mouse models, was the shortage of commercially available Avpr1b ligands, particularly antagonists. Research on mice lacking functional Avpr1bs has highlighted behavioural deficits in social memory and aggression. The Avpr1b KO also appears to be an excellent model to study the contribution of the Avpr1b in the HPA axis response to acute and perhaps some chronic (repeated) stressors where corticotrophin-releasing hormone and other genes involved in the HPA axis response to stress do not appear to compensate for the loss of the Avpr1b.
C1 [Roper, J. A.; O'Carroll, A-M; Lolait, S. J.] Univ Bristol, Henry Wellcome LINE, Bristol BS1 3NY, Avon, England.
[Young, W. S., III] NIMH, Sect Neural Gene Express, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
RP Lolait, SJ (reprint author), Univ Bristol, Henry Wellcome LINE, Dorothy Hodgkin Bldg,Whitson St, Bristol BS1 3NY, Avon, England.
EM s.j.lolait@bristol.ac.uk
RI Young, W Scott/A-9333-2009
OI Young, W Scott/0000-0001-6614-5112
FU Neuroendocrinology Charitable Trust (UK); Schering-Plough Corporation;
Wellcome Trust; BBSRC; NIMH [Z01-MH-002498-21]
FX J.A.R received funding from the Neuroendocrinology Charitable Trust (UK)
and the Schering-Plough Corporation; A.M.O'C received funding from the
Wellcome Trust and BBSRC. This research was supported by the NIMH
Intramural Research Program (Z01-MH-002498-21). S.J.L received funding
from the Wellcome Trust.
NR 136
TC 34
Z9 35
U1 1
U2 10
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1025-3890
J9 STRESS
JI Stress
PD JAN
PY 2011
VL 14
IS 1
BP 98
EP 115
DI 10.3109/10253890.2010.512376
PG 18
WC Behavioral Sciences; Endocrinology & Metabolism; Neurosciences
SC Behavioral Sciences; Endocrinology & Metabolism; Neurosciences &
Neurology
GA 696DP
UT WOS:000285422400013
PM 20828336
ER
PT J
AU Ginsberg, MD
Palesch, YY
Martin, RH
Hill, MD
Moy, CS
Waldman, BD
Yeatts, SD
Tamariz, D
Ryckborst, K
AF Ginsberg, Myron D.
Palesch, Yuko Y.
Martin, Renee H.
Hill, Michael D.
Moy, Claudia S.
Waldman, Bonnie D.
Yeatts, Sharon D.
Tamariz, Diego
Ryckborst, Karla
CA ALIAS Investigators
TI The Albumin in Acute Stroke (ALIAS) Multicenter Clinical Trial Safety
Analysis of Part 1 and Rationale and Design of Part 2
SO STROKE
LA English
DT Article
DE albumin; ischemic stroke; neuroprotectant; randomized controlled trial
ID FOCAL CEREBRAL-ISCHEMIA; MARKED NEUROPROTECTIVE EFFICACY; LOCAL VASCULAR
DYNAMICS; DOSE-ESCALATION; BRAIN-INJURY; PILOT TRIAL; RAT MODEL;
THERAPY; RESPONSES; THROMBOSIS
AB Background and Purpose-Enrollment in the Albumin in Acute Stroke (ALIAS) Trial was suspended in late 2007 due to a safety concern. We present the safety data of that Trial ("Part 1") and the rationale for the design of Part 2.
Methods-ALIAS Part 1 was designed to assess whether 25% albumin (ALB) started within 5 hours of stroke onset would confer neuroprotection in subjects with acute ischemic stroke and baseline National Institutes of Health Stroke Scale of >= 6. Exclusion criteria included recent or current congestive heart failure, myocardial infarction, or cardiac surgery. The study comprised 2 cohorts: subjects who received thrombolysis and those who did not, each with 1:1 randomization to ALB or placebo. The primary outcome was the National Institutes of Health Stroke Scale and modified Rankin Scales at 90 days. The intended sample size was 1800.
Results-Four hundred thirty-four subjects were enrolled, and 424 were used in the safety analysis (ALB 207, saline 217). There were 36 deaths within the first 30 days in the ALB group and 21 in the saline group. In contrast, death rates after 30 days were similar by treatment. Large strokes were the predominant cause of early death in both groups. In subjects >83 years of age, 90-day death rates were 2.3-fold higher with ALB than with saline (95% CI, 1.04 to 5.12). Similarly, 90-day deaths in subjects receiving excessive fluids were 2.10-fold greater with ALB than with saline (CI, 1.10 to 3.98).
Conclusions-The ALIAS Part 2 Trial, which started in early 2009, was modified as follows to enhance safety: upper age limit of 83 years; requirement for normal baseline serum troponin level; restriction of total intravenous fluids in the first 48 hours to <= 4200 mL; mandatory diuretic at 12 to 24 hours; and detailed site retraining. Because of insufficient nonthrombolysed subjects (22%) in Part 1, the 2-cohort design was eliminated. The Data Safety Monitoring Board has reviewed the safety data of Part 2 3 times and has approved continuation of the trial. (Stroke. 2011;42:119-127.)
C1 [Ginsberg, Myron D.; Tamariz, Diego] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33101 USA.
[Hill, Michael D.; Ryckborst, Karla] Univ Calgary, Foothills Med Ctr, Calgary, AB, Canada.
[Hill, Michael D.] Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada.
[Palesch, Yuko Y.; Martin, Renee H.; Waldman, Bonnie D.; Yeatts, Sharon D.] Med Univ S Carolina, Dept Med, Div Biostat & Epidemiol, Charleston, SC 29425 USA.
[Moy, Claudia S.] NINDS Off Clin Res, Bethesda, MD USA.
RP Ginsberg, MD (reprint author), Univ Miami, Miller Sch Med, Dept Neurol D4 5, POB 016960, Miami, FL 33101 USA.
EM mginsberg@med.miami.edu
OI Hill, Michael/0000-0002-6269-1543
FU National Institutes of Health [U01 NS040406, U01 NS054630]
FX Supported by National Institutes of Health grants U01 NS040406 (to
M.D.G.) and U01 NS054630 (to Y.Y.P.).
NR 33
TC 38
Z9 41
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD JAN
PY 2011
VL 42
IS 1
BP 119
EP 127
DI 10.1161/STROKEAHA.110.596072
PG 9
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 699AN
UT WOS:000285636400027
PM 21164127
ER
PT B
AU Fabre, K
DeGraff, W
Cook, JA
Krishna, MC
Mitchell, JB
AF Fabre, Kristin
DeGraff, William
Cook, John A.
Krishna, Murali C.
Mitchell, James B.
BE Basu, S
Wiklund, L
TI Experimental Models for Ionizing Radiation Research
SO STUDIES ON EXPERIMENTAL MODELS
SE Oxidative Stress in Applied Basic Research and Clinical Practice
LA English
DT Article; Book Chapter
DE Cell killing; DNA damage; DNA repair; IR protectors; Radiation;
Radiosensitizers; ROS
ID DOUBLE-STRAND BREAKS; INDUCED GENOMIC INSTABILITY; SOMATIC
MAMMALIAN-CELLS; CHINESE-HAMSTER-CELLS; DNA-REPAIR; ALPHA-PARTICLES;
LUNG-CANCER; INTRACELLULAR SUPEROXIDE; DEINOCOCCUS-RADIODURANS;
GEL-ELECTROPHORESIS
AB Ionizing radiation is a valuable tool used for cancer treatment as well as for basic molecular research. More recent interest stems from a need to provide countermeasures against accidental or intentional exposure to radiation through nuclear devices. This chapter provides an overview of the biological effects of radiation and highlights models used to study radiation-induced damage and repair. In vitro and in vivo endpoints including DNA damage, cell survival, apoptosis, cytogenetic aberrations, oxidative stress, tumor response, and genomic instability are discussed. Appropriate use of these models will facilitate the advancement of radiation research as novel molecular mechanisms are elucidated.
C1 [Fabre, Kristin; DeGraff, William; Cook, John A.; Krishna, Murali C.; Mitchell, James B.] NCI, Radiat Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Krishna, MC (reprint author), NCI, Radiat Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
EM murali@helix.nih.gov
NR 127
TC 0
Z9 0
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES
BN 978-1-60761-955-0
J9 OXID STRESS APPL BAS
JI Oxid. Stress Appl. Basic Res. Clin. Pract.
PY 2011
BP 371
EP 397
DI 10.1007/978-1-60761-956-7_17
D2 10.1007/978-1-60761-956-7
PG 27
WC Biochemistry & Molecular Biology; Medicine, General & Internal
SC Biochemistry & Molecular Biology; General & Internal Medicine
GA BVJ58
UT WOS:000291666700017
ER
PT J
AU Dell, CA
Gust, SW
MacLean, S
AF Dell, Colleen Anne
Gust, Steven W.
MacLean, Sarah
TI Global Issues in Volatile Substance Misuse INTRODUCTION
SO SUBSTANCE USE & MISUSE
LA English
DT Editorial Material
DE volatile substance misuse; inhalants; sociocultural epidemiology;
neuroscience; interventions; context-specific knowledge; huffing;
cuffing; chroming; bagging
ID INHALANT USE; ABUSE; ADOLESCENTS
AB This special issue of Substance Use & Misuse addresses the public health issue of volatile substance misuse (VSM), the inhalation of gases or vapors for psychoactive effects, assessing the similarities and differences in the products misused, patterns, prevalence, etiologies, and impacts of VSM by examining it through sociocultural epidemiology, neuroscience, and interventions research. The Canadian, US, and Australian guest editors contend that, when compared with other drugs used at a similar prevalence, VSM has attracted relatively little research effort. The authors and editors call for further research to develop evidence-based policies and comprehensive interventions that respect culture and context-specific knowledge.0.35 and >2.0 ng/mL/y have been associated with an increased risk of prostate cancer (CaP) death more than 10 years and 1 year before diagnosis, respectively. It is unknown how frequently PSAVs of this magnitude occur in community men.
METHODS From the Baltimore Longitudinal Study of Aging, we examined the PSAV distribution in 786 men with serial PSA measurements (3474 PSAV observations) at total PSA levels <10 ng/mL. We also determined whether PSAV altered the probability of overall and life-threatening CaP at PSA levels <3 and 3-10 ng/mL.
RESULTS Overall, the mean PSA and PSAV were 1.3 ng/mL and 0.05 ng/mL/y, respectively. PSAV rose continuously with increasing PSA (P < .0001), and was significantly higher in cancers than controls for observations at PSA levels <3 ng/mL (P = .02) and 3-10 ng/mL (P = .0008). The probability of life-threatening CaP was 3% at a PSA <3 ng/mL, but increased to 13.6% with PSAV >0.4 ng/mL/y. At PSA levels of 3-10 ng/mL, the probability of life-threatening CaP was 9.8% based on PSA alone vs 12% with PSAV >0.4 ng/mL/y.
CONCLUSIONS PSAV was significantly higher in CaP observations than controls in all PSA ranges studied and altered the risk of overall and life-threatening CaP at a given PSA level. Because the value of PSAV is PSA-dependent, the PSA level should be taken into account when interpreting PSAV. UROLOGY 77: 143-148, 2011. (C) 2011 Published by Elsevier Inc.
C1 Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA.
NIA, NIH, Clin Res Branch, Baltimore, MD 21224 USA.
RP Loeb, S (reprint author), Johns Hopkins Brady Urol Inst, 600 N Wolfe St,Marburg 1, Baltimore, MD 21287 USA.
EM stacyloeb@gmail.com
OI Loeb, Stacy/0000-0003-3933-9207
FU NIH, National Institute on Aging
FX This research was supported by the Intramural Research Program of the
NIH, National Institute on Aging.
NR 19
TC 10
Z9 10
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0090-4295
J9 UROLOGY
JI Urology
PD JAN
PY 2011
VL 77
IS 1
BP 143
EP 147
DI 10.1016/j.urology.2010.04.068
PG 5
WC Urology & Nephrology
SC Urology & Nephrology
GA 700XM
UT WOS:000285778800044
PM 21195835
ER
PT S
AU Griffon, N
Soualmia, LF
Neveol, A
Massari, P
Thirion, B
Dahamna, B
Darmoni, SJ
AF Griffon, Nicolas
Soualmia, Lina F.
Neveol, Aurelie
Massari, Philippe
Thirion, Benoit
Dahamna, Badisse
Darmoni, Stefan J.
BE Moen, A
Andersen, SK
Aarts, J
Hurlen, P
TI Evaluation of Multi-Terminology Super-Concepts for Information Retrieval
SO USER CENTRED NETWORKED HEALTH CARE
SE Studies in Health Technology and Informatics
LA English
DT Proceedings Paper
CT 23 rd Conference of the European Federation of Medical Informatics (MIE)
CY AUG 28-31, 2011
CL Forum Databehandling Helsesektoren, Oslo, NORWAY
SP European Federat Med Informat
HO Forum Databehandling Helsesektoren
DE abstracting and indexing; cataloguing; information storage and
retrieval; internet; controlled vocabulary
AB Background: Following a recent change in the indexing policy for French quality controlled health gateway CISMeF, multiple terminologies are now being used for indexing in addition to MeSH (R). Objective: To evaluate precision and recall of super-concepts for information retrieval in a multi-terminology paradigm compared to MeSH-only. Methods: We evaluate the relevance of resources retrieved by multi-terminology super-concepts and MeSH-only super-concepts queries. Results: Recall was 8-14% higher for multi-terminology super-concepts compared to MeSH only super-concepts. Precision decreased from 0.66 for MeSH only super-concepts to 0.61 for multi-terminology super-concepts. Retrieval performance was found to vary significantly depending on the super-concepts (p<10(-4)) and indexing methods (manual vs automatic; p<0.004). Conclusion: A multi-terminology paradigm contributes to increase recall but lowers precision. Automated tools for indexing are not accurate enough to allow a very precise information retrieval.
C1 [Griffon, Nicolas; Massari, Philippe; Thirion, Benoit; Dahamna, Badisse; Darmoni, Stefan J.] Rouen Univ Hosp, CISMeF, 1 Rue Germont, F-76031 Rouen, France.
[Soualmia, Lina F.; Thirion, Benoit; Dahamna, Badisse; Darmoni, Stefan J.] Univ Rouen, BTIBS LITIS, EA 4108, Rouen, France.
[Soualmia, Lina F.] Univ Paris 13, LIM&Bio, F-93430 Villetaneuse, France.
[Neveol, Aurelie] NLM, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
RP Darmoni, SJ (reprint author), Rouen Univ Hosp, CISMeF, 1 Rue Germont, F-76031 Rouen, France.
EM stefan.darmoni@chu-rouen.fr
RI Stefan, Darmoni/H-4554-2016;
OI Soualmia, Lina F/0000-0001-7668-2819
NR 10
TC 1
Z9 1
U1 0
U2 0
PU IOS PRESS
PI AMSTERDAM
PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS
SN 0926-9630
BN 978-1-60750-806-9
J9 STUD HEALTH TECHNOL
PY 2011
VL 169
BP 492
EP 496
DI 10.3233/978-1-60750-806-9-492
PG 5
WC Health Care Sciences & Services; Medical Informatics
SC Health Care Sciences & Services; Medical Informatics
GA BA4DP
UT WOS:000335401700096
PM 21893798
ER
PT B
AU Keith, JM
AF Keith, Jerry M.
BE Rappuoli, R
Bagnoli, F
TI Bacterial Protein Toxins Used in Vaccines
SO VACCINE DESIGN: INNOVATIVE APPROACHES AND NOVEL STRATEGIES
LA English
DT Article; Book Chapter
ID ACELLULAR PERTUSSIS VACCINES; SITE-DIRECTED MUTAGENESIS; TOBACCO MOSAIC
VIRUS; AMINO-ACID-SEQUENCE; DIPHTHERIA-TOXIN; TETANUS TOXIN;
BORDETELLA-PERTUSSIS; WHOOPING-COUGH; NUCLEOTIDE-SEQUENCE;
ESCHERICHIA-COLI
AB At first glance, the idea of using protein toxins as vaccines against bacterial human diseases seems somewhat of a paradox. However, in some diseases, the severe pathological effects manifested by the causative agents are mediated entirely by protein toxins. Thus, it seems reasonable to expect that if antibodies could be induced against the protein toxin, they should be effective at preventing severe disease. Of course, the obvious challenge is to detoxify the protein toxin activity without destroying its ability to induce neutralizing antibodies. From an academic point of view, it is ironic that early vaccines against diphtheria, tetanus, and whooping cough were successful without understanding what made them work. One of the keys to this puzzle was uncovered quite by accident when it was discovered that diphtheria toxin stock preparations stored in large earthenware jars too large to be autoclaved were being detoxified by the residual formalin that leached into the preparations from the formalin-sterilized jars. It took two decades for this discovery to be understood and appreciated to a point at which formalin treatment could be applied to produce toxoid preparations for vaccination. It then took another half a century to develop the scientific tools and knowledge needed to bring forth the new generation of vaccines, which are highly effective and less reactogenic. This chapter traces the scientific history, controversies, and development of diphtheria, tetanus and pertussis vaccines.
C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Keith, JM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
EM keithjer@mail.nih.gov
NR 199
TC 1
Z9 1
U1 0
U2 0
PU CAISTER ACADEMIC PRESS
PI WYMONDHAM
PA 32 HEWITTS LANE, WYMONDHAM NR 18 0JA, ENGLAND
BN 978-1-904455-74-5
PY 2011
BP 109
EP 137
PG 29
WC Immunology; Microbiology
SC Immunology; Microbiology
GA BSI02
UT WOS:000284505400006
ER
PT J
AU Webster, JD
Dennis, MM
Dervisis, N
Heller, J
Bacon, NJ
Bergman, PJ
Bienzle, D
Cassali, G
Castagnaro, M
Cullen, J
Esplin, DG
Pena, L
Goldschmidt, MH
Hahn, KA
Henry, CJ
Hellmen, E
Kamstock, D
Kirpensteijn, J
Kitchell, BE
Amorim, RL
Lenz, SD
Lipscomb, TP
McEntee, M
McGill, LD
McKnight, CA
McManus, PM
Moore, AS
Moore, PF
Moroff, SD
Nakayama, H
Northrup, NC
Sarli, G
Scase, T
Sorenmo, K
Schulman, FY
Shoieb, AM
Smedley, RC
Spangler, WL
Teske, E
Thamm, DH
Valli, VE
Vernau, W
von Euler, H
Withrow, SJ
Weisbrode, SE
Yager, J
Kiupel, M
AF Webster, J. D.
Dennis, M. M.
Dervisis, N.
Heller, J.
Bacon, N. J.
Bergman, P. J.
Bienzle, D.
Cassali, G.
Castagnaro, M.
Cullen, J.
Esplin, D. G.
Pena, L.
Goldschmidt, M. H.
Hahn, K. A.
Henry, C. J.
Hellmen, E.
Kamstock, D.
Kirpensteijn, J.
Kitchell, B. E.
Amorim, R. L.
Lenz, S. D.
Lipscomb, T. P.
McEntee, M.
McGill, L. D.
McKnight, C. A.
McManus, P. M.
Moore, A. S.
Moore, P. F.
Moroff, S. D.
Nakayama, H.
Northrup, N. C.
Sarli, G.
Scase, T.
Sorenmo, K.
Schulman, F. Y.
Shoieb, A. M.
Smedley, R. C.
Spangler, W. L.
Teske, E.
Thamm, D. H.
Valli, V. E.
Vernau, W.
von Euler, H.
Withrow, S. J.
Weisbrode, S. E.
Yager, J.
Kiupel, M.
TI Recommended Guidelines for the Conduct and Evaluation of Prognostic
Studies in Veterinary Oncology
SO VETERINARY PATHOLOGY
LA English
DT Article
DE cancer; guidelines; prognostication; standardization; veterinary
oncology
ID MAST-CELL TUMORS; MULTIVARIATE DATA-ANALYSIS; MINIMUM INFORMATION;
SURVIVAL ANALYSIS; APPENDICULAR OSTEOSARCOMA; PROTEIN EXPRESSION;
CONSORT STATEMENT; DOGS; IMMUNOHISTOCHEMISTRY; QUALITY
AB There is an increasing need for more accurate prognostic and predictive markers in veterinary oncology because of an increasing number of treatment options, the increased financial costs associated with treatment, and the emotional stress experienced by owners in association with the disease and its treatment. Numerous studies have evaluated potential prognostic and predictive markers for veterinary neoplastic diseases, but there are no established guidelines or standards for the conduct and reporting of prognostic studies in veterinary medicine. This lack of standardization has made the evaluation and comparison of studies difficult. Most important, translating these results to clinical applications is problematic. To address this issue, the American College of Veterinary Pathologists' Oncology Committee organized an initiative to establish guidelines for the conduct and reporting of prognostic studies in veterinary oncology. The goal of this initiative is to increase the quality and standardization of veterinary prognostic studies to facilitate independent evaluation, validation, comparison, and implementation of study results. This article represents a consensus statement on the conduct and reporting of prognostic studies in veterinary oncology from veterinary pathologists and oncologists from around the world. These guidelines should be considered a recommendation based on the current state of knowledge in the field, and they will need to be continually reevaluated and revised as the field of veterinary oncology continues to progress. As mentioned, these guidelines were developed through an initiative of the American College of Veterinary Pathologists' Oncology Committee, and they have been reviewed and endorsed by the World Small Animal Veterinary Association.
C1 [Smedley, R. C.; Kiupel, M.] Michigan State Univ, Coll Vet Med, Diagnost Ctr Populat & Anim Hlth, E Lansing, MI 48824 USA.
[Webster, J. D.] NCI, Mol Pathol Unit, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Dennis, M. M.] Univ Sydney, Fac Vet Sci, Camden, NSW, Australia.
[Dervisis, N.; Kitchell, B. E.] Michigan State Univ, Coll Vet Med, Dept Small Anim Clin Sci, E Lansing, MI 48824 USA.
[Heller, J.] Charles Sturt Univ, Sch Anim & Vet Sci, Wagga Wagga, NSW, Australia.
[Bacon, N. J.] Univ Florida, Coll Vet Med, Dept Small Anim Clin Sci, Gainesville, FL 32610 USA.
[Bergman, P. J.] BrightHeart Vet Ctr, Armonk, NY USA.
[Bienzle, D.] Univ Guelph, Dept Pathobiol, Guelph, ON N1G 2W1, Canada.
[Cassali, G.] Univ Fed Minas Gerais, Inst Biol Sci, Dept Gen Pathol, Belo Horizonte, MG, Brazil.
[Castagnaro, M.] Univ Padua, Dept Publ Hlth Comparat Pathol & Vet Hyg, Padua, Italy.
[Cullen, J.] N Carolina State Univ, Coll Vet Med, Dept Populat Hlth & Pathobiol, Raleigh, NC USA.
[Esplin, D. G.; McGill, L. D.] ARUP Labs, Salt Lake City, UT USA.
[Pena, L.] Univ Complutense Madrid, Sch Vet, Dept Anim Med Surg & Pathol, Madrid, Spain.
[Goldschmidt, M. H.] Univ Penn, Sch Vet Med, Dept Pathobiol, Philadelphia, PA 19104 USA.
[Hahn, K. A.] Hills Pet Nutr Inc, Topeka, KS USA.
[Henry, C. J.] Univ Missouri, Coll Vet Med, Dept Vet Med & Surg, Columbia, MO 65211 USA.
[Hellmen, E.] Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, Uppsala, Sweden.
[Kamstock, D.] Colorado State Univ, Coll Vet Med, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA.
[Kirpensteijn, J.; Teske, E.] Univ Utrecht, Fac Vet Med, Dept Compan Anim Sci, Utrecht, Netherlands.
[Amorim, R. L.] Sao Paulo State Univ, UNESP, Sch Vet Med, Dept Vet Clin, Sao Paulo, Brazil.
[Lenz, S. D.] Purdue Univ, Sch Vet Med, Dept Comparat Pathobiol, W Lafayette, IN 47907 USA.
[Lipscomb, T. P.; Schulman, F. Y.] Armed Forces Inst Pathol, Dept Vet Pathol, Washington, DC 20306 USA.
[McEntee, M.] Cornell Univ, Coll Vet Med, Dept Clin Sci, Ithaca, NY 14853 USA.
[McKnight, C. A.] MPI Res, Mattawan, MI USA.
[McManus, P. M.] Idexx Reference Labs, Portland, OR USA.
[Moore, A. S.] Univ Sydney, Fac Vet Sci, Sydney, NSW 2006, Australia.
[Moore, P. F.; Vernau, W.] Univ Calif Davis, Sch Vet Med, Dept Pathol Microbiol & Immunol, Davis, CA 95616 USA.
[Moroff, S. D.] Antech Diagnost, Lake Success, NY USA.
[Nakayama, H.] Univ Tokyo, Grad Sch Agr & Life Sci, Tokyo, Japan.
[Northrup, N. C.] Univ Georgia, Coll Vet Med, Dept Small Anim Med & Surg, Athens, GA USA.
[Sarli, G.] Univ Bologna, Fac Vet Med, Dept Vet Publ Hlth & Anim Pathol, Bologna, Italy.
[Scase, T.] Bridge Pathol Ltd, Bristol, Avon, England.
[Sorenmo, K.] Univ Penn, Sch Vet Med, Ryan Vet Hosp, Philadelphia, PA 19104 USA.
[Shoieb, A. M.] Pfizer Ltd, Drug Safety & Res Dev, Sandwich CT13 9NJ, Kent, England.
[Spangler, W. L.] NSG Pathol, Winters, CA USA.
[Thamm, D. H.; Withrow, S. J.] Colorado State Univ, Anim Canc Ctr, Ft Collins, CO 80523 USA.
[Valli, V. E.] VDx Vet Diagnost, Davis, CA USA.
[von Euler, H.] Swedish Univ Agr Sci, Dept Clin Sci, Uppsala, Sweden.
[Weisbrode, S. E.] Ohio State Univ, Coll Vet Med, Dept Vet Biosci, Columbus, OH 43210 USA.
[Yager, J.] Yager Best Histovet, Guelph, ON, Canada.
[Kiupel, M.] Michigan State Univ, Coll Vet Med, Dept Pathobiol & Diagnost Invest, E Lansing, MI 48824 USA.
RP Kiupel, M (reprint author), Michigan State Univ, Diagnost Ctr Populat & Anim Hlth, 4125 Beaumont Rd 152A, Lansing, MI 48910 USA.
EM kiupel@dcpah.msu.edu
RI Medicina Molecular, Inct/J-8737-2013; Pena, Laura/M-7820-2014; Thamm,
Douglas/I-5976-2013; Heller, Jane/H-9596-2016; Dervisis,
Nikolaos/K-8931-2016;
OI Pena, Laura/0000-0001-7135-6280; Thamm, Douglas/0000-0002-8914-7767;
Heller, Jane/0000-0003-3993-0160; Dervisis,
Nikolaos/0000-0003-2869-1483; Goldschmidt, Michael/0000-0001-9515-0535;
, Carolyn/0000-0002-2761-5203
FU American College of Veterinary Pathologists' Oncology Committee; World
Small Animal Veterinary Association
FX These guidelines were developed through an initiative of the American
College of Veterinary Pathologists' Oncology Committee and represent the
consensus opinion of the committee and the listed authors. The
guidelines have also been reviewed and endorsed by the World Small
Animal Veterinary Association. We would like to thank both organizations
for their support and guidance.
NR 60
TC 29
Z9 29
U1 1
U2 6
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0300-9858
J9 VET PATHOL
JI Vet. Pathol.
PD JAN
PY 2011
VL 48
IS 1
BP 7
EP 18
DI 10.1177/0300985810377187
PG 12
WC Pathology; Veterinary Sciences
SC Pathology; Veterinary Sciences
GA 719JH
UT WOS:000287200500002
PM 20664014
ER
PT J
AU Kiupel, M
Webster, JD
Bailey, KL
Best, S
DeLay, J
Detrisac, CJ
Fitzgerald, SD
Gamble, D
Ginn, PE
Goldschmidt, MH
Hendrick, MJ
Howerth, EW
Janovitz, EB
Langohr, I
Lenz, SD
Lipscomb, TP
Miller, MA
Misdorp, W
Moroff, S
Mullaney, TP
Neyens, I
O'Toole, D
Ramos-Vara, J
Scase, TJ
Schulman, FY
Sledge, D
Smedley, RC
Smith, K
Snyder, PW
Southorn, E
Stedman, NL
Steficek, BA
Stromberg, PC
Valli, VE
Weisbrode, SE
Yager, J
Heller, J
Miller, R
AF Kiupel, M.
Webster, J. D.
Bailey, K. L.
Best, S.
DeLay, J.
Detrisac, C. J.
Fitzgerald, S. D.
Gamble, D.
Ginn, P. E.
Goldschmidt, M. H.
Hendrick, M. J.
Howerth, E. W.
Janovitz, E. B.
Langohr, I.
Lenz, S. D.
Lipscomb, T. P.
Miller, M. A.
Misdorp, W.
Moroff, S.
Mullaney, T. P.
Neyens, I.
O'Toole, D.
Ramos-Vara, J.
Scase, T. J.
Schulman, F. Y.
Sledge, D.
Smedley, R. C.
Smith, K.
Snyder, P. W.
Southorn, E.
Stedman, N. L.
Steficek, B. A.
Stromberg, P. C.
Valli, V. E.
Weisbrode, S. E.
Yager, J.
Heller, J.
Miller, R.
TI Proposal of a 2-Tier Histologic Grading System for Canine Cutaneous Mast
Cell Tumors to More Accurately Predict Biological Behavior
SO VETERINARY PATHOLOGY
LA English
DT Article
DE canine; histologic grading; mast cell tumor
ID MITOTIC INDEX; C-KIT; SURVIVAL; DOGS; PATHOLOGISTS; MORPHOMETRY;
PROGNOSIS
AB Currently, prognostic and therapeutic determinations for canine cutaneous mast cell tumors (MCTs) are primarily based on histologic grade. However, the use of different grading systems by veterinary pathologists and institutional modifications make the prognostic value of histologic grading highly questionable. To evaluate the consistency of microscopic grading among veterinary pathologists and the prognostic significance of the Patnaik grading system, 95 cutaneous MCTs from 95 dogs were graded in a blinded study by 28 veterinary pathologists from 16 institutions. Concordance among veterinary pathologists was 75% for the diagnosis of grade 3 MCTs and less than 64% for the diagnosis of grade 1 and 2 MCTs. To improve concordance among pathologists and to provide better prognostic significance, a 2-tier histologic grading system was devised. The diagnosis of high-grade MCTs is based on the presence of any one of the following criteria: at least 7 mitotic figures in 10 high-power fields (hpf); at least 3 multinucleated (3 or more nuclei) cells in 10 hpf; at least 3 bizarre nuclei in 10 hpf; karyomegaly (ie, nuclear diameters of at least 10% of neoplastic cells vary by at least two-fold). Fields with the highest mitotic activity or with the highest degree of anisokaryosis were selected to assess the different parameters. According to the novel grading system, high-grade MCTs were significantly associated with shorter time to metastasis or new tumor development, and with shorter survival time. The median survival time was less than 4 months for high-grade MCTs but more than 2 years for low-grade MCTs.
C1 [Kiupel, M.] Michigan State Univ, Dept Pathobiol & Diagnost Invest, Diagnost Ctr Populat & Anim Hlth, Coll Vet Med, Lansing, MI 48910 USA.
[Webster, J. D.] NCI, Mol Pathol Unit, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Bailey, K. L.] Amgen Inc, Seattle, WA USA.
[Best, S.; Southorn, E.; Yager, J.] Yager Best Histovet, Guelph, ON, Canada.
[DeLay, J.] Univ Guelph, Hlth Anim Lab, Guelph, ON N1G 2W1, Canada.
[Detrisac, C. J.] Pathol Associates Inc, Charles River Labs, Chicago, IL USA.
[Gamble, D.; Moroff, S.] Antech Diagnost, Lake Success, NY USA.
[Ginn, P. E.] Univ Florida, Coll Vet Med, Dept Infect Dis & Pathol, Gainesville, FL USA.
[Goldschmidt, M. H.; Hendrick, M. J.] Univ Penn, Sch Vet Med, Dept Pathobiol, Philadelphia, PA 19104 USA.
[Howerth, E. W.] Univ Georgia, Coll Vet Med, Dept Pathol, Athens, GA 30602 USA.
[Janovitz, E. B.] Bristol Myers Squibb Co, Dept Discovery Toxicol, Princeton, NJ USA.
[Lenz, S. D.; Snyder, P. W.] Purdue Univ, Sch Vet Med, Dept Comparat Pathobiol, W Lafayette, IN 47907 USA.
[Lipscomb, T. P.; Schulman, F. Y.] Armed Forces Inst Pathol, Dept Vet Pathol, Washington, DC 20306 USA.
[Misdorp, W.] Univ Utrecht, Fac Vet Med, Dept Pathobiol, Utrecht, Netherlands.
[Neyens, I.] Charles River Labs Preclin Serv Montreal Inc, Senneville, PQ, Canada.
[O'Toole, D.] Univ Wyoming, Dept Vet Sci, Wyoming State Vet Lab, Laramie, WY 82071 USA.
[Scase, T. J.] Bridge Pathol Ltd, Bristol, Avon, England.
[Smith, K.] Univ London, Royal Vet Coll, Dept Pathol & Infect Dis, N Mymms, Herts, England.
[Stedman, N. L.] Busch Gardens, Tampa, FL USA.
[Stromberg, P. C.; Weisbrode, S. E.] Ohio State Univ, Coll Vet Med, Dept Vet Biosci, Columbus, OH 43210 USA.
[Valli, V. E.] VDx Vet Diagnost, Davis, CA USA.
[Heller, J.] Charles Sturt Univ, Sch Anim & Vet Sci, Wagga Wagga, NSW, Australia.
[Miller, R.] Michigan State Univ, Coll Vet Med, Ctr Comparat Epidemiol, E Lansing, MI 48824 USA.
RP Kiupel, M (reprint author), Michigan State Univ, Dept Pathobiol & Diagnost Invest, Diagnost Ctr Populat & Anim Hlth, Coll Vet Med, 4125 Beaumont Rd,Room 152A, Lansing, MI 48910 USA.
EM kiupel@dcpah.msu.edu
RI Heller, Jane/H-9596-2016;
OI Heller, Jane/0000-0003-3993-0160; Langohr, Ingeborg/0000-0001-7366-4391;
Goldschmidt, Michael/0000-0001-9515-0535
FU initiative of the American College of Veterinary Pathologists' Oncology
Committee; World Small Animal Veterinary Association; College of
Veterinary Medicine, Michigan State University
FX We thank the clinical faculty who provided follow-up data on dogs. This
study represents an initiative of the American College of Veterinary
Pathologists' Oncology Committee; the manuscript was also reviewed and
endorsed by the World Small Animal Veterinary Association. We thank both
organizations for their support and guidance.; Funding for this study
was provided in part by the Companion Animal Fund of the College of
Veterinary Medicine, Michigan State University.
NR 19
TC 82
Z9 84
U1 9
U2 43
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0300-9858
J9 VET PATHOL
JI Vet. Pathol.
PD JAN
PY 2011
VL 48
IS 1
BP 147
EP 155
DI 10.1177/0300985810386469
PG 9
WC Pathology; Veterinary Sciences
SC Pathology; Veterinary Sciences
GA 719JH
UT WOS:000287200500012
PM 21062911
ER
PT J
AU Yoshii, K
Igarashi, M
Ito, K
Kariwa, H
Holbrook, MR
Takashima, I
AF Yoshii, Kentaro
Igarashi, Manabu
Ito, Kimihito
Kariwa, Hiroaki
Holbrook, Michael R.
Takashima, Ikuo
TI Construction of an infectious cDNA clone for Omsk hemorrhagic fever
virus, and characterization of mutations in NS2A and NS5
SO VIRUS RESEARCH
LA English
DT Article
DE Omsk hemorrhagic fever; Flavivirus; Infectious cDNA; Viral replication
ID BORNE-ENCEPHALITIS-VIRUS; WEST-NILE-VIRUS; DEPENDENT RNA-POLYMERASE;
NONSTRUCTURAL PROTEIN NS2A; DENGUE VIRUS; SECONDARY STRUCTURE;
CRYSTAL-STRUCTURE; FLAVIVIRUS; STRAIN; REPLICATION
AB Omsk hemorrhagic fever virus (OHFV) is a member of the tick-borne encephalitis serocomplex of flaviviruses, and causes hemorrhagic disease in humans. In this study, an infectious cDNA of OHFV was constructed to investigate the molecular mechanisms involved in OHFV pathogenesis for the first time. Our cDNA clone was capable of producing infectious virus which is genetically identical to the parental Guriev strain, and the recombinant virus showed similar biological properties to the parental virus including growth kinetics and virulence characteristics. While characterizing the cDNAs, fortuitous mutations at NS2A position 46 and NS5 position 836 were found to affect viral production. By using a viral replicon expressing luciferase, it was shown that both of the mutations produced a defect in RNA replication and that the NS5 mutation induced a temperature-sensitive phenotype, indicating the importance of these residues in RNA replication. This infectious cDNA will be a useful tool to study the replication and pathogenesis of OHFV. (C) 2010 Elsevier B.V. All rights reserved.
C1 [Yoshii, Kentaro] Hokkaido Univ, Publ Hlth Lab, Grad Sch Vet Med, Kita Ku, Sapporo, Hokkaido 0600818, Japan.
[Yoshii, Kentaro; Holbrook, Michael R.] Univ Texas Med Branch, Dept Pathol, Inst Human Infect & Immun, Galveston, TX 77555 USA.
[Igarashi, Manabu; Ito, Kimihito] Hokkaido Univ, Dept Global Epidemiol, Res Ctr Zoonosis Control, Sapporo, Hokkaido 0010020, Japan.
[Holbrook, Michael R.] NIAID Integrated Res Facil, Frederick, MD 21702 USA.
RP Yoshii, K (reprint author), Hokkaido Univ, Publ Hlth Lab, Grad Sch Vet Med, Kita Ku, Kita 18 Nishi 9, Sapporo, Hokkaido 0600818, Japan.
EM kyoshii@vetmed.hokudai.ac.jp
RI Kariwa, Hiroaki/A-5258-2012; Ito, Kimihito/E-9975-2012; Igarashi,
Manabu/F-6871-2012; YOSHII, Kentaro/A-4808-2012
OI Ito, Kimihito/0000-0003-4986-1795;
FU Japan Health Sciences Foundation; Ministry of Education, Science,
Sports, and Culture of Japan; Ministry of Health, Labour, and Welfare of
Japan; Western Regional Center of Excellence [U54 AI057156]
FX This work was supported by Overseas Assignment Program for Japanese
Researchers in Research into Emerging and Re-emerging Infectious
Diseases from The Japan Health Sciences Foundation and Grants-in-Aid for
Scientific Research from the Ministry of Education, Science, Sports, and
Culture of Japan, Health Sciences Grants for Research on Emerging and
Re-emerging Infectious Disease from the Ministry of Health, Labour, and
Welfare of Japan, and a Western Regional Center of Excellence (U54
AI057156) Career Development award (MRH) in part.
NR 55
TC 11
Z9 11
U1 1
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-1702
J9 VIRUS RES
JI Virus Res.
PD JAN
PY 2011
VL 155
IS 1
BP 61
EP 68
DI 10.1016/j.virusres.2010.08.023
PG 8
WC Virology
SC Virology
GA 716YV
UT WOS:000287010300009
PM 20817056
ER
PT J
AU Wright, ME
Abdelzaher, AM
Solo-Gabriele, HM
Elmir, S
Fleming, LE
AF Wright, M. E.
Abdelzaher, A. M.
Solo-Gabriele, H. M.
Elmir, S.
Fleming, L. E.
TI The inter-tidal zone is the pathway of input of enterococci to a
subtropical recreational marine beach
SO WATER SCIENCE AND TECHNOLOGY
LA English
DT Article
DE enterococci; inter-tidal zone; marine beach; recreational beach; water
quality indicators
ID FECAL INDICATOR BACTERIA; ESCHERICHIA-COLI; WATER-QUALITY;
LAKE-MICHIGAN; SAND; ENVIRONMENT; SEDIMENTS; POPULATIONS; PERSISTENCE;
CALIFORNIA
AB Efforts were made to evaluate the source of enterococci levels at a recreational beach. Four monitoring efforts were implemented which included tidal studies, hourly sampling, runoff sampling, and spatially intensive sediment sampling. Spatially intensive sediment sampling indicated that enterococci concentrations consistently decreased away from the inter-tidal zone, both seaward and landward. During dry conditions, the highest concentrations in the water were observed during high tide (71 +/- 48 CFU/100 mL) and lower concentrations were observed during low tide (4 +/- 3 CFU/100 mL). Runoff was characterised by very high levels (11,700 CFU/100 mL). Results from these monitoring efforts collectively showed that the source of enterococci to the study beach is geographically located within the inter-tidal zone. Wash-in from the inter-tidal zone through tidal action and runoff plays a major role in controlling enterococci levels within the water column. Such results are significant in identifying the source and transport mechanisms of enterococci, which can subsequently be used as part of a modelling effort aimed at predicting enterococci levels at recreational beaches.
C1 [Wright, M. E.; Abdelzaher, A. M.; Solo-Gabriele, H. M.; Elmir, S.; Fleming, L. E.] Univ Miami, NSF, NIEHS, Oceans & Human Hlth Ctr,Rosenstiel Sch Marine & A, Miami, FL 33149 USA.
[Wright, M. E.; Abdelzaher, A. M.; Solo-Gabriele, H. M.; Elmir, S.] Univ Miami, Dept Civil Architectural & Environm Engn, Coral Gables, FL 33124 USA.
[Elmir, S.] Miami Dade Cty Hlth Dept, Miami, FL 33056 USA.
[Fleming, L. E.] Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL 33136 USA.
RP Solo-Gabriele, HM (reprint author), Univ Miami, NSF, NIEHS, Oceans & Human Hlth Ctr,Rosenstiel Sch Marine & A, 4600 Rickenbacker Causeway,EG 211 Key Biscayne, Miami, FL 33149 USA.
EM hmsolo@miami.edu
FU NSF-NIEHS [NSF OCE0432368/0911373]; NIEHS [P50 ES12736-01]; NSF-REU [OCE
0432368]
FX This work was funded by NSF-NIEHS Oceans.and Human Health Program (NSF
OCE0432368/0911373 and NIEHS P50 ES12736-01) and the NSF-REU Program
(OCE 0432368). We would like to thank all the students, scientists and
professionals who assisted with sample collection.
NR 26
TC 27
Z9 27
U1 3
U2 14
PU IWA PUBLISHING
PI LONDON
PA ALLIANCE HOUSE, 12 CAXTON ST, LONDON SW1H0QS, ENGLAND
SN 0273-1223
J9 WATER SCI TECHNOL
JI Water Sci. Technol.
PY 2011
VL 63
IS 3
BP 542
EP 549
DI 10.2166/wst.2011.255
PG 8
WC Engineering, Environmental; Environmental Sciences; Water Resources
SC Engineering; Environmental Sciences & Ecology; Water Resources
GA 719DY
UT WOS:000287181200023
PM 21278478
ER
PT S
AU Izumi, C
Bird, J
Schachinger, T
Oliver, D
Iwasa, KH
AF Izumi, Chisako
Bird, Jonathan
Schaechinger, Torsten
Oliver, Dominik
Iwasa, Kuni H.
BE Shera, CA
Olson, ES
TI The Evolution of Prestin: Examination with Membrane Thickness
Sensitivity
SO WHAT FIRE IS IN MINE EARS: PROGRESS IN AUDITORY BIOMECHANICS:
PROCEEDINGS OF THE 11TH INTERNATIONAL MECHANICS OF HEARING WORKSHOP
SE AIP Conference Proceedings
LA English
DT Proceedings Paper
CT 11th International Workshop on the Mechanics of Hearing
CY JUL 16-22, 2011
CL Williams Coll, Williamstown, MA
HO Williams Coll
DE evolution; membrane thickness; hydrophobic mismatch
ID PROTEIN
AB Prestin (SLC26A5) is a membrane protein that is essential for electromotility of outer hair cells and, in turn, for the cochlear amplifier. This function is mammalian innovation and prestin orthologs in non-mammalian hair cells function as anion exchangers rather than a motile element. Taking advantage of this evolutionary change, we found that the sensitivity of prestin orthologs to membrane thickness is inversely related to their effectiveness for the motile function. In addition, a chimera between zebrafish prestin and rat prestin, which shows motile functionality, has membrane thickness sensitivity lower than any prestin ortholog we have examined, confirming the relationship.
C1 [Izumi, Chisako; Bird, Jonathan; Iwasa, Kuni H.] NIDCD, NIH, Bethesda, MD 20892 USA.
[Izumi, Chisako] Hamamatsu Med Univ, Dept Otolaryngol, Hamamatsu, Shizuoka, Japan.
[Schaechinger, Torsten] Univ Freiburg, Dept Phys, Freiburg, Germany.
[Oliver, Dominik] Univ Marburg, Dept Physiol, Marburg, Germany.
RP Izumi, C (reprint author), NIDCD, NIH, Bethesda, MD 20892 USA.
OI Iwasa, Kuni/0000-0002-9397-7704
NR 4
TC 0
Z9 0
U1 0
U2 0
PU AMER INST PHYSICS
PI MELVILLE
PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA
SN 0094-243X
BN 978-0-7354-0975-0
J9 AIP CONF PROC
PY 2011
VL 1403
DI 10.1063/1.3658079
PG 2
WC Audiology & Speech-Language Pathology; Physics, Applied
SC Audiology & Speech-Language Pathology; Physics
GA BZL60
UT WOS:000301945200028
ER
PT J
AU Barbey, AK
Grafman, J
AF Barbey, Aron K.
Grafman, Jordan
TI An integrative cognitive neuroscience theory of social reasoning and
moral judgment
SO WILEY INTERDISCIPLINARY REVIEWS-COGNITIVE SCIENCE
LA English
DT Article
ID MEDIAL PREFRONTAL CORTEX; WASON SELECTION TASK; NEURAL BASIS;
INDIVIDUAL-DIFFERENCES; EVENT KNOWLEDGE; EXCHANGE; DAMAGE; FMRI;
PERSPECTIVE; EVOLUTION
AB Cognitive neuroscience has made considerable progress in understanding the involvement of the prefrontal cortex (PFC) in social cognition and moral judgment. Accumulating evidence suggests that representations within the lateral PFC enable people to orchestrate their thoughts and actions in concert with their intentions to support goal-directed social behavior. Despite the pivotal role of this region in guiding social interactions, remarkably little is known about the functional organization and forms of social knowledge mediated by the lateral PFC. Here, we review recent theoretical developments in evolutionary psychology and emerging evidence from the social and decision neuroscience literatures demonstrating the importance of the lateral PFC for orchestrating behavior on the basis of evolutionarily adaptive social norms for obligatory, prohibited, and permissible courses of action. (C) 2010 John Wiley& Sons, Ltd. WIREs Cogn Sci 2011 2 55-67 DOI: 10.1002/wcs.84
C1 [Barbey, Aron K.; Grafman, Jordan] NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA.
[Barbey, Aron K.] Georgetown Univ, Dept Psychol, Washington, DC 20057 USA.
RP Grafman, J (reprint author), NINDS, Cognit Neurosci Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM grafmanj@ninds.nih.gov
RI Barbey, Aron/L-7312-2015;
OI Barbey, Aron/0000-0002-6092-0912; Grafman, Jordan H./0000-0001-8645-4457
NR 106
TC 3
Z9 3
U1 2
U2 22
PU WILEY PERIODICALS, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA
SN 1939-5078
J9 WIRES COGN SCI
JI Wiley Interdiscip. Rev.-Cogn. Sci.
PD JAN-FEB
PY 2011
VL 2
IS 1
BP 55
EP 67
DI 10.1002/wcs.84
PG 13
WC Psychology, Experimental
SC Psychology
GA 863OL
UT WOS:000298174800006
PM 26301913
ER
PT J
AU Tandon, P
Nordstrom, RJ
AF Tandon, Pushpa
Nordstrom, Robert J.
TI Next-generation imaging development for nanoparticle biodistribution
measurements
SO WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY
LA English
DT Review
ID MAGNETIC-RESONANCE; CONTRAST AGENT; END-POINT; FLUORESCENCE; MELANOMA;
TRIALS; MRI
AB As nanotechnologies move closer to use in humans, quantitative imaging methods will play a vital role in answering questions of biodistribution. Accurate knowledge of the location and quantity of in vivo nanoconstructs and carriers is a challenging task, and newmethods of quantitative imaging at appropriate resolutions are being developed and tested. Sustaining simultaneous advancement in both imaging development and nanotechnology research requires multidisciplinary research teams conducting experiments with interconnected goals. On an even greater scale, networks of multidisciplinary teams focused on similar issues of imaging and probe development offer opportunities for leveraging resources, as well as providing a forum for sharing ideas and creating consensus on solutions to common challenges. The Network for Translational Research ( NTR): Optical Imaging in Multimodal Platforms from the National Cancer Institute is just such a network. Four multidisciplinary centers are accepting the challenges of developing and optimizing multimodal imaging hardware and software along with imaging probe development. These efforts are similar to the efforts that will be required for future studies of in vivo nanoparticle biodistribution. In addition to technology development and optimization, the network is organized to confront the challenges of validation of the imaging hardware and associated imaging agents, similar to the methods needed for validating nanomedicine. (C) 2010 John Wiley & Sons, Inc. WIREs Nanomed Nanobiotechnol 2011 3 5-10 DOI: 10.1002/wnan.117
C1 [Tandon, Pushpa; Nordstrom, Robert J.] NCI, NIH, Canc Imaging Program, Bethesda, MD 20892 USA.
RP Tandon, P (reprint author), NCI, NIH, Canc Imaging Program, Bethesda, MD 20892 USA.
EM tandonp@mail.nih.gov
NR 19
TC 5
Z9 5
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1939-5116
EI 1939-0041
J9 WIRES NANOMED NANOBI
JI Wiley Interdiscip. Rev.-Nanomed. Nanobiotechnol.
PD JAN-FEB
PY 2011
VL 3
IS 1
BP 5
EP 10
DI 10.1002/wnan.117
PG 6
WC Nanoscience & Nanotechnology; Medicine, Research & Experimental
SC Science & Technology - Other Topics; Research & Experimental Medicine
GA 701BQ
UT WOS:000285789700002
PM 20842710
ER
PT S
AU Kovalchuk, I
Nasibulina, A
Reed, BM
AF Kovalchuk, I.
Nasibulina, A.
Reed, B. M.
BE Hummer, KE
TI In Vitro Cold-Storage Duration of Cherry Shoots Is Affected by Carbon
Source and Nitrogen Concentration
SO XXVIII INTERNATIONAL HORTICULTURAL CONGRESS ON SCIENCE AND HORTICULTURE
FOR PEOPLE (IHC2010): III INTERNATIONAL SYMPOSIUM ON PLANT GENETIC
RESOURCES
SE Acta Horticulturae
LA English
DT Proceedings Paper
CT 28th International Horticultural Congress on Science and Horticulture
for People/3rd International Symposium on Plant Genetic Resources
CY AUG 22-27, 2010
CL Lisbon, PORTUGAL
DE germplasm storage; in vitro storage; micropropagation; Prunus
ID GERMPLASM; CULTURES; SURVIVAL; INVITRO; GROWTH
AB In vitro cold storage of fruit crop germplasm is useful for preservation of heritage or commercial cultivars. Shoot cultures of sour cherry (Prunus cerasus L.) cultivars 'Dolgozdannaya', 'Moya Radost' and 'Zukovskaya', were cold stored at 4 degrees C in either five-section tissue-culture bags or in 150-ml glass jars. Carbon sources (3% sucrose, 2 or 3% mannitol, or 2% sucrose + 2% mannitol) were tested in Murashige and Skoog (MS) medium with or without plant growth regulators (PGRs). Nitrate nitrogen at 100, 50 or 25% of the normal MS concentration was also tested. In some treatments, shoot cultures of the three cherry cultivars stored at 4 degrees C remained viable for over 30 months. A significant variation in the storage duration and significant interactions of the cultivar, treatment, and container were observed. Sucrose was the best carbon source for all three genotypes and allowed storage for more than 30 months. Shoots stored on 2 or 3% mannitol survived only 6 to 12 months while the combination of 2% mannitol and 2% sucrose extended storage to 30 months. The addition of abscisic acid to 3% sucrose MS medium significantly decreased storage duration. 57 accessions of sour cherry germplasm were stored in tissue culture bags on 3% sucrose MS medium without PGRs and remained in good condition for 13 to 30 months. Currently, 68 P. cerasus germplasm accessions of the Kazakhstan National Cherry Collection are stored in tissue-culture bags with MS medium, PGRs, and 3% sucrose.
C1 [Kovalchuk, I.; Nasibulina, A.] Natl Biotechnol Ctr, Inst Plant Biol & Biotechnol, Timiryazev Str 45, Alma Ata 050040, Kazakhstan.
[Reed, B. M.] United States Dept Agr, Natl Clonal Germplasm Repository, Agr Res Serv, Corvallis, OR 97333 USA.
RP Kovalchuk, I (reprint author), Natl Biotechnol Ctr, Inst Plant Biol & Biotechnol, Timiryazev Str 45, Alma Ata 050040, Kazakhstan.
EM kovalchuk_i_u@mail.ru; Barbara.Reed@ars.usda.gov
OI Reed, Barbara/0000-0003-0079-8473
FU International Science and Technology Center [K428]; US Department of
Agriculture; Agricultural Research Service CRIS [5358- 21000- 033D]
FX This project was supported by funds from the International Science and
Technology Center Grant K428 and the US Department of Agriculture,
Agricultural Research Service CRIS project 5358- 21000- 033D.
NR 18
TC 2
Z9 2
U1 1
U2 4
PU INT SOC HORTICULTURAL SCIENCE
PI LEUVEN 1
PA PO BOX 500, 3001 LEUVEN 1, BELGIUM
SN 0567-7572
BN 978-90-66055-54-4
J9 ACTA HORTIC
PY 2011
VL 918
BP 167
EP 175
PG 9
WC Horticulture
SC Agriculture
GA BDH95
UT WOS:000313331500020
ER
PT J
AU Boekhout, T
Fonseca, A
Sampaio, JP
Bandoni, RJ
Fell, JW
Kwon-Chung, KJ
AF Boekhout, Teun
Fonseca, Alvaro
Sampaio, Jose Paulo
Bandoni, Robert J.
Fell, Jack W.
Kwon-Chung, Kyung J.
BE Kurtzman, CP
Fell, JW
Boekhout, T
TI Discussion of Teleomorphic and Anamorphic Basidiomycetous Yeasts
SO YEASTS: A TAXONOMIC STUDY, VOLS 1-3, 5TH EDITION
LA English
DT Article; Book Chapter
C1 [Boekhout, Teun] CBS KNAW Fungal Biodivers Ctr, NL-3584 CT Utrecht, Netherlands.
[Bandoni, Robert J.] Univ British Columbia, Dept Bot, Vancouver, BC V6T 1Z4, Canada.
[Fell, Jack W.] Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, Key Biscayne, FL 33149 USA.
[Fonseca, Alvaro; Sampaio, Jose Paulo] Univ Nova Lisboa, Ctr Recursos Microbiol CREM, Dept Ciencias Vida, Fac Ciencias & Tecnol, P-2829516 Caparica, Portugal.
[Kwon-Chung, Kyung J.] NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Boekhout, T (reprint author), CBS KNAW Fungal Biodivers Ctr, Uppsalalaan 8, NL-3584 CT Utrecht, Netherlands.
RI Fonseca, Alvaro/C-5544-2011;
OI Fonseca, Alvaro/0000-0001-9785-9433; Sampaio, Jose/0000-0001-8145-5274
NR 0
TC 32
Z9 33
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
BN 978-0-123-84868-0
PY 2011
BP 1339
EP 1372
DI 10.1016/B978-0-444-52149-1.00100-2
PG 34
WC Mycology
SC Mycology
GA BCV60
UT WOS:000311576700101
ER
PT J
AU Kwon-Chung, KJ
AF Kwon-Chung, Kyung J.
BE Kurtzman, CP
Fell, JW
Boekhout, T
TI Chionosphaera Cox (1976)
SO YEASTS: A TAXONOMIC STUDY, VOLS 1-3, 5TH EDITION
LA English
DT Article; Book Chapter
C1 NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Kwon-Chung, KJ (reprint author), NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
BN 978-0-123-84868-0
PY 2011
BP 1395
EP 1401
DI 10.1016/B978-0-444-52149-1.00106-3
PG 7
WC Mycology
SC Mycology
GA BCV60
UT WOS:000311576700107
ER
PT J
AU Kwon-Chung, KJ
AF Kwon-Chung, Kyung J.
BE Kurtzman, CP
Fell, JW
Boekhout, T
TI Filobasidiella Kwon-Chung (1975)
SO YEASTS: A TAXONOMIC STUDY, VOLS 1-3, 5TH EDITION
LA English
DT Article; Book Chapter
C1 NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Kwon-Chung, KJ (reprint author), NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
NR 0
TC 5
Z9 5
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
BN 978-0-123-84868-0
PY 2011
BP 1443
EP 1455
DI 10.1016/B978-0-444-52149-1.00114-2
PG 13
WC Mycology
SC Mycology
GA BCV60
UT WOS:000311576700115
ER
PT J
AU Kwon-Chung, KJ
AF Kwon-Chung, Kyung J.
BE Kurtzman, CP
Fell, JW
Boekhout, T
TI Filobasidium Olive (1968)
SO YEASTS: A TAXONOMIC STUDY, VOLS 1-3, 5TH EDITION
LA English
DT Article; Book Chapter
C1 NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Kwon-Chung, KJ (reprint author), NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
NR 0
TC 3
Z9 3
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
BN 978-0-123-84868-0
PY 2011
BP 1457
EP 1465
DI 10.1016/B978-0-444-52149-1.00115-4
PG 9
WC Mycology
SC Mycology
GA BCV60
UT WOS:000311576700116
ER
PT S
AU Butler, MG
Gore, AV
Weinstein, BM
AF Butler, Matthew G.
Gore, Aniket V.
Weinstein, Brant M.
BE Detrich, HW
Westerfield, M
Zon, LI
TI Zebrafish as a Model for Hemorrhagic Stroke
SO ZEBRAFISH: DISEASE MODELS AND CHEMICAL SCREENS, 3RD EDITION
SE Methods in Cell Biology
LA English
DT Review; Book Chapter
ID CEREBRAL CAVERNOUS MALFORMATIONS; VASCULAR ENDOTHELIAL CADHERIN;
BLOOD-BRAIN-BARRIER; ZINC-FINGER PROTEIN; IN-FRAME DELETION;
VE-CADHERIN; CELL-JUNCTIONS; TIGHT JUNCTION; TYROSINE PHOSPHORYLATION;
MOLECULAR-ORGANIZATION
AB Blood vessels perform the fundamental role of providing conduits for the circulation of oxygen and nutrients and the removal of waste products throughout the body. Disruption of tissue perfusion by ischemia or hemorrhage of blood vessels has a range of devastating consequences including stroke. Stroke is a complex trait that includes both genetic and environmental risk factors. The zebrafish is an attractive model for the study of hemorrhagic stroke due to the conservation of the molecular mechanisms of blood vascular development among vertebrates and the experimental advantages that can be applied to zebrafish embryos and larva. This chapter will focus on the maintenance of vascular integrity and some of the seminal experimentation carried out in the zebrafish.
C1 [Butler, Matthew G.; Gore, Aniket V.; Weinstein, Brant M.] Natl Inst Child Hlth & Dev, Program Genom Differentiat, NIH, Bethesda, MD USA.
RP Butler, MG (reprint author), Natl Inst Child Hlth & Dev, Program Genom Differentiat, NIH, Bethesda, MD USA.
NR 105
TC 4
Z9 4
U1 1
U2 5
PU ELSEVIER ACADEMIC PRESS INC
PI SAN DIEGO
PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0091-679X
BN 978-0-12-381320-6
J9 METHOD CELL BIOL
JI Methods Cell Biol.
PY 2011
VL 105
BP 137
EP 161
DI 10.1016/B978-0-12-381320-6.00006-0
PG 25
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA BXA72
UT WOS:000295550300006
PM 21951529
ER
PT S
AU Amsterdam, A
Varshney, GK
Burgess, SM
AF Amsterdam, Adam
Varshney, Gaurav Kumar
Burgess, Shawn Michael
BE Detrich, HW
Westerfield, M
Zon, LI
TI Retroviral-mediated Insertional Mutagenesis in Zebrafish
SO ZEBRAFISH: GENETICS, GENOMICS AND INFORMATICS, 3RD EDITION
SE Methods in Cell Biology
LA English
DT Review; Book Chapter
ID SLEEPING-BEAUTY TRANSPOSON; GERM-LINE TRANSMISSION; VESICULAR
STOMATITIS-VIRUS; DROSOPHILA GENOME; DANIO-RERIO; PROVIRAL INSERTIONS;
TUMOR-SUPPRESSOR; FACTOR-I; GENE; INTEGRATION
AB Since the initial publication of this chapter in 2004, additional methodologies have been developed which could improve and/or complement the original retroviral-mediated insertional mutagenesis. Retroviral vectors have also been shown to be useful for goals other than mutagenesis. In addition, retroviral-mediated insertional mutagenesis has been applied to zebrafish for use in reverse genetics as well as forward screening. Finally, the insertional mutant collection described herein has been screened by a number of labs to find a host of mutants (with genes already identified) with developmental and/or growth defects affecting the eye, liver, skin, craniofacial skeleton, kidney, myeloid cells, hematopoietic stem cells, and axon pathfinding, as well as mutants with defects in the cell cycle or DNA damage response, altered aging properties, and modulated cardiac repolarization. The major complementary approaches and new uses of this technique include:
Pseudotyped retroviruses have been used to deliver enhancer trap vectors, which allows selection of insertions in or near genes with particular expression patterns. Although the mutagenicity of these vectors has yet to be determined, they are useful purely because they generate a large number of transgenic lines with visible reporters (e.g., Green Fluorescent Protein GFP) expressed in interesting patterns and they provide information regarding gene regulation in the context of genomic organization.
Gain-of-function vectors have been designed to allow for dominant genetic screens. Thus, genes whose overexpression results in phenotypes of interest can be efficiently identified.
Retroviruses can be used to make a library of insertions in which hundreds of thousands of mapped insertions can be recovered from frozen sperm samples. Such libraries could serve as on-the-shelf reverse genetic resources, whereby one can obtain a mutation in nearly any gene by simply recovering an insertion in that gene from the frozen sperm, similar to the use of gene-trap insertions and genome-wide gene targeting in ES cells in the mouse.
Transposons have been shown to be nearly as effective transgenesis vectors as retroviruses and thus may be used in similar screens - both for mutagenicity and gene traps and enhancer traps. It is possible that retroviruses and transposons could have different insertion site biases, making them important complementary technologies for genome-wide screening.
C1 [Amsterdam, Adam] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
[Varshney, Gaurav Kumar; Burgess, Shawn Michael] NHGRI, Bethesda, MD 20892 USA.
RP Amsterdam, A (reprint author), MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
RI Varshney, Gaurav/L-5261-2014;
OI Burgess, Shawn/0000-0003-1147-0596; Varshney, Gaurav
K./0000-0002-0429-1904
FU Intramural NIH HHS [ZIA HG000183-11]
NR 63
TC 11
Z9 11
U1 0
U2 6
PU ELSEVIER ACADEMIC PRESS INC
PI SAN DIEGO
PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0091-679X
BN 978-0-12-374814-0
J9 METHOD CELL BIOL
JI Methods Cell Biol.
PY 2011
VL 104
SI 3
BP 59
EP 82
DI 10.1016/B978-0-12-374814-0.00004-5
PG 24
WC Cell Biology
SC Cell Biology
GA BXA74
UT WOS:000295551800004
PM 21924157
ER
PT S
AU Liang, J
Renaud, G
Burgess, SM
AF Liang, Jin
Renaud, Gabriel
Burgess, Shawn M.
BE Detrich, HW
Westerfield, M
Zon, LI
TI Sequencing-based Expression Profiling in Zebrafish
SO ZEBRAFISH: GENETICS, GENOMICS AND INFORMATICS, 3RD EDITION
SE Methods in Cell Biology
LA English
DT Review; Book Chapter
ID GENE-EXPRESSION; RNA-SEQ; SERIAL ANALYSIS; HUMAN GENOME; TRANSCRIPTOME;
MICROARRAY; ACCURATE; REVEALS; TAGS
AB Gene expression profiling is a powerful technique for studying biological processes, especially tissue/organ-specific ones, at the molecular level. With the rapid development of the next-generation sequencing techniques, high throughput sequencing-based expression profiling techniques have been more and more widely adopted in molecular biology studies. In this chapter, we described a protocol for applying one of the sequencing-based expression profiling techniques, Digital Gene Expression (DGE), for zebrafish research. The protocol provides guidelines for wet-bench experimental procedures as well as for bioinformatics data analyses. We also discuss potential issues/challenges with the use of DGE.
C1 [Liang, Jin; Renaud, Gabriel; Burgess, Shawn M.] NHGRI, Bethesda, MD 20892 USA.
RP Liang, J (reprint author), NHGRI, Bethesda, MD 20892 USA.
OI Burgess, Shawn/0000-0003-1147-0596
FU Intramural NIH HHS [ZIA HG000183-11]
NR 32
TC 0
Z9 0
U1 1
U2 5
PU ELSEVIER ACADEMIC PRESS INC
PI SAN DIEGO
PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0091-679X
BN 978-0-12-374814-0
J9 METHOD CELL BIOL
JI Methods Cell Biol.
PY 2011
VL 104
SI 3
BP 379
EP 399
DI 10.1016/B978-0-12-374814-0.00021-5
PG 21
WC Cell Biology
SC Cell Biology
GA BXA74
UT WOS:000295551800021
PM 21924174
ER
PT S
AU Fero, K
Yokogawa, T
Burgess, HA
AF Fero, Kandice
Yokogawa, Tohei
Burgess, Harold A.
BE Kalueff, AV
Cachat, JM
TI The Behavioral Repertoire of Larval Zebrafish
SO ZEBRAFISH MODELS IN NEUROBEHAVIORAL RESEARCH
SE Neuromethods
LA English
DT Article; Book Chapter
DE Developing zebrafish; larvae; acoustic/vibrational stimuli; vestibular
stimuli; lateral line stimuli; visual stimuli; chemical stimuli;
locomotion; sensory cues; environmental adaptation; stereotypic
behavior; neuroanatomy; neuronal pathways; motor control; sensory
processing
ID PONTINE RETICULAR-FORMATION; DANIO-RERIO; LATERAL-LINE;
BRACHYDANIO-RERIO; STARTLE RESPONSE; OPTOKINETIC NYSTAGMUS; PREY
CAPTURE; CIRCADIAN RHYTHMICITY; PREPULSE INHIBITION; EMBRYONIC ZEBRAFISH
AB Shortly after larval zebrafish become free swimming their behavior is modulated by both autochthonous signals and external stimuli Larvae show rapid responses to a range of sensory cues but are also capable of executing extended behavioral programs in response to changes in the environment At this early stage, larvae have a small repertoire of discrete stereotyped movements which are deployed in different contexts to generate appropriate behavior We outline the range of behaviors defined in zebrafish larva to date and discuss insights into neural function revealed by behavioral assays A growing body of work demonstrates that tractability of behavior and neural connectivity in larval zebrafish facilitate the analysis of neural pathways underlying vertebrate motor control and sensory processing
C1 [Fero, Kandice; Yokogawa, Tohei; Burgess, Harold A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Genet Lab, NIH, Bethesda, MD USA.
RP Fero, K (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Genet Lab, NIH, Bethesda, MD USA.
RI Burgess, Harold/B-8474-2015
OI Burgess, Harold/0000-0003-1966-7801
NR 204
TC 27
Z9 28
U1 0
U2 16
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA
SN 0893-2336
BN 978-1-60761-921-5
J9 NEUROMETHODS
JI Neuromethods
PY 2011
VL 52
BP 249
EP 291
DI 10.1007/978.1.60761.922.2_12
D2 10.1007/978-1-60761-922-2
PG 43
WC Cell Biology; Neurosciences
SC Cell Biology; Neurosciences & Neurology
GA BSA48
UT WOS:000284030800012
ER
PT J
AU Brady, RO
AF Brady, Roscoe O.
TI Benefits from Unearthing "a Biochemical Rosetta Stone"
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Editorial Material
ID INHERITED ENZYME DEFICIENCY; NIEMANN-PICK DISEASE;
GLUCOCEREBROSIDE-CLEAVING ENZYME; IN-UTERO DIAGNOSIS; GAUCHERS-DISEASE;
REPLACEMENT THERAPY; FABRYS-DISEASE; PURIFIED GLUCOCEREBROSIDASE; FATTY
ACIDS; METABOLISM
C1 NINDS, NIH, Bethesda, MD 20892 USA.
RP Brady, RO (reprint author), NINDS, NIH, Bethesda, MD 20892 USA.
EM bradyr@ninds.nih.gov
NR 46
TC 7
Z9 7
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 DEC 31
PY 2010
VL 285
IS 53
BP 41216
EP 41221
DI 10.1074/jbc.X110.197954
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 698VV
UT WOS:000285622600007
PM 21030589
ER
PT J
AU Walseng, E
Furuta, K
Goldszmid, RS
Weih, KA
Sher, A
Roche, PA
AF Walseng, Even
Furuta, Kazuyuki
Goldszmid, Romina S.
Weih, Karis A.
Sher, Alan
Roche, Paul A.
TI Dendritic Cell Activation Prevents MHC Class II Ubiquitination and
Promotes MHC Class II Survival Regardless of the Activation Stimulus
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID TOXOPLASMA-GONDII; PLASMA-MEMBRANE; COMPLEXES; SURFACE; EXPRESSION;
MATURATION; INFECTION; TRANSPORT; PARASITES; FUSION
AB The expression of MHC class II (MHC-II) on the surface of antigen-presenting cells, such as dendritic cells (DCs), is tightly regulated during cellular activation. Many cells, including DCs, are activated following stimulation of innate Toll-like receptors (TLRs) by products of microorganisms. In the resting (immature) state, MHC-II is ubiquitinated in immature DCs and is rapidly degraded; however, after activation of these cells with MyD88-dependent TLR ligands, MHC-II ubiquitination is blocked, and MHC-II survival is prolonged. We now show that DC activation using MyD88-dependent TLR ligands, MyD88-independent TLR ligands, and even infection with the intracellular parasite Toxoplasma gondii leads to identical changes in MHC-II expression, ubiquitination, and surface stability, revealing a conserved role for enhanced MHC-II stability after DC activation by different stimuli.
C1 [Walseng, Even; Furuta, Kazuyuki; Weih, Karis A.; Roche, Paul A.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Goldszmid, Romina S.; Sher, Alan] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Goldszmid, Romina S.] NCI, Expt Immunol Lab, Canc & Inflammat Program, Ctr Canc Res,NIH, Frederick, MD 21702 USA.
RP Roche, PA (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10,Rm 4B36, Bethesda, MD 20892 USA.
EM paul.roche@nih.gov
FU National Institutes of Health of NCI and NIAID
FX This work was supported, in whole or in part, by the National Institutes
of Health Intramural Research Programs of NCI and NIAID.
NR 23
TC 23
Z9 23
U1 0
U2 1
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD DEC 31
PY 2010
VL 285
IS 53
BP 41749
EP 41754
DI 10.1074/jbc.M110.157586
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 698VV
UT WOS:000285622600062
PM 21047782
ER
PT J
AU Legiewicz, M
Zolotukhin, AS
Pilkington, GR
Purzycka, KJ
Mitchell, M
Uranishi, H
Bear, J
Pavlakis, GN
Le Grice, SFJ
Felber, BK
AF Legiewicz, Michal
Zolotukhin, Andrei S.
Pilkington, Guy R.
Purzycka, Katarzyna J.
Mitchell, Michelle
Uranishi, Hiroaki
Bear, Jenifer
Pavlakis, George N.
Le Grice, Stuart F. J.
Felber, Barbara K.
TI The RNA Transport Element of the Murine musD Retrotransposon Requires
Long-range Intramolecular Interactions for Function
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; KISSING-LOOP INTERACTION; SELECTIVE
2'-HYDROXYL ACYLATION; SINGLE NUCLEOTIDE RESOLUTION; PRIMER EXTENSION
SHAPE; REV RESPONSE ELEMENT; VIRAL MESSENGER-RNA; SECONDARY STRUCTURE;
NUCLEAR EXPORT; MUTATIONAL ANALYSIS
AB Retrovirus replication requires specialized transport mechanisms to export genomic mRNA from the nucleus to the cytoplasm of the infected cell. This regulation is mediated by a combination of viral and/or cellular factors that interact with cis-acting RNA export elements linking the viral RNA to the cellular CRM1 or NXF1 nuclear export pathways. Endogenous type D murine LTR retrotransposons (musD) were reported to contain an RNA export element located upstream of the 3'-LTR. Although functionally equivalent, the musD export element, termed the musD transport element, is distinct from the other retroviral RNA export elements, such as the constitutive transport element of simian/Mason-Pfizer monkey retroviruses and the RNA transport element found in rodent intracisternal A-particle LTR retrotransposons. We demonstrate here that the minimal RNA transport element (musD transport element) of musD comprises multiple secondary structure elements that presumably serve as recognition signals for the cellular export machinery. We identified two classes of tertiary interactions, namely kissing loops and a pseudoknot. This work constitutes the first example of an RNA transport element requiring such structural motifs to mediate nuclear export.
C1 [Le Grice, Stuart F. J.] NCI, RT Biochem Sect, HIV Drug Resistance Program, Vaccine Branch,Ctr Canc Res,NIH, Frederick, MD 21702 USA.
[Zolotukhin, Andrei S.; Pilkington, Guy R.; Bear, Jenifer; Felber, Barbara K.] NCI, Human Retrovirus Pathogenesis Sect, NIH, Frederick, MD 21702 USA.
[Uranishi, Hiroaki; Pavlakis, George N.] NCI, Human Retrovirus Sect, Vaccine Branch, Ctr Canc Res,NIH, Frederick, MD 21702 USA.
RP Le Grice, SFJ (reprint author), NCI, RT Biochem Sect, HIV Drug Resistance Program, Vaccine Branch,Ctr Canc Res,NIH, POB B,Bldg 535,Rm 206, Frederick, MD 21702 USA.
EM legrices@mail.nih.gov; felberb@mail.nih.gov
FU National Institutes of Health of the NCI Center for Cancer Research
FX This work was supported, in whole or in part, by the National Institutes
of Health Intramural Research Program of the NCI Center for Cancer
Research.
NR 49
TC 15
Z9 15
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 DEC 31
PY 2010
VL 285
IS 53
BP 42097
EP 42104
DI 10.1074/jbc.M110.182840
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 698VV
UT WOS:000285622600094
PM 20978285
ER
PT J
AU Horvath, B
Lenzser, G
Benyo, B
Nemeth, T
Benko, R
Iring, A
Herman, P
Komjati, K
Lacza, Z
Sandor, P
Benyo, Z
AF Horvath, Bela
Lenzser, Gabor
Benyo, Balazs
Nemeth, Tamas
Benko, Rita
Iring, Andras
Herman, Peter
Komjati, Katalin
Lacza, Zsombor
Sandor, Peter
Benyo, Zoltan
TI Hypersensitivity to Thromboxane Receptor Mediated Cerebral Vasomotion
and CBF Oscillations during Acute NO-Deficiency in Rats
SO PLOS ONE
LA English
DT Article
ID DEPENDENT PROTEIN-KINASE; OXIDE SYNTHASE BLOCKADE; VASCULAR
SMOOTH-MUSCLE; NITRIC-OXIDE; BLOOD-FLOW; MYOSIN PHOSPHATASE;
LASER-DOPPLER; SUBARACHNOID HEMORRHAGE; PROSTAGLANDIN I-2; HYPERTENSIVE
RATS
AB Background: Low frequency (4-12 cpm) spontaneous fluctuations of the cerebrovascular tone (vasomotion) and oscillations of the cerebral blood flow (CBF) have been reported in diseases associated with endothelial dysfunction. Since endothelium-derived nitric oxide (NO) suppresses constitutively the release and vascular effects of thromboxane A(2) (TXA(2)), NO-deficiency is often associated with activation of thromboxane receptors (TP). In the present study we hypothesized that in the absence of NO, overactivation of the TP-receptor mediated cerebrovascular signaling pathway contributes to the development of vasomotion and CBF oscillations.
Methodology/Principal Findings: Effects of pharmacological modulation of TP-receptor activation and its downstream signaling pathway have been investigated on CBF oscillations (measured by laser-Doppler flowmetry in anesthetized rats) and vasomotion (measured by isometric tension recording in isolated rat middle cerebral arteries, MCAs) both under physiological conditions and after acute inhibition of NO synthesis. Administration of the TP-receptor agonist U-46619 (1 mu g/kg iv.) to control animals failed to induce any changes of the systemic or cerebral circulatory parameters. Inhibition of the NO synthesis by nitro-L-arginine methyl esther (L-NAME, 100 mg/kg iv.) resulted in increased mean arterial blood pressure and a decreased CBF accompanied by appearance of CBF-oscillations with a dominant frequency of 148+/-2 mHz. U-46619 significantly augmented the CBF-oscillations induced by L-NAME while inhibition of endogenous TXA(2) synthesis by ozagrel (10 mg/kg iv.) attenuated it. In isolated MCAs U-46619 in a concentration of 100 nM, which induced weak and stable contraction under physiological conditions, evoked sustained vasomotion in the absence of NO, which effect could be completely reversed by inhibition of Rho-kinase by 10 mu M Y-27632.
Conclusion/Significance: These results suggest that hypersensitivity of the TP-receptor - Rho-kinase signaling pathway contributes to the development of low frequency cerebral vasomotion which may propagate to vasospasm in pathophysiological states associated with NO-deficiency.
C1 [Horvath, Bela; Lenzser, Gabor; Nemeth, Tamas; Benko, Rita; Iring, Andras; Herman, Peter; Komjati, Katalin; Lacza, Zsombor; Sandor, Peter; Benyo, Zoltan] Semmelweis Univ, Inst Human Physiol & Clin Expt Res, Budapest, Hungary.
[Horvath, Bela] NIAAA, NIH, Bethesda, MD USA.
[Lenzser, Gabor] Univ Pecs, Dept Neurosurg, Pecs, Hungary.
[Benyo, Balazs] Budapest Univ Technol & Econ, Dept Control Engn & Informat Technol, H-1117 Budapest, Hungary.
[Herman, Peter] Yale Univ, Dept Diagnost Radiol, Magnet Resonance Res Ctr, New Haven, CT 06510 USA.
RP Horvath, B (reprint author), Semmelweis Univ, Inst Human Physiol & Clin Expt Res, Budapest, Hungary.
EM bela.horvath@nih.gov
RI Iring, Andras/F-7092-2010; Horvath, Bela/A-7368-2009; Benyo,
Balazs/H-6208-2012;
OI Benyo, Balazs/0000-0003-2770-9127; Benyo, Zoltan/0000-0001-6015-0359
FU EFSD) European Foundation for the Study of Diabetes/Servier; Hungarian
Scientific Research Fund (OTKA) [K 62375, K82066]; NKTH National Office
for Research and Technology [OMFB-00770/2009, ALAP1-01298/2009]; ESZCSM
Health Science Council (ETT) [427/2009]; Tarsadalmi Megujulas Operativ
Program (TAMOP) [4.2.2-08/1/KMR-2008-004, 4.2.1/B-09/1/KMR-2010-000];
NKTH-OTKA-EU [MB08-A 80238]
FX This study was supported by an (EFSD) European Foundation for the Study
of Diabetes/Servier grant as well as by grants from the The Hungarian
Scientific Research Fund (Hungarian abbreviation: OTKA) (K 62375,
K82066), NKTH National Office for Research and Technology
(OMFB-00770/2009, ALAP1-01298/2009), ESZCSM Health Science Council
(ETT)(427/2009) and Tarsadalmi Megujulas Operativ Program (TAMOP)
(4.2.2-08/1/KMR-2008-004, 4.2.1/B-09/1/KMR-2010-000). Dr. Horvath was
supported by an NKTH-OTKA-EU Fellowship (MB08-A 80238). The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 42
TC 6
Z9 7
U1 1
U2 9
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD DEC 31
PY 2010
VL 5
IS 12
AR e14477
DI 10.1371/journal.pone.0014477
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 701RA
UT WOS:000285838900006
PM 21217826
ER
PT J
AU Sabir, N
Riazuddin, SA
Kaul, H
Iqbal, F
Nasir, IA
Zafar, AU
Qazi, ZA
Butt, NH
Khan, SN
Husnain, T
Hejtmancik, JF
Riazuddin, S
AF Sabir, Namerah
Riazuddin, S. Amer
Kaul, Haiba
Iqbal, Farheena
Nasir, Idrees A.
Zafar, Ahmad U.
Qazi, Zaheeruddin A.
Butt, Nadeem H.
Khan, Shaheen N.
Husnain, Tayyab
Hejtmancik, J. Fielding
Riazuddin, Sheikh
TI Mapping of a novel locus associated with autosomal recessive congenital
cataract to chromosome 8p
SO MOLECULAR VISION
LA English
DT Article
ID PAKISTANI FAMILY; CHILDHOOD BLINDNESS; NONSENSE MUTATION; GENE; MAPS
AB Purpose: To identify the disease locus for autosomal recessive congenital cataracts in a consanguineous Pakistani family.
Methods: All affected individuals underwent a detailed ophthalmologic examination. Blood samples were collected and genomic DNA was extracted. A genome-wide scan was completed with fluorescently-labeled microsatellite markers on genomic DNA from affected and unaffected family members. Logarithms of odds (LOD) scores were calculated under a fully penetrant autosomal recessive model of inheritance.
Results: Ophthalmic examination suggested that affected individuals have bilateral cataracts. Linkage analysis localized the critical interval to chromosome 8p with LOD scores of 3.19, and 3.08 at theta=0, obtained with markers D8S549 and D8S550, respectively. Haplotype analyses refined the critical interval to 37.92 cM (16.28 Mb) region, flanked by markers, D8S277 proximally and D8S1734 distally.
Conclusions: Here, we report a new locus for autosomal recessive congenital cataract mapped to chromosome 8p in a consanguineous Pakistani family.
C1 [Sabir, Namerah; Riazuddin, S. Amer; Kaul, Haiba; Iqbal, Farheena; Nasir, Idrees A.; Zafar, Ahmad U.; Khan, Shaheen N.; Husnain, Tayyab; Riazuddin, Sheikh] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore 53700, Pakistan.
[Riazuddin, S. Amer] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA.
[Butt, Nadeem H.; Riazuddin, Sheikh] Univ Hlth Sci, Allama Iqbal Med Coll, Lahore, Pakistan.
[Qazi, Zaheeruddin A.] Layton Rahmatulla Benevolent Trust Hosp, Lahore, Pakistan.
[Hejtmancik, J. Fielding] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
RP Riazuddin, S (reprint author), Univ Punjab, Natl Ctr Excellence Mol Biol, 87 W Canal Bank Rd, Lahore 53700, Pakistan.
EM riaz@aimrc.org
RI Nasim Khan, Shaheen/F-2135-2015; Husnain, Tayyab/G-3805-2015
FU Higher Education Commission, Pakistan; Ministry of Science and
Technology Islamabad, Pakistan; National Academy of Sciences; U.S.
Department of State, Washington DC USA
FX The authors are thankful to all the family members for their
participation in this study. This study was supported, in part by Higher
Education Commission and Ministry of Science and Technology Islamabad,
Pakistan, and the National Academy of Sciences, and the U.S. Department
of State, Washington DC USA (Note: All findings and conclusions are
those of the authors and do not necessarily reflect the views of the
National Academy of Sciences and the U. S. Department of State).
NR 24
TC 5
Z9 5
U1 0
U2 0
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD DEC 30
PY 2010
VL 16
IS 312
BP 2911
EP 2915
PG 5
WC Biochemistry & Molecular Biology; Ophthalmology
SC Biochemistry & Molecular Biology; Ophthalmology
GA 707UN
UT WOS:000286314100001
PM 21203409
ER
PT J
AU Grant, RM
Lama, JR
Anderson, PL
McMahan, V
Liu, AY
Vargas, L
Goicochea, P
Casapia, M
Guanira-Carranza, JV
Ramirez-Cardich, ME
Montoya-Herrera, O
Fernandez, T
Veloso, VG
Buchbinder, SP
Chariyalertsak, S
Schechter, M
Bekker, LG
Mayer, KH
Kallas, EG
Amico, KR
Mulligan, K
Bushman, LR
Hance, RJ
Ganoza, C
Defechereux, P
Postle, B
Wang, FR
McConnell, JJ
Zheng, JH
Lee, J
Rooney, JF
Jaffe, HS
Martinez, AI
Burns, DN
Glidden, DV
AF Grant, Robert M.
Lama, Javier R.
Anderson, Peter L.
McMahan, Vanessa
Liu, Albert Y.
Vargas, Lorena
Goicochea, Pedro
Casapia, Martin
Guanira-Carranza, Juan Vicente
Ramirez-Cardich, Maria E.
Montoya-Herrera, Orlando
Fernandez, Telmo
Veloso, Valdilea G.
Buchbinder, Susan P.
Chariyalertsak, Suwat
Schechter, Mauro
Bekker, Linda-Gail
Mayer, Kenneth H.
Kallas, Esper Georges
Amico, K. Rivet
Mulligan, Kathleen
Bushman, Lane R.
Hance, Robert J.
Ganoza, Carmela
Defechereux, Patricia
Postle, Brian
Wang, Furong
McConnell, J. Jeff
Zheng, Jia-Hua
Lee, Jeanny
Rooney, James F.
Jaffe, Howard S.
Martinez, Ana I.
Burns, David N.
Glidden, David V.
CA iPrEx Study Team
TI Preexposure Chemoprophylaxis for HIV Prevention in Men Who Have Sex with
Men.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID NONOCCUPATIONAL POSTEXPOSURE PROPHYLAXIS; MALE CIRCUMCISION; LIMITED
KNOWLEDGE; HOMOSEXUAL-MEN; INFECTION; TRANSMISSION; RISK; TENOFOVIR;
MACAQUES; TRIAL
AB Background: Antiretroviral chemoprophylaxis before exposure is a promising approach for the prevention of human immunodeficiency virus (HIV) acquisition.
Methods: We randomly assigned 2499 HIV-seronegative men or transgender women who have sex with men to receive a combination of two oral antiretroviral drugs, emtricitabine and tenofovir disoproxil fumarate (FTC-TDF), or placebo once daily. All subjects received HIV testing, risk-reduction counseling, condoms, and management of sexually transmitted infections.
Results: The study subjects were followed for 3324 person-years (median, 1.2 years; maximum, 2.8 years). Of these subjects, 10 were found to have been infected with HIV at enrollment, and 100 became infected during follow-up (36 in the FTC-TDF group and 64 in the placebo group), indicating a 44% reduction in the incidence of HIV (95% confidence interval, 15 to 63; P=0.005). In the FTC-TDF group, the study drug was detected in 22 of 43 of seronegative subjects (51%) and in 3 of 34 HIV-infected subjects (9%) (P<0.001). Nausea was reported more frequently during the first 4 weeks in the FTC-TDF group than in the placebo group (P<0.001). The two groups had similar rates of serious adverse events (P=0.57).
Conclusions: Oral FTC-TDF provided protection against the acquisition of HIV infection among the subjects. Detectable blood levels strongly correlated with the prophylactic effect. (Funded by the National Institutes of Health and the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT00458393.)
N Engl J Med 2010;363:2587-99.
C1 [Liu, Albert Y.; Buchbinder, Susan P.] San Francisco Dept Publ Hlth, HIV Res Sect, San Francisco, CA USA.
[Lama, Javier R.; Vargas, Lorena] Invest Med Salud, Lima, Peru.
[Lama, Javier R.; Guanira-Carranza, Juan Vicente; Ramirez-Cardich, Maria E.; Ganoza, Carmela] Asociac Civil Impacta Salud & Educ, Lima, Peru.
[Casapia, Martin] Asociac Civil Selva Amazon, Iquitos, Peru.
[Anderson, Peter L.; Bushman, Lane R.; Zheng, Jia-Hua] Univ Colorado, Denver, CO 80202 USA.
[Montoya-Herrera, Orlando; Fernandez, Telmo] Fdn Ecuatoriana Equidad, Guayaquil, Ecuador.
[Veloso, Valdilea G.] Fundacao Oswaldo Cruz, Inst Pesquisa Clin Evandro Chagas, Rio De Janeiro, Brazil.
[Schechter, Mauro] Univ Fed Rio de Janeiro, Hosp Escola Sao Francisco de Assis, Projeto Praca Onze, Rio De Janeiro, Brazil.
[Mayer, Kenneth H.] Brown Univ, Providence, RI 02912 USA.
[Mayer, Kenneth H.] Fenway Hlth, Fenway Inst, Boston, MA USA.
[Kallas, Esper Georges] Univ Sao Paulo, Sch Med, Div Clin Immunol & Allergy, Sao Paulo, Brazil.
[Kallas, Esper Georges] Inst Invest Imunol, Sao Paulo, Brazil.
[Chariyalertsak, Suwat] Chiang Mai Univ, Res Inst Hlth Sci, Chiang Mai 50000, Thailand.
[Bekker, Linda-Gail] Univ Cape Town, Desmond Tutu HIV Ctr, ZA-7925 Cape Town, South Africa.
[Bekker, Linda-Gail] Univ Cape Town, Dept Med, ZA-7925 Cape Town, South Africa.
[Martinez, Ana I.; Burns, David N.] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA.
[Rooney, James F.; Jaffe, Howard S.] Gilead Sci Inc, Foster City, CA 94404 USA.
[Postle, Brian] DF Net Res, Seattle, WA USA.
[Amico, K. Rivet] Appl Hlth Res, Brighton, MI USA.
[Amico, K. Rivet] Univ Connecticut, Ctr Hlth Intervent & Prevent, Storrs, CT USA.
[Grant, Robert M.; McMahan, Vanessa; Goicochea, Pedro; Hance, Robert J.; Defechereux, Patricia; McConnell, J. Jeff; Lee, Jeanny] Univ Calif San Francisco, Gladstone Inst Virol & Immunol, San Francisco, CA 94158 USA.
RP Grant, RM (reprint author), Univ Calif San Francisco, J David Gladstone Inst, 1650 Owens St, San Francisco, CA 94158 USA.
EM robert.grant@ucsf.edu
RI Kallas, Esper/C-9539-2012; Goncalves Veloso, Valdilea/J-6189-2012;
Imunologia, Inct/I-2124-2013;
OI Guanira, Juan/0000-0002-2746-3086
FU Division of Acquired Immunodeficiency Syndrome (DAIDS), National
Institute of Allergy and Infectious Diseases, National Institutes of
Health [UO1 AI64002]; Bill and Melinda Gates Foundation; DAIDS [UO1
AI84735, AI062333]; National Institutes of Health [UL1 RR024131];
Gilead; Merck; Bristol-Myers Squibb
FX Supported by the Division of Acquired Immunodeficiency Syndrome (DAIDS),
National Institute of Allergy and Infectious Diseases, National
Institutes of Health, as a cooperative agreement (UO1 AI64002, to Dr.
Grant) and by the Bill and Melinda Gates Foundation. Study drugs were
donated by Gilead Sciences. The pharmacological studies were sponsored
by a cooperative agreement with DAIDS (UO1 AI84735, to Dr. Anderson).
Support for some specimen handling came from a grant from DAIDS (RO1
AI062333, to Dr. Grant) and by the J. David Gladstone Institutes. Some
infrastructure support at the University of California at San Francisco
was provided by a grant from the National Institutes of Health (UL1
RR024131).; Dr. Grant reports receiving support as an advisor to Siemens
(the manufacturer of TruGene HIV-1 Genotyping Kit); Dr. Mayer reports
receiving grant support from Gilead, Merck, and Bristol-Myers Squibb;
Dr. Kallas reports serving on a data and safety monitoring board for
Merck; Dr. Schechter reports receiving consulting fees and grants from
Gilead; Drs. Liu and Anderson report receiving donations of study drug
from Gilead for various PrEP projects; and Drs. Jaffe and Rooney report
being employees of Gilead Sciences and owning stock in the company. 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 33
TC 1530
Z9 1564
U1 16
U2 161
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 DEC 30
PY 2010
VL 363
IS 27
BP 2587
EP 2599
DI 10.1056/NEJMoa1011205
PG 13
WC Medicine, General & Internal
SC General & Internal Medicine
GA 700SD
UT WOS:000285763700004
PM 21091279
ER
PT J
AU Kuhns, DB
Alvord, WG
Heller, T
Feld, JJ
Pike, KM
Marciano, BE
Uzel, G
DeRavin, SS
Priel, DAL
Soule, BP
Zarember, KA
Malech, HL
Holland, SM
Gallin, JI
AF Kuhns, Douglas B.
Alvord, W. Gregory
Heller, Theo
Feld, Jordan J.
Pike, Kristen M.
Marciano, Beatriz E.
Uzel, Gulbu
DeRavin, Suk See
Priel, Debra A. Long
Soule, Benjamin P.
Zarember, Kol A.
Malech, Harry L.
Holland, Steven M.
Gallin, John I.
TI Residual NADPH Oxidase and Survival in Chronic Granulomatous Disease.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID HEMATOLOGICALLY IMPORTANT MUTATIONS; MARROW-TRANSPLANTATION;
RESPIRATORY-BURST; INTERFERON-GAMMA; INVOLVEMENT; DEFICIENCY; GP91-PHOX;
INFECTION; THERAPY; DOMAIN
AB Background: Failure to generate phagocyte-derived superoxide and related reactive oxygen intermediates (ROIs) is the major defect in chronic granulomatous disease, causing recurrent infections and granulomatous complications. Chronic granulomatous disease is caused by missense, nonsense, frameshift, splice, or deletion mutations in the genes for p22(sup phox), p40(sup phox), p47(sup phox), p67(sup phox) (autosomal chronic granulomatous disease), or gp91(sup phox) (X-linked chronic granulomatous disease), which result in variable production of neutrophil-derived ROIs. We hypothesized that residual ROI production might be linked to survival in patients with chronic granulomatous disease.
Methods: We assessed the risks of illness and death among 287 patients with chronic granulomatous disease from 244 kindreds. Residual ROI production was measured with the use of superoxide-dependent ferricytochrome c reduction and flow cytometry with dihydrorhodamine oxidation assays. Expression of NADPH oxidase component protein was detected by means of immunoblotting, and the affected genes were sequenced to identify causal mutations.
Results: Survival of patients with chronic granulomatous disease was strongly associated with residual ROI production as a continuous variable, independently of the specific gene affected. Patients with mutations in p47(sup phox) and most missense mutations in gp91(sup phox) (with the exception of missense mutations in the nucleotide-binding and heme-binding domains) had more residual ROI production than patients with nonsense, frameshift, splice, or deletion mutations in gp91(sup phox). After adolescence, mortality curves diverged according to the extent of residual ROI production.
Conclusions: Patients with chronic granulomatous disease and modest residual production of ROI have significantly less severe illness and a greater likelihood of long-term survival than patients with little residual ROI production. The production of residual ROI is predicted by the specific NADPH oxidase mutation, regardless of the specific gene affected, and it is a predictor of survival in patients with chronic granulomatous disease. (Funded by the National Institutes of Health.)
N Engl J Med 2010;363:2600-10.
C1 [DeRavin, Suk See; Soule, Benjamin P.; Zarember, Kol A.; Malech, Harry L.; Gallin, John I.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA.
[Kuhns, Douglas B.; Priel, Debra A. Long] SAIC Frederick, Clin Serv Program, Frederick, MD USA.
[Pike, Kristen M.] SAIC Frederick, Lab Mol Technol, Frederick, MD USA.
[Alvord, W. Gregory] NCI Frederick, Biostat Consulting Div, Data Management Serv, Frederick, MD USA.
[Heller, Theo] NIDDKD, Liver Dis Branch, Bethesda, MD USA.
[Marciano, Beatriz E.; Uzel, Gulbu; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[DeRavin, Suk See; Soule, Benjamin P.; Zarember, Kol A.; Malech, Harry L.; Gallin, John I.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA.
[Feld, Jordan J.] Univ Toronto, Toronto Western Hosp, McLaughlin Rotman Ctr Global Hlth, Ctr Liver, Toronto, ON M5T 2S8, Canada.
RP Gallin, JI (reprint author), NIAID, Host Def Lab, NIH, Bldg 10,Rm 6-2551, Bethesda, MD 20892 USA.
EM jgallin@cc.nih.gov
FU National Institute of Allergy and Infectious Diseases [Z01-AI-000155,
Z01-AI-000645, Z01-AI-00646-06]; National Institute of Diabetes and
Digestive and Kidney Diseases [ZIA DK075008-04 LDB]; National Cancer
Institute [HH-SN261200800001E]; National Institutes of Health
FX Supported by intramural grants from the National Institute of Allergy
and Infectious Diseases (Z01-AI-000155, Z01-AI-000645, and
Z01-AI-00646-06), a grant from the National Institute of Diabetes and
Digestive and Kidney Diseases (ZIA DK075008-04 LDB), and a contract from
the National Cancer Institute (HH-SN261200800001E).; Funded by the
National Institutes of Health
NR 40
TC 166
Z9 170
U1 0
U2 9
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 DEC 30
PY 2010
VL 363
IS 27
BP 2600
EP 2610
DI 10.1056/NEJMoa1007097
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 700SD
UT WOS:000285763700005
PM 21190454
ER
PT J
AU Arinaminpathy, N
Grenfell, B
AF Arinaminpathy, Nimalan
Grenfell, Bryan
TI Dynamics of Glycoprotein Charge in the Evolutionary History of Human
Influenza
SO PLOS ONE
LA English
DT Article
ID A VIRUS; LINKED GLYCOSYLATION; RECEPTOR-BINDING; ANTIGENIC DRIFT;
HEMAGGLUTININ; PHENOTYPE; TURKEYS; GLYCANS; DOMAIN; SITES
AB Background: Influenza viruses show a significant capacity to evade host immunity; this is manifest both as large occasional jumps in the antigenic phenotype of viral surface molecules and in gradual antigenic changes leading to annual influenza epidemics in humans. Recent mouse studies show that avidity for host cells can play an important role in polyclonal antibody escape, and further that electrostatic charge of the hemagglutinin glycoprotein can contribute to such avidity.
Methodology/Principal Findings: We test the role of glycoprotein charge on sequence data from the three major subtypes of influenza A in humans, using a simple method of calculating net glycoprotein charge. Of all subtypes, H3N2 in humans shows a striking pattern of increasing positive charge since its introduction in 1968. Notably, this trend applies to both hemagglutinin and neuraminidase glycoproteins. In the late 1980s hemagglutinin charge reached a plateau, while neuraminidase charge started to decline. We identify key groups of amino acid sites involved in this charge trend.
Conclusions/Significance: To our knowledge these are the first indications that, for human H3N2, net glycoprotein charge covaries strongly with antigenic drift on a global scale. Further work is needed to elucidate how such charge interacts with other immune escape mechanisms, such as glycosylation, and we discuss important questions arising for future study.
C1 [Arinaminpathy, Nimalan; Grenfell, Bryan] Princeton Univ, Dept Ecol & Evolut Biol, Princeton, NJ 08544 USA.
[Grenfell, Bryan] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Arinaminpathy, N (reprint author), Princeton Univ, Dept Ecol & Evolut Biol, Princeton, NJ 08544 USA.
EM nimpathy@princeton.edu
FU National Institutes of Health [R01 GM083983-01]; National Science
Foundation [EF-0742373]; Department of Homeland Security Science and
Technology Directorate; Fogarty International Center, National
Institutes of Health
FX This research was supported by the National Institutes of Health grant
R01 GM083983-01 (www.nih.gov). Bryan Grenfell was also supported by the
National Science Foundation grant EF-0742373 and the Research and Policy
for Infectious Disease Dynamics (RAPIDD) program of the Department of
Homeland Security Science and Technology Directorate and the Fogarty
International Center, National Institutes of Health. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 25
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U1 1
U2 7
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 DEC 30
PY 2010
VL 5
IS 12
AR e15674
DI 10.1371/journal.pone.0015674
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 701DD
UT WOS:000285793600025
PM 21209885
ER
PT J
AU LeClair, CA
Boxer, MB
Thomas, CJ
Maloney, DJ
AF LeClair, Christopher A.
Boxer, Matthew B.
Thomas, Craig J.
Maloney, David J.
TI Total synthesis of LL-Z1640-2 utilizing a late-stage intramolecular
Nozaki-Hiyama-Kishi reaction
SO TETRAHEDRON LETTERS
LA English
DT Article
ID RESORCYLIC ACID LACTONES; CONVERGENT STEREOSPECIFIC SYNTHESIS; VINYLIC
ORGANOBORANES; ALKENYLBORONIC ACIDS; EFFICIENT SYNTHESIS; HYPOTHEMYCIN;
KINASE; STEREOCHEMISTRY; INHIBITION; MACROLIDES
AB A total synthesis of LL-Z1640-2 (2), a potent and selective kinase inhibitor, has been completed. The key step of the convergent synthesis utilized a late-stage intramolecular Nozaki-Hiyama-Kishi (NHK) reaction to close the macrocycle at the C6'-C7' bond. Published by Elsevier Ltd.
C1 [LeClair, Christopher A.; Boxer, Matthew B.; Thomas, Craig J.; Maloney, David J.] NHGRI, NIH Chem Genom Ctr, NIH, Rockville, MD 20850 USA.
RP Thomas, CJ (reprint author), NHGRI, NIH Chem Genom Ctr, NIH, 9800 Med Ctr Dr,Bldg B,Room 2055,MSC 3370, Bethesda, MD 20892 USA.
EM craigt@mail.nih.gov
FU Molecular Libraries Initiative of the National Institutes of Health
Roadmap for Medical Research; National Human Genome Research Institute;
National Institutes of Health
FX The authors thank William Leister for his assistance with normal and
reverse phase purification techniques. This research was supported by
the Molecular Libraries Initiative of the National Institutes of Health
Roadmap for Medical Research, the Intramural Research Program of the
National Human Genome Research Institute, and the National Institutes of
Health.
NR 45
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U1 4
U2 36
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0040-4039
J9 TETRAHEDRON LETT
JI Tetrahedron Lett.
PD DEC 29
PY 2010
VL 51
IS 52
BP 6852
EP 6855
DI 10.1016/j.tetlet.2010.10.092
PG 4
WC Chemistry, Organic
SC Chemistry
GA 699NP
UT WOS:000285670400014
PM 21516235
ER
PT J
AU Kanno, T
Nishizaki, T
Proia, RL
Kajimoto, T
Jahangeer, S
Okada, T
Nakamura, S
AF Kanno, T.
Nishizaki, T.
Proia, R. L.
Kajimoto, T.
Jahangeer, S.
Okada, T.
Nakamura, S.
TI REGULATION OF SYNAPTIC STRENGTH BY SPHINGOSINE 1-PHOSPHATE IN THE
HIPPOCAMPUS
SO NEUROSCIENCE
LA English
DT Article
DE sphingosine kinase; sphingosine 1 phosphate S1P receptor; long term
potentiation; hippocampus; memory
ID LONG-TERM POTENTIATION; NERVOUS-SYSTEM; LYSOPHOSPHOLIPID RECEPTORS;
SPHINGOSINE-1-PHOSPHATE; CELL; INVOLVEMENT; MICE
AB Although the hippocampus is a brain region involved in short term memory, the molecular mechanisms underlying memory formation are not completely under stood Here we show that sphingosine 1 phosphate (SIP) plays a pivotal role in the formation of memory Addition of SIP to rat hippocampal slices increased the rate of AMPA receptor mediated miniature excitatory postsynaptic cur rents (mEPSCs) recorded from the CA3 region of the hippocampus In addition long term potentiation (LTP) observed in the CA3 region was potently inhibited by a sphingosine kinase (SphK) inhibitor and this inhibition was fully reversed by SIP LIP was impaired in hippocampal slices specifically in the CA3 region obtained from SphK1 knockout mice, which correlates well with the poor performance of these animals in the Morris water maze test These results strongly suggest that SphK/S1P receptor signaling plays an important role in excitatory synaptic transmission in the CA3 region of hippocampus and has profound effects on hippocampal function such as spatial learning (C) 2010 IBRO Published by Elsevier Ltd All rights reserved
C1 [Kajimoto, T.; Jahangeer, S.; Okada, T.; Nakamura, S.] Kobe Univ, Grad Sch Med, Dept Mol & Cellular Biol, Div Biochem, Kobe, Hyogo 6500017, Japan.
[Proia, R. L.] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
[Kanno, T.; Nishizaki, T.] Hyogo Coll Med, Dept Physiol, Nishinomiya, Hyogo 6638501, Japan.
RP Nakamura, S (reprint author), Kobe Univ, Grad Sch Med, Dept Mol & Cellular Biol, Div Biochem, Kobe, Hyogo 6500017, Japan.
RI Proia, Richard/A-7908-2012
FU Ministry of Education Science Sports and Culture of Japan; Japan Society
for the Promotion of Science; Polish Academy of Sciences; National
Institutes of Health National Institute of Diabetes and Digestive and
Kidney Diseases USA; Osaka Medical Research Foundation for Incurable
Diseases
FX This work was supported in part by a Grant in-Aid for Scientific
Research (C) and a Grant-in-Aid for Scientific Research on Priority
Areas-Molecular Brain Science from the Ministry of Education Science
Sports and Culture of Japan the Bilateral Exchange Program between Japan
Society for the Promotion of Science and Polish Academy of Sciences the
Intramural Research Program of the National Institutes of Health
National Institute of Diabetes and Digestive and Kidney Diseases USA and
the Osaka Medical Research Foundation for Incurable Diseases
NR 26
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U1 0
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4522
J9 NEUROSCIENCE
JI Neuroscience
PD DEC 29
PY 2010
VL 171
IS 4
BP 973
EP 980
DI 10.1016/j.neuroscience.2010.10.021
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 693NO
UT WOS:000285231000002
PM 20950672
ER
PT J
AU Silverman, JL
Yang, M
Turner, SM
Katz, AM
Bell, DB
Koenig, JI
Crawley, JN
AF Silverman, J. L.
Yang, M.
Turner, S. M.
Katz, A. M.
Bell, D. B.
Koenig, J. I.
Crawley, J. N.
TI LOW STRESS REACTIVITY AND NEUROENDOCRINE FACTORS IN THE BTBR T(+)tf/J
MOUSE MODEL OF AUTISM
SO NEUROSCIENCE
LA English
DT Article
DE autism; mouse models BTBR
ID CORTICOTROPIN-RELEASING-FACTOR; ANXIETY-LIKE BEHAVIOR; TAIL SUSPENSION
TEST; SOCIAL APPROACH BEHAVIORS; MELANOCYTE-STIMULATING HORMONE;
GROOMING ANALYSIS ALGORITHM; COMPLEX MOVEMENT SEQUENCE; DOPAMINE D1
AGONISTS; MUTANT MICE DISPLAY; CRF-DEFICIENT MICE
AB Autism is a neurodevelopmental disorder characterized by abnormal reciprocal social interactions, communication deficits, and repetitive behaviors with restricted interests BTBR T+tf/J (BTBR) is an inbred mouse strain that displays robust behavioral phenotypes with analogies to all three of the diagnostic symptoms of autism, including low social interactions, reduced vocalizations in social settings, and high levels of repetitive self grooming Autism relevant phenotypes in BTBR offer translational tools to discover neurochemical mechanisms underlying unusual mouse behaviors relevant to symptoms of autism Because repetitive self grooming in mice may be a displacement behavior elevated by stressors, we investigated neuroendocrine markers of stress and behavioral reactivity to stressors in BTBR mice, as compared to C57BL/6J (86), a standard inbred strain with high sociability Radioimmunoassays replicated previous findings that circulating corticosterone is higher in BTBR than in B6 Higher basal glucocorticoid receptor mRNA and higher oxytocin peptide levels were detected in the brains of BTBR as compared to B6 No significant differences were detected in corticotrophin releasing factor (CRF) peptide or CRF mRNA In response to behavioral stressors, BTBR and B6 were generally similar on behavioral tasks including stress-induced hyperthermia elevated plus maze light dark exploration tail flick acoustic startle and prepulse inhibition BTBR displayed less reactivity than B6 to a noxious thermal stimulus in the hot plate, and less immobility than B6 in both the forced swim and tail suspension depression-related tasks BTBR, therefore, exhibited lower depression like scores than 136 on two standard tests sensitive to anti depressants, did not differ from B6 on two well validated anxiety like behaviors, and did not exhibit unusual stress reactivity to sensory stimuli Our findings support the interpretation that autism relevant social deficits, vocalizations, and repetitive behaviors are not the result of abnormal stress reactivity in the BTBR mouse model of autism Published by Elsevier Ltd on behalf of IBRO
C1 [Silverman, J. L.; Yang, M.; Turner, S. M.; Katz, A. M.; Crawley, J. N.] NIMH, Lab Behav Neurosci, Intramural Res Program, Bethesda, MD 20892 USA.
[Bell, D. B.; Koenig, J. I.] Univ Maryland, Sch Med, Dept Psychiat, Maryland Psychiat Res Ctr, Catonsville, MD 21228 USA.
RP Silverman, JL (reprint author), NIMH, Lab Behav Neurosci, Intramural Res Program, Bethesda, MD 20892 USA.
FU National Institute of Mental Health; Intramural Research Program; [R01
MH073826 JIK]
FX Supported by the National Institute of Mental Health Intramural Research
Program and R01 MH073826 JIK
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U2 12
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 DEC 29
PY 2010
VL 171
IS 4
BP 1197
EP 1208
DI 10.1016/j.neuroscience.2010.09.059
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 693NO
UT WOS:000285231000021
PM 20888890
ER
PT J
AU Hong, SB
Oh, H
Valera, VA
Baba, M
Schmidt, LS
Linehan, WM
AF Hong, Seung-Beom
Oh, HyoungBin
Valera, Vladimir A.
Baba, Masaya
Schmidt, Laura S.
Linehan, W. Marston
TI Inactivation of the FLCN Tumor Suppressor Gene Induces TFE3
Transcriptional Activity by Increasing Its Nuclear Localization
SO PLOS ONE
LA English
DT Article
ID HOGG-DUBE-SYNDROME; RENAL-CELL CARCINOMA; MELANOMA PROTEIN-B; BHD GENE;
THERAPEUTIC TARGET; MTOR ACTIVATION; BREAST-CANCER; AURISTATIN-E; MITF;
MICROPHTHALMIA
AB Background: Germline mutations in a tumor suppressor gene FLCN lead to development of fibrofolliculomas, lung cysts and renal cell carcinoma (RCC) in Birt-Hogg-Dube syndrome. TFE3 is a member of the MiTF/TFE transcription factor family and Xp11.2 translocations found in sporadic RCC involving TFE3 result in gene fusions and overexpression of chimeric fusion proteins that retain the C-terminal DNA binding domain of TFE3. We found that GPNMB expression, which is regulated by MiTF, was greatly elevated in renal cancer cells harboring either TFE3 translocations or FLCN inactivation. Since TFE3 is implicated in RCC, we hypothesized that elevated GPNMB expression was due to increased TFE3 activity resulting from the inactivation of FLCN.
Methodology/Principal Findings: TFE3 knockdown reduced GPNMB expression in renal cancer cells harboring either TFE3 translocations or FLCN inactivation. Moreover, FLCN knockdown induced GPNMB expression in FLCN-restored renal cancer cells. Conversely, wildtype FLCN suppressed GPNMB expression in FLCN-null cells. FLCN inactivation was correlated with increased TFE3 transcriptional activity accompanied by its nuclear localization as revealed by elevated GPNMB mRNA and protein expression, and predominantly nuclear immunostaining of TFE3 in renal cancer cells, mouse embryo fibroblast cells, mouse kidneys and mouse and human renal tumors. Nuclear localization of TFE3 was associated with TFE3 post-translational modifications including decreased phosphorylation.
Conclusions/Significance: Increased TFE3 activity is a downstream event induced by FLCN inactivation and is likely to be important for renal tumor development. This study provides an important novel mechanism for induction of TFE3 activity in addition to TFE3 overexpression resulting from Xp11.2 translocations, suggesting that TFE3 may be more broadly involved in tumorigenesis.
C1 [Hong, Seung-Beom; Oh, HyoungBin; Valera, Vladimir A.; Baba, Masaya; Schmidt, Laura S.; Linehan, W. Marston] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Schmidt, Laura S.] NCI, Basic Sci Program, SAIC Frederick Inc, Frederick, MD 21701 USA.
RP Hong, SB (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
EM linehanm@mail.nih.gov
RI Baba, Masaya/L-7490-2013; di Ronza, Alberto/H-7674-2016
OI Baba, Masaya/0000-0002-5308-6683; di Ronza, Alberto/0000-0002-9813-5143
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research; National Cancer Institute, National Institutes of
Health [HHSN261200800001E]; NCI-Frederick
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research. This project has been funded with federal funds from
the National Cancer Institute, National Institutes of Health, under
contract HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Heath and
Human Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the U.S. Government. The funder has
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript. SAIC-Frederick is the
Operation and Technical Support contractor to the National Cancer
Institute at Frederick (NCI-Frederick), a federal laboratory.
SAIC-Frederick, as the contractor, is the recipient of NCI-Frederick
funding and has not independently funded this research.
NR 43
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U1 0
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 DEC 29
PY 2010
VL 5
IS 12
AR e15793
DI 10.1371/journal.pone.0015793
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 701CZ
UT WOS:000285793200054
PM 21209915
ER
PT J
AU Lei, HY
Fukushige, T
Niu, W
Sarov, M
Reinke, V
Krause, M
AF Lei, Haiyan
Fukushige, Tetsunari
Niu, Wei
Sarov, Mihail
Reinke, Valerie
Krause, Michael
TI A Widespread Distribution of Genomic CeMyoD Binding Sites Revealed and
Cross Validated by ChIP-Chip and ChIP-Seq Techniques
SO PLOS ONE
LA English
DT Article
ID CAENORHABDITIS-ELEGANS; C-ELEGANS; MUSCLE DEVELOPMENT; GENE-EXPRESSION;
PROTEIN; TRANSCRIPTION; EMBRYO; MYOD; REGULATOR; INTESTINE
AB Identifying transcription factor binding sites genome-wide using chromatin immunoprecipitation (ChIP)-based technology is becoming an increasingly important tool in addressing developmental questions. However, technical problems associated with factor abundance and suitable ChIP reagents are common obstacles to these studies in many biological systems. We have used two completely different, widely applicable methods to determine by ChIP the genome-wide binding sites of the master myogenic regulatory transcription factor HLH-1 (CeMyoD) in C. elegans embryos. The two approaches, ChIP-seq and ChIP-chip, yield strongly overlapping results revealing that HLH-1 preferentially binds to promoter regions of genes enriched for E-box sequences (CANNTG), known binding sites for this well-studied class of transcription factors. HLH-1 binding sites were enriched upstream of genes known to be expressed in muscle, consistent with its role as a direct transcriptional regulator. HLH-1 binding was also detected at numerous sites unassociated with muscle gene expression, as has been previously described for its mouse homolog MyoD. These binding sites may reflect several additional functions for HLH-1, including its interactions with one or more co-factors to activate (or repress) gene expression or a role in chromatin organization distinct from direct transcriptional regulation of target genes. Our results also provide a comparison of ChIP methodologies that can overcome limitations commonly encountered in these types of studies while highlighting the complications of assigning in vivo functions to identified target sites.
C1 [Lei, Haiyan; Fukushige, Tetsunari; Krause, Michael] NIDDK, NIH, Bethesda, MD 20892 USA.
[Niu, Wei] Yale Univ, Dept Mol, New Haven, CT USA.
[Sarov, Mihail] Max Planck Inst Mol Cell Biol & Genet, Dresden, Germany.
[Reinke, Valerie] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA.
RP Lei, HY (reprint author), NIDDK, NIH, Bethesda, MD 20892 USA.
EM mwkrause@helix.nih.gov
RI NUI, WEI/B-8300-2011;
OI Krause, Michael/0000-0001-6127-3940
FU National Institutes of Health, National Institute of Diabetes and
Digestive and Kidney Diseases; National Human Genome Research Institute
[U01HG004267]
FX This work was supported, in part, by the Intramural Research Program of
the National Institutes of Health, National Institute of Diabetes and
Digestive and Kidney Diseases. Support also came from the Model Organism
Encylopedia of DNA Elements (modENCODE) project funded by grant
U01HG004267 from the National Human Genome Research Institute. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 45
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U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD DEC 29
PY 2010
VL 5
IS 12
AR e15898
DI 10.1371/journal.pone.0015898
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 701CZ
UT WOS:000285793200070
PM 21209968
ER
PT J
AU Ott, PA
Hamilton, A
Min, C
Safarzadeh-Amiri, S
Goldberg, L
Yoon, J
Yee, H
Buckley, M
Christos, PJ
Wright, JJ
Polsky, D
Osman, I
Liebes, L
Pavlick, AC
AF Ott, Patrick A.
Hamilton, Anne
Min, Christina
Safarzadeh-Amiri, Sara
Goldberg, Lauren
Yoon, Joanne
Yee, Herman
Buckley, Michael
Christos, Paul J.
Wright, John J.
Polsky, David
Osman, Iman
Liebes, Leonard
Pavlick, Anna C.
TI A Phase II Trial of Sorafenib in Metastatic Melanoma with Tissue
Correlates
SO PLOS ONE
LA English
DT Article
ID STAGE-IV MELANOMA; MALIGNANT-MELANOMA; B-RAF; BRAF; MUTATIONS;
DACARBAZINE; KIT; PROGRESSION; CARCINOMA; IMATINIB
AB Background: Sorafenib monotherapy in patients with metastatic melanoma was explored in this multi-institutional phase II study. In correlative studies the impact of sorafenib on cyclin D1 and Ki67 was assessed.
Methodology/Principal Findings: Thirty-six patients treatment-naive advanced melanoma patients received sorafenib 400 mg p.o. twice daily continuously. Tumor BRAF V600E mutational status was determined by routine DNA sequencing and mutation-specific PCR (MSPCR). Immunohistochemistry (IHC) staining for cyclin D1 and Ki67 was performed on available pre- and post treatment tumor samples. The main toxicities included diarrhea, alopecia, rash, mucositis, nausea, hand-foot syndrome, and intestinal perforation. One patient had a RECIST partial response (PR) lasting 175 days. Three patients experienced stable disease (SD) with a mean duration of 37 weeks. Routine BRAF V600E sequencing yielded 27 wild-type (wt) and 6 mutant tumors, whereas MSPCR identified 12 wt and 18 mutant tumors. No correlation was seen between BRAF V600E mutational status and clinical activity. No significant changes in expression of cyclin D1 or Ki67 with sorafenib treatment were demonstrable in the 15 patients with pre-and post-treatment tumor samples.
Conclusions/Significance: Sorafenib monotherapy has limited activity in advanced melanoma patients. BRAF V600E mutational status of the tumor was not associated with clinical activity and no significant effect of sorafenib on cyclin D1 or Ki67 was seen, suggesting that sorafenib is not an effective BRAF inhibitor or that additional signaling pathways are equally important in the patients who benefit from sorafenib. registration:
C1 [Ott, Patrick A.; Min, Christina; Safarzadeh-Amiri, Sara; Goldberg, Lauren; Buckley, Michael; Osman, Iman; Liebes, Leonard; Pavlick, Anna C.] NYU, Sch Med, Dept Med Oncol, New York, NY 10003 USA.
[Yee, Herman; Polsky, David] NYU, Sch Med, Dept Pathol, New York, NY USA.
[Yoon, Joanne; Polsky, David; Osman, Iman; Pavlick, Anna C.] NYU, Sch Med, Dept Dermatol, New York, NY USA.
[Hamilton, Anne] Royal Prince Alfred Hosp, Sydney Canc Ctr, Sydney, NSW, Australia.
[Hamilton, Anne] Univ Sydney, Sydney, NSW 2006, Australia.
[Hamilton, Anne] Sydney Melanoma Unit, Sydney, NSW, Australia.
[Christos, Paul J.] Weill Cornell Med Coll, Div Biostat & Epidemiol, New York, NY USA.
[Wright, John J.] NCI, Invest Drug Branch, Bethesda, MD 20892 USA.
RP Ott, PA (reprint author), NYU, Sch Med, Dept Med Oncol, New York, NY 10003 USA.
EM anna.pavlick@nyumc.org
FU United States Department of Health and Human Service [N01-CM-17103,
N01-CM-62204]
FX This work was supported by the United States Department of Health and
Human Service contracts [N01-CM-17103 and N01-CM-62204]. The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 38
TC 54
Z9 56
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 DEC 29
PY 2010
VL 5
IS 12
AR e15588
DI 10.1371/journal.pone.0015588
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 701CZ
UT WOS:000285793200030
PM 21206909
ER
PT J
AU Martos, A
Alfonso, C
Lopez-Navajas, P
Ahijado-Guzman, R
Mingorance, J
Minton, AP
Rivas, G
AF Martos, Ariadna
Alfonso, Carlos
Lopez-Navajas, Pilar
Ahijado-Guzman, Ruben
Mingorance, Jesus
Minton, Allen P.
Rivas, German
TI Characterization of Self-Association and Heteroassociation of Bacterial
Cell Division Proteins FtsZ and ZipA in Solution by Composition
Gradient-Static Light Scattering
SO BIOCHEMISTRY
LA English
DT Article
ID ESCHERICHIA-COLI; SEPTAL RING; QUANTITATIVE CHARACTERIZATION;
SEDIMENTATION EQUILIBRIUM; PROTOFILAMENTS; RECRUITMENT; ENERGETICS;
COMPONENT; POLYMERS; MONOMER
AB We have characterized the self-association of FtsZ in its GDP-bound state (GDP-FtsZ) and the heteroassociation of FtsZ and a soluble recombinant ZipA (sZipA) lacking the N-terminal transmembrane domain by means of composition gradient static light scattering (CG-SLS) and by measurement of sedimentation equilibrium. CG-SLS experiments at high ionic strengths and in the presence of 5 mM Mg(2+) show that, while FtsZ self-associates in a noncooperative fashion, sZipA acts as a monomer. CG-SLS data obtained from mixtures of FtsZ (A) and sZipA (B) in the presence of Mg(2+) are quantitatively described by an equilibrium model that takes into account significant scattering contributions from B, A(1), A(2), A(3), A(4), A(5), A(6), A(1)B, A(2)B, A(3)B, and A(4)B. However, in the absence of Mg(2+) (with EDTA), the data are best explained by an equilibrium model in which only B, A(1), A(2), A(3), A(1)B, and A(2)B contribute significantly to scattering. The best-fit molecular weights of monomeric A and B are in good agreement with values calculated from amino acid composition and with values obtained from sedimentation equilibrium. The latter technique also confirmed the interaction between sZipA and GDP-FtsZ. Moreover, the association model that best describes the CG-SLS data is in qualitative agreement with the sedimentation data. From these results, it follows that the binding of sZipA to GDP-FtsZ is of moderate affinity and does not significantly affect the interactions between FtsZ monomers. Under the working conditions used, only one sZipA binds to FtsZ oligomers with a length of six at most. The observed behavior would be compatible with FtsZ fibrils being anchored in vivo to the bacterial inner plasma membrane by substoichiometric binding of membrane-bound ZipA.
C1 [Martos, Ariadna; Alfonso, Carlos; Lopez-Navajas, Pilar; Ahijado-Guzman, Ruben; Rivas, German] CSIC, Ctr Invest Biol, Chem & Phys Biol Program, E-28040 Madrid, Spain.
[Mingorance, Jesus] CSIC, Ctr Nacl Biotecnol, Dept Mol Biotechnol, E-28040 Madrid, Spain.
[Minton, Allen P.] NIDDKD, Sect Phys Biochem, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA.
RP Rivas, G (reprint author), CSIC, Ctr Invest Biol, Chem & Phys Biol Program, Ramiro de Maeztu 9, E-28040 Madrid, Spain.
EM minton@helix.nih.gov; grivas@cib.csic.es
RI Mingorance, Jesus/B-7562-2009; Alfonso, Carlos/K-1316-2014;
Ahijado-Guzman, Ruben/F-7934-2016;
OI Mingorance, Jesus/0000-0001-6173-5711; Alfonso,
Carlos/0000-0001-7165-4800; Ahijado-Guzman, Ruben/0000-0002-9863-0443;
Minton, Allen/0000-0001-8459-1247; Rivas, German/0000-0003-3450-7478
FU Plan Nacional (Ministerio de Ciencia e Innovacion, Spain)
[BIO2008-04478-C03]; European Commision [DIVI-NOCELL
FP/HEALTH-F3-2009-223432]; Comunidad de Madrid [COMBACT
S-BIO-0260/2006]; National Institute of Diabetes and Digestive and
Kidney Diseases; European Social Fund
FX This work was supported by Plan Nacional (Ministerio de Ciencia e
Innovacion, Spain) Grants BIO2008-04478-C03 to G.R. Grant DIVI-NOCELL
FP/HEALTH-F3-2009-223432 (European Commision) to G.R., and Grant COMBACT
S-BIO-0260/2006 (Comunidad de Madrid) to J.M. and G.R. A.M. is a
predoctoral fellow from the Ministerio de Ciencia e Innovacion of Spain.
P.L.-N. was a recipient of a predoctoral fellowship from the Comunidad
de Madrid. The research of A.P.M. is supported by the Intramural
Research Program of the National Institute of Diabetes and Digestive and
Kidney Diseases. J.M. was the recipient of a Ramon y Cajal fellowship
financed by the Spanish Ministerio de Ciencia e Innovacion and the
European Social Fund.
NR 34
TC 21
Z9 21
U1 0
U2 3
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD DEC 28
PY 2010
VL 49
IS 51
BP 10780
EP 10787
DI 10.1021/bi101495x
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 696GF
UT WOS:000285429200004
PM 21082789
ER
PT J
AU Buch, I
Fishelovitch, D
London, N
Raveh, B
Wolfson, HJ
Nussinov, R
AF Buch, Idit
Fishelovitch, Dan
London, Nir
Raveh, Barak
Wolfson, Haim J.
Nussinov, Ruth
TI Allosteric Regulation of Glycogen Synthase Kinase 3 beta: A Theoretical
Study
SO BIOCHEMISTRY
LA English
DT Article
ID DEPENDENT PROTEIN-KINASE; STRUCTURAL BASIS; MOLECULAR-DYNAMICS;
CRYSTAL-STRUCTURE; TYROSINE PHOSPHORYLATION; SUBSTRATE-SPECIFICITY;
CATALYTIC-ACTIVITY; BETA-CATENIN; INHIBITORS; KINASE-3-BETA
AB Glycogen synthase kinase 3 beta (GSK-3 beta) is a serine-threonine kinase belonging to the CMGC family that plays a key role in many biological processes, such as glucose metabolism, cell cycle regulation, and proliferation. Like most protein kinases, GSK-3 beta is regulated via multiple pathways and sites. We performed all-atom molecular dynamics simulations on the unphosphorylated and phosphorylated unbound GSK-3 beta and the phosphorylated GSK-3 beta bound to a peptide substrate, its product, and a derived inhibitor. We found that GSK-3 beta autophosphorylation at residue Tyr(216) results in widening of the catalytic groove, thereby facilitating substrate access. In addition, we studied the interactions of the phosphorylated GSK-3 beta with a substrate and peptide inhibitor located at the active site and observed higher affinity of the inhibitor to the kinase. Furthermore, we detected a potential remote binding site which was previously identified in other kinases. In agreement with experiments we observed that binding of specific peptides at this remote site leads to stabilization of the activation loop located in the active site. We speculate that this stabilization could enhance the catalytic activity of the kinase. We point to this remote site as being structurally conserved and suggest that the allosteric phenomenon observed here may occur in the protein kinase superfamily.
C1 [Buch, Idit; Fishelovitch, Dan; Nussinov, Ruth] Tel Aviv Univ, Sackler Fac Med, Sackler Inst Mol Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel.
[London, Nir; Raveh, Barak] Hebrew Univ Jerusalem, Hadassah Med Sch, Fac Med, Dept Microbiol & Mol Genet,Inst Med Red IMRIC, IL-91120 Jerusalem, Israel.
[Raveh, Barak; Wolfson, Haim J.] Tel Aviv Univ, Raymond & Beverly Sackler Fac Exact Sci, Sch Comp Sci, IL-69978 Tel Aviv, Israel.
[Nussinov, Ruth] NCI Frederick, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA.
RP Nussinov, R (reprint author), Tel Aviv Univ, Sackler Fac Med, Sackler Inst Mol Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel.
EM ruthnu@helix.nih.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 number HHSN261200800001E. This research was supported (in part)
by the Intramural Research Program of the NIH, National Cancer
Institute, Center for Cancer Research.
NR 61
TC 13
Z9 13
U1 0
U2 5
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD DEC 28
PY 2010
VL 49
IS 51
BP 10890
EP 10901
DI 10.1021/bi100822q
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 696GF
UT WOS:000285429200016
PM 21105670
ER
PT J
AU Jin, LH
Tabe, Y
Kojima, K
Zhou, YX
Pittaluga, S
Konopleva, M
Miida, T
Raffeld, M
AF Jin, Linhua
Tabe, Yoko
Kojima, Kensuke
Zhou, Yixin
Pittaluga, Stefania
Konopleva, Marina
Miida, Takashi
Raffeld, Mark
TI MDM2 antagonist Nutlin-3 enhances bortezomib-mediated mitochondrial
apoptosis in TP53-mutated mantle cell lymphoma
SO CANCER LETTERS
LA English
DT Article
DE Mantle cell lymphoma; TP53; MDM2; Bortezomib; Nutlin-3
ID PROTEASOME INHIBITOR BORTEZOMIB; NON-HODGKINS-LYMPHOMA; PHASE-II;
DNA-DAMAGE; P53; ACTIVATION; SURVIVAL; NOXA; LINE; ESTABLISHMENT
AB This study demonstrated a pronounced synergistic growth-inhibitory effect of an MDM2 inhibitor Nutlin-3 and a proteasome inhibitor bortezomib in mantle cell lymphoma (MCL) cells regardless of TP53 mutant status and innate bortezomib sensitivity. In the mutant TP53 MCL cells which are intrinsically resistant to bortezomib, the combination of Nutlin-3/bortezomib synergistically induced cytotoxicity through the mitochondrial apoptotic pathway mediated by transcription-independent upregulation of NOXA, sequestration of MCL-1, activation of BAX, BAK, caspase-9 and -3. In the bortezomib sensitive wild-type TP53 MCL cells, the Nutlin-3/bortezomib combination caused G0/G1 cell cycle arrest followed by the increase in apoptosis induction. These findings indicate potential therapeutic efficacy of Nutlin-3/bortezomib combination for the treatment of chemorefractory MCL (c) 2010 Elsevier Ireland Ltd. All rights reserved.
C1 [Jin, Linhua; Tabe, Yoko; Zhou, Yixin; Miida, Takashi] Juntendo Univ, Sch Med, Dept Clin Pathol, Tokyo 113, Japan.
[Kojima, Kensuke] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA.
[Konopleva, Marina] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA.
[Pittaluga, Stefania; Raffeld, Mark] NCI, Hematopathol Sect, Pathol Lab, Bethesda, MD 20892 USA.
RP Tabe, Y (reprint author), Juntendo Univ, Sch Med, Dept Clin Lab Med, 2-1-1 Bunkyo Ku, Tokyo 113, Japan.
EM tabe@juntendo.ac.jp
RI Miida, Takashi/A-5589-2012
OI Miida, Takashi/0000-0002-4294-8030
FU Japan Science and Technology Agency; Japan Leukemia Research Fund; Osaka
Cancer Research Fund; Juntendo University School of Medicine
FX This work was supported by Grant-in-Aid for Scientific Research of the
Japan Science and Technology Agency, Japan Leukemia Research Fund, and
Osaka Cancer Research Fund (to Y.T.), and Project Research Program from
Juntendo University School of Medicine (to L.J.).
NR 34
TC 25
Z9 25
U1 0
U2 6
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3835
J9 CANCER LETT
JI Cancer Lett.
PD DEC 28
PY 2010
VL 299
IS 2
BP 161
EP 170
DI 10.1016/j.canlet.2010.08.015
PG 10
WC Oncology
SC Oncology
GA 690CE
UT WOS:000284977000008
PM 20850924
ER
PT J
AU Neuman, KC
AF Neuman, Keir C.
TI Evolutionary twist on topoisomerases: Conversion of gyrase to
topoisomerase IV
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Editorial Material
ID DNA TOPOISOMERASES; II TOPOISOMERASES
C1 NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA.
RP Neuman, KC (reprint author), NHLBI, Lab Mol Biophys, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM neumankc@nhlbi.nih.gov
RI Neuman, Keir/F-7400-2011
OI Neuman, Keir/0000-0002-0863-5671
FU Intramural NIH HHS
NR 14
TC 1
Z9 1
U1 0
U2 9
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD DEC 28
PY 2010
VL 107
IS 52
BP 22363
EP 22364
DI 10.1073/pnas.1016041108
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 699SX
UT WOS:000285684200005
PM 21169503
ER
PT J
AU Grundy, GJ
Yang, W
Gellert, M
AF Grundy, Gabrielle J.
Yang, Wei
Gellert, Martin
TI Autoinhibition of DNA cleavage mediated by RAG1 and RAG2 is overcome by
an epigenetic signal in V(D)J recombination
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE diversification; immunoglobulin gene; regulation
ID POSTCLEAVAGE COMPLEX; PLANT HOMEODOMAIN; C-TERMINUS; IN-VITRO;
TRANSPOSITION; EFFICIENT; LYSINE-4; PROTEINS; FINGER; MICE
AB Gene assembly of the variable domain of antigen receptors is initiated by DNA cleavage by the RAG1-RAG2 protein complex at sites flanking V, D, and J gene segments. Double-strand breaks are produced via a single-strand nick that is converted to a hairpin end on coding DNA and a blunt end on the neighboring recombination signal sequence. We demonstrate that the C-terminal regions of purified murine RAG1 (aa 1009-1040) and RAG2 (aa 388-520, including a plant homeodomain [PHD domain]) collaborate to inhibit the hairpinning stage of DNA cleavage. The C-terminal region of RAG2 stabilizes the RAG1/2 heterotetramer but destabilizes the RAG-DNA precleavage complex. This destabilization is reversed by binding of the PHD domain to a histone H3 peptide trimethylated on lysine 4 (H3K4me3). The addition of H3K4me3 likewise alleviates the RAG1/RAG2 C-terminus-mediated inhibition of hairpinning and the PHD-mediated inhibition of transposition activity. Thus a negative regulatory function of the noncore regions of RAG1/2 limits the RAG endonuclease activity in the absence of an activating methylated histone tail bound to the complex.
C1 [Grundy, Gabrielle J.; Yang, Wei; Gellert, Martin] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Gellert, M (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM gellert@helix.nih.gov
RI Yang, Wei/D-4926-2011
OI Yang, Wei/0000-0002-3591-2195
FU National Institute of Diabetes and Digestive and Kidney Diseases,
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,
National Institutes of Health.
NR 24
TC 26
Z9 26
U1 0
U2 2
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD DEC 28
PY 2010
VL 107
IS 52
BP 22487
EP 22492
DI 10.1073/pnas.1014958107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 699SX
UT WOS:000285684200029
PM 21149691
ER
PT J
AU Ming, M
Shea, CR
Guo, XM
Li, XL
Soltani, K
Han, WN
He, YY
AF Ming, Mei
Shea, Christopher R.
Guo, Xiumei
Li, Xiaoling
Soltani, Keyoumars
Han, Weinong
He, Yu-Ying
TI Regulation of global genome nucleotide excision repair by SIRT1 through
xeroderma pigmentosum C
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE UVB; PTEN; AKT
ID UV-INDUCED UBIQUITYLATION; UBIQUITIN LIGASE COMPLEX; DNA-DAMAGE
RESPONSE; TUMOR-SUPPRESSOR; LUNG-CANCER; IN-VIVO; MAMMALIAN SIRTUINS;
SKIN-CANCER; PROTEIN; XPC
AB Disruption of the nucleotide excision repair (NER) pathway by mutations can cause xeroderma pigmentosum, a syndrome predisposing affected individuals to development of skin cancer. The xeroderma pigmentosum C (XPC) protein is essential for initiating global genome NER by recognizing the DNA lesion and recruiting downstream factors. Here we show that inhibition of the deacetylase and longevity factor SIRT1 impairs global genome NER through suppressing the transcription of XPC in a SIRT1 deacetylase-dependent manner. SIRT1 enhances XPC expression by reducing AKT-dependent nuclear localization of the transcription repressor of XPC. Finally, we show that SIRT1 levels are significantly reduced inhuman skin tumors from Caucasian patients, a population at highest risk. These findings suggest that SIRT1 acts as a tumor suppressor through its role in DNA repair.
C1 [Ming, Mei; Shea, Christopher R.; Soltani, Keyoumars; Han, Weinong; He, Yu-Ying] Univ Chicago, Dept Med, Dermatol Sect, Chicago, IL 60637 USA.
[Guo, Xiumei; Li, Xiaoling] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA.
RP He, YY (reprint author), Univ Chicago, Dept Med, Dermatol Sect, 5841 S Maryland Ave, Chicago, IL 60637 USA.
EM yyhe@medicine.bsd.uchicago.edu
FU National Institutes of Health (NIH) [ES016936, Z01 ES102205,
UL1RR024999]; University of Chicago Comprehensive Cancer Center [P30
CA014599]; University of Chicago
FX We thank Terri Li for SIRT1 immunohistochemistry. We are grateful to Dr.
Pradip Raychaudhuri (University of Illinois, Chicago) for kindly
providing the XPC-Luc plasmids and to Dr. Ann Motten for critical
reading of the manuscript. This work was supported by National
Institutes of Health (NIH) Grant ES016936 (to Y.Y.H.), NIH Grant Z01
ES102205 (to X. L.), University of Chicago Comprehensive Cancer Center
Grant P30 CA014599, Clinical and Translational Science Award NIH Grant
UL1RR024999, and the University of Chicago Friends of Dermatology
Endowment Fund.
NR 69
TC 63
Z9 70
U1 0
U2 10
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD DEC 28
PY 2010
VL 107
IS 52
BP 22623
EP 22628
DI 10.1073/pnas.1010377108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 699SX
UT WOS:000285684200052
PM 21149730
ER
PT J
AU Tanaka, A
Cleland, MM
Xu, S
Narendra, DP
Suen, DF
Karbowski, M
Youle, RJ
AF Tanaka, Atsushi
Cleland, Megan M.
Xu, Shan
Narendra, Derek P.
Suen, Der-Fen
Karbowski, Mariusz
Youle, Richard J.
TI Proteasome and p97 mediate mitophagy and degradation of mitofusins
induced by Parkin
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
ID REGULATES MITOCHONDRIAL MORPHOLOGY; ENDOPLASMIC-RETICULUM; PROTEOLYTIC
CLEAVAGE; PROTEIN-DEGRADATION; PINK1; DISEASE; FUSION; MUTATIONS;
DROSOPHILA; FISSION
AB Damage to mitochondria can lead to the depolarization of the inner mitochondrial membrane, thereby sensitizing impaired mitochondria for selective elimination by autophagy. However, fusion of uncoupled mitochondria with polarized mitochondria can compensate for damage, reverse membrane depolarization, and obviate mitophagy. Parkin, an E3 ubiquitin ligase that is mutated in monogenic forms of Parkinson's disease, was recently found to induce selective autophagy of damaged mitochondria. Here we show that ubiquitination of mitofusins Mfn1 and Mfn2, large GTPases that mediate mitochondrial fusion, is induced by Parkin upon membrane depolarization and leads to their degradation in a proteasome-and p97-dependent manner. p97, a AAA+ ATPase, accumulates on mitochondria upon uncoupling of Parkin-expressing cells, and both p97 and proteasome activity are required for Parkin-mediated mitophagy. After mitochondrial fission upon depolarization, Parkin prevents or delays refusion of mitochondria, likely by the elimination of mitofusins. Inhibition of Drp1-mediated mitochondrial fission, the proteasome, or p97 prevents Parkin-induced mitophagy.
C1 [Tanaka, Atsushi; Cleland, Megan M.; Narendra, Derek P.; Suen, Der-Fen; Youle, Richard J.] NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Xu, Shan; Karbowski, Mariusz] Univ Maryland, Ctr Biomed Engn & Technol, Baltimore, MD 21201 USA.
[Xu, Shan; Karbowski, Mariusz] Univ Maryland, Dept Biochem & Mol Biol, Sch Med, Baltimore, MD 21201 USA.
RP Youle, RJ (reprint author), NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
EM mkarbowski@umaryland.edu; youler@ninds.nih.gov
RI Xu, Shan/F-7268-2014;
OI Harwig, Megan/0000-0003-2140-5739
FU National Institute of Neurological Disorders and Stroke; National
Institute of General Medical Sciences [R01: GM083131]; Japan Society for
the Promotion of Science
FX This work is supported by the National Institute of Neurological
Disorders and Stroke intramural program (to R.J. Youle), the National
Institute of General Medical Sciences (to M. Karbowski; R01: GM083131),
and the Japan Society for the Promotion of Science fellowship (to A.
Tanaka).
NR 57
TC 477
Z9 487
U1 6
U2 48
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 DEC 27
PY 2010
VL 191
IS 7
BP 1367
EP 1380
DI 10.1083/jcb.201007013
PG 14
WC Cell Biology
SC Cell Biology
GA 699SR
UT WOS:000285683600014
PM 21173115
ER
PT J
AU Chen, SR
Chen, H
Yuan, WX
Wess, J
Pan, HL
AF Chen, Shao-Rui
Chen, Hong
Yuan, Wei-Xiu
Wess, Juergen
Pan, Hui-Lin
TI Dynamic Control of Glutamatergic Synaptic Input in the Spinal Cord by
Muscarinic Receptor Subtypes Defined Using Knockout Mice
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID DORSAL-HORN NEURONS; ACETYLCHOLINE-RECEPTOR; CHOLINERGIC RECEPTORS;
AUTORADIOGRAPHIC LOCALIZATION; PROJECTION NEURONS; GABA(B) RECEPTORS;
GLYCINERGIC INPUT; NEUROPATHIC PAIN; GABAERGIC INPUTS; TRANSMISSION
AB Activation of muscarinic acetylcholine receptors (mAChRs) in the spinal cord inhibits pain transmission. At least three mAChR subtypes (M-2, M-3, andM(4)) are present in the spinal dorsal horn. However, it is not clear how each mAChR subtype contributes to the regulation of glutamatergic input to dorsal horn neurons. We recorded spontaneous excitatory postsynaptic currents (sEPSCs) from lamina II neurons in spinal cord slices from wild-type (WT) and mAChR subtype knock-out (KO) mice. The mAChR agonist oxotremorine-M increased the frequency of glutamatergic sEPSCs in 68.2% neurons from WT mice and decreased the sEPSC frequency in 21.2% neurons. Oxotremorine-M also increased the sEPSC frequency in similar to 50% neurons fromM(3)-single KO andM(1)/M-3 double-KO mice. In addition, the M-3 antagonist J104129 did not block the stimulatory effect of oxotremorine-M in the majority of neurons from WT mice. Strikingly, in M-5-single KO mice, oxotremorine-M increased sEPSCs in only 26.3% neurons, and J104129 abolished this effect. InM2/M-4 double-KO mice, but not M-2-or M-4-single KO mice, oxotremorine-M inhibited sEPSCs in significantly fewer neurons compared with WT mice, and blocking group II/III metabotropic glutamate receptors abolished this effect. The M-2/M-4 antagonist himbacine either attenuated the inhibitory effect of oxotremorine-M or potentiated the stimulatory effect of oxotremorine-M in WT mice. Our study demonstrates that activation of the M-2 and M-4 receptor subtypes inhibits synaptic glutamate release to dorsal horn neurons. M-5 is the predominant receptor subtype that potentiates glutamatergic synaptic transmission in the spinal cord.
C1 [Chen, Shao-Rui] Univ Texas MD Anderson Canc Ctr, Dept Anesthesiol & Perioperat Med, Unit 110, Houston, TX 77030 USA.
[Wess, Juergen] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Chen, SR (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Anesthesiol & Perioperat Med, Unit 110, 1515 Holcombe Blvd, Houston, TX 77030 USA.
EM schen@mdanderson.org
FU National Institutes of Health [GM64830, NS45602]; N.G. and Helen T.
Hawkins endowment
FX This work was supported, in whole or in part, by Grants GM64830 and
NS45602 from the National Institutes of Health and by the N.G. and Helen
T. Hawkins endowment (to H.-L. P.).
NR 44
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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 DEC 24
PY 2010
VL 285
IS 52
BP 40427
EP 40437
DI 10.1074/jbc.M110.176966
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 696AN
UT WOS:000285414400005
PM 20940295
ER
PT J
AU Prasad, R
Shock, DD
Beard, WA
Wilson, SH
AF Prasad, Rajendra
Shock, David D.
Beard, William A.
Wilson, Samuel H.
TI Substrate Channeling in Mammalian Base Excision Repair Pathways: Passing
the Baton
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID DNA-POLYMERASE-BETA; DEOXYRIBOSE PHOSPHATE LYASE; LIGASE-I; BOVINE
TESTIS; IDENTIFICATION; MECHANISM; CELLS; RECONSTITUTION; BINDING;
PROTEIN
AB The current model for base excision repair (BER) involves two general sub-pathways termed single-nucleotide BER and long patch BER that are distinguished by their repair patch sizes and the enzymes/co-factors involved. Both sub-pathways involve a series of sequential steps from initiation to completion of repair. The BER sub-pathways are designed to sequester the various intermediates, passing them along from one step to the next without allowing these toxic molecules to trigger cell cycle arrest, necrotic cell death, or apoptosis. Although a variety of DNA-protein and protein-protein interactions are known for the BER intermediates and enzymes/co-factors, the molecular mechanisms accounting for step-to-step coordination are not well understood. In the present study we designed an in vitro assay to explore the question of whether there is a channeling or "hand-off" of the repair intermediates during BER in vitro. The results show that when BER enzymes are pre-bound to the initial single-nucleotide BER intermediate, the DNA is channeled from apurinic/apyrimidinic endonuclease 1 to DNA polymerase beta and then to DNA ligase. In the long patch BER subpathway, where the 5'-end of the incised strand is blocked, the intermediate after DNA polymerase beta gap filling is not channeled to the subsequent enzyme, flap endonuclease 1. Instead, flap endonuclease 1 must recognize and bind to the intermediate in competition with other molecules.
C1 [Prasad, Rajendra; Shock, David D.; Beard, William A.; Wilson, Samuel H.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Wilson, SH (reprint author), 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM wilson5@niehs.nih.gov
FU National Institutes of Health Research [Z01-ES050158, Z01-ES050159];
NIEHS
FX This work was supported, in whole or in part, by National Institutes of
Health Research Projects Z01-ES050158 and Z01-ES050159 in the Intramural
Research Program of the NIEHS.
NR 44
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U1 0
U2 1
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD DEC 24
PY 2010
VL 285
IS 52
BP 40479
EP 40488
DI 10.1074/jbc.M110.155267
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 696AN
UT WOS:000285414400010
PM 20952393
ER
PT J
AU Noh, OJ
Park, YH
Chung, YW
Kim, IY
AF Noh, Ok Jeong
Park, Yong Hwan
Chung, Youn Wook
Kim, Ick Young
TI Transcriptional Regulation of Selenoprotein W by MyoD during Early
Skeletal Muscle Differentiation
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID MYOGENIC DIFFERENTIATION; OXIDATIVE STRESS; BINDING PROTEIN; MYOBLAST
CELLS; DNA-BINDING; STEM-CELLS; EXPRESSION; GENE; THIOREDOXIN;
ACTIVATION
AB Selenoprotein W (SelW) is expressed in various tissues, but it is especially high in the skeletal muscle of mammals. Such tissue-specific protein expression implies regulation by a tissue-specific factor. In this study, we investigated SelW expression during myogenic C2C12 cell differentiation using RTPCR, quantitative PCR, and Western blot analysis. Both the protein and mRNA levels of SelW were increased during C2C12 cell differentiation, particularly during the early stage. Sequence analysis of the SelW promoter revealed four putative E-boxes, E1, E2, E3, and E4, which are known binding sites for MyoD, a myogenic transcriptional factor. Luciferase reporter assay showed that E1 and E4 were crucial for MyoD-dependent promoter activity. Using EMSA analysis, we observed that MyoD bound directly to E1 but not to E4, even though E4 mutation reduced SelW promoter activity in the luciferase reporter assay. Binding of MyoD to E1 was further investigated by ChIP assay. These results suggest that the SelW gene was activated by the binding of MyoD to a specific E-box during early skeletal muscle differentiation.
C1 [Noh, Ok Jeong; Park, Yong Hwan; Kim, Ick Young] Korea Univ, Lab Cellular & Mol Biochem, Sch Life Sci & Biotechnol, Seoul 136701, South Korea.
[Chung, Youn Wook] NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA.
RP Kim, IY (reprint author), Korea Univ, Lab Cellular & Mol Biochem, Sch Life Sci & Biotechnol, Seoul 136701, South Korea.
EM ickkim@korea.ac.kr
FU Korean Government (MOEHRD) [KRF-2005-070-C00086]; Korea University
FX This work was authored, in whole or in part, by National Institutes of
Health staff. This work was funded by Korea Research Foundation Grant
from the Korean Government (MOEHRD) KRF-2005-070-C00086 (to I. Y. K.)
and in part by a Korea University grant.
NR 41
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U1 1
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 DEC 24
PY 2010
VL 285
IS 52
BP 40496
EP 40507
DI 10.1074/jbc.M110.152934
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 696AN
UT WOS:000285414400012
PM 20956524
ER
PT J
AU Park, H
Boyington, JC
AF Park, HaJeung
Boyington, Jeffrey C.
TI The 1.5 angstrom Crystal Structure of Human Receptor for Advanced
Glycation Endproducts (RAGE) Ectodomains Reveals Unique Features
Determining Ligand Binding
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID END-PRODUCTS RAGE; CELL-SURFACE RECEPTOR; PATTERN-RECOGNITION; SCAVENGER
RECEPTORS; ALZHEIMERS-DISEASE; NMR SYSTEM; PROTEINS; ACTIVATION; S100B;
CRYSTALLOGRAPHY
AB Interaction of the pattern recognition receptor, RAGE with key ligands such as advanced glycation end products (AGE), S100 proteins, amyloid beta, and HMGB1 has been linked to diabetic complications, inflammatory and neurodegenerative disorders, and cancer. To help answer the question of how a single receptor can recognize and respond to a diverse set of ligands we have investigated the structure and binding properties of the first two extracellular domains of human RAGE, which are implicated in various ligand binding and subsequent signaling events. The 1.5-angstrom crystal structure reveals an elongated molecule with a large basic patch and a large hydrophobic patch, both highly conserved. Isothermal titration calorimetry (ITC) and deletion experiments indicate S100B recognition by RAGE is an entropically driven process involving hydrophobic interaction that is dependent on Ca2+ and on residues in the C'D loop (residues 54-67) of domain 1. In contrast, competition experiments using gel shift assays suggest that RAGE interaction with AGE is driven by the recognition of negative charges on AGE-proteins. We also demonstrate that RAGE can bind to dsDNA and dsRNA. These findings reveal versatile structural features of RAGE that help explain its ability to recognize of multiple ligands.
C1 [Park, HaJeung; Boyington, Jeffrey C.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Park, H (reprint author), Scripps Res Inst, Jupiter, FL 33458 USA.
EM hajpark@scripps.edu; boyingtonj@niaid.nih.gov
FU National Institutes of Health, NIEHS
FX This work was supported, in whole or in part, by the Intramural Research
Program of the National Institutes of Health, NIEHS.
NR 49
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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 DEC 24
PY 2010
VL 285
IS 52
BP 40762
EP 40770
DI 10.1074/jbc.M110.169276
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 696AN
UT WOS:000285414400040
PM 20943659
ER
PT J
AU Kohli, RM
Maul, RW
Guminski, AF
McClure, RL
Gajula, KS
Saribasak, H
McMahon, MA
Siliciano, RF
Gearhart, PJ
Stivers, JT
AF Kohli, Rahul M.
Maul, Robert W.
Guminski, Amy F.
McClure, Rhonda L.
Gajula, Kiran S.
Saribasak, Huseyin
McMahon, Moira A.
Siliciano, Robert F.
Gearhart, Patricia J.
Stivers, James T.
TI Local Sequence Targeting in the AID/APOBEC Family Differentially Impacts
Retroviral Restriction and Antibody Diversification
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; INDUCED CYTIDINE DEAMINASE; CLASS SWITCH
RECOMBINATION; SOMATIC HYPERMUTATION; HUMAN APOBEC3G; HIV-1 INFECTION;
DNA INTEGRATION; IN-VIVO; AID; CELLS
AB Nucleic acid cytidine deaminases of the activation-induced deaminase (AID)/APOBEC family are critical players in active and innate immune responses, playing roles as target-directed, purposeful mutators. AID specifically deaminates the host immunoglobulin (Ig) locus to evolve antibody specificity, whereas its close relative, APOBEC3G (A3G), lethally mutates the genomes of retroviral pathogens such as HIV. Understanding the basis for the target-specific action of these enzymes is essential, as mistargeting poses significant risks, potentially promoting oncogenesis (AID) or fostering drug resistance (A3G). AID prefers to deaminate cytosine in WRC (W = A/T, R = A/G) motifs, whereas A3G favors deamination of CCC motifs. This specificity is largely dictated by a single, divergent protein loop in the enzyme family that recognizes the DNA sequence. Through grafting of this substrate-recognition loop, we have created enzyme variants of A3G and AID with altered local targeting to directly evaluate the role of sequence specificity on immune function. We find that grafted loops placed in the A3G scaffold all produced efficient restriction of HIV but that foreign loops in the AID scaffold compromised hypermutation and class switch recombination. Local targeting, therefore, appears alterable for innate defense against retroviruses by A3G but important for adaptive antibody maturation catalyzed by AID. Notably, AID targeting within the Ig locus is proportionally correlated to its in vitro ability to target WRC sequences rather than non-WRC sequences. Although other mechanisms may also contribute, our results suggest that local sequence targeting by AID/APOBEC3 enzymes represents an elegant example of co-evolution of enzyme specificity with its target DNA sequence.
C1 [Maul, Robert W.; McClure, Rhonda L.; Saribasak, Huseyin; Gearhart, Patricia J.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
[Kohli, Rahul M.; Gajula, Kiran S.; Siliciano, Robert F.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Guminski, Amy F.; McMahon, Moira A.; Stivers, James T.] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA.
RP Gearhart, PJ (reprint author), NIA, Lab Mol Gerontol, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM gearhartp@mail.nih.gov; jstivers@jhmi.edu
RI Saribasak, Huseyin/C-9331-2012;
OI Saribasak, Huseyin/0000-0003-0055-062X; Maul,
Robert/0000-0002-6958-8514; Kohli, Rahul/0000-0002-7689-5678
FU NIA; National Institutes of Health; [GM06669]; [GM056834];
[KAI089242A]
FX This work was supported, in whole or in part, by NIA, National
Institutes of Health (Intramural Research Program), T32 Grant GM06669,
and Grants GM056834 (to J. T. S.) and KAI089242A (to R. M. K.).
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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 DEC 24
PY 2010
VL 285
IS 52
BP 40956
EP 40964
DI 10.1074/jbc.M110.177402
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 696AN
UT WOS:000285414400059
PM 20929867
ER
PT J
AU Jain, S
Tillinger, A
Mopidevi, B
Pandey, VG
Chauhan, CK
Fiering, SN
Warming, S
Kumar, A
AF Jain, Sudhir
Tillinger, Andrej
Mopidevi, Brahmaraju
Pandey, Varunkumar G.
Chauhan, Chetankumar K.
Fiering, Steven N.
Warming, Soren
Kumar, Ashok
TI Transgenic Mice with -6A Haplotype of the Human Angiotensinogen Gene
Have Increased Blood Pressure Compared with -6G Haplotype
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; PHOSPHOENOLPYRUVATE CARBOXYKINASE;
ESSENTIAL-HYPERTENSION; MOLECULAR-GENETICS; PROMOTER ACTIVITY; HUMAN
RENIN; C/EBP BETA; EXPRESSION; TRANSCRIPTION; RAT
AB Hypertension is a serious risk factor for cardiovascular disease, and the angiotensinogen (AGT) gene locus is associated with human essential hypertension. The human AGT (hAGT) gene has an A/G polymorphism at -6, and the -6A allele is associated with increased blood pressure. However, transgenic mice containing 1.2 kb of the promoter with -6A of the hAGT gene show neither increased plasma AGT level nor increased blood pressure compared with -6G. We have found that the hAGT gene has three additional SNPs (A/G at -1670, C/G at -1562, and T/G at -1561). Variants -1670A, -1562C, and -1561T almost always occur with -6A, and variants -1670G, -1562G, and -1561G almost always occur with -6G. Therefore, the hAGT gene may be subdivided into either -6A or -6G haplotypes. We show that these polymorphisms affect the binding of HNF-1 alpha and glucocorticoid receptor to the promoter, and a reporter construct containing a 1.8-kb hAGT gene promoter with -6A haplotype has 4-fold increased glucocorticoid-induced promoter activity as compared with -6G haplotype. In order to understand the physiological significance of these haplotypes in an in vivo situation, we have generated double transgenic mice containing either the -6A or -6G haplotype of the hAGT gene and the human renin gene. Our ChIP assay shows that HNF-1 alpha and glucocorticoid receptor have stronger affinity for the chromatin obtained from the liver of transgenic mice containing -6A haplotype. Our studies also show that transgenic mice containing -6A haplotype have increased plasma AGT level and increased blood pressure as compared with -6G haplotype. Our studies explain the molecular mechanism involved in association of the -6A allele of the hAGT gene with hypertension.
C1 [Jain, Sudhir; Tillinger, Andrej; Mopidevi, Brahmaraju; Pandey, Varunkumar G.; Chauhan, Chetankumar K.; Kumar, Ashok] New York Med Coll, Dept Pathol, Valhalla, NY 10595 USA.
[Fiering, Steven N.] Dartmouth Med Sch, Dept Microbiol Immunol & Genet, Hanover, NH 03755 USA.
[Warming, Soren] NCI Frederick, Mouse Canc Genet Program, NIH, Frederick, MD 21702 USA.
RP Kumar, A (reprint author), New York Med Coll, Dept Pathol, Rm 455,Basic Sci Bldg, Valhalla, NY 10595 USA.
EM ashok_kumar@nymc.edu
RI Mopidevi, Brahmaraju/D-6003-2015
FU National Institutes of Health [HL081752, HL66296]
FX This work was supported, in whole or in part, by National Institutes of
Health Grants HL081752 and HL66296 (to A. K.).
NR 52
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U1 0
U2 0
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD DEC 24
PY 2010
VL 285
IS 52
BP 41172
EP 41186
DI 10.1074/jbc.M110.167585
PG 15
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 696AN
UT WOS:000285414400079
PM 20978123
ER
PT J
AU Chen, J
Petrus, M
Bryant, BR
Nguyen, VP
Goldman, CK
Bamford, R
Morris, JC
Janik, JE
Waldmann, TA
AF Chen, Jing
Petrus, Mike
Bryant, Bonita R.
Nguyen, Vinh Phuc
Goldman, Carolyn K.
Bamford, Richard
Morris, John C.
Janik, John E.
Waldmann, Thomas A.
TI Autocrine/paracrine cytokine stimulation of leukemic cell proliferation
in smoldering and chronic adult T-cell leukemia
SO BLOOD
LA English
DT Article
ID VIRUS TYPE-I; KAPPA-B SITE; HTLV-I; GENE-EXPRESSION; TAX PROTEIN;
DOWN-REGULATION; INTERLEUKIN-2; PROGRESSION; LYMPHOMA; CLONES
AB Adult T-cell leukemia (ATL), a heterogeneous disease, can be divided into smoldering, chronic, lymphoma, and acute types clinically. In addition to different clinical manifestations, different stages of ATL have different molecular signatures. Here, we demonstrated that smoldering/chronic ATL peripheral blood mononuclear cells spontaneously proliferated ex vivo in a cytokine (interleukin -12 [IL-12]/IL-9/IL-15)-dependent manner, while acute-type ATL peripheral blood mononuclear cells did not proliferate or proliferated independent of cytokines. Smoldering/chronic ATL cells produced IL-2 and IL-9 in 6-day ex vivo cultures. Interestingly, the addition of an anti-IL-2R-alpha monoclonal antibody profoundly inhibited IL-9 expression, suggesting optimal expression of IL-9 was dependent on IL-2 signaling in these patients. To determine whether there would be autonomous proliferation of ATL leukemic cells, we purified leukemic cells from patients with smoldering/chronic ATL. Purified leukemic cells cultured alone produced IL-2/IL-9, and the downstream Janus kinase/signal transducer and activator of transcription pathway was activated. However, the leukemic cells did not proliferate independently, but required coculture with autologous monocytes to induce proliferation. Moreover, interaction between leukemic cells and monocytes was contact dependent, and major histocompatibility complex class II expression may have contributed to this interaction. In conclusion, our data provide evidence that there is autocrine/paracrine cytokine stimulation of leukemic cell proliferation in patients with smoldering/chronic ATL that could be targeted for treatment. (Blood. 2010;116(26):5948-5956)
C1 [Waldmann, Thomas A.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Waldmann, TA (reprint author), NCI, Metab Branch, Ctr Canc Res, NIH, Bldg 10,Rm 4N115,10 Ctr Dr, Bethesda, MD 20892 USA.
EM tawald@helix.nih.gov
FU National Cancer Institute, National Institutes of Health
FX This study was supported by the intramural research program of the
National Cancer Institute, National Institutes of Health.
NR 37
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U1 2
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 DEC 23
PY 2010
VL 116
IS 26
BP 5948
EP 5956
DI 10.1182/blood-2010-04-277418
PG 9
WC Hematology
SC Hematology
GA 698GX
UT WOS:000285583400025
PM 20858854
ER
PT J
AU Kovtunovych, G
Eckhaus, MA
Ghosh, MC
Ollivierre-Wilson, H
Rouault, TA
AF Kovtunovych, Gennadiy
Eckhaus, Michael A.
Ghosh, Manik C.
Ollivierre-Wilson, Hayden
Rouault, Tracey A.
TI Dysfunction of the heme recycling system in heme oxygenase 1-deficient
mice: effects on macrophage viability and tissue iron distribution
SO BLOOD
LA English
DT Article
ID RECEPTOR-MEDIATED UPTAKE; SCAVENGER RECEPTOR; HEMOPEXIN; DEFICIENCY;
HEMOGLOBIN; PROTEIN; LIVER; TRANSPORT; DISEASE; CELL
AB To better understand the tissue iron overload and anemia previously reported in a human patient and mice that lack heme oxygenase-1 (HO-1), we studied iron distribution and pathology in HO-1(Hmox1)(-/-) mice. We found that resident splenic and liver macrophages were mostly absent in HO-1(-/-) mice. Erythrophagocytosis caused the death of HO-1(-/-) macrophages in in vitro experiments, supporting the hypothesis that HO-1(-/-) macrophages died of exposure to heme released on erythrophagocytosis. Rupture of HO-1(-/-) macro-phages in vivo and release of nonmetabolized heme probably caused tissue inflammation. In the spleen, initial splenic enlargement progressed to red pulp fibrosis, atrophy, and functional hyposplenism in older mice, recapitulating the asplenia of an HO-1-deficient patient. We postulate that the failure of tissue macrophages to remove senescent erythrocytes led to intravascular hemolysis and increased expression of the heme and hemoglobin scavenger proteins, hemopexin and haptoglobin. Lack of macro-phages expressing the haptoglobin receptor, CD163, diminished the ability of haptoglobin to neutralize circulating hemoglobin, and iron overload occurred in kidney proximal tubules, which were able to catabolize heme with HO-2. Thus, in HO-1(-/-) mammals, the reduced function and viability of erythrophagocytosing macrophages are the main causes of tissue damage and iron redistribution. (Blood. 2010; 116(26):6054-6062)
C1 [Kovtunovych, Gennadiy; Ghosh, Manik C.; Ollivierre-Wilson, Hayden; Rouault, Tracey A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Mol Med, Bethesda, MD 20892 USA.
[Eckhaus, Michael A.] NIH, Div Vet Resources, Off Res Serv, Off Director, Bethesda, MD 20892 USA.
RP Rouault, TA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Mol Med, 9000 Rockville Pike,Bldg 18T,Rm 101, Bethesda, MD 20892 USA.
EM trou@helix.nih.gov
FU National Institute of Child Health and Human Development
FX This work was supported by the National Institute of Child Health and
Human Development (intramural program).
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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 DEC 23
PY 2010
VL 116
IS 26
BP 6054
EP 6062
DI 10.1182/blood-2010-03-272138
PG 9
WC Hematology
SC Hematology
GA 698GX
UT WOS:000285583400037
PM 20844238
ER
PT J
AU Johnson, ST
Newton, AS
Chopra, M
Buckingham, J
Huang, TTK
Franks, PW
Jetha, MM
Ball, GDC
AF Johnson, Steven T.
Newton, Amanda S.
Chopra, Meera
Buckingham, Jeanette
Huang, Terry T. K.
Franks, Paul W.
Jetha, Mary M.
Ball, Geoff D. C.
TI In search of quality evidence for lifestyle management and glycemic
control in children and adolescents with type 2 diabetes: A systematic
review
SO BMC PEDIATRICS
LA English
DT Review
ID IMPAIRED GLUCOSE-TOLERANCE; FOLLOW-UP; YOUTH; MELLITUS; PREVALENCE;
EPIDEMIC; OBESITY; HEALTH; YOUNG; INTERVENTIONS
AB Background: Our purpose was to evaluate the impact of lifestyle behavior modification on glycemic control among children and youth with clinically defined Type 2 Diabetes (T2D).
Methods: We conducted a systematic review of studies (randomized trials, quasi-experimental studies) evaluating lifestyle (diet and/or physical activity) modification and glycemic control (HbA1c). Our data sources included bibliographic databases (EMBASE, CINAHL (R), Cochrane Library, Medline (R), PASCAL, PsycINFO (R), and Sociological Abstracts), manual reference search, and contact with study authors. Two reviewers independently selected studies that included any intervention targeting diet and/or physical activity alone or in combination as a means to reduce HbA1c in children and youth under the age of 18 with T2D.
Results: Our search strategy generated 4,572 citations. The majority of citations were not relevant to the study objective. One study met inclusion criteria. In this retrospective study, morbidly obese youth with T2D were treated with a very low carbohydrate diet. This single study received a quality index score of < 11, indicating poor study quality and thus limiting confidence in the study's conclusions.
Conclusions: There is no high quality evidence to suggest lifestyle modification improves either short- or long-term glycemic control in children and youth with T2D. Additional research is clearly warranted to define optimal lifestyle behaviour strategies for young people with T2D.
C1 [Newton, Amanda S.; Jetha, Mary M.; Ball, Geoff D. C.] Univ Alberta, Dept Pediat, Aberhart Ctr 8213, Edmonton, AB T6G 2P3, Canada.
[Johnson, Steven T.] Athabasca Univ, Ctr Nursing & Hlth Studies, Fac Hlth Disciplines, Athabasca, AB, Canada.
[Chopra, Meera] Mt Sinai Hosp, Toronto, ON M5T 3L9, Canada.
[Buckingham, Jeanette] Univ Alberta, John W Scott Hlth Sci Lib, Edmonton, AB T6G 2R7, Canada.
[Huang, Terry T. K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Franks, Paul W.] Umea Univ Hosp, Genet Epidemiol & Clin Res Grp, Dept Publ Hlth & Clin Med, Div Med, S-90185 Umea, Sweden.
RP Ball, GDC (reprint author), Univ Alberta, Dept Pediat, Aberhart Ctr 8213, 11402 Univ Ave, Edmonton, AB T6G 2P3, Canada.
EM geoff.ball@ualberta.ca
OI Franks, Paul/0000-0002-0520-7604
FU V sterbotten's Health Authority; Swedish Heart-Lung Foundation
[20070633]; Swedish Diabetes Association [DIA2006-013]; Canadian
Institutes of Health Research [CIHR]; Alberta Innovates - Health
Solutions
FX STJ, MC, JB, and TT-KH received no external support. PWF is supported by
V sterbotten's Health Authority (ALF strategic appointment 2006-2009),
the Swedish Heart-Lung Foundation (20070633), and the Swedish Diabetes
Association (DIA2006-013). ASN is supported by a Career Development
Award from the Canadian Child Health Clinician Scientist Program (funded
by the Canadian Institutes of Health Research [CIHR]). GDCB is supported
by a Population Health Investigator Award from Alberta Innovates -
Health Solutions and a New Investigator Award from CIHR. These study
sponsors did not play any role in this research or in the decision to
submit the paper for publication. Contents of the publication do not
necessarily represent the views or policies of the National Institutes
of Health.
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PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2431
J9 BMC PEDIATR
JI BMC Pediatr.
PD DEC 23
PY 2010
VL 10
AR 97
DI 10.1186/1471-2431-10-97
PG 8
WC Pediatrics
SC Pediatrics
GA 703HR
UT WOS:000285969500001
PM 21182791
ER
PT J
AU Kiselev, E
Dexheimer, TS
Pommier, Y
Cushman, M
AF Kiselev, Evgeny
Dexheimer, Thomas S.
Pommier, Yves
Cushman, Mark
TI Design, Synthesis, and Evaluation of Dibenzo[c,h][1,6]naphthyridines as
Topoisomerase I Inhibitors and Potential Anticancer Agents
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID DNA TOPOISOMERASES; DRUG; CAMPTOTHECIN; CYTOTOXICITY; OPTIMIZATION;
HETEROCYCLES; COMPLEXES; COVALENT; NITROGEN; CHLORIDE
AB Indenoisoquinoline topoisomerase I (Top 1) inhibitors are a novel class of anticancer agents. Modifications of the indenoisoquinoline A, B, and D rings have been extensively studied in order to optimize Top 1 inhibitory activity and cytotoxicity. To improve understanding of the forces that stabilize drug-Top1-DNA ternary complexes, the five-membered cyclopentadienone C-ring of the indenoisoquinoline system was replaced by six-membered nitrogen heterocyclic rings, resulting in dibenzo[c,h][1,6]naphthyridines that were synthesized by a novel route and tested for Top 1 inhibition. This resulted in several compounds that have unique DNA cleavage site selectivities and potent antitumor activities in a number of cancer cell lines.
C1 [Kiselev, Evgeny; Cushman, Mark] Purdue Univ, Dept Med Chem & Mol Pharmacol, Sch Pharm, W Lafayette, IN 47907 USA.
[Kiselev, Evgeny; Cushman, Mark] Purdue Univ, Purdue Ctr Canc Res, W Lafayette, IN 47907 USA.
[Dexheimer, Thomas S.; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Cushman, M (reprint author), Purdue Univ, Dept Med Chem & Mol Pharmacol, Sch Pharm, W Lafayette, IN 47907 USA.
EM cushman@purdue.edu
FU NIH, Center for Cancer Research, National Cancer Institute; National
Institute of Health (NIH) [UO1 CA89566]
FX TD and YP are supported by the NIH Intramural Program, Center for Cancer
Research, National Cancer Institute. This work was made possible by the
National Institute of Health (NIH) through support of this work with
Research Grant UO1 CA89566.
NR 39
TC 32
Z9 32
U1 0
U2 10
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
J9 J MED CHEM
JI J. Med. Chem.
PD DEC 23
PY 2010
VL 53
IS 24
BP 8716
EP 8726
DI 10.1021/jm101048k
PG 11
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 693ZQ
UT WOS:000285264300024
PM 21090809
ER
PT J
AU Sa, JM
Twu, O
AF Sa, Juliana M.
Twu, Olivia
TI Protecting the malaria drug arsenal: halting the rise and spread of
amodiaquine resistance by monitoring the PfCRT SVMNT type
SO MALARIA JOURNAL
LA English
DT Editorial Material
ID PLASMODIUM-FALCIPARUM MALARIA; CHLOROQUINE-RESISTANCE; CESSATION;
TANZANIA; EFFICACY; MALAWI; GENE
AB The loss of chloroquine due to selection and spread of drug resistant Plasmodium falciparum parasites has greatly impacted malaria control, especially in highly endemic areas of Africa. Since chloroquine removal a decade ago, the guidelines to treat falciparum malaria suggest combination therapies, preferentially with an artemisinin derivative. One of the recommended partner drugs is amodiaquine, a pro-drug that relies on its active metabolite monodesethylamodiaquine, and is still effective in areas of Africa, but not in regions of South America. Genetic studies on P. falciparum parasites have shown that different pfcrt mutant haplotypes are linked to distinct levels of chloroquine and amodiaquine responses. The pfcrt haplotype SVMNT (termed after the amino acids from codon positions 72-76) is stably present in several areas where amodiaquine was introduced and widely used. Parasites with this haplotype are highly resistant to monodesethylamodiaquine and also resistant to chloroquine. The presence of this haplotype in Africa was found for the first time in 2004 in Tanzania and a role for amodiaquine in the selection of this haplotype was suggested. This commentary discusses the finding of a second site in Africa with high incidence of this haplotype. The >50% SVMNT haplotype prevalence in Angola represents a threat to the rise and spread of amodiaquine resistance. It is paramount to monitor pfcrt haplotypes in every country currently using amodiaquine and to re-evaluate current combination therapies in areas where SVMNT type parasites are prevalent.
C1 [Sa, Juliana M.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
[Twu, Olivia] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA.
RP Sa, JM (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy,Room 3E-10C, Rockville, MD 20852 USA.
EM jsa@niaid.nih.gov
OI Twu, Olivia/0000-0002-5175-3016
FU Intramural NIH HHS
NR 13
TC 29
Z9 30
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1475-2875
J9 MALARIA J
JI Malar. J.
PD DEC 23
PY 2010
VL 9
AR 374
DI 10.1186/1475-2875-9-374
PG 3
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA 724VS
UT WOS:000287604900003
PM 21182787
ER
PT J
AU Bevilacqua, L
Doly, S
Kaprio, J
Yuan, QP
Tikkanen, R
Paunio, T
Zhou, ZF
Wedenoja, J
Maroteaux, L
Diaz, S
Belmer, A
Hodgkinson, CA
Dell'Osso, L
Suvisaari, J
Coccaro, E
Rose, RJ
Peltonen, L
Virkkunen, M
Goldman, D
AF Bevilacqua, Laura
Doly, Stephane
Kaprio, Jaakko
Yuan, Qiaoping
Tikkanen, Roope
Paunio, Tiina
Zhou, Zhifeng
Wedenoja, Juho
Maroteaux, Luc
Diaz, Silvina
Belmer, Arnaud
Hodgkinson, Colin A.
Dell'Osso, Liliana
Suvisaari, Jaana
Coccaro, Emil
Rose, Richard J.
Peltonen, Leena
Virkkunen, Matti
Goldman, David
TI A population-specific HTR2B stop codon predisposes to severe impulsivity
SO NATURE
LA English
DT Article
ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; MONOAMINE-OXIDASE;
MOLECULAR-GENETICS; MALE-MICE; SEROTONIN; BEHAVIOR; VULNERABILITY;
PREDICTS; DOPAMINE; MUTATION
AB Impulsivity, describing action without foresight, is an important feature of several psychiatric diseases, suicidality and violent behaviour. The complex origins of impulsivity hinder identification of the genes influencing it and the diseases with which it is associated. Here we perform exon-focused sequencing of impulsive individuals in a founder population, targeting fourteen genes belonging to the serotonin and dopamine domain. A stop codon in HTR2B was identified that is common (minor allele frequency >1%) but exclusive to Finnish people. Expression of the gene in the human brain was assessed, as well as the molecular functionality of the stop codon, which was associated with psychiatric diseases marked by impulsivity in both population and family-based analyses. Knockout of Htr2b increased impulsive behaviours in mice, indicative of predictive validity. Our study shows the potential for identifying and tracing effects of rare alleles in complex behavioural phenotypes using founder populations, and indicates a role for HTR2B in impulsivity.
C1 [Bevilacqua, Laura; Yuan, Qiaoping; Zhou, Zhifeng; Hodgkinson, Colin A.; Goldman, David] NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA.
[Doly, Stephane; Maroteaux, Luc; Diaz, Silvina; Belmer, Arnaud] INSERM, UMR S 839, F-75654 Paris, France.
[Doly, Stephane; Maroteaux, Luc; Diaz, Silvina; Belmer, Arnaud] Univ Paris 06, Inst du Fer Moulin, F-75654 Paris, France.
[Kaprio, Jaakko] Univ Helsinki, Dept Publ Hlth, FI-00014 Helsinki, Finland.
[Kaprio, Jaakko] Inst Mol Med, FI-00014 Helsinki, Finland.
[Kaprio, Jaakko] Natl Inst Hlth & Welf, Unit Child & Adolescent Psychiat, FI-00271 Helsinki, Finland.
[Tikkanen, Roope; Virkkunen, Matti] Univ Helsinki, Inst Clin Med, Dept Psychiat, FI-00014 Helsinki, Finland.
[Paunio, Tiina; Suvisaari, Jaana] Univ Helsinki, Dept Psychiat, Cent Hosp, FI-00014 Helsinki, Finland.
[Wedenoja, Juho] Univ Helsinki, Dept Med Genet, FI-00014 Helsinki, Finland.
[Wedenoja, Juho] Univ Helsinki, Inst Mol Med Finland, FI-00014 Helsinki, Finland.
[Wedenoja, Juho] Natl Inst Hlth & Welf, FI-00014 Helsinki, Finland.
[Dell'Osso, Liliana] Univ Pisa, Dept Psychiat, I-56100 Pisa, Italy.
[Coccaro, Emil] Univ Chicago, Pritzker Sch Med, Dept Psychiat, Chicago, IL 60637 USA.
[Rose, Richard J.] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN 47405 USA.
[Virkkunen, Matti] Kellokoski Psychiat Hosp, FI-04500 Kellokoski, Finland.
RP Goldman, D (reprint author), NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA.
EM davidgoldman@mail.nih.gov
RI Goldman, David/F-9772-2010;
OI Goldman, David/0000-0002-1724-5405; Maroteaux, Luc/0000-0002-9499-8603;
Wedenoja, Juho/0000-0002-6155-0378; Kaprio, Jaakko/0000-0002-3716-2455
FU National Institute on Alcohol Abuse and Alcoholism, NIH; Academy of
Finland Centre of Excellence in Complex Disease Genetics; National
Institute on Alcohol Abuse and Alcoholism [AA-12502, AA-09203]; Academy
of Finland [100499, 205585, 118555]; Centre National de la Recherche
Scientifique; Institut National de la Sante et de la Recherche Medicale;
Universite Pierre et Marie Curie; Fondation de France; Fondation pour la
Recherche Medicale; French Ministry of Research (Agence Nationale pour
la Recherche); European Union; IBRO; Region Ile de France DIM STEM
FX This study is dedicated to the memory of L.P. and M. Linnoila. We thank
L. Akhtar for assistance with tissue culture, C. Marietta for assistance
with measurement of receptor protein levels, V. Srivastava and G. Yamini
for discussions, and P.-H. Shen for contributions to ancestry analyses.
M. Eggert and L. Brown assisted with clinical ascertainment and
assessment of the University of Helsinki sample. We thank M. Linnoila
for his contributions to the collection of the University of Helsinki
sample. E. Kempas assisted with genotyping. J.-M. Launay measured plasma
testosterone levels in Htr2b-/- mice. We also thank A.
Tuulio-Henriksson, E. Vuoksimaa, A. Happola and L. Arala. This work was
supported by the Intramural Research Program of the National Institute
on Alcohol Abuse and Alcoholism, NIH and the Academy of Finland Centre
of Excellence in Complex Disease Genetics. The FinnTwin12 and FinnTwin16
studies were supported by the National Institute on Alcohol Abuse and
Alcoholism (AA-12502 and AA-09203 to R.J.R.), and by the Academy of
Finland (100499, 205585 and 118555 to J.K.). The studies on
Htr2b-/- mice were supported by the Centre National de la
Recherche Scientifique, the Institut National de la Sante et de la
Recherche Medicale, the Universite Pierre et Marie Curie, and by grants
from the Fondation de France, the Fondation pour la Recherche Medicale,
the French Ministry of Research (Agence Nationale pour la Recherche),
and the European Union. L.M.'s team is an "Equipe Fondation pour la
Recherche Medicale''. S. Diaz is supported by a fellowship from IBRO and
Region Ile de France DIM STEM.
NR 39
TC 100
Z9 111
U1 2
U2 19
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD DEC 23
PY 2010
VL 468
IS 7327
BP 1061
EP U460
DI 10.1038/nature09629
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 697XT
UT WOS:000285553800050
PM 21179162
ER
PT J
AU Jatoi, I
Anderson, WF
AF Jatoi, Ismail
Anderson, William F.
TI Lessons from the Mammography Wars
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
ID CANCER
C1 [Jatoi, Ismail] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Anderson, William F.] NCI, Rockville, MD USA.
RP Jatoi, I (reprint author), Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
EM jatoi@uthscsa.edu
NR 7
TC 1
Z9 1
U1 0
U2 1
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 DEC 23
PY 2010
VL 363
IS 26
BP 2569
EP 2570
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 697YL
UT WOS:000285555600029
PM 21175333
ER
PT J
AU Cai, ML
Huang, Y
Craigie, R
Clore, GM
AF Cai, Mengli
Huang, Ying
Craigie, Robert
Clore, G. Marius
TI Structural Basis of the Association of HIV-1 Matrix Protein with DNA
SO PLOS ONE
LA English
DT Article
ID PARAMAGNETIC RELAXATION ENHANCEMENT; VIRUS TYPE-1 MATRIX;
NUCLEAR-LOCALIZATION SIGNAL; DIPOLAR COUPLINGS; CRYSTAL-STRUCTURES;
NONDIVIDING CELLS; MACROMOLECULES; INFECTION; BINDING; DOMAIN
AB HIV-1 matrix (MA) is a multifunctional protein that is synthesized as a polyprotein that is cleaved by protease during viral maturation. MA contains a cluster of basic residues whose role is controversial. Proposed functions include membrane anchoring, facilitating viral assembly, and directing nuclear import of the viral DNA. Since MA has been reported to be a component of the preintegration complex (PIC), we have used NMR to probe its interaction with other PIC components. We show that MA interacts with DNA and this is likely sufficient to account for its association with the PIC.
C1 [Cai, Mengli; Clore, G. Marius] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Huang, Ying; Craigie, Robert] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Cai, ML (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA.
EM robertc@mail.nih.gov; mariusc@mail.nih.gov
RI Clore, G. Marius/A-3511-2008
OI Clore, G. Marius/0000-0003-3809-1027
FU NIDDK; NIH; Office of the Director of the NIH
FX This work was supported by the Intramural Program of NIDDK, NIH and by
the AIDS Targeted Antiviral Program of the Office of the Director of the
NIH (to G.M.C. and R.C.). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 28
TC 13
Z9 14
U1 0
U2 5
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 DEC 23
PY 2010
VL 5
IS 12
AR e15675
DI 10.1371/journal.pone.0015675
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 698FO
UT WOS:000285579200028
PM 21203471
ER
PT J
AU Mukhopadhyay, P
Mukherjee, S
Ahsan, K
Bagchi, A
Pacher, P
Das, DK
AF Mukhopadhyay, Partha
Mukherjee, Subhendu
Ahsan, Kaimul
Bagchi, Angshuman
Pacher, Pal
Das, Dipak K.
TI Restoration of Altered MicroRNA Expression in the Ischemic Heart with
Resveratrol
SO PLOS ONE
LA English
DT Article
ID BREAST-CANCER CELLS; NITRIC-OXIDE; SURVIVAL SIGNAL; MECHANISM; STRESS;
CARDIOPROTECTION; PROGNOSIS; DIAGNOSIS; PATHWAY; SIRT1
AB Background: Resveratrol, a constituent of red wine, is important for cardioprotection. MicroRNAs are known regulators for genes involved in resveratrol-mediated cardiac remodeling and the regulatory pathway involving microRNA has not been studied so far.
Methods: We explored the cardioprotection by resveratrol in ischemia/reperfusion model of rat and determined cardiac functions. miRNA profile was determined from isolated RNA using quantitative Real-time PCR based array. Systemic analyses of miRNA array and theirs targets were determined using a number of computational approaches.
Results: Cardioprotection by resveratrol and its derivative in ischemia/reperfusion [I/R] rat model was examined with miRNA expression profile. Unique expression pattern were found for each sample, particularly with resveratrol [pure compound] and longevinex [commercial resveratrol formulation] pretreated hearts. Longevinex and resveratrol pretreatment modulates the expression pattern of miRNAs close to the control level based on PCA analyses. Differential expression was observed in over 25 miRNAs, some of them, such as miR-21 were previously implicated in cardiac remodeling. The target genes for the differentially expressed miRNA include genes of various molecular function such as metal ion binding, sodium-potassium ion, transcription factors, which may play key role in reducing I/R injury.
Conclusion: Rats pretreated with resveratrol for 3 weeks leads to significant cardioprotection against ischemia/reperfusion injury. A unique signature of miRNA profile is observed in control heart pretreated with resveratrol or longevinex. We have determined specific group of miRNA in heart that have altered during IR injuries. Most of those altered microRNA expressions modulated close to their basal level in resveratrol or longevinex treated I/R mice.
C1 [Mukhopadhyay, Partha; Pacher, Pal] NIAAA, Lab Physiol Studies, NIH, Bethesda, MD USA.
[Bagchi, Angshuman] Buck Inst Age Res, Novato, CA USA.
[Mukherjee, Subhendu; Ahsan, Kaimul; Das, Dipak K.] Univ Connecticut, Sch Med, Cardiovasc Res Ctr, Farmington, CT USA.
RP Mukhopadhyay, P (reprint author), NIAAA, Lab Physiol Studies, NIH, Bethesda, MD USA.
EM ddas@neuron.uchc.edu
RI MUKHOPADHYAY, PARTHA/G-3890-2010; Pacher, Pal/B-6378-2008;
OI MUKHOPADHYAY, PARTHA/0000-0002-1178-1274; Pacher,
Pal/0000-0001-7036-8108; Mukherjee, Subhendu/0000-0002-4851-4428
FU NIH [HL 34360, HL 22559, HL 33889]; NIAAA/NIH
FX This study was supported in part by NIH HL 34360, HL 22559 and HL 33889
(to D. K. Das) and Intramural Research Program of the NIAAA/NIH (to P.
Pacher). The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 38
TC 43
Z9 46
U1 0
U2 7
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 DEC 23
PY 2010
VL 5
IS 12
AR e15705
DI 10.1371/journal.pone.0015705
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 698FO
UT WOS:000285579200031
PM 21203465
ER
PT J
AU Johnson, WE
Onorato, DP
Roelke, ME
Land, ED
O'Brien, SJ
AF Johnson, Warren E.
Onorato, David P.
Roelke, Melody E.
Land, E. Darrell
O'Brien, Stephen J.
TI Genetic Future for Florida Panthers Response
SO SCIENCE
LA English
DT Letter
C1 [Johnson, Warren E.; Roelke, Melody E.; O'Brien, Stephen J.] NCI, SAIC Frederick, Lab Genom Divers, Frederick, MD 21702 USA.
[Onorato, David P.; Land, E. Darrell] Florida Fish & Wildlife Conservat Commiss, Naples, FL 34114 USA.
RP Johnson, WE (reprint author), NCI, SAIC Frederick, Lab Genom Divers, Frederick, MD 21702 USA.
EM warjohns@mail.nih.gov
RI Johnson, Warren/D-4149-2016
OI Johnson, Warren/0000-0002-5954-186X
NR 0
TC 1
Z9 1
U1 3
U2 34
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 DEC 23
PY 2010
VL 330
IS 6012
BP 1744
EP 1744
DI 10.1126/science.330.6012.1744-b
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 698OS
UT WOS:000285603700011
ER
PT J
AU Gerstein, MB
Lu, ZJ
Van Nostrand, EL
Cheng, C
Arshinoff, BI
Liu, T
Yip, KY
Robilotto, R
Rechtsteiner, A
Ikegami, K
Alves, P
Chateigner, A
Perry, M
Morris, M
Auerbach, RK
Feng, X
Leng, J
Vielle, A
Niu, W
Rhrissorrakrai, K
Agarwal, A
Alexander, RP
Barber, G
Brdlik, CM
Brennan, J
Brouillet, JJ
Carr, A
Cheung, MS
Clawson, H
Contrino, S
Dannenberg, LO
Dernburg, AF
Desai, A
Dick, L
Dose, AC
Du, JA
Egelhofer, T
Ercan, S
Euskirchen, G
Ewing, B
Feingold, EA
Gassmann, R
Good, PJ
Green, P
Gullier, F
Gutwein, M
Guyer, MS
Habegger, L
Han, T
Henikoff, JG
Henz, SR
Hinrichs, A
Holster, H
Hyman, T
Iniguez, AL
Janette, J
Jensen, M
Kato, M
Kent, WJ
Kephart, E
Khivansara, V
Khurana, E
Kim, JK
Kolasinska-Zwierz, P
Lai, EC
Latorre, I
Leahey, A
Lewis, S
Lloyd, P
Lochovsky, L
Lowdon, RF
Lubling, Y
Lyne, R
MacCoss, M
Mackowiak, SD
Mangone, M
Mckay, S
Mecenas, D
Merrihew, G
Miller, DM
Muroyama, A
Murray, JI
Ooi, SL
Pham, H
Phippen, T
Preston, EA
Rajewsky, N
Ratsch, G
Rosenbaum, H
Rozowsky, J
Rutherford, K
Ruzanov, P
Sarov, M
Sasidharan, R
Sboner, A
Scheid, P
Segal, E
Shin, HJ
Shou, C
Slack, FJ
Slightam, C
Smith, R
Spencer, WC
Stinson, EO
Taing, S
Takasaki, T
Vafeados, D
Voronina, K
Wang, GL
Washington, NL
Whittle, CM
Wu, BJ
Yan, KK
Zeller, G
Zha, Z
Zhong, M
Zhou, XL
Ahringer, J
Strome, S
Gunsalus, KC
Micklem, G
Liu, XS
Reinke, V
Kim, SK
Hillier, LW
Henikoff, S
Piano, F
Snyder, M
Stein, L
Lieb, JD
Waterston, RH
AF Gerstein, Mark B.
Lu, Zhi John
Van Nostrand, Eric L.
Cheng, Chao
Arshinoff, Bradley I.
Liu, Tao
Yip, Kevin Y.
Robilotto, Rebecca
Rechtsteiner, Andreas
Ikegami, Kohta
Alves, Pedro
Chateigner, Aurelien
Perry, Marc
Morris, Mitzi
Auerbach, Raymond K.
Feng, Xin
Leng, Jing
Vielle, Anne
Niu, Wei
Rhrissorrakrai, Kahn
Agarwal, Ashish
Alexander, Roger P.
Barber, Galt
Brdlik, Cathleen M.
Brennan, Jennifer
Brouillet, Jeremy Jean
Carr, Adrian
Cheung, Ming-Sin
Clawson, Hiram
Contrino, Sergio
Dannenberg, Luke O.
Dernburg, Abby F.
Desai, Arshad
Dick, Lindsay
Dose, Andrea C.
Du, Jiang
Egelhofer, Thea
Ercan, Sevinc
Euskirchen, Ghia
Ewing, Brent
Feingold, Elise A.
Gassmann, Reto
Good, Peter J.
Green, Phil
Gullier, Francois
Gutwein, Michelle
Guyer, Mark S.
Habegger, Lukas
Han, Ting
Henikoff, Jorja G.
Henz, Stefan R.
Hinrichs, Angie
Holster, Heather
Hyman, Tony
Iniguez, A. Leo
Janette, Judith
Jensen, Morten
Kato, Masaomi
Kent, W. James
Kephart, Ellen
Khivansara, Vishal
Khurana, Ekta
Kim, John K.
Kolasinska-Zwierz, Paulina
Lai, Eric C.
Latorre, Isabel
Leahey, Amber
Lewis, Suzanna
Lloyd, Paul
Lochovsky, Lucas
Lowdon, Rebecca F.
Lubling, Yaniv
Lyne, Rachel
MacCoss, Michael
Mackowiak, Sebastian D.
Mangone, Marco
Mckay, Sheldon
Mecenas, Desirea
Merrihew, Gennifer
Miller, David M., III
Muroyama, Andrew
Murray, John I.
Ooi, Siew-Loon
Pham, Hoang
Phippen, Taryn
Preston, Elicia A.
Rajewsky, Nikolaus
Raetsch, Gunnar
Rosenbaum, Heidi
Rozowsky, Joel
Rutherford, Kim
Ruzanov, Peter
Sarov, Mihail
Sasidharan, Rajkumar
Sboner, Andrea
Scheid, Paul
Segal, Eran
Shin, Hyunjin
Shou, Chong
Slack, Frank J.
Slightam, Cindie
Smith, Richard
Spencer, William C.
Stinson, E. O.
Taing, Scott
Takasaki, Teruaki
Vafeados, Dionne
Voronina, Ksenia
Wang, Guilin
Washington, Nicole L.
Whittle, Christina M.
Wu, Beijing
Yan, Koon-Kiu
Zeller, Georg
Zha, Zheng
Zhong, Mei
Zhou, Xingliang
Ahringer, Julie
Strome, Susan
Gunsalus, Kristin C.
Micklem, Gos
Liu, X. Shirley
Reinke, Valerie
Kim, Stuart K.
Hillier, LaDeana W.
Henikoff, Steven
Piano, Fabio
Snyder, Michael
Stein, Lincoln
Lieb, Jason D.
Waterston, Robert H.
CA modENCODE Consortium
TI Integrative Analysis of the Caenorhabditis elegans Genome by the
modENCODE Project
SO SCIENCE
LA English
DT Article
ID C. ELEGANS; NUCLEOSOME ORGANIZATION; TRANSCRIPTION FACTORS; RNA-SEQ;
REVEALS; EXPRESSION; EMBRYOS; NETWORK; DNA; CHROMATIN
AB We systematically generated large-scale data sets to improve genome annotation for the nematode Caenorhabditis elegans, a key model organism. These data sets include transcriptome profiling across a developmental time course, genome-wide identification of transcription factor-binding sites, and maps of chromatin organization. From this, we created more complete and accurate gene models, including alternative splice forms and candidate noncoding RNAs. We constructed hierarchical networks of transcription factor-binding and microRNA interactions and discovered chromosomal locations bound by an unusually large number of transcription factors. Different patterns of chromatin composition and histone modification were revealed between chromosome arms and centers, with similarly prominent differences between autosomes and the X chromosome. Integrating data types, we built statistical models relating chromatin, transcription factor binding, and gene expression. Overall, our analyses ascribed putative functions to most of the conserved genome.
C1 [Gerstein, Mark B.; Lu, Zhi John; Cheng, Chao; Yip, Kevin Y.; Robilotto, Rebecca; Alves, Pedro; Auerbach, Raymond K.; Leng, Jing; Alexander, Roger P.; Habegger, Lukas; Lochovsky, Lucas; Rozowsky, Joel; Sboner, Andrea; Shou, Chong; Yan, Koon-Kiu] Yale Univ, Program Computat Biol & Bioinformat, New Haven, CT 06520 USA.
[Gerstein, Mark B.; Lu, Zhi John; Cheng, Chao; Yip, Kevin Y.; Agarwal, Ashish; Alexander, Roger P.; Rozowsky, Joel; Sasidharan, Rajkumar; Sboner, Andrea; Yan, Koon-Kiu] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA.
[Gerstein, Mark B.; Agarwal, Ashish; Du, Jiang] Yale Univ, Dept Comp Sci, New Haven, CT 06511 USA.
[Van Nostrand, Eric L.; Brdlik, Cathleen M.; Brouillet, Jeremy Jean; Kim, Stuart K.; Snyder, Michael] Stanford Univ, Med Ctr, Dept Genet, Stanford, CA 94305 USA.
[Arshinoff, Bradley I.; Perry, Marc; Feng, Xin; Kephart, Ellen; Lloyd, Paul; Ruzanov, Peter; Zha, Zheng; Stein, Lincoln] Ontario Inst Canc Res, Toronto, ON M5G 0A3, Canada.
[Arshinoff, Bradley I.; Stein, Lincoln] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A1, Canada.
[Liu, Tao; Shin, Hyunjin; Taing, Scott; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Liu, Tao; Shin, Hyunjin; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Ikegami, Kohta; Brennan, Jennifer; Ercan, Sevinc; Jensen, Morten; Whittle, Christina M.; Zhou, Xingliang; Lieb, Jason D.] Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA.
[Ikegami, Kohta; Brennan, Jennifer; Ercan, Sevinc; Jensen, Morten; Whittle, Christina M.; Zhou, Xingliang; Lieb, Jason D.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA.
[Chateigner, Aurelien; Carr, Adrian; Contrino, Sergio; Gullier, Francois; Lyne, Rachel; Rutherford, Kim; Smith, Richard; Micklem, Gos] Univ Cambridge, Dept Genet, Cambridge CB2 3EH, England.
[Chateigner, Aurelien; Carr, Adrian; Contrino, Sergio; Gullier, Francois; Lyne, Rachel; Rutherford, Kim; Smith, Richard; Micklem, Gos] Cambridge Syst Biol Ctr, Cambridge CB2 1QR, England.
[Morris, Mitzi; Rhrissorrakrai, Kahn; Gutwein, Michelle; Khurana, Ekta; Mangone, Marco; Mecenas, Desirea; Scheid, Paul; Gunsalus, Kristin C.; Piano, Fabio] NYU, Dept Biol, Ctr Genom & Syst Biol, New York, NY 10003 USA.
[Vielle, Anne; Cheung, Ming-Sin; Kolasinska-Zwierz, Paulina; Latorre, Isabel; Ahringer, Julie] Univ Cambridge, Wellcome Trust Canc Res UK Gurdon Inst, Cambridge CB2 1QN, England.
[Niu, Wei; Euskirchen, Ghia; Zhong, Mei; Snyder, Michael] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06824 USA.
[Niu, Wei; Janette, Judith; Wang, Guilin; Reinke, Valerie] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA.
Univ Calif Santa Cruz, Dept Biomol Engn, Santa Cruz, CA 95064 USA.
[Dannenberg, Luke O.; Holster, Heather; Iniguez, A. Leo; Rosenbaum, Heidi] Roche NimbleGen, Madison, WI 53719 USA.
[Dernburg, Abby F.; Dose, Andrea C.; Pham, Hoang] Univ Calif Berkeley, Howard Hughes Med Inst, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
[Dernburg, Abby F.; Dose, Andrea C.; Pham, Hoang] Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA 94720 USA.
[Desai, Arshad; Gassmann, Reto; Muroyama, Andrew; Voronina, Ksenia] Univ Calif San Diego, Ludwig Inst Canc Res, Dept Cellular & Mol Med, San Diego, CA 92093 USA.
[Ewing, Brent; Green, Phil; Leahey, Amber; MacCoss, Michael; Merrihew, Gennifer; Murray, John I.; Preston, Elicia A.; Vafeados, Dionne; Hillier, LaDeana W.; Waterston, Robert H.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA.
[Feingold, Elise A.; Good, Peter J.; Guyer, Mark S.; Lowdon, Rebecca F.] NHGRI, Div Extramural Res, NIH, Bethesda, MD 20892 USA.
[Feng, Xin] SUNY Stony Brook, Dept Biomed Engn, Stony Brook, NY 11794 USA.
[Han, Ting; Khivansara, Vishal; Kim, John K.] Univ Michigan, Inst Life Sci, Dept Human Genet, Ann Arbor, MI 48109 USA.
[Henikoff, Jorja G.; Ooi, Siew-Loon; Henikoff, Steven] Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA.
[Raetsch, Gunnar; Zeller, Georg] Max Planck Gesell, Friedrich Miescher Lab, D-72076 Tubingen, Germany.
[Hyman, Tony; Sarov, Mihail] Max Planck Inst Mol Cell Biol & Genet, D-01307 Dresden, Germany.
[Miller, David M., III; Spencer, William C.] Vanderbilt Univ, Dept Cell & Dev Biol, Nashville, TN 37232 USA.
[Kato, Masaomi; Slack, Frank J.] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA.
[Henz, Stefan R.] Max Planck Inst Dev Biol, D-72076 Tubingen, Germany.
[Lai, Eric C.] Sloan Kettering Inst, New York, NY 10065 USA.
[Lewis, Suzanna; Stinson, E. O.; Washington, Nicole L.] Lawrence Berkeley Natl Lab, Genom Div, Berkeley, CA 94720 USA.
[Lubling, Yaniv; Segal, Eran] Weizmann Inst Sci, Dept Comp Sci & Appl Math, IL-76100 Rehovot, Israel.
[Mackowiak, Sebastian D.; Rajewsky, Nikolaus] Max Delbruck Ctr Mol Med, Div Syst Biol, D-13125 Berlin, Germany.
[Mckay, Sheldon; Stein, Lincoln] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11542 USA.
[Slightam, Cindie; Wu, Beijing; Kim, Stuart K.] Stanford Univ, Med Ctr, Dept Dev Biol, Stanford, CA 94305 USA.
[Zeller, Georg] European Mol Biol Lab, D-69117 Heidelberg, Germany.
[Gunsalus, Kristin C.; Piano, Fabio] NYU, Abu Dhabi, U Arab Emirates.
[Dick, Lindsay] Rockefeller Univ, David Rockefeller Grad Program, New York, NY 10065 USA.
RP Gerstein, MB (reprint author), Yale Univ, Program Computat Biol & Bioinformat, Bass 432,266 Whitney Ave, New Haven, CT 06520 USA.
EM modencode.worm.pi@gersteinlab.org
RI Spencer, William/E-8529-2010; yu, yan/C-2322-2012; Khurana,
Ekta/C-4933-2013; Yan, Koon-Kiu/A-5940-2009; NUI, WEI/B-8300-2011;
Gassmann, Reto/M-6488-2013; Zeller, Georg/M-6484-2013; Hyman,
Anthony/B-3917-2017; Alexander, Roger/A-8643-2008; Liu, Tao/G-3585-2010;
Sboner, Andrea/C-6487-2008;
OI Rutherford, Kim/0000-0001-6277-726X; Micklem, Gos/0000-0002-6883-6168;
Lewis, Suzanna/0000-0002-8343-612X; Liu, Tao/0000-0003-0446-9001; Lloyd,
Paul/0000-0003-3508-5553; Segal, Eran/0000-0002-6859-1164; Hinrichs,
Angie/0000-0002-1697-1130; Slack, Frank/0000-0001-8263-0409; Rozowsky,
Joel/0000-0002-3565-0762; Dernburg, Abby/0000-0001-8037-1079; Mangone,
Marco/0000-0001-7551-8793; Latorre, Isabel/0000-0003-0638-1783;
Gassmann, Reto/0000-0002-0360-2977; Zeller, Georg/0000-0003-1429-7485;
Hyman, Anthony/0000-0003-3664-154X; Alexander,
Roger/0000-0002-2967-7395; Liu, Tao/0000-0002-8818-8313; Sboner,
Andrea/0000-0001-6915-3070; McKay, Sheldon/0000-0002-4011-3160
FU NHGRI of the NIH [R01GM088565]; Muscular Dystrophy Association; Pew
Charitable Trusts; Helmholtz-Alliance on Systems Biology (Max Delbruck
Centrum Systems Biology Network); Wellcome Trust; William H. Gates III
Endowed Chair of Biomedical Sciences
FX Funding for this work came from the NHGRI of the NIH as part of the
modENCODE project, NIH (grant R01GM088565), Muscular Dystrophy
Association, and the Pew Charitable Trusts (J.K.K.); the
Helmholtz-Alliance on Systems Biology (Max Delbruck Centrum Systems
Biology Network) (S.D.M.); the Wellcome Trust (J.A.); the William H.
Gates III Endowed Chair of Biomedical Sciences (R.H.W.); and the A. L.
Williams Professorship (M.B.G.). M. Snyder has an advisory role with
DNANexus, a DNA sequence storage and analysis company. Transfer of
GFP-tagged fosmids requires a Materials Transfer Agreement with the Max
Planck Institute of Molecular Cell Biology and Genetics. Raw microarray
data are available from the Gene Expression Omnibus archive, and raw
sequencing data are available from the SRA archive (accessions are in
table S18). We appreciate help from S. Anthony, K. Bell, C. Davis, C.
Dieterich, Y. Field, A. S. Hammonds, J. Jo, N. Kaplan, A. Manrai, B.
Mathey-Prevot, R. McWhirter, S. Mohr, S. Von Stetina, J. Watson, K.
Watkins, C. Xue, and Y. Zhang, and B. Carpenter. We thank C. Jan and D.
Bartel for sharing data on poly(A) sites before publication, WormBase
curator G. Williams for assistance in quality checking and preparing the
transcriptomics data sets for publication, as well as his fellow curator
P. Davis for reviewing and hand-checking the list of pseudogenes.
NR 76
TC 458
Z9 462
U1 6
U2 90
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
EI 1095-9203
J9 SCIENCE
JI Science
PD DEC 23
PY 2010
VL 330
IS 6012
BP 1775
EP 1787
DI 10.1126/science.1196914
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 698OS
UT WOS:000285603700031
PM 21177976
ER
PT J
AU Roy, S
Ernst, J
Kharchenko, PV
Kheradpour, P
Negre, N
Eaton, ML
Landolin, JM
Bristow, CA
Ma, LJ
Lin, MF
Washietl, S
Arshinoff, BI
Ay, F
Meyer, PE
Robine, N
Washington, NL
Di Stefano, L
Berezikov, E
Brown, CD
Candeias, R
Carlson, JW
Carr, A
Jungreis, I
Marbach, D
Sealfon, R
Tolstorukov, MY
Will, S
Alekseyenko, AA
Artieri, C
Booth, BW
Brooks, AN
Dai, Q
Davis, CA
Duff, MO
Feng, X
Gorchakov, AA
Gu, TT
Henikoff, JG
Kapranov, P
Li, RH
MacAlpine, HK
Malone, J
Minoda, A
Nordman, J
Okamura, K
Perry, M
Powell, SK
Riddle, NC
Sakai, A
Samsonova, A
Sandler, JE
Schwartz, YB
Sher, N
Spokony, R
Sturgill, D
van Baren, M
Wan, KH
Yang, L
Yu, C
Feingold, E
Good, P
Guyer, M
Lowdon, R
Ahmad, K
Andrews, J
Berger, B
Brenner, SE
Brent, MR
Cherbas, L
Elgin, SCR
Gingeras, TR
Grossman, R
Hoskins, RA
Kaufman, TC
Kent, W
Kuroda, MI
Orr-Weaver, T
Perrimon, N
Pirrotta, V
Posakony, JW
Ren, B
Russell, S
Cherbas, P
Graveley, BR
Lewis, S
Micklem, G
Oliver, B
Park, PJ
Celniker, SE
Henikoff, S
Karpen, GH
Lai, EC
MacAlpine, DM
Stein, LD
White, KP
Kellis, M
AF Roy, Sushmita
Ernst, Jason
Kharchenko, Peter V.
Kheradpour, Pouya
Negre, Nicolas
Eaton, Matthew L.
Landolin, Jane M.
Bristow, Christopher A.
Ma, Lijia
Lin, Michael F.
Washietl, Stefan
Arshinoff, Bradley I.
Ay, Ferhat
Meyer, Patrick E.
Robine, Nicolas
Washington, Nicole L.
Di Stefano, Luisa
Berezikov, Eugene
Brown, Christopher D.
Candeias, Rogerio
Carlson, Joseph W.
Carr, Adrian
Jungreis, Irwin
Marbach, Daniel
Sealfon, Rachel
Tolstorukov, Michael Y.
Will, Sebastian
Alekseyenko, Artyom A.
Artieri, Carlo
Booth, Benjamin W.
Brooks, Angela N.
Dai, Qi
Davis, Carrie A.
Duff, Michael O.
Feng, Xin
Gorchakov, Andrey A.
Gu, Tingting
Henikoff, Jorja G.
Kapranov, Philipp
Li, Renhua
MacAlpine, Heather K.
Malone, John
Minoda, Aki
Nordman, Jared
Okamura, Katsutomo
Perry, Marc
Powell, Sara K.
Riddle, Nicole C.
Sakai, Akiko
Samsonova, Anastasia
Sandler, Jeremy E.
Schwartz, Yuri B.
Sher, Noa
Spokony, Rebecca
Sturgill, David
van Baren, Marijke
Wan, Kenneth H.
Yang, Li
Yu, Charles
Feingold, Elise
Good, Peter
Guyer, Mark
Lowdon, Rebecca
Ahmad, Kami
Andrews, Justen
Berger, Bonnie
Brenner, Steven E.
Brent, Michael R.
Cherbas, Lucy
Elgin, Sarah C. R.
Gingeras, Thomas R.
Grossman, Robert
Hoskins, Roger A.
Kaufman, Thomas C.
Kent, William
Kuroda, Mitzi I.
Orr-Weaver, Terry
Perrimon, Norbert
Pirrotta, Vincenzo
Posakony, James W.
Ren, Bing
Russell, Steven
Cherbas, Peter
Graveley, Brenton R.
Lewis, Suzanna
Micklem, Gos
Oliver, Brian
Park, Peter J.
Celniker, Susan E.
Henikoff, Steven
Karpen, Gary H.
Lai, Eric C.
MacAlpine, David M.
Stein, Lincoln D.
White, Kevin P.
Kellis, Manolis
CA modENCODE Consortium
TI Identification of Functional Elements and Regulatory Circuits by
Drosophila modENCODE
SO SCIENCE
LA English
DT Article
ID PREDICTIVE CHROMATIN SIGNATURES; TRANSCRIPTION FACTORS; SOMATIC-CELLS;
HUMAN GENOME; DNA-BINDING; RNA PATHWAY; MELANOGASTER; SEQUENCE; REGIONS;
NETWORK
AB To gain insight into how genomic information is translated into cellular and developmental programs, the Drosophila model organism Encyclopedia of DNA Elements (modENCODE) project is comprehensively mapping transcripts, histone modifications, chromosomal proteins, transcription factors, replication proteins and intermediates, and nucleosome properties across a developmental time course and in multiple cell lines. We have generated more than 700 data sets and discovered protein-coding, noncoding, RNA regulatory, replication, and chromatin elements, more than tripling the annotated portion of the Drosophila genome. Correlated activity patterns of these elements reveal a functional regulatory network, which predicts putative new functions for genes, reveals stage-and tissue-specific regulators, and enables gene-expression prediction. Our results provide a foundation for directed experimental and computational studies in Drosophila and related species and also a model for systematic data integration toward comprehensive genomic and functional annotation.
C1 [Roy, Sushmita; Ernst, Jason; Kheradpour, Pouya; Bristow, Christopher A.; Lin, Michael F.; Washietl, Stefan; Ay, Ferhat; Meyer, Patrick E.; Di Stefano, Luisa; Candeias, Rogerio; Jungreis, Irwin; Marbach, Daniel; Sealfon, Rachel; Will, Sebastian; Berger, Bonnie; Kellis, Manolis] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA.
[Roy, Sushmita; Ernst, Jason; Kheradpour, Pouya; Bristow, Christopher A.; Lin, Michael F.; Jungreis, Irwin; Marbach, Daniel; Sealfon, Rachel; Berger, Bonnie; Kellis, Manolis] MIT, Broad Inst, Cambridge, MA 02140 USA.
[Roy, Sushmita; Ernst, Jason; Kheradpour, Pouya; Bristow, Christopher A.; Lin, Michael F.; Jungreis, Irwin; Marbach, Daniel; Sealfon, Rachel; Berger, Bonnie; Kellis, Manolis] Harvard Univ, Cambridge, MA 02140 USA.
[Kharchenko, Peter V.; Tolstorukov, Michael Y.; Schwartz, Yuri B.; Park, Peter J.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA.
[Negre, Nicolas; Ma, Lijia; Brown, Christopher D.; Spokony, Rebecca; Grossman, Robert; White, Kevin P.] Univ Chicago, Inst Genom & Syst Biol, Dept Human Genet, Chicago, IL 60637 USA.
[Eaton, Matthew L.; MacAlpine, Heather K.; Powell, Sara K.; MacAlpine, David M.] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA.
[Landolin, Jane M.; Carlson, Joseph W.; Booth, Benjamin W.; Minoda, Aki; Sandler, Jeremy E.; Wan, Kenneth H.; Yu, Charles; Hoskins, Roger A.; Celniker, Susan E.; Karpen, Gary H.] Lawrence Berkeley Natl Lab, Dept Genome Dynam, Berkeley, CA 94720 USA.
[Arshinoff, Bradley I.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A1, Canada.
[Robine, Nicolas; Dai, Qi; Henikoff, Jorja G.; Okamura, Katsutomo; Lai, Eric C.] Sloan Kettering Inst, New York, NY 10065 USA.
[Washington, Nicole L.; Lewis, Suzanna] LBNL, Genome Sci Div, Berkeley, CA 94720 USA.
[Carr, Adrian; Russell, Steven; Micklem, Gos] Univ Cambridge, Dept Genet, Cambridge CB2 3EH, England.
[Carr, Adrian; Russell, Steven; Micklem, Gos] Univ Cambridge, Cambridge Syst Biol Ctr, Cambridge CB2 3EH, England.
[Alekseyenko, Artyom A.; Gorchakov, Andrey A.; Kuroda, Mitzi I.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA.
[Alekseyenko, Artyom A.; Gorchakov, Andrey A.; Kuroda, Mitzi I.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Artieri, Carlo; Malone, John; Sturgill, David; Oliver, Brian] NIDDK, Sect Dev Genom, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA.
[Davis, Carrie A.; Feng, Xin; Gingeras, Thomas R.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
[Duff, Michael O.; Yang, Li; Graveley, Brenton R.] Univ Connecticut, Stem Cell Inst, Dept Genet & Dev Biol, Farmington, CT 06030 USA.
[Gu, Tingting; Riddle, Nicole C.; Elgin, Sarah C. R.] Washington Univ, Dept Biol, St Louis, MO 63130 USA.
[Kapranov, Philipp; Gingeras, Thomas R.] Affymetrix, Santa Clara, CA 95051 USA.
[Li, Renhua; Feingold, Elise; Good, Peter; Guyer, Mark; Lowdon, Rebecca] NHGRI, Div Extramural Res, NIH, Bethesda, MD 20892 USA.
[Arshinoff, Bradley I.; Feng, Xin; Perry, Marc; Stein, Lincoln D.] Ontario Inst Canc Res, Toronto, ON M5G 0A3, Canada.
[Samsonova, Anastasia; Perrimon, Norbert] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Samsonova, Anastasia; Perrimon, Norbert] Harvard Univ, Sch Med, Drosophila RNAi Screening Ctr, Boston, MA 02115 USA.
[van Baren, Marijke; Brent, Michael R.] Washington Univ, Ctr Genome Sci, St Louis, MO 63108 USA.
[Andrews, Justen; Cherbas, Lucy; Kaufman, Thomas C.; Cherbas, Peter] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA.
[Nordman, Jared; Sher, Noa; Orr-Weaver, Terry] Whitehead Inst, Cambridge, MA 02142 USA.
[Berezikov, Eugene] Royal Netherlands Acad Arts & Sci, Hubrecht Inst, Utrecht, Netherlands.
[Berezikov, Eugene] Univ Med Ctr Utrecht, Utrecht, Netherlands.
[Cherbas, Lucy; Cherbas, Peter] Indiana Univ, Ctr Genom & Bioinformat, Bloomington, IN 47405 USA.
[Henikoff, Steven] Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA.
[Posakony, James W.; Ren, Bing] Univ Calif San Diego, Sect Cell & Dev Biol, Div Biol Sci, La Jolla, CA 92093 USA.
[Pirrotta, Vincenzo] Rutgers State Univ, Dept Mol Biol & Biochem, Piscataway, NJ 08854 USA.
[Brooks, Angela N.; Brenner, Steven E.; Karpen, Gary H.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
[Sakai, Akiko; Ahmad, Kami] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Meyer, Patrick E.] Univ Libre Brussels, Machine Learning Grp, B-1050 Brussels, Belgium.
[Di Stefano, Luisa] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.
[Brenner, Steven E.] Univ Calif Berkeley, Dept Plant & Microbial Biol, Berkeley, CA 94720 USA.
[Ay, Ferhat] Univ Florida, Gainesville, FL 32611 USA.
[Kent, William] Univ Calif Santa Cruz, Sch Engn, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA.
[Kent, William] Univ Calif Santa Cruz, Howard Hughes Med Inst, Santa Cruz, CA 95064 USA.
[Feng, Xin] SUNY Stony Brook, Dept Biomed Engn, Stony Brook, NY 11794 USA.
RP Kellis, M (reprint author), MIT, Comp Sci & Artificial Intelligence Lab, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM celniker@fruitfly.org; steveh@fhcrc.org; karpen@fruitfly.org;
laie@mskcc.org; david.macalpine@duke.edu; lincoln.stein@gmail.com;
kpwhite@uchicago.edu; manoli@mit.edu
RI Samsonova, Anastasia/Q-7591-2016; Minoda, Aki/D-5335-2017; Sakai,
Akiko/A-8929-2010; Berezikov, Eugene/D-3363-2013; Brenner,
Steven/A-8729-2008; Venken, Koen/B-9909-2013; Gorchakov,
Andrey/N-5840-2015; Eaton, Matthew/C-4408-2011; jiang,
lichun/F-3776-2012; White, Rob/G-4835-2012; Russell, Steve/A-4072-2011;
Brooks, Angela/B-6173-2011; Graveley, Brenton/C-3108-2013; Hansen,
Kasper/E-6094-2011
OI Meyer, Folker/0000-0003-1112-2284; Lloyd, Paul/0000-0003-3508-5553;
Bellen, Hugo/0000-0001-5992-5989; Hinrichs, Angie/0000-0002-1697-1130;
Negre, Nicolas/0000-0001-9727-3416; Robine, Nicolas/0000-0001-5698-8183;
Brown, Christopher/0000-0002-3785-5008; Samsonova,
Anastasia/0000-0002-9353-9173; Minoda, Aki/0000-0002-2927-5791;
Gingeras, Thomas/0000-0001-9106-3573; Washington,
Nicole/0000-0001-8936-9143; Grossman, Robert/0000-0003-3741-5739;
Graveley, Brenton/0000-0001-5777-5892; Rutherford,
Kim/0000-0001-6277-726X; McKay, Sheldon/0000-0002-4011-3160; Micklem,
Gos/0000-0002-6883-6168; Lewis, Suzanna/0000-0002-8343-612X; Berezikov,
Eugene/0000-0002-1145-2884; Brenner, Steven/0000-0001-7559-6185; Venken,
Koen/0000-0003-0741-4698; Gorchakov, Andrey/0000-0003-2830-4236; jiang,
lichun/0000-0003-2462-7636; Russell, Steve/0000-0003-0546-3031; Hansen,
Kasper/0000-0003-0086-0687
FU National Human Genome Research Institute [RC2HG005639, U01HG004271,
U01HG004258, U01HG004264, U01HG004279, U01HG004261, U01HG004274,
U41HG004269]; LBNL [DE-AC02-05CH11231]; NSF [0937060, 0905968, 0644282];
Natural Sciences and Engineering Research Council of Canada (NSERC);
Japan Society for the Promotion of Science; Swedish Research Council;
NIH National Research Service; National Defense Science and Engineering;
Austrian Fonds zur Forderung der wissenschaftlichen Forschung; Leukemia
and Lymphoma Society; Lilly-Life Sciences Research Foundation;
Affymetrix; Swiss National Science Foundation; German Research
Foundation [WI 3628/1-1]; HHMI; Indiana Genomics Initiative; NIDDK
genomics core laboratory; NIH [R01HG004037]; Sloan Foundation
FX This work was supported by the National Human Genome Research Institute
as part of the modENCODE project under RC2HG005639 (M.K.), U01HG004271
(S.E.C.), U01HG004258 (G.H.K.), U01HG004264 (K.P.W.), U01HG004279
(D.M.M.), U01HG004261 (E.L.), U01HG004274 (S.H.), and U41HG004269
(L.S.). Awards to S.E.C. and G.H.K. were carried out at LBNL under
contract no. DE-AC02-05CH11231. Additional support was provided by the
NSF under grant 0937060 to the Computing Research Association for the
CIFellows Project (S.R.) and under award no. 0905968 (J.E.), a Natural
Sciences and Engineering Research Council of Canada (NSERC) fellowship
(B.A.), T. Kahveci (F.A.), the Japan Society for the Promotion of
Science (K.O.), the Swedish Research Council (Q.D.), a NIH National
Research Service Award postdoctoral fellowship (C.A.B.), a National
Defense Science and Engineering Graduate Fellowship (R.S.), an Erwin
Schrodinger Fellowship of the Austrian Fonds zur Forderung der
wissenschaftlichen Forschung (S.W.), a Leukemia and Lymphoma Society
fellowship (S.W.), a Lilly-Life Sciences Research Foundation fellowship
(C.D.B.), a NSERC postdoctoral fellowship (C. G. A.), Affymetrix
(T.G.R.), a fellowship from the Swiss National Science Foundation
(D.M.), a German Research Foundation grant WI 3628/1-1 (S.W.), a HHMI
Damon Runyon Cancer Research fellowship (J.T.N.), the Indiana Genomics
Initiative (T.C.K.), H. Smith and the NIDDK genomics core laboratory
(B.O.), NIH R01HG004037, NSF CAREER award 0644282, and the Sloan
Foundation (M.K.). A full list of author contributions is available in
the SOM.
NR 69
TC 524
Z9 531
U1 17
U2 82
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 DEC 23
PY 2010
VL 330
IS 6012
BP 1787
EP 1797
DI 10.1126/science.1198374
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 698OS
UT WOS:000285603700032
ER
PT J
AU Johnson, RC
Nelson, GW
Troyer, JL
Lautenberger, JA
Kessing, BD
Winkler, CA
O'Brien, SJ
AF Johnson, Randall C.
Nelson, George W.
Troyer, Jennifer L.
Lautenberger, James A.
Kessing, Bailey D.
Winkler, Cheryl A.
O'Brien, Stephen J.
TI Accounting for multiple comparisons in a genome-wide association study
(GWAS)
SO BMC GENOMICS
LA English
DT Article
ID SINGLE-NUCLEOTIDE POLYMORPHISMS; LINKAGE DISEQUILIBRIUM;
PRINCIPAL-COMPONENTS; GENETIC ASSOCIATION; HAPLOTYPE BLOCKS;
RECOMBINATION; HISTORY; MAP; LD
AB Background: As we enter an era when testing millions of SNPs in a single gene association study will become the standard, consideration of multiple comparisons is an essential part of determining statistical significance. Bonferroni adjustments can be made but are conservative due to the preponderance of linkage disequilibrium (LD) between genetic markers, and permutation testing is not always a viable option. Three major classes of corrections have been proposed to correct the dependent nature of genetic data in Bonferroni adjustments: permutation testing and related alternatives, principal components analysis (PCA), and analysis of blocks of LD across the genome. We consider seven implementations of these commonly used methods using data from 1514 European American participants genotyped for 700,078 SNPs in a GWAS for AIDS.
Results: A Bonferroni correction using the number of LD blocks found by the three algorithms implemented by Haploview resulted in an insufficiently conservative threshold, corresponding to a genome-wide significance level of alpha = 0.15 0.20. We observed a moderate increase in power when using PRESTO, SLIDE, and simpleM when compared with traditional Bonferroni methods for population data genotyped on the Affymetrix 6.0 platform in European Americans (alpha = 0.05 thresholds between 1 x 10(-7) and 7 x 10(-8)).
Conclusions: Correcting for the number of LD blocks resulted in an anti-conservative Bonferroni adjustment. SLIDE and simpleM are particularly useful when using a statistical test not handled in optimized permutation testing packages, and genome-wide corrected p-values using SLIDE, are much easier to interpret for consumers of GWAS studies.
C1 [Lautenberger, James A.; O'Brien, Stephen J.] NCI, Lab Genom Divers, Frederick, MD 21701 USA.
[Johnson, Randall C.; Nelson, George W.; Troyer, Jennifer L.; Kessing, Bailey D.; Winkler, Cheryl A.] NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Johnson, Randall C.] Conservatoire Natl Arts & Metiers, Chaire Bioinformat, F-75003 Paris, France.
RP O'Brien, SJ (reprint author), NCI, Lab Genom Divers, Frederick, MD 21701 USA.
EM obrien@ncifcrf.gov
RI Troyer, Jennifer/B-8415-2012; Johnson, Randall/B-1517-2014
OI Johnson, Randall/0000-0001-7754-0847
FU NationalCancer Institute, National Institutes of Health
[HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer
Research
FX 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. We thank the individuals who
participated in the HGDS, MACS, MHCS, and SFCC cohort studies, as well
as the physicians and researchers responsible for recruitment and sample
collection. We also thank Michelle Hall, Michael Malasky, Lisa Maslan,
Mary McNally, and Jami Troxler who performed the genotyping, Leslie
Chinn, Sher Hendrickson, Carl Mclntosh, and Joan Pontius who helped with
quality control and annotation of the GWAS data, and Julie Johnson for
her comments and discussion. This project has been funded in whole or in
part with federal funds from the NationalCancer Institute, National
Institutes of Health, under contract HHSN261200800001E. The content of
this publication does not necessarily reflect the views or policies of
the Department of Health and Human Services, nor does mention of trade
names, commercial products, or organizations imply endorsement by the US
Government. This research was supported [in part] by the Intramural
Research Program of NIH, National Cancer Institute, Center for Cancer
Research.
NR 32
TC 63
Z9 65
U1 0
U2 20
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD DEC 22
PY 2010
VL 11
AR 724
DI 10.1186/1471-2164-11-724
PG 6
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 709FU
UT WOS:000286424100001
PM 21176216
ER
PT J
AU Urzua, U
Owens, GA
Zhang, GM
Cherry, JM
Sharp, JJ
Munroe, DJ
AF Urzua, Ulises
Owens, Garrison A.
Zhang, Gen-Mu
Cherry, James M.
Sharp, John J.
Munroe, David J.
TI Tumor and reproductive traits are linked by RNA metabolism genes in the
mouse ovary: a transcriptome-phenotype association analysis
SO BMC GENOMICS
LA English
DT Article; Proceedings Paper
CT 5th International Conference of the
Brazilian-Association-for-Bioinformatics-and-Computational-Biology
CY OCT 18-22, 2009
CL Angra dos Reis, BRAZIL
SP Brazilian Assoc Bioinformat & Computational Biol
ID GRANULOSA-CELLS; FOLLICLE DEVELOPMENT; CDNA MICROARRAY; MURINE MODEL;
EXPRESSION; CANCER; OVULATION; PATHWAY; PHOSPHORYLATION; IDENTIFICATION
AB Background: The link between reproductive life history and incidence of ovarian tumors is well known. Periods of reduced ovulations may confer protection against ovarian cancer. Using phenotypic data available for mouse, a possible association between the ovarian transcriptome, reproductive records and spontaneous ovarian tumor rates was investigated in four mouse inbred strains. NIA15k-DNA microarrays were employed to obtain expression profiles of BalbC, C57BL6, FVB and SWR adult ovaries.
Results: Linear regression analysis with multiple-test control (adjusted p <= 0.05) resulted in ovarian tumor frequency (OTF) and number of litters (NL) as the top-correlated among five tested phenotypes. Moreover, nearly one-hundred genes were coincident between these two traits and were decomposed in 76 OTF(-) NL(+) and 20 OTF(+) NL(-) genes, where the plus/minus signs indicate the direction of correlation. Enriched functional categories were RNA-binding/mRNA-processing and protein folding in the OTF(-) NL(+) and the OTF(+) NL(-) subsets, respectively. In contrast, no associations were detected between OTF and litter size (LS), the latter a measure of ovulation events in a single estrous cycle.
Conclusion: Literature text-mining pointed to post-transcriptional control of ovarian processes including oocyte maturation, folliculogenesis and angiogenesis as possible causal relationships of observed tumor and reproductive phenotypes. We speculate that repetitive cycling instead of repetitive ovulations represent the actual link between ovarian tumorigenesis and reproductive records.
C1 [Urzua, Ulises] Univ Chile, ICBM, Lab Genom Aplicada, Santiago, Chile.
[Owens, Garrison A.; Cherry, James M.; Munroe, David J.] SAIC NCI Frederick, Lab Mol Technol, Frederick, MD 21701 USA.
[Zhang, Gen-Mu] SAIC NCI Frederick, Lab Anim Sci Program, Frederick, MD 21702 USA.
[Sharp, John J.] Baylor Coll Med, Ctr Comparat Med, Houston, TX 77030 USA.
RP Urzua, U (reprint author), Univ Chile, ICBM, Lab Genom Aplicada, Independencia 1027, Santiago, Chile.
EM uurzua@med.uchile.cl
RI Urzua, Ulises/A-3982-2013;
OI Urzua, Ulises/0000-0003-0522-5754
FU PHS HHS [N01-C0-12400]
NR 53
TC 2
Z9 2
U1 1
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD DEC 22
PY 2010
VL 11
SU 5
AR S1
DI 10.1186/1471-2164-11-S5-S1
PG 11
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 729AA
UT WOS:000287915800001
PM 21210965
ER
PT J
AU Hanover, JA
AF Hanover, John A.
TI Epigenetics Gets Sweeter: O-GlcNAc Joins the "Histone Code"
SO CHEMISTRY & BIOLOGY
LA English
DT Editorial Material
ID TETRATRICOPEPTIDE REPEATS; N-ACETYLGLUCOSAMINE; TRANSFERASE;
GLYCOSYLATION; CHROMATIN; PROTEINS; GENE
AB O-GlcNAcylation has now been added to the growing list of histone modifications making up the multifaceted "histone-code" (Sakabe et al., 2010). The sites of O-GlcNAc-histone modification hint at a role in chromatin remodeling, thus adding to mounting evidence that O-GlcNAc cycling sits atop a robust regulatory network maintaining higher-order chromatin structure and epigenetic memory.
C1 NIDDK, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Hanover, JA (reprint author), NIDDK, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM jah@helix.nih.gov
FU Intramural NIH HHS [ZIA DK060103-04]
NR 12
TC 21
Z9 21
U1 0
U2 7
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-5521
J9 CHEM BIOL
JI Chem. Biol.
PD DEC 22
PY 2010
VL 17
IS 12
BP 1272
EP 1274
DI 10.1016/j.chembiol.2010.12.001
PG 3
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 717BA
UT WOS:000287016000004
PM 21168762
ER
PT J
AU Mathews, JM
Watson, SL
Snyder, RW
Burgess, JP
Morgan, DL
AF Mathews, James M.
Watson, Scott L.
Snyder, Rodney W.
Burgess, Jason P.
Morgan, Daniel L.
TI Reaction of the Butter Flavorant Diacetyl (2,3-Butanedione) with
N-alpha-Acetylarginine: A Model for Epitope Formation with Pulmonary
Proteins in the Etiology of Obliterative Bronchiolitis
SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
LA English
DT Article
DE Diacetyl; 2,3-butanedione; artificial butter flavoring; arginine
adducts; toxicity
ID PERFORMANCE LIQUID-CHROMATOGRAPHY; ARGININE; WORKERS; LUNG
AB The butter flavorant diacetyl (2,3-butanedione) is implicated in causing obliterative bronchiolitis in microwave popcorn plant workers. Because diacetyl modifies arginine residues, an immunological basis for its toxicity is under investigation. Reaction products of diacetyl with N-alpha-acetylarginine (AcArg) were determined as a model for hapten formation, with characterization by mass spectrometry, NMR, and HPLC with UV detection and radiodetection. Four products were identified by LC-MS, each with a positive ion of m/z 303 (diacetyl + AcArg); one pair displayed an additional ion at m/z 217 (AcArg), the other pair at m/z 285 (- H(2)O). Their (1)H-(13)C NMR correlation spectra were consistent with the addition of one or two of the guanidine nitrogens to form aminols. Open-chain pairs interconverted at pH 2, as did the cyclized, but all four interconverted at neutral pH. This is the first structural characterization of the covalent adducts between diacetyl and an arginine moiety.
C1 [Mathews, James M.; Watson, Scott L.; Snyder, Rodney W.; Burgess, Jason P.] RTI Int, Res Triangle Pk, NC 27709 USA.
[Morgan, Daniel L.] NIEHS, Res Triangle Pk, NC 27709 USA.
RP Mathews, JM (reprint author), RTI Int, POB 12194, Res Triangle Pk, NC 27709 USA.
EM mathews@rti.org
FU Intramural NIH HHS [ZIA ES101865-06]; NIEHS NIH HHS [N01ES75563]; PHS
HHS [HHSN29120077563]
NR 25
TC 18
Z9 18
U1 0
U2 10
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0021-8561
J9 J AGR FOOD CHEM
JI J. Agric. Food Chem.
PD DEC 22
PY 2010
VL 58
IS 24
BP 12761
EP 12768
DI 10.1021/jf103251w
PG 8
WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science &
Technology
SC Agriculture; Chemistry; Food Science & Technology
GA 693PQ
UT WOS:000285236400027
PM 21077678
ER
PT J
AU Sosa, MS
Lopez-Haber, C
Yang, CF
Wang, HB
Lemmon, MA
Busillo, JM
Luo, JS
Benovic, JL
Klein-Szanto, A
Yagi, H
Gutkind, JS
Parsons, RE
Kazanietz, MG
AF Sosa, Maria Soledad
Lopez-Haber, Cynthia
Yang, Chengfeng
Wang, HongBin
Lemmon, Mark A.
Busillo, John M.
Luo, Jiansong
Benovic, Jeffrey L.
Klein-Szanto, Andres
Yagi, Hiroshi
Gutkind, J. Silvio
Parsons, Ramon E.
Kazanietz, Marcelo G.
TI Identification of the Rac-GEF P-Rex1 as an Essential Mediator of ErbB
Signaling in Breast Cancer
SO MOLECULAR CELL
LA English
DT Article
ID COMPARATIVE GENOMIC HYBRIDIZATION; NUCLEOTIDE EXCHANGE FACTOR;
GROWTH-FACTOR RECEPTOR; INDUCED CELL MOTILITY; BETA-GAMMA-SUBUNITS;
CYCLIN D1; NEUTROPHIL FUNCTION; EPITHELIAL-CELLS; UP-REGULATION; RHO
GTPASES
AB While the small GTPase Rac1 and its effectors are well-established mediators of mitogenic and motile signaling by tyrosine kinase receptors and have been implicated in breast tumorigenesis, little is known regarding the exchange factors (Rac-GEFs) that mediate ErbB receptor responses. Here, we identify the PIP(3)-G beta gamma-dependent Rac-GEF P-Rex1 as an essential mediator of Rac1 activation, motility, cell growth, and tumorigenesis driven by ErbB receptors in breast cancer cells. Notably, activation of P-Rex1 in breast cancer cells requires the convergence of inputs from ErbB receptors and a G beta gamma- and PI3K gamma-dependent pathway. Moreover, we identified the GPCR CXCR4 as a crucial mediator of P-Rex1/Rac1 activation in response to ErbB ligands. P-Rex1 is highly overexpressed in human breast cancers and their derived cell lines, particularly those with high ErbB2 and ER expression. In addition to the prognostic and therapeutic implications, our findings reveal an ErbB effector pathway that is crucial for breast cancer progression.
C1 [Sosa, Maria Soledad; Lopez-Haber, Cynthia; Wang, HongBin; Kazanietz, Marcelo G.] Univ Penn, Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA.
[Lemmon, Mark A.] Univ Penn, Sch Med, Dept Biochem & Biophys, Philadelphia, PA 19104 USA.
[Yang, Chengfeng] Michigan State Univ, Ctr Integrat Toxicol, E Lansing, MI 48824 USA.
[Busillo, John M.; Luo, Jiansong; Benovic, Jeffrey L.] Thomas Jefferson Univ, Dept Biochem & Mol Biol, Philadelphia, PA 19107 USA.
[Klein-Szanto, Andres] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[Yagi, Hiroshi; Gutkind, J. Silvio] NIDCR, Oral & Pharyngeal Canc Branch, Bethesda, MD 20892 USA.
[Parsons, Ramon E.] Columbia Univ, Med Ctr, Inst Canc Genet, New York, NY 10032 USA.
RP Kazanietz, MG (reprint author), Univ Penn, Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA.
EM marcelog@upenn.edu
RI wang, hongbin/E-5541-2011; Gutkind, J. Silvio/A-1053-2009;
OI Lemmon, Mark/0000-0002-3379-5319
FU NIH [R01CA74197, R01CA129133, R01CA139120]; Susan Komen Foundation
[KG090522]; NIDCR, NIH; [R01CA129626]; [R01CA155117]
FX This work is supported by grants R01CA74197, R01CA129133, and
R01CA139120 (NIH) and KG090522 (Susan Komen Foundation for the Cure) to
M.G.K. and by grant R01CA129626 to J.L.B. H.Y. and J.S.G. are supported
by the Intramural Program, NIDCR, NIH. R.E.P. is supported by grant
R01CA155117. We thank Andy Cucchiara (UPenn) for help with statistical
analyses and Celine Lefebvre (Columbia University) for support with
microarray data analysis.
NR 54
TC 75
Z9 75
U1 0
U2 12
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 DEC 22
PY 2010
VL 40
IS 6
BP 877
EP 892
DI 10.1016/j.molcel.2010.11.029
PG 16
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 701NF
UT WOS:000285823900007
PM 21172654
ER
PT J
AU Tao, RD
Coleman, MC
Pennington, JD
Ozden, O
Park, SH
Jiang, HY
Kim, HS
Flynn, CR
Hill, S
McDonald, WH
Olivier, AK
Spitz, DR
Gius, D
AF Tao, Randa
Coleman, Mitchell C.
Pennington, J. Daniel
Ozden, Ozkan
Park, Seong-Hoon
Jiang, Haiyan
Kim, Hyun-Seok
Flynn, Charles Robb
Hill, Salisha
McDonald, W. Hayes
Olivier, Alicia K.
Spitz, Douglas R.
Gius, David
TI Sirt3-Mediated Deacetylation of Evolutionarily Conserved Lysine 122
Regulates MnSOD Activity in Response to Stress
SO MOLECULAR CELL
LA English
DT Article
ID DEPENDENT DEACETYLASE; SIR2 HOMOLOG; MITOCHONDRIA; CANCER; ACETYLATION;
SUPEROXIDE; CELLS
AB Genetic deletion of the mitochondrial deacetylase sirtuin-3 (Sirt3) results in increased mitochondrial superoxide, a tumor-permissive environment, and mammary tumor development. MnSOD contains a nutrient- and ionizing radiation (lR)-dependent reversible acetyl-lysine that is hyperacetylated in Sirt3(-/-) livers at 3 months of age. Livers of Sirt3(-/-) mice exhibit decreased MnSOD activity, but not immunoreactive protein, relative to wild-type livers. Reintroduction of wild-type but not deacetylation null Sirt3 into Sirt3(-/-) MEFs deacetylated lysine and restored MnSOD activity. Site-directed mutagenesis of MnSOD lysine 122 to an arginine, mimicking deacetylation (lenti-MnSOD(K122-R)), increased MnSOD activity when expressed in MnSOD(-/-) MEFs, suggesting acetylation directly regulates function. Furthermore, infection of Sirt3(-/-) MEFs with lenti-MnSOD(K122-R) inhibited in vitro immortalization by an oncogene (Ras), inhibited IR-induced genomic instability, and decreased mitochondrial superoxide. Finally, IR was unable to induce MnSOD deacetylation or activity in Sirt3(-/-) livers, and these irradiated livers displayed significant IR-induced cell damage and microvacuolization in their hepatocytes.
C1 [Ozden, Ozkan; Park, Seong-Hoon; Jiang, Haiyan; Kim, Hyun-Seok; Gius, David] Vanderbilt Univ, Med Ctr, Dept Radiat Oncol, Nashville, TN 37232 USA.
[Ozden, Ozkan; Park, Seong-Hoon; Jiang, Haiyan; Kim, Hyun-Seok; Gius, David] Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA.
[Tao, Randa; Pennington, J. Daniel] Howard Hughes Med Inst, Bethesda, MD 20892 USA.
[Tao, Randa; Pennington, J. Daniel] NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Coleman, Mitchell C.; Spitz, Douglas R.] Univ Iowa, Holden Comprehens Canc Ctr, Dept Radiat Oncol, Free Rad & Radiat Biol Program, Iowa City, IA 52242 USA.
[Olivier, Alicia K.] Univ Iowa, Carver Coll Med, Dept Pathol, Iowa City, IA 52242 USA.
[Flynn, Charles Robb] Vanderbilt Univ, Dept Surg, Sch Med, Nashville, TN 37232 USA.
[Hill, Salisha; McDonald, W. Hayes] Vanderbilt Univ, Mass Spectrometry Res Ctr, Sch Med, Nashville, TN 37232 USA.
RP Gius, D (reprint author), Vanderbilt Univ, Med Ctr, Dept Radiat Oncol, Nashville, TN 37232 USA.
EM david.gius@vanderbilt.edu
RI Flynn, Charles/M-3895-2015; McDonald, W. Hayes/B-4109-2016
OI Flynn, Charles/0000-0002-3749-0598; McDonald, W.
Hayes/0000-0002-3510-426X
FU NCI [1R01CA152601-01]; DOD [BC093803]; SPORE [P50CA98131]; NIH; DOE
[R01CA133114, T32CA078586, P30CA086862, DE-SC0000830]; [F30AG030839]
FX D.G. is supported by 1R01CA152601-01 from the NCI, BC093803 from the
DOD, and SPORE P50CA98131. D.R.S., A.K.O., and M.C.C. are supported by
grants from the NIH and DOE (R01CA133114, T32CA078586, P30CA086862, and
DE-SC0000830). J.D.P. is supported by F30AG030839. We thank Melissa
Stauffer of Scientific Editing Solutions for editorial assistance.
NR 19
TC 295
Z9 312
U1 2
U2 29
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 DEC 22
PY 2010
VL 40
IS 6
BP 893
EP 904
DI 10.1016/j.molcel.2010.12.013
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 701NF
UT WOS:000285823900008
PM 21172655
ER
PT J
AU Kaptchuk, TJ
Friedlander, E
Kelley, JM
Sanchez, MN
Kokkotou, E
Singer, JP
Kowalczykowski, M
Miller, FG
Kirsch, I
Lembo, AJ
AF Kaptchuk, Ted J.
Friedlander, Elizabeth
Kelley, John M.
Sanchez, M. Norma
Kokkotou, Efi
Singer, Joyce P.
Kowalczykowski, Magda
Miller, Franklin G.
Kirsch, Irving
Lembo, Anthony J.
TI Placebos without Deception: A Randomized Controlled Trial in Irritable
Bowel Syndrome
SO PLOS ONE
LA English
DT Article
ID QUALITY-OF-LIFE; CLINICAL-TRIALS; END-POINT; METAANALYSIS; VALIDATION;
DISORDERS; EFFICACY; BLIND
AB Background: Placebo treatment can significantly influence subjective symptoms. However, it is widely believed that response to placebo requires concealment or deception. We tested whether open-label placebo (non-deceptive and non-concealed administration) is superior to a no-treatment control with matched patient-provider interactions in the treatment of irritable bowel syndrome (IBS).
Methods: Two-group, randomized, controlled three week trial (August 2009-April 2010) conducted at a single academic center, involving 80 primarily female (70%) patients, mean age 47 +/- 18 with IBS diagnosed by Rome III criteria and with a score >= 150 on the IBS Symptom Severity Scale (IBS-SSS). Patients were randomized to either open-label placebo pills presented as "placebo pills made of an inert substance, like sugar pills, that have been shown in clinical studies to produce significant improvement in IBS symptoms through mind-body self-healing processes" or no-treatment controls with the same quality of interaction with providers. The primary outcome was IBS Global Improvement Scale (IBS-GIS). Secondary measures were IBS Symptom Severity Scale (IBS-SSS), IBS Adequate Relief (IBS-AR) and IBS Quality of Life (IBS-QoL).
Findings: Open-label placebo produced significantly higher mean (+/- SD) global improvement scores (IBS-GIS) at both 11-day midpoint (5.2 +/- 1.0 vs. 4.0 +/- 1.1, p<.001) and at 21-day endpoint (5.0 +/- 1.5 vs. 3.9 +/- 1.3, p = .002). Significant results were also observed at both time points for reduced symptom severity (IBS-SSS, p = .008 and p = .03) and adequate relief (IBS-AR, p = .02 and p = .03); and a trend favoring open-label placebo was observed for quality of life (IBS-QoL) at the 21-day endpoint (p = .08).
Conclusion: Placebos administered without deception may be an effective treatment for IBS. Further research is warranted in IBS, and perhaps other conditions, to elucidate whether physicians can benefit patients using placebos consistent with informed consent.
C1 [Kaptchuk, Ted J.; Friedlander, Elizabeth; Sanchez, M. Norma; Kokkotou, Efi; Kowalczykowski, Magda; Lembo, Anthony J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA.
[Kaptchuk, Ted J.; Singer, Joyce P.] Harvard Univ, Sch Med, Osher Res Ctr, Boston, MA 02215 USA.
[Kelley, John M.] Endicott Coll, Dept Psychol, Beverly, MA USA.
[Kelley, John M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02215 USA.
[Miller, Franklin G.] NIH, Dept Bioeth, Bethesda, MD 20892 USA.
[Kirsch, Irving] Univ Hull, Dept Psychol, Kingston Upon Hull HU6 7RX, N Humberside, England.
RP Kaptchuk, TJ (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA.
EM ted_kaptchuk@hms.harvard.edu
FU National Center for Complementary and Alternative Medicine-NIH [K24
AT004095, R01 AT00402-01, R01AT004662]
FX This study was partially supported by grant K24 AT004095, R01 AT00402-01
and R01AT004662 from National Center for Complementary and Alternative
Medicine-NIH and in part from a gift from The Bernard Osher Foundation.
The opinions expressed by the authors are their views alone and do not
reflect the official views or policy of the National Center for
Complementary and Alternative Medicine, National Institutes of Health,
Public Health Service or the U.S. 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 37
TC 196
Z9 197
U1 9
U2 54
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 DEC 22
PY 2010
VL 5
IS 12
AR e15591
DI 10.1371/journal.pone.0015591
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 698FG
UT WOS:000285578000036
PM 21203519
ER
PT J
AU Levkovitz, L
Yosef, N
Gershengorn, MC
Ruppin, E
Sharan, R
Oron, Y
AF Levkovitz, Liron
Yosef, Nir
Gershengorn, Marvin C.
Ruppin, Eytan
Sharan, Roded
Oron, Yoram
TI A Novel HMM-Based Method for Detecting Enriched Transcription Factor
Binding Sites Reveals RUNX3 as a Potential Target in Pancreatic Cancer
Biology
SO PLOS ONE
LA English
DT Article
ID T-CELL DEVELOPMENT; GENE-EXPRESSION; PRECURSOR CELLS; GASTRIC-CANCER;
GROWTH; METHYLATION; METASTASIS; INHIBITION; DISCOVERY
AB Background: Pancreatic adenocarcinoma (PAC) is one of the most intractable malignancies. In order to search for potential new therapeutic targets, we relied on computational methods aimed at identifying transcription factor binding sites (TFBSs) over-represented in the promoter regions of genes differentially expressed in PAC. Though many computational methods have been implemented to accomplish this, none has gained overall acceptance or produced proven novel targets in PAC. To this end we have developed DEMON, a novel method for motif detection.
Methodology: DEMON relies on a hidden Markov model to score the appearance of sequence motifs, taking into account all potential sites in a promoter of potentially varying binding affinities. We demonstrate DEMON's accuracy on simulated and real data sets. Applying DEMON to PAC-related data sets identifies the RUNX family as highly enriched in PAC-related genes. Using a novel experimental paradigm to distinguish between normal and PAC cells, we find that RUNX3 mRNA (but not RUNX1 or RUNX2 mRNAs) exhibits time-dependent increases in normal but not in PAC cells. These increases are accompanied by changes in mRNA levels of putative RUNX gene targets.
Conclusions: The integrated application of DEMON and a novel differentiation system led to the identification of a single family member, RUNX3, which together with four of its putative targets showed a robust response to a differentiation stimulus in healthy cells, whereas this regulatory mechanism was absent in PAC cells, emphasizing RUNX3 as a promising target for further studies.
C1 [Levkovitz, Liron; Ruppin, Eytan; Oron, Yoram] Tel Aviv Univ, Sackler Fac Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel.
[Levkovitz, Liron; Yosef, Nir; Ruppin, Eytan; Sharan, Roded] Tel Aviv Univ, Sch Comp Sci, IL-69978 Tel Aviv, Israel.
[Gershengorn, Marvin C.] NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD USA.
RP Levkovitz, L (reprint author), Tel Aviv Univ, Sackler Fac Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel.
EM roded@post.tau.ac.il; medfair@post.tau.ac.il
FU Era-Net pathogenomics; Israel Cancer Association
FX This work was supported by an Era-Net pathogenomics grant to ER and RS,
and Israel Cancer Association grant to ER, RS and YO. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 36
TC 2
Z9 2
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 DEC 22
PY 2010
VL 5
IS 12
AR e14423
DI 10.1371/journal.pone.0014423
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 698FG
UT WOS:000285578000018
PM 21203558
ER
PT J
AU Miller, TW
Isenberg, JS
Shih, HB
Wang, YC
Roberts, DD
AF Miller, Thomas W.
Isenberg, Jeff S.
Shih, Hubert B.
Wang, Yichen
Roberts, David D.
TI Amyloid-beta Inhibits No-cGMP Signaling in a CD36-and CD47-Dependent
Manner
SO PLOS ONE
LA English
DT Article
ID SOLUBLE GUANYLATE-CYCLASE; ISCHEMIC TISSUE SURVIVAL; LONG-TERM
POTENTIATION; NITRIC-OXIDE SYNTHASE; ALZHEIMERS-DISEASE;
PLATELET-AGGREGATION; CELL RESPONSES; SMOOTH-MUSCLE; MICROGLIAL
PHAGOCYTOSIS; PRECURSOR PROTEIN
AB Amyloid-beta interacts with two cell surface receptors, CD36 and CD47, through which the matricellular protein thrombospondin-1 inhibits soluble guanylate cyclase activation. Here we examine whether amyloid-beta shares this inhibitory activity. Amyloid-beta inhibited both drug and nitric oxide-mediated activation of soluble guanylate cyclase in several cell types. Known cGMP-dependent functional responses to nitric oxide in platelets and vascular smooth muscle cells were correspondingly inhibited by amyloid-beta. Functional interaction of amyloid-beta with the scavenger receptor CD36 was indicated by inhibition of free fatty acid uptake via this receptor. Both soluble oligomer and fibrillar forms of amyloid-beta were active. In contrast, amyloid-beta did not compete with the known ligand SIRP alpha for binding to CD47. However, both receptors were necessary for amyloid-beta to inhibit cGMP accumulation. These data suggest that amyloid-beta interaction with CD36 induces a CD47-dependent signal that inhibits soluble guanylate cyclase activation. Combined with the pleiotropic effects of inhibiting free fatty acid transport via CD36, these data provides a molecular mechanism through which amyloid-beta can contribute to the nitric oxide signaling deficiencies associated with Alzheimer's disease.
C1 [Miller, Thomas W.; Isenberg, Jeff S.; Shih, Hubert B.; Wang, Yichen; Roberts, David D.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Isenberg, Jeff S.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA.
[Shih, Hubert B.] NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA.
RP Miller, TW (reprint author), NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM droberts@helix.nih.gov
RI Roberts, David/A-9699-2008; Miller, Thomas/G-1215-2011
OI Roberts, David/0000-0002-2481-2981; Miller, Thomas/0000-0001-8645-2785
FU National Institutes of Health (NIH), National Cancer Institute, Center
for Cancer Research [CA128616]; Howard Hughes Medical Institute-NIH
FX This work was supported by the Intramural Research Program of the
National Institutes of Health (NIH), National Cancer Institute, Center
for Cancer Research (D. D. R.), NIH grant CA128616 (J.S.I.) and by the
Howard Hughes Medical Institute-NIH Research Scholars Program (H. B.
S.). The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 60
TC 15
Z9 15
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD DEC 22
PY 2010
VL 5
IS 12
AR e15686
DI 10.1371/journal.pone.0015686
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 698FG
UT WOS:000285578000045
PM 21203512
ER
PT J
AU Teferedegne, B
Murata, H
Quinones, M
Peden, K
Lewis, AM
AF Teferedegne, Belete
Murata, Haruhiko
Quinones, Mariam
Peden, Keith
Lewis, Andrew M., Jr.
TI Patterns of microRNA Expression in Non-Human Primate Cells Correlate
with Neoplastic Development In Vitro
SO PLOS ONE
LA English
DT Article
ID HUMAN BREAST-CANCER; HUMAN TUMOR-CELLS; DOWN-REGULATION; VERO CELLS;
MESENCHYMAL TRANSITION; EPITHELIAL-CELLS; NKG2D; METASTASIS;
TRANSFORMATION; PROGRESSION
AB MicroRNAs (miRNAs) are small noncoding RNAs that negatively regulate gene expression post-transcriptionally. They play a critical role in developmental and physiological processes and have been implicated in the pathogenesis of several diseases including cancer. To identify miRNA signatures associated with different stages of neoplastic development, we examined the expression profile of 776 primate miRNAs in VERO cells (a neoplastically transformed cell line being used for the manufacture of viral vaccines), progenitor primary African green monkey kidney (pAGMK) cells, and VERO cell derivatives: spontaneously immortalized, non-tumorigenic, low-passage VERO cells (10-87 LP); tumorigenic, high-passage VERO cells (10-87 HP); and a cell line (10-87 T) derived from a 10-87 HP cell tumor xenograft in athymic nude mice. When compared with pAGMK cells, the majority of miRNAs were expressed at lower levels in 10-87 LP, 10-87 HP, and 10-87 T cells. We identified 10 up-regulated miRNAs whose level of expression correlated with VERO cell evolution from a non-tumorigenic phenotype to a tumorigenic phenotype. The overexpression of miR-376a and the polycistronic cluster of miR-376a, miR-376b and miR-376c conferred phenotypic changes to the non-tumorigenic 10-87 LP cells that mimic the tumorigenic 10-87 HP cells. Thirty percent of miRNAs that were components of the identified miRNAs in our spontaneously transformed AGMK cell model are also dysregulated in a variety of human tumors. These results may prove to be relevant to the biology of neoplastic development. In addition, one or more of these miRNAs could be biomarkers for the expression of a tumorigenic phenotype.
C1 [Teferedegne, Belete; Murata, Haruhiko; Lewis, Andrew M., Jr.] US FDA, Lab DNA Viruses, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA.
[Peden, Keith] US FDA, Lab Retrovirus Res, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA.
[Quinones, Mariam] NIH, Bioinformat & Computat Biosci Branch, Bethesda, MD 20892 USA.
RP Teferedegne, B (reprint author), US FDA, Lab DNA Viruses, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA.
EM andrew.lewis@fda.hhs.gov
FU Division of Microbiology and Infectious Diseases (DMID); National
Institute of Allergy and Infectious Diseases (NIAID) through Biologics
Evaluation and Research (CBER); Food and Drug Administration (FDA)
FX This work is partially supported by a contract from the Division of
Microbiology and Infectious Diseases (DMID), National Institute of
Allergy and Infectious Diseases (NIAID) through an interagency agreement
with Center for Biologics Evaluation and Research (CBER), Food and Drug
Administration (FDA). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 78
TC 13
Z9 13
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 DEC 22
PY 2010
VL 5
IS 12
AR e14416
DI 10.1371/journal.pone.0014416
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 698FG
UT WOS:000285578000017
PM 21203544
ER
PT J
AU Stoye, JP
Silverman, RH
Boucher, CA
Le Grice, SFJ
AF Stoye, Jonathan P.
Silverman, Robert H.
Boucher, Charles A.
Le Grice, Stuart F. J.
TI The xenotropic murine leukemia virus-related retrovirus debate continues
at first international workshop
SO RETROVIROLOGY
LA English
DT Review
ID CHRONIC-FATIGUE-SYNDROME; PROSTATE-CANCER; XMRV INFECTION; BLOOD;
SEQUENCES; FAILURE; CELLS; GENE
AB The 1(st) International Workshop on Xenotropic Murine Leukemia Virus-Related Retrovirus (XMRV), co-sponsored by the National Institutes of Health, The Department of Health and Human Services and Abbott Diagnostics, was convened on September 7/8, 2010 on the NIH campus, Bethesda, MD. Attracting an international audience of over 200 participants, the 2-day event combined a series of plenary talks with updates on different aspects of XMRV research, addressing basic gammaretrovirus biology, host response, association of XMRV with chronic fatigue syndrome and prostate cancer, assay development and epidemiology. The current status of XMRV research, concerns among the scientific community and suggestions for future actions are summarized in this meeting report.
C1 [Le Grice, Stuart F. J.] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA.
[Silverman, Robert H.] Cleveland Clin, Lerner Res Inst, Dept Canc Biol, Cleveland, OH 44195 USA.
[Stoye, Jonathan P.] Natl Inst Med Res, MRC, London NW7 1AA, England.
[Boucher, Charles A.] Univ Med Ctr Rotterdam, Dept Virol, Erasmus MC, Rotterdam, Netherlands.
RP Le Grice, SFJ (reprint author), NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA.
EM legrices@mail.nih.gov
FU Medical Research Council [MC_U117512710]
NR 31
TC 9
Z9 9
U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-4690
J9 RETROVIROLOGY
JI Retrovirology
PD DEC 22
PY 2010
VL 7
AR 113
DI 10.1186/1742-4690-7-113
PG 10
WC Virology
SC Virology
GA 708WN
UT WOS:000286395100001
PM 21176195
ER
PT J
AU Evans, G
Austin, F
AF Evans, Greg
Austin, Finley
TI Collaborations Among Academia, Government, and Industry in the
Diagnostics Space: Barriers and Some Ideas for Solutions
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Editorial Material
AB The development and commercialization of diagnostic assays is distinct from that of therapeutic drugs in many important respects; for example, there are more variable regulatory requirements and reduced outside investments for diagnostics. The diagnostics industry has a pro-collaborative stance, because there is considerable mutual benefit in working in partnership with university or government researchers. However, there are substantial barriers to industry-academic collaborations. A Clinical and Translational Science Awards Industry Forum titled "Promoting Efficient and Effective Collaborations Among Academia, Government, and Industry" was held in February 2010, and a session at this forum was organized to list some of the most important barriers to diagnostics development and to discuss some possible solutions.
C1 [Evans, Greg] NCI, NIH, US Dept Hlth & Human Serv, Small Business Innovat Res Dev Ctr, Bethesda, MD 20892 USA.
[Austin, Finley] Hoffman La Roche, Pharma Res & Early Dev, Translat Res Sci, Nutley, NJ 07110 USA.
RP Evans, G (reprint author), NCI, NIH, US Dept Hlth & Human Serv, Small Business Innovat Res Dev Ctr, Bethesda, MD 20892 USA.
EM evansgl@mail.nih.gov
FX This project was funded in whole or in part with Federal funds from the
National Center for Research Resources, NIH, through the CTSA program,
which is part of the Roadmap Initiative, Re-engineering the Clinical
Research Enterprise. The manuscript was approved by the CTSA Consortium
Publications Committee.
NR 0
TC 2
Z9 2
U1 2
U2 5
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD DEC 22
PY 2010
VL 2
IS 63
AR 63mr3
DI 10.1126/scitranslmed.3001633
PG 3
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 735UK
UT WOS:000288444900006
PM 21178133
ER
PT J
AU Portilla, LM
Evans, G
Eng, B
Fadem, TJ
AF Portilla, Lili M.
Evans, Greg
Eng, Benjamin
Fadem, Terry J.
TI Advancing Translational Research Collaborations
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
AB In February 2010, the U. S. National Institutes of Health (NIH) sponsored a national Clinical and Translational Science Awards forum titled "Promoting Efficient and Effective Collaborations among Academia, Government and Industry." This forum brought together a broad set of stakeholders who were charged with developing a path for promoting such partnerships. Here, we describe key issues discussed at the forum and plans for moving forward with this ambitious agenda.
C1 [Portilla, Lili M.] NIH, Natl Ctr Res Resources, Bethesda, MD 20892 USA.
[Evans, Greg] NCI, Small Business Innovat Res Dev Ctr, NIH, Bethesda, MD 20892 USA.
[Eng, Benjamin] Pfizer Inc, Med Acad, New York, NY 10017 USA.
[Fadem, Terry J.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
RP Portilla, LM (reprint author), NIH, Natl Ctr Res Resources, Bethesda, MD 20892 USA.
EM portilll@mail.nih.gov
FU NCRR; NIH, through the CTSA
FX This project has been funded in whole or in part with U.S. federal funds
from NCRR as well as NIH, through the CTSA, which is part of the Roadmap
Initiative, Re-Engineering the Clinical Research Enterprise. The
manuscript was approved by the CTSA Consortium Publications Committee.
NR 13
TC 4
Z9 4
U1 0
U2 6
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD DEC 22
PY 2010
VL 2
IS 63
AR 63cm30
DI 10.1126/scitranslmed.3001636
PG 4
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 735UK
UT WOS:000288444900002
PM 21178130
ER
PT J
AU Mozaffarian, D
Cao, HM
King, IB
Lemaitre, RN
Song, XL
Siscovick, DS
Hotamisligil, GS
AF Mozaffarian, Dariush
Cao, Haiming
King, Irena B.
Lemaitre, Rozenn N.
Song, Xiaoling
Siscovick, David S.
Hotamisligil, Goekhan S.
TI Trans-Palmitoleic Acid, Metabolic Risk Factors, and New-Onset Diabetes
in U.S. Adults A Cohort Study
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID CONJUGATED LINOLEIC-ACID; DE-NOVO LIPOGENESIS; NONFATAL
MYOCARDIAL-INFARCTION; INSULIN-RESISTANCE SYNDROME; SERUM-CHOLESTEROL
ESTERS; ISCHEMIC-HEART-DISEASE; C-REACTIVE PROTEIN; DAIRY FAT INTAKE;
ADIPOSE-TISSUE; HIGH-CARBOHYDRATE
AB Background: Palmitoleic acid (cis-16:1n-7), which is produced by endogenous fat synthesis, has been linked to both beneficial and deleterious metabolic effects, potentially confounded by diverse determinants and tissue sources of endogenous production. Trans-palmitoleate (trans-16:1n-7) represents a distinctly exogenous source of 16:1n-7, unconfounded by endogenous synthesis or its determinants, that may be uniquely informative.
Objective: To investigate whether circulating trans-palmitoleate is independently related to lower metabolic risk and incident type 2 diabetes.
Design: Prospective cohort study from 1992 to 2006.
Setting: Four U.S. communities.
Patients: 3736 adults in the Cardiovascular Health Study. Measurements: Anthropometric characteristics and levels of plasma phospholipid fatty acids, blood lipids, inflammatory markers, and glucose-insulin measured at baseline in 1992 and dietary habits measured 3 years earlier. Multivariate-adjusted models were used to investigate how demographic, clinical, and lifestyle factors independently related to plasma phospholipid trans-palmitoleate; how trans-palmitoleate related to major metabolic risk factors; and how trans-palmitoleate related to new-onset diabetes (304 incident cases). Findings were validated for metabolic risk factors in an independent cohort of 327 women.
Results: In multivariate analyses, whole-fat dairy consumption was most strongly associated with higher trans-palmitoleate levels. Higher trans-palmitoleate levels were associated with slightly lower adiposity and, independently, with higher high-density lipoprotein cholesterol levels (1.9% across quintiles; P = 0.040), lower triglyceride levels (-19.0%; P < 0.001), a lower total cholesterol-HDL cholesterol ratio (-4.7%; P < 0.001), lower C-reactive protein levels (-13.8%; P = 0.05), and lower insulin resistance (-16.7%, P < 0.001). Trans-palmitoleate was also associated with a substantially lower incidence of diabetes, with multivariate hazard ratios of 0.41 (95% CI, 0.27 to 0.64) and 0.38 (CI, 0.24 to 0.62) in quintiles 4 and 5 versus quintile 1 (P for trend < 0.001). Findings were independent of estimated dairy consumption or other fatty acid dairy biomarkers. Protective associations with metabolic risk factors were confirmed in the validation cohort.
Limitation: Results could be affected by measurement error or residual confounding.
Conclusion: Circulating trans-palmitoleate is associated with lower insulin resistance, presence of atherogenic dyslipidemia, and incident diabetes. Our findings may explain previously observed metabolic benefits of dairy consumption and support the need for detailed further experimental and clinical investigation.
C1 [Mozaffarian, Dariush] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA.
NIH, Bethesda, MD 20892 USA.
Univ New Mexico, Albuquerque, NM 87131 USA.
Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
Univ Washington, Seattle, WA 98195 USA.
RP Mozaffarian, D (reprint author), Harvard Univ, Sch Publ Hlth, 665 Huntington Ave,Bldg 2-319, Boston, MA 02115 USA.
EM dmozaffa@hsph.harvard.edu
RI Cao, Haiming/P-4634-2016
FU National Heart, Lung, and Blood Institute; National Institute of
Diabetes and Digestive and Kidney Diseases of the National Institutes of
Health [R01-HL085710, DK064360, DK71507-04, N01-HC-35129, N01-HC-45133,
N01-HC-75150, N01-HC-85079, -85086, N01-HC-15103, N01-HC-55222,
U01-HL080295]; Searle Scholar Award
FX National Heart, Lung, and Blood Institute and National Institute of
Diabetes and Digestive and Kidney Diseases of the National Institutes of
Health.; By the National Heart, Lung, and Blood Institute and National
Institute of Diabetes and Digestive and Kidney Diseases of the National
Institutes of Health (grants R01-HL085710, DK064360, and DK71507-04 and
grants N01-HC-35129, N01-HC-45133, N01-HC-75150, N01-HC-85079 through
-85086, N01-HC-15103, N01-HC-55222, and U01-HL080295 for the CHS), with
additional contributions from the National Institutes of Health Office
of Dietary Supplements and National Institute of Neurological Disorders
and Stroke. A subset of additional fatty acid measurements was supported
by a Searle Scholar Award.
NR 69
TC 128
Z9 131
U1 3
U2 18
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD DEC 21
PY 2010
VL 153
IS 12
BP 790
EP +
DI 10.7326/0003-4819-153-12-201012210-00005
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 696PL
UT WOS:000285453700002
PM 21173413
ER
PT J
AU Lichtenberg, J
Kurz, K
Liang, XY
Al-Ouran, R
Neiman, L
Nau, LJ
Welch, JD
Jacox, E
Bitterman, T
Ecker, K
Elnitski, L
Drews, F
Lee, SS
Welch, LR
AF Lichtenberg, Jens
Kurz, Kyle
Liang, Xiaoyu
Al-Ouran, Rami
Neiman, Lev
Nau, Lee J.
Welch, Joshua D.
Jacox, Edwin
Bitterman, Thomas
Ecker, Klaus
Elnitski, Laura
Drews, Frank
Lee, Stephen Sauchi
Welch, Lonnie R.
TI WordSeeker: concurrent bioinformatics software for discovering
genome-wide patterns and word-based genomic signatures
SO BMC BIOINFORMATICS
LA English
DT Article; Proceedings Paper
CT 11th Annual Bioinformatics Open Source Conference (BOSC)
CY JUL 09-10, 2010
CL Boston, MA
ID FACTOR-BINDING SITES; SEQUENCES; MOTIFS; GENES
AB Background: An important focus of genomic science is the discovery and characterization of all functional elements within genomes. In silico methods are used in genome studies to discover putative regulatory genomic elements (called words or motifs). Although a number of methods have been developed for motif discovery, most of them lack the scalability needed to analyze large genomic data sets.
Methods: This manuscript presents WordSeeker, an enumerative motif discovery toolkit that utilizes multi-core and distributed computational platforms to enable scalable analysis of genomic data. A controller task coordinates activities of worker nodes, each of which (1) enumerates a subset of the DNA word space and (2) scores words with a distributed Markov chain model.
Results: A comprehensive suite of performance tests was conducted to demonstrate the performance, speedup and efficiency of WordSeeker. The scalability of the toolkit enabled the analysis of the entire genome of Arabidopsis thaliana; the results of the analysis were integrated into The Arabidopsis Gene Regulatory Information Server (AGRIS). A public version of WordSeeker was deployed on the Glenn cluster at the Ohio Supercomputer Center.
Conclusion: WordSeeker effectively utilizes concurrent computing platforms to enable the identification of putative functional elements in genomic data sets. This capability facilitates the analysis of the large quantity of sequenced genomic data.
C1 [Lichtenberg, Jens; Kurz, Kyle; Liang, Xiaoyu; Al-Ouran, Rami; Neiman, Lev; Nau, Lee J.; Welch, Joshua D.; Ecker, Klaus; Drews, Frank; Welch, Lonnie R.] Ohio Univ, Sch EECS, Bioinformat Lab, Athens, OH 45701 USA.
[Jacox, Edwin] Dev Biol Inst Marseille, F-13009 Marseille, France.
[Bitterman, Thomas] Ohio Supercomp Ctr, Cyberinfrastruct Grp, Columbus, OH 43212 USA.
[Elnitski, Laura] NHGRI, Genom Funct Anal Sect, NIH, Bethesda, MD 20892 USA.
[Lee, Stephen Sauchi] Univ Idaho, Dept Stat, Moscow, ID 83844 USA.
[Welch, Lonnie R.] Ohio Univ, Biomed Engn Program, Athens, OH 45701 USA.
[Welch, Lonnie R.] Ohio Univ, Mol & Cellular Biol Program, Athens, OH 45701 USA.
RP Lichtenberg, J (reprint author), Ohio Univ, Sch EECS, Bioinformat Lab, Athens, OH 45701 USA.
EM lichtenj@ohio.edu
FU Intramural NIH HHS
NR 35
TC 2
Z9 2
U1 1
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD DEC 21
PY 2010
VL 11
SU 12
AR S6
DI 10.1186/1471-2105-11-S12-S6
PG 8
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA 759DA
UT WOS:000290219600006
PM 21210985
ER
PT J
AU Inoue, M
Yasuda, K
Uemura, H
Yasaka, N
Inoue, H
Sei, Y
Horikoshi, N
Fukuma, T
AF Inoue, Masahiro
Yasuda, Kouichi
Uemura, Haruki
Yasaka, Natsumi
Inoue, Hiroshi
Sei, Yoshitatsu
Horikoshi, Nobuo
Fukuma, Toshihide
TI Phosphorylation-Dependent Protein Interaction with Trypanosoma brucei
14-3-3 Proteins that Display Atypical Target Recognition
SO PLOS ONE
LA English
DT Article
ID 14-3-3-PROTEINS; BINDING; ISOFORMS; CYTOKINESIS; SPECIFICITY; GENOME;
KINASE; ZETA
AB Background: The 14-3-3 proteins are structurally conserved throughout eukaryotes and participate in protein kinase signaling. All 14-3-3 proteins are known to bind to evolutionally conserved phosphoserine-containing motifs (modes 1 and/or 2) with high affinity. In Trypanosoma brucei, 14-3-3I and II play pivotal roles in motility, cytokinesis and the cell cycle. However, none of the T. brucei 14-3-3 binding proteins have previously been documented.
Methodology/Principal Findings: Initially we showed that T. brucei 14-3-3 proteins exhibit far lower affinity to those peptides containing RSxpSxP (mode 1) and RxY/FxpSxP (mode 2) (where x is any amino acid residue and pS is phosphoserine) than human 14-3-3 proteins, demonstrating the atypical target recognition by T. brucei 14-3-3 proteins. We found that the putative T. brucei protein phosphatase 2C (PP2c) binds to T. brucei 14-3-3 proteins utilizing its mode 3 motif (-pS/pTx(1-2)-COOH, where x is not Pro). We constructed eight chimeric PP2c proteins replacing its authentic mode 3 motif with potential mode 3 sequences found in Trypanosoma brucei genome database, and tested their binding. As a result, T. brucei 14-3-3 proteins interacted with three out of eight chimeric proteins including two with high affinity. Importantly, T. brucei 14-3-3 proteins co-immunoprecipitated with an uncharacterized full-length protein containing identified high-affinity mode 3 motif, suggesting that both proteins form a complex in vivo. In addition, a synthetic peptide derived from this mode 3 motif binds to T. brucei 14-3-3 proteins with high affinity.
Conclusion/Significance: Because of the atypical target recognition of T. brucei 14-3-3 proteins, no 14-3-3-binding proteins have been successfully identified in T. brucei until now whereas over 200 human 14-3-3-binding proteins have been identified. This report describes the first discovery of the T. brucei 14-3-3-binding proteins and their binding motifs. The high-affinity phosphopeptide will be a powerful tool to identify novel T. brucei 14-3-3-binding proteins.
C1 [Inoue, Masahiro; Yasuda, Kouichi; Yasaka, Natsumi; Inoue, Hiroshi; Fukuma, Toshihide] Kurume Univ, Sch Med, Dept Infect Med, Div Eukaryot Microbiol, Kurume, Fukuoka 830, Japan.
[Uemura, Haruki] Nagasaki Univ, Inst Trop Med, Dept Protozool, Nagasaki 852, Japan.
[Sei, Yoshitatsu] NIDDK, Gastroenterol Sect, Digest Dis Branch, Bethesda, MD USA.
[Horikoshi, Nobuo] SW Texas State Univ, Div Mol Radiat Biol, Dept Radiat Oncol, Sch Med, Dallas, TX USA.
RP Inoue, M (reprint author), Kurume Univ, Sch Med, Dept Infect Med, Div Eukaryot Microbiol, Kurume, Fukuoka 830, Japan.
EM inouedna@med.kurume-u.ac.jp
FU Ministry of Education, Science, Sports and Culture, Grant-in-Aid for
Scientific Research [2009, 20590434]; Institute of Tropical Medicine,
Nagasaki University [2008-20-D-2, 2009-21-E-8]; Ishibashi Foundation for
the Promotion of Science
FX This research was supported by the Ministry of Education, Science,
Sports and Culture, Grant-in-Aid for Scientific Research (C), 2009,
20590434, by the Cooperative Research Grant(s) (2008-20-D-2,
2009-21-E-8, 9) of the Institute of Tropical Medicine, Nagasaki
University, and by a grant from the Ishibashi Foundation for the
Promotion of Science. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 23
TC 5
Z9 5
U1 0
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 DEC 21
PY 2010
VL 5
IS 12
AR e15566
DI 10.1371/journal.pone.0015566
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 698EY
UT WOS:000285576900032
PM 21203569
ER
PT J
AU Khodyreva, SN
Prasad, R
Ilina, ES
Sukhanova, MV
Kutuzov, MM
Liu, Y
Hou, EW
Wilson, SH
Lavrik, OI
AF Khodyreva, S. N.
Prasad, R.
Ilina, E. S.
Sukhanova, M. V.
Kutuzov, M. M.
Liu, Y.
Hou, E. W.
Wilson, S. H.
Lavrik, O. I.
TI Apurinic/apyrimidinic (AP) site recognition by the 5 '-dRP/AP lyase in
poly(ADP-ribose) polymerase-1 (PARP-1)
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE Schiff base; apurinic/apyrimidinic site-binding protein
ID BASE-EXCISION-REPAIR; DNA-REPAIR; ABASIC SITES; MAMMALIAN-CELLS; BETA;
ENDONUCLEASE; DAMAGE; PROTEINS; CLEAVAGE; ENZYMES
AB The capacity of human poly(ADP-ribose) polymerase-1 (PARP-1) to interact with intact apurinic/apyrimidinic (AP) sites in DNA has been demonstrated. In cell extracts, sodium borohydride reduction of the PARP-1/AP site DNA complex resulted in covalent cross-linking of PARP-1 to DNA; the identity of cross-linked PARP-1 was confirmed by mass spectrometry. Using purified human PARP-1, the specificity of PARP-1 binding to AP site-containing DNA was confirmed in competition binding experiments. PARP-1 was only weakly activated to conduct poly(ADP-ribose) synthesis upon binding to AP site-containing DNA, but was strongly activated for poly (ADP-ribose) synthesis upon strand incision by AP endonuclease 1 (APE1). By virtue of its binding to AP sites, PARP-1 could be poised for its role in base excision repair, pending DNA strand incision by APE1 or the 5'-dRP/AP lyase activity in PARP-1.
C1 [Khodyreva, S. N.; Ilina, E. S.; Sukhanova, M. V.; Kutuzov, M. M.; Lavrik, O. I.] Russian Acad Sci, Inst Chem Biol & Fundamental Med, Siberian Branch, Novosibirsk, Russia.
[Prasad, R.; Liu, Y.; Hou, E. W.; Wilson, S. H.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
RP Lavrik, OI (reprint author), Russian Acad Sci, Inst Chem Biol & Fundamental Med, Siberian Branch, Novosibirsk, Russia.
EM lavrik@niboch.nsc.ru
RI Kutuzov, Mikhail/G-4239-2013; Ilina , Ekaterina/G-4224-2013; Khodyreva,
Svetlana/G-4659-2013; Lavrik, Olga /G-4641-2013
FU Russian Foundation for Basic Research [10-04-01083, 09-04-93106,
09-04-91320 (HRJRG-102)]; RAS; National Institutes of Health, National
Institute of Environmental Health Sciences [Z01-ES050158, Z01-ES050159];
[02.740.11.0079]
FX We thank Dr. Yu. Gerasimova (Institute of Chemical Biology and
Fundamental Medicine, SB RAS) for recording the MALDI-TOF-MS spectra.
The authors also thank Bonnie Mesmer for assistance in manuscript
preparation. This work was supported in part by the Russian Foundation
for Basic Research [Projects 10-04-01083, 09-04-93106, and 09-04-91320
(HRJRG-102)], the Program of RAS "Molecular and Cellular Biology," and
State Contract 02.740.11.0079. This work also was supported in part by
Research Projects Z01-ES050158 and Z01-ES050159 in the Intramural
Research Program of the National Institutes of Health, National
Institute of Environmental Health Sciences.
NR 38
TC 48
Z9 53
U1 0
U2 7
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD DEC 21
PY 2010
VL 107
IS 51
BP 22090
EP 22095
DI 10.1073/pnas.1009182107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 697OB
UT WOS:000285521800031
PM 21127267
ER
PT J
AU Song, KM
Bolton, DL
Wilson, RL
Camp, JV
Bao, SR
Mattapallil, JJ
Herzenberg, LA
Herzenberg, LA
Andrews, CA
Sadoff, JC
Goudsmit, J
Pau, MG
Seder, RA
Kozlowski, PA
Nabel, GJ
Roederer, M
Rao, SS
AF Song, Kaimei
Bolton, Diane L.
Wilson, Robert L.
Camp, Jeremy V.
Bao, Saran
Mattapallil, Joseph J.
Herzenberg, Leonore A.
Herzenberg, Leonard A.
Andrews, Charla A.
Sadoff, Jerald C.
Goudsmit, Jaap
Pau, Maria Grazia
Seder, Robert A.
Kozlowski, Pamela A.
Nabel, Gary J.
Roederer, Mario
Rao, Srinivas S.
TI Genetic immunization in the lung induces potent local and systemic
immune responses
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE mucosal responses; tuberculosis; platform immunization
ID NEUTRALIZING ANTIBODIES; VACCINE VECTORS; RHESUS-MONKEYS; VIRUS;
PROTECTION; INFLUENZA; IMMUNOGENICITY; INTERFERON; POULTRY; FERRETS
AB Successful vaccination against respiratory infections requires elicitation of high levels of potent and durable humoral and cellular responses in the lower airways. To accomplish this goal, we used a fine aerosol that targets the entire lung surface through normal respiration to deliver replication-incompetent recombinant adenoviral vectors expressing gene products from several infectious pathogens. We show that this regimen induced remarkably high and stable lung T-cell responses in nonhuman primates and that it also generated systemic and respiratory tract humoral responses of both IgA and IgG isotypes. Moreover, strong immunogenicity was achieved even in animals with preexisting antiadenoviral immunity, overcoming a critical hurdle to the use of these vectors in humans, who commonly are immune to adenoviruses. The immunogenicity profile elicited with this regimen, which is distinct from either intramuscular or intranasal delivery, has highly desirable properties for protection against respiratory pathogens. We show that it can be used repeatedly to generate mucosal humoral, CD4, and CD8 T-cell responses and as such may be applicable to other mucosally transmitted pathogens such as HIV. Indeed, in a lethal challenge model, we show that aerosolized recombinant adenoviral immunization completely protects ferrets against H5N1 highly pathogenic avian influenza virus. Thus, genetic immunization in the lung offers a powerful platform approach to generating protective immune responses against respiratory pathogens.
C1 Stanford Univ, Dept Genet, Stanford, CA 94305 USA.
[Song, Kaimei; Bolton, Diane L.; Bao, Saran; Andrews, Charla A.; Seder, Robert A.; Nabel, Gary J.; Roederer, Mario; Rao, Srinivas S.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Wilson, Robert L.; Camp, Jeremy V.; Kozlowski, Pamela A.] Louisiana State Univ, Hlth Sci Ctr, Gene Therapy Program, New Orleans, LA 70803 USA.
[Wilson, Robert L.; Camp, Jeremy V.; Kozlowski, Pamela A.] Louisiana State Univ, Hlth Sci Ctr, Dept Microbiol Immunol & Parasitol, New Orleans, LA 70803 USA.
[Mattapallil, Joseph J.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
[Sadoff, Jerald C.] AERAS Global TB Fdn, Rockville, MD 20850 USA.
[Goudsmit, Jaap; Pau, Maria Grazia] Crucell Holland BV, Leiden, Netherlands.
RP Herzenberg, LA (reprint author), Stanford Univ, Dept Genet, Stanford, CA 94305 USA.
EM lenherz@darwin.stanford.edu; lenherz@darwin.stanford.edu;
roederer@nih.gov
FU National Institute of Allergy and Infectious Diseases [AI058896,
AI077395]; National Institute of Allergy and Infectious Diseases,
National Institutes of Health
FX We thank Judy Stein for assistance with technology transfer, Robert
Phelps of PARI Pharma GmbH (Munich, Germany) for providing valuable
information and assistance with customization of the device, John-Paul
Todd and Alida Ault for assistance with animal protocols and procedures,
and the BioQual staff for animal support. This work was supported by
National Institute of Allergy and Infectious Diseases Grant AI058896 (to
P.A.K.), AI077395 (to L.A.H.), and by the Intramural Research Program of
the National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 24
TC 37
Z9 38
U1 0
U2 6
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD DEC 21
PY 2010
VL 107
IS 51
BP 22213
EP 22218
DI 10.1073/pnas.1015536108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 697OB
UT WOS:000285521800052
PM 21135247
ER
PT J
AU Lu, W
Isozaki, K
Roche, KW
Nicoll, RA
AF Lu, Wei
Isozaki, Kaname
Roche, Katherine W.
Nicoll, Roger A.
TI Synaptic targeting of AMPA receptors is regulated by a CaMKII site in
the first intracellular loop of GluA1
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE GluA2; GluR1; postsynaptic density; hippocampus; pyramidal neurons
ID LONG-TERM POTENTIATION; CA1 PYRAMIDAL CELLS; GLUTAMATE-RECEPTOR;
PHOSPHORYLATION SITES; HIPPOCAMPAL-NEURONS; LATERAL MOVEMENTS; GLUR1
SUBUNIT; PLASTICITY; TRAFFICKING; SYNAPSES
AB The accumulation of AMPA receptors (AMPARs) at synapses is essential for excitatory synaptic transmission. However, the mechanisms underlying synaptic targeting of AMPARs remain elusive. We have now used a molecular replacement approach on an AMPAR-null background to investigate the targeting mechanisms necessary for regulating AMPAR trafficking in the hippocampus. Although there is an extensive literature on the role of the GluA1 C-tail in AMPAR trafficking, there is no effect of overexpressing the C-tail on basal transmission. Instead, we found that the first intracellular loop domain (Loop1) of GluA1, a previously overlooked region within AMPARs, is critical for receptor targeting to synapses, but not for delivery of receptors to the plasma membrane. We also identified a CaMKII phosphorylation site (S567) in the GluA1 Loop1, which is phosphorylated in vitro and in vivo. Furthermore, we show that S567 is a key residue that regulates Loop1-mediated AMPAR trafficking. Thus, our study reveals a unique mechanism for targeting AMPARs to synapses to mediate synaptic transmission.
C1 [Lu, Wei; Nicoll, Roger A.] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA.
[Isozaki, Kaname; Roche, Katherine W.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA.
[Lu, Wei; Nicoll, Roger A.] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA.
RP Nicoll, RA (reprint author), Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA.
EM rochek@ninds.nih.gov; nicoll@cmp.ucsf.edu
RI Lu, Wei/E-8110-2011;
OI Roche, Katherine/0000-0001-7282-6539
FU American Heart Association; Japan Society for the Promotion of Scienc at
the National Institutes of Health; NINDS; National Institute of Mental
Health
FX We thank K. Bjorgan and M. Cerpas for technical assistance, and all
members from the R.A.N. laboratory and K.W.R. laboratory for helpful
discussions. We are also grateful for the generosity of Profs. Peter
Seeburg and Rolf Sprengel at The Max Planck Institute for Medical
Research (Heidelberg, Germany) for sharing individual gene targeted
conditional mice for GluA1, GluA2, or GluA3, from which we were able to
make the triple floxed Gria1-3fl/fl mice. We also thank the
National Institute of Neurological Disorders and Stroke (NINDS) Light
Imaging Facility, particularly C. Smith, and the NINDS sequencing
facility for DNA sequencing. W.L. is funded by a postdoctoral fellowship
from the American Heart Association; K.I. is funded by the Japan Society
for the Promotion of Science Research Fellowship for Japanese Biomedical
and Behavioral Researchers at the National Institutes of Health; K.W.R.
is funded by the NINDS Intramural Research Program; and R.A.N. is funded
by grants from the National Institute of Mental Health.
NR 41
TC 33
Z9 34
U1 0
U2 9
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD DEC 21
PY 2010
VL 107
IS 51
BP 22266
EP 22271
DI 10.1073/pnas.1016289107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 697OB
UT WOS:000285521800061
PM 21135237
ER
PT J
AU Thanos, PK
Tucci, A
Stamos, J
Robison, L
Wang, GJ
Anderson, BJ
Volkow, ND
AF Thanos, Panayotis K.
Tucci, Andrew
Stamos, Joshua
Robison, Lisa
Wang, Gene-Jack
Anderson, Brenda J.
Volkow, Nora D.
TI Chronic forced exercise during adolescence decreases cocaine conditioned
place preference in Lewis rats
SO BEHAVIOURAL BRAIN RESEARCH
LA English
DT Article
DE Dopamine; Exercise; Cocaine; Conditioned place preference
ID DOPAMINE D2 RECEPTOR; DIET-INDUCED OBESITY; SEX-DIFFERENCES; FEMALE
RATS; LOCOMOTOR-ACTIVITY; AEROBIC EXERCISE; BIOLOGICAL BASIS; BRAIN
DOPAMINE; FIRING RATE; WHEEL
AB Chronic physical activity (exercise) may be beneficial in the prevention of substance use disorders; however, the extent to which physical activity can interfere with the reinforcing effects of drugs during the adolescent period, which is one of great vulnerability for drug experimentation, has not been fully evaluated. Here, we assess the effects of chronic forced exercise during adolescence on preference for cocaine using the conditioned place preference (CPP) paradigm in male and female Lewis rats. The group of rats exposed to exercise ran on a treadmill for 6 weeks on a progressive time-increased schedule for up to 1 h of exercise per day, while the groups of sedentary rats remained in their home cage. Following the 6 weeks of exercise exposure, rats were tested for cocaine CPP. Results showed that chronic exercise significantly attenuated cocaine CPP in both males and females compared to a sedentary environment. Furthermore, male exercise rats failed to show significant cocaine CPP. In contrast, female exercise rats still showed cocaine CPP but it was significantly reduced compared to the female sedentary rats. Females also exhibited greater cocaine CPP than males overall. These findings suggest that strategies to promote physical activity during adolescence may be protective against cocaine abuse in both males and females, and these findings merit further investigation. We also corroborate a gender-specific sensitivity to the reinforcing effects of cocaine, highlighting the need to consider gender-tailored exercise interventions for drug abuse prevention. (C) 2010 Published by Elsevier B.V.
C1 [Thanos, Panayotis K.; Tucci, Andrew; Stamos, Joshua; Wang, Gene-Jack] Brookhaven Natl Lab, Dept Med, Behav Neuropharmacol & Neuroimaging Lab, Upton, NY 11973 USA.
[Thanos, Panayotis K.; Robison, Lisa; Volkow, Nora D.] NIAAA, Lab Neuroimaging, NIH, Bethesda, MD 20892 USA.
[Thanos, Panayotis K.; Anderson, Brenda J.] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA.
RP Thanos, PK (reprint author), Brookhaven Natl Lab, Dept Med, Behav Neuropharmacol & Neuroimaging Lab, Upton, NY 11973 USA.
EM thanos@bnl.gov
FU NIAAA [AA 11034, AA07574, AA07611]; SULI; IRTA
FX This work was supported by the NIAAA (AA 11034 & AA07574, AA07611). We
also thank the SULI and IRTA programs for partial support of LSR. We
also thank Joe Gatz for technical assistance with the equipment.
NR 60
TC 23
Z9 24
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-4328
J9 BEHAV BRAIN RES
JI Behav. Brain Res.
PD DEC 20
PY 2010
VL 215
IS 1
BP 77
EP 82
DI 10.1016/j.bbr.2010.06.033
PG 6
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 653GG
UT WOS:000282076500010
PM 20615434
ER
PT J
AU Barak, B
Williams, A
Bielopolski, N
Gottfried, I
Okun, E
Brown, MA
Matti, U
Rettig, J
Stuenkel, EL
Ashery, U
AF Barak, Boaz
Williams, Antionette
Bielopolski, Noa
Gottfried, Irit
Okun, Eitan
Brown, Meghan A.
Matti, Ulf
Rettig, Jens
Stuenkel, Edward L.
Ashery, Uri
TI Tomosyn expression pattern in the mouse hippocampus suggests both
presynaptic and postsynaptic functions
SO FRONTIERS IN NEUROANATOMY
LA English
DT Article
DE tomosyn isoforms; hippocampus; mossy fiber terminals; CA2 area; synaptic
protein
AB The protein tomosyn decreases synaptic transmission and release probability of vesicles, and is essential for modulating synaptic transmission in neurons. In this study, we provide a detailed description of the expression and localization patterns of tomosyn1 and tomosyn2 in the subareas of the mouse hippocampus. Using confocal and two-photon high-resolution microscopy we demonstrate that tomosyn colocalizes with several pre- and postsynaptic markers and is found mainly in glutamatergic synapses. Specifically, we show that tomosyn1 is differentially distributed in the mouse hippocampus and concentrated mainly in the hilus and mossy fibers. Surprisingly, we found that tomosyn2 is expressed in the subiculum, CA1 and CA2 pyramidal cell bodies, dendrites and spines, and colocalizes with PSD95, suggesting a postsynaptic role. These results suggest that in addition to the well-characterized presynaptic function of tomosyn in neurotransmitter release, tomosyn2 might have a postsynaptic function, and place tomosyn as a more general regulator of synaptic transmission and plasticity.
C1 [Barak, Boaz; Bielopolski, Noa; Gottfried, Irit; Ashery, Uri] Tel Aviv Univ, George S Wise Fac Life Sci, Dept Neurobiol, IL-69978 Tel Aviv, Israel.
[Williams, Antionette; Stuenkel, Edward L.] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA.
[Okun, Eitan; Brown, Meghan A.] NIA, Neurosci Lab, NIH, Baltimore, MD 21224 USA.
[Matti, Ulf; Rettig, Jens] Univ Saarland, Inst Physiol, Homburg, Saar, Germany.
RP Ashery, U (reprint author), Tel Aviv Univ, George S Wise Fac Life Sci, Dept Neurobiol, Sherman Bldg Room 719, IL-69978 Tel Aviv, Israel.
EM uria@post.tau.ac.il
RI Rettig, Jens/K-5103-2013; okun, eitan/K-1314-2016;
OI Rettig, Jens/0000-0001-6160-3954; okun, eitan/0000-0001-8474-1487;
Matti, Ulf/0000-0001-5548-1081
FU Israel Science Foundation [1211/07]; National Institutes of Health [RO1
NS053978]
FX We thank Dr. E. F. Indig, Dr. M. Shaharabany and Dr. E. Krause for their
technical help. Tomosyn1-knockout mice were kindly provided by Prof. Y.
Takai, Kobe University and Prof. J. Miyoshi, Osaka, Japan. This work was
supported by grants from the Israel Science Foundation (Grant no.
1211/07; Uri Ashery) and the National Institutes of Health (RO1
NS053978; Edward L. Stuenkel and Uri Ashery).
NR 44
TC 9
Z9 9
U1 0
U2 5
PU FRONTIERS RES FOUND
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1662-5129
J9 FRONT NEUROANAT
JI Front. Neuroanat.
PD DEC 20
PY 2010
VL 4
AR 149
DI 10.3389/fnana.2010.00149
PG 11
WC Anatomy & Morphology; Neurosciences
SC Anatomy & Morphology; Neurosciences & Neurology
GA V21HY
UT WOS:000208199900001
PM 21191478
ER
PT J
AU Ishii, M
Kikuta, J
Shimazu, Y
Meier-Schellersheim, M
Germain, RN
AF Ishii, Masaru
Kikuta, Junichi
Shimazu, Yutaka
Meier-Schellersheim, Martin
Germain, Ronald N.
TI Chemorepulsion by blood S1P regulates osteoclast precursor mobilization
and bone remodeling in vivo
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID SPHINGOSINE-1-PHOSPHATE RECEPTORS; SPHINGOSINE 1-PHOSPHATE;
CELL-MIGRATION; T-CELLS; CHEMOKINE; EXPRESSION; MARROW
AB Sphingosine-1-phosphate (S1P), a lipid mediator enriched in blood, controls the dynamic migration of osteoclast (OC) precursors (OPs) between the blood and bone, in part via the S1P receptor 1 (S1PR1) which directs positive chemotaxis toward S1P. We show that OPs also express S1PR2, an S1P receptor which mediates negative chemotaxis (or chemorepulsion). OP-positive chemotaxis is prominent in gradients with low maximal concentrations of S1P, whereas such behavior is minimal in fields with high maximal S1P concentrations. This reverse-directional behavior is caused by S1PR2-mediated chemorepulsion acting to override S1PR1 upgradient motion. S1PR2-deficient mice exhibit moderate osteopetrosis as a result of a decrease in osteoclastic bone resorption, suggesting that S1PR2 contributes to OP localization on the bones mediated by chemorepulsion away from the blood where S1P levels are high. Inhibition of S1PR2 function by the antagonist JTE013 changed the migratory behavior of monocytoid cells, including OPs, and relieved osteoporosis in a mouse model by limiting OP localization and reducing the number of mature OCs attached to the bone surface. Thus, reciprocal regulation of S1P-dependent chemotaxis controls bone remodeling by finely regulating OP localization. This regulatory axis may be promising as a therapeutic target in diseases affecting OC-dependent bone remodeling.
C1 [Ishii, Masaru; Kikuta, Junichi; Shimazu, Yutaka] Osaka Univ, Lab Biol Imaging, WPI Immunol Frontier Res Ctr, Suita, Osaka 5650871, Japan.
[Ishii, Masaru; Germain, Ronald N.] NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Meier-Schellersheim, Martin; Germain, Ronald N.] NIAID, Program Syst Immunol & Infect Dis Modeling, NIH, Bethesda, MD 20892 USA.
RP Ishii, M (reprint author), Osaka Univ, Lab Biol Imaging, WPI Immunol Frontier Res Ctr, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan.
EM mishii@ifrec.osaka-u.ac.jp; rgermain@niaid.nih.gov
RI Ishii, Masaru/D-2361-2009;
OI Shimazu, Yutaka/0000-0002-1604-7220
FU National Institute of Allergy and Infectious Diseases, NIH; United
States Department of Health and Human Services; International Human
Frontier Science Program [00387/2006-L, CDA-00059/2009]; Senri
Lifescience Foundation; Scientific Research on Innovative Areas
[22113007]; Ministry of Education, Science, Sports and Culture of Japan;
Ministry of Health, Labor and Welfare of Japan [H21-010]; Takeda Science
Foundation; Japan Research Foundation for Clinical Pharmacology; Senri
Lifescience Foundation; Mochida Memorial Foundation for Medical and
Pharmaceutical Research
FX This work was supported in part by the Intramural Research Program of
the National Institute of Allergy and Infectious Diseases, NIH, United
States Department of Health and Human Services (R.N. Germain), by grants
from the International Human Frontier Science Program (LT-00387/2006-L
and CDA-00059/2009; to M. Ishii), by a Grants-in-Aid for Encouragement
of Young Scientists (A; 22689030), for Scientific Research on Innovative
Areas (22113007; to M. Ishii), and a Funding Program for World-Leading
Innovative R&D on Science and Technology (FIRST Program) from the
Ministry of Education, Science, Sports and Culture of Japan, by
Grants-in-Aid for Research on Allergic Disease and Immunology (H21-010;
to M. Ishii) from the Ministry of Health, Labor and Welfare of Japan,
and by Grants from Takeda Science Foundation (to M. Ishii), from Japan
Research Foundation for Clinical Pharmacology (to M. Ishii), from Senri
Lifescience Foundation (to M. Ishii), and from Mochida Memorial
Foundation for Medical and Pharmaceutical Research (to M. Ishii).
NR 21
TC 87
Z9 92
U1 0
U2 7
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD DEC 20
PY 2010
VL 207
IS 13
BP 2793
EP 2798
DI 10.1084/jem.20101474
PG 6
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 697HD
UT WOS:000285503000003
PM 21135136
ER
PT J
AU Geldmacher, C
Ngwenyama, N
Schuetz, A
Petrovas, C
Reither, K
Heeregrave, EJ
Casazza, JP
Ambrozak, DR
Louder, M
Ampofo, W
Pollakis, G
Hill, B
Sanga, E
Saathoff, E
Maboko, L
Roederer, M
Paxton, WA
Hoelscher, M
Koup, RA
AF Geldmacher, Christof
Ngwenyama, Njabulo
Schuetz, Alexandra
Petrovas, Constantinos
Reither, Klaus
Heeregrave, Edwin J.
Casazza, Joseph P.
Ambrozak, David R.
Louder, Mark
Ampofo, William
Pollakis, Georgios
Hill, Brenna
Sanga, Erica
Saathoff, Elmar
Maboko, Leonard
Roederer, Mario
Paxton, William A.
Hoelscher, Michael
Koup, Richard A.
TI Preferential infection and depletion of Mycobacterium
tuberculosis-specific CD4 T cells after HIV-1 infection
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID AFRICAN GOLD MINERS; IN-VIVO; SIV REPLICATION; FLOW-CYTOMETRY; MBEYA
REGION; IFN-GAMMA; IMMUNODEFICIENCY; RESPONSES; DISEASE; MICE
AB HIV-1 infection results in the progressive loss of CD4 T cells. In this study, we address how different pathogen-specific CD4 T cells are affected by HIV infection and the cellular parameters involved. We found striking differences in the depletion rates between CD4 T cells to two common opportunistic pathogens, cytomegalovirus (CMV) and Mycobacterium tuberculosis (MTB). CMV-specific CD4 T cells persisted after HIV infection, whereas MTB-specific CD4 T cells were depleted rapidly. CMV-specific CD4 T cells expressed a mature phenotype and produced very little IL-2, but large amounts of MIP-1 beta. In contrast, MTB-specific CD4 T cells were less mature, and most produced IL-2 but not MIP-1 beta. Staphylococcal enterotoxin B-stimulated IL-2-producing cells were more susceptible to HIV infection in vitro than MIP-1 beta-producing cells. Moreover, IL-2 production was associated with expression of CD25, and neutralization of IL-2 completely abrogated productive HIV infection in vitro. HIV DNA was found to be most abundant in IL-2-producing cells, and least abundant in MIP-1 beta-producing MTB-specific CD4 T cells from HIV-infected subjects with active tuberculosis. These data support the hypothesis that differences in function affect the susceptibility of pathogen-specific CD4 T cells to HIV infection and depletion in vivo, providing a potential mechanism to explain the rapid loss of MTB-specific CD4 T cells after HIV infection.
C1 [Geldmacher, Christof; Ngwenyama, Njabulo; Petrovas, Constantinos; Casazza, Joseph P.; Ambrozak, David R.; Hill, Brenna; Koup, Richard A.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Roederer, Mario] NIAID, Immunotechnol Sect, NIH, Bethesda, MD 20892 USA.
[Louder, Mark] NIAID, Core Virol Sect BSL 3, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Schuetz, Alexandra; Reither, Klaus; Sanga, Erica; Maboko, Leonard] Referral Hosp, Natl Inst Med Res, Mbeya Med Res Programme, Mbeya, Tanzania.
[Heeregrave, Edwin J.; Pollakis, Georgios; Paxton, William A.] Univ Amsterdam, Dept Retrovirol, NL-1105 AZ Amsterdam, Netherlands.
[Geldmacher, Christof; Reither, Klaus; Saathoff, Elmar; Hoelscher, Michael] Klinikum Univ Munich, Dept Infect Dis & Trop Med, D-80802 Munich, Germany.
[Ampofo, William] Univ Ghana, Noguchi Mem Inst Med Res, Accra, Ghana.
RP Geldmacher, C (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM geldmacher@lrz.uni-muenchen.de
RI Hoelscher, Michael/D-3436-2012;
OI Pollakis, Georgios/0000-0002-9659-5461
FU European Commission [ICA_CT-1999-10007, ICA_CT-2002-10048, E.C. DGVIII -
AIDCO - SANTE/2006/129-931]; Netherlands Organisation for Scientific
Research WOTRO [01.53.2004.025]
FX This study has been supported by the European Commission through grants
ICA_CT-1999-10007, ICA_CT-2002-10048, and E.C. DGVIII - AIDCO -
SANTE/2006/129-931 and a Netherlands Organisation for Scientific
Research WOTRO Grant (01.53.2004.025).
NR 49
TC 101
Z9 103
U1 0
U2 3
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD DEC 20
PY 2010
VL 207
IS 13
BP 2869
EP 2881
DI 10.1084/jem.20100090
PG 13
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 697HD
UT WOS:000285503000010
PM 21115690
ER
PT J
AU Kemble, CK
Auxier, J
Lynch, SK
Bennett, EE
Morgan, NY
Wen, H
AF Kemble, Camille K.
Auxier, Julie
Lynch, Susanna K.
Bennett, Eric E.
Morgan, Nicole Y.
Wen, Han
TI Grazing angle Mach-Zehnder interferometer using reflective phase
gratings and a polychromatic, un-collimated light source
SO OPTICS EXPRESS
LA English
DT Article
ID RAY; TISSUES
AB Normal incidence Talbot-Lau interferometers in x-ray applications have the drawbacks of low fringe visibility with polychromatic sources when the wave propagation distance is increased to achieve higher phase sensitivity, and when fabrication limits the attainable grating density. In contrast, reflective gratings illuminated at grazing angles have dramatically higher effective densities than their physical values. However, new designs are needed for far field interferometers using grazing angle geometry with incoherent light sources. We show that, with the appropriate design and choice of reflective phase gratings, there exist pairs of interfering pathways of exactly equal lengths independent of the incoming beam's incidence angle and wavelength. With a visible light grazing angle Mach-Zehnder interferometer, we show the conditions for achieving near ideal fringe visibility and demonstrate both absolute and differential phase-contrast imaging. We also describe the design parameters of an x-ray interferometer and key factors for its implementation. (C) 2010 Optical Society of America
C1 [Kemble, Camille K.; Lynch, Susanna K.; Bennett, Eric E.; Wen, Han] NHLBI, Imaging Phys Sect, NIH, Bethesda, MD 20892 USA.
[Auxier, Julie] Natl Inst Biomed Imaging & Bioengn, Intramural Res Programs, NIH, Bethesda, MD 20892 USA.
RP Kemble, CK (reprint author), NHLBI, Imaging Phys Sect, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM wenh@nhlbi.nih.gov
RI Bennett, Eric/A-2551-2013; Wen, Han/G-3081-2010
OI Wen, Han/0000-0001-6844-2997
FU Intramural NIH HHS [ZIA HL004606-14]
NR 19
TC 7
Z9 7
U1 0
U2 8
PU OPTICAL SOC AMER
PI WASHINGTON
PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA
SN 1094-4087
J9 OPT EXPRESS
JI Opt. Express
PD DEC 20
PY 2010
VL 18
IS 26
BP 27481
EP 27492
DI 10.1364/OE.18.027481
PG 12
WC Optics
SC Optics
GA 698HF
UT WOS:000285584200114
PM 21197023
ER
PT J
AU Ma, LA
Jensen, JS
Mancuso, M
Hamasuna, R
Jia, QY
McGowin, CL
Martin, DH
AF Ma, Liang
Jensen, Jorgen S.
Mancuso, Miriam
Hamasuna, Ryoichi
Jia, Qiuyao
McGowin, Chris L.
Martin, David H.
TI Genetic Variation in the Complete MgPa Operon and Its Repetitive
Chromosomal Elements in Clinical Strains of Mycoplasma genitalium
SO PLOS ONE
LA English
DT Article
ID POLYMERASE CHAIN-REACTION; FRAGMENT LENGTH POLYMORPHISM; REAL-TIME PCR;
NONGONOCOCCAL URETHRITIS; AZITHROMYCIN TREATMENT; PNEUMONIAE;
RECOMBINATION; SPECIMENS; SEQUENCES; PROTEIN
AB Mycoplasma genitalium has been increasingly recognized as an important microbe not only because of its significant association with human genital tract diseases but also because of its utility as a model for studying the minimum set of genes necessary to sustain life. Despite its small genome, 4.7% of the total genome sequence is devoted to making the MgPa adhesin operon and its nine chromosomal repetitive elements (termed MgPars). The MgPa operon, along with 9 MgPars, is believed to play an important role in pathogenesis of M. genitalium infection and has also served as the main target for development of diagnostic tools. However, genetic variation in the complete MgPa operon and MgPars among clinical strains of M. genitalium has not been addressed. In this study we examined the genetic variation in the complete MgPa operon (approximately 8.5 kb) and full or partial MgPar sequences (0.4-2.6 kb) in 15 geographically diverse strains of M. genitalium. Extensive variation was present in four repeat regions of the MgPa operon (with homology to MgPars) among and within strains while the non-repeat regions (without homology to MgPars) showed low-level variation among strains and no variation within strains. MgPars showed significant variation among strains but were highly homogeneous within strains, supporting gene conversion as the likely recombination mechanism. When applying our sequence data to evaluate published MgPa operon-based diagnostic PCR assays and genotyping systems, we found that 11 of 19 primers contain up to 19 variable nucleotides and that the target for one of two typing systems is located in a hypervariable repeat region, suggesting the likelihood of false results with some of these assays. This study not only provides new insights into the role of the MgPa operon in the pathogenesis of M. genitalium infection but has important implications for the development of diagnostic tools.
C1 [Ma, Liang; Mancuso, Miriam; Jia, Qiuyao; McGowin, Chris L.; Martin, David H.] Louisiana State Univ, Infect Dis Sect, Dept Med, Hlth Sci Ctr, New Orleans, LA USA.
[Jensen, Jorgen S.] Statens Serum Inst, Mycoplasma Lab, DK-2300 Copenhagen, Denmark.
[Hamasuna, Ryoichi] Univ Occupat & Environm Hlth, Dept Urol, Yahatanishi Ku, Kitakyushu, Fukuoka 807, Japan.
RP Ma, LA (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
EM LMa1@lsuhsc.edu
RI Jensen, Jorgen/I-2917-2012;
OI Jensen, Jorgen Skov/0000-0002-7464-7435
FU Department of Defense [W81XWH-08-1-0676]; National Institutes of Health
[5 U19 AI061972]; Louisiana Vaccine Center; Louisiana State of Regents
[149752505J]
FX This work was supported by the Department of Defense (grant
W81XWH-08-1-0676), the Gulf South Sexually Transmitted
Infections/Topical Microbicide Cooperative Research Center grant from
the National Institutes of Health (grant 5 U19 AI061972), and the
Louisiana Vaccine Center and the South Louisiana Institute for
Infectious Disease Research sponsored by the Louisiana State of Regents
(grant 149752505J). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 36
TC 15
Z9 17
U1 0
U2 0
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 DEC 20
PY 2010
VL 5
IS 12
AR e15660
DI 10.1371/journal.pone.0015660
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 698EM
UT WOS:000285575200059
PM 21187921
ER
PT J
AU Ni, T
Tu, K
Wang, Z
Song, S
Wu, H
Xie, B
Scott, KC
Grewal, SI
Gao, YA
Zhu, J
AF Ni, Ting
Tu, Kang
Wang, Zhong
Song, Shen
Wu, Han
Xie, Bin
Scott, Kristin C.
Grewal, Shiv I.
Gao, Yuan
Zhu, Jun
TI The Prevalence and Regulation of Antisense Transcripts in
Schizosaccharomyces pombe
SO PLOS ONE
LA English
DT Article
ID BIDIRECTIONAL PROMOTERS; PERVASIVE TRANSCRIPTION; NUCLEOTIDE RESOLUTION;
ACTIVE PROMOTERS; HISTONE H2A.Z; YEAST GENOME; RNA-SEQ; GENES; MAPS;
IDENTIFICATION
AB A strand-specific transcriptome sequencing strategy, directional ligation sequencing or DeLi-seq, was employed to profile antisense transcriptome of Schizosaccharomyces pombe. Under both normal and heat shock conditions, we found that polyadenylated antisense transcripts are broadly expressed while distinct expression patterns were observed for protein-coding and non-coding loci. Dominant antisense expression is enriched in protein-coding genes involved in meiosis or stress response pathways. Detailed analyses further suggest that antisense transcripts are independently regulated with respect to their sense transcripts, and diverse mechanisms might be potentially involved in the biogenesis and degradation of antisense RNAs. Taken together, antisense transcription may have profound impacts on global gene regulation in S. pombe.
C1 [Ni, Ting; Tu, Kang; Song, Shen; Wu, Han; Scott, Kristin C.; Zhu, Jun] Duke Univ, Med Ctr, Inst Genome Sci & Policy, Durham, NC 27710 USA.
[Ni, Ting; Tu, Kang; Wu, Han; Zhu, Jun] NHLBI, Genet & Dev Biol Ctr, NIH, Bethesda, MD 20892 USA.
[Wang, Zhong] DOE Joint Genome Inst, Walnut Creek, CA USA.
[Xie, Bin; Gao, Yuan] Johns Hopkins Univ, Div Genom Epigenom & Bioinformat, Lieber Inst Brain Dev, Baltimore, MD USA.
[Gao, Yuan] Johns Hopkins Univ, Neuroregenerat & Stem Cell Biol Program, Inst Cell Engn, Baltimore, MD USA.
[Grewal, Shiv I.] NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Ni, T (reprint author), Duke Univ, Med Ctr, Inst Genome Sci & Policy, Durham, NC 27710 USA.
EM jun.zhu@nih.gov
RI Wang, Zhong/E-7897-2011; Gao, Yuan/E-1706-2011; Wu, Han/E-3455-2013
OI Wu, Han/0000-0002-3972-698X
FU Department of Defense [BC074085P1]; Susan G. Komen for the Cure
[KG081324]
FX This work was supported by Department of Defense (BC074085P1) and Susan
G. Komen for the Cure (KG081324) to J.Z. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 50
TC 33
Z9 34
U1 0
U2 10
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 DEC 20
PY 2010
VL 5
IS 12
AR e15271
DI 10.1371/journal.pone.0015271
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 698EM
UT WOS:000285575200029
PM 21187966
ER
PT J
AU Chun, KS
Lao, HC
Langenbach, R
AF Chun, Kyung-Soo
Lao, Huei-Chen
Langenbach, Robert
TI The Prostaglandin E-2 Receptor, EP2, Stimulates Keratinocyte
Proliferation in Mouse Skin by G Protein-dependent and
beta-Arrestin1-dependent Signaling Pathways
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID GROWTH-FACTOR RECEPTOR; BETA-ADRENERGIC-RECEPTOR; SRC FAMILY KINASES;
COUPLED RECEPTORS; EGF RECEPTOR; EPITHELIAL CARCINOGENESIS; PROSTANOID
RECEPTORS; TUMOR-DEVELOPMENT; KNOCKOUT MICE; ACTIVATION
AB The prostaglandin E-2 (PGE2) G protein-coupled receptor (GPCR), EP2, plays important roles in mouse skin tumor development (Chun, K. S., Lao, H. C., Trempus, C. S., Okada, M., and Langenbach, R. (2009) Carcinogenesis 30, 1620-1627). Because keratinocyte proliferation is essential for skin tumor development, EP2-mediated signaling pathways that contribute to keratinocyte proliferation were investigated. A single topical application of the EP2 agonist, butaprost, dose-dependently increased keratinocyte replication via activation of epidermal growth factor receptor (EGFR) and PKA signaling. Because GPCR-mediated activation of EGFR can involve the formation of a GPCR-beta-arrestin-Src signaling complex, the possibility of a beta-arrestin1-Src complex contributing to EP2-mediated signaling in keratinocytes was investigated. Butaprost induced beta-arrestin1-Src complex formation and increased both Src and EGFR activation. A role for beta-arrestin1 in EP2-mediated Src and EGFR activation was demonstrated by the observation that beta-arrestin1 deficiency significantly reduced Src and EGFR activation. In agreement with a beta-arrestin1-Src complex contributing to EGFR activation, Src and EGFR inhibition (PP2 and AG1478, respectively) indicated that Src was upstream of EGFR. Butaprost also induced the activation of Akt, ERK1/2, and STAT3, and both beta-arrestin1 deficiency and EGFR inhibition (AG1478 or gefitinib) decreased their activation. In addition to beta-arrestin1-dependent EGFR activation, butaprost increased PKA activation, as measured by phospho-GSK3 beta (p-GSK3 beta) and p-cAMP-response element-binding protein formation. PKA inhibition (H89 or R-P-adenosine-3',5'-cyclic monophosphorothioate (R-P-cAMPS)) decreased butaprost-induced cAMP-response element-binding protein and ERK activation but did not affect EGFR activation, whereas beta-arrestin1 deficiency decreased EGFR activation but did not affect butaprost-induced PKA activation, thus indicating that they were independent EP2-mediated pathways. Therefore, the results indicate that EP2 contributed to mouse keratinocyte proliferation by G protein-independent, beta-arrestin1- dependent activation of EGFR and G protein-dependent activation of PKA.
C1 [Chun, Kyung-Soo; Lao, Huei-Chen; Langenbach, Robert] NIEHS, NIH, Lab Toxicol & Pharmacol, Res Triangle Pk, NC 27709 USA.
RP Langenbach, R (reprint author), NIEHS, NIH, Lab Toxicol & Pharmacol, MD C4-09,POB 12233, Res Triangle Pk, NC 27709 USA.
EM langenb1@niehs.nih.gov
FU NIEHS/National Institutes of Health
FX This work was supported, in whole or in part, by the Intramural Research
Program of the NIEHS/National Institutes of Health.
NR 54
TC 25
Z9 25
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 DEC 17
PY 2010
VL 285
IS 51
BP 39672
EP 39681
DI 10.1074/jbc.M110.117689
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 692WB
UT WOS:000285185500011
PM 20959465
ER
PT J
AU Trzemecka, A
Jacewicz, A
Carver, GT
Drake, JW
Bebenek, A
AF Trzemecka, Anna
Jacewicz, Agata
Carver, Geraldine T.
Drake, John W.
Bebenek, Anna
TI Reversal of a Mutator Activity by a Nearby Fidelity-Neutral Substitution
in the RB69 DNA Polymerase Binding Pocket
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE Exo; Pol
ID REPLICATION FIDELITY; WILD-TYPE; BIOCHEMICAL BASIS; BASE SELECTIVITY;
BACTERIOPHAGE-T4; MUTANT; DISCRIMINATION; PROCESSIVITY; MECHANISMS;
MUTATIONS
AB Phage RB69 B-family DNA polymerase is responsible for the overall high fidelity of RB69 DNA synthesis Fidelity is compromised when conserved Tyr567, one of the residues that form the nascent polymerase base-pair binding pocket, is replaced by alanine The Y567A mutator mutant has an enlarged binding pocket and can incorporate and extend mispairs efficiently Ser565 is a nearby conserved residue that also contributes to the binding pocket, but a S565G replacement has only a small impact on DNA replication fidelity When Y567A and S565G replacements were combined, mutator activity was strongly decreased compared to that with Y567A replacement alone Analyses conducted both in vivo and in vitro revealed that, compared to Y567A replacement alone, the double mutant mainly reduced base substitution mutations and, to a lesser extent, frameshift mutations The decrease in mutation rates was not due to increased exonuclease activity Based on measurements of DNA binding affinity, mismatch insertion, and mismatch extension, we propose that the recovered fidelity of the double mutant may result, in part, from an increased dissociation of the enzyme from DNA, followed by the binding of the same or another polymerase molecule in either exonuclease mode or polymerase mode An additional antimutagenic factor may be a structural alteration in the polymerase binding pocket described in this article (C) 2010 Elsevier Ltd All rights reserved
C1 [Trzemecka, Anna; Jacewicz, Agata; Bebenek, Anna] Polish Acad Sci, Inst Biochem & Biophys, Dept Mol Biol, PL-02104 Warsaw, Poland.
[Carver, Geraldine T.; Drake, John W.] NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA.
RP Bebenek, A (reprint author), Polish Acad Sci, Inst Biochem & Biophys, Dept Mol Biol, Pawinskiego 5A, PL-02104 Warsaw, Poland.
FU National Institutes of Health, National Institute of Environmental
Health Sciences, USA [Z01ES061054]; Polish Ministry of Science and
Higher Education [N301014433]
FX We thank Bill Beard for providing Fig 9 and both Bill Beard and Mike
Murray for critical readings of the manuscript and Bill Konigsberg for
advice on the implications of his structural models This research was
supported, in part, by funds allocated to project number Z01ES061054 of
the Intramural Research Program of the National Institutes of Health,
National Institute of Environmental Health Sciences, USA, and by grant
N301014433 from the Polish Ministry of Science and Higher Education (to
A B)
NR 28
TC 7
Z9 8
U1 1
U2 4
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 DEC 17
PY 2010
VL 404
IS 5
BP 778
EP 793
DI 10.1016/j.jmb.2010.09.058
PG 16
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 699IT
UT WOS:000285657800004
PM 20950625
ER
PT J
AU Jang, H
Arce, FT
Ramachandran, S
Capone, R
Lal, R
Nussinov, R
AF Jang, Hyunbum
Arce, Fernando Teran
Ramachandran, Srinivasan
Capone, Ricardo
Lal, Ratnesh
Nussinov, Ruth
TI beta-Barrel Topology of Alzheimer's beta-Amyloid Ion Channels
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE toxic amyloid ion channels; beta-barrel; U-shaped motif; molecular
dynamics; simulations; atomic force microscopy
ID SOLID-STATE NMR; LIPID-BILAYERS; 3D STRUCTURE; ZN2+-SENSITIVE CHANNEL;
ALANINE DIPEPTIDE; CALCIUM-CHANNELS; PEPTIDE CHANNELS; OUTER-MEMBRANE;
PRION PROTEIN; SHEET BARRELS
AB Emerging evidence supports the ion channel mechanism for Alzheimer's disease pathophysiology wherein small beta-amyloid (A beta) oligomers insert into the cell membrane, forming toxic ion channels and destabilizing the cellular ionic homeostasis Solid-state NMR-based data of amyloid oligomers in solution indicate that they consist of a double-layered beta-sheets where each monomer folds into beta-strand-turn-beta-strand and the monomers are stacked atop each other In the membrane, A beta peptides are proposed to be beta-type structures Experimental structural data available from atomic force microscopy (AFM) imaging of A beta oligomers in membranes reveal heterogeneous channel morphologies Previously, we modeled the channels in a non-tilted organization, parallel with the cross-membrane normal Here, we modeled a beta-barrel-like organization beta-Barrels are common in transmembrane toxin pores, typically consisting of a monomeric chain forming a pore, organized in a single-layered beta-sheet with antiparallel beta-strands and a right-handed twist Our explicit solvent molecular dynamics simulations of a range of channel sizes and polymorphic turns and comparisons of these with AFM image dimensions support a beta-barrel channel organization Different from the transmembrane beta-barrels where the monomers are folded into a circular beta-sheet with antiparallel beta-strands stabihzed by the connecting loops, these A beta barrels consist of multimeric chains forming double beta-sheets with parallel beta-strands, where the strands of each monomer are connected by a turn Although the A beta barrels adopt the right-handed beta-sheet twist, the barrels still break into heterogeneous, loosely attached subunits, in good agreement with AFM images and previous modeling The subunits appear mobile, allowing unregulated, hence toxic, ion flux (C) 2010 Elsevier Ltd All rights reserved
C1 [Jang, Hyunbum; Nussinov, Ruth] Natl Canc Inst Frederick, Ctr Canc Res Nanobiol Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Arce, Fernando Teran; Ramachandran, Srinivasan; Capone, Ricardo; Lal, Ratnesh] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA.
[Arce, Fernando Teran; Ramachandran, Srinivasan; Capone, Ricardo; Lal, Ratnesh] Univ Calif San Diego, Dept Mech & Aerosp Engn, La Jolla, CA 92093 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Mol Genet, IL-69978 Tel Aviv, Israel.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Biochem, IL-69978 Tel Aviv, Israel.
RP Nussinov, R (reprint author), Natl Canc Inst Frederick, Ctr Canc Res Nanobiol Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
RI Capone, Ricardo/D-1943-2010
OI Capone, Ricardo/0000-0002-7327-9837
FU National Cancer Institute, National Institutes of Health (NIH)
[HHSN261200800001E]; National Cancer Institute Center for Cancer
Research, NIH; National Institute on Aging, NIH
FX This project has been funded m whole or m part with federal funds from
the National Cancer Institute, National Institutes of Health (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 U S Government This
research was supported in part by the Intramural Research Program of the
National Cancer Institute Center for Cancer Research, NIH This research
was also supported by the National Institute on Aging, NIH, extramural
program (R L) All simulations had been performed using the
high-performance computational facilities of the Biowulf PC/Linux
cluster at the NIH
NR 92
TC 54
Z9 55
U1 4
U2 31
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 DEC 17
PY 2010
VL 404
IS 5
BP 917
EP 934
DI 10.1016/j.jmb.2010.10.025
PG 18
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 699IT
UT WOS:000285657800014
PM 20970427
ER
PT J
AU Mitchell, K
Bates, BD
Keller, JM
Lopez, M
Scholl, L
Navarro, J
Madian, N
Haspel, G
Nemenov, MI
Iadarola, MJ
AF Mitchell, Kendall
Bates, Brian D.
Keller, Jason M.
Lopez, Matthew
Scholl, Lindsey
Navarro, Julia
Madian, Nicholas
Haspel, Gal
Nemenov, Michael I.
Iadarola, Michael J.
TI Ablation of rat TRPV1-expressing Adelta/C-fibers with resiniferatoxin:
analysis of withdrawal behaviors, recovery of function and molecular
correlates
SO MOLECULAR PAIN
LA English
DT Article
ID PRIMARY SOMATOSENSORY CORTEX; VANILLOID RECEPTOR TRPV1; DORSAL-ROOT
GANGLION; INFRARED DIODE-LASER; SENSORY NEURONS; SPINAL-CORD;
GENE-EXPRESSION; CONDUCTION-VELOCITY; CAPSAICIN RECEPTOR; PRIMARY
AFFERENT
AB Background: Ablation of TRPV1-expressing nociceptive fibers with the potent capsaicin analog resiniferatoxin (RTX) results in long lasting pain relief. RTX is particularly adaptable to focal application, and the induced chemical axonopathy leads to analgesia with a duration that is influenced by dose, route of administration, and the rate of fiber regeneration. TRPV1 is expressed in a subpopulation of unmyelinated C-and lightly myelinated Adelta fibers that detect changes in skin temperature at low and high rates of noxious heating, respectively. Here we investigate fiber-type specific behaviors, their time course of recovery and molecular correlates of axon damage and nociception using infrared laser stimuli following an RTX-induced peripheral axonopathy.
Results: RTX was injected into rat hind paws (mid-plantar) to produce thermal hypoalgesia. An infrared diode laser was used to stimulate Adelta fibers in the paw with a small-diameter (1.6 mm), high-energy, 100 msec pulse, or C-fibers with a wide-diameter (5 mm), long-duration, low-energy pulse. We monitored behavioral responses to indicate loss and regeneration of fibers. At the site of injection, responses to C-fiber stimuli were significantly attenuated for two weeks after 5 or 50 ng RTX. Responses to Adelta stimuli were significantly attenuated for two weeks at the highest intensity stimulus, and for 5 weeks to a less intense Adelta stimulus. Stimulation on the toe, a site distal to the injection, showed significant attenuation of Adelta responses for 7-8 weeks after 5 ng, or 9-10 weeks after 50 ng RTX. In contrast, responses to C-fiber stimuli exhibited basically normal responses at 5 weeks after RTX. During the period of fiber loss and recovery, molecular markers for nerve regeneration (ATF3 and galanin) are upregulated in the dorsal root ganglia (DRG) when behavior is maximally attenuated, but markers of nociceptive activity (c-Fos in spinal cord and MCP-1 in DRG), although induced immediately after RTX treatment, returned to normal.
Conclusion: Behavioral recovery following peripheral RTX treatment is linked to regeneration of TRPV1-expressing Adelta and C-fibers and sustained expression of molecular markers. Infrared laser stimulation is a potentially valuable tool for evaluating the behavioral role of Adelta fibers in pain and pain control.
C1 [Mitchell, Kendall; Bates, Brian D.; Keller, Jason M.; Lopez, Matthew; Scholl, Lindsey; Navarro, Julia; Madian, Nicholas; Iadarola, Michael J.] Natl Inst Dent & Craniofacial Res, Neurobiol & Pain Therapeut Sect, Lab Sensory Biol, NIH, Bethesda, MD USA.
[Nemenov, Michael I.] Stanford Univ, Dept Anesthesia, Palo Alto, CA 94304 USA.
[Nemenov, Michael I.] Lasmed LLC, Mountain View, CA USA.
[Haspel, Gal] NINDS, Neural Control Lab, Sect Dev Neurobiol, NIH, Bethesda, MD 20892 USA.
RP Iadarola, MJ (reprint author), Natl Inst Dent & Craniofacial Res, Neurobiol & Pain Therapeut Sect, Lab Sensory Biol, NIH, Bethesda, MD USA.
EM miadarola@dir.nidcr.nih.gov
RI Nemenov, Mike/I-7477-2012;
OI Haspel, Gal/0000-0001-6701-697X
FU NIDCR, NIH, DHHS; NIH [DE015731, NS046951]
FX This research was supported by the Intramural Research Program, NIDCR,
NIH, DHHS. NIH grants DE015731 and NS046951 are gratefully acknowledged.
We thanks Dr Daphne Soares for the loan of high speed camera system.
NR 57
TC 27
Z9 28
U1 0
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1744-8069
J9 MOL PAIN
JI Mol. Pain
PD DEC 17
PY 2010
VL 6
AR 94
DI 10.1186/1744-8069-6-94
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA 705GE
UT WOS:000286116100001
PM 21167052
ER
PT J
AU Chadwick, W
Zhou, Y
Park, SS
Wang, LY
Mitchell, N
Stone, MD
Becker, KG
Martin, B
Maudsley, S
AF Chadwick, Wayne
Zhou, Yu
Park, Sung-Soo
Wang, Liyun
Mitchell, Nicholas
Stone, Matthew D.
Becker, Kevin G.
Martin, Bronwen
Maudsley, Stuart
TI Minimal Peroxide Exposure of Neuronal Cells Induces Multifaceted
Adaptive Responses
SO PLOS ONE
LA English
DT Article
ID HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; CHROMATIN PROTEIN HMGB2; GROWTH-FACTOR
RECEPTOR; ALZHEIMERS-DISEASE; OXIDATIVE STRESS; PREMATURE SENESCENCE;
NEUROTROPHIC FACTOR; LIFE-SPAN; PARKINSONS-DISEASE; MESSENGER-RNA
AB Oxidative exposure of cells occurs naturally and may be associated with cellular damage and dysfunction. Protracted low level oxidative exposure can induce accumulated cell disruption, affecting multiple cellular functions. Accumulated oxidative exposure has also been proposed as one of the potential hallmarks of the physiological/pathophysiological aging process. We investigated the multifactorial effects of long-term minimal peroxide exposure upon SH-SY5Y neural cells to understand how they respond to the continued presence of oxidative stressors. We show that minimal protracted oxidative stresses induce complex molecular and physiological alterations in cell functionality. Upon chronic exposure to minimal doses of hydrogen peroxide, SH-SY5Y cells displayed a multifactorial response to the stressor. To fully appreciate the peroxide-mediated cellular effects, we assessed these adaptive effects at the genomic, proteomic and cellular signal processing level. Combined analyses of these multiple levels of investigation revealed a complex cellular adaptive response to the protracted peroxide exposure. This adaptive response involved changes in cytoskeletal structure, energy metabolic shifts towards glycolysis and selective alterations in transmembrane receptor activity. Our analyses of the global responses to chronic stressor exposure, at multiple biological levels, revealed a viable neural phenotype in-part reminiscent of aged or damaged neural tissue. Our paradigm indicates how cellular physiology can subtly change in different contexts and potentially aid the appreciation of stress response adaptations.
C1 [Chadwick, Wayne; Zhou, Yu; Park, Sung-Soo; Wang, Liyun; Stone, Matthew D.; Maudsley, Stuart] NIA, Receptor Pharmacol Unit, NIH, Baltimore, MD 21224 USA.
[Mitchell, Nicholas] St Bonaventure Univ, Dept Biol, St Bonaventure, NY 14778 USA.
[Becker, Kevin G.] NIA, Gene Express & Genom Unit, Res Resources Branch, NIH, Baltimore, MD 21224 USA.
[Martin, Bronwen] NIA, Metab Unit, NIH, Baltimore, MD 21224 USA.
RP Chadwick, W (reprint author), NIA, Receptor Pharmacol Unit, NIH, Baltimore, MD 21224 USA.
EM maudsleyst@mail.nih.gov
RI Zhou, Yu/M-7975-2014;
OI Becker, Kevin/0000-0002-6794-6656
FU National Institute on Aging
FX This research was supported by the Intramural Research Program of the
National Institute on Aging. The funding authority had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 156
TC 24
Z9 24
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 DEC 17
PY 2010
VL 5
IS 12
AR e14352
DI 10.1371/journal.pone.0014352
PG 26
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 698DS
UT WOS:000285572900002
PM 21179406
ER
PT J
AU Sebbane, F
Jarrett, C
Gardner, D
Long, D
Hinnebusch, BJ
AF Sebbane, Florent
Jarrett, Clayton
Gardner, Donald
Long, Daniel
Hinnebusch, B. Joseph
TI Role of the Yersinia pestis Yersiniabactin Iron Acquisition System in
the Incidence of Flea-Borne Plague
SO PLOS ONE
LA English
DT Article
ID PASTEURELLA PESTIS; PIGMENTATION; TRANSMISSION; DELETION
AB Plague is a flea-borne zoonosis caused by the bacterium Yersinia pestis. Y. pestis mutants lacking the yersiniabactin (Ybt) siderophore-based iron transport system are avirulent when inoculated intradermally but fully virulent when inoculated intravenously in mice. Presumably, Ybt is required to provide sufficient iron at the peripheral injection site, suggesting that Ybt would be an essential virulence factor for flea-borne plague. Here, using a flea-to-mouse transmission model, we show that a Y. pestis strain lacking the Ybt system causes fatal plague at low incidence when transmitted by fleas. Bacteriology and histology analyses revealed that a Ybt-negative strain caused only primary septicemic plague and atypical bubonic plague instead of the typical bubonic form of disease. The results provide new evidence that primary septicemic plague is a distinct clinical entity and suggest that unusual forms of plague may be caused by atypical Y. pestis strains.
C1 [Sebbane, Florent] Inst Pasteur, Ctr Infect & Immun Lille, Equipe Peste & Yersinia Pestis, F-59019 Lille, France.
[Sebbane, Florent] INSERM, U1019, F-59045 Lille, France.
[Sebbane, Florent] Inst Pasteur, Ctr Immunol & Biol Parasitaire, CNRS, UMR8204, F-59019 Lille, France.
[Sebbane, Florent] Univ Lille Nord France, Lille, France.
[Sebbane, Florent] Ctr Infect & Immun Lille, UDSL, Lille, France.
[Jarrett, Clayton; Hinnebusch, B. Joseph] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT USA.
[Jarrett, Clayton; Gardner, Donald; Long, Daniel; Hinnebusch, B. Joseph] NIAID, Vet Pathol Sect, Rocky Mt Labs, NIH, Hamilton, MT USA.
RP Sebbane, F (reprint author), Inst Pasteur, Ctr Infect & Immun Lille, Equipe Peste & Yersinia Pestis, F-59019 Lille, France.
EM florent.sebbane@inserm.fr
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health; Institut National de
la Sante et de la Recherche Medicale
FX This work was supported by the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health; and Institut National de la Sante et de la Recherche Medicale.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 19
TC 14
Z9 15
U1 0
U2 6
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 DEC 17
PY 2010
VL 5
IS 12
AR e14379
DI 10.1371/journal.pone.0014379
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 698DS
UT WOS:000285572900011
PM 21179420
ER
PT J
AU Waxman, AJ
Mink, PJ
Devesa, SS
Anderson, WF
Weiss, BM
Kristinsson, SY
McGlynn, KA
Landgren, O
AF Waxman, Adam J.
Mink, Pamela J.
Devesa, Susan S.
Anderson, William F.
Weiss, Brendan M.
Kristinsson, Sigurdur Y.
McGlynn, Katherine A.
Landgren, Ola
TI Racial disparities in incidence and outcome in multiple myeloma: a
population-based study
SO BLOOD
LA English
DT Article
ID UNDETERMINED SIGNIFICANCE MGUS; STEM-CELL TRANSPLANTATION; MONOCLONAL
GAMMOPATHY; SOCIOECONOMIC-STATUS; PLUS DEXAMETHASONE; AFRICAN-AMERICAN;
UNITED-STATES; SURVIVAL; RACE; CANCER
AB Multiple myeloma (MM) is the most common hematologic malignancy in blacks. Some prior studies suggest inferior survival in blacks; others suggest similar survival. Using the original 9 Surveillance, Epidemiology, and End Results registries, we conducted a large-scale population-based study including 5798 black and 28 939 white MM patients diagnosed 1973-2005, followed through 2006. Age-adjusted incidence rates, disease-specific survival, and relative survival rates were calculated by race, age, and time period of diagnosis. Mean age at diagnosis was 65.8 and 69.8 years for blacks and whites, respectively (P < .001). Incidence among blacks was m twice that among whites; this disparity was greater among patients < 50 years (P = .002). Over the entire study period, disease-specific and relative survival rates were higher in blacks than whites (P < .001). For whites, 5-year relative survival rates increased significantly 1973-1993 to 1994-1998 (26.3% to 30.8%; P < .001) and 1994-1998 to 1999-2005 (30.8% to 35.0%; P = .004). Survival improvements among blacks were smaller and nonsignificant (1973-1993 to 1999-2005: 31.0% to 34.1%; P = .07). We found (1) a younger age of onset among blacks; (2) better survival in blacks 1973-2005; and (3) significant survival improvement among whites over time, with smaller, nonsignificant change seen among blacks, possibly due to unequal access to and/or disparate responsiveness to novel therapies. (Blood. 2010; 116(25): 5501-5506)
C1 [Landgren, Ola] NCI, NIH, Ctr Canc Res, Med Oncol Branch, Bethesda, MD 20892 USA.
[Mink, Pamela J.] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA.
[Devesa, Susan S.; Anderson, William F.; McGlynn, Katherine A.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Weiss, Brendan M.] Walter Reed Army Med Ctr, Washington, DC 20307 USA.
[Kristinsson, Sigurdur Y.] Karolinska Univ Hosp & Inst, Stockholm, Sweden.
RP Landgren, O (reprint author), NCI, NIH, Ctr Canc Res, Med Oncol Branch, 9000 Rockville Pike,Bldg 10,Rm 13N240, Bethesda, MD 20892 USA.
EM landgreo@mail.nih.gov
RI Kristinsson, Sigurdur /M-2910-2015
OI Kristinsson, Sigurdur /0000-0002-4964-7476
FU NCI of the National Institutes of Health (NIH); NIH; Foundation for NIH;
Pfizer Inc
FX This work was supported by the Intramural Research Program of the NCI of
the National Institutes of Health (NIH).; The authors declare no
competing financial interests. A.J.W. is a member of the NIH Clinical
Research Training Program, which is funded jointly by the NIH and the
Foundation for NIH (in part by a grant from Pfizer Inc).
NR 48
TC 88
Z9 89
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 DEC 16
PY 2010
VL 116
IS 25
BP 5501
EP 5506
DI 10.1182/blood-2010-07-298760
PG 6
WC Hematology
SC Hematology
GA 695PE
UT WOS:000285383900013
PM 20823456
ER
PT J
AU Moir, S
Buckner, CM
Ho, J
Wang, W
Chen, J
Waldner, AJ
Posada, JG
Kardava, L
O'Shea, MA
Kottilil, S
Chun, TW
Proschan, MA
Fauci, AS
AF Moir, Susan
Buckner, Clarisa M.
Ho, Jason
Wang, Wei
Chen, Jenny
Waldner, Amy J.
Posada, Jacqueline G.
Kardava, Lela
O'Shea, Marie A.
Kottilil, Shyam
Chun, Tae-Wook
Proschan, Michael A.
Fauci, Anthony S.
TI B cells in early and chronic HIV infection: evidence for preservation of
immune function associated with early initiation of antiretroviral
therapy
SO BLOOD
LA English
DT Article
ID INFLUENZA VACCINATION; ANTIBODY-RESPONSE; MEMORY; INDIVIDUALS; DISEASE;
IMMUNIZATION; VIRUS; HAART; HYPERGAMMAGLOBULINEMIA; SUBPOPULATIONS
AB Characterization of lymphocytes including B cells during early versus chronic HIV infection is important for understanding the impact of chronic viremia on immune cell function. In this setting, we investigated B cells before and after reduction of HIV plasma viremia by antiretroviral therapy (ART). At baseline, peripheral blood B-cell counts were significantly lower in both early and chronic HIV-infected individuals compared with uninfected controls. Similar to CD4(+) but not CD8(+) T cells, B-cell numbers in both groups increased significantly after ART. At baseline, B cells of early HIV-infected individuals were composed of a higher percentage of plasmablasts and resting memory B cells compared with chronic HIV-infected individuals whose B cells were composed of a higher percentage of immature/transitional and exhausted B cells compared with their early infection counterparts. At 1 year after ART, the percentage of resting memory B cells remained higher in early compared with chronic HIV-infected individuals. This difference translated into a better functional profile in that memory B-cell responses to HIV and non-HIV antigens were superior in early-compared with chronic-treated HIV infected individuals. These findings provide new insights on B cells in HIV infection and how early initiation of ART may prevent irreversible immune system damage. (Blood. 2010; 116(25): 5571-5579)
C1 [Moir, Susan; Buckner, Clarisa M.; Ho, Jason; Wang, Wei; Chen, Jenny; Waldner, Amy J.; Posada, Jacqueline G.; Kardava, Lela; O'Shea, Marie A.; Kottilil, Shyam; Chun, Tae-Wook; Fauci, Anthony S.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Chen, Jenny] Howard Hughes Med Inst, NIH Res Scholar Program, Chevy Chase, MD USA.
[Proschan, Michael A.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
RP Moir, S (reprint author), NIAID, Immunoregulat Lab, NIH, 9000 Rockville Pike,Bldg 10,Rm 6A02, Bethesda, MD 20892 USA.
EM smoir@niaid.nih.gov
FU NIAID, NIH
FX This work was supported by the Intramural Research Program of NIAID,
NIH.
NR 49
TC 102
Z9 107
U1 1
U2 12
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 DEC 16
PY 2010
VL 116
IS 25
BP 5571
EP 5579
DI 10.1182/blood-2010-05-285528
PG 9
WC Hematology
SC Hematology
GA 695PE
UT WOS:000285383900020
PM 20837780
ER
PT J
AU Guech-Ongey, M
Simard, EP
Anderson, WF
Engels, EA
Bhatia, K
Devesa, SS
Mbulaiteye, SM
AF Guech-Ongey, Mercy
Simard, Edgar P.
Anderson, William F.
Engels, Eric A.
Bhatia, Kishor
Devesa, Susan S.
Mbulaiteye, Sam M.
TI AIDS-related Burkitt lymphoma in the United States: what do age and CD4
lymphocyte patterns tell us about etiology and/or biology?
SO BLOOD
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; INDUCED CYTIDINE DEAMINASE; DISEASE;
CANCER; IMMUNOSUPPRESSION; EXPRESSION; INFECTION; DIAGNOSIS; FEATURES;
LINKAGE
AB Trimodal or bimodal age-specific incidence rates for Burkitt lymphoma (BL) were observed in the United States general population, but the role of immunosuppression could not be excluded. Incidence rates, rate ratios, and 95% confidence intervals for BL and other non-Hodgkin lymphoma (NHL), by age and CD4 lymphocyte count categories, were estimated using Poisson regression models using data from the United States HIV/AIDS Cancer Match study (1980-2005). BL incidence was 22 cases per 100 000 person-years and 586 for non-BL NHL. Adjusted BL incidence rate ratio among males was 1.6x that among females and among non-Hispanic blacks, 0.4x that among non-Hispanic whites, but unrelated to HIV-transmission category. Non-BL NHL incidence increased from childhood to adulthood; in contrast, 2 age-specific incidence peaks during the pediatric and adult/geriatric years were observed for BL. Non-BL NHL incidence rose steadily with decreasing CD4 lymphocyte counts; in contrast, BL incidence was lowest among people with <= 50 CD4 lymphocytes/mu L versus those with >= 250 CD4 lymphocytes/mu L (incidence rate ratio 0.3 [95% confidence interval = 0.2-0.6]). The bimodal peaks for BL, in contrast to non-BL NHL, suggest effects of noncumulative risk factors at different ages. Under-ascertainment or biological reasons may account for BL deficit at low CD4 lymphocyte counts. (Blood. 2010; 116(25): 5600-5604)
C1 [Guech-Ongey, Mercy; Simard, Edgar P.; Engels, Eric A.; Bhatia, Kishor; Mbulaiteye, Sam M.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Anderson, William F.; Devesa, Susan S.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Guech-Ongey, M (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,Execut Plaza S,Rm 7078, Rockville, MD 20852 USA.
EM guechome@mail.nih.gov
FU National Cancer Institute, National Institutes of Health, Department of
Health and Human Services [N02-CP-31003, N01-CO-12400]
FX This work was supported by the Intramural Research Program of the
National Cancer Institute (contracts N02-CP-31003 and N01-CO-12400),
National Institutes of Health, Department of Health and Human Services.
NR 40
TC 40
Z9 44
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 DEC 16
PY 2010
VL 116
IS 25
BP 5600
EP 5604
DI 10.1182/blood-2010-03-275917
PG 5
WC Hematology
SC Hematology
GA 695PE
UT WOS:000285383900023
PM 20813897
ER
PT J
AU Li, J
Maruyama, T
Zhang, P
Konkel, JE
Hoffman, V
Zamarron, B
Chen, WJ
AF Li, Jun
Maruyama, Takashi
Zhang, Pin
Konkel, Joanne E.
Hoffman, Victoria
Zamarron, Brian
Chen, WanJun
TI Mutation of inhibitory helix-loop-helix protein Id3 causes gamma delta
T-cell lymphoma in mice
SO BLOOD
LA English
DT Article
ID TRANSCRIPTION FACTOR FOXP3; OF-THE-LITERATURE; SJOGRENS-SYNDROME;
KNOCKOUT MICE; ACTIVATION; LINEAGE; GROWTH
AB Human gamma delta T-cell lymphoma is a rare clinicopathologic entity with aggressive course and poor prognosis. The etiology and pathogenesis of gamma delta T-cell lymphoma is unknown. We show here that mice with deficiency in inhibitory helix-loop-helix protein Id3 (Id3(-/-)) developed gamma delta T-cell lymphoma that resembled human gamma delta T-cell lymphoma. The Id3(-/-) mice with lymphoma showed splenomegaly, hepatomegaly, and lymphadenopathy with involvement of bone marrow, thymus, kidney, and lungs between 6 and 15 months of age. Phenotypic analysis revealed that lymphomatous cells were cluster of differentiation (CD)3(+), gamma delta T-cell receptor (TCR)(+), and gamma delta TCR(-), and expressed CD8(+)CD4(-), CD4(+)CD8(-), or a mixture of the two. Id3(-/-) gamma delta T-cell lymphoma used predominantly V gamma 1.1, some V gamma 3, yet no V gamma 2 TCR, and some showed increased levels of the oncogene c-Myc. Strikingly, adoptive transfer of the gamma delta T-cell lymphoma into syngeneic Rag1(-/-) mice resulted in aggressive gamma delta T-cell lymphoma, identical to the Id3(-/-) donor. Thus, our data demonstrate that Id3 regulates the development of gamma delta T-cell lymphoma in mice, raising a possibility of Id3 gene mutation in human gamma delta T-cell lymphoma. Our model will provide a tool for studying the molecular mechanisms and development of human gamma delta T-cell lymphoma. (Blood. 2010; 116(25): 5615-5621)
C1 [Li, Jun; Maruyama, Takashi; Zhang, Pin; Konkel, Joanne E.; Zamarron, Brian; Chen, WanJun] NIDCR, MIU, Oral Infect & Immun Branch, Bethesda, MD 20892 USA.
[Hoffman, Victoria] NIH, Diagnost & Res Serv Branch, Div Vet Resources, Bethesda, MD 20892 USA.
RP Chen, WJ (reprint author), NIDCR, MIU, Oral Infect & Immun Branch, Bldg 30,Rm 304,30 Convent Dr, Bethesda, MD 20892 USA.
EM wchen@mail.nih.gov
RI Li, Jun/N-6267-2015
FU National Institutes of Health, National Institute of Dental and
Craniofacial Research
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Dental and
Craniofacial Research.
NR 30
TC 16
Z9 16
U1 0
U2 0
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD DEC 16
PY 2010
VL 116
IS 25
BP 5615
EP 5621
DI 10.1182/blood-2010-03-274506
PG 7
WC Hematology
SC Hematology
GA 695PE
UT WOS:000285383900025
PM 20852128
ER
PT J
AU Szabova, L
Son, MY
Shi, J
Sramko, M
Yamada, SS
Swaim, WD
Zerfas, P
Kahan, S
Holmbeck, K
AF Szabova, Ludmila
Son, Mee-Young
Shi, Joanne
Sramko, Marek
Yamada, Susan S.
Swaim, William D.
Zerfas, Patricia
Kahan, Stacie
Holmbeck, Kenn
TI Membrane-type MMPs are indispensable for placental labyrinth formation
and development
SO BLOOD
LA English
DT Article
ID MATRIX METALLOPROTEINASES; EXTRACELLULAR-MATRIX; CATHEPSIN PROTEASES;
MOUSE PLACENTA; MT1-MMP; EXPRESSION; IMPLANTATION; DISEASE;
DECIDUALIZATION; ANGIOGENESIS
AB The membrane-type matrix metalloproteinases (MT-MMPs) are essential for pericellular matrix remodeling in late stages of development, as well as in growth and tissue homeostasis in postnatal life. Although early morphogenesis is perceived to involve substantial tissue remodeling, the roles of MT-MMPs in these processes are only partially characterized. Here we explore the functions of 2 prominently expressed MT-MMPs, MT1-MMP and MT2-MMP, and describe their roles in the process of placental morphogenesis. The fetal portion of the placenta, in particular the labyrinth (LA), displays strong overlapping expression of MT1-MMP and MT2-MMP, which is critical for syncytiotrophoblast formation and in turn for fetal vessels. Disruption of trophoblast syncytium formation consequently leads to developmental arrest with only a few poorly branched fetal vessels entering the LA causing embryonic death at embryonic day 11.5. Through knockdown of MMP expression, we demonstrate that either MT1-MMP or MT2-MMP is crucial specifically during development of the LA. In contrast, knockdown of MT-MMP activity after LA formation is compatible with development to term and postnatal life. Taken together these data identify essential but interchangeable roles for MT1-MMP or MT2-MMP in placental vasculogenesis and provide the first example of selective temporal and spatial MMP activity required for development of the mouse embryo. (Blood. 2010;116(25):5752-5761)
C1 [Szabova, Ludmila; Son, Mee-Young; Shi, Joanne; Sramko, Marek; Yamada, Susan S.; Kahan, Stacie; Holmbeck, Kenn] Natl Inst Dent & Craniofacial Res, Matrix Metalloproteinase Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA.
[Swaim, William D.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA.
[Zerfas, Patricia] NIH, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA.
RP Holmbeck, K (reprint author), Natl Inst Dent & Craniofacial Res, Matrix Metalloproteinase Unit, Craniofacial & Skeletal Dis Branch, NIH, Bldg 30,Rm 125,30 Convent Dr,MSC 4380, Bethesda, MD 20892 USA.
EM kenn.holmbeck@nih.gov
FU Division of Intramural Research, National Institutes of Health; Korea
Science and Engineering Foundation
FX This study was supported by the Division of Intramural Research, NIDCR
of the Intramural Research Program, National Institutes of Health. M.S.
was supported in part by postdoctoral fellowship funds from the Korea
Science and Engineering Foundation.
NR 33
TC 16
Z9 16
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 DEC 16
PY 2010
VL 116
IS 25
BP 5752
EP 5761
DI 10.1182/blood2009-10-249847
PG 10
WC Hematology
SC Hematology
GA 695PE
UT WOS:000285383900041
PM 20858856
ER
PT J
AU Feng, CG
Sher, A
AF Feng, Carl G.
Sher, Alan
TI Parasites Paralyze Cellular Host Defense System to Promote Virulence
SO CELL HOST & MICROBE
LA English
DT Editorial Material
ID TOXOPLASMA-GONDII; PARASITOPHOROUS VACUOLE; GTPASES
AB To promote their survival, intracellular pathogens must confront microbicidal activities induced by interferons. In this issue of Cell Host & Microbe, Fentress et al. show that Toxoplasma gondii evades intracellular killing by deploying a virulence determinant, ROP18, which acts by directly phosphorylating and disabling an IFN-gamma-inducible immunity-related GTPase involved in pathogen clearance.
C1 [Feng, Carl G.; Sher, Alan] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Feng, CG (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
EM cfeng@niaid.nih.gov
FU Intramural NIH HHS [Z01 AI000579-19]
NR 11
TC 1
Z9 1
U1 0
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1931-3128
J9 CELL HOST MICROBE
JI Cell Host Microbe
PD DEC 16
PY 2010
VL 8
IS 6
BP 463
EP 464
DI 10.1016/j.chom.2010.11.012
PG 2
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 721HO
UT WOS:000287344400001
PM 21147459
ER
PT J
AU Bergman, C
Kashiwaya, Y
Veech, RL
AF Bergman, Christian
Kashiwaya, Yoshihiro
Veech, Richard L.
TI The Effect of pH and Free Mg2+ on ATP Linked Enzymes and the Calculation
of Gibbs Free Energy of ATP Hydrolysis
SO JOURNAL OF PHYSICAL CHEMISTRY B
LA English
DT Article
ID NICOTINAMIDE-ADENINE DINUCLEOTIDE; EQUILIBRIUM-CONSTANTS; RAT LIVER;
PHYSIOLOGICAL CONDITIONS; ADENOSINE-TRIPHOSPHATE; IONIC-STRENGTH; FREE
MAGNESIUM; CITRATE LYASE; REDOX STATES; PHOSPHATE
AB The apparent equilibrium constants, K', of biochemical reactions containing substrates which bind [Mg2+] unequally can be significantly altered by changes in free intracellular [Mg2+]. Intracellular free [Mg2+] can be estimated by measurements of [citrate]/[isocitrate], a ratio known to vary with tissue free [Mg2+]. The combined equilibrium constant for glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, and triose phosphate isomerase for the three reactions (K'(GG-TPI)) was corrected using new binding constants for dihydroxyacetone-phosphate and 3-phosphoglycerate. The result of this calculation is demonstrated in the calculation of the free energy of ATP hydrolysis. In addition, the dependence of the equilibrium constant for the glutamine synthetase reaction on pH and free [Mg2+] was demonstrated. Furthermore, a theory linking the Delta G' value of mitochondria] complex I-II and the cytosolic Delta G' value of ATP hydrolysis is discussed with evidence from previous publications.
C1 [Bergman, Christian; Kashiwaya, Yoshihiro; Veech, Richard L.] NIAAA, LMC, NIH, DHHS, Bethesda, MD 20892 USA.
RP Veech, RL (reprint author), NIAAA, LMC, NIH, DHHS, 5625 Fishers Lane,Rm 2S-28, Bethesda, MD 20892 USA.
EM HUrveech@mail.nih.govUH
RI Bergman, Christian/D-8680-2012
NR 57
TC 7
Z9 7
U1 3
U2 22
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 DEC 16
PY 2010
VL 114
IS 49
BP 16137
EP 16146
DI 10.1021/jp105723r
PG 10
WC Chemistry, Physical
SC Chemistry
GA 690GO
UT WOS:000284990700013
PM 20866109
ER
PT J
AU Yin, H
Feng, GG
Clore, GM
Hummer, G
Rasaiah, JC
AF Yin, Hao
Feng, Guogang
Clore, G. Marius
Hummer, Gerhard
Rasaiah, Jayendran C.
TI Water in the Polar and Nonpolar Cavities of the Protein Interleukin-1
beta
SO JOURNAL OF PHYSICAL CHEMISTRY B
LA English
DT Article
ID HIGH-PRESSURE CRYSTALLOGRAPHY; MOLECULAR-DYNAMICS; BOUND WATER;
3-DIMENSIONAL STRUCTURE; HYDROPHOBIC CAVITY; CRYSTAL-STRUCTURE;
DISORDERED WATER; NMR-SPECTROSCOPY; AQUEOUS-SOLUTION; FREE-ENERGIES
AB Water in the protein interior serves important structural and functional roles and is also increasingly recognized as a relevant factor in drug binding. The nonpolar cavity in the protein interleulcin-l beta has been reported to be filled by water on the basis of some experiments and simulations and to be empty on the basis of others. Here we study the thermodynamics of filling the central nonpolar cavity and the four polar cavities of interleukin-1 beta by molecular dynamics simulation. We use different water models (TIP3P and SPC/E) and protein force fields (amber94 and amber03) to calculate the semigrand partition functions term by term that quantify the hydration equilibria. We consistently find that water in the central nonpolar cavity is thermodynamically unstable, independent of force field and water model. The apparent reason is the relatively small size of the cavity, with a volume less than 80 similar to angstrom(3). Our results are consistent with the most recent X-ray crystallographic and simulation studies but disagree with an earlier interpretation of nuclear magnetic resonance (NMR) experiments probing protein water interactions. We show that, at least semiquantitatively, the measured nuclear Overhauser effects indicating the proximity of water to the methyl groups lining the nonpolar cavity can, in all likelihood, be attributed to interactions with buried and surface water molecules near the cavity. The same methods applied to determine the occupancy of the polar cavities show that they are filled by the same number of water molecules observed in crystallography, thereby validating the theoretical and simulation methods used to study the water occupancy in the nonpolar protein cavity.
C1 [Clore, G. Marius; Hummer, Gerhard] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Yin, Hao; Feng, Guogang; Rasaiah, Jayendran C.] Univ Maine, Dept Chem, Orono, ME 04469 USA.
RP Hummer, G (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM Gerhard.Hummer@nih.gov; rasaiah@maine.edu
RI Clore, G. Marius/A-3511-2008; Hummer, Gerhard/A-2546-2013
OI Clore, G. Marius/0000-0003-3809-1027; Hummer,
Gerhard/0000-0001-7768-746X
FU Chemistry Division of the National Science Foundation [CHE 0549187, CHE
9961336]; NIDDK, NIH
FX G.F., FI.Y., and J.C.R. were supported by grants (CHE 0549187 and CHE
9961336) from the Chemistry Division of the National Science Foundation
and generous allocations of time from the University of Maine
supercomputer center. G.M.C. and G.H. are supported by the Intramural
Research Program of the NIDDK, NIH and acknowledge computer resources at
the biowulf cluster.
NR 48
TC 25
Z9 25
U1 1
U2 14
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 DEC 16
PY 2010
VL 114
IS 49
BP 16290
EP 16297
DI 10.1021/jp108731r
PG 8
WC Chemistry, Physical
SC Chemistry
GA 690GO
UT WOS:000284990700031
PM 21047091
ER
PT J
AU Antonellis, A
Dennis, MY
Burzynski, G
Huynh, J
Maduro, V
Hodonsky, CJ
Khajavi, M
Szigeti, K
Mukkamala, S
Bessling, SL
Pavan, WJ
McCallion, AS
Lupski, JR
Green, ED
AF Antonellis, Anthony
Dennis, Megan Y.
Burzynski, Grzegorz
Huynh, Jimmy
Maduro, Valerie
Hodonsky, Chani J.
Khajavi, Mehrdad
Szigeti, Kinga
Mukkamala, Sandeep
Bessling, Seneca L.
Pavan, William J.
McCallion, Andrew S.
Lupski, James R.
Green, Eric D.
CA NISC Comparative Sequencing Progra
TI A Rare Myelin Protein Zero (MPZ) Variant Alters Enhancer Activity In
Vitro and In Vivo
SO PLOS ONE
LA English
DT Article
ID GROWTH-RESPONSE 2; TRANSCRIPTION FACTOR SOX10; MARIE-TOOTH NEUROPATHY;
FUNCTIONAL CONSEQUENCES; PERIPHERAL-NERVE; SCHWANN-CELLS; GENE;
MUTATIONS; ZEBRAFISH; EGR2
AB Background: Myelin protein zero (MPZ) is a critical structural component of myelin in the peripheral nervous system. The MPZ gene is regulated, in part, by the transcription factors SOX10 and EGR2. Mutations in MPZ, SOX10, and EGR2 have been implicated in demyelinating peripheral neuropathies, suggesting that components of this transcriptional network are candidates for harboring disease-causing mutations (or otherwise functional variants) that affect MPZ expression.
Methodology: We utilized a combination of multi-species sequence comparisons, transcription factor-binding site predictions, targeted human DNA re-sequencing, and in vitro and in vivo enhancer assays to study human non-coding MPZ variants.
Principal Findings: Our efforts revealed a variant within the first intron of MPZ that resides within a previously described SOX10 binding site is associated with decreased enhancer activity, and alters binding of nuclear proteins. Additionally, the genomic segment harboring this variant directs tissue-relevant reporter gene expression in zebrafish.
Conclusions: This is the first reported MPZ variant within a cis-acting transcriptional regulatory element. While we were unable to implicate this variant in disease onset, our data suggests that similar non-coding sequences should be screened for mutations in patients with neurological disease. Furthermore, our multi-faceted approach for examining the functional significance of non-coding variants can be readily generalized to study other loci important for myelin structure and function.
C1 [Antonellis, Anthony; Hodonsky, Chani J.] Univ Michigan, Sch Med, Dept Human Genet, Ann Arbor, MI 48109 USA.
[Antonellis, Anthony] Univ Michigan, Sch Med, Dept Neurol, Ann Arbor, MI USA.
[Dennis, Megan Y.; Maduro, Valerie; Mukkamala, Sandeep; Green, Eric D.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
[Burzynski, Grzegorz; Huynh, Jimmy; Bessling, Seneca L.; McCallion, Andrew S.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA.
[Burzynski, Grzegorz; Huynh, Jimmy; Bessling, Seneca L.; McCallion, Andrew S.] Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Pathobiol, Baltimore, MD USA.
[Khajavi, Mehrdad; Szigeti, Kinga; Lupski, James R.] Dept Mol & Human Genet, Houston, TX USA.
[Szigeti, Kinga] Dept Neurol, Houston, TX USA.
[Green, Eric D.; NISC Comparative Sequencing Progra] NHGRI, NIH Intramural Sequencing Ctr NISC, NIH, Bethesda, MD 20892 USA.
[Pavan, William J.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
[Lupski, James R.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
[Lupski, James R.] Texas Childrens Hosp, Houston, TX 77030 USA.
RP Antonellis, A (reprint author), Univ Michigan, Sch Med, Dept Human Genet, Ann Arbor, MI 48109 USA.
EM egreen@nhgri.nih.gov
FU National Human Genome Research Institute (National Institutes of
Health); Charcot-Marie-Tooth Association; National Institute of General
Medical Sciences [R01GM071648]; National Institute of Neurological
Diseases and Stroke [R01NS062972, R00NS060983]
FX This work was supported in part by the Intramural Research Program of
the National Human Genome Research Institute (National Institutes of
Health), a fellowship (AA) and grant (JRL) from the Charcot-Marie-Tooth
Association, grant R01GM071648 from the National Institute of General
Medical Sciences (ASM), grant R01NS062972 (ASM) from the National
Institute of Neurological Diseases and Stroke, and grant R00NS060983
from the National Institute of Neurological Diseases and Stroke (AA).
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 43
TC 6
Z9 6
U1 0
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 DEC 16
PY 2010
VL 5
IS 12
AR e14346
DI 10.1371/journal.pone.0014346
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 695OI
UT WOS:000285381200004
PM 21179557
ER
PT J
AU Hessol, NA
Napolitano, LA
Smith, D
Lie, Y
Levine, A
Young, M
Cohen, M
Minkoff, H
Anastos, K
D'Souza, G
Greenblatt, RM
Goedert, JJ
AF Hessol, Nancy A.
Napolitano, Laura A.
Smith, Dawn
Lie, Yolanda
Levine, Alexandra
Young, Mary
Cohen, Mardge
Minkoff, Howard
Anastos, Kathryn
D'Souza, Gypsyamber
Greenblatt, Ruth M.
Goedert, James J.
TI HIV Tropism and Decreased Risk of Breast Cancer
SO PLOS ONE
LA English
DT Article
ID WOMENS INTERAGENCY HIV; IN-VITRO; CXCR4; CHEMOKINE; RECEPTOR; CELLS;
INFECTION; AIDS; INHIBITION; PATHWAY
AB Background: During the first two decades of the U. S. AIDS epidemic, and unlike some malignancies, breast cancer risk was significantly lower for women with human immunodeficiency virus (HIV) infection compared to the general population. This deficit in HIV-associated breast cancer could not be attributed to differences in survival, immune deficiency, childbearing or other breast cancer risk factors. HIV infects mononuclear immune cells by binding to the CD4 molecule and to CCR5 or CXCR4 chemokine coreceptors. Neoplastic breast cells commonly express CXCR4 but not CCR5. In vitro, binding HIV envelope protein to CXCR4 has been shown to induce apoptosis of neoplastic breast cells. Based on these observations, we hypothesized that breast cancer risk would be lower among women with CXCR4-tropic HIV infection.
Methods and Findings: We conducted a breast cancer nested case-control study among women who participated in the WIHS and HERS HIV cohort studies with longitudinally collected risk factor data and plasma. Cases were HIV-infected women (mean age 46 years) who had stored plasma collected within 24 months of breast cancer diagnosis and an HIV viral load >= 500 copies/mL. Three HIV-infected control women, without breast cancer, were matched to each case based on age and plasma collection date. CXCR4-tropism was determined by a phenotypic tropism assay. Odds ratios (OR) and 95% confidence intervals (CI) for breast cancer were estimated by exact conditional logistic regression. Two (9%) of 23 breast cancer cases had CXCR4-tropic HIV, compared to 19 (28%) of 69 matched controls. Breast cancer risk was significantly and independently reduced with CXCR4 tropism (adjusted odds ratio, 0.10, 95% CI 0.002-0.84) and with menopause (adjusted odds ratio, 0.08, 95% CI 0.001-0.83). Adjustment for CD4(+) cell count, HIV viral load, and use of antiretroviral therapy did not attenuate the association between infection with CXCR4-tropic HIV and breast cancer.
Conclusions: Low breast cancer risk with HIV is specifically linked to CXCR4-using variants of HIV. These variants are thought to exclusively bind to and signal through a receptor that is commonly expressed on hyperplastic and neoplastic breast duct cells. Additional studies are needed to confirm these observations and to understand how CXCR4 might reduce breast cancer risk.
C1 [Hessol, Nancy A.; Greenblatt, Ruth M.] Univ Calif San Francisco, Dept Clin Pharm, San Francisco, CA 94143 USA.
[Napolitano, Laura A.; Lie, Yolanda] Monogram Biosci, San Francisco, CA USA.
[Napolitano, Laura A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Smith, Dawn] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Levine, Alexandra] City Hope Natl Med Ctr, Duarte, CA 91010 USA.
[Young, Mary] Georgetown Univ, Sch Med, Washington, DC USA.
[Cohen, Mardge] Rush Univ, Dept Med, Chicago, IL 60612 USA.
[Cohen, Mardge] Rush Univ, Stroger Hosp, Chicago, IL 60612 USA.
[Minkoff, Howard] SUNY Hlth Sci Ctr, Brooklyn, NY 11203 USA.
[Minkoff, Howard] Maimonides Hosp, Brooklyn, NY 11219 USA.
[Anastos, Kathryn] Montefiore Med Ctr, Bronx, NY 10467 USA.
[D'Souza, Gypsyamber] Johns Hopkins Sch Publ Hlth, Baltimore, MD USA.
[Goedert, James J.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Levine, Alexandra] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
RP Hessol, NA (reprint author), Univ Calif San Francisco, Dept Clin Pharm, San Francisco, CA 94143 USA.
EM goedertj@mail.nih.gov
FU National Institutes of Health; Centers for Disease Control and
Prevention; National Institute of Allergy and Infectious Diseases
[UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993,
UO1-AI-42590]; Eunice Kennedy Shriver National Institute of Child Health
and Human Development [UO1-HD-32632]; National Cancer Institute;
National Institute on Drug Abuse; National Institute on Deafness and
Other Communication Disorders; National Center for Research Resources
(UCSF-CTSI) [UL1 RR024131]; Centers for Disease Control and Prevention
[U64/CCU106795, U64/CCU206798, U64/CCU306802, U64/CCU506831]
FX Funded in part by the Intramural Research Program of the National Cancer
Institute (JJG), by other components of the National Institutes of
Health, and by the Centers for Disease Control and Prevention. The WIHS
is funded by the National Institute of Allergy and Infectious Diseases
(UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993,
and UO1-AI-42590) and by the Eunice Kennedy Shriver National Institute
of Child Health and Human Development (UO1-HD-32632). The WIHS is
co-funded by the National Cancer Institute, the National Institute on
Drug Abuse, and the National Institute on Deafness and Other
Communication Disorders. Funding is also provided by the National Center
for Research Resources (UCSF-CTSI Grant Number UL1 RR024131). The HIV
Epidemiology Research Study (HERS) was funded through Centers for
Disease Control and Prevention cooperative agreements U64/CCU106795,
U64/CCU206798, U64/CCU306802, and U64/CCU506831. Monogram Biosciences
supported tropism testing and all assays were performed by the Monogram
Clinical Reference Laboratory. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 29
TC 13
Z9 13
U1 0
U2 5
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 DEC 16
PY 2010
VL 5
IS 12
AR e14349
DI 10.1371/journal.pone.0014349
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 695OI
UT WOS:000285381200006
PM 21179547
ER
PT J
AU Ledgerwood, JE
Costner, P
Desai, N
Holman, L
Enama, ME
Yamshchikov, G
Mulangu, S
Hu, Z
Andrews, CA
Sheets, RA
Koup, RA
Roederer, M
Bailer, R
Mascola, JR
Pau, MG
Sullivan, NJ
Goudsmit, J
Nabel, GJ
Graham, BS
AF Ledgerwood, J. E.
Costner, P.
Desai, N.
Holman, L.
Enama, M. E.
Yamshchikov, G.
Mulangu, S.
Hu, Z.
Andrews, C. A.
Sheets, R. A.
Koup, R. A.
Roederer, M.
Bailer, R.
Mascola, J. R.
Pau, M. G.
Sullivan, N. J.
Goudsmit, J.
Nabel, G. J.
Graham, B. S.
CA VRC 205 Study Team
TI A replication defective recombinant Ad5 vaccine expressing Ebola virus
GP is safe and immunogenic in healthy adults
SO VACCINE
LA English
DT Article
DE Adenovirus; Gene-based vaccines; Ebola; Filovirus vaccine
ID TYPE-1 GAG GENE; ADENOVIRUS VECTORS; NONHUMAN-PRIMATES; HIV-1 VACCINE;
OF-CONCEPT; CANDIDATE VACCINE; HEMORRHAGIC-FEVER; INDUCED IMMUNITY;
PHASE-1 SAFETY; RHESUS-MONKEYS
AB Ebola virus causes irregular outbreaks of severe hemorrhagic fever in equatorial Africa. Case mortality remains high; there is no effective treatment and outbreaks are sporadic and unpredictable. Studies of Ebola virus vaccine platforms in non-human primates have established that the induction of protective immunity is possible and safety and human immunogenicity has been demonstrated in a previous Phase I clinical trial of a 1st generation Ebola DNA vaccine. We now report the safety and immunogenicity of a recombinant adenovirus serotype 5 (rAd5) vaccine encoding the envelope glycoprotein (GP) from the Zaire and Sudan Ebola virus species, in a randomized, placebo-controlled, double-blinded, dose escalation, Phase I human study. Thirty-one healthy adults received vaccine at 2 x 10(9) (n = 12), or 2 x 10(10) (n = 11) viral particles or placebo (n = 8) as an intramuscular injection. Antibody responses were assessed by ELISA and neutralizing assays; and T cell responses were assessed by ELISpot and intracellular cytokine staining assays. This recombinant Ebola virus vaccine was safe and subjects developed antigen specific humoral and cellular immune responses. Published by Elsevier Ltd.
C1 [Ledgerwood, J. E.; Costner, P.; Desai, N.; Holman, L.; Enama, M. E.; Yamshchikov, G.; Mulangu, S.; Hu, Z.; Andrews, C. A.; Sheets, R. A.; Koup, R. A.; Roederer, M.; Bailer, R.; Mascola, J. R.; Sullivan, N. J.; Nabel, G. J.; Graham, B. S.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Pau, M. G.; Goudsmit, J.] Crucell Holland BV, Leiden, Netherlands.
RP Ledgerwood, JE (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike,Bldg 10,CRC,Room 5-2440,40 Co, Bethesda, MD 20892 USA.
EM Ledgerwood@mail.nih.gov
NR 47
TC 76
Z9 82
U1 1
U2 26
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
EI 1873-2518
J9 VACCINE
JI Vaccine
PD DEC 16
PY 2010
VL 29
IS 2
BP 304
EP 313
DI 10.1016/j.vaccine.2010.10.037
PG 10
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 717OM
UT WOS:000287057300019
PM 21034824
ER
PT J
AU Keyes, KM
Hatzenbuehler, ML
McLaughlin, KA
Link, B
Olfson, M
Grant, BF
Hasin, D
AF Keyes, K. M.
Hatzenbuehler, M. L.
McLaughlin, K. A.
Link, B.
Olfson, M.
Grant, B. F.
Hasin, D.
TI Stigma and Treatment for Alcohol Disorders in the United States
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE alcohol drinking; alcoholics anonymous; alcoholism; mental disorders;
psychiatric therapeutic processes; shame; therapeutics; United States
ID SUBSTANCE USE DISORDERS; NATIONAL EPIDEMIOLOGIC SURVEY; INTERVIEW
SCHEDULE AUDADIS; GENERAL-POPULATION SAMPLE; PSYCHIATRIC DIAGNOSTIC
MODULES; SERIOUS MENTAL-ILLNESS; DSM-IV ALCOHOL; SERVICE UTILIZATION;
PERCEIVED STIGMA; SOCIAL DISTANCE
AB Among a nationally representative sample of adults with an alcohol use disorder, the authors tested whether perceived stigmatization of alcoholism was associated with a lower likelihood of receiving alcohol-related services. Data were drawn from a face-to-face epidemiologic survey of 34,653 adults interviewed in 2004-2005 who were aged 20 years or older and residing in households and group quarters in the United States. Alcohol abuse/dependence was diagnosed by using the Alcohol Use Disorder and Associated Disabilities Interview Schedule-Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, version (AUDADIS-IV). The stigma measure used was the Perceived Devaluation-Discrimination Scale. The main outcome was lifetime intervention including professional services and 12-step groups for alcohol disorders. Individuals with a lifetime diagnosis of an alcohol use disorder were less likely to utilize alcohol services if they perceived higher stigma toward individuals with alcohol disorders (odds ratio = 0.37, 95% confidence interval: 0.18, 0.76). Higher perceived stigma was associated with male gender (beta = -0.75; P < 0.01), nonwhite compared with non-Hispanic white race/ethnicity, lower income (beta = 1.0; P < 0.01), education (beta = 1.48; P < 0.01), and being previously married (beta = 0.47; P = 0.02). Individuals reporting close contact with an alcohol-disordered individual (e.g., relative with an alcohol problem) reported lower perceived stigma (beta = -1.70; P < 0.01). A link between highly stigmatized views of alcoholism and lack of services suggests that stigma reduction should be integrated into public health efforts to promote alcohol treatment.
C1 [Keyes, K. M.] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY 10032 USA.
[Keyes, K. M.; Link, B.; Olfson, M.; Hasin, D.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
[Hatzenbuehler, M. L.] Yale Univ, Dept Psychol, New Haven, CT 06520 USA.
[McLaughlin, K. A.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Grant, B. F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH,Dept Hlth & Human Serv, Bethesda, MD USA.
[Hasin, D.] Columbia Univ, Dept Psychiat, Coll Phys & Surg, New York, NY USA.
RP Keyes, KM (reprint author), Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, 722 W 168th St, New York, NY 10032 USA.
EM kmk2104@columbia.edu
RI Link, Bruce/N-9087-2013;
OI Link, Bruce/0000-0001-9980-7450; McLaughlin, Katie/0000-0002-1362-2410
FU National Institute on Alcoholism and Alcohol Abuse [K05 AA014223];
National Institute on Drug Abuse [RO1 DA018652, R21 DA020667,
F31-DA026689]; New York State Psychiatric Institute
FX This research was supported in part by grants from the National
Institute on Alcoholism and Alcohol Abuse (K05 AA014223 to D. H.), the
National Institute on Drug Abuse (RO1 DA018652 to D. H.; R21 DA020667),
a fellowship from the National Institute of Drug Abuse (F31-DA026689 to
K. M. K.), and support from the New York State Psychiatric Institute.
NR 87
TC 83
Z9 84
U1 3
U2 30
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD DEC 15
PY 2010
VL 172
IS 12
BP 1364
EP 1372
DI 10.1093/aje/kwq304
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 692ZA
UT WOS:000285193200007
PM 21044992
ER
PT J
AU Martin, WJ
Brynes, S
Walsh, JW
AF Martin, William J., II
Brynes, Sue
Walsh, John W.
TI Chilean Miners and Biomedical Research A Modest Proposal
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Editorial Material
C1 [Martin, William J., II] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Acute Lung Injury & Repair, Bethesda, MD USA.
[Brynes, Sue] LAM Fdn, Cincinnati, OH USA.
[Walsh, John W.] Alpha One Fdn, Miami, FL USA.
RP Martin, WJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Acute Lung Injury & Repair, Bethesda, MD USA.
NR 2
TC 1
Z9 1
U1 0
U2 2
PU AMER THORACIC SOC
PI NEW YORK
PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA
SN 1073-449X
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD DEC 15
PY 2010
VL 182
IS 12
BP 1459
EP 1460
DI 10.1164/rccm.201010-1694ED
PG 2
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 697RU
UT WOS:000285534600001
PM 21159901
ER
PT J
AU Erzurum, S
Rounds, SI
Stevens, T
Aldred, M
Aliotta, J
Archer, SL
Asosingh, K
Balaban, R
Bauer, N
Bhattacharya, J
Bogaard, H
Choudhary, G
Dorn, GW
Dweik, R
Fagan, K
Fallon, M
Finkel, T
Geraci, M
Gladwin, MT
Hassoun, PM
Humbert, M
Kaminski, N
Kawut, SM
Loscalzo, J
McDonald, D
McMurtry, IF
Newman, J
Nicolls, M
Rabinovitch, M
Shizuru, J
Oka, M
Polgar, P
Rodman, D
Schumacker, P
Stenmark, K
Tuder, R
Voelkel, N
Sullivan, E
Weinshilboum, R
Yoder, MC
Zhao, YM
Gail, D
Moore, TM
AF Erzurum, Serpil
Rounds, Sharon I.
Stevens, Troy
Aldred, Micheala
Aliotta, Jason
Archer, Stephen L.
Asosingh, Kewal
Balaban, Robert
Bauer, Natalie
Bhattacharya, Jahar
Bogaard, Harm
Choudhary, Gaurav
Dorn, Gerald W., II
Dweik, Raed
Fagan, Karen
Fallon, Michael
Finkel, Toren
Geraci, Mark
Gladwin, Mark T.
Hassoun, Paul M.
Humbert, Marc
Kaminski, Naftali
Kawut, Steven M.
Loscalzo, Joseph
McDonald, Donald
McMurtry, Ivan F.
Newman, John
Nicolls, Mark
Rabinovitch, Marlene
Shizuru, Judy
Oka, Masahiko
Polgar, Peter
Rodman, David
Schumacker, Paul
Stenmark, Kurt
Tuder, Rubin
Voelkel, Norbert
Sullivan, Eugene
Weinshilboum, Richard
Yoder, Mervin C.
Zhao, Yingming
Gail, Dorothy
Moore, Timothy M.
TI Strategic Plan for Lung Vascular Research An NHLBI-ORDR Workshop Report
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
DE right ventricle; pulmonary hypertension; metabolism; genomics;
phenotyping
ID PULMONARY ARTERIAL-HYPERTENSION; HEREDITARY HEMORRHAGIC TELANGIECTASIA;
ENDOTHELIAL PROGENITOR CELLS; RIGHT-VENTRICULAR FUNCTION; GENE
MICROARRAY ANALYSIS; RIGHT-HEART-FAILURE; HEPATOPULMONARY SYNDROME;
MOLECULAR-MECHANISMS; DRUG-THERAPY; END-POINTS
AB The Division of Lung Diseases of the National Heart, Lung, and Blood Institute, with the Office of Rare Diseases Research, held a workshop to identify priority areas and strategic goals to enhance and accelerate research that will result in improved understanding of the lung vasculature, translational research needs, and ultimately the care of patients with pulmonary vascular diseases. Multidisciplinary experts with diverse experience in laboratory, translational, and clinical studies identified seven priority areas and discussed limitations in our current knowledge, technologies, and approaches. The focus for future research efforts include the following: (1) better characterizing vascular genotype phenotype relationships and incorporating systems biology approaches when appropriate; (2) advancing our understanding of pulmonary vascular metabolic regulatory signaling in health and disease; (3) expanding our knowledge of the biologic relationships between the lung circulation and circulating elements, systemic vascular function, and right heart function and disease; (4) improving translational research for identifying disease-modifying therapies for the pulmonary hypertensive diseases; (5) establishing an appropriate and effective platform for advancing translational findings into clinical studies testing; and (6) developing the specific technologies and tools that will be enabling for these goals, such as question-guided imaging techniques and lung vascular investigator training programs. Recommendations from this workshop will be used within the Lung Vascular Biology and Disease Extramural Research Program for planning and strategic implementation purposes.
C1 [Moore, Timothy M.] NHLBI, Div Lung Dis, NIH, Bethesda, MD 20892 USA.
[Erzurum, Serpil; Asosingh, Kewal; Dweik, Raed] Cleveland Clin, Dept Pathobiol, Cleveland, OH 44106 USA.
[Rounds, Sharon I.; Choudhary, Gaurav] Brown Univ, Dept Med, Providence Vet Affairs Med Ctr, Warren Alpert Med Sch, Providence, RI 02912 USA.
[Stevens, Troy; Bauer, Natalie; Fagan, Karen; McMurtry, Ivan F.; Oka, Masahiko] Univ S Alabama, Ctr Lung Biol, Mobile, AL 36688 USA.
[Aliotta, Jason] Brown Univ, Dept Med, Div Pulm Sleep & Crit Care Med, Warren Alpert Med Sch, Providence, RI 02912 USA.
[Archer, Stephen L.] Univ Chicago, Dept Med, Cardiol Sect, Chicago, IL 60637 USA.
[Balaban, Robert] NHLBI, Cardiac Energet Lab, Bethesda, MD 20892 USA.
[Bhattacharya, Jahar] Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA.
[Bhattacharya, Jahar] Columbia Univ Coll Phys & Surg, Dept Physiol & Cellular Biophys, New York, NY 10032 USA.
[Bogaard, Harm; Voelkel, Norbert] Virginia Commonwealth Univ, Dept Med, Div Pulm & Crit Care Med, Richmond, VA 23298 USA.
[Dorn, Gerald W., II] Washington Univ, Sch Med, Dept Internal Med, St Louis, MO 63110 USA.
[Dorn, Gerald W., II] Washington Univ, Sch Med, Ctr Pharmacogenom, St Louis, MO USA.
[Fallon, Michael] Univ Texas Hlth Sci Ctr Houston, Sch Med, Dept Med, Div Gastroenterol Hepatol & Nutr, Houston, TX USA.
[Finkel, Toren] NHLBI, Translat Med Branch, Bethesda, MD 20892 USA.
[Geraci, Mark; Tuder, Rubin] Univ Colorado, Dept Med, Denver, CO USA.
[Gladwin, Mark T.; Kaminski, Naftali] Univ Pittsburgh, Sch Med, Dept Med, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA USA.
[Gladwin, Mark T.; Kaminski, Naftali] Univ Pittsburgh, Sch Med, Vasc Med Inst, Pittsburgh, PA USA.
[Hassoun, Paul M.] Johns Hopkins Univ, Div Pulm & Crit Care Med, Dept Med, Baltimore, MD USA.
[Humbert, Marc] Univ Paris 11, Hop Antoine Beclere, Paris, France.
[Kawut, Steven M.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA.
[Loscalzo, Joseph] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA.
[McDonald, Donald] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA.
[Newman, John] Vanderbilt Univ Sch Med, Dept Allergy Pulm & Crit Med, Nashville, TN USA.
[Nicolls, Mark] Stanford Univ, Dept Med, Sch Med, Div Pulm & Crit Care, Stanford, CA 94305 USA.
[Rabinovitch, Marlene] Stanford Univ, Vera Moulton Wall Ctr Pulm Vasc Dis, Sch Med, Stanford, CA 94305 USA.
[Shizuru, Judy] Stanford Univ, Dept Med Blood & Marrow Transplantat, Sch Med, Stanford, CA 94305 USA.
[Polgar, Peter] Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA.
[Rodman, David] Novartis Inst Biomed Res, Cambridge, MA USA.
[Schumacker, Paul] Northwestern Univ, Dept Pediat, Chicago, IL 60611 USA.
[Stenmark, Kurt] Univ Colorado, Dept Pediat, Denver, CO 80202 USA.
[Sullivan, Eugene] United Therapeut, Silver Spring, MD USA.
[Weinshilboum, Richard] Mayo Clin, Mayo Med Sch, Dept Mol Pharmacol & Expt Therapeut & Med, Rochester, MN USA.
[Yoder, Mervin C.] Indiana Univ Sch Med, Dept Pediat, Indianapolis, IN USA.
[Zhao, Yingming] Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USA.
RP Moore, TM (reprint author), NHLBI, Div Lung Dis, NIH, 6701 Rockledge Dr,Rockledge Ctr 2,Room 10182, Bethesda, MD 20892 USA.
EM mooretm@mail.nih.gov
RI Archer, Stephen/C-3621-2013;
OI Polgar, Peter/0000-0002-9112-1101
FU Division of Lung Diseases, National Heart, Lung, and Blood Institute,
NIH, Office of Rare Diseases Research, Office of the Director, NIH
FX Supported by the Division of Lung Diseases, National Heart, Lung, and
Blood Institute, NIH, Office of Rare Diseases Research, Office of the
Director, NIH.
NR 74
TC 27
Z9 27
U1 0
U2 5
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1073-449X
EI 1535-4970
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD DEC 15
PY 2010
VL 182
IS 12
BP 1554
EP 1562
DI 10.1164/rccm.201006-0869WS
PG 9
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 697RU
UT WOS:000285534600016
PM 20833821
ER
PT J
AU Vangala, K
Yanney, M
Hsiao, CT
Wu, WW
Shen, RF
Zou, SG
Sygula, A
Zhang, DM
AF Vangala, Karthikeshwar
Yanney, Michael
Hsiao, Cheng-Te
Wu, Wells W.
Shen, Rong-Fong
Zou, Sige
Sygula, Andrzej
Zhang, Dongmao
TI Sensitive Carbohydrate Detection Using Surface Enhanced Raman Tagging
SO ANALYTICAL CHEMISTRY
LA English
DT Article
ID ASSISTED-LASER-DESORPTION/IONIZATION; MASS-SPECTROMETRY; SILVER
NANOPARTICLES; SCATTERING; PROTEIN; QUANTIFICATION; GOLD;
OLIGOSACCHARIDES; DERIVATIZATION; SPECTROSCOPY
AB Glycomic analysis is an increasingly important field in biological and biomedical research as glycosylation is one of the most important protein post-translational modifications. We have developed a new technique to detect carbohydrates using surface enhanced Raman spectroscopy (SERS) by designing and applying a Rhodamine B derivative as the SERS tag. Using a reductive amination reaction, the Rhodamine-based tag (RT) was successfully conjugated to three model carbohydrates (glucose, lactose, and glucuronic acid). SERS detection limits obtained with a 633 nm HeNe laser were similar to 1 nM in concentration for all the RT-carbohydrate conjugates and similar to 10 fmol in total sample consumption. The dynamic range of the SERS method is about 4 orders of magnitude, spanning from 1 nM to 5 mu M. Ratiometric SERS quantification using isotope-substituted SERS internal references allows comparative quantifications of carbohydrates labeled with RT and deuterium/hydrogen substituted RT tags, respectively. In addition to enhancing the SERS detection of the tagged carbohydrates, the Rhodamine tagging facilitates fluorescence and mass spectrometric detection of carbohydrates. Current fluorescence sensitivity of RT-carbohydrates is similar to 3 nM in concentration while the mass spectrometry (MS) sensitivity is about 1 fmol, achieved with a linear ion trap electrospray ionization (ESI)-MS instrument. Potential applications that take advantage of the high SERS, fluorescence, and MS sensitivity of this SERS tagging strategy are discussed for practical glycomic analysis where carbohydrates may be quantified with a fluorescence and SERS technique and then identified with ESI-MS techniques.
C1 [Vangala, Karthikeshwar; Yanney, Michael; Sygula, Andrzej; Zhang, Dongmao] Mississippi State Univ, Dept Chem, Mississippi State, MS 39762 USA.
[Hsiao, Cheng-Te; Zou, Sige] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA.
[Wu, Wells W.; Shen, Rong-Fong] NIA, Prote & Analyt Biochem Unit, NIH, Baltimore, MD 21224 USA.
RP Zhang, DM (reprint author), Mississippi State Univ, Dept Chem, Mississippi State, MS 39762 USA.
EM dz33@msstate.edu
FU Department of Chemistry at Mississippi State University; MSU; National
Institute on Aging
FX D.Z. thanks Dr. Ed Lewis for allowing the use of the fluorimeter for the
fluorescence measurement. This work was supported by start-up funding
from the Department of Chemistry at Mississippi State University and a
Research Initiation Proposal Award from MSU provided to D.Z. and in part
by the Intramural Research Program of the National Institute on Aging to
S.Z. and R.-F.S.
NR 48
TC 19
Z9 21
U1 7
U2 83
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0003-2700
J9 ANAL CHEM
JI Anal. Chem.
PD DEC 15
PY 2010
VL 82
IS 24
BP 10164
EP 10171
DI 10.1021/ac102284x
PG 8
WC Chemistry, Analytical
SC Chemistry
GA 693HS
UT WOS:000285215800029
PM 21082777
ER
PT J
AU Lee, KM
Lee, KW
Jung, SK
Lee, EJ
Heo, YS
Bode, AM
Lubet, RA
Lee, HJ
Dong, ZG
AF Lee, Kyung Mi
Lee, Ki Won
Jung, Sung Keun
Lee, Eun Jung
Heo, Yong-Seok
Bode, Ann M.
Lubet, Ronald A.
Lee, Hyong Joo
Dong, Zigang
TI Kaempferol inhibits UVB-induced COX-2 expression by suppressing Src
kinase activity
SO BIOCHEMICAL PHARMACOLOGY
LA English
DT Article
DE Flavonoid; Photo-carcinogenesis; Skin cancer
ID NONMELANOMA SKIN-CANCER; C-SRC; MAP KINASE; MOUSE SKIN; CARCINOGENESIS;
ACTIVATION; CYCLOOXYGENASE-2; FLAVONOIDS; RADIATION; CELLS
AB Ultraviolet (UV) radiation is the primary environmental risk factor in the development of nonmelanoma skin cancer, and UVB in particular promotes tumor growth through various signaling pathways. Kaempferol, a flavonoid with anti-inflammatory and anti-oxidative properties, has been studied as a chemopreventive agent; however, little is known regarding its effects on UVB-induced photo-carcinogenesis. Here, we examined the effect of kaempferol on UVB-induced skin inflammation. We found that kaempferol suppressed UVB-induced cyclooxygenase-2 (COX-2) protein expression in mouse skin epidermal JB6 P+ cells and attenuated the UVB-induced transcriptional activities of cox-2 and activator protein-1 (AP-1). Kaempferol attenuated the UVB-induced phosphorylation of several mitogen-activated protein kinases (MAPKs), including ERKs, p38, and JNKs, but had no effect on the phosphorylation of the upstream MAPK regulator Src. However, in vitro and ex vivo kinase assays demonstrated that kaempferol suppressed Src kinase activity. Furthermore, in vivo data from mouse skin support the idea that kaempferol suppresses UVB-induced COX-2 expression by blocking Src kinase activity. A pull-down assay revealed that kaempferol competes with ATP for direct binding to Src. Docking data suggest that kaempferol docks easily into the ATP-binding site of Src, which is located between the N and the C lobes of the kinase domain. Taken together, these results suggest that kaempferol is a potent chemopreventive agent against skin cancer through its inhibitory interaction with Src. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Lee, Kyung Mi; Jung, Sung Keun; Lee, Eun Jung; Lee, Hyong Joo] Seoul Natl Univ, Dept Agr Biotechnol, Seoul 151921, South Korea.
[Lee, Kyung Mi; Lee, Ki Won; Jung, Sung Keun; Bode, Ann M.; Dong, Zigang] Univ Minnesota, Hormel Inst, Austin, MN 55912 USA.
[Lee, Kyung Mi; Lee, Ki Won] Konkuk Univ, Biomol Informat Ctr, Dept Biosci & Biotechnol, Seoul 143701, South Korea.
[Heo, Yong-Seok] Konkuk Univ, Dept Chem, Seoul 143701, South Korea.
[Lubet, Ronald A.] NCI, Div Canc Prevent & Control, Rockville, MD 20852 USA.
RP Lee, HJ (reprint author), Seoul Natl Univ, Dept Agr Biotechnol, Seoul 151921, South Korea.
EM leehyjo@snu.ac.kr; zgdong@hi.umn.edu
RI Heo, Yong-Seok/D-8244-2011
FU World Class University, World Class Institute [R31-2008-00-10056-0];
Priority Research Centers Program [2009-0093824]; National Research
Foundation of Korea; National Cancer Institute [N01-CN-53301 WA#14]
FX This study was supported by the World Class University Program
(R31-2008-00-10056-0), World Class Institute Program; and Priority
Research Centers Program (2009-0093824), the National Research
Foundation of Korea and National Cancer Institute (N01-CN-53301 WA#14).
NR 44
TC 45
Z9 49
U1 1
U2 4
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0006-2952
J9 BIOCHEM PHARMACOL
JI Biochem. Pharmacol.
PD DEC 15
PY 2010
VL 80
IS 12
SI SI
BP 2042
EP 2049
DI 10.1016/j.bcp.2010.06.042
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 679RB
UT WOS:000284177400028
PM 20599768
ER
PT J
AU Liu, B
Liu, L
Tsykin, A
Goodall, GJ
Green, JE
Zhu, M
Kim, CH
Li, JY
AF Liu, Bing
Liu, Lin
Tsykin, Anna
Goodall, Gregory J.
Green, Jeffrey E.
Zhu, Min
Kim, Chang Hee
Li, Jiuyong
TI Identifying functional miRNA-mRNA regulatory modules with correspondence
latent dirichlet allocation
SO BIOINFORMATICS
LA English
DT Article
ID HUMAN BREAST-CANCER; MICRORNA TARGETS; IDENTIFICATION; PREDICTION;
DISCOVERY; PATTERNS; SUBTYPES; GENES
AB Motivation: MicroRNAs ( miRNAs) are small non-coding RNAs that cause mRNA degradation and translational inhibition. They are important regulators of development and cellular homeostasis through their control of diverse processes. Recently, great efforts have been made to elucidate their regulatory mechanism, but the functions of most miRNAs and their precise regulatory mechanisms remain elusive. With more and more matched expression profiles of miRNAs and mRNAs having been made available, it is of great interest to utilize both expression profiles to discover the functional regulatory networks of miRNAs and their target mRNAs for potential biological processes that they may participate in.
Results: We present a probabilistic graphical model to discover functional miRNA regulatory modules at potential biological levels by integrating heterogeneous datasets, including expression profiles of miRNAs and mRNAs, with or without the prior target binding information. We applied this model to a mouse mammary dataset. It effectively captured several biological process specific modules involving miRNAs and their target mRNAs. Furthermore, without using prior target binding information, the identified miRNAs and mRNAs in each module show a large proportion of overlap with predicted miRNA target relationships, suggesting that expression profiles are crucial for both target identification and discovery of regulatory modules.
C1 [Liu, Bing; Liu, Lin; Li, Jiuyong] Univ S Australia, Sch Comp & Informat Sci, Mawson Lakes, SA 5095, Australia.
[Liu, Bing; Tsykin, Anna; Goodall, Gregory J.] SA Pathol, Ctr Canc Biol, Adelaide, SA 5000, Australia.
[Tsykin, Anna] Univ Adelaide, Sch Mol & Biomed Sci, Adelaide, SA 5005, Australia.
[Goodall, Gregory J.] Univ Adelaide, Dept Med, Adelaide, SA 5005, Australia.
[Green, Jeffrey E.; Zhu, Min] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA.
[Kim, Chang Hee] NCI, Lab Mol Technol, FCRDC, Frederick, MD 21702 USA.
RP Li, JY (reprint author), Univ S Australia, Sch Comp & Informat Sci, Mawson Lakes, SA 5095, Australia.
RI Liu, Bing/E-5854-2013; Li, Jiuyong/A-8134-2008;
OI Li, Jiuyong/0000-0002-9023-1878; Tsykin, Anna/0000-0001-5965-6803
FU Center for Cancer Research, NIH, Bethesda, MD, USA
FX Funding: Intramural Program, Center for Cancer Research, NIH, Bethesda,
MD, USA (in part).
NR 36
TC 49
Z9 51
U1 1
U2 18
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
J9 BIOINFORMATICS
JI Bioinformatics
PD DEC 15
PY 2010
VL 26
IS 24
BP 3105
EP 3111
DI 10.1093/bioinformatics/btq576
PG 7
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology; Statistics & Probability
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Computer Science; Mathematical & Computational Biology; Mathematics
GA 689RY
UT WOS:000284947700014
PM 20956247
ER
PT J
AU Abazyan, B
Nomura, J
Kannan, G
Ishizuka, K
Tamashiro, KL
Nucifora, F
Pogorelov, V
Ladenheim, B
Yang, CX
Krasnova, IN
Cadet, JL
Pardo, C
Mori, S
Kamiya, A
Vogel, MW
Sawa, A
Ross, CA
Pletnikov, MV
AF Abazyan, Bagrat
Nomura, Jun
Kannan, Geetha
Ishizuka, Koko
Tamashiro, Kellie L.
Nucifora, Frederick
Pogorelov, Vladimir
Ladenheim, Bruce
Yang, Chunxia
Krasnova, Irina N.
Cadet, Jean Lud
Pardo, Carlos
Mori, Susumu
Kamiya, Atsushi
Vogel, Michael W.
Sawa, Akira
Ross, Christopher A.
Pletnikov, Mikhail V.
TI Prenatal Interaction of Mutant DISC1 and Immune Activation Produces
Adult Psychopathology
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE DISC1; gene-environment interactions; mood disorders; mouse models;
schizophrenia; Tet-off system
ID DENDRITIC SPINE DENSITY; GENE-ENVIRONMENT INTERACTIONS; BIPOLAR
DISORDER; MOOD DISORDERS; BEHAVIORAL PHENOTYPES; INDUCIBLE EXPRESSION;
SCHIZOPHRENIA RISK; PREFRONTAL CORTEX; GENOMIC STRUCTURE; INFECTION
AB Background: Gene-environment interactions (GEI) are involved in the pathogenesis of mental diseases. We evaluated interaction between mutant human disrupted-in-schizophrenia 1 (mhDISC1) and maternal immune activation implicated in schizophrenia and mood disorders.
Methods: Pregnant mice were treated with saline or polyinosinic: polycytidylic acid at gestation day 9. Levels of inflammatory cytokines were measured in fetal and adult brains; expression of mhDISC1, endogenous DISC1, lissencephaly type 1, nuclear distribution protein nudE-like 1, glycoprotein 130, growth factor receptor-bound protein 2, and glycogen synthase kinase-3beta were assessed in cortical samples of newborn mice. Tissue content of monoamines, volumetric brain abnormalities, dendritic spine density in the hippocampus, and various domains of the mouse behavior repertoire were evaluated in adult male mice.
Results: Prenatal interaction produced anxiety, depression-like responses, and altered social behavior that were accompanied by decreased reactivity of the hypothalamic-pituitary-adrenal axis, attenuated serotonin neurotransmission in the hippocampus, reduced enlargement of lateral ventricles, decreased volumes of amygdala and periaqueductal gray matter and density of spines on dendrites of granule cells of the hippocampus. Prenatal interaction modulated secretion of inflammatory cytokines in fetal brains, levels of mhDISC1, endogenous mouse DISC1, and glycogen synthase kinase-3beta. The behavioral effects of GEI were observed only if mhDISC1 was expressed throughout the life span.
Conclusions: Prenatal immune activation interacted with mhDISC1 to produce the neurobehavioral phenotypes that were not seen in untreated mhDISC1 mice and that resemble aspects of major mental illnesses. Our DISC1 mouse model is a valuable system to study GEI relevant to mental illnesses.
C1 [Abazyan, Bagrat; Nomura, Jun; Kannan, Geetha; Nucifora, Frederick; Pogorelov, Vladimir; Yang, Chunxia; Ross, Christopher A.; Pletnikov, Mikhail V.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Div Neurobiol, Baltimore, MD 21287 USA.
[Pardo, Carlos; Mori, Susumu; Ross, Christopher A.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21287 USA.
[Sawa, Akira; Ross, Christopher A.; Pletnikov, Mikhail V.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21287 USA.
[Mori, Susumu] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21287 USA.
[Ross, Christopher A.] Johns Hopkins Univ, Sch Med, Dept Pharmacol, Baltimore, MD 21287 USA.
[Pletnikov, Mikhail V.] Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Pathobiol, Baltimore, MD 21287 USA.
[Kannan, Geetha; Sawa, Akira; Ross, Christopher A.; Pletnikov, Mikhail V.] Johns Hopkins Univ, Sch Med, Program Cellular & Mol Med, Baltimore, MD 21287 USA.
[Ishizuka, Koko; Kamiya, Atsushi; Sawa, Akira] Johns Hopkins Univ, Sch Med, Program Mol Psychiat, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA.
[Sawa, Akira] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21287 USA.
[Ladenheim, Bruce; Krasnova, Irina N.; Cadet, Jean Lud] Natl Inst Drug Abuse, Mol Neuropsychiat Branch, NIH, US Dept HHS, Baltimore, MD USA.
[Vogel, Michael W.] Univ Maryland, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA.
RP Pletnikov, MV (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Div Neurobiol, 600 N Wolfe St,CMSC 8-121, Baltimore, MD 21287 USA.
EM mpletnik@jhmi.edu
RI Nomura, Jun/C-2411-2011; Ross, Christopher/H-8395-2013; kamiya,
atsushi/L-8550-2016;
OI Vogel, Michael/0000-0002-8402-1495; Nomura, Jun/0000-0003-0817-2643
FU National Institute of Mental Health; Autism Speaks; National Alliance
for Research on Schizophrenia and Depression; Mortimer W. Sackler
Foundation; Cell Science Research Foundation Japan; National Institutes
of Health/National Institute on Drug Abuse
FX The study was supported by National Institute of Mental Health, Autism
Speaks, National Alliance for Research on Schizophrenia and Depression,
and the Mortimer W. Sackler Foundation (MVP); The Cell Science Research
Foundation Japan (JN); and by National Institutes of Health/National
Institute on Drug Abuse-Intramural Research Program (BL, INK, JLC).
NR 82
TC 111
Z9 114
U1 3
U2 9
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 DEC 15
PY 2010
VL 68
IS 12
BP 1172
EP 1181
DI 10.1016/j.biopsych.2010.09.022
PG 10
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 695QZ
UT WOS:000285389000015
PM 21130225
ER
PT J
AU Metaferia, BB
Rittler, M
Gheeya, JS
Lee, A
Hempel, H
Plaza, A
Stetler-Stevenson, WG
Bewley, CA
Khan, J
AF Metaferia, Belhu B.
Rittler, Matthew
Gheeya, Jinesh S.
Lee, Albert
Hempel, Heidi
Plaza, Alberto
Stetler-Stevenson, William G.
Bewley, Carole A.
Khan, Javed
TI Synthesis of novel cyclic NGR/RGD peptide analogs via on resin click
chemistry
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Click chemistry; Aminopeptidase N; Cyclic peptides; Targeted delivery;
Fluorescence polarization
ID TUMOR VASCULATURE; AMINOPEPTIDASE N; PHAGE DISPLAY; CYCLOADDITION;
THERAPEUTICS; ANGIOGENESIS; CYCLIZATION; INTEGRINS; DELIVERY; LIGANDS
AB Targeted drug deliveries as well as high resolution imaging of cancerous tissues and organs via specific cancer cell markers have become important in chemotherapeutic interventions of cancer treatment. Short peptides such as RGD and NGR are showing promising results for targeted drug delivery and in vivo imaging. We have applied on resin Huisgen's 1,3-dipolar cycloaddition to synthesize new cyclic RGD and NGR peptide analogs. Preliminary binding assays of these new analogs by fluorescence polarization indicates specific binding to purified CD13 (Aminopeptidase N) and cell lysates from MCF-7 and SKOV-3 cancer cell lines. Published by Elsevier Ltd.
C1 [Metaferia, Belhu B.; Gheeya, Jinesh S.; Lee, Albert; Hempel, Heidi; Khan, Javed] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Rittler, Matthew; Stetler-Stevenson, William G.] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Plaza, Alberto; Bewley, Carole A.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Khan, J (reprint author), NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
EM khanjav@mail.nih.gov
RI Stetler-Stevenson, William/H-6956-2012; Khan, Javed/P-9157-2014;
OI Stetler-Stevenson, William/0000-0002-5500-5808; Khan,
Javed/0000-0002-5858-0488; Gheeya, Jinesh/0000-0002-5246-6262
FU Center for Cancer Research, National Cancer Institute; National
Institute of Diabetes and Digestive and Kidney Diseases
FX We thank Dr. John Lloyd and Mr. Noel Whittaker from NIDDK/LBC for their
assistance with mass spectrometry analysis. We thank Ms. Jessica L.
Keffer for her assistance in the NMR experiments and analysis. This work
was supported by Intramural Research Programs, Center for Cancer
Research, National Cancer Institute (J.K.) and National Institute of
Diabetes and Digestive and Kidney Diseases (C.A.B.).
NR 23
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U1 1
U2 28
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD DEC 15
PY 2010
VL 20
IS 24
BP 7337
EP 7340
DI 10.1016/j.bmcl.2010.10.064
PG 4
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 681QW
UT WOS:000284332900032
PM 21050757
ER
PT J
AU Figg, WD
Figg, WD
AF Figg, William D., II
Figg, William D., Sr.
TI Cabazitaxel Filling one of the gaps in the treatment of prostate cancer
SO CANCER BIOLOGY & THERAPY
LA English
DT Editorial Material
DE taxane; chemotherapy; metastatic cancer; prostate cancer; cabazitaxel;
castrate resistant; survival; FDA approval
ID MITOXANTRONE PLUS PREDNISONE; PHASE-II TRIAL; EVERY 3 WEEKS; DOCETAXEL;
CHEMOTHERAPY; THALIDOMIDE; TAXANE
C1 [Figg, William D., II; Figg, William D., Sr.] NCI, NIH, Bethesda, MD 20892 USA.
RP Figg, WD (reprint author), NCI, NIH, Bethesda, MD 20892 USA.
EM wdfigg@helix.nih.gov; wdfigg@helix.nih.gov
RI Figg Sr, William/M-2411-2016
NR 15
TC 4
Z9 5
U1 0
U2 2
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4047
J9 CANCER BIOL THER
JI Cancer Biol. Ther.
PD DEC 15
PY 2010
VL 10
IS 12
BP 1233
EP 1234
DI 10.4161/cbt.10.12.14085
PG 2
WC Oncology
SC Oncology
GA 695QT
UT WOS:000285388400004
PM 21107022
ER
PT J
AU Matsumoto, S
Yasui, H
Mitchell, JB
Krishna, MC
AF Matsumoto, Shingo
Yasui, Hironobu
Mitchell, James B.
Krishna, Murali C.
TI Imaging Cycling Tumor Hypoxia
SO CANCER RESEARCH
LA English
DT Review
ID INTERMITTENT HYPOXIA; TRANSIENT HYPOXIA; FREE-RADICALS; OXYGENATION;
CANCER; CELLS; HIF-1; RADIOSENSITIVITY; REOXYGENATION; ANGIOGENESIS
AB Cycling hypoxia is now a well-recognized phenomenon in animal and human solid tumors. Cycling hypoxia can exist more than 100-mu m distances from a microvessel, and some of these regions have been shown to exist adjacent to normal tissue. Fluctuations in pO(2) of approximately 20 mm Hg can occur with periodicities of minutes to hours and even days. These fluctuations have been attributed to changes in erythrocyte flux, perfusion, and also development of newer vascular networks. Cycling hypoxia has been shown to induce the expression of hypoxia-inducible transcription factor-1 alpha (HIF-1 alpha) and also confer tumor cells and tumor vascular endothelial cells with enhanced prosurvival pathways, making tumors less responsive to radiation and chemotherapy. Imaging of cycling hypoxia in tumors can provide capabilities to help plan appropriate treatment, by taking into account the magnitude and frequency of fluctuations and also their locations adjacent to normal tissue. Electron paramagnetic resonance imaging (EPRI) provides the ability to distinguish chronic and cycling hypoxic regions and has the required spatial and temporal resolutions to provide quantitative maps of tumor pO(2). EPRI can serve as a valuable tool in examining tumor pO(2) longitudinally in response to treatment and in an experimentally chosen time window to spatially map fluctuations in pO(2) noninvasively in animal models of implanted or orthotopic tumors, with a potential for human applications. Cancer Res; 70(24); 10019-23. (C) 2010 AACR.
C1 [Krishna, Murali C.] NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Krishna, MC (reprint author), NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bldg 10,Room B3B69,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM murali@helix.nih.gov
RI Yasui, Hironobu/E-3794-2010
FU Intramural NIH HHS [Z01 BC010476-05]
NR 27
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U1 1
U2 15
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2010
VL 70
IS 24
BP 10019
EP 10023
DI 10.1158/0008-5472.CAN-10-2821
PG 5
WC Oncology
SC Oncology
GA 694XD
UT WOS:000285334200001
PM 21159626
ER
PT J
AU Aloia, AL
Sfanos, KS
Isaacs, WB
Zheng, QZ
Maldarelli, F
De Marzo, AM
Rein, A
AF Aloia, Amanda L.
Sfanos, Karen S.
Isaacs, William B.
Zheng, Qizhi
Maldarelli, Frank
De Marzo, Angelo M.
Rein, Alan
TI XMRV: A New Virus in Prostate Cancer?
SO CANCER RESEARCH
LA English
DT Article
ID CHRONIC-FATIGUE-SYNDROME; SIMIAN IMMUNODEFICIENCY VIRUS; HUMAN
RETROVIRUS XMRV; INFECTIOUS RETROVIRUS; GENE-THERAPY; SEQUENCES;
MULTIPLE; DISEASE; TUMORS; BLOOD
AB Several recent articles have reported the presence of a gammaretrovirus, termed "XMRV" (xenotropic murine leukemia virus-related virus) in prostate cancers (PCa). If confirmed, this could have enormous implications for the detection, prevention, and treatment of PCa. However, other articles report failure to detect XMRV in PCa. We tested nearly 800 PCa samples, using a combination of real-time PCR and immunohistochemistry (IHC). The PCR reactions were simultaneously monitored for amplification of a single-copy human gene, to confirm the quality of the sample DNA and its suitability for PCR. Controls showed that the PCR assay could detect the XMRV in a single infected cell, even in the presence of a 10,000-fold excess of uninfected human cells. The IHC used 2 rabbit polyclonal antisera, each prepared against a purified murine leukemia virus (MLV) protein. Both antisera always stained XMRV-infected or -transfected cells, but never stained control cells. No evidence for XMRV in PCa was obtained in these experiments. We discuss possible explanations for the discrepancies in the results from different laboratories. It is possible that XMRV is not actually circulating in the human population; even if it is, the data do not seem to support a causal role for this virus in PCa. Cancer Res; 70(24); 10028-33. (C) 2010 AACR.
C1 [Aloia, Amanda L.; Maldarelli, Frank; Rein, Alan] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA.
[Sfanos, Karen S.; Zheng, Qizhi; De Marzo, Angelo M.] Brady Urol Res Inst, Dept Pathol, Baltimore, MD USA.
[Isaacs, William B.; De Marzo, Angelo M.] Brady Urol Res Inst, Dept Urol, Baltimore, MD USA.
[Isaacs, William B.; De Marzo, Angelo M.] Brady Urol Res Inst, Dept Oncol, Baltimore, MD USA.
[Isaacs, William B.; Zheng, Qizhi; De Marzo, Angelo M.] Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
RP Rein, A (reprint author), NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA.
EM ademarz@jhmi.edu; reina@mail.nih.gov
FU NCI-SPORE [P50CA58236]; Prevent Cancer Foundation; NIH, National Cancer
Institute, Center for Cancer Research
FX IHC studies and a number of the frozen prostate tissues for PCR assays
were supported by NCI-SPORE in prostate PCa P50CA58236. K.S. Sfanos is
supported by a postdoctoral fellowship award from the Prevent Cancer
Foundation. This research was supported in part by the Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research.
NR 24
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U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2010
VL 70
IS 24
BP 10028
EP 10033
DI 10.1158/0008-5472.CAN-10-2837
PG 6
WC Oncology
SC Oncology
GA 694XD
UT WOS:000285334200003
PM 20966126
ER
PT J
AU Roessler, S
Jia, HL
Budhu, A
Forgues, M
Ye, QH
Lee, JS
Thorgeirsson, SS
Sun, ZT
Tang, ZY
Qin, LX
Wang, XW
AF Roessler, Stephanie
Jia, Hu-Liang
Budhu, Anuradha
Forgues, Marshonna
Ye, Qing-Hai
Lee, Ju-Seog
Thorgeirsson, Snorri S.
Sun, Zhongtang
Tang, Zhao-You
Qin, Lun-Xiu
Wang, Xin Wei
TI A Unique Metastasis Gene Signature Enables Prediction of Tumor Relapse
in Early-Stage Hepatocellular Carcinoma Patients
SO CANCER RESEARCH
LA English
DT Article
ID BREAST-CANCER; INTRAHEPATIC RECURRENCE; PROSTATE-CANCER; RISK-FACTORS;
EXPRESSION; RESECTION; SURVIVAL; CLASSIFICATION; MANAGEMENT; PROGNOSIS
AB Metastasis-related recurrence often occurs in hepatocellular carcinoma (HCC) patients who receive curative therapies. At present, it is challenging to identify patients with high risk of recurrence, which would warrant additional therapies. In this study, we sought to analyze a recently developed metastasis-related gene signature for its utility in predicting HCC survival, using 2 independent cohorts consisting of a total of 386 patients who received radical resection. Cohort 1 contained 247 predominantly HBV-positive cases analyzed with an Affymetrix platform, whereas cohort 2 contained 139 cases with mixed etiology analyzed with the NCI Oligo Set microarray platform. We employed a survival risk prediction algorithm with training, test, and independent cross-validation strategies and found that the gene signature is predictive of overall and disease-free survival. Importantly, risk was significantly predicted independently of clinical characteristics and microarray platform. In addition, survival prediction was successful in patients with early disease, such as small (<5cm in diameter) and solitary tumors, and the signature predicted particularly well for early recurrence risk (<2 years), especially when combined with serum alpha fetoprotein or tumor staging. In conclusion, we have shown in 2 independent cohorts with mixed etiologies and ethnicity that the metastasis gene signature is a useful tool to predict HCC outcome, suggesting the general utility of this classifier. We recommend the use of this classifier as a molecular diagnostic test to assess the risk that an HCC patient will develop tumor relapse within 2 years after surgical resection, particularly for those with early-stage tumors and solitary presentation. Cancer Res; 70(24); 10202-12. (C) 2010 AACR.
C1 [Roessler, Stephanie; Budhu, Anuradha; Forgues, Marshonna; Wang, Xin Wei] NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA.
[Jia, Hu-Liang; Ye, Qing-Hai; Tang, Zhao-You; Qin, Lun-Xiu] Fudan Univ, Liver Canc Inst, Shanghai 200032, Peoples R China.
[Jia, Hu-Liang; Ye, Qing-Hai; Tang, Zhao-You; Qin, Lun-Xiu] Fudan Univ, Zhongshan Hosp, Shanghai 200032, Peoples R China.
[Lee, Ju-Seog; Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA.
[Sun, Zhongtang] Chinese Acad Med Sci, Inst Canc, Natl Lab Mol Oncol, Beijing 100021, Peoples R China.
RP Wang, XW (reprint author), NCI, Human Carcinogenesis Lab, NIH, 37 Convent Dr,Bldg 37,Room 3044A, Bethesda, MD 20892 USA.
EM qin.lunxiu@zs-hospital.sh.cn; xw3u@nih.gov
RI Wang, Xin/B-6162-2009
FU Center for Cancer Research; China National Key Projects for Infectious
Disease [2008ZX10002-021]; State Key Basic Research Program of China
[2009CB521701]; U.S. National Cancer Institute [Z01-BC 010313, Z01-BC
010876]
FX This work was supported by the intramural Research Program of the Center
for Cancer Research, the U.S. National Cancer Institute (Z01-BC 010313
and Z01-BC 010876), and by China National Key Projects for Infectious
Disease (2008ZX10002-021) and the State Key Basic Research Program of
China (2009CB521701).
NR 44
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U1 2
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2010
VL 70
IS 24
BP 10202
EP 10212
DI 10.1158/0008-5472.CAN-10-2607
PG 11
WC Oncology
SC Oncology
GA 694XD
UT WOS:000285334200022
PM 21159642
ER
PT J
AU Liu, M
Sakamaki, T
Casimiro, MC
Willmarth, NE
Quong, AA
Ju, XM
Ojeifo, J
Jiao, XM
Yeow, WS
Katiyar, S
Shirley, LA
Joyce, D
Lisanti, MP
Albanese, C
Pestell, RG
AF Liu, Manran
Sakamaki, Toshiyuki
Casimiro, Mathew C.
Willmarth, Nicole E.
Quong, Andrew A.
Ju, Xiaoming
Ojeifo, John
Jiao, Xuanmao
Yeow, Wen-Shuz
Katiyar, Sanjay
Shirley, L. Andrew
Joyce, David
Lisanti, Michael P.
Albanese, Christopher
Pestell, Richard G.
TI The Canonical NF-kappa B Pathway Governs Mammary Tumorigenesis in
Transgenic Mice and Tumor Stem Cell Expansion
SO CANCER RESEARCH
LA English
DT Article
ID BREAST-CANCER CELLS; CYCLIN D1; IKK-ALPHA; INDUCIBLE EXPRESSION;
SIGNALING PATHWAY; INITIATING CELLS; IN-VIVO; MACROPHAGES; GROWTH; GLAND
AB The role of mammary epithelial cell (MEC) NF-kappa B in tumor progression in vivo is unknown, as murine NF-kappa B components and kinases either are required for murine survival or interfere with normal mammary gland development. As NF-kappa B inhibitors block both tumor-associated macrophages (TAM) and MEC NF-kappa B, the importance of MEC NF-kappa B to tumor progression in vivo remained to be determined. Herein, an MEC-targeted inducible transgenic inhibitor of NF-kappa B (I kappa B alpha SR) was developed in ErbB2 mammary oncomice. Inducible suppression of NF-kappa B in the adult mammary epithelium delayed the onset and number of new tumors. Within similar sized breast tumors, TAM and tumor neoangiogenesis was reduced. Coculture experiments demonstrated MEC NF-kappa B enhanced TAM recruitment. Genome-wide expression and proteomic analysis showed that IkBaSR inhibited tumor stem cell pathways. IkBaSR inhibited breast tumor stem cell markers in transgenic tumors, reduced stem cell expansion in vitro, and repressed expression of Nanog and Sox2 in vivo and in vitro. MEC NF-kappa B contributes to mammary tumorigenesis. As we show that NF-kappa B contributes to expansion of breast tumor stem cells and heterotypic signals that enhance TAM and vasculogenesis, these processes may contribute to NF-kappa B-dependent mammary tumorigenesis. Cancer Res; 70(24); 10464-73. (C)2010 AACR.
C1 [Liu, Manran; Casimiro, Mathew C.; Willmarth, Nicole E.; Quong, Andrew A.; Ju, Xiaoming; Jiao, Xuanmao; Yeow, Wen-Shuz; Katiyar, Sanjay; Lisanti, Michael P.; Pestell, Richard G.] Thomas Jefferson Univ, Kimmel Canc Ctr, Dept Canc Biol, Philadelphia, PA 19107 USA.
[Shirley, L. Andrew] Thomas Jefferson Univ, Kimmel Canc Ctr, Dept Surg, Philadelphia, PA 19107 USA.
[Liu, Manran] Chongqing Med Univ, Minist Educ, Key Lab Clin Lab Diagnost, Chongqing, Peoples R China.
[Sakamaki, Toshiyuki] Niigata Univ Pharm & Appl Life Sci, Niigata, Japan.
[Ojeifo, John] NCI, Ctr Reduce Canc Hlth Disparities, Rockville, MD USA.
[Joyce, David] Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia.
[Albanese, Christopher] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA.
RP Pestell, RG (reprint author), Thomas Jefferson Univ, Kimmel Canc Ctr, Dept Canc Biol, 233 S 10th St, Philadelphia, PA 19107 USA.
EM Richard.Pestell@jefferson.edu
RI Lisanti, Michael/C-6866-2013
FU NIH [P30CA56036]; Dr. Ralph and Marian C. Falk Medical Research Trust;
Pennsylvania Department of Health; [R01CA70896]; [R01CA75503];
[R01CA107382]; [R01CA86072]; [R01CA120876]
FX This work was supported in part by R01CA70896, R01CA75503, R01CA107382,
R01CA86072 (R.G.P.), and R01CA120876 (M.P.L). The Kimmel Cancer Center
was supported by the NIH Cancer Center Core grant P30CA56036 (R.G.P.).
This project is funded in part from the Dr. Ralph and Marian C. Falk
Medical Research Trust and a grant from Pennsylvania Department of
Health (R.G.P.).
NR 42
TC 83
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U1 1
U2 6
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2010
VL 70
IS 24
BP 10464
EP 10473
DI 10.1158/0008-5472.CAN-10-0732
PG 10
WC Oncology
SC Oncology
GA 694XD
UT WOS:000285334200047
PM 21159656
ER
PT J
AU Bao, Y
Chen, JQ
Wu, Y
Leng, XH
Wang, E
Marincola, F
Radvanyi, LG
AF Bao, Y.
Chen, J. Q.
Wu, Y.
Leng, X-H
Wang, E.
Marincola, F.
Radvanyi, L. G.
TI TRPS-1, a New GATA Family Transcription Factor, Regulates
Epithelial-Mesenchymal Transition and Maintains an Estrogen Responsive,
Claudin-Positive Phenotype in Breast Cancer Cells
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2010
VL 70
SU 24
MA P6-08-14
DI 10.1158/0008-5472.SABCS10-P6-08-14
PG 1
WC Oncology
SC Oncology
GA V43QL
UT WOS:000209695800264
ER
PT J
AU Bode, AM
Li, J
Cho, YY
Ericson, ME
Lubet, RA
Grubbs, C
AF Bode, A. M.
Li, J.
Cho, Y. Y.
Ericson, M. E.
Lubet, R. A.
Grubbs, C.
TI Tumors Resistant to Iressa Treatment Show Increased Aberrant Expression
of CREB (Ser133)
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 Univ Minnesota, Austin, MN USA.
Univ Minnesota, Minneapolis, MN USA.
NCI, Rockville, MD USA.
Univ Alabama Birmingham, Birmingham, AL USA.
RI ericson, marna/C-9591-2017
OI ericson, marna/0000-0003-1862-4957
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2010
VL 70
SU 24
MA P2-07-03
DI 10.1158/0008-5472.SABCS10-P2-07-03
PG 1
WC Oncology
SC Oncology
GA V43QL
UT WOS:000209695801071
ER
PT J
AU Eng-Wong, J
Venzon, D
Cohen, P
Isaacs, C
Warren, R
Wedam, S
Zujewski, JA
Korde, L
Byrne, C
AF Eng-Wong, J.
Venzon, D.
Cohen, P.
Isaacs, C.
Warren, R.
Wedam, S.
Zujewski, J. A.
Korde, L.
Byrne, C.
TI Effect of Exemestane on Mammographic Density in Postmenopausal Women at
Risk for Breast Cancer
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 Georgetown Univ, Washington, DC USA.
NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2010
VL 70
SU 24
MA P1-07-03
DI 10.1158/0008-5472.SABCS10-P1-07-03
PG 1
WC Oncology
SC Oncology
GA V43QL
UT WOS:000209695800439
ER
PT J
AU Gee, AM
Pfalzer, L
Stout, N
Levy, E
McGarvey, C
Springer, B
Soballe, P
Gerber, L
AF Gee, A. Morehead
Pfalzer, L.
Stout, N.
Levy, E.
McGarvey, C.
Springer, B.
Soballe, P.
Gerber, L.
TI Racial Disparities in Physical and Functional Domains in Women with
Early Breast Cancer
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 NIH, Bethesda, MD 20892 USA.
Univ Michigan, Flint, MI 48503 USA.
Natl Naval Med Ctr, Bethesda, MD USA.
CLM Consulting, Rockville, MD USA.
Balboa Naval Hosp, San Diego, CA USA.
George Mason Univ, Fairfax, VA 22030 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2010
VL 70
SU 24
MA P1-10-06
DI 10.1158/0008-5472.SABCS10-P1-10-06
PG 1
WC Oncology
SC Oncology
GA V43QL
UT WOS:000209695800458
ER
PT J
AU Gomez, J
AF Gomez, J.
TI Molecular Profiling of Stage II and Ill Breast Cancer in Latin American
Women Receiving Standard-of-Care Treatment
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Gomez, J.] NCI, NIH, OD, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2010
VL 70
SU 24
MA P6-04-16
DI 10.1158/0008-5472.SABCS10-P6-04-16
PG 1
WC Oncology
SC Oncology
GA V43QL
UT WOS:000209695800237
ER
PT J
AU Heckman-Stoddard, BM
Grubbs, CJ
Johnson, K
Lubet, RA
AF Heckman-Stoddard, B. M.
Grubbs, C. J.
Johnson, K.
Lubet, R. A.
TI Doses of Selective Estrogen Receptor Modulations (SERMS) Required for
Prevention and Therapy of Chemically-Induced Mammary Cancers
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 NCI, Bethesda, MD 20892 USA.
Univ Alabama Birmingham, Birmingham, AL USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2010
VL 70
SU 24
MA P1-08-04
DI 10.1158/0008-5472.SABCS10-P1-08-04
PG 1
WC Oncology
SC Oncology
GA V43QL
UT WOS:000209695800443
ER
PT J
AU Ingle, JN
Liu, M
Wickerham, DL
Schaid, DJ
Mushiroda, T
Kubo, M
Costantino, JP
Goetz, MP
Ames, MM
Wang, L
Vogel, VG
Paik, S
Batzler, A
Flockhart, DA
Wolmark, N
Nakamura, Y
Weinshilboum, R
AF Ingle, J. N.
Liu, M.
Wickerham, D. L.
Schaid, D. J.
Mushiroda, T.
Kubo, M.
Costantino, J. P.
Goetz, M. P.
Ames, M. M.
Wang, L.
Vogel, V. G.
Paik, S.
Batzler, A.
Flockhart, D. A.
Wolmark, N.
Nakamura, Y.
Weinshilboum, R.
TI Genome-Wide Associations of Breast Events and Functional Genomic Studies
in High-Risk Women Receiving Tamoxifen or Raloxifene on NSABP P1 and P2
Prevention Trials. A Pharmacogenomics Research Network-RIKEN-NSABP
Collaboration
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 Mayo Clin, Rochester, MN USA.
NSABP, Pittsburgh, PA USA.
RIKEN, Tokyo, Japan.
Indiana Univ, Indianapolis, IN 46204 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2010
VL 70
SU 24
MA PD05-02
DI 10.1158/0008-5472.SABCS10-PD05-02
PG 2
WC Oncology
SC Oncology
GA V43QL
UT WOS:000209695801408
ER
PT J
AU Lee, MP
Kadota, M
Yang, HH
Clifford, RJ
Dunn, BK
AF Lee, M. P.
Kadota, M.
Yang, H. H.
Clifford, R. J.
Dunn, B. K.
TI Novel Genome-Wide DNA Methylation Signatures of Primary Breast Tumor
Subtypes
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Lee, M. P.; Kadota, M.; Yang, H. H.; Clifford, R. J.; Dunn, B. K.] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2010
VL 70
SU 24
MA P3-04-04
DI 10.1158/0008-5472.SABCS10-P3-04-04
PG 1
WC Oncology
SC Oncology
GA V43QL
UT WOS:000209695801193
ER
PT J
AU Lubet, RA
Iwata, K
Szabo, E
Grubbs, CJ
AF Lubet, R. A.
Iwata, K.
Szabo, E.
Grubbs, C. J.
TI Alternative Dosing Regimens with Tarceva in a Mammary Cancer Model:
Effects on Efficacy and Potential Effects on Toxicity
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 NCI, Bethesda, MD 20892 USA.
OSI Pharmaceut, Farmingdale, NY USA.
Univ Alabama Birmingham, Birmingham, AL USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2010
VL 70
SU 24
MA P1-08-03
DI 10.1158/0008-5472.SABCS10-P1-08-03
PG 1
WC Oncology
SC Oncology
GA V43QL
UT WOS:000209695800442
ER
PT J
AU McShane, LM
AF McShane, L. M.
TI Statistical Challenges in Predictive and Prognostic Biomarker Studies:
How To Avoid Wasting Your Time and Specimens
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [McShane, L. M.] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2010
VL 70
SU 24
MA ES4-1
DI 10.1158/0008-5472.SABCS10-ES4-1
PG 1
WC Oncology
SC Oncology
GA V43QL
UT WOS:000209695800362
ER
PT J
AU Nyante, SJ
Faupel-Badger, JM
Sherman, ME
Gaudet, MM
Falk, RT
Andaya, AA
Pfeiffer, RM
Lissowska, J
Brinton, LA
Peplonska, B
Vonderhaar, BK
Chanock, SJ
Garcia-Closas, M
Figueroa, JD
AF Nyante, S. J.
Faupel-Badger, J. M.
Sherman, M. E.
Gaudet, M. M.
Falk, R. T.
Andaya, A. A.
Pfeiffer, R. M.
Lissowska, J.
Brinton, L. A.
Peplonska, B.
Vonderhaar, B. K.
Chanock, S. J.
Garcia-Closas, M.
Figueroa, J. D.
TI Genetic Variation in Prolactin and Prolactin Receptor, and Relationships
with Serum Prolactin Levels and Breast Cancer Risk
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 NCI, Bethesda, MD 20892 USA.
Albert Einstein Coll Med, New York, NY USA.
Ctr Canc, Warsaw, Poland.
M Sklodowska Curie Inst Oncol, Warsaw, Poland.
Nofer Inst Occupat Med, Lodz, Poland.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2010
VL 70
SU 24
MA P3-12-05
DI 10.1158/0008-5472.SABCS10-P3-12-05
PG 1
WC Oncology
SC Oncology
GA V43QL
UT WOS:000209695801274
ER
PT J
AU Sgroi, DC
Finkelstein, DM
Shepherd, L
Ingle, JN
Rimm, DL
Sasano, H
Porter, P
Pins, M
Paik, S
Ristimaki, A
Pritchard, KI
Tu, D
Goss, PE
AF Sgroi, D. C.
Finkelstein, D. M.
Shepherd, L.
Ingle, J. N.
Rimm, D. L.
Sasano, H.
Porter, P.
Pins, M.
Paik, S.
Ristimaki, A.
Pritchard, K. I.
Tu, D.
Goss, P. E.
TI Quantitative Protein and Gene Expression Biomarkers of Tamoxifen and
Letrozole Recurrence in the NCIC CTG MA.17 Cohort
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Queens Univ, Kingston, ON, Canada.
Mayo Clin, Rochester, MN USA.
Yale Univ, Sch Med, New Haven, CT USA.
Tohoku Univ, Sch Med, Sendai, Miyagi 980, Japan.
Univ Washington Med, Seattle, WA USA.
Advocate Lutheran Gen Hosp, Park Ridge, IL USA.
Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA.
Univ Helsinki, FIN-00014 Helsinki, Finland.
Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2010
VL 70
SU 24
MA P3-10-26
DI 10.1158/0008-5472.SABCS10-P3-10-26
PG 1
WC Oncology
SC Oncology
GA V43QL
UT WOS:000209695801237
ER
PT J
AU Simone, NL
Dan, TD
Smith, SL
Shih, JH
Lita, E
Sciuto, L
Danforth, D
Camphausen, K
AF Simone, N. L.
Dan, T. D.
Smith, S. L.
Shih, J. H.
Lita, E.
Sciuto, L.
Danforth, D.
Camphausen, K.
TI Twenty-Five Year Results in the Treatment of Early Breast Carcinoma with
Mastectomy Versus Breast Conservation Therapy: The National Cancer
Institute Randomized Trial
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 NCI, NIH, Bethesda, MD 20892 USA.
NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2010
VL 70
SU 24
MA P4-10-01
DI 10.1158/0008-5472.SABCS10-P4-10-01
PG 1
WC Oncology
SC Oncology
GA V43QL
UT WOS:000209695800109
ER
PT J
AU Tang, G
Costantino, JP
Crager, M
Shak, S
Wolmark, N
AF Tang, G.
Costantino, J. P.
Crager, M.
Shak, S.
Wolmark, N.
TI Comparing the Prediction of Chemotherapy Benefit in Patients with
Node-Negative, ER-Positive Breast Cancer Using the Recurrence Score and
a New Measure That Integrates Clinical and Pathologic Factors with the
Recurrence Score
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 NSABP, Pittsburgh, PA USA.
Genom Hlth Inc, Redwood City, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2010
VL 70
SU 24
MA S4-9
DI 10.1158/0008-5472.SABCS10-S4-9
PG 2
WC Oncology
SC Oncology
GA V43QL
UT WOS:000209695802018
ER
PT J
AU Zielinski, R
Lyakhov, I
Hassan, M
Kuban, M
Shafer-Weaver, K
Capala, J
AF Zielinski, R.
Lyakhov, I.
Hassan, M.
Kuban, M.
Shafer-Weaver, K.
Capala, J.
TI Affitoxin - A Potent Therapeutic Agent for Treatment of
HER2-Overexpressing Tumors
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 NCI, NIH, Bethesda, MD 20892 USA.
SAIC Frederick Inc, NCI Frederick, Frederick, MD USA.
Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD DEC 15
PY 2010
VL 70
SU 24
MA P3-14-23
DI 10.1158/0008-5472.SABCS10-P3-14-23
PG 1
WC Oncology
SC Oncology
GA V43QL
UT WOS:000209695801312
ER
PT J
AU Wu, JJ
Quijano, C
Wang, JM
Finkel, T
AF Wu, J. Julie
Quijano, Celia
Wang, Jiamei
Finkel, Toren
TI Metabolism meets autophagy
SO CELL CYCLE
LA English
DT Editorial Material
ID BETA-CELL MASS; STRESS
C1 [Wu, J. Julie; Quijano, Celia; Wang, Jiamei; Finkel, Toren] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA.
RP Finkel, T (reprint author), NHLBI, Ctr Mol Med, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM finkelt@nih.gov
NR 9
TC 5
Z9 5
U1 0
U2 1
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD DEC 15
PY 2010
VL 9
IS 24
BP 4780
EP 4781
DI 10.4161/cc.9.24.14273
PG 2
WC Cell Biology
SC Cell Biology
GA 695AQ
UT WOS:000285343400006
PM 21150322
ER
PT J
AU Bates, SE
AF Bates, Susan E.
TI Striving to Improve Outcomes in Oncology: Unmet Expectations in a
Complex Disease
SO CLINICAL CANCER RESEARCH
LA English
DT Editorial Material
C1 NCI, Bethesda, MD 20892 USA.
RP Bates, SE (reprint author), NCI, Bethesda, MD 20892 USA.
NR 1
TC 1
Z9 1
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD DEC 15
PY 2010
VL 16
IS 24
BP 5950
EP 5950
DI 10.1158/1078-0432.CCR-10-2940
PG 1
WC Oncology
SC Oncology
GA 695YJ
UT WOS:000285408600007
PM 21169246
ER
PT J
AU Yu, P
Steel, JC
Zhang, ML
Morris, JC
Waldmann, TA
AF Yu, Ping
Steel, Jason C.
Zhang, Meili
Morris, John C.
Waldmann, Thomas A.
TI Simultaneous Blockade of Multiple Immune System Inhibitory Checkpoints
Enhances Antitumor Activity Mediated by Interleukin-15 in a Murine
Metastatic Colon Carcinoma Model
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID CD8(+) T-CELLS; CHRONIC VIRAL-INFECTION; NATURAL-KILLER; REGULATORY T;
PD-1; IL-15; RECEPTOR; IMMUNOTHERAPY; ACTIVATION; EXPRESSION
AB Purpose: Interleukin 15 (IL-15) is a promising cytokine for immunotherapy of cancer due to its ability to stimulate the immunity of natural killer, B, and T cells. Its effectiveness, however, may be limited by inhibitory checkpoints and pathways that can attenuate immune responses. Finding strategies to abrogate these negative regulators and enhance the efficacy of IL-15 is a critical challenge.
Experimental Design: In a preclinical study, we evaluated IL-15 combined with antibodies to block the negative immune regulators cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed death ligand 1 (PD-L1) in a metastatic murine CT26 colon carcinoma model.
Results: IL-15 treatment resulted in a significant prolongation of survival in mice with metastatic tumor. Administration of IL-15, however, also increased expression of PD-1 on the surface of CD8(+) T cells including CD8(+)CD44(high) memory phenotype T cells. Moreover, IL-15 also increased the secretion of the immunosuppressive cytokine, IL-10. Combining IL-15 with anti-PD-L1 and anti-CTLA-4 (multiple immune checkpoint blockade) exhibited greater CTL killing and IFN gamma secretion. Moreover, this combination resulted in a significant reduction in surface expression of PD-1 on CD8(+) T cells, a decrease in IL-10 secretion, and led to significantly longer survival of tumor-bearing animals compared with mice treated with IL-15 alone or combined singularly with anti-PD-L1 or anti-CTLA-4.
Conclusions: Combining the immune stimulatory properties of IL-15 with the simultaneous removal of 2 critical immune system inhibitory checkpoints, we showed enhancement of immune responses leading to increased antitumor activity. Clin Cancer Res; 16(24); 6019-28. (C) 2010 AACR.
C1 [Yu, Ping; Steel, Jason C.; Zhang, Meili; Morris, John C.; Waldmann, Thomas A.] NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Zhang, Meili] NCI, Lab Anim Sci Program, SAIC Frederick Inc, Frederick, MD 21701 USA.
RP Waldmann, TA (reprint author), NCI, Metab Branch, Ctr Canc Res, Bldg 10,Room 4N115,10 Ctr Dr, Bethesda, MD 20892 USA.
EM tawald@mail.nih.gov
RI Steel, Jason/D-1805-2013
OI Steel, Jason/0000-0003-3608-7542
FU NIH, National Cancer Institute, Center for Cancer Research
FX This work was supported by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research.
NR 38
TC 75
Z9 76
U1 1
U2 10
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD DEC 15
PY 2010
VL 16
IS 24
BP 6019
EP 6028
DI 10.1158/1078-0432.CCR-10-1966
PG 10
WC Oncology
SC Oncology
GA 695YJ
UT WOS:000285408600017
PM 20924130
ER
PT J
AU Jamal, M
Rath, BH
Williams, ES
Camphausen, K
Tofilon, PJ
AF Jamal, Muhammad
Rath, Barbara H.
Williams, Eli S.
Camphausen, Kevin
Tofilon, Philip J.
TI Microenvironmental Regulation of Glioblastoma Radioresponse
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID TUMOR STEM-CELLS; HISTONE H2AX PHOSPHORYLATION; INITIATING CELLS; STRAND
BREAKS; DNA-DAMAGE; X-RAYS; LINES; CANCER; RADIOTHERAPY;
RADIOSENSITIVITY
AB Purpose: Brain tumor xenografts initiated from human glioblastoma (GBM) stem-like cells (TSC) simulate the biological characteristics of GBMs in situ. Therefore, to determine whether the brain microenvironment affects the intrinsic radiosensitivity of GBM cells, we compared the radioresponse of GBM TSCs grown in vitro and as brain tumor xenografts.
Experimental Design: As indicators of DNA double-strand breaks (DSB), gamma H2AX, and 53BP1 foci were defined after irradiation of 2 GBM TSC lines grown in vitro and as orthotopic xenografts in nude mice. Microarray analysis was conducted to compare gene expression patterns under each growth condition.
Results: Dispersal of radiation-induced gamma H2AX and 53BP1 foci was faster in the tumor cells grown as orthotopic xenografts compared with cells irradiated in vitro. In addition, cells irradiated in vivo were approximately 3-fold less susceptible to foci induction as compared with cells grown in vitro. Microarray analysis revealed a significant number of genes whose expression was commonly affected in the 2 GBM models by orthotopic growth conditions. Consistent with the decrease in sensitivity to foci induction, genes related to reactive oxygen species (ROS) metabolism were expressed at higher levels in the brain tumor xenografts.
Conclusion: gamma H2AX and 53BP1 foci analyses indicate that GBM cells irradiated within orthotopic xenografts have a greater capacity to repair DSBs and are less susceptible to their induction than tumor cells irradiated under in vitro growth conditions. Because DSB induction and repair are critical determinants of radiosensitivity, these results imply that the brain microenvironment contributes to GBM radioresistance. Clin Cancer Res; 16(24); 6049-59. (C) 2010 AACR.
C1 [Tofilon, Philip J.] H Lee Moffitt Canc Ctr & Res Inst, Drug Discovery Dept, DRDIS SRB3, Tampa, FL 33612 USA.
[Camphausen, Kevin] NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA.
RP Tofilon, PJ (reprint author), H Lee Moffitt Canc Ctr & Res Inst, Drug Discovery Dept, DRDIS SRB3, 12902 Magnolia Dr, Tampa, FL 33612 USA.
EM philip.tofilon@moffitt.org
FU National Institute of Health [CA138519]; National Cancer Institute
FX This work was supported by grant CA138519 from the National Institute of
Health (P.J.T.) and a Cancer Center Support Grant issued to Moffitt
Cancer Center from the National Cancer Institute.
NR 36
TC 31
Z9 31
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD DEC 15
PY 2010
VL 16
IS 24
BP 6049
EP 6059
DI 10.1158/1078-0432.CCR-10-2435
PG 11
WC Oncology
SC Oncology
GA 695YJ
UT WOS:000285408600020
PM 21037023
ER
PT J
AU Dudley, ME
Gross, CA
Langhan, MM
Garcia, MR
Sherry, RM
Yang, JC
Phan, GQ
Kammula, US
Hughes, MS
Citrin, DE
Restifo, NP
Wunderlich, JR
Prieto, PA
Hong, JJ
Langan, RC
Zlott, DA
Morton, KE
White, DE
Laurencot, CM
Rosenberg, SA
AF Dudley, Mark E.
Gross, Colin A.
Langhan, Michelle M.
Garcia, Marcos R.
Sherry, Richard M.
Yang, James C.
Phan, Giao Q.
Kammula, Udai S.
Hughes, Marybeth S.
Citrin, Deborah E.
Restifo, Nicholas P.
Wunderlich, John R.
Prieto, Peter A.
Hong, Jenny J.
Langan, Russell C.
Zlott, Daniel A.
Morton, Kathleen E.
White, Donald E.
Laurencot, Carolyn M.
Rosenberg, Steven A.
TI CD8+ Enriched "Young" Tumor Infiltrating Lymphocytes Can Mediate
Regression of Metastatic Melanoma
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID CD8(+) T-CELLS; TRANSFER THERAPY; CD8-T-CELL MEMORY; ADOPTIVE TRANSFER;
CD4-T-CELL HELP; CANCER; SURVIVAL; PERSISTENCE; IMMUNOTHERAPY;
AUTOIMMUNITY
AB Purpose: Tumor-infiltrating lymphocytes (TIL) and interleukin (IL)-2 administered following lymphodepletion can cause the durable complete regression of bulky metastatic melanoma in patients refractory to approved treatments. However, the generation of a unique tumor-reactive TIL culture for each patient may be prohibitively difficult. We therefore investigated the clinical and immunologic impact of unscreened, CD8+ enriched "young" TIL.
Experimental Design: Methods were developed for generating TIL that minimized the time in culture and eliminated the individualized tumor-reactivity screening step. Thirty-three patients were treated with these CD8+ enriched young TIL and IL-2 following nonmyeloablative lymphodepletion (NMA). Twenty-three additional patients were treated with CD8+ enriched young TIL and IL-2 after lymphodepletion with NMA and 6 Gy of total body irradiation.
Results: Young TIL cultures for therapy were successfully established from 83% of 122 consecutive melanoma patients. Nineteen of 33 patients (58%) treated with CD8+ enriched young TIL and NMA had an objective response (Response Evaluation Criteria in Solid Tumors) including 3 complete responders. Eleven of 23 patients (48%) treated with TIL and 6 Gy total body irradiation had an objective response including 2 complete responders. At 1 month after TIL infusion the absolute CD8+ cell numbers in the periphery were highly correlated with response.
Conclusions: This study shows that a rapid and simplified method can be used to reliably generate CD8+ enriched young TIL for administration as an individualized therapy for advanced melanoma, and may allow this potentially effective treatment to be applied at other institutions and to reach additional patients. Clin Cancer Res; 16(24); 6122-31. (C) 2010 AACR.
C1 [Dudley, Mark E.; Gross, Colin A.; Langhan, Michelle M.; Garcia, Marcos R.; Sherry, Richard M.; Yang, James C.; Phan, Giao Q.; Kammula, Udai S.; Hughes, Marybeth S.; Restifo, Nicholas P.; Wunderlich, John R.; Prieto, Peter A.; Hong, Jenny J.; Langan, Russell C.; Morton, Kathleen E.; White, Donald E.; Laurencot, Carolyn M.; Rosenberg, Steven A.] NCI, Surg Branch, Bethesda, MD 20892 USA.
[Citrin, Deborah E.] NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA.
[Zlott, Daniel A.] NIH, Dept Pharm, Clin Res Ctr, Bethesda, MD 20892 USA.
RP Dudley, ME (reprint author), NCI, Natl Surg Branch, CRC 3W-5752,10 Ctr Dr, Bethesda, MD 20892 USA.
EM med@nih.gov
RI Restifo, Nicholas/A-5713-2008;
OI Gross, Colin/0000-0002-7061-5073; Restifo, Nicholas
P./0000-0003-4229-4580
FU Intramural NIH HHS [Z01 BC011020-01, ZIC BC011020-02]
NR 31
TC 130
Z9 133
U1 1
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD DEC 15
PY 2010
VL 16
IS 24
BP 6122
EP 6131
DI 10.1158/1078-0432.CCR-10-1297
PG 10
WC Oncology
SC Oncology
GA 695YJ
UT WOS:000285408600027
PM 20668005
ER
PT J
AU Hassan, R
Cohen, SJ
Phillips, M
Pastan, I
Sharon, E
Kelly, RJ
Schweizer, C
Weil, S
Laheru, D
AF Hassan, Raffit
Cohen, Steven J.
Phillips, Martin
Pastan, Ira
Sharon, Elad
Kelly, Ronan J.
Schweizer, Charles
Weil, Susan
Laheru, Daniel
TI Phase I Clinical Trial of the Chimeric Anti-Mesothelin Monoclonal
Antibody MORAb-009 in Patients with Mesothelin-Expressing Cancers
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID PANCREATIC-CANCER; OVARIAN-CANCER; PERITONEAL MESOTHELIOMA; RECOMBINANT
IMMUNOTOXIN; DIAGNOSIS; ADENOCARCINOMAS; INFUSION; MARKER; SS1P
AB Purpose: MORAb-009 is a chimeric monoclonal antibody that targets mesothelin, a tumor differentiation antigen overexpressed in pancreatic cancer, ovarian cancer, mesothelioma, and other malignancies. We conducted a phase I clinical trial of MORAb-009 in patients with advanced mesothelin-expressing cancers to determine its safety, dose-limiting toxicity (DLT), and maximum tolerated dose (MTD).
Methods: Cohorts consisting of 3 to 6 subjects each received MORAb-009 intravenously on days 1, 8, 15, and 22 at progressively increasing doses ranging from 12.5 to 400 mg/m(2). Disease evaluation with computed tomography occurred on day 35. Subjects with responding or stable disease could receive additional cycles of MORAb-009.
Results: A total of 24 subjects were treated including 13 mesothelioma, 7 pancreatic cancer, and 4 ovarian cancer patients. The median number of MORAb-009 infusions was 4 (range 1-24 infusions). At the 400 mg/m 2 dose level, 2 subjects experienced DLT (grade 4 transaminitis and a grade 3 serum sickness). Thus, although there were other contributing causes of these adverse events, 200 mg/m(2) was considered the MTD. Other adverse events at least possibly related to MORAb-009 included 7 drug hypersensitivity events (all grade 1 or 2) and a thromboembolic event (grade 4). Eleven subjects had stable disease. There was a dose-dependent increase in serum MORAb-009 concentration.
Conclusion: MORAb-009 is well tolerated and the MTD when administered weekly is conservatively set at 200 mg/m(2). In this group of previously treated patients, 11 subjects had stable disease. Phase II studies of MORAb-009 in different mesothelin-expressing cancers are ongoing. Clin Cancer Res; 16(24); 6132-8. (C)2010 AACR.
C1 [Hassan, Raffit; Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Cohen, Steven J.] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA.
[Phillips, Martin; Schweizer, Charles; Weil, Susan] Morphotek Inc, Exton, PA USA.
[Sharon, Elad; Kelly, Ronan J.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Laheru, Daniel] Johns Hopkins Sch Med, Dept Med Oncol, Sidney Kimmel Canc Ctr, Baltimore, MD USA.
RP Hassan, R (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Rm 5116, Bethesda, MD 20892 USA.
EM hassanr@mail.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research; Morphotek,
Inc.; National Cancer Institute
FX This research was supported in part by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research, and
in part by Morphotek, Inc., under a Cooperative Research and Development
Agreement with National Cancer Institute.
NR 25
TC 75
Z9 76
U1 1
U2 10
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD DEC 15
PY 2010
VL 16
IS 24
BP 6132
EP 6138
DI 10.1158/1078-0432.CCR-10-2275
PG 7
WC Oncology
SC Oncology
GA 695YJ
UT WOS:000285408600028
PM 21037025
ER
PT J
AU Libutti, SK
Paciotti, GF
Byrnes, AA
Alexander, HR
Gannon, WE
Walker, M
Seidel, GD
Yuldasheva, N
Tamarkin, L
AF Libutti, Steven K.
Paciotti, Giulio F.
Byrnes, Adriana A.
Alexander, H. Richard, Jr.
Gannon, William E.
Walker, Melissa
Seidel, Geoffrey D.
Yuldasheva, Nargiza
Tamarkin, Lawrence
TI Phase I and Pharmacokinetic Studies of CYT-6091, a Novel PEGylated
Colloidal Gold-rhTNF Nanomedicine
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID TUMOR-NECROSIS-FACTOR; ISOLATED LIMB PERFUSION; ADVANCED MALIGNANT
DISEASE; SOFT-TISSUE SARCOMA; FACTOR-ALPHA; TNF-ALPHA; INTERFERON-GAMMA;
RTNF-ALPHA; MELPHALAN; TRIAL
AB Purpose: A novel nanomedicine, CYT-6091, constructed by simultaneously binding recombinant human tumor necrosis factor alpha (rhTNF) and thiolyated polyethylene glycol to the surface of 27-nm colloidal gold particles, was tested in a phase I dose escalation clinical trial in advanced stage cancer patients.
Experimental Design: CYT-6091, whose dosing was based on the amount of rhTNF in the nanomedicine, was injected intravenously, and 1 cycle of treatment consisted of 2 treatments administered 14 days apart.
Results: Doses from 50 mu g/m(2) to 600 mu g/m(2) were well tolerated, and no maximum tolerated dose (MTD) was reached, as the highest dose exceeded the target dosage of 1-mg rhTNF per treatment, exceeding the previous MTD for native rhTNF by 3-fold. The first 2 patients on the study, each receiving 50 mu g/m(2), did not receive any prophylactic antipyretics or H2 blockade. A predicted, yet controllable fever occurred in these patients, so all subsequently treated patients received prophylactic antipyretics and H2 blockers. However, even at the highest dose rhTNF's dose-limiting toxic effect of hypotension was not seen. Using electron microscopy to visualize nanoparticles of gold in patient biopsies of tumor and healthy tissue showed that patient biopsies taken 24 hours after treatment had nanoparticles of gold in tumor tissue.
Conclusions: These data indicate that rhTNF formulated as CYT-6091 may be administered systemically at doses of rhTNF that were previously shown to be toxic and that CYT-6091 may target to tumors. Future clinical studies will focus on combining CYT-6091 with approved chemotherapies for the systemic treatment of nonresectable cancers. Clin Cancer Res; 16(24); 6139-49. (C)2010 AACR.
C1 [Paciotti, Giulio F.; Tamarkin, Lawrence] CytImmune Sci Inc, Rockville, MD 20850 USA.
[Libutti, Steven K.; Alexander, H. Richard, Jr.; Walker, Melissa; Yuldasheva, Nargiza] NIH, Surg Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Byrnes, Adriana A.; Seidel, Geoffrey D.] SAIC Frederick Inc, Clin Monitoring Res Program, Natl Canver Inst Frederick, Frederick, MD USA.
[Gannon, William E.] Capital City Tech Consulting Inc, Washington, DC USA.
RP Tamarkin, L (reprint author), CytImmune Sci Inc, 9640 Med Ctr Dr, Rockville, MD 20850 USA.
EM ltamarkin@cytimmune.com
FU National Cancer Institute; National Institutes of Health
[HHSN2612008000001E]
FX This project has been funded in part with federal funds from the
National Cancer Institute, National Institutes of Health, under Contract
No. HHSN2612008000001E.
NR 41
TC 210
Z9 216
U1 10
U2 39
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD DEC 15
PY 2010
VL 16
IS 24
BP 6139
EP 6149
DI 10.1158/1078-0432.CCR-10-0978
PG 11
WC Oncology
SC Oncology
GA 695YJ
UT WOS:000285408600029
PM 20876255
ER
PT J
AU Cohen, C
Simonsen, L
Kang, JW
Miller, M
McAnerney, J
Blumberg, L
Schoub, B
Madhi, SA
Viboud, C
AF Cohen, Cheryl
Simonsen, Lone
Kang, Jong-Won
Miller, Mark
McAnerney, Jo
Blumberg, Lucille
Schoub, Barry
Madhi, Shabir A.
Viboud, Cecile
TI Elevated Influenza-Related Excess Mortality in South African Elderly
Individuals, 1998-2005
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID RESPIRATORY SYNCYTIAL VIRUS; UNITED-STATES; HONG-KONG; PANDEMIC
INFLUENZA; VACCINATION; PNEUMONIA; IMPACT; EPIDEMICS; DEATHS; AGE
AB Background. Although essential to guide control measures, published estimates of influenza-related seasonal mortality for low-and middle-income countries are few. We aimed to compare influenza-related mortality among individuals aged >= 65 years in South Africa and the United States.
Methods. We estimated influenza-related excess mortality due to all causes, pneumonia and influenza, and other influenza-associated diagnoses from monthly age-specific mortality data for 1998-2005 using a Serfling regression model. We controlled for between-country differences in population age structure and nondemographic factors (baseline mortality and coding practices) by generating age-standardized estimates and by estimating the percentage excess mortality attributable to influenza.
Results. Age-standardized excess mortality rates were higher in South Africa than in the United States: 545 versus 133 deaths per 100,000 population for all causes(P < .001) and 63 vs 21 deaths per 100,000 population for pneumonia and influenza (P = .03). Standardization for nondemographic factors decreased but did not eliminate between-country differences; for example, the mean percentage of winter deaths attributable to influenza was 16% in South Africa and 6% in the United States (P < .001). For all respiratory causes, cerebrovascular disease, and diabetes, age-standardized excess death rates were 4-8-fold greater in South Africa than in the United States, and the percentage increase in winter deaths attributable to influenza was 2-4-fold higher.
Conclusions. These data suggest that the impact of seasonal influenza on mortality among elderly individuals may be substantially higher in an African setting, compared with in the United States, and highlight the potential for influenza vaccination programs to decrease mortality.
C1 [Cohen, Cheryl; McAnerney, Jo; Blumberg, Lucille; Schoub, Barry] Univ Witwatersrand, Natl Hlth Lab Serv, Natl Inst Communicable Dis, Johannesburg, South Africa.
[Cohen, Cheryl] Univ Witwatersrand, Sch Publ Hlth, Johannesburg, South Africa.
[Schoub, Barry; Madhi, Shabir A.] Univ Witwatersrand, Sch Pathol, Johannesburg, South Africa.
[Madhi, Shabir A.] Univ Witwatersrand, Dept Sci & Technol, Natl Res Fdn Vaccine Preventable Dis, Johannesburg, South Africa.
[Simonsen, Lone] George Washington Univ, Washington, DC USA.
[Simonsen, Lone; Kang, Jong-Won; Miller, Mark; Viboud, Cecile] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Cohen, C (reprint author), Natl Inst Communicable Dis, Epidemiol & Surveillance Unit, Private Bag X4, ZA-2131 Johannesburg, Gauteng, South Africa.
EM cherylc@nicd.ac.za
OI Simonsen, Lone/0000-0003-1535-8526
FU Office of Global Health Affairs' International Influenza Unit in the
Office of the Secretary of the Department of Health and Human Services;
Science and Technology Directorate, Department of Homeland Security;
Fogarty International Center, National Institutes of Health;
Wyeth-Pfizer; SDI Health
FX This research was conducted in the context of the Multinational
Influenza Seasonal Mortality Study (MISMS), an ongoing international
collaborative effort to understand influenza epidemiological and
evolutionary patterns, led by the Fogarty International Center, National
Institutes of Health (http://www.origem.info/misms/index.php). Funding
for this project comes from the Office of Global Health Affairs'
International Influenza Unit in the Office of the Secretary of the
Department of Health and Human Services.; Financial support. Research
and Policy for Infectious Disease Dynamics (RAPIDD) program of the
Science and Technology Directorate, Department of Homeland Security, and
Fogarty International Center, National Institutes of Health (to L.S.).;
L. S. has received funding for a research study from Wyeth-Pfizer and
consulting fees from SDI Health, a data warehouse business in Plymouth
Meeting, PA. All other authors: no conflicts.
NR 43
TC 47
Z9 47
U1 0
U2 5
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD DEC 15
PY 2010
VL 51
IS 12
BP 1362
EP 1369
DI 10.1086/657314
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 681WD
UT WOS:000284353100004
PM 21070141
ER
PT J
AU Uzel, G
Orange, JS
Poliak, N
Marciano, BE
Heller, T
Holland, SM
AF Uzel, Gulbu
Orange, Jordan S.
Poliak, Nina
Marciano, Beatriz E.
Heller, Theo
Holland, Steven M.
TI Complications of Tumor Necrosis Factor-alpha Blockade in Chronic
Granulomatous Disease-Related Colitis
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID CROHNS-DISEASE; INFLIXIMAB THERAPY; RHEUMATOID-ARTHRITIS;
CARINII-PNEUMONIA; INTERFERON-GAMMA; INFECTION; PATIENT; MAINTENANCE;
ANTIBODY; OPTIONS
AB Background. Chronic granulomatous disease (CGD) is a genetic disorder of the phagocyte NADPH oxidase, which predisposes patients to infections and inflammatory complications, including severe colitis. Management of CGD colitis is a challenge because standard immunosuppressive therapy increases the risk of infection in already immunocompromised hosts.
Methods. We report the use of infliximab in 5 patients with CGD.
Results. Infliximab administration predisposed patients to severe infections with typical CGD pathogens but not mycobacteria, as reported with infliximab in other conditions. In addition to infections, infliximab administration led to successful closure of fistulae, sometimes with other untoward consequences. Infliximab-associated complications were associated with 2 deaths.
Conclusions. Infliximab use in the treatment of CGD inflammatory bowel disease requires aggressive antimicrobial prophylaxis, assiduous surveillance for infection, and vigilance for untoward gastrointestinal complications. This experience suggests that infliximab therapy is effective but has untoward consequences in patients with CGD.
C1 [Uzel, Gulbu; Marciano, Beatriz E.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Heller, Theo] NIAID, NIDDKD, NIH, Bethesda, MD 20892 USA.
[Orange, Jordan S.; Poliak, Nina] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Div Immunol, Philadelphia, PA 19104 USA.
RP Uzel, G (reprint author), Bldg 10,CRC B3 4141,MSC 1684, Bethesda, MD 20892 USA.
EM guzel@mail.nih.gov
OI orange, jordan/0000-0001-7117-7725
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health, Bethesda, Maryland
FX Financial support. The Intramural Research Program of the National
Institute of Allergy and Infectious Diseases, National Institutes of
Health, Bethesda, Maryland.
NR 38
TC 39
Z9 39
U1 0
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD DEC 15
PY 2010
VL 51
IS 12
BP 1429
EP 1434
DI 10.1086/657308
PG 6
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 681WD
UT WOS:000284353100014
PM 21058909
ER
PT J
AU Bausch, DG
Hadi, CM
Khan, SH
Lertora, JJL
AF Bausch, Daniel G.
Hadi, Christiane M.
Khan, Sheik Humarr
Lertora, Juan J. L.
TI Review of the Literature and Proposed Guidelines for the Use of Oral
Ribavirin as Postexposure Prophylaxis for Lassa Fever
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Review
ID CHRONIC HEPATITIS-C; ARGENTINE HEMORRHAGIC-FEVER; ANTIVIRAL AGENT
RIBAVIRIN; VIRUS-INFECTION; INTRAVENOUS RIBAVIRIN; EPIDEMIOLOGICAL
ASPECTS; DENDRITIC CELLS; CLINICAL-TRIAL; RENAL-FUNCTION; INDUCED ANEMIA
AB Lassa fever is an acute viral hemorrhagic illness; the virus is endemic in West Africa and also of concern with regard to bioterrorism. Transmission of Lassa virus between humans may occur through direct contact with infected blood or bodily secretions. Oral administration of the antiviral drug ribavirin is often considered for postexposure prophylaxis, but no systematically collected data or uniform guidelines exist for this indication. Furthermore, the relatively low secondary attack rates for Lassa fever, the restriction of the area of endemicity to West Africa, and the infrequency of high-risk exposures make it unlikely that controlled prospective efficacy trials will ever be possible. Recommendations for postexposure use of ribavirin can therefore be made only on the basis of a thorough understanding and logical extrapolation of existing data. Here, we review the pertinent issues and propose guidelines based on extensive review of the literature, as well as our experience in this field. We recommend oral ribavirin postexposure prophylaxis for Lassa fever exclusively for definitive high-risk exposures. These guidelines may also serve for exposure to other hemorrhagic fever viruses susceptible to ribavirin.
C1 [Bausch, Daniel G.] Tulane Univ, Tulane Sch Publ Hlth & Trop Med, Dept Trop Med, Hlth Sci Ctr, New Orleans, LA 70112 USA.
[Lertora, Juan J. L.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Khan, Sheik Humarr] Kenema Govt Hosp, Minist Hlth & Sanitat, Kenema, Sierra Leone.
RP Bausch, DG (reprint author), Tulane Univ, Tulane Sch Publ Hlth & Trop Med, Dept Trop Med, Hlth Sci Ctr, SL-17,1430 Tulane Ave, New Orleans, LA 70112 USA.
EM dbausch@tulane.edu
FU Tulane University
FX Financial support. Tulane University.
NR 86
TC 43
Z9 44
U1 2
U2 17
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD DEC 15
PY 2010
VL 51
IS 12
BP 1435
EP 1441
DI 10.1086/657315
PG 7
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 681WD
UT WOS:000284353100015
PM 21058912
ER
PT J
AU Morens, DM
Taubenberger, JK
Folkers, GK
Fauci, AS
AF Morens, David M.
Taubenberger, Jeffery K.
Folkers, Gregory K.
Fauci, Anthony S.
TI Pandemic Influenza's 500th Anniversary
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Editorial Material
AB It is impossible to know with certainty the first time that an influenza virus infected humans or when the first influenza pandemic occurred. However, many historians agree that the year 1510 A.D.-500 years ago-marks the first recognition of pandemic influenza. On this significant anniversary it is timely to ask: what were the circumstances surrounding the emergence of the 1510 pandemic, and what have we learned about this important disease over the subsequent five centuries? We conclude that in recent decades significant progress has been made in diagnosis, prevention, control, and treatment of influenza. It seems likely that, in the foreseeable future, we may be able to greatly reduce the burden of influenza pandemics with improved vaccines and other scientific and public health approaches.
C1 [Morens, David M.; Taubenberger, Jeffery K.; Folkers, Gregory K.; Fauci, Anthony S.] NIAID, NIH, Bethesda, MD 20892 USA.
RP Morens, DM (reprint author), NIAID, NIH, Bldg 31,Rm 7A-03,31 Ctr Dr, Bethesda, MD 20892 USA.
EM dm260q@nih.gov
FU Intramural NIH HHS
NR 15
TC 16
Z9 17
U1 0
U2 4
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD DEC 15
PY 2010
VL 51
IS 12
BP 1442
EP 1444
DI 10.1086/657429
PG 3
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 681WD
UT WOS:000284353100016
PM 21067353
ER
PT J
AU Balamurugan, K
Wang, JM
Tsai, HH
Sharan, S
Anver, M
Leighty, R
Sterneck, E
AF Balamurugan, Kuppusamy
Wang, Ju-Ming
Tsai, Hsin-Hwa
Sharan, Shikha
Anver, Miriam
Leighty, Robert
Sterneck, Esta
TI The tumour suppressor C/EBP delta inhibits FBXW7 expression and promotes
mammary tumour metastasis
SO EMBO JOURNAL
LA English
DT Article
DE hypoxia; mammary tumour; metastasis; protein stability; protein
translation
ID BINDING-PROTEIN-DELTA; CELL-CYCLE ARREST; HYPOXIA-INDUCIBLE FACTORS;
GENE-EXPRESSION; BREAST-CANCER; INNATE IMMUNITY; FACTOR-1 HIF-1;
FANCONI-ANEMIA; HIF-1-ALPHA; PATHWAY
AB Inflammation and hypoxia are known to promote the metastatic progression of tumours. The CCAAT/enhancer-binding protein-delta (C/EBP delta, CEBPD) is an inflammatory response gene and candidate tumour suppressor, but its physiological role in tumourigenesis in vivo is unknown. Here, we demonstrate a tumour suppressor function of C/EBP delta using transgenic mice overexpressing the Neu/Her2/ERBB2 proto-oncogene in the mammary gland. Unexpectedly, this study also revealed that C/EBP delta is necessary for efficient tumour metastasis. We show that C/EBP delta is induced by hypoxia in tumours in vivo and in breast tumour cells in vitro, and that C/EBP delta-deficient cells exhibit reduced glycolytic metabolism and cell viability under hypoxia. C/EBP delta supports CXCR4 expression. On the other hand, C/EBP delta directly inhibits expression of the tumour suppressor F-box and WD repeat-domain containing 7 gene (FBXW7, FBW7, AGO, Cdc4), encoding an F-box protein that promotes degradation of the mammalian target of rapamycin (mTOR). Consequently, C/EBP delta enhances mTOR/AKT/S6K1 signalling and augments translation and activity of hypoxia-inducible factor-1 alpha (HIF-1 alpha), which is necessary for hypoxia adaptation. This work provides new insight into the mechanisms by which metastasis-promoting signals are induced specifically under hypoxia. The EMBO Journal (2010) 29, 4106-4117. doi: 10.1038/emboj.2010.280; Published online 12 November 2010
C1 [Balamurugan, Kuppusamy; Sharan, Shikha; Sterneck, Esta] NCI, Lab Cell & Dev Signalling, CCR, Frederick, MD 21702 USA.
[Wang, Ju-Ming; Tsai, Hsin-Hwa] Natl Cheng Kung Univ, Coll Biosci & Biotechnol, Inst Bioinformat & Biosignal Transduct, Tainan 70101, Taiwan.
[Anver, Miriam] NCI, Pathol Histotechnol Lab, SAIC Frederick, Frederick, MD 21702 USA.
[Leighty, Robert] NCI, Data Management Serv Inc, Frederick, MD 21702 USA.
RP Sterneck, E (reprint author), NCI, Lab Cell & Dev Signalling, CCR, 1050 Boyles St,Bldg 560, Frederick, MD 21702 USA.
EM sternecg@mail.nih.gov
FU NIH, National Cancer Institute; Federal Funds [HHSN261200800001E]
FX We are indebted to Glenn Summers and the SAIC Animal Sciences Program
for outstanding technical support, Donna Butcher for superb
immunohistochemistry services, Linda Miller for genotyping, Simona
Florea for quantification of lung metastases, Melinda Hollingshead for
teaching us tumour cell isolation and Stephen Lockett and Larry
Sternberg for help with image capture and analysis. For generously
providing reagents, we thank Giovanni Mellilo and Annamaria Rapisarda
(U251-HRE cells), Valery Bliskovsky and Beverly Mock (mTOR expression
construct) and William Muller and Jeff Green (MMTV-c-Neu transgenic
mice). We thank Debbie Liao and Randall S Johnson for advice and sharing
unpublished data. We thank Douglas Lowy, Lalage Wakefield, Giovanni
Melillo, Ira Daar, Jun Wang and Tapasree Roy Sarkar for invaluable
discussion and critical comments on the paper, and Richard Frederickson
for preparation of the figures. This research was supported by the
Intramural Research Program of the NIH, National Cancer Institute and,
in part, by Federal Funds under contract no. HHSN261200800001E.
Balamurugan, Sterneck and Wang planned the experiments; Balamurugan,
Wang, Tsai and Sharan executed experiments; Balamurugan, Sterneck,
Leighty, Anver and Wang analysed the data; and Balamurugan and Sterneck
wrote the paper.
NR 69
TC 52
Z9 53
U1 1
U2 11
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 DEC 15
PY 2010
VL 29
IS 24
BP 4106
EP 4117
DI 10.1038/emboj.2010.280
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 695XX
UT WOS:000285407200007
PM 21076392
ER
PT J
AU Schecter, A
Malik, N
Haffner, D
Smith, S
Harris, TR
Paepke, O
Birnbaum, L
AF Schecter, Arnold
Malik, Noor
Haffner, Darrah
Smith, Sarah
Harris, T. Robert
Paepke, Olaf
Birnbaum, Linda
TI Bisphenol A (BPA) in U.S. Food
SO ENVIRONMENTAL SCIENCE & TECHNOLOGY
LA English
DT Article
ID PERFORMANCE LIQUID-CHROMATOGRAPHY; IN-UTERO EXPOSURE; DEVELOPMENTAL
EXPOSURE; RISK-ASSESSMENT; CANNED FOODS; HUMAN HEALTH; BREAST-MILK;
MIGRATION; MICE; COATINGS
AB Bisphenol A (BPA) is a chemical used for lining metal cans and in polycarbonate plastics, such as baby bottles. In rodents, BPA is associated with early sexual maturation, altered behavior, and effects on prostate and mammary glands. In humans, BPA is associated with cardiovascular disease, diabetes, and male sexual dysfunction in exposed workers. Food is a major exposure source. We know of no studies reporting BPA in U.S. fresh food, canned food, and food in plastic packaging in peer reviewed journals. We measured BPA levels in 105 fresh and canned foods, foods sold in plastic packaging, and in cat and dog foods in cans and plastic packaging. We detected BPA in 63 of 105 samples, including fresh turkey, canned green beans, and canned infant formula. Ninety-three of these samples were triplicates which had similar detected levels. Detected levels ranged from 0.23 to 65.0 ng/g ww and were not associated with type of food or packaging but did vary with pH. BPA levels were higher for foods of pH 5 compared to more acidic and alkaline foods. Detected levels were comparable to those found by others. Further research is indicated to determine BPA levels in U.S. food in larger, representative sampling.
C1 [Schecter, Arnold; Malik, Noor; Smith, Sarah; Harris, T. Robert] Univ Texas Dallas, Sch Publ Hlth, Dallas, TX 75390 USA.
[Haffner, Darrah] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Birnbaum, Linda] NCI, Bethesda, MD 20892 USA.
[Paepke, Olaf] Eurofins Gfa GmbH Lab, D-21079 Hamburg, Germany.
RP Schecter, A (reprint author), Univ Texas Dallas, Sch Publ Hlth, 6011 Harry Hines Blvd,V8-112, Dallas, TX 75390 USA.
EM Arnold.Schecter@UTSouthwestern.edu
OI zaraat, javad/0000-0001-5341-7481
FU Gustavus and Louise Pfeiffer Research Foundation
FX This study was funded by a grant from the Gustavus and Louise Pfeiffer
Research Foundation. We thank Consumers Union and the Environmental
Working Group for generously sharing their findings with us. Disclaimer:
This manuscript does not reflect NIEHS/NIH policy.
NR 53
TC 103
Z9 108
U1 10
U2 76
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0013-936X
J9 ENVIRON SCI TECHNOL
JI Environ. Sci. Technol.
PD DEC 15
PY 2010
VL 44
IS 24
BP 9425
EP 9430
DI 10.1021/es102785d
PG 6
WC Engineering, Environmental; Environmental Sciences
SC Engineering; Environmental Sciences & Ecology
GA 694AK
UT WOS:000285266900030
PM 21038926
ER
PT J
AU Germain, RN
AF Germain, Ronald N.
TI Computational analysis of T cell receptor signaling and ligand
discrimination - Past, present, and future
SO FEBS LETTERS
LA English
DT Review
DE T Cell receptor; Receptor signaling; T Lymphocyte; Computational
modeling; Antigen discrimination
ID CYTOPLASMIC FREE CALCIUM; IMMUNOLOGICAL SYNAPSE; ANTIGEN RECEPTOR;
IMMUNE-SYSTEM; ANTAGONIST LIGANDS; NEGATIVE FEEDBACK; CUTTING EDGE;
ACTIVATION; COMPLEX; PROTEIN
AB Signaling through the T cell receptor for antigen (TCR) has been studied for years by conventional biochemical means. More recently, attempts have been made to develop computational models of signaling through this receptor, with a specific focus on understanding how this recognition system discriminates between closely related (self and non-self) ligands. Here we discuss recent advances centered on the role of feedback regulation, especially the key finding that a combination of digital and analog control circuits is fundamental to the discrimination properties of the TCR. We end by pointing to future, more biologically accurate models that incorporate spatial aspects of molecular organization in antigen-engaged T lymphocytes with this underlying biochemistry. Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.
C1 NIAID, Lymphocyte Biol Sect,Trans NIH Ctr Human Immunol, Immunol Lab,NIH,DHHS, Program Syst Immunol & Infect Dis Modeling PSIIM, Bethesda, MD 20892 USA.
RP Germain, RN (reprint author), NIAID, Lymphocyte Biol Sect,Trans NIH Ctr Human Immunol, Immunol Lab,NIH,DHHS, Program Syst Immunol & Infect Dis Modeling PSIIM, Bldg 10,Rm 11N311,10 Ctr Dr,MSC-1892, Bethesda, MD 20892 USA.
EM rgermain@nih.gov
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX I wish to acknowledge the critical contributions made to the research
and concepts discussed in this review by colleagues and collaborators,
especially I. Stefanova, Gregoire Altan-Bonnet, and Martin
Meier-Schellersheim, as well as J. Madrenas, L. Racioppi, and L.
Samelson. As with any brief review, I apologize to those investigators
whose work could not be cited explicitly due to length and space
constraints. This work was supported by the Intramural Research Program
of the National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 75
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U1 3
U2 12
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0014-5793
J9 FEBS LETT
JI FEBS Lett.
PD DEC 15
PY 2010
VL 584
IS 24
BP 4814
EP 4822
DI 10.1016/j.febslet.2010.10.027
PG 9
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 689QO
UT WOS:000284943600002
PM 20965176
ER
PT J
AU Siraganian, RP
de Castro, RO
Barbu, EA
Zhang, JA
AF Siraganian, Reuben P.
de Castro, Rodrigo O.
Barbu, Emilia A.
Zhang, Juan
TI Mast cell signaling: The role of protein tyrosine kinase Syk, its
activation and screening methods for new pathway participants
SO FEBS LETTERS
LA English
DT Review
DE Mast cell; Fc epsilon RI signal transduction; Syk; Fyn; Gab2;
Phosphatase
ID FC-EPSILON-RI; AFFINITY IGE RECEPTOR; BASOPHILIC LEUKEMIA-CELLS; LOOP
TYROSINES; LINKER REGION; C-CBL; PHOSPHORYLATION; DEGRANULATION;
P72(SYK); TRANSDUCTION
AB The aggregation by antigen of the IgE bound to its high affinity receptor on mast cells initiates a complex series of biochemical events that result in the release of inflammatory mediators. The essential role of the protein tyrosine kinase Syk has been appreciated for some time, and newer results have defined the mechanism of its activation. The use of siRNA has defined the relative contribution of Syk, Fyn and Gab2 to signaling and has made possible a screening study to identify previously unrecognized molecules that are involved in these pathways. Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.
C1 [Siraganian, Reuben P.; de Castro, Rodrigo O.; Barbu, Emilia A.; Zhang, Juan] Natl Inst Dent & Craniofacial Res, Receptors & Signal Transduct Sect, NIH, Bethesda, MD 20892 USA.
RP Siraganian, RP (reprint author), Natl Inst Dent & Craniofacial Res, Receptors & Signal Transduct Sect, NIH, Bldg 49,Rm 1A16, Bethesda, MD 20892 USA.
EM rs53x@nih.gov
FU National Institutes of Health, NIDCR
FX We thank Jacqueline Groves for helpful discussions and review of the
manuscript; we also thank William Swaim for help with morphological
experiments. This work was supported by the Intramural Research Program
of the National Institutes of Health, NIDCR.
NR 50
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U1 0
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0014-5793
J9 FEBS LETT
JI FEBS Lett.
PD DEC 15
PY 2010
VL 584
IS 24
BP 4933
EP 4940
DI 10.1016/j.febslet.2010.08.006
PG 8
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 689QO
UT WOS:000284943600018
PM 20696166
ER
PT J
AU Correa, CR
Li, L
Aldini, G
Carini, M
Chen, CYO
Chun, HK
Cho, SM
Park, KM
Russell, RM
Blumberg, JB
Yeum, KJ
AF Correa, Camila R.
Li, Lei
Aldini, Giancarlo
Carini, Marina
Chen, C. -Y. Oliver
Chun, Hye-Kyung
Cho, Soo-Muk
Park, Ki-Moon
Russell, Robert M.
Blumberg, Jeffrey B.
Yeum, Kyung-Jin
TI Composition and stability of phytochemicals in five varieties of black
soybeans (Glycine max)
SO FOOD CHEMISTRY
LA English
DT Article
DE Glycine max; Variety; Stability; Lutein; Tocopherol; Daidzein; Genistein
ID DENSITY-LIPOPROTEIN OXIDATION; ABSORBENCY CAPACITY ASSAY; ANTIOXIDANT
ACTIVITIES; MASS-SPECTROMETRY; SERUM-LIPIDS; VITAMIN-C; L. MERR.;
SUPPLEMENTATION; ANTHOCYANINS; IDENTIFICATION
AB Phytochemical compositions of five varieties of black soybeans (Glycine max) and their stabilities at room temperature, 4 and -80 degrees C over 14 months were determined by HPLC systems with electrochemical (ECD) and UV detectors. Polyphenol profiling was carried out by a liquid chromatography-electrospray ionisation-mass spectrometry (LC-ESI-MS) with orbitrap as a mass analyser in both positive and negative ion modes, and polyphenols in aglycone forms were quantified by HPLC-ECD. Five different varieties of black soybeans (G. max) contained 249-405 mu g/g dry wt of gamma-tocopherol and 6.76-14.98 mu g/g dry wt of lutein. Major polyphenols in black soybeans (G. max) were daidzein (193-288 mu g/g dry wt) and genistein (145-223 mu g/g dry wt), mainly present as glucosides and acetyl glucosides. No significant decrease was found in total phenols of black soybeans (G. max) stored at room temperature, 4 or -80 degrees C for 14 months. On the other hand, lutein and gamma-tocopherol degraded significantly within a month of storage at room temperature (p < 0.01), whereas they remained stable up to 6 months at 4 C and up to 14 months at -80 degrees C. The current study indicates that black soybeans (G. max) are rich source of gamma-tocopherol and phenols (isoflavones, flavonols, flavan-3-ols, proanthocyanidins and anthocyanin) and that the levels vary depending upon varieties. In addition, storage at low temperature is recommended to reduce the loss of fat-soluble phytochemicals in black soybeans (G. max) over an extended period of time. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Correa, Camila R.; Li, Lei; Chen, C. -Y. Oliver; Blumberg, Jeffrey B.; Yeum, Kyung-Jin] Tufts Univ, Jean Mayer USDA Human Res Ctr Ageing, Boston, MA 02111 USA.
[Li, Lei] Qingdao Univ, Coll Med, Qingdao 266021, Shandong, Peoples R China.
[Aldini, Giancarlo; Carini, Marina] Univ Milan, Dept Pharmaceut Sci Pietro Pratesi, Milan, Italy.
[Chun, Hye-Kyung; Cho, Soo-Muk] Rural Dev Adm, Natl Acad Agr Sci, Seoul, South Korea.
[Park, Ki-Moon] Sungkyunkwan Univ, Dept Food Sci & Biotechnol, Suwon 440746, South Korea.
[Russell, Robert M.] NIH, Off Director, Washington, DC USA.
RP Yeum, KJ (reprint author), Tufts Univ, Jean Mayer USDA Human Res Ctr Ageing, 711 Washington St, Boston, MA 02111 USA.
EM kyungjin.yeum@Tufts.edu
RI CARINI, MARINA/D-3084-2015;
OI CARINI, MARINA/0000-0003-3407-5425; aldini,
giancarlo/0000-0002-2355-6744
FU BioGreen 21 Program [20070301034009]; Rural Development Administration;
Korea and US Department of Agriculture [1950-51000-065-08S]
FX This research has been supported in part by the BioGreen 21 Program
(Code #20070301034009), Rural Development Administration, Korea and US
Department of Agriculture, under Agreement 1950-51000-065-08S. The
contents of this publication do not necessarily reflect the views or
policies of the US Department of Agriculture, nor does mention of trade
names, commercial products, or organizations imply endorsement by the US
Government.
NR 28
TC 18
Z9 18
U1 5
U2 32
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0308-8146
J9 FOOD CHEM
JI Food Chem.
PD DEC 15
PY 2010
VL 123
IS 4
BP 1176
EP 1184
DI 10.1016/j.foodchem.2010.05.083
PG 9
WC Chemistry, Applied; Food Science & Technology; Nutrition & Dietetics
SC Chemistry; Food Science & Technology; Nutrition & Dietetics
GA 639XL
UT WOS:000281010300032
ER
PT J
AU Parkin, DM
Ferlay, J
Curado, MP
Bray, F
Edwards, B
Shin, HR
Forman, D
AF Parkin, D. Max
Ferlay, Jacques
Curado, Maria-Paula
Bray, Freddie
Edwards, Brenda
Shin, Hai-Rim
Forman, David
TI Fifty years of cancer incidence: CI5 I-IX
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE cancer registry; incidence; trend; internet
ID MORTALITY; ADENOCARCINOMA; STATISTICS; CERVIX; TRENDS
AB The Cancer Incidence in Five Continents (CI5) series comprises nine volumes that bring together peer-reviewed results from population-based cancer registries worldwide. The aim of each is to make available comparable data on cancer incidence from as wide a range of geographical locations as possible. In addition, the existence of long time series of data allows the evolution of risk in different populations over time to be studied. The CI5 I-IX database brings together the results from all nine volumes, spanning a period of some 50 years. In addition, unpublished annual data, with more diagnostic detail, are made available for many cancer registries with 15 or more years of recent data. We describe the construction and composition of the CI5 databases, and provide examples of how they can be used to prepare tables and graphs comparing incidence rates between populations. This is the classical role of descriptive statistics: to allow formulation of hypotheses that might explain the observed differences (geographically, over time, in population subgroups) and that can be tested by further study. Such statistics are also essential components in the planning and evaluation of cancer control programmes.
C1 [Parkin, D. Max] Univ Oxford, Clin Trials Serv Unit, Oxford OX3 7LF, England.
[Parkin, D. Max] Univ Oxford, Epidemiol Studies Unit, Oxford OX3 7LF, England.
[Ferlay, Jacques; Curado, Maria-Paula; Bray, Freddie; Shin, Hai-Rim; Forman, David] Int Agcy Res Canc, Canc Informat Sect, F-69372 Lyon, France.
[Edwards, Brenda] NCI, Bethesda, MD 20892 USA.
RP Parkin, DM (reprint author), Univ Oxford, Clin Trials Serv Unit, Richard Doll Bldg,Old Rd Campus, Oxford OX3 7LF, England.
EM max.parkin@ctsu.ox.ac.uk
RI Curado, Maria Paula/M-6200-2013
OI Curado, Maria Paula/0000-0001-8172-2483
NR 32
TC 68
Z9 74
U1 1
U2 9
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 DEC 15
PY 2010
VL 127
IS 12
BP 2918
EP 2927
DI 10.1002/ijc.25517
PG 10
WC Oncology
SC Oncology
GA 680CA
UT WOS:000284208400018
PM 21351270
ER
PT J
AU Sherman, KE
Andersen, JW
Butt, AA
Umbleja, T
Alston, B
Koziel, MJ
Peters, MG
Sulkowski, M
Goodman, ZD
Chung, RT
AF Sherman, Kenneth E.
Andersen, Janet W.
Butt, Adeel A.
Umbleja, Triin
Alston, Beverly
Koziel, Margaret J.
Peters, Marion G.
Sulkowski, Mark
Goodman, Zachary D.
Chung, Raymond T.
CA AIDS Clinical Trials Grp A5178 Stu
TI Sustained Long-Term Antiviral Maintenance Therapy in HCV/HIV-Coinfected
Patients (SLAM-C)
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE fibrosis; HCV; HIV; maintenance; racial disparity
ID CHRONIC HEPATITIS-C; HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-INFECTED
PATIENTS; PROTEASE INHIBITOR THERAPY; ALPHA-2A PLUS RIBAVIRIN;
LIVER-DISEASE; INTERFERON THERAPY; HEPATOCELLULAR-CARCINOMA;
ANTIRETROVIRAL THERAPY; FIBROSIS PROGRESSION
AB Background: Hepatitis C virus (HCV)/HIV coinfection treatment is suboptimal with low sustained viral response rates to standard therapies. A multicenter randomized clinical trial designed to assess the efficacy/safety of pegylated interferon maintenance therapy was performed by the National Institutes of Health-funded AIDS Clinical Trials Group network.
Methods: HCV treatment-naive and nonresponding interferon-experienced subjects with confirmed HCV and HIV, CD4 > 200 cells per cubic millimeter, and at least stage 1 fibrosis were enrolled and treated for 12 weeks with pegylated interferon alfa 2a 180 mcg per week (PEG) + weight-based ribavirin to determine response status. Nonresponder subjects (failure to clear HCV RNA or achieve 2-log drop) underwent liver biopsy and were randomized to receive full dose PEG or observation only for 72 weeks. Paired biopsies were evaluated by a central pathologist.
Results: Three hundred thirty subjects were enrolled; median age was 48 years; 43% white, 37% black, non-Hispanic; 83% male; CD4+ 498 cells per cubic millimeter; 32% were interferon experienced; 74% had entry HIV RNA <50 copies per milliliter. early virologic responder was observed in 55.9% and 42.5% achieved complete Early Viral Response (cEVR). A planned interim analysis of occurred when 84 subjects were randomized. With data on 40 paired biopsies available, a safety monitoring board stopped the trial due to lack of fibrosis progression (median = 0 Metavir units/year) in the observation arm.
Conclusions: Lack of fibrotic progression in the control arm was unexpected and may represent a short-term PEG/ribavirin therapy effect, high levels of HIV viral suppression, and use of antiretroviral regimens that may be less toxic than prior generations of therapy.
C1 [Sherman, Kenneth E.] Univ Cincinnati, Coll Med, Div Digest Dis, Dept Internal Med, Cincinnati, OH 45267 USA.
[Andersen, Janet W.; Umbleja, Triin] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA.
[Butt, Adeel A.] Univ Pittsburgh, Div Infect Dis, Pittsburgh, PA USA.
[Alston, Beverly] NIAID, Div Aids, Bethesda, MD 20892 USA.
[Koziel, Margaret J.] Beth Israel Deaconess Med Ctr, Harvard Inst Med, Boston, MA 02215 USA.
[Peters, Marion G.] Univ Calif San Francisco, Dept Gastroenterol, San Francisco, CA 94143 USA.
[Sulkowski, Mark] Johns Hopkins Univ, Div Infect Dis & Gastroenterol Hepatol, Baltimore, MD USA.
[Goodman, Zachary D.] Armed Forces Inst Pathol, Washington, DC 20306 USA.
[Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA.
RP Sherman, KE (reprint author), Univ Cincinnati, Coll Med, Div Digest Dis, Dept Internal Med, 231 Albert Sabin Way, Cincinnati, OH 45267 USA.
EM kenneth.sherman@uc.edu
FU National Institute of Allergy and Infectious Diseases [U01 AI068634, U01
AI38858, U01 AI068636]; NIDDK [K24 DK070528, RO1 16065]; National Center
for Research Resources; Roche Pharmaceuticals
FX The project described was supported by National Institute of Allergy and
Infectious Diseases funding to the AIDS Clinical Trials Group including
U01 AI068634, U01 AI38858, U01 AI068636, an NIDDK K24 DK070528 to
K.E.S., and an RO1 16065 to M.S. Also supported in part by the General
Clinical Research Center Units funded by the National Center for
Research Resources. Study drug and other support was provided by Roche
Pharmaceuticals. Statistical analysis of the entire data sets pertaining
to efficacy and safety have been independently confirmed by a
biostatistician who is not employed by the corporate entity.
NR 32
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U1 0
U2 1
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 DEC 15
PY 2010
VL 55
IS 5
BP 597
EP 605
DI 10.1097/QAI.0b013e3181f6d916
PG 9
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 679FR
UT WOS:000284147500011
PM 20921898
ER
PT J
AU Hodder, SL
Justman, J
Haley, DE
Adimora, AA
Fogel, CI
Golin, CE
O'Leary, A
Soto-Torres, L
Wingood, G
El-Sadr, WM
AF Hodder, Sally L.
Justman, Jessica
Haley, Danielle E.
Adimora, Adaora A.
Fogel, Catherine I.
Golin, Carol E.
O'Leary, Ann
Soto-Torres, Lydia
Wingood, Gina
El-Sadr, Wafaa M.
CA Hiv Prevention Trials Network Dome
TI Challenges of a Hidden Epidemic: HIV Prevention Among Women in the
United States
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE HIV in women; HIV prevention science; racial disparity
ID SEXUALLY-TRANSMITTED-DISEASE; AFRICAN-AMERICAN WOMEN; RANDOMIZED
CONTROLLED-TRIAL; BEHAVIORAL INTERVENTIONS; CONCURRENT PARTNERSHIPS;
RACIAL DISPARITIES; INFECTIOUS-DISEASE; SOCIAL-CONTEXT; RISK BEHAVIOR;
DOUBLE-BLIND
AB HIV/AIDS trends in the United States depict a concentrated epidemic with hot spots that vary by location, poverty, race/ethnicity, and transmission mode. HIV/AIDS is a leading cause of death among US women of color; two-thirds of new infections among women occur in black women, despite the fact that black women account for just 14% of the US female population. The gravity of the HIV epidemic among US women is often not appreciated by those at risk and by the broader scientific community. We summarize the current epidemiology of HIV/AIDS among US women and discuss clinical, research, and public health intervention components that must be brought together in a cohesive plan to reduce new HIV infections in US women. Only by accelerating research and programmatic efforts will the hidden epidemic of HIV among US women emerge into the light and come under control.
C1 [Hodder, Sally L.] Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07101 USA.
[Justman, Jessica; El-Sadr, Wafaa M.] Columbia Univ, Int Ctr AIDS Care & Treatment Programs, Mailman Sch Publ Hlth, New York, NY USA.
[Justman, Jessica; El-Sadr, Wafaa M.] Columbia Univ, Coll Phys & Surg, New York, NY USA.
[Haley, Danielle E.] FHI, Durham, NC USA.
[Adimora, Adaora A.] Univ N Carolina, Sch Med, Chapel Hill, NC USA.
[Fogel, Catherine I.] Univ N Carolina, Sch Nursing, Chapel Hill, NC USA.
[Golin, Carol E.] Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA.
[O'Leary, Ann] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Soto-Torres, Lydia] NIH, Div Aids, Bethesda, MD 20892 USA.
[Wingood, Gina] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.
[El-Sadr, Wafaa M.] Harlem Hosp Med Ctr, New York, NY USA.
RP Hodder, SL (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, 185 S Orange Ave,MSB I-510, Newark, NJ 07101 USA.
EM hoddersa@umdnj.edu
FU HIV Prevention Trials Network (HPTN); National Institute of Allergy and
Infectious Disease and the National Institute of Mental Health, both in
Bethesda, MD [U01 AIO68619, U01 AI068619]; National Institute of Allergy
and Infectious Disease and the National Institute of Mental Health [U01
AIO68619, U01 AI068619, U01 AI069466-0351, U01 AI069466, AI06819, U01
AIO69423, U01 AI069423]; Emory Center for AIDS Research, Atlanta, GA
[P30 AI050409]
FX This project was supported by the HIV Prevention Trials Network and
sponsored by the National Institute of Allergy and Infectious Disease
and the National Institute of Mental Health, both in Bethesda, MD, under
award number U01 AIO68619. The authors' work on this article was
supported in part by grants from National Institute of Allergy and
Infectious Disease and the National Institute of Mental Health, under
award numbers U01 AI069466-0351 (Dr S.L.H.), U01 AI069466 (Dr W.M.E. and
Dr J.J.), AI06819 (Dr J.J.), U01 AIO68619 (Ms D.F.H.), and U01 AIO69423
(Dr A.A.A., Dr C.I.F., and Dr C.E.G.); and the Emory Center for AIDS
Research, Atlanta, GA, under award number P30 AI050409 (Dr G.W.).; The
authors wish to acknowledge the contributions of Drs. Sten Vermund,
Quarraisha Abdool-Karim, David Metzger; Nirupama Sista and Ms. Harmony
Waller This project was supported by the HIV Prevention Trials Network
(HPTN) and sponsored by the National Institute of Allergy and Infectious
Diseases (MAID) in Bethesda, MD, under award number U01 AI068619. The
authors' work on this manuscript was supported in part by grants from
NIAID and NIMH, under award numbers U01 AI069466 (Dr Hodder), U01
AI069466 (Dr El-Sadr and Dr Justman), AI06819 (Dr Justman), U01 AI068619
(Ms Haley), and U01 AI069423 (Dr Adimora, Dr Fogel, and Dr Golin); and
the Emory Center for AIDS Research, Atlanta, GA, under award number P30
AI050409 (Dr Wingood). The views expressed herein are solely the
responsibility of the authors and do not necessarily represent the
official views of NIAID, NIH, the HPTN, the Centers for Disease Control
and Prevention, or its funders.
NR 66
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U1 4
U2 12
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 DEC 15
PY 2010
VL 55
SU 2
BP S69
EP S73
DI 10.1097/QAI.0b013e3181fbbdf9
PG 5
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 689YD
UT WOS:000284966100003
PM 21406990
ER
PT J
AU Millett, GA
Crowley, JS
Koh, H
Valdiserri, RO
Frieden, T
Dieffenbach, CW
Fenton, KA
Benjamin, R
Whitescarver, J
Mermin, J
Parham-Hopson, D
Fauci, AS
AF Millett, Gregorio A.
Crowley, Jeffrey S.
Koh, Howard
Valdiserri, Ronald O.
Frieden, Thomas
Dieffenbach, Carl W.
Fenton, Kevin A.
Benjamin, Regina
Whitescarver, Jack
Mermin, Jonathan
Parham-Hopson, Deborah
Fauci, Anthony S.
TI A Way Forward: The National HIV/AIDS Strategy and Reducing HIV Incidence
in the United States
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE HIV/AIDS; National; Obama; President; strategy
ID ANTIRETROVIRAL THERAPY; SEXUAL TRANSMISSION; INFECTION; METAANALYSIS;
DISPARITIES; PREVENTION; BEHAVIOR; HEALTH; CARE
AB In July 2010, the Obama Administration released a National HIV/AIDS Strategy for the United States to refocus national attention on responding to the domestic HIV epidemic. The goals of the strategy are to reduce HIV incidence; to increase access to care and optimize health outcomes among people living with HIV; and to reduce HIV-related disparities. The strategy identifies a small number of action steps that will align efforts across federal, state, local, and tribal levels of government, and maximally impact the domestic HIV epidemic. In this article, we outline key programmatic and research issues that must be addressed to accomplish the prevention goals of the National HIV/AIDS Strategy.
C1 [Millett, Gregorio A.; Crowley, Jeffrey S.] White House, Off Natl AIDS Policy, Washington, DC 20502 USA.
[Frieden, Thomas] Off Director, Ctr Dis Control & Prevent, Atlanta, GA USA.
[Koh, Howard; Valdiserri, Ronald O.] Off Publ Hlth & Sci, Dept Hlth & Human Serv, Rockville, MD USA.
[Dieffenbach, Carl W.] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA.
[Fenton, Kevin A.; Mermin, Jonathan] Ctr Dis Control & Prevent, Natl Ctr HIV AIDS Viral Hepatitis STD & TB Preven, Atlanta, GA USA.
[Benjamin, Regina] Off Surg Gen, Dept Hlth & Human Serv, Rockville, MD USA.
[Whitescarver, Jack] Off AIDS Res, Off Director, NIH, Bethesda, MD USA.
[Parham-Hopson, Deborah] NIAID, HIV AIDS Bur, Hlth Resources & Serv Adm, NIH, Bethesda, MD 20892 USA.
[Fauci, Anthony S.] NIAID, Off Director, NIH, Bethesda, MD 20892 USA.
RP Millett, GA (reprint author), White House, Off Natl AIDS Policy, Washington, DC 20502 USA.
EM gmillett@who.eop.gov
RI Mermin, Jonathan/J-9847-2012
NR 25
TC 38
Z9 38
U1 3
U2 12
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 DEC 15
PY 2010
VL 55
SU 2
BP S144
EP S147
DI 10.1097/QAI.0b013e3181fbcb04
PG 4
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 689YD
UT WOS:000284966100019
PM 21406986
ER
PT J
AU Grady, C
AF Grady, Christine
TI Institutional Review Boards and Protecting Human Research Participants
Reply
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Letter
C1 NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
RP Grady, C (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
EM cgrady@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD DEC 15
PY 2010
VL 304
IS 23
BP 2592
EP 2592
DI 10.1001/jama.2010.1823
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 694MX
UT WOS:000285303400020
ER
PT J
AU Song, M
Zhang, SY
Xu, XY
Hang, TJ
Jia, L
AF Song, Min
Zhang, Siyun
Xu, Xiaoyan
Hang, Taijun
Jia, Lee
TI Simultaneous determination of three Panax notoginseng saponins at
sub-nanograms by LC-MS/MS in dog plasma for pharmacokinetics of compound
Danshen tablets
SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL
AND LIFE SCIENCES
LA English
DT Article
DE Compound Danshen tablets; notoginsenoside R1; ginsenoside Rg1;
ginsenoside Rb1; LC-MS/MS; Pharmacokinetics
ID PERFORMANCE LIQUID-CHROMATOGRAPHY; TANDEM MASS-SPECTROMETRY; SOLID-PHASE
EXTRACTION; 4 ACTIVE SAPONINS; RAT PLASMA; GINSENOSIDE RB-1; SHENMAI
INJECTION; INTESTINAL BACTERIA; RB1; RG(1)
AB Compound Danshen tablets are composed of Panax notoginseng, Salvia miltiorrhiza and Borneol. The tablets are prescribed for treatment of cardiovascular diseases in China. The present study aimed at developing a specific and sensitive LC-MS/MS method to simultaneously determine three bioactive P. notoginseng saponins, i.e., notoginsenoside R1. ginsenoside Rg1 and Rb1, in dogs after a single oral administration of the compound tablets in order to obtain the clinically relevant saponin-related pharmacodynamics of the tablets in patients. The R1, Rg1 and Rb1 were extracted from dog plasma with acetone-methanol (80:20, v/v), separated by reversed phase liquid chromatography and determined by tandem mass spectrometry (LC-MS/MS) with positive electrospray ionization (ESI). The developed method reached lower limit of quantitation (LLOQ) at 0.10 ng/ml for the three saponins. The method was validated in terms of selectivity, matrix effects, linearity, precision and accuracy, and then was applied to a pharmacokinetic study of the three bioactive saponins simultaneously in dogs after a single oral administration of compound Danshen tablets at a clinical equivalent dose. The C(max) and AUC((o-infinity)) for R1, Rg1 and Rb1 were 1.91, 3.34 and 28.6 ng/ml, and 7.5, 11.0, and 1712 (h ng/ml), respectively. (c) 2010 Elsevier ay. All rights reserved.
C1 [Song, Min; Zhang, Siyun; Xu, Xiaoyan; Hang, Taijun] China Pharmaceut Univ, Dept Pharmaceut Anal, Nanjing 210009, Peoples R China.
[Jia, Lee] NCI, Dev Therapeut Program, NIH, Rockville, MD 20852 USA.
RP Song, M (reprint author), China Pharmaceut Univ, Dept Pharmaceut Anal, Nanjing 210009, Peoples R China.
EM cqsongmin@yahoo.cn; zhangsiyun1984@hotmail.com;
xiaoyan202003@yahoo.com.cn; hangtj@cpu.edu.cn; jiale@mail.nih.gov
FU Ministry of Education of China [20090096120004]; China Postdoctoral
Science Foundation [20070411039]; China Pharmaceutical University
FX This research was supported by Doctoral Fund of Ministry of Education of
China (20090096120004), China Postdoctoral Science Foundation
(20070411039) and by special fund of China Pharmaceutical University.
NR 46
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Z9 23
U1 9
U2 51
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1570-0232
J9 J CHROMATOGR B
JI J. Chromatogr. B
PD DEC 15
PY 2010
VL 878
IS 32
BP 3331
EP 3337
DI 10.1016/j.jchromb.2010.10.007
PG 7
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 703CK
UT WOS:000285951500001
PM 21081293
ER
PT J
AU Thornton, AM
Shevach, EM
AF Thornton, Angela M.
Shevach, Ethan M.
TI Response to Comment on "Expression of Helios, an Ikaros Transcription
Factor Family Member, Differentiates Thymic-Derived from Peripherally
Induced Foxp3(+) T Regulatory Cells"
SO JOURNAL OF IMMUNOLOGY
LA English
DT Letter
C1 [Shevach, Ethan M.] NIAID, Cellular Immunol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Shevach, EM (reprint author), NIAID, Cellular Immunol Sect, Immunol Lab, NIH, Bldg 10,Room 11N315, Bethesda, MD 20892 USA.
EM eshevach@niaid.nih.gov
NR 1
TC 1
Z9 1
U1 0
U2 2
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD DEC 15
PY 2010
VL 185
IS 12
BP 7129
EP 7130
DI 10.4049/jimmunol.1090106
PG 2
WC Immunology
SC Immunology
GA 688UF
UT WOS:000284878700002
ER
PT J
AU Kinjyo, I
Gordon, SM
Intlekofer, AM
Dowdell, K
Mooney, EC
Caricchio, R
Grupp, SA
Teachey, DT
Rao, VK
Lindsten, T
Reiner, SL
AF Kinjyo, Ichiko
Gordon, Scott M.
Intlekofer, Andrew M.
Dowdell, Kennichi
Mooney, Erin C.
Caricchio, Roberto
Grupp, Stephan A.
Teachey, David T.
Rao, V. Koneti
Lindsten, Tullia
Reiner, Steven L.
TI Cutting Edge: Lymphoproliferation Caused by Fas Deficiency Is Dependent
on the Transcription Factor Eomesodermin
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID CD8(+) T-CELLS; MICE; BET; HOMEOSTASIS; ELIMINATION; EFFECTOR
AB A hallmark of autoimmune lymphoproliferative syndrome (ALPS), caused by mutation of the Fas death receptor, is massive lymphadenopathy from aberrant expansion of CD4(-)CD8(-) (double-negative [DN]) T cells. Eomesodermin (Eomes) is a member of the T-box family of transcription factors and plays critical roles in effector cell function and memory cell fitness of CD8(+) T lymphocytes. We provide evidence in this study that DN T cells exhibit dysregulated expression of Eomes in humans and mice with ALPS. We also find that T cell-specific deletion of Eomes prevents lymphoid hypertrophy and accumulation of DN T cells in Fas-mutant mice. Although Eomes has critical physiological roles in the function and homeostasis of CD8(+) T cells, overexpression of Eomes appears to enable pathological induction or expansion of unusual CD8-related T cell subsets. Thus, antagonism of Eomes emerges as a therapeutic target for DN T cell ablation in ALPS. The Journal of Immunology, 2010, 185: 7151-7155.
C1 [Kinjyo, Ichiko; Gordon, Scott M.; Intlekofer, Andrew M.; Mooney, Erin C.; Lindsten, Tullia; Reiner, Steven L.] Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA.
[Kinjyo, Ichiko; Gordon, Scott M.; Intlekofer, Andrew M.; Mooney, Erin C.; Reiner, Steven L.] Univ Penn, Div Infect Dis, Dept Med, Philadelphia, PA 19104 USA.
[Grupp, Stephan A.; Teachey, David T.] Univ Penn, Dept Pediat, Philadelphia, PA 19104 USA.
[Lindsten, Tullia] Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA.
[Dowdell, Kennichi; Rao, V. Koneti] NIAID, NIH, Bethesda, MD 20892 USA.
[Caricchio, Roberto] Temple Univ, Div Rheumatol, Dept Med, Philadelphia, PA 19122 USA.
[Grupp, Stephan A.; Teachey, David T.] Childrens Hosp, Dept Pediat, Philadelphia, PA 19104 USA.
RP Reiner, SL (reprint author), Univ Penn, Abramson Family Canc Res Inst, 421 Curie Blvd,BRB 2-3,Room 414, Philadelphia, PA 19104 USA.
EM sreiner@mail.med.upenn.edu
FU National Institutes of Health [AI042370, AI076458, AI061699]; Abramson
Family; Training Grant [T32 CA09140]; National Institutes of Health,
National Institute of Allergy and Infectious Diseases, Bethesda, MD
FX This work was supported by National Institutes of Health Grants
AI042370, AI076458, and AI061699, the Abramson Family (to S. L. R.), and
Training Grant T32 CA09140 (to S. M. G.). Part of this work was also
supported by the Intramural Research Program of the National Institutes
of Health, National Institute of Allergy and Infectious Diseases,
Bethesda, MD.
NR 24
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U1 0
U2 1
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD DEC 15
PY 2010
VL 185
IS 12
BP 7151
EP 7155
DI 10.4049/jimmunol.1003193
PG 5
WC Immunology
SC Immunology
GA 688UF
UT WOS:000284878700008
PM 21076068
ER
PT J
AU Kannanganat, S
Nigam, P
Velu, V
Earl, PL
Lai, LL
Chennareddi, L
Lawson, B
Wilson, RL
Montefiori, DC
Kozlowski, PA
Moss, B
Robinson, HL
Amara, RR
AF Kannanganat, Sunil
Nigam, Pragati
Velu, Vijayakumar
Earl, Patricia L.
Lai, Lilin
Chennareddi, Lakshmi
Lawson, Benton
Wilson, Robert L.
Montefiori, David C.
Kozlowski, Pamela A.
Moss, Bernard
Robinson, Harriet L.
Amara, Rama Rao
TI Preexisting Vaccinia Virus Immunity Decreases SIV-Specific Cellular
Immunity but Does Not Diminish Humoral Immunity and Efficacy of a
DNA/MVA Vaccine
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID SIMIAN IMMUNODEFICIENCY VIRUS; CD4(+) T-CELLS; GM-CSF DNA; NEUTRALIZING
ANTIBODIES; ADENOVIRUS VECTORS; GAG-POL; ENVELOPE GLYCOPROTEIN; MUCOSAL
CHALLENGE; 89.6P CHALLENGE; RHESUS MACAQUES
AB The influence of preexisting immunity to viral vectors is a major issue for the development of viral-vectored vaccines. In this study, we investigate the effect of preexisting vaccinia virus immunity on the immunogenicity and efficacy of a DNA/modified vaccinia Ankara (MVA) SIV vaccine in rhesus macaques using a pathogenic intrarectal SIV251 challenge. Preexisting immunity decreased SIV-specific CD8 and CD4 T cell responses but preserved the SIV-specific humoral immunity. In addition, preexisting immunity did not diminish the control of an SIV challenge mediated by the DNA/MVA vaccine. The peak and set point viremia was 150- and 17-fold lower, respectively, in preimmune animals compared with those of control animals. The peak and set point viremia correlated directly with colorectal virus at 2 wk postchallenge suggesting that early control of virus replication at the site of viral challenge was critical for viral control. Factors that correlated with early colorectal viral control included 1) the presence of anti-SIV IgA in rectal secretions, 2) high-avidity binding Ab for the native form of Env, and 3) low magnitude of vaccine-elicited SIV-specific CD4 T cells displaying the CCR5 viral coreceptor. The frequency of SIV-specific CD8 T cells in blood and colorectal tissue at 2 wk postchallenge did not correlate with early colorectal viral control. These results suggest that preexisting vaccinia virus immunity may not limit the potential of recombinant MVA vaccines to elicit humoral immunity and highlight the importance of immunodeficiency virus vaccines achieving early control at the mucosal sites of challenge. The Journal of Immunology, 2010, 185: 7262-7273.
C1 [Kannanganat, Sunil; Nigam, Pragati; Velu, Vijayakumar; Lai, Lilin; Chennareddi, Lakshmi; Lawson, Benton; Robinson, Harriet L.; Amara, Rama Rao] Emory Univ, Dept Microbiol & Immunol, Vaccine Res Ctr, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA.
[Earl, Patricia L.; Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
[Wilson, Robert L.; Kozlowski, Pamela A.] Louisiana State Univ, Hlth Sci Ctr, Gene Therapy Program, Dept Microbiol Immunol & Parasitol, New Orleans, LA 70112 USA.
[Montefiori, David C.] Duke Univ, Med Ctr, Lab AIDS Vaccine Res & Dev, Dept Surg, Durham, NC 27710 USA.
RP Amara, RR (reprint author), 954 Gatewood Rd, Atlanta, GA 30329 USA.
EM ramara@emory.edu
OI Velu, Vijayakumar/0000-0003-4238-1924
FU National Institute of Allergy and Infectious Diseases/National
Institutes of Health [R01 AI057029, R01 AI071852]; Yerkes National
Primate Research Center [P51 RR00165]; Emory Centers for AIDS [P30
AI050409]; National Institutes of Health [R24 RR16038]
FX This work was supported by National Institute of Allergy and Infectious
Diseases/National Institutes of Health Grants R01 AI057029 and R01
AI071852 (to R.R.A.), Yerkes National Primate Research Center Base Grant
P51 RR00165, Emory Centers for AIDS Research Grant P30 AI050409, and
National Institutes of Health Grant R24 RR16038 (to David I. Watkins).
NR 60
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Z9 15
U1 0
U2 1
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD DEC 15
PY 2010
VL 185
IS 12
BP 7262
EP 7273
DI 10.4049/jimmunol.1000751
PG 12
WC Immunology
SC Immunology
GA 688UF
UT WOS:000284878700022
PM 21076059
ER
PT J
AU Chinn, LW
Tang, MZ
Kessing, BD
Lautenberger, JA
Troyer, JL
Malasky, MJ
McIntosh, C
Kirk, GD
Wolinsky, SM
Buchbinder, SP
Gomperts, ED
Goedert, JJ
O'Brien, SJ
AF Chinn, Leslie W.
Tang, Minzhong
Kessing, Bailey D.
Lautenberger, James A.
Troyer, Jennifer L.
Malasky, Michael J.
McIntosh, Carl
Kirk, Gregory D.
Wolinsky, Steven M.
Buchbinder, Susan P.
Gomperts, Edward D.
Goedert, James J.
O'Brien, Stephen J.
TI Genetic Associations of Variants in Genes Encoding HIV-Dependency
Factors Required for HIV-1 Infection
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; GENOME-WIDE ASSOCIATION; INTERACTION
DATABASE; PROTEIN; AIDS; REPLICATION; COMPLEX; IDENTIFICATION;
RESTRICTION; PROGRESSION
AB Background. High-throughput genome-wide techniques have facilitated the identification of previously unknown host proteins involved in cellular human immunodeficiency virus (HIV) infection. Recently, 3 independent studies have used small interfering RNA technology to silence each gene in the human genome to determine the importance of each in HIV infection. Genes conferring a significant effect were termed HIV-dependency factors (HDFs).
Methods. We assembled high-density panels of 6380 single-nucleotide polymorphisms (SNPs) in 278 HDF genes and tested for genotype associations with HIV infection and AIDS progression in 1633 individuals from clinical AIDS cohorts.
Results. After statistical correction for multiple tests, significant associations with HIV acquisition were found for SNPs in 2 genes, NCOR2 and IDH1. Weaker associations with AIDS progression were revealed for SNPs within the TM9SF2 and EGFR genes.
Conclusions. This study independently verifies the influence of NCOR2 and IDH1 on HIV transmission, and its findings suggest that variation in these genes affects susceptibility to HIV infection in exposed individuals.
C1 [Gomperts, Edward D.] Univ So Calif, Los Angeles, CA USA.
[Gomperts, Edward D.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA.
[Buchbinder, Susan P.] San Francisco Dept Publ Hlth, San Francisco, CA USA.
[Wolinsky, Steven M.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Kirk, Gregory D.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Goedert, James J.] NCI, Rockville, MD USA.
[Kessing, Bailey D.; Troyer, Jennifer L.; Malasky, Michael J.] Sci Applicat Int Corp, Frederick, MD USA.
[O'Brien, Stephen J.] NCI, Lab Genom Divers, Frederick, MD 21702 USA.
RP O'Brien, SJ (reprint author), NCI, Lab Genom Divers, Frederick, MD 21702 USA.
EM stephen.obrien@nih.gov
RI Wolinsky, Steven/B-2893-2012; Troyer, Jennifer/B-8415-2012;
OI Wolinsky, Steven/0000-0002-9625-6697
FU National Cancer Institute (NCI), National Institutes of Health (NIH)
[HHSN261200800001E, N01-CO-12400]; NIH [R01-DA-04334, R01-DA-12568,
UO1-AI-35042, 5-MO1-RR-00722, UO1-AI-35043, UO1-AI-37984, UO1-AI-35039,
UO1-AI-35040, UO1-AI-37613, UO1-AI-35041, M01 RR00425]; NCI
[UO1-AI-35042, 5-MO1-RR-00722, UO1-AI-35043, UO1-AI-37984, UO1-AI-35039,
UO1-AI-35040, UO1-AI-37613, UO1-AI-35041, N02-CP-55504]; NIH, National
Institute of Child Health and Human Development [1 R01 HD41224]
FX Financial support: This project has been funded in whole or in part with
federal funds from the National Cancer Institute (NCI), National
Institutes of Health (NIH; contract HHSN261200800001E). AIDS Link to the
Intravenous Experience was supported by NIH grants R01-DA-04334 and
R01-DA-12568. Multicenter AIDS Cohort Study work was supported by NIH
grants UO1-AI-35042, 5-MO1-RR-00722 (GCRC), UO1-AI-35043, UO1-AI-37984,
UO1-AI-35039, UO1-AI-35040, UO1-AI-37613, UO1-AI-35041, and M01 RR00425
(National Center for Research Resources grant awarded to the GCRC at
Harbor-University of California, Los Angeles, Research and Education
Institute). The Multicenter Hemophilia Cohort Study is supported by NCI
contract N02-CP-55504 with RTI International. The Hemophilia Growth and
Development Study is funded by the NIH, National Institute of Child
Health and Human Development, grant 1 R01 HD41224. NCI contracts include
the following: UO1-AI-35042, 5-MO1-RR-00722 (GCRC), UO1-AI-35043,
UO1-AI-37984, UO1-AI-35039, UO1-AI-35040, UO1-AI-37613, and
UO1-AI-35041. This project has been funded in whole or in part with
federal funds from the NCI, NIH, under contract N01-CO-12400. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 38
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Z9 11
U1 1
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD DEC 15
PY 2010
VL 202
IS 12
BP 1836
EP 1845
DI 10.1086/657322
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 681XC
UT WOS:000284356300011
PM 21083371
ER
PT J
AU Li, M
Cheung, GYC
Hu, JH
Wang, DC
Joo, HS
DeLeo, FR
Otto, M
AF Li, Min
Cheung, Gordon Y. C.
Hu, Jinhui
Wang, Decheng
Joo, Hwang-Soo
DeLeo, Frank R.
Otto, Michael
TI Comparative Analysis of Virulence and Toxin Expression of Global
Community-Associated Methicillin-Resistant Staphylococcus aureus Strains
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID PANTON-VALENTINE LEUKOCIDIN; GENE-EXPRESSION; POLYMORPHONUCLEAR
LEUKOCYTES; SKIN INFECTIONS; PNEUMONIA; EVOLUTION; DISEASE; USA300;
MRSA; AGR
AB The current pandemic of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) skin infections is caused by several genetically unrelated clones. Here, we analyzed virulence of globally occurring CA-MRSA strains in a rabbit skin infection model. We used rabbits because neutrophils from this animal species have relatively high sensitivity to Panton-Valentine leukocidin (PVL), a toxin epidemiologically correlated with many CA-MRSA infections. Virulence in the rabbit model correlated with in vitro neutrophil lysis and transcript levels of phenol-soluble modulin a and a-toxin, but not PVL genes. Furthermore, abscesses caused by USA300 and its PVL-negative progenitor USA500 were comparatively large and similar in size, suggesting that PVL has played a limited role in the evolution of USA300 virulence in the context of skin infections. Our study indicates a major but not exclusive impact of virulence on the epidemiological success of USA300 and other CA-MRSA strains and emphasizes the importance of core genome-encoded toxins in CA-MRSA skin infections.
C1 [Otto, Michael] NIAID, Lab Human Bacterial Pathogenesis, NIH, Bethesda, MD 20892 USA.
[Li, Min; Hu, Jinhui] Huashan Hosp, Dept Lab Med, Shanghai 200040, Peoples R China.
[Wang, Decheng; Joo, Hwang-Soo] Fudan Univ, Shanghai Med Coll, Key Lab Med Mol Virol, Inst Med Microbiol, Shanghai 200433, Peoples R China.
[Wang, Decheng; Joo, Hwang-Soo] Fudan Univ, Shanghai Med Coll, Inst Biomed Sci, Shanghai 200433, Peoples R China.
[DeLeo, Frank R.] NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
RP Otto, M (reprint author), NIAID, Lab Human Bacterial Pathogenesis, NIH, Bldg 33,1W10,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM ruth_limin124@yahoo.com; motto@niaid.nih.gov
RI Cheung, Yiu Chong /K-3565-2012;
OI JOO, HWANG-SOO/0000-0003-4668-3225; DeLeo, Frank/0000-0003-3150-2516;
Otto, Michael/0000-0002-2222-4115
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health; National Natural Science Foundation of China;
Shanghai Pujiang Program [09PJ1402300]
FX Financial support: This work was supported by the Intramural Research
Program of the National Institute of Allergy and Infectious Diseases,
National Institutes of Health (to M.O. and F. R. D.), the National
Natural Science Foundation of China (grant 30900026 to M. L.), and the
Shanghai Pujiang Program (grant 09PJ1402300 to M.L.).
NR 44
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Z9 100
U1 1
U2 11
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD DEC 15
PY 2010
VL 202
IS 12
BP 1866
EP 1876
DI 10.1086/657419
PG 11
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 681XC
UT WOS:000284356300014
PM 21050125
ER
PT J
AU Sweeney, DA
Cui, XZ
Solomon, SB
Vitberg, DA
Migone, TS
Scher, D
Danner, RL
Natanson, C
Subramanian, GM
Eichacker, PQ
AF Sweeney, Daniel A.
Cui, Xizhong
Solomon, Steven B.
Vitberg, David A.
Migone, Thi S.
Scher, Dara
Danner, Robert L.
Natanson, Charles
Subramanian, G. Mani
Eichacker, Peter Q.
TI Anthrax Lethal and Edema Toxins Produce Different Patterns of
Cardiovascular and Renal Dysfunction and Synergistically Decrease
Survival in Canines
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID BACILLUS-ANTHRACIS; CYCLIC-AMP; ESCHERICHIA-COLI; INHALATIONAL ANTHRAX;
PROTECTIVE ANTIGEN; CHOLERA TOXIN; SEPTIC SHOCK; DOWN METHOD; RAT MODEL;
IN-VIVO
AB Background. High mortality in the 2001 US and recent European anthrax outbreaks suggests that better understanding of the effects of the toxins produced by this bacterium is needed to improve treatment.
Methods and results. Here, 24-h edema (ETx) and lethal (LeTx) toxin infusions were investigated for 96 h in sedated canines receiving mechanical ventilation. The initial study compared similarly lethal doses of ETx (n = 8) or LeTx (n = 15) alone. ETx was 24 times less lethal than LeTx, and the median time to death in nonsurvivors (n = 6 and n = 9, respectively) was shorter with ETx (42 vs 67 h; P = .04). Compared with controls (n = 9), both toxins decreased arterial and central venous pressures and systemic vascular resistance and increased heart rate, cardiac index, blood urea nitrogen (BUN) level, creatinine (Cr) concentration, BUN: Cr ratio, and hepatic transaminase levels (P <= .05 for toxin effect or time interaction). However, ETx stimulated early diuresis, reduced serum sodium levels, and had more pronounced vasodilatory effects, compared with LeTx, as reflected by greater or earlier central venous pressures, systemic vascular resistance, and changes in the BUN: Cr ratio (P <= .01). LeTx progressively decreased the left ventricular ejection fraction (P <= .002). In a subsequent study, a lethal dose of LeTx with an equimolar nonlethal ETx dose (n = 8) increased mortality, compared with LeTx alone (n = 8; P = .05).
Conclusion. Shock with ETx or LeTx may require differing supportive therapies, whereas toxin antagonists should likely target both toxins.
C1 [Sweeney, Daniel A.; Cui, Xizhong; Solomon, Steven B.; Vitberg, David A.; Scher, Dara; Danner, Robert L.; Natanson, Charles; Eichacker, Peter Q.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
[Migone, Thi S.; Subramanian, G. Mani] Human Genome Sci, Rockville, MD USA.
RP Eichacker, PQ (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bldg 10,Rm 2C145, Bethesda, MD 20892 USA.
EM peichacker@mail.cc.nih.gov
FU National Institutes of Health (NIH) Clinical Center; Trans NIH-Food and
Drug Administration Biodefense
FX Financial support: National Institutes of Health (NIH) Clinical Center;
Trans NIH-Food and Drug Administration Biodefense grant.
NR 46
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U1 0
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD DEC 15
PY 2010
VL 202
IS 12
BP 1885
EP 1896
DI 10.1086/657408
PG 12
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 681XC
UT WOS:000284356300016
PM 21067373
ER
PT J
AU Brotman, RM
Klebanoff, MA
Nansel, TR
Yu, KF
Andrews, WW
Zhang, J
Schwebke, JR
AF Brotman, Rebecca M.
Klebanoff, Mark A.
Nansel, Tonja R.
Yu, Kai F.
Andrews, William W.
Zhang, Jun
Schwebke, Jane R.
TI Bacterial Vaginosis Assessed by Gram Stain and Diminished Colonization
Resistance to Incident Gonococcal, Chlamydial, and Trichomonal Genital
Infection
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID SEXUALLY-TRANSMITTED-DISEASES; IMMUNODEFICIENCY-VIRUS TYPE-1; REPORTED
CONDOM USE; VAGINAL FLORA; TRACT-INFECTIONS; IN-VITRO; WOMEN;
ASSOCIATION; ACQUISITION; HIV
AB Background. We sought to assess the relationship between bacterial vaginosis (BV) assessed by Gram stain and incident trichomonal, gonococcal, and/or chlamydial genital infection.
Methods. This longitudinal study included 3620 nonpregnant women aged 15-44 years who presented for routine care at 12 clinics in Birmingham, Alabama. Participants were assessed quarterly for 1 year. Vaginal smears were categorized by the Nugent Gram stain score (0 3, normal; 4 6, intermediate state; 7 10, BV). Pooled logistic regression was used to estimate the hazard ratios for the comparison of trichomonal, gonococcal, and chlamydial infection incidence in participants by Nugent score at the prior visit. Participants were censored at their first visit with a positive test result for trichomonal, gonococcal, and/or chlamydial infection.
Results. Of the 10,606 eligible visits, 37.96% were classified by BV and 13.3% by positive detection of trichomonal, gonococcal, and/or chlamydial infection. An intermediate state or BV at the prior visit was associated with a 1.5-2-fold increased risk for incident trichomonal, gonococcal, and/or chlamydial infection (adjusted hazard ratio [AHR] for intermediate state, 1.41 [95% confidence interval {CI}, 1.12-1.76]; AHR for BV, 1.73 [95% CI, 1.42-2.11]; Pp. 058 for trend). Estimates were similar for trichomonal-only, gonococcal-only, and chlamydial-only infection outcomes.
Conclusion. BV microbiota as gauged by Gram stain is associated with a significantly elevated risk for acquisition of trichomonal, gonococcal, and/or chlamydial genital infection.
C1 [Brotman, Rebecca M.] Univ Maryland, Sch Med, Inst Genome Sci, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Klebanoff, Mark A.; Nansel, Tonja R.; Yu, Kai F.; Zhang, Jun] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, US Dept HHS, Bethesda, MD USA.
[Andrews, William W.] Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA.
[Schwebke, Jane R.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA.
RP Brotman, RM (reprint author), Univ Maryland, Sch Med, Inst Genome Sci, Dept Epidemiol & Publ Hlth, BioPk Bldg 2,801 W Baltimore St,Room 633, Baltimore, MD 21201 USA.
EM rbrotman@som.umaryland.edu
RI Brotman, Rebecca/H-5442-2011;
OI Brotman, Rebecca/0000-0001-8762-6214; Nansel, Tonja/0000-0002-8298-7595
FU National Institute of Allergy and Infectious Diseases [K01-AI080974];
Eunice Kennedy Shriver National Institute of Child Health and Human
Development [NO-1-HD-8-3293, Z01 HD002535-10]
FX Financial support: National Institute of Allergy and Infectious Diseases
(grant K01-AI080974); Eunice Kennedy Shriver National Institute of Child
Health and Human Development (contract NO-1-HD-8-3293 and intramural
fund Z01 HD002535-10).
NR 50
TC 89
Z9 91
U1 1
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD DEC 15
PY 2010
VL 202
IS 12
BP 1907
EP 1915
DI 10.1086/657320
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 681XC
UT WOS:000284356300018
PM 21067371
ER
PT J
AU Kutty, G
Achaz, G
Maldarelli, F
Varma, A
Shroff, R
Becker, S
Fantoni, G
Kovacs, JA
AF Kutty, Geetha
Achaz, Guillaume
Maldarelli, Frank
Varma, Ashok
Shroff, Robert
Becker, Steven
Fantoni, Giovanna
Kovacs, Joseph A.
TI Characterization of the Meiosis-Specific Recombinase Dmc1 of
Pneumocystis
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID MAJOR SURFACE GLYCOPROTEIN; CARINII DIHYDROPTEROATE SYNTHASE; EXPRESSION
SITE; MEIOTIC RECOMBINATION; DIHYDROFOLATE-REDUCTASE; PHEROMONE
RECEPTOR; GENETIC DIVERSITY; MUTATIONS; HUMANS; RAD51
AB The life cycle of Pneumocystis, which causes life-threatening pneumonia in immunosuppressed patients, remains poorly defined. In the present study, we have identified and characterized an orthologue of dmc1, a gene specific for meiotic recombination in yeast, in 3 species of Pneumocystis. dmc1 is a single-copy gene that is transcribed as similar to 1.2-kb messenger RNA, which encodes a protein of 336-337 amino acids. Pneumocystis Dmc1 was 61%-70% identical to those from yeast. Confocal microscopy results indicated that the expression of Dmc1 is primarily confined to the cyst form of Pneumocystis. By sequence analysis of 2 single-copy regions of the human Pneumocystis jirovecii genome, we can infer multiple recombination events, which are consistent with meiotic recombination in this primarily haploid organism. Taken together, these studies support the occurrence of a sexual phase in the life cycle of Pneumocystis.
C1 [Achaz, Guillaume] Univ Paris 06, Paris, France.
[Maldarelli, Frank] NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21701 USA.
[Achaz, Guillaume] Unite Mixte Rech 7138 & Atelier Bioinformat, Paris, France.
[Shroff, Robert] NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Kutty, Geetha; Fantoni, Giovanna; Kovacs, Joseph A.] NIAID, Dept Crit Care Med, NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Varma, Ashok] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA.
[Becker, Steven] NIAID, Biol Imaging Facil, Bethesda, MD 20892 USA.
RP Kovacs, JA (reprint author), Bldg 10,Room 2C145,MSC 1662, Bethesda, MD 20892 USA.
EM jkovacs@nih.gov
FU National Institutes of Health Clinical Center; National Institute of
Allergy and Infectious Diseases; National Cancer Institute
FX Financial support: This research was supported by the Intramural
Research Programs of the National Institutes of Health Clinical Center,
the National Institute of Allergy and Infectious Diseases, and the
National Cancer Institute.
NR 50
TC 4
Z9 4
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD DEC 15
PY 2010
VL 202
IS 12
BP 1920
EP 1929
DI 10.1086/657414
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 681XC
UT WOS:000284356300020
PM 21050123
ER
PT J
AU Xue, L
Wu, LG
AF Xue, Lei
Wu, Ling-Gang
TI Post-tetanic potentiation is caused by two signalling mechanisms
affecting quantal size and quantal content
SO JOURNAL OF PHYSIOLOGY-LONDON
LA English
DT Article
ID TERM SYNAPTIC PLASTICITY; READILY RELEASABLE POOL; HELD SYNAPSE; RAT
CALYX; EVOKED NEUROTRANSMISSION; GLUTAMATE RECEPTORS; CA2+ CHANNELS;
VESICLES; DEPRESSION; TRANSMISSION
AB A high-frequency action potential train induces post-tetanic potentiation (PTP) of transmission at many synapses by increasing the intra-terminal calcium concentration, which may increase the quantal content by activation of protein kinase C (PKC). A recent study found that an increase of the mEPSC size, caused by compound vesicle fusion, parallels PTP, suggesting that the quantal size increase also contributes to the PTP generation. However, the strength of this suggestion is somewhat undermined by recent studies suggesting that vesicles responsible for spontaneous and evoked EPSCs may originate from different pools. Furthermore, it is unclear whether the quantal size increase is also mediated by PKC. The present work addressed these issues at a large calyx of Held synapse. We found that PTP was caused by both a PKC-dependent increase of the quantal content and a PKC-independent increase of the quantal size. In addition, we found that mEPSCs and EPSCs were subjected to similar up- and down-regulation, which verifies the basic assumption of quantal analysis - the same mechanism controls the quantal size of spontaneous and evoked release. This verification supports the use of quantal analysis at central synapses. However, unlike the traditional quantal analysis that attributes the quantal size change to a postsynaptic mechanism, the present work, together with one of our previous studies, suggests that the quantal size increase is caused by a presynaptic mechanism, the compound fusion among vesicles that forms large compound vesicles.
C1 [Xue, Lei; Wu, Ling-Gang] NINDS, Bethesda, MD 20892 USA.
RP Wu, LG (reprint author), NINDS, 35 Convent Dr,Bldg 35, Bethesda, MD 20892 USA.
EM wul@ninds.nih.gov
FU National Institute of Neurological Disorders and Stroke
FX We thank Drs Liming He and Fujun Luo for comments on the manuscript.
This work was supported by the National Institute of Neurological
Disorders and Stroke Intramural Research Program.
NR 35
TC 15
Z9 15
U1 1
U2 6
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-3751
J9 J PHYSIOL-LONDON
JI J. Physiol.-London
PD DEC 15
PY 2010
VL 588
IS 24
BP 4987
EP 4994
DI 10.1113/jphysiol.2010.196964
PG 8
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA 695HG
UT WOS:000285360600014
PM 21041528
ER
PT J
AU Chandran, PL
Dimitriadis, EK
Basser, PJ
Horkay, F
AF Chandran, Preethi L.
Dimitriadis, Emilios K.
Basser, Peter J.
Horkay, Ferenc
TI Probing Interactions between Aggrecan and Mica Surface by the Atomic
Force Microscopy
SO JOURNAL OF POLYMER SCIENCE PART B-POLYMER PHYSICS
LA English
DT Article
DE adsorption; aggrecan; atomic force microscopy; osmotic pressure
ID CONNECTIVE-TISSUE POLYSACCHARIDES; PHYSIOLOGICAL SALT-SOLUTIONS;
CARTILAGE AGGRECAN; ARTICULAR-CARTILAGE; MACROMOLECULES; PROTEOGLYCAN;
CALCIFICATION; NANOMECHANICS; PROTEIN; DNA
AB Aggrecan is a bottlebrush shaped macromolecule found in the extracellular matrix of cartilage. The negatively charged glycosaminoglycan (GAG) chains attached to its protein backbone give aggrecan molecules a high charge density, which is essential for exerting high osmotic swelling pressure and resisting compression under external load. In solution, aggrecan assemblies are insensitive to the presence of calcium ions, and show distinct osmotic pressure versus concentration regimes. The aim of this study is to investigate the effect of ionic environment on the structure of aggrecan molecules adsorbed onto well-controlled mica surfaces. The conformation of the aggrecan was visualized using Atomic Force Microscopy. On positively charged APS mica the GAG chains of the aggrecan molecules are distinguishable, and their average dimensions are practically unaffected by the presence of salt ions. With increasing aggrecan concentration they form clusters, and at higher concentrations they form a continuous monolayer of conforming molecules. On negatively charged mica, the extent of aggrecan adsorption varies with salt composition. Understanding aggrecan adsorption onto a charged surface provides insight into its interactions with bone and implant surfaces in the biological milieu. (C) 2010 Wiley Periodicals, Inc.dagger J Polym Sci Part B: Polym Phys 48: 2575-2581, 2010
C1 [Chandran, Preethi L.; Basser, Peter J.; Horkay, Ferenc] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Tissue Biophys & Biomimet, Program Pediat Imaging & Tissue Sci, NIH, Bethesda, MD 20892 USA.
[Chandran, Preethi L.; Dimitriadis, Emilios K.] Natl Inst Biomed Imaging & Bioengn, Lab Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA.
RP Chandran, PL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Tissue Biophys & Biomimet, Program Pediat Imaging & Tissue Sci, NIH, Bethesda, MD 20892 USA.
EM chandranlp@mail.nih.gov; horkay@helix.nih.gov
RI Basser, Peter/H-5477-2011
FU NIH, NICHD
FX This work was supported by the Intramural Research Program of the NIH,
NICHD.
NR 33
TC 2
Z9 2
U1 1
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0887-6266
J9 J POLYM SCI POL PHYS
JI J. Polym. Sci. Pt. B-Polym. Phys.
PD DEC 15
PY 2010
VL 48
IS 24
BP 2575
EP 2581
DI 10.1002/polb.22132
PG 7
WC Polymer Science
SC Polymer Science
GA 680JN
UT WOS:000284228300010
PM 22473175
ER
PT J
AU Zheng, YL
Hu, YF
Zhang, AP
Wang, W
Li, B
Amin, N
Grant, P
Pant, HC
AF Zheng, Ya-Li
Hu, Ya-Fang
Zhang, AiPing
Wang, Wei
Li, Bo
Amin, Niranjana
Grant, Philip
Pant, Harish C.
TI Overexpression of p35 in Min6 pancreatic beta cells induces a stressed
neuron-like apoptosis
SO JOURNAL OF THE NEUROLOGICAL SCIENCES
LA English
DT Article; Proceedings Paper
CT 1st Congress on Vascular Dementia (VaD)
CY 2009
CL Geneva, SWITZERLAND
DE Cdk5 activity; p35; Pancreatic beta cells; Insulin secretion
ID DEPENDENT KINASE-5 ACTIVITY; ALZHEIMERS-DISEASE; DIABETES-MELLITUS;
INSULIN-SECRETION; CDK5 ACTIVITY; ACTIVATOR; GLUCOSE; EXPRESSION; P25;
PHOSPHORYLATION
AB Cdk5 activity has been implicated in brain development and the regulation of many neuronal processes. Recently, the expression of p35 and Cdk5 activity has been reported in pancreatic beta cells. Decreased Cdk5 activity enhanced glucose-stimulated insulin secretion. This suggests that Cdk5 may play an important role in the regulation of insulin secretion. To further understand how Cdk5 regulates insulin secretion in glucose-stimulated pancreatic beta cells, we first confirmed the presence of a low level of p35 in pancreatic Min6 cells. Next, in a time-course experiment in high glucose (25 mM) we showed that endogenous p35 increased gradually accompanied by a 3-fold increase in Cdk5 activity by 16 h. Insulin secretion, however, doubled after 2 h followed by progressive downregulation, negatively correlated with Cdk5 activity. On the other hand, overexpression of p35 in these cells resulted in more than a three-fold increase in Cdk5 activity within 2 h coupled to a 50% reduction in insulin secretion in both high and low (3 mM) glucose. Most significantly, cells overexpressing p35, treated with high glucose for 4 h, showed induction of p25, the p35-derived truncated fragment which hyperactivates Cdk5 in neurons. As a result, insulin secretion was inhibited and cells became apoptotic. Roscovitine or co-infection of dominant negative Cdk5 (dnCdk5) with p35 increased insulin secretion and inhibited apoptosis. These results suggest that the model for deregulation and hyperactivation of Cdk5 in neurodegeneration may apply to the pathology seen in type 2 diabetes (T2DM). It is consistent with the view that Alzheimer's disease and T2DM are linked metabolically and pathologically by Cdk5 in a number of ways. (C) 2010 Published by Elsevier B.V.
C1 [Zheng, Ya-Li; Wang, Wei; Li, Bo] Peoples Hosp Ningxia Prov, Dept Nephrol, Yinchuan 750021, Ningxia Prov, Peoples R China.
[Zheng, Ya-Li; Amin, Niranjana; Grant, Philip; Pant, Harish C.] NINDS, Lab Neurochem LNC, NIH, Bethesda, MD 20892 USA.
[Hu, Ya-Fang; Zhang, AiPing] NIDCR, OIIB, NIH, Bethesda, MD 20892 USA.
RP Zheng, YL (reprint author), Ningxia Peoples Hosp, Dept Nephrol, Yinchuan 750021, Ningxia Prov, Peoples R China.
EM yalinew@yahoo.com
FU Intramural NIH HHS
NR 31
TC 8
Z9 8
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0022-510X
J9 J NEUROL SCI
JI J. Neurol. Sci.
PD DEC 15
PY 2010
VL 299
IS 1-2
SI SI
BP 101
EP 107
DI 10.1016/j.jns.2010.08.067
PG 7
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 705JC
UT WOS:000286123700023
PM 20926102
ER
PT J
AU Emerman, AB
Zhang, ZR
Chakrabarti, O
Hegde, RS
AF Emerman, Amy B.
Zhang, Zai-Rong
Chakrabarti, Oishee
Hegde, Ramanujan S.
TI Compartment-Restricted Biotinylation Reveals Novel Features of Prion
Protein Metabolism in Vivo
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID SIGNAL RECOGNITION PARTICLE; SINGLE TRANSLATION PRODUCT; IRON-SULFUR
CLUSTER; ENDOPLASMIC-RETICULUM; TRANSMEMBRANE FORM;
GLUCOCORTICOID-RECEPTOR; REGULATED EXPRESSION; NASCENT PREPROLACTIN;
MAMMALIAN-CELLS; MITOCHONDRIAL
AB Proteins are often made in more than one form, with alternate versions sometimes residing in different cellular compartments than the primary species. The mammalian prion protein (PrP), a cell surface GPI-anchored protein, is a particularly noteworthy example for which minor cytosolic and transmembrane forms have been implicated in disease pathogenesis. To study these minor species, we used a selective labeling strategy in which spatially restricted expression of a biotinylating enzyme was combined with asymmetric engineering of the cognate acceptor sequence into PrP. Using this method, we could show that even wild-type PrP generates small amounts of the (Ctm)PrP transmembrane form. Selective detection of (Ctm)PrP allowed us to reveal its N-terminal processing, long half-life, residence in both intracellular and cell surface locations, and eventual degradation in the lysosome. Surprisingly, some human disease-causing mutants in PrP selectively stabilized (Ctm)PrP, revealing a previously unanticipated mechanism of (Ctm)PrP up-regulation that may contribute to disease. Thus, spatiotemporal tagging has uncovered novel aspects of normal and mutant PrP metabolism and should be readily applicable to the analysis of minor topologic isoforms of other proteins.
C1 [Emerman, Amy B.; Zhang, Zai-Rong; Chakrabarti, Oishee; Hegde, Ramanujan S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
RP Hegde, RS (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
EM hegder@mail.nih.gov
RI Zhang, Zairong/G-1030-2013;
OI Hegde, Ramanujan/0000-0001-8338-852X
FU National Institute of Child Health and Human Development at the National
Institutes of Health
FX We thank members of the Hegde Lab, particularly Aarthi Ashok, for useful
discussions. This work was supported by the Intramural Research Program
of the National Institute of Child Health and Human Development at the
National Institutes of Health.
NR 62
TC 18
Z9 19
U1 0
U2 6
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD DEC 15
PY 2010
VL 21
IS 24
BP 4325
EP 4337
DI 10.1091/mbc.E10-09-0742
PG 13
WC Cell Biology
SC Cell Biology
GA 695AP
UT WOS:000285343300004
PM 20980618
ER
PT J
AU Herath, P
Gallea, C
van der Veen, JW
Horovitz, SG
Hallett, M
AF Herath, Priyantha
Gallea, Cecile
van der Veen, Jan Willem
Horovitz, Silvina G.
Hallett, Mark
TI In Vivo Neurochemistry of Primary Focal Hand Dystonia: A Magnetic
Resonance Spectroscopic Neurometabolite Profiling Study at 3T
SO MOVEMENT DISORDERS
LA English
DT Article
DE dystonia; magnetic resonance spectroscopy; gamma amino butyric acid
(GABA); metabolic profile; imaging
ID HUMAN BRAIN; SURROUND INHIBITION; PREMOTOR CORTEX; GABA; SPECTRA; MOTOR;
NEUROTRANSMITTER; PATHOPHYSIOLOGY; METABOLITES; GLUTAMATE
AB The neurochemical basis of dystonia is unknown. The purpose of this study was to assess the differences of the inhibitory neurotransmitter, gamma amino butyric acid (GABA), in the sensorimotor cortex and the basal ganglia using magnetic resonance spectroscopy with optimized GABA sensitivity. Twenty-two patients with focal hand dystonia and 22 healthy controls were studied. No significant differences in GABA were observed between the groups in either the sensorimotor cortex or in the basal ganglia. (C) 2010 Movement Disorder Society
C1 [Herath, Priyantha; Gallea, Cecile; Horovitz, Silvina G.; Hallett, Mark] NINDS, Med Neurol Branch, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA.
[van der Veen, Jan Willem] NIMH, MRS Core Facil, NIH, Bethesda, MD 20892 USA.
RP Herath, P (reprint author), NINDS, Med Neurol Branch, Human Motor Control Sect, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM herapx@gmail.com
FU NIH through US federal government; NINDS; US Army; Ariston
Pharmaceuticals; Kinetics Foundation; NIH
FX Alan Barnet helped us with the algorithm that we used for segmenting the
voxels into white matter and grey matter compartments. This work was
carried out with intramural funding from the NIH- available through US
federal government funds. None of the authors have received, or are
expected to receive any other funding.; All funding for the work are
from the NINDS intramural budget. Dr. Hallett reports: Consulting and
Advisory Board Membership with honoraria: Neurotoxin Institute;
Grants/Research: Funding from NIH, the US Army, Ariston Pharmaceuticals,
Kinetics Foundation; Honoraria: University of Navarra, State of New
York, University of Wisconsin, Massachusetts Medical Society, Parkinson
and Aging Research Society, Columbia University; Intellectual Property
Rights: H-coil; Royalties: Wiley-Blackwell, Oxford University Press,
Lippincott, Wilkins and Williams, Cambridge University Press, Elsevier
Publishers, Springer.
NR 31
TC 9
Z9 10
U1 0
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0885-3185
J9 MOVEMENT DISORD
JI Mov. Disord.
PD DEC 15
PY 2010
VL 25
IS 16
BP 2800
EP 2808
DI 10.1002/mds.23306
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA 703LK
UT WOS:000285979200015
PM 20979122
ER
PT J
AU Carol, H
Morton, CL
Gorlick, R
Kolb, EA
Keir, ST
Reynolds, CP
Kang, MH
Maris, JM
Billups, C
Smith, MA
Houghton, PJ
Lock, RB
AF Carol, Hernan
Morton, Christopher L.
Gorlick, Richard
Kolb, E. Anders
Keir, Stephen T.
Reynolds, C. Patrick
Kang, Min H.
Maris, John M.
Billups, Catherine
Smith, Malcolm A.
Houghton, Peter J.
Lock, Richard B.
TI Initial Testing (Stage 1) of the Akt Inhibitor GSK690693 by the
Pediatric Preclinical Testing Program
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE Akt inhibitor; developmental therapeutics; preclinical testing
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; HUMAN NEUROBLASTOMA-CELLS; GROWTH-FACTOR;
IN-VIVO; ANTITUMOR-ACTIVITY; KINASE INHIBITOR; 3-KINASE PATHWAY; CANCER
MODELS; CHEMOTHERAPY; ACTIVATION
AB Background GSK690693 is a small molecule ATP competitive inhibitor of the pro survival kinase Akt Since Akt regulates multiple downstream targets including transcription factors, glycogen synthase 3 the pro apoptotic protein Bid is well as MDM2 and mTORC1, it was tested against the in vitro and in vivo panels of the Pediatric Preclinical Testing Program (PPTP) Procedures GSK690693 was tested in vitro at concentrations from 1 nM to 10 mu M and against the in vivo panel of xenografts at a dose of 30 mg/kg daily x 5 for 6 consecutive weeks Three measures of in vivo antitumor activity were used (1) an objective response measure modeled after the clinical setting (2) a treated to control (TIC) tumor volume measure and (3) a time to event measure based on the median event free survival (EFS) of treated and control animals for each xenograft Results GSK690693 inhibited cell growth in vitro with IC(50) values between 6 5 nM and >10 mu M In vivo GSK690693 significantly increased EFS in 11 of 34 (32%) solid tumor xenografts most notably in all 6 osteosarcoma models but not in any of the 8 ALL xenografts tested No objective responses were observed and only one solid tumor met EFS TIC criteria for intermediate activity Conclusions GSK690693 demonstrated broad activity in vitro, how ever our results against both the solid tumor and ALL PPTP in vivo panels demonstrate that, as single agent at the dose and schedule used GSK690693 has only modest antitumor activity Pediatr Blood Cancer 2010 55 1329-1337 (C) 2010 Wiley Liss Inc
C1 [Lock, Richard B.] Lowy Canc Res Ctr, Childrens Canc Inst Australia Med Res, Randwick, NSW 2031, Australia.
[Morton, Christopher L.; Billups, Catherine] St Jude Childrens Hosp, Memphis, TN 38105 USA.
[Gorlick, Richard] Childrens Hosp Montefiore, Bronx, NY USA.
[Kolb, E. Anders] Alfred I DuPont Hosp Children, Wilmington, DE 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.
[Maris, John M.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA.
[Maris, John M.] Abramson Family Canc Res Inst, Philadelphia, PA USA.
[Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Houghton, Peter J.] Nationwide Childrens Hosp, Columbus, OH USA.
RP Lock, RB (reprint author), Lowy Canc Res Ctr, Childrens Canc Inst Australia Med Res, Randwick, NSW 2031, Australia.
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 This work was supported by NO1-CM-42216, CA21765 and CA108786 from the
National Cancer Institute and used GSK690693 supplied by GlaxoSmithKline
In addition to the authors this study represents work contributed by the
following Sherry Ansher Catherine A Billups Ingrid Boehm Joshua
Courtright Mila Dolotin Edward Favours, Henry S Friedman Debbie
Payne-Turner Charles Stopford Chandra Tucker, Amy E Watkins Joe Zeidner,
Ellen Zhang and Jian Zhang Children s Cancer Institute Australia for
Medical Research is affiliated with the University of New South Wales
and Sydney Children s Hospital
NR 37
TC 25
Z9 25
U1 0
U2 5
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD DEC 15
PY 2010
VL 55
IS 7
BP 1329
EP 1337
DI 10.1002/pbc.22710
PG 9
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 677WB
UT WOS:000284023600015
PM 20740623
ER
PT J
AU Dauvillee, D
Delhaye, S
Gruyer, S
Slomianny, C
Moretz, SE
d'Hulst, C
Long, CA
Ball, SG
Tomavo, S
AF Dauvillee, David
Delhaye, Stephane
Gruyer, Sebastien
Slomianny, Christian
Moretz, Samuel E.
d'Hulst, Christophe
Long, Carole A.
Ball, Steven G.
Tomavo, Stanislas
TI Engineering the Chloroplast Targeted Malarial Vaccine Antigens in
Chlamydomonas Starch Granules
SO PLOS ONE
LA English
DT Article
ID PLASMODIUM-FALCIPARUM MALARIA; APICAL MEMBRANE ANTIGEN-1; BLOOD-STAGE
VACCINE; IN-VITRO; REINHARDTII; AMYLOPECTIN; INVASION; AMYLOSE;
BIOSYNTHESIS; ANTIBODIES
AB Background: Malaria, an Anopheles-borne parasitic disease, remains a major global health problem causing illness and death that disproportionately affects developing countries. Despite the incidence of malaria, which remains one of the most severe infections of human populations, there is no licensed vaccine against this life-threatening disease. In this context, we decided to explore the expression of Plasmodium vaccine antigens fused to the granule bound starch synthase (GBSS), the major protein associated to the starch matrix in all starch-accumulating plants and algae such as Chlamydomonas reinhardtii.
Methods and Findings: We describe the development of genetically engineered starch granules containing plasmodial vaccine candidate antigens produced in the unicellular green algae Chlamydomonas reinhardtii. We show that the C-terminal domains of proteins from the rodent Plasmodium species, Plasmodium berghei Apical Major Antigen AMA1, or Major Surface Protein MSP1 fused to the algal granule bound starch synthase (GBSS) are efficiently expressed and bound to the polysaccharide matrix. Mice were either immunized intraperitoneally with the engineered starch particles and Freund adjuvant, or fed with the engineered particles co-delivered with the mucosal adjuvant, and challenged intraperitoneally with a lethal inoculum of P. Berghei. Both experimental strategies led to a significantly reduced parasitemia with an extension of life span including complete cure for intraperitoneal delivery as assessed by negative blood thin smears. In the case of the starch bound P. falciparum GBSS-MSP1 fusion protein, the immune sera or purified immunoglobulin G of mice immunized with the corresponding starch strongly inhibited in vitro the intra-erythrocytic asexual development of the most human deadly plasmodial species.
Conclusion: This novel system paves the way for the production of clinically relevant plasmodial antigens as algal starch-based particles designated herein as amylosomes, demonstrating that efficient production of edible vaccines can be genetically produced in Chlamydomonas.
C1 [Dauvillee, David; Delhaye, Stephane; Gruyer, Sebastien; d'Hulst, Christophe; Ball, Steven G.; Tomavo, Stanislas] Univ Sci & Technol Lille, CNRS, UGSF, UMR 8576, Villeneuve Dascq, France.
[Delhaye, Stephane; Tomavo, Stanislas] Univ Lille Nord France, Inst Pasteur Lille, INSERM, Ctr Infect & Immun Lille,CNRS,UMR 8204,U1019, Lille, France.
[Slomianny, Christian] Univ Sci & Technol Lille, INSERM, U1003, Lab Physiol Cellulaire, Villeneuve Dascq, France.
[Moretz, Samuel E.; Long, Carole A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
RP Dauvillee, D (reprint author), Univ Sci & Technol Lille, CNRS, UGSF, UMR 8576, Villeneuve Dascq, France.
EM Stan.Tomavo@pasteur-lille.fr
OI Ball, Steven/0000-0003-1629-1650; Dauvillee, David/0000-0002-0751-9193
FU Centre National de la Recherche Scientifique (CNRS); Institut Medicale
de la Recherche Scientifique (INSERM); Institut Pasteur de Lille (IPL)
FX This research was funded by the Centre National de la Recherche
Scientifique (CNRS), Institut Medicale de la Recherche Scientifique
(INSERM) and the Institut Pasteur de Lille (IPL). The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 34
TC 24
Z9 25
U1 0
U2 11
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD DEC 15
PY 2010
VL 5
IS 12
AR e15424
DI 10.1371/journal.pone.0015424
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 694ZI
UT WOS:000285340000025
PM 21179538
ER
PT J
AU Jeang, KT
AF Jeang, Kuan-Teh
TI The rise of Bioscience in the East
SO RETROVIROLOGY
LA English
DT Editorial Material
AB The rapid growth of bioscience in China is considered.
C1 NIH, Bethesda, MD 20892 USA.
RP Jeang, KT (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
EM kjeang@niaid.nih.gov
RI Jeang, Kuan-Teh/A-2424-2008
FU Intramural NIH HHS
NR 9
TC 2
Z9 2
U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-4690
J9 RETROVIROLOGY
JI Retrovirology
PD DEC 15
PY 2010
VL 7
AR 106
DI 10.1186/1742-4690-7-106
PG 2
WC Virology
SC Virology
GA 700ZV
UT WOS:000285785000001
PM 21159179
ER
PT J
AU Andersen, JF
AF Andersen, John F.
TI Structure and mechanism in salivary proteins from blood-feeding
arthropods
SO TOXICON
LA English
DT Article; Proceedings Paper
CT 16th World Congress of the International-Society-on-Toxinology/10th
Congress of the Brazilian-Society-Toxicology
CY MAR, 2009
CL BRAZIL
SP Int Soc Toxinol (IST), Brazilian Soc Toxicol
DE Lipocalin; Odorant-binding protein; D7; Nitrophorin; Tick; Mosquito;
Diptera; X-ray crystallography
ID BUG RHODNIUS-PROLIXUS; NITRIC-OXIDE-BINDING; HISTAMINE-BINDING;
BLOODSUCKING BUG; HEME PROTEIN; CRYSTAL-STRUCTURE; LIGAND-BINDING;
ANTIHEMOSTATIC PROTEIN; COMPLEMENT INHIBITOR; PLATELET-AGGREGATION
AB The saliva of blood-feeding arthropods contains rich mixtures of ligand binding proteins targeted at inhibiting hemostasis and inflammation in the host. Since blood feeding has evolved many times, different taxonomic groups utilize completely different families of proteins to perform similar tasks. Structural studies performed on a number of these proteins have revealed biologically novel and sophisticated mechanisms used to perform their functions. Here, the results of these structural and mechanistic studies are reviewed. Published by Elsevier Ltd.
C1 NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
RP Andersen, JF (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 2E-32B Twinbrook 3 Bldg,12735 Twinbrook Pkwy, Rockville, MD 20852 USA.
EM jandersen@niaid.nih.gov
FU Intramural NIH HHS [Z01 AI001012-01]
NR 52
TC 20
Z9 20
U1 1
U2 15
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0041-0101
J9 TOXICON
JI Toxicon
PD DEC 15
PY 2010
VL 56
IS 7
SI SI
BP 1120
EP 1129
DI 10.1016/j.toxicon.2009.11.002
PG 10
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA 710XM
UT WOS:000286550300006
PM 19925819
ER
PT J
AU Francischetti, IMB
AF Francischetti, Ivo M. B.
TI Platelet aggregation inhibitors from hematophagous animals
SO TOXICON
LA English
DT Article; Proceedings Paper
CT 16th World Congress of the International-Society-on-Toxinology/10th
Congress of the Brazilian-Society-Toxicology
CY MAR, 2009
CL BRAZIL
SP Int Soc Toxinol (IST), Brazilian Soc Toxicol
DE Platelet aggregation; Hematophagy; Thrombosis; Vascular biology;
Sialogenins
ID VON-WILLEBRAND-FACTOR; LEECH ANTIPLATELET PROTEIN;
GLYCOPROTEIN-IIB-IIIA; HAEMENTERIA-OFFICINALIS LEECH; TICK
ORNITHODOROS-MOUBATA; BLOOD-FEEDING INSECT; FORMATION IN-VIVO;
SALIVARY-GLANDS; SOFT TICK; RHODNIUS-PROLIXUS
AB Salivary glands from blood-sucking animals (e.g., mosquitoes, bugs, sand flies, fleas, ticks, leeches, hookworms, bats) are a rich source of bioactive molecules that counteract hemostasis in a redundant and synergistic manner. This review discusses recent progress in the identification of salivary inhibitors of platelet aggregation, their molecular characterization, and detailed mechanism of action. Diversity of inhibitors is remarkable, with distinct families of proteins characterized as apyrases that enzymatically degrade ADP or as collagen-binding proteins that prevent its interaction with vWF, or platelet integrin alpha 2 beta 1 or GPVI. Molecules that bind ADP. TXA(2), epinephrine, or serotonin with high affinity have also been cloned, expressed, and their structure determined. In addition, a repertoire of antithrombins and an increasingly number of RGD and non-RGD disintegrins targeting platelet alpha IIb beta 3 have been reported. Moreover, metalloproteases with fibrinogen(olytic) activity and PAF phosphorylcholine hydrolase are enzymes that have been recruited to the salivary gland to block platelet aggregation. Platelet inhibitory prostaglandins, lysophosphatydilcholine, adenosine, and nitric oxide (NO)-carrying proteins are other notable examples of molecules from hematophagous salivary secretions (herein named sialogenins) with antihemostatic properties. Sialogenins have been employed as tools in biochemistry and cell biology and also display potential therapeutic applications. Published by Elsevier Ltd.
C1 NIAID, Vector Biol Sect, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
RP Francischetti, IMB (reprint author), NIAID, Vector Biol Sect, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM ifrancischetti@niaid.nih.gov
FU Intramural NIH HHS [Z01 AI000810-11, Z99 AI999999]
NR 85
TC 54
Z9 55
U1 1
U2 13
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0041-0101
J9 TOXICON
JI Toxicon
PD DEC 15
PY 2010
VL 56
IS 7
SI SI
BP 1130
EP 1144
DI 10.1016/j.toxicon.2009.12.003
PG 15
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA 710XM
UT WOS:000286550300007
PM 20035779
ER
PT J
AU Pasha, O
Goldenberg, RL
McClure, EM
Saleem, S
Goudar, SS
Althabe, F
Patel, A
Esamai, F
Garces, A
Chomba, E
Mazariegos, M
Kodkany, B
Belizan, JM
Derman, RJ
Hibberd, PL
Carlo, WA
Liechty, EA
Hambidge, KM
Buekens, P
Wallace, D
Howard-Grabman, L
Stalls, S
Koso-Thomas, M
Jobe, AH
Wright, LL
AF Pasha, Omrana
Goldenberg, Robert L.
McClure, Elizabeth M.
Saleem, Sarah
Goudar, Shivaprasad S.
Althabe, Fernando
Patel, Archana
Esamai, Fabian
Garces, Ana
Chomba, Elwyn
Mazariegos, Manolo
Kodkany, Bhala
Belizan, Jose M.
Derman, Richard J.
Hibberd, Patricia L.
Carlo, Waldemar A.
Liechty, Edward A.
Hambidge, K. Michael
Buekens, Pierre
Wallace, Dennis
Howard-Grabman, Lisa
Stalls, Suzanne
Koso-Thomas, Marion
Jobe, Alan H.
Wright, Linda L.
TI Communities, birth attendants and health facilities: a continuum of
emergency maternal and newborn care (the global network's EmONC trial)
SO BMC PREGNANCY AND CHILDBIRTH
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; OBSTETRIC CARE; DEVELOPING-COUNTRIES;
PERINATAL-MORTALITY; NEONATAL DEATHS; SURVIVAL 1; NEPAL; INTERVENTION;
PREPAREDNESS; STILLBIRTH
AB Background: Maternal and newborn mortality rates remain unacceptably high, especially where the majority of births occur in home settings or in facilities with inadequate resources. The introduction of emergency obstetric and newborn care services has been proposed by several organizations in order to improve pregnancy outcomes. However, the effectiveness of emergency obstetric and neonatal care services has never been proven. Also unproven is the effectiveness of community mobilization and community birth attendant training to improve pregnancy outcomes.
Methods/Design: We have developed a cluster-randomized controlled trial to evaluate the impact of a comprehensive intervention of community mobilization, birth attendant training and improvement of quality of care in health facilities on perinatal mortality in low and middle-income countries where the majority of births take place in homes or first level care facilities. This trial will take place in 106 clusters (300-500 deliveries per year each) across 7 sites of the Global Network for Women's and Children's Health Research in Argentina, Guatemala, India, Kenya, Pakistan and Zambia. The trial intervention has three key elements, community mobilization, home-based life saving skills for communities and birth attendants, and training of providers at obstetric facilities to improve quality of care. The primary outcome of the trial is perinatal mortality. Secondary outcomes include rates of stillbirth, 7-day neonatal mortality, maternal death or severe morbidity (including obstetric fistula, eclampsia and obstetrical sepsis) and 28-day neonatal mortality.
Discussion: In this trial, we are evaluating a combination of interventions including community mobilization and facility training in an attempt to improve pregnancy outcomes. If successful, the results of this trial will provide important information for policy makers and clinicians as they attempt to improve delivery services for pregnant women and newborns in low-income countries.
C1 [Pasha, Omrana; Saleem, Sarah] Aga Khan Univ, Dept Community Hlth Sci, Karachi, Pakistan.
[Goldenberg, Robert L.] Drexel Univ, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA.
[McClure, Elizabeth M.; Wallace, Dennis] Res Triangle Inst, Dept Stat & Epidemiol, Durham, NC USA.
[Goudar, Shivaprasad S.; Kodkany, Bhala] Jawaharlal Nehru Med Coll, KLE Res Fdn, Belgaum, India.
[Althabe, Fernando; Belizan, Jose M.] Univ Buenos Aires, Inst Clin Effectiveness & Hlth Policy, Buenos Aires, DF, Argentina.
[Patel, Archana] Indira Gandhi Govt Med Coll, Dept Pediat, Nagpur, Maharashtra, India.
[Esamai, Fabian] Moi Univ, Dept Pediat, Eldoret, Kenya.
[Garces, Ana] San Carlos Univ, Guatemala City, Guatemala.
[Chomba, Elwyn] Univ Zambia, Dept Pediat, Lusaka, Zambia.
[Mazariegos, Manolo] ECLAMP, Guatemala City, Guatemala.
[Derman, Richard J.] Christiana Hlth Care, Dept Obstet & Gynecol, Delaware, OH USA.
[Hibberd, Patricia L.] Partners Hlth Org, Boston, MA USA.
[Carlo, Waldemar A.] Univ Alabama Birmingham, Dept Pediat, Birmingham, AL USA.
[Liechty, Edward A.] Indiana Univ, Dept Pediat, Indianapolis, IN 46204 USA.
[Hambidge, K. Michael] Univ Colorado, Denver, CO 80202 USA.
[Buekens, Pierre] Tulane Sch Publ Hlth & Trop Med, New Orleans, LA USA.
[Howard-Grabman, Lisa] TRG Inc, Alexandria, VA USA.
[Koso-Thomas, Marion; Wright, Linda L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Jobe, Alan H.] Cincinnati Childrens Hosp, Dept Pediat, Cincinnati, OH USA.
RP Pasha, O (reprint author), Aga Khan Univ, Dept Community Hlth Sci, Karachi, Pakistan.
EM omrana.pasha@aku.edu
OI GOUDAR, SHIVAPRASAD/0000-0002-8680-7053; Belizan,
Jose/0000-0002-8412-3010
FU Eunice Kennedy Shriver National Institute on Child Health and Human
Development; Eunice Kennedy Shriver National Institute of Child health
and Human Development (NICHD), of the National Institutes of Health in
the United States
FX This project is funded by grants from the Eunice Kennedy Shriver
National Institute on Child Health and Human Development.; This project
is being funded by the Eunice Kennedy Shriver National Institute of
Child health and Human Development (NICHD), of the National Institutes
of Health in the United States. The authors of this paper have no
competing interests to declare.
NR 59
TC 31
Z9 32
U1 4
U2 15
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2393
J9 BMC PREGNANCY CHILDB
JI BMC Pregnancy Childbirth
PD DEC 14
PY 2010
VL 10
AR 82
DI 10.1186/1471-2393-10-82
PG 9
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 840RB
UT WOS:000296457300001
PM 21156060
ER
PT J
AU Yaseen, Z
Katz, C
Johnson, MS
Eisenberg, D
Cohen, LJ
Galynker, II
AF Yaseen, Zimri
Katz, Curren
Johnson, Matthew S.
Eisenberg, Daniel
Cohen, Lisa J.
Galynker, Igor I.
TI Construct development: The Suicide Trigger Scale (STS-2), a measure of a
hypothesized suicide trigger state
SO BMC PSYCHIATRY
LA English
DT Article
ID SEQUENCED TREATMENT ALTERNATIVES; RISK-FACTORS; PSYCHOLOGICAL DISTRESS;
ASTERISK-D; IDEATION; BEHAVIOR; DEPRESSION; ADOLESCENTS; COMORBIDITY;
PREVENTION
AB Background: This study aims to develop the construct of a 'suicide trigger state' by exploring data gathered with a novel psychometric self-report instrument, the STS-2.
Methods: The STS-2, was administered to 141 adult psychiatric patients with suicidal ideation. Multiple statistical methods were used to explore construct validity and structure.
Results: Cronbach's alpha (0.949) demonstrated excellent internal consistency. Factor analyses yielded two-component solutions with good agreement. The first component described near-psychotic somatization and ruminative flooding, while the second described frantic hopelessness. ROC analysis determined an optimal cut score for a history of suicide attempt, with significance of p < 0.03. Logistic regression analysis found items sensitive to history of suicide attempt described ruminative flooding, doom, hopelessness, entrapment and dread.
Conclusions: The STS-2 appears to measure a distinct and novel clinical entity, which we speculatively term the 'suicide trigger state.' High scores on the STS-2 associate with reported history of past suicide attempt.
C1 [Yaseen, Zimri; Katz, Curren; Cohen, Lisa J.; Galynker, Igor I.] Beth Israel Deaconess Med Ctr, New York, NY 10003 USA.
[Johnson, Matthew S.] Columbia Univ, Teachers Coll, New York, NY 10027 USA.
[Eisenberg, Daniel] NIMH, Bethesda, MD 20892 USA.
RP Yaseen, Z (reprint author), Beth Israel Deaconess Med Ctr, New York, NY 10003 USA.
EM zsyaseen@gmail.com
RI Eisenberg, Daniel/C-7432-2014; Katz, Curren/J-4197-2014; Eisenberg,
Daniel/S-4342-2016;
OI Katz, Curren/0000-0002-0125-9861; Yaseen, Zimri/0000-0003-4103-2511;
Johnson, Matthew/0000-0003-3157-4165
FU Hope for Depression Research Foundation; Empire Clinical Research
Investigator Program; Family Center for Bipolar Disorder; Zirinsky Mood
Disorders Center
FX This research was supported in part by the Hope for Depression Research
Foundation, the Empire Clinical Research Investigator Program, the
Family Center for Bipolar Disorder, and the Zirinsky Mood Disorders
Center. This research was presented in part at the following meetings:
Yaseen Z, Johnson M, Galynker I. Construct Validity of a Suicide Trigger
State. The 162nd Annual Meeting of the American Psychiatric Association,
San Francisco, CA (2009)
NR 48
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U1 3
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-244X
J9 BMC PSYCHIATRY
JI BMC Psychiatry
PD DEC 14
PY 2010
VL 10
AR 110
DI 10.1186/1471-244X-10-110
PG 11
WC Psychiatry
SC Psychiatry
GA 702WM
UT WOS:000285926600001
PM 21144063
ER
PT J
AU den Elzen, WPJ
Willems, JM
Westendorp, RGJ
de Craen, AJM
Blauw, GJ
Ferrucci, L
Assendelft, WJJ
Gussekloo, J
AF den Elzen, Wendy P. J.
Willems, Jorien M.
Westendorp, Rudi G. J.
de Craen, Anton J. M.
Blauw, Gerard Jan
Ferrucci, Luigi
Assendelft, Willem J. J.
Gussekloo, Jacobijn
TI Effect of erythropoietin levels on mortality in old age: the Leiden
85-plus Study
SO CANADIAN MEDICAL ASSOCIATION JOURNAL
LA English
DT Article
ID RECOMBINANT-HUMAN-ERYTHROPOIETIN; CONGESTIVE-HEART-FAILURE; ENDOGENOUS
ERYTHROPOIETIN; SERUM ERYTHROPOIETIN; PROGNOSTIC VALUE; EPOETIN-ALPHA;
METAANALYSIS; CANCER; PREDICTION; QUALITY
AB Background: The production of erythropoietin is triggered by impaired oxygen delivery to the kidney, either because of anemia or hypoxemia. High erythropoietin levels have been shown to predict the risk of death among patients with chronic heart failure. We investigated the prognostic value of elevated erythropoietin levels on mortality among very elderly people in the general population.
Methods: The Leiden 85-plus Study is a population-based prospective follow-up study involving 599 people aged 85 years in Leiden, the Netherlands, enrolled between September 1997 and September 1999. Erythropoietin levels were determined at age 86. For this analysis, we included 428 participants with a creatinine clearance of at least 30 mL/min. Mortality data, recorded until Feb. 1, 2008, were obtained from the municipal registry.
Results: During follow-up, 324 (75.7%) participants died. Compared with participants whose erythropoietin levels were in the lowest tertile (reference group), those whose levels were in the middle tertile had a 25% increased risk of death (hazard ratio [HR] 1.25, 95% confidence interval [CI] 0.95-1.64), and those whose levels were in the highest tertile had a 73% increased risk (HR 1.73, 95% CI 1.32-2.26) (p value for trend < 0.01). The association between erythropoietin levels and mortality remained largely unchanged after we adjusted for sex, creatinine clearance, hemoglobin level, comorbidity, smoking status and C-reactive protein level, and was similar for deaths from cardiovascular and noncardiovascular causes.
Interpretation: Among people aged 85 years and older, elevated erythropoietin levels were associated with an in creased risk of death, independent of hemoglobin levels.
C1 [den Elzen, Wendy P. J.; Assendelft, Willem J. J.; Gussekloo, Jacobijn] Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, NL-2300 RC Leiden, Netherlands.
[Willems, Jorien M.; Westendorp, Rudi G. J.; de Craen, Anton J. M.; Blauw, Gerard Jan] Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, NL-2300 RC Leiden, Netherlands.
[Westendorp, Rudi G. J.] Netherlands Consortium Healthy Ageing, Leiden, Netherlands.
[Blauw, Gerard Jan] Bronovo Hosp, Dept Internal Med, The Hague, Netherlands.
[Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA.
RP den Elzen, WPJ (reprint author), Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, POB 9600, NL-2300 RC Leiden, Netherlands.
EM w.p.j.den_elzen@lumc.nl
RI Assendelft, W.J.J./H-8008-2014
FU Dutch Ministry of Health, Welfare and Sports; US National Institute on
Aging, National Institute of Health
FX The Leiden 85-plus Study was funded in part by an unrestricted grant
from the Dutch Ministry of Health, Welfare and Sports. This study was
supported by the Intramural Research Program of the US National
Institute on Aging, National Institute of Health. The sponsor had no
role in the design and conduct of the study; in the collection, analysis
and interpretation of the data; or in the preparation, review and
approval of the manuscript.
NR 32
TC 11
Z9 11
U1 0
U2 0
PU CMA-CANADIAN MEDICAL ASSOC
PI OTTAWA
PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 5W8, CANADA
SN 0820-3946
EI 1488-2329
J9 CAN MED ASSOC J
JI Can. Med. Assoc. J.
PD DEC 14
PY 2010
VL 182
IS 18
BP 1953
EP 1958
DI 10.1503/cmaj.100374
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA 690JD
UT WOS:000284998700034
PM 21149533
ER
PT J
AU Edwards, LA
Fine, HA
AF Edwards, Lincoln A.
Fine, Howard A.
TI The Ids Have It
SO CANCER CELL
LA English
DT Editorial Material
ID TGF-BETA; LUNG METASTASIS; STEM-CELLS; CANCER; TUMORS
AB In this issue of Cancer Cell, Anido et al. demonstrate that Id1 is the likely arbiter of divergent transforming growth factor-beta (TGF-beta) signaling in glioma-initiating cells (GICs) from different tumors. These findings hold both the promise and potential peril of therapeutic targeting of the TGF-beta pathway.
C1 [Edwards, Lincoln A.; Fine, Howard A.] NINDS, Neurooncol Branch, NCI, NIH, Bethesda, MD 20892 USA.
RP Fine, HA (reprint author), NINDS, Neurooncol Branch, NCI, NIH, Bethesda, MD 20892 USA.
EM hfine@mail.nih.gov
NR 10
TC 1
Z9 4
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1535-6108
J9 CANCER CELL
JI Cancer Cell
PD DEC 14
PY 2010
VL 18
IS 6
BP 543
EP 545
DI 10.1016/j.ccr.2010.11.028
PG 3
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 697PL
UT WOS:000285527300004
PM 21156278
ER
PT J
AU Rui, LX
Emre, NCT
Kruhlak, MJ
Chung, HJ
Steidl, C
Slack, G
Wright, GW
Lenz, G
Ngo, VN
Shaffer, AL
Xu, WH
Zhao, H
Yang, YD
Lamy, L
Davis, RE
Xiao, WM
Powell, J
Maloney, D
Thomas, CJ
Moller, P
Rosenwald, A
Ott, G
Muller-Hermelink, HK
Savage, K
Connors, JM
Rimsza, LM
Campo, E
Jaffe, ES
Delabie, J
Smeland, EB
Weisenburger, DD
Chan, WC
Gascoyne, RD
Levens, D
Staudt, LM
AF Rui, Lixin
Emre, N. C. Tolga
Kruhlak, Michael J.
Chung, Hye-Jung
Steidl, Christian
Slack, Graham
Wright, George W.
Lenz, Georg
Ngo, Vu N.
Shaffer, Arthur L.
Xu, Weihong
Zhao, Hong
Yang, Yandan
Lamy, Laurence
Davis, R. Eric
Xiao, Wenming
Powell, John
Maloney, David
Thomas, Craig J.
Moeller, Peter
Rosenwald, Andreas
Ott, German
Muller-Hermelink, Hans Konrad
Savage, Kerry
Connors, Joseph M.
Rimsza, Lisa M.
Campo, Elias
Jaffe, Elaine S.
Delabie, Jan
Smeland, Erlend B.
Weisenburger, Dennis D.
Chan, Wing C.
Gascoyne, Randy D.
Levens, David
Staudt, Louis M.
TI Cooperative Epigenetic Modulation by Cancer Amplicon Genes
SO CANCER CELL
LA English
DT Article
ID B-CELL LYMPHOMA; CLASSICAL HODGKIN LYMPHOMA; REED-STERNBERG CELLS; EXON
12 MUTATIONS; HISTONE H3; JAK2 INHIBITOR; INTERLEUKIN-13 RECEPTOR;
MOLECULAR SIGNATURE; POLYCYTHEMIA-VERA; LYSINE 9
AB Chromosome band 9p24 is frequently amplified in primary mediastinal B cell lymphoma (PMBL) and Hodgkin lymphoma (HL). To identify oncogenes in this amplicon, we screened an RNA interference library targeting amplicon genes and thereby identified JAK2 and the histone demethylase JMJD2C as essential genes in these lymphomas. Inhibition of JAK2 and JMJD2C cooperated in killing these lymphomas by decreasing tyrosine 41 phosphorylation and increasing lysine 9 trimethylation of histone H3, promoting heterochromatin formation. MYC, a major target of JAK2-mediated histone phosphorylation, was silenced after JAK2 and JMJD2C inhibition, with a corresponding increase in repressive chromatin. Hence, JAK2 and JMJD2C cooperatively remodel the PMBL and HL epigenome, offering a mechanistic rationale for the development of JAK2 and JMJD2C inhibitors in these diseases.
C1 [Rui, Lixin; Emre, N. C. Tolga; Lenz, Georg; Ngo, Vu N.; Shaffer, Arthur L.; Xu, Weihong; Zhao, Hong; Yang, Yandan; Lamy, Laurence; Davis, R. Eric; Staudt, Louis M.] NCI, Metab Branch, Bethesda, MD 20892 USA.
[Kruhlak, Michael J.] NCI, Expt Immunol Branch, Bethesda, MD 20892 USA.
[Chung, Hye-Jung; Jaffe, Elaine S.; Levens, David] NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Steidl, Christian; Slack, Graham; Savage, Kerry; Connors, Joseph M.; Gascoyne, Randy D.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada.
[Wright, George W.] NCI, Biometr Res Branch, DCTD, NIH, Bethesda, MD 20892 USA.
[Xiao, Wenming; Powell, John] NIH, Bioinformat & Mol Anal Sect, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
[Maloney, David; Thomas, Craig J.] NHGRI, NIH Chem Genom Ctr, NIH, Rockville, MD 20850 USA.
[Moeller, Peter] Univ Ulm, Dept Pathol, D-89081 Ulm, Germany.
[Rosenwald, Andreas; Muller-Hermelink, Hans Konrad] Univ Wurzburg, Dept Pathol, D-97080 Wurzburg, Germany.
[Ott, German] Robert Bosch Krankenhaus, Dept Clin Pathol, D-70376 Stuttgart, Germany.
[Ott, German] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-70376 Stuttgart, Germany.
[Rimsza, Lisa M.] Univ Arizona, Dept Pathol, Tucson, AZ 85724 USA.
[Rimsza, Lisa M.] SW Oncol Grp, Ann Arbor, MI 48106 USA.
[Campo, Elias] Univ Barcelona, Hosp Clin, E-08036 Barcelona, Spain.
[Delabie, Jan] Oslo Univ Hosp, Pathol Clin, N-0027 Oslo, Norway.
[Smeland, Erlend B.] Oslo Univ Hosp, Inst Canc Res, N-0027 Oslo, Norway.
[Smeland, Erlend B.] Univ Oslo, Ctr Canc Biomed, N-0316 Oslo, Norway.
[Weisenburger, Dennis D.; Chan, Wing C.] Univ Nebraska, Dept Pathol, Omaha, NE 68198 USA.
[Weisenburger, Dennis D.; Chan, Wing C.] Univ Nebraska, Dept Microbiol, Omaha, NE 68198 USA.
RP Staudt, LM (reprint author), NCI, Metab Branch, Bethesda, MD 20892 USA.
EM lstaudt@mail.nih.gov
RI Lenz, Georg/I-6844-2012; Levens, David/C-9216-2009;
OI Levens, David/0000-0002-7616-922X; Campo, elias/0000-0001-9850-9793;
Delabie, Jan/0000-0001-5023-0689; Jaffe, Elaine/0000-0003-4632-0301
FU NIH, National Cancer Institute, Center for Cancer Research; NCI [UO1-CA
114778]; National Health and Medical Research Council (NHMRC) of
Australia; German Research Foundation (DFG); Cancer Research Society of
Canada; Terry Fox Foundation [019001]; Canadian Institutes for Health
[178536]
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research and an NCI
SPECS grant (UO1-CA 114778). L.R. is the recipient of a C.J. Martin
Fellowship from the National Health and Medical Research Council (NHMRC)
of Australia. G.L. was also supported by a research grant from the
German Research Foundation (DFG). C.S. is funded by a fellowship award
from the Cancer Research Society of Canada. R.D.G. is funded by a Terry
Fox Foundation award (019001) and a Canadian Institutes for Health
Research grant (178536). We thank Dennis Huszar of AstraZeneca for
providing AZD1480.
NR 54
TC 137
Z9 137
U1 2
U2 13
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1535-6108
J9 CANCER CELL
JI Cancer Cell
PD DEC 14
PY 2010
VL 18
IS 6
BP 590
EP 605
DI 10.1016/j.ccr.2010.11.013
PG 16
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 697PL
UT WOS:000285527300010
PM 21156283
ER
PT J
AU Olin, JW
Allie, DE
Belkin, M
Bonow, RO
Casey, DE
Creager, MA
Gerber, TC
Hirsch, AT
Jaff, MR
Kaufman, JA
Lewis, CA
Martin, ET
Martin, LG
Sheehan, P
Stewart, KJ
Treat-Jacobson, D
White, CJ
Zheng, ZJ
Masoudi, FA
DeLong, E
Erwin, JP
Goff, DC
Grady, K
Green, LA
Heidenreich, PA
Jenkins, KJ
Loth, AR
Peterson, ED
Shahian, DM
Brindis, RG
Lewin, JC
May, C
Shahriary, M
Chiu, JS
Barrett, EA
Brown, N
Robertson, RM
Whitman, GR
Randle, D
AF Olin, Jeffrey W.
Allie, David E.
Belkin, Michael
Bonow, Robert O.
Casey, Donald E., Jr.
Creager, Mark A.
Gerber, Thomas C.
Hirsch, Alan T.
Jaff, Michael R.
Kaufman, John A.
Lewis, Curtis A.
Martin, Edward T.
Martin, Louis G.
Sheehan, Peter
Stewart, Kerry J.
Treat-Jacobson, Diane
White, Christopher J.
Zheng, Zhi-Jie
Masoudi, Frederick A.
DeLong, Elizabeth
Erwin, John P., III
Goff, David C., Jr.
Grady, Kathleen
Green, Lee A.
Heidenreich, Paul A.
Jenkins, Kathy J.
Loth, Ann R.
Peterson, Eric D.
Shahian, David M.
Brindis, Ralph G.
Lewin, John C.
May, Charlene
Shahriary, Melanie
Chiu, Jensen S.
Barrett, Erin A.
Brown, Nancy
Robertson, Rose Marie
Whitman, Gayle R.
Randle, Dwight
CA Amer Coll Cardiology Fdn
Amer Heart Assoc Task Force Perfor
TI ACCF/AHA/ACR/SCAI/SIR/SVM/SVN/SVS 2010 Performance Measures for Adults
With Peripheral Artery Disease A Report of the American College of
Cardiology Foundation/American Heart Association Task Force on
Performance Measures, the American College of Radiology, the Society for
Cardiac Angiography and Interventions, the Society for Interventional
Radiology, the Society for Vascular Medicine, the Society for Vascular
Nursing, and the Society for Vascular Surgery (Writing Committee to
Develop Clinical Performance Measures for Peripheral Artery Disease)
SO CIRCULATION
LA English
DT Article
DE AHA Scientific Statements; abdominal aortic aneurysm; ankle brachial
index; peripheral arterial disease; secondary prevention; supervised
exercise
ID ABDOMINAL AORTIC-ANEURYSM; ANKLE-BRACHIAL INDEX;
REHABILITATION/SECONDARY PREVENTION SERVICES; ELEVATION
MYOCARDIAL-INFARCTION; CARDIOVASCULAR-DISEASE; INTERMITTENT
CLAUDICATION; GENERAL-POPULATION; CONTROLLED-TRIAL; ST-ELEVATION;
FOLLOW-UP
C1 [Zheng, Zhi-Jie] NHLBI, Bethesda, MD USA.
RI White, Christopher/J-6686-2012
OI White, Christopher/0000-0001-8618-7539
NR 73
TC 35
Z9 36
U1 1
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD DEC 14
PY 2010
VL 122
IS 24
BP 2583
EP 2618
DI 10.1161/CIR.0b013e3182031a3c
PG 36
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 693RN
UT WOS:000285243200018
PM 21126978
ER
PT J
AU Liu, LH
Das, S
Losert, W
Parent, CA
AF Liu, Lunhua
Das, Satarupa
Losert, Wolfgang
Parent, Carole A.
TI mTORC2 Regulates Neutrophil Chemotaxis in a cAMP- and RhoA-Dependent
Fashion
SO DEVELOPMENTAL CELL
LA English
DT Article
ID PROTEIN-KINASE-A; ADENYLYL-CYCLASE; CYCLIC-AMP; MEDIATED ACTIVATION;
CELL-MIGRATION; SIGNAL RELAY; CHEMOATTRACTANT RECEPTOR; PHOSPHORYLATION;
DICTYOSTELIUM; PATHWAY
AB We studied the role of the target of rapamycin complex 2 (mTORC2) during neutrophil chemotaxis, a process that is mediated through the polarization of actin and myosin filament networks. We show that inhibition of mTORC2 activity, achieved via knock down (KD) of Rictor, severely inhibits neutrophil polarization and directed migration induced by chemoattractants, independently of Akt. Rictor KD also abolishes the ability of chemoattractants to induce cAMP production, a process mediated through the activation of the adenylyl cyclase 9 (AC9). Cells with either reduced or higher AC9 levels also exhibit specific and severe tail retraction defects that are mediated through RhoA. We further show that cAMP is excluded from extending pseudopods and remains restricted to the cell body of migrating neutrophils. We propose that the mTORC2-dependent regulation of Myoll occurs through a cAMP/RhoA-signaling axis, independently of actin reorganization during neutrophil chemotaxis.
C1 [Liu, Lunhua; Das, Satarupa; Losert, Wolfgang; Parent, Carole A.] NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Losert, Wolfgang] Univ Maryland, Dept Phys, College Pk, MD 20742 USA.
RP Parent, CA (reprint author), NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA.
EM parentc@mail.nih.gov
OI Das, Satarupa/0000-0002-4217-9972
FU Center for Cancer Research, NCI, National Institutes of Health
FX We thank Drs. Daniel Storm for providing the cDNA encoding AC3 and AC9,
Henry Bourne for providing the PLB-985 cells, and Paul Randazzo for
providing the Rhotekin-sepharose beads and for helpful advice. We also
wish to thank the C.A.P. laboratory members for excellent discussions
and suggestions and for valuable input on the manuscript. A special
thanks goes to Dr. Valerie Barr for her help with the microscopy. W.L.
performed this work while on sabbatical at the LCMB, CCR. This research
was supported by the Intramural Research Program of the Center for
Cancer Research, NCI, National Institutes of Health.
NR 66
TC 88
Z9 92
U1 1
U2 4
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1534-5807
J9 DEV CELL
JI Dev. Cell
PD DEC 14
PY 2010
VL 19
IS 6
BP 845
EP 857
DI 10.1016/j.devcel.2010.11.004
PG 13
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 696OH
UT WOS:000285450200010
PM 21145500
ER
EF