FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Soubias, O
Kimura, T
Teague, WE
Hines, KG
Yeliseev, AA
Gawrisch, K
AF Soubias, Olivier
Kimura, Tomohiro
Teague, Walter E., Jr.
Hines, Kirk G.
Yeliseev, Alexei A.
Gawrisch, Klaus
TI Lipid interaction with G protein-coupled membrane receptors studied by
NMR
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 247th National Spring Meeting of the American-Chemical-Society (ACS)
CY MAR 16-20, 2014
CL Dallas, TX
SP Amer Chem Soc
C1 [Soubias, Olivier; Kimura, Tomohiro; Teague, Walter E., Jr.; Hines, Kirk G.; Yeliseev, Alexei A.; Gawrisch, Klaus] NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA.
EM gawrisch@helix.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 16
PY 2014
VL 247
MA 568-COLL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ8HD
UT WOS:000348455204310
ER
PT J
AU Tarasova, OA
Urusova, AF
Zakharov, AV
Filimonov, DA
Poroikov, VV
AF Tarasova, Olga A.
Urusova, Alexandra F.
Zakharov, Alexey V.
Filimonov, Dmitry A.
Poroikov, Vladimir V.
TI Combining QSAR-analysis and fragment-based drug design in search for new
anti-HIV agents
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 247th National Spring Meeting of the American-Chemical-Society (ACS)
CY MAR 16-20, 2014
CL Dallas, TX
SP Amer Chem Soc
C1 [Tarasova, Olga A.; Urusova, Alexandra F.; Filimonov, Dmitry A.; Poroikov, Vladimir V.] Russian Acad Med Sci, Orekhovich Inst Biomed Chem, Dept Bioinformat, Moscow, Russia.
[Zakharov, Alexey V.] NCI, Ctr Canc Res, NIH, Frederick, MD 21701 USA.
EM olga.a.tarasova@gmail.com; vladimir.poroikov@ibmc.msk.ru
RI Tarasova, Olga/E-4318-2014
OI Tarasova, Olga/0000-0002-4230-3849
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 16
PY 2014
VL 247
MA 35-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ8HD
UT WOS:000348455204606
ER
PT J
AU Thiessen, P
Yu, B
Fu, G
Bolton, E
AF Thiessen, Paul
Yu, Bo
Fu, Gang
Bolton, Evan
TI PubChem in the cloud
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 247th National Spring Meeting of the American-Chemical-Society (ACS)
CY MAR 16-20, 2014
CL Dallas, TX
SP Amer Chem Soc
C1 [Thiessen, Paul; Yu, Bo; Fu, Gang; Bolton, Evan] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
EM bolton@ncbi.nlm.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 16
PY 2014
VL 247
MA 62-CINF
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ8HD
UT WOS:000348455203653
ER
PT J
AU Zakharov, AV
Nicklaus, MC
AF Zakharov, Alexey V.
Nicklaus, Marc C.
TI QSAR modelling of rodent acute toxicity
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 247th National Spring Meeting of the American-Chemical-Society (ACS)
CY MAR 16-20, 2014
CL Dallas, TX
SP Amer Chem Soc
C1 [Zakharov, Alexey V.; Nicklaus, Marc C.] NCI, US Dept HHS, NIH, Frederick, MD 21702 USA.
EM alexey.zakharov@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 16
PY 2014
VL 247
MA 304-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ8HD
UT WOS:000348455204846
ER
PT J
AU Liu, ZH
Vong, QP
Liu, CY
Zheng, YX
AF Liu, Zhonghua
Vong, Queenie P.
Liu, Chengyu
Zheng, Yixian
TI Borg5 is required for angiogenesis by regulating persistent directional
migration of the cardiac microvascular endothelial cells
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID MOLECULAR-MECHANISMS; FIBROBLAST MIGRATION; MYOSIN-II; IN-VITRO; SEPTIN;
CDC42; CYTOSKELETON; PROTEINS; FAMILY; MORPHOGENESIS
AB The microvasculature is important for vertebrate organ development and homeostasis. However, the molecular mechanism of microvascular angiogenesis remains incompletely understood. Through studying Borg5 (Binder of the Rho GTPase 5), which belongs to a family of poorly understood effector proteins of the Cdc42 GTPase, we uncover a role for Borg5 in microvascular angiogenesis. Deletion of Borg5 in mice results in defects in retinal and cardiac microvasculature as well as heart development. Borg5 promotes angiogenesis by regulating persistent directional migration of the endothelial cells (ECs). In primary mouse cardiac ECs (MCECs), Borg5 associates with septins in the perinuclear region and colocalizes with actomyosin fibers. Both Borg5 deletion and septin 7 knockdown lead to a disruption of the perinuclear actomyosin and persistent directional migration. Our findings suggest that Borg5 and septin cytoskeleton spatially control actomyosin activity to ensure persistent directional migration of MCECs and efficient microvascular angiogenesis. Our studies reported here should offer a new avenue to further investigate the functions of Borg5, septin, and actomyosin in the microvasculature in the context of development and disease.
C1 [Liu, Zhonghua; Vong, Queenie P.; Zheng, Yixian] Carnegie Inst Sci, Dept Embryol, Baltimore, MD 21218 USA.
[Liu, Chengyu] NHLBI, iPSC, Bethesda, MD 20892 USA.
[Liu, Chengyu] NHLBI, Genome Engn Core, NIH, Bethesda, MD 20892 USA.
RP Zheng, YX (reprint author), Carnegie Inst Sci, Dept Embryol, Baltimore, MD 21218 USA.
EM zheng@ciwemb.edu
FU National Heart, Lung, and Blood Institute [R01 GM056312]; Howard Hughes
Medical Institute
FX We thank Ona Martin, Rong Chen, and Xiaohong Ma for technical support;
Youngjo Kim for designing the Borg5 knockout screening primers; Elias T.
Spiliotis for advice on septin antibodies; and Chen-Ming Fan and members
of the Zheng lab for helpful comments. The research was supported by
National Heart, Lung, and Blood Institute intramural research (C.L.),
R01 GM056312, and the Howard Hughes Medical Institute (Q.P.V., Z.L., and
Y.Z.).
NR 38
TC 4
Z9 4
U1 0
U2 2
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
EI 1939-4586
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD MAR 15
PY 2014
VL 25
IS 6
BP 841
EP 851
DI 10.1091/mbc.E13-09-0543
PG 11
WC Cell Biology
SC Cell Biology
GA AM1SX
UT WOS:000339629700017
PM 24451259
ER
PT J
AU Sakai, H
Fujigaki, H
Mazur, SJ
Appella, E
AF Sakai, Hiroyasu
Fujigaki, Hidetsugu
Mazur, Sharlyn J.
Appella, Ettore
TI Wild-type p53-induced phosphatase 1 (Wip1) forestalls cellular premature
senescence at physiological oxygen levels by regulating DNA damage
response signaling during DNA replication
SO CELL CYCLE
LA English
DT Article
DE Wip1; p53; cellular senescence; DNA damage response; ATM; camptothecin
ID DOUBLE-STRAND BREAKS; P53 TUMOR-SUPPRESSOR; OXIDATIVE STRESS; IN-VIVO;
DOWN-REGULATION; PROTEIN PHOSPHATASE; IONIZING-RADIATION; GENOME
MAINTENANCE; HUMAN FIBROBLASTS; ATM ACTIVATION
AB Wip1 (protein phosphatase Mg2+/Mn2+-dependent 1D, Ppm1d) is a nuclear serine/threonine protein phosphatase that is induced by p53 following the activation of DNA damage response (DDR) signaling. Ppm1d(-/-) mouse embryonic fibroblasts (MEFs) exhibit premature senescence under conventional culture conditions; however, little is known regarding the role of Wip1 in regulating cellular senescence. In this study, we found that even at a representative physiological concentration of 3% O-2, Ppm1d(-/-) MEFs underwent premature cellular senescence that depended on the functional activation of p53. Interestingly, Ppm1d(-/-) MEFs showed increased H2AX phosphorylation levels without increased levels of reactive oxygen species (ROS) or DNA base damage compared with wild-type (Wt) MEFs, suggesting a decreased threshold for DDR activation or sustained DDR activation during recovery. Notably, the increased H2AX phosphorylation levels observed in Ppm1d(-/-) MEFs were primarily associated with S-phase cells and predominantly dependent on the activation of ATM. Moreover, these same phenotypes were observed when Wt and Ppm1d(-/-) MEFs were either transiently or chronically exposed to low levels of agents that induce replication-mediated double-stranded breaks. These findings suggest that Wip1 prevents the induction of cellular senescence at physiological oxygen levels by attenuating DDR signaling in response to endogenous double-stranded breaks that form during DNA replication.
C1 [Sakai, Hiroyasu; Fujigaki, Hidetsugu; Mazur, Sharlyn J.; Appella, Ettore] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Appella, E (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA.
EM appellae@pop.nci.nih.gov
FU Center for Canter Research, National Cancer Institute, National
Institutes of Health
FX This research was supported by the Intramural Research Program of the
Center for Canter Research, National Cancer Institute, National
Institutes of Health.
NR 91
TC 6
Z9 7
U1 1
U2 10
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
EI 1551-4005
J9 CELL CYCLE
JI Cell Cycle
PD MAR 15
PY 2014
VL 13
IS 6
BP 1015
EP 1029
DI 10.4161/cc.27920
PG 15
WC Cell Biology
SC Cell Biology
GA AI2AT
UT WOS:000336659200022
PM 24552809
ER
PT J
AU Maciejewski, M
Barlow, PN
Tjandra, N
AF Maciejewski, Mateusz
Barlow, Paul N.
Tjandra, Nico
TI Decoding the Components of Dynamics in Three-Domain Proteins
SO JOURNAL OF COMPUTATIONAL CHEMISTRY
LA English
DT Article
DE protein dynamics; interdomain dynamics; protein function; nuclear
magnetic resonance; protein structure
ID MODEL-FREE APPROACH; NUCLEAR-MAGNETIC-RESONANCE; BODY STOCHASTIC
APPROACH; NMR RELAXATION; MULTIDOMAIN PROTEINS; INTERDOMAIN MOBILITY;
ROTATIONAL MOTIONS; BROWNIAN DYNAMICS; SPIN RELAXATION; DOMAIN MOTIONS
AB In this study, we examine the feasibility and limitations of describing the motional behavior of three-domain proteins in which the domains are linearly connected. In addition to attempting the determination of the internal and overall reorientational correlation times, we investigate the existence of correlations in the motions between the three domains. Since in linearly arranged three-domain proteins, there are typically no experimental data that can directly report on motional correlation between the first and the third domain, we address this question by dynamics simulations. Two limiting cases occur: (1) for weak repulsive potentials and (2) when strong repulsive potentials are applied between sequential domains. The motions of the terminal domains become correlated in the case of strong interdomain repulsive potentials when these potentials do not allow the angle between the sequential domains to be smaller than about 60 degrees. Using the model-free (MF) and extended MF formalisms of Lipari and Szabo, we find that the motional behavior can be separated into two components; the first component represents the concerted overall motion of the three domains, and the second describes the independent component of the motion of each individual domain. We find that this division of the motional behavior of the protein is maintained only when their timescales are distinct and can be made when the angles between sequential domains remain between 60 degrees and 160 degrees. In this work, we identify and quantify interdomain motional correlations. (c) 2013 Wiley Periodicals, Inc.
C1 [Maciejewski, Mateusz] Novartis Inst Biomed Res, Ctr Prote Chem, Cambridge, MA 02139 USA.
[Barlow, Paul N.] Univ Edinburgh, Sch Chem, Edinburgh EH9 3JJ, Midlothian, Scotland.
[Tjandra, Nico] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA.
RP Maciejewski, M (reprint author), Novartis Inst Biomed Res, Ctr Prote Chem, 250 Massachusetts Ave, Cambridge, MA 02139 USA.
EM paul.barlow@ed.ac.uk; tjandran@nhlbi.nih.gov
FU Intramural Research Program of the NIH, NHLBI; Wellcome Trust/NIH PhD
Studentship
FX Contract grant sponsor: Intramural Research Program of the NIH, NHLBI
(to N.T.); Contract grant sponsor: Wellcome Trust/NIH PhD Studentship(to
M. M.)
NR 38
TC 2
Z9 2
U1 1
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0192-8651
EI 1096-987X
J9 J COMPUT CHEM
JI J. Comput. Chem.
PD MAR 15
PY 2014
VL 35
IS 7
BP 518
EP 525
DI 10.1002/jcc.23510
PG 8
WC Chemistry, Multidisciplinary
SC Chemistry
GA AE9ME
UT WOS:000334331100002
PM 24323885
ER
PT J
AU Leeman-Neill, RJ
Kelly, LM
Liu, PY
Brenner, AV
Little, MP
Bogdanova, TI
Evdokimova, VN
Hatch, M
Zurnadzy, LY
Nikiforova, MN
Yue, NJ
Zhang, M
Mabuchi, K
Tronko, MD
Nikiforov, YE
AF Leeman-Neill, Rebecca J.
Kelly, Lindsey M.
Liu, Pengyuan
Brenner, Alina V.
Little, Mark P.
Bogdanova, Tetiana I.
Evdokimova, Viktoria N.
Hatch, Maureen
Zurnadzy, Liudmyla Y.
Nikiforova, Marina N.
Yue, Ning J.
Zhang, Miao
Mabuchi, Kiyohiko
Tronko, Mykola D.
Nikiforov, Yuri E.
TI ETV6-NTRK3 Is a Common Chromosomal Rearrangement in Radiation-Associated
Thyroid Cancer
SO CANCER
LA English
DT Article
DE thyroid cancer; radiation; chromosomal rearrangements; NTRK3; Chernobyl
ID ATOMIC-BOMB SURVIVORS; POST-CHERNOBYL; GENE FUSION; EXTERNAL RADIATION;
ACCIDENT; UKRAINE; CHILDREN; LEUKEMIA; DISEASES; COHORT
AB BACKGROUNDIn their previous analysis of papillary thyroid carcinomas (PTCs) from an Ukrainian-American cohort that was exposed to iodine-131 (I-131) from the Chernobyl accident, the authors identified RET/PTC rearrangements and other driver mutations in 60% of tumors.
METHODSIn this study, the remaining mutation-negative tumors from that cohort were analyzed using RNA sequencing (RNA-Seq) and reverse transcriptase-polymerase chain reaction to identify novel chromosomal rearrangements and to characterize their relation with radiation dose.
RESULTSThe ETS variant gene 6 (ETV6)-neurotrophin receptor 3 (NTRK3) rearrangement (ETV6-NTRK3) was identified by RNA-Seq in a tumor from a patient who received a high I-131 dose. Overall, the rearrangement was detected in 9 of 62 (14.5%) post-Chernobyl PTCs and in 3 of 151 (2%) sporadic PTCs (P=.019). The most common fusion type was between exon 4 of ETV6 and exon 14 of NTRK3. The prevalence of ETV6-NTRK3 rearrangement in post-Chernobyl PTCs was associated with increasing I-131 dose, albeit at borderline significance (P=.126). The group of rearrangement-positive PTCs (ETV6-NTRK3, RET/PTC, PAX8-PPAR) was associated with significantly higher dose response compared with the group of PTCs with point mutations (BRAF, RAS; P<.001). In vitro exposure of human thyroid cells to 1 gray of I-131 and -radiation resulted in the formation of ETV6-NTRK3 rearrangement at a rate of 7.9x10(-6) cells and 3.0x10(-6) cells, respectively.
CONCLUSIONSThe authors report the occurrence of ETV6-NTRK3 rearrangements in thyroid cancer and demonstrate that this rearrangement is significantly more common in tumors associated with exposure to I-131 and has a borderline significant dose response. Moreover, ETV6-NTRK3 rearrangement can be directly induced in thyroid cells by ionizing radiation in vitro and, thus, may represent a novel mechanism of radiation-induced carcinogenesis. Cancer 2014;120:799-807. (c) 2013 American Cancer Society.
The occurrence of ETV6-NTRK3 rearrangements in thyroid cancer is analyzed, and the results indicate that these rearrangements are significantly more common in tumors associated with exposure to iodine-131. Moreover, the findings demonstrate that ETV6-NTRK3 rearrangements can be induced in thyroid cells by ionizing radiation in vitro, and this is likely to serve as a novel mechanism of radiation-induced carcinogenesis.
C1 [Leeman-Neill, Rebecca J.; Kelly, Lindsey M.; Evdokimova, Viktoria N.; Nikiforova, Marina N.; Nikiforov, Yuri E.] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA.
[Liu, Pengyuan] Med Coll Wisconsin, Dept Physiol, Milwaukee, WI 53226 USA.
[Liu, Pengyuan] Med Coll Wisconsin, Ctr Canc, Milwaukee, WI 53226 USA.
[Brenner, Alina V.; Little, Mark P.; Hatch, Maureen; Mabuchi, Kiyohiko] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Bogdanova, Tetiana I.; Zurnadzy, Liudmyla Y.; Tronko, Mykola D.] Ukraine Acad Med Sci, State Inst P Komisarenko Inst Endocrinol & Metab, Kiev, Ukraine.
[Yue, Ning J.; Zhang, Miao] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Radiat Oncol, Canc Inst New Jersey, New Brunswick, NJ USA.
RP Nikiforov, YE (reprint author), Univ Pittsburgh, Dept Pathol, Clinical Lab Bldg,Room 8031,3477 Euler Way, Pittsburgh, PA 15213 USA.
EM nikiforovye@upmc.edu
OI Little, Mark/0000-0003-0980-7567
FU National Institutes of Health (NIH) [R01 CA88041]; Intramural Research
Program of the NIH, National Cancer Institute
FX This work was supported by National Institutes of Health (NIH) grant R01
CA88041 and in part by the Intramural Research Program of the NIH,
National Cancer Institute.
NR 42
TC 42
Z9 46
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
EI 1097-0142
J9 CANCER-AM CANCER SOC
JI Cancer
PD MAR 15
PY 2014
VL 120
IS 6
BP 799
EP 807
DI 10.1002/cncr.28484
PG 9
WC Oncology
SC Oncology
GA AB9UB
UT WOS:000332140100007
PM 24327398
ER
PT J
AU Langford, AT
Resnicow, K
Dimond, EP
Denicoff, AM
St Germain, D
McCaskill-Stevens, W
Enos, RA
Carrigan, A
Wilkinson, K
Go, RS
AF Langford, Aisha T.
Resnicow, Ken
Dimond, Eileen P.
Denicoff, Andrea M.
St. Germain, Diane
McCaskill-Stevens, Worta
Enos, Rebecca A.
Carrigan, Angela
Wilkinson, Kathy
Go, Ronald S.
TI Racial/Ethnic Differences in Clinical Trial Enrollment, Refusal Rates,
Ineligibility, and Reasons for Decline Among Patients at Sites in the
National Cancer Institute's Community Cancer Centers Program
SO CANCER
LA English
DT Article
DE racial; ethnic; African Americans; Hispanic; minorities; clinical
trials; medical research; cancer
ID PARTICIPATION; DISPARITIES; BARRIERS; AGE
AB BACKGROUNDThis study examined racial/ethnic differences among patients in clinical trial (CT) enrollment, refusal rates, ineligibility, and desire to participate in research within the National Cancer Institute's Community Cancer Centers Program (NCCCP) Clinical Trial Screening and Accrual Log.
METHODSData from 4509 log entries were evaluated in this study. Four logistic regression models were run using physical/medical conditions, enrollment into a CT, patient eligible but declined a CT, and no desire to participate in research as dependent variables.
RESULTSAge65 years (OR=1.51, 95% CI=1.28-1.79), males (OR=2.28, 95% CI=1.92-2.71), and non-Hispanic black race (OR=1.53, 95% CI=1.2-1.96) were significantly associated with more physical/medical conditions. Age65 years was significantly associated with lower CT enrollment (OR=0.83, 95% CI=0.7-0.98). Males (OR=0.78, 95% CI=0.65-0.94) and a higher grade level score for consent form readability (OR=0.9, 95% CI=0.83-0.97) were significantly associated with lower refusal rates. Consent page length20 was significantly associated with lower odds of no desire to participate in research among CT decliners (OR=0.75, 95% CI=0.58-0.98).
CONCLUSIONSThere were no racial/ethnic differences in CT enrollment, refusal rates, or no desire to participate in research as the reason given for CT refusal. Higher odds of physical/medical conditions were associated with older age, males, and non-Hispanic blacks. Better management of physical/medical conditions before and during treatment may increase the pool of eligible patients for CTs. Future work should examine the role of comorbidities, sex, age, and consent form characteristics on CT participation. Cancer 2014;120:877-884. (c) 2013 American Cancer Society.
There were no racial/ethnic differences in clinical trial (CT) enrollment, refusal rates, or no desire to participate in research as the reason given for CT refusal; however, higher odds of physical/medical conditions were associated with older age, males, and non-Hispanic blacks. Better management of physical/medical conditions before and during treatment may increase the pool of eligible patients for CTs.
C1 [Langford, Aisha T.; Resnicow, Ken] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA.
[Dimond, Eileen P.; St. Germain, Diane; McCaskill-Stevens, Worta] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Denicoff, Andrea M.] NCI, Canc Therapy Evaluat Program, Bethesda, MD USA.
[Enos, Rebecca A.] EMMES Corp, Rockville, MD USA.
[Carrigan, Angela] SAIC Frederick Inc, Clin Res Directorate CMRP, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Wilkinson, Kathy] Billings Clin Canc Ctr, Billings, MT USA.
[Go, Ronald S.] Gundersen Hlth Syst, La Crosse, WI USA.
RP Langford, AT (reprint author), Univ Michigan, Sch Publ Hlth, 1415 Washington Hts, Ann Arbor, MI 48109 USA.
EM alangfor@umich.edu
OI Langford, Aisha/0000-0003-1758-691X
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX This project has been funded in whole or in part with Federal funds from
the National Cancer Institute, National Institutes of Health, under
Contract No. HHSN261200800001E. The content of this publication does not
necessarily reflect the views of policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the US Government.
NR 27
TC 18
Z9 18
U1 2
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
EI 1097-0142
J9 CANCER-AM CANCER SOC
JI Cancer
PD MAR 15
PY 2014
VL 120
IS 6
BP 877
EP 884
DI 10.1002/cncr.28483
PG 8
WC Oncology
SC Oncology
GA AB9UB
UT WOS:000332140100016
PM 24327389
ER
PT J
AU Bates, SE
AF Bates, Susan E.
TI It's All About the Test: The Complexity of Companion Diagnostic
Co-development in Personalized Medicine
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 0
TC 1
Z9 1
U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAR 15
PY 2014
VL 20
IS 6
BP 1418
EP 1418
DI 10.1158/1078-0432.CCR-14-0223
PG 1
WC Oncology
SC Oncology
GA AE2ON
UT WOS:000333812700004
PM 24634464
ER
PT J
AU Rubin, EH
Allen, JD
Nowak, JA
Bates, SE
AF Rubin, Eric H.
Allen, Jeffrey D.
Nowak, Jan A.
Bates, Susan E.
TI Developing Precision Medicine in a Global World
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID L265P SOMATIC MUTATION; CELL LUNG-CANCER; MYD88 L265P; COMPANION
DIAGNOSTICS; WALDENSTROM MACROGLOBULINEMIA; BREAST-CANCER;
CLINICAL-ONCOLOGY; AMERICAN-SOCIETY; EUROPEAN-UNION; PRIME-TIME
AB Advances in understanding the biology of cancer, as well as advances in diagnostic technologies, such as the advent of affordable high-resolution DNA sequencing, have had a major impact on the approach to identification of specific alterations in a given patient's cancer that could be used as a basis for treatment selection, and hence the development of companion diagnostics. Although there are now several examples of successful development of companion diagnostics that allow identification of patients who will achieve the greatest benefit from a new therapeutic, the path to coapproval of a diagnostic test along with a new therapeutic is complex and often inefficient. This review and the accompanying articles examine the current state of companion diagnostic development in the United States and Europe from academic, industry, regulatory, and economic perspectives. See all articles in this CCR Focus section, "The Precision Medicine Conundrum: Approaches to Companion Diagnostic Co-development." (C)2014 AACR.
C1 [Rubin, Eric H.] Merck Res Labs, N Wales, PA 19454 USA.
[Allen, Jeffrey D.] Friends Canc Res, Arlington, VA USA.
[Nowak, Jan A.] NorthShore Univ Hlth Syst Pathol & Lab Med, Evanston, IL USA.
[Bates, Susan E.] NCI, Dev Therapeut Branch, Bethesda, MD 20892 USA.
RP Rubin, EH (reprint author), Merck Res Labs, 351 North Sumneytown Pike, N Wales, PA 19454 USA.
EM eric_rubin@merck.com
NR 32
TC 19
Z9 20
U1 1
U2 17
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAR 15
PY 2014
VL 20
IS 6
BP 1419
EP 1427
DI 10.1158/1078-0432.CCR-14-0091
PG 9
WC Oncology
SC Oncology
GA AE2ON
UT WOS:000333812700005
PM 24634465
ER
PT J
AU Parkinson, DR
McCormack, RT
Keating, SM
Gutman, SI
Hamilton, SR
Mansfield, EA
Piper, MA
DeVerka, P
Frueh, FW
Jessup, JM
McShane, LM
Tunis, SR
Sigman, CC
Kelloff, GJ
AF Parkinson, David R.
McCormack, Robert T.
Keating, Susan M.
Gutman, Steven I.
Hamilton, Stanley R.
Mansfield, Elizabeth A.
Piper, Margaret A.
DeVerka, Patricia
Frueh, Felix W.
Jessup, J. Milburn
McShane, Lisa M.
Tunis, Sean R.
Sigman, Caroline C.
Kelloff, Gary J.
TI Evidence of Clinical Utility: An Unmet Need in Molecular Diagnostics for
Patients with Cancer
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID CELL LUNG-CANCER; PATHOLOGISTS GUIDELINE RECOMMENDATIONS; OMICS-BASED
PREDICTORS; BREAST-CANCER; COLORECTAL-CANCER; AMERICAN-SOCIETY; DRUG
DEVELOPMENT; TRIAL DESIGNS; TUMOR-MARKERS; BIOMARKERS
AB This article defines and describes best practices for the academic and business community to generate evidence of clinical utility for cancer molecular diagnostic assays. Beyond analytical and clinical validation, successful demonstration of clinical utility involves developing sufficient evidence to demonstrate that a diagnostic test results in an improvement in patient outcomes. This discussionis complementary to theoretical frameworks described in previously published guidance and literature reports by the U. S. Food and Drug Administration, Centers for Disease Control and Prevention, Institute of Medicine, and Center for Medical Technology Policy, among others. These reports are comprehensive and specifically clarify appropriate clinical use, adoption, and payer reimbursement for assay manufacturers, as well as Clinical Laboratory Improvement Amendments-certified laboratories, including those that develop assays (laboratory developed tests). Practical criteria and steps for establishing clinical utility are crucial to subsequent decisions for reimbursement without which high-performing molecular diagnostics will have limited availability to patients with cancer and fail to translate scientific advances into high-quality and cost-effective cancer care. See all articles in this CCR Focus section, "The Precision Medicine Conundrum: Approaches to Companion Diagnostic Co-development." (C)2014 AACR.
C1 [Parkinson, David R.] New Enterprise Associates Inc, Menlo Pk, CA USA.
[Keating, Susan M.; Sigman, Caroline C.] CCS Associates, Mountain View, CA USA.
[Gutman, Steven I.] Myraqa, Redwood Shores, CA USA.
[McCormack, Robert T.] Johnson & Johnson Veridex LLC, Raritan, NJ USA.
[Hamilton, Stanley R.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Mansfield, Elizabeth A.] Off In Vitro Diagnost, Personalized Med Program, Ctr Diagnost & Radiol Hlth, Silver Spring, MD USA.
[DeVerka, Patricia; Tunis, Sean R.] Ctr Med Technol Policy, Baltimore, MD USA.
[Frueh, Felix W.] Opus Three LLC, Rockville, MD USA.
[Jessup, J. Milburn; McShane, Lisa M.; Kelloff, Gary J.] NCI, Div Canc Treatment & Diag, Rockville, MD USA.
[Piper, Margaret A.] Kaiser Permanente Ctr Hlth Res, Kaiser Permanente Res, Evidence Based Practice Ctr, Portland, OR USA.
RP Parkinson, DR (reprint author), New Enterprise Associates, Menlo Pk, CA 94025 USA.
EM dparkinson@nea.com
FU National Institutes of Health Biomarkers Consortium
FX The authors wish to gratefully acknowledge the support of the Foundation
for the National Institutes of Health Biomarkers Consortium in providing
a venue for carrying out this project.
NR 97
TC 31
Z9 31
U1 0
U2 14
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAR 15
PY 2014
VL 20
IS 6
BP 1428
EP 1444
DI 10.1158/1078-0432.CCR-13-2961
PG 17
WC Oncology
SC Oncology
GA AE2ON
UT WOS:000333812700006
PM 24634466
ER
PT J
AU Knowles, MR
Ostrowski, LE
Leigh, MW
Sears, PR
Davis, SD
Wolf, WE
Hazucha, MJ
Carson, JL
Olivier, KN
Sagel, SD
Rosenfeld, M
Ferkol, TW
Dell, SD
Milla, CE
Randell, SH
Yin, WN
Sannuti, A
Metjian, HM
Noone, PG
Noone, PJ
Olson, CA
Patrone, MV
Dang, H
Lee, HS
Hurd, TW
Gee, HY
Otto, EA
Halbritter, J
Kohl, S
Kircher, M
Krischer, J
Bamshad, MJ
Nickerson, DA
Hildebrandt, F
Shendure, J
Zariwala, MA
AF Knowles, Michael R.
Ostrowski, Lawrence E.
Leigh, Margaret W.
Sears, Patrick R.
Davis, Stephanie D.
Wolf, Whitney E.
Hazucha, Milan J.
Carson, Johnny L.
Olivier, Kenneth N.
Sagel, Scott D.
Rosenfeld, Margaret
Ferkol, Thomas W.
Dell, Sharon D.
Milla, Carlos E.
Randell, Scott H.
Yin, Weining
Sannuti, Aruna
Metjian, Hilda M.
Noone, Peadar G.
Noone, Peter J.
Olson, Christina A.
Patrone, Michael V.
Dang, Hong
Lee, Hye-Seung
Hurd, Toby W.
Gee, Heon Yung
Otto, Edgar A.
Halbritter, Jan
Kohl, Stefan
Kircher, Martin
Krischer, Jeffrey
Bamshad, Michael J.
Nickerson, Deborah A.
Hildebrandt, Friedhelm
Shendure, Jay
Zariwala, Maimoona A.
TI Mutations in RSPH1 Cause Primary Ciliary Dyskinesia with a Unique
Clinical and Ciliary Phenotype
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
DE cilia; Kartagener syndrome; ciliopathy; exome sequencing; RSPH1
ID OF-FUNCTION MUTATIONS; INNER DYNEIN ARMS; REGULATORY COMPLEX; BODY
ASYMMETRY; OUTER; DEFECTS; RANDOMIZATION; HUMANS; MOTILITY; ZMYND10
AB Rationale: Primary ciliary dyskinesia (PCD) is a genetically heterogeneous recessive disorder of motile cilia, but the genetic cause is not defined for all patients with PCD.
Objectives: To identify disease-causing mutations in novel genes, we performed exome sequencing, follow-up characterization, mutation scanning, and genotype-phenotype studies in patients with PCD.
Methods: Whole-exome sequencing was performed using NimbleGen capture and Illumina HiSeq sequencing. Sanger-based sequencing was used for mutation scanning, validation, and segregation analysis.
Measurements and Main Results: We performed exome sequencing on an affected sib-pair with normal ultrastructure in more than 85% of cilia. A homozygous splice-site mutation was detected in RSPH1 in both siblings; parents were carriers. Screening RSPH1 in 413 unrelated probands, including 325 with PCD and 88 with idiopathic bronchiectasis, revealed biallelic loss-of-function mutations in nine additional probands. Five affected siblings of probands in RSPH1 families harbored the familial mutations. The 16 individuals with RSPH1 mutations had some features of PCD; however, nasal nitric oxide levels were higher than in patients with PCD with other gene mutations (98.3 vs. 20.7 nl/min; P < 0.0003). Additionally, individuals with RSPH1 mutations had a lower prevalence (8 of 16) of neonatal respiratory distress, and later onset of daily wet cough than typical for PCD, and better lung function (FEU, compared with 75 age- and sex-matched PCD cases (73.0 vs 61.8, FEV1% predicted; P = 0.043). Cilia from individuals with RSPH1 mutations had normal beat frequency (6.1 +/- Hz at 25 degrees C), but an abnormal, circular beat pattern.
Conclusions: The milder clinical disease and higher nasal nitric oxide in individuals with biallelic imitations in RSPH1 provides evidence of a unique genotype-phenotype relationship in PCD, and suggests that mutations in RSPH1 may be associated with residual ciliary function.
C1 [Knowles, Michael R.; Ostrowski, Lawrence E.; Sears, Patrick R.; Wolf, Whitney E.; Hazucha, Milan J.; Yin, Weining; Sannuti, Aruna; Metjian, Hilda M.; Noone, Peadar G.; Noone, Peter J.; Olson, Christina A.; Patrone, Michael V.; Dang, Hong] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA.
[Leigh, Margaret W.; Davis, Stephanie D.; Carson, Johnny L.] Univ N Carolina, Sch Med, Dept Pediat, Chapel Hill, NC USA.
[Randell, Scott H.] Univ N Carolina, Sch Med, Dept Cell Biol & Physiol, Chapel Hill, NC USA.
[Zariwala, Maimoona A.] Univ N Carolina, Sch Med, Dept Pathol & Lab Med, Chapel Hill, NC USA.
[Olivier, Kenneth N.] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA.
[Sagel, Scott D.] Univ Colorado, Dept Pediat, Sch Med, Aurora, CO USA.
[Rosenfeld, Margaret] Univ Washington, Sch Med, Seattle Childrens Hosp, Seattle, WA USA.
[Rosenfeld, Margaret; Bamshad, Michael J.] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA.
[Kircher, Martin; Bamshad, Michael J.; Nickerson, Deborah A.; Shendure, Jay] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA USA.
[Ferkol, Thomas W.] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA.
[Dell, Sharon D.] Univ Toronto, Hosp Sick Children, Dept Pediat, Toronto, ON M5G 1X8, Canada.
[Milla, Carlos E.] Stanford Univ, Dept Pediat, Palo Alto, CA 94304 USA.
[Metjian, Hilda M.] Raleigh Pulm & Allergy, Raleigh, NC USA.
[Lee, Hye-Seung; Krischer, Jeffrey] Univ S Florida, Dept Pediat, Tampa, FL 33620 USA.
[Hurd, Toby W.; Gee, Heon Yung; Otto, Edgar A.; Halbritter, Jan; Kohl, Stefan; Hildebrandt, Friedhelm] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA.
[Hildebrandt, Friedhelm] Howard Hughes Med Inst, Chevy Chase, MD USA.
RP Knowles, MR (reprint author), Cyst Fibrosis Ctr, 7019 Thurston Bowles Bldg,CB7248, Chapel Hill, NC 27599 USA.
EM knowles@med.unc.edu; zariwala@med.unc.edu
OI Otto, Edgar/0000-0002-2387-9973; Kircher, Martin/0000-0001-9278-5471
FU NIH-ORDR-NHLBI [U54HL096458-06]; NIH-NHLBI [5R01HL071798, 1R01HL117836,
HHSN268201100037C.]; NIH-NHGRI [U54HG006493]; NIH-R01 [DK068306];
Intramural Research Program of the NIH-NIAID; NIH-NCATS [UL1TR000083];
Chapel Hill [UL1TR000154]; Cystic Fibrosis Foundation [CFF R026-CRO7,
R026-CR11]; NIH-NIDDK [P30-DK065988]
FX Supported by NIH-ORDR-NHLBI grant 5 U54HL096458-06 (M.R.K., M.W.L.,
J.L.C., M.J.H., S. D. Davis, S. D. Dell, T.W.F., S.D.S., K.N.O., M.R.,
C.E.M., and M.A.Z), by NIH-NHLBI grants 5R01HL071798 and 1R01HL117836
(M.R.K., L.E.O., and M.A.Z.), by NIH-NHGRI grant 1 U54HG006493 (M.J.B.,
DAN., and J.S.), and by NIH-R01 DK068306 (F.H.). K.N.O. is supported by
the Intramural Research Program of the NIH-NIAID. Resequencing was
provided through RS&G by NIH-NHLBI contract # HHSN268201100037C. The
work was supported by NIH-NCATS grants UL1TR000083 to University of
North Carolina, Chapel Hill, UL1TR000154 to University of Colorado CTSI,
Cystic Fibrosis Foundation grants CFF R026-CRO7 and R026-CR11, and
NIH-NIDDK grant P30-DK065988. The content is solely the responsibility
of the authors and does not necessarily represent the official view of
the NIH.
NR 51
TC 35
Z9 36
U1 1
U2 13
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 MAR 15
PY 2014
VL 189
IS 6
BP 707
EP 717
DI 10.1164/rccm.201311-20470C
PG 11
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA AD6OQ
UT WOS:000333381100015
PM 24568568
ER
PT J
AU Mahmood, SS
Levy, D
Vasan, RS
Wang, TJ
AF Mahmood, Syed S.
Levy, Daniel
Vasan, Ramachandran S.
Wang, Thomas J.
TI The Framingham Heart Study and the epidemiology of cardiovascular
disease: a historical perspective
SO LANCET
LA English
DT Review
ID ISOLATED SYSTOLIC HYPERTENSION; POPULATION-BASED COHORT;
ATRIAL-FIBRILLATION; RISK-FACTORS; FOLLOW-UP; MYOCARDIAL-INFARCTION;
DIABETES-MELLITUS; NATURAL-HISTORY; BLOOD PRESSURE; FAILURE
AB On Sept 29, 2013, the Framingham Heart Study will celebrate 65 years since the examination of the first volunteer in 1948. During this period, the study has provided substantial insight into the epidemiology and risk factors of cardiovascular disease. The origins of the study are closely linked to the cardiovascular health of President Franklin D Roosevelt and his premature death from hypertensive heart disease and stroke in 1945. In this Review we describe the events leading to the foundation of the Framingham Heart Study, and provide a brief historical overview of selected contributions from the study.
C1 [Mahmood, Syed S.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA.
[Levy, Daniel; Vasan, Ramachandran S.; Wang, Thomas J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Levy, Daniel] NHLBI, Populat Res Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA.
[Wang, Thomas J.] Vanderbilt Univ, Div Cardiovasc Med, Nashville, TN 37235 USA.
RP Wang, TJ (reprint author), Vanderbilt Univ Sch Med, Div Cardiovasc Med, Nashville, TN 37232 USA.
EM thomas.j.wang@vanderbilt.edu
OI Mahmood, Syed Saad/0000-0001-6938-1321; Ramachandran,
Vasan/0000-0001-7357-5970
FU NIH [N01-HC-25195]
FX We thank Paul Sorlie (National Heart, Lung, and Blood Institute,
Bethesda, MD, USA) for his assistance in granting access to the
Framingham Archives. We thank Gerald Oppenheimer (Department of
Sociomedical Sciences, Columbia University, New York, NY, USA) for
comments on the history of the Framingham Heart Study. This work was
supported by NIH contract N01-HC-25195.
NR 81
TC 79
Z9 86
U1 8
U2 36
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
EI 1474-547X
J9 LANCET
JI Lancet
PD MAR 15
PY 2014
VL 383
IS 9921
BP 999
EP 1008
DI 10.1016/S0140-6736(13)61752-3
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA AD8MR
UT WOS:000333520700030
PM 24084292
ER
PT J
AU Vogel, SS
van der Meer, BW
Blank, PS
AF Vogel, Steven S.
van der Meer, B. Wieb
Blank, Paul S.
TI Estimating the distance separating fluorescent protein FRET pairs
SO METHODS
LA English
DT Article
DE GFP; Kappa squared
ID ENERGY-TRANSFER; LIVING CELLS; MOLECULAR-SPECTROSCOPY; GREEN; DYNAMICS;
MATURATION; MICROSCOPY; ACCEPTORS; VENUS
AB Forster resonance energy transfer (FRET) describes a physical phenomenon widely applied in biomedical research to estimate separations between biological molecules. Routinely, genetic engineering is used to incorporate spectral variants of the green fluorescent protein (GFPs), into cellular expressed proteins. The transfer efficiency or rate of energy transfer between donor and acceptor FPs is then assayed. As appreciable FRET occurs only when donors and acceptors are in close proximity (1-10 nm), the presence of FRET may indicate that the engineered proteins associate as interacting species. For a homogeneous population of FRET pairs the separations between FRET donors and acceptors can be estimated from a measured FRET efficiency if it is assumed that donors and acceptors are randomly oriented and rotate extensively during their excited state (dynamic regime). Unlike typical organic fluorophores, the rotational correlation-times of FPs are typically much longer than their fluorescence lifetime; accordingly FPs are virtually static during their excited state. Thus, estimating separations between FP FRET pairs is problematic. To overcome this obstacle, we present here a simple method for estimating separations between FPs using the experimentally measured average FRET efficiency. This approach assumes that donor and acceptor fluorophores are randomly oriented, but do not rotate during their excited state (static regime). This approach utilizes a Monte-Carlo simulation generated look-up table that allows one to estimate the separation, normalized to the Forster distance, from the average FRET efficiency. Assuming a dynamic regime overestimates the separation significantly (by 10% near 0.5 and 30% near 0.75 efficiencies) compared to assuming a static regime, which is more appropriate for estimates of separations between FPs. (C) 2013 Published by Elsevier Inc.
C1 [Vogel, Steven S.] NIAAA, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA.
[van der Meer, B. Wieb] Western Kentucky Univ, Dept Phys & Astron, Bowling Green, KY 42101 USA.
[Blank, Paul S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD 20892 USA.
RP Vogel, SS (reprint author), NIAAA, Lab Mol Physiol, NIH, 5625 Fishers Lane,Room TS-06F MSC 9411, Bethesda, MD 20892 USA.
EM stevevog@mail.nih.gov
OI Vogel, Steven/0000-0002-3005-2667
FU intramural programs of the National Institutes of Health, National
Institute on Alcohol Abuse and Alcoholism; Eunice Kennedy Shriver
National Institute of Child Health and Human Development Bethesda, MD,
USA
FX This work was funded by intramural programs of the National Institutes
of Health, National Institute on Alcohol Abuse and Alcoholism, and the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development Bethesda, MD 20892, USA.
NR 34
TC 14
Z9 14
U1 3
U2 29
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1046-2023
EI 1095-9130
J9 METHODS
JI Methods
PD MAR 15
PY 2014
VL 66
IS 2
BP 131
EP 138
DI 10.1016/j.ymeth.2013.06.021
PG 8
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AE1ZM
UT WOS:000333773100003
PM 23811334
ER
PT J
AU Gahl, RF
Tekle, E
Tjandra, N
AF Gahl, Robert F.
Tekle, Ephrem
Tjandra, Nico
TI Single color FRET based measurements of conformational changes of
proteins resulting from translocation inside cells
SO METHODS
LA English
DT Article
DE FRET; Live-cell imaging; Microinjection; Translocation; Apoptosis;
Conformational changes
ID APOPTOSIS; BAX; MITOCHONDRIA; CYTOSOL
AB Translocation of proteins to different parts of the cell is necessary for many cellular mechanisms as a means for regulation and a variety of other functions. Identifying how these proteins undergo conformational changes or interact with various partners during these events is critical to understanding how these mechanisms are executed. A protocol is presented that identifies conformational changes in a protein that occur during translocation while overcoming challenges in extracting distance information in very different environments of a living cell. Only two samples are required to be prepared and are observed with one optical setup. Live-cell FRET imaging has been applied to identify conformational changes between two native cysteines in Bax, a member of the Bcl-2 family of proteins that regulates apoptosis. Bax exists in the cytosol and translocates to the mitochondria outer membrane upon apoptosis induction. The distance, r, between the two native cysteines in the cytosolic structure of Bax necessitates the use of a FRET donor accepter pair with R-0 similar to r as the most sensitive probe for identifying structural changes at these positions. Alexa Fluor 546 and Dabcyl, a dark acceptor, were used as FRET pairs resulting in single color intensity variations of Alexa-546 as a measure of FRET efficiency. An internal reference, conjugated to Bax, was employed to normalize changes in fluorescence intensity of Alexa Fluor 546 due to inherent inhomogeneities in the living cell. This correction allowed the true FRET effects to be measured with increased precision during translocation. Normalization of intensities to the internal reference identified a FRET efficiency of 0.45 +/- 0.14 in the cytosol and 0.11 +/- 0.20 in the mitochondria. The procedure for the conjugation of the internal reference and FRET probes as well as the data analysis is presented. Published by Elsevier Inc.
C1 [Gahl, Robert F.; Tjandra, Nico] NHLBI, Lab Mol Biophys, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA.
[Tekle, Ephrem] NHLBI, Biochem Lab, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA.
RP Tjandra, N (reprint author), NHLBI, Lab Mol Biophys, Biochem & Biophys Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM tjandran@nhlbi.nih.gov
FU Intramural Research Programs of National Heart, Lung, and Blood
Institute of the NIH
FX This work was supported by the Intramural Research Programs of National
Heart, Lung, and Blood Institute of the NIH.
NR 18
TC 4
Z9 4
U1 1
U2 16
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1046-2023
EI 1095-9130
J9 METHODS
JI Methods
PD MAR 15
PY 2014
VL 66
IS 2
BP 180
EP 187
DI 10.1016/j.ymeth.2013.07.011
PG 8
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AE1ZM
UT WOS:000333773100008
PM 23872323
ER
PT J
AU Rahim, NAA
Pelet, S
Mofrad, MRK
So, PTC
Kamm, RD
AF Rahim, Nur Aida Abdul
Pelet, Serge
Mofrad, Mohammad R. K.
So, Peter T. C.
Kamm, Roger D.
TI Quantifying intracellular protein binding thermodynamics during
mechanotransduction based on FRET spectroscopy
SO METHODS
LA English
DT Article
DE FRET; FLIM; FCS; Mechanotransduction; Paxillin; Focal adhesion kinase
ID CROSS-CORRELATION SPECTROSCOPY; FOCAL ADHESION KINASE; FLUORESCENCE
CORRELATION SPECTROSCOPY; ISOTHERMAL TITRATION CALORIMETRY; LIVING
CELLS; IMAGING MICROSCOPY; IN-VIVO; TYROSINE PHOSPHORYLATION; 2-PHOTON
EXCITATION; ENDOTHELIAL-CELLS
AB Mechanical force modulates myriad cellular functions including migration, alignment, proliferation, and gene transcription. Mechanotransduction, the transmission of mechanical forces and its translation into biochemical signals, may be mediated by force induced protein conformation changes, subsequently modulating protein signaling. For the paxillin and focal adhesion kinase interaction, we demonstrate that force-induced changes in protein complex conformation, dissociation constant, and binding Gibbs free energy can be quantified by lifetime-resolved fluorescence energy transfer microscopy combined with intensity imaging calibrated by fluorescence correlation spectroscopy. Comparison with in vitro data shows that this interaction is allosteric in vivo. Further, spatially resolved imaging and inhibitor assays show that this protein interaction and its mechano-sensitivity are equal in the cytosol and in the focal adhesions complexes indicating that the mechano-sensitivity of this interaction must be mediated by soluble factors but not based on protein tyrosine phosphorylation. (C) 2013 Published by Elsevier Inc.
C1 [Rahim, Nur Aida Abdul; So, Peter T. C.; Kamm, Roger D.] MIT, Dept Mech Engn, Cambridge, MA 02139 USA.
[Pelet, Serge; So, Peter T. C.; Kamm, Roger D.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA.
[Pelet, Serge] Univ Lausanne, Dept Fundamental Microbiol, CH-1015 Lausanne, Switzerland.
[Mofrad, Mohammad R. K.] Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA.
[So, Peter T. C.] MIT, Laser Biomed Res Ctr, A NIH NIBIB Res Resource, Cambridge, MA 02139 USA.
RP So, PTC (reprint author), MIT, Dept Mech & Biol Engn, NE47-279,77 Mass Ave, Cambridge, MA 02139 USA.
EM ptso@mit.edu
OI Pelet, Serge/0000-0002-0245-049X; /0000-0002-7232-304X
FU NIH [9P41EB015871-26A1, R01-EX017656, 5 R01 NS051320, 4R44EB012415-02];
NSF [CBET-0939511]; National Research Foundation Singapore through the
Singapore MIT Alliance for Research and Technology's BioSym research
programme; Singapore-MIT Alliance 2; MIT SkolTech initiative; MIT-Dana
Fabre Cancer Center Bridge Funding; McGovern Institute Neurotechnology
(MINT) program; Hamamatsu Corporation
FX PTCSO acknowledges supports from: NIH 9P41EB015871-26A1, R01-EX017656, 5
R01 NS051320, 4R44EB012415-02, NSF CBET-0939511, the National Research
Foundation Singapore through the Singapore MIT Alliance for Research and
Technology's BioSym research programme, the Singapore-MIT Alliance 2,
the MIT SkolTech initiative, the MIT-Dana Fabre Cancer Center Bridge
Funding, The McGovern Institute Neurotechnology (MINT) program, and the
Hamamatsu Corporation. The authors would also like to thank Prof. Keith
Berland of Emory University for his invaluable suggestion in combining
intensity imaging with FCS calibration to quantify the concentration of
green and red diffusing species in the cells.
NR 71
TC 3
Z9 3
U1 0
U2 9
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1046-2023
EI 1095-9130
J9 METHODS
JI Methods
PD MAR 15
PY 2014
VL 66
IS 2
BP 208
EP 221
DI 10.1016/j.ymeth.2013.10.007
PG 14
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AE1ZM
UT WOS:000333773100011
ER
PT J
AU Vidarsdottir, H
Fang, F
Chang, M
Aspelund, T
Fall, K
Jonsdottir, MK
Jonsson, PV
Cotch, MF
Harris, TB
Launer, LJ
Gudnason, V
Valdimarsdottir, U
AF Vidarsdottir, Halldora
Fang, Fang
Chang, Milan
Aspelund, Thor
Fall, Katja
Jonsdottir, Maria K.
Jonsson, Palmi V.
Cotch, Mary Frances
Harris, Tamara B.
Launer, Lenore J.
Gudnason, Vilmundur
Valdimarsdottir, Unnur
TI Spousal Loss and Cognitive Function in Later Life: A 25-year Follow-up
in the AGES-Reykjavik Study
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE dementia; executive function; marital status; memory; psychological
stress
ID WHITE-MATTER LESIONS; ALZHEIMERS-DISEASE; MARITAL-STATUS; OLDER-ADULTS;
MYOCARDIAL-INFARCTION; MEMORY PERFORMANCE; SOCIAL NETWORK; STRESS;
DEMENTIA; RISK
AB The aim of this study was to investigate the associations between loss of a life partner and the development of dementia and decline in cognitive function in later life. We used an Icelandic cohort of 4,370 participants in the Age, Gene/Environment Susceptibility-Reykjavik Study who were living as married in 1978 (born in 1907-1935) and were either still married (unexposed cohort) or widowed (exposed cohort) at follow-up (in 2002-2006). We ascertained history of marital status and spouse's death by record linkage to the Registry of the Total Population, Statistics Iceland. The outcome measures were as follows: 1) dementia and mild cognitive impairment; and 2) memory, speed of processing, and executive function. During the observation period, 3,007 individuals remained married and 1,363 lost a spouse through death. We did not find any significant associations between loss of a spouse and our outcome variables, except that widowed women had poorer executive function (mean = -0.08) during the first 2 years after their husbands' deaths compared with still-married women (mean = 0.09). Our findings do not support the notion that the risk of dementia is increased following the loss of a spouse, yet women demonstrate a seemingly temporary decline in executive function following the death of a partner.
C1 [Vidarsdottir, Halldora; Aspelund, Thor; Valdimarsdottir, Unnur] Univ Iceland, Ctr Publ Hlth Sci, IS-101 Reykjavik, Iceland.
[Fang, Fang] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Chang, Milan; Jonsdottir, Maria K.; Jonsson, Palmi V.] Natl Univ Hosp Reykjavik, Geriatr Res Ctr, Reykjavik, Iceland.
[Chang, Milan] Reykjavik Univ, Sch Sci & Engn, Dept Sports Sci, Reykjavik, Iceland.
[Aspelund, Thor; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Fall, Katja] Orebro Univ Hosp, Dept Clin Epidemiol & Biostat, Orebro, Sweden.
[Jonsdottir, Maria K.] Univ Iceland, Fac Psychol, IS-101 Reykjavik, Iceland.
[Jonsson, Palmi V.; Gudnason, Vilmundur] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.
[Jonsson, Palmi V.] Natl Univ Hosp Reykjavik, Dept Geriatr, Reykjavik, Iceland.
[Cotch, Mary Frances] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
[Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA.
[Valdimarsdottir, Unnur] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
RP Vidarsdottir, H (reprint author), Univ Iceland, Ctr Publ Hlth Sci, Stapi v-Hringbraut, IS-101 Reykjavik, Iceland.
EM halldvi@hi.is
RI Aspelund, Thor/C-5983-2008; Gudnason, Vilmundur/K-6885-2015;
OI Aspelund, Thor/0000-0002-7998-5433; Gudnason,
Vilmundur/0000-0001-5696-0084; Cotch, Mary Frances/0000-0002-2046-4350;
Fang, Fang/0000-0002-3310-6456; Fall, Katja/0000-0002-3649-2639
FU University of Iceland Research Fund for Graduate Students; Icelandic
Research Fund for Graduate Students (Rannis); Memorial Fund of Helga
Jonsdottir and Sigurlidi Kristjansson; Research Fund of Oldrunarrad
Islands; Icelandic Gerontological Society Research Fund; Fund of
Gudmundur Andresson; Swedish Society for Medical Research; National
Institute on Aging [N01-AG-1-2100]; National Institute on Aging;
Icelandic Parliament; Icelandic Heart Association
FX H.V. was supported by the University of Iceland Research Fund for
Graduate Students, the Icelandic Research Fund for Graduate Students
(Rannis), the Memorial Fund of Helga Jonsdottir and Sigurlidi
Kristjansson, the Research Fund of Oldrunarrad Islands, the Icelandic
Gerontological Society Research Fund, and the Fund of Gudmundur
Andresson. F. F. was supported by a postdoctoral fellowship from the
Swedish Society for Medical Research. This study was also funded in part
by the National Institute on Aging (contract N01-AG-1-2100), the
intramural research program of the National Institute on Aging, the
Icelandic Heart Association, and the Icelandic Parliament.
NR 47
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U1 1
U2 13
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
EI 1476-6256
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD MAR 15
PY 2014
VL 179
IS 6
BP 674
EP 683
DI 10.1093/aje/kwt321
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AD4UP
UT WOS:000333246800004
PM 24444551
ER
PT J
AU Nogueira, L
Freedman, ND
Engels, EA
Warren, JL
Castro, F
Koshiol, J
AF Nogueira, Leticia
Freedman, Neal D.
Engels, Eric A.
Warren, Joan L.
Castro, Felipe
Koshiol, Jill
TI Gallstones, Cholecystectomy, and Risk of Digestive System Cancers
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE cancer; cholecystectomy; digestive system; gallstones; gastric cancer;
liver; pancreas
ID POPULATION-BASED COHORT; LARGE-BOWEL-CANCER; COLORECTAL-CANCER;
PANCREATIC-CANCER; BILE-ACIDS; COLON-CANCER; DIABETES-MELLITUS;
EXTRAHEPATIC CHOLANGIOCARCINOMA; UNITED-STATES; BILIARY-TRACT
AB Gallstones and cholecystectomy may be related to digestive system cancer through inflammation, altered bile flux, and changes in metabolic hormone levels. Although gallstones are recognized causes of gallbladder cancer, associations with other cancers of the digestive system are poorly established. We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database (1992-2005), which includes 17 cancer registries that cover approximately 26% of the US population, to identify first primary cancers (n = 236,850) occurring in persons aged = 66 years and 100,000 cancer-free population-based controls frequency-matched by calendar year, age, and gender. Odds ratios and 95% confidence intervals were calculated using logistic regression analysis, adjusting for the matching factors. Gallstones and cholecystectomy were associated with increased risk of noncardia gastric cancer (odds ratio (OR) = 1.21 (95% confidence interval (CI): 1.11, 1.32) and OR = 1.26 (95% CI: 1.13, 1.40), respectively), small-intestine carcinoid (OR = 1.27 (95% CI: 1.01, 1.60) and OR = 1.78 (95% CI: 1.41, 2.25)), liver cancer (OR = 2.35 (95% CI: 2.18, 2.54) and OR = 1.26 (95% CI: 1.12, 1.41)), and pancreatic cancer (OR = 1.24 (95% CI: 1.16, 1.31) and OR = 1.23 (95% CI: 1.15, 1.33)). Colorectal cancer risk associated with gallstones and cholecystectomy decreased with increasing distance from the common bile duct (P-trend < 0.001). Hence, gallstones and cholecystectomy are associated with the risk of cancers occurring throughout the digestive tract.
C1 [Nogueira, Leticia; Engels, Eric A.; Castro, Felipe; Koshiol, Jill] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol, Bethesda, MD 20892 USA.
[Freedman, Neal D.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Warren, Joan L.] NCI, Hlth Serv & Econ Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Nogueira, L (reprint author), NCI, 9609 Med Ctr Dr,MSC 7248, Bethesda, MD 20892 USA.
EM leticia.nogueira@nih.gov
RI Freedman, Neal/B-9741-2015
OI Freedman, Neal/0000-0003-0074-1098
NR 92
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Z9 16
U1 2
U2 11
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
EI 1476-6256
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD MAR 15
PY 2014
VL 179
IS 6
BP 731
EP 739
DI 10.1093/aje/kwt322
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AD4UP
UT WOS:000333246800010
PM 24470530
ER
PT J
AU Yang, PY
Patrick, E
Tan, SX
Fazakerley, DJ
Burchfield, J
Gribben, C
Prior, MJ
James, DE
Yang, YH
AF Yang, Pengyi
Patrick, Ellis
Tan, Shi-Xiong
Fazakerley, Daniel J.
Burchfield, James
Gribben, Christopher
Prior, Matthew J.
James, David E.
Yang, Yee Hwa
TI Direction pathway analysis of large-scale proteomics data reveals novel
features of the insulin action pathway
SO BIOINFORMATICS
LA English
DT Article
ID SET ENRICHMENT ANALYSIS; GENE-EXPRESSION DATA; GOODNESS-OF-FIT; GLUT4
TRAFFICKING; 3T3-L1 ADIPOCYTES; PLASMA-MEMBRANE; METAANALYSIS;
PLATFORMS; KNOWLEDGE; TOOLS
AB Motivation: With the advancement of high-throughput techniques, large-scale profiling of biological systems with multiple experimental perturbations is becoming more prevalent. Pathway analysis incorporates prior biological knowledge to analyze genes/proteins in groups in a biological context. However, the hypotheses under investigation are often confined to a 1D space (i.e. up, down, either or mixed regulation). Here, we develop direction pathway analysis (DPA), which can be applied to test hypothesis in a high-dimensional space for identifying pathways that display distinct responses acrossmultiple perturbations.
Results: Our DPA approach allows for the identification of pathways that display distinct responses across multiple perturbations. To demonstrate the utility and effectiveness, we evaluated DPA under various simulated scenarios and applied it to study insulin action in adipocytes. A major action of insulin in adipocytes is to regulate the movement of proteins from the interior to the cell surface membrane. Quantitative mass spectrometry-based proteomics was used to study this process on a large-scale. The combined dataset comprises four separate treatments. By applying DPA, we identified that several insulin responsive pathways in the plasma membrane trafficking are only partially dependent on the insulin-regulated kinase Akt. We subsequently validated our findings through targeted analysis of key proteins from these pathways using immunoblotting and live cell microscopy. Our results demonstrate that DPA can be applied to dissect pathway networks testing diverse hypotheses and integrating multiple experimental perturbations.
C1 [Yang, Pengyi] NIEHS, Syst Biol Grp, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Yang, Pengyi; Patrick, Ellis; Yang, Yee Hwa] Univ Sydney, Sch Math & Stat, Sydney, NSW 2006, Australia.
[Yang, Pengyi; Tan, Shi-Xiong; Fazakerley, Daniel J.; Burchfield, James; Gribben, Christopher; Prior, Matthew J.; James, David E.] Garvan Inst Med Res, Diabet & Obes Program, Sydney, NSW 2006, Australia.
[Tan, Shi-Xiong] ASTAR, Inst Mol & Cellular Biol, Metab Human Dis Unit, Proteos 138673, Singapore.
RP Yang, YH (reprint author), Univ Sydney, Sch Math & Stat, Sydney, NSW 2006, Australia.
EM jean.yang@sydney.edu.au
RI Yang, Pengyi/B-1002-2010; Yang, Jean /D-2920-2015;
OI Yang, Pengyi/0000-0003-1098-3138; Yang, Jean /0000-0002-5271-2603;
Patrick, Ellis/0000-0002-5253-4747
FU Australian Research Council (ARC) [FT0991918, DP0984267]; National
Health and Medical Research Council (NHMRC); NHMRC Senior Principal
Research
FX Australian Research Council (ARC) grants (FT0991918 and DP0984267 to
Y.Y.) and by an National Health and Medical Research Council (NHMRC)
program grant (to D.E.J.). D.E.J. is also recipient of an NHMRC Senior
Principal Research. D.F. is a Sir Henry Wellcome Post-Doctoral Fellow of
the Wellcome Trust.
NR 34
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U1 0
U2 12
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
EI 1460-2059
J9 BIOINFORMATICS
JI Bioinformatics
PD MAR 15
PY 2014
VL 30
IS 6
BP 808
EP 814
DI 10.1093/bioinformatics/btt616
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 AD4VR
UT WOS:000333249900010
PM 24167158
ER
PT J
AU Xu, SW
Liu, ZP
Liu, PQ
AF Xu, Suowen
Liu, Zhiping
Liu, Peiqing
TI Targeting hydrogen sulfide as a promising therapeutic strategy for
atherosclerosis
SO INTERNATIONAL JOURNAL OF CARDIOLOGY
LA English
DT Review
DE Atherosclerosis; Cystathionine gamma-lyase; Gasotransmitter; Hydrogen
sulfide
ID CYSTATHIONINE GAMMA-LYASE; E KNOCKOUT MICE; LOW-DENSITY-LIPOPROTEIN;
SMOOTH-MUSCLE-CELLS; ACCELERATES ATHEROSCLEROSIS; SIGNALING PATHWAYS;
DIALLYL DISULFIDE; DEFICIENT MICE; NITRIC-OXIDE; OXIDIZED LDL
AB Physiological concentrations of nitric oxide (NO) and carbon monoxide (CO) have multiple protective effects in the cardiovascular system. Recent studies have implicated hydrogen sulfide (H2S) as a new member of vasculoprotective gasotransmitter family, behaving similarly to NO and CO. H2S has been demonstrated to inhibit multiple key aspects of atherosclerosis, including atherogenic modification of LDL, monocytes adhesion to the endothelial cells, macrophage-derived foam cell formation and inflammation, smooth muscle cell proliferation, neointimal hyperplasia, vascular calcification, and thrombogenesis. H2S also decreases plasma homocysteine levels in experimental animal models. In the human body, H2S production is predominantly catalyzed by cystathionine-beta-synthase (CBS) and cystathionine.-lyase (CSE). CSE is the primary H2S-producing enzyme in the vasculature. Growing evidence suggests that atherosclerosis is associated with vascular CSE/H2S deficiency and that H2S supplementation by exogenous H2S donors (such as NaHS and GYY4137) attenuates, and H2S synthesis suppression by inhibitors (such as D, L-propargylglycine) aggravates the development of atherosclerotic plaques. However, it remains elusive whether CSE deficiency plays a causative role in atherosclerosis. A recent study (Circulation. 2013; 127: 2523-2534) demonstrates that decreased endogenous H2S production by CSE genetic deletion accelerates atherosclerosis in athero-prone ApoE(-/-) mice, pinpointing that endogenously produced H2S by CSE activation may be of benefit in the prevention and treatment of atherosclerosis. This study will facilitate the development of H2S-based pharmaceuticals with therapeutic applications in atherosclerosis-related cardiovascular diseases. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
C1 [Xu, Suowen; Liu, Zhiping; Liu, Peiqing] Sun Yat Sen Univ, Sch Pharmaceut Sci, Dept Pharmacol & Toxicol, Guangzhou 510006, Guangdong, Peoples R China.
[Xu, Suowen] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA.
RP Xu, SW (reprint author), NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM suowen.xu@gmail.com; liupq@mail.sysu.edu.cn
FU National Natural Science Foundation of China [81072641, 81273499];
National Science and Technology Major Project of China "Key New Drug
Creation and Manufacturing Program" [2011ZX09401-307]; Team Item of the
Natural Science Foundation of Guangdong Province [S2011030003190]; Major
Project of Guangdong Province [2008A030201013, 2012A080201007]; Major
Project of Department of Education of Guangdong Province [CXZD1006];
Ministry of Education of China
FX The authors gratefully acknowledge the financial support from the
National Natural Science Foundation of China (No. 81072641 and No.
81273499), the National Science and Technology Major Project of China
"Key New Drug Creation and Manufacturing Program" (No. 2011ZX09401-307),
Team Item of the Natural Science Foundation of Guangdong Province (No.
S2011030003190), Major Project of Guangdong Province (No. 2008A030201013
and No. 2012A080201007), and Major Project of Department of Education of
Guangdong Province (No. CXZD1006). S.X. is a recipient of "New
Investigator Award" from the Ministry of Education of China. The authors
of this manuscript have certified that they comply with the Principles
of Ethical Publishing in the International Journal of Cardiology.
NR 50
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U1 1
U2 27
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0167-5273
EI 1874-1754
J9 INT J CARDIOL
JI Int. J. Cardiol.
PD MAR 15
PY 2014
VL 172
IS 2
BP 313
EP 317
PG 5
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AC5AC
UT WOS:000332531800055
PM 24491853
ER
PT J
AU Liu, CY
Bluemke, DA
Gerstenblith, G
Zimmerman, SL
Li, J
Zhu, H
Lai, SH
Lai, H
AF Liu, Chia-Ying
Bluemke, David A.
Gerstenblith, Gary
Zimmerman, Stefan L.
Li, Ji
Zhu, Hong
Lai, Shenghan
Lai, Hong
TI Myocardial steatosis and its association with obesity and regional
ventricular dysfunction: Evaluated by magnetic resonance tagging and H-1
spectroscopy in healthy African Americans
SO INTERNATIONAL JOURNAL OF CARDIOLOGY
LA English
DT Article
DE Cardiac steatosis; African Americans; MR tagging; MR spectroscopy; LV
regional function
ID HEART-DISEASE; DIABETES-MELLITUS; HARP MRI; HUMANS; LEPTIN;
REPRODUCIBILITY; TRIGLYCERIDE; MECHANISMS
AB Background: Cardiac steatosis is common in patients with diabetes or obesity, and cardiac steatosis may result in cardiomyopathy. However, factors associated with cardiac steatosis have not been reported in healthy individuals without diabetes and hypertension. The objectives of this study were to explore factors associated with myocardial triglyceride levels, and to examine the association between myocardial triglyceride and regional left ventricular (LV) function in healthy African Americans (AAs).
Methods: Between November 2010 and June 2012, 92 healthy AAs aged 21 years or older, without clinical evidence of cardiac dysfunction, coronary artery disease, diabetes, or hypertension from Baltimore, Maryland, were enrolled in an observational proton magnetic resonance spectroscopy and imaging study investigating factors associated with cardiac steatosis, and the relationships between cardiac steatosis and LV volumes and LV function.
Results: Among the participants, all had a low Framingham risk; 31 had a normal BMI, 23 were overweight and 38 were obese. The median myocardial triglyceride content was 0.5% (IQR: 0.3-1.0%). Among the factors investigated, BMI (R-2= 0.43, p= < 0.0001) was independently associated with myocardial triglyceride. Overall, myocardial triglyceride was not associated with LV EF/structure, but may be associated with regional LV function.
Conclusions: In healthy AA adults, obesity is associated with cardiac steatosis. In contrast to studies in patients with diabetes suggesting a link between cardiac steatosis and LV dysfunction, this study found no relationship between cardiac steatosis and left ventricular volumes or EF, though there is some evidence suggesting that cardiac steatosis may be associated with LV regional function in healthy AA women. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
C1 [Liu, Chia-Ying; Bluemke, David A.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Gerstenblith, Gary; Lai, Shenghan] Johns Hopkins Sch Med, Dept Med, Baltimore, MD 21287 USA.
[Zimmerman, Stefan L.; Lai, Shenghan; Lai, Hong] Johns Hopkins Sch Med, Dept Radiol, Baltimore, MD 21287 USA.
[Li, Ji; Zhu, Hong; Lai, Shenghan] Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD 21287 USA.
[Zhu, Hong] Tianjin Med Univ, Dept Epidemiol & Biostat, Tianjin, Peoples R China.
RP Lai, SH (reprint author), Johns Hopkins Sch Med, 600 N Wolfe St, Baltimore, MD 21287 USA.
EM slai@jhmi.edu
OI Bluemke, David/0000-0002-8323-8086
FU National Institute on Drug Abuse; National Institutes of Health (NIH)
[R01-DA 12777, DA25524, DA15020]
FX We thank the study participants for their contributions. The study was
supported by grants from the National Institute on Drug Abuse, National
Institutes of Health (NIH R01-DA 12777, DA25524 and DA15020).
NR 23
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U1 1
U2 5
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0167-5273
EI 1874-1754
J9 INT J CARDIOL
JI Int. J. Cardiol.
PD MAR 15
PY 2014
VL 172
IS 2
BP 381
EP 387
DI 10.1016/j.ijcard.2014.01.074
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AC5AC
UT WOS:000332531800065
PM 24507737
ER
PT J
AU Olivieri, L
Krieger, A
Chen, MY
Kim, P
Kanter, JP
AF Olivieri, Laura
Krieger, Axel
Chen, Marcus Y.
Kim, Peter
Kanter, Joshua P.
TI 3D heart model guides complex stent angioplasty of pulmonary venous
baffle obstruction in a Mustard repair of D-TGA
SO INTERNATIONAL JOURNAL OF CARDIOLOGY
LA English
DT Letter
DE Congenital heart disease; Cardiac interventions; Transposition of the
great arteries; Computed tomography; 3D printing
C1 [Olivieri, Laura; Kanter, Joshua P.] Childrens Natl Med Ctr, Div Cardiol, Washington, DC 20010 USA.
[Olivieri, Laura; Krieger, Axel; Kim, Peter; Kanter, Joshua P.] Childrens Natl Med Ctr, Sheik Zayed Inst Pediat Surg Innovat, Washington, DC 20010 USA.
[Chen, Marcus Y.] NHLBI, NIH, Adv Cardiovasc Imaging Lab, Bethesda, MD 20892 USA.
RP Olivieri, L (reprint author), Childrens Natl Med Ctr, Div Cardiol, 111 Michigan Ave NW Suite W3-200, Washington, DC 20010 USA.
EM lolivier@childrensnational.org
NR 6
TC 22
Z9 28
U1 0
U2 16
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0167-5273
EI 1874-1754
J9 INT J CARDIOL
JI Int. J. Cardiol.
PD MAR 15
PY 2014
VL 172
IS 2
BP E297
EP E298
DI 10.1016/j.ijcard.2013.12.192
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AC5AC
UT WOS:000332531800015
PM 24447757
ER
PT J
AU Han, S
Lin, YC
Wu, TX
Salgado, AD
Mexhitaj, I
Wuest, SC
Romm, E
Ohayon, J
Goldbach-Mansky, R
Vanderver, A
Marques, A
Toro, C
Williamson, P
Cortese, I
Bielekova, B
AF Han, Sungpil
Lin, Yen Chih
Wu, Tianxia
Salgado, Alan D.
Mexhitaj, Ina
Wuest, Simone C.
Romm, Elena
Ohayon, Joan
Goldbach-Mansky, Raphaela
Vanderver, Adeline
Marques, Adriana
Toro, Camilo
Williamson, Peter
Cortese, Irene
Bielekova, Bibiana
TI Comprehensive Immunophenotyping of Cerebrospinal Fluid Cells in Patients
with Neuroimmunological Diseases
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID PROGRESSIVE MULTIPLE-SCLEROSIS; CENTRAL-NERVOUS-SYSTEM; PLASMACYTOID
DENDRITIC CELLS; AICARDI-GOUTIERES SYNDROME; HERPES-SIMPLEX-VIRUS;
T-CELLS; B-CELLS; MENINGEAL INFLAMMATION; CNS REMYELINATION;
IMMUNE-RESPONSES
AB We performed unbiased, comprehensive immunophenotyping of cerebrospinal fluid (CSF) and blood leukocytes in 221 subjects referred for the diagnostic work-up of neuroimmunological disorders to obtain insight about disease-specific phenotypes of intrathecal immune responses. Quantification of 14 different immune cell subsets, coupled with the assessment of their activation status, revealed physiological differences between intrathecal and systemic immunity, irrespective of final diagnosis. Our data are consistent with a model where the CNS shapes intrathecal immune responses to provide effective protection against persistent viral infections, especially by memory T cells, plasmacytoid dendritic cells, and CD56(bright) NK cells. Our data also argue that CSF immune cells do not simply reflect cells recruited from the periphery. Instead, they represent a mixture of cells that are recruited from the blood, have been activated intrathecally and leave the CNS after performing effector functions. Diagnosis-specific differences provide mechanistic insight into the disease process in the defined subtypes of multiple sclerosis (MS), neonatal onset multisystem inflammatory disease, and Aicardi-Goutieres syndrome. This analysis also determined that secondary-progressive MS patients are immunologically closer to relapsing-remitting patients as compared with patients with primary-progressive MS. Because CSF immunophenotyping captures the biology of the intrathecal inflammatory processes, it has the potential to guide optimal selection of immunomodulatory therapies in individual patients and monitor their efficacy. Our study adds to the increasing number of publications that demonstrate poor correlation between systemic and intrathecal inflammatory biomarkers in patients with neuroimmunological diseases and stresses the importance of studying immune responses directly in the intrathecal compartment.
C1 [Han, Sungpil; Lin, Yen Chih; Salgado, Alan D.; Mexhitaj, Ina; Wuest, Simone C.; Romm, Elena; Ohayon, Joan; Cortese, Irene; Bielekova, Bibiana] NINDS, Neuroimmunol Dis Unit, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA.
[Han, Sungpil] Pusan Natl Univ, Sch Med, Yangsan 626870, South Korea.
[Wu, Tianxia] NINDS, Clin Neurosci Program, NIH, Bethesda, MD 20892 USA.
[Goldbach-Mansky, Raphaela] NIAMSD, Translat Autoinflammatory Dis Sect, NIH, Bethesda, MD 20892 USA.
[Vanderver, Adeline] George Washington Univ, Childrens Natl Med Ctr, Dept Integrat Syst Biol, Washington, DC 20010 USA.
[Marques, Adriana] NIAID, Lab Clin Infect Dis, Clin Studies Unit, NIH, Bethesda, MD 20892 USA.
[Toro, Camilo] NHGRI, NIH, Undiagnosed Dis Program, Bethesda, MD 20892 USA.
[Williamson, Peter] NINDS, Translat Mycol Unit, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Bielekova, Bibiana] NIH, Ctr Human Immunol, Bethesda, MD 20892 USA.
RP Bielekova, B (reprint author), NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA.
EM Bibi.Bielekova@nih.gov
OI Han, Sungpil/0000-0002-4674-7682
FU National Institute of Neurological Disorders and Stroke/National
Institutes of Health
FX This work was supported by the intramural research program of the
National Institute of Neurological Disorders and Stroke/National
Institutes of Health.
NR 57
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U1 1
U2 8
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD MAR 15
PY 2014
VL 192
IS 6
BP 2551
EP 2563
DI 10.4049/jimmunol.1302884
PG 13
WC Immunology
SC Immunology
GA AC7IX
UT WOS:000332702700004
PM 24510966
ER
PT J
AU Kim, PS
Jochems, C
Grenga, I
Donahue, RN
Tsang, KY
Gulley, JL
Schlom, J
Farsaci, B
AF Kim, Peter S.
Jochems, Caroline
Grenga, Italia
Donahue, Renee N.
Tsang, Kwong Y.
Gulley, James L.
Schlom, Jeffrey
Farsaci, Benedetto
TI Pan-Bcl-2 Inhibitor, GX15-070 (Obatoclax), Decreases Human T Regulatory
Lymphocytes while Preserving Effector T Lymphocytes: A Rationale for Its
Use in Combination Immunotherapy
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID HISTONE DEACETYLASE INHIBITOR; CELL LUNG-CANCER; SYNERGISTIC
ANTILEUKEMIA ACTIVITY; DOMAIN-3 MIMETIC GX15-070; MCL-1 DOWN-REGULATION;
PHASE-I; FAMILY ANTAGONIST; BH3-MIMETIC GX15-070; ABT-737 RESISTANCE;
MESYLATE GX15-070
AB Bcl-2 inhibitors are currently being evaluated in clinical studies for treatment of patients with solid tumors and hematopoietic malignancies. In this study we explored the potential for combining the pan-Bcl-2 inhibitor GX15-070 (GX15; obatoclax) with immunotherapeutic modalities. We evaluated the in vitro effects of GX15 on human T cell subsets obtained from PBMCs in terms of activation, memory, and suppressive function. Our results indicated that in healthy-donor PBMCs, mature-activated T cells were more resistant to GX15 than early-activated T cells, and that GX15 preserved memory but not non-memory T cell populations. Furthermore, GX15 increased the apoptosis of regulatory T cells (Tregs), profoundly downregulated FOXP3 and CTLA-4 in a dose-dependent manner, and decreased their suppressive function. Treating PBMCs obtained from ovarian cancer patients with GX15 also resulted in increased CD8(+):Treg and CD4(+):Treg ratios. These results support preclinical studies in which mice vaccinated before treatment with GX15 showed the greatest reduction in metastatic lung tumors as a result of increased apoptotic resistance of mature CD8(+) T cells and decreased Treg function brought about by GX15. Taken together, these findings suggest that when a Bcl-2 inhibitor is combined with active immunotherapy in humans, such as the use of a vaccine or immune checkpoint inhibitor, immunotherapy should precede administration of the Bcl-2 inhibitor to allow T cells to become mature, and thus resistant to the cytotoxic effects of the Bcl-2 inhibitor.
C1 [Kim, Peter S.; Jochems, Caroline; Grenga, Italia; Donahue, Renee N.; Tsang, Kwong Y.; Gulley, James L.; Schlom, Jeffrey; Farsaci, Benedetto] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Schlom, J (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, 10 Ctr Dr,Room 8B09, Bethesda, MD 20892 USA.
EM js141c@nih.gov
RI Farsaci, Benedetto/L-9837-2014;
OI Farsaci, Benedetto/0000-0001-8275-2561; Kim, Peter/0000-0003-4108-299X
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health
FX This work was supported by the Intramural Research Program of the Center
for Cancer Research, National Cancer Institute, National Institutes of
Health.
NR 39
TC 11
Z9 11
U1 0
U2 2
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD MAR 15
PY 2014
VL 192
IS 6
BP 2622
EP 2633
DI 10.4049/jimmunol.1301369
PG 12
WC Immunology
SC Immunology
GA AC7IX
UT WOS:000332702700011
PM 24516200
ER
PT J
AU Robertson, SJ
Lubick, KJ
Freedman, BA
Carmody, AB
Best, SM
AF Robertson, Shelly J.
Lubick, Kirk J.
Freedman, Brett A.
Carmody, Aaron B.
Best, Sonja M.
TI Tick-Borne Flaviviruses Antagonize Both IRF-1 and Type I IFN Signaling
To Inhibit Dendritic Cell Function
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID WEST-NILE-VIRUS; JAPANESE ENCEPHALITIS-VIRUS; NF-KAPPA-B; INTERFERON
REGULATORY FACTOR-1; MOUSE EMBRYO FIBROBLASTS; IL-12 PRODUCTION;
GENE-EXPRESSION; DENGUE VIRUS; TRANSCRIPTION FACTORS; ADAPTIVE IMMUNITY
AB Tick-borne encephalitis virus (TBEV), a member of the Flaviviridae family, is a leading cause of viral encephalitis in Europe and Asia. Dendritic cells (DCs), as early cellular targets of infection, provide an opportunity for flaviviruses to inhibit innate and adaptive immune responses. Flaviviruses modulate DC function, but the mechanisms underpinning this are not defined. We examined the maturation phenotype and function of murine bone marrow-derived DCs infected with Langat virus (LGTV), a naturally attenuated member of the TBEV serogroup. LGTV infection failed to induce DC maturation or a cytokine response. Treatment with LPS or LPS/IFN-gamma, strong inducers of inflammatory cytokines, resulted in enhanced TNF-alpha and IL-6 production, but suppressed IL-12 production in infected DCs compared with uninfected "bystander" cells or mock-infected controls. LGTV-mediated antagonism of type I IFN (IFN-I) signaling contributed to inhibition of IL-12p40 mRNA expression at late time points after stimulation. However, early suppression was still observed in DCs lacking the IFN-I receptor (Ifnar(-/-)), suggesting that additional mechanisms of antagonism exist. The early IFN-independent inhibition of IL-12p40 was nearly abolished in DCs deficient in IFN regulatory factor-1 (IRF-1), a key transcription factor required for IL-12 production. LGTV infection did not affect Irf-1 mRNA expression, but rather diminished IRF-1 protein levels and nuclear localization. The effect on IRF-1 was also observed in DCs infected with the highly virulent Sofjin strain of TBEV. Thus, antagonism of IRF-1 is a novel mechanism that synergizes with the noted ability of flaviviruses to suppress IFN-alpha/beta receptor-dependent signaling, resulting in the orchestrated evasion of host innate immunity.
C1 [Robertson, Shelly J.; Lubick, Kirk J.; Freedman, Brett A.; Best, Sonja M.] NIAID, Innate Immun & Pathogenesis Unit, Virol Lab, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA.
[Carmody, Aaron B.] NIAID, Res Technol Branch, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
RP Best, SM (reprint author), NIAID, Virol Lab, Rocky Mt Labs, NIH, 903 South 4th St, Hamilton, MT 59840 USA.
EM sbest@niaid.nih.gov
FU National Institutes of Health, National Institute of Allergy and
Infectious Diseases
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Allergy and
Infectious Diseases.
NR 58
TC 9
Z9 9
U1 1
U2 16
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD MAR 15
PY 2014
VL 192
IS 6
BP 2744
EP 2755
DI 10.4049/jimmunol.1302110
PG 12
WC Immunology
SC Immunology
GA AC7IX
UT WOS:000332702700023
PM 24532583
ER
PT J
AU O'Connor, GM
Vivian, JP
Widjaja, JM
Bridgeman, JS
Gostick, E
Lafont, BAP
Anderson, SK
Price, DA
Brooks, AG
Rossjohn, J
McVicar, DW
AF O'Connor, Geraldine M.
Vivian, Julian P.
Widjaja, Jacqueline M.
Bridgeman, John S.
Gostick, Emma
Lafont, Bernard A. P.
Anderson, Stephen K.
Price, David A.
Brooks, Andrew G.
Rossjohn, Jamie
McVicar, Daniel W.
TI Mutational and Structural Analysis of KIR3DL1 Reveals a Lineage-Defining
Allotypic Dimorphism That Impacts Both HLA and Peptide Sensitivity
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID MHC CLASS-I; NATURAL-KILLER-CELLS; INHIBITORY RECEPTORS; NK-CELLS;
POLYMORPHISM; RECOGNITION; ALLELES; REACTIVITY; BINDING; CLONES
AB Killer Ig-like receptors (KIRs) control the activation of human NK cells via interactions with peptide-laden HLAs. KIR3DL1 is a highly polymorphic inhibitory receptor that recognizes a diverse array of HLA molecules expressing the Bw4 epitope, a group with multiple polymorphisms incorporating variants within the Bw4 motif. Genetic studies suggest that KIR3DL1 variation has functional significance in several disease states, including HIV infection. However, owing to differences across KIR3DL1 allotypes, HLA-Bw4, and associated peptides, the mechanistic link with biological outcome remains unclear. In this study, we elucidated the impact of KIR3DL1 polymorphism on peptide-laden HLA recognition. Mutational analysis revealed that KIR residues involved in water-mediated contacts with the HLA-presented peptide influence peptide binding specificity. In particular, residue 282 (glutamate) in the D2 domain underpins the lack of tolerance of negatively charged C-terminal peptide residues. Allotypic KIR3DL1 variants, defined by neighboring residue 283, displayed differential sensitivities to HLA-bound peptide, including the variable HLA-B*57:01-restricted HIV-1 Gag-derived epitope TW10. Residue 283, which has undergone positive selection during the evolution of human KIRs, also played a central role in Bw4 subtype recognition by KIR3DL1. Collectively, our findings uncover a common molecular regulator that controls HLA and peptide discrimination without participating directly in peptide-laden HLA interactions. Furthermore, they provide insight into the mechanics of interaction and generate simple, easily assessed criteria for the definition of KIR3DL1 functional groupings that will be relevant in many clinical applications, including bone marrow transplantation.
C1 [O'Connor, Geraldine M.; McVicar, Daniel W.] NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA.
[Vivian, Julian P.; Rossjohn, Jamie] Monash Univ, Sch Biomed Sci, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia.
[Widjaja, Jacqueline M.; Brooks, Andrew G.] Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3010, Australia.
[Bridgeman, John S.; Gostick, Emma; Price, David A.; Rossjohn, Jamie] Cardiff Univ, Sch Med, Inst Infect & Immun, Cardiff CF14 4XN, S Glam, Wales.
[Lafont, Bernard A. P.] NIAID, Nonhuman Primate Immunogenet & Cellular Immunol U, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Anderson, Stephen K.] Leidos Biomedical Res Inc, Basic Sci Program, Expt Immunol Lab, Frederick Natl Lab, Frederick, MD 21702 USA.
[Price, David A.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP McVicar, DW (reprint author), NCI, Bldg 560,Room 31-50, Frederick, MD 21702 USA.
EM mcvicard@mail.nih.gov
RI Price, David/C-7876-2013; McVicar, Daniel/G-1970-2015;
OI Price, David/0000-0001-9416-2737; Brooks, Andrew/0000-0002-4085-9683;
Rossjohn, Jamie/0000-0002-2020-7522
FU Intramural AIDS Targeted Antiviral Program of the National Institutes of
Health; National Health and Medical Research Council of Australia;
Association for International Cancer Research; Intramural Research
Program of the National Institutes of Health, National Cancer Institute,
National Institute of Allergy and Infectious Diseases; Frederick
National Laboratory for Cancer Research, National Institutes of Health
[HHSN26120080001E]
FX This work was supported by the Intramural AIDS Targeted Antiviral
Program of the National Institutes of Health, the National Health and
Medical Research Council of Australia, the Association for International
Cancer Research (to A. G. B. and J.R.), and the Intramural Research
Program of the National Institutes of Health, National Cancer Institute,
National Institute of Allergy and Infectious Diseases, and federal funds
from the Frederick National Laboratory for Cancer Research, National
Institutes of Health, under Contract HHSN26120080001E. J.P.V. is an
Australian Research Council Discovery Early Career Researcher Award
Fellow, D. A. P. is a Wellcome Trust Senior Investigator, and J.R. is a
National Health and Medical Research Council of Australia Fellow.
NR 43
TC 17
Z9 17
U1 0
U2 4
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD MAR 15
PY 2014
VL 192
IS 6
BP 2875
EP 2884
DI 10.4049/jimmunol.1303142
PG 10
WC Immunology
SC Immunology
GA AC7IX
UT WOS:000332702700036
PM 24563253
ER
PT J
AU Mu, J
Tai, XG
Iyer, SS
Weissman, JD
Singer, A
Singer, DS
AF Mu, Jie
Tai, Xuguang
Iyer, Shankar S.
Weissman, Jocelyn D.
Singer, Alfred
Singer, Dinah S.
TI Regulation of MHC Class I Expression by Foxp3 and Its Effect on
Regulatory T Cell Function
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; AUTOIMMUNE-DISEASE; TRANSCRIPTION FACTOR;
DNA-BINDING; COMPLEX; GENES; ENHANCEOSOME; MOLECULES; ELEMENTS; CANCER
AB Expression of MHC class I molecules, which provide immune surveillance against intracellular pathogens, is higher on lymphoid cells than on any other cell types. In T cells, this is a result of activation of class I transcription by the T cell enhanceosome consisting of Runx1, CBF beta, and LEF1. We now report that MHC class I transcription in T cells also is enhanced by Foxp3, resulting in higher levels of class I in CD4(+)CD25(+) T regulatory cells than in conventional CD4(+)CD25(-) T cells. Interestingly, the effect of Foxp3 regulation of MHC class I transcription is cell type specific: Foxp3 increases MHC class I expression in T cells but represses it in epithelial tumor cells. In both cell types, Foxp3 targets the upstream IFN response element and downstream core promoter of the class I gene. Importantly, expression of MHC class I contributes to the function of CD4(+)CD25(+) T regulatory cells by enhancing immune suppression, both in in vitro and in vivo. These findings identify MHC class I genes as direct targets of Foxp3 whose expression augments regulatory T cell function.
C1 [Mu, Jie; Tai, Xuguang; Iyer, Shankar S.; Weissman, Jocelyn D.; Singer, Alfred; Singer, Dinah S.] NCI, Expt Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Singer, DS (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10,Room 4B-36, Bethesda, MD 20892 USA.
EM Dinah.Singer@nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research.
NR 39
TC 3
Z9 3
U1 0
U2 3
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD MAR 15
PY 2014
VL 192
IS 6
BP 2892
EP 2903
DI 10.4049/jimmunol.1302847
PG 12
WC Immunology
SC Immunology
GA AC7IX
UT WOS:000332702700038
PM 24523508
ER
PT J
AU Belshe, RB
Heineman, TC
Bernstein, DI
Bellamy, AR
Ewell, M
van der Most, R
Deal, CD
AF Belshe, Robert B.
Heineman, Thomas C.
Bernstein, David I.
Bellamy, Abbie R.
Ewell, Marian
van der Most, Robbert
Deal, Carolyn D.
TI Correlate of Immune Protection Against HSV-1 Genital Disease in
Vaccinated Women
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE HSV vaccine; vaccine efficacy; protective antibodies
ID SIMPLEX-VIRUS TYPE-1; SUBUNIT VACCINE; ANTIBODY-RESPONSE; HERPES;
INFECTION; TRIAL; YOUNG
AB Background. Previously we conducted a double-blind controlled, randomized efficacy field trial of gD-2 HSV vaccine adjuvanted with ASO4 in 8323 women. Subjects had been previously selected to be seronegative for HSV-1 and HSV-2. We found that vaccine was 82% protective against HSV-1 genital disease, but offered no significant protection against HSV-2 genital disease.
Methods. To better understand the results of the efficacy study, post-vaccination anti-gD-2 antibody concentrations from all HSV infected subjects and matched uninfected controls were measured. Three models were used to determine whether these responses correlated with protection against HSV infection or disease. Similarly, cellular immune responses from a subset of subjects and matched controls were evaluated for a correlation with HSV protection.
Results. Antibodies to gD-2 correlated with protection against HSV-1 infection with higher antibody concentration associated with higher efficacy. Cellular immune responses to gD-2 did not correlate with protection.
Conclusions. The protection against HSV-1 infection observed in the Herpevac Trial for Women was associated with antibodies directed against the vaccine.
C1 [Belshe, Robert B.] St Louis Univ, Sch Med, Div Infect Dis Allergy & Immunol, Dept Internal Med, St Louis, MO 63104 USA.
[Heineman, Thomas C.; van der Most, Robbert] GlaxoSmithKline Biol, Global Clin Dev Vaccines, King Of Prussia, PA 19406 USA.
[Bernstein, David I.] Cincinnati Childrens Hosp Med Ctr, Div Infect Dis, Cincinnati, OH 45229 USA.
[Bellamy, Abbie R.; Ewell, Marian] EMMES Corp, Rockville, MD 20850 USA.
[Deal, Carolyn D.] NIAID, Dept Hlth & Human Serv, NIH, DMID,STDB, Bethesda, MD 20892 USA.
RP Belshe, RB (reprint author), St Louis Univ, Sch Med, Div Infect Dis Allergy & Immunol, 1100 S Grand Blvd,DRC 8, St Louis, MO 63104 USA.
EM belsherb@slu.edu
FU National Institute of Allergy and Infectious Diseases [N01-AI-45250];
GlaxoSmithKline
FX This research was supported by a contract with the National Institute of
Allergy and Infectious Diseases (N01-AI-45250) and by GlaxoSmithKline.
NR 10
TC 30
Z9 30
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD MAR 15
PY 2014
VL 209
IS 6
BP 828
EP 836
DI 10.1093/infdis/jit651
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA AC2PH
UT WOS:000332343600004
PM 24285844
ER
PT J
AU Wentzensen, N
Nason, M
Schiffman, M
Dodd, L
Hunt, WC
Wheeler, CM
AF Wentzensen, Nicolas
Nason, Martha
Schiffman, Mark
Dodd, Lori
Hunt, William C.
Wheeler, Cosette M.
CA New Mexico HPV Pap Registry Steeri
TI No Evidence for Synergy Between Human Papillomavirus Genotypes for the
Risk of High-Grade Squamous Intraepithelial Lesions in a Large
Population-Based Study
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE cervical cancer screening; cytology; human papillomavirus (HPV);
multiple Infections
ID CERVICAL-CANCER; MULTIPLE TYPES; UNITED-STATES; NEOPLASIA; INFECTION;
WOMEN; VACCINATION; AGE
AB Background. Multiple human papillomavirus (HPV) genotypes may be independently or synergistically associated with risk of high-grade squamous intraepithelial lesions (HSILs). We evaluated the risk of HSIL in women concomitantly infected with multiple HPV genotypes.
Methods. A population-based stratified sample of 59 664 cervical cytology specimens from women residing in New Mexico were evaluated for cytologic abnormalities and HPV genotypes. We calculated the risk of HSIL in women infected with a single HPV genotype and the risk in those infected with multiple HPV genotypes.
Results. The highest risk of HSIL was observed for HPV-16 (0.036), followed by HPV-33 (0.028), HPV-58 (0.024), and HPV-18 (0.022). For most types, we observed a greater risk of HSIL in women infected with multiple carcinogenic HPV types. In contrast, the risk of HSIL was similar in women infected with HPV-16 and other types, compared with women infected with HPV-16 only. We observed an increased but plateauing risk of HSIL in women infected with multiple types, compared with those infected with a single type, with risk ratios of 1.5 (95% confidence interval [CI], 1.2-1.8), 1.7 (95% CI, 1.3-2.4), and 1.4 (95% CI, 0.83-2.5) for women infected with 2, 3, and >= 4 genotypes, respectively.
Conclusions. In the largest population-based study of HPV genotypes and cytologic outcomes so far, we did not see more than additive effects of HPV types on the risk of HSIL in women infected with multiple types.
C1 [Wentzensen, Nicolas; Schiffman, Mark] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Nason, Martha; Dodd, Lori] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
[Hunt, William C.; Wheeler, Cosette M.] Univ New Mexico, Dept Pathol, Hlth Sci Ctr, Albuquerque, NM 87131 USA.
RP Wheeler, CM (reprint author), Univ New Mexico, Dept Pathol, Hlth Sci Ctr, House Prevent Epidemiol HOPE Bldg 191, Albuquerque, NM 87131 USA.
EM cwheeler@salud.unm.edu
FU National Institutes of Health [U19AI084081, R01CA134779]; National
Cancer Institute; National Institute of Allergy and Infectious Diseases,
National Institutes of Health, Department of Health and Human Services
FX This work was supported by the National Institutes of Health (awards
U19AI084081 and R01CA134779 to C.M.W.) and by the Intramural Research
Programs of the National Cancer Institute and National Institute of
Allergy and Infectious Diseases, National Institutes of Health,
Department of Health and Human Services. HPV Linear Array reagents and
equipment to automate HPV genotyping assays were provided by Roche
Molecular Systems.
NR 17
TC 9
Z9 12
U1 0
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD MAR 15
PY 2014
VL 209
IS 6
BP 855
EP 864
DI 10.1093/infdis/jit577
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA AC2PH
UT WOS:000332343600007
PM 24179110
ER
PT J
AU Krishnan, S
Wilson, EMP
Sheikh, V
Rupert, A
Mendoza, D
Yang, J
Lempicki, R
Migueles, SA
Sereti, I
AF Krishnan, Sonya
Wilson, Eleanor M. P.
Sheikh, Virginia
Rupert, Adam
Mendoza, Daniel
Yang, Jun
Lempicki, Richard
Migueles, Stephen A.
Sereti, Irini
TI Evidence for Innate Immune System Activation in HIV Type 1-Infected
Elite Controllers
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE HIV; Elite Controllers; Biomarkers; D-dimer; soluble Tissue Factor;
Monocytes
ID INCIDENT CARDIOVASCULAR-DISEASE; LONG-TERM NONPROGRESSORS;
CORONARY-HEART-DISEASE; CD8(+) T-CELLS; ANTIRETROVIRAL THERAPY; D-DIMER;
MYOCARDIAL-INFARCTION; TISSUE FACTOR; CLINICAL-IMPLICATIONS; INFECTED
INDIVIDUALS
AB Background. Elite controllers maintain high CD4(+) T-cell counts and suppress plasma human immunodeficiency virus (HIV) viremia in the absence of antiretroviral therapy (ART). It is unclear whether levels of biomarkers associated with coagulation, monocyte activation, and inflammation, which are linked to HIV-associated mortality, differ among elite controllers, ART recipients with suppressed viremia (plasma HIV type 1 RNA load, <50 copies/mL), and HIV-negative controls.
Methods. A total of 68 elite controllers, 68 ART recipients with suppressed viremia, and 35 HIV-negative participants were evaluated. Levels of biomarkers in cryopreserved plasma were measured by enzyme-linked immunosorbent assay and electrochemiluminescence-based assay. Cryopreserved peripheral blood mononuclear cells were used to assess monocyte phenotype and function and interferon-inducible gene expression (IFIG). Nonparametric testing was used to compare median values among groups.
Results. CD4(+) T-cell counts were similar between elite controllers and HIV-negative controls but significantly lower in ART recipients with suppressed viremia. Levels of C-reactive protein and interleukin 6 were higher and IFIG upregulated in both HIV-positive groups, compared with HIV-negative controls. D-dimer and soluble tissue factor levels were significantly elevated in elite controllers, compared with those in ART recipients with suppressed viremia and HIV-negative controls (P < .01). Monocytes from elite controllers (and ART recipients with suppressed viremia) expressed lower CCR2 and higher CX3CR1 levels than monocytes from HIV-negative controls. In addition, elite controllers had a significantly higher proportion of CD14(+)CD16(+) monocytes, compared with HIV-negative controls.
Conclusion. Elite controllers maintain control of plasma HIV viremia and have evidence of an activated innate immune response.
C1 [Krishnan, Sonya] NCI, Clin Res Directorate, Clin Monitoring Res Program, Frederick, MD 21701 USA.
[Rupert, Adam] NCI, AIDS Monitoring Lab, Frederick, MD 21701 USA.
[Yang, Jun; Lempicki, Richard] NCI, Appl & Dev Res Directorate, Sci Applicat Int Corp SAIC Frederick, Frederick, MD 21701 USA.
[Wilson, Eleanor M. P.; Sheikh, Virginia; Mendoza, Daniel; Migueles, Stephen A.; Sereti, Irini] NIAID, NIH, Bethesda, MD 20892 USA.
RP Sereti, I (reprint author), NIH, 10 Ctr Dr,Bldg 10,Rm 11B07A, Bethesda, MD 20892 USA.
EM isereti@niaid.nih.gov
RI Lempicki, Richard/E-1844-2012;
OI Lempicki, Richard/0000-0002-7059-409X; Mendoza,
Daniel/0000-0002-6362-0771; Wilson, Eleanor/0000-0002-4855-514X
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; Intramural Research Program, National Institute of
Allergy and Infectious Diseases
FX This work was supported by the National Cancer Institute, National
Institutes of Health (contract HHSN261200800001E), and the Intramural
Research Program, National Institute of Allergy and Infectious Diseases.
NR 50
TC 44
Z9 44
U1 0
U2 11
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD MAR 15
PY 2014
VL 209
IS 6
BP 931
EP 939
DI 10.1093/infdis/jit581
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA AC2PH
UT WOS:000332343600015
PM 24185941
ER
PT J
AU Drinkwater, DC
Davidson-Moncada, J
Heckendorn, E
Myers, J
Whitman, TJ
AF Drinkwater, Dennis C.
Davidson-Moncada, Jan
Heckendorn, Emily
Myers, Janet
Whitman, Timothy J.
TI A Patient With Ulcerated Nodules on His Face
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Editorial Material
ID PROLONGED VORICONAZOLE THERAPY; SQUAMOUS-CELL CARCINOMAS; TRIAZOLE
ANTIFUNGAL AGENT; PHOTOSENSITIVITY
C1 [Drinkwater, Dennis C.] Walter Reed Natl Mil Med Ctr, Dept Internal Med, Bethesda, MD 20889 USA.
[Davidson-Moncada, Jan] NIH, Dept Hematol Oncol, Bethesda, MD 20892 USA.
[Heckendorn, Emily] Walter Reed Natl Mil Med Ctr, Dept Pathol, Bethesda, MD 20889 USA.
[Myers, Janet] US Naval Hosp Okinawa, Dept Pulm Med, Nakagami, Japan.
[Whitman, Timothy J.] Walter Reed Natl Mil Med Ctr, Dept Infect Dis, Bethesda, MD 20889 USA.
RP Whitman, TJ (reprint author), Walter Reed Natl Mil Med Ctr, Dept Infect Dis, 8901 Wisconsin Ave, Bethesda, MD 20889 USA.
EM timothy.j.whitman.mil@health.mil
NR 12
TC 0
Z9 0
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
EI 1537-6591
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD MAR 15
PY 2014
VL 58
IS 6
BP 839
EP +
DI 10.1093/cid/cit716
PG 3
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA AC2KQ
UT WOS:000332330200016
PM 24573080
ER
PT J
AU Ketley, A
Chen, CZ
Li, X
Arya, S
Robinson, TE
Granados-Riveron, J
Udosen, I
Morris, GE
Holt, I
Furling, D
Chaouch, S
Haworth, B
Southall, N
Shinn, P
Zheng, W
Austin, CP
Hayes, CJ
Brook, JD
AF Ketley, Ami
Chen, Catherine Z.
Li, Xin
Arya, Sukrat
Robinson, Thelma E.
Granados-Riveron, Javier
Udosen, Inyang
Morris, Glenn E.
Holt, Ian
Furling, Denis
Chaouch, Soraya
Haworth, Ben
Southall, Noel
Shinn, Paul
Zheng, Wei
Austin, Christopher P.
Hayes, Christopher J.
Brook, J. David
TI High-content screening identifies small molecules that remove nuclear
foci, affect MBNL distribution and CELF1 protein levels via a
PKC-independent pathway in myotonic dystrophy cell lines
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID EXPANDED-REPEAT TRANSCRIPTS; 3 UNTRANSLATED REGION; MUSCULAR-DYSTROPHY;
TRIPLET-REPEAT; MESSENGER-RNA; IN-VIVO; TRINUCLEOTIDE REPEAT; RATIONAL
DESIGN; SKELETAL-MUSCLE; CTG REPEAT
AB Myotonic dystrophy (DM) is a multi-system neuromuscular disorder for which there is no treatment. We have developed a medium throughput phenotypic assay, based on the identification of nuclear foci in DM patient cell lines using in situ hybridization and high-content imaging to screen for potentially useful therapeutic compounds. A series of further assays based on molecular features of DM have also been employed. Two compounds that reduce and/or remove nuclear foci have been identified, Ro 31-8220 and chromomycin A3. Ro 31-8220 is a PKC inhibitor, previously shown to affect the hyperphosphorylation of CELF1 and ameliorate the cardiac phenotype in a DM1 mouse model. We show that the same compound eliminates nuclear foci, reduces MBNL1 protein in the nucleus, affects ATP2A1 alternative splicing and reduces steady-state levels of CELF1 protein. We demonstrate that this effect is independent of PKC activity and conclude that this compound may be acting on alternative kinase targets within DM pathophysiology. Understanding the activity profile for this compound is key for the development of targeted therapeutics in the treatment of DM.
C1 [Ketley, Ami; Li, Xin; Arya, Sukrat; Robinson, Thelma E.; Granados-Riveron, Javier; Udosen, Inyang; Brook, J. David] Univ Nottingham, Queens Med Ctr, Sch Life Sci, Nottingham NG7 2UH, England.
[Chen, Catherine Z.; Southall, Noel; Shinn, Paul; Zheng, Wei; Austin, Christopher P.; Hayes, Christopher J.] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
[Morris, Glenn E.; Holt, Ian] RJAH Orthopaed Hosp, Wolfson Ctr Inherited Neuromuscular Dis, Oswestry SY10 7AG, Shrops, England.
[Morris, Glenn E.; Holt, Ian] Keele Univ, Inst Sci & Technol Med, Keele, Staffs, England.
[Furling, Denis; Chaouch, Soraya] Univ Paris 06, UM 76, Inst Myol, F-75013 Paris, France.
[Furling, Denis; Chaouch, Soraya] INSERM, U974, F-75013 Paris, France.
[Furling, Denis; Chaouch, Soraya] CNRS, UMR7215, F-75013 Paris, France.
[Haworth, Ben] Mol Devices, Wokingham RG41 5TS, Berks, England.
[Hayes, Christopher J.] Univ Nottingham, Sch Chem, Nottingham NG7 2RD, England.
RP Brook, JD (reprint author), Univ Nottingham, Queens Med Ctr, Sch Life Sci, Nottingham NG7 2UH, England.
EM david.brook@nottingham.ac.uk
RI Southall, Noel/H-8991-2012; Hayes, Christopher/B-6022-2016; Zheng,
Wei/J-8889-2014;
OI Southall, Noel/0000-0003-4500-880X; Hayes,
Christopher/0000-0003-1692-3646; Zheng, Wei/0000-0003-1034-0757;
Granados-Riveron, Javier T./0000-0002-0368-225X; Brook, John
David/0000-0002-5946-6740
FU MRC DPFS; Muscular Dystrophy Campaign; Leverhulme Trust; Myotonic
Dystrophy Support Group; Association Francaise contre les Myopathies;
Marigold Foundation Research fellowship for CZC; Medical Research
Council; intramural research of the National Centre for Advancing
Translational Sciences, NIH
FX This research was funded by an MRC DPFS award, the Muscular Dystrophy
Campaign, the Leverhulme Trust, the Myotonic Dystrophy Support Group,
the Association Francaise contre les Myopathies, intramural research of
the National Centre for Advancing Translational Sciences, NIH, and a
Marigold Foundation Research fellowship for CZC. Funding to pay the Open
Access publication charges for this article was provided by the Medical
Research Council.
NR 50
TC 13
Z9 14
U1 0
U2 16
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD MAR 15
PY 2014
VL 23
IS 6
BP 1551
EP 1562
DI 10.1093/hmg/ddt542
PG 12
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA AB8MK
UT WOS:000332044300013
PM 24179176
ER
PT J
AU Lai, YL
Albert, PS
AF Lai, Yinglei
Albert, Paul S.
TI Identifying multiple change points in a linear mixed effects model
SO STATISTICS IN MEDICINE
LA English
DT Article
DE change point; longitudinal data; linear mixed effects model;
expectation-maximization algorithm; dynamic programming algorithm
ID LONGITUDINAL DATA; SEGMENTATION
AB Although change-point analysis methods for longitudinal data have been developed, it is often of interest to detect multiple change points in longitudinal data. In this paper, we propose a linear mixed effects modeling framework for identifying multiple change points in longitudinal Gaussian data. Specifically, we develop a novel statistical and computational framework that integrates the expectation-maximization and the dynamic programming algorithms. We conduct a comprehensive simulation study to demonstrate the performance of our method. We illustrate our method with an analysis of data from a trial evaluating a behavioral intervention for the control of type I diabetes in adolescents with HbA1c as the longitudinal response variable. Copyright (c) 2013 John Wiley & Sons, Ltd.
C1 [Lai, Yinglei] George Washington Univ, Dept Stat, Washington, DC 20052 USA.
[Lai, Yinglei] George Washington Univ, Ctr Biostat, Washington, DC 20052 USA.
[Albert, Paul S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Epidemiol Stat & Prevent Res, Rockville, MD 20852 USA.
RP Lai, YL (reprint author), George Washington Univ, Dept Stat, Rome Hall,Room 553,801 22nd St NW, Washington, DC 20052 USA.
EM ylai@gwu.edu
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development of the National
Institute of Health; National Institute of General Medical Sciences of
the National Institutes of Health [R01GM092963]
FX This research was partially supported by the Intramural Research Program
of the Eunice Kennedy Shriver National Institute of Child Health and
Human Development of the National Institute of Health. Research reported
in this publication was also partially supported by the National
Institute of General Medical Sciences of the National Institutes of
Health under Award Number R01GM092963 (to Y.L.). The content is solely
the responsibility of the authors and does not necessarily represent the
official views of the National Institutes of Health.
NR 23
TC 1
Z9 1
U1 0
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-6715
EI 1097-0258
J9 STAT MED
JI Stat. Med.
PD MAR 15
PY 2014
VL 33
IS 6
BP 1015
EP 1028
DI 10.1002/sim.5996
PG 14
WC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Medicine, Research &
Experimental; Statistics & Probability
SC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Research & Experimental
Medicine; Mathematics
GA AA9DZ
UT WOS:000331395300009
PM 24114935
ER
PT J
AU Cornwell, BR
Overstreet, C
Grillon, C
AF Cornwell, B. R.
Overstreet, C.
Grillon, C.
TI Spontaneous fast gamma activity in the septal hippocampal region
correlates with spatial learning in humans
SO BEHAVIOURAL BRAIN RESEARCH
LA English
DT Article
DE Gamma activity; Hippocampus; Magnetoencephalography; Memory
consolidation; Spatial learning; Virtual reality
ID HIGH-FREQUENCY OSCILLATIONS; MEDIAL TEMPORAL-LOBE; VIRTUAL WATER MAZE;
THETA-RHYTHM; MEMORY CONSOLIDATION; HUMAN CORTEX; NAVIGATION; RIPPLES;
BRAIN; MAGNETOENCEPHALOGRAPHY
AB Hippocampal neuronal populations exhibit multiple kinds of activity patterns, from the dominant theta rhythm during active exploration to high-frequency ripple-like activity during periods of relative inactivity. In animals, evidence is rapidly accruing that these high-frequency ripple activity patterns subserve retention of spatial learning performance. In a translational effort to address the possible function of offline hippocampal processes in humans, we measured spontaneous gamma activity during an awake rest period within a virtual spatial learning context. Whole-head magnetoencephalographic (MEG) recordings were taken while healthy participants (N=24) quietly rested (eyes open) between encoding and retrieval phases of a hippocampal-dependent virtual Morris water maze task. Results are that fast gamma activity (80-140 Hz) in the septal or posterior region of the hippocampus (bilaterally) was positively correlated across participants with subsequent within-session spatial learning rate. Fast gamma did not predict initial retrieval performance following rest, failing to provide evidence of a direct link between spontaneous high-frequency activity patterns during awake rest and consolidation of previous spatial memories. The findings nevertheless are consistent with a prospective role for offline human hippocampal processes in spatial learning and indicate that higher spontaneous gamma activity in the septal hippocampal region is related to faster updating of spatial knowledge in familiar virtual surroundings. Published by Elsevier B.V.
C1 [Cornwell, B. R.] Swinburne Univ Technol, Brain & Psychol Sci Res Ctr, Hawthorn, Vic 3122, Australia.
[Cornwell, B. R.; Overstreet, C.; Grillon, C.] NIMH, Sect Neurobiol Fear & Anxiety, NIH, Bethesda, MD 20892 USA.
RP Cornwell, BR (reprint author), Swinburne Univ Technol, Mail H99,POB 218, Hawthorn, Vic 3122, Australia.
EM bcornwell@swin.edu.au
FU National Institute of Mental Health
FX This work was funded by the Intramural Research Program of the National
Institute of Mental Health.
NR 45
TC 1
Z9 1
U1 0
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-4328
EI 1872-7549
J9 BEHAV BRAIN RES
JI Behav. Brain Res.
PD MAR 15
PY 2014
VL 261
BP 258
EP 264
DI 10.1016/j.bbr.2013.12.031
PG 7
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA AB0QK
UT WOS:000331497000032
PM 24388977
ER
PT J
AU Bai, RL
Basser, PJ
Briber, RM
Horkay, F
AF Bai, Ruiliang
Basser, Peter J.
Briber, Robert M.
Horkay, Ferenc
TI NMR Water Self- Diffusion and Relaxation Studies on Sodium Polyacrylate
Solutions and Gels in Physiologic Ionic Solutions
SO JOURNAL OF APPLIED POLYMER SCIENCE
LA English
DT Article
ID MOLECULAR-DYNAMICS SIMULATIONS; NUCLEAR-MAGNETIC-RESONANCE; POLYMER
SOLVENT SYSTEMS; SPIN-LATTICE RELAXATION; FREE-VOLUME THEORIES;
SINGLE-SIDED NMR; HYDRATION WATER; TRANSVERSE RELAXATION;
STRUCTURAL-CHANGES; PROTON RELAXATION
C1 [Bai, Ruiliang; 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.
[Bai, Ruiliang] Univ Maryland, Inst Phys Sci & Technol, Biophys Program, College Pk, MD 20740 USA.
[Briber, Robert M.] Univ Maryland, Dept Mat Sci & Engn, College Pk, MD 20740 USA.
RP Bai, RL (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 ruiliang.bai@nih.gov
RI Briber, Robert/A-3588-2012
OI Briber, Robert/0000-0002-8358-5942
FU Intramural Research Program of the NICHD, NIH
FX This research was supported by the Intramural Research Program of the
NICHD, NIH. We thank the comments from Dr. Uzi Eliav (Tel Aviv
University).
NR 67
TC 8
Z9 8
U1 3
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0021-8995
EI 1097-4628
J9 J APPL POLYM SCI
JI J. Appl. Polym. Sci.
PD MAR 15
PY 2014
VL 131
IS 6
AR 40001
DI 10.1002/app.40001
PG 7
WC Polymer Science
SC Polymer Science
GA AA3PM
UT WOS:000331004800017
ER
PT J
AU Kroesen, M
Nierkens, S
Ansems, M
Wassink, M
Orentas, RJ
Boon, L
den Brok, MH
Hoogerbrugge, PM
Adema, GJ
AF Kroesen, Michiel
Nierkens, Stefan
Ansems, Marleen
Wassink, Melissa
Orentas, Rimas J.
Boon, Louis
den Brok, Martijn H.
Hoogerbrugge, Peter M.
Adema, Gosse J.
TI A transplantable TH-MYCN transgenic tumor model in C57Bl/6 mice for
preclinical immunological studies in neuroblastoma
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE neuroblastoma; immunotherapy; autologous mouse model; anti-GD2 mAb
therapy; NK cell
ID HIGH-RISK NEUROBLASTOMA; STEM-CELL TRANSPLANTATION; VACCINE-INDUCED
IMMUNITY; ANTI-GD2 ANTIBODY; DENDRITIC CELLS; IMMUNOTHERAPEUTIC
IMPLICATIONS; MURINE NEUROBLASTOMA; BONE-MARROW; CLASS-I; EXPRESSION
AB Current multimodal treatments for patients with neuroblastoma (NBL), including anti-disialoganglioside (GD2) monoclonal antibody (mAb) based immunotherapy, result in a favorable outcome in around only half of the patients with advanced disease. To improve this, novel immunocombinational strategies need to be developed and tested in autologous preclinical NBL models. A genetically well-explored autologous mouse model for NBL is the TH-MYCN model. However, the immunobiology of the TH-MYCN model remains largely unexplored. We developed a mouse model using a transplantable TH-MYCN cell line in syngeneic C57Bl/6 mice and characterized the immunobiology of this model. In this report, we show the relevance and opportunities of this model to study immunotherapy for human NBL. Similar to human NBL cells, syngeneic TH-MYCN-derived 9464D cells endogenously express the tumor antigen GD2 and low levels of MHC Class I. The presence of the adaptive immune system had little or no influence on tumor growth, showing the low immunogenicity of the NBL cells. In contrast, depletion of NK1.1+ cells resulted in enhanced tumor outgrowth in both wild-type and Rag1(-/-) mice, showing an important role for NK cells in the natural anti-NBL immune response. Analysis of the tumor infiltrating leukocytes ex vivo revealed the presence of both tumor associated myeloid cells and T regulatory cells, thus mimicking human NBL tumors. Finally, anti-GD2 mAb mediated NBL therapy resulted in ADCC in vitro and delayed tumor outgrowth in vivo. We conclude that the transplantable TH-MYCN model represents a relevant model for the development of novel immunocombinatorial approaches for NBL patients.
What's new? Natural killer (NK) cells may serve a role in immune defense against neuroblastoma, though limitations in existing models have prevented extensive study of the immunological characteristics of the disease. Here, to better understand the immunobiology of neuroblastoma, the TH-MYCN mouse model was adapted for immunological investigation. Tumor cells (9464D) derived from immunologically compatible C57Bl/6 TH-MYCN mice were found to express the tumor antigen GD2. In addition, depletion of NK cells was associated with tumor outgrowth in both wild-type and Rag1-/- C57Bl/6 mice, whereas immunotherapy targeted against GD2 decreased tumor growth.
C1 [Kroesen, Michiel; Nierkens, Stefan; Ansems, Marleen; Wassink, Melissa; den Brok, Martijn H.; Adema, Gosse J.] Radboud Univ Nijmegen, Med Ctr, Nijmegen Ctr Mol Life Sci, Dept Tumor Immunol, NL-6525 ED Nijmegen, Netherlands.
[Kroesen, Michiel; Hoogerbrugge, Peter M.] Radboud Univ Nijmegen, Nijmegen Med Ctr, Dept Pediat Oncol, NL-6525 ED Nijmegen, Netherlands.
[Nierkens, Stefan] Univ Med Ctr Utrecht, Utrecht Ctr Diagnost Adv Immunol Res U DAIR, Dept Immunol, Utrecht, Netherlands.
[Orentas, Rimas J.] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Boon, Louis] Bioceros BV, Utrecht, Netherlands.
RP Adema, GJ (reprint author), Nijmegen Ctr Mol Life Sci 278 TIL, Dept Tumor Immunol, Post Box 9101, NL-6500 HB Nijmegen, Netherlands.
EM g.adema@ncmls.ru.nl
RI Adema, G.J./H-8007-2014; Hoogerbrugge, Peter/H-8049-2014; den Brok,
Martijn/O-1054-2013
FU Vrienden KOC Nijmegen, Villa Joep Foundation
FX Grant sponsor: Vrienden KOC Nijmegen, Villa Joep Foundation
NR 47
TC 9
Z9 9
U1 0
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
EI 1097-0215
J9 INT J CANCER
JI Int. J. Cancer
PD MAR 15
PY 2014
VL 134
IS 6
BP 1335
EP 1345
DI 10.1002/ijc.28463
PG 11
WC Oncology
SC Oncology
GA 283CS
UT WOS:000329223000008
PM 24038106
ER
PT J
AU Ryan, BM
Zanetti, KA
Robles, AI
Schetter, AJ
Goodman, J
Hayes, RB
Huang, WY
Gunter, MJ
Yeager, M
Burdette, L
Berndt, SI
Harris, CC
AF Ryan, Brid M.
Zanetti, Krista A.
Robles, Ana I.
Schetter, Aaron J.
Goodman, Julie
Hayes, Richard B.
Huang, Wen-Yi
Gunter, Mark J.
Yeager, Meredith
Burdette, Laurie
Berndt, Sonja I.
Harris, Curtis C.
TI Germline variation in NCF4, an innate immunity gene, is associated with
an increased risk of colorectal cancer
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE colorectal cancer; single nucleotide polymorphism; innate immunity; NCF4
ID INFLAMMATORY-BOWEL-DISEASE; POPULATION-BASED COHORT; GENOME-WIDE
ASSOCIATION; PERIANAL CROHNS-DISEASE; SUSCEPTIBILITY LOCI; NADPH
OXIDASE; COLON-CANCER; ULCERATIVE-COLITIS; ADVANCED ADENOMAS;
METAANALYSIS
AB Chronic inflammation has been implicated in the etiology of colorectal adenoma and cancer; however, few key inflammatory genes mediating this relationship have been identified. In this study, we investigated the association of germline variation in innate immunity genes in relation to the risk of colorectal neoplasia. Our study was based on the analysis of samples collected from the prostate, lung, colorectal and ovarian (PLCO) Cancer Screening Trial. We investigated the association between 196 tag single nucleotide polymorphisms (SNPs) in 20 key innate immunity genes with risk of advanced colorectal adenoma and cancer in 719 adenoma cases, 481 cancer cases and 719 controls. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CIs). After Bonferroni correction, the AG/GG genotype of rs5995355, which is upstream of NCF4, was associated with an increased risk of colorectal cancer (OR=2.43, 95% CI=1.73-3.39; p<0.0001). NCF4 is part of the NAPDH complex, a key factor in biochemical pathways and the innate immune response. While not definitive, our analyses suggest that the variant allele does not affect expression of NCF4, but rather modulates activity of the NADPH complex. Additional studies on the functional consequences of rs5995355 in NCF4 may help to clarify the mechanistic link between inflammation and colorectal cancer.
What's new? A single nucleotide polymorphism (SNP) known as rs5995355 in the gene NCF4, a member of the NADPH oxidase complex, is associated with increased risk of inflammatory bowel disease. The NADPH system functions in the elimination of invading microorganisms and has never previously been linked to colorectal cancer. As this screen for colorectal adenoma and cancer-related gene variants reveals, however, the NCF4 germline SNP may share a unique association with colon cancer. The analysis suggests that the variant disrupts the functionality of the NADPH complex, possibly impeding the ability of neutrophils to repel infectious agents.
C1 [Ryan, Brid M.; Zanetti, Krista A.; Robles, Ana I.; Schetter, Aaron J.; Harris, Curtis C.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Zanetti, Krista A.] Div Canc Control & Populat Sci, Host Susceptibil Factors Branch, Epidemiol & Genom Res Program, Rockville, MD 20852 USA.
[Goodman, Julie] Gradient Corp, Cambridge, MA 02138 USA.
[Hayes, Richard B.] NYU, Langone Med Ctr, Inst Canc, Div Epidemiol,Dept Environm Med, New York, NY 10016 USA.
[Huang, Wen-Yi; Berndt, Sonja I.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
[Gunter, Mark J.] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London W2 1PG, England.
[Yeager, Meredith; Burdette, Laurie] ATC, Core Genotyping Facil, Gaithersburg, MD 20877 USA.
RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, Bldg 37,Room 3068,37 Convent Dr,MSC 4258, Bethesda, MD 20892 USA.
EM curtis_harris@nih.gov
OI Hayes, Richard/0000-0002-0918-661X
FU Center for Cancer Research; Division of Cancer Epidemiology and Genetics
FX Grant sponsor: Center for Cancer Research and Division of Cancer
Epidemiology and Genetics
NR 48
TC 9
Z9 9
U1 2
U2 28
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
EI 1097-0215
J9 INT J CANCER
JI Int. J. Cancer
PD MAR 15
PY 2014
VL 134
IS 6
BP 1399
EP 1407
DI 10.1002/ijc.28457
PG 9
WC Oncology
SC Oncology
GA 283CS
UT WOS:000329223000014
PM 23982929
ER
PT J
AU Poliakov, E
Strunnikova, NV
Jiang, JK
Martinez, B
Parikh, T
Lakkaraju, A
Thomas, C
Brooks, BP
Redmond, TM
AF Poliakov, Eugenia
Strunnikova, Natalya V.
Jiang, Jian-kang
Martinez, Bianca
Parikh, Toral
Lakkaraju, Aparna
Thomas, Craig
Brooks, Brian P.
Redmond, T. Michael
TI Multiple A2E treatments lead to melanization of rod outer
segment-challenged ARPE-19 cells
SO MOLECULAR VISION
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; RETINYLIDENE-N-RETINYLETHANOLAMINE; MACULAR
DEGENERATION; FUNDUS AUTOFLUORESCENCE; LIPOFUSCIN FLUOROPHORE; RPE
CELLS; GEOGRAPHIC ATROPHY; MOUSE MODEL; MELANIN; ACCUMULATION
AB Purpose: Daily phagocytosis of outer segments (OSs) and retinoid recycling by the RPE lead to the accumulation of storage bodies in the RPE containing autofluorescent lipofuscin, which consists of lipids and bisretinoids such as A2E and its oxidation products. Accumulation of A2E and its oxidation products is implicated in the pathogenesis of several retinal degenerative diseases. However, A2E accumulates in the RPE during normal aging. In this study, we used a cell model to determine the homeostatic mechanisms of RPE cells in response to A2E accumulation.
Methods: To distinguish between pathologic and normal responses of the RPE to A2E accumulation, we treated established ARPE-19 cells (cultured for 3 weeks after reaching confluence) with low micromolar amounts of A2E for several weeks. We compared the lysosomal function, lysosomal pH, degree of OS digestion, and melanization of the treated cells to untreated control cells in response to a challenge of purified rod OSs (ROSs). A2E was analyzed with high-performance liquid chromatography (HPLC); and A2E and melanin were identified with mass spectrometry.
Results: We found that post-confluent ARPE-19 cells took up and accumulated A2E under dim light conditions. Spectral analysis of the HPLC separations and mass spectrometry showed that A2E-fed cells contained A2E and oxidized A2E (furan-A2E). A2E accumulation led to a modest increase (up to 0.25 unit) in lysosomal pH in these cells. The specific activity of cathepsin D and lysosomal acid phosphatase was reduced in the A2E-treated cells, but ROS degradation was not impaired. We found that, upon challenge with ROSs, melanin pigment was induced in the lysosomal fraction of the A2E-treated ARPE-19 cells. Thus, the ARPE-19 cells responded to the A2E treatment and ROS challenge by producing a melanin-containing lysosome fraction. We speculate that this prevents them from becoming impaired in OS processing.
Conclusions: We used a modified ARPE-19 cell model in which melanization was elicited as a response to chronic accumulation of A2E. We found that although A2E treatment led, as has been previously reported, to modest lysosomal alkalinization and lysosomal impairment of ARPE-19 cells, a potential homeostatic mechanism may involve production of a special type of lysosomes containing melanin.
C1 [Poliakov, Eugenia; Martinez, Bianca; Parikh, Toral; Redmond, T. Michael] NEI, Lab Retinal Cell & Mol Biol, NIH, Bethesda, MD 20892 USA.
[Strunnikova, Natalya V.; Brooks, Brian P.] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
[Jiang, Jian-kang; Thomas, Craig] NIH, Chem Genom Ctr, Natl Ctr Adv Translat Sci, Rockville, MD USA.
[Lakkaraju, Aparna] Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI USA.
RP Redmond, TM (reprint author), NEI, LRCMB, NIH, Bldg 6,Rm 117A,6 Ctr Dr MSC 0608, Bethesda, MD 20892 USA.
EM redmondd@helix.nih.gov
OI Redmond, T. Michael/0000-0002-1813-5291
FU Intramural Research Program of the National Eye Institute; National
Center for Advancing Translational Sciences, National Institutes of
Health; Howard Hughes Medical Institute
FX This research was supported by the Intramural Research Program of the
National Eye Institute, and of the National Center for Advancing
Translational Sciences, National Institutes of Health. T.P. was
supported by the Howard Hughes Medical Institute. We thank Dr. Robert N.
Fariss and Dr. Maria M. Campos, Biological Imaging Core, NEI for
assisting with confocal microscopy.
NR 63
TC 6
Z9 7
U1 1
U2 2
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 MAR 14
PY 2014
VL 20
BP 285
EP 300
PG 16
WC Biochemistry & Molecular Biology; Ophthalmology
SC Biochemistry & Molecular Biology; Ophthalmology
GA AK3CV
UT WOS:000338301400001
PM 24644403
ER
PT J
AU Abeykoon, A
Wang, GH
Chao, CC
Chock, PB
Gucek, M
Ching, WM
Yang, DCH
AF Abeykoon, Amila
Wang, Guanghui
Chao, Chien-Chung
Chock, P. Boon
Gucek, Marjan
Ching, Wei-Mei
Yang, David C. H.
TI Multimethylation of Rickettsia OmpB Catalyzed by Lysine
Methyltransferases
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Bacteria; Cell Surface Protein; Enzyme Catalysis; Mass Spectrometry
(MS); Protein Methylation
ID OUTER-MEMBRANE-PROTEIN; PROTEOMIC ANALYSIS; METHYLATION; PROWAZEKII;
INFECTION; TYPHI; TRIMETHYLLYSINE; RECOGNITION; ANTIGENS; INVASION
AB Background: Methylation of OmpB has been implicated in rickettsial virulence. Results: Native OmpBs purified from Rickettsia contain mono- and trimethyllysine at specific locations that coincide with those catalyzed by methyltransferases in vitro. Conclusion: The number of trimethyllysine clusters in OmpBs correlates with degree of virulence. Significance: This study provides new insight into methylation of OmpB and its correlation with virulence.
Methylation of rickettsial OmpB (outer membrane protein B) has been implicated in bacterial virulence. Rickettsial methyltransferases RP789 and RP027-028 are the first biochemically characterized methyltransferases to catalyze methylation of outer membrane protein (OMP). Methylation in OMP remains poorly understood. Using semiquantitative integrated liquid chromatography-tandem mass spectroscopy, we characterize methylation of (i) recombinantly expressed fragments of Rickettsia typhi OmpB exposed in vitro to trimethyltransferases of Rickettsia prowazekii RP027-028 and of R. typhi RT0101 and to monomethyltransferases of R. prowazekii RP789 and of R. typhi RT0776, and (ii) native OmpBs purified from R. typhi and R. prowazekii strains Breinl, RP22, and Madrid E. We found that in vitro trimethylation occurs at relatively specific locations in OmpB with consensus motifs, KX(G/A/V/I)N and KT(I/L/F), whereas monomethylation is pervasive throughout OmpB. Native OmpB from virulent R. typhi contains mono- and trimethyllysines at locations well correlated with methylation in recombinant OmpB catalyzed by methyltransferases in vitro. Native OmpBs from highly virulent R. prowazekii strains Breinl and RP22 contain multiple clusters of trimethyllysine in contrast to a single cluster in OmpB from mildly virulent R. typhi. Furthermore, OmpB from the avirulent strain Madrid E contains mostly monomethyllysine and no trimethyllysine. The native OmpB from Madrid E was minimally trimethylated by RT0101 or RP027-028, consistent with a processive mechanism of trimethylation. This study provides the first in-depth characterization of methylation of an OMP at the molecular level and may lead to uncovering the link between OmpB methylation and rickettsial virulence.
C1 [Abeykoon, Amila; Yang, David C. H.] Georgetown Univ, Dept Chem, Washington, DC 20057 USA.
[Wang, Guanghui; Gucek, Marjan] NHLBI, Prote Core Facil, NIH, Bethesda, MD 20892 USA.
[Chao, Chien-Chung; Ching, Wei-Mei] Naval Med Res Ctr, Viral & Rickettsial Dis Dept, Infect Dis Directorate, Silver Spring, MD 20910 USA.
[Chock, P. Boon] NHLBI, Biochem Lab, Bethesda, MD 20892 USA.
RP Yang, DCH (reprint author), Georgetown Univ, Dept Chem, Washington, DC 20057 USA.
EM yangdc@georgetown.edu
RI Yang, David/A-7294-2009
FU Naval Medical Logistic Command Award [N62645]; [6000.RAD1.J.A0310]
FX The work was supported by Naval Medical Logistic Command Award N62645
(to Georgetown University) and Work Unit 6000.RAD1.J.A0310 (to the Naval
Medical Research Center).
NR 44
TC 8
Z9 8
U1 1
U2 9
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAR 14
PY 2014
VL 289
IS 11
BP 7691
EP 7701
DI 10.1074/jbc.M113.535567
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AC8CV
UT WOS:000332761500037
PM 24497633
ER
PT J
AU Koorella, C
Nair, JR
Murray, ME
Carlson, LM
Watkins, SK
Lee, KP
AF Koorella, Chandana
Nair, Jayakumar R.
Murray, Megan E.
Carlson, Louise M.
Watkins, Stephanie K.
Lee, Kelvin P.
TI Novel Regulation of CD80/CD86-induced Phosphatidylinositol 3-Kinase
Signaling by NOTCH1 Protein in Interleukin-6 and Indoleamine
2,3-Dioxygenase Production by Dendritic Cells
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Dendritic Cells; Interleukin; NOTCH Pathway; PI 3-Kinase (PI3K); Signal
Transduction; Indoleamine 2; 3-Dioxygenase
ID NITRIC-OXIDE SYNTHASE; CD4(+) T-CELLS; MALIGNANT PLASMA-CELLS;
TRANSCRIPTION FACTOR; TRYPTOPHAN CATABOLISM; DEPENDENT PATHWAY; STROMAL
CELLS; CD28 FUNCTION; IN-VITRO; PTEN
AB Background: Engagement of CD80/CD86 on dendritic cells by CD28 on T cells induces dendritic cell production of IL-6 and IDO. Results: The NOTCH pathway modulates activation of the PI3K pathway downstream of CD80/CD86 ligation and regulates IL-6 and IDO production. Conclusion: Cross-talk between NOTCH and PI3K pathways modulates dendritic cell production of IL-6 and IDO. Significance: Elucidating the molecular mechanism of NOTCH-PI3K cross-talk will have broad implications in human disease.
Dendritic cells (DC) play a critical role in modulating antigen-specific immune responses elicited by T cells via engagement of the prototypic T cell costimulatory receptor CD28 by the cognate ligands CD80/CD86, expressed on DC. Although CD28 signaling in T cell activation has been well characterized, it has only recently been shown that CD80/CD86, which have no demonstrated binding domains for signaling proteins in their cytoplasmic tails, nonetheless also transduce signals to the DC. Functionally, CD80/CD86 engagement results in DC production of the pro-inflammatory cytokine IL-6, which is necessary for full T cell activation. However, ligation of CD80/CD86 by CTLA4 also induces DC production of the immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO), which depletes local pools of the essential amino acid tryptophan, resulting in blockade of T cell activation. Despite the significant role of CD80/CD86 in immunological processes and the seemingly opposing roles they play by producing IL-6 and IDO upon their activation, how CD80/CD86 signal remains poorly understood. We have now found that cross-linking CD80/CD86 in human DC activates the PI3K/AKT pathway. This results in phosphorylation/inactivation of its downstream target, FOXO3A, and alleviates FOXO3A-mediated suppression of IL-6 expression. A second event downstream of AKT phosphorylation is activation of the canonical NF-B pathway, which induces IL-6 expression. In addition to these downstream pathways, we unexpectedly found that CD80/CD86-induced PI3K signaling is regulated by previously unrecognized cross-talk with NOTCH1 signaling. This cross-talk is facilitated by NOTCH-mediated up-regulation of the expression of prolyl isomerase PIN1, which in turn increases enzyme activity of casein kinase II. Subsequently, phosphatase and tensin homolog (which suppresses PI3K activity) is inactivated via phosphorylation by casein kinase II. This results in full activation of PI3K signaling upon cross-linking CD80/CD86. Similar to IL-6, we have found that CD80/CD86-induced IDO production by DC at late time points is also dependent upon the PI3K AKT NF-B pathway and requires cross-talk with NOTCH signaling. These data further suggest that the same signaling pathways downstream of DC CD80/CD86 cross-linking induce early IL-6 production to enhance T cell activation, followed by later IDO production to self-limit this activation. In addition to characterizing the pathways downstream of CD80/CD86 in IL-6 and IDO production, identification of a novel cross-talk between NOTCH1 and PI3K signaling may provide new insights in other biological processes where PI3K signaling plays a major role.
C1 [Koorella, Chandana; Nair, Jayakumar R.; Murray, Megan E.; Carlson, Louise M.; Lee, Kelvin P.] Roswell Pk Canc Inst, Dept Immunol, Buffalo, NY 14263 USA.
[Watkins, Stephanie K.] NCI, Natl Inst Hlth, Frederick, MD 21702 USA.
RP Lee, KP (reprint author), Roswell Pk Canc Inst, Dept Immunol, Buffalo, NY 14263 USA.
EM Kelvin.Lee@roswellpark.org
FU National Institutes of Health [R01 CA140622, R01 CA121044, R01 AI10015,
T32 CA085183]; Multiple Myeloma Research Foundation
FX This work was supported, in whole or in part, by National Institutes of
Health Grants R01 CA140622, R01 CA121044, R01 AI10015, and T32 CA085183.
This work was also supported by the Multiple Myeloma Research
Foundation.
NR 51
TC 17
Z9 19
U1 0
U2 8
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAR 14
PY 2014
VL 289
IS 11
BP 7747
EP 7762
DI 10.1074/jbc.M113.519686
PG 16
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AC8CV
UT WOS:000332761500042
PM 24415757
ER
PT J
AU Jurgensen, HJ
Johansson, K
Madsen, DH
Porse, A
Melander, MC
Sorensen, KR
Nielsen, C
Bugge, TH
Behrendt, N
Engelholm, LH
AF Juergensen, Henrik J.
Johansson, Kristina
Madsen, Daniel H.
Porse, Astrid
Melander, Maria C.
Sorensen, Kristine R.
Nielsen, Christoffer
Bugge, Thomas H.
Behrendt, Niels
Engelholm, Lars H.
TI Complex Determinants in Specific Members of the Mannose Receptor Family
Govern Collagen Endocytosis
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Collagen; Endocytosis; Extracellular Matrix; Protein Chimeras; Receptor
Structure-Function; Intracellular Collagen Degradation; Mannose
Receptor; Cancer Invasion; Mannose Receptor Family; uPARAP; Endo180
ID SECRETORY PHOSPHOLIPASES A(2); GELATIN-BINDING DOMAIN; UROKINASE
RECEPTOR; MATRIX METALLOPROTEINASE-2; ENDOTHELIAL-CELLS;
MEMBRANE-RECEPTOR; LECTIN RECEPTOR; DENDRITIC CELLS; IV COLLAGENASE;
IN-VIVO
AB Background: Mannose receptor family members are candidate mediators of intracellular collagen degradation. Results: Despite common candidate collagen-binding domains and endocytic capacity throughout the family, only uPARAP/Endo180 and MR internalize collagens. Conclusion: A multi-domain interplay in the active receptors governs collagen endocytosis. Significance: Identification of the principal collagen receptors allows elucidation of the biological importance of intracellular collagen degradation.
Members of the well-conserved mannose receptor (MR) protein family have been functionally implicated in diverse biological and pathological processes. Importantly, a proposed common function is the internalization of collagen for intracellular degradation occurring during bone development, cancer invasion, and fibrosis protection. This functional relationship is suggested by a common endocytic capability and a candidate collagen-binding domain. Here we conducted a comparative investigation of each member's ability to facilitate intracellular collagen degradation. As expected, the family members uPARAP/Endo180 and MR bound collagens in a purified system and internalized collagens for degradation in cellular settings. In contrast, the remaining family members, PLA(2)R and DEC-205, showed no collagen binding activity and were unable to mediate collagen internalization. To pinpoint the structural elements discriminating collagen from non-collagen receptors, we constructed a series of receptor chimeras and loss- and gain-of-function mutants. Using this approach we identified a critical collagen binding loop in the suggested collagen binding region (an FN-II domain) in uPARAP/Endo180 and MR, which was different in PLA(2)R or DEC-205. However, we also found that an active FN-II domain was not a sufficient determinant to allow collagen internalization through these receptors. Nevertheless, this ability could be acquired by the transfer of a larger segment of uPARAP/Endo180 (the Cys-rich domain, the FN-II domain and two CTLDs) to DEC-205. These data underscore the importance of the FN-II domain in uPARAP/Endo180 and MR-mediated collagen internalization but at the same time uncover a critical interplay with flanking domains.
C1 [Juergensen, Henrik J.; Johansson, Kristina; Madsen, Daniel H.; Porse, Astrid; Melander, Maria C.; Sorensen, Kristine R.; Nielsen, Christoffer; Behrendt, Niels; Engelholm, Lars H.] Rigshosp, Finsen Lab, Biotech Res & Innovat Ctr, DK-2200 Copenhagen, Denmark.
[Juergensen, Henrik J.; Madsen, Daniel H.; Bugge, Thomas H.] NIDCR, Proteases & Tissue Remodeling Sect, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA.
RP Engelholm, LH (reprint author), Rigshosp, Finsen Lab, Copenhagen Bioctr, BRIC, Ole Maaloesvej 5, DK-2200 Copenhagen N, Denmark.
EM lhe@finsenlab.dk
OI Madsen, Daniel Hargboel/0000-0002-3183-6201; Engelholm,
Lars/0000-0002-6616-1232
FU NIDCR Intramural Research Program; Danish Cancer Society; Danish Medical
Research Council; Danish Cancer Research Foundation; Novo Nordisk
Foundation; Danish National Research Foundation (Danish-Chinese Center
for Proteases and Cancer); European Community [201279]; Lundbeck
Foundation; "Grosserer Alfred Nielsen og Hustrus" foundation;
Rigshospitalet/Copenhagen University Hospital
FX This work was supported by the NIDCR Intramural Research Program (D. M.
and T. H. B.), the Danish Cancer Society, the Danish Medical Research
Council, the Danish Cancer Research Foundation, the Novo Nordisk
Foundation, the Danish National Research Foundation (Danish-Chinese
Center for Proteases and Cancer) and the European Community's Seventh
Framework Programme FP7/2007-2011 under Grant agreement no 201279 (to M.
C. M. and N. B.), by the Lundbeck Foundation (to D. H. M. and L. H. E.),
the "Grosserer Alfred Nielsen og Hustrus" foundation (to L. H. E.). The
work was also supported by personal grants from
Rigshospitalet/Copenhagen University Hospital (to H. J. J. and A. P.).
NR 67
TC 10
Z9 11
U1 0
U2 4
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAR 14
PY 2014
VL 289
IS 11
BP 7935
EP 7947
DI 10.1074/jbc.M113.512780
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AC8CV
UT WOS:000332761500058
PM 24500714
ER
PT J
AU Matyas, GR
Rice, KC
Cheng, K
Li, F
Antoline, JFG
Iyer, MR
Jacobson, AE
Mayorov, AV
Beck, Z
Torres, OB
Alving, CR
AF Matyas, Gary R.
Rice, Kenner C.
Cheng, Kejun
Li, Fuying
Antoline, Joshua F. G.
Iyer, Malliga R.
Jacobson, Arthur E.
Mayorov, Alexander V.
Beck, Zoltan
Torres, Oscar B.
Alving, Carl R.
TI Facial recognition of heroin vaccine opiates: Type 1 cross-reactivities
of antibodies induced by hydrolytically stable haptenic surrogates of
heroin, 6-acetylmorphine, and morphine
SO VACCINE
LA English
DT Article
DE Haptens; Heroin; 6-Acetylmorphine; Morphine; Type 1 and type 2
cross-reactivity; Liposomes; Monophosphoryl lipid A; Tetanus toxoid;
Vaccines to drugs of abuse
ID CONJUGATE VACCINE; ADJUVANT SYSTEM; RELAPSE; BEHAVIORS; LIPOSOMES;
ABUSE; RATS
AB Novel synthetic compounds similar to heroin and its major active metabolites, 6-acetylmorphine and morphine, were examined as potential surrogate haptens for the ability to interface with the immune system for a heroin vaccine. Recent studies have suggested that heroin-like haptens must degrade hydrolytically to induce independent immune responses both to heroin and to the metabolites, resulting in antisera containing mixtures of antibodies (type 2 cross-reactivity). To test this concept, two unique hydrolytically stable haptens were created based on presumed structural facial similarities to heroin or to its active metabolites. After conjugation of a heroin-like hapten (DiAmHap) to tetanus toxoid and mixing with liposomes containing monophosphotyl lipid A, high titers of antibodies after two injections in mice had complementary binding sites that exhibited strong type 1 ("true") specific cross-reactivity with heroin and with both of its physiologically active metabolites. Mice immunized with each surrogate hapten exhibited reduced antinociceptive effects caused by injection of heroin. This approach obviates the need to create hydrolytically unstable synthetic heroin-like compounds to induce independent immune responses to heroin and its active metabolites for vaccine development. Facial recognition of hydrolytically stable surrogate haptens by antibodies together with type 1 cross-reactivities with heroin and its metabolites can help to guide synthetic chemical strategies for efficient development of a heroin vaccine. (C) 2014 Published by Elsevier Ltd.
C1 [Matyas, Gary R.; Mayorov, Alexander V.; Beck, Zoltan; Torres, Oscar B.; Alving, Carl R.] Walter Reed Army Inst Res, US Mil HIV Res Program, Lab Adjuvant & Antigen Res, Silver Spring, MD 20910 USA.
[Rice, Kenner C.; Cheng, Kejun; Li, Fuying; Antoline, Joshua F. G.; Jacobson, Arthur E.] Natl Inst Drug Abuse, Drug Design & Synth Sect, Chem Biol Res Branch, Bethesda, MD 20892 USA.
[Rice, Kenner C.; Cheng, Kejun; Li, Fuying; Antoline, Joshua F. G.; Jacobson, Arthur E.] NIAAA, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Rice, Kenner C.; Cheng, Kejun; Li, Fuying; Antoline, Joshua F. G.; Iyer, Malliga R.; Jacobson, Arthur E.] NIAAA, NIH, Bethesda, MD 20892 USA.
[Mayorov, Alexander V.; Beck, Zoltan; Torres, Oscar B.] Henry M Jackson Fdn Adv Mil Med, US Mil HIV Res Program, Bethesda, MD 20817 USA.
RP Alving, CR (reprint author), Walter Reed Army Inst Res, US Mil HIV Res Program, Lab Adjuvant & Antigen Res, 503 Robert Grant Ave, Silver Spring, MD 20910 USA.
EM calving@hivresearch.org
OI Matyas, Gary/0000-0002-2074-2373
FU Henry M. Jackson Foundation for the Advancement of Military Medicine
[W81XWH-07-2-067]; U.S. Army Medical Research and Materiel Command
(MRMC); National Institute on Drug Abuse (NIH) [1DP1DA034787-01]; NIH
Intramural Research Programs of the National Institute on Drug Abuse;
National Institute of Alcohol Abuse and Alcoholism; NIH; DHHS
FX This work was supported through a Cooperative Agreement Award (no.
W81XWH-07-2-067) between the Henry M. Jackson Foundation for the
Advancement of Military Medicine and the U.S. Army Medical Research and
Materiel Command (MRMC). The work was partially supported by an Avant
Garde award to GRM from the National Institute on Drug Abuse (NIH grant
no. 1DP1DA034787-01). The work of KC, FL, MRI, AEJ, and KCR was
supported by the NIH Intramural Research Programs of the National
Institute on Drug Abuse and the National Institute of Alcohol Abuse and
Alcoholism, NIH, DHHS. The authors thank Dr. Jay A. Berzofsky (NCI, NIH)
for useful discussion of type 1 and type 2 cross-reactivity; Ms. Elaine
Morrison, Ms. Courtney Tucker and Mr. Marcus Gallon provided outstanding
technical assistance. Research was conducted in compliance with the
Animal Welfare Act and other federal statutes and regulations relating
to animals and experiments involving animals and adhered to principles
stated in the Guide for the Care and Use of Laboratory Animals, NRC
Publication, 1996 edition. The views expressed in this article are those
of the authors and do not necessarily reflect the official policy of the
Department of the Army, Department of Defense, or NIH, or the U.S.
Government.
NR 18
TC 7
Z9 7
U1 0
U2 3
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
EI 1873-2518
J9 VACCINE
JI Vaccine
PD MAR 14
PY 2014
VL 32
IS 13
BP 1473
EP 1479
DI 10.1016/j.vaccine.2014.01.028
PG 7
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA AG7SC
UT WOS:000335617600009
PM 24486371
ER
PT J
AU Knight, JS
Luo, W
O'Dell, AA
Yalavarthi, S
Zhao, WP
Subramanian, V
Guo, CA
Grenn, RC
Thompson, PR
Eitzman, DT
Kaplan, MJ
AF Knight, Jason S.
Luo, Wei
O'Dell, Alexander A.
Yalavarthi, Srilakshmi
Zhao, Wenpu
Subramanian, Venkataraman
Guo, Chiao
Grenn, Robert C.
Thompson, Paul R.
Eitzman, Daniel T.
Kaplan, Mariana J.
TI Peptidylarginine Deiminase Inhibition Reduces Vascular Damage and
Modulates Innate Immune Responses in Murine Models of Atherosclerosis
SO CIRCULATION RESEARCH
LA English
DT Article
DE atherosclerosis; immunology; interferon-; neutrophils; protein-arginine
deiminase; thrombosis
ID NEUTROPHIL EXTRACELLULAR TRAPS; E-DEFICIENT MICE; PLASMACYTOID DENDRITIC
CELLS; DEEP-VEIN THROMBOSIS; CARDIOVASCULAR-DISEASE; INTERFERON-ALPHA;
KNOCKOUT MICE; LUPUS; LESIONS; DNA
AB Rationale: Neutrophil extracellular trap (NET) formation promotes vascular damage, thrombosis, and activation of interferon--producing plasmacytoid dendritic cells in diseased arteries. Peptidylarginine deiminase inhibition is a strategy that can decrease in vivo NET formation.
Objective: To test whether peptidylarginine deiminase inhibition, a novel approach to targeting arterial disease, can reduce vascular damage and inhibit innate immune responses in murine models of atherosclerosis.
Methods and Results:Apolipoprotein-E (Apoe)(-/-) mice demonstrated enhanced NET formation, developed autoantibodies to NETs, and expressed high levels of interferon- in diseased arteries. Apoe(-/-) mice were treated for 11 weeks with daily injections of Cl-amidine, a peptidylarginine deiminase inhibitor. Peptidylarginine deiminase inhibition blocked NET formation, reduced atherosclerotic lesion area, and delayed time to carotid artery thrombosis in a photochemical injury model. Decreases in atherosclerosis burden were accompanied by reduced recruitment of netting neutrophils and macrophages to arteries, as well as by reduced arterial interferon- expression.
Conclusions: Pharmacological interventions that block NET formation can reduce atherosclerosis burden and arterial thrombosis in murine systems. These results support a role for aberrant NET formation in the pathogenesis of atherosclerosis through modulation of innate immune responses.
C1 [Knight, Jason S.; O'Dell, Alexander A.; Yalavarthi, Srilakshmi; Grenn, Robert C.] Univ Michigan, Sch Med, Dept Rheumatol, Ann Arbor, MI USA.
[Luo, Wei; Guo, Chiao; Eitzman, Daniel T.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA.
[Zhao, Wenpu; Kaplan, Mariana J.] NIAMSD, Syst Autoimmun Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Subramanian, Venkataraman; Thompson, Paul R.] Scripps Res Inst, Dept Chem, Jupiter, FL USA.
RP Knight, JS (reprint author), Univ Michigan, Dept Internal Med, Div Rheumatol, 5520 MSRB 1,1150 W Med Ctr Dr,SPC 5680, Ann Arbor, MI 48109 USA.
EM jsknight@umich.edu; mariana.kaplan@nih.gov
FU National Institutes of Health (NIH) through Public Health Service grant
[HL088419]; Rheumatology Research Foundation Rheumatology Scientist
Development Award; NIH [GM079357, CA151304]
FX This work was supported by the National Institutes of Health (NIH)
through Public Health Service grant HL088419 (to M.J. Kaplan). J.S.
Knight was supported by a Rheumatology Research Foundation Rheumatology
Scientist Development Award. P.R. Thompson is supported by NIH grants
GM079357 and CA151304. This article was prepared while W. Zhao and M.J.
Kaplan were employed at the University of Michigan. The opinions
expressed in this article are the authors' own and do not reflect the
view of the National Institutes of Health, the Department of Health and
Human Services, or the US government.
NR 48
TC 53
Z9 53
U1 1
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7330
EI 1524-4571
J9 CIRC RES
JI Circ.Res.
PD MAR 14
PY 2014
VL 114
IS 6
BP 947
EP 956
DI 10.1161/CIRCRESAHA.114.303312
PG 10
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA AE0IF
UT WOS:000333646900010
PM 24425713
ER
PT J
AU Killeen, GF
Chitnis, N
AF Killeen, Gerry F.
Chitnis, Nakul
TI Potential causes and consequences of behavioural resilience and
resistance in malaria vector populations: a mathematical modelling
analysis
SO MALARIA JOURNAL
LA English
DT Article
DE Plasmodium; Anopheles; Malaria; Behaviour; Resistance; Vector control;
Endophagic; Exophagic; Endophilic; Exophilic
ID INSECTICIDE-TREATED NETS; ANOPHELES-ARABIENSIS; BED NETS;
ENTOMOPATHOGENIC FUNGI; PLASMODIUM-FALCIPARUM; TRANSMISSION DYNAMICS;
HUMAN EXPOSURE; AEDES-AEGYPTI; MOSQUITO; TANZANIA
AB Background: The ability of mosquitoes to evade fatal exposure to insecticidal nets and sprays represents the primary obstacle to eliminating malaria. However, it remains unclear which behaviours are most important for buffering mosquito and parasite populations against vector control.
Methods: Simulated life histories were used to compare the impact of alternative feeding behaviour strategies upon overall lifetime feeding success, and upon temporal distributions of successful feeds and biting rates experienced by unprotected humans, in the presence and absence of insecticidal nets. Strictly nocturnal preferred feeding times were contrasted with 1) a wider preference window extending to dawn and dusk, and 2) crepuscular preferences wherein foraging is suppressed when humans sleep and can use nets but is maximal immediately before and after. Simulations with diversion and mortality parameters typical of endophagic, endophilic African vectors, such as Anopheles gambiae and Anopheles funestus, were compared with those for endophagic but exophilic species, such as Anopheles arabiensis, that also enter houses but leave earlier before lethal exposure to insecticide-treated surfaces occurs.
Results: Insecticidal nets were predicted to redistribute successful feeding events to dawn and dusk where these were included in the profile of innately preferred feeding times. However, predicted distributions of biting unprotected humans were unaffected because extended host-seeking activity was redistributed to innately preferred feeding times. Recently observed alterations of biting activity distributions therefore reflect processes not captured in this model, such as evolutionary selection of heritably modified feeding time preferences or phenotypically plastic expression of feeding time preference caused by associative learning. Surprisingly, endophagy combined with exophily, among mosquitoes that enter houses but then feed and/or rest briefly before rapidly exiting, consistently attenuated predicted insecticide impact more than any feeding time preference trait.
Conclusions: Regardless of underlying cause, recent redistributions of host-biting activity to dawn and dusk necessitate new outdoor control strategies. However, persistently indoor-feeding vectors, that evade intradomiciliary insecticide exposure, are at least equally important. Fortunately, recent evaluations of occupied houses or odour-baited stations, with baffled entrances that retain An. arabiensis within insecticide-treated structures, illustrate how endophagic but exophilic vectors may be more effectively tackled using existing insecticides.
C1 [Killeen, Gerry F.] Ifakara Hlth Inst, Environm Hlth & Ecol Sci Themat Grp, Morogoro, Tanzania.
[Killeen, Gerry F.] Univ Liverpool, Liverpool Sch Trop Med, Dept Vector Biol, Liverpool L3 5QA, Merseyside, England.
[Chitnis, Nakul] Swiss Trop & Publ Hlth Inst, Dept Epidemiol & Publ Hlth, CH-4002 Basel, Switzerland.
[Chitnis, Nakul] Univ Basel, Basel, Switzerland.
[Chitnis, Nakul] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Killeen, GF (reprint author), Ifakara Hlth Inst, Environm Hlth & Ecol Sci Themat Grp, POB 53, Morogoro, Tanzania.
EM gkilleen@ihi.or.tz
RI Chitnis, Nakul/B-3105-2013
FU Bill & Melinda Gates Foundation [45114, 52644, OPP1032350]; European
Union [265660]
FX We thank O J Briet, F O Okumu and N J Govella for comments on the
manuscript, as well as F C Collins and T L Russell for discussions that
stimulated this analysis. The research leading to this manuscript has
received funding from the Bill & Melinda Gates Foundation (award numbers
45114, 52644 and OPP1032350) and the European Union Seventh Framework
Programme FP7/2007-2013 (grant agreement 265660).
NR 66
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Z9 16
U1 5
U2 22
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 MAR 14
PY 2014
VL 13
AR 97
DI 10.1186/1475-2875-13-97
PG 16
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA AF6CS
UT WOS:000334802600003
PM 24629066
ER
PT J
AU Hasin, N
Cusack, SA
Ali, SS
Fitzpatrick, DA
Jones, GW
AF Hasin, Naushaba
Cusack, Sarah A.
Ali, Shahin S.
Fitzpatrick, David A.
Jones, Gary W.
TI Global transcript and phenotypic analysis of yeast cells expressing
Ssa1, Ssa2, Ssa3 or Ssa4 as sole source of cytosolic Hsp70-Ssa chaperone
activity
SO BMC GENOMICS
LA English
DT Article
DE Saccharomyces cerevisiae; Prion; Heat shock; Stress; Hsp70; Ssa1; Ssa2;
Ssa3; Ssa4; Chaperone; Gene expression
ID NUCLEOTIDE EXCHANGE FACTOR; HEAT-SHOCK PROTEINS;
SACCHAROMYCES-CEREVISIAE; PRION PROPAGATION; MOLECULAR CHAPERONES;
IN-VIVO; GUANIDINE-HYDROCHLORIDE; FUNCTIONAL SPECIFICITY; MAMMALIAN
PRIONS; OXIDATIVE STRESS
AB Background: Cytosolic Hsp70 is a ubiquitous molecular chaperone that is involved in responding to a variety of cellular stresses. A major function of Hsp70 is to prevent the aggregation of denatured proteins by binding to exposed hydrophobic regions and preventing the accumulation of amorphous aggregates. To gain further insight into the functional redundancy and specialisation of the highly homologous yeast Hsp70-Ssa family we expressed each of the individual Ssa proteins as the sole source of Hsp70 in the cell and assessed phenotypic differences in prion propagation and stress resistance. Additionally we also analysed the global gene expression patterns in yeast strains expressing individual Ssa proteins, using microarray and RT-qPCR analysis.
Results: We confirm and extend previous studies demonstrating that cells expressing different Hsp70-Ssa isoforms vary in their ability to propagate the yeast [PSI+] prion, with Ssa3 being the most proficient. Of the four Ssa family members the heat inducible isoforms are more proficient in acquiring thermotolerance and we show a greater requirement than was previously thought, for cellular processes in addition to the traditional Hsp104 protein disaggregase machinery, in acquiring such thermotolerance. Cells expressing different Hsp70-Ssa isoforms also display differences in phenotypic response to exposure to cell wall damaging and oxidative stress agents, again with the heat inducible isoforms providing better protection than constitutive isoforms. We assessed global transcriptome profiles for cells expressing individual Hsp70-Ssa isoforms as the sole source of cytosolic Hsp70, and identified a significant difference in cellular gene expression between these strains. Differences in gene expression profiles provide a rationale for some phenotypic differences we observed in this study. We also demonstrate a high degree of correlation between microarray data and RT-qPCR analysis for a selection of genes.
Conclusions: The Hsp70-Ssa family provide both redundant and variant-specific functions within the yeast cell. Yeast cells expressing individual members of the Hsp70-Ssa family as the sole source of Ssa protein display differences in global gene expression profiles. These changes in global gene expression may contribute significantly to the phenotypic differences observed between the Hsp70-Ssa family members.
C1 [Hasin, Naushaba; Cusack, Sarah A.; Jones, Gary W.] Natl Univ Ireland Maynooth, Dept Biol, Yeast Genet Lab, Maynooth, Kildare, Ireland.
[Hasin, Naushaba] NICHHD, Sect Format RNA, NIH, Bethesda, MD 20814 USA.
[Ali, Shahin S.] ARS, Sustainable Perennial Crops Lab, USDA, Beltsville, MD USA.
[Fitzpatrick, David A.] Natl Univ Ireland Maynooth, Dept Biol, Genome Evolut Lab, Maynooth, Kildare, Ireland.
RP Jones, GW (reprint author), Natl Univ Ireland Maynooth, Dept Biol, Yeast Genet Lab, Maynooth, Kildare, Ireland.
EM gary.jones@nuim.ie
OI Fitzpatrick, David/0000-0001-7345-6998
FU Science Foundation Ireland [RFP/07/BIC493]; John and Pat Hume
postgraduate scholarship; Toray Industries as part of a 3D-Gene(TM)
Competition Award
FX We thank Daniel Masison for plasmids, Elizabeth Craig and John Glover
for antibodies, used in this study. This work was supported in part by
Science Foundation Ireland grant RFP/07/BIC493 awarded to GWJ. NH was
supported by a John and Pat Hume postgraduate scholarship. Microarray
analysis was performed by Toray Industries as part of a 3D-Gene (TM)
Competition Award to GWJ.
NR 70
TC 10
Z9 11
U1 5
U2 17
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 MAR 14
PY 2014
VL 15
AR 194
DI 10.1186/1471-2164-15-194
PG 12
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA AD8QB
UT WOS:000333529600003
PM 24628813
ER
PT J
AU Sen, SK
Barb, JJ
Cherukuri, PF
Accame, DS
Elkahloun, AG
Singh, LN
Lee-Lin, SQ
Kolodgie, FD
Cheng, Q
Zhao, XQ
Chen, MY
Arai, AE
Green, ED
Mullikin, JC
Munson, PJ
Biesecker, LG
AF Sen, Shurjo K.
Barb, Jennifer J.
Cherukuri, Praveen F.
Accame, David S.
Elkahloun, Abdel G.
Singh, Larry N.
Lee-Lin, Shih-Queen
Kolodgie, Frank D.
Cheng, Qi
Zhao, XiaoQing
Chen, Marcus Y.
Arai, Andrew E.
Green, Eric D.
Mullikin, James C.
Munson, Peter J.
Biesecker, Leslie G.
CA NISC Comparative Sequencing
TI Identification of candidate genes involved in coronary artery
calcification by transcriptome sequencing of cell lines
SO BMC GENOMICS
LA English
DT Article
DE Coronary artery calcification; RNA-Seq; Lymphoblastoid cell lines;
Transcriptome profiling
ID GENOME-WIDE ASSOCIATION; 2010 ACCF/AHA GUIDELINE; INTIMA-MEDIA
THICKNESS; RNA-SEQ; DIFFERENTIAL EXPRESSION; ATHEROSCLEROSIS MESA;
ASYMPTOMATIC ADULTS; CARDIOVASCULAR RISK; TASK-FORCE; DISEASE
AB Background: Massively-parallel cDNA sequencing (RNA-Seq) is a new technique that holds great promise for cardiovascular genomics. Here, we used RNA-Seq to study the transcriptomes of matched coronary artery disease cases and controls in the ClinSeq (R) study, using cell lines as tissue surrogates.
Results: Lymphoblastoid cell lines (LCLs) from 16 cases and controls representing phenotypic extremes for coronary calcification were cultured and analyzed using RNA-Seq. All cell lines were then independently re-cultured and along with another set of 16 independent cases and controls, were profiled with Affymetrix microarrays to perform a technical validation of the RNA-Seq results. Statistically significant changes (p < 0.05) were detected in 186 transcripts, many of which are expressed at extremely low levels (5-10 copies/cell), which we confirmed through a separate spike-in control RNA-Seq experiment. Next, by fitting a linear model to exon-level RNA-Seq read counts, we detected signals of alternative splicing in 18 transcripts. Finally, we used the RNA-Seq data to identify differential expression (p < 0.0001) in eight previously unannotated regions that may represent novel transcripts. Overall, differentially expressed genes showed strong enrichment (p = 0.0002) for prior association with cardiovascular disease. At the network level, we found evidence for perturbation in pathways involving both cardiovascular system development and function as well as lipid metabolism.
Conclusions: We present a pilot study for transcriptome involvement in coronary artery calcification and demonstrate how RNA-Seq analyses using LCLs as a tissue surrogate may yield fruitful results in a clinical sequencing project. In addition to canonical gene expression, we present candidate variants from alternative splicing and novel transcript detection, which have been unexplored in the context of this disease.
C1 [Sen, Shurjo K.; Cherukuri, Praveen F.; Accame, David S.; Elkahloun, Abdel G.; Singh, Larry N.; Lee-Lin, Shih-Queen; Green, Eric D.; Mullikin, James C.; Biesecker, Leslie G.; NISC Comparative Sequencing] NHGRI, NIH, Bethesda, MD 20892 USA.
[Barb, Jennifer J.; Munson, Peter J.] NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA.
[Kolodgie, Frank D.; Cheng, Qi; Zhao, XiaoQing] CVPath Inst Inc, Gaithersburg, MD 20878 USA.
[Chen, Marcus Y.; Arai, Andrew E.] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Biesecker, LG (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA.
EM lesb@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health
FX The authors thank Peter Chines, Nancy Hansen, Jamie Teer, and Aaron
Quinlan for computational analyses, Robert Blakesley, Alice Young,
Michael Erdos, Marjorie Lindhurst, Jacquelyn Idol, and Jennifer Johnston
for help with experimental procedures, Julia Fekecs for help with
preparing high-resolution graphics, Soma Chowdhury for proofreading, and
Flavia Facio, David Ng, Clesson Turner, and the ClinSeq (R) clinical
support and nursing staff for their help with the clinical aspects of
this study. We thank Eric Olivares and the SEQanswers community
(http://SEQanswers.com) for providing valuable advice. Above all, we are
grateful to the many participants of the ClinSeq (R) study. This study
is supported by funds from the Intramural Research Program of the
National Institutes of Health.
NR 32
TC 1
Z9 1
U1 1
U2 12
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 MAR 14
PY 2014
VL 15
AR 198
DI 10.1186/1471-2164-15-198
PG 12
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA AD8QB
UT WOS:000333529600007
PM 24628908
ER
PT J
AU Lucifora, J
Xia, YC
Reisinger, F
Zhang, K
Stadler, D
Cheng, XM
Sprinzl, MF
Koppensteiner, H
Makowska, Z
Volz, T
Remouchamps, C
Chou, WM
Thasler, WE
Huser, N
Durantel, D
Liang, TJ
Munk, C
Heim, MH
Browning, JL
Dejardin, E
Dandri, M
Schindler, M
Heikenwalder, M
Protzer, U
AF Lucifora, Julie
Xia, Yuchen
Reisinger, Florian
Zhang, Ke
Stadler, Daniela
Cheng, Xiaoming
Sprinzl, Martin F.
Koppensteiner, Herwig
Makowska, Zuzanna
Volz, Tassilo
Remouchamps, Caroline
Chou, Wen-Min
Thasler, Wolfgang E.
Hueser, Norbert
Durantel, David
Liang, T. Jake
Muenk, Carsten
Heim, Markus H.
Browning, Jeffrey L.
Dejardin, Emmanuel
Dandri, Maura
Schindler, Michael
Heikenwalder, Mathias
Protzer, Ulrike
TI Specific and Nonhepatotoxic Degradation of Nuclear Hepatitis B Virus
cccDNA
SO SCIENCE
LA English
DT Article
ID LYMPHOTOXIN-BETA-RECEPTOR; GENE-EXPRESSION; HEPATOCELLULAR-CARCINOMA;
CYTIDINE DEAMINASES; HUMAN HEPATOCYTES; TRANSGENIC MICE; HBV INFECTION;
FOREIGN DNA; IN-VITRO; REPLICATION
AB Current antiviral agents can control but not eliminate hepatitis B virus (HBV), because HBV establishes a stable nuclear covatently closed circular DNA (cccDNA), Interferon-alpha treatment can clear HBV but is limited by systemic side effects. We describe how interferon-alpha can induce specific degradation of the nuclear viral DNA without hepatotoxicity and propose lymphotoxin-beta receptor activation as a therapeutic alternative. Interferon-alpha and lymphotoxin-beta receptor activation up-regulated APOBEC3A and APOBEC3B cytidine deaminases, respectively, in HBV-infected cells, primary hepatocytes, and human liver needle biopsies. HBV core protein mediated the interaction with nuclear cccDNA, resulting in cytidine deamination, apurinic/apyrimidinic site formation, and finally cccDNA degradation that prevented HBV reactivation. Genomic DNA was not affected. Thus, inducing nuclear deaminases-for example, by lymphotoxin-beta receptor activation-allows the development of new therapeutics that, in combination with existing antivirals, may cure hepatitis B.
C1 [Lucifora, Julie; Xia, Yuchen; Reisinger, Florian; Zhang, Ke; Stadler, Daniela; Cheng, Xiaoming; Sprinzl, Martin F.; Koppensteiner, Herwig; Chou, Wen-Min; Schindler, Michael; Heikenwalder, Mathias; Protzer, Ulrike] Tech Univ Munich, Helmholtz Zentrum Munchen, Inst Virol, D-81675 Munich, Germany.
[Lucifora, Julie; Dandri, Maura; Protzer, Ulrike] German Ctr Infect Res DZIF, Munich, Germany.
[Lucifora, Julie; Dandri, Maura; Protzer, Ulrike] German Ctr Infect Res DZIF, Hamburg Sites, Germany.
[Sprinzl, Martin F.] Univ Hosp Mainz, Dept Med 1, D-55131 Mainz, Germany.
[Makowska, Zuzanna; Heim, Markus H.] Univ Basel Hosp, Dept Biomed, CH-4031 Basel, Switzerland.
[Volz, Tassilo; Dandri, Maura] Univ Med Ctr Hamburg Eppendorf, Dept Internal Med, D-20246 Hamburg, Germany.
[Remouchamps, Caroline; Dejardin, Emmanuel] Univ Liege, GIGA Res Lab Mol Immunol & Signal Transduct, B-4000 Liege, Belgium.
[Thasler, Wolfgang E.] Univ Munich, Grosshadern Hosp, Dept Gen Visceral Transplantat Vasc & Thorac Surg, D-81377 Munich, Germany.
[Hueser, Norbert] Tech Univ Munich, Univ Hosp Rechts Isar, Dept Surg, D-85748 Munich, Germany.
[Durantel, David] Univ Lyon, LabEx DEVweCAN, Canc Res Ctr Lyon, INSERM,U1052,CNRS,UMR 5286, F-69007 Lyon, France.
[Liang, T. Jake] NIDDK, Liver Dis Branch, Bethesda, MD 20892 USA.
[Muenk, Carsten] Univ Dusseldorf, Fac Med, Clin Gastroenterol Hepatol & Infectiol, D-40225 Dusseldorf, Germany.
[Browning, Jeffrey L.] Biogen Idec Inc, Dept Immunobiol, Cambridge, MA 02142 USA.
RP Heikenwalder, M (reprint author), Tech Univ Munich, Helmholtz Zentrum Munchen, Inst Virol, D-81675 Munich, Germany.
EM heikenwaelder@helmholtz-muenchen.de; protzer@tum.de
RI Schindler, Michael/C-1647-2015;
OI Schindler, Michael/0000-0001-8989-5813; Xia, Yuchen/0000-0001-8460-3893;
Heim, Markus/0000-0002-7523-4894
FU Federation Beige Contre Le Cancer; European Research Council; German
Research Foundation [SFB 841, SFB TR 36, SFB TR 22]; Peter-Hans
Hofschneider Foundation; Helmholtz Alliances HAIT; PCCC; HTCR
FX We thank R. Rester, T. Asen, K. Ackermann, K. Kappes, M. Feuerherd, R.
Barer, R. Hillermann, U. Finkel, A. Krikoni, and F. Zhang for technical
support; L. Terracciano for analysis of acute hepatitis patients; F.
Chisari for HBV transgenic mice (HBV 1.3.32); T. Buch arid O. Prazeres
da Costa for help with array analysis and data discussions; L. Allweiss
and A. Groth for help in generating and treating humanized uPA-SCID
mice; and Siemens Healthcare Diagnostics for reagents. Supported by
grants from Federation Beige Contre Le Cancer (E.D.), a European
Research Council starting grant (LiverCancerMechanism) (M.H.), the
German Research Foundation (SFB 841 to M.D. SFB TR 36 to M.H. and SFB TR
22), the Peter-Hans Hofschneider Foundation and the Helmholtz Alliances
HAIT (U.P.), and PCCC (M.H.). We acknowledge the support of the
nonprofit foundation HTCR, winch holds human tissue on trust, making it
broadly available for research on an ethical and legal basis. Patent
application EP12006XXX has been filed at the European patent office:
"Lymphotoxin signaling activation and its downstream mediators eliminate
HBV ccc DNA." Microarray data have been submitted to the GEO database
(www.ncbi.nlm.nih.gov/geo/) with accession number GSE46667. Human liver
chimeric uPA-SCID mice were handled in accordance with protocols
approved by the ethical committee of the city and state of Hamburg
(permission number G12/015). Experiments with HBV-transgenic mice were
performed in accordance with German legislation governing animal studies
and the Principles of Laboratory Animal Care guidelines, NIH
(55.1-1-54-2531.3-27-08). The study protocol for the animal experiment
in fig. S128 was approved at the Southwest Foundation for Biomedical
Research, San Antonio, TX (IACUC 869 PT, approved in 2004).
NR 41
TC 204
Z9 219
U1 8
U2 66
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 MAR 14
PY 2014
VL 343
IS 6176
BP 1221
EP 1228
DI 10.1126/science.1243462
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC7RG
UT WOS:000332728500030
PM 24557838
ER
PT J
AU Bitar, C
Saba, N
AF Bitar, Carole
Saba, Nakhle
TI Neutrophil numerals
SO BLOOD
LA English
DT Editorial Material
C1 [Bitar, Carole] Univ Balamand, Koura, Lebanon.
[Saba, Nakhle] NIH, Bethesda, MD USA.
RP Bitar, C (reprint author), Univ Balamand, Koura, Lebanon.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD MAR 13
PY 2014
VL 123
IS 11
BP 1635
EP 1635
DI 10.1182/blood-2013-12-541797
PG 1
WC Hematology
SC Hematology
GA AH0YW
UT WOS:000335847700009
PM 24761452
ER
PT J
AU Bouska, A
McKeithan, TW
Deffenbacher, KE
Lachel, C
Wright, GW
Iqbal, J
Smith, LM
Zhang, WW
Kucuk, C
Rinaldi, A
Bertoni, F
Fitzgibbon, J
Fu, K
Weisenburger, DD
Greiner, TC
Dave, BJ
Gascoyne, RD
Rosenwald, A
Ott, G
Campo, E
Rimsza, LM
Delabie, J
Jaffe, ES
Braziel, RM
Connors, JM
Staudt, LM
Chan, WC
AF Bouska, Alyssa
McKeithan, Timothy W.
Deffenbacher, Karen E.
Lachel, Cynthia
Wright, George W.
Iqbal, Javeed
Smith, Lynette M.
Zhang, Weiwei
Kucuk, Can
Rinaldi, Andrea
Bertoni, Francesco
Fitzgibbon, Jude
Fu, Kai
Weisenburger, Dennis D.
Greiner, Timothy C.
Dave, Bhavana J.
Gascoyne, Randy D.
Rosenwald, Andreas
Ott, German
Campo, Elias
Rimsza, Lisa M.
Delabie, Jan
Jaffe, Elaine S.
Braziel, Rita M.
Connors, Joseph M.
Staudt, Louis M.
Chan, Wing-Chung
TI Genome-wide copy-number analyses reveal genomic abnormalities involved
in transformation of follicular lymphoma
SO BLOOD
LA English
DT Article
ID B-CELL LYMPHOMA; CHRONIC LYMPHOCYTIC-LEUKEMIA; NF-KAPPA-B; GERMINAL
CENTER; UNIPARENTAL DISOMY; CLONAL EVOLUTION; BINDING PROTEIN;
GENE-EXPRESSION; BREAST-CANCER; REPRESSION
AB Follicular lymphoma (FL), the second most common type of non-Hodgkin lymphoma in the western world, is characterized by the t(14; 18) translocation, which is present in up to 90% of cases. We studied 277 lymphoma samples (198 FL and 79 transformed FL [tFL]) using a single-nucleotide polymorphism array to identify the secondary chromosomal abnormalities that drive the development of FL and its transformation to diffuse large B-cell lymphoma. Common recurrent chromosomal abnormalities in FL included gains of 2, 5, 7, 6p, 8, 12, 17q, 18, 21, and X and losses on 6q and 17p. We also observed many frequent small abnormalities, including losses of 1p36.33-p36.31, 6q23.3-q24.1, and 10q23.1-q25.1 and gains of 2p16.1-p15, 8q24.13-q24.3, and 12q12-q13.13, and identified candidate genes that may be driving this selection. Recurrent abnormalities more frequent in tFL samples included gains of 3q27.3-q28 and chromosome 11 and losses of 9p21.3 and 15q. Four abnormalities, gain of X or Xp and losses of 6q23.2-24.1 or 6q13-15, predicted overall survival. Abnormalities associated with transformation of the disease likely impair immune surveillance, activate the nuclear factor-kappa B pathway, and deregulate p53 and B-cell transcription factors.
C1 [Bouska, Alyssa; McKeithan, Timothy W.; Deffenbacher, Karen E.; Lachel, Cynthia; Iqbal, Javeed; Zhang, Weiwei; Kucuk, Can; Fu, Kai; Greiner, Timothy C.; Chan, Wing-Chung] Univ Nebraska Med Ctr, Omaha, NE USA.
[Wright, George W.] NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[Smith, Lynette M.] Univ Nebraska Med Ctr, Coll Publ Hlth Biostat, Omaha, NE USA.
[Rinaldi, Andrea; Bertoni, Francesco] Oncol Res Inst, Lymphoma & Genom Res Program, Bellinzona, Switzerland.
[Bertoni, Francesco] Oncol Inst Southern Switzerland, Lymphoma Unit, Bellinzona, Switzerland.
[Fitzgibbon, Jude] Queen Mary Univ London, Barts Canc Inst, Ctr Haematooncol, London, England.
[Weisenburger, Dennis D.] City Hope Natl Med Ctr, Dept Pathol, Duarte, CA 91010 USA.
[Dave, Bhavana J.] Univ Nebraska Med Ctr, Ctr Human Genet, Omaha, NE USA.
[Gascoyne, Randy D.] British Columbia Canc Agcy, Ctr Lymphoid Canc, Vancouver, BC V5Z 4E6, Canada.
[Rosenwald, Andreas] Univ Wurzburg, D-97070 Wurzburg, Germany.
[Ott, German] Robert Bosch Krankenhaus, Dept Clin Pathol, Stuttgart, Germany.
[Ott, German] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany.
[Campo, Elias] Hosp Clin Barcelona, Hematopathol Unit, Barcelona, Spain.
[Rimsza, Lisa M.] Univ Arizona, Dept Pathol, Tucson, AZ USA.
[Delabie, Jan] Univ Toronto, Dept Pathol, Toronto, ON, Canada.
[Jaffe, Elaine S.] NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Braziel, Rita M.] Oregon Hlth & Sci Univ, Portland, OR USA.
[Connors, Joseph M.] British Columbia Canc Agcy, Div Med Oncol, Vancouver, BC V5Z 4E6, Canada.
[Staudt, Louis M.] NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Chan, WC (reprint author), Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Ctr Res Lymphoma & Leukemia, 983135 Nebraska Med Ctr, Omaha, NE 68198 USA.
EM jchan@unmc.edu
RI Kucuk, Can/K-3913-2015; Campo, elias/O-7192-2016;
OI Delabie, Jan/0000-0001-5023-0689; Jaffe, Elaine/0000-0003-4632-0301;
Bertoni, Francesco/0000-0001-5637-8983; Kucuk, Can/0000-0001-5540-9012;
Campo, elias/0000-0001-9850-9793; McKeithan, Timothy/0000-0003-2242-3074
FU Lymphoma Research Foundation Follicular Lymphoma Initiative; National
Institutes of Health Lymphoma SPORE [P50CA136411-01-(NC1)]; Oncosuisse
grant [OCS-1939-8-2006]; Nelia et Amadeo Barletta Foundation (Lausanne,
Switzerland)
FX This work was supported by the Lymphoma Research Foundation Follicular
Lymphoma Initiative (W.-C. C.), National Institutes of Health Lymphoma
SPORE P50CA136411-01-(NC1) (W.-C.C.), Oncosuisse grant OCS-1939-8-2006
(F.B.), and the Nelia et Amadeo Barletta Foundation (Lausanne,
Switzerland) (F.B.).
NR 56
TC 20
Z9 20
U1 1
U2 6
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD MAR 13
PY 2014
VL 123
IS 11
BP 1681
EP 1690
DI 10.1182/blood-2013-05-500595
PG 10
WC Hematology
SC Hematology
GA AH0YW
UT WOS:000335847700015
PM 24037725
ER
PT J
AU Yu, GQ
Fadrosh, D
Ma, B
Ravel, J
Goedert, JJ
AF Yu, Guoqin
Fadrosh, Doug
Ma, Bing
Ravel, Jacques
Goedert, James J.
TI Anal microbiota profiles in HIV-positive and HIV-negative MSM
SO AIDS
LA English
DT Article
DE anal; sexual activities; risk factors; HIV; MSM; human microbiome
ID BURROWS-WHEELER TRANSFORM; HOMOSEXUAL-MEN; BACTERIAL VAGINOSIS;
HUMAN-IMMUNODEFICIENCY; READ ALIGNMENT; GUT MICROBIOME; DIVERSITY;
WOMEN; AIDS
AB Objective: Because differences in anal microbial populations (microbiota) could affect acquisition of HIV or other conditions, especially among MSM, we profiled the microbiota of the anal canal, assessed its stability, and investigated associations with diversity and composition. Design: Microbiota profiles in anal swabs collected from 76 MSM (52 in 1989, swab-1; 66 1-5 years later, swab-2) were compared by HIV status (25 HIV-positive), T-cell subsets, and questionnaire data. Methods: Bacterial 16S rRNA genes were amplified, sequenced (Illumina MiSeq), and clustered into species-level operational taxonomic units (QIIME and Greengenes). Regression models and Wilcoxon tests were used for associations with alpha diversity (unique operational taxonomic units, Shannon's index). Composition was compared by Adonis (QIIME). Results: Most anal bacteria were Firmicutes (mean 60.6%, range 21.1-91.1%) or Bacteroidetes (29.4%, 4.1-70.8%). Alpha diversity did not change between the two swabs (N = 42 pairs). In swab-2, HIV-positives had lower alpha diversity (P <= 0.04) and altered composition, with fewer Firmicutes and more Fusobacteria taxa (P <= 0.03), not completely attributable to very low CD4(+) cell count (median 232 cells/mu l), prior AIDS clinical diagnosis (N = 17), or trimethoprim-sulfamethoxazole use (N = 6). Similar but weaker differences were observed in swab-1 (HIV-positive median 580 CD4(+) cells/mu l; no trimethoprim-sulfamethoxazole). Associations with T-cell subsets, smoking, and sexual practices were null or inconsistent. Conclusions: The anal microbiota of MSM was relatively stable over 1-5 years. However, with uncontrolled, advanced HIV infection, the microbiota had altered composition and reduced diversity partially attributable to antibiotics. Investigations of microbial community associations with other immune perturbations and clinical abnormalities are needed.
C1 [Yu, Guoqin; Goedert, James J.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Fadrosh, Doug; Ma, Bing; Ravel, Jacques] Univ Maryland, Sch Med, Inst Genom Sci, Baltimore, MD 21201 USA.
RP Goedert, JJ (reprint author), 9609 Med Ctr Dr,Room 6E106 MSC 9767, Bethesda, MD 20892 USA.
EM goedertj@mail.nih.gov
RI Ma, Bing/C-8226-2014;
OI Ma, Bing/0000-0002-3488-2393; Ravel, Jacques/0000-0002-0851-2233
FU National Cancer Institute
FX Supported in part by the Intramural Research Program of the National
Cancer Institute.
NR 29
TC 15
Z9 15
U1 1
U2 37
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
EI 1473-5571
J9 AIDS
JI Aids
PD MAR 13
PY 2014
VL 28
IS 5
BP 753
EP 760
DI 10.1097/QAD.0000000000000154
PG 8
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA AD6QU
UT WOS:000333386700013
PM 24335481
ER
PT J
AU Solomon, BD
AF Solomon, Benjamin D.
TI Incidentalomas in Genomics and Radiology
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID RECOMMENDATIONS; EXOME
AB The often-drawn analogy between incidental findings in genomics and radiology may give nonexperts a false impression of our ability to efficiently interpret genetic or genomic findings and to understand how they might affect a person's health. The availability of new technologies has made high-throughput genomic sequencing increasingly prevalent in both research and clinical fields. Such sequencing includes targeted methods, such as exome sequencing, which focuses on the functionally important regions of known genes, as well as whole-genome sequencing. As the use of these methods grows, it is important to accurately describe both their potential and their inherent challenges. One controversial area involves the handling of the range of medical information found through genomic sequencing.(1),(2) This may include genetic or genomic data that are unrelated to the primary reason for conducting sequencing but may be medically ...
C1 [Solomon, Benjamin D.] NHGRI, Med Genet Branch, Bethesda, MD 20892 USA.
[Solomon, Benjamin D.] Inova Translat Med Inst, Falls Church, VA USA.
RP Solomon, BD (reprint author), NHGRI, Med Genet Branch, Bethesda, MD 20892 USA.
NR 5
TC 14
Z9 14
U1 0
U2 4
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAR 13
PY 2014
VL 370
IS 11
BP 988
EP 990
DI 10.1056/NEJMp1310471
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA AC7ED
UT WOS:000332689100004
PM 24620864
ER
PT J
AU Beuschlein, F
Fassnacht, M
Assie, G
Calebiro, D
Stratakis, CA
Osswald, A
Ronchi, CL
Wieland, T
Sbiera, S
Faucz, FR
Schaak, K
Schmittfull, A
Schwarzmayr, T
Barreau, O
Vezzosi, D
Rizk-Rabin, M
Zabel, U
Szarek, E
Salpea, P
Forlino, A
Vetro, A
Zuffardi, O
Kisker, C
Diener, S
Meitinger, T
Lohse, MJ
Reincke, M
Bertherat, J
Strom, TM
Allolio, B
AF Beuschlein, Felix
Fassnacht, Martin
Assie, Guillaume
Calebiro, Davide
Stratakis, Constantine A.
Osswald, Andrea
Ronchi, Cristina L.
Wieland, Thomas
Sbiera, Silviu
Faucz, Fabio R.
Schaak, Katrin
Schmittfull, Anett
Schwarzmayr, Thomas
Barreau, Olivia
Vezzosi, Delphine
Rizk-Rabin, Marthe
Zabel, Ulrike
Szarek, Eva
Salpea, Paraskevi
Forlino, Antonella
Vetro, Annalisa
Zuffardi, Orsetta
Kisker, Caroline
Diener, Susanne
Meitinger, Thomas
Lohse, Martin J.
Reincke, Martin
Bertherat, Jerome
Strom, Tim M.
Allolio, Bruno
TI Constitutive Activation of PKA Catalytic Subunit in Adrenal Cushing's
Syndrome
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID PROTEIN-KINASE-A; ADRENOCORTICAL TUMORS; REGULATORY SUBUNIT; SOMATIC
MUTATIONS; CARNEY COMPLEX; GENE; HYPERPLASIA; EXPRESSION; MANAGEMENT;
RECEPTOR
AB BackgroundCorticotropin-independent Cushing's syndrome is caused by tumors or hyperplasia of the adrenal cortex. The molecular pathogenesis of cortisol-producing adrenal adenomas is not well understood.
MethodsWe performed exome sequencing of tumor-tissue specimens from 10 patients with cortisol-producing adrenal adenomas and evaluated recurrent mutations in candidate genes in an additional 171 patients with adrenocortical tumors. We also performed genomewide copy-number analysis in 35 patients with cortisol-secreting bilateral adrenal hyperplasias. We studied the effects of these genetic defects both clinically and in vitro.
ResultsExome sequencing revealed somatic mutations in PRKACA, which encodes the catalytic subunit of cyclic AMP-dependent protein kinase (protein kinase A [PKA]), in 8 of 10 adenomas (c.617AC in 7 and c.595_596insCAC in 1). Overall, PRKACA somatic mutations were identified in 22 of 59 unilateral adenomas (37%) from patients with overt Cushing's syndrome; these mutations were not detectable in 40 patients with subclinical hypercortisolism or in 82 patients with other adrenal tumors. Among 35 patients with cortisol-producing hyperplasias, 5 (including 2 first-degree relatives) carried a germline copy-number gain (duplication) of the genomic region on chromosome 19 that includes PRKACA. In vitro studies showed impaired inhibition of both PKA catalytic subunit mutants by the PKA regulatory subunit, whereas cells from patients with germline chromosomal gains showed increased protein levels of the PKA catalytic subunit; in both instances, basal PKA activity was increased.
ConclusionsGenetic alterations of the catalytic subunit of PKA were found to be associated with human disease. Germline duplications of this gene resulted in bilateral adrenal hyperplasias, whereas somatic PRKACA mutations resulted in unilateral cortisol-producing adrenal adenomas. (Funded by the European Commission Seventh Framework Program and others.)
Corticotropin-independent Cushing's syndrome occurs with adrenocortical tumors or hyperplasia. The authors report that germline duplications of PRKACA lead to bilateral adrenal hyperplasia, whereas somatic mutations lead to unilateral cortisol-producing adrenal adenomas. Endogenous hypercortisolism, referred to as Cushing's syndrome, is associated with substantial morbidity and mortality.(1) When Cushing's syndrome is severe, patients have catabolic symptoms such as muscle weakness, skin fragility, osteoporosis, and severe metabolic sequelae.(2) Hypersecretion of cortisol can be driven by an excess of pituitary or ectopic corticotropin or can be due to adrenocortical tumors or hyperplasias with corticotropin-independent cortisol production. Adrenal adenomas are common, with a prevalence of at least 3% among persons older than 50 years of age.(3) Whereas only a subset of these tumors is associated with overt Cushing's syndrome, some degree of cortisol excess is present, ...
C1 [Beuschlein, Felix; Fassnacht, Martin; Osswald, Andrea; Sbiera, Silviu; Schaak, Katrin; Reincke, Martin] Univ Munich, Med Klin & Poliklin IV, Munich, Germany.
[Meitinger, Thomas; Strom, Tim M.] Tech Univ Munich, Inst Human Genet, D-80290 Munich, Germany.
[Meitinger, Thomas; Strom, Tim M.] Munich Heart Alliance, Deutsch Zentrum Herz Kreislauf Forsch, Munich, Germany.
[Fassnacht, Martin; Sbiera, Silviu; Allolio, Bruno] Univ Wurzburg, Dept Med 1, Endocrine & Diabet Unit, Univ Hosp, D-97070 Wurzburg, Germany.
[Fassnacht, Martin; Lohse, Martin J.; Allolio, Bruno] Univ Wurzburg, Comprehens Heart Failure Ctr, D-97070 Wurzburg, Germany.
[Calebiro, Davide; Zabel, Ulrike; Lohse, Martin J.] Univ Wurzburg, Inst Pharmacol & Toxicol, D-97070 Wurzburg, Germany.
[Calebiro, Davide; Kisker, Caroline; Lohse, Martin J.] Univ Wurzburg, Rudolf Virchow Ctr, D-97070 Wurzburg, Germany.
[Calebiro, Davide; Kisker, Caroline; Lohse, Martin J.] Univ Wurzburg, Deutsch Forschungsgemeinschaft Res Ctr Expt Biome, D-97070 Wurzburg, Germany.
[Ronchi, Cristina L.] Univ Wurzburg, Comprehens Canc Ctr Mainfranken, D-97070 Wurzburg, Germany.
[Wieland, Thomas; Schmittfull, Anett; Schwarzmayr, Thomas; Diener, Susanne; Meitinger, Thomas; Strom, Tim M.] Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany.
[Assie, Guillaume; Barreau, Olivia; Vezzosi, Delphine; Rizk-Rabin, Marthe; Bertherat, Jerome] Univ Paris 05, Ctr Natl Rech Scientif, Unit Mixte Rech 8104, INSERM Unite 1016,Inst Cochin,Fac Med,Sorbonne Pa, Paris, France.
[Assie, Guillaume; Barreau, Olivia; Bertherat, Jerome] Hop Cochin, Assistance Publique Hop Paris, Referral Ctr Rare Adrenal Dis, Dept Endocrinol, F-75674 Paris, France.
[Stratakis, Constantine A.; Faucz, Fabio R.; Szarek, Eva; Salpea, Paraskevi] NICHHD, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
[Forlino, Antonella; Zuffardi, Orsetta] Univ Pavia, Dipartimento Med Mol, I-27100 Pavia, Italy.
[Vetro, Annalisa] Policlin San Matteo, Fdn Ist Ricovoro & Cura Carattere Sci, Biotechnol Res Lab, I-27100 Pavia, Italy.
RP Fassnacht, M (reprint author), Univ Hosp Wurzburg, Dept Med 1, Oberdurrbacherstr 6, D-97080 Wurzburg, Germany.
EM fassnacht_m@ukw.de
RI Lohse, Martin/A-7160-2012; Forlino, Antonella/H-5385-2015; Meitinger,
Thomas/O-1318-2015;
OI Lohse, Martin/0000-0002-0599-3510; Forlino,
Antonella/0000-0002-6385-1182; Beuschlein, Felix/0000-0001-7826-3984;
zuffardi, orsetta/0000-0002-1466-4559; calebiro,
davide/0000-0002-3811-1553; Vetro, Annalisa/0000-0003-2437-7526; Ronchi,
Cristina/0000-0001-5020-2071
FU European Commission
FX Funded by the European Commission Seventh Framework Program and others.
NR 37
TC 114
Z9 115
U1 2
U2 17
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAR 13
PY 2014
VL 370
IS 11
BP 1019
EP 1028
DI 10.1056/NEJMoa1310359
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA AC7ED
UT WOS:000332689100009
PM 24571724
ER
PT J
AU Forlino, A
Vetro, A
Garavelli, L
Ciccone, R
London, E
Stratakis, CA
Zuffardi, O
AF Forlino, Antonella
Vetro, Annalisa
Garavelli, Livia
Ciccone, Roberto
London, Edra
Stratakis, Constantine A.
Zuffardi, Orsetta
TI PRKACB and Carney Complex
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
AB The authors report that a gain of function in the catalytic subunit beta of the cyclic AMP-dependent protein kinase (protein kinase A), resulting from the presence of four copies of PRKACB (instead of the normal two), may lead to a Carney complex phenotype.To the Editor: Beuschlein et al. report a gain of function in PRKACA, the catalytic subunit alpha (C) of the cyclic AMP (cAMP)-dependent protein kinase (protein kinase A [PKA]) in cortisol-producing adenomas and micronodular adrenocortical hyperplasia.(1) Micronodular adrenocortical hyperplasia is also associated with Carney complex and inactivating mutations of the PKA regulatory subunit RI (encoded by PRKAR1A).(2),(3) We report the case of a young woman with Carney complex who presented at 19 years of age with acromegaly, pigmented spots, and myxomas (Figure 1A); she did not have Cushing's syndrome (see the Supplementary Appendix, available with the full text of ...
C1 [Forlino, Antonella; Ciccone, Roberto; Zuffardi, Orsetta] Univ Pavia, I-27100 Pavia, Italy.
[Vetro, Annalisa] Fdn Ist Ricovero & Cura Carattere Sci IRCCS Polic, Pavia, Italy.
[Garavelli, Livia] IRCCS Arcispedale S Maria Nuova, Reggio Emilia, Italy.
[London, Edra; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Forlino, A (reprint author), Univ Pavia, Via Palestro 3, I-27100 Pavia, Italy.
EM stratakc@mail.nichd.nih.gov; zuffardi@unipv.it
RI Forlino, Antonella/H-5385-2015;
OI Forlino, Antonella/0000-0002-6385-1182; Vetro,
Annalisa/0000-0003-2437-7526; zuffardi, orsetta/0000-0002-1466-4559
FU Intramural NIH HHS
NR 3
TC 27
Z9 27
U1 0
U2 2
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAR 13
PY 2014
VL 370
IS 11
BP 1065
EP 1067
DI 10.1056/NEJMc1309730
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA AC7ED
UT WOS:000332689100016
PM 24571725
ER
PT J
AU Jalah, R
Kulkarni, V
Patel, V
Rosati, M
Alicea, C
Bear, J
Yu, L
Guan, YJ
Shen, XY
Tomaras, GD
LaBranche, C
Montefiori, DC
Prattipati, R
Pinter, A
Bess, J
Lifson, JD
Reed, SG
Sardesai, NY
Venzon, DJ
Valentin, A
Pavlakis, GN
Felber, BK
AF Jalah, Rashmi
Kulkarni, Viraj
Patel, Vainav
Rosati, Margherita
Alicea, Candido
Bear, Jenifer
Yu, Lei
Guan, Yongjun
Shen, Xiaoying
Tomaras, Georgia D.
LaBranche, Celia
Montefiori, David C.
Prattipati, Rajasekhar
Pinter, Abraham
Bess, Julian, Jr.
Lifson, Jeffrey D.
Reed, Steven G.
Sardesai, Niranjan Y.
Venzon, David J.
Valentin, Antonio
Pavlakis, George N.
Felber, Barbara K.
TI DNA and Protein Co-Immunization Improves the Magnitude and Longevity of
Humoral Immune Responses in Macaques
SO PLOS ONE
LA English
DT Article
ID T-CELL RESPONSES; IMMUNODEFICIENCY VIRUS CHALLENGE; ELECTROPORATION
IN-VIVO; HIV-1 VACCINE EFFICACY; RHESUS MACAQUES; GENE-TRANSFER;
ENVELOPE GLYCOPROTEINS; SIVMAC251 CHALLENGE; B-CELL; PLASMID
AB We tested the concept of combining DNA with protein to improve anti-HIV Env systemic and mucosal humoral immune responses. Rhesus macaques were vaccinated with DNA, DNA&protein co-immunization or DNA prime followed by protein boost, and the magnitude and mucosal dissemination of the antibody responses were monitored in both plasma and mucosal secretions. We achieved induction of robust humoral responses by optimized DNA vaccination delivered by in vivo electroporation. These responses were greatly increased upon administration of a protein boost. Importantly, a co-immunization regimen of DNA&protein injected in the same muscle at the same time induced the highest systemic binding and neutralizing antibodies to homologous or heterologous Env as well as the highest Env-specific IgG in saliva. Inclusion of protein in the vaccine resulted in more immunized animals with Env-specific IgG in rectal fluids. Inclusion of DNA in the vaccine significantly increased the longevity of systemic humoral immune responses, whereas protein immunization, either as the only vaccine component or as boost after DNA prime, was followed by a great decline of humoral immune responses overtime. We conclude that DNA&protein co-delivery in a simple vaccine regimen combines the strength of each vaccine component, resulting in improved magnitude, extended longevity and increased mucosal dissemination of the induced antibodies in immunized rhesus macaques.
C1 [Jalah, Rashmi; Kulkarni, Viraj; Alicea, Candido; Felber, Barbara K.] NCI, Human Retrovirus Pathogenesis Sect, Frederick, MD 21701 USA.
[Patel, Vainav; Rosati, Margherita; Bear, Jenifer; Valentin, Antonio; Pavlakis, George N.] NCI, Human Retrovirus Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21701 USA.
[Yu, Lei; Guan, Yongjun] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Inst Human Virol, Baltimore, MD 21201 USA.
[Shen, Xiaoying; Tomaras, Georgia D.] Duke Univ, Duke Human Vaccine Inst, Durham, NC USA.
[Shen, Xiaoying; Tomaras, Georgia D.] Duke Univ, Dept Surg, Durham, NC USA.
[Shen, Xiaoying; Tomaras, Georgia D.] Duke Univ, Dept Immunol Mol Genet & Microbiol, Durham, NC USA.
[LaBranche, Celia; Montefiori, David C.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA.
[Prattipati, Rajasekhar; Pinter, Abraham] Univ Med & Dent New Jersey, Publ Hlth Res Inst, Newark, NJ 07103 USA.
[Bess, Julian, Jr.; Lifson, Jeffrey D.] Leidos Biomed Res Inc, AIDS & Canc Virus Program, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Reed, Steven G.] Infect Dis Res Inst, Seattle, WA USA.
[Sardesai, Niranjan Y.] Inovio Pharmaceut Inc, Blue Bell, PA USA.
[Venzon, David J.] NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Pavlakis, GN (reprint author), NCI, Human Retrovirus Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21701 USA.
EM george.pavlakis@nih.gov; barbara.felber@nih.gov
RI Tomaras, Georgia/J-5041-2016
FU Intramural Research Program of the National Cancer Institute, National
Institutes of Health (NCI/NIH); NCI/NIH [HHSN261200800001E]; National
Institute of Allergy and Infectious Diseases-NIH [HHSN27201100016C,
R01AI102718]; Institute of Human Virology Faculty Development Fund; Bill
and Melinda Gates Foundation [42387]
FX This work was supported in part by the Intramural Research Program of
the National Cancer Institute, National Institutes of Health (NCI/NIH)
(BKF and GNP); Federal funds from the NCI/NIH under Contract
HHSN261200800001E (to JDL); National Institute of Allergy and Infectious
Diseases-NIH Contract HHSN27201100016C (to GDT, XS, CL, and DCM),
National Institute of Allergy and Infectious Diseases-NIH grant
R01AI102718 (to AP), Institute of Human Virology Faculty Development
Fund (to YG) and Bill and Melinda Gates Foundation Grant #42387 (to
SGR). The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 47
TC 17
Z9 17
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 MAR 13
PY 2014
VL 9
IS 3
AR e91550
DI 10.1371/journal.pone.0091550
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC9JS
UT WOS:000332851300103
PM 24626482
ER
PT J
AU Correia, BE
Bates, JT
Loomis, RJ
Baneyx, G
Carrico, C
Jardine, JG
Rupert, P
Correnti, C
Kalyuzhniy, O
Vittal, V
Connell, MJ
Stevens, E
Schroeter, A
Chen, M
MacPherson, S
Serra, AM
Adachi, Y
Holmes, MA
Li, YX
Klevit, RE
Graham, BS
Wyatt, RT
Baker, D
Strong, RK
Crowe, JE
Johnson, PR
Schief, WR
AF Correia, Bruno E.
Bates, John T.
Loomis, Rebecca J.
Baneyx, Gretchen
Carrico, Chris
Jardine, Joseph G.
Rupert, Peter
Correnti, Colin
Kalyuzhniy, Oleksandr
Vittal, Vinayak
Connell, Mary J.
Stevens, Eric
Schroeter, Alexandria
Chen, Man
MacPherson, Skye
Serra, Andreia M.
Adachi, Yumiko
Holmes, Margaret A.
Li, Yuxing
Klevit, Rachel E.
Graham, Barney S.
Wyatt, Richard T.
Baker, David
Strong, Roland K.
Crowe, James E., Jr.
Johnson, Philip R.
Schief, William R.
TI Proof of principle for epitope-focused vaccine design
SO NATURE
LA English
DT Article
ID RESPIRATORY SYNCYTIAL VIRUS; NEUTRALIZING ANTIBODY; COMPUTATIONAL
DESIGN; SYSTEMATIC ANALYSIS; CIRCULAR-DICHROISM; GLOBAL BURDEN; PROTEIN;
MOTAVIZUMAB; SCAFFOLDS; INFECTION
AB Vaccines prevent infectious disease largely by inducing protective neutralizing antibodies against vulnerable epitopes. Several major pathogens have resisted traditional vaccine development, although vulnerable epitopes targeted by neutralizing antibodies have been identified for several such cases. Hence, new vaccine design methods to induce epitope-specific neutralizing antibodies are needed. Here we show, with a neutralization epitope from respiratory syncytial virus, that computational protein design can generate small, thermally and conformationally stable protein scaffolds that accurately mimic the viral epitope structure and induce potent neutralizing antibodies. These scaffolds represent promising leads for the research and development of a human respiratory syncytial virus vaccine needed to protect infants, young children and the elderly. More generally, the results provide proof of principle for epitope-focused and scaffold-based vaccine design, and encourage the evaluation and further development of these strategies for a variety of other vaccine targets, including antigenically highly variable pathogens such as human immunodeficiency virus and influenza.
C1 [Correia, Bruno E.; Baneyx, Gretchen; Jardine, Joseph G.; Kalyuzhniy, Oleksandr; Vittal, Vinayak; Stevens, Eric; Schroeter, Alexandria; MacPherson, Skye; Serra, Andreia M.; Adachi, Yumiko; Klevit, Rachel E.; Baker, David; Schief, William R.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
[Correia, Bruno E.] Univ Nova Lisboa, Inst Gulbenkian Ciencia, PhD Program Computat Biol, P-2780157 Oeiras, Portugal.
[Correia, Bruno E.] Univ Nova Lisboa, Inst Tecnol Quim & Biol, P-2780157 Oeiras, Portugal.
[Correia, Bruno E.] Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA.
[Bates, John T.; Crowe, James E., Jr.] Vanderbilt Univ, Vanderbilt Vaccine Ctr, Med Ctr, Nashville, TN 37232 USA.
[Loomis, Rebecca J.; Connell, Mary J.; Johnson, Philip R.] Childrens Hosp Philadelphia, Res Inst, Philadelphia, PA 19104 USA.
[Carrico, Chris; Rupert, Peter; Correnti, Colin; Strong, Roland K.] Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA.
[Jardine, Joseph G.; MacPherson, Skye; Serra, Andreia M.; Li, Yuxing; Wyatt, Richard T.; Schief, William R.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
[Jardine, Joseph G.; Kalyuzhniy, Oleksandr; MacPherson, Skye; Serra, Andreia M.; Adachi, Yumiko; Li, Yuxing; Wyatt, Richard T.; Schief, William R.] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA.
[Jardine, Joseph G.; Kalyuzhniy, Oleksandr; MacPherson, Skye; Serra, Andreia M.; Adachi, Yumiko; Li, Yuxing; Wyatt, Richard T.; Schief, William R.] Scripps Res Inst, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, La Jolla, CA 92037 USA.
[Chen, Man; Graham, Barney S.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Crowe, James E., Jr.] Vanderbilt Univ Sch Med, Dept Pathol Microbiol & Immunol, Nashville, TN 37232 USA.
[Crowe, James E., Jr.] Vanderbilt Univ Sch Med, Dept Pediat, Nashville, TN 37232 USA.
RP Schief, WR (reprint author), Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
EM schief@scripps.edu
RI Crowe, James/B-5549-2009; Cheng, Yushao/E-6256-2011; Baker,
David/K-8941-2012; Chiang, Vincent, Ming-Hsien/D-4312-2016;
OI Crowe, James/0000-0002-0049-1079; Baker, David/0000-0001-7896-6217;
Chiang, Vincent, Ming-Hsien/0000-0002-2029-7863; Carrico,
Chris/0000-0003-0939-9006; Spencer, Skye/0000-0001-9570-9634
FU Fundacao para a Ciencia e a Tecnologia [SFRH/BD/32958/2006]; National
Institutes of Health NRSA Training Grant [T32CA080416]; Children's
Hospital of Philadelphia; Bill and Melinda Gates Foundation CAVD award;
International AIDS Vaccine Initiative Neutralizing Antibody Consortium;
International AIDS Vaccine Initiative Neutralizing Antibody Center;
March of Dimes; National Institutes of Health [2T32GM007270, U54 AI
005714]; National Institute of Allergy and Infectious Diseases
[P01AI094419, 5R21AI088554, 1UM1AI100663, 1R01AI102766-01A1]; National
Institute of Allergy and Infectious Diseases from the Center for AIDS
Research, University of California, San Diego [P30AI36214]
FX We thank S. Menis, D. Kulp and D. Burton for comments on the manuscript,
Y.-E. Ban, D. Alonso and K. E. Laidig for computing assistance, E.
Gribben and R. Carnahan for assistance with mouse immunizations and C.
Slaughter for assistance in statistical analysis. Adjuplex adjuvant was
a gift from Advanced BioAdjuvants. The University of Washington has
filed patents relating to immunogens in this manuscript. Materials and
information will be provided under Materials Transfer Agreement (MTA).
Support for this work was provided by Fundacao para a Ciencia e a
Tecnologia fellowship SFRH/BD/32958/2006 (B. E. C.), National Institutes
of Health NRSA Training Grant fellowship T32CA080416 (J.G.J.), The
Children's Hospital of Philadelphia (P.R.J.), a Bill and Melinda Gates
Foundation CAVD award (W. R. S., R. K. S. and D. B.), the International
AIDS Vaccine Initiative Neutralizing Antibody Consortium (W. R. S. and
D. B.), the International AIDS Vaccine Initiative Neutralizing Antibody
Center (W. R. S. and R. T. W.), a grant from the March of Dimes
(J.E.C.), National Institutes of Health grants 2T32GM007270 (V. V.) and
U54 AI 005714 (R. E. K.), National Institute of Allergy and Infectious
Diseases grants P01AI094419 (W. R. S. and R. K. S.), 5R21AI088554 (W. R.
S.), 1UM1AI100663 (W. R. S. and R. T. W.), 1R01AI102766-01A1 (Y.L. and
R. T. W.), P30AI36214 (from the Center for AIDS Research, University of
California, San Diego, to Y.L.), and the National Institute of Allergy
and Infectious Diseases Intramural Research Program (B. S. G.). This is
manuscript 26069 from The Scripps Research Institute.
NR 39
TC 112
Z9 114
U1 18
U2 97
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 13
PY 2014
VL 507
IS 7491
BP 201
EP 206
DI 10.1038/nature12966
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC6RJ
UT WOS:000332651800032
PM 24499818
ER
PT J
AU Brun-Buisson, C
Sun, JF
Natanson, C
AF Brun-Buisson, Christian
Sun, Junfeng
Natanson, Charles
TI Mortality in Patients With Hypovolemic Shock Treated With Colloids or
Crystalloids
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Letter
ID HYDROXYETHYL STARCH; FLUID RESUSCITATION; SEVERE SEPSIS
C1 [Brun-Buisson, Christian] GH Henri Mondor, Serv Reanimat Med, F-9010 Creteil, France.
[Sun, Junfeng; Natanson, Charles] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Brun-Buisson, C (reprint author), GH Henri Mondor, Serv Reanimat Med, 51 Ave Lattre de Tassigny, F-9010 Creteil, France.
EM christian.brun-buisson@hmn.aphp.fr
NR 5
TC 5
Z9 5
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD MAR 12
PY 2014
VL 311
IS 10
BP 1068
EP 1069
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA AC5QO
UT WOS:000332575800029
PM 24618973
ER
PT J
AU Maltsev, AS
Grishaev, A
Roche, J
Zasloff, M
Bax, A
AF Maltsev, Alexander S.
Grishaev, Alexander
Roche, Julien
Zasloff, Michael
Bax, Ad
TI Improved Cross Validation of a Static Ubiquitin Structure Derived from
High Precision Residual Dipolar Couplings Measured in a Drug-Based
Liquid Crystalline Phase
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID C-13 CHEMICAL-SHIFT; MODEL-FREE ANALYSIS; PROTEIN-STRUCTURE; CORRELATED
MOTIONS; SCALAR COUPLINGS; NMR-SPECTROSCOPY; BIOMOLECULAR NMR; BACKBONE
MOTION; ORIENTED MEDIA; DYNAMICS
AB The antibiotic squalamine forms a lyotropic liquid crystal at very low concentrations in water (0.3-3.5% w/v), which remains stable over a wide range of temperature (1-40 degrees C) and pH (4-8). Squalamine is positively charged, and comparison of the alignment of ubiquitin relative to 36 previously reported alignment conditions shows that it differs substantially from most of these, but is closest to liquid crystalline cetyl pyridinium bromide. High precision residual dipolar couplings (RDCs) measured for the backbone H-1-N-15, C-13', H-1(alpha)-C-13(alpha), and C-13'-C-13(alpha) one-bond interactions in the squalamine medium fit well to the static structural model previously derived from NMR data. Inclusion into the structure refinement procedure of these RDCs, together with H-1-N-15 and H-1(alpha)-C-13(alpha) RDCs newly measured in Pf1, results in improved agreement between alignment-induced changes in C-13' chemical shift, (3)J(HNH alpha) values, and C-13(alpha)-C-13(beta) RDCs and corresponding values predicted by the structure, thereby validating the high quality of the single-conformer structural model. This result indicates that fitting of a single model to experimental data provides a better description of the average conformation than does averaging over previously reported NMR-derived ensemble representations. The latter can capture dynamic aspects of a protein, thus making the two representations valuable complements to one another.
C1 [Maltsev, Alexander S.; Grishaev, Alexander; Roche, Julien; Bax, Ad] NIDDKD, Lab Chem Phys, NIH, Bethesda, MD 20892 USA.
[Zasloff, Michael] Georgetown Univ Hosp, Washington, DC 20007 USA.
RP Bax, A (reprint author), NIDDKD, Lab Chem Phys, NIH, Bethesda, MD 20892 USA.
EM bax@nih.gov
RI Roche, Julien/O-3204-2013
OI Roche, Julien/0000-0003-3892-0200
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases; Intramural Antiviral Target Program of
the Office of the Director, NIH
FX This work was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases and by
the Intramural Antiviral Target Program of the Office of the Director,
NIH.
NR 38
TC 31
Z9 31
U1 4
U2 27
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0002-7863
J9 J AM CHEM SOC
JI J. Am. Chem. Soc.
PD MAR 12
PY 2014
VL 136
IS 10
BP 3752
EP 3755
DI 10.1021/ja4132642
PG 4
WC Chemistry, Multidisciplinary
SC Chemistry
GA AD0KJ
UT WOS:000332922600011
PM 24568736
ER
PT J
AU Goldszmid, RS
Dzutsev, A
Trinchieri, G
AF Goldszmid, Romina S.
Dzutsev, Amiran
Trinchieri, Giorgio
TI Host Immune Response to Infection and Cancer: Unexpected Commonalities
SO CELL HOST & MICROBE
LA English
DT Review
ID HEMATOPOIETIC STEM-CELLS; CHRONIC VIRAL-INFECTION; CD8(+) T-CELLS;
DENDRITIC CELLS; I INTERFERON; SUPPRESSOR-CELLS; MYELOID CELLS;
THERAPEUTIC INTERVENTION; TUMOR MICROENVIRONMENT; ANTITUMOR IMMUNITY
AB Both microbes and tumors activate innate resistance, tissue repair, and adaptive immunity. Unlike acute infection, tumor growth is initially unapparent; however, inflammation and immunity affect all phases of tumor growth from initiation to progression and dissemination. Here, we discuss the shared features involved in the immune response to infection and cancer including modulation by commensal microbiota, reactive hematopoiesis, chronic immune responses and regulatory mechanisms to prevent collateral tissue damage. This comparative analysis of immunity to infection and cancer furthers our understanding of the basic mechanisms underlying innate resistance and adaptive immunity and their translational application to the design of new therapeutic approaches.
C1 [Goldszmid, Romina S.; Dzutsev, Amiran; Trinchieri, Giorgio] NCI, Canc & Inflammat Program, Frederick, MD 21702 USA.
[Dzutsev, Amiran] Leidos Biomed Res Inc, Frederick, MD 21701 USA.
RP Trinchieri, G (reprint author), NCI, Canc & Inflammat Program, Frederick, MD 21702 USA.
EM trinchig@mail.nih.gov
FU Intramural NIH HHS [Z01 BC010793-01]
NR 102
TC 23
Z9 23
U1 1
U2 18
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1931-3128
EI 1934-6069
J9 CELL HOST MICROBE
JI Cell Host Microbe
PD MAR 12
PY 2014
VL 15
IS 3
BP 295
EP 305
DI 10.1016/j.chom.2014.02.003
PG 11
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA AD2WZ
UT WOS:000333098600008
PM 24629336
ER
PT J
AU Wu, S
Beard, WA
Pedersen, LG
Wilson, SH
AF Wu, Sangwook
Beard, William A.
Pedersen, Lee G.
Wilson, Samuel H.
TI Structural Comparison of DNA Polymerase Architecture Suggests a
Nucleotide Gateway to the Polymerase Active Site
SO CHEMICAL REVIEWS
LA English
DT Review
ID ESCHERICHIA-COLI; DEOXYRIBONUCLEIC-ACID; FAMILY POLYMERASES;
CRYSTAL-STRUCTURES; LARGE FRAGMENT; BETA; MECHANISM; FIDELITY;
REPLICATION; BINDING
C1 [Wu, Sangwook; Pedersen, Lee G.] Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA.
[Beard, William A.; Wilson, Samuel H.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Pedersen, LG (reprint author), Univ N Carolina, Dept Chem, CB 3290, Chapel Hill, NC 27599 USA.
EM lee_pedersen@unc.edu; wilson5@niehs.nih.gov
FU NIH [HL-06350, P41 RR-01081]; Intramural Research Program of the NIH,
National Institute of Environmental Health Sciences [Z01-ES050158,
Z01-ES050161]; National Institutes of Health [1U19CA105010]
FX L.G.P. acknowledges NIH grant HL-06350. This research was supported by
Research Project Numbers Z01-ES050158 and Z01-ES050161 to S.H.W. by the
Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences, and was in association with the National
Institutes of Health Grant 1U19CA105010. Structural images were produced
using the Chimera package57 from the Resource for
Biocomputing, Visualization, and Informatics at the University of
California, San Francisco (supported by NIH P41 RR-01081)
NR 57
TC 12
Z9 12
U1 2
U2 21
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0009-2665
EI 1520-6890
J9 CHEM REV
JI Chem. Rev.
PD MAR 12
PY 2014
VL 114
IS 5
BP 2759
EP 2774
DI 10.1021/cr3005179
PG 16
WC Chemistry, Multidisciplinary
SC Chemistry
GA AD0KL
UT WOS:000332922800005
PM 24359247
ER
PT J
AU Kiris, E
Wang, T
Yanpallewar, S
Dorsey, SG
Becker, J
Bavari, S
Palko, ME
Coppola, V
Tessarollo, L
AF Kiris, Erkan
Wang, Ting
Yanpallewar, Sudhirkumar
Dorsey, Susan G.
Becker, Jodi
Bavari, Sina
Palko, Mary Ellen
Coppola, Vincenzo
Tessarollo, Lino
TI TrkA In Vivo Function Is Negatively Regulated by Ubiquitination
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID NERVE GROWTH-FACTOR; FACTOR RECEPTOR TRKA; NEUROPATHIC PAIN; CELL FATE;
NEUROTROPHINS; GENE; MICE; INTERNALIZATION; ENDOCYTOSIS; DELETION
AB TrkA is a tyrosine kinase receptor required for development and survival of the peripheral nervous system. In the adult, TrkA and its ligand NGF are peripheral pain mediators, particularly in inflammatory pain states. However, how TrkA regulates the function of nociceptive neurons and whether its activity levels may lead to sensory abnormalities is still unclear. Here we report the characterization of a 3 aa (KFG) domain that negatively regulates TrkA level and function in response to NGF. Deletion of this domain in mouse causes a reduction of TrkA ubiquitination leading to an increase in TrkA protein levels and activity. The number of dorsal root ganglia neurons is not affected by the mutation. However, mutant mice have enhanced thermal sensitivity and inflammatory pain. Together, these data suggest that ubiquitination is a mechanism used in nociceptive neurons to regulate TrkA level and function. Our results may enhance our understanding of how ubiquitination affects TrkA activation following noxious thermal stimulation and inflammatory pain.
C1 [Kiris, Erkan; Wang, Ting; Yanpallewar, Sudhirkumar; Becker, Jodi; Palko, Mary Ellen; Tessarollo, Lino] NCI, Neural Dev Sect, Mouse Canc Genet Program, Frederick, MD 21702 USA.
[Kiris, Erkan; Becker, Jodi] US Army Med Res Inst Infect Dis, Dept Target Discovery & Expt Microbiol, Frederick, MD 21702 USA.
[Dorsey, Susan G.] Univ Maryland, Sch Nursing, Baltimore, MD 21201 USA.
[Dorsey, Susan G.] Univ Maryland, Program Neurosci, Baltimore, MD 21201 USA.
[Coppola, Vincenzo] Ohio State Univ, Wexner Med Ctr, Ctr Comprehens Canc, Dept MVIMG, Columbus, OH 43210 USA.
RP Coppola, V (reprint author), Ohio State Univ, Wexner Med Ctr, Ctr Comprehens Canc, Dept MVIMG, Columbus, OH 43210 USA.
EM Vincenzo.Coppola@osumc.edu; tessarol@mail.nih.gov
RI Coppola, Vincenzo/E-2917-2011
OI Coppola, Vincenzo/0000-0001-6163-1779
FU National Cancer Institute, Center for Cancer Research, National
Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Cancer Institute, Center for Cancer Research, National
Institutes of Health. We thank Eileen Southon and Susan Reid for
technical help in generating the TrkA mutant mouse model, Colleen
Barrick for technical help, and Allan Weissman for discussion and
suggestions. We are grateful to Robert Stephens for the discussions at
the start of the project and Juan Carlos Arevalo for sharing his
unpublished results.
NR 33
TC 8
Z9 8
U1 0
U2 4
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD MAR 12
PY 2014
VL 34
IS 11
BP 4090
EP 4098
DI 10.1523/JNEUROSCI.4294-13.2014
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA AC9UG
UT WOS:000332879500029
PM 24623787
ER
PT J
AU Enama, ME
Ledgerwood, JE
Novik, L
Nason, MC
Gordon, IJ
Holman, L
Bailer, RT
Roederer, M
Koup, RA
Mascola, JR
Nabel, GJ
Graham, BS
AF Enama, Mary E.
Ledgerwood, Julie E.
Novik, Laura
Nason, Martha C.
Gordon, Ingelise J.
Holman, LaSonji
Bailer, Robert T.
Roederer, Mario
Koup, Richard A.
Mascola, John R.
Nabel, Gary J.
Graham, Barney S.
CA VRC 011 Study Team
TI Phase I Randomized Clinical Trial of VRC DNA and rAd5 HIV-1 Vaccine
Delivery by Intramuscular (IM), Subcutaneous (SC) and Intradermal (ID)
Administration (VRC 011)
SO PLOS ONE
LA English
DT Article
ID T-CELL RESPONSES; CANDIDATE VACCINE; IMMUNOGENICITY EVALUATION; EFFICACY
TRIAL; VIRUS; IMMUNIZATION; INFECTION; ANTIBODY; IMMUNITY; VECTORS
AB Background: Phase 1 evaluation of the VRC HIV DNA and rAd5 vaccines delivered intramuscularly (IM) supported proceeding to a Phase 2 b efficacy study. Here we report comparison of the IM, subcutaneous (SC) and intradermal (ID) routes of administration.
Methods: Sixty subjects were randomized to 6 schedules to evaluate the IM, SC or ID route for prime injections. Three schedules included DNA primes (Wks 0,4,8) and 3 schedules included rAd5 prime (Wk0); all included rAd5 IM boost (Wk24). DNA vaccine dosage was 4 mg IM or SC, but 0.4 mg ID, while all rAd5 vaccinations were 10(10) PU. All injections were administered by needle and syringe.
Results: Overall, 27/30 subjects completed 3 DNA primes; 30/30 subjects completed rAd5 primes. Mild local pruritus (itchiness), superficial skin lesions and injection site nodules were associated with ID and SC, but not IM injections. All routes induced T-cell and antibody immune responses after rAd5 boosting. Overall, >95% had Env antibody and >80% had Env T-cell responses.
Conclusions: The pattern of local reactogenicity following ID and SC injections differed from IM injections but all routes were well-tolerated. There was no evidence of an immunogenicity advantage following SC or ID delivery, supporting IM delivery as the preferred route of administration.
C1 [Enama, Mary E.; Ledgerwood, Julie E.; Novik, Laura; Gordon, Ingelise J.; Holman, LaSonji; Bailer, Robert T.; Roederer, Mario; Koup, Richard A.; Mascola, John R.; Nabel, Gary J.; Graham, Barney S.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Nason, Martha C.] NIAID, Biostat Res Branch, Div Clin Res, NIH, Bethesda, MD 20892 USA.
RP Graham, BS (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM bgraham@nih.gov
FU U.S. Government
FX This study was supported by U.S. Government funding for the intramural
research conducted by the National Institute of Allergy and Infectious
Diseases. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 24
TC 6
Z9 6
U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 12
PY 2014
VL 9
IS 3
AR e91366
DI 10.1371/journal.pone.0091366
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC9HN
UT WOS:000332845300081
PM 24621858
ER
PT J
AU Steingrimsdottir, L
Halldorsson, TI
Siggeirsdottir, K
Cotch, MF
Einarsdottir, BO
Eiriksdottir, G
Sigurdsson, S
Launer, LJ
Harris, TB
Gudnason, V
Sigurdsson, G
AF Steingrimsdottir, Laufey
Halldorsson, Thorhallur I.
Siggeirsdottir, Kristin
Cotch, Mary Frances
Einarsdottir, Berglind O.
Eiriksdottir, Gudny
Sigurdsson, Sigurdur
Launer, Lenore J.
Harris, Tamara B.
Gudnason, Vilmundur
Sigurdsson, Gunnar
TI Hip Fractures and Bone Mineral Density in the Elderly-Importance of
Serum 25-Hydroxyvitamin D
SO PLOS ONE
LA English
DT Article
ID VITAMIN-D SUPPLEMENTATION; GENE/ENVIRONMENT SUSCEPTIBILITY-REYKJAVIK;
RANDOMIZED CONTROLLED-TRIALS; OLDER-ADULTS; OSTEOPOROTIC FRACTURES;
NONSPINE FRACTURES; MUSCLE STRENGTH; HEALTH OUTCOMES; DIETARY-INTAKE;
RISK
AB Background: The significance of serum 25-hydroxyvitamin D [25(OH) D] concentrations for hip fracture risk of the elderly is still uncertain. Difficulties reaching both frail and healthy elderly people in randomized controlled trials or large cohort studies may in part explain discordant findings. We determined hazard ratios for hip fractures of elderly men and women related to serum 25(OH) D, including both the frail and the healthy segment of the elderly population.
Methods: The AGES-Reykjavik Study is a prospective study of 5764 men and women, age 66-96 years, based on a representative sample of the population of Reykjavik, Iceland. Participation was 71.8%. Hazard ratios of incident hip fractures and baseline bone mineral density were determined according to serum concentrations of 25(OH) D at baseline.
Results: Mean follow-up was 5.4 years. Compared with referent values (50-75 nmol/L), hazard ratios for hip fractures were 2.24 (95% CI 1.63, 3.09) for serum 25(OH) D <30 nmol/L, adjusting for age, sex, body mass index, height, smoking, alcohol intake and season, and 2.08 (95% CI 1.51, 2.87), adjusting additionally for physical activity. No difference in risk was associated with 30-50 nmol/L or >= 75 nmol/L in either model compared with referent. Analyzing the sexes separately, hazard ratios were 2.61 (95% CI 1.47, 4.64) in men and 1.93 (95% CI 1.31, 2.84) in women. Values <30 nmol/L were associated with significantly lower bone mineral density of femoral neck compared with referent, z-scores -0.14 (95% CI - 0.27, -0.00) in men and -0.11 (95% CI -0.22, -0.01) in women.
Conclusions: Our results lend support to the overarching importance of maintaining serum 25(OH) D above 30 nmol/L for bone health of elderly people while potential benefits of having much higher levels could not be detected.
C1 [Steingrimsdottir, Laufey; Halldorsson, Thorhallur I.] Univ Iceland, Unit Nutr Res, Reykjavik, Iceland.
[Steingrimsdottir, Laufey; Halldorsson, Thorhallur I.] Landspitali Univ Hosp, Reykjavik, Iceland.
[Siggeirsdottir, Kristin; Einarsdottir, Berglind O.; Eiriksdottir, Gudny; Sigurdsson, Sigurdur; Gudnason, Vilmundur; Sigurdsson, Gunnar] Iceland Heart Assoc Res Inst, Kopavogur, Iceland.
[Launer, Lenore J.; Harris, Tamara B.] NIA, Intramural Res Program, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Cotch, Mary Frances] NEI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA.
[Gudnason, Vilmundur; Sigurdsson, Gunnar] Univ Iceland, Reykjavik, Iceland.
RP Steingrimsdottir, L (reprint author), Univ Iceland, Unit Nutr Res, Reykjavik, Iceland.
EM laufey@hi.is
RI Gudnason, Vilmundur/K-6885-2015; Halldorsson, Tohrhallur/M-1823-2015;
OI Gudnason, Vilmundur/0000-0001-5696-0084; Halldorsson,
Tohrhallur/0000-0001-5115-0162; Cotch, Mary Frances/0000-0002-2046-4350
FU National Institutes of Health, USA [N01-AG-12100]; National Institute on
Aging Intramural Research Program, the National Eye Institute USA
[Z01-EY000401]; National Institutes of Health, Hjartavernd (The
Icelandic Heart Association); Althingi (Icelandic Parliament)
FX This study was funded by the National Institutes of Health, USA contract
N01-AG-12100, and the National Institute on Aging Intramural Research
Program, the National Eye Institute USA (Z01-EY000401), National
Institutes of Health, Hjartavernd (The Icelandic Heart Association), and
Althingi (Icelandic Parliament). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 42
TC 4
Z9 4
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 12
PY 2014
VL 9
IS 3
AR e91122
DI 10.1371/journal.pone.0091122
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC9HN
UT WOS:000332845300054
PM 24621578
ER
PT J
AU Connor, EM
Smoyer, WE
Davis, JM
Zajicek, A
Ulrich, L
Purucker, M
Hirschfeld, S
AF Connor, Edward M.
Smoyer, William E.
Davis, Jonathan M.
Zajicek, Anne
Ulrich, Linda
Purucker, Mary
Hirschfeld, Steven
TI Meeting the Demand for Pediatric Clinical Trials
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Editorial Material
AB High-quality, cost-ef ective pediatric clinical trials require a robust research and regulatory infrastructure and a properly trained workforce.
C1 [Connor, Edward M.] George Washington Univ, Dept Pediat, Washington, DC 20010 USA.
[Connor, Edward M.] George Washington Univ, Clin & Translat Sci Inst, Washington, DC 20010 USA.
[Connor, Edward M.] George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20010 USA.
[Smoyer, William E.] Ohio State Univ, Nationwide Childrens Hosp, Res Inst, Ctr Clin & Translat Res, Columbus, OH 43205 USA.
[Smoyer, William E.] Ohio State Univ, Dept Pediat, Columbus, OH 43205 USA.
[Davis, Jonathan M.] Tufts Med Ctr, Floating Hosp Children, Dept Pediat, Boston, MA 02111 USA.
[Davis, Jonathan M.] Tufts Med Ctr, Floating Hosp Children, Tufts Clin & Translat Sci Inst, Boston, MA 02111 USA.
[Zajicek, Anne; Hirschfeld, Steven] Eunice Kennedy Shriver NICHD, Bethesda, MD 20892 USA.
[Ulrich, Linda] US FDA, Off Orphan Prod Dev, Silver Spring, MD 20993 USA.
[Purucker, Mary] NCATS, CTSA, Bethesda, MD 20892 USA.
RP Connor, EM (reprint author), George Washington Univ, Dept Pediat, Washington, DC 20010 USA.
EM econnor@childrensnational.org
RI Hirschfeld, Steven/E-2987-2016
OI Hirschfeld, Steven/0000-0003-0627-7249
FU NCATS NIH HHS [UL1 TR000073, UL1 TR000075, UL1 TR001070, UL1TR000073,
UL1TR000075, UL1TR001070]
NR 7
TC 6
Z9 6
U1 0
U2 2
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
EI 1946-6242
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD MAR 12
PY 2014
VL 6
IS 227
AR 227fs11
DI 10.1126/scitranslmed.3008043
PG 3
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA AC6KD
UT WOS:000332630500001
PM 24622511
ER
PT J
AU Cooley, BC
Nevado, J
Mellad, J
Yang, D
St Hilaire, C
Negro, A
Fang, F
Chen, GB
San, H
Walts, AD
Schwartzbeck, RL
Taylor, B
Lanzer, JD
Wragg, A
Elagha, A
Beltran, LE
Berry, C
Feil, R
Virmani, R
Ladich, E
Kovacic, JC
Boehm, M
AF Cooley, Brian C.
Nevado, Jose
Mellad, Jason
Yang, Dan
St Hilaire, Cynthia
Negro, Alejandra
Fang, Fang
Chen, Guibin
San, Hong
Walts, Avram D.
Schwartzbeck, Robin L.
Taylor, Brandi
Lanzer, Jan D.
Wragg, Andrew
Elagha, Abdalla
Beltran, Leilani E.
Berry, Colin
Feil, Robert
Virmani, Renu
Ladich, Elena
Kovacic, Jason C.
Boehm, Manfred
TI TGF-beta Signaling Mediates Endothelial-to-Mesenchymal Transition
(EndMT) During Vein Graft Remodeling
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID SMOOTH-MUSCLE-CELLS; NEOINTIMAL FORMATION; INTIMAL HYPERPLASIA; IN-VIVO;
FIBROSIS; MICE; EXPRESSION; DISEASE; MODEL; GENE
AB Veins grafted into an arterial environment undergo a complex vascular remodeling process. Pathologic vascular remodeling often results in stenosed or occluded conduit grafts. Understanding this complex process is important for improving the outcome of patients with coronary and peripheral artery disease undergoing surgical revascularization. Using in vivo murine cell lineage-tracing models, we show that endothelial-derived cells contribute to neointimal formation through endothelial-to-mesenchymal transition (EndMT), which is dependent on early activation of the Smad2/3-Slug signaling pathway. Antagonism of transforming growth factor-beta (TGF-beta) signaling by TGF-beta neutralizing antibody, short hairpin RNA-mediated Smad3 or Smad2 knockdown, Smad3 haploinsufficiency, or endothelial cell-specific Smad2 deletion resulted in decreased EndMT and less neointimal formation compared to controls. Histological examination of postmortem human vein graft tissue corroborated the changes observed in our mouse vein graft model, suggesting that EndMT is operative during human vein graft remodeling. These data establish that EndMT is an important mechanism underlying neointimal formation in interpositional vein grafts, and identifies the TGF-beta-Smad2/3-Slug signaling pathway as a potential therapeutic target to prevent clinical vein graft stenosis.
C1 [Cooley, Brian C.] Med Coll Wisconsin, Dept Orthopaed Surg, Milwaukee, WI 53226 USA.
[Nevado, Jose] Univ Philippines, Coll Med, Natl Inst Hlth, Manila 1000, Philippines.
[Nevado, Jose; Yang, Dan; St Hilaire, Cynthia; Negro, Alejandra; Fang, Fang; Chen, Guibin; San, Hong; Walts, Avram D.; Schwartzbeck, Robin L.; Taylor, Brandi; Lanzer, Jan D.; Wragg, Andrew; Elagha, Abdalla; Beltran, Leilani E.; Berry, Colin; Kovacic, Jason C.; Boehm, Manfred] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA.
[Mellad, Jason; Wragg, Andrew] Barts & London NHS Trust, William Harvey Res Inst, London EC1M 6BQ, England.
[Elagha, Abdalla] Cairo Univ, Fac Med, Cardiovasc Dept, Cairo 11559, Egypt.
[Berry, Colin] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow G12 8TA, Lanark, Scotland.
[Feil, Robert] Univ Tubingen, Interfac Inst Biochem, D-72074 Tubingen, Germany.
[Virmani, Renu; Ladich, Elena] CVPath Inst Inc, Gaithersburg, MD 20878 USA.
[Kovacic, Jason C.] Icahn Sch Med,Mt, Zena & Michael A Wiener Cardiovasc Inst, New York, NY 10029 USA.
RP Boehm, M (reprint author), Univ N Carolina, Dept Pathol, Chapel Hill, NC 27599 USA.
EM boehmm@nhlbi.nih.gov
RI St. Hilaire, Cynthia/I-4713-2014; Feil, Robert/B-8918-2014;
OI Feil, Robert/0000-0002-7335-4841; Elagha, Abdalla/0000-0003-3136-2293
FU Intramural Research Program of the NHLBI; Commission on Higher
Education; Philippine Council on Advanced Science and Technology
Research and Development, Department of Science and Technology
(PCASTRD-DOST) in the Philippines; NIH [K08HL111330]; Boehringer
Ingelheim Fonds
FX This project was funded by the Intramural Research Program of the NHLBI.
J.N. was supported by the Commission on Higher Education and the
Philippine Council on Advanced Science and Technology Research and
Development, Department of Science and Technology (PCASTRD-DOST) in the
Philippines. J.M. was supported by an NIH Marshall Scholarship. J.C.K.
is supported by NIH grant K08HL111330. J.D.L. was supported by a
Boehringer Ingelheim Fonds MD Fellowship.
NR 40
TC 20
Z9 20
U1 0
U2 12
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
EI 1946-6242
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD MAR 12
PY 2014
VL 6
IS 227
AR 227ra34
DI 10.1126/scitranslmed.3006927
PG 12
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA AC6KD
UT WOS:000332630500006
PM 24622514
ER
PT J
AU Barber, MD
Brubaker, L
Burgio, KL
Richter, HE
Nygaard, I
Weidner, AC
Menefee, SA
Lukacz, ES
Norton, P
Schaffer, J
Nguyen, JN
Borello-France, D
Goode, PS
Jakus-Waldman, S
Spino, C
Warren, LK
Gantz, MG
Meikle, SF
AF Barber, Matthew D.
Brubaker, Linda
Burgio, Kathryn L.
Richter, Holly E.
Nygaard, Ingrid
Weidner, Alison C.
Menefee, Shawn A.
Lukacz, Emily S.
Norton, Peggy
Schaffer, Joseph
Nguyen, John N.
Borello-France, Diane
Goode, Patricia S.
Jakus-Waldman, Sharon
Spino, Cathie
Warren, Lauren Klein
Gantz, Marie G.
Meikle, Susan F.
CA Eunice Kennedy Shriver Natl Inst C
TI Comparison of 2 Transvaginal Surgical Approaches and Perioperative
Behavioral Therapy for Apical Vaginal Prolapse The OPTIMAL Randomized
Trial
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID PELVIC ORGAN PROLAPSE; SACROSPINOUS LIGAMENT FIXATION; URGE
URINARY-INCONTINENCE; CONSERVATIVE TREATMENT; STRESS-INCONTINENCE;
CLINICAL-TRIALS; VAULT PROLAPSE; UNITED-STATES; WOMEN; SURGERY
AB IMPORTANCE More than 300 000 surgeries are performed annually in the United States for pelvic organ prolapse. Sacrospinous ligament fixation (SSLF) and uterosacral ligament suspension (ULS) are commonly performed transvaginal surgeries to correct apical prolapse. Little is known about their comparative efficacy and safety, and it is unknown whether perioperative behavioral therapy with pelvic floor muscle training (BPMT) improves outcomes of prolapse surgery.
OBJECTIVE To compare outcomes between (1) SSLF and ULS and (2) perioperative BPMT and usual care in women undergoing surgery for vaginal prolapse and stress urinary incontinence.
DESIGN, SETTING, AND PARTICIPANTS Multicenter, 2 x 2 factorial, randomized trial of 374 women undergoing surgery to treat both apical vaginal prolapse and stress urinary incontinence was conducted between 2008 and 2013 at 9 US medical centers. Two-year follow-up rate was 84.5%.
INTERVENTIONS The surgical intervention was transvaginal surgery including midurethral sling with randomization to SSLF (n = 186) or ULS (n = 188); the behavioral intervention was randomization to receive perioperative BPMT (n = 186) or usual care (n = 188).
MAIN OUTCOMES AND MEASURES The primary outcome for the surgical intervention (surgical success) was defined as (1) no apical descent greater than one-third into vaginal canal or anterior or posterior vaginal wall beyond the hymen (anatomic success), (2) no bothersome vaginal bulge symptoms, and (3) no re-treatment for prolapse at 2 years. For the behavioral intervention, primary outcome at 6 months was urinary symptom scores (Urinary Distress Inventory; range 0-300, higher scores worse), and primary outcomes at 2 years were prolapse symptom scores (Pelvic Organ Prolapse Distress Inventory; range 0-300, higher scores worse) and anatomic success.
RESULTS At 2 years, surgical group was not significantly associated with surgical success rates (ULS, 59.2%[93/157] vs SSLF, 60.5%[92/152]; unadjusted difference, -1.3%; 95% CI, -12.2% to 9.6%; adjusted odds ratio [OR], 0.9; 95% CI, 0.6 to 1.5) or serious adverse event rates (ULS, 16.5%[31/188] vs SSLF, 16.7%[31/186]; unadjusted difference, -0.2%; 95% CI, -7.7% to 7.4%; adjusted OR, 0.9; 95% CI, 0.5 to 1.6). Perioperative BPMT was not associated with greater improvements in urinary scores at 6 months (adjusted treatment difference, -6.7; 95% CI, -19.7 to 6.2), prolapse scores at 24 months (adjusted treatment difference, -8.0; 95% CI, -22.1 to 6.1), or anatomic success at 24 months.
CONCLUSIONS AND RELEVANCE Two years after vaginal surgery for prolapse and stress urinary incontinence, neither ULS nor SSLF was significantly superior to the other for anatomic, functional, or adverse event outcomes. Perioperative BPMT did not improve urinary symptoms at 6 months or prolapse outcomes at 2 years.
C1 [Barber, Matthew D.] Cleveland Clin, Obstet Gynecol & Womens Hlth Inst, Cleveland, OH 44195 USA.
[Brubaker, Linda] Loyola Univ, Dept Obstet & Gynecol, Stritch Sch Med, Chicago, IL 60611 USA.
[Brubaker, Linda] Loyola Univ, Dept Urol, Stritch Sch Med, Chicago, IL 60611 USA.
[Burgio, Kathryn L.; Goode, Patricia S.] Univ Alabama Birmingham, Div Gerontol Geriatr & Palliat Care, Birmingham, AL USA.
[Burgio, Kathryn L.; Goode, Patricia S.] Dept Vet Affairs, Birmingham, AL USA.
[Richter, Holly E.] Univ Alabama Birmingham, Dept Obstet & Gynecol, Birmingham, AL USA.
[Nygaard, Ingrid; Norton, Peggy] Univ Utah, Med Ctr, Dept Obstet & Gynecol, Salt Lake City, UT 84132 USA.
[Weidner, Alison C.] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA.
[Menefee, Shawn A.] Kaiser Permanente So Calif, Dept Obstet & Gynecol, San Diego, CA USA.
[Lukacz, Emily S.] Univ Calif San Diego Hlth Syst, Dept Reprod Med, San Diego, CA USA.
[Schaffer, Joseph] Univ Texas SW Med Ctr Dallas, Dept Obstet & Gynecol, Dallas, TX 75390 USA.
[Nguyen, John N.; Jakus-Waldman, Sharon] Kaiser Permanente So Calif, Dept Obstet & Gynecol, Downey, CA USA.
[Borello-France, Diane] Duquesne Univ, Dept Phys Therapy, Pittsburgh, PA 15219 USA.
[Spino, Cathie] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
[Warren, Lauren Klein; Gantz, Marie G.] RTI Int, Social Stat & Environm Sci, Res Triangle Pk, NC USA.
[Meikle, Susan F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Barber, MD (reprint author), Cleveland Clin, Obstet Gynecol & Womens Hlth Inst, 9500 Euclid Ave,Desk A81, Cleveland, OH 44195 USA.
EM barberm2@ccf.org
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [U01 HD041249, U10 HD041250, U10 HD041261, U10 HD041267, U10
HD054136, U10 HD054214, U10 HD054215, U01 HD069031, U10 HD054241];
National Institutes of Health Office of Research on Women's Health
FX This research was supported by grants U01 HD041249, U10 HD041250, U10
HD041261, U10 HD041267, U10 HD054136, U10 HD054214, U10 HD054215, U01
HD069031, and U10 HD054241 from the Eunice Kennedy Shriver National
Institute of Child Health and Human Development and the National
Institutes of Health Office of Research on Women's Health.
NR 38
TC 47
Z9 48
U1 1
U2 6
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD MAR 12
PY 2014
VL 311
IS 10
BP 1023
EP 1034
DI 10.1001/jama.2014.1719
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA AC5QO
UT WOS:000332575800020
PM 24618964
ER
PT J
AU Batters, C
Veigel, C
Homsher, E
Sellers, JR
AF Batters, Christopher
Veigel, Claudia
Homsher, Earl
Sellers, James R.
TI To understand muscle you must take it apartle
SO FRONTIERS IN PHYSIOLOGY
LA English
DT Review
DE muscle; myosin; actomyosin; ATPase; electron microscopy; in vitro model
ID MYOSIN MOTOR DOMAIN; FAMILIAL HYPERTROPHIC CARDIOMYOPATHY; BETA-CARDIAC
MYOSIN; DEPENDENT ADENOSINE-TRIPHOSPHATASE; RABBIT SKELETAL ACTOMYOSIN;
ESSENTIAL LIGHT-CHAIN; ACTIN-BASED MOTOR; S2 HINGE REGIONS;
HAND-OVER-HAND; SMOOTH-MUSCLE
AB Striated muscle is an elegant system for study at many levels. Much has been learned about the mechanism of contraction from studying the mechanical properties of intact and permeabilized (or skinned) muscle fibers. Structural studies using electron microscopy, X-ray diffraction or spectroscopic probes attached to various contractile proteins were possible because of the highly ordered sarcomeric arrangement of actin and myosin. However, to understand the mechanism of force generation at a molecular level, it is necessary to take the system apart and study the interaction of myosin with actin using in vitro assays. This reductionist approach has lead to many fundamental insights into how myosin powers muscle contraction. In addition, nature has provided scientists with an array of muscles with different mechanical properties and with a superfamily of myosin molecules. Taking advantage of this diversity in myosin structure and function has lead to additional insights into common properties of force generation. This review will highlight the development of the major assays and methods that have allowed this combined reductionist and comparative approach to be so fruitful. This review highlights the history of biochemical and biophysical studies of myosin and demonstrates how a broad comparative approach combined with reductionist studies have led to a detailed understanding of how myosin interacts with actin and uses chemical energy to generate force and movement in muscle contraction and motility in general.
C1 [Batters, Christopher; Veigel, Claudia] Univ Munich, Dept Cellular Physiol, Munich, Germany.
[Batters, Christopher; Veigel, Claudia] Univ Munich, Ctr Nanosci CeNS, Munich, Germany.
[Homsher, Earl] Univ Calif Los Angeles, Dept Physiol, Los Angeles, CA 90024 USA.
[Sellers, James R.] NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA.
RP Sellers, JR (reprint author), NHLBI, Lab Mol Physiol, NIH, Bldg 50,Room 3523, Bethesda, MD 20892 USA.
EM sellersj@nhlbi.nih.gov
NR 157
TC 5
Z9 5
U1 4
U2 19
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1664-042X
J9 FRONT PHYSIOL
JI Front. Physiol.
PD MAR 11
PY 2014
VL 5
AR 90
DI 10.3389/fphys.2014.00090
PG 14
WC Physiology
SC Physiology
GA AX3KX
UT WOS:000346839300001
PM 24653704
ER
PT J
AU Klein, CJ
Wu, YH
Vogel, P
Goebel, HH
Bonnemann, C
Zukosky, K
Botuyan, MV
Duan, XH
Middha, S
Atkinson, EJ
Mer, G
Dyck, PJ
AF Klein, Christopher J.
Wu, Yanhong
Vogel, Peter
Goebel, Hans H.
Boennemann, Carsten
Zukosky, Kristen
Botuyan, Maria-Victoria
Duan, Xiaohui
Middha, Sumit
Atkinson, Elizabeth J.
Mer, Georges
Dyck, Peter J.
TI Ubiquitin ligase defect by DCAF8 mutation causes HMSN2 with giant axons
SO NEUROLOGY
LA English
DT Article
ID MARIE-TOOTH-DISEASE; NEUROFILAMENT ACCUMULATION; SEQUENCING DATA;
NEUROPATHY; GIGAXONIN; SH3TC2
AB Objective:To identify the genetic cause of axonal hereditary motor and sensory neuropathy (HMSN2) with infrequent giant axons.Methods:We studied 11 members of a previously described HMSN2 family with infrequent giant axons and variable cardiomyopathy. Whole-exome sequencing (WES) was performed on 2 affected persons and 1 unaffected person. Sanger sequencing was utilized to confirm the identified novel variant tracking with the affected status. Linkage analysis and haplotype mapping were obtained to confirm the causal nature of the identified variant. Cotransfection of HEK293 cells and co-immunoprecipitation assay were performed to assess the impact of the identified mutant protein in the implicated ubiquitin ligase pathway.Results:Giant axons with neurofilament accumulations were found in 3 affected persons who had undergone nerve biopsy evaluations. Six novel variants were identified by WES, but only DCAF8 p.R317C tracked with affected status within the family. Linkage and haplotype analysis using microsatellite markers supported this variant as causal. The mutation is within the DCAF8 WD repeat region critical for its binding to DDB1. Functional analysis shows DCAF8 p.R317C reduces the association of DCAF8 and DDB1, which is important in Cul4-ubiquitin E3 function.Conclusions:Our results indicate that DCAF8 p.R317C mutation is responsible for this specific variety of HMSN2 with infrequent giant axons and mild cardiomyopathy. This mutation results in decreased DDB1-DCAF8 association, leading to an E3 ubiquitin ligase defect that is likely associated with neurofilament degradation.
C1 [Klein, Christopher J.; Duan, Xiaohui; Dyck, Peter J.] Mayo Clin, Peripheral Nerve Lab, Rochester, MN 55905 USA.
[Wu, Yanhong] Mayo Clin, Lab Med & Pathol, Rochester, MN USA.
[Botuyan, Maria-Victoria; Mer, Georges] Mayo Clin, Dept Biochem & Mol Biol, Rochester, MN USA.
[Middha, Sumit; Atkinson, Elizabeth J.] Mayo Clin, Rochester, MN USA.
[Vogel, Peter] St Georg Hosp, Dept Neurol, Hamburg, Germany.
[Goebel, Hans H.] Charite, Dept Neuropathol, D-13353 Berlin, Germany.
[Boennemann, Carsten; Zukosky, Kristen] NINDS, Neurogenet Branch, Bethesda, MD 20892 USA.
RP Klein, CJ (reprint author), Mayo Clin, Peripheral Nerve Lab, Rochester, MN 55905 USA.
EM klein.christopher@mayo.edu
OI Middha, Sumit/0000-0003-4135-6268
FU NIH [NS065007]
FX NIH grant (NS065007, C.J.K.), Mayo Clinic Center for Individualized
Medicine.
NR 22
TC 4
Z9 5
U1 1
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD MAR 11
PY 2014
VL 82
IS 10
BP 873
EP 878
DI 10.1212/WNL.0000000000000206
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA AH9TJ
UT WOS:000336485100014
PM 24500646
ER
PT J
AU Lee, PR
Marsh, EB
AF Lee, Paul R.
Marsh, Elisabeth B.
TI Opinion & Special Articles: Mentoring in neurology Filling the residency
gap in academic mentoring
SO NEUROLOGY
LA English
DT Editorial Material
ID MEDICINE
AB Effective academic mentoring significantly affects a physician's choice of career, academic productivity, and professional trajectory. The mentoring relationship is necessary for the continued success of medical training. It is critical to cultivate a climate in which mentoring can thrive. In order to improve the quality and outcomes of mentoring, we must adopt a comprehensive plan. There are interventions at every level of training that will ensure that the current cohort of neurologists receives the requisite expertise needed to flourish and inspire future trainees. Professional organizations must articulate a comprehensive vision of mentoring. Institutions must create an infrastructure to support mentors. Mentors should work in active partnerships with their mentees to forge sustained, productive relationships. Mentees must actively contribute to their own mentoring. Proper mentorship will ensure a bright future for academic neurology.
C1 [Lee, Paul R.] NINDS, NIH, Bethesda, MD 20892 USA.
[Marsh, Elisabeth B.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
RP Marsh, EB (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
EM ebmarsh@jhmi.edu
FU Intramural NIH HHS
NR 10
TC 0
Z9 0
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD MAR 11
PY 2014
VL 82
IS 10
BP E85
EP E88
DI 10.1212/WNL.0000000000000190
PG 4
WC Clinical Neurology
SC Neurosciences & Neurology
GA AH9TJ
UT WOS:000336485100002
PM 24616198
ER
PT J
AU Han, J
Fujisawa, T
Husain, SR
Puri, RK
AF Han, Jing
Fujisawa, Toshio
Husain, Syed R.
Puri, Raj K.
TI Identification and characterization of cancer stem cells in human head
and neck squamous cell carcinoma
SO BMC CANCER
LA English
DT Article
DE HNSCC (head & neck squamous cell carcinoma); Stem-like cells; CD24;
CD44; Salivary gland malignant neoplasms
ID CD24 EXPRESSION; ALDEHYDE DEHYDROGENASE; MARKER; RESISTANCE; LINES;
IMMUNOPHENOTYPES; GEMCITABINE; METASTASIS
AB Background: Current evidence suggests that initiation, growth, and invasion of cancer are driven by a small population of cancer stem cells (CSC). Previous studies have identified CD44+ cells as cancer stem cells in head and neck squamous cell carcinoma (HNSCC). However, CD44 is widely expressed in most cells in HNSCC tumor samples and several cell lines tested. We previously identified a small population of CD24+/CD44+ cells in HNSCC. In this study, we examined whether this population of cells may represent CSC in HNSCC.
Methods: CD24+/CD44+ cells from HNSCC cell lines were sorted by flow cytometry, and their phenotype was confirmed by qRT-PCR. Their self-renewal and differentiation properties, clonogenicity in collagen gels, and response to anticancer drugs were tested in vitro. The tumorigenicity potential of CD24+/CD44+ cells was tested in athymic nude mice in vivo.
Results: Our results show that CD24+/CD44+ cells possessed stemness characteristics of self-renewal and differentiation. CD24+/CD44+ cells showed higher cell invasion in vitro and made higher number of colonies in collagen gels compared to CD24-/CD44+ HNSCC cells. In addition, the CD24+/CD44+ cells were more chemo-resistant to gemcitabine and cisplatin compared to CD24-/CD44+ cells. In vivo, CD24+/CD44+ cells showed a tendency to generate larger tumors in nude mice compared to CD24-/CD44+ cell population.
Conclusion: Our study clearly demonstrates that a distinct small population of CD24+/CD44+ cells is present in HNSCC that shows stem cell-like properties. This distinct small population of cells should be further characterized and may provide an opportunity to target HNSCC CSC for therapy.
C1 [Han, Jing; Husain, Syed R.; Puri, Raj K.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
RP Puri, RK (reprint author), US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, NIH Bldg 29B,Rm 2NN20,29 Lincoln Dr, Bethesda, MD 20892 USA.
EM raj.puri@fda.hhs.gov
NR 39
TC 22
Z9 22
U1 1
U2 15
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2407
J9 BMC CANCER
JI BMC Cancer
PD MAR 11
PY 2014
VL 14
AR 173
DI 10.1186/1471-2407-14-173
PG 11
WC Oncology
SC Oncology
GA AD7DF
UT WOS:000333421100001
PM 24612587
ER
PT J
AU Morris, JC
Tan, AR
Olencki, TE
Shapiro, GI
Dezube, BJ
Reiss, M
Hsu, FJ
Berzofsky, JA
Lawrence, DP
AF Morris, John C.
Tan, Antoinette R.
Olencki, Thomas E.
Shapiro, Geoffrey I.
Dezube, Bruce J.
Reiss, Michael
Hsu, Frank J.
Berzofsky, Jay A.
Lawrence, Donald P.
TI Phase I Study of GC1008 (Fresolimumab): A Human Anti-Transforming Growth
Factor-Beta (TGF beta) Monoclonal Antibody in Patients with Advanced
Malignant Melanoma or Renal Cell Carcinoma
SO PLOS ONE
LA English
DT Article
ID EPITHELIAL-MESENCHYMAL TRANSDIFFERENTIATION; METASTATIC BREAST-CANCER;
SOLID TUMORS; T-CELLS; PROGRESSION; INHIBITION; EFFICACY; SURVIVAL;
VIVO; KERATOACANTHOMAS
AB Background: In advanced cancers, transforming growth factor-beta (TGFb) promotes tumor growth and metastases and suppresses host antitumor immunity. GC1008 is a human anti-TGFb monoclonal antibody that neutralizes all isoforms of TGFb. Here, the safety and activity of GC1008 was evaluated in patients with advanced malignant melanoma and renal cell carcinoma.
Methods: In this multi-center phase I trial, cohorts of patients with previously treated malignant melanoma or renal cell carcinoma received intravenous GC1008 at 0.1, 0.3, 1, 3, 10, or 15 mg/kg on days 0, 28, 42, and 56. Patients achieving at least stable disease were eligible to receive Extended Treatment consisting of 4 doses of GC1008 every 2 weeks for up to 2 additional courses. Pharmacokinetic and exploratory biomarker assessments were performed.
Results: Twenty-nine patients, 28 with malignant melanoma and 1 with renal cell carcinoma, were enrolled and treated, 22 in the dose-escalation part and 7 in a safety cohort expansion. No dose-limiting toxicity was observed, and the maximum dose, 15 mg/kg, was determined to be safe. The development of reversible cutaneous keratoacanthomas/squamous-cell carcinomas (4 patients) and hyperkeratosis was the major adverse event observed. One malignant melanoma patient achieved a partial response, and six had stable disease with a median progression-free survival of 24 weeks for these 7 patients (range, 16.4-44.4 weeks).
Conclusions: GC1008 had no dose-limiting toxicity up to 15 mg/kg. In patients with advanced malignant melanoma and renal cell carcinoma, multiple doses of GC1008 demonstrated acceptable safety and preliminary evidence of antitumor activity, warranting further studies of single agent and combination treatments.
C1 [Morris, John C.; Berzofsky, Jay A.] NCI, Vaccine Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Morris, John C.; Berzofsky, Jay A.] NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Tan, Antoinette R.; Reiss, Michael] Canc Inst New Jersey, Dept Med, New Brunswick, NJ USA.
[Olencki, Thomas E.] Ohio State Univ, Dept Med, Columbus, OH 43210 USA.
[Shapiro, Geoffrey I.] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA.
[Dezube, Bruce J.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA.
[Hsu, Frank J.] Genzyme Corp, Cambridge, MA USA.
[Lawrence, Donald P.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
RP Morris, JC (reprint author), Univ Cincinnati, Dept Med, Div Hematol Oncol, Vontz Ctr Mol Studies, ML0562, Cincinnati, OH 45221 USA.
EM morri2j7@ucmail.uc.edu; berzofsj@mail.nih.gov
FU Genzyme Corporation; Center for Cancer Research, National Cancer
Institute (NCI); Genzyme
FX This work was supported by Genzyme Corporation, and in part by the
Intramural Research Program of the Center for Cancer Research, National
Cancer Institute (NCI). Genzyme provided financial support, the
investigational agent GC1008, and supported study design, data
collection and analysis, the decision to publish, and preparation of the
manuscript.
NR 50
TC 41
Z9 46
U1 1
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 11
PY 2014
VL 9
IS 3
AR e90353
DI 10.1371/journal.pone.0090353
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC9GM
UT WOS:000332842400014
PM 24618589
ER
PT J
AU Harel, A
Kravitz, DJ
Baker, CI
AF Harel, Assaf
Kravitz, Dwight J.
Baker, Chris I.
TI Task context impacts visual object processing differentially across the
cortex
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE object recognition; vision; fMRI; top-down processing; occipitotemporal
cortex
ID INFERIOR PREFRONTAL CORTEX; HUMAN FRONTOPARIETAL CORTEX; LATERAL
OCCIPITAL COMPLEX; PARIETAL CORTEX; FUNCTIONAL MRI; WORKING-MEMORY; FMRI
EVIDENCE; ATTENTIONAL MODULATION; EXTRASTRIATE CORTEX; FOCAL ATTENTION
AB Perception reflects an integration of "bottom-up" (sensory-driven) and "top-down" (internally generated) signals. Although models of visual processing often emphasize the central role of feed-forward hierarchical processing, less is known about the impact of top-down signals on complex visual representations. Here, we investigated whether and how the observer's goals modulate object processing across the cortex. We examined responses elicited by a diverse set of objects under six distinct tasks, focusing on either physical (e.g., color) or conceptual properties (e.g., man-made). Critically, the same stimuli were presented in all tasks, allowing us to investigate how task impacts the neural representations of identical visual input. We found that task has an extensive and differential impact on object processing across the cortex. First, we found task-dependent representations in the ventral temporal and prefrontal cortex. In particular, although object identity could be decoded from the multivoxel response within task, there was a significant reduction in decoding across tasks. In contrast, the early visual cortex evidenced equivalent decoding within and across tasks, indicating task-independent representations. Second, task information was pervasive and present from the earliest stages of object processing. However, although the responses of the ventral temporal, prefrontal, and parietal cortex enabled decoding of both the type of task (physical/conceptual) and the specific task (e.g., color), the early visual cortex was not sensitive to type of task and could only be used to decode individual physical tasks. Thus, object processing is highly influenced by the behavioral goal of the observer, highlighting how top-down signals constrain and inform the formation of visual representations.
C1 [Harel, Assaf; Kravitz, Dwight J.; Baker, Chris I.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
RP Harel, A (reprint author), NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
EM assaf.harel@nih.gov
OI Baker, Chris/0000-0001-6861-8964; Harel, Assaf/0000-0002-4899-6156
NR 74
TC 36
Z9 36
U1 5
U2 20
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAR 11
PY 2014
VL 111
IS 10
BP E962
EP E971
DI 10.1073/pnas.1312567111
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC5MK
UT WOS:000332564800014
PM 24567402
ER
PT J
AU Fekete, A
Eszenyi, D
Herczeg, M
Pozsgay, V
Borbas, A
AF Fekete, Aniko
Eszenyi, Daniel
Herczeg, Mihaly
Pozsgay, Vince
Borbas, Aniko
TI Preparation of synthetic oligosaccharide- conjugates of poly-beta-(1 ->
6)-N-acetyl glucosamine
SO CARBOHYDRATE RESEARCH
LA English
DT Article
DE Carbohydrate chemical synthesis; poly-beta-(1 -> 6)-N-acetyl
glucosamine; Reductive amination; Glycoconjugate
ID POLY-N-ACETYLGLUCOSAMINE; SURFACE POLYSACCHARIDE; STAPHYLOCOCCUS-AUREUS;
INTERCELLULAR ADHESIN; OLIGOGLUCOSAMINES; EPIDERMIDIS; RESISTANCE;
PATHOGENS; VACCINES
AB Staphylococcus aureus and Staphylococcus epidermidis are prominent bacterial pathogens of nosocomial infections. Both microorganisms colonize medical devices by forming adherent biofilms. poly-beta-(1 -> 6)-N-acetyl-glucosamine (PNAG) is a surface polysaccharide antigen which was found on both S. aureus and S. epidermidis. Animal studies have proved that PNAG can elicit antibodies which protect against staphylococcal infections. We have presented the synthesis of di-, tetra-and hexasaccharide fragments of PNAG with formyl-heptyl aglycone and their attachment to bovine serum albumin (BSA) by reductive amination. (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Fekete, Aniko; Herczeg, Mihaly] Univ Debrecen, Dept Organ Chem, H-4010 Debrecen, Hungary.
[Pozsgay, Vince] NICHHD, NIH, Bethesda, MD 20892 USA.
[Eszenyi, Daniel; Borbas, Aniko] Univ Debrecen, Dept Pharmaceut Chem, Med & Hlth Ctr, H-4010 Debrecen, Hungary.
RP Fekete, A (reprint author), Univ Debrecen, Dept Organ Chem, POB 20, H-4010 Debrecen, Hungary.
EM fekete.aniko@science.unideb.hu
FU Hungarian Scientific Research Fund [PD73064]
FX This work was supported by the Hungarian Scientific Research Fund
(Project No. PD73064).
NR 28
TC 4
Z9 5
U1 0
U2 13
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0008-6215
EI 1873-426X
J9 CARBOHYD RES
JI Carbohydr. Res.
PD MAR 11
PY 2014
VL 386
BP 33
EP 40
DI 10.1016/j.carres.2013.12.022
PG 8
WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic
SC Biochemistry & Molecular Biology; Chemistry
GA AA5YM
UT WOS:000331175800006
PM 24468971
ER
PT J
AU van Ryn, M
Phelan, SM
Arora, NK
Haggstrom, DA
Jackson, GL
Zafar, SY
Griffin, JM
Zullig, LL
Provenzale, D
Yeazel, MW
Jindal, RM
Clauser, SB
AF van Ryn, Michelle
Phelan, Sean M.
Arora, Neeraj K.
Haggstrom, David A.
Jackson, George L.
Zafar, S. Yousuf
Griffin, Joan M.
Zullig, Leah L.
Provenzale, Dawn
Yeazel, Mark W.
Jindal, Rahul M.
Clauser, Steven B.
TI Patient-Reported Quality of Supportive Care Among Patients With
Colorectal Cancer in the Veterans Affairs Health Care System
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID CELL LUNG-CANCER; OF-LIFE; DISTRESS MANAGEMENT; PROSTATE-CANCER; NCCN
GUIDELINES; RECALL BIAS; DISPARITIES; ONCOLOGY; COMMUNICATION;
COORDINATION
AB Purpose High-quality supportive care is an essential component of comprehensive cancer care. We implemented a patient-centered quality of cancer care survey to examine and identify predictors of quality of supportive care for bowel problems, pain, fatigue, depression, and other symptoms among 1,109 patients with colorectal cancer.
Patients and Methods Patients with new diagnosis of colorectal cancer at any Veterans Health Administration medical center nationwide in 2008 were ascertained through the Veterans Affairs Central Cancer Registry and sent questionnaires assessing a variety of aspects of patient-centered cancer care. We received questionnaires from 63% of eligible patients (N = 1,109). Descriptive analyses characterizing patient experiences with supportive care and binary logistic regression models were used to examine predictors of receipt of help wanted for each of the five symptom categories.
Results There were significant gaps in patient-centered quality of supportive care, beginning with symptom assessment. In multivariable modeling, the impact of clinical factors and patient race on odds of receiving wanted help varied by symptom. Coordination of care quality predicted receipt of wanted help for all symptoms, independent of patient demographic or clinical characteristics.
Conclusion This study revealed substantial gaps in patient-centered quality of care, difficult to characterize through quality measurement relying on medical record review alone. It established the feasibility of collecting patient-reported quality measures. Improving quality measurement of supportive care and implementing patient-reported outcomes in quality-measurement systems are high priorities for improving the processes and outcomes of care for patients with cancer.
C1 [van Ryn, Michelle; Phelan, Sean M.] Mayo Clin, Rochester, MN 55905 USA.
[Griffin, Joan M.] Vet Affairs Med Ctr, Durham, NC USA.
[Yeazel, Mark W.] Univ Minnesota, Minneapolis, MN USA.
[Arora, Neeraj K.; Clauser, Steven B.] NCI, Bethesda, MD 20892 USA.
[Haggstrom, David A.] Richard L Roudebush Vet Affairs Med Ctr, Indianapolis, IN 46202 USA.
[Haggstrom, David A.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
[Jackson, George L.; Zullig, Leah L.; Provenzale, Dawn] Durham Vet Affairs Med Ctr, Durham, NC USA.
[Jackson, George L.; Zafar, S. Yousuf; Provenzale, Dawn] Duke Univ, Med Ctr, Durham, NC 27706 USA.
[Zullig, Leah L.] Univ N Carolina, Chapel Hill, NC USA.
[Jindal, Rahul M.] Walter Reed Army Med Ctr, Washington, DC 20307 USA.
RP van Ryn, M (reprint author), Mayo Clin, Div Hlth Care Policy & Res, 200 First St SW, Rochester, MN 55905 USA.
EM vanryn.michelle@mayo.edu
FU Interagency Quality of Cancer Care Committee, Applied Research Branch,
National Cancer Institute (NCI); Veterans Health Administration; NCI
[5R25CA116339]
FX Supported by the Interagency Quality of Cancer Care Committee, Applied
Research Branch, National Cancer Institute (NCI), through an interagency
agreement with the Veterans Health Administration and by NCI Grant No.
5R25CA116339 (L.L.Z.).
NR 62
TC 12
Z9 12
U1 1
U2 3
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 10
PY 2014
VL 32
IS 8
BP 809
EP +
DI 10.1200/JCO.2013.49.4302
PG 8
WC Oncology
SC Oncology
GA AC4IB
UT WOS:000332483400018
PM 24493712
ER
PT J
AU Lu, KH
Wood, ME
Daniels, M
Burke, C
Ford, J
Kauff, ND
Kohlmann, W
Lindor, NM
Mulvey, TM
Robinson, L
Rubinstein, WS
Stoffel, EM
Snyder, C
Syngal, S
Merrill, JK
Wollins, DS
Hughes, KS
AF Lu, Karen H.
Wood, Marie E.
Daniels, Molly
Burke, Cathy
Ford, James
Kauff, Noah D.
Kohlmann, Wendy
Lindor, Noralane M.
Mulvey, Therese M.
Robinson, Linda
Rubinstein, Wendy S.
Stoffel, Elena M.
Snyder, Carrie
Syngal, Sapna
Merrill, Janette K.
Wollins, Dana Swartzberg
Hughes, Kevin S.
TI American Society of Clinical Oncology Expert Statement: Collection and
Use of a Cancer Family History for Oncology Providers
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID LI-FRAUMENI SYNDROME; COLORECTAL-CANCER; RISK-ASSESSMENT;
LYNCH-SYNDROME; POLICY STATEMENT; BREAST-CANCER; GENETIC COUNSELORS;
GERMLINE MUTATIONS; NATIONAL SOCIETY; OVARIAN-CANCER
C1 [Lu, Karen H.; Daniels, Molly; Burke, Cathy] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Robinson, Linda] Simmons Comprehens Canc Ctr, Dallas, TX USA.
[Wood, Marie E.] Univ Vermont, Burlington, VT 05405 USA.
[Ford, James] Stanford Univ, Med Ctr, Stanford, CA 94305 USA.
[Kauff, Noah D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Kohlmann, Wendy] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA.
[Lindor, Noralane M.] Mayo Clin, Scottsdale, AZ USA.
[Mulvey, Therese M.] Southcoast Ctr Canc Care, Fall River, MA USA.
[Syngal, Sapna] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Hughes, Kevin S.] Massachusetts Gen Hosp, Avon Comprehens Breast Evaluat Ctr, Boston, MA 02114 USA.
[Rubinstein, Wendy S.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
[Stoffel, Elena M.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Snyder, Carrie] Creighton Univ, Omaha, NE 68178 USA.
[Merrill, Janette K.; Wollins, Dana Swartzberg] Amer Soc Clin Oncol, Alexandria, VA USA.
RP Wood, ME (reprint author), Univ Vermont, Hem Onc, Given E214,89 Beaumont, Burlington, VT 05405 USA.
EM marie.wood@uvm.edu
OI Daniels, Molly/0000-0002-5093-5539; Kauff, Noah/0000-0001-7242-6156;
Hughes, Kevin/0000-0003-4084-6484
FU NCI NIH HHS [P50 CA083639, P30 CA016672]
NR 51
TC 43
Z9 46
U1 1
U2 3
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 10
PY 2014
VL 32
IS 8
BP 833
EP +
DI 10.1200/JCO.2013.50.9257
PG 9
WC Oncology
SC Oncology
GA AC4IB
UT WOS:000332483400022
PM 24493721
ER
PT J
AU Freidlin, B
Sun, ZX
Gray, R
Korn, EL
AF Freidlin, Boris
Sun, Zhuoxin
Gray, Robert
Korn, Edward L.
TI Reply to S. Goteti et al
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Letter
ID RANDOMIZED CLINICAL-TRIALS; ONCOLOGY
C1 [Freidlin, Boris; Korn, Edward L.] NCI, Bethesda, MD 20892 USA.
[Sun, Zhuoxin; Gray, Robert] Dana Farber Canc Inst, Eastern Cooperat Oncol Grp, Boston, MA 02115 USA.
RP Freidlin, B (reprint author), NCI, Bethesda, MD 20892 USA.
NR 8
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 10
PY 2014
VL 32
IS 8
BP 856
EP 856
DI 10.1200/JCO.2013.53.8934
PG 1
WC Oncology
SC Oncology
GA AC4IB
UT WOS:000332483400029
PM 24493728
ER
PT J
AU Murphy, E
Steenbergen, C
AF Murphy, Elizabeth
Steenbergen, Charles
TI Estrogen regulation of protein expression and signaling pathways in the
heart
SO BIOLOGY OF SEX DIFFERENCES
LA English
DT Review
DE Cardiac; Estrogen; Ischemia-reperfusion; Metabolism
ID ISCHEMIA-REPERFUSION INJURY; PRESSURE-OVERLOAD HYPERTROPHY; TERM CALORIC
RESTRICTION; MALE-FEMALE DIFFERENCES; RECEPTOR-ALPHA;
GENDER-DIFFERENCES; MOUSE HEART; ER-BETA; ISCHEMIA/REPERFUSION INJURY;
TRIACYLGLYCERIDE DYNAMICS
AB Sex differences in cardiovascular disease and cardiac physiology have been reported in humans as well as in animal models. Premenopausal women have reduced cardiovascular disease compared to men, but the incidence of cardiovascular disease in women increases following menopause. Sex differences in cardiomyocytes likely contribute to the differences in male-female physiology and response to disease. Sex differences in the heart have been noted in electrophysiology, contractility, signaling, metabolism, and cardioprotection. These differences appear to be due, at least in part, to differences in gene and protein expression as well as in posttranslational protein modifications. This review will focus primarily on estrogen-mediated male-female differences in protein expression and signaling pathways in the heart and cardiac cells. It should be emphasized that these basic differences are not intrinsically beneficial or detrimental per se; the difference can be good or bad depending on the context and circumstances.
C1 [Murphy, Elizabeth] NHLBI, Lab Cardiac Physiol, Syst Biol Ctr, NIH, Bethesda, MD 20824 USA.
[Steenbergen, Charles] JHMI, Dept Pathol, Baltimore, MD 21231 USA.
RP Murphy, E (reprint author), NHLBI, Lab Cardiac Physiol, Syst Biol Ctr, NIH, Bethesda, MD 20824 USA.
EM murphy1@mail.nih.gov
FU ZIA [HL002065, HL006059]; [5R01 HL039752]
FX EM was supported by ZIA HL002065 and ZIA HL006059. CS was supported by
5R01 HL039752.
NR 81
TC 10
Z9 10
U1 1
U2 11
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2042-6410
J9 BIOL SEX DIFFER
JI Biol. Sex Differ.
PD MAR 10
PY 2014
VL 5
AR 6
DI 10.1186/2042-6410-5-6
PG 7
WC Endocrinology & Metabolism; Genetics & Heredity
SC Endocrinology & Metabolism; Genetics & Heredity
GA AE0OD
UT WOS:000333664700001
PM 24612699
ER
PT J
AU Pusapati, GV
Hughes, CE
Dorn, KV
Zhang, DP
Sugianto, P
Aravind, L
Rohatgi, R
AF Pusapati, Ganesh V.
Hughes, Casey E.
Dorn, Karolin V.
Zhang, Dapeng
Sugianto, Priscilla
Aravind, L.
Rohatgi, Rajat
TI EFCAB7 and IQCE Regulate Hedgehog Signaling by Tethering the EVC-EVC2
Complex to the Base of Primary Cilia
SO DEVELOPMENTAL CELL
LA English
DT Article
ID VAN-CREVELD-SYNDROME; WEYERS ACRODENTAL DYSOSTOSIS; PROTEOMIC ANALYSIS;
PROTEINS; DISSOCIATION; MUTATIONS; INTERACTS; EVC/EVC2; EVC
AB The Hedgehog (Hh) pathway depends on primary cilia in vertebrates, but the signaling machinery within cilia remains incompletely defined. We report the identification of a complex between two ciliary proteins, EFCAB7 and IQCE, which positively regulates the Hh pathway. The EFCAB7-IQCE module anchors the EVC-EVC2 complex in a signaling microdomain at the base of cilia. EVC and EVC2 genes are mutated in Ellis van Creveld and Weyers syndromes, characterized by impaired Hh signaling in skeletal, cardiac, and orofacial tissues. EFCAB7 binds to a C-terminal disordered region in EVC2 that is deleted in Weyers patients. EFCAB7 depletion mimics the Weyers cellular phenotype-the mislocalization of EVC-EVC2 within cilia and impaired activation of the transcription factor GLI2. Evolutionary analysis suggests that emergence of these complexes might have been important for adaptation of an ancient organelle, the cilium, for an animal-specific signaling network.
C1 [Pusapati, Ganesh V.; Hughes, Casey E.; Dorn, Karolin V.; Sugianto, Priscilla; Rohatgi, Rajat] Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA.
[Pusapati, Ganesh V.; Hughes, Casey E.; Dorn, Karolin V.; Sugianto, Priscilla; Rohatgi, Rajat] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA.
[Zhang, Dapeng; Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Aravind, L (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM aravind@ncbi.nlm.nih.gov; rrohatgi@stanford.edu
FU March of Dimes Foundation [6-FY13-104]; National Institutes of Health
[DP2GM105448]; Pew Foundation; Sontag Foundation; Intramural Research
Program of the National Institutes of Health, Department of Health, and
Human Services
FX We thank A. Lebensohn for purification of the GBP protein used in all
the anti-GFP IP experiments and for help with the CRISPR/Cas9 system, G.
Luchetti for insightful discussions and EvC complex experiments in 293T
cells, E. Nigg (anti-CEP164) and J. Eggenschwiler (anti-GLI2) for
reagents, and X. Ge for help with immunofluorescence. This work was
supported by the March of Dimes Foundation (6-FY13-104), the National
Institutes of Health (DP2GM105448), and the Pew Foundation and the
Sontag Foundation. D.Z. and L.A. are supported by funds of the
Intramural Research Program of the National Institutes of Health,
Department of Health, and Human Services.
NR 25
TC 20
Z9 21
U1 0
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1534-5807
EI 1878-1551
J9 DEV CELL
JI Dev. Cell
PD MAR 10
PY 2014
VL 28
IS 5
BP 483
EP 496
DI 10.1016/j.devcel.2014.01.021
PG 14
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA AD6XU
UT WOS:000333405600004
PM 24582806
ER
PT J
AU Galiwango, RM
Lubyayi, L
Musoke, R
Kalibbala, S
Buwembo, M
Kasule, J
Serwadda, D
Gray, RH
Reynolds, SJ
Chang, LW
AF Galiwango, Ronald M.
Lubyayi, Lawrence
Musoke, Richard
Kalibbala, Sarah
Buwembo, Martin
Kasule, Jjingo
Serwadda, David
Gray, Ronald H.
Reynolds, Steven J.
Chang, Larry W.
TI Field Evaluation of PIMA Point-of-Care CD4 Testing in Rakai, Uganda
SO PLOS ONE
LA English
DT Article
ID ANTIRETROVIRAL THERAPY; SOUTH-AFRICA; ANALYZER; SERVICE; MORTALITY;
COUNTS
AB Objective: To assess the accuracy of PIMA Point-of-Care (POC) CD4 testing in rural Rakai, Uganda.
Methods: 903 HIV positive persons attending field clinics provided a venous blood sample assessed on site using PIMA analyzers per manufacturer's specifications. The venous samples were then run on FACSCalibur flow cytometry at a central facility. The Bland-Altman method was used to estimate mean bias and 95% limits of agreement (LOA). Sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) were calculated for a CD4 threshold of <350 and <500 cells/uL for antiretroviral eligibility.
Results: There was a high correlation between PIMA and FACSCalibur CD4 counts (r = 0.943, p<0.001). Relative to FACSCalibur, the PIMA POC CD4 had negative mean bias of -34.6 cells/uL (95% LOA: -219.8 to 150.6) overall. The dispersion at CD4<350 cells/uL was 5.1 cells/uL (95% LOA: -126.6 to 136.8). For a threshold of CD4<350 cells/uL, PIMA venous blood had a sensitivity of 88.6% (95% CI 84.8-92.4%), specificity of 87.5% (95% CI 84.9-90.1%), NPV of 94.9% (95% CI 93.1-96.7%), and PPV of 74.4% (95% CI 69.6-79.2%). PIMA sensitivity and PPV significantly increased to 96.1% and 88.3% respectively with increased threshold of 500 cells/uL.
Conclusions: Overall, PIMA POC CD4 counts demonstrated negative bias compared to FACSCalibur. PIMA POC sensitivity improved significantly at a higher CD4 threshold of 500 than a 350 cells/uL threshold.
C1 [Galiwango, Ronald M.; Lubyayi, Lawrence; Musoke, Richard; Kalibbala, Sarah; Buwembo, Martin; Kasule, Jjingo] Rakai Hlth Sci Program, Kalisizo, Uganda.
[Gray, Ronald H.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Reynolds, Steven J.] NIAID, Immunoregulat Lab, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Reynolds, Steven J.; Chang, Larry W.] Johns Hopkins Univ, Sch Med, Dept Med, Div Infect Dis, Baltimore, MD 21205 USA.
[Serwadda, David] Makerere Univ, Coll Hlth Sci, Sch Publ Hlth, Kampala, Uganda.
RP Chang, LW (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Div Infect Dis, Baltimore, MD 21205 USA.
EM lchang8@jhmi.edu
FU CDC Uganda; PEPFAR Uganda; Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health
FX We acknowledge CDC Uganda for the funding support that availed the PIMAs
to our institution and PEPFAR Uganda that supports the treatment
program. This work was supported in part (SJR) by the Division of
Intramural Research, National Institute of Allergy and Infectious
Diseases, National Institutes of Health. The funders had no role in the
study design, data collection, analysis, decision to publish or
preparation of the manuscript.
NR 18
TC 10
Z9 10
U1 1
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 10
PY 2014
VL 9
IS 3
AR e88928
DI 10.1371/journal.pone.0088928
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC9FH
UT WOS:000332839300008
PM 24614083
ER
PT J
AU Thein, S
Tao-Cheng, JH
Li, Y
Bayer, KU
Reese, TS
Dosemeci, A
AF Thein, Soe
Tao-Cheng, Jung-Hwa
Li, Yan
Bayer, K. Ulrich
Reese, Thomas S.
Dosemeci, Ayse
TI CaMKII Mediates Recruitment and Activation of the Deubiquitinase CYLD at
the Postsynaptic Density
SO PLOS ONE
LA English
DT Article
ID PROTEIN-KINASE-II; HIPPOCAMPAL-NEURONS; PHOSPHORYLATION; UBIQUITINATION;
DEGRADATION; INHIBITOR; PROTEASOMES; STARGAZIN; MECHANISM; PROMOTES
AB NMDA treatment of cultured hippocampal neurons causes recruitment of CYLD, as well as CaMKII, to the postsynaptic density (PSD), as shown by immunoelectron microscopy. Recruitment of CYLD, a deubiquitinase specific for K63-linked polyubiquitins, is blocked by pre-treatment with tatCN21, a CaMKII inhibitor, at a concentration that inhibits the translocation of CaMKII to the PSD. Furthermore, CaMKII co-immunoprecipitates with CYLD from solubilized PSD fractions, indicating an association between the proteins. Purified CaMKII phosphorylates CYLD on at least three residues (S-362, S-418, and S-772 on the human CYLD protein Q9NQC7-1) and promotes its deubiquitinase activity. Activation of CaMKII in isolated PSDs promotes phosphorylation of CYLD on the same residues and also enhances endogenous deubiquitinase activity specific for K63-linked polyubiquitins. Since K63-linked polyubiquitin conjugation to proteins inhibits their interaction with proteasomes, CaMKII-mediated recruitment and upregulation of CYLD is expected to remove K63-linked polyubiquitins and facilitate proteasomal degradation at the PSD.
C1 [Thein, Soe; Reese, Thomas S.; Dosemeci, Ayse] NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA.
[Tao-Cheng, Jung-Hwa] NINDS, EM Facil, Bethesda, MD 20892 USA.
[Li, Yan] NINDS, Prot Peptide Sequencing Facil, Bethesda, MD 20892 USA.
[Bayer, K. Ulrich] Univ Colorado Denver, Sch Med, Dept Pharmacol, Aurora, CO USA.
RP Thein, S (reprint author), NINDS, Neurobiol Lab, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM theinsh@mail.nih.gov; dosemeca@mail.nih.gov
FU Intramural Research Program NINDS, National Institutes of Health (NIH);
NIH [R01 NS081248]
FX This research was supported by the Intramural Research Program NINDS,
National Institutes of Health (NIH) and NIH grant R01 NS081248 (to KUB).
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 32
TC 7
Z9 7
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 10
PY 2014
VL 9
IS 3
AR e91312
DI 10.1371/journal.pone.0091312
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC9FH
UT WOS:000332839300111
PM 24614225
ER
PT J
AU Wang, RP
Sun, PD
AF Wang, Ruipeng
Sun, Peter D.
TI Natural Killer Cell-Mediated Shedding of ULBP2
SO PLOS ONE
LA English
DT Article
ID SOLUBLE UL16-BINDING PROTEIN-2; NKG2D LIGAND EXPRESSION;
CLINICAL-SIGNIFICANCE; POOR-PROGNOSIS; CUTTING EDGE; NK CELLS; T-CELLS;
RECEPTOR; APOPTOSIS; ACTIVATION
AB UL16 binding proteins (ULBPs) are a family of cell surface proteins that are present in transformed and stressed cells and ligands for NKG2D. Soluble NKG2D ligands have been found in sera from cancer patients with their protein concentrations correlated with poor cancer prognosis. Here we show, for the first time, that human tumor cells lost their surface expression of ULBP2, but not ULBP1 and ULBP3, during NK cell-mediated cytolysis. In contrast to spontaneous shedding of NKG2D ligands, NK cytolysis-mediated shedding of ULBP2 was linked to target cell apoptosis, although both resulted from metalloproteinase cleavages. Inhibition of ULBP2 shedding by a metalloproteinase inhibitor BB-94 lead to reduced NK cell-mediated cytotoxicity and cytokine production. These results illustrate a regulation of NK cell effector functions through cytolysis-induced NKG2D ligand shedding. Consequently, compounds inhibiting NKG2D ligand shedding may offer therapeutic means to reduce excessive pathogenic NK cell activities.
C1 [Wang, Ruipeng; Sun, Peter D.] NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
RP Sun, PD (reprint author), NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
EM psun@nih.gov
FU National Institute of Allergy and Infectious Diseases
FX The funding is provided by the National Institute of Allergy and
Infectious Diseases Intramural research funding. The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 29
TC 3
Z9 4
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 10
PY 2014
VL 9
IS 3
AR e91133
DI 10.1371/journal.pone.0091133
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC9FH
UT WOS:000332839300083
PM 24614922
ER
PT J
AU Gomez-Rodriguez, J
Wohlfert, EA
Handon, R
Meylan, F
Wu, JZ
Anderson, SM
Kirby, MR
Belkaid, Y
Schwartzberg, PL
AF Gomez-Rodriguez, Julio
Wohlfert, Elizabeth A.
Handon, Robin
Meylan, Francoise
Wu, Julie Z.
Anderson, Stacie M.
Kirby, Martha R.
Belkaid, Yasmine
Schwartzberg, Pamela L.
TI Itk-mediated integration of T cell receptor and cytokine signaling
regulates the balance between Th17 and regulatory T cells
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID HYPOXIA-INDUCIBLE FACTOR-1; TRANSCRIPTION FACTORS; FATE DECISIONS;
IN-VIVO; DIFFERENTIATION; MTOR; ACTIVATION; INTERLEUKIN-2; PATHWAYS;
ANTIGEN
AB A proper balance between Th17 and T regulatory cells (T-reg cells) is critical for generating protective immune responses while minimizing autoimmunity. We show that the Tec family kinase Itk (IL2-inducible T cell kinase), a component of T cell receptor (TCR) signaling pathways, influences this balance by regulating cross talk between TCR and cytokine signaling. Under both Th17 and Treg cell differentiation conditions, Itk. (-)/(-). CD4+ T cells develop higher percentages of functional FoxP(3+) cells, associated with increased sensitivity to IL-2. Itk(-)/(-) CD4+ T cells also preferentially develop into Treg cells in vivo. We find that Itk- deficient T cells exhibit reduced TCR-induced phosphorylation of mammalian target of rapamycin (mTOR) targets, accompanied by downstream metabolic alterations. Surprisingly, Itk(-)/(-) cells also exhibit reduced IL-2-induced mTOR activation, despite increased STAT5 phosphorylation. We demonstrate that in wild-type CD4+ T cells, TCR stimulation leads to a dose-dependent repression of Pten. However, at low TCR stimulation or in the absence of Itk, Pten is not effectively repressed, thereby uncoupling STAT5 phosphorylation and phosphoinositide-3-kinase (PI3K) pathways. Moreover, Itk- deficient CD4+ T cells show impaired TCR-mediated induction of Myc and miR- 19b, known repressors of Pten. Our results demonstrate that Itk helps orchestrate positive feedback loops integrating multiple T cell signaling pathways, suggesting Itk as a potential target for altering the balance between Th17 and Treg cells.
C1 [Gomez-Rodriguez, Julio; Handon, Robin; Wu, Julie Z.; Anderson, Stacie M.; Kirby, Martha R.; Schwartzberg, Pamela L.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Wohlfert, Elizabeth A.; Belkaid, Yasmine] NIAID, Bethesda, MD 20892 USA.
[Meylan, Francoise] NIAMSD, Bethesda, MD 20892 USA.
[Wu, Julie Z.] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Schwartzberg, PL (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA.
EM pams@mail.nih.gov
FU National Human Genome Research Institute; National Institute of Allergy
and Infectious Diseases; National Institute of Arthritis and
Musculoskeletal and Skin Disease
FX This work was supported by funds from the intramural programs of the
National Human Genome Research Institute, National Institute of Allergy
and Infectious Diseases, and National Institute of Arthritis and
Musculoskeletal and Skin Diseases.
NR 60
TC 39
Z9 40
U1 5
U2 14
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
EI 1540-9538
J9 J EXP MED
JI J. Exp. Med.
PD MAR 10
PY 2014
VL 211
IS 3
BP 529
EP 543
DI 10.1084/jem.20131459
PG 15
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA AC8JH
UT WOS:000332778800012
PM 24534190
ER
PT J
AU Song, MO
Mattie, MD
Lee, CH
Freedman, JH
AF Song, Min Ok
Mattie, Michael D.
Lee, Chang-Ho
Freedman, Jonathan H.
TI The role of Nrf1 and Nrf2 in the regulation of copper-responsive
transcription
SO EXPERIMENTAL CELL RESEARCH
LA English
DT Article
DE Nrf1; Nrf2; ARE; Transcription; Copper; Metallothionein-1
ID OXIDATIVE STRESS; HEPG2 CELLS; NRF2-REGULATED GENES; INDUCIBLE
EXPRESSION; ELEMENT; ACTIVATION; TOXICITY; PATHWAY; MICE; IDENTIFICATION
AB Recent evidences indicated Nrf2 is more potent than Nrfl in the activation of antioxidant genes. However, the roles of Nrf proteins in the regulation of copper-responsive transcription have not been well addressed. We took the toxicogenomic approach and the present network and Gene Ontology analyses results showed that Nrfl and Nrf2 are distinctively involved in copper-responsive transcriptional regulation in HepG2 transcriptome. Cells deficient in either Nrfl or Nrf2 were more susceptible to copper exposure than wild type cells. Nrfl and Nrf2 null cells were transfected with the luciferase reporters containing either ARE(s) or a combination of ARE(s) and MREs, and then treated with copper. In Nrf2-null (Nrf2(-/-)) cells, copper did not activate transcription of reporter genes, whereas Nrfl deficiency did not affect copper-inducible activation. Ectopic expression of Nrf2 restored copper-inducible transcription in Nrf2(-/-) cells. However, the changes in the intrinsic mRNA levels of MT-1 in Nrf null cells following copper treatment showed that Nrfl and Nrf2 equally contributed to MT-1 activation after 4 h, while Nrfl involved more than Nrf2 following 24 h exposure. These results suggest that while Nrf2 is crucial for MRE/ARE-mediated transcription in response to copper, Nrfl may activate MT-1 expression by a mechanism different from that Nr12 employs. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Song, Min Ok; Lee, Chang-Ho] Gangneung Wonju Natl Univ, Coll Nat Sci, Dept Biol, Gangneung Si 210702, Gangwon Do, South Korea.
[Mattie, Michael D.] Duke Univ, Nicholas Sch Environm, Durham, NC 27708 USA.
[Freedman, Jonathan H.] NIEHS, Lab Toxicol & Pharmacol, Res Triangle Pk, NC 27709 USA.
RP Song, MO (reprint author), Agensys Inc, 1545 17th St, Santa Monica, CA 90404 USA.
EM rotisong@gmail.com; mmattie@agensys.com
FU Intramural Research Program of the National Institute of Environmental
Health Sciences, National Institutes of Health [Z01ES102046]; Natural
Science Research Institute of Gangneung-Wonju National University
FX The authors would like to thank Dr. Glen Andrews (University of Kansas
Medical Center) for providing the mouse MT-1-based Luc reporter plasmids
and Dr. Jefferson Y. Chan (University of California-Irvine) for the Nrfl
and Nrf2-1- cell lines. This work was supported in part by the
Intramural Research Program of the National Institute of Environmental
Health Sciences, National Institutes of Health (Z01ES102046) and by
Natural Science Research Institute of Gangneung-Wonju National
University (to C.-H. Lee).
NR 37
TC 12
Z9 12
U1 0
U2 9
PU ELSEVIER INC
PI SAN DIEGO
PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4827
EI 1090-2422
J9 EXP CELL RES
JI Exp. Cell Res.
PD MAR 10
PY 2014
VL 322
IS 1
BP 39
EP 50
DI 10.1016/j.yexcr.2014.01.013
PG 12
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA AB8QU
UT WOS:000332055900005
PM 24462598
ER
PT J
AU Lyu, XM
Fang, WY
Cai, LM
Zheng, H
Ye, YF
Zhang, L
Li, JB
Peng, H
Cho, WCS
Wang, EN
Marincola, FM
Yao, KT
Cai, HB
Li, JL
Li, X
AF Lyu, Xiaoming
Fang, Weiyi
Cai, Longmei
Zheng, Hang
Ye, Yanfen
Zhang, Lan
Li, Jinbang
Peng, Hong
Cho, William C. S.
Wang, Ena
Marincola, Francesco M.
Yao, Kaitai
Cai, Hongbing
Li, Jiliang
Li, Xin
TI TGF beta R2 is a major target of miR-93 in nasopharyngeal carcinoma
aggressiveness
SO MOLECULAR CANCER
LA English
DT Article
DE miR-93; TGF beta R2; Aggressiveness; PI3K/Akt; Nasopharyngeal carcinoma
ID FACTOR-BETA RECEPTOR; OVARIAN-CANCER CELLS; TGF-BETA; GROWTH-FACTOR;
HEPATOCELLULAR-CARCINOMA; BREAST-CANCER; MESENCHYMAL TRANSITION;
MICRORNA CLUSTER; TUMOR-SUPPRESSOR; COLON-CANCER
AB Background: MiR-17-92 cluster and its paralogues have emerged as crucial regulators of many oncogenes and tumor suppressors. Transforming growth factor-beta receptor II (TGF beta R2), as an important tumor suppressor, is involved in various cancer types. However, it is in cancer that only two miRNAs of this cluster and its paralogues have been reported so far to regulate TGF beta R2. MiR-93 is oncogenic, but its targetome in cancer has not been fully defined. The role of miR-93 in nasopharyngeal carcinoma (NPC) still remains largely unknown.
Methods: We firstly evaluated the clinical signature of TGF beta R2 down-regulation in clinical samples, and next used a miRNA expression profiling analysis followed by multi-validations, including Luciferase reporter assay, to identify miRNAs targeting TGF beta R2 in NPC. In vitro and in vivo studies were performed to further investigate the effects of miRNA-mediated TGF beta R2 down-regulation on NPC aggressiveness. Finally, mechanism studies were conducted to explore the associated pathway and genes influenced by this miRNA-mediated TGF beta R2 down-regulation.
Results: TGF beta R2 was down-regulated in more than 50% of NPC patients. It is an unfavorable prognosis factor contributing to clinical NPC aggressiveness. A cluster set of 4 TGF beta R2-associated miRNAs was identified; they are all from miR-17-92 cluster and its paralogues, of which miR-93 was one of the most significant miRNAs, directly targeting TGF beta R2, promoting cell proliferation, invasion and metastasis in vitro and in vivo. Moreover, miR-93 resulted in the attenuation of Smad-dependent TGF-beta signaling and the activation of PI3K/Akt pathway by suppressing TGF beta R2, further promoting NPC cell uncontrolled growth, invasion, metastasis and EMT-like process. Impressively, the knockdown of TGF beta R2 by siRNA displayed a consentaneous phenocopy with the effect of miR-93 in NPC cells, supporting TGF beta R2 is a major target of miR-93. Our findings were also substantiated by investigation of the clinical signatures of miR-93 and TGF beta R2 in NPC.
Conclusion: The present study reports an involvement of miR-93-mediated TGF beta R2 down-regulation in NPC aggressiveness, thus giving extended insights into molecular mechanisms underlying cancer aggressiveness. Approaches aimed at blocking miR-93 may serve as a promising therapeutic strategy for treating NPC patients.
C1 [Lyu, Xiaoming; Fang, Weiyi; Cai, Longmei; Zheng, Hang; Ye, Yanfen; Li, Jinbang; Yao, Kaitai; Li, Xin] Southern Med Univ, Canc Res Inst, Guangzhou, Guangdong, Peoples R China.
[Lyu, Xiaoming; Fang, Weiyi; Cai, Longmei; Zheng, Hang; Ye, Yanfen; Li, Jinbang; Yao, Kaitai; Li, Xin] Southern Med Univ, Prov Key Lab Funct Prote, Guangzhou, Guangdong, Peoples R China.
[Cai, Hongbing] Southern Med Univ, Sch Chinese Tradit Med, Guangzhou, Guangdong, Peoples R China.
[Zhang, Lan; Peng, Hong] Southern Med Univ, Nanfang Hosp, Dept Otorhinolaryngol, Guangzhou, Guangdong, Peoples R China.
[Zheng, Hang] Southern Med Univ, Nanfang Hosp, Dept Oncol, Guangzhou, Guangdong, Peoples R China.
[Cho, William C. S.] Queen Elizabeth Hosp, Dept Clin Oncol, Guangzhou, Hong Kong, Peoples R China.
[Wang, Ena; Marincola, Francesco M.] NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Li, Jiliang] Southern Med Univ, Sch Biotechnol, Guangzhou, Guangdong, Peoples R China.
[Li, Jiliang] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Mol Oncol Labs,Dept Oncol, Oxford OX3 9DU, England.
RP Cai, HB (reprint author), Southern Med Univ, Sch Chinese Tradit Med, Guangzhou, Guangdong, Peoples R China.
EM chbing2008@126.com; ji-liang.li@imm.ox.ac.uk; xinli268@gmail.com
FU National Natural Science Foundation of China [30973292, 30872856,
30371535, 81171959]; Natural Science Foundation of Guangdong Province
[S2011010004157, S2013010016388]
FX This work was financially supported by grants from National Natural
Science Foundation of China (No. 30973292, No. 30872856, No. 30371535
and No. 81171959) and Natural Science Foundation of Guangdong Province
(No. S2011010004157 and No. S2013010016388). In addition, we appreciate
Miss. CunCun Yuan, Mr. Yaoyong Lu, and Dr. Ying He to provide helpful
technical assistances in the present study.
NR 70
TC 30
Z9 31
U1 0
U2 11
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1476-4598
J9 MOL CANCER
JI Mol. Cancer
PD MAR 8
PY 2014
VL 13
AR 51
DI 10.1186/1476-4598-13-51
PG 14
WC Biochemistry & Molecular Biology; Oncology
SC Biochemistry & Molecular Biology; Oncology
GA AF2KY
UT WOS:000334542200001
PM 24606633
ER
PT J
AU Lee, KP
Choi, S
Hong, JH
Ahuja, M
Graham, S
Ma, R
So, I
Shin, DM
Muallem, S
Yuan, JP
AF Lee, Kyu Pil
Choi, Seok
Hong, Jeong Hee
Ahuja, Malini
Graham, Sarabeth
Ma, Rong
So, Insuk
Shin, Dong Min
Muallem, Shmuel
Yuan, Joseph P.
TI Molecular Determinants Mediating Gating of Transient Receptor Potential
Canonical (TRPC) Channels by Stromal Interaction Molecule 1 (STIM1)
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Calcium; Calcium Signaling; Gating; Signaling; TRP Channels; Gating
Mechanism; STIM1
ID STORE-OPERATED CHANNELS; PLASMA-MEMBRANE; ORAI CHANNELS; CA2+ INFLUX;
MECHANISTIC INSIGHTS; CRAC CHANNELS; DOMAIN; ENTRY; CALCIUM;
OLIGOMERIZATION
AB Background: STIM1 gates TRPC channels, but the interacting domains are unknown. Results: The TRPC N and C terminus coiled coil domains interact to restrict access of STIM1. Their dissociation by cell stimulation promotes STIM1 interaction. Conclusion: The STIM1 Orai1-activating region (SOAR) domain interacts with the TRPC C terminus CCD to open the channels. Significance: The findings reveal how STIM1 opens the TRPC channels to control receptor-stimulated Ca2+ influx.
Transient receptor potential canonical (TRPC) channels mediate a critical part of the receptor-evoked Ca2+ influx. TRPCs are gated open by the endoplasmic reticulum Ca2+ sensor STIM1. Here we asked which stromal interaction molecule 1 (STIM1) and TRPC domains mediate the interaction between them and how this interaction is used to open the channels. We report that the STIM1 Orai1-activating region domain of STIM1 interacts with the TRPC channel coiled coil domains (CCDs) and that this interaction is essential for opening the channels by STIM1. Thus, disruption of the N-terminal (NT) CCDs by triple mutations eliminated TRPC surface localization and reduced binding of STIM1 to TRPC1 and TRPC5 while increasing binding to TRPC3 and TRPC6. Single mutations in TRPC1 NT or C-terminal (CT) CCDs reduced interaction and activation of TRPC1 by STIM1. Remarkably, single mutations in the TRPC3 NT CCD enhanced interaction and regulation by STIM1. Disruption in the TRPC3 CT CCD eliminated regulation by STIM1 and the enhanced interaction caused by NT CCD mutations. The NT CCD mutations converted TRPC3 from a TRPC1-dependent to a TRPC1-independent, STIM1-regulated channel. TRPC1 reduced the FRET between BFP-TRPC3 and TRPC3-YFP and between CFP-TRPC3-YFP upon stimulation. Accordingly, knockdown of TRPC1 made TRPC3 STIM1-independent. STIM1 dependence of TRPC3 was reconstituted by the TRPC1 CT CCD alone. Knockout of Trpc1 and Trpc3 similarly inhibited Ca2+ influx, and inhibition of Trpc3 had no further effect on Ca2+ influx in Trpc1(-/-) cells. Cell stimulation enhanced the formation of Trpc1-Stim1-Trpc3 complexes. These findings support a model in which the TRPC3 NT and CT CCDs interact to shield the CT CCD from interaction with STIM1. The TRPC1 CT CCD dissociates this interaction to allow the STIM1 Orai1-activating region within STIM1 access to the TRPC3 CT CCD and regulation of TRPC3 by STIM1. These studies provide evidence that the TRPC channel CCDs participate in channel gating.
C1 [Lee, Kyu Pil] Chungnam Natl Univ, Coll Vet Med, Dept Physiol, Taejon 305764, South Korea.
[Choi, Seok; Hong, Jeong Hee; Ahuja, Malini; Muallem, Shmuel] NIDCR, Epithelial Signaling & Transport Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA.
[Graham, Sarabeth; Ma, Rong; Yuan, Joseph P.] Univ N Texas, Hlth Sci Ctr, Cardiovasc Res Inst, Dept Integrat Physiol, Ft Worth, TX 76107 USA.
[So, Insuk] Seoul Natl Univ, Coll Med, Dept Physiol & Biophys, Seoul 110799, South Korea.
[Shin, Dong Min] Yonsei Univ, Dept Oral Biol, PLUS Project BK21, Seoul 120752, South Korea.
[Choi, Seok] Chosun Univ, Coll Med, Dept Physiol, Kwangju 501759, South Korea.
RP Muallem, S (reprint author), NIDCR, Epithelial Signaling & Transport Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA.
EM shmuel.muallem@nih.gov
RI rchnds, rchnds/D-7595-2016
FU National Institute of Health [Z1A-DE000735, Z01-ES101684, 5R00HL093297];
National Research Foundation of Korea (NRF) [NRF-2013R1A1A1010783,
20070056092, 2012R1A2A1A01003487]; Korean government
FX This work was funded, in whole or in part, by intramural National
Institute of Health grant Z1A-DE000735 (to S. M.); National Institutes
of Health Grant Z01-ES101684 (to L. B.); and National Institutes of
Health Grant 5R00HL093297 (to J. P. Y.). This work was also supported by
National Research Foundation of Korea (NRF) grants (MSIP)
NRF-2013R1A1A1010783 (to K. P. L.) and 20070056092 and
2012R1A2A1A01003487 (to D. M. S.) funded by the Korean government.
NR 34
TC 28
Z9 28
U1 2
U2 9
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAR 7
PY 2014
VL 289
IS 10
BP 6372
EP 6382
DI 10.1074/jbc.M113.546556
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AC3BG
UT WOS:000332389400006
PM 24464579
ER
PT J
AU Chawla, LS
Amdur, RL
Shaw, AD
Faselis, C
Palant, CE
Kimmel, PL
AF Chawla, Lakhmir S.
Amdur, Richard L.
Shaw, Andrew D.
Faselis, Charles
Palant, Carlos E.
Kimmel, Paul L.
TI Association between AKI and Long-Term Renal and Cardiovascular Outcomes
in United States Veterans
SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID ACUTE KIDNEY INJURY; ACUTE MYOCARDIAL-INFARCTION; CRITICALLY-ILL
PATIENTS; CARDIAC-SURGERY; CLINICAL-TRIALS; NIDDK WORKSHOP; FAILURE;
MORTALITY; DISEASE; RISK
AB Background and objectives
AKI is associated with major adverse kidney events (MAKE): death, new dialysis, and worsened renal function. CKD (arising from worsened renal function) is associated with a higher risk of major adverse cardiac events (MACE): myocardial infarction (MI), stroke, and heart failure. Therefore, the study hypothesis was that veterans who develop AKI during hospitalization for an MI would be at higher risk of subsequent MACE and MAKE.
Design, setting, participants, & measurements
Patients in the Veterans Affairs (VA) database who had a discharge diagnosis with International Classification of Diseases, Ninth Revision, code of 584.xx (AKI) or 410.xx (MI) and were admitted to a VA facility from October 1999 through December 2005 were selected for analysis. Three groups of patients were created on the basis of the index admission diagnosis and serum creatinine values: AKI, MI, or MI with AKI. Patients with mean baseline estimated GFR<45 ml/min per 1.73 m(2) were excluded. The primary outcomes assessed were mortality, MAKE, and MACE during the study period (maximum of 6 years). The combination of MAKE and MACE-major adverse renocardiovascular events (MARCE)-was also assessed.
Results
A total of 36,980 patients were available for analysis. Mean age +/- SD was 66.8 +/- 11.4 years. The most deaths occurred in the MI+AKI group (57.5%), and the fewest (32.3%) occurred in patients with an uncomplicated MI admission. In both the unadjusted and adjusted time-to-event analyses, patients with AKI and AKI+MI had worse MARCE outcomes than those who had MI alone (adjusted hazard ratios, 1.37 [95% confidence interval, 1.32 to 1.42] and 1.92 [1.86 to 1.99], respectively).
Conclusions
Veterans who develop AKI in the setting of MI have worse long-term outcomes than those with AKI or MI alone. Veterans with AKI alone have worse outcomes than those diagnosed with an MI in the absence of AKI.
C1 [Chawla, Lakhmir S.; Amdur, Richard L.; Faselis, Charles; Palant, Carlos E.] Vet Affairs Med Ctr, Res & Med Serv, Washington, DC 20422 USA.
[Chawla, Lakhmir S.] George Washington Univ, Dept Med, Div Renal Dis & Hypertens, Washington, DC USA.
[Chawla, Lakhmir S.] George Washington Univ, Dept Anesthesiol & Crit Care Med, Washington, DC USA.
[Amdur, Richard L.] Georgetown Univ, Sch Med, Dept Psychiat, Washington, DC USA.
[Amdur, Richard L.] Georgetown Univ, Sch Med, Dept Surg, Washington, DC USA.
[Shaw, Andrew D.] Duke Univ, Med Ctr, Dept Anesthesiol, Durham, NC 27710 USA.
[Shaw, Andrew D.] Vet Affairs Med Ctr, Durham, NC USA.
[Kimmel, Paul L.] NIDDK, NIH, Bethesda, MD 20892 USA.
RP Chawla, LS (reprint author), 900 23rd St NW,G-105, Washington, DC 20037 USA.
EM chawla@gwu.edu
NR 42
TC 58
Z9 60
U1 0
U2 1
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1555-9041
EI 1555-905X
J9 CLIN J AM SOC NEPHRO
JI Clin. J. Am. Soc. Nephrol.
PD MAR 7
PY 2014
VL 9
IS 3
BP 448
EP 456
DI 10.2215/CJN.02440213
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA AC4VD
UT WOS:000332518300006
PM 24311708
ER
PT J
AU Sajgo, S
Ghinia, MG
Shi, M
Liu, P
Dong, LJ
Parmhans, N
Popescu, O
Badea, TC
AF Sajgo, Szilard
Ghinia, Miruna Georgiana
Shi, Melody
Liu, Pinghu
Dong, Lijin
Parmhans, Nadia
Popescu, Octavian
Badea, Tudor Constantin
TI Dre - Cre Sequential Recombination Provides New Tools for Retinal
Ganglion Cell Labeling and Manipulation in Mice
SO PLOS ONE
LA English
DT Article
ID SITE-SPECIFIC RECOMBINATION; TRANSCRIPTION FACTORS BRN3A; TRANSGENIC
MOUSE LINE; MEDIATED RECOMBINATION; DNA RECOMBINATION; MAMMALIAN-CELLS;
COMBINATORIAL EXPRESSION; SOMATOSENSORY NEURONS; FLUORESCENT PROTEINS;
COMPETENCE STATE
AB Background: Genetic targeting methods have greatly advanced our understanding of many of the 20 Retinal Ganglion Cell (RGC) types conveying visual information from the eyes to the brain. However, the complexity and partial overlap of gene expression patterns in RGCs call for genetic intersectional or sparse labeling strategies. Loci carrying the Cre recombinase in conjunction with conditional knock-out, reporter or other genetic tools can be used for targeted cell type ablation and functional manipulation of specific cell populations. The three members of the Pou4f family of transcription factors, Brn3a, Brn3b and Brn3c, expressed early during RGC development and in combinatorial pattern amongst RGC types are excellent candidates for such gene manipulations.
Methods and Findings: We generated conditional Cre knock-in alleles at the Brn3a and Brn3b loci, Brn3a(CKOCre) and Brn3b(CKOCre). When crossed to mice expressing the Dre recombinase, the endogenous Brn3 gene expressed by Brn3a(CKOCre) or Brn3b(CKOCre) is removed and replaced with a Cre recombinase, generating Brn3a(Cre) and Brn3b(Cre) knock-in alleles. Surprisingly both Brn3a(Cre) and Brn3b(Cre) knock-in alleles induce early ubiquitous recombination, consistent with germline expression. However in later stages of development, their expression is limited to the expected endogenous pattern of the Brn3a and Brn3b genes. We use the Brn3a(Cre) and Brn3b(Cre) alleles to target a Cre dependent Adeno Associated Virus (AAV) reporter to RGCs and demonstrate its use in morphological characterization, early postnatal gene delivery and tracing the expression of Brn3 genes in RGCs.
Conclusions: Dre recombinase effectively recombines the Brn3a(CKOCre) and Brn3b(CKOCre) alleles containing its roxP target sites. Sequential Dre to Cre recombination reveals Brn3a and Brn3b expression in early mouse development. The generated Brn3a(Cre) and Brn3b(Cre) alleles are useful tools that can target exogenously delivered Cre dependent reagents to RGCs in early postnatal development, opening up a large range of potential applications.
C1 [Sajgo, Szilard; Ghinia, Miruna Georgiana; Shi, Melody; Liu, Pinghu; Dong, Lijin; Parmhans, Nadia; Badea, Tudor Constantin] NEI, NIH, Bethesda, MD 20892 USA.
[Sajgo, Szilard; Ghinia, Miruna Georgiana; Popescu, Octavian] Univ Babes Bolyai, Dept Biol, R-3400 Cluj Napoca, Romania.
[Popescu, Octavian] Acad Romana, Inst Biol, Bucharest, Romania.
RP Badea, TC (reprint author), NEI, NIH, Bethesda, MD 20892 USA.
EM badeatc@mail.nih.gov
FU National Institutes of Health; European Union doctoral fellowship system
through POSDRU Program [107/1.5/S/76841]
FX This study was supported by the National Institutes of Health. Partial
funding was provided to M.G.G. by the European Union doctoral fellowship
system through POSDRU Program 107/1.5/S/76841. The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 76
TC 8
Z9 8
U1 2
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 MAR 7
PY 2014
VL 9
IS 3
AR e91435
DI 10.1371/journal.pone.0091435
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC4IY
UT WOS:000332485800136
PM 24608965
ER
PT J
AU Bitan, M
He, WS
Zhang, MJ
Abdel-Azim, H
Ayas, MF
Bielorai, B
Carpenter, PA
Cairo, MS
Diaz, MA
Horan, JT
Jodele, S
Kitko, CL
Schultz, KR
Kletzel, M
Kasow, KA
Lehmann, LE
Mehta, PA
Shah, N
Pulsipher, MA
Prestidge, T
Seber, A
Shenoy, S
Woolfrey, AE
Yu, LC
Davies, SM
AF Bitan, Menachem
He, Wensheng
Zhang, Mei-Jie
Abdel-Azim, Hisham
Ayas, Mouhab Fakhreddine
Bielorai, Bella
Carpenter, Paul A.
Cairo, Mitchell S.
Angel Diaz, Miguel
Horan, John T.
Jodele, Sonata
Kitko, Carrie L.
Schultz, Kirk R.
Kletzel, Morris
Kasow, Kimberly A.
Lehmann, Leslie E.
Mehta, Parinda A.
Shah, Nirali
Pulsipher, Michael A.
Prestidge, Tim
Seber, Adriana
Shenoy, Shalini
Woolfrey, Ann E.
Yu, Lolie C.
Davies, Stella M.
TI Transplantation for children with acute myeloid leukemia: a comparison
of outcomes with reduced intensity and myeloablative regimens
SO BLOOD
LA English
DT Article
ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; ALLOGENEIC
TRANSPLANTATION; CURRENT CONTROVERSIES; SURVIVAL; DISEASE; THERAPY;
FAILURE; RECEIVE; VIEW
AB The safety and efficacy of reduced-intensity conditioning (RIC) regimens for the treatment of pediatric acute myeloid leukemia is unknown. We compared the outcome of allogeneic hematopoietic cell transplantation in children with acute myeloid leukemia using RIC regimens with those receiving myeloablative-conditioning (MAC) regimens. A total of 180 patients were evaluated (39 with RIC and 141 with MAC regimens). Results of univariate and multivariate analysis showed no significant differences in the rates of acute and chronic graft-versus-host disease, leukemia-free, and overall survival between treatment groups. The 5-year probabilities of overall survival with RIC and MAC regimens were 45% and 48%, respectively (P = .99). Moreover, relapse rates were not higher with RIC compared with MAC regimens (39% vs 39%; P = .95), and recipients of MAC regimens were not at higher risk for transplant-related mortality compared with recipients of RIC regimens (16% vs 16%; P = .73). After carefully controlled analyses, we found that in this relatively modest study population, the data supported a role for RIC regimens for acute myeloid leukemia in children undergoing allogeneic hematopoietic cell transplantation. The data also provided justification for designing a carefully controlled randomized clinical trial that examines the efficacy of regimen intensity in this population.
C1 [Bitan, Menachem] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Dept Pediat Hematol Oncol, IL-69978 Tel Aviv, Israel.
[He, Wensheng] Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
[Zhang, Mei-Jie] Med Coll Wisconsin, Div Biostat, Milwaukee, WI 53226 USA.
[Zhang, Mei-Jie] Childrens Hosp Los Angeles, Div Hematol Oncol & Blood Marrow Transplant Res I, Los Angeles, CA USA.
[Abdel-Azim, Hisham] Univ So Calif, Dept Pediat, Keck Sch Med, Los Angeles, CA 90089 USA.
[Ayas, Mouhab Fakhreddine] King Faisal Specialist Hosp & Res Ctr, Dept Pediat Hematol Oncol, Riyadh 11211, Saudi Arabia.
[Bielorai, Bella] Chaim Sheba Med Ctr, Dept Pediat Hematol Oncol & BMT, IL-52621 Tel Hashomer, Israel.
[Carpenter, Paul A.; Woolfrey, Ann E.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA.
[Cairo, Mitchell S.] New York Med Coll, Dept Pediat, Valhalla, NY 10595 USA.
[Angel Diaz, Miguel] Hosp Nino Jesus, Unidad Trasplante Hematopoyet, Madrid, Spain.
[Horan, John T.] Childrens Healthcare Atlanta Egleston, Atlanta, GA USA.
[Jodele, Sonata; Mehta, Parinda A.; Davies, Stella M.] Cincinnati Childrens Hosp Med Ctr, Div Bone Marrow Transplantat & Immune Deficiency, Cincinnati, OH 45229 USA.
[Kitko, Carrie L.] Univ Michigan, Pediat & Communicable Dis Blood & Marrow Transpla, Ann Arbor, MI 48109 USA.
[Schultz, Kirk R.] British Columbia Childrens Hosp, Vancouver, BC, Canada.
[Kletzel, Morris] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL USA.
[Kasow, Kimberly A.] Univ North Carolina Hosp, Div Pediat Hematol Oncol, Chapel Hill, NC USA.
[Lehmann, Leslie E.] Dana Farber Canc Inst, Pediat Stem Cell Transplant Unit, Boston, MA 02115 USA.
[Shah, Nirali] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Pulsipher, Michael A.] Univ Utah, Primary Childrens Med Ctr, Div Hematol Hematol Malignancies, Huntsman Canc Inst, Salt Lake City, UT USA.
[Prestidge, Tim] Starship Childrens Hosp, Auckland, New Zealand.
[Seber, Adriana] Inst Oncol Pediat, Sao Paulo, Brazil.
[Shenoy, Shalini] Washington Univ, St Louis Childrens Hosp, Pediat Stem Cell Transplant Program, St Louis, MO 63110 USA.
[Yu, Lolie C.] Louisiana State Univ, Div Hematol Oncol, Childrens Hosp, New Orleans, LA USA.
RP Davies, SM (reprint author), Cincinnati Childrens Hosp Med Ctr, 3333 Burnet Ave,MLC 11027, Cincinnati, OH 45229 USA.
EM stella.davies@cchmc.org
FU Public Health Service grant from the National Cancer Institute
[U24-CA76518]; National Heart Lung and Blood Institute; National
Institute of Allergy and Infectious Diseases; Health Resources and
Services Administration [HHSH234200637051C]
FX This study was funded by Public Health Service grant (U24-CA76518) from
the National Cancer Institute, the National Heart Lung and Blood
Institute, the National Institute of Allergy and Infectious Diseases,
and the Health Resources and Services Administration
(HHSH234200637051C).
NR 24
TC 16
Z9 17
U1 0
U2 1
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD MAR 6
PY 2014
VL 123
IS 10
BP 1615
EP 1620
DI 10.1182/blood-2013-10-535716
PG 6
WC Hematology
SC Hematology
GA AH0XR
UT WOS:000335844600030
PM 24435046
ER
PT J
AU Gan, L
O'Hanlon, TP
Gordon, AS
Rider, LG
Miller, FW
Burbelo, PD
AF Gan, Lu
O'Hanlon, Terrance P.
Gordon, Aaron S.
Rider, Lisa G.
Miller, Frederick W.
Burbelo, Peter D.
TI Twins discordant for myositis and systemic lupus erythematosus show
markedly enriched autoantibodies in the affected twin supporting
environmental influences in pathogenesis
SO BMC MUSCULOSKELETAL DISORDERS
LA English
DT Article
ID AUTOIMMUNE-DISEASES; MONOZYGOTIC TWINS; JUVENILE DERMATOMYOSITIS;
MOLECULAR PATHWAYS; ANTI-INTERFERON; EXPRESSION; POLYMYOSITIS;
INFECTIONS; RELATIVES; PROFILES
AB Background: Studies of twin pairs discordant for autoimmune conditions provide a unique opportunity to explore contributing factors triggered by complex gene-environment interactions.
Methods: In this cross-sectional study, thirty-one monozygotic or dizygotic twin pairs discordant for myositis or systemic lupus erythematosus (SLE), along with matched healthy controls were evaluated for antibodies against a panel of 21 autoantigens.
Results: Autoantibody profiling revealed that 42% of the affected twins showed significant seropositivity against autoantigens in the panel. In many of these affected twins, but none of healthy controls, there were high levels of autoantibodies detected against two or more autoantigens commonly seen in systemic autoimmune diseases including Ro52, Ro60, RNP-70 K and/or RNP-A. In contrast, only 10% (3/31) of the unaffected twins showed seropositivity and these immunoreactivities were against single autoantigens not seen in systemic autoimmune diseases. While no significant differences in autoantibodies were detected between the affected or unaffected twins against thyroid peroxidase, transglutaminase and several cytokines, 23% of the affected twins with myositis showed autoantibodies against the gastric ATPase. Analysis of the monozygotic twins separately also revealed a higher frequencies of autoantibodies in the affected twins compared to the unaffected twins (P = 0.046). Lastly, clinical analysis of both the affected monozygotic and dizygotic twins revealed that the autoantibody seropositive affected twins had a greater global disease activity score compared to seronegative affected twins (P = 0.019).
Conclusion: The findings of significantly more autoantibodies in the affected twins with myositis and SLE compared to the unaffected twins are consistent with potential non-genetic factors playing a role in autoantibody production and pathogenesis of these autoimmune disorders.
C1 [Gan, Lu; O'Hanlon, Terrance P.; Rider, Lisa G.; Miller, Frederick W.] Natl Inst Environm Hlth Sci, Environm Autoimmun Grp, Bethesda, MD 20892 USA.
[Gordon, Aaron S.; Burbelo, Peter D.] Natl Inst Dent & Craniofacial Res, Dental Clin Res Core, NIH, Bethesda, MD USA.
RP Miller, FW (reprint author), Natl Inst Environm Hlth Sci, Environm Autoimmun Grp, Bethesda, MD 20892 USA.
EM millerf@mail.nih.gov; burbelop@nidcr.nih.gov
RI Gan, Lu/L-5395-2014;
OI Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593
FU Intramural Research Program of the NIH, Division of Intramural Research,
National Institute of Dental and Craniofacial Research; National
Institute of Environmental Health Sciences
FX This research was supported by the Intramural Research Program of the
NIH, Division of Intramural Research, National Institute of Dental and
Craniofacial Research and National Institute of Environmental Health
Sciences.
NR 47
TC 5
Z9 5
U1 0
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2474
J9 BMC MUSCULOSKEL DIS
JI BMC Musculoskelet. Disord.
PD MAR 6
PY 2014
VL 15
AR 67
DI 10.1186/1471-2474-15-67
PG 11
WC Orthopedics; Rheumatology
SC Orthopedics; Rheumatology
GA AG1LM
UT WOS:000335176800001
PM 24602337
ER
PT J
AU Zhou, Q
Yang, D
Ombrello, AK
Zavialov, AV
Toro, C
Zavialov, AV
Stone, DL
Chae, JJ
Rosenzweig, SD
Bishop, K
Barron, KS
Kuehn, HS
Hoffmann, P
Negro, A
Tsai, WXL
Cowen, EW
Pei, W
Milner, JD
Silvin, C
Heller, T
Chin, DT
Patronas, NJ
Barber, JS
Lee, CCR
Wood, GM
Ling, A
Kelly, SJ
Kleiner, DE
Mullikin, JC
Ganson, NJ
Kong, HH
Hambleton, S
Candotti, F
Quezado, MM
Calvo, KR
Alao, H
Barham, BK
Jones, A
Meschia, JF
Worrall, BB
Kasner, SE
Rich, SS
Goldbach-Mansky, R
Abinun, M
Chalom, E
Gotte, AC
Punaro, M
Pascual, V
Verbsky, JW
Torgerson, TR
Singer, NG
Gershon, TR
Ozen, S
Karadag, O
Fleisher, TA
Remmers, EF
Burgess, SM
Moir, SL
Gadina, M
Sood, R
Hershfield, MS
Boehm, M
Kastner, DL
Aksentijevich, I
AF Zhou, Qing
Yang, Dan
Ombrello, Amanda K.
Zavialov, Andrey V.
Toro, Camilo
Zavialov, Anton V.
Stone, Deborah L.
Chae, Jae Jin
Rosenzweig, Sergio D.
Bishop, Kevin
Barron, Karyl S.
Kuehn, Hye Sun
Hoffmann, Patrycja
Negro, Alejandra
Tsai, Wanxia L.
Cowen, Edward W.
Pei, Wuhong
Milner, Joshua D.
Silvin, Christopher
Heller, Theo
Chin, David T.
Patronas, Nicholas J.
Barber, John S.
Lee, Chyi-Chia R.
Wood, Geryl M.
Ling, Alexander
Kelly, Susan J.
Kleiner, David E.
Mullikin, James C.
Ganson, Nancy J.
Kong, Heidi H.
Hambleton, Sophie
Candotti, Fabio
Quezado, Martha M.
Calvo, Katherine R.
Alao, Hawwa
Barham, Beverly K.
Jones, Anne
Meschia, James F.
Worrall, Bradford B.
Kasner, Scott E.
Rich, Stephen S.
Goldbach-Mansky, Raphaela
Abinun, Mario
Chalom, Elizabeth
Gotte, Alisa C.
Punaro, Marilynn
Pascual, Virginia
Verbsky, James W.
Torgerson, Troy R.
Singer, Nora G.
Gershon, Timothy R.
Ozen, Seza
Karadag, Omer
Fleisher, Thomas A.
Remmers, Elaine F.
Burgess, Shawn M.
Moir, Susan L.
Gadina, Massimo
Sood, Raman
Hershfield, Michael S.
Boehm, Manfred
Kastner, Daniel L.
Aksentijevich, Ivona
TI Early- Onset Stroke and Vasculopathy Associated with Mutations in ADA2
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID AICARDI-GOUTIERES SYNDROME; GROWTH-FACTOR; DISEASE; ATHEROSCLEROSIS;
MACROPHAGES; MONOCYTES
AB BackgroundWe observed a syndrome of intermittent fevers, early-onset lacunar strokes and other neurovascular manifestations, livedoid rash, hepatosplenomegaly, and systemic vasculopathy in three unrelated patients. We suspected a genetic cause because the disorder presented in early childhood.
MethodsWe performed whole-exome sequencing in the initial three patients and their unaffected parents and candidate-gene sequencing in three patients with a similar phenotype, as well as two young siblings with polyarteritis nodosa and one patient with small-vessel vasculitis. Enzyme assays, immunoblotting, immunohistochemical testing, flow cytometry, and cytokine profiling were performed on samples from the patients. To study protein function, we used morpholino-mediated knockdowns in zebrafish and short hairpin RNA knockdowns in U937 cells cultured with human dermal endothelial cells.
ResultsAll nine patients carried recessively inherited mutations in CECR1 (cat eye syndrome chromosome region, candidate 1), encoding adenosine deaminase 2 (ADA2), that were predicted to be deleterious; these mutations were rare or absent in healthy controls. Six patients were compound heterozygous for eight CECR1 mutations, whereas the three patients with polyarteritis nodosa or small-vessel vasculitis were homozygous for the p.Gly47Arg mutation. Patients had a marked reduction in the levels of ADA2 and ADA2-specific enzyme activity in the blood. Skin, liver, and brain biopsies revealed vasculopathic changes characterized by compromised endothelial integrity, endothelial cellular activation, and inflammation. Knockdown of a zebrafish ADA2 homologue caused intracranial hemorrhages and neutropenia phenotypes that were prevented by coinjection with nonmutated (but not with mutated) human CECR1. Monocytes from patients induced damage in cocultured endothelial-cell layers.
ConclusionsLoss-of-function mutations in CECR1 were associated with a spectrum of vascular and inflammatory phenotypes, ranging from early-onset recurrent stroke to systemic vasculopathy or vasculitis. (Funded by the National Institutes of Health Intramural Research Programs and others.)
Adenosine deaminase 2 (ADA2) is an enzyme involved in purine metabolism and a growth factor that influences the development of endothelial cells and leukocytes. This study shows that defects in ADA2 cause recurrent fevers, vascular pathologic features, and mild immunodeficiency. Patients with autoinflammatory disease sometimes present with clinical findings that encompass multiple organ systems.(1) Three unrelated children presented to the National Institutes of Health (NIH) Clinical Center with intermittent fevers, recurrent lacunar strokes, elevated levels of acute-phase reactants, livedoid rash, hepatosplenomegaly, and hypogammaglobulinemia. Collectively, these findings do not easily fit with any of the known inherited autoinflammatory diseases. Hereditary or acquired vascular disorders can have protean manifestations yet be caused by mutations in a single gene. Diseases such as the Aicardi-Goutieres syndrome,(2),(3) polypoidal choroidal vasculopathy,(4) sickle cell anemia,(5) livedoid vasculopathy,(6) and the small-vessel vasculitides(7),(8) are examples of systemic ...
C1 [Zhou, Qing; Ombrello, Amanda K.; Toro, Camilo; Stone, Deborah L.; Chae, Jae Jin; Bishop, Kevin; Hoffmann, Patrycja; Pei, Wuhong; Silvin, Christopher; Chin, David T.; Wood, Geryl M.; Mullikin, James C.; Candotti, Fabio; Barham, Beverly K.; Jones, Anne; Remmers, Elaine F.; Burgess, Shawn M.; Sood, Raman; Kastner, Daniel L.; Aksentijevich, Ivona] NHGRI, Bethesda, MD 20892 USA.
[Yang, Dan; Negro, Alejandra; Boehm, Manfred] NHLBI, Bethesda, MD 20892 USA.
[Rosenzweig, Sergio D.; Barron, Karyl S.; Milner, Joshua D.; Barber, John S.; Moir, Susan L.] NIAID, Bethesda, MD 20892 USA.
[Kuehn, Hye Sun; Patronas, Nicholas J.; Ling, Alexander; Calvo, Katherine R.; Fleisher, Thomas A.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Tsai, Wanxia L.; Goldbach-Mansky, Raphaela; Gadina, Massimo] NIAMSD, Bethesda, MD 20892 USA.
[Cowen, Edward W.; Lee, Chyi-Chia R.; Kleiner, David E.; Kong, Heidi H.; Quezado, Martha M.] NCI, Bethesda, MD 20892 USA.
[Heller, Theo; Alao, Hawwa] NIDDK, Bethesda, MD 20892 USA.
[Zavialov, Andrey V.; Zavialov, Anton V.] Univ Turku, Turku, Finland.
[Kelly, Susan J.; Ganson, Nancy J.; Hershfield, Michael S.] Duke Univ Med Ctr, Durham, NC USA.
[Gershon, Timothy R.] Univ N Carolina Neurosci Ctr, Chapel Hill, NC USA.
[Hambleton, Sophie; Abinun, Mario] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England.
[Meschia, James F.] Mayo Clin Florida, Jacksonville, FL USA.
[Worrall, Bradford B.; Rich, Stephen S.] Univ Virginia, Charlottesville, VA USA.
[Kasner, Scott E.] Univ Penn, Philadelphia, PA 19104 USA.
[Chalom, Elizabeth] Barnabas Hlth, W Orange, NJ USA.
[Gotte, Alisa C.; Punaro, Marilynn] Texas Scottish Rite Hosp Crippled Children, Dallas, TX USA.
[Pascual, Virginia] Baylor Inst Immunol Res, Dallas, TX USA.
[Verbsky, James W.] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Torgerson, Troy R.] Univ Washington, Seattle, WA 98195 USA.
[Torgerson, Troy R.] Seattle Childrens Res Inst, Seattle, WA 98195 USA.
[Singer, Nora G.] Metro Hlth Med Ctr, Cleveland, OH USA.
[Singer, Nora G.] Case Western Reserve Univ, Sch Med, Cleveland, OH USA.
[Ozen, Seza; Karadag, Omer] Hacettepe Univ, Fac Med, TR-06100 Ankara, Turkey.
RP Aksentijevich, I (reprint author), NHGRI, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM askentii@exchange.nih.gov; askentii@exchange.nih.gov
RI Zavialov, Anton/C-7664-2015; Yu, Xiaomin/I-6407-2016;
OI Zavialov, Anton/0000-0001-6191-5931; Singer, Nora/0000-0001-7041-723X;
Calvo, Katherine/0000-0002-0771-4191; Kong, Heidi/0000-0003-4424-064X;
Gershon, Timothy/0000-0001-7034-6400
FU National Institutes of Health (NIH) Intramural Research Programs;
National Human Genome Research Institute; National Institute of
Arthritis and Musculoskeletal and Skin Diseases; National Heart, Lung,
and Blood Institute (NHLBI); National Institute of Allergy and
Infectious Diseases; National Institute of Diabetes and Digestive and
Kidney Diseases; National Cancer Institute; Undiagnosed Diseases Program
of the Common Fund of the Office of the Director of the NIH; NIH
Clinical Center; Sigma Tau Pharmaceuticals; Finnish Academy
FX Supported by the National Institutes of Health (NIH) Intramural Research
Programs, including the Intramural Research Programs of the National
Human Genome Research Institute, the National Institute of Arthritis and
Musculoskeletal and Skin Diseases, the National Heart, Lung, and Blood
Institute (NHLBI), the National Institute of Allergy and Infectious
Diseases, the National Institute of Diabetes and Digestive and Kidney
Diseases, the National Cancer Institute, the Undiagnosed Diseases
Program of the Common Fund of the Office of the Director of the NIH, and
the NIH Clinical Center; and by grants from Sigma Tau Pharmaceuticals
(to Dr. Hershfield) and the Finnish Academy (to Drs. Andrey and Anton
Zavialov).
NR 25
TC 96
Z9 99
U1 6
U2 25
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAR 6
PY 2014
VL 370
IS 10
BP 911
EP 920
DI 10.1056/NEJMoa1307361
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA AC2EB
UT WOS:000332309800008
PM 24552284
ER
PT J
AU Bayro, MJ
Chen, B
Yau, WM
Tycko, R
AF Bayro, Marvin J.
Chen, Bo
Yau, Wai-Ming
Tycko, Robert
TI Site-Specific Structural Variations Accompanying Tubular Assembly of the
HIV-1 Capsid Protein
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE human immunodeficiency virus; AIDS; solid-state NMR; electron
microscopy; automated resonance assignment
ID SOLID-STATE NMR; NUCLEAR-MAGNETIC-RESONANCE; TERMINAL DIMERIZATION
DOMAIN; ANGLE-SPINNING NMR; 3-DIMENSIONAL STRUCTURE;
MOLECULAR-STRUCTURE; CRYSTAL-STRUCTURE; AMYLOID FIBRILS; TORSION ANGLES;
CYCLOPHILIN-A
AB The 231-residue capsid (CA) protein of human immunodeficiency virus type 1 (HIV-1) spontaneously self-assembles into tubes with a hexagonal lattice that is believed to mimic the surface lattice of conical capsid cores within intact virions. We report the results of solid-state nuclear magnetic resonance (NMR) measurements on HIV-1 CA tubes that provide new information regarding changes in molecular structure that accompany CA self-assembly, local dynamics within CA tubes, and possible mechanisms for the generation of lattice curvature. This information is contained in site-specific assignments of signals in two- and three-dimensional solid-state NMR spectra, conformation-dependent N-15 and C-13 NMR chemical shifts, detection of highly dynamic residues under solution NMR conditions, measurements of local variations in transverse spin relaxation rates of amide H-1 nuclei, and quantitative measurements of site-specific N-15-N-15 dipole dipole couplings. Our data show that most of the CA sequence is conformationally ordered and relatively rigid in tubular assemblies and that structures of the N-terminal domain (NTD) and the C-terminal domain (CTD) observed in solution are largely retained. However, specific segments, including the N-terminal 13-hairpin, the cyclophilin A binding loop, the inter-domain linker, segments involved in intermolecular NTD CTD interactions, and the C-terminal tail, have substantial static or dynamical disorder in tubular assemblies. Other segments, including the 310-helical segment in CTD, undergo clear conformational changes. Structural variations associated with curvature of the CA lattice appear to be localized in the inter-domain linker and intermolecular NTD CTD interface, while structural variations within NTD hexamers, around local 3-fold symmetry axes, and in CTD CTD dimerization interfaces are less significant. Published by Elsevier Ltd.
C1 [Bayro, Marvin J.; Yau, Wai-Ming; Tycko, Robert] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Chen, Bo] Univ Cent Florida, Dept Phys, Orlando, FL 32816 USA.
RP Tycko, R (reprint author), NIH, Bldg 5,Room 112, Bethesda, MD 20892 USA.
EM robertty@mail.nih.gov
RI Chen, Bo/F-3573-2015; Bayro, Marvin/Q-4643-2016
OI Bayro, Marvin/0000-0003-1482-9381
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases, a component of the National Institutes of
Health; National Institutes of Health Intramural AIDS Targeted Antiviral
Program; Air Force Office of Scientific Research [FA955013-1-0150];
National Institutes of Health [EB-002026]
FX This work was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases, a
component of the National Institutes of Health, and by the National
Institutes of Health Intramural AIDS Targeted Antiviral Program. M.J.B.
acknowledges postdoctoral support by the Intramural AIDS Research
Fellowship Program. B.C. acknowledges support from the Air Force Office
of Scientific Research, award number FA955013-1-0150. NMR spectra at
21.1 T were acquired at the Massachusetts Institute of
Technology/Harvard Center for Magnetic Resonance, supported by National
Institutes of Health grant EB-002026. We thank Lalit Deshmukh and
Guillermo Bermejo for helpful discussions regarding solution NMR
spectroscopy of CA and Xplor-NIH calculations, respectively.
NR 61
TC 21
Z9 21
U1 2
U2 35
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
EI 1089-8638
J9 J MOL BIOL
JI J. Mol. Biol.
PD MAR 6
PY 2014
VL 426
IS 5
SI SI
BP 1109
EP 1127
DI 10.1016/j.jmb.2013.12.021
PG 19
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AD0FG
UT WOS:000332909300010
PM 24370930
ER
PT J
AU Zhang, FQ
Wang, GQ
Shugart, YY
Xu, Y
Liu, CX
Wang, LF
Lu, TL
Yan, H
Ruan, YY
Chang, ZH
Tian, L
Jin, CH
Yuan, JM
Wang, ZQ
Zhu, W
Cao, LM
Liu, YS
Yue, WH
Zhang, D
AF Zhang, Fuquan
Wang, Guoqiang
Shugart, Yin Yao
Xu, Yong
Liu, Chenxing
Wang, Lifang
Lu, Tianlan
Yan, Hao
Ruan, Yanyan
Chang, Zaohuo
Tian, Lin
Jin, Chunhui
Yuan, Janmin
Wang, Zhiqiang
Zhu, Wei
Cao, Leiming
Liu, Yansong
Yue, Weihua
Zhang, Dai
TI Association analysis of a functional variant in ATXN2 with schizophrenia
SO NEUROSCIENCE LETTERS
LA English
DT Article
DE Schizophrenia; ATXN2; rs7969300
ID POLYGLUTAMINE EXPANSIONS; ATAXIN-2; PROTEIN; REPEAT; RISK; MICE
AB Schizophrenia (SZ) is a severe mental disorder characterized by multiple neurodevelopmental dysfunctions including a breakdown of thinking process and a deficit of typical emotional responses. Ataxin-2 (ATXN2) plays vital roles in cell proliferation and growth, and functional mutations of ATXN2 cause neurodegenerative phenotypes, including spinocerebellar ataxia type 2 (SCA2) and amyotrophic lateral sclerosis (ALS). To explore the possible role of ATXN2 in SZ, we conducted a two-stage study to examine the association of ATXN2 polymorphisms with SZ in the Han Chinese population. Association analysis of seven SNPs in 768 patients and 1348 controls revealed two associated SNPs, including rs630511 (P= 1.76E-4) and rs7969300 (P= 5.08E-4). We examined these two SNPs in a validation sample of 1957 patients and 1509 controls, and observed an association of rs7969300 with SZ (P=5.03E-3). The SNP rs7969300 is a non-synonymous SNP causing a Ser to Asn substitution, which is predicted to increase the protein stability of ATXN2. Our data suggest that the ATXN2 gene may confer vulnerability for SZ, adding further evidence for the genetic variants within the developmental pathway in the illness. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
C1 [Zhang, Fuquan; Wang, Guoqiang; Chang, Zaohuo; Tian, Lin; Jin, Chunhui; Yuan, Janmin; Wang, Zhiqiang; Zhu, Wei; Cao, Leiming; Liu, Yansong] Wuxi Mental Hlth Ctr, Wuxi, Jiangsu, Peoples R China.
[Zhang, Fuquan; Liu, Chenxing; Wang, Lifang; Lu, Tianlan; Yan, Hao; Ruan, Yanyan; Yue, Weihua; Zhang, Dai] Peking Univ, Inst Mental Hlth, Beijing 100191, Peoples R China.
[Zhang, Fuquan; Liu, Chenxing; Wang, Lifang; Lu, Tianlan; Yan, Hao; Ruan, Yanyan; Yue, Weihua; Zhang, Dai] Minist Hlth, Key Lab Mental Hlth, Beijing, Peoples R China.
[Shugart, Yin Yao] NIMH, Unit Stat Genom, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Xu, Yong] Shanxi Med Univ, Hosp 1, Dept Psychiat, Taiyuan, Peoples R China.
RP Yue, WH (reprint author), Peking Univ, Inst Mental Hlth, 51 Hua Yuan Bei Rd, Beijing 100191, Peoples R China.
EM dyue@bjmu.edu.cn; daizhang@bjmu.edu.cn
FU National High-Tech Research and Development Program of China
[2009AA022702]; National Natural Science Foundation of China [81000578,
81071087, 81071088]; National Basic Research Program of China
[2011CB707805]; International Science & Technology Cooperation Program
of China [2010DFB30820]; Intramural Research Program of NIMH, NIH, USA
FX We would sincerely thank the schizophrenia participants, their families
and the healthy volunteers for their participation, and all the medical
staff involved in specimen collection. The views expressed in this
presentation do not necessarily represent the views of the NIMH, NIH,
HHS, or the United States Government. This work was supported by
research grants from the National High-Tech Research and Development
Program of China (2009AA022702), the National Natural Science Foundation
of China (81000578, 81071087 and 81071088), the National Basic Research
Program of China (2011CB707805) and the International Science &
Technology Cooperation Program of China (2010DFB30820). YYS is supported
by the Intramural Research Program of NIMH, NIH, USA.
NR 25
TC 3
Z9 3
U1 0
U2 2
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3940
EI 1872-7972
J9 NEUROSCI LETT
JI Neurosci. Lett.
PD MAR 6
PY 2014
VL 562
BP 24
EP 27
DI 10.1016/j.neulet.2013.12.001
PG 4
WC Neurosciences
SC Neurosciences & Neurology
GA AD0FM
UT WOS:000332909900005
PM 24333172
ER
PT J
AU Tragante, V
Barnes, MR
Ganesh, SK
Lanktree, MB
Guo, W
Franceschini, N
Smith, EN
Johnson, T
Holmes, MV
Padmanabhan, S
Karczewski, KJ
Almoguera, B
Barnard, J
Baumert, J
Chang, YPC
Elbers, CC
Farrall, M
Fischer, ME
Gaunt, TR
Gho, JMIH
Gieger, C
Goel, A
Gong, Y
Isaacs, A
Kleber, ME
Leach, IM
McDonough, CW
Meijs, MFL
Melander, O
Nelson, CP
Nolte, IM
Pankratz, N
Price, TS
Shaffer, J
Shah, S
Tomaszewski, M
van der Most, PJ
Van Iperen, EPA
Vonk, JM
Witkowska, K
Wong, COL
Zhang, L
Beitelshees, AL
Berenson, GS
Bhatt, DL
Brown, M
Burt, A
Cooper-DeHoff, RM
Connell, JM
Cruickshanks, KJ
Curtis, SP
Davey-Smith, G
Delles, C
Gansevoort, RT
Guo, XQ
Haiqing, S
Hastie, CE
Hofker, MH
Hovingh, GK
Kim, DS
Kirkland, SA
Klein, BE
Klein, R
Li, YR
Maiwald, S
Newton-Cheh, C
O'Brien, ET
Onland-Moret, NC
Palmas, W
Parsa, A
Penninx, BW
Pettinger, M
Vasan, RS
Ranchalis, JE
Ridker, PM
Rose, LM
Sever, P
Shimbo, D
Steele, L
Stolk, RP
Thorand, B
Trip, MD
van Duijn, CM
Verschuren, WM
Wijmenga, C
Wyatt, S
Young, JH
Zwinderman, AH
Bezzina, CR
Boerwinkle, E
Casas, JP
Caulfield, MJ
Chakravarti, A
Chasman, DI
Davidson, KW
Doevendans, PA
Dominiczak, AF
FitzGerald, GA
Gums, JG
Fornage, M
Hakonarson, H
Halder, I
Hillege, HL
Illig, T
Jarvik, GP
Johnson, JA
Kastelein, JJP
Koenig, W
Kumari, M
Marz, W
Murray, SS
O'Connell, JR
Oldehinkel, AJ
Pankow, JS
Rader, DJ
Redline, S
Reilly, MP
Schadt, EE
Kottke-Marchant, K
Snieder, H
Snyder, M
Stanton, AV
Tobin, MD
Uitterlinden, AG
van der Harst, P
van der Schouw, YT
Samani, NJ
Watkins, H
Johnson, AD
Reiner, AP
Zhu, XF
de Bakker, PIW
Levy, D
Asselbergs, FW
Munroe, PB
Keating, BJ
AF Tragante, Vinicius
Barnes, Michael R.
Ganesh, Santhi K.
Lanktree, Matthew B.
Guo, Wei
Franceschini, Nora
Smith, Erin N.
Johnson, Toby
Holmes, Michael V.
Padmanabhan, Sandosh
Karczewski, Konrad J.
Almoguera, Berta
Barnard, John
Baumert, Jens
Chang, Yen-Pei Christy
Elbers, Clara C.
Farrall, Martin
Fischer, Mary E.
Gaunt, Tom R.
Gho, Johannes M. I. H.
Gieger, Christian
Goel, Anuj
Gong, Yan
Isaacs, Aaron
Kleber, Marcus E.
Leach, Irene Mateo
McDonough, Caitrin W.
Meijs, Matthijs F. L.
Melander, Olle
Nelson, Christopher P.
Nolte, Ilja M.
Pankratz, Nathan
Price, Tom S.
Shaffer, Jonathan
Shah, Sonia
Tomaszewski, Maciej
van der Most, Peter J.
Van Iperen, Erik P. A.
Vonk, Judith M.
Witkowska, Kate
Wong, Caroline O. L.
Zhang, Li
Beitelshees, Amber L.
Berenson, Gerald S.
Bhatt, Deepak L.
Brown, Morris
Burt, Amber
Cooper-DeHoff, Rhonda M.
Connell, John M.
Cruickshanks, Karen J.
Curtis, Sean P.
Davey-Smith, George
Delles, Christian
Gansevoort, Ron T.
Guo, Xiuqing
Haiqing, Shen
Hastie, Claire E.
Hofker, Marten H.
Hovingh, G. Kees
Kim, Daniel S.
Kirkland, Susan A.
Klein, Barbara E.
Klein, Ronald
Li, Yun R.
Maiwald, Steffi
Newton-Cheh, Christopher
O'Brien, Eoin T.
Onland-Moret, N. Charlotte
Palmas, Walter
Parsa, Afshin
Penninx, Brenda W.
Pettinger, Mary
Vasan, Ramachandran S.
Ranchalis, Jane E.
Ridker, Paul M.
Rose, Lynda M.
Sever, Peter
Shimbo, Daichi
Steele, Laura
Stolk, Ronald P.
Thorand, Barbara
Trip, Mieke D.
van Duijn, Cornelia M.
Verschuren, W. Monique
Wijmenga, Cisca
Wyatt, Sharon
Young, J. Hunter
Zwinderman, Aeilko H.
Bezzina, Connie R.
Boerwinkle, Eric
Casas, Juan P.
Caulfield, Mark J.
Chakravarti, Aravinda
Chasman, Daniel I.
Davidson, Karina W.
Doevendans, Pieter A.
Dominiczak, Anna F.
FitzGerald, Garret A.
Gums, John G.
Fornage, Myriam
Hakonarson, Hakon
Halder, Indrani
Hillege, Hans L.
Illig, Thomas
Jarvik, Gail P.
Johnson, Julie A.
Kastelein, John J. P.
Koenig, Wolfgang
Kumari, Meena
Maerz, Winfried
Murray, Sarah S.
O'Connell, Jeffery R.
Oldehinkel, Albertine J.
Pankow, James S.
Rader, Daniel J.
Redline, Susan
Reilly, Muredach P.
Schadt, Eric E.
Kottke-Marchant, Kandice
Snieder, Harold
Snyder, Michael
Stanton, Alice V.
Tobin, Martin D.
Uitterlinden, Andre G.
van der Harst, Pim
van der Schouw, Yvonne T.
Samani, Nilesh J.
Watkins, Hugh
Johnson, Andrew D.
Reiner, Alex P.
Zhu, Xiaofeng
de Bakker, Paul I. W.
Levy, Daniel
Asselbergs, Folkert W.
Munroe, Patricia B.
Keating, Brendan J.
TI Gene-centric Meta-analysis in 87,736 Individuals of European Ancestry
Identifies Multiple Blood-Pressure-Related Loci
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; CORONARY-ARTERY-DISEASE; HUMAN PREFRONTAL
CORTEX; FACTOR-KAPPA-B; ESSENTIAL-HYPERTENSION; SUSCEPTIBILITY LOCUS;
CANDIDATE GENES; COMMON VARIANTS; DRUG DISCOVERY; PULSE PRESSURE
AB Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped similar to 50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of European ancestry. Our analyses identified 11 previously undescribed associations in independent loci containing 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2, VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1, and NFAT5 at the Bonferroni-corrected array-wide significance threshold (p < 6 x 10(-7)) and confirmed 27 previously reported associations. Bioinformatic analysis of the 11 loci provided support for a putative role in hypertension of several genes, such as CDK6 and NUCB2. Analysis of potential pharmacological targets in databases of small molecules showed that ten of the genes are predicted to be a target for small molecules. In summary, we identified previously unknown loci associated with BP. Our findings extend our understanding of genes involved in BP regulation, which may provide new targets for therapeutic intervention or drug response stratification.
C1 [Tragante, Vinicius; Gho, Johannes M. I. H.; Meijs, Matthijs F. L.; Doevendans, Pieter A.; Asselbergs, Folkert W.] Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, NL-3584 CX Utrecht, Netherlands.
[Tragante, Vinicius; Elbers, Clara C.; de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Dept Med Genet, NL-3584 CX Utrecht, Netherlands.
[Barnes, Michael R.] Queen Mary Univ London, Barts & London Sch Med, William Harvey Res Inst, Inst Hlth Biomed Res Unit, London EC1M 6BQ, England.
[Ganesh, Santhi K.] Univ Michigan Hlth Syst, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA.
[Ganesh, Santhi K.] Univ Michigan Hlth Syst, Dept Human Genet, Div Cardiovasc Med, Ann Arbor, MI 48109 USA.
[Lanktree, Matthew B.] McMaster Univ, Dept Med, Hamilton, ON L8S 4L8, Canada.
[Guo, Wei; Zhu, Xiaofeng] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA.
[Franceschini, Nora] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA.
[Smith, Erin N.] Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA.
[Smith, Erin N.] Univ Calif San Diego, Radys Childrens Hosp, La Jolla, CA 92093 USA.
[Johnson, Toby; Witkowska, Kate; Wong, Caroline O. L.; Caulfield, Mark J.; Munroe, Patricia B.] Queen Mary Univ London, London EC1M 6BQ, England.
[Johnson, Toby; Witkowska, Kate; Wong, Caroline O. L.; Caulfield, Mark J.; Munroe, Patricia B.] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, Barts & London Genome Ctr, London EC1M 6BQ, England.
[Holmes, Michael V.; Steele, Laura; Keating, Brendan J.] Univ Penn, Dept Surg, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Padmanabhan, Sandosh; Dominiczak, Anna F.] Univ Glasgow, BHF, Glasgow Cardiovasc Res Ctr, Glasgow G12 8TA, Lanark, Scotland.
[Karczewski, Konrad J.; Snyder, Michael] Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA.
[Almoguera, Berta; Li, Yun R.; Keating, Brendan J.] Childrens Hosp Philadelphia, Abramson Res Ctr, Ctr Appl Genom, Philadelphia, PA 19104 USA.
[Barnard, John; Zhang, Li] Cleveland Clin, Lerner Res Inst, Dept Quantitat Hlth Sci, Cleveland, OH 44195 USA.
[Baumert, Jens; Thorand, Barbara] Helmholtz Zentrum Mu nchen, German Res Ctr Environm Hlth, Inst Epidemiol2, D-85764 Neuherberg, Germany.
[Chang, Yen-Pei Christy] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
[Chang, Yen-Pei Christy] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Elbers, Clara C.; Hofker, Marten H.; Onland-Moret, N. Charlotte; van der Schouw, Yvonne T.; de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, NL-3584 CX Utrecht, Netherlands.
[Farrall, Martin; Goel, Anuj; Watkins, Hugh] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
[Farrall, Martin; Goel, Anuj; Watkins, Hugh] Univ Oxford, Radcliffe Dept Med, Div Cardiovasc Med, Oxford OX3 9DU, England.
[Fischer, Mary E.; Cruickshanks, Karen J.; Klein, Barbara E.; Klein, Ronald] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI 53726 USA.
[Gaunt, Tom R.; Davey-Smith, George] Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England.
[Gieger, Christian] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Genet Epidemiol, D-85764 Neuherberg, Germany.
[Gong, Yan; McDonough, Caitrin W.; Cooper-DeHoff, Rhonda M.; Johnson, Julie A.] Univ Florida, Dept Pharmacotherapy & Translat Res, Gainesville, FL 32610 USA.
[Gong, Yan; McDonough, Caitrin W.; Cooper-DeHoff, Rhonda M.; Johnson, Julie A.] Univ Florida, Ctr Pharmacogenom, Gainesville, FL 32610 USA.
[Isaacs, Aaron; van Duijn, Cornelia M.] Erasmus MC, Dept Epidemiol, Genet Epidemiol Unit, NL-3015 GE Rotterdam, Netherlands.
[Kleber, Marcus E.; Jarvik, Gail P.; Maerz, Winfried] Heidelberg Univ, Med Fac Mannheim, Med Clin 5, D-68167 Mannheim, Germany.
[Leach, Irene Mateo; van der Harst, Pim] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9700 RB Groningen, Netherlands.
[Melander, Olle] Lund Univ, Dept Clin Sci, S-20502 Malmo, Sweden.
[Melander, Olle] Skane Univ Hosp, Ctr Emergency Med, S-20502 Malmo, Sweden.
[Nelson, Christopher P.; Tomaszewski, Maciej; Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, Leicester LE3 9QP, Leics, England.
[Nelson, Christopher P.; Samani, Nilesh J.] Glenfield Hosp, NIHR, Lecister Cardiovasc Biomed Res Unit, Leicester LE3 9QP, Leics, England.
[Nolte, Ilja M.; van der Most, Peter J.; Vonk, Judith M.; Snieder, Harold] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, NL-9700 RB Groningen, Netherlands.
[Pankratz, Nathan] Univ Minnesota, Dept Lab Med & Pathol, Inst Human Genet, Minneapolis, MN 55455 USA.
[Price, Tom S.] Inst Psychiat, MRC, SGDP Ctr, London SE5 8AF, England.
[Shaffer, Jonathan; Shimbo, Daichi] Columbia Univ, Dept Med, New York, NY 10032 USA.
[Shah, Sonia] UCL, Genet Inst, Dept Genet Evolut & Environm, London WC1E 6BT, England.
[Van Iperen, Erik P. A.; van der Harst, Pim; Asselbergs, Folkert W.] ICIN, Durrer Ctr Cardiogenet Res, Netherlands Heart Inst, NL-3511 GC Utrecht, Netherlands.
[Van Iperen, Erik P. A.; Zwinderman, Aeilko H.] Univ Amsterdam, Acad Med Ctr, Dept Clin Epidemiol Biostat & Bioinformat, NL-1105 AZ Amsterdam, Netherlands.
[Beitelshees, Amber L.; Haiqing, Shen; Parsa, Afshin] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.
[Berenson, Gerald S.] Tulane Univ, Dept Epidemiol, New Orleans, LA 70118 USA.
[Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Brown, Morris] Univ Cambridge, Addenbrookes Hosp, Clin Pharmacol Unit, Cambridge CB2 2QQ, England.
[Burt, Amber; Ranchalis, Jane E.] Univ Washington, Dept Med Med Genet, Seattle, WA 98195 USA.
[Connell, John M.] Univ Dundee, Ninewells Hosp & Med Sch, Dundee DD1 9SY, Scotland.
[Cruickshanks, Karen J.] Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI 53726 USA.
[Curtis, Sean P.] Merck Res Labs, Rahway, NJ 07065 USA.
[Delles, Christian; Hastie, Claire E.] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow G12 8TA, Lanark, Scotland.
[Gansevoort, Ron T.] Univ Groningen, Univ Med Ctr Groningen, Dept Med, Div Nephrol, NL-9700 RB Groningen, Netherlands.
[Guo, Xiuqing] Cedars Sinai Med Ctr, PEDS, Los Angeles, CA 90048 USA.
[Hofker, Marten H.] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol & Med Biol, Med Biol Div, NL-9700 RB Groningen, Netherlands.
[Hovingh, G. Kees; Maiwald, Steffi; Kastelein, John J. P.] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands.
[Kim, Daniel S.] Univ Washington, Dept Med Med Genet, Seattle, WA 98195 USA.
[Kim, Daniel S.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
[Kirkland, Susan A.] Dalhousie Univ, Dept Community Hlth & Epidemiol, Halifax, NS B3H 1V7, Canada.
[Newton-Cheh, Christopher] Massachusetts Gen Hosp, Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.
[O'Brien, Eoin T.] Univ Coll Dublin, Conway Inst Biomol & Biomed Res, Dublin 4, Ireland.
[Penninx, Brenda W.] Vrije Univ Amsterdam, Med Ctr, EMGO Inst, Dept Psychiat, NL-1081 BT Amsterdam, Netherlands.
[Pettinger, Mary] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[Ridker, Paul M.; Rose, Lynda M.; Chasman, Daniel I.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA.
[Ridker, Paul M.; Chasman, Daniel I.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Sever, Peter] Univ London Imperial Coll Sci Technol & Med, Int Ctr Circulatory Hlth, London W2 1LA, England.
[Trip, Mieke D.] Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands.
[Verschuren, W. Monique] Natl Inst Publ Hlth & Environm, RIVM, NL-3720 BA Bilthoven, Netherlands.
[Wijmenga, Cisca] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands.
[Wyatt, Sharon] Univ Mississippi, Med Ctr, Sch Nursing, Jackson, MS 39216 USA.
[Wyatt, Sharon] Univ Mississippi, Med Ctr, Sch Med, Jackson, MS 39216 USA.
[Young, J. Hunter] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Bezzina, Connie R.] Univ Amsterdam, Acad Med Ctr, Heart Failure Res Ctr, Dept Clin & Expt Cardiol, NL-1105 AZ Amsterdam, Netherlands.
[Bezzina, Connie R.] Univ Amsterdam, Acad Med Ctr, Mol & Expt Cardiol Grp, NL-1105 AZ Amsterdam, Netherlands.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Div Epidemiol, Houston, TX 77030 USA.
[Casas, Juan P.] London Sch Hyg & Trop Med, Fac Epidemiol & Populat Hlth, London WC1E 7HT, England.
[Casas, Juan P.] UCL, Dept Epidemiol & Publ Hlth, Genet Epidemiol Grp, London WC1E 6BT, England.
[Chakravarti, Aravinda] Johns Hopkins Univ, Sch Med, Ctr Complex Dis Genom, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA.
[Davidson, Karina W.] Columbia Univ, Dept Med, New York, NY 10032 USA.
[Davidson, Karina W.] Columbia Univ, Dept Psychiat, New York, NY 10032 USA.
[FitzGerald, Garret A.] Univ Penn, Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA.
[Gums, John G.] Univ Florida, Dept Pharmacotherapy & Translat Res, Gainesville, FL 32610 USA.
[Gums, John G.] Univ Florida, Dept Community Hlth, Gainesville, FL 32610 USA.
[Gums, John G.] Univ Florida, Dept Family Med, Gainesville, FL 32610 USA.
[Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA.
[Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Div Epidemiol Human Genet & Environm Sci, Houston, TX 77030 USA.
[Halder, Indrani] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15261 USA.
[Illig, Thomas] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, D-85764 Neuherberg, Germany.
[Illig, Thomas] Hannover Med Sch, Hannover Unified Biobank, D-30625 Hannover, Germany.
[Koenig, Wolfgang] Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, D-89081 Ulm, Germany.
[Kumari, Meena] UCL, Dept Epidemiol & Publ Hlth, Div Populat Hlth, London WC1E 7HB, England.
[Jarvik, Gail P.] Synlab Serv GmbH, Synlab Acad, D-69214 Mannheim, Germany.
[Maerz, Winfried] Med Univ Graz, Inst Clin Med, A-8036 Graz, Austria.
[Maerz, Winfried] Med Univ Graz, Chem Lab Diagnost, A-8036 Graz, Austria.
[Murray, Sarah S.] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92037 USA.
[Oldehinkel, Albertine J.] Univ Groningen, Univ Med Ctr Groningen, Interdisciplinary Ctr Psychopathol & Emot Regulat, NL-9700 RB Groningen, Netherlands.
[Pankow, James S.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN 55454 USA.
[Rader, Daniel J.; Reilly, Muredach P.] Univ Penn, Perelman Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA.
[Redline, Susan] Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA 02115 USA.
[Schadt, Eric E.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA.
[Kottke-Marchant, Kandice] Cleveland Clin, Pathol & Lab Med Inst, Cleveland, OH 44195 USA.
[Stanton, Alice V.] Royal Coll Surgeons Ireland, Dublin 2, Ireland.
[Tobin, Martin D.] Univ Leicester, Dept Hlth Sci, Leicester LE1 7RH, Leics, England.
[Uitterlinden, Andre G.] Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.
[Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.
[Johnson, Andrew D.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[de Bakker, Paul I. W.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet, Boston, MA 02115 USA.
[de Bakker, Paul I. W.] Broad Inst MIT & Harvard, Cambridge, MA USA.
[Levy, Daniel] NHLBI, Ctr Populat Studies, Framingham, MA 01702 USA.
[Asselbergs, Folkert W.] UCL, Fac Populat Hlth Sci, Inst Cardiovasc Sci, London WC1E 6BT, England.
[Keating, Brendan J.] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA.
RP Munroe, PB (reprint author), Queen Mary Univ London, London EC1M 6BQ, England.
EM p.b.munroe@qmul.ac.uk; bkeating@mail.med.upenn.edu
RI Wijmenga, Cisca/D-2173-2009; de Bakker, Paul/B-8730-2009; Onland-Moret,
N. Charlotte/G-9185-2011; Thorand, Barbara/B-5349-2014; Johnson,
Andrew/G-6520-2013; Padmanabhan, Sandosh/S-3963-2016; van der Schouw,
Yvonne/F-8327-2014; Shah, Sonia/N-7547-2013; Price, Thomas/B-7372-2008;
Stanton, Alice/F-4697-2012; Jarvik, Gail/N-6476-2014; Gaunt,
Tom/O-3918-2014; Davey Smith, George/A-7407-2013;
OI de Bakker, Paul/0000-0001-7735-7858; Thorand,
Barbara/0000-0002-8416-6440; van der Schouw, Yvonne/0000-0002-4605-435X;
Shah, Sonia/0000-0001-5860-4526; Price, Thomas/0000-0001-7356-2109;
Jarvik, Gail/0000-0002-6710-8708; Gaunt, Tom/0000-0003-0924-3247; Davey
Smith, George/0000-0002-1407-8314; Stanton, Alice/0000-0002-4961-165X;
Wijmenga, Cisca/0000-0002-5635-1614; Johnson, Toby/0000-0002-5998-3270;
Karczewski, Konrad/0000-0003-2878-4671; Padmanabhan,
Sandosh/0000-0003-3869-5808; Ramachandran, Vasan/0000-0001-7357-5970;
Gieger, Christian/0000-0001-6986-9554; Watkins,
Hugh/0000-0002-5287-9016; Pankow, James/0000-0001-7076-483X; Kleber,
Marcus/0000-0003-0663-7275
FU British Heart Foundation [FS/11/35/28871, FS/12/33/29561, FS/12/8/29377,
FS/14/12/30540, PG/07/085/23349, PG/09/022/26739, SP/08/002/24118];
Medical Research Council [MR/K006584/1, G0802432, G0902313, G9521010,
MC_UU_12013/1, MC_UU_12013/8, MR/K013351/1]; NCATS NIH HHS [UL1
TR000064, UL1 TR000124]; NHLBI NIH HHS [R01 HL074730]; NIA NIH HHS [R01
AG016592, R01 AG021917, R37 AG011099]; NIDDK NIH HHS [P30 DK063491, P30
DK072488]; NIGMS NIH HHS [U01 GM074492]; Wellcome Trust [090532]
NR 114
TC 50
Z9 51
U1 3
U2 29
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
EI 1537-6605
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD MAR 6
PY 2014
VL 94
IS 3
BP 349
EP 360
DI 10.1016/j.ajhg.2013.12.016
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA AC6DK
UT WOS:000332611400009
PM 24560520
ER
PT J
AU Liu, MY
Chen, KQ
Yoshimura, T
Liu, Y
Gong, WH
Le, YY
Gao, JL
Zhao, JH
Wang, JM
Wang, AM
AF Liu, Mingyong
Chen, Keqiang
Yoshimura, Teizo
Liu, Ying
Gong, Wanghua
Le, Yingying
Gao, Ji-Liang
Zhao, Jianhua
Wang, Ji Ming
Wang, Aimin
TI Formylpeptide Receptors Mediate Rapid Neutrophil Mobilization to
Accelerate Wound Healing
SO PLOS ONE
LA English
DT Article
ID HOST-DEFENSE; GRO-ALPHA; IN-VIVO; MICE; INFLAMMATION; CHEMOKINES;
ACCUMULATION; RECRUITMENT; MIGRATION; CXCR1/2
AB Wound healing is a multi-phased pathophysiological process requiring chemoattractant receptor-dependent accumulation of myeloid cells in the lesion. Two G protein-coupled formylpeptide receptors Fpr1 and Fpr2 mediate rapid neutrophil infiltration in the liver of Listeria-infected mice by sensing pathogen-derived chemotactic ligands. These receptors also recognize host-derived chemotactic peptides in inflammation and injury. Here we report the capacity of Fprs to promote the healing of sterile skin wound in mice by initiating neutrophil infiltration. We found that in normal miceneutrophils rapidly infiltrated the dermis in the wound before the production of neutrophil-specific chemokines by the injured tissue. In contrast, rapid neutrophil infiltration was markedly reduced with delayed wound closure in mice deficient in both Fprs. In addition, we detected Fpr ligand activity that chemoattracted neutrophils into the wound tissue. Our study thus demonstrates that Fprs are critical for normal healing of the sterile skin wound by mediating the first wave of neutrophil infiltration.
C1 [Liu, Mingyong; Zhao, Jianhua] Third Mil Med Univ, Daping Hosp, Dept Spine Surg, Chongqing, Peoples R China.
[Liu, Mingyong; Chen, Keqiang; Yoshimura, Teizo; Liu, Ying; Wang, Ji Ming] NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21701 USA.
[Liu, Ying] Natl Ctr Nanosci & Technol, Beijing, Peoples R China.
[Gong, Wanghua] Sci Applicat Int Corp Frederick, Basic Res Program, Frederick, MD USA.
[Le, Yingying] Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Food Safety Res, Inst Nutr Sci, Shanghai, Peoples R China.
[Gao, Ji-Liang] NIAID, Lab Mol Immunol, Bethesda, MD 20892 USA.
[Wang, Aimin] Third Mil Med Univ, Ctr Orthoped, Daping Hosp, Chongqing, Peoples R China.
RP Liu, MY (reprint author), Third Mil Med Univ, Daping Hosp, Dept Spine Surg, Chongqing, Peoples R China.
EM mingyong_liu@163.com
OI Zhao, Jianhua/0000-0001-5758-3479
FU National Natural Science Foundation of China (NSFC) [81070981,
201111606]; National Cancer Institute (NCI), National Institutes of
Health (NIH) [HHSN261200800001E]; Intramural Research Program of the
NCI, NIH, United States of America
FX This project was supported in part by the National Natural Science
Foundation of China (NSFC, No. 81070981 and 201111606). This project was
also funded in part with Federal funds from the National Cancer
Institute (NCI), National Institutes of Health (NIH), under Contract No.
HHSN261200800001E and was supported in part by the Intramural Research
Program of the NCI, NIH, United States of America. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 28
TC 8
Z9 9
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 6
PY 2014
VL 9
IS 3
AR e90613
DI 10.1371/journal.pone.0090613
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC4ID
UT WOS:000332483600068
PM 24603667
ER
PT J
AU Wu, XY
Cai, H
Kallianpur, A
Li, HL
Yang, G
Gao, J
Xiang, YB
Ji, BT
Yu-Tang
Zheng, W
Shu, XO
AF Wu, Xiaoyan
Cai, Hui
Kallianpur, Asha
Li, Honglan
Yang, Gong
Gao, Jing
Xiang, Yong-Bing
Ji, Bu-Tian
Yu-Tang
Zheng, Wei
Shu, Xiao-Ou
TI Impact of Premature Ovarian Failure on Mortality and Morbidity among
Chinese Women
SO PLOS ONE
LA English
DT Article
ID ISCHEMIC-HEART-DISEASE; NATURAL MENOPAUSE; BREAST-CANCER; AGE; HEALTH;
ESTRONE; RISK; ANDROSTENEDIONE; REPRODUCIBILITY; QUESTIONNAIRE
AB Objective: To evaluate associations of premature ovarian failure (POF) with mortality and morbidity in Asian populations.
Methods: We identified 1,003 cases of POF among 36,402 postmenopausal women who participated in the Shanghai Women's Health Study, a population-based cohort study. Cox regression and logistic regression models were applied in data analysis.
Results: After adjustment for potential confounding factors, we found that POF increased the risk of total and cancer-specific mortality (HR (95% CIs): 1.29 (1.08-1.54) and 1.38 (1.05-1.81), respectively). POF was also associated with high prevalence of autoimmune disease (OR (95% CI): 1.56 (1.04-2.35)) but decreased incidence of breast cancer (OR (95% CI): 0.59 (0.38-0.91)). Similar results were observed when hormone replacement therapy users were excluded from the analysis. POF is associated with high waist-to-hip ratio.
Conclusions: Our results suggest that women with POF experience increased mortality and that these women may benefit from heightened surveillance and appropriate interventions.
C1 [Wu, Xiaoyan; Cai, Hui; Kallianpur, Asha; Yang, Gong; Zheng, Wei; Shu, Xiao-Ou] Vanderbilt Univ, Sch Med, Dept Med, Div Epidemiol, Nashville, TN 37212 USA.
[Wu, Xiaoyan; Cai, Hui; Kallianpur, Asha; Yang, Gong; Zheng, Wei; Shu, Xiao-Ou] Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
[Kallianpur, Asha] Vanderbilt Univ, Sch Med, Div Gen Internal Med & Publ Hlth, Dept Med, Nashville, TN 37212 USA.
[Li, Honglan; Gao, Jing; Xiang, Yong-Bing; Yu-Tang] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
[Ji, Bu-Tian] NCI, Occupat Epidemiol Branch, NIH, Bethesda, MD 20892 USA.
RP Shu, XO (reprint author), Vanderbilt Univ, Sch Med, Dept Med, Div Epidemiol, Nashville, TN 37212 USA.
EM Xiao-ou.shu@vanderbilt.edu
FU US National Institutes of Health (NHI) [R37 CA 070867, R01 HL079123]
FX Funding support for this work was provided by US National Institutes of
Health (NHI) grants R37 CA 070867 (PI: W Zheng) and R01 HL079123 (PI: XO
Shu). The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 40
TC 6
Z9 11
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 MAR 6
PY 2014
VL 9
IS 3
AR e89597
DI 10.1371/journal.pone.0089597
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC4ID
UT WOS:000332483600014
PM 24603759
ER
PT J
AU Wen, H
Gomella, AA
Patel, A
Wolfe, DE
Lynch, SK
Xiao, XH
Morgan, N
AF Wen, Han
Gomella, Andrew A.
Patel, Ajay
Wolfe, Douglas E.
Lynch, Susanna K.
Xiao, Xianghui
Morgan, Nicole
TI Boosting phase contrast with a grating Bonse-Hart interferometer of 200
nanometre grating period
SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY A-MATHEMATICAL PHYSICAL
AND ENGINEERING SCIENCES
LA English
DT Article
DE X-ray; grating; phase contrast; absolute phase; interferometer; compact
source
ID X-RAY SOURCES; FABRICATION
AB We report on a grating Bonse-Hart interferometer for phase-contrast imaging with hard X-rays. The method overcomes limitations in the level of sensitivity that can be achieved with the well-known Talbot grating interferometer, and without the stringent spectral filtering at any given incident angle imposed by the classic Bonse-Hart interferometer. The device operates in the far-field regime, where an incident beam is split by a diffraction grating into two widely separated beams, which are redirected by a second diffraction grating to merge at a third grating, where they coherently interfere. The wide separation of the interfering beams results in large phase contrast, and in some cases absolute phase images are obtained. Imaging experiments were performed using diffraction gratings of 200 nm period, at 22.5 keV and 1.5% spectral bandwidth on a bending-magnetic beamline. Novel design and fabrication process were used to achieve the small grating period. Using a slitted incident beam, we acquired absolute and differential phase images of lightly absorbing samples. An advantage of this method is that it uses only phase modulating gratings, which are easier to fabricate than absorption gratings of the same periods.
C1 [Wen, Han; Gomella, Andrew A.; Patel, Ajay; Lynch, Susanna K.; Morgan, Nicole] NHLBI, NIH, Bethesda, MD 20892 USA.
[Wolfe, Douglas E.] Penn State Univ, Dept Mat Sci & Engn, State Coll, PA USA.
[Xiao, Xianghui] Argonne Natl Lab, Adv Photon Source, Lemont, IL USA.
RP Wen, H (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM wenh@nhlbi.nih.gov
RI Wen, Han/G-3081-2010
OI Wen, Han/0000-0001-6844-2997
FU Division of Intramural Research, National Heart, Lung and Blood
Institute, National Institutes of Health [HL006143-01]; US Department of
Energy, Office of Science, Office of Basic Energy Sciences
[DE-AC02-06CH11357]
FX The work was funded by the Division of Intramural Research, National
Heart, Lung and Blood Institute, National Institutes of Health, under
project no. HL006143-01. Use of the Advanced Photon Source at Argonne
National Laboratory was supported by the US Department of Energy, Office
of Science, Office of Basic Energy Sciences, under contract no.
DE-AC02-06CH11357.
NR 21
TC 1
Z9 1
U1 2
U2 16
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 1364-503X
EI 1471-2962
J9 PHILOS T R SOC A
JI Philos. Trans. R. Soc. A-Math. Phys. Eng. Sci.
PD MAR 6
PY 2014
VL 372
IS 2010
AR 20130028
DI 10.1098/rsta.2013.0028
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC2XM
UT WOS:000332379600005
PM 24470412
ER
PT J
AU Tibes, R
Mesa, RA
AF Tibes, Raoul
Mesa, Ruben A.
TI Targeting hedgehog signaling in myelofibrosis and other hematologic
malignancies
SO JOURNAL OF HEMATOLOGY & ONCOLOGY
LA English
DT Review
DE Myelofibrosis; Targeted therapy; Hedgehog pathway inhibitors; Janus
kinase inhibitors
ID INTERNATIONAL WORKING GROUP; PROGNOSTIC SCORING SYSTEM; BASAL-CELL
CARCINOMA; TYROSINE KINASE JAK2; QUALITY-OF-LIFE; MURINE YOLK-SAC;
MYELOPROLIFERATIVE NEOPLASMS; MYELOID METAPLASIA; POLYCYTHEMIA-VERA;
STEM-CELLS
AB Treatment of myelofibrosis (MF), a BCR-ABL-negative myeloproliferative neoplasm, is challenging. The only current potentially curative option, allogeneic hematopoietic stem cell transplant, is recommended for few patients. The remaining patients are treated with palliative therapies to manage MF-related anemia and splenomegaly. Identification of a mutation in the Janus kinase 2 (JAK2) gene (JAK2 V617F) in more than half of all patients with MF has prompted the discovery and clinical development of inhibitors that target JAK2. Although treatment with JAK2 inhibitors has been shown to improve symptom response and quality of life in patients with MF, these drugs do not alter the underlying disease; therefore, novel therapies are needed. The hedgehog (Hh) signaling pathway has been shown to play a role in normal hematopoiesis and in the tumorigenesis of hematologic malignancies. Moreover, inhibitors of the Hh pathway have been shown to inhibit growth and self-renewal capacity in preclinical models of MF. In a mouse model of MF, combined inhibition of the Hh and JAK pathways reduced JAK2 mutant allele burden, reduced bone marrow fibrosis, and reduced white blood cell and platelet counts. Preliminary clinical data also suggest that inhibition of the Hh pathway, alone or in combination with JAK2 inhibition, may enable disease modification in patients with MF. Future studies, including one combining the Hh pathway inhibitor sonidegib and the JAK2 inhibitor ruxolitinib, are underway in patients with MF and will inform whether this combination approach can lead to true disease modification.
C1 [Tibes, Raoul; Mesa, Ruben A.] Mayo Clin, Ctr Canc, NCI Designated Comprehens Canc Ctr, Scottsdale, AZ 85259 USA.
RP Tibes, R (reprint author), Mayo Clin, Ctr Canc, NCI Designated Comprehens Canc Ctr, 13400 E Shea Blvd, Scottsdale, AZ 85259 USA.
EM tibes.raoul@mayo.edu
FU Novartis Pharmaceuticals Corporation
FX The authors thank Jillian Brechbiel, PhD, and Karen Miller-Moslin, PhD,
for medical editorial assistance with this manuscript. Financial support
for editorial assistance was provided by Novartis Pharmaceuticals
Corporation.
NR 110
TC 15
Z9 15
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1756-8722
J9 J HEMATOL ONCOL
JI J. Hematol. Oncol.
PD MAR 5
PY 2014
VL 7
AR 18
DI 10.1186/1756-8722-7-18
PG 12
WC Oncology; Hematology
SC Oncology; Hematology
GA AG2SF
UT WOS:000335265800001
PM 24598114
ER
PT J
AU Akarolo-Anthony, SN
Dal Maso, L
Igbinoba, F
Mbulaiteye, SM
Adebamowo, CA
AF Akarolo-Anthony, Sally N.
Dal Maso, Luigino
Igbinoba, Festus
Mbulaiteye, Sam M.
Adebamowo, Clement A.
TI Cancer burden among HIV-positive persons in Nigeria: preliminary
findings from the Nigerian AIDS-cancer match study
SO INFECTIOUS AGENTS AND CANCER
LA English
DT Article
DE HIV; Cancer; AIDS-cancer match; Registry linkage; Nigeria
ID IMMUNODEFICIENCY-VIRUS-INFECTION; KAPOSIS-SARCOMA; ANTIRETROVIRAL
THERAPY; SOUTH-AFRICA; SPECTRUM; UGANDA; EPIDEMIOLOGY; MALIGNANCIES;
REGISTRY; POPULATION
AB Background: Although Nigeria has a large HIV epidemic, the impact of HIV on cancer in Nigerians is unknown.
Methods: We conducted a registry linkage study using a probabilistic matching algorithm among a cohort of HIV positive persons registered at health facilities where the Institute of Human Virology Nigeria (IHVN) provides HIV prevention and treatment services. Their data was linked to data from 2009 to 2012 in the Abuja Cancer Registry. Match compatible files with first name, last name, sex, date of birth and unique HIV cohort identification numbers were provided by each registry and used for the linkage analysis. We describe demographic characteristics of the HIV clients and compute Standardized Incidence Ratios (SIRs) to evaluate the association of various cancers with HIV infection.
Results: Between 2005 and 2012, 17,826 persons living with HIV (PLWA) were registered at IHVN. Their median age (Interquartile range (IQR)) was 33 (27-40) years; 41% (7246/17826) were men and 59% (10580/17826) were women. From 2009 to 2012, 2,029 clients with invasive cancers were registered at the Abuja Cancer Registry. The median age (IQR) of the cancer clients was 45 (35-68) years. Among PLWA, 39 cancer cases were identified, 69% (27/39) were incident cancers and 31% (12/39) were prevalent cancers. The SIR (95% CI) for the AIDS Defining Cancers were 5.7 (4.1, 7.2) and 2.0 (0.4, 3.5), for Kaposi Sarcoma and Cervical Cancer respectively.
Conclusion: The risk of Kaposi Sarcoma but not Cervical Cancer or Non-Hodgkin's Lymphoma, was significantly increased among HIV positive persons, compared to the general population in Nigeria.
C1 [Akarolo-Anthony, Sally N.; Adebamowo, Clement A.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Akarolo-Anthony, Sally N.; Adebamowo, Clement A.] Inst Human Virol, Off Strateg Informat & Res, Abuja, Nigeria.
[Dal Maso, Luigino] IRCCS, Aviano Canc Ctr, Epidemiol & Biostat Unit, Aviano, Italy.
[Igbinoba, Festus] Natl Hosp Abuja, Abuja Canc Registry, Abuja, Nigeria.
[Mbulaiteye, Sam M.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Adebamowo, Clement A.] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA.
[Adebamowo, Clement A.] Univ Maryland, Sch Med, Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
RP Akarolo-Anthony, SN (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 677 Huntington Ave, Boston, MA 02115 USA.
EM sna094@mail.harvard.edu
OI Adebamowo, Sally/0000-0003-4713-2433; dal maso,
luigino/0000-0001-6163-200X
FU IHV-UM Capacity Development for Research into AIDS Associated
Malignancies (CADRE), a U.S. National Institutes of Health [NIH/NCI
D43CA153792-01]
FX We thank Serraino Diego for his contribution to the registry linkage
analysis. This research was supported by the IHV-UM Capacity Development
for Research into AIDS Associated Malignancies (CADRE), a U.S. National
Institutes of Health grant (NIH/NCI D43CA153792-01) awarded to CAA.
NR 35
TC 9
Z9 9
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1750-9378
J9 INFECT AGENTS CANCER
JI Infect. Agents Cancer
PD MAR 5
PY 2014
VL 9
AR 1
DI 10.1186/1750-9378-9-1
PG 7
WC Oncology; Immunology
SC Oncology; Immunology
GA AD3SC
UT WOS:000333165300001
PM 24597902
ER
PT J
AU Moreno, E
Moreno-Delgado, D
Navarro, G
Hoffmann, HM
Fuentes, S
Rosell-Vilar, S
Gasperini, P
Rodriguez-Ruiz, M
Medrano, M
Mallol, J
Cortes, A
Casado, V
Lluis, C
Ferre, S
Ortiz, J
Canela, E
McCormick, PJ
AF Moreno, Estefania
Moreno-Delgado, David
Navarro, Gemma
Hoffmann, Hanne M.
Fuentes, Silvia
Rosell-Vilar, Santi
Gasperini, Paola
Rodriguez-Ruiz, Mar
Medrano, Mireia
Mallol, Josefa
Cortes, Antoni
Casado, Vicent
Lluis, Carme
Ferre, Sergi
Ortiz, Jordi
Canela, Enric
McCormick, Peter J.
TI Cocaine Disrupts Histamine H-3 Receptor Modulation of Dopamine D-1
Receptor Signaling: sigma(1)-D-1-H-3 Receptor Complexes as Key Targets
for Reducing Cocaine's Effects
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID PROXIMITY LIGATION ASSAY; SIGMA-1 RECEPTORS; STRIATAL SLICES;
BETA-ARRESTINS; AGONISTS; RAT; HETEROMERS; DISEASE; ACTIVATION;
MECHANISMS
AB The general effects of cocaine are not well understood at the molecular level. What is known is that the dopamine D-1 receptor plays an important role. Here we show that a key mechanism may be cocaine's blockade of the histamine H-3 receptor-mediated inhibition of D-1 receptor function. This blockade requires the sigma(1) receptor and occurs upon cocaine binding to sigma(1)-D-1-H-3 receptor complexes. The cocaine-mediated disruption leaves an uninhibited D-1 receptor that activates G(s), freely recruits beta-arrestin, increases p-ERK 1/2 levels, and induces cell death when over activated. Using in vitro assays with transfected cells and in ex vivo experiments using both rats acutely treated or self-administered with cocaine along with mice depleted of sigma(1) receptor, we show that blockade of sigma(1) 1 receptor by an antagonist restores the protective H-3 receptor-mediated brake on D-1 receptor signaling and prevents the cell death from elevated D-1 receptor signaling. These findings suggest that a combination therapy of sigma R-1 antagonists with H-3 receptor agonists could serve to reduce some effects of cocaine.
C1 [Moreno, Estefania; Moreno-Delgado, David; Navarro, Gemma; Gasperini, Paola; Rodriguez-Ruiz, Mar; Medrano, Mireia; Mallol, Josefa; Cortes, Antoni; Casado, Vicent; Lluis, Carme; Canela, Enric; McCormick, Peter J.] Univ Barcelona, Fac Biol, Ctr Invest Biomed Red Enfermedades Neurodegenerat, E-08028 Barcelona, Spain.
[Moreno, Estefania; Moreno-Delgado, David; Navarro, Gemma; Gasperini, Paola; Rodriguez-Ruiz, Mar; Medrano, Mireia; Mallol, Josefa; Cortes, Antoni; Casado, Vicent; Lluis, Carme; Canela, Enric; McCormick, Peter J.] Univ Barcelona, Fac Biol, Inst Biomed, E-08028 Barcelona, Spain.
[Moreno, Estefania; Moreno-Delgado, David; Navarro, Gemma; Gasperini, Paola; Rodriguez-Ruiz, Mar; Medrano, Mireia; Mallol, Josefa; Cortes, Antoni; Casado, Vicent; Lluis, Carme; Canela, Enric; McCormick, Peter J.] Univ Barcelona, Fac Biol, Dept Biochem & Mol Biol, E-08028 Barcelona, Spain.
[Hoffmann, Hanne M.; Fuentes, Silvia; Rosell-Vilar, Santi; Ortiz, Jordi] Univ Autonoma Barcelona, Fac Med, Inst Neurosci, Bellaterra 08193, Spain.
[Hoffmann, Hanne M.; Fuentes, Silvia; Rosell-Vilar, Santi; Ortiz, Jordi] Univ Autonoma Barcelona, Fac Med, Dept Biochem & Mol Biol, Bellaterra 08193, Spain.
[Ferre, Sergi] Natl Inst Drug Abuse, NIH, Dept Hlth & Human Serv, Intramural Res Program, Baltimore, MD 21224 USA.
[McCormick, Peter J.] Univ E Anglia, Sch Pharm, Norwich NR4 7TJ, Norfolk, England.
RP McCormick, PJ (reprint author), Univ E Anglia, Sch Pharm, Norwich Res Pk, Norwich NR4 7TJ, Norfolk, England.
EM p.mccormick@uea.ac.uk
RI McCormick, Peter/E-7387-2012; Ferre, Sergi/K-6115-2014; Ortiz,
Jordi/E-9018-2011; Fuentes Garcia, Silvia/B-4827-2014; Casado,
Vicent/K-1660-2014; Canela, Enric I./M-8726-2013
OI McCormick, Peter/0000-0002-2225-5181; Ferre, Sergi/0000-0002-1747-1779;
Ortiz, Jordi/0000-0002-9748-2290; Moreno, Estefania/0000-0002-2491-5753;
Canela, Enric I./0000-0003-4992-7440
FU Spanish Ministerio de Ciencia y Tecnologia [SAF2010-18472,
SAF2011-23813, SAF2006-08240, SAF2009-12510]; Spanish Ministerio de
Ciencia y Tecnologia (Red de Trastornos Adictivos) [RD06/0001/0015];
Intramural Funds of the National Institute on Drug Abuse
FX This study was supported by grants from the Spanish Ministerio de
Ciencia y Tecnologia (SAF2010-18472, SAF2011-23813, SAF2006-08240,
SAF2009-12510, and Red de Trastornos Adictivos RD06/0001/0015) and by
Intramural Funds of the National Institute on Drug Abuse to S. Ferre.
P.J.M. is a Ramon y Cajal Fellow. We thank Jasmina Jimenez for technical
help (University of Barcelona). We thank Laboratorios Esteve (Barcelona,
Spain) for providing sigma 1 receptor KO and WT mice brains.
NR 53
TC 18
Z9 19
U1 0
U2 10
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD MAR 5
PY 2014
VL 34
IS 10
BP 3545
EP 3558
DI 10.1523/JNEUROSCI.4147-13.2014
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA AC7HN
UT WOS:000332698900010
PM 24599455
ER
PT J
AU Nienborg, H
Cumming, BG
AF Nienborg, Hendrikje
Cumming, Bruce G.
TI Decision-Related Activity in Sensory Neurons May Depend on the Columnar
Architecture of Cerebral Cortex
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE choice probability; decision; orientation discrimination; striate
cortex; V1
ID VISUAL AREA MT; INFERIOR TEMPORAL CORTEX; CHOICE-RELATED ACTIVITY;
PSYCHOPHYSICAL PERFORMANCE; FUNCTIONAL-ORGANIZATION; NEURAL ACTIVITY;
TASK STRATEGY; V1 NEURONS; V2 NEURONS; MACAQUE MT
AB Many studies have reported correlations between the activity of sensory neurons and animals' judgments in discrimination tasks. Here, we suggest that such neuron-behavior correlations may require a cortical map for the task relevant features. This would explain why studies using discrimination tasks based on disparity in area V1 have not found these correlations: V1 contains no map for disparity. This scheme predicts that activity of V1 neurons correlates with decisions in an orientation-discrimination task. To test this prediction, we trained two macaque monkeys in a coarse orientation discrimination task using band-pass-filtered dynamic noise. The two orientations were always 90 apart and task difficulty was controlled by varying the orientation bandwidth of the filter. While the trained animals performed this task, we recordedfromorientation-selectiveV1 neurons (n = 82, n = 31 for Monkey 1, n = 51 for Monkey 2). For both monkeys, we observed significant correlation (quantified as "choice probabilities") of the V1 activity with the monkeys' perceptual judgments (mean choice probability 0.54, p = 10(-5)). In one of these animals, we had previously measured choice probabilities in a disparity discrimination task in V1, which had been at chance (0.49, not significantly different from 0.5). The choice probabilities in this monkey for the orientation discrimination task were significantly larger than those for the disparity discrimination task (p = 0.032). These results are predicted by our suggestion that choice probabilities are only observed for cortical sensory neurons that are organized in maps for the task-relevant feature.
C1 [Nienborg, Hendrikje] NEI, Lab Sensorimotor Res, NIH, Bethesda, MD 20892 USA.
[Nienborg, Hendrikje; Cumming, Bruce G.] Univ Tubingen, Werner Reichardt Ctr Integrat Neurosci, D-72076 Tubingen, Germany.
RP Nienborg, H (reprint author), Werner Reichardt Ctr Integrat Neurosci, Otfried Mueller Str 25, D-72076 Tubingen, Germany.
EM hendrikje.nienborg@cin.uni-tuebingen.de
FU Intramural Research Program of the National Institutes of
Health-National Eye Institute; European Research Council
FX This work was supported by the Intramural Research Program of the
National Institutes of Health-National Eye Institute and a Starting
Independent Researcher grant to H.N. from the European Research Council
(project acronym: NEUROOPTOGEN). We thank Denise Parker and Beth Nagy
for excellent animal care.
NR 50
TC 21
Z9 21
U1 0
U2 6
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD MAR 5
PY 2014
VL 34
IS 10
BP 3579
EP 3585
DI 10.1523/JNEUROSCI.2340-13.2014
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA AC7HN
UT WOS:000332698900012
PM 24599457
ER
PT J
AU Wang, MH
Wang, X
Zhao, L
Ma, WX
Rodriguez, IR
Fariss, RN
Wong, WT
AF Wang, Minhua
Wang, Xu
Zhao, Lian
Ma, Wenxin
Rodriguez, Ignacio R.
Fariss, Robert N.
Wong, Wai T.
TI Macroglia-Microglia Interactions via TSPO Signaling Regulates Microglial
Activation in the Mouse Retina
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE DBI; gliosis; microglia; Muller cells; retina; TSPO
ID DIAZEPAM-BINDING INHIBITOR; PERIPHERAL BENZODIAZEPINE-RECEPTOR; PROTEIN
18 KDA; CULTURED RAT ASTROCYTES; GANGLION-CELL APOPTOSIS;
AMINO-ACID-SEQUENCE; TRANSLOCATOR PROTEIN; MACULAR DEGENERATION;
CHOLESTEROL TRANSPORT; STEROID-BIOSYNTHESIS
AB Chronic retinal inflammation in the form of activated microglia and macrophages are implicated in the etiology of neurodegenerative diseases of the retina, including age-related macular degeneration, diabetic retinopathy, and glaucoma. However, molecular biomarkers and targeted therapies for immune cell activation in these disorders are currently lacking. To address this, we investigated the involvement and role of translocator protein (TSPO), a biomarker of microglial and astrocyte gliosis in brain degeneration, in the context of retinal inflammation. Here, we find that TSPO is acutely and specifically upregulated in retinal microglia in separate mouse models of retinal inflammation and injury. Concomitantly, its endogenous ligand, diazepam-binding inhibitor (DBI), is upregulated in the macroglia of the mouse retina such as astrocytes and Muller cells. In addition, we discover that TSPO-mediated signaling in microglia via DBI-derived ligands negatively regulates features of microglial activation, including reactive oxygen species production, TNF-alpha expression and secretion, and microglial proliferation. The inducibility and effects of DBI-TSPO signaling in the retina reveal a mechanism of coordinated macroglia-microglia interactions, the function of which is to limit the magnitude of inflammatory responses after their initiation, facilitating a return to baseline quiescence. Our results indicate that TSPO is a promising molecular marker for imaging inflammatory cell activation in the retina and highlight DBI-TSPO signaling as a potential target for immodulatory therapies.
C1 [Wang, Minhua; Wang, Xu; Zhao, Lian; Ma, Wenxin; Wong, Wai T.] NEI, NIH, Unit Neuron Glia Interact Retinal Dis, Bethesda, MD 20892 USA.
[Rodriguez, Ignacio R.] NEI, NIH, Mech Retinal Dis Sect, Lab Retinal Cell & Mol Biol, Bethesda, MD 20892 USA.
[Fariss, Robert N.] NEI, NIH, Bethesda, MD 20892 USA.
RP Wong, WT (reprint author), NEI, NIH, Unit Neuron Glia Interact Retinal Dis, Bldg 6,Room 215, Bethesda, MD 20892 USA.
EM wongw@nei.nih.gov
RI Wong, Wai/B-6118-2017
OI Wong, Wai/0000-0003-0681-4016
FU National Eye Institute Intramural Research Program, National Institutes
of Health
FX This study was supported by funds from the National Eye Institute
Intramural Research Program, National Institutes of Health.
NR 85
TC 40
Z9 40
U1 2
U2 9
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD MAR 5
PY 2014
VL 34
IS 10
BP 3793
EP 3806
DI 10.1523/JNEUROSCI.3153-13.2014
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA AC7HN
UT WOS:000332698900031
PM 24599476
ER
PT J
AU Perrin, BS
Tian, Y
Fu, RQ
Grant, CV
Chekmenev, EY
Wieczorek, WE
Dao, AE
Hayden, RM
Burzynski, CM
Venable, RM
Sharma, M
Opella, SJ
Pastor, RW
Cotten, ML
AF Perrin, B. Scott, Jr.
Tian, Ye
Fu, Riqiang
Grant, Christopher V.
Chekmenev, Eduard Y.
Wieczorek, William E.
Dao, Alexander E.
Hayden, Robert M.
Burzynski, Caitlin M.
Venable, Richard M.
Sharma, Mukesh
Opella, Stanley J.
Pastor, Richard W.
Cotten, Myriam L.
TI High-Resolution Structures and Orientations of Antimicrobial Peptides
Piscidin 1 and Piscidin 3 in Fluid Bilayers Reveal Tilting, Kinking, and
Bilayer Immersion
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID SOLID-STATE NMR; MOLECULAR-DYNAMICS SIMULATION; MEMBRANE-ACTIVE
PEPTIDES; ALIGNED LIPID-BILAYERS; AUSTRALIAN TREE FROG; HYBRID STRIPED
BASS; ANTIBACTERIAL PEPTIDES; MODEL MEMBRANES; CHARGE-DISTRIBUTION; PORE
FORMATION
AB While antimicrobial peptides (AMPs) have been widely investigated as potential therapeutics, high-resolution structures obtained under biologically relevant conditions are lacking. Here, the high-resolution structures of the homologous 22-residue long AMPs piscidin 1 (p1) and piscidin 3 (p3) are determined in fluid-phase 3:1 phosphatidylcholine/phosphatidylglycerol (PC/PG) and 1:1 phosphatidylethanolamine/phosphatidylglycerol (PE/PG) bilayers to identify molecular features important for membrane destabilization in bacterial cell membrane mimics. Structural refinement of H-1-N-15 dipolar couplings and N-15 chemical shifts measured by oriented sample solid-state NMR and all-atom molecular dynamics (MD) simulations provide structural and orientational information of high precision and accuracy about these interfacially bound alpha-helical peptides. The tilt of the helical axis, tau, is between 83 degrees and 93 degrees with respect to the bilayer normal for all systems and analysis methods. The average azimuthal rotation, rho, is 235 degrees, which results in burial of hydrophobic residues in the bilayer. The refined NMR and MD structures reveal a slight kink at G13 that delineates two helical segments characterized by a small difference in their T angles (<10 degrees) and significant difference in their rho angles (similar to 25 degrees). Remarkably, the kink, at the end of a G(X)(4)G motif highly conserved among members of the piscidin family, allows p1 and p3 to adopt rho angles that maximize their hydrophobic moments. Two structural features differentiate the more potent pl from p3: p1 has a larger rho angle and less N-terminal fraying. The peptides have comparable depths of insertion in PC/PG, but p3 is 1.2 angstrom more deeply inserted than p1 in PE/PG. In contrast to the ideal a-helical structures typically assumed in mechanistic models of AMPs, p1 and p3 adopt disrupted alpha-helical backbones that correct for differences in the amphipathicity of their N- and C-ends, and their centers of mass lie similar to 1.2-3.6 angstrom below the plane defined by the C2 atoms of the lipid acyl chains.
C1 [Perrin, B. Scott, Jr.; Venable, Richard M.; Pastor, Richard W.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA.
[Tian, Ye; Grant, Christopher V.; Opella, Stanley J.] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA.
[Fu, Riqiang; Chekmenev, Eduard Y.] Natl High Magnet Field Lab, Tallahassee, FL 32310 USA.
[Wieczorek, William E.; Dao, Alexander E.; Hayden, Robert M.; Burzynski, Caitlin M.; Cotten, Myriam L.] Hamilton Coll, Dept Chem, Clinton, NY 13323 USA.
[Sharma, Mukesh] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
RP Cotten, ML (reprint author), Hamilton Coll, Dept Chem, Clinton, NY 13323 USA.
EM mcotten@hamilton.edu
OI Chekmenev, Eduard/0000-0002-8745-8801
FU National Science Foundation [CHE-0832571]; NIH, National Heart, Lung and
Blood Institute; National Institutes of Health [P41EB002031]; NSF
[DMR-1157490]; State of Florida; U.S. Department of Energy
FX This research was supported in part by a grant from the National Science
Foundation (CHE-0832571) and the Intramural Research Program of the NIH,
National Heart, Lung and Blood Institute, and utilized the
high-performance computational capabilities at the National Institutes
of Health, Bethesda, MD (NHLBI LoBoS cluster). This work also utilized
the Center for NMR Spectroscopy and Imaging of Proteins at the
University of California, San Diego supported by the National Institutes
of Health (P41EB002031). The authors are grateful for NMR time received
at the National High Magnetic Field Laboratory (NHMFL) supported by the
NSF Cooperative Agreement DMR-1157490, the State of Florida, and the
U.S. Department of Energy.
NR 92
TC 27
Z9 28
U1 3
U2 71
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0002-7863
J9 J AM CHEM SOC
JI J. Am. Chem. Soc.
PD MAR 5
PY 2014
VL 136
IS 9
BP 3491
EP 3504
DI 10.1021/ja411119m
PG 14
WC Chemistry, Multidisciplinary
SC Chemistry
GA AC7CN
UT WOS:000332684700029
PM 24410116
ER
PT J
AU Li, YL
Freudenthal, BD
Beard, WA
Wilson, SH
Schlick, T
AF Li, Yunlang
Freudenthal, Bret D.
Beard, William A.
Wilson, Samuel H.
Schlick, Tamar
TI Optimal and Variant Metal-Ion Routes in DNA Polymerase beta's
Conformational Pathways
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID ACTIVE-SITE; MOLECULAR-DYNAMICS; NUCLEOTIDE INCORPORATION; MINOR-GROOVE;
MECHANISM; SUBSTRATE; FIDELITY; CORRECT; CANCER; ENERGY
AB To interpret recent structures of the R283K mutant of human DNA repair enzyme DNA polymerase beta (pol beta) differing in the number of Mg2+ ions, we apply transition path sampling (TPS) to assess the effect of differing ion placement on the transition from the open one-metal to the closed two-metal state. We find that the closing pathway depends on the initial ion position, both in terms of the individual transition states and associated energies. The energy barrier of the conformational pathway varies from 25 to 58 kJ/mol, compared to the conformational energy barrier of 42 kJ/mol for the wild-type poi beta reported previously. Moreover, we find a preferred ion route located in the center of the enzyme, parallel to the DNA. Within this route, the conformational pathway is similar to that of the overall open to closed transition of pol beta, but outside it, especially when the ion starts near active site residues Arg258 and Asp 190, the conformational pathway diverges significantly. Our findings should apply generally to pol beta since R283K is relatively far from the active site; further experimental and computational work are required to confirm this. Our studies also underscore the common feature that less active mutants have less stable closed states than their open states, in marked contrast to the wild-type enzyme, where the closed state is significantly more stable than the open form.
C1 [Li, Yunlang; Schlick, Tamar] NYU, Dept Chem, New York, NY 10012 USA.
[Li, Yunlang; Schlick, Tamar] NYU, Courant Inst Math Sci, New York, NY 10012 USA.
[Freudenthal, Bret D.; Beard, William A.; Wilson, Samuel H.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Schlick, T (reprint author), NYU, Dept Chem, 251 Mercer St, New York, NY 10012 USA.
EM schlick@nyu.edu
FU NIH, National Institute of Environmental Health Sciences [Z01-ES050158];
NIH [1U19CA105010]
FX We thank Dr. Ravi Radhakrishnan for providing the initial scripts for
transition path sampling simulations. This work was supported in part by
the Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences (project number Z01-ES050158) and was in
association with NIH grant 1U19CA105010. The computations in this study
were conducted using the resources of the CCNI supported by the New York
State Foundation for Science, Technology and Innovation (NYSTAR), and
the Dell computer cluster by New York University Information Technology
Services (NYU ITS). Molecular images were generated using the
VMD35 programs.
NR 48
TC 4
Z9 4
U1 0
U2 10
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0002-7863
J9 J AM CHEM SOC
JI J. Am. Chem. Soc.
PD MAR 5
PY 2014
VL 136
IS 9
BP 3630
EP 3639
DI 10.1021/ja412701f
PG 10
WC Chemistry, Multidisciplinary
SC Chemistry
GA AC7CN
UT WOS:000332684700044
PM 24511902
ER
PT J
AU Lim, U
Kocarnik, JM
Bush, WS
Matise, TC
Caberto, C
Park, SL
Carlson, CS
Deelman, E
Duggan, D
Fesinmeyer, M
Haiman, CA
Henderson, BE
Hindorff, LA
Kolonel, LN
Peters, U
Stram, DO
Tiirikainen, M
Wilkens, LR
Wu, CY
Kooperberg, C
Le Marchand, L
AF Lim, Unhee
Kocarnik, Jonathan M.
Bush, William S.
Matise, Tara C.
Caberto, Christian
Park, Sungshim Lani
Carlson, Christopher S.
Deelman, Ewa
Duggan, David
Fesinmeyer, Megan
Haiman, Christopher A.
Henderson, Brian E.
Hindorff, Lucia A.
Kolonel, Laurence N.
Peters, Ulrike
Stram, Daniel O.
Tiirikainen, Maarit
Wilkens, Lynne R.
Wu, Chunyuan
Kooperberg, Charles
Le Marchand, Loic
TI Pleiotropy of Cancer Susceptibility Variants on the Risk of Non-Hodgkin
Lymphoma: The PAGE Consortium
SO PLOS ONE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; CHRONIC LYMPHOCYTIC-LEUKEMIA; MANTLE CELL
LYMPHOMA; 2ND PRIMARY CANCERS; MULTIETHNIC COHORT; FOLLICULAR LYMPHOMA;
INFLAMMATION GENES; COMPLEX DISEASES; COMMON VARIANTS; LOCI
AB Background: Risk of non-Hodgkin lymphoma (NHL) is higher among individuals with a family history or a prior diagnosis of other cancers. Genome-wide association studies (GWAS) have suggested that some genetic susceptibility variants are associated with multiple complex traits (pleiotropy).
Objective: We investigated whether common risk variants identified in cancer GWAS may also increase the risk of developing NHL as the first primary cancer.
Methods: As part of the Population Architecture using Genomics and Epidemiology (PAGE) consortium, 113 cancer risk variants were analyzed in 1,441 NHL cases and 24,183 controls from three studies (BioVU, Multiethnic Cohort Study, Women's Health Initiative) for their association with the risk of overall NHL and common subtypes [diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL)] using an additive genetic model adjusted for age, sex and ethnicity. Study-specific results for each variant were meta-analyzed across studies.
Results: The analysis of NHL subtype-specific GWAS SNPs and overall NHL suggested a shared genetic susceptibility between FL and DLBCL, particularly involving variants in the major histocompatibility complex region (rs6457327 in 6p21.33: FL OR = 1.29, p = 0.013; DLBCL OR = 1.23, p = 0.013; NHL OR = 1.22, p = 5.9 x E-05). In the pleiotropy analysis, six risk variants for other cancers were associated with NHL risk, including variants for lung (rs401681 in TERT: OR per C allele = 0.89, p = 3.7 x E-03; rs4975616 in TERT: OR per A allele = 0.90, p = 0.01; rs3131379 in MSH5: OR per T allele = 1.16, p = 0.03), prostate (rs7679673 in TET2: OR per C allele = 0.89, p = 5.7 x E-03; rs10993994 in MSMB: OR per T allele = 1.09, p = 0.04), and breast (rs3817198 in LSP1: OR per C allele = 1.12, p = 0.01) cancers, but none of these associations remained significant after multiple test correction.
Conclusion: This study does not support strong pleiotropic effects of non-NHL cancer risk variants in NHL etiology; however, larger studies are warranted.
C1 [Lim, Unhee; Caberto, Christian; Kolonel, Laurence N.; Tiirikainen, Maarit; Wilkens, Lynne R.; Le Marchand, Loic] Univ Hawaii, Program Epidemiol, Ctr Canc, Honolulu, HI 96822 USA.
[Kocarnik, Jonathan M.; Carlson, Christopher S.; Peters, Ulrike; Wu, Chunyuan; Kooperberg, Charles] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Bush, William S.] Vanderbilt Univ, Ctr Human Genet Res, Nashville, TN 37235 USA.
[Matise, Tara C.; Deelman, Ewa] Rutgers State Univ, Dept Genet, Piscataway, NJ USA.
[Park, Sungshim Lani; Haiman, Christopher A.; Henderson, Brian E.; Stram, Daniel O.] Univ So Calif, Dept Prevent Med, Kenneth Norris Jr Comprehens Canc Ctr, Keck Sch Med, Los Angeles, CA 90089 USA.
[Duggan, David] Translat Genom Res Inst, Phoenix, AZ USA.
[Fesinmeyer, Megan] Seattle Childrens Res Inst, Ctr Child Hlth Behav & Dev, Seattle, WA USA.
[Hindorff, Lucia A.] NHGRI, Div Genom Med, NIH, Bethesda, MD 20892 USA.
RP Lim, U (reprint author), Univ Hawaii, Program Epidemiol, Ctr Canc, Honolulu, HI 96822 USA.
EM ulim@cc.hawaii.edu
OI Bush, William/0000-0002-9729-6519; Tiirikainen,
Maarit/0000-0002-8124-3818
FU National Human Genome Research Institute (NHGRI); NHGRI PAGE program
[U01HG004802, U01HG004790, U01HG004798-01]; Johns Hopkins University
from NHLBI [N01-HV-48195]; Centers for Disease Control and Prevention;
Vanderbilt CTSA from NCATS/NIH [UL1 TR000445]; NHGRI; National Cancer
Institute [R37CA54281, R01 CA63, P01CA33619, U01CA136792, U01CA98758];
National Heart, Lung, and Blood Institute; NIH; U.S. Department of
Health and Human Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9,
32111-13, 32115, 32118-32119, 32122, 4210726, 42129-32, 44221]; NCI
[R25CA94880]; PAGE Coordinating Center [U01HG004801-01]; [U01HG004803];
[U01HG004798]; [U01HG004801]
FX The Population Architecture Using Genomics and Epidemiology (PAGE)
program is funded by the National Human Genome Research Institute
(NHGRI), supported by U01HG004803 (CALiCo), U01HG004798 (EAGLE),
U01HG004802 (MEC), U01HG004790 (WHI), and U01HG004801 (Coordinating
Center), and their respective NHGRI ARRA supplements. The complete list
of PAGE members can be found at http://www.pagestudy.org. The data and
materials included in this report result from collaboration between the
following studies: The "Epidemiologic Architecture for Genes Linked to
Environment (EAGLE)'' is funded through the NHGRI PAGE program
(U01HG004798-01 and its NHGRI ARRA supplement). Genotyping services for
select NHANES III SNPs presented here were also provided by the Johns
Hopkins University under federal contract number (N01-HV-48195) from
NHLBI. The study participants derive from the National Health and
Nutrition Examination Surveys (NHANES), and these studies are supported
by the Centers for Disease Control and Prevention. The dataset used for
the analyses described were obtained from Vanderbilt University Medical
Center's BioVU which is supported by institutional funding and by the
Vanderbilt CTSA grant UL1 TR000445 from NCATS/NIH. The Multiethnic
Cohort study (MEC) characterization of epidemiological architecture is
funded through the NHGRI PAGE program (U01HG004802 and its NHGRI ARRA
supplement). The MEC study is funded through the National Cancer
Institute (R37CA54281, R01 CA63, P01CA33619, U01CA136792, and
U01CA98758). Funding support for the "Epidemiology of putative genetic
variants: The Women's Health Initiative'' study is provided through the
NHGRI PAGE program (U01HG004790 and its NHGRI ARRA supplement). The WHI
program is funded by the National Heart, Lung, and Blood Institute; NIH;
and U.S. Department of Health and Human Services through contracts
N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115,
32118-32119, 32122, 4210726, 42129-32, and 44221. A full listing of WHI
investigators can be found at:
http://www.whiscience.org/publications/WHI_investigators_shortlist. pdf.
Additional support for Dr. Kocarnik was provided by R25CA94880 from NCI.
Assistance with phenotype harmonization, SNP selection and annotation,
data cleaning, data management, integration and dissemination, and
general study coordination was provided by the PAGE Coordinating Center
(U01HG004801-01 and its NHGRI ARRA supplement). The National Institutes
of Mental Health also contributes to the support for the Coordinating
Center. The funders had no role in study design, data collection and
analysis, or preparation of the manuscript.
NR 41
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U1 0
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 5
PY 2014
VL 9
IS 3
AR e89791
DI 10.1371/journal.pone.0089791
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC4GP
UT WOS:000332479400028
PM 24598796
ER
PT J
AU Luo, K
Zhang, H
Zavala, F
Biragyn, A
Espinosa, DA
Markham, RB
AF Luo, Kun
Zhang, Hong
Zavala, Fidel
Biragyn, Arya
Espinosa, Diego A.
Markham, Richard B.
TI Fusion of Antigen to a Dendritic Cell Targeting Chemokine Combined with
Adjuvant Yields a Malaria DNA Vaccine with Enhanced Protective
Capabilities
SO PLOS ONE
LA English
DT Article
ID PLASMODIUM-YOELII SPOROZOITES; FALCIPARUM CIRCUMSPOROZOITE PROTEIN;
CD8(+) T-CELLS; IMMUNE-RESPONSES; LIVER STAGES; IRRADIATED SPOROZOITES;
RHESUS MACAQUES; IN-VITRO; ANTITUMOR IMMUNITY; GENITAL HERPES
AB Although sterilizing immunity to malaria can be elicited by irradiated sporozoite vaccination, no clinically practical subunit vaccine has been shown to be capable of preventing the approximately 600,000 annual deaths attributed to this infection. DNA vaccines offer several potential advantages for a disease that primarily affects the developing world, but new approaches are needed to improve the immunogenicity of these vaccines. By using a novel, lipid-based adjuvant, Vaxfectin, to attract immune cells to the immunization site, in combination with an antigen-chemokine DNA construct designed to target antigen to immature dendritic cells, we elicited a humoral immune response that provided sterilizing immunity to malaria challenge in a mouse model system. The chemokine, MIP3 alpha CCL20, did not significantly enhance the cellular infiltrate or levels of cytokine or chemokine expression at the immunization site but acted with Vaxfectin to reduce liver stage malaria infection by orders of magnitude compared to vaccine constructs lacking the chemokine component. The levels of protection achieved were equivalent to those observed with irradiated sporozoites, a candidate vaccine undergoing development for further large scale clinical trial. Only vaccination with the combined regimen of adjuvant and chemokine provided 80-100% protection against the development of bloodstream infection. Treating the immunization process as requiring the independent steps of 1) attracting antigen-presenting cells to the site of immunization and 2) specifically directing vaccine antigen to the immature dendritic cells that initiate the adaptive immune response may provide a rational strategy for the development of a clinically applicable malaria DNA vaccine.
C1 [Luo, Kun; Zhang, Hong; Zavala, Fidel; Espinosa, Diego A.; Markham, Richard B.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21218 USA.
[Biragyn, Arya] NIA, Immunoregulat Sect, Lab Mol Biol & Immunol, Baltimore, MD 21224 USA.
RP Markham, RB (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21218 USA.
EM rmarkham@jhsph.edu
OI Espinosa, Diego A./0000-0002-4364-5031
FU National Institutes of Health [AI073619]; Johns Hopkins University
Malaria Research Institute
FX This work was supported by grants from the National Institutes of Health
(Grant #AI073619) and the Johns Hopkins University Malaria Research
Institute (http://malaria.jhsph.edu). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 94
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Z9 5
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 5
PY 2014
VL 9
IS 3
AR e90413
DI 10.1371/journal.pone.0090413
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC4GP
UT WOS:000332479400072
PM 24599116
ER
PT J
AU Olson, SH
Parmley, J
Soos, C
Gilbert, M
Latorre-Margalef, N
Hall, JS
Hansbro, PM
Leighton, F
Munster, V
Joly, D
AF Olson, Sarah H.
Parmley, Jane
Soos, Catherine
Gilbert, Martin
Latorre-Margalef, Neus
Hall, Jeffrey S.
Hansbro, Phillip M.
Leighton, Frederick
Munster, Vincent
Joly, Damien
TI Sampling Strategies and Biodiversity of Influenza A Subtypes in Wild
Birds
SO PLOS ONE
LA English
DT Article
ID PATHOGENIC AVIAN INFLUENZA; MIGRATORY BIRDS; VIRUS; SURVEILLANCE;
WATERFOWL; PREVALENCE; PREDICTION; RICHNESS; PATTERNS; DUCKS
AB Wild aquatic birds are recognized as the natural reservoir of avian influenza A viruses (AIV), but across high and low pathogenic AIV strains, scientists have yet to rigorously identify most competent hosts for the various subtypes. We examined 11,870 GenBank records to provide a baseline inventory and insight into patterns of global AIV subtype diversity and richness. Further, we conducted an extensive literature review and communicated directly with scientists to accumulate data from 50 non-overlapping studies and over 250,000 birds to assess the status of historic sampling effort. We then built virus subtype sample-based accumulation curves to better estimate sample size targets that capture a specific percentage of virus subtype richness at seven sampling locations. Our study identifies a sampling methodology that will detect an estimated 75% of circulating virus subtypes from a targeted bird population and outlines future surveillance and research priorities that are needed to explore the influence of host and virus biodiversity on emergence and transmission.
C1 [Olson, Sarah H.; Gilbert, Martin] Wildlife Conservat Soc, Bronx, NY USA.
[Parmley, Jane] Univ Guelph, Dept Pathobiol, Canadian Cooperat Wildlife Hlth Ctr, Guelph, ON N1G 2W1, Canada.
[Soos, Catherine] Environm Canada, Sci & Technol Branch, Saskatoon, SK, Canada.
[Latorre-Margalef, Neus] Linnaeus Univ, Ctr Ecol & Evolut Microbial Model Syst EEMiS, Kalmar, Sweden.
[Latorre-Margalef, Neus] Univ Georgia, Coll Vet Med, Dept Populat Hlth, Southeastern Cooperat Wildlife Dis Study, Athens, GA USA.
[Hall, Jeffrey S.] USGS, Natl Wildlife Hlth Ctr, Madison, WI USA.
[Hansbro, Phillip M.] Univ Newcastle, Prior Res Ctr Asthma & Resp Dis, Newcastle, NSW 2300, Australia.
[Hansbro, Phillip M.] Hunter Med Res Inst, Newcastle, NSW, Australia.
[Leighton, Frederick] Univ Saskatchewan, Western Coll Vet Med, Canadian Cooperat Wildlife Hlth Ctr, Saskatoon, SK S7N 0W0, Canada.
[Munster, Vincent] NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT USA.
[Joly, Damien] Metabiota, Nanaimo, BC, Canada.
RP Joly, D (reprint author), Metabiota, Nanaimo, BC, Canada.
EM djoly@metabiota.com
OI Hall, Jeffrey/0000-0001-5599-2826; Munster, Vincent/0000-0002-2288-3196
FU Division of Intramural Research, National Institute of Allergy and
Infectious Disease, National Institutes of Health; National Institute of
Allergy and Infectious Diseases, National Institutes of Health (NIH);
Department of Health and Human Services [HHSN266200700007C]
FX This study was made possible by the generous support of the American
people through the United States Agency for International Development
(USAID) Emerging Pandemic Threats program, PREDICT project. VJM is
supported by the Division of Intramural Research, National Institute of
Allergy and Infectious Disease, National Institutes of Health.
Additional funding for this work was provided by the National Institute
of Allergy and Infectious Diseases, National Institutes of Health (NIH),
and the Department of Health and Human Services under contract
HHSN266200700007C. Journal access was provided by in-kind support from
the University of Wisconsin-Madison Center for Sustainability and the
Global Environment (SAGE). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 50
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U1 0
U2 17
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 5
PY 2014
VL 9
IS 3
AR e90826
DI 10.1371/journal.pone.0090826
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC4GP
UT WOS:000332479400137
PM 24599502
ER
PT J
AU Onwuamah, CK
Ekama, SO
Audu, RA
Ezechi, OC
Poirier, MC
Odeigah, PGC
AF Onwuamah, Chika K.
Ekama, Sabdat O.
Audu, Rosemary A.
Ezechi, Oliver C.
Poirier, Miriam C.
Odeigah, Peter G. C.
TI Exposure of Allium cepa Root Cells to Zidovudine or Nevirapine Induces
Cytogenotoxic Changes
SO PLOS ONE
LA English
DT Article
ID REVERSE-TRANSCRIPTASE INHIBITORS; HUMAN LYMPHOBLASTOID-CELLS; UNINFECTED
CHILDREN BORN; HIV-INFECTED WOMEN; IN-VITRO EXPOSURE; PERINATAL
EXPOSURE; UTERO EXPOSURE; TRANSMISSION; GENOTOXICITY; CARCINOMA
AB Antiretroviral drugs have proved useful in the clinical management of HIV-infected persons, though there are concerns about the effects of exposure to these DNA-reactive drugs. We investigated the potential of the plant model Allium cepa root tip assay to demonstrate the cytogenotoxicity of zidovudine and nevirapine and as a replace-reduce-refine programme amenable to resource-poor research settings. Cells mitotic index were determined in squashed root cells from Allium cepa bulbs exposed to zidovudine or nevirapine for 48 hr. The concentration of zidovudine and nevirapine inhibiting 50% root growth after 96 hr exposure was 65.0 mu M and 92.5 mu M respectively. Root length of all antiretroviral-exposed roots after 96 hr exposure was significantly shorter than the unexposed roots while additional root growth during a subsequent 48 hr recovery period in the absence of drug was not significantly different. By ANOVA, there was a significant association between percentage of cells in mitosis and zidovudine dose (p = 0.004), but not nevirapine dose (p = 0.68). Chromosomal aberrations such as sticky chromosomes, chromatin bridges, multipolar mitoses and binucleated cells were observed in root cells exposed to zidovudine and nevirapine for 48 hr. The most notable chromosomal aberration was drug-related increases in sticky chromosomes. Overall, the study showed inhibition in root length growth, changes in the mitotic index, and the induction of chromosomal aberrations in Allium bulbs treated for 96 hr or 48 hr with zidovudine and nevirapine. The study reveals generalized cytogenotoxic damage induced by exposure to zidovudine and nevirapine, and further show that the two compounds differ in their effects on mitosis and the types of chromosomal aberrations induced.
C1 [Onwuamah, Chika K.; Audu, Rosemary A.] Nigerian Inst Med Res, Human Virol Lab, Lagos, Nigeria.
[Ekama, Sabdat O.; Ezechi, Oliver C.] Nigerian Inst Med Res, Div Clin Sci, Lagos, Nigeria.
[Poirier, Miriam C.] NCI, Carcinogen DNA Interact Sect, LCBG, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Odeigah, Peter G. C.] Univ Lagos, Dept Cell Biol & Genet, Lagos, Nigeria.
RP Onwuamah, CK (reprint author), Nigerian Inst Med Res, Human Virol Lab, Lagos, Nigeria.
EM chikaonwuamah@yahoo.com
FU Intramural research program of the Centre for Cancer Research, National
Cancer Institute, National Institutes of Health, Bethesda, MD, USA
FX This work was self-sponsored by Dr Onwuamah as part of his doctoral
research. Dr Poirier also provided some reagents and she is supported by
the Intramural research program of the Centre for Cancer Research,
National Cancer Institute, National Institutes of Health, Bethesda, MD,
USA. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 18
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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 MAR 5
PY 2014
VL 9
IS 3
AR e90296
DI 10.1371/journal.pone.0090296
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC4GP
UT WOS:000332479400060
PM 24599327
ER
PT J
AU Zarin, DA
Tse, T
Menikoff, J
AF Zarin, Deborah A.
Tse, Tony
Menikoff, Jerry
TI Federal Human Research Oversight of Clinical Trials in the United States
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Letter
C1 [Zarin, Deborah A.; Tse, Tony] NIH, Natl Lib Med, Bethesda, MD 20894 USA.
[Menikoff, Jerry] US Dept HHS, Off Human Res Protect, Rockville, MD USA.
RP Zarin, DA (reprint author), NIH, 8600 Rockville Pike,Bldg 38A,Room 07N719, Bethesda, MD 20894 USA.
EM dzarin@mail.nih.gov
FU Intramural NIH HHS [Z99 LM999999]
NR 4
TC 2
Z9 2
U1 0
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD MAR 5
PY 2014
VL 311
IS 9
BP 960
EP 961
DI 10.1001/jama.2013.284306
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA AC0FS
UT WOS:000332170800026
PM 24595782
ER
PT J
AU Faroqi-Shah, Y
Kling, T
Solomon, J
Liu, SY
Park, G
Braun, A
AF Faroqi-Shah, Yasmeen
Kling, Therese
Solomon, Jeffrey
Liu, Siyuan
Park, Grace
Braun, Allen
TI Lesion analysis of language production deficits in aphasia
SO APHASIOLOGY
LA English
DT Article
DE Inferior frontal gyrus; Insula; Planum temporale.; Superior temporal
gyrus; Lesion analysis; Repetition; Aphasia; Sentence production
ID SENSORY-MOTOR INTEGRATION; SPEECH PRODUCTION; PLANUM TEMPORALE; BASAL
GANGLIA; BROCAS AREA; SENTENCE COMPREHENSION; CONDUCTION APHASIA;
ANTERIOR INSULA; STROKE PATIENTS; NEURAL BASIS
AB Background: Three aspects of language production are impaired to different degrees in individuals with post-stroke aphasia: ability to repeat words and nonwords, name pictures, and produce sentences. These impairments often persist into the chronic stages, and the neuroanatomical distribution of lesions associated with chronicity of each of these impairments is incompletely understood. Aims: The primary objective of this study was to investigate the lesion correlates of picture naming, sentence production, and nonword repetition deficits in the same participant group because most prior lesion studies have mapped single language impairments. The broader goal of this study was to investigate the extent and degree of overlap and uniqueness among lesions resulting in these deficits in order to advance the current understanding of functional subdivision of neuroanatomical regions involved in language production. Methods & Procedures: In this study, lesion-symptom mapping was used to determine if specific cortical regions are associated with nonword repetition, picture naming, and sentence production scores. Structural brain images and behavioural performance of 31 individuals with post-stroke left hemisphere lesions and a diagnosis of aphasia were used in the lesion analysis. Outcomes & Results: Each impairment was associated with mostly unique, but a few shared lesions. Overall, sentence and repetition deficits were associated with left anterior perisylvian lesions, including the pars opercularis and triangularis of the inferior frontal lobe, anterior superior temporal gyrus, anterior portions of the supramarginal gyrus, the putamen, and anterior portions of the insula. In contrast, impaired picture naming was associated with posterior perisylvian lesions including major portions of the inferior parietal lobe and middle temporal gyrus. The distribution of lesions in the insula was consistent with this antero-posterior perisylvian gradient. Significant voxels in the posterior planum temporale were associated with a combination of all three deficits. Conclusions: These findings emphasise the participation of each perisylvian region in multiple linguistic functions, suggesting a many(functions)-to-many(networks) framework while also identifying functional subdivisions within each region.
C1 [Faroqi-Shah, Yasmeen] Univ Maryland, Dept Hearing & Speech Sci, College Pk, MD 20742 USA.
[Kling, Therese] Johns Hopkins Univ Hosp, Baltimore, MD 21205 USA.
[Solomon, Jeffrey] Med Numer, Germantown, MD USA.
[Liu, Siyuan; Park, Grace; Braun, Allen] NIDCD, Bethesda, MD USA.
RP Faroqi-Shah, Y (reprint author), Univ Maryland, Dept Hearing & Speech Sci, College Pk, MD 20742 USA.
EM yfshah@umd.edu
NR 104
TC 2
Z9 2
U1 8
U2 27
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND
SN 0268-7038
EI 1464-5041
J9 APHASIOLOGY
JI Aphasiology
PD MAR 4
PY 2014
VL 28
IS 3
BP 258
EP 277
DI 10.1080/02687038.2013.853023
PG 20
WC Clinical Neurology
SC Neurosciences & Neurology
GA AH3DK
UT WOS:000336001900001
ER
PT J
AU Li, JJ
Agarwal, SK
Alonso, A
Blecker, S
Chamberlain, AM
London, SJ
Loehr, LR
McNeill, AM
Poole, C
Soliman, EZ
Heiss, G
AF Li, Jingjing
Agarwal, Sunil K.
Alonso, Alvaro
Blecker, Saul
Chamberlain, Alanna M.
London, Stephanie J.
Loehr, Laura R.
McNeill, Ann Marie
Poole, Charles
Soliman, Elsayed Z.
Heiss, Gerardo
TI Airflow Obstruction, Lung Function, and Incidence of Atrial Fibrillation
The Atherosclerosis Risk in Communities (ARIC) Study
SO CIRCULATION
LA English
DT Article
DE atrial fibrillation; forced expiratory volume; pulmonary disease;
chronic obstructive; respiratory physiological phenomena; risk factors;
vital capacity
ID ACQUIRED PNEUMONIA; PULMONARY VEINS; ISCHEMIC-STROKE; HEART-DISEASE;
COPD; INFLAMMATION; EPIDEMIOLOGY; HYPERTENSION; ASSOCIATION; PREVALENCE
AB Background Reduced low forced expiratory volume in 1 second (FEV1) is reportedly associated with an increased risk of atrial fibrillation (AF). Extant reports do not provide separate estimates for never smokers or for blacks, who incongruously have lower AF incidence than whites.
Methods and Results We examined 15 004 middle-aged blacks and whites enrolled in the Atherosclerosis Risk in Communities (ARIC) cohort study. Standardized spirometry data were collected at the baseline examination. Incident AF was identified from the first among the following: International Classification of Diseases codes for AF on hospital discharge records or death certificates or 12-lead ECGs performed during 3 triennial follow-up visits. Over an average follow-up of 17.5 years, a total of 1691 participants (11%) developed new-onset AF. The rate of incident AF was inversely associated with FEV1 in each of the 4 race and sex groups. After multivariable adjustment for traditional cardiovascular disease risk factors and height, hazard ratios of AF comparing the lowest with the highest quartile of FEV1 were 1.37 (95% confidence interval, 1.02-1.83) for white women, 1.49 (95% confidence interval, 1.16-1.91) for white men, 1.63 (95% confidence interval, 1.00-2.66) for black women, and 2.36 (95% confidence interval, 1.30-4.29) for black men. The above associations were observed across all smoking status categories. Moderate/severe airflow obstruction (FEV1/forced vital capacity <0.70 and FEV1 < 80% of predicted value) was also associated with higher AF incidence.
Conclusions In this large population-based study with a long-term follow-up, reduced FEV1 and obstructive respiratory disease were associated with a higher AF incidence after adjustment for measured confounders.
C1 [Li, Jingjing; Loehr, Laura R.; McNeill, Ann Marie; Poole, Charles; Heiss, Gerardo] Univ N Carolina, Chapel Hill, NC USA.
[Agarwal, Sunil K.] Johns Hopkins Univ, Baltimore, MD 21287 USA.
[Alonso, Alvaro] Univ Minnesota, Minneapolis, MN USA.
[Blecker, Saul] NYU, Med Ctr, New York, NY 10016 USA.
[Chamberlain, Alanna M.] Mayo Clin, Rochester, MN USA.
[London, Stephanie J.] NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Soliman, Elsayed Z.] Wake Forest Univ, Winston Salem, NC 27109 USA.
RP Agarwal, SK (reprint author), Johns Hopkins Univ, 2020 E Monument St,Room B-321, Baltimore, MD 21287 USA.
EM sunilagarwal@jhu.edu
RI Alonso, Alvaro/A-4917-2010;
OI Alonso, Alvaro/0000-0002-2225-8323; London,
Stephanie/0000-0003-4911-5290
FU National Heart, Lung, and Blood Institute (NHLBI) [N01-HC-55015,
N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021,
N01-HC-55022]; NHLBI [T32-HL-007779, IRC1HL099452-01]; American Heart
Association [09SDG2280087]; National Institutes of Health/NHLBI
[T32HL007024]
FX This research was sponsored by National Heart, Lung, and Blood Institute
(NHLBI) contracts N01-HC-55015, -55016, -55018, -55019, -55020, -55021,
and -55022. Dr Chamberlain was supported by NHLBI grant T32-HL-007779.
Additional funding for this study was provided by grants 09SDG2280087
from the American Heart Association and IRC1HL099452-01 from the NHLBI.
Dr Agarwal is supported by a National Institutes of Health/NHLBI
T32HL007024 Cardiovascular Epidemiology Training Grant.
NR 45
TC 22
Z9 22
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 4
PY 2014
VL 129
IS 9
BP 971
EP 980
DI 10.1161/CIRCULATIONAHA.113.004050
PG 10
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA AB9UF
UT WOS:000332140500009
PM 24344084
ER
PT J
AU Kojima, G
Bell, CL
Chen, R
Ross, GW
Abbott, RD
Launer, L
Lui, F
Masaki, K
AF Kojima, Gotaro
Bell, Christina L.
Chen, Randi
Ross, G. Webster
Abbott, Robert D.
Launer, Lenore
Lui, Felix
Masaki, Kamal
TI Low Dietary Vitamin D in Mid-Life Predicts Total Mortality in Men with
Hypertension: The Honolulu Heart Program
SO JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION
LA English
DT Article
DE vitamin D; mortality; hypertension; Japan; ethnology; Asian Americans
ID SERUM 25-HYDROXYVITAMIN D; CARDIOVASCULAR-DISEASE MORTALITY; RANDOMIZED
CONTROLLED-TRIAL; ALL-CAUSE MORTALITY; JAPANESE ANCESTRY; D DEFICIENCY;
POSTMENOPAUSAL WOMEN; GENERAL-POPULATION; ANGIOTENSIN-II; BLOOD-PRESSURE
AB Background: Vitamin D deficiency was associated with total mortality in previous epidemiological studies. Little is known about the effects of dietary vitamin D intake on mortality. We examined the association between mid-life dietary vitamin D intake and 45-year total mortality.
Methods: The Honolulu Heart Program is a longitudinal cohort study of 8006 Japanese American men in Hawaii aged 45 to 68 at baseline (1965-1968). Mid-life dietary vitamin D intake was calculated from 24-hour dietary recall using Nutritionist IV v3 software. We divided subjects into quartiles of dietary vitamin D. Total mortality data were available over 45years through 2010.
Results: Age-adjusted total mortality rates were higher in the lower quartiles of dietary vitamin D intake compared to the highest (p for trend = 0.011). Using Cox regression, low dietary vitamin D was significantly associated with total mortality; quartile (Q) 1 hazard ratio (HR) = 1.14, 95% confidence interval (95% CI) = 1.07-1.22, p < 0.001; Q2 HR = 1.11, 95% CI = 1.04-1.18, p = 0.002; and Q3 HR = 1.08, 95% CI = 1.01-1.15, p = 0.027; Q4 = reference. After adjusting for age, kilocalories, cardiovascular risk factors, and prevalent chronic diseases, only Q2 remained significant (HR = 1.08, 95% CI = 1.00-1.15, p = 0.037). Among hypertensive subjects only, those in the lower 2 quartiles had higher total mortality; Q1 HR = 1.12, 95% CI = 1.01-1.25, p = 0.039, and Q2 HR = 1.13, 95% CI = 1.02-1.26, p = 0.025, compared to Q4. There was no significant relationship in subjects without hypertension.
Conclusions: Low dietary vitamin D intake in mid-life was a weak predictor of total mortality over 45years of follow-up. We found a significant association between low dietary vitamin D intake and higher total mortality only among hypertensive subjects. Vitamin D may have cardioprotective effects.
C1 [Kojima, Gotaro; Bell, Christina L.; Ross, G. Webster; Abbott, Robert D.; Lui, Felix; Masaki, Kamal] Univ Hawaii, John A Burns Sch Med, Dept Geriatr Med, John A Hartford Fdn Ctr Excellence Geriatr, Honolulu, HI 96817 USA.
[Bell, Christina L.; Chen, Randi; Masaki, Kamal] Kuakini Med Ctr, Honolulu, HI USA.
[Ross, G. Webster] Vet Affairs Pacific Isl Hlth Care Syst, Honolulu, HI USA.
[Abbott, Robert D.] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA.
[Launer, Lenore] NIA, Bethesda, MD 20892 USA.
RP Kojima, G (reprint author), Univ Hawaii, John A Burns Sch Med, Dept Geriatr Med, 347 N Kuakini St HPM-9, Honolulu, HI 96817 USA.
EM gotarokojima@yahoo.co.jp
FU National Heart, Lung, and Blood Institute [N01-HC-05102]; National
Institute on Aging [N01-AG-4254-2149, U01-AG019349, R01-AG-038707,
R01-AG-027060]; Hawaii Community Foundation [2004-0463]; office for
Research and Development, Department of Veterans Affairs
FX This study was supported by contract N01-HC-05102 from The National
Heart, Lung, and Blood Institute; contract N01-AG-4254-2149, and grants
U01-AG019349, R01-AG-038707 and R01-AG-027060 from the National
Institute on Aging; the Hawaii Community Foundation (grant 2004-0463);
and the office for Research and Development, Department of Veterans
Affairs. The views expressed in this article do not necessarily
represent those of the federal government.
NR 41
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U1 2
U2 5
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND
SN 0731-5724
EI 1541-1087
J9 J AM COLL NUTR
JI J. Am. Coll. Nutr.
PD MAR 4
PY 2014
VL 33
IS 2
BP 129
EP 135
DI 10.1080/07315724.2013.875363
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA AE7DV
UT WOS:000334157800007
PM 24724770
ER
PT J
AU Marshall, RS
Festa, JR
Cheung, YK
Pavol, MA
Derdeyn, CP
Clarke, WR
Videen, TO
Grubb, RL
Slane, K
Powers, WJ
Lazar, RM
AF Marshall, Randolph S.
Festa, Joanne R.
Cheung, Ying-Kuen
Pavol, Marykay A.
Derdeyn, Colin P.
Clarke, William R.
Videen, Tom O.
Grubb, Robert L.
Slane, Kevin
Powers, William J.
Lazar, Ronald M.
CA RECON Investigators
TI Randomized Evaluation of Carotid Occlusion and Neurocognition (RECON)
trial Main results
SO NEUROLOGY
LA English
DT Article
ID HEMODYNAMIC CEREBRAL-ISCHEMIA; INTRACRANIAL BYPASS-SURGERY; COGNITIVE
IMPAIRMENT; AGE; STENOSIS; STATINS; ADULTS; ATORVASTATIN; PERFORMANCE;
POPULATION
AB Objective:To determine whether extracranial-intracranial (EC-IC) bypass can improve cognition over 2 years compared to best medical therapy alone in patients with symptomatic internal carotid artery (ICA) occlusion and increased oxygen extraction fraction (OEF) on PET.Methods:Patients underwent O-15 PET and were randomized if OEF ratio was >1.13 on the occluded side. Using blinded baseline and 2-year cognitive assessments, age-adjusted composite z scores were generated from subtests sensitive to right/left hemisphere plus global cognitive functioning. Multiple regression predicted 2-year cognitive change.Results:Eighty-nine patients were enrolled; 41 had increased OEF and were randomized. Two died, 2 were lost to follow-up, and 2 refused 2-year testing. Of the 35 remaining, 6 had ipsilateral stroke or death, leaving 13 surgical and 16 medical patients. Controlling for age, education, and depression, there was no difference in 2-year cognitive change between the medical and surgical arms (95% confidence interval -0.5 to 0.5, p = 0.9). In post hoc analysis of 26 patients with no stroke in the follow-up period, cognitive improvement was associated with less impaired PET OEF at baseline (p = 0.045).Conclusion:Cognitive improvement following bypass surgery was not superior to medical therapy among patients with recently symptomatic carotid occlusion and increased OEF. Among those with no recurrent stroke, less hemodynamic impairment at baseline was associated with greater cognitive gain in both groups. Reversing cognitive impairment in hemodynamic failure remains an open challenge.Classification of evidence:This study provides Class II evidence that for patients with symptomatic ICA occlusion and increased OEF on PET, EC-IC bypass compared to no bypass does not improve cognitive function after 2 years.
C1 [Marshall, Randolph S.; Cheung, Ying-Kuen; Pavol, Marykay A.; Slane, Kevin; Lazar, Ronald M.] Columbia Univ, Med Ctr, New York, NY 10027 USA.
[Festa, Joanne R.] St Lukes Roosevelt Med Ctr New York, New York, NY USA.
[Cheung, Ying-Kuen] NINDS, Bethesda, MD 20892 USA.
[Derdeyn, Colin P.; Videen, Tom O.; Grubb, Robert L.] Washington Univ, St Louis, MO USA.
[Clarke, William R.] Univ Iowa, Iowa City, IA USA.
[Powers, William J.] Univ N Carolina, Chapel Hill, NC USA.
RP Marshall, RS (reprint author), Columbia Univ, Med Ctr, New York, NY 10027 USA.
EM rsm2@columbia.edu
FU NINDS NIH HHS [5U01NS041895, NS048212, NS42167]
NR 41
TC 16
Z9 17
U1 1
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD MAR 4
PY 2014
VL 82
IS 9
BP 744
EP 751
DI 10.1212/WNL.0000000000000167
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA AG9OD
UT WOS:000335748100007
PM 24477109
ER
PT J
AU Houghton, LC
AF Houghton, L. C.
TI Becoming dedicated to the scarf: biocultural markers of growing up
British-Bangladeshi.
SO AMERICAN JOURNAL OF HUMAN BIOLOGY
LA English
DT Meeting Abstract
C1 [Houghton, L. C.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1042-0533
EI 1520-6300
J9 AM J HUM BIOL
JI Am. J. Hum. Biol.
PD MAR 4
PY 2014
VL 26
IS 2
BP 268
EP 268
PG 1
WC Anthropology; Biology
SC Anthropology; Life Sciences & Biomedicine - Other Topics
GA AB0DH
UT WOS:000331461500053
ER
PT J
AU Robbins, JB
Schneerson, R
Kubler-Kielb, J
Keith, JM
Trollfors, B
Vinogradov, E
Shiloach, J
AF Robbins, John B.
Schneerson, Rachel
Kubler-Kielb, Joanna
Keith, Jerry M.
Trollfors, Birger
Vinogradov, Evgeny
Shiloach, Joseph
TI Toward a new vaccine for pertussis
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE new pertussis vaccine; lipooligosaccharide conjugate
ID PROTEIN CONJUGATE VACCINE; INFLUENZAE TYPE-B; BORDETELLA-PERTUSSIS;
MONOCLONAL-ANTIBODIES; WHOOPING-COUGH; TOXOID VACCINE; BACTERICIDAL
ANTIBODIES; CAPSULAR POLYSACCHARIDE; SEROLOGIC RESPONSE; HOUSEHOLD
EXPOSURE
AB To overcome the limitations of the current pertussis vaccines, those of limited duration of action and failure to induce direct killing of Bordetella pertussis, a synthetic scheme was devised for preparing a conjugate vaccine composed of the Bordetella bronchiseptica core oligosaccharide with one terminal trisaccharide to aminooxylated BSA via their terminal ketodeoxyoctanate residues. Conjugate-induced antibodies, by a fraction of an estimated human dose injected into young outbred mice as a saline solution, were bactericidal against B. pertussis, and their titers correlated with their ELISA values. The carrier protein is planned to be genetically altered pertussis toxoid. Such conjugates are easy to prepare, stable, and should add both to the level and duration of immunity induced by current vaccine-induced pertussis antibodies and reduce the circulation of B. pertussis.
C1 [Kubler-Kielb, Joanna] NICHHD, NIH, Bethesda, MD 20892 USA.
[Shiloach, Joseph] NIDDK, NIH, Bethesda, MD 20892 USA.
[Trollfors, Birger] Sahlgrenska Hosp, Dept Pediat, S-41345 Gothenburg, Sweden.
[Vinogradov, Evgeny] CNR, Ottawa, ON K1A 0R6, Canada.
EM johnbennettrobbins@gmail.com
NR 87
TC 13
Z9 13
U1 0
U2 5
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAR 4
PY 2014
VL 111
IS 9
BP 3213
EP 3216
DI 10.1073/pnas.1324149111
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC5KR
UT WOS:000332560300019
PM 24556987
ER
PT J
AU Ishibashi, T
Dangkulwanich, M
Coello, Y
Lionberger, TA
Lubkowska, L
Ponticelli, AS
Kashlev, M
Bustamante, C
AF Ishibashi, Toyotaka
Dangkulwanich, Manchuta
Coello, Yves
Lionberger, Troy A.
Lubkowska, Lucyna
Ponticelli, Alfred S.
Kashlev, Mikhail
Bustamante, Carlos
TI Transcription factors IIS and IIF enhance transcription efficiency by
differentially modifying RNA polymerase pausing dynamics
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE optical tweezers; Pol II; yeast; enzyme kinetics
ID SACCHAROMYCES-CEREVISIAE TFIIF; STRUCTURAL BASIS; CHROMATIN TEMPLATES;
NUCLEOSOMAL BARRIER; ELONGATION; INITIATION; FIDELITY; CLEAVAGE; YEAST;
BACKTRACKING
AB Transcription factors IIS (TFIIS) and IIF (TFIIF) are known to stimulate transcription elongation. Here, we use a single-molecule transcription elongation assay to study the effects of both factors. We find that these transcription factors enhance overall transcription elongation by reducing the lifetime of transcriptional pauses and that TFIIF also decreases the probability of pause entry. Furthermore, we observe that both factors enhance the processivity of RNA polymerase II through the nucleosomal barrier. The effects of TFIIS and TFIIF are quantitatively described using the linear Brownian ratchet kinetic model for transcription elongation and the backtracking model for transcriptional pauses, modified to account for the effects of the transcription factors. Our findings help elucidate the molecular mechanisms by which transcription factors modulate gene expression.
C1 [Ishibashi, Toyotaka; Dangkulwanich, Manchuta; Coello, Yves; Lionberger, Troy A.; Bustamante, Carlos] Univ Calif Berkeley, Jason L Choy Lab Single Mol Biophys, Berkeley, CA 94720 USA.
[Ishibashi, Toyotaka; Dangkulwanich, Manchuta; Coello, Yves; Lionberger, Troy A.; Bustamante, Carlos] Univ Calif Berkeley, Calif Inst Quantitat Biosci, Berkeley, CA 94720 USA.
[Dangkulwanich, Manchuta; Lionberger, Troy A.; Bustamante, Carlos] Univ Calif Berkeley, Kavli Energy NanoSci Inst, Berkeley, CA 94720 USA.
[Dangkulwanich, Manchuta; Bustamante, Carlos] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
[Lionberger, Troy A.; Bustamante, Carlos] Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
[Lionberger, Troy A.; Bustamante, Carlos] Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA.
[Bustamante, Carlos] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
[Dangkulwanich, Manchuta; Lionberger, Troy A.; Bustamante, Carlos] Lawrence Berkeley Natl Lab, Phys Biosci Div, Berkeley, CA 94720 USA.
[Lubkowska, Lucyna; Kashlev, Mikhail] NCI, Ctr Canc Res, Frederick, MD 21702 USA.
[Ponticelli, Alfred S.] SUNY Buffalo, Sch Med & Biomed Sci, Dept Biochem, Buffalo, NY 14214 USA.
RP Ishibashi, T (reprint author), Univ Calif Berkeley, Jason L Choy Lab Single Mol Biophys, Berkeley, CA 94720 USA.
EM toyotakaishibashi@gmail.com; carlosb@berkeley.edu
OI Ishibashi, Toyotaka/0000-0001-8015-2319; Coello,
Yves/0000-0001-6243-5403
FU National Institutes of Health [R01-GM032543]; US Department of Energy,
Office of Basic Energy Sciences, Division of Materials Sciences and
Engineering [DE-AC02-05CH11231]
FX We thank Ms. Lian Lash-Rosenberg, Ms. Tran Do, and Dr. Cesar Diaz Celis
for experimental assistance. We also thank Dr. Chen Yang for providing
us a fraction of purified TFIIF. This work was supported in part by
grants from the National Institutes of Health (R01-GM032543) (to C. B.)
and the US Department of Energy, Office of Basic Energy Sciences,
Division of Materials Sciences and Engineering under Contract
DE-AC02-05CH11231 (to C.B.).
NR 40
TC 18
Z9 19
U1 3
U2 19
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAR 4
PY 2014
VL 111
IS 9
BP 3419
EP 3424
DI 10.1073/pnas.1401611111
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC5KR
UT WOS:000332560300056
PM 24550488
ER
PT J
AU Roche, J
Louis, JM
Grishaev, A
Ying, JF
Bax, A
AF Roche, Julien
Louis, John M.
Grishaev, Alexander
Ying, Jinfa
Bax, Adriaan
TI Dissociation of the trimeric gp41 ectodomain at the lipid-water
interface suggests an active role in HIV-1 Env-mediated membrane fusion
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE hemagglutinin; HIV-1 fusion inhibitor; RDC; N-15 relaxation; chemical
shift
ID ENVELOPE GLYCOPROTEIN; ATOMIC-STRUCTURE; VIRAL MEMBRANE; VIRUS ENVELOPE;
ENTRY; CONFORMATION; INHIBITION; CAPTURE; CORE
AB The envelope glycoprotein gp41 mediates the process of membrane fusion that enables entry of the HIV-1 virus into the host cell. The actual fusion process involves a switch from a homotrimeric prehairpin intermediate conformation, consisting of parallel coiled-coil helices, to a postfusion state where the ectodomains are arranged as a trimer of helical hairpins, adopting a six-helix bundle (6HB) state. Here, we show by solution NMR spectroscopy that a water-soluble 6HB gp41 ectodomain binds to zwitterionic detergents that contain phosphocholine or phosphatidylcholine head groups and phospholipid vesicles that mimic T-cell membrane composition. Binding results in the dissociation of the 6HB and the formation of a monomeric state, where its two a-helices, N-terminal heptad repeat (NHR) and C-terminal heptad repeat (CHR), become embedded in the lipid-water interface of the virus and host cell. The atomic structure of the gp41 ectodomain monomer, based on NOE distance restraints and residual dipolar couplings, shows that the NHR and CHR helices remain mostly intact, but they completely lose interhelical contacts. The high affinity of the ectodomain helices for phospholipid surfaces suggests that unzippering of the prehairpin intermediate leads to a state where the NHR and CHR helices become embedded in the host cell and viral membranes, respectively, thereby providing a physical force for bringing these membranes into close juxtaposition before actual fusion.
C1 [Roche, Julien; Louis, John M.; Grishaev, Alexander; Ying, Jinfa; Bax, Adriaan] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Bax, A (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM bax@nih.gov
RI Roche, Julien/O-3204-2013
OI Roche, Julien/0000-0003-3892-0200
FU National Institutes of Health Intramural Research Programs of the
National Institute of Diabetes and Digestive and Kidney Diseases;
Intramural AIDS-Targeted Antiviral Program of the Office of the
Director, National Institutes of Health; National Institute of Diabetes
and Digestive and Kidney Diseases MS facility
FX We thank Annie Aniana for help with protein expression and purification
and Robert Blumenthal and Leonid Chernomordik for helpful discussions,
and we acknowledge support from the National Institute of Diabetes and
Digestive and Kidney Diseases MS facility. This work was funded by the
National Institutes of Health Intramural Research Programs of the
National Institute of Diabetes and Digestive and Kidney Diseases and the
Intramural AIDS-Targeted Antiviral Program of the Office of the
Director, National Institutes of Health.
NR 42
TC 22
Z9 23
U1 2
U2 28
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAR 4
PY 2014
VL 111
IS 9
BP 3425
EP 3430
DI 10.1073/pnas.1401397111
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC5KR
UT WOS:000332560300057
PM 24550514
ER
PT J
AU Liao, W
Spolski, R
Li, P
Du, N
West, EE
Ren, M
Mitra, S
Leonard, WJ
AF Liao, Wei
Spolski, Rosanne
Li, Peng
Du, Ning
West, Erin E.
Ren, Min
Mitra, Suman
Leonard, Warren J.
TI Opposing actions of IL-2 and IL-21 on Th9 differentiation correlate with
their differential regulation of BCL6 expression
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID INTERLEUKIN-9-PRODUCING T-CELLS; GERMINAL CENTER FORMATION;
FOLLICULAR-HELPER-CELLS; IMMUNE-RESPONSES; T(H)17 CELLS; TGF-BETA;
INFLAMMATION; GENERATION; INDUCTION; STAT5
AB Interleukin 9 (IL-9) is a gamma(c)-family cytokine that is highly produced by T-helper 9 (Th9) cells and regulates a range of immune responses, including allergic inflammation. Here we show that IL-2-JAK3-STAT5 signaling is required for Th9 differentiation, with critical STAT5 binding sites in the Il9 (the gene encoding IL-9) promoter. IL-2 also inhibited B cell lymphoma 6 (BCL6) expression, and overexpression of BCL6 impaired Th9 differentiation. In contrast, IL-21 induced BCL6 and diminished IL-9 expression in wild-type but not Bcl6(-/-) cells, and Th9 differentiation was increased in Il21(-/-) and Il21r(-/-) T cells. Interestingly, BCL6 bound in proximity to many STAT5 and STAT6 binding sites, including at the Il9 promoter. Moreover, there was increased BCL6 and decreased STAT binding at this site in cells treated with blocking antibodies to IL-2 and the IL-2 receptor, suggesting a possible BCL6-STAT5 binding competition that influences IL-9 production. BCL6 binding was also increased when cells were Th9-differentiated in the presence of IL-21. Thus, our data reveal not only direct IL-2 effects via STAT5 at the Il9 gene, but also opposing actions of IL-2 and IL-21 on BCL6 expression, with increased BCL6 expression inhibiting IL-9 production. These data suggest a model in which increasing BCL6 expression decreases efficient Th9 differentiation, indicating possible distinctive approaches for controlling this process.
C1 [Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
NHLBI, Ctr Immunol, NIH, Bethesda, MD 20892 USA.
RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM wjl@helix.nih.gov
FU Division of Intramural Research, NHLBI, National Institutes of Health
FX We thank Dr. Jian-Xin Lin (National Heart, Lung, and Blood Institute,
Bethesda) for critical comments, Drs. Art Shaffer and Louis Staudt
(National Cancer Institute, Bethesda) for Bcl6-/- mice and
the human BCL6 retroviral expression vector, Dr. Lothar Hennighausen
(National Institute of Diabetes and Digestive and Kidney Diseases,
Bethesda) for the Stat5a/Stat5bfl/fl mice, and the DNA
Sequencing Core, NHLBI for generating ChIP-Seq and RNA-Seq libraries.
This work was supported by the Division of Intramural Research, NHLBI,
National Institutes of Health.
NR 41
TC 28
Z9 30
U1 0
U2 5
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAR 4
PY 2014
VL 111
IS 9
BP 3508
EP 3513
DI 10.1073/pnas.1301138111
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC5KR
UT WOS:000332560300071
PM 24550509
ER
PT J
AU Ma, HW
Thapa, A
Morris, L
Redmond, TM
Baehr, W
Ding, XQ
AF Ma, Hongwei
Thapa, Arjun
Morris, Lynsie
Redmond, T. Michael
Baehr, Wolfgang
Ding, Xi-Qin
TI Suppressing thyroid hormone signaling preserves cone photoreceptors in
mouse models of retinal degeneration
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID CELL-DEATH; DEVELOPMENTAL EXPRESSION; RETINITIS-PIGMENTOSA; OPSIN
EXPRESSION; DOWN-REGULATION; GENE DELIVERY; RECEPTOR; ACTIVATION;
APOPTOSIS; METAMORPHOSIS
AB Cone phototransduction and survival of cones in the human macula is essential for color vision and for visual acuity. Progressive cone degeneration in age-related macular degeneration, Stargardt disease, and recessive cone dystrophies is a major cause of blindness. Thyroid hormone (TH) signaling, which regulates cell proliferation, differentiation, and apoptosis, plays a central role in cone opsin expression and patterning in the retina. Here, we investigated whether TH signaling affects cone viability in inherited retinal degeneration mouse models. Retinol isomerase RPE65-deficient mice [a model of Leber congenital amaurosis (LCA) with rapid cone loss] and cone photoreceptor function loss type 1 mice (severe recessive achromatopsia) were used to determine whether suppressing TH signaling with antithyroid treatment reduces cone death. Further, cone cyclic nucleotide-gated channel B subunit-deficient mice (moderate achromatopsia) and guanylate cyclase 2e-deficient mice (LCA with slower cone loss) were used to determine whether triiodothyronine (T3) treatment (stimulating TH signaling) causes deterioration of cones. We found that cone density in retinol isomerase RPE65-deficient and cone photoreceptor function loss type 1 mice increased about sixfold following antithyroid treatment. Cone density in cone cyclic nucleotide-gated channel B subunit-deficient and guanylate cyclase 2e-deficient mice decreased about 40% following T3 treatment. The effect of TH signaling on cone viability appears to be independent of its regulation on cone opsin expression. This work demonstrates that suppressing TH signaling in retina dystrophy mouse models is protective of cones, providing insights into cone preservation and therapeutic interventions.
C1 [Ma, Hongwei; Thapa, Arjun; Morris, Lynsie; Ding, Xi-Qin] Univ Oklahoma, Hlth Sci Ctr, Dept Cell Biol, Oklahoma City, OK 73104 USA.
[Redmond, T. Michael] NEI, Lab Retinal Cell & Mol Biol, Bethesda, MD 20892 USA.
[Baehr, Wolfgang] Univ Utah, John A Moran Eye Ctr, Salt Lake City, UT 84132 USA.
RP Ding, XQ (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Cell Biol, Oklahoma City, OK 73104 USA.
EM xi-qin-ding@ouhsc.edu
OI Redmond, T. Michael/0000-0002-1813-5291
FU National Center for Research Resources [P20RR017703]; National Eye
Institute [P30EY12190, R01EY019490, R01EY08123]; Oklahoma Center for the
Advancement of Science and Technology
FX We thank Drs. Cheryl Craft and Muna Naash for providing antibodies for
M-opsin, cone arrestin, and S-opsin. This work was supported by grants
from the National Center for Research Resources (P20RR017703), the
National Eye Institute (P30EY12190, R01EY019490, and R01EY08123), and
the Oklahoma Center for the Advancement of Science and Technology.
NR 39
TC 11
Z9 12
U1 0
U2 14
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAR 4
PY 2014
VL 111
IS 9
BP 3602
EP 3607
DI 10.1073/pnas.1317041111
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC5KR
UT WOS:000332560300087
PM 24550448
ER
PT J
AU Gerlic, M
Croker, BA
Cengia, LH
Moayeri, M
Kile, BT
Masters, SL
AF Gerlic, Motti
Croker, Ben A.
Cengia, Louise H.
Moayeri, Mahtab
Kile, Benjamin T.
Masters, Seth L.
TI NLRP1a Expression in Srebp-1a-Deficient Mice
SO CELL METABOLISM
LA English
DT Letter
ID PYROPTOSIS
C1 [Gerlic, Motti; Cengia, Louise H.; Kile, Benjamin T.; Masters, Seth L.] Walter & Eliza Hall Inst Med Res, Parkville, Vic 3052, Australia.
[Gerlic, Motti; Kile, Benjamin T.; Masters, Seth L.] Univ Melbourne, Dept Med Biol, Parkville, Vic 3010, Australia.
[Croker, Ben A.] Harvard Univ, Boston Childrens Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02115 USA.
[Moayeri, Mahtab] NIAID, Microbial Pathogenesis Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Masters, SL (reprint author), Walter & Eliza Hall Inst Med Res, Parkville, Vic 3052, Australia.
EM masters@wehi.edu.au
OI gerlic, mordechay/0000-0001-9518-1833; Croker, Ben/0000-0002-0885-3599;
Kile, Benjamin/0000-0002-8836-8947; masters, seth/0000-0003-4763-576X
NR 6
TC 1
Z9 2
U1 0
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1550-4131
EI 1932-7420
J9 CELL METAB
JI Cell Metab.
PD MAR 4
PY 2014
VL 19
IS 3
BP 345
EP 346
DI 10.1016/j.cmet.2014.02.002
PG 2
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA AC3DP
UT WOS:000332395500001
PM 24606891
ER
PT J
AU Maio, N
Singh, A
Uhrigshardt, H
Saxena, N
Tong, WH
Rouault, TA
AF Maio, Nunziata
Singh, Anamika
Uhrigshardt, Helge
Saxena, Neetu
Tong, Wing-Hang
Rouault, Tracey A.
TI Cochaperone Binding to LYR Motifs Confers Specificity of Iron Sulfur
Cluster Delivery
SO CELL METABOLISM
LA English
DT Article
ID SUCCINATE-DEHYDROGENASE; SCAFFOLD PROTEIN; CLINICAL-FEATURES; IN-VIVO;
CHAPERONE; COMPLEX; GENE; PARAGANGLIOMA; BIOGENESIS; DOMAIN
AB Iron sulfur (Fe-S) clusters, preassembled on the ISCU scaffold, are transferred to target proteins or to intermediate scaffolds by a dedicated chaperone-cochaperone system. However, the molecular mechanisms that underlie substrate discrimination and guide delivery of nascent clusters to specific subsets of Fe-S recipients are poorly understood. Here, we identified interacting partners of the cochaperone HSC20 and discovered that LYR motifs are molecular signatures of specific recipient Fe-S proteins or accessory factors that assist Fe-S cluster delivery. In succinate dehydrogenase B, two LYR motifs engage the ISCU-HSC20-HSPA9 complex to aid incorporation of three Fe-S clusters within the final structure of complex II. Moreover, we show that members of the LYR motif family which assist assembly of complexes II or III, SDHAF1 and LYRM7, respectively, are HSC20 binding partners. Our studies unveil a network of interactions between HSC20 and LYR motif-containing proteins that are key to the assembly and function of complexes I, II, and III.
C1 [Maio, Nunziata; Singh, Anamika; Uhrigshardt, Helge; Saxena, Neetu; Tong, Wing-Hang; Rouault, Tracey A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Mol Med, Bethesda, MD 20892 USA.
RP Rouault, TA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Mol Med, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM rouault@mail.nih.gov
FU Eunice Kennedy Shriver NICHD Intramural Research Program
FX We are grateful to members of our lab for constructive discussions; to
Drs. J.S. Bonifacino, R. Mattera, and Y. Prabhu for providing advice on
the Y2H assay; to Dr. A. Banerjee for insights into the structural
aspects of our work; and to A. Sharma for the gift of antibodies to the
epitope tags. This work was supported by the Eunice Kennedy Shriver
NICHD Intramural Research Program.
NR 50
TC 35
Z9 37
U1 0
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1550-4131
EI 1932-7420
J9 CELL METAB
JI Cell Metab.
PD MAR 4
PY 2014
VL 19
IS 3
BP 445
EP 457
DI 10.1016/j.cmet.2014.01.015
PG 13
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA AC3DP
UT WOS:000332395500014
PM 24606901
ER
PT J
AU Gruschus, JM
Byrd, RA
Randazzo, PA
AF Gruschus, James M.
Byrd, R. Andrew
Randazzo, Paul A.
TI The Importance of Seeing Surface (Effects)
SO STRUCTURE
LA English
DT Editorial Material
ID MEMBRANE; GTPASE; RAS; RECOGNITION; BINDING; ARF1
AB In this issue of Structure, Liu and colleagues describe an experimentally rigorous and innovative approach for understanding the role of membranes in the function and regulation of peripheral membrane proteins. This work is the beginning of a new era of experimental work that promises many advances relevant to molecular mechanisms and therapeutic targeting of this important class of proteins.
C1 [Gruschus, James M.] NHLBI, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA.
[Byrd, R. Andrew] NCI, Struct Biophys Lab, NIH, Bethesda, MD 20892 USA.
[Randazzo, Paul A.] NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Randazzo, PA (reprint author), NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM randazzp@mail.nih.gov
RI Byrd, R. Andrew/F-8042-2015
OI Byrd, R. Andrew/0000-0003-3625-4232
FU Intramural NIH HHS [Z99 CA999999, ZIA BC007365-19]; NCI NIH HHS [Z01
BC007365]
NR 13
TC 1
Z9 1
U1 2
U2 10
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0969-2126
EI 1878-4186
J9 STRUCTURE
JI Structure
PD MAR 4
PY 2014
VL 22
IS 3
BP 363
EP 365
DI 10.1016/j.str.2014.02.005
PG 3
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA AD1WZ
UT WOS:000333025700002
PM 24607142
ER
PT J
AU Xiao, Q
Freedman, ND
Ren, J
Hollenbeck, AR
Abnet, CC
Park, Y
AF Xiao, Q.
Freedman, N. D.
Ren, J.
Hollenbeck, A. R.
Abnet, C. C.
Park, Y.
TI Intakes of folate, methionine, vitamin B6, and vitamin B12 with risk of
esophageal and gastric cancer in a large cohort study
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE folate; one-carbon metabolism pathway; esophageal cancer; gastric cancer
ID HEALTH-AMERICAN-ASSOCIATION; RETIRED-PERSONS DIET; NATIONAL-INSTITUTES;
NUTRIENT INTAKE; ADENOCARCINOMAS; POLYMORPHISMS; CARCINOMA; OBESITY;
MTHFR
AB Background: Nutrients in the one-carbon metabolism pathway may be involved in carcinogenesis. Few cohort studies have investigated the intakes of folate and related nutrients in relation to gastric and esophageal cancer.
Methods: We prospectively examined the association between self-reported intakes of folate, methionine, vitamin B6, and vitamin B12 and gastric and esophageal cancer in 492 293 men and women.
Results: We observed an elevated risk of esophageal squamous cell carcinoma with low intake of folate (relative risk (95% confidence interval): Q1 vs Q3, 1.91 (1.17, 3.10)), but no association with high intake. Folate intake was not associated with esophageal adenocarcinoma, gastric cardia adenocarcinoma, or non-cardia gastric adenocarcinoma. The intakes of methionine, vitamin B6, and vitamin B12 were not associated with esophageal and gastric cancer.
Conclusion: Low intake of folate was associated with increased risk of esophageal squamous cell carcinoma.
C1 [Xiao, Q.; Freedman, N. D.; Abnet, C. C.; Park, Y.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Ren, J.] Natl Canc Ctr, Natl Off Canc Prevent & Control, Beijing, Peoples R China.
[Hollenbeck, A. R.] AARP, Washington, DC USA.
RP Xiao, Q (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
EM qian.xiao@nih.gov
RI Abnet, Christian/C-4111-2015; Freedman, Neal/B-9741-2015;
OI Abnet, Christian/0000-0002-3008-7843; Freedman,
Neal/0000-0003-0074-1098; Park, Yikyung/0000-0002-6281-489X
FU NIH, National Cancer Institute, Department of Health and Human Services;
Florida Department of Health, Tallahassee, Florida, USA
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Department of Health and Human Services.
Cancer incidence data from the Atlanta metropolitan area were collected
by the Georgia Center for Cancer Statistics, Department of Epidemiology,
Rollins School of Public Health, Emory University, Atlanta, Georgia,
USA. Cancer incidence data from California were collected by the
California Cancer Registry, California Department of Public Health's
Cancer Surveillance and Research Branch, Sacramento, California, USA.
Cancer incidence data from the Detroit metropolitan area were collected
by the Michigan Cancer Surveillance Program, Community Health
Administration, Lansing, Michigan, USA. The Florida cancer incidence
data used in this report were collected by the Florida Cancer Data
System (Miami, Florida, USA) under contract with the Florida Department
of Health, Tallahassee, Florida, USA. The views expressed herein are
solely those of the authors and do not necessarily reflect those of the
FCDC or FDOH. Cancer incidence data from Louisiana were collected by the
Louisiana Tumor Registry, Louisiana State University Health Sciences
Center School of Public Health, New Orleans, Louisiana, USA. Cancer
incidence data from New Jersey were collected by the New Jersey State
Cancer Registry, Cancer Epidemiology Services, New Jersey State
Department of Health, Trenton, New Jersey, USA. Cancer incidence data
from North Carolina were collected by the North Carolina Central Cancer
Registry, Raleigh, North Carolina, USA. Cancer incidence data from
Pennsylvania were supplied by the Division of Health Statistics and
Research, Pennsylvania Department of Health, Harrisburg, Pennsylvania,
USA. The Pennsylvania Department of Health specifically disclaims
responsibility for any analyses, interpretations, or conclusions. Cancer
incidence data from Arizona were collected by the Arizona Cancer
Registry, Division of Public Health Services, Arizona Department of
Health Services, Phoenix, Arizona, USA. Cancer incidence data from Texas
were collected by the Texas Cancer Registry, Cancer Epidemiology and
Surveillance Branch, Texas Department of State Health Services, Austin,
Texas, USA. Cancer incidence data from Nevada were collected by the
Nevada Central Cancer Registry, State Health Division, State of Nevada
Department of Health and Human Services, Las Vegas, Nevada, USA. We are
indebted to the participants in the NIH-AARP Diet and Health Study for
their outstanding cooperation. We also thank Sigurd Hermansen and Kerry
Grace Morrissey from Westat for study outcome ascertainment and
management and Leslie Carroll at Information Management Services for
data support and analysis. Guarantor of the article: XQ.
NR 25
TC 11
Z9 11
U1 1
U2 16
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
EI 1532-1827
J9 BRIT J CANCER
JI Br. J. Cancer
PD MAR 4
PY 2014
VL 110
IS 5
BP 1328
EP 1333
DI 10.1038/bjc.2014.17
PG 6
WC Oncology
SC Oncology
GA AC9EB
UT WOS:000332836000028
PM 24481406
ER
PT J
AU Jenkins, MR
Stinchcombe, JC
Au-Yeung, BB
Asano, Y
Ritter, AT
Weiss, A
Griffiths, GM
AF Jenkins, Misty R.
Stinchcombe, Jane C.
Au-Yeung, Byron B.
Asano, Yukako
Ritter, Alex T.
Weiss, Arthur
Griffiths, Gillian M.
TI Distinct structural and catalytic roles for Zap70 in formation of the
immunological synapse in CTL
SO ELIFE
LA English
DT Article
ID T-CELL-RECEPTOR; SEVERE COMBINED IMMUNODEFICIENCY; NATURAL-KILLER-CELLS;
MEDIATED CYTOTOXICITY; TYROSINE PHOSPHORYLATION; ACTIN POLYMERIZATION;
GRANULE POLARIZATION; SECRETORY GRANULES; RETROGRADE FLOW; ZAP-70 KINASE
AB T cell receptor (TCR) activation leads to a dramatic reorganisation of both membranes and receptors as the immunological synapse forms. Using a genetic model to rapidly inhibit Zap70 catalytic activity we examined synapse formation between cytotoxic T lymphocytes and their targets. In the absence of Zap70 catalytic activity Vav-1 activation occurs and synapse formation is arrested at a stage with actin and integrin rich interdigitations forming the interface between the two cells. The membranes at the synapse are unable to flatten to provide extended contact, and Lck does not cluster to form the central supramolecular activation cluster (cSMAC). Centrosome polarisation is initiated but aborts before reaching the synapse and the granules do not polarise. Our findings reveal distinct roles for Zap70 as a structural protein regulating integrin-mediated control of actin vs its catalytic activity that regulates TCR-mediated control of actin and membrane remodelling during formation of the immunological synapse.
C1 [Jenkins, Misty R.; Stinchcombe, Jane C.; Asano, Yukako; Ritter, Alex T.; Griffiths, Gillian M.] Univ Cambridge, Cambridge Inst Med Res, Cambridge, England.
[Au-Yeung, Byron B.; Weiss, Arthur] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Au-Yeung, Byron B.; Weiss, Arthur] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA.
[Ritter, Alex T.] NIH, Howard Hughes Med Inst, Bethesda, MD 20892 USA.
[Au-Yeung, Byron B.; Weiss, Arthur] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA USA.
RP Griffiths, GM (reprint author), Univ Cambridge, Cambridge Inst Med Res, Cambridge, England.
EM gg305@cam.ac.uk
OI Griffiths, Gillian/0000-0003-0434-5842; Au-Yeung,
Byron/0000-0002-6446-9102
FU Wellcome Trust [075880, 100140]; Howard Hughes Medical Institute;
Australian National Health and Medical Research Council (NHMRC)
Biomedical Fellowship [567082]; Arthritis Foundation [5476]; NIAMS,
National Institutes of Health [RC2AR058947]
FX Wellcome Trust 075880, 100140 Gillian M Griffiths; Howard Hughes Medical
Institute Arthur Weiss; Australian National Health and Medical Research
Council (NHMRC) Biomedical Fellowship 567082 Misty R Jenkins; Arthritis
Foundation 5476 Byron B Au-Yeung; NIAMS, National Institutes of Health
RC2AR058947 Arthur Weiss
NR 62
TC 11
Z9 11
U1 0
U2 9
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD MAR 4
PY 2014
VL 3
AR e01310
DI 10.7554/eLife.01310
PG 21
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA AC6IQ
UT WOS:000332625800001
PM 24596147
ER
PT J
AU de Koning, HJ
Meza, R
Plevritis, SK
ten Haaf, K
Munshi, VN
Jeon, J
Erdogan, SA
Kong, CY
Han, SS
van Rosmalen, J
Choi, SE
Pinsky, PF
de Gonzalez, AB
Berg, CD
Black, WC
Tammemagi, MC
Hazelton, WD
Feuer, EJ
McMahon, PM
AF de Koning, Harry J.
Meza, Rafael
Plevritis, Sylvia K.
ten Haaf, Kevin
Munshi, Vidit N.
Jeon, Jihyoun
Erdogan, Saadet Ayca
Kong, Chung Yin
Han, Summer S.
van Rosmalen, Joost
Choi, Sung Eun
Pinsky, Paul F.
de Gonzalez, Amy Berrington
Berg, Christine D.
Black, William C.
Tammemaegi, Martin C.
Hazelton, William D.
Feuer, Eric J.
McMahon, Pamela M.
TI Benefits and Harms of Computed Tomography Lung Cancer Screening
Strategies: A Comparative Modeling Study for the US Preventive Services
Task Force
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID LOW-DOSE CT; UNITED-STATES; SMOKING ABSTINENCE; SELECTION CRITERIA;
NELSON TRIAL; POPULATION; MORTALITY; PROSTATE; STAGE; RISK
AB Background: The optimum screening policy for lung cancer is unknown.
Objective: To identify efficient computed tomography (CT) screening scenarios in which relatively more lung cancer deaths are averted for fewer CT screening examinations.
Design: Comparative modeling study using 5 independent models.
Data Sources: The National Lung Screening Trial; the Prostate, Lung, Colorectal, and Ovarian Cancer Screening trial; the Surveillance, Epidemiology, and End Results program; and the U.S. Smoking History Generator.
Target Population: U.S. cohort born in 1950.
Time Horizon: Cohort followed from ages 45 to 90 years.
Perspective: Societal.
Intervention: 576 scenarios with varying eligibility criteria (age, pack-years of smoking, years since quitting) and screening intervals.
Outcome Measures: Benefits included lung cancer deaths averted or life-years gained. Harms included CT examinations, false-positive results (including those obtained from biopsy/surgery), overdiagnosed cases, and radiation-related deaths.
Results of Best-Case Scenario: The most advantageous strategy was annual screening from ages 55 through 80 years for ever-smokers with a smoking history of at least 30 pack-years and ex-smokers with less than 15 years since quitting. It would lead to 50% (model ranges, 45% to 54%) of cases of cancer being detected at an early stage (stage I/II), 575 screening examinations per lung cancer death averted, a 14% (range, 8.2% to 23.5%) reduction in lung cancer mortality, 497 lung cancer deaths averted, and 5250 life-years gained per the 100 000-member cohort. Harms would include 67 550 false-positive test results, 910 biopsies or surgeries for benign lesions, and 190 overdiagnosed cases of cancer (3.7% of all cases of lung cancer [model ranges, 1.4% to 8.3%]).
Results of Sensitivity Analysis: The number of cancer deaths averted for the scenario varied across models between 177 and 862; the number of overdiagnosed cases of cancer varied between 72 and 426.
Limitations: Scenarios assumed 100% screening adherence. Data derived from trials with short duration were extrapolated to lifetime follow-up.
Conclusion: Annual CT screening for lung cancer has a favorable benefit-harm ratio for individuals aged 55 through 80 years with 30 or more pack-years' exposure to smoking.
C1 Erasmus MC, NL-3000 CA Rotterdam, Netherlands.
Univ Michigan, Ann Arbor, MI 48109 USA.
Stanford Univ, Stanford, CA 94305 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
NCI, Bethesda, MD 20892 USA.
Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA.
Brock Univ, St Catharines, ON L2S 3A1, Canada.
RP de Koning, HJ (reprint author), Erasmus MC, Dept Publ Hlth, POB 2040, NL-3000 CA Rotterdam, Netherlands.
EM h.dekoning@erasmusmc.nl
RI Berg , Christine/K-1047-2014
FU National Cancer Institute
FX Primary Funding Source: National Cancer Institute.
NR 42
TC 120
Z9 121
U1 7
U2 24
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 MAR 4
PY 2014
VL 160
IS 5
BP 311
EP +
DI 10.7326/M13-2316
PG 15
WC Medicine, General & Internal
SC General & Internal Medicine
GA AC8OT
UT WOS:000332793900003
PM 24379002
ER
PT J
AU Kim, WC
Ma, CA
Li, WM
Chohan, M
Wilson, DM
Lee, CH
AF Kim, Wan Cheol
Ma, Conan
Li, Wai-Ming
Chohan, Manbir
Wilson, David M., III
Lee, Chow H.
TI Altered Endoribonuclease Activity of Apurinic/Apyrimidinic Endonuclease
1 Variants Identified in the Human Population
SO PLOS ONE
LA English
DT Article
ID AMYOTROPHIC-LATERAL-SCLEROSIS; EXCISION-REPAIR PATHWAY; DNA-REPAIR;
GENETIC POLYMORPHISMS; CANCER-RISK; BREAST-CANCER; MESSENGER-RNA; APE1;
APE1/REF-1; SITE
AB Apurinic/apyrimidinic endonuclease 1 (APE1) is the major mammalian enzyme in the DNA base excision repair pathway and cleaves the DNA phosphodiester backbone immediately 5' to abasic sites. APE1 also has 3'-5' DNA exonuclease and 3' DNA phosphodiesterase activities, and regulates transcription factor DNA binding through its redox regulatory function. The human APE1 has recently been shown to endonucleolytically cleave single-stranded regions of RNA. Towards understanding the biological significance of the endoribonuclease activity of APE1, we examined eight different amino acid substitution variants of APE1 previously identified in the human population. Our study shows that six APE1 variants, D148E, Q51H, I64V, G241R, R237A, and G306A, exhibit a 76-85% reduction in endoribonuclease activity against a specific coding region of the c-myc RNA, yet fully retain the ability to cleave apurinic/apyrimidinic DNA. We found that two APE1 variants, L104R and E126D, exhibit a unique RNase inhibitor-resistant endoribonuclease activity, where the proteins cleave c-myc RNA 3' of specific single-stranded guanosine residues. Expression of L104R and E126D APE1 variants in bacterial Origami cells leads to a 60-80% reduction in colony formation and a 1.5-fold increase in cell doubling time, whereas the other variants, which exhibit diminished endoribonuclease activity, had no effect. These data indicate that two human APE1 variants exhibit a unique endoribonuclease activity, which correlates with their ability to induce cytotoxicity or slow down growth in bacterial cells and supports the notion of their biological functionality.
C1 [Kim, Wan Cheol; Ma, Conan; Li, Wai-Ming; Chohan, Manbir; Lee, Chow H.] Univ British Columbia, Chem Program, Prince George, BC, Canada.
[Wilson, David M., III] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
RP Lee, CH (reprint author), Univ British Columbia, Chem Program, Prince George, BC, Canada.
EM chow.lee@unbc.ca
FU Natural Sciences & Engineering Research Council [227158]; Intramural
Research Program at the NIH, National Institute on Aging
FX This research was supported by a Discovery Grant (#227158) from Natural
Sciences & Engineering Research Council to CHL, and in part by the
Intramural Research Program at the NIH, National Institute on Aging to
DMWIII. The funders had no role in study design, decision to publish, or
preparation of the manuscript.
NR 22
TC 3
Z9 4
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 4
PY 2014
VL 9
IS 3
AR e90837
DI 10.1371/journal.pone.0090837
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC4FD
UT WOS:000332475500104
PM 24595156
ER
PT J
AU Afilalo, J
Alexander, KP
Mack, MJ
Maurer, MS
Green, P
Allen, LA
Popma, JJ
Ferrucci, L
Forman, DE
AF Afilalo, Jonathan
Alexander, Karen P.
Mack, Michael J.
Maurer, Mathew S.
Green, Philip
Allen, Larry A.
Popma, Jeffrey J.
Ferrucci, Luigi
Forman, Daniel E.
TI Frailty Assessment in the Cardiovascular Care of Older Adults
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE cardiovascular disease; elderly; frailty
ID PHYSICAL PERFORMANCE BATTERY; AORTIC-VALVE IMPLANTATION; LOWER-EXTREMITY
FUNCTION; AMERICAN-HEART-ASSOCIATION; IANA TASK-FORCE; GAIT SPEED;
CARDIAC-SURGERY; BODY-COMPOSITION; ELDERLY-PATIENTS; MUSCLE STRENGTH
C1 [Afilalo, Jonathan] McGill Univ, Jewish Gen Hosp, Div Cardiol, Montreal, PQ H3T 1E2, Canada.
[Afilalo, Jonathan] McGill Univ, Jewish Gen Hosp, Div Clin Epidemiol, Montreal, PQ H3T 1E2, Canada.
[Alexander, Karen P.] Duke Univ, Med Ctr, Div Cardiol, Durham, NC 27710 USA.
[Mack, Michael J.] Heart Hosp Baylor Plano, Div Cardiothorac Surg, Baylor Hlth Care Syst, Plano, TX USA.
[Maurer, Mathew S.; Green, Philip] Columbia Univ, Med Ctr, Div Cardiol, New York, NY USA.
[Allen, Larry A.] Univ Colorado, Sch Med, Div Cardiol, Aurora, CO USA.
[Popma, Jeffrey J.] Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA.
[Ferrucci, Luigi] NIA, NIH, Baltimore, MD 21224 USA.
[Forman, Daniel E.] Brigham & Womens Hosp, Div Cardiovasc Med, VA Boston Healthcare Ctr, Boston, MA 02115 USA.
RP Afilalo, J (reprint author), McGill Univ, Jewish Gen Hosp, Div Cardiol, 3755 Cote St Catherine Rd,E-222, Montreal, PQ H3T 1E2, Canada.
EM jonathan.afilalo@mcgill.ca
FU NHLBI NIH HHS [K23 HL121142]; NIA NIH HHS [L30 AG040558]
NR 110
TC 148
Z9 153
U1 10
U2 24
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 4
PY 2014
VL 63
IS 8
BP 747
EP 762
DI 10.1016/j.jacc.2013.09.070
PG 16
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AB3WM
UT WOS:000331720900002
PM 24291279
ER
PT J
AU Forbes, CE
Poore, JC
Krueger, F
Barbey, AK
Solomon, J
Grafman, J
AF Forbes, Chad E.
Poore, Joshua C.
Krueger, Frank
Barbey, Aron K.
Solomon, Jeffrey
Grafman, Jordan
TI The role of executive function and the dorsolateral prefrontal cortex in
the expression of neuroticism and conscientiousness
SO SOCIAL NEUROSCIENCE
LA English
DT Article
DE Personality; DLPC; Executive function; Neuroticism; Conscientiousness;
Self-control
ID GENERAL INTELLIGENCE; PERSONALITY-TRAITS; EMOTION REGULATION; BRAIN
VOLUME; EXTROVERSION; FMRI; METAANALYSIS; SOFTWARE; AMYGDALA; INJURY
AB The current study examined how specific neurological systems contribute to the expression of multiple personality dimensions. We used individuals with traumatic brain injuries to examine the contribution of the dorsolateral prefrontal cortex (DLPFC)a region important for executive function and attentionto the expression of neuroticism and conscientiousness factors and facets. Results from Voxel-Based Lesion-Symptom Mapping analyses revealed that focal damage to the left DLPFC (Brodmann's area 9) was associated with high neuroticism and low conscientious factor and facet scores (anxiety and self-discipline, respectively). Compared with lesioned and normal controls, veterans with damage in left DLPFC also reported higher neuroticism and lower conscientiousness facet scores, slower reaction times on the California Computerized Assessment Package assessment, and lower scores on the Delis-Kaplan executive function battery. Findings suggest that while neuroticism and conscientiousness remain psychometrically independent personality dimensions, their component facets may rely on a common neurocognitive infrastructure and executive function resources in general.
C1 [Forbes, Chad E.; Poore, Joshua C.; Krueger, Frank; Barbey, Aron K.; Solomon, Jeffrey; Grafman, Jordan] NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA.
[Forbes, Chad E.] Univ Delaware, Dept Psychol, Newark, DE 19716 USA.
[Forbes, Chad E.] Ctr Clin, Bethesda, MD USA.
[Forbes, Chad E.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA.
[Poore, Joshua C.] Charles Stark Draper Lab Inc, Boston, MA USA.
[Krueger, Frank] George Mason Univ, Dept Mol Neurosci, Fairfax, VA 22030 USA.
[Solomon, Jeffrey] Expert Image Anal LLC, Potomac, MD USA.
[Grafman, Jordan] Rehabil Inst Chicago, Chicago, IL 60611 USA.
[Grafman, Jordan] Northwestern Univ, Feinberg Sch Med, Alzheimers Dis Res Ctr, Dept Phys Med & Rehabil, Evanston, IL 60208 USA.
[Grafman, Jordan] Northwestern Univ, Feinberg Sch Med, Alzheimers Dis Res Ctr, Dept Psychiat & Behav Sci, Evanston, IL 60208 USA.
[Grafman, Jordan] Northwestern Univ, Feinberg Sch Med, Alzheimers Dis Res Ctr, Dept Cognit Neurol, Evanston, IL 60208 USA.
[Grafman, Jordan] Northwestern Univ, Dept Psychol, Evanston, IL 60208 USA.
RP Forbes, CE (reprint author), Univ Delaware, Dept Psychol, 111 Wolf Hall, Newark, DE 19716 USA.
EM cforbes@psych.udel.edu; jgrafman@northwestern.edu
RI Barbey, Aron/L-7312-2015;
OI Barbey, Aron/0000-0002-6092-0912; Grafman, Jordan H./0000-0001-8645-4457
FU Intramural Research Training Program of the National Institute of
Neurological Disorders and Stroke, National Institutes of Health; US
Army Medical Research and Material Command [DAMD17-01-1-0675]
FX This work was supported by the Intramural Research Training Program of
the National Institute of Neurological Disorders and Stroke, National
Institutes of Health, and a project grant from the US Army Medical
Research and Material Command administrated by the Henry M. Jackson
Foundation [Vietnam Head Injury Study Phase III: A 30-year post-injury
follow-up study: Grant number: DAMD17-01-1-0675]. The authors are
grateful to all the Vietnam veterans who participated in this study.
NR 52
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U1 3
U2 39
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND
SN 1747-0919
EI 1747-0927
J9 SOC NEUROSCI-UK
JI Soc. Neurosci.
PD MAR 4
PY 2014
VL 9
IS 2
BP 139
EP 151
DI 10.1080/17470919.2013.871333
PG 13
WC Neurosciences; Psychology
SC Neurosciences & Neurology; Psychology
GA AA2NZ
UT WOS:000330932600004
PM 24405294
ER
PT J
AU Hunt, MJO
Weissfeld, L
Boudreau, RM
Aizenstein, H
Newman, AB
Simonsick, EM
Van Domelen, DR
Thomas, F
Yaffe, K
Rosano, C
AF Hunt, Megan J. Olson
Weissfeld, Lisa
Boudreau, Robert M.
Aizenstein, Howard
Newman, Anne B.
Simonsick, Eleanor M.
Van Domelen, Dane R.
Thomas, Fridtjof
Yaffe, Kristine
Rosano, Caterina
TI A variant of sparse partial least squares for variable selection and
data exploration
SO FRONTIERS IN NEUROINFORMATICS
LA English
DT Article
DE high-dimensional; multicollinearity; over-fitting; SPLS; inference;
tuning parameters; network; MRI
ID FUNCTIONING OLDER-ADULTS; GRAY-MATTER ATROPHY; CARDIOVASCULAR HEALTH;
MR-IMAGES; BRAIN; REGRESSION; MEMORY; ABNORMALITIES; SEGMENTATION;
PREVALENCE
AB When data are sparse and/or predictors multicollinear, current implementation of sparse partial least squares (SPLS) does not give estimates for non-selected predictors nor provide a measure of inference. In response, an approach termed "all-possible" SPLS is proposed, which fits a SPLS model for all tuning parameter values across a set grid. Noted is the percentage of time a given predictor is chosen, as well as the average non-zero parameter estimate. Using a "large" number of multicollinear predictors, simulation confirmed variables not associated with the outcome were least likely to be chosen as sparsity increased across the grid of tuning parameters, while the opposite was true for those strongly associated. Lastly, variables with a weak association were chosen more often than those with no association, but less often than those with a strong relationship to the outcome. Similarly, predictors most strongly related to the outcome had the largest average parameter estimate magnitude, followed by those with a weak relationship, followed by those with no relationship. Across two independent studies regarding the relationship between volumetric MRI measures and a cognitive test score, this method confirmed a priori hypotheses about which brain regions would be selected most often and have the largest average parameter estimates. In conclusion, the percentage of time a predictor is chosen is a useful measure for ordering the strength of the relationship between the independent and dependent variables, serving as a form of inference. The average parameter estimates give further insight regarding the direction and strength of association. As a result, all-possible SPLS gives more information than the dichotomous output of traditional SPLS, making it useful when undertaking data exploration and hypothesis generation for a large number of potential predictors.
C1 [Hunt, Megan J. Olson; Weissfeld, Lisa] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15213 USA.
[Boudreau, Robert M.; Rosano, Caterina] Univ Pittsburgh, Ctr Aging & Populat Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA.
[Aizenstein, Howard] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA.
[Aizenstein, Howard] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15213 USA.
[Aizenstein, Howard] Univ Pittsburgh, Dept Clin & Translat Sci, Pittsburgh, PA 15213 USA.
[Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA.
[Simonsick, Eleanor M.] NIA, Intramural Res Program, Baltimore, MD 21224 USA.
[Van Domelen, Dane R.] Emory Univ, Dept Biostat, Atlanta, GA 30322 USA.
[Thomas, Fridtjof] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat Neurol & Epidemiol, San Francisco, CA 94143 USA.
RP Rosano, C (reprint author), Univ Pittsburgh, Ctr Aging & Populat Hlth, Dept Epidemiol, 130 N Bellefield St, Pittsburgh, PA 15213 USA.
EM rosanoc@edc.pitt.edu
RI Newman, Anne B./C-6408-2013;
OI Van Domelen, Dane/0000-0003-0051-7790; Newman, Anne
B./0000-0002-0106-1150; Rosano, Caterina/0000-0002-0909-1506; Rosano,
Caterina/0000-0002-4271-6010; Boudreau, Robert/0000-0003-0162-5187
FU National Institute on Aging (NIA) [AG-023629]; National Science
Foundation [DGE-0940903]; NIA [AG-023629, N01-AG-6-2103, N01-AG-6-2106,
NO1-AG-6-2101, R01-AG028050, AG-15928, AG-20098, AG-027058]; NINR
[R01-NR012459]; NIH, National Institute on Aging; National Heart, Lung,
and Blood Institute (NHLBI) [N01-HC-85239, N01-HC-85079, N01-HC-85086,
N01-HC-35129, N01-HC-15103, N01-HC-55222, N01-HC-75150, N01-HC-45133,
P30-AG-024827-01, HL080295]; National Institute of Neurological
Disorders and Stroke (NINDS); NHLBI [R01-HL-075366]; University of
Pittsburgh Claude D. Pepper Older Americans Independence Center
[P30-AG-024827-07]
FX This work was supported by the National Institute on Aging (NIA)
AG-023629 and the National Science Foundation Graduate Research
Fellowship DGE-0940903. Health ABC was supported by NIA contracts
N01-AG-6-2103, N01-AG-6-2106 and NO1-AG-6-2101; NIA grant R01-AG028050
and NINR grant R01-NR012459. This research was supported in part by the
Intramural Research Program of the NIH, National Institute on Aging. CHS
was supported by contract numbers N01-HC-85239, N01-HC-85079 through
N01-HC-85086, N01-HC-35129, N01-HC-15103, N01-HC-55222, N01-HC-75150,
N01-HC-45133, P30-AG-024827-01 and grant number HL080295 from the
National Heart, Lung, and Blood Institute (NHLBI), with added
contribution from the National Institute of Neurological Disorders and
Stroke (NINDS). Additional support was provided through AG-15928,
AG-20098, AG-027058 and AG-023629 from the NIA, R01-HL-075366 from the
NHLBI and the University of Pittsburgh Claude D. Pepper Older Americans
Independence Center P30-AG-024827-07. A full list of principal CHS
investigators and institutions can be found at https://chs-nhlbi.org/pi.
NR 41
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Z9 0
U1 1
U2 1
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1662-5196
J9 FRONT NEUROINFORM
JI Front. Neuroinformatics
PD MAR 3
PY 2014
VL 8
AR 18
DI 10.3389/fninf.2014.00018
PG 9
WC Mathematical & Computational Biology; Neurosciences
SC Mathematical & Computational Biology; Neurosciences & Neurology
GA AZ3CU
UT WOS:000348106200001
ER
PT J
AU Dal Monte, O
Noble, PL
Costa, VD
Averbeck, BB
AF Dal Monte, Olga
Noble, Pamela L.
Costa, Vincent D.
Averbeck, Bruno B.
TI Oxytocin enhances attention to the eye region in rhesus monkeys
SO FRONTIERS IN NEUROSCIENCE
LA English
DT Article
DE oxytocin; eyes; facial expression; free-viewing; gaze; eye tracking;
intranasal oxytocin; rhesus macaques
ID AUTISM SPECTRUM DISORDERS; INTRANASAL OXYTOCIN; EMOTIONAL FACES; FACIAL
EXPRESSIONS; AMYGDALA; HUMANS; GAZE; RECOGNITION; PATTERNS; MACAQUE
AB Human and non-human primates rely on the ability to perceive and interpret facial expressions to guide effective social interactions. The neuropeptide oxytocin (OT) has been shown to have a critical role in the perception of social cues, and in humans to increase the number of saccades to the eye region. To develop a useful primate model for the effects of OT on information processing, we investigated the influence of OT on gaze behavior during face processing in rhesus macaques. Forty-five minutes after a single intranasal dose of either 24IU OT or saline, monkeys completed a free-viewing task during which they viewed pictures of conspecifics displaying one of three facial expressions (neutral, open-mouth threat or bared-teeth) for 5s. The monkey was free to explore the face on the screen while the pattern of eye movements was recorded. OT did not increase overall fixations to the face compared to saline. Rather, when monkeys freely viewed conspecific faces, OT increased fixations to the eye region relative to the mouth region. This effect of OT was particularly pronounced when face position on the screen was manipulated so that the eye region was not the first facial feature seen by the monkeys. Together these findings are consistent with prior evidence in humans that intranasal administration of OT specifically enhances visual attention to the eye region compared to other informative facial features, thus validating the use of non-human primates to mechanistically explore how OT modulates social information processing and behavior.
C1 [Dal Monte, Olga; Noble, Pamela L.; Costa, Vincent D.; Averbeck, Bruno B.] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
[Dal Monte, Olga] Univ Turin, Dept Neuropsychol, Turin, Italy.
RP Averbeck, BB (reprint author), NIMH, Neuropsychol Lab, NIH, 49 Convent Dr MSC 4415, Bethesda, MD 20892 USA.
EM averbeckbb@mail.nih.gov
OI dal monte, olga/0000-0002-7823-4769; Costa, Vincent/0000-0002-5412-8945
FU National Institute of Health, NIMH
FX This research was supported by the Intramural Research Program of the
National Institute of Health, NIMH.
NR 55
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Z9 12
U1 4
U2 9
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1662-453X
J9 FRONT NEUROSCI-SWITZ
JI Front. Neurosci.
PD MAR 3
PY 2014
VL 8
AR 41
DI 10.3389/fnins.2014.00041
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA AW7FL
UT WOS:000346430000001
PM 24624055
ER
PT J
AU Riou, LM
Broisat, A
Ghezzi, C
Finet, G
Rioufol, G
Gharib, AM
Pettigrew, RI
Ohayon, J
AF Riou, Laurent M.
Broisat, Alexis
Ghezzi, Catherine
Finet, Gerard
Rioufol, Gilles
Gharib, Ahmed M.
Pettigrew, Roderic I.
Ohayon, Jacques
TI Effects of mechanical properties and atherosclerotic artery size on
biomechanical plaque disruption - Mouse vs. human
SO JOURNAL OF BIOMECHANICS
LA English
DT Article
DE Plaque disruption; Mouse; Human; Mechanical properties; Artery size
ID APOE-DEFICIENT MICE; E-KNOCKOUT MICE; MURINE MODELS; CIRCUMFERENTIAL
STRESS; CORONARY-ARTERIES; CAP THICKNESS; RUPTURE; LESIONS; BEHAVIOR;
AORTA
AB Mouse models of atherosclerosis are extensively being used to study the mechanisms of atherosclerotic plaque development and the results are frequently extrapolated to humans. However, major differences have been described between murine and human atherosclerotic lesions and the determination of similarities and differences between these species has been largely addressed recently. This study takes over and extends previous studies performed by our group and related to the biomechanical characterization of both mouse and human atherosclerotic lesions. Its main objective was to determine the distribution and amplitude of mechanical stresses including peak cap stress (PCS) in aortic vessels from atherosclerotic apoE(-/-) mice, in order to evaluate whether such biomechanical data would be in accordance with the previously suggested lack of plaque rupture in this model. Successful finite element analysis was performed from the zero-stress configuration of aortic arch sections and mainly indicated (1) the modest role of atherosclerotic lesions in the observed increase in residual parietal stresses in apoE(-/-) mouse vessels and (2) the low amplitude of murine PCS as compared to humans. Overall, the results from the present study support the hypothesis that murine biomechanical properties and artery size confer less propensity to rupture for mouse lesions in comparison with those of humans. (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Riou, Laurent M.; Broisat, Alexis; Ghezzi, Catherine] Fac Med Grenoble, Radiopharmaceut Bioclin, INSERM, UMR S 1039, Grenoble, France.
[Finet, Gerard; Rioufol, Gilles] Hosp Civils Lyon, Dept Hemodynam & Intervent Cardiol, Lyon, France.
[Finet, Gerard; Rioufol, Gilles] Univ Lyon 1, INSERM, U886, F-69365 Lyon, France.
[Gharib, Ahmed M.; Pettigrew, Roderic I.] NIDDK, Lab Integrat Cardiovasc Imaging Sci, NIH, Bethesda, MD 20892 USA.
[Pettigrew, Roderic I.; Ohayon, Jacques] UJF, CNRS, Lab TIMC IMAG DyCTiM, UMR 5525,In3S, Grenoble, France.
[Ohayon, Jacques] Univ Savoie, Polytech Annecy Chambery, Le Bourget Du Lac, France.
RP Pettigrew, RI (reprint author), UJF, CNRS, Lab TIMC IMAG DyCTiM, UMR 5525,In3S, Grenoble, France.
EM rpettig@mail.nih.gov; jacques.ohayon@imag.fr
RI Riou, Laurent/M-4562-2014; GHEZZI, Catherine/M-5185-2014; Ohayon,
Jacques/M-6576-2014; Gharib, Ahmed/O-2629-2016
OI Riou, Laurent/0000-0002-9240-4680; Gharib, Ahmed/0000-0002-2476-481X
FU Agence Nationale de la Recherche (ANR), France
FX Financial support was provided by the Agence Nationale de la Recherche
(ANR), France (ATHEBIOMECH 2007-2009 and MELANII 2009-2013 projects).
The authors thank Dr. Nicolas Mesnier (TIMC Laboratory, Grenoble,
France) for computational support, and Dr Alain Tedgui (Inserm U970,
Paris, France) for helpful discussions.
NR 47
TC 4
Z9 4
U1 0
U2 7
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0021-9290
EI 1873-2380
J9 J BIOMECH
JI J. Biomech.
PD MAR 3
PY 2014
VL 47
IS 4
SI SI
BP 765
EP 772
DI 10.1016/j.jbiomech.2014.01.020
PG 8
WC Biophysics; Engineering, Biomedical
SC Biophysics; Engineering
GA AE5BV
UT WOS:000334003700002
PM 24491495
ER
PT J
AU Chen, ZX
Golovnina, K
Sultana, H
Kumar, S
Oliver, B
AF Chen, Zhen-Xia
Golovnina, Kseniya
Sultana, Hina
Kumar, Satish
Oliver, Brian
TI Transcriptional effects of gene dose reduction
SO BIOLOGY OF SEX DIFFERENCES
LA English
DT Review
DE Sex; Monosomy; X chromosome; Dosage compensation; Buffering; Feedback;
Feed-forward; MSL complex
ID COPY NUMBER VARIATION; DROSOPHILA DOSAGE COMPENSATION; X-CHROMOSOME;
CAENORHABDITIS-ELEGANS; SEX-CHROMOSOMES; HUMAN GENOME; EXPRESSION;
MELANOGASTER; EVOLUTION; COMPLEX
AB Large-scale gene dose reductions usually lead to abnormal phenotypes or death. However, male mammals, Drosophila, and Caenorhabditis elegans have only one X chromosome and thus can be considered as monosomic for a major chromosome. Despite the deleterious effects brought about by such gene dose reduction in the case of an autosome, X chromosome monosomy in males is natural and innocuous. This is because of the nearly full transcriptional compensation for X chromosome genes in males, as opposed to no or partial transcriptional compensation for autosomal one-dose genes arising due to deletions. Buffering, the passive absorption of disturbance due to enzyme kinetics, and feedback responses triggered by expression change contribute to partial compensation. Feed-forward mechanisms, which are active responses to genes being located on the X, rather than actual gene dose are important contributors to full X chromosome compensation. In the last decade, highthroughput techniques have provided us with the tools to effectively and quantitatively measure the small-fold transcriptional effects of dose reduction. This is leading to a better understanding of compensatory mechanisms.
C1 [Chen, Zhen-Xia; Golovnina, Kseniya; Sultana, Hina; Kumar, Satish; Oliver, Brian] NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Chen, ZX (reprint author), NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA.
EM zhen-xia.chen@nih.gov
FU National Institutes of Health (NIDDK)
FX This work was supported by the Intramural Research Programs of the
National Institutes of Health (NIDDK).
NR 55
TC 4
Z9 4
U1 3
U2 9
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2042-6410
J9 BIOL SEX DIFFER
JI Biol. Sex Differ.
PD MAR 3
PY 2014
VL 5
AR 5
DI 10.1186/2042-6410-5-5
PG 7
WC Endocrinology & Metabolism; Genetics & Heredity
SC Endocrinology & Metabolism; Genetics & Heredity
GA AE0OC
UT WOS:000333664600001
PM 24581086
ER
PT J
AU Deshpande, RA
Williams, GJ
Limbo, O
Williams, RS
Kuhnlein, J
Lee, JH
Classen, S
Guenther, G
Russell, P
Tainer, JA
Paull, TT
AF Deshpande, Rajashree A.
Williams, Gareth J.
Limbo, Oliver
Williams, R. Scott
Kuhnlein, Jeff
Lee, Ji-Hoon
Classen, Scott
Guenther, Grant
Russell, Paul
Tainer, John A.
Paull, Tanya T.
TI ATP-driven Rad50 conformations regulate DNA tethering, end resection,
and ATM checkpoint signaling
SO EMBO JOURNAL
LA English
DT Article
DE DNA damage signaling; DNA repair; double-strand breaks; protein-DNA
interactions
ID DOUBLE-STRAND-BREAK; KINASE-ACTIVITY; MRE11/RAD50 COMPLEX;
CRYSTAL-STRUCTURE; FISSION YEAST; MRN COMPLEX; REPAIR; MRE11; BINDING;
RECOMBINATION
AB The Mre11-Rad50 complex is highly conserved, yet the mechanisms by which Rad50 ATP-driven states regulate the sensing, processing and signaling of DNA double-strand breaks are largely unknown. Here we design structure-based mutations in Pyrococcus furiosus Rad50 to alter protein core plasticity and residues undergoing ATP-driven movements within the catalytic domains. With this strategy we identify Rad50 separation-of-function mutants that either promote or destabilize the ATP-bound state. Crystal structures, X-ray scattering, biochemical assays, and functional analyses of mutant PfRad50 complexes show that the ATP-induced closed conformation promotes DNA end binding and end tethering, while hydrolysis-induced opening is essential for DNA resection. Reducing the stability of the ATP-bound state impairs DNA repair and Tel1 (ATM) checkpoint signaling in Schizosaccharomyces pombe, double-strand break resection in Saccharomyces cerevisiae, and ATM activation by human Mre11-Rad50-Nbs1 in vitro, supporting the generality of the P.furiosus Rad50 structure-based mutational analyses. These collective results suggest that ATP-dependent Rad50 conformations switch the Mre11-Rad50 complex between DNA tethering, ATM signaling, and 5 strand resection, revealing molecular mechanisms regulating responses to DNA double-strand breaks.
C1 [Deshpande, Rajashree A.; Kuhnlein, Jeff; Lee, Ji-Hoon; Paull, Tanya T.] Univ Texas Austin, Inst Cellular & Mol Biol, Howard Hughes Med Inst, Dept Mol Genet & Microbiol, Austin, TX 78712 USA.
[Williams, Gareth J.; Guenther, Grant; Tainer, John A.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA 94720 USA.
[Limbo, Oliver; Russell, Paul; Tainer, John A.] Scripps Res Inst, La Jolla, CA 92037 USA.
[Williams, R. Scott] NIEHS, Dept Hlth & Human Serv, Struct Biol Lab, US Natl Inst Hlth, Res Triangle Pk, NC 27709 USA.
[Classen, Scott] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Phys Biosci Div, Berkeley, CA 94720 USA.
[Tainer, John A.] Skaggs Inst Chem Biol, La Jolla, CA USA.
RP Paull, TT (reprint author), Univ Texas Austin, Inst Cellular & Mol Biol, Howard Hughes Med Inst, Dept Mol Genet & Microbiol, Austin, TX 78712 USA.
EM jat@scripps.edu; tpaull@mail.utexas.edu
RI Williams, Robert/A-6059-2015
FU NIH [CA094008, CA092584, CA117638, CA077325]; US National Institutes of
Health (NIH), National Institute of Environmental Health Sciences
(NIEHS) [1Z01ES102765-01]; United States Department of Energy program
Integrated Diffraction Analysis Technologies; NIH MINOS [R01GM105404]
FX We thank members of the Paull, Tainer, and Russell laboratories for
comments, Christophe Redon for the gamma H2A antibody, Antony Carr for
the TAP-Rad50 S. pombe strain, and Tom Wilson, Jim Haber, Sang Eun Lee,
and Tom Petes for S. cerevisiae strains. This study was supported by NIH
grants CA094008 to T.P., CA092584 to J.T. and T.P., CA117638 to J.T. and
P.R., CA077325 to P.R., and intramural research program of the US
National Institutes of Health (NIH), National Institute of Environmental
Health Sciences (NIEHS) (1Z01ES102765-01) to R.S.W. The SIBYLS beamline
(BL12.3.1) at the Advanced Light Source is supported by United States
Department of Energy program Integrated Diffraction Analysis
Technologies and NIH MINOS R01GM105404. Mass spectroscopy was performed
by the Protein and Metabolite Analysis Facility at UT Austin.
NR 55
TC 40
Z9 41
U1 0
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0261-4189
EI 1460-2075
J9 EMBO J
JI Embo J.
PD MAR 3
PY 2014
VL 33
IS 5
BP 482
EP 500
DI 10.1002/embj.201386100
PG 19
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AC3CC
UT WOS:000332391600010
PM 24493214
ER
PT J
AU Jha, A
Ahuja, M
Patel, S
Brailoiu, E
Muallem, S
AF Jha, Archana
Ahuja, Malini
Patel, Sandip
Brailoiu, Eugen
Muallem, Shmuel
TI Convergent regulation of the lysosomal two-pore channel-2 by Mg2+,
NAADP, PI(3,5) P2 and multiple protein kinases
SO EMBO JOURNAL
LA English
DT Article
DE channel; lysosome; Mg2+; NAADP; TPC2
ID ADENINE-DINUCLEOTIDE PHOSPHATE; MOBILIZES CALCIUM; ACIDIC ORGANELLES;
SENSITIVE CA2+; ION CHANNELS; RELEASE; TRAFFICKING; SIGNALS; CELLS; TPC2
AB Lysosomal Ca2+ homeostasis is implicated in disease and controls many lysosomal functions. A key in understanding lysosomal Ca2+ signaling was the discovery of the two-pore channels (TPCs) and their potential activation by NAADP. Recent work concluded that the TPCs function as a PI(3,5)P-2 activated channels regulated by mTORC1, but not by NAADP. Here, we identified Mg2+ and the MAPKs, JNK and P38 as novel regulators of TPC2. Cytoplasmic Mg2+ specifically inhibited TPC2 outward current, whereas lysosomal Mg2+ partially inhibited both outward and inward currents in a lysosomal lumen pH-dependent manner. Under controlled Mg2+, TPC2 is readily activated by NAADP with channel properties identical to those in response to PI(3,5)P-2. Moreover, TPC2 is robustly regulated by P38 and JNK. Notably, NAADP-mediated Ca2+ release in intact cells is regulated by Mg2+, PI(3,5)P-2, and P38/JNK kinases, thus paralleling regulation of TPC2 currents. Our data affirm a key role for TPC2 in NAADP-mediated Ca2+ signaling and link this pathway to Mg2+ homeostasis and MAP kinases, pointing to roles for lysosomal Ca2+ in cell growth, inflammation and cancer.
C1 [Jha, Archana; Ahuja, Malini; Muallem, Shmuel] NIDCR, Epithelial Signaling & Transport Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA.
[Patel, Sandip] UCL, Dept Cell & Dev Biol, London, England.
[Brailoiu, Eugen] Temple Univ, Sch Med, Dept Pharmacol, Philadelphia, PA 19122 USA.
RP Brailoiu, E (reprint author), Temple Univ, Sch Med, Dept Pharmacol, Philadelphia, PA 19122 USA.
EM ebrailou@temple.edu; shmuel.muallem@nih.gov
RI Patel, Sandip/O-9591-2015
OI Patel, Sandip/0000-0001-7247-2013
FU National Institutes of Health [HL090804]; NIH/NIDCR [DE000735-03]
FX This work was supported in part by National Institutes of Health Grants
HL090804 to E.B. and by NIH/NIDCR intramural grant DE000735-03 to S.M.
NR 50
TC 55
Z9 56
U1 2
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0261-4189
EI 1460-2075
J9 EMBO J
JI Embo J.
PD MAR 3
PY 2014
VL 33
IS 5
BP 501
EP 511
DI 10.1002/embj.201387035
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AC3CC
UT WOS:000332391600011
PM 24502975
ER
PT J
AU Robbins, HA
Li, Y
Porras, C
Pawlita, M
Ghosh, A
Rodriguez, AC
Schiffman, M
Wacholder, S
Kemp, TJ
Gonzalez, P
Schiller, J
Lowy, D
Esser, M
Matys, K
Quint, W
van Doorn, LJ
Herrero, R
Pinto, LA
Hildesheim, A
Waterboer, T
Safaeian, M
AF Robbins, Hilary A.
Li, Yan
Porras, Carolina
Pawlita, Michael
Ghosh, Arpita
Rodriguez, Ana Cecilia
Schiffman, Mark
Wacholder, Sholom
Kemp, Troy J.
Gonzalez, Paula
Schiller, John
Lowy, Douglas
Esser, Mark
Matys, Katie
Quint, Wim
van Doorn, Leen-Jan
Herrero, Rolando
Pinto, Ligia A.
Hildesheim, Allan
Waterboer, Tim
Safaeian, Mahboobeh
TI Glutathione S-transferase L1 multiplex serology as a measure of
cumulative infection with human papillomavirus
SO BMC INFECTIOUS DISEASES
LA English
DT Article
ID SQUAMOUS-CELL CARCINOMA; NEUTRALIZING EPITOPES; ANTIBODY-RESPONSES;
IMMUNE-RESPONSES; PARTICLE VACCINE; YOUNG-WOMEN; COSTA-RICA; ASSAY; HPV;
CANCER
AB Background: Several assays are used to measure type-specific serological responses to human papillomavirus (HPV), including the bead-based glutathione S-transferase (GST)-L1 multiplex serology assay and virus-like particle (VLP)-based ELISA. We evaluated the high-throughput GST-L1, which is increasingly used in epidemiologic research, as a measure of cumulative HPV infection and future immune protection among HPV-unvaccinated women.
Methods: We tested enrollment sera from participants in the control arm of the Costa Rica Vaccine Trial (n = 488) for HPV16 and HPV18 using GST-L1, VLP-ELISA, and two assays that measure neutralizing antibodies (cLIA and SEAP-NA). With statistical adjustment for sampling, we compared GST-L1 serostatus to established HPV seropositivity correlates and incident cervical HPV infection using odds ratios. We further compared GST-L1 to VLP-ELISA using pair-wise agreement statistics and by defining alternate assay cutoffs.
Results: Odds of HPV16 GST-L1 seropositivity increased with enrollment age (OR = 1.20 per year, 95% CI 1.03-1.40) and lifetime number of sexual partners (OR = 2.06 per partner, 95% CI 1.49-2.83), with similar results for HPV18. GST-L1 seropositivity did not indicate protection from incident infection over 4 years of follow-up (HPV16 adjusted OR = 1.72, 95% CI 0.95-3.13; HPV18 adjusted OR = 0.38, 95% CI 0.12-1.23). Seroprevalence by GST-L1 (HPV16 and HPV18, respectively) was 5.0% and 5.2%, compared to 19.4% and 23.8% by VLP-ELISA, giving positive agreement of 39.2% and 20.8%. Lowering GST-L1 seropositivity cutoffs improved GST-L1/VLP-ELISA positive agreement to 68.6% (HPV16) and 61.5% (HPV18).
Conclusions: Our data support GST-L1 as a marker of cumulative HPV infection, but not immune protection. At lower seropositivity cutoffs, GST-L1 better approximates VLP-ELISA.
C1 [Robbins, Hilary A.; Li, Yan; Schiffman, Mark; Wacholder, Sholom; Hildesheim, Allan; Safaeian, Mahboobeh] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Li, Yan] Univ Maryland, Joint Program Survey Methodol, College Pk, MD 20742 USA.
[Porras, Carolina; Rodriguez, Ana Cecilia; Gonzalez, Paula; Herrero, Rolando] Fdn INCIENSA, Proyecto Epidemiol Guanacaste, Guanacaste, Costa Rica.
[Pawlita, Michael; Waterboer, Tim] German Canc Res Ctr, Heidelberg, Germany.
[Ghosh, Arpita] Publ Hlth Fdn India, New Delhi, India.
[Kemp, Troy J.; Pinto, Ligia A.] SAIC Frederick Inc, Frederick Natl Lab Canc Res, HPV Immunol Lab, Frederick, MD USA.
[Gonzalez, Paula; Herrero, Rolando] Int Agcy Res Canc, F-69372 Lyon, France.
[Schiller, John; Lowy, Douglas] NCI, Ctr Canc Res, NIH, Rockville, MD USA.
[Esser, Mark] MedImmune, Gaithersburg, MD USA.
[Matys, Katie] PPD Vaccines & Biol Ctr Excellence, Wayne, PA USA.
[Quint, Wim; van Doorn, Leen-Jan] DDL Diagnost Lab, Rijswijk, Netherlands.
RP Robbins, HA (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
EM hilary.robbins@nih.gov
RI Hildesheim, Allan/B-9760-2015; Waterboer, Tim/G-1252-2010;
OI Hildesheim, Allan/0000-0003-0257-2363; Pawlita,
Michael/0000-0002-4720-8306
FU NCI [N01-CP-11005]; National Institutes of Health Office of Research on
Women's Health; Ministry of Health of Costa Rica
FX The Costa Rica HPV Vaccine Trial is a long-standing collaboration
between investigators in Costa Rica and the National Cancer Institute
(NCI). The trial is sponsored and funded by the NCI (contract
N01-CP-11005), with funding support from the National Institutes of
Health Office of Research on Women's Health, and done with support from
the Ministry of Health of Costa Rica. Vaccine was provided for our trial
by GlaxoSmithKline Biologicals, under a Clinical Trials Agreement with
the NCI. GlaxoSmithKline also provided support for aspects of the trial
associated with regulatory submission needs of the company under US Food
and Drug Administration BB-IND 7920. This study was designed, conducted,
and written by NCI investigators with input from investigators at
GlaxoSmithKline.
NR 44
TC 7
Z9 7
U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2334
J9 BMC INFECT DIS
JI BMC Infect. Dis.
PD MAR 3
PY 2014
VL 14
AR 120
DI 10.1186/1471-2334-14-120
PG 11
WC Infectious Diseases
SC Infectious Diseases
GA AC6KH
UT WOS:000332631000001
PM 24588945
ER
PT J
AU Mikawa, T
Maruyama, T
Okamoto, K
Nakagama, H
Lleonart, ME
Tsusaka, T
Hori, K
Murakami, I
Izumi, T
Takaori-Kondo, A
Yokode, M
Peters, G
Beach, D
Kondoh, H
AF Mikawa, Takumi
Maruyama, Takeshi
Okamoto, Koji
Nakagama, Hitoshi
Lleonart, Matilde E.
Tsusaka, Takeshi
Hori, Kousuke
Murakami, Itsuo
Izumi, Taisuke
Takaori-Kondo, Akifumi
Yokode, Masayuki
Peters, Gordon
Beach, David
Kondoh, Hiroshi
TI Senescence-inducing stress promotes proteolysis of phosphoglycerate
mutase via ubiquitin ligase Mdm2
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
ID ACTIVATED PROTEIN-KINASE; CELLULAR SENESCENCE; TUMOR SUPPRESSION;
ENOLASE ACTIVITY; P53 MUTATIONS; CANCER CELLS; LIFE-SPAN; IN-VIVO;
EXPRESSION; DEGRADATION
AB Despite the well-documented clinical significance of the Warburg effect, it remains unclear how the aggressive glycolytic rates of tumor cells might contribute to other hallmarks of cancer, such as bypass of senescence. Here, we report that, during oncogene- or DNA damage-induced senescence, Pak1 -mediated phosphorylation of phosphoglycerate mutase (PGAM) predisposes the glycolytic enzyme to ubiquitin-mediated degradation. We identify Mdm2 as a direct binding partner and ubiquitin ligase for PGAM in cultured cells and in vitro. Mutations in PGAM and Mdm2 that abrogate ubiquitination of PGAM restored the proliferative potential of primary cells under stress conditions and promoted neoplastic transformation. We propose that Mdm2, a downstream effector of p53, attenuates the Warburg effect via ubiquitination and degradation of PGAM.
C1 [Mikawa, Takumi; Maruyama, Takeshi; Tsusaka, Takeshi; Hori, Kousuke; Murakami, Itsuo; Kondoh, Hiroshi] Kyoto Univ, Grad Sch Med, Dept Geriatr Med, Kyoto 6068507, Japan.
[Takaori-Kondo, Akifumi] Kyoto Univ, Grad Sch Med, Dept Hematol Oncol, Kyoto 6068507, Japan.
[Okamoto, Koji; Nakagama, Hitoshi] Natl Canc Ctr, Res Inst, Div Canc Dev Syst, Tokyo 1040045, Japan.
[Lleonart, Matilde E.] Hosp Vall deHebron, Dept Pathol, Barcelona 08035, Spain.
[Izumi, Taisuke] NCI, Viral Mutat Sect, HIV Drug Resistance Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Yokode, Masayuki] Kyoto Univ Hosp, Translat Res Ctr, Dept Clin Innovat Med, Kyoto 6068507, Japan.
[Peters, Gordon] London Res Inst, Canc Res UK, London WC2A 3LY, England.
[Beach, David] Inst Cell & Mol Sci, Ctr Cutaneous Biol, London E1 2AT, England.
RP Kondoh, H (reprint author), Kyoto Univ, Grad Sch Med, Dept Geriatr Med, Kyoto 6068507, Japan.
EM hkondoh@kuhp.kyoto-u.ac.jp
RI Izumi, Taisuke/J-5607-2014
OI Izumi, Taisuke/0000-0002-9694-1459
FU Global COE program; Japan Society for the Promotion of Science; Ministry
of Education, Culture, Sports, Science, and Technology of Japan
[20590696, 23390186]; Japan Science and Technology Agency [8447, 5485];
Japan Science and Technology Agency (JST) Core Research for Evolutional
Science and Technology
FX T. Maruyama was supported by a postdoctoral fellowship from the Global
COE program "Center for Frontier Medicine." This work was supported in
part by grants from the Global COE program "Center for Frontier
Medicine," from the Japan Society for the Promotion of Science, from the
Ministry of Education, Culture, Sports, Science, and Technology of Japan
(grants No. 20590696 and No. 23390186), from the Japan Science and
Technology Agency (grants No. 8447 and No. 5485), and from Japan Science
and Technology Agency (JST) Core Research for Evolutional Science and
Technology (CREST No. 18 to H. Kondoh).
NR 61
TC 12
Z9 13
U1 0
U2 6
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0021-9525
EI 1540-8140
J9 J CELL BIOL
JI J. Cell Biol.
PD MAR 3
PY 2014
VL 204
IS 5
BP 729
EP 745
DI 10.1083/jcb.201306149
PG 17
WC Cell Biology
SC Cell Biology
GA AC3OC
UT WOS:000332430100011
PM 24567357
ER
PT J
AU Jeff, JM
Armstrong, LL
Ritchie, MD
Denny, JC
Kho, AN
Basford, MA
Wolf, WA
Pacheco, JA
Li, RL
Chisholm, RL
Roden, DM
Hayes, MG
Crawford, DC
AF Jeff, Janina M.
Armstrong, Loren L.
Ritchie, Marylyn D.
Denny, Joshua C.
Kho, Abel N.
Basford, Melissa A.
Wolf, Wendy A.
Pacheco, Jennifer A.
Li, Rongling
Chisholm, Rex L.
Roden, Dan M.
Hayes, M. Geoffrey
Crawford, Dana C.
TI Admixture Mapping and Subsequent Fine-Mapping Suggests a Biologically
Relevant and Novel Association on Chromosome 11 for Type 2 Diabetes in
African Americans
SO PLOS ONE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; ELECTRONIC MEDICAL-RECORDS; EMERGE NETWORK;
RISK LOCI; SUSCEPTIBILITY; VARIANT; VISUALIZATION; METAANALYSIS;
ANCESTRY; GENETICS
AB Type 2 diabetes (T2D) is a complex metabolic disease that disproportionately affects African Americans. Genome-wide association studies (GWAS) have identified several loci that contribute to T2D in European Americans, but few studies have been performed in admixed populations. We first performed a GWAS of 1,563 African Americans from the Vanderbilt Genome-Electronic Records Project and Northwestern University NUgene Project as part of the electronic Medical Records and Genomics (eMERGE) network. We successfully replicate an association in TCF7L2, previously identified by GWAS in this African American dataset. We were unable to identify novel associations at p<5.0x10(-8) by GWAS. Using admixture mapping as an alternative method for discovery, we performed a genome-wide admixture scan that suggests multiple candidate genes associated with T2D. One finding, TCIRG1, is a T-cell immune regulator expressed in the pancreas and liver that has not been previously implicated for T2D. We performed subsequent fine-mapping to further assess the association between TCIRG1 and T2D in >5,000 African Americans. We identified 13 independent associations between TCIRG1, CHKA, and ALDH3B1 genes on chromosome 11 and T2D. Our results suggest a novel region on chromosome 11 identified by admixture mapping is associated with T2D in African Americans.
C1 [Jeff, Janina M.] Vanderbilt Univ, Charles Bronfman Inst Personalized Med, Icahn Sch Med Mt Sinai, Nashville, TN 37235 USA.
[Crawford, Dana C.] Vanderbilt Univ, Ctr Human Genet Res, Nashville, TN 37235 USA.
[Denny, Joshua C.; Roden, Dan M.] Vanderbilt Univ, Dept Med, Div Clin Pharmacol, Nashville, TN 37235 USA.
[Denny, Joshua C.] Vanderbilt Univ, Dept Biomed Informat, Nashville, TN 37235 USA.
[Basford, Melissa A.; Roden, Dan M.] Vanderbilt Univ, Off Personalized Med, Nashville, TN 37235 USA.
[Roden, Dan M.] Vanderbilt Univ, Dept Pharmacol, Nashville, TN 37235 USA.
[Kho, Abel N.] Northwestern Univ, Div Gen Internal Med, Feinberg Sch Med, Chicago, IL 60611 USA.
[Armstrong, Loren L.; Hayes, M. Geoffrey] Northwestern Univ, Div Endocrinol Metab & Mol Med, Feinberg Sch Med, Chicago, IL 60611 USA.
[Pacheco, Jennifer A.; Chisholm, Rex L.; Hayes, M. Geoffrey] Northwestern Univ, Ctr Genet Med, Feinberg Sch Med, Chicago, IL 60611 USA.
[Wolf, Wendy A.] Childrens Hosp, Div Genet, Boston, MA 02115 USA.
[Li, Rongling] NHGRI, Off Populat Genom, Bethesda, MD 20892 USA.
[Ritchie, Marylyn D.] Penn State Univ, Dept Biochem & Mol Biol, Ctr Syst Genom, University Pk, PA 16802 USA.
RP Crawford, DC (reprint author), Vanderbilt Univ, Ctr Human Genet Res, 221 Kirkland Hall, Nashville, TN 37235 USA.
EM crawford@chgr.mc.vanderbilt.edu
FU NIH/NHGRI [U01HG004609, U01HG04603]; NCATS/NIH [UL1 TR000445]
FX This work was supported by NIH/NHGRI U01HG004609 (Northwestern
University as part of eMERGE) and U01HG04603 (Vanderbilt University as
part of eMERGE, also serving as the Administrative Coordinating Center).
A portion of the dataset(s) used for the analyses described were
obtained from Vanderbilt University Medical Center's BioVU which is
supported by institutional funding and by the Vanderbilt CTSA grant UL1
TR000445 from NCATS/NIH. As part of the cooperative agreement, NHGRI
participated in the study design, data collection and analysis, and
preparation of the manuscript.
NR 54
TC 6
Z9 6
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 3
PY 2014
VL 9
IS 3
AR e86931
DI 10.1371/journal.pone.0086931
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC4CT
UT WOS:000332468900001
PM 24595071
ER
PT J
AU Fliedner, S
Engel, T
Lendvai, N
Shankavaram, U
Nolting, S
Wesley, R
Elkalouhn, A
Ungefroren, H
Lehnert, H
Timmers, H
Pacak, K
AF Fliedner, S.
Engel, T.
Lendvai, N.
Shankavaram, U.
Noelting, S.
Wesley, R.
Elkalouhn, A.
Ungefroren, H.
Lehnert, H.
Timmers, H.
Pacak, K.
TI Anti-cancer potential of MAPK pathway inhibition in paragangliomas -
effect of different statins on mouse pheochromocytoma cells
SO EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES
LA English
DT Meeting Abstract
C1 [Fliedner, S.; Engel, T.; Lendvai, N.; Noelting, S.; Pacak, K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Med Neuroendocrinol, Bethesda, MD USA.
[Fliedner, S.; Ungefroren, H.; Lehnert, H.] Univ Med Ctr Schleswig Holstein, Dept Med 1, Lubeck, Germany.
[Engel, T.; Timmers, H.] Radboud Univ Nijmegen, Med Ctr, Dept Endocrinol, NL-6525 ED Nijmegen, Netherlands.
[Shankavaram, U.] NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA.
[Noelting, S.] Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med, Dept Endocrinol, London, England.
[Noelting, S.] Queen Mary Univ London, Barts Canc Inst, Barts & London Sch Med, Dept Endocrinol, London, England.
[Wesley, R.] NIH, Warren G Magnuseon Clin Ctr, Bethesda, MD 20892 USA.
[Elkalouhn, A.] NHGRI, Canc Genet Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JOHANN AMBROSIUS BARTH VERLAG MEDIZINVERLAGE HEIDELBERG GMBH
PI STUTTGART
PA RUEDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0947-7349
EI 1439-3646
J9 EXP CLIN ENDOCR DIAB
JI Exp. Clin. Endocrinol. Diabet.
PD MAR
PY 2014
VL 122
IS 3
MA OP6_29
DI 10.1055/s-0034-1372004
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AY2FF
UT WOS:000347403300051
ER
PT J
AU Richter, S
Peitzsch, M
Rapizzi, E
Lenders, JW
Qin, N
de Cubas, AA
Schiavi, F
Rao, JU
Beuschlein, F
Quinkler, M
Timmers, HJ
Opocher, G
Mannelli, M
Pacak, K
Robledo, M
Eisenhofer, G
AF Richter, S.
Peitzsch, M.
Rapizzi, E.
Lenders, J. W.
Qin, N.
de Cubas, A. A.
Schiavi, F.
Rao, J. U.
Beuschlein, F.
Quinkler, M.
Timmers, H. J.
Opocher, G.
Mannelli, M.
Pacak, K.
Robledo, M.
Eisenhofer, G.
TI Identification and stratification of pheochromocytomas/paragangliomas
with SDHx mutations using the succinate to fumarate ratio
SO EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES
LA English
DT Meeting Abstract
C1 [Richter, S.; Peitzsch, M.; Qin, N.; Eisenhofer, G.] Tech Univ Dresden, Univ Hosp Dresden, Dept Clin Chem & Lab Med, Dresden, Germany.
[Rapizzi, E.; Mannelli, M.] Univ Florence, Ist Toscano Tumori, Dept Clin Pathophysiol, Florence, Italy.
[Lenders, J. W.; Rao, J. U.; Timmers, H. J.] Radboud Univ Nijmegen, Med Ctr, Dept Med, NL-6525 ED Nijmegen, Netherlands.
[Lenders, J. W.; Eisenhofer, G.] Tech Univ Dresden, Univ Hosp Dresden, Dept Med 3, Dresden, Germany.
[de Cubas, A. A.; Robledo, M.] CNIO Madrid, Hereditary Endocrine Canc Grp, Madrid, Spain.
[Schiavi, F.; Opocher, G.] Veneto Inst Oncol IRCCS Padova, Padua, Italy.
[Beuschlein, F.] Univ Munich, Med Klin & Poliklin 4, Munich, Germany.
[Quinkler, M.] Univ Hosp Charite Berlin, Berlin, Germany.
[Pacak, K.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU JOHANN AMBROSIUS BARTH VERLAG MEDIZINVERLAGE HEIDELBERG GMBH
PI STUTTGART
PA RUEDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0947-7349
EI 1439-3646
J9 EXP CLIN ENDOCR DIAB
JI Exp. Clin. Endocrinol. Diabet.
PD MAR
PY 2014
VL 122
IS 3
MA OP6_30
DI 10.1055/s-0034-1372005
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AY2FF
UT WOS:000347403300052
ER
PT J
AU Sue, M
Martucci, V
Frey, F
Lenders, JWM
Timmers, H
Peczkowska, M
Robledo, M
Pacak, K
Eisenhofer, G
AF Sue, M.
Martucci, V.
Frey, F.
Lenders, J. W. M.
Timmers, H.
Peczkowska, M.
Robledo, M.
Pacak, K.
Eisenhofer, G.
TI SDHB mutation testing in metastatic pheochromocytoma and paraganglioma:
Is this required in patients with adrenaline-producing tumors?
SO EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES
LA English
DT Meeting Abstract
C1 [Sue, M.; Eisenhofer, G.] Univ Dresden, Dept Med 3, Dresden, Germany.
[Martucci, V.; Pacak, K.] NIH, Bethesda, MD 20892 USA.
[Frey, F.; Eisenhofer, G.] Univ Dresden, Inst Clin Chem & Lab Med, Dresden, Germany.
[Lenders, J. W. M.; Timmers, H.] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, NL-6525 ED Nijmegen, Netherlands.
[Peczkowska, M.] Inst Cardiol, Dept Hypertent, Warsaw, Poland.
[Robledo, M.] Spanish Natl Canc Res Ctr Med, Hereditary Endocrine Canc Grp, Madrid, Spain.
RI Lenders, J.W.M./L-4487-2015
NR 0
TC 0
Z9 0
U1 0
U2 2
PU JOHANN AMBROSIUS BARTH VERLAG MEDIZINVERLAGE HEIDELBERG GMBH
PI STUTTGART
PA RUEDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0947-7349
EI 1439-3646
J9 EXP CLIN ENDOCR DIAB
JI Exp. Clin. Endocrinol. Diabet.
PD MAR
PY 2014
VL 122
IS 3
MA P111
DI 10.1055/s-0034-1372128
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AY2FF
UT WOS:000347403300172
ER
PT J
AU Parisiadou, L
Yu, J
Sgobio, C
Xie, CS
Liu, GX
Sun, LX
Gu, XL
Lin, X
Crowley, NA
Lovinger, DM
Cai, HB
AF Parisiadou, Loukia
Yu, Jia
Sgobio, Carmelo
Xie, Chengsong
Liu, Guoxiang
Sun, Lixin
Gu, Xing-Long
Lin, Xian
Crowley, Nicole A.
Lovinger, David M.
Cai, Huaibin
TI LRRK2 regulates synaptogenesis and dopamine receptor activation through
modulation of PKA activity
SO NATURE NEUROSCIENCE
LA English
DT Article
ID PROTEIN-KINASE-A; DENDRITIC SPINE MORPHOGENESIS; AKAP SIGNALING
COMPLEXES; PARKINSONS-DISEASE; SYNAPTIC PLASTICITY; POSTSYNAPTIC
DENSITY; ROC DOMAIN; CYCLIC-AMP; PHOSPHORYLATION; MICE
AB Leucine-rich repeat kinase 2 (LRRK2) is enriched in the striatal projection neurons (SPNs). We found that LRRK2 negatively regulates protein kinase A (PKA) activity in the SPNs during synaptogenesis and in response to dopamine receptor Drd1 activation. LRRK2 interacted with PKA regulatory subunit II beta (PKARII beta). A lack of LRRK2 promoted the synaptic translocation of PKA and increased PKA-mediated phosphorylation of actin-disassembling enzyme cofilin and glutamate receptor GluR1, resulting in abnormal synaptogenesis and transmission in the developing SPNs. Furthermore, PKA-dependent phosphorylation of GluR1 was also aberrantly enhanced in the striatum of young and aged Lrrk2(-/-) mice after treatment with a Drd1 agonist. Notably, a Parkinson's disease-related Lrrk2 R1441C missense mutation that impaired the interaction of LRRK2 with PKARIIb also induced excessive PKA activity in the SPNs. Our findings reveal a previously unknown regulatory role for LRRK2 in PKA signaling and suggest a pathogenic mechanism of SPN dysfunction in Parkinson's disease.
C1 [Parisiadou, Loukia; Yu, Jia; Sgobio, Carmelo; Xie, Chengsong; Liu, Guoxiang; Sun, Lixin; Gu, Xing-Long; Lin, Xian; Cai, Huaibin] NIA, Transgen Sect, Neurogenet Lab, US NIH, Bethesda, MD 20892 USA.
[Parisiadou, Loukia; Liu, Guoxiang] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Yu, Jia] Beijing Geriatr Hosp, Dept Geriatr, Beijing, Peoples R China.
[Crowley, Nicole A.; Lovinger, David M.] NIAAA, Lab Integrat Neurosci, US NIH, Rockville, MD 20852 USA.
RP Cai, HB (reprint author), NIA, Transgen Sect, Neurogenet Lab, US NIH, Bethesda, MD 20892 USA.
EM loukia.parisiadou@northwestern.edu; caih@mail.nih.gov
RI Yu, Jia/J-2792-2014; gu, xinglong/A-3054-2011
OI gu, xinglong/0000-0002-0437-5606
FU National Institute on Aging [AG000944, AG000928]; National Institute of
Alcohol Abuse and Alcoholism
FX We thank H. Zhong (Vollum Institute) for providing PKA expression
vectors, M. Cookson (National Institute on Aging) for providing human
Lrrk2 expression vector, J. Shen and Y. Tong (Harvard University) for
providing Lrrk2 R1441C knock-in mice, P. Lewis (University College
London) for providing LRRK2 wild-type and R1441C recombinant proteins,
and V. Alvarez (National Institute of Alcohol Abuse and Alcoholism), B.
Ma (National Institute on Aging) and Z. Li, J.-M. Jia and S. Jiao
(National Institute of Mental Health) for their advice and technical
support. We also thank L. Donahue and N. Sastry for their assistance in
editing the manuscript. This work was supported by the intramural
research programs of National Institute on Aging (AG000944 and AG000928
to H. C.) and National Institute of Alcohol Abuse and Alcoholism (D.L.).
NR 59
TC 45
Z9 46
U1 0
U2 8
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
EI 1546-1726
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD MAR
PY 2014
VL 17
IS 3
BP 367
EP 376
DI 10.1038/nn.3636
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA AB8CA
UT WOS:000332016500009
PM 24464040
ER
PT J
AU Jin, X
Tecuapetla, F
Costa, RM
AF Jin, Xin
Tecuapetla, Fatuel
Costa, Rui M.
TI Basal ganglia subcircuits distinctively encode the parsing and
concatenation of action sequences
SO NATURE NEUROSCIENCE
LA English
DT Article
ID DIFFERENTIAL ROLES; FOREBRAIN CIRCUIT; SUBSTANTIA-NIGRA;
GLOBUS-PALLIDUS; EYE-MOVEMENTS; NEURONS; INFORMATION; CHUNKING; DISEASE;
SPEECH
AB Chunking allows the brain to efficiently organize memories and actions. Although basal ganglia circuits have been implicated in action chunking, little is known about how individual elements are concatenated into a behavioral sequence at the neural level. Using a task in which mice learned rapid action sequences, we uncovered neuronal activity encoding entire sequences as single actions in basal ganglia circuits. In addition to neurons with activity related to the start/stop activity signaling sequence parsing, we found neurons displaying inhibited or sustained activity throughout the execution of an entire sequence. This sustained activity covaried with the rate of execution of individual sequence elements, consistent with motor concatenation. Direct and indirect pathways of basal ganglia were concomitantly active during sequence initiation, but behaved differently during sequence performance, revealing a more complex functional organization of these circuits than previously postulated. These results have important implications for understanding the functional organization of basal ganglia during the learning and execution of action sequences.
C1 [Jin, Xin; Costa, Rui M.] NIAAA, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA.
[Jin, Xin] Salk Inst Biol Studies, Mol Neurobiol Lab, La Jolla, CA 92037 USA.
[Tecuapetla, Fatuel; Costa, Rui M.] Inst Gulbenkian Ciencias, Champalimaud Neurosci Programme, Lisbon, Portugal.
[Tecuapetla, Fatuel; Costa, Rui M.] Champalimaud Ctr Unknown, Lisbon, Portugal.
RP Jin, X (reprint author), NIAAA, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA.
EM xjin@salk.edu; rui.costa@neuro.fchampalimaud.org
OI Tecuapetla, Fatuel/0000-0002-9191-6553; Costa, Rui/0000-0003-0495-8374
FU National Institute on Alcohol Abuse and Alcoholism Division of
Intramural Clinical and Biological Research; Champalimaud Neuroscience
Programme, European Research Council [243393]; Howard Hughes Medical
Institute International Early Careers Scientist Grant; Whitehall
Foundation; US National Institutes of Health [NS083815]
FX We thank C. Gerfen for the D1-Cre and D2-Cre mice (US National
Institutes of Health), Y. Li for the Rgs9-cre mice (University of
Florida), K. Nakazawa for the Grin1loxP/loxP mice (US
National Institutes of Health), G. Luo and A. Vaz for genotyping, and G.
Cui for comments on the manuscript. This research was supported by the
National Institute on Alcohol Abuse and Alcoholism Division of
Intramural Clinical and Biological Research, the Champalimaud
Neuroscience Programme, European Research Council grant 243393 and
Howard Hughes Medical Institute International Early Careers Scientist
Grant to R. M. C., the Whitehall Foundation, and US National Institutes
of Health grant NS083815 to X.J.
NR 50
TC 80
Z9 80
U1 5
U2 24
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
EI 1546-1726
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD MAR
PY 2014
VL 17
IS 3
BP 423
EP 430
DI 10.1038/nn.3632
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA AB8CA
UT WOS:000332016500016
PM 24464039
ER
PT J
AU Raj, P
Hohenadel, K
Demers, PA
Zahm, SH
Blair, A
AF Raj, Priyanka
Hohenadel, Karin
Demers, Paul A.
Zahm, Shelia Hoar
Blair, Aaron
TI Recent Trends in Published Occupational Cancer Epidemiology Research:
Results from a Comprehensive Review of the Literature
SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE
LA English
DT Review
DE occupational; epidemiology; literature review; dose-response; cancer
ID EXPOSURE; COUNTRIES; WORKERS
AB Objective To assess trends in occupational cancer epidemiology research through a literature review of occupational health and epidemiology journals.
Methods Fifteen journals were reviewed from 1991 to 2009, and characteristics of articles that assessed the risk of cancer associated with an occupation, industry, or occupational exposure, were incorporated into a database.
Results The number of occupational cancer epidemiology articles published annually declined in recent years (2003 onwards) in the journals reviewed. The number of articles presenting dose-response analyses increased over the review period, from 29% in the first 4 years of review to 49% in the last 4 years.
Conclusion There has been a decrease in the number of occupational cancer epidemiology articles published annually during the review period. The results of these articles help determine the carcinogenicity of workplace exposures and permissible exposure limits, both of which may be hindered with a decline in research. (C) 2013 Wiley Periodicals, Inc.
C1 [Raj, Priyanka; Hohenadel, Karin; Demers, Paul A.; Blair, Aaron] Occupat Canc Res Ctr, Toronto, ON, Canada.
[Demers, Paul A.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.
[Zahm, Shelia Hoar] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Raj, P (reprint author), 505 Univ Ave,Seventeenth Floor, Toronto, ON M5G 1X3, Canada.
EM priyanka.raj@occupationalcancer.ca
RI Zahm, Shelia/B-5025-2015
NR 17
TC 2
Z9 2
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0271-3586
EI 1097-0274
J9 AM J IND MED
JI Am. J. Ind. Med.
PD MAR
PY 2014
VL 57
IS 3
BP 259
EP 264
DI 10.1002/ajim.22280
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AX0SE
UT WOS:000346661300001
PM 24488816
ER
PT J
AU Gupta, S
Tatouli, IP
Rosen, LB
Hasni, S
Siegel, RM
Holland, SM
Moutsopopoulos, HM
Browne, SK
AF Gupta, Sarthak
Tatouli, Ioanna P.
Rosen, Lindsey B.
Hasni, Sarfaraz
Siegel, Richard M.
Holland, Steven M.
Moutsopopoulos, Haralampos M.
Browne, Sarah K.
TI RHEUMATOID ARTHRITIS, SJOGREN'S SYNDROME AND SYSTEMIC LUPUS
ERYTHEMATOSUS PATIENTS HAVE A DISTINCT SPECTRUM OF SERUM ANTICYTOKINE
AUTOANTIBODIES
SO ANNALS OF THE RHEUMATIC DISEASES
LA English
DT Meeting Abstract
CT European Workshop for Rheumatology Research
CY FEB 20-22, 2014
CL Lisbon, PORTUGAL
C1 [Gupta, Sarthak; Hasni, Sarfaraz; Siegel, Richard M.] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Gupta, Sarthak; Rosen, Lindsey B.; Holland, Steven M.; Browne, Sarah K.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Tatouli, Ioanna P.; Moutsopopoulos, Haralampos M.] Natl Tech Univ Athens, Sch Med, GR-10682 Athens, Greece.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0003-4967
EI 1468-2060
J9 ANN RHEUM DIS
JI Ann. Rheum. Dis.
PD MAR
PY 2014
VL 73
SU 1
MA A3.31
BP A54
EP A55
DI 10.1136/annrheumdis-2013-205124.124
PG 6
WC Rheumatology
SC Rheumatology
GA AW4JW
UT WOS:000346248400125
ER
PT J
AU Roth, JC
Cassady, KA
Cody, JJ
Parker, JN
Price, KH
Coleman, JM
Peggins, JO
Noker, PE
Powers, NW
Grimes, SD
Carroll, SL
Gillespie, GY
Whitley, RJ
Markert, JM
AF Roth, Justin C.
Cassady, Kevin A.
Cody, James J.
Parker, Jackie N.
Price, Kathleen H.
Coleman, Jennifer M.
Peggins, James O.
Noker, Patricia E.
Powers, Nicholas W.
Grimes, Sheila D.
Carroll, Steven L.
Gillespie, G. Yancey
Whitley, Richard J.
Markert, James M.
TI Evaluation of the Safety and Biodistribution of M032, an Attenuated
Herpes Simplex Virus Type 1 Expressing hIL-12, After Intracerebral
Administration to Aotus Nonhuman Primates
SO HUMAN GENE THERAPY CLINICAL DEVELOPMENT
LA English
DT Article
ID HUMAN-MALIGNANT GLIOMA; BRAIN-TUMORS; GAMMA(1)34.5 PROTEIN;
EXPERIMENTAL-THERAPY; CYTOSINE DEAMINASE; ONCOLYTIC VIRUS; OWL MONKEY;
IFN-GAMMA; IN-VIVO; MUTANT
AB Herpes simplex virus type 1 (HSV-1) mutants lacking the gamma(1)34.5 neurovirulence loci are promising agents for treating malignant glioma. Arming oncolytic HSV-1 to express immunostimulatory genes may potentiate therapeutic efficacy. We have previously demonstrated improved preclinical efficacy, biodistribution, and safety of M002, a gamma(1)34.5-deleted HSV-1 engineered to express murine IL-12. Herein, we describe the safety and biodistribution of M032, a gamma(1)34.5-deleted HSV-1 virus that expresses human IL-12 after intracerebral administration to nonhuman primates, Aotus nancymae. Cohorts were administered vehicle, 10(6), or 10(8) pfu of M032 on day 1 and subjected to detailed clinical observations performed serially over a 92-day trial. Animals were sacrificed on days 3, 31, and 91 for detailed histopathologic assessments of all organs and to isolate and quantify virus in all organs. With the possible exception of one animal euthanized on day 16, neither adverse clinical signs nor sex- or dose-related differences were attributed to M032. Elevated white blood cell and neutrophil counts were observed in virus-injected groups on day 3, but no other significant changes were noted in clinical chemistry or coagulation parameters. Minimal to mild inflammation and fibrosis detected, primarily in meningeal tissues, in M032-injected animals on days 3 and 31 had mostly resolved by day 91. The highest viral DNA levels were detected at the injection site and motor cortex on day 3 but decreased in central nervous system tissues over time. These data demonstrate the requisite safety of intracerebral M032 administration for consideration as a therapeutic for treating malignant brain tumors.
C1 [Roth, Justin C.; Cassady, Kevin A.; Cody, James J.; Parker, Jackie N.; Price, Kathleen H.; Whitley, Richard J.; Markert, James M.] Univ Alabama Birmingham, Dept Pediat, Div Infect Dis, Birmingham, AL 35294 USA.
[Coleman, Jennifer M.; Gillespie, G. Yancey; Whitley, Richard J.; Markert, James M.] Univ Alabama Birmingham, Dept Neurosurg, Birmingham, AL 35294 USA.
[Carroll, Steven L.] Univ Alabama Birmingham, Dept Pathol, Div Neuropathol, Birmingham, AL 35294 USA.
[Gillespie, G. Yancey; Whitley, Richard J.; Markert, James M.] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA.
[Gillespie, G. Yancey] Univ Alabama Birmingham, Dept Cell Biol, Birmingham, AL 35294 USA.
[Whitley, Richard J.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA.
[Markert, James M.] Univ Alabama Birmingham, Dept Physiol & Biophys, Birmingham, AL 35294 USA.
[Peggins, James O.] NCI, Bethesda, MD 20892 USA.
[Noker, Patricia E.; Powers, Nicholas W.; Grimes, Sheila D.] So Res Inst, Birmingham, AL 35205 USA.
RP Markert, JM (reprint author), Univ Alabama Birmingham, Dept Neurosurg FOT 1050, 1530,3rd Ave South, Birmingham, AL 35294 USA.
EM markert@uab.edu
FU National Institutes of Health, National Cancer Institute [P01 CA71933,
P20 CA151129]; Department of Defense [W81XWH-11-1-0498]; RAID program of
the Developmental Therapeutics Program in the Division of Cancer
Treatment and Diagnosis of the National Cancer Institute
FX This work was supported by the National Institutes of Health, National
Cancer Institute Grants P01 CA71933 (J.M.M., J.C.R., K. A. C., G.Y.G.,
and R.J.W.) and P20 CA151129 (J.M.M., G.Y.G., K. A. C.), as well as
Department of Defense Grant W81XWH-11-1-0498 (J.M.M, G.Y.G., K. A. C.).
This research was also supported in part by the RAID program of the
Developmental Therapeutics Program in the Division of Cancer Treatment
and Diagnosis of the National Cancer Institute. (J.M.M.). We would also
like to posthumously acknowledge Dr. Ronna Fulton, from Fulton
Veterinary Clinical Pathology Consulting, for her clinical assessment of
the NHP study samples.
NR 61
TC 10
Z9 11
U1 2
U2 7
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 2324-8637
EI 2324-8645
J9 HUM GENE THER CL DEV
JI Hum. Gene Ther. Clin. Dev.
PD MAR 1
PY 2014
VL 25
IS 1
BP 16
EP 27
DI 10.1089/humc.2013.201
PG 12
WC Biotechnology & Applied Microbiology; Critical Care Medicine; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; General & Internal Medicine;
Research & Experimental Medicine
GA AS8BT
UT WOS:000344476100003
PM 24649838
ER
PT J
AU Xie, QQ
Ding, LP
Wei, Y
Ito, Y
AF Xie, Qianqian
Ding, Liping
Wei, Yun
Ito, Yoichiro
TI Determination of Major Components and Fingerprint Analysis of Flaveria
bidentis (L.) Kuntze
SO JOURNAL OF CHROMATOGRAPHIC SCIENCE
LA English
DT Article
ID SULFATED FLAVONOIDS; COMPOSITAE
AB A sensitive high-performance liquid chromatography method coupled with photodiode array detection was developed for the simultaneous determination of six major constituents in Flaveria bidentis (L.) Kuntze: hyperoside, patuletin-3-O-glucoside, isorhamnetin 3-sulfate, astragalin, 6-methoxykaempferol-3-O-galactoside and alpha-terthienyl. The chemical fingerprint of Flaveria bidentis (L.) Kuntze leaves was established using raw materials of 12 batches in China. The chromatographic separations were obtained by using an Eclipse XDB-C18 reserved-phase column (150 x 4.6 mm i.d., 5 mu m) using gradient elution with water (0.0125% trifluoroacetic acid, v/v) and acetonitrile at a flow rate of 1.0 mL/min, an operating temperature of 30 degrees C and a detection wavelength of 360 nm. The new method was validated by linearity, limits of detection and quantification, precision, reproducibility, stability and recovery, and was also successfully applied to the simultaneous determination of components in Flaveria bidentis (L.) Kuntze. The results indicate that this multi-component determination method in combination with chromatographic fingerprint analysis is suitable for the quantitative analysis and identification of Flaveria bidentis (L.) Kuntze.
C1 [Xie, Qianqian; Ding, Liping; Wei, Yun] Beijing Univ Chem Technol, State Key Lab Chem Resource Engn, Beijing 100029, Peoples R China.
[Ito, Yoichiro] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Wei, Y (reprint author), Beijing Univ Chem Technol, State Key Lab Chem Resource Engn, Beijing 100029, Peoples R China.
EM weiyun@mail.buct.edu.cn
FU Special Fund for Agro-scientific Research in the Public Interest
[200803022, 201103027]; Program for New Century Excellent Talents in
University [NCET-11-0563]; National Natural Science Foundation of China
[21075007]
FX Financial support by Special Fund for Agro-scientific Research in the
Public Interest (projects 200803022 and 201103027), Program for New
Century Excellent Talents in University (NCET-11-0563) and the National
Natural Science Foundation of China (Project 21075007) are gratefully
acknowledged.
NR 20
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Z9 2
U1 1
U2 6
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0021-9665
EI 1945-239X
J9 J CHROMATOGR SCI
JI J. Chromatogr. Sci.
PD MAR
PY 2014
VL 52
IS 3
BP 252
EP 257
DI 10.1093/chromsci/bmt020
PG 6
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA AQ4AG
UT WOS:000342734000010
PM 23515193
ER
PT J
AU Clements, N
Sarkar, SK
Zhao, ZG
Kim, DY
AF Clements, Nicolle
Sarkar, Sanat K.
Zhao, Zhigen
Kim, Dong-Yun
TI APPLYING MULTIPLE TESTING PROCEDURES TO DETECT CHANGE IN EAST AFRICAN
VEGETATION
SO ANNALS OF APPLIED STATISTICS
LA English
DT Article
DE False discovery rate; directional false discovery rate; NDVI; East
Africa vegetation
ID FALSE DISCOVERY RATE; TIME-SERIES; GROWTH; RATES
AB The study of vegetation fluctuations gives valuable information toward effective land use and development. We consider this problem for the East African region based on the Normalized Difference Vegetation Index (NDVI) series from satellite remote sensing data collected between 1982 and 2006 over 8-kilometer grid points. We detect areas with significant increasing or decreasing monotonic vegetation changes using a multiple testing procedure controlling the mixed directional false discovery rate (mdFDR). Specifically, we use a three-stage directional Benjamini-Hochberg (BH) procedure with proven mdFDR control under independence and a suitable adaptive version of it. The performance of these procedures is studied through simulations before applying them to the vegetation data. Our analysis shows increasing vegetation in the Northern hemisphere as well as coastal Tanzania and generally decreasing Southern hemisphere vegetation trends, which are consistent with historical evidence.
C1 [Clements, Nicolle] St Josephs Univ, Philadelphia, PA 19131 USA.
[Sarkar, Sanat K.; Zhao, Zhigen] Temple Univ, Philadelphia, PA 19122 USA.
[Kim, Dong-Yun] NIH, Off Biostat Res, Bethesda, MD 20892 USA.
RP Clements, N (reprint author), St Josephs Univ, Mandeville 349,5600 City Ave, Philadelphia, PA 19131 USA.
EM nclement@sju.edu; sanat@temple.edu; zhaozhg@temple.edu;
kimd10@nhlbi.nih.gov
FU NSF [DMS-10-06344, DMS-12-08735]; National Science Foundation
Biocomplexity of Coupled Human and Natural Systems Program [BCS/CNH
0709671]
FX The NDVI data set was collected as part of a Michigan State University
research project, namely, the "Dynamic Interactions among People,
Livestock, and Savanna Ecosystems under Climate Change" project (funded
by the National Science Foundation Biocomplexity of Coupled Human and
Natural Systems Program, Award No. BCS/CNH 0709671). We thank the
anonymous referees for their constructive comments which have helped to
improve the quality of the paper.
NR 24
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U1 1
U2 4
PU INST MATHEMATICAL STATISTICS
PI CLEVELAND
PA 3163 SOMERSET DR, CLEVELAND, OH 44122 USA
SN 1932-6157
J9 ANN APPL STAT
JI Ann. Appl. Stat.
PD MAR
PY 2014
VL 8
IS 1
BP 286
EP 308
DI 10.1214/13-AOAS686
PG 23
WC Statistics & Probability
SC Mathematics
GA AP9KT
UT WOS:000342399400012
ER
PT J
AU Park, Y
Wang, S
Kitahara, CM
Moore, SC
de Gonzalez, AB
Bernstein, L
Chang, ET
Flint, AJ
Freedman, DM
Gaziano, JM
Hoover, RN
Linet, MS
Purdue, M
Robien, K
Schairer, C
Sesso, HD
White, E
Willcox, BJ
Thun, MJ
Hartge, P
Willett, WC
AF Park, Yikyung
Wang, Sophia
Kitahara, Cari M.
Moore, Steven C.
de Gonzalez, Amy Berrington
Bernstein, Leslie
Chang, Ellen T.
Flint, Alan J.
Freedman, D. Michal
Gaziano, J. Michael
Hoover, Robert N.
Linet, Martha S.
Purdue, Mark
Robien, Kim
Schairer, Catherine
Sesso, Howard D.
White, Emily
Willcox, Bradley J.
Thun, Michael J.
Hartge, Patricia
Willett, Walter C.
TI Body Mass Index and Risk of Death in Asian Americans
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Article
ID CAUSE-SPECIFIC MORTALITY; PROSPECTIVE COHORT; UNITED-STATES; ALL-CAUSE;
OBESITY; WOMEN; WEIGHT; ASSOCIATION; OVERWEIGHT; ADULTS
AB Objectives. We investigated the association between body mass index (BMI) and mortality among Asian Americans.
Methods. We pooled data from prospective cohort studies with 20 672 Asian American adults with no baseline cancer or heart disease history. We estimated hazard ratios and 95% confidence intervals (CIs) with Cox proportional hazards models.
Results. A high, but not low, BMI was associated with increased risk of total mortality among individuals aged 35 to 69 years. The BMI was not related to total mortality among individuals aged 70 years and older. With a BMI 22.5 to < 25 as the reference category among never-smokers aged 35 to 69 years, the hazard ratios for total mortality were 0.83 (95% CI = 0.47, 1.47) for BMI 15 to < 18.5; 0.91 (95% CI = 0.62, 1.32) for BMI 18.5 to < 20; 1.08 (95% CI = 0.86, 1.36) for BMI 20 to < 22.5; 1.14 (95% CI = 0.90, 1.44) for BMI 25 to < 27.5; 1.13 (95% CI = 0.79, 1.62) for BMI 27.5 to < 30; 1.82 (95% CI = 1.25, 2.64) for BMI 30 to < 35; and 2.09 (95% CI = 1.06, 4.11) for BMI 35 to 50. Higher BMI was also related to increased cardiovascular disease and cancer mortality.
Conclusions. High BMI is associated with increased mortality risk among Asian Americans.
C1 [Park, Yikyung; Kitahara, Cari M.; Moore, Steven C.; de Gonzalez, Amy Berrington; Freedman, D. Michal; Hoover, Robert N.; Linet, Martha S.; Purdue, Mark; Schairer, Catherine; Hartge, Patricia] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Wang, Sophia; Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Div Canc Etiol, Dept Populat Sci, Duarte, CA 91010 USA.
[Wang, Sophia; Bernstein, Leslie] City Hope Natl Med Ctr, Duarte, CA USA.
[Chang, Ellen T.] Exponent Inc, Menlo Pk, CA USA.
[Flint, Alan J.; Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Gaziano, J. Michael; Sesso, Howard D.; Willett, Walter C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med, Boston, MA 02115 USA.
[Robien, Kim] George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Epidemiol & Biostat, Washington, DC USA.
[Robien, Kim] George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Exercise Sci, Washington, DC USA.
[White, Emily] Univ Washington, Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Dept Epidemiol, Seattle, WA 98195 USA.
[Willcox, Bradley J.] Pacific Hlth Res & Educ Inst, Honolulu, HI USA.
[Willcox, Bradley J.] Queens Med Ctr, Honolulu, HI USA.
[Thun, Michael J.] Amer Canc Soc, Dept Epidemiol Epidemiol & Surveillance Res, Atlanta, GA 30329 USA.
RP Park, Y (reprint author), NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
EM parkyik@mail.nih.gov
RI Moore, Steven/D-8760-2016; Kitahara, Cari/R-8267-2016;
OI Moore, Steven/0000-0002-8169-1661; Robien, Kim/0000-0002-2120-2280;
Park, Yikyung/0000-0002-6281-489X
FU National Institutes of Health [UM1CA167752, CA 097193, CA 34944, CA
40360, HL 26490, HL 34595]; National Cancer Institute at the National
Institutes of Health [R03 CA135687, R01 CA77398, K05 CA136967];
California Breast Cancer Research fund [97-10500]; California Breast
Cancer Act
FX This study was supported by the Intramural Research Program of the
National Institutes of Health. The California Teachers Study was
supported by the National Cancer Institute at the National Institutes of
Health (grants R03 CA135687, R01 CA77398, and K05 CA136967), the
California Breast Cancer Research fund (contract 97-10500), and the
California Breast Cancer Act of 1993. The Health Professionals Follow-up
Study is supported by the National Institutes of Health (grant
UM1CA167752). The Physicians' Health Study was supported by the National
Institutes of Health (grants CA 097193, CA 34944, CA 40360, HL 26490,
and HL 34595).
NR 35
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U1 0
U2 3
PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
EI 1541-0048
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD MAR
PY 2014
VL 104
IS 3
BP 520
EP 525
DI 10.2105/AJPH.2013.301573
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AP0LP
UT WOS:000341753300046
PM 24432919
ER
PT J
AU Mallon, BS
Hamilton, RS
Kozhich, OA
Johnson, KR
Fann, YC
Rao, MS
Robey, PG
AF Mallon, Barbara S.
Hamilton, Rebecca S.
Kozhich, Olga A.
Johnson, Kory R.
Fann, Yang C.
Rao, Mahendra S.
Robey, Pamela G.
TI Comparison of the molecular profiles of human embryonic and induced
pluripotent stem cells of isogenic origin
SO STEM CELL RESEARCH
LA English
DT Article
ID GENE-EXPRESSION SIGNATURES; ALLELIC VARIATION; COPY NUMBER; HUMAN ES;
METHYLATION; PATIENT; MEMORY
AB Many studies have compared the genetic and epigenetic profiles of human induced pluripotent stem cells (hiPSCs) to human embryonic stem cells (hESCs) and yet the picture remains unclear. To address this, we derived a population of neural precursor cells (NPCs) from the H1 (WA01) hESC line and generated isogenic iPSC lines by reprogramming. The gene expression and methylation profile of three lines were compared to the parental line and intermediate NPC population. We found no gene probe with expression that differed significantly between hESC and iPSC samples under undifferentiated or differentiated conditions. Analysis of the global methylation pattern also showed no significant difference between the two PSC populations. Both undifferentiated populations were distinctly different from the intermediate NPC population in both gene expression and methylation profiles. One point to note is that H1 is a male line and so extrapolation to female lines should be cautioned. However, these data confirm our previous findings that there are no significant differences between hESCs and hiPSCs at the gene expression or methylation level. (C) 2013 The Authors. Published by Elsevier B. V. All rights reserved.
C1 [Mallon, Barbara S.; Hamilton, Rebecca S.; Robey, Pamela G.] NINDS, NIH, Stem Cell Unit, Bethesda, MD 20892 USA.
[Kozhich, Olga A.] NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Johnson, Kory R.; Fann, Yang C.] NINDS, Bioinformat Sect, Intramural IT & Bioinformat Program, NIH, Bethesda, MD 20892 USA.
[Rao, Mahendra S.] NIH, Ctr Regenerat Med, Bethesda, MD 20892 USA.
[Robey, Pamela G.] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Mallon, BS (reprint author), NINDS, NIH, Stem Cell Unit, Bethesda, MD 20892 USA.
EM mallonb@mail.nih.gov
RI Robey, Pamela/H-1429-2011
OI Robey, Pamela/0000-0002-5316-5576
FU Intramural Research Program of the NIH, NINDS
FX This research was supported by the Intramural Research Program of the
NIH, NINDS.
NR 28
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Z9 19
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1873-5061
EI 1876-7753
J9 STEM CELL RES
JI Stem Cell Res.
PD MAR
PY 2014
VL 12
IS 2
BP 376
EP 386
DI 10.1016/j.scr.2013.11.010
PG 11
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology
SC Cell Biology; Biotechnology & Applied Microbiology
GA AP7VU
UT WOS:000342286600005
PM 24374290
ER
PT J
AU Kerever, A
Mercier, F
Nonaka, R
de Vega, S
Oda, Y
Zalc, B
Okada, Y
Hattori, N
Yamada, Y
Arikawa-Hirasawa, E
AF Kerever, Aurelien
Mercier, Frederic
Nonaka, Risa
de Vega, Susana
Oda, Yuka
Zalc, Bernard
Okada, Yohei
Hattori, Nobutaka
Yamada, Yoshihiko
Arikawa-Hirasawa, Eri
TI Perlecan is required for FGF-2 signaling in the neural stem cell niche
SO STEM CELL RESEARCH
LA English
DT Article
ID FIBROBLAST-GROWTH-FACTOR; ADULT SUBVENTRICULAR ZONE; MAMMALIAN BRAIN;
OLFACTORY-BULB; VASCULAR NICHE; CYCLIN D2; PROLIFERATION; NEUROGENESIS;
BINDING; PROTEOGLYCAN
AB In the adult subventricular zone (neurogenic niche), neural stem cells double-positive for two markers of subsets of neural stem cells in the adult central nervous system, glial fibrillary acidic protein and CD133, lie in proximity to fractones and to blood vessel basement membranes, which contain the heparan sulfate proteoglycan perlecan. Here, we demonstrate that perlecan deficiency reduces the number of both GFAP/CD133-positive neural stem cells in the subventricular zone and new neurons integrating into the olfactory bulb. We also show that FGF-2 treatment induces the expression of cyclin D2 through the activation of the Akt and Erk1/2 pathways and promotes neurosphere formation in vitro. However, in the absence of perlecan, FGF-2 fails to promote neurosphere formation. These results suggest that perlecan is a component of the neurogenic niche that regulates FGF-2 signaling and acts by promoting neural stem cell self-renewal and neurogenesis. (C) 2013 The Authors. Published by Elsevier B. V. All rights reserved.
C1 [Kerever, Aurelien; Nonaka, Risa; de Vega, Susana; Oda, Yuka; Arikawa-Hirasawa, Eri] Juntendo Univ, Grad Sch Med, Res Inst Dis Old Age, Tokyo 1138421, Japan.
[Mercier, Frederic] Univ Hawaii, John A Burns Sch Med, Dept Trop Med & Infect Dis, Honolulu, HI 96822 USA.
[Zalc, Bernard] Univ Paris 06, Ctr Rech, Inst Cerveau & Moelle Epiniere CRICM, UMRS 975, F-75013 Paris, France.
[Zalc, Bernard] Univ Paris 06, INSERM, U975, F-75013 Paris, France.
[Zalc, Bernard] CNRS, UMR 7225, F-75013 Paris, France.
[Okada, Yohei] Keio Univ, Sch Med, Dept Physiol, Shinjuku Ku, Tokyo 160, Japan.
[Okada, Yohei] Keio Univ, Sch Med, Kanrinmaru Project, Tokyo, Japan.
[Hattori, Nobutaka; Arikawa-Hirasawa, Eri] Juntendo Univ, Sch Med, Dept Neurol, Tokyo 113, Japan.
[Yamada, Yoshihiko] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA.
RP Arikawa-Hirasawa, E (reprint author), Juntendo Univ, Grad Sch Med, Res Inst Dis Old Age, Bunkyo Ku, Bldg 10,Room 606,2-1-1 Hongo, Tokyo 1138421, Japan.
EM ehirasaw@juntendo.ac.jp
FU MEXT; Ministry of Education, Culture, Sports Science, and Technology of
Japan [17082008, 2230023]; Intramural Program of the NIDCR, National
Institutes of Health; program "Investissements d'avenir"
[ANR-10-IAIHU-06]
FX This work was supported by grants from MEXT-Supported Program for the
Strategic Research Foundation at Private Universities (2011-2015) and
the Ministry of Education, Culture, Sports Science, and Technology of
Japan (17082008 and 2230023 to E. A-H.) and the Intramural Program of
the NIDCR, National Institutes of Health (Y.Y.). Bernard Zalc has
received funding from the program "Investissements d'avenir"
ANR-10-IAIHU-06.
NR 53
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U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1873-5061
EI 1876-7753
J9 STEM CELL RES
JI Stem Cell Res.
PD MAR
PY 2014
VL 12
IS 2
BP 492
EP 505
DI 10.1016/j.scr.2013.12.009
PG 14
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology
SC Cell Biology; Biotechnology & Applied Microbiology
GA AP7VU
UT WOS:000342286600014
PM 24434631
ER
PT J
AU Lea, CS
Efird, JT
Toland, AE
Lewis, DR
Phillips, CJ
AF Lea, C. Suzanne
Efird, Jimmy T.
Toland, Amanda E.
Lewis, Denise R.
Phillips, Christopher J.
TI Melanoma Incidence Rates in Active Duty Military Personnel Compared With
a Population-Based Registry in the United States, 2000-2007
SO MILITARY MEDICINE
LA English
DT Article
ID CANCER INCIDENCE; SUN EXPOSURE; MALIGNANT-MELANOMA; CUTANEOUS MELANOMA;
SKIN CANCERS; AIR-FORCE; RISK; METAANALYSIS; WOMEN
AB Objectives: This study was conducted to investigate whether incidence rates of malignant cutaneous melanoma in U.S. Department of Defense active duty military personnel differed from rates in the U.S. general population between 2000 and 2007. Methods: The study population included active duty military personnel and the general population aged 18 to 56 years. Data were obtained from the U.S. Department of Defense medical data systems and from the Surveillance Epidemiology and End Results program. Melanoma risk was estimated by incidence rate ratios (IRRs). Results: Melanoma risk was higher among active duty personnel than the general population (IRR = 1.62, 95% confidence interval = 1.40-1.86). Incidence rates were higher for white military personnel than for white rates in general population (36.89 and 23.05 per 100,000 person-years, respectively). Rates were also increased for military men and women compared with SEER (men, 25.32 and 16.53 per 100,000; women, 30.00 and 17.55 per 100,000). Air Force service personnel had the highest rates and Army had the lowest. Conclusion: Melanoma rates were marginally higher among active duty military personnel than the general population between 2000 and 2007.
C1 [Lea, C. Suzanne; Efird, Jimmy T.] E Carolina Univ, Brody Sch Med, Dept Publ Hlth, Greenville, NC 27834 USA.
[Toland, Amanda E.] Ohio State Univ, Ctr Comprehens Canc, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA.
[Lewis, Denise R.] NCI, Surveillance Res Program, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA.
[Phillips, Christopher J.] Naval Hlth Res Ctr, Deployment Hlth Res Dept, San Diego, CA 92152 USA.
RP Lea, CS (reprint author), E Carolina Univ, Brody Sch Med, Dept Publ Hlth, Greenville, NC 27834 USA.
FU Deployment Health Research Department [60002]
FX We thank Zhuoqiao Wang, MS, with IMS, Inc., an NCI contractor, for
reviewing programming code and appreciate helpful comments from Dr.
Nancy Crum-Cianflone, Chair, Deployment Health Research Department,
Naval Health Research Center. This work represents report 12-60,
supported by the Deployment Health Research Department, under work unit
number 60002.
NR 31
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U1 4
U2 5
PU ASSOC MILITARY SURG US
PI BETHESDA
PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA
SN 0026-4075
EI 1930-613X
J9 MIL MED
JI Milit. Med.
PD MAR
PY 2014
VL 179
IS 3
BP 247
EP 253
DI 10.7205/MILMED-D-13-00356
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA AN7UJ
UT WOS:000340806200007
PM 24594457
ER
PT J
AU Neta, G
Hatch, M
Kitahara, CM
Ostroumova, E
Bolshova, EV
Tereschenko, VP
Tronko, MD
Brenner, AV
AF Neta, Gila
Hatch, Maureen
Kitahara, Cari M.
Ostroumova, Evgenia
Bolshova, Elena V.
Tereschenko, Valery P.
Tronko, Mykola D.
Brenner, Alina V.
TI In Utero Exposure to Iodine-131 from Chernobyl Fallout and
Anthropometric Characteristics in Adolescence
SO RADIATION RESEARCH
LA English
DT Article
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CHILDHOOD-CANCER SURVIVOR; ATOMIC-BOMB
SURVIVORS; BODY-MASS-INDEX; THYROID-CANCER; ADULT SURVIVORS; RADIATION;
RADIOIODINE; HIROSHIMA; NAGASAKI
AB Prenatal exposure to external radiation has been linked to growth retardation among atomic bomb survivors in adolescence. It is unclear from previous studies whether in utero exposure to internal radiation such as iodine-131 (I-131), which concentrates in the thyroid gland, has an effect on physical growth. We examined the associations between estimated thyroid gland dose from prenatal exposure to I-131 and self-reported height and weight in a cohort of 2,460 individuals exposed to radioactive fallout from the 1986 Chernobyl nuclear accident [mean I-131 dose 72 (mGy)] and screened for thyroid diseases in adolescence. Using multivariable linear regression models, we estimated the mean differences in height, weight and body mass index (BMI) per unit increase in dose (100 mGy) in models adjusted for gender, age at examination, type of residence (rural/urban) and presence of thyroid disease diagnosed at screening. All of the adjustment factors as well as the trimester of exposure were evaluated as potential modifiers of the dose response. Overall, no significant dose response was found for height (P = 0.29), weight (P = 0.14) or BMI (P = 0.16). We found significant modification of the dose response for weight and BMI by presence/absence of thyroid disease (P = 0.02 and P = 0.03, respectively), but not for other factors. In individuals without thyroid disease (n = 1,856), there was a weak, significant association between I-131 thyroid dose and higher weight (210 g per 100 mGy, P = 0.02) or BMI (70 g/m(2) per 100 mGy, P 0.02) that depended on individuals (n 52) exposed to >= 500 mGy. In individuals with thyroid disease (n = 579, 67.4% with simple diffuse goiter) no significant association with I-131 for weight (P = 0.14) or BMI (P = 0.14) was found. These results do not support the hypothesis that in utero exposure to I-131 at levels experienced by a majority of study subjects may be associated with meaningful differences in adolescent anthropometry. However, additional studies are needed to clarify whether in utero exposure to I-131 at levels > = 500 mGy may be associated with increases in weight/BMI and to evaluate the confounding or modifying role of thyroid disease, past iodine deficiency, maternal and prenatal/postnatal factors. (C) 2014 by Radiation Research Society
C1 [Neta, Gila; Hatch, Maureen; Kitahara, Cari M.; Ostroumova, Evgenia; Brenner, Alina V.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20852 USA.
[Bolshova, Elena V.; Tereschenko, Valery P.; Tronko, Mykola D.] Inst Endocrinol & Metab, Kiev, Ukraine.
RP Neta, G (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv,EPS, Room 7092,6120 Execut Blvd, Bethesda, MD 20852 USA.
EM netagil@mail.nih.gov
RI Kitahara, Cari/R-8267-2016
FU Intramural Research Program of the Division of Cancer Epidemiology and
Genetics, National Cancer Institute at the National Institutes of Health
FX We would like to acknowledge the contributions to this study of Drs.
Galina A. Zamotaeva, Ihor P. Paster, Ludmila V. Chaykovskaya, Victor I.
Kravchenko, Oleksandr V. Zvinchuk and Victor M. Shpak, all of the
Institute of Endocrinology and Metabolism in Kiev, Ukraine. This
research was supported, in part by the Intramural Research Program of
the Division of Cancer Epidemiology and Genetics, National Cancer
Institute at the National Institutes of Health.
NR 38
TC 1
Z9 1
U1 1
U2 7
PU RADIATION RESEARCH SOC
PI LAWRENCE
PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA
SN 0033-7587
EI 1938-5404
J9 RADIAT RES
JI Radiat. Res.
PD MAR
PY 2014
VL 181
IS 3
BP 293
EP 301
DI 10.1667/RR13304.1
PG 9
WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology,
Nuclear Medicine & Medical Imaging
GA AO4KR
UT WOS:000341307200007
PM 24611659
ER
PT J
AU Zhao, XN
Usdin, K
AF Zhao, Xiao-Nan
Usdin, Karen
TI Gender and Cell-Type-Specific Effects of the Transcription-Coupled
Repair Protein, ERCC6/CSB, on Repeat Expansion in a Mouse Model of the
Fragile X-Related Disorders
SO HUMAN MUTATION
LA English
DT Article
DE CSB; ERCC6; repeat expansion; Fragile X-related; ataxia; primary ovarian
insufficiency; transcription-coupled repair
ID NUCLEOTIDE EXCISION-REPAIR; ESTROGEN-RECEPTOR-ALPHA; RNA-POLYMERASE-II;
CAG REPEAT; CGG-REPEAT; DNA-REPAIR; TRANSGENIC MICE; TREMOR/ATAXIA
SYNDROME; GENETIC INSTABILITY; PREMUTATION MICE
AB The repeat expansion diseases are human genetic disorders that arise from the expansion of a tandem-repeat tract. The Fragile X-related disorders are members of this disease group in which the repeat unit is CGG/CCG and is located in the 5 ' untranslated region of the FMR1 gene. Affected individuals often show mosaicism with respect to repeat number resulting from both expansion and contraction of the repeat tract; however, the mechanism responsible for these changes in repeat number is unknown. The work from a variety of model systems suggests that transcription-coupled repair (TCR) may contribute to repeat instability in diseases resulting from CAG/CTG-repeat expansion. To test whether TCR could contribute to repeat instability in the Fragile X-related disorders, we tested the effect of mutations in Csb (Cockayne syndrome group B), a gene essential for TCR, in a knock-in mouse model of these disorders. We found that the loss of CSB affects expansions in a gender and cell-type-specific manner. Our data also show an unanticipated gender difference in instability even in Csb(+/+) animals that may have implications for our understanding of the mechanism of repeat expansion in the FX mouse model and perhaps for humans as well. Hum Mutat 35:341-349, 2014. Published 2013 Wiley Periodicals, Inc.
C1 [Zhao, Xiao-Nan; Usdin, Karen] NIDDK, Sect Gene Struct & Dis, Lab Cell & Mol Biol, NIH, Bethesda, MD 20892 USA.
RP Usdin, K (reprint author), NIH, Bldg 8,Room 2A19,8 Ctr DR MSC 0830, Bethesda, MD 20892 USA.
EM ku@helix.nih.gov
RI Zhao, Xiaonan/S-3139-2016
FU Intramural Program of the NIDDK, National Institutes of Health
[DK057808-05]
FX Contract grant sponsor: Intramural Program of the NIDDK, National
Institutes of Health (DK057808-05).
NR 58
TC 10
Z9 10
U1 1
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1059-7794
EI 1098-1004
J9 HUM MUTAT
JI Hum. Mutat.
PD MAR
PY 2014
VL 35
IS 3
BP 341
EP 349
DI 10.1002/humu.22495
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA AB6OP
UT WOS:000331909600011
PM 24352881
ER
PT J
AU Kleinman, S
Busch, MP
Murphy, EL
Shan, H
Ness, P
Glynn, SA
AF Kleinman, Steven
Busch, Michael P.
Murphy, Edward L.
Shan, Hua
Ness, Paul
Glynn, Simone A.
CA Natl Heart Lung Blood Inst Recipie
TI The National Heart, Lung, and Blood Institute Recipient Epidemiology and
Donor Evaluation Study (REDS-III): a research program striving to
improve blood donor and transfusion recipient outcomes
SO TRANSFUSION
LA English
DT Article
ID SICKLE-CELL-DISEASE; IMMUNODEFICIENCY-VIRUS-INFECTION; RISK-FACTORS;
IRON-DEFICIENCY; UNITED-STATES; BRAZIL; TRANSMISSION; MORTALITY; DENGUE;
ALLOIMMUNIZATION
AB BACKGROUND: The Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) is a 7-year multi-center transfusion safety research initiative launched in 2011 by the National Heart, Lung, and Blood Institute.
STUDY DESIGN AND METHODS: The domestic component involves four blood centers, 12 hospitals, a data coordinating center, and a central laboratory. The international component consists of distinct programs in Brazil, China, and South Africa, which involve US and in-country investigators.
RESULTS: REDS-III is using two major methods to address key research priorities in blood banking and transfusion medicine. First, there will be numerous analyses of large "core" databases; the international programs have each constructed a donor and donation database while the domestic program has established a detailed research database that links data from blood donors and their donations, the components made from these donations, and data extracts from the electronic medical records of the recipients of these components. Second, there are more than 25 focused research protocols involving transfusion recipients, blood donors, or both that either are in progress or are scheduled to begin within the next 3 years. Areas of study include transfusion epidemiology and blood utilization, transfusion outcomes, noninfectious transfusion risks, human immunodeficiency virus-related safety issues (particularly in the international programs), emerging infectious agents, blood component quality, donor health and safety, and other donor issues.
CONCLUSIONS: It is intended that REDS-III serve as an impetus for more widespread recipient and linked donor-recipient research in the United States as well as to help assure a safe and available blood supply in the United States and in international locations.
C1 [Kleinman, Steven] Univ British Columbia, Dept Pathol, Victoria, BC, Canada.
[Busch, Michael P.; Murphy, Edward L.] Blood Syst Res Inst, San Francisco, CA USA.
[Busch, Michael P.] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA.
[Murphy, Edward L.] Univ Calif San Francisco, Dept Lab Med & Epidemiol Biostat, San Francisco, CA 94143 USA.
[Shan, Hua] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA.
[Ness, Paul] Johns Hopkins Univ, Dept Pathol & Med, Baltimore, MD USA.
[Ness, Paul] Johns Hopkins Med Inst, Dept Transfus Med, Baltimore, MD 21205 USA.
[Glynn, Simone A.] NHLBI, Dept Transfus Med, NIH, Bethesda, MD 20892 USA.
[Glynn, Simone A.] NHLBI, Cellular Therapeut Branch, NIH, Bethesda, MD 20892 USA.
RP Kleinman, S (reprint author), 1281 Rockcrest Ave, Victoria, BC V9A 4W4, Canada.
EM skleinman@shaw.ca
FU NHLBI [NHLBI HHSN2682011-00001I, NHLBI HHSN2682011-00002I, NHLBI
HHSN2682011-00003I, NHLBI HHSN2682011-00004I, NHLBI HHSN2682011-00005I,
NHLBI HHSN2682011-00006I, NHLBI HHSN2682011-00007I, NHLBI
HHSN2682011-00008I, NHLBI HHSN2682011-00009I]
FX REDS-III is supported by NHLBI contracts NHLBI HHSN2682011-00001I,
-00002I, -00003I, -00004I, -00005I, -00006I, -00007I, -00008I, and
-00009I.
NR 70
TC 23
Z9 23
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
EI 1537-2995
J9 TRANSFUSION
JI Transfusion
PD MAR
PY 2014
VL 54
IS 3
SI SI
BP 942
EP 955
DI 10.1111/trf.12468
PN 2
PG 14
WC Hematology
SC Hematology
GA AM9GI
UT WOS:000340188500027
PM 24188564
ER
PT J
AU Ochi, F
Fujiwara, H
Tanimoto, K
Asai, H
Miyazaki, Y
Okamoto, S
Mineno, J
Kuzushima, K
Shiku, H
Barrett, J
Ishii, E
Yasukawa, M
AF Ochi, Fumihiro
Fujiwara, Hiroshi
Tanimoto, Kazushi
Asai, Hiroaki
Miyazaki, Yukihiro
Okamoto, Sachiko
Mineno, Junichi
Kuzushima, Kiyotaka
Shiku, Hiroshi
Barrett, John
Ishii, Eiichi
Yasukawa, Masaki
TI Gene-Modified Human alpha/beta-T Cells Expressing a Chimeric CD16-CD3
zeta Receptor as Adoptively Transferable Effector Cells for Anticancer
Monoclonal Antibody Therapy
SO CANCER IMMUNOLOGY RESEARCH
LA English
DT Article
ID FC-GAMMA-RIIIA; DEPENDENT CELLULAR CYTOTOXICITY; ANTILEUKEMIA
REACTIVITY; CANCER-IMMUNOTHERAPY; BREAST-CANCER; LEUKEMIA; LYMPHOMA;
POLYMORPHISM; LYMPHOCYTES; RITUXIMAB
AB The central tumoricidal activity of anticancer monoclonal antibodies (mAb) is exerted by Fc gamma R IIIa (CD16)-expressing effector cells in vivo via antibody-dependent cell-mediated cytotoxicity (ADCC), as observed for natural killer (NK) cells. In practice, chemotherapy-induced leukopenia and exhaustion of NK cells resulting from ADCC often hamper the clinical efficacy of cancer treatment. To circumvent this drawback, we examined in vivo the feasibility of T cells, gene-modified to express a newly generated affinity-matured (158V/V) chimeric CD16-CD3 zeta receptor (cCD16 zeta-T cells), as a transferable alternative effector for cancer mAb therapy. cCD16 zeta-T cells were readily expandable in ex vivo culture using anti-CD2/CD3/CD28 beads and recombinant human interleukin-2 (rhIL-2), and they successfully displayed ADCC-mediated tumoricidal activity in vitro. During ADCC, ligation of opsonized cancer cells to the introduced cCD16 zeta-T cells stimulated the effector cells to produce proinflammatory cytokines and release toxic granules through the activation of the Nuclear factor of activated T cells (NFAT) pathway after phosphorylation of the CD3 zeta chain. In parallel, these stimulated cCD16 zeta-T cells transiently proliferated and differentiated into effector memory T cells. In contrast, NK cells activated by rhIL-2 displayed similar ADCC activity, but failed to proliferate. Human cCD16 zeta-T cells infused concomitantly with anti-CD20 mAb synergistically inhibited the growth of disseminated Raji cells, a CD20(+) lymphoma cell line, in immunodeficient mice, whereas similarly infused rhIL-2-treated NK cells survived for a shorter time and displayed less effective tumor suppression. Our findings strongly suggest the clinical feasibility of cCD16 zeta-T cells as adoptively transferable ADCC effector cells that could potentially enhance the clinical responses mediated by currently available anticancer mAbs. (C) 2014 AACR.
C1 [Ochi, Fumihiro; Fujiwara, Hiroshi; Tanimoto, Kazushi; Asai, Hiroaki; Miyazaki, Yukihiro; Yasukawa, Masaki] Ehime Univ, Dept Hematol Clin Immunol & Infect Dis, Grad Sch Med, Toon, Ehime 7910295, Japan.
[Ochi, Fumihiro; Ishii, Eiichi] Ehime Univ, Dept Pediat, Grad Sch Med, Toon, Ehime 7910295, Japan.
[Okamoto, Sachiko; Mineno, Junichi] Takara Bio Inc, Ctr Cell & Gene Therapy, Shiga, Japan.
[Kuzushima, Kiyotaka] Aichi Canc Ctr, Div Immunol, Aichi, Japan.
[Shiku, Hiroshi] Mie Univ, Grad Sch Med, Dept Canc Vaccine & Immuno Gene Therapy, Tsu, Mie, Japan.
[Tanimoto, Kazushi; Barrett, John] NHLBI, Hematol Branch, NIH, Bethesda, MD USA.
RP Fujiwara, H (reprint author), Ehime Univ, Dept Hematol Clin Immunol & Infect Dis, Grad Sch Med, Toon, Ehime 7910295, Japan.
EM yunarief@m.ehime-u.ac.jp; yasukawa@m.ehime-u.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology of Japan;
Ministry of Health, Labor and Welfare
FX This work was supported in part by grants from the Ministry of
Education, Culture, Sports, Science and Technology of Japan to H.
Fujiwara and M. Yasukawa, and a Grant-in-Aid for Cancer Research from
the Ministry of Health, Labor and Welfare to M. Yasukawa.
NR 41
TC 2
Z9 2
U1 3
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 2326-6066
EI 2326-6074
J9 CANCER IMMUNOL RES
JI Cancer Immunol. Res.
PD MAR
PY 2014
VL 2
IS 3
BP 249
EP 262
DI 10.1158/2326-6066.CIR-13-0099-T
PG 14
WC Oncology; Immunology
SC Oncology; Immunology
GA AM7GH
UT WOS:000340032800008
PM 24778321
ER
PT J
AU Shankar, A
Kumar, S
Iskander, A
Varma, NRS
Janic, B
deCarvalho, A
Mikkelsen, T
Frank, JA
Ali, MM
Knight, RA
Brown, S
Arbab, AS
AF Shankar, Adarsh
Kumar, Sanath
Iskander, Asm
Varma, Nadimpalli R. S.
Janic, Branislava
deCarvalho, Ana
Mikkelsen, Tom
Frank, Joseph A.
Ali, Meser M.
Knight, Robert A.
Brown, Stephen
Arbab, Ali S.
TI Subcurative radiation significantly increases cell proliferation,
invasion, and migration of primary glioblastoma multiforme in vivo
SO CHINESE JOURNAL OF CANCER
LA English
DT Article
DE Glioblastoma multiforme; radiation; treatment resistance; invasion
ID ENDOTHELIAL GROWTH-FACTOR; PANCREATIC-CANCER CELLS; MALIGNANT GLIOMAS;
ANTIANGIOGENIC THERAPIES; IONIZING-RADIATION; TUMOR ANGIOGENESIS;
SIGNALING PATHWAY; BRAIN; RADIOTHERAPY; IRRADIATION
AB Tumor cell proliferation, infiltration, migration, and neovascularization are known causes of treatment resistance in glioblastoma multiforme (GBM). The purpose of this study was to determine the effect of radiation on the growth characteristics of primary human GBM developed in a nude rat. Primary GBM cells grown from explanted GBM tissues were implanted orthotopically in nude rats. Tumor growth was confirmed by magnetic resonance imaging on day 77 (baseline) after implantation. The rats underwent irradiation to a dose of 50 Gy delivered subcuratively on day 84 postimplantation (n = 8), or underwent no radiation (n = 8). Brain tissues were obtained on day 112 (nonirradiated) or day 133 (irradiated). Immunohistochemistry was performed to determine tumor cell proliferation (Ki-67) and to assess the expression of infiltration marker (matrix metalloproteinase-2, MMP-2) and cell migration marker (CD44). Tumor neovascularization was assessed by microvessel density using von-Willebrand factor (vWF) staining. Magnetic resonance imaging showed well-developed, infiltrative tumors in 11 weeks postimplantation. The proportion of Ki-67-positive cells in tumors undergoing radiation was (71 +/- 15)% compared with (25 +/- 12)% in the nonirradiated group (P = 0.02). The number of MMP-2-positive areas and proportion of CD44-positive cells were also high in tumors receiving radiation, indicating great invasion and infiltration. Microvessel density analysis did not show a significant difference between nonirradiated and irradiated tumors. Taken together, we found that subcurative radiation significantly increased proliferation, invasion, and migration of primary GBM. Our study provides insights into possible mechanisms of treatment resistance following radiation therapy for GBM.
C1 [Shankar, Adarsh; Iskander, Asm; Varma, Nadimpalli R. S.; Janic, Branislava; Ali, Meser M.; Arbab, Ali S.] Henry Ford Hosp, Dept Radiol, Detroit, MI 48202 USA.
[Kumar, Sanath; Brown, Stephen] Henry Ford Hosp, Dept Radiat Oncol, Detroit, MI 48202 USA.
[deCarvalho, Ana; Mikkelsen, Tom] Henry Ford Hosp, Dept Neurosurg, Detroit, MI 48202 USA.
[Frank, Joseph A.; Knight, Robert A.] NIH, Lab Diagnost Radiol Res, Bethesda, MD 20892 USA.
Henry Ford Hosp, Dept Neurol, Detroit, MI 48202 USA.
[Brown, Stephen] Wayne State Univ, Dept Radiat Oncol, Sch Med, Detroit, MI 48202 USA.
[Arbab, Ali S.] Wayne State Univ, Dept Radiol, Sch Med, Detroit, MI 48202 USA.
RP Kumar, S (reprint author), Henry Ford Hosp, Dept Radiat Oncol, Detroit, MI 48202 USA.
EM skumar4@hfhs.org
OI deCarvalho, Ana C/0000-0003-1183-4548
FU National Institutes of Health (NIH) [K25CA129173, R01CA122031,
1R01CA160216]
FX We thank Thaiz Borin for her assistance during immunohistochemistry
analysis. This work was supported by grants from the National Institutes
of Health (NIH) [No. K25CA129173 (MMA), R01CA122031 (ASA), and
1R01CA160216 (ASA)].
NR 48
TC 4
Z9 4
U1 0
U2 5
PU SUN YAT SEN UNIV MED SCI WHO
PI GUANGZHOU
PA 651 DONGFENG RD E, GUANGZHOU, GUANGDONG 510060, PEOPLES R CHINA
SN 1000-467X
EI 1944-446X
J9 CHIN J CANCER
JI Chin. J. Cancer
PD MAR
PY 2014
VL 33
IS 3
BP 148
EP 158
DI 10.5732/cjc.013.10095
PG 11
WC Oncology
SC Oncology
GA AM2BB
UT WOS:000339652000004
PM 24016393
ER
PT J
AU Damiano, DL
AF Damiano, Diane L.
TI Progressive resistance exercise increases strength but does not improve
objective measures of mobility in young people with cerebral palsy
SO JOURNAL OF PHYSIOTHERAPY
LA English
DT Editorial Material
ID CHILDREN; ADOLESCENTS
C1 NIH, Ctr Clin, Bethesda, MD 20892 USA.
RP Damiano, DL (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA.
FU Intramural NIH HHS [Z99 CL999999]
NR 7
TC 6
Z9 6
U1 0
U2 9
PU AUSTRALIAN PHYSIOTHERAPY ASSOC
PI ST KILDA
PA LEVEL 3, 201 FITZROY ST, ST KILDA, 3182, AUSTRALIA
SN 1836-9553
EI 1836-9561
J9 J PHYSIOTHER
JI J. Physiother.
PD MAR
PY 2014
VL 60
IS 1
BP 58
EP 58
DI 10.1016/j.jphys.2013.12.010
PG 1
WC Orthopedics; Rehabilitation
SC Orthopedics; Rehabilitation
GA AL9GV
UT WOS:000339449500011
PM 24856945
ER
PT J
AU Gorelic, LS
AF Gorelic, Lester S.
TI DEPICTING the CREATION of a NATION The story Behind the murals About our
Founding Documents
SO PROLOGUE-QUARTERLY OF THE NATIONAL ARCHIVES AND RECORDS ADMINISTRATION
LA English
DT Article
C1 [Gorelic, Lester S.] NCI, Rockville, MD 20850 USA.
RP Gorelic, LS (reprint author), Natl Arch Bldg, Washington, DC 20408 USA.
NR 10
TC 0
Z9 0
U1 0
U2 0
PU NATL ARCHIVES RECORDS ADMINISTRATION
PI WASHINGTON
PA TRUST FUND BOARD, WASHINGTON, DC 20408 USA
SN 0033-1031
J9 PROLOGUE
JI Prologue
PD SPR
PY 2014
VL 46
IS 1
BP 44
EP 54
PG 11
WC History
SC History
GA AK4SV
UT WOS:000338415300007
ER
PT J
AU Tan, Y
Lam, TTY
Wu, CW
Lee, SS
Viboud, C
Zhang, RL
Weinberger, DM
AF Tan, Yi
Lam, Tommy Tsan-Yuk
Wu, Chunli
Lee, Shui-shan
Viboud, Cecile
Zhang, Renli
Weinberger, Daniel M.
TI Increasing similarity in the dynamics of influenza in two adjacent
subtropical Chinese cities following the relaxation of border
restrictions
SO JOURNAL OF GENERAL VIROLOGY
LA English
DT Article
ID EPIDEMIOLOGIC DYNAMICS; SPATIAL HIERARCHIES; HONG-KONG; SEASONALITY;
VIRUS; SYNCHRONY; EPIDEMICS; PATTERNS; WAVES
AB The drivers of influenza seasonality remain heavily debated, especially in tropical/subtropical regions where influenza activity can peak in winter, during the rainy season, or remain constant throughout the year. We compared the epidemiological and evolutionary patterns of seasonal influenza epidemics in Hong Kong and Shenzhen, two adjacent cities in subtropical southern China. This comparison represents a unique natural experiment, as connectivity between these two cities has increased over the past decade. We found that, whilst summer influenza epidemics in Shenzhen used to peak 1-3 months later than those in Hong Kong, the difference decreased after 2005 (P<0.0001). Phylogenetic analysis revealed that influenza isolates from Shenzhen have become genetically closer to those circulating in Hong Kong over time (P=0.045). Furthermore, although Shenzhen isolates used to be more distant from the global putative source of influenza viruses than isolates from Hong Kong (P<0.001), this difference has narrowed (P=0.02). Overall, our study reveals that influenza activities show remarkably distinct epidemiological and evolutionary patterns in adjacent subtropical cities and suggests that human mobility patterns can play a major role in influenza dynamics in the subtropics.
C1 [Tan, Yi; Viboud, Cecile; Weinberger, Daniel M.] NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Tan, Yi; Lee, Shui-shan] Chinese Univ Hong Kong, Stanley Ho Ctr Emerging Infect Dis, Sch Publ Hlth & Primary Care, Fac Med, Hong Kong, Hong Kong, Peoples R China.
[Lam, Tommy Tsan-Yuk] Univ Hong Kong, Sch Publ Hlth, Hong Kong, Hong Kong, Peoples R China.
[Wu, Chunli; Zhang, Renli] Shenzhen Ctr Dis Control & Prevent, Shenzhen 518055, Guangdong, Peoples R China.
[Weinberger, Daniel M.] Yale Univ, Sch Publ Hlth, Dept Epidemiol Microbial Dis, New Haven, CT 06520 USA.
RP Tan, Y (reprint author), NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
EM yiyity@gmail.com
RI Lee, Shui Shan/B-9374-2008; Lam, Tommy Tsan-Yuk/D-4837-2012;
OI Lee, Shui Shan/0000-0003-1448-765X; Weinberger,
Daniel/0000-0003-1178-8086
FU International Influenza Unit, Office of Global Affairs, US Department of
Health and Human Services
FX This research was conducted in the context of the MISMS Study, 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). The MISMS study is funded by
the International Influenza Unit, Office of Global Affairs, US
Department of Health and Human Services. The Department of Health, Hong
Kong, is acknowledged for access to the laboratory surveillance data
from Hong Kong. The authors declare no conflicts of interest.
NR 35
TC 2
Z9 2
U1 0
U2 2
PU SOC GENERAL MICROBIOLOGY
PI READING
PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG,
BERKS, ENGLAND
SN 0022-1317
EI 1465-2099
J9 J GEN VIROL
JI J. Gen. Virol.
PD MAR
PY 2014
VL 95
BP 531
EP 538
DI 10.1099/vir.0.059998-0
PN 3
PG 8
WC Biotechnology & Applied Microbiology; Virology
SC Biotechnology & Applied Microbiology; Virology
GA AK1LV
UT WOS:000338177500002
PM 24310518
ER
PT J
AU Hart, BJ
Dyall, J
Postnikova, E
Zhou, HY
Kindrachuk, J
Johnson, RF
Olinger, GG
Frieman, MB
Holbrook, MR
Jahrling, PB
Hensley, L
AF Hart, Brit J.
Dyall, Julie
Postnikova, Elena
Zhou, Huanying
Kindrachuk, Jason
Johnson, Reed F.
Olinger, Gene G., Jr.
Frieman, Matthew B.
Holbrook, Michael R.
Jahrling, Peter B.
Hensley, Lisa
TI Interferon-beta and mycophenolic acid are potent inhibitors of Middle
East respiratory syndrome coronavirus in cell-based assays
SO JOURNAL OF GENERAL VIROLOGY
LA English
DT Article
ID IN-VITRO; C VIRUS; ANTIVIRAL ACTIVITY; IMP DEHYDROGENASE;
CYCLOSPORINE-A; RIBAVIRIN; COV; REPLICATION; ALPHA; VIVO
AB The Middle East respiratory syndrome coronavirus (MERS-CoV) presents a novel emerging threat to public health worldwide. Several treatments for infected individuals have been suggested including IFN, ribavirin and passive immunotherapy with convalescent plasma. Administration of IFN-alpha 2b and ribavirin has improved outcomes of MERS-CoV infection in rhesus macaques when administered within 8 h post-challenge. However, detailed and systematic evidence on the activity of other clinically available drugs is limited. Here we compared the susceptibility of MERS-CoV with different IFN products (IFN-alpha 2b, IFN-gamma, IFN-universal, IFN-alpha 2a and IFN-beta), as well as with two antivirals, ribavirin and mycophenolic acid (MPA), against MERS-CoV (Hu/Jordan-N3/2012) in vitro. Of all the IFNs tested, IFN-beta showed the strongst inhibition of MERS-CoV in vitro, with an IC50 of 1.37 U ml(-1), 41 times lower than the previously reported IC50 (56.08 U ml(-1)) of IFN-alpha 2b. IFN-beta inhibition was confirmed in the virus yield reduction assay, with an IC90 of 38.8 U ml(-1). Ribavirin did not inhibit viral replication in vitro at a dose that would be applicable to current treatment protocols in humans. In contrast, MPA showed strong inhibition, with an IC50 of 2.87 mu M. This drug has not been previously tested against MERS-CoV and may provide an alternative to ribavirin for treatment of MERS-CoV. In conclusion, IFN-beta, MPA or a combination of the two may be beneficial in the treatment of MERS-CoV or as a post-exposure intervention in high-risk patients with known exposures to MERS-CoV.
C1 [Hart, Brit J.; Dyall, Julie; Postnikova, Elena; Zhou, Huanying; Kindrachuk, Jason; Olinger, Gene G., Jr.; Holbrook, Michael R.; Jahrling, Peter B.; Hensley, Lisa] NIAID, Integrated Res Facil, NIH, Frederick, MD 21703 USA.
[Johnson, Reed F.; Jahrling, Peter B.] NIAID, Emerging Viral Pathogens Sect, NIH, Frederick, MD USA.
[Frieman, Matthew B.] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA.
RP Jahrling, PB (reprint author), NIAID, Integrated Res Facil, NIH, Frederick, MD 21703 USA.
EM jahrlingp@niaid.nih.gov
RI Hart, Brit/G-6205-2015
OI Hart, Brit/0000-0002-9389-2786
FU Division of Intramural Research of the National Institute of Allergy and
Infectious Diseases (NIAID); Integrated Research Facility (NIAID,
Division of Clinical Research); Battelle Memorial Institute; NIAID
[HHSN272200700016I]
FX We thank Calli Lear, Yingyun Cai and Cindy Allan for outstanding
assistance in development of the drug screen protocol and Cindy Allan
for implementation of protocols in the biocontainment suite. We thank
cell culture staff in preparing the cells used in this study. In
addition, we acknowledge Laura Bollinger for technical writing services
in preparation of this manuscript and Jiro Wada for figure preparation.
This work was supported by the Division of Intramural Research of the
National Institute of Allergy and Infectious Diseases (NIAID),
Integrated Research Facility (NIAID, Division of Clinical Research) and
Battelle Memorial Institute's prime contract with NIAID (contract no.
HHSN272200700016I). The content of this publication does not necessarily
reflect the views or policies of the US Department of Health and Human
Services or of the institutions and companies affiliated with the
authors. B. J. H., J. D. and E. P. performed this work as employees of
Tunnell Consulting, Inc., a subcontractor to Battelle Memorial
Institute; H. Z. performed this work as an employee of Loveless
Commercial Contracting, Inc., a subcontractor to Battelle Memorial
Institute; G. G. O., Jr performed this work as an employee of Midwest
Research Institute, a subcontractor to Battelle Memorial Institute; and
J. K. and M. R. H. performed this work as employees of Battelle Memorial
Institute, all under its prime contract with NIAID, under contract no.
HHSN272200700016I.
NR 21
TC 29
Z9 31
U1 0
U2 3
PU SOC GENERAL MICROBIOLOGY
PI READING
PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG,
BERKS, ENGLAND
SN 0022-1317
EI 1465-2099
J9 J GEN VIROL
JI J. Gen. Virol.
PD MAR
PY 2014
VL 95
BP 571
EP 577
DI 10.1099/vir.0.061911-0
PN 3
PG 7
WC Biotechnology & Applied Microbiology; Virology
SC Biotechnology & Applied Microbiology; Virology
GA AK1LV
UT WOS:000338177500006
PM 24323636
ER
PT J
AU Nair, SC
Pattaradilokrat, S
Zilversmit, MM
Dommer, J
Nagarajan, V
Stephens, MT
Xiao, WM
Tan, JC
Su, XZ
AF Nair, Sethu C.
Pattaradilokrat, Sittiporn
Zilversmit, Martine M.
Dommer, Jennifer
Nagarajan, Vijayaraj
Stephens, Melissa T.
Xiao, Wenming
Tan, John C.
Su, Xin-zhuan
TI Genome-wide polymorphisms and development of a microarray platform to
detect genetic variations in Plasmodium yoelii
SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY
LA English
DT Article
DE Malaria; Rodent; High-throughput genotyping; Single nucleotide
polymorphism; Genome sequencing
ID RODENT MALARIA PARASITE; DRUG-RESISTANCE; IMMUNE-RESPONSES; FALCIPARUM;
PHENOTYPE; PATHOLOGY; SELECTION; MODELS; MOUSE; MICE
AB The rodent malaria parasite Plasmodium yoelii is an important model for studying malaria immunity and pathogenesis. One approach for studying malaria disease phenotypes is genetic mapping, which requires typing a large number of genetic markers from multiple parasite strains and/or progeny from genetic crosses. Hundreds of microsatellite (MS) markers have been developed to genotype the P. yoelii genome; however, typing a large number of MS markers can be labor intensive, time consuming, and expensive. Thus, development of high-throughput genotyping tools such as DNA microarrays that enable rapid and accurate large-scale genotyping of the malaria parasite will be highly desirable. In this study, we sequenced the genomes of two P. yoelii strains (33X and N67) and obtained a large number of single nucleotide polymorphisms (SNPs). Based on the SNPs obtained, we designed sets of oligonucleotide probes to develop a microarray that could interrogate 11,000 SNPs across the 14 chromosomes of the parasite in a single hybridization. Results from hybridizations of DNA samples of five P. yoelii strains or cloned lines (17XNL, YM, 33X, N67 and N67C) and two progeny from a genetic cross (N67 x 17XNL) to the microarray showed that the array had a high call rate (similar to 97%) and accuracy (99.9%) in calling SNPs, providing a simple and reliable tool for typing the P. yoelii genome. Our data show that the P. yoelii genome is highly polymorphic, although isogenic pairs of parasites were also detected. Additionally, our results indicate that the 33X parasite is a progeny of 17XNL (or YM) and an unknown parasite. The highly accurate and reliable microarray developed in this study will greatly facilitate our ability to study the genetic basis of important traits and the disease it causes. Published by Elsevier B.V.
C1 [Nair, Sethu C.; Pattaradilokrat, Sittiporn; Zilversmit, Martine M.; Su, Xin-zhuan] NIAID, Laboratoty Malaria & Vector Researnh, NIH, Bethesda, MD 20892 USA.
[Pattaradilokrat, Sittiporn] Chulalongkorn Univ, Fac Sci, Dept Biol, Bangkok 10330, Thailand.
[Dommer, Jennifer; Nagarajan, Vijayaraj] NIAID, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, NIH, Bethesda, MD 20892 USA.
[Stephens, Melissa T.; Tan, John C.] Univ Notre Dame, Eck Inst Global Hlth, Dept Biol Sci, Notre Dame, IN 46556 USA.
[Xiao, Wenming] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA.
RP Su, XZ (reprint author), NIAID, Laboratoty Malaria & Vector Researnh, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM xsu@niaid.nih.gov
OI Pattaradilokrat, Sittiporn/0000-0001-8090-6301; Su,
Xinzhuan/0000-0003-3246-3248
FU Intramural Research Program of the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX This work was supported by the Intramural Research Program of the
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health. We thank Brenda Rae
Marshall, DPSS, NIAID, for editing. Because SCN, SP, MZ, JD, VN, WX, and
X-zS are government employees and this is a government work, the work is
in the public domain in the United States. Notwithstanding any other
agreements, the NIH reserves the right to provide the work to
PubMedCentral for display and use by the public, and PubMedCentral may
tag or modify the work consistent with its customary practices. You can
establish rights outside of the U.S. subject to a government use
license.
NR 31
TC 2
Z9 2
U1 0
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-6851
EI 1872-9428
J9 MOL BIOCHEM PARASIT
JI Mol. Biochem. Parasitol.
PD MAR-APR
PY 2014
VL 194
IS 1-2
BP 9
EP 15
DI 10.1016/j.molbiopara.2014.03.006
PG 7
WC Biochemistry & Molecular Biology; Parasitology
SC Biochemistry & Molecular Biology; Parasitology
GA AJ9AR
UT WOS:000337999700002
PM 24685548
ER
PT J
AU Ford, N
Mofenson, L
Shubber, Z
Calmy, A
Andrieux-Meyer, I
Vitoria, M
Shaffer, N
Renaud, F
AF Ford, Nathan
Mofenson, Lynne
Shubber, Zara
Calmy, Alexandra
Andrieux-Meyer, Isabelle
Vitoria, Marco
Shaffer, Nathan
Renaud, Francoise
TI Safety of efavirenz in the first trimester of pregnancy: an updated
systematic review and meta-analysis
SO AIDS
LA English
DT Article
DE birth defects; congenital anomalies; efavirenz; HIV; AIDS; pregnancy;
systematic review; WHO
ID ACTIVE ANTIRETROVIRAL THERAPY; HIV ASSOCIATION GUIDELINES;
CONGENITAL-ABNORMALITIES; INFECTED WOMEN; BIRTH-DEFECTS; EXPOSURE; RISK;
RECOMMENDATIONS; OUTCOMES; INFANTS
AB Introduction:Primate studies and some observational human data have raised concern regarding an association of first-trimester efavirenz exposure with central nervous system congenital anomalies. The objective of this review is to update evidence on efavirenz safety in HIV-infected pregnant women to inform revision of the 2013 WHO guidelines for antiretroviral therapy in low and middle-income countries.Design:A systematic review and meta-analysis.Methods:We searched for studies reporting birth outcomes among women exposed to efavirenz during the first trimester of pregnancy up to 10 January 2014. Relative risks of congenital anomalies comparing women exposed to efavirenz and nonefavirenz-based antiretroviral regimens were pooled using random effects meta-analysis.Results:Twenty-three studies were included in this review, among which 21 reported the birth outcomes of 2026 live births among women exposed to efavirenz during the first trimester of pregnancy. Forty-four congenital anomalies were reported, giving a pooled proportion of 1.63% [95% confidence interval (95% CI) 0.78-2.48], with only one neural tube defect. Twelve studies reported birth outcomes of women exposed to efavirenz or nonefavirenz-containing regimens during the first trimester of pregnancy. Pooled analysis found no differences in overall risks congenital anomalies between these two groups (relative risk 0.78, 95% CI 0.56-1.08). The incidence of neural tube defects was low, 0.05% (95% CI <0.01-0.28), and similar to incidence in the general population.Discussion:This updated analysis found no evidence of an increased risk of overall or central nervous system congenital anomalies associated with first-trimester exposure to efavirenz, similar to previous systematic reviews. This review contributed to the evidence base for the revised 2013 WHO guidelines on antiretroviral therapy, which recommend that efavirenz can be included as part of first-line therapy in adults regardless of sex, and that it can be used throughout pregnancy, including during the first trimester. However, because of the low incidence of central nervous system anomalies in the overall population and relatively small number of exposures in the current literature, continued birth outcomes prospective surveillance is warranted. (C) 2014 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
C1 [Ford, Nathan; Vitoria, Marco; Shaffer, Nathan; Renaud, Francoise] WHO, HIV Dept, CH-1211 Geneva 27, Switzerland.
[Mofenson, Lynne] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Rockville, MD USA.
[Shubber, Zara] Univ London Imperial Coll Sci Technol & Med, Dept Infect Dis Epidemiol, London, England.
[Calmy, Alexandra] Univ Hosp Geneva, HIV AIDS Unit, Infect Dis Serv, Geneva, Switzerland.
[Calmy, Alexandra; Andrieux-Meyer, Isabelle] Med Sans Frontieres, Geneva, Switzerland.
RP Ford, N (reprint author), WHO, HIV Dept, 20 Ave Appia, CH-1211 Geneva 27, Switzerland.
EM fordn@who.int
FU Bill and Melinda Gates Foundation
FX We would like to thank Martina Penazatto for comments on an earlier
draft, and Heather Watts for assisting with access to data from the
Antiretroviral Pregnancy Registry. The review was supported by funds
from the Bill and Melinda Gates Foundation. This manuscript represents
the views of the authors and does not necessarily represent the view of
the National Institutes of Health or Department of Health and Human
Services.
NR 51
TC 24
Z9 25
U1 1
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
EI 1473-5571
J9 AIDS
JI Aids
PD MAR
PY 2014
VL 28
SU 2
BP S123
EP S131
DI 10.1097/QAD.0000000000000231
PG 9
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA AJ4XO
UT WOS:000337683200005
PM 24849471
ER
PT J
AU Siberry, G
Tindyebwa, D
AF Siberry, George
Tindyebwa, Denis
TI Commentary: When to start and what to use in children - recommendations
and rationale
SO AIDS
LA English
DT Article
ID HIV-INFECTED CHILDREN; ANTIRETROVIRAL THERAPY; NEVIRAPINE; TRIAL
C1 [Siberry, George] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal & Pediat Infect Dis MPID Branch, NIH, Bethesda, MD 20892 USA.
[Tindyebwa, Denis] ANECCA, Kampala, Uganda.
RP Siberry, G (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal & Pediat Infect Dis MPID Branch, NIH, 6100 Execut Blvd,Room 4B11H, Bethesda, MD 20892 USA.
EM siberryg@mail.nih.gov
NR 10
TC 2
Z9 2
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
EI 1473-5571
J9 AIDS
JI Aids
PD MAR
PY 2014
VL 28
SU 2
BP S133
EP S135
DI 10.1097/QAD.0000000000000241
PG 3
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA AJ4XO
UT WOS:000337683200006
PM 24849472
ER
PT J
AU Parsons, HM
Harlan, LC
Stevens, JL
Ullmann, CD
AF Parsons, Helen M.
Harlan, Linda C.
Stevens, Jennifer L.
Ullmann, Claudio Dansky
TI Treatment of Small Cell Lung Cancer in Academic and Community Settings
Factors Associated With Receiving Standard Therapy and Survival
SO CANCER JOURNAL
LA English
DT Article
DE small cell; lung cancer; treatment patterns; survival
ID PROPHYLACTIC CRANIAL IRRADIATION; END RESULTS DATABASE; MEDICARE
BENEFICIARIES; UNITED-STATES; OUTCOMES; EPIDEMIOLOGY; SURVEILLANCE;
CHEMOTHERAPY; CARCINOMA; CISPLATIN
AB Purpose: Small cell lung cancer (SCLC) historically has had poor prognosis. Clinical trials have demonstrated improved survival among patients receiving standard platinum-/etoposide-based chemotherapy. Whereas treatment patterns and outcomes have been evaluated for patients with SCLC in clinical trials, population-based practice patterns are not well known.
Methods: The National Cancer Institute's Patterns of Care study was used to evaluate patient and provider factors associated with standard treatment, clinical trial enrollment, and 12-month relative hazard of death.
Results: Among 931 patients with SCLC diagnosed in 2007 in academic and community settings, 72.2% of patients with limited-stage (LS) disease received chemoradiation and 42.2% of patients with extensive-stage (ES) disease received chemotherapy only; the expected treatment scenarios by stage. Less than 1% of the patients enrolled in clinical trials and 2.1% of the patients with LS disease and 3.4% of the patients with ES disease refused any type of treatment. Patients 80 years or older at diagnosis and those with pneumonia/lung collapse were less likely to receive chemoradiation for LS disease. Patients treated in hospitals with residency programs were more likely to receive chemotherapy for ES disease, and patients 80 years or older were less likely to receive chemotherapy for ES disease. Finally, female patients with LS disease, black patients with ES disease, and all patients who received chemotherapy compared to receiving radiation alone or no therapy experienced significantly lower mortality.
Discussion: Despite the demonstrated lower mortality, a relatively large proportion of patients with SCLC are not treated with a standard treatment regimen. Future studies should evaluate efforts to promote use of appropriate treatment regimens and encourage clinical trial participation.
C1 [Parsons, Helen M.; Harlan, Linda C.] NCI, Appl Res Program, Bethesda, MD 20892 USA.
[Stevens, Jennifer L.] Informat Management Serv Inc, Calverton, MD USA.
[Ullmann, Claudio Dansky] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Parsons, HM (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Sch Med, Dept Epidemiol & Biostat, 7703 Floyd Curl Dr,Mail Code 7933, San Antonio, TX 78229 USA.
EM parsonsh@uthscsa.edu
FU National Cancer Institute [HHSN261201000024C, HHSN261201000025C,
HHSN261201000032C, HHSN261201000027C]; National Cancer Institute.
[HHSN261201000026C, HHSN261201000140C, HHSN261201000037C,
HHSN261201000033C, HHSN261201000034C, HHSN261201000035C,
HHSN261201000029C, HHSN261201000031C, HHSN261201000028C,
HHSN261201000030C, K07CA175063]
FX Dr. Parsons receives support from the National Cancer Institute
(K07CA175063).; This work was supported by National Cancer Institute
contracts HHSN261201000024C, HHSN261201000025C, HHSN261201000032C,
HHSN261201000027C, HHSN261201000026C, HHSN261201000140C,
HHSN261201000037C, HHSN261201000033C, HHSN261201000034C,
HHSN261201000035C, HHSN261201000029C, HHSN261201000031C,
HHSN261201000028C, HHSN261201000030C.
NR 30
TC 4
Z9 4
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1528-9117
EI 1540-336X
J9 CANCER J
JI Cancer J.
PD MAR-APR
PY 2014
VL 20
IS 2
BP 97
EP 104
PG 8
WC Oncology
SC Oncology
GA AJ4ZD
UT WOS:000337688200001
PM 24667952
ER
PT J
AU Wassmann, C
AF Wassmann, Claudia
TI "PICTURESQUE INCISIVENESS": EXPLAINING THE CELEBRITY OF JAMES'S THEORY
OF EMOTION
SO JOURNAL OF THE HISTORY OF THE BEHAVIORAL SCIENCES
LA English
DT Article
ID LANGE THEORY; FEELINGS
AB William James is the name that comes to mind when asked about scientific explanations of emotion in the nineteenth century. However, strictly speaking James's theory of emotion does not explain emotions and never did. Indeed, James contemporaries pointed this out already more than a hundred years ago. Why could "James' theory" nevertheless become a landmark that psychologists, neuroscientists, and historians alike refer to today? The strong focus on James and Anglo-American sources in historiography has overshadowed all other answers given to the question of emotion at the time of James. For that reason, the article returns to the primary sources and places James's work back into the context of nineteenth century brain research in which it developed. (C) 2014 Wiley Periodicals, Inc.
C1 [Wassmann, Claudia] Max Planck Inst Human Dev, Ctr Hist Emot, Berlin, Germany.
[Wassmann, Claudia] NIH, Bethesda, MD USA.
RP Wassmann, C (reprint author), Univ Navarra, Inst Culture & Soc, E-31080 Pamplona, Spain.
NR 85
TC 2
Z9 2
U1 2
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-5061
EI 1520-6696
J9 J HIST BEHAV SCI
JI J. Hist. Behav. Sci.
PD SPR
PY 2014
VL 50
IS 2
BP 166
EP 188
DI 10.1002/jhbs.21651
PG 23
WC History Of Social Sciences
SC Social Sciences - Other Topics
GA AI9TL
UT WOS:000337280100003
PM 24615670
ER
PT J
AU Moyes, CL
Henry, AJ
Golding, N
Huang, Z
Singh, B
Baird, JK
Newton, PN
Huffman, M
Duda, KA
Drakeley, CJ
Elyazar, IRF
Anstey, NM
Chen, QJ
Zommers, Z
Bhatt, S
Gething, PW
Hay, SI
AF Moyes, Catherine L.
Henry, Andrew J.
Golding, Nick
Huang, Zhi
Singh, Balbir
Baird, J. Kevin
Newton, Paul N.
Huffman, Michael
Duda, Kirsten A.
Drakeley, Chris J.
Elyazar, Iqbal R. F.
Anstey, Nicholas M.
Chen, Qijun
Zommers, Zinta
Bhatt, Samir
Gething, Peter W.
Hay, Simon I.
TI Defining the Geographical Range of the Plasmodium knowlesi Reservoir
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID ANOPHELES-BALABACENSIS-BALABACENSIS; LONG-TAILED MACAQUE;
MACACA-FASCICULARIS; SIMIAN-MALARIA; HUMAN INFECTIONS; MALAYSIAN-BORNEO;
MONKEY MALARIA; VIVAX MALARIA; P. FALCIPARUM; M-MULATTA
AB Background: The simian malaria parasite, Plasmodium knowlesi, can cause severe and fatal disease in humans yet it is rarely included in routine public health reporting systems for malaria and its geographical range is largely unknown. Because malaria caused by P. knowlesi is a truly neglected tropical disease, there are substantial obstacles to defining the geographical extent and risk of this disease. Information is required on the occurrence of human cases in different locations, on which non-human primates host this parasite and on which vectors are able to transmit it to humans. We undertook a systematic review and ranked the existing evidence, at a subnational spatial scale, to investigate the potential geographical range of the parasite reservoir capable of infecting humans.
Methodology/Principal Findings: After reviewing the published literature we identified potential host and vector species and ranked these based on how informative they are for the presence of an infectious parasite reservoir, based on current evidence. We collated spatial data on parasite occurrence and the ranges of the identified host and vector species. The ranked spatial data allowed us to assign an evidence score to 475 subnational areas in 19 countries and we present the results on a map of the Southeast and South Asia region.
Conclusions/Significance: We have ranked subnational areas within the potential disease range according to evidence for presence of a disease risk to humans, providing geographical evidence to support decisions on prevention, management and prophylaxis. This work also highlights the unknown risk status of large parts of the region. Within this unknown category, our map identifies which areas have most evidence for the potential to support an infectious reservoir and are therefore a priority for further investigation. Furthermore we identify geographical areas where further investigation of putative host and vector species would be highly informative for the region-wide assessment.
C1 [Moyes, Catherine L.; Henry, Andrew J.; Golding, Nick; Huang, Zhi; Duda, Kirsten A.; Bhatt, Samir; Gething, Peter W.; Hay, Simon I.] Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Oxford OX1 3PS, England.
[Singh, Balbir] Univ Malaysia Sarawak, Malaria Res Ctr, Kuching, Sarawak, Malaysia.
[Baird, J. Kevin; Elyazar, Iqbal R. F.] Eijkman Oxford Clin Res Unit, Jakarta, Indonesia.
[Baird, J. Kevin; Newton, Paul N.] Univ Oxford, Ctr Trop Med, Oxford, England.
[Newton, Paul N.] Mahosot Hosp, Microbiol Lab, Wellcome Trust Res Unit, Lao Oxford Mahosot Hosp, Viangchan, Laos.
[Huffman, Michael] Kyoto Univ, Primate Res Inst, Inuyama, Aichi 484, Japan.
[Drakeley, Chris J.] London Sch Hyg & Trop Med, Fac Infect & Trop Dis, Dept Immunol & Infect, London WC1, England.
[Anstey, Nicholas M.] Menzies Sch Hlth Res, Global & Trop Hlth Div, Darwin, NT, Australia.
[Chen, Qijun] Chinese Acad Med Sci, Inst Pathogen Biol, Beijing 100730, Peoples R China.
[Chen, Qijun] Jilin Univ, Key Lab Zoonosis, Changchun 130023, Peoples R China.
[Zommers, Zinta] United Nations Environm Programme, Div Early Warning & Assessment, Nairobi, Kenya.
[Hay, Simon I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Moyes, CL (reprint author), Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, S Parks Rd, Oxford OX1 3PS, England.
EM catherine.moyes@zoo.ox.ac.uk
RI Hay, Simon/F-8967-2015;
OI Hay, Simon/0000-0002-0611-7272; Singh, Balbir/0000-0002-9143-3965;
Golding, Nick/0000-0001-8916-5570; Gething, Peter/0000-0001-6759-5449;
Moyes, Catherine/0000-0002-8028-4079
FU Wellcome Trust [091835, B9RZGS0, 095066]; Bill & Melinda Gates
Foundation [OPP1053338, OPP1068048]; Vector-Borne Disease Network;
Wellcome Trust of Great Britain; Asia Africa Science Platform Program of
the Japan Society for the Promotion of Science; Japanese Ministry of
Education Science; ESEI/UKRC programme grant on Plasmodium knowlesi
[G1100796]; National Health and Medical Research Council Practitioner
Fellowship; RAPIDD program of the Science & Technology Directorate,
Department of Homeland Security; Fogarty International Center, National
Institutes of Health
FX CLM and AJH are supported by the Wellcome Trust [091835]. NG is funded
by a Bill & Melinda Gates Foundation grant [OPP1053338]. ZH is funded by
the Vector-Borne Disease Network. PNN is funded by the Wellcome Trust of
Great Britain. MH is funded by the Asia Africa Science Platform Program
of the Japan Society for the Promotion of Science and Grants-In-Aid for
Overseas Research, Japanese Ministry of Education Science awarded to
Shusuke Nakazawa. CJD is funded by a ESEI/UKRC programme grant on
Plasmodium knowlesi [G1100796]. IRFE is supported by a Wellcome Trust
Research Training Fellowship [B9RZGS0]. NMA is supported by a National
Health and Medical Research Council Practitioner Fellowship. PWG is a
Medical Research Council Career Development Fellow [K00669X] and
receives support from the Bill and Melinda Gates Foundation [OPP1068048]
that also supports SB. SIH is funded by a Senior Research Fellowship
from the Wellcome Trust that also supports KAD [095066]. SIH also
acknowledges support from the RAPIDD program of the Science & Technology
Directorate, Department of Homeland Security, and the Fogarty
International Center, National Institutes of Health
(http://www.fic.nih.gov). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 91
TC 23
Z9 23
U1 6
U2 28
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1935-2735
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD MAR
PY 2014
VL 8
IS 3
AR e2780
DI 10.1371/journal.pntd.0002780
PG 13
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA AJ0MU
UT WOS:000337348800043
PM 24676231
ER
PT J
AU Zahedifard, F
Gholami, E
Taheri, T
Taslimi, Y
Doustdari, F
Seyed, N
Torkashvand, F
Meneses, C
Papadopoulou, B
Kamhawi, S
Valenzuela, JG
Rafati, S
AF Zahedifard, Farnaz
Gholami, Elham
Taheri, Tahereh
Taslimi, Yasaman
Doustdari, Fatemeh
Seyed, Negar
Torkashvand, Fatemeh
Meneses, Claudio
Papadopoulou, Barbara
Kamhawi, Shaden
Valenzuela, Jesus G.
Rafati, Sima
TI Enhanced Protective Efficacy of Nonpathogenic Recombinant Leishmania
tarentolae Expressing Cysteine Proteinases Combined with a Sand Fly
Salivary Antigen
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID VISCERAL LEISHMANIASIS; VACCINE CANDIDATES; MICE; GENE; CHALLENGE;
IMMUNITY; VECTOR; CELLS; STAGE
AB Background: Novel vaccination approaches are needed to prevent leishmaniasis. Live attenuated vaccines are the gold standard for protection against intracellular pathogens such as Leishmania and there have been new developments in this field. The nonpathogenic to humans lizard protozoan parasite, Leishmania (L) tarentolae, has been used effectively as a vaccine platform against visceral leishmaniasis in experimental animal models. Correspondingly, pre-exposure to sand fly saliva or immunization with a salivary protein has been shown to protect mice against cutaneous leishmaniasis.
Methodology/Principal Findings: Here, we tested the efficacy of a novel combination of established protective parasite antigens expressed by L. tarentolae together with a sand fly salivary antigen as a vaccine strategy against L. major infection. The immunogenicity and protective efficacy of different DNA/Live and Live/Live prime-boost vaccination modalities with live recombinant L. tarentolae stably expressing cysteine proteinases (type I and II, CPA/CPB) and PpSP15, an immunogenic salivary protein from Phlebotomus papatasi, a natural vector of L. major, were tested both in susceptible BALB/c and resistant C57BL/6 mice. Both humoral and cellular immune responses were assessed before challenge and at 3 and 10 weeks after Leishmania infection. In both strains of mice, the strongest protective effect was observed when priming with PpSP15 DNA and boosting with PpSP15 DNA and live recombinant L. tarentolae stably expressing cysteine proteinase genes.
Conclusion/Significance: The present study is the first to use a combination of recombinant L. tarentolae with a sand fly salivary antigen (PpSP15) and represents a novel promising vaccination approach against leishmaniasis.
C1 [Zahedifard, Farnaz; Gholami, Elham; Taheri, Tahereh; Taslimi, Yasaman; Doustdari, Fatemeh; Seyed, Negar; Rafati, Sima] Pasteur Inst Iran, Mol Immunol & Vaccine Res Lab, Tehran, Iran.
[Torkashvand, Fatemeh] Pasteur Inst Iran, Biotechnol Res Ctr, Tehran, Iran.
[Meneses, Claudio; Kamhawi, Shaden; Valenzuela, Jesus G.] NIAID, Vector Mol Biol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
[Papadopoulou, Barbara] Univ Laval, CHUL Res Ctr, CHU Quebec Res Ctr, Res Ctr Infect Dis, Quebec City, PQ, Canada.
[Papadopoulou, Barbara] Univ Laval, Dept Microbiol Infect Dis & Immunol, Quebec City, PQ, Canada.
RP Zahedifard, F (reprint author), Pasteur Inst Iran, Mol Immunol & Vaccine Res Lab, Tehran, Iran.
EM s_rafati@yahoo.com
FU CRDF [INB2-7015-TN-10]; Pasteur Institute of Iran; Intramural Research
Program, NIAID, NIH
FX This project received financial support from CRDF (award number
INB2-7015-TN-10) and Pasteur Institute of Iran. The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript. This work (JGV, SK) was supported in part
by the Intramural Research Program, NIAID, NIH.
NR 36
TC 19
Z9 19
U1 2
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1935-2735
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD MAR
PY 2014
VL 8
IS 3
AR e2751
DI 10.1371/journal.pntd.0002751
PG 14
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA AJ0MU
UT WOS:000337348800033
PM 24675711
ER
PT J
AU Chiu, C
McCausland, M
Sidney, J
Duh, FM
Rouphael, N
Mehta, A
Mulligan, M
Carrington, M
Wieland, A
Sullivan, NL
Weinberg, A
Levin, MJ
Pulendran, B
Peters, B
Sette, A
Ahmed, R
AF Chiu, Christopher
McCausland, Megan
Sidney, John
Duh, Fuh-Mei
Rouphael, Nadine
Mehta, Aneesh
Mulligan, Mark
Carrington, Mary
Wieland, Andreas
Sullivan, Nicole L.
Weinberg, Adriana
Levin, Myron J.
Pulendran, Bali
Peters, Bjoern
Sette, Alessandro
Ahmed, Rafi
TI Broadly Reactive Human CD8 T Cells that Recognize an Epitope Conserved
between VZV, HSV and EBV
SO PLOS PATHOGENS
LA English
DT Article
ID VARICELLA-ZOSTER-VIRUS; HERPES-SIMPLEX VIRUSES; EPSTEIN-BARR-VIRUS;
IMMUNE EVASION; VACCINE; INFECTION; RESPONSES; ANTIGENS; DELETION
AB Human herpesviruses are important causes of potentially severe chronic infections for which T cells are believed to be necessary for control. In order to examine the role of virus-specific CD8 T cells against Varicella Zoster Virus (VZV), we generated a comprehensive panel of potential epitopes predicted in silico and screened for T cell responses in healthy VZV seropositive donors. We identified a dominant HLA-A*0201-restricted epitope in the VZV ribonucleotide reductase subunit 2 and used a tetramer to analyze the phenotype and function of epitope-specific CD8 T cells. Interestingly, CD8 T cells responding to this VZV epitope also recognized homologous epitopes, not only in the other alpha-herpesviruses, HSV-1 and HSV-2, but also the gamma-herpesvirus, EBV. Responses against these epitopes did not depend on previous infection with the originating virus, thus indicating the cross-reactive nature of this T cell population. Between individuals, the cells demonstrated marked phenotypic heterogeneity. This was associated with differences in functional capacity related to increased inhibitory receptor expression (including PD-1) along with decreased expression of co-stimulatory molecules that potentially reflected their stimulation history. Vaccination with the live attenuated Zostavax vaccine did not efficiently stimulate a proliferative response in this epitope-specific population. Thus, we identified a human CD8 T cell epitope that is conserved in four clinically important herpesviruses but that was poorly boosted by the current adult VZV vaccine. We discuss the concept of a "pan-herpesvirus" vaccine that this discovery raises and the hurdles that may need to be overcome in order to achieve this.
C1 [Chiu, Christopher; McCausland, Megan; Wieland, Andreas; Sullivan, Nicole L.; Pulendran, Bali; Ahmed, Rafi] Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA.
[Chiu, Christopher; McCausland, Megan; Wieland, Andreas; Sullivan, Nicole L.; Ahmed, Rafi] Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA.
[Chiu, Christopher] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Ctr Resp Infect, London, England.
[Sidney, John; Peters, Bjoern; Sette, Alessandro] La Jolla Inst Allergy & Immunol, Div Vaccine Discovery, La Jolla, CA USA.
[Duh, Fuh-Mei; Carrington, Mary] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD USA.
[Duh, Fuh-Mei; Carrington, Mary] MIT & Harvard, Ragon Inst MGH, Cambridge, MA USA.
[Rouphael, Nadine; Mulligan, Mark] Emory Univ, Sch Med, Emory Vaccine Ctr, Hope Clin, Atlanta, GA USA.
[Rouphael, Nadine; Mehta, Aneesh; Mulligan, Mark] Emory Univ, Sch Med, Div Infect Dis, Atlanta, GA USA.
[Weinberg, Adriana; Levin, Myron J.] Univ Colorado, Dept Pediat, Aurora, CO USA.
[Weinberg, Adriana; Levin, Myron J.] Univ Colorado, Dept Med, Aurora, CO USA.
[Weinberg, Adriana; Levin, Myron J.] Univ Colorado, Dept Pathol, Aurora, CO USA.
RP Chiu, C (reprint author), Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA.
EM c.chiu@imperial.ac.uk; rahmed@emory.edu
RI Mehta, Aneesh/B-8054-2012
OI Mehta, Aneesh/0000-0002-6552-9162
FU NIH/NIAID [U19-A1057266, U19-A1090023-01]; Cooperative Centers for
Translational Research on Human Immunology and Biodefense (CCHI) grant
[U19-AI05726]; Frederick National Laboratory for Cancer Research
[HHSN261200800001E]; Intramural Research Program of the NIH, Frederick
National Lab, Center for Cancer Research; Medical Research Council, UK
[G0902266]; Irvington Institute Fellowship Program of the Cancer
Research Institute
FX This work was in part funded by NIH/NIAID U19-A1057266, NIH/NIAID
U19-A1090023-01 (RA), Cooperative Centers for Translational Research on
Human Immunology and Biodefense (CCHI) grant U19-AI05726, with federal
funds from the Frederick National Laboratory for Cancer Research, under
Contract No. HHSN261200800001E, and by the Intramural Research Program
of the NIH, Frederick National Lab, Center for Cancer Research. CC is
funded by the Medical Research Council, UK (G0902266). NLS was supported
by the Irvington Institute Fellowship Program of the Cancer Research
Institute. The content of this publication does not necessarily reflect
the views or policies of the Department of Health and Human Services,
nor does mention of trade names, commercial products, or organizations
imply endorsement by the U.S. Government. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 31
TC 11
Z9 11
U1 0
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD MAR
PY 2014
VL 10
IS 3
AR e1004008
DI 10.1371/journal.ppat.1004008
PG 12
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA AJ2FF
UT WOS:000337470300050
PM 24675761
ER
PT J
AU Cirelli, KM
Gorfu, G
Hassan, MA
Printz, M
Crown, D
Leppla, SH
Grigg, ME
Saeij, JPJ
Moayeri, M
AF Cirelli, Kimberly M.
Gorfu, Gezahegn
Hassan, Musa A.
Printz, Morton
Crown, Devorah
Leppla, Stephen H.
Grigg, Michael E.
Saeij, Jeroen P. J.
Moayeri, Mahtab
TI Inflammasome Sensor NLRP1 Controls Rat Macrophage Susceptibility to
Toxoplasma gondii
SO PLOS PATHOGENS
LA English
DT Article
ID RECOMBINANT INBRED STRAINS; HOST-CELL SUBVERSION; CASPASE-1 ACTIVATION;
MURINE MACROPHAGES; PROTEASES; PARASITE; ANTHRAX; EXPRESSION; RECEPTORS;
INFECTION
AB Toxoplasma gondii is an intracellular parasite that infects a wide range of warm-blooded species. Rats vary in their susceptibility to this parasite. The Toxo1 locus conferring Toxoplasma resistance in rats was previously mapped to a region of chromosome 10 containing Nlrp1. This gene encodes an inflammasome sensor controlling macrophage sensitivity to anthrax lethal toxin (LT) induced rapid cell death (pyroptosis). We show here that rat strain differences in Toxoplasma infected macrophage sensitivity to pyroptosis, IL-1 beta/IL-18 processing, and inhibition of parasite proliferation are perfectly correlated with NLRP1 sequence, while inversely correlated with sensitivity to anthrax LT-induced cell death. Using recombinant inbred rats, SNP analyses and whole transcriptome gene expression studies, we narrowed the candidate genes for control of Toxoplasma-mediated rat macrophage pyroptosis to four genes, one of which was Nlrp1. Knockdown of Nlrp1 in pyroptosis-sensitive macrophages resulted in higher parasite replication and protection from cell death. Reciprocally, overexpression of the NLRP1 variant from Toxoplasma-sensitive macrophages in pyroptosis-resistant cells led to sensitization of these resistant macrophages. Our findings reveal Toxoplasma as a novel activator of the NLRP1 inflammasome in rat macrophages.
C1 [Cirelli, Kimberly M.; Hassan, Musa A.; Saeij, Jeroen P. J.] MIT, Dept Biol, Cambridge, MA 02139 USA.
[Gorfu, Gezahegn; Grigg, Michael E.] NIAID, Mol Parasitol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Printz, Morton] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA.
[Crown, Devorah; Leppla, Stephen H.; Moayeri, Mahtab] NIAID, Microbial Pathogenesis Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Cirelli, KM (reprint author), MIT, Dept Biol, Cambridge, MA 02139 USA.
EM griggm@niaid.nih.gov; jsaeij@mit.edu; mmoayeri@niaid.nih.gov
RI Hassan, Musa/E-8324-2016;
OI Hassan, Musa/0000-0002-0371-3300; Saeij, Jeroen/0000-0003-0289-7109
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases; National Institutes of Health [F31-AI104170,
R01-AI080621]; Wellcome Trust-MIT postdoctoral fellowship
FX This research was supported in part by the Intramural Research Program
of the National Institute of Allergy and Infectious Diseases. KMC was
supported by National Institutes of Health (F31-AI104170), MAH by a
Wellcome Trust-MIT postdoctoral fellowship, and JPJS by National
Institutes of Health (R01-AI080621. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 42
TC 25
Z9 26
U1 1
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD MAR
PY 2014
VL 10
IS 3
AR e1003927
DI 10.1371/journal.ppat.1003927
PG 11
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA AJ2FF
UT WOS:000337470300008
PM 24626226
ER
PT J
AU de Wit, E
Prescott, J
Falzarano, D
Bushmaker, T
Scott, D
Feldmann, H
Munster, VJ
AF de Wit, Emmie
Prescott, Joseph
Falzarano, Darryl
Bushmaker, Trenton
Scott, Dana
Feldmann, Heinz
Munster, Vincent J.
TI Foodborne Transmission of Nipah Virus in Syrian Hamsters
SO PLOS PATHOGENS
LA English
DT Article
ID CENTRAL-NERVOUS-SYSTEM; FLYING-FOXES; BANGLADESH; PARAMYXOVIRUS;
INFECTION; MALAYSIA; ROUTE; MODEL; BATS
AB Since 2001, outbreaks of Nipah virus have occurred almost every year in Bangladesh with high case-fatality rates. Epidemiological data suggest that in Bangladesh, Nipah virus is transmitted from the natural reservoir, fruit bats, to humans via consumption of date palm sap contaminated by bats, with subsequent human-to-human transmission. To experimentally investigate this epidemiological association between drinking of date palm sap and human cases of Nipah virus infection, we determined the viability of Nipah virus (strain Bangladesh/200401066) in artificial palm sap. At 22 degrees C virus titers remained stable for at least 7 days, thus potentially allowing food-borne transmission. Next, we modeled food-borne Nipah virus infection by supplying Syrian hamsters with artificial palm sap containing Nipah virus. Drinking of 5 x 10(8) TCID50 of Nipah virus resulted in neurological disease in 5 out of 8 hamsters, indicating that food-borne transmission of Nipah virus can indeed occur. In comparison, intranasal (i.n.) inoculation with the same dose of Nipah virus resulted in lethal respiratory disease in all animals. In animals infected with Nipah virus via drinking, virus was detected in respiratory tissues rather than in the intestinal tract. Using fluorescently labeled Nipah virus particles, we showed that during drinking, a substantial amount of virus is deposited in the lungs, explaining the replication of Nipah virus in the respiratory tract of these hamsters. Besides the ability of Nipah virus to infect hamsters via the drinking route, Syrian hamsters infected via that route transmitted the virus through direct contact with naive hamsters in 2 out of 24 transmission pairs. Although these findings do not directly prove that date palm sap contaminated with Nipah virus by bats is the origin of Nipah virus outbreaks in Bangladesh, they provide the first experimental support for this hypothesis. Understanding the Nipah virus transmission cycle is essential for preventing and mitigating future outbreaks.
C1 [de Wit, Emmie; Prescott, Joseph; Falzarano, Darryl; Bushmaker, Trenton; Feldmann, Heinz; Munster, Vincent J.] NIAID, Virol Lab, NIH, Hamilton, MT 59840 USA.
[Feldmann, Heinz] NIAID, Rocky Mt Vet Branch, NIH, Hamilton, MT USA.
[Feldmann, Heinz] Univ Manitoba, Dept Med Microbiol, Winnipeg, MB, Canada.
RP de Wit, E (reprint author), NIAID, Virol Lab, NIH, Hamilton, MT 59840 USA.
EM emmie.dewit@nih.gov; vincent.munster@nih.gov
OI de Wit, Emmie/0000-0002-9763-7758; Munster, Vincent/0000-0002-2288-3196
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, 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 26
TC 13
Z9 13
U1 0
U2 20
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD MAR
PY 2014
VL 10
IS 3
AR e1004001
DI 10.1371/journal.ppat.1004001
PG 10
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA AJ2FF
UT WOS:000337470300044
PM 24626480
ER
PT J
AU Kearney, MF
Spindler, J
Shao, W
Yu, S
Anderson, EM
O'Shea, A
Rehm, C
Poethke, C
Kovacs, N
Mellors, JW
Coffin, JM
Maldarelli, F
AF Kearney, Mary F.
Spindler, Jonathan
Shao, Wei
Yu, Sloane
Anderson, Elizabeth M.
O'Shea, Angeline
Rehm, Catherine
Poethke, Carry
Kovacs, Nicholas
Mellors, John W.
Coffin, John M.
Maldarelli, Frank
TI Lack of Detectable HIV-1 Molecular Evolution during Suppressive
Antiretroviral Therapy
SO PLOS PATHOGENS
LA English
DT Article
ID VIRUS TYPE-1 VIREMIA; LOW-LEVEL VIREMIA; CD4(+) T-CELLS; RALTEGRAVIR
INTENSIFICATION; DRUG-RESISTANCE; LYMPHOID-TISSUE; INFECTED INDIVIDUALS;
RESIDUAL VIREMIA; PLASMA VIREMIA; REPLICATION
AB A better understanding of changes in HIV-1 population genetics with combination antiretroviral therapy (cART) is critical for designing eradication strategies. We therefore analyzed HIV-1 genetic variation and divergence in patients' plasma before cART, during suppression on cART, and after viral rebound. Single-genome sequences of plasma HIV-1 RNA were obtained from HIV-1 infected patients prior to cART (N = 14), during suppression on cART (N = 14) and/or after viral rebound following interruption of cART (N = 5). Intra-patient population diversity was measured by average pairwise difference (APD). Population structure was assessed by phylogenetic analyses and a test for panmixia. Measurements of intra-population diversity revealed no significant loss of overall genetic variation in patients treated for up to 15 years with cART. A test for panmixia, however, showed significant changes in population structure in 2/10 patients after short-term cART (<1 year) and in 7/10 patients after long-term cART (1-15 years). The changes consisted of diverse sets of viral variants prior to cART shifting to populations containing one or more genetically uniform subpopulations during cART. Despite these significant changes in population structure, rebound virus after long-term cART had little divergence from pretherapy virus, implicating long-lived cells infected before cART as the source for rebound virus. The appearance of genetically uniform virus populations and the lack of divergence after prolonged cART and cART interruption provide strong evidence that HIV-1 persists in long-lived cells infected before cART was initiated, that some of these infected cells may be capable of proliferation, and that on-going cycles of viral replication are not evident.
C1 [Kearney, Mary F.; Spindler, Jonathan; Yu, Sloane; Anderson, Elizabeth M.; Poethke, Carry; Kovacs, Nicholas; Maldarelli, Frank] NCI, HIV Drug Resistance Program 1, Ctr Canc Res, Frederick, MD 21701 USA.
[Shao, Wei] SAIC, Adv Biomed Comp Ctr, Frederick, MD USA.
[O'Shea, Angeline; Rehm, Catherine] NIAID, Immunoregulat Lab, NIH Bethesda, Bethesda, MD USA.
[Mellors, John W.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA.
[Coffin, John M.] Tufts Univ, Dept Mol Biol & Microbiol, Boston, MA 02111 USA.
RP Kearney, MF (reprint author), NCI, HIV Drug Resistance Program 1, Ctr Canc Res, Frederick, MD 21701 USA.
EM kearneym@ncifcrf.gov
FU Federal funds from the National Cancer Institute, NIH; FM Kirby
Foundation; National Cancer Institute (SAIC) [25XS119]
FX Funding for this research was provided with Federal funds from the
National Cancer Institute, NIH. JMC was a Research Professor of the
American Cancer Society, with support from the FM Kirby Foundation.
Supported in part (JWM) by funding from the National Cancer Institute
(SAIC contract 25XS119). 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. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 42
TC 50
Z9 51
U1 1
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD MAR
PY 2014
VL 10
IS 3
AR e1004010
DI 10.1371/journal.ppat.1004010
PG 14
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA AJ2FF
UT WOS:000337470300051
PM 24651464
ER
PT J
AU Klase, Z
Yedavalli, VSRK
Houzet, L
Perkins, M
Maldarelli, F
Brenchley, J
Strebel, K
Liu, P
Jeang, KT
AF Klase, Zachary
Yedavalli, Venkat S. R. K.
Houzet, Laurent
Perkins, Molly
Maldarelli, Frank
Brenchley, Jason
Strebel, Klaus
Liu, Paul
Jeang, Kuan-Teh
TI Activation of HIV-1 from Latent Infection via Synergy of RUNX1 Inhibitor
Ro5-3335 and SAHA
SO PLOS PATHOGENS
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL DIFFERENTIATION; TAT ANTAGONIST;
TRANSCRIPTION INITIATION; MOLECULAR-BASIS; CBF-BETA; GENE; EXPRESSION;
PROTEINS; PHOSPHORYLATION
AB A major barrier to the elimination of HIV-1 infection is the presence of a pool of long-lived, latently infected CD4+ memory T-cells. The search for treatments to re-activate latent HIV to aid in clearance is hindered by the incomplete understanding of the mechanisms that lead to transcriptional silencing of viral gene expression in host cells. Here we identify a previously unknown role for RUNX1 in HIV-1 transcriptional latency. The RUNX proteins, in combination with the co-factor CBF-beta, are critical transcriptional regulators in T-cells. RUNX1 strongly modulates CD4 expression and contributes to CD4+ T-cell function. We show that RUNX1 can bind DNA sequences within the HIV-1 LTR and that this binding represses transcription. Using patient samples we show a negative correlation between RUNX1 expression and viral load. Furthermore, we find that pharmacologic inhibition of RUNX1 by a small molecule inhibitor, Ro5-3335, synergizes with the histone deacetylase (HDAC) inhibitor SAHA (Vorinostat) to enhance the activation of latent HIV-1 in both cell lines and PBMCs from patients. Our findings indicate that RUNX1 and CBF-beta cooperate in cells to modulate HIV-1 replication, identifying for the first time RUNX1 as a cellular factor involved in HIV-1 latency. This work highlights the therapeutic potential of inhibitors of RUNX1 to reactivate virus and aid in clearance of HIV-1.
C1 [Klase, Zachary; Yedavalli, Venkat S. R. K.; Houzet, Laurent; Perkins, Molly; Brenchley, Jason; Strebel, Klaus; Jeang, Kuan-Teh] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Maldarelli, Frank] NCI, Host Virus Interact Branch, NIH, Bethesda, MD 20892 USA.
[Liu, Paul] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
RP Klase, Z (reprint author), NIAID, Mol Microbiol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM klaseza@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases, NIH; National
Human Genome Research Institute, NIH; Intramural AIDS Targeted Antiviral
Program from the Office of the Director, NIH; Office of AIDS Research,
NIH
FX This work was supported by the intramural research programs of National
Institute of Allergy and Infectious Diseases and National Human Genome
Research Institute, NIH, and by the Intramural AIDS Targeted Antiviral
Program from the Office of the Director, NIH. ZK was supported by a
fellowship from the Office of AIDS Research, NIH. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 50
TC 12
Z9 12
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD MAR
PY 2014
VL 10
IS 3
AR e1003997
DI 10.1371/journal.ppat.1003997
PG 12
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA AJ2FF
UT WOS:000337470300040
PM 24651404
ER
PT J
AU Labo, N
Miley, W
Marshall, V
Gillette, W
Esposito, D
Bess, M
Turano, A
Uldrick, T
Polizzotto, MN
Wyvill, KM
Bagni, R
Yarchoan, R
Whitby, D
AF Labo, Nazzarena
Miley, Wendell
Marshall, Vickie
Gillette, William
Esposito, Dominic
Bess, Matthew
Turano, Alexandra
Uldrick, Thomas
Polizzotto, Mark N.
Wyvill, Kathleen M.
Bagni, Rachel
Yarchoan, Robert
Whitby, Denise
TI Heterogeneity and Breadth of Host Antibody Response to KSHV Infection
Demonstrated by Systematic Analysis of the KSHV Proteome
SO PLOS PATHOGENS
LA English
DT Article
ID SARCOMA-ASSOCIATED HERPESVIRUS; MULTICENTRIC CASTLEMAN DISEASE;
HUMAN-IMMUNODEFICIENCY-VIRUS; EPSTEIN-BARR-VIRUS; KAPOSIS-SARCOMA;
HUMAN-HERPESVIRUS-8 INFECTION; RISK-FACTORS; SEROLOGIC ASSAYS; ORF59
PROTEIN; DNA-SEQUENCES
AB The Kaposi sarcoma associated herpesvirus (KSHV) genome encodes more than 85 open reading frames (ORFs). Serological evaluation of KSHV infection now generally relies on reactivity to just one latent and/or one lytic protein (commonly ORF73 and K8.1). Most of the other polypeptides encoded by the virus have unknown antigenic profiles. We have systematically expressed and purified products from 72 KSHV ORFs in recombinant systems and analyzed seroreactivity in US patients with KSHV-associated malignancies, and US blood donors (low KSHV seroprevalence population). We identified several KSHV proteins (ORF38, ORF61, ORF59 and K5) that elicited significant responses in individuals with KSHV-associated diseases. In these patients, patterns of reactivity were heterogeneous; however, HIV infection appeared to be associated with breadth and intensity of serological responses. Improved antigenic characterization of additional ORFs may increase the sensitivity of serologic assays, lead to more rapid progresses in understanding immune responses to KSHV, and allow for better comprehension of the natural history of KSHV infection. To this end, we have developed a bead-based multiplex assay detecting antibodies to six KSHV antigens.
C1 [Labo, Nazzarena; Miley, Wendell; Marshall, Vickie; Whitby, Denise] Frederick Natl Lab Canc Res, Viral Oncol Sect, AIDS & Canc Virus Program, Frederick, MD 21702 USA.
[Labo, Nazzarena] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Gillette, William; Esposito, Dominic; Bess, Matthew; Turano, Alexandra; Bagni, Rachel] Frederick Natl Lab Canc Res, Prot Express Lab, Adv Technol Program, Frederick, MD USA.
[Uldrick, Thomas; Polizzotto, Mark N.; Wyvill, Kathleen M.; Yarchoan, Robert] NCI, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA.
RP Labo, N (reprint author), Frederick Natl Lab Canc Res, Viral Oncol Sect, AIDS & Canc Virus Program, Frederick, MD 21702 USA.
EM whitbyd@mail.nih.gov
RI Labo, Nazzarena/H-8655-2012
OI Labo, Nazzarena/0000-0001-5953-4064
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX This project has been funded with federal funds from the National Cancer
Institute, National Institutes of Health, under Contract No.
HHSN261200800001E and the Intramural Research Program. The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 51
TC 8
Z9 8
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD MAR
PY 2014
VL 10
IS 3
AR e1004046
DI 10.1371/journal.ppat.1004046
PG 11
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA AJ2FF
UT WOS:000337470300068
PM 24675986
ER
PT J
AU Lakdawala, SS
Wu, YC
Wawrzusin, P
Kabat, J
Broadbent, AJ
Lamirande, EW
Fodor, E
Altan-Bonnet, N
Shroff, H
Subbarao, K
AF Lakdawala, Seema S.
Wu, Yicong
Wawrzusin, Peter
Kabat, Juraj
Broadbent, Andrew J.
Lamirande, Elaine W.
Fodor, Ervin
Altan-Bonnet, Nihal
Shroff, Hari
Subbarao, Kanta
TI Influenza A Virus Assembly Intermediates Fuse in the Cytoplasm
SO PLOS PATHOGENS
LA English
DT Article
ID PROTEIN-PROTEIN INTERACTIONS; GENOMIC RNA SEGMENTS; SINGLE AMINO-ACID;
PA SUBUNIT; HOST-RANGE; RIBONUCLEOPROTEIN COMPLEXES; NUCLEAR EXPORT;
IN-VIVO; VISUALIZATION; TRANSMISSION
AB Reassortment of influenza viral RNA (vRNA) segments in co-infected cells can lead to the emergence of viruses with pandemic potential. Replication of influenza vRNA occurs in the nucleus of infected cells, while progeny virions bud from the plasma membrane. However, the intracellular mechanics of vRNA assembly into progeny virions is not well understood. Here we used recent advances in microscopy to explore vRNA assembly and transport during a productive infection. We visualized four distinct vRNA segments within a single cell using fluorescent in situ hybridization (FISH) and observed that foci containing more than one vRNA segment were found at the external nuclear periphery, suggesting that vRNA segments are not exported to the cytoplasm individually. Although many cytoplasmic foci contain multiple vRNA segments, not all vRNA species are present in every focus, indicating that assembly of all eight vRNA segments does not occur prior to export from the nucleus. To extend the observations made in fixed cells, we used a virus that encodes GFP fused to the viral polymerase acidic (PA) protein (WSN PA-GFP) to explore the dynamics of vRNA assembly in live cells during a productive infection. Since WSN PA-GFP colocalizes with viral nucleoprotein and influenza vRNA segments, we used it as a surrogate for visualizing vRNA transport in 3D and at high speed by inverted selective-plane illumination microscopy. We observed cytoplasmic PA-GFP foci colocalizing and traveling together en route to the plasma membrane. Our data strongly support a model in which vRNA segments are exported from the nucleus as complexes that assemble en route to the plasma membrane through dynamic colocalization events in the cytoplasm.
C1 [Lakdawala, Seema S.; Broadbent, Andrew J.; Lamirande, Elaine W.; Subbarao, Kanta] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Wu, Yicong; Wawrzusin, Peter; Shroff, Hari] Natl Inst Biomed Imaging & Bioengn, Sect High Resolut Opt Imaging, NIH, Bethesda, MD USA.
[Kabat, Juraj] NIAID, Res Technol Branch, NIH, Bethesda, MD 20892 USA.
[Fodor, Ervin] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England.
[Altan-Bonnet, Nihal] NHLBI, Lab Host Pathogen Dynam, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA.
RP Lakdawala, SS (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
EM Seema.Lakdawala@nih.gov; Hari.Shroff@nih.gov
RI Shroff, Hari/E-7247-2016;
OI Shroff, Hari/0000-0003-3613-8215; Broadbent, Andrew/0000-0002-4716-1835
FU Division of Intramural Research of NIAID, NIH; Intramural Research
Program of the NIH National Institute of Biomedical Imaging and
Bioengineering
FX This research was supported in part by the Division of Intramural
Research of NIAID, NIH, and the Intramural Research Program of the NIH
National Institute of Biomedical Imaging and Bioengineering. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 52
TC 24
Z9 25
U1 3
U2 13
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD MAR
PY 2014
VL 10
IS 3
AR e1003971
DI 10.1371/journal.ppat.1003971
PG 11
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA AJ2FF
UT WOS:000337470300025
PM 24603687
ER
PT J
AU Le Saout, C
Hasley, RB
Imamichi, H
Tcheung, L
Hu, ZH
Luckey, MA
Park, JH
Durum, SK
Smith, M
Rupert, AW
Sneller, MC
Lane, HC
Catalfamo, M
AF Le Saout, Cecile
Hasley, Rebecca B.
Imamichi, Hiromi
Tcheung, Lueng
Hu, Zonghui
Luckey, Megan A.
Park, Jung-Hyun
Durum, Scott K.
Smith, Mindy
Rupert, Adam W.
Sneller, Michael C.
Lane, H. Clifford
Catalfamo, Marta
TI Chronic Exposure to Type-I IFN under Lymphopenic Conditions Alters CD4 T
Cell Homeostasis
SO PLOS PATHOGENS
LA English
DT Article
ID HEMATOPOIETIC STEM-CELLS; HIV-INFECTED PATIENTS; IMMUNE ACTIVATION;
INTERFERON-ALPHA; DENDRITIC CELLS; POTENTIAL ROLE; SIV INFECTION; HUMAN
NAIVE; IL-7; PROLIFERATION
AB HIV infection and the associated chronic immune activation alter T cell homeostasis leading to CD4 T cell depletion and CD8 T cell expansion. The mechanisms behind these outcomes are not totally defined and only partially explained by the direct cytopathic effect of the virus. In this manuscript, we addressed the impact of lymphopenia and chronic exposure to IFN-alpha on T cell homeostasis. In a lymphopenic murine model, this interaction led to decreased CD4 counts and CD8 T cell expansion in association with an increase in the Signal Transducer and Activator of Transcription 1 (STAT1) levels resulting in enhanced CD4 T cell responsiveness to IFN-alpha. Thus, in the setting of HIV infection, chronic stimulation of this pathway could be detrimental for CD4 T cell homeostasis.
C1 [Le Saout, Cecile; Hasley, Rebecca B.; Imamichi, Hiromi; Tcheung, Lueng; Smith, Mindy; Sneller, Michael C.; Lane, H. Clifford; Catalfamo, Marta] NIAID, CMRS, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Hu, Zonghui] NIAID, Biostat Res Branch, DCR, NIH, Bethesda, MD 20892 USA.
[Luckey, Megan A.; Park, Jung-Hyun] NCI, Expt Immunol Branch, CCR, NIH, Bethesda, MD 20892 USA.
[Durum, Scott K.] NCI, Immunoregulat Lab, CCR, NIH, Frederick, MD 21701 USA.
[Rupert, Adam W.] Leidos Biomed Res Inc, AIDS Monitoring Labs, Frederick, MD USA.
RP Le Saout, C (reprint author), NIAID, CMRS, Immunoregulat Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM catalfam@mail.nih.gov
RI Park, Jung Hyun /B-5712-2015; Davis, Megan/F-5339-2015
OI Park, Jung Hyun /0000-0002-9547-9055;
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
Contract No. HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 57
TC 3
Z9 3
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD MAR
PY 2014
VL 10
IS 3
AR e1003976
DI 10.1371/journal.ppat.1003976
PG 15
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA AJ2FF
UT WOS:000337470300026
PM 24603698
ER
PT J
AU Kuller, LH
Mackey, RH
Walitt, BT
Deane, KD
Holers, VM
Robinson, WH
Sokolove, J
Chang, YF
Liu, SM
Parks, CG
Wright, NC
Moreland, LW
AF Kuller, Lewis H.
Mackey, Rachel H.
Walitt, Brian T.
Deane, Kevin D.
Holers, V. Michael
Robinson, William H.
Sokolove, Jeremy
Chang, Yuefang
Liu, Simin
Parks, Christine G.
Wright, Nicole C.
Moreland, Larry W.
TI Determinants of Mortality Among Postmenopausal Women in the Women's
Health Initiative Who Report Rheumatoid Arthritis
SO ARTHRITIS & RHEUMATOLOGY
LA English
DT Article
ID CYCLIC CITRULLINATED PEPTIDE; PULMONARY-FIBROSIS; REVISED CRITERIA;
EXCESS MORTALITY; PREDICTIVE-VALUE; DISEASE; RISK; ASSOCIATION;
POPULATION; ANTIBODIES
AB Objective. Rheumatoid arthritis (RA) patients have an increased risk of cardiovascular disease (CVD) and mortality. We measured anti-cyclic citrullinated peptide (anti-CCP) antibody levels and determined use of disease-modifying antirheumatic drugs (DMARDs) among women in the Women's Health Initiative (WHI). Using these data, we undertook this study to assess total mortality over 10 years of followup among white, black, or Hispanic women with self-reported RA in the WHI.
Methods. Using stored baseline serum, we measured anti-CCP, rheumatoid factor (RF), and antinuclear antibodies (ANAs) in 9,988 women who reported having RA. Based on a previous chart review study, probable RA was defined as either self-reported RA and anti-CCP positivity, or anti-CCP negativity and DMARD use. Cox proportional hazards regression was used to model the relationship of self-reported RA, DMARD exposure, and anti-CCP positivity to total mortality, using followup data through April 2009.
Results. At baseline, the mean age was 62.8 years; 24.5% of subjects were black and 10% were Hispanic. Prevalence of anti-CCP positivity was 8.1% (n = 812), and 217 women were anti-CCP negative but had reported use of DMARDs; therefore, 1,029 women (of 9,988) were classified as having probable RA, and 8,958 were classified as unlikely to have RA (with data on DMARD use missing for 1 subject). Age-adjusted mortality rates were similar to 2-fold higher for anti-CCP-positive women, with 20.2 deaths per 1,000 person-years, as compared to 11.4 deaths per 1,000 person-years among anti-CCP-negative women with self-reported RA who never used DMARDs. Among women who did not report any arthritis at baseline, we found 8.3 deaths per 1,000 person-years. The increased risk among anti-CCP-positive women with RA was not explained by age, RF positivity, ANA positivity, or DMARD use.
Conclusion. Anti-CCP-positive RA was associated with substantial excess mortality among postmenopausal women in the WHI. This result was not explained by the risk factors we measured.
C1 [Kuller, Lewis H.; Mackey, Rachel H.; Chang, Yuefang; Moreland, Larry W.] Univ Pittsburgh, Pittsburgh, PA 15261 USA.
[Walitt, Brian T.] Washington Hosp Ctr, Washington, DC 20010 USA.
[Deane, Kevin D.; Holers, V. Michael] Univ Colorado, Denver, CO 80202 USA.
[Robinson, William H.; Sokolove, Jeremy] Stanford Univ, Stanford, CA 94305 USA.
[Liu, Simin] Brown Univ, Providence, RI 02912 USA.
[Parks, Christine G.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
[Wright, Nicole C.] Univ Alabama Birmingham, Birmingham, AL 35205 USA.
RP Kuller, LH (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, 130 North Bellefield Ave,Room 550, Pittsburgh, PA 15261 USA.
EM kullerl@edc.pitt.edu
RI Liu, Simin/I-3689-2014;
OI Liu, Simin/0000-0003-2098-3844; Mackey, Rachel/0000-0001-6088-2664;
Parks, Christine/0000-0002-5734-3456
FU NIH (National Heart, Lung, and Blood Institute [NHLBI]) [BAA-WH-09-01,
HHSN268200960006C]; NIH (NHLBI) [N01-WH-22110, N01-WH-24152,
N01-WH-32100-2, N01-WH-32105-6, N01-WH-32108-9, N01-WH-32111-13,
N01-WH-32115, N01-WH-32118-32119, N01-WH-32122, N01-WH-42107-26,
N01-WH-42129-32, N01-WH-44221]
FX Supported by the NIH (National Heart, Lung, and Blood Institute [NHLBI]
BAA-WH-09-01 contract HHSN268200960006C). The Women's Health Initiative
program is funded by the NIH (NHLBI contracts N01-WH-22110,
N01-WH-24152, N01-WH-32100-2, N01-WH-32105-6, N01-WH-32108-9,
N01-WH-32111-13, N01-WH-32115, N01-WH-32118-32119, N01-WH-32122,
N01-WH-42107-26, N01-WH-42129-32, and N01-WH-44221).
NR 53
TC 8
Z9 9
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2326-5191
EI 2326-5205
J9 ARTHRITIS RHEUMATOL
JI Arthritis Rheumatol.
PD MAR
PY 2014
VL 66
IS 3
BP 497
EP 507
DI 10.1002/art.38268
PG 11
WC Rheumatology
SC Rheumatology
GA AJ0QD
UT WOS:000337359400004
PM 24574208
ER
PT J
AU Aggarwal, R
Bandos, A
Reed, AM
Ascherman, DP
Barohn, RJ
Feldman, BM
Miller, FW
Rider, LG
Harris-Love, MO
Levesque, MC
Oddis, CV
AF Aggarwal, Rohit
Bandos, Andriy
Reed, Ann M.
Ascherman, Dana P.
Barohn, Richard J.
Feldman, Brian M.
Miller, Frederick W.
Rider, Lisa G.
Harris-Love, Michael O.
Levesque, Marc C.
Oddis, Chester V.
CA Rim Study Grp
TI Predictors of Clinical Improvement in Rituximab-Treated Refractory Adult
and Juvenile Dermatomyositis and Adult Polymyositis
SO ARTHRITIS & RHEUMATOLOGY
LA English
DT Article
ID IDIOPATHIC INFLAMMATORY MYOPATHIES; TRANSFER-RNA-SYNTHETASE;
MYOSITIS-SPECIFIC AUTOANTIBODIES; PROGNOSTIC-FACTORS; JAPANESE PATIENTS;
DISEASE-ACTIVITY; TERM; SURVIVAL; ANTIBODY; TRIAL
AB Objective. To identify the clinical and laboratory predictors of clinical improvement in a cohort of myositis patients treated with rituximab.
Methods. We analyzed data for 195 patients with myositis (75 with adult polymyositis [PM], 72 with adult dermatomyositis [DM], and 48 with juvenile DM) in the Rituximab in Myositis trial. Clinical improvement was defined as 20% improvement in at least 3 of the following 6 core set measures of disease activity: physician's and patient's/parent's global assessment of disease activity, manual muscle testing, physical function, muscle enzymes, and extramuscular disease activity. We analyzed the association of the following baseline variables with improvement: myositis clinical subgroup, demographics, myositis damage, clinical and laboratory parameters, core set measures, rituximab treatment, and myositis autoantibodies (antisynthetase, anti-Mi-2, anti-signal recognition particle, anti-transcription intermediary factor 1 gamma [TIF-1 gamma], anti-MJ, other autoantibodies, and no autoantibodies). All measures were univariately assessed for association with improvement using time-to-event analyses. A multivariable time-dependent proportional hazards model was used to evaluate the association of individual predictive factors with improvement.
Results. In the final multivariable model, the presence of an antisynthetase, primarily anti-Jo-1 (hazard ratio [HR] 3.08, P < 0.01), anti-Mi-2 (HR 2.5, P < 0.01), or other autoantibody (HR 1.4, P = 0.14) predicted a shorter time to improvement compared to the absence of autoantibodies. A lower physician's global assessment of damage (HR 2.32, P = 0.02) and juvenile DM (versus adult myositis) (HR 2.45, P = 0.01) also predicted improvement. Unlike autoantibody status, the predictive effect of physician's global assessment of damage and juvenile DM diminished by week 20. Rituximab treatment did not affect these associations.
Conclusion. Our findings indicate that the presence of antisynthetase and anti-Mi-2 autoantibodies, juvenile DM subset, and lower disease damage strongly predict clinical improvement in patients with refractory myositis.
C1 [Aggarwal, Rohit; Bandos, Andriy; Levesque, Marc C.; Oddis, Chester V.] Univ Pittsburgh, Pittsburgh, PA 15261 USA.
[Reed, Ann M.] Mayo Clin, Rochester, MN USA.
[Ascherman, Dana P.] Univ Miami, Miami, FL USA.
[Barohn, Richard J.] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA.
[Feldman, Brian M.] Hosp Sick Children, Toronto, ON, Canada.
[Feldman, Brian M.] Univ Toronto, Toronto, ON, Canada.
[Miller, Frederick W.; Rider, Lisa G.] Natl Inst Environm Hlth Sci, NIH, Bethesda, MD USA.
[Harris-Love, Michael O.] Washington DC VA Med Ctr, Washington, DC USA.
RP Aggarwal, R (reprint author), Univ Pittsburgh, BST S705A,3500 Terrace St, Pittsburgh, PA 15261 USA.
EM aggarwalr@upmc.edu
RI Harris-Love, Michael/J-1359-2014;
OI Harris-Love, Michael/0000-0002-1842-3269; Rider,
Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593
FU NIH (National Institute of Arthritis and Musculoskeletal and Skin
Diseases) [N01-AR-4-2273]; NIH (National Institute of Environmental
Health Sciences) [M01-RR-023940/UL1-RR-033179]; Genentech Inc.;
Questcor; aTyr Pharma; Genentech; Novartis; Grifols
FX Supported by the NIH (National Institute of Arthritis and
Musculoskeletal and Skin Diseases contract N01-AR-4-2273), the
Intramural Program of the NIH (National Institute of Environmental
Health Sciences), a General Clinical Research Center/Clinical and
Translational Science Award (M01-RR-023940/UL1-RR-033179) to the
University of Kansas Medical Center, and by Genentech Inc.; Dr. Aggarwal
has received consulting fees and/or honoraria from Questcor and aTyr
Pharma for service on the Advisory Boards of the companies (less than
$10,000 each). Dr. Reed has received consulting fees and/or honoraria
from Genentech for service on the Genentech Advisory Board (less than
$10,000). Dr. Barohn has received consulting fees from Novartis (more
than $10,000) and speaking fees from Grifols (more than $10,000). Dr.
Feldman has received consulting fees, speaking fees, and/or honoraria
from Novartis (less than $10,000). Dr. Levesque has received consulting
fees, speaking fees, and/or honoraria from Genentech (less than $10,000)
and has received research support from Genentech. Dr. Oddis has received
consulting fees from Questcor (less than $10,000) and has served as an
expert witness concerning appropriateness of rituximab therapy in a
patient with myositis.
NR 42
TC 44
Z9 45
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2326-5191
EI 2326-5205
J9 ARTHRITIS RHEUMATOL
JI Arthritis Rheumatol.
PD MAR
PY 2014
VL 66
IS 3
BP 740
EP 749
DI 10.1002/art.38270
PG 10
WC Rheumatology
SC Rheumatology
GA AJ0QD
UT WOS:000337359400031
PM 24574235
ER
PT J
AU Blanchet, EM
Millo, C
Martucci, V
Maass-Moreno, R
Bluemke, DA
Pacak, K
AF Blanchet, Elise M.
Millo, Corina
Martucci, Victoria
Maass-Moreno, Roberto
Bluemke, David A.
Pacak, Karel
TI Integrated Whole-Body PET/MRI With F-18-FDG, F-18-FDOPA, and F-18-FDA in
Paragangliomas in Comparison With PET/CT NIH First Clinical Experience
With a Single-Injection, Dual-Modality Imaging Protocol
SO CLINICAL NUCLEAR MEDICINE
LA English
DT Article
DE pheochromocytoma; paraganglioma; PET/MRI; F-18-FDG; F-18-fluorodopamine;
F-18-fluorodihydroxyphenylalanine
ID EMISSION TOMOGRAPHY/COMPUTED TOMOGRAPHY; ATTENUATION CORRECTION;
FUNCTIONAL-CHARACTERIZATION; NEUROENDOCRINE TUMORS; INITIAL-EXPERIENCE;
PHEOCHROMOCYTOMA; MR; CT; PERFORMANCE; SCANNER
AB Purpose: Paragangliomas (PGLs) are tumors that can metastasize and recur; therefore, lifelong imaging follow-up is required. Hybrid PET/CT is an essential tool to image PGLs. Novel hybrid PET/MRI scanners are currently being studied in clinical oncology. We studied the feasibility of simultaneous whole-body PET/MRI to evaluate patients with PGLs.
Methods: Fifty-three PGLs or PGL-related lesions from 8 patients were evaluated. All patients underwent a single-injection, dual-modality imaging protocol consisting of a PET/CT and a subsequent PET/MRI scan. Four patients were evaluated with F-18-FDG, 2 with F-18-fluorodihydroxyphenylalanine, and 2 with F-18-fluorodopamine. PET/MRI data were acquired using a hybrid whole-body 3-tesla integrated PET/MRI scanner. PET and MRI data (Dixon sequence for attenuation correction and T2-weighted sequences for anatomic allocation) were acquired simultaneously. Imaging workflow and imaging times were documented. PET/MRI and PET/CT data were visually assessed (blindly) in regards to image quality, lesion detection, and anatomic allocation and delineation of the PET findings.
Results: With hybrid PET/MRI, we obtained high-quality images in an acceptable acquisition time (median, 31 minutes; range, 25-40 minutes) with good patient compliance. A total of 53 lesions, located in the head and neck area (6 lesions), mediastinum (2 lesions), abdomen and pelvis (13 lesions), lungs (2 lesions), liver (4 lesions), and bones (26 lesions), were evaluated. Fifty-one lesions were detected with PET/MRI and confirmed by PET/CT. Two bone lesions (L4 body, 8 mm, and sacrum, 6 mm) were not detectable on an F-18-FDA scan PET/MRI, likely because F-18-FDA was washed out between PET/CT and PET/MRI acquisitions. Coregistered MRI tended to be superior to coregistered CT for head and neck, abdomen, pelvis, and liver lesions for anatomic allocation and delineation.
Conclusions: Clinical PGL evaluation with hybrid PET/MRI is feasible with high-quality image and can be obtained in a reasonable time. It could be particularly beneficial for the pediatric population and for precise lesion definition in the head and neck, abdomen, pelvis, and liver.
C1 [Blanchet, Elise M.; Martucci, Victoria; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Bethesda, MD USA.
[Millo, Corina] NIH, Dept PET, Warren Magnuson Clin Ctr, Bethesda, MD 20892 USA.
[Maass-Moreno, Roberto] NIH, Dept Nucl Med, Warren Magnuson Clin Ctr, Bethesda, MD USA.
[Bluemke, David A.] NIH, Dept Radiol & Imaging Sci, Warren Magnuson Clin Ctr, Bethesda, MD 20892 USA.
RP Blanchet, EM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bldg 10,CRC 1 E,Rm 1-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA.
EM elise.blanchet@gmail.com
OI Bluemke, David/0000-0002-8323-8086
NR 41
TC 4
Z9 5
U1 1
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0363-9762
EI 1536-0229
J9 CLIN NUCL MED
JI Clin. Nucl. Med.
PD MAR
PY 2014
VL 39
IS 3
BP 243
EP 250
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AI9YP
UT WOS:000337304400018
PM 24152658
ER
PT J
AU Likhtarov, I
Kovgan, L
Masiuk, S
Talerko, M
Chepurny, M
Ivanova, O
Gerasymenko, V
Boyko, Z
Voilleque, P
Drozdovitch, V
Bouville, A
AF Likhtarov, Ilya
Kovgan, Lina
Masiuk, Sergii
Talerko, Mykola
Chepurny, Mykola
Ivanova, Olga
Gerasymenko, Valentina
Boyko, Zulfira
Voilleque, Paul
Drozdovitch, Vladimir
Bouville, Andre
TI THYROID CANCER STUDY AMONG UKRAINIAN CHILDREN EXPOSED TO RADIATION AFTER
THE CHORNOBYL ACCIDENT: IMPROVED ESTIMATES OF THE THYROID DOSES TO THE
COHORT MEMBERS
SO HEALTH PHYSICS
LA English
DT Article
DE I-131; Chernobyl; dose assessment; thyroid
ID RADIOACTIVE CONTAMINATION; RECONSTRUCTION; I-131; POPULATION;
UNCERTAINTIES; MILK
AB In collaboration with the Ukrainian Research Center for Radiation Medicine, the U. S. National Cancer Institute initiated a cohort study of children and adolescents exposed to Chornobyl fallout in Ukraine to better understand the long-term health effects of exposure to radioactive iodines. All 13,204 cohort members were subjected to at least one direct thyroid measurement between 30 April and 30 June 1986 and resided at the time of the accident in the northern parts of Kyiv, Zhytomyr, or Chernihiv Oblasts, which were the most contaminated territories of Ukraine as a result of radioactive fallout from the Chornobyl accident. Thyroid doses for the cohort members, which had been estimated following the first round of interviews, were re-evaluated following the second round of interviews. The revised thyroid doses range from 0.35 mGy to 42 Gy, with 95% of the doses between 1 mGy and 4.2 Gy, an arithmetic mean of 0.65 Gy, and a geometric mean of 0.19 Gy. These means are 70% of the previous estimates, mainly because of the use of country-specific thyroid masses. Many of the individual thyroid dose estimates show substantial differences because of the use of an improved questionnaire for the second round of interviews. Limitations of the current set of thyroid dose estimates are discussed. For the epidemiologic study, the most notable improvement is a revised assessment of the uncertainties, as shared and unshared uncertainties in the parameter values were considered in the calculation of the 1,000 stochastic estimates of thyroid dose for each cohort member. This procedure makes it possible to perform a more realistic risk analysis.
C1 [Likhtarov, Ilya; Kovgan, Lina; Masiuk, Sergii; Chepurny, Mykola; Ivanova, Olga; Gerasymenko, Valentina; Boyko, Zulfira] Natl Acad Med Sci Ukraine, Natl Res Ctr Radiat Med, State Inst, UA-04050 Kiev, Ukraine.
[Talerko, Mykola] Natl Acad Sci Ukraine, Inst Safety Problems Nucl Power Plants, UA-03028 Kiev, Ukraine.
[Voilleque, Paul] MJP Risk Assessment Inc, Denver, CO 80220 USA.
[Drozdovitch, Vladimir] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
[Bouville, Andre] US Natl Canc Inst, Bethesda, MD USA.
RP Drozdovitch, V (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 9609 Med Ctr Dr,7E548, Bethesda, MD 20892 USA.
EM drozdovv@mail.nih.gov
FU U.S. National Cancer Institute, National Institutes of Health
FX The authors are grateful to all of the subjects who participated in the
study. Special thanks are to the staff of V.P. Komisarenko Institute of
Endocrinology and Metabolism of the National Academy of Medical Sciences
of Ukraine (Kyiv, Ukraine), who conducted personal interviews. The
authors thank Cindy Clark, NIH Library Writing Center, for manuscript
editing assistance. The research was supported by the Intramural
Research Program of the U.S. National Cancer Institute, National
Institutes of Health, within the framework of the Ukraine-U.S. Study of
Thyroid Cancer and Other Diseases Following the Chornobyl Accident.
NR 58
TC 10
Z9 10
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0017-9078
EI 1538-5159
J9 HEALTH PHYS
JI Health Phys.
PD MAR
PY 2014
VL 106
IS 3
BP 370
EP 396
DI 10.1097/HP.0b013e31829f3096
PG 27
WC Environmental Sciences; Public, Environmental & Occupational Health;
Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical
Imaging
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Nuclear Science & Technology; Radiology, Nuclear Medicine &
Medical Imaging
GA AJ2TC
UT WOS:000337514800004
PM 25208014
ER
PT J
AU Bashirova, AA
Martin-Gayo, E
Jones, DC
Qi, Y
Apps, R
Gao, XJ
Burke, PS
Taylor, CJ
Rogich, J
Wolinsky, S
Bream, JH
Duggal, P
Hussain, S
Martinson, J
Weintrob, A
Kirk, GD
Fellay, J
Buchbinder, SP
Goedert, JJ
Deeks, SG
Pereyra, F
Trowsdale, J
Lichterfeld, M
Telenti, A
Walker, BD
Allen, RL
Carrington, M
Yu, XG
AF Bashirova, Arman A.
Martin-Gayo, Enrique
Jones, Des C.
Qi, Ying
Apps, Richard
Gao, Xiaojiang
Burke, Patrick S.
Taylor, Craig J.
Rogich, Jerome
Wolinsky, Steven
Bream, Jay H.
Duggal, Priya
Hussain, Shehnaz
Martinson, Jeremy
Weintrob, Amy
Kirk, Gregory D.
Fellay, Jacques
Buchbinder, Susan P.
Goedert, James J.
Deeks, Steven G.
Pereyra, Florencia
Trowsdale, John
Lichterfeld, Mathias
Telenti, Amalio
Walker, Bruce D.
Allen, Rachel L.
Carrington, Mary
Yu, Xu G.
TI LILRB2 Interaction with HLA Class I Correlates with Control of HIV-1
Infection
SO PLOS GENETICS
LA English
DT Article
ID MHC CLASS-I; INHIBITORY RECEPTOR; DENDRITIC CELLS; MYELOMONOCYTIC CELLS;
HOST CONTROL; MOLECULES; AIDS; COMPLEX; BINDING; ILT4
AB Natural progression of HIV-1 infection depends on genetic variation in the human major histocompatibility complex (MHC) class I locus, and the CD8(+) T cell response is thought to be a primary mechanism of this effect. However, polymorphism within the MHC may also alter innate immune activity against human immunodeficiency virus type 1 (HIV-1) by changing interactions of human leukocyte antigen (HLA) class I molecules with leukocyte immunoglobulin-like receptors (LILR), a group of immunoregulatory receptors mainly expressed on myelomonocytic cells including dendritic cells (DCs). We used previously characterized HLA allotype-specific binding capacities of LILRB1 and LILRB2 as well as data from a large cohort of HIV-1-infected individuals (N = 5126) to test whether LILR-HLA class I interactions influence viral load in HIV-1 infection. Our analyses in persons of European descent, the largest ethnic group examined, show that the effect of HLA-B alleles on HIV-1 control correlates with the binding strength between corresponding HLA-B allotypes and LILRB2 (p = 10(-2)). Moreover, overall binding strength of LILRB2 to classical HLA class I allotypes, defined by the HLA-A/B/C genotypes in each patient, positively associates with viral replication in the absence of therapy in patients of both European (p = 10(-11)-10(-9)) and African (p = 10(-5)-10(-3)) descent. This effect appears to be driven by variations in LILRB2 binding affinities to HLA-B and is independent of individual class I allelic effects that are not related to the LILRB2 function. Correspondingly, in vitro experiments suggest that strong LILRB2-HLA binding negatively affects antigen-presenting properties of DCs. Thus, we propose an impact of LILRB2 on HIV-1 disease outcomes through altered regulation of DCs by LILRB2-HLA engagement.
C1 [Bashirova, Arman A.; Qi, Ying; Apps, Richard; Gao, Xiaojiang; Carrington, Mary] Leidos Biomed Res Inc, Canc & Inflammat Program, Expt Immunol Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Bashirova, Arman A.; Martin-Gayo, Enrique; Burke, Patrick S.; Rogich, Jerome; Pereyra, Florencia; Walker, Bruce D.; Carrington, Mary; Yu, Xu G.] Ragon Inst MGH MIT & Harvard, Boston, MA USA.
[Jones, Des C.; Trowsdale, John] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England.
[Taylor, Craig J.] Addenbrookes Hosp, Tissue Typing Labs, Cambridge, England.
[Wolinsky, Steven] Northwestern Univ, Sch Med, Chicago, IL USA.
[Bream, Jay H.; Duggal, Priya] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA.
[Hussain, Shehnaz] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Los Angeles, CA USA.
[Martinson, Jeremy] Univ Pittsburgh, Pittsburgh, PA USA.
[Weintrob, Amy] USU Infect Dis Clin Res Program, Bethesda, MD USA.
[Kirk, Gregory D.] Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA.
[Fellay, Jacques] Ecole Polytech Fed Lausanne, Sch Life Sci, Lausanne, Switzerland.
[Buchbinder, Susan P.] San Francisco Dept Publ Hlth, San Francisco, CA USA.
[Goedert, James J.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Deeks, Steven G.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA.
[Pereyra, Florencia] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA.
[Lichterfeld, Mathias] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Telenti, Amalio] Univ Lausanne Hosp, Inst Microbiol, Lausanne, Switzerland.
[Telenti, Amalio] Univ Lausanne, Lausanne, Switzerland.
[Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA.
[Allen, Rachel L.] Univ London, St Georges Med Sch, London, England.
RP Bashirova, AA (reprint author), Leidos Biomed Res Inc, Canc & Inflammat Program, Expt Immunol Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
EM xyu@partners.org
RI SHCS, int. coll. A/G-4083-2011; Fellay, Jacques/A-6681-2009; SHCS,
all/G-4072-2011;
OI Fellay, Jacques/0000-0002-8240-939X; Martinson,
Jeremy/0000-0003-4673-7238; Wolinsky, Steven/0000-0002-9625-6697
FU Frederick National Laboratory for Cancer Research [HHSN261200800001E];
NIH, Frederick National Lab, Center for Cancer Research; NIAID [R01
AI087145, K24 AI069994, R24 AI067039]; UCSF/Gladstone CFAR [P30
AI027763]; UCSF CTSI [UL1 RR024131]; Center for AIDS Prevention Studies
[P30 MH62246]; Bill and Melinda Gates Foundation; AIDS Healthcare
Foundation; Harvard University Center for AIDS Research (CFAR), an NIH
[P30 AI060354]; NIAID, NIH; NCI, NIH; NICHD, NIH; NHLBI, NIH; NIDA, NIH;
NIMH, NIH; NIA, NIH; FIC, NIH; OAR, NIH; Swiss National Science
Foundation; NIH/NIAID [R01 AI078799, R56 AI098484, R01 AI087452, R01
AI089339]; MRC; Wellcome Trust; AICR; NIHR Cambridge BRC; National
Institute of Allergy and Infectious Diseases; National Cancer Institute;
National Heart, Lung, and Blood Institute [U01-AI-35042, UL1-RR025005,
U01-AI-35043, U01-AI-35039, U01-AI-35040, U01-AI-35041]
FX This project has been funded in whole or in part with federal funds from
the Frederick National Laboratory for Cancer Research, under Contract
No. HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government.
This Research was supported in part by the Intramural Research Program
of the NIH, Frederick National Lab, Center for Cancer Research. The
SCOPE cohort was supported in part by the NIAID (R01 AI087145, K24
AI069994, R24 AI067039), UCSF/Gladstone CFAR (P30 AI027763), the UCSF
CTSI (UL1 RR024131), and the Center for AIDS Prevention Studies (P30
MH62246). The International HIV Controllers Study (IHCS), was funded by
the Bill and Melinda Gates Foundation, the AIDS Healthcare Foundation
and the Harvard University Center for AIDS Research (CFAR), an NIH
funded program(P30 AI060354), which is supported by the following NIH
Co-Funding and Participating Institutes and Centers: NIAID, NCI, NICHD,
NHLBI, NIDA, NIMH, NIA, FIC and OAR. Members of the International HIV
Controllers Study can be found at www.hivcontrollers.org. The Swiss HIV
Cohort study (www.shcs.ch) is funded by the Swiss National Science
Foundation. XGY was supported by NIH/NIAID R01 AI078799, R56 AI098484,
R01 AI087452 and R01 AI089339. JT and DCJ were supported by the MRC,
Wellcome Trust and AICR, with partial funding from the NIHR Cambridge
BRC. We thank Randy Johnson and George Nelson for helpful discussions.
We are grateful to the USU Infectious Disease Clinical Research Program
HIV Working Group for collecting and providing clinical data. The MACS
clinical data used in this manuscript were collected at: The Johns
Hopkins Bloomberg School of Public Health (Joseph Margolick); Howard
Brown Health Center and Northwestern University Medical School (John
Phair, Steven Wolinsky); University of California, Los Angeles (Roger
Detels, Oto Martinez-Maza); University of Pittsburgh (Charles Rinaldo);
and Data Analysis Center (Lisa Jacobson). The MACS is funded by the
National Institute of Allergy and Infectious Diseases, with additional
supplemental funding from the National Cancer Institute; and the
National Heart, Lung, and Blood Institute: U01-AI-35042, UL1-RR025005
(GCRC), U01-AI-35043, U01-AI-35039, U01-AI-35040, and U01-AI-35041. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 40
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PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7390
EI 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD MAR
PY 2014
VL 10
IS 3
AR e1004196
DI 10.1371/journal.pgen.1004196
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA AI8FM
UT WOS:000337144700026
PM 24603468
ER
PT J
AU Bentley, AR
Chen, GJ
Shriner, D
Doumatey, AP
Zhou, J
Huang, HX
Mullikin, JC
Blakesley, RW
Hansen, NF
Bouffard, GG
Cherukuri, PF
Maskeri, B
Young, AC
Adeyemo, A
Rotimi, CN
AF Bentley, Amy R.
Chen, Guanjie
Shriner, Daniel
Doumatey, Ayo P.
Zhou, Jie
Huang, Hanxia
Mullikin, James C.
Blakesley, Robert W.
Hansen, Nancy F.
Bouffard, Gerard G.
Cherukuri, Praveen F.
Maskeri, Baishali
Young, Alice C.
Adeyemo, Adebowale
Rotimi, Charles N.
TI Gene-Based Sequencing Identifies Lipid-Influencing Variants with
Ethnicity-Specific Effects in African Americans
SO PLOS GENETICS
LA English
DT Article
ID DENSITY-LIPOPROTEIN CHOLESTEROL; METABOLIC SYNDROME; HDL-CHOLESTEROL;
BLOOD-LIPIDS; ADMIXED POPULATIONS; LINKAGE ANALYSIS; CANDIDATE GENES;
ASSOCIATION; LIPASE; POLYMORPHISMS
AB Although a considerable proportion of serum lipids loci identified in European ancestry individuals (EA) replicate in African Americans (AA), interethnic differences in the distribution of serum lipids suggest that some genetic determinants differ by ethnicity. We conducted a comprehensive evaluation of five lipid candidate genes to identify variants with ethnicity-specific effects. We sequenced ABCA1, LCAT, LPL, PON1, and SERPINE1 in 48 AA individuals with extreme serum lipid concentrations (high HDLC/low TG or low HDLC/high TG). Identified variants were genotyped in the full population-based sample of AA (n = 1694) and tested for an association with serum lipids. rs328 (LPL) and correlated variants were associated with higher HDLC and lower TG. Interestingly, a stronger effect was observed on a "European'' vs. "African'' genetic background at this locus. To investigate this effect, we evaluated the region among West Africans (WA). For TG, the effect size among WA was the same in AA with only African local ancestry (2-3% lower TG), while the larger association among AA with local European ancestry matched previous reports in EA (10%). For HDLC, there was no association with rs328 in AA with only African local ancestry or in WA, while the association among AA with European local ancestry was much greater than what has been observed for EA (15 vs. similar to 5 mg/dl), suggesting an interaction with an environmental or genetic factor that differs by ethnicity. Beyond this ancestry effect, the importance of African ancestry-focused, sequence-based work was also highlighted by serum lipid associations of variants that were in higher frequency (or present only) among those of African ancestry. By beginning our study with the sequence variation present in AA individuals, investigating local ancestry effects, and seeking replication in WA, we were able to comprehensively evaluate the role of a set of candidate genes in serum lipids in AA.
C1 [Bentley, Amy R.; Chen, Guanjie; Shriner, Daniel; Doumatey, Ayo P.; Zhou, Jie; Huang, Hanxia; Adeyemo, Adebowale; Rotimi, Charles N.] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA.
[Mullikin, James C.; Blakesley, Robert W.; Bouffard, Gerard G.; Maskeri, Baishali; Young, Alice C.] NHGRI, NIH, Intramural Sequencing Ctr, Bethesda, MD 20892 USA.
[Hansen, Nancy F.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
[Cherukuri, Praveen F.] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Bentley, AR (reprint author), NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA.
EM amy.bentley@mail.nih.gov; rotimic@mail.nih.gov
OI Adeyemo, Adebowale/0000-0002-3105-3231
FU NIGMS/MBRS/SCORE Program [S06GM008016-320107, S06GM008016-380111];
National Center for Research Resources, a component of the NIH
[2M01RR010284]; National Human Genome Research Institute in the Center
for Research in Genomics and Global Health [CRGGH-Z01HG200362]; National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Center
for Information Technology; Office of the Director at the NIH; National
Institute on Minority Health and Health Disparities; NIDDK; NHGRI
FX The study was supported by grants S06GM008016-320107 to CNR and
S06GM008016-380111 to AA, both from the NIGMS/MBRS/SCORE Program.
Participant enrollment was carried out at the Howard University General
Clinical Research Center, which is supported by grant 2M01RR010284 from
the National Center for Research Resources, a component of the NIH. This
research was supported in part by the Intramural Research Program of the
National Human Genome Research Institute in the Center for Research in
Genomics and Global Health (CRGGH-Z01HG200362). CRGGH is also supported
by National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK), Center for Information Technology, and the Office of the
Director at the NIH. Support for the Africa America Diabetes Mellitus
(AADM) study is provided by the National Institute on Minority Health
and Health Disparities, NIDDK, and NHGRI. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 60
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PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7390
EI 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD MAR
PY 2014
VL 10
IS 3
AR e1004190
DI 10.1371/journal.pgen.1004190
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA AI8FM
UT WOS:000337144700022
PM 24603370
ER
PT J
AU Haeusser, DP
Hoashi, M
Weaver, A
Brown, N
Pan, J
Sawitzke, JA
Thomason, LC
Court, DL
Margolin, W
AF Haeusser, Daniel P.
Hoashi, Marina
Weaver, Anna
Brown, Nathan
Pan, James
Sawitzke, James A.
Thomason, Lynn C.
Court, Donald L.
Margolin, William
TI The Kil Peptide of Bacteriophage lambda Blocks Escherichia coli
Cytokinesis via ZipA-Dependent Inhibition of FtsZ Assembly
SO PLOS GENETICS
LA English
DT Article
ID BACTERIAL-CELL-DIVISION; CYTOSKELETAL PROTEIN FTSZ; HIGH-LEVEL
EXPRESSION; Z-RING; BACILLUS-SUBTILIS; GENE-PRODUCT; IMAGE-ANALYSIS;
CROSS-LINKING; MECHANISM; SULA
AB Assembly of the essential, tubulin-like FtsZ protein into a ring-shaped structure at the nascent division site determines the timing and position of cytokinesis in most bacteria and serves as a scaffold for recruitment of the cell division machinery. Here we report that expression of bacteriophage lambda kil, either from a resident phage or from a plasmid, induces filamentation of Escherichia coli cells by rapid inhibition of FtsZ ring formation. Mutant alleles of ftsZ resistant to the Kil protein map to the FtsZ polymer subunit interface, stabilize FtsZ ring assembly, and confer increased resistance to endogenous FtsZ inhibitors, consistent with Kil inhibiting FtsZ assembly. Cells with the normally essential cell division gene zipA deleted (in a modified background) display normal FtsZ rings after kil expression, suggesting that ZipA is required for Kil-mediated inhibition of FtsZ rings in vivo. In support of this model, point mutations in the C-terminal FtsZ-interaction domain of ZipA abrogate Kil activity without discernibly altering FtsZ-ZipA interactions. An affinity-tagged-Kil derivative interacts with both FtsZ and ZipA, and inhibits sedimentation of FtsZ filament bundles in vitro. Together, these data inspire a model in which Kil interacts with FtsZ and ZipA in the cell to prevent FtsZ assembly into a coherent, division-competent ring structure. Phage growth assays show that kil(+) phage lyse similar to 30% later than kil mutant phage, suggesting that Kil delays lysis, perhaps via its interaction with FtsZ and ZipA.
C1 [Haeusser, Daniel P.; Margolin, William] Univ Texas Med Sch Houston, Dept Microbiol & Mol Genet, Houston, TX 77030 USA.
[Hoashi, Marina; Weaver, Anna; Brown, Nathan; Pan, James; Sawitzke, James A.; Court, Donald L.] NCI, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21701 USA.
[Thomason, Lynn C.] Leidos Biomed Inc, Frederick Natl Lab Canc Res, Gene Regulat & Chromosome Biol Lab, Frederick, MD USA.
RP Haeusser, DP (reprint author), Univ Texas Med Sch Houston, Dept Microbiol & Mol Genet, Houston, TX 77030 USA.
EM courtd@mail.nih.gov; William.Margolin@uth.tmc.edu
FU NIH, National Cancer Institute, Center for Cancer Research; National
Cancer Institute, National Institutes of Health [HHSN261200800001E];
NIGMS [R01-GM61074]
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 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 Health and Human Services, nor does mention of trade
names, commercial products, or organizations imply endorsement by the
U.S. Government. This work was also funded through NIGMS grant
R01-GM61074 to WM. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 99
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PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7390
EI 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD MAR
PY 2014
VL 10
IS 3
AR e1004217
DI 10.1371/journal.pgen.1004217
PG 25
WC Genetics & Heredity
SC Genetics & Heredity
GA AI8FM
UT WOS:000337144700042
PM 24651041
ER
PT J
AU Weinberg, CR
Shi, M
DeRoo, LA
Taylor, JA
Sandler, DP
Umbach, DM
AF Weinberg, Clarice R.
Shi, Min
DeRoo, Lisa A.
Taylor, Jack A.
Sandler, Dale P.
Umbach, David M.
TI Asymmetry in Family History Implicates Nonstandard Genetic Mechanisms:
Application to the Genetics of Breast Cancer
SO PLOS GENETICS
LA English
DT Article
ID CASE-PARENT-TRIAD; RISK; VARIANTS; COHORT
AB Genome-wide association studies typically target inherited autosomal variants, but less studied genetic mechanisms can play a role in complex disease. Sex-linked variants aside, three genetic phenomena can induce differential risk in maternal versus paternal lineages of affected individuals: 1. maternal effects, reflecting the maternal genome's influence on prenatal development; 2. mitochondrial variants, which are inherited maternally; 3. autosomal genes, whose effects depend on parent of origin. We algebraically show that small asymmetries in family histories of affected individuals may reflect much larger genetic risks acting via those mechanisms. We apply these ideas to a study of sisters of women with breast cancer. Among 5,091 distinct families of women reporting that exactly one grandmother had breast cancer, risk was skewed toward maternal grandmothers (p<0.0001), especially if the granddaughter was diagnosed between age 45 and 54. Maternal genetic effects, mitochondrial variants, or variant genes with parent-of-origin effects may influence risk of perimenopausal breast cancer.
C1 [Weinberg, Clarice R.; Shi, Min; Umbach, David M.] NIEHS, Biostat Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[DeRoo, Lisa A.; Taylor, Jack A.; Sandler, Dale P.] NIEHS, Epidemiol Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
RP Weinberg, CR (reprint author), NIEHS, Biostat Branch, NIH, DHHS, POB 12233, Res Triangle Pk, NC 27709 USA.
EM weinber2@niehs.nih.gov
OI taylor, jack/0000-0001-5303-6398; Sandler, Dale/0000-0002-6776-0018
FU NIH, National Institute of Environmental Health Sciences [Z01-ES040007,
Z01-ES45002]
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Environmental Health Sciences (Z01-ES040007;
Z01-ES45002). The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 24
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U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7390
EI 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD MAR
PY 2014
VL 10
IS 3
AR e1004174
DI 10.1371/journal.pgen.1004174
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA AI8FM
UT WOS:000337144700013
PM 24651610
ER
PT J
AU Williams, SR
Yang, Q
Chen, F
Liu, X
Keene, KL
Jacques, P
Chen, WM
Weinstein, G
Hsu, FC
Beiser, A
Wang, LW
Bookman, E
Doheny, KF
Wolf, PA
Zilka, M
Selhub, J
Nelson, S
Gogarten, SM
Worrall, BB
Seshadri, S
Sale, MM
AF Williams, Stephen R.
Yang, Qiong
Chen, Fang
Liu, Xuan
Keene, Keith L.
Jacques, Paul
Chen, Wei-Min
Weinstein, Galit
Hsu, Fang-Chi
Beiser, Alexa
Wang, Liewei
Bookman, Ebony
Doheny, Kimberly F.
Wolf, Philip A.
Zilka, Michelle
Selhub, Jacob
Nelson, Sarah
Gogarten, Stephanie M.
Worrall, Bradford B.
Seshadri, Sudha
Sale, Michele M.
CA Genomics Randomized Trials Network
Framingham Heart Study
TI Genome-Wide Meta-Analysis of Homocysteine and Methionine Metabolism
Identifies Five One Carbon Metabolism Loci and a Novel Association of
ALDH1L1 with Ischemic Stroke
SO PLOS GENETICS
LA English
DT Article
ID INDEPENDENT RISK-FACTOR; CYSTATHIONINE BETA-SYNTHASE; GLYCINE
N-METHYLTRANSFERASE; VASCULAR-DISEASE; PLASMA HOMOCYSTEINE; DNA
METHYLATION; GENETIC POLYMORPHISMS; VITAMIN INTERVENTION;
MOLECULAR-BASIS; POTENTIAL ROLE
AB Circulating homocysteine levels (tHcy), a product of the folate one carbon metabolism pathway (FOCM) through the demethylation of methionine, are heritable and are associated with an increased risk of common diseases such as stroke, cardiovascular disease (CVD), cancer and dementia. The FOCM is the sole source of de novo methyl group synthesis, impacting many biological and epigenetic pathways. However, the genetic determinants of elevated tHcy (hyperhomocysteinemia), dysregulation of methionine metabolism and the underlying biological processes remain unclear. We conducted independent genome-wide association studies and a meta-analysis of methionine metabolism, characterized by post-methionine load test tHcy, in 2,710 participants from the Framingham Heart Study (FHS) and 2,100 participants from the Vitamin Intervention for Stroke Prevention (VISP) clinical trial, and then examined the association of the identified loci with incident stroke in FHS. Five genes in the FOCM pathway (GNMT [p = 1.60 x 10(-63)], CBS [p = 3.15 x 10(-26)], CPS1 [p = 9.10 x 10(-13)], ALDH1L1 [p = 7.3 x 10(-13)] and PSPH [p = 1.17 x 10(-16)]) were strongly associated with the difference between pre- and post-methionine load test tHcy levels (Delta POST). Of these, one variant in the ALDH1L1 locus, rs2364368, was associated with incident ischemic stroke. Promoter analyses reveal genetic and epigenetic differences that may explain a direct effect on GNMT transcription and a downstream affect on methionine metabolism. Additionally, a genetic-score consisting of the five significant loci explains 13% of the variance of DPOST in FHS and 6% of the variance in VISP. Association between variants in FOCM genes with Delta POST suggest novel mechanisms that lead to differences in methionine metabolism, and possibly the epigenome, impacting disease risk. These data emphasize the importance of a concerted effort to understand regulators of one carbon metabolism as potential therapeutic targets.
C1 [Williams, Stephen R.; Chen, Fang; Keene, Keith L.; Chen, Wei-Min; Sale, Michele M.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA 22903 USA.
[Williams, Stephen R.] Univ Virginia, Cardiovasc Res Ctr, Charlottesville, VA USA.
[Yang, Qiong; Liu, Xuan; Beiser, Alexa] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Yang, Qiong] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
[Keene, Keith L.; Worrall, Bradford B.] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA.
[Keene, Keith L.] E Carolina Univ, Dept Biol, Greenville, NC USA.
[Keene, Keith L.] E Carolina Univ, Ctr Hlth Dispar Res, Greenville, NC USA.
[Jacques, Paul; Selhub, Jacob] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
[Jacques, Paul; Selhub, Jacob] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA.
[Weinstein, Galit; Wolf, Philip A.; Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Hsu, Fang-Chi] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA.
[Wang, Liewei] Mayo Clin, Coll Med, Dept Mol Pharmacol & Expt Therapeut, Rochester, MN USA.
[Bookman, Ebony] NHGRI, Bethesda, MD 20892 USA.
[Doheny, Kimberly F.; Zilka, Michelle] Johns Hopkins Univ, Ctr Inherited Dis Res, Baltimore, MD USA.
[Nelson, Sarah; Gogarten, Stephanie M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Worrall, Bradford B.] Univ Virginia, Dept Neurol, Charlottesville, VA USA.
[Sale, Michele M.] Univ Virginia, Dept Med, Charlottesville, VA USA.
[Sale, Michele M.] Univ Virginia, Dept Biochem & Mol Genet, Charlottesville, VA USA.
RP Williams, SR (reprint author), Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA 22903 USA.
EM ms5fe@eservices.virginia.edu
OI Seshadri, Sudha/0000-0001-6135-2622; Williams,
Stephen/0000-0003-2108-2757; Gogarten, Stephanie/0000-0002-7231-9745;
Beiser, Alexa/0000-0001-8551-7778
FU National Heart, Lung and Blood Institute's Framingham Heart Study
[N01-HC-25195]; National Institute of Neurological Disorders and Stroke
[NS17950]; National Heart, Lung and Blood Association [U01HL 096917];
National Institute of Aging [AG08122, AG033193]; Robert Dawson Evans
Endowment of the Department of Medicine at Boston University School of
Medicine; Boston Medical Center; National Human Genome Research
institute; Genomics and Randomized Trials Network [U01HG00516-03]
FX This work was supported by the dedication of the Framingham Heart Study
participants, the National Heart, Lung and Blood Institute's Framingham
Heart Study (Contract No. N01-HC-25195,
http://www.framinghamheartstudy.org/) and by grants from the National
Institute of Neurological Disorders and Stroke (NS17950,
www.ninds.nih.gov/), the National Heart, Lung and Blood Association
(U01HL 096917, www.nhlbi.nih.gov) and the National Institute of Aging
(AG08122, AG033193, www.nia.nih.gov). A portion of FHS computations were
using the Linux Cluster for Genetic Analysis (LinGA-II) funded by the
Robert Dawson Evans Endowment of the Department of Medicine at Boston
University School of Medicine and Boston Medical Center. Additionally,
VISP is supported by the National Human Genome Research institute and
the Genomics and Randomized Trials Network (U01HG00516-03,
http://www.genome.gov/27541119). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 55
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PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7390
EI 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD MAR
PY 2014
VL 10
IS 3
AR e1004214
DI 10.1371/journal.pgen.1004214
PG 13
WC Genetics & Heredity
SC Genetics & Heredity
GA AI8FM
UT WOS:000337144700039
PM 24651765
ER
PT J
AU Berlett, BS
Levine, RL
AF Berlett, Barbara S.
Levine, Rodney L.
TI Designing antioxidant peptides
SO REDOX REPORT
LA English
DT Article
DE Ionizing radiation; Radioprotection; Amino acid oxidation; Methionine;
Histidine
ID BACTERIUM DEINOCOCCUS-RADIODURANS; METHIONINE SULFOXIDE REDUCTASE;
ESCHERICHIA-COLI; GLUTAMINE-SYNTHETASE; AMINO-ACIDS;
RADIATION-RESISTANCE; IONIZING-RADIATION; HYDROGEN-PEROXIDE; PROTEIN
OXIDATION; GAMMA-RADIATION
AB Background: Ionizing radiation causes the generation of damaging reactive oxygen species that lead to cellular damage and death. Organisms such as Deinococcus radiodurans have evolved mechanisms for extreme resistance to ionizing radiation, and resistance has been shown to be a consequence of protection of critical proteins from oxidative inactivation.
Objectives: D. radiodurans accumulates high levels of manganese and of small peptides that together are protective. Our aim was to rationally design antioxidant peptides.
Methods: Amino acid analysis was utilized to determine the rates of loss of the 20 amino acids exposed to varying doses of irradiation. The activity of glutamine synthetase and methionine sulfoxide reductase was assayed to follow their inactivation by irradiation.
Results: The ability of an amino acid to protect enzymes from inactivation by ionizing radiation paralleled its sensitivity to ionizing radiation. Based on this observation and the ability of histidine to confer water solubility, we synthesized the hexapeptide His-Met-His-Met-His-Met and found that it provided markedly increased protection against irradiation.
Discussion: Small peptides containing histidine and methionine were readily soluble and provided enzymes with remarkable protection from inactivation by ionizing radiation.
C1 [Berlett, Barbara S.; Levine, Rodney L.] NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA.
RP Levine, RL (reprint author), NHLBI, Biochem Lab, NIH, Bldg 50,Room 2351, Bethesda, MD 20892 USA.
EM rlevine@nih.gov
RI Levine, Rodney/D-9885-2011
FU Intramural Research Program of the National Heart, Lung, and Blood
Institute
FX This research was supported by the Intramural Research Program of the
National Heart, Lung, and Blood Institute.
NR 39
TC 5
Z9 5
U1 2
U2 11
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1351-0002
EI 1743-2928
J9 REDOX REP
JI Redox Rep.
PD MAR
PY 2014
VL 19
IS 2
BP 80
EP 86
DI 10.1179/1351000213Y.0000000078
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AI8BQ
UT WOS:000337129800005
PM 24520968
ER
PT J
AU Miyagishima, KJ
Grunert, U
Li, W
AF Miyagishima, Kiyoharu J.
Gruenert, Ulrike
Li, Wei
TI Processing of S-cone signals in the inner plexiform layer of the
mammalian retina
SO VISUAL NEUROSCIENCE
LA English
DT Review
DE Color vision; Primate and nonprimate retina; Amacrine cell; Blue-ON
pathway; Blue-OFF pathway
ID NEW-WORLD MONKEY; MARMOSET CALLITHRIX-JACCHUS; LATERAL
GENICULATE-NUCLEUS; MIDGET GANGLION-CELLS; PRIMATE COLOR-VISION;
RECEPTIVE-FIELD STRUCTURE; DIFFUSE BIPOLAR CELLS; MACAQUE RETINA; RABBIT
RETINA; MOUSE RETINA
AB Color information is encoded by two parallel pathways in the mammalian retina. One pathway compares signals from long- and middle-wavelength sensitive cones and generates red-green opponency. The other compares signals from short- and middle-/long-wavelength sensitive cones and generates blue-green (yellow) opponency. Whereas both pathways operate in trichromatic primates (including humans), the fundamental, phylogenetically ancient color mechanism shared among most mammals is blue-green opponency. In this review, we summarize the current understanding of how signals from short-wavelength sensitive cones are processed in the primate and nonprimate mammalian retina, with a focus on the inner plexiform layer where bipolar, amacrine, and ganglion cell processes interact to facilitate the generation of blue-green opponency.
C1 [Miyagishima, Kiyoharu J.; Li, Wei] NEI, NIH, Bethesda, MD 20892 USA.
[Gruenert, Ulrike] Univ Sydney, Dept Ophthalmol, Sydney, NSW 2006, Australia.
[Gruenert, Ulrike] Univ Sydney, Save Sight Inst, Sydney, NSW 2006, Australia.
[Gruenert, Ulrike] Univ Sydney, Australian Res Council, Ctr Excellence Vis Sci, Sydney, NSW 2006, Australia.
RP Grunert, U (reprint author), Save Sight Inst, Sydney Eye Hosp Campus,GPO Box 4337, Bethesda, MD 20014 USA.
EM ugrunert@sydney.edu.au; liwei2@nei.nih.gov
RI Grunert, Ulrike/A-5194-2012
OI Grunert, Ulrike/0000-0002-9595-8152
FU National Health & Medical Research Council of Australia [632640,
1022609]; National Eye Institute (USA)
FX We would like to thank our colleagues and co-authors for their help. For
this review T. Chan, K. Ghosh, S. Lee, P. Martin, I. Telkes and H.
Wassle made important contributions. We would like to thank Heinz
Wassle, Paul Martin, Alexander Sher, and Steven DeVries for providing
images and Paul Martin for critically reading an earlier version of this
manuscript. This work was supported by Project Grants from the National
Health & Medical Research Council of Australia 632640 and 1022609 to UG,
and the National Eye Institute (USA) intramural research program to KJM
& WL.
NR 101
TC 10
Z9 10
U1 2
U2 9
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0952-5238
EI 1469-8714
J9 VISUAL NEUROSCI
JI Visual Neurosci.
PD MAR
PY 2014
VL 31
IS 2
SI SI
BP 153
EP 163
DI 10.1017/S0952523813000308
PG 11
WC Neurosciences; Ophthalmology
SC Neurosciences & Neurology; Ophthalmology
GA AI9YJ
UT WOS:000337303800004
PM 24016424
ER
PT J
AU Nieman, L
AF Nieman, Lynette
TI Pitfalls in the diagnosis and differential diagnosis of Cushing's
syndrome
SO CLINICAL ENDOCRINOLOGY
LA English
DT Editorial Material
ID MULTICENTER; DISEASE
C1 NICHD, NIH, RBMB, Bethesda, MD 20817 USA.
RP Nieman, L (reprint author), NICHD, NIH, RBMB, 8220 Hamilton Spring Ct, Bethesda, MD 20817 USA.
EM niemanl@nih.gov
FU Intramural NIH HHS [Z01 HD000638-14]
NR 8
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0300-0664
EI 1365-2265
J9 CLIN ENDOCRINOL
JI Clin. Endocrinol.
PD MAR
PY 2014
VL 80
IS 3
BP 333
EP 334
DI 10.1111/cen.12362
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AI8RW
UT WOS:000337193000004
PM 24303816
ER
PT J
AU Cappelle, J
Zhao, DL
Gilbert, M
Nelson, MI
Newman, SH
Takekawa, JY
Gaidet, N
Prosser, DJ
Liu, Y
Li, P
Shu, YL
Xiao, XM
AF Cappelle, Julien
Zhao, Delong
Gilbert, Marius
Nelson, Martha I.
Newman, Scott H.
Takekawa, John Y.
Gaidet, Nicolas
Prosser, Diann J.
Liu, Ying
Li, Peng
Shu, Yuelong
Xiao, Xiangming
TI Risks of Avian Influenza Transmission in Areas of Intensive Free-Ranging
Duck Production with Wild Waterfowl
SO ECOHEALTH
LA English
DT Article
DE avian influenza virus; wild birds; migration; interface; contact;
ecology; epidemiology; China; Poyang; telemetry; remote sensing; GPS
ID DOMESTIC DUCKS; H5N1 OUTBREAKS; POYANG LAKE; CLADE 2.3.2; VIRUS H5N1; A
VIRUSES; HONG-KONG; EXPERIMENTAL-INFECTION; SOUTHERN CHINA; BIRDS
AB For decades, southern China has been considered to be an important source for emerging influenza viruses since key hosts live together in high densities in areas with intensive agriculture. However, the underlying conditions of emergence and spread of avian influenza viruses (AIV) have not been studied in detail, particularly the complex spatiotemporal interplay of viral transmission between wild and domestic ducks, two major actors of AIV epidemiology. In this synthesis, we examine the risks of avian influenza spread in Poyang Lake, an area of intensive free-ranging duck production and large numbers of wild waterfowl. Our synthesis shows that farming of free-grazing domestic ducks is intensive in this area and synchronized with wild duck migration. The presence of juvenile domestic ducks in harvested paddy fields prior to the arrival and departure of migrant ducks in the same fields may amplify the risk of AIV circulation and facilitate the transmission between wild and domestic populations. We provide evidence associating wild ducks migration with the spread of H5N1 in the spring of 2008 from southern China to South Korea, Russia, and Japan, supported by documented wild duck movements and phylogenetic analyses of highly pathogenic avian influenza H5N1 sequences. We suggest that prevention measures based on a modification of agricultural practices may be implemented in these areas to reduce the intensity of AIV transmission between wild and domestic ducks. This would require involving all local stakeholders to discuss feasible and acceptable solutions.
C1 [Cappelle, Julien; Gaidet, Nicolas] CIRAD ES, UR AGIRs, F-34398 Montpellier 5, France.
[Cappelle, Julien; Zhao, Delong; Xiao, Xiangming] Univ Oklahoma, Ctr Spatial Anal, Dept Bot & Microbiol, Norman, OK 73019 USA.
[Cappelle, Julien] Inst Pasteur Cambodge, Epidemiol & Publ Hlth Unit, Phnom Penh, Cambodia.
[Gilbert, Marius] Univ Libre Brussels, B-1050 Brussels, Belgium.
[Gilbert, Marius] Fonds Natl Rech Sci, B-1000 Brussels, Belgium.
[Nelson, Martha I.] NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Newman, Scott H.] Vietnam Food & Agr Org United Nations FAO, Emergency Ctr Transboundary Anim Dis ECTAD Progra, Hanoi, Vietnam.
[Takekawa, John Y.] US Geol Survey, Western Ecol Res Ctr, San Francisco Bay Estuary Field Stn, Vallejo, CA USA.
[Prosser, Diann J.] US Geol Survey, Patuxent Wildlife Res Ctr, Beltsville, MD USA.
[Liu, Ying; Li, Peng] Jiangxi Normal Univ, Sch Geog & Environm, Nanchang, Peoples R China.
[Li, Peng] Chinese Acad Sci, Inst Geog Sci & Nat Resources Res, Beijing, Peoples R China.
[Shu, Yuelong] China CDC, Natl Inst Viral Dis Control & Prevent, Beijing, Peoples R China.
RP Cappelle, J (reprint author), CIRAD ES, UR AGIRs, TA C 22-E,Campus Int Baillarguet, F-34398 Montpellier 5, France.
EM julien.cappelle@cirad.fr
RI Gaidet, Niccolas/H-8122-2013;
OI Gilbert, Marius/0000-0003-3708-3359; Prosser, Diann/0000-0002-5251-1799
FU National Institutes of Health [NIH 1R01AI101028-01A1]; NIH Fogarty
International Center through the NSF/NIH Ecology of Infectious Diseases
program [R01-TW007869]; Food and Agriculture Organization of the United
Nations; U.S. Geological Survey; National Aeronautics and Space
Administration (NASA) Public Health Program [NNX11AF66G]; Gripavi
project - French Ministry of Foreign Affairs
FX This study was supported by a grant from the National Institutes of
Health (NIH 1R01AI101028-01A1), a grant from the NIH Fogarty
International Center (R01-TW007869) through the NSF/NIH Ecology of
Infectious Diseases program, the Food and Agriculture Organization of
the United Nations, the U.S. Geological Survey, and a grant from
National Aeronautics and Space Administration (NASA) Public Health
Program (NNX11AF66G). Julien Cappelle was supported by the Gripavi
project funded by the French Ministry of Foreign Affairs. We thank
Martine Duportal for her help in designing the figures and Isa Woo with
editorial assistance. The use of trade, product, or firm names in this
publication is for descriptive purposes only and does not imply
endorsement by the U.S. Government.
NR 45
TC 9
Z9 9
U1 5
U2 40
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1612-9202
EI 1612-9210
J9 ECOHEALTH
JI EcoHealth
PD MAR
PY 2014
VL 11
IS 1
BP 109
EP 119
DI 10.1007/s10393-014-0914-2
PG 11
WC Biodiversity Conservation; Ecology; Environmental Sciences
SC Biodiversity & Conservation; Environmental Sciences & Ecology
GA AI7MP
UT WOS:000337076000013
PM 24652313
ER
PT J
AU Gharwan, H
Sci, D
AF Gharwan, Helen
Groninger, Hunter
TI Targeted Cancer Therapies, Part 2 #277
SO JOURNAL OF PALLIATIVE MEDICINE
LA English
DT Editorial Material
ID ADVERSE-REACTIONS; ANTIBODIES; THERAPEUTICS; MANAGEMENT; TOXICITY
C1 [Groninger, Hunter] NIH, Pain & Palliat Care Serv, Clin Res Ctr, Bethesda, MD 20892 USA.
RP Sci, D (reprint author), NIH, Pain & Palliat Care Serv, Clin Res Ctr, Bldg 10,Room 2-1733,10 Ctr Dr, Bethesda, MD 20892 USA.
EM hunter.groninger@nih.gov
NR 10
TC 0
Z9 0
U1 0
U2 1
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1096-6218
EI 1557-7740
J9 J PALLIAT MED
JI J. Palliat. Med.
PD MAR
PY 2014
VL 17
IS 3
BP 358
EP 360
DI 10.1089/jpm.2014.9444
PG 3
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA AI6ZL
UT WOS:000337027700021
PM 24528156
ER
PT J
AU Glinskii, OV
Li, F
Wilson, LS
Barnes, S
Rittenhouse-Olson, K
Barchi, JJ
Pienta, KJ
Glinsky, VV
AF Glinskii, Olga V.
Li, Feng
Wilson, Landon S.
Barnes, Stephen
Rittenhouse-Olson, Kate
Barchi, Joseph J., Jr.
Pienta, Kenneth J.
Glinsky, Vladislav V.
TI Endothelial integrin alpha 3 beta 1 stabilizes carbohydrate-mediated
tumor/endothelial cell adhesion and induces macromolecular signaling
complex formation at the endothelial cell membrane
SO ONCOTARGET
LA English
DT Article
DE tumor metastasis; adhesion; Thomsen-Friedenreich antigen; galectin;
integrin
ID THOMSEN-FRIEDENREICH DISACCHARIDE; PROSTATE-CANCER METASTASIS;
TUMOR-CELL; MONOCLONAL-ANTIBODY; BONE METASTASIS; HUMAN BREAST;
IN-VITRO; GALECTIN-3; ANTIGEN; INHIBITOR
AB Blood borne metastatic tumor cell adhesion to endothelial cells constitutes a critical rate-limiting step in hematogenous cancer metastasis. Interactions between cancer associated carbohydrate Thomsen-Friedenreich antigen (TF-Ag) and endothelium-expressed galectin-3 (Gal-3) have been identified as the leading molecular mechanism initiating tumor/endothelial cell adhesion in several types of cancer. However, it is unknown how these rather weak and transient carbohydrate/lectin mediated interactions are stabilized. Here, using Western blot and LC tandem mass spectrometry analyses of pull-downs utilizing TF-Ag loaded gold nanoparticles, we identified Gal-3, endothelial integrin alpha 3 beta 1, Src kinase, as well as 5 additional molecules mapping onto focal adhesion pathway as parts of the macromolecular complexes formed at the endothelial cell membranes downstream of TF-Ag/Gal-3 interactions. In a modified parallel flow chamber assay, inhibiting a3 beta 1 integrin greatly reduced the strength of tumor/endothelial cell interactions without affecting the initial cancer cell adhesion. Further, the macromolecular complex induced by TF-Ag/Gal-3/alpha 3 beta 1 interactions activates Src kinase, p38, and ERK1/2, pathways in endothelial cells in a time- and alpha 3 beta 1-dependent manner. We conclude that, following the initial metastatic cell attachment to endothelial cells mediated by TF-Ag/Gal-3 interactions, endothelial integrin alpha 3 beta 1 stabilizes tumor/endothelial cell adhesion and induces the formation of macromolecular signaling complex activating several major signaling pathways in endothelial cells.
C1 [Glinskii, Olga V.; Li, Feng; Glinsky, Vladislav V.] Harry S Truman Mem Vet Hosp, Res Serv, Columbia, MO 65201 USA.
[Glinskii, Olga V.; Li, Feng; Glinsky, Vladislav V.] Univ Missouri, Sch Med, Dept Pathol & Anat Sci, Columbia, MO USA.
[Glinskii, Olga V.; Li, Feng; Glinsky, Vladislav V.] Univ Missouri, Sch Med, Dept Med Pharmacol & Physiol, Columbia, MO USA.
[Wilson, Landon S.; Barnes, Stephen] Univ Alabama Birmingham, Dept Pharmacol & Toxicol, Birmingham, AL USA.
[Wilson, Landon S.; Barnes, Stephen] Univ Alabama Birmingham, Targeted Metabol & Prote Lab, Birmingham, AL USA.
[Rittenhouse-Olson, Kate] SUNY Buffalo, Dept Biotech & Clin Lab Sci, Buffalo, NY 14260 USA.
[Rittenhouse-Olson, Kate] SUNY Buffalo, Dept Microbiol, Buffalo, NY 14260 USA.
[Barchi, Joseph J., Jr.] NCI, Biol Chem Lab, Ctr Canc Res, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA.
[Pienta, Kenneth J.] Johns Hopkins Sch Med, James Buchanan Brady Urol Inst, Dept Urol, Dept Oncol, Baltimore, MD USA.
[Pienta, Kenneth J.] Johns Hopkins Sch Med, James Buchanan Brady Urol Inst, Dept Urol, Dept Pharmacol & Mol Sci, Baltimore, MD USA.
RP Glinsky, VV (reprint author), Harry S Truman Mem Vet Hosp, Res Serv, Columbia, MO 65201 USA.
EM glinskiivl@health.missouri.edu
RI Barchi Jr., Joseph/N-3784-2014
FU Biomedical Laboratory Research & Development Service of the VA Office of
Research and Development [1I01BX000609]; National Cancer Institute of
the National Institutes of Health [R01CA160461]
FX This research was supported in parts by the Award Number 1I01BX000609
from the Biomedical Laboratory Research & Development Service of the VA
Office of Research and Development (VVG) and the National Cancer
Institute of the National Institutes of Health Award R01CA160461 (VVG).
The content is solely the responsibility of the authors and does not
necessarily represent the official views of the National Institutes of
Health, or VA Office of Research and Development.
NR 36
TC 9
Z9 9
U1 1
U2 5
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD MAR
PY 2014
VL 5
IS 5
BP 1382
EP 1389
PG 8
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA AI6EI
UT WOS:000336963200023
PM 24675526
ER
PT J
AU Mamessier, E
Song, JY
Eberle, FC
Pack, S
Drevet, C
Chetaille, B
Abdullaev, Z
Adelaide, J
Birnbaum, D
Chaffanet, M
Pittaluga, S
Roulland, S
Chott, A
Jaffe, ES
Nadel, B
AF Mamessier, Emilie
Song, Joo Y.
Eberle, Franziska C.
Pack, Svetlana
Drevet, Charlotte
Chetaille, Bruno
Abdullaev, Ziedulla
Adelaide, Jose
Birnbaum, Daniel
Chaffanet, Max
Pittaluga, Stefania
Roulland, Sandrine
Chott, Andreas
Jaffe, Elaine S.
Nadel, Bertrand
TI Early lesions of follicular lymphoma: a genetic perspective
SO HAEMATOLOGICA
LA English
DT Article
ID B-CELL LYMPHOMA; ACUTE LYMPHOBLASTIC-LEUKEMIA; IN-SITU LOCALIZATION;
SOMATIC MUTATIONS; CLONAL EVOLUTION; HODGKIN-LYMPHOMA; FUSION;
EXPRESSION; BLOOD; TRANSPLANTATION
AB The pathogenesis of follicular lymphoma is a multi-hit process progressing over many years through the accumulation of numerous genetic alterations. Besides the hallmark t(14;18), it is still unclear which other oncogenic hits contribute to the early steps of transformation and in which precursor stages these occur. To address this issue, we performed high-resolution comparative genomic hybridization microarrays on laser-capture micro-dissected cases of follicular lymphoma in situ (n=4), partial involvement by follicular lymphoma (n=4), and duodenal follicular lymphoma (n=4), assumed to represent, potentially, the earliest stages in the evolution of follicular lymphoma. Cases of reactive follicular hyperplasia (n=2), uninvolved areas from follicular lymphoma in situ lymph nodes, follicular lymphoma grade 1-2 (n=5) and follicular lymphoma grade 3A (n=5) were used as controls. Surprisingly, alterations involving several relevant (onco)genes were found in all entities, but at significantly lower proportions than in overt follicular lymphoma. While the number of alterations clearly assigns all these entities as precursors, the pattern of partial involvement by follicular lymphoma alterations was quantitatively and qualitatively closer to that of follicular lymphoma, indicating significant selective pressure in line with its faster rate of progression. Among the most notable alterations, we observed and validated deletions of 1p36 and gains of the 7p and 12q chromosomes and related oncogenes, which include some of the most recurrent oncogenic alterations in overt follicular lymphoma (TNFRSF14, EZH2, MLL2). By further delineating distinctive and hierarchical molecular and genetic features of early follicular lymphoma entities, our analysis underlines the importance of applying appropriate criteria for the differential diagnosis. It also provides a first set of candidates likely to be involved in the cascade of hits that pave the path of the various progression phases to follicular lymphoma development.
C1 [Mamessier, Emilie; Drevet, Charlotte; Roulland, Sandrine; Nadel, Bertrand] CIML, Marseille, France.
[Song, Joo Y.; Eberle, Franziska C.; Pack, Svetlana; Abdullaev, Ziedulla; Pittaluga, Stefania; Jaffe, Elaine S.] NIH, Pathol Lab, Bethesda, MD 20892 USA.
[Chetaille, Bruno] IPC, Pathol Lab, Marseille, France.
[Adelaide, Jose; Birnbaum, Daniel; Chaffanet, Max] IPC, Marseille, France.
[Chott, Andreas] Wilhelminenspital Stadt Wien, Inst Pathol & Microbiol, Vienna, Austria.
RP Jaffe, ES (reprint author), NIH, Pathol Lab, Bethesda, MD 20892 USA.
EM elainejaffe@nih.gov; nadel@ciml.univ-mrs.fr
RI Pack, Svetlana/C-2020-2014; Nadel, Bertrand/J-2197-2014;
OI Jaffe, Elaine/0000-0003-4632-0301
FU Institut National du Cancer (INCa); Association pour la Recherche sur le
Cancer (ARC); MedImmune's Strategic Collaboration to Fund; Conduct
Medical Science Research program, Canceropole PACA; Institut National de
la Sante et de la Recherche Medicale (INSERM); Centre National de la
Recherche Scientifique (CNRS); Center for Cancer Research, National
Cancer Institute, National Institutes of Health; Canceropole PACA
FX This work was funded by grants from the Institut National du Cancer
(INCa), the Association pour la Recherche sur le Cancer (ARC), a
MedImmune's Strategic Collaboration to Fund and Conduct Medical Science
Research program, Canceropole PACA, and institutional grants from the
Institut National de la Sante et de la Recherche Medicale (INSERM), the
Centre National de la Recherche Scientifique (CNRS) and Intramural
Research Program of the Center for Cancer Research, National Cancer
Institute, National Institutes of Health. EM and CD were recipients of
fellowships from the Institut National du Cancer (INCa), Canceropole
PACA, and MedImmune's Strategic Collaboration to Fund and Conduct
Medical Science Research program. We thank Shelley Hoover and Dr. Mark
Simpson for their support.
NR 49
TC 22
Z9 22
U1 0
U2 6
PU FERRATA STORTI FOUNDATION
PI PAVIA
PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
SN 0390-6078
J9 HAEMATOLOGICA
JI Haematologica
PD MAR
PY 2014
VL 99
IS 3
BP 481
EP 488
DI 10.3324/haematol.2013.094474
PG 8
WC Hematology
SC Hematology
GA AH6QF
UT WOS:000336255000018
PM 24162788
ER
PT J
AU Amable, L
Gavin, E
Kudo, K
Meng, E
Rocconi, RP
Shevde, LA
Reed, E
AF Amable, Lauren
Gavin, Elaine
Kudo, Kenji
Meng, Erhong
Rocconi, Rodney P.
Shevde, Lalita A.
Reed, Eddie
TI GLI1 upregulates C-JUN through a specific 130-kDa isoform
SO INTERNATIONAL JOURNAL OF ONCOLOGY
LA English
DT Article
DE Hedgehog; GLI1; AP1; C-JUN; cisplatin resistance
ID HEDGEHOG SIGNALING PATHWAY; MESSENGER-RNA EXPRESSION; OVARIAN-CANCER
CELLS; DNA-DAMAGE; STEM-CELL; REPAIR; ACTIVATION; GENES; TRANSCRIPTION;
INHIBITION
AB The Hedgehog pathway is molecularly linked to increased resistance to cisplatin and increased repair of platinum-DNA damage, through C-JUN. GLI1, which has five known isoforms, is a positive transcriptional regulator in Hedgehog. Southwestern blot assay, EMSA and ChIP assays indicate that only one of five isoforms of GLI1 may be responsible for the Hedgehog link with C-JUN and thus, increased platinum-DNA adduct repair. Cancer tissues express this 130-kDa isoform at levels 6-fold higher than non-malignant tissues; and this isoform exists in abundance in six of seven ovarian cancer cell lines examined.
C1 [Amable, Lauren; Reed, Eddie] Natl Inst Minor Hlth & Hlth Dispar, NIH, Bethesda, MD 20892 USA.
[Gavin, Elaine; Kudo, Kenji; Meng, Erhong; Rocconi, Rodney P.] Univ S Alabama, Mitchell Canc Inst, Mobile, AL 36604 USA.
[Shevde, Lalita A.] Univ Alabama Birmingham, Dept Pathol, Ctr Comprehens Canc, Birmingham, AL 35233 USA.
RP Reed, E (reprint author), Natl Inst Minor Hlth & Hlth Dispar, NIH, 3 Ctr Dr, Bethesda, MD 20892 USA.
EM eddie.reed@nih.gov
FU NIH, National Institute on Minority Health and Health Disparities
FX This study was supported by Intramural Research Program of the NIH,
National Institute on Minority Health and Health Disparities. We thank
Wesley Denny for his helpful discussions and technical assistance.
NR 26
TC 3
Z9 3
U1 0
U2 2
PU SPANDIDOS PUBL LTD
PI ATHENS
PA POB 18179, ATHENS, 116 10, GREECE
SN 1019-6439
EI 1791-2423
J9 INT J ONCOL
JI Int. J. Oncol.
PD MAR
PY 2014
VL 44
IS 3
BP 655
EP 661
DI 10.3892/ijo.2013.2222
PG 7
WC Oncology
SC Oncology
GA AI5GZ
UT WOS:000336894900003
PM 24366538
ER
PT J
AU Logan, JK
Walton-Diaz, A
Rais-Bahrami, S
Merino, MJ
Turkbey, B
Choyke, PL
Pinto, PA
AF Logan, Jennifer K.
Walton-Diaz, Annerleim
Rais-Bahrami, Soroush
Merino, Maria J.
Turkbey, Baris
Choyke, Peter L.
Pinto, Peter A.
TI Changes Observed in Multiparametric Prostate Magnetic Resonance Imaging
Characteristics Correlate With Histopathological Development of Chronic
Granulomatous Prostatitis After Intravesical Bacillus Calmette-Guerin
Therapy
SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY
LA English
DT Article
DE granulomatous prostatitis; intravesical BCG; prostate neoplasms;
magnetic resonance imaging; ultrasound
ID NEEDLE-ASPIRATION-CYTOLOGY; BLADDER-CANCER; IMMUNOTHERAPY; APPEARANCE
AB Administration of Bacillus Calmette-Guerin (BCG) has been shown to cause granulomatous prostatitis, a rare inflammatory process that can be mistaken for prostate cancer. We present a case of a 78-year-old man on active surveillance for prostate cancer with a subsequent diagnosis of high-grade urothelial carcinoma. After intravesical BCG therapy, he developed chronic granulomatous prostatitis. We present serial magnetic resonance imaging and biopsy data demonstrating the time interval between BCG administration and the manifestation of chronic granulomatous prostatitis.
C1 [Logan, Jennifer K.; Walton-Diaz, Annerleim; Rais-Bahrami, Soroush; Pinto, Peter A.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Merino, Maria J.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Turkbey, Baris; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
[Pinto, Peter A.] NCI, Ctr Intervent Oncol, NIH, Bethesda, MD 20892 USA.
RP Logan, JK (reprint author), NCI, Urol Oncol Branch, NIH, 10 Ctr Dr,MSC 1210,Bldg 10,CRC Room 2W-5940, Bethesda, MD 20892 USA.
EM jklogan@gmail.com
OI Rais-Bahrami, Soroush/0000-0001-9466-9925
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research; Center for Interventional Oncology; National Institutes
of Health
FX Supported by the Intramural Research Program of the National Institutes
of Health, National Cancer Institute, Center for Cancer Research, and
the Center for Interventional Oncology. National Institutes of Health
and Philips Healthcare have a cooperative research and development
agreement. National Institutes of Health and Philips share intellectual
property in the field. This research was also made possible through the
National Institutes of Health Medical Research Scholars Program, a
public-private partnership supported jointly by the National Institutes
of Health and generous contributions to the Foundation for the National
Institutes of Health from Pfizer Inc, The Leona M. and Harry B. Helmsley
Charitable Trust, and the Howard Hughes Medical Institute as well as
other private donors. For a complete list, please visit the Foundation
website at
http://www.fnih.org/work/programs-development/medical-research-scholars-
program.
NR 10
TC 3
Z9 4
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0363-8715
EI 1532-3145
J9 J COMPUT ASSIST TOMO
JI J. Comput. Assist. Tomogr.
PD MAR-APR
PY 2014
VL 38
IS 2
BP 274
EP 276
PG 3
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AI2YZ
UT WOS:000336726400021
PM 24637671
ER
PT J
AU Soliman, SE
Kovac, P
AF Soliman, Sameh E.
Kovac, Pavol
TI Practical Synthesis of Building Blocks for Oligosaccharides Containing
the beta-D-Galp-(1 -> 3)-beta-D-GlcpNAc Motif
SO SYNTHESIS-STUTTGART
LA English
DT Article
DE carbohydrates; oligosaccharides; synthetic methods; thioglycosides;
protecting groups
ID DISACCHARIDE; POLYSACCHARIDE; CONJUGATION; FRAGMENTS
AB An efficient, new pathway for the synthesis of the title sequence has been developed. The sequence has been obtained as a glycosyl donor, beta-D-Galp-(1 -> 3)-beta-D-GlcpNAc-1-SEt, or equipped with a linker (spacer) suitable for conjugation to other molecules, beta-D-Galp-(1 -> 3)-beta-D-GlcpNAc-1-(OCH2CH2)(3)N-3. Both disaccharides have been obtained in crystalline condition for the first time and fully characterized. The existing synthesis of the intermediate disaccharide glycosyl donor was improved by conducting the silver triflate mediated glycosylation under base-deficient conditions in the presence of 1,1,3,3-tetramethylurea and in the absence of molecular sieves.
C1 [Soliman, Sameh E.] Univ Alexandria, Fac Sci, Dept Chem, Alexandria 21321, Egypt.
[Soliman, Sameh E.; Kovac, Pavol] NIDDK, LBC, NIH, Bethesda, MD 20892 USA.
RP Kovac, P (reprint author), NIDDK, LBC, NIH, Bethesda, MD 20892 USA.
EM kpn@helix.nih.gov
RI Kovac, Pavol/B-8813-2008
OI Kovac, Pavol/0000-0001-5044-3449
FU NIH, NIDDK
FX This research was supported by the Intramural Research Program of the
NIH, NIDDK.
NR 12
TC 4
Z9 4
U1 1
U2 7
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0039-7881
EI 1437-210X
J9 SYNTHESIS-STUTTGART
JI Synthesis
PD MAR
PY 2014
VL 46
IS 6
BP 748
EP 751
DI 10.1055/s-0033-1340620
PG 4
WC Chemistry, Organic
SC Chemistry
GA AI4MD
UT WOS:000336838600004
ER
PT J
AU Kaiser, E
Wess, J
Tian, Q
Schroder, L
Kaestner, L
Lipp, P
AF Kaiser, E.
Wess, J.
Tian, Q.
Schroeder, L.
Kaestner, L.
Lipp, P.
TI Conditional and selective activation of the Gq pathway in the heart and
its impact on cardiac function in vivo
SO ACTA PHYSIOLOGICA
LA English
DT Meeting Abstract
C1 [Kaiser, E.; Tian, Q.; Schroeder, L.; Kaestner, L.; Lipp, P.] Univ Saarland, Fac Med, Homburg, Germany.
[Wess, J.] Natl Inst Diabet & Digest & Kidney Dis, Lab Bioorgan Chem, Bethesda, MD USA.
RI Kaestner, Lars/P-6988-2016
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1748-1708
EI 1748-1716
J9 ACTA PHYSIOL
JI Acta Physiol.
PD MAR
PY 2014
VL 210
SU 695
BP 94
EP 96
PG 2
WC Physiology
SC Physiology
GA AC1MP
UT WOS:000332259900239
ER
PT J
AU Evans, JD
Aizenstein, H
Petrides, G
Gunning, F
AF Evans, Jovier D.
Aizenstein, Howard
Petrides, Georgios
Gunning, Faith
TI INTEGRATING NEUROIMAGING INTO CLINICAL TRIALS: OPPORTUNITIES &
CHALLENGES
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry
(AAGP)
CY MAR, 2014
CL Orlando, FL
SP Amer Assoc Geriatr Psychiat
C1 [Evans, Jovier D.] NIMH, Bethesda, MD 20892 USA.
[Aizenstein, Howard] Univ Pittsburgh, Pttsburgh, PA USA.
[Petrides, Georgios] Northsore LIJ Hlth Syst, Zucker Hillside Hosp, Glen Oaks, NY USA.
[Gunning, Faith] Weill Cornell Med Coll, White Plains, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2014
VL 22
IS 3
SU S
BP S20
EP S21
PG 2
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA AH4FE
UT WOS:000336081800023
ER
PT J
AU Lavretsky, H
Wagster, MV
Evans, JD
Niederehe, G
AF Lavretsky, Helen
Wagster, Molly V.
Evans, Jovier D.
Niederehe, George
TI SENIOR INVESTIGATOR WORKSHOP ON THE NEW NIH POLICIES FOR RESEARCH
FUNDING AND PROGRAM OPPORTUNITIES
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry
(AAGP)
CY MAR, 2014
CL Orlando, FL
SP Amer Assoc Geriatr Psychiat
C1 [Lavretsky, Helen] Univ Calif Los Angeles, Los Angeles, CA USA.
[Wagster, Molly V.; Evans, Jovier D.; Niederehe, George] NIH, Bethesda, MD 20892 USA.
RI Lavretsky, Helen/M-5711-2015
OI Lavretsky, Helen/0000-0001-9990-5085
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2014
VL 22
IS 3
SU S
BP S30
EP S30
PG 1
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA AH4FE
UT WOS:000336081800037
ER
PT J
AU Niederehe, G
Yaffe, K
Bogner, HR
Bromberger, JT
AF Niederehe, George
Yaffe, Kristine
Bogner, Hillary R.
Bromberger, Joyce T.
TI TRAJECTORIES OF RISK AND SYMPTOM EXPRESSION IN LATE LIFE DEPRESSION
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry
(AAGP)
CY MAR, 2014
CL Orlando, FL
SP Amer Assoc Geriatr Psychiat
C1 [Niederehe, George] NIMH, Bethesda, MD 20892 USA.
[Bogner, Hillary R.] Univ Penn, Philadelphia, PA 19104 USA.
[Yaffe, Kristine] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Bromberger, Joyce T.] Univ Pittsburgh, Pittsburgh, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2014
VL 22
IS 3
SU S
BP S35
EP S35
PG 1
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA AH4FE
UT WOS:000336081800045
ER
PT J
AU Widemann, BC
Acosta, MT
Ammoun, S
Belzberg, AJ
Bernards, A
Blakeley, J
Bretscher, A
Cichowski, K
Clapp, DW
Dombi, E
Evans, GD
Ferner, R
Fernandez-Valle, C
Fisher, MJ
Giovannini, M
Gutmann, DH
Hanemann, CO
Hennigan, R
Huson, S
Ingram, D
Kissil, J
Korf, BR
Legius, E
Packer, RJ
McClatchey, AI
McCormick, F
North, K
Pehrsson, M
Plotkin, SR
Ramesh, V
Ratner, N
Schirmer, S
Sherman, L
Schorry, E
Stevenson, D
Stewart, DR
Ullrich, N
Bakker, AC
Morrison, H
AF Widemann, Brigitte C.
Acosta, Maria T.
Ammoun, Sylvia
Belzberg, Allan J.
Bernards, Andre
Blakeley, Jaishri
Bretscher, Antony
Cichowski, Karen
Clapp, D. Wade
Dombi, Eva
Evans, Gareth D.
Ferner, Rosalie
Fernandez-Valle, Cristina
Fisher, Michael J.
Giovannini, Marco
Gutmann, David H.
Hanemann, C. Oliver
Hennigan, Robert
Huson, Susan
Ingram, David
Kissil, Joe
Korf, Bruce R.
Legius, Eric
Packer, Roger J.
McClatchey, Andrea I.
McCormick, Frank
North, Kathryn
Pehrsson, Minja
Plotkin, Scott R.
Ramesh, Vijaya
Ratner, Nancy
Schirmer, Susann
Sherman, Larry
Schorry, Elizabeth
Stevenson, David
Stewart, Douglas R.
Ullrich, Nicole
Bakker, Annette C.
Morrison, Helen
TI CTF Meeting 2012: Translation of the Basic Understanding of the Biology
and Genetics of NF1, NF2, and Schwannomatosis Toward the Development of
Effective Therapies
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
DE neurofibromatosis type 1; neurofibromatosis type 2; NF1; NF2;
schwannomatosis; tumor suppressor; SMARCB1; merlin neurofibromin;
preclinical models
ID HISTONE DEACETYLASE INHIBITOR; NEUROFIBROMATOSIS TYPE-2; VESTIBULAR
SCHWANNOMAS; FAMILIAL SCHWANNOMATOSIS; SPORADIC SCHWANNOMATOSIS;
RETROSPECTIVE ANALYSIS; MULTIPLE MENINGIOMAS; DIAGNOSTIC-CRITERIA;
SMARCB1 MUTATIONS; CLINICAL ARTICLE
AB The neurofibromatoses (NF) are autosomal dominant genetic disorders that encompass the rare diseases NF1, NF2, and schwannomatosis. The NFs affect more people worldwide than Duchenne muscular dystrophy and Huntington's disease combined. NF1 and NF2 are caused by mutations of known tumor suppressor genes (NF1 and NF2, respectively). For schwannomatosis, although mutations in SMARCB1 were identified in a subpopulation of schwannomatosis patients, additional causative gene mutations are still to be discovered. Individuals with NF1 may demonstrate manifestations in multiple organ systems, including tumors of the nervous system, learning disabilities, and physical disfigurement. NF2 ultimately can cause deafness, cranial nerve deficits, and additional severe morbidities caused by tumors of the nervous system. Unmanageable pain is a key finding in patients with schwannomatosis. Although today there is no marketed treatment for NF-related tumors, a significant number of clinical trials have become available. In addition, significant preclinical efforts have led to a more rational selection of potential drug candidates for NF trials. An important element in fueling this progress is the sharing of knowledge. For over 20 years the Children's Tumor Foundation has convened an annual NF Conference, bringing together NF professionals to share novel findings, ideas, and build collaborations. The 2012 NF Conference held in New Orleans hosted over 350 NF researchers and clinicians. This article provides a synthesis of the highlights presented at the conference and as such, is a state-of-the-field for NF research in 2012. (c) 2014 Wiley Periodicals, Inc.
C1 [Widemann, Brigitte C.; Dombi, Eva] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Acosta, Maria T.; Packer, Roger J.] Gilbert NF Inst, Washington, DC USA.
[Ammoun, Sylvia; Hanemann, C. Oliver] Univ Plymouth, Peninsula Sch Med, Plymouth PL4 8AA, Devon, England.
[Ammoun, Sylvia; Hanemann, C. Oliver] Univ Plymouth, Peninsula Sch Dent, Plymouth PL4 8AA, Devon, England.
[Belzberg, Allan J.; Blakeley, Jaishri] Johns Hopkins Univ, Baltimore, MD USA.
[Bernards, Andre; McClatchey, Andrea I.; Plotkin, Scott R.; Ramesh, Vijaya] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA.
[Bernards, Andre; McClatchey, Andrea I.; Plotkin, Scott R.; Ramesh, Vijaya] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA.
[Bretscher, Antony] Cornell Univ, New York, NY 10021 USA.
[Cichowski, Karen] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Clapp, D. Wade; Ingram, David] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
[Evans, Gareth D.; Huson, Susan] Univ Manchester, St Marys Hosp, Manchester M13 0JH, Lancs, England.
[Ferner, Rosalie] Guys & St Thomas NHS Fdn Trust, London, England.
[Ferner, Rosalie] Kings Coll London, Dept Clin Neurosci, London, England.
[Fernandez-Valle, Cristina] Univ Cent Florida, Orlando, FL 32816 USA.
[Fisher, Michael J.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Giovannini, Marco] Univ So Calif, House Res Inst, Los Angeles, CA USA.
[Gutmann, David H.] Washington Univ, Sch Med, St Louis, MO USA.
[Hennigan, Robert; Ratner, Nancy; Schorry, Elizabeth] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
[Kissil, Joe] Scripps Res Inst Florida, Jupiter, FL USA.
[Korf, Bruce R.] Univ Alabama Birmingham, Birmingham, AL USA.
[Legius, Eric] Catholic Univ Louvain, B-3000 Louvain, Belgium.
[McCormick, Frank] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[North, Kathryn] Childrens Hosp, Westmead, NSW, Australia.
[Pehrsson, Minja] Biomed Helsinki, Helsinki, Finland.
[Schirmer, Susann; Morrison, Helen] Leibniz Inst Age Res, Jena, Germany.
[Sherman, Larry] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Stevenson, David] Univ Utah, Salt Lake City, UT USA.
[Stewart, Douglas R.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Ullrich, Nicole] Childrens Hosp, Boston, MA 02115 USA.
[Bakker, Annette C.] Childrens Tumor Fdn, New York, NY 10005 USA.
RP Bakker, AC (reprint author), Childrens Tumor Fdn, 95 Pine St, New York, NY 10005 USA.
EM widemanb@mail.nih.gov; abakker@ctf.org
RI North, Kathryn/K-6476-2012; Morrison, Helen/B-3984-2017;
OI North, Kathryn/0000-0003-0841-8009; Morrison, Helen/0000-0003-4938-1409;
Hanemann, Clemens Oliver/0000-0002-1951-1025; Evans,
Gareth/0000-0002-8482-5784
FU National Institutes of Health Grant Award [1R13NS070505-01]; Center for
Cancer Research; National Cancer Institute
FX Grant sponsor: National Institutes of Health Grant Award; Grant number:
1R13NS070505-01; Grant sponsor: Center for Cancer Research; Grant
sponsor: National Cancer Institute.
NR 70
TC 4
Z9 4
U1 0
U2 15
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4825
EI 1552-4833
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD MAR
PY 2014
VL 164
IS 3
BP 563
EP 578
DI 10.1002/ajmg.a.36312
PG 16
WC Genetics & Heredity
SC Genetics & Heredity
GA AB7NZ
UT WOS:000331978700001
PM 24443315
ER
PT J
AU Vanderver, A
Tonduti, D
Kahn, I
Schmidt, J
Medne, L
Vento, J
Chapman, KA
Lanpher, B
Pearl, P
Gropman, A
Lourenco, C
Bamforth, JS
Sharpe, C
Pineda, M
Schallner, J
Bodamer, O
Orcesi, S
Oberstein, SAJL
Sistermans, EA
Yntema, HG
Bonnemann, C
Waldman, AT
van der Knaap, MS
AF Vanderver, Adeline
Tonduti, Davide
Kahn, Ilana
Schmidt, Johanna
Medne, Livija
Vento, Jodie
Chapman, Kimberly A.
Lanpher, Brendan
Pearl, Phillip
Gropman, Andrea
Lourenco, Charles
Bamforth, John-Steven
Sharpe, Cynthia
Pineda, Mercedes
Schallner, Jens
Bodamer, Olaf
Orcesi, Simona
Oberstein, Saskia A. J. Lesnik
Sistermans, Erik A.
Yntema, Helger G.
Bonnemann, Carsten
Waldman, Amy T.
van der Knaap, Marjo S.
TI Characteristic Brain Magnetic Resonance Imaging Pattern in Patients With
Macrocephaly and PTEN Mutations
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
DE macrocephaly; perivascular; autism spectrum disorder; magnetic resonance
imaging; genetics; PTEN; hamartoma; leukoencephalopathy
ID RILEY-RUVALCABA-SYNDROME; AUTISM SPECTRUM DISORDERS;
LHERMITTE-DUCLOS-DISEASE; COWDEN-SYNDROME; PROTEUS SYNDROME; GERMLINE;
TUMOR; GENE; HYPOMELANOSIS; PREVALENCE
AB We describe an MRI phenotype seen in a series of patients with mutations in PTEN who have clinical features consistent with PTEN hamartoma tumor syndrome (PHTS). Retrospective review of clinical data and MRI was performed in 23 subjects evaluated in four different tertiary care centers with clinical programs in inherited disorders of the white matter. Patients were referred due to abnormal MRI features and abnormal PTEN sequencing was identified. All subjects had significant macrocephaly (on average >4 SD above the mean), developmental delay with or without autism spectrum disorder and uniform MRI features of enlarged perivascular spaces and multifocal periventricular white matter abnormalities. The phenotype of PHTS may include MRI abnormalities such as multifocal periventricular white matter abnormalities and enlarged perivascular spaces. These neuroimaging findings, in association with macrocephaly and developmental delay, should prompt consideration of PTEN as a diagnostic possibility. (c) 2013 Wiley Periodicals, Inc.
C1 [Vanderver, Adeline; Schmidt, Johanna; Pearl, Phillip; Gropman, Andrea] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA.
[Tonduti, Davide] Univ Pavia, Dept Brain & Behav Sci, Child Neuropsychiat Unit, I-27100 Pavia, Italy.
[Kahn, Ilana] Childrens Natl Med Ctr, Dept Pediat, Washington, DC 20010 USA.
[Medne, Livija; Waldman, Amy T.] Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19104 USA.
[Vento, Jodie] Childrens Hosp Pittsburgh, UPMC, Div Child Neurol, Pittsburgh, PA 15213 USA.
[Chapman, Kimberly A.; Lanpher, Brendan] Childrens Natl Med Ctr, Dept Genet, Washington, DC 20010 USA.
[Lourenco, Charles] Univ Sao Paulo, Clin Hosp Ribeirao Preto, Neurogenet Unit, Sao Paulo, Brazil.
[Bamforth, John-Steven] Univ Alberta Hosp, Med Genet Clin, Edmonton, AB T6G 2B7, Canada.
[Sharpe, Cynthia] Starship Childrens Hosp, Paediat Neurol, Auckland, New Zealand.
[Pineda, Mercedes] Hosp San Juan Dios, Barcelona, Spain.
[Schallner, Jens] Uniklin Dresden, Klin & Poliklin Kinder & Jugendmed, Dresden, Germany.
[Bodamer, Olaf] Univ Miami, Miller Sch Med, Dept Human Genet, Miami, FL 33136 USA.
[Orcesi, Simona] C Mondino Natl Neurol Inst, Child Neurol & Psychiat Unit, Pavia, Italy.
[Oberstein, Saskia A. J. Lesnik] Leiden Univ, Med Ctr, Dept Clin Genet, Leiden, Netherlands.
[Sistermans, Erik A.] Vrije Univ Amsterdam, Med Ctr, Dept Clin Genet, Amsterdam, Netherlands.
[Yntema, Helger G.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands.
[Bonnemann, Carsten] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA.
[van der Knaap, Marjo S.] Vrije Univ Amsterdam, Med Ctr, Dept Child Neurol, Amsterdam, Netherlands.
RP Vanderver, A (reprint author), Childrens Natl Med Ctr, 111 Michigan Ave,NW, Washington, DC 20010 USA.
EM avanderv@childrensnational.org
RI Yntema, H.G./L-4771-2015; Lesnik Oberstein, Saskia/C-3643-2016; tonduti,
davide/K-1673-2016;
OI tonduti, davide/0000-0001-9371-7454; Sistermans,
Erik/0000-0001-7187-4563
FU Myelin Disorders Bioregistry Project
FX Grant sponsor: Myelin Disorders Bioregistry Project.
NR 32
TC 12
Z9 12
U1 3
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4825
EI 1552-4833
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD MAR
PY 2014
VL 164
IS 3
BP 627
EP 633
DI 10.1002/ajmg.a.36309
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA AB7NZ
UT WOS:000331978700008
PM 24375884
ER
PT J
AU Beaulieu, LM
Lin, E
Mick, E
Koupenova, M
Weinberg, EO
Kramer, CD
Genco, CA
Tanriverdi, K
Larson, MG
Benjamin, EJ
Freedman, JE
AF Beaulieu, Lea M.
Lin, Elaine
Mick, Eric
Koupenova, Milka
Weinberg, Ellen O.
Kramer, Carolyn D.
Genco, Caroline A.
Tanriverdi, Kahraman
Larson, Martin G.
Benjamin, Emelia J.
Freedman, Jane E.
TI Interleukin 1 Receptor 1 and Interleukin 1 beta Regulate Megakaryocyte
Maturation, Platelet Activation, and Transcript Profile During
Inflammation in Mice and Humans
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE blood platelets; diet; high-fat; IL1R1 protein; human; infection;
megakaryocytes
ID HIGH-FAT DIET; CYTOKINE PRODUCTION; CELLS; EXPRESSION; ATHEROSCLEROSIS;
IL-1-BETA; THROMBOPOIESIS; CANAKINUMAB; INHIBITION; ARTERIES
AB Objective Interleukin 1 Receptor 1 (IL1R1) and its ligand, IL1, are upregulated in cardiovascular disease, obesity, and infection. Previously, we reported a higher level of IL1R1 transcripts in platelets from obese individuals of the Framingham Heart Study (FHS), but its functional effect in platelets has never been described. Additionally, IL1 levels are increased in atherosclerotic plaques and in bacterial infections. The aim of this work is to determine whether IL1, through IL1R1, can activate platelets and megakaryocytes to promote atherothrombosis.
Approach and Results We found that IL1-related genes from platelets, as measured in 1819 FHS participants, were associated with increased body mass index, and a direct relationship was shown in wild-type mice fed a high-fat diet. Mechanistically, IL1 activated nuclear factor-B and mitogen-activated protein kinase signaling pathways in megakaryocytes. IL1, through IL1R1, increased ploidy of megakaryocytes to 64+ N by 2-fold over control. IL1 increased agonist-induced platelet aggregation by 1.2-fold with thrombin and 4.2-fold with collagen. IL1 increased adhesion to both collagen and fibrinogen, and heterotypic aggregation by 1.9-fold over resting. High fat diet-enhanced platelet adhesion was absent in IL1R1(-/-) mice. Wild-type mice infected with Porphyromonas gingivalis had circulating heterotypic aggregates (1.5-fold more than control at 24 hours and 6.2-fold more at 6 weeks) that were absent in infected IL1R1(-/-) and IL1(-/-) mice.
Conclusions In summary, IL1R1- and IL1-related transcripts are elevated in the setting of obesity. IL1R1/IL1 augment both megakaryocyte and platelet functions, thereby promoting a prothrombotic environment during infection and obesity; potentially contributing to the development of atherothrombotic disease.
C1 [Beaulieu, Lea M.; Koupenova, Milka; Tanriverdi, Kahraman; Freedman, Jane E.] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01605 USA.
[Mick, Eric] Univ Massachusetts, Sch Med, Worcester, MA 01605 USA.
[Lin, Elaine; Koupenova, Milka; Weinberg, Ellen O.; Kramer, Carolyn D.; Genco, Caroline A.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Framingham, MA USA.
[Genco, Caroline A.] Boston Univ, Sch Med, Infect Dis Sect, Framingham, MA USA.
[Genco, Caroline A.] Boston Univ, Sch Med, Dept Microbiol, Framingham, MA USA.
[Larson, Martin G.; Benjamin, Emelia J.] NHLBI, Framingham, MA USA.
[Larson, Martin G.; Benjamin, Emelia J.] Boston Univ, Framingham Heart Inst, Framingham, MA USA.
[Larson, Martin G.] Boston Univ, Dept Math & Stat, Framingham, MA USA.
RP Beaulieu, LM (reprint author), Univ Massachusetts, Sch Med, 368 Plantat St,ACS7-1012, Worcester, MA 01605 USA.
EM lea.beaulieu@umassmed.edu
FU National Institute of Allergy and Infectious Disease [P01 AI078894];
National Heart, Lung, and Blood Institute [HL087201, RFA-HL-12-008,
N01-HC 25195, 1R01AG028321, T32 HL07224]; National Institutes of Health
FX This work was supported by grants from the National Institutes of
Health, including the National Institute of Allergy and Infectious
Disease (P01 AI078894 to L. M. Beaulieu, E.O. Weinberg, C. D. Kramer, C.
A. Genco, and J.E. Freedman) and the National Heart, Lung, and Blood
Institute (HL087201 and RFA-HL-12-008 to J.E. Freedman, N01-HC 25195 and
1R01AG028321 to E.J. Benjamin, and T32 HL07224 to L. M. Beaulieu, M.
Koupenova, and C. D. Kramer).
NR 42
TC 23
Z9 25
U1 2
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1079-5642
EI 1524-4636
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD MAR
PY 2014
VL 34
IS 3
BP 552
EP 564
DI 10.1161/ATVBAHA.113.302700
PG 13
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA AD1LX
UT WOS:000332996600012
PM 24458711
ER
PT J
AU Shao, Z
Fu, ZJ
Stahl, A
Joyal, JS
Hatton, C
Juan, A
Hurst, C
Evans, L
Cui, ZH
Pei, D
Gong, Y
Xu, D
Tian, K
Bogardus, H
Edin, ML
Lih, F
Sapieha, P
Chen, J
Panigrahy, D
Hellstrom, A
Zeldin, DC
Smith, LEH
AF Shao, Zhuo
Fu, Zhongjie
Stahl, Andreas
Joyal, Jean-Sebastien
Hatton, Colman
Juan, Aimee
Hurst, Christian
Evans, Lucy
Cui, Zhenghao
Pei, Dorothy
Gong, Yan
Xu, Dan
Tian, Katherine
Bogardus, Hannah
Edin, Matthew L.
Lih, Fred
Sapieha, Przemyslaw
Chen, Jing
Panigrahy, Dipak
Hellstrom, Ann
Zeldin, Darryl C.
Smith, Lois E. H.
TI Cytochrome P450 2C8 omega 3-Long-Chain Polyunsaturated Fatty Acid
Metabolites Increase Mouse Retinal Pathologic Neovascularization-Brief
Report
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE angiogenesis factor; cytochrome P450 CYP2C8 (human); pathologic
neovascularization
ID OXYGEN-INDUCED RETINOPATHY; SOLUBLE EPOXIDE HYDROLASE; ENDOTHELIAL
EXPRESSION; UNITED-STATES; ANGIOGENESIS; METASTASIS; GROWTH; MODEL;
MICE; PREVALENCE
AB Objective Regulation of angiogenesis is critical for many diseases. Specifically, pathological retinal neovascularization, a major cause of blindness, is suppressed with dietary 3-long-chain polyunsaturated fatty acids (3LCPUFAs) through antiangiogenic metabolites of cyclooxygenase and lipoxygenase. Cytochrome P450 epoxygenases (CYP2C8) also metabolize LCPUFAs, producing bioactive epoxides, which are inactivated by soluble epoxide hydrolase (sEH) to transdihydrodiols. The effect of these enzymes and their metabolites on neovascularization is unknown.
Approach and Results The mouse model of oxygen-induced retinopathy was used to investigate retinal neovascularization. We found that CYP2C (localized in wild-type monocytes/macrophages) is upregulated in oxygen-induced retinopathy, whereas sEH is suppressed, resulting in an increased retinal epoxide:diol ratio. With a 3LCPUFA-enriched diet, retinal neovascularization increases in Tie2-driven human-CYP2C8-overexpressing mice (Tie2-CYP2C8-Tg), associated with increased plasma 19,20-epoxydocosapentaenoic acid and retinal epoxide:diol ratio. 19,20-Epoxydocosapentaenoic acids and the epoxide:diol ratio are decreased with overexpression of sEH (Tie2-sEH-Tg). Overexpression of CYP2C8 or sEH in mice does not change normal retinal vascular development compared with their wild-type littermate controls. The proangiogenic role in retina of CYP2C8 with both 3LCPUFA and 6LCPUFA and antiangiogenic role of sEH in 3LCPUFA metabolism were corroborated in aortic ring assays.
Conclusions Our results suggest that CYP2C 3LCPUFA metabolites promote retinal pathological angiogenesis. CYP2C8 is part of a novel lipid metabolic pathway influencing retinal neovascularization.
C1 [Shao, Zhuo; Fu, Zhongjie; Joyal, Jean-Sebastien; Hatton, Colman; Juan, Aimee; Hurst, Christian; Evans, Lucy; Cui, Zhenghao; Pei, Dorothy; Gong, Yan; Xu, Dan; Tian, Katherine; Bogardus, Hannah; Chen, Jing; Smith, Lois E. H.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston Childrens Hosp, Boston, MA USA.
[Pei, Dorothy] Harvard Univ, Sch Med, Dept Pathol, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA.
[Stahl, Andreas] Univ Eye Hosp Freiburg, Freiburg, Germany.
[Edin, Matthew L.; Lih, Fred; Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA.
[Sapieha, Przemyslaw] Univ Montreal, Dept Ophthalmol, Hop Maisonneuve Rosemont, Montreal, PQ, Canada.
[Hellstrom, Ann] Univ Gothenburg, Dept Ophthalmol, Sahlgrenska Acad, Gothenburg, Sweden.
RP Smith, LEH (reprint author), Boston Childrens Hosp, Dept Ophthalmol, 300 Longwood Ave, Boston, MA 02115 USA.
EM Lois.Smith@childrens.harvard.edu
FU National Institutes of Health (NIH)/National Eye Institute [EY022275,
EY017017, P01HD18655]; RPB Senior Investigator Award; Lowy Medical
Foundation; European Commission [305485]; Canadian Institute of Health
Research; BrightFocus Foundation; BCH Faculty Career Development Award;
Canada Research Chair tier II; Deutsche Ophthalmologische Gesellschaft;
Freifrau von Nauendorff Foundation; NCI [RO1CA148633-01A4]; NIH,
National Institute of Environmental Health Sciences [Z01025034]
FX This work was supported by the National Institutes of Health
(NIH)/National Eye Institute (EY022275, EY017017, and P01HD18655), RPB
Senior Investigator Award, Lowy Medical Foundation, European Commission
FP7 project 305485 PREVENT-ROP (LEHS), Canadian Institute of Health
Research (Z. Shao), BrightFocus Foundation and BCH Faculty Career
Development Award (J. Chen), Canada Research Chair tier II. (P.
Sapieha), Deutsche Ophthalmologische Gesellschaft and Freifrau von
Nauendorff Foundation (A. Stahl), NCI RO1CA148633-01A4 (D. Panigrahy)
and supported, in part, by the Intramural Research Program of the NIH,
National Institute of Environmental Health Sciences (Z01025034; D. C.
Zeldin).
NR 28
TC 14
Z9 14
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1079-5642
EI 1524-4636
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD MAR
PY 2014
VL 34
IS 3
BP 581
EP 586
DI 10.1161/ATVBAHA.113.302927
PG 6
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA AD1LX
UT WOS:000332996600015
PM 24458713
ER
PT J
AU Albert, PS
Liu, AY
Nansel, T
AF Albert, Paul S.
Liu, Aiyi
Nansel, Tonja
TI Efficient Logistic Regression Designs under an Imperfect Population
Identifier
SO BIOMETRICS
LA English
DT Article
DE Case-control designs; Diagnostic accuracy; Epidemiologic designs;
Misclassification; Measurement error
ID MISCLASSIFICATION; INTERVENTION; ACCURACY; 2-PHASE; TRIAL
AB Motivated by actual study designs, this article considers efficient logistic regression designs where the population is identified with a binary test that is subject to diagnostic error. We consider the case where the imperfect test is obtained on all participants, while the gold standard test is measured on a small chosen subsample. Under maximum-likelihood estimation, we evaluate the optimal design in terms of sample selection as well as verification. We show that there may be substantial efficiency gains by choosing a small percentage of individuals who test negative on the imperfect test for inclusion in the sample (e.g., verifying 90% test-positive cases). We also show that a two-stage design may be a good practical alternative to a fixed design in some situations. Under optimal and nearly optimal designs, we compare maximum-likelihood and semi-parametric efficient estimators under correct and misspecified models with simulations. The methodology is illustrated with an analysis from a diabetes behavioral intervention trial.
C1 [Albert, Paul S.; Liu, Aiyi] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Intramural Populat Hlth Res, Bethesda, MD 20892 USA.
[Nansel, Tonja] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Hlth Behav Branch, Div Intramural Populat Hlth Res, Bethesda, MD 20892 USA.
RP Albert, PS (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Intramural Populat Hlth Res, 6100 Execut Blvd,Room 7B05, Bethesda, MD 20892 USA.
EM albertp@mail.nih.gov
OI Nansel, Tonja/0000-0002-8298-7595; Liu, Aiyi/0000-0002-6618-5082
FU National Institutes of Health Eunice Kennedy Shriver National Institute
of Child Health and Human Development
FX We thank the Editor, Associate Editor, and Referee for constructive
comments that led to an improved paper. We thank the Center for
Information Technology, National Institutes of Health, for providing
access to the high-performance computational capabilities of the Biowulf
cluster computing system. This research was supported by the Intramural
Research Program of the National Institutes of Health Eunice Kennedy
Shriver National Institute of Child Health and Human Development.
NR 23
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0006-341X
EI 1541-0420
J9 BIOMETRICS
JI Biometrics
PD MAR
PY 2014
VL 70
IS 1
BP 175
EP 184
DI 10.1111/biom.12106
PG 10
WC Biology; Mathematical & Computational Biology; Statistics & Probability
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
Biology; Mathematics
GA AC4BS
UT WOS:000332466200019
PM 24261471
ER
PT J
AU Mitchell, EM
Lyles, RH
Manatunga, AK
Danaher, M
Perkins, NJ
Schisterman, EF
AF Mitchell, Emily M.
Lyles, Robert H.
Manatunga, Amita K.
Danaher, Michelle
Perkins, Neil J.
Schisterman, Enrique F.
TI Regression for Skewed Biomarker Outcomes Subject to Pooling
SO BIOMETRICS
LA English
DT Article
ID LOGNORMAL SUM DISTRIBUTIONS; CARLO EM ALGORITHM; EXPOSURE;
APPROXIMATION; MISCARRIAGE; PREVALENCE; LIKELIHOOD; DESIGN; LIMIT; MODEL
C1 [Mitchell, Emily M.; Lyles, Robert H.; Manatunga, Amita K.] Emory Univ, Rollins Sch Publ Hlth, Dept Biostat & Bioinformat, Atlanta, GA 30322 USA.
[Danaher, Michelle; Perkins, Neil J.; Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Bethesda, MD 20892 USA.
RP Mitchell, EM (reprint author), Emory Univ, Rollins Sch Publ Hlth, Dept Biostat & Bioinformat, Atlanta, GA 30322 USA.
EM emitch8@emory.edu
OI Perkins, Neil/0000-0002-6802-4733; Schisterman,
Enrique/0000-0003-3757-641X
FU National Institute of Nursing Research [1RC4NR012527-01]; National
Institute of Environmental Health Sciences [5R01ES012458-07]; National
Center for Advancing Translational Sciences of the National Institutes
of Health [UL1TR-000454]
FX This research was supported by grants from the National Institute of
Nursing Research (1RC4NR012527-01) and from the National Institute of
Environmental Health Sciences (5R01ES012458-07). Additional partial
support from the National Center for Advancing Translational Sciences of
the National Institutes of Health under Award Number UL1TR-000454 is
also acknowledged. The content is solely the responsibility of the
authors and does not necessarily represent the official views of the
National Institutes of Health.
NR 29
TC 7
Z9 7
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0006-341X
EI 1541-0420
J9 BIOMETRICS
JI Biometrics
PD MAR
PY 2014
VL 70
IS 1
BP 202
EP 211
PG 10
WC Biology; Mathematical & Computational Biology; Statistics & Probability
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
Biology; Mathematics
GA AC4BS
UT WOS:000332466200007
PM 24521420
ER
PT J
AU Hirko, KA
Soliman, AS
Banerjee, M
Ruterbusch, J
Harford, JB
Merajver, SD
Schwartz, K
AF Hirko, Kelly A.
Soliman, Amr S.
Banerjee, Mousumi
Ruterbusch, Julie
Harford, Joe B.
Merajver, Sofia D.
Schwartz, Kendra
TI A Comparison of Criteria to Identify Inflammatory Breast Cancer Cases
from Medical Records and the Surveillance, Epidemiology and End Results
Data base, 2007-2009
SO BREAST JOURNAL
LA English
DT Article
DE diagnostic criteria; inflammatory breast cancer; SEER
ID CARCINOMA INCIDENCE; RESULTS PROGRAM; INSTITUTE; SURVIVAL; FEATURES;
REGISTRY; TUNISIA
AB Inflammatory breast cancer (IBC) is a relatively rare and extremely aggressive form of breast cancer that is diagnosed clinically. Standardization of clinical diagnoses is challenging, both nationally and internationally; moreover, IBC coding definitions used by registries have changed over time. This study aimed to compare diagnostic factors of IBC reported in a U.S. Surveillance, Epidemiology, and End Results (SEER) registry to clinical criteria found in the medical records of all invasive breast cancer cases at a single institution. We conducted a medical record review of all female invasive breast cancers (n=915) seen at an NCI-designated comprehensive cancer center in Detroit from 2007 to 2009. IBC cases were identified based on the presence of the main clinical characteristics of the disease (erythema, edema, peau d'orange). We compared the proportion of IBC out of all breast cancers, using these clinical criteria and the standard SEER IBC codes. In the reviewed cases, the clinical criteria identified significantly more IBC cases (n=74, 8.1%) than the standard IBC SEER definition (n=19, 2.1%; p<0.0001). No IBC cases were identified in the cancer center records using the SEER pathologic coding, which requires the diagnosis of inflammatory carcinoma on the pathology report, a notation that is rarely made. Emphasis must be placed on the documentation of clinical and pathologic characteristics of IBC in the medical record, so that analysis of putative IBC subtypes will be possible. Our results indicate the need for a consensus on the definition of IBC to be utilized in future research.
C1 [Hirko, Kelly A.; Merajver, Sofia D.] Univ Michigan, Dept Epidemiol, Sch Publ Hlth, Ann Arbor, MI 48109 USA.
[Soliman, Amr S.] Univ Nebraska Med Ctr, Coll Publ Hlth, Dept Epidemiol, Omaha, NE USA.
[Banerjee, Mousumi] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.
[Ruterbusch, Julie] Wayne State Univ, Sch Med, Dept Oncol, Detroit, MI USA.
[Harford, Joe B.] NCI, Dept Hlth & Human Serv, Ctr Global Hlth, NIH, Bethesda, MD 20892 USA.
[Merajver, Sofia D.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA.
[Schwartz, Kendra] Wayne State Univ, Sch Med, Dept Family Med & Publ Hlth Sci, Detroit, MI USA.
RP Hirko, KA (reprint author), Univ Michigan, Dept Epidemiol, 109 Observ St, Ann Arbor, MI 48109 USA.
EM kalamb@umich.edu
FU University of Michigan Center for Global Health Predoctoral Fellowship;
Cancer Epidemiology Education in Special Populations Program of the
University of Michigan [CA R25 112383]; Avon Foundation; Breast Cancer
Research Foundation
FX The authors would like to thank Dr. William Anderson and Dr. Catherine
Schairer at the Division of Cancer Epidemiology and Genetics, National
Cancer Institute, for providing expertise on defining IBC from the SEER
data base. We would also like to express gratitude to Kari Borden at the
Detroit SEER registry for providing training on the electronic medical
record system and to Denise Cadwell for her assistance in pulling paper
medical records for this study. Finally, we would like to thank Dr.
Kirsten Herold for her help with editing this manuscript. This research
was supported by the University of Michigan Center for Global Health
Predoctoral Fellowship (K. A. Hirko) and the Cancer Epidemiology
Education in Special Populations Program of the University of Michigan
(CA R25 112383). Additional funding was received from the Avon
Foundation (ASS and SDM) and the Breast Cancer Research Foundation
(SDM).
NR 28
TC 0
Z9 0
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1075-122X
EI 1524-4741
J9 BREAST J
JI Breast J.
PD MAR
PY 2014
VL 20
IS 2
BP 185
EP 191
DI 10.1111/tbj.12234
PG 7
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA AC5ZS
UT WOS:000332600200011
PM 24372839
ER
PT J
AU Louie, GH
Ward, MM
AF Louie, Grant H.
Ward, Michael M.
TI Measurement and treatment of radiographic progression in ankylosing
spondylitis: lessons learned from observational studies and clinical
trials
SO CURRENT OPINION IN RHEUMATOLOGY
LA English
DT Review
DE ankylosing spondylitis; measurement; radiographic progression; treatment
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; RESONANCE-IMAGING EXAMINATIONS;
SACROILIAC JOINT INFLAMMATION; SCORING SYSTEM; SPINE; THERAPY;
SYNDESMOPHYTES; ETANERCEPT; INFLIXIMAB; ADALIMUMAB
AB Purpose of reviewOne of the major goals of treatment of ankylosing spondylitis is to prevent or slow the development of spinal new bone formation. Recent observational studies are compared with the results from clinical trials for the effects of tumor necrosis factor-alpha inhibitors (TNFi) and NSAIDs on radiographic measures of spinal damage.Recent findingsData from clinical trials indicate that treatment up to 2 years with TNFi was not associated with a difference in rates of progression of spinal damage, compared with historical controls. These studies were based on open-label extensions, and analyzed as cohort studies. Recent observational studies have suggested that TNFi may reduce radiographic progression. The different conclusions may be related to the longer treatment and observation period of these observational studies, which may have permitted detection of changes in this slowly evolving process. There is emerging evidence from a clinical trial and retrospective studies that continuous NSAID use may slow radiographic progression.SummaryLack of evidence that TNFi slows radiographic progression in ankylosing spondylitis in data from clinical trials may be because of the design of these studies, and possibly not a true null treatment effect.
C1 [Louie, Grant H.] Johns Hopkins Univ, Sch Med, Div Rheumatol, Baltimore, MD USA.
[Ward, Michael M.] NIAMSD, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Ward, MM (reprint author), NIAMS NIH, Bldg 10 CRC,Room 4-1339,10 Ctr Dr, Bethesda, MD 20892 USA.
EM wardm1@mail.nih.gov
FU Intramural Research Program, National Institute of Arthritis and
Musculoskeletal and Skin Diseases, National Institutes of Health
FX Disclosures: GHL: AbbVie (advisory board); MMW: none. This work was
supported in part by the Intramural Research Program, National Institute
of Arthritis and Musculoskeletal and Skin Diseases, National Institutes
of Health.
NR 29
TC 3
Z9 3
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1040-8711
EI 1531-6963
J9 CURR OPIN RHEUMATOL
JI Curr. Opin. Rheumatol.
PD MAR
PY 2014
VL 26
IS 2
BP 145
EP 150
DI 10.1097/BOR.0000000000000025
PG 6
WC Rheumatology
SC Rheumatology
GA AC9BU
UT WOS:000332829900007
PM 24389865
ER
PT J
AU Dorner, T
Lipsky, PE
AF Doerner, Thomas
Lipsky, Peter E.
TI B cells: depletion or functional modulation in rheumatic diseases
SO CURRENT OPINION IN RHEUMATOLOGY
LA English
DT Review
DE B cells; belimumab; biological therapy; CD20; CD22; rituximab
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; TUMOR-NECROSIS-FACTOR; HELPER T-CELLS;
PERIPHERAL-BLOOD; GERMINAL-CENTERS; PLASMA-CELLS; INADEQUATE RESPONSE;
REGISTRY GRAID; CUTTING EDGE; MURINE LUPUS
AB Purpose of reviewThe availability of drugs directly and indirectly targeting the B cells has refocussed attention on the role of B lymphocytes in rheumatic autoimmune/inflammatory diseases (RAIDs), but their distinct therapeutic potential for certain diseases remains to be further assessed.Recent findingsAlthough additional drugs are currently in clinical development targeting surface molecules (CD19, CD20, CD22, etc.) and cytokines (IL-6, IL-21, BAFF and APRIL) with key effects on B cell/plasma cell survival and differentiation, respectively, recent studies have also provided further insights into the effects of currently available drugs on protective immunity and mechanisms of the initiation and progression of RAIDs (i.e. rituximab, belimumab, mycophenolate and azathioprine). A key aspect of B-cell-directed drugs is their impact on continuous immune activation and chronic maintenance which may differ between individual RAIDs.SummaryThe translational advances in the area of B-cell-depleting therapies and more sophisticated approaches to modulate key B-cell functions, such as blocking B-cell receptor downstream effects, interfering with the differentiation and survival of antigen-experienced memory B and plasma cells are of central interest. Differences in the efficacy and safety profiles of B-cell depletion compared with B-cell-modulating therapies (including antigen-specific tolerance induction) need to be further delineated.
C1 [Doerner, Thomas] Charite, Dept Rheumatol & Clin Immunol, Dept Med CC12, Deutsch Rheuma Forschungszentrum Berlin, D-10117 Berlin, Germany.
[Lipsky, Peter E.] NIAMS, NIH, Bethesda, MD USA.
RP Dorner, T (reprint author), Charite, Dept Med Rheumatol & Clin Immunol Berlin, Charitepl 1, D-10117 Berlin, Germany.
EM thomas.doerner@charite.de
FU DFG [Do491/7-2, Do491/7-3, Do491/5-4]; SFB programs [633/A14, 650/TP14];
Immunobone SPP; Roche/Chugai; Sanofi; Eli Lilly; NovoNordisk; UCB Pharma
FX T.D. received grant support by DFG grants Do491/7-2 and 7-3, 5-4, SFB
programs 633/A14 and 650/TP14 as well as the Immunobone SPP. T. D.
received study support and honoraria for consultancy by Roche/Chugai,
Sanofi, Eli Lilly, NovoNordisk and UCB Pharma.
NR 61
TC 12
Z9 12
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-8711
EI 1531-6963
J9 CURR OPIN RHEUMATOL
JI Curr. Opin. Rheumatol.
PD MAR
PY 2014
VL 26
IS 2
BP 228
EP 236
DI 10.1097/BOR.0000000000000000
PG 9
WC Rheumatology
SC Rheumatology
GA AC9BU
UT WOS:000332829900014
PM 24126901
ER
PT J
AU Gadina, M
AF Gadina, Massimo
TI Advances in kinase inhibition: treating rheumatic diseases and beyond
SO CURRENT OPINION IN RHEUMATOLOGY
LA English
DT Review
DE cytokines; jak; kinase; therapy
ID STAT1 TRANSACTIVATION DOMAIN; TYROSINE KINASE; SERINE PHOSPHORYLATION;
SELECTIVE INHIBITOR; IMMUNE-RESPONSES; IN-VIVO; AUTOIMMUNE; MICE;
ARTHRITIS; JAK3
AB Purpose of reviewKinases inhibitors are now used for the treatment of autoimmune diseases. Here, the most recent findings related to their mechanism of action and some of the newest molecules and targets which are being investigated for autoimmune and inflammatory disorders are reviewed.Recent findingsSimilarly to p38 inhibitors, current spleen tyrosine kinase inhibitors have not fulfilled the expectations of researchers and clinicians, and will likely not be used therapeutically in autoimmunity. Bruton's tyrosine kinase inhibitors remain in the preclinical phase. Studies on the mechanism of action of successful Janus kinase (Jak) inhibitors have revealed that, apart from T and B cells, bone cells such as osteoclasts and innate immunity cells such as dendritic cells are positively affected. More specific, novel Jak inhibitors are now in clinical trials and newer Jak inhibitors are being developed. Other kinases are emerging from basic studies as potentially druggable and will surely be investigated.SummaryFirst-generation pan-Jak inhibitors can be useful for a wide variety of diseases. They act on adaptive as well as innate immune cells and can promote tolerance. More specific inhibitors will soon be available and these may be used in a disease-specific manner.
C1 NIAMSD, Off Sci & Technol, NIH, Bethesda, MD 20892 USA.
RP Gadina, M (reprint author), NIAMSD, Off Sci & Technol, NIH, Bldg 10,Room 10C101-C, Bethesda, MD 20892 USA.
EM gadinama@mail.nih.gov
FU NIAMS Intramural Research Program; Pfizer
FX The work was supported by the by the NIAMS Intramural Research Program.;
The US National Institutes of Health holds a patent related to Janus
family kinases and identification of immune modulators, and has a
Collaborative Research Agreement and Development Award with Pfizer.
NR 47
TC 2
Z9 2
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-8711
EI 1531-6963
J9 CURR OPIN RHEUMATOL
JI Curr. Opin. Rheumatol.
PD MAR
PY 2014
VL 26
IS 2
BP 237
EP 243
DI 10.1097/BOR.0000000000000023
PG 7
WC Rheumatology
SC Rheumatology
GA AC9BU
UT WOS:000332829900016
PM 24419749
ER
PT J
AU Chowdhuri, SR
Fetsch, P
Squires, J
Kohn, E
Filie, AC
AF Chowdhuri, Sinchita Roy
Fetsch, Patricia
Squires, Jennifer
Kohn, Elise
Filie, Armando C.
TI Adenocarcinoma cells in effusion cytology as a diagnostic pitfall with
potential impact on clinical management: A case report with brief review
of immunomarkers
SO DIAGNOSTIC CYTOPATHOLOGY
LA English
DT Review
DE effusion; immunostaining; cytology; reactive mesothelial cells;
adenocarcinoma cells
ID REACTIVE MESOTHELIAL CELLS; CARCINOEMBRYONIC ANTIGEN CEA; EPITHELIAL
OVARIAN-CARCINOMA; SEROUS EFFUSIONS; MALIGNANT MESOTHELIOMA;
MONOCLONAL-ANTIBODIES; IMMUNOHISTOCHEMICAL DIAGNOSIS; METASTATIC
ADENOCARCINOMA; PERITONEAL MESOTHELIOMAS; DIFFERENTIAL-DIAGNOSIS
AB Distinguishing metastatic carcinoma cells from reactive mesothelial cells in effusion samples is often challenging based on morphology alone. Metastatic carcinoma cells in fluid samples may mimic reactive mesothelial cells due to overlapping cytological features. We report a case of a pleural effusion in a 51-year-old female patient with a medical history significant for bilateral ovarian tumors and peritoneal implants diagnosed as serous tumor of borderline malignant potential. The effusion was composed almost entirely of adenocarcinoma cells that morphologically mimicked reactive mesothelial cells. The diagnosis of metastatic adenocarcinoma was made after a wide immunostaining panel of antibodies. Recognizing metastatic adenocarcinoma cells in effusion samples can be challenging and an accurate diagnosis may have significant impact on clinical management as demonstrated by this case. Diagn. Cytopathol. 2012;42:253-258. (c) 2012 Wiley Periodicals, Inc.
C1 [Chowdhuri, Sinchita Roy; Fetsch, Patricia; Filie, Armando C.] NCI, Cytopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Squires, Jennifer; Kohn, Elise] NCI, Mol Signaling Sect, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Filie, AC (reprint author), NCI, Cytopathol Sect, Pathol Lab, Ctr Canc Res, 10 Ctr Dr,Bldg 10,Room 2A19, Bethesda, MD 20892 USA.
EM afilie@mail.nih.gov
FU Intramural Research Program of the NIH (in part), National Cancer
Institute
FX Contract grant sponsor: Intramural Research Program of the NIH (in
part), National Cancer Institute.
NR 57
TC 2
Z9 2
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 8755-1039
EI 1097-0339
J9 DIAGN CYTOPATHOL
JI Diagn. Cytopathol.
PD MAR
PY 2014
VL 42
IS 3
BP 253
EP 258
DI 10.1002/dc.22915
PG 6
WC Medical Laboratory Technology; Pathology
SC Medical Laboratory Technology; Pathology
GA AD8QN
UT WOS:000333530800012
PM 23161830
ER
PT J
AU Losada, L
Pakala, SB
Fedorova, ND
Joardar, V
Shabalina, SA
Hostetler, J
Pakala, SM
Zafar, N
Thomas, E
Rodriguez-Carres, M
Dean, R
Vilgalys, R
Nierman, WC
Cubeta, MA
AF Losada, Liliana
Pakala, Suman B.
Fedorova, Natalie D.
Joardar, Vinita
Shabalina, Svetlana A.
Hostetler, Jessica
Pakala, Suchitra M.
Zafar, Nikhat
Thomas, Elizabeth
Rodriguez-Carres, Marianela
Dean, Ralph
Vilgalys, Rytas
Nierman, William C.
Cubeta, Marc A.
TI Mobile elements and mitochondrial genome expansion in the soil fungus
and potato pathogen Rhizoctonia solani AG-3
SO FEMS MICROBIOLOGY LETTERS
LA English
DT Article
DE Basidiomycota; homing endonucleases; repetitive elements
ID DOUBLE-STRANDED-RNA; NATURAL-POPULATION; AGARICUS-BISPORUS; GROUP-I;
SEQUENCE; DNA; INHERITANCE; EVOLUTION; RECOMBINATION; INTRONS
AB The soil fungus Rhizoctonia solani is an economically important pathogen of agricultural and forestry crops. Here, we present the complete sequence and analysis of the mitochondrial genome of R.solani, field isolate Rhs1AP. The genome (235849bp) is the largest mitochondrial genome of a filamentous fungus sequenced to date and exhibits a rich accumulation of introns, novel repeat sequences, homing endonuclease genes, and hypothetical genes. Stable secondary structures exhibited by repeat sequences suggest that they comprise functional, possibly catalytic RNA elements. RNA-Seq expression profiling confirmed that the majority of homing endonuclease genes and hypothetical genes are transcriptionally active. Comparative analysis suggests that the mitochondrial genome of R.solani is an example of a dynamic history of expansion in filamentous fungi.
C1 [Losada, Liliana; Pakala, Suman B.; Fedorova, Natalie D.; Joardar, Vinita; Hostetler, Jessica; Pakala, Suchitra M.; Zafar, Nikhat; Nierman, William C.] J Craig Venter Inst, Rockville, MD USA.
[Fedorova, Natalie D.; Shabalina, Svetlana A.; Hostetler, Jessica] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
[Thomas, Elizabeth; Rodriguez-Carres, Marianela; Dean, Ralph; Cubeta, Marc A.] N Carolina State Univ, Raleigh, NC 27606 USA.
[Vilgalys, Rytas] Duke Univ, Durham, NC USA.
RP Cubeta, MA (reprint author), N Carolina State Univ, Dept Plant Pathol, 851 Main Campus Dr, Raleigh, NC 27606 USA.
EM macubeta@ncsu.edu
RI Abrams, Natalie/F-4845-2011;
OI Abrams, Natalie/0000-0001-9698-2819; Vilgalys, Rytas/0000-0001-8299-3605
FU NSF/USDA-CSREES Microbial Genome Sequencing Program [2007-35600-18550]
FX We thank Dana Busam, Karen Beeson, Sana Scherbakova, and Lakshmi
Viswanathan from JCVI for assistance with sample processing, library
construction, and sequencing. We are also grateful to Paul Paukstelis
from the University of Maryland for helpful suggestions regarding the
analysis of the RSOL-mtRPT secondary structure. We thank JoAnne Crouch,
Frank Martin, and Stellos Tavantizis for presubmission review of this
manuscript. Funding for this study has been provided by a grant from
NSF/USDA-CSREES Microbial Genome Sequencing Program #2007-35600-18550 to
W.N., R.D., and M.C.
NR 59
TC 11
Z9 11
U1 2
U2 20
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0378-1097
EI 1574-6968
J9 FEMS MICROBIOL LETT
JI FEMS Microbiol. Lett.
PD MAR
PY 2014
VL 352
IS 2
BP 165
EP 173
DI 10.1111/1574-6968.12387
PG 9
WC Microbiology
SC Microbiology
GA AD5UA
UT WOS:000333317500005
PM 24461055
ER
PT J
AU Kumar, N
Gaur, D
Masison, DC
Sharma, D
AF Kumar, Navinder
Gaur, Deepika
Masison, Daniel C.
Sharma, Deepak
TI The BAG Homology Domain of Snl1 Cures Yeast Prion [URE3] Through
Regulation of Hsp70 Chaperones
SO G3-GENES GENOMES GENETICS
LA English
DT Article
DE Snl1; Hsp70; yeast prion; nucleotide exchange factor; BAG domain
ID NUCLEOTIDE EXCHANGE FACTORS; BETA-SHEET STRUCTURE; HEAT-SHOCK-PROTEIN;
SACCHAROMYCES-CEREVISIAE; CELL-SURVIVAL; PROPAGATION; HSP104; STRESS;
HSC70; SUBFAMILY
AB The BAG family of proteins is evolutionarily conserved from yeast to humans and plants. In animals and plants, the BAG family possesses multiple members with overlapping and distinct functions that regulate many cellular processes, such as signaling, protein degradation, and stress response. The only BAG domain protein in Saccharomyces cerevisiae is Snl1, which is anchored to the endoplasmic reticulum through an amino-terminal transmembrane region. Snl1 is the only known membrane-associated nucleotide exchange factor for 70-kilodalton heat shock protein (Hsp70), and thus its role in regulating cytosolic Hsp70 functions is not clear. Here, we examine whether Snl1 regulates Hsp70 activity in the propagation of stable prion-like protein aggregates. We show that unlike other nucleotide exchange factors, Snl1 is not required for propagation of yeast prions [URE3] and [PSI+]. Overexpressing Snl1 derivative consisting of only the BAG domain (Snl1-S) cures [URE3]; however, elevated levels of the entire cytosolic domain of Snl1 (Snl1-M), which has nine additional amino-terminal residues, has no effect. Substituting the three lysine residues in this region of Snl1-M with alanine restores ability to cure [URE3]. [PSI+] is unaffected by overproduction of either Snl1-S or Snl1-M. The Snl1-S mutant engineered with weaker affinity to Hsp70 does not cure [URE3], indicating that curing of [URE3] by Snl1-S requires Hsp70. Our data suggest that Snl1 anchoring to endoplasmic reticulum or nuclear membrane restricts its ability to modulate cytosolic activities of Hsp70 proteins. Furthermore, the short amino-terminal extension of the BAG domain profoundly affects its function.
C1 [Kumar, Navinder; Gaur, Deepika; Sharma, Deepak] Inst Microbial Technol, Council Sci & Ind Res, Chandigarh, India.
[Masison, Daniel C.] Natl Inst Diabet & Digest & Kidney Dis, Lab Biochem & Genet, Bethesda, MD USA.
RP Sharma, D (reprint author), Inst Microbial Technol, Sect 39A, Chandigarh, India.
EM deepaks@imtech.res.in
FU Council of Scientific and Industrial Research (CSIR), India;
Ramalingaswami Re-entry Fellowship, Department of Biotechnology (DBT),
India
FX We thank Dr. Susan R. Wente for providing us strain SWY027 and plasmids
pSW171 and pSW534. The work is supported by Council of Scientific and
Industrial Research (CSIR), India, and the Ramalingaswami Re-entry
Fellowship, Department of Biotechnology (DBT), India.
NR 43
TC 5
Z9 5
U1 0
U2 3
PU GENETICS SOC AM
PI BETHESDA
PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA
SN 2160-1836
J9 G3-GENES GENOM GENET
JI G3-Genes Genomes Genet.
PD MAR
PY 2014
VL 4
IS 3
BP 461
EP 470
DI 10.1534/g3.113.009993
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA AG9PM
UT WOS:000335751700008
PM 24408033
ER
PT J
AU Brielmaier, J
Senerth, JM
Silverman, JL
Matteson, PG
Millonig, JH
DiCicco-Bloom, E
Crawley, JN
AF Brielmaier, J.
Senerth, J. M.
Silverman, J. L.
Matteson, P. G.
Millonig, J. H.
DiCicco-Bloom, E.
Crawley, J. N.
TI Chronic desipramine treatment rescues depression-related, social and
cognitive deficits in Engrailed-2 knockout mice
SO GENES BRAIN AND BEHAVIOR
LA English
DT Article
DE Autism; depression; desipramine; knockout mouse; norepinephrine; social
behavior
ID OBJECT RECOGNITION MEMORY; AUTISM SPECTRUM DISORDER; TAIL SUSPENSION
TEST; ANTIDEPRESSANT TREATMENTS; HIPPOCAMPAL NEUROGENESIS; CHRONIC
FLUOXETINE; CELL LOSS; CEREBELLAR; NOREPINEPHRINE; MOUSE
AB Engrailed-2 (En2) is a homeobox transcription factor that regulates neurodevelopmental processes including neuronal connectivity and elaboration of monoaminergic neurons in the ventral hindbrain. We previously reported abnormalities in brain noradrenergic concentrations in En2 null mutant mice that were accompanied by increased immobility in the forced swim test, relevant to depression. An EN2 genetic polymorphism has been associated with autism spectrum disorders, and mice with a deletion in En2 display social abnormalities and cognitive deficits that may be relevant to multiple neuropsychiatric conditions. This study evaluated the ability of chronic treatment with desipramine (DMI), a selective norepinephrine (NE) reuptake inhibitor and classical antidepressant, to reverse behavioral abnormalities in En2-/- mice. Desipramine treatment significantly reduced immobility in the tail suspension and forced swim tests, restored sociability in the three-chambered social approach task and reversed impairments in contextual fear conditioning in En2-/- mice. Our findings indicate that modulation of brain noradrenergic systems rescues the depression-related phenotype in En2-/- mice and suggest new roles for NE in the pathophysiology of the social and cognitive deficits seen in neuropsychiatric disorders such as autism or schizophrenia.
C1 [Brielmaier, J.; Senerth, J. M.; Silverman, J. L.; Crawley, J. N.] NIMH, Lab Behav Neurosci, Bethesda, MD 20892 USA.
[Matteson, P. G.; Millonig, J. H.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Ctr Adv Biotechnol & Med, New Brunswick, NJ USA.
[Millonig, J. H.; DiCicco-Bloom, E.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurosci & Cell Biol, New Brunswick, NJ USA.
[DiCicco-Bloom, E.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Pediat, New Brunswick, NJ USA.
RP Brielmaier, J (reprint author), George Mason Univ, Dept Psychol, MS 3F5,4400 Univ Dr, Fairfax, VA 22030 USA.
EM jbrielma@gmu.edu
FU National Institute of Mental Health Intramural Research Program; NIH
[R01 MH076624]; NJ Governor's Council for Medical Research and Treatment
of Autism
FX This research was supported by the National Institute of Mental Health
Intramural Research Program (J.B., J.L.S., J.M.S. and J.N.C.), NIH R01
MH076624 (J.H.M. and E.D.B.) and the NJ Governor's Council for Medical
Research and Treatment of Autism (E.D.B.). The authors declare no
conflicts of interest.
NR 45
TC 12
Z9 12
U1 2
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1601-1848
EI 1601-183X
J9 GENES BRAIN BEHAV
JI Genes Brain Behav.
PD MAR
PY 2014
VL 13
IS 3
BP 286
EP 298
DI 10.1111/gbb.12115
PG 13
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA AB8ND
UT WOS:000332046400004
PM 24730055
ER
PT J
AU Pike, ER
Rothenberg, KH
Berkman, BE
AF Pike, Elizabeth R.
Rothenberg, Karen H.
Berkman, Benjamin E.
TI Finding Fault? Exploring Legal Duties to Return Incidental Findings in
Genomic Research
SO GEORGETOWN LAW JOURNAL
LA English
DT Article
ID RESEARCH PARTICIPANTS; CARE RESPONSIBILITIES; MEDICAL RESEARCHERS;
CLINICAL CARE; RECOMMENDATIONS; FUTURE; DISCLOSURE; AUTONOMY; OWE
AB The use of whole-genome sequencing in biomedical research is expected to produce dramatic advances in human health. The increasing use of this powerful, data-rich new technology in research, however; will inevitably give rise to incidental findings (IFs)-findings with individual health or reproductive significance that are beyond the aims of the particular research-and the related questions of whether and to what extent researchers have an ethical obligation to return IFs. Many have concluded that researchers have an ethical obligation to return some findings in some circumstances but have provided vague or context-dependent approaches to determining which IFs must be returned and when. As a result, researchers have started returning IFs inconsistently, giving rise to concerns about legal liability in circumstances in which notification could have potentially prevented injury. Although it is clear that ethical guidance should not be automatically codified as law and that crafting ethical obligations around legal duties can be inappropriate, the ethical debate should not proceed unaware of the potential legal ramifications of advancing and implementing an ethical obligation to return IFs.
This Article assesses the legal claims that could be brought for a researcher's failure to return IFs. The potential for researchers to be held liable in tort is still uncertain and turns largely on a number of factors-including customary practice and guidance documents-that are still in flux. Unlike medical care, which has a well-defined duty into which evolving scientific knowledge about genetics and genomics can readily be incorporated, a researcher's duty to return IFs is less well defined, making it difficult to determine at the outset whether and when legal liability will attach.
This Article advocates for a clearer; ethically sound standard of requiring that researchers disclose in the informed consent document which approach to offering IFs will be taken. This approach enables participants to know at the outset which findings, if any, will be returned, allows researchers to ascertain when their failure to appropriately return incidental findings will give rise to liability, and enables courts to make determinations that will produce more consistent legal guidance.
C1 [Pike, Elizabeth R.] Natl Inst Hlth, Dept Bioeth, Bethesda, MD USA.
[Rothenberg, Karen H.] Univ Maryland, Sch Law, Law & Hlth Care Program, College Pk, MD 20742 USA.
[Rothenberg, Karen H.] Natl Human Genome Res Inst, Bethesda, MD USA.
[Berkman, Benjamin E.] Natl Human Genome Res Inst, Bioeth Core, Bethesda, MD USA.
FU Intramural NIH HHS [Z99 HG999999]
NR 95
TC 8
Z9 8
U1 0
U2 4
PU GEORGETOWN LAW JOURNAL ASSOC
PI WASHINGTON
PA 600 NEW JERSEY AVE N W, WASHINGTON, DC 20001 USA
SN 0016-8092
J9 GEORGETOWN LAW J
JI Georget. Law J.
PD MAR
PY 2014
VL 102
IS 3
BP 795
EP 843
PG 49
WC Law
SC Government & Law
GA AH2FY
UT WOS:000335938100004
PM 25346543
ER
PT J
AU Marks, KM
Kitch, D
Chung, RT
Hadigan, C
Andersen, J
Tien, P
Luetkemeyer, A
Alston-Smith, B
Glesby, MJ
AF Marks, Kristen M.
Kitch, Douglas
Chung, Raymond T.
Hadigan, Colleen
Andersen, Janet
Tien, Phyllis
Luetkemeyer, Annie
Alston-Smith, Beverly
Glesby, Marshall J.
CA A5239 Team
TI Pilot Study of Pioglitazone Before HCV Retreatment in HIV/HCV Genotype
1-Infected Subjects With Insulin Resistance and Previous Nonresponse to
Peginterferon and Ribavirin Therapy: A5239
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE metabolic; hepatitis C; nonresponder; pegylated interferon; insulin
resistance; HIV
ID HEPATITIS-C VIRUS; ALPHA-2A PLUS RIBAVIRIN; VIROLOGICAL RESPONSE;
COINFECTED PATIENTS; NONALCOHOLIC STEATOHEPATITIS; ANTIRETROVIRAL
THERAPY; INFECTED PATIENTS; HIV; STEATOSIS; METFORMIN
AB Insulin resistance is associated with nonresponse to hepatitis C virus (HCV) treatment. In this multicenter, single-arm pilot study, adult, HIV/HCV genotype 1-coinfected previous nonresponders to peginterferon/ribavirin (PegIFN/RBV) with homeostatic model assessment of insulin resistance >2.5 were treated with pioglitazone (PIO) for 24 weeks followed by PegIFN/RBV/PIO. Three of 19 subjects (15.8%) achieved undetectable HCV RNA at week 24 of PegIFN/RBV/PIO, which was not significantly different than the historical null rate of 10% (P = 0.29, lower limit of the exact 1-sided 90% confidence interval 5.9%). Over the 24 weeks of PIO monotherapy, alanine aminotransferase and aspartate aminotransferase declined significantly and correlated with improved metabolic parameters.
C1 [Marks, Kristen M.; Glesby, Marshall J.] Weill Cornell Med Coll, Div Infect Dis, New York, NY 10065 USA.
[Kitch, Douglas; Andersen, Janet] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Div, Boston, MA USA.
[Hadigan, Colleen; Alston-Smith, Beverly] NIAID, NIH, Bethesda, MD 20892 USA.
[Tien, Phyllis] Univ Calif San Francisco, Sch Med, Div Infect Dis, San Francisco, CA USA.
[Tien, Phyllis] Dept Vet Affairs, Med Serv, San Francisco, CA USA.
[Luetkemeyer, Annie] Univ Calif San Francisco, San Francisco Gen Hosp, Div HIV AIDS, San Francisco, CA USA.
RP Marks, KM (reprint author), Weill Cornell Med Coll, Div Infect Dis, 525 East 68th St,F24, New York, NY 10065 USA.
EM markskr@med.cornell.edu
FU National Institute of Allergy and Infectious Diseases [UM1AI068636];
National Institute of Mental Health, National Institute of Dental and
Craniofacial Research; Roche (Genentech); Takeda Pharmaceuticals, USA,
Inc.; AACTG/ACTG Statistical and Data Management Center [1 UM1 AI068634,
5 U01 AI38855]; Intramural National Institute of Allergy and Infectious
Diseases support [NIH DK078772, K24 AI078884, U01 AI069502]; Roche
Laboratories; Bristol-Myers Squibb; Gilead; Vertex Pharmaceuticals;
Pfizer; Gilead Sciences; SIGA Technologies; Boehringer Ingelheim; CTU
[U01 AI69419, 5UO1 AI069502-07, UM1AI069532, UM1 AI069511, AI69501, AI
069471, UM1-AI069503, IU0IAI69472]; CTSCs from the National Center for
Advancing Translational Sciences component of the National Institutes of
Health (NIH) [UL1 TR000457, UL1TR000439]; National Center for Advancing
Translational Sciences (Virginia Commonwealth University) [UL1TR000058]
FX Supported by Award Number UM1AI068636 from the National Institute of
Allergy and Infectious Diseases and supported by National Institute of
Mental Health, National Institute of Dental and Craniofacial Research.
This research was also supported by Roche (Genentech) and Takeda
Pharmaceuticals, USA, Inc. Other grant support included 1 UM1 AI068634
and 5 U01 AI38855 to AACTG/ACTG Statistical and Data Management Center;
Intramural National Institute of Allergy and Infectious Diseases support
(C. H.); NIH DK078772 (R. T. C.); K24 AI078884 (M. G.), U01 AI069502 (A.
L.). R. T. C. received research funding from Roche Laboratories. A. L.
has received research grant support to University of California San
Francisco from Bristol-Myers Squibb, Gilead, and Vertex Pharmaceuticals.
M.J.G. has received research support from Pfizer to Weill Cornell
Medical College and has served as a consultant to Gilead Sciences, SIGA
Technologies, and Pfizer. K. M. M. has received research support to
Weill Cornell Medical College from Bristol-Myers Squibb, Vertex
Pharmaceuticals, Janssen Pharmaceuticals, Boehringer Ingelheim, and
Gilead and has received honoraria for lectures from Boehringer Ingelheim
and Bristol-Myers Squibb. Also supported in part by CTU grants,
including U01 AI69419 [Cornell (Site 7804)], 5UO1 AI069502-07
[University of California San Francisco AIDS CRS (Site 801)],
UM1AI069532 [New York University/NYC HHC at Bellevue Hospital Center
(Site 401)], UM1 AI069511 [University of Rochester (Site 1101)], AI69501
[MetroHealth Medical Center (Site 2503)], AI 069471 [Northwestern
University (A2701)], UM1-AI069503 [Virginia Commonwealth University
(Site 31475)], and Massachusetts General Hospital (Site 101) CTU Grant
IU0IAI69472. Also supported in part by grants funded by site CTSCs,
including UL1 TR000457 (Cornell CTSC), UL1TR000439 from the National
Center for Advancing Translational Sciences component of the National
Institutes of Health (NIH) and NIH roadmap for Medical Research
(Clinical and Translational Science Collaborative of Cleveland),
UL1TR000058 from the National Center for Advancing Translational
Sciences (Virginia Commonwealth University).
NR 19
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD MAR 1
PY 2014
VL 65
IS 3
BP 345
EP 349
DI 10.1097/QAI.0000000000000073
PG 5
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA AH0DL
UT WOS:000335789200025
PM 24525470
ER
PT J
AU Fowler, MG
Coovadia, H
Herron, CM
Maldonado, Y
Chipato, T
Moodley, D
Musoke, P
Aizire, J
Manji, K
Stranix-Chibanda, L
Fawzi, W
Chetty, V
Msweli, L
Kisenge, R
Brown, E
Mwatha, A
Eshleman, SH
Richardson, P
Allen, M
George, K
Andrew, P
Zwerski, S
Mofenson, LM
Jackson, JB
AF Fowler, Mary Glenn
Coovadia, Hoosen
Herron, Casey M.
Maldonado, Yvonne
Chipato, Tsungai
Moodley, Dhayendre
Musoke, Philippa
Aizire, Jim
Manji, Karim
Stranix-Chibanda, Lynda
Fawzi, Wafaie
Chetty, Vani
Msweli, Lindiwe
Kisenge, Rodrick
Brown, Elizabeth
Mwatha, Anthony
Eshleman, Susan H.
Richardson, Paul
Allen, Melissa
George, Kathleen
Andrew, Philip
Zwerski, Sheryl
Mofenson, Lynne M.
Jackson, J. Brooks
CA HPTN 046 Protocol Team
TI Efficacy and Safety of an Extended Nevirapine Regimen in Infants of
Breastfeeding Mothers With HIV-1 Infection for Prevention of HIV-1
Transmission (HPTN 046): 18-Month Results of a Randomized, Double-Blind,
Placebo-Controlled Trial
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE PMTCT; nevirapine; infant HIV prophylaxis
ID ANTIRETROVIRAL REGIMENS; CHILDREN
AB Background: HPTN 046 compared the efficacy and safety of infant nevirapine (NVP) among HIV-exposed breastfed infants randomized at 6 weeks to 6 months to t NVP or placebo to prevent postnatal infection: we report final 18-month outcomes. Methods: Randomized, placebo-controlled trial in 4 African countries. Infant diagnostic HIV testing was performed regularly from birth through 18 months. Kaplan-Meier analysis was used to assess 18-month cumulative infant HIV infection, HIV infection/or death, and mortality rates. Results: Between 6 weeks and 6 months, postnatal HIV infection rates were significantly lower among infants receiving daily NVP from 6 weeks to 6 months 1.1% [95% confidence interval (CI): 0.2% to 1.8%], compared with placebo 2.4% (95% CI: 1.3% to 2.6%), P = 0.049, but not significantly lower thereafter. Eighteen-month postnatal infection rates were low: 2.2% (95% CI: 1.1% to 3.3%) versus 3.1% (95% CI: 1.9% to 4.4%), respectively, P = 0.28. Mortality and HIV infection/death did not differ between arms at any age. Infants of women receiving antiretroviral therapy (ART) for their own health had the lowest 18-month postnatal infection rates (0.5%, 95% CI: 0.0% to 1.1%). However, HIV infection/death rates at 18 months were not significantly different for infants of mothers on ART (3.7%, 95% CI: 1.9% to 5.5%), and infants of mothers with CD4 counts of >= 350 cells per cubic millimeter not receiving ART (4.8%, 95% CI: 2.7% to 6.8%; P = 0.46). There were no differences in adverse events between study arms. Conclusions: This trial demonstrated early but not late differences in postnatal HIV transmission among infants randomized at age 6 weeks to extended NVP or placebo, underscoring the importance of continued prophylaxis throughout breastfeeding.
C1 [Fowler, Mary Glenn; Eshleman, Susan H.; Richardson, Paul; Jackson, J. Brooks] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Coovadia, Hoosen] Univ Witwatersrand, ZA-2050 Johannesburg, South Africa.
[Herron, Casey M.; Brown, Elizabeth; Mwatha, Anthony] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Maldonado, Yvonne] Stanford Univ, Dept Pediat, Sch Med, Stanford, CA 94305 USA.
[Chipato, Tsungai] Univ Zimbabwe, Dept Obstet & Gynecol, Coll Hlth Sci, Harare, Zimbabwe.
[Moodley, Dhayendre; Chetty, Vani; Msweli, Lindiwe] Univ KwaZulu Natal, Ctr AIDS Programme Res South Africa CAPRISA, Nelson R Mandela Sch Med, Durban, South Africa.
[Musoke, Philippa; Aizire, Jim; Allen, Melissa] Johns Hopkins Univ, Makerere Univ, Res Collaborat, Kampala, Uganda.
[Manji, Karim; Kisenge, Rodrick] Muhimbili Univ Hlth & Allied Sci, Dar Es Salaam, Tanzania.
[Stranix-Chibanda, Lynda] Univ Zimbabwe, Dept Pediat, Coll Hlth Sci, Harare, Zimbabwe.
[Fawzi, Wafaie; George, Kathleen] Harvard Univ, Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA 02115 USA.
[Andrew, Philip] Family Hlth Int, Res Triangle Pk, NC 27709 USA.
[Zwerski, Sheryl] NIAID, Div HIV AIDS, US Natl Inst Hlth, Bethesda, MD 20892 USA.
[Mofenson, Lynne M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal & Pediat Infect Dis Branch, NIH, Rockville, MD USA.
RP Fowler, MG (reprint author), Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
EM mgfowler@mujhu.org
OI Mofenson, Lynne/0000-0002-2818-9808
FU National Institutes of Health (National Institute of Allergy and
Infectious Diseases) [U01 AI068632]; National Institutes of Health
(Eunice Kennedy Shriver National Institute of Child Health and Human
Development) [U01 AI068632]; US National Institutes of Health through
the HPTN; US National Institutes of Health through International
Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) group;
National Institute of Allergy and Infectious Diseases (NIAID); Eunice
Kennedy Shriver National Institute of Child Health and Human Development
(NICHD); National Institute of Drug Abuse; National Institute of Mental
Health (NIMH); NIAID [U01AI068632]; NICHD; NIMH; Boehringer Ingelheim
Pharmaceuticals
FX Supported by the National Institutes of Health (National Institute of
Allergy and Infectious Diseases, and Eunice Kennedy Shriver National
Institute of Child Health and Human Development) Grant U01 AI068632. HIV
Prevention Trials Network (HPTN) 046 (ClinicalTrials.gov Identifier:
NCT00074412) was funded by the US National Institutes of Health,
initially through the HPTN and later through the International Maternal
Pediatric Adolescent AIDS Clinical Trials (IMPAACT) group. The HPTN
(U01AI46749) has been funded by the National Institute of Allergy and
Infectious Diseases (NIAID), the Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD), National
Institute of Drug Abuse, and National Institute of Mental Health (NIMH).
The IMPAACT Group (U01AI068632) has been funded by NIAID, NICHD, and
NIMH. The study products were provided free of charge by Boehringer
Ingelheim Pharmaceuticals.
NR 22
TC 8
Z9 8
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD MAR 1
PY 2014
VL 65
IS 3
BP 366
EP 374
DI 10.1097/QAI.0000000000000052
PG 9
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA AH0DL
UT WOS:000335789200028
PM 24189151
ER
PT J
AU Spinner, JL
Winfree, S
Starr, T
Shannon, JG
Nair, V
Steele-Mortimer, O
Hinnebusch, BJ
AF Spinner, Justin L.
Winfree, Seth
Starr, Tregei
Shannon, Jeffrey G.
Nair, Vinod
Steele-Mortimer, Olivia
Hinnebusch, B. Joseph
TI Yersinia pestis survival and replication within human neutrophil
phagosomes and uptake of infected neutrophils by macrophages
SO JOURNAL OF LEUKOCYTE BIOLOGY
LA English
DT Article
DE polymorphonuclear leukocytes; phagocytosis; intracellular; apoptosis;
efferocytosis
ID PRIMARY PNEUMONIC PLAGUE; MOUSE PERITONEAL-MACROPHAGES; III SECRETION
SYSTEM; POLYMORPHONUCLEAR LEUKOCYTES; PASTEURELLA-PESTIS; CELL-DEATH;
SPONTANEOUS APOPTOSIS; RECEPTOR ANTAGONIST; LEISHMANIA-MAJOR; LYMPH-NODE
AB Yersinia pestis survives and replicates within PMNs, which are taken up by macrophages in vitro. Yersinia pestis, the bacterial agent of plague, is transmitted by fleas. The bite of an infected flea deposits Y. pestis into the dermis and triggers recruitment of innate immune cells, including phagocytic PMNs. Y. pestis can subvert this PMN response and survive at the flea-bite site, disseminate, and persist in the host. Although its genome encodes a number of antiphagocytic virulence factors, phagocytosis of Y. pestis by PMNs has been observed. This study tests the hypotheses that Y. pestis, grown at the ambient temperature of the flea vector (21 degrees C), where the major antiphagocytic virulence factors are not produced, can survive and replicate within human PMNs and can use PMNs as a route to infect macrophages subsequently. We show that Y. pestis is localized within PMN phagosomes, predominately as individual bacteria, and that intracellular bacteria can survive and replicate. Within 12 h of infection, approximate to 70% of infected PMNs had PS on their surface and were plausibly competent for efferocytosis. With the use of live cell confocal imaging, we show that autologous HMDMs recognize and internalize infected PMNs and that Y. pestis survives and replicates within these HMDMs following efferocytosis. Addition of HMDMs to infected PMNs resulted in decreased secretion of inflammatory cytokines (compared with HMDMs incubated directly with pCD1(-) Y. pestis) and increased secretion of the anti-inflammatory cytokine IL-1ra. Thus, Y. pestis can survive and replicate within PMNs, and infected PMNs may be a route for noninflammatory infection of macrophages.
C1 [Spinner, Justin L.; Shannon, Jeffrey G.; Hinnebusch, B. Joseph] NIAID, Lab Zoonot Pathogens, Res Technol Branch, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA.
[Winfree, Seth; Starr, Tregei; Steele-Mortimer, Olivia] NIAID, Labs Intracellular Parasites, Res Technol Branch, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA.
[Nair, Vinod] NIAID, Electron Microscopy Unit, Res Technol Branch, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA.
RP Spinner, JL (reprint author), NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, 903 South 4th St, Hamilton, MT 59840 USA.
EM justin.spinner@nih.gov
FU Division of Intramural Research, NIAID, U.S. National Institutes of
Health
FX This research was supported by the Division of Intramural Research,
NIAID, U.S. National Institutes of Health. We thank Frank DeLeo, Addie
Porter, Kevin Braughton, and Brett Freedman for providing isolated human
PMNs and blood samples. We thank Yi-Cheng Sun for providing the plasmid
pCD1 Delta yadA::kan. We thank Chris Bosio, Iman Chouikha, Clayton
Jarrett, Aaron Hasenkrug, and Scott Kobayashi for critical review of the
manuscript.
NR 56
TC 9
Z9 9
U1 0
U2 8
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0741-5400
EI 1938-3673
J9 J LEUKOCYTE BIOL
JI J. Leukoc. Biol.
PD MAR
PY 2014
VL 95
IS 3
BP 389
EP 398
DI 10.1189/jlb.1112551
PG 10
WC Cell Biology; Hematology; Immunology
SC Cell Biology; Hematology; Immunology
GA AG3MU
UT WOS:000335324400003
PM 24227798
ER
PT J
AU Siddoway, B
Hou, HL
Yang, HT
Petralia, R
Xia, HH
AF Siddoway, Benjamin
Hou, Hailong
Yang, Hongtian
Petralia, Ronald
Xia, Houhui
TI Synaptic activity bidirectionally regulates a novel sequence-specific
S-Q phosphoproteome in neurons
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE L-type calcium channels; Phosphoproteomics; phosphorylation; SQ motif;
synaptic activity
ID ATM PROTEIN; DNA-DAMAGE; EMBRYONIC LETHALITY; SIGNALING PATHWAYS;
PLASTICITY; KINASES; MICE; PHOSPHORYLATION; ACTIVATION; MEMORY
AB Protein phosphorylation plays a critical role in neuronal transcription, translation, cell viability, and synaptic plasticity. In neurons, phospho-enzymes and specific substrates directly link glutamate release and post-synaptic depolarization to these cellular functions; however, many of these enzymes and their protein substrates remain uncharacterized or unidentified. In this article, we identify a novel, synaptically driven neuronal phosphoproteome characterized by a specific motif of serine/threonine-glutamine ([S/T]-Q, abbreviated as SQ). These SQ-containing substrates are predominantly localized to dendrites, synapses, the soma; and activation of this SQ phosphoproteome by bicuculline application is induced via calcium influx through L-type calcium channels. On the other hand, acute application of NMDA can inactivate this SQ phosphoproteome. We demonstrate that the SQ motif kinase Ataxia-telangiectasia mutated can also localize to dendrites and dendritic spines, in addition to other subcellular compartments, and is activated by bicuculline application. Pharmacology studies indicate that Ataxia-telangiectasia mutated and its sister kinase ataxia telangiectasia mutated and Rad3-related up-regulate these neuronal SQ substrates. Phosphoproteomics identified over 150 SQ-containing substrates whose phosphorylation is bidirectionally regulated by synaptic activity.
C1 [Siddoway, Benjamin; Hou, Hailong; Yang, Hongtian; Xia, Houhui] Louisiana State Univ, Ctr Neurosci, Hlth Sci Ctr, New Orleans, LA 70112 USA.
[Petralia, Ronald] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA.
RP Xia, HH (reprint author), Louisiana State Univ, Ctr Excellence, Hlth Sci Ctr, New Orleans, LA 70112 USA.
EM hxia@lsuhsc.edu
FU NIH [R01NS060879]; NSF [IOS-0824393]; NARSAD [2006YI]; LSU REF (Research
Enhancement Fund); NIDCD Intramural Research Program;
Ataxia-Telangiectasia Children's Project (ATCP)
FX This work is supported by NIH R01NS060879, NSF IOS-0824393, NARSAD
(2006YI), and LSU REF (Research Enhancement Fund) to HX, the NIDCD
Intramural Research Program to RSP, and the Ataxia-Telangiectasia
Children's Project (ATCP) to BS. We thank Dr Ya-Xian Wang for help with
the immunogold study. The authors declare no competing financial
interests.
NR 34
TC 4
Z9 4
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3042
EI 1471-4159
J9 J NEUROCHEM
JI J. Neurochem.
PD MAR
PY 2014
VL 128
IS 6
BP 841
EP 851
DI 10.1111/jnc.12487
PG 11
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA AC2PV
UT WOS:000332347300007
PM 24117848
ER
PT J
AU Hicks, R
Koroshetz, W
AF Hicks, Ramona
Koroshetz, Walter
TI NIH PARTICIPATION IN THE INTERNATIONAL TRAUMATIC BRAIN INJURY RESEARCH
(INTBIR) INITIATIVE
SO JOURNAL OF NEUROTRAUMA
LA English
DT Meeting Abstract
CT 11th Symposium of the International-Neurotrauma-Society
CY MAR 19-23, 2014
CL Budapest, HUNGARY
SP Int Neurotrauma Soc
C1 [Hicks, Ramona; Koroshetz, Walter] NINDS, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
EI 1557-9042
J9 J NEUROTRAUM
JI J. Neurotrauma
PD MAR 1
PY 2014
VL 31
IS 5
MA 204
BP A63
EP A63
PG 1
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA AB4ZV
UT WOS:000331799600205
ER
PT J
AU Forde, PM
Hooker, CM
Boikos, SA
Petrini, I
Giaccone, G
Rudin, CM
Yang, SC
Illei, PB
Hann, CL
Ettinger, DS
Brahmer, JR
Kelly, RJ
AF Forde, Patrick M.
Hooker, Craig M.
Boikos, Sosipatros A.
Petrini, Iacope
Giaccone, Giuseppe
Rudin, Charles M.
Yang, Stephen C.
Illei, Peter B.
Hann, Christine L.
Ettinger, David S.
Brahmer, Julie R.
Kelly, Ronan J.
TI Systemic Therapy, Clinical Outcomes, and Overall Survival in Locally
Advanced or Metastatic Pulmonary Carcinoid
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Article
DE Pulmonary carcinoid; Metastatic carcinoid; Chemotherapy pulmonary
carcinoid; Chemotherapy bronchial carcinoid; Therapy carcinoid; Atypical
carcinoid; Typical carcinoid
ID NEUROENDOCRINE TUMORS; EXPERIENCE; RADIANT-2; PHASE-3
AB Background: Data to guide the management of advanced pulmonary carcinoid (APC) come from retrospective reports and subgroup analyses of trials that included mainly extrapulmonary carcinoid tumors. We report the largest series to date of 49 patients with locally advanced or metastatic pulmonary carcinoid.
Methods: The Johns Hopkins Pathology Database was reviewed for APC patients treated between January 1992 and December 2012. Data on time to recurrence, progression-free survival, and overall survival were estimated by using the Kaplan-Meier method.
Results: Forty-nine patients were treated for APC in the specified time period. Median time to recurrence after surgical resection was 2.5 years (atypical carcinoid [AC] versus typical carcinoid [TC], 2.5 versus 6.3 years; p = 0.063). Median survival with advanced disease was 7.1 years and significantly longer for TC compared with AC (10.2 versus 4 years; p = 0.009). Among the diverse systemic therapies used, responses occurred in four of 17 patients (23.5%) who received platinum/etoposide with a median progression-free survival of 7 months.
Conclusion: Although systemic chemotherapy has moderate activity for APC, novel approaches are required. TC and AC, although both classified as pulmonary carcinoid, are clearly different clinical and molecular entities and require separate treatment paradigms in the advanced/metastatic setting.
C1 [Forde, Patrick M.; Boikos, Sosipatros A.; Rudin, Charles M.; Hann, Christine L.; Ettinger, David S.; Brahmer, Julie R.; Kelly, Ronan J.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Dept Med Oncol, Baltimore, MD USA.
[Hooker, Craig M.; Yang, Stephen C.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Dept Surg, Baltimore, MD USA.
[Illei, Peter B.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Dept Pathol, Baltimore, MD USA.
[Petrini, Iacope; Giaccone, Giuseppe] NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
RP Kelly, RJ (reprint author), Johns Hopkins Univ, Canc Res Bldg 1,1650 Orleans St,Room G93, Baltimore, MD 21287 USA.
EM rkelly25@jhmi.edu
RI Petrini, Iacopo/K-7316-2016; Giaccone, Giuseppe/E-8297-2017
OI Petrini, Iacopo/0000-0002-7752-6866; Giaccone,
Giuseppe/0000-0002-5023-7562
FU NCI NIH HHS [P30 CA006973]
NR 14
TC 5
Z9 5
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1556-0864
EI 1556-1380
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD MAR
PY 2014
VL 9
IS 3
BP 414
EP 418
DI 10.1097/JTO.0000000000000065
PG 5
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA AB1EO
UT WOS:000331534500024
PM 24518093
ER
PT J
AU Modi, MN
Palmer, S
Armstrong, A
AF Modi, Monica N.
Palmer, Sheallah
Armstrong, Alicia
TI The Role of Violence Against Women Act in Addressing Intimate Partner
Violence: A Public Health Issue
SO JOURNAL OF WOMENS HEALTH
LA English
DT Article
ID DOMESTIC VIOLENCE; SUICIDAL-BEHAVIOR; PREVALENCE; CARE; PREGNANCY;
HISTORY
AB Intimate partner violence (IPV) is defined as violence committed by a current or former boyfriend or girlfriend, spouse or ex-spouse. Each year, 1.3 to 5.3 million women in the United States experience IPV. The large number of individuals affected, the enormous healthcare costs, and the need for a multidisciplinary approach make IPV an important healthcare issue. The Violence Against Women Act (VAWA) addresses domestic violence, dating violence, sexual assault, and stalking. It emphasizes development of coordinated community care among law enforcement, prosecutors, victim services, and attorneys. VAWA was not reauthorized in 2012 because it lacked bipartisan support. VAWA 2013 contains much needed new provisions for Native Americans; lesbian, gay, bisexual, transgender, gay, and queer (LGBTQ) individuals; and victims of human trafficking but does not address the large amount of intimate partner violence in America's immigrant population. There are important remaining issues regarding intimate partner violence that need to be addressed by future legislation. This review examines the role of legislation and addresses proposals for helping victims of IPV.
C1 [Modi, Monica N.; Armstrong, Alicia] NICHHD, Program Reprod & Adult Endocrinol, NIH, Rockville, MD 20852 USA.
[Palmer, Sheallah] Florida State Univ, Coll Med, Tallahassee, FL 32306 USA.
RP Armstrong, A (reprint author), NICHHD, NIH, 6100 Execut Blvd, Rockville, MD 20852 USA.
EM armstroa@mail.nih.gov
NR 53
TC 8
Z9 8
U1 8
U2 53
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-9996
EI 1931-843X
J9 J WOMENS HEALTH
JI J. Womens Health
PD MAR 1
PY 2014
VL 23
IS 3
BP 253
EP 259
DI 10.1089/jwh.2013.4387
PG 7
WC Public, Environmental & Occupational Health; Medicine, General &
Internal; Obstetrics & Gynecology; Women's Studies
SC Public, Environmental & Occupational Health; General & Internal
Medicine; Obstetrics & Gynecology; Women's Studies
GA AC4BQ
UT WOS:000332466000011
PM 24299159
ER
PT J
AU Jonsson, E
Salmon, A
Warren, KR
AF Jonsson, Egon
Salmon, Amy
Warren, Kenneth R.
TI The international charter on prevention of fetal alcohol spectrum
disorder
SO LANCET GLOBAL HEALTH
LA English
DT Editorial Material
ID PERSPECTIVE; PREVALENCE
C1 [Jonsson, Egon; Salmon, Amy] Inst Hlth Econ, Edmonton, AB T5J 3N4, Canada.
[Warren, Kenneth R.] NIAAA, NIH, US Dept HHS, Bethesda, MD USA.
RP Jonsson, E (reprint author), Inst Hlth Econ, Edmonton, AB T5J 3N4, Canada.
EM ejonsson@ihe.ca
OI Salmon, Amy/0000-0002-1337-7582
NR 10
TC 14
Z9 14
U1 0
U2 2
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2214-109X
J9 LANCET GLOB HEALTH
JI Lancet Glob. Health
PD MAR
PY 2014
VL 2
IS 3
BP E135
EP E137
DI 10.1016/S2214-109X(13)70173-6
PG 3
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AH8YR
UT WOS:000336424600010
PM 25102841
ER
PT J
AU Sly, PD
Neira, M
Collman, G
Carpenter, DO
Landrigan, PJ
Van Den Berg, M
Barriga, FD
Ruchirawat, M
Laborde, A
Pascale, A
Heacock, M
Dalmau, MT
Suk, WA
AF Sly, Peter D.
Neira, Maria
Collman, Gwen
Carpenter, David O.
Landrigan, Philip J.
Van Den Berg, Martin
Diaz Barriga, Fernando
Ruchirawat, Mathuros
Laborde, Amalia
Pascale, Antonio
Heacock, Michelle
Dalmau, Marguerite T.
Suk, William A.
TI Networking to advance progress in children's environmental health
SO LANCET GLOBAL HEALTH
LA English
DT Editorial Material
ID SYSTEMATIC ANALYSIS; GLOBAL BURDEN; DISEASES
C1 [Sly, Peter D.; Dalmau, Marguerite T.] Univ Queensland, WHO Collaborating Ctr Childrens Hlth & Environm, Childrens Hlth & Environm Program, Brisbane, Qld 4029, Australia.
[Neira, Maria] WHO, Publ Hlth & Environm, CH-1211 Geneva, Switzerland.
[Collman, Gwen; Heacock, Michelle; Suk, William A.] NIEHS, WHO Collaborating Ctr Environm Hlth Sci, Res Triangle Pk, NC 27709 USA.
[Carpenter, David O.] SUNY Albany, WHO Collaborating Ctr Environm Hlth, Inst Hlth & Environm, Albany, NY 12222 USA.
[Landrigan, Philip J.] Mt Sinai Sch Med, WHO Collaborating Ctr Childrens Environm Hlth, New York, NY USA.
[Van Den Berg, Martin] Univ Utrecht, Inst Risk Assessment Sci, WHO Collaborating Ctr Res Environm Hlth Risk Asse, Utrecht, Netherlands.
[Diaz Barriga, Fernando] Univ Autonoma San Luis Potosi, WHO Collaborating Ctr Childrens Environm Hlth & H, San Luis Potosi, Mexico.
[Ruchirawat, Mathuros] Chulabhorn Res Inst, WHO Collaborating Ctr Capac Bldg & Res Environm H, Bangkok, Thailand.
[Laborde, Amalia; Pascale, Antonio] Univ Republ Oriental Uruguay, WHO Collaborating Ctr Human Environm Toxicol, Dept Toxicol, Montevideo, Uruguay.
RP Sly, PD (reprint author), Univ Queensland, WHO Collaborating Ctr Childrens Hlth & Environm, Childrens Hlth & Environm Program, Brisbane, Qld 4029, Australia.
EM p.sly@uq.edu.au
RI Sly, Peter/F-1486-2010
OI Sly, Peter/0000-0001-6305-2201
NR 10
TC 7
Z9 8
U1 1
U2 6
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2214-109X
J9 LANCET GLOB HEALTH
JI Lancet Glob. Health
PD MAR
PY 2014
VL 2
IS 3
BP E129
EP E130
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AH8YR
UT WOS:000336424600007
PM 25102838
ER
PT J
AU Turkbey, B
Kobayashi, H
Hoyt, RF
Choyke, PL
Nakajima, T
Griffiths, GL
Bernardo, M
Rialon, K
Fishman, SJ
Sena, LM
AF Turkbey, Baris
Kobayashi, Hisataka
Hoyt, Robert F., Jr.
Choyke, Peter L.
Nakajima, Takahito
Griffiths, Gary L.
Bernardo, Marcelino
Rialon, Kristy
Fishman, Steven J.
Sena, Laureen M.
TI Magnetic Resonance Lymphography of the Thoracic Duct after Interstitial
Injection of Gadofosveset Trisodium: A Pilot Dosing Study in a Porcine
Model
SO LYMPHATIC RESEARCH AND BIOLOGY
LA English
DT Article
ID POSTOPERATIVE CHYLOTHORAX; MR LYMPHOGRAPHY; LYMPHANGIOGRAPHY; DENDRIMER;
MS-325; MANAGEMENT; MOLECULES; AGENTS
AB Background-rationale: To investigate whether interstitial injection of gadofosveset trisodium (Ablavar (R), Lantheus Medical, North Billerica, MA) would be suitable for thoracic duct (TD) imaging in a pig model. Methods and Results: Gadofosveset trisodium alone or premixed with 10% human serum albumin (HSA) was administered intradermally in the extremities of pigs at varying doses to visualize the TD by MRI. Two blinded readers evaluated MRIs for TD visibility. The inter-observer variability for all MR imaging sessions was assessed using the Spearman rank correlation test. MR lymphography using gadofosveset trisodium premixed with HSA yielded superior visualization of the TD compared to gadofosveset trisodium alone, with a high inter-observer agreement (correlation coefficient of 0.88 (p=0.00000115)). Conclusions: We demonstrate that gadofosveset trisodium (premixed with 10%HSA) can be injected intradermally in order to perform MR lymphography of the thoracic duct. Since this agent is already FDA approved for MR imaging, the off-label use of it for imaging of the thoracic duct in humans is feasible, and the approach may prove to be beneficial for patients with TD abnormalities.
C1 [Turkbey, Baris; Kobayashi, Hisataka; Choyke, Peter L.; Nakajima, Takahito] NCI, Mol Imaging Program, Bethesda, MD 20892 USA.
[Hoyt, Robert F., Jr.] NHLBI, Lab Anim Med & Surg, NIH, Bethesda, MD 20892 USA.
[Griffiths, Gary L.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Clin Res Directorate CMRP, Frederick, MD USA.
[Bernardo, Marcelino] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Res Technol Program, Frederick, MD USA.
[Rialon, Kristy; Fishman, Steven J.; Sena, Laureen M.] Boston Children s Hosp, Boston, MA USA.
RP Turkbey, B (reprint author), NCI, Mol Imaging Program, 10 Ctr Dr MSC 1182 Bldg 10,Room B3B85, Bethesda, MD 20892 USA.
EM turkbeyi@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; Laura Marie Fazio and Taylor Robert Gladd PLE Fund;
Stuart and Jane Weitzman Vascular Anomalies Fund
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
Contract No. HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government.;
Additional funding was provided by the Laura Marie Fazio and Taylor
Robert Gladd PLE Fund and the Stuart and Jane Weitzman Vascular
Anomalies Fund.
NR 14
TC 3
Z9 3
U1 0
U2 1
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1539-6851
EI 1557-8585
J9 LYMPHAT RES BIOL
JI Lymphat. Res. Biol.
PD MAR 1
PY 2014
VL 12
IS 1
BP 32
EP 36
DI 10.1089/lrb.2013.0029
PG 5
WC Medicine, Research & Experimental; Physiology
SC Research & Experimental Medicine; Physiology
GA AE6JT
UT WOS:000334098600005
PM 24502282
ER
PT J
AU Townsend, SSM
Eliezer, D
Major, B
Mendes, WB
AF Townsend, Sarah S. M.
Eliezer, Dina
Major, Brenda
Mendes, Wendy Berry
TI Influencing the World Versus Adjusting to Constraints: Social Class
Moderates Responses to Discrimination
SO SOCIAL PSYCHOLOGICAL AND PERSONALITY SCIENCE
LA English
DT Article
DE socioeconomic status; prejudice; stress reactions; neuroendocrinology
ID SELF-ESTEEM; SOCIOECONOMIC-STATUS; HEALTH; STRESS; ATTRIBUTIONS;
PREJUDICE; AMERICAN; PATTERNS; CHOICE; ALWAYS
AB Although higher social class carries mental and physical health benefits, these advantages are less robust among members of racial and ethnic minority groups than among European Americans. We explore whether differential reactions to discrimination may be a factor in explaining why. Working-class and middle-class Latino American women engaged in an evaluative interaction with a European American woman who rejected them and held either prejudiced or unprejudiced attitudes. We examined how participants responded to this rejection by measuring neuroendocrine reactivity, executive functioning, and the affective content of their verbal responses during the interaction. Among middle-class Latinas, rejection from a prejudiced, compared to unprejudiced, out-group member was associated with less adaptive stress responses, greater cognitive depletion, and more feelings of uncertainty. In contrast, among working-class Latinas, neuroendocrine, cognitive, and affective responses were similar across the two sources of rejection. Results suggest that social class is an important moderator of responses to discrimination.
C1 [Townsend, Sarah S. M.] Northwestern Univ, Kellogg Sch Management, Evanston, IL 60208 USA.
[Eliezer, Dina] NIH, Bethesda, MD 20892 USA.
[Major, Brenda] Univ Calif Santa Barbara, Dept Psychol & Brain Sci, Santa Barbara, CA 93106 USA.
[Mendes, Wendy Berry] Univ Calif San Francisco, San Francisco, CA 94143 USA.
RP Townsend, SSM (reprint author), Northwestern Univ, Kellogg Sch Management, Dept Management & Org, Evanston, IL 60208 USA.
EM s-townsend@kellogg.northwestern.edu
NR 44
TC 4
Z9 4
U1 4
U2 10
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1948-5506
EI 1948-5514
J9 SOC PSYCHOL PERS SCI
JI Soc. Psychol. Personal Sci.
PD MAR
PY 2014
VL 5
IS 2
BP 226
EP 234
DI 10.1177/1948550613490968
PG 9
WC Psychology, Social
SC Psychology
GA AH9CI
UT WOS:000336437600012
ER
PT J
AU Austin, SK
Dowd, KA
AF Austin, S. Kyle
Dowd, Kimberly A.
TI B Cell Response and Mechanisms of Antibody Protection to West Nile Virus
SO VIRUSES-BASEL
LA English
DT Review
DE West Nile virus; flavivirus; humoral immunity; neutralizing antibody;
epitopes; therapeutics
ID FC-GAMMA-RECEPTOR; HUMANIZED MONOCLONAL-ANTIBODY; BORNE
ENCEPHALITIS-VIRUS; FUSION-LOOP ANTIBODY; ENVELOPE PROTEIN; DENGUE
VIRUS; CRYSTAL-STRUCTURE; NEUTRALIZING ANTIBODIES; MEDIATED
NEUTRALIZATION; FLAVIVIRUS INFECTION
AB West Nile virus (WNV) has become the principal cause of viral encephalitis in North America since its introduction in New York in 1999. This emerging virus is transmitted to humans via the bite of an infected mosquito. While there have been several candidates in clinical trials, there are no approved vaccines or WNV-specific therapies for the treatment of WNV disease in humans. From studies with small animal models and convalescent human patients, a great deal has been learned concerning the immune response to infection with WNV. Here, we provide an overview of a subset of that information regarding the humoral and antibody response generated during WNV infection.
C1 [Austin, S. Kyle] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
[Dowd, Kimberly A.] NIAID, NIH, Bethesda, MD 20892 USA.
RP Austin, SK (reprint author), Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
EM skaustin@DOM.wustl.edu; dowdka@mail.nih.gov
FU NIH [5R01AI098723]
FX This work was supported by the NIH intramural program and NIH Grant
5R01AI098723.
NR 109
TC 2
Z9 4
U1 1
U2 4
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1999-4915
J9 VIRUSES-BASEL
JI Viruses-Basel
PD MAR
PY 2014
VL 6
IS 3
BP 1015
EP 1036
DI 10.3390/v6031015
PG 22
WC Virology
SC Virology
GA AG9RC
UT WOS:000335756100005
PM 24594676
ER
PT J
AU Schountz, T
Prescott, J
AF Schountz, Tony
Prescott, Joseph
TI Hantavirus Immunology of Rodent Reservoirs: Current Status and Future
Directions
SO VIRUSES-BASEL
LA English
DT Review
DE hantavirus; rodent; immune response; ecoimmunology; zoonosis; systems
biology
ID SIN-NOMBRE-VIRUS; REGULATORY T-CELLS; MOUSE PEROMYSCUS-MANICULATUS;
CREEK-CANAL-VIRUS; VOLES CLETHRIONOMYS-GLAREOLUS; ALPHA-INDUCED
ACTIVATION; G1 CYTOPLASMIC TAIL; MALE NORWAY RATS; NF-KAPPA-B;
SEOUL-VIRUS
AB Hantaviruses are hosted by rodents, insectivores and bats. Several rodent-borne hantaviruses cause two diseases that share many features in humans, hemorrhagic fever with renal syndrome in Eurasia or hantavirus cardiopulmonary syndrome in the Americas. It is thought that the immune response plays a significant contributory role in these diseases. However, in reservoir hosts that have been closely examined, little or no pathology occurs and infection is persistent despite evidence of adaptive immune responses. Because most hantavirus reservoirs are not model organisms, it is difficult to conduct meaningful experiments that might shed light on how the viruses evade sterilizing immune responses and why immunopathology does not occur. Despite these limitations, recent advances in instrumentation and bioinformatics will have a dramatic impact on understanding reservoir host responses to hantaviruses by employing a systems biology approach to identify important pathways that mediate virus/reservoir relationships.
C1 [Schountz, Tony] Colorado State Univ, Coll Vet Med, Dept Microbiol Immunol & Pathol, Arthropod Borne & Infect Dis Lab, Ft Collins, CO 80524 USA.
[Prescott, Joseph] NIAID, Virol Lab, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT 59840 USA.
RP Schountz, T (reprint author), Colorado State Univ, Coll Vet Med, Dept Microbiol Immunol & Pathol, Arthropod Borne & Infect Dis Lab, Ft Collins, CO 80524 USA.
EM tony.schountz@colostate.edu; prescottjb@niaid.nih.gov
FU Department of Microbiology, Immunology and Pathology, Colorado State
University; NIH [AI054461]; Intramural Program of NIAID, NIH
FX The authors thank Brian Hjelle, Charles H. Calisher, Rushika Perera and
Heinz Feldmann for helpful comments, support and advice leading to the
preparation of this manuscript. Support for this work was provided by
the Department of Microbiology, Immunology and Pathology, Colorado State
University (TS), NIH grant AI054461 (TS), and Intramural Program of
NIAID, NIH (JP).
NR 114
TC 7
Z9 7
U1 2
U2 24
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1999-4915
J9 VIRUSES-BASEL
JI Viruses-Basel
PD MAR
PY 2014
VL 6
IS 3
BP 1317
EP 1335
DI 10.3390/v6031317
PG 19
WC Virology
SC Virology
GA AG9RC
UT WOS:000335756100020
PM 24638205
ER
PT J
AU Das, S
Chigurupat, S
Mattson, MP
Self, WT
Seal, S
AF Das, S.
Chigurupat, S.
Mattson, M. P.
Self, W. T.
Seal, S.
TI NOVEL RARE EARTH OXIDE ACCELERATES ANGIOGENESIS AND WOUND HEALING BY
DECREASING OXIDATIVE STRESS AND CONTROLLING LOCAL OXYGEN ENVIRONMENT
SO WOUND REPAIR AND REGENERATION
LA English
DT Meeting Abstract
C1 [Das, S.; Self, W. T.; Seal, S.] Univ Cent Florida, Orlando, FL 32816 USA.
[Chigurupat, S.; Mattson, M. P.] NIA, Intramural Res Program, Baltimore, MD 21224 USA.
RI Self, William/A-6704-2008
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1067-1927
EI 1524-475X
J9 WOUND REPAIR REGEN
JI Wound Repair Regen.
PD MAR
PY 2014
VL 22
IS 2
BP A37
EP A37
PG 1
WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery
SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery
GA AC9DV
UT WOS:000332835400041
ER
PT J
AU Wynn, TA
AF Wynn, T. A.
TI IMMUNOLOGICAL MECHANISMS OF FIBROSIS
SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY
LA English
DT Meeting Abstract
C1 [Wynn, T. A.] NIAID, Program Tissue Immun & Repair, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CLINICAL & EXPER RHEUMATOLOGY
PI PISA
PA VIA SANTA MARIA 31, 56126 PISA, ITALY
SN 0392-856X
J9 CLIN EXP RHEUMATOL
JI Clin. Exp. Rheumatol.
PD MAR-APR
PY 2014
VL 32
IS 2
SU 81
BP S11
EP S11
PG 1
WC Rheumatology
SC Rheumatology
GA AH2FH
UT WOS:000335936400017
ER
PT J
AU Csoka, B
Koscso, B
Toro, G
Kokai, E
Virag, L
Nemeth, ZH
Pacher, P
Bai, P
Hasko, G
AF Csoka, Balazs
Koscso, Balazs
Toero, Gabor
Kokai, Endre
Virag, Laszlo
Nemeth, Zoltan H.
Pacher, Pal
Bai, Peter
Hasko, Gyoergy
TI A2B Adenosine Receptors Prevent Insulin Resistance by Inhibiting Adipose
Tissue Inflammation via Maintaining Alternative Macrophage Activation
SO DIABETES
LA English
DT Article
ID NECROSIS-FACTOR-ALPHA; BODY-MASS INDEX; A(2B) RECEPTORS; MEDIATED
INFLAMMATION; OXIDATIVE-METABOLISM; GLUCOSE-HOMEOSTASIS; IL-10
PRODUCTION; INNATE IMMUNITY; OBESITY; CELLS
C1 [Csoka, Balazs; Koscso, Balazs; Nemeth, Zoltan H.; Hasko, Gyoergy] Rutgers New Jersey Med Sch, Dept Surg, Newark, NJ USA.
[Toero, Gabor; Kokai, Endre; Virag, Laszlo; Bai, Peter; Hasko, Gyoergy] Univ Debrecen, Dept Med Chem, Med & Hlth Sci Ctr, H-4012 Debrecen, Hungary.
[Virag, Laszlo; Bai, Peter] Hungarian Acad Sci, Cell Biol & Signalling Res Grp, Debrecen, Hungary.
[Nemeth, Zoltan H.] Morristown Med Ctr, Dept Surg, Morristown, NJ USA.
[Pacher, Pal] NIAAA, Bethesda, MD USA.
RP Csoka, B (reprint author), Rutgers New Jersey Med Sch, Dept Surg, Newark, NJ USA.
EM csokaba@njms.rutgers.edu; haskoge@njms.rutgers.edu
RI Pacher, Pal/B-6378-2008;
OI Pacher, Pal/0000-0001-7036-8108; Csoka, Balazs/0000-0002-7562-1130
FU National Institutes of Health [R01GM66189]; U.S. Army Medical Research
and Materiel Command grant [09065004/W81XWH-10-1-1015]; Hungarian
Scientific Research Fund Grants (OTKA) [PD83473, K108308, CK 78275,
K109178, MB08-1-2011-0015 84685]; National Institutes of Health,
National Institute on Alcohol Abuse and Alcoholism; Bolyai fellowship;
National Innovation Office [TeT_09-2010-0023,
TaMOP-4.2.2/A-11/1/KONV-2012-0025, TaMOP-4.2.1/B-09/KONV-2010-0007,
TaMOP-4.2.2/B-10/1-2010-0024]; Medical and Health Science Center
[Mecenatura Mec-8/2011]
FX This work was supported by National Institutes of Health grant
R01GM66189 (G.H.); U.S. Army Medical Research and Materiel Command grant
09065004/W81XWH-10-1-1015 (G.H.); Hungarian Scientific Research Fund
Grants (OTKA) PD83473 and K108308 (P.B.), CK 78275 and K109178 (G.H.),
and Human MB08-1-2011-0015 84685 (E.K.); the Intramural Research Program
of the National Institutes of Health, National Institute on Alcohol
Abuse and Alcoholism (P.P.); a Bolyai fellowship (P.B.); National
Innovation Office (Baross program Seahorse grant, TeT_09-2010-0023)
grants TaMOP-4.2.2/A-11/1/KONV-2012-0025,
TaMOP-4.2.1/B-09/KONV-2010-0007, and TaMOP-4.2.2/B-10/1-2010-0024; and a
grant from the Medical and Health Science Center (Mecenatura
Mec-8/2011).
NR 58
TC 14
Z9 15
U1 0
U2 4
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
EI 1939-327X
J9 DIABETES
JI Diabetes
PD MAR
PY 2014
VL 63
IS 3
BP 850
EP 866
PG 17
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AB2HQ
UT WOS:000331614200008
PM 24194503
ER
PT J
AU Walters, DM
White, KM
Patel, U
Davis, MJ
Veluci-Marlow, RM
Sunkesula, SRB
Bonner, JC
Martin, JR
Gladwell, W
Kleeberger, SR
AF Walters, Dianne M.
White, Kevin M.
Patel, Ushma
Davis, Martin J.
Veluci-Marlow, Roberta M.
Sunkesula, Solomon Raju Bhupanapadu
Bonner, James C.
Martin, Jessica R.
Gladwell, Wes
Kleeberger, Steven R.
TI Genetic susceptibility to interstitial pulmonary fibrosis in mice
induced by vanadium pentoxide (V2O5)
SO FASEB JOURNAL
LA English
DT Article
DE lung injury; inflammation; collagen; haplotype; mapping
ID HUMAN LUNG FIBROBLASTS; FUEL-OIL ASH; MESSENGER-RNA EXPRESSION;
BRONCHOALVEOLAR LAVAGE; ALVEOLAR MACROPHAGES; EOSINOPHIL ACTIVATION;
GROWTH-FACTOR; ANIMAL-MODEL; INFLAMMATION; BETA
AB Interstitial lung diseases (ILDs) are characterized by injury, inflammation, and scarring of alveoli, leading to impaired function. The etiology of idiopathic forms of ILD is not understood, making them particularly difficult to study due to the lack of appropriate animal models. Consequently, few effective therapies have emerged. We developed an inbred mouse model of ILD using vanadium pentoxide (V2O5), the most common form of a transition metal found in cigarette smoke, fuel ash, mineral ores, and steel alloys. Pulmonary responses to V2O5, including dose-dependent increases in lung permeability, inflammation, collagen content, and dysfunction, were significantly greater in DBA/2J mice compared to C57BL/6J mice. Inflammatory and fibrotic responses persisted for 4 mo in DBA/2J mice, while limited responses in C57BL/6J mice resolved. We investigated the genetic basis for differential responses through genetic mapping of V2O5-induced lung collagen content in BXD recombinant inbred (RI) strains and identified significant linkage on chromosome 4 with candidate genes that associate with V2O5-induced collagen content across the RI strains. Results suggest that V2O5 may induce pulmonary fibrosis through mechanisms distinct from those in other models of pulmonary fibrosis. These findings should further advance our understanding of mechanisms involved in ILD and thereby aid in identification of new therapeutic targets.Walters, D. M., White, K. M., Patel, U., Davis, M. J., Veluci-Marlow, R. M., Bhupanapadu Sunkesula, S. R., Bonner, J. C., Martin, J. R., Gladwell, W., Kleeberger, S. R. Genetic susceptibility to interstitial pulmonary fibrosis in mice induced by vanadium pentoxide (V2O5).
C1 [Walters, Dianne M.; White, Kevin M.; Patel, Ushma; Davis, Martin J.; Veluci-Marlow, Roberta M.; Sunkesula, Solomon Raju Bhupanapadu] E Carolina Univ, Dept Physiol, Greenville, NC 27834 USA.
[Bonner, James C.] N Carolina State Univ, Dept Biol Sci, Raleigh, NC 27695 USA.
[Martin, Jessica R.; Gladwell, Wes; Kleeberger, Steven R.] NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA.
RP Walters, DM (reprint author), E Carolina Univ, Brody Sch Med, Dept Physiol, 6N-98,600 Moye Blvd, Greenville, NC 27834 USA.
EM waltersd@ecu.edu
FU Intramural Research Program of the U.S. National Institutes of Health;
NIEHS; East Carolina University
FX The authors gratefully acknowledge the U.S. National Institute of
Environmental Health Sciences (NIEHS) Histology Core facility and Joani
Zary Oswald (Brody School of Medicine Histology Core, East Carolina
University) for histological services, and Dr. Paul Strausbauch for
pathology advice. The authors also thank Dr. Jared M. Brown for use of
laboratory equipment and technical advice, and M. Anthony Phipps for
technical assistance. This research was supported (in part) by the
Intramural Research Program of the U.S. National Institutes of Health,
NIEHS, and East Carolina University. The authors declare no conflicts of
interest.
NR 72
TC 2
Z9 2
U1 2
U2 6
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
EI 1530-6860
J9 FASEB J
JI Faseb J.
PD MAR
PY 2014
VL 28
IS 3
BP 1098
EP 1112
DI 10.1096/fj.13-235044
PG 15
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA AG3MY
UT WOS:000335324800007
PM 24285090
ER
PT J
AU Suzuki, N
Numakawa, T
Chou, J
Vega, S
Mizuniwa, C
Sekimoto, K
Adachi, N
Kunugi, H
Arikawa-Hirasawa, E
Yamada, Y
Akazawa, C
AF Suzuki, Nobuharu
Numakawa, Tadahiro
Chou, Joshua
de Vega, Susana
Mizuniwa, Chihiro
Sekimoto, Kaori
Adachi, Naoki
Kunugi, Hiroshi
Arikawa-Hirasawa, Eri
Yamada, Yoshihiko
Akazawa, Chihiro
TI Teneurin-4 promotes cellular protrusion formation and neurite outgrowth
through focal adhesion kinase signaling
SO FASEB JOURNAL
LA English
DT Article
DE neuronal differentiation; cytoskeleton
ID PAIR-RULE GENE; BIPOLAR DISORDER; GROWTH CONE; FILOPODIA; CDC42;
PROTEINS; REGULATOR; NEURONS; FAMILY; CELLS
AB Teneurin-4 (Ten-4), a transmembrane protein, is highly expressed in the central nervous system; however, its cellular and molecular function in neuronal differentiation remains unknown. In this study, we aimed to elucidate the function of Ten-4 in neurite outgrowth. Ten-4 expression was induced during neurite outgrowth of the neuroblastoma cell line Neuro-2a. Ten-4 protein was localized at the neurite growth cones. Knockdown of Ten-4 expression in Neuro-2a cells decreased the formation of the filopodia-like protrusions and the length of individual neurites. Conversely, overexpression of Ten-4 promoted filopodia-like protrusion formation. In addition, knockdown and overexpression of Ten-4 reduced and elevated the activation of focal adhesion kinase (FAK) and Rho-family small GTPases, Cdc42 and Rac1, key molecules for the membranous protrusion formation downstream of FAK, respectively. Inhibition of the activation of FAK and neural Wiskott-Aldrich syndrome protein (N-WASP), which is a downstream regulator of FAK and Cdc42, blocked protrusion formation by Ten-4 overexpression. Further, Ten-4 colocalized with phosphorylated FAK in the filopodia-like protrusion regions. Together, our findings show that Ten-4 is a novel positive regulator of cellular protrusion formation and neurite outgrowth through the FAK signaling pathway.Suzuki, N., Numakawa, T., Chou, J., de Vega, S., Mizuniwa, C., Sekimoto, K., Adachi, N., Kunugi, H., Arikawa-Hirasawa, E., Yamada, Y., Akazawa, C. Teneurin-4 promotes cellular protrusion formation and neurite outgrowth through focal adhesion kinase signaling.
C1 [Suzuki, Nobuharu; Mizuniwa, Chihiro; Sekimoto, Kaori; Akazawa, Chihiro] Tokyo Med & Dent Univ, Grad Sch Hlth Care Sci, Dept Biochem & Biophys, Tokyo 1138510, Japan.
[Suzuki, Nobuharu; Chou, Joshua; de Vega, Susana; Yamada, Yoshihiko] Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD USA.
[Numakawa, Tadahiro; Adachi, Naoki; Kunugi, Hiroshi] Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Dept Mental Disorder Res, Tokyo, Japan.
[de Vega, Susana; Arikawa-Hirasawa, Eri] Juntendo Univ, Res Inst Dis Old Age, Fac Med, Tokyo, Japan.
[de Vega, Susana; Arikawa-Hirasawa, Eri] Juntendo Univ, Dept Neurol, Fac Med, Tokyo, Japan.
RP Akazawa, C (reprint author), Tokyo Med & Dent Univ, Grad Sch Hlth Care Sci, Dept Biochem & Biophys, Bunkyo Ku, 1-5-45 Yushima,Bldg 3, Tokyo 1138510, Japan.
EM c.akazawa.bb@tmd.ac.jp
FU Intramural Research Program of the National Institute of Dental and
Craniofacial Research, U.S. National Institutes of Health; Ministry of
Education, Culture, Sports, Science, and Technology (MEXT) of Japan
[24300139]; MEXT Program for Strategic Research Foundation at Private
Universities; MEXT [25860701]; Ministry of Health, Labor, and Welfare of
Japan [23040101]
FX The authors thank Dr. Yukiko Goda (RIKEN BSI, Wako, Japan) for her
valuable suggestion. This work was supported by the Intramural Research
Program of the National Institute of Dental and Craniofacial Research,
U.S. National Institutes of Health (Y.Y.), a Grant-in-Aid for Scientific
Research (B) from the Ministry of Education, Culture, Sports, Science,
and Technology (MEXT) of Japan (24300139; T.N.), the MEXT Program for
Strategic Research Foundation at Private Universities 2011-2015 (S. V.
and E. A-H.), a Grant-in-Aid for Young Scientists from MEXT (25860701;
N.S.), and a Grant-in-Aid from the Ministry of Health, Labor, and
Welfare of Japan (23040101; C. A.).
NR 33
TC 7
Z9 7
U1 0
U2 5
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
EI 1530-6860
J9 FASEB J
JI Faseb J.
PD MAR
PY 2014
VL 28
IS 3
BP 1386
EP 1397
DI 10.1096/fj.13-241034
PG 12
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA AG3MY
UT WOS:000335324800030
PM 24344332
ER
PT J
AU Di Michele, DM
Gibb, C
Lefkowitz, JM
Ni, Q
Gerber, LM
Ganguly, A
AF Di Michele, D. M.
Gibb, C.
Lefkowitz, J. M.
Ni, Q.
Gerber, L. M.
Ganguly, A.
TI Severe and moderate haemophilia A and B in US females
SO HAEMOPHILIA
LA English
DT Article
ID X-CHROMOSOME INACTIVATION; QUALITY-OF-LIFE; INHERITED BLEEDING
DISORDERS; FACTOR-IX DEFICIENCY; FACTOR-VIII; MUTATION; GENE; PATTERNS;
CARRIERS; MANIFESTATIONS
C1 [Di Michele, D. M.; Gibb, C.] Weill Cornell Med Coll, Dept Pediat, New York, NY USA.
[Lefkowitz, J. M.] New York Presbyterian Hosp, Weill Cornell Med Ctr, Dept Social Work, New York, NY USA.
[Ni, Q.; Gerber, L. M.] Weill Cornell Med Coll, Dept Publ Hlth, New York, NY USA.
[Ganguly, A.] Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA.
RP Di Michele, DM (reprint author), NHLBI, Div Blood Dis & Resources, NIH, 6701 Rockledge Dr,Room 9132, Bethesda, MD 20892 USA.
EM dimicheledm@nhlbi.nih.gov
FU CSL-Behring(R); National Hemophilia Foundation Social Work Excellence
Fellowship award
FX This study was funded by an unrestricted grant from CSL-Behring (R) and
by a National Hemophilia Foundation Social Work Excellence Fellowship
award. The authors thank the participating centre directors and their
staff: Thomas Abshire; Lisa Boggio; Alice Cohen; Nadia P. Ewing; Ralph
Gruppo; Keith Hoots; Jeffrey Hord; Barbara Konkle; Peter Kouides; Philip
Kuriakose; Richard Lipton; Marilyn Manco-Johnson; Ellis Neufeld; Idith
Ortiz; Mary Jane Petruzzi; Edward Romond; Charles Sexauer. We also thank
Andra James for her thoughtful review of this manuscript.
NR 42
TC 8
Z9 8
U1 0
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1351-8216
EI 1365-2516
J9 HAEMOPHILIA
JI Haemophilia
PD MAR
PY 2014
VL 20
IS 2
BP E136
EP E143
PG 8
WC Hematology
SC Hematology
GA AB0CO
UT WOS:000331459600004
PM 24533955
ER
PT J
AU Lozier, JN
Nghiem, K
Lee, M
Hodsdon, B
Joe, G
Weitzel, RP
Tisdale, JF
Hsieh, M
AF Lozier, J. N.
Nghiem, K.
Lee, M.
Hodsdon, B.
Joe, g.
Weitzel, R. P.
Tisdale, J. F.
Hsieh, M.
TI Acquired haemophilia A after stem cell transplant for sickle cell
disease: treatment with recombinant porcine factor VIII (OBI-1) and
tolerance induction with rituximab/prednisone
SO HAEMOPHILIA
LA English
DT Letter
ID ANTIBODIES; INHIBITORS
C1 [Lozier, J. N.; Nghiem, K.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
[Lee, M.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA.
[Hodsdon, B.; Joe, g.] NIH, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA.
[Weitzel, R. P.; Tisdale, J. F.; Hsieh, M.] NHLBI, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA.
RP Lozier, JN (reprint author), Bldg 10,Room 2C306,MSC 1508,10 Ctr Dr, Bethesda, MD 20892 USA.
EM lozierjn@cc.nih.gov
FU Intramural NIH HHS
NR 8
TC 6
Z9 6
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1351-8216
EI 1365-2516
J9 HAEMOPHILIA
JI Haemophilia
PD MAR
PY 2014
VL 20
IS 2
BP E185
EP E188
PG 4
WC Hematology
SC Hematology
GA AB0CO
UT WOS:000331459600020
PM 24533959
ER
PT J
AU Cheng, J
Fang, ZZ
Kim, JH
Krausz, KW
Tanaka, N
Chiang, JYL
Gonzalez, FJ
AF Cheng, Jie
Fang, Zhong-Ze
Kim, Jung-Hwan
Krausz, Kristopher W.
Tanaka, Naoki
Chiang, John Y. L.
Gonzalez, Frank J.
TI Intestinal CYP3A4 protects against lithocholic acid-induced
hepatotoxicity in intestine-specific VDR-deficient mice
SO JOURNAL OF LIPID RESEARCH
LA English
DT Article
DE bile acids; vitamin D receptor; metabolomics
ID VITAMIN-D-RECEPTOR; BILE-ACID; 1,25-DIHYDROXYVITAMIN D-3;
CYTOCHROME-P450 3A4; PERMEABILITY; DISEASE; ABSORPTION; EXPRESSION
AB Vitamin D receptor (VDR) mediates vitamin D signaling involved in bone metabolism, cellular growth and differentiation, cardiovascular function, and bile acid regulation. Mice with an intestine-specific disruption of VDR (Vdr(Delta IEpC)) have abnormal body size, colon structure, and imbalance of bile acid metabolism. Lithocholic acid (LCA), a secondary bile acid that activates VDR, is among the most toxic of the bile acids that when overaccumulated in the liver causes hepatotoxicity. Because cytochrome P450 3A4 (CYP3A4) is a target gene of VDR-involved bile acid metabolism, the role of CYP3A4 in VDR biology and bile acid metabolism was investigated. The CYP3A4 gene was inserted into Vdr(Delta IEpC) mice to produce the Vdr(Delta IEpC)/3A4 line. LCA was administered to control, transgenic-CYP3A4, Vdr(Delta IEpC), and Vdr(Delta IEpC)/3A4 mice, and hepatic toxicity and bile acid levels in the liver, intestine, bile, and urine were measured. VDR deficiency in the intestine of the Vdr(Delta IEpC) mice exacerbates LCA-induced hepatotoxicity manifested by increased necrosis and inflammation, due in part to over-accumulation of hepatic bile acids including taurocholic acid and taurodeoxycholic acid. Intestinal expression of CYP3A4 in the Vdr(Delta IEpC)/3A4 mouse line reduces LCA-induced hepatotoxicity through elevation of LCA metabolism and detoxification, and suppression of bile acid transporter expression in the small intestine.(jlr) This study reveals that intestinal CYP3A4 protects against LCA hepatotoxicity.
C1 [Cheng, Jie; Fang, Zhong-Ze; Kim, Jung-Hwan; Krausz, Kristopher W.; Tanaka, Naoki; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Cheng, Jie; Chiang, John Y. L.] Northeast Ohio Med Univ, Dept Integrat Med Sci, Rootstown, OH 44272 USA.
RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM gonzalef@mail.nih.gov
OI Chiang, John/0000-0001-9360-7650
FU National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health [R37DK058379, R01DK044442]; National
Cancer Institute
FX This work was funded by the National Cancer Institute Intramural
Research Program, and by grants R37DK058379 and R01DK044442 to J.Y.L.C.
from the National Institute of Diabetes and Digestive and Kidney
Diseases, National Institutes of Health.
NR 32
TC 15
Z9 15
U1 1
U2 19
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0022-2275
EI 1539-7262
J9 J LIPID RES
JI J. Lipid Res.
PD MAR
PY 2014
VL 55
IS 3
BP 455
EP 465
DI 10.1194/jlr.M044420
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AH8YX
UT WOS:000336425300010
PM 24343899
ER
PT J
AU Wakabayashi, KT
Kiyatkin, EA
AF Wakabayashi, Ken T.
Kiyatkin, Eugene A.
TI Critical role of peripheral drug actions in experience-dependent changes
in nucleus accumbens glutamate release induced by intravenous cocaine
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE electrochemistry; enzyme-based glutamate biosensors;
experience-dependent neuroplasticity of glutamate neurotransmission;
glutamate release; peripheral actions of cocaine
ID VENTRAL TEGMENTAL AREA; ACID TRANSPORTER FAMILY; HIGH-AFFINITY
GLUTAMATE; DOPAMINE UPTAKE; IN-VIVO; EXTRACELLULAR GLUTAMATE; ADDICTION;
RATS; SENSITIZATION; TRANSMISSION
AB Recent studies reveal that cocaine experience results in persistent neuroadaptive changes within glutamate (Glu) synapses in brain areas associated with drug reward. However, it remains unclear whether cocaine affects Glu release in drug-naive animals and how it is altered by drug experience. Using high-speed amperometry with enzyme-based and enzyme-free biosensors in freely moving rats, we show that an initial intravenous cocaine injection at a low self-administering dose (1mg/kg) induces rapid, small and transient Glu release in the nucleus accumbens shell (NAc), which with subsequent injections rapidly becomes a much stronger, two-component increase. Using cocaine-methiodide, cocaine's analog that does not cross the blood-brain barrier, we confirm that the initial cocaine-induced Glu release in the NAc has a peripheral neural origin. Unlike cocaine, Glu responses induced by cocaine-methiodide rapidly habituate following repeated exposure. However, after cocaine experience this drug induces cocaine-like Glu responses. Hence, the interoceptive actions of cocaine, which essentially precede its direct actions in the brain, play a critical role in experience-dependent alterations in Glu release, cocaine-induced neural sensitization and may contribute to cocaine addiction.
Using high-speed amperometry with enzyme-based biosensors in freely moving rats, we show that initial intravenous cocaine induces rapid, transient glutamate (Glu) release in the Nac (Nucleus accumbens), rapidly becoming a stronger, two-component increase with subsequent injections. We show that the peripheral actions of cocaine, which precedes its direct central actions, play a critical role in experience-dependent alterations in Glu release, possibly contributing to cocaine addiction.
C1 [Wakabayashi, Ken T.; Kiyatkin, Eugene A.] NIDA, In Vivo Electrophysiol Unit, Behav Neurosci Branch, Intramural Res Program,NIH,DHHS, Baltimore, MD 21224 USA.
RP Kiyatkin, EA (reprint author), NIDA, In Vivo Electrophysiol Unit, Behav Neurosci Branch, Intramural Res Program,NIH,DHHS, 333 Cassell Dr, Baltimore, MD 21224 USA.
EM ekiyatki@intra.nida.nih.gov
FU Intramural Research Program of NIDA-IRP
FX We thank Drs A. Bonci, C. Lupica, and T. Robinson for helpful
suggestions regarding this manuscript. We also appreciate editorial
assistance of Ms. Stephanie Myal. This study was supported by the
Intramural Research Program of NIDA-IRP. The Authors declare no
competitive interests in relation to the work described. EAK supervised
the project. KTW and EAK performed experiments, wrote the manuscript and
both have approved the submission of this version.
NR 60
TC 10
Z9 10
U1 1
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3042
EI 1471-4159
J9 J NEUROCHEM
JI J. Neurochem.
PD MAR
PY 2014
VL 128
IS 5
BP 672
EP 685
DI 10.1111/jnc.12472
PG 14
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA AB1KX
UT WOS:000331551600007
PM 24111505
ER
PT J
AU Alagaili, AN
Briese, T
Mishra, N
Kapoor, V
Sameroff, SC
de Wit, E
Munster, VJ
Hensley, LE
Zalmout, IS
Kapoor, A
Epstein, JH
Karesh, WB
Daszak, P
Mohammed, OB
Lipkin, WI
AF Alagaili, Abdulaziz N.
Briese, Thomas
Mishra, Nischay
Kapoor, Vishal
Sameroff, Stephen C.
de Wit, Emmie
Munster, Vincent J.
Hensley, Lisa E.
Zalmout, Iyad S.
Kapoor, Amit
Epstein, Jonathan H.
Karesh, William B.
Daszak, Peter
Mohammed, Osama B.
Lipkin, W. Ian
TI Middle East Respiratory Syndrome Coronavirus Infection in Dromedary
Camels in Saudi Arabia
SO MBIO
LA English
DT Article
ID BATS
AB The Middle East respiratory syndrome (MERS) is proposed to be a zoonotic disease; however, the reservoir and mechanism for transmission of the causative agent, the MERS coronavirus, are unknown. Dromedary camels have been implicated through reports that some victims have been exposed to camels, camels in areas where the disease has emerged have antibodies to the virus, and viral sequences have been recovered from camels in association with outbreaks of the disease among humans. Nonetheless, whether camels mediate transmission to humans is unresolved. Here we provide evidence from a geographic and temporal survey of camels in the Kingdom of Saudi Arabia that MERS coronaviruses have been circulating in camels since at least 1992, are distributed countrywide, and can be phylogenetically classified into clades that correlate with outbreaks of the disease among humans. We found no evidence of infection in domestic sheep or domestic goats.
IMPORTANCE This study was undertaken to determine the historical and current prevalence of Middle East respiratory syndrome (MERS) coronavirus infection in dromedary camels and other livestock in the Kingdom of Saudi Arabia, where the index case and the majority of cases of MERS have been reported.
C1 [Alagaili, Abdulaziz N.; Zalmout, Iyad S.; Mohammed, Osama B.] King Saud Univ, Coll Med, Dept Zool, KSU Mammals Res Chair, Riyadh 11461, Saudi Arabia.
[Alagaili, Abdulaziz N.] Saudi Wildlife Author, Riyadh, Saudi Arabia.
[Briese, Thomas; Mishra, Nischay; Kapoor, Vishal; Sameroff, Stephen C.; Kapoor, Amit; Lipkin, W. Ian] Columbia Univ, Mailman Sch Publ Hlth, Ctr Infect & Immun, New York, NY USA.
[de Wit, Emmie; Munster, Vincent J.] NIAID, Virol Lab, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT USA.
[Hensley, Lisa E.] NIAID, Integrated Res Facil, NIH, Frederick, MD USA.
[Epstein, Jonathan H.; Karesh, William B.; Daszak, Peter] EcoHlth Alliance, New York, NY USA.
RP Alagaili, AN (reprint author), King Saud Univ, Coll Med, Dept Zool, KSU Mammals Res Chair, Riyadh 11461, Saudi Arabia.
EM aalagaili@ksu.edu.sa; tb2047@columbia.edu
OI de Wit, Emmie/0000-0002-9763-7758; Munster, Vincent/0000-0002-2288-3196
FU Deanship of Scientific Research, King Saud University; National
Institutes of Health [AI057158]; United States Agency for International
Development Emerging Pandemic Threats program, PREDICT project
[GHN-A-OO-09-00010-00]; Intramural Research Program of the National
Institute of Allergy and Infectious Diseases, National Institutes of
Health
FX The KSU Mammals Research Chair is supported by the Deanship of
Scientific Research, King Saud University. Work in the Center for
Infection and Immunity and EcoHealth Alliance is supported by awards
from the National Institutes of Health (AI057158) and the United States
Agency for International Development Emerging Pandemic Threats program,
PREDICT project, under the terms of cooperative agreement
GHN-A-OO-09-00010-00. Work in the Rocky Mountain Laboratories (E. de
Wit, V. J. Munster) and Integrated Research Facility (L. E. Hensley) was
supported by the Intramural Research Program of the National Institute
of Allergy and Infectious Diseases, National Institutes of Health.
NR 19
TC 39
Z9 47
U1 0
U2 22
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2150-7511
J9 MBIO
JI mBio
PD MAR-APR
PY 2014
VL 5
IS 2
AR e00884-14
DI 10.1128/mBio.00884-14
PG 6
WC Microbiology
SC Microbiology
GA AH1XR
UT WOS:000335915600002
PM 24570370
ER
PT J
AU Hayes, BM
Dulebohn, DP
Sarkar, A
Tilly, K
Bestor, A
Ambroggio, X
Rosa, PA
AF Hayes, Beth M.
Dulebohn, Daniel P.
Sarkar, Amit
Tilly, Kit
Bestor, Aaron
Ambroggio, Xavier
Rosa, Patricia A.
TI Regulatory Protein BBD18 of the Lyme Disease Spirochete: Essential Role
During Tick Acquisition?
SO MBIO
LA English
DT Article
ID OUTER-SURFACE PROTEIN; BORRELIA-BURGDORFERI GENES; LINEAR PLASMID LP17;
TARGETED DELETION; MAMMALIAN HOST; IMMUNE EVASION; OSPC OPERATOR; RPOS;
EXPRESSION; INFECTION
AB The Lyme disease spirochete Borrelia burgdorferi senses and responds to environmental cues as it transits between the tick vector and vertebrate host. Failure to properly adapt can block transmission of the spirochete and persistence in either vector or host. We previously identified BBD18, a novel plasmid-encoded protein of B. burgdorferi, as a putative repressor of the host-essential factor OspC. In this study, we investigate the in vivo role of BBD18 as a regulatory protein, using an experimental mouse-tick model system that closely resembles the natural infectious cycle of B. burgdorferi. We show that spirochetes that have been engineered to constitutively produce BBD18 can colonize and persist in ticks but do not infect mice when introduced by either tick bite or needle inoculation. Conversely, spirochetes lacking BBD18 can persistently infect mice but are not acquired by feeding ticks. Through site-directed mutagenesis, we have demonstrated that abrogation of spirochete infection in mice by overexpression of BBD18 occurs only with bbd18 alleles that can suppress OspC synthesis. Finally, we demonstrate that BBD18-mediated regulation does not utilize a previously described ospC operator sequence required by B. burgdorferi for persistence in immunocompetent mice. These data lead us to conclude that BBD18 does not represent the putative repressor utilized by B. burgdorferi for the specific downregulation of OspC in the mammalian host. Rather, we suggest that BBD18 exhibits features more consistent with those of a global regulatory protein whose critical role occurs during spirochete acquisition by feeding ticks.
IMPORTANCE Lyme disease, caused by Borrelia burgdorferi, is the most common arthropod-borne disease in North America. B. burgdorferi is transmitted to humans and other vertebrate hosts by ticks as they take a blood meal. Transmission between vectors and hosts requires the bacterium to sense changes in the environment and adapt. However, the mechanisms involved in this process are not well understood. By determining how B. burgdorferi cycles between two very different environments, we can potentially establish novel ways to interfere with transmission and limit infection of this vector-borne pathogen. We are studying a regulatory protein called BBD18 that we recently described. We found that too much BBD18 interferes with the spirochete's ability to establish infection in mice, whereas too little BBD18 appears to prevent colonization in ticks. Our study provides new insight into key elements of the infectious cycle of the Lyme disease spirochete.
C1 [Hayes, Beth M.; Dulebohn, Daniel P.; Sarkar, Amit; Tilly, Kit; Bestor, Aaron; Rosa, Patricia A.] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
[Ambroggio, Xavier] NIAID, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, NIH, Bethesda, MD 20892 USA.
RP Rosa, PA (reprint author), NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
EM prosa@niaid.nih.gov
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 43
TC 3
Z9 3
U1 0
U2 10
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2150-7511
J9 MBIO
JI mBio
PD MAR-APR
PY 2014
VL 5
IS 2
AR e01017-14
DI 10.1128/mBio.01017-14
PG 12
WC Microbiology
SC Microbiology
GA AH1XR
UT WOS:000335915600025
PM 24692636
ER
PT J
AU Hu, G
Chen, SH
Qiu, J
Bennett, JE
Myers, TG
Williamson, PR
AF Hu, Guowu
Chen, Shu Hui
Qiu, Jin
Bennett, John E.
Myers, Timothy G.
Williamson, Peter R.
TI Microevolution During Serial Mouse Passage Demonstrates FRE3 as a
Virulence Adaptation Gene in Cryptococcus neoformans
SO MBIO
LA English
DT Article
ID SACCHAROMYCES-CEREVISIAE; MOLECULAR CHARACTERIZATION; FUNGAL PATHOGENS;
IRON ACQUISITION; COPPER UPTAKE; VAR. GRUBII; INFECTION; MICE;
SUSCEPTIBILITY; EXPRESSION
AB Passage in mice of opportunistic pathogens such as Cryptococcus neoformans is known to increase virulence, but little is known about the molecular mechanisms involved in virulence adaptation. Serial mouse passage of nine environmental strains of serotype A C. neoformans identified two highly adapted virulent strains that showed a 4-fold reduction in time to death after four passages. Transcriptome sequencing expression studies demonstrated increased expression of a FRE3-encoded iron reductase in the two strains but not in a control strain that did not demonstrate increased virulence during mouse passage. FRE3 was shown to express an iron reductase activity and to play a role in iron-dependent growth of C. neoformans. Overexpression of FRE3 in the two original environmental strains increased growth in the macrophage cell line J774.16 and increased virulence. These data demonstrate a role for FRE3 in the virulence of C. neoformans and demonstrate how the increased expression of such a "virulence acquisition gene" during the environment-to-mammal transition, can optimize the virulence of environmental strains in mammalian hosts.
IMPORTANCE Cryptococcus neoformans is a significant global fungal pathogen that also resides in the environment. Recent studies have suggested that the organism may undergo microevolution in the host. However, little is known about the permitted genetic changes facilitating the adaptation of environmental strains to mammalian hosts. The present studies subjected environmental strains isolated from several metropolitan areas of the United States to serial passages in mice. Transcriptome sequencing expression studies identified the increased expression of an iron reductase gene, FRE3, in two strains that adapted in mice to become highly virulent, and overexpression of FRE3 recapitulated the increased virulence after mouse passage. Iron reductase in yeast is important to iron uptake in a large number of microbial pathogens. These studies demonstrate the capacity of C. neoformans to show reproducible changes in the expression levels of small numbers of genes termed "virulence adaptation genes" to effectively increase pathogenicity during the environment-to-mammal transition.
C1 [Hu, Guowu; Chen, Shu Hui; Qiu, Jin; Bennett, John E.; Williamson, Peter R.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Myers, Timothy G.] NIAID, Genom Technol Sect, Res Technol Branch, NIH, Bethesda, MD 20892 USA.
RP Williamson, PR (reprint author), NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM williamsonpr@mail.nih.gov
FU Intramural Research Program of the NIH, NIAID
FX This research was supported by the Intramural Research Program of the
NIH, NIAID.
NR 67
TC 4
Z9 4
U1 0
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2150-7511
J9 MBIO
JI mBio
PD MAR-APR
PY 2014
VL 5
IS 2
AR e00941-14
DI 10.1128/mBio.00941-14
PG 11
WC Microbiology
SC Microbiology
GA AH1XR
UT WOS:000335915600027
PM 24692633
ER
PT J
AU Ran, WQ
Kristensen, DM
Koonin, EV
AF Ran, Wenqi
Kristensen, David M.
Koonin, Eugene V.
TI Coupling Between Protein Level Selection and Codon Usage Optimization in
the Evolution of Bacteria and Archaea
SO MBIO
LA English
DT Article
ID ESCHERICHIA-COLI; TRANSLATIONAL ACCURACY; SEQUENCE EVOLUTION;
NATURAL-SELECTION; GENE-EXPRESSION; BIAS; GENOMES; DROSOPHILA;
MISTRANSLATION; SUBSTITUTION
AB The relationship between the selection affecting codon usage and selection on protein sequences of orthologous genes in diverse groups of bacteria and archaea was examined by using the Alignable Tight Genome Clusters database of prokaryote genomes. The codon usage bias is generally low, with 57.5% of the gene-specific optimal codon frequencies (Fopt) being below 0.55. This apparent weak selection on codon usage contrasts with the strong purifying selection on amino acid sequences, with 65.8% of the gene-specific dN/dS ratios being below 0.1. For most of the genomes compared, a limited but statistically significant negative correlation between Fopt and dN/dS was observed, which is indicative of a link between selection on protein sequence and selection on codon usage. The strength of the coupling between the protein level selection and codon usage bias showed a strong positive correlation with the genomic GC content. Combined with previous observations on the selection for GC-rich codons in bacteria and archaea with GC-rich genomes, these findings suggest that selection for translational fine-tuning could be an important factor in microbial evolution that drives the evolution of genome GC content away from mutational equilibrium. This type of selection is particularly pronounced in slowly evolving, "high-status" genes. A significantly stronger link between the two aspects of selection is observed in free-living bacteria than in parasitic bacteria and in genes encoding metabolic enzymes and transporters than in informational genes. These differences might reflect the special importance of translational fine-tuning for the adaptability of gene expression to environmental changes. The results of this work establish the coupling between protein level selection and selection for translational optimization as a distinct and potentially important factor in microbial evolution.
IMPORTANCE Selection affects the evolution of microbial genomes at many levels, including both the structure of proteins and the regulation of their production. Here we demonstrate the coupling between the selection on protein sequences and the optimization of codon usage in a broad range of bacteria and archaea. The strength of this coupling varies over a wide range and strongly and positively correlates with the genomic GC content. The cause(s) of the evolution of high GC content is a long-standing open question, given the universal mutational bias toward AT. We propose that optimization of codon usage could be one of the key factors that determine the evolution of GC-rich genomes. This work establishes the coupling between selection at the level of protein sequence and at the level of codon choice optimization as a distinct aspect of genome evolution.
C1 [Ran, Wenqi; Kristensen, David M.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
EM koonin@ncbi.nlm.nih.gov
FU U.S. Department of Health and Human Services
FX Our research is funded through the intramural fund of the U.S.
Department of Health and Human Services (to the National Library of
Medicine).
NR 65
TC 9
Z9 9
U1 1
U2 13
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2150-7511
J9 MBIO
JI mBio
PD MAR-APR
PY 2014
VL 5
IS 2
AR e00956-14
DI 10.1128/mBio.00956-14
PG 11
WC Microbiology
SC Microbiology
GA AH1XR
UT WOS:000335915600039
PM 24667707
ER
PT J
AU Saijo, T
Chen, JH
Chen, SCA
Rosen, LB
Yi, J
Sorrell, TC
Bennett, JE
Holland, SM
Browne, SK
Kwon-Chung, KJ
AF Saijo, Tomomi
Chen, Jianghan
Chen, Sharon C. -A.
Rosen, Lindsey B.
Yi, Jin
Sorrell, Tania C.
Bennett, John E.
Holland, Steven M.
Browne, Sarah K.
Kwon-Chung, Kyung J.
TI Anti-Granulocyte-Macrophage Colony-Stimulating Factor Autoantibodies Are
a Risk Factor for Central Nervous System Infection by Cryptococcus
gattii in Otherwise Immunocompetent Patients
SO MBIO
LA English
DT Article
ID PULMONARY ALVEOLAR PROTEINOSIS; HIV-ASSOCIATED CRYPTOCOCCOSIS; GM-CSF
AUTOANTIBODIES; NEOFORMANS INFECTION; IMMUNE-RESPONSE; DENDRITIC CELLS;
IN-VITRO; MICE; PARASITISM; DISEASE
AB Cryptococcosis is caused by either Cryptococcus neoformans or C. gattii. While cryptococcal meningoencephalitis is caused mostly by C. neoformans in immunocompromised patients, the risk factors remain unclear for patients with no known immune defect. Recently, anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies were detected in the plasma of seven "immunocompetent" cryptococcosis patients, and the cryptococcal strains from these patients were reported as C. neoformans (three strains), C. gattii (one strain), and Cryptococcus (three strains not identified to the species level). We identified all three strains that had not been identified to the species level as C. gattii. Notably, the three strains that were reported as C. neoformans but were unavailable for species confirmation originated from Sothern California and Thailand where C. gattii is endemic. Most clinical laboratories designate C. neoformans without distinguishing between the two species; hence, these three strains could have been C. gattii. Since C. gattii infects more immunocompetent patients than C. neoformans, we pursued the possibility that this antibody may be more prevalent in patients infected with C. gattii than in those infected with C. neoformans. We screened the plasma of 20 healthy controls and 30 "immunocompetent" patients with cryptococcal meningoencephalitis from China and Australia (multiple ethnicities). Anti-GM-CSF autoantibodies were detected only in the plasma of seven patients infected by C. gattii and one healthy volunteer and in none infected by C. neoformans. While plasma from these C. gattii patients completely prevented GM-CSF-induced p-STAT5 in normal human peripheral blood mononuclear cells (PBMCs), plasma from one healthy volunteer positive for anti-GM-CSF autoantibodies caused only partial blockage. Our results suggest that anti-GM-CSF autoantibodies may predispose otherwise immunocompetent individuals to meningoencephalitis caused by C. gattii but not necessarily to that caused by C. neoformans.
IMPORTANCE Cryptococcal meningoencephalitis is the most serious central nervous system (CNS) infection caused by Cryptococcus neoformans or C. gattii. Cryptococcus primarily infects immunocopromised patients but is also sporadically encountered in otherwise "immunocompetent" patients with no known risk. In a recent study, anti-GM-CSF autoantibodies were detected in the plasma of seven otherwise immunocompetent patients with cryptococcal meningoencephalitis. Four of seven (57%) cryptococcal isolates from these patients were identified as C. gattii, while three strains were unavailable for species confirmation. We collected plasma from 30 otherwise healthy patients with CNS cryptococcosis in China and Australia (multiethnic) and analyzed the samples for the presence of anti-GM-CSF autoantibodies. The results suggest that anti-GM-CSF autoantibodies are a risk factor for CNS infection by C. gattii but not C. neoformans. GM-CSF may have a specific role in host defense against C. gattii, thereby elevating the importance of determining the level of anti-GM-CSF autoantibodies which can impact clinical management.
C1 [Saijo, Tomomi; Kwon-Chung, Kyung J.] NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Chen, Jianghan; Yi, Jin] Second Mil Med Univ, Changzheng Hosp, Dept Dermatol, Shanghai, Peoples R China.
[Chen, Jianghan; Yi, Jin] Second Mil Med Univ, Changzheng Hosp, Key Lab Med Mycol, Shanghai, Peoples R China.
[Chen, Sharon C. -A.; Sorrell, Tania C.] Univ Sydney, Westmead Hosp, Ctr Infect Dis & Microbiol, Westmead, NSW 2145, Australia.
[Chen, Sharon C. -A.; Sorrell, Tania C.] Univ Sydney, Marie Bashir Inst, Sydney, NSW 2006, Australia.
[Rosen, Lindsey B.; Holland, Steven M.; Browne, Sarah K.] NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Bennett, John E.] NIAID, 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.
EM JKCHUNG@niaid.nih.gov
FU Intramural Program of the National Institutes of Allergy and Infectious
Diseases, National Institutes of Health; Shanghai Committee of Science
and Technology, China [12410710000]
FX This study was funded by the Intramural Program of the National
Institutes of Allergy and Infectious Diseases, National Institutes of
Health, and the Shanghai Committee of Science and Technology, China,
2012 (grant number 12410710000).
NR 49
TC 22
Z9 22
U1 0
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2150-7511
J9 MBIO
JI mBio
PD MAR-APR
PY 2014
VL 5
IS 2
AR e00912-14
DI 10.1128/mBio.00912-14
PG 8
WC Microbiology
SC Microbiology
GA AH1XR
UT WOS:000335915600041
PM 24643864
ER
PT J
AU Joseph, P
Fourie, N
Abey, S
Reddy, S
Wang, D
Martino, A
Smyser, P
Rahim-Williams, B
Reed, D
Henderson, W
AF Joseph, Paule
Fourie, Nicolaas
Abey, Sarah
Reddy, Swarnalatha
Wang, Dan
Martino, Angelina
Smyser, Paul
Rahim-Williams, Bridgette
Reed, Danielle
Henderson, Wendy
TI Obesity Gene Expression Profile, Human Eating Behavior (HEB) and
Clinical Outcomes
SO NURSING RESEARCH
LA English
DT Meeting Abstract
C1 [Joseph, Paule] Univ Penn, Philadelphia, PA 19104 USA.
[Rahim-Williams, Bridgette] Natl Inst Minor Hlth & Hlth Dispar, Bethesda, MD USA.
[Reed, Danielle] Monell Chem Senses Ctr, Philadelphia, PA USA.
NR 0
TC 0
Z9 0
U1 2
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-6562
EI 1538-9847
J9 NURS RES
JI Nurs. Res.
PD MAR-APR
PY 2014
VL 63
IS 2
BP E95
EP E95
PG 1
WC Nursing
SC Nursing
GA AE6JP
UT WOS:000334098000263
ER
PT J
AU Kutney-Lee, A
Brennan, C
Meterko, M
Ersek, M
AF Kutney-Lee, Ann
Brennan, Caitlin
Meterko, Mark
Ersek, Mary
TI Organization of Nursing and Quality of Care for Veterans at the End of
Life
SO NURSING RESEARCH
LA English
DT Meeting Abstract
C1 [Kutney-Lee, Ann] Univ Penn, Philadelphia, PA 19104 USA.
[Brennan, Caitlin] NIH, Ctr Clin, Bethesda, MD USA.
[Meterko, Mark] VA Boston Healthcare Syst, Boston, MA USA.
[Ersek, Mary] Univ Penn, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-6562
EI 1538-9847
J9 NURS RES
JI Nurs. Res.
PD MAR-APR
PY 2014
VL 63
IS 2
BP E129
EP E129
PG 1
WC Nursing
SC Nursing
GA AE6JP
UT WOS:000334098000355
ER
PT J
AU Sherwin, L
AF Sherwin, LeeAnne
TI Illness Representation & Health-related Quality of Life in Adults with
Irritable Bowel Syndrome
SO NURSING RESEARCH
LA English
DT Meeting Abstract
C1 [Sherwin, LeeAnne] NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-6562
EI 1538-9847
J9 NURS RES
JI Nurs. Res.
PD MAR-APR
PY 2014
VL 63
IS 2
BP E83
EP E83
PG 1
WC Nursing
SC Nursing
GA AE6JP
UT WOS:000334098000232
ER
PT J
AU Grabowski, MK
Redd, AD
AF Grabowski, Mary K.
Redd, Andrew D.
TI Molecular tools for studying HIV transmission in sexual networks
SO CURRENT OPINION IN HIV AND AIDS
LA English
DT Review
DE HIV; linkage; phylogenetics
ID BAYESIAN PHYLOGENETIC INFERENCE; EVOLUTIONARY DYNAMICS; TYPE-1
TRANSMISSION; MAXIMUM-LIKELIHOOD; ERROR-CORRECTION; VIRAL SEQUENCES;
DNA-SEQUENCES; GENITAL-TRACT; EPIDEMIC; INFECTION
AB Purpose of review
Phylogenetics is frequently used for studies of population-based HIV transmission. The purpose of this review is to highlight the current utilities and limitations of phylogenetics in HIV epidemiological research from sample collection through to data analysis.
Recent findings
Studies of HIV phylogenies can provide critical information about HIV epidemics that are otherwise difficult to obtain through traditional study design such as transmission of drug-resistant virus, mixing between demographic groups, and rapidity of viral spread within populations. However, recent results from empirical and theoretical studies of HIV phylogenies challenge some of the key assumptions and interpretations from phylogenetic studies. Recent findings include lack of transmission bottlenecks in MSM and injection drug use epidemics, evidence for preferential transmission of HIV virus in heterosexual epidemics, and limited evidence that tree topologies correlate directly with underlying network structures. Other challenges include a lack of a standardized definition for a phylogenetic transmission cluster and biased or sparse sampling of HIV transmission networks.
Summary
Phylogenetics is an important tool for HIV research, and offers opportunities to understand critical aspects of the HIV epidemic. Like all epidemiological research, the methods used and interpretation of results from phylogenetic studies should be made cautiously with careful consideration.
C1 [Grabowski, Mary K.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Redd, Andrew D.] NIAID, Immunoregulat Lab, NIH, Baltimore, MD USA.
RP Grabowski, MK (reprint author), 851 N Wolfe St,Rangos Bldg Room 527, Baltimore, MD 21205 USA.
EM Aredd2@jhmi.edu
FU Johns Hopkins Bloomberg School of Public Health Sommer Scholarship;
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX M.K.G. is supported by the Johns Hopkins Bloomberg School of Public
Health Sommer Scholarship. A.D.R. is supported by the Division of
Intramural Research, National Institute of Allergy and Infectious
Diseases, National Institutes of Health. 'There are no conflicts of
interest.
NR 81
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U1 3
U2 15
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1746-630X
EI 1746-6318
J9 CURR OPIN HIV AIDS
JI Curr. Opin. HIV AIDS
PD MAR
PY 2014
VL 9
IS 2
BP 126
EP 133
DI 10.1097/COH.0000000000000040
PG 8
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA AC3EQ
UT WOS:000332398200005
PM 24384502
ER
PT J
AU Simmons, WK
Rapuano, KM
Ingeholm, JE
Avery, J
Kallman, S
Hall, KD
Martin, A
AF Simmons, W. Kyle
Rapuano, Kristina M.
Ingeholm, John E.
Avery, Jason
Kallman, Seth
Hall, Kevin D.
Martin, Alex
TI The ventral pallidum and orbitofrontal cortex support food pleasantness
inferences
SO BRAIN STRUCTURE & FUNCTION
LA English
DT Article
DE Food; Pleasure; Ventral pallidum; Orbitofrontal cortex
ID ORBITAL PREFRONTAL CORTEX; DECISION-MAKING; EATING BEHAVIOR; HEDONIC
REWARD; HUMAN AMYGDALA; WEIGHT STATUS; OBESITY; BRAIN; TASTE; ACTIVATION
AB Food advertisements often promote choices that are driven by inferences about the hedonic pleasures of eating a particular food. Given the individual and public health consequences of obesity, it is critical to address unanswered questions about the specific neural systems underlying these hedonic inferences. For example, although regions such as the orbitofrontal cortex (OFC) are frequently observed to respond more to pleasant food images than less hedonically pleasing stimuli, one important hedonic brain region in particular has largely remained conspicuously absent among human studies of hedonic response to food images. Based on rodent research demonstrating that activity in the ventral pallidum underlies the hedonic pleasures experienced upon eating food rewards, one might expect that activity in this important 'hedonic hotspot' might also track inferred food pleasantness. To date, however, no human studies have assessed this question. We thus asked human subjects to undergo fMRI and make item-by-item ratings of how pleasant it would be to eat particular visually perceived foods. Activity in the ventral pallidum was strongly modulated with pleasantness inferences. Additionally, activity within a region of the orbitofrontal cortex that tracks the pleasantness of tastes was also modulated with inferred pleasantness. Importantly, the reliability of these findings is demonstrated by their replication when we repeated the experiment at a new site with new subjects. These two experiments demonstrate that the ventral pallidum, in addition to the OFC, plays a central role in the moment-to-moment hedonic inferences that influence food-related decision-making.
C1 [Simmons, W. Kyle; Avery, Jason] Laureate Inst Brain Res, Tulsa, OK 74136 USA.
[Simmons, W. Kyle] Univ Tulsa, Fac Community Med, Tulsa, OK 74104 USA.
[Simmons, W. Kyle; Rapuano, Kristina M.; Ingeholm, John E.; Kallman, Seth; Martin, Alex] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
[Avery, Jason] Univ Tulsa, Dept Biol Sci, Tulsa, OK 74104 USA.
[Hall, Kevin D.] NIDDK, Lab Biol Modeling, Bethesda, MD 20892 USA.
RP Simmons, WK (reprint author), Laureate Inst Brain Res, 6655 South Yale Ave, Tulsa, OK 74136 USA.
EM wksimmons@laureateinstitute.org
RI Simmons, William/K-8925-2015
OI Simmons, William/0000-0002-0399-9003
FU National Institute of Mental Health (NIMH); National Institute of
Diabetes and Digestive and Kidney Diseases; NIMH [1K01MH096175-01];
Oklahoma Tobacco Research Center
FX This research supported by the Intramural Research Programs of the
National Institute of Mental Health (NIMH), and the National Institute
of Diabetes and Digestive and Kidney Diseases, as well as NIMH Grant
1K01MH096175-01 and an Oklahoma Tobacco Research Center grant to Kyle
Simmons. We would like to thank both Dr. Steve Gotts and Dr. Wayne
Drevets for helpful comments on this manuscript and research.
NR 58
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U1 4
U2 11
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1863-2653
EI 1863-2661
J9 BRAIN STRUCT FUNCT
JI Brain Struct. Funct.
PD MAR
PY 2014
VL 219
IS 2
BP 473
EP 483
DI 10.1007/s00429-013-0511-0
PG 11
WC Anatomy & Morphology; Neurosciences
SC Anatomy & Morphology; Neurosciences & Neurology
GA AG9KG
UT WOS:000335737500003
PM 23397317
ER
PT J
AU Prasad, V
Grady, C
AF Prasad, Vinay
Grady, Christine
TI The misguided ethics of crossover trials
SO CONTEMPORARY CLINICAL TRIALS
LA English
DT Article
DE Crossover; Ethics of clinical trials; Trial validity
ID RENAL-CELL CARCINOMA; EVEROLIMUS
AB Crossover is increasingly favored in trials of cancer therapies; even those that seek to establish the basic efficacy of novel drugs. Crossover is done in part for trial recruitment, but also out of a sense we argue that this ethical inclination that crossover is a preferred trial choice is misguided. In seeking to sate the desires of participants, we might undermine a trial's ability to answer a meaningful clinical question. When a trial is incapable of answering a question, it becomes unethical. Using a crossover strategy in oncology clinical trials can make trials less ethical, not more. Published by Elsevier Inc.
C1 [Prasad, Vinay] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Grady, Christine] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
RP Grady, C (reprint author), NIH, Dept Bioeth, Ctr Clin, 10 Ctr Dr Bldg 10-1C118, Bethesda, MD 20892 USA.
EM vinayak.prasad@nih.gov; CGrady@cc.nih.gov
FU Intramural NIH HHS [Z99 CL999999]
NR 13
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Z9 7
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1551-7144
EI 1559-2030
J9 CONTEMP CLIN TRIALS
JI Contemp. Clin. Trials
PD MAR
PY 2014
VL 37
IS 2
BP 167
EP 169
DI 10.1016/j.cct.2013.12.003
PG 3
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA AG7ZA
UT WOS:000335636100001
PM 24365533
ER
PT J
AU Amundsen, CL
Richter, HE
Menefee, S
Vasavada, S
Rahn, DD
Kenton, K
Harvie, HS
Wallace, D
Meikle, S
AF Amundsen, Cindy L.
Richter, Holly E.
Menefee, Shawn
Vasavada, Sandip
Rahn, David D.
Kenton, Kim
Harvie, Heidi S.
Wallace, Dennis
Meikle, Susie
TI The Refractory Overactive Bladder: Sacral NEuromodulation vs. BoTulinum
Toxin Assessment: ROSETTA trial
SO CONTEMPORARY CLINICAL TRIALS
LA English
DT Article
DE Urgency urinary incontinence; Sacral neuromodulation; Onabotulinum toxin
A
ID IDIOPATHIC DETRUSOR OVERACTIVITY; URINARY URGE INCONTINENCE;
PLACEBO-CONTROLLED TRIAL; A TOXIN; SUBUROTHELIAL INJECTION;
NERVE-STIMULATION; DOUBLE-BLIND; EFFICACY; QUESTIONNAIRE;
ANTICHOLINERGICS
AB We present the rationale for and design of a randomized, open-label, active-control trial comparing the effectiveness of 200 units of onabotulinum toxin A (Botox A (R)) versus sacral neuromodulation (InterStim (R)) therapy for refractory urgency urinary incontinence (UUI). The Refractory Overactive Bladder: Sacral NEuromodulation vs. BoTulinum Toxin Assessment (ROSETTA) trial compares changes in urgency urinary incontinence episodes over 6 months, as well as other lower urinary tract symptoms, adverse events and cost effectiveness in women receiving these two therapies. Eligible participants had previously attempted treatment with at least 2 medications and behavioral therapy. We discuss the importance of evaluating two very different interventions, the challenges related to recruitment, ethical considerations for two treatments with significantly different costs, follow-up assessments and cost effectiveness. The ROSETTA trial will provide information to healthcare providers regarding the technical attributes of these interventions as well as the efficacy and safety of these two interventions on other lower urinary tract and pelvic floor symptoms. Enrollment began in March, 2012 with anticipated end to recruitment in mid 2014. (c) 2014 Elsevier Inc. All rights reserved.
C1 [Amundsen, Cindy L.] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA.
[Richter, Holly E.] Univ Alabama Birmingham, Dept Obstet & Gynecol, Birmingham, AL 35294 USA.
[Menefee, Shawn] Kaiser Perrnanente San Diego, Dept Obstet & Gynecol, San Diego, CA USA.
[Vasavada, Sandip] Cleveland Clin, Dept Obstet & Gynecol, Cleveland, OH 44106 USA.
[Rahn, David D.] Univ Texas Southwestern, Dept Obstet & Gynecol, Dallas, TX USA.
[Kenton, Kim] Loyola Univ, Stritch Sch Med, Dept Obstet & Gynecol & Urol, Chicago, IL 60611 USA.
[Harvie, Heidi S.] Univ Penn, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA.
[Wallace, Dennis] RTI Int, Res Triangle Pk, NC USA.
[Meikle, Susie] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Contracept & Reprod Hlth Branch, Populat Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Amundsen, CL (reprint author), Duke Univ, Med Ctr, Dept Obstet & Gynecol, Div Urogynecol & Reconstruct Pelv Surg, DUMC 3192, Durham, NC 27710 USA.
EM cindy.amundsen@duke.edu
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [U10-HD041267, U10 HD041261, U10 HD054214, U10 HD054215, U10
HD054241, U10 HD041250, U10 HD069031, U10 HD069010]; NIH Office of
Research on Women's Health
FX Supported by grants from The Eunice Kennedy Shriver National Institute
of Child Health and Human Development (U10-HD041267, U10 HD041261, U10
HD054214, U10 HD054215, U10 HD054241, U10 HD041250, U10 HD069031, U10
HD069010) and the NIH Office of Research on Women's Health.
NR 37
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Z9 9
U1 1
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1551-7144
EI 1559-2030
J9 CONTEMP CLIN TRIALS
JI Contemp. Clin. Trials
PD MAR
PY 2014
VL 37
IS 2
BP 272
EP 283
DI 10.1016/j.cct2014.01.009
PG 12
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA AG7ZA
UT WOS:000335636100014
PM 24486637
ER
PT J
AU Hayes, RB
Geller, A
Churchill, L
Jolicoeur, D
Murray, DM
Shoben, A
David, SP
Adams, M
Okuyemi, K
Fauver, R
Gross, R
Leone, F
Xiao, R
Waugh, J
Crawford, S
Ockene, JK
AF Hayes, Rashelle B.
Geller, Alan
Churchill, Linda
Jolicoeur, Denise
Murray, David M.
Shoben, Abigail
David, Sean P.
Adams, Michael
Okuyemi, Kola
Fauver, Randy
Gross, Robin
Leone, Frank
Xiao, Rui
Waugh, Jonathan
Crawford, Sybil
Ockene, Judith K.
TI Teaching tobacco dependence treatment and counseling skills during
medical school: Rationale and design of the Medical Students helping
patients Quit tobacco (MSQuit) group randomized controlled trial
SO CONTEMPORARY CLINICAL TRIALS
LA English
DT Article
DE Tobacco dependence treatment and counseling; 5As; Medical school
education; Medical students; Tobacco control; Group randomized
controlled trial
ID ONE-MINUTE PRECEPTOR; SMOKING-CESSATION; UNITED-STATES; INTERVENTION;
PHYSICIANS; EDUCATION; SMOKERS; PERCEPTIONS; CURRICULUM; PROJECT
AB Introduction: Physician-delivered tobacco treatment using the 5As is clinically recommended, yet its use has been limited. Lack of adequate training and confidence to provide tobacco treatment is cited as leading reasons for limited 5A use. Tobacco dependence treatment training while in medical school is recommended, but is minimally provided. The MSQuit trial (Medical Students helping patients Quit tobacco) aims to determine if a multi-modal and theoretically-guided tobacco educational intervention will improve tobacco dependence treatment skills (i.e. 5As) among medical students.
Methods/design: 10 U.S. medical schools were pair-matched and randomized in a group-randomized controlled trial to evaluate whether a multi-modal educational (MME) 'intervention compared to traditional education (TE) will improve observed tobacco treatment skills. MME is primarily composed of TE approaches (i.e. didactics) plus a 1st year web-based course and preceptor-objective score on an Objective Structured Clinical Examination (OSCE) tobacco-counseling smoking case among 3rd year medical students from schools who implemented the MME or TE.
Discussion: MSQuit is the first randomized to evaluate whether a tobacco treatment educational intervention implemented during medical school will improve medical students' tobacco treatment skills. We hypothesize that the MME intervention will better prepare students in tobacco dependence treatment as measured by the OSCE. If a comprehensive tobacco treatment educational learning approach is effective, while also feasible and acceptable to implement, then medical schools may substantially influence skill development and use of the 5As among future physicians. (c) 2014 The Authors. Published by Elsevier Inc.
C1 [Hayes, Rashelle B.; Churchill, Linda; Jolicoeur, Denise; Xiao, Rui; Crawford, Sybil; Ockene, Judith K.] Univ Massachusetts, Sch Med, Div Prevent & Behav Med, Dept Med, Worcester, MA 01655 USA.
[Geller, Alan] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA.
[Murray, David M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD USA.
[Shoben, Abigail] Ohio State Univ, Coll Publ Hlth, Div Biostat, Columbus, OH 43210 USA.
[David, Sean P.; Fauver, Randy] Stanford Univ, Sch Med, Dept Med, Div Gen Med Disciplines,Ctr Educ & Res Family & C, Palo Alto, CA 94304 USA.
[Adams, Michael] Georgetown Univ Hosp, Dept Med, Div Gen Internal Med, Washington, DC USA.
[Okuyemi, Kola] Univ Minnesota, Sch Med, Dept Med, Minneapolis, MN 55455 USA.
[Gross, Robin] Georgetown Univ Hosp, Dept Med, Div Pulm Crit Care & Sleep Med, Washington, DC 20007 USA.
[Leone, Frank] Univ Penn, Perelman Sch Med, Div Pulm Allergy & Crit Care Med, Philadelphia, PA 19104 USA.
[Waugh, Jonathan] Univ Alabama Birmingham, UAB Lung Hlth Ctr, Dept Clin & Diagnost Sci, Birmingham, AL USA.
RP Hayes, RB (reprint author), Univ Massachusetts, Sch Med, 55 Lake Ave North, Worcester, MA 01655 USA.
EM rashelle.hayes@umassmed.edu; ageller@hsph.harvard.edu;
linda.churchill@umassmed.edu; denise.jolicoeur@umassmed.edu;
david.murray2@nih.gov; ashoben@cph.osu.edu; spdavid@stanford.edu;
adams@gunet.georgetown.edu; kokuyemi@umn.edu; rfauver@stanford.edu;
rlg4@gunet.georgetown.edu; frank.tleone@uphs.upenn.edu;
rui.xiao@umassmed.edu; waughj@uab.edu; sybil.crawford@umassmed.edu;
judith.ockene@umassmed.edu
OI David, Sean/0000-0002-4922-2603
FU NIH/NCI [5R01 CA 136888, 5R01CA136888S]
FX This work was supported by the NIH/NCI research grant 5R01 CA 136888 and
5R01CA136888S to Judith K. Ockene & Rashelle B. Hayes respectively. We
also acknowledge all school site Pls, research coordinators, academic
detailers, research assistants, support staff, as well as the
participating medical students and preceptors who have implemented and
participated in the study thus far.
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PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1551-7144
EI 1559-2030
J9 CONTEMP CLIN TRIALS
JI Contemp. Clin. Trials
PD MAR
PY 2014
VL 37
IS 2
BP 284
EP 293
DI 10.1016/j.cct.2014.01.008
PG 10
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA AG7ZA
UT WOS:000335636100015
PM 24486635
ER
PT J
AU Chew, EY
Clemons, TE
Bressler, SB
Elman, MJ
Danis, RP
Domalpally, A
Heier, JS
Kim, JE
Garfinkel, RA
AF Chew, Emily Y.
Clemons, Traci E.
Bressler, Susan B.
Elman, Michael J.
Danis, Ronald P.
Domalpally, Amitha
Heier, Jeffrey S.
Kim, Judy E.
Garfinkel, Richard A.
CA AREDS2 Home Study Res Grp
TI Randomized trial of the ForeseeHome monitoring device for early
detection of neovascular age-related macular degeneration. The HOme
Monitoring of the Eye (HOME) study design - HOME Study report number 1
SO CONTEMPORARY CLINICAL TRIALS
LA English
DT Article
DE Age-related macular degeneration; Controlled clinical trial;
Home-monitoring; Choroidal neovascularization; Best-corrected visual
acuity
ID FACTOR TRAP-EYE; VISUAL IMPAIRMENT; SUBGROUP ANALYSIS; UNITED-STATES;
RANIBIZUMAB; BEVACIZUMAB; PREVALENCE; MULTICENTER; ACUITY
AB Objective: To evaluate the effects of a home-monitoring device with tele-monitoring compared with standard care in detection of progression to choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD), the leading cause of blindness in the US. Patients and methods: Participants, aged 55 to 90 years, at high risk of developing CNV associated with AMD were recruited to the HOme Monitoring of Eye (HOME) Study, an unmasked, multi-center, randomized trial of the ForeseeHome (FH) device plus standard care vs. standard care alone. The FH device utilizes preferential hyperacuity perimetry and tele-monitoring to detect changes in vision function associated with development of CNV, potentially prior to symptom and visual acuity loss. After establishing baseline measurements, subsequent changes on follow-up are detected by the device, causing the monitoring center to alert the clinical center to recall participants for an exam. Standard care consists of instructions for self-monitoring visual changes with subsequent self-report to the clinical center. The primary objective of this study is to determine whether home monitoring plus standard care in comparison with standard care alone, results in earlier detection of incident CNV with better present visual acuity. The primary outcome is the decline in visual acuity at CNV diagnosis from baseline. Detection of CNV prior to substantial vision loss is critical as vision outcome following anti-angiogenic therapy is dependent on the visual acuity at initiation of treatment. Discussion: HOME Study is the first large scale study to test the use of home tele-monitoring system in the management of AMD patients. Published by Elsevier Inc.
C1 [Chew, Emily Y.] NEI, Bethesda, MD 20892 USA.
[Clemons, Traci E.] EMMES Corp, Rockville, MD USA.
[Bressler, Susan B.] Johns Hopkins Univ Hosp, Wilmer Eye Inst, Dept Ophthalmol, Baltimore, MD 21287 USA.
[Elman, Michael J.] Elman Retina Grp, Baltimore, MD USA.
[Danis, Ronald P.; Domalpally, Amitha] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Sch Med & Publ Hlth, Madison, WI 53706 USA.
[Heier, Jeffrey S.] Ophthalm Consultant Boston, Boston, MA USA.
[Kim, Judy E.] Med Coll Wisconsin, Dept Ophthalmol, Milwaukee, WI 53226 USA.
[Garfinkel, Richard A.] Retina Grp Washington, Bethesda, MD USA.
RP Chew, EY (reprint author), NIH, CRC, Bldg 10,Room 3-2531,10 Ctr Dr,MSC-1204, Bethesda, MD 20892 USA.
EM echew@nei.nih.gov
RI Domalpally, Amitha/B-2367-2015;
OI Heier, Jeffrey/0000-0003-4625-3145
FU Notal Vision through a clinical trial agreement with the NEI
[CTA-00833]; EMMES Corporation; National Eye Institute/National
Institutes of Health (NEI/NIH); Department of Health and Human Services,
Bethesda, MD [HHS-N-260-2005-00007-C]; ADB [N01-EY-5-0007]; Office of
Dietary Supplements (ODS); National Center for Complementary and
Alternative Medicine (NCCAM); National Institute on Aging (NIA);
National Heart, Lung and Blood Institute (NHLBI); National Institute of
Neurological Disorders and Stroke (N1NDS)
FX Financial support to the study was provided by the Notal Vision through
a clinical trial agreement with the NEI (CTA-00833) and a service
agreement with EMMES Corporation. The AREDS2 study is supported by the
intramural program funds and contracts from the National Eye
Institute/National Institutes of Health (NEI/NIH), Department of Health
and Human Services, Bethesda, MD. Contract No. HHS-N-260-2005-00007-C.
ADB Contract No. N01-EY-5-0007. Funds were generously contributed to
these contracts by the following NIH institutes: Office of Dietary
Supplements (ODS), National Center for Complementary and Alternative
Medicine (NCCAM), National Institute on Aging (NIA), National Heart,
Lung and Blood Institute (NHLBI), and National Institute of Neurological
Disorders and Stroke (N1NDS). The study medications and raw materials
were provided by Alcon, Bausch and Lomb, DSM, and Pfizer.
NR 19
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U1 1
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PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1551-7144
EI 1559-2030
J9 CONTEMP CLIN TRIALS
JI Contemp. Clin. Trials
PD MAR
PY 2014
VL 37
IS 2
BP 294
EP 300
DI 10.1016/j.cct.2014.02.003
PG 7
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA AG7ZA
UT WOS:000335636100016
PM 24530651
ER
PT J
AU Cochran, EK
Valentine, V
Samaan, KH
Corey, IB
Jackson, JA
AF Cochran, Elaine K.
Valentine, Virginia
Samaan, Karen H.
Corey, Ilene B.
Jackson, Jeffrey A.
TI Practice Tips and Tools for the Successful Use of U-500 Regular Human
Insulin The Diabetes Educator Is Key
SO DIABETES EDUCATOR
LA English
DT Article
ID CLINICAL-EXPERIENCE; GLYCEMIC CONTROL; GLUCOSE CONTROL; U-100 INSULIN;
THERAPY; MANAGEMENT; RESISTANCE; OBESE; HYPERGLYCEMIA; MELLITUS
AB This review provides information to equip diabetes educators to instruct and guide patients in using U-500 human regular insulin (U-500R). The article includes an overview of U-500R pharmacology and clinical data, strategies for outpatient and inpatient use, and tools for patient education. U-500R is useful for treating patients with any type of diabetes who require high doses of insulin. U-500R alleviates the volume-related problems associated with high doses of U-100 insulin, making treatment with high doses of insulin more feasible (because of the need for fewer injections for patients) as well as more cost-efficient and potentially more effective. These tools can help diabetes educators feel more comfortable and confident as they advise and educate patients who receive high-dose U-500R as part of their overall diabetes care plan. The diabetes educator plays a vital role in helping patients use U-500R safely and successfully.
C1 [Cochran, Elaine K.] NIDDK, NIH, Bethesda, MD 20892 USA.
[Valentine, Virginia] Diabet Network Inc, Albuquerque, NM USA.
[Samaan, Karen H.] St Vincents Hosp, Indianapolis, IN USA.
[Corey, Ilene B.; Jackson, Jeffrey A.] Lilly USA LLC, Indianapolis, IN USA.
RP Cochran, EK (reprint author), Natl Inst Diabet, NIH, 9000 Rockville Pike,10-CRC 6-5940, Bethesda, MD 20892 USA.
EM elainec@intra.niddk.nih.gov
NR 47
TC 5
Z9 5
U1 0
U2 2
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0145-7217
EI 1554-6063
J9 DIABETES EDUCATOR
JI Diabetes Educ.
PD MAR
PY 2014
VL 40
IS 2
BP 153
EP 165
DI 10.1177/0145721713508822
PG 13
WC Endocrinology & Metabolism; Public, Environmental & Occupational Health
SC Endocrinology & Metabolism; Public, Environmental & Occupational Health
GA AD3VE
UT WOS:000333173500001
PM 24159006
ER
PT J
AU Moshesh, M
Olshan, AF
Saldana, T
Baird, D
AF Moshesh, Malana
Olshan, Andrew F.
Saldana, Tina
Baird, Donna
TI Examining the Relationship Between Uterine Fibroids and Dyspareunia
Among Premenopausal Women in the United
SO JOURNAL OF SEXUAL MEDICINE
LA English
DT Article
DE Dyspareunia; Fibroids; Sexual Dysfunction; Pelvic Pain; Sexual Pain;
Pelvic Pathology
ID SEXUAL FUNCTION; PREVALENCE; LEIOMYOMA; PAIN; CHILDBIRTH; DELIVERY;
FEMALE; PREGNANCY; SYSTEM; HEALTH
AB IntroductionDespite estimates of a high prevalence of deep dyspareunia (DD) among women in the United States, risk factors for this important area of sexual dysfunction have been largely understudied.
AimsThe purpose of this study was to examine the relationship between uterine fibroids and the prevalence of DD.
MethodsWe used data from the Uterine Fibroid Study (enrollment 1996-1999 in a U.S. metropolitan area). Participating women were ages 35-49 and were randomly selected from the membership rolls of a prepaid health plan. Women were asked to provide detailed health information including a symptom questionnaire with questions about DD and to have a study ultrasound to screen for fibroids 0.5cm in diameter. The analysis included 827 women, after restriction to participants who were premenopausal with an intact uterus, sexually active, completed the symptom questionnaire, and had fibroid status adequately assessed. Logistic regression was conducted to estimate the adjusted prevalence odds ratio (aPOR) for the association of DD with presence of fibroids after adjusting for age, ethnicity, education, depression, physical activity, parity, and pelvic pathology.
Main Outcome MeasureOur main outcome measures were the presence and severity of DD.
ResultsThe presence of fibroids was significantly associated with DD (aPOR=1.7 95% confidence interval [CI] 1.1, 2.5). The aPOR was stronger for severe DD, DD that interfered with normal activity some or a lot (aPOR=3.1 95% CI 1.2, 8.2). However, there was not a significant dose response relationship between fibroid burden (measured by uterine volume) and DD. Fundal fibroids were more strongly associated with DD than other fibroids. Additional factors associated with significantly elevated odds of DD were parity, depression, younger age, and pelvic pathology.
ConclusionOur results suggest that fibroids are associated with DD. The association may not be causal but may reflect shared etiology and/or pathologic pathways. Moshesh M, Olshan AF, Saldana T, and Baird D. Examining the relationship between uterine fibroids and dyspareunia among premenopausal women in the US. J Sex Med 2014;11:800-808.
C1 [Moshesh, Malana; Baird, Donna] NIEHS, NIH, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
[Olshan, Andrew F.] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA.
[Saldana, Tina] Social & Sci Syst Inc, Durham, NC USA.
RP Baird, D (reprint author), NIEHS, Epidemiol Branch, A3-05,111 TW Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA.
EM baird@niehs.nih.gov
RI Baird, Donna/D-5214-2017
OI Baird, Donna/0000-0002-5544-2653
FU NIH; National Institute of Environmental Health Sciences
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Environmental Health Sciences. We would like
to acknowledge Drs. Nils-Halvdan Morken and Hazel Nichols who both
provided helpful comments on an earlier draft of the manuscript.
NR 29
TC 7
Z9 7
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1743-6095
EI 1743-6109
J9 J SEX MED
JI J. Sex. Med.
PD MAR
PY 2014
VL 11
IS 3
BP 800
EP 808
DI 10.1111/jsm.12425
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA AB9UD
UT WOS:000332140300017
PM 24467730
ER
PT J
AU Workman, TE
Fiszman, M
Rindflesch, TC
Nahl, D
AF Workman, T. Elizabeth
Fiszman, Marcelo
Rindflesch, Thomas C.
Nahl, Diane
TI Framing Serendipitous Information-Seeking Behavior for Facilitating
Literature-Based Discovery: A Proposed Model
SO JOURNAL OF THE ASSOCIATION FOR INFORMATION SCIENCE AND TECHNOLOGY
LA English
DT Article
ID FISH-OIL; GENERATING HYPOTHESES; SLEEP-DEPRIVATION; BIOMEDICAL TEXT;
KNOWLEDGE; RETRIEVAL; MAGNESIUM; FRAMEWORK; MIGRAINE; RAYNAUDS
AB Several researchers have studied serendipitous knowledge discovery in information-seeking behavior. Electronic data in the form of semantic predications have a potential role in literature-based discovery, which can be guided by serendipitous knowledge discovery research findings. We sought to model information-seeking behavior within the context of serendipitous knowledge discovery by leveraging existing research. These efforts were done with an eye for a potential literature-based discovery application that utilizes semantic predications. We performed a literature search, reviewed the results, and applied the findings in developing a model for serendipitous knowledge discovery as an information-seeking behavior. The literature review indicated four important themes in serendipitous knowledge discovery: iteration, change or clarification, a seeker's prior knowledge, and the role of information organization and presentation. The Interaction Flow in Serendipitous Knowledge Discovery (IF-SKD) model includes these themes, and accommodates iterative, evolving search interests. Output can be presented in a manner to enhance short-term memory conceptualization and connections with prior knowledge. Although the IF-SKD model is currently a theoretical structure, its utility is demonstrated through replicating a literature-based discovery event, using a documented search method within the model's steps. The IF-SKD model can potentially serve as the foundation for future literature-based discovery applications.
C1 [Workman, T. Elizabeth; Fiszman, Marcelo; Rindflesch, Thomas C.] Natl Lib Med, Lister Hill Ctr, Bethesda, MD 20894 USA.
[Nahl, Diane] Univ Hawaii, Dept Informat & Comp Sci, Lib & Informat Sci Program, Hamilton Lib 3C, Honolulu, HI 96822 USA.
RP Workman, TE (reprint author), Natl Lib Med, Lister Hill Ctr, 8600 Rockville Pike,Bldg 38A,Room B1N30A4, Bethesda, MD 20894 USA.
EM workmante@mail.nih.gov; fiszmanm@mail.nih.gov; tcr@nlm.nih.gov;
nahl@hawaii.edu
FU National Institutes of Health, National Library of Medicine; National
Library of Medicine
FX This study was supported in part by the Intramural Research Program of
the National Institutes of Health, National Library of Medicine. This
research was supported in part by an appointment of the first author to
the Lister Hill Center Fellows Program sponsored by the National Library
of Medicine and administered by the Oak Ridge Institute for Science and
Education.
NR 73
TC 3
Z9 3
U1 3
U2 32
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2330-1635
EI 2330-1643
J9 J ASSOC INF SCI TECH
PD MAR
PY 2014
VL 65
IS 3
BP 501
EP 512
DI 10.1002/asi.22999
PG 12
WC Computer Science, Information Systems; Information Science & Library
Science
SC Computer Science; Information Science & Library Science
GA AG7EZ
UT WOS:000335582300005
ER
PT J
AU Kahn, MG
Bailey, LC
Forrest, CB
Padula, MA
Hirschfeld, S
AF Kahn, Michael G.
Bailey, L. Charles
Forrest, Christopher B.
Padula, Michael A.
Hirschfeld, Steven
TI Building a Common Pediatric Research Terminology for Accelerating Child
Health Research
SO PEDIATRICS
LA English
DT Review
DE terminology harmonization; clinical research; learning health system;
governance; pediatric research; ontology
ID EFFECTIVENESS RESEARCH CER; INHALED NITRIC-OXIDE; CLINICAL-RESEARCH;
INTERNATIONAL CLASSIFICATION; RESPIRATORY-FAILURE; BIOMEDICAL ONTOLOGY;
NATIONAL CENTER; DATA STANDARDS; EDM-FORUM; QUALITY
AB Longitudinal observational clinical data on pediatric patients in electronic format is becoming widely available. A new era of multi-institutional data networks that study pediatric diseases and outcomes across disparate health delivery models and care settings are also enabling an innovative collaborative rapid improvement paradigm called the Learning Health System. However, the potential alignment of routine clinical care, observational clinical research, pragmatic clinical trials, and health systems improvement requires a data infrastructure capable of combining information from systems and workflows that historically have been isolated from each other. Removing barriers to integrating and reusing data collected in different settings will permit new opportunities to develop a more complete picture of a patient's care and to leverage data from related research studies. One key barrier is the lack of a common terminology that provides uniform definitions and descriptions of clinical observations and data. A well-characterized terminology ensures a common meaning and supports data reuse and integration. A common terminology allows studies to build upon previous findings and to reuse data collection tools and data management processes. We present the current state of terminology harmonization and describe a governance structure and mechanism for coordinating the development of a common pediatric research terminology that links to clinical terminologies and can be used to align existing terminologies. By reducing the barriers between clinical care and clinical research, a Learning Health System can leverage and reuse not only its own data resources but also broader extant data resources.
C1 [Kahn, Michael G.] Univ Colorado, Dept Pediat, Aurora, CO 80045 USA.
[Bailey, L. Charles; Forrest, Christopher B.; Padula, Michael A.] Univ Penn, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Bailey, L. Charles; Forrest, Christopher B.; Padula, Michael A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Hirschfeld, Steven] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Kahn, MG (reprint author), Univ Colorado, Dept Pediat, Childrens Hosp Colorado, 13123 E 16th Ave,B400, Aurora, CO 80045 USA.
EM michael.kahn@childrenscolorado.org
RI Hirschfeld, Steven/E-2987-2016;
OI Hirschfeld, Steven/0000-0003-0627-7249; Padula,
Michael/0000-0003-2050-5930
FU National Children's Study [HHSN275200800018C, HHSN267200700020C];
National Institutes of Health, National Center for Advancing
Translational Sciences, Colorado Clinical and Translational Sciences
Institute [UL1 TR000154]; Agency for Healthcare Research Quality
[R01HS020024-03]; National Institutes of Health (NIH)
FX Supported by National Children's Study contracts HHSN275200800018C (to
Dr Kahn) and HHSN267200700020C (to Drs Bailey, Forrest, and Padula);
National Institutes of Health, National Center for Advancing
Translational Sciences, Colorado Clinical and Translational Sciences
Institute grant UL1 TR000154 to Dr Kahn and Agency for Healthcare
Research & Quality R01HS020024-03 (to Drs Bailey and Forrest). Funded by
the National Institutes of Health (NIH).
NR 54
TC 13
Z9 15
U1 2
U2 6
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
EI 1098-4275
J9 PEDIATRICS
JI Pediatrics
PD MAR
PY 2014
VL 133
IS 3
BP 516
EP 525
DI 10.1542/peds.2013-1504
PG 10
WC Pediatrics
SC Pediatrics
GA AG3PB
UT WOS:000335330700024
PM 24534404
ER
PT J
AU Frattarelli, DAC
Galinkin, JL
Green, TP
Johnson, TD
Neville, KA
Paul, IM
Van den Anker, JN
Knight, M
Alexander, JJ
Kilpatrick, SJ
Cragan, JD
Rieder, MJ
Robb, AS
Sachs, H
Zajicek, A
Haro, T
Koteras, RK
Del Monte, M
AF Frattarelli, Daniel A. C.
Galinkin, Jeffrey L.
Green, Thomas P.
Johnson, Timothy D.
Neville, Kathleen A.
Paul, Ian M.
Van den Anker, John N.
Knight, Matthew
Alexander, John J.
Kilpatrick, Sarah J.
Cragan, Janet D.
Rieder, Michael J.
Robb, Adelaide S.
Sachs, Hari
Zajicek, Anne
Haro, Tamar
Koteras, Raymond K.
Del Monte, Mark
CA COMM DRUGS
TI Off-Label Use of Drugs in Children
SO PEDIATRICS
LA English
DT Article
DE off-label drug use; pharmaceuticals; pediatrics; infants; children;
adolescents; prescribing
AB The passage of the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act has collectively resulted in an improvement in rational prescribing for children, including more than 500 labeling changes. However, off-label drug use remains an important public health issue for infants, children, and adolescents, because an overwhelming number of drugs still have no information in the labeling for use in pediatrics. The purpose of off-label use is to benefit the individual patient. Practitioners use their professional judgment to determine these uses. As such, the term off-label does not imply an improper, illegal, contraindicated, or investigational use. Therapeutic decision-making must always rely on the best available evidence and the importance of the benefit for the individual patient.
C1 [Alexander, John J.; Sachs, Hari] US FDA, Rockville, MD 20857 USA.
[Kilpatrick, Sarah J.] Amer Coll Obstetricians & Gynecologists, Washington, DC USA.
[Cragan, Janet D.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Rieder, Michael J.] Canadian Pediat Soc, Ottawa, ON, Canada.
[Robb, Adelaide S.] Amer Acad Child & Adolescent Psychiat, Washington, DC USA.
[Zajicek, Anne] NIH, Bethesda, MD USA.
OI Paul, Ian/0000-0002-6344-8609
NR 7
TC 48
Z9 52
U1 0
U2 7
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
EI 1098-4275
J9 PEDIATRICS
JI Pediatrics
PD MAR
PY 2014
VL 133
IS 3
BP 563
EP 567
DI 10.1542/peds.2013-4060
PG 5
WC Pediatrics
SC Pediatrics
GA AG3PB
UT WOS:000335330700036
PM 24567009
ER
PT J
AU Lei, EP
AF Lei, Elissa P.
TI Special Issue: Chromatin and epigenetic regulation of animal development
Preface
SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
LA English
DT Editorial Material
C1 Natl Inst Diabet & Digest & Kidney Dis, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA.
RP Lei, EP (reprint author), Natl Inst Diabet & Digest & Kidney Dis, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1874-9399
EI 0006-3002
J9 BBA-GENE REGUL MECH
JI Biochim. Biophys. Acta-Gene Regul. Mech.
PD MAR
PY 2014
VL 1839
IS 3
SI SI
BP 117
EP 117
DI 10.1016/j.bbagrm.2014.02.003
PG 1
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA AE3MX
UT WOS:000333881700001
PM 24530644
ER
PT J
AU Matzat, LH
Lei, EP
AF Matzat, Leah H.
Lei, Elissa P.
TI Surviving an identity crisis: A revised view of chromatin insulators in
the genomics era
SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
LA English
DT Review
DE Chromatin; Insulator; Nuclear organization; Drosophila
ID DROSOPHILA-BITHORAX COMPLEX; HAIRY-WING PROTEIN; POSITION-EFFECT
VARIEGATION; ENHANCER-BLOCKING ACTIVITY; CIS-REGULATORY DOMAINS;
RESPONSE ELEMENT PRE; ZINC-FINGER PROTEIN; DNA-BINDING DOMAIN; ACTIVE
PROMOTERS; GYPSY INSULATOR
AB The control of complex, developmentally regulated loci and partitioning of the genome into active and silent domains is in part accomplished through the activity of DNA-protein complexes termed chromatin insulators. Together, the multiple, well-studied classes of insulators in Drosophila melanogaster appear to be generally functionally conserved. In this review, we discuss recent genomic-scale experiments and attempt to reconcile these newer findings in the context of previously defined insulator characteristics based on classical genetic analyses and transgenic approaches. Finally, we discuss the emerging understanding of mechanisms of chromatin insulator regulation. This article is part of a Special Issue entitled: Chromatin and epigenetic regulation of animal development. Published by Elsevier B.V.
C1 [Matzat, Leah H.; Lei, Elissa P.] Natl Inst Diabet & Digest & Kidney Dis, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Lei, EP (reprint author), 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM leielissa@niddk.nih.gov
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases
FX We would like to thank S. Henikoff and V. Studitsky for discussion of
the chromatin flexibility concept. We are also grateful to R. Dale, A.
Dean, J. Kassis, and members of the Lei laboratory for comments on the
manuscript This work was funded by the Intramural Research Program of
the National Institute of Diabetes and Digestive and Kidney Diseases.
NR 152
TC 16
Z9 16
U1 0
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1874-9399
EI 0006-3002
J9 BBA-GENE REGUL MECH
JI Biochim. Biophys. Acta-Gene Regul. Mech.
PD MAR
PY 2014
VL 1839
IS 3
SI SI
BP 203
EP 214
DI 10.1016/j.bbagrm.2013.10.007
PG 12
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA AE3MX
UT WOS:000333881700009
PM 24189492
ER
PT J
AU Isbrucker, R
Arciniega, J
McFarland, R
Chapsal, JM
Xing, D
Bache, C
Nelson, S
Costanzo, A
Hoonakker, M
Castiaux, A
Halder, M
Casey, W
Johnson, N
Jones, B
Doelling, V
Sprankle, C
Rinckel, L
Stokes, W
AF Isbrucker, Richard
Arciniega, Juan
McFarland, Richard
Chapsal, Jean-Michel
Xing, Dorothy
Bache, Christina
Nelson, Sue
Costanzo, Angele
Hoonakker, Marieke
Castiaux, Amelie
Halder, Marlies
Casey, Warren
Johnson, Nelson
Jones, Brett
Doelling, Vivian
Sprankle, Cathy
Rinckel, Lori
Stokes, William
TI Report on the international workshop on alternatives to the murine
histamine sensitization test (HIST) for acellular pertussis vaccines:
State of the science and the path forward
SO BIOLOGICALS
LA English
DT Article
DE Pertussis toxin; Acellular pertussis vaccines; Alternative methods;
Safety; Biochemical assays; Cell-based assays
ID TOXIN; ASSAY; STRATEGIES
AB Regulatory authorities require safety and potency testing prior to the release of each production lot of acellular pertussis (aP)-containing vaccines. Currently, the murine histamine sensitization test (HIST) is used to evaluate the presence of residual pertussis toxin in aP containing vaccines. However, the testing requires the use of a significant number of mice and results in unrelieved pain and distress. NICEATM, ICCVAM, their partners in the International Cooperation on Alternative Test Methods, and the International Working Group for Alternatives to HIST organized a workshop to discuss recent developments in alternative assays to the HIST, review data from an international collaborative study on non-animal alternative tests that might replace the HIST, and address the path toward global acceptance of this type of method. Currently, there are three potential alternative methods to HIST. Participants agreed that no single in vitro method was sufficiently developed for harmonized validation studies at this time. It is unlikely that any single in vitro method would be applicable to all aP vaccines without modification, due to differences between vaccines. Workshop participants recommended further optimization of cell-based assays under development. Participants agreed that the next international collaborative studies should commence in 2013 based on discussions during this workshop.
C1 [Isbrucker, Richard] Hlth Canada, Biol & Genet Therapies Directorate, Ottawa, ON K1A 0K9, Canada.
[Arciniega, Juan; McFarland, Richard] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA.
[Chapsal, Jean-Michel] Sanofi Pasteur, Lyon, France.
[Xing, Dorothy] Natl Inst Biol Stand & Controls, Div Bacteriol, S Mimms EN6 3QG, Herts, England.
[Bache, Christina] Paul Ehrlich Inst, D-63225 Langen, Germany.
[Nelson, Sue] Sanofi Pasteur, Toronto, ON, Canada.
[Costanzo, Angele] European Directorate Qual Med & Healthcare, Strasbourg, France.
[Hoonakker, Marieke] Netherlands Vaccine Inst, NL-3721 MA Bilthoven, Netherlands.
[Castiaux, Amelie] GlaxoSmithKline, B-1330 Rixensart, Belgium.
[Halder, Marlies] Inst Hlth & Consumer Protect, European Commiss Joint Res Ctr, European Union Reference Lab Alternat Anim Testin, I-21027 Ispra, Varese, Italy.
[Casey, Warren; Stokes, William] Natl Inst Environm Hlth Sci, Natl Toxicol Program, Ctr Evaluat, Alternat Toxicol Methods Div,NIH, Res Triangle Pk, NC 27709 USA.
[Johnson, Nelson; Jones, Brett; Doelling, Vivian; Sprankle, Cathy; Rinckel, Lori; Stokes, William] Integrated Lab Syst Inc, Morrisville, NC 27560 USA.
RP Isbrucker, R (reprint author), Hlth Canada, Biol & Genet Therapies Directorate, 100 Eglantine Dr, Ottawa, ON K1A 0K9, Canada.
EM richard.isbrucker@hc-sc.gc.ca
FU NICEATM; ICCVAM; EURL ECVAM; JaCVAM; International Cooperation on
Alternative Test Methods
FX The authors extend their sincere appreciation to all participants in the
international workshop for their contributions leading to the workshop
conclusions and recommendations. The members of the HIST Workshop
Organizing Committee, the International Working Group for Alternatives
to HIST, ICCVAM Interagency Biologics Working Group, and NICEATM staff
are acknowledged for their contributions to the planning of the
workshop. All of the invited experts are acknowledged for their
contributions to roundtable discussions and workshop proceedings.
Participating national and international validation organizations from
the International Cooperation on Alternative Test Methods, including
NICEATM, ICCVAM, EURL ECVAM, and JaCVAM, are gratefully acknowledged for
their scientific contributions and financial support. Finally, the
authors gratefully acknowledge Dr. Raymond Tice and Dr. John Bucher from
the National Institute of Environmental Health Sciences, National
Institutes of Health, USA, for their review of the manuscript.
NR 20
TC 0
Z9 0
U1 2
U2 6
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1045-1056
EI 1095-8320
J9 BIOLOGICALS
JI Biologicals
PD MAR
PY 2014
VL 42
IS 2
BP 114
EP 122
DI 10.1016/j.biologicals.2013.11.011
PG 9
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Pharmacology & Pharmacy
GA AG1UR
UT WOS:000335202200008
PM 24394373
ER
PT J
AU Calderon, B
Sacks, DB
AF Calderon, Boris
Sacks, David B.
TI Islet Autoantibodies and Type 1 Diabetes: Does the Evidence Support
Screening?
SO CLINICAL CHEMISTRY
LA English
DT Editorial Material
C1 [Calderon, Boris] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
[Sacks, David B.] NIH, Dept Lab Med, Bethesda, MD 20892 USA.
RP Calderon, B (reprint author), Washington Univ, Sch Med, Dept Pathol & Immunol, 660 South Euclid Ave, St Louis, MO 63110 USA.
EM calderon@wustl.edu; sacksdb@mail.nih.gov
OI Calderon, Boris/0000-0003-1575-0739; Sacks, David/0000-0003-3100-0735
NR 5
TC 1
Z9 1
U1 0
U2 1
PU AMER ASSOC CLINICAL CHEMISTRY
PI WASHINGTON
PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA
SN 0009-9147
EI 1530-8561
J9 CLIN CHEM
JI Clin. Chem.
PD MAR
PY 2014
VL 60
IS 3
BP 438
EP 440
DI 10.1373/clinchem.2013.212381
PG 3
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA AG1AI
UT WOS:000335146800003
PM 24363370
ER
PT J
AU Knutson, KM
Dal Monte, O
Raymont, V
Wassermann, EM
Krueger, F
Grafman, J
AF Knutson, Kristine M.
Dal Monte, Olga
Raymont, Vanessa
Wassermann, Eric M.
Krueger, Frank
Grafman, Jordan
TI Neural correlates of apathy revealed by lesion mapping in participants
with traumatic brain injuries
SO HUMAN BRAIN MAPPING
LA English
DT Article
DE voxel-based lesion-symptom mapping; apathy; cingulate cortex; fatigue;
traumatic brain injury; insula
ID PENETRATING HEAD-INJURY; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE;
NEUROPSYCHIATRIC INVENTORY; ORBITOFRONTAL CORTEX; MULTIPLE-SCLEROSIS;
COGNITIVE FATIGUE; FUNCTIONAL MRI; RATING-SCALE; DEPRESSION
AB Apathy, common in neurological disorders, is defined as disinterest and loss of motivation, with a reduction in self-initiated activity. Research in diseased populations has shown that apathy is associated with variations in the volume of brain regions such as the anterior cingulate and the frontal lobes. The goal of this study was to determine the neural signatures of apathy in people with penetrating traumatic brain injuries (pTBIs), as to our knowledge, these have not been studied in this sample. We studied 176 male Vietnam War veterans with pTBIs using voxel-based lesion-symptom mapping (VLSM) and apathy scores from the UCLA Neuropsychiatric Inventory (NPI), a structured inventory of symptoms completed by a caregiver. Our results revealed that increased apathy symptoms were associated with brain damage in limbic and cortical areas of the left hemisphere including the anterior cingulate, inferior, middle, and superior frontal regions, insula, and supplementary motor area. Our results are consistent with the literature, and extend them to people with focal pTBI. Apathy is a significant symptom since it can reduce participation of the patient in family and other social interactions, and diminish affective decision-making. Hum Brain Mapp 35:943-953, 2014. (c) 2013 Wiley Periodicals, Inc.
C1 [Knutson, Kristine M.; Dal Monte, Olga; Wassermann, Eric M.] NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA.
[Dal Monte, Olga] Univ Turin, Dept Neuropsychol, Turin, Italy.
[Dal Monte, Olga] Henry M Jackson Fdn, Rockville, MD USA.
[Raymont, Vanessa] Univ London Imperial Coll Sci Technol & Med, Dept Med, London, England.
[Raymont, Vanessa] Johns Hopkins Univ, Dept Radiol, Baltimore, MD USA.
[Krueger, Frank] George Mason Univ, Mol Neurosci Dept, Fairfax, VA 22030 USA.
[Krueger, Frank] George Mason Univ, Dept Psychol, Fairfax, VA 22030 USA.
[Grafman, Jordan] Rehabil Inst Chicago, Brain Injury Res Program, Chicago, IL 60611 USA.
RP Grafman, J (reprint author), Rehabil Inst Chicago, Brain Injury Res Program, 345 East Super St, Chicago, IL 60611 USA.
EM fkrueger@gmu.edu; jgrafman@ric.org
OI Grafman, Jordan H./0000-0001-8645-4457; dal monte,
olga/0000-0002-7823-4769; Knutson, Kristine/0000-0003-4626-4514
FU U.S. National Institute of Neurological Disorders and Stroke; United
States Army Medical Research and Material Command [DAMD17-01-1-0675]
FX This work was supported by funding from the U.S. National Institute of
Neurological Disorders and Stroke intramural research program and a
project grant from the United States Army Medical Research and Material
Command administered by the Henry M. Jackson Foundation (Vietnam Head
Injury Study Phase III: a 30-year post-injury follow-up study, grant
number DAMD17-01-1-0675).
NR 75
TC 10
Z9 10
U1 0
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1065-9471
EI 1097-0193
J9 HUM BRAIN MAPP
JI Hum. Brain Mapp.
PD MAR
PY 2014
VL 35
IS 3
BP 943
EP 953
DI 10.1002/hbm.22225
PG 11
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA AF0IW
UT WOS:000334398500016
PM 23404730
ER
PT J
AU Konig, G
Pickard, FC
Mei, Y
Brooks, BR
AF Koenig, Gerhard
Pickard, Frank C.
Mei, Ye
Brooks, Bernard R.
TI Predicting hydration free energies with a hybrid QM/MM approach: an
evaluation of implicit and explicit solvation models in SAMPL4
SO JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN
LA English
DT Article
DE Hydration free energy calculations; Non-Boltzmann Bennett; Implicit
solvent; Explicit solvent; QM/MM
ID PARTIAL ATOMIC CHARGES; GENERAL FORCE-FIELD; BLIND PREDICTION; DENSITY
FUNCTIONALS; BINDING AFFINITIES; AMINO-ACIDS; CHALLENGE; CHARMM;
SIMULATIONS; CHEMISTRY
AB The correct representation of solute-water interactions is essential for the accurate simulation of most biological phenomena. Several highly accurate quantum methods are available to deal with solvation by using both implicit and explicit solvents. So far, however, most evaluations of those methods were based on a single conformation, which neglects solute entropy. Here, we present the first test of a novel approach to determine hydration free energies that uses molecular mechanics (MM) to sample phase space and quantum mechanics (QM) to evaluate the potential energies. Free energies are determined by using re-weighting with the Non-Boltzmann Bennett (NBB) method. In this context, the method is referred to as QM-NBB. Based on snapshots from MM sampling and accounting for their correct Boltzmann weight, it is possible to obtain hydration free energies that incorporate the effect of solute entropy. We evaluate the performance of several QM implicit solvent models, as well as explicit solvent QM/MM for the blind subset of the SAMPL4 hydration free energy challenge. While classical free energy simulations with molecular dynamics give root mean square deviations (RMSD) of 2.8 and 2.3 kcal/mol, the hybrid approach yields an improved RMSD of 1.6 kcal/mol. By selecting an appropriate functional and basis set, the RMSD can be reduced to 1 kcal/mol for calculations based on a single conformation. Results for a selected set of challenging molecules imply that this RMSD can be further reduced by using NBB to reweight MM trajectories with the SMD implicit solvent model.
C1 [Koenig, Gerhard; Pickard, Frank C.; Mei, Ye; Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Rockville, MD 20852 USA.
[Mei, Ye] E China Normal Univ, Inst Theoret & Computat Sci, State Key Lab Precis Spect, Shanghai 200062, Peoples R China.
RP Konig, G (reprint author), NHLBI, Lab Computat Biol, NIH, 5635 Fishers Lane,T-900 Suite, Rockville, MD 20852 USA.
EM gerhard.koenig@nih.gov
RI MEI, Ye/C-5843-2009
OI MEI, Ye/0000-0002-3953-8508
FU National Heart, Lung and Blood Institute of the National Institutes of
Health
FX The authors would like to thank Tim Miller, Richard Venable and John
Legato for technical assistance with the parallelization of the QM/MM
calculations. The support by Yihan Shao was invaluable during the setup
of the Q-Chem scripts and we also would like to thank Florentina
Tofoleanu, Tim Miller and Juyong Lee for carefully reading and
commenting on the manuscript as well as Stefan Boresch and Lee Woodcock
for fruitful discussions on the optimal performance of NBB. This work
was supported by the intramural research program of the National Heart,
Lung and Blood Institute of the National Institutes of Health and
utilized the high-performance computational capabilities of the LoBoS
and Biowulf Linux clusters at the National Institutes of Health.
(http://www.lobos.nih.gov and http://biowulf.nih.gov).
NR 52
TC 25
Z9 25
U1 5
U2 35
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0920-654X
EI 1573-4951
J9 J COMPUT AID MOL DES
JI J. Comput.-Aided Mol. Des.
PD MAR
PY 2014
VL 28
IS 3
SI SI
BP 245
EP 257
DI 10.1007/s10822-014-9708-4
PG 13
WC Biochemistry & Molecular Biology; Biophysics; Computer Science,
Interdisciplinary Applications
SC Biochemistry & Molecular Biology; Biophysics; Computer Science
GA AG2GA
UT WOS:000335233100010
PM 24504703
ER
PT J
AU Taber, DR
Pratt, C
Charneco, EY
Dowda, M
Phillips, JA
Going, SB
AF Taber, Daniel R.
Pratt, Charlotte
Charneco, Eileen Y.
Dowda, Marsha
Phillips, Jennie A.
Going, Scott B.
TI Participation in Vigorous Sports, Not Moderate Sports, Is Positively
Associated With Cardiorespiratory Fitness Among Adolescent Girls
SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH
LA English
DT Article
DE vigorous activity; moderate activity; intervention
ID RANDOMIZED CONTROLLED-TRIAL; ALL-CAUSE MORTALITY; PHYSICAL-ACTIVITY;
CANCER-MORTALITY; UNITED-STATES; MEN; YOUTH; HEALTH; CHILDREN;
INTENSITIES
AB Background: There is controversy regarding whether moderately-intense sports can improve physical fitness, which declines throughout adolescence among girls. The objective was to estimate the association between moderate and vigorous sports participation and cardiorespiratory fitness in a racially diverse sample of adolescent girls. Methods: Cardiorespiratory fitness was measured using a modified physical work capacity test in 1029 eighth-grade girls participating in the Trial of Activity for Adolescent Girls. Girls reported sports in which they participated in the last year on an organized activity questionnaire. Using general linear mixed models, the study regressed absolute and relative fitness on the number of vigorous and moderate sports in which girls participated, race/ethnicity, age, treatment group, fat mass, fat-free mass, and an interaction between race and fat-free mass. Results: The number of vigorous sports in which girls participated was positively associated with absolute fitness (beta = 10.20, P = .04) and relative fitness (beta = 0.17, P = .04). Associations were reduced, but not eliminated, after controlling for MET-weighted MVPA. Participation in moderate sports was not associated with either fitness measure. Conclusions: Vigorous sports participation is positively associated with cardiorespiratory fitness. Future longitudinal research should analyze whether promoting vigorous sports at an early age can prevent age-related declines in cardiorespiratory fitness among adolescent girls.
C1 [Taber, Daniel R.] Univ Illinois, Inst Hlth Res & Policy, Chicago, IL 60607 USA.
[Pratt, Charlotte] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Charneco, Eileen Y.] Univ Puerto Rico, Sch Publ Hlth, San Juan, PR 00936 USA.
[Dowda, Marsha] Univ S Carolina, Dept Exercise Sci, Columbia, SC 29208 USA.
[Phillips, Jennie A.] Univ Maryland, Dept Kinesiol, College Pk, MD 20742 USA.
[Going, Scott B.] Univ Arizona, Dept Physiol, Tucson, AZ USA.
RP Taber, DR (reprint author), Univ Illinois, Inst Hlth Res & Policy, Chicago, IL 60607 USA.
FU NHLBI NIH HHS [U01HL066858, U01HL066852, U01 HL066853, U01 HL066857,
U01HL066855, U01HL066856, U01HL066853, U01 HL066845, U01HL066845, U01
HL066856, U01 HL066858, U01 HL066852, U01 HL066855, U01HL066857]
NR 44
TC 0
Z9 0
U1 0
U2 0
PU HUMAN KINETICS PUBL INC
PI CHAMPAIGN
PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA
SN 1543-3080
EI 1543-5474
J9 J PHYS ACT HEALTH
JI J. Phys. Act. Health
PD MAR
PY 2014
VL 11
IS 3
BP 596
EP 603
DI 10.1123/jpah.2011-0280
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AF8RQ
UT WOS:000334983700019
PM 23493300
ER
PT J
AU Van Domelen, DR
Caserotti, P
Brychta, RJ
Harris, TB
Patel, KV
Chen, KY
Arnardottir, NY
Eirikdottir, G
Launer, LJ
Gudnason, V
Sveinsson, T
Johannsson, E
Koster, A
AF Van Domelen, Dane R.
Caserotti, Paolo
Brychta, Robert J.
Harris, Tamara B.
Patel, Kushang V.
Chen, Kong Y.
Arnardottir, Nanna Yr
Eirikdottir, Gudny
Launer, Lenore J.
Gudnason, Vilmundur
Sveinsson, Thorarinn
Johannsson, Erlingur
Koster, Annemarie
TI Is There a Sex Difference in Accelerometer Counts During Walking in
Older Adults?
SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH
LA English
DT Article
DE physical activity; 6-minute walk test; accelerometry; AGES-Reykjavik
Study
ID INTENSITY PHYSICAL-ACTIVITY; ENERGY-EXPENDITURE; GENDER-DIFFERENCES;
ACTIVITY MONITORS; UNITED-STATES; SPEED; BALANCE; GAIT; HIP; AGE
AB Background: Accelerometers have emerged as a useful tool for measuring free-living physical activity in epidemiological studies. Validity of activity estimates depends on the assumption that measurements are equivalent for males and females while performing activities of the same intensity. The primary purpose of this study was to compare accelerometer count values in males and females undergoing a standardized 6-minute walk test. Methods: The study population was older adults (78.6 +/- 4.1 years) from the AGES-Reykjavik Study (N = 319). Participants performed a 6-minute walk test at a self-selected fast pace while wearing an ActiGraph GT3X at the hip. Vertical axis counts.s(-1) was the primary outcome. Covariates included walking speed, height, weight, BMI, waist circumference, femur length, and step length. Results: On average, males walked 7.2% faster than females (1.31 vs. 1.22 m.s(-1), P < .001) and had 32.3% greater vertical axis counts.s(-1) (54.6 vs. 39.4 counts.s(-1), P < .001). Accounting for walking speed reduced the sex difference to 19.2% and accounting for step length further reduced the difference to 13.4% (P < .001). Conclusion: Vertical axis counts.s(-1) were disproportionally greater in males even after adjustment for walking speed. This difference could confound free-living activity estimates.
C1 [Van Domelen, Dane R.] Emory Univ, Dept Biostat & Bioinformat, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.
[Caserotti, Paolo] Univ Southern Denmark, Inst Sports Sci & Clin Biomech, Odense, Denmark.
[Brychta, Robert J.; Chen, Kong Y.] Natl Inst Diabet Digest & Kidney Dis, Diabet Endocrinol & Obes Branch, Bethesda, MD USA.
[Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA.
[Patel, Kushang V.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA.
[Patel, Kushang V.] Univ Washington, Ctr Pain Res Impact Measurement & Effectiveness, Seattle, WA 98195 USA.
[Arnardottir, Nanna Yr; Eirikdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Arnardottir, Nanna Yr] Univ Iceland, Res Ctr Movement Sci, Reykjavik, Iceland.
[Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Johannsson, Erlingur] Univ Iceland, Res Ctr Sport & Hlth Sci, Sch Educ, Reykjavik, Iceland.
[Koster, Annemarie] NIA, Dept Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Koster, Annemarie] Maastricht Univ, Sch Publ Hlth & Primary Care, Dept Social Med, Med Ctr, Maastricht, Netherlands.
RP Van Domelen, DR (reprint author), Emory Univ, Dept Biostat & Bioinformat, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.
RI Sveinsson, Thorarinn/F-7554-2010; Koster, Annemarie/E-7438-2010;
Gudnason, Vilmundur/K-6885-2015;
OI Sveinsson, Thorarinn/0000-0001-8989-5514; Gudnason,
Vilmundur/0000-0001-5696-0084; Van Domelen, Dane/0000-0003-0051-7790;
Chen, Kong/0000-0002-0306-1904
FU Intramural NIH HHS; NIA NIH HHS [N01AG12100, N01-AG12100]
NR 37
TC 4
Z9 4
U1 1
U2 10
PU HUMAN KINETICS PUBL INC
PI CHAMPAIGN
PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA
SN 1543-3080
EI 1543-5474
J9 J PHYS ACT HEALTH
JI J. Phys. Act. Health
PD MAR
PY 2014
VL 11
IS 3
BP 626
EP 637
DI 10.1123/jpah.2012-0050
PG 12
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AF8RQ
UT WOS:000334983700022
PM 23417023
ER
PT J
AU Xing, J
Petranka, JG
Davis, FM
Desai, PN
Putney, JW
Bird, GS
AF Xing, Juan
Petranka, John G.
Davis, Felicity M.
Desai, Pooja N.
Putney, James W.
Bird, Gary S.
TI Role of Orai1 and store-operated calcium entry in mouse lacrimal gland
signalling and function
SO JOURNAL OF PHYSIOLOGY-LONDON
LA English
DT Article
ID ACINAR-CELLS; MOLECULAR-BASIS; T-LYMPHOCYTES; MICE LACKING; MAST-CELLS;
CHANNELS; POTENTIATION; SECRETION; DEPLETION; MODEL
AB Key points Lacrimal acinar cells from mice whose gene for Orai1 has been deleted have no detectable store-operated Ca2+ entry, whether assessed by measurement of cytoplasmic Ca2+ changes or as a store-operated current. Mice lacking Orai1 have diminished lacrimal fluid secretion in response to muscarinic-cholinergic stimulation. Mice lacking Orai1 also show diminished exocytosis, both in vivo and in vitro. The development and morphology of lacrimal glands, as well as responses not dependent on Ca2+ entry were unchanged in the knockout mice. The results demonstrate the central importance of store-operated Ca2+ entry in lacrimal exocrine function, and suggest possible strategies for combating diseases associated with diminished lacrimal secretion.
AbstractLacrimal glands function to produce an aqueous layer, or tear film, that helps to nourish and protect the ocular surface. Lacrimal glands secrete proteins, electrolytes and water, and loss of gland function can result in tear film disorders such as dry eye syndrome, a widely encountered and debilitating disease in ageing populations. To combat these disorders, understanding the underlying molecular signalling processes that control lacrimal gland function will give insight into corrective therapeutic approaches. Previously, in single lacrimal cells isolated from lacrimal glands, we demonstrated that muscarinic receptor activation stimulates a phospholipase C-coupled signalling cascade involving the inositol trisphosphate-dependent mobilization of intracellular calcium and the subsequent activation of store-operated calcium entry (SOCE). Since intracellular calcium stores are finite and readily exhausted, the SOCE pathway is a critical process for sustaining and maintaining receptor-activated signalling. Recent studies have identified the Orai family proteins as critical components of the SOCE channel activity in a wide variety of cell types. In this study we characterize the role of Orai1 in the function of lacrimal glands using a mouse model in which the gene for the calcium entry channel protein, Orai1, has been deleted. Our data demonstrate that lacrimal acinar cells lacking Orai1 do not exhibit SOCE following activation of the muscarinic receptor. In comparison with wild-type and heterozygous littermates, Orai1 knockout mice showed a significant reduction in the stimulated tear production following injection of pilocarpine, a muscarinic receptor agonist. In addition, calcium-dependent, but not calcium-independent exocytotic secretion of peroxidase was eliminated in glands from knockout mice. These studies indicate a critical role for Orai1-mediated SOCE in lacrimal gland signalling and function.
C1 [Xing, Juan; Petranka, John G.; Davis, Felicity M.; Desai, Pooja N.; Putney, James W.; Bird, Gary S.] NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Putney, JW (reprint author), NIEHS, NIH Chief Calcium Regulat Sect, POB 12233,111 Alexander Dr F255, Res Triangle Pk, NC 27709 USA.
EM putney@niehs.nih.gov
RI Davis, Felicity/P-1387-2016
OI Davis, Felicity/0000-0001-9112-118X
FU NIH, National Institute of Environmental Health Sciences
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Environmental Health Sciences.
NR 30
TC 4
Z9 5
U1 2
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3751
EI 1469-7793
J9 J PHYSIOL-LONDON
JI J. Physiol.-London
PD MAR 1
PY 2014
VL 592
IS 5
BP 927
EP 939
DI 10.1113/jphysiol.2013.267740
PG 13
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA AB8DU
UT WOS:000332021100013
PM 24297846
ER
PT J
AU Wouldes, TA
LaGasse, LL
Huestis, MA
DellaGrotta, S
Dansereau, LM
Lester, BM
AF Wouldes, Trecia A.
LaGasse, Linda L.
Huestis, Marilyn A.
DellaGrotta, Sheri
Dansereau, Lynne M.
Lester, Barry M.
TI Prenatal methamphetamine exposure and neurodevelopmental outcomes in
children from 1 to 3 years
SO NEUROTOXICOLOGY AND TERATOLOGY
LA English
DT Article
DE Prenatal exposure; Methamphetamine; Neurodevelopment; Longitudinal
ID INFANT DEVELOPMENT; MOTOR DEVELOPMENT; AMPHETAMINE ADDICTION; 8-YEAR-OLD
CHILDREN; RECREATIONAL DRUGS; SUBSTANCE USE; LIFE-STYLE; PREGNANCY;
MOTHERS; DEFICITS
AB Background: Despite the evidence that women world-wide are using methamphetamine (MA) during pregnancy little is known about the neurodevelopment of their children.
Design: The controlled, prospective longitudinal New Zealand (NZ) Infant Development, Environment and Lifestyle (IDEAL) study was carried out in Auckland, NZ. Participants were 103 children exposed to MA prenatally and 107 who were not exposed. The Mental Developmental Index (MDI) and the Psychomotor Developmental Index (PDI) of the Bayley Scales of Infant Development, Second Edition (BSID-II) measured cognitive and motor performances at ages 1, 2 and 3, and the Peabody Developmental Motor Scale, Second Edition (PDMSII) measured gross and fine motor performances at I and 3. Measures of the child's environment included the Home Observation of Measurement of the Environment and the Maternal Lifestyle Interview. The Substance Use Inventory measured maternal drug use.
Results: After controlling for other drug use and contextual factors, prenatal MA exposure was associated with poorer motor performance at 1 and 2 years on the BSID-II. No differences were observed for cognitive development (MDI). Relative to non-MA exposed children, longitudinal scores on the PDI and the gross motor scale of the PDMS-2 were 43 and 3.2 points lower, respectively. Being male and of Maori descent predicted lower cognitive scores (MDI) and being male predicted lower fine motor scores (PDMS-2).
Conclusions: Prenatal exposure to MA was associated with delayed gross motor development over the first 3 years, but not with cognitive development. However, being male and of Maori descent were both associated with poorer cognitive outcomes. Males in general did more poorly on tasks related to fine motor development. (C) 2014 Elsevier Inc All rights reserved.
C1 [Wouldes, Trecia A.] Univ Auckland, Fac Med & Hlth Sci, Dept Psychol Med, Auckland 1142, New Zealand.
[LaGasse, Linda L.; DellaGrotta, Sheri; Dansereau, Lynne M.; Lester, Barry M.] Brown Univ, Warren Alpert Med Sch, Brown Ctr Study Children Risk, Providence, RI 02905 USA.
[Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Wouldes, TA (reprint author), Univ Auckland, Fac Med & Hlth Sci, Dept Psychol Med, Private Bag 92019, Auckland 1142, New Zealand.
EM twouldes@auckland.ac.nz; Linda_LaGasse@brown.edu;
SDellaGrotta@Wihri.org; LDansereau@Wihri.org; Bany_Lester@brown.edu
OI Wouldes, Trecia/0000-0002-6609-8464
FU NIH [2R01DA014948]; National Institutes on Drug Abuse [RO1DA021757];
Auckland Medical Research Foundation
FX Funding and support: this work is part of the US and NZ Infant
Development Environment and Lifestyle Study funded by NIH grants:
National Institutes on Drug Abuse, 2R01DA014948 and RO1DA021757. The NZ
IDEAL study had additional support from the Auckland Medical Research
Foundation. None of the funders were involved in the design, collection,
analysis or interpretation of the data, the writing of the report or the
decision to submit this report.; NZ IDEAL study team: Jenny Rogers, BSc
(Nursing), PGCert Child & Adolescent Mental Health, Josephine Cliffe,
MPH, Suzanne Cumming, BSW, Heather Stewart, RN.
NR 63
TC 5
Z9 5
U1 3
U2 11
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0892-0362
EI 1872-9738
J9 NEUROTOXICOL TERATOL
JI Neurotoxicol. Teratol.
PD MAR-APR
PY 2014
VL 42
BP 77
EP 84
DI 10.1016/j.ntt.2014.02.004
PG 8
WC Neurosciences; Toxicology
SC Neurosciences & Neurology; Toxicology
GA AG0HH
UT WOS:000335096000010
PM 24566524
ER
PT J
AU Turkbey, B
Mena, E
Shih, J
Pinto, PA
Merino, MJ
Lindenberg, ML
Bernardo, M
McKinney, YL
Adler, S
Owenius, R
Choyke, PL
Kurdziel, KA
AF Turkbey, Baris
Mena, Esther
Shih, Joanna
Pinto, Peter A.
Merino, Maria J.
Lindenberg, Maria L.
Bernardo, Marcelino
McKinney, Yolanda L.
Adler, Stephen
Owenius, Rikard
Choyke, Peter L.
Kurdziel, Karen A.
TI Localized Prostate Cancer Detection with F-18 FACBC PET/CT: Comparison
with MR Imaging and Histopathologic Analysis
SO RADIOLOGY
LA English
DT Article
ID POSITRON-EMISSION-TOMOGRAPHY;
ANTI-1-AMINO-3-F-18-FLUOROCYCLOBUTANE-1-CARBOXYLIC ACID; C-11-ACETATE
PET/CT; INITIAL-EXPERIENCE; CARCINOMA; DIAGNOSIS
AB Purpose: To characterize uptake of 1-amino-3-fluorine 18-fluorocyclobutane-1-carboxylic acid (F-18 FACBC) in patients with localized prostate cancer, benign prostatic hyperplasia (BPH), and normal prostate tissue and to evaluate its potential utility in delineation of intraprostatic cancers in histopathologically confirmed localized prostate cancer in comparison with magnetic resonance (MR) imaging.
Materials and Methods: Institutional review board approval and written informed consent were obtained for this HIPAA-compliant prospective study. Twenty-one men underwent dynamic and static abdominopelvic F-18 FACBC combined positron emission tomography (PET) and computed tomography (CT) and multiparametric (MP) 3-T endorectal MR imaging before robotic-assisted prostatectomy. PET/CT and MR images were coregistered by using pelvic bones as fiducial markers; this was followed by manual adjustments. Whole-mount histopathologic specimens were sliced with an MR-based patient-specific mold. F-18 FACBC PET standardized uptake values (SUVs) were compared with those at MR imaging and histopathologic analysis for lesion- and sector-based (20 sectors per patient) analysis. Positive and negative predictive values for each modality were estimated by using generalized estimating equations with logit link function and working independence correlation structure.
Results: F-18 FACBC tumor uptake was rapid but reversible. It peaked 3.6 minutes after injection and reached a relative plateau at 15-20 minutes (SUVmax[15-20min]). Mean prostate tumor SUVmax(15-20min) was significantly higher than that of the normal prostate (4.5 +/- 0.5 vs 2.7 +/- 0.5) (P <.001); however, it was not significantly different from that of BPH (4.3 +/- 0.6) (P=.27). Sector-based comparison with histopathologic analysis, including all tumors, revealed sensitivity and specificity of 67% and 66%, respectively, for F-18 FACBC PET/CT and 73% and 79%, respectively, for T2-weighted MR imaging. F-18 FACBC PET/CT and MP MR imaging were used to localize dominant tumors (sensitivity of 90% for both). Combined 18F FACBC and MR imaging yielded positive predictive value of 82% for tumor localization, which was higher than that with either modality alone(P <.001).
Conclusion: F-18 FACBC PET/CT shows higher uptake in intraprostatic tumor foci than in normal prostate tissue; however, F-18 FACBC uptake in tumors is similar to that in BPH nodules. Thus, it is not specific for prostate cancer. Nevertheless, combined F-18 FACBC PET/CT and T2-weighted MR imaging enable more accurate localization of prostate cancer lesions than either modality alone. (C) RSNA, 2013
C1 [Turkbey, Baris; Mena, Esther; Lindenberg, Maria L.; Bernardo, Marcelino; McKinney, Yolanda L.; Adler, Stephen; Choyke, Peter L.; Kurdziel, Karen A.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
[Shih, Joanna] NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
[Pinto, Peter A.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Merino, Maria J.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
RP Turkbey, B (reprint author), NCI, Mol Imaging Program, NIH, 10 Ctr Dr,MSC 1182 Bldg 10,Room B3B85, Bethesda, MD 20892 USA.
EM turkbeyi@mail.nih.gov
FU National Institutes of Health [Z1A-BC-010655]
FX This research was supported by the National Institutes of Health (grant
no. Z1A-BC-010655).
NR 25
TC 33
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PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
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PD MAR
PY 2014
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BP 849
EP 856
DI 10.1148/radiol.13130240
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PM 24475804
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PT J
AU Catherino, WH
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Levy, G
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Levy, Gary
Malik, Minnie
Patel, Amrita
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SO REPRODUCTIVE SCIENCES
LA English
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C1 [Catherino, William H.; Britten, Joy; Levy, Gary; Malik, Minnie; Patel, Amrita] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
[Catherino, William H.; Levy, Gary] NICHHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
NR 0
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PI THOUSAND OAKS
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PY 2014
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[Diamond, Michael P.] Georgia Regents Univ, Dept Obstet & Gynecol, Augusta, GA USA.
[Armant, D. Randall] NICHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
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PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
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AU Zarek, SM
Nelson, LM
Segars, JH
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Yunce, M
Dumitriu, B
Wolff, EF
AF Zarek, Shvetha M.
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LA English
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C1 [Zarek, Shvetha M.; Nelson, Lawrence M.; Segars, James H.; DeCherney, Alan H.; Wolff, Erin F.] NICHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
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Libfraind, LL
Weitzel, RP
Woods, D
Feng, YL
Tilly, J
DeCherney, AH
Tisdale, JF
AF Wolff, Erin F.
Libfraind, Lauren L.
Weitzel, R. Patrick
Woods, Dori
Feng, Yanling
Tilly, Jonathan
DeCherney, Alan H.
Tisdale, John F.
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C1 [Wolff, Erin F.; Libfraind, Lauren L.; Feng, Yanling; DeCherney, Alan H.] NICHD, PRAE, NIH, Bethesda, MD USA.
[Wolff, Erin F.; Weitzel, R. Patrick; Tisdale, John F.] NHLBI, MCHB, NIH, Bethesda, MD 20892 USA.
[Woods, Dori; Tilly, Jonathan] Northeastern Univ, Boston, MA 02115 USA.
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AU Furcron, AE
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Hassan, Sonia
Gomez-Lopez, Nardhy
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C1 [Furcron, Amy-Eunice; StLouis, Derek; Hassan, Sonia; Gomez-Lopez, Nardhy] Wayne State Univ, Detroit, MI USA.
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StLouis, Derek
Romero, Roberto
Hassan, Sonia
Gomez-Lopez, Nardhy
TI Endotoxin Expands the Pool of Regulatory T Cells in Pregnancy but Not in
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C1 [Arenas-Hernandez, Marcia; StLouis, Derek; Hassan, Sonia; Gomez-Lopez, Nardhy] Wayne State Univ, Detroit, MI 48202 USA.
[Arenas-Hernandez, Marcia; StLouis, Derek; Romero, Roberto; Hassan, Sonia; Gomez-Lopez, Nardhy] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD 20892 USA.
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AF Clifton, Rebecca G.
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C1 [Clifton, Rebecca G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA.
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Fritz, Rani
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TI A Protein Panel for Early Gestation Detection of Adverse Pregnancy
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in the Endocervical Canal
SO REPRODUCTIVE SCIENCES
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C1 [Bolnick, Jay M.; Kilburn, Brian A.; Bolnick, Alan D.; Fritz, Rani; Armant, D. Randall] Wayne State Univ, Detroit, MI USA.
[Diamond, Michael P.] Georgia Regents Univ, Augusta, GA USA.
[Armant, D. Randall] NICHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
NR 0
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PU SAGE PUBLICATIONS INC
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PT J
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Dey, SK
Armant, DR
AF Bolnick, Alan D.
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Armant, D. Randall
CA NICHD Natl Cooperative Reprod
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[Diamond, Michael P.] Georgia Regents Univ, Augusta, GA USA.
[Dey, Sudhansu K.] Cincinnati Childrens Hosp, Div Reprod Sci, Cincinnati, OH USA.
[NICHD Natl Cooperative Reprod] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
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NR 0
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Sangi-Haghpeykar, H
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Sangi-Haghpeykar, Haley
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Lee, Wesley
Romero, Roberto
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[Romero, Roberto] NICHD, Perinatal Res Branch, NIH, DHHS, Detroit, MI USA.
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AU Jeyabalan, A
AF Jeyabalan, Arun
TI Do Differences in Arginase, Asymmetric Dimethylarginine and Nitric Oxide
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AF Myatt, Leslie
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PT J
AU Langenheim, JF
Fru, KN
Hestermann, EV
Yoo, JY
Jeong, JW
Yuan, LW
Young, SL
Lessey, BA
AF Langenheim, John F.
Fru, Karenne N.
Hestermann, Eli V.
Yoo, Jung Yoon
Jeong, Jae Wook
Yuan, Lingwen
Young, Steven L.
Lessey, Bruce A.
TI AhR and ARNT Are Overexpressed in the Endometrium of Women with
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C1 [Langenheim, John F.; Lessey, Bruce A.] Greenville Hlth Syst, Dept Obstet & Gynecol, Greenville, SC USA.
[Fru, Karenne N.] NICHD, PRAE SIOP, Bethesda, MD USA.
[Hestermann, Eli V.] Furman Univ, Dept Biol, Greenville, SC USA.
[Yoo, Jung Yoon; Jeong, Jae Wook] Michigan State Univ, Coll Human Med, Dept Obstet Gynecol & Reprod Biol, E Lansing, MI 48824 USA.
[Yuan, Lingwen; Young, Steven L.] Univ N Carolina, Sch Med, Dept Obstet & Gynecol, Chapel Hill, NC 27515 USA.
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PU SAGE PUBLICATIONS INC
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PD MAR
PY 2014
VL 21
IS 3
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ER
PT J
AU Royster, GD
Bochner, RZ
AF Royster, G. Donald
Bochner, Ronnie Z.
TI Greene Stirrups: A Novel Solution to a Global Problem
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C1 [Royster, G. Donald] NIH, Bethesda, MD 20892 USA.
[Bochner, Ronnie Z.] Robert Wood Johnson OB GYN Associates PA, Dept Obstet & Gynecol, Kendall Pk, NJ USA.
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PY 2014
VL 21
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BP 310A
EP 310A
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GA AE2OO
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ER
PT J
AU Muneyyirci-Delale, O
Charles, C
Nacharaju, V
Dalloul, M
Stratton, P
AF Muneyyirci-Delale, Ozgul
Charles, Cassandra
Nacharaju, Vijaya
Dalloul, Mudar
Stratton, Pamela
TI Changes in Urinary N-Telopeptide Levels in Women with Endometriosis on
Leuprolide vs Norethindrone Treatment
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LA English
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C1 [Muneyyirci-Delale, Ozgul; Charles, Cassandra; Nacharaju, Vijaya; Dalloul, Mudar] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA.
[Muneyyirci-Delale, Ozgul] Kings Cty Hosp Ctr, Brooklyn, NY USA.
[Stratton, Pamela] NICHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
NR 0
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PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
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PY 2014
VL 21
IS 3
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BP 312A
EP 312A
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WC Obstetrics & Gynecology; Reproductive Biology
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GA AE2OO
UT WOS:000333813003047
ER
PT J
AU Heitmann, RJ
Weitzel, RP
Feng, YL
Segars, JH
Tisdale, JF
Wolff, EF
AF Heitmann, Ryan J.
Weitzel, R. Pat
Feng, Yanling
Segars, James H.
Tisdale, John F.
Wolff, Erin F.
TI Uterine T-Regulatory Cell Depletion Decreases Implantation and Litter
Sizes in a Murine Model
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C1 [Heitmann, Ryan J.; Feng, Yanling; Segars, James H.; Wolff, Erin F.] NICHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Weitzel, R. Pat; Tisdale, John F.] NHLBI, NIH, Bethesda, MD 20892 USA.
NR 0
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PY 2014
VL 21
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BP 324A
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WC Obstetrics & Gynecology; Reproductive Biology
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GA AE2OO
UT WOS:000333813003082
ER
PT J
AU Naik, A
Rutledge, N
Romero, R
Hassan, S
Gomez-Lopez, N
AF Naik, Akshata
Rutledge, Nakisha
Romero, Roberto
Hassan, Sonia
Gomez-Lopez, Nardhy
TI Vaginal Progesterone, but Not 17OHP-C, Induces Changes in Decidual
Macrophages and Regulatory T Cells
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C1 [Naik, Akshata; Rutledge, Nakisha; Hassan, Sonia; Gomez-Lopez, Nardhy] Wayne State Univ, Detroit, MI USA.
[Naik, Akshata; Romero, Roberto; Hassan, Sonia; Gomez-Lopez, Nardhy] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.
NR 0
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SN 1933-7191
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PD MAR
PY 2014
VL 21
IS 3
SU S
BP 332A
EP 332A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AE2OO
UT WOS:000333813003107
ER
PT J
AU Platt, KM
Jarrell, AL
de Cabo, R
Pearson, KJ
AF Platt, Kristen M.
Jarrell, Alyssa L.
de Cabo, Rafael
Pearson, Kevin J.
TI Maternal Exercise Decreases Tumor Incidence in Mouse Offspring
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C1 [Platt, Kristen M.; Jarrell, Alyssa L.; Pearson, Kevin J.] Univ Kentucky, Grad Ctr Nutr Sci, Lexington, KY USA.
[de Cabo, Rafael] NIA, Translat Gerontol Branch, Intramural Res Program, Baltimore, MD 21224 USA.
RI de Cabo, Rafael/J-5230-2016
OI de Cabo, Rafael/0000-0002-3354-2442
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2014
VL 21
IS 3
SU S
BP 364A
EP 364A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AE2OO
UT WOS:000333813003200
ER
PT J
AU Zarek, SM
Dumitriu, B
Townsley, DM
DeCherney, AH
Young, NS
Wolff, EF
AF Zarek, Shvetha M.
Dumitriu, Bogdan
Townsley, Danielle M.
DeCherney, Alan H.
Young, Neal S.
Wolff, Erin F.
TI Telomere Lengths Are Not Reduced in Women with Infertility Compared to
Age Matched Controls
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Zarek, Shvetha M.; DeCherney, Alan H.; Wolff, Erin F.] NICHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Dumitriu, Bogdan; Townsley, Danielle M.; Young, Neal S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2014
VL 21
IS 3
SU S
BP 417A
EP 417A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AE2OO
UT WOS:000333813003355
ER
PT J
AU Petralia, RS
Mattson, MP
Yao, PJ
AF Petralia, Ronald S.
Mattson, Mark P.
Yao, Pamela J.
TI Communication breakdown: The impact of ageing on synapse structure
SO AGEING RESEARCH REVIEWS
LA English
DT Review
DE Synapse; Ageing; Postsynaptic density; Neurotransmitter vesicles;
Presynaptic bouton; Dendritic spine
ID LONG-TERM POTENTIATION; MONKEY PREFRONTAL-CORTEX; HIPPOCAMPAL AREA CA1;
RAT MEDIAL NUCLEUS; INNER HAIR-CELLS; AGE-RELATED LOSS; DENTATE GYRUS;
CALORIC RESTRICTION; NEUROMUSCULAR-JUNCTION; DENDRITIC SPINES
AB Impaired synaptic plasticity is implicated in the functional decline of the nervous system associated with ageing. Understanding the structure of ageing synapses is essential to understanding the functions of these synapses and their role in the ageing nervous system. In this review, we summarize studies on ageing synapses in vertebrates and invertebrates, focusing on changes in morphology and ultrastructure. We cover different parts of the nervous system, including the brain, the retina, the cochlea, and the neuromuscular junction. The morphological characteristics of aged synapses could shed light on the underlying molecular changes and their functional consequences. Published by Elsevier B.V.
C1 [Petralia, Ronald S.] NIDCD, Adv Imaging Core, NIH, Bethesda, MD 20892 USA.
[Mattson, Mark P.; Yao, Pamela J.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
RP Yao, PJ (reprint author), NIA, Neurosci Lab, NIH, Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM petralia@nidcd.nih.gov; yaopa@grc.nia.nih.gov
FU NIA/NIH; NIDCD/NIH
FX This work was supported by the Intramural Research Programs of the
NIA/NIH and NIDCD/NIH.
NR 145
TC 13
Z9 13
U1 0
U2 17
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 1568-1637
EI 1872-9649
J9 AGEING RES REV
JI Ageing Res. Rev.
PD MAR
PY 2014
VL 14
BP 31
EP 42
DI 10.1016/j.arr.2014.01.003
PG 12
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA AG0LT
UT WOS:000335107700003
PM 24495392
ER
PT J
AU Archambeault, DR
Yao, HHC
AF Archambeault, Denise R.
Yao, Humphrey Hung-Chang
TI Loss of Smad4 in Sertoli and Leydig Cells Leads to Testicular Dysgenesis
and Hemorrhagic Tumor Formation in Mice
SO BIOLOGY OF REPRODUCTION
LA English
DT Article
DE azoospermia; hemorrhage; Leydig cell hyperplasia; mouse; Smad; teratoma;
testicular dysgenesis; testis
ID GONADAL DEVELOPMENT; SIGNALING PATHWAYS; SEXUAL DEVELOPMENT;
SOMATIC-CELLS; ACTIVIN-A; BETA-B; TESTIS; MOUSE; DIFFERENTIATION;
VASCULATURE
AB As the central component of canonical TGFbeta superfamily signaling, SMAD4 is a critical regulator of organ development, patterning, tumorigenesis, and many other biological processes. Because numerous TGFbeta superfamily ligands are expressed in developing testes, there may exist specific requirements for SMAD4 in individual testicular cell types. Previously, we reported that expansion of the fetal testis cords requires expression of SMAD4 by the Sertoli cell lineage. To further uncover the role of Smad4 in murine testes, we produced conditional knockout mice lacking Smad4 in either Leydig cells or in both Sertoli and Leydig cells simultaneously. Loss of Smad4 concomitantly in Sertoli and Leydig cells led to underdevelopment of the testis cords during fetal life and mild testicular dysgenesis in young adulthood (decreased testis size, partially dysgenic seminiferous tubules, and low sperm production). When the Sertoli/Leydig cell Smad4 conditional knockout mice aged (56-to 62-wk old), the testis phenotypes became exacerbated with the appearance of hemorrhagic tumors, Leydig cell adenomas, and a complete loss of spermatogenesis. In contrast, loss of Smad4 in Leydig cells alone did not appreciably alter fetal and adult testis development. Our findings support a cell type-specific requirement of Smad4 in testis development and suppression of testicular tumors.
C1 [Archambeault, Denise R.; Yao, Humphrey Hung-Chang] Univ Illinois, Dept Comparat Biosci, Urbana, IL 61801 USA.
[Yao, Humphrey Hung-Chang] NIEHS, Reprod Dev Biol Grp, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA.
RP Yao, HHC (reprint author), NIEHS, NIH, 111 TW Alexander Dr,C4-10, Res Triangle Pk, NC 27709 USA.
EM yaoh3@niehs.nih.gov
RI Yao, Humphrey Hung-Chang/B-4795-2010
OI Yao, Humphrey Hung-Chang/0000-0003-2944-8469
FU National Institute of Health [HD046861]; NIEHS Intramural Research Fund
[ES102965, T32 ES07326]
FX Supported by National Institute of Health Grants HD046861 and NIEHS
Intramural Research Fund ES102965 (to H.H.Y.) and T32 ES07326 (to
D.R.A.).
NR 44
TC 5
Z9 6
U1 0
U2 6
PU SOC STUDY REPRODUCTION
PI MADISON
PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA
SN 0006-3363
EI 1529-7268
J9 BIOL REPROD
JI Biol. Reprod.
PD MAR
PY 2014
VL 90
IS 3
AR 62
DI 10.1095/biolreprod.113.111393
PG 10
WC Reproductive Biology
SC Reproductive Biology
GA AE9SY
UT WOS:000334351500012
PM 24501173
ER
PT J
AU Duncan, FE
Padilla-Banks, E
Bernhardt, ML
Ord, TS
Jefferson, WN
Moss, SB
Williams, CJ
AF Duncan, Francesca E.
Padilla-Banks, Elizabeth
Bernhardt, Miranda L.
Ord, Teri S.
Jefferson, Wendy N.
Moss, Stuart B.
Williams, Carmen J.
TI Transducin-Like Enhancer of Split-6 (TLE6) Is a Substrate of Protein
Kinase A Activity During Mouse Oocyte Maturation
SO BIOLOGY OF REPRODUCTION
LA English
DT Article
DE AKAP; meiosis; oocyte maturation; phosphorylation; PKA; subcortical
maternal complex
ID DEVELOPMENT IN-VITRO; MEIOTIC ARREST; MAMMALIAN OOCYTES; CYCLIC-AMP;
CAMP; PHOSPHORYLATION; INHIBITORS; GENE; EMBRYO; CELLS
AB Fully grown oocytes in the ovary are arrested at prophase of meiosis I because of high levels of intraoocyte cAMP that maintain increased levels of cAMP-dependent protein kinase (PKA) activity. Following the luteinizing hormone surge at the time of ovulation, cAMP levels drop, resulting in a reduction in PKA activity that triggers meiotic resumption. Although much is known about the molecular mechanisms of how PKA activity fluctuations initiate the oocyte's reentry into meiosis, significantly less is known about the requirement for PKA activity in the oocyte after exit from the prophase I arrest. Here we show that although PKA activity decreases in the oocyte upon meiotic resumption, it increases throughout meiotic progression from the time of germinal vesicle breakdown (GVBD) until the metaphase II (MII) arrest. Blocking this meiotic maturation-associated increase in PKA activity using the pharmacological inhibitor H89 resulted in altered kinetics of GVBD, defects in chromatin and spindle dynamics, and decreased ability of oocytes to reach MII. These effects appear to be largely PKA specific because inhibitors targeting other kinases did not have the same outcomes. To determine potential proteins that may require PKA phosphorylation during meiosis, we separated oocyte protein extracts on an SDS-PAGE gel, extracted regions of the gel that had corresponding immune reactivity towards an anti-PKA substrate antibody, and performed mass spectrometry and microsequencing. Using this approach, we identified transducin-like enhancer of split-6 (TLE6)-a maternal effect gene that is part of the subcortical maternal complex-as a putative PKA substrate. TLE6 localized to the oocyte cortex throughout meiosis in a manner that is spatially and temporally consistent with the localization of critical PKA subunits. Moreover, we demonstrated that TLE6 becomes phosphorylated in a narrow window following meiotic resumption, and H89 treatment can completely block this phosphorylation when added prior to GVBD but not after. Taken together, these results highlight the importance of oocyte-intrinsic PKA in regulating meiotic progression after the prophase I arrest and offer new insights into downstream targets of its activity.
C1 [Duncan, Francesca E.] Northwestern Univ, Feinberg Sch Med, Dept Obstet & Gynecol, Chicago, IL 60611 USA.
[Duncan, Francesca E.; Ord, Teri S.; Moss, Stuart B.; Williams, Carmen J.] Univ Penn Hlth Syst, Ctr Res Reprod & Womens Hlth, Philadelphia, PA USA.
[Padilla-Banks, Elizabeth; Bernhardt, Miranda L.; Jefferson, Wendy N.; Williams, Carmen J.] NIEHS, Reprod Med Grp, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA.
RP Duncan, FE (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Obstet & Gynecol, 303 E Super St,Lurie 10-250, Chicago, IL 60611 USA.
EM f-duncan@northwestern.edu
OI Bernhardt, Miranda/0000-0001-5424-5685
FU Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences [Z01ES102985]; NIH, National Institute of
Child Health and Human Development [HD044740]
FX Supported by the Intramural Research Program of the NIH, National
Institute of Environmental Health Sciences, grant number Z01ES102985,
and NIH, National Institute of Child Health and Human Development, grant
number HD044740 to C.J.W. and S.B.M. The authors declare no competing
financial interests.
NR 48
TC 2
Z9 2
U1 5
U2 8
PU SOC STUDY REPRODUCTION
PI MADISON
PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA
SN 0006-3363
EI 1529-7268
J9 BIOL REPROD
JI Biol. Reprod.
PD MAR
PY 2014
VL 90
IS 3
AR 63
DI 10.1095/biolreprod.113.112565
PG 12
WC Reproductive Biology
SC Reproductive Biology
GA AE9SY
UT WOS:000334351500013
PM 24501176
ER
PT J
AU Nakajima, T
Sano, K
Sato, K
Watanabe, R
Harada, T
Hanaoka, H
Choyke, PL
Kobayashi, H
AF Nakajima, Takahito
Sano, Kohei
Sato, Kazuhide
Watanabe, Rira
Harada, Toshiko
Hanaoka, Hirofumi
Choyke, Peter L.
Kobayashi, Hisataka
TI Fluorescence-lifetime molecular imaging can detect invisible peritoneal
ovarian tumors in bloody ascites
SO CANCER SCIENCE
LA English
DT Article
DE Fluorescence lifetime; fluorescence-guided surgery; hemorrhagic ascites;
molecular imaging; ovarian cancer
ID IN-VIVO; INDOCYANINE-GREEN; SERUM-ALBUMIN; HUMAN CANCER; MICROSCOPY;
FLAP; SKIN; FLUOROPHORE; PROTEIN; GFP
AB Blood contamination, such as bloody ascites or hemorrhages during surgery, is a potential hazard for clinical application of fluorescence imaging. In order to overcome this problem, we investigate if fluorescence-lifetime imaging helps to overcome this problem. Samples were prepared at concentrations ranging 0.3-2.4m and mixed with 0-10% of blood. Fluorescence intensities and lifetimes of samples were measured using a time-domain fluorescence imager. Ovarian cancer SHIN3 cells overexpressing the D-galactose receptor were injected into the peritoneal cavity 2.5weeks before the experiments. Galactosyl serum albumin-rhodamine green (GSA-RhodG), which bound to the D-galactose receptor and was internalized thereafter, was administered intraperitoneally to peritoneal ovarian cancer-bearing mice with various degrees of bloody ascites. In vitro study showed a linear correlation between fluorescence intensity and probe concentration (r(2)>0.99), whereas the fluorescence lifetime was consistent (range, 3.33 +/- 0.15-3.75 +/- 0.04ns). By adding 10% of blood to samples, fluorescence intensities decreased to <1%, while fluorescence lifetimes were consistent. Invivo fluorescence lifetime of GSA-RhodG stained tumors was longer than the autofluorescence lifetime (threshold, 2.87ns). Tumor lesions under hemorrhagic peritonitis were not depicted using fluorescence intensity imaging; however, fluorescence-lifetime imaging clearly detected tumor lesions by prolonged lifetimes. In conclusion, fluorescence-lifetime imaging with GSA-RhodG depicted ovarian cancer lesions, which were invisible in intensity images, in hemorrhagic ascites.
C1 [Nakajima, Takahito; Sano, Kohei; Sato, Kazuhide; Watanabe, Rira; Harada, Toshiko; Hanaoka, Hirofumi; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, NIH, Bldg 10,Room B3B69,MSC 1088, Bethesda, MD 20892 USA.
EM kobayash@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research
FX Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research
NR 26
TC 3
Z9 3
U1 2
U2 20
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1347-9032
EI 1349-7006
J9 CANCER SCI
JI Cancer Sci.
PD MAR
PY 2014
VL 105
IS 3
BP 308
EP 314
DI 10.1111/cas.12343
PG 7
WC Oncology
SC Oncology
GA AE0QC
UT WOS:000333670000009
PM 24479901
ER
PT J
AU Hessler, D
Fisher, L
Glasgow, RE
Strycker, LA
Dickinson, LM
Arean, PA
Masharani, U
AF Hessler, Danielle
Fisher, Lawrence
Glasgow, Russell E.
Strycker, Lisa A.
Dickinson, L. Miriam
Arean, Patricia A.
Masharani, Umesh
TI Reductions in Regimen Distress Are Associated With Improved Management
and Glycemic Control Over Time
SO DIABETES CARE
LA English
DT Article
ID DIABETES DISTRESS; DEPRESSIVE SYMPTOMS; CLINICAL DEPRESSION; OLDER
ADULTS; OUTCOMES; METAANALYSIS; ADHERENCE; STRESS; THERAPY; HUMANS
AB OBJECTIVECross-sectional and longitudinal associations among regimen distress (RD), self-management, and glycemic control were undertaken to explore mechanisms of operation among these variables.RESEARCH DESIGN AND METHODSIn a behavioral randomized control trial (RCT) to reduce RD, 392 adults with type 2 diabetes were assessed for RD, diet, exercise, medication adherence, and HbA(1c) at baseline and at 4 and 12 months. Associations among RD, self-management, and HbA(1c) were examined in cross-sectional analyses at baseline, in prospective analyses using baseline values to predict change over time, and in time-varying analyses.RESULTSAt baseline, greater RD and poorer medication adherence were independently associated with higher HbA(1c) (P = 0.05 and P < 0.001, respectively), and greater RD was associated with poorer medication adherence (P = 0.03). No consistent pattern of significant prospective associations was found. Significant time-varying findings showed that decreases in RD were associated with improvements in medication adherence (P < 0.01), physical activity (P < 0.001), and HbA(1c) (P = 0.02) over time following intervention. Changes in self-management were not associated with changes in HbA(1c) over time.CONCLUSIONSIn the context of an RCT to reduce distress, RD, self-management, and HbA(1c) were interrelated in cross-sectional and time-varying analyses. Decreases in RD were associated with improvements in both self-management and HbA(1c) over 12 months. Findings point to the complex and likely multifaceted pathways of association among these key constructs, with results indicating significant linkages between RD and both self-management and glycemic control over time.
C1 [Hessler, Danielle; Fisher, Lawrence; Arean, Patricia A.; Masharani, Umesh] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Glasgow, Russell E.] NCI, Div Canc Control & Populat Sci, Rockville, MD USA.
[Strycker, Lisa A.] Oregon Res Inst, Eugene, OR 97403 USA.
[Dickinson, L. Miriam] Univ Colorado, Aurora, CO USA.
RP Hessler, D (reprint author), Univ Calif San Francisco, San Francisco, CA 94143 USA.
EM hesslerd@fcm.ucsf.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases
[DK-061937]
FX This research was funded by National Institute of Diabetes and Digestive
and Kidney Diseases grant DK-061937.
NR 38
TC 18
Z9 20
U1 1
U2 7
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD MAR
PY 2014
VL 37
IS 3
BP 617
EP 624
DI 10.2337/dc13-0762
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AB3RT
UT WOS:000331708600014
PM 24170750
ER
PT J
AU Sarkar, G
Alattar, M
Brown, RJ
Quon, MJ
Harlan, DM
Rother, KI
AF Sarkar, Gayatri
Alattar, May
Brown, Rebecca J.
Quon, Michael J.
Harlan, David M.
Rother, Kristina I.
TI Exenatide Treatment for 6 Months Improves Insulin Sensitivity in Adults
With Type 1 Diabetes
SO DIABETES CARE
LA English
DT Article
ID RESISTANCE; GLUCOSE; CELL
AB OBJECTIVEExenatide treatment improves glycemia in adults with type 2 diabetes and has been shown to reduce postprandial hyperglycemia in adolescents with type 1 diabetes. We studied the effects of exenatide on glucose homeostasis in adults with long-standing type 1 diabetes.RESEARCH DESIGN AND METHODSFourteen patients with type 1 diabetes participated in a crossover study of 6 months' duration on exenatide (10 g four times a day) and 6 months off exenatide. We assessed changes in fasting and postprandial blood glucose and changes in insulin sensitivity before and after each study period.RESULTSHigh-dose exenatide therapy reduced postprandial blood glucose but was associated with higher fasting glucose concentrations without net changes in hemoglobin A(1c). Exenatide increased insulin sensitivity beyond the effects expected as a result of weight reduction.CONCLUSIONSExenatide is a promising adjunctive agent to insulin therapy because of its beneficial effects on postprandial blood glucose and insulin sensitivity in patients with type 1 diabetes.
C1 [Sarkar, Gayatri; Alattar, May; Brown, Rebecca J.; Rother, Kristina I.] Natl Inst Diabet & Digest & Kidney Dis, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD USA.
[Quon, Michael J.] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.
[Harlan, David M.] Univ Massachusetts, Sch Med, Dept Internal Med, Diabet Div, Worcester, MA USA.
[Harlan, David M.] UMass Mem Hlth Care, Worcester, MA USA.
RP Rother, KI (reprint author), Natl Inst Diabet & Digest & Kidney Dis, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD USA.
EM kristina.rother@nih.gov
OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases; National Institutes of Health Clinical
Center
FX This research was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases and the
National Institutes of Health Clinical Center.
NR 14
TC 29
Z9 29
U1 0
U2 2
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD MAR
PY 2014
VL 37
IS 3
BP 666
EP 670
DI 10.2337/dc13-1473
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AB3RT
UT WOS:000331708600020
PM 24194508
ER
PT J
AU Kim, C
Cleary, PA
Cowie, CC
Braffett, BH
Dunn, RL
Larkin, ME
Gatcomb, PM
Wessells, HB
Nathan, DM
Sarma, AV
AF Kim, Catherine
Cleary, Patricia A.
Cowie, Catherine C.
Braffett, Barbara H.
Dunn, Rodney L.
Larkin, Mary E.
Gatcomb, Patricia M.
Wessells, Hunter B.
Nathan, David M.
Sarma, Aruna V.
CA DCCT EDIC Res Grp
TI Effect of Glycemic Treatment and Microvascular Complications on
Menopause in Women With Type 1 Diabetes in the Diabetes Control and
Complications Trial/Epidemiology of Diabetes Interventions and
Complications (DCCT/EDIC) Cohort
SO DIABETES CARE
LA English
DT Article
ID PREMATURE OVARIAN FAILURE; ANTI-MULLERIAN HORMONE; INHIBIN B LEVELS;
MELLITUS; TRIAL; EPIDEMIOLOGY; AUTOIMMUNITY; DYSFUNCTION; THERAPY;
HISTORY
AB OBJECTIVEWe examined the impact of intensive versus conventional diabetes treatment upon menopause among women with type 1 diabetes in the Diabetes Control and Complications Trial (DCCT), a randomized controlled trial of intensive diabetes treatment, and its observational follow-up, the Epidemiology of Diabetes Interventions and Complications (EDIC) study.RESEARCH DESIGN AND METHODSIn a secondary analysis of women in the DCCT/EDIC (n = 657), outcomes were the cumulative incidences of natural menopause and surgical menopause. Cox regression analyses were used to examine associations with treatment group, time-varying estimates of hemoglobin A(1c) (HbA(1c)), insulin dosage, BMI, and microvascular complications (retinopathy, nephropathy, and neuropathy).RESULTSBy EDIC year 18, after an average of 28 years of follow-up, 240 (38%) women had experienced natural menopause and 115 (18%) women had experienced surgical menopause. Age at natural menopause was similar in the intensive versus conventional groups (49.9 vs. 49.0 years; P = 0.28), and age at surgical menopause was similar in the intensive versus conventional groups (40.8 vs. 42.0 years; P = 0.31). In multivariable models, treatment group, HbA(1c), and microvascular complications were not associated with risk of natural or surgical menopause. Each 10 unit/day increase in insulin dosage decreased risk of natural menopause (hazard ratio [HR] 0.91, 95% CI 0.75-0.98) and each kg/m(2) increase in BMI increased risk of surgical menopause (HR 1.08, 95% CI 1.00-1.16).CONCLUSIONSIn the DCCT/EDIC, intensive versus conventional treatment group and HbA(1c) level were not associated with menopause risk. Greater insulin dose was associated with lower menopause risk.
C1 [Kim, Catherine] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA.
[Kim, Catherine] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA.
[Cleary, Patricia A.; Braffett, Barbara H.] George Washington Univ, Biostat Ctr, Rockville, MD USA.
[Cowie, Catherine C.] Natl Inst Diabet & Digest & Kidney Dis, Bethesda, MD USA.
[Dunn, Rodney L.; Sarma, Aruna V.] Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA.
[Larkin, Mary E.; Nathan, David M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Diabet, Boston, MA USA.
[Gatcomb, Patricia M.] Yale Univ, Dept Med, New Haven, CT 06520 USA.
[Wessells, Hunter B.] Univ Washington, Dept Urol, Seattle, WA 98195 USA.
RP Kim, C (reprint author), Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA.
EM cathkim@umich.edu
FU Division of Diabetes Endocrinology and Metabolic Diseases of the
National Institute of Diabetes and Digestive and Kidney Diseases
[U01-DK-094176, U01-DK-094157]; National Eye Institute; National
Institute of Neurological Disorders and Stroke; Genetic Clinical
Research Centers Program; Clinical and Translational Science Center
Program, Bethesda, MD; U01 Cooperative Agreement; [R01-DK-083297]
FX The DCCT/EDIC has been supported by U01 Cooperative Agreement grants
(1982-93, 2011-2016) and contracts (1982-2011) with the Division of
Diabetes Endocrinology and Metabolic Diseases of the National Institute
of Diabetes and Digestive and Kidney Diseases (current grant numbers
U01-DK-094176 and U01-DK-094157) and through support by the National Eye
Institute, the National Institute of Neurological Disorders and Stroke,
the Genetic Clinical Research Centers Program (1993-2007), and the
Clinical and Translational Science Center Program (2006-present),
Bethesda, MD. Additional support for C. K. was provided by
R01-DK-083297.
NR 20
TC 8
Z9 8
U1 0
U2 1
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD MAR
PY 2014
VL 37
IS 3
BP 701
EP 708
DI 10.2337/dc13-1746
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AB3RT
UT WOS:000331708600025
PM 24170751
ER
PT J
AU Kalyani, RR
Lazo, M
Ouyang, P
Turkbey, E
Chevalier, K
Brancati, F
Becker, D
Vaidya, D
AF Kalyani, Rita Rastogi
Lazo, Mariana
Ouyang, Pamela
Turkbey, Evrim
Chevalier, Karinne
Brancati, Frederick
Becker, Diane
Vaidya, Dhananjay
TI Sex Differences in Diabetes and Risk of Incident Coronary Artery Disease
in Healthy Young and Middle-Aged Adults
SO DIABETES CARE
LA English
DT Article
ID PRIOR MYOCARDIAL-INFARCTION; AMERICAN-HEART-ASSOCIATION;
CARDIOVASCULAR-DISEASE; GENDER DISPARITIES; PRIMARY PREVENTION;
FOLLOW-UP; WOMEN; MEN; MORTALITY; IMPACT
AB OBJECTIVEControversy exists about the coronary artery disease (CAD) risk conveyed by diabetes in young and middle-aged women. We investigated sex differences in CAD by diabetes status among healthy individuals with different underlying risks of heart disease.RESEARCH DESIGN AND METHODSWe examined subjects aged <60 years without CAD at enrollment in the high-risk GeneSTAR Study (n = 1,448; follow-up approximate to 12 years), Multi-Ethnic Study of Atherosclerosis (MESA; n = 3,072; follow-up approximate to 7 years), and National Health and Nutrition Examination Survey III (NHANES III) Mortality Follow-up Study (n = 6,997; follow-up approximate to 15 years). Diabetes was defined by report, hypoglycemic use, and/or fasting glucose 126 mg/dL. The outcome was any CAD event during follow-up (fatal CAD in NHANES).RESULTSIn the absence of diabetes, CAD rates were lower among women in GeneSTAR, MESA, and NHANES (4.27, 1.66, and 0.40/1,000 person-years, respectively) versus men (11.22, 5.64, and 0.88/1,000 person-years); log-rank P < 0.001 (GeneSTAR/MESA) and P = 0.07 (NHANES). In the presence of diabetes, CAD event rates were similar among women (17.65, 7.34, and 2.37/1,000 person-years) versus men (12.86, 9.71, and 1.83/1,000 person-years); all log-rank P values > 0.05. Adjusting for demographics, diabetes was associated with a significant four- to fivefold higher CAD rate among women in each cohort, without differences in men. In meta-analyses of three cohorts, additionally adjusted for BMI, smoking, hypertension, HDL, and non-HDL cholesterol, antihypertensive and cholesterol-lowering medication use, the hazard ratio of CAD in men versus women among nondiabetes was 2.43 (1.76-3.35) and diabetes was 0.89 (0.43-1.83); P = 0.013 interaction by diabetes status.CONCLUSIONSThough young and middle-aged women are less likely to develop CAD in the absence of diabetes, the presence of diabetes equalizes the risk by sex. Our findings support aggressive CAD prevention strategies in women with diabetes and at similar levels to those that exist in men.
C1 [Kalyani, Rita Rastogi] Johns Hopkins Univ, Div Endocrinol, Baltimore, MD 21218 USA.
[Lazo, Mariana; Chevalier, Karinne; Brancati, Frederick; Becker, Diane; Vaidya, Dhananjay] Johns Hopkins Univ, Div Gen Internal Med, Baltimore, MD USA.
[Ouyang, Pamela] Johns Hopkins Bayview Med Ctr, Div Cardiol, Baltimore, MD USA.
[Turkbey, Evrim] NIH, Ctr Clin, Bethesda, MD 20892 USA.
RP Kalyani, RR (reprint author), Johns Hopkins Univ, Div Endocrinol, Baltimore, MD 21218 USA.
EM rrastogi@jhmi.edu
OI Vaidya, Dhananjay/0000-0002-7164-1601
FU National Institute of Diabetes and Digestive and Kidney Diseases
[K23-DK-093583, K24-DK-062222, P60-DK-079637]; National Heart, Lung, and
Blood Institute [N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162,
N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167,
N01-HC-95168, N01-HC-95169]; National Center for Research Resources
[UL1-RR-024156, UL1-RR-025005]; [U01-HL-72518-05]; [R01-HL-071025];
[R18-HL-58625]; [R01-NR-08153]; [R01-HL-49762]; [R01-HL-59684];
[R01-NR-02241]; [M01-RR-00052]
FX This work was supported by the National Institute of Diabetes and
Digestive and Kidney Diseases (grants K23-DK-093583, K24-DK-062222, and
P60-DK-079637). The GeneSTAR study was supported through various grants
(U01-HL-72518-05, R01-HL-071025, R18-HL-58625, R01-NR-08153,
R01-HL-49762, R01-HL-59684, R01-NR-02241, and M01-RR-00052). The MESA
study was supported by contracts N01-HC-95159 through N01-HC-95169 from
the National Heart, Lung, and Blood Institute and grants UL1-RR-024156
and UL1-RR-025005 from the National Center for Research Resources.
NR 36
TC 33
Z9 33
U1 2
U2 9
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD MAR
PY 2014
VL 37
IS 3
BP 830
EP 838
DI 10.2337/dc13-1755
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AB3RT
UT WOS:000331708600041
PM 24178997
ER
PT J
AU Brinton, LA
Cook, MB
McCormack, V
Johnson, KC
Olsson, H
Casagrande, JT
Cooke, R
Falk, RT
Gapstur, SM
Gaudet, MM
Gaziano, JM
Gkiokas, G
Guenel, P
Henderson, BE
Hollenbeck, A
Hsing, AW
Kolonel, LN
Isaacs, C
Lubin, JH
Michels, KB
Negri, E
Parisi, D
Petridou, ET
Pike, MC
Riboli, E
Sesso, HD
Snyder, K
Swerdlow, AJ
Trichopoulos, D
Ursin, G
van den Brandt, PA
Van Den Eeden, SK
Weiderpass, E
Willett, WC
Ewertz, M
Thomas, DB
AF Brinton, Louise A.
Cook, Michael B.
McCormack, Valerie
Johnson, Kenneth C.
Olsson, Hakan
Casagrande, John T.
Cooke, Rosie
Falk, Roni T.
Gapstur, Susan M.
Gaudet, Mia M.
Gaziano, J. Michael
Gkiokas, Georgios
Guenel, Pascal
Henderson, Brian E.
Hollenbeck, Albert
Hsing, Ann W.
Kolonel, Laurence N.
Isaacs, Claudine
Lubin, Jay H.
Michels, Karin B.
Negri, Eva
Parisi, Dominick
Petridou, Eleni Th.
Pike, Malcolm C.
Riboli, Elio
Sesso, Howard D.
Snyder, Kirk
Swerdlow, Anthony J.
Trichopoulos, Dimitrios
Ursin, Giske
van den Brandt, Piet A.
Van Den Eeden, Stephen K.
Weiderpass, Elisabete
Willett, Walter C.
Ewertz, Marianne
Thomas, David B.
CA European Rare Canc Study Grp
TI Anthropometric and Hormonal Risk Factors for Male Breast Cancer: Male
Breast Cancer Pooling Project Results
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID BASE-LINE CHARACTERISTICS; KLINEFELTER-SYNDROME; PROSTATE-CANCER; MEN;
COHORT; EPIDEMIOLOGY; NUTRITION; HEALTH; TESTOSTERONE; MORTALITY
AB The etiology of male breast cancer is poorly understood, partly because of its relative rarity. Although genetic factors are involved, less is known regarding the role of anthropometric and hormonally related risk factors.
In the Male Breast Cancer Pooling Project, a consortium of 11 casecontrol and 10 cohort investigations involving 2405 case patients (n 1190 from casecontrol and n 1215 from cohort studies) and 52013 control subjects, individual participant data were harmonized and pooled. Unconditional logistic regression generated study designspecific (casecontrol/cohort) odds ratios (ORs) and 95% confidence intervals (CIs), with exposure estimates combined using fixed effects meta-analysis. All statistical tests were two-sided.
Risk was statistically significantly associated with weight (highest/lowest tertile: OR 1.36; 95% CI 1.18 to 1.57), height (OR 1.18; 95% CI 1.01 to 1.38), and body mass index (BMI; OR 1.30; 95% CI 1.12 to 1.51), with evidence that recent rather than distant BMI was the strongest predictor. Klinefelter syndrome (OR 24.7; 95% CI 8.94 to 68.4) and gynecomastia (OR 9.78; 95% CI 7.52 to 12.7) were also statistically significantly associated with risk, relations that were independent of BMI. Diabetes also emerged as an independent risk factor (OR 1.19; 95% CI 1.04 to 1.37). There were also suggestive relations with cryptorchidism (OR 2.18; 95% CI 0.96 to 4.94) and orchitis (OR 1.43; 95% CI 1.02 to 1.99). Although age at onset of puberty and histories of infertility were unrelated to risk, never having had children was statistically significantly related (OR 1.29; 95% CI 1.01 to 1.66). Among individuals diagnosed at older ages, a history of fractures was statistically significantly related (OR 1.41; 95% CI 1.07 to 1.86).
Consistent findings across casecontrol and cohort investigations, complemented by pooled analyses, indicated important roles for anthropometric and hormonal risk factors in the etiology of male breast cancer. Further investigation should focus on potential roles of endogenous hormones.
C1 [Brinton, Louise A.; Cook, Michael B.; Falk, Roni T.; Lubin, Jay H.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[McCormack, Valerie] Int Agcy Res Canc, Sect Environm & Radiat, F-69372 Lyon, France.
[Johnson, Kenneth C.] Univ Ottawa, Dept Epidemiol & Community Med, Ottawa, ON, Canada.
[Olsson, Hakan] Lund Univ, Dept Oncol, Lund, Sweden.
[Casagrande, John T.; Henderson, Brian E.; Pike, Malcolm C.; Ursin, Giske] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA.
[Cooke, Rosie; Swerdlow, Anthony J.] Inst Canc Res, Div Genet & Epidemiol, Sutton, Surrey, England.
[Gapstur, Susan M.; Gaudet, Mia M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Michels, Karin B.] Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA.
[Sesso, Howard D.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA.
[Sesso, Howard D.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA.
[Gaziano, J. Michael] VA Boston Healthcare Syst, MAVERIC, Boston, MA USA.
[Gkiokas, Georgios] Aretaie Univ Hosp, Dept Surg, Athens, Greece.
[Guenel, Pascal] Univ Paris Sud, INSERM, Ctr Res Epidemiol & Populat Hlth, U1018, Villejuif, France.
[Hollenbeck, Albert] AARP, AARP Res, Washington, DC USA.
[Hsing, Ann W.] Canc Prevent Inst Calif, Fremont, CA USA.
[Hsing, Ann W.] Stanford Univ, Div Epidemiol, Dept Hlth Res & Policy, Palo Alto, CA 94304 USA.
[Hsing, Ann W.] Stanford Univ, Stanford Canc Inst, Stanford Sch Med, Stanford, CA USA.
[Kolonel, Laurence N.] Univ Hawaii, Ctr Canc, Canc Epidemiol Program, Honolulu, HI 96822 USA.
[Isaacs, Claudine] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA.
[Michels, Karin B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Michels, Karin B.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Negri, Eva; Trichopoulos, Dimitrios] Ist Richerche Farmacol, Milan, Italy.
[Parisi, Dominick; Snyder, Kirk] IMS Inc, Rockville, MD USA.
[Petridou, Eleni Th.] Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, GR-11527 Athens, Greece.
[Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, London, England.
[Sesso, Howard D.] Inst Canc Res, Div Prevent Med, London SW3 6JB, England.
[Sesso, Howard D.] Inst Canc Res, Div Aging, London SW3 6JB, England.
[Swerdlow, Anthony J.] Inst Canc Res, Div Breast Canc Res, London SW3 6JB, England.
[Ursin, Giske; Weiderpass, Elisabete] Canc Registry Norway, Oslo, Norway.
[Ursin, Giske] Univ Oslo, Inst Basic Med Sci, Dept Nutr, Oslo, Norway.
[van den Brandt, Piet A.] Maastricht Univ, Dept Epidemiol, Maastricht, Netherlands.
[Van Den Eeden, Stephen K.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA.
[Weiderpass, Elisabete] Arct Univ Norway, Univ Tromso, Fac Hlth Sci, Dept Community Med, Tromso, Norway.
[Weiderpass, Elisabete] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Weiderpass, Elisabete] Samfundet Folkhalsan, Helsinki, Finland.
[Ewertz, Marianne] Univ Southern Denmark, Inst Clin Res, Odense Univ Hosp, Dept Oncol, Odense, Denmark.
[Thomas, David B.] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA.
RP Brinton, LA (reprint author), NCI, NIH, Hormonal & Reprod Epidemiol Branch, 9609 Med Ctr Dr,Rm 7-E102,MSC 9774, Bethesda, MD 20892 USA.
EM brinton@nih.gov
RI Brinton, Louise/G-7486-2015; Cook, Michael/A-5641-2009; Weiderpass,
Elisabete/M-4029-2016
OI Brinton, Louise/0000-0003-3853-8562; Cook, Michael/0000-0002-0533-7302;
Weiderpass, Elisabete/0000-0003-2237-0128
FU European Research Council [ERC-2011-294576]; National Institutes of
Health, Bethesda, Maryland; Institute of Cancer Research acknowledges
National Health Service; Deutsche Krebshilfe; Deutsches
Krebsforschungszentrum; Federal Ministry of Education and Research
Germany; Swedish Cancer Society; Swedish Scientific Council; Regional
Government of Skane and Vasterbotten; Cancer Research UK; UK Medical
Research Council; Danish Cancer Society; Italian Association for
Research on Cancer; National Research Council Italy; HuGeF Foundation,
Torino, Italy; ISCIII RT ICC Red Tematica de Investigacion Cooperativa
en Cancer, Spain [R06/0020]; Hellenic Health Foundation; Stavros
Niarchos Foundation; Hellenic Ministry of Health and Social Solidarity
FX This research was funded in part by intramural funds from the National
Institutes of Health, Bethesda, Maryland. The Swedish Case-Control Study
acknowledges the support of the European Research Council Advanced Grant
ERC-2011-294576. The Institute of Cancer Research acknowledges National
Health Service funding to the National Institute for Health Research
Biomedical Research Centre. The principle investigators and funders
corresponding to each of the EPIC centers that contributed cases were
Heiner Boeing, Rudolph Kaaks (Germany); Goran Hallmans, Jonas Manjer
(Sweden); Timothy Key, Nick Wareham (UK); Kim Overvad, Anne Tjonneland
(Denmark); Domenico Palli, Paolo Vineis, Rosario Tumino (Italy); Maria
Jose Sanchez (Spain); Antonia Trichopoulou (Greece); from the Deutsche
Krebshilfe, Deutsches Krebsforschungszentrum and the Federal Ministry of
Education and Research Germany; the Swedish Cancer Society, Swedish
Scientific Council and the Regional Government of Skane and
Vasterbotten; Cancer Research UK and the UK Medical Research Council;
Danish Cancer Society; Italian Association for Research on Cancer,
National Research Council Italy, and HuGeF Foundation, Torino, Italy;
ISCIII RT ICC Red Tematica de Investigacion Cooperativa en Cancer
(R06/0020) Spain; Hellenic Health Foundation, the Stavros Niarchos
Foundation and the Hellenic Ministry of Health and Social Solidarity.
NR 53
TC 28
Z9 28
U1 1
U2 14
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
EI 1460-2105
J9 JNCI-J NATL CANCER I
JI JNCI-. Natl. Cancer Inst.
PD MAR
PY 2014
VL 106
IS 3
AR djt465
DI 10.1093/jnci/djt465
PG 11
WC Oncology
SC Oncology
GA AF4NY
UT WOS:000334691200012
PM 24552677
ER
PT J
AU Kristal, AR
Darke, AK
Morris, JS
Tangen, CM
Goodman, PJ
Thompson, IM
Meyskens, FL
Goodman, GE
Minasian, LM
Parnes, HL
Lippman, SM
Klein, EA
AF Kristal, Alan R.
Darke, Amy K.
Morris, J. Steven
Tangen, Catherine M.
Goodman, Phyllis J.
Thompson, Ian M.
Meyskens, Frank L., Jr.
Goodman, Gary E.
Minasian, Lori M.
Parnes, Howard L.
Lippman, Scott M.
Klein, Eric A.
TI Baseline Selenium Status and Effects of Selenium and Vitamin E
Supplementation on Prostate Cancer Risk
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID PREVENTION TRIAL SELECT; RANDOMIZED CONTROLLED-TRIAL; BETA-CAROTENE;
TOENAILS; MEN; CHEMOPREVENTION; CARCINOGENESIS; METAANALYSIS; HEALTH;
BLOOD
AB The Selenium and Vitamin E Cancer Prevention Trial found no effect of selenium supplementation on prostate cancer (PCa) risk but a 17% increased risk from vitamin E supplementation. This casecohort study investigates effects of selenium and vitamin E supplementation conditional upon baseline selenium status.
There were 1739 total and 489 high-grade (Gleason 710) PCa cases and 3117 men in the randomly selected cohort. Proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for effects of supplementation within quintiles of baseline toenail selenium. Cox proportional hazards models were used to estimate hazard ratios, and all statistical tests are two-sided.
Toenail selenium, in the absence of supplementation, was not associated with PCa risk. Selenium supplementation (combined selenium only and selenium vitamin E arms) had no effect among men with low selenium status (< 60th percentile of toenail selenium) but increased the risk of high-grade PCa among men with higher selenium status by 91% (P .007). Vitamin E supplementation (alone) had no effect among men with high selenium status (40th percentile of toenail selenium) but increased the risks of total, low-grade, and high-grade PCa among men with lower selenium status (63%, P .02; 46%, P .09; 111%, P .008, respectively).
Selenium supplementation did not benefit men with low selenium status but increased the risk of high-grade PCa among men with high selenium status. Vitamin E increased the risk of PCa among men with low selenium status. Men should avoid selenium or vitamin E supplementation at doses that exceed recommended dietary intakes.
C1 [Kristal, Alan R.] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98122 USA.
[Darke, Amy K.; Tangen, Catherine M.; Goodman, Phyllis J.] Fred Hutchinson Canc Res Ctr, SWOG Stat Ctr, Seattle, WA 98122 USA.
[Kristal, Alan R.; Goodman, Gary E.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Goodman, Gary E.] Univ Washington, Dept Environm Hlth, Seattle, WA 98195 USA.
[Morris, J. Steven] Univ Missouri, Res Reactor Ctr, Columbia, MO USA.
[Morris, J. Steven] Harry S Truman Mem Vet Hosp, Columbia, MO 65201 USA.
[Thompson, Ian M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA.
[Meyskens, Frank L., Jr.] Univ Calif Irvine, Chao Family Comprehens Canc Ctr, Irvine, CA USA.
[Minasian, Lori M.; Parnes, Howard L.] NCI, NIH, Canc Prevent Div, Bethesda, MD 20892 USA.
[Lippman, Scott M.] Univ Calif San Diego, Moores Canc Ctr, San Diego, CA 92103 USA.
[Klein, Eric A.] Cleveland Clin, Glickman Urol & Kidney Inst, Cleveland, OH 44106 USA.
RP Kristal, AR (reprint author), Fred Hutchinson Canc Res Ctr, Canc Prevent Program, 1100 Fairview Ave N,M4-B402, Seattle, WA 98122 USA.
EM akristal@fhcrc.org
OI Kristal, Alan/0000-0002-7329-1617
FU Public Health Service - National Cancer Institute, Division of Cancer
Prevention, National Institutes of Health, Department of Health and
Human Services [U10 CA037429]; National Center for Complementary and
Alternative Medicine (National Institutes of Health)
FX This work was supported in part by Public Health Service Cooperative
Agreement grant U10 CA037429 awarded by the National Cancer Institute,
Division of Cancer Prevention, National Institutes of Health, Department
of Health and Human Services, and by the National Center for
Complementary and Alternative Medicine (National Institutes of Health).
Study agents and packaging were provided by Sabinsa Corporation
(Piscataway, NJ), Tishcon Corporation (Westbury, NY), and DSM
Nutritional Products Inc (Parsipanny, NJ). Optional study multivitamins
were provided by Perrigo Company (Allegan, MI).
NR 32
TC 34
Z9 36
U1 2
U2 20
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
EI 1460-2105
J9 JNCI-J NATL CANCER I
JI JNCI-. Natl. Cancer Inst.
PD MAR
PY 2014
VL 106
IS 3
AR djt456
DI 10.1093/jnci/djt456
PG 8
WC Oncology
SC Oncology
GA AF4NY
UT WOS:000334691200003
PM 24563519
ER
PT J
AU Bechor, M
Pettit, JW
Silverman, WK
Bar-Haim, Y
Abend, R
Pine, DS
Vasey, MW
Jaccard, J
AF Bechor, Michele
Pettit, Jeremy W.
Silverman, Wendy K.
Bar-Haim, Yair
Abend, Rany
Pine, Daniel S.
Vasey, Michael W.
Jaccard, James
TI Attention Bias Modification Treatment for children with anxiety
disorders who do not respond to cognitive behavioral therapy: a case
series
SO JOURNAL OF ANXIETY DISORDERS
LA English
DT Article
DE Anxiety; Children; Attention; Treatment; Attention bias
ID RANDOMIZED CLINICAL-TRIAL; SELECTIVE ATTENTION; ANXIOUS CHILDREN; SOCIAL
PHOBIA; ANGRY FACES; ADOLESCENTS; DEPRESSION; INDIVIDUALS; RELIABILITY;
VALIDITY
AB Evidence is emerging to support the promise of Attention Bias Modification Treatment (ABMT), a computer-based attention training program, in reducing anxiety in children. ABMT has not been tested as an adjuvant for children with anxiety disorders who do not respond to Cognitive-Behavioral Therapy (CBT). This case series presents findings from an open trial of ABMT among six children (four girls; M age = 11.2 years) who completed a CBT protocol and continued to meet diagnostic criteria for an anxiety disorder. All children completed the ABMT protocol with no canceled or missed sessions. Child self-ratings on anxiety symptoms and depressive symptoms significantly decreased from pretreatment to posttreatment, as did parent ratings on child anxiety-related impairment. Parent ratings on child anxiety and internalizing symptoms displayed non-significant decreases from pretreatment to posttreatment. These findings support the potential promise of ABMT as a feasible adjuvant treatment that reduces anxiety and impairment among child anxiety CBT nonresponders. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Bechor, Michele; Pettit, Jeremy W.; Silverman, Wendy K.] Florida Int Univ, Dept Psychol, Miami, FL 33199 USA.
[Bar-Haim, Yair; Abend, Rany] Tel Aviv Univ, Dept Psychol, Adler Ctr Res Child Dev & Psychopathol, IL-69978 Tel Aviv, Israel.
[Pine, Daniel S.] NIMH, Intramural Res Program, Bethesda, MD 20892 USA.
[Vasey, Michael W.] Ohio State Univ, Dept Psychol, Columbus, OH 43210 USA.
[Jaccard, James] NYU, Silver Sch Social Work, New York, NY USA.
RP Pettit, JW (reprint author), Florida Int Univ, Dept Psychol, Miami, FL 33199 USA.
EM jpettit@fiu.edu
FU NIMH NIH HHS [MH079943, MH097931, R01 MH079943, R34 MH097931]
NR 43
TC 9
Z9 9
U1 7
U2 27
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0887-6185
EI 1873-7897
J9 J ANXIETY DISORD
JI J. Anxiety Disord.
PD MAR
PY 2014
VL 28
IS 2
BP 154
EP 159
DI 10.1016/j.janxdis.2013.09.001
PG 6
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA AF2RI
UT WOS:000334559300006
PM 24211147
ER
PT J
AU Borges, S
Chen, YF
Laughren, TP
Temple, R
Patel, HD
David, PA
Mathis, M
Unger, E
Yang, PL
Khin, NA
AF Borges, Silvana
Chen, Yeh-Fong
Laughren, Thomas P.
Temple, Robert
Patel, Hiren D.
David, Paul A.
Mathis, Mitchell
Unger, Ellis
Yang, Peiling
Khin, Ni A.
TI Review of Maintenance Trials for Major Depressive Disorder: A 25-Year
Perspective From the US Food and Drug Administration
SO JOURNAL OF CLINICAL PSYCHIATRY
LA English
DT Review
ID RELAPSE PREVENTION; RESIDUAL SYMPTOMS; METAANALYSIS; ANTIDEPRESSANTS;
RECURRENCE; REMISSION; RECOVERY
AB Objective: The maintenance efficacy of antidepressants is usually assessed in postmarketing studies with a randomized withdrawal design. This report explores differences in relapse rates, trial characteristics, and success rates in maintenance efficacy studies submitted to the US Food and Drug Administration (FDA) over a 25-year period.
Data Sources: Clinical data from all maintenance trials with antidepressants submitted to FDA between 1987 and 2012.
Study Selection: Efficacy data were compiled from 15 maintenance clinical trials in adults diagnosed with major depressive disorder according to DSM-III or DSM-IV criteria. Data Extraction: Trial characteristics, relapse rates, and time to relapse in each study were examined.
Results: Relapse rates were significantly lower (P <.05) in the drug arm than in the placebo arm in every study, with a mean relapse rate difference of 18% and an average percent reduction in relapse rate of 52% compared to placebo. Only 6% of the relapse events occurred in the first 2 weeks of the doubleblind phase. The separation between treatment arms continued to increase throughout the double-blind phase only in the trial with longest response stabilization period.
Conclusions: Antidepressant maintenance trials have a high rate of success, indicating a benefit of continuing drug treatment after initial response to an antidepressant. This benefit appears to result mainly from a decreased rate of recurrent depression rather than from an effect of drug withdrawal in the placebo groups.
C1 [Borges, Silvana; Patel, Hiren D.; David, Paul A.; Mathis, Mitchell] Food & Drug Adm 1, Div Psychiat Prod, Off New Drugs, Silver Spring, MD 20993 USA.
[Temple, Robert] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
[Laughren, Thomas P.] Massachusetts Gen Hosp, Clin Trials Network & Inst, Boston, MA USA.
[Laughren, Thomas P.] NIMH, Bethesda, MD 20892 USA.
RP Borges, S (reprint author), Food & Drug Adm, Div Psychiat Prod, 10903 New Hampshire Ave,Bldg 22,Rm 4159, Silver Spring, MD 20993 USA.
EM silvana.borges@fda.hhs.gov
NR 24
TC 17
Z9 17
U1 4
U2 11
PU PHYSICIANS POSTGRADUATE PRESS
PI MEMPHIS
PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA
SN 0160-6689
EI 1555-2101
J9 J CLIN PSYCHIAT
JI J. Clin. Psychiatry
PD MAR
PY 2014
VL 75
IS 3
BP 205
EP 214
DI 10.4088/JCP.13r08722
PG 10
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA AF0RP
UT WOS:000334422000005
PM 24717376
ER
PT J
AU Yang, Z
Wu, PL
Weng, XC
Bandettini, PA
AF Yang, Zhi
Wu, Paula
Weng, Xuchu
Bandettini, Peter A.
TI Cerebellum engages in automation of verb-generation skill
SO JOURNAL OF INTEGRATIVE NEUROSCIENCE
LA English
DT Article
DE Cerebellum; functional MRI; verb generation; skill learning
ID POSITRON-EMISSION-TOMOGRAPHY; COGNITIVE-AFFECTIVE SYNDROME;
WORKING-MEMORY; FUNCTIONAL TOPOGRAPHY; PREFRONTAL CORTEX; BASAL GANGLIA;
ACTIVATION; ANATOMY; MOTOR; INVOLVEMENT
AB Numerous studies have shown cerebellar involvement in item-specific association, a form of explicit learning. However, very few have demonstrated cerebellar participation in automation of non-motor cognitive tasks. Applying fMRI to a repeated verb-generation task, we sought to distinguish cerebellar involvement in learning of item-specific noun-verb association and automation of verb generation skill. The same set of nouns was repeated in six verb-generation blocks so that subjects practiced generating verbs for the nouns. The practice was followed by a novel block with a different set of nouns. The cerebellar vermis (IV/ V) and the right cerebellar lobule VI showed decreased activation following practice; activation in the right cerebellar Crus I was significantly lower in the novel challenge than in the initial verb-generation task. Furthermore, activation in this region during well-practiced blocks strongly correlated with improvement of behavioral performance in both the well-practiced and the novel blocks, suggesting its role in the learning of general mental skills not specific to the practiced noun-verb pairs. Therefore, the cerebellum processes both explicit verbal associative learning and automation of cognitive tasks. Different cerebellar regions predominate in this processing: lobule VI during the acquisition of item-specific association, and Crus I during automation of verb-generation skills through practice.
C1 [Yang, Zhi] Chinese Acad Sci, Inst Psychol, Key Lab Behav Sci, Beijing 100101, Peoples R China.
[Yang, Zhi; Wu, Paula; Bandettini, Peter A.] NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
[Weng, Xuchu] Hangzhou Normal Univ, Ctr Cognit & Brain Disorders, Hangzhou 310015, Zhejiang, Peoples R China.
RP Yang, Z (reprint author), Chinese Acad Sci, Inst Psychol, Key Lab Behav Sci, 16 Lincui Rd, Beijing 100101, Peoples R China.
EM yangz@psych.ac.cn
OI Yang, Zhi/0000-0002-2222-2312
FU National Key Technologies R&D Program of China [2012BAI36B01]; Natural
Science Foundation of China [81270023]; National Institute of Mental
Health; National Institutes of Health
FX This work was supported by National Key Technologies R&D Program of
China (No. 2012BAI36B01) and Natural Science Foundation of China
(81270023). ZY, PW and PAB are supported by the Intramural Research
Program of the National Institute of Mental Health, National Institutes
of Health.
NR 56
TC 0
Z9 1
U1 0
U2 8
PU IMPERIAL COLLEGE PRESS
PI LONDON
PA 57 SHELTON ST, COVENT GARDEN, LONDON WC2H 9HE, ENGLAND
SN 0219-6352
EI 1757-448X
J9 J INTEGR NEUROSCI
JI J. Integr. Neurosci.
PD MAR
PY 2014
VL 13
IS 1
BP 1
EP 17
DI 10.1142/S0219635214500010
PG 17
WC Neurosciences
SC Neurosciences & Neurology
GA AF4OE
UT WOS:000334692000001
PM 24738536
ER
PT J
AU Kathawala, RJ
Sodani, K
Chen, K
Patel, A
Abuznait, AH
Anreddy, N
Sun, YL
Kaddoumi, A
Ashby, CR
Chen, ZS
AF Kathawala, Rishil J.
Sodani, Kamlesh
Chen, Kang
Patel, Atish
Abuznait, Alaa H.
Anreddy, Nagaraju
Sun, Yue-Li
Kaddoumi, Amal
Ashby, Charles R., Jr.
Chen, Zhe-Sheng
TI Masitinib Antagonizes ATP-Binding Cassette Subfamily C Member
10-Mediated Paclitaxel Resistance: A Preclinical Study
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Article
ID GASTROINTESTINAL STROMAL TUMORS; REVERSES MULTIDRUG-RESISTANCE; TYROSINE
KINASE INHIBITOR; CANCER-CELLS; IN-VIVO; DRUG-RESISTANCE; EFFLUX
ACTIVITY; ABCC10 MRP7; B MEMBER-1; IMATINIB
AB Paclitaxel displays clinical activity against a wide variety of solid tumors. However, resistance to paclitaxel significantly attenuates the response to chemotherapy. The ABC transporter subfamily C member 10 (ABCC10), also known as multidrug resistance protein 7 (MRP7) efflux transporter, is a major mediator of paclitaxel resistance. In this study, we show that masitinib, a small molecule stem-cell growth factor receptor (cKit) tyrosine kinase inhibitor, at nontoxic concentrations, significantly attenuates paclitaxel resistance in HEK293 cells transfected with ABCC10. Our in vitro studies indicated that masitinib (2.5 mu mol/L) enhanced the intracellular accumulation and decreased the efflux of paclitaxel by inhibiting the ABCC10 transport activity without altering the expression level of ABCC10 protein. Furthermore, masitinib, in combination with paclitaxel, significantly inhibited the growth of ABCC10-expressing tumors in nude athymic mice in vivo. Masitinib administration also resulted in a significant increase in the levels of paclitaxel in the plasma, tumors, and lungs compared with paclitaxel alone. In conclusion, the combination of paclitaxel and masitinib could serve as a novel and useful therapeutic strategy to reverse paclitaxel resistance mediated by ABCC10. (C)2014 AACR.
C1 [Kathawala, Rishil J.; Sodani, Kamlesh; Patel, Atish; Anreddy, Nagaraju; Sun, Yue-Li; Ashby, Charles R., Jr.; Chen, Zhe-Sheng] St Johns Univ, Coll Pharm & Hlth Sci, Dept Pharmaceut Sci, Jamaica, NY 11439 USA.
[Chen, Kang] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Chen, Kang] Barbara Ann Karmanos Canc Inst, Tumor & Microenvironm Program, Detroit, MI USA.
[Chen, Kang] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Bethesda, MD USA.
[Chen, Kang] NIAID, Mucosal Immunol Studies Team, NIH, Bethesda, MD 20892 USA.
[Abuznait, Alaa H.; Kaddoumi, Amal] Univ Louisiana, Coll Pharm, Dept Basic Pharmaceut Sci, Monroe, LA USA.
RP Chen, ZS (reprint author), St Johns Univ, Dept Pharmaceut Sci, Queens, NY 11439 USA.
EM ashbyc@stjohns.edu; chenz@stjohns.edu
RI Patel, Atish/J-4699-2014
OI Anreddy, Nagaraju/0000-0001-8914-8404; Patel, Atish/0000-0002-5549-9166
FU NCI NIH HHS [1R15CA143701, R15 CA143701]
NR 37
TC 12
Z9 13
U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1535-7163
EI 1538-8514
J9 MOL CANCER THER
JI Mol. Cancer Ther.
PD MAR
PY 2014
VL 13
IS 3
BP 714
EP 723
DI 10.1158/1535-7163.MCT-13-0743
PG 10
WC Oncology
SC Oncology
GA AE9HU
UT WOS:000334318300015
PM 24431074
ER
PT J
AU Tuccillo, FM
Palmieri, C
Fiume, G
de Laurentiis, A
Schiavone, M
Falcone, C
Iaccino, E
Galandrini, R
Capuano, C
Santoni, A
D'Armiento, FP
Arra, C
Barbieri, A
Dal Piaz, F
Venzon, D
Bonelli, P
Buonaguro, FM
Scala, I
Mallardo, M
Quinto, I
Scala, G
AF Tuccillo, Franca Maria
Palmieri, Camillo
Fiume, Giuseppe
de Laurentiis, Annamaria
Schiavone, Marco
Falcone, Cristina
Iaccino, Enrico
Galandrini, Ricciarda
Capuano, Cristina
Santoni, Angela
D'Armiento, Francesco Paolo
Arra, Claudio
Barbieri, Antonio
Dal Piaz, Fabrizio
Venzon, David
Bonelli, Patrizia
Buonaguro, Franco Maria
Scala, Iris
Mallardo, Massimo
Quinto, Ileana
Scala, Giuseppe
TI Cancer-Associated CD43 Glycoforms as Target of Immunotherapy
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Article
ID KAPPA-B-ALPHA; MONOCLONAL-ANTIBODIES; FUNCTIONAL-CHARACTERIZATION;
THYMIC ANTIGEN; PEPTIDE; PHAGE; MIMOTOPES; CELLS; VACCINATION;
EXPRESSION
AB CD43 is a sialoglycosylated membrane protein that is involved in cell proliferation and differentiation. CD43 glycoforms that are recognized by the UN1 monoclonal antibody (mAb) were expressed in lymphoblastoid T-cell lines and solid tumors, such as breast, colon, gastric, and squamous cell lung carcinomas, while unexpressed in the normal counterparts. The cancer association of UN1/CD43 epitope suggested the possibility to use the UN1 mAb for tumor diagnosis and therapy. In this study, we show that the UN1 mAb was endowed with antitumor activity in vivo because its passive transfer inhibited the growth of UN1-positive HPB-ALL lymphoblastoid T cells in mice. Furthermore, we demonstrate that tumor inhibition was due to UN1 mAb-dependent natural killer-mediated cytotoxicity. By screening a phage-displayed random peptide library, we identified the phagotope 2/165 as a mimotope of the UN1 antigen, as it harbored a peptide sequence that was specifically recognized by the UN1mAb and inhibited the binding of the UN1mAb to UN1-positive tumor cells. On the basis of sequence homology with the extracellular region of CD43 (amino acids 64 to 83), the 2/165 peptide sequence was likely mimicking the protein core of the UN1/CD43 epitope. When used as vaccine in mice, the 2/165 phagotope raised antibodies against the UN1/CD43 antigen, indicating that the 2/165 phagotope mimicked the UN1 antigen structure, and could represent a novel immunogen for cancer immunotherapy. These findings support the feasibility of using monoclonal antibodies to identify cancer associated mimotopes for immunotherapy. (C)2013 AACR.
C1 [Tuccillo, Franca Maria; Bonelli, Patrizia; Buonaguro, Franco Maria] Fdn G Pascale IRCCS, Ist Nazl Studio & Cura Tumori, Lab Mol Biol & Viral Oncogenesis, Naples, Italy.
[Arra, Claudio; Barbieri, Antonio] Fdn G Pascale IRCCS, Ist Nazl Studio & Cura Tumori, Anim Facil, Naples, Italy.
[D'Armiento, Francesco Paolo] Univ Naples Federico II, Dept Adv Biomed Sci, Naples, Italy.
[Scala, Iris] Univ Naples Federico II, Dept Pediat, Naples, Italy.
[Mallardo, Massimo] Univ Naples Federico II, Dept Mol Med & Med Biotechnol, Naples, Italy.
[Palmieri, Camillo; Fiume, Giuseppe; de Laurentiis, Annamaria; Schiavone, Marco; Falcone, Cristina; Iaccino, Enrico; Quinto, Ileana; Scala, Giuseppe] Magna Graecia Univ Catanzaro, Dept Expt & Clin Med, Catanzaro, Italy.
[Galandrini, Ricciarda; Capuano, Cristina] Univ Roma La Sapienza, Dept Expt Med, Rome, Italy.
[Santoni, Angela] Univ Roma La Sapienza, Fdn Cenci Bolognetti, Ist Pasteur, Dept Mol Med, Rome, Italy.
[Dal Piaz, Fabrizio] Univ Salerno, Dept Pharm, I-84100 Salerno, Italy.
[Venzon, David] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA.
RP Tuccillo, FM (reprint author), IRCCS, Ist Nazl Studio & Cura Tumori Fdn G Pascale, Lab Mol Biol & Viral Oncogenesis, Via Mariano Semmola, I-80131 Naples, Italy.
EM f.tuccillo@istitutotumori.na.it; quinto@unicz.it
RI Buonaguro, Franco/A-1964-2008; Iaccino, Enrico/I-7333-2015; santoni,
angela/K-8997-2016; Palmieri, Camillo/A-3195-2009;
OI Buonaguro, Franco/0000-0002-7491-7220; Iaccino,
Enrico/0000-0002-3565-7817; santoni, angela/0000-0003-1206-7731;
Palmieri, Camillo/0000-0001-6707-4723; D'ARMIENTO, Francesco
Paolo/0000-0002-1391-6451; CAPUANO, Cristina/0000-0002-6747-3836;
Barbieri, Antonio/0000-0002-7788-6167; FIUME,
Giuseppe/0000-0002-5414-6190; Arra, Claudio/0000-0003-3162-2091
FU Intramural NIH HHS [Z99 CA999999]
NR 50
TC 7
Z9 7
U1 1
U2 9
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1535-7163
EI 1538-8514
J9 MOL CANCER THER
JI Mol. Cancer Ther.
PD MAR
PY 2014
VL 13
IS 3
BP 752
EP 762
DI 10.1158/1535-7163.MCT-13-0651
PG 11
WC Oncology
SC Oncology
GA AE9HU
UT WOS:000334318300019
PM 24356816
ER
PT J
AU Smith, MA
AF Smith, Malcolm A.
TI Sorafenib Inhibits ABCG2 and Overcomes Irinotecan Resistance-Letter
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Letter
ID CANCER
C1 NCI, Bethesda, MD 20892 USA.
RP Smith, MA (reprint author), NCI, 9609 Med Ctr Dr,Room 5-W414,MSC 9737, Bethesda, MD 20892 USA.
EM Malcolm.Smith@nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 3
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 1535-7163
EI 1538-8514
J9 MOL CANCER THER
JI Mol. Cancer Ther.
PD MAR
PY 2014
VL 13
IS 3
BP 763
EP 763
DI 10.1158/1535-7163.MCT-13-0968
PG 1
WC Oncology
SC Oncology
GA AE9HU
UT WOS:000334318300020
PM 24615774
ER
PT J
AU Oelstrom, K
Goldschen-Ohm, MP
Holmgren, M
Chanda, B
AF Oelstrom, Kevin
Goldschen-Ohm, Marcel P.
Holmgren, Miguel
Chanda, Baron
TI Evolutionarily conserved intracellular gate of voltage-dependent sodium
channels
SO NATURE COMMUNICATIONS
LA English
DT Article
ID MULTIPLE SEQUENCE ALIGNMENT; CRYSTAL-STRUCTURE; K+ CHANNEL; NA+-CHANNEL;
BK CHANNELS; PORE; DOMAIN; INACTIVATION; ACTIVATION; RESIDUES
AB Members of the voltage-gated ion channel superfamily (VGIC) regulate ion flux and generate electrical signals in excitable cells by opening and closing pore gates. The location of the gate in voltage-gated sodium channels, a founding member of this superfamily, remains unresolved. Here we explore the chemical modification rates of introduced cysteines along the S6 helix of domain IV in an inactivation-removed background. We find that state-dependent accessibility is demarcated by an S6 hydrophobic residue; substituted cysteines above this site are not modified by charged thiol reagents when the channel is closed. These accessibilities are consistent with those inferred from open-and closed-state structures of prokaryotic sodium channels. Our findings suggest that an intracellular gate composed of a ring of hydrophobic residues is not only responsible for regulating access to the pore of sodium channels, but is also a conserved feature within canonical members of the VGIC superfamily.
C1 [Oelstrom, Kevin; Goldschen-Ohm, Marcel P.; Chanda, Baron] Univ Wisconsin, Dept Neurosci, Madison, WI 53706 USA.
[Oelstrom, Kevin] Univ Wisconsin, Mol Pharmacol Grad Program, Madison, WI 53706 USA.
[Holmgren, Miguel] NINDS, Mol Neurophysiol Sect, NIH, Bethesda, MD 20892 USA.
RP Chanda, B (reprint author), Univ Wisconsin, Dept Neurosci, Madison, WI 53706 USA.
EM chanda@wisc.edu
OI Chanda, Baron/0000-0003-4954-7034
FU NIH [GM084140]; Shaw Scientist Award; American Heart Association
[12POST9440021]; Translational Cardiovascular predoctoral training grant
[T32-HL07936]; Molecular and Cellular Pharmacology training grant
[T32GM008668]; National Institutes of Health (NIH), National Institute
of Neurological Disorders and Stroke
FX This project was supported by Research grants from NIH GM084140 and Shaw
Scientist Award to B. C., the American Heart Association (Midwest
Affiliate) Postdoctoral fellowship (12POST9440021) to M.P.G.-O. and
Translational Cardiovascular predoctoral training grant (T32-HL07936)
and Molecular and Cellular Pharmacology training grant (T32GM008668) to
K.O. M. H. was supported by the intramural section of the National
Institutes of Health (NIH), National Institute of Neurological Disorders
and Stroke. We thank Dorothy Hanck (University of Chicago) and John Kyle
(UW-Madison) for their generous gift of the sodium channel cysteine
mutants S1578C-L1591C as well as Sandipan Chowdhury and Dr Brian Jarecki
for useful discussions.
NR 37
TC 12
Z9 12
U1 0
U2 18
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD MAR
PY 2014
VL 5
AR 3420
DI 10.1038/ncomms4420
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AE9CA
UT WOS:000334300400003
PM 24619022
ER
PT J
AU Cohn, A
Hagman, BT
Moore, K
Mitchell, J
Ehlke, S
AF Cohn, Amy
Hagman, Brett T.
Moore, Kathleen
Mitchell, Jessica
Ehlke, Sarah
TI Does Negative Affect Mediate the Relationship Between Daily PTSD
Symptoms and Daily Alcohol Involvement in Female Rape Victims? Evidence
From 14 Days of Interactive Voice Response Assessment
SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS
LA English
DT Article
DE rape; alcohol; interactive voice response; daily diary; PTSD; negative
affect
ID POSTTRAUMATIC-STRESS-DISORDER; ECOLOGICAL MOMENTARY ASSESSMENT; SEXUAL
ASSAULT SURVIVORS; SELF-MEDICATION HYPOTHESIS; TRAUMA-EXPOSED ADULTS;
SUBSTANCE USE; PSYCHOMETRIC PROPERTIES; TREATED ALCOHOLICS;
COLLEGE-STUDENTS; MOOD DISORDERS
AB The negative reinforcement model of addiction posits that individuals may use alcohol to reduce negative affective (NA) distress. The current study investigated the mediating effect of daily NA on the relationship between daily PTSD symptoms and same-day and next-day alcohol involvement (consumption and desire to drink) in a sample of 54 non-treatment-seeking female rape victims who completed 14 days of interactive voice response assessment. The moderating effect of lifetime alcohol use disorder diagnosis (AUD) on daily relationships was also examined. Multilevel models suggested that NA mediated the relationship between PTSD and same-day, but not next-day alcohol involvement. NA was greater on days characterized by more severe PTSD symptoms, and alcohol consumption and desire to drink were greater on days characterized by higher NA. Furthermore, daily PTSD symptoms and NA were more strongly associated with same-day (but not next-day) alcohol consumption and desire to drink for women with an AUD than without. Results suggest that NA plays an important role in female rape victims' daily alcohol use. Differences between women with and without an AUD indicate the need for treatment matching to subtypes of female rape victims.
C1 [Cohn, Amy; Moore, Kathleen; Mitchell, Jessica] Univ S Florida, Dept Mental Hlth Law & Policy, Tampa, FL 33620 USA.
[Hagman, Brett T.] Natl Inst Alcohol Abuse & Alcoholism, Bethesda, MD USA.
[Ehlke, Sarah] Univ N Carolina, Dept Psychol, Wilmington, NC USA.
RP Cohn, A (reprint author), Amer Legacy Fdn, Schroeder Inst Tobacco Res & Policy Studies, 1724 Massachusetts Ave NW, Washington, DC 20036 USA.
EM acohn@legacyforhealth.org
FU NIDA NIH HHS [P30 DA028807, P30DA028807]
NR 102
TC 6
Z9 6
U1 11
U2 19
PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA
SN 0893-164X
EI 1939-1501
J9 PSYCHOL ADDICT BEHAV
JI Psychol. Addict. Behav.
PD MAR
PY 2014
VL 28
IS 1
BP 114
EP 126
DI 10.1037/a0035725
PG 13
WC Substance Abuse; Psychology, Multidisciplinary
SC Substance Abuse; Psychology
GA AF4OR
UT WOS:000334693600013
PM 24731112
ER
PT J
AU Robinson, CD
Pickworth, WB
Heishman, SJ
Waters, AJ
AF Robinson, Cendrine D.
Pickworth, Wallace B.
Heishman, Stephen J.
Waters, Andrew J.
TI The Acute Tobacco Withdrawal Syndrome Among Black Smokers
SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS
LA English
DT Article
DE tobacco; race; menthol; health disparities; withdrawal
ID FAGERSTROM TOLERANCE QUESTIONNAIRE; NICOTINE REPLACEMENT THERAPY;
SMOKING-CESSATION TRIALS; CIGARETTE SMOKERS; WHITE SMOKERS;
RACIAL/ETHNIC DISPARITIES; MENTHOLATED CIGARETTES; ETHNIC DISPARITIES;
AFRICAN-AMERICAN; NATIONAL-HEALTH
AB Black smokers have greater difficulty quitting tobacco than White smokers, but the mechanisms underlying between-race differences in smoking cessation are not clear. One possibility is that Black smokers experience greater acute withdrawal than Whites. We investigated whether Black (n = 104) and White smokers (n = 99) differed in abstinence-induced changes in self-report, physiological, and cognitive performance measures. Smokers not wishing to quit completed two counterbalanced experimental sessions. Before one session, they abstained from smoking for at least 12 hr. They smoked normally before the other session. Black smokers reported smaller abstinence-induced changes on a number of subjective measures including the total score of the 10-item Questionnaire for Smoking Urges (QSU) and the total score of the Wisconsin Smoking Withdrawal Scale (WSWS). However, on most subjective measures, and on all objective measures, there were no between-race differences in abstinence-induced change scores. Moreover, Black participants did not report lower QSU and WSWS ratings at the abstinent session, but they did experience significantly higher QSU and WSWS ratings at the nonabstinent session. Abstinence-induced changes in subjective, physiological, and cognitive measures in White smokers were similar for smokers of nonflavored and menthol-flavored cigarettes. There was no evidence that Black smokers experienced greater acute tobacco withdrawal than Whites. To the contrary, Black participants experienced smaller abstinence-induced changes in self-reported craving and withdrawal on some measures. Racial differences in smoking cessation are unlikely to be explained by acute withdrawal.
C1 [Robinson, Cendrine D.; Waters, Andrew J.] Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, Bethesda, MD 20814 USA.
[Pickworth, Wallace B.] Battelle Ctr Publ Hlth Res & Evaluat, Baltimore, MD USA.
[Heishman, Stephen J.] NIDA, Nicotine Psychopharmacol Sect, Intramural Res Program, Baltimore, MD USA.
RP Robinson, CD (reprint author), Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM crobinson@usuhs.edu
FU Intramural NIH HHS
NR 60
TC 5
Z9 5
U1 5
U2 8
PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA
SN 0893-164X
EI 1939-1501
J9 PSYCHOL ADDICT BEHAV
JI Psychol. Addict. Behav.
PD MAR
PY 2014
VL 28
IS 1
BP 173
EP 181
DI 10.1037/a0031950
PG 9
WC Substance Abuse; Psychology, Multidisciplinary
SC Substance Abuse; Psychology
GA AF4OR
UT WOS:000334693600019
PM 23528199
ER
PT J
AU Koonin, EV
AF Koonin, Eugene V.
TI Carl Woese's vision of cellular evolution and the domains of life
SO RNA BIOLOGY
LA English
DT Review
DE evolutionary transitions; domains of life; cellular evolution; Darwinian
threshold; progenote; horizontal gene transfer
ID HORIZONTAL GENE-TRANSFER; BACTERIAL PAN-GENOME; PROTEIN EVOLUTION;
MICROBIAL WORLD; UNIVERSAL TREE; SCALING LAWS; VIRUS WORLD; RNA WORLD;
ORIGIN; CELLS
AB In a series of conceptual articles published around the millennium, Carl Woese emphasized that evolution of cells is the central problem of evolutionary biology, that the three-domain ribosomal tree of life is an essential framework for reconstructing cellular evolution, and that the evolutionary dynamics of functionally distinct cellular systems are fundamentally different, with the information processing systems "crystallizing" earlier than operational systems. The advances of evolutionary genomics over the last decade vindicate major aspects of Woese's vision. Despite the observations of pervasive horizontal gene transfer among bacteria and archaea, the ribosomal tree of life comes across as a central statistical trend in the "forest" of phylogenetic trees of individual genes, and hence, an appropriate scaffold for evolutionary reconstruction. The evolutionary stability of information processing systems, primarily translation, becomes ever more striking with the accumulation of comparative genomic data indicating that nearly all of the few universal genes encode translation system components. Woese's view on the fundamental distinctions between the three domains of cellular life also withstand the test of comparative genomics, although his non-acceptance of symbiogenetic scenarios for the origin of eukaryotes might not. Above all, Woese's key prediction that understanding evolution of microbes will be the core of the new evolutionary biology appears to be materializing.
C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
EM koonin@ncbi.nlm.nih.gov
FU US Department of Health and Human Resources
FX E.V.K. is supported by intramural funds of the US Department of Health
and Human Resources (to the National Library of Medicine, NIH).
NR 78
TC 9
Z9 10
U1 1
U2 49
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1547-6286
EI 1555-8584
J9 RNA BIOL
JI RNA Biol.
PD MAR 1
PY 2014
VL 11
IS 3
BP 197
EP 204
DI 10.4161/rna.27673
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AF8XR
UT WOS:000334999500006
PM 24572480
ER
PT J
AU Dasgupta, A
Szymczak, S
Moore, JH
Bailey-Wilson, JE
Malley, JD
AF Dasgupta, Abhijit
Szymczak, Silke
Moore, Jason H.
Bailey-Wilson, Joan E.
Malley, James D.
TI Risk estimation using probability machines
SO BIODATA MINING
LA English
DT Article
DE Consistent nonparametric regression; Logistic regression; Probability;
machine; Odds ratio; Counterfactuals; Interactions
ID RANDOM FORESTS
AB Background: Logistic regression has been the de facto, and often the only, model used in the description and analysis of relationships between a binary outcome and observed features. It is widely used to obtain the conditional probabilities of the outcome given predictors, as well as predictor effect size estimates using conditional odds ratios.
Results: We show how statistical learning machines for binary outcomes, provably consistent for the nonparametric regression problem, can be used to provide both consistent conditional probability estimation and conditional effect size estimates. Effect size estimates from learning machines leverage our understanding of counterfactual arguments central to the interpretation of such estimates. We show that, if the data generating model is logistic, we can recover accurate probability predictions and effect size estimates with nearly the same efficiency as a correct logistic model, both for main effects and interactions. We also propose a method using learning machines to scan for possible interaction effects quickly and efficiently. Simulations using random forest probability machines are presented.
Conclusions: The models we propose make no assumptions about the data structure, and capture the patterns in the data by just specifying the predictors involved and not any particular model structure. So they do not run the same risks of model mis-specification and the resultant estimation biases as a logistic model. This methodology, which we call a "risk machine", will share properties from the statistical machine that it is derived from.
C1 [Dasgupta, Abhijit] NIAMSD, Clin Trials & Outcomes Branch, NIH, Bethesda, MD 20892 USA.
[Szymczak, Silke; Bailey-Wilson, Joan E.] NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD 21224 USA.
[Moore, Jason H.] Dartmouth Coll, Hitchcock Med Ctr, Dept Genet, Lebanon, NH 03756 USA.
[Malley, James D.] NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA.
RP Dasgupta, A (reprint author), NIAMSD, Clin Trials & Outcomes Branch, NIH, Room 4-1350,Bldg 10 CRC,10 Ctr Dr, Bethesda, MD 20892 USA.
EM abhijit.dasgupta@nih.gov
RI Szymczak, Silke/C-6625-2013;
OI Bailey-Wilson, Joan/0000-0002-9153-2920
FU Intramural Research Programs of the National Institute of Arthritis,
Musculoskeletal and Skin Disorders; National Human Genome Research
Institute; Center for Information Technology, National Institutes of
Health; NIH [LM009012]
FX This project was supported by the Intramural Research Programs of the
National Institute of Arthritis, Musculoskeletal and Skin Disorders
(AD), the National Human Genome Research Institute (SS, JEBW), and the
Center for