FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Mohiuddin, MM
Singh, AK
Corcoran, PC
Hoyt, RF
Thomas, ML
Lewis, BGT
Eckhaus, M
Reimann, KA
Klymiuk, N
Wolf, E
Ayares, D
Horvath, KA
AF Mohiuddin, M. M.
Singh, A. K.
Corcoran, P. C.
Hoyt, R. F.
Thomas, M. L., III
Lewis, B. G. T.
Eckhaus, M.
Reimann, K. A.
Klymiuk, N.
Wolf, E.
Ayares, D.
Horvath, K. A.
TI One-Year Heterotopic Cardiac Xenograft Survival in a Pig to Baboon Model
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Letter
C1 [Mohiuddin, M. M.; Singh, A. K.; Corcoran, P. C.; Horvath, K. A.] NHLBI, Cardiothorac Surg Res Program, NIH, Bethesda, MD 20892 USA.
[Hoyt, R. F.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Thomas, M. L., III; Lewis, B. G. T.; Eckhaus, M.] NIH, Div Vet Resources, ORS, Bethesda, MD 20892 USA.
[Reimann, K. A.] Univ Massachusetts, MassBiol, Boston, MA 02125 USA.
[Klymiuk, N.; Wolf, E.] Univ Munich, Inst Mol Anim Breeding & Biotechnol, Munich, Germany.
[Ayares, D.] Revivicor Inc, Blacksburg, VA USA.
RP Mohiuddin, MM (reprint author), NHLBI, Cardiothorac Surg Res Program, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM mohiuddinm@mail.nih.gov
RI Mohiuddin, Muhammad/M-4642-2013;
OI Mohiuddin, Muhammad/0000-0003-4654-783X; Wolf,
Eckhard/0000-0002-0430-9510
FU NHLBI NIH HHS [HHSN268201300001C]; NIAID NIH HHS [U24 AI126683]
NR 5
TC 36
Z9 36
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1600-6135
EI 1600-6143
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD FEB
PY 2014
VL 14
IS 2
BP 488
EP 489
DI 10.1111/ajt.12562
PG 2
WC Surgery; Transplantation
SC Surgery; Transplantation
GA 297OT
UT WOS:000330265500031
PM 24330419
ER
PT J
AU Chihara, D
Ito, H
Matsuda, T
Shibata, A
Katsumi, A
Nakamura, S
Tomotaka, S
Morton, LM
Weisenburger, DD
Matsuo, K
AF Chihara, Dai
Ito, Hidemi
Matsuda, Tomohiro
Shibata, Akiko
Katsumi, Akira
Nakamura, Shigeo
Tomotaka, Sobue
Morton, Lindsay M.
Weisenburger, Dennis D.
Matsuo, Keitaro
TI Differences in incidence and trends of haematological malignancies in
Japan and the United States
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE incidence; trend; haematological malignancies; surveillance epidemiology
and end results; Japan
ID NON-HODGKIN-LYMPHOMA; POOLED ANALYSIS; LEUKEMIA INCIDENCE;
GENETIC-VARIATION; CANCER REGISTRY; RISK; POPULATION; PATTERNS;
IMMUNODEFICIENCY; SUBTYPES
AB The incidence of a malignant disease reflects the genetic and cumulative exposure to the environment of a population. Therefore, evaluation of the incidence and trends of a disease in different populations may provide insights into its aetiology and pathogenesis. To evaluate the incidence of haematological malignancies according to specific subtypes, we used population-based registry data in Japan (N=125148) and the United States (US; N=172925) from 1993 to 2008. The age-adjusted incidence of haematological malignancies in Japan was approximately one-half that in the US but has been increasing significantly, whereas no significant change was seen in the US [annual percent change (95% C confidence interval): Japan, +24% (17, 31); US, +01% (-01, 02)]. Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) showed the largest differences in incidence, with the most remarkable differences observed for chronic lymphocytic leukaemia, HL-nodular sclerosis, mycosis fungoides and cutaneous T-cell lymphoma. HL and NHL are increasing substantially in Japan but not in the US, suggesting that environmental exposures, such as Westernization of the life style may be causing this increase. Differences in the incidence and trends for specific subtypes also showed a marked contrast across subtypes, which, in turn, may provide significant new insights into disease aetiology in the future.
C1 [Chihara, Dai; Ito, Hidemi; Matsuo, Keitaro] Aichi Canc Ctr Res Inst, Div Epidemiol & Prevent, Nagoya, Aichi, Japan.
[Matsuda, Tomohiro; Shibata, Akiko] Natl Canc Ctr, Ctr Canc Control & Informat Serv, Surveillance Div, Tokyo 104, Japan.
[Katsumi, Akira] Hamamatsu Univ Sch Med, Dept Clin Oncol, Hamamatsu, Shizuoka 4313192, Japan.
[Nakamura, Shigeo] Nagoya Univ, Grad Sch Med, Dept Pathol, Nagoya, Aichi 4648601, Japan.
[Tomotaka, Sobue] Osaka Univ, Grad Sch Med, Dept Environm Med & Populat Sci, Osaka, Japan.
[Morton, Lindsay M.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD USA.
[Weisenburger, Dennis D.] City Hope Natl Med Ctr, Dept Pathol, Duarte, CA 91010 USA.
[Matsuo, Keitaro] Kyushu Univ, Fac Med Sci, Dept Prevent Med, Fukuoka 812, Japan.
RP Matsuo, K (reprint author), Kyushu Univ, Fac Med Sci, Dept Prevent Med, Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan.
EM keitarom@med.kyushu-u.ac.jp
RI Nakamura, Shigeo/I-1571-2012; Morton, Lindsay/B-5234-2015; U-ID,
Kyushu/C-5291-2016;
OI Morton, Lindsay/0000-0001-9767-2310; Matsuo, Keitaro/0000-0003-1761-6314
FU 3rd-term Comprehensive 10-year Strategy for Cancer Control; National
Centre for Geriatrics and Gerontology (NCGG), Japan [22-9]; Takeda
Science Foundation
FX We thank all of the registries included in this analysis, and the staff
of the MCIJ and SEER projects. This study was supported by the 3rd-term
Comprehensive 10-year Strategy for Cancer Control and by the Research
Funding for Longevity Sciences (22-9) from the National Centre for
Geriatrics and Gerontology (NCGG), Japan and partly supported by a grant
from Takeda Science Foundation.
NR 37
TC 40
Z9 40
U1 1
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-1048
EI 1365-2141
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD FEB
PY 2014
VL 164
IS 4
BP 536
EP 545
DI 10.1111/bjh.12659
PG 10
WC Hematology
SC Hematology
GA 295MN
UT WOS:000330120300008
PM 24245986
ER
PT J
AU Wang, XS
Zhao, FM
Fisch, MJ
O'Mara, AM
Cella, D
Mendoza, TR
Cleeland, CS
AF Wang, Xin Shelley
Zhao, Fengmin
Fisch, Michael J.
O'Mara, Ann M.
Cella, David
Mendoza, Tito R.
Cleeland, Charles S.
TI Prevalence and Characteristics of Moderate To Severe Fatigue
SO CANCER
LA English
DT Article
DE fatigue; patient-reported outcome; practice guidelines; M. D. Anderson
Symptom Inventory (MDASI); survivorship
ID CANCER-RELATED FATIGUE; CUT-POINTS; DOUBLE-BLIND; PAIN; SURVIVORS;
SYMPTOMS; MILD; INTERFERENCE; INVENTORY; IMPACT
AB BACKGROUNDThe effective management of fatigue in patients with cancer requires a clear delineation of what constitutes nontrivial fatigue. The authors defined numeric cutpoints for fatigue severity based on functional interference and described the prevalence and characteristics of fatigue in patients with cancer and survivors.
METHODSIn a multicenter study, outpatients with breast, prostate, colorectal, or lung cancer rated their fatigue severity and symptom interference with functioning on the M. D. Anderson Symptom Inventory numeric scale of 0 to 10. Ratings of symptom interference guided the selection of numeric rating cutpoints between mild, moderate, and severe fatigue levels. Regression analysis identified significant factors related to reporting moderate/severe fatigue.
RESULTSThe statistically optimal cutpoints were 4 for moderate fatigue and 7 for severe fatigue. Moderate/severe fatigue was reported by 983 of 2177 patients (45%) undergoing active treatment and was more likely to occur in patients receiving treatment with strong opioids (odds ratio [OR], 3.00), those with a poor Eastern Cooperative Oncology Group performance status (OR, 2.00), those who had >5% weight loss within 6 months (OR, 1.60), those who were receiving >10 medications (OR, 1.58), those with lung cancer (OR, 1.55), and those with a history of depression (OR, 1.42). Among survivors (patients with complete remission or no evidence of disease, and not currently receiving cancer treatment), 29% of patients (150 of 515 patients) had moderate/severe fatigue that was associated with poor performance status (OR, 3.48) and a history of depression (OR, 2.21).
CONCLUSIONSThe current study statistically defined fatigue severity categories related to significantly increased symptom interference. The high prevalence of moderate/severe fatigue in both actively treated patients with cancer and survivors warrants the promoting of the routine assessment and management of patient-reported fatigue. Cancer 2014;120:425-432. (c) 2013 American Cancer Society.
C1 [Wang, Xin Shelley; Mendoza, Tito R.; Cleeland, Charles S.] Univ Texas MD Anderson Canc Ctr, Dept Symptom Res, Houston, TX 77030 USA.
[Zhao, Fengmin] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Fisch, Michael J.] Univ Texas MD Anderson Canc Ctr, Dept Gen Oncol, Houston, TX 77030 USA.
[O'Mara, Ann M.] NCI, Community Oncol & Prevent Trials Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA.
[Cella, David] Northwestern Univ, Dept Med Social Sci, Chicago, IL 60611 USA.
RP Wang, XS (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Symptom Res, 1515 Holcombe Blvd,Unit 1450, Houston, TX 77030 USA.
EM xswang@mdanderson.org
FU National Cancer Institute of the National Institutes of Health [U10
CA37403, U10 CA17145]; Eastern Cooperative Oncology Group [R01
CA026582]; University of Texas MD Anderson Cancer Center Support [P30
CA016672]
FX Supported in part by grants from the National Cancer Institute of the
National Institutes of Health, including U10 CA37403 and U10 CA17145 to
the Eastern Cooperative Oncology Group; R01 CA026582 to Dr. Cleeland (
Principal Investigator); and The University of Texas MD Anderson Cancer
Center Support Grant P30 CA016672 to R.A. DePinho ( Principal
Investigator).
NR 29
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Z9 33
U1 0
U2 15
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 FEB 1
PY 2014
VL 120
IS 3
BP 425
EP 432
DI 10.1002/cncr.28434
PG 8
WC Oncology
SC Oncology
GA 297PP
UT WOS:000330267700016
PM 24436136
ER
PT J
AU Fisch, MJ
Zhao, F
O'Mara, AM
Wang, XS
Cella, D
Cleeland, CS
AF Fisch, Michael J.
Zhao, Fengmin
O'Mara, Ann M.
Wang, Xin Shelley
Cella, David
Cleeland, Charles S.
TI Predictors of Significant Worsening of Patient-Reported Fatigue Over a
1-Month Timeframe in Ambulatory Patients With Common Solid Tumors
SO CANCER
LA English
DT Article
DE cancer fatigue; symptom management; medical oncology; ambulatory care
ID CANCER-RELATED FATIGUE; PLACEBO-CONTROLLED TRIAL; CLINICALLY SIGNIFICANT
FATIGUE; RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; BREAST-CANCER;
DOUBLE-BLIND; RADIATION-THERAPY; ADJUVANT THERAPY; WOMEN
AB BACKGROUNDUnderstanding the determinants of fatigue worsening may help distinguish between different fatigue phenotypes and inform clinical trial designs.
METHODSPatients with invasive cancer of the breast, prostate, colon/rectum, or lung were enrolled from multiple sites. At enrollment during an outpatient visit and 4 or 5 weeks later, patients rated their symptoms on a numerical rating scale from zero to 10. A 2-point change on that scale was considered clinically significant for a change in fatigue. Effects of demographic and clinical factors on patient-reported fatigue were examined using logistic regression models.
RESULTSIn total, 3123 patients were enrolled at baseline, and 3032 patients could be analyzed for fatigue change. At baseline, 23% of patients had no fatigue, 35% had mild fatigue, 25% had moderate fatigue, and 17% had severe fatigue. Key parameters in a model of fatigue worsening included fatigue at baseline (odds ratio [OR], 0.75), disease status (OR, 1.99), performance status (OR, 1.38), history of depression (OR, 1.28), patient perception of bother because of comorbidity (OR, 1.26), and treatment exposures, including recent cancer treatment (OR, 1.77) and receipt of corticosteroids (OR, 1.37). The impact of sex was examined only in patients with colorectal and lung cancer, and it was a significant factor, with men most likely to experience worsening of fatigue (OR, 1.46).
CONCLUSIONSPredictors of fatigue worsening included multiple factors that were difficult to modify, including the baseline fatigue level, sex, disease status, performance status, recent cancer treatment, bother because of comorbidity, and history of depression. Future fatigue prevention and treatment trial designs should account for key predictors of worsening fatigue. Cancer 2014;120:442-450 (c) 2013 American Cancer Society.
C1 [Fisch, Michael J.] Univ Texas MD Anderson Canc Ctr, Dept Gen Oncol, Houston, TX 77030 USA.
[Zhao, Fengmin] Dana Farber Canc Inst, Boston, MA 02115 USA.
[O'Mara, Ann M.] NCI, Bethesda, MD 20892 USA.
[Cella, David] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Wang, Xin Shelley; Cleeland, Charles S.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
RP Fisch, MJ (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Gen Oncol, Unit 410,1515 Holcombe Blvd, Houston, TX 77030 USA.
EM mfisch@mdanderson.org
FU National Cancer Institute of the National Institutes of Health [U10
CA37403, U10 CA17145, R01 CA026582]
FX This study was supported in part by grants from the National Cancer
Institute of the National Institutes of Health, including grants U10
CA37403 and U10 CA17145 to the Eastern Cooperative Oncology Group and
grant R01 CA026582 to C.S.C.
NR 47
TC 4
Z9 4
U1 2
U2 14
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 FEB 1
PY 2014
VL 120
IS 3
BP 442
EP 450
DI 10.1002/cncr.28437
PG 9
WC Oncology
SC Oncology
GA 297PP
UT WOS:000330267700018
PM 24151111
ER
PT J
AU Nachman, S
Zheng, N
Acosta, EP
Teppler, H
Homony, B
Graham, B
Fenton, T
Xu, X
Wenning, L
Spector, SA
Frenkel, LM
Alvero, C
Worrell, C
Handelsman, E
Wiznia, A
AF Nachman, Sharon
Zheng, Nan
Acosta, Edward P.
Teppler, Hedy
Homony, Brenda
Graham, Bobbie
Fenton, Terence
Xu, Xia
Wenning, Larissa
Spector, Stephen A.
Frenkel, Lisa M.
Alvero, Carmelita
Worrell, Carol
Handelsman, Edward
Wiznia, Andrew
CA Int Maternal Pediat Adolescent
TI Pharmacokinetics, Safety, and 48-Week Efficacy of Oral Raltegravir in
HIV-1-Infected Children Aged 2 Through 18 Years
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
DE pediatric HIV; raltegravir; pharmacokinetics; adverse event
ID OPTIMIZED BACKGROUND THERAPY; HIV-1 INFECTION; HUMAN PLASMA; ADOLESCENTS
AB Background. IMPAACT P1066 is a phase I/II open-label multicenter trial to evaluate pharmacokinetics, safety, tolerability, and efficacy of multiple raltegravir formulations in human immunodeficiency virus (HIV)-infected youth.
Methods. Dose selection for each cohort (I: 12 to <19 years; II: 6 to <12 years; and III: 2 to <6 years) was based on review of short-term safety (4 weeks) and intensive pharmacokinetic evaluation. Safety data through weeks 24 and 48, and grade >= 3 or serious adverse events (AEs) were assessed. The primary virologic endpoint was achieving HIV RNA <400 copies/mL or >= 1 log(10) reduction between baseline and week 24.
Results. The targeted pharmacokinetic parameters (AUC(0-12h) and C-12h) were achieved for each cohort, allowing dose selection for 2 formulations. Of 96 final dose subjects, there were 15 subjects with grade 3 or higher clinical AEs (1 subject with drug-related [DR] psychomotor hyperactivity and insomnia); 16 subjects with grade 3 or higher laboratory AEs (1 with DR transaminase elevation); 14 subjects with serious clinical AEs (1 with DR rash); and 1 subjects with serious laboratory AEs (1 with DR transaminase increased). There were no discontinuations due to AEs and no DR deaths. Favorable virologic responses at week 48 were observed in 79.1% of patients, with a mean CD4 increase of 156 cells/mu L (4.6%).
Conclusions. Raltegravir as a film-coated tablet 400 mg twice daily (6 to < 19 years, and >= 25 kg) and chewable tablet 6 mg/kg (maximum dose 300 mg) twice daily (2 to < 12 years) was well tolerated and showed favorable virologic and immunologic responses.
Clinical Trials Registration NCT00485264.
C1 [Nachman, Sharon] SUNY Stony Brook, Dept Pediat, Stony Brook, NY 11794 USA.
[Zheng, Nan; Fenton, Terence; Alvero, Carmelita] Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA.
[Acosta, Edward P.] Univ Alabama Birmingham, Div Clin Pharmacol, Birmingham, AL USA.
[Teppler, Hedy; Homony, Brenda; Xu, Xia; Wenning, Larissa] Merck & Co Inc, West Point, PA USA.
[Graham, Bobbie] Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA.
[Spector, Stephen A.] Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA.
[Spector, Stephen A.] Rady Childrens Hosp San Diego, La Jolla, CA USA.
[Frenkel, Lisa M.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA.
[Frenkel, Lisa M.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA.
[Frenkel, Lisa M.] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA.
[Frenkel, Lisa M.] Seattle Childrens Hosp & Res Inst, Seattle, WA USA.
[Worrell, Carol] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal & Pediat Infect Dis Branch, Bethesda, MD USA.
[Handelsman, Edward] NIAID, Div AIDS, NIH, Bethesda, MD 20892 USA.
[Wiznia, Andrew] Jacobi Med Ctr, Bronx, NY USA.
RP Nachman, S (reprint author), SUNY Stony Brook, Dept Pediat, Hlth Sci Ctr, T11-031, Stony Brook, NY 11794 USA.
EM sharon.nachman@stonybrook.edu
OI Frenkel, Lisa M/0000-0001-9566-8959
FU NIAID [U01 AI068632]; NICHD; National Institute of Mental Health
[AI068632]; Statistical and Data Analysis Center at Harvard School of
Public Health, under the NIAID [5 U01 AI41110]; Pediatric AIDS Clinical
Trials Group; IMPAACT Group [1 U01 AI068616]; NIAID; NICHD International
and Domestic Pediatric and Maternal HIV Clinical Trials Network; NICHD
[N01-DK-9-001/HHSN267200800001C]; Merck Co Inc.
FX Overall support for the IMPAACT Group was provided by the NIAID (grant
number U01 AI068632), the NICHD, and the National Institute of Mental
Health (grant number AI068632). The content is solely the responsibility
of the authors and does not necessarily represent the official views of
the NIH. This work was supported by the Statistical and Data Analysis
Center at Harvard School of Public Health, under the NIAID cooperative
agreement 5 U01 AI41110 with the Pediatric AIDS Clinical Trials Group
and 1 U01 AI068616 with the IMPAACT Group. Support of the sites was
provided by the NIAID and the NICHD International and Domestic Pediatric
and Maternal HIV Clinical Trials Network funded by NICHD (contract
number N01-DK-9-001/HHSN267200800001C), and by Merck & Co Inc.
NR 9
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U1 1
U2 2
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 FEB 1
PY 2014
VL 58
IS 3
BP 413
EP 422
DI 10.1093/cid/cit696
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 300AD
UT WOS:000330435900019
PM 24145879
ER
PT J
AU Wellman, CL
Camp, M
Jones, VM
MacPherson, KP
Ihne, J
Fitzgerald, P
Maroun, M
Drabant, E
Bogdan, R
Hariri, AR
Holmes, A
AF Wellman, Cara L.
Camp, Marguerite
Jones, V. Morgan
MacPherson, Kathryn P.
Ihne, Jessica
Fitzgerald, Paul
Maroun, Mouna
Drabant, Emily
Bogdan, Ryan
Hariri, Ahmad R.
Holmes, Andrew
TI Convergent effects of mouse Pet-1 deletion and human PET-1 variation on
amygdala fear and threat processing (vol 250, pg 260, 2013)
SO EXPERIMENTAL NEUROLOGY
LA English
DT Correction
C1 [Wellman, Cara L.; Jones, V. Morgan] Indiana Univ, Ctr Integrat Study Anim Behav, Dept Psychol & Brain Sci, Bloomington, IN 47405 USA.
[Camp, Marguerite; MacPherson, Kathryn P.; Ihne, Jessica; Fitzgerald, Paul; Holmes, Andrew] NIAAA, Lab Behav & Genom Neurosci, NIH, Bethesda, MD USA.
[Maroun, Mouna] Univ Haifa, Fac Nat Sci, Dept Neurobiol, IL-31999 Haifa, Israel.
[Drabant, Emily] 23andMe, Mountain View, CA USA.
[Bogdan, Ryan; Hariri, Ahmad R.] Duke Univ, Inst Genome Sci & Policy, Dept Psychol & Neurosci, Neurogenet Lab, Durham, NC USA.
RP Wellman, CL (reprint author), Indiana Univ, 1101 E 10th St, Bloomington, IN 47405 USA.
EM wellmanc@indiana.edu
NR 1
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4886
EI 1090-2430
J9 EXP NEUROL
JI Exp. Neurol.
PD FEB
PY 2014
VL 252
BP 104
EP 104
DI 10.1016/j.expneurol.2013.11.002
PG 1
WC Neurosciences
SC Neurosciences & Neurology
GA 299TW
UT WOS:000330419600012
ER
PT J
AU Aung, PP
Liu, YC
Ballester, LY
Robbins, PF
Rosenberg, SA
Lee, CCR
AF Aung, Phyu P.
Liu, Yen-Chun
Ballester, Leomar Y.
Robbins, Paul F.
Rosenberg, Steven A.
Lee, Chyi-Chia Richard
TI Expression of New York esophageal squamous cell carcinoma-1 in primary
and metastatic melanoma
SO HUMAN PATHOLOGY
LA English
DT Article
DE NY-ESO-1; Melanoma; Cancer testis antigen; Immunotherapy
ID CANCER-TESTIS ANTIGENS; IMMUNOTHERAPY; RESPONSES; DIAGNOSIS; THERAPY;
TUMORS
AB New York esophageal squamous cell carcinoma-1 (NY-ESO-1), a cancer testis antigen, is an ideal target for adoptive cell transfer immunotherapy. Evidence from several clinical trials in melanoma and other malignancies shows the potential value of targeting the NY-ESO-1 antigen in immune-based therapy of metastatic tumors. However, the incidence of NY-ESO-1 expression in metastatic melanoma is unknown, and thus, it is unclear how many patients might benefit from this therapy. In this study, we analyzed NY-ESO-1 expression in 222 melanoma specimens, including 16 primary and 206 metastatic tumors. Our results support previous fmdings showing higher expression of NY-ESO-1 in metastatic (58/206; 28.2%) versus primary (0/16) tumors. In addition, our results show that the epithelioid subtype of melanoma has the highest incidence of NY-ESO-1 expression. These findings provide evidence of the value of this specific adoptive cell transfer therapy for the treatment of metastatic melanoma. Published by Elsevier Inc.
C1 [Aung, Phyu P.; Liu, Yen-Chun; Ballester, Leomar Y.; Lee, Chyi-Chia Richard] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Robbins, Paul F.; Rosenberg, Steven A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
RP Lee, CCR (reprint author), NCI, Pathol Lab, NIH, 10 Ctr Dr,Room 2B50, Bethesda, MD 20892 USA.
EM leechy@mail.nih.gov
RI Lee, Chyi-Chia/I-1938-2013
OI Lee, Chyi-Chia/0000-0002-5306-7781
FU Intramural NIH HHS [Z99 CA999999]
NR 19
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U1 0
U2 1
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0046-8177
EI 1532-8392
J9 HUM PATHOL
JI Hum. Pathol.
PD FEB
PY 2014
VL 45
IS 2
BP 259
EP 267
DI 10.1016/j.humpath.2013.05.029
PG 9
WC Pathology
SC Pathology
GA 301SB
UT WOS:000330551300009
PM 24290058
ER
PT J
AU Chiang, D
Grishin, AV
Masilamani, M
Merad, M
Palucka, AK
Ueno, H
Burks, AW
Jones, SM
Liu, AH
Sicherer, SH
Wood, RA
Davidson, W
Sampson, HA
Berin, MC
AF Chiang, David
Grishin, Alexander V.
Masilamani, Madhan
Merad, Miriam
Palucka, A. Karolina
Ueno, Hideki
Burks, A. Wesley
Jones, Stacie M.
Liu, Andrew H.
Sicherer, Scott H.
Wood, Robert A.
Davidson, Wendy
Sampson, Hugh A.
Berin, M. Cecilia
TI Profile Of Food Allergen-Specific T Cells In Allergic and Clinically
Tolerant Individuals
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 28-MAR 04, 2014
CL San Diego, CA
SP Amer Acad Allergy Asthma & Immunol
C1 [Chiang, David; Grishin, Alexander V.; Masilamani, Madhan; Merad, Miriam; Palucka, A. Karolina; Sicherer, Scott H.; Berin, M. Cecilia] Mt Sinai, Icahn Sch Med, New York, NY USA.
[Palucka, A. Karolina; Ueno, Hideki] Baylor Inst Immunol Res, Dallas, TX USA.
[Burks, A. Wesley] Univ N Carolina, Chapel Hill, NC USA.
[Jones, Stacie M.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA.
[Jones, Stacie M.] Arkansas Childrens Hosp, Little Rock, AR 72202 USA.
[Liu, Andrew H.] Natl Jewish Hlth, Denver, CO USA.
[Wood, Robert A.] Johns Hopkins Univ, Med Ctr, Baltimore, MD 21218 USA.
[Davidson, Wendy] NIH, Bethesda, MD 20892 USA.
[Sampson, Hugh A.] Mt Sinai, Icahn Sch Med, Pediat, New York, NY USA.
RI Ueno, Hideki/L-1237-2016
OI Ueno, Hideki/0000-0001-7747-0738
NR 0
TC 0
Z9 0
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2014
VL 133
IS 2
SU S
MA 1005
BP AB292
EP AB292
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 297FO
UT WOS:000330241301320
ER
PT J
AU Glesner, J
Mueller, G
Pedersen, L
Chapman, MD
Pomes, A
AF Glesner, Jill
Mueller, Geoffrey
Pedersen, Lars
Chapman, Martin D.
Pomes, Anna
TI Antigenic Analysis Of The Major Cockroach Allergen Bla g 5 and Its Dust
Mite Homolog Der p 8
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 28-MAR 04, 2014
CL San Diego, CA
SP Amer Acad Allergy Asthma & Immunol
C1 [Glesner, Jill; Chapman, Martin D.; Pomes, Anna] Indoor Biotechnol Inc, Charlottesville, VA USA.
[Mueller, Geoffrey; Pedersen, Lars] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2014
VL 133
IS 2
SU S
MA 349
BP AB100
EP AB100
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 297FO
UT WOS:000330241300347
ER
PT J
AU Hox, V
Desai, A
Bandara, G
Gilfillan, AM
Beaven, M
Olivera, A
Metcalfe, DD
AF Hox, Valerie
Desai, Avanti
Bandara, Geethani
Gilfillan, Alasdair M.
Beaven, Michael
Olivera, Ana
Metcalfe, Dean D.
TI Estradiol Has a Negative Impact On The Anaphylactic Response In Mice,
Independent From Mast Cell Degranulation
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 28-MAR 04, 2014
CL San Diego, CA
SP Amer Acad Allergy Asthma & Immunol
C1 [Hox, Valerie; Desai, Avanti; Bandara, Geethani; Gilfillan, Alasdair M.; Olivera, Ana; Metcalfe, Dean D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
[Hox, Valerie] KULeuven, Clin Immunol Lab, Dept Microbiol & Immunol, Louvain, Belgium.
[Beaven, Michael] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2014
VL 133
IS 2
SU S
MA 208
BP AB58
EP AB58
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 297FO
UT WOS:000330241300206
ER
PT J
AU Jaffee, KF
Visness, C
O'Connor, GT
Bloomberg, GR
Kattan, M
Wood, RA
Gergen, PJ
Gern, JE
AF Jaffee, Katy F.
Visness, Cynthia
O'Connor, George T.
Bloomberg, Gordon R.
Kattan, Meyer
Wood, Robert A.
Gergen, Peter J.
Gern, James E.
TI Maternal Allergy and Asthma and Their Association With Breastfeeding In
Inner-City Mothers In a Birth Cohort Study (URECA)
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 28-MAR 04, 2014
CL San Diego, CA
SP Amer Acad Allergy Asthma & Immunol
C1 [Jaffee, Katy F.; Visness, Cynthia] Rho Inc, Chapel Hill, NC USA.
[O'Connor, George T.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Bloomberg, Gordon R.] St Louis Childrens Hosp, St Louis, MO 63178 USA.
[Kattan, Meyer] New York Presbyterian Columbia, New York, NY USA.
[Wood, Robert A.] Johns Hopkins Univ, Med Ctr, Baltimore, MD 21218 USA.
[Gergen, Peter J.] NIH, AAIB, DAIT, Bethesda, MD 20892 USA.
[Gern, James E.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2014
VL 133
IS 2
SU S
MA 55
BP AB15
EP AB15
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 297FO
UT WOS:000330241300054
ER
PT J
AU Khoury, P
Abiodun, A
Williams, K
Ware, J
Holland-Thomas, N
Klion, AD
AF Khoury, Paneez
Abiodun, Annalise
Williams, Kelli
Ware, JeanAnne
Holland-Thomas, Nicole
Klion, Amy D.
TI Predictors Of Response To Glucocorticoids In Hypereosinophilic Syndromes
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 28-MAR 04, 2014
CL San Diego, CA
SP Amer Acad Allergy Asthma & Immunol
C1 [Khoury, Paneez; Abiodun, Annalise; Williams, Kelli; Ware, JeanAnne; Klion, Amy D.] NIH, Bethesda, MD 20892 USA.
[Holland-Thomas, Nicole] SAIC Frederick Inc, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2014
VL 133
IS 2
SU S
MA 270
BP AB76
EP AB76
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 297FO
UT WOS:000330241300268
ER
PT J
AU Kirshenbaum, AS
Petrik, A
Walsh, R
Vepa, S
Metcalfe, DD
AF Kirshenbaum, Arnold S.
Petrik, Amy
Walsh, Rosemary
Vepa, Sury
Metcalfe, Dean D.
TI Worldwide Impact Of LAD2 Mast Cell Line On Mast Cell Biology Research
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 28-MAR 04, 2014
CL San Diego, CA
SP Amer Acad Allergy Asthma & Immunol
C1 [Kirshenbaum, Arnold S.; Metcalfe, Dean D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
[Petrik, Amy; Walsh, Rosemary] NIAID, Technol Transfer & Intellectual Property Off, NIH, Bethesda, MD 20892 USA.
[Vepa, Sury] NIH, Off Technol Transfer, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 5
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2014
VL 133
IS 2
SU S
MA 202
BP AB57
EP AB57
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 297FO
UT WOS:000330241300200
ER
PT J
AU Legrand, F
Tomasevic, N
Makiya, M
Bebbington, C
Klion, AD
AF Legrand, Fanny
Tomasevic, Nenad
Makiya, Michelle
Bebbington, Christopher
Klion, Amy D.
TI Human EMR1, An Eosinophil-Specific Surface Receptor Of Unknown Function,
Is Modulated In Vivo and In Vitro
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 28-MAR 04, 2014
CL San Diego, CA
SP Amer Acad Allergy Asthma & Immunol
C1 [Legrand, Fanny; Makiya, Michelle; Klion, Amy D.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2014
VL 133
IS 2
SU S
MA 216
BP AB61
EP AB61
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 297FO
UT WOS:000330241300214
ER
PT J
AU Lin, A
Sharma, HP
AF Lin, Adora
Sharma, Hemant P.
TI Teasing and Bullying Among Adolescents With Food Allergy
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 28-MAR 04, 2014
CL San Diego, CA
SP Amer Acad Allergy Asthma & Immunol
C1 [Lin, Adora] NIAID, Bethesda, MD 20892 USA.
[Sharma, Hemant P.] Childrens Natl Med Ctr, Div Allergy & Immunol, Washington, DC 20010 USA.
NR 0
TC 2
Z9 2
U1 1
U2 5
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2014
VL 133
IS 2
SU S
MA 995
BP AB288
EP AB288
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 297FO
UT WOS:000330241301310
ER
PT J
AU Lyons, JJ
Sun, GP
Stone, KD
Nelson, C
Wisch, L
O'Brien, M
Jones, N
Lindsley, AW
Komarow, HD
Bai, Y
Scott, LM
Cantave, D
Maric, I
Abonia, JP
Rothenberg, ME
Schwartz, LB
Wilson, TM
Milner, JD
AF Lyons, Jonathan J.
Sun, Guangping
Stone, Kelly D.
Nelson, Celeste
Wisch, Laura
O'Brien, Michelle
Jones, Nina
Lindsley, Andrew W.
Komarow, Hirsh D.
Bai, Yun
Scott, Linda M.
Cantave, Daly
Maric, Irina
Abonia, J. Pablo
Rothenberg, Marc E.
Schwartz, Lawrence B.
Wilson, Todd M.
Milner, Joshua D.
TI Mendelian Inheritance Of Elevated Tryptase Associated With Atopy and
Connective Tissue Abnormalities
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 28-MAR 04, 2014
CL San Diego, CA
SP Amer Acad Allergy Asthma & Immunol
C1 [Lyons, Jonathan J.; Sun, Guangping; Stone, Kelly D.; Nelson, Celeste; Wisch, Laura; O'Brien, Michelle; Komarow, Hirsh D.; Bai, Yun; Scott, Linda M.; Wilson, Todd M.; Milner, Joshua D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
[Jones, Nina] Frederick Natl Lab Clin Res, Frederick, MD USA.
[Lindsley, Andrew W.; Abonia, J. Pablo; Rothenberg, Marc E.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
[Cantave, Daly] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Maric, Irina] NIH, Dept Lab Med, Bethesda, MD 20892 USA.
[Schwartz, Lawrence B.] Virginia Commonwealth Univ, Richmond, VA USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2014
VL 133
IS 2
SU S
MA 573
BP AB165
EP AB165
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 297FO
UT WOS:000330241300570
ER
PT J
AU Metcalfe, DD
Arceo, S
Young, ML
Nelson, C
Komarow, HD
AF Metcalfe, Dean D.
Arceo, Sarah
Young, Michael L.
Nelson, Celeste
Komarow, Hirsh D.
TI Outcome Measures Of Challenge Testing In Patients With Physically
Induced-Urticaria
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 28-MAR 04, 2014
CL San Diego, CA
SP Amer Acad Allergy Asthma & Immunol
C1 [Metcalfe, Dean D.; Arceo, Sarah; Nelson, Celeste; Komarow, Hirsh D.] NIAID, NIH, Lab Allerg Dis, Bethesda, MD 20892 USA.
[Young, Michael L.] SAIC Frederick Inc, Clin Res Directorate CMRP, Frederick Natl Lab Clin Res, Frederick, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2014
VL 133
IS 2
SU S
MA 409
BP AB116
EP AB116
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 297FO
UT WOS:000330241300406
ER
PT J
AU Milner, JD
Lyons, JJ
Zhang, Y
Yu, XM
Datta, S
Lamborn, IT
Biancalana, MR
Wolfe, LA
DiMaggio, T
Matthews, HF
Kranick, SM
Stone, KD
Holland, SM
Reich, DS
Hughes, JD
Mehmet, H
McElwee, J
Freeze, HH
Freeman, AFF
Su, HC
AF Milner, Joshua D.
Lyons, Jonathan J.
Zhang, Yu
Yu, Xiaomin
Datta, Shrimati
Lamborn, Ian T.
Biancalana, Matthew R.
Wolfe, Lynne A.
DiMaggio, Thomas
Matthews, Helen F.
Kranick, Sarah M.
Stone, Kelly D.
Holland, Steven M.
Reich, Daniel S.
Hughes, Jason D.
Mehmet, Huseyin
McElwee, Joshua
Freeze, Hudson H.
Freeman, Alexandra F. F.
Su, Helen C.
TI Impaired Glycosylation Due To Autosomal Recessive PGM3 Mutations Results
In Atopy, Immune Deficiency, Autoimmunity, and Neurocognitive Impairment
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 28-MAR 04, 2014
CL San Diego, CA
SP Amer Acad Allergy Asthma & Immunol
C1 [Milner, Joshua D.; Lyons, Jonathan J.; Yu, Xiaomin; Datta, Shrimati; Stone, Kelly D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
[Zhang, Yu; Lamborn, Ian T.; DiMaggio, Thomas; Su, Helen C.] NIAID, Lab Host Def, NIH, Bethesda, MD 20892 USA.
[Biancalana, Matthew R.; Matthews, Helen F.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Wolfe, Lynne A.] NHGRI, Undiagnosed Dis Program, NHI, Bethesda, MD 20892 USA.
[Kranick, Sarah M.] NINDS, Med Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Holland, Steven M.; Freeman, Alexandra F. F.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Reich, Daniel S.] NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA.
[Hughes, Jason D.; Mehmet, Huseyin; McElwee, Joshua] Merck & Co Inc, Merck Res Labs, Boston, MA USA.
[Freeze, Hudson H.] Sanford Burnham Med Res Inst, La Jolla, CA USA.
RI Reich, Daniel/E-5701-2010; Su, Helen/H-9541-2015
OI Reich, Daniel/0000-0002-2628-4334; Su, Helen/0000-0002-5582-9110
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2014
VL 133
IS 2
SU S
MA 561
BP AB161
EP AB161
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 297FO
UT WOS:000330241300558
ER
PT J
AU Moran, TP
Nakano, H
Kondilis-Mangum, H
Wade, P
Cook, D
AF Moran, Timothy P.
Nakano, Hideki
Kondilis-Mangum, Hrisavgi
Wade, Paul
Cook, Donald
TI Epigenetic Regulation Of Dendritic Cell Migration
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 28-MAR 04, 2014
CL San Diego, CA
SP Amer Acad Allergy Asthma & Immunol
C1 [Moran, Timothy P.] Duke Univ, Med Ctr, Durham, NC USA.
[Nakano, Hideki; Kondilis-Mangum, Hrisavgi; Wade, Paul; Cook, Donald] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2014
VL 133
IS 2
SU S
MA 980
BP AB284
EP AB284
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 297FO
UT WOS:000330241301295
ER
PT J
AU Mueller, G
Ankney, J
Pedersen, L
Khurana, T
Slater, JE
Glesner, J
Pomes, A
London, R
AF Mueller, Geoffrey
Ankney, John
Pedersen, Lars
Khurana, Taruna
Slater, Jay E.
Glesner, Jill
Pomes, Anna
London, Robert
TI Epitope Mapping Of An Anti-Bla g 1 ScFv Used For Cockroach Allergen
Quantitation
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 28-MAR 04, 2014
CL San Diego, CA
SP Amer Acad Allergy Asthma & Immunol
C1 [Mueller, Geoffrey; Ankney, John; Pedersen, Lars; London, Robert] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
[Khurana, Taruna] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA.
[Slater, Jay E.] US FDA, CBER, OVRR, DBPAP, Rockville, MD 20857 USA.
[Glesner, Jill; Pomes, Anna] Indoor Biotechnol Inc, Charlottesville, VA USA.
NR 0
TC 0
Z9 0
U1 0
U2 4
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2014
VL 133
IS 2
SU S
MA 348
BP AB100
EP AB100
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 297FO
UT WOS:000330241300346
ER
PT J
AU Munoz-Cano, RM
Bartra, J
Scheffel, J
Pascal, M
Dema, B
Valero, A
Olivera, A
Picado, C
Rivera, J
AF Munoz-Cano, Rosa M.
Bartra, Joan
Scheffel, Jorg
Pascal, Mariona
Dema, Barbara
Valero, Antonio
Olivera, Ana
Picado, Cesar
Rivera, Juan
TI Gene Expression Profiling Of Food-Induced Anaphylaxis Associated With
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 28-MAR 04, 2014
CL San Diego, CA
SP Amer Acad Allergy Asthma & Immunol
C1 [Munoz-Cano, Rosa M.; Scheffel, Jorg; Dema, Barbara; Olivera, Ana; Rivera, Juan] Natl Inst Arthrit & Musculoskeletal & Skin Dis NI, NIH, Bethesda, MD USA.
[Munoz-Cano, Rosa M.; Bartra, Joan; Valero, Antonio; Picado, Cesar] Hosp Clin Barcelona, Unitat Allergia, Serv Neumol & Allergia Resp, Barcelona, Spain.
[Munoz-Cano, Rosa M.; Bartra, Joan; Valero, Antonio; Picado, Cesar] Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain.
[Pascal, Mariona] Hosp Clin Barcelona, Serv Immunol, Ctr Diagnost Biomed, Barcelona, Spain.
RI Munoz Cano, Rosa/K-9413-2014; Bartra, Joan/L-4550-2014
OI Munoz Cano, Rosa/0000-0001-8566-8285; Bartra, Joan/0000-0001-7767-4730
NR 0
TC 0
Z9 0
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2014
VL 133
IS 2
SU S
MA 105
BP AB29
EP AB29
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 297FO
UT WOS:000330241300104
ER
PT J
AU Pazdrak, K
Khoury, P
Soman, KV
Holland-Thomas, N
Makiya, M
Straub, C
Wu, Z
Klion, AD
Kurosky, A
AF Pazdrak, Konrad
Khoury, Paneez
Soman, Kizhake V.
Holland-Thomas, Nicole
Makiya, Michelle
Straub, Christof
Wu, Zheng
Klion, Amy D.
Kurosky, Alexander
TI Differential Proteomic Analysis Of Eosinophils From Patients With
Glucocorticoid Responsive Or Resistant Hypereosinophilic Syndrome
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 28-MAR 04, 2014
CL San Diego, CA
SP Amer Acad Allergy Asthma & Immunol
C1 [Pazdrak, Konrad; Soman, Kizhake V.; Straub, Christof; Wu, Zheng; Kurosky, Alexander] Univ Texas Med Branch, Galveston, TX 77555 USA.
[Khoury, Paneez; Makiya, Michelle; Klion, Amy D.] NIH, Bethesda, MD 20892 USA.
[Holland-Thomas, Nicole] SAIC Frederick Inc, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2014
VL 133
IS 2
SU S
MA 271
BP AB77
EP AB77
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 297FO
UT WOS:000330241300269
ER
PT J
AU Williams, K
Ware, J
Abiodun, A
Khoury, P
Klion, AD
AF Williams, Kelli
Ware, JeanAnne
Abiodun, Annalise
Khoury, Paneez
Klion, Amy D.
TI Hypereosinophilia In Children and Adults: A Retrospective Comparison
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 28-MAR 04, 2014
CL San Diego, CA
SP Amer Acad Allergy Asthma & Immunol
C1 [Williams, Kelli; Ware, JeanAnne; Abiodun, Annalise; Khoury, Paneez; Klion, Amy D.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2014
VL 133
IS 2
SU S
MA 523
BP AB149
EP AB149
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 297FO
UT WOS:000330241300520
ER
PT J
AU Wood, RA
McGowan, EC
Bloomberg, GR
Gergen, PJ
Visness, C
Jaffee, K
O'Connor, GT
Kattan, M
Gern, JE
AF Wood, Robert A.
McGowan, Emily C.
Bloomberg, Gordon R.
Gergen, Peter J.
Visness, Cynthia
Jaffee, Katy
O'Connor, George T.
Kattan, Meyer
Gern, James E.
TI The Prevalence Of Food Sensitization and Food Allergy In An Inner City
Birth Cohort
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 28-MAR 04, 2014
CL San Diego, CA
SP Amer Acad Allergy Asthma & Immunol
C1 [Wood, Robert A.] Johns Hopkins Univ, Med Ctr, Baltimore, MD 21218 USA.
[McGowan, Emily C.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Bloomberg, Gordon R.] St Louis Childrens Hosp, St Louis, MO 63178 USA.
[Gergen, Peter J.] NIH, AAIB, DAIT, Bethesda, MD 20892 USA.
[Visness, Cynthia] Rho Fed Syst Div Inc, Chapel Hill, NC USA.
[Jaffee, Katy] Rho Inc, Chapel Hill, NC USA.
[O'Connor, George T.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Kattan, Meyer] NewYork Presbyterian Columbia, New York, NY USA.
[Gern, James E.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2014
VL 133
IS 2
SU S
MA 694
BP AB200
EP AB200
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 297FO
UT WOS:000330241301010
ER
PT J
AU Zabel, RA
Gergen, PJ
Sorkness, CA
Wildfire, J
Calatroni, A
Mitchell, H
AF Zabel, Rebecca A.
Gergen, Peter J.
Sorkness, Christine A.
Wildfire, Jeremy
Calatroni, Agustin
Mitchell, Herman
TI Determining Risk Levels Of The Composite Asthma Severity Index (CASI)
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 28-MAR 04, 2014
CL San Diego, CA
SP Amer Acad Allergy Asthma & Immunol
C1 [Zabel, Rebecca A.; Wildfire, Jeremy; Calatroni, Agustin; Mitchell, Herman] Rho Inc, Chapel Hill, NC USA.
[Gergen, Peter J.] AAIB DAIT NIH, Bethesda, MD USA.
[Sorkness, Christine A.] Univ Wisconsin, Madison, WI USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2014
VL 133
IS 2
SU S
MA 976
BP AB283
EP AB283
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 297FO
UT WOS:000330241301291
ER
PT J
AU Liu, ZP
Wang, JJ
Huang, EW
Gao, S
Li, H
Lu, J
Tian, KM
Little, PJ
Shen, XY
Xu, SW
Liu, PQ
AF Liu, Zhiping
Wang, Jiaojiao
Huang, Erwen
Gao, Si
Li, Hong
Lu, Jing
Tian, Kunming
Little, Peter J.
Shen, Xiaoyan
Xu, Suowen
Liu, Peiqing
TI Tanshinone IIA suppresses cholesterol accumulation in human macrophages:
role of heme oxygenase-1
SO JOURNAL OF LIPID RESEARCH
LA English
DT Article
DE class A scavenger receptor; ATP-binding cassette transporter A1/G1; heme
catabolism enzyme; cell signaling
ID ANTIOXIDANT RESPONSE ELEMENT; CASSETTE TRANSPORTER A1; KAPPA-B
ACTIVATION; SCAVENGER RECEPTORS; OXIDATIVE STRESS; TARGETED DISRUPTION;
GENE-EXPRESSION; OXIDIZED LDL; FOAM CELLS; ATHEROSCLEROSIS
AB Accumulation of foam cells in the neointima represents a key event in atherosclerosis. We previously demonstrated that Tanshinone IIA (Tan), a lipophilic bioactive compound extracted from Salvia miltiorrhiza Bunge, inhibits experimental atherogenesis, yet the detailed mechanisms are not fully understood. In this study, we sought to explore the potential effects of Tan on lipid accumulation in macrophage foam cells and the underlying molecular mechanisms. Our data indicate that Tan treatment reduced the content of macrophages, cholesterol accumulation, and the development of atherosclerotic plaque in apolipoprotein E-deficient mice. In human macrophages, Tan ameliorated oxidized low density lipoporotein (oxLDL)-elicited foam cell formation by inhibiting oxLDL uptake and promoting cholesterol efflux. Mechanistically, Tan markedly reduced the expression of scavenger receptor class A and increased the expression of ATP-binding cassette transporter A1 (ABCA1) and ABCG1 in lipid-laden macrophages via activation of the extracellular signal-regulated kinase (ERK)/nuclear factor-erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. Tan treatment induced the phosphorylation and nuclear translocation of Nrf2 and subsequently increased the expression of HO-1, and these effects were abolished by the specific ERK inhibitors, PD98059 and U0126. Moreover, HO-1 small interfering RNA or zinc protoporphyrin (a HO-1 inhibitor) abrogated Tan-mediated suppression of lipid accumulation in macrophages. Our current findings demonstrate that a novel HO-1-dependent mechanism is involved in the regulation of cholesterol balance by Tan.
C1 [Liu, Zhiping; Wang, Jiaojiao; Gao, Si; Li, Hong; Lu, Jing; Shen, Xiaoyan; Xu, Suowen; Liu, Peiqing] Sun Yat Sen Univ, Sch Pharmaceut Sci, Dept Pharmacol & Toxicol, Guangzhou 510006, Guangdong, Peoples R China.
[Huang, Erwen] Guangzhou Forens Sci Inst, Guangzhou 510030, Guangdong, Peoples R China.
[Huang, Erwen] Sun Yat Sen Univ, Zhongshan Sch Med, Dept Forens Pathol, Guangzhou 510080, Guangdong, Peoples R China.
[Tian, Kunming] Guangdong Pharmaceut Univ, Sch Publ Hlth, Guangzhou 510310, Peoples R China.
[Little, Peter J.] RMIT Univ, Hlth Innovat Res Inst, Sch Med Sci & Diabet Complicat Grp, Discipline Pharm, Bundoora, Vic 3083, Australia.
[Xu, Suowen] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA.
RP Xu, SW (reprint author), Sun Yat Sen Univ, Sch Pharmaceut Sci, Dept Pharmacol & Toxicol, Guangzhou 510006, Guangdong, Peoples R China.
EM suo-wen.xu@nih.gov; liupq@mail.sysu.edu.cn
RI Little, Peter/F-9865-2015
OI Little, Peter/0000-0002-0335-3835
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
Natural Science Foundation of Guangdong Province [S2011030003190]; Major
Project of Guangdong Province [2008A030201013, 2012A080201007]
FX This work was supported by research grants from the National Natural
Science Foundation of China (81072641, 81273499), the National Science
and Technology Major Project of China "Key New Drug Creation and
Manufacturing Program" (2011ZX09401-307), Team Item of Natural Science
Foundation of Guangdong Province (S2011030003190), and Major Project of
Guangdong Province (2008A030201013, 2012A080201007). The authors have no
conflicts of interest to disclose.
NR 51
TC 15
Z9 24
U1 0
U2 35
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 FEB
PY 2014
VL 55
IS 2
BP 201
EP 213
DI 10.1194/jlr.M040394
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 301MG
UT WOS:000330535800005
PM 24302760
ER
PT J
AU Morens, DM
Taubenberger, JK
AF Morens, David M.
Taubenberger, Jeffery K.
TI A possible outbreak of swine influenza, 1892
SO LANCET INFECTIOUS DISEASES
LA English
DT Editorial Material
ID VIRUS; EPIDEMIC; ANTIBODY
AB Influenza A viruses are globally enzootic in swine populations. Swine influenza has been recognised only since 1918, but an anecdotal report suggests that a swine-influenza epizootic might have occurred in England in 1892, at the same time as an explosive epidemic (or pandemic recurrence) of human influenza. This outbreak suggests that the ecobiological association between human and swine influenza could extend to before 1918. By contrast with the recent documentation of swine influenza, influenza in horses has been well documented for hundreds of years, and was often linked temporally and geographically to epidemics of human influenza. Both decreased contact between people and horses, and the concomitant increase in swine production over the past century, might have altered the character and dynamics of influenza host-switch events between people and domestic mammals.
C1 [Morens, David M.] NIAID, Off Director, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Taubenberger, Jeffery K.] NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Morens, DM (reprint author), NIAID, Off Director, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM dmorens@niaid.nih.gov
FU Intramural NIH HHS [ZIA AI000995-07]
NR 27
TC 4
Z9 4
U1 1
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1473-3099
EI 1474-4457
J9 LANCET INFECT DIS
JI Lancet Infect. Dis.
PD FEB
PY 2014
VL 14
IS 2
BP 169
EP 172
DI 10.1016/S1473-3099(13)70227-5
PG 4
WC Infectious Diseases
SC Infectious Diseases
GA 299UE
UT WOS:000330420400030
PM 24290840
ER
PT J
AU Song, R
Bi, GH
Zhang, HY
Yang, RF
Gardner, EL
Li, J
Xi, ZX
AF Song, Rui
Bi, Guo-Hua
Zhang, Hai-Ying
Yang, Ri-Fang
Gardner, Eliot L.
Li, Jin
Xi, Zheng-Xiong
TI Blockade of D3 receptors by YQA14 inhibits cocaine's rewarding effects
and relapse to drug-seeking behavior in rats
SO NEUROPHARMACOLOGY
LA English
DT Article
DE Cocaine; Dopamine; D3 receptors; YQA14; Reward; Reinstatement
ID DOPAMINE D-3 RECEPTOR; BRAIN-STIMULATION REWARD; NUCLEUS-ACCUMBENS;
PHARMACOLOGICAL ACTIONS; ANIMAL-MODELS; HIGH-AFFINITY; ANTAGONIST;
ADDICTION; EXTINCTION; NEUROBIOLOGY
AB Preclinical studies suggest that dopamine D3 receptor (D3R) antagonists are promising for the treatment of drug abuse and addiction. However, few D3R antagonists have potential to be tested in humans due to short half-life, toxicity or limited preclinical research into pharmacotherapeutic efficacy. Here, we report on a novel D3R antagonist YQA14, which has improved half-life and pharmacokinetic profile and which displays potent pharmacotherapeutic efficacy in attenuating cocaine reward and relapse to drug-seeking behavior. Electrical brain-stimulation reward (BSR) in laboratory animals is a highly sensitive experimental approach to evaluate a drug's rewarding effects. We found that cocaine (2 mg/kg) significantly enhanced electrical BSR in rats (i.e., decreased stimulation threshold for BSR), while YQA14 alone had no effect on BSR. Pretreatment with YQA14 significantly and dose-dependently attenuated cocaine-enhanced BSR. YQA14 also facilitated extinction from drug-seeking behavior in rats during early behavioral extinction, and attenuated cocaine- or contextual cue-induced relapse to drug-seeking behavior. YQA14 alone did not maintain self-administration in either naive rats or in rats experienced at cocaine self-administration. YQA14 also inhibited expression of repeated cocaine-induced behavioral sensitization. These findings suggest that YQA14 may have pharmacotherapeutic potential in attenuating cocaine-taking and cocaine-seeking behavior. Thus, YQA14 deserves further investigation as a promising agent for treatment of cocaine addiction. Published by Elsevier Ltd.
C1 [Song, Rui; Bi, Guo-Hua; Zhang, Hai-Ying; Gardner, Eliot L.; Xi, Zheng-Xiong] NIDA, Intramural Res Program, Baltimore, MD 21224 USA.
[Song, Rui; Yang, Ri-Fang; Li, Jin] Beijing Inst Pharmacol & Toxicol, Beijing 100850, Peoples R China.
RP Xi, ZX (reprint author), NIDA, Intramural Res Program, Baltimore, MD 21224 USA.
EM jinli9802@163.com; zxi@intra.nida.nih.gov
OI Zhang, Haiying/0000-0003-0593-5940; Yang, Rifang/0000-0001-8087-9614
FU U.S. National Institute on Drug Abuse Intramural Research Program;
National Basic Research Program of China [2009CB522008]; Natural Science
Foundation of China [81102425]
FX This work was supported by the U.S. National Institute on Drug Abuse
Intramural Research Program, the National Basic Research Program of
China (No. 2009CB522008) and the Natural Science Foundation of China
(Grant No. 81102425).
NR 53
TC 13
Z9 13
U1 0
U2 9
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3908
EI 1873-7064
J9 NEUROPHARMACOLOGY
JI Neuropharmacology
PD FEB
PY 2014
VL 77
BP 398
EP 405
DI 10.1016/j.neuropharm.2013.10.010
PG 8
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 300UR
UT WOS:000330490000041
PM 24176392
ER
PT J
AU Devkota, KP
Wilson, JA
Henrich, CJ
McMahon, JB
Reilly, KM
Beutler, JA
AF Devkota, Krishna P.
Wilson, Jennifer A.
Henrich, Curtis J.
McMahon, James B.
Reilly, Karlyne M.
Beutler, John A.
TI Compounds from Simarouba berteroana which inhibit proliferation of
NF1-defective cancer cells
SO PHYTOCHEMISTRY LETTERS
LA English
DT Article
DE Simarouba berteroana; Neurofibromatosis type 1; Canthine alkaloids;
Growth inhibition; Glioblastomas
ID BETA-CARBOLINE ALKALOIDS; CANTHIN-6-ONE ALKALOIDS; EURYCOMA-LONGIFOLIA;
MEDICINAL-PLANTS; CONSTITUENTS; NEUROFIBROMATOSIS; ROOTS
AB A neurofibromatosis type 1 (NF1) based bioassay-guided phytochemical investigation on Simarouba berteroana led to the isolation of one new canthin-6-one-9-methoxy-5-O-beta-D-glucopyranoside (1), seven known canthine alkaloids (2-8), two known quassinoids (9-10) and a known neo-lignan (11). The structures of all compounds were established by HRMS, 1D- and 2D NMR analysis and comparison with previously reported data. Most of the compounds inhibited the proliferation of an Nf1- and p53-deficient mouse glioma cell line at non-cytotoxic concentrations. Published by Elsevier Ireland Ltd on behalf of Phytochemical Society of Europe.
C1 [Devkota, Krishna P.; Wilson, Jennifer A.; Henrich, Curtis J.; McMahon, James B.; Beutler, John A.] Ctr Canc Res, Mol Targets Lab, Frederick, MD 21702 USA.
[Henrich, Curtis J.] SAIC Frederick, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Reilly, Karlyne M.] Ctr Canc Res, Mouse Canc Genet Program, Frederick, MD 21702 USA.
RP Beutler, JA (reprint author), Ctr Canc Res, Mol Targets Lab, Frederick, MD 21702 USA.
EM krishna.devkota@nih.gov; wilsonje@mail.nih.gov; henrichcj@mail.nih.gov;
mcmahoja@mail.nih.gov; reillyk@mail.nih.gov; beutlerj@mail.nih.gov
FU Frederick National Laboratory for Cancer Research, National Institutes
of Health [HHSN261200800001E]
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research. This project
has been funded in whole or in part with Federal funds from the
Frederick National Laboratory for Cancer Research, National Institutes
of Health, under contract HHSN261200800001E. The content of this
publication does not necessarily reflect the views or policies of the
Department of Health and Human Services, nor does mention of trade
names, commercial products or organizations imply endorsement by the US
Government. We thank D. Garcia and J. Pimentel for the plant collection,
and David Newman, Deborah Bell and James Miller for help in documenting
the collection, as well as the Natural Products Support Group at
NCI-Frederick for extraction, and Sergey Tarasov and Marzena Dyba
(Biophysics Resource Core, Structural Biophysics Laboratory, CCR) for
assistance with mass spectrometry.
NR 22
TC 5
Z9 5
U1 0
U2 12
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1874-3900
EI 1876-7486
J9 PHYTOCHEM LETT
JI Phytochem. Lett.
PD FEB
PY 2014
VL 7
BP 42
EP 45
DI 10.1016/j.phytol.2013.09.007
PG 4
WC Plant Sciences; Oncology
SC Plant Sciences; Oncology
GA 302CE
UT WOS:000330578100010
PM 24443661
ER
PT J
AU Romero, R
Yeo, L
Chaemsaithong, P
Chaiworapongsa, T
Hassan, SS
AF Romero, Roberto
Yeo, Lami
Chaemsaithong, Piya
Chaiworapongsa, Tinnakorn
Hassan, Sonia S.
TI Progesterone to prevent spontaneous preterm birth
SO SEMINARS IN FETAL & NEONATAL MEDICINE
LA English
DT Article
DE Cervical cerclage; Cervical length; Cervical ultrasound; Short cervix;
Ultrasound; Vaginal progesterone
ID PLACEBO-CONTROLLED TRIAL; ULTRASONOGRAPHIC CERVICAL LENGTH; WHITE-MATTER
LESIONS; VAGINAL PROGESTERONE; DOUBLE-BLIND;
17-ALPHA-HYDROXYPROGESTERONE CAPROATE; INTRAAMNIOTIC INFLAMMATION;
TRANSVAGINAL ULTRASOUND; SONOGRAPHIC MEASUREMENT; PREGNANCY MAINTENANCE
AB Preterm birth is the leading cause of perinatal morbidity and mortality worldwide, and its prevention is an important healthcare priority. Preterm parturition is one of the 'great obstetrical syndromes' and is caused by multiple etiologies. One of the mechanisms of disease is the untimely decline in progesterone action, which can present as a clinically silent sonographic short cervix in the midtrimester. The detection of a short cervix in the midtrimester is a powerful risk factor for preterm delivery. Vaginal progesterone can reduce the rate of preterm delivery by 45% and the rate of neonatal morbidity (admission to the neonatal intensive care unit, respiratory distress syndrome, need for mechanical ventilation, etc.). To prevent one case of spontaneous preterm birth <33 weeks of gestation, 11 patients with a short cervix would need to be treated (based on an individual patient meta-analysis). Vaginal progesterone reduces the rate of spontaneous preterm birth in women with a short cervix, both with and without a prior history of preterm birth. In patients with a prior history of preterm birth, vaginal progesterone is as effective as cervical cerclage to prevent preterm delivery. 17 alpha-Hydroxyprogesterone caproate has not been shown to be effective in reducing the rate of spontaneous preterm birth in women with a short cervix. Published by Elsevier Ltd.
C1 [Romero, Roberto; Yeo, Lami; Chaemsaithong, Piya; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,NIH, Detroit, MI USA.
[Romero, Roberto] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA.
[Romero, Roberto] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA.
[Yeo, Lami; Chaemsaithong, Piya; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA.
RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD,NIH,DHHS, 3990 John R,Box 4, Detroit, MI 48201 USA.
EM romeror@mail.nih.gov
FU Perinatology Research Branch; Division of Intramural Research; Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health; Department of Health and
Human Services (NICHD/NIH); NICHD, NIH [HHSN275201300006C]
FX This work was supported, in part, by the Perinatology Research Branch,
Division of Intramural Research, Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health, Department of Health and Human Services (NICHD/NIH); and, in
part, with Federal funds from NICHD, NIH under Contract No.
HHSN275201300006C.
NR 129
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U1 0
U2 13
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1744-165X
EI 1878-0946
J9 SEMIN FETAL NEONAT M
JI Semin. Fetal Neonatal Med.
PD FEB
PY 2014
VL 19
IS 1
BP 15
EP 26
DI 10.1016/j.siny.2013.10.004
PG 12
WC Pediatrics
SC Pediatrics
GA 300WY
UT WOS:000330495900004
PM 24315687
ER
PT J
AU Vlaanderen, J
Portengen, L
Schuz, J
Olsson, A
Pesch, B
Kendzia, B
Stucker, I
Guida, F
Bruske, I
Wichmann, HE
Consonni, D
Landi, MT
Caporaso, N
Siemiatycki, J
Merletti, F
Mirabelli, D
Richiardi, L
Gustavsson, P
Plato, N
Jockel, KH
Ahrens, W
Pohlabeln, H
Tardon, A
Zaridze, D
Field, JK
Mannetje, A'T
Pearce, N
McLaughlin, J
Demers, P
Szeszenia-Dabrowska, N
Lissowska, J
Rudnai, P
Fabianova, E
Dumitru, RS
Bencko, V
Foretova, L
Janout, V
Boffetta, P
Forastiere, F
Bueno-De-Mesquita, B
Peters, S
Bruning, T
Kromhout, H
Straif, K
Vermeulen, R
AF Vlaanderen, Jelle
Portengen, Lutzen
Schuez, Joachim
Olsson, Ann
Pesch, Beate
Kendzia, Benjamin
Stuecker, Isabelle
Guida, Florence
Brueske, Irene
Wichmann, Heinz-Erich
Consonni, Dario
Landi, Maria Teresa
Caporaso, Neil
Siemiatycki, Jack
Merletti, Franco
Mirabelli, Dario
Richiardi, Lorenzo
Gustavsson, Per
Plato, Nils
Joeckel, Karl-Heinz
Ahrens, Wolfgang
Pohlabeln, Hermann
Tardon, Adonina
Zaridze, David
Field, John K.
Mannetje, Andrea ' t
Pearce, Neil
McLaughlin, John
Demers, Paul
Szeszenia-Dabrowska, Neonila
Lissowska, Jolanta
Rudnai, Peter
Fabianova, Eleonora
Dumitru, Rodica Stanescu
Bencko, Vladimir
Foretova, Lenka
Janout, Vladimir
Boffetta, Paolo
Forastiere, Francesco
Bueno-de-Mesquita, Bas
Peters, Susan
Bruening, Thomas
Kromhout, Hans
Straif, Kurt
Vermeulen, Roel
TI Effect Modification of the Association of Cumulative Exposure and Cancer
Risk by Intensity of Exposure and Time Since Exposure Cessation: A
Flexible Method Applied to Cigarette Smoking and Lung Cancer in the
SYNERGY Study
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE cigarette smoke; cumulative exposure; effect modification; lung cancer;
pooled analysis
ID MODELING TOTAL EXPOSURE; OCCUPATIONAL-EXPOSURE; POOLED ANALYSIS; EUROPE;
CARCINOMA; ALCOHOL; SMOKERS
AB The indiscriminate use of the cumulative exposure metric (the product of intensity and duration of exposure) might bias reported associations between exposure to hazardous agents and cancer risk. To assess the independent effects of duration and intensity of exposure on cancer risk, we explored effect modification of the association of cumulative exposure and cancer risk by intensity of exposure. We applied a flexible excess odds ratio model that is linear in cumulative exposure but potentially nonlinear in intensity of exposure to 15 case-control studies of cigarette smoking and lung cancer (19852009). Our model accommodated modification of the excess odds ratio per pack-year of cigarette smoking by time since smoking cessation among former smokers. We observed negative effect modification of the association of pack-years of cigarette smoking and lung cancer by intensity of cigarette smoke for persons who smoked more than 2030 cigarettes per day. Patterns of effect modification were similar across individual studies and across major lung cancer subtypes. We observed strong negative effect modification by time since smoking cessation. Application of our method in this example of cigarette smoking and lung cancer demonstrated that reducing a complex exposure history to a metric such as cumulative exposure is too restrictive.
C1 [Vlaanderen, Jelle; Schuez, Joachim; Olsson, Ann; Straif, Kurt] Int Agcy Res Canc, F-69372 Lyon, France.
[Vlaanderen, Jelle; Portengen, Lutzen; Kromhout, Hans; Vermeulen, Roel] Inst Risk Assessment Sci, Utrecht, Netherlands.
[Olsson, Ann; Gustavsson, Per; Plato, Nils] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden.
[Pesch, Beate; Kendzia, Benjamin; Bruening, Thomas] Ruhr Univ Bochum, German Social Accid Insurance Inst, Inst Prevent & Occupat Med, Bochum, Germany.
[Stuecker, Isabelle; Guida, Florence] Ctr Res Epidemiol & Populat Hlth CESP, INSERM, Environm Epidemiol Canc Team, U1018, Villejuif, France.
[Stuecker, Isabelle; Guida, Florence] Univ Paris Sud, UMRS 1018, Villejuif, France.
[Brueske, Irene; Wichmann, Heinz-Erich] Deutsch Forschungszentrum Gesundheit & Umwelt, Inst Epidemiol 1, Neuherberg, Germany.
[Consonni, Dario] Osped Maggiore Policlin, Fdn Ist Ricovero & Cura Carattere Sci IRCCS CaGra, Epidemiol Unit, Milan, Italy.
[Landi, Maria Teresa; Caporaso, Neil] Natl Canc Inst, Bethesda, MD USA.
[Siemiatycki, Jack] Univ Montreal, Hosp Res Ctr, Montreal, PQ, Canada.
[Merletti, Franco; Mirabelli, Dario; Richiardi, Lorenzo] Univ Turin, Dept Med Sci, Canc Epidemiol Unit, Turin, Italy.
[Joeckel, Karl-Heinz] Univ Duisburg Essen, Inst Med Informat Biometry & Epidemiol, Essen, Germany.
[Ahrens, Wolfgang; Pohlabeln, Hermann] Bremen Inst Prevent Res & Social Med, Bremen, Germany.
[Tardon, Adonina] Univ Oviedo, Biomed Res Ctr Network Epidemiol & Publ Hlth CIBE, Oviedo, Spain.
[Zaridze, David] Russian Canc Res Ctr, Moscow, Russia.
[Field, John K.] Univ Liverpool, Canc Res Ctr, Dept Mol & Clin Canc Med, Roy Castle Lung Canc Res Programme, Liverpool L69 3BX, Merseyside, England.
[Mannetje, Andrea ' t; Pearce, Neil] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand.
[McLaughlin, John; Demers, Paul] Occupat Canc Res Ctr, Toronto, ON, Canada.
[Szeszenia-Dabrowska, Neonila] Nofer Inst Occupat Med, Lodz, Poland.
[Lissowska, Jolanta] M Sklodowska Curie Canc Ctr, Warsaw, Poland.
[Lissowska, Jolanta] Inst Oncol, Warsaw, Poland.
[Rudnai, Peter] Natl Inst Environm Hlth, Budapest, Hungary.
[Fabianova, Eleonora] Reg Author Publ Hlth, Banska Bystrica, Slovakia.
[Dumitru, Rodica Stanescu] Inst Publ Hlth, Bucharest, Romania.
[Bencko, Vladimir] Charles Univ Prague, Fac Med 1, Inst Hyg & Epidemiol, Prague, Czech Republic.
[Foretova, Lenka] Masaryk Mem Canc Inst, Brno, Czech Republic.
[Janout, Vladimir] Palacky Univ, Fac Med, CR-77147 Olomouc, Czech Republic.
[Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA.
[Boffetta, Paolo] Int Prevent Res Inst, Lyon, France.
[Forastiere, Francesco] ASL RomaE, Dept Epidemiol, Rome, Italy.
[Bueno-de-Mesquita, Bas] Natl Inst Publ Hlth & Environm Protect RIVM, Bilthoven, Netherlands.
[Peters, Susan] Western Australia Inst Med Res, Perth, WA, Australia.
RP Vlaanderen, J (reprint author), Univ Utrecht, Inst Risk Assessment Sci, POB 80178, NL-3508 TD Utrecht, Netherlands.
EM j.j.vlaanderen@uu.nl
RI Janout, Vladimir/M-5133-2014; Szeszenia-Dabrowska, Neonila/F-7190-2010;
Bruning, Thomas/G-8120-2015; Forastiere, Francesco/J-9067-2016;
Consonni, Dario/K-7943-2016; Vermeulen, Roel/F-8037-2011;
OI richiardi, lorenzo/0000-0003-0316-9402; Bruning,
Thomas/0000-0001-9560-5464; Forastiere, Francesco/0000-0002-9162-5684;
Consonni, Dario/0000-0002-8935-3843; Ahrens,
Wolfgang/0000-0003-3777-570X; Vermeulen, Roel/0000-0003-4082-8163;
Peters, Susan/0000-0001-5662-1971; Pearce, Neil/0000-0002-9938-7852;
Field, John/0000-0003-3951-6365
FU French Agency of Health Security; Fondation de France; French National
Research Agency, the National Institute of Cancer; Fondation for Medical
Research; The French Institute for Public Health Surveillance; Health
Ministry, the Organization for the Research on Cancer; French Ministry
of Work, Solidarity and Public Function; Organization for the Research
on Cancer; Federal Ministry of Education, Science, Research, and
Technology [01HK 173/0]; Federal Ministry of Science [01 HK 546/8];
Ministry of Labour and Social Affairs [IIIb7-27/13]; The International
Agency for Research on Cancer Multicenter Case-Control Study of
Occupational, Environment and Lung Cancer in Central and Eastern Europe
(INCO-COPERNICUS); European Commission's INCO-COPERNICUS program
[IC15-CT96-0313]; Polish State Committee for Scientific Research
[SPUB-M-COPERNICUS/P-05/DZ-30/99/2000]; Roy Castle Foundation; Italian
Association for Cancer Research, Region Piedmont; Compagnia di San
Paolo; Fondo de Investigacion Sanitaria; Ciber de Epidemiologia y Salud
Publica, Spain; Health Research Council of New Zealand; New Zealand
Department of Labour, Lottery Health Research; Cancer Society of New
Zealand; International Agency for Research on Cancer; European
commission
FX The SYNERGY project is funded by the German Social Accident Insurance.
The case-control study of environmental causes of lung cancer in
Montreal was supported by the Canadian Institutes for Health Research
and Guzzo-SRC Chair in Environment and Cancer. The Toronto study was
funded by the National Cancer Institute of Canada, with funds provided
by the Canadian Cancer Society, and the occupational analysis was
conducted by the Occupational Cancer Research Centre, which was
supported by the Workplace Safety and Insurance Board, the Canadian
Cancer Society, and Cancer Care Ontario. The Investigations Cancers
Respiratoires et Environnement study was supported by the French Agency
of Health Security, the Fondation de France, the French National
Research Agency, the National Institute of Cancer, the Fondation for
Medical Research, The French Institute for Public Health Surveillance,
The Health Ministry, the Organization for the Research on Cancer, and
the French Ministry of Work, Solidarity and Public Function. The lung
cancer study in France was supported by the Fondation de France. The
Paris lung cancer study was funded by Organization for the Research on
Cancer. The Arbeit und Technik Study in Germany was funded by Federal
Ministry of Education, Science, Research, and Technology grant 01 HK
173/0. The Humanisierung des Arbeitslebens Study was funded by the
Federal Ministry of Science (grant 01 HK 546/8) and the Ministry of
Labour and Social Affairs (grant IIIb7-27/13). The International Agency
for Research on Cancer Multicenter Case-Control Study of Occupational,
Environment and Lung Cancer in Central and Eastern Europe (
INCO-COPERNICUS) was supported by a grant from the European Commission's
INCO-COPERNICUS program (contract IC15-CT96-0313). In Warsaw, the study
was supported by grant SPUB-M-COPERNICUS/P-05/DZ-30/99/2000 from the
Polish State Committee for Scientific Research. In Liverpool, the work
was funded by the Roy Castle Foundation as part of the Liverpool Lung
Project. The Environment and Genetics in Lung Cancer Etiology Study was
funded by the Intramural Research Program of the National Institutes of
Health, National Cancer Institute, Division of Cancer Epidemiology and
Genetics, Bethesda, Maryland; Region, Italy; and the Istituto Nazionale
per l'Assicurazione contro gli Infortuni sul Lavoro, Rome, Italy. The
population-based case-control study of lung cancer in the city of Turin
was supported by the Italian Association for Cancer Research, Region
Piedmont, Compagnia di San Paolo. The study in Rome was conducted with a
partial support from the European Union Nuclear Fission Safety Program
(grant F14P-CT96-0055) and the Lazio Region. The Monitoring van
Risicofactoren en Gezondheid in Nederland Study was supported by the
Dutch Ministry of Health, Welfare & Sports, National Institute of Public
Health & the Environment, and the Europe Against Cancer Program. The
Cancer de Pulmon en Asturias Study was supported by the Instituto
Universitario de Oncologia, Universidad de Oviedo, Asturias, the Fondo
de Investigacion Sanitaria, and the Ciber de Epidemiologia y Salud
Publica, Spain. The Lungcancer I Stockholm Study was supported by the
Swedish Council forWork Life Research and the Swedish Environmental
Protection Agency. The Occupational Cancer in New Zealand Study was
funded by the Health Research Council of New Zealand, the New Zealand
Department of Labour, Lottery Health Research, and the Cancer Society of
New Zealand.; Part of the work reported in this articlewas undertaken
during the tenure of a Postdoctoral Fellowship from the International
Agency for Research on Cancer, partially supported by the European
commission FP7 Marie Curie Actions - People - Cofunding of regional,
national, and international programmes (COFUND).
NR 30
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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 FEB 1
PY 2014
VL 179
IS 3
BP 290
EP 298
DI 10.1093/aje/kwt273
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 296NA
UT WOS:000330190600003
PM 24355332
ER
PT J
AU Hernan, MA
Schisterman, EF
Hernandez-Diaz, S
AF Hernan, Miguel A.
Schisterman, Enrique F.
Hernandez-Diaz, Sonia
TI Invited Commentary: Composite Outcomes as an Attempt to Escape From
Selection Bias and Related Paradoxes
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Editorial Material
DE causal diagrams; composite outcomes; paradox; selection bias
ID BIRTH-WEIGHT PARADOX; MORTALITY; CURVES
AB This commentary reviews the recent history of explanations to crossover paradoxes such as the birth weight and gestational age paradoxes, with a special emphasis on the current proposal by Kramer et al. in this issue of the Journal (Am J Epidemiol. 2014;179(3):361367). We contend that the causal structure of these paradoxes is essentially identical to that of several well-known selection biases. We then consider the pros and cons of using composite outcomes to circumvent these selection biases.
C1 [Hernan, Miguel A.; Hernandez-Diaz, Sonia] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Hernan, Miguel A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Hernan, Miguel A.] Harvard Mit Div Hlth Sci & Technol, Boston, MA USA.
[Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, Epidemiol Branch, NIH, Bethesda, MD USA.
RP Hernan, MA (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA.
EM miguel_hernan@post.harvard.edu
OI Schisterman, Enrique/0000-0003-3757-641X
FU Intramural NIH HHS; NHLBI NIH HHS [R01 HL080644]; NIAID NIH HHS [R01
AI102634]
NR 16
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U1 1
U2 7
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 FEB 1
PY 2014
VL 179
IS 3
BP 368
EP 370
DI 10.1093/aje/kwt283
PG 3
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 296NA
UT WOS:000330190600012
PM 24287470
ER
PT J
AU OBrien, KM
Cole, SR
Poole, C
Bensen, JT
Herring, AH
Engel, LS
Millikan, RC
AF OBrien, Katie M.
Cole, Stephen R.
Poole, Charles
Bensen, Jeannette T.
Herring, Amy H.
Engel, Lawrence S.
Millikan, Robert C.
TI Replication of Breast Cancer Susceptibility Loci in Whites and African
Americans Using a Bayesian Approach
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE Bayesian analysis; breast cancer; genetics; genome-wide association
studies; GWAS replication; race; single nucleotide polymorphisms
ID GENOME-WIDE ASSOCIATION; GENETIC ASSOCIATION; POPULATION STRATIFICATION;
EPIDEMIOLOGIC RESEARCH; CONFER SUSCEPTIBILITY; COMMON VARIANTS;
CHROMOSOME 5P12; WOMENS HEALTH; RISK ALLELES; RECEPTOR
AB Genome-wide association studies (GWAS) and candidate gene analyses have led to the discovery of several dozen genetic polymorphisms associated with breast cancer susceptibility, many of which are considered well-established risk factors for the disease. Despite attempts to replicate these same variant-disease associations in African Americans, the evaluable populations are often too small to produce precise or consistent results. We estimated the associations between 83 previously identified single nucleotide polymorphisms (SNPs) and breast cancer among Carolina Breast Cancer Study (19932001) participants using maximum likelihood, Bayesian, and hierarchical methods. The selected SNPs were previous GWAS hits (n 22), near-hits (n 19), otherwise well-established risk loci (n 5), or located in the same genes as selected variants (n 37). We successfully replicated 18 GWAS-identified SNPs in whites (n 2,352) and 10 in African Americans (n 1,447). SNPs in the fibroblast growth factor receptor 2 gene (FGFR2) and the TOC high mobility group box family member 3 gene (TOX3) were strongly associated with breast cancer in both races. SNPs in the mitochondrial ribosomal protein S30 gene (MRPS30), mitogen-activated protein kinase kinase kinase 1 gene (MAP3K1), zinc finger, MIZ-type containing 1 gene (ZMIZ1), and H19, imprinted maternally expressed transcript gene (H19) were associated with breast cancer in whites, and SNPs in the estrogen receptor 1 gene (ESR1) and H19 gene were associated with breast cancer in African Americans. We provide precise and well-informed race-stratified odds ratios for key breast cancerrelated SNPs. Our results demonstrate the utility of Bayesian methods in genetic epidemiology and provide support for their application in small, etiologically driven investigations.
C1 [OBrien, Katie M.; Cole, Stephen R.; Poole, Charles; Bensen, Jeannette T.; Engel, Lawrence S.; Millikan, Robert C.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[OBrien, Katie M.; Bensen, Jeannette T.; Millikan, Robert C.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Herring, Amy H.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Biostat, Chapel Hill, NC USA.
[Herring, Amy H.] Univ N Carolina, Gillings Sch Global Publ Hlth, Carolina Populat Ctr, Chapel Hill, NC USA.
RP OBrien, KM (reprint author), NIEHS, Biostat Branch, POB 12233, Res Triangle Pk, NC 27709 USA.
EM obrienkm2@niehs.nih.gov
OI O'Brien, Katie/0000-0002-1931-1349; Engel, Lawrence/0000-0001-9268-4830
FU University Cancer Research Fund of North Carolina; National Cancer
Institute Specialized Program of Research Excellence in Breast Cancer
[NIH/NCI P50-CA58223]; Lineberger Comprehensive Cancer Center Core Grant
[NIH/NCI P30-CA16086]; Cancer Education and Career Development Program
institutional training grant; National Cancer Institute at the National
Institutes of Health [NIH/NCI 5R25CA057726-20]
FX This work was supported by the University Cancer Research Fund of North
Carolina, the National Cancer Institute Specialized Program of Research
Excellence in Breast Cancer (grant NIH/NCI P50-CA58223 to K.M.O.,
J.T.B., and R.C.M.), the Lineberger Comprehensive Cancer Center Core
Grant (NIH/NCI P30-CA16086 to K.M.O., J.T.B., and R.C.M.), and a Cancer
Education and Career Development Program institutional training grant
from the National Cancer Institute at the National Institutes of Health
(NIH/NCI 5R25CA057726-20 to K.M.O.).
NR 67
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U1 0
U2 16
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 FEB 1
PY 2014
VL 179
IS 3
BP 382
EP 394
DI 10.1093/aje/kwt258
PG 13
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 296NA
UT WOS:000330190600015
PM 24218030
ER
PT J
AU Caritis, SN
Venkataramanan, R
Thom, E
Harper, M
Klebanoff, MA
Sorokin, Y
Thorp, JM
Varner, MW
Wapner, RJ
Iams, JD
Carpenter, MW
Grobman, WA
Mercer, BM
Sciscione, A
Rouse, DJ
Ramin, S
AF Caritis, Steve N.
Venkataramanan, Raman
Thom, Elizabeth
Harper, Margaret
Klebanoff, Mark A.
Sorokin, Yoram
Thorp, John M., Jr.
Varner, Michael W.
Wapner, Ronald J.
Iams, Jay D.
Carpenter, Marshall W.
Grobman, William A.
Mercer, Brian M.
Sciscione, Anthony
Rouse, Dwight J.
Ramin, Susan
CA Eunice Kennedy Shriver Natl Inst C
Obstetric-Fetal Pharmacology Res U
TI Relationship between 17-alpha hydroxyprogesterone caproate concentration
and spontaneous preterm birth
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE dose response; pharmacodynamics; 17-hydroxyprogesterone caproate
concentration-response
ID 17-ALPHA-HYDROXYPROGESTERONE CAPROATE; PLASMA-CONCENTRATION; PREMATURE
LABOR; PREVENTION; PREGNANCY; DELIVERY
AB OBJECTIVE: 17-alpha hydroxyprogesterone caproate 250 mg weekly reduces recurrent spontaneous preterm birth in women with a prior spontaneous preterm birth by 33%. The dose is not based on pharmacologic considerations. A therapeutic concentration has not been determined hampering any attempt to optimize treatment. This study evaluated the relationship between 17-alpha hydroxyprogesterone caproate plasma concentrations and the rate of spontaneous preterm birth in women with singleton gestation.
STUDY DESIGN: A single blood sample was obtained between 25 and 28 weeks' gestation from 315 women with a spontaneous preterm birth who participated in a placebo-controlled, prospective, randomized clinical trial evaluating the benefit of omega-3 supplementation in reducing preterm birth. All women in the parent study received 17-alpha hydroxyprogesterone caproate and 434 received omega-3 supplementation and 418 received a placebo. Plasma from 315 consenting women was analyzed for 17-alpha hydroxyprogesterone caproate concentration.
RESULTS: There were no differences between placebo and omega-3 supplemented groups in demographic variables, outcomes or in mean 17-alpha hydroxyprogesterone caproate concentration. Plasma concentrations of 17-alpha hydroxyprogesterone caproate ranged from 3.7-56 ng/mL. Women with plasma concentrations of 17-alpha hydroxyprogesterone caproate in the lowest quartile had a significantly higher risk of spontaneous preterm birth (P = .03) and delivered at significantly earlier gestational ages (P = .002) than did women in the second to fourth quartiles. The lowest preterm birth rates were seen when median 17-alpha hydroxyprogesterone caproate concentrations exceeded 6.4 ng/mL.
CONCLUSION: Low plasma 17-alpha hydroxyprogesterone caproate concentration is associated with an increased risk of spontaneous preterm birth. This finding validates efficacy of this treatment but suggests that additional studies are needed to determine the optimal dosage.
C1 [Caritis, Steve N.; Venkataramanan, Raman] Univ Pittsburgh, Sch Med, Dept Obstet & Gynecol, Pittsburgh, PA 15260 USA.
[Caritis, Steve N.; Venkataramanan, Raman] Univ Pittsburgh, Sch Pharm, Dept Obstet & Gynecol, Pittsburgh, PA USA.
[Sciscione, Anthony] Drexel Univ, Coll Med, Philadelphia, PA 19104 USA.
[Thom, Elizabeth] George Washington Univ, Ctr Biostat, Washington, DC USA.
[Harper, Margaret; Thorp, John M., Jr.] Wake Forest Univ Hlth Sci, Dept Obstet & Gynecol, Winston Salem, NC USA.
[Sorokin, Yoram] Univ N Carolina, Chapel Hill, NC USA.
[Sorokin, Yoram] Wayne State Univ, Detroit, MI USA.
[Varner, Michael W.] Univ Utah, Hlth Sci Ctr, Salt Lake City, UT USA.
[Wapner, Ronald J.] Columbia Univ, Coll Phys & Surg, New York, NY USA.
[Iams, Jay D.] Ohio State Univ, Columbus, OH 43210 USA.
[Mercer, Brian M.] Case Western Reserve Univ, MetroHlth Med Ctr, Cleveland, OH 44106 USA.
[Carpenter, Marshall W.] Brown Univ, Women & Infants Hosp, Alpert Med Sch, Providence, RI USA.
[Grobman, William A.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Rouse, Dwight J.] Univ Alabama Birmingham, Med Sch Birmingham, Birmingham, AL USA.
[Ramin, Susan] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA.
[Klebanoff, Mark A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Maternal Fetal Med Units, Bethesda, MD USA.
RP Caritis, SN (reprint author), Univ Pittsburgh, Sch Med, Dept Obstet & Gynecol, Pittsburgh, PA 15260 USA.
RI Varner, Michael/K-9890-2013
OI caritis, steve/0000-0002-2169-0712; Varner, Michael/0000-0001-9455-3973
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD) [HD047905, HD27860, HD27917, HD40560, HD34208,
HD40485, HD21410, HD27915, HD40500, HD40512, HD40544, MO1-RR-000080,
HD34136, HD27869, HD40545, HD36801]
FX The project described was supported by grants from the Eunice Kennedy
Shriver National Institute of Child Health and Human Development (NICHD)
(HD047905, HD27860, HD27917, HD40560, HD34208, HD40485, HD21410,
HD27915, HD40500, HD40512, HD40544, MO1-RR-000080, HD34136, HD27869,
HD40545, HD36801) and does not necessarily represent the official views
of the NICHD or NIH.
NR 22
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U1 0
U2 6
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
EI 1097-6868
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD FEB
PY 2014
VL 210
IS 2
AR 128.e1
DI 10.1016/j.ajog.2013.10.008
PG 6
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 295OT
UT WOS:000330126100011
PM 24113254
ER
PT J
AU Laughon, SK
Albert, PS
Leishear, K
Mendola, P
AF Laughon, S. Katherine
Albert, Paul S.
Leishear, Kira
Mendola, Pauline
TI The NICHD Consecutive Pregnancies Study: recurrent preterm delivery by
subtype
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE indicated preterm birth; recurrent preterm birth; spontaneous preterm
birth
ID GESTATIONAL-AGE; RISK-FACTORS; BIRTH; PREDICTION; SINGLETON; WOMEN
AB OBJECTIVE: Attention for recurrent preterm delivery has primarily focused on spontaneous subtypes with less known about indicated preterm delivery.
STUDY DESIGN: In a retrospective cohort of consecutive pregnancies among 51,086 women in Utah (2002-2010), binary relative risk regression was performed to examine the risk of preterm delivery (PTD; <37 weeks) in the second observed delivery by PTD in the first, adjusting for maternal age, race/ethnicity, prepregnancy body mass index, insurance, smoking, alcohol and/or drug use, and chronic disease. Analyses were also performed stratified by prior preterm delivery subtype: spontaneous, indicated, or no recorded indication.
RESULTS: There were 3836 women who delivered preterm in the first observed pregnancy (7.6%), of which 1160 repeated in the second (30.7%). Rate of recurrent PTD was 31.6% for prior spontaneous, 23.0% for prior indicated delivery, and 27.4% for prior elective delivery. Prior spontaneous PTD was associated with a relative risk (RR) of 5.64 (95% confidence interval [CI], 5.27-6.05) of subsequent spontaneous and RR of 1.61 (95% CI, 0.98-2.67) of subsequent indicated PTD. Prior indicated PTD was associated with an RR of 9.10 (95% CI, 4.68-17.71) of subsequent indicated and RR of 2.70 (95% CI, 2.00-3.65) of subsequent spontaneous PTD.
CONCLUSION: Prior indicated PTD was strongly associated with subsequent indicated PTD and with increased risk for subsequent spontaneous PTD. Spontaneous PTD had the highest rate of recurrence. Some common pathways for different etiologies of preterm delivery are likely, and indicated PTD merits additional attention for recurrence risk.
C1 [Laughon, S. Katherine; Mendola, Pauline] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Div Intramural Populat Hlth Res, Epidemiol Branch, Rockville, MD 20852 USA.
[Albert, Paul S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Div Intramural Populat Hlth Res, Biostat Branch, Rockville, MD USA.
[Leishear, Kira] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Div Intramural Populat Hlth Res, Bioinformat Branches, Rockville, MD USA.
RP Laughon, SK (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Div Intramural Populat Hlth Res, Epidemiol Branch, Rockville, MD 20852 USA.
OI Mendola, Pauline/0000-0001-5330-2844; Grantz,
Katherine/0000-0003-0276-8534
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health [HHSN275200800002I,
HHSN27500004]
FX This study was supported by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, contract numbers
HHSN275200800002I and HHSN27500004.
NR 20
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U1 0
U2 6
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
EI 1097-6868
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD FEB
PY 2014
VL 210
IS 2
AR 131.e1
DI 10.1016/j.ajog.2013.09.014
PG 8
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 295OT
UT WOS:000330126100012
PM 24036403
ER
PT J
AU Snook, ER
Fisher-Perkins, JM
Sansing, HA
Lee, KM
Alvarez, X
MacLean, AG
Peterson, KE
Lackner, AA
Bunnell, BA
AF Snook, Eric R.
Fisher-Perkins, Jeanne M.
Sansing, Hope A.
Lee, Kim M.
Alvarez, Xavier
MacLean, Andrew G.
Peterson, Karin E.
Lackner, Andrew A.
Bunnell, Bruce A.
TI Innate Immune Activation in the Pathogenesis of a Murine Model of
Globoid Cell Leukodystrophy
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID CENTRAL-NERVOUS-SYSTEM; TOLL-LIKE RECEPTORS; PSYCHOSINE-INDUCED
APOPTOSIS; MULTIPLE-SCLEROSIS; KRABBE-DISEASE; TWITCHER MICE;
SPINAL-CORD; BRAIN; TLR2; EXPRESSION
AB Globoid cell leukodystrophy is a Lysosomat storage disease characterized by the Loss of galactocere-brosidase. Galactocerebrosidase Loss leads to the accumulation of psychosine and subsequent oligo-dendrocyte cell death, demyelination, macrophage recruitment, and astroglial activation and proliferation. To date, no studies have elucidated the mechanism of glial cell activation and cytokine and chemokine up-regulation and release. We explored a novel explanation for the development of the pathological changes in the early stages of globoid cell Leukodystrophy associated with toll-like receptor (TLR) 2 up-regulation in the hindbrain and cerebellum as a response to dying oligodendrocytes. TLR2 up-regulation on microglia/macrophages coincided with morphological changes consistent with activation at 2 and 3 weeks of age. TLR2 up-regulation on activated microglia/macrophages resulted in astrocyte activation and marked up-regulation of cytokines/chemokines. Because oligodendrocyte cell death is an important feature of globoid cell Leukodystrophy, we tested the ability of TLR2 reporter cells to respond to oligodendrocyte cell death. These reporter cells responded in vitro to medium conditioned by psychosine-treated oligodendrocytes, indicating the likelihood that oligodendrocytes release a TLR2 ligand during apoptosis. TLRs are a member of the innate immune system and initiate immune and inflammatory events; therefore, the identification of TLR2 as a potential driver in the activation of central nervous system glial activity in globoid cell Leukodystrophy may provide important insight into its pathogenesis.
C1 [Snook, Eric R.; Fisher-Perkins, Jeanne M.; Bunnell, Bruce A.] Tulane Natl Primate Res Ctr, Div Regenerat Med, Covington, LA 70433 USA.
[Sansing, Hope A.; Lee, Kim M.; Alvarez, Xavier; MacLean, Andrew G.; Lackner, Andrew A.] Tulane Natl Primate Res Ctr, Div Comparat Pathol, Covington, LA 70433 USA.
[Peterson, Karin E.] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, Hamilton, MT USA.
[Bunnell, Bruce A.] Tulane Univ, Hlth Sci Ctr, Dept Pharmacol, New Orleans, LA 70118 USA.
RP Bunnell, BA (reprint author), Tulane Natl Primate Res Ctr, 18703 Three Rivers Rd, Covington, LA 70433 USA.
EM bbunnell@tulane.edu
RI Peterson, Karin/D-1492-2016;
OI Peterson, Karin/0000-0003-4177-7249; Lee, Kim/0000-0002-5675-1896
FU National Center for Research Resources, NIH [P51 OD011104, T32
RR021309]; Tulane University grants
FX Supported in part by the National Center for Research Resources, NIH,
grants P51 OD011104 (Tulane National Primate Research Center) and T32
RR021309 (ES.) and Tulane University grants.
NR 67
TC 13
Z9 13
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9440
EI 1525-2191
J9 AM J PATHOL
JI Am. J. Pathol.
PD FEB
PY 2014
VL 184
IS 2
BP 382
EP 396
DI 10.1016/j.ajpath.2013.10.011
PG 15
WC Pathology
SC Pathology
GA 297LU
UT WOS:000330257700010
PM 24316110
ER
PT J
AU Greischar, MA
Read, AF
Bjornstad, ON
AF Greischar, Megan A.
Read, Andrew F.
Bjornstad, Ottar N.
TI Synchrony in Malaria Infections: How Intensifying Within-Host
Competition Can Be Adaptive
SO AMERICAN NATURALIST
LA English
DT Article
DE synchrony; malaria; interference competition; saturating immunity;
transmission; Jensen's inequality
ID PLASMODIUM-FALCIPARUM GAMETOCYTES; REPRODUCTIVE RESTRAINT;
ANOPHELES-GAMBIAE; PARASITES; DYNAMICS; EVOLUTION; BLOOD; CHEMOTHERAPY;
ERYTHROCYTES; EPIDEMIOLOGY
AB Malaria parasites exhibit great diversity in the coordination of their asexual life cycle within the host, ranging from asynchronous growth to tightly synchronized cycles of invasion and emergence from red blood cells. Synchronized reproduction should come at a high costintensifying competition among offspringso why would some Plasmodium species engage in such behavior and others not? We use a delayed differential equation model to show that synchronized infections can be favored when (1) there is limited interference among parasites competing for red blood cells, (2) transmission success is an accelerating function of sexual parasite abundance, (3) the target of saturating immunity is short-lived, and (4) coinfections with asynchronous parasites are rare. As a consequence, synchrony may be beneficial or costly, in line with the diverse patterns of synchronization observed in natural and lab infections. By allowing us to characterize diverse temporal dynamics, the model framework provides a basis for making predictions about disease severity and for projecting evolutionary responses to interventions.
C1 [Greischar, Megan A.; Read, Andrew F.; Bjornstad, Ottar N.] Penn State Univ, Dept Entomol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
[Greischar, Megan A.; Read, Andrew F.; Bjornstad, Ottar N.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
[Read, Andrew F.; Bjornstad, Ottar N.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Greischar, MA (reprint author), Penn State Univ, Dept Entomol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
EM mag450@psu.edu
FU National Institute of General Medical Sciences, NIH [R01GM089932]; Bill
and Melinda Gates Foundation
FX We wish to thank L. Beck-Johnson and W. A. Nelson for their assistance
with delay-differential equation techniques, S. Huijben for helpful
discussion, and F. E. McKenzie and N. Mideo for invaluable comments on
earlier drafts of the manuscript. We also thank members of the Research
and Policy in Infectious Disease Dynamics Program of the Science and
Technology Directorate, Department of Homeland Security, and the Fogarty
International Center, National Institutes of Health (NIH), for
stimulating discussion. This study was funded by the National Institute
of General Medical Sciences, NIH grants R01GM089932 (A.F.R.), and the
Bill and Melinda Gates Foundation (O.N.B.). The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the Fogarty International Center, the National
Institute of General Medical Sciences, the National Institutes of
Health, or the Gates Foundation.
NR 67
TC 7
Z9 7
U1 0
U2 19
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0003-0147
EI 1537-5323
J9 AM NAT
JI Am. Nat.
PD FEB 1
PY 2014
VL 183
IS 2
BP E36
EP E49
DI 10.1086/674357
PG 14
WC Ecology; Evolutionary Biology
SC Environmental Sciences & Ecology; Evolutionary Biology
GA 295AG
UT WOS:000330088400001
PM 24464205
ER
PT J
AU Painter, TO
Kaszas, K
Gross, J
Douglas, JT
Day, VW
Iadarola, MJ
Santini, C
AF Painter, Thomas O.
Kaszas, Krisztian
Gross, Jacklyn
Douglas, Justin T.
Day, Victor W.
Iadarola, Michael J.
Santini, Conrad
TI Constrained TRPV1 agonists synthesized via silver-mediated
intramolecular azo-methine ylide cycloaddition of alpha-iminoamides
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Chronic pain; Peripheral nerve ion channels; Intramolecular
cycloaddition; TRPV1 agonists
ID X=Y-ZH SYSTEMS; VANILLOID RECEPTOR TRPV1; POTENTIAL 1,3-DIPOLES;
AZOMETHINE YLIDES; ANALGESIC AGENTS; CAPSAICIN RECEPTOR; PAIN PATHWAY;
RESINIFERATOXIN; ANALOGS; IMINES
AB As part of an effort to identify agonists of TRPV1, a peripheral sensory nerve ion channel, high throughput screening of the NIH Small Molecule Repository (SMR) collection identified MLS002174161, a pentacyclic benzodiazepine. A synthesis effort was initiated that ultimately afforded racemic seco analogs 12 of the SMR compound via a silver mediated intramolecular [3+2] cycloaddition of an azo-methine ylide generated from alpha-iminoamides 11. The cycloaddition set four contiguous stereocenters and, in some cases, also spontaneously afforded imides 13 from 12. The synthesis of compounds 12, the features that facilitated the conversion of 12-13, and their partial agonist activity against TRPV1 are discussed. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Painter, Thomas O.; Santini, Conrad] Univ Kansas, Ctr Chem Methodol & Lib Dev, Lawrence, KS 66047 USA.
[Kaszas, Krisztian; Gross, Jacklyn; Iadarola, Michael J.] NIH, Dept Perioperat Med, Ctr Clin, Bethesda, MD 20892 USA.
[Douglas, Justin T.; Day, Victor W.] Univ Kansas, Mol Struct Grp, Lawrence, KS 66045 USA.
RP Santini, C (reprint author), 24780 Chieftain Rd, Lawrence, KS 66044 USA.
EM nyprphd@yahoo.com
FU KU-CMLD under NIGMS Grant [5P50GM069663]; KU-NMR Center [NIH
1S10RR024664-01]; NSF-MRI Grant [CHE-0923449]; NIMH Grant [1 R03
MH089480-01]; Division of Intramural Research, NIDCR, NIH; Department of
Perioperative Medicine, Clinical Center, NIH
FX We acknowledge Mr. Patrick Porubsky, KU-CMLD Purification Chemist and
Compound Curator. Financial support for the KU-CMLD was provided under
NIGMS Grant #5P50GM069663 (Prof. Jeff Aube, PI). Support for the KU-NMR
Center (JTD) was provided under Grant #NIH 1S10RR024664-01. Support for
the KU-X-Ray facility (VWD) was provided under NSF-MRI Grant
CHE-0923449. Support for the HTS screen was provided by NIMH Grant # 1
R03 MH089480-01 (M. Iadarola); research was also supported by the
Division of Intramural Research, NIDCR, NIH and the Department of
Perioperative Medicine, Clinical Center, NIH. The funding sources did
not participate in the design of the work described in this report.
NR 44
TC 1
Z9 1
U1 1
U2 11
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
EI 1464-3405
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD FEB 1
PY 2014
VL 24
IS 3
BP 963
EP 968
DI 10.1016/j.bmcl.2013.12.061
PG 6
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 295MS
UT WOS:000330120800047
PM 24412067
ER
PT J
AU Victorson, D
Cavazos, JE
Holmes, GL
Reder, AT
Wojna, V
Nowinski, C
Miller, D
Buono, S
Mueller, A
Moy, C
Cella, D
AF Victorson, David
Cavazos, Jose E.
Holmes, Gregory L.
Reder, Anthony T.
Wojna, Valerie
Nowinski, Cindy
Miller, Deborah
Buono, Sarah
Mueller, Allison
Moy, Claudia
Cella, David
TI Validity of the Neurology Quality-of-Life (Neuro-QoL) measurement system
in adult epilepsy
SO EPILEPSY & BEHAVIOR
LA English
DT Article
DE Epilepsy; Quality of life; Neuro-QoL; Measurement; Psychometrics;
Validation
ID SEIZURE SEVERITY SCALE; HEALTH-STATUS; INSTRUMENTS; ITEM; DETERMINANTS;
RELIABILITY; SURGERY; STROKE; STIGMA; EQ-5D
AB Epilepsy is a chronic neurological disorder that results in recurring seizures and can have a significant adverse effect on health-related quality of life (HRQL). The Neuro-QoL measurement initiative is an NINDS-funded system of patient-reported outcome measures for neurology clinical research, which was designed to provide a precise and standardized way to measure HRQL in epilepsy and other neurological disorders. Using mixed-method and item response theory-based approaches, we developed generic item banks and targeted scales for adults and children with major neurological disorders. This paper provides empirical results from a clinical validation study with a sample of adults diagnosed with epilepsy. One hundred twenty-one people diagnosed with epilepsy participated, the majority of which were male (62%) and Caucasian (95%), with a mean age of 47.3 (SD = 16.9). Baseline assessments included Neuro-QoL short forms and general and external validity measures. The Neuro-QoL short forms that are not typically found in other epilepsy-specific HRQL instruments include Stigma, Sleep Disturbance, Emotional and Behavioral Dyscontrol, and Positive Affect and Well-Being. Neurology Quality-of-Life short forms demonstrated adequate reliability (internal consistency range =.86-. 96; test-retest range =.57-. 89). Pearson correlations (p < .01) between Neuro-QoL forms of emotional distress (anxiety, depression, stigma) and the QOLIE-31 Emotional Well-Being subscale were in the moderate-to-strong range (r's =.66,.71 and.53, respectively), as were relations with the PROMIS Global Mental Health subscale (r's =.59,.74 and.52, respectively). Moderate correlations were observed between Neuro-QoL Social Role Performance and Satisfaction and the QOLIE-31 Social Function (r's =.58 and.52, respectively). In measuring aspects of physical function, the Neuro-QoL Mobility and Upper Extremity forms demonstrated moderate associations with the PROMIS Global Physical Function subscale (r's =.60 and.61, respectively). Neuro-QoL measures of perceived cognitive function (executive function and general concerns) produced moderate-to-strong correlations with the QOLIE-31 Cognition subscale (r's =.65 and.75, respectively) and moderate relations with the Liverpool Adverse Events Profile (r's =.51 and.69, respectively). Finally, the Neuro-QoL Fatigue measure demonstrated moderate associations with the QOLIE-31 Energy/Fatigue subscale (r = -. 65), Liverpool Adverse Events Profile (r =.69), and the Liverpool Seizure Severity Scale (r =.50). Five Neuro-QoL short forms demonstrated statistically significant responsiveness to change at 5-7 months, including Fatigue, Sleep Disturbance, Depression, Positive Affect and Well-Being, and Emotional and Behavioral Dyscontrol. Overall, Neuro-QoL instruments showed good evidence for internal consistency, test-retest reliability, convergent validity, and responsiveness to change over several months. These results support the validity of Neuro-QoL to measure HRQL in adults with epilepsy. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Victorson, David; Nowinski, Cindy; Buono, Sarah; Mueller, Allison; Cella, David] Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, Evanston, IL 60208 USA.
[Cavazos, Jose E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Neurol, San Antonio, TX 78229 USA.
[Holmes, Gregory L.] Univ Vermont, Coll Med, Dept Neurol Sci, Burlington, VT USA.
[Reder, Anthony T.] Univ Chicago, Dept Neurol, Chicago, IL 60637 USA.
[Wojna, Valerie] Univ Puerto Rico, Div Neurol, Dept Internal Med, San Juan, PR 00936 USA.
[Miller, Deborah] Cleveland Clin Fdn, Mellen Ctr, Cleveland, OH 44195 USA.
[Moy, Claudia] NINDS, Bethesda, MD 20892 USA.
RP Victorson, D (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, Hogan Bldg,2205 Tech Dr,Suite 2-120, Evanston, IL 60208 USA.
EM d-victorson@northwestern.edu; CAVAZOSJ@uthscsa.edu;
gregory.holmes@uvm.edu; areder@neurology.bsd.uchicago.edu;
valerie.wojna1@upr.edu; c-nowinski@northwestern.edu; MillerD@ccf.org;
sarah-buono@northwestern.edu; amuelle4@uic.edu; MoyC@ninds.nih.gov;
d-cella@northwestern.edu
RI Cavazos, Jose/J-4122-2016;
OI Cavazos, Jose/0000-0001-5777-2608; Wojna, Valerie/0000-0002-4014-9921
FU National Institute for Neurological Disorders and Stroke [HHSN
2652004236-01C, HHSN 271201200036C-0-0-1]
FX Supported by the National Institute for Neurological Disorders and
Stroke contracts HHSN 2652004236-01C and HHSN 271201200036C-0-0-1. The
contents represent original work and have not been published elsewhere.
No commercial party having a direct financial interest in the results of
the research supporting this article has or will confer a benefit upon
the author(s) or upon any organization with which the author(s) is/are
associated.
NR 61
TC 4
Z9 4
U1 2
U2 10
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1525-5050
EI 1525-5069
J9 EPILEPSY BEHAV
JI Epilepsy Behav.
PD FEB
PY 2014
VL 31
BP 77
EP 84
DI 10.1016/j.yebeh.2013.11.008
PG 8
WC Behavioral Sciences; Clinical Neurology; Psychiatry
SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry
GA 296NV
UT WOS:000330192700018
PM 24361767
ER
PT J
AU Zheng, HP
Hou, J
Zimmerman, MD
Wlodawer, A
Minor, W
AF Zheng, Heping
Hou, Jing
Zimmerman, Matthew D.
Wlodawer, Alexander
Minor, Wladek
TI The future of crystallography in drug discovery
SO EXPERT OPINION ON DRUG DISCOVERY
LA English
DT Review
DE Big Data; crystallographic data interpretation; functional annotation;
protein crystallography; target-based drug discovery; validation;
virtual screening
ID PROTEIN DATA-BANK; CURRENT TRENDS; STRUCTURAL GENOMICS; DIFFRACTION
IMAGES; CRYSTAL-STRUCTURES; ELECTRON-DENSITY; LIGAND DOCKING; BIG DATA;
DESIGN; VALIDATION
AB Introduction: X-ray crystallography plays an important role in structure-based drug design (SBDD), and accurate analysis of crystal structures of target macromolecules and macromolecule-ligand complexes is critical at all stages. However, whereas there has been significant progress in improving methods of structural biology, particularly in X-ray crystallography, corresponding progress in the development of computational methods (such as in silico high-throughput screening) is still on the horizon. Crystal structures can be overinterpreted and thus bias hypotheses and follow-up experiments. As in any experimental science, the models of macromolecular structures derived from X-ray diffraction data have their limitations, which need to be critically evaluated and well understood for structure-based drug discovery.
Areas covered: This review describes how the validity, accuracy and precision of a protein or nucleic acid structure determined by X-ray crystallography can be evaluated from three different perspectives: i) the nature of the diffraction experiment; ii) the interpretation of an electron density map; and iii) the interpretation of the structural model in terms of function and mechanism. The strategies to optimally exploit a macromolecular structure are also discussed in the context of 'Big Data' analysis, biochemical experimental design and structure-based drug discovery.
Expert opinion: Although X-ray crystallography is one of the most detailed 'microscopes' available today for examining macromolecular structures, the authors would like to re-emphasize that such structures are only simplified models of the target macromolecules. The authors also wish to reinforce the idea that a structure should not be thought of as a set of precise coordinates but rather as a framework for generating hypotheses to be explored. Numerous biochemical and biophysical experiments, including new diffraction experiments, can and should be performed to verify or falsify these hypotheses. X-ray crystallography will find its future application in drug discovery by the development of specific tools that would allow realistic interpretation of the outcome coordinates and/or support testing of these hypotheses.
C1 [Zheng, Heping; Hou, Jing; Zimmerman, Matthew D.; Minor, Wladek] Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA.
[Wlodawer, Alexander] NCI, Ctr Canc Res, Frederick, MD 21702 USA.
[Zheng, Heping; Hou, Jing; Zimmerman, Matthew D.; Minor, Wladek] CSGID, Bethesda, MD USA.
[Hou, Jing; Zimmerman, Matthew D.; Minor, Wladek] Enzyme Struct Initiat EFI, Urbana, IL USA.
[Zheng, Heping; Zimmerman, Matthew D.; Minor, Wladek] MCSG, Mesa, AZ USA.
[Zheng, Heping; Hou, Jing; Zimmerman, Matthew D.; Minor, Wladek] NYSGRC, New York, NY USA.
RP Minor, W (reprint author), Univ Virginia, Dept Mol Physiol & Biol Phys, 1340 Jefferson Pk Ave, Charlottesville, VA 22908 USA.
EM wladek@iwonka.med.virginia.edu
RI Minor, Wladek/F-3096-2014; Zimmerman, Matthew/N-9489-2013;
OI Zimmerman, Matthew/0000-0002-6274-9493; Minor,
Wladek/0000-0001-7075-7090
FU National Institute of Allergy and Infectious Diseases; National
Institutes of Health; Department of Health and Human Services
[HHSN272201200026C]; NIH [GM094662, GM093342, GM094585]; Intramural
Research Program of the NIH, National Cancer Institute; Center for
Cancer Research
FX The authors' research was supported by federal funds from the National
Institute of Allergy and Infectious Diseases, National Institutes of
Health, Department of Health and Human Services, under Contract No.
HHSN272201200026C, by NIH grants GM094662, GM093342 and GM094585, and in
part by the Intramural Research Program of the NIH, National Cancer
Institute, Center for Cancer Research. The authors state no conflict of
interest in preparation of this manuscript.
NR 77
TC 10
Z9 10
U1 0
U2 63
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1746-0441
EI 1746-045X
J9 EXPERT OPIN DRUG DIS
JI Expert. Opin. Drug Discov.
PD FEB
PY 2014
VL 9
IS 2
BP 125
EP 137
DI 10.1517/17460441.2014.872623
PG 13
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 294VA
UT WOS:000330074400003
PM 24372145
ER
PT J
AU Lin, HH
Dolmatova, EV
Morley, MP
Lunetta, KL
McManus, DD
Magnani, JW
Margulies, KB
Hakonarson, H
del Monte, F
Benjamin, EJ
Cappola, TP
Ellinor, PT
AF Lin, Honghuang
Dolmatova, Elena V.
Morley, Michael P.
Lunetta, Kathryn L.
McManus, David D.
Magnani, Jared W.
Margulies, Kenneth B.
Hakonarson, Hakon
del Monte, Federica
Benjamin, Emelia J.
Cappola, Thomas P.
Ellinor, Patrick T.
TI Gene expression and genetic variation in human atria
SO HEART RHYTHM
LA English
DT Article
DE Genetics; Expression quantitative trait loci; Gene expression; Atrial
tissue
ID GENOME-WIDE ASSOCIATION; HEART-FAILURE; FIBRILLATION; DISEASE;
OVEREXPRESSION; DYSFUNCTION; DISCOVERY; INTERVAL; BINDING; PROTEIN
AB BACKGROUND The human left and right atria have different susceptibilities to develop atrial fibrillation (AF). However, the molecular events related to structural and functional changes that enhance AF susceptibility are still poorly understood.
OBJECTIVE The purpose of this study was to characterize gene expression and genetic variation in human atria.
METHODS We studied the gene expression profiles and genetic variations in 53 left atrial and 52 right atrial tissue samples collected from the Myocardial Applied Genomics Network (MAGNet) repository. The tissues were collected from heart failure patients undergoing transplantation and from unused organ donor hearts with normal ventricular function. Gene expression was profiled using the Affymetrix GeneChip Human Genome U133A Array. Genetic variation was profiled using the Affymetrix Genome-Wide Human SNP Array 6.0.
RESULTS We found that 109 genes were differentially expressed between left and right atrial tissues. A total of 187 and 259 significant cis-associations between transcript levels and genetic variants were identified in left and right atrial tissues, respectively. We also found that a single nucleotide polymorphism at a known AF locus, rs3740293, was associated with the expression of MYOZ1 in both left and right atrial tissues.
CONCLUSION We found a distinct transcriptional profile between the right and left atrium and extensive cis-associations between atrial transcripts and common genetic variants. Our results implicate MYOZ1 as the causative gene at the chromosome 10q22 locus for AF.
C1 [Lin, Honghuang; Lunetta, Kathryn L.; McManus, David D.; Magnani, Jared W.; Benjamin, Emelia J.] Natl Heart Lung & Blood Inst & Boston Univ Framin, Framingham, MA USA.
[Lin, Honghuang] Boston Univ, Sch Med, Dept Med, Sect Computat Biomed, Boston, MA 02118 USA.
[McManus, David D.] Univ Massachusetts, Sch Med, Dept Med, Div Cardiol, Worcester, MA USA.
[McManus, David D.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Div Epidemiol, Worcester, MA USA.
[Morley, Michael P.; Margulies, Kenneth B.; Hakonarson, Hakon; Cappola, Thomas P.] Univ Penn, Sch Med, Penn Cardiovasc Inst, Philadelphia, PA 19104 USA.
[Lunetta, Kathryn L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
[Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Sect Cardiovasc Med, Boston, MA 02118 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Sect Prevent Med, Boston, MA 02118 USA.
[Dolmatova, Elena V.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA.
[Ellinor, Patrick T.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[del Monte, Federica] Beth Israel Deaconess Med Ctr, Cardiovasc Inst, Boston, MA 02215 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA.
[Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
[Ellinor, Patrick T.] Harvard Univ, Sch Med, Boston, MA USA.
RP Lin, HH (reprint author), Boston Univ, Sch Med, Dept Med, Sect Computat Biomed, 72 East Concord St,B-616, Boston, MA 02118 USA.
EM hhlin@bu.edu
OI Lin, Honghuang/0000-0003-3043-3942; Benjamin, Emelia/0000-0003-4076-2336
FU National Institutes of Health [R01HL092577, 1R01 HL102214, R01HL104156,
K24HL105780, R01HL105993, KL2RR031981, 1U01HL105268-01]; American Heart
Association [13EIA14220013, 09FTF2190028]
FX This work is supported by National Institutes of Health Grant
R01HL092577 to Drs. Ellinor and Benjamin, 1R01 HL102214 to Dr. Benjamin,
R01HL104156 and K24HL105780 to Dr. Ellinor, R01HL105993 to Dr. Margulies
and Cappola, and KL2RR031981 and 1U01HL105268-01 to Dr. McManus; and
American Heart Association Award 13EIA14220013 to Dr. Ellinor and
09FTF2190028 to Dr. Magnani.
NR 42
TC 12
Z9 12
U1 0
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1547-5271
EI 1556-3871
J9 HEART RHYTHM
JI Heart Rhythm
PD FEB
PY 2014
VL 11
IS 2
BP 266
EP 271
DI 10.1016/j.hrthm.2013.10.051
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 296MR
UT WOS:000330189700015
PM 24177373
ER
PT J
AU Hoofnagle, JH
AF Hoofnagle, Jay H.
TI Introducing the AASLD President: Adrian Di Bisceglie
SO HEPATOLOGY
LA English
DT Biographical-Item
C1 NIDDK, Div Digest Dis & Nutr, NIH, Bethesda, MD 20852 USA.
RP Hoofnagle, JH (reprint author), NIDDK, Div Digest Dis & Nutr, NIH, 6707 Democracy Blvd,Room 655, Bethesda, MD 20852 USA.
EM HoofnagleJ@extra.niddk.nih.gov
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 0270-9139
EI 1527-3350
J9 HEPATOLOGY
JI Hepatology
PD FEB
PY 2014
VL 59
IS 2
BP 360
EP 362
DI 10.1002/hep.26917
PG 3
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 298FT
UT WOS:000330310300001
PM 24353092
ER
PT J
AU Kleiner, DE
Chalasani, NP
Lee, WM
Fontana, RJ
Bonkovsky, HL
Watkins, PB
Hayashi, PH
Davern, TJ
Navarro, V
Reddy, R
Talwalkar, JA
Stolz, A
Gu, JZ
Barnhart, H
Hoofnagle, JH
AF Kleiner, David E.
Chalasani, Naga P.
Lee, William M.
Fontana, Robert J.
Bonkovsky, Herbert L.
Watkins, Paul B.
Hayashi, Paul H.
Davern, Timothy J.
Navarro, Victor
Reddy, Rajender
Talwalkar, Jayant A.
Stolz, Andrew
Gu, Jiezhun
Barnhart, Huiman
Hoofnagle, Jay H.
CA DILIN
TI Hepatic Histological Findings in Suspected Drug-Induced Liver Injury:
Systematic Evaluation and Clinical Associations
SO HEPATOLOGY
LA English
DT Article
ID CAUSALITY ASSESSMENT; ADVERSE REACTIONS; UNITED-STATES; DISEASE;
NITROFURANTOIN
AB Drug-induced liver injury (DILI) is considered to be a diagnosis of exclusion. Liver biopsy may contribute to diagnostic accuracy, but the histological features of DILI and their relationship to biochemical parameters and outcomes are not well defined. We have classified the pathological pattern of liver injury and systematically evaluated histological changes in liver biopsies obtained from 249 patients with suspected DILI enrolled in the prospective, observational study conducted by the Drug Induced Liver Injury Network. Histological features were analyzed for their frequency within different clinical phenotypes of liver injury and to identify associations between clinical and laboratory findings and histological features. The most common histological patterns were acute (21%) and chronic hepatitis (14%), acute (9%) and chronic cholestasis (10%), and cholestatic hepatitis (29%). Liver histology from 128 patients presenting with hepatocellular injury had more severe inflammation, necrosis, and apoptosis and more frequently demonstrated lobular disarray, rosette formation, and hemorrhage than those with cholestasis. Conversely, histology of the 73 patients with cholestatic injury more often demonstrated bile plugs and duct paucity. Severe or fatal hepatic injury in 46 patients was associated with higher degrees of necrosis, fibrosis stage, microvesicular steatosis, and ductular reaction among other findings, whereas eosinophils and granulomas were found more often in those with milder injury. Conclusion: We describe an approach for evaluating liver histology in DILI and demonstrate numerous associations between pathological findings and clinical presentations that may serve as a foundation for future studies correlating DILI pathology with its causality and outcome.
C1 [Kleiner, David E.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Chalasani, Naga P.] Indiana Univ, Indianapolis, IN 46204 USA.
[Lee, William M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Fontana, Robert J.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Bonkovsky, Herbert L.] Carolinas Med Ctr, Charlotte, NC 28203 USA.
[Watkins, Paul B.; Hayashi, Paul H.] Univ N Carolina, Chapel Hill, NC USA.
[Davern, Timothy J.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Navarro, Victor] Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA.
[Reddy, Rajender] Univ Penn, Philadelphia, PA 19104 USA.
[Talwalkar, Jayant A.] Mayo Clin, Coll Med, Rochester, MN USA.
[Stolz, Andrew] Univ So Calif, Los Angeles, CA USA.
[Gu, Jiezhun; Barnhart, Huiman] Duke Clin Res Inst, Durham, NC USA.
[Hoofnagle, Jay H.] NIDDK, Liver Dis Res Branch, Div Digest Dis & Nutrt, NIH, Bethesda, MD 20892 USA.
RP Kleiner, DE (reprint author), NCI, Pathol Lab, Bldg 10,Room 2B50,MSC 1500,10 Ctr Dr, Bethesda, MD 20892 USA.
EM kleinerd@mail.nih.gov
OI Kleiner, David/0000-0003-3442-4453
FU National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK); National Institutes of Health (NIH) [U01DK065193, U01DK065211,
U01DK065238, U01DK065184, U01DK065201, U01DK83023, U01DK083020,
U01DK08992, U01DK083027, U01DK065176]; Intramural Program of the
National Cancer Institute, National Institutes of Health
FX The DILIN network is structured as an U01 cooperative agreement
supported by the National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK) and the National Institutes of Health (NIH) with funds
provided by the following grants: U01DK065193 (University of
Connecticut); U01DK065211 (University of Indiana [Purdue]); U01DK065238
(University of California San Francisco/CPMC); U01DK065184 (University
of Michigan [Ann Arbor]); U01DK065201 (University of North Carolina
Chapel Hill, Asheville, Carolinas Medical Center, Duke); U01DK83023
(University of Texas-Southwestern); U01DK083020 (University of Southern
California, UCLA Pfleger Liver Institute); U01DK08992 (Mayo Clinic);
U01DK083027 (Thomas Jefferson and University of Pennsylvania); and
U01DK065176 (Duke Clinical Research Institute as Data Coordinating
Center). This work was supported, in part, by the Intramural Program of
the National Cancer Institute, National Institutes of Health. This study
is DILIN publication no. 23.
NR 22
TC 53
Z9 58
U1 4
U2 18
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-9139
EI 1527-3350
J9 HEPATOLOGY
JI Hepatology
PD FEB
PY 2014
VL 59
IS 2
BP 661
EP 670
DI 10.1002/hep.26709
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 298FT
UT WOS:000330310300032
PM 24037963
ER
PT J
AU Kim, JH
Qu, AJ
Reddy, JK
Gao, B
Gonzalez, FJ
AF Kim, Jung-Hwan
Qu, Aijuan
Reddy, Janardan K.
Gao, Bin
Gonzalez, Frank J.
TI Hepatic Oxidative Stress Activates the Gadd45b Gene by Way of
Degradation of the Transcriptional Repressor STAT3
SO HEPATOLOGY
LA English
DT Article
ID NF-KAPPA-B; PPAR-ALPHA; HYDROGEN-PEROXIDE; IKK-BETA; CELLS; APOPTOSIS;
PROMOTER; LIVER; HEPATOCARCINOGENESIS; PROLIFERATION
AB Growth arrest and DNA damage-inducible beta (GADD45b) plays an important role in many intracellular events, such as cell cycle arrest, DNA repair, cell survival, apoptosis, and senescence. However, its mechanism of transcriptional regulation remains unclear. In this study the mechanism of peroxisome proliferator-activated receptor (PPAR) ligand induction of the Gadd45b gene in mouse liver was investigated. Gadd45b messenger RNA (mRNA) was markedly induced by the PPAR agonist Wy-14,643 in wild-type mice but not in Ppara-null mice. Signal transducer and activator of transcription 3 (STAT3) was found to be a repressor of the Gadd45b gene through binding to upstream regulatory elements. The role of STAT3 in control of Gadd45b was confirmed using liver-specific Stat3-null mice. Wy-14,643 treatment stimulated STAT3 ubiquitination leading to activation of the Gadd45b gene as a result of loss of Gadd45b repression by STAT3. STAT3 degradation was induced by forced overexpression of the PPAR target gene-encoded enzyme ACOX1, which produces increased H2O2 as a byproduct of fatty acid -oxidation. H2O2 also stimulated expression of Gadd45b in cultured cells. Conclusion: PPAR indirectly induces the Gadd45b gene in liver through promoting degradation of the repressor STAT3 as a result of elevated oxidative stress.
C1 [Kim, Jung-Hwan; Qu, Aijuan; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Reddy, Janardan K.] Northwestern Univ, Dept Pathol, Feinberg Sch Med, Chicago, IL 60611 USA.
[Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD USA.
RP Gonzalez, FJ (reprint author), NCI, Lab Metab, NIH, Bethesda, MD 20892 USA.
EM gonzalef@mail.nih.gov
FU National Cancer Institute Intramural Research Program
FX Supported by the National Cancer Institute Intramural Research Program.
NR 34
TC 17
Z9 18
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-9139
EI 1527-3350
J9 HEPATOLOGY
JI Hepatology
PD FEB
PY 2014
VL 59
IS 2
BP 695
EP 704
DI 10.1002/hep.26683
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 298FT
UT WOS:000330310300035
PM 23939942
ER
PT J
AU Dmitriev, P
Kairov, U
Robert, T
Barat, A
Lazar, V
Carnac, G
Laoudj-Chenivesse, D
Vassetzky, YS
AF Dmitriev, Petr
Kairov, Ulykbek
Robert, Thomas
Barat, Ana
Lazar, Vladimir
Carnac, Gilles
Laoudj-Chenivesse, Dalila
Vassetzky, Yegor S.
TI Cancer-related genes in the transcription signature of
facioscapulohumeral dystrophy myoblasts and myotubes
SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
LA English
DT Article
DE cancer; rhabdomyosarcoma; Ewing's sarcoma; FSHD; muscular dystrophy
ID DUCHENNE MUSCULAR-DYSTROPHY; ROUND-CELL SARCOMAS; MYOTONIC-DYSTROPHY;
EXPRESSION PROFILE; RHABDOMYOSARCOMA; DIFFERENTIATION; MECHANISMS;
FUSION; MODEL; MICE
AB Muscular dystrophy is a condition potentially predisposing for cancer; however, currently, only Myotonic dystrophy patients are known to have a higher risk of cancer. Here, we have searched for a link between facioscapulohumeral dystrophy (FSHD) and cancer by comparing published transcriptome signatures of FSHD and various malignant tumours and have found a significant enrichment of cancer-related genes among the genes differentially expressed in FSHD. The analysis has shown that gene expression profiles of FSHD myoblasts and myotubes resemble that of Ewing's sarcoma more than that of other cancer types tested. This is the first study demonstrating a similarity between FSHD and cancer cell expression profiles, a finding that might indicate the existence of a common step in the pathogenesis of these two diseases.
C1 [Dmitriev, Petr; Robert, Thomas; Barat, Ana; Lazar, Vladimir; Vassetzky, Yegor S.] Univ Paris 11, CNRS, Inst Cancerol Gustave Roussy, UMR8126, F-94805 Villejuif, France.
[Dmitriev, Petr; Carnac, Gilles; Laoudj-Chenivesse, Dalila] Univ Montpellier I, INSERM, U1046, Montpellier, France.
[Kairov, Ulykbek] Nazarbayev Univ, Dept Genom & Personalized Med, Ctr Life Sci, Astana, Kazakhstan.
[Kairov, Ulykbek] Natl Biotechnol Ctr, Natl Sci Shared Lab Biotechnol, Astana, Kazakhstan.
RP Vassetzky, YS (reprint author), Univ Paris 11, CNRS, Inst Cancerol Gustave Roussy, UMR8126, F-94805 Villejuif, France.
EM vassetzky@igr.fr
RI Kairov, Ulykbek/J-1625-2014; Kairov, Ulykbek/F-8855-2015; Vassetzky,
Yegor/C-6447-2008
OI Kairov, Ulykbek/0000-0001-8511-8064; Vassetzky,
Yegor/0000-0003-3101-7043
FU Association Francaise contre les Myopathies (AFM); IRC-SET-Marie Curie
International Mobility Fellowships in Science Engineering and
Technology, Ireland; Association "Amis FSH"; University Montpellier I
FX The research has been supported by grants from the Association Francaise
contre les Myopathies (AFM) to YSV and DL. AB was a recipient of the
IRC-SET-Marie Curie International Mobility Fellowships in Science
Engineering and Technology, Ireland. P.D. was supported by the
Association "Amis FSH" and the University Montpellier I. We thank Cecile
Cassan for critical reading of the manuscript.
NR 70
TC 3
Z9 3
U1 1
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1582-4934
J9 J CELL MOL MED
JI J. Cell. Mol. Med.
PD FEB
PY 2014
VL 18
IS 2
BP 208
EP 217
DI 10.1111/jcmm.12182
PG 10
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 296MW
UT WOS:000330190200003
PM 24341522
ER
PT J
AU Esnakula, AK
Ricks-Santi, L
Kwagyan, J
Kanaan, YM
DeWitty, RL
Wilson, LL
Gold, B
Frederick, WAI
Naab, TJ
AF Esnakula, Ashwini K.
Ricks-Santi, Luisel
Kwagyan, John
Kanaan, Yasmine M.
DeWitty, Robert L.
Wilson, Lori L.
Gold, Bert
Frederick, Wayne A. I.
Naab, Tammey J.
TI Strong association of fascin expression with triple negative breast
cancer and basal-like phenotype in African-American women
SO JOURNAL OF CLINICAL PATHOLOGY
LA English
DT Article
ID EPITHELIAL-MESENCHYMAL TRANSITION; ACTIN-BUNDLING PROTEIN; CELL
MOTILITY; SUBTYPES; PROGRESSION; POPULATION; PREVALENCE; SURVIVAL;
RECEPTOR; PREMENOPAUSAL
AB Background Fascin, an actin bundling protein, plays a critical role in cell motility due to formation of actin rich protrusions called filopodia, important in cell migration, invasion and metastatic spread. Fascin overexpression has been associated with epithelial to mesenchymal transition and correlates with progression and unfavourable prognosis in breast carcinoma.
Objective To evaluate fascin expression by immunohistochemistry and correlate the expression pattern with clinicopathological parameters in breast cancer in African-American (AA) women, in whom triple negative breast cancer (TNBC), an aggressive subtype, is more prevalent.
Methods Tissue microarrays were constructed from formalin-fixed, paraffin-embedded blocks of tumour tissue from primary breast carcinomas in 202 AA women. Immunohistochemical detection of fascin was correlated with four major subtypes of breast carcinoma (luminal A, luminal B, human epidermal growth factor receptor 2 and triple negative (TN)) and other clinicopathological factors, including age, grade, tumour size, stage, regional lymph node status and survival.
Results We observed a significant association between fascin expression and TN subtype, oestrogen receptor (ER) negativity, progesterone receptor (PR) negativity, Elston-Nottingham (EN) grade 3 and decreased overall survival. There was also a significant association between expression of CK 5/6, a marker of basal-like phenotype, and fascin expression.
Conclusion These results suggest that fascin is a marker for TN subtype having a basal-like phenotype and decreased overall survival. Fascin may represent a target for therapy in TNBC in AA women.
C1 [Esnakula, Ashwini K.; Naab, Tammey J.] Howard Univ Hosp, Dept Pathol, Washington, DC USA.
[Ricks-Santi, Luisel] Howard Univ, Coll Med, Dept Pediat & Child Hlth, Washington, DC 20060 USA.
[Kwagyan, John] Howard Univ, Coll Med, Dept Community & Family Med, Washington, DC 20060 USA.
[Kwagyan, John] Howard Univ, Coll Med, Georgetown Howard Univ Ctr Clin & Translat Sci, Washington, DC 20060 USA.
[Kanaan, Yasmine M.] Howard Univ, Coll Med, Dept Microbiol, Washington, DC 20060 USA.
[DeWitty, Robert L.; Wilson, Lori L.; Frederick, Wayne A. I.] Howard Univ Hosp, Dept Surg Oncol, Washington, DC USA.
[Gold, Bert] NCI, Expt Med Lab, Human Genet Sect, Frederick, MD 21701 USA.
RP Naab, TJ (reprint author), Howard Univ, Howard Univ Hosp, Coll Med, Dept Pathol, 2041 Georgia Ave NW, Washington, DC 20060 USA.
EM tnaab@huhosp.org
FU National Center for Research Resources [NCRR-UL1RR031975]; National
Institutes of Health, through the Clinical and Translational Science
Awards Program (CTSA), a trademark of DHHS, part of the Roadmap
Initiative, 'Re-Engineering the Clinical Research Enterprise'; RCMI
Program at Howard University, Division of Research Infrastructure,
National Center for Research Resources, NIH [NCRR-G12 RR003048]; Howard
University Cancer Center/Johns Hopkins Cancer Center Partnership,
National Cancer Institute [NCI-U54 CA091431]
FX This project has been funded in whole or in part with Federal funds from
the National Center for Research Resources (NCRR-UL1RR031975), National
Institutes of Health, through the Clinical and Translational Science
Awards Program (CTSA), a trademark of DHHS, part of the Roadmap
Initiative, 'Re-Engineering the Clinical Research Enterprise'; from the
RCMI Program at Howard University, Division of Research Infrastructure,
National Center for Research Resources, NIH (NCRR-G12 RR003048) and the
Howard University Cancer Center/Johns Hopkins Cancer Center Partnership,
National Cancer Institute, (NCI-U54 CA091431).
NR 36
TC 9
Z9 12
U1 1
U2 13
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0021-9746
EI 1472-4146
J9 J CLIN PATHOL
JI J. Clin. Pathol.
PD FEB
PY 2014
VL 67
IS 2
BP 153
EP 160
DI 10.1136/jclinpath-2013-201698
PG 8
WC Pathology
SC Pathology
GA 295HW
UT WOS:000330108200009
PM 23986556
ER
PT J
AU Lambert, LM
Pike, NA
Medoff-Cooper, B
Zak, V
Pemberton, VL
Young-Borkowski, L
Clabby, ML
Nelson, KN
Ohye, RG
Trainor, B
Uzark, K
Rudd, N
Bannister, L
Korsin, R
Cooper, DS
Pizarro, C
Zyblewski, SC
Bartle, BH
Williams, RV
AF Lambert, Linda M.
Pike, Nancy A.
Medoff-Cooper, Barbara
Zak, Victor
Pemberton, Victoria L.
Young-Borkowski, Lisa
Clabby, Martha L.
Nelson, Kathryn N.
Ohye, Richard G.
Trainor, Bethany
Uzark, Karen
Rudd, Nancy
Bannister, Louise
Korsin, Rosalind
Cooper, David S.
Pizarro, Christian
Zyblewski, Sinai C.
Bartle, Bronwyn H.
Williams, Richard V.
CA Pediat Heart Network Investigators
TI Variation in Feeding Practices following the Norwood Procedure
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID LEFT-HEART SYNDROME; SINGLE-VENTRICLE PHYSIOLOGY; LARYNGOPHARYNGEAL
DYSFUNCTION; INTERSTAGE MORTALITY; WEIGHT-GAIN; INFANTS; GROWTH;
OPERATION; PALLIATION; SURGERY
AB Objectives To assess variation in feeding practice at hospital discharge after the Norwood procedure, factors associated with tube feeding, and associations among site, feeding mode, and growth before stage II.
Study design From May 2005 to July 2008, 555 subjects from 15 centers were enrolled in the Pediatric Heart Network Single Ventricle Reconstruction Trial; 432 survivors with feeding data at hospital discharge after the Norwood procedure were analyzed.
Results Demographic and clinical variables were compared among 4 feeding modes: oral only (n = 140), oral/tube (n = 195), nasogastric tube (N-tube) only (n = 40), and gastrostomy tube (G-tube) only (n = 57). There was significant variation in feeding mode among sites (oral only 0%-81% and G-tube only 0%-56%, P < .01). After adjusting for site, multivariable modeling showed G-tube feeding at discharge was associated with longer hospitalization, and N-tube feeding was associated with greater number of discharge medications (R-2 = 0.65, P < .01). After adjusting for site, mean pre-stage II weight-for-age z-score was significantly higher in the oral-only group (-1.4) vs the N-tube-only (-2.2) and G-tube-only (-2.1) groups (P = .04 and .02, respectively).
Conclusions Feeding mode at hospital discharge after the Norwood procedure varied among sites. Prolonged hospitalization and greater number of medications at the time of discharge were associated with tube feeding. Infants exclusively fed orally had a higher weight-for-age z score pre-stage II than those fed exclusively by tube. Exploring strategies to prevent morbidities and promote oral feeding in this highest risk population is warranted.
C1 [Lambert, Linda M.] Primary Childrens Med Ctr, Salt Lake City, UT 84103 USA.
[Pike, Nancy A.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Medoff-Cooper, Barbara] Univ Penn, Sch Nursing, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Zak, Victor] New England Res Inst, Watertown, MA 02172 USA.
[Pemberton, Victoria L.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Young-Borkowski, Lisa] Med Coll Wisconsin, Childrens Hosp Wisconsin, Milwaukee, WI 53226 USA.
[Clabby, Martha L.] Emory Univ, Childrens Healthcare Atlanta, Atlanta, GA 30322 USA.
[Nelson, Kathryn N.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Ohye, Richard G.] Univ Michigan, CS Mott Childrens Hosp, Sch Med, Congenital Heart Ctr, Ann Arbor, MI 48109 USA.
[Trainor, Bethany] Boston Childrens Hosp, Boston, MA USA.
[Uzark, Karen] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA.
[Rudd, Nancy] Med Coll Wisconsin, Childrens Hosp Wisconsin, Milwaukee, WI 53226 USA.
[Bannister, Louise] Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Korsin, Rosalind] Columbia Univ, New York, NY USA.
[Cooper, David S.] Congenital Heart Inst Florida, Orlando, FL USA.
[Pizarro, Christian] Alfred I duPont Hosp Children, Wilmington, DE USA.
[Zyblewski, Sinai C.] Med Univ S Carolina, Charleston, SC 29425 USA.
[Bartle, Bronwyn H.] Duke Univ, Durham, NC USA.
[Williams, Richard V.] Univ Utah, Sch Med, Salt Lake City, UT USA.
RP Lambert, LM (reprint author), 100 N Mario Capecchi Dr,Suite 2800, Salt Lake City, UT 84113 USA.
EM Linda.lambert@imail.org
FU National Heart, Lung, and Blood Institute (NHLBI) [HL068269, HL068270,
HL068279, HL068281, HL068285, HL068292, HL068290, HL068288, HL085057,
HL109781, HL109737]
FX Supported by the National Heart, Lung, and Blood Institute (NHLBI;
HL068269, HL068270, HL068279, HL068281, HL068285, HL068292, HL068290,
HL068288, HL085057, HL109781, HL109737). Its contents are solely the
responsibility of the authors and do not necessarily represent the
official views of NHLBI or the National Institutes of Health. The
authors declare no conflicts of interest.
NR 26
TC 7
Z9 7
U1 1
U2 5
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3476
EI 1097-6833
J9 J PEDIATR-US
JI J. Pediatr.
PD FEB
PY 2014
VL 164
IS 2
BP 237
EP +
DI 10.1016/j.jpeds.2013.09.042
PG 7
WC Pediatrics
SC Pediatrics
GA 295NN
UT WOS:000330122900004
PM 24210923
ER
PT J
AU Brown, P
Gipson, C
AF Brown, Patricia
Gipson, Chester
TI A word from OLAW and USDA
SO LAB ANIMAL
LA English
DT Editorial Material
C1 [Brown, Patricia] NIH, OLAW, OER, HHS, Bethesda, MD 20892 USA.
[Gipson, Chester] USDA, APHIS, AC, Washington, DC USA.
RP Brown, P (reprint author), NIH, OLAW, OER, HHS, Bethesda, MD 20892 USA.
NR 5
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0093-7355
EI 1548-4475
J9 LAB ANIMAL
JI Lab Anim.
PD FEB
PY 2014
VL 43
IS 2
BP 55
EP 55
PG 1
WC Veterinary Sciences
SC Veterinary Sciences
GA 297MJ
UT WOS:000330259300017
PM 24451358
ER
PT J
AU Aebi, S
Gelber, S
Anderson, SJ
Lang, I
Robidoux, A
Martin, M
Nortier, JWR
Paterson, AHG
Rimawi, MF
Canada, JMB
Thurlimann, B
Murray, E
Mamounas, EP
Geyer, CE
Price, KN
Coates, AS
Gelber, RD
Rastogi, P
Wolmark, N
Wapnir, IL
AF Aebi, Stefan
Gelber, Shari
Anderson, Stewart J.
Lang, Istvan
Robidoux, Andre
Martin, Miguel
Nortier, Johan W. R.
Paterson, Alexander H. G.
Rimawi, Mothaffar F.
Canada, Jose Manuel Baena
Thuerlimann, Beat
Murray, Elizabeth
Mamounas, Eleftherios P.
Geyer, Charles E., Jr.
Price, Karen N.
Coates, Alan S.
Gelber, Richard D.
Rastogi, Priya
Wolmark, Norman
Wapnir, Irene L.
CA CALOR Investigators
TI Chemotherapy for isolated locoregional recurrence of breast cancer
(CALOR): a randomised trial
SO LANCET ONCOLOGY
LA English
DT Article
ID SURGICAL ADJUVANT BREAST; TUMOR RECURRENCE; RADIATION-THERAPY; RECEPTOR
CONVERSION; CONSERVING SURGERY; LOCAL RECURRENCE; METASTASES; PROGNOSIS;
MASTECTOMY; TAMOXIFEN
AB Background Patients with isolated locoregional recurrences (ILRR) of breast cancer have a high risk of distant metastasis and death from breast cancer. We aimed to establish whether adjuvant chemotherapy improves the outcome of such patients.
Methods The CALOR trial was a pragmatic, open-label, randomised trial that accrued patients with histologically proven and completely excised ILRR after unilateral breast cancer who had undergone a mastectomy or lumpectomy with clear surgical margins. Eligible patients were enrolled from hospitals worldwide and were centrally randomised (1: 1) to chemotherapy (type selected by the investigator; multidrug for at least four courses recommended) or no chemotherapy, using permuted blocks, and stratified by previous chemotherapy, oestrogen-receptor and progesterone-receptor status, and location of ILRR. Patients with oestrogen-receptor-positive ILRR received adjuvant endocrine therapy, radiation therapy was mandated for patients with microscopically involved surgical margins, and anti-HER2 therapy was optional. The primary endpoint was disease-free survival. All analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00074152.
Findings From Aug 22, 2003, to Jan 31, 2010, 85 patients were randomly assigned to receive chemotherapy and 77 were assigned to no chemotherapy. At a median follow-up of 4.9 years (IQR 3.6-6.0), 24 (28%) patients had disease-free survival events in the chemotherapy group compared with 34 (44%) in the no chemotherapy group. 5-year disease-free survival was 69% (95% CI 56-79) with chemotherapy versus 57% (44-67) without chemotherapy (hazard ratio 0.59 [95% CI 0.35-0.99]; p=0.046). Adjuvant chemotherapy was significantly more effective for women with oestrogen-receptor-negative ILRR (p(interaction)=0.046), but analyses of disease-free survival according to the oestrogen-receptor status of the primary tumour were not statistically significant (p(interaction)=0.43). Of the 81 patients who received chemotherapy, 12 (15%) had serious adverse events. The most common adverse events were neutropenia, febrile neutropenia, and intestinal infection.
Interpretation Adjuvant chemotherapy should be recommended for patients with completely resected ILRR of breast cancer, especially if the recurrence is oestrogen-receptor negative.
C1 [Aebi, Stefan] Luzerner Kantonsspital, CH-6000 Paris 16, France.
[Aebi, Stefan] Univ Bern, Bern, Switzerland.
[Aebi, Stefan; Thuerlimann, Beat] Swiss Grp Clin Canc Res SAKK, Bern, Switzerland.
[Gelber, Shari; Price, Karen N.; Gelber, Richard D.] Dana Farber Canc Inst, Int Breast Canc Study Grp Stat Ctr, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Gelber, Shari; Price, Karen N.; Gelber, Richard D.] Frontier Sci & Technol Res Fdn Inc, Boston, MA USA.
[Anderson, Stewart J.] Univ Pittsburgh, Dept Biostat, Natl Surg Adjuvant Breast & Bowel Project, Biostat Ctr,Dept Biostat,Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA.
[Rastogi, Priya] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
[Lang, Istvan] Natl Inst Oncol, Budapest, Hungary.
[Robidoux, Andre] Ctr Hosp Univ Montreal, Montreal, PQ, Canada.
[Martin, Miguel] Univ Complutense, Inst Invest Sanitaria Gregorio Maranon, E-28040 Madrid, Spain.
[Nortier, Johan W. R.] Leids Univ, Ctr Med, Leiden, Netherlands.
[Paterson, Alexander H. G.] Tom Baker Canc Clin, Calgary, AB, Canada.
[Rimawi, Mothaffar F.] Baylor Coll Med, Houston, TX 77030 USA.
[Canada, Jose Manuel Baena] Hosp Puerta Del Mar, Cadiz, Spain.
[Thuerlimann, Beat] Kantonsspital, Breast Ctr, St Gallen, Switzerland.
[Murray, Elizabeth] Univ Cape Town, Groote Schuur Hosp, ZA-7925 Cape Town, South Africa.
[Mamounas, Eleftherios P.] MD Anderson Canc Ctr, Orlando, FL USA.
[Geyer, Charles E., Jr.] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA USA.
[Coates, Alan S.] Int Breast Canc Study Grp, Bern, Switzerland.
[Coates, Alan S.] Univ Sydney, Sydney, NSW 2006, Australia.
[Wolmark, Norman] Allegheny Gen Hosp, Allegheny Canc Ctr, Pittsburgh, PA 15212 USA.
[Wapnir, Irene L.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
RP Aebi, S (reprint author), Luzerner Kantonsspital, CH-6000 Paris 16, France.
EM stefan.aebi@onkologie.ch
RI Aebi, Stefan/F-2004-2010;
OI Aebi, Stefan/0000-0002-3383-9449; MARTIN, MIGUEL/0000-0001-9237-3231;
Anderson, Stewart/0000-0001-8948-0650
FU US Department of Health and Human Services [U10-CA-37377, U10-CA-69974,
U10-CA-12027, U10-CA-69651, U10-CA-75362]; US Department of Health and
Human Services; Swiss Group for Clinical Cancer Research (SAKK);
Frontier Science and Technology Research Foundation; Australian and New
Zealand Breast Cancer Trials Group; Swedish Cancer Society; Oncosuisse;
Cancer Association of South Africa; Foundation for Clinical Research of
Eastern Switzerland (OSKK); Grupo Espanol de Investigacion en Cancer de
Mama (GEICAM); Dutch Breast Cancer Trialists' Group (BOOG)
FX US Department of Health and Human Services, Swiss Group for Clinical
Cancer Research (SAKK), Frontier Science and Technology Research
Foundation, Australian and New Zealand Breast Cancer Trials Group,
Swedish Cancer Society, Oncosuisse, Cancer Association of South Africa,
Foundation for Clinical Research of Eastern Switzerland (OSKK), Grupo
Espanol de Investigacion en Cancer de Mama (GEICAM), and the Dutch
Breast Cancer Trialists' Group (BOOG).
NR 28
TC 45
Z9 45
U1 3
U2 15
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
EI 1474-5488
J9 LANCET ONCOL
JI Lancet Oncol.
PD FEB
PY 2014
VL 15
IS 2
BP 156
EP 163
DI 10.1016/S1470-2045(13)70589-8
PG 8
WC Oncology
SC Oncology
GA 297AY
UT WOS:000330228700028
PM 24439313
ER
PT J
AU Rajan, A
Carter, CA
Berman, A
Cao, L
Kelly, RJ
Thomas, A
Khozin, S
Chavez, AL
Bergagnini, I
Scepura, B
Szabo, E
Lee, MJ
Trepel, JB
Browne, SK
Rosen, LB
Yu, YK
Steinberg, SM
Chen, HX
Riely, GJ
Giaccone, G
AF Rajan, Arun
Carter, Corey A.
Berman, Arlene
Cao, Liang
Kelly, Ronan J.
Thomas, Anish
Khozin, Sean
Chavez, Ariel Lopez
Bergagnini, Isabella
Scepura, Barbara
Szabo, Eva
Lee, Min-Jung
Trepel, Jane B.
Browne, Sarah K.
Rosen, Lindsey B.
Yu, Yunkai
Steinberg, Seth M.
Chen, Helen X.
Riely, Gregory J.
Giaccone, Giuseppe
TI Cixutumumab for patients with recurrent or refractory advanced thymic
epithelial tumours: a multicentre, open-label, phase 2 trial
SO LANCET ONCOLOGY
LA English
DT Article
ID FACTOR-I RECEPTOR; ADVANCED THYMOMA; ONCOLOGY-GROUP; SOLID TUMORS;
INSULIN; ANTIBODY; AUTOIMMUNITY; GEMCITABINE; EXPRESSION; INHIBITOR
AB Background No standard treatment exists for refractory or relapsed advanced thymic epithelial tumours. We investigated the efficacy of cixutumumab, a fully human IgG1 monoclonal antibody targeting the insulin-like growth factor 1 receptor in thymic epithelial tumours after failure of previous chemotherapy.
Methods Between Aug 25, 2009, and March 27, 2012, we did a multicentre, open-label, phase 2 trial in patients aged 18 years or older with histologically confirmed recurrent or refractory thymic epithelial tumours. We enrolled individuals who had progressed after at least one previous regimen of platinum-containing chemotherapy, had an Eastern Cooperative Oncology Group performance status of 0 or 1, and had measurable disease and adequate organ function. Eligible patients received intravenous cixutumumab (20 mg/kg) every 3 weeks until disease progression or development of intolerable toxic effects. The primary endpoint was the frequency of response, analysed on an intention-to-treat basis. We also did pharmacodynamic studies. This trial is registered with ClinicalTrials.gov, number NCT00965250.
Findings 49 patients were enrolled (37 with thymomas and 12 with thymic carcinomas) who received a median of eight cycles of cixutumumab (range 1-46). At the final actuarial analysis when follow-up data were updated (Nov 30, 2012), median potential follow-up (from on-study date to most current follow-up date) was 24.0 months (IQR 17.3-36.9). In the thymoma cohort, five (14%) of 37 patients (95% CI 5-29) achieved a partial response, 28 had stable disease, and four had progressive disease. In the thymic carcinoma cohort, none of 12 patients (95% CI 0-26) had a partial response, five had stable disease, and seven had progressive disease. The most common grade 3-4 adverse events in both cohorts combined were hyperglycaemia (five [10%]), lipase elevation (three [6%]), and weight loss, tumour pain, and hyperuricaemia (two each [4%]). Nine (24%) of 37 patients with thymoma developed autoimmune conditions during treatment (five were new-onset disorders), the most common of which was pure red-cell aplasia. Two (4%) patients died; one was attributed to disease progression and the other to disease-related complications (respiratory failure, myositis, and an acute coronary event), which could have been precipitated by treatment with cixutumumab.
Interpretation Cixutumumab monotherapy is well-tolerated and active in relapsed thymoma. Development of autoimmunity during treatment needs further investigation.
C1 [Rajan, Arun; Carter, Corey A.; Berman, Arlene; Kelly, Ronan J.; Thomas, Anish; Khozin, Sean; Chavez, Ariel Lopez; Scepura, Barbara; Szabo, Eva; Lee, Min-Jung; Trepel, Jane B.; Chen, Helen X.; Giaccone, Giuseppe] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Cao, Liang; Yu, Yunkai] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA.
[Bergagnini, Isabella; Riely, Gregory J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Browne, Sarah K.; Rosen, Lindsey B.] NIAID, NIH, Bethesda, MD 20892 USA.
[Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Off Clin Director, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
RP Giaccone, G (reprint author), Georgetown Univ, Washington, DC 20007 USA.
EM gg496@Georgetown.edu
RI Giaccone, Giuseppe/E-8297-2017;
OI Giaccone, Giuseppe/0000-0002-5023-7562; Thomas,
Anish/0000-0003-3293-3115
FU Division of Cancer Treatment and Diagnosis at the National Cancer
Institute (National Institutes of Health); ImClone Systems
FX Funding Division of Cancer Treatment and Diagnosis at the National
Cancer Institute (National Institutes of Health), ImClone Systems.
NR 30
TC 41
Z9 42
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
EI 1474-5488
J9 LANCET ONCOL
JI Lancet Oncol.
PD FEB
PY 2014
VL 15
IS 2
BP 191
EP 200
DI 10.1016/S1470-2045(13)70596-5
PG 10
WC Oncology
SC Oncology
GA 297AY
UT WOS:000330228700032
PM 24439931
ER
PT J
AU Chattopadhyay, PK
Gierahn, TM
Roederer, M
Love, JC
AF Chattopadhyay, Pratip K.
Gierahn, Todd M.
Roederer, Mario
Love, J. Christopher
TI Single-cell technologies for monitoring immune systems
SO NATURE IMMUNOLOGY
LA English
DT Review
ID NATURAL-KILLER-CELLS; HUMAN T-CELLS; FLOW-CYTOMETRY; MIGRATION BEHAVIOR;
GENE-EXPRESSION; MASS CYTOMETRY; CANCER-CELLS; B-CELLS; ACTIVATION;
ANTIBODIES
AB The complex heterogeneity of cells, and their interconnectedness with each other, are major challenges to identifying clinically relevant measurements that reflect the state and capability of the immune system. Highly multiplexed, single-cell technologies may be critical for identifying correlates of disease or immunological interventions as well as for elucidating the underlying mechanisms of immunity. Here we review limitations of bulk measurements and explore advances in single-cell technologies that overcome these problems by expanding the depth and breadth of functional and phenotypic analysis in space and time. The geometric increases in complexity of data make formidable hurdles for exploring, analyzing and presenting results. We summarize recent approaches to making such computations tractable and discuss challenges for integrating heterogeneous data obtained using these single-cell technologies.
C1 [Chattopadhyay, Pratip K.; Roederer, Mario] NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Gierahn, Todd M.; Love, J. Christopher] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
RP Love, JC (reprint author), MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM clove@mit.edu
OI Chattopadhyay, Pratip/0000-0002-5457-9666
FU W.M. Keck Foundation; US National Institute of Allergy And Infectious
Diseases [1U19AI089992, 1R56AI104274, 5R21AI106025]
FX This work was supported by the W.M. Keck Foundation and the US National
Institute of Allergy And Infectious Diseases (1U19AI089992, 1R56AI104274
and 5R21AI106025). The content is solely the responsibility of the
authors and does not necessarily represent the official views of the US
National Institute of Allergy And Infectious Diseases or the US National
Institutes of Health. We thank A. Shalek for helpful comments on
scRNA-seq and N. Aghaeepour for discussions about data-analysis tools.
J.C.L. is a Camille Dreyfus Teacher-Scholar. We acknowledge the service
to the MIT community of the late Sean Collier.
NR 63
TC 91
Z9 92
U1 14
U2 91
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
EI 1529-2916
J9 NAT IMMUNOL
JI Nat. Immunol.
PD FEB
PY 2014
VL 15
IS 2
BP 128
EP 135
DI 10.1038/ni.2796
PG 8
WC Immunology
SC Immunology
GA 295XV
UT WOS:000330150600004
PM 24448570
ER
PT J
AU Stratakis, CA
AF Stratakis, Constantine A.
TI ADRENAL CANCER IN 2013 Time to individualize treatment for
adrenocortical cancer?
SO NATURE REVIEWS ENDOCRINOLOGY
LA English
DT Editorial Material
AB 2013 was a good year for adrenocortical cancer, as the new knowledge gained holds great promise for patients. Advances were made in genetics, epigenetics, the advent of related technological and bioinformatic tools, and the feasibility of massive screening of people and samples.
C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NICHD, East Labs, SEGEN PDEGEN,NIH, Bethesda, MD 20892 USA.
RP Stratakis, CA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NICHD, East Labs, SEGEN PDEGEN,NIH, CRC Room 1-3330,Bldg 10-CRC,10 Ctr Dr, Bethesda, MD 20892 USA.
EM stratakc@mail.nih.gov
FU Intramural NIH HHS
NR 10
TC 7
Z9 8
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-5029
EI 1759-5037
J9 NAT REV ENDOCRINOL
JI Nat. Rev. Endocrinol.
PD FEB
PY 2014
VL 10
IS 2
BP 76
EP 78
DI 10.1038/nrendo.2013.263
PG 4
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 296LT
UT WOS:000330187200006
PM 24393782
ER
PT J
AU Prinz, WA
AF Prinz, William A.
TI THE LIPID TRADE
SO NATURE REVIEWS MOLECULAR CELL BIOLOGY
LA English
DT Editorial Material
C1 [Prinz, William A.] NIH, Bethesda, MD 20892 USA.
[Prinz, William A.] NIDDK, Lab Cell & Mol Biol, Bethesda, MD 20892 USA.
RP Prinz, WA (reprint author), NIH, 8 Ctr Dr, Bethesda, MD 20892 USA.
EM wp53m@nih.gov
NR 4
TC 6
Z9 6
U1 1
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1471-0072
EI 1471-0080
J9 NAT REV MOL CELL BIO
JI Nat. Rev. Mol. Cell Biol.
PD FEB
PY 2014
VL 15
IS 2
BP 79
EP 79
DI 10.1038/nrm3740
PG 1
WC Cell Biology
SC Cell Biology
GA 296MV
UT WOS:000330190100006
PM 24434885
ER
PT J
AU Graeff-Martins, AS
Hoven, CW
Wu, P
Bin, F
Duarte, CS
AF Graeff-Martins, Ana Soledade
Hoven, Christina W.
Wu, Ping
Bin, Fan
Duarte, Cristiane S.
TI Use of Mental Health Services by Children and Adolescents Six Months
After the World Trade Center Attack
SO PSYCHIATRIC SERVICES
LA English
DT Article
ID NEW-YORK-CITY; COUNSELING-SERVICES; PROJECT-LIBERTY; SEPTEMBER-11;
AFTERMATH; DISORDERS; PATTERNS; SCHOOL
AB Objective: The authors describe use of mental health services among children and adolescents after the September 11, 2001, attack on the World Trade Center. Methods: Six months after the attack, sixth-through 12th-graders (N=6,986) who were representative of the student population were asked about their use of mental health services to talk about the attack as well as their exposure to the attack, symptoms of posttraumatic stress and major depressive disorders, and any conversations about the attack with a parent, teacher, or religious leader. Results: Eighteen percent had used mental health services. Using in-school services was associated with conversation with a teacher about the attack. Using services outside school was associated with direct exposure to the attack, previous trauma exposure, probable psychiatric diagnosis, and conversation with a teacher or religious leader about the attack. Conclusions: Teachers and religious leaders can function as gatekeepers to identify children in need following a disaster.
C1 [Graeff-Martins, Ana Soledade] Univ Sao Paulo, Dept Psychiat, Sao Paulo, Brazil.
[Hoven, Christina W.; Bin, Fan; Duarte, Cristiane S.] Columbia Univ, Dept Child & Adolescent Psychiat, New York, NY USA.
[Hoven, Christina W.; Bin, Fan; Duarte, Cristiane S.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
[Wu, Ping] NIH, Ctr Sci Review, Bethesda, MD 20892 USA.
RP Graeff-Martins, AS (reprint author), Univ Sao Paulo, Dept Psychiat, Sao Paulo, Brazil.
EM anasoledade10@terra.com.br
RI Graeff-Martins, Ana Soledade/K-1974-2012;
OI Hoven, Christina/0000-0003-1274-2936
FU U.S. Department of Education; CNPq-Brazil [141438/2006-1]; CAPES-Brazil
[BEX3777/07-3]
FX The study was funded by the U.S. Department of Education. Dr.
Graeff-Martins received support from grant 141438/2006-1 from
CNPq-Brazil and BEX3777/07-3 from CAPES-Brazil. 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 U.S. government.
NR 15
TC 0
Z9 0
U1 0
U2 6
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 1075-2730
EI 1557-9700
J9 PSYCHIAT SERV
JI Psychiatr. Serv.
PD FEB
PY 2014
VL 65
IS 2
BP 263
EP 265
DI 10.1176/appi.ps.201200586
PG 3
WC Health Policy & Services; Public, Environmental & Occupational Health;
Psychiatry
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Psychiatry
GA 297LR
UT WOS:000330257400023
PM 24492905
ER
PT J
AU Kuranov, AB
Kozhamkulov, UA
Vavilov, MN
Belova, ES
Bismilda, VL
Alenova, AH
Ismailov, SS
Momynaliev, KT
AF Kuranov, A. B.
Kozhamkulov, U. A.
Vavilov, M. N.
Belova, E. S.
Bismilda, V. L.
Alenova, A. H.
Ismailov, S. S.
Momynaliev, K. T.
TI HLA-class II alleles in patients with drug-resistant pulmonary
tuberculosis in Kazakhstan
SO TISSUE ANTIGENS
LA English
DT Article
DE human leukocyte antigen; Kazakhstan; tuberculosis
ID OLIGONUCLEOTIDE HYBRIDIZATION; DISEASE SEVERITY; SUSCEPTIBILITY;
ASSOCIATION; FREQUENCIES; SEQUENCE; DONORS; GENES; DQA1; DRB
AB The human leukocyte antigen (HLA) system has a major role in the regulation of the immune response as it is involved in the defense against pathogens. Some studies have reported that HLA class II genes play a strong role in severe cases of pulmonary tuberculosis (PTB) in several populations. Thus the aim of the study was to compare the HLA-class II alleles of patients with drug resistant tuberculosis with those of healthy controls from the same ethnic group in Kazakhstan. The aim of the present study was to evaluate the correlation of HLA-class II alleles by patients with drug resistant tuberculosis and the healthy controls of the same ethnic group in Kazakhstan. The HLA-class II alleles of 76 patients with tuberculosis (TB) and 157 healthy volunteers were investigated using sequence-based typing (SBT)-method. HLA-DQA1*03:02 HLA-DRB1*08:01 and DRB1*08:03 occurred more frequently (P = 0.05) in patients with drug resistant tuberculosis than in controls. We observed a possible association between certain HLA alleles and TB that are specific for the Kazakh population. Further studies are needed to confirm our findings using a larger number of patients with drug resistant tuberculosis.
C1 [Kuranov, A. B.; Kozhamkulov, U. A.; Momynaliev, K. T.] Natl Biotechnol Ctr, Astana, Kazakhstan.
[Vavilov, M. N.] Chelyabinsk State Univ, Chelyabinsk, Russia.
[Belova, E. S.; Bismilda, V. L.; Alenova, A. H.; Ismailov, S. S.] Natl Ctr TB Problems, Alma Ata, Kazakhstan.
RP Kuranov, AB (reprint author), Natl Biotechnol Ctr, Astana, Kazakhstan.
EM iskander.kuranov@gmail.com
RI Kozhamkulov, Ulan/H-6805-2016
FU Ministry of Education and Science of the Republic of Kazakhstan
[N01.04.01]
FX This research was supported by funding from the Ministry of Education
and Science of the Republic of Kazakhstan N01.04.01. The authors
gratefully thank Prof. Dr Claudia A. Muller (University of Tubingen,
Tubingen, Germany) for help during the writing.
NR 28
TC 10
Z9 13
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0001-2815
EI 1399-0039
J9 TISSUE ANTIGENS
JI Tissue Antigens
PD FEB
PY 2014
VL 83
IS 2
BP 106
EP 112
DI 10.1111/tan.12279
PG 7
WC Cell Biology; Immunology; Pathology
SC Cell Biology; Immunology; Pathology
GA 292UC
UT WOS:000329927000006
PM 24397488
ER
PT J
AU Jarow, JP
Lerner, SP
Kluetz, PG
Liu, K
Sridhara, R
Bajorin, D
Chang, S
Dinney, CPN
Groshen, S
Morton, RA
O'Donnell, M
Quale, DZ
Schoenberg, M
Seigne, J
Vikram, B
AF Jarow, Jonathan P.
Lerner, Seth P.
Kluetz, Paul G.
Liu, Ke
Sridhara, Rajeshwari
Bajorin, Dean
Chang, Sam
Dinney, Colin P. N.
Groshen, Susan
Morton, Ronald A.
O'Donnell, Michael
Quale, Diane Zipursky
Schoenberg, Mark
Seigne, John
Vikram, Bhadrasain
TI Clinical Trial Design for the Development of New Therapies for
Nonmuscle-invasive Bladder Cancer: Report of a Food and Drug
Administration and American Urological Association Public Workshop
SO UROLOGY
LA English
DT Article
ID CARCINOMA IN-SITU; HEXAMINOLEVULINATE FLUORESCENCE CYSTOSCOPY; GUERIN
PLUS INTERFERON; WHITE-LIGHT CYSTOSCOPY; INTRAVESICAL THERAPY;
UROTHELIAL CARCINOMA; PHASE-III; MULTICENTER; CYSTECTOMY; RECURRENCE
AB OBJECTIVE To summarize the discussion at a public workshop, cosponsored by the U.S. Food and Drug Administration (FDA) and the American Urological Association, reviewing potential trial designs for the development of new therapies for non-muscle-invasive bladder cancer (NMIBC). There have been only 3 drug approvals for NMIBC in the last 30 years, and product development for this disease has been stymied by difficulties in trial design and patient accrual.
METHODS A workshop evaluating potential trial design for the development of therapies for NMIBC was held in San Diego, CA, in May 2013. Invited experts representing all stakeholders, including urology, medical oncology, radiation oncology, industry, and patient advocates, discussed development of products for all risk strata of NMIBC.
RESULTS The panel responded to specific questions from the FDA, discussing eligibility criteria, efficacy endpoints, and trial design for patients with a mix of high-grade papillary disease and carcinoma in situ, Bacillus Calmette-Guerin (BCG)-refractory disease, and intermediate-risk disease. Panel members also addressed the magnitude of response that would be clinically meaningful for various disease strata and trial design options for perioperative intravesical chemotherapy instillation at the time of resection of bladder tumors.
CONCLUSION Expert commentary provided by panel members will inform a planned FDA guidance on pathways for drug and biologic development for NMIBC and will be discussed at meetings of the FDA's Oncologic Drugs Advisory Committee. FDA intends to develop a set of principles that can be used to promote the development of new products for this disease. Published by Elsevier Inc.
C1 [Jarow, Jonathan P.] US FDA, Off Hematol & Oncol Prod, Silver Spring, MD 20993 USA.
Baylor Coll Med, Scott Dept Urol, Med Ctr, Houston, TX 77030 USA.
US FDA, Off Cellular Tissue & Gene Therapies, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA.
US FDA, Div Biometr 5, Off Biostat, CDER, Silver Spring, MD 20993 USA.
Weill Cornell Med Coll, Mem Sloan Kettering Canc Ctr, New York, NY USA.
Vanderbilt Univ, Med Ctr, Dept Urol Surg, Nashville, TN USA.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
USC Keck Sch Med, USC Norris Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA USA.
Amer Med Syst, Minnetonka, MN USA.
Univ Iowa, Iowa City, IA USA.
Bladder Canc Advocacy Network, Bethesda, MD USA.
Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA.
Norris Cotton Canc Ctr, Lebanon, NH USA.
NCI, Bethesda, MD 20892 USA.
RP Jarow, JP (reprint author), US FDA, Off Hematol & Oncol Prod, Silver Spring, MD 20993 USA.
EM Jonathan.jarow@fda.hhs.gov
FU NCI NIH HHS [P30 CA016672]
NR 14
TC 8
Z9 8
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0090-4295
EI 1527-9995
J9 UROLOGY
JI Urology
PD FEB
PY 2014
VL 83
IS 2
BP 262
EP 264
DI 10.1016/j.urology.2013.10.030
PG 3
WC Urology & Nephrology
SC Urology & Nephrology
GA 296ZF
UT WOS:000330223600002
PM 24332121
ER
PT J
AU Xu, F
Pang, LJ
Cai, XY
Liu, XW
Yuan, S
Fan, XQ
Jiang, B
Zhang, XW
Dou, YL
Gorospe, M
Wang, WG
AF Xu, Fang
Pang, Lijun
Cai, Xiaoyu
Liu, Xinwen
Yuan, Shuai
Fan, Xiuqin
Jiang, Bin
Zhang, Xiaowei
Dou, Yali
Gorospe, Myriam
Wang, Wengong
TI let-7-repressesed Shc translation delays replicative senescence
SO AGING CELL
LA English
DT Article
DE cellular lifespan; let-7a; p66Shc; replicative senescence; translational
regulation
ID HUMAN-DIPLOID FIBROBLASTS; P16(INK4) MESSENGER-RNA; OXIDATIVE STRESS;
LIFE-SPAN; SIGNALING PATHWAY; LONGEVITY GENE; CANCER CELLS; MICRORNA;
P66(SHC); EXPRESSION
AB The p66Shc adaptor protein is an important regulator of lifespan in mammals, but the mechanisms responsible are still unclear. Here, we show that expression of p66Shc, p52Shc, and p46Shc is regulated at the post-transcriptional level by the microRNA let-7a. The levels of let-7a correlated inversely with the levels of Shc proteins without affecting Shc mRNA levels. We identified seedless' let-7a interaction elements in the coding region of Shc mRNA; mutation of the seedless' interaction sites abolished the regulation of Shc by let-7a. Our results further revealed that repression of Shc expression by let-7a delays senescence of human diploid fibroblasts (HDFs). In sum, our findings link let-7a abundance to the expression of p66Shc, which in turn controls the replicative lifespan of HDFs.
C1 [Xu, Fang; Pang, Lijun; Cai, Xiaoyu; Liu, Xinwen; Yuan, Shuai; Fan, Xiuqin; Jiang, Bin; Zhang, Xiaowei; Wang, Wengong] Peking Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Beijing 100191, Peoples R China.
[Dou, Yali] Univ Michigan, Dept Pathol & Biol Chem, Ann Arbor, MI 48105 USA.
[Gorospe, Myriam] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA.
RP Wang, WG (reprint author), Peking Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, 38 Xueyuan Rd, Beijing 100191, Peoples R China.
EM wwg@bjmu.edu.cn
FU National Science Foundation of China [8123008, 81070247, 30921062,
30973147]; (111 project) from the Ministry of Education of People's
Republic of China [B07001]; National Institute on Aging-IRP, National
Institutes of Health
FX This study was supported by Grants 8123008, 81070247, 30921062, and
30973147 from the National Science Foundation of China; Grant B07001
(111 project) from the Ministry of Education of People's Republic of
China. MG was supported by the National Institute on Aging-IRP, National
Institutes of Health. We thank J. Shay for generously providing us the
IDH4 cells.
NR 31
TC 4
Z9 5
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1474-9718
EI 1474-9726
J9 AGING CELL
JI Aging Cell
PD FEB
PY 2014
VL 13
IS 1
BP 185
EP 192
DI 10.1111/acel.12176
PG 8
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA 290LY
UT WOS:000329760600020
PM 24165399
ER
PT J
AU Mercken, EM
Hu, J
Krzysik-Walker, S
Wei, M
Li, Y
McBurney, MW
de Cabo, R
Longo, VD
AF Mercken, Evi M.
Hu, Jia
Krzysik-Walker, Susan
Wei, Min
Li, Ying
McBurney, Michael W.
de Cabo, Rafael
Longo, Valter D.
TI SIRT1 but not its increased expression is essential for lifespan
extension in caloric-restricted mice
SO AGING CELL
LA English
DT Article
DE anti-aging; caloric restriction; lifespan; SIRT1
ID PROTECTS
AB The SIRT1 deacetylase is one of the best-studied putative mediators of some of the anti-aging effects of calorie restriction (CR), but its role in CR-dependent lifespan extension has not been demonstrated. We previously found that mice lacking both copies of SIRT1 displayed a shorter median lifespan than wild-type mice on an ad libitum diet. Here, we report that median lifespan extension in CR heterozygote SIRT1(+/-) mice was identical (51%) to that observed in wild-type mice, but SIRT1(+/-) mice displayed a higher frequency of certain pathologies. Although larger studies in additional genetic backgrounds are needed, these results provide strong initial evidence for the requirement of SIRT1 for the lifespan extension effects of CR, but suggest that its high expression is not required for CR-induced lifespan extension.
C1 [Mercken, Evi M.; de Cabo, Rafael] NIA, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA.
[Hu, Jia; Wei, Min; Li, Ying; Longo, Valter D.] Univ So Calif, Davis Sch Gerontol, Los Angeles, CA 90089 USA.
[Hu, Jia; Wei, Min; Li, Ying; Longo, Valter D.] Univ So Calif, Dept Biol Sci, Los Angeles, CA 90089 USA.
[Krzysik-Walker, Susan] NIA, Lab Clin Invest, NIH, Baltimore, MD 21224 USA.
[McBurney, Michael W.] Univ Ottawa, Ottawa Hosp Res Inst, Dept Med, Ottawa, ON K1H 8L6, Canada.
RP Longo, VD (reprint author), Univ So Calif, Davis Sch Gerontol, Los Angeles, CA 90089 USA.
EM decabora@grc.nia.nih.gov; vlongo@usc.edu
RI de Cabo, Rafael/J-5230-2016;
OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693; Wei,
Min/0000-0002-2649-9271
FU NIH/NIA [AG20642, AG025135, AG034906]; Intramural Research Program of
the NIA/NIH
FX This study was funded, in part, by NIH/NIA grants AG20642, AG025135, and
AG034906 and by the Intramural Research Program of the NIA/NIH. Data
have been deposited at the Gene Expression Omnibus
(http://www.ncbi.nlm.nih.gov/geo/) under accession code GSE46895.
NR 14
TC 32
Z9 32
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1474-9718
EI 1474-9726
J9 AGING CELL
JI Aging Cell
PD FEB
PY 2014
VL 13
IS 1
BP 193
EP 196
DI 10.1111/acel.12151
PG 4
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA 290LY
UT WOS:000329760600021
PM 23941528
ER
PT J
AU Miskulin, DC
Abebe, KZ
Chapman, AB
Perrone, RD
Steinman, TI
Torres, VE
Bae, KT
Braun, W
Winklhofer, FT
Hogan, MC
Rahbari-Oskoui, F
Moore, CG
Flessner, MF
Schrier, RW
AF Miskulin, Dana C.
Abebe, Kaleab Z.
Chapman, Arlene B.
Perrone, Ronald D.
Steinman, Theodore I.
Torres, Vicente E.
Bae, K. Ty
Braun, William
Winklhofer, Franz T.
Hogan, Marie C.
Rahbari-Oskoui, Fred
Moore, Charity G.
Flessner, Michael F.
Schrier, Robert W.
CA HALT-PKD Study
TI Health-Related Quality of Life in Patients With Autosomal Dominant
Polycystic Kidney Disease and CKD Stages 1-4: A Cross-sectional Study
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Article
DE Autosomal dominant polycystic kidney disease (ADPKD); quality of life
(QoL); chronic kidney disease (CKD); patient-reported outcomes;
extrarenal symptoms; renal disease; activities of daily life
ID VOLUME PROGRESSION; RENAL-FUNCTION; LIVER-DISEASE; PAIN; CYST; OUTCOMES;
GROWTH
AB Background: In people with early autosomal dominant polycystic kidney disease (ADPKD), average total kidney volume (TKV) is 3 times normal and increases by an average of 5% per year despite a seemingly normal glomerular filtration rate (GFR). We hypothesized that increased TKV would be a source of morbidity and diminished quality of life that would be worse in patients with more advanced disease.
Study Design: Cross-sectional.
Setting & Participants: 1,043 patients with ADPKD, hypertension, and a baseline estimated GFR (eGFR) > 20 mL/min/1.73 m(2).
Predictors: (1) eGFR, (2) height-adjusted TKV (htTKV) in patients with eGFR > 60 mL/min/1.73 m(2).
Outcomes: 36-Item Short Form Health Survey (SF-36) and the Wisconsin Brief Pain Survey.
Measurements: Questionnaires were self-administered. GFR was estimated from serum creatinine using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation. htTKV was measured by magnetic resonance imaging.
Results: Back pain was reported by 50% of patients, and 20% experienced it "often, usually, or always." In patients with early disease (eGFR > 60 mL/min/1.73 m(2)), there was no association between pain and htTKV, except in patients with large kidneys (htTKV > 1,000 mL/m). Comparing across eGFR levels and including patients with eGFRs < 60 mL/min/1.73 m(2), patients with eGFRs of 20-44 mL/min/1.73 m(2) were significantly more likely to report that pain impacted on their daily lives and had lower SF-36 scores than patients with eGFRs of 45-60 and >= 60 mL/min/1.73 m(2). Symptoms relating to abdominal fullness were reported by 20% of patients and were related significantly to lower eGFRs in women, but not men.
Limitations: TKV and liver volume were not measured in patients with eGFR < 60 mL/min/1.73 m(2). The number of patients with eGFRs < 30 mL/min/1.73 m(2) is small. Causal inferences are limited by cross-sectional design.
Conclusions: Pain is a common early symptom in the course of ADPKD, although it is not related to kidney size in early disease (eGFR > 60 mL/min/1.73 m(2)), except in individuals with large kidneys (htTKV > 1,000 mL/m). Symptoms relating to abdominal fullness and pain are greater in patients with more advanced (eGFR, 20-45 mL/min/1.73 m(2)) disease and may be due to organ enlargement, especially in women. More research about the role of TKV in quality of life and outcomes of patients with ADPKD is warranted. (C) 2014 by the National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
C1 [Miskulin, Dana C.; Perrone, Ronald D.] Tufts Med Ctr, Boston, MA USA.
[Abebe, Kaleab Z.; Bae, K. Ty; Moore, Charity G.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
[Chapman, Arlene B.; Rahbari-Oskoui, Fred] Emory Univ, Sch Med, Atlanta, GA USA.
[Steinman, Theodore I.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Torres, Vicente E.; Hogan, Marie C.] Mayo Clin, Coll Med, Rochester, MN USA.
[Braun, William] Cleveland Clin, Cleveland, OH 44106 USA.
[Winklhofer, Franz T.] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA.
[Flessner, Michael F.] NIDDK, NIH, Bethesda, MD 20892 USA.
[Schrier, Robert W.] Univ Colorado, Hlth Sci Ctr, Denver, CO USA.
RP Miskulin, DC (reprint author), 800 Washington St,Box 391, Boston, MA 02111 USA.
EM dmiskulin@tuftsmedicalcenter.org
OI Moore, Charity/0000-0002-0060-0124; Abebe, Kaleab/0000-0002-3644-8419
FU National Institute of Diabetes and Digestive and Kidney Diseases, NIH
[DK62408, DK62401, DK62410, DK62402, DK62411]; National Center for
Research Resources General Clinical Research Center (Emory University)
[RR00585]; National Center for Research Resources General Clinical
Research Center (Mayo Clinic) [RR000054]; National Center for Research
Resources General Clinical Research Center (Tufts University)
[RR000051]; National Center for Research Resources General Clinical
Research Center (University of Colorado) [RR23940]; National Center for
Research Resources General Clinical Research Center (Kansas University);
National Center for Research Resources General Clinical Research Center
(Beth Israel Deaconess Medical Center) [RR024296]; Centers for
Translational Science Activities at the participating institution (Emory
University) [RR025008]; Centers for Translational Science Activities at
the participating institution (Mayo Clinic) [RR024150]; Centers for
Translational Science Activities at the participating institution (Tufts
University) [RR025752]; Centers for Translational Science Activities at
the participating institution (University of Colorado) [RR025780];
Centers for Translational Science Activities at the participating
institution (Cleveland Clinic) [RR024989]; Publications and
Communications Committees from the PKD Research Foundation
FX This study was supported by cooperative agreements (grants DK62408,
DK62401, DK62410, DK62402, and DK62411) with the National Institute of
Diabetes and Digestive and Kidney Diseases, NIH, the National Center for
Research Resources General Clinical Research Centers (RR000039 Emory
University, RR00585 Mayo Clinic, RR000054 Tufts University, RR000051
University of Colorado, RR23940 Kansas University, and RR024296 Beth
Israel Deaconess Medical Center), and the Centers for Translational
Science Activities at the participating institutions (RR025008 Emory
University, RR024150 Mayo Clinic, RR025752 Tufts University, RR025780
University of Colorado, and RR024989 Cleveland Clinic). Support for the
study enrollment phase was also provided by grants to the Publications
and Communications Committees from the PKD Research Foundation. Study
drugs were donated by Boehringer Ingelheim Pharmaceuticals Inc
(telmisartan and placebo) and Merck & Co Inc (lisinopril).
NR 25
TC 22
Z9 22
U1 0
U2 8
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0272-6386
EI 1523-6838
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD FEB
PY 2014
VL 63
IS 2
BP 214
EP 226
DI 10.1053/j.ajkd.2013.08.017
PG 13
WC Urology & Nephrology
SC Urology & Nephrology
GA 293NX
UT WOS:000329980100009
PM 24183837
ER
PT J
AU Yang, W
Xie, DW
Anderson, AH
Joffe, MM
Greene, T
Teal, V
Hsu, CY
Fink, JC
He, J
Lash, JP
Ojo, A
Rahman, M
Nessel, L
Kusek, JW
Feldman, HI
AF Yang, Wei
Xie, Dawei
Anderson, Amanda H.
Joffe, Marshall M.
Greene, Tom
Teal, Valerie
Hsu, Chi-Yuan
Fink, Jeffrey C.
He, Jiang
Lash, James P.
Ojo, Akinlolu
Rahman, Mahboob
Nessel, Lisa
Kusek, John W.
Feldman, Harold I.
CA CRIC Study Investigators
TI Association of Kidney Disease Outcomes With Risk Factors for CKD:
Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Article
DE Kidney disease progression; disease trajectory; longitudinal outcome;
end-stage renal disease (ESRD); estimated glomerular filtration rate
(eGFR); renal function; mortality risk; chronic kidney disease (CKD);
Chronic Renal Insufficiency Cohort (CRIC); decreased estimated
glomerular filtration rate (eGFR)
ID DIETARY-PROTEIN RESTRICTION; BASE-LINE CHARACTERISTICS; PROGRESSION;
NEPHROPATHY; DESIGN; TRIAL; GFR
AB Background: Various indicators of progression of chronic kidney disease (CKD) have been used as outcomes in clinical research studies. The effect of using varying measures on the association of risk factors with CKD progression has not been well characterized.
Study Design: Prospective cohort study.
Setting & Participants: The Chronic Renal Insufficiency Cohort (CRIC) Study (N = 3,939) enrolled men and women with mild to moderate CKD, 48% of whom had diabetes and 42% were self-reported black race.
Predictors: Age, race, sex, diabetes, baseline estimated glomerular filtration rate (eGFR), proteinuria, and other established CKD risk factors.
Outcomes: Death, end-stage renal disease (ESRD), and eGFR events, including: (1) eGFR halving, (2) eGFR, 15 mL/min/1.73 m(2), (3) eGFR halving and,15 mL/min/1.73 m(2), (4) eGFR decrease of 20 mL/min/1.73 m(2), (5) eGFR halving or decrease of 20 mL/min/1.73 m(2), and (6) eGFR decrease of 25% and change in CKD stage.
Results: Mean entry eGFR was 44.9 mL/min/1.73 m(2). Annual rates of death, ESRD, and eGFR halving were 2.5%, 4.0%, and 6.1%, respectively, during an average follow-up of 5.4 years. Associations between risk factors and ESRD and eGFR events were similar across different definitions. However, these associations were substantially different from those with death. HRs for ESRD, eGFR halving, and death in the highest compared to the lowest proteinuria category were 11.83 (95% CI, 8.40-16.65), 11.19 (95% CI, 8.53-14.68), and 1.47 (95% CI, 1.10-1.96), respectively.
Limitations: Participants may not be representative of the entire CKD population.
Conclusions: Using ESRD or eGFR events, but not death, in the definition of kidney disease outcomes is appropriate in follow-up studies to identify risk factors for CKD progression. (C) 2014 by the National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
C1 [Yang, Wei; Xie, Dawei; Anderson, Amanda H.; Joffe, Marshall M.; Teal, Valerie; Nessel, Lisa; Feldman, Harold I.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Greene, Tom] Univ Utah, Salt Lake City, UT USA.
[Hsu, Chi-Yuan] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Fink, Jeffrey C.] Univ Maryland, Baltimore, MD 21201 USA.
[He, Jiang] Tulane Univ, New Orleans, LA 70118 USA.
[Lash, James P.] Univ Illinois, Chicago, IL USA.
[Ojo, Akinlolu] Univ Michigan, Ann Arbor, MI 48109 USA.
[Rahman, Mahboob] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Kusek, John W.] NIDDK, Bethesda, MD 20892 USA.
RP Yang, W (reprint author), Univ Penn, Perelman Sch Med, 295 John Morgan Bldg,3620 Hamilton Walk, Philadelphia, PA 19104 USA.
EM weiyang@mail.med.upenn.edu
OI Fink, Jeffrey/0000-0002-5622-5052
FU National Institute of Diabetes and Digestive and Kidney Diseases
[U01DK060990, U01DK060984, U01DK061022, U01DK061021, U01DK061028,
U01DK060980, U01DK060963, U01DK060902]; Perelman School of Medicine at
the University of Pennsylvania Clinical and Translational Science Award
(National Institutes of Health [NIH]/National Center for Advancing
Translational Sciences [NCATS]) [UL1TR000003, K01DK092353]; Johns
Hopkins University [UL1 TR-000424]; University of Maryland [GCRC M01
RR-16500]; NIH/NCATS and NIH Roadmap for Medical Research [UL1TR000439];
Michigan Institute for Clinical and Health Research [UL1TR000433];
University of Illinois at Chicago Clinical and Translational Science
Award [UL1RR029879]; Tulane University Translational Research in
Hypertension and Renal Biology [P30GM103337]; Kaiser Permanente
(NIH/National Center for Research Resources University of California,
San Francisco-Clinical and Translational Science Institute grant) [UL1
RR-024131]
FX Funding for the CRIC Study was obtained under a cooperative agreement
from the National Institute of Diabetes and Digestive and Kidney
Diseases (grants U01DK060990, U01DK060984, U01DK061022, U01DK061021,
U01DK061028, U01DK060980, U01DK060963, and U01DK060902). In addition,
this work was supported in part by the Perelman School of Medicine at
the University of Pennsylvania Clinical and Translational Science Award
(National Institutes of Health [NIH]/National Center for Advancing
Translational Sciences [NCATS] grants UL1TR000003, K01DK092353), Johns
Hopkins University (grant UL1 TR-000424), University of Maryland (grant
GCRC M01 RR-16500), Clinical and Translational Science Collaborative of
Cleveland (grant UL1TR000439 from the NIH/NCATS and NIH Roadmap for
Medical Research), Michigan Institute for Clinical and Health Research
(grant UL1TR000433), University of Illinois at Chicago Clinical and
Translational Science Awards (grant UL1RR029879), Tulane University
Translational Research in Hypertension and Renal Biology (grant
P30GM103337), and Kaiser Permanente (NIH/National Center for Research
Resources University of California, San Francisco-Clinical and
Translational Science Institute grant UL1 RR-024131).
NR 15
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Z9 24
U1 0
U2 2
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0272-6386
EI 1523-6838
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD FEB
PY 2014
VL 63
IS 2
BP 236
EP 243
DI 10.1053/j.ajkd.2013.08.028
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA 293NX
UT WOS:000329980100011
PM 24182662
ER
PT J
AU Hashim, T
Elbaz, S
Patel, K
Morgan, CJ
Fonarow, GC
Fleg, JL
McGwin, G
Cutter, GR
Allman, RM
Prabhu, SD
Zile, MR
Bourge, RC
Ahmed, A
AF Hashim, Taimoor
Elbaz, Shereen
Patel, Kanan
Morgan, Charity J.
Fonarow, Gregg C.
Fleg, Jerome L.
McGwin, Gerald
Cutter, Gary R.
Allman, Richard M.
Prabhu, Sumanth D.
Zile, Michael R.
Bourge, Robert C.
Ahmed, Ali
TI Digoxin and 30-day All-cause Hospital Admission in Older Patients with
Chronic Diastolic Heart Failure
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Article
DE Diastolic heart failure; Digoxin; 30-day all-cause hospital admission
ID ANGINA-PECTORIS; MORTALITY; TRIAL; HYPERTROPHY; MORBIDITY; PROGRAM
AB BACKGROUND: In the main Digitalis Investigation Group (DIG) trial, digoxin reduced the risk of 30-day all-cause hospitalization in older systolic heart failure patients. However, this effect has not been studied in older diastolic heart failure patients.
METHODS: In the ancillary DIG trial, of the 988 patients with chronic heart failure and preserved (> 45%) ejection fraction, 631 were age >= 65 years (mean age 73 years, 45% women, 12% non-whites), of whom 311 received digoxin.
RESULTS: All-cause hospitalization 30-day post randomization occurred in 4% of patients in the placebo group and 9% each among those in the digoxin group receiving 0.125 mg and >= 0.25 mg a day dosage (P = .026). Hazard ratios (HR) and 95% confidence intervals (CI) for digoxin use overall for 30-day, 3-month, and 12-month all-cause hospitalizations were 2.46 (1.25-4.83), 1.45 (0.96-2.20) and 1.14 (0.89-1.46), respectively. There was one 30-day death in the placebo group. Digoxin-associated HRs (95% CIs) for 30-day hospitalizations due to cardiovascular, heart failure, and unstable angina causes were 2.82 (1.18-6.69), 0.51 (0.09-2.79), and 6.21 (0.75-51.62), respectively. Digoxin had no significant association with 30-day all-cause hospitalization among younger patients (6% vs 7% for placebo; HR 0.80; 95% CI, 0.36-1.79).
CONCLUSIONS: In older patients with chronic diastolic heart failure, digoxin increased the risk of 30-day all-cause hospital admission, but not during longer follow-up. Although chance finding due to small sample size is possible, these data suggest that unlike in systolic heart failure, digoxin may not reduce 30-day all-cause hospitalization in older diastolic heart failure patients. Published by Elsevier Inc.
C1 [Hashim, Taimoor; Elbaz, Shereen; Patel, Kanan; Morgan, Charity J.; McGwin, Gerald; Cutter, Gary R.; Allman, Richard M.; Prabhu, Sumanth D.; Bourge, Robert C.; Ahmed, Ali] Univ Alabama Birmingham, Birmingham, AL USA.
[Fonarow, Gregg C.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Fleg, Jerome L.] NHLBI, Bethesda, MD 20892 USA.
[Allman, Richard M.; Prabhu, Sumanth D.; Ahmed, Ali] Vet Affairs Med Ctr, Birmingham, AL USA.
[Zile, Michael R.] Med Univ S Carolina, Charleston, SC 29425 USA.
[Zile, Michael R.] Vet Affairs Med Ctr, Ralph H Johnson Dept, Charleston, SC 29403 USA.
RP Ahmed, A (reprint author), UAB Comprehens Ctr Healthy Aging, 1720 2nd Ave South,CH19-219, Birmingham, AL 35294 USA.
EM aahmed@uab.edu
FU National Heart, Lung, and Blood Institute (NHLBI); Department of
Veterans Affairs Cooperative Studies Program; National Institutes of
Health from the NHLBI [R01-HL085561, R01-HL085561-S, R01-HL097047]
FX The Digitalis Investigation Group (DIG) study was conducted and
supported by the National Heart, Lung, and Blood Institute (NHLBI) and
the Department of Veterans Affairs Cooperative Studies Program, in
collaboration with the DIG Investigators. This article was prepared
using a limited access dataset obtained from the NHLBI and does not
necessarily reflect the opinions or views of the DIG Study or the NHLBI.
Dr. Ahmed was in part supported by the National Institutes of Health
through grants (R01-HL085561, R01-HL085561-S and R01-HL097047) from the
NHLBI.
NR 15
TC 8
Z9 11
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9343
EI 1555-7162
J9 AM J MED
JI Am. J. Med.
PD FEB
PY 2014
VL 127
IS 2
BP 132
EP 139
DI 10.1016/j.amjmed.2013.08.006
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 293PQ
UT WOS:000329985800018
PM 24067296
ER
PT J
AU Klempner, MS
Baker, PJ
Shapiro, ED
Marques, A
Dattwyler, RJ
Halperin, JJ
Wormser, GP
AF Klempner, Mark S.
Baker, Phillip J.
Shapiro, Eugene D.
Marques, Adriana
Dattwyler, Raymond J.
Halperin, John J.
Wormser, Gary P.
TI Potential Benefits of Retreatment Highlight the Need for Additional Lyme
Disease Research Reply
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Letter
ID PERSISTENT SYMPTOMS; TRIALS
C1 [Klempner, Mark S.] Univ Massachusetts, Sch Med, Boston, MA 02125 USA.
[Baker, Phillip J.] Amer Lyme Dis Fdn, Lyme, CT USA.
[Shapiro, Eugene D.] Yale Univ, Dept Pediat, New Haven, CT 06520 USA.
[Shapiro, Eugene D.] Yale Univ, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA.
[Shapiro, Eugene D.] Yale Univ, Dept Invest Med, New Haven, CT USA.
[Marques, Adriana] NIAID, NIH, Bethesda, MD 20892 USA.
[Dattwyler, Raymond J.] New York Med Coll, Dept Med, Div Allergy Immunol & Rheumatol, Valhalla, NY 10595 USA.
[Halperin, John J.] Overlook Med Ctr, Dept Neurosci, Summit, NJ USA.
[Halperin, John J.] Atlantic Neurosci Inst, Summit, NJ USA.
[Wormser, Gary P.] New York Med Coll, Dept Med, Div Infect Dis, Valhalla, NY 10595 USA.
RP Klempner, MS (reprint author), Univ Massachusetts, Sch Med, Harbor Campus, Boston, MA 02125 USA.
FU NCATS NIH HHS [KL2 TR001862]
NR 12
TC 0
Z9 0
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9343
EI 1555-7162
J9 AM J MED
JI Am. J. Med.
PD FEB
PY 2014
VL 127
IS 2
BP E11
EP E12
DI 10.1016/j.amjmed.2013.09.029
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 293PQ
UT WOS:000329985800006
PM 24462014
ER
PT J
AU Holford, TR
Levy, DT
Mckay, LA
Clarke, L
Racine, B
Meza, R
Land, S
Jeon, J
Feuer, EJ
AF Holford, Theodore R.
Levy, David T.
Mckay, Lisa A.
Clarke, Lauren
Racine, Ben
Meza, Rafael
Land, Stephanie
Jeon, Jihyoun
Feuer, Eric J.
TI Patterns of Birth Cohort-Specific Smoking Histories, 1965-2009
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID POLICY SIMULATION-MODEL; TOBACCO CONTROL; UNITED-STATES;
PUBLIC-POLICIES; US POPULATION; LUNG-CANCER; PREVALENCE; MORTALITY;
PERIOD; RATES
AB Background: Characterizing the smoking patterns for different birth cohorts is essential for evaluating the impact of tobacco control interventions and predicting smoking-related mortality, but the process of estimating birth cohort smoking histories has received limited attention.
Purpose: Smoking history summaries were estimated beginning with the 1890 birth cohort in order to provide fundamental parameters that can be used in studies of cigarette smoking intervention strategies.
Methods: U.S. National Health Interview Surveys conducted from 1965 to 2009 were used to obtain cross-sectional information on current smoking behavior. Surveys that provided additional detail on history for smokers including age at initiation and cessation and smoking intensity were used to construct smoking histories for participants up to the date of survey. After incorporating survival differences by smoking status, age-period-cohort models with constrained natural splines were used to estimate the prevalence of current, former, and never smokers in cohorts beginning in 1890. This approach was then used to obtain yearly estimates of initiation, cessation, and smoking intensity for the age-specific distribution for each birth cohort. These rates were projected forward through 2050 based on recent trends.
Results: This summary of smoking history shows clear trends by gender, cohort, and age over time. If current patterns persist, a slow decline in smoking prevalence is projected from 2010 through 2040.
Conclusions: A novel method of generating smoking histories has been applied to develop smoking histories that can be used in micro-simulation models, and has been incorporated in the National Cancer Institute's Smoking History Generator. These aggregate estimates developed by age, gender, and cohort will provide a complete source of smoking data over time.
C1 [Holford, Theodore R.; Mckay, Lisa A.] Yale Univ, Sch Publ Hlth, Dept Biostat, New Haven, CT 06520 USA.
[Levy, David T.] Canc Control Dept Oncol, Washington, DC USA.
[Clarke, Lauren; Racine, Ben] Cornerstone Syst Northwest Inc, Lynden, WA USA.
[Jeon, Jihyoun] Fred Hutchinson Canc Res Ctr, Dept Biostat, Seattle, WA 98104 USA.
[Jeon, Jihyoun] Fred Hutchinson Canc Res Ctr, Dept Biomath, Seattle, WA 98104 USA.
[Meza, Rafael] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Land, Stephanie; Feuer, Eric J.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Holford, TR (reprint author), Yale Univ, Sch Publ Hlth, Dept Biostat, 60 Coll St, New Haven, CT 06520 USA.
EM theodore.holford@yale.edu
FU National Cancer Institute of the U.S. NIH [CA152956]
FX This work was supported by the National Cancer Institute of the U.S. NIH
(grant CA152956).
NR 30
TC 28
Z9 28
U1 1
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
EI 1873-2607
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD FEB
PY 2014
VL 46
IS 2
BP E31
EP E37
DI 10.1016/j.amepre.2013.10.022
PG 7
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 291VM
UT WOS:000329859200002
PM 24439359
ER
PT J
AU Li, MX
Wilson, DM
AF Li, Mengxia
Wilson, David M., III
TI Human Apurinic/Apyrimidinic Endonuclease 1
SO ANTIOXIDANTS & REDOX SIGNALING
LA English
DT Review
ID BASE-EXCISION-REPAIR; HUMAN AP-ENDONUCLEASE; APURINIC-APYRIMIDINIC
ENDONUCLEASE; AMYOTROPHIC-LATERAL-SCLEROSIS; DNA-DAMAGING AGENTS; STRAND
BREAK REPAIR; SINGLE NUCLEOTIDE POLYMORPHISMS; ENHANCES
CELLULAR-SENSITIVITY; ACID SUBSTITUTION VARIANTS; EPITHELIAL
OVARIAN-CANCER
AB Significance: Human apurinic/apyrimidinic endonuclease 1 (APE1, also known as REF-1) was isolated based on its ability to cleave at AP sites in DNA or activate the DNA binding activity of certain transcription factors. We review herein topics related to this multi-functional DNA repair and stress-response protein. Recent Advances: APE1 displays homology to Escherichia coli exonuclease III and is a member of the divalent metal-dependent / fold-containing phosphoesterase superfamily of enzymes. APE1 has acquired distinct active site and loop elements that dictate substrate selectivity, and a unique N-terminus which at minimum imparts nuclear targeting and interaction specificity. Additional activities ascribed to APE1 include 3-5 exonuclease, 3-repair diesterase, nucleotide incision repair, damaged or site-specific RNA cleavage, and multiple transcription regulatory roles. Critical Issues: APE1 is essential for mouse embryogenesis and contributes to cell viability in a genetic background-dependent manner. Haploinsufficient APE1(+/-) mice exhibit reduced survival, increased cancer formation, and cellular/tissue hyper-sensitivity to oxidative stress, supporting the notion that impaired APE1 function associates with disease susceptibility. Although abnormal APE1 expression/localization has been seen in cancer and neuropathologies, and impaired-function variants have been described, a causal link between an APE1 defect and human disease remains elusive. Future Directions: Ongoing efforts aim at delineating the biological role(s) of the different APE1 activities, as well as the regulatory mechanisms for its intra-cellular distribution and participation in diverse molecular pathways. The determination of whether APE1 defects contribute to human disease, particularly pathologies that involve oxidative stress, and whether APE1 small-molecule regulators have clinical utility, is central to future investigations.
C1 [Li, Mengxia; Wilson, David M., III] NIA, Intramural Res Program, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
RP Wilson, DM (reprint author), NIA, Intramural Res Program, Lab Mol Gerontol, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM wilsonda@mail.nih.gov
FU NIH, National Institute on Aging
FX This effort was supported by the Intramural Research Program at NIH,
National Institute on Aging. The authors thank Peter Sykora and Jennifer
Illuzzi for their critical reading of the article.
NR 249
TC 46
Z9 51
U1 3
U2 24
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1523-0864
EI 1557-7716
J9 ANTIOXID REDOX SIGN
JI Antioxid. Redox Signal.
PD FEB 1
PY 2014
VL 20
IS 4
BP 678
EP 707
DI 10.1089/ars.2013.5492
PG 30
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 292VA
UT WOS:000329929400010
PM 23834463
ER
PT J
AU Pickens, CL
Theberge, FR
AF Pickens, Charles L.
Theberge, Florence R.
TI Blockade of CB1 receptors prevents retention of extinction but does not
increase low preincubated conditioned fear in the fear incubation
procedure
SO BEHAVIOURAL PHARMACOLOGY
LA English
DT Article
DE CB1; endocannabinoids; fear conditioning; fear incubation; rimonabant
ID CANNABINOID RECEPTORS; ANTAGONIST SR141716A; EMOTIONAL RESPONSE; RATS;
ANXIETY; SUPPRESSION; MODEL; HABITUATION; ADAPTATION; MEMORIES
AB We recently developed a procedure to study fear incubation, in which rats given 100 tone-shock pairings over 10 days show low fear 2 days after conditioned fear training and high fear after 30 days. Notably, fear 2 days after 10 sessions of fear conditioning is lower than fear seen 2 days after a single session of fear conditioning, suggesting that fear is suppressed. Here, we investigate the potential role of CB1 receptor activation by endocannabinoids in this fear suppression. We subjected rats to 10 days of fear conditioning and then administered systemic injections of the CB1 receptor antagonist SR141716 before a conditioned fear test was conducted 2 days later under extinction conditions. A second test was conducted without any injections on the following day (3 days after training) to examine retention of fear extinction. SR141716 injections did not increase fear expression 2 days after extended fear conditioning or affect within-session extinction; however, it impaired retention of between-session fear extinction in the day 3 test. These data suggest that CB1 receptor activation does not suppress fear soon after extended fear conditioning in the fear incubation task. The data also add to the existing literature on the role of CB1 receptors in extinction of conditioned fear.
C1 [Pickens, Charles L.; Theberge, Florence R.] NIDA, Behav Neurosci Branch, IRP, NIH,DHHS, Baltimore, MD USA.
RP Pickens, CL (reprint author), Kansas State Univ, Dept Psychol Sci, 469 Bluemont Hall, Manhattan, KS 66506 USA.
EM pickens@ksu.edu
FU Intramural Research Program of the NIDA, NIH
FX This research was supported by the Intramural Research Program of the
NIDA, NIH. We thank Ozge Gunduz-Cinar and Yavin Shaham for helpful
comments on this manuscript.
NR 45
TC 1
Z9 1
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0955-8810
EI 1473-5849
J9 BEHAV PHARMACOL
JI Behav. Pharmacol.
PD FEB
PY 2014
VL 25
IS 1
BP 23
EP 31
DI 10.1097/FBP.0000000000000020
PG 9
WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy
SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy
GA 291YM
UT WOS:000329868800003
PM 24346290
ER
PT J
AU Okun, E
Griffioen, KJ
Rothman, S
Wan, RQ
Cong, WN
De Cabo, R
Martin-Montalvo, A
Levette, A
Maudsley, S
Martin, B
Arumugam, TV
Mattson, MP
AF Okun, Eitan
Griffioen, Kathleen J.
Rothman, Sarah
Wan, Ruiqian
Cong, Wei-Na
De Cabo, Rafael
Martin-Montalvo, Alejandro
Levette, Andrew
Maudsley, Stuart
Martin, Bronwen
Arumugam, Thiruma Valavan
Mattson, Mark P.
TI Toll-like receptors 2 and 4 modulate autonomic control of heart rate and
energy metabolism
SO BRAIN BEHAVIOR AND IMMUNITY
LA English
DT Article
DE Innate immunity; Toll-like receptors; TLR2; TLR4; Autonomic nervous
system; ANS; Heart rate; Stress
ID BROWN ADIPOSE-TISSUE; PROGENITOR-CELL PROLIFERATION; ADULT HIPPOCAMPAL
NEUROGENESIS; SYMPATHETIC-NERVOUS-SYSTEM; NEGATIVE REGULATOR;
CARDIAC-HYPERTROPHY; NEURONAL APOPTOSIS; INNATE IMMUNITY; FAILING HEART;
WHOLE-BLOOD
AB Toll-like receptors (TLR) are innate immune receptors typically activated by microbial-associated molecular patterns (MAMPs) during infection or damage-associated molecular patterns (DAMPs) as a result of tissue injury. Recent findings suggest that TLR2 and TLR4 signaling play important roles in developmental and adult neuroplasticity, and in learning and memory. In addition, activation of TLR2 and TLR4 worsens ischemic injury to the heart and brain in animal models of myocardial infarction and stroke. TLR activation is also implicated in thermoregulation and fever in response to infection. However, it is not known whether TLRs participate in the regulation of the sympathetic and/or parasympathetic components of the autonomic nervous system (ANS). Here we provide evidence that TLR2 and TLR4 influence autonomic regulation of heart rate (HR) body temperature and energy metabolism in mice. We show that mice lacking TLR2 or TLR4 exhibit reduced basal HR, which results from an increase of parasympathetic tone. In addition, thermoregulatory responses to stress are altered in TLR2-/- and TLR4-/- mice, and brown fat-dependent thermoregulation is altered in TLR4-/- mice. Moreover, TLR2-/- and TLR4-/- mice consume less food and exhibit a greater mass compared to wild type mice. Collectively, our findings suggest important roles for TLR2 and TLR4 in the ANS regulation of cardiovascular function, thermoregulation, and energy metabolism. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Okun, Eitan] Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, Leslie & Susan Gonda Multidisciplinary Brain Res, IL-52900 Ramat Gan, Israel.
[Griffioen, Kathleen J.; Rothman, Sarah; Wan, Ruiqian; Maudsley, Stuart; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
[Cong, Wei-Na; Martin, Bronwen] NIA, Clin Invest Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[De Cabo, Rafael; Martin-Montalvo, Alejandro; Levette, Andrew] NIA, Translat Gerontol Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Arumugam, Thiruma Valavan] Univ Queensland, Dept Neurol, St Lucia, Qld 4067, Australia.
[Mattson, Mark P.] Johns Hopkins Univ, Sch Med, Sch Biomed Sci, Baltimore, MD 21205 USA.
RP Okun, E (reprint author), Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, Leslie & Susan Gonda Multidisciplinary Brain Res, Bldg 901,Room 312, IL-52900 Ramat Gan, Israel.
EM eitan.okun@biu.ac.il
RI Arumugam, Thiruma/B-4898-2011; de Cabo, Rafael/J-5230-2016; okun,
eitan/K-1314-2016; Martin-Montalvo, Alejandro/C-2031-2017;
OI de Cabo, Rafael/0000-0002-3354-2442; okun, eitan/0000-0001-8474-1487;
Martin-Montalvo, Alejandro/0000-0002-3886-5355; ,
rafael/0000-0003-2830-5693
FU Intramural Research Program of the National Institute on Aging; Bar Ilan
University; Gonda Multidisciplinary Brain Research Center
FX The authors' work was supported by the Intramural Research Program of
the National Institute on Aging, as well as by Bar Ilan University, The
Gonda Multidisciplinary Brain Research Center.
NR 59
TC 12
Z9 12
U1 1
U2 17
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0889-1591
EI 1090-2139
J9 BRAIN BEHAV IMMUN
JI Brain Behav. Immun.
PD FEB
PY 2014
VL 36
BP 90
EP 100
DI 10.1016/j.bbi.2013.10.013
PG 11
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 293BJ
UT WOS:000329946100012
PM 24145051
ER
PT J
AU Turnbull, AE
Ruhl, AP
Lau, BM
Mendez-Tellez, PA
Shanholtz, CB
Needham, DM
AF Turnbull, Alison E.
Ruhl, A. Parker
Lau, Bryan M.
Mendez-Tellez, Pedro A.
Shanholtz, Carl B.
Needham, Dale M.
TI Timing of Limitations in Life Support in Acute Lung Injury Patients: A
Multisite Study
SO CRITICAL CARE MEDICINE
LA English
DT Article
DE acute lung injury; intensive care; intensive care units; life support
care; prospective studies; respiration; artificial; resuscitation
orders; survival rate; terminal care; time factors; withholding
treatment
ID RESPIRATORY-DISTRESS-SYNDROME; OF-LIFE; NATIONAL-SURVEY; CRITICALLY-ILL;
ADVANCE DIRECTIVES; PHYSICAL FUNCTION; END; CARE; WITHDRAWAL; SURGEONS
AB Objective: Substantial variability exists in the timing of limitations in life support for critically ill patients. Our objective was to investigate how the timing of limitations in life support varies with changes in organ failure status and time since acute lung injury onset.
Design, Setting, and Patients: This evaluation was performed as part of a prospective cohort study evaluating 490 consecutive acute lung injury patients recruited from 11 ICUs at three teaching hospitals in Baltimore, MD.
Interventions: None.
Measurements: The primary exposure was proportion of days without improvement in Sequential Organ Failure Assessment score, evaluated as a daily time-varying exposure. The outcome of interest was a documented limitation in life support defined as any of the following: 1) no cardiopulmonary resuscitation, 2) do not reintubate, 3) no vasopressors, 4) no hemodialysis, 5) do not escalate care, or 6) other limitations (e.g., comfort care only).
Main Results: For medical ICU patients without improvement in daily Sequential Organ Failure Assessment score, the rate of limitation in life support tripled in the first 3 days after acute lung injury onset, increased again after day 5, and peaked at day 19. Compared with medical ICU patients, surgical ICU patients had a rate of limitations that was significantly lower during the first 5 days after acute lung injury onset. In all patients, more days without improvement in Sequential Organ Failure Assessment scores was associated with limitations in life support, independent of the absolute magnitude of the Sequential Organ Failure Assessment score.
Conclusions: Persistent organ failure is associated with an increase in the rate of limitations in life support independent of the absolute magnitude of Sequential Organ Failure Assessment score, and this association strengthens during the first weeks of treatment. During the first 5 days after acute lung injury onset, limitations were significantly more common in medical ICUs than surgical ICUs.
C1 [Turnbull, Alison E.; Lau, Bryan M.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21218 USA.
[Turnbull, Alison E.; Ruhl, A. Parker; Mendez-Tellez, Pedro A.; Needham, Dale M.] Johns Hopkins Univ, Sch Med, Outcomes Crit Illness & Surg OACIS Grp, Baltimore, MD USA.
[Ruhl, A. Parker; Needham, Dale M.] Johns Hopkins Univ, Sch Med, Div Pulm & Crit Care Med, Baltimore, MD USA.
[Ruhl, A. Parker] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA.
[Mendez-Tellez, Pedro A.] Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA.
[Shanholtz, Carl B.] Univ Maryland, Div Pulm & Crit Care Med, Baltimore, MD 21201 USA.
[Needham, Dale M.] Johns Hopkins Univ, Sch Med, Dept Phys Med & Rehabil, Baltimore, MD USA.
RP Turnbull, AE (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21218 USA.
EM turnbull@jhmi.edu
OI Shanholtz, Carl/0000-0003-3938-178X
FU Johns Hopkins University; National Institutes of Health (NIH), National
Institute on Aging [T32AG000247]; NIH; NIH (Acute Lung Injury
Specialized Centers of Clinically Oriented Research) [P050 HL 73994]
FX Dr. Turnbull received grant support from the Johns Hopkins University
Summer Scholars Program (scholarship for graduate students in public
health). Dr. Turnbull's institution received grant support from the
National Institutes of Health (NIH), National Institute on Aging
(T32AG000247-postdoctoral training grant). Dr. Shanholtz and his
institution received grant support from the NIH. Dr. Shanholtz received
support for article research from the NIH. Dr. Needham and his
institution received grant support from the NIH (Acute Lung Injury
Specialized Centers of Clinically Oriented Research grant-P050 HL
73994). The remaining authors have disclosed that they do not have any
potential conflicts of interest.
NR 33
TC 8
Z9 8
U1 2
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0090-3493
EI 1530-0293
J9 CRIT CARE MED
JI Crit. Care Med.
PD FEB
PY 2014
VL 42
IS 2
BP 296
EP 302
DI 10.1097/CCM.0b013e3182a272db
PG 7
WC Critical Care Medicine
SC General & Internal Medicine
GA 291WS
UT WOS:000329863400025
PM 23989178
ER
PT J
AU Miller, AC
Elamin, EM
Suffredini, AF
AF Miller, Andrew C.
Elamin, Elamin M.
Suffredini, Anthony F.
TI Inhaled Anticoagulation Regimens for the Treatment of Smoke
Inhalation-Associated Acute Lung Injury: A Systematic Review
SO CRITICAL CARE MEDICINE
LA English
DT Article
DE acute lung injury; anticoagulants; antithrombins; fibrinolytic agents;
heparin; smoke inhalation injury
ID BRONCHIAL BLOOD-FLOW; PULMONARY-FUNCTION; NEBULIZED HEPARIN;
N-ACETYLCYSTEINE; COMBINED BURN; AIRWAY-OBSTRUCTION; SHEEP;
ANTITHROMBIN; MORTALITY; THERAPY
AB Objective: Inhaled anticoagulation regimens are increasingly being used to manage smoke inhalation-associated acute lung injury. We systematically reviewed published and unpublished preclinical and clinical trial data to elucidate the effects of these regimens on lung injury severity, airway obstruction, ventilation, oxygenation, pulmonary infections, bleeding complications, and survival.
Data Sources: PubMed, Scopus, EMBASE, and Web of Science were searched to identify relevant published studies. Relevant unpublished studies were identified by searching the Australian and New Zealand Clinical Trials Registry, World Health Organization International Clinical Trials Registry Platform, Cochrane Library, ClinicalTrials.gov, MINDCULL.com, Current Controlled Trials, and Google.
Study Selection: Inclusion criteria were any preclinical or clinical study in which 1) animals or subjects experienced smoke inhalation exposure, 2) they were treated with nebulized or aerosolized anticoagulation regimens, including heparin, heparinoids, antithrombins, or fibrinolytics (e.g., tissue plasminogen activator), 3) a control and/or sham group was described for preclinical studies, and 4) a concurrent or historical control group described for clinical studies. Exclusion criteria were 1) the absence of a group treated with a nebulized or aerosolized anticoagulation regimen, 2) the absence of a control or sham group, and 3) case reports.
Data Extraction: Ninety-nine potentially relevant references were identified. Twenty-seven references met inclusion criteria including 19 preclinical references reporting 18 studies and eight clinical references reporting five clinical studies.
Data Synthesis: A systematic review of the literature is provided. Both clinical and methodological diversity precluded combining these studies in a meta-analysis.
Conclusions: The high mortality associated with smoke inhalation-associated acute lung injury results from airway damage, mucosal dysfunction, neutrophil infiltration, airway coagulopathy with cast formation, ventilation-perfusion mismatching with shunt, and barotrauma. Inhaled anticoagulation regimens in both preclinical and clinical studies improve survival and decrease morbidity without altering systemic markers of clotting and anticoagulation. In some preclinical and clinical studies, inhaled anticoagulants were associated with a favorable effect on survival. This approach appears sufficiently promising to merit a well-designed prospective study to validate its use in patients with severe smoke inhalation-associated acute lung injury requiring mechanical ventilation.
C1 [Miller, Andrew C.; Suffredini, Anthony F.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
[Miller, Andrew C.] Univ Pittsburgh, Med Ctr, Dept Internal Med, Div Pulm Allergy & Crit Care, Pittsburgh, PA USA.
[Elamin, Elamin M.] James A Haley Vet Hosp, Dept Internal Med, Div Pulm Crit Care & Sleep Med, Tampa, FL 33612 USA.
[Elamin, Elamin M.] Univ S Florida, Tampa, FL USA.
RP Miller, AC (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
EM andrew.miller3@nih.gov
OI Miller, Andrew/0000-0001-8474-5090
FU Clinical Center, National Institutes of Health; Veterans Administration
Hospital; National Institutes of Health
FX Supported, in part, by the Intramural Research Program of the Clinical
Center, National Institutes of Health, and the Veterans Administration
Hospital.; Dr. Elamin received support for travel from SuperDimension.
Dr. Suffredini received support for article research from the National
Institutes of Health. Dr. Miller disclosed that he does not have any
potential conflicts of interest.
NR 60
TC 19
Z9 22
U1 0
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0090-3493
EI 1530-0293
J9 CRIT CARE MED
JI Crit. Care Med.
PD FEB
PY 2014
VL 42
IS 2
BP 413
EP 419
DI 10.1097/CCM.0b013e3182a645e5
PG 7
WC Critical Care Medicine
SC General & Internal Medicine
GA 291WS
UT WOS:000329863400039
PM 24158173
ER
PT J
AU Li, Y
Wong, K
Giles, A
Jiang, JW
Lee, JW
Adams, AC
Kharitonenkov, A
Yang, Q
Gao, B
Guarente, L
Zang, MW
AF Li, Yu
Wong, Kimberly
Giles, Amber
Jiang, Jianwei
Lee, Jong Woo
Adams, Andrew C.
Kharitonenkov, Alexei
Yang, Qin
Gao, Bin
Guarente, Leonard
Zang, Mengwei
TI Hepatic SIRT1 Attenuates Hepatic Steatosis and Controls Energy Balance
in Mice by Inducing Fibroblast Growth Factor 21
SO GASTROENTEROLOGY
LA English
DT Article
DE Liver-Specific Disruption of Sirt1; Hepatocyte-Derived Hormone;
Metabolic Homeostasis; Obesity
ID ACTIVATED PROTEIN-KINASE; IMPROVES INSULIN SENSITIVITY; FATTY-ACID
OXIDATION; LIPID-METABOLISM; TRANSGENIC MICE; RECEPTOR; FGF21;
EXPENDITURE; ATHEROSCLEROSIS; INFLAMMATION
AB BACKGROUND & AIMS: The hepatocyte-derived hormone fibroblast growth factor 21 (FGF21) is a hormone-like regulator of metabolism. The nicotinamide adenine dinucleotide-dependent deacetylase SIRT1 regulates fatty acid metabolism through multiple nutrient sensors. Hepatic overexpression of SIRT1 reduces steatosis and glucose intolerance in obese mice. We investigated mechanisms by which SIRT1 controls hepatic steatosis in mice. METHODS: Liver-specific SIRT1 knockout (SIRT1 LKO) mice and their wild-type littermates (controls) were divided into groups that were placed on a normal chow diet, fasted for 24 hours, or fasted for 24 hours and then fed for 6 hours. Liver tissues were collected and analyzed by histologic examination, gene expression profiling, and real-time polymerase chain reaction assays. Human HepG2 cells were incubated with pharmacologic activators of SIRT1 (resveratrol or SRT1720) and mitochondrion oxidation consumption rate and immunoblot analyses were performed. FGF21 was overexpressed in SIRT1 LKO mice using an adenoviral vector. Energy expenditure was assessed by indirect calorimetry. RESULTS: Prolonged fasting induced lipid deposition in livers of control mice, but severe hepatic steatosis in SIRT1 LKO mice. Gene expression analysis showed that fasting upregulated FGF21 in livers of control mice but not in SIRT1 LKO mice. Decreased hepatic and circulating levels of FGF21 in fasted SIRT1 LKO mice were associated with reduced hepatic expression of genes involved in fatty acid oxidation and ketogenesis, and increased expression of genes that control lipogenesis, compared with fasted control mice. Resveratrol or SRT1720 each increased the transcriptional activity of the FGF21 promoter (-2070/+117) and levels of FGF21 messenger RNA and protein in HepG2 cells. Surprisingly, SIRT1 LKO mice developed late-onset obesity with impaired whole-body energy expenditure. Hepatic overexpression of FGF21 in SIRT1 LKO mice increased the expression of genes that regulate fatty acid oxidation, decreased fasting-induced steatosis, reduced obesity, increased energy expenditure, and promoted browning of white adipose tissue. CONCLUSIONS: SIRT1-mediated activation of FGF21 prevents liver steatosis caused by fasting. This hepatocyte-derived endocrine signaling appears to regulate expression of genes that control a brown fat-like program in white adipose tissue, energy expenditure, and adiposity. Strategies to activate SIRT1 or FGF21 could be used to treat fatty liver disease and obesity.
C1 [Li, Yu; Wong, Kimberly; Giles, Amber; Jiang, Jianwei; Lee, Jong Woo; Zang, Mengwei] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[Adams, Andrew C.; Kharitonenkov, Alexei] Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA.
[Yang, Qin] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA.
[Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD USA.
[Guarente, Leonard] MIT, Dept Biol, Paul F Glenn Lab, Cambridge, MA USA.
RP Zang, MW (reprint author), Boston Univ, Sch Med, Dept Med, 650 Albany St,X725, Boston, MA 02118 USA.
EM liyu@gmail.com; mwzang1@bu.edu
FU National Institutes of Health [RO1 DK076942, R21 AA021181]; Robert
Dawson Evans Faculty Merit Award; Wing Tat Lee Award; Boston University
Clinical and Translational Science Institute (CTSI) [UL1RR025771]
FX This work was supported by National Institutes of Health grants RO1
DK076942 and R21 AA021181, the Robert Dawson Evans Faculty Merit Award,
the Wing Tat Lee Award (M.Z.), and by the Boston University Clinical and
Translational Science Institute (CTSI) subsidy fund UL1RR025771 (Y.L.).
NR 36
TC 52
Z9 57
U1 2
U2 34
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
EI 1528-0012
J9 GASTROENTEROLOGY
JI Gastroenterology
PD FEB
PY 2014
VL 146
IS 2
BP 539
EP +
DI 10.1053/j.gastro.2013.10.059
PG 18
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 290LE
UT WOS:000329757800034
PM 24184811
ER
PT J
AU Kroy, DC
Ciuffreda, D
Cooperrider, JH
Tomlinson, M
Hauck, GD
Aneja, J
Berger, C
Wolski, D
Carrington, M
Wherry, EJ
Chung, RT
Tanabe, KK
Elias, N
Freeman, GJ
de Kruyff, RH
Misdraji, J
Kim, AY
Lauer, GM
AF Kroy, Daniela C.
Ciuffreda, Donatella
Cooperrider, Jennifer H.
Tomlinson, Michelle
Hauck, Garrett D.
Aneja, Jasneet
Berger, Christoph
Wolski, David
Carrington, Mary
Wherry, E. John
Chung, Raymond T.
Tanabe, Kenneth K.
Elias, Nahel
Freeman, Gordon J.
de Kruyff, Rosemarie H.
Misdraji, Joseph
Kim, Arthur Y.
Lauer, Georg M.
TI Liver Environment and HCV Replication Affect Human T-Cell Phenotype and
Expression of Inhibitory Receptors
SO GASTROENTEROLOGY
LA English
DT Article
DE Immune Regulation; Costimulation; T-Cell Exhaustion; Inflammation
ID C VIRUS-INFECTION; CHRONIC VIRAL-INFECTION; PD-1 EXPRESSION; CD8(+);
EXHAUSTION; LYMPHOCYTES; PERSISTENCE; SUBSETS; ANTIGEN; CD4(+)
AB BACKGROUND & AIMS: There is an unclear relationship between inhibitory receptor expression on T cells and their ability to control viral infections. Studies of human immune cells have been mostly limited to T cells from blood, which is often not the site of infection. We investigated the relationship between T-cell location, expression of inhibitory receptors, maturation, and viral control using blood and liver T cells from patients with hepatitis C virus (HCV) and other viral infections. METHODS: We analyzed 36 liver samples from HCV antibody-positive patients (30 from patients with chronic HCV infection, 5 from patients with sustained virological responses to treatment, and 1 from a patient with spontaneous clearance) with 19 paired blood samples and 51 liver samples from HCV-negative patients with 17 paired blood samples. Intrahepatic and circulating lymphocytes were extracted; T-cell markers and inhibitory receptors were quantified for total and virus-specific T cells by flow cytometry. RESULTS: Levels of the markers PD-1 and 2B4 (but not CD160, TIM-3, or LAG-3) were increased on intrahepatic T cells from healthy and diseased liver tissues compared with T cells from blood. HCV-specific intrahepatic CD8(+) T cells from patients with chronic HCV infection were distinct in that they expressed TIM-3 along with PD-1 and 2B4. In comparison, HCV-specific CD8(+) T cells from patients with sustained virological responses and T cells that recognized cytomegalovirus lacked TIM-3 but expressed higher levels of LAG-3; these cells also had different memory phenotypes and proliferative capacity. CONCLUSIONS: T cells from liver express different inhibitory receptors than T cells from blood, independent of liver disease. HCV-specific and cytomegalovirus-specific CD8(+) T cells can be differentiated based on their expression of inhibitory receptors; these correlate with their memory phenotype and levels of proliferation and viral control.
C1 [Kroy, Daniela C.; Ciuffreda, Donatella; Cooperrider, Jennifer H.; Tomlinson, Michelle; Hauck, Garrett D.; Aneja, Jasneet; Wolski, David; Chung, Raymond T.; Lauer, Georg M.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
[Tomlinson, Michelle; Misdraji, Joseph] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Tanabe, Kenneth K.] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA.
[Elias, Nahel] Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA.
[Kim, Arthur Y.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Berger, Christoph; Carrington, Mary; Freeman, Gordon J.; de Kruyff, Rosemarie H.; Kim, Arthur Y.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Berger, Christoph; Carrington, Mary] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA.
[Carrington, Mary] Frederick Natl Lab Canc Res, SAIC Frederick Inc, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD USA.
[Wherry, E. John] Univ Penn, Dept Microbiol, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Wherry, E. John] Univ Penn, Inst Immunol, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Freeman, Gordon J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[de Kruyff, Rosemarie H.] Childrens Hosp, Div Immunol, Boston, MA 02115 USA.
RP Lauer, GM (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St, Boston, MA 02114 USA.
EM glauer@mgh.harvard.edu
FU Deutsche Forschungsgemeinschaft [Kr3839/1-1]; National Institutes of
Health (NIH) [U19 AI082630]; NIH [U19 AI066345, R01 AI105035, P01
AI054456, R01 A1089955]; Frederick National Laboratory for Cancer
Research [HHSN261200800001E]; NIH, Frederick National Laboratory, Center
for Cancer Research
FX Supported by Deutsche Forschungsgemeinschaft (Kr3839/1-1 to D. C. K.),
National Institutes of Health (NIH) grant U19 AI082630 (to G. M. L.,
E.J.W., R. T. C., G.J.F., and J.M.), NIH grant U19 AI066345 (to G. M.
L., A.Y.K.), NIH grant R01 AI105035 (to G. M. L.), NIH grant P01
AI054456 (to R. D. K. and G.J.F.), and NIH grant R01 A1089955 (to R. D.
K. and G.J.F.). This project was 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 US government. This
research was also supported in part by the Intramural Research Program
of the NIH, Frederick National Laboratory, Center for Cancer Research.
NR 25
TC 26
Z9 30
U1 1
U2 6
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
EI 1528-0012
J9 GASTROENTEROLOGY
JI Gastroenterology
PD FEB
PY 2014
VL 146
IS 2
BP 550
EP 561
DI 10.1053/j.gastro.2013.10.022
PG 12
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 290LE
UT WOS:000329757800035
PM 24148617
ER
PT J
AU Wani, S
Drahos, J
Cook, MB
Rastogi, A
Bansal, A
Yen, R
Sharma, P
Das, A
AF Wani, Sachin
Drahos, Jennifer
Cook, Michael B.
Rastogi, Amit
Bansal, Ajay
Yen, Roy
Sharma, Prateek
Das, Ananya
TI Comparison of endoscopic therapies and surgical resection in patients
with early esophageal cancer: a population-based study
SO GASTROINTESTINAL ENDOSCOPY
LA English
DT Article
ID HIGH-GRADE DYSPLASIA; LONG-TERM SURVIVAL; BARRETTS-ESOPHAGUS;
INTRAMUCOSAL ADENOCARCINOMA; RADIOFREQUENCY ABLATION; MANAGEMENT;
SURVEILLANCE; RISK
AB Background: Outcome data comparing endoscopic eradication therapy (EET) and esophagectomy are limited in patients with early esophageal cancer (EC).
Objective: To compare overall survival and EC-related mortality in patients with early EC treated with EET and esophagectomy.
Design and Setting: Population-based study.
Patients: Patients with early EC (stages T0 and T1) were identified from the Surveillance, Epidemiology, and End Results database (1998-2009). Demographics, tumor specific data, and survival were compared. Cox proportional hazards regression models were used to evaluate the association between treatment and EC-specific mortality.
Intervention: EET and esophagectomy.
Main Outcome Measurements: Mid- (2 years) and long- (5 years) term overall survival and EC-specific mortality, outcomes based on histology and stage, treatment patterns, and predictors of cancer-specific mortality.
Results: A total of 430 (21%) and 1586 (79%) patients underwent EET and esophagectomy, respectively. There was no difference in the 2-year (EET: 10.5% vs esophagectomy: 12.7%, P = .27). and 5-year (EET: 36.7% vs esophagectomy: 42.8%, P = .16) EC-related mortality rates between the 2 groups. EET patients had higher mortality rates attributed to non-EC causes (5 years: 46.6% vs 20.6%, P < .001). Similar results were noted when comparisons were limited to patients with stage T0 and T1a disease and esophageal adenocarcinoma. There was no difference in EC-specific mortality in the EET compared with the surgery group (hazard ratio 1.4; 95% confidence interval, 0.9-2.03). Variables associated with mortality were older age, year of diagnosis, radiation therapy, higher stage, and esophageal squamous cell carcinoma.
Limitations: Comorbidities and recurrence rates were not available.
Conclusions: This population-based study demonstrates comparable mid-and long-term EC-related mortality in patients with early EC undergoing EET and surgical resection.
C1 [Wani, Sachin; Yen, Roy] Univ Colorado, Anschutz Med Ctr, Div Gastroenterol & Hepatol, Aurora, CO 80045 USA.
[Wani, Sachin] Vet Affairs Med Ctr, Div Gastroenterol & Hepatol, Denver, CO USA.
[Drahos, Jennifer; Cook, Michael B.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Rastogi, Amit; Bansal, Ajay; Sharma, Prateek] Univ Kansas, Sch Med, Kansas City, MO USA.
[Rastogi, Amit; Bansal, Ajay; Sharma, Prateek] Vet Affairs Med Ctr, Kansas City, MO USA.
[Das, Ananya] Arizona Ctr Digest Hlth, Gilbert, AZ USA.
RP Wani, S (reprint author), Univ Colorado, Anschutz Med Ctr, Vet Affairs Med Ctr, Div Gastroenterol & Hepatol, Mail Stop F735,1635 Aurora Court,Room 2-031, Aurora, CO 80045 USA.
RI Cook, Michael/A-5641-2009
OI Cook, Michael/0000-0002-0533-7302
FU AGA Takeda Research Scholar Award in GERD and Barrett's esophagus;
National Institutes of Health
FX Dr Wani is supported by the AGA Takeda Research Scholar Award in GERD
and Barrett's esophagus. Dr Drahos and Dr Cook are supported by the
Intramural Program of the National Institutes of Health. The other
authors disclosed no financial relationships relevant to this
publication.
NR 25
TC 18
Z9 19
U1 1
U2 7
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0016-5107
EI 1097-6779
J9 GASTROINTEST ENDOSC
JI Gastrointest. Endosc.
PD FEB
PY 2014
VL 79
IS 2
BP 224
EP 232
DI 10.1016/j.gie.2013.08.002
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 290LO
UT WOS:000329759200010
PM 24060519
ER
PT J
AU Amos, C
George, V
Bailey-Wilson, J
Demenais, F
AF Amos, Christopher
George, Varghese
Bailey-Wilson, Joan
Demenais, Florence
TI George Bonney (1947-2013) Remembered
SO GENETIC EPIDEMIOLOGY
LA English
DT Biographical-Item
ID REGRESSIVE MODELS; BREAST-CANCER; REPRODUCTIVE FACTORS; TRAITS;
ASSOCIATION; POPULATION; GENE
C1 Dept Community & Family Med, Dartmouth Coll, Hanover, NH USA.
Georgia Regents Univ, Dept Biostatist Epidemiol, Augusta, GA USA.
Natl Human Genome Res Inst, Natl Inst Hlth, Inherited Dis Res Branch, Baltimore, MD USA.
INSERM, Genet Variat & Human Dis Unit, U946, Paris, France.
Univ Paris Diderot, Inst Univ dHematol, Sorbonne Paris Cite, Paris, France.
RP Amos, C (reprint author), Dartmouth Coll, Dept Community & Family Med, 46 Centerra Pkwy,Suite 330, Lebanon, NH 03750 USA.
EM christopher.i.amos@dartmouth.edu
RI Demenais, Florence/G-3298-2013;
OI Demenais, Florence/0000-0001-8361-0936; Bailey-Wilson,
Joan/0000-0002-9153-2920
NR 17
TC 0
Z9 0
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
EI 1098-2272
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD FEB
PY 2014
VL 38
IS 2
BP 95
EP 96
DI 10.1002/gepi.21780
PG 2
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 291OF
UT WOS:000329837300001
ER
PT J
AU Ghosh, A
Hartge, P
Kraft, P
Joshi, AD
Ziegler, RG
Barrdahl, M
Chanock, SJ
Wacholder, S
Chatterjee, N
AF Ghosh, Arpita
Hartge, Patricia
Kraft, Peter
Joshi, Amit D.
Ziegler, Regina G.
Barrdahl, Myrto
Chanock, Stephen J.
Wacholder, Sholom
Chatterjee, Nilanjan
TI Leveraging Family History in Population-Based Case-Control Association
Studies
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE disease history in family members; first-degree relatives;
meta-analysis; more powerful test for genetic association
ID GENOME-WIDE ASSOCIATION; LINE CHARACTERISTICS; PROSTATE-CANCER; COMMON
DISEASES; RARE VARIANTS; NURSES HEALTH; LIFE-STYLE; RISK; COHORT; GENES
AB Population-based epidemiologic studies often gather information from study participants on disease history among their family members. Although investigators widely recognize that family history will be associated with genotypes of the participants at disease susceptibility loci, they commonly ignore such information in primary genetic association analyses. In this report, we propose a simple approach to association testing by incorporating family history information as a phenotype. We account for the expected attenuation in strength of association of the genotype of study participants with family history under Mendelian transmission. The proposed analysis can be performed using standard statistical software adopting either a meta- or pooled-analysis framework. Re-analysis of a total of 115 known susceptibility single-nucleotide polymorphisms, discovered through genome-wide association studies for several disease traits, indicates that incorporation of family history information can increase efficiency by as much as 40%. Efficiency gain depends on the type of design used for conducting the primary study, extent of family history, and accuracy and completeness of reporting.
C1 [Ghosh, Arpita] Publ Hlth Fdn India, New Delhi, India.
[Hartge, Patricia; Ziegler, Regina G.; Chanock, Stephen J.; Wacholder, Sholom; Chatterjee, Nilanjan] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
[Kraft, Peter; Joshi, Amit D.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Barrdahl, Myrto] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
RP Chatterjee, N (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr Suite 7-E146,MSC 9780, Rockville, MD 20852 USA.
EM chattern@mail.nih.gov
FU U.S. National Institutes of Health, National Cancer Institute
[U01-CA98233, U19-CA148065, U01-CA98710, U01-CA98216, U01-CA98758];
NIH/NCI, Division of Cancer Epidemiology and Genetics; NIH Genes,
Environment and Health Initiative [GEI] [U01HG004399, U01HG004424];
National Institutes of Health [CA87969, CA55075, DK58845,
HHSN268200625226C, UL1RR025005]; National Heart, Lung, and Blood
Institute [N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019,
N01-HC-55020, N01-HC-55021, N01-HC-55022, R01HL087641, R01HL59367,
R01HL086694]; National Human Genome Research Institute [U01HG004402];
NIH Roadmap for Medical Research
FX Part of Dr. Ghosh's research and Drs. Hartge, Ziegler, Chanock,
Wacholder, and Chatterjee's research was supported by the Intramural
Research Program of the Division of Cancer Epidemiology and Genetics of
the National Cancer Institute. The breast cancer dataset was funded by
the U.S. National Institutes of Health, National Cancer Institute
(cooperative agreements U01-CA98233 and U19-CA148065 to David J. Hunter,
U01-CA98710 to Michael J. Thun, U01-CA98216 to Elio Riboli and Rudolf
Kaaks, and U01-CA98758 to Brian E. Henderson, and Intramural Research
Program of NIH/NCI, Division of Cancer Epidemiology and Genetics).;
Funding support for the GWAS of Gene and Environment Initiatives in T2D
was provided through the NIH Genes, Environment and Health Initiative
[GEI] (U01HG004399). The human subjects participating in the GWAS derive
from The Nurses' Health Study and Health Professionals' Follow-up study
and these studies are supported by National Institutes of Health grants
CA87969, CA55075, and DK58845. Assistance with phenotype harmonization
and genotype cleaning, as well as with general study coordination, was
provided by the Gene Environment Association Studies, GENEVA
Coordinating Center (U01HG004446). Assistance with data cleaning was
provided by the National Center for Biotechnology Information. Funding
support for genotyping, which was performed at the Broad Institute of
MIT and Harvard, was provided by the NIH GEI (U01HG004424). The datasets
used for the analyses described in this manuscript were obtained from
dbGaP at [http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gap] through dbGaP
accession number [phs000091].; The Atherosclerosis Risk in Communities
Study is carried out as a collaborative study supported by National
Heart, Lung, and Blood Institute contracts N01-HC-55015, N01-HC-55016,
N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022,
R01HL087641, R01HL59367, and R01HL086694; National Human Genome Research
Institute contract U01HG004402; and National Institutes of Health
contract HHSN268200625226C. The authors thank the staff and participants
of the ARIC study for their important contributions. Infrastructure was
partly supported by Grant Number UL1RR025005, a component of the
National Institutes of Health and NIH Roadmap for Medical Research.
NR 31
TC 2
Z9 2
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
EI 1098-2272
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD FEB
PY 2014
VL 38
IS 2
BP 114
EP 122
DI 10.1002/gepi.21785
PG 9
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 291OF
UT WOS:000329837300004
PM 24408355
ER
PT J
AU Allen, KM
Fung, SJ
Rothmond, DA
Noble, PL
Weickert, CS
AF Allen, K. M.
Fung, S. J.
Rothmond, D. A.
Noble, P. L.
Weickert, C. Shannon
TI Gonadectomy Increases Neurogenesis in the Male Adolescent Rhesus Macaque
Hippocampus
SO HIPPOCAMPUS
LA English
DT Review
DE schizophrenia; neuronal survival; testosterone; development; sex
steroids
ID NEWLY GENERATED NEURONS; IMMATURE DENTATE GYRUS; SERUM TESTOSTERONE
LEVELS; STEM-CELL PROLIFERATION; ADULT SONGBIRD BRAIN; MALE RATS;
NEGATIVE SYMPTOMS; CHRONIC-SCHIZOPHRENIA; SYNAPTIC INTEGRATION;
SEX-DIFFERENCES
AB New neurons are continuously produced in the subgranular zone of the adult hippocampus and can modulate hippocampal plasticity across life. Adolescence is characterized by dramatic changes in sex hormone levels, and social and emotional behaviors. It is also an age for increased risk of psychiatric disorders, including schizophrenia, which may involve altered hippocampal neurogenesis. The extent to which testosterone and other testicular hormones modulate hippocampal neurogenesis and adolescent behavioral development is unclear. This study aimed to determine if removal of testicular hormones during adolescence alters neurogenesis in the male rhesus macaque hippocampus. We used stereology to examine levels of cell proliferation, cell survival and neuronal differentiation in late adolescent male rhesus macaques (4.6-yrs old) that had previously been gonadectomized or sham operated prior to puberty (2.4-yrs old). While the absence of adolescent testicular hormones had no effect on cell proliferation, cell survival was increased by 65% and indices of immature neuronal differentiation were increased by 56% in gonadectomized monkeys compared to intact monkeys. We show for the first time that presence of circulating testicular hormones, including testosterone, may decrease neuronal survival in the primate hippocampus during adolescence. Our findings are in contrast to existing studies in adults where testosterone tends to be a pro-survival factor and demonstrate that testicular hormones may reduce hippocampal neurogenesis during the age typical of schizophrenia onset. (c) 2013 Wiley Periodicals, Inc.
C1 [Allen, K. M.; Fung, S. J.; Rothmond, D. A.; Weickert, C. Shannon] Schizophrenia Res Inst, Sydney, NSW 2010, Australia.
[Allen, K. M.; Fung, S. J.; Rothmond, D. A.; Weickert, C. Shannon] Neurosci Res Australia, Schizophrenia Res Lab, Randwick, NSW 2031, Australia.
[Allen, K. M.; Fung, S. J.; Weickert, C. Shannon] Univ New S Wales, Sch Psychiat, Sydney, NSW 2052, Australia.
[Noble, P. L.] NIMH IRP Nonhuman Primate Core, Bethesda, MD USA.
RP Weickert, CS (reprint author), Neurosci Res Australia, Barker St, Randwick, NSW 2031, Australia.
EM cyndi@neura.edu.au
RI Allen, Katherine/C-9664-2011
OI Allen, Katherine/0000-0002-2092-461X
FU National Health and Medical Research Council (Australia) [1021970];
Schizophrenia Research Institute (NSW Ministry of Health); Schizophrenia
Research Institute (Macquarie Group Foundation); University of UNSW;
Neuroscience Research Australia; Australian Postgraduate Award
(University of New South Wales)
FX Grant sponsor: National Health and Medical Research Council (Australia);
Grant number: 1021970; Grant sponsors: Schizophrenia Research Institute
(NSW Ministry of Health and the Macquarie Group Foundation); the
University of UNSW; Neuroscience Research Australia; Australian
Postgraduate Award (University of New South Wales).
NR 103
TC 8
Z9 9
U1 0
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1050-9631
EI 1098-1063
J9 HIPPOCAMPUS
JI Hippocampus
PD FEB
PY 2014
VL 24
IS 2
BP 225
EP 238
DI 10.1002/hipo.22217
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA 292CJ
UT WOS:000329879300009
PM 24123729
ER
PT J
AU Faupel-Badger, JM
Duggan, MA
Sherman, ME
Garcia-Closas, M
Yang, XHR
Lissowska, J
Brinton, LA
Peplonska, B
Vonderhaar, BK
Figueroa, JD
AF Faupel-Badger, Jessica M.
Duggan, Maire A.
Sherman, Mark E.
Garcia-Closas, Montserrat
Yang, Xiaohong R.
Lissowska, Jolanta
Brinton, Louise A.
Peplonska, Beata
Vonderhaar, Barbara K.
Figueroa, Jonine D.
TI Prolactin Receptor Expression and Breast Cancer: Relationships with
Tumor Characteristics among Pre- and Post-menopausal Women in a
Population-Based Case-Control Study from Poland
SO HORMONES & CANCER
LA English
DT Article
ID MAMMARY-GLAND DEVELOPMENT; PLASMA PROLACTIN; RISK-FACTORS; CARCINOMA;
GENE; PREMENOPAUSAL; MULTIPLE; ISOFORMS; THERAPY; HORMONE
AB Previous studies have found an association between elevated circulating prolactin levels and increased risk of breast cancer. Prolactin stimulates breast cancer cell proliferation, migration, and survival via binding to the cell-surface prolactin receptor. The association of prolactin receptor expression with breast tumorigenesis remains unclear as studies that have focused on this association have had limited sample size and/or information about tumor characteristics. Here, we examined the association of prolactin expression with tumor characteristics among 736 cases, from a large population-based case-control study of breast cancer conducted in Poland (2000-2003), with detailed risk factor and pathology data. Tumors were centrally reviewed and prepared as tissue microarrays for immunohistochemical analysis of prolactin receptor expression. Association of prolactin receptor expression across strata of tumor characteristics was evaluated using chi (2) analysis and logistic regression. Prolactin receptor expression did not vary by menopausal status; therefore, data from pre- and post-menopausal women were combined in the analyses. Approximately 83 % of breast cancers were categorized as strong prolactin receptor staining. Negative/low prolactin receptor expression was independently associated with poorly differentiated (p = 1.2 x 10(-08)) and larger tumors (p = 0.0005). These associations were independent of estrogen receptor expression. This is the largest study to date in which the association of prolactin receptor expression with tumor characteristics has been evaluated. These data provide new avenues from which to explore the associations of the prolactin/prolactin receptor signaling network with breast tumorigenesis.
C1 [Faupel-Badger, Jessica M.] NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA.
[Duggan, Maire A.] Univ Calgary, Dept Pathol & Lab Med, Calgary, AB T2N 2T9, Canada.
[Sherman, Mark E.; Garcia-Closas, Montserrat; Brinton, Louise A.; Figueroa, Jonine D.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Yang, Xiaohong R.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Garcia-Closas, Montserrat] Inst Canc Res, Sutton, Surrey, England.
[Lissowska, Jolanta] Ctr Canc, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
[Lissowska, Jolanta] M Sklodowska Curie Inst Oncol, Warsaw, Poland.
[Peplonska, Beata] Nofer Inst Occupat Med, Dept Environm Epidemiol, Lodz, Poland.
[Vonderhaar, Barbara K.] NCI, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Faupel-Badger, JM (reprint author), NCI, Canc Prevent Fellowship Program, 9609 Med Ctr Dr,2W-172, Bethesda, MD 20892 USA.
EM badgerje@mail.nih.gov
RI Garcia-Closas, Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015;
OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton,
Louise/0000-0003-3853-8562; Lissowska, Jolanta/0000-0003-2695-5799
FU Intramural Research Funds of the National Cancer Institute, Department
of Health and Human Services, USA; Intramural Research Programs of the
Division of Cancer Epidemiology and Genetics and Center for Cancer
Research of the National Cancer Institute; Cancer Prevention Fellowship
Program, Center for Cancer Training, NCI
FX We thank Pei Chao and Michael Stagner from Information Management
Services (Sliver Spring, MD, USA), for their valuable contributions to
the data management aspects of the study. We also thank the
participants, physicians, pathologists, nurses, and interviewers from
participating centers in Poland for their efforts during the field-work.
The study was funded by Intramural Research Funds of the National Cancer
Institute, Department of Health and Human Services, USA. This research
was supported by the Intramural Research Programs of the Division of
Cancer Epidemiology and Genetics and Center for Cancer Research of the
National Cancer Institute. Dr Faupel-Badger's research was also
supported by the Cancer Prevention Fellowship Program, Center for Cancer
Training, NCI.
NR 36
TC 4
Z9 4
U1 0
U2 13
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1868-8497
EI 1868-8500
J9 HORM CANCER-US
JI Horm. Cancer
PD FEB
PY 2014
VL 5
IS 1
BP 42
EP 50
DI 10.1007/s12672-013-0165-7
PG 9
WC Oncology; Endocrinology & Metabolism
SC Oncology; Endocrinology & Metabolism
GA 292YX
UT WOS:000329939700005
PM 24249584
ER
PT J
AU Chen, GB
Liu, NJ
Klimentidis, YC
Zhu, XF
Zhi, DG
Wang, XJ
Lou, XY
AF Chen, Guo-Bo
Liu, Nianjun
Klimentidis, Yann C.
Zhu, Xiaofeng
Zhi, Degui
Wang, Xujing
Lou, Xiang-Yang
TI A unified GMDR method for detecting gene-gene interactions in family and
unrelated samples with application to nicotine dependence
SO HUMAN GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; MULTIFACTOR-DIMENSIONALITY REDUCTION;
POPULATION STRATIFICATION; ENVIRONMENT INTERACTIONS; COMBINATORIAL
APPROACH; MISSING HERITABILITY; SUBUNIT GENE; DISEASES; CHRNA4; BDNF
AB Gene-gene and gene-environment interactions govern a substantial portion of the variation in complex traits and diseases. In convention, a set of either unrelated or family samples are used in detection of such interactions; even when both kinds of data are available, the unrelated and the family samples are analyzed separately, potentially leading to loss in statistical power. In this report, to detect gene-gene interactions we propose a generalized multifactor dimensionality reduction method that unifies analyses of nuclear families and unrelated subjects within the same statistical framework. We used principal components as genetic background controls against population stratification, and when sibling data are included, within-family control were used to correct for potential spurious association at the tested loci. Through comprehensive simulations, we demonstrate that the proposed method can remarkably increase power by pooling unrelated and offspring's samples together as compared with individual analysis strategies and the Fisher's combining p value method while it retains a controlled type I error rate in the presence of population structure. In application to a real dataset, we detected one significant tetragenic interaction among CHRNA4, CHRNB2, BDNF, and NTRK2 associated with nicotine dependence in the Study of Addiction: Genetics and Environment sample, suggesting the biological role of these genes in nicotine dependence development.
C1 [Chen, Guo-Bo; Liu, Nianjun; Klimentidis, Yann C.; Zhi, Degui; Lou, Xiang-Yang] Univ Alabama Birmingham, Dept Biostat, Sect Stat Genet, Birmingham, AL 35294 USA.
[Zhu, Xiaofeng] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA.
[Wang, Xujing] NHLBI, Bioinformat & Syst Biol Core, NIH, Bethesda, MD 20892 USA.
RP Lou, XY (reprint author), Univ Alabama Birmingham, Dept Biostat, Sect Stat Genet, 1665 Univ Blvd,RPHB 327, Birmingham, AL 35294 USA.
EM xylou@uab.edu
RI Klimentidis, Yann/B-2348-2015;
OI Klimentidis, Yann/0000-0002-6065-4044; Chen, Guo-Bo/0000-0001-5475-8237
FU National Institutes of Health [DA025095, GM081488, GM077490, HG003054,
DK080100]; NIH Genes, Environment and Health Initiative (GEI) [U01
HG004422]
FX This work was funded in part by the National Institutes of Health Grants
DA025095, GM081488, GM077490, HG003054, and DK080100. Funding support
for the Study of Addiction: Genetics and Environment (SAGE) was provided
through the NIH Genes, Environment and Health Initiative (GEI) (U01
HG004422). The datasets used for the analyses described in this
manuscript was obtained from the database of Genotypes and Phenotypes
(dbGaP) found at
http://www.ncbi.nlm.nih.gov/projects/gap/cgibin/study.cgi?study_id=phs00
0092.v1.p1 through dbGaP accession number phs000092.v1.p.
NR 30
TC 6
Z9 6
U1 1
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-6717
EI 1432-1203
J9 HUM GENET
JI Hum. Genet.
PD FEB
PY 2014
VL 133
IS 2
BP 139
EP 150
DI 10.1007/s00439-013-1361-9
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA 288ZY
UT WOS:000329652000002
PM 24057800
ER
PT J
AU De Vivo, I
Prescott, J
Setiawan, VW
Olson, SH
Wentzensen, N
Attia, J
Black, A
Brinton, L
Chen, C
Chen, C
Cook, LS
Crous-Bou, M
Doherty, J
Dunning, AM
Easton, DF
Friedenreich, CM
Garcia-Closas, M
Gaudet, MM
Haiman, C
Hankinson, SE
Hartge, P
Henderson, BE
Holliday, E
Horn-Ross, PL
Hunter, DJ
Le Marchand, L
Liang, XL
Lissowska, J
Long, JR
Lu, LG
Magliocco, AM
McEvoy, M
O'Mara, TA
Orlow, I
Painter, JN
Pooler, L
Rastogi, R
Rebbeck, TR
Risch, H
Sacerdote, C
Schumacher, F
Scott, RJ
Sheng, X
Shu, XO
Spurdle, AB
Thompson, D
VanDen Berg, D
Weiss, NS
Xia, L
Xiang, YB
Yang, HP
Yu, H
Zheng, W
Chanock, S
Kraft, P
AF De Vivo, Immaculata
Prescott, Jennifer
Setiawan, Veronica Wendy
Olson, Sara H.
Wentzensen, Nicolas
Attia, John
Black, Amanda
Brinton, Louise
Chen, Chu
Chen, Constance
Cook, Linda S.
Crous-Bou, Marta
Doherty, Jennifer
Dunning, Alison M.
Easton, Douglas F.
Friedenreich, Christine M.
Garcia-Closas, Montserrat
Gaudet, Mia M.
Haiman, Christopher
Hankinson, Susan E.
Hartge, Patricia
Henderson, Brian E.
Holliday, Elizabeth
Horn-Ross, Pamela L.
Hunter, David J.
Le Marchand, Loic
Liang, Xiaolin
Lissowska, Jolanta
Long, Jirong
Lu, Lingeng
Magliocco, Anthony M.
McEvoy, Mark
O'Mara, Tracy A.
Orlow, Irene
Painter, Jodie N.
Pooler, Loreall
Rastogi, Radhai
Rebbeck, Timothy R.
Risch, Harvey
Sacerdote, Carlotta
Schumacher, Fredrick
Scott, Rodney J.
Sheng, Xin
Shu, Xiao-ou
Spurdle, Amanda B.
Thompson, Deborah
VanDen Berg, David
Weiss, Noel S.
Xia, Lucy
Xiang, Yong-Bing
Yang, Hannah P.
Yu, Herbert
Zheng, Wei
Chanock, Stephen
Kraft, Peter
CA Australian Natl Endometrial Canc
TI Genome-wide association study of endometrial cancer in E2C2
SO HUMAN GENETICS
LA English
DT Article
ID COLORECTAL-CANCER; SUSCEPTIBILITY LOCI; PROSTATE-CANCER; OVARIAN-CANCER;
COLON-CANCER; YOUNG-WOMEN; RISK; EPIDEMIOLOGY; POPULATION; CARCINOMA
AB Endometrial cancer (EC), a neoplasm of the uterine epithelial lining, is the most common gynecological malignancy in developed countries and the fourth most common cancer among US women. Women with a family history of EC have an increased risk for the disease, suggesting that inherited genetic factors play a role. We conducted a two-stage genome-wide association study of Type I EC. Stage 1 included 5,472 women (2,695 cases and 2,777 controls) of European ancestry from seven studies. We selected independent single-nucleotide polymorphisms (SNPs) that displayed the most significant associations with EC in Stage 1 for replication among 17,948 women (4,382 cases and 13,566 controls) in a multiethnic population (African America, Asian, Latina, Hawaiian and European ancestry), from nine studies. Although no novel variants reached genome-wide significance, we replicated previously identified associations with genetic markers near the HNF1B locus. Our findings suggest that larger studies with specific tumor classification are necessary to identify novel genetic polymorphisms associated with EC susceptibility.
C1 [De Vivo, Immaculata; Prescott, Jennifer; Crous-Bou, Marta; Hankinson, Susan E.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA.
[De Vivo, Immaculata; Prescott, Jennifer; Crous-Bou, Marta; Hankinson, Susan E.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[De Vivo, Immaculata; Chen, Chu; Crous-Bou, Marta; Hunter, David J.; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Setiawan, Veronica Wendy; Haiman, Christopher; Henderson, Brian E.; Pooler, Loreall; Sheng, Xin; VanDen Berg, David; Xia, Lucy] Univ So Calif, Los Angeles, CA USA.
[Olson, Sara H.; Liang, Xiaolin; Orlow, Irene; Rastogi, Radhai] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Wentzensen, Nicolas; Black, Amanda; Brinton, Louise; Hartge, Patricia; Yang, Hannah P.; Chanock, Stephen] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[O'Mara, Tracy A.; Painter, Jodie N.; Spurdle, Amanda B.; Australian Natl Endometrial Canc] Queensland Inst Med Res, Div Genet & Populat Hlth, Brisbane, Qld 4006, Australia.
[Attia, John; McEvoy, Mark] Univ Newcastle, Sch Med & Publ Hlth, Ctr Clin Epidemiol & Biostat, Newcastle, NSW 2300, Australia.
[Attia, John] Univ Newcastle, John Hunter Hosp, Hunter Med Res Inst, Dept Gen Med, Newcastle, NSW 2300, Australia.
[Chen, Constance] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Cook, Linda S.] Univ New Mexico, Albuquerque, NM 87131 USA.
[Cook, Linda S.; Friedenreich, Christine M.] Alberta Hlth Serv, Dept Populat Hlth Res, Div Canc Care, Calgary, AB, Canada.
[Doherty, Jennifer] Dartmouth Coll, Geisel Sch Med, Lebanon, NH 03756 USA.
[Dunning, Alison M.] Univ Cambridge, CCGE, Strangeways Res Lab, Cambridge, England.
[Dunning, Alison M.; Easton, Douglas F.; Garcia-Closas, Montserrat; Thompson, Deborah] Univ Cambridge, Strangeways Res Lab, Dept Oncol, Cambridge, England.
[Easton, Douglas F.; Thompson, Deborah] Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Cambridge, England.
[Gaudet, Mia M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Hankinson, Susan E.] Univ Massachusetts, Div Biostat & Epidemiol, Amherst, MA 01003 USA.
[Holliday, Elizabeth] Univ Newcastle, Ctr Informat Based Med, Newcastle, NSW 2300, Australia.
[Holliday, Elizabeth] Univ Newcastle, Sch Med & Publ Hlth, Newcastle, NSW 2300, Australia.
[Holliday, Elizabeth; Scott, Rodney J.] John Hunter Hosp, Hunter Area Pathol Serv, Hunter Med Res Inst, Newcastle, NSW, Australia.
[Horn-Ross, Pamela L.; Schumacher, Fredrick] Canc Prevent Inst Calif, Fremont, CA USA.
[Le Marchand, Loic; Yu, Herbert] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
[Lissowska, Jolanta] M Sklodowska Curie Canc Ctr & Inst Oncol, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
[Long, Jirong; Shu, Xiao-ou; Zheng, Wei] Vanderbilt Univ, Med Ctr, Dept Med, Vanderbilt Epidemiol Ctr,VanderbiltIngram Canc Ct, Nashville, TN USA.
[Lu, Lingeng; Risch, Harvey] Yale Univ, Sch Publ Hlth, New Haven, CT USA.
[Magliocco, Anthony M.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA.
[Rebbeck, Timothy R.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Sacerdote, Carlotta] Ctr Canc Prevent CPO Piemonte, Turin, Italy.
[Sacerdote, Carlotta] Human Genet Fdn HuGeF, Turin, Italy.
[Scott, Rodney J.] Univ Newcastle, Ctr Informat Based Med, Newcastle, NSW 2300, Australia.
[Scott, Rodney J.] Univ Newcastle, Sch Biomed Sci & Pharm, Newcastle, NSW 2300, Australia.
[Weiss, Noel S.] Univ Washington, Seattle, WA 98195 USA.
[Xiang, Yong-Bing] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
RP De Vivo, I (reprint author), Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
EM nhidv@channing.harvard.edu
RI Garcia-Closas, Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015;
O'Mara, Tracy/M-7508-2016; Spurdle, Amanda/A-4978-2011;
OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton,
Louise/0000-0003-3853-8562; O'Mara, Tracy/0000-0002-5436-3232; Spurdle,
Amanda/0000-0003-1337-7897; Dunning, Alison
Margaret/0000-0001-6651-7166; Sacerdote, Carlotta/0000-0002-8008-5096;
Orlow, Irene/0000-0001-6234-6961
FU NCI, NIH [1R01 CA134958, 2R01 CA082838, P01 CA087969, R01 CA49449,
CA54281, CA128008, P01-CA77596, R01CA83918, P30-CA008748, R01 CA91019,
R01 CA77398]; American Cancer Society (ACS); Centers for Disease Control
and Prevention National Program of Cancer Registries; National Cancer
Institute Surveillance Epidemiology; End Results program; NIH [RO1
CA105212, RO1 CA 87538, RO1 CA75977, RO3 CA80636, NO1 HD23166, R35
CA39779, KO5 CA92002]; Fred Hutchinson Cancer Research Center; US PHS
[R01 CA98285, R01 CA064277, R01 CA90899]; Vanderbilt University;
National Health and Medical Research Council of Australia [339435];
Cancer Council Queensland [4196615]; Cancer Council Tasmania [403031,
457636]; Cancer Research UK [C490/A10124]; National Health and Medical
Research Council [552402]; Medical Research Council [G0000934]; Wellcome
Trust [068545/Z/02, 085475]; National Health and Medical Research
Council of Australia (NHMRC); University of Newcastle; Gladys M Brawn
Senior Research Fellowship scheme; Vincent Fairfax Family Foundation;
Hunter Medical Research Institute; Hunter Area Pathology Service;
National Health and Medical Research Council (NHMRC); Joseph Mitchell
Trust; California Breast Cancer Research Fund [97-10500]; NCI; National
Cancer Institute of Canada; Canadian Cancer Society; Canadian Institute
for Health Research; Alberta Innovates-Health Solutions; Alberta Cancer
Foundation through the Weekend to End Women's Cancers Breast Cancer
Chair; Canada Research Chairs program; Italian Association for Research
on Cancer (AIRC); Ricerca Finalizzata Regione Piemonte
FX The Nurses' Health Study (NHS) is supported by the NCI, NIH Grants
Number 1R01 CA134958, 2R01 CA082838, P01 CA087969, and R01 CA49449. The
authors would like to thank the participants and staff of the Nurses'
Health Study for their valuable contributions as well as the following
state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL,
GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH,
OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. In addition, this study was
approved by the Connecticut Department of Public Health (DPH) Human
Investigations Committee. Certain data used in this publication were
obtained from the DPH. The authors assume full responsibility for
analyses and interpretation of these data. The authors would also like
to thank Channing Division of Network Medicine, Department of Medicine,
Brigham and Women's Hospital and Harvard Medical School. Finally, the
authors would also like to acknowledge Pati Soule and Hardeep Ranu for
their laboratory assistance.; The Cancer Prevention Study II (CPS-II)
cohort is supported by the American Cancer Society (ACS) and by NCI, NIH
Grant Number 2R01 CA082838. The CPS-II would like to thank the CPS-II
participants and Study Management Group for their invaluable
contributions to this research. The authors would also like to
acknowledge the contribution to this study from central cancer
registries supported through the Centers for Disease Control and
Prevention National Program of Cancer Registries, and cancer registries
supported by the National Cancer Institute Surveillance Epidemiology and
End Results program.; The Multiethnic Cohort Study (MEC) is supported by
the NCI, NHI Grants Number CA54281, CA128008 and 2R01 CA082838.; The
Fred Hutchinson Cancer Research Center (FHCRC) is supported by NCI, NIH
Grant Number 2R01 CA082838, NIH RO1 CA105212, RO1 CA 87538, RO1 CA75977,
RO3 CA80636, NO1 HD23166, R35 CA39779, KO5 CA92002 and funds from the
Fred Hutchinson Cancer Research Center.; The Women's Insights and Shared
Experiences (WISE) is supported by the NCI, NIH Grants Number
P01-CA77596 and 2R01 CA082838.; The Connecticut Endometrial Cancer Study
is supported by NCI, NIH Grant Number 2R01 CA082838.; The Shanghai
Endometrial Cancer Genetic Study (SECGS) was supported by the US PHS
grants R01 CA98285, R01 CA064277, and R01 CA90899, NCI, NIH Grant Number
2R01 CA082838 as well as institutional funds from the Vanderbilt
University. The SECGS would like to thank research staff and
participants of the Shanghai Endometrial Cancer Study and Shanghai
Breast Cancer Study for their contributions in the study.; The EDGE
Study (Estrogen, Diet, Genetics, and Endometrial Cancer) is supported by
NCI, NIH Grants Number 2R01 CA082838, R01CA83918 (Olson PI) and
P30-CA008748 (Cancer Center Support Grant).; The Australian National
Endometrial Cancer Study (ANECS) recruitment was supported by project
grants from the National Health and Medical Research Council of
Australia (ID#339435), The Cancer Council Queensland (ID#4196615) and
Cancer Council Tasmania (ID#403031 and ID#457636). The Studies of
Epidemiology and Risk factors in Cancer Heredity (SEARCH) recruitment
was funded by a program grant from Cancer Research UK [C490/A10124].
Case genotyping was supported by the National Health and Medical
Research Council (ID#552402). Control data was generated by the Wellcome
Trust Case Control Consortium (WTCCC), and a full list of the
investigators who contributed to the generation of the data is available
from the WTCCC website. We acknowledge use of DNA from the British 1958
Birth Cohort collection, funded by the Medical Research Council grant
G0000934 and the Wellcome Trust grant 068545/Z/02. Funding for this
project was provided by the Wellcome Trust under award 085475.
Recruitment of the QIMR controls was supported by the National Health
and Medical Research Council of Australia (NHMRC). The University of
Newcastle, the Gladys M Brawn Senior Research Fellowship scheme, The
Vincent Fairfax Family Foundation, the Hunter Medical Research Institute
and the Hunter Area Pathology Service all contributed towards the costs
of establishing the Hunter Community Study. A.B.S. is supported by the
National Health and Medical Research Council (NHMRC) Fellowship Scheme.
D.F.E. is a Principal Research Fellow of Cancer Research UK. A.M.D is
supported by the Joseph Mitchell Trust. ANECS, SEARCH, QIMR and the HCS
thank the many individuals who participated in the research studies,
Penny Webb, Kaltin Ferguson, and the ANECS research team, Nick Martin,
Grant Montgomery, Dale Nyholt and Anjali Henders for access to GWAS data
from QIMR controls, Paul Pharoah for his role in implementing and
supporting the SEARCH study, the Eastern Cancer Registration and
Information Centre and the SEARCH research team, the numerous
institutions and their staff who supported recruitment, and acknowledge
the contribution of our clinical and scientific collaborators and their
staff. See http://www.anecs.org.au/ for full listing of the ANECS Group
and other contributors to ANECS. SEARCH collaborators include Caroline
Baynes, Don Conroy, Bridget Curzon, Patricia Harrington, Sue Irvine,
Clare Jordan, Craig Luccarini, Rebecca Mayes, Hannah Munday, Barbara
Perkins, Radka Platte, Anabel Simpson, Anne Stafford and Judy West. QIMR
thanks Margie Wright, Lisa Bowdler, Sara Smith, Megan Campbell and Scott
Gordon for control sample collection and data processing.; The
California Teachers Study (CTS) is supported by NCI, NIH Grant Number
2R01 CA082838, R01 CA91019 and R01 CA77398, and contract 97-10500 from
the California Breast Cancer Research Fund.; The Polish Endometrial
Cancer Study (PECS) is supported by the Intramural Research Program of
the NCI.; The Prostate, Lung, Colorectal, and Ovarian Cancer Screening
Trial (PLCO) is supported by the Extramural and the Intramural Research
Programs of the NCI.; The Alberta Health Services Study (AHS) was
supported by operating grants obtained from the National Cancer
Institute of Canada with funds from the Canadian Cancer Society and the
Canadian Institute for Health Research. The AHS is also supported by
NCI, NIH Grant Number 2R01 CA082838. Dr Christine Friedenreich is
supported by career awards from Alberta Innovates-Health Solutions and
the Alberta Cancer Foundation through the Weekend to End Women's Cancers
Breast Cancer Chair. Dr Linda Cook was supported through the Canada
Research Chairs program.; The Turin endometrial cancer case control
study was supported by the Italian Association for Research on Cancer
(AIRC) and Ricerca Finalizzata Regione Piemonte.
NR 43
TC 16
Z9 17
U1 1
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-6717
EI 1432-1203
J9 HUM GENET
JI Hum. Genet.
PD FEB
PY 2014
VL 133
IS 2
BP 211
EP 224
DI 10.1007/s00439-013-1369-1
PG 14
WC Genetics & Heredity
SC Genetics & Heredity
GA 288ZY
UT WOS:000329652000008
PM 24096698
ER
PT J
AU Bearman, G
Bryant, K
Leekha, S
Mayer, J
Munoz-Price, LS
Murthy, R
Palmore, T
Rupp, ME
White, J
AF Bearman, Gonzalo
Bryant, Kristina
Leekha, Surbhi
Mayer, Jeanmarie
Munoz-Price, L. Silvia
Murthy, Rekha
Palmore, Tara
Rupp, Mark E.
White, Joshua
TI Healthcare Personnel Attire in Non-Operating-Room Settings
SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY
LA English
DT Article
ID PHYSICIAN ATTIRE; WHITE COATS; BACTERIAL-CONTAMINATION; PATIENTS
PREFERENCE; PATIENT ATTITUDES; HOSPITAL DOCTORS; WORKERS UNIFORMS;
CROSSOVER TRIAL; SCRUBS; POLICY
AB Healthcare personnel (HCP) attire is an aspect of the medical profession steeped in culture and tradition. The role of attire in cross-transmission remains poorly established, and until more definitive information exists priority should be placed on evidence-based measures to prevent healthcare-associated infections (HAIs). This article aims to provide general guidance to the medical community regarding HCP attire outside the operating room. In addition to the initial guidance statement, the article has 3 major components: (1) a review and interpretation of the medical literature regarding (a) perceptions of HCP attire (from both HCP and patients) and (b) evidence for contamination of attire and its potential contribution to cross-transmission; (2) a review of hospital policies related to HCP attire, as submitted by members of the Society for Healthcare Epidemiology of America (SHEA) Guidelines Committee; and (3) a survey of SHEA and SHEA Research Network members that assessed both institutional HCP attire policies and perceptions of HCP attire in the cross-transmission of pathogens. Recommendations for HCP attire should attempt to balance professional appearance, comfort, and practicality with the potential role of apparel in the cross-transmission of pathogens. Although the optimal choice of HCP attire for inpatient care remains undefined, we provide recommendations on the use of white coats, neckties, footwear, the bare-below-the-elbows strategy, and laundering. Institutions considering these optional measures should introduce them with a well-organized communication and education effort directed at both HCP and patients. Appropriately designed studies are needed to better define the relationship between HCP attire and HAIs.
C1 [Bearman, Gonzalo; White, Joshua] Virginia Commonwealth Univ, Richmond, VA 23298 USA.
[Bryant, Kristina] Univ Louisville, Louisville, KY 40292 USA.
[Leekha, Surbhi] Univ Maryland, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Mayer, Jeanmarie] Univ Utah, Sch Med, Dept Internal Med, Div Infect Dis, Salt Lake City, UT USA.
[Munoz-Price, L. Silvia] Univ Miami, Dept Med, Miami, FL USA.
[Munoz-Price, L. Silvia] Univ Miami, Dept Publ Hlth Sci, Miami, FL USA.
[Murthy, Rekha] Cedars Sinai Med Ctr, Dept Hosp Epidemiol, Los Angeles, CA 90048 USA.
[Palmore, Tara] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Rupp, Mark E.] Univ Nebraska Med Ctr, Omaha, NE USA.
RP Bearman, G (reprint author), Virginia Commonwealth Univ, Med Coll Virginia Campus, Richmond, VA 23298 USA.
EM gbearman@mcvh-vcu.edu
FU SHEA Research Network; Pfizer; Cardinal Health; BioVigil; Vestagen
Technical Textiles; 3M
FX Financial support. This study was supported in part by the SHEA Research
Network.; Potential conflicts of interest. G.B. reports receiving grants
from Pfizer, Cardinal Health, BioVigil, and Vestagen Technical Textiles.
M.E.R. reports receiving research grants/contracts from 3M and having an
advisory/consultant role with 3M, Ariste, Care Fusion, and Molnlycke.
All other authors report no conflicts of interest relevant to this
article.
NR 59
TC 23
Z9 23
U1 0
U2 12
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0899-823X
EI 1559-6834
J9 INFECT CONT HOSP EP
JI Infect. Control Hosp. Epidemiol.
PD FEB 1
PY 2014
VL 35
IS 2
BP 107
EP 121
DI 10.1086/675066
PG 15
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 292AC
UT WOS:000329873000001
PM 24442071
ER
PT J
AU Decker, BK
Palmore, TN
AF Decker, Brooke K.
Palmore, Tara N.
TI Waterborne Pathogen Detection: More than Just "Location, Location,
Location ... "
SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY
LA English
DT Editorial Material
ID NON-TOUCH FITTINGS; PSEUDOMONAS-AERUGINOSA; LEGIONNAIRES-DISEASE;
OUTBREAK; COLONIZATION; INFECTIONS; HOSPITALS; AERATORS; RISK
C1 [Decker, Brooke K.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
[Palmore, Tara N.] NIAID, Bethesda, MD 20892 USA.
[Palmore, Tara N.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
RP Palmore, TN (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM tpalmore@mail.nih.gov
OI Decker M.D., Brooke K/0000-0002-3404-9115
NR 15
TC 4
Z9 4
U1 0
U2 4
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0899-823X
EI 1559-6834
J9 INFECT CONT HOSP EP
JI Infect. Control Hosp. Epidemiol.
PD FEB 1
PY 2014
VL 35
IS 2
BP 130
EP 131
DI 10.1086/675067
PG 2
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 292AC
UT WOS:000329873000003
PM 24442073
ER
PT J
AU Saver, JL
Starkman, S
Eckstein, M
Stratton, S
Pratt, F
Hamilton, S
Conwit, R
Liebeskind, DS
Sung, G
Sanossian, N
AF Saver, Jeffrey L.
Starkman, Sidney
Eckstein, Marc
Stratton, Samuel
Pratt, Frank
Hamilton, Scott
Conwit, Robin
Liebeskind, David S.
Sung, Gene
Sanossian, Nerses
CA FAST-MAG Investigators Coordinator
TI Methodology of the Field Administration of Stroke Therapy - Magnesium
(FAST-MAG) phase 3 trial: Part 1-rationale and general methods
SO INTERNATIONAL JOURNAL OF STROKE
LA English
DT Article
DE ambulance; clinical trial; magnesium; neuroprotection; paramedic;
prehospital
ID ACUTE ISCHEMIC-STROKE; RANDOMIZED CLINICAL-TRIAL; ENDOVASCULAR
TREATMENT; TRENDS
AB RationalePrehospital initiation by paramedics may enable delivery of neuroprotective therapies to stroke patients in the hyperacute period when they are most effective in preclinical studies. Magnesium is neuroprotective in experimental stroke models and has been shown to be safe with signals of potential efficacy when started early after onset of human cerebral ischemia.
Aims(a) To demonstrate that paramedic initiation of the neuroprotective agent magnesium sulfate in the field is an efficacious and safe treatment for acute stroke; (b) To demonstrate that field enrollment of acute stroke patients is a practical and feasible strategy for phase 3 stroke trials, permitting enrollment of greater numbers of patients in hyperacute time windows.
DesignMulticenter, randomized, double-blinded, placebo-controlled, pivotal clinical trial.
Study ProceduresThe study is enrolling 1700 patients (850 in each arm) with likely acute stroke, including both cerebral infarction and intracerebral hemorrhage patients. Inclusion criteria are: (a) likely stroke as identified by the modified Los Angeles Prehospital Stroke Screen (mLAPSS), (b) age 40-95, (c) symptom onset within 2h of treatment initiation, and (d) deficit present 15min. Paramedics administer a loading dose of magnesium sulfate (Mg) or matched placebo in the field, 4 grams over 15min. In the Emergency Department, a maintenance infusion follows, 16 grams Mg or matched placebo over 24h.
OutcomesThe primary endpoint is the modified Rankin Scale measure of global disability, assessed using the Rankin Focused Assessment, 90 days after treatment. Secondary efficacy endpoints include the NIHSS (neurologic deficit), Barthel Index (activities of daily living), and the Stroke Impact Scale (quality of life).
C1 [Saver, Jeffrey L.; Starkman, Sidney; Liebeskind, David S.] Univ Calif Los Angeles, David Geffen Sch Med, Comprehens Stroke Ctr, Los Angeles, CA 90095 USA.
[Saver, Jeffrey L.; Starkman, Sidney; Liebeskind, David S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA.
[Starkman, Sidney; Pratt, Frank] Univ Calif Los Angeles, David Geffen Sch Med, Dept Emergency Med, Los Angeles, CA 90095 USA.
[Eckstein, Marc] Univ So Calif, Keck Sch Med, Dept Emergency Med, Los Angeles Fire Dept, Los Angeles, CA 90033 USA.
[Stratton, Samuel] Harbor UCLA Med Ctr, Dept Emergency Med, Los Angeles EMS Agcy, Orange Cty EMS Agcy, Los Angeles, CA USA.
[Pratt, Frank] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles Cty Fire EMS Agcy, Los Angeles, CA 90095 USA.
[Hamilton, Scott] Stanford Univ, Palo Alto, CA 94304 USA.
[Conwit, Robin] NINDS, Bethesda, MD 20892 USA.
[Sung, Gene; Sanossian, Nerses] Univ So Calif, Keck Sch Med, Dept Neurol, Los Angeles, CA 90033 USA.
RP Saver, JL (reprint author), UCLA Comprehens Stroke Ctr, 710 Westwood Plaza, Los Angeles, CA 90095 USA.
EM jsaver@mednet.ucla.edu
OI Saver, Jeffrey/0000-0001-9141-2251
FU National Institute of Neurological Diseases and Stroke (NINDS) [U01
NS44364]
FX This study is funded by the National Institute of Neurological Diseases
and Stroke (NINDS) # U01 NS44364.
NR 22
TC 18
Z9 18
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1747-4930
EI 1747-4949
J9 INT J STROKE
JI Int. J. Stroke
PD FEB
PY 2014
VL 9
IS 2
BP 215
EP 219
DI 10.1111/ijs.12243
PG 5
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 291LH
UT WOS:000329829700015
PM 24444116
ER
PT J
AU Saver, JL
Starkman, S
Eckstein, M
Stratton, S
Pratt, F
Hamilton, S
Conwit, R
Liebeskind, DS
Sung, G
Sanossian, N
AF Saver, Jeffrey L.
Starkman, Sidney
Eckstein, Marc
Stratton, Samuel
Pratt, Frank
Hamilton, Scott
Conwit, Robin
Liebeskind, David S.
Sung, Gene
Sanossian, Nerses
CA FAST-MAG Investigators Coordinator
TI Methodology of the Field Administration of Stroke Therapy - Magnesium
(FAST-MAG) phase 3 trial: Part 2-prehospital study methods
SO INTERNATIONAL JOURNAL OF STROKE
LA English
DT Article
DE ambulance; clinical trial; magnesium; neuroprotection; paramedic;
prehospital
ID EXPLICIT INFORMED-CONSENT; HOSPITAL CARDIAC-ARREST; CLINICAL-TRIAL;
ELICITATION; DIAZEPAM
AB RationaleIn acute stroke, the volume of salvageable brain tissue is maximal at onset and declines rapidly with time. Prehospital start of clinical trial interventions would enable delivery of neuroprotective agents, such as magnesium sulfate, to stroke patients in the hyperacute period when they are potentially most effective.
AimsA broad aim of the FAST-MAG study is to develop and validate techniques to perform pivotal trials of neuroprotective therapies for acute stroke in the prehospital setting. In tandem with an accompanying general trial design article, this manuscript provides a detailed overview of several novel prehospital study methods employed in the NIH FAST-MAG Trial.
DesignMulticenter, randomized, double-blinded, placebo-controlled, pivotal clinical trial. Special Prehospital Procedures Distinctive prehospital methods deployed in FAST-MAG include: identifying likely stroke patients using the Los Angeles Prehospital Stroke Screen; eliciting explicit informed consent from patients or on scene legally authorized representatives via cellphone discussion with off-scene physicians; paramedic rating of pretreatment stroke severity using the Los Angeles Motor Scale; assigning patients to a study arm using blinded, pre-encounter randomization; facilitating continuity of study infusion from the field to the ED by stocking ambulances with study kits including both field and hospital doses; and electronic fax consent signature documentation by geographically separated subjects and enrolling physicians.
DiscussionThe suite of prehospital trial methods developed for the FAST-MAG Trial enable enrollment of patients in very early time windows, including the hyperacute, golden hour' period immediately after stroke onset.
C1 [Saver, Jeffrey L.; Starkman, Sidney; Liebeskind, David S.] Univ Calif Los Angeles, David Geffen Sch Med, Comprehens Stroke Ctr, Los Angeles, CA 90095 USA.
[Saver, Jeffrey L.; Liebeskind, David S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA.
[Starkman, Sidney; Pratt, Frank] Univ Calif Los Angeles, David Geffen Sch Med, Dept Emergency Med, Los Angeles, CA 90095 USA.
[Starkman, Sidney] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA.
[Eckstein, Marc] Univ So Calif, Keck Sch Med, Dept Emergency Med, Los Angeles Fire Dept, Los Angeles, CA 90033 USA.
[Stratton, Samuel] Harbor UCLA Med Ctr, Orange Cty EMS Agcy, Los Angeles EMS Agcy, Dept Emergency Med, Los Angeles, CA USA.
[Pratt, Frank] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles Cty Fire EMS Agcy, Los Angeles, CA 90095 USA.
[Hamilton, Scott] Stanford Univ, Palo Alto, CA 94304 USA.
[Conwit, Robin] NINDS, Bethesda, MD 20892 USA.
[Sung, Gene; Sanossian, Nerses] Univ So Calif, Keck Sch Med, Dept Neurol, Los Angeles, CA 90033 USA.
RP Saver, JL (reprint author), UCLA Comprehens Stroke Ctr, 710 Westwood Plaza, Los Angeles, CA 90095 USA.
EM jsaver@mednet.ucla.edu
RI Emchi, Karma/Q-1952-2016;
OI Saver, Jeffrey/0000-0001-9141-2251
FU NINDS NIH HHS [U01 NS044364]
NR 10
TC 19
Z9 21
U1 0
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1747-4930
EI 1747-4949
J9 INT J STROKE
JI Int. J. Stroke
PD FEB
PY 2014
VL 9
IS 2
BP 220
EP 225
DI 10.1111/ijs.12242
PG 6
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 291LH
UT WOS:000329829700016
PM 24444117
ER
PT J
AU Bruno, A
Durkalski, VL
Hall, CE
Juneja, R
Barsan, WG
Janis, S
Meurer, WJ
Fansler, A
Johnston, KC
AF Bruno, Askiel
Durkalski, Valerie L.
Hall, Christiana E.
Juneja, Rattan
Barsan, William G.
Janis, Scott
Meurer, William J.
Fansler, Amy
Johnston, Karen C.
CA SHINE Investigators
TI The Stroke Hyperglycemia Insulin Network Effort (SHINE) trial protocol:
a randomized, blinded, efficacy trial of standard vs. intensive
hyperglycemia management in acute stroke
SO INTERNATIONAL JOURNAL OF STROKE
LA English
DT Article
DE acute ischemic stroke; cerebral infarction; clinical trial;
hyperglycemia; protocols
ID ACUTE ISCHEMIC-STROKE; BLOOD-GLUCOSE; CLINICAL-TRIALS; PILOT TRIAL;
MORTALITY; INTERVENTION; HYPOGLYCEMIA; ASSOCIATION; INFARCTION; OUTCOMES
AB Rationale Patients with acute ischemic stroke and hyperglycemia have worse outcomes than those without hyperglycemia. Intensive glucose control during acute stroke is feasible and can be accomplished safely but has not been fully assessed for efficacy.
Aims The Stroke Hyperglycemia Insulin Network Effort trial aims to determine the safety and efficacy of standard vs. intensive glucose control with insulin in hyperglycemic acute ischemic stroke patients.
Design This is a randomized, blinded, multicenter, phase III trial of approximately 1400 hyperglycemic patients who receive either standard sliding scale subcutaneous insulin (blood glucose range 80-179 mg/dL, 4.44-9.93 mmol/L) or continuous intravenous insulin (target blood glucose 80-130mg/dL, 444-721mmol/L) for up to 72 h, starting within 12 h of stroke symptom onset. The acute treatment phase is single blind (for the patients), but the final outcome assessment is double blind. The study is powered to detect a 7% absolute difference in favorable outcome at 90 days.
Study outcomes The primary outcome is a baseline severity adjusted 90-day modified Rankin Scale score, defined as 0, 0-1, or 0-2, if the baseline National Institutes of Health Stroke Scale score is 3-7, 8-14, or 15-22, respectively. The primary safety outcome is the rate of severe hypoglycemia (< 40 mg/dL, < 2.22 mmol/L).
Discussion This trial will provide important novel information about preferred management of acute ischemic stroke patients with hyperglycemia. It will determine the potential benefits and risks of intensive glucose control during acute stroke.
C1 [Bruno, Askiel] Med Coll Georgia, Dept Neurol, Augusta, GA 30912 USA.
[Durkalski, Valerie L.] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA.
[Hall, Christiana E.] Univ Texas SW Med Ctr Dallas, Dept Neurol & Neurotherapeut, Dallas, TX 75390 USA.
[Juneja, Rattan] Indiana Univ Sch Med, Div Endocrinol, Dept Med, Indianapolis, IN 46202 USA.
[Barsan, William G.; Meurer, William J.] Univ Michigan, Dept Emergency Med, Ann Arbor, MI 48109 USA.
[Janis, Scott] NINDS, NIH, Bethesda, MD 20892 USA.
[Fansler, Amy; Johnston, Karen C.] Univ Virginia, Sch Med, Dept Neurol, Charlottesville, VA 22908 USA.
RP Bruno, A (reprint author), Med Coll Georgia, Dept Neurol, BI 3076, Augusta, GA 30912 USA.
EM abruno@georgiahealth.edu
FU NIH/NINDS [U01-NS069498, U01-NS056975, U01-NS059041]
FX The SHINE trial is funded by an NIH/NINDS grant U01-NS069498 and
registered at ClinicalTrials.gov, #NCT01369069. The NETT Clinical
Coordinating Center is funded by the NIH/NINDS grant U01-NS056975. The
NETT Statistical and Data Management Center is funded by the NIH/NINDS
grant U01-NS059041.
NR 29
TC 21
Z9 22
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1747-4930
EI 1747-4949
J9 INT J STROKE
JI Int. J. Stroke
PD FEB
PY 2014
VL 9
IS 2
BP 246
EP 251
DI 10.1111/ijs.12045
PG 6
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 291LH
UT WOS:000329829700020
PM 23506245
ER
PT J
AU Nociti, FH
Foster, BL
Tran, AB
Dunn, D
Presland, RB
Wang, L
Bhattacharyya, N
Collins, MT
Somerman, MJ
AF Nociti, F. H., Jr.
Foster, B. L.
Tran, A. B.
Dunn, D.
Presland, R. B.
Wang, L.
Bhattacharyya, N.
Collins, M. T.
Somerman, M. J.
TI Vitamin D Represses Dentin Matrix Protein 1 in Cementoblasts and
Osteocytes
SO JOURNAL OF DENTAL RESEARCH
LA English
DT Article
DE Vitamin D receptor; phosphate homeostasis; osteogenesis; SIBLING family;
fibroblast growth factor 23; phosphate regulating endopeptidase homolog
ID GENE-EXPRESSION; PULP CELLS; PTHRP GENE; D-RECEPTOR; PHOSPHATE; FGF23;
BONE; PHEX; ESTABLISHMENT; TRANSCRIPTION
AB Calcium and phosphorus homeostasis is achieved by interplay among hormones, including 1,25(OH)(2)D-3 (1,25D), parathyroid hormone, and fibroblast growth factor 23 (FGF23), and their interactions with other proteins. For example, mutations in dentin matrix protein 1 (DMP-1) result in increased FGF23 and hypophosphatemic rickets. 1,25D is reported to modulate FGF23; thus, we hypothesized that 1,25D may be involved in modulating DMP-1 in an intermediary step. Murine cementoblasts (OCCM-30) and osteocyte-like cells (MLO-Y4 and MLO-A5), known to express DMP-1, were used to analyze effects of 1,25D on DMP-1 expression in vitro. DMP-1 mRNA levels decreased by 50% (p < .05) in the presence of 1,25D in all cell types, while use of a vitamin D receptor (VDR) agonist (EB1089) and antagonist (23S,25S)-DLAM-2P confirmed that VDR pathway activation was required for this response. Further analysis showed that histone deacetylase recruitment was necessary, but neither protein kinase A nor C pathways were required. In conclusion, our results support the hypothesis that 1,25D regulates DMP-1 expression through a VDR-dependent mechanism, possibly contributing to local changes in bone/tooth mineral homeostasis.
C1 [Nociti, F. H., Jr.; Foster, B. L.; Tran, A. B.; Wang, L.; Somerman, M. J.] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Nociti, F. H., Jr.] Univ Estadual Campinas, Piracicaba Dent Sch, Dept Prosthodont & Periodont, Sao Paulo, Brazil.
[Dunn, D.] Univ Washington, Sch Dent, Dept Periodont, Seattle, WA 98195 USA.
[Presland, R. B.] Univ Washington, Sch Dent, Dept Oral Hlth Sci, Seattle, WA 98195 USA.
[Bhattacharyya, N.; Collins, M. T.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA.
RP Somerman, MJ (reprint author), NIAMSD, NIH, Bethesda, MD 20892 USA.
EM Martha.somerman@nih.gov
RI Nociti, Francisco/G-4907-2015; Foster, Brian/H-8375-2015;
OI Foster, Brian/0000-0003-3444-0576; Presland, Richard/0000-0003-1440-7402
FU Intramural Research Programs of the National Institute of Arthritis and
Musculoskeletal and Skin Diseases; National Institute of Dental and
Craniofacial Research
FX This research was supported by the Intramural Research Programs of the
National Institute of Arthritis and Musculoskeletal and Skin Diseases
(MJS) and the National Institute of Dental and Craniofacial Research
(MTC). The authors declare no potential conflicts of interest with
respect to the authorship and/or publication of this article. The
authors thank Dr. Lynda Bonewald (University of Missouri-Kansas City)
for providing MLO-Y4 and MLO-A5 cells, Dr. Kazuo Nagasawa (Tokyo
University of Agriculture and Technology) for providing vitamin D
receptor antagonist, Dr. Jian Feng (Baylor College of Dentistry) for
providing DMP-1 promoter constructs, and Dr. Chunlin Qin (Baylor College
of Dentistry) for providing DMP-1 antibody.
NR 30
TC 9
Z9 10
U1 0
U2 11
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0022-0345
EI 1544-0591
J9 J DENT RES
JI J. Dent. Res.
PD FEB
PY 2014
VL 93
IS 2
BP 148
EP 154
DI 10.1177/0022034513516344
PG 7
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 290QT
UT WOS:000329774100006
PM 24334408
ER
PT J
AU Zhang, Y
Song, Y
Ravindran, S
Gao, Q
Huang, CC
Ramachandran, A
Kulkarni, A
George, A
AF Zhang, Y.
Song, Y.
Ravindran, S.
Gao, Q.
Huang, C. C.
Ramachandran, A.
Kulkarni, A.
George, A.
TI DSPP Contains an IRES Element Responsible for the Translation of Dentin
Phosphophoryn
SO JOURNAL OF DENTAL RESEARCH
LA English
DT Article
DE extracellular matrix (ECM); cell biology; cell differentiation; dentin;
matrix biology; odontoblast(s)
ID SIALOPHOSPHOPROTEIN DSPP; CLEAVAGE SITE; IN-VITRO; SIALOPROTEIN;
PHOSPHOPROTEIN; INITIATION; PRODUCTS; PROTEINS; REGION; CELLS
AB The major phosphoprotein in dentin is the aspartic acid and serine-rich protein called dentin phosphophoryn (DPP). DPP appears to be synthesized as a part of a larger compound protein, dentin sialophosphoprotein (DSPP). DSPP has never been isolated or detected in dentin extracts. It is now evident that DSPP is a chimeric protein composed of 3 parts: dentin sialoprotein (DSP), DPP, and dentin glycoprotein (DGP). Previous reports have suggested that the BMP1 protease is responsible for processing DSPP. However, unequal amounts of these products are present in the dentin matrix. Here, we provide evidence for an internal ribosome entry site in the DSPP gene that directs the synthesis of DPP. This mechanism would account for unequal amounts of intracellular DSP and DPP. The internal ribosomal entry site (IRES) activity varied in different cell types, suggesting the presence of additional regulatory elements during the translational regulation of DPP. Further, we provide evidence that DPP is transported to the extracellular matrix (ECM) through exosomes. Using tissue recombination and lentivirus-mediated gain-of-function approaches, we also demonstrate that DPP is essential for the formation of well-defined tooth structures with mineralized dentin matrix.
C1 [Zhang, Y.; Song, Y.; Ravindran, S.; Gao, Q.; Huang, C. C.; Ramachandran, A.; George, A.] Univ Illinois, Dept Oral Biol, Brodie Tooth Dev Genet & Regenerat Med Res Lab, Chicago, IL 60612 USA.
[Kulkarni, A.] NIDCR, NIH, Bethesda, MD USA.
RP George, A (reprint author), Univ Illinois, Dept Oral Biol, Brodie Tooth Dev Genet & Regenerat Med Res Lab, Chicago, IL 60612 USA.
EM anneg@uic.edu
OI GEORGE, ANNE/0000-0002-9008-7642
FU National Institute of Dental and Craniofacial Research, National
Institutes of Health, US Department of Health and Human Services [R01 DE
19633]; Brodie Endowment Fund
FX The authors thank Dr. Karthikeyan Narayanan (IBN, Singapore) for useful
discussions. This work was supported by the National Institute of Dental
and Craniofacial Research, National Institutes of Health, US Department
of Health and Human Services (R01 DE 19633), and by the Brodie Endowment
Fund. The authors declare no potential conflicts of interest with
respect to the authorship and/or publications of this article.
NR 26
TC 7
Z9 7
U1 0
U2 7
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0022-0345
EI 1544-0591
J9 J DENT RES
JI J. Dent. Res.
PD FEB
PY 2014
VL 93
IS 2
BP 155
EP 161
DI 10.1177/0022034513516631
PG 7
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 290QT
UT WOS:000329774100007
PM 24352500
ER
PT J
AU Abou-Alfa, GK
Capanu, M
O'Reilly, EM
Ma, J
Chou, JF
Gansukh, B
Shia, J
Kalin, M
Katz, S
Abad, L
Reidy-Lagunes, DL
Kelsen, DP
Chen, HX
Saltz, LB
AF Abou-Alfa, Ghassan K.
Capanu, Marinela
O'Reilly, Eileen M.
Ma, Jennifer
Chou, Joanne F.
Gansukh, Bolorsukh
Shia, Jinru
Kalin, Marcia
Katz, Seth
Abad, Leslie
Reidy-Lagunes, Diane L.
Kelsen, David P.
Chen, Helen X.
Saltz, Leonard B.
TI A phase II study of cixutumumab (IMC-A12, NSC742460) in advanced
hepatocellular carcinoma
SO JOURNAL OF HEPATOLOGY
LA English
DT Article
DE Cixutumumab (IMC-A12, NSC742460); Hepatocellular Carcinoma; IGF-IR; Free
IGF1; IGF2; IGFBP 1; IGFBP 3; Diabetes
ID GROWTH-FACTOR RECEPTOR; LIVER-CIRRHOSIS; IN-VIVO; TUMORS; ACTIVATION;
ANTIBODY; CELLS
AB Background & Aims: IGF-IR is implicated in hepatic carcinogenesis. This and preliminary evidence of biological activity of anti-IGF-1R monoclonal antibody cixutumumab in phase I trials prompted this phase II study.
Methods: Patients with advanced HCC, Child-Pugh A-B8, received cixutumumab 6 mg/kg weekly, in a Simon two-stage design study, with the primary endpoints being 4-month PFS and RECIST-defined response rate. Tissue and circulating markers plus different HCC scoring systems were evaluated for correlation with PFS and OS.
Results: As a result of pre-specified futility criteria, only stage 1 was accrued: N = 24: median age 67.5 years (range 49-83), KPS 80% (70-90%), 20 males (83%), 9 stage III (37%)/15 stage IV (63%), 18 Child-Pugh A (75%), 11 HBV (46%)/10 HCV (42%)/11 alcoholic cirrhosis (46%)/2 NASH (8%), 11 (46%) diabetic. Median number of doses: 7 (range 1-140). Grade 3/4 toxicities > 10% included: diabetes, elevated liver function tests, hyponatremia, and lymphopenia. Four-month PFS was 30% (95% CI 13-48), and there were no objective responses. Median overall survival was 8 months (95% CI 5.8-14). IGF-R1 staining did not correlate with outcome. Elevated IGFBP-1 correlated with improved PFS (1.2 [95% CI 1-1.4]; p 0.009) and OS (1.2 [95% CI 1.1-1.4]; p 0.003).
Conclusions: Cixutumumab monotherapy did not have clinically meaningful activity in this unselected HCC population. Grade 3-4 hyperglycemia occurred in 46% of patients. Elevated IGFBP-1 correlated with improved PFS and OS. (C) 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
C1 [Abou-Alfa, Ghassan K.; O'Reilly, Eileen M.; Ma, Jennifer; Gansukh, Bolorsukh; Kalin, Marcia; Reidy-Lagunes, Diane L.; Kelsen, David P.; Saltz, Leonard B.] Mem Sloan Kettering Canc Ctr, Dept Internal Med, New York, NY 10065 USA.
[Abou-Alfa, Ghassan K.; O'Reilly, Eileen M.; Reidy-Lagunes, Diane L.; Kelsen, David P.; Saltz, Leonard B.] Cornell Univ, Weill Med Coll, Dept Internal Med, New York, NY 10021 USA.
[Capanu, Marinela; Chou, Joanne F.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA.
[Shia, Jinru] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA.
[Katz, Seth] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10065 USA.
[Abad, Leslie] ImClone Syst, Res Dept, New York, NY USA.
[Chen, Helen X.] NCI, CTEP, Bethesda, MD 20892 USA.
RP Abou-Alfa, GK (reprint author), Mem Sloan Kettering Canc Ctr, 300 East 66th St, New York, NY 10065 USA.
EM abou-alg@mskcc.org
OI Katz, Seth/0000-0001-8941-950X; Shia, Jinru/0000-0002-4351-2511; Saltz,
Leonard/0000-0001-8353-4670
FU NCI phase II grant [NO1-CM62206]; ImClone Systems
FX This study was supported by NCI phase II grant NO1-CM62206. The
correlative studies were supported by a research grant from ImClone
Systems.
NR 23
TC 28
Z9 31
U1 1
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
EI 1600-0641
J9 J HEPATOL
JI J. Hepatol.
PD FEB
PY 2014
VL 60
IS 2
BP 319
EP 324
PG 6
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 291UJ
UT WOS:000329855600014
PM 24045151
ER
PT J
AU Qu, AJ
Jiang, CT
Cai, Y
Kim, JH
Tanaka, N
Ward, JM
Shah, YM
Gonzalez, FJ
AF Qu, Aijuan
Jiang, Changtao
Cai, Yan
Kim, Jung-Hwan
Tanaka, Naoki
Ward, Jerrold M.
Shah, Yatrik M.
Gonzalez, Frank J.
TI Role of Myc in hepatocellular proliferation and hepatocarcinogenesis
SO JOURNAL OF HEPATOLOGY
LA English
DT Article
DE Myc; Cell proliferation; Tumorigenesis; BrdU; Cell cycle control
ID C-MYC; PEROXISOME PROLIFERATORS; GROWTH-FACTOR; PPAR-ALPHA; CELL-CYCLE;
DNA-REPLICATION; MOUSE MODEL; LIVER; CANCER; GENE
AB Background & Aims: Myc is involved in cell growth, proliferation, apoptosis, energy metabolism, and differentiation. Whether it is essential for hepatocellular proliferation and carcinogenesis is unclear due to a lack of an efficient hepatocyte-specific Myc disruption model. This study used a novel genetic model to investigate the involvement of Myc in hepatocellular proliferation and hepatocarcinogenesis in mice.
Methods: Temporal hepatocyte-specific Myc disruption was achieved by use of the tamoxifen-inducible Cre-ERT2 recombinase system under control of the serum albumin promoter. Hepatocyte proliferation was assessed by administering peroxisome proliferator- activated receptor alpha (PPAR alpha) agonist Wy-14,643. A diethylnitrosamine-induced liver cancer model was used to evaluate the role of Myc in hepatocarcinogenesis.
Results: Tamoxifen administration induced recombination of Myc specifically in hepatocytes of Myc(fl/fl,ERT2)-Cre mice. When treated with a known hepatocellular proliferative stimulus Wy14,643, Myc(fl/fl,ERT2)-Cre mice showed a lower liver/body weight ratio and suppressed hepatocyte proliferation as compared to Myc(fl/fl) mice. Hepatic expression of cell cycle control genes, DNA repair genes, and Myc target gene miRNAs were upregulated in Wy-14,643-treated Myc(fl/fl) mouse livers, but not in Wy-14,643treated Myc(fl/fl,ERT2)-Cre livers. However, no differences were observed in the lipid-lowering effect of Wy-14,643 between Myc(fl/fl,ERT2)-Cre and Myc(fl/fl) mice, consistent with no differences in the expression of several PPAR alpha target genes involved in fatty acid beta-oxidation. Moreover, when subjected to the diethylnitrosamine liver cancer bioassay, Myc(fl/fl,ERT2)-Cre mice exhibited a markedly lower incidence of tumor formation compared with Mycfl/fl mice.
Conclusions: Myc plays an essential role in hepatocellular proliferation and liver tumorigenesis. Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver.
C1 [Qu, Aijuan; Jiang, Changtao; Cai, Yan; Kim, Jung-Hwan; Tanaka, Naoki; Shah, Yatrik M.; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Ward, Jerrold M.] Global VetPathol, Montgomery Village, MD 20886 USA.
[Shah, Yatrik M.] Univ Michigan, Sch Med, Div Gastroenterol, Dept Mol & Integrat Physiol & Internal Med, Ann Arbor, MI 48109 USA.
RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM gonzalef@mail.nih.gov
RI Cai, Yan/P-4383-2015
FU National Cancer Institute Intramural Research Program; National
Institutes of Health [CA148828]
FX This work was supported by the National Cancer Institute Intramural
Research Program, and National Institutes of Health Grant CA148828 (to
Y.M.S.).
NR 41
TC 14
Z9 14
U1 1
U2 13
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
EI 1600-0641
J9 J HEPATOL
JI J. Hepatol.
PD FEB
PY 2014
VL 60
IS 2
BP 331
EP 338
DI 10.1016/j.jhep.2013.09.024
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 291UJ
UT WOS:000329855600016
PM 24096051
ER
PT J
AU Marquardt, JU
Seo, D
Andersen, JB
Gillen, MC
Kim, MS
Conner, EA
Galle, PR
Factor, VM
Park, YN
Thorgeirsson, SS
AF Marquardt, Jens U.
Seo, Daekwan
Andersen, Jesper B.
Gillen, Matthew C.
Kim, Myoung Soo
Conner, Elizabeth A.
Galle, Peter R.
Factor, Valentina M.
Park, Young Nyun
Thorgeirsson, Snorri S.
TI Sequential transcriptome analysis of human liver cancer indicates late
stage acquisition of malignant traits
SO JOURNAL OF HEPATOLOGY
LA English
DT Article
DE Hepatocarcinogenesis; RNA sequencing; Molecular pathogenesis
ID HUMAN HEPATOCELLULAR-CARCINOMA; HIGH-THROUGHPUT; RNA-SEQ; C-MYC; GENES;
DIFFERENTIATION; GENOME; IDENTIFICATION; POLYMORPHISMS; ASSOCIATION
AB Background & Aims: Human hepatocarcinogenesis is as a multistep process starting from dysplastic lesions to early carcinomas (eHCC) that ultimately progress to HCC (pHCC). However, the sequential molecular alterations driving malignant transformation of the pre-neoplastic lesions are not clearly defined. This lack of information represents a major challenge in the clinical management of patients at risk.
Methods: We applied next-generation transcriptome sequencing to tumor-free surrounding liver (n = 7), low- (n = 4) and highgrade (n = 9) dysplastic lesions, eHCC (n = 5) and pHCC (n = 3) from 8 HCC patients with hepatitis B infection. Integrative analyses of genetic and transcriptomic changes were performed to characterize the genomic alterations during hepatocarcinogenesis.
Results: We report that changes in transcriptomes of early lesions including eHCC were modest and surprisingly homogenous. Extensive genetic alterations and subsequent activation of prognostic adverse signaling pathways occurred only late during hepatocarcinogenesis and were centered on TGFb, WNT, NOTCH, and EMT-related genes highlighting the molecular diversity of pHCC. We further identify IGFALS as a key genetic determinant preferentially down-regulated in pHCC.
Conclusions: Our results define new hallmarks in molecular stratification and therapy options for patients at risk for HCC, and merit larger prospective investigations to develop a modified clinical-decision making algorithm based on the individualized next-generation sequencing analyses. Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver.
C1 [Marquardt, Jens U.; Seo, Daekwan; Andersen, Jesper B.; Gillen, Matthew C.; Conner, Elizabeth A.; Factor, Valentina M.; Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Marquardt, Jens U.; Galle, Peter R.] Johannes Gutenberg Univ Mainz, Dept Med 1, Mainz, Germany.
[Park, Young Nyun] Yonsei Univ, Coll Med, Dept Pathol, Seoul, South Korea.
[Kim, Myoung Soo] Yonsei Univ, Coll Med, Dept Surg, Seoul, South Korea.
RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 4146, Bethesda, MD 20892 USA.
EM snorri_thorgeirsson@nih.gov
OI Andersen , Jesper B/0000-0003-1760-5244
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research; Korea Science and Engineering Foundation
(KOSEF); Korea government (MOST) [2011-0030707]; German Research
Foundation [MA 4443/2-1]
FX This work was supported by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research. This work was
partly supported by the Korea Science and Engineering Foundation (KOSEF)
grant funded by the Korea government (MOST) (2011-0030707) to Y.N.P.
J.U.M. is supported by a grant from the German Research Foundation (MA
4443/2-1).
NR 46
TC 16
Z9 17
U1 0
U2 17
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
EI 1600-0641
J9 J HEPATOL
JI J. Hepatol.
PD FEB
PY 2014
VL 60
IS 2
BP 346
EP 353
DI 10.1016/j.jhep.2013.10.014
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 291UJ
UT WOS:000329855600018
PM 24512821
ER
PT J
AU Aka, PV
Kuniholm, MH
Pfeiffer, RM
Wang, AS
Tang, W
Chen, S
Astemborski, J
Plankey, M
Villacres, MC
Peters, MG
Desai, S
Seaberg, EC
Edlin, BR
Strickler, HD
Thomas, DL
Prokunina-Olsson, L
Sharp, GB
O'Brien, TR
AF Aka, Peter V.
Kuniholm, Mark H.
Pfeiffer, Ruth M.
Wang, Alan S.
Tang, Wei
Chen, Sabrina
Astemborski, Jacquie
Plankey, Michael
Villacres, Maria C.
Peters, Marion G.
Desai, Seema
Seaberg, Eric C.
Edlin, Brian R.
Strickler, Howard D.
Thomas, David L.
Prokunina-Olsson, Ludmila
Sharp, Gerald B.
O'Brien, Thomas R.
TI Association of the IFNL4-Delta G Allele With Impaired Spontaneous
Clearance of Hepatitis C Virus
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE genetic; HCV; IFNL4; IL28B; viral clearance
ID MULTIETHNIC COHORT; GENETIC-VARIATION; IL28B
AB Interferon lambda 4 protein can be generated in IFNL4-Delta G carriers but not IFNL4-TT homozygotes. We studied 890 anti-hepatitis C virus (HCV)-positive participants in the Women's Interagency HIV Study. Among blacks (n = 555), HCV was more often cleared for those with genotype IFNL4-TT/TT (32.6%; odds ratio [OR], 3.59; P = 3.3 x 10(-5)) than IFNL4-TT/Delta G (11.3%; OR, 0.95; P = .86) or IFNL4-Delta G/Delta G (11.9%; referent). Pooling these data with published results in blacks (n = 1678), ORs were 3.84 (P = 8.6 x 10(-14)) for IFNL4-TT/TT and 1.44 (P = .03) IFNL4-TT/Delta G, and the area under the curve was 0.64 for IFNL4-Delta G genotype and 0.61 for rs12979860 (IL28B). IFNL4-Delta G is strongly associated with impaired spontaneous HCV clearance.
C1 [Aka, Peter V.; Wang, Alan S.; O'Brien, Thomas R.] NIH, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Pfeiffer, Ruth M.] NIH, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Tang, Wei; Prokunina-Olsson, Ludmila] NIH, Lab Translat Genom, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Sharp, Gerald B.] NIAID, Epidemiol Branch, Div Aids, NIH, Bethesda, MD 20892 USA.
[Kuniholm, Mark H.; Strickler, Howard D.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
[Chen, Sabrina] Informat Management Serv Inc, Calverton, MD USA.
[Astemborski, Jacquie; Seaberg, Eric C.; Thomas, David L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Plankey, Michael] Georgetown Univ, Med Ctr, Div Infect Dis, Washington, DC 20007 USA.
[Villacres, Maria C.] Univ So Calif, Dept Pediat, Los Angeles, CA 90089 USA.
[Peters, Marion G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Desai, Seema] Rush Univ, Med Ctr, Dept Immunol & Microbiol, Chicago, IL 60612 USA.
[Edlin, Brian R.] Natl Dev & Res Inst, Inst Infect Dis Res, New York, NY USA.
RP O'Brien, TR (reprint author), NIH, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,6E108,MSC 9767, Bethesda, MD 20892 USA.
EM obrient@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health
(National Cancer Institute, Division of Cancer Epidemiology and
Genetics); National Institute of Allergy and Infectious Diseases
[U01-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993,
UO1-AI-42590]; Eunice Kennedy Shriver National Institute of Child Health
and Human Development [UO1-HD-32632]; National Cancer Institute;
National Institute on Drug Abuse; National Institute on Deafness and
Other Communication Disorders; National Center for Research Resources
(UCSF-CTSI frant) [UL1 RR024131]; National Institutes of Drug Abuse
[DA033541, DA12568, DA04334]; National Institutes of Health
[R01-DA09532, R01-DA12109, R01-DA13245, R01-DA16159]; National Cancer
Institute [N02-CP-91027, N01-CO-12400]; Substance Abuse and Mental
Health Services Administration [H79-TI12103]; [R01013324]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health (National Cancer Institute, Division of
Cancer Epidemiology and Genetics). Data in this manuscript were
collected by the Women's Interagency HIV Study (WIHS) Collaborative
Study Group with centers (principal investigators) located at: New York
City/Bronx Consortium (Kathryn Anastos); Brooklyn, NY (Howard Minkoff);
Washington DC Metropolitan Consortium (Mary Young); The Connie Wofsy
Study Consortium of Northern California (Ruth Greenblatt); Los Angeles
County/Southern California Consortium (Alexandra Levine); Chicago
Consortium (Mardge Cohen); and Data Analysis Center (Stephen Gange). The
WIHS is funded by the National Institute of Allergy and Infectious
Diseases (U01-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989,
UO1-AI-34993, and UO1-AI-42590) and by the Eunice Kennedy Shriver
National Institute of Child Health and Human Development (UO1-HD-32632).
The WIHS is co-funded by the National Cancer Institute, the National
Institute on Drug Abuse, and the National Institute on Deafness and
Other Communication Disorders. Funding is also provided by the National
Center for Research Resources (UCSF-CTSI frant UL1 RR024131). The ALIVE
cohort is funded by the National Institutes of Drug Abuse DA033541,
DA12568, and DA04334 and genetic testing in that cohort by R01013324.
The Urban Health Study was funded by National Institutes of Health
grants R01-DA09532, R01-DA12109, R01-DA13245 and R01-DA16159 (to B. R.
E.); National Cancer Institute contracts N02-CP-91027 and N01-CO-12400
(to B. R. E.); Substance Abuse and Mental Health Services Administration
grant H79-TI12103 (to B. R. E.)
NR 10
TC 43
Z9 44
U1 0
U2 9
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 FEB 1
PY 2014
VL 209
IS 3
BP 350
EP 354
DI 10.1093/infdis/jit433
PG 5
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 292SE
UT WOS:000329921700008
PM 23956438
ER
PT J
AU Wojcik, G
Latanich, R
Mosbruger, T
Astemborski, J
Kirk, GD
Mehta, SH
Goedert, JJ
Kim, AY
Seaberg, EC
Busch, M
Thomas, DL
Duggal, P
Thio, CL
AF Wojcik, Genevieve
Latanich, Rachel
Mosbruger, Tim
Astemborski, Jacquie
Kirk, Gregory D.
Mehta, Shruti H.
Goedert, James J.
Kim, Arthur Y.
Seaberg, Eric C.
Busch, Michael
Thomas, David L.
Duggal, Priya
Thio, Chloe L.
TI Variants in HAVCR1 Gene Region Contribute to Hepatitis C Persistence in
African Americans
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE human genetics; Tim 1; hepatitis C virus
ID GENOME-WIDE ASSOCIATION; SPONTANEOUS CLEARANCE; VIRUS-INFECTION;
IMPUTATION; GENOTYPES; OUTCOMES
AB To confirm previously identified polymorphisms in HAVCR1 that were associated with persistent hepatitis C virus (HCV) infection in individuals of African and of European descent, we studied 165 subjects of African descent and 635 subjects of European descent. Because the association was only confirmed in subjects of African descent (rs6880859; odds ratio, 2.42; P = .01), we then used 379 subjects of African descent (142 with spontaneous HCV clearance) to fine-map HAVCR1. rs111511318 was strongly associated with HCV persistence after adjusting for IL28B and HLA (adjusted P = 8.8 x 10(-4)), as was one 81-kb haplotype (adjusted P = .0006). The HAVCR1 genomic region is an independent genetic determinant of HCV persistence in individuals of African descent.
C1 [Wojcik, Genevieve; Kirk, Gregory D.; Mehta, Shruti H.; Seaberg, Eric C.; Thomas, David L.; Duggal, Priya] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
[Latanich, Rachel; Mosbruger, Tim; Astemborski, Jacquie; Kirk, Gregory D.; Thomas, David L.; Thio, Chloe L.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA.
[Goedert, James J.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Kim, Arthur Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Kim, Arthur Y.] Harvard Univ, Sch Med, Boston, MA USA.
[Busch, Michael] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Busch, Michael] Blood Syst Res Inst, Viral Reference Lab & Repository Core, San Francisco, CA USA.
RP Thio, CL (reprint author), Johns Hopkins Univ, Sch Med, 855 N Wolfe St, Baltimore, MD 21205 USA.
EM cthio@jhmi.edu
FU National Institutes of Health (NIH) [R01 DA013324, RO1-HL-076902,
DA04334, DA12568, UO1-AI-35004, UO1-AI-31834, UO1-AI-34994,
UO1-AI-34989, UO1-AI-34993, UO1-AI42590]; Eunice Kennedy Shriver
National Institute of Child Health and Human Development [UO1-HD-32632];
National Cancer Institute; National Institute on Drug Abuse; National
Institute on Deafness and Other Communication Disorders; National Center
for Research Resources (UCSF-CTSI) [UL1 RR024131]; Intramural Research
Program of the National Cancer Institute; NIH [U19-AI-066345,
R01-DA031056, R01-DA-033541]
FX This project was supported by the National Institutes of Health (NIH;
grant number R01 DA013324 to D. L. T.). REVELL is funded by the NIH
(grant number RO1-HL-076902). ALIVE is funded by the NIH (grant numbers
DA04334 to G. D. K., DA12568 to S. H. M.). The WIHS is funded by the NIH
(grant numbers UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989,
UO1-AI-34993, and UO1-AI42590) and by the Eunice Kennedy Shriver
National Institute of Child Health and Human Development (grant number
UO1-HD-32632). WIHS is cofunded by the National Cancer Institute, the
National Institute on Drug Abuse, the National Institute on Deafness and
Other Communication Disorders, and the National Center for Research
Resources (UCSF-CTSI grant number UL1 RR024131). MHCS II is supported in
part by the Intramural Research Program of the National Cancer
Institute. A. Y. K. is funded by the NIH (grant numbers U19-AI-066345,
R01-DA031056, and R01-DA-033541).
NR 14
TC 4
Z9 4
U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD FEB 1
PY 2014
VL 209
IS 3
BP 355
EP 359
DI 10.1093/infdis/jit444
PG 5
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 292SE
UT WOS:000329921700009
PM 23964107
ER
PT J
AU Prickett, TD
Zerlanko, B
Gartner, JJ
Parker, SCJ
Dutton-Regester, K
Lin, JC
Teer, JK
Wei, XM
Jiang, JJ
Chen, G
Davies, MA
Gershenwald, JE
Robinson, W
Robinson, S
Hayward, NK
Rosenberg, SA
Margulies, EH
Samuels, Y
AF Prickett, Todd D.
Zerlanko, Brad
Gartner, Jared J.
Parker, Stephen C. J.
Dutton-Regester, Ken
Lin, Jimmy C.
Teer, Jamie K.
Wei, Xiaomu
Jiang, Jiji
Chen, Guo
Davies, Michael A.
Gershenwald, Jeffrey E.
Robinson, William
Robinson, Steven
Hayward, Nicholas K.
Rosenberg, Steven A.
Margulies, Elliott H.
Samuels, Yardena
CA NISC Comparative Sequencing
TI Somatic Mutations in MAP3K5 Attenuate Its Proapoptotic Function in
Melanoma through Increased Binding to Thioredoxin
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Article
ID REGULATING KINASE 1; METASTATIC MELANOMA; CANCER STATISTICS; APOPTOSIS;
ACTIVATION; BRAF; REVEALS; ASK1; INHIBITION; PATHWAY
AB Patients with advanced metastatic melanoma have poor prognosis and the genetics underlying its pathogenesis are poorly understood. High-throughput sequencing has allowed comprehensive discovery of somatic mutations in cancer samples. Here, on analysis of our whole-genome and whole-exome sequencing data of 29 melanoma samples, we identified several genes that harbor recurrent nonsynonymous mutations. These included MAP3K5 (mitogen-activated protein kinase kinase kinase-5), which in a prevalence screen of 288 melanomas was found to harbor a R256C substitution in 5 cases. All MAP3K5-mutated samples were wild type for BRAF, suggesting a mutual exclusivity for these mutations. Functional analysis of the MAP3K5 R256C mutation revealed attenuation of MKK4 (mitogen-activated protein kinase kinase 4) activation through increased binding of the inhibitory protein thioredoxin (TXN/TRX-1/Trx), resulting in increased proliferation and anchorage-independent growth of melanoma cells. This mutation represents a potential target for the design of new therapies to treat melanoma.
C1 [Prickett, Todd D.; Zerlanko, Brad; Gartner, Jared J.; Parker, Stephen C. J.; Wei, Xiaomu; Jiang, Jiji; Samuels, Yardena] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
[Dutton-Regester, Ken; Hayward, Nicholas K.] QIMR Berghofer Med Res Inst, Oncogen Lab, Brisbane, Qld, Australia.
[Lin, Jimmy C.] Washington Univ, Sch Med, Dept Pathol & Immunol, Div Lab & Genom Med, St Louis, MO USA.
[Teer, Jamie K.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
[NISC Comparative Sequencing] NHGRI, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA.
[Chen, Guo; Davies, Michael A.] Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Houston, TX 77030 USA.
[Chen, Guo; Davies, Michael A.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA.
[Gershenwald, Jeffrey E.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA.
[Gershenwald, Jeffrey E.] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA.
[Robinson, William; Robinson, Steven] Univ Colorado, Sch Med, Div Med Oncol, Aurora, CO USA.
[Robinson, Steven] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
[Margulies, Elliott H.] NHGRI, Genome Informat Sect, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
RP Samuels, Y (reprint author), Weizmann Inst Sci, Dept Mol Cell Biol, Wolfson Bldg,Room 534,POB 26,234 Herzl St, IL-76100 Rehovot, Israel.
EM Yardena.samuels@weizmann.ac.il
RI hayward, nicholas/C-1367-2015
OI hayward, nicholas/0000-0003-4760-1033
FU National Human Genome Research Institute; National Cancer Institute
[R21CA152432]; National Institutes of Health, USA; The University of
Texas MD Anderson Cancer Center Melanoma SPORE [P50 CA93459]; National
Health and Medical Research Council of Australia; National Cancer
Institute; Eli Lilly and Company; Israel Science Foundation [1604/13,
877/13]; Peter and Patricia Gruber Awards; ERC [StG-335377]
FX We thank Dr U Rudloff for acquiring tumor specimens, Drs Chris Schmidt
and Peter Parsons for establishment of the majority of melanoma cell
lines, and Drs V. Maduro, H. Abaan, and P. Cruz for generating the
sequence data analyzed here. We thank Dr V.G. Prieto for pathologic
review of the biospecimens from the Melanoma Informatics, Tissue
Resource, and Pathology Core (MelCore) at M.D. Anderson. We thank Dr T.
Wolfsberg for bioinformatics help, and J. Fekecs and D. Leja for
graphical assistance. This work was supported by the Intramural Research
Programs of the National Human Genome Research Institute, the National
Cancer Institute (R21CA152432 to RK), National Institutes of Health,
USA, The University of Texas MD Anderson Cancer Center Melanoma SPORE
(P50 CA93459), the National Health and Medical Research Council of
Australia, and by a public/private partnership between the Intramural
Research Programs of the National Human Genome Research Institute, the
National Cancer Institute, and Eli Lilly and Company coordinated by the
Foundation for the National Institutes of Health. YS is supported by the
Israel Science Foundation grant numbers 1604/13 and 877/13, a research
grant from the Peter and Patricia Gruber Awards, and the ERC
(StG-335377).
NR 42
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U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
EI 1523-1747
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD FEB
PY 2014
VL 134
IS 2
BP 452
EP 460
DI 10.1038/jid.2013.365
PG 9
WC Dermatology
SC Dermatology
GA 292IS
UT WOS:000329896000024
PM 24008424
ER
PT J
AU Liang, XY
Pfeiffer, RM
Li, WQ
Brossard, M
Burke, LS
Wheeler, W
Calista, D
Fargnoli, MC
Ghiorzo, P
Peris, K
Bianchi-Scarra, G
Chaudru, V
Zelenika, D
Maederl, D
Burdette, L
Yeager, M
Chanock, S
Landi, MT
Demenais, F
Tucker, MA
Goldstein, AM
Yang, XHR
AF Liang, Xueying
Pfeiffer, Ruth M.
Li, Wen-Qing
Brossard, Myriam
Burke, Laura S.
Wheeler, William
Calista, Donato
Fargnoli, Maria Concetta
Ghiorzo, Paola
Peris, Ketty
Bianchi-Scarra, Giovanna
Chaudru, Valerie
Zelenika, Diana
Maederl, Dennis
Burdette, Laurie
Yeager, Meredith
Chanock, Stephen
Landi, Maria Teresa
Demenais, Florence
Tucker, Margaret A.
Goldstein, Alisa M.
Yang, Xiaohong R.
TI Association of Genetic Variants in CDK6 and XRCC1 with the Risk of
Dysplastic Nevi in Melanoma-Prone Families
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Article
ID DNA-REPAIR; MEDITERRANEAN POPULATION; CUTANEOUS MELANOMA; CDKN2A
MUTATIONS; POLYMORPHISMS; MC1R; CANCER; PENETRANCE; ASIP
AB Dysplastic nevi (DN) is a strong risk factor for cutaneous malignant melanoma (CMM), and it frequently occurs in melanoma-prone families. To identify genetic variants for DN, we genotyped 677 tagSNPs in 38 melanoma candidate genes that are involved in pigmentation, DNA repair, cell cycle control, and melanocyte proliferation pathways in a total of 504 individuals (310 with DN, 194 without DN) from 53 melanoma-prone families (23 CDKN2A mutation positive and 30 negative). Conditional logistic regression, conditioning on families, was used to estimate the association between DN and each single-nucleotide polymorphism (SNP) separately, adjusted for age, sex, CMM, and CDKN2A status. P-values for SNPs in the same gene were combined to yield gene-specific P-values. Two genes, CDK6 (cyclin-dependent kinase 6) and XRCC1, were significantly associated with DN after Bonferroni correction for multiple testing (P=0.0001 and 0.00025, respectively), whereas neither gene was significantly associated with CMM. Associations for CDK6 SNPs were stronger in CDKN2A mutation-positive families (rs2079147, P-interaction = 0.0033), whereas XRCC1 SNPs had similar effects in mutation-positive and -negative families. The association for one of the associated SNPs in XRCC1 (rs25487) was replicated in two independent data sets (random-effect meta-analysis: P<0.0001). Our findings suggest that some genetic variants may contribute to DN risk independently of their association with CMM in melanoma-prone families.
C1 [Liang, Xueying; Pfeiffer, Ruth M.; Li, Wen-Qing; Burke, Laura S.; Maederl, Dennis; Burdette, Laurie; Yeager, Meredith; Chanock, Stephen; Landi, Maria Teresa; Tucker, Margaret A.; Goldstein, Alisa M.; Yang, Xiaohong R.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Liang, Xueying] US FDA, Off In Vitro Diagnost & Radiol Hlth, CDRH, Silver Spring, MD USA.
[Brossard, Myriam; Chaudru, Valerie; Demenais, Florence] INSERM, UMR 946, Genet Variat & Human Dis Unit, Paris, France.
[Brossard, Myriam; Chaudru, Valerie; Demenais, Florence] Univ Paris Diderot, Sorbonne Paris Cite, Inst Univ Hematol, Paris, France.
[Brossard, Myriam] Univ Paris Sud, F-94275 Le Kremlin Bicetre, France.
[Wheeler, William] Informat Management Serivces Inc, Rockville, MD USA.
[Calista, Donato] Osped Gen Provinciale M Bufalini, Dept Dermatol, Cesena, Italy.
[Fargnoli, Maria Concetta; Peris, Ketty] Univ Aquila, Dept Dermatol, I-67100 Laquila, Italy.
[Ghiorzo, Paola; Bianchi-Scarra, Giovanna] Univ Genoa, Dept Internal Med, I-16126 Genoa, Italy.
[Ghiorzo, Paola; Bianchi-Scarra, Giovanna] IRCCS AOU San Martino IST, Lab Genet Rare Hereditary Canc, Genoa, Italy.
[Chaudru, Valerie] Univ Evry Val dEssone, Evry, France.
[Zelenika, Diana] CEA, Inst Genom, Ctr Natl Genotypage, Evry, France.
RP Yang, XHR (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
EM Royang@mail.nih.gov
RI Demenais, Florence/G-3298-2013; Li, Wenqing/N-2293-2014; Tucker,
Margaret/B-4297-2015;
OI Demenais, Florence/0000-0001-8361-0936; Li, Wenqing/0000-0002-1283-4091;
Peris, Ketty/0000-0002-5237-0463; Fargnoli, Maria
Concetta/0000-0002-7249-2556
FU National Institutes of Health (NIH), National Cancer Institute (NCI);
Division of Cancer Epidemiology and Genetics (DCEG); Ligue Nationale
Contre le Cancer [PRE O5/FD, PRE 09/FD]; NIH, NCI, DCEG; NIH [CA
5558-01A2]
FX We are indebted to the participating families, whose generosity and
cooperation have made this study possible. We also acknowledge the
contributions to this work that were made by Virginia Pichler, Deborah
Zametkin, and Mary Fraser. This research was supported by the Intramural
Research Program of the National Institutes of Health (NIH), National
Cancer Institute (NCI), and Division of Cancer Epidemiology and Genetics
(DCEG). The French study was partly funded by Ligue Nationale Contre le
Cancer (PRE O5/FD and PRE 09/FD to FD and Doctoral fellowship to MB). We
thank the French NEVRISK study group that includes clinicians from
Hopital Saint-Louis, Fondation Rothschild, and Institut Gustave Roussy
for their contribution to patient recruitment and data collection. The
Italian studies were supported by the Intramural Research Program of
NIH, NCI, DCEG, and by R01 grant (CA 5558-01A2) from the NIH to MTL.
NR 25
TC 4
Z9 4
U1 1
U2 9
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
EI 1523-1747
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD FEB
PY 2014
VL 134
IS 2
BP 481
EP 487
DI 10.1038/jid.2013.316
PG 7
WC Dermatology
SC Dermatology
GA 292IS
UT WOS:000329896000027
PM 23892592
ER
PT J
AU Lindhurst, MJ
Wang, JA
Bloomhardt, HM
Witkowski, AM
Singh, LN
Bick, DP
Gambello, MJ
Powell, CM
Lee, CCR
Darling, TN
Biesecker, LG
AF Lindhurst, Marjorie J.
Wang, Ji-An
Bloomhardt, Hadley M.
Witkowski, Alison M.
Singh, Larry N.
Bick, David P.
Gambello, Michael J.
Powell, Cynthia M.
Lee, Chyi-Chia Richard
Darling, Thomas N.
Biesecker, Leslie G.
TI AKT1 Gene Mutation Levels Are Correlated with the Type of Dermatologic
Lesions in Patients with Proteus Syndrome
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Letter
ID EPIDERMAL NEVI; SKIN; CHALLENGES; MOSAICISM; DIAGNOSIS
C1 [Lindhurst, Marjorie J.; Bloomhardt, Hadley M.; Witkowski, Alison M.; Singh, Larry N.; Biesecker, Leslie G.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Wang, Ji-An; Darling, Thomas N.] Uniformed Serv Univ Hlth Sci, Dept Dermatol, Bethesda, MD 20814 USA.
[Bick, David P.] Med Coll Wisconsin, Dept Pediat & Obstet & Gynecol, Milwaukee, WI 53226 USA.
[Gambello, Michael J.] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA USA.
[Powell, Cynthia M.] Univ N Carolina, Dept Pediat & Genet, Chapel Hill, NC USA.
[Lee, Chyi-Chia Richard] NCI, NIH, Bethesda, MD 20892 USA.
RP Lindhurst, MJ (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA.
EM marjr@mail.nih.gov
RI Powell, Cynthia/L-5903-2015;
OI Darling, Thomas/0000-0002-5161-1974
FU Intramural NIH HHS [Z99 HG999999]
NR 14
TC 8
Z9 8
U1 1
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
EI 1523-1747
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD FEB
PY 2014
VL 134
IS 2
BP 543
EP 546
DI 10.1038/jid.2013.312
PG 4
WC Dermatology
SC Dermatology
GA 292IS
UT WOS:000329896000035
PM 23884311
ER
PT J
AU Turkbey, EB
Jain, A
Johnson, C
Redheuil, A
Arai, AE
Gomes, AS
Carr, J
Hundley, WG
Teixido-Tura, G
Eng, J
Lima, JAC
Bluemke, DA
AF Turkbey, Evrim B.
Jain, Aditya
Johnson, Craig
Redheuil, Alban
Arai, Andrew E.
Gomes, Antoinette S.
Carr, James
Hundley, W. Gregory
Teixido-Tura, Gisela
Eng, John
Lima, Joao A. C.
Bluemke, David A.
TI Determinants and Normal Values of Ascending Aortic Diameter by Age,
Gender, and Race/Ethnicity in the Multi-Ethnic Study of Atherosclerosis
(MESA)
SO JOURNAL OF MAGNETIC RESONANCE IMAGING
LA English
DT Article
DE thoracic aorta; MRI; normal value; cardiovascular risk factors
ID CARDIAC COMPUTED-TOMOGRAPHY; THORACIC AORTA; SURFACE-AREA; POPULATION;
ADULTS; MEDICINE; ANEURYSM; DISEASE; SIZE
AB PurposeTo determine the normal size and wall thickness of the ascending thoracic aorta (AA) and its relationship with cardiovascular risk factors in a large population-based study.
Materials and MethodsThe mean AA luminal diameter was measured in 3573 Multi-Ethnic Study of Atherosclerosis (MESA) participants (age: 45-84 years), using gradient echo phase contrast cine MRI. Multiple linear regression models were used to evaluate the associations between risk factors and AA diameter. The median and upper normal limit (95th percentile) was defined in a healthy subgroup as well as AA wall thickness.
ResultsThe upper limits of body surface area indexed AA luminal diameter for age categories of 45-54, 55-64, 65-74, and 75-84 years are 21, 22, 22, and 28 mm/m(2) in women and 20, 21, 22, 23 mm/m(2) in men, respectively. The mean AA wall thickness was 2.8 mm. Age, gender, and body surface area were major determinants of AA luminal diameter (approximate to+1 mm/10 years; approximate to+1.9 mm in men than women; approximate to+1 mm/ 0.23 m(2); P<0.001). The AA diameter in hypertensive subjects was +0.9 mm larger than in normotensives (P<0.001).
ConclusionAA diameter increases gradually with aging for both genders among all race/ethnicities. The normal value of AA diameter is provided. J. Magn. Reson. Imaging 2014;39:360-368. (c) 2013 Wiley Periodicals, Inc.
C1 [Turkbey, Evrim B.; Bluemke, David A.] NIH, Clin Ctr, Bethesda, MD 20892 USA.
[Jain, Aditya; Eng, John; Lima, Joao A. C.; Bluemke, David A.] Johns Hopkins Univ, Dept Radiol & Radiol Sci, Baltimore, MD USA.
[Johnson, Craig] Univ Washington, Sch Publ Hlth & Community Med, Dept Biostat, Seattle, WA 98195 USA.
[Redheuil, Alban] Univ Paris 05, HEGP Cardiovasc Imaging Dept, Paris, France.
[Redheuil, Alban] INSERM, U678, Paris, France.
[Arai, Andrew E.] NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA.
[Gomes, Antoinette S.] UCLA Sch Med, Dept Radiol, Los Angeles, CA USA.
[Carr, James] Northwestern Univ, Sch Med, Div Radiol, Chicago, IL USA.
[Hundley, W. Gregory] Wake Forest Univ Hlth Sci, Dept Internal Med Cardiol, Winston Salem, NC USA.
[Teixido-Tura, Gisela; Lima, Joao A. C.] Johns Hopkins Univ, Dept Med Cardiol, Baltimore, MD USA.
RP Bluemke, DA (reprint author), NIH, Clin Ctr, 9000 Rockville Pike,Bldg 10,Rm 1C355, Bethesda, MD 20892 USA.
EM bluemked@nih.gov
OI Teixido-Tura, Gisela/0000-0003-4714-2420; Bluemke,
David/0000-0002-8323-8086
FU National Heart, Lung, and Blood Institute; NIH [N01-HC-95159,
N01-HC-95169]
FX Contract grant sponsor: National Heart, Lung, and Blood Institute and
NIH intramural research program; Contract grand numbers: N01-HC-95159;
N01-HC-95169.
NR 23
TC 14
Z9 14
U1 1
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1053-1807
EI 1522-2586
J9 J MAGN RESON IMAGING
JI J. Magn. Reson. Imaging
PD FEB
PY 2014
VL 39
IS 2
BP 360
EP 368
DI 10.1002/jmri.24183
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 290KA
UT WOS:000329753400014
PM 23681649
ER
PT J
AU Peacock, ZS
Aghaloo, T
Bouloux, GF
Cillo, JE
Hale, RG
Le, AD
Lee, JS
Kademani, D
AF Peacock, Zachary S.
Aghaloo, Tara
Bouloux, Gary F.
Cillo, Joseph E., Jr.
Hale, Robert G.
Le, Anh D.
Lee, Janice S.
Kademani, Deepak
TI Proceedings From the 2013 American Association of Oral and Maxillofacial
Surgeons Research Summit
SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY
LA English
DT Article
ID BISPHOSPHONATE-RELATED OSTEONECROSIS; TRANSORAL ROBOTIC SURGERY;
ADVANCED OROPHARYNX CANCER; SQUAMOUS-CELL CARCINOMA; JAW-LIKE DISEASE;
RISK-FACTORS; MULTIPLE-MYELOMA; HUMAN-PAPILLOMAVIRUS;
SURGICAL-MANAGEMENT; PARATHYROID-HORMONE
AB The American Association of Oral and Maxillofacial Surgeons, the Oral and Maxillofacial Surgery Foundation, and the International Association of Oral and Maxillofacial Surgeons sponsored the fifth research summit, which convened on May 2 and 3 in Rosemont, Illinois. The Research Summits are convened biennially to facilitate the discussion and collaboration of oral and maxillofacial surgeons with clinical and basic science researchers in fields affecting the specialty. The goal is to advance the field of oral and maxillofacial surgery through exposure and education in topics that ultimately benefit the oral and maxillofacial surgical patient. This edition of the research summit included the topics of robotic surgery and antiresorptive-related osteonecrosis of the jaws (ARONJ). Most importantly, this research summit saw the development of research interest groups (RIGs) in the fields of anesthesia, maxillofacial oncology and reconstructive surgery, obstructive sleep apnea and orthognathic surgery, temporomandibular joint surgery, and trauma. These RIGs developed specific research goals with a plan to continue working on potential projects at the AAOMS Clinical Trials Course on May 7 to 9, 2013 at the University of Michigan in Ann Arbor. The summit program was developed by the AAOMS Committee on Research Planning and Technology Assessment. The charge of the committee is to encourage and promote research within the specialty and to encourage interdisciplinary collaboration. The research summit serves as a platform for oral and maxillofacial surgeons to lead the goal of advancement of research relevant to the specialty. This article provides an overview of the presentations that were made in the sessions on robotic surgery and ARONJ. The research summit keynote address and two additional presentations on patient registries are summarized and updates from the RIGs that were formed at the 2013 research summit are highlighted. (C) 2014 American Association of Oral and Maxillofacial Surgeons
C1 [Peacock, Zachary S.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA.
[Peacock, Zachary S.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA.
[Aghaloo, Tara] Univ Calif Los Angeles, Div Oral & Maxillofacial Surg, Los Angeles, CA USA.
[Bouloux, Gary F.] Emory Univ, Sch Med, Dept Surg, Div Oral & Maxillofacial Surg, Atlanta, GA 30322 USA.
[Cillo, Joseph E., Jr.] Allegheny Gen Hosp, Div Oral & Maxillofacial Surg, Pittsburgh, PA 15212 USA.
[Hale, Robert G.] US Army, Inst Surg Res, Ft Sam Houston, TX 78234 USA.
[Le, Anh D.] Univ Penn, Dept Oral & Maxillofacial Surg Pharmacol, Philadelphia, PA 19104 USA.
[Lee, Janice S.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA.
[Kademani, Deepak] Univ Minnesota, Div Oral & Maxillofacial Surg, Minneapolis, MN USA.
RP Peacock, ZS (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St,Warren 1201, Boston, MA 02114 USA.
EM zpeacock@partners.org
NR 95
TC 1
Z9 1
U1 0
U2 5
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0278-2391
EI 1531-5053
J9 J ORAL MAXIL SURG
JI J. Oral Maxillofac. Surg.
PD FEB
PY 2014
VL 72
IS 2
BP 241
EP 253
DI 10.1016/j.joms.2013.09.037
PG 13
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 290KV
UT WOS:000329756500005
PM 24438595
ER
PT J
AU Weisbrod, AB
Kitano, M
Thomas, F
Williams, D
Gulati, N
Gesuwan, K
Liu, YX
Venzon, D
Turkbey, I
Choyke, P
Yao, J
Libutti, SK
Nilubol, N
Linehan, WM
Kebebew, E
AF Weisbrod, Allison B.
Kitano, Mio
Thomas, Francine
Williams, David
Gulati, Neelam
Gesuwan, Krisana
Liu, Yixun
Venzon, David
Turkbey, Ismail
Choyke, Peter
Yao, Jack
Libutti, Steven K.
Nilubol, Naris
Linehan, William M.
Kebebew, Electron
TI Assessment of Tumor Growth in Pancreatic Neuroendocrine Tumors in von
Hippel Lindau Syndrome
SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
LA English
DT Article
ID ENETS CONSENSUS GUIDELINES; MERKEL CELL-CARCINOMA; PULMONARY NODULES;
SPONTANEOUS REGRESSION; ENDOCRINE TUMORS; CT; NEOPLASMS; MANAGEMENT;
DISEASE; CLASSIFICATION
AB BACKGROUND: The incidence of pancreatic neuroendocrine tumors (PNETs) is increasing, but only a subset of these heterogeneous tumors will progress to malignant disease, which is associated with a poor prognosis. Currently, there are limited data on the natural history of these tumors and it is difficult to determine which patients require surgical intervention because the risk of metastatic disease cannot be accurately determined.
STUDY DESIGN: We conducted a prospective study of 87 patients with von Hippel Lindau syndrome-associated solid pancreatic lesions to determine the natural history of these tumors with biochemical testing, follow-up anatomic and functional imaging, and advanced imaging analysis, with a median follow-up of 4 years.
RESULTS: Approximately 20% of consecutive tumor measurements during follow-up were decreased in size and 20% showed no change. This included 2 of 4 surgically proven malignant tumors, which had a net decrease in tumor size over time. Tumor volume, as derived from greatest diameter and volumetric measurements, showed good correlation to pathology tumor measurement of surgically resected tumors (Spearman rank correlation rho = 0.72, p = 0.0011, and rho = 0.83, p < 0.0001, respectively). Tumor density measurement had an inverse relationship with tumor size (Spearman rank correlation -0.22, p = 0.0047). A tumor density cutoff of 200 was 75% specific for malignant tumors.
CONCLUSIONS: Pancreatic neuroendocrine tumors demonstrate a nonlinear growth pattern, which includes periods of no growth and apparent decrease in size by imaging. These growth patterns are variable and are not associated with tumor grade and malignancy. Tumor density, as measured in this cohort, may offer a specific diagnostic tool for malignant disease. (J Am Coll Surg 2014; 218: 163-169. (C) 2014 by the American College of Surgeons)
C1 [Weisbrod, Allison B.; Kitano, Mio; Gulati, Neelam; Gesuwan, Krisana; Nilubol, Naris; Kebebew, Electron] Ctr Canc Res, Endocrine Oncol Branch, Bethesda, MD USA.
[Linehan, William M.] Ctr Canc Res, Urol Oncol Branch, Bethesda, MD USA.
[Thomas, Francine; Williams, David; Liu, Yixun; Turkbey, Ismail; Choyke, Peter; Yao, Jack] NCI, Dept Diagnost Radiol, Ctr Clin, NIH, Bethesda, MD 20892 USA.
[Venzon, David] NCI, Biostat & Data Management Sect, Off Clin Director, NIH, Bethesda, MD 20892 USA.
[Libutti, Steven K.] Montefiore Med Ctr, Dept Surg, Bronx, NY 10467 USA.
[Libutti, Steven K.] Albert Einstein Coll Med, Bronx, NY 10467 USA.
RP Kebebew, E (reprint author), NCI, Endocrine Oncol Branch, Bethesda, MD 20892 USA.
EM kebebewe@mail.nih.gov
FU intramural research program of the Center for Cancer Research, National
Cancer Institute, National Institutes of Health
FX This research was supported by the intramural research program of the
Center for Cancer Research, National Cancer Institute, National
Institutes of Health.
NR 37
TC 7
Z9 9
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1072-7515
EI 1879-1190
J9 J AM COLL SURGEONS
JI J. Am. Coll. Surg.
PD FEB
PY 2014
VL 218
IS 2
BP 163
EP 169
DI 10.1016/j.jamcollsurg.2013.10.025
PG 7
WC Surgery
SC Surgery
GA 290NB
UT WOS:000329763900005
PM 24440063
ER
PT J
AU Brownell, J
Bruckner, J
Wagoner, J
Thomas, E
Loo, YM
Gale, M
Liang, TJ
Polyak, SJ
AF Brownell, Jessica
Bruckner, Jacob
Wagoner, Jessica
Thomas, Emmanuel
Loo, Yueh-Ming
Gale, Michael, Jr.
Liang, T. Jake
Polyak, Stephen J.
TI Direct, Interferon-Independent Activation of the CXCL10 Promoter by
NF-kappa B and Interferon Regulatory Factor 3 during Hepatitis C Virus
Infection
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID TOLL-LIKE RECEPTOR-3; AIRWAY EPITHELIAL-CELLS; BINDING-PROTEIN-BETA;
GENE-EXPRESSION; TRANSCRIPTION FACTOR; SIGNALING PATHWAYS; IN-VITRO;
CYTOKINE EXPRESSION; INNATE IMMUNITY; HCV INFECTION
AB Hepatitis C virus (HCV) infection of hepatocytes leads to transcriptional induction of the chemokine CXCL10, which is considered an interferon (IFN)-stimulated gene. However, we have recently shown that IFNs are not required for CXCL10 induction in hepatocytes during acute HCV infection. Since the CXCL10 promoter contains binding sites for several proinflammatory transcription factors, we investigated the contribution of these factors to CXCL10 transcriptional induction during HCV infection in vitro. Wild-type and mutant CXCL10 promoter-luciferase reporter constructs were used to identify critical sites of transcriptional regulation. The proximal IFN-stimulated response element (ISRE) and NF-kappa B binding sites positively regulated CXCL10 transcription during HCV infection as well as following exposure to poly(I-C) (a Toll-like receptor 3 [TLR3] stimulus) and 5' poly(U) HCV RNA (a retinoic acid-inducible gene I [RIG-I] stimulus) from two viral genotypes. Conversely, binding sites for AP-1 and CCAAT/enhancer-binding protein (C/EBP-beta) negatively regulated CXCL10 induction in response to TLR3 and RIG-I stimuli, while only C/EBP-beta negatively regulated CXCL10 during HCV infection. We also demonstrated that interferonregulatory factor 3 (IRF3) is transiently recruited to the proximal ISRE during HCV infection and localizes to the nucleus in HCV-infected primary human hepatocytes. Furthermore, IRF3 activated the CXCL10 promoter independently of type I or type III IFN signaling. The data indicate that sensing of HCV infection by RIG-I and TLR3 leads to direct recruitment of NF-kappa B and IRF3 to the CXCL10 promoter. Our study expands upon current knowledge regarding the mechanisms of CXCL10 induction in hepatocytes and lays the foundation for additional mechanistic studies that further elucidate the combinatorial and synergistic aspects of immune signaling pathways.
C1 [Bruckner, Jacob; Wagoner, Jessica; Polyak, Stephen J.] Univ Washington, Harborview Med Ctr, Dept Lab Med, Seattle, WA 98104 USA.
[Thomas, Emmanuel] Univ Miami, Sylvester Canc Ctr, Viral Oncol Program, Miami, FL USA.
[Loo, Yueh-Ming; Gale, Michael, Jr.] Univ Washington, Dept Immunol, Seattle, WA 98195 USA.
[Liang, T. Jake] NIDDK, Bethesda, MD 20892 USA.
[Brownell, Jessica; Polyak, Stephen J.] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA.
RP Polyak, SJ (reprint author), Univ Washington, Harborview Med Ctr, Dept Lab Med, 325 9Th Ave, Seattle, WA 98104 USA.
EM polyak@uw.edu
FU National Institutes of Health (NIH) [U19AI066328, AI069285]; University
of Washington [NIH 2T32AI007509]
FX This work was supported by the National Institutes of Health (NIH
U19AI066328, AI069285) and a pathobiology predoctoral training grant
from the University of Washington (NIH 2T32AI007509).
NR 64
TC 27
Z9 27
U1 0
U2 9
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD FEB
PY 2014
VL 88
IS 3
BP 1582
EP 1590
DI 10.1128/JVI.02007-13
PG 9
WC Virology
SC Virology
GA 291UU
UT WOS:000329857000016
PM 24257594
ER
PT J
AU Dollery, SJ
Santiago-Crespo, RJ
Kardava, L
Moir, S
Berger, EA
AF Dollery, Stephen J.
Santiago-Crespo, Rey J.
Kardava, Lela
Moir, Susan
Berger, Edward A.
TI Efficient Infection of a Human B Cell Line with Cell-Free Kaposi's
Sarcoma-Associated Herpesvirus
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID EPSTEIN-BARR-VIRUS; PRIMARY EFFUSION LYMPHOMA; MULTICENTRIC CASTLEMAN
DISEASE; LYTIC GENE-EXPRESSION; LYMPHOPROLIFERATIVE DISORDERS; SURFACE
IMMUNOGLOBULIN; MONOCLONAL-ANTIBODIES; TRIGGERS REACTIVATION;
ENDOTHELIAL ORIGIN; PERIPHERAL-BLOOD
AB Kaposi's sarcoma-associated herpesvirus (KSHV) is causatively linked to two B cell lymphoproliferative disorders, multicentric Castleman's disease and primary effusion lymphoma. Latently infected B cells are a major KSHV reservoir, and virus activation from tonsillar B cells can result in salivary shedding and virus transmission. Paradoxically, human B cells (primary and continuous) are notoriously refractory to infection, thus posing a major obstacle to the study of KSHV in this cell type. By performing a strategic search of human B cell lymphoma lines, we found that MC116 cells were efficiently infected by cell-free KSHV. Upon exposure to recombinant KSHV. 219, enhanced green fluorescent protein reporter expression was detected in 17 to 20% of MC116 cells. Latent-phase transcription and protein synthesis were detected by reverse transcription-PCR and detection of latency- associated nuclear antigen expression, respectively, in cell lysates and individual cells. Selection based on the puromycin resistance gene in KSHV. 219 yielded cultures with all cells infected. After repeated passaging of the selected KSHV-infected cells without puromycin, latent KSHV was maintained in a small fraction of cells. Infected MC116 cells could be induced into lytic phase with histone deacetylase inhibitors, as is known for latently infected non-B cell lines, and also selectively by the B cell-specific pathway involving B cell receptor cross-linking. Lytic-phase transition was documented by red fluorescent protein reporter expression, late structural glycoprotein (K8.1A, gH) detection, and infectious KSHV production. MC116 cells were CD27(-)/CD10(+), characteristic of transitional B cells. These findings represent an important step in the establishment of an efficient continuous B cell line model to study the biologically relevant steps of KSHV infection.
C1 [Dollery, Stephen J.; Santiago-Crespo, Rey J.; Berger, Edward A.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
[Kardava, Lela; Moir, Susan] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
RP Berger, EA (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
EM edward_berger@nih.gov
FU Intramural Program of the NIH, NIAID
FX This research was funded in part by the Intramural Program of the NIH,
NIAID.
NR 69
TC 10
Z9 10
U1 0
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD FEB
PY 2014
VL 88
IS 3
BP 1748
EP 1757
DI 10.1128/JVI.03063-13
PG 10
WC Virology
SC Virology
GA 291UU
UT WOS:000329857000030
PM 24257608
ER
PT J
AU Teigler, JE
Phogat, S
Franchini, G
Hirsch, VM
Michael, NL
Barouch, DH
AF Teigler, Jeffrey E.
Phogat, Sanjay
Franchini, Genoveffa
Hirsch, Vanessa M.
Michael, Nelson L.
Barouch, Dan H.
TI The Canarypox Virus Vector ALVAC Induces Distinct Cytokine Responses
Compared to the Vaccinia Virus-Based Vectors MVA and NYVAC in Rhesus
Monkeys
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID SIMIAN IMMUNODEFICIENCY; INFECTIOUS-DISEASES; HELA-CELLS; VACCINATION;
CANDIDATES; SMALLPOX; STRAIN; PROTECTION; EFFICACY; TROPISM
AB Despite the growing use of poxvirus vectors as vaccine candidates for multiple pathogens and cancers, their innate stimulatory properties remain poorly characterized. Here we show that the canarypox virus-based vector ALVAC induced distinct systemic proinflammatory and antiviral cytokine and chemokine levels following the vaccination of rhesus monkeys compared to the vaccinia virus-based vectors MVA and NYVAC. These data suggest that there are substantial biological differences among leading poxvirus vaccine vectors that may influence resultant adaptive immune responses following vaccination.
C1 [Teigler, Jeffrey E.; Barouch, Dan H.] Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA.
[Teigler, Jeffrey E.; Barouch, Dan H.] MIT, Ragon Inst MGH, Boston, MA USA.
[Teigler, Jeffrey E.; Barouch, Dan H.] Harvard, Boston, MA USA.
[Phogat, Sanjay] Sanofi Pasteur Inc, Swiftwater, PA USA.
[Franchini, Genoveffa] NCI, Bethesda, MD 20892 USA.
[Hirsch, Vanessa M.] NIAID, Bethesda, MD 20892 USA.
[Michael, Nelson L.] Walter Reed Army Inst Res, US Mil HIV Res Program, Bethesda, MD USA.
RP Barouch, DH (reprint author), Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA.
EM dbarouch@bidmc.harvard.edu
FU National Institutes of Health [AI078526, AI096040, AI095985]; U.S.
Military HIV Research Program [W81XWH-07-2-0067]; Ragon Institute of
MGH, MIT, and Harvard; National Defense Science & Engineering Graduate
Fellowship; Herchel Smith Graduate Fellowship from Harvard University
FX We acknowledge support from the National Institutes of Health (AI078526,
AI096040, AI095985); the U.S. Military HIV Research Program
(W81XWH-07-2-0067); and the Ragon Institute of MGH, MIT, and Harvard
(D.H.B.); as well as a National Defense Science & Engineering Graduate
Fellowship and the Herchel Smith Graduate Fellowship from Harvard
University (J.E.T.).
NR 36
TC 21
Z9 21
U1 0
U2 10
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD FEB
PY 2014
VL 88
IS 3
BP 1809
EP 1814
DI 10.1128/JVI.02386-13
PG 6
WC Virology
SC Virology
GA 291UU
UT WOS:000329857000036
PM 24257612
ER
PT J
AU Wang, RX
Taubenberger, JK
AF Wang, Ruixue
Taubenberger, Jeffery K.
TI Characterization of the Noncoding Regions of the 1918 Influenza A H1N1
Virus
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID GENE; RNA; TRANSCRIPTION; PATHOGENESIS; EVOLUTION; SEGMENT; ORIGIN
AB The terminal noncoding region (NCR) sequences of the eight gene segments of the influenza A/Brevig Mission/1/1918 (H1N1) virus were determined by rapid amplification of cDNA ends (RACE). Chimeric viruses encoding the open reading frames of the 1918 virus but flanked by either the wild-type 1918 NCR sequences or the NCR sequences of two other H1N1 virus strains, A/WSN/1933 and A/New York/312/2001, were produced. No growth differences between the NCR variant 1918 influenza viruses were noted.
C1 [Wang, Ruixue; Taubenberger, Jeffery K.] NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Taubenberger, JK (reprint author), NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM taubenbergerj@niaid.nih.gov
FU Intramural Research Program of the NIH; NIAID
FX This work was supported by the Intramural Research Program of the NIH
and the NIAID.
NR 22
TC 2
Z9 2
U1 0
U2 6
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD FEB
PY 2014
VL 88
IS 3
BP 1815
EP 1818
DI 10.1128/JVI.03098-13
PG 4
WC Virology
SC Virology
GA 291UU
UT WOS:000329857000037
PM 24227852
ER
PT J
AU Riou, C
Burgers, WA
Mlisana, K
Koup, RA
Roederer, M
Karim, SSA
Williamson, C
Gray, CM
AF Riou, Catherine
Burgers, Wendy A.
Mlisana, Koleka
Koup, Richard A.
Roederer, Mario
Karim, Salim S. Abdool
Williamson, Carolyn
Gray, Clive M.
TI Differential Impact of Magnitude, Polyfunctional Capacity, and
Specificity of HIV-Specific CD8(+) T Cell Responses on HIV Set Point
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID VIRAL LOAD; ANTIVIRAL ACTIVITY; IMMUNE CONTROL; INFECTION; EPITOPE; GAG;
IMMUNODOMINANCE; PRESERVATION; REPLICATION; ASSOCIATION
AB Defining the characteristics of HIV-specific CD8(+) T cell responses that lead to viral control is crucial for vaccine development. We evaluated the differential impact of magnitude, polyfunctional capacity, and specificity of the CD8(+) response at approximately 6 months postinfection on the viral set point at 12 months in a cohort of HIV-infected individuals. High frequencies of Gag and Nef responses endowed with four functions were the best predictors of a low viral set point.
C1 [Riou, Catherine; Burgers, Wendy A.; Williamson, Carolyn] Univ Cape Town, Fac Hlth Sci, Inst Infect Dis & Mol Med, Div Med Virol, ZA-7925 Cape Town, South Africa.
[Gray, Clive M.] Univ Cape Town, Fac Hlth Sci, Inst Infect Dis & Mol Med, Div Immunol, ZA-7925 Cape Town, South Africa.
[Mlisana, Koleka; Karim, Salim S. Abdool] Univ KwaZulu Natal, Ctr AIDS Program Res South Africa CAPRISA, Durban, South Africa.
[Mlisana, Koleka] Univ KwaZulu Natal, Sch Lab Med & Med Sci, Dept Med Microbiol, Durban, South Africa.
[Koup, Richard A.] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Roederer, Mario] NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Burgers, WA (reprint author), Univ Cape Town, Fac Hlth Sci, Inst Infect Dis & Mol Med, Div Med Virol, ZA-7925 Cape Town, South Africa.
EM wendy.burgers@uct.ac.za
RI Abdool Karim, Salim Safurdeen/N-5947-2013;
OI Burgers, Wendy/0000-0003-3396-9398; Abdool Karim, Salim
Safurdeen/0000-0002-4986-2133; Mlisana, Koleka/0000-0002-8436-3268; ,
Carolyn/0000-0003-0125-1226
FU National Institute of Allergy and Infectious Diseases (NIAID), National
Institutes of Health (NIH) [AI51794, AI084387]; National Research
Foundation [67385]; LifeLab; biotechnology center of the South African
Government Department of Science and Technology; Columbia
University-Southern African Fogarty AIDS International Training and
Research Programme (AITRP); Fogarty International Center, NIH
[D43TW00231]; Wellcome Trust Intermediate Fellow in Public Health and
Tropical Medicine
FX This research has been supported by the National Institute of Allergy
and Infectious Diseases (NIAID), National Institutes of Health (NIH)
(grant no. AI51794 and AI084387), by the National Research Foundation
(grant no. 67385), and by a training grant from LifeLab, a biotechnology
center of the South African Government Department of Science and
Technology. W.A.B. was supported by a fellowship from the Columbia
University-Southern African Fogarty AIDS International Training and
Research Programme (AITRP) funded by the Fogarty International Center,
NIH (grant no. D43TW00231), and is a Wellcome Trust Intermediate Fellow
in Public Health and Tropical Medicine.
NR 31
TC 15
Z9 15
U1 0
U2 8
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD FEB
PY 2014
VL 88
IS 3
BP 1819
EP 1824
DI 10.1128/JVI.02968-13
PG 6
WC Virology
SC Virology
GA 291UU
UT WOS:000329857000038
PM 24227857
ER
PT J
AU Li, W
Avram, AV
Wu, B
Xiao, X
Liu, CL
AF Li, Wei
Avram, Alexandru V.
Wu, Bing
Xiao, Xue
Liu, Chunlei
TI Integrated Laplacian-based phase unwrapping and background phase removal
for quantitative susceptibility mapping
SO NMR IN BIOMEDICINE
LA English
DT Article
DE Laplacian; phase unwrapping; background phase removal; phase contrast;
quantitative susceptibility mapping
ID HIGH-FIELD MRI; HUMAN BRAIN; MAGNETIC-FIELD; IN-VIVO; ALGORITHM;
RECONSTRUCTION; ANISOTROPY; CONTRAST; DISEASE; COSMOS
AB Quantitative susceptibility mapping (QSM) is a recently developed MRI technique that provides a quantitative measure of tissue magnetic susceptibility. To compute tissue magnetic susceptibilities based on gradient echoes, QSM requires reliable unwrapping of the measured phase images and removal of contributions caused by background susceptibilities. Typically, the two steps are performed separately. Here, we present a method that simultaneously performs phase unwrapping and HARmonic (background) PhasE REmovaL using the LAplacian operator (HARPERELLA). Both numerical simulations and in vivo human brain images show that HARPERELLA effectively removes both phase wraps and background phase, whilst preserving all low spatial frequency components originating from brain tissues. When compared with other QSM phase preprocessing techniques, such as path-based phase unwrapping followed by background phase removal, HARPERELLA preserves the tissue phase signal in gray matter, white matter and cerebrospinal fluid with excellent robustness, providing a convenient and accurate solution for QSM. The proposed algorithm is provided, together with QSM and susceptibility tensor imaging (STI) tools, in a shared software package named STI Suite'. Copyright (c) 2013 John Wiley & Sons, Ltd.
C1 [Li, Wei; Avram, Alexandru V.; Wu, Bing; Xiao, Xue; Liu, Chunlei] Duke Univ, Sch Med, Brain Imaging & Anal Ctr, Durham, NC 27705 USA.
[Avram, Alexandru V.] Natl Inst Child Hlth & Human Dev NICHD, Sect Tissue Biophys & Biomimet, NIH, Bethesda, MD USA.
[Wu, Bing] GE Healthcare, Beijing, Peoples R China.
[Xiao, Xue] Tsinghua Univ, Sch Med, Dept Biomed Engn, Beijing 100084, Peoples R China.
[Liu, Chunlei] Duke Univ, Sch Med, Dept Radiol, Durham, NC 27705 USA.
RP Liu, CL (reprint author), Duke Univ, Sch Med, Brain Imaging & Anal Ctr, 2424 Erwin Rd,Suite 501,Campus Box 2737, Durham, NC 27705 USA.
EM chunlei.liu@duke.edu
OI Liu, Chunlei/0000-0001-8816-4832
FU National Institutes of Health (NIH) [R01 MH096979]; National Multiple
Sclerosis Society [RG4723]
FX The study was supported in part by the National Institutes of Health
(NIH) through grant R01 MH096979 and by the National Multiple Sclerosis
Society through grant RG4723 to C.L.
NR 39
TC 30
Z9 31
U1 2
U2 20
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0952-3480
EI 1099-1492
J9 NMR BIOMED
JI NMR Biomed.
PD FEB
PY 2014
VL 27
IS 2
BP 219
EP 227
DI 10.1002/nbm.3056
PG 9
WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
GA 293PY
UT WOS:000329986900012
PM 24357120
ER
PT J
AU Takebe, N
Nguyen, D
Yang, SX
AF Takebe, Naoko
Dat Nguyen
Yang, Sherry X.
TI Targeting Notch signaling pathway in cancer: Clinical development
advances and challenges
SO PHARMACOLOGY & THERAPEUTICS
LA English
DT Review
DE Clinical trials; Biomarkers; Diarrhea; Notch signaling; Monoclonal
antibodies (rnAbs); gamma-Secretase inhibitors
ID GAMMA-SECRETASE INHIBITOR; ADVANCED SOLID TUMORS; ACUTE
LYMPHOBLASTIC-LEUKEMIA; MAMMARY STEM-CELLS; EPITHELIAL-MESENCHYMAL
TRANSITION; HUMAN BREAST-CANCER; NF-KAPPA-B; PHASE-I; CHROMOSOMAL
TRANSLOCATIONS; FATE DETERMINATION
AB Notch signaling plays an important role in development and cell fate determination, and it is deregulated in human hematologic malignancies and solid tumors. This review includes a brief introduction of the relevant pathophysiology of Notch signaling pathway and primarily focuses on the clinical development of promising agents that either obstruct Notch receptor cleavages such as gamma-secretase inhibitors (GSIs) or interfere with the Notch ligand-receptor interaction by monoclonal antibodies (mAbs). Antitumor activity by GSIs and mAbs administered as single agent in early phases of clinical trials has been observed in advanced or metastatic thyroid cancer, non-small cell lung cancer, intracranial tumors, sarcoma or desmoid tumors, colorectal cancer with neuroendocrine features, melanoma and ovarian cancer. A number of mechanism-based adverse events particularly gastrointestinal toxicities emerged and mitigation strategies are developed after testing multiple GSIs and Notch targeting mAbs. We also discuss pharmacodynamic biomarkers in conjunction with methods of assessment of the molecular target inhibition validation. Biomarkers of efficacy or benefit may be of importance for a successful development of this class of drugs. Published by Elsevier Inc.
C1 [Takebe, Naoko] NCI, Div Canc Treatment & Diag, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA.
[Dat Nguyen; Yang, Sherry X.] NCI, Div Canc Treatment & Diag, Natl Clin Target Validat Lab, NIH, Bethesda, MD 20892 USA.
RP Takebe, N (reprint author), 9609 Med Ctr Dr Rm 5-W524,MSC9704, Rockville, MD 20850 USA.
EM takeben@mail.nih.gov; Sherry.Yang@nih.gov
FU Division of Cancer Treatment and Diagnosis, National Cancer Institute,
National Institutes of Health, Bethesda, Maryland, United States
FX We thank Dr. Richard Swerdlow (PSI International, Inc.) for his support
on the review article references. The Division of Cancer Treatment and
Diagnosis, National Cancer Institute, National Institutes of Health,
Bethesda, Maryland, United States in part supported this work.
NR 108
TC 99
Z9 109
U1 6
U2 70
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0163-7258
J9 PHARMACOL THERAPEUT
JI Pharmacol. Ther.
PD FEB
PY 2014
VL 141
IS 2
BP 140
EP 149
DI 10.1016/j.pharmthera.2013.09.005
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 293DF
UT WOS:000329950900003
PM 24076266
ER
PT J
AU Harouaka, R
Kang, ZG
Zheng, SY
Cao, L
AF Harouaka, Ramdane
Kang, Zhigang
Zheng, Si-Yang
Cao, Liang
TI Circulating tumor cells: Advances in isolation and analysis, and
challenges for clinical applications
SO PHARMACOLOGY & THERAPEUTICS
LA English
DT Review
DE Circulating tumor cells CTC; Cancer biomarker; Prognostic biomarker;
Predictive biomarker
ID METASTATIC BREAST-CANCER; RESISTANT PROSTATE-CANCER; MESENCHYMAL
TRANSITION MARKERS; IN-SITU HYBRIDIZATION; PERIPHERAL-BLOOD;
COLORECTAL-CANCER; LUNG-CANCER; PROGNOSTIC-SIGNIFICANCE; ABIRATERONE
ACETATE; ACQUIRED-RESISTANCE
AB Circulating tumor cells (CTCs) are rare cancer cells released from tumors into the bloodstream that are thought to have a key role in cancer metastasis. The presence of CTCs has been associated with worse prognosis in several major cancer types, including breast, prostate and colorectal cancer. There is considerable interest in CTC research and technologies for their potential use as cancer biomarkers that may enhance cancer diagnosis and prognosis, facilitate drug development, and improve the treatment of cancer patients. This review provides an update on recent progress in CTC isolation and molecular characterization technologies. Furthermore, the review covers significant advances and limitations in the clinical applications of CTC-based assays for cancer prognosis, response to anti-cancer therapies, and exploratory studies in biomarkers predictive of sensitivity and resistance to cancer therapies. Published by Elsevier Inc.
C1 [Harouaka, Ramdane; Zheng, Si-Yang] Penn State Univ, Dept Bioengn, University Pk, PA 16802 USA.
[Kang, Zhigang; Cao, Liang] NCI, Ctr Canc Res, Genet Branch, Bethesda, MD 20892 USA.
RP Cao, L (reprint author), NCI, Ctr Canc Res, Genet Branch, 37 Convent Dr,MSC 4265, Bethesda, MD 20892 USA.
EM caoli@mail.nih.gov
OI Harouaka, Ramdane/0000-0002-1425-3960
FU Intramural Research Program of the US National Cancer Institute (NCI) of
the National Institutes of Health; NCI [R21CA161835, DP2CA174508]
FX We thank Jennifer Crawford for editing the manuscript. This work is
directly supported by the Intramural Research Program of the US National
Cancer Institute (NCI) of the National Institutes of Health (Z.K and
L.C.) and by the NCI (R21CA161835, DP2CA174508, R.H. and S.Z.) in
preparing the manuscript. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government.
NR 146
TC 44
Z9 48
U1 8
U2 125
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0163-7258
J9 PHARMACOL THERAPEUT
JI Pharmacol. Ther.
PD FEB
PY 2014
VL 141
IS 2
BP 209
EP 221
DI 10.1016/j.pharmthera.2013.10.004
PG 13
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 293DF
UT WOS:000329950900008
PM 24134902
ER
PT J
AU Schnermann, J
AF Schnermann, J.
TI The maturing relationship between tubules and glomeruli in diabetes
mellitus
SO ACTA PHYSIOLOGICA
LA English
DT Editorial Material
ID TUBULOGLOMERULAR FEEDBACK; HYPERFILTRATION; REABSORPTION; SALT
C1 NIDDK, NIH, Bethesda, MD 20892 USA.
RP Schnermann, J (reprint author), NIDDK, NIH, Bethesda, MD 20892 USA.
EM jurgens@intra.niddk.nih.gov
NR 15
TC 0
Z9 0
U1 0
U2 4
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 FEB
PY 2014
VL 210
IS 2
BP 233
EP 235
DI 10.1111/apha.12161
PG 3
WC Physiology
SC Physiology
GA 287DE
UT WOS:000329519500009
PM 23998920
ER
PT J
AU Zeng, W
Cote, J
Chen, X
Kim, YA
Wei, W
Suh, K
Wang, B
Shi, ZJ
AF Zeng, Wei
Cote, Jordan
Chen, Xian
Kim, Yoo-Ah
Wei, Wei
Suh, Kyoungwon
Wang, Bing
Shi, Zhijie Jerry
TI Delay monitoring for wireless sensor networks: An architecture using air
sniffers
SO AD HOC NETWORKS
LA English
DT Article
DE Delay monitoring; Abnormal delay detection; Wireless sensor networks;
Sensor network management
AB Wireless sensor networks have been used for many delay-sensitive and safety-critical applications, e.g., emergency response and plant automation. For such applications, delay measurement inside the sensor networks is important for real-time monitoring and control of the networked system, and abnormal delay detection. In this paper, we propose a measurement architecture using distributed air sniffers. This approach provides convenient delay measurement, and requires no clock synchronization or instrumentation at the sensor nodes. Since using sniffers incurs additional deployment cost, we investigate two aspects to reduce deployment cost: (1) using inexpensive mote-class sniffers and (2) carefully placing the sniffers to minimize the number of sniffers that are needed. Specifically, we experimentally quantify the capability and fidelity of mote-class sniffers for delay measurement, and show that they provide satisfactory monitoring performance. We further formulate and solve a sniffer placement problem that minimizes the number of sniffers while taking account of the workload constraints of the sniffers, and show that the number of sniffers under our sniffer placement algorithms is only a small fraction of the number of sensor nodes in the network. Last, we demonstrate the effectiveness of our architecture for abnormal delay detection using experiments in a testbed. (C) 2013 Elsevier B.V. All rights reserved.
C1 [Zeng, Wei; Cote, Jordan; Chen, Xian; Wei, Wei; Wang, Bing; Shi, Zhijie Jerry] Univ Connecticut, Dept Comp Sci & Engn, Storrs, CT 06269 USA.
[Kim, Yoo-Ah] NIH, Natl Biotechnol Ctr, Bethesda, MD 20892 USA.
[Suh, Kyoungwon] Illinois State Univ, Sch Informat Technol, Normal, IL USA.
RP Zeng, W (reprint author), Univ Connecticut, Dept Comp Sci & Engn, Storrs, CT 06269 USA.
EM Wei.Zeng@engr.uconn.edu; jordocote@gmail.com; Xian.Chen@engr.uconn.edu;
Yoo-ah.Kim@nih.hhs.gov; weiwei@engr.uconn.edu; kwsuh@ilstu.edu;
bing@engr.uconn.edu; zshi@engr.uconn.edu
FU NSF CAREER [0746841, 0644188]; DOE GAANN Program [P200A090340]
FX Preliminary results of this paper are presented in [30,8]. This work was
supported in part by NSF CAREER Awards 0746841 and 0644188. It was
additionally supported by DOE GAANN Program Award P200A090340. We would
like to thank M. Zink for helpful discussions.
NR 34
TC 3
Z9 3
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1570-8705
EI 1570-8713
J9 AD HOC NETW
JI Ad Hoc Netw.
PD FEB
PY 2014
VL 13
BP 549
EP 559
DI 10.1016/j.adhoc.2013.10.008
PN B
PG 11
WC Computer Science, Information Systems; Telecommunications
SC Computer Science; Telecommunications
GA 288EO
UT WOS:000329595000022
ER
PT J
AU ter Bogt, TFM
de Looze, M
Molcho, M
Godeau, E
Hublet, A
Kokkevi, A
Kuntsche, E
Gabhainn, SN
Franelic, IP
Simons-Morton, B
Sznitman, S
Vieno, A
Vollebergh, W
Pickett, W
AF ter Bogt, Tom F. M.
de Looze, Margreet
Molcho, Michal
Godeau, Emmanuelle
Hublet, Anne
Kokkevi, Anna
Kuntsche, Emmanuel
Gabhainn, Saoirse Nic
Franelic, Iva Pejnovic
Simons-Morton, Bruce
Sznitman, Sharon
Vieno, Alessio
Vollebergh, Wilma
Pickett, William
TI Do societal wealth, family affluence and gender account for trends in
adolescent cannabis use? A 30 country cross-national study
SO ADDICTION
LA English
DT Article
DE Adolescence; cannabis use; family affluence; gender; societal wealth
ID EUROPEAN COUNTRIES; DRUG-USE; SMOKING; ALCOHOL
AB AimsTo examine cross-national changes in frequent adolescent cannabis use (40+ times consumed over life-time at age 15) over time and relate these trends to societal wealth, family affluence and gender.
DesignData from three cycles (2002, 2006, 2010) of the Health Behaviour in School-aged Children (HBSC) Study were used for cross-sectional and trend analyses of adolescent cannabis use.
SettingRepresentative surveys in 30 European and North American countries.
ParticipantsA total of 160606 15-year-old students.
MeasurementsRespondents' life-time cannabis use, demographics, family affluence (FAS) and frequency of peer contacts were measured individually. Indicators of wealth (gross domestic product per capita, GDP) and perceived availability of cannabis were obtained from national public data bases.
FindingsThe frequency of life-time cannabis use decreased over time among adolescents in Europe and North America, particularly in western European countries and the United States (relative risk (RR)=0.86: confidence interval (CI) 0.79-0.93). This trend was not observed consistently in rapidly developing countries in eastern, central and southern Europe. Over time (2002-10), cannabis use became: (i) less characteristic of high GDP countries in contrast to lower GDP countries (RR=0.74: CI 0.57-0.95); (ii) less characteristic of youth from high FAS families in contrast to youth from low FAS families (RR=0.83: CI 0.72-0.96); and (iii) characterized by an increasing gender gap, i.e. consumption was higher among males (RR 1.26: CI 1.04-1.53). Perceived availability of cannabis and peer contacts remained strong predictors of frequent cannabis use.
ConclusionsAmong 30 European and North American countries, cannabis use appears to have trickled down' over time, with developing countries taking on the former (heavier) use pattern of richer countries, and less affluent youth taking on the former (heavier) use pattern of more affluent youth. Cannabis use continues to be more common among adolescent males than females.
C1 [ter Bogt, Tom F. M.; de Looze, Margreet; Vollebergh, Wilma] Univ Utrecht, Utrecht, Netherlands.
[Molcho, Michal; Gabhainn, Saoirse Nic] Natl Univ Ireland, Galway, Ireland.
[Godeau, Emmanuelle] Univ Toulouse, INSERM, UMR 1027, Toulouse, France.
[Godeau, Emmanuelle] Serv Med Rectorat Toulouse, Toulouse, France.
[Hublet, Anne] Univ Ghent, Dept Publ Hlth, B-9000 Ghent, Belgium.
[Kokkevi, Anna] Univ Mental Hlth Res Inst, Athens, Greece.
[Kuntsche, Emmanuel] Sucht Schweiz Res Inst, Lausanne, Switzerland.
[Kuntsche, Emmanuel] Radboud Univ Nijmegen, Inst Behav Sci, NL-6525 ED Nijmegen, Netherlands.
[Franelic, Iva Pejnovic] Croatian Natl Inst Publ Hlth, Zagreb, Croatia.
[Simons-Morton, Bruce] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA.
[Sznitman, Sharon] Univ Haifa, Sch Publ Hlth, IL-31999 Haifa, Israel.
[Vieno, Alessio] Univ Padua, Dipartimento Psicol Sviluppo & Socializzaz, Padua, Italy.
[Pickett, William] Queens Univ, Dept Publ Hlth Sci, Kingston, ON, Canada.
[Pickett, William] Queens Univ, Dept Emergency Med, Kingston, ON, Canada.
RP ter Bogt, TFM (reprint author), POB 80140, NL-3508 TC Utrecht, Netherlands.
EM t.f.m.terbogt@uu.nl
RI Vollebergh, Wilma/C-2323-2012;
OI VIENO, ALESSIO/0000-0003-4417-4822; Simons-Morton,
Bruce/0000-0003-1099-6617
FU Canadian Institutes of Health Research; Heart and Stroke Foundation of
Canada (Canada) [MOP 97962, PCR 101415]; Utrecht University, the
Netherlands; Intramural Research Program of the Eunice Kennedy Shriver
National Institute of Child Health and Human Development (United States)
FX This research was supported (in part) by grants from the Canadian
Institutes of Health Research and the Heart and Stroke Foundation of
Canada (MOP 97962; PCR 101415, Canada), Utrecht University, the
Netherlands, and the Intramural Research Program of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development (United
States).
NR 25
TC 12
Z9 12
U1 4
U2 17
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0965-2140
EI 1360-0443
J9 ADDICTION
JI Addiction
PD FEB
PY 2014
VL 109
IS 2
BP 273
EP 283
DI 10.1111/add.12373
PG 11
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA 287OE
UT WOS:000329551300023
PM 24261614
ER
PT J
AU Muller, BG
Futterer, JJ
Gupta, RT
Katz, A
Kirkham, A
Kurhanewicz, J
Moul, JW
Pinto, PA
Rastinehad, AR
Robertson, C
de la Rosette, J
Sanchez-Salas, R
Jones, JS
Ukimura, O
Verma, S
Wijkstra, H
Marberger, M
AF Muller, Berrend G.
Futterer, Jurgen J.
Gupta, Rajan T.
Katz, Aaron
Kirkham, Alexander
Kurhanewicz, John
Moul, Judd W.
Pinto, Peter A.
Rastinehad, Ardeshir R.
Robertson, Cary
de la Rosette, Jean
Sanchez-Salas, Rafael
Jones, J. Stephen
Ukimura, Osamu
Verma, Sadhna
Wijkstra, Hessel
Marberger, Michael
TI The role of magnetic resonance imaging (MRI) in focal therapy for
prostate cancer: recommendations from a consensus panel
SO BJU INTERNATIONAL
LA English
DT Article
DE prostate cancer; focal therapy; consensus; multiparametric magnetic
resonance imaging; prostate biopsies
ID CONTRAST-ENHANCED MRI; APPARENT DIFFUSION-COEFFICIENT; TRANSURETHRAL
ULTRASOUND THERAPY; INTENSITY FOCUSED ULTRASOUND; TRANSRECTAL HIFU
ABLATION; MULTI-PARAMETRIC MRI; PHASED-ARRAY COIL; ENDORECTAL MR; 3 T;
RADICAL PROSTATECTOMY
AB Objective
To establish a consensus on the utility of multiparametric magnetic resonance imaging (mpMRI) to identify patients for focal therapy.
Methods
Urological surgeons, radiologists, and basic researchers, from Europe and North America participated in a consensus meeting about the use of mpMRI in focal therapy of prostate cancer.
The consensus process was face-to-face and specific clinical issues were raised and discussed with agreement sought when possible. All participants are listed among the authors.
Topics specifically did not include staging of prostate cancer, but rather identifying the optimal requirements for performing MRI, and the current status of optimally performed mpMRI to (i) determine focality of prostate cancer (e.g. localising small target lesions of 0.5mL), (ii) to monitor and assess the outcome of focal ablation therapies, and (iii) to identify the diagnostic advantages of new MRI methods.
In addition, the need for transperineal template saturation biopsies in selecting patients for focal therapy was discussed, if a high quality mpMRI is available. In other words, can mpMRI replace the role of transperineal saturation biopsies in patient selection for focal therapy?
Results
Consensus was reached on most key aspects of the meeting; however, on definition of the optimal requirements for mpMRI, there was one dissenting voice.
mpMRI is the optimum approach to achieve the objectives needed for focal therapy, if made on a high quality machine (3T with/without endorectal coil or 1.5T with endorectal coil) and judged by an experienced radiologist.
Structured and standardised reporting of prostate MRI is paramount.
State of the art mpMRI is capable of localising small tumours for focal therapy.
State of the art mpMRI is the technique of choice for follow-up of focal ablation.
Conclusions
The present evidence for MRI in focal therapy is limited.
mpMRI is not accurate enough to consistently grade tumour aggressiveness.
Template-guided saturation biopsies are no longer necessary when a high quality state of the art mpMRI is available; however, suspicious lesions should always be confirmed by (targeted) biopsy.
C1 [Muller, Berrend G.; de la Rosette, Jean; Wijkstra, Hessel] AMC Univ Hosp, Dept Urol, Amsterdam, Netherlands.
[Futterer, Jurgen J.] Radboud Univ Nijmegen, Med Ctr, Dept Radiol, NL-6525 ED Nijmegen, Netherlands.
[Futterer, Jurgen J.] Univ Twente, MIRA Inst Biomed Technol & Tech Med, NL-7500 AE Enschede, Netherlands.
[Gupta, Rajan T.] Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA.
[Katz, Aaron] Winthrop Univ Hosp, Dept Urol, New York, NY USA.
[Kirkham, Alexander] Univ Coll London Hosp, Dept Radiol, London, England.
[Kurhanewicz, John] Univ Calif UCSF, Dept Radiol, San Francisco, CA USA.
[Moul, Judd W.] Duke Univ, Med Ctr, Div Urol, Durham, NC USA.
[Moul, Judd W.] Duke Univ, Med Ctr, Duke Canc Inst, Durham, NC USA.
[Pinto, Peter A.] NCI, Dept Urol, Bethesda, MD 20892 USA.
[Rastinehad, Ardeshir R.; Robertson, Cary] Smith Inst Urol, Dept Urol Radiol, New York, NY USA.
[Sanchez-Salas, Rafael] Inst Montsouris, Dept Urol, Paris, France.
[Jones, J. Stephen] Cleveland Clin Fdn, Dept Urol, Cleveland, OH 44195 USA.
[Ukimura, Osamu] Univ So Calif, Norris Canc Ctr, Dept Urol, Los Angeles, CA USA.
[Verma, Sadhna] Univ Cincinatti, Dept Radiol, Cincinnati, OH USA.
[Wijkstra, Hessel] Eindhoven Univ Technol, Dept Elect Engn, NL-5600 MB Eindhoven, Netherlands.
[Marberger, Michael] Med Univ Vienna, Dept Urol, Vienna, Austria.
RP Muller, BG (reprint author), Univ Amsterdam, Acad Med Ctr, Dept Urol, Room G4-236,Meibergdreef 9, NL-1105 AZ Amsterdam, Noord Holland, Netherlands.
EM berrend@gmail.com
RI futterer, jurgen/A-1455-2014; Gupta, Rajan/M-1571-2015
OI Gupta, Rajan/0000-0002-2984-5010
FU Health Tronics
FX Stephen Jones received an unrestricted research grant from Health
Tronics.
NR 74
TC 24
Z9 24
U1 0
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1464-4096
EI 1464-410X
J9 BJU INT
JI BJU Int.
PD FEB
PY 2014
VL 113
IS 2
BP 218
EP 227
DI 10.1111/bju.12243
PG 10
WC Urology & Nephrology
SC Urology & Nephrology
GA 287LV
UT WOS:000329544200025
PM 24215670
ER
PT J
AU Pinsky, PF
Parnes, HL
Andriole, G
AF Pinsky, Paul F.
Parnes, Howard L.
Andriole, Gerald
TI Mortality and complications after prostate biopsy in the Prostate, Lung,
Colorectal and Ovarian Cancer Screening (PLCO) trial
SO BJU INTERNATIONAL
LA English
DT Article
DE prostate biopsy; complications; mortality; prostate-specific antigen;
PSA
ID MEN
AB Objective
To examine mortality and morbidity after prostate biopsy in the intervention arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening (PLCO) trial.
Subjects and Methods
Abstractors from the PLCO trial recorded the types and dates of diagnostic follow-up procedures after positive screens and documented the types and dates of resultant complications. Cancers and deaths among the participants were tracked.
The mortality rate in the 120-day period after prostate biopsy was compared with a control rate of deaths in the 120-day period after a negative screen in men without biopsy.
Multivariate analysis was performed to control for potential confounders, including age, comorbidities and smoking.
Rates of any complication, infectious and non-infectious complications were computed among men with a negative biopsy. Multivariate analysis was used to examine the risk factors for complications.
Results
Of the 37345 men enrolled in the PLCO trial (intervention arm), 4861 had at least one biopsy after a positive screen and 28661 had a negative screen and no biopsy.
The 120-day mortality rate after biopsy was 0.95 (per 1000), compared with the control group rate of 1.8; the multivariate relative risk was 0.49 (95% CI: 0.2-1.1).
Among 3706 negative biopsies, the rates (per 1000) of any complication, infectious and non-infections complications were 20.2, 7.8 and 13.0, respectively.
A history of prostate enlargement or inflammation was significantly associated with higher rates of both infectious (odds ratio [OR] = 3.7) and non-infectious (OR = 2.2) complications. Black race was associated with a higher infectious complications rate (OR = 7.1) and repeat biopsy was associated with lower rates of non-infectious complications (OR = 0.3).
Conclusion
Mortality rates were not found to be higher after prostate biopsy in the PLCO trial and complications were relatively infrequent, with several risk factors identified.
C1 [Pinsky, Paul F.; Parnes, Howard L.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Andriole, Gerald] Washington Univ, Sch Med, St Louis, MO USA.
RP Pinsky, PF (reprint author), NCI, Canc Prevent Div, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
EM pp4f@nih.gov
FU National Cancer Institute
FX The PLCO trial was funded through contracts from the National Cancer
Institute.
NR 12
TC 13
Z9 13
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1464-4096
EI 1464-410X
J9 BJU INT
JI BJU Int.
PD FEB
PY 2014
VL 113
IS 2
BP 254
EP 259
DI 10.1111/bju.12368
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA 287LV
UT WOS:000329544200006
PM 24053621
ER
PT J
AU Travison, TG
Zhuang, WV
Lunetta, KL
Karasik, D
Bhasin, S
Kiel, DP
Coviello, AD
Murabito, JM
AF Travison, T. G.
Zhuang, W. V.
Lunetta, K. L.
Karasik, D.
Bhasin, S.
Kiel, D. P.
Coviello, A. D.
Murabito, J. M.
TI The heritability of circulating testosterone, oestradiol, oestrone and
sex hormone binding globulin concentrations in men: the Framingham Heart
Study
SO CLINICAL ENDOCRINOLOGY
LA English
DT Article
ID BONE-MINERAL DENSITY; ADULT MALE TWINS; MIDDLE-AGED MEN; OLDER MEN;
SERUM TESTOSTERONE; METABOLIC SYNDROME; INTERINDIVIDUAL VARIATION;
NONGENETIC FACTORS; HEALTHY-MEN; ELDERLY-MEN
AB ObjectiveCirculating testosterone, oestradiol and oestrone concentrations vary considerably between men. Although a substantial proportion of this variation may be attributed to morbidity and behavioural factors, these cannot account for its entirety, suggesting genetic inheritance as a potential additional determinant. The analysis described here was intended to estimate the heritability of male circulating total testosterone (TT), calculated free testosterone (cFT), oestrone (E1), oestradiol (E2) and sex hormone binding globulin (SHBG), along with the genetic correlation between these factors.
DesignCross-sectional, observational analysis of data from male members of the Offspring and Generation 3 cohorts of the Framingham Heart Study. Data were collected in the years 1998-2005.
ParticipantsA total of 3367 community-dwelling men contributed to the analysis, including 1066 father/son and 1284 brother pairs among other family relationships.
MeasurementsLevels of serum sex steroids (TT, E1 and E2) were measured by liquid chromatography-tandem mass spectrometry, SHBG by immunofluorometric assay and cFT by mass action equation. Heritability was obtained using variance components analysis with adjustment for covariates including age, diabetes mellitus, body mass index and smoking status.
ResultsAge-adjusted heritability estimates were 019, 040, 040, 030 and 041 for cFT, TT, E1, E2 and SHBG, respectively. Adjustment for covariates did not substantially attenuate these estimates; SHBG-adjusted TT results were similar to those obtained for cFT. Genetic correlation coefficients ((G)) indicated substantial genetic association between TT and cFT ((G)=068), between TT and SHBG (pG=087), between E1 and E2 ((G)=046) and between TT and E2 ((G)=048).
ConclusionCirculating testosterone, oestradiol and oestrone concentrations exhibit substantial heritability in adult men. Significant genetic association between testosterone and oestrogen levels suggests shared genetic pathways.
C1 [Travison, T. G.; Bhasin, S.; Coviello, A. D.] Brigham & Womens Hosp, Res Program Mens Hlth Aging & Metab, Boston, MA 02115 USA.
[Zhuang, W. V.; Lunetta, K. L.] Creighton Univ, Sch Med, Ctr Hlth Policy & Eth, Publ Hlth Program, Omaha, NE 68178 USA.
[Lunetta, K. L.; Murabito, J. M.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
[Kiel, D. P.] Harvard Univ, Sch Med, Inst Aging Res, Boston, MA USA.
[Coviello, A. D.] Boston Univ, Sch Med, Dept Med, Sect Prevent Med & Epidemiol, Boston, MA 02118 USA.
[Murabito, J. M.] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA.
RP Murabito, JM (reprint author), Natl Heart Lung & Blood Inst, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.
EM murabito@bu.edu
OI Kiel, Douglas/0000-0001-8474-0310; Karasik, David/0000-0002-8826-0530
FU NIH [1RO1AG31206, R21AG32598]; Pepper Older Americans Independence
Center [5P30AG031679]; National Institute on Aging [R01 AR/AG 41398];
CDC Foundation; Framingham Heart Study is funded by National Heart,
Blood, and Lung Institute [N01-HC-25195]; National Institute of
Arthritis, Musculoskeletal and Skin Diseases
FX This project was supported primarily by NIH grant 1RO1AG31206 and
R21AG32598. Additional support was provided by the Boston Claude D.
Pepper Older Americans Independence Center grant 5P30AG031679 from the
National Institute on Aging and by a grant from the CDC Foundation. The
Framingham Heart Study is funded by National Heart, Blood, and Lung
Institute (contract N01-HC-25195). DPK effort and some of the support
for sex steroid measures were funded by the National Institute of
Arthritis, Musculoskeletal and Skin Diseases and the National Institute
on Aging (R01 AR/AG 41398).
NR 42
TC 9
Z9 9
U1 1
U2 8
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 FEB
PY 2014
VL 80
IS 2
BP 277
EP 282
DI 10.1111/cen.12260
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 286HU
UT WOS:000329459200016
PM 23746309
ER
PT J
AU Sun, YN
Yolitz, J
Alberico, T
Sun, XP
Zou, SG
AF Sun, Yaning
Yolitz, Jason
Alberico, Thomas
Sun, Xiaoping
Zou, Sige
TI Lifespan extension by cranberry supplementation partially requires SOD2
and is life stage independent
SO EXPERIMENTAL GERONTOLOGY
LA English
DT Article
DE Aging; Dietary intervention; Nutraceutical; Botanical; Oxidative stress;
Life stage
ID DROSOPHILA-MELANOGASTER; SUPEROXIDE-DISMUTASE; IMPROVES HEALTH;
LONGEVITY; CURCUMIN; RESTRICTION; PHYTOCHEMICALS; EXPRESSION; GENES;
MICE
AB Many nutraceuticals and pharmaceuticals have been shown to promote healthspan and lifespan. However, the mechanisms underlying the beneficial effects of prolongevity interventions and the time points at which interventions should be implemented to achieve beneficial effects are not well characterized. We have previously shown that a cranberry-containing nutraceutical can promote lifespan in worms and flies and delay age-related functional decline of pancreatic cells in rats. Here we investigated the mechanism underlying lifespan extension induced by cranberry and the effects of short-term or life stage-specific interventions with cranberry on lifespan in Drosophila. We found that lifespan extension induced by cranberry was associated with reduced phosphorylation of ERK, a component of oxidative stress response MAPK signaling, and slightly increased phosphorylation of AKT, a component of insulin-like signaling. Lifespan extension was also associated with a reduced level of 4-hydroxynonenal protein adducts, a biomarker of lipid oxidation. Moreover, lifespan extension induced by cranberry was partially suppressed by knockdown of SOD2, a major mitochondrial superoxide scavenger. Furthermore, cranberry supplementation was administered in three life stages of adult flies, health span (3-30 days), transition span (31-60 days) and senescence span (61 days to the end when all flies died). Cranberry supplementation during any of these life stages extended the remaining lifespan relative to the non-supplemented and life stage-matched controls. These findings suggest that cranberry supplementation is sufficient to promote longevity when implemented during any life stage, likely through reducing oxidative damage. Published by Elsevier Inc.
C1 [Sun, Yaning; Yolitz, Jason; Alberico, Thomas; Sun, Xiaoping; Zou, Sige] NIA, Funct Genom Unit, Translat Gerontol Branch, Baltimore, MD 21224 USA.
RP Zou, SG (reprint author), NIA, Funct Genom Unit, Translat Gerontol Branch, Baltimore, MD 21224 USA.
EM zous@mail.nih.gov
FU National Institute on Aging, NIH [Z01-AG000366-06]
FX We thank Edward Spangler for critical reading of the manuscript, Decas
Botanical Inc. for providing cranberry extract and Drs. Yongqing Zhang
and Osorio Meirelles for help on statistical analyses. This work was
supported by the Intramural Research Program of the National Institute
on Aging, NIH to S. Z. (Grant number Z01-AG000366-06).
NR 38
TC 6
Z9 6
U1 1
U2 19
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0531-5565
EI 1873-6815
J9 EXP GERONTOL
JI Exp. Gerontol.
PD FEB
PY 2014
VL 50
BP 57
EP 63
DI 10.1016/j.exger.2013.11.020
PG 7
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 288JS
UT WOS:000329608500009
PM 24316039
ER
PT J
AU Camargo, MC
Kim, WH
Chiaravalli, AM
Kim, KM
Corvalan, AH
Matsuo, K
Yu, J
Sung, JJY
Herrera-Goepfert, R
Meneses-Gonzalez, F
Kijima, Y
Natsugoe, S
Liao, LM
Lissowska, J
Kim, S
Hu, N
Gonzalez, CA
Yatabe, Y
Koriyama, C
Hewitt, SM
Akiba, S
Gulley, ML
Taylor, PR
Rabkin, CS
AF Camargo, M. Constanza
Kim, Woo-Ho
Chiaravalli, Anna Maria
Kim, Kyoung-Mee
Corvalan, Alejandro H.
Matsuo, Keitaro
Yu, Jun
Sung, Joseph J. Y.
Herrera-Goepfert, Roberto
Meneses-Gonzalez, Fernando
Kijima, Yuko
Natsugoe, Shoji
Liao, Linda M.
Lissowska, Jolanta
Kim, Sung
Hu, Nan
Gonzalez, Carlos A.
Yatabe, Yashushi
Koriyama, Chihaya
Hewitt, Stephen M.
Akiba, Suminori
Gulley, Margaret L.
Taylor, Philip R.
Rabkin, Charles S.
TI Improved survival of gastric cancer with tumour Epstein-Barr virus
positivity: an international pooled analysis
SO GUT
LA English
DT Article
ID CLINICOPATHOLOGICAL FEATURES; PROGNOSTIC-SIGNIFICANCE; EXPRESSION
PROFILE; PROTEIN EXPRESSION; LYMPHOID STROMA; T-LYMPHOCYTES; CARCINOMA;
INFECTION; EBV; RISK
AB Background and objective About 9% of gastric carcinomas have Epstein-Barr virus (EBV) in the tumour cells, but it is unclear whether viral presence influences clinical progression. We therefore examined a large multicentre case series for the association of tumour EBV status with survival after gastric cancer diagnosis, accounting for surgical stage and other prognostic factors.
Methods We combined individual-level data on 4599 gastric cancer patients diagnosed between 1976 and 2010 from 13 studies in Asia (n=8), Europe (n=3), and Latin America (n=2). EBV positivity of tumours was assessed by in situ hybridisation. Mortality HRs for EBV positivity were estimated by Cox regression models stratified by study, adjusted for distributions of sex (71% male), age (mean 58years), stage (52% tumour-node-metastasis stages III or IV), tumour histology (49% poorly differentiated, 57% Lauren intestinal-type), anatomic subsite (70% non-cardia) and year of diagnosis. Variations by study and continent were assessed using study-specific HRs for EBV positivity.
Results During median 3.0years follow-up, 49% of patients died. Stage was strongly predictive of mortality, with unadjusted HRs (vs stage I) of 3.1 for stage II, 8.1 for stage III and 13.2 for stage IV. Tumour EBV positivity was 8.2% overall and inversely associated with stage (adjusted OR: 0.79 per unit change). Adjusted for stage and other confounders, EBV positivity was associated with lower mortality (HR, 0.72; 95% CI 0.61 to 0.86), with low heterogeneity among the study populations (p=0.2). The association did not significantly vary across patient or tumour characteristics. There was no significant variation among the three continent-specific HRs (p=0.4).
Conclusions Our findings suggest that tumour EBV positivity is an additional prognostic indicator in gastric cancer. Further studies are warranted to identify the mechanisms underlying this protective association.
C1 [Camargo, M. Constanza; Liao, Linda M.; Hu, Nan; Taylor, Philip R.; Rabkin, Charles S.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
[Kim, Woo-Ho] Seoul Natl Univ, Coll Med, Dept Pathol, Seoul 151, South Korea.
[Chiaravalli, Anna Maria] Osped Circolo Varese, Anat Pathol Unit, Varese, Italy.
[Chiaravalli, Anna Maria] Univ Insubria, Varese, Italy.
[Kim, Kyoung-Mee] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Pathol, Seoul, South Korea.
[Corvalan, Alejandro H.] Pontificia Univ Catolica Chile, Sch Med, Dept Hematol & Oncol, Santiago, Chile.
[Matsuo, Keitaro] Aichi Canc Ctr, Res Inst, Div Mol Epidemiol, Nagoya, Aichi 464, Japan.
[Yu, Jun; Sung, Joseph J. Y.] Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Inst Digest Dis, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China.
[Herrera-Goepfert, Roberto] Natl Canc Inst, Dept Pathol, Mexico City, DF, Mexico.
[Meneses-Gonzalez, Fernando] Secretaria Salud Mexico, Direcc Gen Adjunta Epidemiol, Programa Residencia Epidemiol, Mexico City, DF, Mexico.
[Kijima, Yuko; Natsugoe, Shoji; Koriyama, Chihaya; Akiba, Suminori] Kagoshima Univ, Grad Sch Med & Dent Sci, Kagoshima 890, Japan.
[Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr & Inst Oncol, Div Canc Epidemiol & Prevent, Warsaw, Poland.
[Kim, Sung] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Surg, Seoul, South Korea.
[Gonzalez, Carlos A.] Catalan Inst Oncol, Epidemiol Res Program, Unit Nutr Environm & Canc, Barcelona, Spain.
[Yatabe, Yashushi] Aichi Canc Ctr Hosp, Dept Pathol & Mol Diagnost, Nagoya, Aichi 464, Japan.
[Hewitt, Stephen M.] NCI, Tissue Array Res Program, Rockville, MD 20852 USA.
[Hewitt, Stephen M.] NCI, Appl Mol Pathol Lab, Pathol Lab, Rockville, MD 20852 USA.
[Gulley, Margaret L.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA.
RP Camargo, MC (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS 6116, Rockville, MD 20852 USA.
EM camargomc@mail.nih.gov
RI Camargo, M. Constanza/R-9891-2016; Kim, Sung/G-4114-2014; Gonzalez,
Carlos A/O-4651-2014; Yu, Jun /D-8569-2015
OI Hewitt, Stephen/0000-0001-8283-1788; Liao, Linda/0000-0002-1923-5294;
Matsuo, Keitaro/0000-0003-1761-6314; Gonzalez, Carlos
A/0000-0003-2822-9715;
FU USA National Institutes of Health, National Cancer Institute; Oak Ridge
Associated Universities' Research Associates/Specialists Program;
Japanese Ministry of Education, Culture, Sports, Science and Technology
[17015018, 221S0001]; JSPS A3 Foresight Program; Spanish Ministry of
Health [exp. PI070130, PI081420]; European Commission
[QLG1-CT-2001-01049]; Spanish Ministry of Health network RTICCC [ISCIII
RD06/0020/0091]; Chilean National Fund for Scientific and Technological
Development, Fondecyt [. 1111014]; Research Fund for the Control of
Infectious Diseases, RFCID, Hong Kong [11100022]
FX This work was supported in part by the Intramural Research Program of
the USA National Institutes of Health, National Cancer Institute, and
the Oak Ridge Associated Universities' Research Associates/Specialists
Program. The Hospital-based Epidemiologic Research Program at Aichi
Cancer Center II was supported by Grant-in-Aid for Scientific Research
on Priority Areas of Cancer (No. 17015018) and on Innovative Areas (No.
221S0001) from the Japanese Ministry of Education, Culture, Sports,
Science and Technology and JSPS A3 Foresight Program. The EPIC study was
supported by the Health Research Fund of the Spanish Ministry of Health
(exp. PI070130 and PI081420); European Commission FP5 (ref.
QLG1-CT-2001-01049); and Spanish Ministry of Health network RTICCC
(ISCIII RD06/0020/0091). The Chilean study was supported by the Chilean
National Fund for Scientific and Technological Development, Fondecyt
(No. 1111014). The Chinese study in Guangzhou was supported by the
Research Fund for the Control of Infectious Diseases, RFCID, Hong Kong
(No. 11100022).
NR 59
TC 57
Z9 60
U1 3
U2 22
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0017-5749
EI 1468-3288
J9 GUT
JI Gut
PD FEB
PY 2014
VL 63
IS 2
BP 236
EP 243
DI 10.1136/gutjnl-2013-304531
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 286SD
UT WOS:000329488100009
PM 23580779
ER
PT J
AU Dull, AB
George, AA
Goncharova, EI
Evans, JR
Wamiru, A
Cartner, LK
Hager, GL
McMahon, JB
AF Dull, Angie B.
George, Anuja A.
Goncharova, Ekaterina I.
Evans, Jason R.
Wamiru, Antony
Cartner, Laura K.
Hager, Gordon L.
McMahon, James B.
TI Identification of Compounds by High-Content Screening That Induce
Cytoplasmic to Nuclear Localization of a Fluorescent Estrogen Receptor
alpha Chimera and Exhibit Agonist or Antagonist Activity In Vitro
SO JOURNAL OF BIOMOLECULAR SCREENING
LA English
DT Article
DE estrogen receptor; high-content screening; cell-based assay; nuclear
translocation; cytotoxicity
ID HEALTHY POSTMENOPAUSAL WOMEN; BREAST-CANCER; NONALCOHOLIC
STEATOHEPATITIS; ADJUVANT TAMOXIFEN; PLUS PROGESTIN; TETROCARCIN-A;
ER-ALPHA; MECHANISMS; THERAPY; TRIAL
AB We have completed a robust high-content imaging screen for novel estrogen receptor (ER) agonists and antagonists by quantitation of cytoplasmic to nuclear translocation of an estrogen receptor chimera in 384-well plates. The screen was very robust, with Z values >0.7 and coefficients of variation (CV) <5%. The screen utilized a stably transfected green fluorescent protein-tagged glucocorticoid/estrogen receptor (GFP-GRER) chimera, which consisted of the N-terminus of the glucocorticoid receptor fused to the human ER ligand binding domain. The GFP-GRER exhibited cytoplasmic localization in the absence of ER ligands and translocated to the nucleus in response to stimulation with ER agonists and antagonists. The BD Pathway 435 imaging system was used for image acquisition, analysis of translocation dynamics, and cytotoxicity measurements. We screened 224,891 samples from our synthetic, pure natural product libraries, prefractionated natural product extracts library, and crude natural product extracts library, which produced a 0.003% hit rate. In addition to identifying several known ER ligands, five compounds were discovered that elicited significant activity in the screen. Transactivation potential studies demonstrated that two hit compounds behave as agonists, while three compounds elicited antagonist activity in MCF-7 cells.
C1 [Dull, Angie B.; Wamiru, Antony] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Frederick, MD USA.
[George, Anuja A.; Hager, Gordon L.] NCI, Bethesda, MD 20892 USA.
[Goncharova, Ekaterina I.; Evans, Jason R.] Data Management Serv Inc, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Cartner, Laura K.; McMahon, James B.] NCI, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA.
RP Dull, AB (reprint author), Otsuka Maryland Med Labs Inc, 9900 Med Ctr Dr, Rockville, MD 20850 USA.
EM dullab@gmail.com
RI George, Anuja/C-5963-2017
OI George, Anuja/0000-0003-2643-6307
FU National Cancer Institute, National Institutes of Health (NIH)
[HHSN26120080001E]; Intramural Research Program of the NIH, National
Cancer Institute, Center for Cancer Research
FX The authors disclosed receipt of the following financial support for the
research, authorship, and/or publication of this article: This project
has been funded in whole or in part with federal funds from the National
Cancer Institute, National Institutes of Health (NIH), under contract
HHSN26120080001E. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the U.S. government. This research
was supported in part by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research.
NR 27
TC 2
Z9 2
U1 2
U2 13
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1087-0571
EI 1552-454X
J9 J BIOMOL SCREEN
JI J. Biomol. Screen
PD FEB
PY 2014
VL 19
IS 2
BP 242
EP 252
DI 10.1177/1087057113504136
PG 11
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Chemistry, Analytical
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Chemistry
GA 290QP
UT WOS:000329773700006
PM 24051224
ER
PT J
AU Rabjohns, JLA
Park, YD
Dehdashti, J
Sun, W
Henderson, C
Zelazny, A
Metallo, SJ
Zheng, W
Williamson, PR
AF Rabjohns, Jennifer L. A.
Park, Yoon-Dong
Dehdashti, Jean
Sun, Wei
Henderson, Christina
Zelazny, Adrian
Metallo, Steven J.
Zheng, Wei
Williamson, Peter R.
TI A High-Throughput Screening Assay for Fungicidal Compounds against
Cryptococcus neoformans
SO JOURNAL OF BIOMOLECULAR SCREENING
LA English
DT Article
DE Cryptococcus neoformans; fungicidal screen; high-throughput screen;
alamarBlue assay
ID BROTH MICRODILUTION METHOD; AMPHOTERICIN-B; MENINGITIS; FLUCONAZOLE;
SUSCEPTIBILITY; VORICONAZOLE; INHIBITION; METABOLISM; INFECTION;
VIRULENCE
AB Cryptococcus neoformans is a pathogenic fungus that causes meningitis worldwide, particularly in human immunodeficiency virus (HIV)-infected individuals. Although amphotericin B is the gold standard treatment for cryptococcal meningitis, the toxicity and inconvenience of intravenous injection emphasize a need for development of new anticryptocccal drugs. Recent data from humans and animal studies suggested that a nutrient-deprived host environment may exist in cryptococcal meningitis. Thus, a screening assay for identifying fungicidal compounds under nutrient-deprived conditions may provide an alternative strategy to develop new anticryptococcal drugs for this disease. A high-throughput fungicidal assay was developed using a profluorescent dye, alamarBlue, to detect residual metabolic activity of C. neoformans under nutrient-limiting conditions. Screening the Library of Pharmacologically Active Compounds (LOPAC) with this assay identified a potential chemical scaffold, 10058-F4, that exhibited fungicidal activity in the low micromolar range. These results thus demonstrate the feasibility of this alamarBlue-based assay for high-throughput screening of fungicidal compounds under nutrient-limiting conditions for new anticryptococcal drug development.
C1 [Rabjohns, Jennifer L. A.; Park, Yoon-Dong; Williamson, Peter R.] NIH, Lab Clin Infect Dis, Bethesda, MD 20892 USA.
[Dehdashti, Jean; Sun, Wei; Zheng, Wei] NIH, Natl Ctr Advancing Translat Sci, Bethesda, MD 20892 USA.
[Henderson, Christina; Zelazny, Adrian] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
[Metallo, Steven J.] Georgetown Univ, Dept Chem, Washington, DC 20057 USA.
[Williamson, Peter R.] Univ Illinois, Dept Med, Infect Dis Sect, Chicago, IL 60680 USA.
RP Williamson, PR (reprint author), NIH, 9000 Rockville Pike,Bldg 10,Rm 11N222,MSC 1888, Bethesda, MD 20892 USA.
EM williamsonpr@mail.nih.gov
RI Zheng, Wei/J-8889-2014
OI Zheng, Wei/0000-0003-1034-0757
FU Intramural Research Program of the Therapeutics for Rare and Neglected
Diseases, National Center for Advancing Translational Sciences, National
Institutes of Health; National Institute of Allergy and Infectious
Diseases
FX The authors disclosed receipt of the following financial support for the
research, authorship, and/or publication of this article: This work was
supported by the Intramural Research Program of the Therapeutics for
Rare and Neglected Diseases, National Center for Advancing Translational
Sciences, National Institutes of Health and the intramural program of
the National Institute of Allergy and Infectious Diseases.
NR 30
TC 9
Z9 9
U1 1
U2 5
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1087-0571
EI 1552-454X
J9 J BIOMOL SCREEN
JI J. Biomol. Screen
PD FEB
PY 2014
VL 19
IS 2
BP 270
EP 277
DI 10.1177/1087057113496847
PG 8
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Chemistry, Analytical
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Chemistry
GA 290QP
UT WOS:000329773700009
PM 23896686
ER
PT J
AU Briggs-Gowan, MJ
Nichols, SR
Voss, J
Zobel, E
Carter, AS
McCarthy, KJ
Pine, DS
Blair, J
Wakschlag, LS
AF Briggs-Gowan, Margaret J.
Nichols, Sara R.
Voss, Joel
Zobel, Elvira
Carter, Alice S.
McCarthy, Kimberly J.
Pine, Daniel S.
Blair, James
Wakschlag, Lauren S.
TI Punishment insensitivity and impaired reinforcement learning in
preschoolers
SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY
LA English
DT Article
DE Psychopathic tendencies; reinforcement learning; punishment
insensitivity; low concern; early childhood; disruptive behavior;
development
ID CALLOUS-UNEMOTIONAL TRAITS; PSYCHOPATHIC TRAITS; CONDUCT PROBLEMS;
ANTISOCIAL-BEHAVIOR; DISRUPTIVE BEHAVIOR; COMMUNITY SAMPLE; CHILDHOOD;
DISORDERS; INDIVIDUALS; DYSFUNCTION
AB BackgroundYouth and adults with psychopathic traits display disrupted reinforcement learning. Advances in measurement now enable examination of this association in preschoolers. The current study examines relations between reinforcement learning in preschoolers and parent ratings of reduced responsiveness to socialization, conceptualized as a developmental vulnerability to psychopathic traits.
MethodsOne hundred and fifty-seven preschoolers (mean age 4.70.8years) participated in a substudy that was embedded within a larger project. Children completed the Stars-in-Jars' task, which involved learning to select rewarded jars and avoid punished jars. Maternal report of responsiveness to socialization was assessed with the Punishment Insensitivity and Low Concern for Others scales of the Multidimensional Assessment of Preschool Disruptive Behavior (MAP-DB).
ResultsPunishment Insensitivity, but not Low Concern for Others, was significantly associated with reinforcement learning in multivariate models that accounted for age and sex. Specifically, higher Punishment Insensitivity was associated with significantly lower overall performance and more errors on punished trials (passive avoidance').
ConclusionsImpairments in reinforcement learning manifest in preschoolers who are high in maternal ratings of Punishment Insensitivity. If replicated, these findings may help to pinpoint the neurodevelopmental antecedents of psychopathic tendencies and suggest novel intervention targets beginning in early childhood.
C1 [Briggs-Gowan, Margaret J.; McCarthy, Kimberly J.] Univ Connecticut, Ctr Hlth, Dept Psychiat, Farmington, CT 06032 USA.
[Nichols, Sara R.; Voss, Joel; Zobel, Elvira; Wakschlag, Lauren S.] Northwestern Univ, Dept Med Social Sci, Feinberg Sch Med, Chicago, IL 60611 USA.
[Carter, Alice S.] Univ Massachusetts, Dept Psychol, Boston, MA 02125 USA.
[Pine, Daniel S.; Blair, James] NIMH, Div Intramural Res Programs, Rockville, MD 20857 USA.
RP Briggs-Gowan, MJ (reprint author), Univ Connecticut, Ctr Hlth, Dept Psychiat, MC-1410,263 Farmington Ave, Farmington, CT 06032 USA.
EM mbriggsgowan@uchc.edu
FU NIMH [R01MH082830, U01MH090301]; Walden & Jean Young Shaw Foundation
FX This research was supported by grants from the NIMH (R01MH082830,
Wakschlag, PI; U01MH090301, Briggs-Gowan), as well as the Walden & Jean
Young Shaw Foundation. We gratefully acknowledge our collaborators Seung
Choi and David Henry for their contributions to modeling of the MAP-DB
and Seth Pollak for sharing his expertise in developmental modification
of tasks for young children. We thank Jackie Kestler for her superb
oversight of the MAPS study. We are also grateful to Ellen Kessel for
her important role in the development and piloting of the SIJ task with
preschoolers. The authors have declared that they have no competing or
potential conflicts of interest.
NR 36
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U1 9
U2 21
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0021-9630
EI 1469-7610
J9 J CHILD PSYCHOL PSYC
JI J. Child Psychol. Psychiatry
PD FEB
PY 2014
VL 55
IS 2
BP 154
EP 161
DI 10.1111/jcpp.12132
PG 8
WC Psychology, Developmental; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 289BW
UT WOS:000329657200008
PM 24033313
ER
PT J
AU Johnson, KC
Brennan, PA
Stowe, ZN
Leibenluft, E
Newport, DJ
AF Johnson, Katrina C.
Brennan, Patricia A.
Stowe, Zachary N.
Leibenluft, Ellen
Newport, D. Jeffrey
TI Physiological regulation in infants of women with a mood disorder:
examining associations with maternal symptoms and stress
SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY
LA English
DT Article
DE Bipolar; depression; RSA; heart rate; vagal; stress; infants; human
ID RESPIRATORY SINUS ARRHYTHMIA; HEART-RATE-VARIABILITY; AUTONOMIC
NERVOUS-SYSTEM; BIPOLAR DISORDER; DEPRESSED MOTHERS; SOCIAL-BEHAVIOR;
CHILDREN; REACTIVITY; EMOTION; PARENTS
AB BackgroundThe offspring of mothers with mood disorders may evidence increased behavioral problems as early as preschool; however, no study to date has examined psychophysiological characteristics during infancy, particularly among offspring of mothers diagnosed with bipolar disorder. Elucidating psychobiological mechanisms of risk early in development is critical to inform prevention and early intervention efforts.
MethodThis study compared physiological and behavioral responsivity in 6-month-old infants (N=329) of mothers with lifetime histories of bipolar disorder (BD, n=44), major depressive disorder (MDD, n=244), or no history of Axis I disorders (CTL, n=41). Infant respiratory sinus arrhythmia (RSA) was measured in a laboratory stressor paradigm. Measures of infant affect and behavior during mother-infant interaction, current maternal depressive symptoms, and exposure to stressful life events were examined with respect to diagnostic group and RSA.
ResultsGroups did not differ in baseline RSA or infant affect measures. However, during the stressor task, infants of mothers with BD evidenced increases in RSA, while infants of MDD and CTL mothers evidenced decreases in RSA. Though levels of postnatal stress and current levels of maternal depressive symptoms differed among groups, neither of these factors predicted infant psychophysiological responses.
ConclusionsAt 6months of age, infants of mothers with BD show differences in psychophysiological regulation. These differences cannot be accounted for by perinatal outcome, current maternal depressive symptoms, or exposure to stressful life events, and thus may reflect endophenotypic markers of psychopathological risk.
C1 [Johnson, Katrina C.] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA.
[Brennan, Patricia A.] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA.
[Stowe, Zachary N.] Univ Arkansas Med Sci, Inst Psychiat Res, Little Rock, AR 72205 USA.
[Leibenluft, Ellen] NIMH, Emot & Dev Branch, Bethesda, MD 20892 USA.
[Newport, D. Jeffrey] Ohio State Univ, Coll Med, Dept Psychiat, Columbus, OH 43210 USA.
[Newport, D. Jeffrey] Ohio State Univ, Coll Med, Dept Obstet & Gynecol, Columbus, OH 43210 USA.
RP Johnson, KC (reprint author), Emory Univ, Psychol & Interdisciplinary Sci Bldg,36 Eagle Row, Atlanta, GA 30322 USA.
EM kcederb@emory.edu
RI Newport, Donald/H-9846-2013;
OI Newport, D. Jeffrey/0000-0003-1695-9710
FU Brain and Behavior Research Foundation; Emory University Silvio O. Conte
Center for the Neurobiology of Mental Disease [MH58922]; Specialized
Center of Research (SCOR) on Sex and Gender Effects [MH68036]; National
Institute of Mental Health [MH71531, MH88609]; NARSAD; National
Institutes of Health (NIH); GlaxoSmithKline; Pfizer; Wyeth Corporations;
NIMH; Eli Lilly; GlaxoSmithKline (GSK); Janssen
FX This study was supported by Brain and Behavior Research Foundation
awards to Drs. Brennan and Johnson, the Emory University Silvio O. Conte
Center for the Neurobiology of Mental Disease (MH58922), the Specialized
Center of Research (SCOR) on Sex and Gender Effects (MH68036), and the
National Institute of Mental Health (MH71531, MH88609).; K.C.J. has
received research support from NARSAD. P.A.B. has received research
support from NARSAD and the National Institutes of Health (NIH). Z.N.S.
has received research support from, consulted to GlaxoSmithKline,
Pfizer, and Wyeth Corporations, and received speakers' honoraria from
the same companies plus from Eli Lilly and Forest Corporations. E. L.
receives research support from the NIMH intramural program. J.N. has
received research support from NARSAD and the National Institutes of
Health (NIH), as well as Eli Lilly, GlaxoSmithKline (GSK), Janssen, and
Wyeth Corporations, and speaker's honoraria from Astra-Zeneca
Pharmaceuticals (AZP), Eli Lilly, GSK, and Pfizer Corporations. No
coauthor or any family member holds equity positions in pharmaceutical
or biomedical corporations. The authors have declared that they have no
competing or potential conflicts of interest.
NR 40
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Z9 2
U1 6
U2 29
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0021-9630
EI 1469-7610
J9 J CHILD PSYCHOL PSYC
JI J. Child Psychol. Psychiatry
PD FEB
PY 2014
VL 55
IS 2
BP 191
EP 198
DI 10.1111/jcpp.12130
PG 8
WC Psychology, Developmental; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 289BW
UT WOS:000329657200012
PM 23981139
ER
PT J
AU Chaemsaithong, P
Chaiworapongsa, T
Romero, R
Korzeniewski, SJ
Stampalija, T
Than, NG
Dong, Z
Miranda, J
Yeo, L
Hassan, SS
AF Chaemsaithong, Piya
Chaiworapongsa, Tinnakorn
Romero, Roberto
Korzeniewski, Steven J.
Stampalija, Tamara
Than, Nandor Gabor
Dong, Zhong
Miranda, Jezid
Yeo, Lami
Hassan, Sonia S.
TI Maternal plasma soluble TRAIL is decreased in preeclampsia
SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
LA English
DT Article
DE Apoptosis; coronary artery disease; C-reactive protein; endothelial
cell; intravascular inflammation; neutrophil apoptosis
ID C-REACTIVE PROTEIN; APOPTOSIS-INDUCING LIGAND; FOR-GESTATIONAL-AGE;
INTRAUTERINE GROWTH RESTRICTION; CORONARY-HEART-DISEASE; SYSTEMIC
INFLAMMATORY RESPONSE; CIRCULATING ANGIOGENIC FACTORS; ENDOTHELIAL-CELL
DYSFUNCTION; LINKING PLACENTAL ISCHEMIA; PRETERM PREMATURE RUPTURE
AB Objective: Preeclampsia (PE) is characterized by systemic intravascular inflammation. Women who develop PE are at an increased risk for cardiovascular disease in later life. Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) has anti-atherosclerotic effects in endothelial cells and can mediate neutrophil apoptosis. Low soluble TRAIL (sTRAIL) and high C-reactive protein (CRP) concentrations are associated with an increased risk of future cardiovascular disease in non-pregnant individuals. The aim of this study was to determine whether maternal plasma concentrations of sTRAIL and CRP differ between women with PE and those with uncomplicated pregnancies.
Method: This cross-sectional study included women with an uncomplicated pregnancy (n=93) and those with PE (n=52). Maternal plasma concentrations of sTRAIL and CRP concentrations were determined by ELISA.
Results: 1) The median plasma sTRAIL concentration (pg/mL) was significantly lower and the median plasma CRP concentration was significantly higher in women with PE than in those with an uncomplicated pregnancy (25.55 versus 29.17; p=0.03 and 8.0 versus 4.1; p=0.001, respectively); 2) the median plasma concentration sTRAIL/CRP ratio was two-fold lower in women with PE than in those with an uncomplicated pregnancy (p<0.001); and 3) women with plasma sTRAIL and CRP ratio in the lowest quartile were 8 times more likely to have PE than women with concentrations in the upper three quartiles (OR 8.9; 95% CI: 2.8-27.8).
Conclusion: Maternal plasma sTRAIL concentrations are lower (while those of CRP are higher) in women with PE than in those with uncomplicated pregnancies. These findings are consistent with the evidence of intravascular inflammation in this disorder.
C1 [Chaemsaithong, Piya; Chaiworapongsa, Tinnakorn; Romero, Roberto; Korzeniewski, Steven J.; Stampalija, Tamara; Than, Nandor Gabor; Dong, Zhong; Miranda, Jezid; Yeo, Lami; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA.
[Chaemsaithong, Piya; Chaiworapongsa, Tinnakorn; Romero, Roberto; Korzeniewski, Steven J.; Stampalija, Tamara; Than, Nandor Gabor; Dong, Zhong; Miranda, Jezid; Yeo, Lami; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.
[Chaemsaithong, Piya; Chaiworapongsa, Tinnakorn; Korzeniewski, Steven J.; Stampalija, Tamara; Than, Nandor Gabor; Yeo, Lami; Hassan, Sonia S.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Stampalija, Tamara] IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy.
RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA.
EM romeror@mail.nih.gov
RI Stampalija, Tamara/K-4900-2014
FU Perinatology Research Branch, Division of Intramural Research, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, Department of Health and
Human Services (NICHD/NIH); NICHD, NIH [HHSN275201300006C]
FX This research was supported, in part, by the Perinatology Research
Branch, Division of Intramural Research, Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health, Department of Health and Human Services (NICHD/NIH); and, in
part, with Federal funds from NICHD, NIH under Contract No.
HHSN275201300006C.
NR 201
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U1 0
U2 1
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1476-7058
EI 1476-4954
J9 J MATERN-FETAL NEO M
JI J. Matern.-Fetal Neonatal Med.
PD FEB
PY 2014
VL 27
IS 3
BP 217
EP 227
DI 10.3109/14767058.2013.806906
PG 11
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 287YM
UT WOS:000329578400001
PM 23688319
ER
PT J
AU Wilcox, MV
Carlson, VCC
Sherazee, N
Sprow, GM
Bock, R
Thiele, TE
Lovinger, DM
Alvarez, VA
AF Wilcox, Mark V.
Carlson, Verginia C. Cuzon
Sherazee, Nyssa
Sprow, Gretchen M.
Bock, Roland
Thiele, Todd E.
Lovinger, David M.
Alvarez, Veronica A.
TI Repeated Binge-Like Ethanol Drinking Alters Ethanol Drinking Patterns
and Depresses Striatal GABAergic Transmission
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE alcohol; drinking in the dark; dendritic spines; dopamine; striatum;
dorsolateral striatum
ID NUCLEUS-ACCUMBENS; ALCOHOL-DRINKING; C57BL/6J MICE; RECEPTOR FUNCTION;
DORSAL STRIATUM; DARK PROCEDURES; LONG-TERM; CONSUMPTION; COCAINE;
INTOXICATION
AB Repeated cycles of binge alcohol drinking and abstinence are key components in the development of dependence. However, the precise behavioral mechanisms underlying binge-like drinking and its consequences on striatal synaptic physiology remain unclear. In the present study, ethanol and water drinking patterns were recorded with high temporal resolution over 6 weeks of binge-like ethanol drinking using the 'drinking in the dark' (DID) protocol. The bottle exchange occurring at the beginning of each session prompted a transient increase in the drinking rate that might facilitate the acquisition of ethanol binge-like drinking. Ethanol drinking mice also displayed a 'front-loading' behavior, in which the highest rate of drinking was recorded during the first 15 min. This rate increased over weeks and paralleled the mild escalation of blood ethanol concentrations. GABAergic and glutamatergic transmission in the dorsal striatum were examined following DID. Spontaneous glutamatergic transmission and the density of dendritic spines were unchanged after ethanol drinking. However, the frequency of GABA(A) receptor-mediated inhibitory postsynaptic currents was depressed in medium spiny neurons of ethanol drinking mice. A history of ethanol drinking also increased ethanol preference and altered the acute ethanol effects on GABAergic transmission differentially in dorsolateral and dorsomedial striatum. Together, the study shows that the bottle exchange during DID promotes fast, voluntary ethanol drinking and that this intermittent pattern of ethanol drinking causes a depression of GABAergic transmission in the dorsal striatum.
C1 [Wilcox, Mark V.; Sherazee, Nyssa; Bock, Roland; Alvarez, Veronica A.] NIAAA, Sect Neuronal Struct, Bethesda, MD 20892 USA.
[Carlson, Verginia C. Cuzon; Lovinger, David M.] NIAAA, Sect Synapt Pharmacol, Bethesda, MD 20892 USA.
[Sprow, Gretchen M.; Thiele, Todd E.] Univ N Carolina, Dept Psychol, Chapel Hill, NC USA.
[Thiele, Todd E.] Univ N Carolina, Bowles Ctr Alcohol Studies, Bethesda, MD USA.
RP Alvarez, VA (reprint author), NIAAA, NIH, 5625 Fishers Lane, Bethesda, MD 20892 USA.
EM alvarezva@mail.nih.gov
RI Alvarez, Veronica /E-9745-2015; Bock, Roland/G-2982-2016
OI Alvarez, Veronica /0000-0003-2611-8675; Bock, Roland/0000-0002-8654-1080
FU Intramural Program of NIAAA [ZIA-AA000421]; Intramural Program of NINDS
[ZIA-AA000421]; NIH [AA013573, AA015148, AA019839]
FX We are grateful to Dr Fumihito Ono for the use of the confocal
microscope and to Paul Kramer and Dr Lee Chedester for assistance with
the cage modifications. Dr Matthew Pava and the members of the Alvarez
laboratory provided helpful comments on the manuscript. This study was
funded by the Intramural Programs of NIAAA and NINDS (ZIA-AA000421) to
VAA, the Intramural Programs of NIAAA for DML and by NIH grants
AA013573, AA015148, and AA019839 to TET.
NR 39
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U1 0
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD FEB
PY 2014
VL 39
IS 3
BP 579
EP 594
DI 10.1038/npp.2013.230
PG 16
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 291PZ
UT WOS:000329842600007
PM 23995582
ER
PT J
AU Bjork, JM
Grant, SJ
Chen, G
Hommer, DW
AF Bjork, James M.
Grant, Steven J.
Chen, Gang
Hommer, Daniel W.
TI Dietary Tyrosine/Phenylalanine Depletion Effects on Behavioral and Brain
Signatures of Human Motivational Processing
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE reward; dopamine; fMRI; striatum; tyrosine; behavior
ID AMINO-ACID MIXTURE; ACUTE TYROSINE DEPLETION; HEALTHY-VOLUNTEERS;
CATECHOLAMINE SYNTHESIS; REWARD ANTICIPATION; DOPAMINE; PHENYLALANINE;
AMPHETAMINE; DEPRESSION; INGESTION
AB Dopamine (DA) neurotransmission is critical for motivational processing. We assessed whether disruption of DA synthesis in healthy controls using an amino-acid beverage devoid of catecholamine precursors (tyrosine-phenylalanine depletion (TPD)) would blunt recruitment of the nucleus accumbens (NAcc) by rewards. Sixteen controls ingested each of a tyr/phe-depleting beverage (DEP) or a tyr/phe-balanced (BAL) control beverage in two laboratory visits. Five hours after consumption of each drink, subjects underwent functional magnetic resonance imaging while they viewed anticipatory cues to respond to a target to either win money or avoid losing money. TPD did not exert main effects on mood or on task behavior, but affected brain activation. In right NAcc, TPD blunted activation by anticipation of high rewards. In left NAcc, recruitment anticipating high rewards was modulated by individual differences in mood change across the DEP drink day, where subjects whose mood worsened following TPD (relative to within-day mood change under BAL conditions) also showed lower activation under DEP conditions relative to BAL conditions. Exploratory analysis indicated that TPD qualitatively blunted the voxel-wise spatial extent of suprathreshold activation by reward anticipation. Finally, loss outcomes activated anterior insula under DEP conditions but not under BAL conditions. These data indicate that: (1) dietary depletion of catacholamine precursors will blunt dopaminergic mesolimbic activity, and (2) in controls, synthetic pathways of this neurocircuitry maintain sufficient buffering capacity to resist an effect on motivated behavior. Additional studies are needed to determine if clinical populations would show similar resistance to behavioral effects of TPD.
C1 [Bjork, James M.; Grant, Steven J.] NIDA, Div Clin Neurosci & Behav Res, NIH, Bethesda, MD 20892 USA.
[Chen, Gang] NIMH, Sci & Stat Comp Core, NIH, Bethesda, MD 20892 USA.
[Hommer, Daniel W.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA.
RP Bjork, JM (reprint author), NIDA, Div Clin Neurosci & Behav Res, NIH, 6001 Execut Blvd,Room 3163, Bethesda, MD 20892 USA.
EM jbjork@mail.nih.gov
OI Bjork, James/0000-0003-0593-3291
FU National Institute on Alcohol Abuse and Alcoholism
FX This research was sponsored by intramural research funds of the National
Institute on Alcohol Abuse and Alcoholism. None of the authors has any
conflict or competing interest regarding this research study and its
findings, financial, or otherwise.
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U2 15
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PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD FEB
PY 2014
VL 39
IS 3
BP 595
EP 604
DI 10.1038/npp.2013.232
PG 10
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 291PZ
UT WOS:000329842600008
PM 23995581
ER
PT J
AU Leitl, MD
Onvani, S
Bowers, MS
Cheng, KJ
Rice, KC
Carlezon, WA
Banks, ML
Negus, S
AF Leitl, Michael D.
Onvani, Sara
Bowers, M. Scott
Cheng, Kejun
Rice, Kenner C.
Carlezon, William A., Jr.
Banks, Matthew L.
Negus, Stevens
TI Pain-Related Depression of the Mesolimbic Dopamine System in Rats:
Expression, Blockade by Analgesics, and Role of Endogenous kappa-opioids
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE dopamine; pain/analgesics; depression; nucleus accumbens; intracranial
self-stimulation; dynorphin
ID INTRACRANIAL SELF-STIMULATION; CONDITIONED PLACE AVERSION; FREELY MOVING
RATS; NUCLEUS-ACCUMBENS; PRECLINICAL ASSAYS; RECEPTOR AGONISTS;
SALVINORIN-A; BEHAVIOR; STRESS; ACTIVATION
AB Pain is often associated with depression of behavior and mood, and relief of pain-related depression is a common goal of treatment. This study tested the hypothesis that pain-related behavioral depression is mediated by activation of endogenous k-opioid systems and subsequent depression of mesolimbic dopamine release. Adult male Sprague-Dawley rats were implanted with electrodes targeting the medial forebrain bundle (for behavior studies of intracranial self-stimulation (ICSS)) or with cannulae for microdialysis measures of nucleus accumbens dopamine (NAc DA). Changes in ICSS and NAc DA were examined after treatment with a visceral noxious stimulus (intraperitoneal injection of dilute lactic acid) or an exogenous k-agonist (U69593). Additional studies examined the sensitivity of acid and U69593 effects to blockade by two analgesics (the nonsteroidal antiinflammatory drug ketoprofen and the m-opioid agonist morphine) or by the kappa-antagonist norbinaltorphimine (norBNI). The effects of acid were also examined on mRNA expression for prodynorphin (PDYN) and kappa-opioid receptors (KORs) in mesocorticolimbic brain regions. Both acid and U69593 depressed ICSS and extracellular levels of NAc DA. Pain-related acid effects were blocked by ketoprofen and morphine but not by norBNI. The U69593 effects were blocked by norBNI but not by ketoprofen, and were only attenuated by morphine. Acid did not significantly alter PDYN or KOR in NAc, but it produced a delayed increase in PDYN in prefrontal cortex. These results support a key role for the mesolimbic DA system, but a more nuanced role for endogenous k-opioid systems, in mediating acute pain-related behavioral depression in rats.
C1 [Leitl, Michael D.; Banks, Matthew L.; Negus, Stevens] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA.
[Onvani, Sara; Carlezon, William A., Jr.] Harvard Univ, McLean Hosp, Sch Med, Behav Genet Lab, Belmont, MA USA.
[Bowers, M. Scott] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23298 USA.
[Cheng, Kejun; Rice, Kenner C.] NIDA, Chem Biol Res Branch, Bethesda, MD 20892 USA.
[Cheng, Kejun; Rice, Kenner C.] NIAAA, NIH, Bethesda, MD USA.
RP Negus, S (reprint author), Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, 410 N 12th St,POB 980613, Richmond, VA 23298 USA.
EM ssnegus@vcu.edu
RI Banks, Matthew/K-4429-2014
OI Banks, Matthew/0000-0003-4949-5246
FU NIH; Alcohol Beverage Medical Research Foundation; National Institute on
Neurological Disorders and Stroke of the National Institutes of Health
[R01 NS070715]; Virginia Commonwealth University AD Williams Fund;
Intramural Research Programs of the National Institute on Drug Abuse;
National Institute on Alcohol Abuse and Alcoholism; [T32 DA007027]
FX Mr Leitl, Ms Onvani, and Drs Cheng, and Rice declare no conflict of
interest. Dr Bowers declares that his research has been funded by the
NIH and the Alcohol Beverage Medical Research Foundation. During the
past 3 years, he has not received any compensation from private or
publicly owned firms. Dr Carlezon declares that his research has been
funded by NIH. He has a US patent covering the use of kappa-antagonists
in the treatment of depressive disorders (Assignee: McLean Hospital). In
the past 3 years, Dr Carlezon has received compensation for professional
services from The American College of Neuropsychopharmacology and
Concert Pharmaceuticals. Dr Banks declares that his research has been
funded by NIH. During the past 3 years, he has received compensation as
a collaborator with the pharmaceutical companies Abbott and Purdue for
projects related to opioid pharmacology and analgesic drug development.
Dr Negus declares that his research has been funded by NIH. During the
past 3 years, he has received compensation as a consultant for or
collaborator with Abbott Pharmaceutical Company for projects related to
analgesic drug development. Research reported in this publication was
supported by the National Institute on Neurological Disorders and Stroke
of the National Institutes of Health under Award Numbers R01 NS070715.
In addition, Mr. Leitl was supported in part by T32 DA007027. Additional
funding was by the Virginia Commonwealth University AD Williams Fund,
and a portion of this work was also supported by the Intramural Research
Programs of the National Institute on Drug Abuse and the National
Institute on Alcohol Abuse and Alcoholism.
NR 51
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U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD FEB
PY 2014
VL 39
IS 3
BP 614
EP 624
DI 10.1038/npp.2013.236
PG 11
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 291PZ
UT WOS:000329842600010
PM 24008352
ER
PT J
AU Baladi, MG
Newman, AH
France, CP
AF Baladi, Michelle G.
Newman, Amy H.
France, Charles P.
TI Feeding condition and the relative contribution of different dopamine
receptor subtypes to the discriminative stimulus effects of cocaine in
rats
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE Cocaine; Dopamine D2 and D3 receptor subtype; Rats; Feeding condition;
PG01037; Drug discrimination
ID ADENYLATE-CYCLASE; SQUIRREL-MONKEYS; RHESUS-MONKEYS; EXTRACELLULAR
DOPAMINE; NUCLEUS-ACCUMBENS; (+)-PD 128907; D3 RECEPTOR; AGONISTS; D-3;
ANTAGONISTS
AB The contribution of dopamine receptor subtypes in mediating the discriminative stimulus effects of cocaine is not fully established. Many drug discrimination studies use food to maintain responding, necessitating food restriction, which can alter drug effects.
This study established stimulus control with cocaine (10 mg/kg) in free-feeding and food-restricted rats responding under a schedule of stimulus shock termination (SST) and in food-restricted rats responding under a schedule of food presentation to examine whether feeding condition or the reinforcer used to maintain responding impacts the effects of cocaine.
Dopamine receptor agonists and antagonists were examined for their ability to mimic or attenuate, respectively, the effects of cocaine.
Apomorphine, quinpirole, and lisuride occasioned > 90 % responding on the cocaine-associated lever in free-feeding rats responding under a schedule of SST; apomorphine, but not quinpirole or lisuride, occasioned > 90 % responding on the cocaine lever in food-restricted rats responding under a schedule of SST. In food-restricted rats responding for food these drugs occasioned little cocaine lever responding and were comparatively more potent in decreasing responding. In free-feeding rats, the effects of cocaine were attenuated by the D-2/D-3 receptor antagonist raclopride and the D-3 receptor-selective antagonist PG01037. In food-restricted rats, raclopride and the D-2 receptor-selective antagonist L-741,626 attenuated the effects of cocaine. Raclopride antagonized quinpirole in all groups while PG01037 antagonized quinpirole only in free-feeding rats.
These results demonstrate significant differences in the discriminative stimulus of cocaine that are due to feeding conditions and not to the use of different reinforcers across procedures.
C1 [Baladi, Michelle G.; France, Charles P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA.
[Newman, Amy H.] NIDA, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD USA.
[France, Charles P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA.
RP France, CP (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA.
EM france@uthscsa.edu
FU United States Public Health Service [K05DA17918]; National Institute on
Drug Abuse, National Institutes of Health
FX This work was supported by United States Public Health Service Grant
K05DA17918 (CPF), and the Intramural Research Program (AHN) National
Institute on Drug Abuse, National Institutes of Health. The content is
solely the responsibility of the authors and does not necessarily
represent the official views of the National Institute on Drug Abuse or
the National Institutes of Health.
NR 56
TC 4
Z9 4
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
EI 1432-2072
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD FEB
PY 2014
VL 231
IS 3
BP 581
EP 591
DI 10.1007/s00213-013-3271-x
PG 11
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 289HT
UT WOS:000329673300013
PM 24030470
ER
PT J
AU Martin-Marcos, P
Nanda, JS
Luna, RE
Zhang, F
Saini, AK
Cherkasova, VA
Wagner, G
Lorsch, JR
Hinnebusch, AG
AF Martin-Marcos, Pilar
Nanda, Jagpreet S.
Luna, Rafael E.
Zhang, Fan
Saini, Adesh K.
Cherkasova, Vera A.
Wagner, Gerhard
Lorsch, Jon R.
Hinnebusch, Alan G.
TI Enhanced eIF1 binding to the 40S ribosome impedes conformational
rearrangements of the preinitiation complex and elevates initiation
accuracy
SO RNA-A PUBLICATION OF THE RNA SOCIETY
LA English
DT Article
DE translation; initiation; eIF1; eIF2; ribosome; AUG recognition
ID EUKARYOTIC TRANSLATION INITIATION; START CODON SELECTION;
GUANINE-NUCLEOTIDE EXCHANGE; SACCHAROMYCES-CEREVISIAE; IN-VIVO;
MULTIFACTOR COMPLEX; YEAST; RECOGNITION; SUBUNIT; COMMUNICATION
AB In the current model of translation initiation by the scanning mechanism, eIF1 promotes an open conformation of the 40S subunit competent for rapidly loading the eIF2.GTP.Met-tRNAi ternary complex (TC) in a metastable conformation (POUT) capable of sampling triplets entering the P site while blocking accommodation of Met-tRNAi in the PIN state and preventing completion of GTP hydrolysis (P-i release) by the TC. All of these functions should be reversed by eIF1 dissociation from the preinitiation complex (PIC) on AUG recognition. We tested this model by selecting eIF1 Ssu(-) mutations that suppress the elevated UUG initiation and reduced rate of TC loading in vivo conferred by an eIF1 (Sui(-)) substitution that eliminates a direct contact of eIF1 with the 40S subunit. Importantly, several Ssu-substitutions increase eIF1 affinity for 40S subunits in vitro, and the strongest-binding variant (D61G), predicted to eliminate ionic repulsion with 18S rRNA, both reduces the rate of eIF1 dissociation and destabilizes the P-IN state of TC binding in reconstituted PICs harboring Sui(-) variants of eIF5 or eIF2. These findings establish that eIF1 dissociation from the 40S subunit is required for the PIN mode of TC binding and AUG recognition and that increasing eIF1 affinity for the 40S subunit increases initiation accuracy in vivo. Our results further demonstrate that the GTPase-activating protein eIF5 and beta-subunit of eIF2 promote accuracy by controlling eIF1 dissociation and the stability of TC binding to the PIC, beyond their roles in regulating GTP hydrolysis by eIF2.
C1 [Martin-Marcos, Pilar; Zhang, Fan; Saini, Adesh K.; Cherkasova, Vera A.; Hinnebusch, Alan G.] Eunice K Shriver Natl Inst Child Hlth & Human Dev, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA.
[Nanda, Jagpreet S.; Lorsch, Jon R.] Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA.
[Luna, Rafael E.; Wagner, Gerhard] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Saini, Adesh K.] Shoolini Univ Biotechnol & Management Sci, Dept Biotechnol, Solan 173212, Himachal Prades, India.
RP Lorsch, JR (reprint author), Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA.
EM jlorsch@jhmi.edu; ahinnebusch@nih.gov
RI university, shoolini/K-9336-2015;
OI Lorsch, Jon/0000-0002-4521-4999
FU Intramural Research Program of the NIH; NIH [GM62128, CA068262]
FX We thank Tom Dever for many helpful suggestions during the course of
this work. This study was supported in part by the Intramural Research
Program of the NIH (P.M.M., A.G.H.) and by NIH grants GM62128 (J.R.L.,
which supported J.S.N. and J.R.L.) and CA068262 (G.W., which supported
R.E.L.).
NR 39
TC 9
Z9 9
U1 0
U2 5
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1355-8382
EI 1469-9001
J9 RNA
JI RNA-Publ. RNA Soc.
PD FEB
PY 2014
VL 20
IS 2
BP 150
EP 167
DI 10.1261/rna.042069.113
PG 18
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 291ST
UT WOS:000329850500003
PM 24335188
ER
PT J
AU Thakur, M
Seo, EJ
Dever, TE
AF Thakur, Meghna
Seo, Eun Joo
Dever, Thomas E.
TI Variola virus E3L Z alpha domain, but not its Z-DNA binding activity, is
required for PKR inhibition
SO RNA-A PUBLICATION OF THE RNA SOCIETY
LA English
DT Article
DE E3L; PKR; eIF2; translation
ID DOUBLE-STRANDED-RNA; PROTEIN-KINASE PKR; N-TERMINAL DOMAIN; HANDED
Z-DNA; VACCINIA VIRUS; CRYSTAL-STRUCTURE; SUBSTRATE RECOGNITION;
GENE-PRODUCT; SACCHAROMYCES-CEREVISIAE; STRUCTURAL REQUIREMENTS
AB Responding to viral infection, the interferon-induced, double-stranded RNA (dsRNA)-activated protein kinase PKR phosphorylates translation initiation factor eIF2 alpha to inhibit cellular and viral protein synthesis. To overcome this host defense mechanism, many poxviruses express the protein E3L, containing an N-terminal Z-DNA binding (Z alpha) domain and a C-terminal dsRNA-binding domain (dsRBD). While E3L is thought to inhibit PKR activation by sequestering dsRNA activators and by directly binding the kinase, the role of the Z alpha domain in PKR inhibition remains unclear. Here, we show that the E3L Z alpha domain is required to suppress the growth-inhibitory properties associated with expression of human PKR in yeast, to inhibit PKR kinase activity in vitro, and to reverse the inhibitory effects of PKR on reporter gene expression in mammalian cells treated with dsRNA. Whereas previous studies revealed that the Z-DNA binding activity of E3L is critical for viral pathogenesis, we identified point mutations in E3L that functionally uncouple Z-DNA binding and PKR inhibition. Thus, our studies reveal a molecular distinction between the nucleic acid binding and PKR inhibitory functions of the E3L Z alpha domain, and they support the notion that E3L contributes to viral pathogenesis by targeting PKR and other components of the cellular anti-viral defense pathway.
C1 [Thakur, Meghna; Seo, Eun Joo; Dever, Thomas E.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA.
RP Dever, TE (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA.
EM tdever@nih.gov
OI Dever, Thomas/0000-0001-7120-9678
FU Intramural Research Program of the National Institutes of Health, NICHD
FX We thank members of the Dever and Hinnebusch laboratories for helpful
discussions. This work was supported by the Intramural Research Program
of the National Institutes of Health, NICHD.
NR 71
TC 3
Z9 3
U1 1
U2 6
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1355-8382
EI 1469-9001
J9 RNA
JI RNA-Publ. RNA Soc.
PD FEB
PY 2014
VL 20
IS 2
BP 214
EP 227
DI 10.1261/rna.042341.113
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 291ST
UT WOS:000329850500008
PM 24335187
ER
PT J
AU Greig, NH
Tweedie, D
Rachmany, L
Li, YZ
Rubovitch, V
Schreiber, S
Chiang, YH
Hoffer, BJ
Miller, J
Lahiri, DK
Sambamurti, K
Becker, RE
Pick, CG
AF Greig, Nigel H.
Tweedie, David
Rachmany, Lital
Li, Yazhou
Rubovitch, Vardit
Schreiber, Shaul
Chiang, Yung-Hsiao
Hoffer, Barry J.
Miller, Jonathan
Lahiri, Debomoy K.
Sambamurti, Kumar
Becker, Robert E.
Pick, Chaim G.
TI Incretin mimetics as pharmacologic tools to elucidate and as a new drug
strategy to treat traumatic brain injury
SO ALZHEIMERS & DEMENTIA
LA English
DT Article
ID GLUCAGON-LIKE PEPTIDE-1; TYPE-2 DIABETES-MELLITUS; FOCAL
CEREBRAL-ISCHEMIA; MESENCHYMAL STEM-CELLS; CENTRAL-NERVOUS-SYSTEM;
ALZHEIMERS-DISEASE; GLP-1 RECEPTOR; AMYLOID-BETA; PARKINSONS-DISEASE;
DENTATE GYRUS
AB Traumatic brain injury (TBI), either as an isolated injury or in conjunction with other injuries, is an increasingly common event. An estimated 1.7 million injuries occur within the USA each year and 10 million people are affected annually worldwide. Indeed, nearly one third (30.5%) of all injury-related deaths in the USA are associated with TBI, which will soon outpace many common diseases as the major cause of death and disability. Associated with a high morbidity and mortality and no specific therapeutic treatment, TBI has become a pressing public health and medical problem. The highest incidence of TBI occurs in young adults (15-24 years age) and in the elderly (>= 75 years of age). Older individuals are particularly vulnerable to these types of injury, often associated with falls, and have shown increased mortality and worse functional outcome after lower initial injury severity. In addition, a new and growing form of TBI, blast injury, associated with the detonation of improvised explosive devices in the war theaters of Iraq and Afghanistan, are inflicting a wave of unique casualties of immediate impact to both military personnel and civilians, for which long-term consequences remain unknown and may potentially be catastrophic. The neuropathology underpinning head injury is becoming increasingly better understood. Depending on severity, TBI induces immediate neuropathologic effects that, for the mildest form, may be transient; however, with increasing severity, these injuries cause cumulative neural damage and degeneration. Even with mild TBI, which represents the majority of cases, a broad spectrum of neurologic deficits, including cognitive impairments, can manifest that may significantly influence quality of life. Further, TBI can act as a conduit to longer term neurodegenerative disorders. Prior studies of glucagon-like peptide-1 (GLP-1) and long-acting GLP-1 receptor agonists have demonstrated neurotrophic/neuroprotective activities across a broad spectrum of cellular and animal models of chronic neurodegenerative (Alzheimer's and Parkinson's diseases) and acute cerebrovascular (stroke) disorders. In view of the mechanisms underpinning these disorders as well as TBI, we review the literature and recent studies assessing GLP-1 receptor agonists as a potential treatment strategy for mild to moderate TBI. (C) 2014 The Alzheimer's Association. All rights reserved.
C1 [Greig, Nigel H.; Tweedie, David; Li, Yazhou; Becker, Robert E.] NIA, Drug Design & Dev Sect, Translat Gerontol Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
[Rachmany, Lital; Rubovitch, Vardit; Pick, Chaim G.] Tel Aviv Univ, Sackler Sch Med, Dept Anat & Anthropol, IL-69978 Tel Aviv, Israel.
[Rachmany, Lital; Rubovitch, Vardit; Pick, Chaim G.] Tel Aviv Univ, Sagol Sch Neurosci, IL-69978 Tel Aviv, Israel.
[Schreiber, Shaul] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Dept Psychiat, IL-69978 Tel Aviv, Israel.
[Schreiber, Shaul] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel.
[Chiang, Yung-Hsiao] Taipei Med Univ Hosp, Dept Neurosurg, Taipei, Taiwan.
[Chiang, Yung-Hsiao] Taipei Med Univ, Grad Inst Neural Regenerat Med, Taipei, Taiwan.
[Hoffer, Barry J.; Miller, Jonathan] Case Western Reserve Univ, Sch Med, Dept Neurosurg, Cleveland, OH USA.
[Lahiri, Debomoy K.] Indiana Univ Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA.
[Sambamurti, Kumar] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA.
[Becker, Robert E.] Aristea Translat Med, Park City, UT USA.
RP Greig, NH (reprint author), NIA, Drug Design & Dev Sect, Translat Gerontol Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
EM greign@grc.nia.nih.gov
OI Schreiber, Shaul/0000-0002-2189-0693
FU National Institute on Aging, National Institutes of Health; Michael J.
Fox Foundation; Sackler School of Medicine, Tel-Aviv University; Israeli
Science Foundation [108/09]; Alzheimer's Association [IIRG 10-173-180
IIRG 10-173180, IIRG-11-206418]; National Institute on Aging [AG022103
R21AG046200, AG18379, AG18884, AG42804]; Lincoln Scholar Award; Taiwan
NSC [98-2321-B-038-002-MY3]
FX N.H.G., D.T., and Y.L. were supported by the Intramural Research
Program, National Institute on Aging, National Institutes of Health, and
in part by the Michael J. Fox Foundation. C.G.P., L.R., and V.R. were
supported by the Sackler School of Medicine, Tel-Aviv University, and in
part by a grant from the Israeli Science Foundation (108/09). K.S.
received grant support from the Alzheimer's Association (IIRG 10-173-180
IIRG 10-173180) and the National Institute on Aging (AG022103
R21AG046200). D.K.L. received grant support from the National Institute
on Aging (AG18379, AG18884 and AG42804) and Alzheimer's Association
(IIRG-11-206418). J.M. was supported by the Lincoln Scholar Award and
Y.-H.C. was supported by Taiwan NSC (98-2321-B-038-002-MY3). R.E.B. is
President of Aristea Translational Medicine Corp., but has received no
support in relation to this article.
NR 184
TC 20
Z9 20
U1 2
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1552-5260
EI 1552-5279
J9 ALZHEIMERS DEMENT
JI Alzheimers. Dement.
PD FEB
PY 2014
VL 10
SU 1
BP S62
EP S75
DI 10.1016/j.jalz.2013.12.011
PG 14
WC Clinical Neurology
SC Neurosciences & Neurology
GA CN6OW
UT WOS:000358555100009
PM 24529527
ER
PT J
AU Adeyemo, A
AF Adeyemo, A.
TI Genetics of type II diabetes in populations of African ancestry
SO DIABETES RESEARCH AND CLINICAL PRACTICE
LA English
DT Meeting Abstract
C1 [Adeyemo, A.] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0168-8227
EI 1872-8227
J9 DIABETES RES CLIN PR
JI Diabetes Res. Clin. Pract.
PD FEB
PY 2014
VL 103
SU 1
MA I.3
BP S2
EP S2
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V43TE
UT WOS:000209702900004
ER
PT J
AU Gnani, D
Vella, S
Crudele, A
Ceccarelli, S
De Stefanis, C
Gaspari, S
Nobili, V
Locatelli, F
Marquez, VE
Rota, R
Alisi, A
AF Gnani, D.
Vella, S.
Crudele, A.
Ceccarelli, S.
De Stefanis, C.
Gaspari, S.
Nobili, V.
Locatelli, F.
Marquez, V. E.
Rota, R.
Alisi, A.
TI ENHANCER OF ZESTE HOMOLOG 2 (EZH2) EXPRESSION AND ACTIVATION IN IN VIVO
AND IN VITRO NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD)
SO DIGESTIVE AND LIVER DISEASE
LA English
DT Meeting Abstract
C1 [Gnani, D.; Crudele, A.; Ceccarelli, S.; De Stefanis, C.; Nobili, V.; Alisi, A.] IRCCS, Bambino Gesu Childrens Hosp, Liver Res Unit, Rome, Italy.
[Vella, S.; Gaspari, S.; Locatelli, F.; Rota, R.] IRCCS, Bambino Gesu Childrens Hosp, Dept Oncohematol, Rome, Italy.
[Marquez, V. E.] NCI, Biol Chem Lab, Frederick Natl Lab Canc Res,CCR, NIH, Frederick, MD 21701 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 1590-8658
EI 1878-3562
J9 DIGEST LIVER DIS
JI Dig. Liver Dis.
PD FEB
PY 2014
VL 46
SU 1
MA T-25
BP E28
EP E28
DI 10.1016/j.dld.2014.01.065
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA V45OY
UT WOS:000209827100060
ER
PT J
AU Barnes, A
Perosky, J
Rajpar, MH
Kozloff, K
Marini, J
AF Barnes, Aileen
Perosky, Joseph
Rajpar, M. Helen
Kozloff, Kenneth
Marini, Joan
TI Mouse Model with Mutant Type I Collagen C-propeptide Cleavage Site has
Brittle Bones and Increased Osteoblast Mineralization
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research
CY SEP 12-15, 2014
CL Houston, TX
SP Amer Soc Bone & Mineral Res
C1 [Barnes, Aileen; Rajpar, M. Helen] NICHD, NIH, Bethesda, MD USA.
[Perosky, Joseph] Univ Michigan, Ann Arbor, MI 48109 USA.
[Kozloff, Kenneth] Univ Michigan, Dept Orthopaed Surg, Ann Arbor, MI 48109 USA.
[Marini, Joan] NICHHD, Bethesda, MD USA.
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 0884-0431
EI 1523-4681
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD FEB
PY 2014
VL 29
SU 1
MA SU0122
BP S247
EP S247
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CK9ZS
UT WOS:000356598701433
ER
PT J
AU Barton, D
Sinder, B
Yang, YC
Marini, J
Caird, M
Kozloff, K
AF Barton, David
Sinder, Benjamin
Yang, Yuchen
Marini, Joan
Caird, Michelle
Kozloff, Kenneth
TI Dose response study of the effects of sclerostin antibody on cortical
bone mass and strength in Brtl/ plus mouse.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research
CY SEP 12-15, 2014
CL Houston, TX
SP Amer Soc Bone & Mineral Res
C1 [Barton, David; Sinder, Benjamin; Yang, Yuchen; Caird, Michelle] Univ Michigan, Ann Arbor, MI 48109 USA.
[Marini, Joan] NICHHD, Bethesda, MD USA.
[Kozloff, Kenneth] Univ Michigan, Dept Orthopaed Surg, Ann Arbor, MI 48109 USA.
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 0884-0431
EI 1523-4681
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD FEB
PY 2014
VL 29
SU 1
MA SU0168
BP S260
EP S261
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CK9ZS
UT WOS:000356598701477
ER
PT J
AU Bhattacharyya, N
Kucka, M
Chen, CZ
Hu, X
Southall, NT
Estrada, A
Collins, MT
AF Bhattacharyya, Nisan
Kucka, Marek
Chen, Catherine Z.
Hu, Xin
Southall, Noel T.
Estrada, Andrea
Collins, Michael T.
TI Characterization of small molecule activators and inhibitors of the
mutated G(s)alpha responsible for Fibrous Dysplasia of Bone.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research
CY SEP 12-15, 2014
CL Houston, TX
SP Amer Soc Bone & Mineral Res
C1 [Bhattacharyya, Nisan; Collins, Michael T.] NIDCR, NIH, Bethesda, MD USA.
[Kucka, Marek] NICHD, NIH, Bethesda, MD USA.
[Chen, Catherine Z.; Hu, Xin; Southall, Noel T.] NIH, NCATS, Bethesda, MD USA.
[Estrada, Andrea] NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0884-0431
EI 1523-4681
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD FEB
PY 2014
VL 29
SU 1
MA MO0128
BP S389
EP S389
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CK9ZS
UT WOS:000356598702281
ER
PT J
AU Bryant, H
Benson, C
Krishnan, V
Sato, M
Cain, R
Zeng, QQ
Robins, D
Yang, N
Ma, YF
AF Bryant, Henry
Benson, Charles
Krishnan, Venkatesh
Sato, Masahiko
Cain, Ricky
Zeng, Qianqiang
Robins, Deborah
Yang, Nora
Ma, Yanfei
TI Evolution of a Long-Acting Parathyroid Hormone Analog for the Treatment
of Hypoparathyroidism.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research
CY SEP 12-15, 2014
CL Houston, TX
SP Amer Soc Bone & Mineral Res
C1 [Bryant, Henry; Benson, Charles; Krishnan, Venkatesh; Cain, Ricky; Zeng, Qianqiang; Robins, Deborah; Ma, Yanfei] Eli Lilly & Co, Indianapolis, IN 46285 USA.
[Sato, Masahiko] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
[Yang, Nora] NIH, Therapeut Rare & Neglected Dis, Natl Ctr Adv Translat Sci, New York, NY USA.
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 0884-0431
EI 1523-4681
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD FEB
PY 2014
VL 29
SU 1
MA MO0137
BP S391
EP S391
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CK9ZS
UT WOS:000356598702290
ER
PT J
AU Burke, A
Wang, H
Tsai, J
Bhattacharyya, N
Boyce, A
Gafni, R
Estrada, A
Molinolo, A
Robey, P
Collins, M
AF Burke, Andrea
Wang, Howard
Tsai, Jeffrey
Bhattacharyya, Nisan
Boyce, Alison
Gafni, Rachel
Estrada, Andrea
Molinolo, Alfredo
Robey, Pamela
Collins, Michael
TI RANKL Inhibition in the Pathogenesis and Treatment of Fibrous Dysplasia.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research
CY SEP 12-15, 2014
CL Houston, TX
SP Amer Soc Bone & Mineral Res
C1 [Burke, Andrea; Bhattacharyya, Nisan; Gafni, Rachel; Estrada, Andrea; Molinolo, Alfredo; Collins, Michael] NIH, Bethesda, MD USA.
[Wang, Howard] Univ Maryland, Baltimore, MD USA.
[Tsai, Jeffrey] SUNY Buffalo, Buffalo, NY 14260 USA.
[Boyce, Alison] Childrens Natl Med Ctr, Washington, DC USA.
[Robey, Pamela] Natl Inst Dent & Craniofacial Res, Bethesda, MD USA.
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 0884-0431
EI 1523-4681
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD FEB
PY 2014
VL 29
SU 1
MA FR0433
BP S119
EP S119
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CK9ZS
UT WOS:000356598701051
ER
PT J
AU Cabral, W
Makareeva, E
Ishikawa, M
Barnes, A
Weis, M
Lacbawan, F
Eyre, D
Yamada, Y
Leikin, S
Marini, J
AF Cabral, Wayne
Makareeva, Elena
Ishikawa, Masaki
Barnes, Aileen
Weis, MaryAnn
Lacbawan, Felicitas
Eyre, David
Yamada, Yoshihiko
Leikin, Sergey
Marini, Joan
TI Absence of ER cation channel TMEM38B/TRIC-B causes recessive
osteogenesis imperfecta by dysregulation of collagen post-translational
modification
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research
CY SEP 12-15, 2014
CL Houston, TX
SP Amer Soc Bone & Mineral Res
C1 [Cabral, Wayne; Barnes, Aileen] NICHD, Bone & Extracellular Matrix Branch, NIH, Washington, DC USA.
[Makareeva, Elena] NICHD, Sect Phys Biochem, NIH, Washington, DC USA.
[Ishikawa, Masaki; Yamada, Yoshihiko] NIDCR, Mol Biol Sect, NIH, Washington, DC USA.
[Weis, MaryAnn] Univ Washington, Dept Orthopaed & Sports Med, Seattle, WA 98195 USA.
[Lacbawan, Felicitas] Childrens Natl Med Ctr, Dept Med Genet, Washington, DC USA.
[Eyre, David] Univ Washington, Orthopaed Res Labs, Seattle, WA 98195 USA.
[Leikin, Sergey] NIH, New York, NY USA.
[Marini, Joan] NICHHD, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0884-0431
EI 1523-4681
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD FEB
PY 2014
VL 29
SU 1
MA 1095
BP S32
EP S32
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CK9ZS
UT WOS:000356598700096
ER
PT J
AU Carballido-Gamio, J
Bonaretti, S
Saeed, I
Harnish, R
Recker, R
Burghardt, A
Keyak, J
Harris, T
Khosla, S
Lang, T
AF Carballido-Gamio, Julio
Bonaretti, Serena
Saeed, Isra
Harnish, Roy
Recker, Robert
Burghardt, Andrew
Keyak, Joyce
Harris, Tamara
Khosla, Sundeep
Lang, Thomas
TI Automatic QCT quantification of the proximal femur: vBMD, bone volume,
cortical bone thickness and finite element modeling
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research
CY SEP 12-15, 2014
CL Houston, TX
SP Amer Soc Bone & Mineral Res
C1 [Carballido-Gamio, Julio; Bonaretti, Serena; Saeed, Isra; Harnish, Roy; Burghardt, Andrew; Lang, Thomas] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Recker, Robert] Creighton Univ, Omaha, NE 68178 USA.
[Keyak, Joyce] Univ Calif Irvine, Dept Radiol Sci, Irvine, CA 92717 USA.
[Harris, Tamara] NIA, Intramural Res Program, Bethesda, MD 20892 USA.
[Khosla, Sundeep] Mayo Clin, Coll Med, Rochester, MN USA.
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 0884-0431
EI 1523-4681
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD FEB
PY 2014
VL 29
SU 1
MA FR0286
BP S94
EP S95
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CK9ZS
UT WOS:000356598700294
ER
PT J
AU De Castro, LF
Bodhak, S
Kuznetsov, S
Kilts, T
Young, M
Lin-Gibson, S
Simon, C
Robey, P
AF Fernandez De Castro, Luis
Bodhak, Subdhadip
Kuznetsov, Sergei
Kilts, Tina
Young, Marian
Lin-Gibson, Sheng
Simon, Carl
Robey, Pamela
TI Combinatorial cassettes, a high-throughout approach for the assessment
of bone formation in vivo.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research
CY SEP 12-15, 2014
CL Houston, TX
SP Amer Soc Bone & Mineral Res
C1 [Fernandez De Castro, Luis] NIDCR NIH, Seville, Spain.
[Bodhak, Subdhadip; Lin-Gibson, Sheng; Simon, Carl] NIST, Gaithersburg, MD USA.
[Kuznetsov, Sergei; Kilts, Tina; Young, Marian] NIH, Bethesda, MD USA.
[Robey, Pamela] Natl Inst Dent & Craniofacial Res, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0884-0431
EI 1523-4681
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD FEB
PY 2014
VL 29
SU 1
MA SA0038
BP S136
EP S136
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CK9ZS
UT WOS:000356598701100
ER
PT J
AU Hall, M
Perantoni, A
AF Hall, Michael
Perantoni, Alan
TI Stat3 signaling modulates the osteochondro transcription factor Sox9 in
vivo to influence endochondral ossification and is important in the
pathology of campomelic dysplasia.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research
CY SEP 12-15, 2014
CL Houston, TX
SP Amer Soc Bone & Mineral Res
C1 [Hall, Michael; Perantoni, Alan] NCI, Bethesda, MD 20892 USA.
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 0884-0431
EI 1523-4681
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD FEB
PY 2014
VL 29
SU 1
MA SU0469
BP S351
EP S351
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CK9ZS
UT WOS:000356598702156
ER
PT J
AU Horton, J
Degheidy, H
Bauer, S
Robey, P
Holmbeck, K
AF Horton, Jason
Degheidy, Heba
Bauer, Steven
Robey, Pamela
Holmbeck, Kenn
TI Regulation of skeletal stem cell multipotency by MT1-MMP.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research
CY SEP 12-15, 2014
CL Houston, TX
SP Amer Soc Bone & Mineral Res
C1 [Horton, Jason] NCI, NIH, Bethesda, MD 20892 USA.
[Degheidy, Heba; Bauer, Steven] US FDA, Lab Stem Cell Biol, Div Cell & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA.
[Robey, Pamela; Holmbeck, Kenn] Natl Inst Dent & Craniofacial Res, New York, NY USA.
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 0884-0431
EI 1523-4681
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD FEB
PY 2014
VL 29
SU 1
MA SA0249
BP S169
EP S169
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CK9ZS
UT WOS:000356598701201
ER
PT J
AU Hsu, YH
Estrada, K
Leo, P
Teumer, A
Liu, CT
Duncan, E
Zheng, HF
Minster, R
Lyytikainen, LP
Amin, N
Pengelly, R
Guerrero, RC
Marc, J
Nielson, C
Yerges-Armstrong, L
Claussnitzer, M
Oei, L
van Schoor, NM
Medina-Gomez, C
Zhou, YH
Cheng, CH
Liu, YM
Volker, U
Kahonen, M
Cooper, C
Uitterlinden, A
Hannemann, A
Karasik, D
Mencej-Bedrac, S
Moral, JAR
Holloway, J
Lehtimaki, T
Jackson, R
Cupples, LA
Harris, T
Wallaschofski, H
Rivadeneira, F
Richards, B
Chasman, D
Brown, M
Kiel, D
AF Hsu, Yi-Hsiang
Estrada, Karol
Leo, Paul
Teumer, Alexander
Liu, Ching-Ti
Duncan, Emma
Zheng, HouFeng
Minster, Ryan
Lyytikainen, Leo-Pekka
Amin, Najaf
Pengelly, Ruben
Cruz Guerrero, Raquel
Marc, Janja
Nielson, Carrie
Yerges-Armstrong, Laura
Claussnitzer, Melina
Oei, Ling
van Schoor, N. M.
Medina-Gomez, Carolina
Zhou, Yanhua
Cheng, Chao-Ho
Liu, Yongmei
Voelker, Uwe
Kahonen, Mika
Cooper, Cyrus
Uitterlinden, Andre
Hannemann, Anke
Karasik, David
Mencej-Bedrac, Simona
Riancho Moral, Jose Antonio
Holloway, John
Lehtimaki, Terho
Jackson, Rebecca
Cupples, L. Adrienne
Harris, Tamara
Wallaschofski, Henri
Rivadeneira, Fernando
Richards, Brent
Chasman, Daniel
Brown, Matthew
Kiel, Douglas
TI Rare Protein-Coding Variants Are Associated with Osteoporotic Fracture:
An Exome-Chip Analysis of 44,130 Adult Caucasians in CHARGE and GEFOS
Consortia.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research
CY SEP 12-15, 2014
CL Houston, TX
SP Amer Soc Bone & Mineral Res
C1 [Hsu, Yi-Hsiang; Claussnitzer, Melina; Cheng, Chao-Ho] Hebrew SeniorLife, Inst Aging Res, Roslindale, MA USA.
[Hsu, Yi-Hsiang; Claussnitzer, Melina; Chasman, Daniel] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Estrada, Karol] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
[Leo, Paul] Univ Queensland, Diamantina Inst, Brisbane, Qld, Australia.
[Teumer, Alexander; Voelker, Uwe] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany.
[Liu, Ching-Ti; Cupples, L. Adrienne] Boston Univ, Dept Biostat, Boston, MA 02215 USA.
[Duncan, Emma] Royal Brisbane & Womens Hosp, Brisbane, Qld, Australia.
[Zheng, HouFeng] McGill Univ, Dept Med, Montreal, PQ H3A 2T5, Canada.
[Zheng, HouFeng] McGill Univ, Dept Human Genet, Montreal, PQ H3A 2T5, Canada.
[Zheng, HouFeng] McGill Univ, Dept Epidemiol, Montreal, PQ H3A 2T5, Canada.
[Zheng, HouFeng] McGill Univ, Dept Biostat, Montreal, PQ H3A 2T5, Canada.
[Minster, Ryan] Univ Pittsburgh, Dept Human Genet & Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA.
[Lyytikainen, Leo-Pekka; Lehtimaki, Terho] Fimlab Labs, Dept Clin Chem, Helsinki, Finland.
[Amin, Najaf] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Pengelly, Ruben; Holloway, John] Univ Southampton, Fac Med, Human Genet & Genom Med, Southampton SO9 5NH, Hants, England.
[Cruz Guerrero, Raquel] Univ Santiago de Compostela, La Coruna, Spain.
[Marc, Janja] Univ Ljubljana, Div Clin Biochem, Ljubljana 61000, Slovenia.
[Nielson, Carrie] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Yerges-Armstrong, Laura] Univ Maryland, Sch Med, Baltimore, MD USA.
[Oei, Ling; Rivadeneira, Fernando] Erasmus Univ, Med Ctr, NL-3000 DR Rotterdam, Netherlands.
[van Schoor, N. M.] EMGO Inst Hlth & Care Res, Dept Epidemiol & Biostat, Rotterdam, Netherlands.
[Medina-Gomez, Carolina] Erasmus MC, Rotterdam, Netherlands.
[Zhou, Yanhua] Boston Univ, Boston, MA 02215 USA.
[Liu, Yongmei] Wake Forest Sch Med, Ctr Human Genet, Div Publ Hlth Sci, Winston Salem, NC USA.
[Kahonen, Mika] Univ Tampere, Sch Med, Dept Clin Physiol, FIN-33101 Tampere, Finland.
[Cooper, Cyrus] Univ Southampton, Southampton SO9 5NH, Hants, England.
[Hannemann, Anke] Univ Med, Inst Clin Chem & Lab Med, Berlin, Germany.
[Karasik, David; Kiel, Douglas] Hebrew SeniorLife, New York, NY USA.
[Karasik, David] Bar Ilan Univ, New York, NY USA.
[Mencej-Bedrac, Simona] Univ Ljubljana, Fac Pharm, Ljubljana 61000, Slovenia.
[Riancho Moral, Jose Antonio] Univ Cantabria, Hosp UM Valdecilla IFIMAV, Santander, Spain.
[Jackson, Rebecca] Ohio State Univ, Columbus, OH 43210 USA.
[Harris, Tamara] NIA, Intramural Res Program, Bethesda, MD 20892 USA.
[Wallaschofski, Henri] Ernst Moritz Arndt Univ Greifswald, Univ Med Greifswald, Inst Clin Chem & Lab Med, Inst Community Med, Greifswald, Germany.
[Richards, Brent] McGill Univ, Montreal, PQ H3A 2T5, Canada.
[Chasman, Daniel] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Brown, Matthew] Diamantina Inst Canc Immunol & Metab Med, Sydney, NSW, Australia.
RI Oei, Ling/E-8163-2013
OI Oei, Ling/0000-0003-3523-458X
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 0884-0431
EI 1523-4681
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD FEB
PY 2014
VL 29
SU 1
MA 1027
BP S10
EP S11
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CK9ZS
UT WOS:000356598700028
ER
PT J
AU Kiel, D
Broe, K
Cupples, A
Demissie, S
Fox, C
Hannan, M
Hsu, YH
Karasik, D
Liu, CT
McLean, R
Meng, CA
Samelson, E
Zhang, XC
Bouxsein, M
AF Kiel, Douglas
Broe, Kerry
Cupples, Adrienne
Demissie, Serkalem
Fox, Caroline
Hannan, Marian
Hsu, Yi-Hsiang
Karasik, David
Liu, Ching-Ti
McLean, Robert
Meng, Ching-An
Samelson, Elizabeth (Lisa)
Zhang, Xiaochun
Bouxsein, Mary
TI Visceral Adipose Tissue is Associated with Better Trabecular Density and
Architecture but Increased Cortical Porosity: The Framingham
Osteoporosis Study.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research
CY SEP 12-15, 2014
CL Houston, TX
SP Amer Soc Bone & Mineral Res
C1 [Kiel, Douglas; Karasik, David] Hebrew SeniorLife, Roslindale, MA USA.
[Broe, Kerry] Inst Aging ResearchHebrew SeniorLife, Boston, MA USA.
[Cupples, Adrienne; Demissie, Serkalem; Liu, Ching-Ti] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA.
[Fox, Caroline] NIH, Bethesda, MD USA.
[Hannan, Marian] HSL Inst Aging Res, Boston, MA USA.
[Hannan, Marian; Hsu, Yi-Hsiang; McLean, Robert] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Hsu, Yi-Hsiang; McLean, Robert] Hebrew SeniorLife Inst Aging Res, Boston, MA USA.
[Meng, Ching-An; Zhang, Xiaochun] Hebrew SeniorLife, Inst Aging Res, Boston, MA USA.
[Samelson, Elizabeth (Lisa)] Harvard Univ, Sch Med, Hebrew SeniorLife, Cambridge, MA 02138 USA.
[Bouxsein, Mary] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Cambridge, MA 02138 USA.
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 0884-0431
EI 1523-4681
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD FEB
PY 2014
VL 29
SU 1
MA FR0338
BP S102
EP S102
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CK9ZS
UT WOS:000356598701004
ER
PT J
AU Kim, HN
Bartell, S
Han, L
Warren, A
Iyer, S
de Cabo, R
Manolagas, S
Almeida, MJ
AF Kim, Ha-Neui
Bartell, Shoshana
Han, Li
Warren, Aaron
Iyer, Srividhya
de Cabo, Rafael
Manolagas, Stavros
Almeida, Maria Jose
TI Sirtuin 1 suppresses mitochondrial ATP and osteoclastogenesis via
FoxO-mediated stimulation of Heme oxygenase 1
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research
CY SEP 12-15, 2014
CL Houston, TX
SP Amer Soc Bone & Mineral Res
C1 [Kim, Ha-Neui; Bartell, Shoshana; Han, Li; Iyer, Srividhya; Manolagas, Stavros; Almeida, Maria Jose] Univ Arkansas Med Sci, Cent Arkansas VA Healthcare Syst, Little Rock, AR 72205 USA.
[Warren, Aaron] Univ Arkansas Med Sci, Ctr Osteoporosis & Metab Bone Dis, Little Rock, AR 72205 USA.
[Warren, Aaron] Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA.
[de Cabo, Rafael] NIA, Translat Gerontol Branch, NIH, Bethesda, MD 20892 USA.
RI de Cabo, Rafael/J-5230-2016
OI de Cabo, Rafael/0000-0002-3354-2442
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0884-0431
EI 1523-4681
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD FEB
PY 2014
VL 29
SU 1
MA FR0269
BP S92
EP S92
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CK9ZS
UT WOS:000356598700285
ER
PT J
AU Kram, V
Kilts, T
Holmbeck, K
Young, M
AF Kram, Vardit
Kilts, Tina
Holmbeck, Kenn
Young, Marian
TI Biglycan and fibromodulin deficiency leads to increased bone remodeling
that can be rescued by exogenous osteoprotegerin.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research
CY SEP 12-15, 2014
CL Houston, TX
SP Amer Soc Bone & Mineral Res
C1 [Kram, Vardit; Young, Marian] NIH, Bethesda, MD USA.
[Kilts, Tina; Holmbeck, Kenn] NIDCR, NIH, Bethesda, MD USA.
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 0884-0431
EI 1523-4681
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD FEB
PY 2014
VL 29
SU 1
MA MO0181
BP S405
EP S405
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CK9ZS
UT WOS:000356598702332
ER
PT J
AU Lang, T
Sigurdsson, S
Sigurdsson, G
Siggeirsdottir, K
Gudnason, V
Harris, T
AF Lang, Thomas
Sigurdsson, Sigurdur
Sigurdsson, Gunnar
Siggeirsdottir, Kristin
Gudnason, Vilmundur
Harris, Tamara
TI Muscle mass and adiposity, muscle strength, and physical performance
vary by gender as risk factors for hip fracture: the Age
Gene/Environment Susceptibility Study-Reykjavik
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research
CY SEP 12-15, 2014
CL Houston, TX
SP Amer Soc Bone & Mineral Res
C1 [Lang, Thomas] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Sigurdsson, Sigurdur; Siggeirsdottir, Kristin] Iceland Heart Assoc, Reykjavik, Iceland.
[Sigurdsson, Gunnar] Landspitali, Reykjavik, Iceland.
[Gudnason, Vilmundur] Iceland Heart Assoc, Res Inst, Reykjavik, Iceland.
[Harris, Tamara] NIA, Intramural Res Program, Bethesda, MD 20892 USA.
RI Gudnason, Vilmundur/K-6885-2015
OI Gudnason, Vilmundur/0000-0001-5696-0084
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0884-0431
EI 1523-4681
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD FEB
PY 2014
VL 29
SU 1
MA MO0446
BP S489
EP S489
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CK9ZS
UT WOS:000356598702591
ER
PT J
AU Liu, HH
Qi, B
Cong, Q
Li, P
Schneider, M
Li, BJ
AF Liu, Huihuan
Qi, Bing
Cong, Qian
Li, Ping
Schneider, Micheal
Li, Baojie
TI Ablation of Tak1 in monocyte leads to defects in skeletal growth and
bone remodeling in mice.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research
CY SEP 12-15, 2014
CL Houston, TX
SP Amer Soc Bone & Mineral Res
C1 [Liu, Huihuan; Cong, Qian; Li, Ping] Shanghai Jiao Tong Univ, Minist Educ, Key Lab Genet Dev & Neuropsychiat Disorders, Bio X Inst, Shanghai 200030, Peoples R China.
[Qi, Bing] Taishan Med Univ, Sch Biol Sci, Taishan, Peoples R China.
[Schneider, Micheal] Natl Heart & Lung Inst, Cardiovasc Sci, Bethesda, MD USA.
[Li, Baojie] Shanghai Jiao Tong Univ, Shanghai 200030, Peoples R China.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0884-0431
EI 1523-4681
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD FEB
PY 2014
VL 29
SU 1
MA MO0180
BP S404
EP S404
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CK9ZS
UT WOS:000356598702331
ER
PT J
AU Maeda, A
Ono, M
Kilts, T
Li, L
Holmbeck, K
Robey, P
Young, M
AF Maeda, Azusa
Ono, Mitsuaki
Kilts, Tina
Li, Li
Holmbeck, Kenn
Robey, Pamela
Young, Marian
TI WISP1/CCN4 controls bone mass by uncoupling osteoblast and osteoclast
function potentially by regulation of Wnt signaling.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research
CY SEP 12-15, 2014
CL Houston, TX
SP Amer Soc Bone & Mineral Res
C1 [Maeda, Azusa; Ono, Mitsuaki; Kilts, Tina; Li, Li; Holmbeck, Kenn; Young, Marian] NIH, Bethesda, MD USA.
[Robey, Pamela] Natl Inst Dent & Craniofacial Res, New York, NY USA.
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 0884-0431
EI 1523-4681
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD FEB
PY 2014
VL 29
SU 1
MA MO0189
BP S408
EP S409
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CK9ZS
UT WOS:000356598702340
ER
PT J
AU Mirigian, L
Makareeva, E
Mertz, E
Perosky, J
Kozloff, K
Leikin, S
AF Mirigian, Lynn
Makareeva, Elena
Mertz, Edward
Perosky, Joseph
Kozloff, Kenneth
Leikin, Sergey
TI Osteoblast malfunction in the G610C model of osteogensis imperfecta
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research
CY SEP 12-15, 2014
CL Houston, TX
SP Amer Soc Bone & Mineral Res
C1 [Mirigian, Lynn; Makareeva, Elena; Mertz, Edward; Leikin, Sergey] NIH, Bethesda, MD USA.
[Perosky, Joseph] Univ Michigan, Ann Arbor, MI 48109 USA.
[Kozloff, Kenneth] Univ Michigan, Dept Orthopaed Surg, Ann Arbor, MI 48109 USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0884-0431
EI 1523-4681
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD FEB
PY 2014
VL 29
SU 1
MA MO0430
BP S483
EP S484
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CK9ZS
UT WOS:000356598702575
ER
PT J
AU Moseley, K
Chia, C
Simonsick, E
Egan, J
Sellmeyer, D
AF Moseley, Kendall
Chia, Chee
Simonsick, Eleanor
Egan, Josephine
Sellmeyer, Deborah
TI Sex-specific differences in the relationship between glycemic status and
hip geometry: The Baltimore Longitudinal Study of Aging.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research
CY SEP 12-15, 2014
CL Houston, TX
SP Amer Soc Bone & Mineral Res
C1 [Moseley, Kendall; Sellmeyer, Deborah] Johns Hopkins Bayview Med Ctr, Div Endocrinol, Baltimore, MD USA.
[Chia, Chee; Simonsick, Eleanor; Egan, Josephine] NIA, Bethesda, MD 20892 USA.
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 0884-0431
EI 1523-4681
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD FEB
PY 2014
VL 29
SU 1
MA SU0409
BP S331
EP S331
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CK9ZS
UT WOS:000356598702096
ER
PT J
AU Ovejero, D
Bhattacharyya, N
Burke, A
Tosi, L
Fisher, L
McCarthy, E
Lim, Y
Choate, K
Collins, M
AF Ovejero, Diana
Bhattacharyya, Nisan
Burke, Andrea
Tosi, Laura
Fisher, Larry
McCarthy, Edward
Lim, Young
Choate, Keith
Collins, Michael
TI Hyperactive RAS Mutations in the Bone have an Intrinsic Negative Effect
on Mineralization in Cutaneous-Skeletal-Hypophosphatemia Syndrome.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research
CY SEP 12-15, 2014
CL Houston, TX
SP Amer Soc Bone & Mineral Res
C1 [Ovejero, Diana; Bhattacharyya, Nisan; Burke, Andrea; Collins, Michael] NIH, Bethesda, MD USA.
[Tosi, Laura] Childrens Natl Med Ctr, Washington, DC USA.
[Fisher, Larry] Natl Inst Dent & Craniofacial Res, New York, NY USA.
[McCarthy, Edward] Johns Hopkins Med Inst, Baltimore, MD USA.
[Lim, Young; Choate, Keith] Yale Univ, Sch Med, New Haven, CT 06520 USA.
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 0884-0431
EI 1523-4681
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD FEB
PY 2014
VL 29
SU 1
MA SA0125
BP S147
EP S147
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CK9ZS
UT WOS:000356598701131
ER
PT J
AU Ramnitz, M
Gourh, P
Del Rivero, J
Ovejero, D
Bhattacharyya, N
Guthrie, L
Goldbach-Mansky, R
Wodajo, F
Ichikawa, S
Imel, E
Econs, M
White, K
Kirmse, B
Boskey, A
Molinolo, A
Gafni, R
Collins, M
AF Ramnitz, Mary
Gourh, Pravitt
Del Rivero, Jaydira
Ovejero, Diana
Bhattacharyya, Nisan
Guthrie, Lori
Goldbach-Mansky, Raphaela
Wodajo, Felasfa
Ichikawa, Shoji
Imel, Erik
Econs, Michael
White, Kenneth
Kirmse, Brian
Boskey, Adele
Molinolo, Alfredo
Gafni, Rachel
Collins, Michael
TI Clinical Characterization of a Cohort of Patients with Familial Tumoral
Calcinosis.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research
CY SEP 12-15, 2014
CL Houston, TX
SP Amer Soc Bone & Mineral Res
C1 [Ramnitz, Mary; Gourh, Pravitt; Del Rivero, Jaydira; Ovejero, Diana; Bhattacharyya, Nisan; Guthrie, Lori; Goldbach-Mansky, Raphaela; Molinolo, Alfredo; Gafni, Rachel; Collins, Michael] NIH, Bethesda, MD USA.
[Wodajo, Felasfa] Virginia Hosp Ctr, Blacksburg, VA USA.
[Ichikawa, Shoji; Imel, Erik; White, Kenneth] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
[Econs, Michael] Indiana Univ, Bloomington, IN 47405 USA.
[Kirmse, Brian] Childrens Natl Med Ctr, Washington, DC USA.
[Boskey, Adele] Hosp Special Surg, New York, NY USA.
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 0884-0431
EI 1523-4681
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD FEB
PY 2014
VL 29
SU 1
MA SA0441
BP S202
EP S202
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CK9ZS
UT WOS:000356598701297
ER
PT J
AU Reich, ADI
Farber, C
Barnes, A
Becerra, P
Rauch, F
Cabral, WA
Bae, A
Glorieux, F
Clemens, T
Marini, J
AF Reich, A. D. I.
Farber, Charles
Barnes, Aileen
Becerra, Patricia
Rauch, Frank
Cabral, Wayne A.
Bae, Alison
Glorieux, Francis
Clemens, Thomas
Marini, Joan
TI Two Distinct Mutations in IFITM5 Causing Different Forms of Osteogenesis
Imperfecta Using Reciprocal Mechanisms
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research
CY SEP 12-15, 2014
CL Houston, TX
SP Amer Soc Bone & Mineral Res
C1 [Reich, A. D. I.] NIH, Bethesda, MD USA.
[Farber, Charles] Univ Virginia, Charlottesville, VA 22903 USA.
[Barnes, Aileen; Cabral, Wayne A.; Bae, Alison] NICHD, NIH, BEMB, Bethesda, MD USA.
[Becerra, Patricia] NEI, NIH, Prot Struct & Funct Sect, Bethesda, MD USA.
[Rauch, Frank; Glorieux, Francis; Clemens, Thomas] Shriners Hosp Children, Montreal, PQ, Canada.
[Glorieux, Francis] McGill Univ, Montreal, PQ H3A 2T5, Canada.
[Clemens, Thomas] Johns Hopkins Univ, Baltimore, MD 21218 USA.
[Marini, Joan] NICHHD, Rockville, MD USA.
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 0884-0431
EI 1523-4681
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD FEB
PY 2014
VL 29
SU 1
MA MO0431
BP S484
EP S484
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CK9ZS
UT WOS:000356598702576
ER
PT J
AU Sahni, S
Tucker, K
Fox, C
Kiel, D
Hannan, M
AF Sahni, Shivani
Tucker, Katherine
Fox, Caroline
Kiel, Douglas
Hannan, Marian
TI Association of serum uric acid concentration with bone: Roles of age and
vitamin C intake
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research
CY SEP 12-15, 2014
CL Houston, TX
SP Amer Soc Bone & Mineral Res
C1 [Sahni, Shivani] Hebrew SeniorLife, Inst Aging Res, Roslindale, MA USA.
[Sahni, Shivani; Hannan, Marian] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Tucker, Katherine] Univ Massachusetts Lowell, Lowell, MA USA.
[Fox, Caroline] Harvard Univ, Sch Med, Framingham Heart Study, NHLBI, Cambridge, MA 02138 USA.
[Kiel, Douglas] Hebrew SeniorLife, Roslindale, MA USA.
[Hannan, Marian] HSL Inst Aging Res, Roslindale, MA USA.
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 0884-0431
EI 1523-4681
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD FEB
PY 2014
VL 29
SU 1
MA MO0327
BP S449
EP S449
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CK9ZS
UT WOS:000356598702474
ER
PT J
AU Samelson, E
Bouxsein, M
Brochin, E
Zhang, XC
Meng, CA
Broe, K
Hogan, M
Carroll, D
McLean, R
Hannan, M
Cupples, LA
Fox, C
Kiel, D
AF Samelson, Elizabeth (Lisa)
Bouxsein, Mary
Brochin, Elana
Zhang, Xiaochun
Meng, Ching-An
Broe, Kerry
Hogan, Mary
Carroll, Danette
McLean, Robert
Hannan, Marian
Cupples, L. Adrienne
Fox, Caroline
Kiel, Douglas
TI Deficits in Cortical Bone Density and Microstructure in Type 2 Diabetes:
Framingham HR-pQCT Study
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research
CY SEP 12-15, 2014
CL Houston, TX
SP Amer Soc Bone & Mineral Res
C1 [Samelson, Elizabeth (Lisa)] Harvard Univ, Sch Med, Hebrew SeniorLife, Cambridge, MA 02138 USA.
[Bouxsein, Mary] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Cambridge, MA 02138 USA.
[Brochin, Elana; Zhang, Xiaochun; Meng, Ching-An; Broe, Kerry; Hogan, Mary; Carroll, Danette; Cupples, L. Adrienne] Hebrew SeniorLife, Inst Aging Res, Roslindale, MA USA.
[Hannan, Marian; Cupples, L. Adrienne] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Hannan, Marian] HSL Inst Aging Res, Boston, MA USA.
[Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, NHLBI Framingham Heart Study, Boston, MA 02215 USA.
[Fox, Caroline] NHLBI, NIH, Bethesda, MD USA.
[Kiel, Douglas] Hebrew SeniorLife, Roslindale, MA USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0884-0431
EI 1523-4681
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD FEB
PY 2014
VL 29
SU 1
MA 1083
BP S28
EP S28
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CK9ZS
UT WOS:000356598700084
ER
PT J
AU Schileo, E
Palmadori, I
Taddei, F
Coran, A
Sigursson, S
Gudnason, V
Harris, T
Foresta, C
AF Schileo, Enrico
Palmadori, Ilaria
Taddei, Fulvia
Coran, Alessandro
Sigursson, Sigurur
Gudnason, Vilmundur
Harris, Tamara
Foresta, Carlo
TI Proximal Femur Strength and Cortical Thickness Estimates in Klinefelter
Syndrome and Post-Menopausal Women
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research
CY SEP 12-15, 2014
CL Houston, TX
SP Amer Soc Bone & Mineral Res
C1 [Schileo, Enrico; Palmadori, Ilaria; Taddei, Fulvia] Ist Ortoped Rizzoli, Bologna, Italy.
[Coran, Alessandro; Foresta, Carlo] Univ Padua, I-35100 Padua, Italy.
[Sigursson, Sigurur] Iceland Heart Assoc, Kopavogur, Iceland.
[Gudnason, Vilmundur] Iceland Heart Assoc, Res Inst, Kopavogur, Iceland.
[Harris, Tamara] NIA, Intramural Res Program, Bethesda, MD 20892 USA.
RI Gudnason, Vilmundur/K-6885-2015
OI Gudnason, Vilmundur/0000-0001-5696-0084
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 0884-0431
EI 1523-4681
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD FEB
PY 2014
VL 29
SU 1
MA MO0415
BP S478
EP S479
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CK9ZS
UT WOS:000356598702561
ER
PT J
AU Shepherd, J
Fan, B
Powers, C
Stranix-Chibanda, L
Fowler, MG
Dimeglio, L
Mukwasi, C
George, K
Siberry, GK
AF Shepherd, John
Fan, Bo
Powers, Cassidy
Stranix-Chibanda, Lynda
Fowler, Mary Glenn
Dimeglio, Linda
Mukwasi, Cynthia
George, Kathy
Siberry, George K.
TI Novel "3-6'' infant DXA scanning and analysis protocols to isolate
movement and other artifacts.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research
CY SEP 12-15, 2014
CL Houston, TX
SP Amer Soc Bone & Mineral Res
C1 [Shepherd, John; Fan, Bo; Powers, Cassidy] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Stranix-Chibanda, Lynda] Univ Zimbabwe, Coll Hlth Sci, Dept Paediat & Child Hlth, Harare, Zimbabwe.
[Fowler, Mary Glenn] Makerere Univ MU Johns Hopkins Univ JHU Res Colla, Kampala, Uganda.
[Dimeglio, Linda] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
[Mukwasi, Cynthia] Univ Zimbabwe, Harare, Zimbabwe.
[George, Kathy] FHI 360, Durham, NC USA.
[Siberry, George K.] NICHD, NIH, Rockville, MD USA.
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 0884-0431
EI 1523-4681
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD FEB
PY 2014
VL 29
SU 1
MA FR0055
BP S59
EP S59
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CK9ZS
UT WOS:000356598700172
ER
PT J
AU Shi, J
Robey, P
Holmbeck, K
AF Shi, Joanne
Robey, Pamela
Holmbeck, Kenn
TI Conditional ablation of MT1-MMP in SM22a-expressing cells identifies
vascular- associated progenitors cells as essential for skeletal
homeostasis.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research
CY SEP 12-15, 2014
CL Houston, TX
SP Amer Soc Bone & Mineral Res
C1 [Shi, Joanne; Robey, Pamela; Holmbeck, Kenn] Natl Inst Dent & Craniofacial Res, Rockville, MD USA.
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 0884-0431
EI 1523-4681
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD FEB
PY 2014
VL 29
SU 1
MA 1142
BP S49
EP S49
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CK9ZS
UT WOS:000356598700143
ER
PT J
AU Varticovski, L
Thompson, B
Baek, S
Shapiro, J
Hager, G
AF Varticovski, Lyuba
Thompson, Bethtrice
Baek, Songjoon
Shapiro, Jay
Hager, Gordon
TI Genome-wide Global Chromatin Landscape during Bone Differentiation from
Normal and Osteogenesis Imperfecta iPS Cells.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research
CY SEP 12-15, 2014
CL Houston, TX
SP Amer Soc Bone & Mineral Res
C1 [Varticovski, Lyuba] NCI, NIH, Bethesda, MD 20892 USA.
[Thompson, Bethtrice] Howard Univ, Washington, DC USA.
[Baek, Songjoon; Hager, Gordon] NCI, LRBGE, NIH, Bethesda, MD 20892 USA.
[Shapiro, Jay] Johns Hopkins, Kennedy Krieger Inst, Baltimore, MD USA.
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 0884-0431
EI 1523-4681
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD FEB
PY 2014
VL 29
SU 1
MA SA0243
BP S168
EP S168
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CK9ZS
UT WOS:000356598701197
ER
PT J
AU Zaidi, M
Sun, L
Yuen, T
Lu, P
Kim, SM
Liu, P
Zhang, KT
Yang, RH
Li, JH
Ji, YT
Chuang, WL
Keutzer, J
Stachnik, A
Mennone, A
Boyer, J
Jain, D
Btady, R
New, M
Liu, J
Mistry, P
AF Zaidi, Mone
Sun, Li
Yuen, Tony
Lu, Ping
Kim, Se-Min
Liu, Peng
Zhang, Kate
Yang, Ruhua
Li, Jianhua
Ji, Yiaoting
Chuang, Wei-Lien
Keutzer, Joan
Stachnik, Agens
Mennone, Albert
Boyer, James
Jain, Dhanpat
Btady, Roscoe
New, Maria
Liu, Jun
Mistry, Pramod
TI Unraveling the Skeletal Pathophysiology in Gaucher Disease and Gba2 as a
Therapeutic Target.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research
CY SEP 12-15, 2014
CL Houston, TX
SP Amer Soc Bone & Mineral Res
C1 [Zaidi, Mone] Mt Sinai Med Ctr, Miami Beach, FL USA.
[Sun, Li; Yuen, Tony; Kim, Se-Min; Ji, Yiaoting] Mt Sinai Sch Med, New York, NY USA.
[Lu, Ping] Bone Program, New York, NY USA.
[Zhang, Kate; Keutzer, Joan; Mennone, Albert] Genzyme, Boston, MA USA.
[Yang, Ruhua; Stachnik, Agens; Boyer, James; Jain, Dhanpat; Liu, Jun; Mistry, Pramod] Yale Univ, Sch Med, New Haven, CT 06520 USA.
[Li, Jianhua] Tount Sinai Sch Med, New York, NY USA.
[Chuang, Wei-Lien] Genzyme Corp, Cambridge, MA USA.
[Btady, Roscoe] NINDS, NIH, Bethesda, MD 20892 USA.
[New, Maria] Mt Sinai Sch Med, Dept Pediat, New York, NY USA.
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 0884-0431
EI 1523-4681
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD FEB
PY 2014
VL 29
SU 1
MA MO0131
BP S390
EP S390
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CK9ZS
UT WOS:000356598702284
ER
PT J
AU Zhu, Y
Aydin, C
Rubera, I
Tauc, M
Chen, M
Weinstein, L
Marshansky, V
Bastepe, M
AF Zhu, Yan
Aydin, Cumhur
Rubera, Isabelle
Tauc, Michel
Chen, Min
Weinstein, Lee
Marshansky, Vladimir
Bastepe, Murat
TI Segment specific role of Gs alpha in mediating parathyroid hormone
actions in the renal proximal tubule.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research
CY SEP 12-15, 2014
CL Houston, TX
SP Amer Soc Bone & Mineral Res
C1 [Zhu, Yan; Bastepe, Murat] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA.
[Aydin, Cumhur] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
[Aydin, Cumhur; Marshansky, Vladimir] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Rubera, Isabelle; Tauc, Michel] Univ Nice Sophia Antipolis, CNRS LP2M 7370, Nice, France.
[Chen, Min; Weinstein, Lee] NIDDK, Bethesda, MD USA.
[Marshansky, Vladimir] Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02114 USA.
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 0884-0431
EI 1523-4681
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD FEB
PY 2014
VL 29
SU 1
MA SU0143
BP S252
EP S253
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CK9ZS
UT WOS:000356598701452
ER
PT J
AU David, M
Malti, O
AlGhatrif, M
Wright, J
Canepa, M
Strait, JB
AF David, Melissa
Malti, Omar
AlGhatrif, Majd
Wright, Jeanette
Canepa, Marco
Strait, James B.
TI Pulse Wave Velocity Testing in the Baltimore Longitudinal Study of Aging
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Article
DE Medicine; Issue 84; Pulse Wave Velocity (PWV); Pulse Wave Analysis
(PWA); Arterial stiffness; Aging; Cardiovascular; Carotid-femoral pulse
ID EXPERT CONSENSUS DOCUMENT; ARTERIAL STIFFNESS; DISEASE
AB Carotid-femoral pulse wave velocity is considered the gold standard for measurements of central arterial stiffness obtained through noninvasive methods(1). Subjects are placed in the supine position and allowed to rest quietly for at least 10 min prior to the start of the exam. The proper cuff size is selected and a blood pressure is obtained using an oscillometric device. Once a resting blood pressure has been obtained, pressure waveforms are acquired from the right femoral and right common carotid arteries. The system then automatically calculates the pulse transit time between these two sites (using the carotid artery as a surrogate for the descending aorta). Body surface measurements are used to determine the distance traveled by the pulse wave between the two sampling sites. This distance is then divided by the pulse transit time resulting in the pulse wave velocity. The measurements are performed in triplicate and the average is used for analysis.
C1 [David, Melissa; Malti, Omar; AlGhatrif, Majd; Wright, Jeanette; Canepa, Marco; Strait, James B.] NIA, Clin Res Branch, Bethesda, MD 20892 USA.
RP Strait, JB (reprint author), NIA, Clin Res Branch, Bethesda, MD 20892 USA.
EM straitj@mail.nih.gov
FU Intramural Research Program of the NIH, National Institute on Aging;
Baltimore Longitudinal Study on Aging; MedStar Research Institute
FX This research was supported by the Intramural Research Program of the
NIH, National Institute on Aging and the Baltimore Longitudinal Study on
Aging. A portion of that support was through an R&D contract with
MedStar Research Institute. Standard protocol and technical expertise
was provided by AtCor.
NR 16
TC 0
Z9 0
U1 0
U2 2
PU JOURNAL OF VISUALIZED EXPERIMENTS
PI CAMBRIDGE
PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA
SN 1940-087X
J9 JOVE-J VIS EXP
JI J. Vis. Exp.
PD FEB
PY 2014
IS 84
AR e50817
DI 10.3791/50817
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CA0JL
UT WOS:000348604100009
PM 24561745
ER
PT J
AU Bach, A
Kriebs, U
Wissenbach, U
Jha, A
Mannebach-Gotz, S
Zimmermann, K
Vogt, D
Scholz, A
Muallem, S
Pfeifer, A
Weissgerber, P
Flockerzi, V
Lipp, P
Tsvilovskyy, V
Freichel, M
AF Bach, Aline
Kriebs, Ulrich
Wissenbach, Ulrich
Jha, Archana
Mannebach-Goetz, Stefanie
Zimmermann, Katrin
Vogt, Dominik
Scholz, Anke
Muallem, Shmuel
Pfeifer, Alexander
Weissgerber, Petra
Flockerzi, Veit
Lipp, Peter
Tsvilovskyy, Volodymyr
Freichel, Marc
TI Topology and subcellular localization of TMEM2, a transmembrane protein
regulating amylase secretion from acinar cells
SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
LA English
DT Meeting Abstract
CT 80th Annual Meeting of the
Deutsche-Gesellschaft-fur-Experimentelle-und-Klinische-Pharmakologie-und
-Toxikologie-e-V
CY APR 01-03, 2014
CL Hannover, GERMANY
SP Deutsch Gesell Experimentelle & Klinische Pharmakologie & Pharmakologie e V
C1 [Bach, Aline; Kriebs, Ulrich; Vogt, Dominik; Tsvilovskyy, Volodymyr; Freichel, Marc] Heidelberg Univ, Inst Pharmakol, D-69115 Heidelberg, Germany.
[Wissenbach, Ulrich; Mannebach-Goetz, Stefanie; Weissgerber, Petra; Flockerzi, Veit] Univ Saarland, Expt & Klin Pharmakol & Toxikol, Homburg, Germany.
[Jha, Archana; Muallem, Shmuel] Natl Inst Dent & Craniofacial Res, NIH, Epithelial Signaling & Transport Sect, Mol Physiol & Therapeut Branch, Bethesda, MD USA.
[Zimmermann, Katrin; Pfeifer, Alexander] Univ Bonn, Inst Pharmakol & Toxikol, Bonn, Germany.
[Scholz, Anke; Lipp, Peter] Univ Saarland, Inst Mol Zellbiol, Homburg, Germany.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0028-1298
EI 1432-1912
J9 N-S ARCH PHARMACOL
JI Naunyn-Schmiedebergs Arch. Pharmacol.
PD FEB
PY 2014
VL 387
SU 1
MA 100
BP S26
EP S26
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CP0AP
UT WOS:000359538500101
ER
PT J
AU Buhler, A
Walliser, C
Haas, J
Kraus, JM
Filingeri, D
Havenith, G
Kestler, HA
Milner, JD
Gierschik, P
AF Buehler, Ania
Walliser, Claudia
Haas, Jennifer
Kraus, Johann M.
Filingeri, Davide
Havenith, George
Kestler, Hans A.
Milner, Joshua D.
Gierschik, Peter
TI Cool-temperature-mediated activation of phospholipase C-gamma 2 in
PLAID, a novel form of human hereditary antibody deficiency and immune
dysregulation
SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
LA English
DT Meeting Abstract
CT 80th Annual Meeting of the
Deutsche-Gesellschaft-fur-Experimentelle-und-Klinische-Pharmakologie-und
-Toxikologie-e-V
CY APR 01-03, 2014
CL Hannover, GERMANY
SP Deutsch Gesell Experimentelle & Klinische Pharmakologie & Pharmakologie e V
C1 [Buehler, Ania; Walliser, Claudia; Haas, Jennifer; Gierschik, Peter] Univ Ulm, Med Ctr, Inst Pharmacol & Toxicol, D-89069 Ulm, Germany.
[Kraus, Johann M.; Kestler, Hans A.] Univ Ulm, Med Syst Biol, D-89069 Ulm, Germany.
[Filingeri, Davide; Havenith, George] Univ Loughborough, Environm Ergon Res Ctr, Loughborough, Leics, England.
[Milner, Joshua D.] NIAID, NIH, Allerg Inflammat Unit, Lab Allerg Dis, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0028-1298
EI 1432-1912
J9 N-S ARCH PHARMACOL
JI Naunyn-Schmiedebergs Arch. Pharmacol.
PD FEB
PY 2014
VL 387
SU 1
MA 013
BP S5
EP S6
PG 2
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CP0AP
UT WOS:000359538500014
ER
PT J
AU Keller, K
Maass, M
Dizayee, S
Muller-Ehmsen, J
Birnbaumer, L
Engelhardt, S
Herzig, S
Matthes, J
AF Keller, Kirsten
Maass, Martina
Dizayee, Sara
Mueller-Ehmsen, Jochen
Birnbaumer, Lutz
Engelhardt, Stefan
Herzig, Stefan
Matthes, Jan
TI Reduction of survival and development of cardiac hypertrophy by G(12)
deficiency in beta(1)-adrenoceptor overexpressing mice
SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
LA English
DT Meeting Abstract
CT 80th Annual Meeting of the
Deutsche-Gesellschaft-fur-Experimentelle-und-Klinische-Pharmakologie-und
-Toxikologie-e-V
CY APR 01-03, 2014
CL Hannover, GERMANY
SP Deutsch Gesell Experimentelle & Klinische Pharmakologie & Pharmakologie e V
C1 [Keller, Kirsten; Dizayee, Sara; Herzig, Stefan; Matthes, Jan] Univ Cologne, Cologne, Germany.
[Maass, Martina; Mueller-Ehmsen, Jochen] Uniklin Koln, Innere Med Klin 3, Cologne, Germany.
[Birnbaumer, Lutz] NIH, Transmembrane Signaling Grp, Durham, NC USA.
[Engelhardt, Stefan] Tech Univ Munich, Inst Pharmakol & Toxikol, D-80290 Munich, Germany.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0028-1298
EI 1432-1912
J9 N-S ARCH PHARMACOL
JI Naunyn-Schmiedebergs Arch. Pharmacol.
PD FEB
PY 2014
VL 387
SU 1
MA 223
BP S56
EP S56
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CP0AP
UT WOS:000359538500224
ER
PT J
AU Leiss, V
Flockerzie, K
Birnbaumer, L
Schurmann, A
Nurnberg, B
AF Leiss, Veronika
Flockerzie, Katarina
Birnbaumer, Lutz
Schuermann, Annette
Nuernberg, Bernd
TI Pancreatic beta-cell G alpha(i2) stimulates insulin secretion
SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
LA English
DT Meeting Abstract
CT 80th Annual Meeting of the
Deutsche-Gesellschaft-fur-Experimentelle-und-Klinische-Pharmakologie-und
-Toxikologie-e-V
CY APR 01-03, 2014
CL Hannover, GERMANY
SP Deutsch Gesell Experimentelle & Klinische Pharmakologie & Pharmakologie e V
C1 [Leiss, Veronika; Flockerzie, Katarina; Nuernberg, Bernd] Inst Pharmakol, Tubingen, Germany.
[Birnbaumer, Lutz] NIEHS, Res Triangle Pk, NC USA.
[Schuermann, Annette] Deutsch Inst Ernahrungsforsch, Nuthetal, Germany.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0028-1298
EI 1432-1912
J9 N-S ARCH PHARMACOL
JI Naunyn-Schmiedebergs Arch. Pharmacol.
PD FEB
PY 2014
VL 387
SU 1
MA 245
BP S61
EP S61
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CP0AP
UT WOS:000359538500246
ER
PT J
AU Littmann, T
Wainer, IW
Ozawa, T
Goettle, M
Seifert, R
AF Littmann, Timo
Wainer, Irving William
Ozawa, Takeaki
Goettle, Martin
Seifert, Roland
TI Differential recruitment of beta-arrestin by stereoisomers of
beta(2)-adrenoceptor agonists
SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
LA English
DT Meeting Abstract
CT 80th Annual Meeting of the
Deutsche-Gesellschaft-fur-Experimentelle-und-Klinische-Pharmakologie-und
-Toxikologie-e-V
CY APR 01-03, 2014
CL Hannover, GERMANY
SP Deutsch Gesell Experimentelle & Klinische Pharmakologie & Pharmakologie e V
ID CELLS
C1 [Littmann, Timo; Goettle, Martin; Seifert, Roland] Hannover Med Sch, Inst Pharmacol, Hannover, Germany.
[Wainer, Irving William] NIA, NIH, Bethesda, MD 20892 USA.
[Ozawa, Takeaki] Univ Tokyo, Dept Chem, Tokyo 1138654, Japan.
NR 3
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0028-1298
EI 1432-1912
J9 N-S ARCH PHARMACOL
JI Naunyn-Schmiedebergs Arch. Pharmacol.
PD FEB
PY 2014
VL 387
SU 1
MA 252
BP S63
EP S63
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CP0AP
UT WOS:000359538500253
ER
PT J
AU Reinartz, MT
Littmann, T
Wainer, IW
Ozawa, T
Dove, S
Seifert, R
AF Reinartz, Michael T.
Littmann, Timo
Wainer, Irving William
Ozawa, Takeaki
Dove, Stefan
Seifert, Roland
TI Quantifying ligand bias of enantiopure fenoterol derivatives in
molecular and cellular beta(2)-adrenergic assay systems
SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
LA English
DT Meeting Abstract
CT 80th Annual Meeting of the
Deutsche-Gesellschaft-fur-Experimentelle-und-Klinische-Pharmakologie-und
-Toxikologie-e-V
CY APR 01-03, 2014
CL Hannover, GERMANY
SP Deutsch Gesell Experimentelle & Klinische Pharmakologie & Pharmakologie e V
C1 [Reinartz, Michael T.; Littmann, Timo; Seifert, Roland] Hannover Med Sch, Inst Pharmacol, Hannover, Germany.
[Wainer, Irving William] NIA, Clin Invest Lab, Baltimore, MD 21224 USA.
[Ozawa, Takeaki] Univ Tokyo, Dept Chem, Tokyo 1138654, Japan.
[Dove, Stefan] Univ Regensburg, Dept Pharmaceut & Med Chem 2, D-93053 Regensburg, Germany.
NR 3
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0028-1298
EI 1432-1912
J9 N-S ARCH PHARMACOL
JI Naunyn-Schmiedebergs Arch. Pharmacol.
PD FEB
PY 2014
VL 387
SU 1
MA 062
BP S17
EP S17
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CP0AP
UT WOS:000359538500063
ER
PT J
AU Tsvilovskyy, V
Geminn, J
Mannebach, S
Kriebs, U
Dietrich, A
Weissgerber, P
Flockerzi, V
Birnbaumer, L
Freichel, M
AF Tsvilovskyy, Volodymyr
Geminn, Julia
Mannebach, Stefanie
Kriebs, Ulrich
Dietrich, Alexander
Weissgerber, Petra
Flockerzi, Veit
Birnbaumer, Lutz
Freichel, Marc
TI Agonist evoked Ca2+ elevation in mast cells depends on TRPC protein
expression
SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
LA English
DT Meeting Abstract
CT 80th Annual Meeting of the
Deutsche-Gesellschaft-fur-Experimentelle-und-Klinische-Pharmakologie-und
-Toxikologie-e-V
CY APR 01-03, 2014
CL Hannover, GERMANY
SP Deutsch Gesell Experimentelle & Klinische Pharmakologie & Pharmakologie e V
C1 [Tsvilovskyy, Volodymyr; Geminn, Julia; Kriebs, Ulrich; Freichel, Marc] Heidelberg Univ, Pharmakol Inst, D-69115 Heidelberg, Germany.
[Mannebach, Stefanie; Weissgerber, Petra; Flockerzi, Veit] Univ Saarland, Expt & Klin Pharmakol & Toxikol, Homburg, Germany.
[Dietrich, Alexander] Univ Munich, Walther Straub Inst Pharmakol & Toxikol, D-81377 Munich, Germany.
[Birnbaumer, Lutz] NIEHS, Neurobiol Lab, Res Triangle Pk, NC USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0028-1298
EI 1432-1912
J9 N-S ARCH PHARMACOL
JI Naunyn-Schmiedebergs Arch. Pharmacol.
PD FEB
PY 2014
VL 387
SU 1
MA 078
BP S21
EP S21
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CP0AP
UT WOS:000359538500079
ER
PT J
AU Sapp, JC
Dong, D
Stark, C
Ivey, LE
Hooker, G
Biesecker, LG
Biesecker, BB
AF Sapp, J. C.
Dong, D.
Stark, C.
Ivey, L. E.
Hooker, G.
Biesecker, L. G.
Biesecker, B. B.
TI Parental attitudes, values, and beliefs toward the return of results
from exome sequencing in children
SO CLINICAL GENETICS
LA English
DT Article
DE genome sequencing; incidental findings; patient preferences; theory of
reasoned action
ID RESEARCH PARTICIPANTS; GENETIC RESEARCH; GENOMICS; RECOMMENDATIONS;
PERSPECTIVES; PREFERENCES; ETHICS; MINORS; POLICY
AB Exome sequencing is being offered for children with undiagnosed conditions to identify a primary (causative) variant. Parental preferences for learning secondary (incidental) variants are largely unexplored. Our objective was to characterize values and beliefs that shape parents' preferences for learning their children's sequencing results. We conducted semi-structured interviews with 25 parents of 13 minor probands with a variety of rare genetic conditions. Parents were asked to discuss their preferences to receive four types of results from exome sequencing. Many parents preferred to receive all types of results. Parents had the most positive attitudes toward learning about variants that predispose to disorders treatable or preventable in childhood. They had reservations about learning about predispositions for untreatable adult-onset conditions and carrier status for recessive conditions. Parents described their success in coping with their child's condition as evidence for an ability to manage any additional negative health information. They felt responsible for learning about secondary variants, desiring a gain in control over their child's health. Our findings suggest that investigators should incorporate parents' perceptions of the value in receiving secondary variant information about their children when designing studies employing exome sequencing.
C1 [Sapp, J. C.; Dong, D.; Ivey, L. E.; Biesecker, L. G.] NHGRI, Genet Dis Res Branch, Bethesda, MD 20892 USA.
[Stark, C.; Hooker, G.; Biesecker, B. B.] NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA.
RP Sapp, JC (reprint author), NHGRI, CGC, 10 Ctr Dr,Bldg 10,Room 3C710, Bethesda, MD 20892 USA.
EM sappj@mail.nih.gov
FU National Human Genome Research Institute
FX The authors thank the participants in this study for their time and
participation. We thank Danielle Brinckman for coordinating the
interviews, Barbara Hamlington for conducting one of them, and Tyler
Fisher and Molly Crenshaw for their editorial assistance. The Intramural
Research Program of the National Human Genome Research Institute funded
this research.
NR 24
TC 27
Z9 27
U1 1
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9163
EI 1399-0004
J9 CLIN GENET
JI Clin. Genet.
PD FEB
PY 2014
VL 85
IS 2
BP 120
EP 126
DI 10.1111/cge.12254
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 287AZ
UT WOS:000329511700004
PM 24033230
ER
PT J
AU Canepa, M
AlGhatrif, M
Strait, JB
Cheng, HM
Chuang, SY
Chen, CH
Brunelli, C
Ferrucci, L
Lakatta, EG
AF Canepa, M.
AlGhatrif, M.
Strait, J. B.
Cheng, H-M
Chuang, S-Y
Chen, C-H
Brunelli, C.
Ferrucci, L.
Lakatta, E. G.
TI Early contribution of arterial wave reflection to left ventricular
relaxation abnormalities in a community-dwelling population of
normotensive and untreated hypertensive men and women
SO JOURNAL OF HUMAN HYPERTENSION
LA English
DT Article
DE wave reflection; arterial stiffness; augmentation index; pulse wave
velocity; diastolic function; blood pressure
ID DIASTOLIC FUNCTION; HEART-FAILURE; SEX-DIFFERENCES; BLOOD-PRESSURE;
INCIDENT HYPERTENSION; CLINICAL-APPLICATIONS; EJECTION FRACTION;
SYSTOLIC PRESSURE; LOADING SEQUENCE; STIFFNESS
AB We examined the contribution of arterial wave reflection to early abnormalities in left ventricular relaxation, whether this association was modified by gender or hypertension and the role of reflected wave timing and amplitude. We studied a cohort of normotensive and untreated essential hypertensive Taiwanese participants (675 men, 601 women, mean age 52 years). Doppler flow and applanation tonometry were performed to assess carotid-femoral pulse wave velocity (PWV) and augmentation index (AI). Diastolic parameters including the ratio between the peak velocity of early and late diastolic mitral inflow (E/A), E-deceleration time and left atrial (LA) diameter were measured by echocardiography. In multivariate models predicting E/A, women were more likely to have lower E/A than men (beta = -0.08, P<0.001). Al was significantly associated with lower E/A in both men (beta = -0.09, P = 0.005) and women (beta = -0.12, P<0.001) independent of PWV. Inclusion of Al in the overall model reduced the gender difference in E/A by 61% and rendered it nonsignificant. There was a significant interaction between AI and hypertension (P = 0.02). The inverse association between AI and E/A was significant only in normotensive men and women, and only for the amplitude but not timing of the reflected wave. In conclusion, the contribution of wave reflection to left ventricular diastolic dysfunction was independent of arterial stiffness, more pronounced in normotensive individuals and explained a significant portion of the gender difference in diastolic function.
C1 [Canepa, M.; AlGhatrif, M.; Strait, J. B.; Lakatta, E. G.] NIA, Lab Cardiovasc Sci, Human Cardiovasc Studies Unit, NIH, Baltimore, MD 21225 USA.
[Canepa, M.; Strait, J. B.; Ferrucci, L.] NIA, Longitudinal Studies Sect, Translat Gerontol Branch, NIH, Baltimore, MD 21225 USA.
[Canepa, M.; Brunelli, C.] Univ Genoa, Div Cardiol, Res Ctr Cardiovasc Biol, Genoa, Italy.
[AlGhatrif, M.] Johns Hopkins Sch Med, Johns Hopkins Bayview Med Ctr, Dept Med, Baltimore, MD USA.
[Cheng, H-M; Chen, C-H] Taipei Vet Gen Hosp, Dept Med Res & Educ, Taipei, Taiwan.
[Cheng, H-M; Chen, C-H] Natl Yang Ming Univ, Dept Med, Taipei 112, Taiwan.
[Chuang, S-Y] Natl Hlth Res Inst, Res Inst Populat Hlth Sci, Div Prevent Med & Hlth Serv, Miaoli, Taiwan.
RP Canepa, M (reprint author), NIA, Longitudinal Studies Sect, Translat Gerontol Branch, NIH,Harbor Hosp Ctr, Room NM524,3001 S Hanover St, Baltimore, MD 21225 USA.
EM drcanepamarco@gmail.com
RI Chuang, Shao-Yuan/B-3478-2011
FU Intramural Research Program of the NIH, National Institute on Aging, a
grant from the National Science Council [NSC 99-2314-B-010 - 034 -MY3];
Taipei Veterans General Hospital, Taiwan, Republic of China [V99C1-091]
FX This research was supported by the Intramural Research Program of the
NIH, National Institute on Aging, a grant from the National Science
Council (NSC 99-2314-B-010 - 034 -MY3) and an intramural grant
(V99C1-091) from Taipei Veterans General Hospital, Taiwan, Republic of
China.
NR 36
TC 11
Z9 11
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9240
EI 1476-5527
J9 J HUM HYPERTENS
JI J. Hum. Hypertens.
PD FEB
PY 2014
VL 28
IS 2
BP 85
EP 91
DI 10.1038/jhh.2013.86
PG 7
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 286CE
UT WOS:000329441300004
PM 24048294
ER
PT J
AU Bures, R
Clark, R
King, R
Newcomer, S
AF Bures, Regina
Clark, Rebecca
King, Rosalind
Newcomer, Susan
TI Funding Strategies for Population Researchers: Perspectives from the
National Institutes of Health
SO POPULATION RESEARCH AND POLICY REVIEW
LA English
DT Article
DE National Institutes of Health; Eunice Kennedy Shriver National Institute
of Child Health & Human Development; Funding; Population science
AB The purpose of this article is to briefly describe the application and funding process at the National Institutes of Health (NIH). We target our discussion to demographic and population science at the Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD), but the general strategies are applicable to social and behavioral scientists for all NIH funding opportunities.
C1 [Bures, Regina; Clark, Rebecca; King, Rosalind; Newcomer, Susan] NICHD, PDB, Bethesda, MD 20892 USA.
RP Bures, R (reprint author), NICHD, PDB, 6100 Execut Blvd, Bethesda, MD 20892 USA.
EM regina.bures@nih.gov
NR 3
TC 0
Z9 0
U1 0
U2 3
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0167-5923
EI 1573-7829
J9 POPUL RES POLICY REV
JI Popul. Res. Policy Rev.
PD FEB
PY 2014
VL 33
IS 1
BP 1
EP 11
DI 10.1007/s11113-013-9306-5
PG 11
WC Demography
SC Demography
GA 285DO
UT WOS:000329373600001
ER
PT J
AU Wiener, L
Baird, K
Crum, C
Powers, K
Carpenter, P
Baker, KS
MacMillan, ML
Nemecek, E
Lai, JS
Mitchell, SA
Jacobsohn, DA
AF Wiener, Lori
Baird, Kristin
Crum, Caroline
Powers, Kimberly
Carpenter, Paul
Baker, K. Scott
MacMillan, Margaret L.
Nemecek, Eneida
Lai, Jin-Shei
Mitchell, Sandra A.
Jacobsohn, David A.
TI Child and parent perspectives of the chronic graft-versus-host disease
(cGVHD) symptom experience: a concept elicitation study
SO SUPPORTIVE CARE IN CANCER
LA English
DT Article
DE Chronic graft-versus-host disease; Stemcell transplant; Pediatric;
Symptom scale; Patient-reported outcomes (PROs); Qualitative
ID QUALITY-OF-LIFE; CONSENSUS DEVELOPMENT PROJECT; WORKING GROUP-REPORT;
CLINICAL-TRIALS; RISK-FACTORS; TASK-FORCE; VALIDITY; RELIABILITY;
INSTRUMENT; CRITERIA
AB Chronic graft-versus-host disease (cGVHD) is a significant cause of mortality and morbidity after allogeneic hematopoietic cell transplant and is associated with a wide range of distressing symptoms. A pediatric measure of cGVHD-related symptoms is needed to advance clinical research. Our aim was to elicit descriptions of the cGVHD symptom experience directly from children and to compare the specific language used by children to describe their symptoms and the comprehension of symptom concepts across the developmental spectrum.
We used qualitative methods to identify the phrases, terms, and constructs that children (ages 5-8 [n = 8], 9-12 [n = 8], and 13-17 [n = 8]) with cGVHD employ when describing their symptoms. The symptom experience of each participant was determined through individual interviews with each participant and parent (5-7 year olds were interviewed together with a parent). Medical practitioners with experience in evaluating cGVHD performed clinical assessments of each participant.
Pediatric transplant survivors and their parents identified a wide range of bothersome cGVHD symptoms, and common concepts and terminologies to describe these experiences emerged. Overall concordance between patient and parent reports was moderate (70-75 %). No consistent pattern of child under- or over-reporting in comparison to the parent report was observed.
These study results identify concepts and vocabulary to inform item generation for a new pediatric self-report measure of cGVHD symptoms for use in clinical research. The findings also confirm the prevalence and nature of symptom distress in pediatric patients with cGVHD and support implementation of systematic approaches to symptom assessment and intervention in routine clinical practice.
C1 [Wiener, Lori; Baird, Kristin; Crum, Caroline] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Powers, Kimberly] Lurie Childrens Hosp Chicago, Chicago, IL USA.
[Carpenter, Paul; Baker, K. Scott] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA.
[Carpenter, Paul; Baker, K. Scott] Seattle Childrens Hosp, Seattle, WA USA.
[MacMillan, Margaret L.] Univ Minnesota, Sch Med, Blood & Marrow Transplant Program, Minneapolis, MN 55455 USA.
[MacMillan, Margaret L.] Univ Minnesota, Sch Med, Dept Pediat, Amplatz Childrens Hosp, Minneapolis, MN 55455 USA.
[Nemecek, Eneida] Oregon Hlth & Sci Univ, Doernbecher Childrens Hosp, Portland, OR 97201 USA.
[Lai, Jin-Shei] Northwestern Univ, Dept Med Social Sci & Pediat, Chicago, IL 60611 USA.
[Mitchell, Sandra A.] NCI, Outcomes Res Branch, NIH, Bethesda, MD 20892 USA.
[Jacobsohn, David A.] Childrens Natl Med Ctr, Washington, DC 20010 USA.
RP Wiener, L (reprint author), NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM wienerl@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 29
TC 3
Z9 3
U1 3
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0941-4355
EI 1433-7339
J9 SUPPORT CARE CANCER
JI Support. Care Cancer
PD FEB
PY 2014
VL 22
IS 2
BP 295
EP 305
DI 10.1007/s00520-013-1957-6
PG 11
WC Oncology; Health Care Sciences & Services; Rehabilitation
SC Oncology; Health Care Sciences & Services; Rehabilitation
GA 285DH
UT WOS:000329372900004
PM 24077685
ER
PT J
AU Hernandez-Andrade, E
Ahn, H
Szalai, G
Korzeniewski, SJ
Wang, B
King, M
Chaiworapongsa, T
Than, NG
Romero, R
AF Hernandez-Andrade, Edgar
Ahn, Hyunyoung
Szalai, Gabor
Korzeniewski, Steven J.
Wang, Bing
King, Mary
Chaiworapongsa, Tinnakorn
Than, Nandor Gabor
Romero, Roberto
TI EVALUATION OF UTERO-PLACENTAL AND FETAL HEMODYNAMIC PARAMETERS
THROUGHOUT GESTATION IN PREGNANT MICE USING HIGH-FREQUENCY ULTRASOUND
SO ULTRASOUND IN MEDICINE AND BIOLOGY
LA English
DT Article
DE Doppler; Experimental mouse model; Pregnancy; Ductus venosus; Resistance
index
ID UMBILICAL BLOOD-FLOW; MOUSE EMBRYO; GROWTH RESTRICTION; CARDIAC-OUTPUT;
CORD OCCLUSION; WAVE-FORM; DOPPLER; MODEL; FETUS; SHEEP
AB Throughout gestation, changes in maternal and fetal Doppler parameters in pregnant mice, similar to those obtained in human fetuses, were detected using high-frequency ultrasound with a 55-MHz linear probe. In the uterine arteries (UtA), fetal umbilical artery (UA) and fetal ductus venosus (DV) peak systolic velocity increased (UtA, p = 0.04; UA, p = 0.0004; DV, p = 0.02), end-diastolic velocity increased (UtA, p < 0.001; UA, p < 0.0001; DV, p = 0.01) and resistance index decreased (UtA, p = 0.0004; UA, p = 0.0001; DV, p = 0.04) toward the end of pregnancy. In the middle cerebral and carotid arteries, end diastolic velocity increased (p = 0.02 and p < 0.0001) and resistance index decreased (both vessels, p < 0.0001). There was a reduction in the pulsatile pattern in the umbilical vein (p < 0.05). The increased velocities and reduced resistance index suggest a progressive increment in blood flow to the fetal mouse toward the end of pregnancy. Fetal and utero-placental vascular parameters in CD-1 mice can be reliably evaluated using high-frequency ultrasound. (E-mail: romeror@mail.nih.gov) (C) 2014 Published by Elsevier Inc. on behalf ofWorld Federation for Ultrasound in Medicine & Biology.
C1 [Hernandez-Andrade, Edgar; Ahn, Hyunyoung; Szalai, Gabor; Korzeniewski, Steven J.; Wang, Bing; King, Mary; Chaiworapongsa, Tinnakorn; Than, Nandor Gabor; Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
[Hernandez-Andrade, Edgar; Ahn, Hyunyoung; Szalai, Gabor; Korzeniewski, Steven J.; Wang, Bing; King, Mary; Chaiworapongsa, Tinnakorn; Than, Nandor Gabor; Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Detroit, MI USA.
[Hernandez-Andrade, Edgar; Ahn, Hyunyoung; Korzeniewski, Steven J.; King, Mary; Chaiworapongsa, Tinnakorn; Than, Nandor Gabor] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Romero, Roberto] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA.
[Romero, Roberto] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA.
RP Romero, R (reprint author), Hutzel Womens Hosp, Perinatol Res Branch, 3990 John R,Box 4, Detroit, MI 48201 USA.
EM romeror@mail.nih.gov
FU Perinatology Research Branch, Division of Intramural Research, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, Department of Health and
Human Services (NICHD/NIH); NICHD/NIH [HHSN275201300006C]
FX This research was supported, in part, by the Perinatology Research
Branch, Division of Intramural Research, Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health, Department of Health and Human Services (NICHD/NIH) and, in
part, with federal funds from NICHD/NIH under Contract
HHSN275201300006C.-The authors are grateful to Lisa Brossia, Laura
McIntyre and all personnel at the Division of Laboratory Animal
Resources of Wayne State University who provided veterinary care and
husbandry for the animals used in this study. We are grateful to Maureen
McGerty and Andrea Bernard (Wayne State University) for editorial
support. The authors dedicate this work to the memory of our colleague
Mary King, who was part of our team for more than a decade.
NR 53
TC 6
Z9 6
U1 1
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0301-5629
EI 1879-291X
J9 ULTRASOUND MED BIOL
JI Ultrasound Med. Biol.
PD FEB
PY 2014
VL 40
IS 2
BP 351
EP 360
DI 10.1016/j.ultrasmedbio.2013.09.026
PG 10
WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging
SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging
GA 283CF
UT WOS:000329221600010
PM 24342911
ER
PT J
AU Sitzmann, BD
Brown, DI
Garyfallou, VT
Kohama, SG
Mattison, JA
Ingram, DK
Roth, GS
Ottinger, MA
Urbanski, HF
AF Sitzmann, Brandon D.
Brown, Donald I.
Garyfallou, Vasilios T.
Kohama, Steven G.
Mattison, Julie A.
Ingram, Donald K.
Roth, George S.
Ottinger, Mary Ann
Urbanski, Henryk F.
TI Impact of moderate calorie restriction on testicular morphology and
endocrine function in adult rhesus macaques (Macaca mulatta)
SO AGE
LA English
DT Article
DE Calorie restriction; Gene expression; Locomotor activity; Seminiferous
tubules; Testis; Testosterone
ID LUTEINIZING-HORMONE SECRETION; AGE-RELATED DECLINE; TESTOSTERONE
PRODUCTION; SERUM TESTOSTERONE; NONHUMAN-PRIMATES; SEMEN QUALITY;
DIETARY RESTRICTION; CIRCADIAN VARIATION; FOOD RESTRICTION; STRESS
SIGNALS
AB We previously reported that moderate calorie restriction (CR) has minimal impact on testicular gene expression in young adult rhesus macaques, and no obvious negative impact on semen quality or plasma testosterone levels. We now extend these findings by examining the influence of CR on various aspects of the reproductive axis of older males, including 24-h circulating testosterone levels, testicular gene expression, and testicular morphology. Young adult and old adult male rhesus macaques were subjected to either 30 % CR for 5-7 years, or were fed a standard control diet. Analysis of the 24-h plasma testosterone profiles revealed a significant age-associated decline, but no evidence for CR-induced suppression in either the young or old males. Similarly, expression profiling of key genes associated with testosterone biosynthesis and Leydig cell maintenance showed no significant CR-induced changes in either the young or old animals. The only evidence for CR-associated negative effects on the testis was detected in the old animals at the histological level; when old CR animals were compared with their age-matched controls, there was a modest decrease in seminiferous tubule diameter and epithelium height, with a concomitant increase in the number of depleted germ cell lines. Reassuringly, data from this study and our previous study suggest that moderate CR does not negatively impact 24-h plasma testosterone profiles or testicular gene expression. Although there appear to be some minor CR-induced effects on testicular morphology in old animals, it is unclear if these would significantly compromise fertility.
C1 [Sitzmann, Brandon D.; Brown, Donald I.; Garyfallou, Vasilios T.; Kohama, Steven G.; Urbanski, Henryk F.] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Div Neurosci, Beaverton, OR 97006 USA.
[Sitzmann, Brandon D.; Ottinger, Mary Ann] Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA.
[Brown, Donald I.] Univ Valparaiso, Fac Ciencias, Dept Biol & Ciencias Ambientales, Valparaiso, Chile.
[Mattison, Julie A.; Ingram, Donald K.] NIA, NIH, Translat Gerontol Branch, Baltimore, MD 21224 USA.
[Ingram, Donald K.] Louisiana State Univ Syst, Pennington Biomed Res Ctr, Nutr Neurosci & Aging Lab, Baton Rouge, LA 70808 USA.
[Roth, George S.] GeroScience Inc, Pylesville, MD 21132 USA.
[Urbanski, Henryk F.] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Dept Reprod & Dev Sci, Beaverton, OR 97006 USA.
[Urbanski, Henryk F.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA.
[Urbanski, Henryk F.] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA.
[Urbanski, Henryk F.] ONPRC, Div Neurosci, Beaverton, OR 97006 USA.
RP Urbanski, HF (reprint author), ONPRC, Div Neurosci, 505 NW 185th Ave, Beaverton, OR 97006 USA.
EM urbanski@ohsu.edu
FU National Institutes of Health (NIH) [AG-019914, AG-036670, OD-011092];
Intramural Research Program of the NIH; Department of Animal and Avian
Sciences at the University of Maryland
FX This work was supported by National Institutes of Health (NIH) grants
AG-019914, AG-036670, and OD-011092. Additional support was provided by
the Intramural Research Program of the NIH, and the Department of Animal
and Avian Sciences at the University of Maryland. The authors would like
to thank the members of the Oregon National Primate Research Center for
their technical help: Drs. Dario Lemos, Jodi Downs, Yibing Jia, Betsy
Ferguson, Eliot Spindel, and the animal care staff, including the late
Dr. John Fanton. Statistical support graciously provided by Erin Hoerl
Leone at the Florida Fish and Wildlife Research Institute.
NR 72
TC 0
Z9 2
U1 0
U2 6
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0161-9152
EI 1574-4647
J9 AGE
JI Age
PD FEB
PY 2014
VL 36
IS 1
BP 183
EP 197
DI 10.1007/s11357-013-9563-6
PG 15
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 283EE
UT WOS:000329227500015
PM 23881606
ER
PT J
AU Tanner, AE
Philbin, MM
Duval, A
Ellen, J
Kapogiannis, B
Fortenberry, JD
AF Tanner, Amanda E.
Philbin, Morgan M.
Duval, Anna
Ellen, Jonathan
Kapogiannis, Bill
Fortenberry, J. Dennis
CA Adolescent Trials Network HIV AIDS
TI "Youth friendly" clinics: Considerations for linking and engaging
HIV-infected adolescents into care
SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV
LA English
DT Article
DE adolescents; HIV care; youth friendly; clinics; qualitative research
ID RETENTION; BEHAVIORS; SPACE; UNITS
AB Linkage and engagement in care are critical corollaries to the health of HIV-infected adolescents. The adolescent HIV epidemic and adolescents' unique barriers to care necessitates innovation in the provision of care, including the consideration of the clinical experience. Little research has addressed how youth friendly clinics may influence care retention for HIV-infected youth. We conducted 124 interviews with providers, outreach workers, and case managers, at 15 Adolescent Medicine Trials Network clinics. Photographs of each clinic documented the characteristics of the physical space. Constant comparison and content and visual narrative methods were utilized for data analysis. Three elements of youth friendliness were identified for clinics serving HIV-infected youth, including: (1) role of target population (e.g., pediatric, adolescent, HIV); (2) clinics' physical environment; and (3) clinics' social environment. Working to create youth friendly' clinics through changes in physical (e.g., space, entertainment, and educational materials) and social (e.g., staff training related to development, gender, sexual orientation) environments may help reduce HIV-infected adolescents' unique barriers to care engagement. The integration of clinic design and staff training within the organization of a clinical program is helpful in meeting the specialized needs of HIV-infected youth.
C1 [Tanner, Amanda E.] Univ N Carolina, Dept Publ Hlth Educ, Greensboro, NC 27412 USA.
[Philbin, Morgan M.] Johns Hopkins Sch Publ Hlth, Dept Hlth Behav & Soc, Baltimore, MD USA.
[Duval, Anna; Ellen, Jonathan] Johns Hopkins Sch Med, Dept Pediat, Baltimore, MD USA.
[Kapogiannis, Bill] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal & Pediat Infect Dis Branch, Silver Spring, MD USA.
[Fortenberry, J. Dennis] Indiana Univ Sch Med, Dept Pediat, Indianapolis, IN 46202 USA.
RP Tanner, AE (reprint author), Univ N Carolina, Dept Publ Hlth Educ, Greensboro, NC 27412 USA.
EM aetanner@uncg.edu
FU NICHD NIH HHS [U01 HD040474, 3U01 HD040533-09S1, U01 HD040533]; NIMH NIH
HHS [T32 MH019139, P30 MH043520]
NR 26
TC 20
Z9 20
U1 2
U2 12
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND
SN 0954-0121
EI 1360-0451
J9 AIDS CARE
JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv
PD FEB 1
PY 2014
VL 26
IS 2
BP 199
EP 205
DI 10.1080/09540121.2013.808800
PG 7
WC Health Policy & Services; Public, Environmental & Occupational Health;
Psychology, Multidisciplinary; Respiratory System; Social Sciences,
Biomedical
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Psychology; Respiratory System; Biomedical Social Sciences
GA 277IF
UT WOS:000328811500009
PM 23782040
ER
PT J
AU Carter, MC
Metcalfe, DD
Komarow, HD
AF Carter, Melody C.
Metcalfe, Dean D.
Komarow, Hirsh D.
TI Mastocytosis
SO IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA
LA English
DT Article
DE Mast cell; Mastocytosis; KIT; Bone marrow; Skin; Urticaria
ID ACUTE MYELOID-LEUKEMIA; MAST-CELL DISORDERS; SYSTEMIC MASTOCYTOSIS;
URTICARIA PIGMENTOSA; CUTANEOUS MASTOCYTOSIS; INTERFERON-ALPHA; SERUM
TRYPTASE; IMATINIB MESYLATE; KIT MUTATION; BASE-LINE
AB Mastocytosis is a disorder of abnormal mast cell proliferation, with clinical features that include flushing, pruritus, abdominal pain, diarrhea, hypotension, syncope, and musculoskeletal pain. These features are the result of mast cell mediator release and infiltration into target organs. Patients of all ages may be affected, although in children, manifestations primarily involve the skin. Most patients with systemic disease have a somatically acquired activating mutation in the KIT oncogene. This article discusses the causes and pathogenesis of mastocytosis, with an overview of the clinical features and the approach to diagnosis, evaluation, and therapy in adults and pediatric patients.
C1 [Carter, Melody C.; Metcalfe, Dean D.; Komarow, Hirsh D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
RP Komarow, HD (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 1C129A1,10 Ctr Dr, Bethesda, MD 20892 USA.
EM komarowh@niaid.nih.gov
FU Division of Intramural Research, National Institute of Allergy and
Infectious Disease, NIH
FX This work was supported by the Division of Intramural Research, National
Institute of Allergy and Infectious Disease, NIH.
NR 78
TC 11
Z9 11
U1 0
U2 1
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0889-8561
EI 1557-8607
J9 IMMUNOL ALLERGY CLIN
JI Immunol. Allerg. Clin. North Am.
PD FEB
PY 2014
VL 34
IS 1
BP 181
EP +
DI 10.1016/j.iac.2013.09.001
PG 17
WC Allergy; Immunology
SC Allergy; Immunology
GA 281FU
UT WOS:000329086200016
PM 24262698
ER
PT J
AU Arca, B
Struchiner, CJ
Pham, VM
Sferra, G
Lombardo, F
Pombi, M
Ribeiro, JMC
AF Arca, B.
Struchiner, C. J.
Pham, V. M.
Sferra, G.
Lombardo, F.
Pombi, M.
Ribeiro, J. M. C.
TI Positive selection drives accelerated evolution of mosquito salivary
genes associated with blood-feeding
SO INSECT MOLECULAR BIOLOGY
LA English
DT Article
DE evolution; haematophagy; salivary glands
ID ADULT FEMALE MOSQUITO; ANOPHELES-GAMBIAE; MOLECULAR EVOLUTION;
PHYLOGENETIC ANALYSIS; MAXIMUM-LIKELIHOOD; ADAPTIVE EVOLUTION;
NATURAL-SELECTION; MALARIA VECTOR; NEUTRAL THEORY; IMMUNE-SYSTEM
AB The saliva of bloodsucking animals contains dozens to hundreds of proteins that counteract their hosts' haemostasis, inflammation and immunity. It was previously observed that salivary proteins involved in haematophagy are much more divergent in their primary sequence than those of housekeeping function, when comparisons were made between closely related organisms. While this pattern of evolution could result from relaxed selection or drift, it could alternatively be the result of positive selection driven by the intense pressure of the host immune system. We investigated the polymorphism of five different genes associated with blood-feeding in the mosquito Anopheles gambiae and obtained evidence in four genes for sites with signatures of positive selection. These results add salivary gland genes from bloodsucking arthropods to the small list of genes driven by positive selection.
C1 [Arca, B.; Sferra, G.; Lombardo, F.; Pombi, M.] Univ Roma La Sapienza, Dept Publ Hlth & Infect Dis, Parasitol Sect, I-00185 Rome, Italy.
[Struchiner, C. J.] Fundacao Oswaldo Cruz, Escola Nacl Saude Publ, Rio De Janeiro, Brazil.
[Pham, V. M.; Ribeiro, J. M. C.] NIAID, Lab Malaria & Vector Res, Rockville, MD 20852 USA.
RP Ribeiro, JMC (reprint author), NIAID, Lab Malaria & Vector Res, 12735 Twinbrook Pkwy Room 2E32D, Rockville, MD 20852 USA.
EM jribeiro@niaid.nih.gov
RI Lombardo, Fabrizio/J-8511-2014; Ribeiro, Jose/J-7011-2015;
OI Lombardo, Fabrizio/0000-0002-8563-0612; Pombi,
Marco/0000-0002-4382-9922; Arca, Bruno/0000-0002-4029-0984; Ribeiro,
Jose/0000-0002-9107-0818
FU INFRAVEC project [228421]; EVIMalaR NoE [242095]; CNPq; FAPERJ; Division
of Intramural Research, National Institute of Allergy and Infectious
Diseases, National Institutes of Health, USA
FX We thank C. Rizzo (Sapienza University) and R. Dabire (IRSS/Centre
Muraz, Bobo-Dioulasso, Burkina Faso) for help with mosquito collection
and B. R. Marshall (NIAID) for manuscript editing. This work was
supported by funds from the INFRAVEC project (228421) to B. A and partly
by the EVIMalaR NoE (242095). C.J.S. was funded by CNPq and FAPERJ.
J.M.C.R and V. M. P were supported by the Division of Intramural
Research, National Institute of Allergy and Infectious Diseases,
National Institutes of Health, USA.
NR 52
TC 10
Z9 11
U1 2
U2 15
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0962-1075
EI 1365-2583
J9 INSECT MOL BIOL
JI Insect Mol. Biol.
PD FEB
PY 2014
VL 23
IS 1
BP 122
EP 131
DI 10.1111/imb.12068
PG 10
WC Biochemistry & Molecular Biology; Entomology
SC Biochemistry & Molecular Biology; Entomology
GA 282JC
UT WOS:000329166100010
PM 24237399
ER
PT J
AU Chow, HM
Mar, RA
Xu, YS
Liu, SY
Wagage, S
Braun, AR
AF Chow, Ho Ming
Mar, Raymond A.
Xu, Yisheng
Liu, Siyuan
Wagage, Suraji
Braun, Allen R.
TI Embodied Comprehension of Stories: Interactions between Language Regions
and Modality-specific Neural Systems
SO JOURNAL OF COGNITIVE NEUROSCIENCE
LA English
DT Article
ID ANTERIOR TEMPORAL-LOBES; SEMANTIC MEMORY; TEXT COMPREHENSION; SOCIAL
COGNITION; HUMAN AMYGDALA; NARRATIVE COMPREHENSION; PREFRONTAL CORTEX;
FMRI DATA; BRAIN; MOTOR
AB The embodied view of language processing proposes that comprehension involves multimodal simulations, a process that retrieves a comprehender's perceptual, motor, and affective knowledge through reactivation of the neural systems responsible for perception, action, and emotion. Although evidence in support of this idea is growing, the contemporary neuroanatomical model of language suggests that comprehension largely emerges as a result of interactions between frontotemporal language areas in the left hemisphere. If modality-specific neural systems are involved in comprehension, they are not likely to operate in isolation but should interact with the brain regions critical to language processing. However, little is known about the ways in which language and modality-specific neural systems interact. To investigate this issue, we conducted a functional MRI study in which participants listened to stories that contained visually vivid, action-based, and emotionally charged content. Activity of neural systems associated with visual-spatial, motor, and affective processing were selectively modulated by the relevant story content. Importantly, when functional connectivity patterns associated with the left inferior frontal gyrus (LIFG), the left posterior middle temporal gyrus (pMTG), and the bilateral anterior temporal lobes (aTL) were compared, both LIFG and pMTG, but not the aTL, showed enhanced connectivity with the three modality-specific systems relevant to the story content. Taken together, our results suggest that language regions are engaged in perceptual, motor, and affective simulations of the described situation, which manifest through their interactions with modality-specific systems. On the basis of our results and past research, we propose that the LIFG and pMTG play unique roles in multimodal simulations during story comprehension.
C1 [Chow, Ho Ming; Xu, Yisheng; Liu, Siyuan; Wagage, Suraji; Braun, Allen R.] NIH, Bethesda, MD 20892 USA.
[Mar, Raymond A.] York Univ, Toronto, ON M3J 2R7, Canada.
RP Chow, HM (reprint author), NIH, 10-5C410,10 Ctr Dr, Bethesda, MD 20892 USA.
EM chowh@nidcd.nih.gov
FU NIDCD
FX The authors would like to thank Maja Djikic for her assistance in story
composition. We also thank Alex Martin for helpful discussions and the
NIH Fellows Editorial Board for editing an earlier version of this
paper. This work was supported by the Intramural Research Program of the
NIDCD.
NR 71
TC 11
Z9 11
U1 0
U2 28
PU MIT PRESS
PI CAMBRIDGE
PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA
SN 0898-929X
EI 1530-8898
J9 J COGNITIVE NEUROSCI
JI J. Cogn. Neurosci.
PD FEB
PY 2014
VL 26
IS 2
BP 279
EP 295
DI 10.1162/jocn_a_00487
PG 17
WC Neurosciences; Psychology, Experimental
SC Neurosciences & Neurology; Psychology
GA 282HU
UT WOS:000329162600006
PM 24047383
ER
PT J
AU Ma, N
He, YD
Xiao, H
Han, GC
Chen, GJ
Wang, Y
Wang, K
Hou, CM
Yang, XM
Marrero, B
Wang, YJ
Shen, BF
Li, Y
Wang, RX
AF Ma, Ning
He, Youdi
Xiao, He
Han, Gencheng
Chen, Guojiang
Wang, Yi
Wang, Ke
Hou, Chunmei
Yang, Xiaomei
Marrero, Bernadette
Wang, Yujuan
Shen, Beifen
Li, Yan
Wang, Renxi
TI BAFF maintains T-cell survival by inducing OPN expression in B cells
SO MOLECULAR IMMUNOLOGY
LA English
DT Article
DE T cells; BAFF; EAE; OPN
ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MULTIPLE-SCLEROSIS;
THERAPEUTIC TARGETS; NERVOUS-SYSTEM; OSTEOPONTIN; CYTOKINE; DISEASE;
MICE; HOMEOSTASIS; APOPTOSIS
AB Dysregulation of T-cell survival and apoptosis is the common cause of autoimmune diseases such as multiple sclerosis (MS). However, the factors inducing imbalance of T-cell survival and apoptosis in MS remains unclear. Here, we show that the resistance to apoptosis was associated with high levels of B-cell activating factor (BAFF). Blockade of BAFF with TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor)-IgG significantly reduced T-cell survival in myelin oligodendroglia glycoprotein (MOG)-induced chronic experimental allergic encephalitis (EAE). Furthermore, BAFF induced anti-apoptotic molecule Bcl2 expression in T cells by up-regulating osteopontin (OPN) secretion from B cells. BAFF mainly induced OPN expression in splenic CD21-CD23(+) B cells via a NF-kB dependent signaling pathway. In addition, we found that BAFF and OPN levels were increased in MS patients similar to the results obtained from our mice research. The study suggests that BAFF regulates T-cell survival by inducing OPN secretion in B cells in autoimmune diseases. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Ma, Ning; Xiao, He; Han, Gencheng; Chen, Guojiang; Wang, Yi; Wang, Ke; Hou, Chunmei; Yang, Xiaomei; Shen, Beifen; Li, Yan; Wang, Renxi] Inst Basic Med Sci, Immunol Lab, Beijing 100850, Peoples R China.
[Ma, Ning] Jilin Univ, Hosp 1, Dept Rheumatol, Changchun 130021, Peoples R China.
[He, Youdi] Capital Med Univ, Beijing Chaoyang Hosp, Dept Neurol, Beijing 100020, Peoples R China.
[Marrero, Bernadette] NEI, Mol Immunol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Wang, Yujuan] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Li, Y (reprint author), Inst Basic Med Sci, Immunol Lab, POB 130 3,Taiping Rd 27, Beijing 100850, Peoples R China.
EM liyan62033@yahoo.com.cn; wang_renxi@yahoo.com
RI wang, yujuan/C-8428-2016
FU National Basic Research Program 973 Grants [2013CB530506]; Beijing
Natural Science Foundation [7132139]
FX This study was supported by National Basic Research Program 973 Grants
(2013CB530506) and Beijing Natural Science Foundation (7132139).
NR 30
TC 6
Z9 6
U1 1
U2 6
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0161-5890
J9 MOL IMMUNOL
JI Mol. Immunol.
PD FEB
PY 2014
VL 57
IS 2
BP 129
EP 137
DI 10.1016/j.molimm.2013.08.014
PG 9
WC Biochemistry & Molecular Biology; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA 282BR
UT WOS:000329145800009
PM 24084099
ER
PT J
AU Whiley, L
Sen, A
Heaton, J
Proitsi, P
Garcia-Gomez, D
Leung, R
Smith, N
Thambisetty, M
Kloszewska, I
Mecocci, P
Soininen, H
Tsolaki, M
Vellas, B
Lovestone, S
Legido-Quigley, C
AF Whiley, Luke
Sen, Arundhuti
Heaton, James
Proitsi, Petroula
Garcia-Gomez, Diego
Leung, Rufina
Smith, Norman
Thambisetty, Madhav
Kloszewska, Iwona
Mecocci, Patrizia
Soininen, Hilkka
Tsolaki, Magda
Vellas, Bruno
Lovestone, Simon
Legido-Quigley, Cristina
CA AddNeuroMed Consortium
TI Evidence of altered phosphatidylcholine metabolism in Alzheimer's
disease
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Alzheimer's disease; Phosphatidylcholine; ApoE; Lipid; Plasma; Mild
cognitive impairment; Addneuromed
ID PHOSPHOLIPASE A(2) ACTIVITY; TANDEM MASS-SPECTROMETRY; COGNITIVE
IMPAIRMENT; PLASMA; LIPIDS; PROGRESSION; BIOMARKERS; MS; IDENTIFICATION;
SPECTROSCOPY
AB Abberant lipid metabolism is implicated in Alzheimer's disease (AD) pathophysiology, but the connections between AD and lipid metabolic pathways are not fully understood. To investigate plasma lipids in AD, a multiplatform screen (n = 35 by liquid chromatography-mass spectrometry and n = 35 by nuclear magnetic resonance) was developed, which enabled the comprehensive analysis of plasma from 3 groups (individuals with AD, individuals with mild cognitive impairment (MCI), and age-matched controls). This screen identified 3 phosphatidylcholine (PC) molecules that were significantly diminished in AD cases. In a subsequent validation study (n = 141), PC variation in a bigger sample set was investigated, and the same 3 PCs were found to be significantly lower in AD patients: PC 16:0/20: 5 (p < 0.001), 16:0/22: 6 (p < 0.05), and 18: 0/22: 6 (p < 0.01). A receiver operating characteristic (ROC) analysis of the PCs, combined with apolipoprotein E (ApoE) data, produced an area under the curve predictive value of 0.828. Confirmatory investigations into the background biochemistry indiciated no significant change in plasma levels of 3 additional PCs of similar structure, total choline containing compounds or total plasma omega fatty acids, adding to the evidence that specific PCs play a role in AD pathology. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Whiley, Luke; Sen, Arundhuti; Proitsi, Petroula; Leung, Rufina; Lovestone, Simon; Legido-Quigley, Cristina] Kings Coll London, Inst Pharmaceut Sci, London SE1 9NH, England.
[Whiley, Luke; Sen, Arundhuti; Proitsi, Petroula; Leung, Rufina; Lovestone, Simon; Legido-Quigley, Cristina] Kings Coll London, Inst Psychiat, London SE1 9NH, England.
[Heaton, James; Smith, Norman] Kings Coll London, Waters Ctr Innovat, London SE1 9NH, England.
[Garcia-Gomez, Diego] Univ Salamanca, Dept Analyt Chem, E-37008 Salamanca, Spain.
[Thambisetty, Madhav] NIA, Clin & Tanslat Neurosci Unit, Lab Behav Neurosci, Baltimore, MD 21224 USA.
[Kloszewska, Iwona] Med Univ Lodz, Dept Old Age Psychiat & Psychot Disorders, Lodz, Poland.
[Mecocci, Patrizia] Univ Perugia, Dept Clin & Expt Med, Sect Gerontol & Geriatr, I-06100 Perugia, Italy.
[Soininen, Hilkka] Univ Eastern Finland, Dept Neurol, Kuopio, Finland.
[Soininen, Hilkka] Kuopio Univ Hosp, SF-70210 Kuopio, Finland.
[Tsolaki, Magda] Aristotle Univ Thessaloniki, Dept Neurol 3, GR-54006 Thessaloniki, Greece.
[Vellas, Bruno] Hop Toulouse, Dept Internal & Geriatr Med, Toulouse, France.
RP Legido-Quigley, C (reprint author), Kings Coll London, Inst Pharmaceut Sci, 5th Flr,Franklin Wilkins Bldg,150 Stamford St, London SE1 9NH, England.
EM cristina.legido_quigley@kcl.ac.uk
RI Garcia-Gomez, Diego/Q-6311-2016;
OI Garcia-Gomez, Diego/0000-0001-5753-2962; Whiley,
Luke/0000-0002-9088-4799; Sen, Arundhuti/0000-0001-9599-472X
FU UK NHS National Institute of Health Research (NIHR) Biomedical Research
Centre (BRC) for mental health at the South London and Maudsley (SLaM);
European Commision (AddNeuroMed); Waters Centre of Excellence for Mass
Spectrometry at King's College London
FX Supported by the UK NHS National Institute of Health Research (NIHR)
Biomedical Research Centre (BRC) for mental health at the South London
and Maudsley (SLaM), the European Commision (AddNeuroMed) and the Waters
Centre of Excellence for Mass Spectrometry at King's College London. All
authors have reviewed and contributed to the writing of this manuscript.
NR 49
TC 39
Z9 40
U1 3
U2 42
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
EI 1558-1497
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD FEB
PY 2014
VL 35
IS 2
BP 271
EP 278
DI 10.1016/j.neurobiolaging.2013.08.001
PG 8
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 275DD
UT WOS:000328655600001
PM 24041970
ER
PT J
AU Kara, E
Xiromerisiou, G
Spanaki, C
Bozi, M
Koutsis, G
Panas, M
Dardiotis, E
Ralli, S
Bras, J
Letson, C
Edsall, C
Pliner, H
Arepalli, S
Kalinderi, K
Fidani, L
Bostantjopoulou, S
Keller, MF
Wood, NW
Hardy, J
Houlden, H
Stefanis, L
Plaitakis, A
Hernandez, D
Hadjigeorgiou, GM
Nalls, MA
Singleton, AB
AF Kara, Eleanna
Xiromerisiou, Georgia
Spanaki, Cleanthe
Bozi, Maria
Koutsis, Georgios
Panas, Marios
Dardiotis, Efthimios
Ralli, Styliani
Bras, Jose
Letson, Christopher
Edsall, Connor
Pliner, Hannah
Arepalli, Sampath
Kalinderi, Kallirhoe
Fidani, Liana
Bostantjopoulou, Sevasti
Keller, Margaux F.
Wood, Nicholas W.
Hardy, John
Houlden, Henry
Stefanis, Leonidas
Plaitakis, Andreas
Hernandez, Dena
Hadjigeorgiou, Georgios M.
Nalls, Mike A.
Singleton, Andrew B.
TI Assessment of Parkinson's disease risk loci in Greece
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Parkinson's disease; GWAS; GCTA; Genetics; Greece; Risk profiles
ID GENOME-WIDE ASSOCIATION; HEXANUCLEOTIDE REPEAT; EUROPEAN POPULATION;
HAPLOGROUP-J; LEWY BODY; VARIANTS; GENETICS; IDENTIFICATION;
COLONIZATION; HERITABILITY
AB Genome-wide association studies (GWAS) have been shown to be a powerful approach to identify risk loci for neurodegenerative diseases. Recent GWAS in Parkinson's disease (PD) have been successful in identifying numerous risk variants pointing to novel pathways potentially implicated in the pathogenesis of PD. Contributing to these GWAS efforts, we performed genotyping of previously identified risk alleles in PD patients and control subjects from Greece. We showed that previously published risk profiles for Northern European and American populations are also applicable to the Greek population. In addition, although our study was largely underpowered to detect individual associations, we replicated 5 of 32 previously published risk variants with nominal p values <0.05. Genome-wide complex trait analysis revealed that known risk loci explain disease risk in 1.27% of Greek PD patients. Collectively, these results indicate that there is likely a substantial genetic component to PD in Greece, similarly to other worldwide populations, that remains to be discovered. Published by Elsevier Inc.
C1 [Kara, Eleanna; Bras, Jose; Wood, Nicholas W.; Hardy, John; Houlden, Henry; Hernandez, Dena] UCL, Reta Lila Weston Labs, Inst Neurol, London, England.
[Kara, Eleanna; Bras, Jose; Wood, Nicholas W.; Hardy, John; Houlden, Henry; Hernandez, Dena] UCL, Dept Mol Neurosci, Inst Neurol, London, England.
[Xiromerisiou, Georgia; Dardiotis, Efthimios; Ralli, Styliani; Hadjigeorgiou, Georgios M.] Univ Thessaly, Fac Med, Dept Neurol, Neurogenet Lab, Larisa, Greece.
[Xiromerisiou, Georgia] Papageorgiou Hosp, Dept Neurol, Thessaloniki, Greece.
[Spanaki, Cleanthe; Plaitakis, Andreas] Univ Crete, Sch Med, Dept Neurol, Iraklion, Crete, Greece.
[Bozi, Maria] Gen Hosp Syros, Syros, Greece.
[Bozi, Maria] Hygeia Hosp, Clin Neurodegenerat Disorders, Athens, Greece.
[Bozi, Maria; Stefanis, Leonidas] Univ Athens, Dept Neurol 2, Sch Med, Athens 11528, Greece.
[Koutsis, Georgios; Panas, Marios] Univ Athens, Eginit Hosp, Sch Med, Neurogenet Unit,Dept Neurol 1, GR-11528 Athens, Greece.
[Letson, Christopher; Edsall, Connor; Pliner, Hannah; Arepalli, Sampath; Keller, Margaux F.; Hernandez, Dena; Singleton, Andrew B.] NIA, Neurogenet Lab, Bethesda, MD 20892 USA.
[Kalinderi, Kallirhoe; Fidani, Liana] Aristotle Univ Thessaloniki, Sch Med, Dept Gen Biol, GR-54124 Thessaloniki, Greece.
[Bostantjopoulou, Sevasti] Aristotle Univ Thessaloniki, G Papanikolaou Hosp, Dept Neurol 3, GR-54006 Thessaloniki, Greece.
[Keller, Margaux F.] Temple Univ, Dept Biol Anthropol, Philadelphia, PA 19122 USA.
[Stefanis, Leonidas] Acad Athens, Biomed Res Fdn, Div Basic Neurosci, Athens, Greece.
RP Singleton, AB (reprint author), NIA, NIH, Mol Genet Sect, Bldg 35,Room 1A1014,35 Convent Dr, Bethesda, MD 20892 USA.
EM Singleta@mail.nih.gov
RI Kara, Eleanna/E-1630-2013; Hardy, John/C-2451-2009; Singleton,
Andrew/C-3010-2009; Houlden, Henry/C-1532-2008; Bras, Jose/A-1428-2011;
Pliner, Hannah/F-3608-2015; Wood, Nicholas/C-2505-2009
OI Bras, Jose/0000-0001-8186-0333; Houlden, Henry/0000-0002-2866-7777;
Pliner, Hannah/0000-0003-1484-6501; Wood, Nicholas/0000-0002-9500-3348
FU Parkinson's disease foundation; Wellcome Trust; Medical Research Council
(MRC); Wellcome Trust/MRC Joint Call in Neurodegeneration award
[WT089698]; Intramural Research Programs of the National Institute on
Aging [Z01 AG000949-02]; National Institute for Health Research
University College London Hospitals Biomedical Research Centre; Research
Committee, University of Thessaly
FX The authors thank the patients and their families for their essential
help, Mark Gaskin (University College London; UCL) and Dr Matina Maniati
(Bioacademy of Athens, Greece) for help with sample organization,
Hallgeir Jonvik (UCL) and Rick Santmier (National Institutes of Health;
NIH) for help with data management and IT support, and June Smalley
(UCL), Joan Ward (NIH), and Kimberly Singleton (NIH) for administrative
assistance. This work was supported by the Parkinson's disease
foundation (GX, HH), the Wellcome Trust, the Medical Research Council
(MRC), and by the Wellcome Trust/MRC Joint Call in Neurodegeneration
award (WT089698) to the UK Parkinson's Disease Consortium whose members
are from the UCL Institute of Neurology, the University of Sheffield,
and the MRC Protein Phosphorylation Unit at the University of Dundee.
This work was supported in part by the Intramural Research Programs of
the National Institute on Aging, Z01 AG000949-02. The authors are
grateful to The Queen Square brain bank, The Netherlands brain bank, The
Harvard Brain Tissue Resource Centre, University of Maryland Brain and
Tissue Bank for Developmental Disorders, and the MRC London Brain Bank.
This study was supported by the National Institute for Health Research
University College London Hospitals Biomedical Research Centre. This
study used the high-performance computational capabilities of the
Biowulf Linux cluster at the National Institutes of Health, Bethesda,
Maryland (http://biowulf.nih.gov). This study was supported in part by
Research Committee, University of Thessaly (code 2845; PI: GMH).
NR 43
TC 2
Z9 2
U1 0
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
EI 1558-1497
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD FEB
PY 2014
VL 35
IS 2
AR 442. e9
DI 10.1016/j.neurobiolaging.2013.07.011
PG 8
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 275DD
UT WOS:000328655600021
PM 24080174
ER
PT J
AU Tranah, GJ
Yokoyama, JS
Katzman, SM
Nalls, MA
Newman, AB
Harris, TB
Cesari, M
Manini, TM
Schork, NJ
Cummings, SR
Liu, Y
Yaffe, K
AF Tranah, Gregory J.
Yokoyama, Jennifer S.
Katzman, Shana M.
Nalls, Michael A.
Newman, Anne B.
Harris, Tamara B.
Cesari, Matteo
Manini, Todd M.
Schork, Nicholas J.
Cummings, Steven R.
Liu, Yongmei
Yaffe, Kristine
CA Hlth Aging and Body Composition
TI Mitochondrial DNA sequence associations with dementia and amyloid-beta
in elderly African Americans
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Dementia; Mitochondria; mtDNA; Amyloid-beta; Oxidative stress
ID ALPHA-KETOGLUTARATE DEHYDROGENASE; ACTIVITY ENERGY-EXPENDITURE; MILD
COGNITIVE IMPAIRMENT; AMINO-ACID SUBSTITUTIONS; INDUCED OXIDATIVE
STRESS; GENOME-WIDE ASSOCIATION; ALZHEIMERS-DISEASE; CALORIE
RESTRICTION; BODY-COMPOSITION; POINT MUTATIONS
AB Mitochondrial dysfunction occurs early in the course of several neurodegenerative diseases, and is potentially related to increased oxidative damage and amyloid-beta (A beta) formation in Alzheimer's disease. The goals of this study were to assess mtDNA sequence associations with dementia risk, 10-year cognitive change, and markers of oxidative stress and A beta among 1089 African-Americans in the population-based Health, Aging, and Body Composition Study. Participants were free of dementia at baseline, and incidence was determined in 187 (18%) cases over 10 to 12 follow-up years. Haplogroup L1 participants were at increased risk for developing dementia (odds ratio = 1.88, 95% confidence interval = 1.23-2.88, p = 0.004), lower plasma A beta 42 levels (p = 0.03), and greater 10-year decline on the Digit Symbol Substitution Test (p = 0.04) when compared with common haplogroup L3. The p.V193I, ND2 substitution was associated with significantly higher A beta 42 levels (p = 0.0012), and this association was present in haplogroup L3 (p = 0.018) but not L1 (p = 0.90) participants. All associations were independent of potential confounders, including APOE epsilon 4 status and nuclear genetic ancestry. Identification of mtDNA sequence variation associated with dementia risk and cognitive decline may contribute to the development of new treatment targets and diagnostic tests that identify responders to interventions targeting mitochondria. (C) 2014 Published by Elsevier Inc.
C1 [Tranah, Gregory J.; Cummings, Steven R.] Calif Pacific Med Ctr, Res Inst San Francisco, San Francisco, CA USA.
[Yokoyama, Jennifer S.] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94143 USA.
[Katzman, Shana M.] Buck Inst Res Aging, Novato, CA USA.
[Nalls, Michael A.] NIA, Neurogenet Lab, Intramural Res Program, Bethesda, MD 20892 USA.
[Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Cesari, Matteo] Ctr Hospitalier Univ Toulouse, INSERM UMR 1027, Gerontopole, Toulouse, France.
[Manini, Todd M.] Univ Florida, Dept Aging & Geriatr Res, Gainesville, FL USA.
[Schork, Nicholas J.] Scripps Translat Sci Inst, La Jolla, CA USA.
[Liu, Yongmei] Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA USA.
[Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA.
RP Tranah, GJ (reprint author), UCSF, San Francisco Coordinating Ctr, Res Inst, Calif Pacific Med Ctr, 185 Berry St,Lobby 5,Suite 5700, San Francisco, CA 94107 USA.
EM gtranah@sfcc-cpmc.edu
RI Cesari, Matteo/A-4649-2008; Newman, Anne/C-6408-2013
OI Cesari, Matteo/0000-0002-0348-3664; Newman, Anne/0000-0002-0106-1150
FU National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103,
N01-AG-6-2106, R01-AG028050, R03-AG032498, 1R01AG032098-01A1]; NINR
grant [R01-NR012459, Z01AG000951]; Intramural Research Program of the
NIH, National Institute on Aging; National Institutes of Health
[HHSN268200782096C]
FX This research was supported by National Institute on Aging (NIA)
Contracts N01-AG-6-2101; N01-AG-6-2103; N01-AG-6-2106; NIA grants
R01-AG028050 and R03-AG032498, NINR grant R01-NR012459; and Z01AG000951.
This research was supported in part by the Intramural Research Program
of the NIH, National Institute on Aging. The genome-wide association
study was funded by NIA grant 1R01AG032098-01A1 to Wake Forest
University Health Sciences and genotyping services were provided by the
Center for Inherited Disease Research (CIDR). CIDR is fully funded
through a federal contract from the National Institutes of Health to
Johns Hopkins University, contract number HHSN268200782096C. Data
analyses for this study used the high-performance computational
capabilities of the Biowulf Linux cluster at the National Institutes of
Health, Bethesda, MD (http://biowulf.nih.gov).
NR 120
TC 6
Z9 6
U1 0
U2 18
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
EI 1558-1497
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD FEB
PY 2014
VL 35
IS 2
AR 442.e1
DI 10.1016/j.neurobiolaging.2013.05.023
PG 8
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 275DD
UT WOS:000328655600020
PM 24140124
ER
PT J
AU Hyland, PL
Lin, SW
Hu, N
Zhang, H
Wang, LM
Su, H
Wang, CY
Ding, T
Tang, ZZ
Fan, JH
Qiao, YL
Xiong, XQ
Wheeler, W
Giffen, C
Yu, K
Yuenger, J
Burdett, L
Wang, ZM
Chanock, SJ
Tucker, MA
Dawsey, SM
Freedman, ND
Goldstein, AM
Abnet, CC
Taylor, PR
AF Hyland, Paula L.
Lin, Shih-Wen
Hu, Nan
Zhang, Han
Wang, Lemin
Su, Hua
Wang, Chaoyu
Ding, Ti
Tang, Ze-Zhong
Fan, Jin-Hu
Qiao, You-Lin
Xiong, Xiaoqin
Wheeler, William
Giffen, Carol
Yu, Kai
Yuenger, Jeff
Burdett, Laurie
Wang, Zhaoming
Chanock, Stephen J.
Tucker, Margaret A.
Dawsey, Sanford M.
Freedman, Neal D.
Goldstein, Alisa M.
Abnet, Christian C.
Taylor, Philip R.
TI Genetic variants in Fas signaling pathway genes and risk of gastric
cancer
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE gastric cancer; gastric cardia; gastric noncardia; Fas signaling;
genetic variants; GWAS; single nucleotide polymorphisms; pathway genes
ID GENOME-WIDE ASSOCIATION; SQUAMOUS-CELL CARCINOMA; KINASE CATALYTIC
SUBUNIT; MEDIATED APOPTOSIS; HELICOBACTER-PYLORI; SUSCEPTIBILITY LOCI;
T-CELLS; ESOPHAGEAL; PROTEIN; ADENOCARCINOMA
AB Populations in north central China are at high risk for gastric cancers (GC), and altered FAS-mediated cell signaling and/or apoptosis may contribute to this risk. We examined the association of 554 single nucleotide polymorphisms (SNPs) in 53 Fas signaling-related genes using a pathway-based approach in 1758 GC cases (1126 gastric cardia adenocarcinomas (GCA) and 632 gastric noncardia adenocarcinomas (GNCA)), and 2111 controls from a genome-wide association study (GWAS) of GC in ethnic Chinese. SNP associations with risk of overall GC, GCA and GNCA were evaluated using unconditional logistic regressions controlling for age, sex and study. Gene- and pathway-based associations were tested using the adaptive rank-truncated product (ARTP) method. Statistical significance was evaluated empirically by permutation. Significant pathway-based associations were observed for Fas signaling with risk of overall GC (p = 5.5E-04) and GCA (p = 6.3E-03), but not GNCA (p= 8.1E-02). Among examined genes in the Fas signaling pathway, MAP2K4, FAF1, MAPK8, CASP10, CASP8, CFLAR, MAP2K1, CAP8AP2, PAK2 and IKBKB were associated with risk of GC (nominal p < 0.05), and FAF1 and MAPK8 were significantly associated with risk of both GCA and GNCA (nominal p< 0.05). Our examination of genetic variation in the Fas signaling pathway is consistent with an association of altered Fas signaling and/or apoptosis with risk of GC. As one of the first attempts to investigate a pathway-level association, our results suggest that these genes and the Fas signaling pathway warrant further evaluation in relation to GC risk in other populations.
C1 [Hyland, Paula L.; Hu, Nan; Wang, Lemin; Su, Hua; Wang, Chaoyu; Goldstein, Alisa M.; Taylor, Philip R.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Hyland, Paula L.; Lin, Shih-Wen] NCI, Canc Prevent Fellowship Program, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Lin, Shih-Wen; Dawsey, Sanford M.; Freedman, Neal D.; Abnet, Christian C.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Zhang, Han; Yu, Kai] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Ding, Ti; Tang, Ze-Zhong] Shanxi Canc Hosp, Taiyuan, Peoples R China.
[Fan, Jin-Hu; Qiao, You-Lin] Chinese Acad Med Sci, Dept Epidemiol, Canc Inst Hosp, Beijing 100730, Peoples R China.
[Xiong, Xiaoqin; Wheeler, William; Giffen, Carol] Informat Management Serv Inc, Silver Spring, MD USA.
[Yuenger, Jeff; Burdett, Laurie; Wang, Zhaoming; Chanock, Stephen J.] NCI Frederick, Core Genotyping Facil, SAIC Frederick Inc, Bethesda, MD USA.
[Yuenger, Jeff; Burdett, Laurie; Wang, Zhaoming; Chanock, Stephen J.] Div Canc Epidemiol & Genet, Bethesda, MD USA.
[Tucker, Margaret A.] NCI, Human Genet Program, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Hyland, PL (reprint author), NIH, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bldg 10, Bethesda, MD 20892 USA.
EM hylandpl@mail.nih.gov
RI Qiao, You-Lin/B-4139-2012; Tucker, Margaret/B-4297-2015; Abnet,
Christian/C-4111-2015; Freedman, Neal/B-9741-2015; Zhang,
Han/K-2118-2016
OI Qiao, You-Lin/0000-0001-6380-0871; Abnet, Christian/0000-0002-3008-7843;
Freedman, Neal/0000-0003-0074-1098; Zhang, Han/0000-0001-7977-9616
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Division of Cancer Epidemiology and Genetics;
Cancer Prevention Fellowship Program, Division of Cancer Prevention,
National Cancer Institute, Bethesda, USA; Health and Social Care (HSC),
Northern Ireland, UK
FX Grant sponsors: Intramural Research Program of the National Institutes
of Health, National Cancer Institute, Division of Cancer Epidemiology
and Genetics; Cancer Prevention Fellowship Program, Division of Cancer
Prevention, National Cancer Institute, Bethesda, USA, Health and Social
Care (HSC), Northern Ireland, UK
NR 54
TC 9
Z9 11
U1 2
U2 17
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 FEB
PY 2014
VL 134
IS 4
BP 822
EP 831
DI 10.1002/ijc.28415
PG 10
WC Oncology
SC Oncology
GA 264OX
UT WOS:000327889700010
PM 23921907
ER
PT J
AU Camargo, MC
Koriyama, C
Matsuo, K
Kim, WH
Herrera-Goepfert, R
Liao, LM
Yu, J
Carrasquilla, G
Sung, JJY
Alvarado-Cabrero, I
Lissowska, J
Meneses-Gonzalez, F
Yatabe, Y
Ding, T
Hu, N
Taylor, PR
Morgan, DR
Gulley, ML
Torres, J
Akiba, S
Rabkin, CS
AF Camargo, M. Constanza
Koriyama, Chihaya
Matsuo, Keitaro
Kim, Woo-Ho
Herrera-Goepfert, Roberto
Liao, Linda M.
Yu, Jun
Carrasquilla, Gabriel
Sung, Joseph J. Y.
Alvarado-Cabrero, Isabel
Lissowska, Jolanta
Meneses-Gonzalez, Fernando
Yatabe, Yashushi
Ding, Ti
Hu, Nan
Taylor, Philip R.
Morgan, Douglas R.
Gulley, Margaret L.
Torres, Javier
Akiba, Suminori
Rabkin, Charles S.
CA Eurgast-EPIC Grp
TI Case-case comparison of smoking and alcohol risk associations with
Epstein-Barr virus-positive gastric cancer
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE alcohol; EBV; gastric cancer; smoking; pooled-analysis
ID HELICOBACTER-PYLORI INFECTION; CARCINOMA; METAANALYSIS; ADENOCARCINOMA;
PROTEIN; COHORT; JAPAN
AB Helicobacter pylori is the primary cause of gastric cancer. However, monoclonal Epstein-Barr virus (EBV) nucleic acid is also present in up to 10% of these tumors worldwide. EBV prevalence is increased with male sex, nonantral localization and surgically disrupted anatomy. To further examine associations between EBV and gastric cancer, we organized an international consortium of 11 studies with tumor EBV status assessed by in situ hybridization. We pooled individual-level data on 2,648 gastric cancer patients, including 184 (7%) with EBV-positive cancers; all studies had information on cigarette use (64% smokers) and nine had data on alcohol (57% drinkers). We compared patients with EBV-positive and EBV-negative tumors to evaluate smoking and alcohol interactions with EBV status. To account for within-population clustering, multilevel logistic regression models were used to estimate interaction odds ratios (OR) adjusted for distributions of sex (72% male), age (mean 59 years), tumor histology (56% Lauren intestinal-type), anatomic subsite (61% noncardia) and year of diagnosis (1983-2012). In unadjusted analyses, the OR of EBV positivity with smoking was 2.2 [95% confidence interval (CI) 1.6-3.2]. The OR was attenuated to 1.5 (95% CI 1.01-2.3) by adjustment for the possible confounders. There was no significant interaction of EBV status with alcohol drinking (crude OR 1.4; adjusted OR 1.0). Our data indicate the smoking association with gastric cancer is stronger for EBV-positive than EBV-negative tumors. Conversely, the null association with alcohol does not vary by EBV status. Distinct epidemiologic characteristics of EBV-positive cancer further implicate the virus as a cofactor in gastric carcinogenesis.
C1 [Camargo, M. Constanza; Liao, Linda M.; Hu, Nan; Taylor, Philip R.; Rabkin, Charles S.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20850 USA.
[Koriyama, Chihaya; Akiba, Suminori] Kagoshima Univ, Grad Sch Med & Dent Sci, Kagoshima 890, Japan.
[Matsuo, Keitaro] Kyushu Univ, Fac Med Sci, Dept Prevent Med, Fukuoka 812, Japan.
[Kim, Woo-Ho] Seoul Natl Univ, Coll Med, Dept Pathol, Seoul 151, South Korea.
[Herrera-Goepfert, Roberto] Natl Canc Inst, Dept Pathol, Mexico City, DF, Mexico.
[Yu, Jun; Sung, Joseph J. Y.] Chinese Univ Hong Kong, Dept Med & Therapeut, Inst Digest Dis, Li Ka Shing Inst Hlth Sci, Hong Kong, Hong Kong, Peoples R China.
[Carrasquilla, Gabriel] Fdn Santa Fe Bogota, Ctr Estudios & Invest Salud, Bogota, Colombia.
[Alvarado-Cabrero, Isabel] Inst Mexicano Seguro Social, UMAE Oncol, CMN SXXI, Serv Patol, Mexico City, DF, Mexico.
[Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr, Div Canc Epidemiol & Prevent, Warsaw, Poland.
[Lissowska, Jolanta] Inst Oncol, Warsaw, Poland.
[Meneses-Gonzalez, Fernando] Secretaria Salud Mexico, Direcc Gen Adjunta Epidemiol, Programa Residencia Epidemiol, Mexico City, DF, Mexico.
[Yatabe, Yashushi] Aichi Canc Ctr Hosp, Dept Pathol & Mol Diagnost, Nagoya, Aichi 464, Japan.
[Ding, Ti] Shanxi Canc Hosp, Taiyuan, Shanxi, Peoples R China.
[Morgan, Douglas R.] Vanderbilt Univ, Sch Med, Dept Med, Div Gastroenterol Hepatol & Nutr, Nashville, TN 37212 USA.
[Morgan, Douglas R.] Univ N Carolina, Div Gastroenterol, Chapel Hill, NC USA.
[Gulley, Margaret L.] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC USA.
[Gulley, Margaret L.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Torres, Javier] Inst Mexicano Seguro Social, CMN SXXI, UMAE Pediat, Unidad Invest Enfermedades Infecciosas, Mexico City, DF, Mexico.
RP Camargo, MC (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr,BG 9609-6E206, Rockville, MD 20850 USA.
EM camargomc@mail.nih.gov
RI Yu, Jun /D-8569-2015; Camargo, M. Constanza/R-9891-2016;
OI Liao, Linda/0000-0002-1923-5294; Lissowska, Jolanta/0000-0003-2695-5799;
Matsuo, Keitaro/0000-0003-1761-6314
FU Intramural Research Program of the United States National Institutes of
Health, National Cancer Institute; Japanese Ministry of Education,
Culture, Sports, Science and Technology [17015018, 221S0001]; JSPS A3
Foresight Program; Spanish Ministry of Health [PI070130, PI081420];
European Commission FP5 [QLG1-CT-2001-01049]; Spanish Ministry of Health
network RTICCC [ISCIII RD06/0020/0091]; Research Fund for the Control of
Infectious Diseases, RFCID, Hong Kong [11100022]; CONACYT, Mexico
[2007-69450]; United States National Institutes of Health [CA125588, P30
DK034987]
FX This work was supported in part by the Intramural Research Program of
the United States National Institutes of Health, National Cancer
Institute. The Hospital-based Epidemiologic Research Program at Aichi
Cancer Center II was supported by Grant-in-Aid for Scientific Research
on Priority Areas of Cancer (No. 17015018) and on Innovative Areas (No.
221S0001) from the Japanese Ministry of Education, Culture, Sports,
Science and Technology and JSPS A3 Foresight Program. The Eurgast-EPIC
study was supported by the Health Research Fund of the Spanish Ministry
of Health (exp. PI070130 and PI081420); European Commission FP5 (ref.
QLG1-CT-2001-01049); and Spanish Ministry of Health network RTICCC
(ISCIII RD06/0020/0091. The Chinese study in Guangzhou was supported by
the Research Fund for the Control of Infectious Diseases, RFCID, Hong
Kong (No. 11100022). The study at IMSS was partially funded by CONACYT,
Mexico (Grant No. 2007-69450). The Honduras study was supported by the
United States National Institutes of Health (CA125588, DRM; P30
DK034987).
NR 37
TC 12
Z9 13
U1 0
U2 11
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 FEB
PY 2014
VL 134
IS 4
BP 948
EP 953
DI 10.1002/ijc.28402
PG 6
WC Oncology
SC Oncology
GA 264OX
UT WOS:000327889700023
PM 23904115
ER
PT J
AU Felix, AS
Weissfeld, JL
Pfeiffer, RM
Modugno, F
Black, A
Hill, LM
Martin, J
Sit, AS
Sherman, ME
Brinton, LA
AF Felix, Ashley S.
Weissfeld, Joel L.
Pfeiffer, Ruth M.
Modugno, Francesmary
Black, Amanda
Hill, Lyndon M.
Martin, Jerry
Sit, Anita S.
Sherman, Mark E.
Brinton, Louise A.
TI Endometrial thickness and risk of breast and endometrial carcinomas in
the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE transvaginal ultrasound; screening; etiology; cancer risk; endometrial
thickness
ID ASYMPTOMATIC POSTMENOPAUSAL WOMEN; BODY-MASS INDEX; ULTRASOUND; WEIGHT
AB Postmenopausal women with higher circulating estrogen levels are at increased risk of developing breast and endometrial carcinomas. In the endometrium, excess estrogen relative to progesterone produces a net proliferative stimulus, which may result in endometrial thickening. Therefore, the hypothesis that endometrial thickness is a biological marker of excess estrogen stimulation that is associated with risk of breast and endometrial carcinomas was tested. Endometrial thickness was measured in 1,272 postmenopausal women, aged 55-74 years, who underwent transvaginal ultrasound (TVU) screening as part of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Serial endometrial thickness measurements were available for a subset of women at 1 year (n=1,018), 2 years (n=869) and 3 years (n=641) after baseline. The associations between endometrial thickness and breast (n=91) and endometrial (n=14) carcinoma were evaluated by estimating relative risks (RRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression with age as the time metric. Models incorporating baseline endometrial thickness and as a time-varying covariate using all measurements were examined. Median follow-up among study participants was 12.5 years (range: 0.3-13.8 years). Compared to baseline endometrial thickness of 1.0-2.99 mm, women with baseline endometrial thickness greater than or equal to 5.0 mm had an increased risk of breast (RR=2.00, 95% CI=1.15-3.48) and endometrial (RR=5.02, 95% CI=0.96-26.36) carcinomas in models adjusted for menopausal hormone use and BMI. These data suggest that increased endometrial thickness as assessed by TVU was associated with increased risk of breast and endometrial carcinomas.
C1 [Felix, Ashley S.] NCI, Canc Prevent Fellowship Program, Canc Prevent Div, NIH, Rockville, MD USA.
[Felix, Ashley S.; Sherman, Mark E.; Brinton, Louise A.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Weissfeld, Joel L.; Modugno, Francesmary] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Pfeiffer, Ruth M.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Modugno, Francesmary] Magee Womens Res Inst, Womens Canc Res Program, Pittsburgh, PA USA.
[Modugno, Francesmary] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
[Modugno, Francesmary] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA.
[Black, Amanda] NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Hill, Lyndon M.; Martin, Jerry] Univ Pittsburgh, Magee Womens Hosp, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15213 USA.
[Sit, Anita S.] Santa Clara Valley Med Ctr, Dept Obstet & Gynecol, San Jose, CA 95128 USA.
RP Felix, AS (reprint author), NCI, Canc Prevent Fellowship Program, Canc Prevent Div, NIH, Rockville, MD USA.
EM ashley.felix@gmail.com
RI Brinton, Louise/G-7486-2015; Felix, Ashley/A-3240-2016
OI Brinton, Louise/0000-0003-3853-8562;
FU Intramural NIH HHS [Z99 CA999999]
NR 18
TC 1
Z9 1
U1 0
U2 20
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 FEB
PY 2014
VL 134
IS 4
BP 954
EP 960
DI 10.1002/ijc.28404
PG 7
WC Oncology
SC Oncology
GA 264OX
UT WOS:000327889700024
PM 23907658
ER
PT J
AU Spitzner, M
Roesler, B
Bielfeld, C
Emons, G
Gaedcke, J
Wolff, HA
Rave-Frank, M
Kramer, F
Beissbarth, T
Kitz, J
Wienands, J
Ghadimi, BM
Ebner, R
Ried, T
Grade, M
AF Spitzner, Melanie
Roesler, Birte
Bielfeld, Christian
Emons, Georg
Gaedcke, Jochen
Wolff, Hendrik A.
Rave-Fraenk, Margret
Kramer, Frank
Beissbarth, Tim
Kitz, Julia
Wienands, Juergen
Ghadimi, B. Michael
Ebner, Reinhard
Ried, Thomas
Grade, Marian
TI STAT3 inhibition sensitizes colorectal cancer to chemoradiotherapy in
vitro and in vivo
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE rectal cancer; chemoradiotherapy-resistance;
chemoradiotherapy-sensitization; STAT3; molecular target
ID COLON-CARCINOMA CELLS; RECTAL-CANCER; TUMOR MICROENVIRONMENT; SIGNAL
TRANSDUCER; TRANSCRIPTIONAL DEREGULATION; INTESTINAL INFLAMMATION;
ACTIVATION; EXPRESSION; RADIOTHERAPY; APOPTOSIS
AB Increased activity of signal transducer and activator of transcription 3 (STAT3) is common in human malignancies, including colorectal cancers (CRCs). We have recently reported that STAT3 gene expression correlates with resistance of CRC cell lines to 5-fluorouracil (5-FU)-based chemoradiotherapy (CT/RT). This is of considerable clinical importance, because a large proportion of rectal cancers are resistant to preoperative multimodal treatment. To test whether STAT3 contributes to CT/RT-resistance, we first confirmed that STAT3 protein expression correlated positively with increasing resistance. While STAT3 was not constitutively active, stimulation with interleukin-6 (IL-6) resulted in remarkably higher expression levels of phosphorylated STAT3 in CT/RT-resistant cell lines. A similar result was observed when we determined IL-6-induced expression levels of phosphorylated STAT3 following irradiation. Next, STAT3 was inhibited in SW480 and SW837 using siRNA, shRNA and the small-molecule inhibitor STATTIC. Successful silencing and inhibition of phosphorylation was confirmed using Western blot analysis and a luciferase reporter assay. RNAi-mediated silencing as well as STATTIC treatment resulted in significantly decreased clonogenic survival following exposure to 3 mu M of 5-FU and irradiation in a dose-dependent manner, with dose-modifying factors of 1.3-2.5 at a surviving fraction of 0.37. Finally, STAT3 inhibition led to a profound CT/RT-sensitization in a subcutaneous xenograft model, with a significantly delayed tumor regrowth in STATTIC-treated mice compared with control animals. These results highlight a potential role of STAT3 in mediating treatment resistance and provide first proof of concept that STAT3 represents a promising novel molecular target for sensitizing resistant rectal cancers to CT/RT.
What's new? A considerable percentage of rectal cancers are resistant to preoperative chemoradiotherapy, which exposes patients to the potential side effects of both irradiation and chemotherapy without clear benefits. In this study, IL-6-stimulated expression levels of phosphorylated STAT3 were remarkably higher in chemoradiotherapy-resistant colorectal cancer cell lines. RNAi- and small molecule-mediated STAT3 inhibition sensitized to chemoradiotherapy in vitro in a dose-dependent manner, which led to a profound chemoradiotherapy-sensitization in a subcutaneous xenograft model. These results highlight a potential role of STAT3 in treatment resistance, and provide first proof of concept that STAT3 represents a promising novel molecular target for sensitizing resistant rectal cancers to chemoradiotherapy.
C1 [Spitzner, Melanie; Roesler, Birte; Bielfeld, Christian; Emons, Georg; Gaedcke, Jochen; Ghadimi, B. Michael; Grade, Marian] Univ Med Gottingen, Dept Gen & Visceral Surg, D-37075 Gottingen, Germany.
[Wolff, Hendrik A.; Rave-Fraenk, Margret] Univ Med Gottingen, Dept Radiotherapy & Radiooncol, D-37075 Gottingen, Germany.
[Kramer, Frank; Beissbarth, Tim] Univ Med Gottingen, Dept Med Stat, D-37075 Gottingen, Germany.
[Kitz, Julia] Univ Med Gottingen, Dept Pathol, D-37075 Gottingen, Germany.
[Wienands, Juergen] Univ Med Gottingen, Dept Cellular & Mol Immunol, D-37075 Gottingen, Germany.
[Ebner, Reinhard; Ried, Thomas] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Grade, M (reprint author), Univ Med Gottingen, Dept Gen & Visceral Surg, Robert Koch Str 40, D-37075 Gottingen, Germany.
EM mgrade@uni-goettingen.de
FU Deutsche Forschungsgemeinschaf [KFO 179: GR 3376/1-1, GR 3376/1-2]
FX Grant sponsor: Deutsche Forschungsgemeinschaft; Grant numbers: KFO 179:
GR 3376/1-1, GR 3376/1-2
NR 50
TC 18
Z9 19
U1 0
U2 30
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 FEB
PY 2014
VL 134
IS 4
BP 997
EP 1007
DI 10.1002/ijc.28429
PG 11
WC Oncology
SC Oncology
GA 264OX
UT WOS:000327889700029
PM 23934972
ER
PT J
AU Cinquin, BP
Do, M
McDermott, G
Walters, AD
Myllys, M
Smith, EA
Cohen-Fix, O
Le Gros, MA
Larabell, CA
AF Cinquin, Bertrand P.
Do, Myan
McDermott, Gerry
Walters, Alison D.
Myllys, Markko
Smith, Elizabeth A.
Cohen-Fix, Orna
Le Gros, Mark A.
Larabell, Carolyn A.
TI Putting Molecules in Their Place
SO JOURNAL OF CELLULAR BIOCHEMISTRY
LA English
DT Article
DE CORRELATED; IMAGING; FLUORESCENCE; MICROSCOPY; SOFT X-RAY; TOMOGRAPHY
ID X-RAY MICROSCOPY; CRYO-LIGHT MICROSCOPY; ELECTRON-MICROSCOPY;
CORRELATIVE MICROSCOPY; CRYOELECTRON TOMOGRAPHY; FLUORESCENT PROTEINS;
BIOLOGICAL-MATERIALS; CELLS; SUPERRESOLUTION; ARCHITECTURE
AB Each class of microscope is limited to imaging specific aspects of cell structure and/or molecular organization. However, imaging the specimen by complementary microscopes and correlating the data can overcome this limitation. Whilst not a new approach, the field of correlative imaging is currently benefitting from the emergence of new microscope techniques. Here we describe the correlation of cryogenic fluorescence tomography (CFT) with soft X-ray tomography (SXT). This amalgamation of techniques integrates 3D molecular localization data (CFT) with a high-resolution, 3D cell reconstruction of the cell (SXT). Cells are imaged in both modalities in a near-native, cryopreserved state. Here we describe the current state of the art in correlative CFT-SXT, and discuss the future outlook for this method. J. Cell. Biochem. 115: 209-216, 2014. (c) 2013 Wiley Periodicals, Inc.
C1 [Cinquin, Bertrand P.; Do, Myan; McDermott, Gerry; Smith, Elizabeth A.; Le Gros, Mark A.; Larabell, Carolyn A.] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA.
[Walters, Alison D.; Cohen-Fix, Orna] NIDDK, NIH, Bethesda, MD 20892 USA.
[Myllys, Markko] Univ Jyvaskyla, Dept Phys, Jyvaskyla, Finland.
[Le Gros, Mark A.; Larabell, Carolyn A.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Phys Biosci Div, Berkeley, CA 94720 USA.
RP Larabell, CA (reprint author), Univ Calif San Francisco, Dept Anat, 1550,4th St,Box 2722, San Francisco, CA 94143 USA.
EM carolyn.larabell@ucsf.edu
FU NIH-NIGMS [P41 GM103445]; US DOE-BER [DE-AC02-05CH11231]; NIH-NIDDK
[Intramural]
FX Grant sponsor: NIH-NIGMS; Grant number: P41 GM103445; Grant sponsor: US
DOE-BER; Grant number: DE-AC02-05CH11231; Grant sponsor: NIH-NIDDK;
Grant number: Intramural.
NR 55
TC 12
Z9 13
U1 0
U2 17
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0730-2312
EI 1097-4644
J9 J CELL BIOCHEM
JI J. Cell. Biochem.
PD FEB
PY 2014
VL 115
IS 2
BP 209
EP 216
DI 10.1002/jcb.24658
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 271XF
UT WOS:000328424200001
PM 23966233
ER
PT J
AU Murphy, AJ
Pierce, J
de Caestecker, C
Libes, J
Neblett, D
de Caestecker, M
Perantoni, AO
Tanigawa, S
Anderson, JR
Dome, JS
Das, A
Carroll, TJ
Lovvorn, HN
AF Murphy, Andrew J.
Pierce, Janene
de Caestecker, Christian
Libes, Jaime
Neblett, David
de Caestecker, Mark
Perantoni, Alan O.
Tanigawa, Shunsuke
Anderson, James R.
Dome, Jeffrey S.
Das, Amrita
Carroll, Thomas J.
Lovvorn, Harold N., III
TI Aberrant Activation, Nuclear Localization, and Phosphorylation of
Yes-Associated Protein-1 in the Embryonic Kidney and Wilms Tumor
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE anaplasia; biomarker; nephrogenic rests; Wilms tumor; YAP1
ID CHILDRENS ONCOLOGY GROUP; HIPPO PATHWAY; GENE-EXPRESSION; SELF-RENEWAL;
YAP; CARCINOMA; CANCER; MUTATIONS; EFFECTORS; CITED1
AB BackgroundThe Yes-associated-protein-1 (YAP1) is a novel, direct regulator of stem cell genes both in development and cancer. FAT4 is an upstream regulator that induces YAP1 cytosolic sequestering by phosphorylation (p-Ser 127) and therefore inhibits YAP1-dependent cellular proliferation. We hypothesized that loss of FAT4 signaling would result in expansion of the nephron progenitor population in kidney development and that YAP1 subcellular localization would be dysregulated in Wilms tumor (WT), an embryonal malignancy that retains gene expression profiles and histologic features reminiscent of the embryonic kidney.
MethodsFetal kidneys from Fat4(-/-) mice were harvested at e18.5 and markers of nephron progenitors were investigated using immunohistochemical analysis. To examine YAP1 subcellular localization in WT, a primary WT cell line (VUWT30) was analyzed by immunofluorescence. Forty WT specimens evenly distributed between favorable and unfavorable histology (n=20 each), and treatment failure or success (n=20 each) was analyzed for total and phosphorylated YAP1 using immunohistochemistry and Western blot.
ResultsFat4(-/-) mouse fetal kidneys exhibit nuclear YAP1 with increased proliferation and expansion of nephron progenitor cells. In contrast to kidney development, subcellular localization of YAP1 is dysregulated in WT, with a preponderance of nuclear p-YAP1. By Western blot, median p-YAP1 quantity was 5.2-fold greater in unfavorable histology WT (P=0.05).
ConclusionsFetal kidneys in Fat4(-/-) mice exhibit a phenotype reminiscent of nephrogenic rests, a WT precursor lesion. In WT, YAP1 subcellular localization is dysregulated and p-YAP1 accumulation is a novel biomarker of unfavorable histology. Pediatr Blood Cancer 2014;61:198-205. (c) 2013 Wiley Periodicals, Inc.
C1 [Murphy, Andrew J.; Pierce, Janene; de Caestecker, Christian; Neblett, David; Lovvorn, Harold N., III] Vanderbilt Univ, Sch Med, Dept Pediat Surg, Nashville, TN 37232 USA.
[Libes, Jaime] Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37232 USA.
[de Caestecker, Mark] Vanderbilt Univ, Sch Med, Dept Cell & Dev Biol & Med, Nashville, TN 37232 USA.
[Perantoni, Alan O.; Tanigawa, Shunsuke] NCI, Canc & Dev Biol Lab, Ctr Canc Res, Frederick, MD 21701 USA.
[Anderson, James R.] Childrens Oncol Grp, Dept Biostat, Omaha, NE USA.
[Anderson, James R.] Univ Nebraska Med Ctr, Omaha, NE USA.
[Dome, Jeffrey S.] Childrens Oncol Grp, Div Oncol, Washington, DC USA.
[Dome, Jeffrey S.] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Das, Amrita; Carroll, Thomas J.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
RP Murphy, AJ (reprint author), Vanderbilt Univ, Med Ctr, Dept Pediat Surg, Monroe Carell Jr Childrens Hosp Vanderbilt, 2200 Childrens Way,Doctors Off Tower,Suite 7102, Nashville, TN 37232 USA.
EM andrew.j.murphy@vanderbilt.edu
FU NCI [4R00CA135695-03, 5T32CA 106183-06A1]; Section of Surgical Sciences;
Ingram Cancer Center of the Vanderbilt University Medical Center
FX Grant sponsor: NCI; Grant number: 4R00CA135695-03, 5T32CA 106183-06A1;
Grant sponsor: The Section of Surgical Sciences and the Ingram Cancer
Center of the Vanderbilt University Medical Center
NR 32
TC 9
Z9 9
U1 0
U2 19
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
EI 1545-5017
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD FEB
PY 2014
VL 61
IS 2
BP 198
EP 205
DI 10.1002/pbc.24788
PG 8
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 275RF
UT WOS:000328694300010
PM 24115727
ER
PT J
AU Carol, H
Gorlick, R
Kolb, EA
Morton, CL
Manesh, DM
Keir, ST
Reynolds, CP
Kang, MH
Maris, JM
Wozniak, A
Hickson, I
Lyalin, D
Kurmasheva, RT
Houghton, PJ
Smith, MA
Lock, R
AF Carol, Hernan
Gorlick, Richard
Kolb, E. Anders
Morton, Christopher L.
Manesh, Donya Moradi
Keir, Stephen T.
Reynolds, C. Patrick
Kang, Min H.
Maris, John M.
Wozniak, Amy
Hickson, Ian
Lyalin, Dmitry
Kurmasheva, Raushan T.
Houghton, Peter J.
Smith, Malcolm A.
Lock, Richard
TI Initial Testing (Stage 1) of the Histone Deacetylase Inhibitor,
Quisinostat (JNJ-26481585), by the Pediatric Preclinical Testing Program
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE developmental therapeutics; HDAC inhibitor; preclinical testing
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; T-CELL LYMPHOMA; SOLID TUMORS; IN-VITRO;
PHASE-I; ANTITUMOR-ACTIVITY; GENE-EXPRESSION; HYDROXAMIC ACID; HDAC
INHIBITORS; ACETYLATION
AB BackgroundQuisinostat (JNJ-26481585) is a second-generation pyrimidyl-hydroxamic acid histone deacetylase (HDAC) inhibitor with high cellular potency towards Class I and II HDACs. Quisinostat was selected for clinical development as it showed prolonged pharmacodynamic effects in vivo and demonstrated improved single agent antitumoral efficacy compared to other analogs.
ProceduresQuisinostat was tested against the PPTP in vitro panel at concentrations ranging from 1.0nM to 10M and was tested against the PPTP in vivo panels at a dose of 5mg/kg (solid tumors) or 2.5mg/kg (ALL models) administered intraperitoneally dailyx21.
ResultsIn vitro quisinostat demonstrated potent cytotoxic activity, with T/C% values approaching 0% for all of the cell lines at the highest concentration tested. The median relative IC50 value for the PPTP cell lines was 2.2nM (range <1-19nM). quisinostat induced significant differences in EFS distribution compared to control in 21 of 33 (64%) of the evaluable solid tumor xenografts and in 4 of 8 (50%) of the evaluable ALL xenografts. An objective response was observed in 1 of 33 solid tumor xenografts while for the ALL panel, two xenografts achieved complete response (CR) or maintained CR, and a third ALL xenograft achieved stable disease.
ConclusionsQuisinostat demonstrated broad activity in vitro, and retarded growth in the majority of solid tumor xenografts studied. The most consistent in vivo activity signals observed were for the glioblastoma xenografts and T-cell ALL xenografts. Pediatr Blood Cancer 2014;61:245-252. (c) 2013 Wiley Periodicals, Inc.
C1 [Carol, Hernan; Manesh, Donya Moradi; Lock, Richard] Childrens Canc Inst Australia Med Res, Randwick, NSW, Australia.
[Gorlick, Richard] Childrens Hosp Montefiore, Bronx, NY USA.
[Kolb, E. Anders] Alfred I DuPont Hosp Children, Wilmington, DE USA.
[Morton, Christopher L.; Wozniak, Amy] St Jude Childrens Res Hosp, Memphis, TN 38105 USA.
[Keir, Stephen T.] Duke Univ, Med Ctr, Durham, NC USA.
[Reynolds, C. Patrick; Kang, Min H.] Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA.
[Maris, John M.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA.
[Maris, John M.] Abramson Family Canc Res Inst, Philadelphia, PA USA.
[Hickson, Ian] Janssen Pharmaceut, Antwerp, Belgium.
[Lyalin, Dmitry; Kurmasheva, Raushan T.; Houghton, Peter J.] Nationwide Childrens Hosp, Columbus, OH USA.
[Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Lock, R (reprint author), Univ New S Wales, Lowy Canc Res Ctr, Childrens Canc Inst Australia, Leukaemia Biol Program, Randwick, NSW 2052, Australia.
EM rlock@ccia.unsw.edu.au
RI Houghton, Peter/E-3265-2011; Lock, Richard/G-4253-2013;
OI Hickson, Ian/0000-0002-9167-0514; Reynolds, C.
Patrick/0000-0002-2827-8536
FU National Cancer Institute [NO1-CM-42216, CA21765, CA108786]
FX Grant sponsor: National Cancer Institute; Grant numbers: NO1-CM-42216;
CA21765; CA108786
NR 44
TC 7
Z9 8
U1 1
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
EI 1545-5017
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD FEB
PY 2014
VL 61
IS 2
BP 245
EP 252
DI 10.1002/pbc.24724
PG 8
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 275RF
UT WOS:000328694300018
PM 24038993
ER
PT J
AU Houghton, PJ
Kurmasheva, RT
Kolb, EA
Wu, JR
Gorlick, R
Maris, JM
Smith, MA
AF Houghton, Peter J.
Kurmasheva, Raushan T.
Kolb, E. Anders
Wu, Jianrong
Gorlick, Richard
Maris, John M.
Smith, Malcolm A.
TI Initial Testing (Stage 1) of TAK-701, a Humanized Hepatocyte Growth
Factor Binding Antibody, by the Pediatric Preclinical Testing Program
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE c-Met inhibition; developmental therapeutics; preclinical testing
ID C-MET; EXPRESSION; RECEPTOR; RHABDOMYOSARCOMA; RESISTANCE; MUTATION;
CELLS; MODEL; HGF
AB TAK-701 is a humanized antibody that binds hepatocyte growth factor (HGF), thus suppressing c-Met transduced signaling and c-Met dependent proliferation and migration of tumor cells. Six childhood solid tumor xenografts were selected for evaluating TAK-701 based on immunochemical detection of HGF/c-Met autocrine signaling [i.e., pMet(Tyr1349) and HGF positive]. TAK-701 was tested using a dose of 30mg/kg administered by the intraperitoneal (IP) route twice weekly for 4 weeks. TAK-701 did not induce significant differences in EFS distribution in treated tumors compared to control tumors. Objective responses were not observed in any of the tested solid tumor xenografts. Pediatr Blood Cancer 2014;61:380-382. (c) 2013 Wiley Periodicals, Inc.
C1 [Houghton, Peter J.; Kurmasheva, Raushan T.] Nationwide Childrens Hosp, Columbus, OH 43205 USA.
[Kolb, E. Anders] Alfred I DuPont Hosp Children, Wilmington, DE USA.
[Wu, Jianrong] St Jude Childrens Res Hosp, Memphis, TN 38105 USA.
[Gorlick, Richard] Childrens Hosp Montefiore, Bronx, NY USA.
[Maris, John M.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA.
[Maris, John M.] Abramson Family Canc Res Inst, Philadelphia, PA USA.
[Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Houghton, PJ (reprint author), Nationwide Childrens Hosp, Res Inst, Ctr Childhood Canc, 700 Childrens Dr, Columbus, OH 43205 USA.
EM peter.houghton@nationwidechildrens.org
RI Houghton, Peter/E-3265-2011
FU National Cancer Institute TAK-701 by Millennium Pharmaceuticals
[NO1-CM-42216, CA21765]
FX Grant sponsor: National Cancer Institute TAK-701 was provided by
Millennium Pharmaceuticals; Grant numbers: NO1-CM-42216; CA21765
NR 19
TC 1
Z9 1
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
EI 1545-5017
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD FEB
PY 2014
VL 61
IS 2
BP 380
EP 382
DI 10.1002/pbc.24756
PG 3
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 275RF
UT WOS:000328694300044
PM 24019233
ER
PT J
AU Osinusi, A
Bon, D
Nelson, A
Lee, YJ
Poonia, S
Shivakumar, B
Cai, SY
Wood, B
Haagmans, B
Lempicki, R
Herrmann, E
Sneller, M
Polis, M
Masur, H
Kottilil, S
AF Osinusi, Anu
Bon, Dimitra
Nelson, Amy
Lee, Yu-Jin
Poonia, Seerat
Shivakumar, Bhavana
Cai, Shu Yi
Wood, Brad
Haagmans, Bart
Lempicki, Richard
Herrmann, Eva
Sneller, Michael
Polis, Michael
Masur, Henry
Kottilil, Shyam
TI Comparative Efficacy, Pharmacokinetic, Pharmacodynamic Activity, and
Interferon Stimulated Gene Expression of Different Interferon
Formulations in HIV/HCV Genotype-1 Infected Patients
SO JOURNAL OF MEDICAL VIROLOGY
LA English
DT Article
DE IFN-activity; HCV; HIV; ISGs; pharmacokinetic; pharmacodynamic
ID CHRONIC HEPATITIS-C; HUMAN-IMMUNODEFICIENCY-VIRUS; ALPHA-2A PLUS
RIBAVIRIN; HIV-COINFECTED PERSONS; ANTI-HCV THERAPY; ALBINTERFERON
ALPHA-2B; PEGYLATED INTERFERON; RANDOMIZED-TRIAL; VIRAL KINETICS;
ANTIVIRAL ACTIVITY
AB The effect of different formulations of interferon on therapeutic response in patients coinfected with HIV and HCV is unclear. In this study, the safety, tolerability, viral kinetics (VK) modeling and host responses among HIV/HCV coinfected patients treated with pegylated-IFN or albinterferon alfa-2b (AlbIFN) with weight-based ribavirin were compared. Three trials treated 57 HIV/HCV coinfected genotype-1 patients with PegIFN alfa-2b (1.5 mu g/kg/week) (n=30), PegIFN alfa-2a (180 mu g/week) (n=10), and AlbIFN (900 mu g/q2week) (n=17) in combination with weight-based ribavirin (RBV). HCV RNA, safety labs, and interferon stimulated gene expression (ISG) was evaluated. Adverse events were documented at all study visits. HCV viral kinetics using a full pharmacokinetic/pharmacodynamic model was also evaluated. Baseline patient characteristics were similar across the three studies. All three formulations exhibited comparable safety and tolerability profiles and efficacy. VK/PK/PD parameters for all three studies as measured by mean efficiency and rate of infected cell loss were similar between the three groups. Host responses (ISG expression and immune activation markers) were similar among the three groups. All three regimens induced significant ISG at week 4 (P<0.05) and ISG expression strongly correlated with therapeutic response (r=0.65; P<0.01). In summary, a comprehensive analysis of responses to three different interferon formulations in HIV/HCV coinfected patients demonstrated similar effects. Notably, interferon-based therapy results in a blunted host response followed by modest antiviral effect in HIV/HCV coinfected patients. This suggests that future treatment options that do not rely on host immune responses such as direct antiviral agents would be particularly beneficial in these difficult to treat patients. J. Med. Virol. 86:177-185, 2014. (c) 2013 Wiley Periodicals, Inc.
C1 [Osinusi, Anu; Nelson, Amy; Lee, Yu-Jin; Poonia, Seerat; Shivakumar, Bhavana; Cai, Shu Yi; Sneller, Michael; Polis, Michael; Kottilil, Shyam] NIAID, LIR, NIH, Bethesda, MD 20814 USA.
[Osinusi, Anu; Lempicki, Richard] NCI, Clin Res Directorate, CMRP, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Bon, Dimitra; Herrmann, Eva] Goethe Univ Frankfurt, Dept Med, Inst Biostat & Math Modeling, D-60054 Frankfurt, Germany.
[Wood, Brad] NIH, Div Radiol Radiol & Imaging Sci, Bethesda, MD 20892 USA.
[Haagmans, Bart] Erasmus MC, Rotterdam, Netherlands.
[Masur, Henry] NIH, CCMD, CC, Bethesda, MD 20892 USA.
RP Osinusi, A (reprint author), NIAID, Immunopathogenesis Sect, Immunoregulat Lab, NIH, Bldg10,Rm 6A33-A,10 Ctr Dr, Bethesda, MD 20814 USA.
EM osinusia@niaid.nih.gov
RI Lempicki, Richard/E-1844-2012;
OI Lempicki, Richard/0000-0002-7059-409X; Polis,
Michael/0000-0002-9151-2268
FU NIH (National Institute of Allergy and Infectious Diseases); National
Cancer Institute, National Institutes of Health [HHSN261200800001E]
FX Grant sponsor: Intramural Research Program of the NIH (National
Institute of Allergy and Infectious Diseases); Grant sponsor: National
Cancer Institute, National Institutes of Health; Grant number:
HHSN261200800001E.
NR 33
TC 3
Z9 3
U1 1
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0146-6615
EI 1096-9071
J9 J MED VIROL
JI J. Med. Virol.
PD FEB
PY 2014
VL 86
IS 2
BP 177
EP 185
DI 10.1002/jmv.23773
PG 9
WC Virology
SC Virology
GA 269AR
UT WOS:000328212900001
PM 24166150
ER
PT J
AU Wilson, V
Lefevre, CE
Morton, FB
Brosnan, SF
Paukner, A
Bates, TC
AF Wilson, V.
Lefevre, C. E.
Morton, F. B.
Brosnan, S. F.
Paukner, A.
Bates, T. C.
TI Personality and facial morphology: Links to assertiveness and
neuroticism in capuchins (Sapajus [Cebus] apella)
SO PERSONALITY AND INDIVIDUAL DIFFERENCES
LA English
DT Article
DE Capuchin; Personality; Face morphology; Sapajus; Assertiveness;
Neuroticism; Attentiveness
ID TO-HEIGHT RATIO; SEXUAL-DIMORPHISM; WIDTH; PRIMATES; TESTOSTERONE;
COMPETITION; PERCEPTION; EVOLUTION; BEHAVIOR; HUMANS
AB Personality has important links to health, social status, and life history outcomes (e.g. longevity and reproductive success). Human facial morphology appears to signal aspects of one's personality to others, raising questions about the evolutionary origins of such associations (e.g. signals of mate quality). Studies in non-human primates may help to achieve this goal: for instance, facial width-to-height ratio (fWHR) in the male face has been associated with dominance not only in humans but also in capuchin monkeys. Here we test the association of personality (assertiveness, openness, attentiveness, neuroticism, and sociability) with fWHR, face width/lower-face height, and lower face/face height ratio in 64 capuchins (Sapajus apella). In a structural model of personality and facial metrics, fWHR was associated with assertiveness, while lower face/face height ratio was associated with neuroticism (erratic vs. stable behaviour) and attentiveness (helpfulness vs. distractibility). Facial morphology thus appears to associate with three personality domains, which may act as a signal of status in capuchins. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Wilson, V.; Bates, T. C.] Univ Edinburgh, Dept Psychol, Edinburgh EH8 9YL, Midlothian, Scotland.
[Lefevre, C. E.] Univ York, Dept Psychol, York YO10 5DD, N Yorkshire, England.
[Morton, F. B.] Univ Stirling, Sch Nat Sci, Stirling FK9 4LA, Scotland.
[Brosnan, S. F.] Georgia State Univ, Dept Psychol, Atlanta, GA 30303 USA.
[Brosnan, S. F.] Georgia State Univ, Language Res Ctr, Atlanta, GA 30303 USA.
[Paukner, A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Dept Hlth & Human Serv, Lab Comparat Ethol, Poolesville, MD USA.
[Bates, T. C.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9YL, Midlothian, Scotland.
RP Wilson, V (reprint author), Univ Edinburgh, Dept Psychol, Edinburgh EH8 9YL, Midlothian, Scotland.
EM v.a.d.wilson@sms.ed.ac.uk
OI Bates, Timothy/0000-0002-1153-9007
NR 34
TC 6
Z9 6
U1 2
U2 34
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0191-8869
J9 PERS INDIV DIFFER
JI Pers. Individ. Differ.
PD FEB
PY 2014
VL 58
BP 89
EP 94
DI 10.1016/j.paid.2013.10.008
PG 6
WC Psychology, Social
SC Psychology
GA 269JH
UT WOS:000328237100016
ER
PT J
AU Gillison, ML
Castellsague, X
Chaturvedi, A
Goodman, MT
Snijders, P
Tommasino, M
Arbyn, M
Franceschi, S
AF Gillison, Maura L.
Castellsague, Xavier
Chaturvedi, Anil
Goodman, Marc T.
Snijders, Peter
Tommasino, Massimo
Arbyn, Marc
Franceschi, Silvia
TI Eurogin Roadmap: Comparative epidemiology of HPV infection and
associated cancers of the head and neck and cervix
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Review
DE human papillomavirus; cervical cancer; head and neck cancer;
epidemiology
ID SQUAMOUS-CELL CARCINOMA; HUMAN-PAPILLOMAVIRUS INFECTION; ACTIVE
HUMAN-PAPILLOMAVIRUS; ORAL HUMAN-PAPILLOMAVIRUS; POPULATION-BASED
COHORT; OROPHARYNGEAL CANCER; COLLABORATIVE REANALYSIS; INDIVIDUAL DATA;
CHLAMYDIA-TRACHOMATIS; NATURAL-HISTORY
AB The EUROGIN 2012 roadmap is focused on the comparative epidemiology of human papillomavirus (HPV) associated head and neck squamous cell cancers (HNSCC) and cervical cancers. Discussed are the similarities and differences between the two cancers with regard to global disease burden, HPV prevalence and type distribution, disease cofactors, molecular pathogenesis, treatment approaches, prognostic factors and primary and secondary prevention. The global incidence of HNSCC and cervical cancer is similar; however, a minority of HNSCC in comparison to virtually all cervical cancers is caused by HPV. HPV infection prevalence is considerably lower in the oral than genital regions for reasons that are as yet unclear. Infection at both sites is strongly associated with sexual behavior, but this association does not appear to explain the male predominance of oral HPV infection. Studies of the molecular pathogenesis of HPV-associated HNSCC (predominantly oropharyngeal cancers) are hampered by the lack of a readily detectable intermediate clinical endpoint analogous to cervix intraepithelial neoplasia. Nevertheless, similarities in chromosomal aberrations, gene expression, methylation and microRNA profiles between HPV-positive HNSCC and cervical cancer argue for shared carcinogenic pathways. Treatment approaches to oropharyngeal and cervical cancers are remarkably similar, with the development of HPV-targeted therapies as the ultimate treatment goal. Key research challenges include understanding oral HPV transmission and male predominance, clarifying the role of cofactors, and developing new screening and treatment methods for HPV-associated HNSCC.
C1 [Gillison, Maura L.] Ohio State Univ, Ctr Comprehens Canc, Viral Oncol Program, Columbus, OH 43210 USA.
[Castellsague, Xavier] Inst Catala Oncol IDIBELL, Lhospitalet De Llobregat, Catalonia, Spain.
[Chaturvedi, Anil] Natl Canc Inst, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Goodman, Marc T.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA.
[Snijders, Peter] Vrije Univ Amsterdam Med Ctr, Dept Pathol, Amsterdam, Netherlands.
[Tommasino, Massimo; Franceschi, Silvia] Int Agcy Res Canc, F-69372 Lyon, France.
[Arbyn, Marc] Sci Inst Publ Hlth, Canc Epidemiol Unit, Brussels, Belgium.
[Arbyn, Marc] Univ Antwerp, Antwerp, Belgium.
RP Gillison, ML (reprint author), Ohio State Univ, Ctr Comprehens Canc, Viral Oncol Program, Columbus, OH 43210 USA.
EM maura.gillison@osumc.edu
RI Castellsague Pique, Xavier/N-5795-2014; Chaturvedi, Anil/J-2024-2015
OI Castellsague Pique, Xavier/0000-0002-0802-3595; Chaturvedi,
Anil/0000-0003-2696-8899
FU FP7 research programme of the European Commission (Brussels, Belgium)
FX Grant sponsor: FP7 research programme of the European Commission
(Brussels, Belgium)
NR 108
TC 43
Z9 44
U1 2
U2 37
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 FEB 1
PY 2014
VL 134
IS 3
BP 497
EP 507
DI 10.1002/ijc.28201
PG 11
WC Oncology
SC Oncology
GA 250UG
UT WOS:000326880600001
PM 23568556
ER
PT J
AU Wang-Johanning, F
Li, M
Esteva, FJ
Hess, KR
Yin, BN
Rycaj, K
Plummer, JB
Garza, JG
Ambs, S
Johanning, GL
AF Wang-Johanning, Feng
Li, Ming
Esteva, Francisco J.
Hess, Kenneth R.
Yin, Bingnan
Rycaj, Kiera
Plummer, Joshua B.
Garza, Jeremy G.
Ambs, Stefan
Johanning, Gary L.
TI Human endogenous retrovirus type K antibodies and mRNA as serum
biomarkers of early-stage breast cancer
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE HERV-K; endogenous retroviruses; early detection; biomarkers; breast
cancer; metastasis
ID CARCINOMA IN-SITU; ENVELOPE TRANSCRIPTS; EXPRESSION; THERAPY;
AUTOANTIBODIES; IDENTIFICATION; QUANTITATION; PROTEINS; TUMORS; RISK
AB A simple and accurate test to detect early-stage breast cancer has not been developed. Previous studies indicate that the level of human endogenous retrovirus type K (group HERV-K(HML-2)) transcription may be increased in human breast tumors. We hypothesized that HERV-K(HML-2) reactivation can serve as a biomarker for early detection of breast cancer. Serum samples were collected from women without cancer (controls) and patients with ductal carcinoma in situ (DCIS) and invasive breast cancer. ELISA assays were used to detect serum anti-HERV-K(HML-2) antibody titers. RNA was extracted from sera and analyzed by real-time RT-PCR to quantitate the level of HERV-K(HML-2) mRNA. We measured significantly higher serum mRNA and serum antibody titers against HERV-K(HML-2) proteins in women with DCIS and stage I disease than in women without cancer. At optimized cutoffs for the antibody titers, the assay produced an area under the receiver operating characteristic curve (AUC) of 0.89 (95% confidence interval 0.77-1.00) for DCIS and of 0.95 (95% confidence interval 0.89-1.00) for invasive breast cancer. These AUCs are comparable to those observed for mammograms. We also found that serum HERV-K(HML-2) mRNA tended to be higher in breast cancer patients with a primary tumor who later on developed the metastatic disease than in patients who did not develop cancer metastasis. Our results show that HERV-K(HML-2) antibodies and mRNA are already elevated in the blood at an early stage of breast cancer, and further increase in patients who are at risk of developing a metastatic disease.
What's new? A simple and accurate test to detect early-stage breast cancer does not yet exist. This work suggests that human endogenous retroviruses (HERVs)-remnants of germ line infections that have become part of our genome-are reawakened during the early stages of breast cancer. HERV antibodies and mRNA were thus found to be elevated in the blood at an early stage of breast cancer, and to further increase in patients at risk of developing a metastatic disease. Such sensitive and specific serum assays may usher in a new era of viral biomarkers for detection of early cancer and prediction of cancer metastasis.
C1 [Wang-Johanning, Feng; Li, Ming; Plummer, Joshua B.; Garza, Jeremy G.; Johanning, Gary L.] Univ Texas MD Anderson Canc Ctr, Dept Vet Sci, Houston, TX 77030 USA.
[Wang-Johanning, Feng] Univ Texas MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA.
[Wang-Johanning, Feng; Li, Ming; Plummer, Joshua B.; Johanning, Gary L.] Univ Texas Hlth Sci Ctr Houston, Grad Sch Biomed Sci, Houston, TX 77030 USA.
[Esteva, Francisco J.] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA.
[Hess, Kenneth R.] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA.
[Yin, Bingnan] Methodist Hosp Res Inst, Ctr Inflammat & Epigenet, Houston, TX USA.
[Rycaj, Kiera] Univ Texas MD Anderson Canc Ctr, Dept Mol Carcinogenesis, Houston, TX 77030 USA.
[Ambs, Stefan] NCI, Human Carcinogenesis Lab, Bethesda, MD 20892 USA.
RP Johanning, GL (reprint author), Univ Texas MD Anderson Canc Ctr, 650 Cool Water Dr, Bastrop, TX 78602 USA.
EM gljohann@mdanderson.org
OI Esteva, Francisco/0000-0003-2437-3920
FU Avon Foundation [07-2007-070 01]; Department of Defense
[DAMD1700-1-0123]; Susan G. Komen Breast Cancer Foundation (Susan G.
Komen for the Cure) [BCTR0402892, BCTR000007888]; National Institute of
Environmental Health Sciences Center [ES007784]; Breast Cancer Research
Foundation
FX Grant sponsor: Avon Foundation; Grant number: 07-2007-070 01; Grant
sponsor: Department of Defense; Grant number: DAMD1700-1-0123; Grant
sponsor: Susan G. Komen Breast Cancer Foundation (Susan G. Komen for the
Cure); Grant numbers: BCTR0402892, BCTR000007888; Grant sponsor: The
National Institute of Environmental Health Sciences Center; Grant
number: ES007784; Grant sponsor: The Breast Cancer Research Foundation
NR 32
TC 18
Z9 20
U1 1
U2 26
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 FEB 1
PY 2014
VL 134
IS 3
BP 587
EP 595
DI 10.1002/ijc.28389
PG 9
WC Oncology
SC Oncology
GA 250UG
UT WOS:000326880600009
PM 23873154
ER
PT J
AU Ishikawa, M
Iwamoto, T
Fukumoto, S
Yamada, Y
AF Ishikawa, Masaki
Iwamoto, Tsutomu
Fukumoto, Satoshi
Yamada, Yoshihiko
TI Pannexin 3 Inhibits Proliferation of Osteoprogenitor Cells by Regulating
Wnt and p21 Signaling
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE ATP; Calcium Intracellular Release; Cell Proliferation; Pannexin; Wnt
Signaling; Hemichannel and ER Ca2+Channel; Intracellular ATP and
Ca2+levels; Pannexin 3; Wnt; -Catenin Signaling; p21
ID GAP-JUNCTION PROTEINS; TRANSCRIPTION FACTOR LEF-1; RECEPTOR-RELATED
PROTEIN-5; DUAL-KINASE MECHANISM; BETA-CATENIN; OSTEOBLAST
DIFFERENTIATION; BONE-FORMATION; EXPRESSION; PHOSPHORYLATION; PATHWAY
AB Background: The mechanism of the transition from osteoprogenitor cell proliferation to differentiation is unclear. Results: Panx3 inhibits osteoprogenitor proliferation by blocking canonical Wnt signaling and promoting p21 activation. Conclusion: A Panx3 hemichannel induces multiple Panx3 signaling pathways critical for the cell cycle exit. Significance: Our findings reveal that Panx3 is a new regulator to switch the stage from proliferation to differentiation in osteoprogenitor cells.
Canonical Wnt signaling and BMP promote the proliferation and differentiation of osteoprogenitors, respectively. However, the regulatory mechanism involved in the transition from proliferation to differentiation is unclear. Here, we show that Panx3 (pannexin 3) plays a key role in this transition by inhibiting the proliferation and promoting the cell cycle exit. Using primary calvarial cells and explants, C3H10T1/2 cells, and C2C12 cells, we found that Panx3 expression inhibited cell growth, whereas the inhibition of endogenous Panx3 expression increased it. We also found that the Panx3 hemichannel inhibited cell growth by promoting -catenin degradation through GSK3 activation. Additionally, the Panx3 hemichannel inhibited cyclin D1 transcription and Rb phosphorylation through reduced cAMP/PKA/CREB signaling. Furthermore, the Panx3 endoplasmic reticulum Ca2+ channel induced the transcription and phosphorylation of p21, through the calmodulin/Smad pathway, and resulted in the cell cycle exit. Our results reveal that Panx3 is a new regulator that promotes the switch from proliferation to differentiation of osteoprogenitors via multiple Panx3 signaling pathways.
C1 [Ishikawa, Masaki; Yamada, Yoshihiko] NIDCR, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
[Iwamoto, Tsutomu] Univ Tokushima, Grad Sch, Dept Pediat Dent, Tokushima 7708504, Japan.
[Fukumoto, Satoshi] Tohoku Univ, Grad Sch Dent, Dept Pediat Dent, Sendai, Miyagi 9808576, Japan.
RP Yamada, Y (reprint author), NIDCR, NIH, 30 Convent Dr,MSC 4370,Bldg 30,Rm 407, Bethesda, MD 20892 USA.
EM yoshi.yamada@nih.gov
FU National Institutes of Health Intramural Research Program at the NIDCR;
Ministry of Education, Science, and Culture of Japan [20679006]; NEXT
program [LS010]; Japan Society for the Promotion of Science for Young
Scientists
FX This work was supported, in whole or in part, by National Institutes of
Health Intramural Research Program at the NIDCR. This work was also
supported by Grant-in-Aid 20679006 from the Ministry of Education,
Science, and Culture of Japan (to S. F.) and NEXT program Grant LS010
(to S. F.).; Supported in part by the Research Fellowship of the Japan
Society for the Promotion of Science for Young Scientists.
NR 64
TC 17
Z9 17
U1 0
U2 5
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JAN 31
PY 2014
VL 289
IS 5
BP 2839
EP 2851
DI 10.1074/jbc.M113.523241
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AD6WW
UT WOS:000333403000032
PM 24338011
ER
PT J
AU Scott, I
Webster, BR
Chan, CK
Okonkwo, JU
Han, K
Sack, MN
AF Scott, Iain
Webster, Bradley R.
Chan, Carmen K.
Okonkwo, Joshua U.
Han, Kim
Sack, Michael N.
TI GCN5-like Protein 1 (GCN5L1) Controls Mitochondrial Content through
Coordinated Regulation of Mitochondrial Biogenesis and Mitophagy
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Acetyl Coenzyme A; Autophagy; Lysosomes; Mitochondria; Subcellular
Organelles; GCN5L1; PGC1; Acetylation; Mitophagy
ID SELECTIVE AUTOPHAGY; LIPID-METABOLISM; PARKIN; HOMEOSTASIS; CLEARANCE;
DISEASE
AB Background: The balance between mitochondrial biogenesis and autophagy controls cellular mitochondrial content. Results: Mitochondrial deacetylation-induced mitophagy evokes concurrent and interdependent up-regulation of TFEB and PGC-1 to sustain cellular mitochondrial content. Conclusion: Mitochondrial content is coordinately regulated by the mitochondrial and lysosome biogenesis programs under GCN5L1 control. Significance: Counter-regulatory interdependent programs function to sustain mitochondrial content/homeostasis in a nutrient-sensing, acetylation-dependent manner.
Cellular mitochondrial content is governed by the competing processes of organelle biogenesis and degradation. It is proposed that these programs are tightly regulated to ensure that the cell maintains sufficient organelles to meet its biosynthetic, energetic, and other homeostatic requirements. We recently reported that GCN5L1, a putative nutrient-sensing regulator, controls mitochondrial removal by autophagy. Here we show that genetic deletion of GCN5L1 has a direct positive effect on the expression and activity of Transcriptional Factor EB (TFEB), which acts as a master regulator of autophagy. Surprisingly, the induction of TFEB-mediated autophagy pathways does not diminish cellular mitochondrial content, as its activity is countered by induction of the mitochondrial biogenesis transcriptional co-activator PPAR coactivator 1 (PGC-1). Concurrent induction of the TFEB and PGC-1 pathways results in an increased mitochondrial turnover rate in GCN5L1(-/-) cells. Finally, we show that genetic knockdown of either TFEB or PGC-1 leads to a corresponding decrease in the expression of the other gene, indicating that these proteins act coordinately, and in opposition, to maintain cellular mitochondrial content in response to the modulation of nutrient-sensing signatures.
C1 [Scott, Iain; Webster, Bradley R.; Chan, Carmen K.; Okonkwo, Joshua U.; Han, Kim; Sack, Michael N.] NHLBI, Lab Mitochondrial Biol & Metab, NIH, Bethesda, MD 20892 USA.
RP Sack, MN (reprint author), NHLBI, Bldg 10 CRC,Room 5-3216E,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM sackm@nhlbi.nih.gov
FU NHLBI Intramural Research Program [HL006047-01]
FX This work was funded by the NHLBI Intramural Research Program
(HL006047-01).
NR 27
TC 28
Z9 28
U1 0
U2 5
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JAN 31
PY 2014
VL 289
IS 5
BP 2864
EP 2872
DI 10.1074/jbc.M113.521641
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AD6WW
UT WOS:000333403000034
PM 24356961
ER
PT J
AU Huang, YL
Morales-Rosado, J
Ray, J
Myers, TG
Kho, T
Lu, MF
Munford, RS
AF Huang, Ying-ling
Morales-Rosado, Joel
Ray, Jessica
Myers, Timothy G.
Kho, Terry
Lu, Mingfang
Munford, Robert S.
TI Toll-like Receptor Agonists Promote Prolonged Triglyceride Storage in
Macrophages
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Adipose Triglyceride Lipase; Lipid Droplet; Lipolysis;
Lipopolysaccharide (LPS); Macrophages; Toll-like Receptors (TLR);
Triglyceride; ACSL; DGAT2; Acyl-CoA Synthetase
ID FOAM CELL-FORMATION; COA SYNTHETASE 1; ACYL-COA; LIPID-METABOLISM;
FATTY-ACID; BACTERIAL LIPOPOLYSACCHARIDE; MURINE MACROPHAGES;
KETONE-BODIES; TRIACSIN C; ACCUMULATION
AB Background: How microbial agonists induce macrophages to store triglycerides (TAG) for prolonged periods was not known. Results: Toll-like receptor (TLR)1/2, TLR3, and TLR4 agonists increased fatty acid uptake, increased TAG synthesis, and decreased lipolysis, augmenting TAG storage for 72 h. Conclusion: TAG retention is an active, multifaceted, and long lasting response to sensing microbes. Significance: Prolonged TAG storage contributes to foam cell formation.
Macrophages in infected tissues may sense microbial molecules that significantly alter their metabolism. In a seeming paradox, these critical host defense cells often respond by increasing glucose catabolism while simultaneously storing fatty acids (FA) as triglycerides (TAG) in lipid droplets. We used a load-chase strategy to study the mechanisms that promote long term retention of TAG in murine and human macrophages. Toll-like receptor (TLR)1/2, TLR3, and TLR4 agonists all induced the cells to retain TAG for 3 days. Prolonged TAG retention was accompanied by the following: (a) enhanced FA uptake and FA incorporation into TAG, with long lasting increases in acyl-CoA synthetase long 1 (ACSL1) and diacylglycerol acyltransferase-2 (DGAT2), and (b) decreases in lipolysis and FA -oxidation that paralleled a prolonged drop in adipose triglyceride lipase (ATGL). TLR agonist-induced TAG storage is a multifaceted process that persists long after most early pro-inflammatory responses have subsided and may contribute to the formation of lipid-laden macrophages in infected tissues.
C1 [Huang, Ying-ling; Morales-Rosado, Joel; Ray, Jessica; Kho, Terry; Lu, Mingfang; Munford, Robert S.] NIAID, Antibacterial Host Def Sect, 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 Munford, RS (reprint author), 9000 Rockville Pike,MC3206, Bethesda, MD 20892 USA.
EM robertmunford@gmail.com
FU National Institutes of Health, Division of Intramural Research, NIAID
FX This work was supported, in whole or in part, by National Institutes of
Health, Division of Intramural Research, NIAID.
NR 34
TC 12
Z9 14
U1 0
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JAN 31
PY 2014
VL 289
IS 5
BP 3001
EP 3012
DI 10.1074/jbc.M113.524587
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AD6WW
UT WOS:000333403000047
PM 24337578
ER
PT J
AU Germain, RN
AF Germain, Ronald N.
TI Open questions: A rose is a rose is a rose - or not?
SO BMC BIOLOGY
LA English
DT Editorial Material
ID RNA-SEQ; PROTEIN-LEVELS; EXPRESSION; CELLS; HETEROGENEITY; VARIABILITY;
CONTINUUM; CYTOMETRY; NOISE; GENE
C1 NIAID, NIH, Bethesda, MD 20892 USA.
RP Germain, RN (reprint author), NIAID, NIH, 9000 Rockville Pike,Bldg 4 Rm 126A MSC 0421, Bethesda, MD 20892 USA.
EM rgermain@niaid.nih.gov
FU Intramural NIH HHS
NR 15
TC 2
Z9 2
U1 3
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1741-7007
J9 BMC BIOL
JI BMC Biol.
PD JAN 31
PY 2014
VL 12
AR 2
DI 10.1186/1741-7007-12-2
PG 3
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA AD3HA
UT WOS:000333127700001
PM 24484903
ER
PT J
AU Scheidweiler, KB
Huestis, MA
AF Scheidweiler, Karl B.
Huestis, Marilyn A.
TI Simultaneous quantification of 20 synthetic cannabinoids and 21
metabolites, and semi-quantification of 12 alkyl hydroxy metabolites in
human urine by liquid chromatography-tandem mass spectrometry
SO JOURNAL OF CHROMATOGRAPHY A
LA English
DT Article
DE Synthetic cannabinoids; Urine; Metabolites; Analytical method; LC-MS/MS
ID LC-MS/MS; QUANTITATIVE MEASUREMENT; TOXICOLOGY; JWH-018; DRUGS;
SPECIMENS
AB Clandestine laboratories constantly produce new synthetic cannabinoids to circumvent legislative efforts, complicating toxicological analysis. No extensive synthetic cannabinoid quantitative urinary methods are reported in the literature. We developed and validated a liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for simultaneously quantifying JWH-018, JWH-019, JWH-073, JWH-081, JWH-122, JWH-200, JWH-210, JWH-250, JWH-398, RCS-4, AM-2201, MAM-2201, UR-144, CP 47,497-C7, CP 47,497-C8 and their metabolites, and JWH-203, AM-694, RCS-8, XLR-11 and HU-210 parent compounds in urine. Non-chromatographically resolved alkyl hydroxy metabolite isomers were considered semi-quantitative. beta-Glucuronidase hydrolyzed urine was extracted with 1 ml Biotage SLE+ columns. Specimens were reconstituted in 150 mu L mobile phase consisting of 50% A (0.01% formic acid in water) and 50% 8(0.01% formic acid in 50:50 methanol:acetonitrile). 4 and 25 mu L injections were performed to acquire data in positive and negative ionization modes, respectively. The LC-MS/MS instrument consisted of a Shimadzu UFLCxr system and an ABSciex 5500 Qtrap mass spectrometer with an electrospray source. Gradient chromatographic separation was achieved utilizing a Restek Ultra Biphenyl column with a 0.5 ml/min flow rate and an overall run time of 19.5 and 11.4 mm for positive and negative mode methods, respectively. Quantification was by multiple reaction monitoring with CP 47,497 compounds and HU-210 ionized via negative polarity; all other analytes were acquired in positive mode. Lower and upper limits of linearity were 0.1-1.0 and 50-100 mu g/l (r(2) > 0.994). Validation parameters were evaluated at three concentrations spanning linear dynamic ranges. Inter-day analytical recovery (bias) and imprecision (N = 20) were 88.3-112.2% and 4.3-13.5% coefficient of variation, respectively. Extraction efficiencies and matrix effect (N = 10) were 44-110 and -73 to 52%, respectively. We present a novel LC-MS/MS method for simultaneously quantifying 20 synthetic cannabinoids and 21 metabolites, and semi-quantifying 12 alkyl hydroxy metabolites in urine. Published by Elsevier B.V.
C1 [Scheidweiler, Karl B.; Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Huestis, MA (reprint author), NIDA, IRP, Biomed Res Ctr, NIH, 251 Bayview Blvd,Suite 200,Room 05A-721, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
FU Intramural Research Program of the National Institute on Drug Abuse,
National Institutes of Health
FX The authors would like to recognize Hua-Fen Liu, Xiaohong Chen and
Sumandeep Rana's advice during method development. This research was
supported by the Intramural Research Program of the National Institute
on Drug Abuse, National Institutes of Health.
NR 22
TC 42
Z9 47
U1 6
U2 67
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0021-9673
EI 1873-3778
J9 J CHROMATOGR A
JI J. Chromatogr. A
PD JAN 31
PY 2014
VL 1327
BP 105
EP 117
DI 10.1016/j.chroma.2013.12.067
PG 13
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA AA2FP
UT WOS:000330910800013
PM 24418231
ER
PT J
AU Lipets, E
Vlasova, O
Urnova, E
Margolin, O
Soloveva, A
Ostapushchenko, O
Andersen, J
Ataullakhanov, F
Panteleev, M
AF Lipets, Elena
Vlasova, Olga
Urnova, Evdokiya
Margolin, Oleg
Soloveva, Anna
Ostapushchenko, Olga
Andersen, John
Ataullakhanov, Fazoil
Panteleev, Mikhail
TI Circulating Contact-Pathway-Activating Microparticles Together with
Factors IXa and XIa Induce Spontaneous Clotting in Plasma of Hematology
and Cardiologic Patients
SO PLOS ONE
LA English
DT Article
ID ACTIVE TISSUE FACTOR; ERYTHROCYTE-DERIVED MICROPARTICLES; ISCHEMIC
CEREBROVASCULAR EVENTS; THROMBIN GENERATION; BLOOD-COAGULATION; FACTOR
VIIA; FACTOR XIIA; PROCOAGULANT; PROTEIN; MONOCYTES
AB Background and Objective: Using an in vitro experimental model of immobilized tissue factor-initiated clot growth in platelet-free plasma (thrombodynamics), we observed formation of activator-independent isolated spontaneous clots (SC) throughout the plasma volume in patients with cardiac infarction, acute leukemia, hemolytic anemia, and some other disorders. The aim of this work was to characterize this phenomenon and to identify the mechanisms of SC formation.
Methods and Results: Tissue factor inhibitor (VIIai) prevented SC in only 2 out of 23 patient plasma samples. Specific inhibitors of factors IXa and XIa were efficient in all 8 cases that we tested. Also, only factors IXa and XIa added to normal donors' plasma induced SC formations from isolated centers, in a pattern similar to that in patients' plasma. In contrast, factors VIIa, Va, tissue factor induced uniform plasma clotting. SC disappeared after high-speed centrifugation. However, phospholipid supplementation of centrifuged plasma returned them at least partially in 5 out of 22 patients' plasmas, indicating some other role of microparticles than providing phospholipid surface. Circulating procoagulant microparticles isolated from plasma directly activated factor XII in buffer and in diluted plasma. Flow cytometry revealed an increase in procoagulant microparticles in patients' plasmas with SC.
Conclusion: Our data suggest that combination of circulating active factors (specifically, factors IXa and XIa) with circulating procoagulant and contact-pathway-activating microparticles is the predominant mechanism causing spontaneous clotting in patient plasma.
C1 [Lipets, Elena; Ataullakhanov, Fazoil; Panteleev, Mikhail] Fed Res & Clin Ctr Pediat Hematol Oncol & Immunol, Moscow, Russia.
[Lipets, Elena; Ataullakhanov, Fazoil; Panteleev, Mikhail] HemaCore LLC, Moscow, Russia.
[Vlasova, Olga; Ataullakhanov, Fazoil; Panteleev, Mikhail] Moscow MV Lomonosov State Univ, Moscow, Russia.
[Urnova, Evdokiya; Margolin, Oleg; Soloveva, Anna; Ostapushchenko, Olga; Ataullakhanov, Fazoil; Panteleev, Mikhail] Hlth Minist RF, Natl Res Ctr Hematol, Moscow, Russia.
[Andersen, John] NIAID, Rockville, MD USA.
[Ataullakhanov, Fazoil; Panteleev, Mikhail] Russian Acad Sci, Ctr Theoret Problems Physicochem Pharmacol, Moscow, Russia.
RP Panteleev, M (reprint author), Fed Res & Clin Ctr Pediat Hematol Oncol & Immunol, Moscow, Russia.
EM mapanteleev@yandex.ru
RI Panteleev, Mikhail/H-5491-2012
OI Panteleev, Mikhail/0000-0002-8128-7757
FU HemaCore LLC; Russian Foundation for Basic Research [11-04-00303,
11-04-12080, 12-04-00438, 12-04-33055]; Russian Academy of Sciences
Presidium
FX The study was partially supported by HemaCore LLC, by the Russian
Foundation for Basic Research grants 11-04-00303, 11-04-12080,
12-04-00438, 12-04-33055, and by the Russian Academy of Sciences
Presidium Basic Research Programs 'Molecular and Cellular Biology',
'Basic Science for Medicine', ' Integrative Physiology', and 'Molecular
Mechanisms of Physiologic Functions'. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 29
TC 9
Z9 9
U1 0
U2 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 JAN 31
PY 2014
VL 9
IS 1
AR e87692
DI 10.1371/journal.pone.0087692
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 302RF
UT WOS:000330621900152
PM 24498168
ER
PT J
AU Singleton, AB
AF Singleton, Andrew B.
TI A Unified Process for Neurological Disease
SO SCIENCE
LA English
DT Editorial Material
ID HEREDITARY SPASTIC PARAPLEGIA
C1 NIA, Neurogenet Lab, Bethesda, MD 20892 USA.
RP Singleton, AB (reprint author), NIA, Neurogenet Lab, Bethesda, MD 20892 USA.
EM singleta@mail.nih.gov
RI Singleton, Andrew/C-3010-2009
NR 4
TC 4
Z9 4
U1 0
U2 4
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 JAN 31
PY 2014
VL 343
IS 6170
BP 497
EP 498
DI 10.1126/science.1250172
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 298SC
UT WOS:000330343700033
PM 24482474
ER
PT J
AU Percopo, CM
Dyer, KD
Ochkur, SI
Luo, JL
Fischer, ER
Lee, JJ
Lee, NA
Domachowske, JB
Rosenberg, HF
AF Percopo, Caroline M.
Dyer, Kimberly D.
Ochkur, Sergei I.
Luo, Janice L.
Fischer, Elizabeth R.
Lee, James J.
Lee, Nancy A.
Domachowske, Joseph B.
Rosenberg, Helene F.
TI Activated mouse eosinophils protect against lethal respiratory virus
infection
SO BLOOD
LA English
DT Article
ID MAJOR BASIC-PROTEIN; PNEUMOVIRUS INFECTION; SYNCYTIAL VIRUS; AIRWAY
INFLAMMATION; IN-VIVO; PULMONARY INFLAMMATION; ASPERGILLUS-FUMIGATUS;
PNEUMONIA VIRUS; ANIMAL-MODELS; ASTHMA
AB Eosinophils are recruited to the airways as a prominent feature of the asthmatic inflammatory response where they are broadly perceived as promoting pathophysiology. Respiratory virus infections exacerbate established asthma; however, the role of eosinophils and the nature of their interactions with respiratory viruses remain uncertain. To explore these questions, we established acute infection with the rodent pneumovirus, pneumonia virus of mice (PVM), in 3 distinct mouse models of Th2 cytokine-driven asthmatic inflammation. We found that eosinophils recruited to the airways of otherwise naive mice in response to Aspergillus fumigatus, but not ovalbumin sensitization and challenge, are activated by and degranulate specifically in response to PVM infection. Furthermore, we demonstrate that activated eosinophils from both Aspergillus antigen and cytokine-driven asthma models are profoundly antiviral and promote survival in response to an otherwise lethal PVM infection. Thus, although activated eosinophils within a Th2-polarized inflammatory response may have pathophysiologic features, they are also efficient and effective mediators of antiviral host defense.
C1 [Percopo, Caroline M.; Dyer, Kimberly D.; Luo, Janice L.; Rosenberg, Helene F.] NIAID, IIS, LAD, NIH, Bethesda, MD 20892 USA.
[Ochkur, Sergei I.; Lee, James J.; Lee, Nancy A.] Mayo Clin Arizona, Scottsdale, AZ USA.
[Fischer, Elizabeth R.] NIAID, Res Technol Sect, Rocky Mt Labs, NIH, Hamilton, MT USA.
[Domachowske, Joseph B.] SUNY Upstate Med Univ, Dept Pediat, Syracuse, NY 13210 USA.
RP Rosenberg, HF (reprint author), NIAID, IIS, LAD, NIH, Bldg 10,Room 11C215,MSC-1883,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM hrosenberg@niaid.nih.gov
FU National Institutes of Health, National Institutes of Allergy and
Infectious Diseases, Division of Intramural Research [AI000941,
AI000943]; Mayo Foundation; National Institutes of Health, National
Heart, Lung, and Blood Institute [R01-HL058723, R01-HL065228]; National
Institutes of Health, National Center for Research Resources [RR0109709]
FX This study was supported by National Institutes of Health, National
Institutes of Allergy and Infectious Diseases, Division of Intramural
Research grants AI000941 to AI000943 (H. F. R.); funds from the Mayo
Foundation (N.A.L.); National Institutes of Health, National Heart,
Lung, and Blood Institute grants R01-HL058723 (N.A.L.) and R01-HL065228
(J.J.L.); and a National Institutes of Health, National Center for
Research Resources grant RR0109709 (J.J.L.).
NR 50
TC 17
Z9 17
U1 1
U2 3
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD JAN 30
PY 2014
VL 123
IS 5
BP 743
EP 752
DI 10.1182/blood-2013-05-502443
PG 10
WC Hematology
SC Hematology
GA AH0TE
UT WOS:000335832500027
PM 24297871
ER
PT J
AU Gething, PW
Battle, KE
Bhatt, S
Smith, DL
Eisele, TP
Cibulskis, RE
Hay, SI
AF Gething, Peter W.
Battle, Katherine E.
Bhatt, Samir
Smith, David L.
Eisele, Thomas P.
Cibulskis, Richard E.
Hay, Simon I.
TI Declining malaria in Africa: improving the measurement of progress
SO MALARIA JOURNAL
LA English
DT Review
ID MORTALITY
AB The dramatic escalation of malaria control activities in Africa since the year 2000 has increased the importance of accurate measurements of impact on malaria epidemiology and burden. This study presents a systematic review of the emerging published evidence base on trends in malaria risk in Africa and argues that more systematic, timely, and empirically-based approaches are urgently needed to track the rapidly evolving landscape of transmission.
C1 [Gething, Peter W.; Battle, Katherine E.; Bhatt, Samir; Hay, Simon I.] Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Oxford, England.
[Smith, David L.] Johns Hopkins Bloomberg Sch Publ Hlth, Malaria Res Inst, Baltimore, MD USA.
[Smith, David L.; Hay, Simon I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Eisele, Thomas P.] Tulane Univ, Sch Publ Hlth & Trop Med, Ctr Appl Malaria Res & Evaluat, Dept Global Hlth Syst & Dev, New Orleans, LA USA.
[Cibulskis, Richard E.] World Hlth Org, Global Malaria Programme, Geneva, Switzerland.
RP Gething, PW (reprint author), Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Tinbergen Bldg,South Pk Rd, Oxford, England.
EM peter.gething@zoo.ox.ac.uk
RI Hay, Simon/F-8967-2015; Smith, David/L-8850-2013;
OI Hay, Simon/0000-0002-0611-7272; Smith, David/0000-0003-4367-3849;
Gething, Peter/0000-0001-6759-5449; Battle,
Katherine/0000-0003-2401-2615
FU PWG is a Medical Research Council Career Development Fellow [K00669X];
Bill and Melinda Gates Foundation [OPP1068048]; NIH/NIAID [U19AI089674];
Senior Research Fellowship from the Wellcome Trust [095066]; RAPIDD
program of the Science & Technology Directorate, Department of Homeland
Security; Fogarty International Center, National Institutes of Health;
Malaria Control and Evaluation Partnership in Africa (MACEPA); Bill and
Melinda Gates Foundation
FX We thank Rob Newman for his helpful comments and discussion. We also
thank Kirsten Duda, Ros Howes, Catherine Moyes and David Pigott for
additional comments and proof reading. PWG is a Medical Research Council
Career Development Fellow (K00669X) and receives support from the Bill
and Melinda Gates Foundation (OPP1068048) that also supports BM and SB.
DLS acknowledges funding from NIH/NIAID (U19AI089674). SIH is funded by
a Senior Research Fellowship from the Wellcome Trust (095066) which also
supports KEB. SIH also acknowledges funding support from the RAPIDD
program of the Science & Technology Directorate, Department of Homeland
Security, and the Fogarty International Center, National Institutes of
Health. TPE is funded by the Malaria Control and Evaluation Partnership
in Africa (MACEPA) - a PATH project-through funding from the Bill and
Melinda Gates Foundation. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 22
TC 12
Z9 12
U1 0
U2 13
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 JAN 30
PY 2014
VL 13
AR 39
DI 10.1186/1475-2875-13-39
PG 5
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA AC8GO
UT WOS:000332771700001
PM 24479555
ER
PT J
AU Tarbox, SI
Addington, J
Cadenhead, KS
Cannon, TD
Cornblatt, BA
Perkins, DO
Seidman, LJ
Tsuang, MT
Walker, EF
Heinssen, R
McGlashan, TH
Woods, SW
AF Tarbox, Sarah I.
Addington, Jean
Cadenhead, Kristin S.
Cannon, Tyrone D.
Cornblatt, Barbara A.
Perkins, Diana O.
Seidman, Larry J.
Tsuang, Ming T.
Walker, Elaine F.
Heinssen, Robert
McGlashan, Thomas H.
Woods, Scott W.
TI Functional development in clinical high risk youth: Prediction of
schizophrenia versus other psychotic disorders
SO PSYCHIATRY RESEARCH
LA English
DT Article
DE Adolescence; Diagnosis; Premorbid; Prodrome; Prospective; Psychosis;
Social adjustment
ID 1ST EPISODE PSYCHOSIS; ULTRA-HIGH-RISK; PREMORBID ADJUSTMENT;
SCHIZOAFFECTIVE DISORDER; NEGATIVE SYMPTOMS; ADULT SCHIZOPHRENIA;
PRODROMAL SYMPTOMS; BIPOLAR DISORDER; OBSTETRIC COMPLICATIONS;
INTERRATER RELIABILITY
AB This study evaluates premorbid social and academic functioning in clinical high-risk individuals as predictors of transition to schizophrenia versus another psychotic disorder. Participants were 54 individuals enrolled in phase one of the North American Prodrome Longitudinal Study who over two and a half years of follow-up met criteria for schizophrenia/schizophreniform disorder (n=28) or another psychotic disorder (n=26). Social and academic functioning in childhood, early adolescence, and late adolescence was assessed at baseline using the Cannon-Spoor Premorbid Adjustment Scale. Social maladjustment in late adolescence predicted significantly higher odds of transition to schizophrenia versus another psychotic disorder independent of childhood and early adolescent adjustment (OR = 4.02) and conveyed unique risk over academic maladjustment (O R= 5.64). Premorbid academic maladjustment was not associated with psychotic disorder diagnosis. Results support diagnostic specificity of premorbid social dysfunction to schizophrenia in clinical high-risk youth and underscore an important role for social maladjustment in the developmental pathology of schizophrenia and its prediction. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
C1 [Tarbox, Sarah I.; McGlashan, Thomas H.; Woods, Scott W.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06519 USA.
[Addington, Jean] Univ Calgary, Dept Psychiat, Calgary, AB, Canada.
[Cadenhead, Kristin S.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA.
[Cannon, Tyrone D.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA.
[Cornblatt, Barbara A.] North Shore Long Isl Jewish Hlth Syst, Zucker Hillside Hosp, Psychiat Res, Glen Oaks, NY 11004 USA.
[Cornblatt, Barbara A.] Albert Einstein Coll Med, Dept Psychiat, Bronx, NY 10461 USA.
[Cornblatt, Barbara A.] North Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Manhasset, NY 11030 USA.
[Perkins, Diana O.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA.
[Seidman, Larry J.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Psychiat,Publ Psychiat Div,Massachusetts Men, Boston, MA 02115 USA.
[Seidman, Larry J.] Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, Ctr Behav Genom, La Jolla, CA 92037 USA.
[Tsuang, Ming T.] Harvard Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA.
[Walker, Elaine F.] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA.
[Heinssen, Robert] NIMH, Div Adult Translat Res & Treatment Dev, Bethesda, MD 20892 USA.
RP Tarbox, SI (reprint author), Yale Univ, Sch Med, Dept Psychiat, 34 Pk St,38D, New Haven, CT 06519 USA.
EM sarah.tarbox@yale.edu
FU National Institute of Mental Health [U01 MH066134, R01 MH060720, K24
MH76191, R01 MH065079, R01 MH061523, U01 MH066069, P50 MH064065, R01
MH065562, P50 MH080272, R21 MH075027, R01 MH062066, K05 MH01654, U01
MH066160]; Donaghue Foundation; Eli Lilly and Co
FX This work was supported by National Institute of Mental Health (U01
MH066134 to J.A., R01 MH060720 and K24 MH76191 to K.S.C., R01 MH065079
to T.D.C., R01 MH061523 to B.A.C., U01 MH066069 and P50 MH064065 to
D.O.P, R01 MH065562 and P50 MH080272 to L.J.S., R21 MH075027 to M.T.T,
R01 MH062066 to E.F.W., K05 MH01654 to T.H.M., U01 MH066160 to S.W.W.);
Donaghue Foundation (to S.W.W.); and Eli Lilly and Co (study HGGF to
T.H.M., J.A., D.O.P.).
NR 72
TC 4
Z9 4
U1 4
U2 11
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0165-1781
J9 PSYCHIAT RES
JI Psychiatry Res.
PD JAN 30
PY 2014
VL 215
IS 1
BP 52
EP 60
DI 10.1016/j.psychres.2013.10.006
PG 9
WC Psychiatry
SC Psychiatry
GA AA9LF
UT WOS:000331414300009
PM 24200216
ER
PT J
AU Elsik, CG
Worley, KC
Bennett, AK
Beye, M
Camara, F
Childers, CP
de Graaf, DC
Debyser, G
Deng, JX
Devreese, B
Elhaik, E
Evans, JD
Foster, LJ
Graur, D
Guigo, R
Hoff, KJ
Holder, ME
Hudson, ME
Hunt, GJ
Jiang, HY
Joshi, V
Khetani, RS
Kosarev, P
Kovar, CL
Ma, J
Maleszka, R
Moritz, RFA
Munoz-Torres, MC
Murphy, TD
Muzny, DM
Newsham, IF
Reese, JT
Robertson, HM
Robinson, GE
Rueppell, O
Solovyev, V
Stanke, M
Stolle, E
Tsuruda, JM
Van Vaerenbergh, M
Waterhouse, RM
Weaver, DB
Whitfield, CW
Wu, YQ
Zdobnov, EM
Zhang, L
Zhu, DH
Gibbs, RA
AF Elsik, Christine G.
Worley, Kim C.
Bennett, Anna K.
Beye, Martin
Camara, Francisco
Childers, Christopher P.
de Graaf, Dirk C.
Debyser, Griet
Deng, Jixin
Devreese, Bart
Elhaik, Eran
Evans, Jay D.
Foster, Leonard J.
Graur, Dan
Guigo, Roderic
Hoff, Katharina Jasmin
Holder, Michael E.
Hudson, Matthew E.
Hunt, Greg J.
Jiang, Huaiyang
Joshi, Vandita
Khetani, Radhika S.
Kosarev, Peter
Kovar, Christie L.
Ma, Jian
Maleszka, Ryszard
Moritz, Robin F. A.
Munoz-Torres, Monica C.
Murphy, Terence D.
Muzny, Donna M.
Newsham, Irene F.
Reese, Justin T.
Robertson, Hugh M.
Robinson, Gene E.
Rueppell, Olav
Solovyev, Victor
Stanke, Mario
Stolle, Eckart
Tsuruda, Jennifer M.
Van Vaerenbergh, Matthias
Waterhouse, Robert M.
Weaver, Daniel B.
Whitfield, Charles W.
Wu, Yuanqing
Zdobnov, Evgeny M.
Zhang, Lan
Zhu, Dianhui
Gibbs, Richard A.
CA HGSC Prod Teams
Honey Bee Genome Sequencing Consor
TI Finding the missing honey bee genes: lessons learned from a genome
upgrade
SO BMC GENOMICS
LA English
DT Article
DE Apis mellifera; GC content; Gene annotation; Gene prediction; Genome
assembly; Genome improvement; Genome sequencing; Repetitive DNA;
Transcriptome
ID OPEN READING FRAMES; APIS-MELLIFERA; TRANSPOSABLE ELEMENTS;
CLASSIFICATION-SYSTEM; PROTEIN FAMILIES; DOMAIN DATABASE; TANDEM
REPEATS; DNA-SEQUENCES; SOCIAL INSECT; DRAFT GENOME
AB Background: The first generation of genome sequence assemblies and annotations have had a significant impact upon our understanding of the biology of the sequenced species, the phylogenetic relationships among species, the study of populations within and across species, and have informed the biology of humans. As only a few Metazoan genomes are approaching finished quality (human, mouse, fly and worm), there is room for improvement of most genome assemblies. The honey bee (Apis mellifera) genome, published in 2006, was noted for its bimodal GC content distribution that affected the quality of the assembly in some regions and for fewer genes in the initial gene set (OGSv1.0) compared to what would be expected based on other sequenced insect genomes.
Results: Here, we report an improved honey bee genome assembly (Amel_4.5) with a new gene annotation set (OGSv3.2), and show that the honey bee genome contains a number of genes similar to that of other insect genomes, contrary to what was suggested in OGSv1.0. The new genome assembly is more contiguous and complete and the new gene set includes similar to 5000 more protein-coding genes, 50% more than previously reported. About 1/6 of the additional genes were due to improvements to the assembly, and the remaining were inferred based on new RNAseq and protein data.
Conclusions: Lessons learned from this genome upgrade have important implications for future genome sequencing projects. Furthermore, the improvements significantly enhance genomic resources for the honey bee, a key model for social behavior and essential to global ecology through pollination.
C1 [Elsik, Christine G.] Univ Missouri, Div Anim Sci, Columbia, MO 65211 USA.
[Elsik, Christine G.] Univ Missouri, Div Plant Sci, Columbia, MO 65211 USA.
[Elsik, Christine G.] Univ Missouri, MU Informat Inst, Columbia, MO 65211 USA.
[Elsik, Christine G.; Bennett, Anna K.; Childers, Christopher P.; Munoz-Torres, Monica C.; Reese, Justin T.] Georgetown Univ, Dept Biol, Washington, DC 20057 USA.
[Worley, Kim C.; Deng, Jixin; Holder, Michael E.; Joshi, Vandita; Kovar, Christie L.; Muzny, Donna M.; Newsham, Irene F.; Wu, Yuanqing; Zhang, Lan; Zhu, Dianhui; Gibbs, Richard A.; HGSC Prod Teams] Baylor Coll Med, Human Genome Sequencing Ctr, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Beye, Martin] Univ Dusseldorf, Inst Evolutionary Genet, D-40225 Dusseldorf, Germany.
[Camara, Francisco; Guigo, Roderic] Univ Pompeu Fabra, Ctr Genom Regulat, E-08003 Barcelona, Catalonia, Spain.
[Childers, Christopher P.; Reese, Justin T.] Univ Missouri, Div Anim Sci, Columbia, MO 65211 USA.
[de Graaf, Dirk C.; Van Vaerenbergh, Matthias] Univ Ghent, Lab Zoophysiol, B-9000 Ghent, Belgium.
[Debyser, Griet; Devreese, Bart] Univ Ghent, Lab Prot Biochem & Biomol Engn, B-9000 Ghent, Belgium.
[Elhaik, Eran] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD 21205 USA.
[Evans, Jay D.] USDA ARS, BARC E, Bee Res Lab, Beltsville, MD 20705 USA.
[Foster, Leonard J.] Univ British Columbia, Ctr High Throughput Biol, Dept Biochem & Mol Biol, Vancouver, BC V5Z 1M9, Canada.
[Graur, Dan] Univ Houston, Dept Biol & Biochem, Houston, TX 77204 USA.
[Hoff, Katharina Jasmin; Stanke, Mario] Ernst Moritz Arndt Univ Greifswald, Inst Math & Comp Sci, D-17487 Greifswald, Germany.
[Hudson, Matthew E.] Univ Illinois, Dept Crop Sci, Urbana, IL 61801 USA.
[Hudson, Matthew E.; Ma, Jian] Univ Illinois, Inst Genom Biol, Urbana, IL 61801 USA.
[Hunt, Greg J.] Purdue Univ, Dept Entomol, W Lafayette, IN 47907 USA.
[Jiang, Huaiyang] Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15260 USA.
[Khetani, Radhika S.] Univ Illinois, Roy J Carver Biotechnol Ctr, High Performance Biol Comp HPCBio, Urbana, IL 61801 USA.
[Kosarev, Peter] Softberry Inc, Mt Kisco, NY 10549 USA.
[Ma, Jian] Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA.
[Maleszka, Ryszard] Australian Natl Univ, Res Sch Biol, Canberra, ACT 0200, Australia.
[Moritz, Robin F. A.; Stolle, Eckart] Univ Halle Wittenberg, Inst Zool, D-06099 Halle, Saale, Germany.
[Munoz-Torres, Monica C.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Genom Div, Berkeley, CA 94720 USA.
[Murphy, Terence D.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
[Robertson, Hugh M.] Univ Illinois, Dept Entomol, Urbana, IL 61801 USA.
[Robinson, Gene E.] Univ Illinois, Inst Genom Biol, Dept Entomol, Neurosci Program, Urbana, IL 61801 USA.
[Rueppell, Olav] Univ N Carolina, Dept Biol, Greensboro, NC 27412 USA.
[Solovyev, Victor] King Abdullah Univ Sci & Technol, Comp Elect & Math Sci & Engn Div, Thuwal 239556900, Saudi Arabia.
[Tsuruda, Jennifer M.] Clemson Univ, Clemson, SC 29634 USA.
[Waterhouse, Robert M.; Zdobnov, Evgeny M.] Univ Geneva, CH-1211 Geneva, Switzerland.
[Waterhouse, Robert M.; Zdobnov, Evgeny M.] Swiss Inst Bioinformat, CMU, CH-1211 Geneva, Switzerland.
[Weaver, Daniel B.] Genformatic, Austin, TX 78731 USA.
[Whitfield, Charles W.] Univ Illinois, Dept Entomol, Neurosci Program, Program Ecol & Evolutionary Biol, Urbana, IL 61801 USA.
RP Elsik, CG (reprint author), Univ Missouri, Div Anim Sci, Columbia, MO 65211 USA.
EM elsikc@missouri.edu; kworley@bcm.edu
RI Stolle, Eckart/G-3780-2011; Rueppell, Olav/G-2679-2010; Hudson,
Matthew/A-4438-2008; Evans, Jay/C-8408-2012; Devreese, Bart/B-2011-2009;
Camara Ferreira, Francisco/G-9841-2015; Guigo, Roderic/D-1303-2010;
Waterhouse, Robert/A-1858-2010; Maleszka, Ryszard/A-6078-2008; Zdobnov,
Evgeny/K-1133-2012; Elsik, Christine/C-4120-2017; Moritz,
Robin/K-6053-2012
OI Childers, Anna/0000-0002-0747-8539; Childers, Chris/0000-0002-1253-5550;
Solovyev, Victor/0000-0001-8885-493X; Stolle,
Eckart/0000-0001-7638-4061; Rueppell, Olav/0000-0001-5370-4229; Hudson,
Matthew/0000-0002-4737-0936; Evans, Jay/0000-0002-0036-4651; Devreese,
Bart/0000-0002-9764-2581; Camara Ferreira,
Francisco/0000-0002-1971-5466; Guigo, Roderic/0000-0002-5738-4477;
Waterhouse, Robert/0000-0003-4199-9052; Maleszka,
Ryszard/0000-0003-1855-555X; Elsik, Christine/0000-0002-4248-7713;
Moritz, Robin/0000-0003-0791-887X
FU National Human Genome Research Institute, National Institutes of Health
(NHGRI, NIH) [U54 HG003273]; USDA National Institute of Food Agriculture
[2010-65205-20407]; Clare Luce Booth Fellowship at Georgetown University
FX Funding for the project was provided by a grant to RG from the National
Human Genome Research Institute, National Institutes of Health (NHGRI,
NIH) U54 HG003273. Contributions from members of the CGE lab were
supported by Agriculture and Food Research Initiative Competitive grant
no. 2010-65205-20407 from the USDA National Institute of Food
Agriculture. AKB was supported by a Clare Luce Booth Fellowship at
Georgetown University. The authors are grateful for the HGSC sequence
production teams (Patil, S., Gubbala, S., Aqrawi, P., Arias, F., Bess,
C., Blankenburg, K. B., Brocchini, M., Buhay, C., Challis, D., Chang,
K., Chen, D., Coleman, P., Drummond, J., English, A., Evani, U.,
Francisco, L., Fu, Q., Goodspeed, R., Haessly, T. H., Hale, W., Han, H.,
Holder, M., Hu, Y., Jackson, L., Jakkamsetti, A., Jayaseelan, J. C.,
Kakkar, N., Kalra, D., Kandadi, H., Lee, S., Li, H., Liu, Y., Macmil,
S., Mandapat, C. M., Mata, R., Mathew, T., Matskevitch, T., Munidasa,
M., Nagaswamy, U., Najjar, R., Nguyen, N., Niu, J., Opheim, D.,
Palculict, T., Paul, S., Pellon, M., Perales, L., Pham, C., Pham, P.,
Pu, L.-L., Qi, S., Qu, J., Ren, Y., Ruth, R.T., Saada, N., Sabo, A., San
Lucas, F., Sershen, C., Shafer, J., Shah, N., Shelton, R., Song, X.-Z.,
Tabassum, N., Tang, L., Taylor, A., Taylor, M., Velamala, V., Wan, Z.,
Wang, L., Wang, Y., Warren, J., Weissenberger, G., Wilczek-Boney, K. B.,
Yao, J., Yin, B., Yu, J., Zhang, J., Zhang, L., Zhou, C., Zhu, D., Zhu,
Y., and Zou, X.), and the input of other members of the HGSC genome
assembly team.
NR 108
TC 86
Z9 87
U1 4
U2 73
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 JAN 30
PY 2014
VL 15
AR 86
DI 10.1186/1471-2164-15-86
PG 29
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA AA5DT
UT WOS:000331116900002
PM 24479613
ER
PT J
AU Gordon, LB
Rothman, FG
Lopez-Otin, C
Misteli, T
AF Gordon, Leslie B.
Rothman, Frank G.
Lopez-Otin, Carlos
Misteli, Tom
TI Progeria: A Paradigm for Translational Medicine
SO CELL
LA English
DT Article
ID HUTCHINSON-GILFORD-PROGERIA; DNA-DAMAGE RESPONSES; MUTANT LAMIN-A; MOUSE
MODEL; FARNESYLTRANSFERASE INHIBITOR; DEFECTIVE MATURATION; TELOMERE
DYSFUNCTION; AMELIORATES DISEASE; CELLULAR SENESCENCE; EXTENDS LONGEVITY
AB Rare diseases are powerful windows into biological processes and can serve as models for the development of therapeutic strategies. The progress made on the premature aging disorder Progeria is a shining example of the impact that studies of rare diseases can have.
C1 [Gordon, Leslie B.] Boston Childrens Hosp, Dept Anesthesia, Boston, MA 02115 USA.
[Gordon, Leslie B.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Gordon, Leslie B.] Hasbro Childrens Hosp, Dept Pediat, Providence, RI 02912 USA.
[Gordon, Leslie B.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA.
[Rothman, Frank G.] Brown Univ, Div Biol & Med, Providence, RI 02912 USA.
[Lopez-Otin, Carlos] Univ Oviedo, Inst Univ Oncol IUOPA, Dept Bioquim & Biol Mol, E-33006 Oviedo, Spain.
[Misteli, Tom] NCI, NIH, Bethesda, MD 20892 USA.
RP Gordon, LB (reprint author), Boston Childrens Hosp, Dept Anesthesia, Boston, MA 02115 USA.
EM leslie_gordon@brown.edu; mistelit@mail.nih.gov
RI Lopez-Otin, Carlos/C-6657-2013
OI Lopez-Otin, Carlos/0000-0001-6964-1904
NR 71
TC 49
Z9 49
U1 1
U2 35
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
EI 1097-4172
J9 CELL
JI Cell
PD JAN 30
PY 2014
VL 156
IS 3
BP 400
EP 407
DI 10.1016/j.cell.2013.12.028
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 302DD
UT WOS:000330580800008
PM 24485450
ER
PT J
AU Feuermann, Y
Kang, K
Shamay, A
Robinson, GW
Hennighausen, L
AF Feuermann, Yonatan
Kang, Keunsoo
Shamay, Avi
Robinson, Gertraud W.
Hennighausen, Lothar
TI MiR-21 Is under Control of STAT5 but Is Dispensable for Mammary
Development and Lactation
SO PLOS ONE
LA English
DT Article
ID CELL-PROLIFERATION; GENE-EXPRESSION; RNA-SEQ; MICRORNA-21;
DIFFERENTIATION; EPITHELIUM; TARGETS; GLAND; CANCER; TRANSFORMATION
AB Development of mammary alveolar epithelium during pregnancy is controlled by prolactin, through the transcription factors STAT5A/B that activate specific sets of target genes. Here we asked whether some of STAT5's functions are mediated by microRNAs. The miR-21 promoter sequence contains a bona-fide STAT5 binding site and miR-21 levels increased in HC11 mammary cells upon prolactin treatment. In vivo miR-21 was abundantly expressed in mammary epithelium at day 6 of pregnancy. Analysis of mice lacking miR-21 revealed that their mammary tissue developed normally during pregnancy and dams were able to nurse their pups. Our study demonstrated that although expression of miR-21 is under prolactin control through the transcription factors STAT5A/B its presence is dispensable for mammary development and lactation.
C1 [Feuermann, Yonatan; Kang, Keunsoo; Robinson, Gertraud W.; Hennighausen, Lothar] NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA.
[Shamay, Avi] Minist Agr, Volcani Ctr, Dept Anim Sci, Bet Dagan, Israel.
RP Feuermann, Y (reprint author), NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA.
EM feuermanny@mail.nih.gov
OI Feuermann, Yonatan/0000-0002-6561-6397
FU National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK), NIH
FX This work was funded by the intramural programs of The National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 35
TC 5
Z9 5
U1 1
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JAN 30
PY 2014
VL 9
IS 1
AR e85123
DI 10.1371/journal.pone.0085123
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 302PJ
UT WOS:000330617100006
PM 24497923
ER
PT J
AU Schuemie, MJ
Ryan, PB
DuMouchel, W
Suchard, MA
Madigan, D
AF Schuemie, Martijn J.
Ryan, Patrick B.
DuMouchel, William
Suchard, Marc A.
Madigan, David
TI Interpreting observational studies: why empirical calibration is needed
to correct p-values
SO STATISTICS IN MEDICINE
LA English
DT Article
DE hypothesis testing; calibration; negative controls; observational
studies
ID ORAL BISPHOSPHONATES; LIVER-INJURY; RISK; COHORT; PRESCRIPTION;
VALIDATION; DIAGNOSIS; CANCER; CODES
AB Often the literature makes assertions of medical product effects on the basis of p<0.05'. The underlying premise is that at this threshold, there is only a 5% probability that the observed effect would be seen by chance when in reality there is no effect. In observational studies, much more than in randomized trials, bias and confounding may undermine this premise. To test this premise, we selected three exemplar drug safety studies from literature, representing a case-control, a cohort, and a self-controlled case series design. We attempted to replicate these studies as best we could for the drugs studied in the original articles. Next, we applied the same three designs to sets of negative controls: drugs that are not believed to cause the outcome of interest. We observed how often p<0.05 when the null hypothesis is true, and we fitted distributions to the effect estimates. Using these distributions, we compute calibrated p-values that reflect the probability of observing the effect estimate under the null hypothesis, taking both random and systematic error into account. An automated analysis of scientific literature was performed to evaluate the potential impact of such a calibration. Our experiment provides evidence that the majority of observational studies would declare statistical significance when no effect is present. Empirical calibration was found to reduce spurious results to the desired 5% level. Applying these adjustments to literature suggests that at least 54% of findings with p<0.05 are not actually statistically significant and should be reevaluated. (c) 2013 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.
C1 [Schuemie, Martijn J.] Erasmus MC, Dept Med Informat, Rotterdam, Netherlands.
[Schuemie, Martijn J.; Ryan, Patrick B.; DuMouchel, William; Suchard, Marc A.; Madigan, David] Fdn Natl Inst Hlth, Bethesda, MD USA.
[Ryan, Patrick B.] Janssen Res & Dev LLC, Titusville, NJ USA.
[DuMouchel, William] Oracle Hlth Sci, Burlington, MA USA.
[Suchard, Marc A.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA.
[Madigan, David] Columbia Univ, Dept Stat, New York, NY USA.
RP Schuemie, MJ (reprint author), Erasmus MC, Dept Med Informat, Rotterdam, Netherlands.
EM m.schuemie@erasmusmc.nl
FU Foundation for the National Institutes of Health (FNIH); Abbott, Amgen
Inc.; AstraZeneca; Bayer Healthcare Pharmaceuticals, Inc.; Bristol-Myers
Squibb; Eli Lilly Company; GlaxoSmithKline; Janssen Research and
Development LLC; Lundbeck, Inc.; Merck Co., Inc.; Novartis
Pharmaceuticals Corporation; Pfizer Inc.; Pharmaceutical Research
Manufacturers of America (PhRMA),; Roche; Sanofi; Schering-Plough
Corporation; Takeda; Office of Medical Policy; Center for Drug
Evaluation and Research; US Food and Drug Administration
FX The Observational Medical Outcomes Partnership (OMOP) was funded by the
Foundation for the National Institutes of Health (FNIH) through generous
contributions from the following: Abbott, Amgen Inc., AstraZeneca, Bayer
Healthcare Pharmaceuticals, Inc., Bristol-Myers Squibb, Eli Lilly &
Company, GlaxoSmithKline, Janssen Research and Development LLC,
Lundbeck, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation,
Pfizer Inc., Pharmaceutical Research Manufacturers of America (PhRMA),
Roche, Sanofi, Schering-Plough Corporation, and Takeda. At the time of
publication of this paper, OMOP has been transitioned from FNIH into the
Innovation in Medical Evidence Development and Surveillance (IMEDS)
program at the Reagan-Udall Foundation for the Food and Drug
Administration. Dr. Ryan is an employee of Janssen Research and
Development LLC. Dr. DuMouchel is an employee of Oracle Health Sciences.
Dr. Schuemie received a fellowship from the Office of Medical Policy,
Center for Drug Evaluation and Research, US Food and Drug
Administration, and has become an employee of Janssen Research and
Development LLC since completing the work described here.
NR 22
TC 24
Z9 24
U1 0
U2 14
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 JAN 30
PY 2014
VL 33
IS 2
BP 209
EP 218
DI 10.1002/sim.5925
PG 10
WC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Medicine, Research &
Experimental; Statistics & Probability
SC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Research & Experimental
Medicine; Mathematics
GA 271EJ
UT WOS:000328373800003
PM 23900808
ER
PT J
AU Narouz, MR
Soliman, SE
Fridgen, TD
Nashed, MA
Banoub, JH
AF Narouz, Mina R.
Soliman, Sameh E.
Fridgen, Travis D.
Nashed, Mina A.
Banoub, Joseph H.
TI High-energy collision-induced dissociation tandem mass spectrometry of
regioisomeric lactose palmitic acid monoesters using matrix-assisted
laser desorption/ionization
SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY
LA English
DT Article
ID QUADRUPOLE ION-TRAP; STRUCTURAL-CHARACTERIZATION; SUGAR ESTERS;
FRAGMENTATION; OLIGOSACCHARIDES; SUCROSE; DERIVATIVES; ADDUCTS; SOLVENT;
MS
AB RATIONALEStructural characterization and differentiation of three newly synthesized lactose monopalmitate regioisomers at positions O-3, O-3' and O-6' were realized by single-stage matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry (MALDI-TOF/TOF-MS) in the positive ion mode and by high-energy collision-induced dissociation tandem mass spectrometry (CID-MS/MS).
METHODSA MALDI-TOF/TOF analyzer was utilized for the analysis of these isobaric lactose monopalmitate regioisomers. The CID-MS/MS spectra were acquired using high-energy cid with a 2kV potential difference between the source acceleration voltage and the collision cell.
RESULTSHigh-energy (CID) tandem mass spectrometry (MS/MS) analyses of the sodiated molecules, [M+Na](+), showed distinguishing cross-ring product ions and characteristic fingerprint product ions, which allowed the straight-forward mass spectrometric characterization of these different regiosiomers.
CONCLUSIONSThis investigation allowed us to unravel the novel fragmentation behavior of the sodiated regioisoimer molecules obtained from the mono-substituted D-lactose fatty acid esters using high-energy CID-TOF/TOF-MS/MS analyses. The high-energy CID of the [M+Na](+) ions from the isobaric lactose monopalmitate regioiosmers promoted the formation of characteristic (0,2)A(2) cross-ring cleavage product ions. Copyright (c) 2013 John Wiley & Sons, Ltd.
C1 [Narouz, Mina R.; Fridgen, Travis D.; Banoub, Joseph H.] Mem Univ Newfoundland, Dept Chem, St John, NF A1B 3V6, Canada.
[Narouz, Mina R.] Damanhour Univ, Fac Sci, Dept Chem, Damanhour, Egypt.
[Soliman, Sameh E.; Nashed, Mina A.] Univ Alexandria, Fac Sci, Dept Chem, Alexandria 21321, Egypt.
[Soliman, Sameh E.] NIDDK, LBC, NIH, Bethesda, MD 20892 USA.
[Banoub, Joseph H.] Fisheries & Oceans Canada, Sci Branch, Div Environm Sci, Special Projects, St John, NF A1C 5X1, Canada.
RP Banoub, JH (reprint author), Fisheries & Oceans Canada, Sci Branch, Special Projects, POB 5667, St John, NF A1C 5X1, Canada.
EM banoubjo@dfo-mpo.gc.ca
RI Fridgen, Travis/D-9700-2012
OI Fridgen, Travis/0000-0001-7625-868X
NR 26
TC 1
Z9 1
U1 3
U2 17
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0951-4198
EI 1097-0231
J9 RAPID COMMUN MASS SP
JI Rapid Commun. Mass Spectrom.
PD JAN 30
PY 2014
VL 28
IS 2
BP 169
EP 177
DI 10.1002/rcm.6770
PG 9
WC Biochemical Research Methods; Chemistry, Analytical; Spectroscopy
SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy
GA 269NP
UT WOS:000328248300003
PM 24338964
ER
PT J
AU Zerhouni, EA
AF Zerhouni, Elias A.
TI Turning the Titanic
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Editorial Material
ID LDL CHOLESTEROL; PCSK9
C1 [Zerhouni, Elias A.] Sanofi Rech, Global R&D, F-75008 Paris, France.
[Zerhouni, Elias A.] NIH, Bethesda, MD USA.
RP Zerhouni, EA (reprint author), Sanofi Rech, Global R&D, F-75008 Paris, France.
NR 6
TC 4
Z9 5
U1 0
U2 1
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 JAN 29
PY 2014
VL 6
IS 221
AR 221ed2
DI 10.1126/scitranslmed.3008294
PG 3
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA AA4UA
UT WOS:000331090600001
PM 24476998
ER
PT J
AU Rokic, MB
Stojilkovic, SS
Zemkova, H
AF Rokic, Milos B.
Stojilkovic, Stanko S.
Zemkova, Hana
TI Structural and functional properties of the rat P2X4 purinoreceptor
extracellular vestibule during gating
SO FRONTIERS IN CELLULAR NEUROSCIENCE
LA English
DT Article
DE ATP; cadmium; gate; ion access; lateral portals; purinergic receptors
ID GATED ION CHANNELS; RECEPTOR CHANNELS; P2X(2) RECEPTOR; AGONIST BINDING;
TRANSMEMBRANE DOMAIN; ATP; RESIDUES; PORE; MODULATION; ACCESS
AB P2X receptors are ATP-gated cation channels consisting of three subunits that are mutually intertwined and form an upper, central, and extracellular vestibule with three lateral portals and the channel pore. Here we used cysteine and alanine scanning mutagenesis of the rat P2X4R receptor V47 V61 and K326 N338 sequences to study structural and functional properties of extracellular vestibule during gating. Cysteine mutants were used to test the accessibility of these residue side chains to cadmium during closedopen-desensitized transitions, whereas alanine mutants served as controls. This study revealed the accessibility of residues E51, T57, S59, V61, K326, and M336 to cadmium in channels undergoing a transition from a closed-to-open state and the accessibility of residues V47, G53, D331, 1332, 1333, T335, 1337, and N338 in channels undergoing a transition from an open-to-desensitized state; residues E56 and K329 were accessible during both transitions. The effect of cadmium on channel gating was stimulatory in all reactive V47 V61 mutants and inhibitory in the majority of reactive K326 N338 mutants. The rat P2X4 receptor homology model suggests that residues affected by cadmium in the closed-to-open transition were located within the lumen of the extracellular vestibule and toward the central vestibule; however, the residues affected by cadmium in the open-to-desensitized state were located at the bottom of the vestibule near the pore. Analysis of the model assumed that there is ion access to extracellular and central vestibules through lateral ports when the channel is closed, with residues above the first transmembrane domain being predominantly responsible for ion uptake. Upon receptor activation, there is passage of ions toward the residues located on the upper region of the second transmembrane domain, followed by permeation through the gate region.
C1 [Rokic, Milos B.; Zemkova, Hana] Acad Sci Czech Republic, Inst Physiol, Dept Cellular & Mol Neuroendocrinol, Prague, Czech Republic.
[Rokic, Milos B.; Stojilkovic, Stanko S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Cellular Signaling, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
RP Rokic, MB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Cellular Signaling, Program Dev Neurosci, NIH, 49 Convent Dr, Bethesda, MD 20892 USA.
EM milos.rokic@nih.hhs.gov
RI Zemkova, Hana/C-1844-2012; ROKIC, MILOS/O-7204-2014
OI ROKIC, MILOS/0000-0002-9148-2716
FU Grant Agency of the Czech Republic [P304/12/G069]; Grant Agency of
Charles University [3446/2011]; project "BIOCEV" - Biotechnology and
Biomedicine Centre of the Academy of Sciences; Charles University
[CZ.1.05/1.1.00/02.0109]; Academy of Sciences of the Czech Republic [RVO
67985823]; NICHD, NIH
FX This study was supported by the Grant Agency of the Czech Republic
(P304/12/G069), Grant Agency of Charles University (3446/2011), the
project "BIOCEV" - Biotechnology and Biomedicine Centre of the Academy
of Sciences and Charles University (CZ.1.05/1.1.00/02.0109), the Academy
of Sciences of the Czech Republic (Research Project No. RVO 67985823,
and the Intramural Research Program of the NICHD, NIH.
NR 44
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U1 0
U2 1
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1662-5102
J9 FRONT CELL NEUROSCI
JI Front. Cell. Neurosci.
PD JAN 29
PY 2014
VL 8
AR 3
DI 10.3389/fncel.2014.00003
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA AA4GF
UT WOS:000331053200001
PM 24523669
ER
PT J
AU Alstott, J
Bullmore, ET
Plenz, D
AF Alstott, Jeff
Bullmore, Edward T.
Plenz, Dietmar
TI powerlaw: A Python Package for Analysis of Heavy-Tailed Distributions
SO PLOS ONE
LA English
DT Article
ID NEURONAL AVALANCHES
AB Power laws are theoretically interesting probability distributions that are also frequently used to describe empirical data. In recent years, effective statistical methods for fitting power laws have been developed, but appropriate use of these techniques requires significant programming and statistical insight. In order to greatly decrease the barriers to using good statistical methods for fitting power law distributions, we developed the powerlaw Python package. This software package provides easy commands for basic fitting and statistical analysis of distributions. Notably, it also seeks to support a variety of user needs by being exhaustive in the options available to the user. The source code is publicly available and easily extensible.
C1 [Alstott, Jeff; Plenz, Dietmar] NIMH, Sect Crit Brain Dynam, Bethesda, MD 20892 USA.
[Alstott, Jeff; Bullmore, Edward T.] Univ Cambridge, Behav & Clin Neurosci Inst, Brain Mapping Unit, Cambridge, England.
RP Alstott, J (reprint author), NIMH, Sect Crit Brain Dynam, Bethesda, MD 20892 USA.
EM alstottjd@mail.nih.gov
OI Bullmore, Edward/0000-0002-8955-8283
FU National Institute of MentalHealth; Wellcome Trust; Medical Research
Council (UK); National Institutes of Health-Oxford-Cambridge Scholarship
Program; GlaxoSmithKline (GSK)
FX This research was supported by the Intramural Research Program of the
National Institute of MentalHealth. The Behavioural and Clinical
Neuroscience Institute, University of Cambridge, is supported by the
Wellcome Trust and the Medical Research Council (UK). J.A. is supported
by the National Institutes of Health-Oxford-Cambridge Scholarship
Program. E. B. is employed half-time by the University of Cambridge, UK,
and half-time by GlaxoSmithKline (GSK). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript. The authors would also like to declare
one of the authors, Ed Bullmore, is employed half-time by
GlaxoSmithKline (GSK), a commercial funder. This does not alter their
adherence to all the PLOS ONE policies on sharing data and materials.
NR 14
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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 JAN 29
PY 2014
VL 9
IS 1
AR e85777
DI 10.1371/journal.pone.0085777
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 301ZC
UT WOS:000330570000016
PM 24489671
ER
PT J
AU Chandrasekaran, P
Moore, V
Buckley, M
Spurrier, J
Kehrl, JH
Venkatesan, S
AF Chandrasekaran, Prabha
Moore, Victoria
Buckley, Monica
Spurrier, Joshua
Kehrl, John H.
Venkatesan, Sundararajan
TI HIV-1 Nef Down-Modulates C-C and C-X-C Chemokine Receptors via Ubiquitin
and Ubiquitin-Independent Mechanism
SO PLOS ONE
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; PROTEIN-COUPLED RECEPTORS; CELL-SURFACE
EXPRESSION; REGULATES MHC-I; TYPE-1 NEF; ENDOCYTIC PATHWAY; WW DOMAINS;
MEMBRANE TRAFFICKING; ARRESTIN-2 INTERACTS; PERIPHERAL-TISSUES
AB Human and Simian Immunodeficiency virus (HIV-1, HIV-2, and SIV) encode an accessory protein, Nef, which is a pathogenesis and virulence factor. Nef is a multivalent adapter that dysregulates the trafficking of many immune cell receptors, including chemokine receptors (CKRs). Physiological endocytic itinerary of agonist occupied CXCR4 involves ubiquitinylation of the phosphorylated receptor at three critical lysine residues and dynamin-dependent trafficking through the ESCRT pathway into lysosomes for degradation. Likewise, Nef induced CXCR4 degradation was critically dependent on the three lysines in the C-terminal -SSLKILSKGK-motif. Nef directly recruits the HECT domain E3 ligases AIP4 or NEDD4 to CXCR4 in the resting state. This mechanism was confirmed by ternary interactions of Nef, CXCR4 and AIP4 or NEDD4; by reversal of Nef effect by expression of catalytically inactive AIP4-C830A mutant; and siRNA knockdown of AIP4, NEDD4 or some ESCRT-0 adapters. However, ubiquitinylation dependent lysosomal degradation was not the only mechanism by which Nef downregulated CKRs. Agonist and Nef mediated CXCR2 (and CXCR1) degradation was ubiquitinylation independent. Nef also profoundly downregulated the naturally truncated CXCR4 associated with WHIM syndrome and engineered variants of CXCR4 that resist CXCL12 induced internalization via an ubiquitinylation independent mechanism.
C1 [Chandrasekaran, Prabha; Moore, Victoria; Buckley, Monica; Spurrier, Joshua; Venkatesan, Sundararajan] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Kehrl, John H.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
RP Venkatesan, S (reprint author), NIAID, Lab Mol Immunol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM sv1s@nih.gov
OI Kehrl, John/0000-0002-6526-159X
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX This research was funded by the Intramural Research Program of 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.
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PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JAN 29
PY 2014
VL 9
IS 1
AR e86998
DI 10.1371/journal.pone.0086998
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 301ZC
UT WOS:000330570000090
PM 24489825
ER
PT J
AU Finkle, WD
Greenland, S
Ridgeway, GK
Adams, JL
Frasco, MA
Cook, MB
Fraumeni, JF
Hoover, RN
AF Finkle, William D.
Greenland, Sander
Ridgeway, Gregory K.
Adams, John L.
Frasco, Melissa A.
Cook, Michael B.
Fraumeni, Joseph F., Jr.
Hoover, Robert N.
TI Increased Risk of Non-Fatal Myocardial Infarction Following Testosterone
Therapy Prescription in Men
SO PLOS ONE
LA English
DT Article
ID CORONARY-HEART-DISEASE; OLDER MEN; CARDIOVASCULAR EVENTS;
HORMONE-THERAPY; METAANALYSIS; THROMBOSIS; AUTOPSY; BLOOD
AB Background: An association between testosterone therapy (TT) and cardiovascular disease has been reported and TT use is increasing rapidly.
Methods: We conducted a cohort study of the risk of acute non-fatal myocardial infarction (MI) following an initial TT prescription (N = 55,593) in a large health-care database. We compared the incidence rate of MI in the 90 days following the initial prescription (post-prescription interval) with the rate in the one year prior to the initial prescription (pre-prescription interval) (post/pre). We also compared post/pre rates in a cohort of men prescribed phosphodiesterase type 5 inhibitors (PDE5I; sildenafil or tadalafil, N = 167,279), and compared TT prescription post/pre rates with the PDE5I post/pre rates, adjusting for potential confounders using doubly robust estimation.
Results: In all subjects, the post/pre-prescription rate ratio (RR) for TT prescription was 1.36 (1.03, 1.81). In men aged 65 years and older, the RR was 2.19 (1.27, 3.77) for TT prescription and 1.15 (0.83, 1.59) for PDE5I, and the ratio of the rate ratios (RRR) for TT prescription relative to PDE5I was 1.90 (1.04, 3.49). The RR for TT prescription increased with age from 0.95 (0.54, 1.67) for men under age 55 years to 3.43 (1.54, 7.56) for those aged >= 75 years (p(trend) = 0.03), while no trend was seen for PDE5I (p(trend) = 0.18). In men under age 65 years, excess risk was confined to those with a prior history of heart disease, with RRs of 2.90 (1.49, 5.62) for TT prescription and 1.40 (0.91, 2.14) for PDE5I, and a RRR of 2.07 (1.05, 4.11).
Discussion: In older men, and in younger men with pre-existing diagnosed heart disease, the risk of MI following initiation of TT prescription is substantially increased.
C1 [Finkle, William D.; Ridgeway, Gregory K.; Adams, John L.; Frasco, Melissa A.] Consolidated Res Inc, Los Angeles, CA 90045 USA.
[Greenland, Sander] Univ Calif Los Angeles, Dept Epidemiol, Los Angeles, CA USA.
[Greenland, Sander] Univ Calif Los Angeles, Dept Stat, Los Angeles, CA USA.
[Cook, Michael B.; Fraumeni, Joseph F., Jr.; Hoover, Robert N.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Finkle, WD (reprint author), Consolidated Res Inc, Los Angeles, CA 90045 USA.
EM bill@consolidated-research.com; hooverr@mail.nih.gov
RI Cook, Michael/A-5641-2009;
OI Cook, Michael/0000-0002-0533-7302; Ridgeway, Greg/0000-0001-6911-0804
FU National Cancer Institute
FX This study was supported by the Intramural Research Program of the
National Cancer Institute. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
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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 JAN 29
PY 2014
VL 9
IS 1
AR e85805
DI 10.1371/journal.pone.0085805
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 301ZC
UT WOS:000330570000017
PM 24489673
ER
PT J
AU Little, MP
Kukush, AG
Masiuk, SV
Shklyar, S
Carroll, RJ
Lubin, JH
Kwon, D
Brenner, AV
Tronko, MD
Mabuchi, K
Bogdanova, TI
Hatch, M
Zablotska, LB
Tereshchenko, VP
Ostroumova, E
Bouville, AC
Drozdovitch, V
Chepurny, MI
Kovgan, LN
Simon, SL
Shpak, VM
Likhtarev, IA
AF Little, Mark P.
Kukush, Alexander G.
Masiuk, Sergii V.
Shklyar, Sergiy
Carroll, Raymond J.
Lubin, Jay H.
Kwon, Deukwoo
Brenner, Alina V.
Tronko, Mykola D.
Mabuchi, Kiyohiko
Bogdanova, Tetiana I.
Hatch, Maureen
Zablotska, Lydia B.
Tereshchenko, Valeriy P.
Ostroumova, Evgenia
Bouville, Andre C.
Drozdovitch, Vladimir
Chepurny, Mykola I.
Kovgan, Lina N.
Simon, Steven L.
Shpak, Victor M.
Likhtarev, Ilya A.
TI Impact of Uncertainties in Exposure Assessment on Estimates of Thyroid
Cancer Risk among Ukrainian Children and Adolescents Exposed from the
Chernobyl Accident
SO PLOS ONE
LA English
DT Article
ID ATOMIC-BOMB SURVIVORS; CONDITIONAL-INDEPENDENCE MODELS; MEASUREMENT
ERROR PROBLEMS; MORTALITY DOSE-RESPONSE; REGRESSION CALIBRATION;
CERVICAL-CANCER; RADIATION; CURVATURE; I-131; EPIDEMIOLOGY
AB The 1986 accident at the Chernobyl nuclear power plant remains the most serious nuclear accident in history, and excess thyroid cancers, particularly among those exposed to releases of iodine-131 remain the best-documented sequelae. Failure to take dose-measurement error into account can lead to bias in assessments of dose-response slope. Although risks in the Ukrainian-US thyroid screening study have been previously evaluated, errors in dose assessments have not been addressed hitherto. Dose-response patterns were examined in a thyroid screening prevalence cohort of 13,127 persons aged <18 at the time of the accident who were resident in the most radioactively contaminated regions of Ukraine. We extended earlier analyses in this cohort by adjusting for dose error in the recently developed TD-10 dosimetry. Three methods of statistical correction, via two types of regression calibration, and Monte Carlo maximum-likelihood, were applied to the doses that can be derived from the ratio of thyroid activity to thyroid mass. The two components that make up this ratio have different types of error, Berkson error for thyroid mass and classical error for thyroid activity. The first regression-calibration method yielded estimates of excess odds ratio of 5.78 Gy(-1) (95% CI 1.92, 27.04), about 7% higher than estimates unadjusted for dose error. The second regression-calibration method gave an excess odds ratio of 4.78 Gy(-1) (95% CI 1.64, 19.69), about 11% lower than unadjusted analysis. The Monte Carlo maximum-likelihood method produced an excess odds ratio of 4.93 Gy(-1) (95% CI 1.67, 19.90), about 8% lower than unadjusted analysis. There are borderline-significant (p=0.101-0.112) indications of downward curvature in the dose response, allowing for which nearly doubled the low-dose linear coefficient. In conclusion, dose-error adjustment has comparatively modest effects on regression parameters, a consequence of the relatively small errors, of a mixture of Berkson and classical form, associated with thyroid dose assessment.
C1 [Little, Mark P.; Kwon, Deukwoo; Brenner, Alina V.; Mabuchi, Kiyohiko; Hatch, Maureen; Ostroumova, Evgenia; Bouville, Andre C.; Drozdovitch, Vladimir; Simon, Steven L.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,US Dept HHS, Bethesda, MD 20892 USA.
[Kukush, Alexander G.; Masiuk, Sergii V.; Shklyar, Sergiy; Chepurny, Mykola I.; Kovgan, Lina N.; Likhtarev, Ilya A.] Ukrainian Radiat Protect Inst, Kiev, Ukraine.
[Kukush, Alexander G.; Shklyar, Sergiy] Taras Shevchenko Natl Univ Kyiv, Kiev, Ukraine.
[Carroll, Raymond J.] Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA.
[Lubin, Jay H.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,US Dept HHS, Bethesda, MD 20892 USA.
[Kwon, Deukwoo] Univ Miami, Sylvester Comprehens Canc Ctr, Miami, FL USA.
[Tronko, Mykola D.; Bogdanova, Tetiana I.; Tereshchenko, Valeriy P.; Shpak, Victor M.] Ukraine Acad Med Sci, State Inst Inst Endocrinol & Metab, Kiev, Ukraine.
[Zablotska, Lydia B.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
RP Little, MP (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,US Dept HHS, Bethesda, MD 20892 USA.
EM mark.little@nih.gov
OI Little, Mark/0000-0003-0980-7567
FU National Institutes of Health, the National Cancer Institute, Division
of Cancer Epidemiology and Genetics; National Cancer Institute
[R37-CA057030]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, the National Cancer Institute, Division
of Cancer Epidemiology and Genetics. Professor RJC's research was
supported by a grant from the National Cancer Institute (R37-CA057030).
The National Cancer Institute approved the present paper for
publication. The funders (NIH) had no other role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 55
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U1 2
U2 14
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 JAN 29
PY 2014
VL 9
IS 1
AR e85723
DI 10.1371/journal.pone.0085723
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 301ZC
UT WOS:000330570000014
PM 24489667
ER
PT J
AU Myles, IA
Pincus, NB
Fontecilla, NM
Datta, SK
AF Myles, Ian A.
Pincus, Nathan B.
Fontecilla, Natalia M.
Datta, Sandip K.
TI Effects of Parental Omega-3 Fatty Acid Intake on Offspring Microbiome
and Immunity
SO PLOS ONE
LA English
DT Article
ID POLYUNSATURATED FATTY-ACIDS; REGULATORY T-CELLS; GUT MICROBIOTA; N-3;
INFLAMMATION; EXPRESSION; RESOLVIN; DIFFERS; MODEL; VITRO
AB The "Western diet" is characterized by increased intake of saturated and omega-6 (n-6) fatty acids with a relative reduction in omega-3 (n-3) consumption. These fatty acids can directly and indirectly modulate the gut microbiome, resulting in altered host immunity. Omega-3 fatty acids can also directly modulate immunity through alterations in the phospholipid membranes of immune cells, inhibition of n-6 induced inflammation, down-regulation of inflammatory transcription factors, and by serving as pre-cursors to anti-inflammatory lipid mediators such as resolvins and protectins. We have previously shown that consumption by breeder mice of diets high in saturated and n-6 fatty acids have inflammatory and immune-modulating effects on offspring that are at least partially driven by vertical transmission of altered gut microbiota. To determine if parental diets high in n-3 fatty acids could also affect offspring microbiome and immunity, we fed breeding mice an n-3-rich diet with 40% calories from fat and measured immune outcomes in their offspring. We found offspring from mice fed diets high in n-3 had altered gut microbiomes and modestly enhanced anti-inflammatory IL-10 from both colonic and splenic tissue. Omega-3 pups were protected during peanut oral allergy challenge with small but measurable alterations in peanut-related serologies. However, n-3 pups displayed a tendency toward worsened responses during E. coli sepsis and had significantly worse outcomes during Staphylococcus aureus skin infection. Our results indicate excess parental n-3 fatty acid intake alters microbiome and immune response in offspring.
C1 [Myles, Ian A.; Pincus, Nathan B.; Fontecilla, Natalia M.; Datta, Sandip K.] NIAID, Bacterial Pathogenesis Unit, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Myles, IA (reprint author), NIAID, Bacterial Pathogenesis Unit, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM mylesi@niaid.nih.gov
OI Datta, Sandip/0000-0003-0243-7815
FU National Institutes of Health; Office of Dietary Supplements
FX The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript. Also the funding
was entirely from National Institutes of Health and the Office of
Dietary Supplements. There are no current external funding sources for
this study.
NR 37
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U1 6
U2 43
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 JAN 29
PY 2014
VL 9
IS 1
AR e87181
DI 10.1371/journal.pone.0087181
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 301ZC
UT WOS:000330570000114
PM 24489864
ER
PT J
AU Shive, HR
West, RR
Embree, LJ
Golden, CD
Hickstein, DD
AF Shive, Heather R.
West, Robert R.
Embree, Lisa J.
Golden, Champa D.
Hickstein, Dennis D.
TI brca2 and tp53 Collaborate in Tumorigenesis in Zebrafish
SO PLOS ONE
LA English
DT Article
ID BREAST-CANCER; GENETIC-HETEROGENEITY; MUTATOR PHENOTYPE; OVARIAN-CANCER;
TUMOR TYPES; MUTATIONS; P53
AB Germline mutations in the tumor suppressor genes BRCA2 and TP53 significantly influence human cancer risk, and cancers from humans who inherit one mutant allele for BRCA2 or TP53 often display loss of the wildtype allele. In addition, BRCA2-associated cancers often exhibit mutations in TP53. To determine the relationship between germline heterozygous mutation (haploinsufficiency) and somatic loss of heterozygosity (LOH) for BRCA2 and TP53 in carcinogenesis, we analyzed zebrafish with heritable mutations in these two genes. Tumor-bearing zebrafish were examined by histology, and normal and neoplastic tissues were collected by laser-capture microdissection for LOH analyses. Zebrafish on a heterozygous tp53(M214K) background had a high incidence of malignant tumors. The brca2(Q658X) mutation status determined both the incidence of LOH and the malignant tumor phenotype. LOH for tp53 occurred in the majority of malignant tumors from brca2 wildtype and heterozygous mutant zebrafish, and most of these were malignant peripheral nerve sheath tumors. Malignant tumors in zebrafish with heterozygous mutations in both brca2 and tp53 frequently displayed LOH for both genes. In contrast, LOH for tp53 was uncommon in malignant tumors from brca2 homozygotes, and these tumors were primarily undifferentiated sarcomas. Thus, carcinogenesis in zebrafish with combined mutations in tp53 and brca2 typically requires biallelic mutation or loss of at least one of these genes, and the specific combination of inherited mutations influences the development of LOH and the tumor phenotype. These results provide insight into cancer development associated with heritable BRCA2 and TP53 mutations.
C1 [Shive, Heather R.; West, Robert R.; Embree, Lisa J.; Golden, Champa D.; Hickstein, Dennis D.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Shive, HR (reprint author), NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM shiveh@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health (NIH),
National Cancer Institute, Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
National Institutes of Health (NIH), National Cancer Institute, Center
for Cancer Research. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 27
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U1 2
U2 13
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 JAN 29
PY 2014
VL 9
IS 1
AR e87177
DI 10.1371/journal.pone.0087177
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 301ZC
UT WOS:000330570000113
PM 24489863
ER
PT J
AU Wang, YP
Nie, JX
Yap, PT
Li, G
Shi, F
Geng, XJ
Guo, L
Shen, DG
AF Wang, Yaping
Nie, Jingxin
Yap, Pew-Thian
Li, Gang
Shi, Feng
Geng, Xiujuan
Guo, Lei
Shen, Dinggang
CA Alzheimers Dis Neuroimaging Initia
TI Knowledge-Guided Robust MRI Brain Extraction for Diverse Large-Scale
Neuroimaging Studies on Humans and Non-Human Primates
SO PLOS ONE
LA English
DT Article
ID SKULL STRIPPING PROBLEM; ALZHEIMERS-DISEASE; AUTOMATIC SEGMENTATION;
GRAY-MATTER; IMAGES; CLASSIFICATION; REGISTRATION; ALGORITHM; VOLUMES;
CORTEX
AB Accurate and robust brain extraction is a critical step in most neuroimaging analysis pipelines. In particular, for the large-scale multi-site neuroimaging studies involving a significant number of subjects with diverse age and diagnostic groups, accurate and robust extraction of the brain automatically and consistently is highly desirable. In this paper, we introduce population-specific probability maps to guide the brain extraction of diverse subject groups, including both healthy and diseased adult human populations, both developing and aging human populations, as well as non-human primates. Specifically, the proposed method combines an atlas-based approach, for coarse skull-stripping, with a deformable-surface-based approach that is guided by local intensity information and population-specific prior information learned from a set of real brain images for more localized refinement. Comprehensive quantitative evaluations were performed on the diverse large-scale populations of ADNI dataset with over 800 subjects (55 similar to 90 years of age, multi-site, various diagnosis groups), OASIS dataset with over 400 subjects (18 similar to 96 years of age, wide age range, various diagnosis groups), and NIH pediatrics dataset with 150 subjects (5 similar to 18 years of age, multi-site, wide age range as a complementary age group to the adult dataset). The results demonstrate that our method consistently yields the best overall results across almost the entire human life span, with only a single set of parameters. To demonstrate its capability to work on non-human primates, the proposed method is further evaluated using a rhesus macaque dataset with 20 subjects. Quantitative comparisons with popularly used state-of-the-art methods, including BET, Two-pass BET, BET-B, BSE, HWA, ROBEX and AFNI, demonstrate that the proposed method performs favorably with superior performance on all testing datasets, indicating its robustness and effectiveness.
C1 [Wang, Yaping; Guo, Lei] Northwestern Polytech Univ, Sch Automat, Xian 710072, Shaanxi Provinc, Peoples R China.
[Wang, Yaping; Nie, Jingxin; Yap, Pew-Thian; Li, Gang; Shi, Feng; Shen, Dinggang] Univ N Carolina, Dept Radiol, Chapel Hill, NC 27515 USA.
[Wang, Yaping; Nie, Jingxin; Yap, Pew-Thian; Li, Gang; Shi, Feng; Shen, Dinggang] Univ N Carolina, BRIC, Chapel Hill, NC USA.
[Geng, Xiujuan] NIDA, Neuroimaging Res Branch, Baltimore, MD USA.
[Shen, Dinggang] Korea Univ, Dept Brain & Cognit Engn, Seoul, South Korea.
RP Shen, DG (reprint author), Univ N Carolina, Dept Radiol, Chapel Hill, NC 27515 USA.
EM dgshen@med.unc.edu
RI Li, Gang /D-3324-2013
FU NIH [EB008374, EB006733, EB009634, AG041721, MH100217, AG042599];
National Natural Science Foundation of China [61273362, 61333017];
National Research Foundation grant of Korea [2012-005741]; Alzheimer's
Disease Neuroimaging Initiative (ADNI) (National Institutes of Health
Grant) [U01 AG024904]
FX This work was supported in part by NIH grants EB008374, EB006733,
EB009634, AG041721, MH100217, AG042599, National Natural Science
Foundation of China (No. 61273362, No. 61333017), and National Research
Foundation grant of Korea (No. 2012-005741). The University of North
Carolina at Chapel Hill's Libraries provided support for open access
publication. ADNI data collection and sharing for this project was
supported by the Alzheimer's Disease Neuroimaging Initiative (ADNI)
(National Institutes of Health Grant U01 AG024904), P30 AG010129, K01
AG030514, the Dana Foundation. OASIS data collection and sharing for
this project was supported by P50 AG05681, P01 AG03991, R01 AG021910,
P50 MH071616, U24 RR021382, R01 MH56584. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 49
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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 JAN 29
PY 2014
VL 9
IS 1
AR e77810
DI 10.1371/journal.pone.0077810
PG 23
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 301ZC
UT WOS:000330570000002
PM 24489639
ER
PT J
AU Lippincott-Schwartz, J
Sengupta, P
Chen, A
van Engelenburg, S
AF Lippincott-Schwartz, Jennifer
Sengupta, Prabuddha
Chen, Antony
van Engelenburg, Schuyler
TI Nanoscale Mechanisms Underlying HIV-1 Viral Particle Assembly and
Release
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Lippincott-Schwartz, Jennifer; Sengupta, Prabuddha; Chen, Antony; van Engelenburg, Schuyler] NICHD, NIH, Bethesda, MD USA.
NR 0
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PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
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SU 1
BP 5A
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SC Biophysics
GA AI6QE
UT WOS:000337000400028
ER
PT J
AU Birkenfeld, AL
Samuel, VT
Shulman, GI
De Cabo, R
Reenan, RA
Zhu, CT
Helfand, S
AF Birkenfeld, Andreas L.
Samuel, Varman T.
Shulman, Gerald I.
De Cabo, Rafael
Reenan, Robert A.
Zhu, Chen-Tseh
Helfand, Stephen
TI I'm not Dead Yet: Flies and Mice
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Birkenfeld, Andreas L.] Ctr Cardiovasc Res, Berlin, Germany.
[Samuel, Varman T.; Shulman, Gerald I.] Yale Univ, Sch Med, New Haven, CT USA.
[De Cabo, Rafael] NIA, Baltimore, MD 21224 USA.
[Reenan, Robert A.; Zhu, Chen-Tseh; Helfand, Stephen] Brown Univ, Providence, RI 02912 USA.
RI Zhu, Chen-Tseh (Lei)/A-9761-2014
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PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
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BP 12A
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GA AI6QE
UT WOS:000337000400061
ER
PT J
AU Fischer, AR
Elliot, H
Waterman, C
Danuser, G
AF Fischer, A. R.
Elliot, Hunter
Waterman, Clare
Danuser, Gaudenz
TI Myosin II Controls Cellular Branching Morphogenesis and Migration in 3D
by Minimizing Plasma Membrane Curvature
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Fischer, A. R.; Waterman, Clare] NHLBI, NIH, Bethesda, MD 20892 USA.
[Elliot, Hunter] Harvard Univ, Sch Med, Boston, MA USA.
[Danuser, Gaudenz] UT Southwesterm Med Sch, Dallas, TX USA.
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PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
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GA AI6QE
UT WOS:000337000400064
ER
PT J
AU Lee, JC
Jiang, ZP
Hess, S
McGlinchey, RP
Yap, TL
Heinrich, F
AF Lee, Jennifer C.
Jiang, Zhiping
Hess, Sara
McGlinchey, Ryan P.
Yap, Thai Leong
Heinrich, Frank
TI Molecular Details of alpha-Synuclein Membrane Association Revealed by
Neutron Reflectometry
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Lee, Jennifer C.; Jiang, Zhiping; Hess, Sara; McGlinchey, Ryan P.; Yap, Thai Leong] NHLBI, Lab Mol Biophys, Bethesda, MD 20892 USA.
[Heinrich, Frank] Carnegie Mellon Univ, Dept Phys, Pittsburgh, PA 15213 USA.
[Heinrich, Frank] NIST, Ctr Neutron Res, Gaithersburg, MD 20899 USA.
NR 1
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PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
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UT WOS:000337000400086
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PT J
AU Belcher, J
Yao, YN
Berger, A
Mayer, ML
Lau, AY
AF Belcher, John
Yao, Yongneng
Berger, Anthony
Mayer, Mark L.
Lau, Albert Y.
TI NMDA and AMPA Receptor Ligand-Binding Domains Exhibit Subtype-Specific
Conformational Propensities
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Belcher, John; Lau, Albert Y.] Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA.
[Yao, Yongneng] Columbia Univ, New York, NY USA.
[Berger, Anthony] Univ Wisconsin, Madison, WI USA.
[Mayer, Mark L.] NICHHD, NIH, Bethesda, MD 20892 USA.
NR 0
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PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
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GA AI6QE
UT WOS:000337000400145
ER
PT J
AU Sunborger, A
Heyman, JA
Fang, SM
Chappie, JS
Hinshaw, JE
AF Sunborger, Anna
Heyman, Jurgen A.
Fang, Shunming
Chappie, Joshua S.
Hinshaw, Jenny E.
TI A Dynamin Mutant Defines a Super-Constricted Pre-Fission Step
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Sunborger, Anna; Heyman, Jurgen A.; Fang, Shunming; Hinshaw, Jenny E.] NIDDK, NIH, Bethesda, MD 20892 USA.
[Chappie, Joshua S.] Cornell Univ, Ithaca, NY USA.
NR 0
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PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
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EP 31A
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SC Biophysics
GA AI6QE
UT WOS:000337000400156
ER
PT J
AU Chung, HS
AF Chung, Hoi Sung
TI Transition-Path Times in Protein Folding from Single-Molecule FRET Hoi
Sung Chung
SO BIOPHYSICAL JOURNAL
LA English
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CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Chung, Hoi Sung] NIDDK, NIH, Bethesda, MD 20892 USA.
NR 0
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GA AI6QE
UT WOS:000337000400226
ER
PT J
AU Gopich, IV
AF Gopich, Irina V.
TI Theory of Single-Molecule Photon Sequences
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Gopich, Irina V.] NIDDK, NIH, Bethesda, MD 20892 USA.
NR 0
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PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
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GA AI6QE
UT WOS:000337000400225
ER
PT J
AU Hong, JJ
AF Hong, Jingjun
TI The Catalytic Subunit of the SWR1 Remodeler has a Histone Chaperone Role
for the H2A.Z-H2B Dimer
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Hong, Jingjun] NCI, NIH, Bethesda, MD 20892 USA.
NR 0
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PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
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GA AI6QE
UT WOS:000337000400232
ER
PT J
AU Kopkalli, Y
Smirnov, A
Knutson, JR
Davenport, L
AF Kopkalli, Yasemin
Smirnov, Aleksander
Knutson, Jay R.
Davenport, Lesley
TI Microheterogeneity of Telomeric DNA Guanine Residues: pH Dependent
Spectroscopic Studies of Fluorescently Labeled Model Trinucleotides
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Kopkalli, Yasemin; Davenport, Lesley] CUNY Brooklyn Coll, Brooklyn, NY 11210 USA.
[Smirnov, Aleksander; Knutson, Jay R.] NHLBI, Opt Spect Sect, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA.
NR 0
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PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
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UT WOS:000337000400332
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PT J
AU Naufer, MN
Furano, AV
Williams, MC
AF Naufer, M. Nabuan
Furano, Anthony V.
Williams, Mark C.
TI Human ORF1p-DNA Interactions Characterized by Single Molecule DNA
Stretching
SO BIOPHYSICAL JOURNAL
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DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Naufer, M. Nabuan; Williams, Mark C.] Northeastern Univ, Dept Phys, Boston, MA 02115 USA.
[Furano, Anthony V.] NIDDK, Lab Mol & Cellular Biol, NIH, Bethesda, MD 20892 USA.
NR 0
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GA AI6QE
UT WOS:000337000400376
ER
PT J
AU Chereji, RV
Morozov, AV
AF Chereji, Razvan V.
Morozov, Alexandre V.
TI Ubiquitous Nucleosome Unwrapping in the Yeast Genome
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Chereji, Razvan V.] NIH, Bethesda, MD 20892 USA.
[Morozov, Alexandre V.] Rutgers State Univ, Dept Phys, Piscataway, NJ 08854 USA.
RI Morozov, Alexandre/E-1984-2016
OI Morozov, Alexandre/0000-0003-2598-7000
NR 3
TC 0
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PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
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GA AI6QE
UT WOS:000337000400385
ER
PT J
AU Kimura, T
Mihailescu, M
Lynch, DL
Eldho, NV
Reggio, PH
Yeliseev, AA
Gawrisch, K
AF Kimura, Tomohiro
Mihailescu, Mihaela
Lynch, Diane L.
Eldho, Nadukkudy V.
Reggio, Patricia H.
Yeliseev, Alexei A.
Gawrisch, Klaus
TI Biophysical Properties of 2-Arachidonoylglycerol in a Lipid Matrix and
its Binding to Recombinant Cannabinoid Receptor CB2
SO BIOPHYSICAL JOURNAL
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DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Kimura, Tomohiro; Eldho, Nadukkudy V.; Yeliseev, Alexei A.; Gawrisch, Klaus] NIAAA, NIH, Bethesda, MD USA.
[Mihailescu, Mihaela] Univ Maryland, IBBR, Rockville, MD USA.
[Lynch, Diane L.; Reggio, Patricia H.] Univ N Carolina, Greensboro, NC 27412 USA.
NR 0
TC 1
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UT WOS:000337000400540
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PT J
AU Sirenko, S
Juhaszova, M
Liu, J
Ahmet, I
Sollott, SJ
Lakatta, EG
AF Sirenko, Syevda
Juhaszova, Magdalena
Liu, Jie
Ahmet, Ismayil
Sollott, Steven J.
Lakatta, Edward G.
TI Coupled-Clock Pacemaker System becomes Dysfunctional with Aging
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Sirenko, Syevda; Lakatta, Edward G.] NIA, Cardiovasc Biol Sect, NIH, Baltimore, MD 21224 USA.
[Juhaszova, Magdalena; Sollott, Steven J.] NIA, Cardio Protect Sect, NIH, Baltimore, MD 21224 USA.
[Liu, Jie] Univ Sydney, Dept Physiol, Sydney, NSW 2006, Australia.
[Ahmet, Ismayil] NIA, Translat Cardiovasc Studies Sect, NIH, Baltimore, MD 21224 USA.
NR 0
TC 1
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PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
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GA AI6QE
UT WOS:000337000400568
ER
PT J
AU Yang, DM
Lyashkov, AE
Ziman, BD
Lakatta, EG
AF Yang, Dongmei
Lyashkov, Alexey E.
Ziman, Bruce D.
Lakatta, Edward G.
TI CA(2+) Cycling Proteins Phosphorylation in Isolated Sinoatrial Nodal
Cells Modulates the Stochasticity of Spontaneous Diastolic Local CA(2+)
Releases which Regulate the Action Potential Cycle Length and its
Beat-To-Beat Variation
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Yang, Dongmei; Lyashkov, Alexey E.; Ziman, Bruce D.; Lakatta, Edward G.] NIA, NIH, Baltimore, MD 21224 USA.
NR 0
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PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
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GA AI6QE
UT WOS:000337000400567
ER
PT J
AU Younes, A
Lukyanenko, Y
Lyashkov, A
Tarasov, K
Sirenko, S
Ziman, B
Juhaszova, M
Graham, DR
Lakatta, EG
AF Younes, Antoine
Lukyanenko, Yevgeniya
Lyashkov, Alexey
Tarasov, Kirill
Sirenko, Syevda
Ziman, Bruce
Juhaszova, Magdalena
Graham, David R.
Lakatta, Edward G.
TI Phosphodiesterase Expression Pattern and Activity Partitioning in Lipid
Raft and in Non-Lipid-Raft Microenvironment in Cardiac Sinoatrial Nodal
Cells
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Younes, Antoine; Lukyanenko, Yevgeniya; Tarasov, Kirill; Sirenko, Syevda; Ziman, Bruce; Juhaszova, Magdalena; Lakatta, Edward G.] NIA, Baltimore, MD 21224 USA.
[Lyashkov, Alexey; Graham, David R.] JHU, Baltimore, MD USA.
NR 0
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PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
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SU 1
BP 111A
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GA AI6QE
UT WOS:000337000400566
ER
PT J
AU Yaniv, Y
Ahmet, I
Jie, L
Guiriba, TR
Okamoto, Y
Lakatta, EG
AF Yaniv, Yael
Ahmet, Ismayil
Jie, Liu
Guiriba, Toni-Rose
Okamoto, Yosuke
Lakatta, Edward G.
TI Fractal-Like Behavior of the Heart-Beat Intervals is Encoded within
Intrinsic Complexity of Pacemaker Cells Residing in the Sinoatrial Node
and Modulated by Autonomic Input to the Heart
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Yaniv, Yael; Ahmet, Ismayil; Guiriba, Toni-Rose; Okamoto, Yosuke; Lakatta, Edward G.] NIA, NIH, Baltimore, MD 21224 USA.
[Jie, Liu] Univ Sydney, Sydney, NSW 2006, Australia.
RI Yaniv, Yael/B-3311-2015
OI Yaniv, Yael/0000-0002-5183-6284
NR 0
TC 0
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PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
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GA AI6QE
UT WOS:000337000400642
ER
PT J
AU Cheng, RC
Chang, P
Fenollar-Ferrer, C
Stein, RA
Trone, K
Forrest, LR
Mchaourab, HS
Maduke, MC
AF Cheng, Ricky C.
Chang, Philip
Fenollar-Ferrer, Christina
Stein, Richard A.
Trone, Kristin
Forrest, Lucy R.
Mchaourab, Hassane S.
Maduke, Merritt C.
TI Monitoring Substrate-Driven Structural Changes in a CLC Chloride-Proton
Antiporter with Double Electron-Electron Resonance Spectroscopy
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Cheng, Ricky C.; Chang, Philip; Trone, Kristin; Maduke, Merritt C.] Stanford Univ, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA.
[Fenollar-Ferrer, Christina; Forrest, Lucy R.] NINDS, Computat Struct Biol Unit, Bethesda, MD 20892 USA.
[Stein, Richard A.; Mchaourab, Hassane S.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Med Ctr, Nashville, TN 37232 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 145A
EP 145A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000400720
ER
PT J
AU Courville, P
Mindell, JA
AF Courville, Pascal
Mindell, Joseph A.
TI Roles of Cytoplasmic Ions in Lysosomal Acidification
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Courville, Pascal; Mindell, Joseph A.] NINDS, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 147A
EP 147A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000400728
ER
PT J
AU Weston, M
AF Weston, Mary
TI Role of Candidate Counterions in Clathrin Coated Vesicle Acidification
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Weston, Mary] NINDS, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 147A
EP 147A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000400731
ER
PT J
AU Chittori, S
Kumar, J
Lomash, S
Zhao, HY
Schuck, P
Mayer, ML
AF Chittori, Sagar
Kumar, Janesh
Lomash, Suvendu
Zhao, Huaying
Schuck, Peter
Mayer, Mark L.
TI Role of Amino-Terminal Domain in the Assembly Mechanism of
Kainate-Subtype Glutamate Receptor Ion Channels
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Chittori, Sagar; Kumar, Janesh; Lomash, Suvendu; Mayer, Mark L.] NICHHD, NIH, Bethesda, MD 20892 USA.
[Zhao, Huaying; Schuck, Peter] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 151A
EP 151A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000400749
ER
PT J
AU Lomash, S
Zhao, HY
Glasser, C
Mayer, ML
Schuck, P
AF Lomash, Suvendu
Zhao, Huaying
Glasser, Carla
Mayer, Mark L.
Schuck, Peter
TI Investigating High Affinity Protein Self-Association by Fluorescence
Optical Sedimentation Velocity Analytical Ultracentrifugation
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Lomash, Suvendu; Glasser, Carla; Mayer, Mark L.] NICHHD, NIH, Bethesda, MD 20892 USA.
[Zhao, Huaying; Schuck, Peter] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 151A
EP 151A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000400750
ER
PT J
AU Mayer, M
Lomash, S
AF Mayer, Mark
Lomash, Suvendu
TI Calcium Flux Through AvGluR1: A Glutamate Receptor with a Potassium
Channel Selectivity Sequence
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Mayer, Mark; Lomash, Suvendu] NIH, Bethesda, MD 20892 USA.
NR 2
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 151A
EP 151A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000400748
ER
PT J
AU Li, MF
Harnish, E
Silberberg, SD
Swartz, KJ
AF Li, Mufeng
Harnish, Emily
Silberberg, Shai D.
Swartz, Kenton J.
TI Subtype-Specific Control of P2X Receptor Signaling by ATP and Magnesium
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Li, Mufeng; Harnish, Emily; Silberberg, Shai D.; Swartz, Kenton J.] NINDS, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 153A
EP 153A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000400761
ER
PT J
AU Stussman, RS
Chen, Y
AF Stussman, Rebecca S.
Chen, Yun
TI Fibroblast Phenotype Transformation by Cocultured Cancer Epithelial
Cells
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Stussman, Rebecca S.; Chen, Yun] NIH, Bethesda, MD 20892 USA.
[Stussman, Rebecca S.] Columbia Univ, New York, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 172A
EP 172A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000400851
ER
PT J
AU Heissler, SM
Billington, N
Sellers, JR
AF Heissler, Sarah M.
Billington, Neil
Sellers, James R.
TI Myosin-3B and its Light Chains
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Heissler, Sarah M.; Billington, Neil; Sellers, James R.] NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 178A
EP 178A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000401016
ER
PT J
AU Bird, JE
Takagi, Y
Billington, N
Heissler, SM
Friedman, TB
Sellers, JR
AF Bird, Jonathan E.
Takagi, Yasuharu
Billington, Neil
Heissler, Sarah M.
Friedman, Thomas B.
Sellers, James R.
TI Purification and Characterization of Myosin-15, the Molecular Motor
Mutated in DFNB3 Human Deafness
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Bird, Jonathan E.; Friedman, Thomas B.] NIDCD, Mol Genet Lab, Rockville, MD USA.
[Takagi, Yasuharu; Billington, Neil; Heissler, Sarah M.; Sellers, James R.] NHLBI, Lab Mol Physiol, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 2
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 179A
EP 179A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000401024
ER
PT J
AU Takagi, Y
Farrow, RE
Billington, N
Nagy, A
Batters, C
Yang, Y
Sellers, JR
Molloy, JE
AF Takagi, Yasuharu
Farrow, Rachel E.
Billington, Neil
Nagy, Attila
Batters, Chistopher
Yang, Yi
Sellers, James R.
Molloy, Justin E.
TI Myosin-10 Produces its Power-Stroke in Two Phases and Moves Processively
along a Single Actin Filament under Low-Load
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Takagi, Yasuharu; Billington, Neil; Nagy, Attila; Yang, Yi; Sellers, James R.] NIH, Bethesda, MD 20892 USA.
[Farrow, Rachel E.; Batters, Chistopher; Molloy, Justin E.] Natl Inst Med Res, MRC, London NW7 1AA, England.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 179A
EP 179A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000401021
ER
PT J
AU Arroyo, JO
Andrecka, J
Takagi, Y
Sellers, JR
Kukura, P
AF Arroyo, Jaime Ortega
Andrecka, Joanna
Takagi, Yasuharu
Sellers, James R.
Kukura, Philipp
TI Label-Free, All-Optical Detection, Imaging and Nanometric Tracking of
Single Proteins
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Arroyo, Jaime Ortega; Andrecka, Joanna; Kukura, Philipp] Univ Oxford, Dept Phys & Theoret Chem, Oxford, England.
[Takagi, Yasuharu; Sellers, James R.] NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 194A
EP 194A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000401093
ER
PT J
AU Andrecka, J
Ortega-Arroyo, J
Takagi, Y
Sellers, JR
Kukura, P
AF Andrecka, Joanna
Ortega-Arroyo, Jaime
Takagi, Yasuharu
Sellers, James R.
Kukura, Philipp
TI Revealing Myosin's Power Stroke with High-Speed Scattering
Interferometry
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Andrecka, Joanna; Ortega-Arroyo, Jaime; Kukura, Philipp] Univ Oxford, Dept Chem, Phys & Theoret Chem Lab, Oxford OX1 3QZ, England.
[Takagi, Yasuharu; Sellers, James R.] NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 197A
EP 197A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000401113
ER
PT J
AU Balijepalli, A
Vaz, C
Ettedgui, J
Cornio, AT
Robertson, JWF
Cheung, KP
Pastor, RW
Kasianowicz, JJ
AF Balijepalli, Arvind
Vaz, Canute
Ettedgui, Jessica
Cornio, Andrew T.
Robertson, Joseph W. F.
Cheung, Kin P.
Pastor, Richard W.
Kasianowicz, John J.
TI Quantifying Short-Lived Events in Multi-State Ionic Channel Measurements
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Balijepalli, Arvind; Vaz, Canute; Ettedgui, Jessica; Cornio, Andrew T.; Robertson, Joseph W. F.; Cheung, Kin P.; Kasianowicz, John J.] NIST, Gaithersburg, MD 20899 USA.
[Balijepalli, Arvind; Pastor, Richard W.] NIH, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 213A
EP 213A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000401189
ER
PT J
AU Ferguson, ML
Coulon, A
de Turris, V
Palangat, M
Chow, CC
Larson, DR
AF Ferguson, Matthew L.
Coulon, Antoine
de Turris, Valeria
Palangat, Murali
Chow, Carson C.
Larson, Daniel R.
TI Single Molecule Imaging In Vivo Determines Post-Transcriptional RNA
Processing Dynamics
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Ferguson, Matthew L.; Palangat, Murali; Larson, Daniel R.] NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA.
[Coulon, Antoine; Chow, Carson C.] NIDDK, Lab Biol Modeling, Bethesda, MD 20892 USA.
[de Turris, Valeria] Univ Rome, Ctr Life Nanosci, Rome, Italy.
RI Coulon, Antoine/A-9006-2012
NR 0
TC 0
Z9 0
U1 0
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 223A
EP 223A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000401242
ER
PT J
AU Fenollar-Ferrer, MC
Patti, M
Knoepfel, T
Werner, A
Forster, IC
Forrest, LR
AF Fenollar-Ferrer, Maria Cristina
Patti, Monica
Knoepfel, Thomas
Werner, Andreas
Forster, Ian C.
Forrest, Lucy R.
TI Structural Model of the Human Sodium-Phosphate Cotransporter NaPi-II
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Fenollar-Ferrer, Maria Cristina; Forrest, Lucy R.] NINDS, NIH, Bethesda, MD 20892 USA.
[Patti, Monica; Knoepfel, Thomas; Forster, Ian C.] Univ Zurich, Zurich, Switzerland.
[Werner, Andreas] Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 228A
EP 228A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000401269
ER
PT J
AU Rudnick, G
Tavoulari, S
Zhang, YW
DeWitt, D
Nagarajan, A
Rosado, E
Ravera, S
Kreuder, AE
Forrest, LR
Rhoades, E
AF Rudnick, Gary
Tavoulari, Sotiria
Zhang, Yuan-Wei
DeWitt, David
Nagarajan, Anu
Rosado, Edwin
Ravera, Silvia
Kreuder, Anna-Elisabeth
Forrest, Lucy R.
Rhoades, Elizabeth
TI The Role of Sodium Sites in LeuT Conformational Changes
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Rudnick, Gary; Tavoulari, Sotiria; Zhang, Yuan-Wei; DeWitt, David; Rosado, Edwin; Ravera, Silvia; Kreuder, Anna-Elisabeth; Rhoades, Elizabeth] Yale Univ, New Haven, CT USA.
[Nagarajan, Anu; Forrest, Lucy R.] NINDS, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 228A
EP 229A
PG 2
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000401271
ER
PT J
AU Lohr, C
Christensen, AL
Veshaguri, S
Tutkus, M
Iversen, L
Kemmer, G
Yaffe, D
Zollmann, T
Curran, P
Schuldiner, S
Tampe, R
Pomorski, T
Mindell, J
Stamou, D
AF Lohr, Christina
Christensen, Andreas Lauge
Veshaguri, Salome
Tutkus, Marijonas
Iversen, Lars
Kemmer, Gerdi
Yaffe, Dana
Zollmann, Tina
Curran, Patricia
Schuldiner, Shimon
Tampe, Robert
Pomorski, Thomas
Mindell, Joseph
Stamou, Dimitrios
TI Single Liposomes Used to Study the Activity of Individual Transporters
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Lohr, Christina; Christensen, Andreas Lauge] Univ Copenhagen, Dept Neurosci & Pharmacol, Copenhagen, Denmark.
[Veshaguri, Salome; Tutkus, Marijonas; Iversen, Lars; Stamou, Dimitrios] Univ Copenhagen, Dept Chem, DK-2100 Copenhagen, Denmark.
[Kemmer, Gerdi; Pomorski, Thomas] Univ Copenhagen, Dept Plant Biol & Biotechnol, Sect Transport Biol, Copenhagen, Denmark.
[Yaffe, Dana; Schuldiner, Shimon] Hebrew Univ Jerusalem, Dept Biol Chem, Jerusalem, Israel.
[Zollmann, Tina; Tampe, Robert] Goethe Univ Frankfurt, Bioctr, Inst Biochem, D-60054 Frankfurt, Germany.
[Curran, Patricia; Mindell, Joseph] NINDS, Membrane Transport Biophys Sect, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA.
RI Gunther Pomorski, Thomas/G-4804-2014; Kemmer, Gerdi
Christine/C-1691-2015; Iversen, Lars/C-5298-2011; Veshaguri,
Salome/F-8052-2016; Fachbereich14, Dekanat/C-8553-2015
OI Gunther Pomorski, Thomas/0000-0002-4889-0829; Kemmer, Gerdi
Christine/0000-0002-4686-5531; Iversen, Lars/0000-0002-1314-130X;
Veshaguri, Salome/0000-0002-7439-6373;
NR 8
TC 1
Z9 1
U1 0
U2 7
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 229A
EP 229A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000401273
ER
PT J
AU Noskov, S
Hermida, OT
Rostovtseva, T
Sergei, B
AF Noskov, Sergei
Hermida, Oscar Teijido
Rostovtseva, Tatiana
Sergei, Bezrukov
TI Mapping Conformational States in VDAC1 Channel: Complexity of Gating
Landscape
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Noskov, Sergei] Univ Calgary, Calgary, AB, Canada.
[Hermida, Oscar Teijido; Rostovtseva, Tatiana; Sergei, Bezrukov] Eunice Kennedy Shriver NICHD, Program Phys Biol, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 234A
EP 234A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000401300
ER
PT J
AU Zhao, HY
Mayer, ML
Schuck, P
AF Zhao, Huaying
Mayer, Mark L.
Schuck, Peter
TI Analysis of High-Affinity Protein Interactions by Fluorescence Optical
Analytical Ultracentrifugation
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Zhao, Huaying; Schuck, Peter] NIBIB, NIH, Bethesda, MD USA.
[Mayer, Mark L.] NICHD, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 236A
EP 236A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000401311
ER
PT J
AU Guo, M
Ehrlicher, A
Jensen, M
Moore, J
Lippincott-Schwartz, J
Mackintosh, F
Weitz, D
AF Guo, Ming
Ehrlicher, Allen
Jensen, Mikkel
Moore, Jeffrey
Lippincott-Schwartz, Jennifer
Mackintosh, Frederick
Weitz, David
TI Force Spectrum Microscopy Reveals Active Diffusive-Like Fluctuations in
Living Cells
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Guo, Ming; Ehrlicher, Allen; Jensen, Mikkel; Weitz, David] Harvard Univ, Cambridge, MA 02138 USA.
[Moore, Jeffrey] Boston Univ, Boston, MA 02215 USA.
[Lippincott-Schwartz, Jennifer] NIH, Bethesda, MD 20892 USA.
[Mackintosh, Frederick] Vrije Univ Amsterdam, Amsterdam, Netherlands.
RI guo, ming/D-4564-2015
NR 0
TC 0
Z9 0
U1 1
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 244A
EP 244A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000401350
ER
PT J
AU Pearlman, AH
Salvi, S
O'Hara, PB
Hebda, JA
AF Pearlman, Alexander H.
Salvi, Satyajeet
O'Hara, Patricia B.
Hebda, James A.
TI Stability and Dynamics of Alpha Crystallin Oligomers Probed by FRET and
FCS Reveal Persistent Oligomerization Under Dilute Conditions
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Pearlman, Alexander H.] NIH, Bethesda, MD 20892 USA.
[Salvi, Satyajeet] Hampshire Coll, Amherst, MA 01002 USA.
[O'Hara, Patricia B.; Hebda, James A.] Amherst Coll, Dept Chem, Amherst, MA 01002 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 247A
EP 247A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000401367
ER
PT J
AU Pant, K
Gorelick, RJ
Rouzina, I
Williams, MC
AF Pant, Kiran
Gorelick, Robert J.
Rouzina, Ioulia
Williams, Mark C.
TI Single Molecule Study of HIV-1 Reverse Transcriptase Polymerization
Activity in the Presence of NC
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Pant, Kiran; Williams, Mark C.] Northeastern Univ, Boston, MA 02115 USA.
[Gorelick, Robert J.] Leidos Biomed Res Inc, AIDS & Canc Virus Program, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Rouzina, Ioulia] Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 271A
EP 271A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000401494
ER
PT J
AU Harami, G
Seol, Y
In, J
Sarlos, K
Sun, YZ
Martina, M
Neuman, KC
Kovacs, M
AF Harami, Gabor
Seol, Yeonee
In, Junghoon
Sarlos, Kata
Sun, Yuze
Martina, Mate
Neuman, Keir C.
Kovacs, Mihaly
TI Domain Architecture of RecQ Helicase Defines Mechanochemical Linkage via
Multipartite Interactions with DNA Substrate during Unwinding Activity
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Harami, Gabor; Sarlos, Kata; Martina, Mate; Kovacs, Mihaly] Eotvos Lorand Univ, Budapest, Hungary.
[Seol, Yeonee; In, Junghoon; Neuman, Keir C.] NHLBI, Bethesda, MD 20892 USA.
[Sun, Yuze] Univ Texas Arlington, Arlington, TX 76019 USA.
RI Neuman, Keir/F-7400-2011
OI Neuman, Keir/0000-0002-0863-5671
NR 0
TC 0
Z9 0
U1 1
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 272A
EP 272A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000401501
ER
PT J
AU Perrin, BS
Fu, RQ
Venable, RM
Mihailescu, E
Grant, CV
Tian, Y
Opella, S
Pastor, RW
Cotten, M
AF Perrin, B. Scott, Jr.
Fu, Riqiang
Venable, Richard M.
Mihailescu, Ella
Grant, Chris V.
Tian, Ye
Opella, Stanley
Pastor, Richard W.
Cotten, Myriam
TI Antimicrobial Peptides Piscidin 1 and Piscidin 3 Kink at a Central
Glycine to Maximize their Hydrophobic Moments
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Perrin, B. Scott, Jr.; Venable, Richard M.; Pastor, Richard W.] NHLBI, Lab Computat Biol, NIH, Rockville, MD USA.
[Fu, Riqiang] Natl High Magnet Field Lab, Tallahassee, FL USA.
[Mihailescu, Ella] Univ Maryland, Inst Biosci & Biotechnol Res, Gaithersburg, MD USA.
[Grant, Chris V.; Tian, Ye; Opella, Stanley] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA.
[Cotten, Myriam] Hamilton Coll, Dept Chem, Clinton, NY 13323 USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 293A
EP 293A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000401613
ER
PT J
AU Lee, JC
McGlinchey, RP
Vargas, M
AF Lee, Jennifer C.
McGlinchey, Ryan P.
Vargas, Mercedes
TI Mimicking Lysosomal Degradation of alpha-Synuclein
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Lee, Jennifer C.; McGlinchey, Ryan P.; Vargas, Mercedes] NHLBI, Lab Mol Biophys, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 301A
EP 301A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000401651
ER
PT J
AU Banerjee, A
Berezhkovskii, A
Nossal, R
AF Banerjee, Anand
Berezhkovskii, Alexander
Nossal, Ralph
TI Modeling Nanoparticle Internalization via Receptor-Mediated Endocytosis
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Banerjee, Anand; Berezhkovskii, Alexander; Nossal, Ralph] NIH, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 1
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 309A
EP 309A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000401689
ER
PT J
AU Stern, M
Maltseva, LA
Juhaszova, M
Sollott, SJ
Lakatta, EG
Maltsev, VA
AF Stern, Michael
Maltseva, Larissa A.
Juhaszova, Magdalena
Sollott, Steven J.
Lakatta, Edward G.
Maltsev, Victor A.
TI Emergence and Synchronization of the "Calcium Clock'' in a 3-Dimensional
Model of a Sino-Atrial Node Cell with Explicit Channel Gating
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Stern, Michael; Maltseva, Larissa A.; Juhaszova, Magdalena; Sollott, Steven J.; Lakatta, Edward G.; Maltsev, Victor A.] NIA, NIH, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 318A
EP 318A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000401733
ER
PT J
AU Maltsev, VA
Maltsev, AV
Lakatta, EG
Stern, MD
AF Maltsev, Victor A.
Maltsev, Anna V.
Lakatta, Edward G.
Stern, Michael D.
TI Spatial Imperfection Encodes Functional Perfection: Success and Failure
of Calcium Release to Propagate Regulate Pacemaker Cell Function
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Maltsev, Victor A.; Lakatta, Edward G.; Stern, Michael D.] NIA, NIH, Baltimore, MD 21224 USA.
[Maltsev, Anna V.] Univ Bristol, Bristol, Avon, England.
NR 0
TC 2
Z9 2
U1 1
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 319A
EP 319A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000401738
ER
PT J
AU Yaniv, Y
Lyashkov, AE
Sirenko, S
Okamoto, Y
Guiriba, TR
Lakatta, EG
AF Yaniv, Yael
Lyashkov, Alexey E.
Sirenko, Syevda
Okamoto, Yosuke
Guiriba, Toni-Rose
Lakatta, Edward G.
TI The Coupled-Pacemaker Clock System of Sinoatrial Nodal Cells Regulates
Both the Action Potential Rate and Rhythm
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Yaniv, Yael; Lyashkov, Alexey E.; Sirenko, Syevda; Okamoto, Yosuke; Guiriba, Toni-Rose; Lakatta, Edward G.] NIA, NIH, Baltimore, MD 21224 USA.
RI Yaniv, Yael/B-3311-2015
OI Yaniv, Yael/0000-0002-5183-6284
NR 0
TC 0
Z9 0
U1 0
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 322A
EP 322A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000401754
ER
PT J
AU Zhang, F
Krepkiy, D
Bae, C
Moiseenkova-Bell, V
Hanson, S
Gorshkova, I
Pearce, L
Blumberg, PM
Kim, JI
Swartz, KJ
AF Zhang, Feng
Krepkiy, Dmitriy
Bae, Chanhyung
Moiseenkova-Bell, Vera
Hanson, Sonya
Gorshkova, Inna
Pearce, Larry
Blumberg, Peter M.
Kim, Jae Il
Swartz, Kenton J.
TI Lipid-Mediated Interaction of Double-Knot Toxin with TRPV1 Channels
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Zhang, Feng; Krepkiy, Dmitriy; Bae, Chanhyung; Hanson, Sonya; Gorshkova, Inna; Pearce, Larry; Blumberg, Peter M.; Swartz, Kenton J.] NIH, Bethesda, MD 20892 USA.
[Moiseenkova-Bell, Vera] CWRU, Cleveland, OH USA.
[Kim, Jae Il] GIST, Kwangju, South Korea.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 336A
EP 336A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000401815
ER
PT J
AU Toepfer, C
Sikkel, M
Caorsi, V
Copeland, O
Martinez, IT
West, T
Marston, S
Luther, P
Lyon, A
Macleod, K
Ferenczi, M
AF Toepfer, Christopher
Sikkel, Markus
Caorsi, Valentina
Copeland, O'Neal
Martinez, Iratxe Torre
West, Timothy
Marston, Steve
Luther, Pradeep
Lyon, Alexander
Macleod, Kenneth
Ferenczi, Michael
TI Effects of Chronic Myocardial Infarction on Cardiac Muscle Performance
and Structure In-Vivo and In-Vitro
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Toepfer, Christopher] NIH, Bethesda, MD 20892 USA.
[Sikkel, Markus; Caorsi, Valentina; Copeland, O'Neal; Martinez, Iratxe Torre; Marston, Steve; Luther, Pradeep; Lyon, Alexander; Macleod, Kenneth] Univ London Imperial Coll Sci Technol & Med, London, England.
[West, Timothy] Univ London Royal Vet Coll, London, England.
[Ferenczi, Michael] Nanyang Technol Univ, Singapore, Singapore.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 343A
EP 344A
PG 2
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000401853
ER
PT J
AU Kellogg, EH
Alushin, GM
Lander, GC
Baker, D
Nogales, E
AF Kellogg, Elizabeth H.
Alushin, Gregory M.
Lander, Gabriel C.
Baker, David
Nogales, Eva
TI Studying the Structural Origins of Microtubule Dynamic Instability
through Combining Computational Modeling and cryoEM
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Kellogg, Elizabeth H.; Nogales, Eva] Univ Calif Berkeley, Berkeley, CA 94720 USA.
[Alushin, Gregory M.] NHLBI, Cell Biol & Physiol Ctr, Bethesda, MD 20892 USA.
[Lander, Gabriel C.] Scripps Res Inst, San Diego, CA USA.
[Baker, David] Univ Washington, Seattle, WA 98195 USA.
NR 0
TC 0
Z9 0
U1 1
U2 4
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 351A
EP 351A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000402006
ER
PT J
AU Montecinos-Franjola, F
Sackett, DL
Schuck, P
AF Montecinos-Franjola, Felipe
Sackett, Dan L.
Schuck, Peter
TI Tubulin Heterodimers Reversibly Dissociate with Moderate Kinetics as
Demonstrated using Sedimentation Velocity Analytical Ultracentrifugation
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Montecinos-Franjola, Felipe; Sackett, Dan L.] NICHD, NIH, Bethesda, MD USA.
[Schuck, Peter] NIBIB, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 351A
EP 351A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000402005
ER
PT J
AU Hwang, LC
Vecchiarelli, AG
Han, YW
Mizuuchi, M
Harada, Y
Funnell, BE
Mizuuchi, K
AF Hwang, Ling Chin
Vecchiarelli, Anthony G.
Han, Yong Woon
Mizuuchi, Michiyo
Harada, Yoshie
Funnell, Barbara E.
Mizuuchi, Kiyoshi
TI Para Protein Pattern Formation Drives Bacterial Plasmid Segregation
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Hwang, Ling Chin; Vecchiarelli, Anthony G.; Mizuuchi, Michiyo; Mizuuchi, Kiyoshi] NIDDK, NIH, Bethesda, MD 20892 USA.
[Han, Yong Woon; Harada, Yoshie] Inst Integrated Cell Mat Sci WPI iCeMS, Kyoto, Japan.
[Funnell, Barbara E.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada.
NR 0
TC 0
Z9 0
U1 1
U2 5
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 362A
EP 362A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000402062
ER
PT J
AU Hsu, CJ
Lippincott-Schwartz, J
AF Hsu, Chih-Jung
Lippincott-Schwartz, Jennifer
TI HIV-1 Nef Employs Cellular Autophagy Machinery to Downregulate CD4
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Hsu, Chih-Jung; Lippincott-Schwartz, Jennifer] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 363A
EP 363A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000402068
ER
PT J
AU Perez, C
Faust, B
Mehdipour, AR
Francesconi, KA
Forrest, LR
Ziegler, C
AF Perez, Camilo
Faust, Belinda
Mehdipour, Ahmad R.
Francesconi, Kevin A.
Forrest, Lucy R.
Ziegler, Christine
TI Substrate Bound Outward-Open State of the Symporter BetP: Insights Into
Sodium and Substrate Binding and Coupling
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Perez, Camilo; Faust, Belinda; Mehdipour, Ahmad R.; Forrest, Lucy R.; Ziegler, Christine] Max Planck Inst Biophys, Frankfurt, Germany.
[Perez, Camilo] ETH, Zurich, Switzerland.
[Faust, Belinda] Univ Oxford, Oxford, England.
[Francesconi, Kevin A.] Karl Franzens Univ Graz, Graz, Austria.
[Forrest, Lucy R.] NINDS, NIH, Bethesda, MD 20892 USA.
[Ziegler, Christine] Univ Regensburg, D-93053 Regensburg, Germany.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 363A
EP 364A
PG 2
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000402070
ER
PT J
AU Anselmi, C
Zhou, WC
Pos, KM
Faraldo-Gomez, JD
AF Anselmi, Claudio
Zhou, Wenchang
Pos, K. Martin
Faraldo-Gomez, Jose D.
TI Alternating-Access Mechanism of the Proton-Drug Antiporter AcrB
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Anselmi, Claudio; Zhou, Wenchang; Faraldo-Gomez, Jose D.] NHLBI, Theoret Mol Biophys Sect, NIH, Bethesda, MD 20892 USA.
[Pos, K. Martin] Goethe Univ Frankfurt, Inst Biochem, D-60054 Frankfurt, Germany.
RI Fachbereich14, Dekanat/C-8553-2015
NR 0
TC 0
Z9 0
U1 0
U2 4
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 367A
EP 368A
PG 2
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000402090
ER
PT J
AU Leone, V
Pogoryelov, D
Meier, T
Grell, E
Faraldo-Gomez, JD
AF Leone, Vanessa
Pogoryelov, Denys
Meier, Thomas
Grell, Ernst
Faraldo-Gomez, Jose D.
TI Experimental Determination of the Ion Selectivity of an ATP-Synthase
Membrane Rotor by Isothermal Titration Calorimetry
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Leone, Vanessa; Faraldo-Gomez, Jose D.] NHLBI, Theoret Mol Biophys Sect, NIH, Bethesda, MD 20892 USA.
[Pogoryelov, Denys; Meier, Thomas] Max Planck Inst Biophys, Dept Biol Struct, Frankfurt, Germany.
[Grell, Ernst] Max Planck Inst Biophys, Dept Mol Membrane Biol, Frankfurt, Germany.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 372A
EP 372A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000402112
ER
PT J
AU Zhou, WC
Matthies, D
Anselmi, C
Meier, T
Faraldo-Gomez, JD
AF Zhou, Wenchang
Matthies, Doreeen
Anselmi, Claudio
Meier, Thomas
Faraldo-Gomez, Jose D.
TI On the Functional Differentiation of F- and V-Type Rotary Atpases Atomic
Mechanism of a Hybrid F/V Membrane Rotor
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Zhou, Wenchang; Anselmi, Claudio; Faraldo-Gomez, Jose D.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Matthies, Doreeen; Meier, Thomas] Max Planck Inst Biophys, Dept Biol Struct, Frankfurt, Germany.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 372A
EP 372A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000402113
ER
PT J
AU Liu, J
Chen, J
AF Liu, Jian
Chen, Jing
TI Spatio-Temporal Regulation of Mitotic Spindle Checkpoints
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Liu, Jian; Chen, Jing] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 377A
EP 377A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000402138
ER
PT J
AU Chandran, PL
Yuan, J
Horkey, F
Mertz, E
Dimitriadis, EK
AF Chandran, Preethi L.
Yuan, Jessica
Horkey, Ferenc
Mertz, Edward
Dimitriadis, Emilios K.
TI A Systematic, High Resolution Mapping of the Elastic Modulus of Mouse
Cartilage Matrix
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Chandran, Preethi L.; Yuan, Jessica; Dimitriadis, Emilios K.] NIBIB, BEPS, NIH, Bethesda, MD USA.
[Horkey, Ferenc] NICHD, STBB, NIH, Bethesda, MD USA.
[Mertz, Edward] NICHD, SPB, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 389A
EP 389A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000402201
ER
PT J
AU Lew, MD
Nikolaitchik, OA
Hu, WS
Moerner, WE
AF Lew, Matthew D.
Nikolaitchik, Olga A.
Hu, Wei-Shau
Moerner, W. E.
TI Precise Measurement of the Relative Position of RNA Dimers within
Virus-Like Particles using 2-Color 3D Super-Resolution Fluorescence
Microscopy
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Lew, Matthew D.; Moerner, W. E.] Stanford Univ, Stanford, CA 94305 USA.
[Nikolaitchik, Olga A.; Hu, Wei-Shau] NCI, Frederick, MD 21701 USA.
RI Lew, Matthew/D-6270-2012
OI Lew, Matthew/0000-0002-5614-3292
NR 4
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 399A
EP 399A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000402251
ER
PT J
AU Yu, XZ
Strub, MP
Barnard, TJ
Noinaj, N
Piszczek, G
Buchanan, SK
Taraska, JW
AF Yu, Xiaozhen
Strub, Marie-Paule
Barnard, Travis J.
Noinaj, Nicholas
Piszczek, Grzegorz
Buchanan, Susan K.
Taraska, Justin W.
TI An Engineered Palette of Metal Ion Quenchable Fluorescent Proteins
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Yu, Xiaozhen; Strub, Marie-Paule; Piszczek, Grzegorz; Taraska, Justin W.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Barnard, Travis J.; Noinaj, Nicholas; Buchanan, Susan K.] NIDDK, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 418A
EP 418A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000402348
ER
PT J
AU Marinelli, F
Faraldo-Gomez, JD
AF Marinelli, Fabrizio
Faraldo-Gomez, Jose D.
TI Molecular Basis for Sodium Versus Calcium Binding in the Sodium-Calcium
Exchanger
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Marinelli, Fabrizio; Faraldo-Gomez, Jose D.] NHLBI, Theoret Mol Biophys Sect, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 428A
EP 428A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000402400
ER
PT J
AU Miranda, P
Giraldez, T
Holmgren, M
AF Miranda, Pablo
Giraldez, Teresa
Holmgren, Miguel
TI Divalent Cation-Dependent Motion of the BK Channel Gating-Ring Reported
by State Dependent FRET
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Miranda, Pablo; Holmgren, Miguel] NINDS, Bethesda, MD 20892 USA.
[Giraldez, Teresa] HUNSC, Div Res, Tenerife, Spain.
NR 5
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 436A
EP 437A
PG 2
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000402443
ER
PT J
AU Truex, K
Chung, HS
Eaton, WA
Louis, J
AF Truex, Katherine
Chung, Hoi Sung
Eaton, William A.
Louis, John
TI Single Molecule FRET Studies of DNA Hairpin Folding
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Truex, Katherine; Chung, Hoi Sung; Eaton, William A.; Louis, John] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 2
U2 14
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 439A
EP 439A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000402457
ER
PT J
AU Tian, Y
Schwieters, C
Opella, SJ
Marassi, FM
AF Tian, Ye
Schwieters, Charles
Opella, Stanley J.
Marassi, Francesca M.
TI NMR-Restrained Protein Structure Calculations in Implicit Environment
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Tian, Ye; Marassi, Francesca M.] Sanford Burnham Med Res Inst, La Jolla, CA USA.
[Tian, Ye] Univ Calif San Diego, La Jolla, CA 92093 USA.
[Schwieters, Charles] NIH, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
[Opella, Stanley J.] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 462A
EP 462A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000402571
ER
PT J
AU Dangkulwanich, M
Ishibashi, T
Liu, SX
Kireeva, ML
Lubkowska, L
Kahlev, M
Bustamante, CJ
AF Dangkulwanich, Manchuta
Ishibashi, Toyotaka
Liu, Shixin
Kireeva, Maria L.
Lubkowska, Lucyna
Kahlev, Mikhail
Bustamante, Carlos J.
TI Complete Dissection of Transcription Elongation Reveals Slow
Translocation of RNA Polymerase II in a Linear Ratchet Mechanism
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Dangkulwanich, Manchuta; Ishibashi, Toyotaka; Liu, Shixin; Bustamante, Carlos J.] Univ Calif Berkeley, Berkeley, CA USA.
[Kireeva, Maria L.; Lubkowska, Lucyna; Kahlev, Mikhail] NCI, Frederick, MD USA.
NR 0
TC 1
Z9 1
U1 0
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 485A
EP 486A
PG 2
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000402691
ER
PT J
AU Imashimizu, M
Oshima, T
Takahashi, H
Lubkowska, L
Kashlev, M
AF Imashimizu, Masahiko
Oshima, Taku
Takahashi, Hiroki
Lubkowska, Lucyna
Kashlev, Mikhail
TI Direct Assessment of Transcription Fidelity by RNA Sequencing
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Imashimizu, Masahiko; Lubkowska, Lucyna; Kashlev, Mikhail] NCI, NIH, Frederick, MD 21701 USA.
[Oshima, Taku] NAIST, Nara, Japan.
[Takahashi, Hiroki] Chiba Univ, Chiba, Japan.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 486A
EP 486A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000402694
ER
PT J
AU Aksoyoglu, MA
Gurnev, P
Parsegian, VA
AF Aksoyoglu, M. Alphan
Gurnev, Philip
Parsegian, V. Adrian
TI Molecular Competition between Large and Small Polyethylene-Glycols
(PEGs) Partitioning into OMPC Porin Channels
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Aksoyoglu, M. Alphan; Gurnev, Philip; Parsegian, V. Adrian] Univ Massachusetts, Amherst, MA 01003 USA.
[Gurnev, Philip] NICHD, PPB, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 4
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 499A
EP 499A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000402765
ER
PT J
AU Roark, TC
Hermida, OT
Rostovtseva, TK
Gurnev, PA
Petrache, HI
Bezrukov, SM
AF Roark, Torri C.
Hermida, Oscar Teijido
Rostovtseva, Tatiana K.
Gurnev, Philip A.
Petrache, Horia I.
Bezrukov, Sergey M.
TI Correlations of Specific Ionic Effects using Ion Channels and Surface
Charge Measurements
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Roark, Torri C.; Petrache, Horia I.] Indiana Univ Purdue Univ, Dept Phys, Indianapolis, IN 46205 USA.
[Roark, Torri C.; Hermida, Oscar Teijido; Rostovtseva, Tatiana K.; Gurnev, Philip A.; Bezrukov, Sergey M.] NICHHD, NIH, Bethesda, MD 20892 USA.
[Gurnev, Philip A.] Univ Massachusetts, Dept Phys, Amherst, MA 01003 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 499A
EP 499A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000402764
ER
PT J
AU Morin-Leisk, J
Hinshaw, J
AF Morin-Leisk, Jeanne
Hinshaw, Jenny
TI Mitofusin Proteins Tether Proteoliposomes as Shown by Cryo-EM
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Morin-Leisk, Jeanne; Hinshaw, Jenny] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 504A
EP 504A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000402789
ER
PT J
AU Sodt, AJ
Pastor, RW
AF Sodt, Alexander J.
Pastor, Richard W.
TI Quantitative Molecular Modeling of Membrane Curvature Induction by an
Amphipathic Helix
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Sodt, Alexander J.; Pastor, Richard W.] NHLBI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 505A
EP 505A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000402797
ER
PT J
AU Busse, BL
Bezrukov, L
Lee, J
Blank, PS
Pierce, S
Zimmerberg, J
AF Busse, Brad L.
Bezrukov, Ludmila
Lee, Jinmin
Blank, Paul S.
Pierce, Susan
Zimmerberg, Joshua
TI Proteomic Imaging of Plasma Membranes of Antigen-Activated B Lymphocytes
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Busse, Brad L.; Bezrukov, Ludmila; Lee, Jinmin; Blank, Paul S.; Pierce, Susan; Zimmerberg, Joshua] NIH, Bethesda, MD 20892 USA.
RI Bezrukov, Leonid/M-5654-2013
NR 0
TC 0
Z9 0
U1 0
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 519A
EP 519A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000402862
ER
PT J
AU Maltsev, A
Yaniv, Y
Stern, M
Lakatta, E
Maltsev, V
AF Maltsev, Anna
Yaniv, Yael
Stern, Michael
Lakatta, Edward
Maltsev, Victor
TI Local Calcium Dynamics Stabilize NCX Current in an Integrated Calcium
Cycling and Membrane Model
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Maltsev, Anna] Univ Bristol, Bristol, Avon, England.
[Yaniv, Yael; Stern, Michael; Lakatta, Edward; Maltsev, Victor] NIA, NIH, Baltimore, MD 21224 USA.
RI Yaniv, Yael/B-3311-2015
OI Yaniv, Yael/0000-0002-5183-6284
NR 0
TC 0
Z9 0
U1 0
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 531A
EP 531A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000403033
ER
PT J
AU Landrau, AAD
Holmgren, M
AF Landrau, Angel A. de la Cruz
Holmgren, Miguel
TI Locking the Open State of a Voltage-Dependent Concatemer Potassium
Channel with Metal Bridges
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Landrau, Angel A. de la Cruz] Univ Cent Caribe, Bayamon, PR USA.
[Holmgren, Miguel] NINDS, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 537A
EP 537A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000403064
ER
PT J
AU Lopez-Rodriguez, AM
Venkataraman, G
Holmgren, M
AF Lopez-Rodriguez, Angelica M.
Venkataraman, Gaurav
Holmgren, Miguel
TI Shaker Kv Channel's Sugar Remotion in Real-Time
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Lopez-Rodriguez, Angelica M.; Venkataraman, Gaurav; Holmgren, Miguel] NINDS, NIH, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 537A
EP 537A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000403063
ER
PT J
AU Tong, XH
Lopez, W
Ayad, WA
Yu, L
Lopez-Rodriguez, A
Harris, AL
Contreras, JE
AF Tong Xuhui
Lopez, William
Ayad, Wafaa A.
Yu Liu
Lopez-Rodriguez, Angelica
Harris, Andrew L.
Contreras, Jorge E.
TI On the Use of Chemical Modification to Determine Connexin Hemichannel
Topology and Function
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Tong Xuhui; Lopez, William; Ayad, Wafaa A.; Yu Liu; Harris, Andrew L.; Contreras, Jorge E.] Rutgers State Univ, New Jersey Med Sch, Newark, NJ 07102 USA.
[Tong Xuhui] Bengbu Med Coll, Bengbu, Anhui, Peoples R China.
[Lopez-Rodriguez, Angelica] NINDS, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 556A
EP 556A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000403155
ER
PT J
AU Barua, B
Nagy, A
Sellers, JR
Hitchcock-DeGregori, SE
AF Barua, Bipasha
Nagy, Attila
Sellers, James R.
Hitchcock-DeGregori, Sarah E.
TI Regulation of Nonmuscle Myosin II by Tropomyosin Isoforms
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Barua, Bipasha; Hitchcock-DeGregori, Sarah E.] Rutgers State Univ, Robert Wood Johnson Med Sch, Piscataway, NJ 08854 USA.
[Nagy, Attila; Sellers, James R.] NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 568A
EP 568A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000403213
ER
PT J
AU Kim, JH
Ren, YX
Li, S
Kee, Y
Zhang, GF
Robinson, D
Chen, E
AF Kim, Ji Hoon
Ren, Yixin
Li, Shuo
Kee, Yee
Zhang, Guofeng
Robinson, Douglas
Chen, Elizabeth
TI Myosin II Functions as a Direct Mechanosensor for Intercellular Invasion
during Cell-Cell Fusion
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Kim, Ji Hoon; Ren, Yixin; Li, Shuo; Kee, Yee; Robinson, Douglas; Chen, Elizabeth] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Zhang, Guofeng] Natl Inst Biomed Imaging & Bioengn, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 574A
EP 574A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000403241
ER
PT J
AU Sanchez-Rodriguez, JE
Miranda-Fernandez, P
Holmgren, M
Bezanilla, F
AF Sanchez-Rodriguez, Jorge E.
Miranda-Fernandez, Pablo
Holmgren, Miguel
Bezanilla, Francisco
TI Conformational Rearrangements of the Na+/K+ ATPase During Na+
Occlusion/Deocclusion Transitions Assessed by Site-Directed Fluorescence
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Sanchez-Rodriguez, Jorge E.; Bezanilla, Francisco] Univ Chicago, Chicago, IL 60637 USA.
[Miranda-Fernandez, Pablo; Holmgren, Miguel] NINDS, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 4
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 582A
EP 582A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000403284
ER
PT J
AU Nagarajan, A
Woolf, TB
AF Nagarajan, Anu
Woolf, Thomas B.
TI Environmental Influences on States: Molecular Dynamics Simulations of
SERCA
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Nagarajan, Anu] NINDS, NIH, Bethesda, MD 20892 USA.
[Woolf, Thomas B.] Johns Hopkins Univ, Dept Physiol, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 584A
EP 584A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000403294
ER
PT J
AU Hermida, OT
Noskov, SY
Ujwal, R
Abramson, J
Eddy, MT
Griffin, RG
Bezrukov, SM
Rostovtseva, TK
AF Hermida, Oscar Teijido
Noskov, Sergei Yu
Ujwal, Rachna
Abramson, Jeff
Eddy, Matthew T.
Griffin, Robert G.
Bezrukov, Sergey M.
Rostovtseva, Tatiana K.
TI Functional, Structural, and Computational Approaches to the Molecular
Mechanism of Vdac Gating
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Hermida, Oscar Teijido; Bezrukov, Sergey M.; Rostovtseva, Tatiana K.] NIH, Program Phys Biol, Bethesda, MD 20892 USA.
[Noskov, Sergei Yu] Univ Calgary, Dept Biol Sci, Inst Biocomplex & Bioinformat, Calgary, AB T2N 1N4, Canada.
[Ujwal, Rachna; Abramson, Jeff] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USA.
[Eddy, Matthew T.; Griffin, Robert G.] MIT, Dept Chem, Francis Bitter Magnet Lab, Cambridge, MA 02139 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 590A
EP 590A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000403326
ER
PT J
AU Jacobs, D
Kuszak, AJ
Buchanan, SK
Bezrukov, SM
Rostovtseva, TK
Gurnev, PA
AF Jacobs, Daniel
Kuszak, Adam J.
Buchanan, Susan K.
Bezrukov, Sergey M.
Rostovtseva, Tatiana K.
Gurnev, Philip A.
TI Investigating Tom40 Structure and Function Relationship using Single
Channel Analysis
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Jacobs, Daniel; Kuszak, Adam J.; Buchanan, Susan K.] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Jacobs, Daniel; Bezrukov, Sergey M.; Rostovtseva, Tatiana K.; Gurnev, Philip A.] NICHD, Program Phys Biol, NIH, Bethesda, MD USA.
[Gurnev, Philip A.] UMass Amherst, Dept Phys, Amherst, MA USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 590A
EP 590A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000403324
ER
PT J
AU Rostovtseva, TK
Gurnev, PA
Yap, TL
Lee, JC
Bezrukov, SM
AF Rostovtseva, Tatiana K.
Gurnev, Philip A.
Yap, Thai Leong
Lee, Jennifer C.
Bezrukov, Sergey M.
TI Parkinson Disease-Associated Protein alpha-Synuclein Blocks VDAC
Providing New Insights into Mitochondrial Toxicity
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Rostovtseva, Tatiana K.; Gurnev, Philip A.; Bezrukov, Sergey M.] NICHD, NIH, Bethesda, MD USA.
[Gurnev, Philip A.] Univ Massachusetts, Amhers, MA USA.
[Yap, Thai Leong; Lee, Jennifer C.] NHLBI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 590A
EP 590A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000403327
ER
PT J
AU DeHart, DN
Gooz, M
Rostovtseva, TK
Sheldon, KL
Lemasters, JJ
Maldonado, EN
AF DeHart, David N.
Gooz, Monika
Rostovtseva, Tatiana K.
Sheldon, Kely L.
Lemasters, John J.
Maldonado, Eduardo N.
TI Antagonists of the Inhibitory Effect of Free Tubulin on VDAC Induce
Oxidative Stress and Mitochondrial Dysfunction
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [DeHart, David N.; Gooz, Monika; Lemasters, John J.] Med Univ S Carolina, Charleston, SC 29425 USA.
[Rostovtseva, Tatiana K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Sheldon, Kely L.] Johns Hopkins Univ, W Harry Feinstein Dept Mol Microbiol & Immunol, Baltimore, MD USA.
[Maldonado, Eduardo N.] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA.
NR 0
TC 0
Z9 0
U1 2
U2 5
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 591A
EP 591A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000403328
ER
PT J
AU Guay, MD
Czaja, W
Leapman, RD
AF Guay, Matthew D.
Czaja, Wojciech
Leapman, Richard D.
TI Compressed Sensing Methods for Electron Tomography of Cellular Structure
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Guay, Matthew D.] Univ Maryland, Dept Appl Math & Sci Computat, College Pk, MD 20742 USA.
[Czaja, Wojciech] Univ Maryland, Dept Math, College Pk, MD 20742 USA.
[Leapman, Richard D.] NIBIB, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 598A
EP 599A
PG 2
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000403367
ER
PT J
AU Bartesaghi, A
Pierson, J
Rao, P
Banerjee, S
Borgnia, M
Yu, LB
Earl, L
Alink, M
Milne, J
Subramaniam, S
AF Bartesaghi, Alberto
Pierson, Jason
Rao, Prashant
Banerjee, Soojay
Borgnia, Mario
Yu, Lingbo
Earl, Lesley
Alink, Michael
Milne, Jacqueline
Subramaniam, Sriram
TI Structure Determination of Small Macromolecular Complexes by
Cryo-Electron Microscopy
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Bartesaghi, Alberto; Pierson, Jason; Rao, Prashant; Banerjee, Soojay; Borgnia, Mario; Yu, Lingbo; Earl, Lesley; Alink, Michael; Milne, Jacqueline; Subramaniam, Sriram] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 601A
EP 601A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000403382
ER
PT J
AU Pfeifer, CR
Shomorony, A
Zhang, GF
Aronova, MA
Leapman, RD
AF Pfeifer, Charlotte R.
Shomorony, Andre
Zhang, Guofeng
Aronova, Maria A.
Leapman, Richard D.
TI Serial Block-Face Scanning Electron Microscopy for Nanoscale
Characterization of Tissue Ultrastructure
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Pfeifer, Charlotte R.; Shomorony, Andre; Zhang, Guofeng; Aronova, Maria A.; Leapman, Richard D.] NIBIB, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 601A
EP 601A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000403380
ER
PT J
AU Rice, BJ
Abdus-Shakur, T
Curtis, KA
Klauda, JB
Venable, RM
Pastor, RW
Chandran, PL
AF Rice, Bria J.
Abdus-Shakur, Tasneem
Curtis, Kimberly A.
Klauda, Jeffrey B.
Venable, Richard M.
Pastor, Richard W.
Chandran, Preethi L.
TI Polyethylenimine: Experimental and Simulation Study of Polymer
Biophysics During Ph Buffering
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Rice, Bria J.; Abdus-Shakur, Tasneem; Curtis, Kimberly A.; Chandran, Preethi L.] Howard Univ, Washington, DC 20059 USA.
[Klauda, Jeffrey B.] Univ Maryland, College Pk, MD 20742 USA.
[Venable, Richard M.; Pastor, Richard W.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 617A
EP 617A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000403462
ER
PT J
AU Baydyuk, M
Wu, XS
Sheng, JS
He, LM
Wu, LG
AF Baydyuk, Maryna
Wu, Xinsheng
Sheng, Jiansong
He, Liming
Wu, Ling-Gang
TI BDNF Modulates Presynaptic Functions at a Central Synapse
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Baydyuk, Maryna; Wu, Xinsheng; Sheng, Jiansong; He, Liming; Wu, Ling-Gang] NINDS, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 628A
EP 629A
PG 2
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000403521
ER
PT J
AU Sirenko, S
Ahmet, I
Lakatta, EG
AF Sirenko, Syevda
Ahmet, Ismayil
Lakatta, Edward G.
TI PLB Drives the Kinetics of the Ca2+ Clock in Mouse Isolated Sinoatrial
Nodal Cells and the Intrinsic Heart Rate in vivo
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Sirenko, Syevda; Ahmet, Ismayil; Lakatta, Edward G.] NIA, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 631A
EP 631A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000403534
ER
PT J
AU Lyman, ER
Sodt, A
Gawrisch, K
Pastor, R
AF Lyman, Edward R.
Sodt, Alex
Gawrisch, Klaus
Pastor, Richard
TI The Molecular Structure of the Liquid Ordered Phase
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Lyman, Edward R.] Univ Delaware, Newark, DE USA.
[Sodt, Alex; Gawrisch, Klaus; Pastor, Richard] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 634A
EP 634A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000403546
ER
PT J
AU Mills, M
Neuman, K
AF Mills, Maria
Neuman, Keir
TI ATP Binding Induced Conformational Change in RecQ Helicase
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Mills, Maria; Neuman, Keir] NHLBI, Lab Single Mol Biophys, NIH, Bethesda, MD 20892 USA.
RI Neuman, Keir/F-7400-2011
OI Neuman, Keir/0000-0002-0863-5671
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 648A
EP 649A
PG 2
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000403620
ER
PT J
AU Ganesan, SJ
Schneider, J
Blumenthal, R
Matysiak, S
AF Ganesan, Sai Janani
Schneider, Joel
Blumenthal, Robert
Matysiak, Silvina
TI Role of Environment in Protein Folding
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Ganesan, Sai Janani; Matysiak, Silvina] Univ Maryland, College Pk, MD 20742 USA.
[Schneider, Joel; Blumenthal, Robert] NCI, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 669A
EP 669A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000403734
ER
PT J
AU Nguyen, TA
Veetil, JV
Sarkar, P
Vogel, SS
AF Nguyen, Tuan A.
Veetil, Jithesh V.
Sarkar, Pabak
Vogel, Steven S.
TI Fluorescence Polarization and Fluctuation Analysis Reveals Covert
Changes in CaMKII Holoenzyme Organization Triggered by Calmodulin and
Camkiintide
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Nguyen, Tuan A.; Veetil, Jithesh V.; Sarkar, Pabak; Vogel, Steven S.] NIAAA, NIH, Rockville, MD 20852 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 679A
EP 679A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000403784
ER
PT J
AU Sarkar, P
Davis, K
Puhl, HL
Veetil, JV
Nguyen, TA
Vogel, SS
AF Sarkar, Pabak
Davis, Kaitlin
Puhl, Henry L., III
Veetil, Jithesh V.
Nguyen, Tuan A.
Vogel, Steven S.
TI Positive Cooperativity and T286 Autophosphorylation is Observed in a
Dimeric Mutant of Calcium-Calmodulin Dependent Protein Kinase II
(CaMKII)
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Sarkar, Pabak; Davis, Kaitlin; Puhl, Henry L., III; Veetil, Jithesh V.; Nguyen, Tuan A.; Vogel, Steven S.] NIAAA, NIH, Rockville, MD 20852 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 679A
EP 679A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000403785
ER
PT J
AU Veetil, JV
Davis, K
Puhl, HL
Nguyen, TA
Sarkar, P
Vogel, SS
AF Veetil, Jithesh V.
Davis, Kaitlin
Puhl, Henry L., III
Nguyen, Tuan A.
Sarkar, Pabak
Vogel, Steven S.
TI Characterization of Calcium-Calmodulin Kinase II Inhibitor Protein
(CaMKIIN) by Fluorescence Polarization and Fluctuation Analysis
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Veetil, Jithesh V.; Davis, Kaitlin; Puhl, Henry L., III; Nguyen, Tuan A.; Sarkar, Pabak; Vogel, Steven S.] NIAAA, NIH, Rockville, MD 20852 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 679A
EP 680A
PG 2
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000403786
ER
PT J
AU Piszczek, G
AF Piszczek, Grzegorz
TI The Oligomeric State of Human Alpha-Defensin 1 in Solution
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Piszczek, Grzegorz] NHLBI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 681A
EP 681A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000403793
ER
PT J
AU Hategan, AP
Steiner, J
Dimitriadis, EK
Nath, A
AF Hategan, Alina Popescu
Steiner, Joseph
Dimitriadis, Emilios K.
Nath, Avindra
TI HIV-Tat Protein Enhances Amyloid Beta Peptide Aggregation
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Hategan, Alina Popescu; Steiner, Joseph; Dimitriadis, Emilios K.; Nath, Avindra] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 683A
EP 683A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000403802
ER
PT J
AU Hoogerheide, DP
Golovchenko, JA
AF Hoogerheide, David P.
Golovchenko, Jene A.
TI Universal Behavior of DNA Escape, Drift, and Diffusion in Nanopores
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Hoogerheide, David P.] NIST, Ctr Neutron Res, Gaithersburg, MD 20899 USA.
[Hoogerheide, David P.] NICHHD, NIH, Bethesda, MD 20892 USA.
[Golovchenko, Jene A.] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 695A
EP 695A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000403862
ER
PT J
AU Lorieau, JL
Louis, JM
Schwieters, CD
Bax, A
AF Lorieau, Justin L.
Louis, John M.
Schwieters, Charles D.
Bax, Ad
TI Influenza Membrane Fusion as Viewed from the Structure and Dynamics of
the Full-Length Hemagglutinin Fusion Domain
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Lorieau, Justin L.] Univ Illinois, Chicago, IL USA.
[Louis, John M.; Bax, Ad] NIDDK, NIH, Bethesda, MD 20892 USA.
[Schwieters, Charles D.] NIH, CIT, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 2
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 707A
EP 707A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000404042
ER
PT J
AU Roche, J
Louis, JM
Bax, A
AF Roche, Julien
Louis, John M.
Bax, Ad
TI GP41 Ectodomain Dissociates and Forms a Stable Monomer on Phospholipid
Vesicles and Detergent Micelles: Implication for the HIV-1 Env-Mediated
Membrane Fusion
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Roche, Julien; Louis, John M.; Bax, Ad] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 708A
EP 708A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000404046
ER
PT J
AU Soubias, O
Northup, JK
Hines, KG
Teague, WE
Gawrisch, K
AF Soubias, Olivier
Northup, John K.
Hines, Kirk G.
Teague, Walter E.
Gawrisch, Klaus
TI Rhodopsin Crowding in Model Lipid Bilayers - Functional Implications
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Soubias, Olivier; Northup, John K.; Hines, Kirk G.; Teague, Walter E.; Gawrisch, Klaus] NIH, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 715A
EP 715A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000404081
ER
PT J
AU Chen, Y
Tangrea, MA
Rosenberg, AZ
Du, Q
Emmert-Buck, MA
AF Chen, Yun
Tangrea, Michael A.
Rosenberg, Avi Z.
Du, Qiang
Emmert-Buck, Michael A.
TI Diffusion Discrepancy between Stroma of Tumor and Normal Tissues
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Chen, Yun; Tangrea, Michael A.; Rosenberg, Avi Z.; Du, Qiang; Emmert-Buck, Michael A.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 734A
EP 734A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000404166
ER
PT J
AU Kraft, LJ
Nguyen, TA
Vogel, SS
Kenworthy, AK
AF Kraft, Lewis J.
Nguyen, Tuan A.
Vogel, Steven S.
Kenworthy, Anne K.
TI Size, Stoichiometry, and Organization of Soluble LC3-Associated
Complexes
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Kraft, Lewis J.; Kenworthy, Anne K.] Vanderbilt Univ, Nashville, TN 37235 USA.
[Nguyen, Tuan A.; Vogel, Steven S.] NIH, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 734A
EP 735A
PG 2
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000404171
ER
PT J
AU Zamanian, M
Bae, C
Tilley, D
Gupta, K
Sack, J
Yarov-Yarovoy, V
Kim, JI
Swartz, K
AF Zamanian, Maryam
Bae, Chanhyung
Tilley, Drew
Gupta, Kanchan
Sack, Jon
Yarov-Yarovoy, Vladimir
Kim, Jae Ii
Swartz, Kenton
TI Common Interaction Surfaces for Tarantula Toxins Targeting Kv and ASIC
Channels
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Zamanian, Maryam] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
[Bae, Chanhyung; Gupta, Kanchan; Swartz, Kenton] NINDS, Mol Physiol & Biophys Sect, NIH, Bethesda, MD 20892 USA.
[Tilley, Drew; Sack, Jon; Yarov-Yarovoy, Vladimir] Univ Calif Davis, Dept Physiol & Membrane Biol, Davis, CA 95616 USA.
[Kim, Jae Ii] Gwangju Inst Sci & Technol, Dept Life Sci, Kwangju, South Korea.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 737A
EP 738A
PG 2
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000404185
ER
PT J
AU Nguyen, HM
Chhabra, S
Chang, SC
Huq, RU
Tanner, MR
Londono, LM
Gindin, M
Hotez, PJ
Mohanty, B
Iadonato, SP
Gutman, GA
Beeton, C
Pennington, MW
Norton, RS
Chandy, KG
AF Nguyen, Hai M.
Chhabra, Sandeep
Chang, Shih Chieh
Huq, Redwan U.
Tanner, Mark R.
Londono, Luz M.
Gindin, Mariel
Hotez, Peter J.
Mohanty, Biswaranjan
Iadonato, Shawn P.
Gutman, George A.
Beeton, Christine
Pennington, Michael W.
Norton, Raymond S.
Chandy, K. George
TI Kv1.3-Blocking Peptides from Parasitic Worms Exhibit Immunomodulatory
Function
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Nguyen, Hai M.; Gutman, George A.; Chandy, K. George] Univ Calif Davis, Davis, CA 95616 USA.
[Chhabra, Sandeep; Chang, Shih Chieh; Mohanty, Biswaranjan; Norton, Raymond S.] Monash Univ, Parkville, Vic, Australia.
[Huq, Redwan U.; Tanner, Mark R.; Beeton, Christine] Baylor Coll Med, Houston, TX 77030 USA.
[Londono, Luz M.; Iadonato, Shawn P.] Kineta Inc, Seattle, WA USA.
[Gindin, Mariel] George Washington Univ, Washington, DC USA.
[Gindin, Mariel] NIH, Lab Malaria & Vector Res, Bethesda, MD 20892 USA.
[Hotez, Peter J.] Baylor Coll Med, Sabin Vaccine Inst, Houston, TX 77030 USA.
[Hotez, Peter J.] Baylor Coll Med, Texas Childrens Hosp, Ctr Vaccine Dev, Houston, TX 77030 USA.
[Pennington, Michael W.] Peptides Int, Louisville, KY USA.
NR 0
TC 0
Z9 0
U1 1
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 739A
EP 739A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000404193
ER
PT J
AU Papp, F
Babikow, E
Smith, J
Chang, TH
Swartz, KJ
AF Papp, Ferenc
Babikow, Erika
Smith, Jaime
Chang, Tsg-Hui
Swartz, Kenton J.
TI Exploring Conformational Rearrangements in a Novel Voltage-Sensing
Protein
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Papp, Ferenc; Babikow, Erika; Smith, Jaime; Chang, Tsg-Hui; Swartz, Kenton J.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 745A
EP 745A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000404221
ER
PT J
AU Hoogerheide, DP
Vaish, A
Rostovtseva, T
Kuszak, A
Bezrukov, S
Krueger, S
Nanda, H
AF Hoogerheide, David P.
Vaish, Amit
Rostovtseva, Tatiana
Kuszak, Adam
Bezrukov, Sergey
Krueger, Susan
Nanda, Hirsh
TI Towards the Incorporation of Functional Ion Channel Proteins in Tethered
Membranes
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Hoogerheide, David P.; Vaish, Amit; Krueger, Susan; Nanda, Hirsh] NIST, Ctr Neutron Res, Gaithersburg, MD 20899 USA.
[Hoogerheide, David P.; Rostovtseva, Tatiana; Bezrukov, Sergey] NICHHD, NIH, Bethesda, MD 20892 USA.
[Kuszak, Adam] NIDDK, NIH, Bethesda, MD 20892 USA.
[Nanda, Hirsh] Carnegie Mellon Univ, Dept Phys, Pittsburgh, PA 15213 USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 746A
EP 746A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000404227
ER
PT J
AU Jara-Oseguera, A
Bae, C
Zhang, F
Chang, TH
Kim, JI
Swartz, KJ
AF Jara-Oseguera, Andres
Bae, Chanhyung
Zhang, Feng
Chang, Tsg-Hui
Kim, Jae Il
Swartz, Kenton J.
TI Exploring the Architecture of the Outer Pore of the TRPV1 Channel with
Double-Knot Toxin
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Jara-Oseguera, Andres; Bae, Chanhyung; Zhang, Feng; Chang, Tsg-Hui; Swartz, Kenton J.] NINDS, Bethesda, MD 20892 USA.
[Kim, Jae Il] Gwangju Inst Sci & Technol GIST, Sch Life Sci, Kwangju, South Korea.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 755A
EP 755A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000404274
ER
PT J
AU Hanson, SM
Newstead, S
Swartz, KJ
Sansom, MSP
AF Hanson, Sonya M.
Newstead, Simon
Swartz, Kenton J.
Sansom, Mark S. P.
TI Toward the Mechanism of Capsaicin Binding to TRPV1 in a Lipid Bilayer
via Atomistic Simulation
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Hanson, Sonya M.; Swartz, Kenton J.] NINDS, NIH, Bethesda, MD 20892 USA.
[Hanson, Sonya M.; Newstead, Simon; Sansom, Mark S. P.] Univ Oxford, Dept Biochem, Oxford OX1 3QU, England.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 756A
EP 756A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000404276
ER
PT J
AU Islas, LD
Jara-Oseguera, A
AF Islas, Leon D.
Jara-Oseguera, Andres
TI Allosteric Coupling and Thermal Activation in TRP Channels
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Islas, Leon D.] Univ Nacl Autonoma Mexico, Sch Med, Mexico City 04510, DF, Mexico.
[Jara-Oseguera, Andres] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 756A
EP 756A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000404275
ER
PT J
AU Bae, C
Krepkiy, DV
Kalia, J
Kim, J
Kim, JI
Swartz, KJ
AF Bae, Chanhyung
Krepkiy, Dmitriy V.
Kalia, Jeet
Kim, Jaehyun
Kim, Jae Il
Swartz, Kenton J.
TI Structural Characterization of Double-Knot Toxin, an Activator of TRPV1
Channels
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Bae, Chanhyung; Krepkiy, Dmitriy V.; Kalia, Jeet; Swartz, Kenton J.] NIH, Bethesda, MD 20892 USA.
[Kim, Jaehyun; Kim, Jae Il] GIST, Kwangju, South Korea.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 757A
EP 757A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000404282
ER
PT J
AU Szatmary, AC
AF Szatmary, Alex C.
TI Neutrophil Rolling on Patches of Selectin
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Szatmary, Alex C.] NICHD, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 789A
EP 789A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000404436
ER
PT J
AU Liu, HY
Sept, D
Kapoor, K
Ambudkar, SV
Mayer, M
AF Liu, Haiyan
Sept, David
Kapoor, Khyati
Ambudkar, Suresh V.
Mayer, Michael
TI Functional Assay for Characterizing Human P-Glycoprotein Transport using
the Pore Forming Peptide Gramicidin A
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Liu, Haiyan; Sept, David; Mayer, Michael] Univ Michigan, Dept Biomed Engn, Ann Arbor, MI 48109 USA.
[Kapoor, Khyati; Ambudkar, Suresh V.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RI Mayer, Michael/C-1299-2010
OI Mayer, Michael/0000-0002-6148-5756
NR 0
TC 0
Z9 0
U1 0
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 791A
EP 791A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000404444
ER
PT J
AU Bumb, A
Sarkar, SK
Wu, XF
Sochacki, KA
Kellman, P
Brechbiel, MW
Neuman, KC
AF Bumb, Ambika
Sarkar, Susanta K.
Wu, Xufeng
Sochacki, Kem A.
Kellman, Peter
Brechbiel, Martin W.
Neuman, Keir C.
TI Wide-Field Background Free Imaging by Magnetic Modulation of Nanodiamond
Fluorescence
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Bumb, Ambika; Sarkar, Susanta K.; Neuman, Keir C.] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA.
[Wu, Xufeng] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA.
[Sochacki, Kem A.] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA.
[Kellman, Peter] NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA.
[Brechbiel, Martin W.] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
RI Neuman, Keir/F-7400-2011
OI Neuman, Keir/0000-0002-0863-5671
NR 0
TC 0
Z9 0
U1 3
U2 11
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 796A
EP 796A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000404472
ER
PT J
AU Beaven, AH
Sodt, AJ
Greathouse, DV
Koeppe, RE
Pastor, RW
Andersen, OS
Im, W
AF Beaven, Andrew H.
Sodt, Alexander J.
Greathouse, Denise V.
Koeppe, Roger E., II
Pastor, Richard W.
Andersen, Olaf S.
Im, Wonpil
TI All-Atom Simulation and Continuum Elastic Theory of Gramicidin a in
Binary Component Lipid Bilayers
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Beaven, Andrew H.] Univ Kansas, Lawrence, KS 66045 USA.
[Sodt, Alexander J.; Pastor, Richard W.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA.
[Greathouse, Denise V.; Koeppe, Roger E., II] Univ Arkansas, Fayetteville, AR 72701 USA.
[Andersen, Olaf S.] Weill Cornell Med Coll, New York, NY USA.
[Im, Wonpil] Univ Kansas, Lawrence, KS 66045 USA.
[Im, Wonpil] Univ Kansas, Ctr Bioinformat, Lawrence, KS 66045 USA.
NR 0
TC 0
Z9 0
U1 0
U2 7
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 801A
EP 801A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000404493
ER
PT J
AU Belcher, J
Yao, YN
Berger, AJ
Mayer, ML
Lau, A
AF Belcher, John
Yao, Yongneng
Berger, Anthony J.
Mayer, Mark L.
Lau, Albert
TI Principal Component Analysis of Glutamate Receptor Ligand Binding
Domains
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 58th Annual Meeting of the Biophysical-Society
CY FEB 15-19, 2014
CL San Francisco, CA
SP Biophys Soc
C1 [Belcher, John; Lau, Albert] Johns Hopkins Sch Med, Baltimore, MD USA.
[Yao, Yongneng] Columbia Univ, New York, NY USA.
[Berger, Anthony J.] Univ Wisconsin, Madison, WI USA.
[Mayer, Mark L.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 28
PY 2014
VL 106
IS 2
SU 1
BP 805A
EP 805A
PG 1
WC Biophysics
SC Biophysics
GA AI6QE
UT WOS:000337000404515
ER
PT J
AU Zonderman, AB
Dore, GA
AF Zonderman, Alan B.
Dore, Gregory A.
TI Risk of dementia after fluctuating mild cognitive impairment
SO NEUROLOGY
LA English
DT Editorial Material
AB Friends, family members, and medical caretakers notice that sometimes we have good days and sometimes we have bad days. If we are older, the bad days may involve making poor judgments, acting impulsively, forgetting information we just heard, or repeating ourselves in conversations. If these oscillations persist, then someone we know well may suggest consulting a physician because our bad days are interfering with our daily activities. Presented with variable symptoms on different occasions, physicians legitimately may diagnose us with mild cognitive impairment (MCI) on one occasion and then equally legitimately retract the diagnosis on another occasion. Many in the field have observed that patients and study participants may yo-yo between normal cognitive performance and MCI, but until now, the import of these diagnostic fluctuations was unclear.
C1 [Zonderman, Alan B.; Dore, Gregory A.] NIA, Behav Epidemiol Sect, Lab Epidemiol & Populat Sci, Biomed Res Ctr,Intramural Res Program, Baltimore, MD USA.
RP Zonderman, AB (reprint author), NIA, Behav Epidemiol Sect, Lab Epidemiol & Populat Sci, Biomed Res Ctr,Intramural Res Program, Baltimore, MD USA.
EM zondermana@mail.nih.gov
OI Zonderman, Alan B/0000-0002-6523-4778
NR 4
TC 2
Z9 2
U1 1
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 JAN 28
PY 2014
VL 82
IS 4
BP 290
EP 291
DI 10.1212/WNL.0000000000000065
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA AH2YZ
UT WOS:000335989500007
PM 24353338
ER
PT J
AU Goldberger, JJ
Basu, A
Boineau, R
Buxton, AE
Cain, ME
Canty, JM
Chen, PS
Chugh, SS
Costantini, O
Exner, DV
Kadish, AH
Lee, B
Lloyd-Jones, D
Moss, AJ
Myerburg, RJ
Olgin, JE
Passman, R
Stevenson, WG
Tomaselli, GF
Zareba, W
Zipes, DP
Zoloth, L
AF Goldberger, Jeffrey J.
Basu, Anirban
Boineau, Robin
Buxton, Alfred E.
Cain, Michael E.
Canty, John M., Jr.
Chen, Peng-Sheng
Chugh, Sumeet S.
Costantini, Otto
Exner, Derek V.
Kadish, Alan H.
Lee, Byron
Lloyd-Jones, Donald
Moss, Arthur J.
Myerburg, Robert J.
Olgin, Jeffrey E.
Passman, Rod
Stevenson, William G.
Tomaselli, Gordon F.
Zareba, Wojciech
Zipes, Douglas P.
Zoloth, Laurie
TI Risk Stratification for Sudden Cardiac Death A Plan for the Future
SO CIRCULATION
LA English
DT Article
ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; ACUTE MYOCARDIAL-INFARCTION;
C-REACTIVE PROTEIN; LEFT-VENTRICULAR DYSFUNCTION;
CORONARY-ARTERY-DISEASE; IDIOPATHIC DILATED CARDIOMYOPATHY;
MULTIPLE-SOURCE SURVEILLANCE; BLOOD-INSTITUTE WORKSHOP; GENOME-WIDE
ASSOCIATION; QT INTERVAL DURATION
C1 [Goldberger, Jeffrey J.; Kadish, Alan H.; Passman, Rod] Northwestern Univ, Dept Med Cardiol, Chicago, IL 60611 USA.
[Lloyd-Jones, Donald; Passman, Rod] Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA.
[Zoloth, Laurie] Northwestern Univ, Weinberg Coll Arts & Sci & Med Humanities & Bioet, Chicago, IL 60611 USA.
[Basu, Anirban] Univ Washington, Dept Hlth Serv & Pharm, Seattle, WA 98195 USA.
[Boineau, Robin] NIH, Washington, DC USA.
[Buxton, Alfred E.] Beth Israel Deaconess Med Ctr, Cardiovasc Inst, Boston, MA 02215 USA.
[Cain, Michael E.; Canty, John M., Jr.] SUNY Buffalo, Dept Med, Buffalo, NY 14260 USA.
[Chen, Peng-Sheng; Zipes, Douglas P.] Indiana Univ, Krannert Inst Cardiol, Indianapolis, IN USA.
[Chugh, Sumeet S.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
[Costantini, Otto] Summa Hlth Syst Cardiovasc Inst, Cleveland, OH USA.
[Exner, Derek V.] CON ECT Clin Coordinating Ctr, Calgary, AB, Canada.
[Lee, Byron; Olgin, Jeffrey E.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Moss, Arthur J.] Univ Rochester, Med Ctr, Dept Med, Rochester, NY 14642 USA.
[Zareba, Wojciech] Univ Rochester, Med Ctr, Dept Med Cardiol, Rochester, NY 14642 USA.
[Myerburg, Robert J.] Univ Miami Hlth Syst, Dept Med, Miami, FL USA.
[Stevenson, William G.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Tomaselli, Gordon F.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA.
RP Goldberger, JJ (reprint author), Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, 645 N Michigan Ave,Ste 1006, Chicago, IL 60611 USA.
EM j-goldberger@northwestern.edu
FU Boston Scientific; Medtronic; St. Jude Medical
FX The Path to Improved Risk Stratification, NFP is a not-for-profit think
tank and has received unrestricted educational grants from Boston
Scientific, Medtronic, and St. Jude Medical.
NR 97
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U1 2
U2 13
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 JAN 28
PY 2014
VL 129
IS 4
BP 516
EP 526
PG 11
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA AA8OK
UT WOS:000331354600017
PM 24470473
ER
PT J
AU Kapetanovic, S
Griner, R
Zeldow, B
Nichols, S
Leister, E
Gelbard, HA
Miller, TL
Hazra, R
Mendez, AJ
Malee, K
Kammerer, B
Williams, PL
AF Kapetanovic, Suad
Griner, Ray
Zeldow, Bret
Nichols, Sharon
Leister, Erin
Gelbard, Harris A.
Miller, Tracie L.
Hazra, Rohan
Mendez, Armando J.
Malee, Kathleen
Kammerer, Betsy
Williams, Paige L.
CA Pediat HIV AIDS Cohort Study Team
TI Biomarkers and neurodevelopment in perinatally HIV-infected or exposed
youth: a structural equation model analysis
SO AIDS
LA English
DT Article
DE HIV-affected children; inflammatory markers; neurodevelopmental
outcomes; perinatal HIV infection
ID VASCULAR DYSFUNCTION; CHILDREN; MARKERS; BRAIN; INFLAMMATION;
ABNORMALITIES; ACTIVATION; CYTOKINE; MOTHERS; PROTEIN
AB Objective:To examine the relationship between markers of vascular dysfunction and neurodevelopmental outcomes in perinatally HIV-infected (PHIV+) and perinatally HIV-exposed but uninfected (PHEU) youth.Design:Cross-sectional design within a prospective, 15-site US-based cohort study.Methods:Neurodevelopmental outcomes were evaluated in relation to nine selected vascular biomarkers in 342 youth (212 PHIV+, 130 PHEU). Serum levels were assessed for adiponectin, C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), soluble vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sE-selectin), monocyte chemoattractant protein (sMCP-1), intercellular adhesion molecule-1 (sICAM-1), and P-selectin (sP-selectin). The Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) was administered at entry, yielding a Full-Scale IQ score, and four index scores. Factor analysis was conducted to reduce the biomarkers to fewer factors with related biological roles. Structural equation models (SEMs) were used to measure associations between resulting factors and WISC-IV scores.Results:Mean participant age was 11.4 years, 54% were female, 70% black. The nine biomarkers were clustered into three factor groups: F1 (fibrinogen, CRP, and IL-6); F2 (sICAM-1 and sVCAM-1); and F3 (MCP-1, sP-selectin, and sE-selectin). Adiponectin showed little correlation with any factor. SEMs revealed significant negative association of F1 with WISC-IV processing speed score in the total cohort. This effect remained significant after adjusting for HIV status and other potential confounders. A similar association was observed when restricted to PHIV+ participants in both unadjusted and adjusted SEMs.Conclusion:Aggregate measures of fibrinogen, CRP, and IL-6 may serve as a latent biomarker associated with relatively decreased processing speed in both PHIV+ and PHEU youth. (C) 2014 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
C1 [Kapetanovic, Suad] NIMH, NIH, Bethesda, MD 20892 USA.
[Griner, Ray; Zeldow, Bret; Leister, Erin; Williams, Paige L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Nichols, Sharon] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA.
[Gelbard, Harris A.] Univ Rochester, Med Ctr, Ctr Neural Dev & Dis, Rochester, NY 14642 USA.
[Miller, Tracie L.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
[Hazra, Rohan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Mendez, Armando J.] Univ Miami, Miller Sch Med, Div Endocrinol Diabet & Metab, Dept Med, Miami, FL 33136 USA.
[Malee, Kathleen] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Kammerer, Betsy] Boston Childrens Hosp, Dept Psychiat, Boston, MA USA.
RP Kapetanovic, S (reprint author), NIMH, NIH, Off Clin Director, Bldg 10-CRC,Room 6-5340,10 Ctr Dr, Bethesda, MD 20892 USA.
EM suad.kapetanovic@nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; National Institute of Allergy and Infectious Diseases;
National Institute on Drug Abuse; National Institute of Mental Health;
National Institute of Deafness and Other Communication Disorders;
National Heart Lung and Blood Institute; National Institute of
Neurological Disorders and Stroke; National Institute on Alcohol Abuse
and Alcoholism; Harvard University School of Public Health [U01
HD052102-04]; Tulane University School of Medicine [U01 HD052104-01]
FX The study was supported by the Eunice Kennedy Shriver National Institute
of Child Health and Human Development with co-funding from the National
Institute of Allergy and Infectious Diseases, the National Institute on
Drug Abuse, the National Institute of Mental Health, the National
Institute of Deafness and Other Communication Disorders, the National
Heart Lung and Blood Institute, National Institute of Neurological
Disorders and Stroke, and the National Institute on Alcohol Abuse and
Alcoholism, through cooperative agreements with the Harvard University
School of Public Health (U01 HD052102-04) (Principal Investigator:
George R. Seage, III; Project Director: Julie Alperen) and the Tulane
University School of Medicine (U01 HD052104-01) (Principal Investigator:
Russell B. Van Dyke; Co-Principal Investigator: Kenneth Rich; Project
Director: Patrick Davis). Data management services were provided by
Frontier Science and Technology Research Foundation (PI: Suzanne
Siminski), and regulatory services and logistical support were provided
by Westat, Inc. (PI: Mercy Swatson).
NR 37
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U1 2
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
EI 1473-5571
J9 AIDS
JI Aids
PD JAN 28
PY 2014
VL 28
IS 3
BP 355
EP 364
DI 10.1097/QAD.0000000000000072
PG 10
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA AB1OA
UT WOS:000331560500008
PM 24670521
ER
PT J
AU Uldrick, TS
Pipkin, S
Scheer, S
Hessol, NA
AF Uldrick, Thomas S.
Pipkin, Sharon
Scheer, Susan
Hessol, Nancy A.
TI Factors associated with survival among patients with AIDS-related
primary central nervous system lymphoma
SO AIDS
LA English
DT Article
DE AIDS; AIDS-related lymphoma; brain neoplasms; HAART; prognosis; risk
factors; time factors
ID ACTIVE ANTIRETROVIRAL THERAPY; ACQUIRED-IMMUNODEFICIENCY-SYNDROME;
PRIMARY CNS LYMPHOMA; NON-HODGKINS-LYMPHOMA; EPSTEIN-BARR-VIRUS;
HIV-INFECTION; UNITED-STATES; NATURAL-HISTORY; FLOW-CYTOMETRY;
SAN-FRANCISCO
AB Objective:AIDS-related primary central nervous system lymphoma (AR-PCNSL) has a poor prognosis. Improved understanding of specific patient, infectious, diagnostic, and treatment-related factors that affect overall survival (OS) is required to improve outcomes.Design:Population-based registry linkage study.Methods:Adult cases from the San Francisco AIDS registry (1990-2000) were matched with the California Cancer Registry (1985-2002) to ascertain AR-PCNSL data. Survival time was assessed through 31 December 2007. Risk factors and temporal trends for death were measured using two-sided Kaplan-Meier and Cox analyses.Results:Two hundred and seven AR-PCNSL patients were identified: 68% were white, 20% Hispanic, 10% African-American, and 2% Asian. Nineteen percent of patients had central nervous system (CNS) opportunistic infections diagnosed prior to AR-PCNSL. Fifty-seven percent of patients received radiation and/or chemotherapy and 12% used HAART prior to or within 30 days of AR-PCNSL diagnosis. One hundred and ninety-nine patients died (34deaths/100 person-years). In adjusted analysis, prior CNS opportunistic infection diagnosis increased risk of death (hazard ratio 1.9, P=0.0006) whereas radiation and/or chemotherapy decreased risk (hazard ratio 0.6, P<0.0001). AR-PCNSL diagnosis 1999-2002 had a lower mortality risk (hazard ratio=0.4, P=0.02) compared to 1990-1995. African-Americans had an increased risk of death compared to whites or Asians (hazard ratio=2.0, P=0.007).Conclusion:OS among AR-PCNSL patients improved over time but remains poor, especially among African-Americans. Prospective evaluation of curative therapy in AR-PCNSL is urgently needed. Accurate diagnosis of CNS mass lesions in patients with AIDS is required and for those with AR-PCNSL, antiretroviral therapy with concomitant AR-PCNSL therapy, and antimicrobial supportive care may improve OS. (C) 2014 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
C1 [Uldrick, Thomas S.] NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Pipkin, Sharon; Scheer, Susan] Univ Calif San Francisco, San Francisco Dept Publ Hlth, San Francisco, CA 94143 USA.
[Hessol, Nancy A.] Univ Calif San Francisco, Dept Clin Pharm, San Francisco, CA 94143 USA.
[Hessol, Nancy A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
RP Uldrick, TS (reprint author), 10 Ctr Dr,Room 6N106,MSC 1868, Bethesda, MD 20892 USA.
EM uldrickts@mail.nih.gov
FU Centers for Disease Control and Prevention; National Institute of
Allergy and Infectious Diseases [RO3-AI055270]; National Cancer
Institute (NCI), NIH
FX Funding was provided by the Centers for Disease Control and Prevention
to conduct AIDS case surveillance and the National Institute of Allergy
and Infectious Diseases, Grant number RO3-AI055270. This research was
supported in part by the Intramural Research Program, National Cancer
Institute (NCI), NIH.
NR 58
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U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
EI 1473-5571
J9 AIDS
JI Aids
PD JAN 28
PY 2014
VL 28
IS 3
BP 397
EP 405
DI 10.1097/QAD.0000000000000030
PG 9
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA AB1OA
UT WOS:000331560500012
PM 24076659
ER
PT J
AU Zhelev, DV
Zheleva, TS
AF Zhelev, Doncho V.
Zheleva, Tsvetanka S.
TI Silver nanoplates with ground or metastable structures obtained from
template-free two-phase aqueous/organic synthesis
SO JOURNAL OF APPLIED PHYSICS
LA English
DT Article
ID ELECTRON-DIFFRACTION PATTERNS; HEXAGONAL STRUCTURE; CRYSTAL-STRUCTURE;
NANOSTRUCTURES; NANOWIRES; GROWTH; AG; NANOCRYSTALS; PROGRAM; GOLD
AB Silver has unique electrical, catalytic, and plasmonic characteristics and has been widely sought for fabrication of nanostructures. The properties of silver nanostructures are intimately coupled to the structure of silver crystals. Two crystal structures are known for silver: the stable (ground) state cubic face centered 3C-Ag structure and the metastable hexagonal 4H-Ag structure. Recently, Chackraborty et al. [J. Phys.: Condens. Matter 23, 325401 (2011)] discovered a low density, highly reactive metastable hexagonal 2H-Ag structure accessible during electrodeposition of silver nanowires in porous anodic alumina templates. This 2H-Ag structure has enhanced electrical and catalytic characteristics. In the present work we report template-free synthesis of silver nanoplates with the metastable 2H-Ag crystal structure, which appears together with the ground 3C-Ag and the metastable 4H-Ag structures in a two-phase solution synthesis with citric acid as the capping agent. The capacity of citric acid to stabilize both the stable and the metastable structures is explained by its preferential binding to the close packed facets of Ag crystals, which are the (111) planes for 3C-Ag and the (0001) planes for 4H-Ag and 2H-Ag. Nanoplate morphology and structure are characterized using scanning electron microscopy, X-ray diffraction, and transmission electron microscopy. The synthesized nanoplates have thickness from 15 to 17 nm and edge length from 1 to 10 mu m. Transmission electron microscopy selected area electron diffraction is used to uniquely identify and distinguish between nanoplates with 2H-Ag or 4H-Ag or 3C-Ag structures.
C1 [Zhelev, Doncho V.; Zheleva, Tsvetanka S.] Army Res Lab, Adelphi, MD 20783 USA.
RP Zhelev, DV (reprint author), NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA.
EM dontcho.jelev@nih.gov
FU Army Research Laboratory
FX D.V.Z. acknowledges the financial support from the Army Research
Laboratory. D.V.Z. is grateful to Dr. Paul Pellegrino for the
introduction to surface enhanced Raman spectroscopy.
NR 42
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Z9 2
U1 2
U2 36
PU AMER INST PHYSICS
PI MELVILLE
PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA
SN 0021-8979
EI 1089-7550
J9 J APPL PHYS
JI J. Appl. Phys.
PD JAN 28
PY 2014
VL 115
IS 4
AR 044309
DI 10.1063/1.4859497
PG 7
WC Physics, Applied
SC Physics
GA AA6LW
UT WOS:000331210800101
ER
PT J
AU Ren, XF
Park, SY
Bonifacino, JS
Hurley, JH
AF Ren, Xuefeng
Park, Sang Yoon
Bonifacino, Juan S.
Hurley, James H.
TI How HIV-1 Nef hijacks the AP-2 clathrin adaptor to downregulate CD4
SO ELIFE
LA English
DT Article
ID VIRUS TYPE-1 NEF; CELL-SURFACE CD4; DILEUCINE MOTIF; SH3 DOMAIN;
CYTOPLASMIC DOMAIN; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; BINDING
SURFACE; AP2 COMPLEX; PROTEIN
AB The Nef protein of HIV-1 downregulates the cell surface co-receptor CD4 by hijacking the clathrin adaptor complex AP-2. The structural basis for the hijacking of AP-2 by Nef is revealed by a 2.9 angstrom crystal structure of Nef bound to the a and sigma 2 subunits of AP-2. Nef binds to AP-2 via its central loop (residues 149-179) and its core. The determinants for Nef binding include residues that directly contact AP-2 and others that stabilize the binding-competent conformation of the central loop. Residues involved in both direct and indirect interactions are required for the binding of Nef to AP-2 and for downregulation of CD4. These results lead to a model for the docking of the full AP-2 tetramer to membranes as bound to Nef, such that the cytosolic tail of CD4 is situated to interact with its binding site on Nef.
C1 [Ren, Xuefeng; Hurley, James H.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
[Ren, Xuefeng; Hurley, James H.] Univ Calif Berkeley, Calif Inst Quantit Biosci, Berkeley, CA 94720 USA.
[Ren, Xuefeng; Park, Sang Yoon; Bonifacino, Juan S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD USA.
RP Bonifacino, JS (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD USA.
EM bonifacinoj@helix.nih.gov; jimhurley@berkeley.edu
FU National Institute of General Medical Sciences [P50GM082250]; Eunice
Kennedy Shriver National Institute of Child Health and Human Development
[HD001607-22]; Intramural AIDS Targeted Antiviral Program of the
National Institutes of Health
FX National Institute of General Medical Sciences P50GM082250 James H
Hurley; Eunice Kennedy Shriver National Institute of Child Health and
Human Development HD001607-22 Juan S Bonifacino; The Intramural AIDS
Targeted Antiviral Program of the National Institutes of Health Juan S
Bonifacino
NR 59
TC 25
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U1 0
U2 12
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD JAN 28
PY 2014
VL 3
AR e01754
DI 10.7554/eLife.01754
PG 19
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA AA5NF
UT WOS:000331145800008
PM 24473078
ER
PT J
AU Harmon, KJ
Bennett, EE
Gomella, AA
Wen, H
AF Harmon, Katherine J.
Bennett, Eric E.
Gomella, Andrew A.
Wen, Han
TI Efficient Decoding of 2D Structured Illumination with Linear Phase
Stepping in X-Ray Phase Contrast and Dark-Field Imaging
SO PLOS ONE
LA English
DT Article
ID 2-DIMENSIONAL GRATING INTERFEROMETER; SCATTER CORRECTION METHOD;
FRINGE-PATTERN ANALYSIS; FRESNEL ZONE-PLATE; WAVE-FRONT; PRIMARY
MODULATION; FOURIER-TRANSFORM; TOMOGRAPHY; CT
AB The ability to map the phase distribution and lateral coherence of an x-ray wavefront offers the potential for imaging the human body through phase contrast, without the need to deposit significant radiation energy. The classic means to achieve this goal is structured illumination, in which a periodic intensity modulation is introduced into the image, and changes in the phase distribution of the wavefront are detected as distortions of the modulation pattern. Two-dimensional periodic patterns are needed to fully characterize a transverse wavefront. Traditionally, the information in a 2D pattern is retrieved at high resolution by acquiring multiple images while shifting the pattern over a 2D matrix of positions. Here we describe a method to decode 2D periodic patterns with single-axis phase stepping, without either a loss of information or increasing the number of sampling steps. The method is created to reduce the instrumentation complexity of high-resolution 2D wavefront sensing in general. It is demonstrated with motionless electromagnetic phase stepping and a flexible processing algorithm in x-ray dark-field and phase contrast imaging.
C1 [Harmon, Katherine J.; Bennett, Eric E.; Gomella, Andrew A.; Wen, Han] NHLBI, Imaging Phys Lab, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA.
RP Wen, H (reprint author), NHLBI, Imaging Phys Lab, Biochem & Biophys Ctr, 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 of the National Heart, Lung and Blood
Institute, National Institutes of Health (NIH), part of the Health and
Human Services Department of the US Federal Government
FX The work is funded by the Division of Intramural Research of the
National Heart, Lung and Blood Institute, National Institutes of Health
(NIH), which is part of the Health and Human Services Department of the
US Federal Government. All authors are affiliated with NIH. The work is
performed as official duty in fulfilling the general mission of NIH. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 35
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U1 0
U2 11
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JAN 28
PY 2014
VL 9
IS 1
AR e87127
DI 10.1371/journal.pone.0087127
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 301CJ
UT WOS:000330510000110
PM 24489853
ER
PT J
AU Kwon, YD
LaLonde, JM
Yang, YP
Elban, MA
Sugawara, A
Courter, JR
Jones, DM
Smith, AB
Debnath, AK
Kwong, PD
AF Kwon, Young Do
LaLonde, Judith M.
Yang, Yongping
Elban, Mark A.
Sugawara, Akihiro
Courter, Joel R.
Jones, David M.
Smith, Amos B., III
Debnath, Asim K.
Kwong, Peter D.
TI Crystal Structures of HIV-1 gp120 Envelope Glycoprotein in Complex with
NBD Analogues That Target the CD4-Binding Site
SO PLOS ONE
LA English
DT Article
ID SMALL-MOLECULE INHIBITORS; STRUCTURE-BASED DESIGN; VIRUS TYPE-1 ENTRY;
CD4-MIMETIC MINIPROTEIN; ANTIVIRAL ACTIVITY; AIDS PATIENTS; HTLV-III;
X-RAY; RECEPTOR; CCR5
AB Efforts to develop therapeutic agents that inhibit HIV-1 entry have led to the identification of several small molecule leads. One of the most promising is the NBD series, which binds within a conserved gp120 cavity and possesses para-halogen substituted aromatic rings, a central oxalamide linker, and a tetramethylpiperidine moiety. In this study, we characterized structurally the interactions of four NBD analogues containing meta-fluoro substitution on the aromatic ring and various heterocyclic ring replacements of the tetramethylpiperidine group. The addition of a meta-fluorine to the aromatic ring improved surface complementarity and did not alter the position of the analogue relative to gp120. By contrast, heterocyclic ring replacements of the tetramethylpiperidine moiety exhibited diverse positioning and interactions with the vestibule of the gp120 cavity. Overall, the biological profile of NBD-congeners was modulated by ligand interactions with the gp120-cavity vestibule. Herein, six co-crystal structures of NBD-analogues with gp120 provide a structural framework for continued small molecule-entry inhibitor optimization.
C1 [Kwon, Young Do; Yang, Yongping; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[LaLonde, Judith M.] Bryn Mawr Coll, Dept Chem, Bryn Mawr, PA 19010 USA.
[Elban, Mark A.; Sugawara, Akihiro; Courter, Joel R.; Jones, David M.; Smith, Amos B., III] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA.
[Debnath, Asim K.] New York Blood Ctr, Lindsley F Kimball Res Inst, Lab Mol Modeling & Drug Design, New York, NY 10021 USA.
RP Kwong, PD (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM pdkwong@nih.gov
RI Kwon, Young Do/A-6957-2010;
OI Sugawara, Akihiro/0000-0003-1266-7497
FU Intramural AIDS Targeted Antiviral Program; Intramural Research Program
of the National Institutes of Health (NIH); NIH [GM 56550]; US
Department of Energy, Basic Energy Sciences, Office of Science
[W-31-109-Eng-38]
FX Support for this work was provided by the Intramural AIDS Targeted
Antiviral Program, by the Intramural Research Program of the National
Institutes of Health (NIH), and by NIH GM 56550 to JL and ABS. Use of
sector 22 (Southeast Region Collaborative Access team) at the Advanced
Photon Source was supported by the US Department of Energy, Basic Energy
Sciences, Office of Science, under contract number W-31-109-Eng-38. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 39
TC 13
Z9 14
U1 1
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 JAN 28
PY 2014
VL 9
IS 1
AR e85940
DI 10.1371/journal.pone.0085940
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 301CJ
UT WOS:000330510000025
PM 24489681
ER
PT J
AU Lui, JLC
Chen, WP
Cheung, CSF
Baron, J
AF Lui, Julian C.
Chen, Weiping
Cheung, Crystal S. F.
Baron, Jeffrey
TI Broad Shifts in Gene Expression during Early Postnatal Life Are
Associated with Shifts in Histone Methylation Patterns
SO PLOS ONE
LA English
DT Article
ID EMBRYONIC STEM-CELLS; TRANSCRIPTOME ANALYSIS; CHROMATIN STATE; GENOME;
DIFFERENTIATION; REVEALS; H3K4ME3; DISEASE; LISTS; CHIP
AB During early postnatal life, extensive changes in gene expression occur concomitantly in multiple major organs, indicating the existence of a common core developmental genetic program. This program includes hundreds of growth-promoting genes that are downregulated with age in liver, kidney, lung, and heart, and there is evidence that this component of the program drives the widespread decline in cell proliferation that occurs in juvenile life, as organs approach adult sizes. To investigate epigenetic changes that might orchestrate this program, we performed chromatin immunoprecipitation-promoter tiling array to assess temporal changes in histone H3K4 and H3K27 trimethylation (me3) at promoter regions throughout the genome in kidney and lung, comparing 1- to 4-wk-old mice. We found extensive genome-wide shifts in H3K4me3 and H3K27me3 occurring with age in both kidney and lung. The number of genes with concordant changes in the two organs was far greater than expected by chance. Temporal changes in H3K4me3 showed a strong, positive association with changes in gene expression, assessed by microarray, whereas changes in H3K27me3 showed a negative association. Gene ontology analysis indicated that shifts in specific histone methylation marks were associated with specific developmental functions. Of particular interest, genes with decreases in H3K4me3 with age in both organs were strongly implicated in cell cycle and cell proliferation functions. Taken together, the findings suggest that the common core developmental program of gene expression which occurs in multiple organs during juvenile life is associated with a common core developmental program of histone methylation. In particular, declining H3K4me3 is strongly associated with gene downregulation and occurs in the promoter regions of many growth-regulating genes, suggesting that this change in histone methylation may contribute to the component of the genetic program that drives juvenile body growth deceleration.
C1 [Lui, Julian C.; Cheung, Crystal S. F.; Baron, Jeffrey] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Dev, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
[Chen, Weiping] NIDDK, Microarray Core Facil, NIH, Bethesda, MD 20892 USA.
RP Lui, JLC (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Dev, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
EM luichunk@mail.nih.gov
RI Lui, Chun Kin Julian/E-2253-2012
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD), NIH
FX This work was supported by the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human Development
(NICHD), NIH. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 31
TC 5
Z9 5
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JAN 28
PY 2014
VL 9
IS 1
AR e86957
DI 10.1371/journal.pone.0086957
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 301CJ
UT WOS:000330510000093
PM 24489814
ER
PT J
AU Horton, BM
Hudson, WH
Ortlund, EA
Shirk, S
Thomas, JW
Young, ER
Zinzow-Kramer, WM
Maney, DL
AF Horton, Brent M.
Hudson, William H.
Ortlund, Eric A.
Shirk, Sandra
Thomas, James W.
Young, Emily R.
Zinzow-Kramer, Wendy M.
Maney, Donna L.
TI Estrogen receptor alpha polymorphism in a species with alternative
behavioral phenotypes
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE estradiol; testosterone; morph; reproductive tactics
ID WHITE-THROATED SPARROW; HISTORY TRADE-OFFS; ZONOTRICHIA-ALBICOLLIS;
SOCIAL-BEHAVIOR; CHROMOSOMAL-POLYMORPHISM; ELECTRICAL STIMULATION;
INDIVIDUAL-DIFFERENCES; SOCIOSEXUAL BEHAVIOR; SEXUAL-BEHAVIOR;
BREAST-CANCER
AB The evolution of behavior relies on changes at the level of the genome; yet the ability to attribute a behavioral change to a specific, naturally occurring genetic change is rare in vertebrates. In the white-throated sparrow (Zonotrichia albicollis), a chromosomal polymorphism (ZAL2/2(m)) is known to segregate with a behavioral phenotype. Individuals with the ZAL2(m) haplotype engage in more territorial aggression and less parental behavior than individuals without it. These behaviors are thought to be mediated by sensitivity to sex steroids, and the chromosomal rearrangement underlying the polymorphism has captured a prime candidate gene: estrogen receptor 1 (ESR1), which encodes estrogen receptor alpha (ER alpha). We therefore hypothesized that the behavioral effects of the ZAL2(m) rearrangement are mediated by polymorphism in ESR1. We report here that (i) the ESR1 promoter region contains fixed polymorphisms distinguishing the ZAL2(m) and ZAL2 alleles; (ii); those polymorphisms regulate transcription efficiency in vitro and therefore potentially do the same in vivo (iii); the local expression of ERa in the brain depends strongly on genotype in a free-living population; and (iv) ER alpha expression in the medial amygdala and medial preoptic area may fully mediate the effects of genotype on territorial aggression and parenting, respectively. Thus, our study provides a rare glimpse of how a chromosomal polymorphism has affected the brain and social behavior in a vertebrate. Our results suggest that in this species, differentiation of ESR1 has played a causal role in the evolution of phenotypes with alternative life- history strategies.
C1 [Horton, Brent M.; Shirk, Sandra; Zinzow-Kramer, Wendy M.; Maney, Donna L.] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA.
[Hudson, William H.; Ortlund, Eric A.] Emory Univ, Sch Med, Dept Biochem, Atlanta, GA 30322 USA.
[Thomas, James W.] NHGRI, NIH Intramural Sequencing Ctr, NIH, Rockville, MD 20852 USA.
[Young, Emily R.] Georgia Inst Technol, Dept Biol, Atlanta, GA 30332 USA.
RP Maney, DL (reprint author), Emory Univ, Dept Psychol, Atlanta, GA 30322 USA.
EM dmaney@emory.edu
RI Ortlund, Eric/F-4672-2014; Hudson, William/E-6622-2012; Maney,
Donna/G-3706-2011
OI Hudson, William/0000-0002-2513-1213;
FU National Institutes of Health (NIH) [1R01MH082833]; National Science
Foundation (NSF) [IOS- 0723805]; NIH [1R01DK095750, R21MH090418,
5T32GM008602]; American Heart Association [13PRE16920012]; NSF
[SMA-1306132]; National Human Genome Research Institute Intramural
Research program at the NIH
FX We thank D. Abebe, G. Bhat, J. Davis, C. Horoszko, O. Laur (Emory
University Custom Cloning Core Facility), C. Leung, J. Liang, and C.
MacDowell for technical assistance in Atlanta; A. Annis, E. Burns, J.
Cava, A. Cornell, C. Gurguis, J. Michaud, and C. McKee for field
assistance in Maine; C. Henry for access to freezer space and other
resources at the University of Maine; the Forest Society of Maine and J.
Metzler for permission to conduct our field study at the Hemlock Stream
Forest; P. Wolff and I. Waldman for advice on statistical methods; I.
Moore for the use of radioimmunoassay facilities; and the Departments of
Biology at Emory University and University of Maine for the use of
shared resources. This research was funded by National Institutes of
Health (NIH) Grant 1R01MH082833 and National Science Foundation (NSF)
Grant IOS- 0723805 (to D.L.M.), NIH Grant 1R01DK095750 (to E.A.O.), NIH
Grant R21MH090418 (to J.W.T.), NIH Grant 5T32GM008602 and American Heart
Association Grant 13PRE16920012 (to W.H.H.), and NSF Grant SMA-1306132
(to W.M.Z.-K.). J.W.T. was supported by the National Human Genome
Research Institute Intramural Research program at the NIH.
NR 48
TC 19
Z9 19
U1 7
U2 38
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 JAN 28
PY 2014
VL 111
IS 4
BP 1443
EP 1448
DI 10.1073/pnas.1317165111
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 297BV
UT WOS:000330231100057
PM 24474771
ER
PT J
AU Seo, K
Rainer, PP
Hahn, VS
Lee, DI
Jo, SH
Andersen, A
Liu, T
Xu, XP
Willette, RN
Lepore, JJ
Marino, JP
Birnbaumer, L
Schnackenberg, CG
Kass, DA
AF Seo, Kinya
Rainer, Peter P.
Hahn, Virginia Shalkey
Lee, Dong-ik
Jo, Su-Hyun
Andersen, Asger
Liu, Ting
Xu, Xiaoping
Willette, Robert N.
Lepore, John J.
Marino, Joseph P., Jr.
Birnbaumer, Lutz
Schnackenberg, Christine G.
Kass, David A.
TI Combined TRPC3 and TRPC6 blockade by selective small-molecule or genetic
deletion inhibits pathological cardiac hypertrophy
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE ion channels; calcium; nuclear factor of activated T cells; myocardial;
Gq-coupled protein receptors
ID CA2+ CHANNELS; CONTRIBUTES; ACTIVATION; HEART; IDENTIFICATION;
MECHANISM; CALCIUM; FAILURE; INFLUX; ENTRY
AB Chronic neurohormonal and mechanical stresses are central features of heart disease. Increasing evidence supports a role for the transient receptor potential canonical channels TRPC3 and TRPC6 in this pathophysiology. Channel expression for both is normally very low but is increased by cardiac disease, and genetic gain-or loss-of-function studies support contributions to hypertrophy and dysfunction. Selective small-molecule inhibitors remain scarce, and none target both channels, which may be useful given the high homology among them and evidence of redundant signaling. Here we tested selective TRPC3/6 antagonists (GSK2332255B and GSK2833503A; IC50, 3-21 nM against TRPC3 and TRPC6) and found dose-dependent blockade of cell hypertrophy signaling triggered by angiotensin II or endothelin-1 in HEK293T cells aswell as in neonatal and adult cardiac myocytes. In vivo efficacy in mice and rats was greatly limited by rapid metabolism and high protein binding, although antifibrotic effects with pressure overload were observed. Intriguingly, although gene deletion of TRPC3 or TRPC6 alone did not protect against hypertrophy or dysfunction from pressure overload, combined deletion was protective, supporting the value of dual inhibition. Further development of this pharmaceutical class may yield a useful therapeutic agent for heart disease management.
C1 [Seo, Kinya; Rainer, Peter P.; Hahn, Virginia Shalkey; Lee, Dong-ik; Jo, Su-Hyun; Liu, Ting; Kass, David A.] Johns Hopkins Med Inst, Dept Med, Div Cardiol, Baltimore, MD 21205 USA.
[Rainer, Peter P.] Med Univ Graz, Dept Med, Div Cardiol, A-8036 Graz, Austria.
[Jo, Su-Hyun] Kangwon Natl Univ, Sch Med, Dept Physiol, Inst Biosci & Biotechnol, Chunchon 200701, South Korea.
[Andersen, Asger] Aarhus Univ Hosp, Dept Cardiol, DK-8200 Aarhus, Denmark.
[Xu, Xiaoping; Willette, Robert N.; Lepore, John J.; Marino, Joseph P., Jr.; Schnackenberg, Christine G.] GlaxoSmithKline Heart Failure Discovery Performan, King Of Prussia, PA 19406 USA.
[Birnbaumer, Lutz] Natl Inst Environm Hlth Sci, Neurobiol Lab, Res Triangle Pk, NC 27709 USA.
RP Kass, DA (reprint author), Johns Hopkins Med Inst, Dept Med, Div Cardiol, Baltimore, MD 21205 USA.
EM dkass@jhmi.edu
RI Rainer, Peter/M-2145-2016
OI Rainer, Peter/0000-0002-2840-6454
FU GlaxoSmithKline; American Heart Association; Sarnoff Cardiovascular
Research Foundation; Austrian Academy of Sciences; National Research
Foundation of Korea [2011-0013171]; Danish Council for Independent
Research [11-108410]; National Institutes of Health [Z01-ES-101864,
HL089297, HL059408]; Muscular Dystrophy Association [186454]; Abraham
and Virginia Weiss Professorship; Peter Belfer Endowment
FX We thank Djahida Bedja (Johns Hopkins University) for technical
assistance. This work was supported by a grant from GlaxoSmithKline.
Additional funding was provided by an American Heart Association
MidAtlantic Fellowship Grant (to K.S. and D.- i.L.), a Research
Fellowship from the Sarnoff Cardiovascular Research Foundation (to V.S.
H.), a Max Kade Fellowship from the Austrian Academy of Sciences (to
P.P.R.), the National Research Foundation of Korea (Grant 2011-0013171,
to S.- H.J.), the Danish Council for Independent Research (Grant
11-108410, to A.A.), the Intramural Research Program of the National
Institutes of Health (Project Z01-ES-101864, to L.B.), National
Institutes of Health Grants HL089297 and HL059408, Muscular Dystrophy
Association Grant 186454, an Abraham and Virginia Weiss Professorship,
and the Peter Belfer Endowment (D.A.K.).
NR 37
TC 32
Z9 34
U1 1
U2 15
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 JAN 28
PY 2014
VL 111
IS 4
BP 1551
EP 1556
DI 10.1073/pnas.1308963111
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 297BV
UT WOS:000330231100075
PM 24453217
ER
PT J
AU Raznahan, A
Shaw, PW
Lerch, JP
Clasen, LS
Greenstein, D
Berman, R
Pipitone, J
Chakravarty, MM
Giedd, JN
AF Raznahan, Armin
Shaw, Phillip W.
Lerch, Jason P.
Clasen, Liv S.
Greenstein, Deanna
Berman, Rebecca
Pipitone, Jon
Chakravarty, Mallar M.
Giedd, Jay N.
TI Longitudinal four-dimensional mapping of subcortical anatomy in human
development
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID POSTERIOR PARIETAL CORTEX; BASAL GANGLIA; BRAIN-DEVELOPMENT; MACAQUE
MONKEYS; RHESUS-MONKEY; CORTICAL PROJECTIONS; MEDIODORSAL NUCLEUS;
WARPING TECHNIQUES; VENTRAL STRIATUM; PUBERTAL CHANGES
AB Growing access to large-scale longitudinal structural neuroimaging data has fundamentally altered our understanding of cortical development en route to human adulthood, with consequences for basic science, medicine, and public policy. In striking contrast, basic anatomical development of subcortical structures such as the striatum, pallidum, and thalamus has remained poorly described-despite these evolutionarily ancient structures being both intimate working partners of the cortical sheet and critical to diverse developmentally emergent skills and disorders. Here, to begin addressing this disparity, we apply methods for the measurement of subcortical volume and shape to 1,171 longitudinally acquired structural magnetic resonance imaging brain scans from 618 typically developing males and females aged 5-25 y. We show that the striatum, pallidum, and thalamus each follow curvilinear trajectories of volume change, which, for the striatum and thalamus, peak after cortical volume has already begun to decline and show a relative delay in males. Four-dimensional mapping of subcortical shape reveals that (i) striatal, pallidal, and thalamic domains linked to specific fronto-parietal association cortices contract with age whereas other subcortical territories expand, and (ii) each structure harbors hotspots of sexually dimorphic change over adolescence-with relevance for sex-biased mental disorders emerging in youth. By establishing the developmental dynamism, spatial heterochonicity, and sexual dimorphism of human subcortical maturation, these data bring our spatiotemporal understanding of subcortical development closer to that of the cortex-allowing evolutionary, basic, and clinical neuroscience to be conducted within a more comprehensive developmental framework.
C1 [Raznahan, Armin; Clasen, Liv S.; Greenstein, Deanna; Berman, Rebecca; Giedd, Jay N.] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA.
[Shaw, Phillip W.] NHGRI, Neurobehav Clin Res Sect, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA.
[Lerch, Jason P.; Chakravarty, Mallar M.] Ctr Addict & Mental Hlth, Kimel Family Imaging Genet Res Lab, Toronto, ON M5T 1R8, Canada.
[Pipitone, Jon; Chakravarty, Mallar M.] Univ Toronto, Dept Psychiat, Toronto, ON M5T 1R8, Canada.
[Pipitone, Jon; Chakravarty, Mallar M.] Univ Toronto, Inst Biomat & Biomed Engn, Toronto, ON M5T 1R8, Canada.
[Chakravarty, Mallar M.] Rotman Res Inst, Toronto, ON M6A 2E1, Canada.
RP Raznahan, A (reprint author), NIMH, Child Psychiat Branch, Bldg 10, Bethesda, MD 20892 USA.
EM raznahana@mail.nih.gov
RI Giedd, Jay/J-9644-2015
OI Giedd, Jay/0000-0003-2002-8978
NR 81
TC 60
Z9 61
U1 5
U2 18
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JAN 28
PY 2014
VL 111
IS 4
BP 1592
EP 1597
DI 10.1073/pnas.1316911111
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 297BV
UT WOS:000330231100082
PM 24474784
ER
PT J
AU Konkel, JE
Jin, WW
Abbatiello, B
Grainger, JR
Chen, WJ
AF Konkel, Joanne E.
Jin, Wenwen
Abbatiello, Brittany
Grainger, John R.
Chen, WanJun
TI Thymocyte apoptosis drives the intrathymic generation of regulatory T
cells
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE thymic Treg; phagocytes; TCR affinity
ID TRANSCRIPTION FACTOR FOXP3; GROWTH-FACTOR-BETA; THYMIC EPITHELIAL-CELLS;
TGF-BETA; NEGATIVE SELECTION; REG-CELLS; EXPRESSION; RECEPTOR; ANTIGEN;
DIFFERENTIATION
AB Maintenance of immune tolerance critically depends upon regulatory T cells that express the transcription factor forkhead box P3 (Foxp3). These CD4(+) T cells can be generated in the thymus, termed thymus-derived regulatory T cells (tTregs), but their developmental pathway remains incompletely understood. tTreg development has been shown to be delayed compared with that of CD4(+) single positive (SP) thymocytes, with tTregs being detected only in neonatal thymi by day 3 after birth. Here, we outline the reasons for this delayed emergence of Foxp3(+) tTregs and demonstrate that thymocyte apoptosis is intrinsically tied to tTreg development. We show that thymic apoptosis leads to the production of TGF beta intrathymically from thymic macrophages, dendritic cells, and epithelial cells. This TGF beta then induces foxp3 expression and drives tTreg generation. Thymocyte apoptosis has previously been shown to accelerate after birth, which drives increases in TGF beta in the neonatal thymus. We highlight a paucity of TGF beta in the neonatal thymus, accounting for the delayed development of tTregs compared with CD4(+) SP thymocytes. Importantly, we show that enhanced levels of apoptosis in the thymus result in an augmented tTreg population and, moreover, that decreasing thymic apoptosis results in reduced tTregs. In addition to this, we also show that T-cell receptor (TCR) signals of different affinity were all capable of driving tTreg development; however, to achieve this TGF beta signals must also be received concomitant with the TCR signal. Collectively, our results indicate that thymic apoptosis is a key event in tTreg generation and reveal a previously unrecognized apoptosis-TGF beta- Foxp3 axis that mediates the development of tTregs.
C1 [Konkel, Joanne E.; Jin, Wenwen; Abbatiello, Brittany; Chen, WanJun] Natl Inst Dent & Craniofacial Res, Mucosal Immunol Sect, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
[Grainger, John R.] NIAID, Program Barrier Immun & Repair, Mucosal Immunol Sect, Parasit Dis Lab,NIH, Bethesda, MD 20892 USA.
RP Chen, WJ (reprint author), Natl Inst Dent & Craniofacial Res, Mucosal Immunol Sect, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
EM wchen@dir.nidcr.nih.gov
OI Grainger, John/0000-0002-4052-5923
FU Intramural Research Programs of the NIDCR and of the National Institute
of Allergy and Infectious Diseases, National Institutes of Health
FX We thank Dr. N. Moutsopoulos and D. Zhang for technical expertise; Drs.
J. J. O'Shea and E. Wohlfert for critical reading of the manuscript; Dr.
K. Flanders for the LC( 1-30) antibody and staining protocols; the
National Heart, Lung, and Blood Institute and National Institute of
Dental and Craniofacial Research (NIDCR) FACS cores for cell sorting;
Dr. B. J. Fowlkes for FTOC advice; and Dr. K. Tarbell for use of
equipment. This work was supported by the Intramural Research Programs
of the NIDCR and of the National Institute of Allergy and Infectious
Diseases, National Institutes of Health.
NR 46
TC 16
Z9 18
U1 1
U2 7
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JAN 28
PY 2014
VL 111
IS 4
BP E465
EP E473
DI 10.1073/pnas.1320319111
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 297BV
UT WOS:000330231100009
PM 24474796
ER
PT J
AU Vega-Rodriguez, J
Ghosh, AK
Kanzok, SM
Dinglasan, RR
Wang, SB
Bongio, NJ
Kalume, DE
Miura, K
Long, CA
Pandey, A
Jacobs-Lorena, M
AF Vega-Rodriguez, Joel
Ghosh, Anil K.
Kanzok, Stefan M.
Dinglasan, Rhoel R.
Wang, Sibao
Bongio, Nicholas J.
Kalume, Dario E.
Miura, Kazutoyo
Long, Carole A.
Pandey, Akhilesh
Jacobs-Lorena, Marcelo
TI Multiple pathways for Plasmodium ookinete invasion of the mosquito
midgut
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID HUMAN MALARIA PARASITE; FIBRONECTIN-BINDING PROTEIN; ANOPHELES-GAMBIAE;
VECTOR MOSQUITOS; ALPHA-ENOLASE; HOST-CELLS; FALCIPARUM; TRANSMISSION;
SURFACE; BERGHEI
AB Plasmodium ookinete invasion of the mosquito midgut is a crucial step of the parasite life cycle but little is known about the molecular mechanisms involved. Previously, a phage display peptide library screen identified SM1, a peptide that binds to the mosquito midgut epithelium and inhibits ookinete invasion. SM1 was characterized as a mimotope of an ookinete surface enolase and SM1 presumably competes with enolase, the presumed ligand, for binding to a putative midgut receptor. Here we identify a mosquito midgut receptor that binds both SM1 and ookinete surface enolase, termed "enolase-binding protein" (EBP). Moreover, we determined that Plasmodium berghei parasites are heterogeneous for midgut invasion, as some parasite clones are strongly inhibited by SM1 whereas others are not. The SM1-sensitive parasites required the mosquito EBP receptor for midgut invasion whereas the SM1resistant parasites invaded the mosquito midgut independently of EBP. These experiments provide evidence that Plasmodium ookinetes can invade the mosquito midgut by alternate pathways. Furthermore, another peptide from the original phage display screen, midgut peptide 2 (MP2), strongly inhibited midgut invasion by P. berghei (SM1-sensitive and SM1-resistant) and Plasmodium falciparum ookinetes, suggesting that MP2 binds to a separate, universal receptor for midgut invasion.
C1 [Vega-Rodriguez, Joel; Ghosh, Anil K.; Dinglasan, Rhoel R.; Jacobs-Lorena, Marcelo] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Malaria Res Inst, W Harry Feinstone Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA.
[Kanzok, Stefan M.] Loyola Univ, Dept Biol, Chicago, IL 60660 USA.
[Wang, Sibao] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Plant Physiol & Ecol, Key Lab Insect Dev & Evolutionary Biol, Shanghai 200032, Peoples R China.
[Bongio, Nicholas J.] Duquesne Univ, Dept Biol Sci, Pittsburgh, PA 15282 USA.
[Kalume, Dario E.] Oswaldo Cruz Fdn FIOCRUZ, Inst Oswaldo Cruz, Lab Interdisciplinary Med Res, BR-21040900 Rio De Janeiro, RJ, Brazil.
[Miura, Kazutoyo; Long, Carole A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
[Pandey, Akhilesh] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA.
[Pandey, Akhilesh] Johns Hopkins Univ, Dept Biol Chem, Baltimore, MD 21205 USA.
[Pandey, Akhilesh] Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21205 USA.
[Pandey, Akhilesh] Johns Hopkins Univ, Dept Oncol, Baltimore, MD 21205 USA.
RP Jacobs-Lorena, M (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Malaria Res Inst, W Harry Feinstone Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA.
EM mlorena@jhsph.edu
OI Dinglasan, Rhoel/0000-0001-6563-1506; Dinglasan,
Rhoel/0000-0001-5433-8179
FU National Institutes of Health (NIH) [AI031478, RR00052]; Johns Hopkins
Malaria Research Institute; Bloomberg Family Foundation; intramural
program of NIAID/NIH; Program for Appropriate Technology in Health
(PATH) Malaria Vaccine Initiative
FX We thank the Johns Hopkins Malaria Research Institute mosquito and P.
falciparum core facilities for help with mosquito rearing and parasite
cultures. This work received financial support from the National
Institutes of Health (NIH) (Grant AI031478). Additional support was
provided by the Johns Hopkins Malaria Research Institute and the
Bloomberg Family Foundation. Supply of human blood was supported by NIH
Grant RR00052. The SMFA study at National Institute of Allergy and
Infectious Diseases (NIAID) was supported by the intramural program of
NIAID/NIH and by the Program for Appropriate Technology in Health (PATH)
Malaria Vaccine Initiative.
NR 42
TC 21
Z9 21
U1 2
U2 12
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JAN 28
PY 2014
VL 111
IS 4
BP E492
EP E500
DI 10.1073/pnas.1315517111
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 297BV
UT WOS:000330231100012
PM 24474798
ER
PT J
AU Wu, J
Tian, LJ
Yu, X
Pattaradilokrat, S
Li, J
Wang, MJ
Yu, WS
Qi, YW
Zeituni, AE
Nair, SC
Crampton, SP
Orandle, MS
Bolland, SM
Qi, CF
Long, CA
Myers, TG
Coligan, JE
Wang, RF
Su, XZ
AF Wu, Jian
Tian, Linjie
Yu, Xiao
Pattaradilokrat, Sittiporn
Li, Jian
Wang, Mingjun
Yu, Weishi
Qi, Yanwei
Zeituni, Amir E.
Nair, Sethu C.
Crampton, Steve P.
Orandle, Marlene S.
Bolland, Silvia M.
Qi, Chen-Feng
Long, Carole A.
Myers, Timothy G.
Coligan, John E.
Wang, Rongfu
Su, Xin-zhuan
TI Strain-specific innate immune signaling pathways determine malaria
parasitemia dynamics and host mortality
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE rodent; interferon; MDA5; MAVS; phagocytosis
ID EXPERIMENTAL CEREBRAL MALARIA; FALCIPARUM-PARASITIZED ERYTHROCYTES;
PATTERN-RECOGNITION RECEPTORS; PERSISTENT LCMV INFECTION; CYCLIC
GMP-AMP; PLASMODIUM-FALCIPARUM; CYTOSOLIC DNA; BLOOD-STAGE; DENDRITIC
CELLS; I INTERFERONS
AB Malaria infection triggers vigorous host immune responses; however, the parasite ligands, host receptors, and the signaling pathways responsible for these reactions remain unknown or controversial. Malaria parasites primarily reside within RBCs, thereby hiding themselves from direct contact and recognition by host immune cells. Host responses to malaria infection are very different from those elicited by bacterial and viral infections and the host receptors recognizing parasite ligands have been elusive. Here we investigated mouse genome-wide transcriptional responses to infections with two strains of Plasmodium yoelii (N67 and N67C) and discovered differences in innate response pathways corresponding to strain-specific disease phenotypes. Using in vitro RNAi-based gene knockdown and KO mice, we demonstrated that a strong type I IFN (IFN-I) response triggered by RNA polymerase III and melanoma differentiation-associated protein 5, not Toll-like receptors (TLRs), binding of parasite DNA/RNA contributed to a decline of parasitemia in N67-infected mice. We showed that conventional dendritic cells were the major sources of early IFN-I, and that surface expression of phosphatidylserine on infected RBCs might promote their phagocytic uptake, leading to the release of parasite ligands and the IFN-I response in N67 infection. In contrast, an elevated inflammatory response mediated by CD14/TLR and p38 signaling played a role in disease severity and early host death in N67C-infected mice. In addition to identifying cytosolic DNA/RNA sensors and signaling pathways previously unrecognized in malaria infection, our study demonstrates the importance of parasite genetic backgrounds in malaria pathology and provides important information for studying human malaria pathogenesis.
C1 [Wu, Jian; Pattaradilokrat, Sittiporn; Li, Jian; Qi, Yanwei; Zeituni, Amir E.; Nair, Sethu C.; Long, Carole A.; Su, Xin-zhuan] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
[Tian, Linjie; Crampton, Steve P.; Bolland, Silvia M.; Qi, Chen-Feng; Coligan, John E.] NIAID, Immunogenet Lab, NIH, Bethesda, MD 20892 USA.
[Yu, Xiao; Wang, Mingjun; Wang, Rongfu] Houston Methodist Res Inst, Ctr Inflammat & Epigenet, Houston, TX 77030 USA.
[Yu, Xiao] Sun Yat Sen Univ, Minist Educ, State Key Lab Biocontrol, Guangzhou 510006, Guangdong, Peoples R China.
[Yu, Xiao] Sun Yat Sen Univ, Minist Educ, Key Lab Gene Engn, Guangzhou 510006, Guangdong, Peoples R China.
[Pattaradilokrat, Sittiporn] Chulalongkorn Univ, Fac Sci, Dept Biol, Bangkok 10330, Thailand.
[Li, Jian; Qi, Yanwei] Xiamen Univ, Sch Life Sci, State Key Lab Cellular Stress Biol, Xiamen 361005, Fujian, Peoples R China.
[Yu, Weishi] NCI, Lab Canc Prevent, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Orandle, Marlene S.] NIAID, Comparat Med Branch, NIH, Bethesda, MD 20892 USA.
[Myers, Timothy G.] NIAID, Genom Technol Sect, Res Technol Branch, NIH, Bethesda, MD 20892 USA.
RP Su, XZ (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM rwang3@tmhs.org; xsu@niaid.nih.gov
RI Tian, Linjie/E-6878-2014; Wu, Jian/K-2038-2015;
OI Wu, Jian/0000-0001-8011-9551; Su, Xinzhuan/0000-0003-3246-3248
FU Intramural Research Program of the Division of Intramural Research at
the NIAID; National Institutes of Health (NIH); National Cancer
Institute; NIH [R01CA090327, R01CA101795]; China Scholarship Council
(CSC)
FX We thank Drs. Alan Sher and David Sacks for advice and National
Institute of Allergy and Infectious Diseases (NIAID) intramural editor
Brenda Rae Marshall for assistance. This work was supported by the
Intramural Research Program of the Division of Intramural Research at
the NIAID, National Institutes of Health (NIH) and in part by grants
from the National Cancer Institute, NIH R01CA090327 and R01CA101795 (to
R.W.). X.Y. is a recipient of The China Scholarship Council (CSC).
NR 56
TC 14
Z9 14
U1 1
U2 15
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 JAN 28
PY 2014
VL 111
IS 4
BP E511
EP E520
DI 10.1073/pnas.1316467111
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 297BV
UT WOS:000330231100014
PM 24474800
ER
PT J
AU Stamper, IJ
Jackson, E
Wang, XJ
AF Stamper, I. J.
Jackson, Elais
Wang, Xujing
TI Phase transitions in pancreatic islet cellular networks and implications
for type-1 diabetes
SO PHYSICAL REVIEW E
LA English
DT Article
ID PULSATILE INSULIN-SECRETION; TUMOR VASCULAR ARCHITECTURE; BETA-CELLS;
GAP-JUNCTION; HIGH GLUCOSE; INTERCELLULAR COMMUNICATION; CONNEXIN-43
EXPRESSION; ENDOTHELIAL-CELLS; HONEYMOON PHASE; DOWN-REGULATION
AB In many aspects the onset of a chronic disease resembles a phase transition in a complex dynamic system: Quantitative changes accumulate largely unnoticed until a critical threshold is reached, which causes abrupt qualitative changes of the system. In this study we examine a special case, the onset of type-1 diabetes (T1D), a disease that results from loss of the insulin-producing pancreatic islet beta cells. Within each islet, the beta cells are electrically coupled to each other via gap-junctional channels. This intercellular coupling enables the beta cells to synchronize their insulin release, thereby generating the multiscale temporal rhythms in blood insulin that are critical to maintaining blood glucose homeostasis. Using percolation theory we show how normal islet function is intrinsically linked to network connectivity. In particular, the critical amount of beta-cell death at which the islet cellular network loses site percolation is consistent with laboratory and clinical observations of the threshold loss of beta cells that causes islet functional failure. In addition, numerical simulations confirm that the islet cellular network needs to be percolated for beta cells to synchronize. Furthermore, the interplay between site percolation and bond strength predicts the existence of a transient phase of islet functional recovery after onset of T1D and introduction of treatment, potentially explaining the honeymoon phenomenon. Based on these results, we hypothesize that the onset of T1D may be the result of a phase transition of the islet beta-cell network.
C1 [Stamper, I. J.; Wang, Xujing] Univ Alabama Birmingham, Dept Phys, Birmingham, AL 35294 USA.
[Stamper, I. J.; Wang, Xujing] Univ Alabama Birmingham, Comprehens Diabet Ctr, Birmingham, AL USA.
[Jackson, Elais] Univ Alabama Birmingham, Dept Comp & Informat Sci, Birmingham, AL 35294 USA.
[Wang, Xujing] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA.
RP Wang, XJ (reprint author), Univ Alabama Birmingham, Dept Phys, Birmingham, AL 35294 USA.
EM Xujing.wang@nih.gov
FU Intramural NIH HHS [Z99 HL999999]; NIDDK NIH HHS [P30 DK056336]
NR 119
TC 5
Z9 5
U1 3
U2 6
PU AMER PHYSICAL SOC
PI COLLEGE PK
PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA
SN 2470-0045
EI 2470-0053
J9 PHYS REV E
JI Phys. Rev. E
PD JAN 27
PY 2014
VL 89
IS 1
AR 012719
DI 10.1103/PhysRevE.89.012719
PG 15
WC Physics, Fluids & Plasmas; Physics, Mathematical
SC Physics
GA AC0EO
UT WOS:000332167800003
PM 24580269
ER
PT J
AU Aimon, S
Callan-Jones, A
Berthaud, A
Pinot, M
Toombes, GES
Bassereau, P
AF Aimon, Sophie
Callan-Jones, Andrew
Berthaud, Alice
Pinot, Mathieu
Toombes, Gilman E. S.
Bassereau, Patricia
TI Membrane Shape Modulates Transmembrane Protein Distribution
SO DEVELOPMENTAL CELL
LA English
DT Article
ID LATERAL DIFFUSION; DENDRITIC SPINES; CURVATURE; LIPIDS; SEGREGATION;
CHANNEL; TUBES; AQPO
AB Although membrane shape varies greatly throughout the cell, the contribution of membrane curvature to transmembrane protein targeting is unknown because of the numerous sorting mechanisms that take place concurrently in cells. To isolate the effect of membrane shape, we used cell-sized giant unilamellar vesicles (GUVs) containing either the potassium channel KvAP or the water channel AQP0 to form membrane nanotubes with controlled radii. Whereas the AQP0 concentrations in flat and curved membranes were indistinguishable, KvAP was enriched in the tubes, with greater enrichment in more highly curved membranes. Fluorescence recovery after photobleaching measurements showed that both proteins could freely diffuse through the neck between the tube and GUV, and the effect of each protein on membrane shape and stiffness was characterized using a thermodynamic sorting model. This study establishes the importance of membrane shape for targeting transmembrane proteins and provides a method for determining the effective shape and flexibility of membrane proteins.
C1 [Aimon, Sophie; Berthaud, Alice; Pinot, Mathieu; Bassereau, Patricia] Inst Curie, Ctr Rech, F-75248 Paris, France.
[Aimon, Sophie; Berthaud, Alice; Bassereau, Patricia] CNRS, PhysicoChim Curie, UMR168, F-75248 Paris, France.
[Aimon, Sophie; Berthaud, Alice; Bassereau, Patricia] Univ Paris 06, F-75252 Paris, France.
[Aimon, Sophie] UCSD, Kavli Inst Brain & Mind, La Jolla, CA 92093 USA.
[Callan-Jones, Andrew] Univ Paris Diderot, CNRS, Lab Mat & Syst Complexes, UMR 7057, F-75205 Paris 13, France.
[Berthaud, Alice; Pinot, Mathieu; Bassereau, Patricia] Paris Sci & Lettres, CelTisPhyBio Labex, F-75005 Paris, France.
[Pinot, Mathieu] CNRS, UMR144, F-75248 Paris, France.
[Toombes, Gilman E. S.] NINDS, Mol Physiol & Biophys Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Toombes, GES (reprint author), NINDS, Mol Physiol & Biophys Sect, Porter Neurosci Res Ctr, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM gilman.toombes@nih.gov
RI Pinot, Mathieu/P-8192-2014;
OI Toombes, Gilman/0000-0001-8346-1790; Bassereau,
Patricia/0000-0002-8544-6778
FU Agence Nationale de la Recherche [BLAN-0057-01]; Federation "Dynamique
des systemes complexes hors equilibre" of the University Pierre et Marie
Curie; Institut Curie; Fondation pour la Recherche Medicale; CNRS action
"Prise de Risque"; Marie Curie fellowship; French research consortium
"CellTiss"
FX The authors thank J.B. Manneville for access to his FRAP setup, F.
Quemeneur and C. Prevost for help with the optical trap, F. Faqir, J.
Manzi, M. Garten, and S. Mangenot for help with biochemistry, T.
Bornschloegl for discussions, and B. Goud, L. Johannes, R. Martin, J.
Kalia, A. Manzo, and T. Katsuki for comments on the manuscript. The
authors acknowledge financial support from the Agence Nationale de la
Recherche (grant BLAN-0057-01), the Federation "Dynamique des systemes
complexes hors equilibre" of the University Pierre et Marie Curie, the
Institut Curie, and the "Fondation pour la Recherche Medicale" (to
S.A.), CNRS action "Prise de Risque" (to A.B.), a Marie Curie fellowship
(to G.E.S.T.), and the French research consortium "CellTiss" (to P.B.).
NR 37
TC 47
Z9 47
U1 7
U2 45
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 JAN 27
PY 2014
VL 28
IS 2
BP 212
EP 218
DI 10.1016/j.devcel.2013.12.012
PG 7
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 302EM
UT WOS:000330584600011
PM 24480645
ER
PT J
AU Bekhuis, T
Tseytlin, E
Mitchell, KJ
Demner-Fushman, D
AF Bekhuis, Tanja
Tseytlin, Eugene
Mitchell, Kevin J.
Demner-Fushman, Dina
TI Feature Engineering and a Proposed Decision-Support System for
Systematic Reviewers of Medical Evidence
SO PLOS ONE
LA English
DT Review
ID ALGORITHM; CLASSIFICATION; CLASSIFIERS; WORKLOAD; ROBUST
AB Objectives: Evidence-based medicine depends on the timely synthesis of research findings. An important source of synthesized evidence resides in systematic reviews. However, a bottleneck in review production involves dual screening of citations with titles and abstracts to find eligible studies. For this research, we tested the effect of various kinds of textual information (features) on performance of a machine learning classifier. Based on our findings, we propose an automated system to reduce screeing burden, as well as offer quality assurance.
Methods: We built a database of citations from 5 systematic reviews that varied with respect to domain, topic, and sponsor. Consensus judgments regarding eligibility were inferred from published reports. We extracted 5 feature sets from citations: alphabetic, alphanumeric(+), indexing, features mapped to concepts in systematic reviews, and topic models. To simulate a two-person team, we divided the data into random halves. We optimized the parameters of a Bayesian classifier, then trained and tested models on alternate data halves. Overall, we conducted 50 independent tests.
Results: All tests of summary performance (mean F3) surpassed the corresponding baseline, P<0.0001. The ranks for mean F3, precision, and classification error were statistically different across feature sets averaged over reviews; P-values for Friedman's test were.045,.002, and.002, respectively. Differences in ranks for mean recall were not statistically significant. Alphanumeric(+) features were associated with best performance; mean reduction in screening burden for this feature type ranged from 88% to 98% for the second pass through citations and from 38% to 48% overall.
Conclusions: A computer-assisted, decision support system based on our methods could substantially reduce the burden of screening citations for systematic review teams and solo reviewers. Additionally, such a system could deliver quality assurance both by confirming concordant decisions and by naming studies associated with discordant decisions for further consideration.
C1 [Bekhuis, Tanja; Tseytlin, Eugene; Mitchell, Kevin J.] Univ Pittsburgh, Sch Med, Dept Biomed Informat, Pittsburgh, PA 15260 USA.
[Demner-Fushman, Dina] US Natl Inst Hlth, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, Bethesda, MD USA.
RP Bekhuis, T (reprint author), Univ Pittsburgh, Sch Med, Dept Biomed Informat, Pittsburgh, PA 15260 USA.
EM tcb24@pitt.edu
RI Bekhuis, Tanja/D-4357-2015
OI Bekhuis, Tanja/0000-0002-8537-9077
FU US National Library of Medicine, National Institutes of Health
[4R00LM010943]
FX This research was suppported by the US National Library of Medicine,
National Institutes of Health, grant number 4R00LM010943. The funder had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 53
TC 2
Z9 2
U1 2
U2 10
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JAN 27
PY 2014
VL 9
IS 1
AR e86277
DI 10.1371/journal.pone.0086277
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 301BI
UT WOS:000330507300049
PM 24475099
ER
PT J
AU Brim, H
Abu-Asab, MS
Nouraie, M
Salazar, J
DeLeo, J
Razjouyan, H
Mokarram, P
Schaffer, AA
Naghibhossaini, F
Ashktorab, H
AF Brim, Hassan
Abu-Asab, Mones S.
Nouraie, Mehdi
Salazar, Jose
DeLeo, Jim
Razjouyan, Hadi
Mokarram, Pooneh
Schaffer, Alejandro A.
Naghibhossaini, Fakhraddin
Ashktorab, Hassan
TI An Integrative CGH, MSI and Candidate Genes Methylation Analysis of
Colorectal Tumors
SO PLOS ONE
LA English
DT Article
ID CANCER DCC GENE; MICROSATELLITE INSTABILITY; COLON-CANCER; CHROMOSOMAL
INSTABILITY; AFRICAN-AMERICANS; CLINICOPATHOLOGICAL FEATURES; GENOMIC
INSTABILITY; SUPPRESSOR GENES; PROSTATE-CANCER; GASTRIC-CANCER
AB Background: Different DNA aberrations processes can cause colorectal cancer (CRC). Herein, we conducted a comprehensive molecular characterization of 27 CRCs from Iranian patients.
Materials and Methods: Array CGH was performed. The MSI phenotype and the methylation status of 15 genes was established using MSP. The CGH data was compared to two established lists of 41 and 68 cancer genes, respectively, and to CGH data from African Americans. A maximum parsimony cladogram based on global aberrations was established.
Results: The number of aberrations seem to depend on the MSI status. MSI-H tumors displayed the lowest number of aberrations. MSP revealed that most markers were methylated, except RNF182 gene. P16 and MLH1 genes were primarily methylated in MSI-H tumors. Seven markers with moderate to high frequency of methylation (SYNE1, MMP2, CD109, EVL, RET, LGR and PTPRD) had very low levels of chromosomal aberrations. All chromosomes were targeted by aberrations with deletions more frequent than amplifications. The most amplified markers were CD248, ERCC6, ERGIC3, GNAS, MMP2, NF1, P2RX7, SFRS6, SLC29A1 and TBX22. Most deletions were noted for ADAM29, CHL1, CSMD3, FBXW7, GALNS, MMP2, NF1, PRKD1, SMAD4 and TP53. Aberrations targeting chromosome X were primarily amplifications in male patients and deletions in female patients. A finding similar to what we reported for African American CRC patients.
Conclusion: This first comprehensive analysis of CRC Iranian tumors reveals a high MSI rate. The MSI tumors displayed the lowest level of chromosomal aberrations but high frequency of methylation. The MSI-L were predominantly targeted with chromosomal instability in a way similar to the MSS tumors. The global chromosomal aberration profiles showed many similarities with other populations but also differences that might allow a better understanding of CRC's clinico-pathological specifics in this population.
C1 [Brim, Hassan; Nouraie, Mehdi; Ashktorab, Hassan] Howard Univ, Coll Med, Med & Canc Ctr, Dept Pathol, Washington, DC 20059 USA.
[Abu-Asab, Mones S.; Salazar, Jose] NEI, Histopathol Core, NIH, Bethesda, MD 20892 USA.
[DeLeo, Jim] NIH, Sect Biomed Comp, Ctr Clin, Bethesda, MD 20892 USA.
[Razjouyan, Hadi] Drexel Univ, Coll Med, Monmouth Med Ctr, Dept Med, Long Branch, NJ USA.
[Mokarram, Pooneh; Naghibhossaini, Fakhraddin] Shiraz Univ Med Sci, Dept Biochem, Shiraz, Iran.
[Schaffer, Alejandro A.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD USA.
RP Brim, H (reprint author), Howard Univ, Coll Med, Med & Canc Ctr, Dept Pathol, Washington, DC 20059 USA.
EM hbrim@howard.edu; hashktorab@howard.edu
FU National Cancer Institute (NCI), National Institutes of Health (NIH);
Intramural Research Program of the NIH, NCI; National Library of
Medicine; Research Centers in Minority Institutions (RCMI); [CA102681]
FX This work was supported by Grant #CA102681, funded by the National
Cancer Institute (NCI), National Institutes of Health (NIH), by the
Intramural Research Program of the NIH, NCI and National Library of
Medicine, and by Research Centers in Minority Institutions (RCMI). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 57
TC 11
Z9 14
U1 0
U2 10
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JAN 27
PY 2014
VL 9
IS 1
AR e82185
DI 10.1371/journal.pone.0082185
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 301BI
UT WOS:000330507300008
PM 24475022
ER
PT J
AU Cadet, JL
Brannock, C
Ladenheim, B
McCoy, MT
Krasnova, IN
Lehrmann, E
Becker, KG
Jayanthi, S
AF Cadet, Jean Lud
Brannock, Christie
Ladenheim, Bruce
McCoy, Michael T.
Krasnova, Irina N.
Lehrmann, Elin
Becker, Kevin G.
Jayanthi, Subramaniam
TI Enhanced Upregulation of CRH mRNA Expression in the Nucleus Accumbens of
Male Rats after a Second Injection of Methamphetamine Given Thirty Days
Later
SO PLOS ONE
LA English
DT Article
ID CORTICOTROPIN-RELEASING-FACTOR; CENTRAL-NERVOUS-SYSTEM; CONDITIONED
PLACE PREFERENCE; MESOLIMBIC DOPAMINERGIC SYSTEM; MEDIAL PREFRONTAL
CORTEX; PITUITARY-ADRENAL AXIS; STRESS-INDUCED RELAPSE; BEHAVIORAL
SENSITIZATION; RIBONUCLEIC-ACID; GENE-EXPRESSION
AB Methamphetamine (METH) is a widely abused amphetamine analog. Few studies have investigated the molecular effects of METH exposure in adult animals. Herein, we determined the consequences of an injection of METH (10 mg/kg) on transcriptional effects of a second METH (2.5 mg/kg) injection given one month later. We thus measured gene expression by microarray analyses in the nucleus accumbens (NAc) of 4 groups of rats euthanized 2 hours after the second injection: saline-pretreated followed by saline-challenged (SS) or METH-challenged (SM); and METH-pretreated followed by saline-challenged (MS) or METH-challenged (MM). Microarray analyses revealed that METH (2.5 mg/kg) produced acute changes (1.8-fold; P<0.01) in the expression of 412 (352 upregulated, 60 down-regulated) transcripts including cocaine and amphetamine regulated transcript, corticotropin-releasing hormone (Crh), oxytocin (Oxt), and vasopressin (Avp) that were upregulated. Injection of METH (10 mg/kg) altered the expression of 503 (338 upregulated, 165 down-regulated) transcripts measured one month later (MS group). These genes also included Cart and Crh. The MM group showed altered expression of 766 (565 upregulated, 201 down-regulated) transcripts including Avp, Cart, and Crh. The METH-induced increased Crh expression was enhanced in the MM group in comparison to SM and MS groups. Quantitative PCR confirmed the METH-induced changes in mRNA levels. Therefore, a single injection of METH produced long-lasting changes in gene expression in the rodent NAc. The long-term increases in Crh, Cart, and Avp mRNA expression suggest that METH exposure produced prolonged activation of the endogenous stress system. The METH-induced changes in oxytocin expression also suggest the possibility that this neuropeptide might play a significant role in the neuroplastic and affiliative effects of this drug.
C1 [Cadet, Jean Lud; Brannock, Christie; Ladenheim, Bruce; McCoy, Michael T.; Krasnova, Irina N.; Jayanthi, Subramaniam] NIDA, Mol Neuropsychiat Res Branch, Intramural Res Program, NIH, Baltimore, MD USA.
[Lehrmann, Elin; Becker, Kevin G.] NIA, Intramural Res Program, Gene Express & Genom Unit, NIH, Baltimore, MD 21224 USA.
RP Cadet, JL (reprint author), NIDA, Mol Neuropsychiat Res Branch, Intramural Res Program, NIH, Baltimore, MD USA.
EM jcadet@intra.nida.nih.gov
OI Lehrmann, Elin/0000-0002-9869-9475
FU Intramural Research Program of the DHHS/NIH/NIDA
FX This work was supported by funds of the Intramural Research Program of
the DHHS/NIH/NIDA. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 122
TC 10
Z9 10
U1 2
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 JAN 27
PY 2014
VL 9
IS 1
AR e84665
DI 10.1371/journal.pone.0084665
PG 22
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 301BI
UT WOS:000330507300013
PM 24475032
ER
PT J
AU Cukuroglu, E
Gursoy, A
Nussinov, R
Keskin, O
AF Cukuroglu, Engin
Gursoy, Attila
Nussinov, Ruth
Keskin, Ozlem
TI Non-Redundant Unique Interface Structures as Templates for Modeling
Protein Interactions
SO PLOS ONE
LA English
DT Article
ID HOT-SPOTS; DATA-BANK; HOMOLOGOUS PROTEINS; BINDING-ENERGY;
CLASSIFICATION; COMPLEXES; SEQUENCE; DATABASE; MOTIFS; SIMILARITIES
AB Improvements in experimental techniques increasingly provide structural data relating to protein-protein interactions. Classification of structural details of protein-protein interactions can provide valuable insights for modeling and abstracting design principles. Here, we aim to cluster protein-protein interactions by their interface structures, and to exploit these clusters to obtain and study shared and distinct protein binding sites. We find that there are 22604 unique interface structures in the PDB. These unique interfaces, which provide a rich resource of structural data of protein-protein interactions, can be used for template-based docking. We test the specificity of these non-redundant unique interface structures by finding protein pairs which have multiple binding sites. We suggest that residues with more than 40% relative accessible surface area should be considered as surface residues in template-based docking studies. This comprehensive study of protein interface structures can serve as a resource for the community. The dataset can be accessed at http://prism.ccbb.ku.edu.tr/piface.
C1 [Cukuroglu, Engin; Gursoy, Attila; Keskin, Ozlem] Koc Univ, Ctr Computat Biol & Bioinformat, Istanbul, Turkey.
[Cukuroglu, Engin; Gursoy, Attila; Keskin, Ozlem] Koc Univ, Coll Engn, Istanbul, Turkey.
[Nussinov, Ruth] NCI, Canc & Inflammat Program, Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, Frederick, MD 21701 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel.
RP Gursoy, A (reprint author), Koc Univ, Ctr Computat Biol & Bioinformat, Istanbul, Turkey.
EM agursoy@ku.edu.tr; okeskin@ku.edu.tr
RI Gursoy, Attila/E-9565-2015
OI Gursoy, Attila/0000-0002-2297-2113
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer
Research
FX This project has been funded in whole or in part with Federal funds from
the National Cancer Institute, National Institutes of Health, under
contract number HHSN261200800001E. The content of this publication does
not necessarily reflect the views or policies of the Department of
Health and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government.
This research was supported (in part) by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript. No additional
external funding received for this study.
NR 71
TC 19
Z9 19
U1 0
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JAN 27
PY 2014
VL 9
IS 1
AR e86738
DI 10.1371/journal.pone.0086738
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 301BI
UT WOS:000330507300105
PM 24475173
ER
PT J
AU Desai, A
Kevala, K
Kim, HY
AF Desai, Abhishek
Kevala, Karl
Kim, Hee-Yong
TI Depletion of Brain Docosahexaenoic Acid Impairs Recovery from Traumatic
Brain Injury
SO PLOS ONE
LA English
DT Article
ID POLYUNSATURATED FATTY-ACID; SPATIAL TASK-PERFORMANCE;
PARKINSONS-DISEASE; RATS; MICE; OMEGA-3-FATTY-ACIDS; MODEL;
NEUROPROTECTION; PROMOTES; DAMAGE
AB Omega-3 fatty acids are crucial for proper development and function of the brain where docosahexaenoic acid (DHA), the primary omega-3 fatty acid in the brain, is retained avidly by the neuronal membranes. We investigated the effect of DHA depletion in the brain on the outcome of traumatic brain injury (TBI). Pregnant mice were put on an omega-3 fatty acid adequate or deficient diet from gestation day 14 and the pups were raised on the respective diets. Continuation of this dietary regime for three generations resulted in approximately 70% loss of DHA in the brain. Controlled cortical impact was delivered to both groups of mice to produce severe TBI and the functional recovery was compared. Compared to the omega-3 adequate mice, the DHA depleted mice exhibited significantly slower recovery from motor deficits evaluated by the rotarod and the beam walk tests. Furthermore, the DHA deficient mice showed greater anxiety-like behavior tested in the open field test as well as cognitive deficits evaluated by the novel object recognition test. The level of alpha spectrin II breakdown products, the markers of TBI, was significantly elevated in the deficient mouse cortices, indicating that the injury is greater in the deficient brains. This observation was further supported by the reduction of NeuN positive cells around the site of injury in the deficient mice, indicating exacerbated neuronal death after injury. These results suggest an important influence of the brain DHA status on TBI outcome.
C1 [Desai, Abhishek; Kevala, Karl; Kim, Hee-Yong] NIAAA, Lab Mol Signaling, NIH, Bethesda, MD 20892 USA.
RP Kim, HY (reprint author), NIAAA, Lab Mol Signaling, NIH, Bethesda, MD 20892 USA.
EM hykim@nih.gov
FU Defense Medical Research and Development Program (DMRDP)
[W81XWH-11-2-0074]; National Institute of Alcohol Abuse and Alcoholism,
National Institutes of Health
FX This work was supported by the Defense Medical Research and Development
Program (DMRDP) (W81XWH-11-2-0074) and Intramural Research Program of
the National Institute of Alcohol Abuse and Alcoholism, 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 49
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U1 0
U2 9
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JAN 27
PY 2014
VL 9
IS 1
AR e86472
DI 10.1371/journal.pone.0086472
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 301BI
UT WOS:000330507300068
PM 24475126
ER
PT J
AU Yang, AX
Chong, NJ
Jiang, YF
Catalano, J
Puri, RK
Khleif, SN
AF Yang, Amy X.
Chong, Numju
Jiang, Yufei
Catalano, Jennifer
Puri, Raj K.
Khleif, Samir N.
TI Molecular Characterization of Antigen-Peptide Pulsed Dendritic Cells:
Immature Dendritic Cells Develop a Distinct Molecular Profile when
Pulsed with Antigen Peptide
SO PLOS ONE
LA English
DT Article
ID NECROSIS-FACTOR-ALPHA; OLIGONUCLEOTIDE MICROARRAYS; INTERFERON-GAMMA;
GENE-EXPRESSION; CERVICAL-CANCER; TUMOR-ANTIGEN; IN-VITRO; MATURATION;
INDUCTION; IMMUNITY
AB As dendritic cells (DCs) are the most potent professional antigen-presenting cells, they are being tested as cancer vaccines for immunotherapy of established cancers. Although numerous studies have characterized DCs by their phenotype and function, few have identified potential molecular markers of antigen presentation prior to vaccination of host. In this study we generated pre-immature DC (piDC), immature DC (iDC), and mature DC (mDC) from human peripheral blood monocytes (PBMC) obtained from HLA-A2 healthy donors, and pulsed them with human papillomavirus E7 peptide (p11-20), a class I HLA-A2 binding antigen. We then characterized DCs for cell surface phenotype and gene expression profile by microarray technology. We identified a set of 59 genes that distinguished three differentiation stages of DCs (piDC, iDC and mDC). When piDC, iDC and mDC were pulsed with E7 peptide for 2 hrs, the surface phenotype did not change, however, iDCs rather than mDCs showed transcriptional response by up-regulation of a set of genes. A total of 52 genes were modulated in iDC upon antigen pulsing. Elongation of pulse time for iDCs to 10 and 24 hrs did not significantly bring further changes in gene expression. The E7 peptide up-modulated immune response (KPNA7, IGSF6, NCR3, TREM2, TUBAL3, IL8, NFKBIA), pro-apoptosis (BTG1, SEMA6A, IGFBP3 and SRGN), anti-apoptosis (NFKBIA), DNA repair (MRPS11, RAD21, TXNRD1), and cell adhesion and cell migration genes (EPHA1, PGF, IL8 and CYR61) in iDCs. We confirmed our results by Q-PCR analysis. The E7 peptide but not control peptide (PADRE) induced up-regulation of NFKB1A gene only in HLA-A2 positive iDCs and not in HLA-A2 negative iDCs. These results suggest that E7 up-regulation of genes is specific and HLA restricted and that these genes may represent markers of antigen presentation and help rapidly assess the quality of dendritic cells prior to administration to the host.
C1 [Yang, Amy X.; Catalano, Jennifer; Puri, Raj K.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA.
[Chong, Numju; Jiang, Yufei; Khleif, Samir N.] NCI, Vaccine Branch, Bethesda, MD 20892 USA.
[Khleif, Samir N.] Georgia Regent Univ, Ctr Canc, Augusta, GA USA.
RP Puri, RK (reprint author), US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA.
EM raj.puri@fda.hhs.gov
NR 26
TC 2
Z9 2
U1 1
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JAN 27
PY 2014
VL 9
IS 1
AR e86306
DI 10.1371/journal.pone.0086306
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 301BI
UT WOS:000330507300052
PM 24475103
ER
PT J
AU Bae, WK
Hennighausen, L
AF Bae, Woo Kyun
Hennighausen, Lothar
TI Canonical and non-canonical roles of the histone methyltransferase EZH2
in mammary development and cancer
SO MOLECULAR AND CELLULAR ENDOCRINOLOGY
LA English
DT Article
DE EZH2; Histone methyltransferase; Breast
ID GROUP PROTEIN EZH2; B-CELL LYMPHOMAS; BREAST-CANCER; DNA METHYLATION;
EPITHELIAL-CELLS; PROSTATE-CANCER; GENE-EXPRESSION; LYSINE 27; POLYCOMB;
TARGET
AB Although hormones and downstream transcription factors are considered main drivers directing mammary gland development and oncogenic transformation, an emerging body of evidence suggests these processes are modulated by dynamic histone methylation landscapes. The methyltransferase EZH2 catalyzes the formation of trimethyl groups on lysine 27 of histone 3 (H3K27me3) and loss- and gain-of-function studies have provided insight into its role in normal mammary development and oncogenic transformation. EZH2 controls the homeostasis of mouse mammary stem cells, and mammary epithelium devoid of EZH2 does not undergo functional development during pregnancy, possibly due to a paucity of stem cells. EZH2 levels are frequently elevated in breast cancer suggesting a link between H3K27me3 and cell proliferation. In addition to its role as epigenetic regulator, recent studies have placed EZH2 into the category of transcriptional co-activators and thus opened the possibility of non-canonical signaling pathways. In contrast to solid tumors, loss of EZH2 from hematopoietic cells has been linked to malignancies (Fig. 1). The challenge will be to understand not only cell-specific functions of EZH2, but also the extent to which it relies on its enzymatic activity versus its ability to serve as a transcriptional co-factor. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
C1 [Bae, Woo Kyun; Hennighausen, Lothar] NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA.
[Bae, Woo Kyun] Chonnam Natl Univ, Dept Hematol & Oncol, Hwasun Hosp, Hwasun Gun, Jeollanamdo, South Korea.
[Hennighausen, Lothar] Dankook Univ, Natl Dept Nanobiomed Sci, Chungnam 330714, South Korea.
[Hennighausen, Lothar] Dankook Univ, WCU Res Ctr Nanobiomed Sci, Chungnam 330714, South Korea.
RP Bae, WK (reprint author), NIDDK, Lab Genet & Physiol, NIH, Bldg 8,Room 105, Bethesda, MD 20892 USA.
EM wookyun.bae@mail.nih.gov
FU intramural research program (IRP) of the NIDDK at the National
Institutes of Health (NIH), USA; World Class University Program,
Ministry of Education, Science and Technology, through the National
Research Foundation of Korea, South Korea [R31-100069]; WCU Research
Center, Dankook University; Research Institute of Medical Sciences,
Chonnam National University
FX This work was supported in part by the intramural research program (IRP)
of the NIDDK at the National Institutes of Health (NIH), USA, the World
Class University Program, Ministry of Education, Science and Technology,
through the National Research Foundation of Korea, South Korea
(R31-100069); WCU Research Center, Dankook University, and Research
Institute of Medical Sciences, Chonnam National University.
NR 38
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U1 2
U2 14
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0303-7207
J9 MOL CELL ENDOCRINOL
JI Mol. Cell. Endocrinol.
PD JAN 25
PY 2014
VL 382
IS 1
BP 593
EP 597
DI 10.1016/j.mce.2013.05.002
PG 5
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 299UQ
UT WOS:000330421600062
PM 23684884
ER
PT J
AU He, CY
Murabito, JM
AF He, Chunyan
Murabito, Joanne M.
TI Genome-wide association studies of age at menarche and age at natural
menopause
SO MOLECULAR AND CELLULAR ENDOCRINOLOGY
LA English
DT Review
DE Age at menarche; Age at natural menopause; Genome-wide association
studies; Linkage analysis; Candidate gene association studies
ID ESTROGEN-RECEPTOR-ALPHA; QUANTITATIVE TRAIT LOCI; BONE-MINERAL DENSITY;
METABOLIZING GENE POLYMORPHISMS; CAUSE-SPECIFIC MORTALITY;
CORONARY-ARTERY-DISEASE; ENDOMETRIAL CANCER-RISK; ALL-CAUSE MORTALITY;
37-YEAR FOLLOW-UP; BODY-MASS INDEX
AB Genome-wide association studies (GWAS) have been successful in uncovering genetic determinants of age at menarche and age at natural menopause. To date, more than 30 novel genetic loci have been identified in GWAS for age at menarche and 17 for age at natural menopause. These findings have stimulated a plethora of follow-up studies particularly with respect to the functional characterization of these novel loci and how these results can be translated into risk prediction. However, the genetic loci identified so far account for only a small fraction of the overall heritability. This review provides an overview of the current state of our knowledge of the genetic basis of menarche and menopause timing. It emphasizes recent GWAS results and outlines strategies for discovering the missing heritability and strategies to further our understanding of the underlying molecular mechanisms of the observed genetic associations. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
C1 [He, Chunyan] Indiana Univ Sch Med, Dept Publ Hlth, Indianapolis, IN 46202 USA.
[He, Chunyan] Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46202 USA.
[Murabito, Joanne M.] NHLBI, Framingham Heart Study, Framingham, MA 01701 USA.
[Murabito, Joanne M.] Boston Univ, Sch Med, Gen Internal Med Sect, Dept Med, Boston, MA 02118 USA.
RP He, CY (reprint author), Indiana Univ Sch Med, Dept Publ Hlth, 980 West Walnut St,R3-C241, Indianapolis, IN 46202 USA.
EM chunhe@iupui.edu; murabito@bu.edu
NR 153
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Z9 15
U1 6
U2 19
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0303-7207
J9 MOL CELL ENDOCRINOL
JI Mol. Cell. Endocrinol.
PD JAN 25
PY 2014
VL 382
IS 1
BP 767
EP 779
DI 10.1016/j.mce.2012.05.003
PG 13
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 299UQ
UT WOS:000330421600080
PM 22613007
ER
PT J
AU Redd, AD
AF Redd, Andrew D.
TI Research on hormonal contraception and HIV
SO LANCET
LA English
DT Letter
ID PREVENTION
C1 NIAID, NIH, Baltimore, MD 21205 USA.
RP Redd, AD (reprint author), NIAID, NIH, Baltimore, MD 21205 USA.
EM reddandrew@niaid.nih.gov
NR 6
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 0140-6736
EI 1474-547X
J9 LANCET
JI Lancet
PD JAN 25
PY 2014
VL 383
IS 9914
BP 305
EP 305
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 296VD
UT WOS:000330212600022
PM 24461118
ER
PT J
AU Derdeyn, CP
Chimowitz, MI
Lynn, MJ
Fiorella, D
Turan, TN
Janis, LS
Montgomery, J
Nizam, A
Lane, BF
Lutsep, HL
Barnwell, SL
Waters, MF
Hoh, BL
Hourihane, JM
Levy, EI
Alexandrov, AV
Harrigan, MR
Chiu, D
Klucznik, RP
Clark, JM
McDougall, CG
Johnson, MD
Pride, GL
Lynch, JR
Zaidat, OO
Rumboldt, Z
Cloft, HJ
AF Derdeyn, Colin P.
Chimowitz, Marc I.
Lynn, Michael J.
Fiorella, David
Turan, Tanya N.
Janis, L. Scott
Montgomery, Jean
Nizam, Azhar
Lane, Bethany F.
Lutsep, Helmi L.
Barnwell, Stanley L.
Waters, Michael F.
Hoh, Brian L.
Hourihane, J. Maurice
Levy, Elad I.
Alexandrov, Andrei V.
Harrigan, Mark R.
Chiu, David
Klucznik, Richard P.
Clark, Joni M.
McDougall, Cameron G.
Johnson, Mark D.
Pride, G. Lee, Jr.
Lynch, John R.
Zaidat, Osama O.
Rumboldt, Zoran
Cloft, Harry J.
CA Stenting Aggressive Med Management
TI Aggressive medical treatment with or without stenting in high-risk
patients with intracranial artery stenosis (SAMMPRIS): the final results
of a randomised trial
SO LANCET
LA English
DT Article
ID PREVENTING RECURRENT STROKE; ATHEROSCLEROTIC-DISEASE; ISCHEMIC-STROKE;
MANAGEMENT; ANGIOPLASTY; MECHANISMS; WINGSPAN; ASPIRIN; DESIGN; FUTURE
AB Background Early results of the Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis trial showed that, by 30 days, 33 (14.7%) of 224 patients in the stenting group and 13 (5.8%) of 227 patients in the medical group had died or had a stroke (percentages are product limit estimates), but provided insufficient data to establish whether stenting offered any longer-term benefit. Here we report the long-term outcome of patients in this trial.
Methods We randomly assigned (1:1, stratified by centre with randomly permuted block sizes) 451 patients with recent transient ischaemic attack or stroke related to 70-99% stenosis of a major intracranial artery to aggressive medical management (antiplatelet therapy, intensive management of vascular risk factors, and a lifestyle-modification programme) or aggressive medical management plus stenting with the Wingspan stent. The primary endpoint was any of the following:stroke or death within 30 days after enrolment, ischaemic stroke in the territory of the qualifying artery beyond 30 days of enrolment, or stroke or death within 30 days after a revascularisation procedure of the qualifying lesion during follow-up. Primary endpoint analysis of between-group differences with log-rank test was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT 00576693.
Findings During a median follow-up of 32.4 months, 34 (15%) of 227 patients in the medical group and 52 (23%) of 224 patients in the stenting group had a primary endpoint event. The cumulative probability of the primary endpoints was smaller in the medical group versus the percutaneous transluminal angioplasty and stenting (PTAS) group (p=0.0252). Beyond 30 days, 21 (10%) of 210 patients in the medical group and 19 (10%) of 191 patients in the stenting group had a primary endpoint. The absolute differences in the primary endpoint rates between the two groups were 7.1% at year 1 (95% CI 0.2 to 13.8%; p=0.0428), 6.5% at year 2 (-0.5 to 13.5%; p=0.07) and 9.0% at year 3 (1.5 to 16.5%; p=0.0193). The occurrence of the following adverse events was higher in the PTAS group than in the medical group:any stroke (59 [26%] of 224 patients vs 42 [19%] of 227 patients; p=0.0468) and major haemorrhage (29 [13%] of 224 patients vs 10 [4%] of 227 patients; p=0.0009).
Interpretation The early benefit of aggressive medical management over stenting with the Wingspan stent for high-risk patients with intracranial stenosis persists over extended follow-up. Our findings lend support to the use of aggressive medical management rather than PTAS with the Wingspan system in high-risk patients with atherosclerotic intracranial arterial stenosis.
C1 [Derdeyn, Colin P.] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA.
[Derdeyn, Colin P.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA.
[Derdeyn, Colin P.] Washington Univ, Sch Med, Dept Neurosurg, St Louis, MO 63110 USA.
[Chimowitz, Marc I.; Turan, Tanya N.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA.
[Lynn, Michael J.; Montgomery, Jean; Nizam, Azhar; Lane, Bethany F.] Emory Univ, Dept Biostat & Bioinformat, Rollins Sch Publ, Atlanta, GA 30322 USA.
[Fiorella, David] SUNY Stony Brook, Dept Neurosurg, Stony Brook, NY 11794 USA.
[Janis, L. Scott] NINDS, NIH, Bethesda, MD 20892 USA.
[Lutsep, Helmi L.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA.
[Barnwell, Stanley L.] Oregon Hlth & Sci Univ, Dept Neurol Surg, Portland, OR USA.
[Barnwell, Stanley L.] Oregon Hlth & Sci Univ, Dotter Intervent Inst, Portland, OR USA.
[Waters, Michael F.] Univ Florida, Dept Neurol, Gainesville, FL USA.
[Waters, Michael F.] Univ Florida, Dept Neurosci, Gainesville, FL 32610 USA.
[Hoh, Brian L.] Univ Florida, Dept Neurosurg, Gainesville, FL USA.
[Levy, Elad I.] SUNY Buffalo, Dept Neurosurg, Buffalo, NY 14260 USA.
[Hourihane, J. Maurice] Dent Neurol Inst, Buffalo, NY USA.
[Alexandrov, Andrei V.] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA.
[Harrigan, Mark R.] Univ Alabama Birmingham, Dept Neurosurg, Birmingham, AL USA.
[Chiu, David] Houston Methodist Hosp, Dept Neurol, Houston, TX USA.
[Klucznik, Richard P.] Houston Methodist Hosp, Dept Radiol, Houston, TX USA.
[Clark, Joni M.] Barrow Neurol Inst, Dept Neurol, Phoenix, AZ 85013 USA.
[McDougall, Cameron G.] Barrow Neurol Inst, Dept Neurosurg, Phoenix, AZ 85013 USA.
[Johnson, Mark D.] Univ Texas SW Med Ctr Dallas, Dept Neurol & Neurotherapeut, Dallas, TX 75390 USA.
[Pride, G. Lee, Jr.] Univ Texas SW Med Ctr Dallas, Dept Radiol, Dallas, TX 75390 USA.
[Pride, G. Lee, Jr.] Univ Texas SW Med Ctr Dallas, Dept Neurosurg, Dallas, TX 75390 USA.
[Lynch, John R.; Zaidat, Osama O.] Med Coll Wisconsin, Dept Neurol, Milwaukee, WI 53226 USA.
[Zaidat, Osama O.] Med Coll Wisconsin, Dept Radiol, Milwaukee, WI 53226 USA.
[Zaidat, Osama O.] Med Coll Wisconsin, Dept Neurosurg, Milwaukee, WI 53226 USA.
[Rumboldt, Zoran] Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA.
[Cloft, Harry J.] Mayo Clin, Dept Radiol, Rochester, MN USA.
RP Derdeyn, CP (reprint author), Washington Univ, Sch Med, Barnes Jewish Hosp, 510 South Kingshighway Blvd, St Louis, MO 63110 USA.
EM derdeync@wustl.edu
OI Alexandrov, Andrei V/0000-0001-8871-1023; Turan,
Tanya/0000-0001-5399-8845; Derdeyn, Colin/0000-0002-5932-2683
FU National Institute of Neurological Disorders and Stroke (NINDS); US
Public Health Service National Institute of Neurological Disorders and
Stroke (NINDS) [U01 NS058728]; National Institutes of Health; Medical
University of South Carolina [UL1RR029882]; University of Florida
[UL1RR029889]; University of Cincinnati [UL1RR029890]; University of
California, San Francisco [UL1RR024131]; Stryker Neurovascular;
AstraZeneca
FX This study was funded by a research grant (U01 NS058728) from the US
Public Health Service National Institute of Neurological Disorders and
Stroke (NINDS). Additionally, the following Clinical and Translational
Science Awards, funded by the National Institutes of Health, provided
local support for the assessment of patients in the trial: Medical
University of South Carolina (UL1RR029882), University of Florida
(UL1RR029889), University of Cincinnati (UL1RR029890), and University of
California, San Francisco (UL1RR024131). Stryker Neurovascular (formerly
Boston Scientific Neurovascular) provided study devices and supplemental
funding for third party device distribution, site monitoring, and study
auditing. This research was also supported by the Investigator-Sponsored
Study Program of AstraZeneca, which donated rosuvastatin (Crestor) to
study patients. INTERVENT provided the lifestyle modification programme
to the study at a discounted rate. The Regulatory and Clinical Research
Institute (RCRI; Minneapolis, MN, USA) provided assistance in designing
the site monitoring processes and did the site monitoring visits. The VA
Cooperative Studies Program Clinical Research Pharmacy Coordinating
Center (Albuquerque, NM, USA) handled the procurement, labelling,
distribution, and inventory management of the study devices and
rosuvastatin. Walgreens pharmacies provided study drugs other than
rosuvastatin to patients at a discounted price (paid for by the study).
The PACE self-assessment forms for physical activity and smoking
cessation were provided by the San Diego Center for Health
Interventions, LLC. We thank the patients for participating in this
study; Oscar Benavente, Carole White, Robert Hart, Pablo Pergola, and
Ana Roldan of the Secondary Prevention of Small Subcortical Strokes
trial (SPS3, NCT00059306) for assisting with the development and
implementation of the SAMMPRIS blood pressure management protocol;
George Howard and Thomas Brott for providing advice on study design and
other issues based on their experience with the Carotid
Revascularization Endarterectomy versus Stenting Trial (CREST,
NCT00004732); and Rie Calcaterra who helped with the SAMMPRIS grant
application and with the launching of the trial.
NR 30
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U1 1
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 JAN 25
PY 2014
VL 383
IS 9914
BP 333
EP 341
DI 10.1016/S0140-6736(13)62038-3
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 296VD
UT WOS:000330212600032
PM 24168957
ER
PT J
AU Elkins, P
Coleman, D
Burgess, J
Gardner, M
Hines, J
Scott, B
Kroenke, M
Larson, J
Lightner, M
Turner, G
White, J
Liu, P
AF Elkins, Phyllis
Coleman, Donna
Burgess, Jason
Gardner, Michael
Hines, John
Scott, Brendan
Kroenke, Michelle
Larson, Jami
Lightner, Melissa
Turner, Gregory
White, Jonathan
Liu, Paul
TI Characterization of the isomeric configuration and impurities of
(Z)-endoxifen by 2D NMR, high resolution LC-MS, and quantitative HPLC
analysis
SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
LA English
DT Article
DE Endoxifen; Isomeric characterization; LC-MS; NMR; Quantitative HPLC-UV
analysis
ID PERFORMANCE LIQUID-CHROMATOGRAPHY; TANDEM MASS-SPECTROMETRY;
BREAST-CANCER-CELLS; TAMOXIFEN; METABOLITES; QUANTIFICATION;
IDENTIFICATION; ENDOXIFEN; INHIBITOR; PLASMA
AB (Z)-Endoxifen (4-hydroxy-N-desmethyltamoxifen), an active metabolite generated via actions of CYP3A4/5 and CYP2D6, is a more potent selective estrogen receptor modulator (SERM) than tamoxifen. In the MCF-7 human mammary tumor xenograft model with female athymic mice, (Z)-endoxifen, at an oral dose of 48 mg/kg, significantly inhibits tumor growth. (Z)-Endoxifen's potential as an alternative therapeutic agent independent of CYP2D6 activities, which can vary widely in ER+ breast cancer patients, is being actively evaluated. This paper describes confirmation of the configuration of the active (Z)-isomer through 20 NMR experiments, including NOE (ROESY) to establish spatial proton-proton correlations, and identification of the major impurity as the (E)-isomer in endoxifen drug substance by HPLC/HRMS (HPLC/MS-TOF). Stability of NMR solutions was confirmed by HPLC/UV analysis. For pre-clinical studies, a reverse-phase HPLC-UV method, with methanol/water mobile phases containing 10 mM ammonium formate at pH 4.3, was developed and validated for the accurate quantitation and impurity profiling of drug substance and drug product. Validation included demonstration of linearity, method precision, accuracy, and specificity in the presence of impurities, excipients (for the drug product), and degradation products. Ruggedness and reproducibility of the method were confirmed by collaborative studies between two independent laboratories. The method is being applied for quality control of the API and oral drug product. Kinetic parameters of Z- to E-isomerization were also delineated in drug substance and in aqueous formulation, showing conversion at temperatures above 25 degrees C. (C) 2013 Elsevier B.V. All rights reserved.
C1 [Elkins, Phyllis; Coleman, Donna; Burgess, Jason; Gardner, Michael; Hines, John] RTI Int, Res Triangle Pk, NC 27709 USA.
[Scott, Brendan; Kroenke, Michelle; Larson, Jami; Lightner, Melissa; Turner, Gregory; White, Jonathan] MRIGlobal, Kansas City, MO 64110 USA.
[Liu, Paul] NCI, Pharmaceut Resources Branch, DCTD, NIH, Bethesda, MD 20892 USA.
RP Elkins, P (reprint author), RTI Int, 3040 Cornwallis Rd, Res Triangle Pk, NC 27709 USA.
EM elkins@rti.org; jwhite@mriglobal.org; liup@dtpepn.nci.nih.gov
FU Pharmaceutical Research Branch, DTP, DCTD, NCI, NIH, DHHS [N02-CM-72201,
N02-CM-72202]
FX This work was funded by the Pharmaceutical Research Branch, DTP, DCTD,
NCI, NIH, DHHS under Contract Nos. N02-CM-72201 and -72202.
NR 18
TC 10
Z9 10
U1 4
U2 27
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0731-7085
EI 1873-264X
J9 J PHARMACEUT BIOMED
JI J. Pharm. Biomed. Anal.
PD JAN 25
PY 2014
VL 88
BP 174
EP 179
DI 10.1016/j.jpba.2013.07.010
PG 6
WC Chemistry, Analytical; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA 287HN
UT WOS:000329532800025
PM 24055701
ER
PT J
AU Kim, KI
Simon, R
AF Kim, Kyung In
Simon, Richard
TI Using single cell sequencing data to model the evolutionary history of a
tumor
SO BMC BIOINFORMATICS
LA English
DT Article
ID CANCER; AMPLIFICATION; MUTATIONS; LINEAGE; TREES; DNA
AB Background: The introduction of next-generation sequencing (NGS) technology has made it possible to detect genomic alterations within tumor cells on a large scale. However, most applications of NGS show the genetic content of mixtures of cells. Recently developed single cell sequencing technology can identify variation within a single cell. Characterization of multiple samples from a tumor using single cell sequencing can potentially provide information on the evolutionary history of that tumor. This may facilitate understanding how key mutations accumulate and evolve in lineages to form a heterogeneous tumor.
Results: We provide a computational method to infer an evolutionary mutation tree based on single cell sequencing data. Our approach differs from traditional phylogenetic tree approaches in that our mutation tree directly describes temporal order relationships among mutation sites. Our method also accommodates sequencing errors. Furthermore, we provide a method for estimating the proportion of time from the earliest mutation event of the sample to the most recent common ancestor of the sample of cells. Finally, we discuss current limitations on modeling with single cell sequencing data and possible improvements under those limitations.
Conclusions: Inferring the temporal ordering of mutational sites using current single cell sequencing data is a challenge. Our proposed method may help elucidate relationships among key mutations and their role in tumor progression.
C1 [Kim, Kyung In; Simon, Richard] NCI, Biometr Res Branch, Bethesda, MD 20892 USA.
RP Simon, R (reprint author), NCI, Biometr Res Branch, 9609 Med Ctr Dr,MSC 9735, Bethesda, MD 20892 USA.
EM rsimon@mail.nih.gov
NR 27
TC 11
Z9 12
U1 0
U2 13
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD JAN 24
PY 2014
VL 15
AR 27
DI 10.1186/1471-2105-15-27
PG 13
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA AF1GS
UT WOS:000334463000002
PM 24460695
ER
PT J
AU Park, M
Ohana, E
Choi, SY
Lee, MS
Park, JH
Muallem, S
AF Park, Meeyoung
Ohana, Ehud
Choi, Soo Young
Lee, Myeong-Sok
Park, Jong Hoon
Muallem, Shmuel
TI Multiple Roles of the SO42-/Cl-/OH- Exchanger Protein Slc26a2 in
Chondrocyte Functions
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Anion Transport; Cellular Regulation; Chondrocytes; Insulin-like Growth
Factor (IGF); Transporters
ID DYSPLASIA SULFATE TRANSPORTER; GROWTH-FACTOR-I; BONE-GROWTH;
PROTEOGLYCAN SULFATION; SIGNALING PATHWAYS; CARTILAGE; FAMILY;
DIFFERENTIATION; PLATE; MUTATIONS
AB Mutations in the SO42-/Cl-/OH- exchanger Slc26a2 cause the disease diastrophic dysplasia (DTD), resulting in aberrant bone development and, therefore, skeletal deformities. DTD is commonly attributed to a lack of chondrocyte SO42- uptake and proteoglycan sulfation. However, the skeletal phenotype of patients with DTD is typified by reduction in cartilage and osteoporosis of the long bones. Chondrocytes of patients with DTD are irregular in size and have a reduced capacity for proliferation and terminal differentiation. This raises the possibility of additional roles for Slc26a2 in chondrocyte function. Here, we examined the roles of Slc26a2 in chondrocyte biology using two distinct systems: mouse progenitor mesenchymal cells differentiated to chondrocytes and freshly isolated mouse articular chondrocytes differentiated into hypertrophic chondrocytes. Slc26a2 expression was manipulated acutely by delivery of Slc26a2 or shSlc26a2 with lentiviral vectors. We demonstrate that slc26a2 is essential for chondrocyte proliferation and differentiation and for proteoglycan synthesis. Slc26a2 also regulates the terminal stage of chondrocyte cell size expansion. These findings reveal multiple roles for Slc26a2 in chondrocyte biology and emphasize the importance of Slc26a2-mediated protein sulfation in cell signaling, which may account for the complex phenotype of DTD.
C1 [Park, Meeyoung; Lee, Myeong-Sok; Park, Jong Hoon] Sookmyung Womens Univ, Res Ctr Womens Dis, Dept Biol Sci, Seoul 140742, South Korea.
[Ohana, Ehud; Muallem, Shmuel] Natl Inst Dent & Craniofacial Res, Epithelial Signaling & Transport Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA.
[Choi, Soo Young] Hallym Univ, Inst Biosci & Biotechnol, Dept Biomed Sci & Res, Chunchon 200702, South Korea.
RP Park, JH (reprint author), Sookmyung Womens Univ, Res Ctr Womens Dis, Dept Biol Sci, Seoul 140742, South Korea.
EM parkjh@sookmyung.ac.kr; shmuel.muallem@nih.gov
FU National Institutes of Health [ZIA DE000735]; National Research
Foundation [NRF-2008-359-C00029, NRF-2009-0071060]; MSIP
[2013R1A2A1A01011908]; Korean government
FX This work was supported, in whole or in part, by National Institutes of
Health Intramural Grant ZIA DE000735. This work was also supported by
National Research Foundation Grants NRF-2008-359-C00029 and
NRF-2009-0071060] and MSIP Grant 2013R1A2A1A01011908 funded by the
Korean government.
NR 41
TC 3
Z9 3
U1 1
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JAN 24
PY 2014
VL 289
IS 4
BP 1993
EP 2001
DI 10.1074/jbc.M113.503466
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AA5IV
UT WOS:000331130200011
PM 24302720
ER
PT J
AU Shrestha, SS
Pine, DS
Luckenbaugh, DA
Varnas, K
Henter, ID
Innis, RB
Mathe, AA
Svenningsson, P
AF Shrestha, Stal Saurav
Pine, Daniel S.
Luckenbaugh, David A.
Varnas, Katarina
Henter, Ioline D.
Innis, Robert B.
Mathe, Aleksander A.
Svenningsson, Per
TI Antidepressant effects on serotonin 1A/1B receptors in the rat brain
using a gene x environment model
SO NEUROSCIENCE LETTERS
LA English
DT Article
DE FSL/FRL (Flinders sensitive/resistant line); Serotonin 1A/1B (5-HT1A/1B)
receptors; Escitalopram; Nortriptyline; PFC (prefrontal cortex);
Hippocampus; Gene-environment (GxE)
ID FLINDERS SENSITIVE LINE; HIPPOCAMPAL CYTOGENESIS; MATERNAL SEPARATION;
DEPRESSION MODEL; TRANSPORTER GENE; 5-HT1B RECEPTOR; ANIMAL-MODEL;
PSYCHIATRY; DENSITY; MICE
AB A gene-environment (GxE) interaction is implicated in both the pathophysiology and treatment of major depressive disorder (MDD). This study modeled the effects of genetic vulnerability by using the Flinders sensitive line (FSL), a rat model of depression and its control counterpart the Flinders resistant line (FRL). The effects of environmental vulnerability (e.g., early-life stress) were modeled by using maternal separation. Rats (n = 105) were drawn from four groups reflecting experimental crossing of strain (FSL vs. FRL) and early-life stress (high vs. low) to assess the effects of two antidepressants (escitalopram or nortriptyline) compared to vehicle. Quantitative in vitro autoradiography was performed using [I-125]MPPI (5-HT1A) and [I-125]CYP (5-HT1B) in prefrontal cortex (PFC) and hippocampus. Stringent, Bonferroni-corrected statistical analyses showed significant strain-by-rearing-by-treatment (three-way) interactions in PFC 5-HT1A and hippocampal 5-HT1B receptors. Either vulnerability reduced serotonergic binding; no additive effects were associated with the two vulnerabilities. Both antidepressants increased hippocampal 5-HT1B receptor binding; however, only nortriptyline selectively increased PFC 5-HTIA receptor binding. Taken together, our findings demonstrate that antidepressant effects on the serotonergic system are shaped by a GxE interaction that depends on antidepressant class and brain region. (c) 2013 Elsevier Ireland Ltd. All rights reserved.
C1 [Shrestha, Stal Saurav; Varnas, Katarina; Mathe, Aleksander A.; Svenningsson, Per] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
[Shrestha, Stal Saurav; Pine, Daniel S.; Luckenbaugh, David A.; Henter, Ioline D.; Innis, Robert B.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA.
RP Shrestha, SS (reprint author), 10 Ctr Dr B1D43 MSC 1026, Bethesda, MD 20892 USA.
EM shresthas@mail.nih.gov
FU Swedish Medical Research Council; Intramural Research Program of the
National Institute of Mental Health (IRP-NIMH); Karolinska Institutet
(KI)
FX The authors acknowledge the support of the Swedish Medical Research
Council, the Intramural Research Program of the National Institute of
Mental Health (IRP-NIMH), and the Karolinska Institutet (KI). The
authors thank Martin Werme, Aram El Khoury, Paul Cumming, Mirko Diksic,
Jeih-San Liow, Robert Harris, and the joint NIH-KI Doctoral Program in
Neuroscience.
NR 31
TC 4
Z9 4
U1 2
U2 5
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 JAN 24
PY 2014
VL 559
BP 163
EP 168
DI 10.1016/j.neulet.2013.11.034
PG 6
WC Neurosciences
SC Neurosciences & Neurology
GA AA3VD
UT WOS:000331021900031
PM 24287374
ER
PT J
AU Dunty, WC
Kennedy, MWL
Chalamalasetty, RB
Campbell, K
Yamaguchi, TP
AF Dunty, William C., Jr.
Kennedy, Mark W. L.
Chalamalasetty, Ravindra B.
Campbell, Kenneth
Yamaguchi, Terry P.
TI Transcriptional Profiling of Wnt3a Mutants Identifies Sp Transcription
Factors as Essential Effectors of the Wnt/beta-catenin Pathway in
Neuromesodermal Stem Cells
SO PLOS ONE
LA English
DT Article
ID BETA-CATENIN; PARAXIAL MESODERM; NEGATIVE REGULATOR; AXIAL PROGENITORS;
MOUSE; GENE; SEGMENTATION; BRACHYURY; TARGET; SPECIFICATION
AB Neuromesodermal (NM) stem cells reside in the primitive streak (PS) of gastrulating vertebrate embryos and generate precursors of the spinal cord and musculoskeletal system. Although Wnt3a/beta-catenin signaling is crucial for NM stem cell maintenance and differentiation, few key transcriptional effectors have been identified. Through a concerted transcriptional profiling and genetic approach we have determined that two Zn2+-finger transcription factors, Sp5 and Sp8, are regulated by Wnt3a in the PS, and are essential for neural and musculoskeletal patterning. These results identify Sp5 and Sp8 as pivotal downstream effectors of Wnt3a, and suggest that they are essential for the self-renewal and differentiation of NM stem cells.
C1 [Dunty, William C., Jr.; Kennedy, Mark W. L.; Chalamalasetty, Ravindra B.; Yamaguchi, Terry P.] NCI, Canc & Dev Biol Lab, Ctr Canc Res, NIH, Frederick, MD 21701 USA.
[Campbell, Kenneth] Cincinnati Childrens Hosp Med Ctr, Div Dev Biol, Cincinnati, OH 45229 USA.
RP Yamaguchi, TP (reprint author), NCI, Canc & Dev Biol Lab, Ctr Canc Res, NIH, Frederick, MD 21701 USA.
EM yamagute@mail.nih.gov
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 39
TC 17
Z9 18
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 JAN 24
PY 2014
VL 9
IS 1
AR e87018
DI 10.1371/journal.pone.0087018
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 298QQ
UT WOS:000330339800078
PM 24475213
ER
PT J
AU Parker, HG
Ostrander, EA
AF Parker, Heidi G.
Ostrander, Elaine A.
TI Hiding in Plain View-An Ancient Dog in the Modern World
SO SCIENCE
LA English
DT Editorial Material
ID DEVIL SARCOPHILUS-HARRISII; TRANSMISSIBLE CANCER; TASMANIAN DEVIL;
EVOLUTION
C1 [Parker, Heidi G.; Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Parker, HG (reprint author), NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
EM eostrand@mail.nih.gov
OI Ostrander, Elaine/0000-0001-6075-9738
FU Intramural NIH HHS [Z99 HG999999]
NR 10
TC 3
Z9 3
U1 0
U2 26
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 JAN 24
PY 2014
VL 343
IS 6169
BP 376
EP 378
DI 10.1126/science.1248812
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 294IR
UT WOS:000330039300033
PM 24458629
ER
PT J
AU Spencer, SP
Wilhelm, C
Yang, Q
Hall, JA
Bouladoux, N
Boyd, A
Nutman, TB
Urban, JF
Wang, J
Ramalingam, TR
Bhandoola, A
Wynn, TA
Belkaid, Y
AF Spencer, S. P.
Wilhelm, C.
Yang, Q.
Hall, J. A.
Bouladoux, N.
Boyd, A.
Nutman, T. B.
Urban, J. F., Jr.
Wang, J.
Ramalingam, T. R.
Bhandoola, A.
Wynn, T. A.
Belkaid, Y.
TI Adaptation of Innate Lymphoid Cells to a Micronutrient Deficiency
Promotes Type 2 Barrier Immunity
SO SCIENCE
LA English
DT Article
ID VITAMIN-A-DEFICIENCY; RETINOIC ACID; HELMINTH INFECTION; T-CELLS;
RESPONSES; INFLAMMATION; INTESTINE; CHILDREN; ALPHA; IL-13
AB How the immune system adapts to malnutrition to sustain immunity at barrier surfaces, such as the intestine, remains unclear. Vitamin A deficiency is one of the most common micronutrient deficiencies and is associated with profound defects in adaptive immunity. Here, we found that type 3 innate lymphoid cells (ILC3s) are severely diminished in vitamin A-deficient settings, which results in compromised immunity to acute bacterial infection. However, vitamin A deprivation paradoxically resulted in dramatic expansion of interleukin-13 (IL-13)-producing ILC2s and resistance to nematode infection in mice, which revealed that ILCs are primary sensors of dietary stress. Further, these data indicate that, during malnutrition, a switch to innate type 2 immunity may represent a powerful adaptation of the immune system to promote host survival in the face of ongoing barrier challenges.
C1 [Spencer, S. P.; Wilhelm, C.; Hall, J. A.; Bouladoux, N.; Ramalingam, T. R.; Wynn, T. A.; Belkaid, Y.] NIAID, Immun Barrier Sites Initiat, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Spencer, S. P.; Wilhelm, C.; Hall, J. A.; Bouladoux, N.; Belkaid, Y.] NIAID, Mucosal Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Spencer, S. P.; Yang, Q.; Bhandoola, A.] Univ Penn, Dept Pathol & Lab Med, Inst Immunol, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Boyd, A.; Nutman, T. B.] NIAID, Helminth Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Urban, J. F., Jr.] USDA, Beltsville Human Nutr Res Ctr, Diet Genom & Immunol Lab, Beltsville, MD 20705 USA.
[Wang, J.] Univ Calif Berkeley, Program Metab Biol Nutr Sci & Toxicol, Berkeley, CA 94720 USA.
[Ramalingam, T. R.; Wynn, T. A.] NIAID, Immunopathogenesis Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Belkaid, Y (reprint author), NIAID, Immun Barrier Sites Initiat, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM ybelkaid@niaid.nih.gov
OI Urban, Joseph/0000-0002-1590-8869
FU Division of Intramural Research of the National Institute of Allergy and
Infectious Diseases (NIAID), NIH; Office of Dietary Supplements, NIH;
NIH [F30 DK094708]; Human Frontier Science Program; U.S. Department of
Agriculture-Agricultural Research Service [1254-32000-094-00D]; Damon
Runyon Cancer Research Foundation
FX This work was supported by the Division of Intramural Research of the
National Institute of Allergy and Infectious Diseases (NIAID), NIH;
Office of Dietary Supplements, NIH; NIH grant F30 DK094708 (S.P.S.);
Human Frontier Science Program (C.W.); U.S. Department of
Agriculture-Agricultural Research Service project plan
#1254-32000-094-00D (J.U.); and by the Damon Runyon Cancer Research
Foundation (Dale F. and Betty Ann Frey Fellow, J.A.H.). We thank the
NIAID animal facility staff; K. Holmes and the NIAID sorting facility,
in particular, C. Eigsti and E. Stregevsky; and K. Beacht and the NIAID
gnotobiotic facility, in particular, C. Avecedo and D. Trageser-Cesler
for technical assistance. We thank D. Artis for providing C. rodentium,
W. J. Leonard for providing TSLPR-/- mice, and W. Paul for
providing IL33R-/- mice. We thank the Belkaid lab for
critical discussions regarding the manuscript. The data presented in
this manuscript are tabulated in the main paper and the supplementary
materials.
NR 33
TC 121
Z9 128
U1 4
U2 24
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 JAN 24
PY 2014
VL 343
IS 6169
BP 432
EP 437
DI 10.1126/science.1247606
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 294IR
UT WOS:000330039300053
PM 24458645
ER
PT J
AU Mollapour, M
Bourboulia, D
Beebe, K
Woodford, MR
Polier, S
Hoang, A
Chelluri, R
Li, Y
Guo, A
Lee, MJ
Fotooh-Abadi, E
Khan, S
Prince, T
Miyajima, N
Yoshida, S
Tsutsumi, S
Xu, WP
Panaretou, B
Stetler-Stevenson, WG
Bratslavsky, G
Trepel, JB
Prodromou, C
Neckers, L
AF Mollapour, Mehdi
Bourboulia, Dimitra
Beebe, Kristin
Woodford, Mark R.
Polier, Sigrun
Hoang, Anthony
Chelluri, Raju
Li, Yu
Guo, Allan
Lee, Min-Jung
Fotooh-Abadi, Elham
Khan, Sahar
Prince, Thomas
Miyajima, Naoto
Yoshida, Soichiro
Tsutsumi, Shinji
Xu, Wanping
Panaretou, Barry
Stetler-Stevenson, William G.
Bratslavsky, Gennady
Trepel, Jane B.
Prodromou, Chrisostomos
Neckers, Len
TI Asymmetric Hsp90 N Domain SUMOylation Recruits Aha1 and ATP-Competitive
Inhibitors
SO MOLECULAR CELL
LA English
DT Article
ID SHOCK TRANSCRIPTION FACTOR; MOLECULAR CHAPERONE HSP90; CO-CHAPERONES;
IN-VIVO; COCHAPERONE AHA1; POSTTRANSLATIONAL MODIFICATIONS; TYROSINE
PHOSPHORYLATION; CRYSTAL-STRUCTURE; DRUG-SENSITIVITY; STEROID-RECEPTOR
AB The stability and activity of numerous signaling proteins in both normal and cancer cells depends on the dimeric molecular chaperone heat shock protein 90 (Hsp90). Hsp90's function is coupled to ATP binding and hydrolysis and requires a series of conformational changes that are regulated by cochaperones and numerous posttranslational modifications (PTMs). SUMOylation is one of the least-understood Hsp90 PTMs. Here, we show that asymmetric SUMOylation of a conserved lysine residue in the N domain of both yeast (K178) and human (K191) Hsp90 facilitates both recruitment of the adenosine triphosphatase (ATPase)-activating cochaperone Aha1 and, unexpectedly, the binding of Hsp90 inhibitors, suggesting that these drugs associate preferentially with Hsp90 proteins that are actively engaged in the chaperone cycle. Importantly, cellular transformation is accompanied by elevated steady-state N domain SUMOylation, and increased Hsp90 SUMOylation sensitizes yeast and mammalian cells to Hsp90 inhibitors, providing a mechanism to explain the sensitivity of cancer cells to these drugs.
C1 [Mollapour, Mehdi; Bourboulia, Dimitra; Woodford, Mark R.; Chelluri, Raju; Bratslavsky, Gennady] SUNY Upstate Med Univ, Dept Urol, Syracuse, NY 13210 USA.
[Mollapour, Mehdi; Bourboulia, Dimitra] SUNY Upstate Med Univ, Dept Biochem & Mol Biol, Syracuse, NY 13210 USA.
[Mollapour, Mehdi; Bourboulia, Dimitra; Bratslavsky, Gennady] SUNY Upstate Med Univ, Canc Res Inst, Syracuse, NY 13210 USA.
[Mollapour, Mehdi; Beebe, Kristin; Hoang, Anthony; Khan, Sahar; Prince, Thomas; Miyajima, Naoto; Yoshida, Soichiro; Tsutsumi, Shinji; Xu, Wanping; Neckers, Len] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Bourboulia, Dimitra; Stetler-Stevenson, William G.] NCI, Radiat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Lee, Min-Jung; Fotooh-Abadi, Elham; Trepel, Jane B.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Polier, Sigrun; Prodromou, Chrisostomos] Univ Sussex, Genome Damage & Stabil Ctr, Brighton BN1 9RQ, E Sussex, England.
[Li, Yu; Guo, Allan] Cell Signaling Technol, Danvers, MA 01923 USA.
[Panaretou, Barry] Kings Coll London, Inst Pharmaceut Sci, London SE1 9NH, England.
RP Mollapour, M (reprint author), SUNY Upstate Med Univ, Dept Urol, 750 East Adams St, Syracuse, NY 13210 USA.
EM mollapom@upstate.edu; neckers@nih.gov
RI Stetler-Stevenson, William/H-6956-2012;
OI Stetler-Stevenson, William/0000-0002-5500-5808; Prodromou,
Chrisostomos/0000-0003-4320-1147
FU National Cancer Institute; SUNY Upstate Medical University
FX We thank Dr. J. Johnson (University of Idaho) for STE11 Delta N plasmid,
Dr. J.L. Brodsky (University of Pittsburgh) for CFTR-HA plasmid, Dr. T.
Haystead (Duke University) for the Hsp90 inhibitor SNX-2112, Dr. W. Ying
(Synta Pharmaceuticals) for the Hsp90 inhibitor ganetespib, and Dr K.
Robzyk (Memorial Sloan-Kettering Cancer Center) for SUMO-1, SUMO-2, and
SUMO-3 HA-tagged plasmids. We are also grateful to Dr. A. Zuehlke (NCI)
for helpful discussion. This work was supported with funds from the
Intramural Research Program of the National Cancer Institute (L.N.) and
the SUNY Upstate Medical University (M.M.).
NR 58
TC 38
Z9 38
U1 2
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
EI 1097-4164
J9 MOL CELL
JI Mol. Cell
PD JAN 23
PY 2014
VL 53
IS 2
BP 317
EP 329
DI 10.1016/j.molcel.2013.12.007
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 300XD
UT WOS:000330496400013
PM 24462205
ER
PT J
AU Calhoun, KC
Padilla-Banks, E
Jefferson, WN
Liu, LW
Gerrish, KE
Young, SL
Wood, CE
Hunt, PA
VandeVoort, CA
Williams, CJ
AF Calhoun, Kathryn C.
Padilla-Banks, Elizabeth
Jefferson, Wendy N.
Liu, Liwen
Gerrish, Kevin E.
Young, Steven L.
Wood, Charles E.
Hunt, Patricia A.
VandeVoort, Catherine A.
Williams, Carmen J.
TI Bisphenol A Exposure Alters Developmental Gene Expression in the Fetal
Rhesus Macaque Uterus
SO PLOS ONE
LA English
DT Article
ID FOOT-GENITAL SYNDROME; WIDESPREAD EXPOSURE; MACACA-FASCICULARIS;
REPRODUCTIVE-TRACT; MAMMARY-GLAND; MONKEY; MOUSE; MUTATION; ADULT; WNT4
AB Bisphenol A (BPA) exposure results in numerous developmental and functional abnormalities in reproductive organs in rodent models, but limited data are available regarding BPA effects in the primate uterus. To determine if maternal oral BPA exposure affects fetal uterine development in a non-human primate model, pregnant rhesus macaques carrying female fetuses were exposed orally to 400 mu g/kg BPA or vehicle control daily from gestation day (GD) 50-100 or GD100-165. Fetal uteri were collected at the completion of treatment (GD100 or GD165); tissue histology, cell proliferation, and expression of estrogen receptor alpha (ER alpha) and progesterone receptor (PR) were compared to that of controls. Gene expression analysis was conducted using rhesus macaque microarrays. There were no significant differences in histology or in the percentage of cells expressing the proliferation marker Ki-67, ER alpha, or PR in BPA-exposed uteri compared to controls at GD100 or GD165. Minimal differences in gene expression were observed between BPA-exposed and control GD100 uteri. However, at GD165, BPA-exposed uteri had significant differences in gene expression compared to controls. Several of the altered genes, including HOXA13, WNT4, and WNT5A, are critical for reproductive organ development and/or adult function. We conclude that second or third trimester BPA exposure does not significantly affect fetal uterus development based on morphological, proliferation, and steroid hormone receptor assessments. However, differences in expression of key developmental genes after third trimester exposure suggest that BPA could alter transcriptional signals influencing uterine function later in life.
C1 [Calhoun, Kathryn C.; Padilla-Banks, Elizabeth; Jefferson, Wendy N.; Williams, Carmen J.] NIEHS, Reprod Med Grp, Lab Reprod & Dev Toxicol, Res Triangle Pk, NC 27709 USA.
[Calhoun, Kathryn C.; Young, Steven L.] Univ N Carolina, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Chapel Hill, NC USA.
[Liu, Liwen; Gerrish, Kevin E.] NIEHS, Microarray Grp, Res Triangle Pk, NC 27709 USA.
[Wood, Charles E.] US EPA, Natl Hlth & Environm Effects Res Lab, Off Res & Dev, Res Triangle Pk, NC 27711 USA.
[Hunt, Patricia A.] Washington State Univ, Sch Mol Biosci, Pullman, WA 99164 USA.
[VandeVoort, Catherine A.] Univ Calif Davis, Dept Obstet & Gynecol, Davis, CA 95616 USA.
[VandeVoort, Catherine A.] Univ Calif Davis, Calif Natl Primate Res Ctr, Davis, CA 95616 USA.
RP Williams, CJ (reprint author), NIEHS, Reprod Med Grp, Lab Reprod & Dev Toxicol, POB 12233, Res Triangle Pk, NC 27709 USA.
EM williamsc5@niehs.nih.gov
RI Williams, Carmen/E-2170-2013
OI Williams, Carmen/0000-0001-6440-7086
FU National Institutes of Health, National Institutes of Environmental
Health Sciences [ES102405, ES016770, ES013527]; National Center for
Research Resources, Office of the Director to the California National
Primate Research Center [RR000169/OD011107]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Institutes of Environmental
Health Sciences [ES102405 to C.J.W.], National Institutes of Health,
National Institutes of Environmental Health Sciences
(http://www.niehs.nih.gov/) [ES016770 to C. A. V. and P. A. H. and
ES013527 to P. A. H.], and the National Center for Research Resources
(http://www.nih.gov/about/almanac/organization/NCRR.htm), Office of the
Director to the California National Primate Research Center
[RR000169/OD011107]. This manuscript was approved for publication by the
National Health and Environmental Effects Research Laboratory of the
Environmental Protection Agency but does not necessarily represent the
opinions or policy of the agency. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 43
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Z9 21
U1 2
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 JAN 23
PY 2014
VL 9
IS 1
AR e85894
DI 10.1371/journal.pone.0085894
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 297XI
UT WOS:000330288000031
PM 24465770
ER
PT J
AU Kales, SC
Nau, MM
Merchant, AS
Lipkowitz, S
AF Kales, Stephen C.
Nau, Marion M.
Merchant, Anand S.
Lipkowitz, Stanley
TI Enigma Prevents Cbl-c-Mediated Ubiquitination and Degradation of
RETMEN2A
SO PLOS ONE
LA English
DT Article
ID RECEPTOR TYROSINE KINASE; BREAST-CANCER; LIM DOMAIN; PROTEIN LIGASE;
CELL-LINE; RET; ACTIVATION; MICE; PROTOONCOGENE; SUPPRESSION
AB The Cbl proteins (Cbl, Cbl-b, and Cbl-c) are a highly conserved family of RING finger ubiquitin ligases (E3s) that function as negative regulators of tyrosine kinases in a wide variety of signal transduction pathways. In this study, we identify a new Cbl-c interacting protein, Enigma (PDLIM7). This interaction is specific to Cbl-c as Enigma fails to bind either of its closely related homologues, Cbl and Cbl-b. The binding between Enigma and Cbl-c is mediated through the LIM domains of Enigma as removal of all three LIM domains abrogates this interaction, while only LIM1 is sufficient for binding. Here we show that Cbl-c binds wild-type and MEN2A isoforms of the receptor tyrosine kinase, RET, and that Cbl-c enhances ubiquitination and degradation of activated RET. Enigma blocks Cbl-c-mediated RETMEN2A ubiquitination and degradation. Cbl-c decreased downstream ERK activation by RETMEN2A and co-expression of Enigma blocked the Cbl-c-mediated decrease in ERK activation. Enigma showed no detectable effect on Cbl-c-mediated ubiquitination of activated EGFR suggesting that this effect is specific to RET. Through mapping studies, we show that Cbl-c and Enigma bind RETMEN2A at different residues. However, binding of Enigma to RETMENA prevents Cbl-c recruitment to RETMEN2A. Consistent with these biochemical data, exploratory analyses of breast cancer patients with high expression of RET suggest that high expression of Cbl-c correlates with a good outcome, and high expression of Enigma correlates with a poor outcome. Together, these data demonstrate that Cbl-c can ubiquitinate and downregulate RETMEN2A and implicate Enigma as a positive regulator of RETMEN2A through blocking of Cbl-mediated ubiquitination and degradation.
C1 [Kales, Stephen C.; Nau, Marion M.; Lipkowitz, Stanley] NCI, Natl Inst Hlth, Ctr Canc Res, Womens Malignancies Branch, Bethesda, MD 20892 USA.
[Merchant, Anand S.] SAIC Frederick, Adv Biomed Comp Ctr, Ctr Canc Res, Bioinformat Core, Frederick, MD USA.
RP Lipkowitz, S (reprint author), NCI, Natl Inst Hlth, Ctr Canc Res, Womens Malignancies Branch, Bethesda, MD 20892 USA.
EM lipkowis@mail.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research
FX This research wassupported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 48
TC 3
Z9 3
U1 0
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JAN 23
PY 2014
VL 9
IS 1
AR e87116
DI 10.1371/journal.pone.0087116
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 297XI
UT WOS:000330288000193
PM 24466333
ER
PT J
AU Kulkarni, V
Valentin, A
Rosati, M
Alicea, C
Singh, AK
Jalah, R
Broderick, KE
Sardesai, NY
Le Gall, S
Mothe, B
Brander, C
Rolland, M
Mullins, JI
Pavlakis, GN
Felber, BK
AF Kulkarni, Viraj
Valentin, Antonio
Rosati, Margherita
Alicea, Candido
Singh, Ashish K.
Jalah, Rashmi
Broderick, Kate E.
Sardesai, Niranjan Y.
Le Gall, Sylvie
Mothe, Beatriz
Brander, Christian
Rolland, Morgane
Mullins, James I.
Pavlakis, George N.
Felber, Barbara K.
TI Altered Response Hierarchy and Increased T-Cell Breadth upon HIV-1
Conserved Element DNA Vaccination in Macaques
SO PLOS ONE
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; IMMUNE-RESPONSES; LYMPHOCYTE RESPONSES;
RHESUS-MONKEYS; TYPE-1 PROTEINS; HOST GENETICS; VIRAL LOAD; ET-AL;
VACCINES; REGIONS
AB HIV sequence diversity and potential decoy epitopes are hurdles in the development of an effective AIDS vaccine. A DNA vaccine candidate comprising of highly conserved p24(gag) elements (CE) induced robust immunity in all 10 vaccinated macaques, whereas full-length gag DNA vaccination elicited responses to these conserved elements in only 5 of 11 animals, targeting fewer CE per animal. Importantly, boosting CE-primed macaques with DNA expressing full-length p55(gag) increased both magnitude of CE responses and breadth of Gag immunity, demonstrating alteration of the hierarchy of epitope recognition in the presence of pre-existing CE-specific responses. Inclusion of a conserved element immunogen provides a novel and effective strategy to broaden responses against highly diverse pathogens by avoiding decoy epitopes, while focusing responses to critical viral elements for which few escape pathways exist.
C1 [Kulkarni, Viraj; Alicea, Candido; Jalah, Rashmi; Felber, Barbara K.] NCI, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21701 USA.
[Valentin, Antonio; Rosati, Margherita; Singh, Ashish K.; Pavlakis, George N.] NCI, Human Retrovirus Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21701 USA.
[Broderick, Kate E.; Sardesai, Niranjan Y.] Inovio Pharmaceut Inc, Blue Bell, PA USA.
[Le Gall, Sylvie] Ragon Inst MGH MIT & Harvard, Boston, MA USA.
[Mothe, Beatriz; Brander, Christian] Autonomous Univ Barcelona, IrsiCaixa AIDS Res Inst HIVACAT, Barcelona, Spain.
[Brander, Christian] ICREA, Barcelona, Spain.
[Rolland, Morgane; Mullins, James I.] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA.
[Mullins, James I.] Univ Washington, Dept Med, Seattle, WA USA.
[Mullins, James I.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA.
RP Pavlakis, GN (reprint author), NCI, Human Retrovirus Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21701 USA.
EM pavlakig@mail.nih.gov; felberb@mail.nih.gov
RI bebarta, vikhyat/K-3476-2015;
OI Brander, Christian/0000-0002-0548-5778
FU Intramural Research Program of the National Cancer Institute, National
Institutes of Health (NCI/NIH); Bill and Melinda Gates Foundation
[A39748]; University of Washington Centers for AIDS Research
Computational Biology Core [NIH P30 AI27757]; Red de Investigacion de
Sida (RIS) [RD06/04]; Instituto de Salud Carlos III (ISCIII), Madrid,
Spain; Spanish FIPSE [36-0737-09]
FX This work was funded in part by the Intramural Research Program of the
National Cancer Institute, National Institutes of Health (NCI/NIH), the
Bill and Melinda Gates Foundation (A39748) and the University of
Washington Centers for AIDS Research Computational Biology Core (NIH P30
AI27757), and was supported in part by the Red de Investigacion de Sida
(RIS) (RD06/04), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
and the Spanish FIPSE 36-0737-09. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 63
TC 21
Z9 22
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 JAN 23
PY 2014
VL 9
IS 1
AR e86254
DI 10.1371/journal.pone.0086254
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 297XI
UT WOS:000330288000074
PM 24465991
ER
PT J
AU Smith, S
Fox, J
Mejia, M
Ruangpradit, W
Saberi, A
Kim, S
Choi, Y
Oh, S
Wang, YC
Choi, K
Li, L
Hendrickson, EA
Takeda, S
Muller, M
Myung, K
AF Smith, Stephanie
Fox, Jennifer
Mejia, Marco
Ruangpradit, Wanvipa
Saberi, Alihossein
Kim, Sunmi
Choi, Yongjun
Oh, Sehyun
Wang, Yucai
Choi, Kyungho
Li, Lei
Hendrickson, Eric A.
Takeda, Shunichi
Muller, Mark
Myung, Kyungjae
TI Histone Deacetylase Inhibitors Selectively Target Homology Dependent DNA
Repair Defective Cells and Elevate Non-Homologous Endjoining Activity
SO PLOS ONE
LA English
DT Article
ID STRAND-BREAK-REPAIR; PROTEIN-KINASE; V(D)J RECOMBINATION; CATALYTIC
SUBUNIT; MAMMALIAN-CELLS; CANCER-CELLS; HUMAN ELG1; PHOSPHORYLATION;
DAMAGE; STABILITY
AB Background: We have previously used the ATAD5-luciferase high-throughput screening assay to identify genotoxic compounds with potential chemotherapeutic capabilities. The successful identification of known genotoxic agents, including the histone deacetylase inhibitor (HDACi) trichostatin A (TSA), confirmed the specificity of the screen since TSA has been widely studied for its ability to cause apoptosis in cancer cells. Because many cancers have acquired mutations in DNA damage checkpoints or repair pathways, we hypothesized that these cancers may be susceptible to treatments that target compensatory pathways. Here, we used a panel of isogenic chicken DT40 B lymphocyte mutant and human cell lines to investigate the ability of TSA to define selective pathways that promote HDACi toxicity.
Results: HDACi induced a DNA damage response and reduced viability in all repair deficient DT40 mutants although ATM-nulls were least affected. The most dramatic sensitivity was observed in mutants lacking the homology dependent repair (HDR) factor BLM or the non-homologous end-joining (NHEJ) and HDR factors, KU/RAD54, suggesting an involvement of either HDR or NHEJ in HDACi-induced cell death. To extend these findings, we measured the frequencies of HDR and NHEJ after HDACi treatment and monitored viability in human cell lines comparably deficient in HDR or NHEJ. Although no difference in HDR frequency was observed between HDACi treated and untreated cells, HDR-defective human cell lines were clearly more sensitive than wild type. Unexpectedly, cells treated with HDACis showed a significantly elevated NHEJ frequency.
Conclusions: HDACi targeting drugs induced significant increases in NHEJ activity in human cell lines but did not alter HDR frequency. Moreover, HDR is required for cellular resistance to HDACi therapy; therefore, NHEJ does not appear to be a critical axis for HDACi resistance. Rather, HDACi compounds induced DNA damage, most likely double strand breaks (DSBs), and HDR proficiency is correlated with cell survival.
C1 [Smith, Stephanie; Fox, Jennifer; Kim, Sunmi; Choi, Yongjun; Myung, Kyungjae] NHGRI, Genome Instabil Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
[Mejia, Marco; Ruangpradit, Wanvipa; Muller, Mark] Univ Cent Florida, Coll Med, Dept Mol Biol & Microbiol, Orlando, FL USA.
[Saberi, Alihossein; Kim, Sunmi; Takeda, Shunichi] Kyoto Univ, Sch Med, Dept Radiat Genet, Kyoto 6068501, Japan.
[Kim, Sunmi; Choi, Kyungho] Seoul Natl Univ, Dept Environm Hlth Sch Publ Hearth, Seoul, South Korea.
[Wang, Yucai; Li, Lei] Univ Texas MD Anderson Canc Ctr, Dept Expt Clin Oncol, Houston, TX 77030 USA.
[Li, Lei] Univ Texas MD Anderson Canc Ctr, Dept Genet, Houston, TX 77030 USA.
[Wang, Yucai] Univ Texas Houston, Grad Sch Biomed Sci, Houston, TX USA.
[Oh, Sehyun; Hendrickson, Eric A.] Univ Minnesota, Sch Med, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA.
RP Myung, K (reprint author), NHGRI, Genome Instabil Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
EM kmyung@mail.nih.gov
FU NIH [GM088351, CA154461, CA127945, CA097175, R03 MH092164-01]; UCF
College of Medicine; Ministry of Education, Culture, Sports, Science and
Technology of the Japanese Government (MEXT) [20241012]; National
Research Foundation of Korea (NRF); Ministry of Education, Science and
Technology [357-2011-D00133]; National Human Genome Research Institute
FX This research was supported by the NIH grants GM088351, CA154461 to EAH,
the NIH grants CA127945, CA097175 to LL, the UCF College of Medicine to
MTM, a grant-in-aid from the Ministry of Education, Culture, Sports,
Science and Technology of the Japanese Government (MEXT, number
20241012) to ST, the National Research Foundation of Korea (NRF) funded
by the Ministry of Education, Science and Technology (357-2011-D00133),
the intramural Research Programs of the National Human Genome Research
Institute and NIH R03 MH092164-01 to KM. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 54
TC 7
Z9 7
U1 2
U2 13
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 JAN 23
PY 2014
VL 9
IS 1
AR e87203
DI 10.1371/journal.pone.0087203
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 297XI
UT WOS:000330288000198
PM 24466340
ER
PT J
AU Yu, DL
Pi, BR
Chen, Y
Wang, YF
Ruan, Z
Otto, M
Yu, YS
AF Yu, Dongliang
Pi, Borui
Chen, Yan
Wang, Yanfei
Ruan, Zhi
Otto, Michael
Yu, Yunsong
TI Characterization of the Staphylococcal Cassette Chromosome Composite
Island of Staphylococcus haemolyticus SH32, a Methicillin-Resistant
Clinical Isolate from China
SO PLOS ONE
LA English
DT Article
ID HORIZONTAL GENE-TRANSFER; MEC SCCMEC; AUREUS; IDENTIFICATION; VIRULENCE;
SEQUENCE; STRAINS; GENOME
AB Staphylococcal cassette chromosome (SCC) elements contribute considerably to virulence and resistance to antibiotic agents in staphylococci. SCC elements in coagulase-negative staphylococci (CoNS) are highly diverse and there is evidence suggesting that they serve as a reservoir for antibiotic resistance genes in methicillin-resistant Staphylococcus aureus (MRSA). However, only a small number of SCC elements have been characterized in CoNS and their exact roles in the emergence and evolution of MRSA remain to be demonstrated. Here, we determined the structure of an SCC composite island (CISH32) found in the clinical Staphylococcus haemolyticus isolate SH32 by whole-genome DNA sequencing. CISH32 was 48 kb in length and mainly composed of two imperfect SCC elements, namely (i) a Psi SCCmec(SH32) part containing a class C1 mec gene complex but lacking ccr genes and (ii) a SCCSH32 part with a ccrA5B3 gene complex but lacking mec genes. In addition, CISH32 contained a type III restriction-modification system and several resistance loci, for example genes conferring resistance to cadmium and arsenic. Psi SCCmec(SH32) is almost entirely identical to a pseudo SCCmec element found in S. haemolyticus WCH1 and shares pronounced sequence similarity to a Psi SCCmec element of S. haemolyticus JCSC1435. However, staphylococci other than S. haemolyticus, including S. aureus and S. epidermidis, contain homologs of SCCSH32 that are more similar to SCCSH32 than those elements found in S. haemolyticus, suggesting that CISH32 of S. haemolyticus SH32 was assembled in recent evolutionary events. Moreover, the composite structure of CISH32 indicates that the detection of class C1 mec and ccrA5B3 gene complexes in S. haemolyticus does not always indicate the existence of a UT9-type SCCmec element, which has remained questionable.
C1 [Yu, Dongliang] Hangzhou Normal Univ, Inst Dev & Regenerat Biol, Hangzhou, Zhejiang, Peoples R China.
[Yu, Dongliang; Pi, Borui; Chen, Yan; Wang, Yanfei; Ruan, Zhi; Yu, Yunsong] Zhejiang Univ, Coll Med, Sir Run Run Shaw Hosp, Dept Infect Dis, Hangzhou 310003, Zhejiang, Peoples R China.
[Chen, Yan; Otto, Michael] NIAID, NIH, Bethesda, MD 20892 USA.
RP Otto, M (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM motto@niaid.nih.gov; yvys119@163.com
RI Ruan, Zhi/P-3987-2015;
OI Ruan, Zhi/0000-0001-8648-4592; Otto, Michael/0000-0002-2222-4115
FU National Natural Science Foundation of China [NSFC81201327]; Ministry of
Health of the People's Republic of China [201002021]; Science Technology
Department of Zhejiang Province [2008C13029-1]; Intramural Research
Program of the National Institute of Allergy and Infectious Diseases
(NIAID), U.S. National Institutes of Health (NIH)
FX This work was supported by the National Natural Science Foundation of
China (no. NSFC81201327), the Ministry of Health of the People's
Republic of China (no. 201002021), the Science Technology Department of
Zhejiang Province (no. 2008C13029-1), and the Intramural Research
Program of the National Institute of Allergy and Infectious Diseases
(NIAID), U.S. National Institutes of Health (NIH). The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 25
TC 4
Z9 4
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 JAN 23
PY 2014
VL 9
IS 1
AR e87346
DI 10.1371/journal.pone.0087346
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 297XI
UT WOS:000330288000204
PM 24466348
ER
PT J
AU Luci, DK
Jameson, JB
Yasgar, A
Diaz, G
Joshi, N
Kantz, A
Markham, K
Perry, S
Kuhn, N
Yeung, J
Kerns, EH
Schultz, L
Holinstat, M
Nadler, JL
Taylor-Fishwick, DA
Jadhav, A
Simeonov, A
Holman, TR
Maloney, DJ
AF Luci, Diane K.
Jameson, J. Brian, II
Yasgar, Adam
Diaz, Giovanni
Joshi, Netra
Kantz, Auric
Markham, Kate
Perry, Steve
Kuhn, Norine
Yeung, Jennifer
Kerns, Edward H.
Schultz, Lena
Holinstat, Michael
Nadler, Jerry L.
Taylor-Fishwick, David A.
Jadhav, Ajit
Simeonov, Anton
Holman, Theodore R.
Maloney, David J.
TI Synthesis and Structure-Activity Relationship Studies of
4-((2-Hydroxy-3-methoxybenzyl)amino)benzenesulfonamide Derivatives as
Potent and Selective Inhibitors of 12-Lipoxygenase
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID PLATELET-TYPE 12-LIPOXYGENASE; HUMAN LIPOXYGENASE INHIBITORS; 12-HUMAN
LIPOXYGENASE; BIOLOGICAL-ACTIVITIES; HUMAN 15-LIPOXYGENASE; POSSIBLE
INVOLVEMENT; DEFICIENT MICE; ACID; 12/15-LIPOXYGENASE; ACTIVATION
AB Human lipoxygenases (LOXs) are a family of iron-containing enzymes which catalyze the oxidation of polyunsaturated fatty acids to provide the corresponding bioactive hydroxyeicosatetraenoic acid (HETE) metabolites. These eicosanoid signaling molecules are involved in a number of physiologic responses such as platelet aggregation, inflammation, and cell proliferation. Our group has taken a particular interest in platelet-type 12-(S)-LOX (12-LOX) because of its demonstrated role in skin diseases, diabetes, platelet hemostasis, thrombosis, and cancer. Herein, we report the identification and medicinal chemistry, optimization of a 4-((2-hydroxy-3-methoxybenzyl)amino)benzenesulfonamide-based scaffold. Top compounds, exemplified by 35 and 36, display nM potency. against 12-LOX, excellent selectivity over related lipoxygenases and cyclooxygenases, and possess favorable ADME properties. In addition, both compounds inhibit PAR-4 induced aggregation and calcium mobilization in human platelets and reduce 12-HETE in beta-cells.
C1 [Luci, Diane K.; Yasgar, Adam; Kerns, Edward H.; Schultz, Lena; Jadhav, Ajit; Simeonov, Anton; Maloney, David J.] NIH, Natl Ctr Adv Translat Sci, Rockville, MD 20852 USA.
[Jameson, J. Brian, II; Diaz, Giovanni; Joshi, Netra; Kantz, Auric; Markham, Kate; Perry, Steve; Holman, Theodore R.] Univ Calif Santa Cruz, Dept Chem & Biochem, Santa Cruz, CA 95064 USA.
[Kuhn, Norine; Nadler, Jerry L.; Taylor-Fishwick, David A.] Eastern Virginia Med Sch, Strelitz Diabet Ctr, Norfolk, VA 23501 USA.
[Yeung, Jennifer; Holinstat, Michael] Thomas Jefferson Univ, Dept Med, Cardeza Fdn Hematol Res, Philadelphia, PA 19107 USA.
RP Maloney, DJ (reprint author), NIH, Natl Ctr Adv Translat Sci, Rockville, MD 20852 USA.
EM Holman@ucsc.edu; maloneyd@mail.nih.gov
OI Taylor-Fishwick, David/0000-0002-6720-7482
FU National Center for Advancing Translational Sciences; Molecular
Libraries Initiative of the National Institutes of Health Roadmap for
Medical Research [U54MH084681, R03 MH081283]; National Institute of
Health [R01 GM56062, HL114405, GM105671]; NIH [S10-RR20939, RO1
HL112605]; California Institute for Quantitative Biosciences; Cardeza
Foundation for Hematologic Research; Juvenile Diabetes Research
Foundation
FX D.K.L., A.Y., E.H.K., L.S., A.J., A.S., and D.J.M. were supported the
intramural research program of the National Center for Advancing
Translational Sciences and the Molecular Libraries Initiative of the
National Institutes of Health Roadmap for Medical Research
(U54MH084681). Financial support was from the National Institute of
Health grants R01 GM56062 (T.R.H.), HL114405 (M.H.), GM105671 (M.H.),
and the Molecular Libraries Initiative of the National Institutes of
Health Roadmap for Medical Research (R03 MH081283 (T.R.H.)). Additional
financial support was from NIH (S10-RR20939 (T.R.H.)), the California
Institute for Quantitative Biosciences for the UCSC MS Facility
(T.R.H.), and the Cardeza Foundation for Hematologic Research (M.H.).
Human islets were provided by the Integrated Islet Distribution Program
(IIDP). Additional support was provided by the Juvenile Diabetes
Research Foundation to J.L.N., D.T.F., and T.R.H. and NIH RO1 HL112605
to J.L.N. We thank Sam Michael and Richard Jones for automation support,
Paul Shinn and Danielle van Leer for the assistance with compound
management, William Leister, Heather Baker, Elizabeth Fernandez, and
Christopher Leclair for analytical chemistry and purification support,
and Kimloan Nguyen for in vitro ADME data.
NR 63
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U1 2
U2 14
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
EI 1520-4804
J9 J MED CHEM
JI J. Med. Chem.
PD JAN 23
PY 2014
VL 57
IS 2
BP 495
EP 506
DI 10.1021/jm4016476
PG 12
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 297JU
UT WOS:000330252500018
PM 24393039
ER
PT J
AU Roederer, M
Keele, BF
Schmidt, SD
Mason, RD
Welles, HC
Fischer, W
Labranche, C
Foulds, KE
Louder, MK
Yang, ZY
Todd, JPM
Buzby, AP
Mach, LV
Shen, L
Seaton, KE
Ward, BM
Bailer, RT
Gottardo, R
Gu, WJ
Ferrari, G
Alam, SM
Denny, TN
Montefiori, DC
Tomaras, GD
Korber, BT
Nason, MC
Seder, RA
Koup, RA
Letvin, NL
Rao, SS
Nabel, GJ
Mascola, JR
AF Roederer, Mario
Keele, Brandon F.
Schmidt, Stephen D.
Mason, Rosemarie D.
Welles, Hugh C.
Fischer, Will
Labranche, Celia
Foulds, Kathryn E.
Louder, Mark K.
Yang, Zhi-Yong
Todd, John-Paul M.
Buzby, Adam P.
Mach, Linh V.
Shen, Ling
Seaton, Kelly E.
Ward, Brandy M.
Bailer, Robert T.
Gottardo, Raphael
Gu, Wenjuan
Ferrari, Guido
Alam, S. Munir
Denny, Thomas N.
Montefiori, David C.
Tomaras, Georgia D.
Korber, Bette T.
Nason, Martha C.
Seder, Robert A.
Koup, Richard A.
Letvin, Norman L.
Rao, Srinivas S.
Nabel, Gary J.
Mascola, John R.
TI Immunological and virological mechanisms of vaccine-mediated protection
against SIV and HIV
SO NATURE
LA English
DT Article
ID SIMIAN IMMUNODEFICIENCY VIRUS; DOSE CHALLENGE EXPERIMENTS; NEUTRALIZING
ANTIBODIES; RHESUS MACAQUES; CELL RESPONSES; EFFICACY TRIAL; INFECTION;
BINDING; SIVSME660; PREVENTION
AB A major challenge for the development of a highly effective AIDS vaccine is the identification of mechanisms of protective immunity. To address this question, we used a nonhuman primate challenge model with simian immunodeficiency virus (SIV). We show that antibodies to the SIV envelope are necessary and sufficient to prevent infection. Moreover, sequencing of viruses from breakthrough infections revealed selective pressure against neutralization-sensitive viruses; we identified a two-amino-acid signature that alters antigenicity and confers neutralization resistance. A similar signature confers resistance of human immunodeficiency virus (HIV)-1 to neutralization by monoclonal antibodies against variable regions 1 and 2 (V1V2), suggesting that SIV and HIV share a fundamental mechanism of immune escape from vaccine-elicited or naturally elicited antibodies. These analyses provide insight into the limited efficacy seen in HIV vaccine trials.
C1 [Roederer, Mario; Schmidt, Stephen D.; Mason, Rosemarie D.; Welles, Hugh C.; Foulds, Kathryn E.; Louder, Mark K.; Yang, Zhi-Yong; Todd, John-Paul M.; Bailer, Robert T.; Seder, Robert A.; Koup, Richard A.; Rao, Srinivas S.; Nabel, Gary J.; Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Keele, Brandon F.] NIH, SAIC Frederick, Frederick Natl Lab, Frederick, MD 21702 USA.
[Welles, Hugh C.] George Washington Univ, Washington, DC 20052 USA.
[Fischer, Will; Korber, Bette T.] Los Alamos Natl Labs, Los Alamos, NM 87545 USA.
[Labranche, Celia; Ward, Brandy M.; Ferrari, Guido; Montefiori, David C.] Duke Univ, Dept Surg, Durham, NC 27710 USA.
[Buzby, Adam P.; Mach, Linh V.; Shen, Ling; Letvin, Norman L.] Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02115 USA.
[Seaton, Kelly E.; Alam, S. Munir; Denny, Thomas N.; Tomaras, Georgia D.] Duke Univ, Human Vaccine Inst, Durham, NC 27710 USA.
[Gottardo, Raphael] Fred Hutchison Canc Res Ctr, Seattle, WA 98109 USA.
[Gu, Wenjuan; Nason, Martha C.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
RP Roederer, M (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM Roederer@NIH.gov
RI Schmidt, Stephen/B-5398-2012; Ferrari, Guido/A-6088-2015; Tomaras,
Georgia/J-5041-2016;
OI Denny, Thomas/0000-0002-7364-8276; Welles, Hugh/0000-0002-3336-1203;
Fischer, Will/0000-0003-4579-4062; Korber, Bette/0000-0002-2026-5757
FU Intramural Research Program of the Vaccine Research Center, NIAID, NIH;
NIH [HHSN261200800001E, HHSN27201100016C, AI100645]; Bill and Melinda
Gates Foundation [OPP1032317]
FX We thank the following individuals: W. Shi, L. Wu, S.-Y. Ko, L. Wang and
W.-P. Kong for immunogen construction; M. M. Donaldson, S.-F. Kao, D.
Quinn, J. Owuor, K. Denison, H. Balachandran, C. Luedemann, W. T.
Williams, G. Overman, A. Deal, C. Brinkley and L. Racz for technical
assistance with immunology assays; A. Ault for assistance managing NHP
studies; S. O'Connor for deep-sequencing data; M. Seaman for providing
plasmids encoding E660 envelopes; F. McCutchan, J. Overbaugh and J. Kim
for HIV-1 strains; and P. Gilbert for advice with using the Aalen and
Johansen model. This work was supported by the Intramural Research
Program of the Vaccine Research Center, NIAID, NIH; by NIH contracts
HHSN261200800001E (B. F. K., W. G.) and HHSN27201100016C (D. C. M.); by
NIH grant AI100645 (B. T. K., W. F.); and by the Bill and Melinda Gates
Foundation grant OPP1032317.
NR 39
TC 65
Z9 65
U1 3
U2 48
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 JAN 23
PY 2014
VL 505
IS 7484
BP 502
EP +
DI 10.1038/nature12893
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 293SW
UT WOS:000329995000030
PM 24352234
ER
PT J
AU Cruchaga, C
Karch, CM
Jin, SC
Benitez, BA
Cai, YF
Guerreiro, R
Harari, O
Norton, J
Budde, J
Bertelsen, S
Jeng, AT
Cooper, B
Skorupa, T
Carrell, D
Levitch, D
Hsu, S
Choi, J
Ryten, M
Sassi, C
Bras, J
Gibbs, JR
Hernandez, DG
Lupton, MK
Powell, J
Forabosco, P
Ridge, PG
Corcoran, CD
Tschanz, JT
Norton, MC
Munger, RG
Schmutz, C
Leary, M
Demirci, FY
Bamne, MN
Wang, XB
Lopez, OL
Ganguli, M
Medway, C
Turton, J
Lord, J
Braae, A
Barber, I
Brown, K
Pastor, P
Lorenzo-Betancor, O
Brkanac, Z
Scott, E
Topol, E
Morgan, K
Rogaeva, E
Singleton, AB
Hardy, J
Kamboh, MI
St George-Hyslop, P
Cairns, N
Morris, JC
Kauwe, JSK
Goate, AM
AF Cruchaga, Carlos
Karch, Celeste M.
Jin, Sheng Chih
Benitez, Bruno A.
Cai, Yefei
Guerreiro, Rita
Harari, Oscar
Norton, Joanne
Budde, John
Bertelsen, Sarah
Jeng, Amanda T.
Cooper, Breanna
Skorupa, Tara
Carrell, David
Levitch, Denise
Hsu, Simon
Choi, Jiyoon
Ryten, Mina
Sassi, Celeste
Bras, Jose
Gibbs, J. Raphael
Hernandez, Dena G.
Lupton, Michelle K.
Powell, John
Forabosco, Paola
Ridge, Perry G.
Corcoran, Christopher D.
Tschanz, Joann T.
Norton, Maria C.
Munger, Ronald G.
Schmutz, Cameron
Leary, Maegan
Demirci, F. Yesim
Bamne, Mikhil N.
Wang, Xingbin
Lopez, Oscar L.
Ganguli, Mary
Medway, Christopher
Turton, James
Lord, Jenny
Braae, Anne
Barber, Imelda
Brown, Kristelle
Pastor, Pau
Lorenzo-Betancor, Oswaldo
Brkanac, Zoran
Scott, Erick
Topol, Eric
Morgan, Kevin
Rogaeva, Ekaterina
Singleton, Andrew B.
Hardy, John
Kamboh, M. Ilyas
St George-Hyslop, Peter
Cairns, Nigel
Morris, John C.
Kauwe, John S. K.
Goate, Alison M.
CA UKBEC
Alzheimers Res UK ARUK Consortium
TI Rare coding variants in the phospholipase D3 gene confer risk for
Alzheimer's disease
SO NATURE
LA English
DT Article
ID NETWORK ANALYSIS; EXPRESSION; ASSOCIATION; AGE; PROTEOLYSIS; DIAGNOSIS;
INSIGHTS; DEMENTIA; MUTATION; NEURONS
AB Genome-wide association studies (GWAS) have identified several risk variants for late-onset Alzheimer's disease (LOAD)(1,2). These common variants have replicable but small effects on LOAD risk and generally do not have obvious functional effects. Low-frequency coding variants, not detected by GWAS, are predicted to include functional variants with larger effects on risk. To identify low-frequency coding variants with large effects on LOAD risk, we carried out whole-exome sequencing (WES) in 14 large LOAD families and follow-up analyses of the candidate variants in several large LOAD case-control data sets. A rare variant in PLD3 (phospholipase D3; Val232Met) segregated with disease status in two independent families and doubled risk for Alzheimer's disease in seven independent case-control series with a total of more than 11,000 cases and controls of European descent. Gene-based burden analyses in 4,387 cases and controls of European descent and 302 African American cases and controls, with complete sequence data for PLD3, reveal that several variants in this gene increase risk for Alzheimer's disease in both populations. PLD3 is highly expressed in brain regions that are vulnerable to Alzheimer's disease pathology, including hippocampus and cortex, and is expressed at significantly lower levels in neurons from Alzheimer's disease brains compared to control brains. Overexpression of PLD3 leads to a significant decrease in intracellular amyloid-beta precursor protein (APP) and extracellular A beta 42 and A beta 40 (the 42- and 40-residue isoforms of the amyloid-beta peptide), and knockdown of PLD3 leads to a significant increase in extracellular A beta 42 and A beta 40. Together, our genetic and functional data indicate that carriers of PLD3 coding variants have a twofold increased risk for LOAD and that PLD3 influences APP processing. This study provides an example of how densely affected families may help to identify rare variants with large effects on risk for disease or other complex traits.
C1 [Cruchaga, Carlos; Karch, Celeste M.; Jin, Sheng Chih; Benitez, Bruno A.; Cai, Yefei; Harari, Oscar; Norton, Joanne; Budde, John; Bertelsen, Sarah; Jeng, Amanda T.; Cooper, Breanna; Skorupa, Tara; Carrell, David; Levitch, Denise; Hsu, Simon; Choi, Jiyoon; Goate, Alison M.] Washington Univ, Dept Psychiat, St Louis, MO 63110 USA.
[Cruchaga, Carlos; Karch, Celeste M.; Cairns, Nigel; Goate, Alison M.] Washington Univ, Hope Ctr Program Prot Aggregat & Neurodegenerat, St Louis, MO 63110 USA.
[Guerreiro, Rita; Ryten, Mina; Sassi, Celeste; Bras, Jose; Gibbs, J. Raphael; Hernandez, Dena G.; Hardy, John] UCL Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England.
[Guerreiro, Rita; Sassi, Celeste; Gibbs, J. Raphael; Hernandez, Dena G.; Singleton, Andrew B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Lupton, Michelle K.; Powell, John] Kings Coll London, Inst Psychiat, London SE5 8AF, England.
[Lupton, Michelle K.] QIMR Berghofer Med Res Inst, Herston, Qld 4006, Australia.
[Forabosco, Paola] CNR, Ist Genet Popolaz, I-07100 Sassari, Italy.
[Ridge, Perry G.; Schmutz, Cameron; Leary, Maegan; Kauwe, John S. K.] Brigham Young Univ, Dept Biol, Provo, UT 84602 USA.
[Corcoran, Christopher D.] Utah State Univ, Dept Math & Stat, Logan, UT 84322 USA.
[Corcoran, Christopher D.; Tschanz, Joann T.; Norton, Maria C.] Utah State Univ, Ctr Epidemiol Studies, Logan, UT 84322 USA.
[Tschanz, Joann T.; Norton, Maria C.] Utah State Univ, Dept Psychol, Logan, UT 84322 USA.
[Norton, Maria C.; Munger, Ronald G.] Utah State Univ, Dept Family Consumer & Human Dev, Logan, UT 84322 USA.
[Munger, Ronald G.] Utah State Univ, Dept Nutr Dietet & Food Sci, Logan, UT 84322 USA.
[Demirci, F. Yesim; Bamne, Mikhil N.; Wang, Xingbin; Kamboh, M. Ilyas] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA 15261 USA.
[Lopez, Oscar L.; Kamboh, M. Ilyas] Univ Pittsburgh, Alzheimers Dis Res Ctr, Pittsburgh, PA 15261 USA.
[Lopez, Oscar L.; Kamboh, M. Ilyas] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15261 USA.
[Ganguli, Mary] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15261 USA.
[Medway, Christopher; Turton, James; Lord, Jenny; Braae, Anne; Barber, Imelda; Brown, Kristelle; Morgan, Kevin] Univ Nottingham, Sch Mol Med Sci, Queens Med Ctr, Nottingham NG7 2UH, England.
[Pastor, Pau; Lorenzo-Betancor, Oswaldo] Univ Navarra, Ctr Appl Med Res, Neurogenet Lab, Div Neurosci, Navarra 31008, Spain.
[Pastor, Pau] Univ Navarra, Sch Med, Clin Univ Navarra, Dept Neurol, Pamplona 31008, Spain.
[Pastor, Pau] Inst Salud Carlos III, CIBERNED, Madrid, Spain.
[Brkanac, Zoran] Univ Washington, Seattle, WA 98104 USA.
[Scott, Erick; Topol, Eric] Scripps Res Inst, La Jolla, CA 92037 USA.
[Rogaeva, Ekaterina; St George-Hyslop, Peter] Univ Toronto, Tanz Ctr Res Neurodegenerat Dis, Toronto, ON M5T 2S8, Canada.
[St George-Hyslop, Peter] Univ Cambridge, Cambridge Inst Med Res, Cambridge CB2 0XY, England.
[St George-Hyslop, Peter] Univ Cambridge, Dept Clin Neurosci, Cambridge CB2 0XY, England.
[Cairns, Nigel; Morris, John C.] Washington Univ, St Louis, MO 63110 USA.
[Morris, John C.; Goate, Alison M.] Washington Univ, Dept Neurol, St Louis, MO 63110 USA.
[Morris, John C.; Goate, Alison M.] Washington Univ, Knight ADRC, St Louis, MO 63110 USA.
[Goate, Alison M.] Washington Univ, Dept Genet, St Louis, MO 63110 USA.
RP Cruchaga, C (reprint author), Washington Univ, Dept Psychiat, 425 South Euclid Ave, St Louis, MO 63110 USA.
EM ccruchaga@wustl.edu
RI Hardy, John/C-2451-2009; Singleton, Andrew/C-3010-2009; Benitez,
Bruno/E-7116-2014; Powell, John/G-4412-2011; Weale, Michael/F-2587-2010;
Bras, Jose/A-1428-2011; Pastor, Pau/C-9834-2009; Pickering-Brown,
Stuart/D-4008-2009; MORAN, CATHERINE/C-9539-2015; Guerreiro,
Rita/A-1327-2011; Trabzuni, Daniah/C-4034-2012;
OI Topol, Eric/0000-0002-1478-4729; Benitez, Bruno/0000-0002-2699-3878;
Powell, John/0000-0001-6124-439X; Weale, Michael/0000-0003-4593-1186;
Pastor, Pau/0000-0002-7493-8777; Pickering-Brown,
Stuart/0000-0003-1561-6054; Trabzuni, Daniah/0000-0003-4826-9570; Bras,
Jose/0000-0001-8186-0333; Demirci, F. Yesim/0000-0001-6907-9843; Kamboh,
M. Ilyas/0000-0002-3453-1438; Cruchaga, Carlos/0000-0002-0276-2899;
Karch, Celeste/0000-0002-6854-5547; Todd, Stephen/0000-0002-2312-9195
FU National Institutes of Health [P30-NS069329, R01-AG044546, R01-AG035083,
RO1-AG11380, RO1-AG18712, RO1-AG21136, R01-AG042611]; Alzheimer
Association [NIRG-11-200110]; Barnes Jewish Foundation; American
Federation for Aging Research; BrightFocus Foundation Alzheimer's
Disease Research Grant [A2013359S]; Genentech; Pfizer; NIH [P50 AG05681,
P01 AG03991, P01 AG026276, R01039700, AG041718, AG030653, AG005133,
AG07562, AG023652]; National Institute on Aging, National Institutes of
Health, Department of Health and Human Services [ZO1 AG000950-11];
Alzheimer's Association [MNIRG-11-205368]; Alzheimer's Research UK
(ARUK); NINDS [ZO1 AG000950-10]; Wellcome Trust/MRC [WT089698]; Big
Lottery; ARUK; ASvia ABBUK Ltd.; NIHR Queen Square Dementia BRU; BRC
NIHR; Canadian Institutes of Health Research; Wellcome Trust; Medical
Research Council; National Institute of Health Research; Ontario
Research Fund; Alzheimer Society of Ontario; UK Medical Research Council
through the MRC Sudden Death Brain Bank; Department of Health of the
Government of Navarra, Spain [13085, 3/2008]; UTE project FIMA, Spain;
NIA [R01AG21136]; [U24AG21886]; [U24: 5U24AG026395]; [1R01AG041797];
[G0901254]; [G0802462]
FX We thank M. Frohman for providing us with PLD1- and PLD2-WT constructs
as well as constructs for the inactive mutations in these genes. This
work was supported by grants from the National Institutes of Health
(P30-NS069329, R01-AG044546 and R01-AG035083), the Alzheimer Association
(NIRG-11-200110) and Barnes Jewish Foundation. This research was
conducted while C.C. was a recipient of a New Investigator Award in
Alzheimer's Disease from the American Federation for Aging Research.
C.C. is a recipient of a BrightFocus Foundation Alzheimer's Disease
Research Grant (A2013359S). Sequencing of some of the families included
in this study was supported by Genentech and Pfizer. The recruitment and
clinical characterization of research participants at Washington
University were supported by NIH P50 AG05681, P01 AG03991 and P01
AG026276. This work was supported in part by the Intramural Research
Program of the National Institute on Aging, National Institutes of
Health, Department of Health and Human Services, project ZO1
AG000950-11. Samples from the National Cell Repository for Alzheimer's
Disease (NCRAD) and NIA-LOAD, which receives government support under a
cooperative agreement (U24AG21886; U24: 5U24AG026395 and 1R01AG041797),
were used in this study. We thank our contributors, including the
Alzheimer's Disease Centers, that collected samples used in this study,
as well as participants and their families, whose help and participation
made this work possible. The Cache County Study is supported by National
Institutes of Health, RO1-AG11380, RO1-AG18712 and RO1-AG21136.
Genotyping and analysis conducted at Brigham Young University was funded
by grants from the National Institutes of Health R01-AG042611 and the
Alzheimer's Association (MNIRG-11-205368) to J.S.K.K. The sequencing at
University of Washington was supported by NIH R01039700 (Z.B.). The
sequencing for the NIA-UK samples was supported by the Alzheimer's
Research UK (ARUK), by an anonymous donor, by the NINDS (ZO1
AG000950-10), by the Wellcome Trust/MRC Joint Call in Neurodegeneration
award (WT089698) to the UK Parkinson's Disease Consortium (UKPDC), by
the Big Lottery (to K.M.) and by a fellowship from ARUK to R.G; Some
samples and pathological diagnoses were provided by the MRC London
Neurodegenerative Diseases Brain Bank and the Manchester Brain Bank from
Brains for Dementia Research, jointly funded from ARUK and ASvia ABBUK
Ltd. This work was also supported by the NIHR Queen Square Dementia BRU
and BRC NIHR grant mechanisms. The sample recruitment and genetic
studies at University of Pittsburgh are funded by NIH grants AG041718,
AG030653, AG005133, AG07562 and AG023652. The Toronto sample studies are
funded by Canadian Institutes of Health Research, Wellcome Trust,
Medical Research Council, National Institute of Health, National
Institute of Health Research, Ontario Research Fund and Alzheimer
Society of Ontario (to P.S.G.-H.). The Nottingham Laboratory (K.M.) is
funded by ARUK and Big Lottery. ARUK is supported by the UK Medical
Research Council through the MRC Sudden Death Brain Bank (C.S.) and by a
Project Grant (G0901254) and Training Fellowship (G0802462 to M.R.).
P.P. receives funds from the Department of Health of the Government of
Navarra, Spain (13085 and 3/2008) and from the UTE project FIMA, Spain.
J.T.T. receives funds from the NIA (R01AG21136).
NR 47
TC 140
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U1 7
U2 79
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 JAN 23
PY 2014
VL 505
IS 7484
BP 550
EP +
DI 10.1038/nature12825
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 293SW
UT WOS:000329995000040
PM 24336208
ER
PT J
AU Ananworanich, J
Bunupuradah, T
Apornpong, T
Kosalaraksa, P
Hansudewechakul, R
Kanjanavanit, S
Ngampiyaskul, C
Wongsawat, J
Luesomboon, W
Nicole, NGH
Jaimulwong, T
Kerr, SJ
Brouwers, P
Shearer, WT
Puthanakit, T
AF Ananworanich, Jintanat
Bunupuradah, Torsak
Apornpong, Tanakorn
Kosalaraksa, Pope
Hansudewechakul, Rawiwan
Kanjanavanit, Suparat
Ngampiyaskul, Chaiwat
Wongsawat, Jurai
Luesomboon, Wicharn
Nicole Ngo-Giang-Huong
Jaimulwong, Tanyathip
Kerr, Stephen J.
Brouwers, Pim
Shearer, William T.
Puthanakit, Thanyawee
CA PREDICT Study Grp
TI Association between lymphocyte and monocyte subsets and cognition in
children with HIV
SO AIDS RESEARCH AND THERAPY
LA English
DT Article
DE Children; HIV; Lymphocytes; Monocytes; Cognition
ID INFECTED CHILDREN; NEURODEVELOPMENTAL OUTCOMES; ANTIRETROVIRAL THERAPY;
BLOOD; AGE
AB Background: This study assesses the relationships between lymphocyte and monocyte subsets and intelligence quotient (IQ) scores in antiretroviral therapy (ART)-naive, HIV-infected Thai children without advanced HIV disease.
Findings: Sixty-seven ART-naive Thai children with CD4 between 15-24% underwent cognitive testing by Weschler intelligence scale and had 13 cell subsets performed by flow cytometry including naive, memory and activated subsets of CD4+ and CD8+ T cells, activated and perivascular monocytes and B cells. Regression modelling with log(10) cell count and cell percentage transformation was performed. Median age (IQR) was 9 (7-10) years, 33% were male, CDC stages N:A:B were 1: 67: 31%, median CD4% and count (IQR) were 21 (18-24)%, 597 (424-801) cells/mm(3) and HIV RNA (IQR) was 4.6 (4.1-4.9) log(10) copies/ml. Most (82%) lived at home, 45% had a biological parent as their primary caregiver, and 26 (49%) had low family income. The mean (SD) scores were 75 (13) for full scale IQ (FIQ), 73 (12) for verbal IQ (VIQ) and 80 (14) for performance IQ (PIQ). Adjusted multivariate regression analysis showed significant negative associations between B cell counts and FIQ, VIQ and PIQ (p < 0.01 for all); similar associations were found for B cell percentages (p < 0.05 for all).
Conclusions: High B cell counts and percentages were strongly associated with poorer FIQ, VIQ and PIQ scores. Prospective, long-term assessment of cell subsets and determination of relevant B cell subpopulations could help further elucidate associations between lymphocyte subsets and neurocognitive development.
C1 [Ananworanich, Jintanat; Bunupuradah, Torsak; Apornpong, Tanakorn; Jaimulwong, Tanyathip; Kerr, Stephen J.; Puthanakit, Thanyawee] Thai Red Cross AIDS Res Ctr, HIV NAT, Bangkok 10330, Thailand.
[Ananworanich, Jintanat] Thai Red Cross AIDS Res Ctr, SEARCH, Bangkok 10330, Thailand.
[Ananworanich, Jintanat] Chulalongkorn Univ, Fac Med, Dept Med, Bangkok 10330, Thailand.
[Kosalaraksa, Pope] Khon Kaen Univ, Srinagarind Hosp, Khon Kaen, Thailand.
[Hansudewechakul, Rawiwan] Chiangrai Prachanukroh Hosp, Chiang Rai, Thailand.
[Kanjanavanit, Suparat] Nakornping Hosp, Chiang Mai, Thailand.
[Ngampiyaskul, Chaiwat] Prapokklao Hosp, Chanthaburi, Thailand.
[Wongsawat, Jurai] Bamrasnaradura Infect Dis Inst, Nonthaburi, Thailand.
[Luesomboon, Wicharn] Queen SavangVadhana Mem Hosp, Chon Buri, Thailand.
[Nicole Ngo-Giang-Huong] Inst Rech Dev IRD U174, Program HIV Prevent & Treatment, Chiang Mai, Thailand.
[Ananworanich, Jintanat; Kerr, Stephen J.] Univ New S Wales, Kirby Inst Infect & Immun Soc, Sydney, NSW, Australia.
[Brouwers, Pim] NIMH, Div AIDS Res, Bethesda, MD 20892 USA.
[Shearer, William T.] Baylor Coll Med, Houston, TX 77030 USA.
[Puthanakit, Thanyawee] Chulalongkorn Univ, Fac Med, Dept Pediat, Bangkok 10330, Thailand.
RP Ananworanich, J (reprint author), Thai Red Cross AIDS Res Ctr, HIV NAT, 104 Rajdumri Rd, Bangkok 10330, Thailand.
EM jintanat.a@hivnat.org
OI Mofenson, Lynne/0000-0002-2818-9808; Ngo-Giang-Huong,
Nicole/0000-0001-8950-3234
FU National Institute of Allergy and Infectious Diseases of the National
Institute of Health [U19 AI53741, 1R01AI075408-0]; Eunice Kennedy
Shriver National Institute of Child Health and Human Development;
National Institute of Mental Health
FX We thank The Immunology Research Fund, Texas Children's Hospital,
Houston, TX, USA for the gift of monoclonal antibody reagents for the
pilot study. The work was supported by grants from the National
Institute of Allergy and Infectious Diseases of the National Institute
of Health through the Comprehensive International Program of Research on
AIDS Network (U19 AI53741) and 1R01AI075408-0; co-funded by the Eunice
Kennedy Shriver National Institute of Child Health and Human Development
and the National Institute of Mental Health. The views in this report do
not necessary reflect the views of the National Institutes of Health or
U.S. Department of Health and Human Services.
NR 13
TC 0
Z9 0
U1 1
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-6405
J9 AIDS RES THER
JI Aids Res. Ther.
PD JAN 22
PY 2014
VL 11
AR 7
DI 10.1186/1742-6405-11-7
PG 5
WC Infectious Diseases
SC Infectious Diseases
GA AB8FZ
UT WOS:000332026900003
PM 24450991
ER
PT J
AU Gieseck, RL
Hannan, NRF
Bort, R
Hanley, NA
Drake, RAL
Cameron, GWW
Wynn, TA
Vallier, L
AF Gieseck, Richard L., III
Hannan, Nicholas R. F.
Bort, Roque
Hanley, Neil A.
Drake, Rosemary A. L.
Cameron, Grant W. W.
Wynn, Thomas A.
Vallier, Ludovic
TI Maturation of Induced Pluripotent Stem Cell Derived Hepatocytes by
3D-Culture
SO PLOS ONE
LA English
DT Article
ID COLLAGEN-SANDWICH CONFIGURATION; PLASTIC COMPRESSED COLLAGEN;
EXTRACELLULAR-MATRIX; LIVER DEVELOPMENT; LONG-TERM; EXPRESSION; CULTURES
AB Induced pluripotent stem cell derived hepatocytes (IPSC-Heps) have the potential to reduce the demand for a dwindling number of primary cells used in applications ranging from therapeutic cell infusions to in vitro toxicology studies. However, current differentiation protocols and culture methods produce cells with reduced functionality and fetal-like properties compared to adult hepatocytes. We report a culture method for the maturation of IPSC-Heps using 3-Dimensional (3D) collagen matrices compatible with high throughput screening. This culture method significantly increases functional maturation of IPSC-Heps towards an adult phenotype when compared to conventional 2D systems. Additionally, this approach spontaneously results in the presence of polarized structures necessary for drug metabolism and improves functional longevity to over 75 days. Overall, this research reveals a method to shift the phenotype of existing IPSC-Heps towards primary adult hepatocytes allowing such cells to be a more relevant replacement for the current primary standard.
C1 [Gieseck, Richard L., III; Hannan, Nicholas R. F.; Vallier, Ludovic] Univ Cambridge, Wellcome Trust Med Res Council, Stem Cell Inst, Anne McLaren Lab Regenerat Med,Dept Surg, Cambridge, England.
[Gieseck, Richard L., III; Wynn, Thomas A.] NIAID, Immunopathogenesis Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Bort, Roque] Inst Invest Sanitaria La Fe, Unidad Hepatol Expt, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Valencia, Spain.
[Hanley, Neil A.] Univ Manchester, Fac Med & Human Sci, Ctr Endocrinol & Diabet, Inst Human Dev,Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England.
[Drake, Rosemary A. L.; Cameron, Grant W. W.] TAP Biosyst, Royston, England.
[Vallier, Ludovic] Wellcome Trust Sanger Inst, Hinxton, England.
RP Vallier, L (reprint author), Univ Cambridge, Wellcome Trust Med Res Council, Stem Cell Inst, Anne McLaren Lab Regenerat Med,Dept Surg, Cambridge, England.
EM lv225@cam.ac.uk
RI vallier, ludovic/C-6368-2011;
OI Gieseck, Richard/0000-0003-0200-581X; Hanley, Neil/0000-0003-3234-4038;
Bort, Roque/0000-0002-7285-0536; Hannan, Nicholas/0000-0002-9843-1559
FU ERC starting grant; Cambridge Hospitals National Institute for Health
Research Biomedical Research Center; NIH-Oxford Cambridge Scholars
Program Fellowship; Evelyn trust; EU grant InnovaLiv
FX This work was funded by an ERC starting grant (L. V.), the Cambridge
Hospitals National Institute for Health Research Biomedical Research
Center (L. V., N.R.F.H.), the NIH-Oxford Cambridge Scholars Program
Fellowship (R. L. G.), the Evelyn trust (N.R.F.H.), and the EU grant
InnovaLiv (R. L. G, R. B., and L. V.). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 21
TC 41
Z9 42
U1 2
U2 12
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JAN 22
PY 2014
VL 9
IS 1
AR e86372
DI 10.1371/journal.pone.0086372
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 297VL
UT WOS:000330283100149
PM 24466060
ER
PT J
AU Tamim, S
Vo, DT
Uren, PJ
Qiao, M
Bindewald, E
Kasprzak, WK
Shapiro, BA
Nakaya, HI
Burns, SC
Araujo, PR
Nakano, I
Radek, AJ
Kuersten, S
Smith, AD
Penalva, LOF
AF Tamim, Saleh
Vo, Dat T.
Uren, Philip J.
Qiao, Mei
Bindewald, Eckart
Kasprzak, Wojciech K.
Shapiro, Bruce A.
Nakaya, Helder I.
Burns, Suzanne C.
Araujo, Patricia R.
Nakano, Ichiro
Radek, Agnes J.
Kuersten, Scott
Smith, Andrew D.
Penalva, Luiz O. F.
TI Genomic Analyses Reveal Broad Impact of miR-137 on Genes Associated with
Malignant Transformation and Neuronal Differentiation in Glioblastoma
Cells
SO PLOS ONE
LA English
DT Article
ID RNA-BINDING PROTEIN; MICRORNA REPLACEMENT THERAPY; EMBRYONIC STEM-CELLS;
MIB1 LABELING INDEX; DOUBLECORTIN-LIKE; GLIOMA-CELLS; MESSENGER-RNAS;
INTEGRATIVE ANALYSIS; TUMOR-SUPPRESSOR; UBIQUITIN LIGASE
AB miR-137 plays critical roles in the nervous system and tumor development; an increase in its expression is required for neuronal differentiation while its reduction is implicated in gliomagenesis. To evaluate the potential of miR-137 in glioblastoma therapy, we conducted genome-wide target mapping in glioblastoma cells by measuring the level of association between PABP and mRNAs in cells transfected with miR-137 mimics vs. controls via RIPSeq. Impact on mRNA levels was also measured by RNASeq. By combining the results of both experimental approaches, 1468 genes were found to be negatively impacted by miR-137 - among them, 595 (40%) contain miR-137 predicted sites. The most relevant targets include oncogenic proteins and key players in neurogenesis like c-KIT, YBX1, AKT2, CDC42, CDK6 and TGF beta 2. Interestingly, we observed that several identified miR-137 targets are also predicted to be regulated by miR-124, miR-128 and miR-7, which are equally implicated in neuronal differentiation and gliomagenesis. We suggest that the concomitant increase of these four miRNAs in neuronal stem cells or their repression in tumor cells could produce a robust regulatory effect with major consequences to neuronal differentiation and tumorigenesis.
C1 [Tamim, Saleh; Vo, Dat T.; Qiao, Mei; Burns, Suzanne C.; Araujo, Patricia R.; Penalva, Luiz O. F.] Univ Texas Hlth Sci Ctr San Antonio, Childrens Canc Res Inst, San Antonio, TX 78229 USA.
[Uren, Philip J.; Smith, Andrew D.] Univ So Calif, Div Biol Sci, Mol & Computat Biol Sect, Los Angeles, CA USA.
[Bindewald, Eckart; Kasprzak, Wojciech K.] SAIC Frederick Inc, Basic Sci Program, Ctr Canc Res Nanobiol Program, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Shapiro, Bruce A.] NCI, Ctr Canc Res, Nanobiol Program, Frederick, MD 21701 USA.
[Nakaya, Helder I.] Univ Sao Paulo, Inst Pharmaceut Sci, Dept Clin Anal & Toxicol, Sao Paulo, Brazil.
[Nakano, Ichiro] Ohio State Univ, Dept Neurol Surg, James Comprehens Canc Ctr, Columbus, OH 43210 USA.
[Radek, Agnes J.; Kuersten, Scott] Epicentre, Madison, WI USA.
[Penalva, Luiz O. F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA.
RP Penalva, LOF (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Childrens Canc Res Inst, San Antonio, TX 78229 USA.
EM penalva@uthscsa.edu
RI Nakaya, Helder/A-1397-2010; CEPID, CRID/J-2644-2015
OI Nakaya, Helder/0000-0001-5297-9108;
FU National Institutes of Health [HG006015]; IIMS; CTSA (UTHSCSA); Center
for Biomedical Neuroscience (CBN) (UTHSCSA); Max and Minnie Tomerlin
Voelcker Fund; Frederick National Laboratory for Cancer Research,
National Institutes of Health [HHSN261200800001E]; Intramural Research
Program of NIH, Frederick National Laboratory for Cancer Research,
Center for Cancer Research
FX This work was supported by the National Institutes of Health [HG006015
to A.D.S. and L.O.F.P.], IIMS and CTSA (UTHSCSA) [to L.O.F.P.], Center
for Biomedical Neuroscience (CBN) (UTHSCSA) [to L.O.F.P.], and the Max
and Minnie Tomerlin Voelcker Fund [to L.O.F.P.]. This project has been
funded in whole or in part with Federal funds from the Frederick
National Laboratory for Cancer Research, National Institutes of Health,
under contract HHSN261200800001E. The content of this publication does
not necessarily reflect the views or policies of the Department of
Health and Human Services, nor does mention of trade names, commercial
products or organizations imply endorsement by the US Government. This
research was supported [in part] by the Intramural Research Program of
NIH, Frederick National Laboratory for Cancer Research, Center for
Cancer Research. Funding for open access charge: 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 104
TC 11
Z9 11
U1 0
U2 9
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JAN 22
PY 2014
VL 9
IS 1
AR e85591
DI 10.1371/journal.pone.0085591
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 297VL
UT WOS:000330283100048
PM 24465609
ER
PT J
AU Prasad, V
Mailankody, S
AF Prasad, Vinay
Mailankody, Sham
TI The Accelerated Approval of Oncologic Drugs Lessons From Ponatinib
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID CHROMOSOME-POSITIVE LEUKEMIAS
C1 [Prasad, Vinay; Mailankody, Sham] NCI, Med Oncol Serv, Bethesda, MD 20892 USA.
RP Mailankody, S (reprint author), NCI, Med Oncol Serv, NIH, 10 Ctr Dr,10-12N226, Bethesda, MD 20892 USA.
EM sham.mailankody@nih.gov
NR 7
TC 23
Z9 23
U1 0
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JAN 22
PY 2014
VL 311
IS 4
BP 353
EP 354
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 292YT
UT WOS:000329939300015
PM 24449310
ER
PT J
AU Zibly, Z
Levy, I
Litchevski, V
Nass, D
Hofmann, C
Barham, J
Graves, CA
Spiegelmann, R
Hadani, M
Cohen, ZR
AF Zibly, Zion
Levy, Itzchak
Litchevski, Vlady
Nass, Dvora
Hofmann, Chen
Barham, Jacob
Graves, Christian A.
Spiegelmann, Roberto
Hadani, Moshe
Cohen, Zvi R.
TI Brain biopsy in AIDS patients: diagnostic yield and treatment
applications
SO AIDS RESEARCH AND THERAPY
LA English
DT Article
DE HIV; Brain biopsy; CNS AIDS; Neuroimmunology
ID ACTIVE ANTIRETROVIRAL THERAPY; ACQUIRED-IMMUNODEFICIENCY-SYNDROME;
CENTRAL-NERVOUS-SYSTEM; CEREBRAL-LESIONS; STEREOTAXIC BIOPSY; ERA
AB Objective: Central nervous system involvement in AIDS patients can present at any stage of the disease. Brain lesions detected in imaging studies are usually treated empirically. A brain biopsy is indicated in the absence of clinical and radiologic improvement. In the present study, 16 AIDS patients underwent brain biopsy. We evaluated the diagnostic yield of the brain biopsy and the changes in the disease course.
Materials and methods: Sixteen consecutive AIDS patients (12 men, 4 women; mean age 40.8 years) underwent a brain biopsy at Sheba Medical Center between 1997 and 2009. A retrospective analysis was performed and the clinical outcome was recorded.
Results: Median CD4 count before biopsy was 62.6. Magnetic resonance images revealed multiple lesions in 12 patients and enhancing lesions in 12 patients. A total of 19 biopsies were performed in 16 patients. In the present series, the initial procedures provided a diagnostic yield of 81.25% (13 diagnostic cases from 16 procedures in 16 patients). Two of these patients underwent repeated biopsies that were eventually diagnostic. If repeated biopsies were taken into consideration, the diagnostic yield was 93.75% (15 diagnostic cases in 16 patients). The rate of hemorrhagic complications was 10.5% (2 hemorrhages in 19 procedures). Pathologic examination revealed parasitic and fungal infections in 6 patients (6/16; 38%), progressive multifocal leukoencephalopathy in 4 patients (4/16; 25%), AIDS encephalopathy in 4 patients (4/16; 25%), and lymphoma in 1 patient (1/16; 6%). One patient had a nonspecific inflammatory process (6%). The treatment modality was modified in 12 patients and led to clinical and radiologic improvement in 8 patients.
Conclusions: Brain biopsy should be considered when empiric treatment of central nervous system lesions in AIDS patients fails. Biopsy is diagnostic in the majority of patients. The diagnosis allows for treatment modifications, which lead to clinical and radiologic improvement in some patients.
C1 [Spiegelmann, Roberto; Hadani, Moshe; Cohen, Zvi R.] Sheba Med Ctr, Dept Neurosurg, Ramat Gan, Israel.
[Nass, Dvora] Sheba Med Ctr, Inst Pathol, Ramat Gan, Israel.
[Levy, Itzchak; Litchevski, Vlady] Sheba Med Ctr, AIDS Ctr, Ramat Gan, Israel.
[Hofmann, Chen] Sheba Med Ctr, Inst Radiol, Ramat Gan, Israel.
[Barham, Jacob] Sheba Med Ctr, Ctr Oncol, Ramat Gan, Israel.
[Graves, Christian A.] Univ S Carolina, Sch Med, Dept Pathol Microbiol & Immunol, Columbia, SC USA.
[Zibly, Zion] NINDS, NIH, Bethesda, MD 20892 USA.
RP Cohen, ZR (reprint author), Sheba Med Ctr, Dept Neurosurg, Ramat Gan, Israel.
EM Zvi.Cohen@sheba.health.gov.il
NR 29
TC 4
Z9 4
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-6405
J9 AIDS RES THER
JI Aids Res. Ther.
PD JAN 21
PY 2014
VL 11
AR 4
DI 10.1186/1742-6405-11-4
PG 5
WC Infectious Diseases
SC Infectious Diseases
GA AB8FX
UT WOS:000332026700001
PM 24447375
ER
PT J
AU Shin, HW
Ocola, EJ
Kim, S
Laane, J
AF Shin, Hee Won
Ocola, Esther J.
Kim, Sunghwan
Laane, Jaan
TI Fluorescence excitation and ultraviolet absorption spectra and
theoretical calculations for benzocyclobutane: Vibrations and structure
of its excited S-1(pi,pi*) electronic state
SO JOURNAL OF CHEMICAL PHYSICS
LA English
DT Article
ID LASER-INDUCED FLUORESCENCE; AB-INITIO CALCULATIONS; 1,4-BENZODIOXAN;
RAMAN; SPECTROSCOPY; S-0
AB The fluorescence excitation spectra of jet-cooled benzocyclobutane have been recorded and together with its ultraviolet absorption spectra have been used to assign the vibrational frequencies for this molecule in its S-1(pi,pi*) electronic excited state. Theoretical calculations at the CASSCF(6,6)/aug-cc- pVTZ level of theory were carried out to compute the structure of the molecule in its excited state. The calculated structure was compared to that of the molecule in its electronic ground state as well as to the structures of related molecules in their S-0 and S-1(pi,pi*) electronic states. In each case the decreased pi bonding in the electronic excited states results in longer carbon-carbon bonds in the benzene ring. The skeletal vibrational frequencies in the electronic excited state were readily assigned and these were compared to the ground state and to the frequencies of five similarmolecules. The vibrational levels in both S-0 and S-1(pi,pi*) states were remarkably harmonic in contrast to the other bicyclic molecules. The decreases in the frequencies of the out-of-plane skeletal modes reflect the increased floppiness of these bicyclic molecules in their S-1(pi,pi*) excited state. (C) 2014 AIP Publishing LLC.
C1 [Shin, Hee Won; Ocola, Esther J.; Laane, Jaan] Texas A&M Univ, Dept Chem, College Stn, TX 77843 USA.
[Kim, Sunghwan] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Dept Hlth & Human Serv, Bethesda, MD 20894 USA.
RP Laane, J (reprint author), Texas A&M Univ, Dept Chem, College Stn, TX 77843 USA.
EM laane@mail.chem.tamu.edu
RI Kim, Sunghwan/A-6738-2008; Laane, Jaan/O-4379-2014
OI Kim, Sunghwan/0000-0001-9828-2074; Laane, Jaan/0000-0003-4423-6122
FU Robert A. Welch Foundation [A-0396]; Intramural Research Program of the
National Institutes of Health (NIH); National Library of Medicine (NLM);
National Science Foundation [CHE-0541587]
FX J.L. wishes to thank the Robert A. Welch Foundation (Grant No. A-0396)
for financial support. S. K. received funding from the Intramural
Research Program of the National Institutes of Health (NIH), National
Library of Medicine (NLM). Computations by J.L. and E.J.O. were carried
out on the Texas A&M University Department of Chemistry Medusa computer
system funded by the National Science Foundation, Grant No. CHE-0541587
and S. K. utilized the Biowulf Linux cluster at the NIH, Bethesda, MD
(http://biowulf.nih.gov). The Laboratory for Molecular Simulation
provided the Semichem AMPAC/AGUI software used by J.L. and E.J.O.
NR 26
TC 0
Z9 0
U1 0
U2 7
PU AMER INST PHYSICS
PI MELVILLE
PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1,
MELVILLE, NY 11747-4501 USA
SN 0021-9606
EI 1089-7690
J9 J CHEM PHYS
JI J. Chem. Phys.
PD JAN 21
PY 2014
VL 140
IS 3
AR 034305
DI 10.1063/1.4858412
PG 10
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 302OM
UT WOS:000330614400023
PM 25669377
ER
PT J
AU Albanese, E
Strand, BH
Guralnik, JM
Patel, KV
Kuh, D
Hardy, R
AF Albanese, Emiliano
Strand, Bjorn Heine
Guralnik, Jack M.
Patel, Kushang V.
Kuh, Diana
Hardy, Rebecca
TI Weight Loss and Premature Death: The 1946 British Birth Cohort Study
SO PLOS ONE
LA English
DT Article
ID BODY-MASS INDEX; ALL-CAUSE MORTALITY; OLD-AGE; CARDIOVASCULAR HEALTH;
LIFE-COURSE; MIDDLE-AGE; RISK; MEN; ASSOCIATION; DISEASE
AB Objective: The relationship between weight loss and mortality has important clinical and public health significance but has proved to be complex. Evidence is mixed and particularly limited on the association between weight loss in mid-life and premature death (i.e. before 65 years of age), a small albeit important segment of total mortality. We aimed to study the association between midlife weight change and mortality accounting for health and lifestyle characteristics, and also considering potential bias due to preexisting chronic diseases and smoking status.
Design: Longitudinal, population-based, 'the 1946 British' birth cohort study.
Subjects and Measures: In 2750 men and women, mortality from age 53 through 65 years was analyzed according to categories of measured 10 year weight change between 43 and 53 years. Cox's hazard ratios (HR) were progressively adjusted for socio-demographic, lifestyle and health characteristics.
Results: Nearly 20% of participants lost weight and over 50% gained 5 kg or more in midlife. There were 164 deaths. Compared to those who gained between 2 and 5 kg, those who lost 5 kg or more had an increased risk of premature death independently of midlife physical activity, socio-economic circumstances and educational attainment. This association was unaltered when highest weight loss (lost more than 15 Kg) (p = 0.04) and early deaths were excluded (p<0.001), but was no longer significant after adjustment for cardiovascular risk factors and health status (HR = 1.8; 95% CI: 0.9 to 3.5).
Conclusion: The inverse association between weight loss in midlife and higher risk of premature death may be explained by vascular risk factors and ill health. In consideration of the burden of premature death, closer monitoring of weight loss in mid-life is warranted.
C1 [Albanese, Emiliano] NIA, Lab Populat Sci, Bethesda, MD 20892 USA.
[Strand, Bjorn Heine] Norwegian Inst Publ Hlth, Oslo, Norway.
[Guralnik, Jack M.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Patel, Kushang V.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA.
[Kuh, Diana; Hardy, Rebecca] UCL, MRC Unit Lifelong Hlth & Ageing, London, England.
RP Albanese, E (reprint author), NIA, Lab Populat Sci, Bethesda, MD 20892 USA.
EM emiliano.albanese@gmail.com
OI Strand, Bjorn/0000-0003-4385-8886
FU MRC Unit for Lifelong Health and Ageing, UK; National Institute on
Aging, National Institutes of Health
FX The NSHD study is funded by the MRC Unit for Lifelong Health and Ageing,
UK and was supported in part by the Intramural Research Program of the
National Institute on Aging, 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 35
TC 1
Z9 1
U1 1
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JAN 21
PY 2014
VL 9
IS 1
AR e86282
DI 10.1371/journal.pone.0086282
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 297GT
UT WOS:000330244500216
PM 24466002
ER
PT J
AU Boularan, C
Kamenyeva, O
Cho, H
Kehrl, JH
AF Boularan, Cedric
Kamenyeva, Olena
Cho, Hyeseon
Kehrl, John H.
TI Resistance to Inhibitors of Cholinesterase (Ric)-8A and G alpha(i)
Contribute to Cytokinesis Abscission by Controlling Vacuolar
Protein-Sorting (Vps)34 Activity
SO PLOS ONE
LA English
DT Article
ID PHOSPHORYLATION-DEPENDENT UBIQUITINATION; HETEROTRIMERIC G-PROTEINS;
CELL-DIVISION; ASYMMETRIC DIVISION; ALPHA-SUBUNIT; LOCALIZATION; RIC-8;
MIDBODY; SPINDLE; MODULATION
AB Resistance to inhibitors of cholinesterase (Ric)-8A is a guanine nucleotide exchange factor for G alpha(i), G alpha(q), and G alpha(12/13), which is implicated in cell signaling and as a molecular chaperone required for the initial association of nascent G alpha subunits with cellular membranes. Ric-8A, G alpha(i) subunits, and their regulators are localized at the midbody prior to abscission and linked to the final stages of cell division. Here, we identify a molecular mechanism by which Ric-8A affects cytokinesis and abscission by controlling Vps34 activity. We showed that Ric-8A protein expression is post-transcriptionally controlled during the cell cycle reaching its maximum levels at mitosis. A FRET biosensor created to measure conformational changes in Ric-8A by FLIM (Fluorescence Lifetime Imaging Microscopy) revealed that Ric-8A was in a close-state during mitosis and particularly so at cytokinesis. Lowering Ric-8A expression delayed the abscission time of dividing cells, which correlated with increased intercellular bridge length and multinucleation. During cytokinesis, Ric-8A co-localized with Vps34 at the midbody along with G alpha(i) and LGN, where these proteins functioned to regulate Vps34 phosphatidylinositol 3-kinase activity.
C1 [Boularan, Cedric; Kamenyeva, Olena; Cho, Hyeseon; Kehrl, John H.] NIAID, Cell Mol Immunol Sect B, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
RP Kehrl, JH (reprint author), NIAID, Cell Mol Immunol Sect B, Immunoregulat Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM jkehrl@niaid.nih.gov
FU 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 47
TC 7
Z9 7
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JAN 21
PY 2014
VL 9
IS 1
AR e86680
DI 10.1371/journal.pone.0086680
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 297GT
UT WOS:000330244500271
PM 24466196
ER
PT J
AU Farnan, L
Ivanova, A
Peddada, SD
AF Farnan, Laura
Ivanova, Anastasia
Peddada, Shyamal D.
TI Linear Mixed Effects Models under Inequality Constraints with
Applications
SO PLOS ONE
LA English
DT Article
ID ORDER-RESTRICTED INFERENCE; ZERO DOSE CONTROL; CELL-CYCLE;
GENE-EXPRESSION; LONGITUDINAL DATA; FISSION YEAST; HEARING-LOSS; BRAIN;
RATES; TIME
AB Constraints arise naturally in many scientific experiments/studies such as in, epidemiology, biology, toxicology, etc. and often researchers ignore such information when analyzing their data and use standard methods such as the analysis of variance (ANOVA). Such methods may not only result in a loss of power and efficiency in costs of experimentation but also may result poor interpretation of the data. In this paper we discuss constrained statistical inference in the context of linear mixed effects models that arise naturally in many applications, such as in repeated measurements designs, familial studies and others. We introduce a novel methodology that is broadly applicable for a variety of constraints on the parameters. Since in many applications sample sizes are small and/or the data are not necessarily normally distributed and furthermore error variances need not be homoscedastic (i.e. heterogeneity in the data) we use an empirical best linear unbiased predictor (EBLUP) type residual based bootstrap methodology for deriving critical values of the proposed test. Our simulation studies suggest that the proposed procedure maintains the desired nominal Type I error while competing well with other tests in terms of power. We illustrate the proposed methodology by re-analyzing a clinical trial data on blood mercury level. The methodology introduced in this paper can be easily extended to other settings such as nonlinear and generalized regression models.
C1 [Farnan, Laura] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Ivanova, Anastasia] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA.
[Peddada, Shyamal D.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA.
RP Peddada, SD (reprint author), NIEHS, Biostat Branch, POB 12233, Res Triangle Pk, NC 27709 USA.
EM peddada@niehs.nih.gov
FU NIEHS, National Institutes of Health [Z01 ES102345-04]; National
Institutes of Health [RO1 CA120082-01A1]
FX The research of SDP was supported by the Intramural Research Program of
the NIEHS, National Institutes of Health (Z01 ES102345-04). LF and AI
work was supported in part by National Institutes of Health grant RO1
CA120082-01A1. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 30
TC 2
Z9 2
U1 0
U2 12
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JAN 21
PY 2014
VL 9
IS 1
AR e84778
DI 10.1371/journal.pone.0084778
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 297GT
UT WOS:000330244500015
PM 24465432
ER
PT J
AU Smith, S
Tripathi, R
Goodings, C
Cleveland, S
Mathias, E
Hardaway, JA
Elliott, N
Yi, YJ
Chen, X
Downing, J
Mullighan, C
Swing, DA
Tessarollo, L
Li, LQ
Love, P
Jenkins, NA
Copeland, NG
Thompson, MA
Du, Y
Dave, UP
AF Smith, Stephen
Tripathi, Rati
Goodings, Charnise
Cleveland, Susan
Mathias, Elizabeth
Hardaway, J. Andrew
Elliott, Natalina
Yi, Yajun
Chen, Xi
Downing, James
Mullighan, Charles
Swing, Deborah A.
Tessarollo, Lino
Li, Liqi
Love, Paul
Jenkins, Nancy A.
Copeland, Neal G.
Thompson, Mary Ann
Du, Yang
Dave, Utpal P.
TI LIM Domain Only-2 (LMO2) Induces T-Cell Leukemia by Two Distinct
Pathways
SO PLOS ONE
LA English
DT Article
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; GENOME-WIDE ANALYSIS; HOMEOBOX GENE HEX;
LIM-PROTEIN LMO2; TRANSCRIPTION FACTOR; RETROVIRAL INSERTION;
HEMATOPOIETIC STEM; ONLY PROTEINS; MOUSE MODEL; FORMS PART
AB The LMO2 oncogene is deregulated in the majority of human T-cell leukemia cases and in most gene therapy-induced T-cell leukemias. We made transgenic mice with enforced expression of Lmo2 in T-cells by the CD2 promoter/enhancer. These transgenic mice developed highly penetrant T-ALL by two distinct patterns of gene expression: one in which there was concordant activation of Lyl1, Hhex, and Mycn or alternatively, with Notch1 target gene activation. Most strikingly, this gene expression clustering was conserved in human Early T-cell Precursor ALL (ETP-ALL), where LMO2, HHEX, LYL1, and MYCN were most highly expressed. We discovered that HHEX is a direct transcriptional target of LMO2 consistent with its concordant gene expression. Furthermore, conditional inactivation of Hhex in CD2-Lmo2 transgenic mice markedly attenuated T-ALL development, demonstrating that Hhex is a crucial mediator of Lmo2's oncogenic function. The CD2-Lmo2 transgenic mice offer mechanistic insight into concordant oncogene expression and provide a model for the highly treatment-resistant ETP-ALL subtype.
C1 [Smith, Stephen; Tripathi, Rati; Goodings, Charnise; Cleveland, Susan; Mathias, Elizabeth; Elliott, Natalina; Dave, Utpal P.] Vanderbilt Univ, Med Ctr, Div Hematol Oncol, Nashville, TN 37212 USA.
[Smith, Stephen; Tripathi, Rati; Goodings, Charnise; Cleveland, Susan; Mathias, Elizabeth; Elliott, Natalina; Dave, Utpal P.] Tennessee Valley Healthcare Syst, Nashville, TN USA.
[Hardaway, J. Andrew] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA.
[Yi, Yajun] Vanderbilt Univ, Med Ctr, Div Med Genet, Nashville, TN USA.
[Chen, Xi] Vanderbilt Univ, Med Ctr, Dept Biostat, Nashville, TN USA.
[Downing, James; Mullighan, Charles] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA.
[Swing, Deborah A.; Tessarollo, Lino] NCI, Mouse Canc Genet Program, Frederick, MD 21701 USA.
[Li, Liqi; Love, Paul] NICHHD, NIH, Bethesda, MD 20892 USA.
[Jenkins, Nancy A.; Copeland, Neal G.] Methodist Hosp, Res Inst, Houston, TX 77030 USA.
[Thompson, Mary Ann] Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA.
[Du, Yang] Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD 20814 USA.
RP Dave, UP (reprint author), Vanderbilt Univ, Med Ctr, Div Hematol Oncol, Nashville, TN 37212 USA.
EM utpal.dave@vanderbilt.edu
OI Mullighan, Charles/0000-0002-1871-1850
FU Department of Veterans Affairs, Veterans Health Administration, Office
of Research and Development, Biomedical Laboratory Research and
Development [BX001799-01A1]; National Institutes of Health (NIH)
[K08HL089403]; Leukemia & Lymphoma Society; Vanderbilt Ingram Cancer
Center [P30 CA68485]; Vanderbilt Digestive Disease Research Center
[DK058404]; Cancer Prevention Research Institute of Texas (CPRIT);
American Society of Hematology
FX This work was supported by a VA Merit award, BX001799-01A1 (UPD), by the
Department of Veterans Affairs, Veterans Health Administration, Office
of Research and Development, Biomedical Laboratory Research and
Development and the National Institutes of Health (NIH) grant
K08HL089403, the Leukemia & Lymphoma Society, and the Vanderbilt Ingram
Cancer Center (P30 CA68485) (UPD). The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Cancer Institute or the NIH. The VMC Flow
Cytometry Shared Resource is supported by the Vanderbilt Ingram Cancer
Center (P30 CA68485) and the Vanderbilt Digestive Disease Research
Center (DK058404). NGC and NAJ are supported in part by the Cancer
Prevention Research Institute of Texas (CPRIT). They are also both CPRIT
Scholars in Cancer Research. This work was also supported by a Bridge
Grant from the American Society of Hematology. The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 57
TC 19
Z9 19
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 JAN 21
PY 2014
VL 9
IS 1
AR e85883
DI 10.1371/journal.pone.0085883
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 297GT
UT WOS:000330244500135
PM 24465765
ER
PT J
AU Steidl, S
Wang, HL
Wise, RA
AF Steidl, Stephan
Wang, Huiling
Wise, Roy A.
TI Lesions of Cholinergic Pedunculopontine Tegmental Nucleus Neurons Fail
to Affect Cocaine or Heroin Self-Administration or Conditioned Place
Preference in Rats
SO PLOS ONE
LA English
DT Article
ID REWARDING BRAIN-STIMULATION; DOPAMINE NEURONS; MESOPONTINE TEGMENTUM;
ACETYLCHOLINE-RELEASE; MUSCARINIC RECEPTORS; GLUTAMATE RECEPTORS; AREA;
REINFORCEMENT; INVOLVEMENT; ACTIVATION
AB Cholinergic input to the ventral tegmental area (VTA) is known to contribute to reward. Although it is known that the pedunculopontine tegmental nucleus (PPTg) provides an important source of excitatory input to the dopamine system, the specific role of PPTg cholinergic input to the VTA in cocaine reward has not been previously determined. We used a diphtheria toxin conjugated to urotensin-II (Dtx::UII), the endogenous ligand for urotensin-II receptors expressed by PPTg cholinergic but not glutamatergic or GABAergic cells, to lesion cholinergic PPTg neurons. Dtx::UII toxin infusion resulted in the loss of 95.78 (+/- 0.65)% of PPTg cholinergic cells but did not significantly alter either cocaine or heroin self-administration or the development of cocaine or heroin conditioned place preferences. Thus, cholinergic cells originating in PPTg do not appear to be critical for the rewarding effects of cocaine or of heroin.
C1 [Steidl, Stephan; Wang, Huiling; Wise, Roy A.] NIDA, Intramural Res Program, NIH, US Dept HHS, Baltimore, MD USA.
RP Steidl, S (reprint author), Loyola Univ, Dept Psychol, 6525 N Sheridan Rd, Chicago, IL 60626 USA.
EM ssteidl@luc.edu
FU National Institute on Drug Abuse, National Institutes of Health,
Department of Health and Human Services
FX Funding was provided by the Intramural Research Program, National
Institute on Drug Abuse, National Institutes of Health, Department of
Health and Human Services. The funders had no role in the study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 28
TC 10
Z9 10
U1 1
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JAN 21
PY 2014
VL 9
IS 1
AR e84412
DI 10.1371/journal.pone.0084412
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 297GT
UT WOS:000330244500004
PM 24465410
ER
PT J
AU Westmoreland, SV
Converse, AP
Hrecka, K
Hurley, M
Knight, H
Piatak, M
Lifson, J
Mansfield, KG
Skowronski, J
Desrosiers, RC
AF Westmoreland, Susan V.
Converse, A. Peter
Hrecka, Kasia
Hurley, Mollie
Knight, Heather
Piatak, Michael
Lifson, Jeffrey
Mansfield, Keith G.
Skowronski, Jacek
Desrosiers, Ronald C.
TI SIV Vpx Is Essential for Macrophage Infection but Not for Development of
AIDS
SO PLOS ONE
LA English
DT Article
ID SIMIAN-IMMUNODEFICIENCY-VIRUS; CD4(+) T-CELLS; COLONY-STIMULATING
FACTOR; SAMHD1 RESTRICTS; RHESUS-MONKEYS; HIV-1 INFECTION; PRIMATE
LENTIVIRUSES; DISEASE PROGRESSION; VACCINE PROTECTION; IMMUNE-RESPONSES
AB Analysis of rhesus macaques infected with a vpx deletion mutant virus of simian immunodeficiency virus mac239 (SIV Delta vpx) demonstrates that Vpx is essential for efficient monocyte/macrophage infection in vivo but is not necessary for development of AIDS. To compare myeloid-lineage cell infection in monkeys infected with SIV Delta vpx compared to SIVmac239, we analyzed lymphoid and gastrointestinal tissues from SIV Delta vpx-infected rhesus (n = 5), SIVmac239-infected rhesus with SIV encephalitis (7 SIV239E), those without encephalitis (4 SIV239noE), and other SIV mutant viruses with low viral loads (4 SIV Delta nef, 2 SIV Delta 3). SIV+ macrophages and the percentage of total SIV+ cells that were macrophages in spleen and lymph nodes were significantly lower in rhesus infected with SIV Delta vpx (2.2%) compared to those infected with SIV239E (22.7%), SIV239noE (8.2%), and SIV mutant viruses (10.1%). In colon, SIV Delta vpx monkeys had fewer SIV+ cells, no SIV+ macrophages, and lower percentage of SIV+ cells that were macrophages than the other 3 groups. Only 2 SIV Delta vpx monkeys exhibited detectable virus in the colon. We demonstrate that Vpx is essential for efficient macrophage infection in vivo and that simian AIDS and death can occur in the absence of detectable macrophage infection.
C1 [Westmoreland, Susan V.; Converse, A. Peter; Hurley, Mollie; Knight, Heather; Mansfield, Keith G.] Harvard Univ, Sch Med, New England Primate Res Ctr, Div Comparat Pathol, Southborough, MA 01772 USA.
[Piatak, Michael; Lifson, Jeffrey] NCI, AIDS & Canc Virus Program, SAIC Frederick, Frederick, MD 21701 USA.
[Hrecka, Kasia; Skowronski, Jacek] Case Western Reserve Univ, Sch Med, Dept Mol Biol & Microbiol, Cleveland, OH 44106 USA.
[Desrosiers, Ronald C.] Harvard Univ, Sch Med, New England Primate Res Ctr, Div Microbiol, Southborough, MA 01772 USA.
RP Westmoreland, SV (reprint author), Harvard Univ, Sch Med, New England Primate Res Ctr, Div Comparat Pathol, Southborough, MA 01772 USA.
EM susan_westmoreland@hms.harvard.edu
FU NIH [P51 1OD011103, 5 R01 AI25328-22, R01 AI077459, T32 OD011064];
National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX NIH grants P51 1OD011103, 5 R01 AI25328-22, R01 AI077459, T32 OD011064,
National Cancer Institute, National Institutes of Health under contract
No. HHSN261200800001E. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 51
TC 11
Z9 11
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JAN 21
PY 2014
VL 9
IS 1
AR e84463
DI 10.1371/journal.pone.0084463
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 297GT
UT WOS:000330244500005
PM 24465411
ER
PT J
AU Berezhkovskii, AM
Dagdug, L
Bezrukov, SM
AF Berezhkovskii, Alexander M.
Dagdug, Leonardo
Bezrukov, Sergey M.
TI Discriminating between Anomalous Diffusion and Transient Behavior in
Microheterogeneous Environments
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID SPINES
AB Diffusion in macrohomogeneous and microheterogeneous media can be described as effective free diffusion only at sufficiently long times. At intermediate times, the mean-square displacement of a diffusing object shows a transient behavior that can be misinterpreted as anomalous subdiffusion. We discuss how to discriminate between the two.
C1 [Berezhkovskii, Alexander M.; Bezrukov, Sergey M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD USA.
[Berezhkovskii, Alexander M.; Dagdug, Leonardo] NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
[Dagdug, Leonardo] Univ Autonoma Metropolitana Iztapalapa, Dept Fis, Iztapalapa, Mexico.
RP Bezrukov, SM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD USA.
EM bezrukos@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health, Center
for Information Technology; Consejo Nacional de Ciencia y Tecnologia
[176452]; Eunice Kennedy Shriver National Institute of Child Health and
Human Development
FX This study was supported by the Intramural Research Program of the
National Institutes of Health, Center for Information Technology and
Eunice Kennedy Shriver National Institute of Child Health and Human
Development. L.D. thanks Consejo Nacional de Ciencia y Tecnologia for
partial support under grant No. 176452.
NR 11
TC 19
Z9 19
U1 1
U2 9
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 21
PY 2014
VL 106
IS 2
BP L09
EP L11
DI 10.1016/j.bpj.2013.12.013
PG 3
WC Biophysics
SC Biophysics
GA 295RF
UT WOS:000330132500002
PM 24461027
ER
PT J
AU Go, AS
Mozaffarian, D
Roger, VL
Benjamin, EJ
Berry, JD
Blaha, MJ
Dai, SF
Ford, ES
Fox, CS
Franco, S
Fullerton, HJ
Gillespie, C
Hailpern, SM
Heit, JA
Howard, VJ
Huffman, MD
Judd, SE
Kissela, BM
Kittner, SJ
Lackland, DT
Lichtman, JH
Lisabeth, LD
Mackey, RH
Magid, DJ
Marcus, GM
Marelli, A
Matchar, DB
McGuire, DK
Mohler, ER
Moy, CS
Mussolino, ME
Neumar, RW
Nichol, G
Pandey, DK
Paynter, NP
Reeves, MJ
Sorlie, PD
Stein, J
Towfighi, A
Turan, TN
Virani, SS
Wong, ND
Woo, D
Turner, MB
AF Go, Alan S.
Mozaffarian, Dariush
Roger, Veronique L.
Benjamin, Emelia J.
Berry, Jarett D.
Blaha, Michael J.
Dai, Shifan
Ford, Earl S.
Fox, Caroline S.
Franco, Sheila
Fullerton, Heather J.
Gillespie, Cathleen
Hailpern, Susan M.
Heit, John A.
Howard, Virginia J.
Huffman, Mark D.
Judd, Suzanne E.
Kissela, Brett M.
Kittner, Steven J.
Lackland, Daniel T.
Lichtman, Judith H.
Lisabeth, Lynda D.
Mackey, Rachel H.
Magid, David J.
Marcus, Gregory M.
Marelli, Ariane
Matchar, David B.
McGuire, Darren K.
Mohler, Emile R., III
Moy, Claudia S.
Mussolino, Michael E.
Neumar, Robert W.
Nichol, Graham
Pandey, Dilip K.
Paynter, Nina P.
Reeves, Matthew J.
Sorlie, Paul D.
Stein, Joel
Towfighi, Amytis
Turan, Tanya N.
Virani, Salim S.
Wong, Nathan D.
Woo, Daniel
Turner, Melanie B.
CA Amer Heart Assoc Stroke Stat
Stroke Statistics Subcomm
TI Executive Summary: Heart Disease and Stroke Statistics-2014 Update A
Report From the American Heart Association
SO CIRCULATION
LA English
DT Article
DE AHA Scientific Statements; cardiovascular diseases; epidemiology; risk
factors; statistics; stroke
C1 [Go, Alan S.] Kaiser Permanente, Oakland, CA 94612 USA.
[Mozaffarian, Dariush] Harvard Univ, Sch Med, Brigham & Womens Hosp, Cambridge, MA 02138 USA.
[Mozaffarian, Dariush] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA.
[Roger, Veronique L.; Heit, John A.] Mayo Clin, Rochester, MN USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Boston, MA 02215 USA.
[Berry, Jarett D.] UT Southwestern, Dallas, TX USA.
[Blaha, Michael J.] Johns Hopkins, Baltimore, MD USA.
[Dai, Shifan; Ford, Earl S.; Gillespie, Cathleen] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Fox, Caroline S.; Mussolino, Michael E.] NHLBI, Bethesda, MD USA.
[Franco, Sheila] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Atlanta, GA USA.
[Fullerton, Heather J.; Marcus, Gregory M.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Howard, Virginia J.; Judd, Suzanne E.] Univ Alabama Birmingham, Birmingham, AL USA.
[Huffman, Mark D.] Northwestern Univ, Feinberg Sch Med, Evanston, IL 60208 USA.
[Kissela, Brett M.; Woo, Daniel] Univ Cincinnati, Cincinnati, OH 45221 USA.
[Kittner, Steven J.] Univ Maryland, Sch Med, College Pk, MD 20742 USA.
[Kittner, Steven J.] Vet Adm Hlth Care Syst, Washington, DC USA.
[Lackland, Daniel T.; Turan, Tanya N.] Med Univ S Carolina, Charleston, SC USA.
[Lichtman, Judith H.] Yale Univ, New Haven, CT 06520 USA.
[Lisabeth, Lynda D.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Mackey, Rachel H.] Univ Pittsburgh, Pittsburgh, PA 15260 USA.
[Magid, David J.] Colorado Permanente Med Grp, Denver, CO USA.
[Marelli, Ariane] McGill Univ, Ctr Hlth, Montreal, PQ H3A 2T5, Canada.
[Matchar, David B.] Duke Univ, Med Ctr, Duke NUS Grad Med Sch, Durham, NC 27706 USA.
[McGuire, Darren K.] UT South western Med Ctr, Dallas, TX USA.
[Mohler, Emile R., III] Univ Penn, Philadelphia, PA 19104 USA.
[Moy, Claudia S.] NIH, Bethesda, MD USA.
[Neumar, Robert W.] Univ Michigan Hlth Syst, Ann Arbor, MI USA.
[Nichol, Graham] Univ Washington, Seattle, WA 98195 USA.
[Pandey, Dilip K.] Univ Illinois, Chicago, IL USA.
[Paynter, Nina P.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Reeves, Matthew J.] Michigan State Univ, E Lansing, MI 48824 USA.
[Sorlie, Paul D.] NHLBI, NIH, Bethesda, MD USA.
[Stein, Joel] Columbia Univ, New York, NY 10027 USA.
[Towfighi, Amytis] Univ So Calif, Los Angeles, CA 90089 USA.
[Turner, Melanie B.] Amer Heart Assoc, Dallas, TX USA.
[Virani, Salim S.] Baylor Coll Med, Dept Vet Affairs, Houston, TX 77030 USA.
[Wong, Nathan D.] Univ Calif Irvine, Irvine, CA 92717 USA.
RP Go, AS (reprint author), Kaiser Permanente, Oakland, CA 94612 USA.
OI Mackey, Rachel/0000-0001-6088-2664; Matchar, David/0000-0003-3020-2108;
Turan, Tanya/0000-0001-5399-8845; Huffman, Mark/0000-0001-7412-2519;
Benjamin, Emelia/0000-0003-4076-2336; Virani, Salim/0000-0001-9541-6954;
Kissela, Brett/0000-0002-9773-4013
FU NCATS NIH HHS [UL1 TR001425]
NR 2
TC 489
Z9 514
U1 6
U2 109
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 JAN 21
PY 2014
VL 129
IS 3
BP 399
EP 410
DI 10.1161/01.cir.0000442015.53336.12
PG 12
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 292CV
UT WOS:000329880700020
PM 24446411
ER
PT J
AU Go, AS
Mozaffarian, D
Roger, VL
Benjamin, EJ
Berry, JD
Blaha, MJ
Dai, SF
Ford, ES
Fox, CS
Franco, S
Fullerton, HJ
Gillespie, C
Hailpern, SM
Heit, JA
Howard, VJ
Huffman, MD
Judd, SE
Kissela, BM
Kittner, SJ
Lackland, DT
Lichtman, JH
Lisabeth, LD
Mackey, RH
Magid, DJ
Marcus, GM
Marelli, A
Matchar, DB
McGuire, DK
Mohler, ER
Moy, CS
Mussolino, ME
Neumar, RW
Nichol, G
Pandey, DK
Paynter, NP
Reeves, MJ
Sorlie, PD
Stein, J
Towfighi, A
Turan, TN
Virani, SS
Wong, ND
Woo, D
Turner, MB
AF Go, Alan S.
Mozaffarian, Dariush
Roger, Veronique L.
Benjamin, Emelia J.
Berry, Jarett D.
Blaha, Michael J.
Dai, Shifan
Ford, Earl S.
Fox, Caroline S.
Franco, Sheila
Fullerton, Heather J.
Gillespie, Cathleen
Hailpern, Susan M.
Heit, John A.
Howard, Virginia J.
Huffman, Mark D.
Judd, Suzanne E.
Kissela, Brett M.
Kittner, Steven J.
Lackland, Daniel T.
Lichtman, Judith H.
Lisabeth, Lynda D.
Mackey, Rachel H.
Magid, David J.
Marcus, Gregory M.
Marelli, Ariane
Matchar, David B.
McGuire, Darren K.
Mohler, Emile R., III
Moy, Claudia S.
Mussolino, Michael E.
Neumar, Robert W.
Nichol, Graham
Pandey, Dilip K.
Paynter, Nina P.
Reeves, Matthew J.
Sorlie, Paul D.
Stein, Joel
Towfighi, Amytis
Turan, Tanya N.
Virani, Salim S.
Wong, Nathan D.
Woo, Daniel
Turner, Melanie B.
CA Amer Heart Assoc Stat Comm
Stroke Stat Subcomm
TI Heart Disease and Stroke Statistics-2014 Update A Report From the
American Heart Association
SO CIRCULATION
LA English
DT Article
DE AHA Scientific Statements; cardiovascular diseases; epidemiology; risk
factors; statistics; stroke
C1 [Go, Alan S.] Kaiser Permanente, Oakland, CA 94612 USA.
[Mozaffarian, Dariush] Harvard Univ, Sch Med, Brigham & Womens Hosp, Cambridge, MA 02138 USA.
[Mozaffarian, Dariush] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA.
[Roger, Veronique L.; Heit, John A.] Mayo Clin, Rochester, MN USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Boston, MA 02215 USA.
[Berry, Jarett D.] UT Southwestern, Dallas, TX USA.
[Blaha, Michael J.] Johns Hopkins, Baltimore, MD USA.
[Dai, Shifan; Ford, Earl S.; Gillespie, Cathleen] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Fox, Caroline S.; Mussolino, Michael E.] NHLBI, Bethesda, MD USA.
[Franco, Sheila] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Atlanta, GA USA.
[Fullerton, Heather J.; Marcus, Gregory M.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Howard, Virginia J.; Judd, Suzanne E.] Univ Alabama Birmingham, Birmingham, AL USA.
[Huffman, Mark D.] Northwestern Univ, Feinberg Sch Med, Evanston, IL 60208 USA.
[Kissela, Brett M.; Woo, Daniel] Univ Cincinnati, Cincinnati, OH 45221 USA.
[Kittner, Steven J.] Univ Maryland, Sch Med, College Pk, MD 20742 USA.
[Kittner, Steven J.] Vet Adm Hlth Care Syst, Washington, DC USA.
[Lackland, Daniel T.; Turan, Tanya N.] Med Univ S Carolina, Charleston, SC USA.
[Lichtman, Judith H.] Yale Univ, New Haven, CT 06520 USA.
[Lisabeth, Lynda D.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Mackey, Rachel H.] Univ Pittsburgh, Pittsburgh, PA 15260 USA.
[Magid, David J.] Colorado Permanente Med Grp, Denver, CO USA.
[Marelli, Ariane] McGill Univ, Ctr Hlth, Montreal, PQ H3A 2T5, Canada.
[Matchar, David B.] Duke Univ, Ctr Med, Duke NUS Grad Med Sch, Durham, NC 27706 USA.
[McGuire, Darren K.] UT South Western Med Ctr, Dallas, TX USA.
[Mohler, Emile R., III] Univ Penn, Philadelphia, PA 19104 USA.
[Moy, Claudia S.] NIH, Bethesda, MD USA.
[Neumar, Robert W.] Univ Michigan Hlth Syst, Ann Arbor, MI USA.
[Nichol, Graham] Univ Washington, Seattle, WA 98195 USA.
[Pandey, Dilip K.] Univ Illinois, Chicago, IL USA.
[Paynter, Nina P.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Reeves, Matthew J.] Michigan State Univ, E Lansing, MI 48824 USA.
[Sorlie, Paul D.] NHLBI, NIH, Bethesda, MD USA.
[Stein, Joel] Columbia Univ, New York, NY 10027 USA.
[Towfighi, Amytis] Univ So Calif, Los Angeles, CA 90089 USA.
[Turner, Melanie B.] Amer Heart Assoc, Dallas, TX USA.
[Virani, Salim S.] Baylor Coll Med, Dept Vet Affairs, Houston, TX 77030 USA.
[Wong, Nathan D.] Univ Calif Irvine, Irvine, CA 92717 USA.
RP Go, AS (reprint author), Kaiser Permanente, Oakland, CA 94612 USA.
OI Mackey, Rachel/0000-0001-6088-2664; Matchar, David/0000-0003-3020-2108;
Turan, Tanya/0000-0001-5399-8845; Huffman, Mark/0000-0001-7412-2519;
Benjamin, Emelia/0000-0003-4076-2336; Virani, Salim/0000-0001-9541-6954;
Kissela, Brett/0000-0002-9773-4013
FU NCATS NIH HHS [UL1 TR001425]
NR 2
TC 2256
Z9 2326
U1 23
U2 268
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 JAN 21
PY 2014
VL 129
IS 3
BP E28
EP E292
DI 10.1161/01.cir.0000441139.02102.80
PG 267
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 292CV
UT WOS:000329880700002
PM 24352519
ER
PT J
AU Baranello, L
Kouzine, F
Levens, D
AF Baranello, Laura
Kouzine, Fedor
Levens, David
TI CTCF and cohesin cooperate to organize the 3D structure of the mammalian
genome
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Editorial Material
DE ``
ID GENE-EXPRESSION; CHROMATIN ARCHITECTURE; TRANSCRIPTION; DOMAINS; DNA
C1 [Baranello, Laura; Kouzine, Fedor; Levens, David] NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Levens, D (reprint author), NCI, Pathol Lab, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA.
EM levens@helix.nih.gov
RI Levens, David/C-9216-2009
OI Levens, David/0000-0002-7616-922X
NR 18
TC 8
Z9 8
U1 0
U2 10
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JAN 21
PY 2014
VL 111
IS 3
BP 889
EP 890
DI 10.1073/pnas.1321957111
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 292UQ
UT WOS:000329928400021
PM 24398527
ER
PT J
AU Martina, JA
Diab, HI
Lishu, L
Jeong-A, L
Patange, S
Raben, N
Puertollano, R
AF Martina, Jose A.
Diab, Heba I.
Lishu, Li
Jeong-A, Lim
Patange, Simona
Raben, Nina
Puertollano, Rosa
TI The Nutrient-Responsive Transcription Factor TFE3 Promotes Autophagy,
Lysosomal Biogenesis, and Clearance of Cellular Debris
SO SCIENCE SIGNALING
LA English
DT Article
ID MUCOLIPIDOSIS TYPE-IV; HOGG-DUBE-SYNDROME; IN-VIVO; POMPE DISEASE; RAG
GTPASES; OSTEOCLAST DEVELOPMENT; MEMBRANE-PROTEIN; NETWORK REVEALS;
FACTOR FAMILY; AMINO-ACIDS
AB The discovery of a gene network regulating lysosomal biogenesis and its transcriptional regulator transcription factor EB ( TFEB) revealed that cells monitor lysosomal function and respond to degradation requirements and environmental cues. We report the identification of transcription factor E3 ( TFE3) as another regulator of lysosomal homeostasis that induced expression of genes encoding proteins involved in autophagy and lysosomal biogenesis in ARPE- 19 cells in response to starvation and lysosomal stress. We found that in nutrient- replete cells, TFE3 was recruited to lysosomes through interaction with active Rag guanosine triphosphatases ( GTPases) and exhibited mammalian ( or mechanistic) target of rapamycin complex 1 ( mTORC1)- dependent phosphorylation. Phosphorylated TFE3 was retained in the cytosol through its interaction with the cytosolic chaperone 14- 3- 3. After starvation, TFE3 rapidly translocated to the nucleus and bound to the CLEAR elements present in the promoter region of many lysosomal genes, thereby inducing lysosomal biogenesis. Depletion of endogenous TFE3 entirely abolished the response of ARPE- 19 cells to starvation, suggesting that TFE3 plays a critical role in nutrient sensing and regulation of energy metabolism. Furthermore, overexpression of TFE3 triggered lysosomal exocytosis and resulted in efficient cellular clearance in a cellular model of a lysosomal storage disorder, Pompe disease, thus identifying TFE3 as a potential therapeutic target for the treatment of lysosomal disorders.
C1 [Martina, Jose A.; Diab, Heba I.; Patange, Simona; Puertollano, Rosa] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Lishu, Li; Jeong-A, Lim; Raben, Nina] NIAMSD, Lab Muscle Stem Cells & Gene Regulat, NIH, Bethesda, MD 20892 USA.
RP Puertollano, R (reprint author), NHLBI, Cell Biol Lab, NIH, 9000 Rockville Pike,Bldg 50-3537, Bethesda, MD 20892 USA.
EM puertolr@mail.nih.gov
RI Li, Lishu /J-3191-2015; di Ronza, Alberto/H-7674-2016
OI di Ronza, Alberto/0000-0002-9813-5143
FU NIH, National Heart, Lung, and Blood Institute
FX A. M., H. I. D., S. P., and R. P. were supported by the Intramural
Research Program of the NIH, National Heart, Lung, and Blood Institute.
L. J., L. L., and N. R. were supported part by the Intramural Research
Program of the National Institute of Arthritis and Musculoskeletal and
Skin Diseases of the NIH. L. J. and L. L. were supported in part by a
Cooperative Research and Development Agreement ( CRADA) between NIH and
Genzyme Corp.
NR 61
TC 63
Z9 63
U1 7
U2 24
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1945-0877
EI 1937-9145
J9 SCI SIGNAL
JI Sci. Signal.
PD JAN 21
PY 2014
VL 7
IS 309
AR ra9
DI 10.1126/scisignal.2004754
PG 15
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 292YL
UT WOS:000329938500003
PM 24448649
ER
PT J
AU Feng, MQ
Ho, M
AF Feng, Mingqian
Ho, Mitchell
TI Glypican-3 antibodies: A new therapeutic target for liver cancer
SO FEBS LETTERS
LA English
DT Review
DE Glypican-3 (GPC3); Hepatocellular carcinoma; Heparan sulfate
proteoglycan; HN3; GC33; YP7
ID HEPATOCELLULAR-CARCINOMA CELLS; GOLABI-BEHMEL-SYNDROME; DYSPLASTIC
NODULES; DIAGNOSTIC-VALUE; GLUTAMINE-SYNTHETASE; SEROLOGICAL MARKER;
IN-VIVO; EXPRESSION; GROWTH; OVERGROWTH
AB Glypican-3 (GPC3) is an emerging therapeutic target in hepatocellular carcinoma (HCC), even though the biological function of GPC3 remains elusive. Currently human (MDX-1414 and HN3) and humanized mouse (GC33 and YP7) antibodies that target GPC3 for HCC treatment are under different stages of preclinical or clinical development. Humanized mouse antibody GC33 is being evaluated in a phase II clinical trial. Human antibodies MDX-1414 and HN3 are under different stages of preclinical evaluation. Here, we summarize current evidence for GPC3 as a new target in liver cancer, discuss both its oncogenic function and its mode of actions for current antibodies, and evaluate potential challenges for GPC3-targeted anti-cancer therapies. Published by Elsevier B. V. on behalf of the Federation of European Biochemical Societies.
C1 [Feng, Mingqian; Ho, Mitchell] NCI, Antibody Therapy Sect, Mol Biol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
RP Ho, M (reprint author), NCI, Antibody Therapy Sect, Mol Biol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
EM homi@mail.nih.gov
RI Ho, Mitchell/F-5059-2015
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research. We thank the
NIH Fellows Editorial Board for editorial assistance. The content of
this publication does not necessarily reflect the views or policies of
the Department of Health and Human Services, nor does mention of trade
names, commercial products or organizations imply endorsement by the US
Government.
NR 58
TC 25
Z9 27
U1 3
U2 27
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0014-5793
EI 1873-3468
J9 FEBS LETT
JI FEBS Lett.
PD JAN 21
PY 2014
VL 588
IS 2
BP 377
EP 382
DI 10.1016/j.febslet.2013.10.002
PG 6
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 286XR
UT WOS:000329503100022
PM 24140348
ER
PT J
AU Allegra, CJ
Yothers, G
O'Connell, MJ
Roh, MS
Beart, RW
Petrelli, NJ
Lopa, SH
Sharif, S
Wolmark, N
AF Allegra, Carmen Joseph
Yothers, Greg
O'Connell, Michael J.
Roh, Mark S.
Beart, Robert W.
Petrelli, Nicholas J.
Lopa, Samia H.
Sharif, Saima
Wolmark, Norman
TI Neoadjuvant therapy for rectal cancer: Mature results from NSABP
protocol R-04
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Gastrointestinal Cancers Symposium
CY JAN 16-18, 2014
CL San Francisco, CA
C1 Natl Surg Adjuvant Breast & Bowel Project, Gainesville, FL USA.
Univ Florida, Gainesville, FL USA.
Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA.
Biostat Ctr, Pittsburgh, PA USA.
Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA.
Natl Surg Adjuvant Breast & Bowel Project, Operat Off, Pittsburgh, PA USA.
MD Anderson Canc Ctr Orlando, Pittsburgh, PA USA.
Natl Surg Adjuvant Breast & Bowel Project, Gelndale, CA USA.
Glendale Mem Hosp, Gelndale, CA USA.
Christiana Care Hlth Syst, Natl Surg Adjuvant Breast & Bowel Project, Newark, DE USA.
Christiana Care Hlth Syst, Helen F Graham Canc Ctr, Newark, DE USA.
Univ Pittsburgh, Grad Sch Publ Hlth, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA.
Univ Pittsburgh, Grad Sch Publ Hlth, Natl Surg Adjuvant Breast & Bowel Project, Biostat Ctr, Pittsburgh, PA USA.
Allegheny Gen Hosp, Pittsburgh, PA 15212 USA.
Allegheny Gen Hosp, Allegheny Canc Ctr, Pittsburgh, PA 15212 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JAN 20
PY 2014
VL 32
IS 3
SU S
MA 390
PG 1
WC Oncology
SC Oncology
GA AE0UQ
UT WOS:000333682100387
ER
PT J
AU Dasari, A
Phan, A
Gupta, S
Hess, KR
Culotta, KS
Rashid, A
Yeung, SJ
Chen, HLX
Dong, M
Halperin, DM
Subbiah, IM
Meric-Bernstam, F
Yao, JC
AF Dasari, Arvind
Phan, Alexandria
Gupta, Sanjay
Hess, Kenneth R.
Culotta, Kirk Salvatore
Rashid, Asif
Yeung, S. J.
Chen, Helen X.
Dong, Mei
Halperin, Daniel M.
Subbiah, Ishwaria Mohan
Meric-Bernstam, Funda
Yao, James C.
TI A phase I study of the anti-IGF-1R monoclonal antibody (MoAb), IMC-A12
(I), and everolimus (E) in well-differentiated neuroendocrine tumors (WD
NET)
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Gastrointestinal Cancers Symposium
CY JAN 16-18, 2014
CL San Francisco, CA
C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Houston Methodist Hosp, Ctr Canc, Houston, TX USA.
Univ Texas MD Anderson Canc Ctr, Dept Radiol, Houston, TX 77030 USA.
NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
Univ Texas MD Anderson Canc Ctr, Div Canc Med, Houston, TX 77030 USA.
Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Div Canc Med, Houston, TX 77030 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JAN 20
PY 2014
VL 32
IS 3
SU S
MA 232
PG 1
WC Oncology
SC Oncology
GA AE0UQ
UT WOS:000333682100235
ER
PT J
AU Duffy, AG
Ma, C
Ulahannan, SV
Fioravanti, S
Venkatesan, A
Turkbey, IB
Choyke, PL
Trepel, JB
Cao, L
Compton, K
Figg, WD
Greten, TF
AF Duffy, Austin G.
Ma, Chi
Ulahannan, Susanna Varkey
Fioravanti, Suzanne
Venkatesan, Aradhana
Turkbey, Ismail B.
Choyke, Peter L.
Trepel, Jane B.
Cao, Liang
Compton, Kathryn
Figg, William Douglas
Greten, Tim F.
TI TRC105 for the treatment of hepatocellular carcinoma: Preclinical data
and preliminary results from two clinical trials evaluating monotherapy
and combination with sorafenib
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Gastrointestinal Cancers Symposium
CY JAN 16-18, 2014
CL San Francisco, CA
C1 NCI, NIH, Bethesda, MD 20892 USA.
NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
RI Greten, Tim/B-3127-2015; Figg Sr, William/M-2411-2016
OI Greten, Tim/0000-0002-0806-2535;
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JAN 20
PY 2014
VL 32
IS 3
SU S
MA 211
PG 1
WC Oncology
SC Oncology
GA AE0UQ
UT WOS:000333682100214
ER
PT J
AU El-Khoueiry, AB
O'Donnell, R
Mack, PC
Blanchard, S
Bahary, N
Jiang, YX
Yen, Y
Wright, JJ
Chen, H
Lenz, HJ
Gandara, DR
AF El-Khoueiry, Anthony B.
O'Donnell, Robert
Mack, Philip C.
Blanchard, Suzette
Bahary, Nathan
Jiang, Yixing
Yen, Yun
Wright, John Joseph
Chen, Helen
Lenz, Heinz-Josef
Gandara, David R.
TI A phase I trial of cixutumumab (C) (IMC-A12) and sorafenib (S) for
treatment of advanced hepatocellular carcinoma (HCC)
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Gastrointestinal Cancers Symposium
CY JAN 16-18, 2014
CL San Francisco, CA
C1 USC Norris Comprehens Canc Ctr, Los Angeles, CA USA.
Univ Calif Davis, Sacramento, CA 95817 USA.
City Hope Natl Med Ctr, Duarte, CA USA.
Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
Univ Maryland, Baltimore, MD 21201 USA.
City Hope Canc Ctr, Beckman Res Inst, Duarte, CA USA.
NCI, NIH, Bethesda, MD 20892 USA.
UC Davis Comprehens Canc Ctr, Sacramento, CA USA.
NR 0
TC 0
Z9 0
U1 1
U2 5
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 JAN 20
PY 2014
VL 32
IS 3
SU S
MA 293
PG 2
WC Oncology
SC Oncology
GA AE0UQ
UT WOS:000333682100295
ER
PT J
AU George, TJ
Ivey, AM
Daily, KC
Dang, LH
Watson, S
Granicz, R
Tormes, K
Lu, XM
Liu, C
Allegra, CJ
Behrns, K
Hughes, SJ
Ogunwobi, OO
Trevino, JG
AF George, Thomas J.
Ivey, Alison Marguerite
Daily, Karen Colleen
Dang, Long H.
Watson, Scott
Granicz, Renee
Tormes, Kevin
Lu, Xiaomin
Liu, Chen
Allegra, Carmen Joseph
Behrns, Kevin
Hughes, Steven J.
Ogunwobi, Olorunseun Olatunji
Trevino, Jose Gilberto
TI Src inhibition through a phase II study of 5-fluorouracil, oxaliplatin,
plus dasatinib (FOLFOX-D) in first-line metastatic pancreatic
adenocarcinoma
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Gastrointestinal Cancers Symposium
CY JAN 16-18, 2014
CL San Francisco, CA
C1 Univ Florida, Gainesville, FL USA.
Univ Florida, Natl Surg Adjuvant Breast & Bowel Project, Gainesville, FL USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JAN 20
PY 2014
VL 32
IS 3
SU S
MA 319
PG 1
WC Oncology
SC Oncology
GA AE0UQ
UT WOS:000333682100320
ER
PT J
AU Hembrough, TA
Liao, WL
Thyparambil, S
Henderson, L
Rambo, B
Cecchi, F
Bottaro, DP
Darfler, M
Xu, P
Xiao, SY
Zhao, L
Veenstra, TD
Burrows, J
Catenacci, DVT
AF Hembrough, Todd A.
Liao, Wei-Li
Thyparambil, Sheeno
Henderson, Les
Rambo, Brittany
Cecchi, Fabiola
Bottaro, Donald P.
Darfler, Marlene
Xu, Peng
Xiao, Shu-Yuan
Zhao, Lei
Veenstra, Timothy D.
Burrows, Jon
Catenacci, Daniel Virgil Thomas
TI Quantification of MET expression using mass spectrometry (MS): Assay
precision and stability in FFPE tumor tissue
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Gastrointestinal Cancers Symposium
CY JAN 16-18, 2014
CL San Francisco, CA
C1 OncoPlex Diagnost, Rockville, MD USA.
Univ Chicago, Chicago, IL 60637 USA.
NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
NCI, NIH, Bethesda, MD 20892 USA.
Univ Chicago, Dept Med, Chicago, IL 60637 USA.
Univ Chicago, Dept Pathol, Chicago, IL 60637 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JAN 20
PY 2014
VL 32
IS 3
SU S
MA 16
PG 1
WC Oncology
SC Oncology
GA AE0UQ
UT WOS:000333682100025
ER
PT J
AU Hubbard, JM
Kim, GP
Borad, MJ
Qin, R
Lensing, J
Wright, JJ
Erlichman, C
Grothey, A
AF Hubbard, Joleen Marie
Kim, George P.
Borad, Mitesh J.
Qin, Rui
Lensing, Janet
Wright, John Joseph
Erlichman, Charles
Grothey, Axel
TI Phase I trial of FOLFIRI in combination with sorafenib and bevacizumab
in patients with advanced gastrointestinal malignancies.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Gastrointestinal Cancers Symposium
CY JAN 16-18, 2014
CL San Francisco, CA
C1 Mayo Clin, Rochester, MN USA.
Mayo Clin, Jacksonville, FL 32224 USA.
Mayo Clin, Scottsdale, AZ USA.
NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JAN 20
PY 2014
VL 32
IS 3
SU S
MA 551
PG 1
WC Oncology
SC Oncology
GA AE0UQ
UT WOS:000333682100541
ER
PT J
AU Kelly, RJ
Pastan, I
Cowan, ML
Montgomery, E
Hassan, R
Alewine, CC
Xiang, LM
Illei, PB
AF Kelly, Ronan Joseph
Pastan, Ira
Cowan, Morgan L.
Montgomery, Elizabeth
Hassan, Raffit
Alewine, Christine Campo
Xiang, Laiman
Illei, Peter B.
TI Mesothelin expression in patients as a novel target in gastric cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Gastrointestinal Cancers Symposium
CY JAN 16-18, 2014
CL San Francisco, CA
C1 Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA.
NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
Johns Hopkins Univ Hosp, Dept Pathol, Baltimore, MD USA.
NCI, NIH, Bethesda, MD 20892 USA.
NCI, Highland, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JAN 20
PY 2014
VL 32
IS 3
SU S
MA 61
PG 1
WC Oncology
SC Oncology
GA AE0UQ
UT WOS:000333682100067
ER
PT J
AU Kim, HK
Park, JW
Green, JE
AF Kim, Hark K.
Park, Jun Won
Green, Jeffrey E.
TI Relationship of novel genetically engineered mouse and the
epithelial-mesenchymal transition in the metastastic progression of
gastric cancers
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Gastrointestinal Cancers Symposium
CY JAN 16-18, 2014
CL San Francisco, CA
C1 Natl Canc Ctr, Ctr Gastr Canc, Goyang, South Korea.
NIH, Lab Canc Biol & Genet, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JAN 20
PY 2014
VL 32
IS 3
SU S
MA 3
PG 1
WC Oncology
SC Oncology
GA AE0UQ
UT WOS:000333682100014
ER
PT J
AU Le, DT
Wang-Gillam, A
Picozzi, V
Greten, TF
Crocenzi, TS
Springett, GM
Morse, M
Zeh, H
Cohen, DJ
Fine, RL
Onners, B
Uram, JN
Laheru, D
Murphy, A
Skoble, J
Lemmens, E
Grous, JJ
Dubensky, T
Brockstedt, DG
Jaffee, EM
AF Le, Dung T.
Wang-Gillam, Andrea
Picozzi, Vincent, Jr.
Greten, Tim F.
Crocenzi, Todd S.
Springett, Gregory M.
Morse, Michael
Zeh, Herbert
Cohen, Deirdre Jill
Fine, Robert Lance
Onners, Beth
Uram, Jennifer N.
Laheru, Dan
Murphy, Aimee
Skoble, Justin
Lemmens, Ed
Grous, John J.
Dubensky, Thomas
Brockstedt, Dirk G.
Jaffee, Elizabeth M.
TI A phase 2, randomized trial of GVAX pancreas and CRS-207 immunotherapy
versus GVAX alone in patients with metastatic pancreatic adenocarcinoma:
Updated results
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Gastrointestinal Cancers Symposium
CY JAN 16-18, 2014
CL San Francisco, CA
C1 Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA.
Washington Univ, Sch Med, St Louis, MO USA.
Virginia Mason Med Ctr, Seattle, WA 98101 USA.
NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
Providence Canc Ctr, Portland, OR USA.
Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA.
Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA.
Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
NYU, Inst Canc, New York, NY USA.
Columbia Univ, New York, NY USA.
Aduro BioTech Inc, Berkeley, CA USA.
RI Greten, Tim/B-3127-2015
OI Greten, Tim/0000-0002-0806-2535
NR 0
TC 3
Z9 4
U1 0
U2 2
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JAN 20
PY 2014
VL 32
IS 3
SU S
MA 177
PG 1
WC Oncology
SC Oncology
GA AE0UQ
UT WOS:000333682100181
ER
PT J
AU Shiovitz, S
Hsu, L
Qu, CH
Harrison, TA
Berndt, S
Brenner, H
Casey, G
Chan, AT
Chang-Claude, J
Le Marchand, L
Newcomb, PA
Potter, JD
Schoen, RE
Slattery, ML
White, E
Peters, U
Grady, WM
Consortium, G
AF Shiovitz, Stacey
Hsu, Li
Qu, Conghui
Harrison, Tabitha A.
Berndt, Sonja
Brenner, Hermann
Casey, Graham
Chan, Andrew T.
Chang-Claude, Jenny
Le Marchand, Loic
Newcomb, Polly A.
Potter, John D.
Schoen, Robert E.
Slattery, Martha L.
White, Emily
Peters, Ulrike
Grady, William M.
Consortium, G. E. C. C. O.
TI DCC and RET pathway analysis to identify factors associated with
advanced colorectal cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Gastrointestinal Cancers Symposium
CY JAN 16-18, 2014
CL San Francisco, CA
C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
NCI, NIH, Bethesda, MD 20892 USA.
German Canc Res Ctr, Heidelberg, Germany.
Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Univ Hawaii, Honolulu, HI 96822 USA.
Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
Univ Utah, Salt Lake City, UT USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JAN 20
PY 2014
VL 32
IS 3
SU S
MA 457
PG 1
WC Oncology
SC Oncology
GA AE0UQ
UT WOS:000333682100450
ER
PT J
AU Ulahannan, SV
Duffy, AG
Kish, JK
McGlynn, K
Rahma, OE
Greten, TF
Altekruse, S
AF Ulahannan, Susanna Varkey
Duffy, Austin G.
Kish, Jonathan K.
McGlynn, Katherine
Rahma, Osama E.
Greten, Tim F.
Altekruse, Sean
TI Disconnect between earlier presentation patterns and application of
curative treatments in HCC
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Gastrointestinal Cancers Symposium
CY JAN 16-18, 2014
CL San Francisco, CA
C1 NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NCI, NIH, Bethesda, MD 20892 USA.
NCI, Rockville, MD USA.
NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RI Greten, Tim/B-3127-2015
OI Greten, Tim/0000-0002-0806-2535
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JAN 20
PY 2014
VL 32
IS 3
SU S
MA 187
PG 1
WC Oncology
SC Oncology
GA AE0UQ
UT WOS:000333682100191
ER
PT J
AU Yothers, G
George, TJ
Petrelli, NJ
O'Connell, MJ
Beart, RW
Allegra, CJ
Roh, MS
Lopa, SH
Sharif, S
Wolmark, N
AF Yothers, Greg
George, Thomas J.
Petrelli, Nicholas J.
O'Connell, Michael J.
Beart, Robert W.
Allegra, Carmen Joseph
Roh, Mark S.
Lopa, Samia H.
Sharif, Saima
Wolmark, Norman
TI Neoadjuvant rectal cancer (RC) score to predict survival: Potential
surrogate endpoint for early-phase trials
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Gastrointestinal Cancers Symposium
CY JAN 16-18, 2014
CL San Francisco, CA
C1 Natl Surg Adjuvant Breast & Bowel Project, Biostat Ctr, Pittsburgh, PA USA.
Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA.
Univ Florida, Gainesville, FL USA.
Christiana Care Hlth Syst, Natl Surg Adjuvant Breast & Bowel Project, Newark, DE USA.
Christiana Care Hlth Syst, Helen F Graham Canc Ctr, Newark, DE USA.
Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA.
Natl Surg Adjuvant Breast & Bowel Project, Gelndale, CA USA.
Glendale Mem Hosp, Gelndale, CA USA.
Natl Surg Adjuvant Breast & Bowel Project, Gainesville, FL USA.
MD Anderson Canc Ctr Orlando, Pittsburgh, PA USA.
Univ Pittsburgh, Grad Sch Publ Hlth, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA.
Univ Pittsburgh, Grad Sch Publ Hlth, Natl Surg Adjuvant Breast & Bowel Project, Biostat Ctr, Pittsburgh, PA USA.
Allegheny Gen Hosp, Pittsburgh, PA 15212 USA.
Allegheny Gen Hosp, Allegheny Canc Ctr, Pittsburgh, PA 15212 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JAN 20
PY 2014
VL 32
IS 3
SU S
MA 384
PG 1
WC Oncology
SC Oncology
GA AE0UQ
UT WOS:000333682100384
ER
PT J
AU Liao, GJW
Gronowski, AM
Zhao, Z
AF Liao, Gary J. W.
Gronowski, Ann M.
Zhao, Zhen
TI Non-invasive prenatal testing using cell-free fetal DNA in maternal
circulation
SO CLINICA CHIMICA ACTA
LA English
DT Review
DE Non-invasive prenatal testing; Cell-free fetal DNA; Fetal sex
assessment; RhD genotyping; Fetal chromosomal aneuploidy; Single-gene
disorders
ID CONGENITAL ADRENAL-HYPERPLASIA; TRISOMY NIFTY TEST; SEX DETERMINATION;
HUNTINGTON-DISEASE; CHROMOSOMAL ANEUPLOIDIES; MONOGENIC DISEASES;
EARLY-PREGNANCY; NUCLEIC-ACIDS; DIGITAL PCR; PLASMA
AB The identification of cell-free fetal DNA (cffDNA) in maternal circulation has made non-invasive prenatal testing (NIPT) possible. Maternal plasma cell free DNA is a mixture of maternal and fetal DNA, of which, fetal DNA represents a minor population in maternal plasma. Therefore, methods with high sensitivity and precision are required to detect and differentiate fetal DNA from the large background of maternal DNA. In recent years, technical advances in the molecular analysis of fetal DNA (e.g., digital PCR and massively parallel sequencing (MPS)) has enabled the successful implementation of noninvasive testing into clinical practice, such as fetal sex assessment, RhD genotyping, and fetal chromosomal aneuploidy detection. With the ability to decipher the entire fetal genome from maternal plasma DNA, we foresee that an increased number of non-invasive prenatal tests will be available for detecting many single-gene disorders in the near future. This review briefly summarizes the technical aspects of the NIPT and application of NIPT in clinical practice. (C) 2013 Elsevier B.V. All rights reserved.
C1 [Liao, Gary J. W.] Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Ctr Res Circulating Fetal Nucle Acids, Shatin, Hong Kong, Peoples R China.
[Liao, Gary J. W.] Chinese Univ Hong Kong, Dept Chem Pathol, Shatin, Hong Kong, Peoples R China.
[Gronowski, Ann M.] Washington Univ, Sch Med, Div Lab & Genom Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
[Zhao, Zhen] NIH, Dept Lab Med, Bethesda, MD 20892 USA.
RP Gronowski, AM (reprint author), 660 South Euclid Ave,Box 8118, St Louis, MO 63110 USA.
EM gronowski@wustl.edu
NR 77
TC 13
Z9 16
U1 5
U2 47
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0009-8981
EI 1873-3492
J9 CLIN CHIM ACTA
JI Clin. Chim. Acta
PD JAN 20
PY 2014
VL 428
BP 44
EP 50
DI 10.1016/j.cca.2013.10.007
PG 7
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA AB3HV
UT WOS:000331682800008
PM 24482806
ER
PT J
AU Sholukh, AM
Byrareddy, SN
Shanmuganathan, V
Hemashettar, G
Lakhashe, SK
Rasmussen, RA
Watkins, JD
Vyas, HK
Thorat, S
Brandstoetter, T
Mukhtar, MM
Yoon, JK
Novembre, FJ
Villinger, F
Landucci, G
Forthal, DN
Ratcliffe, S
Tuero, I
Robert-Guroff, M
Polonis, VR
Bilska, M
Montefiori, DC
Johnson, WE
Ertl, HC
Ruprecht, RM
AF Sholukh, Anton M.
Byrareddy, Siddappa N.
Shanmuganathan, Vivekanandan
Hemashettar, Girish
Lakhashe, Samir K.
Rasmussen, Robert A.
Watkins, Jennifer D.
Vyas, Hemant K.
Thorat, Swati
Brandstoetter, Tania
Mukhtar, Muhammad M.
Yoon, John K.
Novembre, Francis J.
Villinger, Francois
Landucci, Gary
Forthal, Donald N.
Ratcliffe, Sarah
Tuero, Iskra
Robert-Guroff, Marjorie
Polonis, Victoria R.
Bilska, Miroslawa
Montefiori, David C.
Johnson, Welkin E.
Ertl, Hildegund C.
Ruprecht, Ruth M.
TI Passive immunization of macaques with polyclonal anti-SHIV IgG against a
heterologous tier 2 SHIV: outcome depends on IgG dose
SO RETROVIROLOGY
LA English
DT Article
DE Macaque model; Heterologous R5 SHIV clade C challenge; SHIVIG; Passive
immunization; Enhancement of infection; Non-human primate model
ID HIV-1/SIV CHIMERIC VIRUS; CLADE-C INFECTION; NEUTRALIZING ANTIBODIES;
HIV-INFECTION; RHESUS MACAQUES; NONNEUTRALIZING ANTIBODIES;
REPLICATION-COMPETENT; ENVELOPE GLYCOPROTEIN; MEDIATED ENHANCEMENT;
VACCINE DEVELOPMENT
AB Background: A key goal for HIV-1 envelope immunogen design is the induction of cross-reactive neutralizing antibodies (nAbs). As AIDS vaccine recipients will not be exposed to strains exactly matching any immunogens due to multiple HIV-1 quasispecies circulating in the human population worldwide, heterologous SHIV challenges are essential for realistic vaccine efficacy testing in primates. We assessed whether polyclonal IgG, isolated from rhesus monkeys (RMs) with high-titer nAbs (termed SHIVIG), could protect RMs against the R5-tropic tier-2 SHIV-2873Nip, which was heterologous to the viruses or HIV-1 envelopes that had elicited SHIVIG.
Results: SHIVIG demonstrated binding to HIV Gag, Tat, and Env of different clades and competed with the broadly neutralizing antibodies b12, VRC01, 4E10, and 17b. SHIVIG neutralized tier 1 and tier 2 viruses, including SHIV-2873Nip. NK-cell depletion decreased the neutralizing activity of SHIVIG 20-fold in PBMC assays. Although SHIVIG neutralized SHIV-2873Nip in vitro, this polyclonal IgG preparation failed to prevent acquisition after repeated intrarectal low-dose virus challenges, but at a dose of 400 mg/kg, it significantly lowered peak viremia (P = 0.001). Unexpectedly, single-genome analysis revealed a higher number of transmitted variants at the low dose of 25 mg/kg, implying increased acquisition at low SHIVIG levels. In vitro, SHIVIG demonstrated complement-mediated Ab-dependent enhancement of infection (C'-ADE) at concentrations similar to those observed in plasmas of RMs treated with 25 mg/kg of SHIVIG.
Conclusion: Our primate model data suggest a dual role for polyclonal anti-HIV-1 Abs depending on plasma levels upon virus encounter.
C1 [Sholukh, Anton M.; Lakhashe, Samir K.; Vyas, Hemant K.; Mukhtar, Muhammad M.; Ruprecht, Ruth M.] Texas Biomed Res Inst, Dept Virol & Immunol, San Antonio, TX 78245 USA.
[Sholukh, Anton M.; Byrareddy, Siddappa N.; Shanmuganathan, Vivekanandan; Hemashettar, Girish; Lakhashe, Samir K.; Rasmussen, Robert A.; Watkins, Jennifer D.; Vyas, Hemant K.; Thorat, Swati; Brandstoetter, Tania; Mukhtar, Muhammad M.; Yoon, John K.; Ruprecht, Ruth M.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Sholukh, Anton M.; Byrareddy, Siddappa N.; Lakhashe, Samir K.; Rasmussen, Robert A.; Watkins, Jennifer D.; Vyas, Hemant K.; Thorat, Swati; Mukhtar, Muhammad M.; Ruprecht, Ruth M.] Harvard Univ, Sch Med, Boston, MA USA.
[Novembre, Francis J.; Villinger, Francois] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA.
[Novembre, Francis J.] Emory Univ, Dept Microbiol & Immunol, Atlanta, GA 30322 USA.
[Byrareddy, Siddappa N.; Villinger, Francois] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA.
[Landucci, Gary; Forthal, Donald N.] Univ Calif Irvine, Sch Med, Dept Med, Div Infect Dis, Irvine, CA 92717 USA.
[Ratcliffe, Sarah] Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Tuero, Iskra; Robert-Guroff, Marjorie] NCI, Ctr Canc Res, Vaccine Branch, Bethesda, MD 20892 USA.
[Polonis, Victoria R.] Walter Reed Army Inst Res, Mil HIV Res Program, Silver Spring, MD USA.
[Bilska, Miroslawa; Montefiori, David C.] Duke Univ, Sch Med, Dept Surg, Durham, NC USA.
[Johnson, Welkin E.] Boston Coll, Dept Biol, Boston, MA USA.
[Ertl, Hildegund C.] Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA.
RP Ruprecht, RM (reprint author), Texas Biomed Res Inst, Dept Virol & Immunol, POB 760549, San Antonio, TX 78245 USA.
EM rruprecht@txbiomed.org
RI Lakhashe, Samir/F-1150-2014;
OI Byrareddy, Siddappa /0000-0002-7423-1763; Ratcliffe,
Sarah/0000-0002-6644-8284
FU NIH [P01 AI082282, R37 AI034266, R01 DE023049, P01 AI048240, R01
AI083118, HHSN27201100016C]; Henry M. Jackson Foundation for the
Advancement of Military Medicine, Inc. [W81XWH-07-2-0067]; U.S.
Department of Defense (DOD) [W81XWH-07-2-0067]; Intramural Research
Program of the NIH, National Cancer Institute; Office of Research
Infrastructure Programs/OD [P51OD11107]
FX We thank Dr. J. Mascola for providing mAb VRC01, Dr. S.-L. Hu for
providing SHIV-1157ip Env proteins, Dr. W. Marasco for providing mAb
Fm-6, Dr. C. Ochsenbauer for providing pNL-LucR.T2A plasmid, P.
Ehrenberg for production of the infectious molecular clones (GS 014 and
GS 020), Dr. J. Hoxie for providing SupT1.R5 cells, and Juan Esquivel
for technical help with the manuscript. This work was supported by NIH
grants P01 AI082282 to RMR, SR and HCE, R37 AI034266, R01 DE023049 and
P01 AI048240 to RMR, R01 AI083118 to WEJ, and HHSN27201100016C to DCM as
well as by a cooperative agreement (W81XWH-07-2-0067) between the Henry
M. Jackson Foundation for the Advancement of Military Medicine, Inc.,
and the U.S. Department of Defense (DOD) to VRP. This project was also
funded in part by the Intramural Research Program of the NIH, National
Cancer Institute, to MR-G and by the Office of Research Infrastructure
Programs/OD P51OD11107 to the YNPRC. The authors have no conflicting
financial interests.
NR 46
TC 8
Z9 8
U1 0
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-4690
J9 RETROVIROLOGY
JI Retrovirology
PD JAN 20
PY 2014
VL 11
AR 8
DI 10.1186/1742-4690-11-8
PG 15
WC Virology
SC Virology
GA AB3OT
UT WOS:000331700800001
PM 24444350
ER
PT J
AU Virgo, KS
Lerro, CC
Klabunde, CN
Earle, C
Ganz, PA
AF Virgo, Katherine S.
Lerro, Catherine C.
Klabunde, Carrie N.
Earle, Craig
Ganz, Patricia A.
TI Is It Better to Transfer Long-Term Cancer Survivors to General
Practitioners or Develop Clinics for Long-Term Survivors Within the
Cancer Centers? Reply
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Letter
C1 [Virgo, Katherine S.] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.
[Lerro, Catherine C.] Yale Univ, Sch Publ Hlth, New Haven, CT USA.
[Klabunde, Carrie N.] NCI, Bethesda, MD 20892 USA.
[Earle, Craig] Univ Toronto, Inst Clin Evaluat Sci, Toronto, ON, Canada.
[Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Fielding Sch Publ Hlth, Los Angeles, CA 90024 USA.
[Ganz, Patricia A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
RP Virgo, KS (reprint author), Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.
FU PHS HHS [24297952]
NR 0
TC 4
Z9 4
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JAN 20
PY 2014
VL 32
IS 3
BP 258
EP 258
DI 10.1200/JCO.2013.52.7622
PG 1
WC Oncology
SC Oncology
GA 302TN
UT WOS:000330627900018
PM 24297957
ER
PT J
AU Tiruvannamalai-Annamalai, R
Armant, DR
Matthew, HWT
AF Tiruvannamalai-Annamalai, Ramkumar
Armant, David Randall
Matthew, Howard W. T.
TI A Glycosaminoglycan Based, Modular Tissue Scaffold System for Rapid
Assembly of Perfusable, High Cell Density, Engineered Tissues
SO PLOS ONE
LA English
DT Article
ID MESENCHYMAL STEM-CELLS; SMOOTH-MUSCLE-CELLS; ACUTE LIVER-FAILURE;
VASCULAR ENDOTHELIAL-CELLS; HUMAN SKIN EQUIVALENT; IN-VITRO; ARTICULAR
CHONDROCYTES; SANDWICH CONFIGURATION; NERVE REGENERATION; VESSEL
MATURATION
AB The limited ability to vascularize and perfuse thick, cell-laden tissue constructs has hindered efforts to engineer complex tissues and organs, including liver, heart and kidney. The emerging field of modular tissue engineering aims to address this limitation by fabricating constructs from the bottom up, with the objective of recreating native tissue architecture and promoting extensive vascularization. In this paper, we report the elements of a simple yet efficient method for fabricating vascularized tissue constructs by fusing biodegradable microcapsules with tunable interior environments. Parenchymal cells of various types, (i.e. trophoblasts, vascular smooth muscle cells, hepatocytes) were suspended in glycosaminoglycan (GAG) solutions (4%/1.5% chondroitin sulfate/carboxymethyl cellulose, or 1.5 wt% hyaluronan) and encapsulated by forming chitosan-GAG polyelectrolyte complex membranes around droplets of the cell suspension. The interior capsule environment could be further tuned by blending collagen with or suspending microcarriers in the GAG solution These capsule modules were seeded externally with vascular endothelial cells (VEC), and subsequently fused into tissue constructs possessing VEC-lined, inter-capsule channels. The microcapsules supported high density growth achieving clinically significant cell densities. Fusion of the endothelialized, capsules generated three dimensional constructs with an embedded network of interconnected channels that enabled long-term perfusion culture of the construct. A prototype, engineered liver tissue, formed by fusion of hepatocyte-containing capsules exhibited urea synthesis rates and albumin synthesis rates comparable to standard collagen sandwich hepatocyte cultures. The capsule based, modular approach described here has the potential to allow rapid assembly of tissue constructs with clinically significant cell densities, uniform cell distribution, and endothelialized, perfusable channels.
C1 [Tiruvannamalai-Annamalai, Ramkumar; Matthew, Howard W. T.] Wayne State Univ, Dept Biomed Engn, Detroit, MI 48202 USA.
[Armant, David Randall] Wayne State Univ, Dept Obstet, Detroit, MI USA.
[Armant, David Randall] Wayne State Univ, Dept Gynecol, Detroit, MI USA.
[Armant, David Randall] NICHHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
[Matthew, Howard W. T.] Wayne State Univ, Dept Chem Engn & Mat Sci, Detroit, MI USA.
RP Matthew, HWT (reprint author), Wayne State Univ, Dept Biomed Engn, Detroit, MI 48202 USA.
EM hmatthew@wayne.edu
OI Armant, D. Randall/0000-0001-5904-9325; Tiruvannamalai Annamalai,
Ramkumar/0000-0002-9880-3973
FU DRICTR award from Wayne State University; National Science Foundation
[CBET-1067323]; National Institutes of Health [HD067629]
FX Funding for these studies was provided by a DRICTR award from Wayne
State University, and grant awards from the National Science Foundation
(CBET-1067323) and the National Institutes of Health (HD067629). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 72
TC 10
Z9 10
U1 4
U2 45
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 JAN 20
PY 2014
VL 9
IS 1
AR e84287
DI 10.1371/journal.pone.0084287
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 297FH
UT WOS:000330240500014
PM 24465401
ER
PT J
AU Pereira, LE
Clark, J
Grznarova, P
Wen, XY
LaCasse, R
Ruml, T
Spearman, P
Hunter, E
AF Pereira, Lara E.
Clark, Jasmine
Grznarova, Petra
Wen, Xiaoyun
LaCasse, Rachel
Ruml, Tomas
Spearman, Paul
Hunter, Eric
TI Direct evidence for intracellular anterograde co-transport of M-PMV Gag
and Env on microtubules
SO VIROLOGY
LA English
DT Article
DE M-PMV; Envelope; Gag; Anterograde transport; Cytoskeleton; Live
cell-imaging
ID PFIZER MONKEY VIRUS; PERICENTRIOLAR RECYCLING ENDOSOME;
TARGETING-RETENTION SIGNAL; MATRIX PROTEIN; D RETROVIRUSES; IN-VITRO;
TRANSPORT; POLYPROTEIN; TRAFFICKING; MEMBRANE
AB The intracellular transport of Mason-Pfizer monkey virus (M-PMV) assembled capsids from the pericentriolar region to the plasma membrane (PM) requires trafficking of envelope glycoprotein (Env) to the assembly site via the recycling endosome. However, it is unclear if Env-containing vesicles play a direct role in trafficking capsids to the PM. Using live cell microscopy, we demonstrate, for the first time, anterograde co-transport of Gag and Env. Nocodazole disruption of microtubules had differential effects on Gag and Env trafficking, with pulse-chase assays showing a delayed release of Env-deficient virions. Particle tracking demonstrated an initial loss of linear movement of GFP-tagged capsids and mCherry-tagged Env, followed by renewed movement of Gag but not Env at 4 h post-treatment. Thus, while delayed capsid trafficking can occur in the absence of microtubules, efficient anterograde transport of capsids appears to be mediated by microtubule-associated Env-containing vesicles. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Pereira, Lara E.; Clark, Jasmine; Hunter, Eric] Emory Vaccine Ctr, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA.
[Grznarova, Petra; Ruml, Tomas] Inst Chem Technol, Dept Biochem & Microbiol, CR-16628 Prague, Czech Republic.
[Wen, Xiaoyun; Spearman, Paul] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA 30322 USA.
[LaCasse, Rachel] NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA.
RP Hunter, E (reprint author), Emory Vaccine Ctr, Yerkes Natl Primate Res Ctr, 954 Gatewood Rd NE, Atlanta, GA 30329 USA.
EM vvg3@cdc.gov; jrainey@emory.edu; Petra.Grznarova@vscht.cz;
xiaoyun.wen@emory.edu; RLaCasse@niaid.nih.gov; Tomas.Ruml@vscht.cz;
paul.spearman@emory.edu; eric.hunter2@emory.edu
FU NIH [CA-27834]; National Cancer Institute and Czech Ministry of
Education [LN12011]; Czech Science Foundation [P302/12/1895]; American
Society for Microbiology Robert D. Watkins Fellowship
FX This work was supported by the NIH Grant CA-27834 from the National
Cancer Institute and Czech Ministry of Education Grant LN12011 and by
Czech Science Foundation Grant P302/12/1895. J. Clark was the recipient
of an American Society for Microbiology Robert D. Watkins Fellowship. We
thank the James B. Pendleton Charitable Trust for the contribution of
advanced imaging equipment utilized in the experiments in this
manuscript. We thank Dr. Jan Lipov, Dr. Greg Melikian, and Dr. Joseph
Roland for helpful discussions. We also thank Pavel Ulbrich (Institute
of Chemical Technology, Prague, Czech Republic) and Eileen Breding
(Yerkes National Primate Research Center, Atlanta GA) for excellent
advice and assistance with transmission electron microscopy, and the
Robert P. Apkarian Integrated Electron Microscopy Core of Emory
University for sample preparations. EH is a Georgia Research Alliance
Eminent Scholar. JC is an American Society for Microbiology Robert D.
Watkins fellow.
NR 39
TC 4
Z9 4
U1 0
U2 10
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD JAN 20
PY 2014
VL 449
BP 109
EP 119
DI 10.1016/j.virol.2013.11.006
PG 11
WC Virology
SC Virology
GA 295CL
UT WOS:000330094100013
PM 24418544
ER
PT J
AU Americo, JL
Sood, CL
Cotter, CA
Vogel, JL
Kristie, TM
Moss, B
Earl, PL
AF Americo, Jeffrey L.
Sood, Cindy L.
Cotter, Catherine A.
Vogel, Jodi L.
Kristie, Thomas M.
Moss, Bernard
Earl, Patricia L.
TI Susceptibility of the wild-derived inbred CAST/Ei mouse to infection by
orthopoxviruses analyzed by live bioluminescence imaging
SO VIROLOGY
LA English
DT Article
DE Poxvirus pathogenesis; Vaccinia virus pathogenesis; Cowpox virus
pathogenesis; Wild-derived inbred mice
ID MONKEYPOX VIRUS-INFECTION; VACCINIA VIRUS; GAMMA-INTERFERON; IN-VIVO;
FLAVIVIRUS RESISTANCE; CELL ENTRY; MICE; STRAINS; CIDOFOVIR; GENE
AB Classical inbred mice are extensively used for virus research. However, we recently found that some wild-derived inbred mouse strains are more susceptible than classical strains to monkeypox virus. Experiments described here indicated that the 50% lethal dose of vaccinia virus (VACV) and cowpox virus (CPXV) were two logs lower in wild-derived inbred CAST/Ei mice than classical inbred BALB/c mice, whereas there was little difference in the susceptibility of the mouse strains to herpes simplex virus. Live bioluminescence imaging was used to follow spread of pathogenic and attenuated VACV strains and CPXV virus from nasal passages to organs in the chest and abdomen of CAST/Ei mice. Luminescence increased first in the head and then simultaneously in the chest and abdomen in a dose-dependent manner. The spreading kinetics was more rapid with VACV than CPXV although the peak photon flux was similar. These data suggest advantages of CAST/Ei mice for orthopoxvirus studies. Published by Elsevier Inc.
C1 [Americo, Jeffrey L.; Sood, Cindy L.; Cotter, Catherine A.; Vogel, Jodi L.; Kristie, Thomas M.; Moss, Bernard; Earl, Patricia L.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Moss, B (reprint author), 33 North Dr, Bethesda, MD 20814 USA.
EM bmoss@nih.gov; pearl@nih.gov
FU Division of Intramural Research; NIAID; NIH
FX We thank Gary Luker for helpful discussions on bioluminescence imaging.
The research was supported by the Division of Intramural Research,
NIAID, NIH.
NR 35
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U1 0
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD JAN 20
PY 2014
VL 449
BP 120
EP 132
DI 10.1016/j.virol.2013.11.017
PG 13
WC Virology
SC Virology
GA 295CL
UT WOS:000330094100014
PM 24418545
ER
PT J
AU Deshmukh, L
Ghirlando, R
Clore, GM
AF Deshmukh, Lalit
Ghirlando, Rodolfo
Clore, G. Marius
TI Investigation of the Structure and Dynamics of the Capsid-Spacer Peptide
1-Nucleocapsid Fragment of the HIV-1 Gag Polyprotein by Solution NMR
Spectroscopy
SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
LA English
DT Article
DE nucleic acids; molecular dynamics; proteins; residual dipolar couplings;
viruses
ID TYPE-1 GAG; CHEMICAL-SHIFTS; CLEAVAGE SITES; P2 DOMAIN; RECOGNITION;
VIRIONS; STATES
AB Structural studies of HIV-1 Gag, the primary structural polyprotein involved in retroviral assembly, have been challenging, owing to its flexibility and conformational heterogeneity. Using residual dipolar couplings, we show that the four structural units of the capsid (CA)-spacer peptide1 (SP1)-nucleocapsid (NC) fragment of HIV-1 Gag (namely, the N- and C-terminal domains of capsid, and the N- and C-terminal Znknuckles of nucleocapsid) have the same structures as their individually isolated counterparts, and tumble semi-independently of one another in the absence of nucleic acids. Nucleic acids bind exclusively to the nucleocapsid domain and fix the orientation of the two Znknuckles relative to one another so that the nucleocapsid domain/nucleic acid complex behaves as a single structural unit. The low N-15-{H-1} heteronuclear NOE values (0.4), the close to zero values for the residual dipolar couplings of the backbone amides, and minimal deviations from random-coil chemical shifts for the C-terminal tail of capsid and SP1, both in the absence and presence of nucleic acids, indicate that these regions are intrinsically disordered in the context of CA-SP1-NC.
C1 [Deshmukh, Lalit; Ghirlando, Rodolfo; Clore, G. Marius] NIDDK, Labs Chem Phys & Mol Biol, NIH, Bethesda, MD 20892 USA.
RP Clore, GM (reprint author), NIDDK, Labs Chem Phys & Mol Biol, NIH, Bethesda, MD 20892 USA.
EM mariusc@mail.nih.gov
RI Clore, G. Marius/A-3511-2008; Deshmukh, Lalit/C-5073-2015
OI Clore, G. Marius/0000-0003-3809-1027;
FU NIH; NIDDK; Intramural AIDS Targeted Antiviral Program of the Office of
the Director of the NIH
FX We thank Drs. Schwieters, Grishaev, Bayro, Jenkins, and Cai for useful
discussions, Dr. Sundquist for the gift of CA-SP1-NC cDNA, and Drs.
Baber, Garrett, and Gustchina for technical support. This work was
supported by funds from the Intramural Program of the NIH, NIDDK, and
from the Intramural AIDS Targeted Antiviral Program of the Office of the
Director of the NIH (to G.M.C.).
NR 25
TC 8
Z9 8
U1 2
U2 20
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY
SN 1433-7851
EI 1521-3773
J9 ANGEW CHEM INT EDIT
JI Angew. Chem.-Int. Edit.
PD JAN 20
PY 2014
VL 53
IS 4
BP 1025
EP 1028
DI 10.1002/anie.201309127
PG 4
WC Chemistry, Multidisciplinary
SC Chemistry
GA 292CL
UT WOS:000329879500019
PM 24338988
ER
PT J
AU Margolin, G
Khil, PP
Kim, J
Bellani, MA
Camerini-Otero, RD
AF Margolin, Gennady
Khil, Pavel P.
Kim, Joongbaek
Bellani, Marina A.
Camerini-Otero, R. Daniel
TI Integrated transcriptome analysis of mouse spermatogenesis
SO BMC GENOMICS
LA English
DT Article
DE Spermatogenesis; Meiosis; RNA-Seq; Transcriptome; Deconvolution; RNA Pol
II; piRNA
ID SEX-CHROMOSOME INACTIVATION; GENOME-WIDE ANALYSIS; GENE-EXPRESSION;
MICROARRAY DATA; CHIP-SEQ; RECOMBINATION HOTSPOTS; MEIOTIC PROPHASE;
CELL-POPULATIONS; X-CHROMOSOME; RNA-SEQ
AB Background: Differentiation of primordial germ cells into mature spermatozoa proceeds through multiple stages, one of the most important of which is meiosis. Meiotic recombination is in turn a key part of meiosis. To achieve the highly specialized and diverse functions necessary for the successful completion of meiosis and the generation of spermatozoa thousands of genes are coordinately regulated through spermatogenesis. A complete and unbiased characterization of the transcriptome dynamics of spermatogenesis is, however, still lacking.
Results: In order to characterize gene expression during spermatogenesis we sequenced eight mRNA samples from testes of juvenile mice from 6 to 38 days post partum. Using gene expression clustering we defined over 1,000 novel meiotically-expressed genes. We also developed a computational de-convolution approach and used it to estimate cell type-specific gene expression in pre-meiotic, meiotic and post-meiotic cells. In addition, we detected 13,000 novel alternative splicing events around 40% of which preserve an open reading frame, and found experimental support for 159 computational gene predictions. A comparison of RNA polymerase II (Pol II) ChIP-Seq signals with RNA-Seq coverage shows that gene expression correlates well with Pol II signals, both at promoters and along the gene body. However, we observe numerous instances of non-canonical promoter usage, as well as intergenic Pol II peaks that potentially delineate unannotated promoters, enhancers or small RNA clusters.
Conclusions: Here we provide a comprehensive analysis of gene expression throughout mouse meiosis and spermatogenesis. Importantly, we find over a thousand of novel meiotic genes and over 5,000 novel potentially coding isoforms. These data should be a valuable resource for future studies of meiosis and spermatogenesis in mammals.
C1 [Margolin, Gennady; Khil, Pavel P.; Kim, Joongbaek; Camerini-Otero, R. Daniel] NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA.
[Bellani, Marina A.] NIA, NIH, Baltimore, MD 21224 USA.
RP Camerini-Otero, RD (reprint author), NIDDK, Genet & Biochem Branch, NIH, Bldg 5,Room 205A, Bethesda, MD 20892 USA.
EM rdcamerini@mail.nih.gov
FU NIDDK Intramural Research Program
FX We thank S. Sharmeen and H. Smith for assistance with high-throughput
sequencing and K. Brick, F. Pratto, K. Boateng and I. Gregoretti (all
from the Genetics and Biochemistry Branch in NIDDK) for advice and
discussions throughout this study. This work was supported by the NIDDK
Intramural Research Program (to R.D.C.-O.).
NR 64
TC 29
Z9 29
U1 2
U2 21
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 JAN 18
PY 2014
VL 15
AR 39
DI 10.1186/1471-2164-15-39
PG 19
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA AA4VZ
UT WOS:000331096000001
PM 24438502
ER
PT J
AU Feigin, VL
Forouzanfar, MH
Krishnamurthi, R
Mensah, GA
Connor, M
Bennett, DA
Moran, AE
Sacco, RL
Anderson, L
Truelsen, T
O'Donnell, M
Venketasubramanian, N
Barker-Collo, S
Lawes, CMM
Wang, WZ
Shinohara, Y
Witt, E
Ezzati, M
Naghavi, M
Murray, C
AF Feigin, Valery L.
Forouzanfar, Mohammad H.
Krishnamurthi, Rita
Mensah, George A.
Connor, Myles
Bennett, Derrick A.
Moran, Andrew E.
Sacco, Ralph L.
Anderson, Laurie
Truelsen, Thomas
O'Donnell, Martin
Venketasubramanian, Narayanaswamy
Barker-Collo, Suzanne
Lawes, Carlene M. M.
Wang, Wenzhi
Shinohara, Yukito
Witt, Emma
Ezzati, Majid
Naghavi, Mohsen
Murray, Christopher
CA Global Burden Dis Injuries Risk Fa
GBD Stroke Experts Grp
TI Global and regional burden of stroke during 1990-2010: findings from the
Global Burden of Disease Study 2010
SO LANCET
LA English
DT Article
ID SYSTEMATIC ANALYSIS; CASE-FATALITY; ISCHEMIC-STROKE; MONICA PROJECT;
HEART-DISEASE; 187 COUNTRIES; YOUNG-ADULTS; RISK-FACTORS; MORTALITY;
TRENDS
AB Background Although stroke is the second leading cause of death worldwide, no comprehensive and comparable assessment of incidence, prevalence, mortality, disability, and epidemiological trends has been estimated for most regions. We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010) to estimate the global and regional burden of stroke during 1990-2010.
Methods We searched Medline, Embase, LILACS, Scopus, PubMed, Science Direct, Global Health Database, the WHO library, and WHO regional databases from 1990 to 2012 to identify relevant studies published between 1990 and 2010. We applied the GBD 2010 analytical technique (DisMod-MR), based on disease-specific, pre-specified associations between incidence, prevalence, and mortality, to calculate regional and country-specific estimates of stroke incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) lost by age group (<75 years, >= 75 years, and in total) and country income level (high-income, and low-income and middle-income) for 1990, 2005, and 2010.
Findings We included 119 studies (58 from high-income countries and 61 from low-income and middle-income countries). From 1990 to 2010, the age-standardised incidence of stroke significantly decreased by 12% (95% CI 6-17) in high-income countries, and increased by 12% (-3 to 22) in low-income and middle-income countries, albeit nonsignificantly. Mortality rates decreased significantly in both high income (37%, 31-41) and low-income and middle-income countries (20%, 15-30). In 2010, the absolute numbers of people with first stroke (16.9 million), stroke survivors (33 million), stroke-related deaths (5.9 million), and DALYs lost (102 million) were high and had significantly increased since 1990 (68%, 84%, 26%, and 12% increase, respectively), with most of the burden (68.6% incident strokes, 52.2% prevalent strokes, 70.9% stroke deaths, and 77.7% DALYs lost) in low-income and middle-income countries. In 2010, 5.2 million (31%) strokes were in children (aged <20 years old) and young and middle-aged adults (20-64 years), to which children and young and middle-aged adults from low-income and middle-income countries contributed almost 74 000 (89%) and 4.0 million (78%), respectively, of the burden. Additionally, we noted significant geographical differences of between three and ten times in stroke burden between GBD regions and countries. More than 62% of new strokes, 69.8% of prevalent strokes, 45.5% of deaths from stroke, and 71.7% of DALYs lost because of stroke were in people younger than 75 years.
Interpretation Although age-standardised rates of stroke mortality have decreased worldwide in the past two decades, the absolute number of people who have a stroke every year, stroke survivors, related deaths, and the overall global burden of stroke (DALYs lost) are great and increasing. Further study is needed to improve understanding of stroke determinants and burden worldwide, and to establish causes of disparities and changes in trends in stroke burden between countries of different income levels.
C1 [Feigin, Valery L.; Krishnamurthi, Rita; Witt, Emma] Auckland Uwnivers Technol, Fac Hlth & Environm Studies, Natl Inst Stroke & Appl Neurosci, Auckland, New Zealand.
[Forouzanfar, Mohammad H.; Naghavi, Mohsen; Murray, Christopher] Univ Washington, Dept Global Hlth, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
[Mensah, George A.] NIH, Heart Lung & Blood Inst, Bethesda, MD 20892 USA.
[Connor, Myles] Univ Edinburgh, Div Clin Neurosci, Edinburgh EH8 9YL, Midlothian, Scotland.
[Connor, Myles] Univ St Andrews, Bute Med Sch, St Andrews KY16 9AJ, Fife, Scotland.
[Connor, Myles] Univ Witwatersrand, Sch Publ Hlth, ZA-2050 Johannesburg, South Africa.
[Bennett, Derrick A.] Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford, England.
[Bennett, Derrick A.] Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit, Oxford, England.
[Moran, Andrew E.] Columbia Univ, Med Ctr, Div Gen Med, New York, NY 10027 USA.
[Sacco, Ralph L.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
[Anderson, Laurie] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
[Anderson, Laurie] Washington State Inst Publ Policy, Olympia, WA USA.
[Truelsen, Thomas] Univ Copenhagen, Herlev Hosp, Dept Neurol, DK-2730 Herlev, Denmark.
[Ezzati, Majid] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, MRC HPA Ctr Environm & Hlth, London, England.
[O'Donnell, Martin] Natl Univ Ireland, Galway, Ireland.
[Venketasubramanian, Narayanaswamy] Natl Univ Singapore, Yong Loo Lin Sch Med, Univ Med Cluster, Div Neurol, Singapore 117548, Singapore.
[Venketasubramanian, Narayanaswamy] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore.
[Barker-Collo, Suzanne] Univ Auckland, Sch Psychol, Auckland 1, New Zealand.
[Lawes, Carlene M. M.] Univ Auckland, Natl Inst Hlth Innovat, Auckland 1, New Zealand.
[Wang, Wenzhi] Capital Med Univ, Beijing Neurosurg Inst, Beijing, Peoples R China.
[Shinohara, Yukito] Federat Natl Publ Serv Personnel Mutual Aid Assoc, Tachikawa, Tokyo, Japan.
RP Feigin, VL (reprint author), Auckland Univ Technol Univ, Fac Hlth & Environm Studies, Sch Publ Hlth & Psychosocial Studies, Natl Inst Stroke & Appl Neurosci,Sch Rehabil & Oc, Auckland 1142, New Zealand.
EM valery.feigin@aut.ac.nz
OI O'Donnell, Martin/0000-0002-7347-7761
FU Bill & Melinda Gates Foundation
FX Bill & Melinda Gates Foundation.
NR 50
TC 556
Z9 584
U1 26
U2 116
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 JAN 18
PY 2014
VL 383
IS 9913
BP 245
EP 255
DI 10.1016/S0140-6736(13)61953-4
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 294FC
UT WOS:000330027500033
PM 24449944
ER
PT J
AU Rais-Bahrami, S
Turkbey, B
Grant, KB
Pinto, PA
Choyke, PL
AF Rais-Bahrami, Soroush
Turkbey, Baris
Grant, Kinzya B.
Pinto, Peter A.
Choyke, Peter L.
TI Role of Multiparametric Magnetic Resonance Imaging in the Diagnosis of
Prostate Cancer
SO CURRENT UROLOGY REPORTS
LA English
DT Article
DE Cancer Detection; Magnetic Resonance Imaging; Prostate Biopsy; Cancer
Imaging
ID TRANSRECTAL ULTRASOUND BIOPSY; RADICAL PROSTATECTOMY; FUSION BIOPSY;
ACTIVE SURVEILLANCE; TARGETED BIOPSIES; 3-T MRI; 3 TESLA; EXTENSION;
MORTALITY; SPECIMENS
AB Prostate cancer is the most common solid-organ malignancy among American men. It is currently most commonly diagnosed on random systematic biopsies prompted by elevated serum PSA levels. Multi-parametric MRI (MP-MRI) of the prostate has emerged as an anatomic and functional imaging modality, which offers accurate detection, localization and staging of prostate cancer. Recently, MP-MRI has gained an increasing role in guiding biopsies to sites of abnormality and in monitoring patients on active surveillance. Here, we discuss the historical development, current role, and potential future directions of MP-MRI in the diagnosis of prostate cancer.
C1 [Rais-Bahrami, Soroush; Pinto, Peter A.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Turkbey, Baris; Grant, Kinzya B.; 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 Turkbey, B (reprint author), NCI, Mol Imaging Program, NIH, 10 Ctr Dr,Bldg 10-CRC, Bethesda, MD 20892 USA.
EM turkbeyi@mail.nih.gov
OI Rais-Bahrami, Soroush/0000-0001-9466-9925
FU Intramural Research Program of the National Institutes of Health; Center
for Interventional Oncology; National Cancer Institute; Center for
Cancer Research
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research, and the Center for Interventional Oncology. NIH and
Philips Healthcare have a cooperative research and development
agreement. NIH and Philips share intellectual property in the field.
NR 52
TC 8
Z9 8
U1 1
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1527-2737
J9 CURR UROL REP
JI Curr. Urol. Rep.
PD JAN 17
PY 2014
VL 15
IS 3
AR 387
DI 10.1007/s11934-013-0387-9
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA AJ7UB
UT WOS:000337902400001
PM 24430169
ER
PT J
AU Ramadoss, P
Abraham, BJ
Tsai, L
Zhou, YM
Costa-e-Sousa, RH
Ye, FL
Bilban, M
Zhao, KJ
Hollenberg, AN
AF Ramadoss, Preeti
Abraham, Brian J.
Tsai, Linus
Zhou, Yiming
Costa-e-Sousa, Ricardo H.
Ye, Felix
Bilban, Martin
Zhao, Keji
Hollenberg, Anthony N.
TI Novel Mechanism of Positive versus Negative Regulation by Thyroid
Hormone Receptor beta 1 (TR beta 1) Identified by Genome-wide Profiling
of Binding Sites in Mouse Liver
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Chromatin Immunoprecipitation (ChIP); Nuclear Receptors; Thyroid
Hormone; Transcription Regulation; Transcription Target Genes; ChIP-seq;
TRb1; Thyroid Hormone Receptor; gpd2; thrsp
ID RETINOID-X-RECEPTOR; IN-VIVO; GENE-EXPRESSION; RESPONSE ELEMENTS;
NUCLEAR RECEPTOR; TRANSCRIPTION FACTOR; DNA-SEQUENCES; KNOCKOUT MICE;
ACID RECEPTOR; CO-REPRESSOR
AB Background: Examining the TR1 cistrome in mouse liver is critical to understanding thyroid hormone signaling. Results: Novel mechanisms of positive versus negative regulation by biotinylated TR1 were identified. Conclusion: TR1 regulates transcription by changes in relative binding and use of preferred binding motifs. Significance: This study demonstrates that a mechanism other than differential co-regulator recruitment is involved in transcriptional regulation by TR1
Triiodothyronine (T3) regulates key metabolic processes in the liver through the thyroid hormone receptor, TR1. However, the number of known target genes directly regulated by TR1 is limited, and the mechanisms by which positive and especially negative transcriptional regulation occur are not well understood. To characterize the TR1 cistrome in vivo, we expressed a biotinylated TR1 in hypo- and hyperthyroid mouse livers, used ChIP-seq to identify genomic TR1 targets, and correlated these data with gene expression changes. As with other nuclear receptors, the majority of TR1 binding sites were not in proximal promoters but in the gene body of known genes. Remarkably, T3 can dictate changes in TR1 binding, with strong correlation to T3-induced gene expression changes, suggesting that differential TR1 binding regulates transcriptional outcome. Additionally, DR-4 and DR-0 motifs were significantly enriched at binding sites where T3 induced an increase or decrease in TR1 binding, respectively, leading to either positive or negative regulation by T3. Taken together, the results of this study provide new insights into the mechanisms of transcriptional regulation by TR1 in vivo.
C1 [Ramadoss, Preeti; Tsai, Linus; Zhou, Yiming; Costa-e-Sousa, Ricardo H.; Ye, Felix; Hollenberg, Anthony N.] Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02115 USA.
[Abraham, Brian J.; Zhao, Keji] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA.
[Bilban, Martin] Med Univ Vienna, Dept Lab Med, A-1090 Vienna, Austria.
[Bilban, Martin] Med Univ Vienna, Core Facil, Core Facil Genom, A-1090 Vienna, Austria.
RP Hollenberg, AN (reprint author), Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, 330 Brookline Ave, Boston, MA 02115 USA.
EM thollenb@bidmc.harvard.edu
OI Tsai, Linus/0000-0002-0134-6949
FU National Institutes of Health [DK-091941, DK-056123]
FX This work was supported, in whole or in part, by National Institutes of
Health Grants DK-091941 and DK-056123 (to A. N. H.).
NR 57
TC 22
Z9 22
U1 1
U2 8
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JAN 17
PY 2014
VL 289
IS 3
BP 1313
EP 1328
DI 10.1074/jbc.M113.521450
PG 16
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AC3FS
UT WOS:000332401700011
PM 24288132
ER
PT J
AU Zhou, FJ
Walker, SE
Mitchell, SF
Lorsch, JR
Hinnebusch, AG
AF Zhou, Fujun
Walker, Sarah E.
Mitchell, Sarah F.
Lorsch, Jon R.
Hinnebusch, Alan G.
TI Identification and Characterization of Functionally Critical, Conserved
Motifs in the Internal Repeats and N-terminal Domain of Yeast
Translation Initiation Factor 4B (yeIF4B)
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE mRNA; Ribosomes; Translation Initiation Factors; Translation Regulation;
Yeast; eIF4A; eIF4B; Translation Initiation; Yeast Translation
ID RNA RECOGNITION MOTIF; SACCHAROMYCES-CEREVISIAE; MESSENGER-RNA; HELICASE
ACTIVITY; SHUTTLE VECTORS; IN-VIVO; EIF4B; COMPLEX; PROTEIN; SELECTION
AB Background: The internal repeats and NTD of yeIF4B stimulate translation initiation. Results: The minimal number of repeats and conserved motifs in the repeat and NTD necessary for yeIF4B function was determined. Conclusion: Two repeats provide appreciable function, except when the NTD is missing or eIF4F function is limiting or compromised. Significance: The results provide a comprehensive description of functionally critical sequence elements in yeIF4B.
eIF4B has been implicated in attachment of the 43 S preinitiation complex (PIC) to mRNAs and scanning to the start codon. We recently determined that the internal seven repeats (of approximate to 26 amino acids each) of Saccharomyces cerevisiae eIF4B (yeIF4B) compose the region most critically required to enhance mRNA recruitment by 43 S PICs in vitro and stimulate general translation initiation in yeast. Moreover, although the N-terminal domain (NTD) of yeIF4B contributes to these activities, the RNA recognition motif is dispensable. We have now determined that only two of the seven internal repeats are sufficient for wild-type (WT) yeIF4B function in vivo when all other domains are intact. However, three or more repeats are needed in the absence of the NTD or when the functions of eIF4F components are compromised. We corroborated these observations in the reconstituted system by demonstrating that yeIF4B variants with only one or two repeats display substantial activity in promoting mRNA recruitment by the PIC, whereas additional repeats are required at lower levels of eIF4A or when the NTD is missing. These findings indicate functional overlap among the 7-repeats and NTD domains of yeIF4B and eIF4A in mRNA recruitment. Interestingly, only three highly conserved positions in the 26-amino acid repeat are essential for function in vitro and in vivo. Finally, we identified conserved motifs in the NTD and demonstrate functional overlap of two such motifs. These results provide a comprehensive description of the critical sequence elements in yeIF4B that support eIF4F function in mRNA recruitment by the PIC.
C1 [Zhou, Fujun; Hinnebusch, Alan G.] Eunice Kennedy Shriver NICHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA.
[Walker, Sarah E.; Mitchell, Sarah F.; Lorsch, Jon R.] Johns Hopkins Univ, Dept Biophys & Biophys Chem, Sch Med, Baltimore, MD 21205 USA.
RP Lorsch, JR (reprint author), Eunice Kennedy Shriver NICHD, Lab Mech & Regulat Prot Synth, NIH, Bldg 45,Rm 3AN44, Bethesda, MD 20892 USA.
EM jon.lorsch@nih.gov; ahinnebusch@nih.gov
OI Lorsch, Jon/0000-0002-4521-4999; Walker, Sarah/0000-0002-9983-2485
FU National Institutes of Health; American Heart Association; [GM62128]
FX This work was supported, in whole or in part, by National Institutes of
Health Intramural Research Program Grant (to A. G. H. and F. Z.) and
Grant GM62128 (to J. R. L.). This work was also supported by an American
Heart Association postdoctoral fellowship (to S. E. W.).
NR 37
TC 6
Z9 6
U1 0
U2 0
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JAN 17
PY 2014
VL 289
IS 3
BP 1704
EP 1722
DI 10.1074/jbc.M113.529370
PG 19
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AC3FS
UT WOS:000332401700042
PM 24285537
ER
PT J
AU Antony, ML
Lee, J
Hahm, ER
Kim, SH
Marcus, AI
Kumari, V
Ji, XH
Yang, Z
Vowell, CL
Wipf, P
Uechi, GT
Yates, NA
Romero, G
Sarkar, SN
Singh, SV
AF Antony, Marie L.
Lee, Joomin
Hahm, Eun-Ryeong
Kim, Su-Hyeong
Marcus, Adam I.
Kumari, Vandana
Ji, Xinhua
Yang, Zhen
Vowell, Courtney L.
Wipf, Peter
Uechi, Guy T.
Yates, Nathan A.
Romero, Guillermo
Sarkar, Saumendra N.
Singh, Shivendra V.
TI Growth Arrest by the Antitumor Steroidal Lactone Withaferin A in Human
Breast Cancer Cells Is Associated with Down-regulation and Covalent
Binding at Cysteine 303 of beta-Tubulin
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Breast Cancer; Cancer Chemoprevention; Cell Cycle; Natural Products;
Tubulin; Withaferin A
ID WITHANIA-SOMNIFERA; ALLYL ISOTHIOCYANATE; COMPOUND WITHAFERIN; AYURVEDIC
MEDICINE; MICHAEL ACCEPTORS; INDUCED APOPTOSIS; GENE-EXPRESSION; MITOTIC
ARREST; IN-VIVO; AGENTS
AB Background: The tubulin microtubule network remains an attractive anticancer target. Results: The antitumor steroidal lactone withaferin A (WA) down-regulates tubulin and binds to Cys(303) of -tubulin. Conclusion: Tubulin is a novel target of WA-mediated growth arrest in human breast cancer cells. Significance: Favorable safety and pharmacokinetic profiles merit clinical investigation of WA for prevention and/or treatment of breast cancer.
Withaferin A (WA), a C-5,C-6-epoxy steroidal lactone derived from a medicinal plant (Withania somnifera), inhibits growth of human breast cancer cells in vitro and in vivo and prevents mammary cancer development in a transgenic mouse model. However, the mechanisms underlying the anticancer effect of WA are not fully understood. Herein, we report that tubulin is a novel target of WA-mediated growth arrest in human breast cancer cells. The G(2) and mitotic arrest resulting from WA exposure in MCF-7, SUM159, and SK-BR-3 cells was associated with a marked decrease in protein levels of -tubulin. These effects were not observed with the naturally occurring C-6,C-7-epoxy analogs of WA (withanone and withanolide A). A non-tumorigenic normal mammary epithelial cell line (MCF-10A) was markedly more resistant to mitotic arrest by WA compared with breast cancer cells. Vehicle-treated control cells exhibited a normal bipolar spindle with chromosomes aligned along the metaphase plate. In contrast, WA treatment led to a severe disruption of normal spindle morphology. NMR analyses revealed that the A-ring enone in WA, but not in withanone or withanolide A, was highly reactive with cysteamine and rapidly succumbed to irreversible nucleophilic addition. Mass spectrometry demonstrated direct covalent binding of WA to Cys(303) of -tubulin in MCF-7 cells. Molecular docking indicated that the WA-binding pocket is located on the surface of -tubulin and characterized by a hydrophobic floor, a hydrophobic wall, and a charge-balanced hydrophilic entrance. These results provide novel insights into the mechanism of growth arrest by WA in breast cancer cells.
C1 [Antony, Marie L.; Lee, Joomin; Hahm, Eun-Ryeong; Kim, Su-Hyeong; Romero, Guillermo; Singh, Shivendra V.] Univ Pittsburgh, Dept Pharmacol & Chem Biol, Sch Med, Pittsburgh, PA 15260 USA.
[Sarkar, Saumendra N.] Univ Pittsburgh, Dept Microbiol & Mol Genet, Sch Med, Pittsburgh, PA 15260 USA.
[Vowell, Courtney L.; Wipf, Peter] Univ Pittsburgh, Dept Chem, Pittsburgh, PA 15260 USA.
[Marcus, Adam I.; Yang, Zhen] Emory Univ, Dept Hematol & Med Oncol, Atlanta, GA 30322 USA.
[Kumari, Vandana; Ji, Xinhua] NCI, Biomol Struct Sect, Ctr Canc Res, Frederick, MD 21702 USA.
[Uechi, Guy T.; Yates, Nathan A.] Univ Pittsburgh, Sch Med, Biomed Mass Spectrometry Ctr, Pittsburgh, PA 15213 USA.
[Uechi, Guy T.; Yates, Nathan A.; Sarkar, Saumendra N.; Singh, Shivendra V.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15213 USA.
RP Singh, SV (reprint author), Univ Pittsburgh, Hillman Canc Ctr 2 32A, Inst Canc, 5117 Ctr Ave, Pittsburgh, PA 15213 USA.
EM singhs@upmc.edu
RI Sarkar, Saumendra/B-5038-2011
OI Sarkar, Saumendra/0000-0002-2850-6121
FU National Institutes of Health from NCI [R01 CA142604-04, R01
CA129347-07]; Center for Cancer Research, NCI, National Institutes of
Health; National Institutes of Health Cancer Center from NCI
[P30CA047904]
FX This work was supported, in whole or in part, by National Institutes of
Health Grants R01 CA142604-04 and R01 CA129347-07 from NCI (to S. V. S.)
and by the Intramural Research Program of the Center for Cancer
Research, NCI, National Institutes of Health (to X. J.). The work
performed in the University of Pittsburgh Cancer Institute Flow
Cytometry Facility and Cancer Biomarkers Facility was supported in part
by National Institutes of Health Cancer Center Support Grant P30CA047904
from NCI.
NR 50
TC 24
Z9 24
U1 0
U2 12
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JAN 17
PY 2014
VL 289
IS 3
BP 1852
EP 1865
DI 10.1074/jbc.M113.496844
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AC3FS
UT WOS:000332401700054
PM 24297176
ER
PT J
AU Ravussin, Y
Xiao, CY
Gavrilova, O
Reitman, ML
AF Ravussin, Yann
Xiao, Cuiying
Gavrilova, Oksana
Reitman, Marc L.
TI Effect of Intermittent Cold Exposure on Brown Fat Activation, Obesity,
and Energy Homeostasis in Mice
SO PLOS ONE
LA English
DT Article
ID UNCOUPLING PROTEIN GENE; WHITE ADIPOSE-TISSUE; INSULIN SENSITIVITY;
C57BL/6J MICE; PLASMA LEPTIN; THERMOGENESIS; EXPRESSION; RATS; DIET;
EXPENDITURE
AB Homeotherms have specific mechanisms to maintain a constant core body temperature despite changes in thermal environment, food supply, and metabolic demand. Brown adipose tissue, the principal thermogenic organ, quickly and efficiently increases heat production by dissipating the mitochondrial proton motive force. It has been suggested that activation of brown fat, via either environmental (i.e. cold exposure) or pharmacologic means, could be used to increase metabolic rate and thus reduce body weight. Here we assess the effects of intermittent cold exposure (4 degrees C for one to eight hours three times a week) on C57BL/6J mice fed a high fat diet. Cold exposure increased metabolic rate approximately twofold during the challenge and activated brown fat. In response, food intake increased to compensate fully for the increased energy expenditure; thus, the mice showed no reduction in body weight or adiposity. Despite the unchanged adiposity, the cold-treated mice showed transient improvements in glucose homeostasis. Administration of the cannabinoid receptor-1 inverse agonist AM251 caused weight loss and improvements in glucose homeostasis, but showed no further improvements when combined with cold exposure. These data suggest that intermittent cold exposure causes transient, meaningful improvements in glucose homeostasis, but without synergy when combined with AM251. Since energy expenditure is significantly increased during cold exposure, a drug that dissociates food intake from metabolic demand during cold exposure may achieve weight loss and further metabolic improvements.
C1 [Ravussin, Yann; Xiao, Cuiying; Reitman, Marc L.] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA.
[Gavrilova, Oksana] NIDDK, Mouse Metab Core, NIH, Bethesda, MD 20892 USA.
RP Reitman, ML (reprint author), NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA.
EM marc.reitman@nih.gov
RI Reitman, Marc/B-4448-2013
OI Reitman, Marc/0000-0002-0426-9475
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK), NIH [ZIA DK075062, ZIA DK075064,
ZIA DK070002]; Swiss National Fund for Scientific Research (SNF)
FX This research was supported by the Intramural Research Program (ZIA
DK075062, ZIA DK075064, ZIA DK070002) of the National Institute of
Diabetes and Digestive and Kidney Diseases (NIDDK), NIH. YR was
supported by a grant from the Swiss National Fund for Scientific
Research (SNF). The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 45
TC 21
Z9 23
U1 0
U2 13
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 JAN 17
PY 2014
VL 9
IS 1
AR e85876
DI 10.1371/journal.pone.0085876
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 297EA
UT WOS:000330237000069
PM 24465761
ER
PT J
AU Selvaraj, S
Borkar, DS
Prasad, V
AF Selvaraj, Senthil
Borkar, Durga S.
Prasad, Vinay
TI Media Coverage of Medical Journals: Do the Best Articles Make the News?
SO PLOS ONE
LA English
DT Article
ID PRESS RELEASES; TRIALS; CANCER
AB Background: News coverage of medical research is followed closely by many Americans and affects the practice of medicine and influence of scientific research. Prior work has examined the quality of media coverage, but no investigation has characterized the choice of stories covered in a controlled manner. We examined whether the media systematically covers stories of weaker study design.
Methods: We compared study characteristics of 75 clinically-oriented journal articles that received coverage in the top five newspapers by circulation against 75 clinically-oriented journal articles that appeared in the top five medical journals by impact factor over a similar timespan. Subgroup analysis was performed to determine whether differences between investigations from both sources varied by study type (randomized controlled trial [RCT] or observational study).
Results: Investigations receiving coverage from newspapers were less likely to be RCTs (17% vs. 35%, p < 0.016) and more likely to be observational studies (75% vs. 47%, p < 0.001). No difference was observed in number of people studied (median: 1034 vs. 1901, p = 0.14) or length of follow-up (median: 1.80 vs. 1.00 years, p = 0.22). In subgroup analysis, observational studies from the media used smaller sample sizes (median: 1984 vs. 21136, p = 0.029) and were more likely to be cross-sectional (71% vs. 31%, p < 0.001), while no differences were observed for RCTs.
Conclusions: Newspapers were more likely to cover observational studies and less likely to cover RCTs than high impact journals. Additionally, when the media does cover observational studies, they select articles of inferior quality. Newspapers preferentially cover medical research with weaker methodology.
C1 [Selvaraj, Senthil] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Borkar, Durga S.] Beth Israel Deaconess Brockton, Dept Med, Brockton, MA USA.
[Prasad, Vinay] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Prasad, V (reprint author), NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
EM vinayak.prasad@nih.gov
NR 30
TC 5
Z9 5
U1 1
U2 10
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JAN 17
PY 2014
VL 9
IS 1
AR e85355
DI 10.1371/journal.pone.0085355
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 297EA
UT WOS:000330237000031
PM 24465543
ER
PT J
AU Almaidhan, A
Cesario, J
Malt, AL
Zhao, YG
Sharma, N
Choi, V
Jeong, JH
AF Almaidhan, Asma
Cesario, Jeffry
Malt, Andre Landin
Zhao, Yangu
Sharma, Neeti
Choi, Veronica
Jeong, Juhee
TI Neural crest-specific deletion of Ldb1 leads to cleft secondary palate
with impaired palatal shelf elevation
SO BMC DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE Cleft palate; Craniofacial development; LDB1
ID LIM-HOMEODOMAIN PROTEINS; MUTANT MICE; MOLECULAR-MECHANISMS;
CELL-PROLIFERATION; GROWTH; PALATOGENESIS; MORPHOGENESIS; MESENCHYME;
DIFFERENTIATION; REQUIREMENT
AB Background: LIM domain binding protein 1 (LDB1) is a transcriptional co-factor, which interacts with multiple transcription factors and other proteins containing LIM domains. Complete inactivation of Ldb1 in mice resulted in early embryonic lethality with severe patterning defects during gastrulation. Tissue-specific deletions using a conditional knockout allele revealed additional roles of Ldb1 in the development of the central nervous system, hematopoietic system, and limbs. The goal of the current study was to determine the importance of Ldb1 function during craniofacial development in mouse embryos.
Results: We generated tissue-specific Ldb1 mutants using Wnt1-Cre, which causes deletion of a floxed allele in the neural crest; neural crest-derived cells contribute to most of the mesenchyme of the developing face. All examined Wnt1-Cre; Ldb1(fl/-) mutants suffered from cleft secondary palate. Therefore, we performed a series of experiments to investigate how Ldb1 regulated palate development. First, we examined the expression of Ldb1 during normal development, and found that Ldb1 was expressed broadly in the palatal mesenchyme during early stages of palate development. Second, we compared the morphology of the developing palate in control and Ldb1 mutant embryos using sections. We found that the mutant palatal shelves had abnormally blunt appearance, and failed to elevate above the tongue at the posterior domain. An in vitro head culture experiment indicated that the elevation defect was not due to interference by the tongue. Finally, in the Ldb1 mutant palatal shelves, cell proliferation was abnormal in the anterior, and the expression of Wnt5a, Pax9 and Osr2, which regulate palatal shelf elevation, was also altered.
Conclusions: The function of Ldb1 in the neural crest-derived palatal mesenchyme is essential for normal morphogenesis of the secondary palate.
C1 [Almaidhan, Asma; Cesario, Jeffry; Malt, Andre Landin; Sharma, Neeti; Choi, Veronica; Jeong, Juhee] NYU, Coll Dent, Dept Basic Sci & Craniofacial Biol, New York, NY 10010 USA.
[Almaidhan, Asma] NYU, Coll Dent, Consortium Translat Orthodont Res, New York, NY 10010 USA.
[Zhao, Yangu] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Program Genom Differentiat, Bethesda, MD 20892 USA.
RP Jeong, JH (reprint author), NYU, Coll Dent, Dept Basic Sci & Craniofacial Biol, New York, NY 10010 USA.
EM jj78@nyu.edu
FU NIH [NIDCR R00 DE019486]
FX This work was funded by a grant from NIH (NIDCR R00 DE019486) to J.J.
NR 45
TC 2
Z9 2
U1 0
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-213X
J9 BMC DEV BIOL
JI BMC Dev. Biol.
PD JAN 17
PY 2014
VL 14
AR 3
DI 10.1186/1471-213X-14-3
PG 10
WC Developmental Biology
SC Developmental Biology
GA 294RY
UT WOS:000330066000001
PM 24433583
ER
PT J
AU Johnston, WT
Mutalima, N
Sun, D
Emmanuel, B
Bhatia, K
Aka, P
Wu, XL
Borgstein, E
Liomba, GN
Kamiza, S
Mkandawire, N
Batumba, M
Carpenter, LM
Jaffe, H
Molyneux, EM
Goedert, JJ
Soppet, D
Newton, R
Mbulaiteye, SM
AF Johnston, W. Thomas
Mutalima, Nora
Sun, David
Emmanuel, Benjamin
Bhatia, Kishor
Aka, Peter
Wu, Xiaolin
Borgstein, E.
Liomba, G. N.
Kamiza, Steve
Mkandawire, Nyengo
Batumba, Mkume
Carpenter, Lucy M.
Jaffe, Harold
Molyneux, Elizabeth M.
Goedert, James J.
Soppet, Daniel
Newton, Robert
Mbulaiteye, Sam M.
TI Relationship between Plasmodium falciparum malaria prevalence, genetic
diversity and endemic Burkitt lymphoma in Malawi
SO SCIENTIFIC REPORTS
LA English
DT Article
ID EPSTEIN-BARR-VIRUS; B-CELL ACTIVATOR; CHILDREN; ANTIBODIES; UGANDA;
IDENTIFICATION; COMPLEXITY; INFECTION; GENOTYPES; DISEASE
AB Endemic Burkitt lymphoma (eBL) has been linked to Plasmodium falciparum (Pf) malaria infection, but the contribution of infection with multiple Pf genotypes is uncertain. We studied 303 eBL (cases) and 274 non eBL-related cancers (controls) in Malawi using a sensitive and specific molecular-barcode array of 24 independently segregating Pf single nucleotide polymorphisms. Cases had a higher Pf malaria prevalence than controls (64.7% versus 45.3%; odds ratio [OR] 2.1, 95% confidence interval (CI): 1.5 to 3.1). Cases and controls were similar in terms of Pf density (4.9 versus 4.5 log copies, p = 0.28) and having >= 3 non-clonal calls (OR 2.7, 95% CI: 0.7-9.9, P = 0.14). However, cases were more likely to have a higher Pf genetic diversity score (153.9 versus 133.1, p = 0.036), which measures a combination of clonal and non-clonal calls, than controls. Further work is needed to evaluate the possible role of Pf genetic diversity in the pathogenesis of endemic BL.
C1 [Johnston, W. Thomas; Mutalima, Nora; Newton, Robert] Univ York, York YO10 5DD, N Yorkshire, England.
[Sun, David; Wu, Xiaolin; Soppet, Daniel] Frederick Natl Lab Canc Res, Frederick, MD USA.
[Emmanuel, Benjamin; Bhatia, Kishor; Aka, Peter; Goedert, James J.; Mbulaiteye, Sam M.] Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Borgstein, E.; Liomba, G. N.; Kamiza, Steve; Mkandawire, Nyengo; Batumba, Mkume; Molyneux, Elizabeth M.] Queen Elizabeth Hosp, Blantyre, Malawi.
[Carpenter, Lucy M.; Jaffe, Harold] Univ Oxford, Oxford, England.
RP Mbulaiteye, SM (reprint author), Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
EM mbulaits@mail.nih.gov
FU National Cancer Institute's Director's Innovation Award [NO2-CP-31003]
FX The work was supported by the National Cancer Institute's Director's
Innovation Award to Dr. S.M. Mbulaiteye in the Intramural Research
Program of the Division of Cancer Epidemiology and Genetics, National
Cancer Institute at the National Institutes of Health, Department of
Health and Human Services (Support Services Contract NO2-CP-31003).
NR 31
TC 7
Z9 7
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JAN 17
PY 2014
VL 4
AR 3741
DI 10.1038/srep03741
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 291SH
UT WOS:000329849100007
PM 24434689
ER
PT J
AU Sun, W
Tanaka, TQ
Magle, CT
Huang, WW
Southall, N
Huang, RL
Dehdashti, SJ
McKew, JC
Williamson, KC
Zheng, W
AF Sun, Wei
Tanaka, Takeshi Q.
Magle, Crystal T.
Huang, Wenwei
Southall, Noel
Huang, Ruili
Dehdashti, Seameen J.
McKew, John C.
Williamson, Kim C.
Zheng, Wei
TI Chemical signatures and new drug targets for gametocytocidal drug
development
SO SCIENTIFIC REPORTS
LA English
DT Article
ID HIGH-THROUGHPUT SCREEN; PLASMODIUM-FALCIPARUM GROWTH; COMBINATION
THERAPY; MALARIA; INHIBITOR; TRANSMISSION; STAGE; ASSAY;
HEAT-SHOCK-PROTEIN-90; IDENTIFICATION
AB Control of parasite transmission is critical for the eradication of malaria. However, most antimalarial drugs are not active against P. falciparum gametocytes, responsible for the spread of malaria. Consequently, patients can remain infectious for weeks after the clearance of asexual parasites and clinical symptoms. Here we report the identification of 27 potent gametocytocidal compounds (IC50 < 1 mu M) from screening 5,215 known drugs and compounds. All these compounds were active against three strains of gametocytes with different drug sensitivities and geographical origins, 3D7, HB3 and Dd2. Cheminformatic analysis revealed chemical signatures for P. falciparum sexual and asexual stages indicative of druggability and suggesting potential targets. Torin 2, a top lead compound (IC50 = 8 nM against gametocytes in vitro), completely blocked oocyst formation in a mouse model of transmission. These results provide critical new leads and potential targets to expand the repertoire of malaria transmission-blocking reagents.
C1 [Sun, Wei; Huang, Wenwei; Southall, Noel; Huang, Ruili; Dehdashti, Seameen J.; McKew, John C.; Zheng, Wei] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
[Tanaka, Takeshi Q.; Williamson, Kim C.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
[Magle, Crystal T.; Williamson, Kim C.] Loyola Univ, Dept Biol, Chicago, IL 60660 USA.
RP Williamson, KC (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM kwilli4@luc.edu; wzheng@mail.nih.gov
RI Magle, C. Tobin/J-7889-2015; Southall, Noel/H-8991-2012; Zheng,
Wei/J-8889-2014
OI Magle, C. Tobin/0000-0003-3185-7034; Southall, Noel/0000-0003-4500-880X;
Zheng, Wei/0000-0003-1034-0757
FU Intramural Research Programs of the National Center for Advancing
Translational Sciences; National Institute of Allergy and Infectious
Diseases; Public Health Service grant from National Institute of Allergy
and Infectious Diseases [AI101396]
FX This work was supported by the Intramural Research Programs of the
National Center for Advancing Translational Sciences and National
Institute of Allergy and Infectious Diseases, and Public Health Service
grant AI101396 from the National Institute of Allergy and Infectious
Diseases. TQT is a JSPS Research Fellow in Biomedical and Behavioral
Research at the NIH. We thank Mr. Paul Shinn from the National Center
for Advancing Translational Sciences for preparing compound plates and
Ms. Sullivan from the National Institute of Allergy and Infectious
Diseases for technical assistance. We also thank Dr. Zhaojing Meng from
SAIC for mass spectrometry analysis.
NR 58
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Z9 33
U1 2
U2 18
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JAN 17
PY 2014
VL 4
AR 3743
DI 10.1038/srep03743
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 291SH
UT WOS:000329849100009
PM 24434750
ER
PT J
AU Rho, JH
Mead, JR
Wright, WS
Brenner, DE
Stave, JW
Gildersleeve, JC
Lampe, PD
AF Rho, Jung-hyun
Mead, Judson R.
Wright, W. Shea
Brenner, Dean E.
Stave, James W.
Gildersleeve, Jeffrey C.
Lampe, Paul D.
TI Discovery of sialyl Lewis A and Lewis X modified protein cancer
biomarkers using high density antibody arrays
SO JOURNAL OF PROTEOMICS
LA English
DT Article
DE Glycoproteins; Glycans; Sialyl Lewis A; Lewis X; Cancer biomarker;
Antibody array
ID LECTIN SANDWICH ARRAYS; PANCREATIC-CANCER; HIGH-THROUGHPUT;
GASTROINTESTINAL CANCER; COLORECTAL-CARCINOMA; GLYCANS; ANTIGEN;
CA-19-9; SERUM; CARRIER
AB We report on a high-dimensional method to globally profile glycoproteins that are modified with sialyl Lewis A or Lewis X glycans. Specifically, glycoproteins in serum or plasma are fractionated on a high-density antibody microarray (i.e., each are localized to their specific antibody spot) and are specifically detected via fluorescently labeled anti-sialyl Lewis A or anti-Lewis X antibodies with quantification in a microarray scanner. Non-glycosylated proteins or glycoproteins with other glycan motifs do not interfere with this assay. The whole process is very rapid and applicable for high-throughput screening without the need for purification of glycoproteins from the samples. Using these methods, sialyl Lewis A or Lewis X moieties were found to be expressed on many previously unreported secreted or membrane associated proteins. Furthermore, the combination of sialyl Lewis A or Lewis X content with protein level increased the ability of certain glycoproteins to distinguish 30 patients with stage III and IV colon cancer from 60 control samples. Thus, this highly sensitive method is capable of discovering novel specific glycan modifications on proteins, many of which will likely be useful for disease detection and monitoring.
Biological significance In this paper, we show that we can detect cancer-specific glycan Modifications on thousands of proteins using a high-density antibody array paired with a glycan specific antibody to probe the bound glycoproteins. To our knowledge, our array is by far the largest and densest that has ever been used for global profiling of specific glycan modification on proteins. Analysis of colon cancer patient plasma for sialyl Lewis A and Lewis X modifications revealed previously unknown protein carriers of these modifications and significant increases in these specific glycans on some proteins in people with cancer versus healthy controls, suggesting this method could be used to discover novel biomarkers. (C) 2013 Elsevier B.V. All rights reserved.
C1 [Rho, Jung-hyun; Mead, Judson R.; Lampe, Paul D.] Fred Hutchinson Canc Res Ctr, Human Biol Div, Translat Res Program, Seattle, WA 98109 USA.
[Rho, Jung-hyun; Mead, Judson R.; Lampe, Paul D.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
[Wright, W. Shea; Gildersleeve, Jeffrey C.] NCI, Biol Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA.
[Brenner, Dean E.] Univ Michigan, Med Ctr, EDRN, Great Lakes New England GLNE Clin Validat Ctr, Ann Arbor, MI 48109 USA.
[Stave, James W.] SDIX LLC, Newark, DE 19702 USA.
[Brenner, Dean E.] VA Med Ctr, Ann Arbor, MI 48105 USA.
RP Lampe, PD (reprint author), Fred Hutchinson Canc Res Ctr, M5-C800,1100 Fairview Ave North,Box 19024, Seattle, WA 98109 USA.
EM plampe@fhcrc.org
RI Gildersleeve, Jeffrey/N-3392-2014
FU National Institutes of Health as part of the Early Detection Research
Network [U01 CA152746, U01CA086400]; GI SPORE [P50 CA130810]; Kutsche
Family Memorial Chair in Internal Medicine; GRECC at the Ann Arbor VA
Medical Center
FX This work was funded in part by grants U01 CA152746 (PDL) and
U01CA086400 (DEB) from the National Institutes of Health as part of the
Early Detection Research Network, grant P50 CA130810 (GI SPORE (DEB)),
the Kutsche Family Memorial Chair in Internal Medicine (DEB) and the
GRECC at the Ann Arbor VA Medical Center. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Institutes of Health.
NR 30
TC 19
Z9 20
U1 3
U2 22
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1874-3919
EI 1876-7737
J9 J PROTEOMICS
JI J. Proteomics
PD JAN 16
PY 2014
VL 96
BP 291
EP 299
DI 10.1016/j.jprot.2013.10.030
PG 9
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA AB6RD
UT WOS:000331916300023
PM 24185138
ER
PT J
AU Park, SH
Rehermann, B
AF Park, Su-Hyung
Rehermann, Barbara
TI Immune Responses to HCV and Other Hepatitis Viruses
SO IMMUNITY
LA English
DT Review
ID T-CELL RESPONSES; NATURAL-KILLER-CELLS; INTERFERON REGULATORY FACTOR-3;
PERSISTENT LCMV INFECTION; SINGLE-SOURCE OUTBREAK; HIGHLY PATHOGENIC
SIV; INJECTION-DRUG USERS; C-VIRUS; VIRAL CLEARANCE; GENETIC-VARIATION
AB Five human hepatitis viruses cause most of the acute and chronic liver disease worldwide. Over the past 25 years, hepatitis C virus (HCV) in particular has received much interest because of its ability to persist in most immunocompetent adults and because of the lack of a protective vaccine. Here we examine innate and adaptive immune responses to HCV infection. Although HCV activates an innate immune response, it employs an elaborate set of mechanisms to evade interferon (IFN)-based antiviral immunity. By comparing innate and adaptive immune responses to HCV with those to hepatitis A and B viruses, we suggest that prolonged innate immune activation by HCV impairs the development of successful adaptive immune responses. Comparative immunology provides insights into the maintenance of immune protection. We conclude by discussing prospects for an HCV vaccine and future research needs for the hepatitis viruses.
C1 [Park, Su-Hyung; Rehermann, Barbara] NIDDK, Immunol Sect, Liver Dis Branch, NIH,DHHS, Bethesda, MD 20892 USA.
RP Rehermann, B (reprint author), NIDDK, Immunol Sect, Liver Dis Branch, NIH,DHHS, Bethesda, MD 20892 USA.
EM rehermann@nih.gov
RI Cheng, Yushao/E-6256-2011; Park, Su-Hyung/N-3514-2014
FU NIH, The National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK)
FX This work was supported by the Intramural Research Program of the NIH,
The National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK). We thank J. Kim for drawing Figure 1A.
NR 127
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U1 4
U2 36
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
EI 1097-4180
J9 IMMUNITY
JI Immunity
PD JAN 16
PY 2014
VL 40
IS 1
BP 13
EP 24
DI 10.1016/j.immuni.2013.12.010
PG 12
WC Immunology
SC Immunology
GA AB0JD
UT WOS:000331476900006
PM 24439265
ER
PT J
AU Turesson, I
Kovalchik, SA
Pfeiffer, RM
Kristinsson, SY
Goldin, LR
Drayson, MT
Landgren, O
AF Turesson, Ingemar
Kovalchik, Stephanie A.
Pfeiffer, Ruth M.
Kristinsson, Sigurdur Y.
Goldin, Lynn R.
Drayson, Mark T.
Landgren, Ola
TI Monoclonal gammopathy of undetermined significance and risk of lymphoid
and myeloid malignancies: 728 cases followed up to 30 years in Sweden
SO BLOOD
LA English
DT Article
ID SMOLDERING MULTIPLE-MYELOMA; SIGNIFICANCE MGUS; LONG-TERM;
TRANSFORMATION; PROGRESSION; CLASSIFICATION; PREVALENCE; MANAGEMENT;
PROGNOSIS; CRITERIA
AB In 728 Swedish cases of monoclonal gammopathy of undetermined significance (MGUS), followed up to 30 years (median, 10 years), we estimated the cumulative risk of hematologic disorders originating from lymphoid and myeloid lineages. Using Cox regression models, we examined associations of demographic and laboratory factors with progression and determined the discriminatory power of 3 prediction models for progression. Eighty-four MGUS cases developed a lymphoid disorder, representing a cumulative risk of 15.4%. Multiple myeloma (MM) occurred in 53 patients, and the 30-year cumulative risk was 10.6%; an similar to 0.5% annual risk. Three factors were significantly associated with progression: abnormal free light-chain (FLC) ratio (<0.26 or >1.65), M-protein concentration (>= 1.5 g/dL), and reduction of 1 or 2 noninvolved immunoglobulin isotype levels (immunoparesis). A prediction model with separate effects for these 3 factors and the M-protein isotype had higher discriminatory power than other models, although the differences were not statistically significant. The 30-year cumulative risk for myeloid malignancies was <2%. Our study confirms that abnormal FLC ratio and M-protein concentration > 1.5 g/dL, factors previously considered by Mayo Clinic researchers, are predictors for MM progression and suggests that separate consideration of immunoparesis and the Mayo Clinic risk factors could improve identification of MGUS patients at high risk for progression.
C1 [Turesson, Ingemar] Skane Univ Hosp, Dept Hematol & Coagulat Disorders, S-20502 Malmo, Sweden.
[Kovalchik, Stephanie A.; Pfeiffer, Ruth M.; Goldin, Lynn R.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Kristinsson, Sigurdur Y.] Natl Univ Hosp Reykjavik, Landspitali, Dept Hematol, Reykjavik, Iceland.
[Drayson, Mark T.] Univ Birmingham, Sch Med, Clin Immunol Serv, Edgbaston, England.
[Landgren, Ola] NCI, Multiple Myeloma Sect, Metab Branch, NIH, Bethesda, MD 20892 USA.
RP Turesson, I (reprint author), Skane Univ Hosp, Dept Hematol & Coagulat Disorders, S-20502 Malmo, Sweden.
EM Ingemar.turesson@med.lu.se
RI Kristinsson, Sigurdur /M-2910-2015
OI Kristinsson, Sigurdur /0000-0002-4964-7476
NR 27
TC 19
Z9 21
U1 0
U2 6
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD JAN 16
PY 2014
VL 123
IS 3
BP 338
EP 345
DI 10.1182/blood-2013-05-505487
PG 8
WC Hematology
SC Hematology
GA 290IP
UT WOS:000329748700013
PM 24222331
ER
PT J
AU Fields, RD
AF Fields, R. Douglas
TI Myelin Formation and Remodeling
SO CELL
LA English
DT Editorial Material
ID CNS
AB Myelin is a multilayer wrapping of insulation formed by glial cells around axons that is essential for rapid impulse transmission, but how glial cells accomplish this cellular choreography has long intrigued researchers. In this issue of Cell, Snaidero et al., provide new insights into how myelin forms and is remodeled.
C1 NICHD, NIH, Bethesda, MD 20892 USA.
RP Fields, RD (reprint author), NICHD, NIH, Bldg 35,Room 2A211, Bethesda, MD 20892 USA.
EM fieldsd@mail.nih.gov
FU Intramural NIH HHS [Z01 HD000713-13]
NR 10
TC 3
Z9 3
U1 1
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
EI 1097-4172
J9 CELL
JI Cell
PD JAN 16
PY 2014
VL 156
IS 1-2
BP 15
EP 17
DI 10.1016/j.cell.2013.12.038
PG 3
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 292OS
UT WOS:000329912200007
PM 24439366
ER
PT J
AU Lim, YH
Ovejero, D
Sugarman, JS
DeKlotz, CMC
Maruri, A
Eichenfield, LF
Kelley, PK
Juppner, H
Gottschalk, M
Tifft, CJ
Gafni, RI
Boyce, AM
Cowen, EW
Bhattacharyya, N
Guthrie, LC
Gahl, WA
Golas, G
Loring, EC
Overton, JD
Mane, SM
Lifton, RP
Levy, ML
Collins, MT
Choate, KA
AF Lim, Young H.
Ovejero, Diana
Sugarman, Jeffrey S.
DeKlotz, Cynthia M. C.
Maruri, Ann
Eichenfield, Lawrence F.
Kelley, Patrick K.
Jueppner, Harald
Gottschalk, Michael
Tifft, Cynthia J.
Gafni, Rachel I.
Boyce, Alison M.
Cowen, Edward W.
Bhattacharyya, Nisan
Guthrie, Lori C.
Gahl, William A.
Golas, Gretchen
Loring, Erin C.
Overton, John D.
Mane, Shrikant M.
Lifton, Richard P.
Levy, Moise L.
Collins, Michael T.
Choate, Keith A.
TI Multilineage somatic activating mutations in HRAS and NRAS cause mosaic
cutaneous and skeletal lesions, elevated FGF23 and hypophosphatemia
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID EPIDERMAL NEVUS-SYNDROME; D-RESISTANT RICKETS; MCCUNE-ALBRIGHT-SYNDROME;
FIBROBLAST GROWTH FACTOR-23; FAMILIAL TUMORAL CALCINOSIS;
HYPEROSTOSIS-HYPERPHOSPHATEMIA SYNDROME; CONGENITAL MELANOCYTIC NEVI;
N-RAS GENE; IN-VIVO; PHOSPHATE HOMEOSTASIS
AB Pathologically elevated serum levels of fibroblast growth factor-23 (FGF23), a bone-derived hormone that regulates phosphorus homeostasis, result in renal phosphate wasting and lead to rickets or osteomalacia. Rarely, elevated serum FGF23 levels are found in association with mosaic cutaneous disorders that affect large proportions of the skin and appear in patterns corresponding to the migration of ectodermal progenitors. The cause and source of elevated serum FGF23 is unknown. In those conditions, such as epidermal and large congenital melanocytic nevi, skin lesions are variably associated with other abnormalities in the eye, brain and vasculature. The wide distribution of involved tissues and the appearance of multiple segmental skin and bone lesions suggest that these conditions result from early embryonic somatic mutations. We report five such cases with elevated serum FGF23 and bone lesions, four with large epidermal nevi and one with a giant congenital melanocytic nevus. Exome sequencing of blood and affected skin tissue identified somatic activating mutations of HRAS or NRAS in each case without recurrent secondary mutation, and we further found that the same mutation is present in dysplastic bone. Our finding of somatic activating RAS mutation in bone, the endogenous source of FGF23, provides the first evidence that elevated serum FGF23 levels, hypophosphatemia and osteomalacia are associated with pathologic Ras activation and may provide insight in the heretofore limited understanding of the regulation of FGF23.
C1 [Lim, Young H.; Choate, Keith A.] Yale Univ, Sch Med, Dept Dermatol, New Haven, CT 06510 USA.
[Loring, Erin C.; Overton, John D.; Mane, Shrikant M.; Lifton, Richard P.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA.
[Lifton, Richard P.] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 USA.
[Ovejero, Diana; Gafni, Rachel I.; Boyce, Alison M.; Bhattacharyya, Nisan; Guthrie, Lori C.; Collins, Michael T.] Natl Inst Dental & Craniofacial Res, Skeletal Clin Studies Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA.
[Tifft, Cynthia J.; Gahl, William A.; Golas, Gretchen] NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA.
[Cowen, Edward W.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Ovejero, Diana] Univ Autonoma Barcelona, Dept Med, Bellaterra, Spain.
[Sugarman, Jeffrey S.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 95403 USA.
[Sugarman, Jeffrey S.] Univ Calif San Francisco, Dept Family Med, San Francisco, CA 95403 USA.
[DeKlotz, Cynthia M. C.; Eichenfield, Lawrence F.] Rady Childrens Hosp, Div Pediat & Adolescent Dermatol, San Diego, CA USA.
[Gottschalk, Michael] Rady Childrens Hosp, San Diego, CA USA.
[DeKlotz, Cynthia M. C.; Eichenfield, Lawrence F.] Univ Calif San Diego, Dept Pediat, San Diego, CA 92123 USA.
[DeKlotz, Cynthia M. C.; Eichenfield, Lawrence F.] Univ Calif San Diego, Dept Med Dermatol, San Diego, CA 92123 USA.
[Maruri, Ann; Gottschalk, Michael] Pediat Care Ogden, Ogden, UT USA.
[Maruri, Ann] Univ Utah, Coll Nursing, Salt Lake City, UT 84112 USA.
[Kelley, Patrick K.] Dell Childrens Med Ctr Cent Texas, Univ Med Ctr Brackenridge, Seton Inst Reconstruct Plast Surg, Austin, TX 78723 USA.
[Jueppner, Harald] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Nephrol Unit, Boston, MA 02114 USA.
[Jueppner, Harald] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA.
[Tifft, Cynthia J.; Gahl, William A.; Golas, Gretchen] NIH Common Fund, NIH Undiagnosed Dis Program, Bethesda, MD 20892 USA.
[Boyce, Alison M.] Childrens Natl Med Ctr, Div Orthopaed & Sports Med, Bone Hlth Program, Washington, DC 20010 USA.
[Loring, Erin C.; Overton, John D.; Mane, Shrikant M.; Lifton, Richard P.] Yale Ctr Mendelian Genom, New Haven, CT 06510 USA.
[Levy, Moise L.] Univ Texas SW Med Ctr Dallas, Dept Dermatol, Dallas, TX 75390 USA.
[Levy, Moise L.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
[Levy, Moise L.] Baylor Coll Med, Dept Dermatol, Houston, TX 77030 USA.
RP Collins, MT (reprint author), Natl Inst Dental & Craniofacial Res, Skeletal Clin Studies Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA.
EM mcollins@dir.nidcr.nih.gov; keith.choate@yale.edu
OI DeKlotz, Cynthia/0000-0002-6410-8710
FU Doris Duke Charitable Foundation; Yale Center for Mendelian Genomics
(NIH) [U54 HG006504]; Yale University School of Medicine; "la Caixa"
Fellowship Program; Division of Intramural Research, National Institutes
of Dental and Craniofacial Research, NIH
FX This work was supported by a Doris Duke Charitable Foundation Clinical
Scientist Development Award to K. A. C. and by the Yale Center for
Mendelian Genomics (NIH U54 HG006504). Y.H.L. was supported by the Paul
H. Lavietes, M. D. Student Research Fellowship from the Yale University
School of Medicine. D.O. was supported by the "la Caixa" Fellowship
Program. M. T. C. and R. I. G. were supported by the Division of
Intramural Research, National Institutes of Dental and Craniofacial
Research, NIH.
NR 117
TC 18
Z9 18
U1 0
U2 7
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 JAN 15
PY 2014
VL 23
IS 2
BP 397
EP 407
DI 10.1093/hmg/ddt429
PG 11
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA AA1EX
UT WOS:000330840400010
PM 24006476
ER
PT J
AU Li, YY
Umbach, DM
Li, LP
AF Li, Yuanyuan
Umbach, David M.
Li, Leping
TI T-KDE: a method for genome-wide identification of constitutive protein
binding sites from multiple ChIP-seq data sets
SO BMC GENOMICS
LA English
DT Article
DE Binding pattern; ChIP-seq; Kernel density estimation; Binary range tree;
Mode-finding; Constitutive site; CTCF code
ID TOPOLOGICAL DOMAINS; MAMMALIAN GENOMES; DENSITY-FUNCTION; DNA
METHYLATION; TILING ARRAYS; ALGORITHM; DISCOVERY; REGIONS; MODEL
AB a Background: A protein may bind to its target DNA sites constitutively, i.e., regardless of cell type. Intuitively, constitutive binding sites should be biologically functional. A prerequisite for understanding their functional relevance is knowing all their locations for a protein of interest. Genome-wide discovery of constitutive binding sites requires robust and efficient computational methods to integrate results from numerous binding experiments. Such methods are lacking, however.
Results: To locate constitutive binding sites for a protein using ChIP-seq data for that protein from multiple cell lines, we developed a method, T-KDE, which combines a binary range tree with a kernel density estimator. Using 132 CTCF (CCCTC-binding factor) ChIP-seq datasets, we showed that the number of constitutive sites identified by T-KDE is robust to the choice of tuning parameter and that T-KDE identifies binding site locations more accurately than a binning approach. Furthermore, T-KDE can identify constitutive sites that are missed by a motif-based approach either because a bound site failed to reach the motif significance cutoff or because the peak sequence scanned was too short. By studying sites declared constitutive by T-KDE but not by the motif-based approach, we discovered two new CTCF motif variants. Using ENCODE data on 22 transcription factors (TF) in 132 cell lines, we identified constitutive binding sites for each TF and provide evidence that, for some TFs, they may be biologically meaningful.
Conclusions: T-KDE is an efficient and effective method to predict constitutive protein binding sites using ChIP-seq peaks from multiple cell lines. Besides constitutive binding sites for a given protein, T-KDE can identify genomic "hot spots" where several different proteins bind and, conversely, cell-type-specific sites bound by a given protein.
C1 [Li, Yuanyuan; Umbach, David M.; Li, Leping] NIEHS, Biostat Branch, Morrisville, NC 27709 USA.
RP Li, LP (reprint author), NIEHS, Biostat Branch, Morrisville, NC 27709 USA.
EM li3@niehs.nih.gov
FU Computational Biology Facility at NIEHS; Intramural Research Program of
the NIH, National Institute of Environmental Health Sciences [ES101765]
FX We thank Liang Niu and Weichun Huang for discussion and Xuting Wang and
Grace Kissling for critical reading of the manuscript. We thank the
Computational Biology Facility at NIEHS for computing time and support.
This research was supported by Intramural Research Program of the NIH,
National Institute of Environmental Health Sciences (ES101765).
NR 34
TC 1
Z9 1
U1 1
U2 5
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 JAN 15
PY 2014
VL 15
AR 27
DI 10.1186/1471-2164-15-27
PG 12
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA AA4VN
UT WOS:000331094800001
PM 24428924
ER
PT J
AU Karas, MG
Benkeser, D
Arnold, AM
Bartz, TM
Djousse, L
Mukamal, KJ
Ix, JH
Zieman, SJ
Siscovick, DS
Tracy, RP
Mantzoros, CS
Gottdiener, JS
Defilippi, CR
Kizer, JR
AF Karas, Maria G.
Benkeser, David
Arnold, Alice M.
Bartz, Traci M.
Djousse, Luc
Mukamal, Kenneth J.
Ix, Joachim H.
Zieman, Susan J.
Siscovick, David S.
Tracy, Russell P.
Mantzoros, Christos S.
Gottdiener, John S.
deFilippi, Christopher R.
Kizer, Jorge R.
TI Relations of Plasma Total and High-Molecular-Weight Adiponectin to
New-Onset Heart Failure in Adults >= 65 Years of Age (from the
Cardiovascular Health Study)
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID LEFT-VENTRICULAR HYPERTROPHY; DIASTOLIC FUNCTION; OLDER PERSONS;
DISEASE; RISK; MASS; MEN; ASSOCIATION; RESISTANCE; MORTALITY
AB Adiponectin exhibits cardioprotective properties in experimental studies, but elevated levels have been linked to increased mortality in older adults and patients with chronic heart failure (HF). The adipokine's association with new-onset HF remains less well defined. The aim of this study,was to investigate the associations of total and high-molecular weight (HMW) adiponectin with incident HF (n = 780) and, in a subset, echocardiographic parameters in a community-based cohort of adults aged >= 65 years. Total and HMW adiponectin were measured in 3,228 subjects without prevalent HF, atrial fibrillation or CVD. The relations of total and HMW adiponectin with HF were nonlinear, with significant associations observed only for concentrations greater than the median (12.4 and 6.2 mg/L, respectively). After adjustment for potential confounders, the hazard ratios per SD increment in total adiponectin were 0.93 (95% confidence interval 0.72 to 1.21) for concentrations less than the median and 1.25 (95% confidence interval 1.14 to 1.38) higher than the median. There was a suggestion of effect modification by body mass index, whereby the association appeared strongest in participants with lower body mass indexes. Consistent with the HF findings, higher adiponectin tended to be associated with left ventricular systolic dysfunction and left atrial enlargement. Results were similar for HMW adiponectin. In conclusion, total and HMW adiponectin showed comparable relations with incident HF in this older cohort, with a threshold effect of increasing risk occurring at their median concentrations. High levels of adiponectin may mark or mediate age-related processes that lead to HF in older adults. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Karas, Maria G.] Weill Cornell Med Coll, Dept Med, New York, NY USA.
[Benkeser, David; Arnold, Alice M.; Bartz, Traci M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Siscovick, David S.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Siscovick, David S.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Djousse, Luc] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA.
[Djousse, Luc; Mantzoros, Christos S.] Harvard Univ, Sch Med, Boston, MA USA.
[Mukamal, Kenneth J.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA.
[Mantzoros, Christos S.] Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA.
[Ix, Joachim H.] Vet Affairs San Diego Healthcare Syst, Nephrol Sect, San Diego, CA USA.
[Ix, Joachim H.] Univ Calif San Diego, Dept Med, Div Nephrol, San Diego, CA 92103 USA.
[Ix, Joachim H.] Univ Calif San Diego, Dept Family & Prevent Med, Div Prevent Med, San Diego, CA 92103 USA.
[Zieman, Susan J.] NIA, Div Geriatr & Clin Gerontol, Bethesda, MD 20892 USA.
[Tracy, Russell P.] Univ Vermont, Dept Pathol, Colchester, VT USA.
[Tracy, Russell P.] Univ Vermont, Dept Biochem, Colchester, VT USA.
[Mantzoros, Christos S.] Boston Vet Affairs Healthcare Syst, Endocrinol Sect, Boston, MA USA.
[Gottdiener, John S.; deFilippi, Christopher R.] Univ Maryland, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21201 USA.
[Kizer, Jorge R.] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA.
[Kizer, Jorge R.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
RP Kizer, JR (reprint author), Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA.
EM jorge.kizer@einstein.yu.edu
RI Djousse, Luc/F-5033-2017;
OI Djousse, Luc/0000-0002-9902-3047; Karas, Maria/0000-0002-8763-6460
FU National Heart, Lung, and Blood Institute, Bethesda, Maryland
[HL080295]; National Institute on Aging [AG023629]; [R01 HL-094555];
[HHSN268201200036C]; [N01HC85239]; [N01 HC55222]; [N01HC85079];
[N01HC85080]; [N01HC85081]; [N01HC85082]; [N01HC85083];
[N01HC85084]; [N01HC85086]; [N01HC35129]
FX This work was supported by Grant R01 HL-094555, Contracts
HHSN268201200036C, N01HC85239; N01 HC55222, N01HC85079, N01HC85080,
N01HC85081, N01HC85082, N01HC85083, N01HC85084, N01HC85086, and
N01HC35129, and Grant HL080295 from the National Heart, Lung, and Blood
Institute, Bethesda, Maryland, with additional contribution from the
National Institute of Neurological Disorders and Stroke. Additional
support was provided by Grant AG023629 from the National Institute on
Aging. A full list of principal Cardiovascular Health Study (CHS)
investigators and institutions can be found at http://www.chs-nhlbi.org.
NR 30
TC 15
Z9 15
U1 0
U2 2
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
EI 1879-1913
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD JAN 15
PY 2014
VL 113
IS 2
BP 328
EP 334
DI 10.1016/j.amjcard.2013.09.027
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 297KI
UT WOS:000330253900022
PM 24169012
ER
PT J
AU Boca, SM
Sinha, R
Cross, AJ
Moore, SC
Sampson, JN
AF Boca, Simina M.
Sinha, Rashmi
Cross, Amanda J.
Moore, Steven C.
Sampson, Joshua N.
TI Testing multiple biological mediators simultaneously
SO BIOINFORMATICS
LA English
DT Article
ID FATTY-ACIDS; CANCER; MODELS; COLON
AB Motivation: Modern biomedical and epidemiological studies often measure hundreds or thousands of biomarkers, such as gene expression or metabolite levels. Although there is an extensive statistical literature on adjusting for 'multiple comparisons' when testing whether these biomarkers are directly associated with a disease, testing whether they are biological mediators between a known risk factor and a disease requires a more complex null hypothesis, thus offering additional methodological challenges.
Results: We propose a permutation approach that tests multiple putative mediators and controls the family wise error rate. We demonstrate that, unlike when testing direct associations, replacing the Bonferroni correction with a permutation approach that focuses on the maximum of the test statistics can significantly improve the power to detect mediators even when all biomarkers are independent. Through simulations, we show the power of our method is 2-5x larger than the power achieved by Bonferroni correction. Finally, we apply our permutation test to a case-control study of dietary risk factors and colorectal adenoma to show that, of 149 test metabolites, docosahexaenoate is a possible mediator between fish consumption and decreased colorectal adenoma risk.
C1 [Boca, Simina M.; Sinha, Rashmi; Cross, Amanda J.; Moore, Steven C.; Sampson, Joshua N.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
RP Sampson, JN (reprint author), NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
EM joshua.sampson@nih.gov
RI Sinha, Rashmi/G-7446-2015; Moore, Steven/D-8760-2016
OI Sinha, Rashmi/0000-0002-2466-7462; Moore, Steven/0000-0002-8169-1661
FU Intramural Research Program of the Division of Cancer Epidemiology and
Genetics, National Cancer Institute, National Institutes of Health (NIH)
FX Support was from the Intramural Research Program of the Division of
Cancer Epidemiology and Genetics, National Cancer Institute, National
Institutes of Health (NIH). Computation was performed using the Biowulf
Linux cluster at the National Institutes of Health, Bethesda, Maryland
(http://biowulf.nih.gov).
NR 25
TC 2
Z9 2
U1 0
U2 5
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 JAN 15
PY 2014
VL 30
IS 2
BP 214
EP 220
DI 10.1093/bioinformatics/btt633
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 299YV
UT WOS:000330432500009
PM 24202540
ER
PT J
AU Lucassen, EA
Piaggi, P
Dsurney, J
de Jonge, L
Zhao, XC
Mattingly, MS
Ramer, A
Gershengorn, J
Csako, G
Cizza, G
AF Lucassen, Eliane A.
Piaggi, Paolo
Dsurney, John
de Jonge, Lilian
Zhao, Xiong-ce
Mattingly, Megan S.
Ramer, Angela
Gershengorn, Janet
Csako, Gyorgy
Cizza, Giovanni
CA Sleep Extension Study Grp
TI Sleep Extension Improves Neurocognitive Functions in Chronically
Sleep-Deprived Obese Individuals
SO PLOS ONE
LA English
DT Article
ID PERFORMANCE; DURATION; QUALITY; DEPRIVATION; IMPAIRMENT; DEFICITS;
MEMORY; ADULTS; INDEX; APNEA
AB Background: Sleep deprivation and obesity, are associated with neurocognitive impairments. Effects of sleep deprivation and obesity on cognition are unknown, and the cognitive long-term effects of improvement of sleep have not been prospectively assessed in short sleeping, obese individuals.
Objective: To characterize neurocognitive functions and assess its reversibility.
Design: Prospective cohort study.
Setting: Tertiary Referral Research Clinical Center.
Patients: A cohort of 121 short-sleeping (<6.5 h/night) obese (BMI 30-55 kg/m(2)) men and pre-menopausal women.
Intervention: Sleep extension (468 +/- 88 days) with life-style modifications. Measurements: Neurocognitive functions, sleep quality and sleep duration.
Results: At baseline, 44% of the individuals had an impaired global deficit score (t-score 0-39). Impaired global deficit score was associated with worse subjective sleep quality (p = 0.02), and lower urinary dopamine levels (p = 0.001). Memory was impaired in 33%; attention in 35%; motor skills in 42%; and executive function in 51% of individuals. At the final evaluation (N = 74), subjective sleep quality improved by 24% (p<0.001), self-reported sleep duration increased by 11% by questionnaires (p<0.001) and by 4% by diaries (p = 0.04), and daytime sleepiness tended to improve (p = 0.10). Global cognitive function and attention improved by 7% and 10%, respectively (both p = 0.001), and memory and executive functions tended to improve (p = 0.07 and p = 0.06). Serum cortisol increased by 17% (p = 0.02). In a multivariate mixed model, subjective sleep quality and sleep efficiency, urinary free cortisol and dopamine and plasma total ghrelin accounted for 1/5 of the variability in global cognitive function.
Limitations: Drop-out rate.
Conclusions: Chronically sleep-deprived obese individuals exhibit substantial neurocognitive deficits that are partially reversible upon improvement of sleep in a non-pharmacological way. These findings have clinical implications for large segments of the US population.
C1 [Lucassen, Eliane A.; Dsurney, John; Csako, Gyorgy] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Lucassen, Eliane A.] Leiden Univ, Neurophysiol Lab, Dept Mol Cell Biol, Med Ctr, Leiden, Netherlands.
[Dsurney, John] Ctr Neurosci & Regenerat Med, Bethesda, MD USA.
[Zhao, Xiong-ce] NIDDK, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[de Jonge, Lilian; Mattingly, Megan S.; Ramer, Angela; Gershengorn, Janet; Cizza, Giovanni] NIDDK, Sect Neuroendocrinol Obes, NIH, Bethesda, MD 20892 USA.
[Piaggi, Paolo] Univ Hosp Pisa, Endocrinol Unit, Obes Res Ctr, Pisa, Italy.
[Csako, Gyorgy] NIH, Ctr Clin, Dept Lab Med, Bethesda, MD 20892 USA.
RP Cizza, G (reprint author), NIDDK, Sect Neuroendocrinol Obes, NIH, Bethesda, MD 20892 USA.
EM gcizza@gmail.com
OI de Jonge, Lilian/0000-0001-5900-0695; Piaggi, Paolo/0000-0003-2774-9161
FU National Institutes of Health (NIH), Intramural Research Programs at the
National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK); National Institutes of Health (NIH), Clinical Center;
Fulbright; VSBfonds; Leiden University Fund
FX This study was supported by the National Institutes of Health (NIH),
Intramural Research Programs at the National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK) and Clinical Center. EAL received
scholarships from Fulbright, VSBfonds and the Leiden University Fund.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 43
TC 5
Z9 5
U1 3
U2 14
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 JAN 15
PY 2014
VL 9
IS 1
AR e84832
DI 10.1371/journal.pone.0084832
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 297DH
UT WOS:000330235100035
PM 24482677
ER
PT J
AU Ricketts, CJ
Hill, VK
Linehan, WM
AF Ricketts, Christopher J.
Hill, Victoria K.
Linehan, W. Marston
TI Tumor-Specific Hypermethylation of Epigenetic Biomarkers, Including
SFRP1, Predicts for Poorer Survival in Patients from the TCGA Kidney
Renal Clear Cell Carcinoma (KIRC) Project
SO PLOS ONE
LA English
DT Article
ID WNT ANTAGONIST GENE; SUPPRESSOR GENE; DNA METHYLATION; PROMOTER
METHYLATION; CANCER; PROGRESSION; FBN2; IDENTIFICATION; INACTIVATION;
EXPRESSION
AB The recent publication of the TCGA Kidney Renal Clear Cell Carcinoma (KIRC) project has provided an immense wealth and breadth of data providing an invaluable tool for confirmation and expansion upon previous observations in a large data set containing multiple data types including DNA methylation, somatic mutation, and clinical information. In clear cell renal cell carcinoma (CCRCC) many genes have been demonstrated to be epigenetically inactivated by promoter hypermethylated and in a small number of cases to be associated with clinical outcome. This study created two cohorts based on the Illumina BeadChip array used to confirm the frequency of tumor-specific hypermethylation of these published hypermethylated genes, assess the impact of somatic mutation or chromosomal loss and provide the most comprehensive assessment to date of the association of this hypermethylation with patient survival. Hypermethylation of the Fibrillin 2 (FBN2) gene was the most consistent epigenetic biomarker for CCRCC across both cohorts in 40.2% or 52.5% of tumors respectively. Hypermethylation of the secreted frizzled-related protein 1 (SFRP1) gene and the basonuclin 1 (BNC1) gene were both statistically associated with poorer survival in both cohorts (SFRP1 - p=<0.0001 or 0.0010 and BNC1 - p=<0.0001 or 0.0380) and represented better independent markers of survival than tumor stage, grade or dimension in one cohort and tumor stage or dimension in the other cohort. Loss of the SFRP1 protein can potentially activate the WNT pathway and this analysis highlighted hypermethylation of several other WNT pathway regulating genes and demonstrated a poorer survival outcome for patients with somatic mutation of these genes. The success of demethylating drugs in hematological malignances and the current trials in solid tumors suggest that the identification of clinically relevant hypermethylated genes combined with therapeutic advances may improve the effectiveness and usefulness of such drugs in clear cell renal cell carcinoma.
C1 [Ricketts, Christopher J.; Linehan, W. Marston] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Hill, Victoria K.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Linehan, WM (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM WML@nih.gov
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research
FX This research was supported in part by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 48
TC 11
Z9 11
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 JAN 15
PY 2014
VL 9
IS 1
AR e85621
DI 10.1371/journal.pone.0085621
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 297DH
UT WOS:000330235100106
PM 24454902
ER
PT J
AU Teicher, BA
AF Teicher, Beverly A.
TI Targets in small cell lung cancer
SO BIOCHEMICAL PHARMACOLOGY
LA English
DT Article
DE Small cell lung cancer; SCLC; CD24; CD56; Myc
ID NEUROENDOCRINE TUMORS; IN-VITRO; C-MYC; STEM-CELLS; EXPRESSION; GROWTH;
RECEPTOR; LINES; METASTASIS; ADHESION
AB Recurrent small cell lung cancer is a recalcitrant malgnancy. The application of genomic technologies has begun to elucidate the large number of genetic abnormalities in SCLC. Several cell surface receptors are known to be overexpressed by SCLC in clinic specimens and cell in culture including GPCRs such as the bradykinin receptor, the chemokine receptor CXCR4, the vasopression receeptor and the three bomebsin receptors. The glucose transporter GLUT1, the tetraspanin family member PETA/CD151 and the immunoglobulin superfamily member ALCAM/CD166 are also overexpressed by SCLC. NCAM/CD56 is overexpressed by nearly all SCLC and is currently the target for an antibody drug conjugate in Phase II trial. Although SCLC is not considered a RTK driven disease, IGF1R and FGFRs are often overexpressed by SCLC. SCLC abberantly expresses several developmental transcription factors including ASCL1, SOX2, 4, and 11, OCT4, NANOG, PAX5; however, overexpression of MYC may be a driver in SCLC. Like other cancers, SCLC expresses survival factors and uses aerobic glycolysis as a major source of ATP. The drawback of many ponteial targets overexpressed by SCLC is expression of the same proteins by normal tissues. We are slowly learning more about the molecular abnormalities that occur in SCLC; however, therapeutic impact from new findings remains a goal to work toward. Published by Elsevier Inc.
C1 [Teicher, Beverly A.] NCI, Bethesda, MD 20892 USA.
RP Teicher, BA (reprint author), NCI, Mol Pharmacol Branch, RM 4-W602,MSC 9735,9609 Med Ctr Dr, Bethesda, MD 20892 USA.
EM teicherba@mail.nih.gov
NR 79
TC 25
Z9 26
U1 1
U2 26
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0006-2952
EI 1873-2968
J9 BIOCHEM PHARMACOL
JI Biochem. Pharmacol.
PD JAN 15
PY 2014
VL 87
IS 2
BP 211
EP 219
DI 10.1016/j.bcp.2013.09.014
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 298OD
UT WOS:000330332800001
PM 24091017
ER
PT J
AU Xu, H
Ye, D
Behra, M
Burgess, S
Chen, SH
Lin, F
AF Xu, Hui
Ye, Ding
Behra, Martine
Burgess, Shawn
Chen, Songhai
Lin, Fang
TI G beta 1 controls collective cell migration by regulating the protrusive
activity of leader cells in the posterior lateral line primordium
SO DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE Zebrafish; G protein; G beta 1; Posterior lateral line primordium; Cell
migration
ID BETA-GAMMA-SUBUNITS; CHEMOKINE RECEPTOR CXCR4; ACTIN CYTOSKELETON;
TISSUE MIGRATION; IN-VIVO; F-ACTIN; ZEBRAFISH; MORPHOGENESIS; CANCER;
ROLES
AB Collective cell migration is critical for normal development, tissue repair and cancer metastasis. Migration of the posterior lateral line primordium (pLLP) generates the zebrafish sensory organs (neuromasts, NMs). This migration is promoted by the leader cells at the leading edge of the pLLP, which express the G protein-coupled chemokine receptor Cxcr4b and respond to the chemokine Cxcl12a. However, the mechanism by which Cxcl12a/Cxcr4b signaling regulates pLLP migration remains unclear. Here we report that signal transduction by the heterotrimeric G protein subunit G beta 1 is essential for proper pLLP migration. Although both G beta 1 and G beta 4 are expressed in the pLLP and NMs, depletion of G beta 1 but not G beta 4 resulted in an arrest of pLLP migration. In embryos deficient for G beta 1, the pLLP cells migrated in an uncoordinated fashion and were unable to extend protrusions at the leading front, phenocopying those in embryos deficient for Cxcl12a or Cxcr4b. A transplantation assay showed that, like Cxcr4b, G beta 1 is required only in the leader cells of the pLLP. Analysis of F-actin dynamics in the pLLP revealed that whereas wild-type leader cells display extensive actin polymerization in the direction of pLLP migration, counterparts defective for GO, Cxcr4b or Cxcl12a do not. Finally, synergy experiments revealed that G beta 1 and Cxcr4b interact genetically in regulating pLLP migration. Collectively, our data indicate that G beta 1 controls migration of the pLLP, likely by acting downstream of the Cxcl12a/Cxcr4b signaling. This study also provides compelling evidence for functional specificity among G beta isoforms in vivo. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Xu, Hui; Ye, Ding; Lin, Fang] Univ Iowa, Carver Coll Med, Dept Anat & Cell Biol, Iowa City, IA 52242 USA.
[Chen, Songhai] Univ Iowa, Carver Coll Med, Dept Pharmacol, Iowa City, IA 52242 USA.
[Behra, Martine] Univ Puerto Rico, Dept Anat & Neurobiol, San Juan, PR 00936 USA.
[Burgess, Shawn] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
RP Lin, F (reprint author), Univ Iowa, Carver Coll Med, Dept Anat & Cell Biol, Iowa City, IA 52242 USA.
EM fang-lin@uiowa.edu
FU NIH/NCRR [K99R00RR024119, AHA12GRNT11670009, AHA10GRNT3620015, NIH
R01GM094255]
FX This study is supported by Grants: NIH/NCRR K99R00RR024119 and
AHA12GRNT11670009 (to FL); AHA10GRNT3620015 and NIH R01GM094255 (to SC).
We thank Laurent Gamba and Christine Dambly-Chaudiere (Universite
Montpellier II, France) for providing the 139 bp cxcr4b promoter, and
Kacey Mersch, Xiaoyun Tang, Zhizeng Sun and Catherine Wang for technical
support.
NR 64
TC 10
Z9 10
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 0012-1606
EI 1095-564X
J9 DEV BIOL
JI Dev. Biol.
PD JAN 15
PY 2014
VL 385
IS 2
BP 316
EP 327
DI 10.1016/j.ydbio.2013.10.027
PG 12
WC Developmental Biology
SC Developmental Biology
GA 296SM
UT WOS:000330205700016
PM 24201188
ER
PT J
AU Sodt, AJ
Sandar, ML
Gawrisch, K
Pastor, RW
Lyman, E
AF Sodt, Alexander J.
Sandar, Michael Logan
Gawrisch, Klaus
Pastor, Richard W.
Lyman, Edward
TI The Molecular Structure of the Liquid-Ordered Phase of Lipid Bilayers
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID PHOSPHOLIPID-MEMBRANES; PLASMA-MEMBRANES; ACYL CHAIN; CHOLESTEROL;
DYNAMICS; DOMAINS; SIMULATION; COMPLEXES; MIXTURES; RAFTS
AB Molecular dynamics simulations reveal substructures within the liquid-ordered phase Of lipid bilayers. These substructures, identified in a 10 mu s all-atom trajectory of liquid-ordered/liquid-disordered coexistence (L-o/L-d) are composed of saturated hydrocarbon chains packed with local hexagonal order and separated by interstitial regions enriched in cholesterol and unsaturated chains. Lipid hydrocarbon chain order parameters calculated from the L-o phase are in excellent agreement with H-2 NMR measurements; the local hexagonal packing is also consistent with H-1-MAS NMR spectra of the L-o phase, NMR diffusion experiments, and,small-angle X-ray and neutron scattering. The balance of cholesterol-rich to local hexagonal order is proposed to control the partitioning of membrane components L-o regions. The latter have frequently associated with formation of so-called rafts, platforms in the plasma membranes of cells that facilitate interaction between components of signaling pathways.
C1 [Sodt, Alexander J.; Pastor, Richard W.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Gawrisch, Klaus] NIAAA, NIH, Bethesda, MD 20892 USA.
[Sandar, Michael Logan; Lyman, Edward] Univ Delaware, Dept Phys & Astrophys, Newark, DE 19716 USA.
[Lyman, Edward] Univ Delaware, Dept Chem & Biochem, Newark, DE 19716 USA.
RP Lyman, E (reprint author), Univ Delaware, Dept Phys & Astrophys, Newark, DE 19716 USA.
EM elyman@udel.edu
FU National Institutes of Health (NIH) [P41GM103712-S1]; National Institute
on Alcohol Abuse and Alcoholism; National Heart, Lung, and Blood
Institute of the NIH
FX We thank Sarah Veatch for acquisition of the 2H NMR spectra.
Anton computer time was provided by-the National Resource for Biomedical
Supercomputing (NRBSC), the Pittsburgh Supercomputing Center (PSC), and
the BTRC for Multiscale Modeling of Biological Systems (MMBioS) through
Grant P41GM103712-S1 from the National Institutes of Health (NIH). The
Anton machine at NRBSC/PSC was generously made available by D. E. Shaw
Research. This research was supported in part by the Intramural Research
Programs of the National Institute on Alcohol Abuse and Alcoholism, and
National Heart, Lung, and Blood Institute of the NIH, and utilized the
NHLBI LoBoS cluster.
NR 55
TC 46
Z9 46
U1 6
U2 96
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 JAN 15
PY 2014
VL 136
IS 2
BP 725
EP 732
DI 10.1021/ja4105667
PG 8
WC Chemistry, Multidisciplinary
SC Chemistry
GA 294BY
UT WOS:000330018600037
PM 24345334
ER
PT J
AU Blackwell, TS
Tager, AM
Borok, Z
Moore, BB
Schwartz, DA
Anstrom, KJ
Bar-Joseph, Z
Bitterman, P
Blackburn, MR
Bradford, W
Brown, KK
Chapman, HA
Collard, HR
Cosgrove, GP
Deterding, R
Doyle, R
Flaherty, KR
Garcia, CK
Hagood, JS
Henke, CA
Herzog, E
Hogaboam, CM
Horowitz, JC
King, TE
Loyd, JE
Lawson, WE
Marsh, CB
Noble, PW
Noth, I
Sheppard, D
Olsson, J
Ortiz, LA
O'Riordan, TG
Oury, TD
Raghu, G
Roman, J
Sime, PJ
Sisson, TH
Tschumperlin, D
Violette, SM
Weaver, TE
Wells, RG
White, ES
Kaminski, N
Martinez, FJ
Wynn, TA
Thannickal, VJ
Eu, JP
AF Blackwell, Timothy S.
Tager, Andrew M.
Borok, Zea
Moore, Bethany B.
Schwartz, David A.
Anstrom, Kevin J.
Bar-Joseph, Ziv
Bitterman, Peter
Blackburn, Michael R.
Bradford, William
Brown, Kevin K.
Chapman, Harold A.
Collard, Harold R.
Cosgrove, Gregory P.
Deterding, Robin
Doyle, Ramona
Flaherty, Kevin R.
Garcia, Christine Kim
Hagood, James S.
Henke, Craig A.
Herzog, Erica
Hogaboam, Cory M.
Horowitz, Jeffrey C.
King, Talmadge E., Jr.
Loyd, James E.
Lawson, William E.
Marsh, Clay B.
Noble, Paul W.
Noth, Imre
Sheppard, Dean
Olsson, Julie
Ortiz, Luis A.
O'Riordan, Thomas G.
Oury, Tim D.
Raghu, Ganesh
Roman, Jesse
Sime, Patricia J.
Sisson, Thomas H.
Tschumperlin, Daniel
Violette, Shelia M.
Weaver, Timothy E.
Wells, Rebecca G.
White, Eric S.
Kaminski, Naftali
Martinez, Fernando J.
Wynn, Thomas A.
Thannickal, Victor J.
Eu, Jerry P.
TI Future Directions in Idiopathic Pulmonary Fibrosis Research
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
DE idiopathic pulmonary fibrosis; alveolar epithelial cells; extracellular
matrix; interstitial lung disease; inflammation
ID MUC5B PROMOTER POLYMORPHISM; SURFACTANT PROTEIN-C; GROWTH-FACTOR-BETA;
ENDOPLASMIC-RETICULUM STRESS; GENOME-WIDE ASSOCIATION; SERUM AMYLOID P;
LUNG FIBROSIS; MESENCHYMAL TRANSITION; CIRCULATING FIBROCYTES; LIVER
FIBROSIS
AB The median survival of patients with idiopathic pulmonary fibrosis (IPF) continues to be approximately 3 years from the time of diagnosis, underscoring the lack of effective medical therapies for this disease. In the United States alone, approximately 40,000 patients die of this disease annually. In November 2012, the NHLBI held a workshop aimed at coordinating research efforts and accelerating the development of IPF therapies. Basic, translational, and clinical researchers gathered with representatives from the NHLBI, patient advocacy groups, pharmaceutical companies, and the U. S. Food and Drug Administration to review the current state of IPF research and identify priority areas, opportunities for collaborations, and directions for future research. The workshop was organized into groups that were tasked with assessing and making recommendations to promote progress in one of the following six critical areas of research: (1) biology of alveolar epithelial injury and aberrant repair; (2) role of extracellular matrix; (3) preclinical modeling; (4) role of inflammation and immunity; (5) genetic, epigenetic, and environmental determinants; (6) translation of discoveries into diagnostics and therapeutics. The workshop recommendations provide a basis for directing future research and strategic planning by scientific, professional, and patient communities and the NHLBI.
C1 [Blackwell, Timothy S.; Loyd, James E.; Lawson, William E.] Vanderbilt Univ, Med Ctr, Nashville, TN USA.
[Tager, Andrew M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Borok, Zea] Univ So Calif, Los Angeles, CA USA.
[Moore, Bethany B.; Flaherty, Kevin R.; Hogaboam, Cory M.; Horowitz, Jeffrey C.; Sisson, Thomas H.; White, Eric S.; Martinez, Fernando J.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Schwartz, David A.; Brown, Kevin K.; Cosgrove, Gregory P.; Deterding, Robin] Natl Jewish Hlth, Denver, CO USA.
[Schwartz, David A.; Brown, Kevin K.; Cosgrove, Gregory P.; Deterding, Robin] Univ Colorado, Denver, CO 80202 USA.
[Anstrom, Kevin J.] Duke Clin Res Inst, Durham, NC USA.
[Bar-Joseph, Ziv; Kaminski, Naftali] Carnegie Mellon Univ, Pittsburgh, PA 15213 USA.
[Bitterman, Peter; Henke, Craig A.] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA.
[Blackburn, Michael R.] Univ Texas Houston, Med Sch Houston, Houston, TX USA.
[Bradford, William] InterMune Inc, Brisbane, CA USA.
[Chapman, Harold A.; Collard, Harold R.; King, Talmadge E., Jr.; Sheppard, Dean] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Doyle, Ramona; Olsson, Julie] Genentech Roche, San Francisco, CA USA.
[Garcia, Christine Kim] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Hagood, James S.] Univ Calif San Diego, San Diego, CA 92103 USA.
[Herzog, Erica] Yale Univ, Sch Med, New Haven, CT USA.
[Marsh, Clay B.] Ohio State Univ, Columbus, OH 43210 USA.
[Noble, Paul W.] Cedars Sinai Med Ctr, Los Angeles, CA USA.
[Noth, Imre] Univ Chicago, Chicago, IL 60637 USA.
[Ortiz, Luis A.; Oury, Tim D.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
[O'Riordan, Thomas G.] Gilead Sci Inc, Foster City, CA 94404 USA.
[Raghu, Ganesh] Univ Washington, Med Ctr, Seattle, WA 98195 USA.
[Roman, Jesse] Univ Louisville, Louisville, KY 40292 USA.
[Sime, Patricia J.] Univ Rochester, Sch Med, Rochester, NY USA.
[Tschumperlin, Daniel] Harvard Sch Publ Hlth, Boston, MA USA.
[Violette, Shelia M.] Biogen Idec Inc, Cambridge, MA USA.
[Weaver, Timothy E.] Cincinnati Childrens Res Fdn, Cincinnati, OH USA.
[Wells, Rebecca G.] Univ Penn, Philadelphia, PA 19104 USA.
[Wynn, Thomas A.] NIAID, Bethesda, MD 20892 USA.
[Thannickal, Victor J.] Univ Alabama Birmingham, Birmingham, AL USA.
[Eu, Jerry P.] NHLBI, Bethesda, MD 20892 USA.
RP Eu, JP (reprint author), NHLBI, Natl Inst Hlth, Div Lung Dis, 6701 Rockledge Dr,Rockledge Ctr II,Room 10042, Bethesda, MD 20892 USA.
EM jerry.eu@nih.gov
RI ortiz, luis/H-9851-2013; hogaboam, cory /M-3578-2014
FU NHLBI; National Institutes of Health
FX Supported by NHLBI, National Institutes of Health.
NR 113
TC 59
Z9 61
U1 0
U2 33
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 JAN 15
PY 2014
VL 189
IS 2
BP 214
EP 222
DI 10.1164/rccm.201306-1141WS
PG 9
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 290VG
UT WOS:000329785900015
PM 24160862
ER
PT J
AU Fung, KL
Pan, J
Ohnuma, S
Lund, PE
Pixley, JN
Kimchi-Sarfaty, C
Ambudkar, SV
Gottesman, MM
AF Fung, King Leung
Pan, James
Ohnuma, Shinobu
Lund, Paul E.
Pixley, Jessica N.
Kimchi-Sarfaty, Chava
Ambudkar, Suresh V.
Gottesman, Michael M.
TI MDR1 Synonymous Polymorphisms Alter Transporter Specificity and Protein
Stability in a Stable Epithelial Monolayer
SO CANCER RESEARCH
LA English
DT Article
ID MULTIDRUG-RESISTANCE GENE; P-GLYCOPROTEIN ABCB1; HAPLOTYPE PROFILES; ATP
HYDROLYSIS; CELL-LINES; EXPRESSION; BINDING; DRUGS; VARIANT; DISPOSITION
AB The drug efflux function of P-glycoprotein (P-gp) encoded by MDR1 can be influenced by genetic polymorphisms, including two synonymous changes in the coding region of MDR1. Here we report that the conformation of P-gp and its drug efflux activity can be altered by synonymous polymorphisms in stable epithelial monolayers expressing P-gp. Several cell lines with similar MDR1 DNA copy number were developed and termed LLC-MDR1-WT (expresses wild-type P-gp), LLC-MDR1-3H (expresses common haplotype P-gp), and LLC-MDR1-3HA (a mutant that carries a different valine codon in position 3435). These cell lines express similar levels of recombinant mRNA and protein. P-gp in each case is localized on the apical surface of polarized cells. However, the haplotype and its mutant P-gps fold differently from the wild-type, as determined by UIC2 antibody shift assays and limited proteolysis assays. Surface biotinylation experiments suggest that the non-wild-type P-gps have longer recycling times. Drug transport assays show that wild-type and haplotype P-gp respond differently to P-gp inhibitors that block efflux of rhodamine 123 or mitoxantrone. In addition, cytotoxicity assays show that the LLC-MDR1-3H cells are more resistant to mitoxantrone than the LLC-MDR1-WT cells after being treated with a P-gp inhibitor. Expression of polymorphic P-gp, however, does not affect the host cell's morphology, growth rate, or monolayer formation. Also, ATPase activity assays indicate that neither basal nor drug-stimulated ATPase activities are affected in the variant P-gps. Taken together, our findings indicate that "silent" polymorphisms significantly change P-gp function, which would be expected to affect interindividual drug disposition and response. (C)2013 AACR.
C1 [Fung, King Leung; Pan, James; Ohnuma, Shinobu; Lund, Paul E.; Pixley, Jessica N.; Ambudkar, Suresh V.; Gottesman, Michael M.] NCI, Lab Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Kimchi-Sarfaty, Chava] US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA.
RP Gottesman, MM (reprint author), NCI, Lab Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM mgottesman@nih.gov
FU Intramural Research Program of the NIH, National Cancer Institute
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute.
NR 48
TC 36
Z9 38
U1 1
U2 6
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD JAN 15
PY 2014
VL 74
IS 2
BP 598
EP 608
DI 10.1158/0008-5472.CAN-13-2064
PG 11
WC Oncology
SC Oncology
GA 294HB
UT WOS:000330034200019
PM 24305879
ER
PT J
AU Neckers, L
Trepel, JB
AF Neckers, Len
Trepel, Jane B.
TI Stressing the Development of Small Molecules Targeting HSP90
SO CLINICAL CANCER RESEARCH
LA English
DT Editorial Material
ID CELL LUNG-CANCER
AB Inhibitors of the molecular chaperone HSP90 have been in clinical development as anticancer agents since 1999. Recent clinical studies, including the work of Saif and colleagues in this issue of Clinical Cancer Research, demonstrate that significant progress has been made in overcoming the obstacles preventing regulatory approval. (C) 2013 AACR.
C1 [Neckers, Len] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
[Trepel, Jane B.] NCI, Dev Therapeut Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Neckers, L (reprint author), NCI, 9000 Rockville Pike,Bldg 10 CRC,Room 1-5940, Bethesda, MD 20892 USA.
EM len@helix.nih.gov
NR 12
TC 23
Z9 23
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JAN 15
PY 2014
VL 20
IS 2
BP 275
EP 277
DI 10.1158/1078-0432.CCR-13-2571
PG 3
WC Oncology
SC Oncology
GA 292QZ
UT WOS:000329918600001
PM 24166908
ER
PT J
AU Turcotte, S
Gros, A
Tran, E
Lee, CCR
Wunderlich, JR
Robbins, PF
Rosenberg, SA
AF Turcotte, Simon
Gros, Alena
Tran, Eric
Lee, Chyi-Chia R.
Wunderlich, John R.
Robbins, Paul F.
Rosenberg, Steven A.
TI Tumor-Reactive CD8(+) T Cells in Metastatic Gastrointestinal Cancer
Refractory to Chemotherapy
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID INFILTRATING LYMPHOCYTES; MELANOMA PATIENTS; COLORECTAL-CANCER;
AUTOLOGOUS TUMOR; DOSE INTERLEUKIN-2; ADOPTIVE TRANSFER; TRANSFER
THERAPY; PHASE-II; ANTIGEN; PHENOTYPE
AB Purpose: To evaluate whether patients with metastatic gastrointestinal adenocarcinomas refractory to chemotherapy harbor tumor-reactive cytotoxic T cells.
Experimental Design: Expansion of CD8(+) tumor-infiltrating lymphocytes (TIL) and cancer cell lines was attempted from gastrointestinal cancer metastases in 16 consecutive patients for the study of antitumor immune recognition. Retroviral transduction of genes encoding T-cell receptors (TCR) was used to define HLA-restriction elements and specific reactivity.
Results: TIL were expanded from metastases in all patients, and new tumor cell lines were generated in 5 patients. Autologous tumor recognition without cross-reactivity against allogeneic HLA-matched gastrointestinal tumors was found in CD8(+) TIL from 3 of these 5 patients. In a patient with gastric cancer liver metastases, the repertoire of CD8(+) TIL was dominated by cytolytic sister clones reactive to 2 out of 4 autologous cancer cell lines restricted by HLA-C*0701. From the same patient, a rare CD8(+) TIL clone with a distinct TCR recognized all four cancer cell lines restricted by HLA-B*4901. In a patient with bile duct cancer, two distinct antitumor cytolytic clones were isolated from a highly polyclonal CD8(+) TIL repertoire. TCRs isolated from these clones recognized epitopes restricted by HLA-A*0201. In a third patient, CD8(+) TIL reactivity was progressively lost against an autologous colon cancer cell line that displayed loss of HLA haplotype.
Conclusions: This study provides a basis for the development of immunotherapy for patients with advanced gastrointestinal malignancies by first establishing the presence of naturally occurring tumorreactive CD8(+) TIL at the molecular level. (C) 2013 AACR.
C1 [Turcotte, Simon; Gros, Alena; Tran, Eric; Wunderlich, John R.; Robbins, Paul F.; Rosenberg, Steven A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
[Lee, Chyi-Chia R.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
RP Rosenberg, SA (reprint author), NCI, 10 Ctr Dr MSC 1201,CRC Room 3-3940, Bethesda, MD 20892 USA.
EM sar@nih.gov
OI Gros, Alena/0000-0002-1207-1880
FU Intramural Research Program of the NIH, NCI, Center for Cancer Research
FX This work was supported by the Intramural Research Program of the NIH,
NCI, Center for Cancer Research.
NR 50
TC 11
Z9 12
U1 1
U2 8
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 JAN 15
PY 2014
VL 20
IS 2
BP 331
EP 343
DI 10.1158/1078-0432.CCR-13-1736
PG 13
WC Oncology
SC Oncology
GA 292QZ
UT WOS:000329918600009
PM 24218514
ER
PT J
AU Jain, N
Curran, E
Iyengar, NM
Diaz-Flores, E
Kunnavakkam, R
Popplewell, L
Kirschbaum, MH
Karrison, T
Erba, HP
Green, M
Poire, X
Koval, G
Shannon, K
Reddy, PL
Joseph, L
Atallah, EL
Dy, P
Thomas, SP
Smith, SE
Doyle, LA
Stadler, WM
Larson, RA
Stock, W
Odenike, O
AF Jain, Nitin
Curran, Emily
Iyengar, Neil M.
Diaz-Flores, Ernesto
Kunnavakkam, Rangesh
Popplewell, Leslie
Kirschbaum, Mark H.
Karrison, Theodore
Erba, Harry P.
Green, Margaret
Poire, Xavier
Koval, Greg
Shannon, Kevin
Reddy, Poluru L.
Joseph, Loren
Atallah, Ehab L.
Dy, Philip
Thomas, Sachdev P.
Smith, Scott E.
Doyle, L. Austin
Stadler, Walter M.
Larson, Richard A.
Stock, Wendy
Odenike, Olatoyosi
TI Phase II Study of the Oral MEK Inhibitor Selumetinib in Advanced Acute
Myelogenous Leukemia: A University of Chicago Phase II Consortium Trial
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID ACUTE MYELOID-LEUKEMIA; KINASE KINASE-1/2 INHIBITOR; PAPILLARY
THYROID-CARCINOMA; INTERNATIONAL WORKING GROUP; CELL LUNG-CANCER; N-RAS
MUTATIONS; AZD6244 ARRY-142886; OPEN-LABEL; METASTATIC MELANOMA;
MEDIATES RESISTANCE
AB Purpose: The clinical relevance of targeting the RAS/RAF/MEK/ERK pathway, activated in 70% to 80% of patients with acute myelogenous leukemia (AML), is unknown.
Experimental Design: Selumetinib is an oral small-molecule inhibitor of MAP-ERK kinase (MEK)-1/2. Forty-seven patients with relapsed/refractory AML or 60 years old or more with untreated AML were enrolled on a phase II study. Patients were stratified by FLT3 ITD mutation status. The primary endpoint was response rate (complete, partial, and minor). Leukemia cells were analyzed for extracellular signal-regulated kinase (ERK) and mTOR phosphorylation.
Results: Common drug-related toxicities were grade 1-2 diarrhea, fatigue, nausea, vomiting, and skin rash. In the FLT3 wild-type cohort, six of 36 (17%) patients had a response [one partial response, three minor responses, two unconfirmed minor responses (uMR)]. No patient with FLT3 ITD responded. NRAS and KRAS mutations were detected in 7% and 2% of patients, respectively. The sole patient with KRAS mutation had uMR with hematologic improvement in platelets. Baseline p-ERK activation was observed in 85% of patients analyzed but did not correlate with a response. A single-nucleotide polymorphism (SNP) rs3733542 in exon 18 of the KIT gene was detected in significantly higher number of patients with response/stable disease compared with nonresponders (60% vs. 23%; P = 0.027).
Conclusions: Selumetinib is associated with modest single-agent antileukemic activity in advanced AML. However, given its favorable toxicity profile, combination with drugs that target other signaling pathways in AML should be considered. The potential association of SNP rs3733542 in exon 18 of the KIT gene with antileukemic activity of selumetinib is intriguing, but will require validation in larger trials. (C)2013 AACR.
C1 [Jain, Nitin; Curran, Emily; Iyengar, Neil M.; Kunnavakkam, Rangesh; Karrison, Theodore; Green, Margaret; Poire, Xavier; Koval, Greg; Reddy, Poluru L.; Joseph, Loren; Stadler, Walter M.; Larson, Richard A.; Stock, Wendy; Odenike, Olatoyosi] Univ Chicago, Chicago, IL 60637 USA.
[Dy, Philip] Decatur Mem Hosp, Decatur, GA USA.
[Thomas, Sachdev P.] Illinois Canc Care, Peoria, IL USA.
[Smith, Scott E.] Loyola Univ, Med Ctr, Maywood, IL 60153 USA.
[Diaz-Flores, Ernesto; Shannon, Kevin] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Popplewell, Leslie; Kirschbaum, Mark H.] City Hope Natl Med Ctr, Duarte, CA USA.
[Erba, Harry P.] Univ Michigan, Med Ctr, Ann Arbor, MI USA.
[Atallah, Ehab L.] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Doyle, L. Austin] NCI, Rockville, MD USA.
RP Odenike, O (reprint author), Univ Chicago, Dept Med, Hematol Oncol Sect, 5841 South Maryland,MC 2115, Chicago, IL 60637 USA.
EM todenike@medicine.bsd.uchicago.edu
FU NCI Cancer Therapy and Evaluation Program [N01-CM-62201]; AstraZeneca
Pharmaceuticals; NCI Translational Research Funds; Specialized Center of
Research grant of the Leukemia and Lymphoma Society [7015-09]
FX This work was supported by the NCI Cancer Therapy and Evaluation Program
contract N01-CM-62201, AstraZeneca Pharmaceuticals, NCI Translational
Research Funds, and Specialized Center of Research grant (# 7015-09) of
the Leukemia and Lymphoma Society.
NR 50
TC 36
Z9 37
U1 0
U2 6
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 JAN 15
PY 2014
VL 20
IS 2
BP 490
EP 498
DI 10.1158/1078-0432.CCR-13-1311
PG 9
WC Oncology
SC Oncology
GA 292QZ
UT WOS:000329918600023
PM 24178622
ER
PT J
AU Ilango, A
Kesner, AJ
Keller, KL
Stuber, GD
Bonci, A
Ikemoto, S
AF Ilango, Anton
Kesner, Andrew J.
Keller, Kristine L.
Stuber, Garret D.
Bonci, Antonello
Ikemoto, Satoshi
TI Similar Roles of Substantia Nigra and Ventral Tegmental Dopamine Neurons
in Reward and Aversion
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE dopamine; dorsal striatum; drug abuse; Parkinson's disease; substantia
nigra; ventral tegmental area
ID MIDBRAIN; STRIATUM; REINFORCEMENT; RECOMBINASE; ACTIVATION; PROJECTION;
PATHWAYS; INPUTS
AB Dopamine neurons in the ventral tegmental area (VTA) are implicated in affective functions. However, it is unclear to what extent dopamine neurons in substantia nigra pars compacta (SNc) play such roles. TH-Cre transgenic mice received adeno-associated viral vectors encoding channelrhodopsin2 (ChR2), halorhodopsin (NpHR), or control vector into the VTA or SNc, resulting in selective expression of these opsins in dopamine neurons. Mice with ChR2 learned instrumental responding to deliver photostimulation into the VTA or SNc and also sought for the compartment where they received photostimulation (i.e., operant place preference). Operant place preference scores were highly correlated with self-stimulation responses. In contrast, mice with NpHR avoided the compartment where they received photostimulation into the VTA, SNc, or dorsal striatum, whereas control mice did not. These observations suggest that the excitation and inhibition of SNc dopamine neurons elicit positive and negative affective effects, respectively, similar to those of VTA dopamine neurons.
C1 [Ilango, Anton; Kesner, Andrew J.; Keller, Kristine L.; Bonci, Antonello; Ikemoto, Satoshi] NIDA, Intramural Res Program, NIH, US Dept Hlth & Human Serv, Baltimore, MD 21014 USA.
[Stuber, Garret D.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA.
RP Ikemoto, S (reprint author), NIDA IRP, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA.
EM satoshi.ikemoto@nih.gov
RI Stuber, Garret/E-1160-2011;
OI Ikemoto, Satoshi/0000-0002-0732-7386; Kesner, Andrew/0000-0002-3902-1955
FU Intramural Research Program of National Institute on Drug Abuse,
National Institutes of Health
FX This work was supported by the Intramural Research Program of National
Institute on Drug Abuse, National Institutes of Health. We thank the
NIDA-IRP Optogenetics and Transgenic Technology Core for providing viral
vectors, the Microscopy Core for imaging help, and Drs Jennifer Bossert,
Ikue Kusumoto, and Ross McDevitt for technical assistance.
NR 33
TC 60
Z9 60
U1 1
U2 18
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD JAN 15
PY 2014
VL 34
IS 3
BP 817
EP 822
DI 10.1523/JNEUROSCI.1703-13.2014
PG 6
WC Neurosciences
SC Neurosciences & Neurology
GA 292QH
UT WOS:000329916600015
PM 24431440
ER
PT J
AU Tost, H
Callicott, JH
Rasetti, R
Vakkalanka, R
Mattay, VS
Weinberger, DR
Law, AJ
AF Tost, Heike
Callicott, Joseph H.
Rasetti, Roberta
Vakkalanka, Radhakrishna
Mattay, Venkata S.
Weinberger, Daniel R.
Law, Amanda J.
TI Effects of Neuregulin 3 Genotype on Human Prefrontal Cortex Physiology
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE ErbB4; genetics; Neuregulin; neuroimaging; NRG3; schizophrenia
ID COGNITIVE CONTROL; SCHIZOPHRENIA; LINKAGE; RISK; GENE; ARCHITECTURE;
FAMILIES; DISORDER; BRAIN; SCAN
AB The neuregulin 3 gene (NRG3) plays pleiotropic roles in neurodevelopment and is a putative susceptibility locus for schizophrenia. Specifically, the T allele of NRG3 rs10748842 has been associated with illness risk, altered cognitive function, and the expression of a novel splice isoform in prefrontal cortex (PFC), but the neural system effects are unexplored. Here, we report an association between rs10748842 and PFC physiology as measured by functional magnetic resonance imaging of human working memory performance, where a convincing link between increased genetic risk for schizophrenia and increased activation in some PFC areas has been established. In 410 control individuals (195 males, 215 females), we detected a highly significant effect of NRG3 genotype manifesting as an unanticipated increase in ventrolateral PFC activation in nonrisk-associated C allele carriers. An additional analysis including 78 patients with schizophrenia spectrum disorders (64 males, 14 females) and 123 unaffected siblings (53 males, 70 females) revealed a whole-brain significant genotype by group interaction in right dorsolateral PFC (DLPFC), manifesting as a relative activation increase in healthy controls and siblings (C > T/T) and as a hypoactivation in patients (T/T > C). These observed genotype-dependent effects in PFC were not explained by task performance and did not conform to established locales of prefrontal inefficiency linked to genetic risk for schizophrenia. Our data indicate a complex modulation of brain physiology by rs10748842, which does not fit the simple inefficiency model of risk association in DLPFC and suggests that other neurobiological mechanisms are involved.
C1 [Tost, Heike; Callicott, Joseph H.; Rasetti, Roberta; Vakkalanka, Radhakrishna; Mattay, Venkata S.; Weinberger, Daniel R.; Law, Amanda J.] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Tost, Heike] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Psychiat & Psychotherapy, D-61859 Mannheim, Germany.
[Vakkalanka, Radhakrishna; Mattay, Venkata S.; Weinberger, Daniel R.] Johns Hopkins Univ, Lieber Inst Brain Dev, Baltimore, MD 21205 USA.
[Weinberger, Daniel R.] Johns Hopkins Sch Med, Dept Psychiat, Baltimore, MD 21205 USA.
[Weinberger, Daniel R.] Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
[Weinberger, Daniel R.] Johns Hopkins Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
[Weinberger, Daniel R.] Johns Hopkins Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA.
[Law, Amanda J.] Univ Colorado, Sch Med, Dept Psychiat, Aurora, CO 80045 USA.
[Law, Amanda J.] Univ Colorado, Sch Med, Dept Cell & Dev Biol, Aurora, CO 80045 USA.
RP Law, AJ (reprint author), Univ Colorado, Sch Med, Mailstop 8344,RC1 North,RM 8101, Aurora, CO 80045 USA.
EM amanda.law@ucdenver.edu
RI Callicott, Joseph/C-9102-2009;
OI Callicott, Joseph/0000-0003-1298-3334; Law, Amanda/0000-0002-2574-1564
FU Intramural Research Program of the National Institute of Mental Health,
National Institutes of Health
FX This work was supported by funds from the Intramural Research Program of
the National Institute of Mental Health, National Institutes of Health.
NR 25
TC 6
Z9 6
U1 0
U2 7
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 JAN 15
PY 2014
VL 34
IS 3
BP 1051
EP 1056
DI 10.1523/JNEUROSCI.3496-13.2014
PG 6
WC Neurosciences
SC Neurosciences & Neurology
GA 292QH
UT WOS:000329916600037
PM 24431462
ER
PT J
AU Kupchik, YM
Scofield, MD
Rice, KC
Cheng, KJ
Roques, BP
Kalivas, PW
AF Kupchik, Yonatan M.
Scofield, Michael D.
Rice, Kenner C.
Cheng, Kejun
Roques, Bernard P.
Kalivas, Peter W.
TI Cocaine Dysregulates Opioid Gating of GABA Neurotransmission in the
Ventral Pallidum
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE addiction; cocaine; electrophysiology; enkephalin; mu opioid receptor;
ventral pallidum
ID GABAERGIC SYNAPTIC-TRANSMISSION; MESSENGER-RNA EXPRESSION;
ENKEPHALIN-LIKE MATERIAL; FREELY MOVING RATS; NUCLEUS-ACCUMBENS; INDUCED
REINSTATEMENT; GLOBUS-PALLIDUS; TEGMENTAL AREA; MEDIATING COCAINE;
RECEPTOR-ACTIVITY
AB The ventral pallidum (VP) is a target of dense nucleus accumbens projections. Many of these projections coexpress GABA and the neuropeptide enkephalin, a delta and mu opioid receptor (MOR) ligand. Of these two, the MOR in the VP is known to be involved in reward-related behaviors, such as hedonic responses to palatable food, alcohol intake, and reinstatement of cocaine seeking. Stimulating MORs in the VP decreases extracellular GABA, indicating that the effects of MORs in the VP on cocaine seeking are via modulating GABA neurotransmission. Here, we use whole-cell patch-clamp on a rat model of withdrawal from cocaine self-administration to test the hypothesis that MORs presynaptically regulate GABA transmission in the VP and that cocaine withdrawal changes the interaction between MORs and GABA. We found that in cocaine-extinguished rats pharmacological activation of MORs no longer presynaptically inhibited GABA release, whereas blocking the MORs disinhibited GABA release. Moreover, MOR-dependent long-term depression of GABA neurotransmission in the VP was lost in cocaine-extinguished rats. Last, GABA neurotransmission was found to be tonically suppressed in cocaine-extinguished rats. These substantial synaptic changes indicated that cocaine was increasing tone on MOR receptors. Accordingly, increasing endogenous tone by blocking the enzymatic degradation of enkephalin inhibited GABA neurotransmission in yoked saline rats but not in cocaine-extinguished rats. In conclusion, our results indicate that following withdrawal from cocaine self-administration enkephalin levels in the VP are elevated and the opioid modulation of GABA neurotransmission is impaired. This may contribute to the difficulties withdrawn addicts experience when trying to resist relapse.
C1 [Kupchik, Yonatan M.; Scofield, Michael D.; Kalivas, Peter W.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA.
[Rice, Kenner C.; Cheng, Kejun] NIDA, Chem Biol Res Branch, Rockville, MD 20892 USA.
[Rice, Kenner C.; Cheng, Kejun] NIAAA, Rockville, MD 20892 USA.
[Roques, Bernard P.] Pharmaleads SAS, F-75013 Paris, France.
[Roques, Bernard P.] Univ Paris 05, F-75006 Paris, France.
RP Kalivas, PW (reprint author), Med Univ S Carolina, Dept Neurosci, 96 Jonathan Lucas St, Charleston, SC 29425 USA.
EM kupchik@musc.edu; kalivasp@musc.edu
OI Kupchik, Yonatan/0000-0003-3732-4933
FU National Institutes of Health [DA015369, DA003906, DA012513];
Neuroscience Institute Fellowship for International Trainees, Medical
University of South Carolina; Intramural Research Programs of the
National Institute on Drug Abuse and National Institute on Alcohol and
Alcoholism
FX This work was supported by Grants DA015369, DA003906, and DA012513 from
the National Institutes of Health and by the Neuroscience Institute
Fellowship for International Trainees, Medical University of South
Carolina. A portion of this work was supported by the Intramural
Research Programs of the National Institute on Drug Abuse and National
Institute on Alcohol and Alcoholism.
NR 64
TC 8
Z9 11
U1 1
U2 8
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD JAN 15
PY 2014
VL 34
IS 3
BP 1057
EP 1066
DI 10.1523/JNEUROSCI.4336-13.2014
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 292QH
UT WOS:000329916600038
PM 24431463
ER
PT J
AU Fatemi, M
Paul, TA
Brodeur, GM
Shokrani, B
Brim, H
Ashktorab, H
AF Fatemi, Mehrnaz
Paul, Thomas A.
Brodeur, Garrett M.
Shokrani, Babak
Brim, Hassan
Ashktorab, Hassan
TI Epigenetic Silencing of CHD5, a Novel Tumor-Suppressor Gene, Occurs in
Early Colorectal Cancer Stages
SO CANCER
LA English
DT Article
DE CHD5; colon cancer; promoter; histone; African Americans
ID PROMOTER HYPERMETHYLATION; DNA METHYLATION; GASTRIC-CANCER;
OVARIAN-CANCER; CPG ISLANDS; NEUROBLASTOMA; INVOLVEMENT; DISEASE;
FAMILY; 1P36
AB BACKGROUNDChromodomain helicase DNA binding protein 5 (CHD5) is a family member of chromatin remodeling factors. The epigenetic silencing mechanisms of CHD5 in colorectal cancer have not been well studied.
METHODSHere we analyzed CHD5 methylation and mRNA expression in vitro and in clinical samples from African American patients. DNA and RNA were isolated from formalin fixed paraffin embedded (FFPE) colon tissues. DNA was tested for methylation using methylation-specific polymerase chain reation (PCR) and bisulfite sequencing. RNA was used for mRNA quantification using qRT-PCR. The RKO cell line was treated with 5-Aza-dC and SAHA. RKO cells were also stably transfected with a CHD5-expressing vector. The transcriptional activity was studied in the 1 kb upstream region of the CHD5 promoter using the dual reporter assay. We performed cell proliferation, migration, and invasion assays using the RKO cell line.
RESULTSIn most adenoma samples, CHD5 expression was not detected in contrast to normal tissues. In RKO cells, CHD5 silencing was associated with DNA methylation and repressive histone modifications. CHD5 expression was restored after treatment with 5-Aza-dC and SAHA. CHD5 reactivation reduced cell proliferation, migration, and invasion. The reporter assay indicated that the main regulatory region of the CHD5 promoter is encompassed in the -489 to -823 region with important transcriptional regulatory sites (TCF/LEF, SP1, and AP-2).
CONCLUSIONSThe CHD5 gene is repressed in all types of adenomas, either epigenetically or by chromosomal deletion. CHD5 activity is regulated by DNA methylation and repressive histone modifications. CHD5 likely acts as a tumor-suppressor gene in early colorectal carcinogenesis. Cancer 2014;120:172-180. (c) 2013 American Cancer Society.
Colorectal cancer develops through an adenoma-adenocarcinoma carcinogenesis process, and this sequential process is driven by 3 molecular pathways: chromosomal instability, microsatellite instability, and CpG island methylation. This study was conducted to explore whether the CHD5 gene acts as a tumor-suppressor or oncogene in colon cancer.
C1 [Fatemi, Mehrnaz; Ashktorab, Hassan] Howard Univ, Coll Med, Dept Med, Washington, DC USA.
[Fatemi, Mehrnaz; Ashktorab, Hassan] Howard Univ, Coll Med, Ctr Canc, Washington, DC USA.
[Paul, Thomas A.] NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA.
[Brodeur, Garrett M.] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA.
[Shokrani, Babak; Brim, Hassan] Howard Univ, Coll Med, Dept Pathol, Washington, DC USA.
RP Ashktorab, H (reprint author), Howard Univ Hosp, Dept Med, Ctr Canc, 2041 Georgia Ave NW, Washington, DC 20060 USA.
EM hashktorab@howard.edu
FU National Institute on Minority Health and Health Disparities of the
National Institutes of Health [G12MD007597]; National Center for
Advancing Translational Sciences (NCATS), National Institutes of Health,
through the Clinical and Translational Science Awards Program (CTSA)
[UL1TR000101, UL1RR031975]
FX This project was supported (in part) by the National Institute on
Minority Health and Health Disparities of the National Institutes of
Health under Award Number G12MD007597. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Institutes of Health." And by Federal
funds (UL1TR000101 previously UL1RR031975) from the National Center for
Advancing Translational Sciences (NCATS), National Institutes of Health,
through the Clinical and Translational Science Awards Program (CTSA), a
trademark of DHHS, part of the Roadmap Initiative, "Re-Engineering the
Clinical Research Enterprise."
NR 39
TC 14
Z9 15
U1 0
U2 14
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 JAN 15
PY 2014
VL 120
IS 2
BP 172
EP 180
DI 10.1002/cncr.28316
PG 9
WC Oncology
SC Oncology
GA 284QC
UT WOS:000329334000006
PM 24243398
ER
PT J
AU Kim, TA
Kang, JM
Hyun, JS
Lee, B
Kim, SJ
Yang, ES
Hong, S
Lee, HJ
Fujii, M
Niederhuber, JE
Kim, SJ
AF Kim, Tae-Aug
Kang, Jin Muk
Hyun, Ja-Shil
Lee, Bona
Kim, Staci Jakyong
Yang, Eun-Sung
Hong, Suntaek
Lee, Ho-Jae
Fujii, Makiko
Niederhuber, John E.
Kim, Seong-Jin
TI The Smad7-Skp2 complex orchestrates Myc stability, impacting on the
cytostatic effect of TGF-beta
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
DE Myc; Smad7; Skp2; Protein stability; Ubiquitylation
ID GROWTH-FACTOR-BETA; BOX PROTEIN SKP2; C-MYC; UBIQUITIN LIGASE;
TRANSCRIPTIONAL ACTIVATION; CELL-PROLIFERATION; DEGRADATION;
PHOSPHORYLATION; RECEPTOR; ID2
AB In most human cancers the Myc proto-oncogene is highly activated. Dysregulation of Myc oncoprotein contributes to tumorigenesis in numerous tissues and organs. Thus, targeting Myc stability could be a crucial step for cancer therapy. Here we report Smad7 as a key molecule regulating Myc stability and activity by recruiting the F-box protein, Skp2. Ectopic expression of Smad7 downregulated the protein level of Myc without affecting the transcription level, and significantly repressed its transcriptional activity, leading to inhibition of cell proliferation and tumorigenic activity. Furthermore, Smad7 enhanced ubiquitylation of Myc through direct interaction with Myc and recruitment of Skp2. Ablation of Smad7 resulted in less sensitivity to the growth inhibitory effect of TGF-beta by inducing stable Myc expression. In conclusion, these findings that Smad7 functions in Myc oncoprotein degradation and enhances the cytostatic effect of TGF-beta signaling provide a possible new therapeutic approach for cancer treatment.
C1 [Kim, Tae-Aug; Kang, Jin Muk; Hyun, Ja-Shil; Lee, Bona; Kim, Staci Jakyong; Kim, Seong-Jin] CHA Univ, CHA Canc Inst, Seoul 135081, South Korea.
[Kim, Tae-Aug; Yang, Eun-Sung; Niederhuber, John E.] NCI, Canc Cell Biol Branch, Bethesda, MD 20892 USA.
[Lee, Bona] Sookmyung Womens Univ, Coll Pharm, Seoul 140742, South Korea.
[Hong, Suntaek; Lee, Ho-Jae] Gachon Univ Med & Sci, Dept Mol Med, Inchon 406840, South Korea.
[Fujii, Makiko] Aichi Canc Ctr, Res Inst, Nagoya, Aichi 4648681, Japan.
RP Kim, TA (reprint author), CHA Univ, CHA Canc Inst, Seoul 135081, South Korea.
EM takim@cha.ac.kr; kimsj@cha.ac.kr
FU National Research foundation of Korea [2009-0081756]; Intramural
Research Program of the National Cancer Institute, NIH, Bethesda, MD
FX This research was supported by the National Research foundation of Korea
[grant number 2009-0081756 to S.-J.K. and T.-A.K.] and the Intramural
Research Program of the National Cancer Institute, NIH, Bethesda, MD.
The NCI had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript. Deposited in PMC
for release after 12 months.
NR 57
TC 5
Z9 5
U1 0
U2 2
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0021-9533
EI 1477-9137
J9 J CELL SCI
JI J. Cell Sci.
PD JAN 15
PY 2014
VL 127
IS 2
BP 411
EP 421
DI 10.1242/jcs.136028
PG 11
WC Cell Biology
SC Cell Biology
GA 290WM
UT WOS:000329789200016
PM 24259667
ER
PT J
AU Duveau, DY
Yasgar, A
Wang, YH
Hu, X
Kouznetsova, J
Brimacombe, KR
Jadhav, A
Simeonov, A
Thomas, CJ
Maloney, DJ
AF Duveau, Damien Y.
Yasgar, Adam
Wang, Yuhong
Hu, Xin
Kouznetsova, Jennifer
Brimacombe, Kyle R.
Jadhav, Ajit
Simeonov, Anton
Thomas, Craig J.
Maloney, David J.
TI Structure-activity relationship studies and biological characterization
of human NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase
inhibitors
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE HPGD; 15-PGDH; Prostaglandin; PGE(2); Inhibitor
ID CATALYZED N-ARYLATION; 15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2); CANCER;
IMIDAZOLES; PATHWAY; ACID
AB The structure-activity relationship (SAR) study of two chemotypes identified as inhibitors of the human NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase (HPGD, 15-PGDH) was conducted. Top compounds from both series displayed potent inhibition (IC50 < 50 nM), demonstrate excellent selectivity towards HPGD and potently induce PGE(2) production in A549 lung cancer and LNCaP prostate cancer cells. Published by Elsevier Ltd.
C1 [Duveau, Damien Y.; Yasgar, Adam; Wang, Yuhong; Hu, Xin; Kouznetsova, Jennifer; Brimacombe, Kyle R.; Jadhav, Ajit; Simeonov, Anton; Thomas, Craig J.; Maloney, David J.] NIH, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA.
RP Maloney, DJ (reprint author), NIH, Natl Ctr Adv Translat Sci, 9800 Med Ctr Dr, Rockville, MD 20850 USA.
EM maloneyd@mail.nih.gov
FU Molecular Libraries Initiative of the National Institutes of Health
Roadmap for Medical Research [U54MH084681]; Intramural Research Program
of the National Center for Advancing Translational Sciences at the
National Institutes of Health
FX We thank Jim Bougie, Thomas Daniel and William Leister for compound
purification, as well as Danielle van Leer, Misha Itkin, Crystal
Mcknight, Christopher LeClair and Paul Shinn for assistance with
compound management. We also thank Udo Oppermann at the Structural
Genomics Consortium (SGC), Oxford, UK for providing the ALDH1A1 and
HSD17 beta 4 enzymes. This research was supported by the Molecular
Libraries Initiative of the National Institutes of Health Roadmap for
Medical Research Grant U54MH084681 and the Intramural Research Program
of the National Center for Advancing Translational Sciences at the
National Institutes of Health.
NR 17
TC 6
Z9 6
U1 0
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
EI 1464-3405
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD JAN 15
PY 2014
VL 24
IS 2
BP 630
EP 635
DI 10.1016/j.bmcl.2013.11.081
PG 6
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 285YI
UT WOS:000329430600044
PM 24360556
ER
PT J
AU Jackson, ER
San Jose, G
Brothers, RC
Edelstein, EK
Sheldon, Z
Haymond, A
Johny, C
Boshoff, HI
Couch, RD
Dowd, CS
AF Jackson, Emily R.
San Jose, Geraldine
Brothers, Robert C.
Edelstein, Emma K.
Sheldon, Zachary
Haymond, Amanda
Johny, Chinchu
Boshoff, Helena I.
Couch, Robin D.
Dowd, Cynthia S.
TI The effect of chain length and unsaturation on Mtb Dxr inhibition and
antitubercular killing activity of FR900098 analogs
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Mycobacterium tuberculosis; Nonmevalonate pathway; Dxr; Antibiotic
ID PHOSPHONIC ACID ANTIBIOTICS; VIVO ANTIMALARIAL ACTIVITY;
1-DEOXY-D-XYLULOSE-5-PHOSPHATE REDUCTOISOMERASE;
MYCOBACTERIUM-TUBERCULOSIS; ESTER PRODRUGS; ANTIBACTERIAL; FOSMIDOMYCIN;
ELIMINATION; FR-31564; PATHWAY
AB Inhibition of the nonmevalonate pathway (NMP) of isoprene biosynthesis has been examined as a source of new antibiotics with novel mechanisms of action. Dxr is the best studied of the NMP enzymes and several reports have described potent Dxr inhibitors. Many of these compounds are structurally related to natural products fosmidomycin and FR900098, each bearing retrohydroxamate and phosphonate groups. We synthesized a series of compounds with two to five methylene units separating these groups to examine what linker length was optimal and tested for inhibition against Mtb Dxr. We synthesized ethyl and pivaloyl esters of these compounds to increase lipophilicity and improve inhibition of Mtb growth. Our results show that propyl or propenyl linker chains are optimal. Propenyl analog 22 has an IC50 of 1.07 mu M against Mtb Dxr. The pivaloyl ester of 22, compound 26, has an MIC of 9.4 mu g/mL, representing a significant improvement in antitubercular potency in this class of compounds. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Jackson, Emily R.; San Jose, Geraldine; Brothers, Robert C.; Edelstein, Emma K.; Sheldon, Zachary; Dowd, Cynthia S.] George Washington Univ, Dept Chem, Washington, DC 20052 USA.
[Haymond, Amanda; Johny, Chinchu; Couch, Robin D.] George Mason Univ, Dept Chem & Biochem, Manassas, VA 20110 USA.
[Haymond, Amanda; Johny, Chinchu; Couch, Robin D.] George Mason Univ, Natl Ctr Biodef & Infect Dis, Manassas, VA 20110 USA.
[Boshoff, Helena I.] NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Dowd, CS (reprint author), George Washington Univ, Dept Chem, 725 21st St NW,Corcoran 107, Washington, DC 20052 USA.
EM cdowd@gwu.edu
FU Intramural Research Program of NIAID/NIH; George Washington University
Department of Chemistry; GWU University Facilitating Fund; NIH
[AI086453]; George Mason University's Department of Chemistry and
Biochemistry; U.S. Army Medical Research and Materiel Command
[W23RYX1291N601]
FX This work was supported by the Intramural Research Program of NIAID/NIH,
the George Washington University Department of Chemistry, the GWU
University Facilitating Fund, and NIH (AI086453 to C. S. D.). R. D. C.
was supported by George Mason University's Department of Chemistry and
Biochemistry and the U.S. Army Medical Research and Materiel Command
W23RYX1291N601.
NR 27
TC 5
Z9 5
U1 2
U2 14
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
EI 1464-3405
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD JAN 15
PY 2014
VL 24
IS 2
BP 649
EP 653
DI 10.1016/j.bmcl.2013.11.067
PG 5
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 285YI
UT WOS:000329430600047
PM 24360562
ER
PT J
AU Weinberger, DM
Grant, LR
Steiner, CA
Weatherholtz, R
Santosham, M
Viboud, C
O'Brien, KL
AF Weinberger, Daniel M.
Grant, Lindsay R.
Steiner, Claudia A.
Weatherholtz, Robert
Santosham, Mathuram
Viboud, Cecile
O'Brien, Katherine L.
TI Seasonal Drivers of Pneumococcal Disease Incidence: Impact of Bacterial
Carriage and Viral Activity
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
DE pneumococcal; co-infections; RSV; seasonality; pneumonia
ID RESPIRATORY-SYNCYTIAL-VIRUS; CONJUGATE VACCINE USE;
STREPTOCOCCUS-PNEUMONIAE; NASOPHARYNGEAL CARRIAGE; UNITED-STATES;
CHILDREN; POPULATION; INFLUENZA; HOSPITALIZATIONS; COLONIZATION
AB Background. Winter-seasonal epidemics of pneumococcal disease provide an opportunity to understand the drivers of incidence. We sought to determine whether seasonality of invasive pneumococcal disease is caused by increased nasopharyngeal transmission of the bacteria or increased susceptibility to invasive infections driven by co-circulating winter respiratory viruses.
Methods. We analyzed pneumococcal carriage and invasive disease data collected from children <7 years old in the Navajo/White Mountain Apache populations between 1996 and 2012. Regression models were used to quantify seasonal variations in carriage prevalence, carriage density, and disease incidence. We also fit a multivariate model to determine the contribution of carriage prevalence and RSV activity to pneumococcal disease incidence while controlling for shared seasonal factors.
Results. The seasonal patterns of invasive pneumococcal disease epidemics varied significantly by clinical presentation: bacteremic pneumococcal pneumonia incidence peaked in late winter, whereas invasive nonpneumonia pneumococcal incidence peaked in autumn. Pneumococcal carriage prevalence and density also varied seasonally, with peak prevalence occurring in late autumn. In a multivariate model, RSV activity was associated with significant increases in bacteremic pneumonia cases (attributable percentage, 15.5%; 95% confidence interval [CI], 1.8%-26.1%) but was not associated with invasive nonpneumonia infections (8.0%; 95% CI, -4.8% to 19.3%). In contrast, seasonal variations in carriage prevalence were associated with significant increases in invasive nonpneumonia infections (31.4%; 95% CI, 8.8%-51.4%) but not with bacteremic pneumonia.
Conclusions. The seasonality of invasive pneumococcal pneumonia could be due to increased susceptibility to invasive infection triggered by viral pathogens, whereas seasonality of other invasive pneumococcal infections might be primarily driven by increased nasopharyngeal transmission of the bacteria.
C1 [Weinberger, Daniel M.] Yale Univ, Sch Publ Hlth, Dept Epidemiol Microbial Dis, New Haven, CT 06520 USA.
[Weinberger, Daniel M.; Viboud, Cecile] NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Grant, Lindsay R.; Weatherholtz, Robert; Santosham, Mathuram; O'Brien, Katherine L.] Ctr Amer Indian Hlth, Baltimore, MD USA.
[O'Brien, Katherine L.] Johns Hopkins Bloomberg Sch Publ Hlth, Int Vaccine Access Ctr, Baltimore, MD USA.
[Steiner, Claudia A.] Agcy Healthcare Res & Qual, Rockville, MD USA.
RP Weinberger, DM (reprint author), Yale Univ, Sch Publ Hlth, Dept Epidemiol Microbial Dis, POB 208034, New Haven, CT 06520 USA.
EM daniel.weinberger@yale.edu
OI Weinberger, Daniel/0000-0003-1178-8086
FU Multinational Influenza Seasonal Mortality Study; Office of Global
Health Affairs' International Influenza Unit in the Office of the
Secretary of the Department of Health and Human Services
FX This work is supported by the Multinational Influenza Seasonal Mortality
Study, with funding from the Office of Global Health Affairs'
International Influenza Unit in the Office of the Secretary of the
Department of Health and Human Services.
NR 31
TC 27
Z9 29
U1 1
U2 10
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 JAN 15
PY 2014
VL 58
IS 2
BP 188
EP 194
DI 10.1093/cid/cit721
PG 7
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 281WI
UT WOS:000329131300009
PM 24190895
ER
PT J
AU Memoli, MJ
Athota, R
Reed, S
Czajkowski, L
Bristol, T
Proudfoot, K
Hagey, R
Voell, J
Fiorentino, C
Ademposi, A
Shoham, S
Taubenberger, JK
AF Memoli, Matthew J.
Athota, Rani
Reed, Susan
Czajkowski, Lindsay
Bristol, Tyler
Proudfoot, Kathleen
Hagey, Rachel
Voell, Jocelyn
Fiorentino, Charles
Ademposi, Angela
Shoham, Shmuel
Taubenberger, Jeffery K.
TI The Natural History of Influenza Infection in the Severely
Immunocompromised vs Nonimmunocompromised Hosts
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
DE influenza A; influenza; immunocompromised host; stem cell transplant
ID HEMATOPOIETIC STEM-CELL; SOLID-ORGAN TRANSPLANT;
IMMUNODEFICIENCY-VIRUS-INFECTION; RAPID SELECTION; H1N1 VIRUS;
RECIPIENTS; PNEUMONIA; MORTALITY; COMMUNITY; THERAPY
AB Introduction. Medical advances have led to an increase in the world's population of immunosuppressed individuals. The most severely immunocompromised patients are those who have been diagnosed with a hematologic malignancy, solid organ tumor, or who have other conditions that require immunosuppressive therapies and/or solid organ or stem cell transplants.
Materials and methods. Medically attended patients with a positive clinical diagnosis of influenza were recruited prospectively and clinically evaluated. Nasal washes and serum were collected. Evaluation of viral shedding, nasal and serum cytokines, clinical illness, and clinical outcomes were performed to compare severely immunocompromised individuals to nonimmunocompromised individuals with influenza infection.
Results. Immunocompromised patients with influenza had more severe disease/complications, longer viral shedding, and more antiviral resistance while demonstrating less clinical symptoms and signs on clinical assessment.
Conclusions. Immunocompromised patients are at risk for more severe or complicated influenza induced disease, which may be difficult to prevent with existing vaccines and antiviral treatments. Specific issues to consider when managing a severely immunocompromised host include the development of asymptomatic shedding, multi-drug resistance during prolonged antiviral therapy, and the potential high risk of pulmonary involvement.
C1 [Memoli, Matthew J.; Athota, Rani; Reed, Susan; Czajkowski, Lindsay; Bristol, Tyler; Proudfoot, Kathleen; Hagey, Rachel; Taubenberger, Jeffery K.] NIAID, Lab Infect Dis, Viral Pathogenesis & Evolut Sect, NIH, Bethesda, MD 20892 USA.
[Voell, Jocelyn; Fiorentino, Charles] NIAID, Div Clin Res, NIH, Bethesda, MD 20892 USA.
[Ademposi, Angela] Medstar Washington Hosp Ctr, Dept Infect Dis, Washington, DC USA.
[Shoham, Shmuel] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
RP Memoli, MJ (reprint author), NIAID, Clin Studies Unit, Viral Pathogenesis & Evolut Sect, Infect Dis Lab,NIH, MSC 3203 33 North Dr, Bethesda, MD 20892 USA.
EM memolim@niaid.nih.gov
OI Hagey, Rachel/0000-0002-4368-3169
FU intramural research program of National Institute of Allergy and
Infectious Diseases
FX This work was supported by the intramural research program of National
Institute of Allergy and Infectious Diseases. Dr Memoli was the lead
scientist for this work leading all aspects including the design,
clinical protocol implementation, laboratory studies, and data
analysis/manuscript preparation.
NR 32
TC 27
Z9 27
U1 1
U2 3
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 JAN 15
PY 2014
VL 58
IS 2
BP 214
EP 224
DI 10.1093/cid/cit725
PG 11
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 281WI
UT WOS:000329131300013
PM 24186906
ER
PT J
AU Birger, RB
Hallett, TB
Sinha, A
Grenfell, BT
Hodder, SL
AF Birger, Ruthie B.
Hallett, Timothy B.
Sinha, Anushua
Grenfell, Bryan T.
Hodder, Sally L.
TI Modeling the Impact of Interventions Along the HIV Continuum of Care in
Newark, New Jersey
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
DE HIV; care continuum; mathematical model
ID UNITED-STATES; ANTIRETROVIRAL THERAPY; INFECTED PATIENTS; TRANSMISSION;
PREVENTION; TREAT; MEN; STRATEGIES; BEHAVIORS; SETTINGS
AB Background. The human immunodeficiency virus (HIV) epidemic in Newark, New Jersey, is among the most severe in the United States. Prevalence ranges up to 3.3% in some groups. The aim of this study is to use a mathematical model of the epidemic in Newark to assess the impact of interventions along the continuum of care, leading to virologic suppression.
Methods. A model was constructed of HIV infection including specific care-continuum steps. The model was calibrated to HIV/AIDS cases in Newark among different populations over a 10-year period. Interventions applied to model fits were increasing proportions tested, linked and retained in care, linked and adherent to treatment, and increasing testing frequency, high-risk-group testing, and adherence. Impacts were assessed by measuring incidence and death reductions 10 years postintervention.
Results. The most effective interventions for reducing incidence were improving treatment adherence and increasing testing frequency and coverage. No single intervention reduced incidence in 2023 by >5%, and the most effective combination of interventions reduced incidence by approximately 16% (2%-24%). The most efficacious interventions for reducing deaths were increasing retention, linkage to care, testing coverage, and adherence. Increasing retention reduced deaths by approximately 27% (24%-29%); the most efficacious combination of interventions reduced deaths in 2023 by approximately 52% (46%-57%).
Conclusions. Reducing HIV deaths in Newark over a 10-year period may be a realizable goal, but reducing incidence is less likely. Our results highlight the importance of addressing leaks across the entire continuum of care and reinforcing efforts to prevention new HIV infections with additional interventions.
C1 [Birger, Ruthie B.; Grenfell, Bryan T.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
[Hallett, Timothy B.] Univ London Imperial Coll Sci Technol & Med, Dept Infect Dis Epidemiol, London SW7 2AZ, England.
[Grenfell, Bryan T.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Birger, RB (reprint author), Princeton Univ, Dept Ecol & Evolutionary Biol, 106A Guyot Hall, Princeton, NJ 08544 USA.
EM rbirger@princeton.edu
RI Birger, Ruthie/F-2416-2014; Barley, Kamal/F-9579-2011
OI Birger, Ruthie/0000-0002-2960-5084; Barley, Kamal/0000-0003-1874-9813
FU New Jersey Health Foundation; Princeton University Department of Ecology
and Evolutionary Biology Fellowship; Bill and Melinda Gates Foundation;
RAPIDD program of the Science and Technology Directorate, US Department
of Homeland Security; Fogarty International Center, National Institutes
of Health; Imperial College
FX The work was supported by a grant from the New Jersey Health Foundation
(formerly University of Medicine and Dentistry Foundation). R. B. B. was
supported by a Princeton University Department of Ecology and
Evolutionary Biology Fellowship. B. T. G. was supported by the Bill and
Melinda Gates Foundation and the RAPIDD program of the Science and
Technology Directorate, US Department of Homeland Security, and the
Fogarty International Center, National Institutes of Health. T. B. H.
was supported by the Bill and Melinda Gates Foundation and Imperial
College.
NR 41
TC 7
Z9 8
U1 0
U2 9
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 JAN 15
PY 2014
VL 58
IS 2
BP 274
EP 284
DI 10.1093/cid/cit687
PG 11
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 281WI
UT WOS:000329131300022
PM 24140971
ER
PT J
AU Williams, JA
Zhang, J
Jeon, H
Nitta, T
Ohigashi, I
Klug, D
Kruhlak, MJ
Choudhury, B
Sharrow, SO
Granger, L
Adams, A
Eckhaus, MA
Jenkinson, SR
Richie, ER
Gress, RE
Takahama, Y
Hodes, RJ
AF Williams, Joy A.
Zhang, Jingjing
Jeon, Hyein
Nitta, Takeshi
Ohigashi, Izumi
Klug, David
Kruhlak, Michael J.
Choudhury, Baishakhi
Sharrow, Susan O.
Granger, Larry
Adams, Anthony
Eckhaus, Michael A.
Jenkinson, S. Rhiannon
Richie, Ellen R.
Gress, Ronald E.
Takahama, Yousuke
Hodes, Richard J.
TI Thymic Medullary Epithelium and Thymocyte Self-Tolerance Require
Cooperation between CD28-CD80/86 and CD40-CD40L Costimulatory Pathways
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID NKT CELL-DEVELOPMENT; MATURE T-CELLS; NEGATIVE SELECTION; AUTOIMMUNE
REGULATOR; CD28 COSTIMULATION; NF-KAPPA-B2 P100; GENE-EXPRESSION;
STROMAL CELLS; CD40 LIGAND; IN-VIVO
AB A critical process during thymic development of the T cell repertoire is the induction of self-tolerance. Tolerance in developing T cells is highly dependent on medullary thymic epithelial cells (mTEC), and mTEC development in turn requires signals from mature single-positive thymocytes, a bidirectional relationship termed thymus crosstalk. We show that CD28-CD80/86 and CD40-CD40L costimulatory interactions, which mediate negative selection and self-tolerance, upregulate expression of LT alpha, LT beta, and receptor activator for NF-kappa B in the thymus and are necessary for medullary development. Combined absence of CD28-CD80/86 and CD40-CD40L results in profound deficiency in mTEC development comparable to that observed in the absence of single-positive thymocytes. This requirement for costimulatory signaling is maintained even in a TCR transgenic model of high-affinity TCR-ligand interactions. CD4 thymocytes maturing in the altered thymic epithelial environment of CD40/CD80/86 knockout mice are highly autoreactive in vitro and are lethal in congenic adoptive transfer in vivo, demonstrating a critical role for these costimulatory pathways in self-tolerance as well as thymic epithelial development. These findings demonstrate that cooperativity between CD28-CD80/86 and CD40-CD40L pathways is required for normal medullary epithelium and for maintenance of self-tolerance in thymocyte development.
C1 [Williams, Joy A.; Zhang, Jingjing; Jeon, Hyein; Klug, David; Kruhlak, Michael J.; Choudhury, Baishakhi; Sharrow, Susan O.; Granger, Larry; Adams, Anthony; Jenkinson, S. Rhiannon; Hodes, Richard J.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Nitta, Takeshi; Ohigashi, Izumi; Takahama, Yousuke] Univ Tokushima, Inst Genome Res, Div Expt Immunol, Tokushima, Japan.
[Eckhaus, Michael A.] NCI, NIH, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA.
[Richie, Ellen R.] Univ Texas MD Anderson Canc Ctr, Dept Carcinogenesis, Sci Pk Res Div, Smithville, TX 78957 USA.
[Gress, Ronald E.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
RP Hodes, RJ (reprint author), NCI, NIH, Bldg 10,Room 4B10,10 Ctr Dr, Bethesda, MD 20892 USA.
EM HodesR@mail.nih.gov
RI Takahama, Yousuke/A-5863-2010
FU Intramural NIH HHS [Z01 BC009281-21, Z01 BC009281-22, ZIA BC009281-24,
ZIA BC009281-26, ZIA BC009281-23, ZIA BC009281-25, ZIA BC009281-27]
NR 54
TC 11
Z9 12
U1 0
U2 7
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 JAN 15
PY 2014
VL 192
IS 2
BP 630
EP 640
DI 10.4049/jimmunol.1302550
PG 11
WC Immunology
SC Immunology
GA 283DA
UT WOS:000329224000009
PM 24337745
ER
PT J
AU Barber, DL
Andrade, BB
McBerry, C
Sereti, I
Sher, A
AF Barber, Daniel L.
Andrade, Bruno B.
McBerry, Cortez
Sereti, Irini
Sher, Alan
TI Role of IL-6 in Mycobacterium avium-Associated Immune Reconstitution
Inflammatory Syndrome
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID CD4(+) T-CELLS; RESTORATION-DISEASE; ANTIRETROVIRAL THERAPY; INFECTED
PATIENTS; HIV-1-INFECTED PATIENTS; CANCER CACHEXIA; TUBERCULOSIS;
INTERLEUKIN-6; GAMMA; MICE
AB Immune reconstitution inflammatory syndrome (IRIS) is a major adverse event of antiretroviral therapy in HIV infection, and paradoxically occurs as HIV viremia is suppressed and CD4 T cell numbers recover. IRIS reflects pathogenic immune responses against opportunistic infections acquired during the period of immunodeficiency, but little is understood about the mechanisms of inflammatory pathology. In this study, we show that IL-6 and C-reactive protein levels transiently rise at the time of the IRIS event in HIV-infected patients, umasking Mycobacterium avium complex infection after starting antiretroviral therapy. To directly test the role of IL-6 in IRIS pathology, we used a model of experimentally inducible IRIS in which M. avium-infected T cell-deficient mice undergo a fatal inflammatory disease after reconstitution with CD4 T cells. We find that IL-6 neutralization reduces C-reactive protein levels, alleviates wasting disease, and extends host survival during experimental IRIS. Moreover, we show that combined blockade of IL-6 and IFN-gamma further reduces IRIS pathology, even after the onset of wasting disease. The combination of these clinical and experimental-model data show that the IL-6 pathway is not only a biomarker of mycobacterial IRIS but also a major mediator of pathology distinct from IFN-gamma and may be a useful target for therapeutic intervention.
C1 [Barber, Daniel L.; McBerry, Cortez] NIAID, T Lymphocyte Biol Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Andrade, Bruno B.; Sher, Alan] NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Sereti, Irini] NIAID, HIV Pathogenesis Unit, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
RP Barber, DL (reprint author), NIAID, NIH, 33 North Dr,Room 1W20B7, Bethesda, MD 20892 USA.
EM barberd@niaid.nih.gov
RI Andrade, Bruno/J-9111-2012
OI Andrade, Bruno/0000-0001-6833-3811
FU National Institutes of Health, National Institute of Allergy and
Infectious Diseases
FX This work was supported by the Intramural Research and Intramural AIDS
Targeted Antiviral programs of the National Institutes of Health,
National Institute of Allergy and Infectious Diseases.
NR 30
TC 13
Z9 13
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 JAN 15
PY 2014
VL 192
IS 2
BP 676
EP 682
DI 10.4049/jimmunol.1301004
PG 7
WC Immunology
SC Immunology
GA 283DA
UT WOS:000329224000014
PM 24337386
ER
PT J
AU Rajagopalan, S
Lee, EC
DuPrie, ML
Long, EO
AF Rajagopalan, Sumati
Lee, Elizabeth C.
DuPrie, Matthew L.
Long, Eric O.
TI TNFR-Associated Factor 6 and TGF-beta-Activated Kinase 1 Control Signals
for a Senescence Response by an Endosomal NK Cell Receptor
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID NATURAL-KILLER-CELLS; KAPPA-B; SECRETORY PHENOTYPE; KIR2DL4 CD158D;
HLA-G; TAK1; PATHWAY; TRAF6; REPRODUCTION; TRANSDUCTION
AB The endosomal innate receptor CD158d (killer cell Ig-like receptor 2DL4) induces cellular senescence in human NK cells in response to soluble ligand (HLA-G or agonist Ab). These senescent NK cells display a senescence-associated secretory phenotype, and their secretome promotes vascular remodeling and angiogenesis. To understand how CD158d initiates signaling for a senescence response, we mapped the region in its cytoplasmic tail that controls signaling. We identified a conserved TNFR-associated factor 6 (TRAF6) binding motif, which was required for CD158d-induced NF-kappa B activation and IL-8 secretion, TRAF6 association with CD158d, and TRAF6 recruitment to CD158d(+) endosomes in transfected cells. The adaptor TRAF6 is known to couple proximal signals from receptors such as endosomal TLRs and CD40 through the kinase TGF-beta-activated kinase 1 (TAK1) for NF-kappa B-dependent proinflammatory responses. Small interfering RNA-mediated silencing of TRAF6 and TAK1, and inhibition of TAK1 blocked CD158d-dependent IL-8 secretion. Stimulation of primary, resting NK cells with soluble Ab to CD158d induced TRAF6 association with CD158d, induced TAK1 phosphorylation, and inhibition of TAK1 blocked the CD158d-dependent reprogramming of NK cells that produces the senescence-associated secretory phenotype signature. Our results reveal that a prototypic TLR and TNFR signaling pathway is used by a killer cell Ig-like receptor that promotes secretion of proinflammatory and proangiogenic mediators as part of a unique senescence phenotype in NK cells.
C1 [Rajagopalan, Sumati; Lee, Elizabeth C.; DuPrie, Matthew L.; Long, Eric O.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
RP Long, EO (reprint author), NIAID, Immunogenet Lab, NIH, Twinbrook 2-201E,12441 Parklawn Dr, Rockville, MD 20852 USA.
EM eLong@nih.gov
RI Long, Eric/G-5475-2011
OI Long, Eric/0000-0002-7793-3728
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 28
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U1 1
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 JAN 15
PY 2014
VL 192
IS 2
BP 714
EP 721
DI 10.4049/jimmunol.1302384
PG 8
WC Immunology
SC Immunology
GA 283DA
UT WOS:000329224000018
PM 24337384
ER
PT J
AU Maier, NK
Crown, D
Liu, J
Leppla, SH
Moayeri, M
AF Maier, Nolan K.
Crown, Devorah
Liu, Jie
Leppla, Stephen H.
Moayeri, Mahtab
TI Arsenic Trioxide and Other Arsenical Compounds Inhibit the NLRP1, NLRP3,
and NAIP5/NLRC4 Inflammasomes
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID ANTHRAX LETHAL TOXIN; ACUTE PROMYELOCYTIC LEUKEMIA; KAPPA-B ACTIVATION;
MULTIPLE-MYELOMA; CANCER-THERAPY; KINASE-KINASE; INFLAMMATION;
CASPASE-1; DISEASE; SUSCEPTIBILITY
AB Inflammasomes are large cytoplasmic multiprotein complexes that activate caspase-1 in response to diverse intracellular danger signals. Inflammasome components termed nucleotide-binding oligomerization domain-like receptor (NLR) proteins act as sensors for pathogen-associated molecular patterns, stress, or danger stimuli. We discovered that arsenicals, including arsenic trioxide and sodium arsenite, inhibited activation of the NLRP1, NLRP3, and NAIP5/NLRC4 inflammasomes by their respective activating signals, anthrax lethal toxin, nigericin, and flagellin. These compounds prevented the autoproteolytic activation of caspase-1 and the processing and secretion of IL-1 beta from macrophages. Inhibition was independent of protein synthesis induction, proteasome-mediated protein breakdown, or kinase signaling pathways. Arsenic trioxide and sodium arsenite did not directly modify or inhibit the activity of preactivated recombinant caspase-1. Rather, they induced a cellular state inhibitory to both the autoproteolytic and substrate cleavage activities of caspase-1, which was reversed by the reactive oxygen species scavenger N-acetylcysteine but not by reducing agents or NO pathway inhibitors. Arsenicals provided protection against NLRP1-dependent anthrax lethal toxin-mediated cell death and prevented NLRP3-dependent neutrophil recruitment in a monosodium urate crystal inflammatory murine peritonitis model. These findings suggest a novel role in inhibition of the innate immune response for arsenical compounds that have been used as therapeutics for a few hundred years.
C1 [Maier, Nolan K.; Crown, Devorah; Leppla, Stephen H.; Moayeri, Mahtab] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Liu, Jie] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA.
RP Moayeri, M (reprint author), Natl Inst Hlth Bldg 33,Room 1W20B, Bethesda, MD 20892 USA.
EM mmoayeri@niaid.nih.gov
OI , /0000-0001-6103-6726
FU National Institute of Allergy and Infectious Diseases
FX This work was supported in part by the Intramural Research Program of
the National Institute of Allergy and Infectious Diseases.
NR 55
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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 JAN 15
PY 2014
VL 192
IS 2
BP 763
EP 770
DI 10.4049/jimmunol.1301434
PG 8
WC Immunology
SC Immunology
GA 283DA
UT WOS:000329224000023
PM 24337744
ER
PT J
AU Adams, KF
Leitzmann, MF
Ballard-Barbash, R
Albanes, D
Harris, TB
Hollenbeck, A
Kipnis, V
AF Adams, Kenneth F.
Leitzmann, Michael F.
Ballard-Barbash, Rachel
Albanes, Demetrius
Harris, Tamara B.
Hollenbeck, Albert
Kipnis, Victor
TI Body Mass and Weight Change in Adults in Relation to Mortality Risk
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE body mass index; body weight; mortality; obesity; weight gain; weight
loss
ID ALL-CAUSE MORTALITY; AGED 40-64 YEARS; FOLLOW-UP; MIDDLE-AGE;
PROSPECTIVE COHORT; US ADULTS; OLD-AGE; INDEX; OVERWEIGHT; MEN
AB Using data from the National Institutes of Health-AARP Diet and Health Study, we evaluated the influence of adulthood weight history on mortality risk. The National Institutes of Health-AARP Diet and Health Study is an observational cohort study of US men and women who were aged 5071 years at entry in 19951996. This analysis focused on 109,947 subjects who had never smoked and were younger than age 70 years. We estimated hazard ratios of total and cause-specific mortality for recalled body mass index (BMI; weight (kg)/height (m)(2)) at ages 18, 35, and 50 years; weight change across 3 adult age intervals; and the effect of first attaining an elevated BMI at 4 successive ages. During 12.5 years follow-up through 2009, 12,017 deaths occurred. BMI at all ages was positively related to mortality. Weight gain was positively related to mortality, with stronger associations for gain between ages 18 and 35 years and ages 35 and 50 years than between ages 50 and 69 years. Mortality risks were higher in persons who attained or exceeded a BMI of 25.0 at a younger age than in persons who reached that threshold later in adulthood, and risks were lowest in persons who maintained a BMI below 25.0. Heavier initial BMI and weight gain in early to middle adulthood strongly predicted mortality risk in persons aged 5069 years.
C1 [Adams, Kenneth F.] HealthPartners Inst Educ & Res, Minneapolis, MN USA.
[Leitzmann, Michael F.] Univ Regensburg, Dept Epidemiol & Prevent Med, Med Ctr, D-93053 Regensburg, Germany.
[Ballard-Barbash, Rachel] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Ballard-Barbash, Rachel] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Albanes, Demetrius] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Kipnis, Victor] NCI, Genet & Biometry Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Hollenbeck, Albert] AARP, Washington, DC USA.
RP Adams, KF (reprint author), Minnesota Canc Surveillance Syst, Minnesota Dept Hlth, 85 East 7th Pl,POB 64882, St Paul, MN 55164 USA.
EM kenneth.adams@state.mn.us
RI Albanes, Demetrius/B-9749-2015
FU National Cancer Institute, National Institutes of Health; National
Institute on Aging, National Institutes of Health
FX This study was supported by the Intramural Research Program of the
National Cancer Institute and the National Institute on Aging, National
Institutes of Health.
NR 47
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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 JAN 15
PY 2014
VL 179
IS 2
BP 135
EP 144
DI 10.1093/aje/kwt254
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 281UV
UT WOS:000329127400002
PM 24173550
ER
PT J
AU Adams, KF
Leitzmann, MF
Ballard-Barbash, R
Albanes, D
Harris, TB
Hollenbeck, A
AF Adams, Kenneth F.
Leitzmann, Michael F.
Ballard-Barbash, Rachel
Albanes, Demetrius
Harris, Tamara B.
Hollenbeck, Albert
TI Adams et al. Respond to Body Mass Index and Mortality
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Editorial Material
ID ASSOCIATION; OVERWEIGHT; OBESITY
C1 [Adams, Kenneth F.] HealthPartners Inst Educ & Res, Minneapolis, MN USA.
[Leitzmann, Michael F.] Univ Regensburg, Dept Epidemiol & Prevent Med, Med Ctr, D-93053 Regensburg, Germany.
[Ballard-Barbash, Rachel] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Ballard-Barbash, Rachel] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Albanes, Demetrius] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Hollenbeck, Albert] AARP, Washington, DC USA.
RP Adams, KF (reprint author), Minnesota Canc Surveillance Syst, Minnesota Dept Hlth, 85 East 7th Pl,POB 64882, St Paul, MN 55164 USA.
EM kenneth.adams@state.mn.us
RI Albanes, Demetrius/B-9749-2015
NR 5
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U1 0
U2 1
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 JAN 15
PY 2014
VL 179
IS 2
BP 147
EP 148
DI 10.1093/aje/kwt253
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 281UV
UT WOS:000329127400004
ER
PT J
AU Quandelacy, TM
Viboud, C
Charu, V
Lipsitch, M
Goldstein, E
AF Quandelacy, Talia M.
Viboud, Cecile
Charu, Vivek
Lipsitch, Marc
Goldstein, Edward
TI Age- and Sex-related Risk Factors for Influenza-associated Mortality in
the United States Between 19972007
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE age; influenza; mortality; sex; underlying cause
ID INVASIVE PNEUMOCOCCAL DISEASE; RESPIRATORY SYNCYTIAL VIRUS; ACUTE
MYOCARDIAL-INFARCTION; CONJUGATE VACCINE; OLDER-ADULTS; HONG-KONG;
DEATHS; INFECTION; ENGLAND; SERIES
AB Limited information on age- and sex-specific estimates of influenza-associated death with different underlying causes is currently available. We regressed weekly age- and sex-specific US mortality outcomes underlying several causes between 1997 and 2007 to incidence proxies for influenza A/H3N2, A/H1N1, and B that combine data on influenzalike illness consultations and respiratory specimen testing, adjusting for seasonal baselines and time trends. Adults older than 75 years of age had the highest average annual rate of influenza-associated mortality, with 141.15 deaths per 100,000 people (95 confidence interval (CI): 118.3, 163.9), whereas children under 18 had the lowest average mortality rate, with 0.41 deaths per 100,000 people (95 CI: 0.23, 0.60). In addition to respiratory and circulatory causes, mortality with underlying cancer, diabetes, renal disease, and Alzheimer disease had a contribution from influenza in adult age groups, whereas mortality with underlying septicemia had a contribution from influenza in children. For adults, within several age groups and for several underlying causes, the rate of influenza-associated mortality was somewhat higher in men than in women. Of note, in men 5064 years of age, our estimate for the average annual rate of influenza-associated cancer mortality per 100,000 persons (1.90, 95 CI: 1.20, 2.62) is similar to the corresponding rate of influenza-associated respiratory deaths (1.81, 95 CI: 1.42, 2.21). Age, sex, and underlying health conditions should be considered when planning influenza vaccination and treatment strategies.
C1 [Quandelacy, Talia M.; Lipsitch, Marc; Goldstein, Edward] Harvard Univ, Dept Epidemiol, Ctr Communicable Dis Dynam, Sch Publ Hlth, Boston, MA 02115 USA.
[Viboud, Cecile; Charu, Vivek] NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Charu, Vivek] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Lipsitch, Marc] Harvard Univ, Dept Immunol & Infect Dis, Sch Publ Hlth, Boston, MA 02115 USA.
RP Goldstein, E (reprint author), Harvard Univ, Dept Epidemiol, Ctr Communicable Dis Dynam, Sch Publ Hlth, 677 Huntington Ave,Kresge Room 506, Boston, MA 02115 USA.
EM egoldste@hsph.harvard.edu
OI Lipsitch, Marc/0000-0003-1504-9213
FU National Institute of General Medical Sciences [U54GM088558]; US
National Institutes of Health [1K01AI101010-01]; Fogarty International
Center, National Institutes of Health
FX This work was supported in part by award number U54GM088558 from the
National Institute of General Medical Sciences (Talia M. Quandelacy,
Marc Lipsitch, and Edward Goldstein), by the US National Institutes of
Health K01 award 1K01AI101010-01 (Edward Goldstein), and by the
influenza research program of the Fogarty International Center, National
Institutes of Health (Cecile Viboud, Vivek Charu).
NR 38
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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 JAN 15
PY 2014
VL 179
IS 2
BP 156
EP 167
DI 10.1093/aje/kwt235
PG 12
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 281UV
UT WOS:000329127400006
PM 24190951
ER
PT J
AU Pulliam, JRC
Dushoff, J
AF Pulliam, Juliet R. C.
Dushoff, Jonathan
TI Re: The Case-Chaos Study l Adjunct or Alternative to Conventional
Case-Control Study Methodology
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Letter
C1 [Pulliam, Juliet R. C.] Univ Florida, Dept Biol, Coll Liberal Arts & Sci, Gainesville, FL 32611 USA.
[Pulliam, Juliet R. C.] Univ Florida, Emerging Pathogens Inst, Gainesville, FL 32610 USA.
[Pulliam, Juliet R. C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Dushoff, Jonathan] McMaster Univ, Dept Biol, Fac Sci, Hamilton, ON L8S 4K1, Canada.
RP Pulliam, JRC (reprint author), Univ Florida, Dept Biol, Coll Liberal Arts & Sci, Gainesville, FL 32611 USA.
EM pulliam@ufl.edu
OI Pulliam, Juliet/0000-0003-3314-8223
FU Canadian Institutes of Health Research
NR 6
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U1 0
U2 0
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 JAN 15
PY 2014
VL 179
IS 2
BP 261
EP 262
DI 10.1093/aje/kwt242
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 281UV
UT WOS:000329127400018
PM 24125919
ER
PT J
AU Wang, YC
Yang, JS
Johnston, R
Ren, QZ
Lee, YJ
Luan, HJ
Brody, T
Odenwald, WF
Lee, T
AF Wang, Yu-Chun
Yang, Jacob S.
Johnston, Rebecca
Ren, Qingzhong
Lee, Ying-Jou
Luan, Haojiang
Brody, Thomas
Odenwald, Ward F.
Lee, Tzumin
TI Drosophila intermediate neural progenitors produce lineage-dependent
related series of diverse neurons
SO DEVELOPMENT
LA English
DT Article
DE Drosophila type II neuroblasts; Adult brain; Cell lineage analysis;
Intermediate neural progenitors; Neuronal cell fate; Temporal identity
ID AMPLIFYING NEUROBLAST LINEAGES; BRAIN-DEVELOPMENT; CENTRAL COMPLEX;
CEREBRAL-CORTEX; GLIAL-CELLS; SPECIFICATION; ORIGIN
AB Drosophila type II neuroblasts (NBs), like mammalian neural stem cells, deposit neurons through intermediate neural progenitors (INPs) that can each produce a series of neurons. Both type II NBs and INPs exhibit age-dependent expression of various transcription factors, potentially specifying an array of diverse neurons by combinatorial temporal patterning. Not knowing which mature neurons are made by specific INPs, however, conceals the actual variety of neuron types and limits further molecular studies. Here we mapped neurons derived from specific type II NB lineages and found that sibling INPs produced a morphologically similar but temporally regulated series of distinct neuron types. This suggests a common fate diversification program operating within each INP that is modulated by NB age to generate slightly different sets of diverse neurons based on the INP birth order. Analogous mechanisms might underlie the expansion of neuron diversity via INPs in mammalian brain.
C1 [Wang, Yu-Chun; Yang, Jacob S.; Johnston, Rebecca; Ren, Qingzhong; Lee, Ying-Jou; Luan, Haojiang; Lee, Tzumin] Howard Hughes Med Inst, Ashburn, VA 20147 USA.
[Brody, Thomas; Odenwald, Ward F.] NINDS, Neural Cell Fate Determinants Sect, NIH, Bethesda, MD 20892 USA.
RP Lee, T (reprint author), Howard Hughes Med Inst, Janelia Farm Res Campus,19700 Helix Dr, Ashburn, VA 20147 USA.
EM leet@janelia.hhmi.org
RI Yang, Shun-Jen/G-2968-2015; Ren, Qingzhong/H-8064-2016;
OI Ren, Qingzhong/0000-0001-9633-1477
FU Howard Hughes Medical Institute; National Institutes of Health
FX This work was supported by Howard Hughes Medical Institute and National
Institutes of Health. Deposited in PMC for release after 6 months.
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PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0950-1991
EI 1477-9129
J9 DEVELOPMENT
JI Development
PD JAN 15
PY 2014
VL 141
IS 2
BP 253
EP 258
DI 10.1242/dev.103069
PG 6
WC Developmental Biology
SC Developmental Biology
GA 282JI
UT WOS:000329166700003
PM 24306106
ER
PT J
AU Sulkowski, M
Kim, YJ
Serpe, M
AF Sulkowski, Mikolaj
Kim, Young-Jun
Serpe, Mihaela
TI Postsynaptic glutamate receptors regulate local BMP signaling at the
Drosophila neuromuscular junction
SO DEVELOPMENT
LA English
DT Article
DE BMP signaling; Glutamatergic synapses; Glutamate receptor; Drosophila;
Neuromuscular junction
ID PRESYNAPTIC TRANSMITTER RELEASE; SYNAPTIC GROWTH; RETROGRADE SIGNAL;
PROTEIN-KINASE; NEUROTRANSMITTER RELEASE; MORPHOGEN GRADIENTS;
GENETIC-ANALYSIS; QUANTAL SIZE; II RECEPTOR; HOMOLOG GBB
AB Effective communication between pre- and postsynaptic compartments is required for proper synapse development and function. At the Drosophila neuromuscular junction (NMJ), a retrograde BMP signal functions to promote synapse growth, stability and homeostasis and coordinates the growth of synaptic structures. Retrograde BMP signaling triggers accumulation of the pathway effector pMad in motoneuron nuclei and at synaptic termini. Nuclear pMad, in conjunction with transcription factors, modulates the expression of target genes and instructs synaptic growth; a role for synaptic pMad remains to be determined. Here, we report that pMad signals are selectively lost at NMJ synapses with reduced postsynaptic sensitivities. Despite this loss of synaptic pMad, nuclear pMad persisted in motoneuron nuclei, and expression of BMP target genes was unaffected, indicating a specific impairment in pMad production/maintenance at synaptic termini. During development, synaptic pMad accumulation followed the arrival and clustering of ionotropic glutamate receptors (iGluRs) at NMJ synapses. Synaptic pMad was lost at NMJ synapses developing at suboptimal levels of iGluRs and Neto, an auxiliary subunit required for functional iGluRs. Genetic manipulations of non-essential iGluR subunits revealed that synaptic pMad signals specifically correlated with the postsynaptic type-A glutamate receptors. Altering type-A receptor activities via protein kinase A (PKA) revealed that synaptic pMad depends on the activity and not the net levels of postsynaptic type-A receptors. Thus, synaptic pMad functions as a local sensor for NMJ synapse activity and has the potential to coordinate synaptic activity with a BMP retrograde signal required for synapse growth and homeostasis.
C1 [Sulkowski, Mikolaj; Kim, Young-Jun; Serpe, Mihaela] NICHD, Program Cellular Regulat & Metab, NIH, Bethesda, MD 20892 USA.
RP Serpe, M (reprint author), NICHD, Program Cellular Regulat & Metab, NIH, Bethesda, MD 20892 USA.
EM mihaela.serpe@nih.gov
FU National Institutes of Health, National Institute of Child Health and
Human Development [Z01 HD008869, Z01 HD008914]
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Child Health and
Human Development [grants Z01 HD008869 and Z01 HD008914]. Deposited in
PMC for release after 12 months.
NR 77
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U2 8
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PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0950-1991
EI 1477-9129
J9 DEVELOPMENT
JI Development
PD JAN 15
PY 2014
VL 141
IS 2
BP 436
EP 447
DI 10.1242/dev.097758
PG 12
WC Developmental Biology
SC Developmental Biology
GA 282JI
UT WOS:000329166700020
PM 24353060
ER
PT J
AU Salie, M
van der Merwe, L
Moller, M
Daya, M
van der Spuy, GD
van Helden, PD
Martin, MP
Gao, XJ
Warren, RM
Carrington, M
Hoal, EG
AF Salie, Muneeb
van der Merwe, Lize
Moeller, Marlo
Daya, Michelle
van der Spuy, Gian D.
van Helden, Paul D.
Martin, Maureen P.
Gao, Xiao-jiang
Warren, Robin M.
Carrington, Mary
Hoal, Eileen G.
TI Associations Between Human Leukocyte Antigen Class I Variants and the
Mycobacterium tuberculosis Subtypes Causing Disease
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE Mycobacterium tuberculosis; tuberculosis; human leukocyte antigens;
host-pathogen; coadaptation; susceptibility
ID SINGLE-NUCLEOTIDE POLYMORPHISMS; CD8(+) T-CELLS; BEIJING GENOTYPE;
HLA-C; SUSCEPTIBILITY; DIVERSITY; ORIGIN; IDENTIFICATION; PATHOGENESIS;
POPULATIONS
AB Background. The development of active tuberculosis disease has been shown to be multifactorial. Interactions between host and bacterial genotype may influence disease outcome, with some studies indicating the adaptation of M. tuberculosis strains to specific human populations. Here we investigate the role of the human leukocyte antigen (HLA) class I genes in this biological process.
Methods. Three hundred patients with tuberculosis from South Africa were typed for their HLA class I alleles by direct sequencing. Mycobacterium tuberculosis genotype classification was done by IS6110 restriction fragment length polymorphism genotyping and spoligotyping.
Results. We showed that Beijing strain occurred more frequently in individuals with multiple disease episodes (P < .001) with the HLA-B27 allele lowering the odds of having an additional episode (odds ratio, 0.21; P = .006). Associations were also identified for specific HLA types and disease caused by the Beijing, LAM, LCC, and Quebec strains. HLA types were also associated with disease caused by strains from the Euro-American or East Asian lineages, and the frequencies of these alleles in their sympatric human populations identified potential coevolutionary events between host and pathogen.
Conclusions. This is the first report of the association of human HLA types and M. tuberculosis strain genotype, highlighting that both host and pathogen genetics need to be taken into consideration when studying tuberculosis disease development.
C1 [Salie, Muneeb; van der Merwe, Lize; Moeller, Marlo; Daya, Michelle; van der Spuy, Gian D.; van Helden, Paul D.; Warren, Robin M.; Hoal, Eileen G.] Univ Stellenbosch, MRC Ctr Mol & Cellular Biol, ZA-7505 Tygerberg, South Africa.
[Salie, Muneeb; van der Merwe, Lize; Moeller, Marlo; Daya, Michelle; van der Spuy, Gian D.; van Helden, Paul D.; Warren, Robin M.; Hoal, Eileen G.] Univ Stellenbosch, Div Mol Biol & Human Genet, DST NRF Ctr Excellence Biomed TB Res, ZA-7505 Tygerberg, South Africa.
[van der Merwe, Lize] MRC, MRC Biostat Unit, Tygerberg, South Africa.
[van der Merwe, Lize] Univ Western Cape, Dept Stat, ZA-7535 Bellville, South Africa.
[Martin, Maureen P.; Gao, Xiao-jiang; Carrington, Mary] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD USA.
[Martin, Maureen P.; Gao, Xiao-jiang; Carrington, Mary] MIT, Ragon Inst Massachusetts Gen Hosp, Cambridge, MA 02139 USA.
[Martin, Maureen P.; Gao, Xiao-jiang; Carrington, Mary] Harvard Univ, Cambridge, MA 02138 USA.
RP Hoal, EG (reprint author), Univ Stellenbosch, Fac Med & Hlth Sci, Francie van Zijl Dr,Fisan Bldg,4th Floor,Room F41, ZA-7505 Tygerberg, South Africa.
EM egvh@sun.ac.za
OI Hoal, Eileen/0000-0002-6444-5688; Salie, Muneeb/0000-0002-7980-0048;
Moller, Marlo/0000-0002-0805-6741
FU Wellcome Trust [053844/Z/98/Z]; Frederick National Laboratory for Cancer
Research [HHSN261200800001E]; NIH, Frederick National Lab, Center for
Cancer Research; Harry Crossley Foundation; National Research Foundation
(DAAD-NRF); Columbia University-Southern African Fogarty AIDS
International Training and Research Program through the Fogarty
International Center, National Institutes of Health [2 D43 TW000231 16]
FX This work was supported by the Wellcome Trust (053844/Z/98/Z to P. D.
vH. and E. G. H.); Frederick National Laboratory for Cancer Research
(contract number HHSN261200800001E); the Intramural Research Program of
the NIH, Frederick National Lab, Center for Cancer Research; the Harry
Crossley Foundation; the National Research Foundation (DAAD-NRF); and
the Columbia University-Southern African Fogarty AIDS International
Training and Research Program through the Fogarty International Center,
National Institutes of Health (grant number 2 D43 TW000231 16 to M. S.).
NR 50
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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 JAN 15
PY 2014
VL 209
IS 2
BP 216
EP 223
DI 10.1093/infdis/jit443
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 282GA
UT WOS:000329157200010
PM 23945374
ER
PT J
AU Redford, PS
Mayer-Barber, KD
McNab, FW
Stavropoulos, E
Wack, A
Sher, A
O'Garra, A
AF Redford, Paul S.
Mayer-Barber, Katrin D.
McNab, Finlay W.
Stavropoulos, Evangelos
Wack, Andreas
Sher, Alan
O'Garra, Anne
TI Influenza A Virus Impairs Control of Mycobacterium tuberculosis
Coinfection Through a Type I Interferon Receptor-Dependent Pathway
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE Mycobacterium tuberculosis; tuberculosis; influenza; Interferon; type I
IFN; co-infection
ID INFECTION; SUSCEPTIBILITY; PNEUMONIA; INDUCTION; MICE
AB Influenza followed by severe acute bacterial pneumonia is a major cause of mortality worldwide. Several mechanisms account for this enhanced susceptibility, including increased production of type I interferon (IFN). In individuals infected with Mycobacterium tuberculosis, the influence of acute viral infections on tuberculosis progression is unclear. We show that prior exposure of mice to influenza A virus, followed by M. tuberculosis infection, leads to enhanced mycobacterial growth and decreased survival. Following M. tuberculosis/influenza virus coinfection, mycobacterial growth is enhanced by a type I IFN signaling pathway. Our findings highlight the detrimental influence influenza virus infection can have before or during M. tuberculosis infection.
C1 [Redford, Paul S.; McNab, Finlay W.; Stavropoulos, Evangelos; Wack, Andreas; O'Garra, Anne] Natl Inst Med Res, MRC, Div Immunoregulat, London NW7 1AA, England.
[O'Garra, Anne] Univ London Imperial Coll Sci Technol & Med, NHLI, Div Med, London W2 1PG, England.
[Mayer-Barber, Katrin D.; Sher, Alan] NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP O'Garra, A (reprint author), Natl Inst Med Res, MRC, Div Immunoregulat, Mill Hill, London NW7 1AA, England.
EM aogarra@nimr.mrc.ac.uk
OI Wack, Andreas/0000-0001-5226-2991; O'Garra, Anne/0000-0001-9845-6134
FU Medical Research Council, United Kingdom [U117565642, U117597139];
European Research Council [ERC-2011-AdG 294682-TB-PATH]; National
Institute of Allergy and Infectious Diseases, National Institutes of
Health
FX This work was supported by the Medical Research Council, United Kingdom
(grant U117565642: P. S. R., F. W. M., E. S., and A. O. and grant
U117597139: A. W.), the European Research Council (grant ERC-2011-AdG
294682-TB-PATH: P. S. R., F. W. M., E. S., and A. O.), and the
Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health (K. D. M.-B. and A.
S.).
NR 15
TC 23
Z9 23
U1 1
U2 4
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD JAN 15
PY 2014
VL 209
IS 2
BP 270
EP 274
DI 10.1093/infdis/jit424
PG 5
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 282GA
UT WOS:000329157200017
PM 23935205
ER
PT J
AU Ojo, KK
Eastman, RT
Vidadala, R
Zhang, ZS
Rivas, KL
Choi, R
Lutz, JD
Reid, MC
Fox, AMW
Hulverson, MA
Kennedy, M
Isoherranen, N
Kim, LM
Comess, KM
Kempf, DJ
Verlinde, CLMJ
Su, XZ
Kappe, SHI
Maly, DJ
Fan, EK
Van Voorhis, WC
AF Ojo, Kayode K.
Eastman, Richard T.
Vidadala, RamaSubbaRao
Zhang, Zhongsheng
Rivas, Kasey L.
Choi, Ryan
Lutz, Justin D.
Reid, Molly C.
Fox, Anna M. W.
Hulverson, Matthew A.
Kennedy, Mark
Isoherranen, Nina
Kim, Laura M.
Comess, Kenneth M.
Kempf, Dale J.
Verlinde, Christophe L. M. J.
Su, Xin-zhuan
Kappe, Stefan H. I.
Maly, Dustin J.
Fan, Erkang
Van Voorhis, Wesley C.
TI A Specific Inhibitor of PfCDPK4 Blocks Malaria Transmission:
Chemical-genetic Validation
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE Plasmodium falciparum; malaria transmission-blocking; calcium-dependent
protein kinase 4; bumped kinase inhibitors
ID PROTEIN-KINASE 1; PLASMODIUM-FALCIPARUM; CALCIUM; PARASITES; GONDII;
POTENT; EXPRESSION; RESISTANCE; PRIMAQUINE; MOSQUITOS
AB Malaria parasites are transmitted by mosquitoes, and blocking parasite transmission is critical in reducing or eliminating malaria in endemic regions. Here, we report the pharmacological characterization of a new class of malaria transmission-blocking compounds that acts via the inhibition of Plasmodia CDPK4 enzyme. We demonstrate that these compounds achieved selectivity over mammalian kinases by capitalizing on a small serine gatekeeper residue in the active site of the Plasmodium CDPK4 enzyme. To directly confirm the mechanism of action of these compounds, we generated P. falciparum parasites that express a drug-resistant methionine gatekeeper (S147M) CDPK4 mutant. Mutant parasites showed a shift in exflagellation EC50 relative to the wild-type strains in the presence of compound 1294, providing chemical-genetic evidence that CDPK4 is the target of the compound. Pharmacokinetic analyses suggest that coformulation of this transmission-blocking agent with asexual stage antimalarials such as artemisinin combination therapy (ACT) is a promising option for drug delivery that may reduce transmission of malaria including drug-resistant strains. Ongoing studies include refining the compounds to improve efficacy and toxicological properties for efficient blocking of malaria transmission.
C1 [Ojo, Kayode K.; Rivas, Kasey L.; Choi, Ryan; Reid, Molly C.; Fox, Anna M. W.; Hulverson, Matthew A.; Van Voorhis, Wesley C.] Univ Washington, Dept Med, Div Allergy & Infect Dis, Seattle, WA 98195 USA.
[Eastman, Richard T.; Su, Xin-zhuan] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
[Vidadala, RamaSubbaRao; Maly, Dustin J.] Univ Washington, Dept Chem, Seattle, WA 98195 USA.
[Zhang, Zhongsheng; Verlinde, Christophe L. M. J.; Fan, Erkang] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
[Lutz, Justin D.; Isoherranen, Nina; Kappe, Stefan H. I.] Univ Washington, Dept Pharmaceut, Seattle, WA 98195 USA.
[Kennedy, Mark] Seattle Biomed Res Inst, Washington, DC USA.
[Kim, Laura M.; Comess, Kenneth M.; Kempf, Dale J.] AbbVie, Global Pharmaceut R&D, N Chicago, IL USA.
RP Van Voorhis, WC (reprint author), Univ Washington, Dept Med, Div Allergy & Infect Dis, CERID, MS 358061,750 Republican St,E-606, Seattle, WA 98195 USA.
EM wesley@uw.edu
OI Su, Xinzhuan/0000-0003-3246-3248
FU National Institute of Allergy and Infectious Diseases (NIAID) of the
National Institutes of Health (NIH) [R01AI089441, R01AI080625]; NIH
[R01GM086858, 1 R01 AI089441, 5 R01 AI080625]; Divisions of Intramural
Research at the National Institute of Allergy and Infectious Diseases,
National Institutes of Health
FX Research reported in this publication was supported by National
Institute of Allergy and Infectious Diseases (NIAID) of the National
Institutes of Health (NIH) under award number R01AI089441, R01AI080625,
and NIH grant R01GM086858. Work in the Van Voorhis lab was supported by
NIH grants 1 R01 AI089441 and 5 R01 AI080625. Richard Eastman and
Xin-zhuan Su were supported by the Divisions of Intramural Research at
the National Institute of Allergy and Infectious Diseases, National
Institutes of Health. The Maly Lab was supported by NIH grant
R01GM086858.
NR 29
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Z9 20
U1 1
U2 18
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 JAN 15
PY 2014
VL 209
IS 2
BP 275
EP 284
DI 10.1093/infdis/jit522
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 282GA
UT WOS:000329157200018
PM 24123773
ER
PT J
AU Gautam, S
Kumar, R
Singh, N
Singh, AK
Rai, M
Sacks, D
Sundar, S
Nylen, S
AF Gautam, Shalini
Kumar, Rajiv
Singh, Neetu
Singh, Abhishek Kumar
Rai, Madhukar
Sacks, David
Sundar, Shyam
Nylen, Susanne
TI CD8 T Cell Exhaustion in Human Visceral Leishmaniasis
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE Visceral leishmaniasis; CD8 T cell; IL-10; PD1; CTLA-4; spleen; PBMC
ID AZAR DERMAL LEISHMANIASIS; KALA-AZAR; CUTANEOUS LEISHMANIASIS;
INHIBITORY RECEPTORS; DISEASE PROGRESSION; DONOVANI INFECTION;
INTERFERON-GAMMA; LYMPHOCYTES; EXPRESSION; CYTOTOXICITY
AB Little is known about CD8 T cells in human visceral leishmaniasis (VL) and it is unclear if these cells have a protective, pathological and/or suppressive function. In experimental VL CD8 T cells have been shown to contribute to parasite control and play an important role in vaccine-generated immunity. To better understand the role of CD8 T cells in human VL, we examined molecules associated with anergy and cytotoxic T lymphocytes (CTL) in peripheral blood mononuclear cells (PBMC) and splenic aspirates (SA), and in CD8 cells derived from these tissues. Gene and surface marker expression suggest that splenic CD8 cell predominantly display an anergic phenotype, whereas CD8-PBMC have features of both anergic cells and CTLs. CD8 cells contribute to the baseline IFN gamma levels in whole blood (WB) and SA cultures, but not to the Leishmania induced IFN gamma release that is revealed using WB cultures. Blockade of CTLA-4 or PD1 had no effect on IFN gamma production or parasite survival in SA cultures. Following cure, CD8 T cells contribute to the Leishmania induced IFN gamma production observed in Leishmania stimulated cell cultures. We suggest CD8 T cells are driven to anergy/exhaustion in human VL, which affect their ability to contribute to protective immune responses.
C1 [Gautam, Shalini; Kumar, Rajiv; Singh, Neetu; Singh, Abhishek Kumar; Rai, Madhukar; Sundar, Shyam] Banaras Hindu Univ, Inst Med Sci, Varanasi 221005, Uttar Pradesh, India.
[Sacks, David] NIAID, NIH, Bethesda, MD 20892 USA.
[Nylen, Susanne] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, S-17177 Stockholm, Sweden.
RP Nylen, S (reprint author), Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, Box 280, S-17177 Stockholm, Sweden.
EM susanne.nylen@ki.se
OI Nylen, Susanne/0000-0002-3875-3353; Kumar, Rajiv/0000-0003-2338-1494
FU Extramural Research Program of the National Institute of Allergy
(NIAID), National Institutes of Health (NIH) Tropical Medicine Research
Centers [P50 AI074321]; Indian Council of Medical Research; Swedish
Society of Medicine [SLS98351]; NIAID/NIH Intramural Research Program
FX This work was supported by the Extramural Research Program of the
National Institute of Allergy (NIAID), National Institutes of Health
(NIH) Tropical Medicine Research Centers [P50 AI074321]; the Indian
Council of Medical Research; the Swedish Society of Medicine [SLS98351]
and NIAID/NIH Intramural Research Program.
NR 35
TC 31
Z9 31
U1 2
U2 6
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD JAN 15
PY 2014
VL 209
IS 2
BP 290
EP 299
DI 10.1093/infdis/jit401
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 282GA
UT WOS:000329157200020
PM 23922369
ER
PT J
AU Burke, JF
Long, NM
Zaghloul, KA
Sharan, AD
Sperling, MR
Kahana, MJ
AF Burke, John F.
Long, Nicole M.
Zaghloul, Kareem A.
Sharan, Ashwini D.
Sperling, Michael R.
Kahana, Michael J.
TI Human intracranial high-frequency activity maps episodic memory
formation in space and time
SO NEUROIMAGE
LA English
DT Article
DE Electrocorticography; Memory; Gamma; Functional mapping
ID ELECTROCORTICOGRAPHIC SPECTRAL-ANALYSIS; HUMAN SENSORIMOTOR CORTEX;
LOCAL-FIELD POTENTIALS; BOLD-FMRI; PREFRONTAL CORTEX; NEURAL ACTIVITY;
GAMMA ACTIVITY; SUBSEQUENT MEMORY; SIGNAL; POWER
AB Noninvasive neuroimaging studies have revealed a network of brain regions that activate during human memory encoding; however, the relative timing of such activations remains unknown. Here we used intracranially recorded high-frequency activity (HFA) to first identify regions that activate during successful encoding. Then, we leveraged the high-temporal precision of HFA to investigate the timing of such activations. We found that memory encoding invokes two spatiotemporally distinct activations: early increases in HFA that involve the ventral visual pathway as well as the medial temporal lobe and late increases in HFA that involve the left inferior frontal gyrus, left posterior parietal cortex, and left ventrolateral temporal cortex. We speculate that these activations reflect higher-order visual processing and top-down modulation of attention/semantic information, respectively. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Burke, John F.] Univ Penn, Neurosci Grad Grp, Philadelphia, PA 19104 USA.
[Long, Nicole M.; Kahana, Michael J.] Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA.
[Zaghloul, Kareem A.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Sharan, Ashwini D.] Thomas Jefferson Univ Hosp, Dept Neurol Surg, Philadelphia, PA 19107 USA.
[Sperling, Michael R.] Thomas Jefferson Univ Hosp, Dept Neurol, Philadelphia, PA 19107 USA.
RP Burke, JF (reprint author), Univ Penn, Neurosci Grad Grp, 3401 Walnut St,Room 303C, Philadelphia, PA 19104 USA.
EM jfburke@med.upenn.edu
FU National Institutes of Health [MH055687, MH061975, NS067316, MH017168];
Dana Foundation
FX This work was supported by the National Institutes of Health grants
MH055687, MH061975, NS067316, and MH017168 and the Dana Foundation. We
thank Dale H. Wyeth and Edmund Wyeth for technical assistance at Thomas
Jefferson Hospital; Ashwin G. Ramayya and Ryan B. Williams for helpful
discussion and input. The authors declare no competing financial
interests. We are indebted to all patients who have selflessly
volunteered their time to participate in our study.
NR 59
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U1 0
U2 8
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD JAN 15
PY 2014
VL 85
SI SI
BP 834
EP 843
DI 10.1016/j.neuroimage.2013.06.067
PN 2
PG 10
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 278DX
UT WOS:000328870400021
PM 23827329
ER
PT J
AU Burbach, JPH
Grant, P
Hellemons, AJCGM
DeGiorgis, JA
Li, KW
Pant, HC
AF Burbach, J. Peter H.
Grant, Philip
Hellemons, Anita J. C. G. M.
DeGiorgis, Joseph A.
Li, Ka Wan
Pant, Harish C.
TI Differential expression of the FMRF gene in adult and hatchling stellate
ganglia of the squid Loligo pealei
SO BIOLOGY OPEN
LA English
DT Article
DE FMRFamide; Cephalopods; Mollusk; Stellate ganglion; Giant axon;
Prohormone processing
ID FMRFAMIDE-RELATED PEPTIDES; CUTTLEFISH SEPIA-OFFICINALIS;
CENTRAL-NERVOUS-SYSTEM; OCTOPUS-VULGARIS; NEUROPEPTIDERGIC CONTROL;
CAENORHABDITIS-ELEGANS; IDIOSEPIUS-NOTOIDES; CEPHALOPOD MOLLUSK;
MOLECULAR ANALYSIS; RFAMIDE PEPTIDES
AB The giant fiber system of the squid Loligo pealei mediates the escape response and is an important neurobiological model. Here, we identified an abundant transcript in the stellate ganglion (SG) that encodes a FMRFamide precursor, and characterized FMRFamide and FI/LRF-amide peptides. To determine whether FMRFamide plays a role in the adult and hatchling giant fiber system, we studied the expression of the Fmrf gene and FMRFamide peptides. In stage 29 embryos and stage 30 hatchlings, Ffmr transcripts and FMRFamide peptide were low to undetectable in the SG, in contrast to groups of neurons intensely expressing the Fmrf gene in several brain lobes, including those that innervate the SG. In the adult SG the Fmrf gene was highly expressed, but the FMRFamide peptide was in low abundance. Intense staining for FMRFamide in the adult SG was confined to microneurons and fibers in the neuropil and to small fibers surrounding giant axons in stellar nerves. This shows that the Fmrf gene in the SG is strongly regulated post-hatching, and suggests that the FMRFamide precursor is incompletely processed in the adult SG. The data suggest that the SG only employs the Fmrf gene post-hatching and restricts the biosynthesis of FMRFamide, demonstrating that this peptide is not a major transmitter of the giant fiber system. This contrasts with brain lobes that engage FMRFamide embryonically as a regulatory peptide in multiple neuronal systems, including the afferent fibers that innervate the SG. The biological significance of these mechanisms may be to generate diversity within Fmrf-expressing systems in cephalopods. (C) 2013. Published by The Company of Biologists Ltd.
C1 [Burbach, J. Peter H.; Hellemons, Anita J. C. G. M.] Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Translat Neurosci, NL-3584 CG Utrecht, Netherlands.
[Burbach, J. Peter H.; Grant, Philip; Hellemons, Anita J. C. G. M.; DeGiorgis, Joseph A.; Pant, Harish C.] Marine Biol Lab, Woods Hole, MA 02543 USA.
[Grant, Philip; Pant, Harish C.] NINDS, Lab Neurochem, Bethesda, MD 20892 USA.
[DeGiorgis, Joseph A.] Providence Coll, Dept Biol, Providence, RI 02918 USA.
[Li, Ka Wan] Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Dept Mol & Cellular Neurobiol, NL-1081 HV Amsterdam, Netherlands.
RP Burbach, JPH (reprint author), Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Translat Neurosci, NL-3584 CG Utrecht, Netherlands.
EM j.p.h.burbach@umcutrecht.nl
FU David de Wied Foundation; MBL Fellowship Program; Baxter Postdoctoral
Fellowship Fund; MBL Associates Fund; James A. and Faith Miller Memorial
Fund; H. B. Steinbach Fund; Hersenstichting Nederland; NIGMS [8 P20
GM103430-11]; National Institutes of Health; Intramural Research Program
of the NINDS, National Institutes of Health
FX This research was supported by the David de Wied Foundation, the MBL
Fellowship Program, the Baxter Postdoctoral Fellowship Fund, the MBL
Associates Fund, the James A. and Faith Miller Memorial Fund, the H. B.
Steinbach Fund, the Hersenstichting Nederland (to J.P.H.B.), the
RI-INBRE Grant Award [8 P20 GM103430-11] from the NIGMS, National
Institutes of Health (to J.A.D.), and Intramural Research Program of the
NINDS, National Institutes of Health (to H.C.P.).
NR 52
TC 3
Z9 3
U1 0
U2 6
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 2046-6390
J9 BIOL OPEN
JI Biol. Open
PD JAN 15
PY 2014
VL 3
IS 1
BP 50
EP 58
DI 10.1242/bio.20136890
PG 9
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA AZ2LL
UT WOS:000348065000006
PM 24326188
ER
PT J
AU Mooney, MM
Welch, J
Abrams, JS
AF Mooney, Margaret M.
Welch, Jack
Abrams, Jeffrey S.
TI Clinical trial design and master protocols in NCI clinical treatment
trials.
SO CLINICAL CANCER RESEARCH
LA English
DT Meeting Abstract
CT 3rd AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer
CY JAN 06-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res, IASLC
C1 [Mooney, Margaret M.; Welch, Jack; Abrams, Jeffrey S.] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JAN 15
PY 2014
VL 20
SU 2
MA IA08
DI 10.1158/1078-0432.14AACRIASLC-IA08
PG 1
WC Oncology
SC Oncology
GA CR5LV
UT WOS:000361385000058
ER
PT J
AU Okayama, H
Schetter, AJ
Ishigame, T
Robles, AI
Kohno, T
Yokota, J
Takenoshita, S
Harris, CC
AF Okayama, Hirokazu
Schetter, Aaron J.
Ishigame, Teruhide
Robles, Ana I.
Kohno, Takashi
Yokota, Jun
Takenoshita, Seiichi
Harris, Curtis C.
TI The expression of four genes as a prognostic classifier for stage I lung
adenocarcinoma in 12 independent cohorts.
SO CLINICAL CANCER RESEARCH
LA English
DT Meeting Abstract
CT 3rd AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer
CY JAN 06-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res, IASLC
C1 [Okayama, Hirokazu; Schetter, Aaron J.; Ishigame, Teruhide; Robles, Ana I.; Harris, Curtis C.] NCI, Bethesda, MD 20892 USA.
[Kohno, Takashi] Natl Canc Ctr, Res Inst, Tokyo 104, Japan.
[Yokota, Jun] Inst Predict & Personalized Med Canc, Barcelona, Spain.
[Takenoshita, Seiichi] Fukushima Med Univ, Sch Med, Fukushima, Japan.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JAN 15
PY 2014
VL 20
SU 2
MA B35
DI 10.1158/1078-0432.14AACRIASLC-B35
PG 1
WC Oncology
SC Oncology
GA CR5LV
UT WOS:000361385000053
ER
PT J
AU Robles, AI
Ryan, BM
Aploks, K
Tang, BW
Wakefield, L
Harris, CC
AF Robles, Ana I.
Ryan, Brid M.
Aploks, Krist
Tang, Binwu
Wakefield, Lalage
Harris, Curtis C.
TI A pluripotency reporter defines lung cancer cells with tumor-initiating
properties.
SO CLINICAL CANCER RESEARCH
LA English
DT Meeting Abstract
CT 3rd AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer
CY JAN 06-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res, IASLC
C1 [Robles, Ana I.; Ryan, Brid M.; Aploks, Krist; Tang, Binwu; Wakefield, Lalage; Harris, Curtis C.] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JAN 15
PY 2014
VL 20
SU 2
MA A35
DI 10.1158/1078-0432.14AACRIASLC-A35
PG 1
WC Oncology
SC Oncology
GA CR5LV
UT WOS:000361385000027
ER
PT J
AU Shah, PP
Lockwood, WW
Saurabh, K
Kurlawala, Z
Waigel, S
Zacharias, W
Beverly, LJ
AF Shah, Parag P.
Lockwood, William W.
Saurabh, Kumar
Kurlawala, Zimple
Waigel, Sabine
Zacharias, Wolfgang
Beverly, Levi J.
TI Ubiquilin1 represses migration and epithelial to mesenchymal transition
of human non-small cell lung cancer cells.
SO CLINICAL CANCER RESEARCH
LA English
DT Meeting Abstract
CT 3rd AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer
CY JAN 06-09, 2014
CL San Diego, CA
SP Amer Assoc Canc Res, IASLC
C1 [Shah, Parag P.; Saurabh, Kumar; Kurlawala, Zimple; Waigel, Sabine; Zacharias, Wolfgang; Beverly, Levi J.] Univ Louisville, Louisville, KY 40292 USA.
[Lockwood, William W.] NHGRI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JAN 15
PY 2014
VL 20
SU 2
MA A05
DI 10.1158/1078-0432.14AACRIASLC-A05
PG 1
WC Oncology
SC Oncology
GA CR5LV
UT WOS:000361385000005
ER
PT J
AU Caprioli, D
Sawiak, SJ
Merlo, E
Theobald, DEH
Spoelder, M
Jupp, B
Voon, V
Carpenter, TA
Everitt, BJ
Robbins, TW
Dalley, JW
AF Caprioli, Daniele
Sawiak, Stephen J.
Merlo, Emiliano
Theobald, David E. H.
Spoelder, Marcia
Jupp, Bianca
Voon, Valerie
Carpenter, T. Adrian
Everitt, Barry J.
Robbins, Trevor W.
Dalley, Jeffrey W.
TI Gamma Aminobutyric Acidergic and Neuronal Structural Markers in the
Nucleus Accumbens Core Underlie Trait-like Impulsive Behavior
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Attention-deficit/hyperactivity disorder; GABA; impulsivity; magnetic
resonance imaging; nucleus accumbens; psychostimulants
ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; REACTION-TIME-TASK; DEFICIT
HYPERACTIVITY DISORDER; GLUTAMATE-DECARBOXYLASE GAD65; VOXEL-BASED
MORPHOMETRY; INTER-TEMPORAL CHOICE; PREFRONTAL CORTEX; ANTISENSE
OLIGODEOXYNUCLEOTIDES; RECEPTOR AGONISTS; DELAYED REWARDS
AB Background: Pathological forms of impulsivity are manifest in a number of psychiatric disorders listed in DSM-5, including attention-deficit/hyperactivity disorder and substance use disorder. However, the molecular and cellular substrates of impulsivity are poorly understood. Here, we investigated a specific form of motor impulsivity in rats, namely premature responding, on a five-choice serial reaction time task.
Methods: We used in vivo voxel-based magnetic resonance imaging and ex vivo Western blot analyses to investigate putative structural, neuronal, and glial protein markers in low-impulsive (LI) and high-impulsive rats. We also investigated whether messenger RNA interference targeting glutamate decarboxylase 65/67 (GAD(65/67)) gene expression in the nucleus accumbens core (NAcbC) is sufficient to increase impulsivity in LI rats.
Results: We identified structural and molecular abnormalities in the NAcbC associated with motor impulsivity in rats. We report a reduction in gray matter density in the left NAcbC of high-impulsive rats, with corresponding reductions in this region of glutamate decarboxylase (GAD65/67) and markers of dendritic spines and microtubules. We further demonstrate that the experimental reduction of de novo of GAD65/67 expression bilaterally in the NAcbC is sufficient to increase impulsivity in LI rats.
Conclusions: These results reveal a novel mechanism of impulsivity in rats involving gamma aminobutyric acidergic and structural abnormalities in the NAcbC with potential relevance to the etiology and treatment of attention-deficit/hyperactivity disorder and related disorders.
C1 [Caprioli, Daniele; Sawiak, Stephen J.; Merlo, Emiliano; Theobald, David E. H.; Jupp, Bianca; Voon, Valerie; Carpenter, T. Adrian; Everitt, Barry J.; Robbins, Trevor W.; Dalley, Jeffrey W.] Univ Cambridge, Behav & Clin Neurosci Inst, Cambridge, England.
[Caprioli, Daniele; Sawiak, Stephen J.; Merlo, Emiliano; Theobald, David E. H.; Jupp, Bianca; Voon, Valerie; Carpenter, T. Adrian; Everitt, Barry J.; Robbins, Trevor W.; Dalley, Jeffrey W.] Univ Cambridge, Dept Psychol, Cambridge, England.
[Sawiak, Stephen J.; Carpenter, T. Adrian] Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Wolfson Brain Imaging Ctr, Cambridge CB2 2QQ, England.
[Voon, Valerie; Dalley, Jeffrey W.] Univ Cambridge, Addenbrookes Hosp, Dept Psychiat, Cambridge CB2 2QQ, England.
[Spoelder, Marcia] Univ Utrecht, Dept Anim Sci & Soc, Div Neurobiol Behav, Utrecht, Netherlands.
[Voon, Valerie] Cambridgeshire & Peterborough Natl Hlth Serv Fdn, Cambridge, England.
RP Caprioli, D (reprint author), NIDA, Suite 200,251 Bayview Blvd,Room 08A721, Baltimore, MD 21224 USA.
EM daniele.caprioli@nih.gov
RI Sawiak, Stephen/I-8944-2012;
OI Sawiak, Stephen/0000-0003-4210-9816; Everitt, Barry/0000-0003-4431-6536;
Merlo, Emiliano/0000-0001-9162-6858
FU Medical Research Council
FX This research was supported by an Medical Research Council Grant to JWD,
TWR, BJE, F. I. Aigbirhio, J.- C. Baron, and T. D. Fryer (G0701500); a
Wellcome Trust Programme Grant to TWR, JWD, BJE, A. C. Roberts, and B.
J. Sahakian (089589/Z/09/Z); and by a Core Award from the Medical
Research Council and the Wellcome Trust to the Behavioural and Clinical
Neuroscience Institute (MRC Ref G1000183; WT Ref 093875/Z/10/Z). EM was
supported by a Newton International Fellowship from the Royal Society.
BJ was supported by a Fellowship from the National Health and Medical
Research Council of Australia. VV is a Wellcome Trust Intermediate
Fellow in Clinical Neurosciences.
NR 71
TC 27
Z9 27
U1 0
U2 13
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
EI 1873-2402
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD JAN 15
PY 2014
VL 75
IS 2
BP 115
EP 123
DI 10.1016/j.biopsych.2013.07.013
PG 9
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 269TZ
UT WOS:000328266100006
PM 23973096
ER
PT J
AU Balsam, J
Rasooly, R
Bruck, HA
Rasooly, A
AF Balsam, Joshua
Rasooly, Reuven
Bruck, Hugh Alan
Rasooly, Avraham
TI Thousand-fold fluorescent signal amplification for mHealth diagnostics
SO BIOSENSORS & BIOELECTRONICS
LA English
DT Article
DE Lab-on-a-chip; mHealth; Capillary; Fluorescence; Image stacking; Mobile
phone
ID CELL-PHONE; BIOSENSOR; IMMUNOSENSOR; IMMUNOASSAY; PLATFORM; HEALTH;
SENSOR; POINT
AB The low sensitivity of Mobile Health (mHealth) optical detectors, such as those found on mobile phones, is a limiting factor for many mHealth clinical applications. To improve sensitivity, we have combined two approaches for optical signal amplification: (1) a computational approach based on an image stacking algorithm to decrease the image noise and enhance weak signals, and (2) an optical signal amplifier utilizing a capillary tube array. These approaches were used in a detection system which includes multi-wavelength LEDs capable of exciting many fluorophores in multiple wavelengths, a mobile phone or a webcam as a detector, and capillary tube array configured with 36 capillary tubes for signal enhancement.
The capillary array enables a similar to 100 x increase in signal sensitivity for fluorescein, reducing the limit of detection (LOD) for mobile phones and webcams from 1000 nM to 10 nM. Computational image stacking enables another similar to 10 x increase in signal sensitivity, further reducing the LOD for webcam from 10 nM to 1 nM.
To demonstrate the feasibility of the device for the detection of disease-related biomarkers, adenovirus DNA labeled with SYBR green or fluorescein was analyzed by both our capillary array and a commercial plate reader. The LOD for the capillary array was 5 ug/mL, and that of the plate reader was 1 ug/mL. Similar results were obtained using DNA stained with fluorescein.
The combination of the two signal amplification approaches enables a similar to 1000 x increase in LOD for the webcam platform. This brings it into the range of a conventional plate reader while using a smaller sample volume (10 ul) than the plate reader requires (100 ul). This suggests that such a device could be suitable for biosensing applications where up to 10 fold smaller sample sizes are needed.
The simple optical configuration for mHealth described in this paper employing the combined capillary and image processing signal amplification is capable of measuring weak fluorescent signals without the need of dedicated laboratories. It has the potential to be used to increase sensitivity of other optically based mHealth technologies, and may increase mHealth's clinical utility, especially for telemedicine and for resource-poor settings and global health applications. Published by Elsevier B.V.
C1 [Balsam, Joshua; Rasooly, Avraham] FDA, Div Biol, Off Sci & Engn, Silver Spring, MD 20993 USA.
[Balsam, Joshua; Bruck, Hugh Alan] Univ Maryland, College Pk, MD 20742 USA.
[Rasooly, Reuven] ARS, Western Reg Res Ctr, USDA, Albany, CA 94710 USA.
[Rasooly, Avraham] NCI, Div Canc Biol, Bethesda, MD 20892 USA.
RP Rasooly, A (reprint author), FDA, Div Biol, Off Sci & Engn, Silver Spring, MD 20993 USA.
EM rasoolya@mail.nih.gov
FU FDA's Center for Devices and Radiological Health, Division of Biology;
National Cancer Institute
FX This work was supported by the FDA's Center for Devices and Radiological
Health, Division of Biology and the National Cancer Institute. The views
expressed are those of the authors and do not represent those of the
U.S. Government.
NR 35
TC 9
Z9 9
U1 5
U2 84
PU ELSEVIER ADVANCED TECHNOLOGY
PI OXFORD
PA OXFORD FULFILLMENT CENTRE THE BOULEVARD, LANGFORD LANE, KIDLINGTON,
OXFORD OX5 1GB, OXON, ENGLAND
SN 0956-5663
EI 1873-4235
J9 BIOSENS BIOELECTRON
JI Biosens. Bioelectron.
PD JAN 15
PY 2014
VL 51
BP 1
EP 7
DI 10.1016/j.bios.2013.06.053
PG 7
WC Biophysics; Biotechnology & Applied Microbiology; Chemistry, Analytical;
Electrochemistry; Nanoscience & Nanotechnology
SC Biophysics; Biotechnology & Applied Microbiology; Chemistry;
Electrochemistry; Science & Technology - Other Topics
GA 251CN
UT WOS:000326905500001
PM 23928092
ER
PT J
AU Karami, S
Daugherty, SE
Purdue, MP
AF Karami, Sara
Daugherty, Sarah E.
Purdue, Mark P.
TI Hysterectomy and kidney cancer risk: A meta-analysis
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE hysterectomy; kidney cancer; meta-analysis
ID RENAL-CELL CARCINOMA; REPRODUCTIVE FACTORS; UTERINE PROLAPSE; FAILURE
SECONDARY; PUBLICATION BIAS; OVARIAN-CANCER; UNITED-STATES; DISEASE;
ENDOMETRIOSIS; COHORT
AB Recent cohort findings suggest that women who underwent a hysterectomy have an elevated relative risk of kidney cancer, although evidence from past studies has been inconsistent. We conducted a systematic review and meta-analysis of published cohort and case-control studies to summarize the epidemiologic evidence investigating hysterectomy and kidney cancer. Studies published from 1950 through 2012 were identified through a search of PubMed and of references from relevant publications. Meta-analyses were conducted using random-effects models to estimate summary relative risks (SRRs) and 95% confidence intervals (CIs) for hysterectomy, age at hysterectomy (<45, 45+ years) and time since hysterectomy (<10, 10+ years). The SRR for hysterectomy and kidney cancer for all published studies (seven cohort, six case-control) was 1.29 (95% CI, 1.16-1.43), with no evidence of between-study heterogeneity or publication bias. The summary effect was slightly weaker, although still significant, for cohorts (SRR, 1.26; 95% CI, 1.11-1.42) compared with case-control findings (1.37; 95% CI, 1.09-1.73) and was observed irrespective of age at hysterectomy, time since the procedure and model adjustment for body mass index, smoking status and hypertension. Women undergoing a hysterectomy have an approximate 30% increased relative risk of subsequent kidney cancer. Additional research is needed to elucidate the biological mechanisms underlying this association.
C1 [Karami, Sara; Daugherty, Sarah E.; Purdue, Mark P.] NCI, NIH, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Karami, S (reprint author), NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, 9609 Med Ctr Dr, Rockville, MD 20850 USA.
EM karamis@mail.nih.gov
RI Purdue, Mark/C-9228-2016
OI Purdue, Mark/0000-0003-1177-3108
FU NCI, Division of Cancer Epidemiology and Genetics, National Institutes
of Health
FX Grant sponsor: Intramural Research Program of the NCI, Division of
Cancer Epidemiology and Genetics, National Institutes of Health.
NR 48
TC 2
Z9 2
U1 1
U2 22
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 JAN 15
PY 2014
VL 134
IS 2
BP 405
EP 410
DI 10.1002/ijc.28352
PG 6
WC Oncology
SC Oncology
GA 247VA
UT WOS:000326649300067
PM 23818138
ER
PT J
AU Koshiol, J
Sklavos, M
Wentzensen, N
Kemp, T
Schiffman, M
Dunn, ST
Wang, SS
Walker, JL
Safaeian, M
Zuna, RE
Hildesheim, A
Pfeiffer, RM
Pinto, LA
AF Koshiol, Jill
Sklavos, Martha
Wentzensen, Nicolas
Kemp, Troy
Schiffman, Mark
Dunn, S. Terence
Wang, Sophia S.
Walker, Joan L.
Safaeian, Mahboobeh
Zuna, Rosemary E.
Hildesheim, Allan
Pfeiffer, Ruth M.
Pinto, Ligia A.
TI Evaluation of a multiplex panel of immune-related markers in cervical
secretions: A methodologic study
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE human papillomavirus; immunology; cervical secretions; cervical
intraepithelial neoplasia
ID HUMAN-PAPILLOMAVIRUS INFECTION; EARLY END-POINTS; CERVICOVAGINAL
SECRETIONS; YOUNG-WOMEN; CYTOKINE; SMOKING; INTERLEUKIN-10; NEOPLASIA;
CANCER; TIME
AB Although persistent carcinogenic human papillomavirus (HPV) infection is necessary for cervical carcinogenesis, the cofactors involved in HPV persistence and disease progression are poorly understood. Chronic cervical inflammation may increase risk, but few studies have measured immune markers (cytokines, chemokines and soluble receptors) in cervical secretions. We evaluated the performance of 74 multiplexed, bead-based immune markers in cervical secretions from three groups of women with biopsy evaluation of cervical intraepithelial neoplasia (CIN), (i) 25% detectability and >80% interclass correlation coefficients (ICCs) acceptable for epidemiologic studies. Within-batch coefficients of variation (CVs) of 25% indicated room for assay improvement. Secondarily, we explored associations between marker levels and CIN/HPV status adjusted for matching variables, assay batch, age and number of sexual partners. Sixty-two markers (84%) had >25% detectability and ICCs > 80%. Of those, 53 (85%) had CVs < 25%. Using these preliminary data, we found that HPV positivity was associated with increased eotaxin-1 [odds ratio (OR): 15.63, 95% confidence interval (CI): 1.26-200.00] and G-CSF (OR: 12.99, 95% CI: 1.10-142.86) among CIN-negative women. There was suggestive evidence that higher chemoattractant marker levels were associated with CIN2/3 (e.g., MIP-1delta, OR: 4.48, 95% CI: 0.87-23.04 versus