FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Qin, HY
Cho, M
Haso, W
Zhang, L
Tasian, SK
Oo, HZ
Negri, GL
Lin, YS
Zou, JZ
Mallon, BS
Maude, S
Teachey, DT
Barrett, DM
Orentas, RJ
Daugaard, M
Sorensen, PHB
Grupp, SA
Fry, TJ
AF Qin, Haiying
Cho, Monica
Haso, Waleed
Zhang, Ling
Tasian, Sarah K.
Oo, Htoo Zarni
Negri, Gian Luca
Lin, Yongshun
Zou, Jizhong
Mallon, Barbara S.
Maude, Shannon
Teachey, David T.
Barrett, David M.
Orentas, Rimas J.
Daugaard, Mads
Sorensen, Poul H. B.
Grupp, Stephan A.
Fry, Terry J.
TI Eradication of B-ALL using chimeric antigen receptor-expressing T cells
targeting the TSLPR oncoprotein
SO BLOOD
LA English
DT Article
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; THYMIC STROMAL LYMPHOPOIETIN; MINIMAL
RESIDUAL DISEASE; CHILDRENS ONCOLOGY GROUP; POOR-PROGNOSIS; ADOPTIVE
IMMUNOTHERAPY; IN-VIVO; CRLF2; IKZF1; REARRANGEMENT
AB Adoptive transfer of T cells genetically modified to express chimeric antigen receptors (CARs) targeting the CD19 B cell-associated protein have demonstrated potent activity against relapsed/refractory B-lineage acute lymphoblastic leukemia (B-ALL). Not all patients respond, and CD19-negative relapses have been observed. Overexpression of the thymic stromal lymphopoietin receptor (TSLPR; encoded by CRLF2) occurs in a subset of adults and children with B-ALL and confers a high risk of relapse. Recent data suggest the TSLPR signaling axis is functionally important, suggesting that TSLPR would be an ideal immunotherapeutic target. We constructed short and long CARs targeting TSLPR and tested efficacy against CRLF2-overexpressing B-ALL. Both CARs demonstrated activity in vitro, but only short TSLPRCART cells mediated leukemia regression. In vivo activity of the short CAR was also associated with long-term persistence of CAR-expressing T cells. Short TSLPR CAR treatment of mice engrafted with a TSLPR-expressing ALL cell line induced leukemia cytotoxicity with efficacy comparable with that of CD19 CART cells. Short TSLPR CAR T cells also eradicated leukemia in 4 xenograft models of human CRLF2-over expressing ALL. Finally, TSLPR has limited surface expression on normal tissues. TSLPR-targeted CAR T cells thus represent a potent oncoprotein-targeted immunotherapy for high-risk ALL.
C1 [Qin, Haiying; Cho, Monica; Haso, Waleed; Zhang, Ling; Orentas, Rimas J.; Fry, Terry J.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20816 USA.
[Tasian, Sarah K.; Maude, Shannon; Teachey, David T.; Barrett, David M.; Grupp, Stephan A.] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA.
[Tasian, Sarah K.; Maude, Shannon; Teachey, David T.; Barrett, David M.; Grupp, Stephan A.] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Oo, Htoo Zarni; Daugaard, Mads] Vancouver Prostate Ctr, Vancouver, BC, Canada.
[Oo, Htoo Zarni; Daugaard, Mads] Univ British Columbia, Dept Urol Sci, Vancouver, BC V5Z 1M9, Canada.
[Negri, Gian Luca; Sorensen, Poul H. B.] BC Canc Agcy, Dept Mol Oncol, Vancouver, BC, Canada.
[Lin, Yongshun; Zou, Jizhong] NHLBI, iPSC Core, NIH, Bethesda, MD 20892 USA.
[Mallon, Barbara S.] NINDS, NIH, Stem Cell Unit, Bethesda, MD 20892 USA.
RP Fry, TJ (reprint author), NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20816 USA.
EM fryt@mail.nih.gov
FU Stand Up To Cancer St. Baldrick's Pediatric Dream Team Translational
Research Grant [SU2C-AACR-DT1113]; William Lawrence and Blanche Hughes
Foundation; National Institutes of Health, National Cancer Institute
[UMICA1837390]; Alex's Lemonade Stand Foundation (ALSF); National Center
For Research Resources [UL1RR024134]; National Cancer Institute
[K08CA184418]
FX These studies were supported in part by the Stand Up To Cancer St.
Baldrick's Pediatric Dream Team Translational Research Grant
(SU2C-AACR-DT1113) (S.K.T., M.D., D.M.B., R.J.O., P.H.B.S., S.A.G.,
T.J.F.); a grant from the William Lawrence and Blanche Hughes Foundation
(T.J.F.); National Institutes of Health, National Cancer
Institute-supported CHTN (UMICA1837390); the Alex's Lemonade Stand
Foundation (ALSF), the University of Pennsylvania Institute for
Translational Medicine and Therapeutics (ITMAT)
Trans-disciplinaryProgram in Translational Medicine and Therapeutics
(UL1RR024134 from the National Center For Research Resources), and the
National Cancer Institute (K08CA184418) (S.K.T.).
NR 49
TC 18
Z9 19
U1 2
U2 13
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 JUL 30
PY 2015
VL 126
IS 5
BP 629
EP 639
DI 10.1182/blood-2014-11-612903
PG 11
WC Hematology
SC Hematology
GA CO0VO
UT WOS:000358871900015
PM 26041741
ER
PT J
AU Krivega, I
Byrnes, C
de Vasconcellos, JF
Lee, YT
Kaushal, M
Dean, A
Miller, JL
AF Krivega, Ivan
Byrnes, Colleen
de Vasconcellos, Jaira F.
Lee, Y. Terry
Kaushal, Megha
Dean, Ann
Miller, Jeffery L.
TI Inhibition of G9a methyltransferase stimulates fetal hemoglobin
production by facilitating LCR/gamma-globin looping
SO BLOOD
LA English
DT Article
ID ADULT ERYTHROID-CELLS; GAMMA-GLOBIN; HISTONE MODIFICATIONS; CHEMICAL
PROBE; GENE; METHYLATION; TRANSCRIPTION; H3K9; GLP; EXPRESSION
AB Induction of fetal hemoglobin (HbF) production in adult erythrocytes can reduce the severity of sickle cell disease and beta-thalassemia. Transcription of beta-globin genes is regulated by the distant locus control region (LCR), which is brought into direct gene contact by the LDB1/GATA-1/TAL1/LMO2-containing complex. Inhibition of G9a H3K9 methyltransferase by the chemical compound UNC0638 activates fetal and represses adult b-globin gene expression in adult human hematopoietic precursor cells, but the underlying mechanisms are unclear. Here we studied UNC0638 effects on beta-globin gene expression using ex vivo differentiation of CD34(+) erythroid progenitor cells from peripheral blood of healthy adult donors. UNC0638 inhibition of G9a caused dosed accumulation of HbF up to 30% of total hemoglobin in differentiated cells. Elevation of HbF was associated with significant activation of fetal gamma-globin and repression of adult beta-globin transcription. Changes in gene expression were associated with widespread loss of H3K9me2 in the locus and gain of LDB1 complex occupancy at the gamma-globin promoters as well as de novo formation of LCR/gamma-globin contacts. Our findings demonstrate that G9a establishes epigenetic conditions preventing activation of gamma-globin genes during differentiation of adult erythroid progenitor cells. In this view, manipulation of G9a represents a promising epigenetic approach for treatment of beta-hemoglobinopathies.
C1 [Krivega, Ivan; Dean, Ann] NIDDK, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA.
[Byrnes, Colleen; de Vasconcellos, Jaira F.; Lee, Y. Terry; Kaushal, Megha; Miller, Jeffery L.] NIDDK, Mol Genom & Therapeut Sect, Mol Med Branch, NIH, Bethesda, MD 20892 USA.
RP Miller, JL (reprint author), NIDDK, Mol Med Branch, NIH, 10 Ctr Dr,Bldg 10,Room 9N311, Bethesda, MD 20892 USA.
EM anndean@helix.nih.gov; jm7f@nih.gov
FU Intramural Research Program of National Institute of Diabetes and
Digestive and Kidney Diseases, National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health.
NR 46
TC 11
Z9 11
U1 1
U2 7
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD JUL 30
PY 2015
VL 126
IS 5
BP 665
EP 672
DI 10.1182/blood-2015-02-629972
PG 8
WC Hematology
SC Hematology
GA CO0VO
UT WOS:000358871900019
PM 25979948
ER
PT J
AU Guerrieri, D
van Praag, H
AF Guerrieri, Davide
van Praag, Henriette
TI Exercise-mimetic AICAR transiently benefits brain function
SO ONCOTARGET
LA English
DT Article
DE Gerotarget; running; AMPK; AICAR; hippocampus; muscle
ID ACTIVATED PROTEIN-KINASE; SKELETAL-MUSCLE; NITRIC-OXIDE;
GENE-EXPRESSION; HIPPOCAMPAL NEUROGENESIS; SYNAPTIC PLASTICITY;
GROWTH-FACTOR; DENTATE GYRUS; IN-VIVO; VOLUNTARY EXERCISE
AB Exercise enhances learning and memory in animals and humans. The role of peripheral factors that may trigger the beneficial effects of running on brain function has been sparsely examined. In particular, it is unknown whether AMP-kinase (AMPK) activation in muscle can predict enhancement of brain plasticity. Here we compare the effects of running and administration of AMPK agonist 5-Aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside (AICAR, 500 mg/kg), for 3, 7 or 14 days in one-month-old male C57BL/6J mice, on muscle AMPK signaling. At the time-points where we observed equivalent running- and AICAR-induced muscle pAMPK levels (7 and 14 days), cell proliferation, synaptic plasticity and gene expression, as well as markers of oxidative stress and inflammation in the dentate gyrus (DG) of the hippocampus and lateral entorhinal cortex (LEC) were evaluated. At the 7-day time-point, both regimens increased new DG cell number and brain-derived neurotrophic factor (BDNF) protein levels. Furthermore, microarray analysis of DG and LEC tissue showed a remarkable overlap between running and AICAR in the regulation of neuronal, mitochondrial and metabolism related gene classes. Interestingly, while similar outcomes for both treatments were stable over time in muscle, in the brain an inversion occurred at fourteen days. The compound no longer increased DG cell proliferation or neurotrophin levels, and upregulated expression of apoptotic genes and inflammatory cytokine interleukin-1 beta. Thus, an exercise mimetic that produces changes in muscle consistent with those of exercise does not have the same sustainable positive effects on the brain, indicating that only running consistently benefits brain function.
C1 [Guerrieri, Davide; van Praag, Henriette] NIA, Neuroplast & Behav Unit, Lab Neurosci, Baltimore, MD 21224 USA.
RP van Praag, H (reprint author), NIA, Neuroplast & Behav Unit, Lab Neurosci, Baltimore, MD 21224 USA.
EM vanpraagh@mail.nih.gov
RI van Praag, Henriette/F-3939-2015
OI van Praag, Henriette/0000-0002-5727-434X
FU Intramural Research Program of the NIH; National Institute on Aging
(NIA)
FX This research was supported by the Intramural Research Program of the
NIH, National Institute on Aging (NIA).
NR 105
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Z9 5
U1 1
U2 6
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD JUL 30
PY 2015
VL 6
IS 21
BP 18293
EP 18313
PG 21
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA CO2VW
UT WOS:000359015900011
PM 26286955
ER
PT J
AU Zhong, LP
Zhang, CP
Ren, GX
Guo, W
William, WN
Hong, CS
Sun, J
Zhu, HG
Tu, WY
Li, J
Cai, YL
Yin, QM
Wang, LZ
Wang, ZH
Hu, YJ
Ji, T
Yang, WJ
Ye, WM
Li, J
He, Y
Wang, YA
Xu, LQ
Zhuang, ZP
Lee, JJ
Myers, JN
Zhang, ZY
AF Zhong, Lai-ping
Zhang, Chen-ping
Ren, Guo-xin
Guo, Wei
William, William N., Jr.
Hong, Christopher S.
Sun, Jian
Zhu, Han-guang
Tu, Wen-Yong
Li, Jiang
Cai, Yi-li
Yin, Qiu-ming
Wang, Li-zhen
Wang, Zhong-He
Hu, Yong-Jie
Ji, Tong
Yang, Wen-jun
Ye, Wei-Min
Li, Jun
He, Yue
Wang, Yan-An
Xu, Li-Qun
Zhuang, Zhengping
Lee, J. Jack
Myers, Jeffrey N.
Zhang, Zhi-Yuan
TI Long-term results of a randomized phase III trial of TPF induction
chemotherapy followed by surgery and radiation in locally advanced oral
squamous cell carcinoma
SO ONCOTARGET
LA English
DT Article
DE induction chemotherapy; oral squamous cell carcinoma; cisplatin;
docetaxel; 5-fluorouracil
ID NECK-CANCER; ADVANCED HEAD; FLUOROURACIL; CISPLATIN; DOCETAXEL;
METAANALYSIS
AB Previously, we conducted a randomized phase III trial of TPF (docetaxel, cisplatin, and 5-fluorouracil) induction chemotherapy in surgically managed locally advanced oral squamous cell carcinoma (OSCC) and found no improvement in overall survival. This study reports long-term follow-up results from our initial trial. All patients had clinical stage III or IVA locally advanced OSCC. In the experimental group, patients received two cycles of TPF induction chemotherapy (75mg/m(2) docetaxel d1, 75mg/m(2) cisplatin d1, and 750mg/m(2)/day 5-fluorouracil d1-5) followed by radical surgery and post-operative radiotherapy; in the control group, patients received upfront radical surgery and post-operative radiotherapy. The primary endpoint was overall survival. Among 256 enrolled patients with a median follow-up of 70 months, estimated 5-year overall survival, disease-free survival, locoregional recurrence-free survival, and distant metastasis-free survival rates were 61.1%, 52.7%, 55.2%, and 60.4%, respectively. There were no significant differences in survival rates between experimental and control groups. However, patients with favorable pathologic responses had improved outcomes compared to those with unfavorable pathologic responses and to those in the control group. Although TPF induction chemotherapy did not improve long-term survival compared to surgery upfront in patients with stage III and IVA OSCC, a favorable pathologic response after induction chemotherapy may be used as a major endpoint and prognosticator in future studies. Furthermore, the negative results observed in this trial may be represent type II error from an underpowered study. Future larger scale phase III trials are warranted to investigate whether a significant benefit exists for TPF induction chemotherapy in surgically managed OSCC.
C1 [Zhong, Lai-ping; Zhang, Chen-ping; Ren, Guo-xin; Guo, Wei; Sun, Jian; Zhu, Han-guang; Tu, Wen-Yong; Cai, Yi-li; Yin, Qiu-ming; Wang, Zhong-He; Hu, Yong-Jie; Ji, Tong; Yang, Wen-jun; Ye, Wei-Min; Li, Jun; He, Yue; Wang, Yan-An; Xu, Li-Qun; Zhang, Zhi-Yuan] Shanghai Jiao Tong Univ, Sch Med, Dept Oral & Maxillofacial Head & Neck Oncol, Ninth Peoples Hosp,Coll Stomatol, Shanghai 200030, Peoples R China.
[William, William N., Jr.] Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA.
[Hong, Christopher S.; Zhuang, Zhengping] Natl Inst Hlth, Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA.
[Li, Jiang; Wang, Li-zhen] Shanghai Jiao Tong Univ, Sch Med, Dept Oral Pathol, Ninth Peoples Hosp,Coll Stomatol, Shanghai 200030, Peoples R China.
[Lee, J. Jack] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA.
[Myers, Jeffrey N.] Univ Texas MD Anderson Canc Ctr, Dept Head & Neck Surg, Houston, TX 77030 USA.
RP Zhang, ZY (reprint author), Shanghai Jiao Tong Univ, Sch Med, Dept Oral & Maxillofacial Head & Neck Oncol, Ninth Peoples Hosp,Coll Stomatol, Shanghai 200030, Peoples R China.
EM zhang.z.y@hotmail.com
FU National Key Technology R&D Program of China [2007BAI18B03]; National
Natural Science Foundation of China [81272979, 81472519]; Science and
Technology Commission of Shanghai Municipality [13QH1401700]; Shanghai
Municipal Human Resources and Social Security Bureau [201447];
Intramural Research Program of the National Institute of Neuroogical
Disorders and Stroke at the National Institutes of Health
FX This study was supported by research grant 2007BAI18B03 from National
Key Technology R&D Program of China; by research grants 81272979 and
81472519 from National Natural Science Foundation of China; by research
grant 13QH1401700 from Science and Technology Commission of Shanghai
Municipality; by research grant 201447 from Shanghai Municipal Human
Resources and Social Security Bureau. Additional support was provided by
the Intramural Research Program of the National Institute of Neuroogical
Disorders and Stroke at the National Institutes of Health (Bethesda, MD,
USA).
NR 19
TC 5
Z9 5
U1 1
U2 2
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD JUL 30
PY 2015
VL 6
IS 21
BP 18707
EP 18714
PG 8
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA CO2VW
UT WOS:000359015900041
PM 26124084
ER
PT J
AU Brown, RJ
Meehan, CA
Gorden, P
AF Brown, Rebecca J.
Meehan, Cristina Adelia
Gorden, Phillip
TI Leptin Does Not Mediate Hypertension Associated With Human Obesity
SO CELL
LA English
DT Editorial Material
AB Hypertension and obesity are known to be linked, with recent studies in mice proposing that leptin may be mediating this effect. This regulation, however, may not extend to humans, where a yet-to-be-identified factor is likely the underlying cause of hypertension.
C1 [Brown, Rebecca J.; Meehan, Cristina Adelia; Gorden, Phillip] NIDDK, Diabetes Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA.
RP Gorden, P (reprint author), NIDDK, Diabetes Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA.
EM phillipg@intra.niddk.nih.gov
NR 4
TC 9
Z9 9
U1 1
U2 15
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 JUL 30
PY 2015
VL 162
IS 3
BP 465
EP 466
DI 10.1016/j.cell.2015.07.007
PG 2
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CN9WS
UT WOS:000358801800002
PM 26232214
ER
PT J
AU Diamond, MS
Pierson, TC
AF Diamond, Michael S.
Pierson, Theodore C.
TI Molecular Insight into Dengue Virus Pathogenesis and Its Implications
for Disease Control
SO CELL
LA English
DT Review
ID IN-VITRO; INFECTION; FLAVIVIRUSES; ENHANCEMENT; STABILITY; DYNAMICS;
BIOLOGY; PROTEIN; BURDEN; IMPACT
AB Dengue virus (DENV) is a mosquito-transmitted RNA virus that infects an estimated 390 million humans each year. Here, we review recent advances in our understanding of the biology of DENV and describe knowledge gaps that have impacted the development of effective vaccines and therapeutics.
C1 [Diamond, Michael S.] Washington Univ, Sch Med, Ctr Human Immunol & Immunotherapy Programs, Dept Med, St Louis, MO 63110 USA.
[Diamond, Michael S.] Washington Univ, Sch Med, Ctr Human Immunol & Immunotherapy Programs, Dept Mol Microbiol, St Louis, MO 63110 USA.
[Diamond, Michael S.] Washington Univ, Sch Med, Ctr Human Immunol & Immunotherapy Programs, Dept Pathol & Immunol, St Louis, MO 63110 USA.
[Pierson, Theodore C.] NIAID, Viral Pathogenesis Sect, NIH, Bethesda, MD 20892 USA.
RP Diamond, MS (reprint author), Washington Univ, Sch Med, Ctr Human Immunol & Immunotherapy Programs, Dept Med, St Louis, MO 63110 USA.
EM diamond@wusm.wustl.edu; piersontc@mail.nih.gov
FU National Institute of Allergy and Infectious Diseases; Burroughs
Wellcome Fund; NIH [R01 AI073755, R01 AI098723]
FX This work was supported by the intramural program of the National
Institute of Allergy and Infectious Diseases, the Burroughs Wellcome
Fund, and NIH grants R01 AI073755 and R01 AI098723. We sincerely
apologize to our colleagues whose primary studies we were unable to cite
due to the limited scope and citation restrictions of this Review.
M.S.D. has served as an ad hoc member of the external Scientific
Advisory Board of Sanofi-Pasteur.
NR 31
TC 22
Z9 23
U1 3
U2 24
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 JUL 30
PY 2015
VL 162
IS 3
BP 488
EP 492
DI 10.1016/j.cell.2015.07.005
PG 5
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CN9WS
UT WOS:000358801800009
PM 26232221
ER
PT J
AU Di Narzo, AF
Kozlenkov, A
Ge, YC
Zhang, B
Sanelli, L
May, Z
Li, YQ
Fouad, K
Cardozo, C
Koonin, EV
Bennett, DJ
Dracheva, S
AF Di Narzo, Antonio Fabio
Kozlenkov, Alexey
Ge, Yongchao
Zhang, Bin
Sanelli, Leo
May, Zacnicte
Li, Yanqing
Fouad, Karim
Cardozo, Christopher
Koonin, Eugene V.
Bennett, David J.
Dracheva, Stella
TI Decrease of mRNA Editing after Spinal Cord Injury is Caused by
Down-regulation of ADAR2 that is Triggered by Inflammatory Response
SO SCIENTIFIC REPORTS
LA English
DT Article
ID AMYOTROPHIC-LATERAL-SCLEROSIS; SEROTONIN 2C; CONSTITUTIVE ACTIVITY;
PREFRONTAL CORTEX; PERSISTENT SODIUM; EXPRESSION DATA; 2A RECEPTORS;
HUMAN BRAIN; MOTONEURONS; RATS
AB We recently showed that spinal cord injury (SCI) leads to a decrease in mRNA editing of serotonin receptor 2C (5-HT2CR) contributing to post-SCI spasticity. Here we study post-SCI mRNA editing and global gene expression using massively parallel sequencing. Evidence is presented that the decrease in 5-HT2CR editing is caused by down-regulation of adenosine deaminase ADAR2 and that editing of at least one other ADAR2 target, potassium channel Kv1.1, is decreased after SCI. Bayesian network analysis of genome-wide transcriptome data indicates that down-regulation of ADAR2 (1) is triggered by persistent inflammatory response to SCI that is associated with activation of microglia and (2) results in changes in neuronal gene expression that are likely to contribute both to post-SCI restoration of neuronal excitability and muscle spasms. These findings have broad implications for other diseases of the Central Nervous System and could open new avenues for developing efficacious antispastic treatments.
C1 [Di Narzo, Antonio Fabio; Zhang, Bin] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA.
[Kozlenkov, Alexey; Dracheva, Stella] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA.
[Kozlenkov, Alexey; Dracheva, Stella] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA.
[Kozlenkov, Alexey; Cardozo, Christopher; Dracheva, Stella] James J Peters VA Med Ctr, Bronx, NY USA.
[Ge, Yongchao] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA.
[Sanelli, Leo; May, Zacnicte; Li, Yanqing; Fouad, Karim; Bennett, David J.] Univ Alberta, Fac Rehabil Med, Ctr Neurosci, Edmonton, AB, Canada.
[Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
RP Dracheva, S (reprint author), Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA.
EM Stella.Dracheva@mssm.edu
FU VISN3 Mental Illness Research and Education Clinical Center (MIRECC); VA
Merit Review Award [BX002343]; intramural funds of the US Department of
Health and Human Services
FX The work was supported with resources and the use of facilities at the
James J Peters VA Medical Center, Bronx, New York and funded by: VISN3
Mental Illness Research and Education Clinical Center (MIRECC) and VA
Merit Review Award (BX002343 to S.D.). E.V.K. is supported by intramural
funds of the US Department of Health and Human Services to National
Library of Medicine.
NR 57
TC 4
Z9 4
U1 1
U2 5
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 JUL 30
PY 2015
VL 5
AR 12615
DI 10.1038/srep12615
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CO0UY
UT WOS:000358870200001
PM 26223940
ER
PT J
AU Fan, JB
Arimoto, KI
Motamedchaboki, K
Yan, M
Wolf, DA
Zhang, DE
AF Fan, Jun-Bao
Arimoto, Kei-Ichiro
Motamedchaboki, Khatereh
Yan, Ming
Wolf, Dieter A.
Zhang, Dong-Er
TI Identification and characterization of a novel ISG15-ubiquitin mixed
chain and its role in regulating protein homeostasis
SO SCIENTIFIC REPORTS
LA English
DT Article
ID UBIQUITIN-LIKE PROTEIN; PROTEASOMAL DEGRADATION; ISG15 MODIFICATION;
POLYUBIQUITIN CHAINS; CONJUGATING ENZYME; TUMOR-CELLS; ACTIVATION;
LIGASE; PATHWAY; ISGYLATION
AB As a ubiquitin-like modifier, ISG25 is conjugated to many cellular proteins in a process termed protein ISGylation. However, the crosstalk between protein ISGylation and the ubiquitin proteasome system is not fully understood. Here, we report that cellular ubiquitin is a substrate of ISG25 and Lys 29 on ubiquitin is the major ISG25 acceptor site. Using a model substrate, we demonstrate that ISG25 can modify ubiquitin, which is immobilized on its substrate, to form ISG25-ubiquitin mixed chains. Furthermore, our results indicate that ISG25-ubiquitin mixed chains do not serve as degradation signals for a ubiquitin fusion degradation substrate. Accordingly, an ISG25-ubiquitin fusion protein, which mimics an ISG25-ubiquitin mixed chain, negatively regulates cellular turnover of ubiquitylated proteins. In addition, ISG25-ubiquitin mixed chains, which are detectable on endogenously ubiquitylated proteins, dampen cellular turnover of these proteins. Thus, our studies unveil an unanticipated interplay between two protein modification systems and highlight its role in coordinating protein homeostasis.
C1 [Fan, Jun-Bao; Arimoto, Kei-Ichiro; Yan, Ming; Zhang, Dong-Er] Univ Calif San Diego, Moores UCSD Canc Ctr, La Jolla, CA 92093 USA.
[Motamedchaboki, Khatereh; Wolf, Dieter A.] NCI, Canc Ctr Prote Facil, Sanford Burnham Prebys Med Discovery Inst, La Jolla, CA 92037 USA.
[Wolf, Dieter A.] Sanford Burnham Prebys Med Discovery Inst, Tumor Initiat & Maintenance Program, La Jolla, CA 92037 USA.
[Wolf, Dieter A.] San Diego Ctr Syst Biol, La Jolla, CA 92093 USA.
[Zhang, Dong-Er] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA.
[Zhang, Dong-Er] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA.
RP Zhang, DE (reprint author), Univ Calif San Diego, Moores UCSD Canc Ctr, La Jolla, CA 92093 USA.
EM d7zhang@ucsd.edu
RI Fan, Jun-bao/E-7155-2012
FU National Institutes of Health [RO1CA177305, RO1GM105802]; Sanford
Burnham Prebys Medical Discovery Institute NCI Cancer Center Support
Grant [P3OCA030199]; NIGMS San Diego Center for Systems Biology [P50
GM085764]
FX We thank Samuel Stoner for critical editing of this manuscript and all
the Zhang lab members for discussion and help. We gratefully acknowledge
Dr. Debra Lenschow (Washington University School of Medicine, USA) for
providing antibodies to ISG15, Dr. R. Baker (Australian National
University, Canberra, Australia) for UBP41 cDNA and Dr. Michele Pagano
(New York University School of Medicine, USA) for the lysine deficient
Ubiquitin construct. This work was supported by funding from National
Institutes of Health to DEZ (RO1CA177305) and DAW (RO1GM105802), Sanford
Burnham Prebys Medical Discovery Institute NCI Cancer Center Support
Grant to DAW (P3OCA030199) and NIGMS San Diego Center for Systems
Biology grant to DAW (P50 GM085764).
NR 62
TC 1
Z9 1
U1 0
U2 2
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 JUL 30
PY 2015
VL 5
DI 10.1038/srep12704
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CO0TX
UT WOS:000358867300001
PM 26226047
ER
PT J
AU Hejtmancik, JF
AF Hejtmancik, J. Fielding
TI OPHTHALMOLOGY Cataracts dissolved
SO NATURE
LA English
DT Editorial Material
ID CONGENITAL CATARACT; LENS; TRANSPARENCY; AGGREGATION; EYE
AB Mutations underlying hereditary cataracts in two families impair the function of an enzyme that synthesizes the lens molecule lanosterol. The finding may lead to non-surgical prevention and treatment of cataracts. See Letter p.607
C1 NEI, Ophthalm Mol Genet Sect, Ophthalm Genet & Visual Funct Branch, Rockville, MD 20892 USA.
RP Hejtmancik, JF (reprint author), NEI, Ophthalm Mol Genet Sect, Ophthalm Genet & Visual Funct Branch, Rockville, MD 20892 USA.
EM hejtmancikj@nei.nih.gov
NR 16
TC 1
Z9 1
U1 5
U2 21
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 JUL 30
PY 2015
VL 523
IS 7562
BP 540
EP 541
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN7ZL
UT WOS:000358655200032
PM 26200338
ER
PT J
AU Glancy, B
Hartnell, LM
Malide, D
Yu, ZX
Combs, CA
Connelly, PS
Subramaniam, S
Balaban, RS
AF Glancy, Brian
Hartnell, Lisa M.
Malide, Daniela
Yu, Zu-Xi
Combs, Christian A.
Connelly, Patricia S.
Subramaniam, Sriram
Balaban, Robert S.
TI Mitochondrial reticulum for cellular energy distribution in muscle
SO NATURE
LA English
DT Article
ID LIMB SKELETAL-MUSCLE; RAT DIAPHRAGM MUSCLE; IN-VIVO; 3-DIMENSIONAL
RECONSTRUCTION; ELECTRON-MICROSCOPY; CREATINE-KINASE; DEFICIENT;
MYOGLOBIN; MICE; FLUORESCENCE
AB Intracellular energy distribution has attracted much interest and has been proposed to occur in skeletal muscle via metabolite-facilitated diffusion(1,2;) however, genetic evidence suggests that facilitated diffusion is not critical for normal function(3-7). We hypothesized that mitochondrial structure minimizes metabolite diffusion distances in skeletal muscle. Here we demonstrate a mitochondrial reticulum providing a conductive pathway for energy distribution, in the form of the proton-motive force, throughout the mouse skeletal muscle cell. Within this reticulum, we find proteins associated with mitochondrial proton-motive force production preferentially in the cell periphery and proteins that use the proton-motive force for ATP production in the cell interior near contractile and transport ATPases. Furthermore, we show a rapid, coordinated depolarization of the membrane potential component of the proton-motive force throughout the cell in response to spatially controlled uncoupling of the cell interior. We propose that membrane potential conduction via the mitochondrial reticulum is the dominant pathway for skeletal muscle energy distribution.
C1 [Glancy, Brian; Malide, Daniela; Yu, Zu-Xi; Combs, Christian A.; Connelly, Patricia S.; Balaban, Robert S.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Hartnell, Lisa M.; Subramaniam, Sriram] NCI, NIH, Bethesda, MD 20892 USA.
RP Balaban, RS (reprint author), NHLBI, NIH, Bethesda, MD 20892 USA.
EM Robert.Balaban@nih.gov
RI Glancy, Brian/P-3163-2016
OI Glancy, Brian/0000-0002-8571-244X
FU Division of Intramural Research, National Heart, Lung, and Blood
Institute; Center for Cancer Research, National Cancer Institute
FX We would like to thank E. Tyler for his assistance with image rendering,
J. Taraska for providing experimental advice, T. Karpova and the NCI
Core Fluorescence Imaging Facility for access to a microscope with a
355-nm laser, and P. Kellman for assistance with image analysis. We
would also like to thank S. Caldwell and R. Hartley for providing us
with MitoPhotoDNP. This study was supported by intramural funding of the
Division of Intramural Research, National Heart, Lung, and Blood
Institute and the Center for Cancer Research, National Cancer Institute.
NR 33
TC 32
Z9 32
U1 7
U2 26
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 JUL 30
PY 2015
VL 523
IS 7562
BP 617
EP +
DI 10.1038/nature14614
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN7ZL
UT WOS:000358655200050
PM 26223627
ER
PT J
AU Gara, SK
Jia, L
Merino, MJ
Agarwal, SK
Zhang, LS
Cam, M
Patel, D
Kebebew, E
AF Gara, Sudheer Kumar
Jia, Li
Merino, Maria J.
Agarwal, Sunita K.
Zhang, Lisa
Cam, Maggie
Patel, Dhaval
Kebebew, Electron
TI Germline HABP2 Mutation Causing Familial Nonmedullary Thyroid Cancer
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID VII-ACTIVATING PROTEASE; MARBURG-I POLYMORPHISM; HYALURONAN-BINDING
PROTEIN; WILD-TYPE P53; VENOUS THROMBOEMBOLISM; BREAST-CANCER;
CARCINOMA; THROMBOSIS; RISK; IDENTIFICATION
AB Familial nonmedullary thyroid cancer accounts for 3 to 9% of all cases of thyroid cancer, but the susceptibility genes are not known. Here, we report a germline variant of HABP2 in seven affected members of a kindred with familial nonmedullary thyroid cancer and in 4.7% of 423 patients with thyroid cancer. This variant was associated with increased HABP2 protein expression in tumor samples from affected family members, as compared with normal adjacent thyroid tissue and samples from sporadic cancers. Functional studies showed that HABP2 has a tumor-suppressive effect, whereas the G534E variant results in loss of function.
C1 [Gara, Sudheer Kumar; Jia, Li; Patel, Dhaval; Kebebew, Electron] NCI, Endocrine Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Jia, Li] NCI, Bioinformat Core, Ctr Canc Res, Bethesda, MD 20892 USA.
[Merino, Maria J.] NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Cam, Maggie] NCI, Off Sci & Technol Resources, Bethesda, MD 20892 USA.
[Agarwal, Sunita K.] NIDDK, Metab Dis Branch, Bethesda, MD USA.
RP Kebebew, E (reprint author), NCI, Endocrine Oncol Branch, NIH, CRC, Bldg 10,Rm 4W-5952,10 Ctr Dr,MSC 1201, Bethesda, MD 20892 USA.
EM kebebewe@mail.nih.gov
RI Agarwal, Sunita/D-1428-2016; Gara, Sudheer Kumar/E-8084-2016;
OI Agarwal, Sunita/0000-0002-7557-3191; Patel, Dhaval/0000-0002-5744-568X
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health
FX Supported by the Intramural Research Program of the Center for Cancer
Research, National Cancer Institute, National Institutes of Health.
NR 25
TC 30
Z9 30
U1 0
U2 7
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUL 30
PY 2015
VL 373
IS 5
BP 448
EP 455
DI 10.1056/NEJMoa1502449
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA CN8BO
UT WOS:000358662200008
PM 26222560
ER
PT J
AU Mitchell, EM
Lyles, RH
Schisterman, EF
AF Mitchell, Emily M.
Lyles, Robert H.
Schisterman, Enrique F.
TI Positing, fitting, and selecting regression models for pooled biomarker
data
SO STATISTICS IN MEDICINE
LA English
DT Article
DE AIC; biomarkers; gamma; MCEM; pooled specimens; skewness
ID GENERALIZED LINEAR-MODELS; ROC CURVE ANALYSIS; EM ALGORITHM; DISEASE
PREVALENCE; EFFICIENT DESIGN; SAMPLES; SUBJECT; BIOSPECIMENS;
POPULATIONS; LIKELIHOOD
AB Pooling biospecimens prior to performing lab assays can help reduce lab costs, preserve specimens, and reduce information loss when subject to a limit of detection. Because many biomarkers measured in epidemiological studies are positive and right-skewed, proper analysis of pooled specimens requires special methods. In this paper, we develop and compare parametric regression models for skewed outcome data subject to pooling, including a novel parameterization of the gamma distribution that takes full advantage of the gamma summation property. We also develop a Monte Carlo approximation of Akaike's Information Criterion applied to pooled data in order to guide model selection. Simulation studies and analysis of motivating data from the Collaborative Perinatal Project suggest that using Akaike's Information Criterion to select the best parametric model can help ensure valid inference and promote estimate precision. Copyright (C) 2015 John Wiley & Sons, Ltd.
C1 [Mitchell, Emily M.; Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Bethesda, MD 20892 USA.
[Lyles, Robert H.] Emory Univ, Rollins Sch Publ Hlth, Dept Biostat & Bioinformat, Atlanta, GA 30322 USA.
RP Mitchell, EM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Bethesda, MD 20892 USA.
EM emily.mitchell@nih.gov
OI Schisterman, Enrique/0000-0003-3757-641X
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health; Long-Range Research Initiative of the American Chemistry
Council; National Institute of Nursing Research, the National Institute
of Environmental Health Sciences [5R01ES012458-07]; National Center for
Advancing Translational Sciences of the National Institutes of Health
[UL1TR000454]
FX Special thanks to Neil Perkins, Amita Manatunga, Qi Long, Michelle
Danaher, and Brian Whitcomb for their insightful advice. This work was
supported by the Intramural Research Program of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development,
National Institutes of Health; and by the Long-Range Research Initiative
of the American Chemistry Council. Additional support from the National
Institute of Nursing Research, the National Institute of Environmental
Health Sciences [5R01ES012458-07], and the National Center for Advancing
Translational Sciences of the National Institutes of Health [Award
Number UL1TR000454] is also acknowledged. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Institutes of Health.
NR 37
TC 3
Z9 3
U1 1
U2 4
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 JUL 30
PY 2015
VL 34
IS 17
BP 2544
EP 2558
DI 10.1002/sim.6496
PG 15
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 CM1GQ
UT WOS:000357429700005
PM 25846980
ER
PT J
AU Yamazaki, K
Eng, C
Kuznetsov, SA
Reinisch, J
Yamashita, DD
Walker, J
Cheung, C
Robey, PG
Yen, SLK
AF Yamazaki, Kiyomi
Eng, Charis
Kuznetsov, Sergei A.
Reinisch, John
Yamashita, Dennis-Duke
Walker, John
Cheung, Craig
Robey, Pamela G.
Yen, Stephen L-K
TI Missense mutation in the PTEN promoter of a patient with hemifacial
hyperplasia
SO BONEKEY REPORTS
LA English
DT Article
ID MAMMALIAN-CELL SIZE; SYNDROME PLEASE STAND; PROTEUS SYNDROME;
DIAGNOSTIC-CRITERIA; CYCLE PROGRESSION; IN-VIVO; MTOR; SURVIVAL;
PATHWAY; DYSREGULATION
AB The cellular mechanisms involved in the asymmetric facial overgrowth syndrome, hemifacial hyperplasia (HFH), are not well understood. This study was conducted to compare primary cell cultures from hyperplastic and normal HFH bone for cellular and molecular differences. Primary cultures developed from biopsies of a patient with isolated HFH showed a twofold difference in cell size and cell number between hyperplastic and normal bone. Microarray data suggested a 40% suppression of PTEN (phosphatase-tensin homolog) transcripts. Sequencing of the PTEN gene and promoter identified novel C/G missense mutation (position -1053) in the regulatory region of the PTEN promoter. Western blots of downstream pathway components showed an increase in PKBa/Akt1 phosphorylation and TOR (target of rapamcyin) signal. Sirolimus, an inhibitor of TOR, when added to overgrowth cells reversed the cell size, cell number and total protein differences between hyperplastic and normal cells. In cases of facial overgrowth, which involve PTEN/Akt/TOR dysregulation, sirolimus could be used for limiting cell overgrowth.
C1 [Yamazaki, Kiyomi; Reinisch, John; Yamashita, Dennis-Duke; Walker, John; Yen, Stephen L-K] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA.
[Yamazaki, Kiyomi; Cheung, Craig; Yen, Stephen L-K] Univ So Calif, Ctr Craniofacial Mol Biol, CSA 103,2250 Alcazar St, Los Angeles, CA 90033 USA.
[Eng, Charis] Ohio State Univ, Dept Internal Med, Ctr Comprehens Canc, Clin Canc Genet Program,Human Canc Genet Program, Columbus, OH 43210 USA.
[Kuznetsov, Sergei A.; Robey, Pamela G.; Yen, Stephen L-K] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA.
RP Yen, SLK (reprint author), Univ So Calif, Ctr Craniofacial Mol Biol, CSA 103,2250 Alcazar St, Los Angeles, CA 90033 USA.
EM syen@usc.edu
OI Eng, Charis/0000-0002-3693-5145
NR 36
TC 1
Z9 1
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2047-6396
J9 BONEKEY REP
JI BoneKEy Rep.
PD JUL 29
PY 2015
VL 4
AR 654
DI 10.1038/bonekey.2015.21
PG 7
WC Orthopedics
SC Orthopedics
GA DL5QV
UT WOS:000375692800001
PM 26229595
ER
PT J
AU Tilak, G
Prasad, V
Jena, AB
AF Tilak, Gaurie
Prasad, Vinay
Jena, Anupam B.
TI Authorship Inflation in Medical Publications
SO INQUIRY-THE JOURNAL OF HEALTH CARE ORGANIZATION PROVISION AND FINANCING
LA English
DT Article
DE authorship criteria
ID JOURNALS; CREEP
AB The number of authors per manuscript in peer-reviewed medical journals has increased substantially in the last several decades. Several reasons have been offered to explain this authorship growth, including increased researcher collaboration, honorary authorship driven by increased pressures for funding and promotion, the belief that including senior authors will facilitate publication, and the growing complexity of medical research. It is unknown, however, whether authorship has grown over time due to growing complexity of published academic articles, in which case growth could be warranted, or whether it has grown due to pressures of funding and academic promotion, which have created "authorship inflation." To answer this question, we analyzed data on authorship count, study type, and size of study population for the first 50 original articles published in each decade during 1960-2010 in 3 major medical journals. Within each type of study we considered (eg, randomized trials, observational studies, etc), average authorship rose more than 3-fold during this period. Similar growth persisted after adjustment for changes in study population sizes over time. Our findings suggest that increasing research complexity is an inadequate explanation for authorship growth. Instead, growth in authorship appears inflationary.
C1 [Tilak, Gaurie; Jena, Anupam B.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Prasad, Vinay] NIH, Bethesda, MD 20892 USA.
RP Jena, AB (reprint author), Harvard Univ, Sch Med, 180 Longwood Ave, Boston, MA 02115 USA.
EM jena@hcp.med.harvard.edu
OI Prasad, Vinay/0000-0002-6110-8221
FU Office of the Director, National Institutes of Health (NIH Early
Independence Award) [1DP5OD017897-01]
FX The author(s) disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article: Funding
was provided by the Office of the Director, National Institutes of
Health (NIH Early Independence Award, grant 1DP5OD017897-01).
NR 12
TC 2
Z9 2
U1 1
U2 4
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0046-9580
EI 1945-7243
J9 INQUIRY-J HEALTH CAR
JI Inquiry-J. Health Care Organ. Provis. Financ.
PD JUL 29
PY 2015
VL 52
AR 0046958015598311
DI 10.1177/0046958015598311
PG 4
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA CX9BI
UT WOS:000365999300001
ER
PT J
AU Arizpe, JM
Walsh, V
Baker, CI
AF Arizpe, Joseph M.
Walsh, Vincent
Baker, Chris I.
TI Characteristic visuomotor influences on eye-movement patterns to faces
and other high level stimuli
SO FRONTIERS IN PSYCHOLOGY
LA English
DT Article
DE eye movements; distance effect; face recognition; object recognition;
visual perception; visual fields; gaze control; visuomotor control
ID VISUAL-FIELD SUPERIORITY; PERCEPTUAL ASYMMETRIES; RIGHT-HEMISPHERE;
FUNCTIONAL NEUROANATOMY; CHIMERIC STIMULI; TEMPORAL CORTEX; RECOGNITION;
TASK; REPRESENTATIONS; FIXATIONS
AB Eye-movement patterns are often utilized in studies of visual perception as indices of the specific information extracted to efficiently process a given stimulus during a given task. Our prior work, however, revealed that not only the stimulus and task influence eye-movements, but that visuomotor (start position) factors also robustly and characteristically influence eye-movement patterns to faces (Arizpe et al., 2012). Here we manipulated lateral starting side and distance from the midline of face and line-symmetrical control (butterfly) stimuli in order to further investigate the nature and generality of such visuomotor influences. First we found that increasing starting distance from midline (4, 8, 12, and 16 visual angle) strongly and proportionately increased the distance of the first ordinal fixation from midline. We did not find influences of starting distance on subsequent fixations, however, suggesting that eye-movement plans are not strongly affected by starting distance following an initial orienting fixation. Further, we replicated our prior effect of starting side (left, right) to induce a spatially contralateral tendency of fixations after the first ordinal fixation. However, we also established that these visuomotor influences did not depend upon the predictability of the location of the upcoming stimulus, and were present not only for face stimuli but also for our control stimulus category (butterflies). We found a correspondence in overall left-lateralized fixation tendency between faces and butterflies. Finally, for faces, we found a relationship between left starting side (right sided fixation pattern tendency) and increased recognition performance, which likely reflects a cortical right hemisphere (left visual hemifield) advantage for face perception. These results further indicate the importance of considering and controlling for visuomotor influences in the design, analysis, and interpretation of eye-movement studies.
C1 [Arizpe, Joseph M.; Walsh, Vincent] UCL, Inst Cognit Neurosci, Appl Cognit Neurosci, London WC1N 3AR, England.
[Arizpe, Joseph M.; Baker, Chris I.] NIMH, Sect Learning & Plast, NIH, Bethesda, MD 20892 USA.
[Arizpe, Joseph M.] Univ Tennessee, Ctr Hlth Sci, Dept Neurol, Memphis, TN 38163 USA.
[Arizpe, Joseph M.] Le Bonheur Childrens Hosp, Dept Pediat, Memphis, TN USA.
RP Arizpe, JM (reprint author), UCL, Inst Cognit Neurosci, Appl Cognit Neurosci, 17 Queen Sq, London WC1N 3AR, England.
EM joseph.arizpe.10@ucl.ac.uk
RI Arizpe, Joseph/N-1399-2014
OI Arizpe, Joseph/0000-0001-8958-7757
NR 63
TC 3
Z9 3
U1 4
U2 12
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1664-1078
J9 FRONT PSYCHOL
JI Front. Psychol.
PD JUL 29
PY 2015
VL 6
AR 1027
DI 10.3389/fpsyg.2015.01027
PG 14
WC Psychology, Multidisciplinary
SC Psychology
GA CP3IR
UT WOS:000359772900001
PM 26283982
ER
PT J
AU Dickert, NW
Miller, FG
AF Dickert, Neal W.
Miller, Franklin G.
TI Involving patients in enrolment decisions for acute myocardial
infarction trials
SO BMJ-BRITISH MEDICAL JOURNAL
LA English
DT Editorial Material
ID INFORMED-CONSENT; PATIENTS PERCEPTIONS; PRAGMATIC TRIALS
C1 [Dickert, Neal W.] Emory Univ, Sch Med, Dept Med, Atlanta, GA 30322 USA.
[Dickert, Neal W.] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA.
[Miller, Franklin G.] NIH, Dept Bioeth, Bethesda, MD 20892 USA.
RP Dickert, NW (reprint author), Emory Univ, Sch Med, Dept Med, Atlanta, GA 30322 USA.
EM njr@emory.edu
NR 23
TC 5
Z9 5
U1 0
U2 0
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1756-1833
J9 BMJ-BRIT MED J
JI BMJ-British Medical Journal
PD JUL 29
PY 2015
VL 351
AR h3791
DI 10.1136/bmj.h3791
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA CO2UA
UT WOS:000359010900004
PM 26223782
ER
PT J
AU Kim, J
Tanner, K
AF Kim, Jiyun
Tanner, Kandice
TI Recapitulating the tumor ecosystem along the metastatic cascade using 3D
culture models
SO FRONTIERS IN ONCOLOGY
LA English
DT Review
DE tumor microenvironment; 3D culture models; ecology; biomaterials and
nanotechnology; hydrogels
ID CANCER STEM-CELLS; 3-DIMENSIONAL EXTRACELLULAR-MATRIX;
EPITHELIAL-MESENCHYMAL TRANSITION; TISSUE-BASED BIOASSAYS;
ORGANS-ON-CHIPS; BREAST-CANCER; IN-VITRO; INTRATUMOR HETEROGENEITY;
MICROFLUIDIC PLATFORM; MYELOID-LEUKEMIA
AB Advances in cancer research have shown that a tumor can be likened to a foreign species that disrupts delicately balanced ecological interactions, compromising the survival of normal tissue ecosystems. In efforts to mitigate tumor expansion and metastasis, experimental approaches from ecology are becoming more frequently and successfully applied by researchers from diverse disciplines to reverse engineer and re engineer biological systems in order to normalize the tumor ecosystem. We present a review on the use of 3D biomimetic platforms to recapitulate biotic and abiotic components of the tumor ecosystem, in efforts to delineate the underlying mechanisms that drive evolution of tumor heterogeneity, tumor dissemination, and acquisition of drug resistance.
C1 [Kim, Jiyun; Tanner, Kandice] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Kim, Jiyun] Seoul Natl Univ, Nano Syst Inst, Seoul, South Korea.
RP Tanner, K (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr, Bethesda, MD 20892 USA.
EM kandice.tanner@nih.gov
NR 266
TC 4
Z9 4
U1 4
U2 26
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 2234-943X
J9 FRONT ONCOL
JI Front. Oncol.
PD JUL 29
PY 2015
VL 5
AR 170
DI 10.3389/fonc.2015.00170
PG 14
WC Oncology
SC Oncology
GA CO4TO
UT WOS:000359153700001
PM 26284194
ER
PT J
AU Carrick, DM
Mehaffey, MG
Sachs, MC
Altekruse, S
Camalier, C
Chuaqui, R
Cozen, W
Das, B
Hernandez, BY
Lih, CJ
Lynch, CF
Makhlouf, H
McGregor, P
McShane, LM
Rohan, JP
Walsh, WD
Williams, PM
Gillanders, EM
Mechanic, LE
Schully, SD
AF Carrick, Danielle Mercatante
Mehaffey, Michele G.
Sachs, Michael C.
Altekruse, Sean
Camalier, Corinne
Chuaqui, Rodrigo
Cozen, Wendy
Das, Biswajit
Hernandez, Brenda Y.
Lih, Chih-Jian
Lynch, Charles F.
Makhlouf, Hala
McGregor, Paul
McShane, Lisa M.
Rohan, JoyAnn Phillips
Walsh, William D.
Williams, Paul M.
Gillanders, Elizabeth M.
Mechanic, Leah E.
Schully, Sheri D.
TI Robustness of Next Generation Sequencing on Older Formalin-Fixed
Paraffin-Embedded Tissue
SO PLOS ONE
LA English
DT Article
ID FFPE TUMOR-TISSUES; SOMATIC MUTATIONS; CANCER; SPECIMENS; GENES;
IDENTIFICATION; HETEROGENEITY; CONFIDENCE; CARCINOMA; MEDICINE
AB Next Generation Sequencing (NGS) technologies are used to detect somatic mutations in tumors and study germ line variation. Most NGS studies use DNA isolated from whole blood or fresh frozen tissue. However, formalin-fixed paraffin-embedded (FFPE) tissues are one of the most widely available clinical specimens. Their potential utility as a source of DNA for NGS would greatly enhance population-based cancer studies. While preliminary studies suggest FFPE tissue may be used for NGS, the feasibility of using archived FFPE specimens in population based studies and the effect of storage time on these specimens needs to be determined. We conducted a study to determine whether DNA in archived FFPE high-grade ovarian serous adenocarcinomas from Surveillance, Epidemiology and End Results (SEER) registries Residual Tissue Repositories (RTR) was present in sufficient quantity and quality for NGS assays. Fifty-nine FFPE tissues, stored from 3 to 32 years, were obtained from three SEER RTR sites. DNA was extracted, quantified, quality assessed, and subjected to whole exome sequencing (WES). Following DNA extraction, 58 of 59 specimens (98%) yielded DNA and moved on to the library generation step followed by WES. Specimens stored for longer periods of time had significantly lower coverage of the target region (6% lower per 10 years, 95% CI: 3-10%) and lower average read depth (40x lower per 10 years, 95% CI: 18-60), although sufficient quality and quantity of WES data was obtained for data mining. Overall, 90% (53/59) of specimens provided usable NGS data regardless of storage time. This feasibility study demonstrates FFPE specimens acquired from SEER registries after varying lengths of storage time and under varying storage conditions are a promising source of DNA for NGS.
C1 [Carrick, Danielle Mercatante; Altekruse, Sean; Gillanders, Elizabeth M.; Mechanic, Leah E.; Schully, Sheri D.] NCI, DCCPS, Rockville, MD 20850 USA.
[Mehaffey, Michele G.; Camalier, Corinne; Das, Biswajit; Lih, Chih-Jian; McGregor, Paul; Rohan, JoyAnn Phillips; Walsh, William D.; Williams, Paul M.] Leidos Biomed Res Inc, Mol Characterizat & Clin Assay Dev Lab, Frederick, MD 21702 USA.
[Mehaffey, Michele G.; Camalier, Corinne; Das, Biswajit; Lih, Chih-Jian; McGregor, Paul; Rohan, JoyAnn Phillips; Walsh, William D.; Williams, Paul M.] Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Sachs, Michael C.; Chuaqui, Rodrigo; Makhlouf, Hala; McShane, Lisa M.] NCI, DCTD, Rockville, MD 20850 USA.
[Cozen, Wendy] Univ So Calif, USC Keck Sch Med, Los Angeles, CA 90089 USA.
[Hernandez, Brenda Y.] Univ Hawaii, Ctr Canc, Honolulu, HI 96813 USA.
[Lynch, Charles F.] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA 52242 USA.
RP Carrick, DM (reprint author), NCI, DCCPS, 9609 Med Ctr Dr, Rockville, MD 20850 USA.
EM Danielle.Carrick@nih.gov
FU National Cancer Institute [N01-PC-35143, P30CA014089]; Hawaii Tumor
Registry [N01-PC-35137]; University of Hawaii Cancer Center Pathology
Shared Resource; California Department of Health Services; National
Cancer Institute, National Institutes of Health; Department of Health
and Human Services [N01-PC-2010-00035]; Centers for Disease Control and
Prevention [1U58DP000807-3]; Leidos Biomedical Research Inc.
FX This project was supported in part in Iowa by contract N01-PC-35143 from
the National Cancer Institute, and by the Hawaii Tumor Registry
(N01-PC-35137) and the University of Hawaii Cancer Center Pathology
Shared Resource. Collection of data used in this publication was
supported in part by the California Department of Health Services as
part of the statewide cancer reporting program mandated by California
Health and Safety Code Section 103885; by the National Cancer Institute,
National Institutes of Health, Department of Health and Human Services
under Contract No. N01-PC-2010-00035; and grant number 1U58DP000807-3
from the Centers for Disease Control and Prevention, and by award number
P30CA014089 from the National Cancer Institute. This study was funded by
the National Institutes of Health, National Cancer Institute. NCI and a
NCI contract laboratory (Leidos) staff members were involved in the
design of this study, lab analyses, statistical analyses, pathology
reviews, data interpretation, and writing/reviewing the manuscript. The
corresponding author, DMC, had full access to all the data in the study
and had final responsibility for the decision to submit for publication.
Leidos Biomedical Research Inc. provided support in the form of salaries
for authors MM, CC, BD, CJL, PM, JPR, WWand PMW, but did not have any
additional role in the study design, data collection and analysis,
decision to publish, or preparation of the manuscript. The specific
roles of these authors are articulated in the 'author contributions'
section.
NR 26
TC 6
Z9 6
U1 2
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 29
PY 2015
VL 10
IS 7
AR e0127353
DI 10.1371/journal.pone.0127353
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CO0JM
UT WOS:000358836800003
PM 26222067
ER
PT J
AU Huang, HW
Mullikin, JC
Hansen, NF
AF Huang, Howard W.
Mullikin, James C.
Hansen, Nancy F.
CA NISC Comparative Sequencing Progra
TI Evaluation of variant detection software for pooled next-generation
sequence data
SO BMC BIOINFORMATICS
LA English
DT Article
DE Pooling; Sequencing; Algorithms
ID HETEROGENEITY; DISCOVERY; FRAMEWORK; FORMAT
AB Background: Despite the tremendous drop in the cost of nucleotide sequencing in recent years, many research projects still utilize sequencing of pools containing multiple samples for the detection of sequence variants as a cost saving measure. Various software tools exist to analyze these pooled sequence data, yet little has been reported on the relative accuracy and ease of use of these different programs.
Results: In this manuscript we evaluate five different variant detection programs-The Genome Analysis Toolkit (GATK), CRISP, LoFreq, VarScan, and SNVer-with regard to their ability to detect variants in synthetically pooled Illumina sequencing data, by creating simulated pooled binary alignment/map (BAM) files using single-sample sequencing data from varying numbers of previously characterized samples at varying depths of coverage per sample. We report the overall runtimes and memory usage of each program, as well as each program's sensitivity and specificity to detect known true variants.
Conclusions: GATK, CRISP, and LoFreq all gave balanced accuracy of 80 % or greater for datasets with varying per-sample depth of coverage and numbers of samples per pool. VarScan and SNVer generally had balanced accuracy lower than 80 %. CRISP and LoFreq required up to four times less computational time and up to ten times less physical memory than GATK did, and without filtering, gave results with the highest sensitivity. VarScan and SNVer had generally lower false positive rates, but also significantly lower sensitivity than the other three programs.
C1 [Huang, Howard W.; Mullikin, James C.; Hansen, Nancy F.; NISC Comparative Sequencing Progra] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Hansen, NF (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA.
EM nhansen@mail.nih.gov
FU Intramural Research Program, National Human Genome Research Institute,
National Institutes of Health
FX The authors wish to acknowledge Peter S. Chines and Meghana Vemulapalli
for technical assistance in the completion of this project, and Leslie
G. Biesecker, M.D., as well as our reviewers, for constructive feedback
on this manuscript. Members of the NISC Comparative Sequencing Program
are Beatrice B. Barnabas, Robert W. Blakesley, Gerard G. Bouffard,
Shelise Y. Brooks, Holly Coleman, Jyoti G. Dayal, Lyudmila Dekhtyar,
Michael Gregory, Xiaobin Guan, Joel Han, Shi-ling Ho, Richelle Legaspi,
Quino L. Maduro, Catherine A. Masiello, Baishali Maskeri, Jennifer C.
McDowell, Casandra Montemayor, James C. Mullikin, Morgan Park, Nancy L.
Riebow, Karen Schandler, Brian Schmidt, Christina Sison, Sirintorn
Stantripop, James W. Thomas, Pamela J. Thomas, Meghana Vemulapalli, and
Alice C. Young. This work was funded by the Intramural Research Program,
National Human Genome Research Institute, National Institutes of Health.
NR 16
TC 2
Z9 2
U1 2
U2 12
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 JUL 29
PY 2015
VL 16
AR 235
DI 10.1186/s12859-015-0624-y
PG 9
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA CN6SM
UT WOS:000358564500003
PM 26220471
ER
PT J
AU Karyana, M
Kosasih, H
Samaan, G
Tjitra, E
Aman, AT
Alisjahbana, B
Fatmawati
Gasem, MH
Arif, M
Sudarmono, P
Suharto
Merati, TP
Lane, C
Siswanto
Siddiqui, S
AF Karyana, Muhammad
Kosasih, Herman
Samaan, Gina
Tjitra, Emiliana
Aman, Abu Tholib
Alisjahbana, Bachti
Fatmawati
Gasem, M. Hussein
Arif, Mansyur
Sudarmono, Pratiwi
Suharto
Merati, Tuti P.
Lane, Clifford
Siswanto
Siddiqui, Sophia
TI INA-RESPOND: a multi-centre clinical research network in Indonesia
SO HEALTH RESEARCH POLICY AND SYSTEMS
LA English
DT Editorial Material
DE Clinical; Disease; Indonesia; Infectious; Network; Research; Trial
ID VITAMIN-A; MORTALITY
AB Nationally representative observational and translational research is needed to address the public health challenges in Indonesia due to the geographic disparity, recently decentralized health system, and diverse infectious disease priorities. To accomplish this, the Indonesian Ministry of Health in collaboration with the US National Institute of Health has established INA-RESPOND (Indonesia Research Partnership on Infectious Disease) - a clinical research network comprising 9 referral hospitals, 7 medical faculties, and 2 research centres across Indonesia. The network provides a forum to conduct research at a national scale and to address scientific questions that would be difficult to address in smaller research settings. Further, it is currently conducting multi-centre research on the etiologies of fever, sepsis, and tuberculosis. There are opportunities to leverage existing network resources for other public health research needs. INA-RESPOND is an Indonesian-led network in a country with diverse population groups and public health needs which is poised to collaborate with researchers, universities, donors, and industry worldwide. This paper describes the network and its goals and values, as well as the management structure, process for collaboration, and future vision.
C1 [Karyana, Muhammad; Tjitra, Emiliana; Merati, Tuti P.; Siswanto] Minist Hlth, Ctr Appl Hlth Technol & Clin Epidemiol, NIHRD, Jakarta, Indonesia.
[Kosasih, Herman] Indonesia Res Partnership Infect Dis INA RESPOND, Jakarta, Indonesia.
[Samaan, Gina] Australia Natl Univ, Canberra, ACT, Australia.
[Aman, Abu Tholib] Univ Gadjah Mada, Fac Med, Dr Sardjito Hosp, Yogyakarta, Indonesia.
[Alisjahbana, Bachti] Univ Padjadjaran, Fac Med, Hasan Sadikin Hosp, Bandung, Indonesia.
[Fatmawati] Infect Dis Hosp, Sulianti Saroso, Jakarta, Indonesia.
[Gasem, M. Hussein] Univ Diponegoro, Fac Med, Dr Kariadi Hosp, Semarang, Indonesia.
[Arif, Mansyur] Univ Hasanudin, Fac Med, Dr Wahidin Sudirohusodo Hosp, Makassar, Indonesia.
[Sudarmono, Pratiwi] Univ Indonesia, Fac Med, Dr Cipto Mangunkusumo Hosp, Jakarta, Indonesia.
[Suharto] Univ Airlangga, Fac Med, Dr Soetomo Hosp, Surabaya, Indonesia.
[Merati, Tuti P.] Univ Udayana, Fac Med, Sanglah Hosp, Denpasar, Indonesia.
[Lane, Clifford; Siddiqui, Sophia] NIAID, US, Bethesda, MD 20892 USA.
RP Karyana, M (reprint author), Minist Hlth, Ctr Appl Hlth Technol & Clin Epidemiol, NIHRD, Jakarta, Indonesia.
EM mkaryana@gmail.com
NR 9
TC 0
Z9 0
U1 1
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1478-4505
J9 HEALTH RES POLICY SY
JI Health Res. Policy Syst.
PD JUL 29
PY 2015
VL 13
AR 34
DI 10.1186/s12961-015-0024-9
PG 6
WC Health Policy & Services
SC Health Care Sciences & Services
GA CN6RZ
UT WOS:000358563200001
PM 26219280
ER
PT J
AU Pfarr, S
Meinhardt, MW
Klee, ML
Hansson, AC
Vengeliene, V
Schonig, K
Bartsch, D
Hope, BT
Spanagel, R
Sommer, WH
AF Pfarr, Simone
Meinhardt, Marcus W.
Klee, Manuela L.
Hansson, Anita C.
Vengeliene, Valentina
Schoenig, Kai
Bartsch, Dusan
Hope, Bruce T.
Spanagel, Rainer
Sommer, Wolfgang H.
TI Losing Control: Excessive Alcohol Seeking after Selective Inactivation
of Cue-Responsive Neurons in the Infralimbic Cortex
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE alcohol self-administration; conditioned cues; Daun02 inactivation
method; medial prefrontal cortex; neuronal ensembles; reinstatement
ID MEDIAL PREFRONTAL CORTEX; NUCLEUS-ACCUMBENS SHELL; C-FOS EXPRESSION;
COCAINE-SEEKING; ETHANOL-SEEKING; ANTISENSE OLIGONUCLEOTIDE; BASOLATERAL
AMYGDALA; FEAR EXTINCTION; NERVOUS-SYSTEM; DRUG-SEEKING
AB Loss of control over drinking is a key deficit in alcoholism causally associated with malfunction of the medial prefrontal cortex (mPFC), but underlying molecular and cellular mechanisms remain unclear. Cue-induced reinstatement of alcohol seeking activates a subset of mPFC neurons in rats, identified by their common expression of the activity marker cFos and comprised of both principal and interneurons. Here, we used cFos-lacZ and pCAG-lacZ transgenic rats for activity-dependent or nonselective inactivation of neurons, respectively, which by their lacZ encoded beta-galactosidase activity convert the inactive prodrug Daun02 into the neurotoxin daunorubicin. We report that activity-dependent ablation of a neuronal ensemble in the infralimbic but not the prelimbic subregion induced excessive alcohol seeking. The targeted neuronal ensemble was specific for the cue-induced response because stress-induced reinstatement was not affected in these animals. Importantly, nonselective inactivation of infralimbic neurons, using pCAG-lacZ rats, was without functional consequence on the cue-induced reinstatement task. Thus, inhibitory control over alcohol seeking is exerted by distinct functional ensembles within the infralimbic cortex rather thanbya general inhibitory tone of this regiononthe behavioral output. This indicates a high level of functionalcompartmentation within the rat mPFC whereat many functional ensembles could coexist and interact within the same subregion.
C1 [Pfarr, Simone; Meinhardt, Marcus W.; Klee, Manuela L.; Hansson, Anita C.; Vengeliene, Valentina; Spanagel, Rainer; Sommer, Wolfgang H.] Heidelberg Univ, Med Fac Mannheim, Inst Psychopharmacol, D-68159 Heidelberg, Germany.
[Schoenig, Kai; Bartsch, Dusan] Heidelberg Univ, Med Fac Mannheim, Dept Mol Biol, D-68159 Heidelberg, Germany.
[Sommer, Wolfgang H.] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Addict Med, D-68159 Heidelberg, Germany.
[Hope, Bruce T.] NIDA, IRP, Behav Neurosci Branch, NIH, Baltimore, MD 21224 USA.
RP Meinhardt, MW (reprint author), CIMH, Sq J5, D-68159 Mannheim, Germany.
EM marcus.meinhardt@zi-mannheim.de; wolfgang.sommer@zi-mannheim.de
RI Hope, Bruce/A-9223-2010
OI Hope, Bruce/0000-0001-5804-7061
FU Deutsche Forschungsgemeinschaft [SFB636, SFB1134]; Bundesministerium fur
Bildung und Forschung within the frameworks of e:Med (BMBF) [01ZX1311A]
FX This work was supported by Deutsche Forschungsgemeinschaft center grants
(SFB636 subprojects B1 and D7 and SFB1134 subprojects B04 and B05) and
by Bundesministerium fur Bildung und Forschung within the frameworks of
e:Med (BMBF 01ZX1311A) (Spanagel et al., 2013). We thank Jennifer
Bossert and Nobuyoshi Suto for help with the cFos immunostaining
protocol; and Elisabeth Robel, Jana Zell, Sarah Meister, Sandra Dieter,
Ina Broll, Esicka Domi, and Daniel Gehrlach for technical assistance.
NR 64
TC 17
Z9 17
U1 0
U2 5
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD JUL 29
PY 2015
VL 35
IS 30
BP 10750
EP 10761
DI 10.1523/JNEUROSCI.0684-15.2015
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA CN8GO
UT WOS:000358678100010
PM 26224858
ER
PT J
AU Ma, B
Yu, J
Xie, CS
Sun, LX
Lin, SN
Ding, JH
Luo, J
Cai, HB
AF Ma, Bo
Yu, Jia
Xie, Chengsong
Sun, Lixin
Lin, Shannon
Ding, Jinhui
Luo, Jing
Cai, Huaibin
TI Toll-Like Receptors Promote Mitochondrial Translocation of Nuclear
Transcription Factor Nuclear Factor of Activated T-Cells in Prolonged
Microglial Activation
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE microglia; mitochondria; neuroinflammation; NFAT; Toll-like receptor
ID IMMUNE-RESPONSE; NFAT; NEURONS; PROTEIN; MICE; ENDOCYTOSIS; INHIBITOR;
LRRK2
AB Microglia are resident macrophages in the CNS that scavenge pathogens, dying cells, and molecules using pattern recognition Toll-like receptors (TLRs). Nuclear factor of activated T-cells (NFAT) family transcription factors also regulate inflammatory responses in microglia. However, whether there exists cross talk between TLR and NFAT signaling is unclear. Here we show that chronic activation of murine microglia by prolonged stimulation of Toll-like receptor 4 (TLR4) ligand lipopolysaccharides (LPSs) leads to unexpected translocation of NFAT1 into mitochondria. This mitochondrial import of NFAT1 is independent of calcium/calcineurin signaling. Instead, inhibition of Toll/interleukin 1 receptor domain-containing adapter-inducing interferon-beta (TRIF) pathway blocks the mitochondrial translocation of NFAT1. Functionally, inhibition of NFAT1 reduces the TRIF-mediated expression of interferon-beta and compromises the production of ATP and reactive oxygen species in LPS-treated microglia. Therefore, our findings reveal a new inflammatory signaling pathway that links TLR with NFAT in regulating cytokine production and mitochondrial activity during chronic microglial activation.
C1 [Ma, Bo; Yu, Jia; Xie, Chengsong; Sun, Lixin; Lin, Shannon; Luo, Jing; Cai, Huaibin] NIA, Transgen Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Ding, Jinhui] NIA, Bioinformat Core, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Luo, Jing] Beijing Normal Univ, Beijing Key Lab, Dept Biochem & Mol Biol, Beijing 100875, Peoples R China.
RP Cai, HB (reprint author), NIA, Transgen Sect, Neurogenet Lab, NIH, Bldg 35,Room 1A112,MSC 3707,35 Convent Dr, Bethesda, MD 20892 USA.
EM caih@mail.nih.gov
RI MA, BO/L-6502-2015
OI MA, BO/0000-0001-5922-666X
FU National Institute on Aging [AG000928, AG000929]; National Natural
Science Foundation of China [81072648, 81373389]; China Scholarship
Council
FX This work was supported in part by the intramural research programs of
the National Institute on Aging (AG000928, AG000929) and by the National
Natural Science Foundation of China (Projects 81072648 and 81373389).
The authors would like to thank members of Cai lab for providing various
supports and the China Scholarship Council for its international
exchange programs.
NR 31
TC 3
Z9 4
U1 1
U2 10
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD JUL 29
PY 2015
VL 35
IS 30
BP 10799
EP 10814
DI 10.1523/JNEUROSCI.2455-14.2015
PG 16
WC Neurosciences
SC Neurosciences & Neurology
GA CN8GO
UT WOS:000358678100014
PM 26224862
ER
PT J
AU Emanuel, EJ
Joffe, S
Grady, C
Wendler, D
Persad, G
AF Emanuel, Ezekiel J.
Joffe, Steven
Grady, Christine
Wendler, David
Persad, Govind
TI Clinical research: Should patients pay to play?
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID PARTICIPATION
AB Permitting patients to pay for participation in clinical research threatens the principles of social value and fair subject selection as well as robust clinical trial design.
C1 [Emanuel, Ezekiel J.; Joffe, Steven] Univ Penn, Dept Med Eth & Hlth Policy, Perelman Sch Med, Philadelphia, PA 19146 USA.
[Grady, Christine; Wendler, David] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
[Persad, Govind] Stanford Univ, Dept Philosophy, Stanford, CA 94305 USA.
RP Emanuel, EJ (reprint author), Univ Penn, Dept Med Eth & Hlth Policy, Perelman Sch Med, Philadelphia, PA 19146 USA.
EM vp-global@upenn.edu
NR 14
TC 2
Z9 2
U1 1
U2 5
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 JUL 29
PY 2015
VL 7
IS 298
AR 298ps16
DI 10.1126/scitranslmed.aac5204
PG 4
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA CN9AZ
UT WOS:000358739300002
PM 26223299
ER
PT J
AU Yamamoto, T
Lynch, RM
Gautam, R
Matus-Nicodemos, R
Schmidt, SD
Boswell, KL
Darko, S
Wong, P
Sheng, ZZ
Petrovas, C
McDermott, AB
Seder, RA
Keele, BF
Shapiro, L
Douek, DC
Nishimura, Y
Mascola, JR
Martin, MA
Koup, RA
AF Yamamoto, Takuya
Lynch, Rebecca M.
Gautam, Rajeev
Matus-Nicodemos, Rodrigo
Schmidt, Stephen D.
Boswell, Kristin L.
Darko, Sam
Wong, Patrick
Sheng, Zizhang
Petrovas, Constantinos
McDermott, Adrian B.
Seder, Robert A.
Keele, Brandon F.
Shapiro, Lawrence
Douek, Daniel C.
Nishimura, Yoshiaki
Mascola, John R.
Martin, Malcolm A.
Koup, Richard A.
TI Quality and quantity of T-FH cells are critical for broad antibody
development in SHIVAD8 infection
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; FOLLICULAR-HELPER-CELLS; MACAQUE B-CELLS;
NEUTRALIZING ANTIBODIES; GERMINAL CENTER; HIV-INFECTION; SINGLE-CELL;
RESPONSES; VACCINE; HYPERMUTATION
AB Broadly neutralizing antibodies (bNAbs) protect against HIV-1 infection, yet how they are generated during chronic infection remains unclear. It is known that T follicular helper (T-FH) cells are needed to promote affinitymaturation of B cells during an immune response; however, the role of T-FH during HIV-1 infection is undefined within lymph node germinal centers (GCs). We use nonhuman primates to investigate the relationship in the early stage of chronic SHIVAD8 (simian-humanimmunodeficiency virus AD8) infection between envelope (Env)-specific T-FH cells, Env-specific B cells, virus, and the generation of bNAbs during later infection. Wefound that both the frequency and quality of Envspecific T-FH cells were associated with an expansion of Env-specific immunoglobulin G-positive GC B cells and broader neutralization across HIV clades. We also found a correlation between breadth of neutralization and the degree of somatic hypermutation in Env-specific memory B cells. Finally, we observed high viral loads and greater diversity of Env sequences in rhesus macaques that developed cross-reactive neutralization as compared to those that did not. These studies highlight the importance of boosting high-quality T-FH populations as part of a robust vaccine regimen aimed at eliciting bNabs.
C1 [Yamamoto, Takuya; Matus-Nicodemos, Rodrigo; Boswell, Kristin L.; Petrovas, Constantinos; McDermott, Adrian B.; Koup, Richard A.] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Lynch, Rebecca M.; Schmidt, Stephen D.; Wong, Patrick; Mascola, John R.] NIAID, Humoral Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Gautam, Rajeev; Nishimura, Yoshiaki; Martin, Malcolm A.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Darko, Sam; Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Sheng, Zizhang; Shapiro, Lawrence] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA.
[Seder, Robert A.] NIAID, Cellular Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Keele, Brandon F.] Leidos Biomed Res Inc, AIDS & Canc Virus Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
RP Koup, RA (reprint author), NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM rkoup@mail.nih.gov
RI Schmidt, Stephen/B-5398-2012;
OI Yamamoto, Takuya/0000-0003-3753-1211
FU National Cancer Institute, NIH [HHSN261200800001E]; Intramural Research
Program of the Vaccine Research Center; Intramural Research Program of
the NIAID, NIH; Bill and Melinda Gates Foundation [OPP1032325]
FX This work was supported in part with federal funds from the National
Cancer Institute, NIH, under contract HHSN261200800001E, by the
Intramural Research Program of the Vaccine Research Center, the
Intramural Research Program of the NIAID, NIH, and Collaboration for
AIDS Vaccine Discovery grant no. OPP1032325 from the Bill and Melinda
Gates Foundation (R.A.K.).
NR 54
TC 23
Z9 23
U1 0
U2 4
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 JUL 29
PY 2015
VL 7
IS 298
AR 298ra120
DI 10.1126/scitranslmed.aab3964
PG 12
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA CN9AZ
UT WOS:000358739300006
PM 26223303
ER
PT J
AU Gupton, SL
Barzik, M
AF Gupton, Stephanie L.
Barzik, Melanie
TI Seeing Past Cellular Adaptation
SO CELL SYSTEMS
LA English
DT Editorial Material
AB Automated image analysis of unperturbed cells reveals a new sequence of events underlying protrusion of the cell membrane.
C1 [Gupton, Stephanie L.] Univ North Carolina Chapel Hill, Dept Cell Biol & Physiol, Chapel Hill, NC 27599 USA.
[Gupton, Stephanie L.] Univ North Carolina Chapel Hill, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27514 USA.
[Barzik, Melanie] NIDCD, NIH, Bethesda, MD 20892 USA.
RP Gupton, SL (reprint author), Univ North Carolina Chapel Hill, Dept Cell Biol & Physiol, Chapel Hill, NC 27599 USA.; Gupton, SL (reprint author), Univ North Carolina Chapel Hill, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27514 USA.
EM sgupton@email.unc.edu
OI Barzik, Melanie/0000-0003-3003-1281
FU National Institutes of Health [GM108970]; NIH - National Institute on
Deafness and Other Communication Disorders (NIDCD) [1 Z01 DC000039-17]
FX This work was supported by the National Institutes of Health: GM108970
(S.L.G.). This work was also supported by NIH intramural funds from the
National Institute on Deafness and Other Communication Disorders (NIDCD)
1 Z01 DC000039-17 to T.B. Friedman (Laboratory of Molecular Genetics,
NIDCD, NIH).
NR 9
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2405-4712
EI 2405-4720
J9 CELL SYST
JI Cell Syst.
PD JUL 29
PY 2015
VL 1
IS 1
BP 16
EP 17
DI 10.1016/j.cels.2015.07.002
PG 2
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA V47AT
UT WOS:000209925400007
PM 26301261
ER
PT J
AU Sheu, HL
Boopalachandran, P
Kim, S
Laane, J
AF Sheu, Hong-Li
Boopalachandran, Praveenkumar
Kim, Sunghwan
Laane, Jaan
TI Infrared, Raman, and ultraviolet absorption spectra and theoretical
calculations and structure of 2,3,5,6-tetrafluoropyridine in its ground
and excited electronic states
SO CHEMICAL PHYSICS
LA English
DT Article
DE Vibrational spectra; Ultraviolet absorption spectra; Electronic excited
state; Molecular structure; 2,3,5,6-Tetrafluoropyridine
ID WAVE-FUNCTIONS; DIPOLE-MOMENT; PYRIDINE; DENSITY
AB Infrared and Raman spectra of 2,3,5,6-tetrafluoropyridine (TFPy) were recorded and vibrational frequencies were assigned for its S-0 electronic ground states. Ab initio and density functional theory (DFT) calculations were used to complement the experimental work. The lowest electronic excited state of this molecule was investigated with ultraviolet absorption spectroscopy and theoretical CASSCF calculations. The band origin was found to be at 35,704.6 cm(-1) in the ultraviolet absorption spectrum. A slightly puckered structure with a barrier to planarity of 30 cm(-1) was predicted by CASSCF calculations for the S-1(pi, pi*) state. Lower frequencies for the out-of-plane ring bending vibrations for the electronic excited state result from the weaker p bonding within the pyridine ring. (C) 2015 Elsevier B.V. All rights reserved.
C1 [Sheu, Hong-Li; Boopalachandran, Praveenkumar; 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@chem.tamu.edu
RI Kim, Sunghwan/A-6738-2008; Sheu, Hong-Li/B-4889-2016;
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
NIH, National Library of Medicine; National Science Foundation
[CHE-0541587]; Biowulf Linux cluster at the National Institutes of
Health, Bethesda, MD
FX The authors wish to thank the Robert A. Welch Foundation (Grant A-0396)
for financial support. This research was also supported in part by the
Intramural Research Program of the NIH, National Library of Medicine.
Calculations were carried out on the Texas A&M Department of Chemistry
Medusa computer system funded by the National Science Foundation, Grant
No. CHE-0541587, and the Biowulf Linux cluster at the National
Institutes of Health, Bethesda, MD (http://biowulf.nih.gov).
NR 21
TC 1
Z9 1
U1 0
U2 17
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0301-0104
EI 1873-4421
J9 CHEM PHYS
JI Chem. Phys.
PD JUL 29
PY 2015
VL 456
BP 28
EP 33
DI 10.1016/j.chemphys.2015.04.011
PG 6
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA CK3FP
UT WOS:000356102300005
PM 26113767
ER
PT J
AU Barrett, JS
Hirankarn, S
Holford, N
Hammer, GB
Drover, DR
Cohane, C
Anderson, B
Dombrowski, E
Reece, T
Zajicek, A
Schulman, SR
AF Barrett, Jeffrey S.
Hirankarn, Sarapee
Holford, Nick
Hammer, Gregory B.
Drover, David R.
Cohane, CarolA.
Anderson, Brian
Dombrowski, Erin
Reece, Tammy
Zajicek, Anne
Schulman, Scott R.
TI A hemodynamic model to guide blood pressure control during deliberate
hypotension with sodium nitroprusside in children
SO FRONTIERS IN PHARMACOLOGY
LA English
DT Article
DE sodium nitroprusside; hemodynamics; models; biological; pediatrics;
hypotension; controlled
ID PHARMACOKINETICS; METABOLISM; SIZE
AB Sodium nitroprusside (SNP) has been widely used to control blood pressure in infants and children. The goals of this analysis were to develop models that describe the hemodynamic response to SNP dosing in pediatric patients; examine sources of variation in dose-response, defining age, and size dependencies; and determine vulnerable populations or patient subtypes that may elicit dosing modifications. A multi-center, randomized, double-blinded, parallel-group, dose-ranging, effect-controlled study, followed by an open-label dose titration of an intravenous infusion of SNP was undertaken in 203 pediatric subjects, who required deliberate hypotension or controlled normotension during anesthesia. A total of 3464 MAP measurements collected from 202 patients during the study's blinded phase, including baseline measurements up to 6 min prior to the blinded were available for analysis. A population K-PD model was developed with a one-compartment model assumed for SNP. Size differences in CL and V of the effect compartment were described using theory-based allometry. An inhibitory sigmoidal E-max model was used to describe the effect of SNP. A power function of age was used to describe age-related differences in baseline MAP. A mixture model of two groups with low and high EC50 was used to explain variability in MAP response. Change in MAP was characterized by a linear disease progression slope during the blinded phase. In the final population model, CL and V increased with weight, and baseline MAP increased with age. The effect compartment half-life of SNP was 13.4 min. The infusion rate producing 50% of E-max (ER50) at steady state for high EC50, was 0.34 mu g/kg/min and for low EC50 0.103 mu g/kg/min. The K-PD model well-describes initial dosing of SNP under controlled circumstances; model-based dosing guidance agrees with current practice. An initial titration strategy supported via algorithm-based feedback should improve maintenance of target MAP.
C1 [Barrett, Jeffrey S.; Hirankarn, Sarapee; Dombrowski, Erin] Univ Penn, Childrens Hosp Philadelphia, Clin Pharmacol & Therapeut Div, Sch Med, Philadelphia, PA 19104 USA.
[Barrett, Jeffrey S.; Hirankarn, Sarapee; Dombrowski, Erin] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA.
[Holford, Nick] Univ Auckland, Dept Pharmacol & Clin Pharmacol & Anesthesia, Auckland 1, New Zealand.
[Holford, Nick; Anderson, Brian] Univ Auckland, Dept Anesthesia, Auckland 1, New Zealand.
[Hammer, Gregory B.; Drover, David R.; Cohane, CarolA.] Stanford Univ, Sch Med, Dept Anesthesiol Perioperat & Pain Med, Stanford, CA 94305 USA.
[Reece, Tammy; Schulman, Scott R.] Univ Durham, Med Ctr, Duke Clin Res Inst, Durham, NC USA.
[Zajicek, Anne] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Barrett, JS (reprint author), Univ Penn, Childrens Hosp Philadelphia, Dept Pediat, Perelman Sch Med,Abramson Res Ctr, Colket Translat Res Bldg,Room 1210, Philadelphia, PA 19104 USA.
EM jeffrey.barrett@sanofi.com
OI Holford, Nick/0000-0002-4031-2514
FU NICHD, Rockville, Maryland [NO1-HD-4-3385]
FX NO1-HD-4-3385 (NICHD, Rockville, Maryland).
NR 17
TC 0
Z9 0
U1 1
U2 2
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1663-9812
J9 FRONT PHARMACOL
JI Front. Pharmacol.
PD JUL 28
PY 2015
VL 6
AR 151
DI 10.3389/fphar.2015.00151
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CW9PA
UT WOS:000365329500001
PM 26283961
ER
PT J
AU Shi, CH
Song, B
Luo, HY
Mao, CY
Shang, DD
Cao, Y
Sun, SL
Wu, J
Zhuang, ZP
Xu, YM
AF Shi, Chang-he
Song, Bo
Luo, Hai-yang
Mao, Cheng-yuan
Shang, Dan-dan
Cao, Yuan
Sun, Shi-lei
Wu, Jun
Zhuang, Zheng-ping
Xu, Yu-ming
TI RECESSIVE HEREDITARY MOTOR AND SENSORY NEUROPATHY CAUSED BY IGHMBP2 GENE
MUTATION
SO NEUROLOGY
LA English
DT Editorial Material
ID RESPIRATORY-DISTRESS TYPE-1; SPINAL MUSCULAR-ATROPHY; DISEASE
AB Hereditary motor and sensory neuropathy (HMSN), also known as Charcot-Marie-Tooth disease (CMT), is a genetically heterogeneous disorder that affects both sensory and motor peripheral nerves. HMSN is characterized by distal and symmetric muscle atrophy in the lower limbs and hands, foot abnormalities, and distal sensory loss. It is associated with more than 50 causative genes or loci; however, the genetic cause remains undetermined in almost 50% of HMSN cases.
C1 [Shi, Chang-he; Song, Bo; Luo, Hai-yang; Mao, Cheng-yuan; Shang, Dan-dan; Cao, Yuan; Sun, Shi-lei; Wu, Jun; Xu, Yu-ming] Zhengzhou Univ, Dept Neurol, Affiliated Hosp 1, Zhengzhou 450052, Henan, Peoples R China.
[Zhuang, Zheng-ping] NINDS, Surg Neurol Branch, Bethesda, MD 20892 USA.
RP Xu, YM (reprint author), Zhengzhou Univ, Dept Neurol, Affiliated Hosp 1, Zhengzhou 450052, Henan, Peoples R China.
EM xuyuming@zzu.edu.cn
NR 7
TC 3
Z9 3
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD JUL 28
PY 2015
VL 85
IS 4
BP 383
EP 384
DI 10.1212/WNL.0000000000001747
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA CO7MK
UT WOS:000359343300013
PM 26136520
ER
PT J
AU Gartner, V
McGuire, PJ
Lee, PR
AF Gartner, Valerie
McGuire, Peter J.
Lee, Paul R.
TI Child Neurology: Medium-chain acyl-coenzyme A dehydrogenase deficiency
SO NEUROLOGY
LA English
DT Article
ID ACID BETA-OXIDATION; DIAGNOSIS
AB Medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency (MCADD) is an autosomal recessive inherited fatty acid oxidation disorder. In MCADD, mitochondria cannot process medium-chain fatty acids via the -oxidation pathway because of a lack of MCAD. While patients may be asymptomatic during the prenatal or immediate postnatal periods, patients will experience decompensation due to profound hypoglycemia during fasting or illness with often rapid progression to encephalopathy, seizures, coma, or death. Newborn screening tests can identify virtually all new cases of MCADD in a cost-effective manner, often with reflex follow-up targeted mutation analysis for the 2 most common alleles. With appropriate monitoring, prevention through avoidance of fasting, and intervention during an impending crisis, patients with MCADD can survive into adulthood with no neurologic sequelae.
C1 [Gartner, Valerie; McGuire, Peter J.; Lee, Paul R.] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Lee, PR (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA.
EM paul.lee@nih.gov
FU Intramural Program of the National Human Genome Research Institute
FX Supported by the Intramural Program of the National Human Genome
Research Institute.
NR 10
TC 0
Z9 0
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD JUL 28
PY 2015
VL 85
IS 4
BP E37
EP E40
DI 10.1212/WNL.0000000000001786
PG 4
WC Clinical Neurology
SC Neurosciences & Neurology
GA CO7ML
UT WOS:000359343400005
PM 26215884
ER
PT J
AU Eysteinsdottir, T
Halldorsson, TI
Thorsdottir, I
Sigurdsson, G
Sigurdsson, S
Harris, T
Launer, LJ
Gudnason, V
Gunnarsdottir, I
Steingrimsdottir, L
AF Eysteinsdottir, Tinna
Halldorsson, Thorhallur I.
Thorsdottir, Inga
Sigurdsson, Gunnar
Sigurdsson, Sigurdur
Harris, Tamara
Launer, Lenore J.
Gudnason, Vilmundur
Gunnarsdottir, Ingibjorg
Steingrimsdottir, Laufey
TI Cod liver oil consumption at different periods of life and bone mineral
density in old age
SO BRITISH JOURNAL OF NUTRITION
LA English
DT Article
DE Cod liver oil; Lifelong consumption; Bone density; Elderly individuals
ID VITAMIN-D SUPPLEMENTATION; GENE/ENVIRONMENT SUSCEPTIBILITY-REYKJAVIK;
FOOD FREQUENCY QUESTIONNAIRE; POSTMENOPAUSAL WOMEN; OSTEOPOROTIC
FRACTURES; PARATHYROID-HORMONE; MILK CONSUMPTION; DIETARY-INTAKE;
ELDERLY-WOMEN; HIP FRACTURE
AB Cod liver oil is a traditional source of vitamin D in Iceland, and regular intake is recommended partly for the sake of bone health. However, the association between lifelong consumption of cod liver oil and bone mineral density (BMD) in old age is unclear. The present study attempted to assess the associations between intake of cod liver oil in adolescence, midlife, and old age, and hip BMD in old age, as well as associations between cod liver oil intake in old age and serum 25-hydroxyvitamin D (25(OH)D) concentration. Participants of the Age, Gene/Environment Susceptibility-Reykjavik Study (age 66-96 years; n 4798), reported retrospectively cod liver oil intake during adolescence and midlife, as well as the one now in old age, using a validated FFQ. BMD of femoral neck and trochanteric region was measured by volumetric quantitative computed tomography, and serum 25(OH)D concentration was measured by means of a direct, competitive chemiluminescence immunoassay. Associations were assessed using linear regression models. No significant association was seen between retrospective cod liver oil intake and hip BMD in old age. Current intake of aged men was also not associated with hip BMD, while aged women with daily intakes had z-scores on average 0.1 higher, compared with those with an intake of < once/week. Although significant, this difference is small, and its clinical relevance is questionable. Intake of aged participants was positively associated with serum 25(OH)D: individuals with intakes of < once/week, one to six time(s)/week and daily intake had concentrations of approximately 40, 50 and 60 nmol/l respectively (P for trend <0.001).
C1 [Eysteinsdottir, Tinna; Halldorsson, Thorhallur I.; Thorsdottir, Inga; Gunnarsdottir, Ingibjorg; Steingrimsdottir, Laufey] Univ Iceland, Unit Nutr Res, IS-101 Reykjavik, Iceland.
[Eysteinsdottir, Tinna; Halldorsson, Thorhallur I.; Thorsdottir, Inga; Sigurdsson, Gunnar; Gudnason, Vilmundur; Gunnarsdottir, Ingibjorg; Steingrimsdottir, Laufey] Landspitali Natl Univ Hosp, IS-101 Reykjavik, Iceland.
[Halldorsson, Thorhallur I.; Thorsdottir, Inga; Gunnarsdottir, Ingibjorg; Steingrimsdottir, Laufey] Univ Iceland, Sch Hlth Sci, Fac Food Sci & Human Nutr, IS-101 Reykjavik, Iceland.
[Sigurdsson, Gunnar; Sigurdsson, Sigurdur; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Sigurdsson, Gunnar; Gudnason, Vilmundur] Univ Iceland, Sch Hlth Sci, Fac Med, IS-101 Reykjavik, Iceland.
[Harris, Tamara; Launer, Lenore J.] NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, Bethesda, MD 20892 USA.
RP Steingrimsdottir, L (reprint author), Univ Iceland, Unit Nutr Res, Eiriksgata 29, IS-101 Reykjavik, Iceland.
EM laufey@hi.is
RI Gudnason, Vilmundur/K-6885-2015; Gunnarsdottir, Ingibjorg/L-9371-2015;
Halldorsson, Tohrhallur/M-1823-2015;
OI Gudnason, Vilmundur/0000-0001-5696-0084; Halldorsson,
Tohrhallur/0000-0001-5115-0162; Gunnarsdottir,
Ingibjorg/0000-0001-9447-8627
FU Icelandic Research Fund for Graduate Students [RAN090310-0796];
Nordforsk NCoE Program HELGA; NIH [N01-AG-12100]; Intramural Research
Program of the National Institute on Aging; Icelandic Heart Association;
Icelandic Parliament
FX T. E. received funding from the Icelandic Research Fund for Graduate
Students (RAN090310-0796) and the Nordforsk NCoE Program HELGA.; The
AGES-Reykjavik Study was funded by NIH (contract no. N01-AG-12100), the
Intramural Research Program of the National Institute on Aging, and by
the Icelandic Heart Association and the Icelandic Parliament.
NR 42
TC 1
Z9 1
U1 0
U2 5
PU CAMBRIDGE UNIV PRESS
PI CAMBRIDGE
PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND
SN 0007-1145
EI 1475-2662
J9 BRIT J NUTR
JI Br. J. Nutr.
PD JUL 28
PY 2015
VL 114
IS 2
BP 248
EP 256
DI 10.1017/S0007114515001397
PG 9
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA CO3TZ
UT WOS:000359084200010
PM 26079168
ER
PT J
AU Wu, J
Cai, BW
Sun, WX
Huang, RL
Liu, XQ
Lin, M
Pattaradilokrat, S
Martin, S
Qi, YW
Nair, SC
Bolland, S
Cohen, JI
Austin, CP
Long, CA
Myers, TG
Wang, RF
Su, XZ
AF Wu, Jian
Cai, Baowei
Sun, Wenxiang
Huang, Ruili
Liu, Xueqiao
Lin, Meng
Pattaradilokrat, Sittiporn
Martin, Scott
Qi, Yanwei
Nair, Sethu C.
Bolland, Silvia
Cohen, Jeffrey I.
Austin, Christopher P.
Long, Carole A.
Myers, Timothy G.
Wang, Rong-Fu
Su, Xin-zhuan
TI Genome-wide Analysis of Host-Plasmodium yoelii Interactions Reveals
Regulators of the Type I Interferon Response
SO CELL REPORTS
LA English
DT Article
ID QUANTITATIVE TRAIT LOCI; INNATE IMMUNE-RESPONSES; GMP-AMP SYNTHASE;
EXPRESSION; CELL; RECOGNITION; FALCIPARUM; INFECTION; PARASITES; SENSOR
AB Invading pathogens trigger specific host responses, an understanding of which might identify genes that function in pathogen recognition and elimination. In this study, we performed trans-species expression quantitative trait locus (ts-eQTL) analysis using genotypes of the Plasmodium yoelii malaria parasite and phenotypes of mouse gene expression. We significantly linked 1,054 host genes to parasite genetic loci (LOD score >= 3.0). Using LOD score patterns, which produced results that differed from direct expression-level clustering, we grouped host genes that function in related pathways, allowing functional prediction of unknown genes. As a proof of principle, 14 of 15 randomly selected genes predicted to function in type I interferon (IFN-I) responses were experimentally validated using overexpression, small hairpin RNA knockdown, viral infection, and/or infection of knockout mice. This study demonstrates an effective strategy for studying gene function, establishes a functional gene database, and identifies regulators in IFN-I pathways.
C1 [Wu, Jian; Pattaradilokrat, Sittiporn; Qi, Yanwei; Nair, Sethu C.; Long, Carole A.; Su, Xin-zhuan] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
[Cai, Baowei; Qi, Yanwei; Su, Xin-zhuan] Xiamen Univ, Sch Life Sci, Innovat Ctr Cell Signaling Network, State Key Lab Cellular Stress Biol, Xiamen 361005, Fujian, Peoples R China.
[Cai, Baowei; Lin, Meng; Wang, Rong-Fu] Houston Methodist Res Inst, Ctr Inflammat & Epigenet, Houston, TX 77030 USA.
[Sun, Wenxiang; Bolland, Silvia] NIAID, Lab Immunogenet, NIH, Bethesda, MD 20892 USA.
[Huang, Ruili; Martin, Scott; Austin, Christopher P.] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
[Liu, Xueqiao; Cohen, Jeffrey I.] NIAID, Lab Infect Dis, NIH, Bethesda, MD 20892 USA.
[Pattaradilokrat, Sittiporn] Chulalongkorn Univ, Dept Biol, Fac Sci, Bangkok 10330, Thailand.
[Myers, Timothy G.] NIAID, Genom Technol Sect, Res Technol Branch, NIH, Bethesda, MD 20892 USA.
RP Wang, RF (reprint author), Houston Methodist Res Inst, Ctr Inflammat & Epigenet, Houston, TX 77030 USA.
EM rwang3@houstonmethodist.org; xsu@niaid.nih.gov
RI Wu, Jian/K-2038-2015;
OI Wu, Jian/0000-0001-8011-9551; Su, Xinzhuan/0000-0003-3246-3248
FU Division of Intramural Research at the National Institute of Allergy and
Infectious Diseases (NIAID); National Center for Advancing Translational
Sciences (NCATS); National Institutes of Health (NIH); Project 111 of
the State Bureau of Foreign Experts and Ministry of Education of China
[B06016]; National Cancer Institute, NIH [R01CA090327, R01CA101795];
Chinese Scholar Council
FX This work was supported by the Division of Intramural Research at the
National Institute of Allergy and Infectious Diseases (NIAID) and the
National Center for Advancing Translational Sciences (NCATS), National
Institutes of Health (NIH), by Project 111 of the State Bureau of
Foreign Experts and Ministry of Education of China (B06016), and
supported in part by grants from the National Cancer Institute, NIH
(R01CA090327 and R01CA101795) to R.-F.W.B.C. and M.L. were supported in
part by the Chinese Scholar Council. We thank Dr. J.S. Verbeek for the
Fcgr1 KO mice and Cindy Clark of the NIH Library for editing.
NR 41
TC 4
Z9 4
U1 1
U2 4
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2211-1247
J9 CELL REP
JI Cell Reports
PD JUL 28
PY 2015
VL 12
IS 4
BP 661
EP 672
DI 10.1016/j.celrep.2015.06.058
PG 12
WC Cell Biology
SC Cell Biology
GA CN9BZ
UT WOS:000358742300012
PM 26190101
ER
PT J
AU Arem, H
Park, Y
Felix, AS
Zervoudakis, A
Brinton, LA
Matthews, CE
Gunter, MJ
AF Arem, H.
Park, Y.
Felix, A. S.
Zervoudakis, A.
Brinton, L. A.
Matthews, C. E.
Gunter, M. J.
TI Reproductive and hormonal factors and mortality among women with
colorectal cancer in the NIH-AARP Diet and Health Study
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE reproductive factors; colorectal cancer; epidemiology; hormonal factors;
mortality
ID POSTMENOPAUSAL WOMEN; REPLACEMENT THERAPY; COLON-CANCER; ESTROGEN;
SURVIVAL; RISK; COHORT; PROGESTIN; TRIAL
AB Background: Although use of menopausal hormone therapy (MHT) and some reproductive factors have been associated with colorectal cancer (CRC) risk, relations between these factors and survival after CRC diagnosis are unclear.
Methods: Among 2053 post-menopausal women diagnosed with incident CRC in the NIH-AARP Diet and Health Study, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) using multivariable Cox proportional hazards regression to test associations between oral contraceptive (OC) use, menarche age, age at first birth, parity, menopausal age, and MHT use with all-cause and CRC-specific mortality.
Results: There were 759 deaths (332 CRC-related deaths) over a median follow-up of 7.7 years. We observed no statistically significant associations between OC use, menarche age, age at first birth, parity, menopausal age, and mortality. Compared with never MHT use, former use was not associated with mortality, but we found an inverse association among baseline current users, for both all-cause (HR = 0.79, 95% CI 0.66-0.94) and CRC mortality (0.76, 0.59-0.99).
Conclusion: Future studies should further focus on the mechanisms by which exogenous oestrogen exposure might affect tumour progression and CRC survival.
C1 [Arem, H.; Felix, A. S.; Brinton, L. A.; Matthews, C. E.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Park, Y.] Washington Univ, Sch Med St Louis, Div Publ Hlth Sci, St Louis, MO 63110 USA.
[Zervoudakis, A.] Winthrop Univ Hosp, Div Hematol Oncol, Mineola, NY 11501 USA.
[Gunter, M. J.] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London W2 1PG, England.
RP Arem, H (reprint author), NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
EM Aremhe2@mail.nih.gov
RI Felix, Ashley/A-3240-2016
FU Intramural NIH HHS
NR 25
TC 1
Z9 1
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
EI 1532-1827
J9 BRIT J CANCER
JI Br. J. Cancer
PD JUL 28
PY 2015
VL 113
IS 3
BP 562
EP 568
DI 10.1038/bjc.2015.224
PG 7
WC Oncology
SC Oncology
GA CN8FI
UT WOS:000358674300026
PM 26103572
ER
PT J
AU Forlani, G
Bertazzini, M
Zarattini, M
Funck, D
Ruszkowski, M
Nocek, B
AF Forlani, Giuseppe
Bertazzini, Michele
Zarattini, Marco
Funck, Dietmar
Ruszkowski, Milosz
Nocek, Boguslaw
TI Functional properties and structural characterization of rice
delta(1)-pyrroline-5-carboxylate reductase
SO FRONTIERS IN PLANT SCIENCE
LA English
DT Article
DE proline synthesis; P5C reductase; enzyme properties; substrate
ambiguity; cation and anion effects; product inhibition; oligomeric
structure
ID ORNITHINE-DELTA-AMINOTRANSFERASE; PLANT P5C REDUCTASE;
PYRROLINE-5-CARBOXYLATE REDUCTASE; PROLINE SYNTHESIS; HYPERSENSITIVE
RESPONSE; STREPTOCOCCUS-PYOGENES; ARABIDOPSIS-THALIANA; CULTURED-CELLS;
DEHYDROGENASE; STRESS
AB The majority of plant species accumulate high intracellular levels of proline to cope with hyperosmotic stress conditions. Proline synthesis from glutamate is tightly regulated at both the transcriptional and the translational levels, yet little is known about the mechanisms for post-translational regulation of the enzymatic activities involved. The gene coding in rice (Oryza sativa L.) for delta(1)-pyrroline-5-carboxylate (P5C) reductase, the enzyme that catalyzes the second and final step in this pathway, was isolated and expressed in Escherichia coli. The structural and functional properties of the affinity-purified protein were characterized. As for most species, rice P5C reductase was able to use in vitro either NADH or NADPH as the electron donor. However, strikingly different effects of cations and anions were found depending on the pyridine nucleotide used, namely inhibition of NADH-dependent activity and stimulation of NADPH-dependent activity. Moreover, physiological concentrations of proline and NADP(+) were strongly inhibitory for the NADH-dependent reaction, whereas the NADPH-dependent activity was mildly affected. Our results suggest that only NADPH may be used in vivo and that stress-dependent variations in ion homeostasis and NADPH/NADP(+) ratio could modulate enzyme activity, being functional in promoting proline accumulation and potentially also adjusting NADPH consumption during the defense against hyperosmotic stress. The apparent molecular weight of the native protein observed in size exclusion chromatography indicated a high oligomerization state. We also report the first crystal structure of a plant P5C reductase at 3.40-angstrom resolution, showing a decameric quaternary assembly. Based on the structure, it was possible to identify dynamic structural differences among rice, human, and bacterial enzymes.
C1 [Forlani, Giuseppe; Bertazzini, Michele; Zarattini, Marco] Univ Ferrara, Dept Life Sci & Biotechnol, Lab Plant Physiol & Biochem, I-44121 Ferrara, Italy.
[Bertazzini, Michele; Funck, Dietmar] Univ Konstanz, Dept Biol, Plant Physiol & Biochem, Constance, Germany.
[Ruszkowski, Milosz] NCI, Synchrotron Radiat Res Sect, Macromol Crystallog Lab, Argonne Natl Lab, Argonne, IL USA.
[Nocek, Boguslaw] Argonne Natl Lab, Biosci Div, Argonne, IL 60439 USA.
RP Forlani, G (reprint author), Univ Ferrara, Dept Life Sci & Biotechnol, Lab Plant Physiol & Biochem, Via Luigi Borsari 46, I-44121 Ferrara, Italy.
EM flg@unife.it
RI Forlani, Giuseppe/B-7869-2009
OI Forlani, Giuseppe/0000-0003-2598-5718
FU AGER Foundation in the frame of the RISINNOVA project [2010-2369];
University of Konstanz; Intramural Research Program of the NCI, Center
for Cancer Research; US Department of Energy, Office of Science, Office
of Basic Energy Sciences [W-31-109-Eng-38]; DAAD (German Academic
Exchange Service) fellowship
FX This work was funded by AGER Foundation in the frame of the RISINNOVA
project, grant # 2010-2369. Partial support from the University of
Konstanz and the Intramural Research Program of the NCI, Center for
Cancer Research, is also gratefully acknowledged. Diffraction data were
collected at the SER-CAT beamline 22-ID at the Advanced Photon Source,
Argonne National Laboratory. Use of the Advanced Photon Source was
funded by the US Department of Energy, Office of Science, Office of
Basic Energy Sciences under Contract No. W-31-109-Eng-38. MB was the
recipient of a DAAD (German Academic Exchange Service) fellowship
supporting a stage in DF's laboratory.
NR 65
TC 3
Z9 3
U1 6
U2 15
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1664-462X
J9 FRONT PLANT SCI
JI Front. Plant Sci.
PD JUL 28
PY 2015
VL 6
AR 565
DI 10.3389/fpls.2015.00565
PG 13
WC Plant Sciences
SC Plant Sciences
GA CN8VW
UT WOS:000358724700001
PM 26284087
ER
PT J
AU Zhao, WT
Liu, JW
Xu, RX
Zhang, C
Pang, Q
Chen, X
Liu, SF
Hong, LX
Yuan, J
Li, XT
Chen, YX
Li, J
Su, XZ
AF Zhao, Wenting
Liu, Jianwen
Xu, Ruixue
Zhang, Cui
Pang, Qin
Chen, Xin
Liu, Shengfa
Hong, Lingxian
Yuan, Jing
Li, Xiaotong
Chen, Yixin
Li, Jian
Su, Xin-zhuan
TI The Gametocytes of Leucocytozoon sabrazesi Infect Chicken Thrombocytes,
Not Other Blood Cells
SO PLOS ONE
LA English
DT Article
ID BONE-MARROW; PLASMODIUM; PREVALENCE; PARASITES; BIRDS; AGGREGATION;
PHAGOCYTES; MICROSCOPY; SMITHI; VITRO
AB Leucocytozoon parasites infect a large number of avian hosts, including domestic chicken, and cause significant economical loss to the poultry industry. Although the transmission stages of the parasites were observed in avian blood cells more than a century ago, the specific host cell type(s) that the gametocytes infect remain uncertain. Because all the avian blood cells, including red blood cells (RBCs), are nucleated, and the developing parasites dramatically change the morphology of the infected host cells, it has been difficult to identify Leucocytozoon infected host cell(s). Here we use cell-type specific antibodies to investigate the identities of the host cells infected by Leucocytozoon sabrazesi gametocytes. Anti-RBC antibodies stained RBCs membrane strongly, but not the parasite-infected cells, ruling out the possibility of RBCs being the infected host cells. Antibodies recognizing various leukocytes including heterophils, monocytes, lymphocytes, and macrophages did not stain the infected cells either. Antisera raised against a peptide of the parasite cytochrome B (CYTB) stained parasite-infected cells and some leukocytes, particularly cells with a single round nucleus as well as clear/pale cytoplasm suggestive of thrombocytes. Finally, a monoclonal antibody known to specifically bind chicken thrombocytes also stained the infected cells, confirming that L. sabrazesi gametocytes develop within chicken thrombocytes. The identification of L. sabrazesi infected host cell solves a long unresolved puzzle and provides important information for studying parasite invasion of host cells and for developing reagents to interrupt parasite transmission.
C1 [Zhao, Wenting; Liu, Jianwen; Xu, Ruixue; Zhang, Cui; Pang, Qin; Chen, Xin; Liu, Shengfa; Hong, Lingxian; Yuan, Jing; Li, Xiaotong; Chen, Yixin; Li, Jian; Su, Xin-zhuan] Xiamen Univ, State Key Lab Cellular Stress Biol, Innovat Ctr Cell Signaling Network, Sch Life Sci, Xiamen 361005, Fujian, Peoples R China.
[Chen, Yixin] Xiamen Univ, Natl Inst Diagnost & Vaccine Dev Infect Dis, Sch Publ Hlth, Xiamen 361005, Fujian, Peoples R China.
[Su, Xin-zhuan] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
RP Li, J (reprint author), Xiamen Univ, State Key Lab Cellular Stress Biol, Innovat Ctr Cell Signaling Network, Sch Life Sci, Xiamen 361005, Fujian, Peoples R China.
EM jianli_204@xmu.edu.cn; xsu@niaid.nih.gov
OI Su, Xinzhuan/0000-0003-3246-3248
FU National Natural Science Foundation of China [81220108019, 81271858,
81201324]; Project 111 of the State Bureau of Foreign Experts and
Ministry of Education of China [B06016]; Division of Intramural
Research, National Institute of Allergy and Infectious Diseases,
National Institutes of Health
FX This work was supported by the National Natural Science Foundation of
China #81220108019, 81271858, and #81201324, by Project 111 of the State
Bureau of Foreign Experts and Ministry of Education of China (B06016),
and by the Division of Intramural Research, 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 33
TC 2
Z9 2
U1 0
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 28
PY 2015
VL 10
IS 7
AR e0133478
DI 10.1371/journal.pone.0133478
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN7ED
UT WOS:000358595900032
PM 26218846
ER
PT J
AU Dodge, KA
Malone, PS
Lansford, JE
Sorbring, E
Skinner, AT
Tapanya, S
Tirado, LMU
Zelli, A
Alampay, LP
Al-Hassan, SM
Bacchini, D
Bombi, AS
Bornstein, MH
Chang, L
Deater-Deckard, K
Di Giunta, L
Oburu, P
Pastorelli, C
AF Dodge, Kenneth A.
Malone, Patrick S.
Lansford, Jennifer E.
Sorbring, Emma
Skinner, Ann T.
Tapanya, Sombat
Uribe Tirado, Liliana Maria
Zelli, Arnaldo
Pena Alampay, Liane
Al-Hassan, Suha M.
Bacchini, Dario
Bombi, Anna Silvia
Bornstein, Marc H.
Chang, Lei
Deater-Deckard, Kirby
Di Giunta, Laura
Oburu, Paul
Pastorelli, Concetta
TI Hostile attributional bias and aggressive behavior in global context
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE aggressive behavior; cultural differences; hostile attribution;
interpersonal conflict; social cognition
ID INTERVENTION; CHILDREN; SOCIALIZATION; PERSONALITY
AB We tested a model that children's tendency to attribute hostile intent to others in response to provocation is a key psychological process that statistically accounts for individual differences in reactive aggressive behavior and that this mechanism contributes to global group differences in children's chronic aggressive behavior problems. Participants were 1,299 children (mean age at year 1 = 8.3 y; 51% girls) from 12 diverse ecological-context groups in nine countries worldwide, followed across 4 y. In year 3, each child was presented with each of 10 hypothetical vignettes depicting an ambiguous provocation toward the child and was asked to attribute the likely intent of the provocateur (coded as benign or hostile) and to predict his or her own behavioral response (coded as nonaggression or reactive aggression). Mothers and children independently rated the child's chronic aggressive behavior problems in years 2, 3, and 4. In every ecological group, in those situations in which a child attributed hostile intent to a peer, that child was more likely to report that he or she would respond with reactive aggression than in situations when that same child attributed benign intent. Across children, hostile attributional bias scores predicted higher mother-and child-rated chronic aggressive behavior problems, even controlling for prior aggression. Ecological group differences in the tendency for children to attribute hostile intent statistically accounted for a significant portion of group differences in chronic aggressive behavior problems. The findings suggest a psychological mechanism for group differences in aggressive behavior and point to potential interventions to reduce aggressive behavior.
C1 [Dodge, Kenneth A.; Malone, Patrick S.; Lansford, Jennifer E.; Skinner, Ann T.] Duke Univ, Ctr Child & Family Policy, Durham, NC 27708 USA.
[Sorbring, Emma] Univ West, Child & Youth Studies, SE-46100 Tollhattan, Sweden.
[Tapanya, Sombat] Chiang Mai Univ, Fac Med, Chiang Mai 50000, Thailand.
[Uribe Tirado, Liliana Maria; Bombi, Anna Silvia; Di Giunta, Laura; Pastorelli, Concetta] Univ Roma La Sapienza, Dept Psychol, I-00118 Rome, Italy.
[Uribe Tirado, Liliana Maria] Univ San Buenaventura, Medellin 050001, Colombia.
[Zelli, Arnaldo] Univ Rome Foro Italico, I-00121 Rome, Italy.
[Pena Alampay, Liane] Ateneo Manila Univ, Dept Psychol, Quezon City 1000, Metro Manila Na, Philippines.
[Al-Hassan, Suha M.] Hashemite Univ, Dept Special Educ, Hashemite 13133, Jordan.
[Bacchini, Dario] Univ Naples 2, Fac Psychol, I-80121 Naples, NA, Italy.
[Bornstein, Marc H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20810 USA.
[Chang, Lei] Chinese Univ Hong Kong, Dept Psychol, Hong Kong, Hong Kong, Peoples R China.
[Deater-Deckard, Kirby] Virginia Polytech Inst & State Univ, Dept Psychol, Blacksburg, VA 24060 USA.
[Oburu, Paul] Maseno Univ, Maseno 40105, Kenya.
RP Dodge, KA (reprint author), Duke Univ, Ctr Child & Family Policy, Durham, NC 27708 USA.
EM dodge@duke.edu
RI ZELLI, ARNALDO/N-2333-2015;
OI ZELLI, ARNALDO/0000-0003-4020-8159; Bacchini, Dario/0000-0001-6140-9377
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD) [RO1-HD054805]; Fogarty International Center
[RO3-TW008141]; National Institute on Drug Abuse [K01DA024116, 2K05
DA015226]; National Institutes of Health/NICHD
FX This work was funded by Eunice Kennedy Shriver National Institute of
Child Health and Human Development (NICHD) Grant RO1-HD054805 and
Fogarty International Center Grant RO3-TW008141. P.S.M. was supported by
National Institute on Drug Abuse Grant K01DA024116. K.A.D. was supported
by National Institute on Drug Abuse Senior Scientist Award 2K05
DA015226. This work was also supported by the Intramural Research
Program of the National Institutes of Health/NICHD.
NR 25
TC 5
Z9 5
U1 1
U2 17
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 28
PY 2015
VL 112
IS 30
BP 9310
EP 9315
DI 10.1073/pnas.1418572112
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN7ZW
UT WOS:000358656500058
PM 26170281
ER
PT J
AU McGlinchey, RP
Lee, JC
AF McGlinchey, Ryan P.
Lee, Jennifer C.
TI Cysteine cathepsins are essential in lysosomal degradation of
alpha-synuclein
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE amyloid; Parkinson's disease; mass spectrometry; lysosomes;
protein-lipid interactions
ID PARKINSONS-DISEASE; IN-VIVO; NEURODEGENERATIVE DISEASES;
ALZHEIMERS-DISEASE; FIBRIL FORMATION; MOUSE-BRAIN; CYSTATIN-C;
AGGREGATION; PROTEIN; SYSTEM
AB A cellular feature of Parkinson's disease is cytosolic accumulation and amyloid formation of a-synuclein (alpha-syn), implicating a misregulation or impairment of protein degradation pathways involving the proteasome and lysosome. Within lysosomes, cathepsin D (CtsD), an aspartyl protease, is suggested to be the main protease for alpha-syn clearance; however, the protease alone only generates amyloidogenic C terminal-truncated species (e. g., 1-94, 5-94), implying that other proteases and/or environmental factors are needed to facilitate degradation and to avoid alpha-syn aggregation in vivo. Using liquid chromatography-mass spectrometry, to our knowledge, we report the first peptide cleavage map of the lysosomal degradation process of alpha-syn. Studies of purified mouse brain and liver lysosomal extracts and individual human cathepsins demonstrate a direct involvement of cysteine cathepsin B (CtsB) and L (CtsL). Both CtsB and CtsL cleave alpha-syn within its amyloid region and circumvent fibril formation. For CtsD, only in the presence of anionic phospholipids can this protease cleave throughout the alpha-syn sequence, suggesting that phospholipids are crucial for its activity. Taken together, an interplay exists between alpha-syn conformation and cathepsin activity with CtsL as the most efficient under the conditions examined. Notably, we discovered that CtsL efficiently degrades alpha-syn amyloid fibrils, which by definition are resistant to broad spectrum proteases. This work implicates CtsB and CtsL as essential in alpha-syn lysosomal degradation, establishing groundwork to explore mechanisms to enhance their cellular activity and levels as a potential strategy for clearance of alpha-syn.
C1 [McGlinchey, Ryan P.; Lee, Jennifer C.] NHLBI, Lab Mol Biophys, Biochem & Biophys Ctr, Bethesda, MD 20892 USA.
RP Lee, JC (reprint author), NHLBI, Lab Mol Biophys, Biochem & Biophys Ctr, Bldg 10, Bethesda, MD 20892 USA.
EM leej4@mail.nih.gov
RI Lee, Jennifer/E-9658-2015
OI Lee, Jennifer/0000-0003-0506-8349
FU National Institutes of Health, NHLBI
FX We thank Dr. Alan Remaley [National Institutes of Health, National
Heart, Lung, and Blood Institute (NHLBI)] for providing isolated liver
lysosomes and mouse brains. This work was supported by the Intramural
Research Program at the National Institutes of Health, NHLBI. We
acknowledge the NHLBI Biochemistry and EM Cores for use of the liquid
chromatography-mass spectrometry equipment and electron microscope,
respectively.
NR 50
TC 16
Z9 16
U1 5
U2 29
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 JUL 28
PY 2015
VL 112
IS 30
BP 9322
EP 9327
DI 10.1073/pnas.1500937112
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN7ZW
UT WOS:000358656500060
PM 26170293
ER
PT J
AU Holmes, JB
Akman, G
Wood, SR
Sakhuja, K
Cerritelli, SM
Moss, C
Bowmaker, MR
Jacobs, HT
Crouch, RJ
Holt, IJ
AF Holmes, J. Bradley
Akman, Gokhan
Wood, Stuart R.
Sakhuja, Kiran
Cerritelli, Susana M.
Moss, Chloe
Bowmaker, Mark R.
Jacobs, Howard T.
Crouch, Robert J.
Holt, Ian J.
TI Primer retention owing to the absence of RNase H1 is catastrophic for
mitochondrial DNA replication
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE DNA replication; RNase H; mitochondrial DNA; replication priming; origin
of replication
ID STRAND SYNTHESIS; RIBONUCLEASE-H; LAGGING-STRAND; ORIGIN; MOUSE;
INITIATION; TRANSCRIPTION; MECHANISM; SEQUENCE; MAINTENANCE
AB Encoding ribonuclease H1 (RNase H1) degrades RNA hybridized to DNA, and its function is essential for mitochondrial DNA maintenance in the developing mouse. Here we define the role of RNase H1 in mitochondrial DNA replication. Analysis of replicating mitochondrial DNA in embryonic fibroblasts lacking RNase H1 reveals retention of three primers in the major noncoding region (NCR) and one at the prominent lagging-strand initiation site termed Ori-L. Primer retention does not lead immediately to depletion, as the persistent RNA is fully incorporated in mitochondrial DNA. However, the retained primers present an obstacle to the mitochondrial DNA polymerase. in subsequent rounds of replication and lead to the catastrophic generation of a double-strand break at the origin when the resulting gapped molecules are copied. Hence, the essential role of RNase H1 in mitochondrial DNA replication is the removal of primers at the origin of replication.
C1 [Holmes, J. Bradley; Sakhuja, Kiran; Cerritelli, Susana M.; Crouch, Robert J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
[Holmes, J. Bradley; Wood, Stuart R.] MRC, Mitochondrial Biol Unit, Cambridge CB1 9SY, England.
[Akman, Gokhan; Moss, Chloe; Bowmaker, Mark R.; Holt, Ian J.] Natl Inst Med Res, MRC, London NW7 1AA, England.
[Jacobs, Howard T.] Univ Tampere, BioMediTech, FI-33014 Tampere, Finland.
[Jacobs, Howard T.] Univ Tampere, Tampere Univ Hosp, FI-33014 Tampere, Finland.
[Jacobs, Howard T.] Univ Helsinki, Res Program Mol Neurol, FI-00014 Helsinki, Finland.
RP Crouch, RJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
EM robert.crouch@nih.gov; ian.holt@crick.ac.uk
FU Medical Research Council; NIH [GM31819]; Eunice Kennedy Shriver National
Institute of Child Health and Human Development; Academy of Finland;
Juselius Foundation; Tampere University Hospital Medical Research Fund
FX J.B.H. was an National Institutes of Health (NIH) CamGrad Scholar
(2006-2010). This study was funded by the Medical Research Council, NIH
Grant GM31819, the Intramural Research Program of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development,
Academy of Finland, Juselius Foundation, and Tampere University Hospital
Medical Research Fund.
NR 36
TC 9
Z9 9
U1 0
U2 3
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 28
PY 2015
VL 112
IS 30
BP 9334
EP 9339
DI 10.1073/pnas.1503653112
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN7ZW
UT WOS:000358656500062
PM 26162680
ER
PT J
AU Wan, CK
Andraski, AB
Spolski, R
Li, P
Kazemian, M
Oh, J
Samsel, L
Swanson, PA
McGavern, DB
Sampaio, EP
Freeman, AF
Milner, JD
Holland, SM
Leonard, WJ
AF Wan, Chi-Keung
Andraski, Allison B.
Spolski, Rosanne
Li, Peng
Kazemian, Majid
Oh, Jangsuk
Samsel, Leigh
Swanson, Phillip A., II
McGavern, Dorian B.
Sampaio, Elizabeth P.
Freeman, Alexandra F.
Milner, Joshua D.
Holland, Steven M.
Leonard, Warren J.
TI Opposing roles of STAT1 and STAT3 in IL-21 function in CD4(+) T cells
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE IL-21; T cells; STATs; IFN-gamma; AD-HIES
ID CHRONIC VIRAL-INFECTION; FOLLICULAR-HELPER-CELLS; HYPER-IGE SYNDROME;
TRANSCRIPTION FACTOR; INTERFERON-GAMMA; CUTTING EDGE; INTERLEUKIN-21;
DIFFERENTIATION; GENERATION; T-HELPER-1
AB IL-21 is a type I cytokine essential for immune cell differentiation and function. Although IL-21 can activate several STAT family transcription factors, previous studies focused mainly on the role of STAT3 in IL-21 signaling. Here, we investigated the role of STAT1 and show that STAT1 and STAT3 have at least partially opposing roles in IL-21 signaling in CD4(+) T cells. IL-21 induced STAT1 phosphorylation, and this was augmented in Stat3-deficient CD4(+) T cells. RNA-Seq analysis of CD4(+) T cells from Stat1- and Stat3-deficient mice revealed that both STAT1 and STAT3 are critical for IL-21-mediated gene regulation. Expression of some genes, including Tbx21 and Ifng, was differentially regulated by STAT1 and STAT3. Moreover, opposing actions of STAT1 and STAT3 on IFN-gamma expression in CD4(+) T cells were demonstrated in vivo during chronic lymphocytic choriomeningitis infection. Finally, IL-21-mediated induction of STAT1 phosphorylation, as well as IFNG and TBX21 expression, were higher in CD4(+) T cells from patients with autosomal dominant hyper-IgE syndrome, which is caused by STAT3 deficiency, as well as in cells from STAT1 gain-of-function patients. These data indicate an interplay between STAT1 and STAT3 in fine-tuning IL-21 actions.
C1 [Wan, Chi-Keung; Andraski, Allison B.; Spolski, Rosanne; Li, Peng; Kazemian, Majid; Oh, Jangsuk; Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Wan, Chi-Keung; Andraski, Allison B.; Spolski, Rosanne; Li, Peng; Kazemian, Majid; Oh, Jangsuk; Leonard, Warren J.] NHLBI, Ctr Immunol, NIH, Bethesda, MD 20892 USA.
[Samsel, Leigh] NHLBI, Flow Cytometry Core, NIH, Bethesda, MD 20892 USA.
[Swanson, Phillip A., II; McGavern, Dorian B.] NINDS, Viral Immunol & Intravital Imaging Sect, NIH, Bethesda, MD 20892 USA.
[Sampaio, Elizabeth P.; Freeman, Alexandra F.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Milner, Joshua D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM wjl@helix.nih.gov
OI Kazemian, Majid/0000-0001-7080-8820
FU Division of Intramural Research, National Heart, Lung, and Blood
Institute, National Institutes of Health; Division of Intramural
Research, National Institute of Neurological Disorders and Stroke,
National Institutes of Health; Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health
FX We thank Dr. Jian-Xin Lin (National Heart, Lung, and Blood Institute)
for critical comments. This work was supported by the Divisions of
Intramural Research, National Heart, Lung, and Blood Institute, National
Institute of Neurological Disorders and Stroke, and National Institute
of Allergy and Infectious Diseases, National Institutes of Health.
RNA-Seq and ChIP-Seq were performed in the National Heart, Lung, and
Blood Institute DNA Sequencing and Genomics Core.
NR 34
TC 13
Z9 14
U1 1
U2 5
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 28
PY 2015
VL 112
IS 30
BP 9394
EP 9399
DI 10.1073/pnas.1511711112
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN7ZW
UT WOS:000358656500072
PM 26170288
ER
PT J
AU Xiong, XL
Corti, D
Liu, JF
Pinna, D
Foglierini, M
Calder, LJ
Martin, SR
Lin, YP
Walker, PA
Collins, PJ
Monne, I
Suguitan, AL
Santos, C
Temperton, NJ
Subbarao, K
Lanzavecchia, A
Gamblin, SJ
Skehel, JJ
AF Xiong, Xiaoli
Corti, Davide
Liu, Junfeng
Pinna, Debora
Foglierini, Mathilde
Calder, Lesley J.
Martin, Stephen R.
Lin, Yi Pu
Walker, Philip A.
Collins, Patrick J.
Monne, Isabella
Suguitan, Amorsolo L., Jr.
Santos, Celia
Temperton, Nigel J.
Subbarao, Kanta
Lanzavecchia, Antonio
Gamblin, Steven J.
Skehel, John J.
TI Structures of complexes formed by H5 influenza hemagglutinin with a
potent broadly neutralizing human monoclonal antibody
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE influenza virus; neutralizing antibody; H5N1
ID VIRUS HEMAGGLUTININ; RECEPTOR-BINDING; CELLS; MECHANISM; SUBTYPE;
EPITOPE; PLASMA; HA
AB H5N1 avian influenza viruses remain a threat to public health mainly because they can cause severe infections in humans. These viruses are widespread in birds, and they vary in antigenicity forming three major clades and numerous antigenic variants. The most important features of the human monoclonal antibody FLD194 studied here are its broad specificity for all major clades of H5 influenza HAs, its high affinity, and its ability to block virus infection, in vitro and in vivo. As a consequence, this antibody may be suitable for anti-H5 therapy and as a component of stockpiles, together with other antiviral agents, for health authorities to use if an appropriate vaccine was not available. Our mutation and structural analyses indicate that the antibody recognizes a relatively conserved site near the membrane distal tip of HA, near to, but distinct from, the receptor-binding site. Our analyses also suggest that the mechanism of infectivity neutralization involves prevention of receptor recognition as a result of steric hindrance by the Fc part of the antibody. Structural analyses by EM indicate that three Fab fragments are bound to each HA trimer. The structure revealed by X-ray crystallography is of an HA monomer bound by one Fab. The monomer has some similarities to HA in the fusion pH conformation, and the monomer's formation, which results from the presence of isopropanol in the crystallization solvent, contributes to considerations of the process of change in conformation required formembrane fusion.
C1 [Xiong, Xiaoli; Calder, Lesley J.; Lin, Yi Pu; Collins, Patrick J.; Gamblin, Steven J.; Skehel, John J.] Francis Crick Inst, Mill Hill Lab, London NW7 1AA, England.
[Corti, Davide; Pinna, Debora; Foglierini, Mathilde; Lanzavecchia, Antonio] Inst Res Biomed, CH-6500 Bellinzona, Switzerland.
[Liu, Junfeng] China Agr Univ, Minist Agr Key Lab Plant Pathol, Beijing 100193, Peoples R China.
[Martin, Stephen R.; Walker, Philip A.] Francis Crick Inst, Mill Hill Lab, Struct Biol Sci Technol Platform, London NW7, England.
[Monne, Isabella] Ist Zooprofilatt Sperimentale Venezie, I-35020 Padua, Italy.
[Suguitan, Amorsolo L., Jr.; Santos, Celia; Subbarao, Kanta] NIAID, Lab Infect Dis, NIH, Bethesda, MD 20892 USA.
[Temperton, Nigel J.] Univ Kent, Viral Pseudotype Unit, Chatham ME4 4TB, Kent, England.
RP Skehel, JJ (reprint author), Francis Crick Inst, Mill Hill Lab, London NW7 1AA, England.
EM John.Skehel@crick.ac.uk
OI Gamblin, Steven/0000-0001-5331-639X; Temperton,
Nigel/0000-0002-7978-3815
FU Medical Research Council [U117584222, U117512723, U117570592]; NoFlu
project, Fondazione Cariplo Vaccine Program [2009-3594]; Division of
Intramural Research, National Institute of Allergy and Infectious
Diseases, National Institutes of Health
FX We thank the staff at the Diamond Light Source Synchrotron for
assistance and beamline access under Diamond Light Source Proposal 7707.
We thank Cameron Simmons (Oxford University Clinical Research Unit and
the Hospital for Tropical Diseases) for collection of clinical samples
and Silvia Maniero [Istituto Zooprofilattico Sperimentale delle Venezie
(IZSVe)], Prof. Hussein A. Hussein (Cairo University), and Dr. Abdo
Arafa (National Laboratory for Veterinary Quality Control on Poultry
Production) for excellent technical assistance. This work was funded by
the Medical Research Council through Programmes U117584222, U117512723,
and U117570592. IZSVe activities were financially supported by the NoFlu
project, Fondazione Cariplo Vaccine Program Grant 2009-3594. This
research was supported, in part, by the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 27
TC 4
Z9 4
U1 3
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 JUL 28
PY 2015
VL 112
IS 30
BP 9430
EP 9435
DI 10.1073/pnas.1510816112
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN7ZW
UT WOS:000358656500078
PM 26170284
ER
PT J
AU Desai, PN
Zhang, XX
Wu, SL
Janoshazi, A
Bolimuntha, S
Putney, JW
Trebak, M
AF Desai, Pooja N.
Zhang, Xuexin
Wu, Shilan
Janoshazi, Agnes
Bolimuntha, Sunitha
Putney, James W.
Trebak, Mohamed
TI Multiple types of calcium channels arising from alternative translation
initiation of the Orai1 message
SO SCIENCE SIGNALING
LA English
DT Article
ID CA2+ ENTRY; PLASMA-MEMBRANE; ARC CHANNELS; HEK293 CELLS; STORE;
ACTIVATION; STIM1; POTENTIATION; LYMPHOCYTES; MECHANISM
AB In mammals exclusively, the pore-forming Ca2+ release-activated Ca2+ (CRAC) channel subunit Orai1 occurs in two forms because of alternative translation initiation. The longer, mammal-specific Orai1 alpha contains an additional 63 amino acids upstream of the conserved start site for Orai1 beta, which occurs at methionine 64 in Orai1 alpha. Orai1 participates in the generation of three distinct Ca2+ currents, including two store-operated currents: I-crac, which involves activation of Orai1 channels by the Ca2+-sensing protein STIM1 (stromal interaction molecule 1), and I-soc, which involves an interaction among Orai1, the transient receptor potential (TRP) family member TRPC1 (TRP canonical 1), and STIM1. Orai1 is also a pore-forming subunit of an arachidonic acid (or leukotriene C-4)-regulated current I-arc that involves interactions among Orai1, Orai3, and STIM1. We evaluated the roles of the two Orai1 forms in the Ca2+ currents I-crac, I-soc, and I-arc. We found that Orai1 alpha and Orai1 beta were largely interchangeable for I-crac and I-soc, although Orai1 alpha exhibited stronger inhibition by Ca2+. Only the mammalian-specific Orai1 alpha functioned in the arachidonic acid-regulated current I-arc. Thus, alternative translation initiation of the Orai1 message produces at least three types of Ca2+ channels with distinct signaling and regulatory properties.
C1 [Desai, Pooja N.; Wu, Shilan; Janoshazi, Agnes; Bolimuntha, Sunitha; Putney, James W.] NIEHS, Signal Transduct Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Zhang, Xuexin; Trebak, Mohamed] Penn State Univ, Dept Cellular & Mol Physiol, Coll Med, Hershey, PA 17033 USA.
RP Putney, JW (reprint author), NIEHS, Signal Transduct Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
EM putney@niehs.nih.gov; mtrebak@hmc.psu.edu
FU Intramural Research Program, NIH; NIH [R01HL097111, R01HL123364];
American Heart Association [14GRNT18880008]
FX Work described in this publication was supported in part by the
Intramural Research Program, NIH, and by grants R01HL097111 and
R01HL123364 from the NIH and American Heart Association grant
14GRNT18880008 to M.T.
NR 31
TC 15
Z9 15
U1 1
U2 8
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 JUL 28
PY 2015
VL 8
IS 387
AR ra74
DI 10.1126/scisignal.aaa8323
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CN7DK
UT WOS:000358594000001
PM 26221052
ER
PT J
AU Suinesiaputra, A
Bluemke, DA
Cowan, BR
Friedrich, MG
Kramer, CM
Kwong, R
Plein, S
Schulz-Menger, J
Westenberg, JJM
Young, AA
Nagel, E
AF Suinesiaputra, Avan
Bluemke, David A.
Cowan, Brett R.
Friedrich, Matthias G.
Kramer, Christopher M.
Kwong, Raymond
Plein, Sven
Schulz-Menger, Jeanette
Westenberg, Jos J. M.
Young, Alistair A.
Nagel, Eike
TI Quantification of LV function and mass by cardiovascular magnetic
resonance: multi-center variability and consensus contours
SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE
LA English
DT Article
DE Left ventricular function; Benchmarks; Reproducibility; Multi-center;
Left ventricular mass; Image analysis
ID LEFT-VENTRICULAR MASS; ECHOCARDIOGRAPHY; ATHEROSCLEROSIS;
REPRODUCIBILITY; SEGMENTATION; PERFORMANCE; ALGORITHM; HEART; SHAPE
AB Background: High reproducibility of LV mass and volume measurement from cine cardiovascular magnetic resonance (CMR) has been shown within single centers. However, the extent to which contours may vary from center to center, due to different training protocols, is unknown. We aimed to quantify sources of variation between many centers, and provide a multi-center consensus ground truth dataset for benchmarking automated processing tools and facilitating training for new readers in CMR analysis.
Methods: Seven independent expert readers, representing seven experienced CMR core laboratories, analyzed fifteen cine CMR data sets in accordance with their standard operating protocols and SCMR guidelines. Consensus contours were generated for each image according to a statistical optimization scheme that maximized contour placement agreement between readers.
Results: Reader-consensus agreement was better than inter-reader agreement (end-diastolic volume 14.7 ml vs 15.2-28.4 ml; end-systolic volume 13.2 ml vs 14.0-21.5 ml; LV mass 17.5 g vs 20.2-34.5 g; ejection fraction 4.2 % vs 4.6-7.5 %). Compared with consensus contours, readers were very consistent (small variability across cases within each reader), but bias varied between readers due to differences in contouring protocols at each center. Although larger contour differences were found at the apex and base, the main effect on volume was due to small but consistent differences in the position of the contours in all regions of the LV.
Conclusions: A multi-center consensus dataset was established for the purposes of benchmarking and training. Achieving consensus on contour drawing protocol between centers before analysis, or bias correction after analysis, is required when collating multi-center results.
C1 [Suinesiaputra, Avan; Cowan, Brett R.; Young, Alistair A.] Univ Auckland, Dept Anat Radiol, Auckland 1, New Zealand.
[Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, Bethesda, MD USA.
[Friedrich, Matthias G.] McGill Univ, Dept Med, Montreal, PQ, Canada.
[Friedrich, Matthias G.] McGill Univ, Dept Diagnost Radiol, Montreal, PQ, Canada.
[Kramer, Christopher M.] Univ Virginia, Charlottesville, VA USA.
[Kwong, Raymond] Harvard Univ, Sch Med, Boston, MA USA.
[Plein, Sven] Univ Leeds, Leeds, W Yorkshire, England.
[Westenberg, Jos J. M.] Leiden Univ, Med Ctr, Leiden, Netherlands.
[Schulz-Menger, Jeanette] Charite, D-13353 Berlin, Germany.
[Schulz-Menger, Jeanette] HELIOS Klinikum Berlin Buch, Berlin, Germany.
[Nagel, Eike] Univ Hosp Frankfurt Main, DZHK Ctr Cardiovasc Imaging, Inst Expt & Translat Cardiovasc Imaging, Frankfurt, Germany.
RP Young, AA (reprint author), Univ Auckland, Dept Anat Radiol, Auckland 1, New Zealand.
EM a.young@auckland.ac.nz
OI Bluemke, David/0000-0002-8323-8086
FU National Heart, Lung, and Blood Institute [R01HL087773, R01HL121754]
FX This project was supported by Awards R01HL087773 and R01HL121754 from
the National Heart, Lung, and Blood Institute. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Heart, Lung, and Blood Institute or the
National Institutes of Health.
NR 19
TC 6
Z9 6
U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1097-6647
EI 1532-429X
J9 J CARDIOVASC MAGN R
JI J. Cardiov. Magn. Reson.
PD JUL 28
PY 2015
VL 17
AR 63
DI 10.1186/s12968-015-0170-9
PG 8
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA CN5NE
UT WOS:000358475200001
PM 26215273
ER
PT J
AU Herz, J
Johnson, KR
McGavern, DB
AF Herz, Jasmin
Johnson, Kory R.
McGavern, Dorian B.
TI Therapeutic antiviral T cells noncytopathically clear persistently
infected microglia after conversion into antigen-presenting cells
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID CENTRAL-NERVOUS-SYSTEM; LYMPHOCYTIC CHORIOMENINGITIS VIRUS; EMERGING
VIRAL-INFECTIONS; BRAIN DENDRITIC CELLS; IN-VIVO; INTERFERON-GAMMA;
TRANSGENIC MICE; IMMUNOLOGICAL TOLERANCE; ADOPTIVE IMMUNOTHERAPY;
INFLAMMATORY MONOCYTES
AB Several viruses can infect the mammalian nervous system and induce neurological dysfunction. Adoptive immunotherapy is an approach that involves administration of antiviral T cells and has shown promise in clinical studies for the treatment of peripheral virus infections in humans such as cytomegalovirus (CMV), Epstein-Barr virus (EBV), and adenovirus, among others. In contrast, clearance of neurotropic infections is particularly challenging because the central nervous system (CNS) is relatively intolerant of immunopathological reactions. Therefore, it is essential to develop and mechanistically understand therapies that noncyto-pathically eradicate pathogens from the CNS. Here, we used mice persistently infected from birth with lymphocytic choriomeningitis virus (LCMV) to demonstrate that therapeutic anti-viral T cells can completely purge the persistently infected brain without causing blood-brain barrier breakdown or tissue damage. Mechanistically, this is accomplished through a tailored release of chemoattractants that recruit antiviral T cells, but few pathogenic innate immune cells such as neutrophils and inflammatory monocytes. Upon arrival, T cells enlisted the support of nearly all brain-resident myeloid cells (microglia) by inducing proliferation and converting them into CD11c(+) antigen-presenting cells (APCs). Two-photon imaging experiments revealed that antiviral CD8(+) and CD4(+) T cells interacted directly with CD11c(+) microglia and induced STAT1 signaling but did not initiate programmed cell death. We propose that noncytopathic CNS viral clearance can be achieved by therapeutic antiviral T cells reliant on restricted chemoattractant production and interactions with apoptosis-resistant microglia.
C1 [Herz, Jasmin; Johnson, Kory R.; McGavern, Dorian B.] NINDS, NIH, Bethesda, MD 20892 USA.
RP McGavern, DB (reprint author), NINDS, NIH, Bethesda, MD 20892 USA.
EM mcgavernd@mail.nih.gov
FU National Institutes of Health Intramural Research Program; German
Research Foundation (DFG) [HE-6068/1-1]
FX This work was supported by the National Institutes of Health Intramural
Research Program (to D.B. McGavern) and fellowship HE-6068/1-1 from the
German Research Foundation (DFG; to J. Herz).
NR 78
TC 14
Z9 14
U1 1
U2 3
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA
SN 0022-1007
EI 1540-9538
J9 J EXP MED
JI J. Exp. Med.
PD JUL 27
PY 2015
VL 212
IS 8
BP 1153
EP 1169
DI 10.1084/jem.20142047
PG 17
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA CQ1SO
UT WOS:000360379400002
PM 26122661
ER
PT J
AU Rissone, A
Weinacht, KG
la Marca, G
Bishop, K
Giocaliere, E
Jagadeesh, J
Felgentreff, K
Dobbs, K
Al-Herz, W
Jones, M
Chandrasekharappa, S
Kirby, M
Wincovitch, S
Simon, KL
Itan, Y
DeVine, A
Schlaeger, T
Schambach, A
Sood, R
Notarangelo, LD
Candotti, F
AF Rissone, Alberto
Weinacht, Katja Gabriele
la Marca, Giancarlo
Bishop, Kevin
Giocaliere, Elisa
Jagadeesh, Jayashree
Felgentreff, Kerstin
Dobbs, Kerry
Al-Herz, Waleed
Jones, Marypat
Chandrasekharappa, Settara
Kirby, Martha
Wincovitch, Stephen
Simon, Karen Lyn
Itan, Yuval
DeVine, Alex
Schlaeger, Thorsten
Schambach, Axel
Sood, Raman
Notarangelo, Luigi D.
Candotti, Fabio
TI Reticular dysgenesis-associated AK2 protects hematopoietic stem and
progenitor cell development from oxidative stress
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID ADENYLATE KINASE 2; MYELODYSPLASTIC SYNDROME; TRANSGENIC ZEBRAFISH;
VASCULAR DEVELOPMENT; KNOCKOUT HEART; OMENN SYNDROME; GENE; GROWTH;
TRANSPLANTATION; EXPRESSION
AB Adenylate kinases (AKs) are phosphotransferases that regulate the cellular adenine nucleotide composition and play a critical role in the energy homeostasis of all tissues. The AK2 isoenzyme is expressed in the mitochondrial intermembrane space and is mutated in reticular dysgenesis (RD), a rare form of severe combined immunodeficiency (SCID) in humans. RD is characterized by a maturation arrest in the myeloid and lymphoid lineages, leading to early onset, recurrent, and overwhelming infections. To gain insight into the pathophysiology of RD, we studied the effects of AK2 deficiency using the zebrafish model and induced pluripotent stem cells (iPSCs) derived from fibroblasts of an RD patient. In zebrafish, Ak2 deficiency affected hematopoietic stem and progenitor cell (HSPC) development with increased oxidative stress and apoptosis. AK2-deficient iPSCs recapitulated the characteristic myeloid maturation arrest at the promyelocyte stage and demonstrated an increased AMP/ADP ratio, indicative of an energy-depleted adenine nucleotide profile. Antioxidant treatment rescued the hematopoietic phenotypes in vivo in ak2 mutant zebrafish and restored differentiation of AK2-deficient iPSCs into mature granulocytes. Our results link hematopoietic cell fate in AK2 deficiency to cellular energy depletion and increased oxidative stress. This points to the potential use of antioxidants as a supportive therapeutic modality for patients with RD.
C1 [Rissone, Alberto; Jagadeesh, Jayashree; Simon, Karen Lyn; Candotti, Fabio] NHGRI, Disorders Immun Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
[Bishop, Kevin; Sood, Raman] NHGRI, Zebrafish Core, NIH, Bethesda, MD 20892 USA.
[Sood, Raman] NHGRI, Oncogenesis & Dev Sect, Translat & Funct Genom Branch, NIH, Bethesda, MD 20892 USA.
[Jones, Marypat; Chandrasekharappa, Settara] NHGRI, Genom Core, Canc Genet & Comparat Genom Branch, NIH, Bethesda, MD 20892 USA.
[Kirby, Martha] NHGRI, Div Intramural Res Flow Cytometry Core, NIH, Bethesda, MD 20892 USA.
[Wincovitch, Stephen] NHGRI, Cytogenet & Microscopy Core, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
[Weinacht, Katja Gabriele; DeVine, Alex; Schlaeger, Thorsten; Schambach, Axel] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
[Felgentreff, Kerstin; Dobbs, Kerry; Notarangelo, Luigi D.] Boston Childrens Hosp, Div Immunol, Boston, MA 02115 USA.
[Weinacht, Katja Gabriele] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[la Marca, Giancarlo] Univ Florence, Dept Neurosci Psychol Pharmacol & Child Hlth, I-51039 Florence, Italy.
[la Marca, Giancarlo; Giocaliere, Elisa] Meyer Childrens Univ Hosp, I-50141 Florence, Italy.
[Al-Herz, Waleed] Kuwait Univ, Dept Pediat, Fac Med, Kuwait 13110, Kuwait.
[Al-Herz, Waleed] Al Sabah Hosp, Dept Pediat, Allergy & Clin Immunol Unit, Kuwait 70459, Kuwait.
[Itan, Yuval] Rockefeller Univ, Rockefeller Branch, St Giles Lab Human Genet Infect Dis, New York, NY 10065 USA.
[Schambach, Axel] Hannover Med Sch, Inst Expt Hematol, D-30625 Hannover, Germany.
[Notarangelo, Luigi D.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
[Candotti, Fabio] Univ Lausanne Hosp, Div Immunol & Allergy, CH-1011 Lausanne, Switzerland.
RP Candotti, F (reprint author), NHGRI, Disorders Immun Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
EM Luigi.Notarangelo@childrens.harvard.edu; Fabio.Candotti@chuv.ch
RI Notarangelo, Luigi/F-9718-2016;
OI Notarangelo, Luigi/0000-0002-8335-0262; la marca,
giancarlo/0000-0003-3319-7260
FU National Institute of Allergy and Infectious Diseases (NIAID)
[5R01AI100887]; Manton Foundation; Intramural Research Program of the
National Human Genome Research Institute; UNIL-CHUV grant [CGRB 29583];
EU FP7 program Cellpid and Cluster of Excellence REBIRTH (DFG); Kuwait
Foundation for Advancement of Science [2010-1302-05]; Amy Potter
Fellowship; Charles King Trust; Primary Immune Deficiency Treatment
Consortium; NIAID [1U54AI082973]
FX This work was supported in part by grant 5R01AI100887 from the National
Institute of Allergy and Infectious Diseases (NIAID) and by the Manton
Foundation (to L.D. Notarangelo), by funding from the Intramural
Research Program of the National Human Genome Research Institute (to F.
Candotti, R. Sood, and S. Chandrasekharappa), by UNIL-CHUV grant CGRB
29583 (to F. Candotti), by EU FP7 program Cellpid and Cluster of
Excellence REBIRTH (DFG; to A. Schambach), and by the Kuwait Foundation
for Advancement of Science (2010-1302-05; to W. Al-Herz). K.G.
Weinacht's work was supported by the Amy Potter Fellowship, the Charles
King Trust, and the Primary Immune Deficiency Treatment Consortium and
funded by grant 1U54AI082973 from NIAID.
NR 61
TC 4
Z9 4
U1 1
U2 3
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA
SN 0022-1007
EI 1540-9538
J9 J EXP MED
JI J. Exp. Med.
PD JUL 27
PY 2015
VL 212
IS 8
BP 1185
EP 1202
DI 10.1084/jem.20141286
PG 18
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA CQ1SO
UT WOS:000360379400004
PM 26150473
ER
PT J
AU Greenblatt, MB
Park, KH
Oh, H
Kim, JM
Shin, DY
Lee, JM
Lee, JW
Singh, A
Lee, KY
Hu, D
Xiao, CC
Charles, JF
Penninger, JM
Lotinun, S
Baron, R
Ghosh, S
Shim, JH
AF Greenblatt, Matthew B.
Park, Kwang Hwan
Oh, Hwanhee
Kim, Jung-Min
Shin, Dong Yeon
Lee, Jae Myun
Lee, Jin Woo
Singh, Anju
Lee, Ki-young
Hu, Dorothy
Xiao, Changchun
Charles, Julia F.
Penninger, Josef M.
Lotinun, Sutada
Baron, Roland
Ghosh, Sankar
Shim, Jae-Hyuck
TI CHMP5 controls bone turnover rates by dampening NF-kappa B activity in
osteoclasts
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID VALOSIN-CONTAINING PROTEIN; JUVENILE PAGETS-DISEASE; GENOME-WIDE
ASSOCIATION; MESENCHYMAL STEM-CELLS; C-SRC; OSTEOBLAST DIFFERENTIATION;
GENE-EXPRESSION; ESCRT-III; RESORPTION; COMPLEX
AB Physiological bone remodeling requires that bone formation by osteoblasts be tightly coupled to bone resorption by osteoclasts. However, relatively little is understood about how this coupling is regulated. Here, we demonstrate that modulation of NF-kappa B signaling in osteoclasts via a novel activity of charged multivesicular body protein 5 (CHMP5) is a key determinant of systemic rates of bone turnover. A conditional deletion of CHMP5 in osteoclasts leads to increased bone resorption by osteoclasts coupled with exuberant bone formation by osteoblasts, resembling an early onset, polyostotic form of human Paget's disease of bone (PDB). These phenotypes are reversed by haploinsufficiency for Rank, as well as by antiresorptive treatments, including alendronate, zolendronate, and OPG-Fc. Accordingly, CHMP5-deficient osteoclasts display increased RANKL-induced NF-kappa B activation and osteoclast differentiation. Biochemical analysis demonstrated that CHMP5 cooperates with the PDB genetic risk factor valosin-containing protein (VCP/p97) to stabilize the inhibitor of NF-kappa B alpha (I kappa B alpha), down-regulating ubiquitination of I kappa B alpha via the deubiquitinating enzyme USP15. Thus, CHMP5 tunes NF-kappa B signaling downstream of RANK in osteoclasts to dampen osteoclast differentiation, osteoblast coupling and bone turnover rates, and disruption of CHMP5 activity results in a PDB-like skeletal disorder.
C1 [Greenblatt, Matthew B.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Greenblatt, Matthew B.] Weill Cornell Med Coll, Dept Med, New York, NY 10065 USA.
[Park, Kwang Hwan; Oh, Hwanhee; Kim, Jung-Min; Shin, Dong Yeon; Shim, Jae-Hyuck] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY 10065 USA.
[Park, Kwang Hwan; Lee, Jae Myun] Yonsei Univ, Coll Med, Brain Korea PLUS Project Med Sci 21, Dept Microbiol, Seoul 120752, South Korea.
[Park, Kwang Hwan; Lee, Jin Woo] Yonsei Univ, Coll Med, Dept Orthopaed Surg, Seoul 120752, South Korea.
[Singh, Anju] NIH, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA.
[Lee, Ki-young] Sungkyunkwan Univ, Sch Med, Dept Mol Cell Biol, Suwon 440746, South Korea.
[Lee, Ki-young] Sungkyunkwan Univ, Sch Med, Samsung Biomed Res Inst, Suwon 440746, South Korea.
[Hu, Dorothy] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
[Xiao, Changchun] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
[Charles, Julia F.] Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Dept Med, Boston, MA 02115 USA.
[Charles, Julia F.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Penninger, Josef M.] Austrian Acad Sci, Inst Mol Biotechnol, A-1030 Vienna, Austria.
[Lotinun, Sutada; Baron, Roland] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA.
[Lotinun, Sutada] Chulalongkorn Univ, Dept Physiol, Bangkok 10330, Thailand.
[Lotinun, Sutada] Chulalongkorn Univ, STAR Craniofacial & Skeletal Disorders, Fac Dent, Bangkok 10330, Thailand.
[Ghosh, Sankar] Columbia Univ, Coll Phys & Surg, Dept Microbiol & Immunol, New York, NY 10032 USA.
RP Shim, JH (reprint author), Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY 10065 USA.
EM jas2060@med.cornell.edu
RI Penninger, Josef/I-6860-2013
OI Penninger, Josef/0000-0002-8194-3777
FU National Institute of Arthritis and Musculoskeletal and Skin
Diseases/National Institutes of Health [1 R01 AR068983-01]; Advanced
European Research Council grant; Era of Hope/Department of Defense
FX This work was supported by a grant from the National Institute of
Arthritis and Musculoskeletal and Skin Diseases/National Institutes of
Health (J.-H. Shim; 1 R01 AR068983-01). J.M. Penninger was supported by
an Advanced European Research Council grant and an Innovator Award from
the Era of Hope/Department of Defense.
NR 58
TC 3
Z9 3
U1 2
U2 6
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA
SN 0022-1007
EI 1540-9538
J9 J EXP MED
JI J. Exp. Med.
PD JUL 27
PY 2015
VL 212
IS 8
BP 1283
EP 1301
DI 10.1084/jem.20150407
PG 19
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA CQ1SO
UT WOS:000360379400010
PM 26195726
ER
PT J
AU Greiff, S
Wustenberg, S
Goetz, T
Vainikainen, MP
Hautamaki, J
Bornstein, MH
AF Greiff, Samuel
Wuestenberg, Sascha
Goetz, Thomas
Vainikainen, Mari-Pauliina
Hautamaeki, Jarkko
Bornstein, March H.
TI A longitudinal study of higher-order thinking skills: working memory and
fluid reasoning in childhood enhance complex problem solving in
adolescence
SO FRONTIERS IN PSYCHOLOGY
LA English
DT Article
DE cognitive development; complex problem solving; problem solving; working
memory; fluid reasoning
ID DEVELOPMENTAL CASCADE; COGNITIVE-DEVELOPMENT; INTELLIGENCE; IQ;
PERFORMANCE; ABILITIES; CONSTRUCT; CAPACITY; VALIDITY; INFANCY
AB Scientists have studied the development of the human mind for decades and have accumulated an impressive number of empirical studies that have provided ample support for the notion that early cognitive performance during infancy and childhood is an important predictor of later cognitive performance during adulthood. As children move from childhood into adolescence, their mental development increasingly involves higher-order cognitive skills that are crucial for successful planning, decision-making, and problem solving skills. However, few studies have employed higher-order thinking skills such as complex problem solving (CPS) as developmental outcomes in adolescents. To fill this gap, we tested a longitudinal developmental model in a sample of 2,021 Finnish sixth grade students (M = 12.41 years, SD = 0.52; 1,041 female, 978 male, 2 missing sex). We assessed working memory (WM) and fluid reasoning (FR) at age 12 as predictors of two CPS dimensions: knowledge acquisition and knowledge application. We further assessed students' CPS performance 3 years later as a developmental outcome (N = 1696; M = 15.22 years, SD = 0.43; 867 female, 829 male). Missing data partly occurred due to dropout and technical problems during the first days of testing and varied across indicators and time with a mean of 27.2%. Results revealed that FR was a strong predictor of both CPS dimensions, whereas WM exhibited only a small influence on one of the two CPS dimensions. These results provide strong support for the view that CPS involves FR and, to a lesser extent, WM in childhood and from there evolves into an increasingly complex structure of higher-order cognitive skills in adolescence.
C1 [Greiff, Samuel; Wuestenberg, Sascha] Univ Luxembourg, Educ Culture Cognit & Soc Unit, Luxembourg, Luxembourg.
[Goetz, Thomas] Univ Konstanz, Constance, Germany.
[Goetz, Thomas] Thurgau Univ Teacher Educ, Kreuzlingen, Switzerland.
[Vainikainen, Mari-Pauliina; Hautamaeki, Jarkko] Univ Helsinki, Helsinki, Finland.
[Bornstein, March H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Greiff, S (reprint author), Univ Luxembourg, Educ Culture Cognit & Soc Unit, 11 Porte Sci,4366 Esch, Luxembourg, Luxembourg.
EM samuel.greiff@uni.lu
FU Fonds National de la Recherche Luxembourg (ATTRACT "ASKI21"); Intramural
Research Program of the NIH, NICHD
FX This research was funded by a grant from the Fonds National de la
Recherche Luxembourg (ATTRACT "ASKI21") and by the Intramural Research
Program of the NIH, NICHD. We are grateful to the TBA group at DIPF
(http://tba.dipf.de) for providing the authoring tool CBA Item Builder
and technical support.
NR 51
TC 0
Z9 0
U1 7
U2 36
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1664-1078
J9 FRONT PSYCHOL
JI Front. Psychol.
PD JUL 27
PY 2015
VL 6
AR 1060
DI 10.3389/fpsyg.2015.01060
PG 9
WC Psychology, Multidisciplinary
SC Psychology
GA CP3AG
UT WOS:000359748600001
PM 26283992
ER
PT J
AU Gruschus, JM
AF Gruschus, James M.
TI Did alpha-Synuclein and Glucocerebrosidase Coevolve? Implications for
Parkinson's Disease
SO PLOS ONE
LA English
DT Article
ID PROTEIN-PROTEIN INTERACTION; ACID-BETA-GLUCOSIDASE; GAUCHER-DISEASE;
CORRELATED MUTATIONS; SAPOSIN C; IN-VIVO; X-RAY; COEVOLUTION; FAMILIES;
INFORMATION
AB Mutations in the GBA1 gene are associated with increased risk of Parkinson's disease, and the protein produced by the gene, glucocerebrosidase, interacts with alpha-synuclein, the protein at the center of the disease etiology. One possibility is that the mutations disrupt a beneficial interaction between the proteins, and a beneficial interaction would imply that the proteins have coevolved. To explore this possibility, a correlated mutation analysis has been performed for all 72 vertebrate species where complete sequences of alpha-synuclein and glucocerebrosidase are known. The most highly correlated pair of residue variations is alpha-synuclein A53T and glucocerebrosidase G115E. Intriguingly, the A53T mutation is a Parkinson's disease risk factor in humans, suggesting the pathology associated with this mutation and interaction with glucocerebrosidase might be connected. Correlations with beta-synuclein are also evaluated. To assess the impact of lowered species number on accuracy, intra and inter-chain correlations are also calculated for hemoglobin, using mutual information Z-value and direct coupling analyses.
C1 NHLBI, Lab Struct Biophys, NIH, Bethesda, MD 20892 USA.
RP Gruschus, JM (reprint author), NHLBI, Lab Struct Biophys, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM gruschuj@helix.nih.gov
FU Intramural Research Program at the National Institutes of Health,
National Heart, Lung, and Blood Institute (NHLBI)
FX This work was supported by the Intramural Research Program at the
National Institutes of Health, National Heart, Lung, and Blood Institute
(NHLBI).
NR 70
TC 2
Z9 2
U1 2
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 JUL 27
PY 2015
VL 10
IS 7
AR e0133863
DI 10.1371/journal.pone.0133863
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN7DN
UT WOS:000358594300036
PM 26214314
ER
PT J
AU Madeddu, S
Woods, TA
Mukherjee, P
Sturdevant, D
Butchi, NB
Peterson, KE
AF Madeddu, Silvia
Woods, Tyson A.
Mukherjee, Piyali
Sturdevant, Dan
Butchi, Niranjan B.
Peterson, Karin E.
TI Identification of Glial Activation Markers by Comparison of
Transcriptome Changes between Astrocytes and Microglia following Innate
Immune Stimulation
SO PLOS ONE
LA English
DT Article
ID TOLL-LIKE RECEPTORS; ALZHEIMER-DISEASE; DENDRITIC CELLS; NERVOUS-SYSTEM;
UP-REGULATION; EXPRESSION; VIRUS; CYTOKINES; TLR7; INTERFERON
AB The activation of astrocytes and microglia is often associated with diseases of the central nervous system (CNS). Understanding how activation alters the transcriptome of these cells may offer valuable insight regarding how activation of these cells mediate neurological damage. Furthermore, identifying common and unique pathways of gene expression during activation may provide new insight into the distinct roles these cells have in the CNS during infection and inflammation. Since recent studies indicate that TLR7 recognizes not only viral RNA but also microRNAs that are released by damaged neurons and elevated during neurological diseases, we first examined the response of glial cells to TLR7 stimulation using microarray analysis. Microglia were found to generate a much stronger response to TLR7 activation than astrocytes, both in the number of genes induced as well as fold induction. Although the primary pathways induced by both cell types were directly linked to immune responses, microglia also induced pathways associated with cellular proliferation, while astrocytes did not. Targeted analysis of a subset of the upregulated genes identified unique mRNA, including Ifi202b which was only upregulated by microglia and was found to be induced during both retroviral and bunyavirus infections in the CNS. In addition, other genes including Birc3 and Gpr84 as well as two expressed sequences AW112010 and BC023105 were found to be induced in both microglia and astrocytes and were upregulated in the CNS following virus infection. Thus, expression of these genes may a useful measurement of glial activation during insult or injury to the CNS.
C1 [Madeddu, Silvia; Woods, Tyson A.; Mukherjee, Piyali; Butchi, Niranjan B.; Peterson, Karin E.] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
[Sturdevant, Dan] NIAID, Res Technol Branch, RML, NIH, Hamilton, MT USA.
RP Peterson, KE (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
EM petersonka@niaid.nih.gov
RI Peterson, Karin/D-1492-2016
OI Peterson, Karin/0000-0003-4177-7249
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases (NIAID), National Institute of Health; Sardinia
Regional Government
FX This research was supported by the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases (NIAID), National
Institute of Health. The authors gratefully acknowledge the Sardinia
Regional Government for the financial support of Silvia Maddeddu through
her Ph.D. scholarship (P.O.R. Sardegna F.S.E Operational Programme of
the Autonomous Region of Sardinia, European Social Fund 2007-2013).
NR 52
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Z9 5
U1 2
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 JUL 27
PY 2015
VL 10
IS 7
AR e0127336
DI 10.1371/journal.pone.0127336
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN7DN
UT WOS:000358594300001
PM 26214311
ER
PT J
AU Ni, T
Wei, G
Shen, T
Han, M
Lian, YR
Fu, HH
Luo, Y
Yang, YQ
Liu, J
Wakabayashi, Y
Li, Z
Finkel, T
Xu, H
Zhu, J
AF Ni, Ting
Wei, Gang
Shen, Ting
Han, Miao
Lian, Yaru
Fu, Haihui
Luo, Yan
Yang, Yanqin
Liu, Jie
Wakabayashi, Yoshi
Li, Zheng
Finkel, Toren
Xu, Hong
Zhu, Jun
TI MitoRCA-seq reveals unbalanced cytocine to thymine transition in Polg
mutant mice
SO SCIENTIFIC REPORTS
LA English
DT Article
ID MITOCHONDRIAL-DNA MUTATIONS; HUMAN MTDNA GENOMES; AMPLIFICATION;
HETEROPLASMY; POLYMERASE; FIDELITY; DISEASE
AB Mutations in mitochondrial DNA (mtDNA) can lead to a wide range of human diseases. We have developed a deep sequencing strategy, mitoRCA-seq, to detect low-frequency mtDNA point mutations starting with as little as 1 ng of total DNA. It employs rolling circle amplification, which enriches the full-length circular mtDNA by either custom mtDNA-specific primers or a commercial kit, and minimizes the contamination of nuclear encoded mitochondrial DNA (Numts). By analyzing the mutation profiles of wild-type and Polg (mitochondrial DNA polymerase gamma) mutant mice, we found that mice with the proofreading deficient mtDNA polymerase have a significantly higher mutation load by expanding the number of mutation sites and to a lesser extent by elevating the mutation frequency at existing sites even before the premature aging phenotypes appear. Strikingly, cytocine (C) to thymine (T) transitions are found to be overrepresented in the mtDNA of Polg mutated mice. The C -> T transition, compared to other types of mutations, tends to increase the hydrophobicity of the underlying amino acids, and may contribute to the impaired protein function of the Polg mutant mice. Taken together, our findings may provide clues to further investigate the molecular mechanism underlying premature aging phenotype in Polg mutant mice.
C1 [Ni, Ting; Wei, Gang; Shen, Ting; Han, Miao; Lian, Yaru; Fu, Haihui] Fudan Univ, Sch Life Sci, Collaborat Innovat Ctr Genet & Dev, State Key Lab Genet Engn, Shanghai 200438, Peoples R China.
[Ni, Ting; Wei, Gang; Shen, Ting; Han, Miao; Lian, Yaru; Fu, Haihui] Fudan Univ, Sch Life Sci, Collaborat Innovat Ctr Genet & Dev, MOE Key Lab Contemporary Anthropol,Minist Educ, Shanghai 200438, Peoples R China.
[Ni, Ting; Luo, Yan; Yang, Yanqin; Wakabayashi, Yoshi; Xu, Hong; Zhu, Jun] NHLBI, Genet & Dev Biol Ctr, NIH, Bethesda, MD 20892 USA.
[Liu, Jie; Finkel, Toren] NHLBI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Li, Zheng] NIMH, Unit Synapse Dev & Plast, NIH, Bethesda, MD 20892 USA.
RP Ni, T (reprint author), Fudan Univ, Sch Life Sci, Collaborat Innovat Ctr Genet & Dev, State Key Lab Genet Engn, Shanghai 200438, Peoples R China.
EM tingni@fudan.edu.cn; jun.zhu@nih.gov
RI Xu, Hong/H-9997-2016
OI Xu, Hong/0000-0003-1049-1184
FU Division of Intramural Research of National Heart Lung and Blood
Institute (USA); National Key Basic Research Program of China (973
program) [2013CB530700]; National Science Foundation of China
[31471192]; Shanghai Pujiang Talent Plan [13PJ1400700]; Thousand Talents
Plan and Research and Innovation Project of Shanghai Municipal Education
Commission [14ZZ007]
FX We thank Dr. Neal Epstein for critical reading of the manuscript. This
work was supported by the Division of Intramural Research of National
Heart Lung and Blood Institute (USA), National Key Basic Research
Program of China (973 program: 2013CB530700), National Science
Foundation of China (31471192), Shanghai Pujiang Talent Plan
(13PJ1400700), the Thousand Talents Plan and Research and Innovation
Project of Shanghai Municipal Education Commission (14ZZ007).
NR 36
TC 0
Z9 0
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 JUL 27
PY 2015
VL 5
AR 12049
DI 10.1038/srep12049
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN6JB
UT WOS:000358540000001
PM 26212336
ER
PT J
AU Fee, E
AF Fee, Elizabeth
TI Signing the US Medicare Act: a long political struggle
SO LANCET
LA English
DT Editorial Material
C1 Natl Lib Med, Bethesda, MD 20894 USA.
RP Fee, E (reprint author), Natl Lib Med, Bethesda, MD 20894 USA.
EM feee@mail.nih.gov
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 0140-6736
EI 1474-547X
J9 LANCET
JI Lancet
PD JUL 25
PY 2015
VL 386
IS 9991
BP 332
EP 333
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA CN5CX
UT WOS:000358448400012
PM 26227457
ER
PT J
AU Lichnerova, K
Kaniakova, M
Park, SP
Skrenkova, K
Wang, YX
Petralia, RS
Suh, YH
Horak, M
AF Lichnerova, Katarina
Kaniakova, Martina
Park, Seung Pyo
Skrenkova, Kristyna
Wang, Ya-Xian
Petralia, Ronald S.
Suh, Young Ho
Horak, Martin
TI Two N-glycosylation Sites in the GluN1 Subunit Are Essential for
Releasing N-methyl-D-aspartate (NMDA) Receptors from the Endoplasmic
Reticulum
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID AMINO-TERMINAL DOMAIN; CELL-SURFACE EXPRESSION; ER RETENTION SIGNAL;
FUNCTIONAL EXPRESSION; SUBTYPE-DEPENDENCE; NR2 SUBUNITS; TRAFFICKING;
BINDING; MODULATION; DELIVERY
AB NMDA receptors (NMDARs) comprise a subclass of neurotransmitter receptors whose surface expression is regulated at multiple levels, including processing in the endoplasmic reticulum (ER), intracellular trafficking via the Golgi apparatus, internalization, recycling, anddegradation. With respect to early processing, NMDARs are regulated by the availability of GluN subunits within the ER, the presence of ER retention and export signals, and post translational modifications, including phosphorylation and palmitoylation. However, the role of N-glycosylation, one of the most common posttranslational modifications, in regulating NMDAR processing has not been studied in detail. Using biochemistry, confocal and electron microscopy, and electrophysiology in conjunction with a lentivirus-based molecular replacement strategy, we found that NMDARs are released from the ER only when two asparagine residues in the GluN1 subunit (Asn-203 and Asn-368) are N-glycosylated. Although the GluN2A and GluN2B subunits are also N-glycosylated, their N-glycosylation sites do not appear to be essential for surface delivery of NMDARs. Furthermore, we found that removing N-glycans from native NMDAR saltered the receptor affinity for glutamate. Our results suggest a novel mechanism by which neurons ensure that postsynaptic membranes contain sufficient numbers of functional NMDARs.
C1 [Lichnerova, Katarina; Kaniakova, Martina; Skrenkova, Kristyna; Horak, Martin] Acad Sci Czech Republ Vvi, Inst Physiol, Prague 14220 4, Czech Republic.
[Lichnerova, Katarina] Charles Univ Prague, Dept Physiol, Fac Sci, Prague 12843 2, Czech Republic.
[Park, Seung Pyo; Suh, Young Ho] Seoul Natl Univ, Coll Med, Dept Biomed Sci, Neurosci Res Inst, Seoul 110799, South Korea.
[Wang, Ya-Xian; Petralia, Ronald S.] NIDCD, Adv Imaging Core, NIH, Bethesda, MD 20892 USA.
RP Suh, YH (reprint author), Seoul Natl Univ, Coll Med, Dept Biomed Sci, 103 Daehak Ro, Seoul 110799, South Korea.
EM suhyho@snu.ac.kr; mhorak@biomed.cas.cz
RI Horak, Martin/F-9819-2010; Kaniakova, Martina/C-2593-2012
FU Grant Agency of the Czech Republic [14-02219S]; Marie Curie
International Reintegration Grant [PIRG-GA-2010-276827]; Grant Agency of
Charles University [1520-243-253483]; Research Project of the AS CR
[RVO:67985823]; BIOCEV/Biotechnology and Biomedicine Center of Academy
of Sciences; Charles University in Vestec; European Regional Development
Fund; NIDCD/National Institutes of Health; National Research Foundation
of Korea - Ministry of Science, ICT, and Future Planning [2011-0011694]
FX This work was supported by project 14-02219S from the Grant Agency of
the Czech Republic (to M. H., K. L., M. K., and K. S.), Marie Curie
International Reintegration Grant PIRG-GA-2010-276827 (to M. H.), Grant
Agency of Charles University Grant 1520-243-253483 (to K. L.), and the
Research Project of the AS CR RVO:67985823 and BIOCEV/Biotechnology and
Biomedicine Center of Academy of Sciences and Charles University in
Vestec (project supported by the European Regional Development Fund (to
M. H., K. L., and K. S.). The authors declare that they have no
conflicts of interest with the contents of this article.; Supported by
the Intramural Research Program of the NIDCD/National Institutes of
Health.; Supported by the Basic Science Research Program through the
National Research Foundation of Korea funded by the Ministry of Science,
ICT, and Future Planning (2011-0011694). To whom correspondence may be
addressed: Dept. of Biomedical Sciences, Seoul National University
College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 110-799, South
Korea. E-mail: suhyho@snu.ac.kr.
NR 45
TC 7
Z9 7
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 JUL 24
PY 2015
VL 290
IS 30
BP 18379
EP 18390
DI 10.1074/jbc.M115.656546
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CN5ZE
UT WOS:000358512100011
PM 26045554
ER
PT J
AU Rostovtseva, TK
Gurnev, PA
Protchenko, O
Hoogerheide, DP
Yap, TL
Philpott, CC
Lee, JC
Bezrukov, SM
AF Rostovtseva, Tatiana K.
Gurnev, Philip A.
Protchenko, Olga
Hoogerheide, David P.
Yap, Thai Leong
Philpott, Caroline C.
Lee, Jennifer C.
Bezrukov, Sergey M.
TI alpha-Synuclein Shows High Affinity Interaction with Voltage-dependent
Anion Channel, Suggesting Mechanisms of Mitochondrial Regulation and
Toxicity in Parkinson Disease
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID PERMEABILITY TRANSITION PORE; OUTER-MEMBRANE; COMPLEX-I;
ALZHEIMERS-DISEASE; FIBRIL FORMATION; INNER MEMBRANE; CANCER-CELLS; LEWY
BODIES; VDAC; PROTEIN
AB Participation of the small, intrinsically disordered protein alpha-synuclein (alpha-syn) in Parkinson disease (PD) pathogenesis has been well documented. Although recent research demonstrates the involvement of alpha-syn in mitochondrial dysfunction in neurodegeneration and suggests direct interaction of alpha-syn with mitochondria, the molecular mechanism(s) of alpha-syn toxicity and its effect on neuronal mitochondria remain vague. Here we report that at nanomolar concentrations, alpha-syn reversibly blocks the voltage-dependent anion channel (VDAC), the major channel of the mitochondrial outer membrane that controls most of the metabolite fluxes in and out of the mitochondria. Detailed analysis of the blockage kinetics of VDAC reconstituted into planar lipid membranes suggests that alpha-syn is able to translocate through the channel and thus target complexes of the mitochondrial respiratory chain in the inner mitochondrial membrane. Supporting our in vitro experiments, a yeast model of PD shows that alpha-syn toxicity in yeast depends on VDAC. The functional interactions between VDAC and alpha-syn, revealed by the present study, point toward the long sought after physiological and pathophysiological roles for monomeric alpha-syn in PD and in other alpha-synucleinopathies.
C1 [Rostovtseva, Tatiana K.; Gurnev, Philip A.; Hoogerheide, David P.; Bezrukov, Sergey M.] Eunice Kennedy Shriver NICHD, Program Phys Biol, NIH, Bethesda, MD 20892 USA.
[Gurnev, Philip A.] Univ Massachusetts, Dept Phys, Amherst, MA 01003 USA.
[Protchenko, Olga; Philpott, Caroline C.] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
[Hoogerheide, David P.] NIST, Ctr Neutron Res, Gaithersburg, MD 20899 USA.
[Yap, Thai Leong; Lee, Jennifer C.] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA.
RP Rostovtseva, TK (reprint author), Eunice Kennedy Shriver NICHD, Program Phys Biol, NIH, 9000 Rockville Pike,Bldg 9,Rm 1E-106, Bethesda, MD 20892 USA.
EM rostovtt@mail.nih.gov
RI Lee, Jennifer/E-9658-2015; Regan, Clinton/E-6250-2012
OI Lee, Jennifer/0000-0003-0506-8349;
FU National Institutes of Health (NIH); Eunice Kennedy Shriver NICHD;
NIDDK; NHLBI; National Science Foundation EAGER [1249199]; National
Research Council at the National Institute of Standards and Technology;
National Institutes of Health
FX This work was supported, in whole or in part, by the Intramural Research
Program of the National Institutes of Health (NIH), Eunice Kennedy
Shriver NICHD, NIDDK, and NHLBI. The authors declare that they have no
conflicts of interest with the contents of this article.; Supported by
National Science Foundation EAGER Award 1249199.; Recipient of a
National Research Council Research Associateship Award at the National
Institute of Standards and Technology and the National Institutes of
Health.
NR 77
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U1 5
U2 16
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 JUL 24
PY 2015
VL 290
IS 30
BP 18467
EP 18477
DI 10.1074/jbc.M115.641746
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CN5ZE
UT WOS:000358512100018
PM 26055708
ER
PT J
AU Kuznetsova, E
Nocek, B
Brown, G
Makarova, KS
Flick, R
Wolf, YI
Khusnutdinova, A
Evdokimova, E
Jin, K
Tan, K
Hanson, AD
Hasnain, G
Zallot, R
de Crecy-Lagard, V
Babu, M
Savchenko, A
Joachimiak, A
Edwards, AM
Koonin, EV
Yakunin, AF
AF Kuznetsova, Ekaterina
Nocek, Boguslaw
Brown, Greg
Makarova, Kira S.
Flick, Robert
Wolf, Yuri I.
Khusnutdinova, Anna
Evdokimova, Elena
Jin, Ke
Tan, Kemin
Hanson, Andrew D.
Hasnain, Ghulam
Zallot, Remi
de Crecy-Lagard, Valerie
Babu, Mohan
Savchenko, Alexei
Joachimiak, Andrzej
Edwards, Aled M.
Koonin, Eugene V.
Yakunin, Alexander F.
TI Functional Diversity of Haloacid Dehalogenase Superfamily Phosphatases
from Saccharomyces cerevisiae BIOCHEMICAL, STRUCTURAL, AND EVOLUTIONARY
INSIGHTS
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID ESCHERICHIA-COLI; PROTEIN PHOSPHATASE; BUDDING YEAST; GENE ENCODES;
MITOCHONDRIAL PHOSPHATASE; SUBSTRATE SPECIFICITIES; PHOSPHORYLATION
SITES; ALKALINE-PHOSPHATASE; THIAMIN BIOSYNTHESIS; ENZYME PROMISCUITY
AB The haloacid dehalogenase (HAD)-like enzymes comprise a large superfamily of phosphohydrolases present in all organisms. The Saccharomyces cerevisiae genome encodes at least 19 soluble HADs, including 10 uncharacterized proteins. Here, we biochemically characterized 13 yeast phosphatases from the HAD superfamily, which includes both specific and promiscuous enzymes active against various phosphorylated metabolites and peptides with several HADs implicated in detoxification of phosphorylated compounds and pseudouridine. The crystal structures of four yeast HADs provided insight into their active sites, whereas the structure of the YKR070W dimer in complex with substrate revealed a composite substrate-binding site. Although the S. cerevisiae and Escherichia coli HADs share low sequence similarities, the comparison of their substrate profiles revealed seven phosphatases with common preferred substrates. The cluster of secondary substrates supporting significant activity of both S. cerevisiae and E. coli HADs includes 28 common metabolites that appear to represent the pool of potential activities for the evolution of novel HAD phosphatases. Evolution of novel substrate specificities of HAD phosphatases shows no strict correlation with sequence divergence. Thus, evolution of the HAD superfamily combines the conservation of the overall substrate pool and the substrate profiles of some enzymes with remarkable biochemical and structural flexibility of other superfamily members.
C1 [Edwards, Aled M.] Univ Toronto, Struct Genom Consortium, Toronto, ON M5G 1L7, Canada.
[Nocek, Boguslaw; Tan, Kemin; Joachimiak, Andrzej; Edwards, Aled M.] Argonne Natl Lab, Midwest Ctr Struct Genom & Struct Biol Ctr, Biosci Div, Argonne, IL 60439 USA.
[Brown, Greg; Flick, Robert; Khusnutdinova, Anna; Evdokimova, Elena; Savchenko, Alexei; Yakunin, Alexander F.] Univ Toronto, Dept Chem Engn & Appl Chem, Toronto, ON M5S 3E5, Canada.
[Makarova, Kira S.; Wolf, Yuri I.; Koonin, Eugene V.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
[Jin, Ke; Babu, Mohan] Univ Regina, Dept Biochem, Res & Innovat Ctr, Regina, SK S4S 0A2, Canada.
[Hanson, Andrew D.; Hasnain, Ghulam; Zallot, Remi; de Crecy-Lagard, Valerie; Babu, Mohan] Univ Florida, Dept Hort Sci, Dept Microbiol & Cell Sci, Gainesville, FL 32611 USA.
RP Yakunin, AF (reprint author), Univ Toronto, Dept Chem Engn & Appl Chem, 200 Coll St, Toronto, ON M5S 3E5, Canada.
EM a.iakounine@utoronto.ca
RI ZALLOT, Remi/D-3933-2014; Regan, Clinton/E-6250-2012;
OI ZALLOT, Remi/0000-0002-7317-1578; Yakunin, Alexander/0000-0003-0813-6490
FU National Institutes of Health [GM094585]; Government of Canada through
Genome Canada; Ontario Genomics Institute; Ontario Research Fund
[2009-OGI-ABC-1405, ORF-GL2-01-004]; United States Department of Energy,
Office of Biological and Environmental Research [DE-AC02-06CH11357]; U.
S. National Science Foundation [IOS-1025398]
FX This work was supported, in whole or in part, by National Institutes of
Health Grant GM094585 (to A. J.). This work was also supported by the
Government of Canada through Genome Canada, the Ontario Genomics
Institute, and the Ontario Research Fund (Grants 2009-OGI-ABC-1405 and
ORF-GL2-01-004 to A. F. Y.), by the United States Department of Energy,
Office of Biological and Environmental Research, under Contract
DE-AC02-06CH11357 (to A. J.), and by U. S. National Science Foundation
Grant IOS-1025398 (to A. D. H.). The authors declare that they have no
conflict of interest with the content of this article.
NR 133
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U2 20
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 JUL 24
PY 2015
VL 290
IS 30
BP 18678
EP 18698
DI 10.1074/jbc.M115.657916
PG 21
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CN5ZE
UT WOS:000358512100037
PM 26071590
ER
PT J
AU Orly, G
Manor, U
Gov, NS
AF Orly, Gilad
Manor, Uri
Gov, Nir S.
TI A Biophysical Model for the Staircase Geometry of Stereocilia
SO PLOS ONE
LA English
DT Article
ID HAIR-CELL STEREOCILIA; ACTIN-FILAMENTS; BIRD COCHLEA; MECHANOELECTRICAL
TRANSDUCTION; LOCALIZATION; ELONGATION; HEARING; LENGTHS; ESPIN;
PROTRUSIONS
AB Cochlear hair cell bundles, made up of 10s to 100s of individual stereocilia, are essential for hearing, and even relatively minor structural changes, due to mutations or injuries, can result in total deafness. Consistent with its specialized role, the staircase geometry (SCG) of hair cell bundles presents one of the most striking, intricate, and precise organizations of actin-based cellular shapes. Composed of rows of actin-filled stereocilia with increasing lengths, the hair cell's staircase-shaped bundle is formed from a progenitor field of smaller, thinner, and uniformly spaced microvilli with relatively invariant lengths. While recent genetic studies have provided a significant increase in information on the multitude of stereocilia protein components, there is currently no model that integrates the basic physical forces and biochemical processes necessary to explain the emergence of the SCG. We propose such a model derived from the biophysical and biochemical characteristics of actin-based protrusions. We demonstrate that polarization of the cell's apical surface, due to the lateral polarization of the entire epithelial layer, plays a key role in promoting SCG formation. Furthermore, our model explains many distinct features of the manifestations of SCG in different species and in the presence of various deafness-associated mutations.
C1 [Orly, Gilad; Gov, Nir S.] Weizmann Inst Sci, Dept Chem Phys, IL-76100 Rehovot, Israel.
[Manor, Uri] NIH, Sect Organelle Biol, Bethesda, MD 20892 USA.
RP Gov, NS (reprint author), Weizmann Inst Sci, Dept Chem Phys, POB 26, IL-76100 Rehovot, Israel.
EM nir.gov@weizmann.ac.il
NR 42
TC 1
Z9 1
U1 1
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 24
PY 2015
VL 10
IS 7
AR e0127926
DI 10.1371/journal.pone.0127926
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN7NT
UT WOS:000358622000002
PM 26207893
ER
PT J
AU Read, KB
Sheehan, JR
Huerta, MF
Knecht, LS
Mork, JG
Humphreys, BL
AF Read, Kevin B.
Sheehan, Jerry R.
Huerta, Michael F.
Knecht, Lou S.
Mork, James G.
Humphreys, Betsy L.
CA NIH Big Data Annotator Grp
TI Sizing the Problem of Improving Discovery and Access to NIH-Funded Data:
A Preliminary Study
SO PLOS ONE
LA English
DT Article
ID PUBLICATION
AB Objective
This study informs efforts to improve the discoverability of and access to biomedical datasets by providing a preliminary estimate of the number and type of datasets generated annually by research funded by the U.S. National Institutes of Health (NIH). It focuses on those datasets that are "invisible" or not deposited in a known repository.
Methods
We analyzed NIH-funded journal articles that were published in 2011, cited in PubMed and deposited in PubMed Central (PMC) to identify those that indicate data were submitted to a known repository. After excluding those articles, we analyzed a random sample of the remaining articles to estimate how many and what types of invisible datasets were used in each article.
Results
About 12% of the articles explicitly mention deposition of datasets in recognized repositories, leaving 88% that are invisible datasets. Among articles with invisible datasets, we found an average of 2.9 to 3.4 datasets, suggesting there were approximately 200,000 to 235,000 invisible datasets generated from NIH-funded research published in 2011. Approximately 87% of the invisible datasets consist of data newly collected for the research reported; 13% reflect reuse of existing data. More than 50% of the datasets were derived from live human or non-human animal subjects.
Conclusion
In addition to providing a rough estimate of the total number of datasets produced per year by NIH-funded researchers, this study identifies additional issues that must be addressed to improve the discoverability of and access to biomedical research data: the definition of a "dataset," determination of which (if any) data are valuable for archiving and preservation, and better methods for estimating the number of datasets of interest. Lack of consensus amongst annotators about the number of datasets in a given article reinforces the need for a principled way of thinking about how to identify and characterize biomedical datasets.
C1 [Read, Kevin B.] NYU, Langone Med Ctr, Med Lib, New York, NY 11201 USA.
[Sheehan, Jerry R.; Huerta, Michael F.; Knecht, Lou S.; Mork, James G.; Humphreys, Betsy L.] NIH, Natl Lib Med, Bethesda, MD 20892 USA.
[NIH Big Data Annotator Grp] NIH, Bethesda, MD 20892 USA.
RP Read, KB (reprint author), NYU, Langone Med Ctr, Med Lib, New York, NY 11201 USA.
EM kevin.read@nyumc.org
RI Gutzman, Karen/K-7984-2013;
OI Gutzman, Karen/0000-0001-6331-4451; Read, Kevin/0000-0002-7511-9036
FU U.S. National Institutes of Health, National Library of Medicine;
National Library of Medicine
FX This research was supported by the Intramural Research Program of the
U.S. National Institutes of Health, National Library of Medicine (NLM)
and in part by an appointment to the NLM Associate Fellowship Program
sponsored by the National Library of Medicine and administered by the
Oak Ridge Institute for Science and Education.
NR 35
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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 JUL 24
PY 2015
VL 10
IS 7
AR e0132735
DI 10.1371/journal.pone.0132735
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN7NT
UT WOS:000358622000040
PM 26207759
ER
PT J
AU Girgis, HZ
AF Girgis, Hani Z.
TI Red: an intelligent, rapid, accurate tool for detecting repeats de-novo
on the genomic scale
SO BMC BIOINFORMATICS
LA English
DT Article
ID TRANSPOSABLE ELEMENTS; DNA-SEQUENCES; TANDEM REPEATS; APPROXIMATE
REPEATS; REPETITIVE ELEMENTS; EUKARYOTIC GENOMES; IDENTIFICATION;
PROGRAM; SEARCH; RETROTRANSPOSONS
AB Background: With rapid advancements in technology, the sequences of thousands of species' genomes are becoming available. Within the sequences are repeats that comprise significant portions of genomes. Successful annotations thus require accurate discovery of repeats. As species-specific elements, repeats in newly sequenced genomes are likely to be unknown. Therefore, annotating newly sequenced genomes requires tools to discover repeats de-novo. However, the currently available de-novo tools have limitations concerning the size of the input sequence, ease of use, sensitivities to major types of repeats, consistency of performance, speed, and false positive rate.
Results: To address these limitations, I designed and developed Red, applying Machine Learning. Red is the first repeat-detection tool capable of labeling its training data and training itself automatically on an entire genome. Red is easy to install and use. It is sensitive to both transposons and simple repeats; in contrast, available tools such as RepeatScout and ReCon are sensitive to transposons, and WindowMasker to simple repeats. Red performed consistently well on seven genomes; the other tools performed well only on some genomes. Red is much faster than RepeatScout and ReCon and has a much lower false positive rate than WindowMasker. On human genes with five or more copies, Red was more specific than RepeatScout by a wide margin. When tested on genomes of unusual nucleotide compositions, Red located repeats with high sensitivities and maintained moderate false positive rates. Red outperformed the related tools on a bacterial genome. Red identified 46,405 novel repetitive segments in the human genome. Finally, Red is capable of processing assembled and unassembled genomes.
Conclusions: Red's innovative methodology and its excellent performance on seven different genomes represent a valuable advancement in the field of repeats discovery.
C1 [Girgis, Hani Z.] Natl Lib Med, Natl Ctr Biotechnol Informat, Computat Biol Branch, NIH, Bethesda, MD 20894 USA.
[Girgis, Hani Z.] Univ Tulsa, Tandy Sch Comp Sci, Tulsa, OK 74104 USA.
RP Girgis, HZ (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Computat Biol Branch, NIH, 8600 Rockville Pike, Bethesda, MD 20894 USA.
EM girgishz@mail.nih.gov
NR 50
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U1 2
U2 12
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 JUL 24
PY 2015
VL 16
AR 227
DI 10.1186/s12859-015-0654-5
PG 19
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA CN4LO
UT WOS:000358401800001
PM 26206263
ER
PT J
AU Fauci, AS
Marston, HD
AF Fauci, Anthony S.
Marston, Hilary D.
TI Toward an HIV vaccine: A scientific journey
SO SCIENCE
LA English
DT Editorial Material
ID BROADLY NEUTRALIZING ANTIBODIES; MONOCLONAL-ANTIBODIES; ENVELOPE TRIMER;
EFFICACY TRIAL; INFECTION; MACAQUES; THAILAND; VIREMIA; HUMANS; POTENT
C1 [Fauci, Anthony S.] NIAID, NIH, Bethesda, MD 20892 USA.
[Marston, Hilary D.] NIAID, Global Hlth, NIH, Bethesda, MD 20892 USA.
RP Fauci, AS (reprint author), NIAID, NIH, Bethesda, MD 20892 USA.
EM afauci@niaid.nih.gov
NR 25
TC 7
Z9 7
U1 1
U2 13
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 JUL 24
PY 2015
VL 349
IS 6246
BP 386
EP 387
DI 10.1126/science.aac6300
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN4DX
UT WOS:000358381400026
PM 26206922
ER
PT J
AU Greenhill, SD
Juczewski, K
de Haan, AM
Seaton, G
Fox, K
Hardingham, NR
AF Greenhill, Stuart D.
Juczewski, Konrad
de Haan, Annelies M.
Seaton, Gillian
Fox, Kevin
Hardingham, Neil R.
TI Adult cortical plasticity depends on an early postnatal critical period
SO SCIENCE
LA English
DT Article
ID OCULAR DOMINANCE PLASTICITY; BARREL CORTEX; SOMATOSENSORY CORTEX;
EXCITATORY SYNAPSES; DISC1; SCHIZOPHRENIA; PROTEIN; RISK;
NEURODEVELOPMENT; SYNAPTOGENESIS
AB Development of the cerebral cortex is influenced by sensory experience during distinct phases of postnatal development known as critical periods. Disruption of experience during a critical period produces neurons that lack specificity for particular stimulus features, such as location in the somatosensory system. Synaptic plasticity is the agent by which sensory experience affects cortical development. Here, we describe, in mice, a developmental critical period that affects plasticity itself. Transient neonatal disruption of signaling via the C-terminal domain of "disrupted in schizophrenia 1" (DISC1)-a molecule implicated in psychiatric disorders-resulted in a lack of long-term potentiation (LTP) (persistent strengthening of synapses) and experience-dependent potentiation in adulthood. Long-term depression (LTD) (selective weakening of specific sets of synapses) and reversal of LTD were present, although impaired, in adolescence and absent in adulthood. These changes may form the basis for the cognitive deficits associated with mutations in DISC1 and the delayed onset of a range of psychiatric symptoms in late adolescence.
C1 [Greenhill, Stuart D.; de Haan, Annelies M.; Seaton, Gillian; Fox, Kevin; Hardingham, Neil R.] Cardiff Univ, Sch Biosci, Cardiff CF23 3AX, S Glam, Wales.
[Juczewski, Konrad] Natl Inst Alcohol Abuse & Alcoholism, NIH, Rockville, MD 20852 USA.
RP Hardingham, NR (reprint author), Cardiff Univ, Sch Biosci, Cardiff CF23 3AX, S Glam, Wales.
EM sbinrh@cardiff.ac.uk
OI Fox, Kevin/0000-0002-2563-112X; Greenhill, Stuart/0000-0002-5038-5258
FU UK Medical Research Council; U.S. National Institute of Mental Health,
NIH
FX We acknowledge the support of the UK Medical Research Council and U.S.
National Institute of Mental Health, NIH, to K.F. for this work. We also
thank T. Gould for histology, A. Siva for discussions on DISC1cc, and S.
Butt for suggestions on methods of tamoxifen delivery. Supplement
contains additional data.
NR 35
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U1 5
U2 23
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 JUL 24
PY 2015
VL 349
IS 6246
BP 424
EP 427
DI 10.1126/science.aaa8481
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN4DX
UT WOS:000358381400042
PM 26206934
ER
PT J
AU Lo, B
Zhang, KJ
Lu, W
Zheng, LX
Zhang, Q
Kanellopoulou, C
Zhang, Y
Liu, ZD
Fritz, JM
Marsh, R
Husami, A
Kissell, D
Nortman, S
Chaturvedi, V
Haines, H
Young, LR
Mo, J
Filipovich, AH
Bleesing, JJ
Mustillo, P
Stephens, M
Rueda, CM
Chougnet, CA
Hoebe, K
McElwee, J
Hughes, JD
Karakoc-Aydiner, E
Matthews, HF
Price, S
Su, HC
Rao, VK
Lenardo, MJ
Jordan, MB
AF Lo, Bernice
Zhang, Kejian
Lu, Wei
Zheng, Lixin
Zhang, Qian
Kanellopoulou, Chrysi
Zhang, Yu
Liu, Zhiduo
Fritz, Jill M.
Marsh, Rebecca
Husami, Ammar
Kissell, Diane
Nortman, Shannon
Chaturvedi, Vijaya
Haines, Hilary
Young, Lisa R.
Mo, Jun
Filipovich, Alexandra H.
Bleesing, Jack J.
Mustillo, Peter
Stephens, Michael
Rueda, Cesar M.
Chougnet, Claire A.
Hoebe, Kasper
McElwee, Joshua
Hughes, Jason D.
Karakoc-Aydiner, Elif
Matthews, Helen F.
Price, Susan
Su, Helen C.
Rao, V. Koneti
Lenardo, Michael J.
Jordan, Michael B.
TI Patients with LRBA deficiency show CTLA4 loss and immune dysregulation
responsive to abatacept therapy
SO SCIENCE
LA English
DT Article
ID COMMON VARIABLE IMMUNODEFICIENCY; REGULATORY T-CELLS; LONG-TERM SAFETY;
RHEUMATOID-ARTHRITIS; MUTATIONS; ACTIVATION; DISORDERS; DISEASE; GENE;
LYMPHOPROLIFERATION
AB Mutations in the LRBA gene (encoding the lipopolysaccharide-responsive and beige-like anchor protein) cause a syndrome of autoimmunity, lymphoproliferation, and humoral immune deficiency. The biological role of LRBA in immunologic disease is unknown. We found that patients with LRBA deficiency manifested a dramatic and sustained improvement in response to abatacept, a CTLA4 (cytotoxic T lymphocyte antigen-4)-immunoglobulin fusion drug. Clinical responses and homology of LRBA to proteins controlling intracellular trafficking led us to hypothesize that it regulates CTLA4, a potent inhibitory immune receptor. We found that LRBA colocalized with CTLA4 in endosomal vesicles and that LRBA deficiency or knockdown increased CTLA4 turnover, which resulted in reduced levels of CTLA4 protein in FoxP3(+) regulatory and activated conventional Tcells. In LRBA-deficient cells, inhibition of lysosome degradation with chloroquine prevented CTLA4 loss. These findings elucidate a mechanism for CTLA4 trafficking and control of immune responses and suggest therapies for diseases involving the CTLA4 pathway.
C1 [Lo, Bernice; Lu, Wei; Zheng, Lixin; Kanellopoulou, Chrysi; Fritz, Jill M.; Matthews, Helen F.; Price, Susan; Rao, V. Koneti; Lenardo, Michael J.] NIAID, Mol Dev Immune Syst Sect, NIH, Bethesda, MD 20892 USA.
[Lo, Bernice; Lu, Wei; Zheng, Lixin; Kanellopoulou, Chrysi; Fritz, Jill M.; Matthews, Helen F.; Price, Susan; Rao, V. Koneti; Lenardo, Michael J.] NIAID, Clin & Mol Genom Unit, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Lo, Bernice; Lu, Wei; Zheng, Lixin; Zhang, Qian; Kanellopoulou, Chrysi; Zhang, Yu; Fritz, Jill M.; Matthews, Helen F.; Price, Susan; Su, Helen C.; Rao, V. Koneti; Lenardo, Michael J.] NIAID, NIAID Clin Genom Program, NIH, Bethesda, MD 20892 USA.
[Zhang, Kejian; Husami, Ammar; Kissell, Diane; Nortman, Shannon] Univ Cincinnati, Dept Pediat, Div Human Genet, Cincinnati Childrens Hosp,Med Ctr, Cincinnati, OH USA.
[Zhang, Qian; Zhang, Yu; Su, Helen C.] NIAID, Human Immunol Dis Unit, Lab Host Def, NIH, Bethesda, MD 20892 USA.
[Liu, Zhiduo] NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
[Marsh, Rebecca; Chaturvedi, Vijaya; Filipovich, Alexandra H.; Bleesing, Jack J.; Jordan, Michael B.] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Div Bone Marrow Transplantat & Immune Deficiency, Dept Pediat, Cincinnati, OH 45220 USA.
[Haines, Hilary] Univ Alabama Birmingham, Div Pediat Hematol & Oncol, Dept Pediat, Birmingham, AL USA.
[Young, Lisa R.] Vanderbilt Univ, Sch Med, Div Allergy Immunol & Pulm Med, Dept Pediat, Nashville, TN 37212 USA.
[Young, Lisa R.] Vanderbilt Univ, Sch Med, Div Allergy Pulm & Crit Care, Dept Med, Nashville, TN 37212 USA.
[Mo, Jun] Univ Calif San Diego, Dept Pathol, San Diego, CA 92103 USA.
[Mo, Jun] Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA.
[Mo, Jun] Rady Childrens Hosp, San Diego, CA USA.
[Mustillo, Peter] Nationwide Childrens Hosp, Sect Allergy & Immunol, Columbus, OH USA.
[Stephens, Michael] Mayo Clin, Dept Pediat & Adolescent Med, Rochester, MN USA.
[Rueda, Cesar M.; Chougnet, Claire A.; Hoebe, Kasper; Jordan, Michael B.] Univ Cincinnati, Dept Pediat, Cincinnati Childrens Hosp Med Ctr, Div Immunobiol, Cincinnati, OH USA.
[McElwee, Joshua; Hughes, Jason D.] Merck & Co Inc, Merck Res Labs, Boston, MA USA.
[Karakoc-Aydiner, Elif] Marmara Univ, Div Pediat Allergy & Immunol, Istanbul, Turkey.
RP Jordan, MB (reprint author), Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Div Bone Marrow Transplantat & Immune Deficiency, Dept Pediat, Cincinnati, OH 45220 USA.
EM michael.jordan@cchmc.org
RI Su, Helen/H-9541-2015
OI Su, Helen/0000-0002-5582-9110
FU American Society of Hematology Bridge award; Cincinnati Children's
Hospital Medical Center Gap Award; Divisional Funds from Immunobiology
and Bone Marrow Transplantation and Immune Deficiency; Intramural
Research Program of the National Institute of Allergy and Infectious
Diseases (NIAID), NIH; Merck, Inc.; NIH [1RC2 HG005608]; Division of
Intramural Research, NIAID, NIH [1ZIAAI000769-14]
FX We thank R. Sills for patient referrals and collaborative patient care;
J. Davis, E. Smoot, and M. Similuk for clinical support; E. Jaffe and K.
Dunleavy for help with diagnosis and management of lymphoma; J. Tabacof
for patient care; I. Barlan and A. Ozen for patient referrals; S.
Ganesan, A. Morawski, and K. Lampe for technical assistance; and C.
Lucas for advice. Supported by an American Society of Hematology Bridge
award, the Cincinnati Children's Hospital Medical Center Gap Award, and
Divisional Funds from Immunobiology and Bone Marrow Transplantation and
Immune Deficiency, as well as the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases (NIAID), NIH, and
Merck, Inc. The Next Generation Mendelian Genetics project support was
provided by NIH grant 1RC2 HG005608 to D. Nickerson, J. Shendure, M.
Bamshad, and W. Raskind. The Autoimmune Lymphoproliferative Syndrome
project is also supported through the Division of Intramural Research,
NIAID, NIH, under project 1ZIAAI000769-14. The content of this
publication does not necessarily reflect the views or policies of the
U.S. Department of Health and Human Services, nor does mention of trade
names, commercial products, or organizations imply endorsement by the
U.S. government.
NR 33
TC 18
Z9 18
U1 2
U2 12
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 JUL 24
PY 2015
VL 349
IS 6246
BP 436
EP 440
DI 10.1126/science.aaa1663
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN4DX
UT WOS:000358381400045
PM 26206937
ER
PT J
AU Keck, TM
John, WS
Czoty, PW
Nader, MA
Newman, AH
AF Keck, Thomas M.
John, William S.
Czoty, Paul W.
Nader, Michael A.
Newman, Amy Hauck
TI Identifying Medication Targets for Psychostimulant Addiction: Unraveling
the Dopamine D3 Receptor Hypothesis
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID PROGRESSIVE-RATIO SCHEDULES; COCAINE-SEEKING BEHAVIOR;
POSITRON-EMISSION-TOMOGRAPHY; SUBSTANCE USE DISORDERS; MEDICINAL
CHEMISTRY PERSPECTIVE; FUNCTIONALIZED LINKING CHAINS; ABUSE THERAPEUTIC
AGENTS; D-3 RECEPTOR; PARTIAL AGONIST; DRUG-ADDICTION
AB The dopamine D3 receptor (D3R) is a target for developing medications to treat substance use disorders. D3R-selective compounds with high affinity and varying efficacies have been discovered, providing critical research tools for cell-based studies that have been translated to in vivo models of drug abuse. D3R antagonists and partial agonists have shown especially promising results in rodent models of relapse-like behavior, including stress-, drug-, and cue-induced reinstatement of drug seeking. However, to date, translation to human studies has been limited. Herein, we present an overview and illustrate some of the pitfalls and challenges of developing novel D3R-selective compounds toward clinical utility, especially for treatment of cocaine abuse. Future research and development of D3R-selective antagonists and partial agonists for substance abuse remains critically important but will also require further evaluation and development of translational animal models to determine the best time in the addiction cycle to target D3Rs for optimal therapeutic efficacy.
C1 [Keck, Thomas M.; Newman, Amy Hauck] NIDA, Med Chem Sect, Mol Targets & Medicat Discovery Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
[Keck, Thomas M.] Rowan Univ, Dept Chem & Biochem, Coll Sci & Math, Dept Biomed & Translat Sci,Sch Biomed Sci & Hlth, Glassboro, NJ 08028 USA.
[John, William S.; Czoty, Paul W.; Nader, Michael A.] Wake Forest Sch Med, Dept Physiol & Pharmacol, Winston Salem, NC 27157 USA.
RP Newman, AH (reprint author), NIDA, Med Chem Sect, Mol Targets & Medicat Discovery Branch, Intramural Res Program,NIH, 333 Cassell Dr, Baltimore, MD 21224 USA.
EM anewman@intra.nida.nih.gov
RI Keck, Thomas/G-9798-2012
OI Keck, Thomas/0000-0003-1845-9373
FU NIDA-IRP; [DA012460]; [DA010584]; [T32 AA-007565]
FX We acknowledge Jianjing Cao and Drs. Peter Grundt, Ashwini K. Banala,
and Vivek Kumar for synthetic contributions to this project. We
acknowledge Catherine Schweppe and Caitlin Burzynski for assistance in
obtaining binding data. We acknowledge Drs. Barbara Slusher and Rana
Rais for the pharmacokinetic analyses and Michael Coller and Michelle
Bell for excellent assistance in collecting data from monkeys. This work
was funded by the NIDA-IRP and grants DA012460 and DA010584. W.S.J. is
supported by T32 AA-007565.
NR 178
TC 20
Z9 20
U1 2
U2 15
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 JUL 23
PY 2015
VL 58
IS 14
BP 5361
EP 5380
DI 10.1021/jm501512b
PG 20
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA CN7OT
UT WOS:000358624600001
PM 25826710
ER
PT J
AU Garcia-Vallve, S
Guasch, L
Tomas-Hernandez, S
del Bas, JM
Ollendorff, V
Arola, L
Pujadas, G
Mulero, M
AF Garcia-Vallve, Santiago
Guasch, Laura
Tomas-Hernandez, Sarah
Maria del Bas, Josep
Ollendorff, Vincent
Arola, Lluis
Pujadas, Gerard
Mulero, Miquel
TI Peroxisome Proliferator-Activated Receptor gamma (PPAR gamma) and Ligand
Choreography: Newcomers Take the Stage
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID GENOME-WIDE; ANTIDIABETIC DRUGS; TARGETED DRUGS; GLUCOSE-UPTAKE;
ADIPOCYTE DIFFERENTIATION; TRANSACTIVATION ACTIVITY; METABOLIC DISEASES;
INSULIN-RESISTANCE; PARTIAL AGONISTS; BINDING DOMAIN
AB Thiazolidinediones (TZDs), such as rosiglitazone and pioglitazone, are peroxisome proliferator-activated receptor gamma (PPAR gamma) full agonists that have been widely used in the treatment of type 2 diabetes Mellitus. Despite the demonstrated beneficial effect of reducing glucose levels in the plasma, TZDs also induce several adverse effects. Consequently, the search for new compounds with potent antidiabetic effects but fewer undesired effects is an active field of research. Interestingly, the novel proposed Mechanisms for the antidiabetic activity of PPAR gamma agonists, consisting of PPAR gamma Ser273 phosphorylation inhibition, ligand and receptor mutual dynamics, and the presence of an alternate binding site, have recently changed the view regarding the optimal characteristics for the screening of novel PPAR gamma ligands. Furthermore, transcriptional genomics could bring essential information about the genome-wide effects of PPAR gamma ligands. Consequently, facing the new mechanistic scenario proposed for these compounds is essential for resolving the paradoxes among their agonistic function, antidiabetic activities,, and side effects and should allow the rational development of better and safer PPAR gamma-Mediated antidiabetic drugs.
C1 [Garcia-Vallve, Santiago; Tomas-Hernandez, Sarah; Pujadas, Gerard; Mulero, Miquel] Univ Rovira & Virgili, Dept Biochem & Biotechnol, Cheminformat & Nutr Grp, E-43007 Tarragona, Spain.
[Garcia-Vallve, Santiago; Maria del Bas, Josep; Arola, Lluis; Pujadas, Gerard] CEIS, TECNIO, Ctr Tecnol Nutr & Salut CTNS, Nutr & Hlth Res Grp, Reus 43204, Spain.
[Guasch, Laura] NCI, Comp Aided Drug Design Grp, Biol Chem Lab, Ctr Canc Res,NIH, Frederick, MD 21702 USA.
[Ollendorff, Vincent] INRA, Dynam Musculaire & Metab UMR866, F-34060 Montpellier, France.
[Ollendorff, Vincent] Univ Montpellier I, F-34000 Montpellier, France.
[Ollendorff, Vincent] Univ Montpellier 2, F-34000 Montpellier, France.
[Arola, Lluis] Univ Rovira & Virgili, Dept Biochem & Biotechnol, Nutrigen Res Grp, E-43007 Tarragona, Spain.
RP Mulero, M (reprint author), Univ Rovira & Virgili, Dept Biochem & Biotechnol, Cheminformat & Nutr Grp, Campus Sescelades, E-43007 Tarragona, Spain.
EM miquel.mulero@urv.cat
RI Garcia-Vallve, Santi/A-4226-2008; del Bas, Josep /K-2327-2014; Pujadas,
Gerard/B-1457-2010; Arola, Lluis/C-6074-2011
OI Garcia-Vallve, Santi/0000-0002-0348-7497; del Bas, Josep
/0000-0002-0700-2004; Pujadas, Gerard/0000-0003-2598-8089; Arola,
Lluis/0000-0003-2767-1974
FU Spanish Government [AGL2011-25831/ALI]; ACC1O program [TECCT11-1-0012];
XRQTC from "Generalitat de Catalunya"
FX American Journal Experts edited this manuscript for English language
fluency. This study was supported by Grant AGL2011-25831/ALI from the
Spanish Government, by the ACC1O program [Grant TECCT11-1-0012], and by
grant XRQTC from "Generalitat de Catalunya".
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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 JUL 23
PY 2015
VL 58
IS 14
BP 5381
EP 5394
DI 10.1021/jm501155f
PG 14
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA CN7OT
UT WOS:000358624600002
PM 25734377
ER
PT J
AU Nelson, KM
Viswanathan, K
Dawadi, S
Duckworth, BP
Boshoff, HI
Barry, CE
Aldrich, CC
AF Nelson, Kathryn M.
Viswanathan, Kishore
Dawadi, Surendra
Duckworth, Benjamin P.
Boshoff, Helena I.
Barry, Clifton E., III
Aldrich, Courtney C.
TI Synthesis and Pharmacokinetic Evaluation of Siderophore Biosynthesis
Inhibitors for Mycobacterium tuberculosis
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID PHARMACOLOGICAL EVALUATION; ANTITUBERCULAR AGENTS; ADENYLATING ENZYMES;
IRON ACQUISITION; GENE-CLUSTER; NUCLEOSIDES; ABSORPTION; DISCOVERY;
DESIGN; GROWTH
AB MbtA Catalyzes the first committed biosynthetic step of the mycobactins; which are important virulence factors associated, with iron acquisition in Mycobacterum tuberculosis. MbtA is a, validated therapeutic target for antitubercular drug development. 5'-O[N-(Salicyl)sulfamoyl]adenosine (1) is a bisubstrate inhibitor of MbtA and exhibits exceptionally potent biochemical and antitubercular activity. However, 1 suffers from suboptimal drug disposition properties resulting in a short half-life (t(1/2)), low exposure (AUC), and low bioavailability (F). Four strategies were pursued to address these liabilities including the synthesis of prodrugs, increasing the pK(a) of the acyl-sulfonyl moiety, modulation of the lipophilicity, and strategic introduction of fluorine into 1. Complete pharmacokinetic (PK) analysis of all compounds was performed. The most successful modifications involved fluorination of the nucleoside that provided substantial improvements in t(1/2) and AUC. Increasing the pK(a) of the acyl-sulfonyl linker yielded incremental enhancements, while modulation of the lipophilicity and prodrug approaches led to substantially poorer PK parameters.
C1 [Nelson, Kathryn M.; Duckworth, Benjamin P.; Aldrich, Courtney C.] Univ Minnesota, Ctr Drug Design, Acad Hlth Ctr, Minneapolis, MN 55455 USA.
[Viswanathan, Kishore; Dawadi, Surendra; Aldrich, Courtney C.] Univ Minnesota, Dept Med Chem, Minneapolis, MN 55455 USA.
[Boshoff, Helena I.; Barry, Clifton E., III] NIAID, TB Res Sect, Bethesda, MD 20892 USA.
RP Aldrich, CC (reprint author), Univ Minnesota, Ctr Drug Design, Acad Hlth Ctr, Minneapolis, MN 55455 USA.
EM aldri015@umn.edu
RI Barry, III, Clifton/H-3839-2012
FU National Institutes of Health [RO1 AI070219]; Intramural Research
Program of the NIAID, NIH; Cancer Center Support Grant [CA-77598]
FX This work was supported by a grant from the National Institutes of
Health Grant (RO1 AI070219 to C.C.A.) and the Intramural Research
Program of the NIAID, NIH (C.E.B.). We thank Anja Meissner for
performing the Caco-2 studies and Dr. Youlin Xia from NMR center of
University of Minnesota for NMR spectroscopic analysis. Mass
spectrometric analysis was carried out in the Analytical Biochemistry
Shared Resource of the Masonic Cancer Center, University of Minnesota,
funded in part by Cancer Center Support Grant CA-77598.
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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 JUL 23
PY 2015
VL 58
IS 14
BP 5459
EP 5475
DI 10.1021/acs.jmedchem.5b00391
PG 17
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA CN7OT
UT WOS:000358624600008
PM 26110337
ER
PT J
AU Kumar, V
Yarravarapu, N
Lapinsky, DJ
Perley, D
Felts, B
Tomlinson, MJ
Vaughan, RA
Henry, LK
Lever, JR
Newman, AH
AF Kumar, Vivek
Yarravarapu, Nageswari
Lapinsky, David J.
Perley, Danielle
Felts, Bruce
Tomlinson, Michael J.
Vaughan, Roxanne A.
Henry, L. Keith
Lever, John R.
Newman, Amy Hauck
TI Novel Azido-Iodo Photoaffinity Ligands for the Human Serotonin
Transporter Based on the Selective Serotonin Reuptake Inhibitor
(S)-Citalopram
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID DOPAMINE TRANSPORTER; BINDING-SITE; IRREVERSIBLE LIGANDS; COCAINE
RECEPTOR; PROBE; ANALOGS; DESIGN; LABEL; 2-NITROIMIPRAMINE;
ANTIDEPRESSANTS
AB Three photoaffinity ligands (PALs) for the human serotonin transporter (hSERT) were synthesized based on the selective serotonin reuptake inhibitor (SSRI), (S)-citalopram (1). The classic 4-azido-3-iodo-phenyl group was appended to either the C-1 Or C-5 position of the parent molecule, with variable-length linkers, to generate ligands 15, 22, and 26: These ligands retained high to moderate affinity binding (K-i = 24-227 nM) for hSERT, as assessed by [H-3]5-HT transport inhibition. When tested against Ser438Thr hSERT, all three PALs showed dramatic rightward shifts in inhibitory potency, with K-i values ranging from 3.8 to 9.9 mu M, consistent with the role of Ser438 as a key residue for high-affinity binding of many SSRIs, including (S)-citalopram. Photoactivation studies demonstrated irreversible adduction to hSERT by all ligands, but the reduced (S)-citalopram inhibition of labeling by [I-125]15 compared to that by [I-125]22 and [I-125]26 suggests differences in binding mode(s). These radioligands will be useful for characterizing the drug protein binding interactions for (S)-citalopram at hSERT.
C1 [Kumar, Vivek; Newman, Amy Hauck] NIDA, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Yarravarapu, Nageswari; Lapinsky, David J.] Duquesne Univ, Div Pharmaceut Sci, Pittsburgh, PA 15282 USA.
[Perley, Danielle; Felts, Bruce; Tomlinson, Michael J.; Vaughan, Roxanne A.; Henry, L. Keith] Univ N Dakota, Dept Basic Sci, Sch Med & Hlth Sci, Grand Forks, ND 58202 USA.
[Newman, Amy Hauck] Univ Missouri, Dept Radiol, Columbia, MO 65212 USA.
[Lever, John R.] Harry S Truman Mem Vet Hosp, Columbia, MO 65201 USA.
RP Newman, AH (reprint author), NIDA, Med Chem Sect, Intramural Res Program, NIH, 333 Cassell Dr, Baltimore, MD 21224 USA.
EM anewman@intra.nida.nih.gov
RI Kumar, Vivek/F-6183-2016
FU National Institute on Drug Abuse Intramural Research Program; NIH
[MH098127, DA027845]; UND SMHS Seed Grant
FX Support for this research was provided by the National Institute on Drug
Abuse Intramural Research Program (A.H.N. and V.K.), NIH Grant MH098127
(D.J.L.), NIH Grant DA027845 (L.K.H. and R.A.V.), and UND SMHS Seed
Grant (L.K.H. and R.A.V.). We also acknowledge resources and facilities
provided by the Harry S. Truman Memorial Veterans' Hospital (J.R.L.). We
thank Drs. Amina Woods and Ludovic Muller for providing the HEMS and Dr.
James D. Foster, University of North Dakota, for providing the
LLCPK1 HA-tagged hSERT stable cells. This work does not
represent the views of the U.S. Department of Veterans Affairs or the
United States Government.
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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 JUL 23
PY 2015
VL 58
IS 14
BP 5609
EP 5619
DI 10.1021/acs.jmedchem.5b00682
PG 11
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA CN7OT
UT WOS:000358624600018
PM 26153715
ER
PT J
AU Hummer, G
Szabo, A
AF Hummer, Gerhard
Szabo, Attila
TI Optimal Dimensionality Reduction of Multistate Kinetic and Markov-State
Models
SO JOURNAL OF PHYSICAL CHEMISTRY B
LA English
DT Article
ID MOLECULAR-DYNAMICS SIMULATIONS; FOLDING DYNAMICS; TRANSITIONS; PATHWAYS;
ENERGY
AB We develop a systematic procedure for obtaining rate and transition matrices: that optimally describe the dynamics of aggregated superstates formed by combining (clustering or lumping) microstates. These reduced dynamical models are constructed by matching the time-dependent occupancy-number correlation functions of the superstates in the lull and aggregated systems. Identical results are obtained by using a projection operator formalism. The reduced dynamic models are exact for all times in their full non-Markovian formulation. In the approximate Markovian limit, we derive simple analytic expressions for the reduced rate or Markov transition matrices that lead to exact auto-and cross-relaxation times. These reduced Markovian models strike an optimal balance between matching the dynamics at short and long times. We also discuss how this approach can be used in a hierarchical procedure of constructing optimal superstates through aggregation of microstates. The results of the general reduced-matrix theory are illustrated with applications to simple model systems and a more complex master-equation model of peptide folding derived previously from atomistic molecular dynamics simulations. We find that the reduced models faithfully capture the dynamics of the full systems, producing substantial improvements over the common local-equilibrium approximation.
C1 [Hummer, Gerhard] Max Planck Inst Biophys, Dept Theoret Biophys, D-60438 Frankfurt, Germany.
[Szabo, Attila] Natl Inst Diabet & Digest & Kidney Dis, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Hummer, G (reprint author), Max Planck Inst Biophys, Dept Theoret Biophys, D-60438 Frankfurt, Germany.
EM gerhard.hummer@biophys.mpg.de; attilas@nih.gov
RI Hummer, Gerhard/A-2546-2013; Szabo, Attila/H-3867-2012
OI Hummer, Gerhard/0000-0001-7768-746X;
FU Max Planck Society; Intramural Research Program of the National
Institute of Diabetes and Digestive and Kidney Diseases, NIH
FX G.H. was supported by the Max Planck Society. A.S. was supported by the
Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases, NIH.
NR 26
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PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1520-6106
J9 J PHYS CHEM B
JI J. Phys. Chem. B
PD JUL 23
PY 2015
VL 119
IS 29
BP 9029
EP 9037
DI 10.1021/jp508375q
PG 9
WC Chemistry, Physical
SC Chemistry
GA CN7OM
UT WOS:000358623900023
PM 25296279
ER
PT J
AU Joshi, PK
Esko, T
Mattsson, H
Eklund, N
Gandin, I
Nutile, T
Jackson, AU
Schurmann, C
Smith, AV
Zhang, WH
Okada, Y
Stancakova, A
Faul, JD
Zhao, W
Bartz, TM
Concas, MP
Franceschini, N
Enroth, S
Vitart, V
Trompet, S
Guo, XQ
Chasman, DI
O'Connel, JR
Corre, T
Nongmaithem, SS
Chen, Y
Mangino, M
Ruggiero, D
Michela, T
Farmaki, AE
Kacprowski, T
Bjonnes, A
van der Spek, A
Wu, Y
Giri, AK
Yanek, LR
Wang, LH
Hofer, E
Rietveld, CA
McLeod, O
Cornelis, MC
Pattaro, C
Verweij, N
Baumbach, C
Abdellaoui, A
Warren, HR
Vuckovic, D
Mei, H
Bouchard, C
Perry, JRB
Cappellani, S
Mirza, SS
Benton, MC
Broeckel, U
Medland, SE
Lind, P
Malerba, G
Drong, A
Yengo, L
Bielak, LF
Zhi, DG
van der Most, PJ
Shriner, D
Magi, R
Hemani, G
Karaderi, T
Wang, ZM
Liu, T
Demuth, I
Zhao, JH
Meng, WH
Lataniotis, L
van der Laan, SW
Bradfield, JP
Wood, AR
Bonnefond, A
Ahluwalia, TS
Hall, L
Salvi, E
Yazar, S
Carstensen, L
de Haan, HG
Abney, M
Afzal, U
Allison, MA
Amin, N
Asselbergs, FW
Bakker, SJL
Barr, RG
Baumeister, SE
Benjamin, DJ
Bergmann, S
Boerwinkle, E
Bottinger, EP
Campbell, A
Chakravarti, A
Chan, YL
Chanock, SJ
Chen, C
Chen, YDI
Collins, FS
Connell, J
Correa, A
Cupples, LA
Smith, GD
Davies, G
Dorr, M
Ehret, G
Ellis, SB
Feenstra, B
Feitosa, MF
Ford, I
Fox, CS
Frayling, TM
Friedrich, N
Geller, F
Scotland, G
Gillham-Nasenya, I
Gottesman, O
Graff, M
Grodstein, F
Gu, C
Haley, C
Hammond, CJ
Harris, SE
Harris, TB
Hastie, ND
Heard-Costa, NL
Heikkila, K
Hocking, LJ
Homuth, G
Hottenga, JJ
Huang, JY
Huffman, JE
Hysi, PG
Ikram, MA
Ingelsson, E
Joensuu, A
Johansson, A
Jousilahti, P
Jukema, JW
Kahonen, M
Kamatani, Y
Kanoni, S
Kerr, SM
Khan, NM
Koellinger, P
Koistinen, HA
Kooner, MK
Kubo, M
Kuusisto, J
Lahti, J
Launer, LJ
Lea, RA
Lehne, B
Lehtimaki, T
Liewald, DCM
Lind, L
Loh, M
Lokki, ML
London, SJ
Loomis, SJ
Loukola, A
Lu, YC
Lumley, T
Lundqvist, A
Mannisto, S
Marques-Vidal, P
Masciullo, C
Matchan, A
Mathias, RA
Matsuda, K
Meigs, JB
Meisinger, C
Meitinger, T
Menni, C
Mentch, FD
Mihailov, E
Milani, L
Montasser, ME
Montgomery, G
Morrison, A
Myers, RH
Nadukuru, R
Navarro, P
Nelis, M
Nieminen, MS
Nolte, IM
O'Connor, GT
Ogunniyi, A
Padmanabhan, S
Palmas, WR
Pankow, JS
Patarcic, I
Pavani, F
Peyser, PA
Pietilainen, K
Poulter, N
Prokopenko, I
Ralhan, S
Redmond, P
Rich, SS
Rissanen, H
Robino, A
Rose, LM
Rose, R
Sala, C
Salako, B
Salomaa, V
Sarin, AP
Saxena, R
Schmidt, H
Scott, LJ
Scott, WR
Sennblad, B
Seshadri, S
Sever, P
Shrestha, S
Smith, BH
Smith, JA
Soranzo, N
Sotoodehnia, N
Southam, L
Stanton, AV
Stathopoulou, MG
Strauch, K
Strawbridge, RJ
Suderman, MJ
Tandon, N
Tang, ST
Taylor, KD
Tayo, BO
Toglhofer, AM
Tomaszewski, M
Tsernikova, N
Tuomilehto, J
Uitterlinden, AG
Vaidya, D
Vlieg, AV
van Setten, J
Vasankari, T
Vedantam, S
Vlachopoulou, E
Vozzi, D
Vuoksimaa, E
Waldenberger, M
Ware, EB
Wentworth-Shields, W
Whitfield, JB
Wild, S
Willemsen, G
Yajnik, CS
Yao, J
Zaza, G
Zhu, XF
Salem, RM
Melbye, M
Bisgaard, H
Samani, NJ
Cusi, D
Mackey, DA
Cooper, RS
Froguel, P
Pasterkamp, G
Grant, SFA
Hakonarson, H
Ferrucci, L
Scott, RA
Morris, AD
Palmer, CNA
Dedoussis, G
Deloukas, P
Bertram, L
Lindenberger, U
Berndt, SI
Lindgren, CM
Timpson, NJ
Tonjes, A
Munroe, PB
Sorensen, TIA
Rotimi, CN
Arnett, DK
Oldehinkel, AJ
Kardia, SLR
Balkau, B
Gambaro, G
Morris, AP
Eriksson, JG
Wright, MJ
Martin, NG
Hunt, SC
Starr, JM
Deary, IJ
Griffiths, LR
Tiemeier, H
Pirastu, N
Kaprio, J
Wareham, NJ
Peerusse, L
Wilson, JG
Girotto, G
Caulfield, MJ
Raitakari, O
Boomsma, DI
Gieger, C
van der Harst, P
Hicks, AA
Kraft, P
Sinisalo, J
Knekt, P
Johannesson, M
Magnusson, PKE
Hamsten, A
Schmidt, R
Borecki, IB
Vartiainen, E
Becker, DM
Bharadwaj, D
Mohlke, KL
Boehnke, M
van Duijn, CM
Sanghera, DK
Teumer, A
Zeggini, E
Metspalu, A
Gasparini, P
Ulivi, S
Ober, C
Toniolo, D
Rudan, I
Porteous, DJ
Ciullo, M
Spector, TD
Hayward, C
Dupuis, J
Loos, RJF
Wright, AF
Chandak, GR
Vollenweider, P
Shuldiner, AR
Ridker, PM
Rotter, JI
Sattar, N
Gyllensten, U
North, KE
Pirastu, M
Psaty, BM
Weir, DR
Laakso, M
Gudnason, V
Takahashi, A
Chambers, JC
Kooner, JS
Strachan, DP
Campbell, H
Hirschhorn, JN
Perola, M
Polasek, O
Wilson, JF
AF Joshi, Peter K.
Esko, Tonu
Mattsson, Hannele
Eklund, Niina
Gandin, Ilaria
Nutile, Teresa
Jackson, Anne U.
Schurmann, Claudia
Smith, Albert V.
Zhang, Weihua
Okada, Yukinori
Stancakova, Alena
Faul, Jessica D.
Zhao, Wei
Bartz, Traci M.
Concas, Maria Pina
Franceschini, Nora
Enroth, Stefan
Vitart, Veronique
Trompet, Stella
Guo, Xiuqing
Chasman, Daniel I.
O'Connel, Jeffrey R.
Corre, Tanguy
Nongmaithem, Suraj S.
Chen, Yuning
Mangino, Massimo
Ruggiero, Daniela
Traglia, Michela
Farmaki, Aliki-Eleni
Kacprowski, Tim
Bjonnes, Andrew
van der Spek, Ashley
Wu, Ying
Giri, Anil K.
Yanek, Lisa R.
Wang, Lihua
Hofer, Edith
Rietveld, Cornelius A.
McLeod, Olga
Cornelis, Marilyn C.
Pattaro, Cristian
Verweij, Niek
Baumbach, Clemens
Abdellaoui, Abdel
Warren, Helen R.
Vuckovic, Dragana
Mei, Hao
Bouchard, Claude
Perry, John R. B.
Cappellani, Stefania
Mirza, Saira S.
Benton, Miles C.
Broeckel, Ulrich
Medland, Sarah E.
Lind, PenelopeA.
Malerba, Giovanni
Drong, Alexander
Yengo, Loic
Bielak, Lawrence F.
Zhi, Degui
van der Most, Peter J.
Shriner, Daniel
Maegi, Reedik
Hemani, Gibran
Karaderi, Tugce
Wang, Zhaoming
Liu, Tian
Demuth, Ilja
Zhao, Jing Hua
Meng, Weihua
Lataniotis, Lazaros
van der Laan, Sander W.
Bradfield, Jonathan P.
Wood, Andrew R.
Bonnefond, Amelie
Ahluwalia, Tarunveer S.
Hall, LeanneM.
Salvi, Erika
Yazar, Seyhan
Carstensen, Lisbeth
de Haan, Hugoline G.
Abney, Mark
Afzal, Uzma
Allison, Matthew A.
Amin, Najaf
Asselbergs, Folkert W.
Bakker, Stephan J. L.
Barr, R. Graham
Baumeister, Sebastian E.
Benjamin, Daniel J.
Bergmann, Sven
Boerwinkle, Eric
Bottinger, Erwin P.
Campbell, Archie
Chakravarti, Aravinda
Chan, Yingleong
Chanock, Stephen J.
Chen, Constance
Chen, Y. -D. Ida
Collins, Francis S.
Connell, John
Correa, Adolfo
Cupples, L. Adrienne
Smith, George Davey
Davies, Gail
Doerr, Marcus
Ehret, Georg
Ellis, Stephen B.
Feenstra, Bjarke
Feitosa, Mary F.
Ford, Ian
Fox, Caroline S.
Frayling, Timothy M.
Friedrich, Nele
Geller, Frank
Scotland, Generation
Gillham-Nasenya, Irina
Gottesman, Omri
Graff, Misa
Grodstein, Francine
Gu, Charles
Haley, Chris
Hammond, Christopher J.
Harris, Sarah E.
Harris, Tamara B.
Hastie, Nicholas D.
Heard-Costa, Nancy L.
Heikkila, Kauko
Hocking, Lynne J.
Homuth, Georg
Hottenga, Jouke-Jan
Huang, Jinyan
Huffman, Jennifer E.
Hysi, Pirro G.
Ikram, M. Arfan
Ingelsson, Erik
Joensuu, Anni
Johansson, Asa
Jousilahti, Pekka
Jukema, J. Wouter
Kahonen, Mika
Kamatani, Yoichiro
Kanoni, Stavroula
Kerr, Shona M.
Khan, Nazir M.
Koellinger, Philipp
Koistinen, Heikki A.
Kooner, Manraj K.
Kubo, Michiaki
Kuusisto, Johanna
Lahti, Jari
Launer, Lenore J.
Lea, Rodney A.
Lehne, Benjamin
Lehtimaki, Terho
Liewald, David C. M.
Lind, Lars
Loh, Marie
Lokki, Marja-Liisa
London, Stephanie J.
Loomis, Stephanie J.
Loukola, Anu
Lu, Yingchang
Lumley, Thomas
Lundqvist, Annamari
Mannisto, Satu
Marques-Vidal, Pedro
Masciullo, Corrado
Matchan, Angela
Mathias, Rasika A.
Matsuda, Koichi
Meigs, James B.
Meisinger, Christa
Meitinger, Thomas
Menni, Cristina
Mentch, Frank D.
Mihailov, Evelin
Milani, Lili
Montasser, May E.
Montgomery, GrantW.
Morrison, Alanna
Myers, Richard H.
Nadukuru, Rajiv
Navarro, Pau
Nelis, Mari
Nieminen, Markku S.
Nolte, Ilja M.
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Toniolo, Daniela
Rudan, Igor
Porteous, David J.
Ciullo, Marina
Spector, Tim D.
Hayward, Caroline
Dupuis, Josee
Loos, Ruth J. F.
Wright, Alan F.
Chandak, Giriraj R.
Vollenweider, Peter
Shuldiner, Alan R.
Ridker, Paul M.
Rotter, Jerome I.
Sattar, Naveed
Gyllensten, Ulf
North, Kari E.
Pirastu, Mario
Psaty, Bruce M.
Weir, David R.
Laakso, Markku
Gudnason, Vilmundur
Takahashi, Atsushi
Chambers, John C.
Kooner, Jaspal S.
Strachan, David P.
Campbell, Harry
Hirschhorn, Joel N.
Perola, Markus
Polasek, Ozren
Wilson, James F.
CA BioBank Japan Project
TI Directional dominance on stature and cognition in diverse human
populations
SO NATURE
LA English
DT Article
ID GENETIC-VARIANTS; INBREEDING DEPRESSION; ASSOCIATION ANALYSIS;
QUANTITATIVE TRAITS; BLOOD-PRESSURE; INTELLIGENCE; HOMOZYGOSITY;
ARCHITECTURE; PATHWAYS; DISEASE
AB Homozygosity has long been associated with rare, often devastating, Mendelian disorders(1), and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness(2). However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power(3,4). Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 x 10(-300), 2.1 x 10(-6), 2.5 x 10(-10) and 1.8 x 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples(5,6), no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection(7), this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.
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[Koistinen, Heikki A.] Biomedicum 2U, Minerva Fdn Inst Med Res, FI-00290 Helsinki, Finland.
[Kubo, Michiaki] Lab Genotyping Dev RCfIMS, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan.
[Laakso, Markku] Univ Eastern Finland, Dept Med, FI-70210 Kuopio, Finland.
[Laakso, Markku] Kuopio Univ Hosp, FI-70210 Kuopio, Finland.
[Kuusisto, Johanna; Lahti, Jari] Univ Helsinki, Inst Behav Sci, FI-00014 Helsinki, Finland.
[Lahti, Jari] Univ Helsinki, Folkhalsan Reasearch Ctr, FI-00014 Helsinki, Finland.
[Lehtimaki, Terho] Univ Tampere, Fimlab Labs, Dept Clin Chem, FI-33520 Tampere, Finland.
[Lehtimaki, Terho] Univ Tampere, Sch Med, FI-33520 Tampere, Finland.
[Lind, Lars] Univ Hosp, Dept Med Sci, S-75185 Uppsala, Sweden.
[Lokki, Marja-Liisa; Vlachopoulou, Efthymia] Univ Helsinki, Haartman Inst, Transplantat Lab, FI-00014 Helsinki, Finland.
[London, Stephanie J.] NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Loomis, Stephanie J.] Massachusetts Eye & Ear, Ophthalmol, Boston, MA 02114 USA.
[Lumley, Thomas] Univ Auckland, Dept Stat, Auckland 1142, New Zealand.
[Lundqvist, Annamari; Rissanen, Harri; Knekt, Paul] Natl Inst Hlth & Welf, Dept Hlth Funct Capac & Welf, FI-00271 Helsinki, Finland.
[Marques-Vidal, Pedro; Vollenweider, Peter] Univ Hosp, Dept Internal Med, CH-1011 Lausanne, Switzerland.
[Matchan, Angela; Soranzo, Nicole; Southam, Lorraine; Zeggini, Eleftheria] Wellcome Trust Sanger Inst, Human Genet, Cambridge CB10 1HH, England.
[Mathias, Rasika A.] Johns Hopkins Univ, Sch Med, Dept Med, Div Allergy & Clin Immunol, Baltimore, MD 21224 USA.
[Matsuda, Koichi] Univ Tokyo, Lab Mol Med, Ctr Human Genome, Inst Med Sci,Minato Ku, Tokyo 1088639, Japan.
[Meigs, James B.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA.
[Meitinger, Thomas] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Human Genet, D-85764 Neuherberg, Germany.
[Meitinger, Thomas] Tech Univ Munich, Inst Human Genet, Klinikum Rechts Isar, D-81675 Munich, Germany.
[Montgomery, GrantW.] QIMR Berghofer Med Res Inst, Mol Epidemiol, Brisbane, Qld 4006, Australia.
[Myers, Richard H.] Boston Univ, Sch Med, Genome Sci Inst, Boston, MA 02118 USA.
[Nieminen, Markku S.; Sinisalo, Juha] Univ Helsinki, Cent Hosp, HUCH Heart & Lung Ctr, FI-00029 Helsinki, Finland.
[O'Connor, George T.] Boston Univ, Sch Med, Pulm Ctr, Boston, MA 02118 USA.
[O'Connor, George T.] Boston Univ, Dept Med, Boston, MA 02118 USA.
[Ogunniyi, Adesola; Salako, Babatunde] Univ Ibadan, Dept Med, Ibadan, Nigeria.
[Padmanabhan, Sandosh] Univ Glasgow, ICAMS, Glasgow G12 8TA, Lanark, Scotland.
[Pankow, James S.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN 55454 USA.
[Patarcic, Inga; Polasek, Ozren] Univ Split, Ctr Global Hlth, Split 21000, Croatia.
[Patarcic, Inga; Polasek, Ozren] Univ Split, Dept Publ Hlth, Sch Med, Split 21000, Croatia.
[Pietilainen, Kirsi] Univ Helsinki, Obes Res Unit, Res Programs Unit, Diabet & Obes, FI-00014 Helsinki, Finland.
[Poulter, Neil; Sever, Peter] Univ London Imperial Coll Sci Technol & Med, Int Ctr Circulatory Hlth, London W2 1LA, England.
[Prokopenko, Inga; Froguel, Philippe] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Genom Common Dis, London SW7 2AZ, England.
[Ralhan, Sarju] Hero DMC Heart Inst, Dept Cardiol & Cardio Thorac Surg, Civil Lines, Ludhiana 141001, Punjab, India.
[Rich, Stephen S.] Univ Virginia, Sch Med, Dept Publ Hlth Sci, Charlottesville, VA 22908 USA.
[Rose, Richard] Indiana Univ Bloomington, Dept Psychol & Brain Sci, Bloomington, IN 47405 USA.
[Schmidt, Helena; Toeglhofer, Anna Maria] Med Univ Graz, Inst Mol Biol & Biochem, A-8010 Graz, Austria.
[Sennblad, Bengt] Karolinska Inst, Sci Life Lab, SE-17121 Stockholm, Sweden.
[Smith, Blair H.] Univ Dundee, Dundee DD2 4DB, Scotland.
[Sotoodehnia, Nona] Univ Washington, Div Cardiol, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA.
[Stanton, Alice V.] Royal Coll Surgeons Ireland, Mol & Cellular Therapeut, Dublin 2, Ireland.
[Stathopoulou, Maria G.] UMR INSERM U1122, F-54000 Nancy, France.
[Stathopoulou, Maria G.] Univ Lorraine, INSERM, IGE PCV Interact Geneenvironm Physiopathol Cardio, F-54000 Nancy, France.
[Strauch, Konstantin] Univ Munich, Chair Genet Epidemiol, Inst Med Informat Biometry & Epidemiol, D-81377 Munich, Germany.
[Tandon, Nikhil] All India Inst Med Sci, Dept Endocrinol, New Delhi 110029, India.
ImpColl London, Natl Heart & Lung Inst, London W12 0NN, England.
[Tang, Sian-Tsun; Kooner, Jaspal S.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London W12 0NN, England.
[Tayo, Bamidele O.; Cooper, Richard S.] Loyola Univ Chicago, Stritch Sch Med, Dept Publ Hlth Sci, Maywood, IL 60153 USA.
[Tomaszewski, Maciej; Samani, Nilesh J.] Univ Leicester, Glenfield Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester LE3 9QP, Leics, England.
[Tsernikova, Natalia; Metspalu, Andres] Univ Tartu, Inst Mol & Cell Biol, EE-51010 Tartu, Estonia.
[Tuomilehto, Jaakko] Danube Univ Krems, Ctr Vasc Prevent, A-3500 Krems, Austria.
[Tuomilehto, Jaakko] King Abdulaziz Univ, Res Grp, Jeddah 21589, Saudi Arabia.
[Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands.
[Vaidya, Dhananjay] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
[Vasankari, Tuula] Finnish Lung Hlth Assoc, FI-00250 Helsinki, Finland.
[Whitfield, John B.; Martin, Nicholas G.] QIMR Berghofer Med Res Inst, Genet Epidemiol, Brisbane, Qld 4006, Australia.
[Yajnik, Chittaranjan S.] KEM Hosp & Res Ctr, Diabet Unit, Pune 411011, Maharashtra, India.
[Zaza, Gianluigi] Univ Verona, Dept Med, Renal Unit, I-37124 Verona, Italy.
[Zhu, Xiaofeng] CaseWestern Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA.
[Melbye, Mads] Stanford Univ, Dept Med, Stanford, CA 94305 USA.
[Grant, Struan F. A.; Hakonarson, Hakon] Univ Penn, Perelman Sch Med, Dept Pediat, Philadelphia, PA 19104 USA.
[Ferrucci, Luigi] NIA, Translat Gerontol Branch, Baltimore, MD 21225 USA.
[Morris, Andrew D.] Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh EH16 4UX, Midlothian, Scotland.
[Palmer, Colin N. A.] Univ Dundee, Ninewells Hosp & Sch Med, Med Res Inst, Ctr Pharmacogenet & Pharmacogen, Dundee DD1 9SY, Scotland.
[Deloukas, Panos] King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah 21589, Saudi Arabia.
[Bertram, Lars] Univ London Imperial Coll Sci Technol & Med, Fac Med, London W6 8RP, England.
[Toenjes, Anke] Univ Leipzig, Dept Med, D-04103 Leipzig, Germany.
[Sorensen, Thorkild I. A.] Bispebjerg & Frederiksberg Hosp, Inst Prevent Med, DK-2000 Copenhagen, Denmark.
[Arnett, Donna K.] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL 35294 USA.
[Oldehinkel, Albertine J.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, NL-9700 RB Groningen, Netherlands.
[Balkau, Beverley] INSERM, Epidemiol Diabet Obes & Chron Kidney Dis Lifecour, CESP Ctr Res Epidemiol & Populat Hlth, U1018, F-94807 Villejuif, France.
[Gambaro, Giovanni] Univ Cattolica Sacro Cuore, Dipartimento Sci Med, I-00168 Rome, Italy.
[Morris, Andrew P.] Univ Liverpool, Dept Biostat, Liverpool L69 3GA, Merseyside, England.
[Eriksson, Johan G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, FI-00014 Helsinki, Finland.
[Eriksson, Johan G.] Vasa Cent Hosp, FI-65130 Vaasa, Finland.
[Eriksson, Johan G.] Univ Helsinki, Folkhalsan Reasearch Ctr, FI-00014 Helsinki, Finland.
[Eriksson, Johan G.] Univ Helsinki, Cent Hosp, Unit Gen Practice, FI-00290 Helsinki, Finland.
[Wright, Margie J.] QIMR Berghofer Med Res Inst, Neuroimaging Genet, Brisbane, Qld 4006, Australia.
[Hunt, Steven C.] Univ Utah, Cardiovasc Genet Div, Salt Lake City, UT 84117 USA.
[Starr, John M.] Univ Edinburgh, Alzheimer Scotland Res Ctr, Edinburgh EH8 9JZ, Midlothian, Scotland.
[Tiemeier, Henning] Erasmus MC, Dept Psychiat, NL-3000 CA Rotterdam, Netherlands.
[Kaprio, Jaakko] Natl Inst Hlth & Welf THL, FI-00271 Helsinki, Finland.
[Perusse, Louis] Univ Laval, Dept Kinesiol, Quebec City, PQ 2300, Canada.
[Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
[Raitakari, Olli] Univ Turku, Dept Clin Physiol & Nucl Med, FI-20521 Turku, Finland.
[Raitakari, Olli] Turku Univ Hosp, FI-20521 Turku, Finland.
[Raitakari, Olli] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, FI-20521 Turku, Finland.
[van der Harst, Pim] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands.
[Johannesson, Magnus] Stockholm Sch Econ, Dept Econ, S-11383 Stockholm, Sweden.
[Magnusson, Patrik K. E.] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden.
[Borecki, Ingrid B.] Washington Univ, Sch Med, Dept Genet & Biostat, St Louis, MO 63108 USA.
[Becker, Diane M.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD 21205 USA.
[Sanghera, Dharambir K.] Univ Oklahoma, Hlth Sci Ctr, Dept Pediat, Oklahoma City, OK 73104 USA.
[Sanghera, Dharambir K.] Univ Oklahoma, Hlth Sci Ctr, Dept Pharmaceut Sci, Oklahoma City, OK 73104 USA.
[Gasparini, Paolo] Sidra Med & Res Ctr, Doha, Qatar.
[Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA.
[Chandak, Giriraj R.] Genome Inst Singapore, Singapore 138672, Singapore.
[Shuldiner, Alan R.] Univ Maryland, Sch Med, Dept Med, Program Personalised & Genom Med, Baltimore, MD 21201 USA.
[Shuldiner, Alan R.] Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21201 USA.
[Sattar, Naveed] Univ Glasgow, BHF Glasgow Cardiovasc Res Ctr, Glasgow G12 8TA, Lanark, Scotland.
[North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA.
[Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA.
[Psaty, Bruce M.] Univ Washington, Dept Epidemiol & Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98101 USA.
[Chambers, John C.; Kooner, Jaspal S.] Univ London Imperial Coll Sci Technol & Med, Imperial Coll Healthcare NHS Trust, London W2 1NY, England.
[Strachan, David P.] Univ London, Populat Hlth Res Inst, London SW17 0RE, England.
[Ahluwalia, Tarunveer S.] Steno Diabet Ctr, DK-2820 Gentofte, Denmark.
[Loh, Marie] ASTAR, Translat Lab Genet Med TLGM, Singapore 138648, Singapore.
[Wild, Sarah] Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Populat Hlth Sci, Edinburgh EH8 9AG, Midlothian, Scotland.
[Bertram, Lars] Med Univ Lubeck, Inst Neurogenet, D-23562 Lubeck, Germany.
[Bertram, Lars] Med Univ Lubeck, Inst Integrat & Expt Genom, D-23562 Lubeck, Germany.
[Bharadwaj, Dwaipayan] Jawaharlal Nehru Univ, Sch Biotechnol, New Delhi 110067, India.
RP Joshi, PK (reprint author), Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Teviot Pl, Edinburgh EH8 9AG, Midlothian, Scotland.
RI Padmanabhan, Sandosh/S-3963-2016; Bisgaard, Hans/N-4761-2016; van
Hylckama Vlieg, Astrid/A-3323-2017; Verweij, Niek/A-4499-2017;
Magnusson, Patrik/C-4458-2017; Yengo, Loic/D-2692-2017; Feitosa,
Mary/K-8044-2012; Hicks, Andrew/E-9518-2017; Colaus,
PsyColaus/K-6607-2013; Bertram, Lars/K-3889-2015; Stathopoulou,
Maria/H-7324-2016; Bouchard, Claude/A-7637-2009; Smith,
Albert/K-5150-2015; Kubo, Michiaki/N-7947-2015; ruggiero,
daniela/K-5638-2016; Schurmann, Claudia/L-1204-2016; Deloukas,
Panos/B-2922-2013; Mackey, David/H-5340-2014; Study,
GoDARTS/K-9448-2016; mangino, massimo/F-5134-2011; Kacprowski,
Tim/K-8650-2013; Waldenberger, Melanie/B-5355-2014; Johannesson,
Magnus/E-9680-2011; Gudnason, Vilmundur/K-6885-2015; Fox, Laura
/C-6249-2016; Enroth, Stefan/C-7396-2009; Wilson, James F/A-5704-2009;
Polasek, Ozren/B-6002-2011; Palmer, Colin/C-7053-2008; Meitinger,
Thomas/O-1318-2015; Marques-Vidal, Pedro/C-9449-2009; Wright,
Margaret/A-4560-2016; Kamatani, Yoichiro/N-5513-2015; Montgomery,
Grant/B-7148-2008;
OI Zeggini, Eleftheria/0000-0003-4238-659X; Verweij,
Niek/0000-0002-4303-7685; Meisinger, Christa/0000-0002-9026-6544;
Benton, Miles/0000-0003-3442-965X; Salvi, Erika/0000-0002-2724-2291;
vozzi, diego/0000-0002-2902-8184; Girotto, Giorgia/0000-0003-4507-6589;
Timpson, Nicholas/0000-0002-7141-9189; Navarro, Pau/0000-0001-5576-8584;
Padmanabhan, Sandosh/0000-0003-3869-5808; Gieger,
Christian/0000-0001-6986-9554; NUTILE, TERESA/0000-0001-7062-8352;
Loukola, Anu-Maria/0000-0003-0542-5967; van der Laan, Sander
W./0000-0001-6888-1404; Soranzo, Nicole/0000-0003-1095-3852; Koistinen,
Heikki/0000-0001-7870-070X; Bisgaard, Hans/0000-0003-4131-7592; Yengo,
Loic/0000-0002-4272-9305; Feitosa, Mary/0000-0002-0933-2410; Hicks,
Andrew/0000-0001-6320-0411; Malerba, Giovanni/0000-0001-8705-8560;
Menni, Cristina/0000-0001-9790-0571; Bertram, Lars/0000-0002-0108-124X;
Stathopoulou, Maria/0000-0003-4376-2083; Smith,
Albert/0000-0003-1942-5845; ruggiero, daniela/0000-0003-3898-7827;
Schurmann, Claudia/0000-0003-4158-9192; Deloukas,
Panos/0000-0001-9251-070X; Mackey, David/0000-0001-7914-4709; mangino,
massimo/0000-0002-2167-7470; Kacprowski, Tim/0000-0002-5393-2413;
Johansson, Asa/0000-0002-2915-4498; Pankow, James/0000-0001-7076-483X;
Griffiths, Lyn/0000-0002-6774-5475; Ware, Erin/0000-0003-4731-8158;
Sinisalo, Juha/0000-0002-0169-5137; Lahti, Jari/0000-0002-4310-5297;
Vuckovic, Dragana/0000-0001-9343-6142; London,
Stephanie/0000-0003-4911-5290; Waldenberger,
Melanie/0000-0003-0583-5093; Johannesson, Magnus/0000-0001-8759-6393;
Gudnason, Vilmundur/0000-0001-5696-0084; Enroth,
Stefan/0000-0002-5056-9137; Wilson, James F/0000-0001-5751-9178;
Polasek, Ozren/0000-0002-5765-1862; Palmer, Colin/0000-0002-6415-6560;
Marques-Vidal, Pedro/0000-0002-4548-8500; Wright,
Margaret/0000-0001-7133-4970; Montgomery, Grant/0000-0002-4140-8139;
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Medland, Sarah/0000-0003-1382-380X
FU UK Medical Research Council (MRC); MRC Human Genetics Unit "QTL in
Health and Disease" programme
FX This paper is the work of the ROHgen consortium. We thank the
participants in all ROHgen studies; cohort-specific acknowledgements are
detailed in Supplementary Table 6. This work was funded by a UK Medical
Research Council (MRC) PhD studentship to P.K.J.; and J.F.W. and O.P.
acknowledge support from the MRC Human Genetics Unit "QTL in Health and
Disease" programme. We thank W. G. Hill for discussions and comments on
the manuscript and K. Lindsay for administrative assistance.
NR 44
TC 25
Z9 25
U1 22
U2 90
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 JUL 23
PY 2015
VL 523
IS 7561
BP 459
EP U176
DI 10.1038/nature14618
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN4DD
UT WOS:000358378900036
PM 26131930
ER
PT J
AU Li, PL
Lahvic, JL
Binder, V
Pugach, EK
Riley, EB
Tamplin, OJ
Panigrahy, D
Bowman, TV
Barrett, FG
Heffner, GC
McKinney-Freeman, S
Schlaeger, TM
Daley, GQ
Zeldin, DC
Zon, LI
AF Li, Pulin
Lahvic, Jamie L.
Binder, Vera
Pugach, Emily K.
Riley, Elizabeth B.
Tamplin, Owen J.
Panigrahy, Dipak
Bowman, Teresa V.
Barrett, Francesca G.
Heffner, Garrett C.
McKinney-Freeman, Shannon
Schlaeger, Thorsten M.
Daley, George Q.
Zeldin, Darryl C.
Zon, Leonard I.
TI Epoxyeicosatrienoic acids enhance embryonic haematopoiesis and adult
marrow engraftment
SO NATURE
LA English
DT Article
ID STEM-CELLS; AORTIC ENDOTHELIUM; RNA-SEQ; ZEBRAFISH; MIGRATION; RUNX1;
TRANSPLANTATION; IDENTIFICATION; REGENERATION; TRANSITION
AB Haematopoietic stem and progenitor cell (HSPC) transplant is a widely used treatment for life-threatening conditions such as leukaemia; however, the molecular mechanisms regulating HSPC engraftment of the recipient niche remain incompletely understood. Here we develop a competitive HSPC transplant method in adult zebrafish, using in vivo imaging as a non-invasive readout. We use this system to conduct a chemical screen, and identify epoxyeicosatrienoic acids (EETs) as a family of lipids(1,2) that enhance HSPC engraftment. The pro-haematopoietic effects of EETs were conserved in the developing zebrafish embryo, where 11,12-EET promoted HSPC specification by activating a unique activator protein 1 (AP-1) and runx1 transcription program autonomous to the haemogenic endothelium. This effect required the activation of the phosphatidylinositol-3-OH kinase (PI(3) K) pathway, specifically PI(3) K gamma. In adult HSPCs, 11,12-EET induced transcriptional programs, including AP-1 activation, which modulate several cellular processes, such as migration, to promote engraftment. Furthermore, we demonstrate that the EET effects on enhancing HSPC homing and engraftment are conserved in mammals. Our study establishes a new method to explore the molecular mechanisms of HSPC engraftment, and discovers a previously unrecognized, evolutionarily conserved pathway regulating multiple haematopoietic generation and regeneration processes. EETs may have clinical application in marrow or cord blood transplantation.
C1 [Li, Pulin; Lahvic, Jamie L.; Binder, Vera; Pugach, Emily K.; Riley, Elizabeth B.; Tamplin, Owen J.; Bowman, Teresa V.; Barrett, Francesca G.; Heffner, Garrett C.; Schlaeger, Thorsten M.; Daley, George Q.; Zon, Leonard I.] Harvard Univ, Sch Med, Stem Cell Program, Boston, MA 02115 USA.
[Li, Pulin; Lahvic, Jamie L.; Binder, Vera; Pugach, Emily K.; Riley, Elizabeth B.; Tamplin, Owen J.; Bowman, Teresa V.; Barrett, Francesca G.; Heffner, Garrett C.; Schlaeger, Thorsten M.; Daley, George Q.; Zon, Leonard I.] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Haematol Oncol, Boston, MA 02115 USA.
[Li, Pulin; Lahvic, Jamie L.; Binder, Vera; Pugach, Emily K.; Riley, Elizabeth B.; Tamplin, Owen J.; Bowman, Teresa V.; Barrett, Francesca G.; Heffner, Garrett C.; Schlaeger, Thorsten M.; Daley, George Q.; Zon, Leonard I.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Li, Pulin; Zon, Leonard I.] Harvard Univ, Chem Biol Program, Cambridge, MA 02138 USA.
[Binder, Vera] Univ Munich, Dr von Hauner Childrens Hosp, Dept Hematol & Oncol, D-80337 Munich, Germany.
[Panigrahy, Dipak] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Ctr Vasc Biol Res, Boston, MA 02115 USA.
[McKinney-Freeman, Shannon] St Jude Childrens Res Hosp, Dept Haematol, Memphis, TN 38105 USA.
[Zeldin, Darryl C.] Natl Inst Environm Hlth Sci, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA.
RP Zon, LI (reprint author), Harvard Univ, Sch Med, Stem Cell Program, Boston, MA 02115 USA.
EM zon@enders.tch.harvard.edu
RI Binder, Vera/N-2078-2015
FU NIH [P50-NS40828, P30-HD18655]; HHMI; National Institutes of Health
(NIH) [R01 HL04880, P015PO1HL32262-32, 5P30 DK49216, 5R01 DK53298, 5U01
HL10001-05, R24 DK092760, 1R01HL097794-04]; Intramural Research Program
of the NIH, National Institute of Environmental Health Sciences [Z01
ES025034]; National Cancer Institute [ROCA148633-01A5]; DFG;
Care-for-Rare Foundation
FX We thank C. R. Lee, M. L. Edin and N. Gray for providing reagents; Y.
Zhou, A. Dibiase, S. Yang, S. Datta, P. Manos, R. Mathieu and M.
Ammerman for technical assistance; H. Huang for providing graphic
illustration; R. M. White, T.E. North and C. Mosimann for discussion.
Microarray studies were performed by the Molecular Genetics Core
Facility at Boston Children's Hospital, supported by NIH-P50-NS40828 and
NIH-P30-HD18655. S. Li in Y. Zhang's laboratory at the Longwood HHMI
joint core facility helped with RNA-seq. L.I.Z. and G.Q.D. are Howard
Hughes Medical Institute (HHMI) investigators. This work was supported
by HHMI and National Institutes of Health (NIH) grants R01 HL04880,
P015PO1HL32262-32, 5P30 DK49216, 5R01 DK53298, 5U01 HL10001-05, R24
DK092760, and 1R01HL097794-04 (to L.I.Z.). This work was also funded, in
part, by the Intramural Research Program of the NIH, National Institute
of Environmental Health Sciences (Z01 ES025034 to D.C.Z.), the National
Cancer Institute grant ROCA148633-01A5 (D.P.), and DFG and Care-for-Rare
Foundation (V.B.).
NR 38
TC 25
Z9 26
U1 1
U2 13
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 JUL 23
PY 2015
VL 523
IS 7561
BP 468
EP U203
DI 10.1038/nature14569
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN4DD
UT WOS:000358378900038
PM 26201599
ER
PT J
AU Lee, JM
Gordon, N
Trepel, JB
Lee, MJ
Yu, MS
Kohn, EC
AF Lee, Jung-Min
Gordon, Nicolas
Trepel, Jane B.
Lee, Min-Jung
Yu, Minshu
Kohn, Elise C.
TI Development of a multiparameter flow cytometric assay as a potential
biomarker for homologous recombination deficiency in women with
high-grade serous ovarian cancer
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Article
DE Ovarian cancer; PARP inhibitor; Biomarkers; Flow cytometry; Peripheral
blood mononuclear cells; gamma H2AX; MRE11; RAD51
ID DOUBLE-STRAND BREAKS; HISTONE H2AX PHOSPHORYLATION; DEPENDENT
NUCLEAR-DYNAMICS; INVASIVE BLADDER-CANCER; DNA-DAMAGE; MRE11 COMPLEX;
CHROMOSOMAL RADIOSENSITIVITY; LYMPHOCYTES; RADIATION; GAMMA-H2AX
AB Objectives: PARP inhibitors (PARPi) are a novel class of drugs with activity in patients with acquired or germline homologous recombination (HR) deficiency-associated high-grade serous ovarian cancer (HGSOC). We hypothesized that measuring gamma H2AX as an indicator of DNA double-strand breaks (DSB), and MRE11 or RAD51 as an indicator of DSB repair, would reflect HR status and predict response to PARPi-based therapy. Our aim was to develop and use high-throughput multiparametric flow cytometry to quantify gamma H2AX with MRE11 or RAD51 in PBMCs as a readily available surrogate.
Methods: Healthy donor PBMCs were used for assay development and optimization. We validated induction of gamma H2AX, MRE11 and RAD51 by staining with fluorophore-conjugated antibodies. The multiparameter flow cytometric method was applied to PBMC samples from recurrent HGSOC patients who were treated with PARPi, olaparib and carboplatin.
Results: Stimulation was necessary for quantification of a DNA damage response to olaparib/carboplatin in healthy donor PBMCs. The flow cytometric protocol could not distinguish between cytoplasmic and nuclear RAD51, erroneously indicating activation in response to injury. Thus, MRE11 was selected as the marker of DSB repair. PBMCs from 15 recurrent HGSOC patients were then examined. Patients who did not respond to PARPi therapy had a significantly higher pre-treatment level of gamma H2AX (p = 0.01), and a higher ratio of gamma H2AX/MRE11 (11.0 [3.5-13.2] v. 3.3 [2.8-9.9], p < 0.03) compared with responders.
Conclusions: We successfully developed and applied a multiparameter flow cytometry assay to measure gamma H2AX and MRE11 in PBMCs. Prospective studies will be required to validate this surrogate biomarker assay as a potential predictive biomarker of PARPi-based therapy.
C1 [Lee, Jung-Min; Gordon, Nicolas; Yu, Minshu; Kohn, Elise C.] NCI, Womens Malignancies Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Trepel, Jane B.; Lee, Min-Jung] NCI, Dev Therapeut Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Lee, JM (reprint author), NCI, Womens Malignancies Branch, Ctr Canc Res, 10 Ctr Dr MSC1906,Bldg 10,Room 12N-226, Bethesda, MD 20892 USA.
EM leej6@mail.nih.gov
FU NY Ovarian Cancer Research Grant of the Foundation of Women's Cancer;
Intramural Program of the Center for Cancer Research, NCI, National
Institutes of Health; Caring Together
FX This work was funded in part by the 2011-2012 Caring Together, NY
Ovarian Cancer Research Grant of the Foundation of Women's Cancer, and
by the Intramural Program of the Center for Cancer Research, NCI,
National Institutes of Health.
NR 49
TC 3
Z9 3
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1479-5876
J9 J TRANSL MED
JI J. Transl. Med.
PD JUL 22
PY 2015
VL 13
AR 239
DI 10.1186/s12967-015-0604-z
PG 12
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA CN2TS
UT WOS:000358275400003
PM 26198537
ER
PT J
AU Drame, PM
Poinsignon, A
Dechavanne, C
Cottrell, G
Farce, M
Ladekpo, R
Massougbodji, A
Cornelie, S
Courtin, D
Migot-Nabias, F
Garcia, A
Remoue, F
AF Drame, Papa M.
Poinsignon, Anne
Dechavanne, Celia
Cottrell, Gilles
Farce, Manon
Ladekpo, Rodolphe
Massougbodji, Achille
Cornelie, Sylvie
Courtin, David
Migot-Nabias, Florence
Garcia, Andre
Remoue, Franck
TI Specific antibodies to Anopheles gSG6-P1 salivary peptide to assess
early childhood exposure to malaria vector bites
SO MALARIA JOURNAL
LA English
DT Article
DE Malaria; Salivary proteins; Biomarker of exposure; Anopheles bites;
Maternal IgG transfer; Infants; Africa
ID IMMUNO-EPIDEMIOLOGIC TOOL; EVALUATING HUMAN EXPOSURE; INFECTION; AFRICA;
GAMBIAE; TRANSMISSION; ANTIGENS; MARKER; RISK; LIFE
AB Background: The estimates of risk of malaria in early childhood are imprecise given the current entomologic and parasitological tools. Thus, the utility of anti-Anopheles salivary gSG6-P1 peptide antibody responses in measuring exposure to Anopheles bites during early infancy has been assessed.
Methods: Anti-gSG6-P1 IgG and IgM levels were evaluated in 133 infants (in Benin) at three (M3), six (M6), nine (M9) and 12 (M12) months of age. Specific IgG levels were also assessed in their respective umbilical cord blood (IUCB) and maternal blood (MPB).
Results: At M3, 93.98 and 41.35% of infants had anti-gSG6-P1 IgG and IgM Ab, respectively. Specific median IgG and IgM levels gradually increased between M3 and M6 (p < 0.0001 and p < 0.001), M6-M9 (p < 0.0001 and p = 0.085) and M9-M12 (p = 0.002 and p = 0.03). These levels were positively associated with the Plasmodium falciparum infection intensity (p = 0.006 and 0.003), and inversely with the use of insecticide-treated bed nets (p = 0.003 and 0.3). Levels of specific IgG in the MPB were positively correlated to those in the IUCB (R = 0.73; p < 0.0001) and those at M3 (R = 0.34; p < 0.0001).
Conclusion: The exposure level to Anopheles bites, and then the risk of malaria infection, can be evaluated in young infants by assessing anti-gSG6-P1 IgM and IgG responses before and after 6-months of age, respectively. This tool can be useful in epidemiological evaluation and surveillance of malaria risk during the first year of life.
C1 [Drame, Papa M.; Poinsignon, Anne; Farce, Manon; Cornelie, Sylvie; Remoue, Franck] Univ Montpellier I, UMR MIVEGEC, IRD224, CNRS5290, F-34394 Montpellier, France.
[Drame, Papa M.; Poinsignon, Anne; Farce, Manon; Cornelie, Sylvie; Remoue, Franck] Univ Montpellier 2, IRD, F-34394 Montpellier, France.
[Drame, Papa M.; Remoue, Franck] Univ Montpellier I, IRD UMR MIVEGEC, IRD224, CNRS5290, Cotonou, Benin.
[Drame, Papa M.; Remoue, Franck] Univ Montpellier 2, CREC, Cotonou, Benin.
[Dechavanne, Celia; Cottrell, Gilles; Courtin, David; Migot-Nabias, Florence; Garcia, Andre] IRD, UMR Mere & Enfant Face Infect Trop 216, F-75006 Paris, France.
[Dechavanne, Celia; Courtin, David; Migot-Nabias, Florence; Garcia, Andre] Univ Paris 05, Sorbonne Paris Cite, Fac Pharm, F-75006 Paris, France.
[Cottrell, Gilles] Univ Paris 05, Lab Math Appl, F-75006 Paris, France.
[Ladekpo, Rodolphe; Massougbodji, Achille; Courtin, David] CERPAGE, Cotonou, Benin.
[Massougbodji, Achille] Univ dAbomey Calavi, Fac Sci Sante, Cotonou, Benin.
RP Drame, PM (reprint author), NIAID, Parasit Dis Lab, NIH, 4 Ctr Dr, Bethesda, MD 20892 USA.
EM papa.drame@nih.gov
RI Garcia, Andre/S-2959-2016;
OI Garcia, Andre/0000-0002-1808-472X; courtin, david/0000-0002-5263-4430;
Migot-Nabias, Florence/0000-0001-9982-594X; Dechavanne,
Celia/0000-0001-8439-9976
FU French Ministry of Foreign Affairs; IRD
FX We thank Thomas B Nutman (NIH) for the language review and re-editing of
the manuscript. We thank populations of Tori Bossito, especially women,
for their great support and collaboration. We also thank all the field
and laboratory staff for their strong commitment to this project.
Funding received from the French Ministry of Foreign Affairs and the IRD
provided all of the funds for this study.
NR 50
TC 2
Z9 2
U1 1
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1475-2875
J9 MALARIA J
JI Malar. J.
PD JUL 22
PY 2015
VL 14
AR 285
DI 10.1186/s12936-015-0800-6
PG 9
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA CN2TU
UT WOS:000358275600004
PM 26198354
ER
PT J
AU Matveeva, OV
Guo, ZS
Shabalina, SA
Chumakov, PM
AF Matveeva, Olga V.
Guo, Zong S.
Shabalina, Svetlana A.
Chumakov, Peter M.
TI Oncolysis by paramyxoviruses: multiple mechanisms contribute to
therapeutic efficiency
SO MOLECULAR THERAPY-ONCOLYTICS
LA English
DT Review
ID NEWCASTLE-DISEASE-VIRUS; FUSOGENIC MEMBRANE-GLYCOPROTEINS;
MEDULLARY-THYROID CARCINOMA; PERIPHERAL-BLOOD LEUKOCYTES; VESICULAR
STOMATITIS-VIRUS; ACTIVATED DENDRITIC CELLS; APOPTOSIS-INDUCING LIGAND;
RECOMBINANT SENDAI-VIRUS; INNATE IMMUNE-RESPONSES; NECROSIS FACTOR-ALPHA
AB Oncolytic paramyxoviruses include some strains of Measles, Mumps, Newcastle disease, and Sendai viruses. All these viruses are well equipped for promoting highly specific and efficient malignant cell death, which can be direct and/or immuno-mediated. A number of proteins that serve as natural receptors for oncolytic paramyxoviruses are frequently overexpressed in malignant cells. Therefore, the preferential interaction of paramyxoviruses with malignant cells rather than with normal cells is promoted. Due to specific genetic defects of cancer cells in the interferon (IFN) and apoptotic pathways, viral replication has the potential to be promoted specifically in tumors. Viral mediation of syncytium formation (a polykaryonic structure) promotes intratumoral paramyxovirus replication and spreading, without exposure to host neutralizing antibodies. So, two related processes: efficient intratumoral infection spread as well as the consequent mass malignant cell death, both are enhanced. In general, the paramyxoviruses elicit strong anticancer innate and adaptive immune responses by triggering multiple danger signals. The paramyxoviruses are powerful inducers of IFN and other immuno-stimulating cytokines. These viruses efficiently promote anticancer activity of natural killer cells, dendritic cells, and cytotoxic T lymphocytes. Moreover, a neuraminidase (sialidase), a component of the viral envelope of Newcastle Disease, Mumps, and Sendai viruses, can cleave sialic acids on the surface of malignant cells thereby unmasking cancer antigens and exposing them to the immune system. These multiple mechanisms contribute to therapeutic efficacy of oncolytic paramyxoviruses and are responsible for encouraging results in preclinical and clinical studies.
C1 [Matveeva, Olga V.] Biopolymer Design LLC, Acton, MA 01721 USA.
[Matveeva, Olga V.; Chumakov, Peter M.] Engelhardt Inst Mol Biol, Moscow, Russia.
[Guo, Zong S.] Univ Pittsburgh, Inst Canc, Div Surg Oncol, Pittsburgh, PA USA.
[Shabalina, Svetlana A.] Natl Inst Hlth, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
[Chumakov, Peter M.] Cleveland Clin Fdn, Lerner Res Inst, Cleveland, OH USA.
RP Matveeva, OV (reprint author), Biopolymer Design LLC, Acton, MA 01721 USA.; Matveeva, OV (reprint author), Engelhardt Inst Mol Biol, Moscow, Russia.; Shabalina, SA (reprint author), Natl Inst Hlth, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM olga.matveeva@gmail.com; shabalin@ncbi.nlm.nih.gov
FU Russian Foundation for Basic Research [11-04-00410]; Russian Scientific
Fund [14-15-01073]; Intramural Research Program of the National Library
of Medicine, NIH
FX We thank Vyacheslav M. Senin for inspiring ideas, John F. Atkins,
Dmitriy Zamarin and Anna Senina for critical reading of the manuscript.
We are grateful to Brigit Sullivan, ORS, NIH Library Writing Center, for
editing assistance. The work was supported by a grant 11-04-00410 from
the Russian Foundation for Basic Research and by a grant from Russian
Scientific Fund 14-15-01073 (P.M.C.). This research was supported in
part by the Intramural Research Program of the National Library of
Medicine, NIH.
NR 160
TC 3
Z9 3
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 2372-7705
J9 Mol Ther-Oncolytics
JI Mol. Ther.-Oncolytics
PD JUL 22
PY 2015
VL 2
AR UNSP 15011
DI 10.1038/mto.2015.11
PG 11
WC Oncology; Medicine, Research & Experimental
SC Oncology; Research & Experimental Medicine
GA EE2SB
UT WOS:000389433400002
ER
PT J
AU Bot, A
Brewer, JE
Eshhar, Z
Frankel, SR
Hickman, E
Jungbluth, AA
Morgan, R
Peretz, Y
Radvanyi, L
Ramos, CA
Robbins, PF
Wucherpfennig, KW
AF Bot, Adrian
Brewer, Joanna E.
Eshhar, Zelig
Frankel, Stanley R.
Hickman, Emma
Jungbluth, Achim A.
Morgan, Richard
Peretz, Yoav
Radvanyi, Laszlo
Ramos, Carlos A.
Robbins, Paul F.
Wucherpfennig, Kai W.
TI Target discovery for T cell therapy: next steps to advance
Immunotherapies
SO JOURNAL FOR IMMUNOTHERAPY OF CANCER
LA English
DT Article
DE Immunotherapy; Adoptive T cell therapy; Chimeric antigen receptors; T
cell receptors; Tumor infiltrating lymphocytes; Targets; Adoptive T cell
therapy; Antibodies; Vaccines
AB Investigators from academia and industry gathered on August 14, 2014, in Boston at the Inaugural ImVacS conference entitled "Target Discovery for T Cell Therapy: Next Step to Advance Immunotherapies". Novel targets, discovery strategies and enabling technologies were presented and discussed.
C1 [Bot, Adrian] Kite Pharma Inc, Translat Med, Santa Monica, CA 90404 USA.
[Brewer, Joanna E.] Adaptimmune Ltd, Cellular Biol, Abingdon, Oxon, England.
[Eshhar, Zelig] Weizmann Inst Sci, Immunol, IL-76100 Rehovot, Israel.
[Frankel, Stanley R.] Amgen Inc, Oncol Early Dev, Therapeut Area Head, Thousand Oaks, CA USA.
[Hickman, Emma] Immunocore, Target Validat, Abingdon, Oxon, England.
[Jungbluth, Achim A.] Mem Sloan Kettering Canc Ctr, Immunohistochem, Pathol, New York, NY 10021 USA.
[Morgan, Richard] Bluebird Bio, Immunotherapy, Boston, MA USA.
[Peretz, Yoav] Caprion, ImmuneCarta, Immunol, Montreal, PQ, Canada.
[Radvanyi, Laszlo] Lion Biotechnol, Woodland Hills, CA USA.
[Ramos, Carlos A.] Baylor Coll Med, Hematol Oncol Sect, Med, Houston, TX 77030 USA.
[Robbins, Paul F.] NCI, DNA Sequencing Core, Surg Branch, Bethesda, MD 20892 USA.
[Robbins, Paul F.] NCI, FACS Core, Surg Branch, Bethesda, MD 20892 USA.
[Robbins, Paul F.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
[Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Canc Immunol & AIDS, Dana Farber Canc Inst, Cambridge, MA 02138 USA.
[Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
RP Bot, A (reprint author), Kite Pharma Inc, Translat Med, 2225 Colorado Ave, Santa Monica, CA 90404 USA.
EM abot@kitepharma.com
NR 0
TC 0
Z9 0
U1 1
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2051-1426
J9 J IMMUNOTHER CANCER
JI J. Immunother. Cancer
PD JUL 21
PY 2015
VL 3
AR 31
DI 10.1186/s40425-015-0061-5
PG 5
WC Oncology
SC Oncology
GA CU7TJ
UT WOS:000363744200002
ER
PT J
AU Scheuing, L
Chiu, CT
Liao, HM
Chuang, DM
AF Scheuing, Lisa
Chiu, Chi-Tso
Liao, Hsiao-Mei
Chuang, De-Maw
TI Antidepressant mechanism of ketamine: perspective from preclinical
studies
SO FRONTIERS IN NEUROSCIENCE
LA English
DT Review
DE ketamine; NMDA antagonist; major depressive disorder; lithium; GSK-3
inhibitor; mTOR; therapeutic potential
ID GLYCOGEN-SYNTHASE KINASE-3; RESISTANT MAJOR DEPRESSION; RANDOMIZED
CONTROLLED-TRIAL; CEREBRAL CORTICAL-NEURONS; D-ASPARTATE ANTAGONIST;
ADD-ON TRIAL; NMDA RECEPTOR; BIPOLAR DEPRESSION; OXIDATIVE STRESS;
VAL66MET POLYMORPHISM
AB A debilitating mental disorder, major depressive disorder is a leading cause of global disease burden. Existing antidepressant drugs are not adequate for the majority of depressed patients, and large clinical studies have demonstrated their limited efficacy and slow response onset. Growing evidence of low-dose ketamine's rapid and potent antidepressant effects offers strong potential for future antidepressant agents. However, ketamine has considerable drawbacks such as its abuse potential, psychomimetic effects, and increased oxidative stress in the brain, thus limiting its widespread clinical use. To develop superior antidepressant drugs, it is crucial to better understand ketamine's antidepressant mechanism of action. Recent preclinical studies indicate that ketamine's antidepressant mechanism involves mammalian target of rapamycin pathway activation and subsequent synaptogenesis in the prefrontal cortex, as well as glycogen synthase kinase-3 beta (GSK-3 beta) inactivation. Adjunct GSK-3 beta inhibitors, such as lithium, can enhance ketamine's efficacy by augmenting and prolonging its antidepressant effects. Given the potential for depressive relapses, lithium in addition to ketamine is a promising solution for this clinical issue.
C1 [Scheuing, Lisa; Chiu, Chi-Tso; Liao, Hsiao-Mei; Chuang, De-Maw] NIMH, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA.
RP Chuang, DM (reprint author), NIMH, Mol Neurobiol Sect, NIH, Bldg 10,Room 3D-41,10 Ctr Dr,MSC 1363, Bethesda, MD 20892 USA.
EM chuang@mail.nih.gov
FU Intramural Research Program of the National Institute of Mental Health,
National Institutes of Health (IRP-NIMH-NIH)
FX This work was supported by the Intramural Research Program of the
National Institute of Mental Health, National Institutes of Health
(IRP-NIMH-NIH). The authors thank Peter Leeds of the NIMH, NIH for his
excellent editorial assistance. This work was written as part of the
authors' official duties as Government employees (affiliated with Annual
Report MH002468). The views expressed in this article do not necessarily
represent the views of the NIMH, NIH, HHS, nor the United States
Government.
NR 68
TC 8
Z9 8
U1 5
U2 15
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1662-453X
J9 FRONT NEUROSCI-SWITZ
JI Front. Neurosci.
PD JUL 21
PY 2015
VL 9
AR 249
DI 10.3389/fnins.2015.00249
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA CS5MC
UT WOS:000362121300001
PM 26257598
ER
PT J
AU Yuk, JM
Kim, TS
Kim, SY
Lee, HM
Han, J
Dufour, CR
Kim, JK
Jin, HS
Yang, CS
Park, KS
Lee, CH
Kim, JM
Kweon, GR
Choi, HS
Vanacker, JM
Moore, DD
Giguere, V
Jo, EK
AF Yuk, Jae-Min
Kim, Tae Sung
Kim, Soo Yeon
Lee, Hye-Mi
Han, Jeongsu
Dufour, Catherine Rosa
Kim, Jin Kyung
Jin, Hyo Sun
Yang, Chul-Su
Park, Ki-Sun
Lee, Chul-Ho
Kim, Jin-Man
Kweon, Gi Ryang
Choi, Hueng-Sik
Vanacker, Jean-Marc
Moore, David D.
Giguere, Vincent
Jo, Eun-Kyeong
TI Orphan Nuclear Receptor ERR alpha Controls Macrophage Metabolic
Signaling and A20 Expression to Negatively Regulate TLR-Induced
Inflammation
SO IMMUNITY
LA English
DT Article
ID NF-KAPPA-B; ESTROGEN-RELATED RECEPTOR; TOLL-LIKE RECEPTORS; FATTY-ACID
OXIDATION; POSTTRANSLATIONAL MODIFICATIONS; CELL-ACTIVATION; SIRTUIN 1;
ENERGY; CANCER; ENZYME
AB The orphan nuclear receptor estrogen-related receptor alpha (ERR alpha; NR3B1) is a key metabolic regulator, but its function in regulating inflammation remains largely unknown. Here, we demonstrate that ERRa negatively regulates Toll-like receptor (TLR)-induced inflammation by promoting Tnfaip3 transcription and fine-tuning of metabolic reprogramming in macrophages. ERR alpha-deficient (Esrra(-/-)) mice showed increased susceptibility to endo-toxin-induced septic shock, leading to more severe pro-inflammatory responses than control mice. ERR alpha regulated macrophage inflammatory responses by directly binding the promoter region of Tnfaip3, a deubiquitinating enzyme in TLR signaling. In addition, Esrra(-/-) macrophages showed an increased glycolysis, but impaired mitochondrial respiratory function and biogenesis. Further, ERR alpha was required for the regulation of NF-kappa B signaling by controlling p65 acetylation via maintenance of NAD(+) levels and sirtuin 1 activation. These findings unravel a previously unappreciated role for ERR alpha as a negative regulator of TLR-induced inflammatory responses through inducing Tnfaip3 transcription and controlling the metabolic reprogramming.
C1 [Yuk, Jae-Min; Kim, Tae Sung; Kim, Soo Yeon; Lee, Hye-Mi; Kim, Jin Kyung; Jin, Hyo Sun; Jo, Eun-Kyeong] Chungnam Natl Univ, Sch Med, Dept Microbiol, Taejon 301747, South Korea.
[Han, Jeongsu; Kweon, Gi Ryang] Chungnam Natl Univ, Sch Med, Dept Biochem, Taejon 301747, South Korea.
[Kim, Jin-Man] Chungnam Natl Univ, Sch Med, Dept Pathol, Taejon 301747, South Korea.
[Yuk, Jae-Min] Chungnam Natl Univ, Sch Med, Dept Infect Biol, Taejon 301747, South Korea.
[Yuk, Jae-Min; Kim, Tae Sung; Kim, Soo Yeon; Lee, Hye-Mi; Han, Jeongsu; Kim, Jin Kyung; Jin, Hyo Sun; Kim, Jin-Man; Kweon, Gi Ryang; Jo, Eun-Kyeong] Chungnam Natl Univ, Sch Med, Infect Signaling Network Res Ctr, Taejon 301747, South Korea.
[Dufour, Catherine Rosa; Giguere, Vincent] McGill Univ, Goodman Canc Res Ctr, Montreal, PQ H3A 1A3, Canada.
[Yang, Chul-Su] Hanyang Univ, Coll Sci & Technol, Dept Mol & Life Sci, Ansan 426791, South Korea.
[Park, Ki-Sun] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
[Lee, Chul-Ho] Korea Res Inst Biosci & Biotechnol, Lab Anim Resource Ctr, Taejon 305806, South Korea.
[Choi, Hueng-Sik] Chonnam Natl Univ, Sch Biol Sci & Technol, Natl Creat Res Initiat Ctr Nucl Receptor Signals, Gwangju 500757, South Korea.
[Choi, Hueng-Sik] Chonnam Natl Univ, Sch Biol Sci & Technol, Hormone Res Ctr, Gwangju 500757, South Korea.
[Vanacker, Jean-Marc] Univ Lyon 1, Inst Genom Fonct Lyon, CNRS, INRA,Ecole Normale Super Lyon, F-69364 Lyon 07, France.
[Moore, David D.] Baylor Coll Med, Dept Mol & Cell Biol, Houston, TX 77030 USA.
RP Jo, EK (reprint author), Chungnam Natl Univ, Sch Med, Dept Microbiol, Taejon 301747, South Korea.
EM hayoungj@cnu.ac.kr
FU National Research Foundation of Korea (NRF) - Korea government (MSIP)
[2007-0054932]; KRIBB Research Initiative Program [KGM4541521]; NRF -
Korean government (MSIP) [2011-0030049]; Basic Science Research Program
through the NRF - Ministry of Education [NRF-2014R1A6A1029617]; National
Creative Research Initiatives Grant through the NRF - Korean government
(Ministry of Science, ICT & Future Planning) [20110018305]; Canadian
Institutes for Health Research [MOP-111144]
FX We thank Drs. J.-S. Kim and H. Kim for critical reading of manuscript;
Drs. J.-J. Kim (Konyang University) and J.-W. Chang for excellent
technical assistance. We thank Dr. S.-H. Koo (Korea University) for
Flag-pcDNA3-hPGC1 alpha and Dr. S. Akira (Osaka University) for MyD88-
or TRIF-deficient mice. This work was supported by the National Research
Foundation of Korea (NRF) grant funded by the Korea government (MSIP)
(2007-0054932) at Chungnam National University, by a grant of KRIBB
Research Initiative Program (KGM4541521), by the NRF grant funded by the
Korean government (MSIP) (No. 2011-0030049) at Hanyang University, Basic
Science Research Program through the NRF funded by the Ministry of
Education (NRF-2014R1A6A1029617), and by a National Creative Research
Initiatives Grant (20110018305) through the NRF funded by the Korean
government (Ministry of Science, ICT & Future Planning) to H.-S.C. and
by a Canadian Institutes for Health Research grant (MOP-111144) to V.G.
NR 45
TC 11
Z9 12
U1 2
U2 13
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 JUL 21
PY 2015
VL 43
IS 1
BP 80
EP 91
DI 10.1016/j.immuni.2015.07.003
PG 12
WC Immunology
SC Immunology
GA CP7WV
UT WOS:000360101100012
PM 26200012
ER
PT J
AU Inagaki, S
Ghirlando, R
Vishnivetskiy, SA
Homan, KT
White, JF
Tesmer, JJG
Gurevich, VV
Grisshammer, R
AF Inagaki, Sayaka
Ghirlando, Rodolfo
Vishnivetskiy, Sergey A.
Homan, Kristoff T.
White, Jim F.
Tesmer, John J. G.
Gurevich, Vsevolod V.
Grisshammer, Reinhard
TI G Protein-Coupled Receptor Kinase 2 (GRK2) and 5 (GRK5) Exhibit
Selective Phosphorylation of the Neurotensin Receptor in Vitro
SO BIOCHEMISTRY
LA English
DT Article
ID MU-OPIOID RECEPTOR; BETA-GAMMA-SUBUNITS; ACIDIC AMINO-ACIDS;
COOH-TERMINAL TAIL; BETA(2)-ADRENERGIC RECEPTOR; RHODOPSIN KINASE;
BETA-2-ADRENERGIC RECEPTOR; PHOSPHOLIPID-BILAYER; MONOMERIC RHODOPSIN;
MEDIATED REGULATION
AB G protein coupled receptor kinases (GRKs) play an important role in the desensitization of G protein-mediated signaling of G protein-coupled receptors.(GPCRs). The level of interest in Mapping their phosphorylation Sites has increased because recent studies suggest that the differential pattern of receptor phosphorylation has,distinct biological consequences. In vitro phosphotylation experiments using well-controlled systems are useful for deciphering the complexity of these physiological teactions and understanding the targeted event. Here, we report on the phosphorylation of the class A GPCR neurotensin receptor 1 (NTSR1) by GRKs under defined experimental conditions afforded by nanodisc technology. Phosphorylation of NTSR1 by GRK2 was agonistdependent, whereas phosphorylation by GRK5, occurred in an activation-independent manner. In addition, the negatively charged lipids in the immediate vicinity of NM1 directly-affect phosphorylation by GRKs. Identification of phosphorylation sites in agonist-activated NTSR1 revealed that GRK2 and GRK5 target different residues located on the intracellular receptor. elements. GRK2 phosphorylates only the C-terminal Ser residues, whereas,GRK5 phosphorylates Ser and Thr residues located in intracellular loop 3 and the C-tertninus. Interestingly, phosphorylation assays using a series of NTSR1 mutants show that GRK2 does not require acidic residues upstream of the phospho-acceptors for site-specific phosphorylation, in ctintrast tO the beta(2)-adtenergic and mu-opioid receptors. Differential phosphorylation of GPCRs, by GRKS is thought to encode a particular signaling outcome, and our in vitro study revealed NTSR1 differential phosphorylation by GRK2 and GRKS.
C1 [Inagaki, Sayaka; White, Jim F.; Grisshammer, Reinhard] NINDS, Membrane Prot Struct Funct Unit, NIH, US Dept HHS, Rockville, MD 20852 USA.
[Ghirlando, Rodolfo] NIDDK, Lab Mol Biol, NIH, US Dept HHS, Bethesda, MD 20892 USA.
[Vishnivetskiy, Sergey A.; Gurevich, Vsevolod V.] Vanderbilt Univ, Dept Pharmacol, Nashville, TN 37232 USA.
[Homan, Kristoff T.; Tesmer, John J. G.] Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA.
[Homan, Kristoff T.; Tesmer, John J. G.] Univ Michigan, Dept Biol Sci, Ann Arbor, MI 48109 USA.
RP Inagaki, S (reprint author), NINDS, Membrane Prot Struct Funct Unit, NIH, US Dept HHS, Rockville, MD 20852 USA.
EM inagakisn@ninds.nih.gov; rkgriss@helix.nih.gov
RI Gurevich, Vsevolod/A-3236-2008
OI Gurevich, Vsevolod/0000-0002-3950-5351
FU Intramural Research Program of the National Institutes of Health,
National Institute of Diabetes and Digestive and Kidney Diseases;
National Institute of Neurological Disorders and Stroke; National
Institutes of Health [HL071818, GM077561]
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Diabetes and
Digestive and Kidney Diseases (R. Ghirlando), and National Institute of
Neurological Disorders and Stroke (S.I., J.F.W., and R. Grisshammer),
and by National Institutes of Health Grants HL071818 (J.J.G.T.) and
GM077561 (V.V.G.).
NR 68
TC 4
Z9 4
U1 0
U2 4
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD JUL 21
PY 2015
VL 54
IS 28
BP 4320
EP 4329
DI 10.1021/acs.biochem.5b00285
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CN6OY
UT WOS:000358555300006
PM 26120872
ER
PT J
AU Browne, P
Judson, RS
Casey, WM
Kleinstreuer, NC
Thomas, RS
AF Browne, Patience
Judson, Richard S.
Casey, Warren M.
Kleinstreuer, Nicole C.
Thomas, Russell S.
TI Screening Chemicals for Estrogen Receptor Bioactivity Using a
Computational Model
SO ENVIRONMENTAL SCIENCE & TECHNOLOGY
LA English
DT Article
ID ENDOCRINE-DISRUPTING CHEMICALS; IN-VITRO; ENVIRONMENTAL CHEMICALS;
SCIENTIFIC CONFIDENCE; TOXCAST CHEMICALS; BISPHENOL-A; TOXICITY; ASSAYS;
CELLS; PERSPECTIVES
AB The U.S. Environmental Protection Agency (EPA) is considering high-throughput and Computational Methods to evaluate the endocrine bioactivity of environmental Chemicals. Here we describe a multistep, performance-based validation of new methods and demonstrate that these new tools are sufficiently robust to be used: in the Endocrine Disruptor Screening Program (EDSP). Results from 18 estrogen receptor (ER) ToxCast high-throughput screening assays were integrated into a computational model that can discriminate bioactivity from assay-specific interference and cytetoxicity. Model scores range from 0 (no activity) to 1 (bioactivity of 17 beta-estradiol). ToxCast ER model performance was evaluated for reference chemicals, as well as results of EDSP Tier 1 screening assays in current practice. The ToxCast ER model accuracy was 86% to 93% when compared to reference chemicals and predicted results of EDSP Tier 1 guideline and other uterotrophic studies with 84% to 100% accuracy. The performance of high-throughput assays and ToxCast ER model predictions demonstrates that these methods correctly identify active and inactive reference chemical, provide a measure of relative ER bioactivity, and rapidly identify chemicals with potential endocrine bioactivities for additional Screening and testing. EPA is accepting ToxCast ER model data for 1812 chemicals as alternatives for EDSP Tier 1 ER binding,, ER transactivation, and uterotrophic assays.
C1 [Browne, Patience] US EPA, Off Chem Safety & Pollut Prevent, Washington, DC 20004 USA.
[Judson, Richard S.; Thomas, Russell S.] US EPA, Off Res & Dev, Res Triangle Pk, NC 27709 USA.
[Casey, Warren M.] NIEHS, Natl Toxicol Program, Interagcy Ctr Evaluat Alternat Toxicol Methods, Res Triangle Pk, NC 27709 USA.
[Kleinstreuer, Nicole C.] Integrated Lab Syst Inc, Natl Toxicol Program, Interagcy Ctr Evaluat Alternat Toxicol Methods, Res Triangle Pk, NC 27709 USA.
RP Browne, P (reprint author), US EPA, Off Chem Safety & Pollut Prevent, Washington, DC 20004 USA.
EM browne.patience@epa.gov
OI Thomas, Russell/0000-0002-2340-0301; Judson,
Richard/0000-0002-2348-9633; Kleinstreuer, Nicole/0000-0002-7914-3682
NR 46
TC 28
Z9 28
U1 16
U2 51
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0013-936X
EI 1520-5851
J9 ENVIRON SCI TECHNOL
JI Environ. Sci. Technol.
PD JUL 21
PY 2015
VL 49
IS 14
BP 8804
EP 8814
DI 10.1021/acs.est.5b02641
PG 11
WC Engineering, Environmental; Environmental Sciences
SC Engineering; Environmental Sciences & Ecology
GA CN6PY
UT WOS:000358557900062
PM 26066997
ER
PT J
AU Andreotti, G
Hoppin, JA
Hou, LF
Koutros, S
Gadalla, SM
Savage, SA
Lubin, J
Blair, A
Hoxha, M
Baccarelli, A
Sandler, D
Alavanja, M
Freeman, LEB
AF Andreotti, Gabriella
Hoppin, Jane A.
Hou, Lifang
Koutros, Stella
Gadalla, Shahinaz M.
Savage, Sharon A.
Lubin, Jay
Blair, Aaron
Hoxha, Mirjam
Baccarelli, Andrea
Sandler, Dale
Alavanja, Michael
Freeman, Laura E. Beane
TI Pesticide Use and Relative Leukocyte Telomere Length in the Agricultural
Health Study
SO PLOS ONE
LA English
DT Article
ID MYELODYSPLASTIC SYNDROMES; OCCUPATIONAL-EXPOSURE; OXIDATIVE STRESS;
INSECTICIDE USE; APPLICATORS; WORKERS; METAANALYSIS; LYMPHOCYTES;
CANCER; TIME
AB Some studies suggest that telomere length (TL) may be influenced by environmental exposures, including pesticides. We examined associations between occupational pesticide use reported at three time points and relative telomere length (RTL) in the Agricultural Health Study (AHS), a prospective cohort study of pesticide applicators in Iowa and North Carolina. RTL was measured by qPCR using leukocyte DNA from 568 cancer-free male AHS participants aged 31-94 years with blood samples collected between 2006 and 2008. Self-reported information, including pesticide use, was collected at three time points: enrollment (1993-1997) and two follow-up questionnaires (1998-2003, 2005-2008). For each pesticide, we evaluated cumulative use (using data from all three questionnaires), and more recent use (using data from the last follow-up questionnaire). Multivariable linear regression was used to examine the associations between pesticide use (ever, lifetime days, intensity-weighted lifetime days (lifetime days*intensity score)) and RTL, adjusting for age at blood draw and use of other pesticides. Of the 57 pesticides evaluated with cumulative use, increasing lifetime days of 2,4-D (p-trend=0.001), diazinon (p-trend=0.002), and butylate (p-trend=0.01) were significantly associated with shorter RTL, while increasing lifetime days of alachlor was significantly associated with longer RTL (p-trend=0.03). Only the association with 2,4-D was significant after adjustment for multiple comparisons. Of the 40 pesticides evaluated for recent use, malathion was associated with shorter RTL (p=0.03), and alachlor with longer RTL (p=0.03). Our findings suggest that leukocyte TL may be impacted by cumulative use and recent use of certain pesticides.
C1 [Andreotti, Gabriella; Koutros, Stella; Gadalla, Shahinaz M.; Savage, Sharon A.; Lubin, Jay; Blair, Aaron; Alavanja, Michael; Freeman, Laura E. Beane] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Hoppin, Jane A.] N Carolina State Univ, Dept Biol Sci, Raleigh, NC 27695 USA.
[Hou, Lifang] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA.
[Hou, Lifang] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA.
[Hoxha, Mirjam] Univ Milan, Dept Clin Sci & Community Hlth, Ctr Mol & Genet Epidemiol, Milan, Italy.
[Baccarelli, Andrea] Harvard Univ, Sch Publ Hlth, Exposure Epidemiol & Risk Program, Lab Environm Epigenet,Dept Environm Hlth, Boston, MA 02115 USA.
[Sandler, Dale] NIEHS, Epidemiol Branch, NIH DHHS, Res Triangle Pk, NC 27709 USA.
RP Andreotti, G (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
EM andreotg@mail.nih.gov
RI Savage, Sharon/B-9747-2015; Beane Freeman, Laura/C-4468-2015;
OI Savage, Sharon/0000-0001-6006-0740; Beane Freeman,
Laura/0000-0003-1294-4124; Baccarelli, Andrea/0000-0002-3436-0640
FU Intramural Department of National Institutes of Health
FX This work was funded by the Intramural Department of the National
Institutes of Health.
NR 34
TC 6
Z9 6
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 JUL 21
PY 2015
VL 10
IS 7
AR e0133382
DI 10.1371/journal.pone.0133382
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN6LZ
UT WOS:000358547600090
PM 26196902
ER
PT J
AU Ehler, M
Dobrosotskaya, J
Cunningham, D
Wong, WT
Chew, EY
Czaja, W
Bonner, RF
AF Ehler, Martin
Dobrosotskaya, Julia
Cunningham, Denise
Wong, Wai T.
Chew, Emily Y.
Czaja, Wojtek
Bonner, Robert F.
TI Modeling Photo-Bleaching Kinetics to Create High Resolution Maps of Rod
Rhodopsin in the Human Retina
SO PLOS ONE
LA English
DT Article
ID AGE-RELATED MACULOPATHY; FUNDUS AUTOFLUORESCENCE; MACULAR DEGENERATION;
DARK-ADAPTATION; PHOTORECEPTOR TOPOGRAPHY; GEOGRAPHIC ATROPHY;
BLOOD-VESSELS; PIGMENT; IMAGES; ELECTRORETINOGRAM
AB We introduce and describe a novel non-invasive in-vivo method for mapping local rod rhodopsin distribution in the human retina over a 30-degree field. Our approach is based on analyzing the brightening of detected lipofuscin autofluorescence within small pixel clusters in registered imaging sequences taken with a commercial 488nm confocal scanning laser ophthalmoscope (cSLO) over a 1 minute period. We modeled the kinetics of rhodopsin bleaching by applying variational optimization techniques from applied mathematics. The physical model and the numerical analysis with its implementation are outlined in detail. This new technique enables the creation of spatial maps of the retinal rhodopsin and retinal pigment epithelium (RPE) bisretinoid distribution with an approximate to 50 mu m resolution.
C1 [Ehler, Martin] Univ Vienna, Fac Math, Vienna, Austria.
[Dobrosotskaya, Julia] Case Western Reserve Univ, Dept Math Appl Math & Stat, Cleveland, OH 44106 USA.
[Cunningham, Denise] NEI, Off Clin Director, NIH, Bethesda, MD 20892 USA.
[Wong, Wai T.] NEI, Unit Neuron Glia Interact, NIH, Bethesda, MD 20892 USA.
[Chew, Emily Y.] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
[Czaja, Wojtek] Univ Maryland, Dept Math, College Pk, MD 20742 USA.
[Bonner, Robert F.] NICHHD, Sect Med Biophys, NIH, Bethesda, MD 20892 USA.
RP Ehler, M (reprint author), Univ Vienna, Fac Math, Vienna, Austria.
EM martin.ehler@univie.ac.at
RI Wong, Wai/B-6118-2017
OI Wong, Wai/0000-0003-0681-4016
FU National Institute of Child Health and Human Development/National
Institutes of Health; Research Career Transition Awards Program of
National Institutes of Health; German Science Foundation [EH
405/1-1/575910]; National Science Foundation [CBET 0854233]; Defense
Threat Reduction Agency [HDTRA 1-13-1-0015]; Vienna Science and
Technology Fund [VRG12-009]
FX This material is based upon work supported in part by intramural
research funds from the National Institute of Child Health and Human
Development/National Institutes of Health, the Research Career
Transition Awards Program of the National Institutes of Health and the
German Science Foundation under Grant EH 405/1-1/575910, the National
Science Foundation under Grant CBET 0854233, the Defense Threat
Reduction Agency under Grant HDTRA 1-13-1-0015, and the Vienna Science
and Technology Fund under Grant VRG12-009. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 69
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 JUL 21
PY 2015
VL 10
IS 7
AR e0131881
DI 10.1371/journal.pone.0131881
PG 22
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN6LZ
UT WOS:000358547600017
PM 26196397
ER
PT J
AU Yu, GQ
Fadrosh, D
Goedert, JJ
Ravel, J
Goldstein, AM
AF Yu, Guoqin
Fadrosh, Doug
Goedert, James J.
Ravel, Jacques
Goldstein, Alisa M.
TI Nested PCR Biases in Interpreting Microbial Community Structure in 16S
rRNA Gene Sequence Datasets
SO PLOS ONE
LA English
DT Article
ID TRACT
AB Background
Sequencing of the PCR-amplified 16S rRNA gene has become a common approach to microbial community investigations in the fields of human health and environmental sciences. This approach, however, is difficult when the amount of DNA is too low to be amplified by standard PCR. Nested PCR can be employed as it can amplify samples with DNA concentration several-fold lower than standard PCR. However, potential biases with nested PCRs that could affect measurement of community structure have received little attention.
Results
In this study, we used 17 DNAs extracted from vaginal swabs and 12 DNAs extracted from stool samples to study the influence of nested PCR amplification of the 16S rRNA gene on the estimation of microbial community structure using Illumina MiSeq sequencing. Nested and standard PCR methods were compared on alpha-and beta-diversity metrics and relative abundances of bacterial genera. The effects of number of cycles in the first round of PCR (10 vs. 20) and microbial diversity (relatively low in vagina vs. high in stool) were also investigated. Vaginal swab samples showed no significant difference in alpha diversity or community structure between nested PCR and standard PCR (one round of 40 cycles). Stool samples showed significant differences in alpha diversity (except Shannon's index) and relative abundance of 13 genera between nested PCR with 20 cycles in the first round and standard PCR (P<0.01), but not between nested PCR with 10 cycles in the first round and standard PCR. Operational taxonomic units (OTUs) that had low relative abundance (sum of relative abundance <0.167) accounted for most of the distortion (>27% of total OTUs in stool).
Conclusions
Nested PCR introduced bias in estimated diversity and community structure. The bias was more significant for communities with relatively higher diversity and when more cycles were applied in the first round of PCR. We conclude that nested PCR could be used when standard PCR does not work. However, rare taxa detected by nested PCR should be validated by other technologies.
C1 [Yu, Guoqin; Goedert, James J.; Goldstein, Alisa M.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Fadrosh, Doug; Ravel, Jacques] Univ Maryland, Sch Med, Inst Genom Sci, Baltimore, MD 21201 USA.
RP Yu, GQ (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
EM yug3@mail.nih.gov
OI Ravel, Jacques/0000-0002-0851-2233
FU Intramural Research Program of the NIH, National Cancer Institute
FX This study was supported by the Intramural Research Program of the NIH,
National Cancer Institute.
NR 20
TC 6
Z9 6
U1 2
U2 15
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 JUL 21
PY 2015
VL 10
IS 7
AR e0132253
DI 10.1371/journal.pone.0132253
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN6LZ
UT WOS:000358547600028
PM 26196512
ER
PT J
AU Liddell, AM
Davey, RT
Mehta, AK
Varkey, JB
Kraft, CS
Tseggay, GK
Badidi, O
Faust, AC
Brown, KV
Suffredini, AF
Barrett, K
Wolcott, MJ
Marconi, VC
Lyon, GM
Weinstein, GL
Weinmeister, K
Sutton, S
Hazbun, M
Albarino, CG
Reed, Z
Cannon, D
Stroher, U
Feldman, M
Ribner, BS
Lane, HC
Fauci, AS
Uyeki, TM
AF Liddell, Allison M.
Davey, Richard T., Jr.
Mehta, Aneesh K.
Varkey, Jay B.
Kraft, Colleen S.
Tseggay, Gebre K.
Badidi, Oghenetega
Faust, Andrew C.
Brown, Katia V.
Suffredini, Anthony F.
Barrett, Kevin
Wolcott, Mark J.
Marconi, Vincent C.
Lyon, G. Marshall, III
Weinstein, Gary L.
Weinmeister, Kenney
Sutton, Shelby
Hazbun, Munir
Albarino, Cesar G.
Reed, Zachary
Cannon, Debi
Stroeher, Ute
Feldman, Mark
Ribner, Bruce S.
Lane, H. Clifford
Fauci, Anthony S.
Uyeki, Timothy M.
TI Characteristics and Clinical Management of a Cluster of 3 Patients With
Ebola Virus Disease, Including the First Domestically Acquired Cases in
the United States
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID WEST-AFRICA; SIERRA-LEONE
AB Background: More than 26 000 cases of Ebola virus disease (EVD) have been reported in western Africa, with high mortality. Several patients have been medically evacuated to hospitals in the United States and Europe. Detailed clinical data are limited on the clinical course and management of patients with EVD outside western Africa.
Objective: To describe the clinical characteristics and management of a cluster of patients with EVD, including the first cases of Ebola virus (EBOV) infection acquired in the United States.
Design: Retrospective clinical case series.
Setting: Three U.S. hospitals in September and October 2014.
Patients: First imported EVD case identified in the United States and 2 secondary EVD cases acquired in the United States in critical care nurses who cared for the index case patient.
Measurements: Clinical recovery, EBOV RNA level, resolution of Ebola viremia, survival with discharge from hospital, or death.
Results: The index patient had high EBOV RNA levels, developed respiratory and renal failure requiring critical care support, and died. Both patients with secondary EBOV infection had nonspecific signs and symptoms and developed moderate illness; EBOV RNA levels were moderate, and both patients recovered.
Limitation: Both surviving patients received uncontrolled treatment with multiple investigational agents, including convalescent plasma, which limits generalizability of the results.
Conclusion: Early diagnosis, prompt initiation of supportive medical care, and moderate clinical illness likely contributed to successful outcomes in both survivors. The inability to determine the potential benefit of investigational therapies and the effect of patient-specific factors that may have contributed to less severe illness highlight the need for controlled clinical studies of these interventions, especially in the setting of a high level of supportive medical care.
C1 [Liddell, Allison M.] Texas Hlth Presbyterian Hosp Dallas, Dallas, TX 75231 USA.
NIH, Ctr Clin, Bethesda, MD 20892 USA.
Emory Univ, Sch Med, Atlanta, GA USA.
Ctr Dis Control & Prevent, Atlanta, GA USA.
US Army, Med Res Inst Infect Dis, Frederick, MD USA.
RP Liddell, AM (reprint author), Texas Hlth Presbyterian Hosp Dallas, 8230 Walnut Hill Lane,Suite 308, Dallas, TX 75231 USA.
EM allisonliddell@texashealth.org
RI Mehta, Aneesh/B-8054-2012; Marconi, Vincent/N-3210-2014
OI Mehta, Aneesh/0000-0002-6552-9162; Marconi, Vincent/0000-0001-8409-4689
FU National Center for Advancing Translational Sciences of the National
Institutes of Health [Atlanta Clinical and Translational Science
Institute] [UL1TR000454]
FX The authors thank the entire staff of Texas Health Presbyterian Hospital
Dallas, particularly Edward Goodman, MD, Beverly Dickson, MD, Otto
Javier Marquez-Kerguelen, MD, Sarah S. Way, MD, Mark Till, MD, Glen
Owen, MD, Bruce Wall, MD, Elaine Whitaker, MD, David Gonzales, MD, and
Sarita Sharma-Louys, MD; Texas Health Resources for its unwavering
support; William Dorman and Samantha Tostenson of the U.S. Army Medical
Research Institute of Infectious Diseases for technical work on RT-PCR
assays; David Henderson, MD, and Tara Palmore, MD, of the National
Institutes of Health Clinical Center for their infection control
leadership; the nursing and hospital epidemiology staff at the National
Institutes of Health Clinical Center for their outstanding patient care;
Anne Winkler, MD, of the Emory University Hospital Serious Communicable
Diseases Unit for coordinating the convalescent plasma collection and
administration; all of the members of the Emory University Hospital
Serious Communicable Diseases Unit team for their outstanding
contributions to the patient's excellent care (supported by award
UL1TR000454 from the National Center for Advancing Translational
Sciences of the National Institutes of Health [Atlanta Clinical and
Translational Science Institute]); and Tara Sealy, MS, Aridith Gibbons,
and Bobbie Rae Erickson, MPH, of the Centers for Disease Control and
Prevention for their technical support on the laboratory assays.
NR 19
TC 40
Z9 41
U1 2
U2 9
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD JUL 21
PY 2015
VL 163
IS 2
BP 81
EP +
DI 10.7326/M15-0530
PG 14
WC Medicine, General & Internal
SC General & Internal Medicine
GA CN4NS
UT WOS:000358407500015
PM 25961438
ER
PT J
AU Morris, SA
Gaheen, S
Lijowski, M
Heiskanen, M
Klemm, J
AF Morris, Stephanie A.
Gaheen, Sharon
Lijowski, Michal
Heiskanen, Mervi
Klemm, Juli
TI Experiences in supporting the structured collection of cancer
nanotechnology data using caNanoLab
SO BEILSTEIN JOURNAL OF NANOTECHNOLOGY
LA English
DT Article
DE caNanoLab; cancer research; databases; nanomaterials; nanomedicine
ID NANOMEDICINE
AB The cancer Nanotechnology Laboratory (caNanoLab) data portal is an online nanomaterial database that allows users to submit and retrieve information on well-characterized nanomaterials, including composition, in vitro and in vivo experimental characterizations, experimental protocols, and related publications. Initiated in 2006, caNanoLab serves as an established resource with an infrastructure supporting the structured collection of nanotechnology data to address the needs of the cancer biomedical and nanotechnology communities. The portal contains over 1,000 curated nanomaterial data records that are publicly accessible for review, comparison, and re-use, with the ultimate goal of accelerating the translation of nanotechnology-based cancer therapeutics, diagnostics, and imaging agents to the clinic. In this paper, we will discuss challenges associated with developing a nanomaterial database and recognized needs for nanotechnology data curation and sharing in the biomedical research community. We will also describe the latest version of caNanoLab, caNanoLab 2.0, which includes enhancements and new features to improve usability such as personalized views of data and enhanced search and navigation.
C1 [Morris, Stephanie A.] NCI, Off Canc Nanotechnol Res, NIH, Bethesda, MD 20892 USA.
[Gaheen, Sharon] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA.
[Lijowski, Michal] Essential Software Inc, Potomac, MD 20854 USA.
[Heiskanen, Mervi; Klemm, Juli] NCI, Ctr Biomed Informat & Informat Technol, NIH, Rockville, MD 20850 USA.
RP Morris, SA (reprint author), NCI, Off Canc Nanotechnol Res, NIH, 31 Ctr Dr, Bethesda, MD 20892 USA.
EM morriss2@mail.nih.gov
FU Federal funds from the National Cancer Institute, National Institutes of
Health [HHSN261200800001E]
FX The caNanoLab project has been funded in whole or in part with Federal
funds from the National Cancer Institute, National Institutes of Health,
under Contract No. HHSN261200800001E. The content of this publication
does not necessarily reflect the views or policies of the Department of
Health and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government.
NR 23
TC 4
Z9 4
U1 2
U2 3
PU BEILSTEIN-INSTITUT
PI FRANKFURT AM MAIN
PA TRAKEHNER STRASSE 7-9, FRANKFURT AM MAIN, 60487, GERMANY
SN 2190-4286
J9 BEILSTEIN J NANOTECH
JI Beilstein J. Nanotechnol.
PD JUL 21
PY 2015
VL 6
BP 1580
EP 1593
DI 10.3762/bjnano.6.161
PG 14
WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary;
Physics, Applied
SC Science & Technology - Other Topics; Materials Science; Physics
GA CN2UE
UT WOS:000358276600001
PM 26425409
ER
PT J
AU Peercy, BE
Sherman, AS
Bertram, R
AF Peercy, Bradford E.
Sherman, Arthur S.
Bertram, Richard
TI Modeling of Glucose-Induced cAMP Oscillations in Pancreatic beta Cells:
cAMP Rocks when Metabolism Rolls
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID PROTEIN-COUPLED RECEPTORS; INSULIN-SECRETION; ADENYLATE-CYCLASE;
CYTOPLASMIC CA2+; CYCLIC-AMP; COMPUTATIONAL APPROACH; REGULATED
EXOCYTOSIS; ELECTRICAL-ACTIVITY; MOUSE ISLETS; K+ CHANNELS
AB Recent advances in imaging technology have revealed oscillations of cyclic adenosine monophosphate (cAMP) in insulin-secreting cells. These oscillations may be in phase with cytosolic calcium oscillations or out of phase. cAMP oscillations have previously been modeled as driven by oscillations in calcium, based on the known dependence of the enzymes that generate cAMP (adenylyl cyclase) and degrade it (phosphodiesterase). However, cAMP oscillations have also been reported to occur in the absence of calcium oscillations. Motivated by similarities between the properties of cAMP and metabolic oscillations in pancreatic beta cells, we propose here that in addition to direct control by calcium, cAMP is controlled by metabolism. Specifically, we hypothesize that AMP inhibits adenylyl cyclase. We incorporate this hypothesis into the dual oscillator model for beta cells, in which metabolic (glycolytic) oscillations cooperate with modulation of ion channels and metabolism by calcium. We show that the combination of oscillations in AMP and calcium in the dual oscillator model can account for the diverse oscillatory patterns that have been observed, as well as for experimental perturbations of those patterns. Predictions to further test the model are provided.
C1 [Peercy, Bradford E.] Univ Maryland, Dept Math & Stat, Baltimore, MD 21201 USA.
[Sherman, Arthur S.] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
[Bertram, Richard] Florida State Univ, Dept Math & Programs Neurosci & Mol Biophys, Tallahassee, FL 32306 USA.
RP Sherman, AS (reprint author), NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
EM asherman@nih.gov
FU Intramural Research Program of the National Institutes of Health;
National Institute of Diabetes and Digestive and Kidney Diseases;
National Science Foundation [DMS-0917664]
FX A.S. was supported by the Intramural Research Program of the National
Institutes of Health, National Institute of Diabetes and Digestive and
Kidney Diseases. R.B. was supported by National Science Foundation grant
DMS-0917664.
NR 49
TC 1
Z9 1
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 JUL 21
PY 2015
VL 109
IS 2
BP 439
EP 449
DI 10.1016/j.bpj.2015.06.024
PG 11
WC Biophysics
SC Biophysics
GA CN3GE
UT WOS:000358312800028
PM 26200880
ER
PT J
AU Manoussaki, D
Shin, WD
Waterman, CM
Chadwick, RS
AF Manoussaki, Daphne
Shin, William D.
Waterman, Clare M.
Chadwick, Richard S.
TI Cytosolic pressure provides a propulsive force comparable to actin
polymerization during lamellipod protrusion
SO SCIENTIFIC REPORTS
LA English
DT Article
ID CELLS; NETWORKS; ORGANIZATION; MICROTUBULES; FILOPODIA; FILAMENTS
AB Does cytosolic pressure facilitate f-actin polymerization to push the leading edge of a cell forward during self-propelled motion? AFM force-distance (f-d) curves obtained from lamellipodia of live cells often exhibit a signal from which the tension, bending modulus, elastic modulus and thickness in the membrane-cortex complex can be estimated close to the contact point. These measurements permit an estimate of the cytosolic pressure via the canonical Laplace force balance. The deeper portion of the f-d curve allows estimation of the bulk modulus of the cytoskeleton after removal of the bottom effect artifact. These estimates of tension, pressure, cortex thickness and elastic moduli imply that cytosolic pressure both pushes the membrane forward and compresses the actin cortex rearward to facilitate f-actin polymerization. We also estimate that cytosolic pressure fluctuations, most likely induced by myosin, provide a propulsive force comparable to that provided by f-actin polymerization in a lamellipod.
C1 [Manoussaki, Daphne] Tech Univ Crete, Sch Elect & Comp Engn, Hania, Greece.
[Shin, William D.; Waterman, Clare M.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA.
[Chadwick, Richard S.] NIDCD, Lab Cellular Biol, Sect Auditory Mech, NIH, Bethesda, MD 20892 USA.
RP Chadwick, RS (reprint author), NIDCD, Lab Cellular Biol, Sect Auditory Mech, NIH, Bethesda, MD 20892 USA.
EM chadwick@nidcd.nih.gov
OI Waterman, Clare/0000-0001-6142-6775
FU NIH Intramural Director's Challenge Innovation Award
FX The authors would like to thank Nikon Instruments for the loan of the
spinning disk confocal and Agilent laser launch and the support of these
instruments under the "Nikon Partners in Research Program". The authors
also thank Bruker for a loan of the AFM baseplate and a trial license of
MIRO software. This work was supported by an NIH Intramural Director's
Challenge Innovation Award to R.S.C and C.M.W.
NR 26
TC 1
Z9 1
U1 2
U2 10
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 JUL 21
PY 2015
VL 5
AR 12314
DI 10.1038/srep12314
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN2IT
UT WOS:000358245000001
PM 26197304
ER
PT J
AU Libich, DS
Tugarinov, V
Clore, GM
AF Libich, David S.
Tugarinov, Vitali
Clore, G. Marius
TI Intrinsic unfoldase/foldase activity of the chaperonin GroEL directly
demonstrated using multinuclear relaxation-based NMR
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE chaperonins; invisible states; dark state exchange saturation transfer;
lifetime line broadening; relaxation dispersion
ID ATOMIC-RESOLUTION DYNAMICS; MOLECULAR CHAPERONES; DISPERSION
EXPERIMENTS; CONFORMATIONAL STATES; DARK-STATE; SH3 DOMAIN; PROTEINS;
SPECTROSCOPY; EXCHANGE; MECHANISM
AB The prototypical chaperonin GroEL assists protein folding through an ATP-dependent encapsulation mechanism. The details of how GroEL folds proteins remain elusive, particularly because encapsulation is not an absolute requirement for successful re/folding. Here we make use of a metastable model protein substrate, comprising a triple mutant of Fyn SH3, to directly demonstrate, by simultaneous analysis of three complementary NMR-based relaxation experiments (lifetime line broadening, dark state exchange saturation transfer, and Carr-Purcell-Meinboom-Gill relaxation dispersion), that apo GroEL accelerates the overall interconversion rate between the native state and a well-defined folding intermediate by about 20-fold, under conditions where the "invisible" GroEL-bound states have occupancies below 1%. This is largely achieved through a 500-fold acceleration in the folded-to-intermediate transition of the protein substrate. Catalysis is modulated by a kinetic deuterium isotope effect that reduces the overall interconversion rate between the GroEL-bound species by about 3-fold, indicative of a significant hydrophobic contribution. The location of the GroEL binding site on the folding intermediate, mapped from N-15, H-1(N), and C-13(methyl) relaxation dispersion experiments, is composed of a prominent, surface-exposed hydrophobic patch.
C1 [Libich, David S.; Tugarinov, Vitali; Clore, G. Marius] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Clore, GM (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM mariusc@mail.nih.gov
FU National Institute of Diabetes and Digestive and Kidney
Diseases/National Institutes of Health (NIDDK/NIH); AIDS Targeted
Antiviral Program of the NIH
FX We thank G. H. Lorimer and A. Szabo for insightful discussions, G. H.
Lorimer for the GroEL and Rubisco clones, and L. E. Kay for the original
Fyn SH3 clones. This work was supported by the intramural program of the
National Institute of Diabetes and Digestive and Kidney
Diseases/National Institutes of Health (NIDDK/NIH) and the AIDS Targeted
Antiviral Program of the NIH Director (G.M.C.).
NR 50
TC 13
Z9 13
U1 0
U2 17
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 21
PY 2015
VL 112
IS 29
BP 8817
EP 8823
DI 10.1073/pnas.1510083112
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN2BJ
UT WOS:000358225100037
PM 26124125
ER
PT J
AU Coghill, AE
Shiels, MS
Suneja, G
Engels, EA
AF Coghill, Anna E.
Shiels, Meredith S.
Suneja, Gita
Engels, Eric A.
TI Elevated Cancer-Specific Mortality Among HIV-Infected Patients in the
United States
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID COMBINATION ANTIRETROVIRAL THERAPY; AIDS-DEFINING MALIGNANCIES;
FIBROBLAST-GROWTH-FACTOR; NON-HODGKIN-LYMPHOMA; T-CELLS;
COLORECTAL-CANCER; KAPOSIS-SARCOMA; TAT PROTEIN; IMMUNODEFICIENCY;
SURVIVAL
AB Purpose
Despite advances in the treatment of HIV, HIV-infected people remain at increased risk for many cancers, and the number of non-AIDS-defining cancers is increasing with the aging of the HIV-infected population. No prior study has comprehensively evaluated the effect of HIV on cancer-specific mortality.
Patients and Methods
We identified cases of 14 common cancers occurring from 1996 to 2010 in six US states participating in a linkage of cancer and HIV/AIDS registries. We used Cox regression to examine the association between patient HIV status and death resulting from the presenting cancer (ascertained from death certificates), adjusting for age, sex, race/ethnicity, year of cancer diagnosis, and cancer stage. We included 1,816,461 patients with cancer, 6,459 (0.36%) of whom were HIV infected.
Results
Cancer-specific mortality was significantly elevated in HIV-infected compared with HIV-uninfected patients for many cancers: colorectum (adjusted hazard ratio [HR], 1.49; 95% CI, 1.21 to 1.84), pancreas (HR, 1.71; 95% CI, 1.35 to 2.18), larynx (HR, 1.62; 95% CI, 1.06 to 2.47), lung (HR, 1.28; 95% CI, 1.17 to 1.39), melanoma (HR, 1.72; 95% CI, 1.09 to 2.70), breast (HR, 2.61; 95% CI, 2.06 to 3.31), and prostate (HR, 1.57; 95% CI, 1.02 to 2.41). HIV was not associated with increased cancer-specific mortality for anal cancer, Hodgkin lymphoma, or diffuse large B-cell lymphoma. After further adjustment for cancer treatment, HIV remained associated with elevated cancer-specific mortality for common non-AIDS-defining cancers: colorectum (HR, 1.40; 95% CI, 1.09 to 1.80), lung (HR, 1.28; 95% CI, 1.14 to 1.44), melanoma (HR, 1.93; 95% CI, 1.14 to 3.27), and breast (HR, 2.64; 95% CI, 1.86 to 3.73).
Conclusion
HIV-infected patients with cancer experienced higher cancer-specific mortality than HIV-uninfected patients, independent of cancer stage or receipt of cancer treatment. The elevation in cancer-specific mortality among HIV-infected patients may be attributable to unmeasured stage or treatment differences as well as a direct relationship between immunosuppression and tumor progression. (C) 2015 by American Society of Clinical Oncology
C1 [Coghill, Anna E.; Shiels, Meredith S.; Engels, Eric A.] NCI, Rockville, MD 20892 USA.
[Suneja, Gita] Univ Utah, Sch Med, Salt Lake City, UT USA.
RP Coghill, AE (reprint author), NCI, 9609 Med Ctr Dr, Rockville, MD 20892 USA.
EM anna.coghill@nih.gov
FU Intramural Research Program of the National Cancer Institute (NCI); NCI
SEER program: Connecticut [HHSN261201000024C]; NCI SEER program: New
Jersey [HHSN261201300021I, N01-PC-2013-00021]; National Program of
Cancer Registries of the Centers for Disease Control and Prevention
(CDC): Colorado [U58DP000848-04]; National Program of Cancer Registries
of the Centers for Disease Control and Prevention (CDC): Georgia
[5U58DP00387501]; National Program of Cancer Registries of the Centers
for Disease Control and Prevention (CDC): Michigan [5U58DP000812-03];
National Program of Cancer Registries of the Centers for Disease Control
and Prevention (CDC): New Jersey [5U58/DP003931-02]; National Program of
Cancer Registries of the Centers for Disease Control and Prevention
(CDC): Texas [5U58DP000824-04]; state of New Jersey; CDC HIV Incidence
and Case Surveillance Branch, National HIV Surveillance Systems:
Colorado [5U62PS001005-05]; CDC HIV Incidence and Case Surveillance
Branch, National HIV Surveillance Systems: Connecticut
[5U62PS001005-05]; CDC HIV Incidence and Case Surveillance Branch,
National HIV Surveillance Systems: Michigan [U62PS004011-02]; CDC HIV
Incidence and Case Surveillance Branch, National HIV Surveillance
Systems: New Jersey [U62PS004001-2]
FX Supported in part by the Intramural Research Program of the National
Cancer Institute (NCI). The following cancer registries were supported
by the NCI SEER program: Connecticut (Grant No. HHSN261201000024C) and
New Jersey (Grants No. HHSN261201300021I and N01-PC-2013-00021). The
following cancer registries were supported by the National Program of
Cancer Registries of the Centers for Disease Control and Prevention
(CDC): Colorado (Grant No. U58DP000848-04), Georgia (Grant No.
5U58DP00387501), Michigan (Grant No. 5U58DP000812-03), New Jersey (Grant
No. 5U58/DP003931-02), and Texas (Grant No. 5U58DP000824-04). The New
Jersey State Cancer Registry was also supported by the state of New
Jersey. The following HIV registries were supported by CDC HIV Incidence
and Case Surveillance Branch, National HIV Surveillance Systems:
Colorado and Connecticut (Grant No. 5U62PS001005-05), Michigan (Grant
No. U62PS004011-02), and New Jersey (Grant No. U62PS004001-2).
NR 41
TC 33
Z9 35
U1 0
U2 4
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 JUL 20
PY 2015
VL 33
IS 21
BP 2376
EP U77
DI 10.1200/JCO.2014.59.5967
PG 11
WC Oncology
SC Oncology
GA CR9DR
UT WOS:000361653900009
PM 26077242
ER
PT J
AU Sadowski, SM
Boufraqech, M
Zhang, LS
Mehta, A
Kapur, P
Zhang, YQ
Li, ZY
Shen, M
Kebebew, E
AF Sadowski, Samira M.
Boufraqech, Myriem
Zhang, Lisa
Mehta, Amit
Kapur, Payal
Zhang, Yaqin
Li, Zhuyin
Shen, Min
Kebebew, Electron
TI Torin2 targets dysregulated pathways in anaplastic thyroid cancer and
inhibits tumor growth and metastasis
SO ONCOTARGET
LA English
DT Article
DE torin2; mTORC1 inhibitor; mTOR; anaplastic thyroid cancer; quantitative
high-troughput screening
ID SIGNALING PATHWAYS; MOUSE MODEL; CARCINOMA; MTOR; ACTIVATION; AKT;
EXPRESSION; RESISTANCE; MECHANISM; APOPTOSIS
AB Anaplastic thyroid cancer (ATC) is rare but it is one of the most lethal human malignancies with no effective therapy. There is a pressing need to identify new therapeutic agents for ATC. We performed quantitative high-throughput screening (qHTS) in ATC cell lines using a compound library of 3,282 drugs. qHTS identified 100 pan-active agents. Enrichment analysis of qHTS data showed drugs targeting mTOR were one of the most active drug categories, and Torin2 showed the highest efficacy. We found mTOR to be upregulated in ATC. Treatment of multiple ATC cell lines with Torin2 showed significant dose-dependent inhibition of cellular proliferation with caspase-dependent apoptosis and G1/S phase arrest. Torin2 inhibited cellular migration and inhibited the phosphorylation of key effectors of the mTOR-pathway (AKT, 4E-BP1 and 70S6K), as well as claspin and survivin expression, regulators of cell cycle and apoptosis. In our in vivo mouse model of metastatic ATC, Torin2 inhibited tumor growth and metastasis and significantly prolonged overall survival. Our findings suggest that Torin2 is a promising agent for ATC therapy and that it effectively targets upregulated pathways in human ATC.
C1 [Sadowski, Samira M.; Boufraqech, Myriem; Zhang, Lisa; Kebebew, Electron] NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Mehta, Amit] Geisel Sch Med Dartmouth, Hanover, NH USA.
[Kapur, Payal] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA.
[Zhang, Yaqin; Li, Zhuyin; Shen, Min] NIH, Div Discovery Innovat, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
RP Sadowski, SM (reprint author), NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA.
EM samira.sadowskiveuthey@nih.gov
RI Boufraqech, Myriem/E-4823-2016
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 46
TC 4
Z9 5
U1 0
U2 1
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD JUL 20
PY 2015
VL 6
IS 20
BP 18038
EP 18049
PG 12
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA CO2VL
UT WOS:000359014700024
PM 25945839
ER
PT J
AU Hartley, SW
Mullikin, JC
AF Hartley, Stephen W.
Mullikin, James C.
TI QoRTs: a comprehensive toolset for quality control and data processing
of RNA-Seq experiments
SO BMC BIOINFORMATICS
LA English
DT Article
DE Quality Control; RNA-Seq; Next-generation sequencing; Differential
expression; Differential transcript regulation; Differential splicing
ID DNA-SEQUENCE DIFFERENCES; DIFFERENTIAL EXPRESSION ANALYSIS; INTEGRATIVE
GENOMICS VIEWER; HUMAN TRANSCRIPTOME; WIDESPREAD RNA; NORMALIZATION
AB Background: High-throughput next-generation RNA sequencing has matured into a viable and powerful method for detecting variations in transcript expression and regulation. Proactive quality control is of critical importance as unanticipated biases, artifacts, or errors can potentially drive false associations and lead to flawed results.
Results: We have developed the Quality of RNA-Seq Toolset, or QoRTs, a comprehensive, multifunction toolset that assists in quality control and data processing of high-throughput RNA sequencing data.
Conclusions: QoRTs generates an unmatched variety of quality control metrics, and can provide cross-comparisons of replicates contrasted by batch, biological sample, or experimental condition, revealing any outliers and/or systematic issues that could drive false associations or otherwise compromise downstream analyses. In addition, QoRTs simultaneously replaces the functionality of numerous other data-processing tools, and can quickly and efficiently generate quality control metrics, coverage counts (for genes, exons, and known/novel splice-junctions), and browser tracks. These functions can all be carried out as part of a single unified data-processing/quality control run, greatly reducing both the complexity and the total runtime of the analysis pipeline. The software, source code, and documentation are available online at http://hartleys.github.io/QoRTs.
C1 [Hartley, Stephen W.; Mullikin, James C.] NHGRI, Comparat Genom Anal Unit, Canc Genet & Comparat Genom Branch, NIH, Bethesda, MD 20892 USA.
RP Hartley, SW (reprint author), NHGRI, Comparat Genom Anal Unit, Canc Genet & Comparat Genom Branch, NIH, Bethesda, MD 20892 USA.
EM stephen.hartley@nih.gov
FU Intramural NIH HHS
NR 31
TC 9
Z9 9
U1 0
U2 12
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 JUL 19
PY 2015
VL 16
AR 224
DI 10.1186/s12859-015-0670-5
PG 7
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA CM9LX
UT WOS:000358031000001
PM 26187896
ER
PT J
AU Song, MS
AF Song, Minsun
TI Jackknife-based gene-gene interaction tests for untyped SNPs
SO BMC GENETICS
LA English
DT Article
DE Jackknife-based testing framework; Untyped SNP; Imputation-based
testing; Gene-gene interaction
ID GENOME-WIDE ASSOCIATION; LUNG-CANCER; SUSCEPTIBILITY LOCUS; GENOTYPE
DATA; REGRESSION; DISEASES; MODEL; TUNA; MAP
AB Background: Testing gene-gene interaction in genome-wide association studies generally yields lower power than testing marginal association. Meta-analysis that combines different genotyping platforms is one method used to increase power when assessing gene-gene interactions, which requires a test for interaction on untyped SNPs. However, to date, formal statistical tests for gene-gene interaction on untyped SNPs have not been thoroughly addressed. The key concern for gene-gene interaction testing on untyped SNPs located on different chromosomes is that the pair of genes might not be independent and the current generation of imputation methods provides imputed genotypes at the marginal accuracy.
Results: In this study we address this challenge and describe a novel method for testing gene-gene interaction on marginally imputed values of untyped SNPs. We show that our novel Wald-type test statistics for interactions with and without constraints in the interaction parameters follow the asymptotic distributions which are the same as those of the corresponding tests for typed SNPs. Through simulations, we show that the proposed tests properly control type I error and are more powerful than the extension of the classical dosage method to interaction tests. The increase in power results from a proper correction for the uncertainty in imputation through the variance estimator using the jackknife, one of resampling techniques. We apply the method to detect interactions between SNPs on chromosomes 5 and 15 on lung cancer data. The inclusion of the results at the untyped SNPs provides a much more detailed information at the regions of interest.
Conclusions: As demonstrated by the simulation studies and real data analysis, our approaches outperform the application of traditional dosage method to detection of gene-gene interaction in terms of power while providing control of the type I error.
C1 NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
RP Song, MS (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr, Rockville, MD 20852 USA.
EM songm4@mail.nih.gov
NR 30
TC 0
Z9 0
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2156
J9 BMC GENET
JI BMC Genet.
PD JUL 18
PY 2015
VL 16
DI 10.1186/s12863-015-0225-9
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA CM9MU
UT WOS:000358033400001
ER
PT J
AU Oakley, RH
Cruz-Topete, D
Foley, JF
Myers, PH
Chambon, P
Willis, MS
Cidlowski, JA
AF Oakley, Robert H.
Cruz-Topete, Diana
Foley, Julie F.
Myers, Page H.
Chambon, Pierre
Willis, Monte S.
Cidlowski, John A.
TI Genetic Deletion of Cardiomyocyte Mineralocorticoid Receptors Prevents
Cardiac Dysfunction and Premature Death in Mice Lacking Glucocorticoid
Receptors in the Heart
SO CIRCULATION RESEARCH
LA English
DT Meeting Abstract
CT American-Stroke-Association/American-Heart-Association Basic
Cardiovascular Sciences Scientific Sessions - Pathways to Cardiovascular
Therapeutics
CY JUL 13-16, 2015
CL New Orleans, LA
SP Amer Stroke Assoc, Amer Heart Assoc, Council Basic Cardiovascular Sci
DE glucocorticoid receptor; mineralocorticoid receptor; transgenic mice
C1 [Oakley, Robert H.; Cruz-Topete, Diana; Foley, Julie F.; Myers, Page H.; Cidlowski, John A.] NIEHS, NIH, Rsch Triangle Pk, NC USA.
[Chambon, Pierre] Inst Genet & Mol & Cellular Biol, Strasbourg, France.
[Willis, Monte S.] Univ N Carolina, McAllister Heart Inst, Chapel Hill, NC USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7330
EI 1524-4571
J9 CIRC RES
JI Circ.Res.
PD JUL 17
PY 2015
VL 117
SU 1
MA 216
PG 1
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA DJ9SI
UT WOS:000374552800189
ER
PT J
AU Green, SA
Smith, M
Hasley, RB
Stephany, D
Harned, A
Nagashima, K
Abdullah, S
Pittaluga, S
Imamichi, T
Qin, J
Rupert, A
Ober, A
Lane, HC
Catalfamo, M
AF Green, Samantha A.
Smith, Mindy
Hasley, Rebecca B.
Stephany, David
Harned, Adam
Nagashima, Kunio
Abdullah, Shahed
Pittaluga, Stefania
Imamichi, Tomozumi
Qin, Jing
Rupert, Adam
Ober, Alex
Lane, H. Clifford
Catalfamo, Marta
TI Activated platelet-T-cell conjugates in peripheral blood of patients
with HIV infection: coupling coagulation/inflammation and T cells
SO AIDS
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; ACUTE MYOCARDIAL-INFARCTION/; TISSUE
FACTOR EXPRESSION; P-SELECTIN; IMMUNE ACTIVATION; MEMBRANE
MICROPARTICLES; COAGULATION BIOMARKERS; CIRCULATING MONOCYTES;
RHEUMATOID-ARTHRITIS; DISEASE PROGRESSION
AB Background:
Despite successfully suppressed viremia by treatment, patients with high levels of biomarkers of coagulation/inflammation are at an increased risk of developing non-AIDS defining serious illnesses such as cardiovascular diseases. Thus, there is a relationship between persistent immune activation and coagulation/inflammation, although the mechanisms are poorly understood. Platelets play an important role in this process. Although interactions between platelets and elements of the innate immune system, such as monocytes, are well described, little is known about the interaction between platelets and the adaptive immune system.
Design:
We investigated the interaction of a component of the coagulation system, platelets, and the adaptive immune system T cells.
Methods:
Healthy controls and combination antiretroviral therapy (cART)-treated HIV-infected patients with viral loads of less than 40 copies/ml for more than 15 months were analysed for platelet-T-cell conjugate formation.
Results:
Platelets can form conjugates with T cells and were preferentially seen in CD4(+) and CD8(+) T-cell subsets with more differentiated phenotypes [memory, memory/effector and terminal effector memory (TEM)]. Compared with healthy controls, these conjugates in patients with HIV infection were more frequent, more often composed of activated platelets (CD42b(+)CD62P(+)), and were significantly associated with the D-dimer serum levels.
Conclusion:
These data support a model in which platelet-T-cell conjugates may play a critical role in the fast recruitment of antigen-experienced T cells to the place of injury. This mechanism can contribute in maintaining a state of coagulation/inflammation observed in these patients contributing to the pathology of the disease.
C1 [Green, Samantha A.; Smith, Mindy; Hasley, Rebecca B.; Ober, Alex; Lane, H. Clifford; Catalfamo, Marta] NIAID, CMRS Lab Immunoregulat, NIH, Bethesda, MD 20892 USA.
[Stephany, David] NIAID, Res Technol Branch, NIH, Bethesda, MD 20892 USA.
[Harned, Adam; Nagashima, Kunio] Leidos Biomed Res Inc, Electron Microscope Lab, Canc Res Technol Program, Frederick, MD USA.
[Imamichi, Tomozumi] Leidos Biomed Res Inc, Lab Human Retrovirol, Frederick, MD USA.
[Abdullah, Shahed; Pittaluga, Stefania] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Qin, Jing] NIAID, Biostat Res Branch, DCR, NIH, Bethesda, MD 20892 USA.
[Rupert, Adam] Leidos Biomed Res Inc, AIDS Monitoring Lab, Frederick, MD USA.
RP Catalfamo, M (reprint author), NIAID, CMRS Lab Immunoregulat, NIH, Bldg 10 Room 11B07,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM catalfam@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; National Institute of Allergy and Infectious
Disease
FX Leidos Biomedical Research Inc has been funded in whole or in part with
federal funds from the National Cancer Institute, National Institutes of
Health, under Contract No. HHSN261200800001E. The content of this
publication does not necessarily reflect the views or policies of the
Department of Health and Human Services, nor does mention of trade
names, commercial products or organizations imply endorsement by the
U.S. Government. This research was supported [in part] by the National
Institute of Allergy and Infectious Disease.
NR 44
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U1 2
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0269-9370
EI 1473-5571
J9 AIDS
JI Aids
PD JUL 17
PY 2015
VL 29
IS 11
BP 1297
EP 1308
DI 10.1097/QAD.0000000000000701
PG 12
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA CR1UV
UT WOS:000361111500002
PM 26002800
ER
PT J
AU Chattopadhyay, MK
Keembiyehetty, CN
Chen, WP
Tabor, H
AF Chattopadhyay, Manas K.
Keembiyehetty, Chithra N.
Chen, Weiping
Tabor, Herbert
TI Polyamines Stimulate the Level of the sigma(38) Subunit (RpoS) of
Escherichia coli RNA Polymerase, Resulting in the Induction of the
Glutamate Decarboxylase-dependent Acid Response System via the gadE
Regulon
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID STATIONARY-PHASE; GENE-EXPRESSION; SHIGELLA-FLEXNERI; RESISTANCE;
STRESS; PROTEIN; MECHANISMS; GROWTH; PPGPP; CELLS
AB To study the physiological roles of polyamines, we carried out a global microarray analysis on the effect of adding polyamines to an Escherichia coli mutant that lacks polyamines because of deletions in the genes in the polyamine biosynthetic pathway. Previously, we have reported that the earliest response to polyamine addition is the increased expression of the genes for the glutamate-dependent acid resistance system (GDAR). We also presented preliminary evidence for the involvement of rpoS and gadE regulators. In the current study, further confirmation of the regulatory roles of rpoS and gadE is shown by a comparison of genome-wide expression profiling data from a series of microarrays comparing the genes induced by polyamine addition to polyamine-free rpoS(+)/gadE(+) cells with genes induced by polyamine addition to polyamine-free Delta rpoS/gadE(+) and rpoS6+/Delta gadE cells. The results indicate that most of the genes in the E. coli GDAR system that are induced by polyamines require rpoS and gadE. Our data also show that gadE is the main regulator of GDAR and other acid fitness island genes. Both polyamines and rpoS are necessary for the expression of gadE gene from the three promoters of gadE (P1, P2, and P3). The most important effect of polyamine addition is the very rapid increase in the level of RpoS sigma factor. Our current hypothesis is that polyamines increase the level of RpoS protein and that this increased RpoS level is responsible for the stimulation of gadE expression, which in turn induces the GDAR system in E. coli.
C1 [Chattopadhyay, Manas K.; Tabor, Herbert] NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA.
[Keembiyehetty, Chithra N.; Chen, Weiping] NIDDK, Genom Core Facil, NIH, Bethesda, MD 20892 USA.
RP Chattopadhyay, MK (reprint author), NIDDK, NIH, 8 Ctr Dr,Bldg 8,Rm 219, Bethesda, MD 20892 USA.
EM manasc@intra.niddk.nih.gov
FU National Institutes of Health NIDDK Intramural Research Program
FX This work was supported, in whole or in part, by National Institutes of
Health NIDDK Intramural Research Program. The authors declare that they
have no conflicts of interest with the contents of this article.
NR 56
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U1 0
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 17
PY 2015
VL 290
IS 29
BP 17809
EP 17821
DI 10.1074/jbc.M115.655688
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CN5ZB
UT WOS:000358511700018
PM 26025365
ER
PT J
AU Ping, PP
Gustafsson, AB
Bers, DM
Blatter, LA
Cai, H
Jahangir, A
Kelly, D
Muoio, D
O'Rourke, B
Rabinovitch, P
Trayanova, N
Van Eyk, J
Weiss, JN
Wong, R
Longacre, LS
AF Ping, Peipei
Gustafsson, Asa B.
Bers, Don M.
Blatter, Lothar A.
Cai, Hua
Jahangir, Arshad
Kelly, Daniel
Muoio, Deborah
O'Rourke, Brian
Rabinovitch, Peter
Trayanova, Natalia
Van Eyk, Jennifer
Weiss, James N.
Wong, Renee
Longacre, Lisa Schwartz
TI Harnessing the Power of Integrated Mitochondrial Biology and Physiology
A Special Report on the NHLBI Mitochondria in Heart Diseases Initiative
SO CIRCULATION RESEARCH
LA English
DT Article
DE cardiovascular disease; cell death; heart diseases; mitochondria;
National Heart, Lung, and Blood Institute ( U. S.)
ID FAILURE
AB Mitochondrial biology is the sum of diverse phenomena from molecular profiles to physiological functions. A mechanistic understanding of mitochondria in disease development, and hence the future prospect of clinical translations, relies on a systems-level integration of expertise from multiple fields of investigation. Upon the successful conclusion of a recent National Institutes of Health, National Heart, Lung, and Blood Institute initiative on integrative mitochondrial biology in cardiovascular diseases, we reflect on the accomplishments made possible by this unique interdisciplinary collaboration effort and exciting new fronts on the study of these remarkable organelles.
C1 [Ping, Peipei; Cai, Hua; Weiss, James N.] UCLA David Geffen Sch Med, Dept Physiol, Los Angeles, CA USA.
[Ping, Peipei; Cai, Hua; Weiss, James N.] UCLA David Geffen Sch Med, Dept Med, Los Angeles, CA USA.
[Gustafsson, Asa B.] Univ Calif San Diego, Dept Pharmacol, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA USA.
[Bers, Don M.] Univ Calif Davis, Dept Pharmacol, Davis, CA USA.
[Blatter, Lothar A.] Rush Univ, Med Ctr, Dept Mol Biophys & Physiol, Chicago, IL 60612 USA.
[Jahangir, Arshad] Aurora Hlth Care, Ctr Integrat Res Cardiovasc Aging, Cardiovasc Serv, Milwaukee, WI USA.
[Jahangir, Arshad] Aurora Hlth Care, Dept Res, Milwaukee, WI USA.
[Kelly, Daniel] Sanford Burnham Med Res Inst, Diabet & Obes Res Ctr, Orlando, FL USA.
[Muoio, Deborah] Duke Univ, Dept Med, Durham, NC USA.
[O'Rourke, Brian; Van Eyk, Jennifer] Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA.
[Trayanova, Natalia] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA.
[Rabinovitch, Peter] Univ Washington, Dept Pathol, Seattle, WA 98195 USA.
[Wong, Renee; Longacre, Lisa Schwartz] NHLBI, Heart Failure & Arrhythmia Branch, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
RP Longacre, LS (reprint author), NHLBI, Heart Failure & Arrhythmia Branch, Div Cardiovasc Sci, NIH, 6701 Rockledge Dr,MSC 7956, Bethesda, MD 20892 USA.
EM schwartzlongal@mail.nih.gov
OI Bers, Donald/0000-0002-2237-9483
FU National Heart, Lung, and Blood Institute Mitochondria in Heart Diseases
Initiative [RFA-HL-10-002, R01-HL101217, R01-HL101240, R01-HL101189,
R01-HL101235, R01-HL101228, R01-HL101186]
FX The investigators of cited works were supported by the National Heart,
Lung, and Blood Institute Mitochondria in Heart Diseases Initiative
(RFA-HL-10-002); grant numbers R01-HL101217, R01-HL101240, R01-HL101189,
R01-HL101235, R01-HL101228, and R01-HL101186.
NR 12
TC 2
Z9 2
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7330
EI 1524-4571
J9 CIRC RES
JI Circ.Res.
PD JUL 17
PY 2015
VL 117
IS 3
BP 234
EP 238
DI 10.1161/CIRCRESAHA.117.306693
PG 5
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA CM9QZ
UT WOS:000358045300004
PM 26185209
ER
PT J
AU Lauer, MS
Danthi, NS
Kaltman, J
Wu, CL
AF Lauer, Michael S.
Danthi, Narasimhan S.
Kaltman, Jonathan
Wu, Colin
TI Predicting Productivity Returns on Investment Thirty Years of Peer
Review, Grant Funding, and Publication of Highly Cited Papers at the
National Heart, Lung, and Blood Institute
SO CIRCULATION RESEARCH
LA English
DT Article
DE bibliometrics; National Institutes of Health (US); National Heart, Lung,
and Blood Institute (US); peer review; ROC curve
ID CARDIOVASCULAR R01 GRANTS; CITATION IMPACT; PERCENTILE RANKING; SCIENCE;
PROPOSALS; SCRUTINY; TRIALS; PEOPLE; PANELS
AB There are conflicting data about the ability of peer review percentile rankings to predict grant productivity, as measured through publications and citations. To understand the nature of these apparent conflicting findings, we analyzed bibliometric outcomes of 6873 de novo cardiovascular R01 grants funded by the National Heart, Lung, and Blood Institute (NHLBI) between 1980 and 2011. Our outcomes focus on top-10% articles, meaning articles that were cited more often than 90% of other articles on the same topic, of the same type (eg, article, editorial), and published in the same year. The 6873 grants yielded 62468 articles, of which 13507 (or 22%) were top-10% articles. There was a modest association between better grant percentile ranking and number of top-10% articles. However, discrimination was poor (area under receiver operating characteristic curve [ROC], 0.52; 95% confidence interval, 0.51-0.53). Furthermore, better percentile ranking was also associated with higher annual and total inflation-adjusted grant budgets. There was no association between grant percentile ranking and grant outcome as assessed by number of top-10% articles per $million spent. Hence, the seemingly conflicting findings on peer review percentile ranking of grants and subsequent productivity largely reflect differing questions and outcomes. Taken together, these findings raise questions about how best National Institutes of Health (NIH) should use peer review assessments to make complex funding decisions.
C1 [Lauer, Michael S.] NHLBI, Off Director, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Danthi, Narasimhan S.] NHLBI, Adv Technol & Surg Branch, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Kaltman, Jonathan] NHLBI, Heart Dev & Struct Dis Branch, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Wu, Colin] NHLBI, Off Biostat Res, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
RP Lauer, MS (reprint author), 6701 Rockledge Dr,Room 8128, Bethesda, MD 20892 USA.
EM lauerm@nhlbi.nih.gov
FU Intramural NIH HHS [Z99 HL999999]
NR 25
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U1 2
U2 20
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7330
EI 1524-4571
J9 CIRC RES
JI Circ.Res.
PD JUL 17
PY 2015
VL 117
IS 3
BP 239
EP 243
DI 10.1161/CIRCRESAHA.115.306830
PG 5
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA CM9QZ
UT WOS:000358045300005
PM 26089369
ER
PT J
AU Lewis, KL
Han, PKJ
Hooker, GW
Klein, WMP
Biesecker, LG
Biesecker, BB
AF Lewis, Katie L.
Han, Paul K. J.
Hooker, Gillian W.
Klein, William M. P.
Biesecker, Leslie G.
Biesecker, Barbara B.
TI Characterizing Participants in the ClinSeq Genome Sequencing Cohort as
Early Adopters of a New Health Technology
SO PLOS ONE
LA English
DT Article
ID PERSONAL GENOMICS; RISK; MEDICINE; OPTIMISM; INTENTIONS; PSYCHOLOGY;
AMBIGUITY; FAMILIES
AB Genome sequencing is a novel clinical tool that has the potential to identify genetic origins of disease. However, the complexities of this new technology are significant and little is known about its integration into clinical care, and its potential adoption by patients. Expectations of its promise for personalized medicine are high and it is important to properly match expectations to the realities of the test. The NIH ClinSeq cohort study pilots the integration of genome sequencing into clinical research and care to assess the technical, medical and socio-behavioral aspects of implementing this technology. Over 950 adults ages 45-65 have been enrolled and clinically phenotyped. As an initial study, we describe the personality traits of ClinSeq participants, and explore how these traits compare to those that characterize early adopters of other new technologies. Our analysis was conducted on responses from 630 members of the cohort who completed a baseline survey on health cognitions, affect, health-related behaviors and personality traits, prior to receipt of any genome sequencing results. The majority of participants were white (90.5%), had at least a college degree (86.5%), and had at least one biological child (74.6%). Members of this ClinSeq sample were found to be high in dispositional optimism and resilience. Their high SES paralleled that of other early adopters of new technology. These attributes may contribute to participants' expectations for favorable outcomes and willingness to take higher risks when compared to the general population. These characteristics may distinguish those who are most likely to pursue genome sequencing and be indicative of their psychological resources to manage returned results.
C1 [Lewis, Katie L.; Biesecker, Leslie G.; Biesecker, Barbara B.] NHGRI, Med Genom & Metab Genet Branch, Bethesda, MD 20892 USA.
[Han, Paul K. J.] Ctr Outcomes Res & Evaluat, Maine Med Ctr Res Inst, Scarborough, ME USA.
[Hooker, Gillian W.; Biesecker, Barbara B.] NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA.
[Hooker, Gillian W.] NextGxDx, Franklin, TN USA.
[Klein, William M. P.] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA.
RP Lewis, KL (reprint author), NHGRI, Med Genom & Metab Genet Branch, Bethesda, MD 20892 USA.
EM lewiskatie@mail.nih.gov
OI Han, Paul/0000-0003-0165-1940
FU Intramural Research Program of the National Human Genome Research
Institute, National Institutes of Health
FX This study was funded by the Intramural Research Program of the National
Human Genome Research Institute, National Institutes of Health. NextGxDx
provided support in the form of salary for one author (GWH) during the
time that this manuscript was prepared, but did not have any additional
role in the study design, data collection and analysis, decision to
publish or preparation of the manuscript. The specific roles of that
author are articulated in the 'author contributions' section.
NR 46
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U1 1
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 17
PY 2015
VL 10
IS 7
AR e0132690
DI 10.1371/journal.pone.0132690
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN1RV
UT WOS:000358198700055
PM 26186621
ER
PT J
AU Yu, SJ
Reiner, D
Shen, H
Wu, KJ
Liu, QR
Wang, Y
AF Yu, Seong-Jin
Reiner, David
Shen, Hui
Wu, Kou-Jen
Liu, Qing-Rong
Wang, Yun
TI Time-Dependent Protection of CB2 Receptor Agonist in Stroke
SO PLOS ONE
LA English
DT Article
ID TRANSIENT FOCAL ISCHEMIA; MIDDLE CEREBRAL-ARTERY; CANNABINOID RECEPTORS;
MICROGLIAL CELLS; BINDING-SITES; RAT-BRAIN; ACTIVATION; INFARCTION;
NEUROPROTECTION; LOCALIZATION
AB Recent studies have indicated that type 2 cannabinoid receptor (CB2R) agonists reduce neurodegeneration after brain injury through anti-inflammatory activity. The purpose of this study was to examine the time-dependent interaction of CB2R and inflammation in stroke brain. Adult male rats were subjected to right middle cerebral artery occlusion (MCAo). CB2R mRNA expression was significantly elevated >20 fold on day 2, peaked >40-fold on day 5, and normalized on day 10 post-stroke. Inflammatory markers IBA1 and TLR4 were significantly upregulated 15 fold until day 5 after MCAo. Because of the delayed upregulation of CB2R and IBA1, we next treated animals daily with CB2R agonist AM1241 or anti-inflammatory PPAR-gamma agonist pioglitazone from 2 to 5 days after MCAo. Delayed treatment with pioglitazone significantly reduced abnormal neurological scores and body asymmetry as well as brain infarction in stroke animals. No behavioral improvement or reduction in brain infarction was found in animals receiving AM1241. Pioglitazone, but not AM1241, significantly reduced IBA1 expression in the stroke cortex, suggesting that delayed treatment with AM1241 failed to alter ischemia-mediated IBA-1 upregulation. In contrast, pretreatment with AM1241 significantly reduced brain infarction and neurological deficits. In conclusion, our data support a time-dependent neuroprotection of CB2 agonist in an animal model of stroke. Delayed post- treatment with PPAR-gamma agonist induced behavioral recovery and microglial suppression; early treatment with CB2R agonist suppressed neurodegeneration in stroke animals.
C1 [Yu, Seong-Jin; Wu, Kou-Jen; Wang, Yun] Natl Hlth Res Inst, Ctr Neuropsychiat, Zhunan, Taiwan.
[Reiner, David; Shen, Hui; Liu, Qing-Rong; Wang, Yun] Natl Inst Drug Abuse, Neural Protect & Regenerat Sect, NIH, Baltimore, MD USA.
RP Wang, Y (reprint author), Natl Hlth Res Inst, Ctr Neuropsychiat, Zhunan, Taiwan.
EM ywang@nhri.org.tw
RI Liu, Qing-Rong/A-3059-2012
OI Liu, Qing-Rong/0000-0001-8477-6452
FU Ministry of Science and Technology, Taiwan [MOST 03-2314-B-400-016-MY2];
National Institute on Drug Abuse, NIH, USA
FX Funding for this study was received from the Ministry of Science and
Technology, Taiwan (MOST 03-2314-B-400-016-MY2) and from the National
Institute on Drug Abuse, NIH, USA (intramural). 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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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 JUL 17
PY 2015
VL 10
IS 7
AR e0132487
DI 10.1371/journal.pone.0132487
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN1RV
UT WOS:000358198700045
PM 26186541
ER
PT J
AU Perez-Pinera, P
Jones, MF
Lal, A
Lu, TK
AF Perez-Pinera, Pablo
Jones, Matthew F.
Lal, Ashish
Lu, Timothy K.
TI Putting Non-coding RNA on Display with CRISPR
SO MOLECULAR CELL
LA English
DT Editorial Material
ID TRANSCRIPTION FACTORS; ACTIVATION
AB In a recent issue of Nature Methods, Shechner et al. (2015) reported the development of CRISPR Display (CRISP-Disp), which is a sophisticated, flexible, modular, and multiplexable platform for targeting different types of non-coding RNAs (ncRNAs) to genomic loci. CRISP-Disp will facilitate synthetic-biology applications and enable the elucidation of ncRNA functions.
C1 [Perez-Pinera, Pablo] Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA.
[Jones, Matthew F.; Lal, Ashish] NCI, Regulatory RNAs & Canc Sect, Genet Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Lu, Timothy K.] MIT, Dept Elect Engn & Comp Sci, Dept Biol Engn, Elect Res Lab, Cambridge, MA 02139 USA.
RP Lu, TK (reprint author), MIT, Dept Elect Engn & Comp Sci, Dept Biol Engn, Elect Res Lab, Cambridge, MA 02139 USA.
EM timlu@mit.edu
NR 10
TC 1
Z9 1
U1 2
U2 17
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 JUL 16
PY 2015
VL 59
IS 2
BP 146
EP 148
DI 10.1016/j.molcel.2015.07.002
PG 3
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CT0AV
UT WOS:000362457000004
PM 26186289
ER
PT J
AU Egan, DF
Chun, MGH
Vamos, M
Zou, HX
Rong, J
Miller, CJ
Lou, HJ
Raveendra-Panickar, D
Yang, CC
Sheffler, DJ
Teriete, P
Asara, JM
Turk, BE
Cosford, NDP
Shaw, RJ
AF Egan, Daniel F.
Chun, Matthew G. H.
Vamos, Mitchell
Zou, Haixia
Rong, Juan
Miller, Chad J.
Lou, Hua Jane
Raveendra-Panickar, Dhanya
Yang, Chih-Cheng
Sheffler, Douglas J.
Teriete, Peter
Asara, John M.
Turk, Benjamin E.
Cosford, Nicholas D. P.
Shaw, Reuben J.
TI Small Molecule Inhibition of the Autophagy Kinase ULK1 and
Identification of ULK1 Substrates
SO MOLECULAR CELL
LA English
DT Article
ID DIRECT PHOSPHORYLATION; MAMMALIAN TARGET; MTOR; PROTEIN; AMPK; CANCER;
BINDING; COMPLEX; POTENT; ATG101
AB Many tumors become addicted to autophagy for survival, suggesting inhibition of autophagy as a potential broadly applicable cancer therapy. ULK1/Atg1 is the only serine/threonine kinase in the core autophagy pathway and thus represents an excellent drug target. Despite recent advances in the understanding of ULK1 activation by nutrient deprivation, how ULK1 promotes autophagy remains poorly understood. Here, we screened degenerate peptide libraries to deduce the optimal ULK1 substrate motif and discovered 15 phosphorylation sites in core autophagy proteins that were verified as in vivo ULK1 targets. Weutilized these ULK1 substrates to perform a cell-based screen to identify and characterize a potent ULK1 small molecule inhibitor. The compound SBI-0206965 is a highly selective ULK1 kinase inhibitor in vitro and suppressed ULK1-mediated phosphorylation events in cells, regulating autophagy and cell survival. SBI-0206965 greatly synergized with mechanistic target of rapamycin (mTOR) inhibitors to kill tumor cells, providing a strong rationale for their combined use in the clinic.
C1 [Egan, Daniel F.; Chun, Matthew G. H.; Shaw, Reuben J.] Salk Inst Biol Studies, Mol & Cell Biol Lab, La Jolla, CA 92037 USA.
[Shaw, Reuben J.] Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USA.
[Egan, Daniel F.; Chun, Matthew G. H.; Vamos, Mitchell; Zou, Haixia; Rong, Juan; Raveendra-Panickar, Dhanya; Sheffler, Douglas J.; Teriete, Peter; Cosford, Nicholas D. P.] NCI, Cell Death & Survival Networks Res Program, Designated Canc Ctr, Sanford Burnham Med Res Inst, La Jolla, CA 92037 USA.
[Miller, Chad J.; Lou, Hua Jane; Turk, Benjamin E.] Yale Univ, Dept Pharmacol, Sch Med, New Haven, CT 06520 USA.
[Asara, John M.] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA.
[Asara, John M.] Harvard Univ, Dept Med, Sch Med, Boston, MA 02115 USA.
[Yang, Chih-Cheng] Sanford Burnham Med Res Inst, Funct Genom Core, La Jolla, CA 92037 USA.
RP Cosford, NDP (reprint author), NCI, Cell Death & Survival Networks Res Program, Designated Canc Ctr, Sanford Burnham Med Res Inst, 10901 North Torrey Pines Rd, La Jolla, CA 92037 USA.
EM ncosford@sanfordburnham.org; shaw@salk.edu
FU predoctoral T32 CMG training grant; American Cancer Society
[122862-PF-12-258-01-TBG]; NIH [R01CA188694, R01GM104047, R01CA172229];
Department of Defense (DoD) [W81XWH-13-1-0043]; Howard Hughes Medical
Institute; Salk CCSG [P30 CA014195]; Leona M. and Harry B. Helmsley
Charitable Trust [2012-PG-MED002]
FX We thank Dr. Gary Kasof at Cell Signaling Technology for developing the
Phospho-VPS34 Ser249 antibody in conjunction with D.F.E. and R.J.S. We
thank Drs. Craig Thompson (MSKCC) for the Ulk1/2 MEFs (Cheong et al.,
2011) and Dr. Wei-Xing Zong (SUNY Stony Brook) for the Vps34-floxed MEFs
(Jaber et al., 2012). We thank Pedro Aza-Blanc in the Functional
Genomics core at the Sanford Burnham Medical Research Institute for
assistance with the GFP-LC3 quantitation. D.F.E. was supported by the
predoctoral T32 CMG training grant to UCSD/Salk. M.G.H.C. was supported
by a postdoctoral fellowship from the American Cancer Society
(122862-PF-12-258-01-TBG). This work is supported in part by NIH grants
R01CA188694 to N.D.P.C., R01GM104047 to B.E.T., and R01CA172229 and
Department of Defense (DoD) grant W81XWH-13-1-0043 to R.J.S. Work in the
laboratory of R.J.S. was also supported in part through the Howard
Hughes Medical Institute, the Salk CCSG P30 CA014195, and the Leona M.
and Harry B. Helmsley Charitable Trust grant #2012-PG-MED002.
NR 42
TC 46
Z9 48
U1 8
U2 30
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 JUL 16
PY 2015
VL 59
IS 2
BP 285
EP 297
DI 10.1016/j.molcel.2015.05.031
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CT0AV
UT WOS:000362457000015
PM 26118643
ER
PT J
AU Meissner, EG
Decalf, J
Casrouge, A
Masur, H
Kottilil, S
Albert, ML
Duffy, D
AF Meissner, Eric G.
Decalf, Jeremie
Casrouge, Armanda
Masur, Henry
Kottilil, Shyam
Albert, Matthew L.
Duffy, Darragh
TI Dynamic Changes of Post-Translationally Modified Forms of CXCL10 and
Soluble DPP4 in HCV Subjects Receiving Interferon-Free Therapy
SO PLOS ONE
LA English
DT Article
ID CHRONIC HEPATITIS-C; GENOTYPE 1 INFECTION; VIRUS-INFECTION; SPONTANEOUS
CLEARANCE; PREDICTIVE-VALUE; ASSOCIATION; PROTEIN-10; CHEMOKINES;
RIBAVIRIN; INDUCTION
AB Serum levels of the interferon (IFN)-stimulated chemokine CXCL10 are increased during chronic HCV infection and associate with outcome of IFN-based therapy. Elevated levels of NH2-terminal truncated CXCL10 (3-77aa), produced by DPP4 cleavage, negatively associate with spontaneous clearance of acute HCV infection and sustained virological response (SVR) with IFN-based therapy for chronic infection. The association of different CXCL10 forms and DPP4 with outcome during IFN-free HCV therapy has not been examined. Using novel Simoa assays, plasma was analyzed from HCV genotype-1 (GT1) subjects who relapsed (n = 11) or achieved SVR (n = 10) after sofosbuvir and ribavirin (SOF/RBV) treatment, and from SOF/RBV relapsers who achieved SVR with a subsequent SOF/ledipasvir regimen (n = 9). While the NH2-truncated form of CXCL10 was elevated in HCV infection relative to healthy controls, pre-treatment plasma concentrations of CXCL10 forms failed to stratify subjects based on treatment outcome to IFN-free regimens. However, a trend (statistically non-significant) towards elevated higher levels of total and long CXCL10 was observed pre-treatment in subjects who relapsed. All forms of CXCL10 decreased rapidly following treatment initiation and were again elevated in subjects who experienced HCV relapse, indicating that CXCL10 production may be associated with active viral replication. While soluble DPP4 (sDPP4) and NH2-truncated CXCL10 concentrations were highly correlated, on-treatment sDPP4 levels and activity declined more slowly than CXCL10, suggesting differential regulation.
C1 [Meissner, Eric G.] Med Univ S Carolina, Dept Microbiol & Immunol, Div Infect Dis, Charleston, SC 29425 USA.
[Meissner, Eric G.; Kottilil, Shyam] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Meissner, Eric G.; Masur, Henry] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA.
[Decalf, Jeremie; Casrouge, Armanda; Albert, Matthew L.; Duffy, Darragh] Inst Pasteur, Lab Dendrit Cell Immunobiol, Paris, France.
[Decalf, Jeremie; Casrouge, Armanda; Albert, Matthew L.; Duffy, Darragh] INSERM, U818, Paris, France.
[Kottilil, Shyam] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA.
[Albert, Matthew L.; Duffy, Darragh] Inst Pasteur, Ctr Human Immunol, Paris, France.
RP Meissner, EG (reprint author), Med Univ S Carolina, Dept Microbiol & Immunol, Div Infect Dis, Charleston, SC 29425 USA.
EM meissner@musc.edu; darragh.duffy@pasteur.fr
FU National Institute of Allergy and Infectious Diseases; PasteurInnov
grant (Institut Pasteur); European Union [601851]
FX This project was supported by federal funds from the intramural program
of the National Institute of Allergy and Infectious Diseases, a
PasteurInnov grant (Institut Pasteur), and the European Union FP7 grant
PoC-HCV (GA no 601851). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 25
TC 7
Z9 7
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 JUL 16
PY 2015
VL 10
IS 7
AR e0133236
DI 10.1371/journal.pone.0133236
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN1RQ
UT WOS:000358198200059
PM 26181438
ER
PT J
AU Blaho, VA
Galvani, S
Engelbrecht, E
Liu, C
Swendeman, SL
Kono, M
Proia, RL
Steinman, L
Han, MH
Hla, T
AF Blaho, Victoria A.
Galvani, Sylvain
Engelbrecht, Eric
Liu, Catherine
Swendeman, Steven L.
Kono, Mari
Proia, Richard L.
Steinman, Lawrence
Han, May H.
Hla, Timothy
TI HDL-bound sphingosine-1-phosphate restrains lymphopoiesis and
neuroinflammation
SO NATURE
LA English
DT Article
ID SPHINGOSINE 1-PHOSPHATE RECEPTOR; HEMATOPOIETIC STEM-CELLS; SERUM-LIPID
PROFILES; MULTIPLE-SCLEROSIS; APOLIPOPROTEIN-M; LYMPHOCYTE EGRESS;
BONE-MARROW; QUANTITATIVE-ANALYSIS; CHOLESTEROL EFFLUX; S1P RECEPTOR-1
AB Lipid mediators influence immunity in myriad ways. For example, circulating sphingosine-1-phosphate (S1P) is a key regulator of lymphocyte egress(1,2). Although the majority of plasma S1P is bound to apolipoprotein M (ApoM) in the high-density lipoprotein (HDL) particle(3), the immunological functions of the ApoM-S1P complex are unknown. Here we show that ApoM-S1P is dispensable for lymphocyte trafficking yet restrains lymphopoiesis by activating the S1P1 receptor on bone marrow lymphocyte progenitors. Mice that lacked ApoM (Apom(-/-)) had increased proliferation of Lin(-) Sca-1(+) cKit(+) haematopoietic progenitor cells (LSKs) and common lymphoid progenitors (CLPs) in bone marrow. Pharmacological activation or genetic overexpression of S1P(1) suppressed LSK and CLP cell proliferation in vivo. ApoM was stably associated with bone marrow CLPs, which showed active S1P(1) signalling in vivo(4). Moreover, ApoM-bound S1P, but not albumin-bound S1P, inhibited lymphopoiesis in vitro. Upon immune stimulation, Apom(-/-) mice developed more severe experimental autoimmune encephalomyelitis5, characterized by increased lymphocytes in the central nervous system and breakdown of the blood-brain barrier. Thus, the ApoM-S1P-S1P(1) signalling axis restrains the lymphocyte compartment and, subsequently, adaptive immune responses. Unique biological functions imparted by specific S1P chaperones could be exploited for novel therapeutic opportunities.
C1 [Blaho, Victoria A.; Galvani, Sylvain; Engelbrecht, Eric; Liu, Catherine; Swendeman, Steven L.; Hla, Timothy] Cornell Univ, Weill Med Coll, Dept Pathol & Lab Med, Ctr Vasc Biol, New York, NY 10065 USA.
[Blaho, Victoria A.; Hla, Timothy] Cornell Univ, Weill Med Coll, Brain & Mind Res Inst, New York, NY 10065 USA.
[Kono, Mari; Proia, Richard L.] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
[Steinman, Lawrence; Han, May H.] Stanford Univ, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA.
RP Hla, T (reprint author), Cornell Univ, Weill Med Coll, Dept Pathol & Lab Med, Ctr Vasc Biol, New York, NY 10065 USA.
EM tih2002@med.cornell.edu
RI Hla, Timothy/G-5873-2012
OI Hla, Timothy/0000-0001-8355-4065
FU National Institutes of Health (NIH) [F32 CA14211]; New York Stem Cell
Foundation [C026878]; NIH, Fondation Leducq [HL67330, HL70694, HL89934];
Intramural program of the National Institute of Diabetes and Digestive
and Kidney Diseases, NIH; Fondation Leducq; Lipidomics Shared Resource,
Hollings Cancer Center, Medical University of South Carolina [P30
CA138313]; Lipidomics Core in the SC Lipidomics and Pathobiology COBRE
[P20 RR017677]
FX The authors thank C. Nathan, G. Koretzky and R. Nachman for critical
comments, C. Christoffersen and L. B. Nielsen for the Apom-/-
and APOMTg mice and discussions, V. Brinkmann and Novartis
Pharma AG for gifts of FTY720 and AUY954, M. Sanson for help with HDL
purification, Y. Huang for help with the EAE model and J. McCormick for
assistance with fluorescence-activated cell sorting. V. A. B. is a Leon
Levy Research Fellow of the Weill Cornell Medical College Brain and Mind
Institute. Research was supported by grants to V. A. B. (National
Institutes of Health (NIH) F32 CA14211 and New York Stem Cell Foundation
C026878), T.H. (NIH HL67330, HL70694 and HL89934, Fondation Leducq),
R.L.P. (Intramural program of the National Institute of Diabetes and
Digestive and Kidney Diseases, NIH and Fondation Leducq), M.H. and L.S.
(Fondation Leducq), the Lipidomics Shared Resource, Hollings Cancer
Center, Medical University of South Carolina (P30 CA138313) and the
Lipidomics Core in the SC Lipidomics and Pathobiology COBRE (P20
RR017677).
NR 48
TC 27
Z9 28
U1 2
U2 19
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 JUL 16
PY 2015
VL 523
IS 7560
BP 342
EP +
DI 10.1038/nature14462
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CM8KY
UT WOS:000357950900041
PM 26053123
ER
PT J
AU Klein, HG
Cortes-Puch, I
Natanson, C
AF Klein, Harvey G.
Cortes-Puch, Irene
Natanson, Charles
TI More on the Age of Transfused Red Cells
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
ID BLOOD
C1 [Klein, Harvey G.; Cortes-Puch, Irene; Natanson, Charles] NIH, Bethesda, MD 20892 USA.
RP Klein, HG (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
EM hklein@dtm.cc.nih.gov
NR 5
TC 7
Z9 7
U1 3
U2 5
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUL 16
PY 2015
VL 373
IS 3
BP 283
EP 283
DI 10.1056/NEJMc1505699
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA CM8MS
UT WOS:000357956200018
PM 26176391
ER
PT J
AU Lee, M
Cho, SN
Barry, CE
AF Lee, Myungsun
Cho, Sang Nae
Barry, Clifton E., III
TI Linezolid for XDR-TB - Final Study Outcomes
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
ID TUBERCULOSIS; TOLERABILITY; EFFICACY; SAFETY
C1 [Lee, Myungsun] Int TB Res Ctr, Chang Won, South Korea.
[Cho, Sang Nae] Yonsei Univ, Coll Med, Seoul 120749, South Korea.
[Barry, Clifton E., III] NIAID, Bethesda, MD 20892 USA.
RP Lee, M (reprint author), Int TB Res Ctr, Chang Won, South Korea.
EM cbarry@niaid.nih.gov
RI Barry, III, Clifton/H-3839-2012
NR 5
TC 15
Z9 15
U1 1
U2 6
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUL 16
PY 2015
VL 373
IS 3
BP 290
EP 291
DI 10.1056/NEJMc1500286
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA CM8MS
UT WOS:000357956200029
PM 26176401
ER
PT J
AU Cai, Y
Yoneda, M
Tomita, T
Kurotani, R
Okamoto, M
Kido, T
Abe, H
Mitzner, W
Guha, A
Kimura, S
AF Cai, Yan
Yoneda, Mitsuhiro
Tomita, Takeshi
Kurotani, Reiko
Okamoto, Minoru
Kido, Taketomo
Abe, Hiroyuki
Mitzner, Wayne
Guha, Arjun
Kimura, Shioko
TI Transgenically-expressed secretoglobin 3A2 accelerates resolution of
bleomycin-induced pulmonary fibrosis in mice
SO BMC PULMONARY MEDICINE
LA English
DT Article
DE Secretoglobin; SCGB; SCGB3A2; Bleomycin-induced pulmonary fibrosis
model; Spontaneous resolution of bleomycin-induced pulmonary fibrosis;
Transgenic mouse
ID UTEROGLOBIN-RELATED PROTEIN-1; ALLERGIC AIRWAY INFLAMMATION;
TRANSCRIPTIONAL ELEMENTS; LUNG DEVELOPMENT; II CELLS; MOUSE; GENE;
MARKER; SUPERFAMILY; MODEL
AB Background: Secretoglobin (SCGB) 3A2, a cytokine-like secretory protein of small molecular weight, is predominantly expressed in airway epithelial cells. While SCGB3A2 is known to have anti-inflammatory, growth factor, and anti-fibrotic activities, whether SCGB3A2 has any other roles, particularly in lung homeostasis and disease has not been demonstrated in vivo. The aim of this study was to address these questions in mice.
Methods: A transgenic mouse line that expresses SCGB3A2 in the lung using the human surfactant protein-C promoter was established. Detailed histological, immunohistochemical, physiological, and molecular characterization of the Scgb3a2-transgenic mouse lungs were carried out. Scgb3a2-transgenic and wild-type mice were subjected to bleomycin-induced pulmonary fibrosis model, and their lungs and bronchoalveolar lavage fluids were collected at various time points during 9 weeks post-bleomycin treatment for further analysis.
Results: Adult Scgb3a2-transgenic mouse lungs expressed approximately five-fold higher levels of SCGB3A2 protein in comparison to wild-type mice as determined by western blotting of lung tissues. Immunohistochemistry showed that expression was localized to alveolar type II cells in addition to airway epithelial cells, thus accurately reflecting the site of surfactant protein-C expression. Scgb3a2-transgenic mice showed normal lung development and histology, and no overt gross phenotypes. However, when subjected to a bleomycin-induced pulmonary fibrosis model, they initially exhibited exacerbated fibrosis at 3 weeks post-bleomycin administration that was more rapidly resolved by 6 weeks as compared with wild-type mice, as determined by lung histology, Masson Trichrome staining and hydroxyproline content, inflammatory cell numbers, expression of collagen genes, and proinflammatory cytokine levels. The decrease of fibrosis coincided with the increased expression of SCGB3A2 in Scgb3a2-transgenic lungs.
Conclusions: These results demonstrate that SCGB3A2 is an anti-fibrotic agent, and suggest a possible therapeutic use of recombinant SCGB3A2 in the treatment of pulmonary fibrosis.
C1 [Cai, Yan; Yoneda, Mitsuhiro; Tomita, Takeshi; Kurotani, Reiko; Okamoto, Minoru; Kido, Taketomo; Kimura, Shioko] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA.
[Kurotani, Reiko; Abe, Hiroyuki] Yamagata Univ, Grad Sch Sci & Engn, Biochem Engn, Yonezawa, Yamagata 9928510, Japan.
[Mitzner, Wayne] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
[Guha, Arjun] Boston Univ, Dept Med, Ctr Pulm, Sch Med, Boston, MA 02118 USA.
[Cai, Yan] NIAAA, Lab Liver Dis, NIH, Bethesda, MD 20892 USA.
[Tomita, Takeshi] Tokyo Womens Med Univ, Dept Pharmacol, Tokyo 1628666, Japan.
[Okamoto, Minoru] Rakuno Gakuen Univ, Sch Vet Med, Dept Vet Immunopathol, Ebetsu, Hokkaido 0698501, Japan.
[Kido, Taketomo] Univ Tokyo, Inst Mol & Cellular Biosci, Lab Cell Growth & Differentiat, Tokyo 1130032, Japan.
RP Kimura, S (reprint author), NCI, Lab Metab, NIH, Bethesda, MD 20892 USA.
EM kimuras@mail.nih.gov
RI Cai, Yan/P-4383-2015
FU National Cancer Institute
FX We thank Jeffrey Whitsett (Cincinnati, OH) for the human SP-C gene
promoter plasmid and Poonam Mannan, Langston Lim, and Susan H. Garfield
(CCR Confocal Microscopy Core Facility, Laboratory of Cancer Biology and
Genetics, NCI) for their help in confocal microscopy. This study was
funded by the Intramural Research Program of the National Cancer
Institute.
NR 37
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Z9 2
U1 1
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2466
J9 BMC PULM MED
JI BMC Pulm. Med.
PD JUL 16
PY 2015
VL 15
AR 72
DI 10.1186/s12890-015-0065-4
PG 13
WC Respiratory System
SC Respiratory System
GA CM7ZC
UT WOS:000357914100001
PM 26178733
ER
PT J
AU Quang, DX
Erdos, MR
Parker, SCJ
Collins, FS
AF Quang, Daniel X.
Erdos, Michael R.
Parker, Stephen C. J.
Collins, Francis S.
TI Motif signatures in stretch enhancers are enriched for
disease-associated genetic variants
SO EPIGENETICS & CHROMATIN
LA English
DT Article
ID HUMAN TRANSCRIPTION FACTORS; PROTEIN-DNA INTERACTIONS; SUPER-ENHANCERS;
BINDING SPECIFICITIES; REGULATORY ELEMENTS; OPEN CHROMATIN; CELL
IDENTITY; HUMAN GENOME; IN-VIVO; SEQ
AB Background: Stretch enhancers (SEs) are large chromatin-defined regulatory elements that are at least 3,000 base pairs (bps) long, in contrast to the median enhancer length of 800 bps. SEs tend to be cell-type specific, regulate cell-type specific gene expression, and are enriched in disease-associated genetic variants in disease-relevant cell types. Transcription factors (TFs) can bind to enhancers to modulate enhancer activity, and their sequence specificity can be represented by motifs. We hypothesize motifs can provide a biological context for how genetic variants contribute to disease.
Results: We integrated chromatin state, gene expression, and chromatin accessibility [measured as DNase I Hypersensitive Sites (DHSs)] maps across nine different cell types. Motif enrichment analyses of chromatin-defined enhancer sequences identify several known cell-type specific "master" factors. Furthermore, de novo motif discovery not only recovers many of these motifs, but also identifies novel non-canonical motifs, providing additional insight into TF binding preferences. Across the length of SEs, motifs are most enriched in DHSs, though relative enrichment is also observed outside of DHSs. Interestingly, we show that single nucleotide polymorphisms associated with diseases or quantitative traits significantly overlap motif occurrences located in SEs, but outside of DHSs.
Conclusions: These results reinforce the role of SEs in influencing risk for diseases and suggest an expanded regulatory functional role for motifs that occur outside highly accessible chromatin. Furthermore, the motif signatures generated here expand our understanding of the binding preference of well-characterized TFs.
C1 [Quang, Daniel X.] Univ Calif Irvine, Dept Comp Sci, Irvine, CA 92697 USA.
[Quang, Daniel X.] Univ Calif Irvine, Ctr Complex Biol Syst, Irvine, CA 92697 USA.
[Erdos, Michael R.; Collins, Francis S.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Parker, Stephen C. J.] Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.
[Parker, Stephen C. J.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.
RP Parker, SCJ (reprint author), Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.
EM scjp@umich.edu
OI Quang, Daniel/0000-0002-7660-990X
FU NIH [1-ZIA-HG000024, R00DK099240-02]; American Diabetes Association
[1-14-INI-07]; National Institute of Biomedical Imaging and
Bioengineering, National Research Service Award from the University of
California, Irvine [EB009418]; Center for Complex Biological Systems
[NIH R01HG006870]; National Science Foundation Graduate Research
Fellowship [DGE-1321846]; Intramural Research Program of the National
Human Genome Research Institute, National Institutes of Health
FX We thank Peter S. Chines, Narisu Narisu, and Brooke N. Wolford for
helpful advice. This work was supported by NIH grants 1-ZIA-HG000024 (to
FSC) and R00DK099240-02 (to SCJP), the American Diabetes Association
Pathway to Stop Diabetes Grant 1-14-INI-07 (to SCJP), and the National
Institute of Biomedical Imaging and Bioengineering, National Research
Service Award (EB009418) from the University of California, Irvine,
Center for Complex Biological Systems (NIH R01HG006870, to DXQ). This
material is based upon work supported by the National Science Foundation
Graduate Research Fellowship under Grant No. (DGE-1321846, to DXQ). Any
opinion, findings, and conclusions or recommendations expressed in this
material are those of the authors(s) and do not necessarily reflect the
views of the National Science Foundation. This research was supported
(in part) by the Intramural Research Program of the National Human
Genome Research Institute, National Institutes of Health.
NR 43
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Z9 5
U1 0
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1756-8935
J9 EPIGENET CHROMATIN
JI Epigenetics Chromatin
PD JUL 16
PY 2015
VL 8
AR 23
DI 10.1186/s13072-015-0015-7
PG 14
WC Genetics & Heredity
SC Genetics & Heredity
GA CM7YJ
UT WOS:000357912100001
PM 26180553
ER
PT J
AU Kaur, A
Marchbank, K
Dang, V
O'Connell, M
Webster, M
Appleton, J
Cheng, P
Valiga, A
Morissette, R
McDonnell, N
Ferrucci, L
Kossenkov, A
Meeth, K
Bosenberg, M
Tang, HY
Yin, XF
Wood, W
Lehrmann, E
Becker, K
Flaherty, K
Frederick, D
Wargo, J
Aird, K
Zhang, RG
Xu, XW
Liu, Q
Speicher, D
Weeraratna, A
AF Kaur, Amanpreet
Marchbank, Katie
Dang, Vanessa
O'Connell, Michael
Webster, Marie
Appleton, Jessica
Cheng, Phil
Valiga, Alexander
Morissette, Rachel
McDonnell, Nazli
Ferrucci, Luigi
Kossenkov, Andrew
Meeth, Katrina
Bosenberg, Marcus
Tang, Hsin-Yao
Yin, Xiangfan
Wood, William, III
Lehrmann, Elin
Becker, Kevin
Flaherty, Keith
Frederick, Dennie
Wargo, Jennifer
Aird, Katherine
Zhang, Rugang
Xu, Xiaowei
Liu, Qin
Speicher, David
Weeraratna, Ashani
TI Aging microenvironment modulates melanoma invasion and metastasis
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT AACR Special Conference on Advances in Melanoma - From Biology to
Therapy
CY SEP 20-23, 2014
CL Philadelphia, PA
SP Amer Assoc Canc Res
C1 [Kaur, Amanpreet; Marchbank, Katie; Dang, Vanessa; O'Connell, Michael; Webster, Marie; Appleton, Jessica; Valiga, Alexander; Kossenkov, Andrew; Tang, Hsin-Yao; Yin, Xiangfan; Aird, Katherine; Zhang, Rugang; Liu, Qin; Speicher, David; Weeraratna, Ashani] Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA.
[Cheng, Phil] Univ Zurich Hosp, CH-8091 Zurich, Switzerland.
[Morissette, Rachel; McDonnell, Nazli; Ferrucci, Luigi; Wood, William, III; Lehrmann, Elin; Becker, Kevin] NIA, NIH, Baltimore, MD 21224 USA.
[Meeth, Katrina; Bosenberg, Marcus] Yale Univ, New Haven, CT USA.
[Flaherty, Keith; Frederick, Dennie; Wargo, Jennifer] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
[Xu, Xiaowei] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD JUL 15
PY 2015
VL 75
SU 14
MA A04
DI 10.1158/1538-7445.MEL2014-A04
PG 2
WC Oncology
SC Oncology
GA DE9QK
UT WOS:000370972700002
ER
PT J
AU Li, YY
Krahn, J
Li, LP
AF Li, Yuanyuan
Krahn, Juno
Li, Leping
TI Assessing the similarity and dissimilarity between primary and
metastatic melanoma using gene expression data
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT AACR Special Conference on Advances in Melanoma - From Biology to
Therapy
CY SEP 20-23, 2014
CL Philadelphia, PA
SP Amer Assoc Canc Res
C1 [Li, Yuanyuan; Krahn, Juno; Li, Leping] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD JUL 15
PY 2015
VL 75
SU 14
MA A17
DI 10.1158/1538-7445.MEL2014-A17
PG 1
WC Oncology
SC Oncology
GA DE9QK
UT WOS:000370972700011
ER
PT J
AU Loftus, S
Cronin, J
Fufa, T
McCallion, A
Crawford, G
Pavan, W
AF Loftus, Stacie
Cronin, Julie
Fufa, Temesgen
McCallion, Andrew
Crawford, Gregory
Pavan, William
TI Epigenetic Cis-regulatory interactions in HIF1a-activated melanocytes
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT AACR Special Conference on Advances in Melanoma - From Biology to
Therapy
CY SEP 20-23, 2014
CL Philadelphia, PA
SP Amer Assoc Canc Res
C1 [Loftus, Stacie; Cronin, Julie; Fufa, Temesgen; Pavan, William] NHGRI, NIH, Bethesda, MD 20892 USA.
[McCallion, Andrew] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med 2, Baltimore, MD USA.
[Crawford, Gregory] Duke Univ, Inst Genome Sci & Policy, Durham, NC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD JUL 15
PY 2015
VL 75
SU 14
MA A23
DI 10.1158/1538-7445.MEL2014-A23
PG 1
WC Oncology
SC Oncology
GA DE9QK
UT WOS:000370972700015
ER
PT J
AU Tucker, MA
AF Tucker, Margaret A.
TI What's new in melanoma etiology?
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT AACR Special Conference on Advances in Melanoma - From Biology to
Therapy
CY SEP 20-23, 2014
CL Philadelphia, PA
SP Amer Assoc Canc Res
C1 [Tucker, Margaret A.] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD JUL 15
PY 2015
VL 75
SU 14
MA IA09
DI 10.1158/1538-7445.MEL2014-IA09
PG 2
WC Oncology
SC Oncology
GA DE9QK
UT WOS:000370972700056
ER
PT J
AU Webster, MR
Xu, M
Kinzler, K
Kaur, A
Appleton, J
O'Connell, MP
Marchbank, K
Valiga, A
Dang, V
Perego, M
Zhang, G
Slipicevic, A
Keeney, F
Lehrmann, E
Wood, W
Becker, K
Kossenkov, AV
Herlyn, M
Murphy, M
Weeraratna, AT
AF Webster, Marie R.
Xu, Mai
Kinzler, Kathryn
Kaur, Amanpreet
Appleton, Jessica
O'Connell, Michael P.
Marchbank, Katie
Valiga, Alexander
Dang, Vanessa
Perego, Michela
Zhang, Gao
Slipicevic, Ana
Keeney, Frederick
Lehrmann, Elin
Wood, William, III
Becker, Kevin
Kossenkov, Andrew V.
Herlyn, Meenhard
Murphy, Maureen
Weeraratna, Ashani T.
TI Wnt5A-expressing melanoma cells show classical markers of senescence
following radiation and therapeutic stress, but retain the ability to
metastasize and proliferate at distant sites
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT AACR Special Conference on Advances in Melanoma - From Biology to
Therapy
CY SEP 20-23, 2014
CL Philadelphia, PA
SP Amer Assoc Canc Res
C1 [Webster, Marie R.; Kaur, Amanpreet; Appleton, Jessica; O'Connell, Michael P.; Marchbank, Katie; Valiga, Alexander; Dang, Vanessa; Perego, Michela; Zhang, Gao; Slipicevic, Ana; Keeney, Frederick; Kossenkov, Andrew V.; Herlyn, Meenhard; Murphy, Maureen; Weeraratna, Ashani T.] Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA.
[Xu, Mai; Kinzler, Kathryn; Lehrmann, Elin; Wood, William, III; Becker, Kevin] NIA, NIH, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD JUL 15
PY 2015
VL 75
SU 14
MA B27
DI 10.1158/1538-7445.MEL2014-B27
PG 1
WC Oncology
SC Oncology
GA DE9QK
UT WOS:000370972700044
ER
PT J
AU Yang, JC
AF Yang, James C.
TI Adoptive T-cell transfer for metastatic melanoma: What are the relevant
antigens?
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT AACR Special Conference on Advances in Melanoma - From Biology to
Therapy
CY SEP 20-23, 2014
CL Philadelphia, PA
SP Amer Assoc Canc Res
C1 [Yang, James 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 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD JUL 15
PY 2015
VL 75
SU 14
MA IA18
DI 10.1158/1538-7445.MEL2014-IA18
PG 1
WC Oncology
SC Oncology
GA DE9QK
UT WOS:000370972700060
ER
PT J
AU Xie, YX
Zhou, B
Lin, MY
Wang, SW
Foust, KD
Sheng, ZH
AF Xie, Yuxiang
Zhou, Bing
Lin, Mei-Yao
Wang, Shiwei
Foust, Kevin D.
Sheng, Zu-Hang
TI Endolysosomal Deficits Augment Mitochondria Pathology in Spinal Motor
Neurons of Asymptomatic fALS Mice
SO NEURON
LA English
DT Article
ID AMYOTROPHIC-LATERAL-SCLEROSIS; LYSOSOMAL STORAGE DISORDERS; LINKED SOD1
MUTANTS; AXONAL-TRANSPORT; TRANSGENIC MICE; MOUSE MODEL; RETROGRADE
TRANSPORT; DELAYS PROGRESSION; LITHIUM-CARBONATE; IN-VIVO
AB One pathological hallmark in ALS motor neurons (MNs) is axonal accumulation of damaged mitochondria. A fundamental question remains: does reduced degradation of those mitochondria by an impaired autophagy-lysosomal system contribute to mitochondrial pathology? We reveal MN-targeted progressive lysosomal deficits accompanied by impaired autophagic degradation beginning at asymptomatic stages in fALS-linked hSOD1(G93A) mice. Lysosomal deficits result in accumulation of autophagic vacuoles engulfing damaged mitochondria along MN axons. Live imaging of spinal MNs from the adult disease mice demonstrates impaired dynein-driven retrograde transport of late endosomes (LEs). Expressing dynein-adaptor snapin reverses transport defects by competing with hSOD1(G93A) for binding dynein, thus rescuing autophagy-lysosomal deficits, enhancing mitochondrial turnover, improving MN survival, and ameliorating the disease phenotype in hSOD1(G93A) mice. Our study provides a new mechanistic link for hSOD1(G93A) mediated impairment of LE transport to autophagy-lysosomal deficits and mitochondrial pathology. Understanding these early pathological events benefits development of new therapeutic interventions for fALS-linked MN degeneration.
C1 [Xie, Yuxiang; Zhou, Bing; Lin, Mei-Yao; Wang, Shiwei; Sheng, Zu-Hang] NINDS, Synapt Funct Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
[Foust, Kevin D.] Ohio State Univ, Dept Neurosci, Columbus, OH 43210 USA.
RP Sheng, ZH (reprint author), NINDS, Synapt Funct Sect, Porter Neurosci Res Ctr, NIH, Room 2B-215,35 Convent Dr, Bethesda, MD 20892 USA.
EM shengz@ninds.nih.gov
FU NINDS, NIH [ZIA NS003029, ZIA NS002946]
FX We thank members of the Z.-H.S. lab for technical assistance and
discussion; S. Cheng, R. Azzam, and V. Crocker at the NINDS Electron
Microscopy Facility for assistance in TEM analysis; and D. Schoenberg
for editing. The work was supported by the Intramural Research Program
of NINDS, NIH ZIA NS003029, and ZIA NS002946 (Z.-H.S.).
NR 52
TC 22
Z9 22
U1 4
U2 13
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
EI 1097-4199
J9 NEURON
JI Neuron
PD JUL 15
PY 2015
VL 87
IS 2
BP 355
EP 370
DI 10.1016/j.neuron.2015.06.026
PG 16
WC Neurosciences
SC Neurosciences & Neurology
GA CR2GJ
UT WOS:000361144200011
PM 26182418
ER
PT J
AU Pickrell, AM
Huang, CH
Kennedy, SR
Ordureau, A
Sideris, DP
Hoekstra, JG
Harper, JW
Youle, RJ
AF Pickrell, Alicia M.
Huang, Chiu-Hui
Kennedy, Scott R.
Ordureau, Alban
Sideris, Dionisia P.
Hoekstra, Jake G.
Harper, J. Wade
Youle, Richard J.
TI Endogenous Parkin Preserves Dopaminergic Substantia Nigral Neurons
following Mitochondrial DNA Mutagenic Stress
SO NEURON
LA English
DT Article
ID COMPLEX-I DEFICIENCY; MTDNA-MUTATOR MICE; ACTIVATE PARKIN;
LOCUS-COERULEUS; MOUSE MODEL; DISEASE; MUTATIONS; UBIQUITIN; PINK1;
PHOSPHORYLATION
AB Parkinson's disease (PD) is a neurodegenerative disease caused by the loss of dopaminergic neurons in the substantia nigra. PARK2 mutations cause early-onset forms of PD. PARK2 encodes an E3 ubiquitin ligase, Parkin, that can selectively translocate to dysfunctional mitochondria to promote their removal by autophagy. However, Parkin knockout (KO) mice do not display signs of neurodegeneration. To assess Parkin function in vivo, we utilized a mouse model that accumulates dysfunctional mitochondria caused by an accelerated generation of mtDNA mutations (Mutator mice). In the absence of Parkin, dopaminergic neurons in Mutator mice degenerated causing an L-DOPA reversible motor deficit. Other neuronal populations were unaffected. Phosphorylated ubiquitin was increased in the brains of Mutator mice, indicating PINK1-Parkin activation. Parkin loss caused mitochondrial dysfunction and affected the pathogenicity but not the levels of mtDNA somatic mutations. A systemic loss of Parkin synergizes with mitochondrial dysfunction causing dopaminergic neuron death modeling PD pathogenic processes.
C1 [Pickrell, Alicia M.; Huang, Chiu-Hui; Sideris, Dionisia P.; Youle, Richard J.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Kennedy, Scott R.; Hoekstra, Jake G.] Univ Washington, Dept Pathol, Seattle, WA 98104 USA.
[Ordureau, Alban; Harper, J. Wade] Harvard Univ, Dept Cell Biol, Sch Med, Boston, MA 02115 USA.
RP Youle, RJ (reprint author), NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
EM youle@helix.nih.gov
RI Ordureau, Alban/C-7558-2012
OI Ordureau, Alban/0000-0002-4924-8520
FU National Institutes of Health Grants NINDS intramural program;
Parkinson's Disease Foundation [PDF-FBS-1216]; NIGMS; Edward R. and Anne
G. Lefler Center; NINDS [R37NS083524]; Genetic Approaches to Aging
Training Grant [NIA T32-AG000057]
FX This work was supported in part by the National Institutes of Health
Grants NINDS intramural program (R.J.Y.), Parkinson's Disease Foundation
Fellowship PDF-FBS-1216 and intramural NIGMS Postdoctoral Research
Associate Fellowship (PRAT) (A.M.P.), Edward R. and Anne G. Lefler
Center Postdoctoral Fellowship (A.O.), NINDS Grant R37NS083524 (J.W.H.),
and the Genetic Approaches to Aging Training Grant NIA T32-AG000057
(S.R.K.).
NR 62
TC 31
Z9 31
U1 2
U2 10
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
EI 1097-4199
J9 NEURON
JI Neuron
PD JUL 15
PY 2015
VL 87
IS 2
BP 371
EP 381
DI 10.1016/j.neuron.2015.06.034
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA CR2GJ
UT WOS:000361144200012
PM 26182419
ER
PT J
AU Liu, YH
Zhou, RK
Sulman, EP
Scheurer, ME
Boehling, N
Armstrong, GN
Tsavachidis, S
Liang, FW
Etzel, CJ
Conrad, CA
Gilbert, MR
Armstrong, TS
Bondy, ML
Wefel, JS
AF Liu, Yanhong
Zhou, Renke
Sulman, Erik P.
Scheurer, Michael E.
Boehling, Nicholas
Armstrong, Georgina N.
Tsavachidis, Spiridon
Liang, Fu-Wen
Etzel, Carol J.
Conrad, Charles A.
Gilbert, Mark R.
Armstrong, Terri S.
Bondy, Melissa L.
Wefel, Jeffrey S.
TI Genetic Modulation of Neurocognitive Function in Glioma Patients
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID NEWLY-DIAGNOSED GLIOBLASTOMA; HIGH-GRADE GLIOMA; COGNITIVE PERFORMANCE;
BRAIN-TUMORS; BREAST-CANCER; APOE; SUSCEPTIBILITY; POLYMORPHISMS;
ASSOCIATION; SURVIVAL
AB Purpose: Accumulating evidence supports the contention that genetic variation is associated with neurocognitive function in healthy individuals and increased risk for neurocognitive decline in a variety of patient populations, including cancer patients. However, this has rarely been studied in glioma patients.
Experimental Design: To identify the effect of genetic variants on neurocognitive function, we examined the relationship between the genotype frequencies of 10,967 single-nucleotide polymorphisms in 580 genes related to five pathways (inflammation, DNA repair, metabolism, cognitive, and telomerase) and neurocognitive function in 233 newly diagnosed glioma patients before surgical resection. Four neuropsychologic tests that measured memory (Hopkins Verbal Learning Test-Revised), processing speed (Trail Making Test A), and executive function (Trail Making Test B, Controlled Oral Word Association) were examined.
Results: Eighteen polymorphisms were associated with processing speed and 12 polymorphisms with executive function. For processing speed, the strongest signals were in IRS1 rs6725330 in the inflammation pathway (P = 2.5 x 10(-10)), ERCC4 rs1573638 in the DNA repair pathway (P = 3.4 x 10(-7)), and ABCC1 rs8187858 in metabolism pathway (P = 6.6 x 10(-7)). For executive function, the strongest associations were in NOS1 rs11611788 (P = 1.8 x 10(-8)) and IL16 rs1912124 (P = 6.0 x 10(-7)) in the inflammation pathway, and POLE rs5744761 (P = 6.0 x 10(-7)) in the DNA repair pathway. Joint effect analysis found significant gene polymorphism-dosage effects for processing speed (P-trend = 9.4 x 10(-16)) and executive function (P-trend = 6.6 x 10(-15)).
Conclusions: Polymorphisms in inflammation, DNA repair, and metabolism pathways are associated with neurocognitive function in glioma patients and may affect clinical outcomes. (C) 2015 AACR.
C1 [Liu, Yanhong; Zhou, Renke; Scheurer, Michael E.; Armstrong, Georgina N.; Tsavachidis, Spiridon; Bondy, Melissa L.] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA.
[Liu, Yanhong; Scheurer, Michael E.; Bondy, Melissa L.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
[Sulman, Erik P.; Boehling, Nicholas] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA.
[Liang, Fu-Wen] Natl Cheng Kung Univ, Coll Med, Inst Publ Hlth, Tainan 70101, Taiwan.
[Etzel, Carol J.] Corrona LLC, Biostat, Southborough, MA USA.
[Conrad, Charles A.; Wefel, Jeffrey S.] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA.
[Gilbert, Mark R.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
[Armstrong, Terri S.] Univ Texas Hlth Sci Ctr Houston, Sch Nursing, Houston, TX 77030 USA.
RP Wefel, JS (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Sect Neuropsychol, 1515 Holcombe Blvd,Unit 431, Houston, TX 77030 USA.
EM mbondy@bcm.edu; jwefel@mdanderson.org
RI Gilbert, Mark/J-7494-2016
OI Gilbert, Mark/0000-0003-2556-9722
FU NIH [R01NR014195, R01CA119215, R01CA070917, R01CA139020, K07CA131505];
American Brain Tumor Association; National Brain Tumor Society
FX Research reported in this article was supported by the NIH grants
R01NR014195, R01CA119215, R01CA070917, R01CA139020, and K07CA131505.
Additional support was provided by the American Brain Tumor Association
and The National Brain Tumor Society.
NR 48
TC 2
Z9 2
U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JUL 15
PY 2015
VL 21
IS 14
BP 3340
EP 3346
DI 10.1158/1078-0432.CCR-15-0168
PG 7
WC Oncology
SC Oncology
GA CO7FC
UT WOS:000359324000027
PM 25904748
ER
PT J
AU Ridnour, LA
Cheng, RYS
Weiss, JM
Kaur, S
Soto-Pantoja, DR
Basudhar, D
Heinecke, JL
Stewart, CA
DeGraff, W
Sowers, AL
Thetford, A
Kesarwala, AH
Roberts, DD
Young, HA
Mitchell, JB
Trinchieri, G
Wiltrout, RH
Wink, DA
AF Ridnour, Lisa A.
Cheng, Robert Y. S.
Weiss, Jonathan M.
Kaur, Sukhbir
Soto-Pantoja, David R.
Basudhar, Debashree
Heinecke, Julie L.
Stewart, C. Andrew
DeGraff, William
Sowers, Anastasia L.
Thetford, Angela
Kesarwala, Aparna H.
Roberts, David D.
Young, Howard A.
Mitchell, James B.
Trinchieri, Giorgio
Wiltrout, Robert H.
Wink, David A.
TI NOS Inhibition Modulates Immune Polarization and Improves
Radiation-Induced Tumor Growth Delay
SO CANCER RESEARCH
LA English
DT Article
ID NITRIC-OXIDE SYNTHASE; NEGATIVE BREAST-CANCER; CELL DIFFERENTIATION;
IONIZING-RADIATION; POOR SURVIVAL; WOUND REPAIR; T-CELLS; ANGIOGENESIS;
THERAPY; THROMBOSPONDIN-1
AB Nitric oxide synthases (NOS) are important mediators of progrowth signaling in tumor cells, as they regulate angiogenesis, immune response, and immune-mediated wound healing. Ionizing radiation (IR) is also an immune modulator and inducer of wound response. We hypothesized that radiation therapeutic efficacy could be improved by targeting NOS following tumor irradiation. Herein, we show enhanced radiation-induced (10 Gy) tumor growth delay in a syngeneic model (C3H) but not immunosuppressed (Nu/Nu) squamous cell carcinoma tumor-bearing mice treated post-IR with the constitutive NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME). These results suggest a requirement of T cells for improved radiation tumor response. In support of this observation, tumor irradiation induced a rapid increase in the immunosuppressive Th2 cytokine IL10, which was abated by post-IR administration of L-NAME. In vivo suppres-sion of IL10 using an antisense IL10 morpholino also extended the tumor growth delay induced by radiation in a manner similar to L-NAME. Further examination of this mechanism in cultured Jurkat T cells revealed L-NAME suppression of IR-induced IL10 expression, which reaccumulated in the presence of exogenous NO donor. In addition to L-NAME, the guanylyl cyclase inhibitors ODQ and thrombospondin-1 also abated IR-induced IL10 expression in Jurkat T cells and ANA-1 macrophages, which further suggests that the immunosuppressive effects involve eNOS. Moreover, cytotoxic Th1 cytokines, including IL2, IL12p40, and IFN gamma, as well as activated CD8(+) T cells were elevated in tumors receiving post-IR L-NAME. Together, these results suggest that post-IR NOS inhibition improves radiation tumor response via Th1 immune polarization within the tumor microenvironment. (C) 2015 AACR.
C1 [Ridnour, Lisa A.; Cheng, Robert Y. S.; Basudhar, Debashree; Heinecke, Julie L.; DeGraff, William; Sowers, Anastasia L.; Thetford, Angela; Mitchell, James B.; Wink, David A.] NCI, Radiat Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Weiss, Jonathan M.; Stewart, C. Andrew; Young, Howard A.; Trinchieri, Giorgio; Wiltrout, Robert H.] NCI, Canc Inflammat Program, Ctr Canc Res, Frederick, MD 21701 USA.
[Kaur, Sukhbir; Soto-Pantoja, David R.; Roberts, David D.] NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Kesarwala, Aparna H.] NCI, Radiat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Ridnour, LA (reprint author), NCI, NIH, Bldg 10,B3B35,10 Ctr Dr, Bethesda, MD 20892 USA.
EM ridnourl@mail.nih.gov
RI Roberts, David/A-9699-2008
OI Roberts, David/0000-0002-2481-2981
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute; Center for Cancer Research
FX This researchwas supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, and Center for
Cancer Research (D.A. Wink, D.D. Roberts, H.A. Young, J.B. Mitchell, G.
Trinchieri, and R.H. Wiltrout).
NR 60
TC 6
Z9 6
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 JUL 15
PY 2015
VL 75
IS 14
BP 2788
EP 2799
DI 10.1158/0008-5472.CAN-14-3011
PG 12
WC Oncology
SC Oncology
GA CO7EK
UT WOS:000359322100004
PM 25990221
ER
PT J
AU Doci, CL
Mikelis, CM
Lionakis, MS
Molinolo, AA
Gutkind, JS
AF Doci, Colleen L.
Mikelis, Constantinos M.
Lionakis, Michail S.
Molinolo, Alfredo A.
Gutkind, J. Silvio
TI Genetic Identification of SEMA3F as an Antilymphangiogenic Metastasis
Suppressor Gene in Head and Neck Squamous Carcinoma
SO CANCER RESEARCH
LA English
DT Article
ID GROWTH-FACTOR-C; LYMPH-NODE METASTASES; CELL CARCINOMA; VEGF-C; TUMOR
ANGIOGENESIS; VESSEL DEVELOPMENT; ENDOTHELIAL-CELLS; AXON GUIDANCE;
CANCER; LYMPHANGIOGENESIS
AB Head and neck squamous cell carcinomas (HNSCC) often metastasize to locoregional lymph nodes, and lymph node involvement represents one of the most important prognostic factors of poor clinical outcome. HNSCCs are remarkably lymphangiogenic and represent a clear example of a cancer that utilizes the lymphatic vasculature for malignant dissemination; however, the molecular mechanisms underlying lymphangiogenesis in HNSCC is still poorly understood. Of interest, we found that an axon guidance molecule, Semaphorin 3F (SEMA3F), is among the top 1% underexpressed genes in HNSCC, and that genomic loss of SEMA3F correlates with increased metastasis and decreased survival. SEMA3F acts on its coreceptors, plexins and neuropilins, among which neuropilin-2 (NRP2) is highly expressed in lymphatic endothelial cells (LEC) but not in oral epithelium and most HNSCCs. We show that recombinant SEMA3F promotes LEC collapse and potently inhibits lymphangiogenesis in vivo. By reconstituting all possible plexin and neuropilin combinations, we found that SEMA3F acts through multiple receptors, but predominantly requires NRP2 to signal in LECs. Using orthotopic HNSCC metastasis mouse models, we provide direct evidence that SEMA3F re-expression diminishes lymphangiogenesis and lymph node metastasis. Furthermore, analysis of a large tissue collection revealed that SEMA3F is progressively lost during HNSCC progression, concomitant with increased tumor lymphangiogenesis. SEMA3F is localized to 3p21, an early and frequently deleted locus in HNSCC and many other prevalent human malignancies. Thus, SEMA3F may represent an antilymphangiogenicmetastasis suppressor gene widely lost during cancer progression, hence serving as a prognostic biomarker and an attractive target for therapeutic intervention to halt metastasis. (C)2015 AACR.
C1 [Doci, Colleen L.; Mikelis, Constantinos M.; Molinolo, Alfredo A.; Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
[Lionakis, Michail S.] NIAID, Fungal Pathogenesis Unit, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Gutkind, JS (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr,Bldg 30,Rm 320, Bethesda, MD 20892 USA.
EM sg39v@nih.gov
FU Intramural Research Program of the National Institute of Dental and
Craniofacial Research; National Institute of Allergy & Infectious
Diseases, NIH [Z01DE00558-23, Z01DE00551-23]
FX This research was supported by the Intramural Research Program of the
National Institute of Dental and Craniofacial Research, and in part by
the National Institute of Allergy & Infectious Diseases, NIH
(Z01DE00558-23 and Z01DE00551-23).
NR 50
TC 8
Z9 8
U1 1
U2 2
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 JUL 15
PY 2015
VL 75
IS 14
BP 2937
EP 2948
DI 10.1158/0008-5472.CAN-14-3121
PG 12
WC Oncology
SC Oncology
GA CO7EK
UT WOS:000359322100018
PM 25952650
ER
PT J
AU Lee, JA
Shinn, P
Jaken, S
Oliver, S
Willard, FS
Heidler, S
Peery, RB
Oler, J
Chu, SY
Southall, N
Dexheimer, TS
Smallwood, J
Huang, R
Guha, R
Jadhav, A
Cox, K
Austin, CP
Simeonov, A
Sittampalam, GS
Husain, S
Franklin, N
Wild, DJ
Yang, JJ
Sutherland, JJ
Thomas, CJ
AF Lee, Jonathan A.
Shinn, Paul
Jaken, Susan
Oliver, Sarah
Willard, Francis S.
Heidler, Steven
Peery, Robert B.
Oler, Jennifer
Chu, Shaoyou
Southall, Noel
Dexheimer, Thomas S.
Smallwood, Jeffrey
Huang, Ruili
Guha, Rajarshi
Jadhav, Ajit
Cox, Karen
Austin, Christopher P.
Simeonov, Anton
Sittampalam, G. Sitta
Husain, Saba
Franklin, Natalie
Wild, David J.
Yang, Jeremy J.
Sutherland, Jeffrey J.
Thomas, Craig J.
TI Novel Phenotypic Outcomes Identified for a Public Collection of Approved
Drugs from a Publicly Accessible Panel of Assays
SO PLOS ONE
LA English
DT Article
ID FATTY-ACID SYNTHASE; ANTI-ATHEROSCLEROTIC AGENTS;
FUNCTIONAL-CHARACTERIZATION; DIHYDROFOLATE-REDUCTASE; INSULIN
SENSITIVITY; ANTITUMOR-ACTIVITY; COLORECTAL-CANCER; MOLECULAR TARGETS;
OXIDATIVE STRESS; CETABEN SODIUM
AB Phenotypic assays have a proven track record for generating leads that become first-in-class therapies. Whole cell assays that inform on a phenotype or mechanism also possess great potential in drug repositioning studies by illuminating new activities for the existing pharmacopeia. The National Center for Advancing Translational Sciences (NCATS) pharmaceutical collection (NPC) is the largest reported collection of approved small molecule therapeutics that is available for screening in a high-throughput setting. Via a wide-ranging collaborative effort, this library was analyzed in the Open Innovation Drug Discovery (OIDD) phenotypic assay modules publicly offered by Lilly. The results of these tests are publically available online at www.ncats.nih.gov/expertise/preclinical/pd2 and via the PubChem Database (https://pubchem.ncbi.nlm.nih.gov/) (AID 1117321). Phenotypic outcomes for numerous drugs were confirmed, including sulfonylureas as insulin secretagogues and the anti-angiogenesis actions of multikinase inhibitors sorafenib, axitinib and pazopanib. Several novel outcomes were also noted including the Wnt potentiating activities of rotenone and the antifolate class of drugs, and the anti-angiogenic activity of cetaben.
C1 [Lee, Jonathan A.; Jaken, Susan; Oliver, Sarah; Willard, Francis S.; Heidler, Steven; Peery, Robert B.; Oler, Jennifer; Chu, Shaoyou; Smallwood, Jeffrey; Cox, Karen; Husain, Saba; Franklin, Natalie; Sutherland, Jeffrey J.] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA.
[Shinn, Paul; Southall, Noel; Dexheimer, Thomas S.; Huang, Ruili; Guha, Rajarshi; Jadhav, Ajit; Austin, Christopher P.; Simeonov, Anton; Sittampalam, G. Sitta; Thomas, Craig J.] NIH, Div Preclin Innovat, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
[Wild, David J.; Yang, Jeremy J.] Indiana Univ, Sch Informat & Comp, Bloomington, IN USA.
RP Sutherland, JJ (reprint author), Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA.
EM sutherland_jeffrey_james@lilly.com; craigt@mail.nih.gov
RI Southall, Noel/H-8991-2012
OI Southall, Noel/0000-0003-4500-880X
FU Intramural Program of NCATS; Lilly Research Laboratories
FX This study was supported by the Intramural Program of NCATS and the
Lilly Research Laboratories. The funders of this study provided support
in the form of salaries for all authors, but did not have any additional
role in the study design, data collection and analysis, decision to
publish, or preparation of the manuscript. The specific roles of these
authors are articulated in the 'author contributions' section.
NR 75
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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 JUL 15
PY 2015
VL 10
IS 7
AR e0130796
DI 10.1371/journal.pone.0130796
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN1RL
UT WOS:000358197600029
PM 26177200
ER
PT J
AU Sek, AC
Xie, ZH
Terai, K
Long, LM
Nelson, C
Dudek, AZ
Druey, KM
AF Sek, Albert C.
Xie, Zhihui
Terai, Kaoru
Long, Lauren M.
Nelson, Celeste
Dudek, Arkadiusz Z.
Druey, Kirk M.
TI Endothelial Expression of Endothelin Receptor A in the Systemic
Capillary Leak Syndrome
SO PLOS ONE
LA English
DT Article
ID SYNDROME CLARKSON DISEASE; VON-WILLEBRAND-FACTOR; GENE-THERAPY; CELLS;
BLOOD; PERMEABILITY; ESTABLISHMENT; HYPERTENSION; EDEMA
AB Idiopathic systemic capillary leak syndrome (SCLS) is a rare and potentially fatal vascular disorder characterized by reversible bouts of hypotension and edema resulting from fluid and solute escape into soft tissues. Although spikes in permeability-inducing factors have been linked to acute SCLS flares, whether or not they act on an inherently dysfunctional endothelium is unknown. To assess the contribution of endothelial-intrinsic mechanisms in SCLS, we derived blood-outgrowth endothelial cells (BOEC) from patients and healthy controls and examined gene expression patterns. Ednra, encoding Endothelin receptor A (ETA)-the target of Endothelin 1 (ET-1)-was significantly increased in SCLS BOEC compared to healthy controls. Although vasoconstriction mediated by ET-1 through ETA activation on vascular smooth muscle cells has been well characterized, the expression and function of ETA receptors in endothelial cells (ECs) has not been described. To determine the role of ETA and its ligand ET-1 in SCLS, if any, we examined ET-1 levels in SCLS sera and functional effects of endothelial ETA expression. ETA overexpression in EAhy926 endothelioma cells led to ET-1-induced hyper-permeability through canonical mechanisms. Serum ET-1 levels were elevated in acute SCLS sera compared to remission and healthy control sera, suggesting a possible role for ET-1 and ETA in SCLS pathogenesis. However, although ET-1 alone did not induce hyper-permeability of patient-derived BOEC, an SCLS-related mediator (CXCL10) increased Edrna quantities in BOEC, suggesting a link between SCLS and endothelial ETA expression. These results demonstrate that ET-1 triggers classical mechanisms of vascular barrier dysfunction in ECs through ETA. Further studies of the ET-1-ETA axis in SCLS and in more common plasma leakage syndromes including sepsis and filovirus infection would advance our understanding of vascular integrity mechanisms and potentially uncover new treatment strategies.
C1 [Sek, Albert C.; Xie, Zhihui; Long, Lauren M.; Nelson, Celeste; Druey, Kirk M.] NIAID, NIH, Bethesda, MD 20892 USA.
[Terai, Kaoru; Dudek, Arkadiusz Z.] Univ Illinois, Dept Med, Div Hematol Oncol, Chicago, IL USA.
RP Druey, KM (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM kdruey@niaid.nih.gov
OI Sek, Albert/0000-0002-8170-3749
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health [AI001083]
FX This study was funded by the Intramural Research Program of the National
Institute of Allergy and Infectious Diseases, National Institutes of
Health (AI001083 to KMD) (http://www.niaid.nih.gov/Pages/default.aspx.)
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 37
TC 2
Z9 2
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 JUL 15
PY 2015
VL 10
IS 7
AR e0133266
DI 10.1371/journal.pone.0133266
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN1RL
UT WOS:000358197600236
PM 26176954
ER
PT J
AU Ashtari, M
Zhang, H
Cook, PA
Cyckowski, LL
Shindler, KS
Marshall, KA
Aravand, P
Vossough, A
Gee, JC
Maguire, AM
Baker, CI
Bennett, J
AF Ashtari, Manzar
Zhang, Hui
Cook, Philip A.
Cyckowski, Laura L.
Shindler, Kenneth S.
Marshall, Kathleen A.
Aravand, Puya
Vossough, Arastoo
Gee, James C.
Maguire, Albert M.
Baker, Chris I.
Bennett, Jean
TI Plasticity of the human visual system after retinal gene therapy in
patients with Leber's congenital amaurosis
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID DIFFUSION TENSOR TRACTOGRAPHY; WHITE-MATTER; MONOCULAR DEPRIVATION;
STRIATE CORTEX; IN-VIVO; KITTENS; BLIND; MOUSE; REVERSAL; BRAIN
AB Much of our knowledge of the mechanisms underlying plasticity in the visual cortex in response to visual impairment, vision restoration, and environmental interactions comes from animal studies. We evaluated human brain plasticity in a group of patients with Leber's congenital amaurosis (LCA), who regained vision through gene therapy. Using non-invasive multimodal neuroimaging methods, we demonstrated that reversing blindness with gene therapy promoted long-term structural plasticity in the visual pathways emanating from the treated retina of LCA patients. The data revealed improvements and normalization along the visual fibers corresponding to the site of retinal injection of the gene therapy vector carrying the therapeutic gene in the treated eye compared to the visual pathway for the untreated eye of LCA patients. After gene therapy, the primary visual pathways (for example, geniculostriate fibers) in the treated retina were similar to those of sighted control subjects, whereas the primary visual pathways of the untreated retina continued to deteriorate. Our results suggest that visual experience, enhanced by gene therapy, may be responsible for the reorganization and maturation of synaptic connectivity in the visual pathways of the treated eye in LCA patients. The interactions between the eye and the brain enabled improved and sustained long-term visual function in patients with LCA after gene therapy.
C1 [Ashtari, Manzar; Shindler, Kenneth S.; Aravand, Puya; Maguire, Albert M.; Bennett, Jean] Univ Penn, Perelman Sch Med, Ctr Adv Retinal & Ocular Therapeut, Philadelphia, PA 19104 USA.
[Ashtari, Manzar; Shindler, Kenneth S.; Aravand, Puya; Maguire, Albert M.; Bennett, Jean] Univ Penn, Dept Ophthalmol, Scheie Eye Inst, FM Kirby Ctr Mol Ophthalmol, Philadelphia, PA 19014 USA.
[Zhang, Hui] UCL, Dept Comp Sci, London WC1E 6BT, England.
[Zhang, Hui] UCL, Ctr Med Image Comp, London WC1E 6BT, England.
[Cook, Philip A.; Gee, James C.] Univ Penn, Dept Radiol, Penn Image Comp & Sci Lab, Philadelphia, PA 19104 USA.
[Cyckowski, Laura L.; Vossough, Arastoo] Childrens Hosp Philadelphia, Dept Radiol, Philadelphia, PA 19014 USA.
[Marshall, Kathleen A.; Maguire, Albert M.; Bennett, Jean] Childrens Hosp Philadelphia, Ctr Cellular & Mol Therapeut, Philadelphia, PA 19014 USA.
[Baker, Chris I.] NIH, Lab Brain & Cognit, Bethesda, MD 20892 USA.
RP Ashtari, M (reprint author), Univ Penn, Perelman Sch Med, Ctr Adv Retinal & Ocular Therapeut, 309 Stellar Chance Labs,422 Curie Blvd, Philadelphia, PA 19104 USA.
EM ashtari@mail.med.upenn.edu
OI Baker, Chris/0000-0001-6861-8964
FU NIH [R21EY020662, 8DP1EY023177, 1R24EY019861, P30 EY001583]; Foundation
Fighting Blindness-sponsored CHOP-PENN (The Children's Hospital of
Philadelphia-Penn Medicine) Pediatric Center for Retinal Degenerations
[C-GT-0913-06280UPA03]; Transdisciplinary Awards Program in
Translational Medicine and Therapeutics (TAPITMAT) grants; University of
Pennsylvania, Research to Prevent Blindness; F.M. Kirby Foundation;
Intramural Research Program of the National Institute of Mental Health
FX Funding was provided by the NIH R21EY020662, Foundation Fighting
Blindness-sponsored CHOP-PENN (The Children's Hospital of
Philadelphia-Penn Medicine) Pediatric Center for Retinal Degenerations,
C-GT-0913-06280UPA03, NIH 8DP1EY023177, NIH 1R24EY019861, NIH P30
EY001583, Transdisciplinary Awards Program in Translational Medicine and
Therapeutics (TAPITMAT) grants, University of Pennsylvania, Research to
Prevent Blindness, and the F.M. Kirby Foundation. C.I.B. is supported by
the Intramural Research Program of the National Institute of Mental
Health.
NR 56
TC 9
Z9 9
U1 4
U2 20
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
EI 1946-6242
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD JUL 15
PY 2015
VL 7
IS 296
AR 296ra110
DI 10.1126/scitranslmed.aaa8791
PG 13
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA CN9AQ
UT WOS:000358738400003
PM 26180100
ER
PT J
AU Phillips, MA
Lotharius, J
Marsh, K
White, J
Dayan, A
White, KL
Njoroge, JW
El Mazouni, F
Lao, YB
Kokkonda, S
Tomchick, DR
Deng, XY
Laird, T
Bhatia, SN
March, S
Ng, CL
Fidock, DA
Wittlin, S
Lafuente-Monasterio, M
Benito, FJG
Alonso, LMS
Martinez, MS
Jimenez-Diaz, MB
Bazaga, SF
Angulo-Barturen, I
Haselden, JN
Louttit, J
Cui, Y
Sridhar, A
Zeeman, AM
Kocken, C
Sauerwein, R
Dechering, K
Avery, VM
Duffy, S
Delves, M
Sinden, R
Ruecker, A
Wickham, KS
Rochford, R
Gahagen, J
Iyer, L
Riccio, E
Mirsalis, J
Bathhurst, I
Rueckle, T
Ding, X
Campo, B
Leroy, D
Rogers, MJ
Rathod, PK
Burrows, JN
Charman, SA
AF Phillips, Margaret A.
Lotharius, Julie
Marsh, Kennan
White, John
Dayan, Anthony
White, Karen L.
Njoroge, Jacqueline W.
El Mazouni, Farah
Lao, Yanbin
Kokkonda, Sreekanth
Tomchick, Diana R.
Deng, Xiaoyi
Laird, Trevor
Bhatia, Sangeeta N.
March, Sandra
Ng, Caroline L.
Fidock, David A.
Wittlin, Sergio
Lafuente-Monasterio, Maria
Gamo Benito, Francisco Javier
Sanz Alonso, Laura Maria
Santos Martinez, Maria
Belen Jimenez-Diaz, Maria
Ferrer Bazaga, Santiago
Angulo-Barturen, Inigo
Haselden, John N.
Louttit, James
Cui, Yi
Sridhar, Arun
Zeeman, Anna-Marie
Kocken, Clemens
Sauerwein, Robert
Dechering, Koen
Avery, Vicky M.
Duffy, Sandra
Delves, Michael
Sinden, Robert
Ruecker, Andrea
Wickham, Kristina S.
Rochford, Rosemary
Gahagen, Janet
Iyer, Lalitha
Riccio, Ed
Mirsalis, Jon
Bathhurst, Ian
Rueckle, Thomas
Ding, Xavier
Campo, Brice
Leroy, Didier
Rogers, M. John
Rathod, Pradipsinh K.
Burrows, Jeremy N.
Charman, Susan A.
TI A long-duration dihydroorotate dehydrogenase inhibitor (DSM265) for
prevention and treatment of malaria
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID PLASMODIUM-FALCIPARUM; IN-VITRO; CLINICAL CANDIDATE; LEAD OPTIMIZATION;
DRUG DEVELOPMENT; RESISTANCE; POTENT; ASSAY; IDENTIFICATION; SAFETY
AB Malaria is one of the most significant causes of childhood mortality, but disease control efforts are threatened by resistance of the Plasmodium parasite to current therapies. Continued progress in combating malaria requires development of new, easy to administer drug combinations with broad-ranging activity against all manifestations of the disease. DSM265, a triazolopyrimidine-based inhibitor of the pyrimidine biosynthetic enzyme dihydroorotate dehydrogenase (DHODH), is the first DHODH inhibitor to reach clinical development for treatment of malaria. We describe studies profiling the biological activity, pharmacological and pharmacokinetic properties, and safety of DSM265, which supported its advancement to human trials. DSM265 is highly selective toward DHODH of the malaria parasite Plasmodium, efficacious against both blood and liver stages of P. falciparum, and active against drugresistant parasite isolates. Favorable pharmacokinetic properties of DSM265 are predicted to provide therapeutic concentrations for more than 8 days after a single oral dose in the range of 200 to 400 mg. DSM265 was well tolerated in repeat-dose and cardiovascular safety studies in mice and dogs, was not mutagenic, and was inactive against panels of human enzymes/receptors. The excellent safety profile, blood-and liver-stage activity, and predicted long half-life in humans position DSM265 as a new potential drug combination partner for either single-dose treatment or once-weekly chemoprevention. DSM265 has advantages over current treatment options that are dosed daily or are inactive against the parasite liver stage.
C1 [Phillips, Margaret A.; Njoroge, Jacqueline W.; El Mazouni, Farah; Deng, Xiaoyi] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA.
[Lotharius, Julie; Dayan, Anthony; Laird, Trevor; Bathhurst, Ian; Rueckle, Thomas; Ding, Xavier; Campo, Brice; Leroy, Didier; Burrows, Jeremy N.] Med Malaria Venture, CH-1215 Geneva, Switzerland.
[Marsh, Kennan; Lao, Yanbin] Abbvie, N Chicago, IL 60064 USA.
[White, John; Kokkonda, Sreekanth; Rathod, Pradipsinh K.] Univ Washington, Dept Chem, Seattle, WA 98195 USA.
[White, John; Kokkonda, Sreekanth; Rathod, Pradipsinh K.] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA.
[White, Karen L.; Charman, Susan A.] Monash Univ, Monash Inst Pharmaceut Sci, Ctr Drug Candidate Optimisat, Parkville, Vic 3052, Australia.
[Tomchick, Diana R.] Univ Texas SW Med Ctr Dallas, Dept Biophys, Dallas, TX 75390 USA.
[Bhatia, Sangeeta N.; March, Sandra] MIT, Hlth Sci & Technol, Inst Med Engn & Sci, Cambridge, MA 02139 USA.
[Ng, Caroline L.; Fidock, David A.] Columbia Univ, Med Ctr, Dept Microbiol & Immunol, New York, NY 10032 USA.
[Fidock, David A.] Columbia Univ, Med Ctr, Dept Med, Div Infect Dis, New York, NY 10032 USA.
[Wittlin, Sergio] Swiss Trop & Publ Hlth Inst, CH-4002 Basel, Switzerland.
[Wittlin, Sergio] Univ Basel, CH-4003 Basel, Switzerland.
[Lafuente-Monasterio, Maria; Gamo Benito, Francisco Javier; Sanz Alonso, Laura Maria; Santos Martinez, Maria; Belen Jimenez-Diaz, Maria; Ferrer Bazaga, Santiago; Angulo-Barturen, Inigo; Haselden, John N.] GlaxoSmithKline GSK, Madrid 28760, Spain.
[Louttit, James; Cui, Yi; Sridhar, Arun] GSK, Ware SG12 0DP, Herts, England.
[Zeeman, Anna-Marie; Kocken, Clemens] Biomed Primate Res Ctr, NL-2280 GH Rijswijk, Netherlands.
[Sauerwein, Robert; Dechering, Koen] TropIQ Hlth Sci, NL-6525 GA Nijmegen, Netherlands.
[Avery, Vicky M.; Duffy, Sandra] Griffith Univ, Eskitis Inst Drug Discovery, Discovery Biol, Nathan, Qld 4111, Australia.
[Delves, Michael; Sinden, Robert; Ruecker, Andrea] Univ London Imperial Coll Sci Technol & Med, London SW7 2AY, England.
[Wickham, Kristina S.; Rochford, Rosemary] SUNY Upstate Med Univ, Syracuse, NY 13210 USA.
[Gahagen, Janet; Iyer, Lalitha; Riccio, Ed; Mirsalis, Jon] SRI Int, Menlo Pk, CA 94025 USA.
[Rogers, M. John] NIAID, Bethesda, MD 20892 USA.
RP Phillips, MA (reprint author), Univ Texas SW Med Ctr Dallas, Dept Pharmacol, 6001 Forest Pk Blvd, Dallas, TX 75390 USA.
EM margaret.phillips@utsouthwestern.edu; susan.charman@monash.edu
RI Sauerwein, Robert/C-8519-2013; Avery, Vicky/A-5449-2010; Charman,
Susan/E-2221-2011; duffy, sandra/B-8479-2017;
OI Charman, Susan/0000-0003-1753-8213; duffy, sandra/0000-0002-2814-1193;
Tomchick, Diana/0000-0002-7529-4643
FU U.S. NIH [U01AI075594, R01AI103947]; Medicines for Malaria Venture
(MMV); Welch Foundation [I-1257]; Beatrice and Miguel Elias
Distinguished Chair in Biomedical Science; Medical Science and
Education; MMV; Wellcome Trust [WT078285]
FX This work was supported by funds from the U.S. NIH grants U01AI075594
(to I.B., M.A.P., P.K.R., and S.A.C.) and R01AI103947 (to M.A.P. and
P.K.R.) and from Medicines for Malaria Venture (MMV). M.A.P.
acknowledges the support of the Welch Foundation (I-1257). M.A.P. holds
the Beatrice and Miguel Elias Distinguished Chair in Biomedical Science
and the Carolyn R. Bacon Professorship in Medical Science and Education.
Biomedical Primate Research Centre (BBRC) (A. M.-Z. and C.K.) and
Columbia University (C.L.N. and D.A.F.) were supported by funding from
the MMV. BBRC was also supported by a translational research grant
(WT078285) from the Wellcome Trust.
NR 66
TC 39
Z9 39
U1 2
U2 29
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 JUL 15
PY 2015
VL 7
IS 296
AR 296ra111
DI 10.1126/scitranslmed.aaa6645
PG 12
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA CN9AQ
UT WOS:000358738400004
PM 26180101
ER
PT J
AU Prentice, HA
Tomaras, GD
Geraghty, DE
Apps, R
Fong, YY
Ehrenberg, PK
Rolland, M
Kijak, GH
Krebs, SJ
Nelson, W
DeCamp, A
Shen, XY
Yates, NL
Zolla-Pazner, S
Nitayaphan, S
Rerks-Ngarm, S
Kaewkungwal, J
Pitisuttithum, P
Ferrari, G
McElrath, MJ
Montefiori, DC
Bailer, RT
Koup, RA
O'Connell, RJ
Robb, ML
Michael, NL
Gilbert, PB
Kim, JH
Thomas, R
AF Prentice, Heather A.
Tomaras, Georgia D.
Geraghty, Daniel E.
Apps, Richard
Fong, Youyi
Ehrenberg, Philip K.
Rolland, Morgane
Kijak, Gustavo H.
Krebs, Shelly J.
Nelson, Wyatt
DeCamp, Allan
Shen, Xiaoying
Yates, Nicole L.
Zolla-Pazner, Susan
Nitayaphan, Sorachai
Rerks-Ngarm, Supachai
Kaewkungwal, Jaranit
Pitisuttithum, Punnee
Ferrari, Guido
McElrath, M. Juliana
Montefiori, David C.
Bailer, Robert T.
Koup, Richard A.
O'Connell, Robert J.
Robb, Merlin L.
Michael, Nelson L.
Gilbert, Peter B.
Kim, Jerome H.
Thomas, Rasmi
TI HLA class II genes modulate vaccine-induced antibody responses to affect
HIV-1 acquisition
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID T-CELL RESPONSES; EFFICACY TRIAL; POTENT NEUTRALIZATION; ENVELOPE
GLYCOPROTEIN; ALVAC-HIV; GP120; ASSOCIATION; ANTIGEN; BINDING;
SUSCEPTIBILITY
AB In the RV144 vaccine trial, two antibody responses were found to correlate with HIV-1 acquisition. Because human leukocyte antigen (HLA) class II-restricted CD4(+) T cells are involved in antibody production, we tested whether HLA class II genotypes affected HIV-1-specific antibody levels and HIV-1 acquisition in 760 individuals. Indeed, antibody responses correlated with acquisition only in the presence of single host HLA alleles. Envelope (Env)-specific immunoglobulin A (IgA) antibodies were associated with increased risk of acquisition specifically in individuals with DQB1*06. IgG antibody responses to Env amino acid positions 120 to 204 were higher and were associated with decreased risk of acquisition and increased vaccine efficacy only in the presence of DPB1*13. Screening IgG responses to overlapping peptides spanning Env 120-204 and viral sequence analysis of infected individuals defined differences in vaccine response that were associated with the presence of DPB1*13 and could be responsible for the protection observed. Overall, the underlying genetic findings indicate that HLA class II modulated the quantity, quality, and efficacy of antibody responses in the RV144 trial.
C1 [Prentice, Heather A.; Ehrenberg, Philip K.; Rolland, Morgane; Kijak, Gustavo H.; Krebs, Shelly J.; Robb, Merlin L.; Michael, Nelson L.; Kim, Jerome H.; Thomas, Rasmi] US Mil HIV Res Program, Walter Reed Army Inst Res, Silver Spring, MD 20910 USA.
[Prentice, Heather A.; Rolland, Morgane; Kijak, Gustavo H.; Krebs, Shelly J.; Robb, Merlin L.; Thomas, Rasmi] Henry M Jackson Fdn Adv Mil Med, Bethesda, MD 20818 USA.
[Tomaras, Georgia D.; Shen, Xiaoying; Yates, Nicole L.; Ferrari, Guido; Montefiori, David C.] Duke Univ, Sch Med, Duke Human Vaccine Inst, Durham, NC 27710 USA.
[Geraghty, Daniel E.; Nelson, Wyatt] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA.
[Apps, Richard] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Fong, Youyi; DeCamp, Allan; McElrath, M. Juliana; Gilbert, Peter B.] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98109 USA.
[Zolla-Pazner, Susan] NYU, Sch Med, Vet Affairs New York Harbor Healthcare Syst, New York, NY 10016 USA.
[Zolla-Pazner, Susan] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA.
[Nitayaphan, Sorachai; O'Connell, Robert J.] Armed Forces Res Inst Med Sci, US Army Med Component, Dept Retrovirol, Bangkok 10400, Thailand.
[Rerks-Ngarm, Supachai] Minist Publ Hlth, Dept Dis Control, Nonthaburi 11000, Thailand.
[Kaewkungwal, Jaranit] Mahidol Univ, Fac Trop Med, Ctr Excellence Biomed & Publ Hlth Informat BIOPHI, Bangkok 10400, Thailand.
[Pitisuttithum, Punnee] Mahidol Univ, Fac Trop Med, Vaccine Trial Ctr, Bangkok 10400, Thailand.
[Bailer, Robert T.; Koup, Richard A.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Thomas, R (reprint author), US Mil HIV Res Program, Walter Reed Army Inst Res, Silver Spring, MD 20910 USA.
EM rthomas@hivresearch.org
RI Tomaras, Georgia/J-5041-2016
FU Henry M. Jackson Foundation for the Advancement of Military Medicine
Inc. [W81XWH-07-2-0067]; U.S. Department of Defense, Bill & Melinda
Gates Foundation (Collaboration for AIDS Vaccine Discovery)
[W81XWH-07-2-0067, OPP1032144]; NIH/NIAID [UM1 AI068618, AI064518]; U.S.
National Institute of Allergy and Infectious Disease
FX This work was supported 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, Bill & Melinda Gates
Foundation (Collaboration for AIDS Vaccine Discovery, grant OPP1032144),
and the NIH/NIAID (UM1 AI068618 and Duke Center for AIDS Research
AI064518). This research was funded, in part, by the U.S. National
Institute of Allergy and Infectious Disease.
NR 43
TC 7
Z9 7
U1 0
U2 7
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 JUL 15
PY 2015
VL 7
IS 296
AR 296ra112
DI 10.1126/scitranslmed.aab4005
PG 8
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA CN9AQ
UT WOS:000358738400005
PM 26180102
ER
PT J
AU Barochia, AV
Levine, SJ
AF Barochia, Amisha V.
Levine, Stewart J.
TI A Potential Link between Serum Low-Density Lipoproteins and Asthma Reply
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Letter
C1 [Barochia, Amisha V.; Levine, Stewart J.] NIH, Bethesda, MD 20892 USA.
RP Barochia, AV (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 2
TC 0
Z9 0
U1 0
U2 0
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 JUL 15
PY 2015
VL 192
IS 2
BP 262
EP 263
PG 3
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA CN2CW
UT WOS:000358229100027
PM 26177178
ER
PT J
AU Grantz, KL
Hinkle, SN
Mendola, P
Sjaarda, LA
Leishear, K
Albert, PS
AF Grantz, Katherine L.
Hinkle, Stefanie N.
Mendola, Pauline
Sjaarda, Lindsey A.
Leishear, Kira
Albert, Paul S.
TI Differences in Risk Factors for Recurrent Versus Incident Preterm
Delivery
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE birth intervals; premature birth; reproductive history
ID PREGNANCY OUTCOMES; GESTATIONAL-AGE; BIRTH; WOMEN; COHORT; SMOKING
AB Risk factors for preterm delivery have been described, but whether risk factors differ in the context of prior preterm delivery history is less understood. We assessed whether known risk factors were different in women with versus without prior preterm delivery using medical records of the first and second singleton deliveries in 25,820 Utah women (2002-2010). Longitudinal transition models with modified Poisson regression calculated adjusted relative risks and 95% confidence intervals, with multiplicative interactions between each preterm risk factor and prior preterm delivery status to explore whether risk factors varied between incident and recurrent preterm delivery at <37 weeks. Fewer second pregnancy factors were associated with recurrent preterm delivery, including alcohol, thyroid disease, and depression. Smoking was associated with increased risk for incident (relative risk (RR) = 1.95, 95% confidence interval (CI): 1.53, 2.49) but not recurrent (RR = 1.09, 95% CI: 0.71, 1.19) preterm delivery, whereas alcohol was associated with an increased risk for recurrent (RR = 2.38, 95% CI: 1.53, 3.71) but not incident (RR = 0.98, 95% CI: 0.67, 1.43; P-interaction = 0.02 and <0.01) preterm delivery, respectively. Prior term delivery did not necessarily confer protection from known second pregnancy preterm delivery risk factors. In the setting of a prior preterm delivery, many risk factors did not persist. Prior preterm delivery history is important when assessing subsequent preterm delivery risk factors.
C1 [Grantz, Katherine L.; Hinkle, Stefanie N.; Mendola, Pauline; Sjaarda, Lindsey A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, Rockville, MD 20852 USA.
[Albert, Paul S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Intramural Populat Hlth Res, Rockville, MD 20852 USA.
[Leishear, Kira] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Glotech Inc, Div Intramural Populat Hlth Res, Rockville, MD 20852 USA.
RP Grantz, KL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, 6100 Execut Blvd,Room 7B03, Rockville, MD 20852 USA.
EM katherine.grantz@nih.gov
RI Hinkle, Stefanie/F-8253-2013;
OI Hinkle, Stefanie/0000-0003-4312-708X; Sjaarda,
Lindsey/0000-0003-0539-8110; Mendola, Pauline/0000-0001-5330-2844;
Grantz, Katherine/0000-0003-0276-8534
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [HHSN275200800002I, HHSN27500004]
FX This work was supported by the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human Development
(contracts HHSN275200800002I and HHSN27500004).
NR 25
TC 3
Z9 3
U1 1
U2 5
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 JUL 15
PY 2015
VL 182
IS 2
BP 157
EP 167
DI 10.1093/aje/kwv032
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CM9UJ
UT WOS:000358054200009
PM 26033931
ER
PT J
AU Hasenour, CM
Wall, ML
Ridley, DE
Hughey, CC
James, FD
Wasserman, DH
Young, JD
AF Hasenour, Clinton M.
Wall, Martha L.
Ridley, D. Emerson
Hughey, Curtis C.
James, Freyja D.
Wasserman, David H.
Young, Jamey D.
TI Mass spectrometry-based microassay of H-2 and C-13 plasma glucose
labeling to quantify liver metabolic fluxes in vivo
SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
LA English
DT Article
DE metabolic flux analysis; liver physiology; isotopomer model; nutrient
metabolism; gluconeogenesis
ID CITRIC-ACID CYCLE; PERFUSED RAT-LIVER; ACTIVATED PROTEIN-KINASE; HEPATIC
PYRUVATE-KINASE; KREBS CYCLE; TCA CYCLE; ENERGY-STATE; FATTY LIVER;
GLUCONEOGENESIS; GLUCAGON
AB Mouse models designed to examine hepatic metabolism are critical to diabetes and obesity research. Thus, a microscale method to quantitatively assess hepatic glucose and intermediary metabolism in conscious, unrestrained mice was developed. [C-13(3)] propionate, [H-2(2)] water, and [6,6-H-2(2)] glucose isotopes were delivered intravenously in short- (9 h) and long-term-fasted (19 h) C57BL/6J mice. GC-MS and mass isotopomer distribution (MID) analysis were performed on three 40-mu l arterial plasma glucose samples obtained during the euglycemic isotopic steady state. Model-based regression of hepatic glucose and citric acid cycle (CAC)-related fluxes was performed using a comprehensive isotopomer model to track carbon and hydrogen atom transitions through the network and thereby simulate the MIDs of measured fragment ions. Glucose-6-phosphate production from glycogen diminished, and endogenous glucose production was exclusively gluconeogenic with prolonged fasting. Gluconeogenic flux from phosphoenolpyruvate (PEP) remained stable, whereas that from glycerol modestly increased from short- to long-term fasting. CAC flux [i.e., citrate synthase (V-CS)] was reduced with long-term fasting. Interestingly, anaplerosis and cataplerosis increased with fast duration; accordingly, pyruvate carboxylation and the conversion of oxaloacetate to PEP were severalfold higher than V-CS in long-term fasted mice. This method utilizes state-of-the-art in vivo methodology and comprehensive isotopomer modeling to quantify hepatic glucose and intermediary fluxes during physiological stress in mice. The small plasma requirements permit serial sampling without stress and the affirmation of steady-state glucose kinetics. Furthermore, the approach can accommodate a broad range of modeling assumptions, isotope tracers, and measurement inputs without the need to introduce ad hoc mathematical approximations.
C1 [Hasenour, Clinton M.; Ridley, D. Emerson; Hughey, Curtis C.; Wasserman, David H.; Young, Jamey D.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37235 USA.
[Wall, Martha L.; Young, Jamey D.] Vanderbilt Univ, Dept Chem & Biomol Engn, Nashville, TN 37235 USA.
[James, Freyja D.; Wasserman, David H.] Vanderbilt Univ, Mouse Metab Phenotyping Ctr, Nashville, TN 37235 USA.
RP Young, JD (reprint author), Vanderbilt Univ, Dept Chem & Biomol Engn, PMB 351604,2301 Vanderbilt Pl, Nashville, TN 37235 USA.
EM j.d.young@vanderbilt.edu
RI Young, Jamey/A-5857-2012
FU National Institute of Diabetes and Digestive and Kidney Diseases Grant
[U24-DK-59637, R37-DK-50277, U24-DK-076169]; Vanderbilt Molecular
Endocrinology Training Program [5-T32-DK07563]; Canadian Diabetes
Association Postdoctoral Fellowship [PF-3-14-4687-CH]
FX This research was supported by National Institute of Diabetes and
Digestive and Kidney Diseases Grants U24-DK-59637, R37-DK-50277 (D. H.
Wasserman), and U24-DK-076169 (J. D. Young). C. M. Hasenour and M. L.
Wall were also supported by the Vanderbilt Molecular Endocrinology
Training Program (5-T32-DK07563). C. C. Hughey was supported by the
Canadian Diabetes Association Postdoctoral Fellowship (PF-3-14-4687-CH).
NR 65
TC 9
Z9 9
U1 3
U2 17
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0193-1849
EI 1522-1555
J9 AM J PHYSIOL-ENDOC M
JI Am. J. Physiol.-Endocrinol. Metab.
PD JUL 15
PY 2015
VL 309
IS 2
BP E191
EP E203
DI 10.1152/ajpendo.00003.2015
PG 13
WC Endocrinology & Metabolism; Physiology
SC Endocrinology & Metabolism; Physiology
GA CM8YH
UT WOS:000357989100011
PM 25991647
ER
PT J
AU Rieder, SA
Metidji, A
Glass, DD
Thornton, AM
Ikeda, T
Morgan, BA
Shevach, EM
AF Rieder, Sadiye Amcaoglu
Metidji, Amina
Glass, Deborah Dacek
Thornton, Angela M.
Ikeda, Tohru
Morgan, Bruce A.
Shevach, Ethan M.
TI Eos Is Redundant for Regulatory T Cell Function but Plays an Important
Role in IL-2 and Th17 Production by CD4(+) Conventional T Cells
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID IKAROS FAMILY; RECEPTOR; DIFFERENTIATION; EXPRESSION; SIGNATURE;
IMMUNITY
AB Eos belongs to the Ikaros family of transcription factors. It was reported to be a regulatory T cell (Treg) signature gene, to play a critical role in Treg suppressor functions, and to maintain Treg stability. We used mice with a global deficiency in Eos to re-examine the role of Eos expression in both Tregs and conventional T cells (Tconvs). Tregs from Eos-deficient (Eos(-/-)) mice developed normally, displayed a normal Treg phenotype, and exhibited normal suppressor function in vitro. Eos(-/-) Tregs were as effective as Tregs from wild-type (WT) mice in suppressing inflammation in a model of inflammatory bowel disease. Bone marrow (BM) from Eos(-/-) mice was as effective as that from WT mice in controlling T cell activation when used to reconstitute immunodeficient mice in the presence of scurfy fetal liver cells. Surprisingly, Eos was expressed in activated Tconvs and was required for IL-2 production, CD25 expression, and proliferation in vitro by CD4(+) Tconvs. Eos(-/-) mice developed more severe experimental autoimmune encephalomyelitis than WT mice, displayed increased numbers of effector T cells in the periphery and CNS, and amplified IL-17 production. In conclusion, our studies are not consistent with a role for Eos in Treg development and function but demonstrate that Eos plays an important role in the activation and differentiation of Tconvs.
C1 [Rieder, Sadiye Amcaoglu; Metidji, Amina; Glass, Deborah Dacek; Thornton, Angela M.; Shevach, Ethan M.] NIAID, Immunol Lab, Bethesda, MD 20892 USA.
[Ikeda, Tohru; Morgan, Bruce A.] Harvard Univ, Sch Med, Dept Dermatol, Cutaneous Biol Res Ctr, Boston, MA 02129 USA.
[Ikeda, Tohru; Morgan, Bruce A.] Massachusetts Gen Hosp, Boston, MA 02129 USA.
RP Shevach, EM (reprint author), NIAID, Immunol Lab, Bldg 10,Room 11N315,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA.
EM eshevach@niaid.nih.gov
FU Intramural Program of the National Institute of Allergy and Infectious
Diseases
FX This work was supported by the Intramural Program of the National
Institute of Allergy and Infectious Diseases.
NR 19
TC 2
Z9 2
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD JUL 15
PY 2015
VL 195
IS 2
BP 553
EP 563
DI 10.4049/jimmunol.1500627
PG 11
WC Immunology
SC Immunology
GA CM9YM
UT WOS:000358066800016
PM 26062998
ER
PT J
AU Wheatley, AK
Whittle, JRR
Lingwood, D
Kanekiyo, M
Yassine, HM
Ma, SS
Narpala, SR
Prabhakaran, MS
Matus-Nicodemos, RA
Bailer, RT
Nabel, GJ
Graham, BS
Ledgerwood, JE
Koup, RA
McDermott, AB
AF Wheatley, Adam K.
Whittle, James R. R.
Lingwood, Daniel
Kanekiyo, Masaru
Yassine, Hadi M.
Ma, Steven S.
Narpala, Sandeep R.
Prabhakaran, Madhu S.
Matus-Nicodemos, Rodrigo A.
Bailer, Robert T.
Nabel, Gary J.
Graham, Barney S.
Ledgerwood, Julie E.
Koup, Richard A.
McDermott, Adrian B.
TI H5N1 Vaccine-Elicited Memory B Cells Are Genetically Constrained by the
IGHV Locus in the Recognition of a Neutralizing Epitope in the
Hemagglutinin Stem
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID MONOCLONAL-ANTIBODIES; INFLUENZA ANTIBODIES; STALK ANTIBODIES;
EXPRESSION; HUMANS; INDUCTION; DIFFERENTIATION; INTERVAL; VIRUSES
AB Because of significant viral diversity, vaccines that elicit durable and broad protection against influenza have been elusive. Recent research has focused on the potential of highly conserved regions of the viral hemagglutinin (HA) as targets for broadly neutralizing Ab responses. Abs that bind the highly conserved stem or stalk of HA can be elicited by vaccination in humans and animal models and neutralize diverse influenza strains. However, the frequency and phenotype of HA stem-specific B cells in vivo remain unclear. In this article, we characterize HA stem-specific B cell responses following H5N1 vaccination and describe the re-expansion of a pre-existing population of memory B cells specific for stem epitopes. This population uses primarily, but not exclusively, IGHV1-69- based Igs for HA recognition. However, within some subjects, allelic polymorphism at the ighv1-69 locus can limit IGHV1-69 immunodominance and may reduce circulating frequencies of stem-reactive B cells in vivo. The accurate definition of allelic selection, recombination requirements, and ontogeny of neutralizing Ab responses to influenza will aid rational influenza vaccine design.
C1 [Wheatley, Adam K.; Whittle, James R. R.; Kanekiyo, Masaru; Yassine, Hadi M.; Ma, Steven S.; Narpala, Sandeep R.; Prabhakaran, Madhu S.; Matus-Nicodemos, Rodrigo A.; Bailer, Robert T.; Graham, Barney S.; Ledgerwood, Julie E.; Koup, Richard A.; McDermott, Adrian B.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Lingwood, Daniel] MIT & Harvard, Ragon Inst MGH, Boston, MA USA.
[Nabel, Gary J.] Sanofi, Cambridge, MA 02139 USA.
RP McDermott, AB (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr,Room 3508, Bethesda, MD 20892 USA.
EM adrian.mcdermott@nih.gov
OI Wheatley, Adam/0000-0002-5593-9387
FU Intramural Research Program of the Vaccine Research Center, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health
FX This work was supported by the Intramural Research Program of the
Vaccine Research Center, National Institute of Allergy and Infectious
Diseases, National Institutes of Health.
NR 37
TC 10
Z9 10
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 JUL 15
PY 2015
VL 195
IS 2
BP 602
EP 610
DI 10.4049/jimmunol.1402835
PG 9
WC Immunology
SC Immunology
GA CM9YM
UT WOS:000358066800020
PM 26078272
ER
PT J
AU Klein, M
Bruhl, TJ
Staudt, V
Reuter, S
Grebe, N
Gerlitzki, B
Hoffmann, M
Bohn, T
Ulges, A
Stergiou, N
De Graaf, J
Lower, M
Taube, C
Becker, M
Hain, T
Dietzen, S
Stassen, M
Huber, M
Lohoff, M
Chagas, AC
Andersen, J
Kotal, J
Langhansova, H
Kopecky, J
Schild, H
Kotsyfakis, M
Schmitt, E
Bopp, T
AF Klein, Matthias
Bruehl, Till-Julius
Staudt, Valerie
Reuter, Sebastian
Grebe, Nadine
Gerlitzki, Bastian
Hoffmann, Markus
Bohn, Toszka
Ulges, Alexander
Stergiou, Natascha
De Graaf, Jos
Loewer, Martin
Taube, Christian
Becker, Marc
Hain, Tobias
Dietzen, Sarah
Stassen, Michael
Huber, Magdalena
Lohoff, Michael
Chagas, Andrezza Campos
Andersen, John
Kotal, Jan
Langhansova, Helena
Kopecky, Jan
Schild, Hansjoerg
Kotsyfakis, Michalis
Schmitt, Edgar
Bopp, Tobias
TI Tick Salivary Sialostatin L Represses the Initiation of Immune Responses
by Targeting IRF4-Dependent Transcription in Murine Mast Cells
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID T-CELLS; TRANSGENIC MICE; IL-9 PRODUCTION; ASTHMA MODEL; INFLAMMATION;
EXPRESSION; INTERLEUKIN-9; CYTOKINES; PROTEINS; ACTIVATION
AB Coevolution of ticks and the vertebrate immune system has led to the development of immunosuppressive molecules that prevent immediate response of skin-resident immune cells to quickly fend off the parasite. In this article, we demonstrate that the tick-derived immunosuppressor sialostatin L restrains IL-9 production by mast cells, whereas degranulation and IL-6 expression are both unaffected. In addition, the expression of IL-1 beta and IRF4 is strongly reduced in the presence of sialostatin L. Correspondingly, IRF4-or IL-1R-deficient mast cells exhibit a strong impairment in IL-9 production, demonstrating the importance of IRF4 and IL-1 in the regulation of the Il9 locus in mast cells. Furthermore, IRF4 binds to the promoters of Il1b and Il9, suggesting that sialostatin L suppresses mast cell-derived IL-9 preferentially by inhibiting IRF4. In an experimental asthma model, mast cell-specific deficiency in IRF4 or administration of sialostatin L results in a strong reduction in asthma symptoms, demonstrating the immunosuppressive potency of tick-derived molecules.
C1 [Klein, Matthias; Bruehl, Till-Julius; Staudt, Valerie; Grebe, Nadine; Gerlitzki, Bastian; Hoffmann, Markus; Bohn, Toszka; Ulges, Alexander; Stergiou, Natascha; Becker, Marc; Hain, Tobias; Dietzen, Sarah; Stassen, Michael; Schild, Hansjoerg; Schmitt, Edgar; Bopp, Tobias] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Inst Immunol, D-55131 Mainz, Germany.
[Reuter, Sebastian] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Med Clin 3, D-55131 Mainz, Germany.
[De Graaf, Jos; Loewer, Martin] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Translat Oncol, D-55131 Mainz, Germany.
[Taube, Christian] Leiden Univ, Med Ctr, Dept Pulmonol, NL-2333 ZA Leiden, Netherlands.
[Huber, Magdalena; Lohoff, Michael] Inst Med Mikrobiol & Krankenhaushyg, D-35043 Marburg, Germany.
[Chagas, Andrezza Campos; Andersen, John] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
[Kotal, Jan; Langhansova, Helena; Kopecky, Jan; Kotsyfakis, Michalis] Acad Sci Czech Republic, Inst Parasitol, Ctr Biol, Ceske Budejovice 37005, Czech Republic.
[Langhansova, Helena; Kopecky, Jan] Univ South Bohemia, Fac Sci, Ceske Budejovice 37005, Czech Republic.
RP Bopp, T (reprint author), Johannes Gutenberg Univ Mainz, Univ Med Ctr, Inst Immunol, Bldg 708,Langenbeckstr 1, D-55131 Mainz, Germany.
EM boppt@uni-mainz.de
RI Kotsyfakis, Michail/G-9525-2014; Langhansova, Helena /G-9292-2014;
Kopecky, Jan/G-9347-2014;
OI Kotsyfakis, Michail/0000-0002-7526-1876; Taube,
Christian/0000-0002-3546-1398; Baumgart, Nadine/0000-0002-6684-0198
FU Deutsche Forschungsgemeinschaft [DFG BO 3306/1-1, SCHM 1014/7-1, SCHM
1014/5-1, SFB 1066, SFB TR22, GRK 1043]; Behring-Rontgen-Stiftung;
Forschungszentrum Immunologie of the University Medical Center; Czech
Science Foundation Grant [P302/11/J029]; Grant Agency of the Czech
Republic [P502/12/2409]; Intramural Research Program of the Division of
Intramural Research, National Institute of Allergy and Infectious
Diseases, National Institutes of Health
FX This work was supported by Deutsche Forschungsgemeinschaft Grants DFG BO
3306/1-1, SCHM 1014/7-1, SCHM 1014/5-1, SFB 1066 Project B1 (to E.S.)
and Project B8 (to T.B.), SFB TR22 A16 (to M. Lohoff), and GRK 1043:
International Graduate School of Immunotherapy Project C4 (to E.S. and
T.B.); the Behring-Rontgen-Stiftung (to M. Lohoff); the
Forschungszentrum Immunologie of the University Medical Center (to E.S.
and T.B.); and Czech Science Foundation Grant P302/11/J029 (to H.L., J.
Kopecky, and M. Kotsyfakis). M. Kotsyfakis and J. Kopecky received
financial support from Grant Agency of the Czech Republic Grant
P502/12/2409. A.C.C. and J.A. were supported by the Intramural Research
Program of the Division of Intramural Research, 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 39
TC 4
Z9 5
U1 3
U2 10
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 JUL 15
PY 2015
VL 195
IS 2
BP 621
EP 631
DI 10.4049/jimmunol.1401823
PG 11
WC Immunology
SC Immunology
GA CM9YM
UT WOS:000358066800022
PM 26078269
ER
PT J
AU Dastgheyb, S
Hickok, NJ
Otto, M
AF Dastgheyb, Sana
Hickok, Noreen J.
Otto, Michael
TI Biofilm-Like Aggregation of Staphylococcus epidermidis in Synovial Fluid
Reply
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Letter
ID MATURATION; INFECTIONS
C1 [Dastgheyb, Sana; Otto, Michael] NIAID, NIH, Bethesda, MD 20892 USA.
[Dastgheyb, Sana; Hickok, Noreen J.] Thomas Jefferson Univ, Dept Orthoped Surg, Philadelphia, PA 19107 USA.
RP Otto, M (reprint author), NIAID, Lab Human Bacterial Pathogenesis, NIH, Bldg 33 1W10,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM motto@niaid.nih.gov
OI Dastgheyb, Sana/0000-0001-8275-1614
FU Intramural NIH HHS; NIAID NIH HHS [ZIA AI000904, ZIA AI000904-13]; NICHD
NIH HHS [HD06153]; NIDCR NIH HHS [DE019901, R01 DE019901]
NR 7
TC 0
Z9 0
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 JUL 15
PY 2015
VL 212
IS 2
BP 336
EP 337
DI 10.1093/infdis/jiv097
PG 3
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA CM6TQ
UT WOS:000357823300021
PM 25712972
ER
PT J
AU Abdala, AP
Paton, JFR
Smith, JC
AF Abdala, Ana Paula
Paton, Julian F. R.
Smith, Jeffrey C.
TI Defining inhibitory neurone function in respiratory circuits:
opportunities with optogenetics?
SO JOURNAL OF PHYSIOLOGY-LONDON
LA English
DT Review
ID PRE-BOTZINGER COMPLEX; BRAIN-STEM; GLYCINERGIC INHIBITION; VENTROLATERAL
MEDULLA; PREBOTZINGER COMPLEX; PATTERN GENERATION; GABAERGIC NEURONS;
RHYTHM GENERATION; GABA(A) RECEPTORS; IN-VIVO
AB Pharmacological and mathematical modelling studies support the view that synaptic inhibition in mammalian brainstem respiratory circuits is essential for generating normal and stable breathing movements. GABAergic and glycinergic neurones are known components of these circuits but their precise functional roles have not been established, especially within key microcircuits of the respiratory pre-Botzinger (pre-BotC) and Botzinger (BotC) complexes involved in phasic control of respiratory pump and airway muscles. Here, we review briefly current concepts of relevant complexities of inhibitory synapses and the importance of synaptic inhibition in the operation of these microcircuits. We highlight results and limitations of classical pharmacological studies that have suggested critical functions of synaptic inhibition. We then explore the potential opportunities for optogenetic strategies that represent a promising new approach for interrogating function of inhibitory circuits, including a hypothetical wish list for optogenetic approaches to allow expedient application of this technology. We conclude that recent technical advances in optogenetics should provide a means to understand the role of functionally select and regionally confined subsets of inhibitory neurones in key respiratory circuits such as those in the pre-BotC and BotC.
C1 [Abdala, Ana Paula; Paton, Julian F. R.] Univ Bristol, Sch Physiol & Pharmacol, Bristol CardioVasc, Bristol BS8 1TD, Avon, England.
[Smith, Jeffrey C.] NINDS, NIH, Cellular & Syst Neurobiol Sect, Bethesda, MD 20892 USA.
RP Abdala, AP (reprint author), Univ Bristol, Sch Physiol & Pharmacol, Med Sci Bldg, Bristol BS8 1TD, Avon, England.
EM ana.abdala@bristol.ac.uk
RI Abdala, Ana Paula/G-9104-2014;
OI Abdala, Ana Paula/0000-0001-6051-2591; Paton, Julian/0000-0001-7410-2913
FU National Institutes of Health [NIH - R01 NS069220]; International Rett
Syndrome Foundation (IRSF); Intramural Research Program of the NIH,
NINDS
FX A.P.A. and J.F.R.P. are funded by the National Institutes of Health (NIH
- R01 NS069220). A.P.A. is funded by the International Rett Syndrome
Foundation (IRSF). J.C.S. is supported by the Intramural Research
Program of the NIH, NINDS.
NR 102
TC 4
Z9 4
U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3751
EI 1469-7793
J9 J PHYSIOL-LONDON
JI J. Physiol.-London
PD JUL 15
PY 2015
VL 593
IS 14
BP 3033
EP 3045
DI 10.1113/jphysiol.2014.280610
PG 13
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA CM9QG
UT WOS:000358043200011
PM 25384785
ER
PT J
AU Wu, ZJ
Hiriyanna, S
Qian, HH
Mookherjee, S
Campos, MM
Gao, C
Fariss, R
Sieving, PA
Li, TS
Colosi, P
Swaroop, A
AF Wu, Zhijian
Hiriyanna, Suja
Qian, Haohua
Mookherjee, Suddhasil
Campos, Maria M.
Gao, Chun
Fariss, Robert
Sieving, Paul A.
Li, Tiansen
Colosi, Peter
Swaroop, Anand
TI A long-term efficacy study of gene replacement therapy for
RPGR-associated retinal degeneration
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID LINKED RETINITIS-PIGMENTOSA; LEBERS CONGENITAL AMAUROSIS;
ADENOASSOCIATED VIRUS; CLINICAL-TRIAL; HUMAN TISSUES; IN-VIVO;
MUTATIONS; MOUSE; ROD; DISEASE
AB Mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene account for > 70% of X-linked retinitis pigmentosa (XLRP) and 15-20% of all inherited retinal degeneration. Gene replacement therapy for RPGR-XLRP was hampered by the relatively slow disease progression in mouse models and by difficulties in cloning the full-length RPGR-ORF15 cDNA that includes a purine-rich 3'-coding region; however, its effectiveness has recently been demonstrated in four dogs with RPGR mutations. To advance the therapy to clinical stage, we generated new stable vectors in AAV8 or AAV9 carrying mouse and human full-length RPGR-ORF15-coding sequence and conducted a comprehensive long-term dose-efficacy study in Rpgr-knockout mice. After validating their ability to produce full-length proteins that localize to photoreceptor connecting cilia, we evaluated various vector doses in mice during a 2-year study. We demonstrate that eyes treated with a single injection of mouse or human RPGR-ORF15 vector at an optimal dose maintained the expression of RPGR-ORF15 throughout the study duration and exhibited higher electroretinogram amplitude, thicker photoreceptor layer and better targeting of opsins to outer segments compared with sham-treated eyes. Furthermore, mice that received treatment at an advanced age also showed remarkable preservation of retinal structure and function. Retinal toxicity was observed at high vector doses, highlighting the importance of careful dose optimization in future clinical experiments. Our long-term dose-efficacy study should facilitate the design of human trials with human RPGR-ORF15 vector as a clinical candidate.
C1 [Wu, Zhijian; Hiriyanna, Suja; Qian, Haohua; Mookherjee, Suddhasil; Campos, Maria M.; Gao, Chun; Fariss, Robert; Sieving, Paul A.; Li, Tiansen; Colosi, Peter; Swaroop, Anand] NEI, NIH, Bethesda, MD 20892 USA.
RP Wu, ZJ (reprint author), NEI, Ocular Gene Therapy Core, NIH, 6 Ctr Dr,Room 306,MSC 0610, Bethesda, MD 20892 USA.
EM wuzh@mail.nih.gov; swaroopa@nei.nih.gov
OI Swaroop, Anand/0000-0002-1975-1141
FU Intramural NIH HHS
NR 50
TC 13
Z9 13
U1 0
U2 5
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 JUL 15
PY 2015
VL 24
IS 14
BP 3956
EP 3970
DI 10.1093/hmg/ddv134
PG 15
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA CM2PV
UT WOS:000357524700007
PM 25877300
ER
PT J
AU Keck, TM
Banala, AK
Slack, RD
Burzynski, C
Bonifazi, A
Okunola-Bakare, OM
Moore, M
Deschamps, JR
Rais, R
Slusher, BS
Newman, AH
AF Keck, Thomas M.
Banala, Ashwini K.
Slack, Rachel D.
Burzynski, Caitlin
Bonifazi, Alessandro
Okunola-Bakare, Oluyomi M.
Moore, Martin
Deschamps, Jeffrey R.
Rais, Rana
Slusher, Barbara S.
Newman, Amy Hauck
TI Using click chemistry toward novel 1,2,3-triazole-linked dopamine D3
receptor ligands
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE Dopamine D3 receptor; Click chemistry; 1,2,3-Triazole; Bioisoteric
replacement; Metabolic stability; Structure-activity relationships
ID FUNCTIONALIZED LINKING CHAINS; ABUSE THERAPEUTIC AGENTS; TERMINAL
ALKYNES; CURRENT PERSPECTIVES; MEDICINAL CHEMISTRY; D-3 RECEPTORS;
ANTAGONISTS; INHIBITORS; CYCLOADDITION; DESIGN
AB The dopamine D3 receptor (D3R) is a target of pharmacotherapeutic interest in a variety of neurological disorders including schizophrenia, Parkinson's disease, restless leg syndrome, and drug addiction. A common molecular template used in the development of D3R-selective antagonists and partial agonists incorporates a butylamide linker between two pharmacophores, a phenylpiperazine moiety and an extended aryl ring system. The series of compounds described herein incorporates a change to that chemical template, replacing the amide functional group in the linker chain with a 1,2,3-triazole group. Although the amide linker in the 4-phenylpiperazine class of D3R ligands has been previously deemed critical for high D3R affinity and selectivity, the 1,2,3-triazole moiety serves as a suitable bioisosteric replacement and maintains desired D3R-binding functionality of the compounds. Additionally, using mouse liver microsomes to evaluate CYP450-mediated phase I metabolism, we determined that novel 1,2,3-triazole-containing compounds modestly improves metabolic stability compared to amide-containing analogues. The 1,2,3-triazole moiety allows for the modular attachment of chemical subunit libraries using copper-catalyzed azide-alkyne cycloaddition click chemistry, increasing the range of chemical entities that can be designed, synthesized, and developed toward D3R-selective therapeutic agents. Published by Elsevier Ltd.
C1 [Keck, Thomas M.; Banala, Ashwini K.; Slack, Rachel D.; Burzynski, Caitlin; Bonifazi, Alessandro; Okunola-Bakare, Oluyomi M.; Newman, Amy Hauck] NIDA, Med Chem Sect, Mol Targets & Medicat Discovery Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
[Moore, Martin; Deschamps, Jeffrey R.] Naval Res Lab, Washington, DC 20375 USA.
[Rais, Rana; Slusher, Barbara S.] Johns Hopkins Univ, Brain Sci Inst, Baltimore, MD 21205 USA.
[Slusher, Barbara S.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21205 USA.
RP Newman, AH (reprint author), NIDA, Med Chem Sect, Mol Targets & Medicat Discovery Branch, Intramural Res Program,NIH, 333 Cassell Dr, Baltimore, MD 21224 USA.
EM anewman@intra.nida.nih.gov
RI Keck, Thomas/G-9798-2012
OI Keck, Thomas/0000-0003-1845-9373
FU NIDA Intramural Research Program; NIH Postdoctoral Intramural Research
Training Award (IRTA) Fellowships; NIH Post-baccalaureate IRTA
Fellowship; NIDA [Y1-DA1101]
FX This research was funded by the NIDA Intramural Research Program.
T.M.K., A.K.B., R.D.S., A.B. and O.M.O.-B. were supported by NIH
Postdoctoral Intramural Research Training Award (IRTA) Fellowships. C.B.
was supported by an NIH Post-baccalaureate IRTA Fellowship.
Crystallographic studies were supported by NIDA contract Y1-DA1101. HEK
293 cells were generously provided by Dr. David Sibley of NINDS. Thanks
to Ben Free and Theresa Kopajtic for help in developing the radioligand
binding assay. Thanks to Catherine Schweppe and Michael Ellenberger for
technical assistance with the radioligand binding studies. Thanks to
Elie Pommier for technical assistance with the metabolic studies.
NR 56
TC 5
Z9 5
U1 5
U2 32
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0968-0896
EI 1464-3391
J9 BIOORGAN MED CHEM
JI Bioorg. Med. Chem.
PD JUL 15
PY 2015
VL 23
IS 14
BP 4000
EP 4012
DI 10.1016/j.bmc.2015.01.017
PG 13
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA CK0VV
UT WOS:000355924200012
PM 25650314
ER
PT J
AU Trujillo, K
Paoletta, S
Kiselev, E
Jacobson, KA
AF Trujillo, Kevin
Paoletta, Silvia
Kiselev, Evgeny
Jacobson, Kenneth A.
TI Molecular modeling of the human P2Y(14) receptor: A template for
structure-based design of selective agonist ligands
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE G protein-coupled receptor; Homology modeling; Docking; Uracil
nucleotides; P2Y(14) receptor
ID GENERAL FORCE-FIELD; PROTEIN-COUPLED RECEPTORS; ANGSTROM
CRYSTAL-STRUCTURE; CONFORMATIONAL PREFERENCE; DYNAMICS SIMULATIONS;
3-DIMENSIONAL MODELS; P2Y RECEPTORS; BINDING-SITE; ANTAGONISTS;
IDENTIFICATION
AB The P2Y(14) receptor (P2Y(14)R) is a Gi protein-coupled receptor that is activated by uracil nucleotides UDP and UDP-glucose. The P2Y(14)R structure has yet to be solved through X-ray crystallography, but the recent agonist-bound crystal structure of the P2Y(12)R provides a potentially suitable template for its homology modeling for rational structure-based design of selective and high-affinity ligands. In this study, we applied ligand docking and molecular dynamics refinement to a P2Y(14)R homology model to qualitatively explain structure-activity relationships of previously published synthetic nucleotide analogues and to probe the quality of P2Y14R homology modeling as a template for structure-based design. The P2Y(14)R model supports the hypothesis of a conserved binding mode of nucleotides in the three P2Y(12)-like receptors involving functionally conserved residues. We predict phosphate group interactions with R253(6.55), K277(7.35), Y256(6.5)8 and Q260(6.62), nucleobase (anti-conformation) pi-pi stacking with Y102(3.33) and the role of F191(5.42) as a means for selectivity among P2Y(12)-like receptors. The glucose moiety of UDP-glucose docked in a secondary subpocket at the P2Y(14)R homology model. Thus, P2Y(14)R homology modeling may allow detailed prediction of interactions to facilitate the design of high affinity, selective agonists as pharmacological tools to study the P2Y(14)R. Published by Elsevier Ltd.
C1 [Trujillo, Kevin; Paoletta, Silvia; Kiselev, Evgeny; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA.
EM kajacobs@helix.nih.gov
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
FU NIH Undergraduate Scholarship Program (UGSP); NIGMS Postdoctoral
Research Associate (PRAT) program; NIDDK [Z01 DK031126]
FX Funding from the NIH Undergraduate Scholarship Program (UGSP) to KT, the
NIGMS Postdoctoral Research Associate (PRAT) program to EK and the
Intramural Research Program of NIDDK (Z01 DK031126) is gratefully
acknowledged.
NR 46
TC 7
Z9 7
U1 3
U2 13
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0968-0896
EI 1464-3391
J9 BIOORGAN MED CHEM
JI Bioorg. Med. Chem.
PD JUL 15
PY 2015
VL 23
IS 14
BP 4056
EP 4064
DI 10.1016/j.bmc.2015.03.042
PG 9
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA CK0VV
UT WOS:000355924200017
PM 25868749
ER
PT J
AU Haight, TJ
Bryan, RN
Erus, G
Davatzikos, C
Jacobs, DR
D'Esposito, M
Lewis, CE
Launer, LJ
AF Haight, Thaddeus J.
Bryan, R. Nick
Erus, Guray
Davatzikos, Christos
Jacobs, David R.
D'Esposito, Mark
Lewis, Cora E.
Launer, Lenore J.
TI Vascular risk factors, cerebrovascular reactivity, and the default-mode
brain network
SO NEUROIMAGE
LA English
DT Article
DE Alzheimer's disease; Neurophysiology; Vascular risk factors
ID MILD COGNITIVE IMPAIRMENT; CEREBRAL-BLOOD-FLOW; STATE FUNCTIONAL
CONNECTIVITY; ALZHEIMERS-DISEASE; LATE-LIFE; OLDER-ADULTS; HIPPOCAMPAL
ACTIVATION; ELDERLY POPULATION; HYPOTHETICAL MODEL; DYNAMIC BIOMARKERS
AB Cumulating evidence from epidemiologic studies implicates cardiovascular health and cerebrovascular function in several brain diseases in late life. We examined vascular risk factors with respect to a cerebrovascular measure of brain functioning in subjects in mid-life, which could represent a marker of brain changes in later life. Breathhold functional MRI (fMRI) was performed in 541 women and men (mean age 50.4 years) from the Coronary Artery Risk Development in Young Adults (CARDIA) Brain MRI sub-study. Cerebrovascular reactivity (CVR) was quantified as percentage change in blood-oxygen level dependent (BOLD) signal in activated voxels, which was mapped to a common brain template and log-transformed. Mean CVR was calculated for anatomic regions underlying the default-mode network (DMN) - a network implicated in AD and other brain disorders -in addition to areas considered to be relatively spared in the disease (e.g. occipital lobe), which were utilized as reference regions. Mean CVR was significantly reduced in the posterior cingulate/precuneus (beta = -0.063, 95% CI: -0.106, -0.020), anterior cingulate (beta = -0.055, 95% CI: -0.101, -0.010), and medial frontal lobe (beta = -0.050, 95% CI: -0.092, -0.008) relative to mean CVR in the occipital lobe, after adjustment for age, sex, race, education, and smoking status, in subjects with pre-hypertension/hypertension compared to normotensive subjects. By contrast, mean CVR was lower, but not significantly, in the inferior parietal lobe (beta = -0.024, 95% CI: -0.062, 0.014) and the hippocampus (beta = -0.006, 95% CI: -0.062, 0.050) relative to mean CVR in the occipital lobe. Similar results were observed in subjects with diabetes and dyslipidemia compared to those without these conditions, though the differences were non-significant. Reduced CVR may represent diminished vascular functionality for the DMN for individuals with prehypertension/hypertension in midlife, and may serve as a preclinical marker for brain dysfunction in later life. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Haight, Thaddeus J.; Launer, Lenore J.] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20814 USA.
[Bryan, R. Nick; Erus, Guray; Davatzikos, Christos] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA.
[Jacobs, David R.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[D'Esposito, Mark] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA.
[Lewis, Cora E.] Univ Alabama Birmingham, Dept Med, Div Prevent Med, Birmingham, AL 35294 USA.
RP Haight, TJ (reprint author), NIA, Lab Epidemiol & Populat Sci, 7201 Wisconsin Ave,Room 3C309, Bethesda, MD 20814 USA.
EM tad.haight@nih.gov
FU National Heart, Lung, and Blood Institute (NHLBI) [HHSN268201300025C,
HHSN2682013 00026C, HHSN268201300027C, HHSN268201300028C, HHSN26820
1300029C, HHSN268200900041C, AG0005]; Intramural Research Program of the
National Institute on Aging (NIA); NIA
FX The Coronary Artery Risk Development in Young Adults Study (CARDIA) is
supported by contracts HHSN268201300025C, HHSN2682013 00026C,
HHSN268201300027C, HHSN268201300028C, HHSN26820 1300029C, and
HHSN268200900041C from the National Heart, Lung, and Blood Institute
(NHLBI), the Intramural Research Program of the National Institute on
Aging (NIA), and an intra-agency agreement between NIA and NHLBI
(AG0005).
NR 74
TC 4
Z9 4
U1 0
U2 14
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 JUL 15
PY 2015
VL 115
BP 7
EP 16
DI 10.1016/j.neuroimage.2015.04.039
PG 10
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA CK0XU
UT WOS:000355929800002
PM 25917517
ER
PT J
AU Machiela, MJ
Hsiung, CA
Shu, XO
Seow, WJ
Wang, ZM
Matsuo, K
Hong, YC
Seow, A
Wu, C
Hosgood, HD
Chen, KX
Wang, JC
Wen, WQ
Cawthon, R
Chatterjee, N
Hu, W
Caporaso, NE
Park, JY
Chen, CJ
Kim, YH
Kim, YT
Landi, MT
Shen, HB
Lawrence, C
Burdett, L
Yeager, M
Chang, IS
Mitsudomi, T
Kim, HN
Chang, GC
Bassig, BA
Tucker, M
Wei, FS
Yin, ZH
An, SJ
Qian, BY
Lee, VHF
Lu, DR
Liu, JJ
Jeon, HS
Hsiao, CF
Sung, JS
Kim, JH
Gao, YT
Tsai, YH
Jung, YJ
Guo, H
Hu, ZB
Hutchinson, A
Wang, WC
Klein, RJ
Chung, CC
Oh, IJ
Chen, KY
Berndt, SI
Wu, W
Chang, J
Zhang, XC
Huang, MS
Zheng, H
Wang, JW
Zhao, XY
Li, YQ
Choi, JE
Su, WC
Park, KH
Sung, SW
Chen, YM
Liu, L
Kang, CH
Hu, LM
Chen, CH
Pao, W
Kim, YC
Yang, TY
Xu, J
Guan, P
Tan, W
Su, J
Wang, CL
Li, HX
Sihoe, ADL
Zhao, ZH
Chen, Y
Choi, YY
Hung, JY
Kim, JS
Yoon, HI
Cai, QY
Lin, CC
Park, IK
Xu, P
Dong, J
Kim, C
He, QC
Perng, RP
Kohno, T
Kweon, SS
Chen, CY
Vermeulen, RCH
Wu, JJ
Lim, WY
Chen, KC
Chow, WH
Ji, BT
Chan, JKC
Chu, MJ
Li, YJ
Yokota, J
Li, JH
Chen, HY
Xiang, YB
Yu, CJ
Kunitoh, H
Wu, GP
Jin, L
Lo, YL
Shiraishi, K
Chen, YH
Lin, HC
Wu, TC
Wong, MP
Wu, YL
Yang, PC
Zhou, BS
Shin, MH
Fraumeni, JF
Zheng, W
Lin, DX
Chanock, SJ
Rothman, N
Lan, Q
AF Machiela, Mitchell J.
Hsiung, Chao Agnes
Shu, Xiao-Ou
Seow, Wei Jie
Wang, Zhaoming
Matsuo, Keitaro
Hong, Yun-Chul
Seow, Adeline
Wu, Chen
Hosgood, H. Dean, III
Chen, Kexin
Wang, Jiu-Cun
Wen, Wanqing
Cawthon, Richard
Chatterjee, Nilanjan
Hu, Wei
Caporaso, Neil E.
Park, Jae Yong
Chen, Chien-Jen
Kim, Yeul Hong
Kim, Young Tae
Landi, Maria Teresa
Shen, Hongbing
Lawrence, Charles
Burdett, Laurie
Yeager, Meredith
Chang, I-Shou
Mitsudomi, Tetsuya
Kim, Hee Nam
Chang, Gee-Chen
Bassig, Bryan A.
Tucker, Margaret
Wei, Fusheng
Yin, Zhihua
An, She-Juan
Qian, Biyun
Lee, Victor Ho Fun
Lu, Daru
Liu, Jianjun
Jeon, Hyo-Sung
Hsiao, Chin-Fu
Sung, Jae Sook
Kim, Jin Hee
Gao, Yu-Tang
Tsai, Ying-Huang
Jung, Yoo Jin
Guo, Huan
Hu, Zhibin
Hutchinson, Amy
Wang, Wen-Chang
Klein, Robert J.
Chung, Charles C.
Oh, In-Jae
Chen, Kuan-Yu
Berndt, Sonja I.
Wu, Wei
Chang, Jiang
Zhang, Xu-Chao
Huang, Ming-Shyan
Zheng, Hong
Wang, Junwen
Zhao, Xueying
Li, Yuqing
Choi, Jin Eun
Su, Wu-Chou
Park, Kyong Hwa
Sung, Sook Whan
Chen, Yuh-Min
Liu, Li
Kang, Chang Hyun
Hu, Lingmin
Chen, Chung-Hsing
Pao, William
Kim, Young-Chul
Yang, Tsung-Ying
Xu, Jun
Guan, Peng
Tan, Wen
Su, Jian
Wang, Chih-Liang
Li, Haixin
Sihoe, Alan Dart Loon
Zhao, Zhenhong
Chen, Ying
Choi, Yi Young
Hung, Jen-Yu
Kim, Jun Suk
Yoon, Ho-Il
Cai, Qiuyin
Lin, Chien-Chung
Park, In Kyu
Xu, Ping
Dong, Jing
Kim, Christopher
He, Qincheng
Perng, Reury-Perng
Kohno, Takashi
Kweon, Sun-Seog
Chen, Chih-Yi
Vermeulen, Roel C. H.
Wu, Junjie
Lim, Wei-Yen
Chen, Kun-Chieh
Chow, Wong-Ho
Ji, Bu-Tian
Chan, John K. C.
Chu, Minjie
Li, Yao-Jen
Yokota, Jun
Li, Jihua
Chen, Hongyan
Xiang, Yong-Bing
Yu, Chong-Jen
Kunitoh, Hideo
Wu, Guoping
Jin, Li
Lo, Yen-Li
Shiraishi, Kouya
Chen, Ying-Hsiang
Lin, Hsien-Chih
Wu, Tangchun
Wong, Maria Pik
Wu, Yi-Long
Yang, Pan-Chyr
Zhou, Baosen
Shin, Min-Ho
Fraumeni, Joseph F., Jr.
Zheng, Wei
Lin, Dongxin
Chanock, Stephen J.
Rothman, Nathaniel
Lan, Qing
TI Genetic variants associated with longer telomere length are associated
with increased lung cancer risk among never-smoking women in Asia: a
report from the female lung cancer consortium in Asia
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE association study; genetics; lung cancer; telomere length; genetic risk
score
ID MULTIPLEX QUANTITATIVE PCR; BLOOD; SENESCENCE; DISEASE; HEALTH; CELLS;
LOCI; DNA
AB Recent evidence from several relatively small nested case-control studies in prospective cohorts shows an association between longer telomere length measured phenotypically in peripheral white blood cell (WBC) DNA and increased lung cancer risk. We sought to further explore this relationship by examining a panel of seven telomere-length associated genetic variants in a large study of 5,457 never-smoking female Asian lung cancer cases and 4,493 never-smoking female Asian controls using data from a previously reported genome-wide association study. Using a group of 1,536 individuals with phenotypically measured telomere length in WBCs in the prospective Shanghai Women's Health study, we demonstrated the utility of a genetic risk score (GRS) of seven telomere-length associated variants to predict telomere length in an Asian population. We then found that GRSs used as instrumental variables to predict longer telomere length were associated with increased lung cancer risk (OR=1.51 (95% CI=1.34-1.69) for upper vs. lower quartile of the weighted GRS, p value=4.54 x 10(-14)) even after removing rs2736100 (p value=4.81 x 10(-3)), a SNP in the TERT locus robustly associated with lung cancer risk in prior association studies. Stratified analyses suggested the effect of the telomere-associated GRS is strongest among younger individuals. We found no difference in GRS effect between adenocarcinoma and squamous cell subtypes. Our results indicate that a genetic background that favors longer telomere length may increase lung cancer risk, which is consistent with earlier prospective studies relating longer telomere length with increased lung cancer risk.
What's new? The possibility for a relationship between telomere length and cancer is intriguing, but many questions remain, including whether short or long telomeres are involved. Here, a genetic risk score derived from seven telomere-length associated genetic variants revealed a positive association between telomere length and lung cancer risk in Asian women who never smoked. The genetic proxy was unaffected by reverse-causation bias or environmental exposures. The differences in telomere length captured by the variants could aid in the identification of biological mechanisms that underlie the association between longer telomere length and increased lung cancer risk.
C1 [Machiela, Mitchell J.; Seow, Wei Jie; Chatterjee, Nilanjan; Hu, Wei; Caporaso, Neil E.; Landi, Maria Teresa; Bassig, Bryan A.; Tucker, Margaret; Chung, Charles C.; Berndt, Sonja I.; Kim, Christopher; Chow, Wong-Ho; Ji, Bu-Tian; Fraumeni, Joseph F., Jr.; Chanock, Stephen J.; Rothman, Nathaniel; Lan, Qing] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Hsiung, Chao Agnes; Hsiao, Chin-Fu; Wang, Wen-Chang; Lo, Yen-Li; Chen, Ying-Hsiang; Lin, Hsien-Chih] Natl Hlth Res Inst, Inst Populat Hlth Sci, Zhunan, Taiwan.
[Shu, Xiao-Ou; Wen, Wanqing; Cai, Qiuyin; Zheng, Wei] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA.
[Shu, Xiao-Ou; Wen, Wanqing; Cai, Qiuyin; Zheng, Wei] Vanderbilt Univ, Med Ctr, Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
[Wang, Zhaoming; Burdett, Laurie; Yeager, Meredith; Hutchinson, Amy] NCI, Canc Genom Res Lab, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Matsuo, Keitaro] Aichi Canc Ctr, Res Inst, Div Epidemiol & Prevent, Nagoya, Aichi 464, Japan.
[Hong, Yun-Chul] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea.
[Seow, Adeline; Chen, Ying; Lim, Wei-Yen] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore.
[Wu, Chen; Chang, Jiang; Tan, Wen; Lin, Dongxin] Chinese Acad Med Sci, Canc Inst & Hosp, Dept Etiol & Carcinogenesis, Beijing 100730, Peoples R China.
[Wu, Chen; Chang, Jiang; Tan, Wen; Lin, Dongxin] Peking Union Med Coll, Beijing 100021, Peoples R China.
[Wu, Chen] Chinese Acad Med Sci, Canc Inst & Hosp, State Key Lab Mol Oncol, Beijing 100730, Peoples R China.
[Hosgood, H. Dean, III] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
[Chen, Kexin; Zheng, Hong; Li, Haixin] Med Univ Canc Inst & Hosp, Natl Clin Res Ctr Canc, Key Lab Canc Prevent & Therapy, Dept Epidemiol & Biostat, Tianjin, Peoples R China.
[Wang, Jiu-Cun; Lu, Daru; Zhao, Xueying; Zhao, Zhenhong; Wu, Junjie; Chen, Hongyan; Jin, Li] Fudan Univ, Sch Life Sci, Minist Educ, Key Lab Contemporary Anthropol, Shanghai 200433, Peoples R China.
[Wang, Jiu-Cun] Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Shanghai 200433, Peoples R China.
[Cawthon, Richard] Univ Utah, Dept Human Genet, Salt Lake City, UT USA.
[Park, Jae Yong] Kyungpook Natl Univ, Lung Canc Ctr, Med Ctr, Daegu, South Korea.
[Chen, Chien-Jen; Li, Yao-Jen] Genom Res Ctr, Taipei, Taiwan.
[Kim, Yeul Hong; Park, Kyong Hwa] Korea Univ, Coll Med, Anam Hosp, Dept Internal Med,Div Oncol Hematol, Seoul 136705, South Korea.
[Kim, Young Tae; Jung, Yoo Jin; Kang, Chang Hyun; Park, In Kyu] Seoul Natl Univ, Coll Med, Canc Res Inst, Dept Thorac & Cardiovasc Surg, Seoul, South Korea.
[Shen, Hongbing; Hu, Zhibin; Hu, Lingmin; Dong, Jing; Chu, Minjie] Nanjing Med Univ, Jiangsu Collaborat Innovat Ctr Canc Personalized, Nanjing, Jiangsu, Peoples R China.
[Shen, Hongbing; Hu, Zhibin; Hu, Lingmin; Dong, Jing; Chu, Minjie] Nanjing Med Univ, Sch Publ Hlth, Ctr Canc, Jiangsu Key Lab Canc Biomarkers Prevent & Treatme, Nanjing, Jiangsu, Peoples R China.
[Lawrence, Charles] Westat Corp, Rockville, MD USA.
[Chang, I-Shou; Chen, Chung-Hsing] Natl Hlth Res Inst, Natl Inst Canc Res, Zhunan, Taiwan.
[Mitsudomi, Tetsuya] Kinki Univ, Sch Med, Div Thorac Surg, Sayama, Osaka 589, Japan.
[Kim, Hee Nam] Chonnam Natl Univ, Ctr Creat Biomed Scientists, Gwangju, South Korea.
[Chang, Gee-Chen] Natl Yang Ming Univ, Sch Med, Dept Med, Taipei 112, Taiwan.
[Chang, Gee-Chen; Yang, Tsung-Ying; Chen, Kun-Chieh] Taichung Vet Gen Hosp, Div Chest Med, Dept Internal Med, Taichung, Taiwan.
[Bassig, Bryan A.] Yale Univ, Div Environm Hlth Sci, Sch Publ Hlth, New Haven, CT USA.
[Wei, Fusheng; Wu, Guoping] China Natl Environm Monitoring Ctr, Beijing, Peoples R China.
[Yin, Zhihua; Wu, Wei; Guan, Peng; He, Qincheng; Zhou, Baosen] China Med Univ, Sch Publ Hlth, Dept Epidemiol, Shenyang 110001, Peoples R China.
[An, She-Juan; Zhang, Xu-Chao; Su, Jian; Wu, Yi-Long] Guangdong Acad Med Sci, Guangdong Gen Hosp, Guangdong Prov Key Lab Translat Med Lung Canc, Guangdong Lung Canc Inst, Guangzhou, Guangdong, Peoples R China.
[Qian, Biyun] Shanghai Jiao Tong Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Shanghai 200030, Peoples R China.
[Lee, Victor Ho Fun] Univ Hong Kong, Li Ka Shing Fac Med, Dept Clin Oncol, Hong Kong, Hong Kong, Peoples R China.
[Liu, Jianjun] Genome Inst Singapore, Dept Human Genet, Singapore, Singapore.
[Liu, Jianjun] Anhui Med Univ, Sch Life Sci, Hefei, Peoples R China.
[Jeon, Hyo-Sung] Kyungpook Natl Univ, Mol Diagnost & Imaging Ctr, Daegu, South Korea.
[Hsiao, Chin-Fu] Natl Hlth Res Inst, Taiwan Lung Canc Tissue Specimen Informat Resourc, Zhunan, Taiwan.
[Sung, Jae Sook] Korea Univ, Canc Res Inst, Seoul, South Korea.
[Kim, Jin Hee] Seoul Natl Univ, Grad Sch Publ Hlth, Dept Environm Hlth, Seoul, South Korea.
[Gao, Yu-Tang] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
[Tsai, Ying-Huang] Chang Gung Mem Hosp, Dept Resp Thearpy, Chiayi, Taiwan.
[Guo, Huan; Wu, Tangchun] Huazhong Univ Sci & Technol, Inst Occupat Med, Wuhan 430074, Peoples R China.
[Guo, Huan; Wu, Tangchun] Huazhong Univ Sci & Technol, Sch Publ Hlth, Minist Educ, Key Lab Environm & Hlth, Wuhan 430074, Peoples R China.
[Klein, Robert J.] Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY 10029 USA.
[Oh, In-Jae; Kim, Young-Chul] Chonnam Natl Univ, Hwasun Hosp, Lung & Esophageal Canc Clin, Hwasun Eup, South Korea.
[Oh, In-Jae; Kim, Young-Chul] Chonnam Natl Univ, Sch Med, Dept Internal Med, Gwangju, South Korea.
[Chen, Kuan-Yu; Yu, Chong-Jen] Natl Taiwan Univ Hosp, Dept Internal Med, Taipei 100, Taiwan.
[Huang, Ming-Shyan; Hung, Jen-Yu] Kaohsiung Med Univ, Sch Med, Kaohsiung Med Univ Hosp, Dept Internal Med, Kaohsiung, Taiwan.
[Wang, Junwen] Univ Hong Kong, Li Ka Shing Fac Med, Ctr Genom Sci, Hong Kong, Hong Kong, Peoples R China.
[Wang, Junwen] Univ Hong Kong, Li Ka Shing Fac Med, Dept Biochem, Hong Kong, Hong Kong, Peoples R China.
[Li, Yuqing] Canc Prevent Inst Calif, Fremont, CA USA.
[Choi, Jin Eun; Choi, Yi Young] Kyungpook Natl Univ, Med Ctr, Canc Res Ctr, Daegu, South Korea.
[Su, Wu-Chou; Lin, Chien-Chung] Cheng Kung Univ, Natl Coll Med, Natl Cheng Kung Univ Hosp, Dept Internal Med,Canc Ctr, Tainan, Taiwan.
[Sung, Sook Whan] Seoul St Marys Hosp, Dept Thorac & Cardiovasc Surg, Seoul, South Korea.
[Chen, Yuh-Min; Perng, Reury-Perng] Taipei Vet Gen Hosp, Dept Chest Med, Taipei, Taiwan.
[Chen, Yuh-Min] Taipei Med Univ, Taipei Canc Ctr, Taipei, Taiwan.
[Liu, Li] Huazhong Univ Sci & Technol, Union Hosp, Ctr Canc, Wuhan 430074, Peoples R China.
[Pao, William] Vanderbilt Univ, Med Ctr, Div Hematol & Oncol, Nashville, TN USA.
[Xu, Jun] Univ Hong Kong, Sch Publ Hlth, Hong Kong, Hong Kong, Peoples R China.
[Wang, Chih-Liang] Chang Gung Mem Hosp, Dept Pulm & Crit Care, Taoyuan, Taiwan.
[Sihoe, Alan Dart Loon] Queen Mary Hosp, Div Cardiothorac Surg, Dept Surg, Hong Kong, Hong Kong, Peoples R China.
[Kim, Jun Suk] Korea Univ, Coll Med, Guro Hosp, Dept Internal Med,Div Med Oncol, Seoul 136705, South Korea.
[Yoon, Ho-Il] Seoul Natl Univ, Bundang Hosp, Dept Internal Med, Songnam, South Korea.
[Xu, Ping] Staff Worker Hosp, Wuhan Iron & Steel Corp, Dept Oncol, Wuhan, Peoples R China.
[Kohno, Takashi; Yokota, Jun; Shiraishi, Kouya] Natl Canc Ctr, Res Inst, Div Genome Biol, Tokyo 104, Japan.
[Kweon, Sun-Seog] Chonnam Natl Univ, Jeonnam Reg Canc Ctr, Hwasun Hosp, Hwasun Eup, South Korea.
[Kweon, Sun-Seog; Shin, Min-Ho] Chonnam Natl Univ, Sch Med, Dept Prevent Med, Gwangju, South Korea.
[Chen, Chih-Yi] Chung Shan Med Univ, Chung Shan Med Univ Hosp, Inst Med, Div Thorac Surg, Taichung, Taiwan.
[Vermeulen, Roel C. H.] Univ Utrecht, Div Environm Epidemiol, IRAS, Utrecht, Netherlands.
[Chan, John K. C.] Queen Elizabeth Hosp, Dept Pathol, Hong Kong, Hong Kong, Peoples R China.
[Yokota, Jun] IMPPC, Barcelona, Spain.
[Li, Jihua] Qujing Ctr Dis Control & Prevent, Sanjiangdadao, Qujing, Peoples R China.
[Xiang, Yong-Bing] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Epidemiol,Shanghai Canc Inst, Shanghai 200030, Peoples R China.
[Kunitoh, Hideo] Japanese Red Cross Med Ctr, Dept Med Oncol, Tokyo, Japan.
[Wong, Maria Pik] Univ Hong Kong, Li Ka Shing Fac Med, Dept Pathol, Hong Kong, Hong Kong, Peoples R China.
[Yang, Pan-Chyr] Natl Taiwan Univ, Coll Med, Dept Internal Med, Taipei, Taiwan.
RP Machiela, MJ (reprint author), Adv Technol Ctr, Rm 225,8717 Grovemont Circle, Bethesda, MD 20892 USA.
EM mitchell.machiela@nih.gov
RI Chang, I-Shou/D-2084-2010; Hsiao, Chin-Fu/E-3993-2010; Chen,
Chien-Jen/C-6976-2008; Jin, Li/C-1468-2009; Wang, Junwen/D-3700-2011;
Vermeulen, Roel/F-8037-2011;
OI Jin, Li/0000-0002-4546-2415; Yu, Chong-Jen/0000-0001-5664-9392; Matsuo,
Keitaro/0000-0003-1761-6314; Wang, Junwen/0000-0002-4432-4707;
Vermeulen, Roel/0000-0003-4082-8163; Mitsudomi,
Tetsuya/0000-0001-9860-8505
FU Ministry of Health [201002007]; Ministry of Science and Technology
[2011BAI09B00]; National S&T Major Special Project [2011ZX09102-010-01];
China National High-Tech Research and Development Program [2012AA02A517,
2012AA02A518, 2009AA022705]; National Science Foundation of China
[30890034]; National Basic Research Program [2012CB944600]; Scientific
and Technological Support Plans from Jiangsu Province [BE2010715];
Foundation of Guangdong Science and Technology Department
[2006B60101010, 2007A032000002, 2011A030400010]; Guangzhou Science and
Information Technology Bureau [2011Y2-00014]; Chinese Lung Cancer
Research Foundation; National Natural Science Foundation [81101549];
Natural Science Foundation of Guangdong Province [S2011010000792];
National Research Program on Genomic Medicine in Taiwan
[DOH98-TD-G-111-015]; National Research Program for Biopharmaceuticals
in Taiwan [DOH 100-TD-PB-111-TM013, MOST 103-2325-B-400-011]; National
Science Council, Taiwan [NSC 100-2319-B-400-001]; National Medical
Research Council Singapore [NMRC/0897/2004, NMRC/1075/2006]; Agency for
Science, Technology and Research; General Research Fund of Research
Grant Council, Hong Kong [781511M, 17121414M]; National Science
Foundation, China [91229105]; Scientific Research on Priority Areas and
on Innovative Area from the Ministry of Education, Science, Sports,
Culture and Technology of Japan [NCI R01-CA121210]; National Key Basic
Research Program [2011CB503805]; National Research Foundation of Korea
[NRF-2014R1A2A2A05003665]; Ministry of Health & Welfare, Republic of
Korea [0720550-2, A010250]; National Key Basic Research and Development
Program [2011CB503800]; National Nature Science Foundation of China
[81102194]; Liaoning Provincial Department of Education [LS2010168];
China Medical Board [00726]; National Institutes of Health [R37
CA70867]; National Cancer Institute Intramural Research Program [N02
CP1101066]
FX Grant sponsor: Ministry of Health); Grant number: 201002007; Grant
sponsor: Ministry of Science and Technology; Grant number: 2011BAI09B00;
Grant sponsor: National S&T Major Special Project; Grant number:
2011ZX09102-010-01; Grant sponsor: China National High-Tech Research and
Development Program; Grant numbers: 2012AA02A517, 2012AA02A518; Grant
sponsor: National Science Foundation of China; Grant number: 30890034;
Grant sponsor: National Basic Research Program; Grant number:
2012CB944600; Grant sponsor: Scientific and Technological Support Plans
from Jiangsu Province; Grant number: BE2010715; Grant sponsor:
Foundation of Guangdong Science and Technology Department); Grant
numbers: 2006B60101010, 2007A032000002, 2011A030400010; Grant sponsor:
Guangzhou Science and Information Technology Bureau; Grant number:
2011Y2-00014; Grant sponsor: Chinese Lung Cancer Research Foundation,
National Natural Science Foundation; Grant number: 81101549; Grant
sponsor: Natural Science Foundation of Guangdong Province; Grant number:
S2011010000792; Grant sponsor: National Research Program on Genomic
Medicine in Taiwan); Grant number: DOH98-TD-G-111-015; Grant sponsor:
National Research Program for Biopharmaceuticals in Taiwan; Grant
numbers: DOH 100-TD-PB-111-TM013, MOST 103-2325-B-400-011; Grant
sponsor: National Science Council, Taiwan; Grant number: NSC
100-2319-B-400-001; Grant sponsor: National Medical Research Council
Singapore; Grant number: NMRC/0897/2004, NMRC/1075/2006; Grant sponsor:
Agency for Science, Technology and Research; Grant sponsor: General
Research Fund of Research Grant Council, Hong Kong); Grant numbers:
781511M, 17121414M; Grant sponsor: National Science Foundation, China;
Grant number: 91229105; Grant sponsor: Scientific Research on Priority
Areas and on Innovative Area from the Ministry of Education, Science,
Sports, Culture and Technology of Japan; Grant number: NCI R01-CA121210;
Grant sponsor: China National High-Tech Research and Development
Program; Grant number: 2009AA022705; Grant sponsor: National Key Basic
Research Program; Grant number: 2011CB503805; Grant sponsor: National
Research Foundation of Korea; Grant number: NRF-2014R1A2A2A05003665;
Grant sponsor: Ministry of Health & Welfare, Republic of Korea; Grant
numbers: 0720550-2, A010250; Grant sponsor: National Key Basic Research
and Development Program); Grant number: 2011CB503800; Grant sponsor:
National Nature Science Foundation of China); Grant number: 81102194;
Grant sponsor: Liaoning Provincial Department of Education; Grant
number: LS2010168; Grant sponsor: China Medical Board; Grant number:
00726; Grant sponsor: National Institutes of Health); Grant number: R37
CA70867; Grant sponsor: National Cancer Institute Intramural Research
Program; Grant number: N02 CP1101066
NR 32
TC 14
Z9 14
U1 3
U2 49
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 JUL 15
PY 2015
VL 137
IS 2
BP 311
EP 319
DI 10.1002/ijc.29393
PG 9
WC Oncology
SC Oncology
GA CH8LJ
UT WOS:000354287600007
PM 25516442
ER
PT J
AU Edefonti, V
Hashibe, M
Parpinel, M
Turati, F
Serraino, D
Matsuo, K
Olshan, AF
Zevallos, JP
Winn, DM
Moysich, K
Zhang, ZF
Morgenstern, H
Levi, F
Kelsey, K
McClean, M
Bosetti, C
Galeone, C
Schantz, S
Yu, GP
Boffetta, P
Lee, YC
Chuang, SC
La Vecchia, C
Decarli, A
AF Edefonti, Valeria
Hashibe, Mia
Parpinel, Maria
Turati, Federica
Serraino, Diego
Matsuo, Keitaro
Olshan, Andrew F.
Zevallos, Jose P.
Winn, Deborah M.
Moysich, Kirsten
Zhang, Zuo-Feng
Morgenstern, Hal
Levi, Fabio
Kelsey, Karl
McClean, Michael
Bosetti, Cristina
Galeone, Carlotta
Schantz, Stimson
Yu, Guo-Pei
Boffetta, Paolo
Amy Lee, Yuan-Chin
Chuang, Shu-Chun
La Vecchia, Carlo
Decarli, Adriano
TI Natural vitamin C intake and the risk of head and neck cancer: A pooled
analysis in the International Head and Neck Cancer Epidemiology
Consortium
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE head and neck cancer; INHANCE; laryngeal cancer; oral and pharyngeal
cancer; vitamin C
ID UPPER-AERODIGESTIVE TRACT; FOOD-FREQUENCY QUESTIONNAIRE; SQUAMOUS-CELL
CARCINOMA; TOTAL-ENERGY-INTAKE; PHARYNGEAL CANCER; LARYNGEAL-CANCER;
VEGETABLE INTAKE; PROSPECTIVE COHORT; DIETARY PATTERNS; ABSOLUTE INTAKE
AB Evidence of associations between single nutrients and head and neck cancer (HNC) is still more limited and less consistent than that for fruit and vegetables. However, clarification of the protective mechanisms of fruit and vegetables is important to our understanding of HNC etiology. We investigated the association between vitamin C intake from natural sources and cancer of the oral cavity/pharynx and larynx using individual-level pooled data from ten case-control studies (5,959 cases and 12,248 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. After harmonization of study-specific exposure information via the residual method, adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using unconditional multiple logistic regression models on quintile categories of 'non-alcohol energy-adjusted' vitamin C intake. In the presence of heterogeneity of the estimated ORs among studies, we derived those estimates from generalized linear mixed models. Higher intakes of vitamin C were inversely related to oral and pharyngeal (OR=0.54, 95% CI: 0.45-0.65, for the fifth quintile category versus the first one, p for trend<0.001) and laryngeal cancers (OR=0.52, 95% CI: 0.40-0.68, p for trend=0.006), although in the presence of heterogeneity among studies for both sites. Inverse associations were consistently observed for the anatomical subsites of oral and pharyngeal cancer, and across strata of age, sex, education, body mass index, tobacco, and alcohol, for both cancer sites. The inverse association of vitamin C intake from foods with HNC may reflect a protective effect on these cancers; however, we cannot rule out other explanations.
What's new? A diet rich in fruits and vegetables is thought to offer protection against head and neck cancers (HNC). However, it has not been clear which specific nutrients might play a role in this effect. In this re-analysis of several previous studies, the authors found that a higher intake of vitamin C from natural sources was associated with a significantly lower risk of anatomical subsites of HNC.
C1 [Edefonti, Valeria; La Vecchia, Carlo; Decarli, Adriano] Univ Milan, Sez Stat Med & Biometria Giulio A Maccacaro, Dipartimento Sci Clin & Comunita, I-20133 Milan, Italy.
[Hashibe, Mia] Univ Utah, Sch Med, Dept Family & Prevent Med, Div Publ Hlth, Salt Lake City, UT 84112 USA.
[Hashibe, Mia] Univ Utah, Sch Med, Huntsman Canc Inst, Salt Lake City, UT USA.
[Parpinel, Maria] Univ Udine, Dept Med & Biol Sci, Inst Hyg & Epidemiol, I-33100 Udine, Italy.
[Turati, Federica; Bosetti, Cristina; Galeone, Carlotta] Ist Ric Farmacol Mario Negri, IRCCS, Dept Epidemiol, Milan, Italy.
[Turati, Federica; Decarli, Adriano] Fdn IRCSS Ist Nazl Tumori Milano, SC Stat Med Biometria & Bioinformat, Milan, Italy.
[Serraino, Diego] IRCCS, CRO Aviano Natl Canc Inst, Unit Epidemiol & Biostat, Aviano, Italy.
[Matsuo, Keitaro] Kyushu Univ, Fac Med Sci, Dept Prevent Med, Kyushu, Japan.
[Olshan, Andrew F.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Olshan, Andrew F.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Zevallos, Jose P.] Univ N Carolina, Dept Otolaryngol Head & Neck Surg, Chapel Hill, NC USA.
[Winn, Deborah M.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Moysich, Kirsten] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA.
[Moysich, Kirsten] Roswell Pk Canc Inst, Dept Immunol, Buffalo, NY 14263 USA.
[Zhang, Zuo-Feng] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA.
[Morgenstern, Hal] Univ Michigan, Sch Publ Hlth, Dept Epidemiol & Environm Hlth Sci, Ann Arbor, MI 48109 USA.
[Morgenstern, Hal] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
[Levi, Fabio] Univ Lausanne Hosp, Inst Social & Prevent Med IUMSP, Canc Epidemiol Unit, Lausanne, Switzerland.
[Kelsey, Karl] Brown Univ, Dept Pathol & Lab Med, Providence, RI 02912 USA.
[Kelsey, Karl] Brown Univ, Dept Epidemiol, Providence, RI 02912 USA.
[McClean, Michael] Boston Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA.
[Schantz, Stimson] New York Eye & Ear Infirm, Dept Otolaryngol, New York, NY 10003 USA.
[Yu, Guo-Pei] Peking Univ, Med Informat Ctr, Beijing, Peoples R China.
[Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA.
[Amy Lee, Yuan-Chin] Univ Utah, Sch Med, Dept Family & Prevent Med, Div Publ Hlth, Salt Lake City, UT 84112 USA.
[Chuang, Shu-Chun] Natl Hlth Res Inst, Inst Populat Hlth Sci, Miaoli, Taiwan.
RP Edefonti, V (reprint author), Univ Milan, Sez Stat Med & Biometria Giulio A Maccacaro, Dipartimento Sci Clin & Comunita, Via Venezian 1, I-20133 Milan, Italy.
EM valeria.edefonti@unimi.it
RI Decarli, Adriano/C-3129-2017; McClean, Michael/J-2934-2015; Turati,
Federica/K-3841-2016; Parpinel, Maria/B-1605-2012
OI Decarli, Adriano/0000-0003-1451-8292; Serraino,
Diego/0000-0003-0565-8920; La Vecchia, Carlo/0000-0003-1441-897X;
EDEFONTI, VALERIA CARLA/0000-0002-1995-1477; Turati,
Federica/0000-0002-5841-5773; Matsuo, Keitaro/0000-0003-1761-6314;
Parpinel, Maria/0000-0003-1309-4467
FU National Cancer Institute (NCI) [R03CA113157, NIDCR R03DE016611]; Swiss
Research Against Cancer; Swiss Research Against Cancer/Oncosuisse
[KFS-700, OCS-1633]; NIH [P50CA090388, R01DA011386, R03CA077954,
T32CA009142, U01CA096134, R21ES011667, R01CA078609, R01CA100679,
R01CA051845]; Scientific Research Grant from the Ministry of Education,
Science, Sports, Culture and Technology of Japan [17015052]; Ministry of
Health, Labor and Welfare of Japan [H20-002]; Italian Ministry of
Education [PRIN 2009 X8YCBN]; Italian Association for Research on Cancer
(AIRC); Italian League Against Cancer; Italian Ministry of Research;
Alper Research Program for Environmental Genomics of the UCLA Jonsson
Comprehensive Cancer Center; Intramural Program of the NCI, NIH, United
States; Italian Foundation for Cancer Research (FIRC)
FX Grant sponsor: National Cancer Institute (NCI); Grant numbers:
R03CA113157, NIDCR R03DE016611; Grant sponsor: Swiss Research Against
Cancer and the Swiss Research Against Cancer/Oncosuisse; Grant numbers:
KFS-700, OCS-1633; Grant sponsor: NIH; Grant numbers: P50CA090388,
R01DA011386, R03CA077954, T32CA009142, U01CA096134, R21ES011667,
R01CA078609, R01CA100679, R01CA051845; Grant sponsor: Scientific
Research Grant from the Ministry of Education, Science, Sports, Culture
and Technology of Japan; Grant number: 17015052; Grant sponsor: Ministry
of Health, Labor and Welfare of Japan; Grant number: H20-002; Grant
sponsor: Italian Ministry of Education; Grant number: PRIN 2009 X8YCBN;
Grant sponsors: Italian Association for Research on Cancer (AIRC);
Italian League Against Cancer; Italian Ministry of Research; Alper
Research Program for Environmental Genomics of the UCLA Jonsson
Comprehensive Cancer Center; The Intramural Program of the NCI, NIH,
United States; Italian Foundation for Cancer Research (FIRC)
NR 89
TC 5
Z9 6
U1 2
U2 18
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 JUL 15
PY 2015
VL 137
IS 2
BP 448
EP 462
DI 10.1002/ijc.29388
PG 15
WC Oncology
SC Oncology
GA CH8LJ
UT WOS:000354287600019
PM 25627906
ER
PT J
AU Dettmer, AM
Rosenberg, KL
Suomi, SJ
Meyer, JS
Novak, MA
AF Dettmer, Amanda M.
Rosenberg, Kendra L.
Suomi, Stephen J.
Meyer, Jerrold S.
Novak, Melinda A.
TI Associations between Parity, Hair Hormone Profiles during Pregnancy and
Lactation, and Infant Development in Rhesus Monkeys (Macaca mulatta)
SO PLOS ONE
LA English
DT Article
ID EXTREMELY PRETERM INFANTS; MATERNAL CORTISOL-LEVELS; DAIRY-COWS;
LUTEINIZING-HORMONE; PROGESTERONE REPLACEMENT; STEROID CONCENTRATIONS;
COGNITIVE-DEVELOPMENT; POSTNATAL ESTRADIOL; PSYCHOSOCIAL STRESS;
NONHUMAN-PRIMATES
AB Studies examining hormones throughout pregnancy and lactation in women have been limited to single, or a few repeated, short-term measures of endocrine activity. Furthermore, potential differences in chronic hormonal changes across pregnancy/lactation between first-time and experienced mothers are not well understood, especially as they relate to infant development. Hormone concentrations in hair provide long-term assessments of hormone production, and studying these measures in non-human primates allows for repeated sampling under controlled conditions that are difficult to achieve in humans. We studied hormonal profiles in the hair of 26 female rhesus monkeys (Macaca mulatta, n=12 primiparous), to determine the influences of parity on chronic levels of cortisol ( hair cortisol concentration, HCC) and progesterone (hair progesterone concentration, HPC) during early-to mid-pregnancy (PREG1), in late pregnancy/early lactation (PREG2/LACT1), and in peak lactation (LACT2). We also assessed infants' neurobehavioral development across the first month of life. After controlling for age and stage of pregnancy at the first hair sampling period, we found that HCCs overall peaked in PREG2/LACT1 (p=0.02), but only in primiparous monkeys (p<0.001). HPCs declined across pregnancy and lactation for all monkeys (p<0.01), and primiparous monkeys had higher HPCs overall than multiparous monkeys (p=0.02). Infants of primiparous mothers had lower sensorimotor reflex scores (p=0.02) and tended to be more irritable (p=0.05) and less consolable (p=0.08) in the first month of life. Moreover, across all subjects, HCCs in PREG2/LACT1 were positively correlated with irritability (r((s))=0.43, p=0.03) and negatively correlated with sensorimotor scores (r((s))=-0.41, p=0.04). Together, the present results indicate that primiparity influences both chronic maternal hormonal profiles and infant development. These effects may, in part, reflect differential reproductive and maternal effort in mothers with varied caretaking experience. In addition, infant exposure to relatively higher levels of maternal cortisol during the late fetal and early postnatal periods is predictive of poorer developmental outcomes.
C1 [Dettmer, Amanda M.; Suomi, Stephen J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Comparat Ethol Lab, NIH, Poolesville, MD 20837 USA.
[Rosenberg, Kendra L.; Meyer, Jerrold S.; Novak, Melinda A.] Univ Massachusetts, Dept Psychol & Brain Sci, Amherst, MA USA.
RP Dettmer, AM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Comparat Ethol Lab, NIH, Poolesville, MD 20837 USA.
EM dettmera@mail.nih.gov
OI Meyer, Jerrold/0000-0002-8382-7075
FU Eunice Kennedy Shriver National Institute of Child Health & Human
Development Division of Intramural Research Grant [HD001106]; National
Institutes of Health [OD011180]
FX SJS: Eunice Kennedy Shriver National Institute of Child Health & Human
Development Division of Intramural Research Grant #HD001106
https://dir.nichd.nih.gov/dirweb/home.html. MAN: National Institutes of
Health Grant #OD011180
http://www.nih.gov/about/almanac/organization/NCRR.htm.
NR 93
TC 4
Z9 4
U1 3
U2 18
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 JUL 14
PY 2015
VL 10
IS 7
AR e0131692
DI 10.1371/journal.pone.0131692
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN1QN
UT WOS:000358194900021
PM 26172048
ER
PT J
AU Drgonova, J
Walther, D
Singhal, S
Johnson, K
Kessler, B
Troncoso, J
Uhl, GR
AF Drgonova, Jana
Walther, Donna
Singhal, Sulabh
Johnson, Kennedy
Kessler, Brice
Troncoso, Juan
Uhl, George R.
TI Altered CSMD1 Expression Alters Cocaine-Conditioned Place Preference:
Mutual Support for a Complex Locus from Human and Mouse Models
SO PLOS ONE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; SMOKING-CESSATION SUCCESS; RISK VARIANT
RS10503253; MOLECULAR-GENETICS; NICOTINE REPLACEMENT; SCHIZOPHRENIA;
ADDICTION; MICE; DEPENDENCE; TRIAL
AB The CUB and sushi multiple domains 1 (CSMD1) gene harbors signals provided by clusters of nearby SNPs with 10(-2) > p > 10(-8) associations in genome wide association (GWAS) studies of addiction-related phenotypes. A CSMD1 intron 3 SNP displays p < 10(-8) association with schizophrenia and more modest associations with individual differences in performance on tests of cognitive abilities. CSDM1 encodes a cell adhesion molecule likely to influence development, connections and plasticity of brain circuits in which it is expressed. We tested association between CSMD1 genotypes and expression of its mRNA in postmortem human brains (n = 181). Expression of CSMD1 mRNA in human postmortem cerebral cortical samples differs 15-25%, in individuals with different alleles of simple sequence length and SNP polymorphisms located in the gene's third/ fifth introns, providing nominal though not Bonferroni-corrected significance. These data support mice with altered CSMD1 expression as models for common human CSMD1 allelic variation. We tested baseline and/ or cocaine-evoked addiction, emotion, motor and memory-related behaviors in +/- and -/-csmd1 knockout mice on mixed and on C57-backcrossed genetic backgrounds. Initial csmd1 knockout mice on mixed genetic backgrounds displayed a variety of coat colors and sizable individual differences in responses during behavioral testing. Backcrossed mice displayed uniform black coat colors. Cocaine conditioned place preference testing revealed significant influences of genotype (p = 0.02). Homozygote knockouts displayed poorer performance on aspects of the Morris water maze task. They displayed increased locomotion in some, though not all, environments. The combined data thus support roles for common level-of-expression CSMD1 variation in a drug reward phenotype relevant to addiction and in cognitive differences that might be relevant to schizophrenia. Mouse model results can complement data from human association findings of modest magnitude that identify likely polygenic influences.
C1 [Drgonova, Jana; Walther, Donna; Singhal, Sulabh; Johnson, Kennedy; Kessler, Brice] NIDA, Mol Nuropsychiatry Res Branch, NIH IRP, Baltimore, MD 21224 USA.
[Troncoso, Juan] Johns Hopkins Sch Med, Div Neuropathol, Baltimore, MD USA.
[Uhl, George R.] New Mexico VA Healthcare Syst, Off Res Dev, Albuquerque, NM 87108 USA.
RP Uhl, GR (reprint author), New Mexico VA Healthcare Syst, Off Res Dev, Albuquerque, NM 87108 USA.
EM george.uhl@va.gov
FU National Institutes on Drug Abuse Intramural Research Program
FX Funding was provided by National Institutes on Drug Abuse Intramural
Research Program. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 38
TC 0
Z9 0
U1 3
U2 42
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 JUL 14
PY 2015
VL 10
IS 7
AR e0120908
DI 10.1371/journal.pone.0120908
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN1QN
UT WOS:000358194900001
PM 26171607
ER
PT J
AU Tagliabue, E
Fargnoli, MC
Gandini, S
Maisonneuve, P
Liu, F
Kayser, M
Nijsten, T
Han, J
Kumar, R
Gruis, NA
Ferrucci, L
Branicki, W
Dwyer, T
Blizzard, L
Helsing, P
Autier, P
Garcia-Borron, JC
Kanetsky, PA
Landi, MT
Little, J
Newton-Bishop, J
Sera, F
Raimondi, S
AF Tagliabue, E.
Fargnoli, M. C.
Gandini, S.
Maisonneuve, P.
Liu, F.
Kayser, M.
Nijsten, T.
Han, J.
Kumar, R.
Gruis, N. A.
Ferrucci, L.
Branicki, W.
Dwyer, T.
Blizzard, L.
Helsing, P.
Autier, P.
Garcia-Borron, J. C.
Kanetsky, P. A.
Landi, M. T.
Little, J.
Newton-Bishop, J.
Sera, F.
Raimondi, S.
CA M-SKIP Study Grp
TI MC1R gene variants and non-melanoma skin cancer: a pooled-analysis from
the M-SKIP project
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE pooled-analysis; pigmentation genes; genetic epidemiology; basal cell
carcinoma; squamous cell carcinoma
ID MELANOCORTIN 1 RECEPTOR; BASAL-CELL CARCINOMA; CUTANEOUS MELANOMA; RED
HAIR; ULTRAVIOLET-RADIATION; HUMAN MELANOCYTES; DNA-DAMAGE; RISK;
POLYMORPHISM; POPULATION
AB Background: The melanocortin-1-receptor (MC1R) gene regulates human pigmentation and is highly polymorphic in populations of European origins. The aims of this study were to evaluate the association between MC1R variants and the risk of non-melanoma skin cancer (NMSC), and to investigate whether risk estimates differed by phenotypic characteristics.
Methods: Data on 3527 NMSC cases and 9391 controls were gathered through the M-SKIP Project, an international pooled-analysis on MC1R, skin cancer and phenotypic characteristics. We calculated summary odds ratios (SOR) with random-effect models, and performed stratified analyses.
Results: Subjects carrying at least one MC1R variant had an increased risk of NMSC overall, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC): SOR (95% CI) were 1.48 (1.24-1.76), 1.39 (1.15-1.69) and 1.61 (1.35-1.91), respectively. All of the investigated variants showed positive associations with NMSC, with consistent significant results obtained for V60L, D84E, V92M, R151C, R160W, R163Q and D294H: SOR (95% CI) ranged from 1.42 (1.19-1.70) for V60L to 2.66 (1.06-6.65) for D84E variant. In stratified analysis, there was no consistent pattern of association between MC1R and NMSC by skin type, but we consistently observed higher SORs for subjects without red hair.
Conclusions: Our pooled-analysis highlighted a role of MC1R variants in NMSC development and suggested an effect modification by red hair colour phenotype.
C1 [Tagliabue, E.; Gandini, S.; Maisonneuve, P.; Raimondi, S.] European Inst Oncol, Div Epidemiol & Biostat, I-20141 Milan, Italy.
[Fargnoli, M. C.] Univ Aquila, Dept Dermatol, I-47100 Laquila, Italy.
[Liu, F.; Kayser, M.] Erasmus MC Univ Med Ctr, Dept Forens Mol Biol, NL-3000 DR Rotterdam, Netherlands.
[Nijsten, T.] Erasmus MC Univ Med Ctr, Dept Dermatol, NL-3000 DR Rotterdam, Netherlands.
[Han, J.] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA.
[Han, J.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Han, J.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA.
[Han, J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Kumar, R.] German Canc Res Ctr, Div Mol Genet Epidemiol, D-69120 Heidelberg, Germany.
[Gruis, N. A.] Leiden Univ Med Ctr, Dept Dermatol, NL-2300 RC Leiden, Netherlands.
[Ferrucci, L.] Yale Univ, Sch Publ Hlth, Yale Canc Ctr, Dept Chron Dis Epidemiol, New Haven, CT 06520 USA.
[Branicki, W.] Inst Forens Res, PL-31033 Krakow, Poland.
[Dwyer, T.] Royal Childrens Hosp, Murdoch Childrens Res Inst, Parkville, Vic 3052, Australia.
[Blizzard, L.] Univ Tasmania, Menzies Res Inst Tasmania, Hobart, Tas 7001, Australia.
[Helsing, P.] Oslo Univ Hosp, Dept Pathol, N-0027 Oslo, Norway.
[Autier, P.] Int Prevent Res Inst, F-69006 Lyon, France.
[Garcia-Borron, J. C.] Univ Murcia, Dept Biochem Mol Biol & Immunol, E-30100 Murcia, Spain.
[Kanetsky, P. A.] H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL 33612 USA.
[Landi, M. T.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Little, J.] Univ Ottawa, Sch Epidemiol Publ Hlth & Prevent Med, Ottawa, ON K1N 6N5, Canada.
[Newton-Bishop, J.] Univ Leeds, Inst Canc & Pathol, Sect Epidemiol & Biostat, Leeds LS9 7TF, W Yorkshire, England.
[Sera, F.] UCL Inst Child Hlth, London WC1N 1EH, England.
RP Raimondi, S (reprint author), European Inst Oncol, Div Epidemiol & Biostat, Via Ripamonti 435, I-20141 Milan, Italy.
EM sara.raimondi@ieo.it
RI Autier, Philippe/A-4402-2014; Raimondi, Sara/J-5236-2016; Liu,
Fan/B-8833-2013;
OI Gandini, Sara/0000-0002-1348-4548; Autier, Philippe/0000-0003-1538-5321;
Raimondi, Sara/0000-0003-4673-9049; Liu, Fan/0000-0001-9241-8161; Gruis,
Nelleke/0000-0002-5210-9150; Kumar, Rajiv/0000-0002-6093-0395; Berwick,
Marianne/0000-0001-5062-2180; Fargnoli, Maria
Concetta/0000-0002-7249-2556; Palmieri, Giuseppe/0000-0002-4350-2276;
Newton Bishop, Julia/0000-0001-9147-6802; Bowcock,
Anne/0000-0001-8691-9090; Maisonneuve, Patrick/0000-0002-5309-4704;
Puig, Susana/0000-0003-1337-9745; CARRERA, CRISTINA/0000-0003-1608-8820
FU Italian Association for Cancer Research [MFAG 11831]
FX This work was supported by the Italian Association for Cancer Research
(grant number: MFAG 11831). The M-SKIP study group consists of the
following members: Principal Investigator: Sara Raimondi (the European
Institute of Oncology, Milan, Italy); Advisory Committee members:
Philippe Autier (the International Prevention Research Institute, Lyon,
France), Maria Concetta Fargnoli (the University of L'Aquila, Italy),
Jose C Garcia-Borron (the University of Murcia, Spain), Jiali Han
(Brigham and Women's Hospital and Harvard Medical School, Boston, MA,
USA), Peter A Kanetsky (Department of Cancer Epidemiology, H. Lee
Moffitt Cancer Center and Research Institute, Tampa, FL, USA), Maria
Teresa Landi (the National Cancer Institute, NIH, Bethesda, MD, USA),
Julian Little (the University of Ottawa, Canada), Julia Newton-Bishop
(the University of Leeds, UK), Francesco Sera (the UCL Institute of
Child Health, London, UK); Consultants: Saverio Caini (ISPO, Florence,
Italy), Sara Gandini and Patrick Maisonneuve (the European Institute of
Oncology, Milan, Italy); Participant Investigators: Albert Hofman,
Manfred Kayser, Fan Liu, Tamar Nijsten and Andre G. Uitterlinden (the
Erasmus MC University Medical Center, Rotterdam, The Netherlands), Rajiv
Kumar and Dominique Scherer (the German Cancer Research Center,
Heidelberg, Germany), Eduardo Nagore (the Instituto Valenciano de
Oncologia, Valencia, Spain), Johan Hansson and Veronica Hoiom
(Karolinska Institutet, Stockholm, Sweden), Paola Ghiorzo and Lorenza
Pastorino (the University of Genoa, Italy), Nelleke A. Gruis and Jan
Nico Bouwes Bavinck (the Leiden University Medical Center, The
Netherlands), Paula Aguilera, Celia Badenas, Cristina Carrera, Josep
Malvehy, Miriam Potrony Mateu, Susana Puig, Joan Anton Puig-Butille,
Gemma Tell (the Hospital Clinic, IDIBAPS and CIBERER, Barcelona, Spain),
Terence Dwyer (the Murdoch Childrens Research Institute, Victoria,
Australia), Leigh Blizzard and Jennifer Cochrane (the Menzies Research
Institute Tasmania, Hobart, Australia), Ricardo Fernandez-de-Misa (the
Hospital Universitario Nuestra Senora de Candelaria, Santa Cruz de
Tenerife, Spain), Wojciech Branicki (the Institute of Forensic Research,
Krakow, Poland), Tadeusz Debniak (the Pomeranian Medical University,
Polabska, Poland), Niels Morling and Peter Johansen (the University of
Copenhagen, Denmark), Susan Mayne, Allen Bale, Brenda Cartmel and Leah
Ferrucci (the Yale School of Public Health and Medicine, New Haven, CT,
USA), Ruth Pfeiffer (the National Cancer Institute, NIH, Bethesda, MD,
USA), Giuseppe Palmieri (the Istituto di Chimica Biomolecolare, CNR,
Sassari, Italy), Gloria Ribas (the Fundacion Investigacion Clinico de
Valencia Instituto de Investigacion Sanitaria-INCLIVA, Spain), Alexander
Stratigos and Katerina Kypreou (the University of Athens, Andreas Sygros
Hospital, Athens, Greece), Anne Bowcock, Lynn Cornelius and M. Laurin
Council (the Washington University School of Medicine, St Louis, MO,
USA), Tomonori Motokawa (POLA Chemical Industries, Yokohama, Japan),
Sumiko Anno (the Shibaura Institute of Technology, Tokyo, Japan), Per
Helsing and Per Arne Andresen (the Oslo University Hospital, Norway),
Terence H. Wong (the University of Edinburgh, UK) and the GEM Study
Group.; Participants in the GEM Study Group are as follows: Coordinating
Center, Memorial Sloan-Kettering Cancer Center, New York, NY, USA:
Marianne Berwick (PI, currently at the University of New Mexico), Colin
Begg (Co-PI), Irene Orlow (Co-Investigator), Urvi Mujumdar (Project
Coordinator), Amanda Hummer (Biostatistician), Klaus Busam
(Dermatopathologist), Pampa Roy (Laboratory Technician), Rebecca
Canchola (Laboratory Technician), Brian Clas (Laboratory Technician),
Javiar Cotignola (Laboratory Technician), Yvette Monroe (Interviewer).
Study Centers: The University of Sydney and The Cancer Council New South
Wales, Sydney (Australia): Bruce Armstrong (PI), Anne Kricker (co-PI),
Melisa Litchfield (Study Coordinator). Menzies Centre for Population
Health Research, the University of Tasmania, Hobart (Australia): Terence
Dwyer (PI), Paul Tucker (Dermatopathologist), Nicola Stephens (Study
Coordinator). The British Columbia Cancer Agency, Vancouver (Canada):
Richard Gallagher (PI), Teresa Switzer (Coordinator). The Cancer Care
Ontario, Toronto (Canada): Loraine Marrett (PI), Beth Theis
(Co-Investigator), Lynn From (Dermatopathologist), Noori Chowdhury
(Coordinator), Louise Vanasse (Coordinator), Mark Purdue (Research
Officer). David Northrup (Manager for CATI). Centro per la Prevenzione
Oncologia Torino, Piemonte (Italy): Roberto Zanetti (PI), Stefano Rosso
(Data Manager), Carlotta Sacerdote (Coordinator). The University of
California, Irvine (USA): Hoda Anton-Culver (PI), Nancy Leighton
(Coordinator), Maureen Gildea (Data Manager). The University of
Michigan, Ann Arbor (USA): Stephen Gruber (PI), Joe Bonner (Data
Manager), Joanne Jeter (Coordinator). The New Jersey Department of
Health and Senior Services, Trenton (USA): Judith Klotz (PI), Homer
Wilcox (Co-PI), Helen Weiss (Coordinator). The University of North
Carolina, Chapel Hill (USA): Robert Millikan (PI), Nancy Thomas
(Co-Investigator), Dianne Mattingly (Coordinator), Jon Player
(Laboratory Technician), Chiu-Kit Tse (Data Analyst). The University of
Pennsylvania, Philadelphia, PA (USA): Timothy Rebbeck (PI), Peter
Kanetsky (Co-Investigator), Amy Walker (Laboratory Technician), Saarene
Panossian (Laboratory Technician). Consultants: Harvey Mohrenweiser, The
University of California, Irvine, Irvine, CA (USA); Richard Setlow, The
Brookhaven National Laboratory, Upton, NY (USA).
NR 51
TC 2
Z9 3
U1 2
U2 12
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
EI 1532-1827
J9 BRIT J CANCER
JI Br. J. Cancer
PD JUL 14
PY 2015
VL 113
IS 2
BP 354
EP 363
DI 10.1038/bjc.2015.231
PG 10
WC Oncology
SC Oncology
GA CM8JZ
UT WOS:000357947800021
PM 26103569
ER
PT J
AU Greenland, P
Lauer, MS
AF Greenland, Philip
Lauer, Michael S.
TI Cholesterol Lowering in 2015 Still Answering Questions About How and in
Whom
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID ATHEROSCLEROTIC CARDIOVASCULAR-DISEASE; RISK; PREVENTION; GUIDELINES;
PEOPLE; COHORT
C1 [Greenland, Philip] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA.
[Greenland, Philip] Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA.
[Lauer, Michael S.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
RP Greenland, P (reprint author), Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, 680 N Lake Shore Dr,Ste 1400, Chicago, IL 60611 USA.
EM p-greenland@northwestern.edu
NR 12
TC 6
Z9 7
U1 0
U2 5
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUL 14
PY 2015
VL 314
IS 2
BP 127
EP 128
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA CM7JI
UT WOS:000357867500010
PM 26172891
ER
PT J
AU Romero, R
Mahoney, MJ
AF Romero, Roberto
Mahoney, Maurice J.
TI Noninvasive Prenatal Testing and Detection of Maternal Cancer
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID DNA
C1 [Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,NIH, Bethesda, MD 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.
[Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA.
[Mahoney, Maurice J.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA.
[Mahoney, Maurice J.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA.
[Mahoney, Maurice J.] Yale Univ, Sch Med, Dept Obstet & Gynecol, New Haven, CT 06510 USA.
RP Romero, R (reprint author), Perinatol Res Branch, 3990 John R Rd,4 Brush S, Detroit, MI 48201 USA.
EM romeror@mail.nih.gov
FU Intramural NIH HHS
NR 15
TC 4
Z9 4
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUL 14
PY 2015
VL 314
IS 2
BP 131
EP 133
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA CM7JI
UT WOS:000357867500012
PM 26168080
ER
PT J
AU Pursnani, A
Massaro, JM
D'Agostino, RB
O'Donnell, CJ
Hoffmann, U
AF Pursnani, Amit
Massaro, Joseph M.
D'Agostino, Ralph B., Sr.
O'Donnell, Christopher J.
Hoffmann, Udo
TI Guideline-Based Statin Eligibility, Coronary Artery Calcification, and
Cardiovascular Events
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID ADULT TREATMENT PANEL; BLOOD CHOLESTEROL; CALCIUM; RISK; ASSOCIATION;
PROGRESSION; ACCURACY
AB IMPORTANCE The 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines for cholesterol management defined new eligibility criteria for statin therapy. However, it is unclear whether this approach improves identification of adults at higher risk of cardiovascular events.
OBJECTIVE To determine whether the ACC/AHA guidelines improve identification of individuals who develop incident cardiovascular disease (CVD) and/or have coronary artery calcification (CAC) compared with the National Cholesterol Education Program's 2004 Updated Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III) guidelines.
DESIGN, SETTING, AND PARTICIPANTS Longitudinal community-based cohort study, with participants for this investigation drawn from the offspring and third-generation cohorts of the Framingham Heart Study. Participants underwent multidetector computed tomography for CAC between 2002 and 2005 and were followed up for a median of 9.4 years for incident CVD.
EXPOSURES Statin eligibility was determined based on Framingham risk factors and low-density lipoprotein thresholds for ATP III, whereas the pooled cohort calculator was used for ACC/AHA.
MAIN OUTCOMES AND MEASURES The primary outcome was incident CVD (myocardial infarction, death due to coronary heart disease [CHD], or ischemic stroke). Secondary outcomes were CHD and CAC (as measured by the Agatston score).
RESULTS Among 2435 statin-naive participants (mean age, 51.3 [SD, 8.6] years; 56% female), 39%(941/2435) were statin eligible by ACC/AHA compared with 14%(348/2435) by ATP III (P<.001). There were 74 incident CVD events (40 nonfatal myocardial infarctions, 31 nonfatal ischemic strokes, and 3 fatal CHD events). Participants who were statin eligible by ACC/AHA had increased hazard ratios for incident CVD compared with those eligible by ATP III: 6.8 (95% CI, 3.8-11.9) vs 3.1 (95% CI, 1.9-5.0), respectively (P<001). Similar results were seen for CVD in participants with intermediate Framingham Risk Scores and for CHD. Participants who were newly statin eligible (n = 593 [24%]) had an incident CVD rate of 5.7%, yielding a number needed to treat of 39 to 58. Participants with CAC were more likely to be statin eligible by ACC/AHA than by ATP III: CAC score >0 (n = 1015): 63% vs 23%; CAC score >100 (n = 376): 80% vs 32%; and CAC score >300 (n = 186): 85% vs 34%(all P<.001). A CAC score of 0 identified a low-risk group among ACC/AHA statin-eligible participants (306/941 [33%]) with a CVD rate of 1.6%.
CONCLUSIONS AND RELEVANCE In this community-based primary prevention cohort, the ACC/AHA guidelines for determining statin eligibility, compared with the ATP III, were associated with greater accuracy and efficiency in identifying increased risk of incident CVD and subclinical coronary artery disease, particularly in intermediate-risk participants.
C1 [Pursnani, Amit; Hoffmann, Udo] Harvard Univ, Cardiac MR PET CT Program, Massachusetts Gen Hosp, Dept Radiol,Med Sch, Boston, MA 02114 USA.
[Pursnani, Amit] NorthShore Univ Hlth Syst, Div Cardiol, Evanston, IL USA.
[Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Massaro, Joseph M.; D'Agostino, Ralph B., Sr.; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Massaro, Joseph M.; D'Agostino, Ralph B., Sr.; O'Donnell, Christopher J.] Boston Univ, Framingham, MA USA.
[D'Agostino, Ralph B., Sr.] Boston Univ, Dept Math, Boston, MA 02215 USA.
[O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA.
[O'Donnell, Christopher J.; Hoffmann, Udo] Harvard Univ, Div Cardiol, Dept Med, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA.
RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, 100 Charles River Plaza,Ste 400, Boston, MA 02114 USA.
EM uhoffmann@mgh.harvard.edu
FU National Heart, Lung, and Blood Institute's Framingham Heart Study
[N01-HC-25195, HL076784, AG028321, HL070100, HL060040, HL080124,
HL071039, HL077447, HL107385]; National Institutes of Health [T32
HL076136]
FX This work was supported by the National Heart, Lung, and Blood
Institute's Framingham Heart Study (contracts N01-HC-25195, HL076784,
AG028321, HL070100, HL060040, HL080124, HL071039, HL077447, and
HL107385). Dr Pursnani was supported by National Institutes of Health
grant T32 HL076136.
NR 23
TC 40
Z9 40
U1 0
U2 4
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUL 14
PY 2015
VL 314
IS 2
BP 134
EP 141
DI 10.1001/jama.2015.7515
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA CM7JI
UT WOS:000357867500013
PM 26172893
ER
PT J
AU Osinusi, A
Townsend, K
Kottilil, S
AF Osinusi, Anu
Townsend, Kerry
Kottilil, Shyam
TI Drug-Drug Interactions in Patients Co-infected With HCV and HIV Reply
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Letter
ID TOXICITY
C1 [Osinusi, Anu; Kottilil, Shyam] Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA.
[Townsend, Kerry] NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA.
RP Kottilil, S (reprint author), Univ Maryland, Sch Med, Inst Human Virol, Div Clin Care & Res, Baltimore, MD 21201 USA.
EM skottilil@ihv.umaryland.edu
NR 5
TC 1
Z9 1
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUL 14
PY 2015
VL 314
IS 2
BP 186
EP 187
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA CM7JI
UT WOS:000357867500021
PM 26172900
ER
PT J
AU Fu, G
Batchelor, C
Dumontier, M
Hastings, J
Willighagen, E
Bolton, E
AF Fu, Gang
Batchelor, Colin
Dumontier, Michel
Hastings, Janna
Willighagen, Egon
Bolton, Evan
TI PubChemRDF: towards the semantic annotation of PubChem compound and
substance databases
SO JOURNAL OF CHEMINFORMATICS
LA English
DT Article
ID SYSTEMS CHEMICAL BIOLOGY; LINKED OPEN DATA; DATA INTEGRATION; DRUG
DISCOVERY; WEB; KNOWLEDGE; ONTOLOGY; CHEMINFORMATICS; FRAMEWORK;
ENTITIES
AB Background: PubChem is an open repository for chemical structures, biological activities and biomedical annotations. Semantic Web technologies are emerging as an increasingly important approach to distribute and integrate scientific data. Exposing PubChem data to Semantic Web services may help enable automated data integration and management, as well as facilitate interoperable web applications.
Description: This work, one of a series covering the PubChemRDF project, describes an approach to translate PubChem Substance and Compound information into Resource Description Framework (RDF) format. Basic examples are provided to demonstrate its use. The aim of this effort is to provide two new primary benefits to researchers in a cost-effective manner. Firstly, we aim to remove the inherent limitations of using the web-based resource PubChem by allowing a researcher to use readily available semantic technologies (namely, RDF triple stores and their corresponding SPARQL query engines) to query and analyze PubChem data on local computing resources. Secondly, this work intends to help improve data sharing, analysis, and integration of PubChem data to resources external to NCBI and across scientific domains, by means of the association of PubChem data to existing ontological frameworks, including CHEMical INFormation ontology, Semanticscience Integrated Ontology, and others.
Conclusions: With the goal of semantically describing information available in the PubChem archive, pre-existing ontological frameworks were used, rather than creating new ones. Semantic relationships between compounds and substances, chemical descriptors associated with compounds and substances, interrelationships between chemicals, as well as provenance and attribute metadata of substances are described.
C1 [Fu, Gang; Bolton, Evan] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
[Batchelor, Colin] Royal Soc Chem, Cambridge, England.
[Dumontier, Michel] Stanford Univ, Stanford Ctr Biomed Informat Res, Stanford, CA 94305 USA.
[Hastings, Janna] EMBL EBI, Hinxton, Cambs, England.
[Willighagen, Egon] Maastricht Univ, Dept Bioinformat BiGCaT, NUTRIM, Maastricht, Netherlands.
RP Fu, G (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
EM gang.fu@nih.gov
RI Trivedi, Kruti/E-7558-2015; Fu, Gang/F-8837-2016;
OI Fu, Gang/0000-0002-4860-8539; Hastings, Janna/0000-0002-3469-4923;
Batchelor, Colin/0000-0001-5985-7429; Willighagen,
Egon/0000-0001-7542-0286
FU Intramural Research Program of the National Library of Medicine, NIH
FX This research was supported [in part] by the Intramural Research Program
of the National Library of Medicine, NIH. Many thanks to the PubChem
team (including Paul Thiessen, Lianyi Han, Jane He, Siqian He) who
provided database API functions to retrieve data from Compound and
Substance databases.
NR 42
TC 5
Z9 5
U1 1
U2 10
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1758-2946
J9 J CHEMINFORMATICS
JI J. Cheminformatics
PD JUL 14
PY 2015
VL 7
AR 34
DI 10.1186/s13321-015-0084-4
PG 15
WC Chemistry, Multidisciplinary; Computer Science, Information Systems;
Computer Science, Interdisciplinary Applications
SC Chemistry; Computer Science
GA CM6FB
UT WOS:000357782400001
PM 26175801
ER
PT J
AU Mankodi, A
Grunseich, C
AF Mankodi, Ami
Grunseich, Christopher
TI Toe-extension myotonia in myotonic dystrophy type 1
SO NEUROLOGY
LA English
DT Editorial Material
C1 [Mankodi, Ami; Grunseich, Christopher] NINDS, Neurogenet Branch, Bethesda, MD 20892 USA.
RP Mankodi, A (reprint author), NINDS, Neurogenet Branch, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM ami.mankodi@nih.gov
FU Intramural NIH HHS
NR 2
TC 0
Z9 0
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD JUL 14
PY 2015
VL 85
IS 2
BP 203
EP 203
PG 1
WC Clinical Neurology
SC Neurosciences & Neurology
GA CM6NG
UT WOS:000357804900017
PM 26170401
ER
PT J
AU Singh, SK
Gellert, M
AF Singh, Samarendra K.
Gellert, Martin
TI Role of RAG1 autoubiquitination in V(D)J recombination
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE ubiquitin; immunoglobulin; diversification
ID UBIQUITIN LIGASE; PROTEINS; DNA; MECHANISM; TERMINUS; CLEAVAGE; DEFECTS;
REPAIR; SIGNAL
AB The variable domains of Ig and T-cell receptor genes in vertebrates are assembled from gene fragments by the V(D)J recombination process. The RAG1-RAG2 recombinase (RAG1/2) initiates this recombination by cutting DNA at the borders of recombination signal sequences (RSS) and their neighboring gene segments. The RAG1 protein is also known to contain a ubiquitin E3 ligase activity, located in an N-terminal region that is not strictly required for the basic recombination reaction but helps to regulate recombination. The isolated E3 ligase domain was earlier shown to ubiquitinate one site in a neighboring RAG1 sequence. Here we show that autoubiquitination of full-length RAG1 at this specific residue (K233) results in a large increase of DNA cleavage by RAG1/2. A mutational block of the ubiquitination site abolishes this effect and inhibits recombination of a test substrate in mouse cells. Thus, ubiquitination of RAG1, which can be promoted by RAG1's own ubiquitin ligase activity, plays a significant role in governing the level of V(D)J recombination activity.
C1 [Singh, Samarendra K.; Gellert, Martin] Natl Inst Diabet & Digest & Kidney Dis, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Gellert, M (reprint author), Natl Inst Diabet & Digest & Kidney Dis, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM gellert@helix.nih.gov
FU intramural research program of the National Institute of Diabetes and
Digestive and Kidney Diseases, National Institutes of Health
FX We thank Wei Yang for continuing valuable discussions throughout this
project. Our work was supported by the intramural research program of
the National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health.
NR 28
TC 2
Z9 2
U1 0
U2 4
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 14
PY 2015
VL 112
IS 28
BP 8579
EP 8583
DI 10.1073/pnas.1510464112
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CM7MU
UT WOS:000357878700036
PM 26124138
ER
PT J
AU Kehdy, FSG
Gouveia, MH
Machado, M
Magalhaes, WCS
Horimoto, AR
Horta, BL
Moreira, RG
Leal, TP
Scliar, MO
Soares-Souza, GB
Rodrigues-Soares, F
Araujo, GS
Zamudio, R
Anna, HPS
Santos, HC
Duarte, NE
Fiaccone, RL
Figueiredo, CA
Silva, TM
Costa, GNO
Beleza, S
Berg, DE
Cabrera, L
Debortoli, G
Duarte, D
Ghirotto, S
Gilman, RH
Goncalves, VF
Marrero, AR
Muniz, YC
Weissensteiner, H
Yeager, M
Rodrigues, LC
Barreto, ML
Lima-Costa, MF
Pereira, AC
Rodrigues, MR
Tarazona-Santos, E
AF Kehdy, Fernanda S. G.
Gouveia, Mateus H.
Machado, Moara
Magalhaes, Wagner C. S.
Horimoto, Andrea R.
Horta, Bernardo L.
Moreira, Rennan G.
Leal, Thiago P.
Scliar, Marilia O.
Soares-Souza, Giordano B.
Rodrigues-Soares, Fernanda
Araujo, Gilderlanio S.
Zamudio, Roxana
Anna, Hanaisa P. Sant
Santos, Hadassa C.
Duarte, Nubia E.
Fiaccone, Rosemeire L.
Figueiredo, Camila A.
Silva, Thiago M.
Costa, Gustavo N. O.
Beleza, Sandra
Berg, Douglas E.
Cabrera, Lilia
Debortoli, Guilherme
Duarte, Denise
Ghirotto, Silvia
Gilman, Robert H.
Goncalves, Vanessa F.
Marrero, Andrea R.
Muniz, Yara C.
Weissensteiner, Hansi
Yeager, Meredith
Rodrigues, Laura C.
Barreto, Mauricio L.
Lima-Costa, M. Fernanda
Pereira, Alexandre C.
Rodrigues, Maira R.
Tarazona-Santos, Eduardo
CA Brazilian EPIGEN Project Consortiu
TI Origin and dynamics of admixture in Brazilians and its effect on the
pattern of deleterious mutations
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE Latin America; population genetics; Salvador SCAALA; Bambul Cohort Study
of Ageing; Pelotas Birth Cohort Study
ID GENOME-WIDE ASSOCIATION; GENETIC-STRUCTURE; AFRICAN-AMERICANS; COHORT
PROFILE; POPULATION; ANCESTRY; COMMUNITY; STRATIFICATION; INDIVIDUALS;
HISTORY
AB While South Americans are underrepresented in human genomicdiversity studies, Brazil has been a classical model for population genetics studies on admixture. We present the results of the EPIGEN Brazil Initiative, the most comprehensive up-to-date genomic analysis of any Latin-American population. A population-based genome-wide analysis of 6,487 individuals was performed in the context of worldwide genomic diversity to elucidate how ancestry, kinship, and inbreeding interact in three populations with different histories from the Northeast (African ancestry: 50%), Southeast, and South (both with European ancestry >70%) of Brazil. We showed that ancestry-positive assortative mating permeated Brazilian history. We traced European ancestry in the Southeast/South to a wider European/Middle Eastern region with respect to the Northeast, where ancestry seems restricted to Iberia. By developing an approximate Bayesian computation framework, we infer more recent European immigration to the Southeast/South than to the Northeast. Also, the observed low Native-American ancestry (6-8%) was mostly introduced in different regions of Brazil soon after the European Conquest. We broadened our understanding of the African diaspora, the major destination of which was Brazil, by revealing that Brazilians display two within-Africa ancestry components: one associated with non-Bantu/western Africans (more evident in the Northeast and African Americans) and one associated with Bantu/eastern Africans (more present in the Southeast/South). Furthermore, the whole-genome analysis of 30 individuals (42-fold deep coverage) shows that continental admixture rather than local post-Columbian history is the main and complex determinant of the individual amount of deleterious genotypes.
C1 [Kehdy, Fernanda S. G.; Gouveia, Mateus H.; Machado, Moara; Magalhaes, Wagner C. S.; Moreira, Rennan G.; Leal, Thiago P.; Scliar, Marilia O.; Soares-Souza, Giordano B.; Rodrigues-Soares, Fernanda; Araujo, Gilderlanio S.; Zamudio, Roxana; Anna, Hanaisa P. Sant; Rodrigues, Maira R.; Tarazona-Santos, Eduardo] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Biol Geral, BR-31270901 Belo Horizonte, MG, Brazil.
[Horimoto, Andrea R.; Santos, Hadassa C.; Duarte, Nubia E.; Pereira, Alexandre C.] Univ Sao Paulo, Inst Coracao, BR-05403900 Sao Paulo, SP, Brazil.
[Horta, Bernardo L.] Univ Fed Pelotas, Programa Posgrad Epidemiol, BR-96001970 Pelotas, RS, Brazil.
[Fiaccone, Rosemeire L.] Univ Fed Bahia, Inst Matemat, Dept Estatist, BR-40170110 Salvador, Bahia, Brazil.
[Figueiredo, Camila A.] Univ Fed Bahia, Inst Ciencias Saude, Dept Ciencias Biointeracao, BR-40110100 Salvador, Bahia, Brazil.
[Silva, Thiago M.; Costa, Gustavo N. O.; Barreto, Mauricio L.] Univ Fed Bahia, Inst Saude Colet, BR-40110040 Salvador, Bahia, Brazil.
[Beleza, Sandra] Univ Leicester, Dept Genet, Leicester LE1 7RH, Leics, England.
[Berg, Douglas E.] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA.
[Berg, Douglas E.] Univ Calif San Diego, Dept Med, San Diego, CA 92093 USA.
[Cabrera, Lilia] AB PRISMA, Biomed Res Unit, Lima 170070, Peru.
[Debortoli, Guilherme; Marrero, Andrea R.; Muniz, Yara C.] Univ Fed Santa Catarina, Dept Biol Celular Embriol & Genet, BR-88040900 Florianopolis, SC, Brazil.
[Duarte, Denise] Univ Fed Minas Gerais, Dept Estatist, BR-31270901 Belo Horizonte, MG, Brazil.
[Ghirotto, Silvia] Univ Ferrara, Dipartimento Sci Vita & Biotecnol, I-44121 Ferrara, Italy.
[Gilman, Robert H.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Int Hlth, Baltimore, MD 21205 USA.
[Gilman, Robert H.] Univ Peruana Cayetano Heredia, Lab Invest Enfermedades Infecciosas, Lima 15102, Peru.
[Goncalves, Vanessa F.] Univ Toronto, Ctr Addict & Mental Hlth, Dept Psychiat, Toronto, ON M5T 1R8, Canada.
[Goncalves, Vanessa F.] Univ Toronto, Ctr Addict & Mental Hlth, Neurosci Sect, Toronto, ON M5T 1R8, Canada.
[Weissensteiner, Hansi] Med Univ Innsbruck, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, A-6020 Innsbruck, Austria.
[Yeager, Meredith] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Canc Genom Res Lab, Frederick, MD 20850 USA.
[Rodrigues, Laura C.] London Sch Hyg & Trop Med, Fac Epidemiol, Dept Infect Dis Epidemiol, London WC1E 7HT, England.
[Lima-Costa, M. Fernanda] Fundacao Oswaldo Cruz, Inst Pesquisa Rene Rachou, BR-30190002 Belo Horizonte, MG, Brazil.
RP Tarazona-Santos, E (reprint author), Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Biol Geral, BR-31270901 Belo Horizonte, MG, Brazil.
EM edutars@icb.ufmg.br
RI Horta, Bernardo/A-7604-2008; Rodrigues Soares, Fernanda/E-7122-2016;
Figueiredo, Camila/H-3525-2015; Magalhaes, Wagner/D-8822-2015;
Debortoli, Guilherme/I-7866-2016;
OI Figueiredo, Camila/0000-0003-1356-6188; Debortoli,
Guilherme/0000-0003-4320-5850; Barreto, Mauricio/0000-0002-0215-4930;
Nunes de Oliveira Costa, Gustavo/0000-0003-3445-0192
FU Brazilian Ministry of Health (Department of Science and Technology from
the Secretaria de Ciencia, Tecnologia e Insumos Estrategicos) through
Financiadora de Estudos e Projetos; Brazilian Ministry of Education
(CAPES Agency); Brazilian National Research Council (CNPq); Pro-Reitoria
de Pesquisa from the Universidade Federal de Minas Gerais; Minas Gerais
State Agency for Support of Research (FAPEMIG)
FX The authors thank David Alexander and Fernando Levi Soares for technical
help and discussion and Rasmus Nielsen and Mason Liang for sharing their
software for continuous specific ancestry simulations and feedback on
its use. Centro Nacional de Processamento de Alto Desempenho em
MG/Financiadora de Estudos e Projetos-Ministerio da Ciencia, Tecnologia
e Inovacao, Centro Nacional de Super Computacao, and Programa de
Desenvolvimento Tecnologico em Insumos para Saude-Bioinformatics
Platform at Fundacao Oswaldo Cruz-Minas Gerais provided computational
support. The EPIGEN Brazil Initiative is funded by the Brazilian
Ministry of Health (Department of Science and Technology from the
Secretaria de Ciencia, Tecnologia e Insumos Estrategicos) through
Financiadora de Estudos e Projetos. The EPIGEN Brazil investigators
received funding from the Brazilian Ministry of Education (CAPES
Agency), Brazilian National Research Council (CNPq), Pro-Reitoria de
Pesquisa from the Universidade Federal de Minas Gerais, and the Minas
Gerais State Agency for Support of Research (FAPEMIG).
NR 42
TC 19
Z9 19
U1 7
U2 17
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 14
PY 2015
VL 112
IS 28
BP 8696
EP 8701
DI 10.1073/pnas.1504447112
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CM7MU
UT WOS:000357878700056
PM 26124090
ER
PT J
AU Moshkovits, I
Karo-Atar, D
Itan, M
Reichman, H
Rozenberg, P
Morgenstern-Ben-Baruch, N
Shik, D
Ejarque-Ortiz, A
Hershko, AY
Tian, LJ
Coligan, JE
Sayos, J
Munitz, A
AF Moshkovits, Itay
Karo-Atar, Danielle
Itan, Michal
Reichman, Hadar
Rozenberg, Perri
Morgenstern-Ben-Baruch, Netali
Shik, Dana
Ejarque-Ortiz, Aroa
Hershko, Alon Y.
Tian, Linjie
Coligan, John E.
Sayos, Joan
Munitz, Ariel
TI CD300f associates with IL-4 receptor alpha and amplifies IL-4-induced
immune cell responses
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE IL-4 receptor; eosinophil; macrophage; CD300f; inflammation
ID IMMUNOGLOBULIN-LIKE RECEPTOR; IN-VIVO; PHOSPHATIDYLSERINE; ACTIVATION;
FAMILY; POLARIZATION; INFLAMMATION; MACROPHAGES; EXPRESSION; REGULATORS
AB IL-4 receptor (R) alpha, the common receptor chain for IL-4 and IL-13, is a critical component in IL-4- and IL-13-mediated signaling and subsequent effector functions such as those observed in type 2 inflammatory responses. Nonetheless, the existence of intrinsic pathways capable of amplifying IL-4R alpha-induced responses remains unknown. In this study, we identified the myeloid-associated Ig receptor CD300f as an IL-4-induced molecule in macrophages. Subsequent analyses demonstrated that CD300f was colocalized and physically associated with IL-4R alpha. Using Cd300f(-/-) cells and receptor cross-linking experiments, we established that CD300f amplified IL-4R alpha-induced responses by augmenting IL-4/IL-13-induced signaling, mediator release, and priming. Consistently, IL-4- and aeroallergen-treated Cd300f(-/-) mice displayed decreased IgE production, chemokine expression, and inflammatory cell recruitment. Impaired responses in Cd300f(-/-) mice were not due to the inability to generate a proper Th2 response, because IL-4/IL-13 levels were markedly increased in allergen-challenged Cd300f(-/-) mice, a finding that is consistent with decreased cytokine consumption. Finally, CD300f expression was increased in monocytes and eosinophils obtained from allergic rhinitis patients. Collectively, our data highlight a previously unidentified role for CD300f in IL-4R alpha-induced immune cell responses. These data provide new insights into the molecular mechanisms governing IL-4R alpha-induced responses, and may provide new therapeutic tools to target IL-4 in allergy and asthma.
C1 [Moshkovits, Itay; Karo-Atar, Danielle; Itan, Michal; Reichman, Hadar; Rozenberg, Perri; Morgenstern-Ben-Baruch, Netali; Shik, Dana; Munitz, Ariel] Tel Aviv Univ, Sackler Sch Med, Dept Clin Microbiol & Immunol, IL-69978 Ramat Aviv, Israel.
[Ejarque-Ortiz, Aroa; Sayos, Joan] Univ Autonoma Barcelona, Hosp Univ Vall DHebron, Ctr Invest Bioquim & Biol Mol, Inst Recerca,Immunobiol Grp,Nanomed Nanomed Progr, Barcelona 08035, Spain.
[Hershko, Alon Y.] Meir Med Ctr, Herbert Ctr Mast Cell Disorders, Dept Med, Lab Allergy & Clin Immunol, IL-44261 Kefar Sava, Israel.
[Tian, Linjie; Coligan, John E.] NIAID, Receptor Cell Biol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
RP Munitz, A (reprint author), Tel Aviv Univ, Sackler Sch Med, Dept Clin Microbiol & Immunol, IL-69978 Ramat Aviv, Israel.
EM arielm@post.tau.ac.il
FU Morasha Program [1084/10]; US-Israel Binational Science Foundation
[2011244]; Israel Science Foundation [955/11]; Varda and Boaz Dotan
Research Grant in Hemato-oncology; Israel Cancer Research Association;
Fondo de Investigaciones Sanitarias [PI1100045]; National Institute of
Allergy and Infectious Diseases Intramural Research Program
FX We thank Dr. Menno van Lookeren Campange (Genentech) for providing
critical reagents for this study. I.M. performed this work in
fulfillment of the requirements for a PhD degree at The Sackler School
of Medicine, Tel Aviv University. A.Y.H. is supported by the Morasha
Program (Grant 1084/10). A.M. is supported by the US-Israel Binational
Science Foundation (Grant 2011244), Israel Science Foundation (Grant
955/11), the Varda and Boaz Dotan Research Grant in Hemato-oncology, and
Israel Cancer Research Association. J.S. is supported by Fondo de
Investigaciones Sanitarias (Grant PI1100045). J.E.C. is supported by the
National Institute of Allergy and Infectious Diseases Intramural
Research Program.
NR 31
TC 6
Z9 7
U1 0
U2 6
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 14
PY 2015
VL 112
IS 28
BP 8708
EP 8713
DI 10.1073/pnas.1507625112
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CM7MU
UT WOS:000357878700058
PM 26124135
ER
PT J
AU Gonzalez-Castillo, J
Hoy, CW
Handwerker, DA
Robinson, ME
Buchanan, LC
Saad, ZS
Bandettini, PA
AF Gonzalez-Castillo, Javier
Hoy, Colin W.
Handwerker, Daniel A.
Robinson, Meghan E.
Buchanan, Laura C.
Saad, Ziad S.
Bandettini, Peter A.
TI Tracking ongoing cognition in individuals using brief, whole-brain
functional connectivity patterns
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE fMRI; connectivity dynamics; functional connectivity states; cognitive
states; classification
ID RESTING-STATE NETWORKS; FMRI CONNECTIVITY; DYNAMICS; SCALE;
CONSCIOUSNESS; ACTIVATION; HUMANS; TASKS
AB Functional connectivity (FC) patterns in functional MRI exhibit dynamic behavior on the scale of seconds, with rich spatiotemporal structure and limited sets of whole-brain, quasi-stable FC configurations (FC states) recurring across time and subjects. Based on previous evidence linking various aspects of cognition to group-level, minute-to-minute FC changes in localized connections, we hypothesized that whole-brain FC states may reflect the global, orchestrated dynamics of cognitive processing on the scale of seconds. To test this hypothesis, subjects were continuously scanned as they engaged in and transitioned between mental states dictated by tasks. FC states computed within windows as short as 22.5 s permitted robust tracking of cognition in single subjects with near perfect accuracy. Accuracy dropped markedly for subjects with the lowest task performance. Spatially restricting FC information decreased accuracy at short time scales, emphasizing the distributed nature of whole-brain FC dynamics, beyond univariate magnitude changes, as valuable markers of cognition.
C1 [Gonzalez-Castillo, Javier; Hoy, Colin W.; Handwerker, Daniel A.; Robinson, Meghan E.; Buchanan, Laura C.; Bandettini, Peter A.] NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
[Hoy, Colin W.] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA.
[Robinson, Meghan E.] Vet Affairs Boston Healthcare Syst, Boston, MA 02130 USA.
[Saad, Ziad S.] NIMH, Stat & Sci Comp Core, NIH, Bethesda, MD 20892 USA.
[Bandettini, Peter A.] NIMH, Funct MRI Facil, NIH, Bethesda, MD 20892 USA.
RP Gonzalez-Castillo, J (reprint author), NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
EM javier.gonzalez-castillo@nih.gov
OI Gonzalez-Castillo, Javier/0000-0002-6520-5125
FU National Institute of Mental Health Intramural Research Program
FX This research was possible thanks to the support of the National
Institute of Mental Health Intramural Research Program. Portions of this
study used the high-performance computational capabilities of the
Biowulf Linux cluster at the National Institutes of Health, Bethesda, MD
(biowulf.nih.gov). This study is part of NIH clinical protocol number
NCT00001360 and protocol ID 93-M-0170.
NR 49
TC 22
Z9 22
U1 2
U2 8
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 14
PY 2015
VL 112
IS 28
BP 8762
EP 8767
DI 10.1073/pnas.1501242112
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CM7MU
UT WOS:000357878700067
PM 26124112
ER
PT J
AU Liu, F
Koepp, DM
Walters, KJ
AF Liu, Fen
Koepp, Deanna M.
Walters, Kylie J.
TI Artificial targeting of misfolded cytosolic proteins to endoplasmic
reticulum as a mechanism for clearance
SO SCIENTIFIC REPORTS
LA English
DT Article
ID UBIQUITIN-LIKE DOMAIN; QUALITY-CONTROL; COTRANSLATIONAL UBIQUITINATION;
BLADDER-CANCER; DEGRADATION; RIBOSOME; ACETYLATION; PHENOTYPE;
MITOPHAGY; CHAPERONE
AB We report that misfolded cytosolic proteins can be cleared from mammalian cells by directing them to endoplasmic reticulum (ER). NAT1 R64W and Parkin R42P are naturally occurring misfolded variants of cytosolic enzymes that acetylate arylamines and ubiquitinate proteins, respectively. We demonstrate that proteasome inhibition causes ER accumulation of NAT1 R64W and its ubiquitinated species, and that these products are cleared from cells following inhibition release. NAT1 WT by contrast is stable and not present at ER. The R42P mutation in Parkin locates to a UBL domain that interacts with C-terminal domains. Parkin R42P full length protein is trafficked poorly to ER and stable. Interestingly, fusion of the isolated R42P UBL to NAT1 WT results in a fusion product that is trafficked robustly to ER and degraded. Thus, the misfolded UBL is apparently masked by the intramolecular interactions. We also find that artificially directing Parkin R42P to ER by fusion with the Sec61 beta ER-directing transmembrane domain triggers its clearance. Altogether, our results suggest that routing misfolded cytosolic proteins to ER may be an effective strategy for clearance.
C1 [Liu, Fen; Walters, Kylie J.] NCI, Protein Proc Sect, Struct Biophys Lab, Ctr Canc Res, Frederick, MD 21702 USA.
[Koepp, Deanna M.] Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA.
RP Walters, KJ (reprint author), NCI, Protein Proc Sect, Struct Biophys Lab, Ctr Canc Res, Frederick, MD 21702 USA.
EM kylie.walters@nih.gov
FU NIH [CA117888, GM076663]; American Cancer Society [RSG-07-186-01-GMC];
Intramural Research Program of the NIH, NCI, CCR
FX We are indebted to Patrick Hanna (University of Minnesota) for useful
discussions, Gia Voeltz (University of Colorado) for mCherry-Sec61 beta,
BFP-Sec61 beta and mCherry-Rab7 plasmids, Poul H. Jensen (University of
Aarhus, Denmark) for SHSY5Y cells stably expressing Parkin WT or R42P,
Ted Dawson (The Johns Hopkins University School of Medicine) for
Myc-Parkin R42P plasmid, Jadranka Loncarek (NCI) for technical advice
and sharing her microscope, Vinay Pathak and R. Andy Byrd (NCI) for
sharing instruments, Stephen Lockett and Valentin Magidson at the
Optical Microscopy and Analysis Laboratory (NCI) for technical
assistance. This research was funded by grants from the NIH (CA117888 to
KJW, GM076663 to DMK), American Cancer Society (RSG-07-186-01-GMC to
KJW), and by the Intramural Research Program of the NIH, NCI, CCR.
NR 34
TC 0
Z9 0
U1 0
U2 1
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 JUL 14
PY 2015
VL 5
AR 12088
DI 10.1038/srep12088
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CM7HV
UT WOS:000357863200001
PM 26168740
ER
PT J
AU Hoinka, J
Berezhnoy, A
Dao, P
Sauna, ZE
Gilboa, E
Przytycka, TM
AF Hoinka, Jan
Berezhnoy, Alexey
Phuong Dao
Sauna, Zuben E.
Gilboa, Eli
Przytycka, Teresa M.
TI Large scale analysis of the mutational landscape in HT-SELEX improves
aptamer discovery
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID THROUGHPUT SEQUENCE-ANALYSIS; RNA APTAMERS; ESCHERICHIA-COLI; SELECTION;
LIGANDS; IDENTIFICATION; OPTIMIZATION; GENERATION; IL-10
AB High-Throughput (HT) SELEX combines SELEX (Systematic Evolution of Ligands by EXponential Enrichment), a method for aptamer discovery, with massively parallel sequencing technologies. This emerging technology provides data for a global analysis of the selection process and for simultaneous discovery of a large number of candidates but currently lacks dedicated computational approaches for their analysis. To close this gap, we developed novel in-silico methods to analyze HT-SELEX data and utilized them to study the emergence of polymerase errors during HT-SELEX. Rather than considering these errors as a nuisance, we demonstrated their utility for guiding aptamer discovery. Our approach builds on two main advancements in aptamer analysis: AptaMut--a novel technique allowing for the identification of polymerase errors conferring an improved binding affinity relative to the 'parent' sequence and AptaCluster--an aptamer clustering algorithm which is to our best knowledge, the only currently available tool capable of efficiently clustering entire aptamer pools. We applied these methods to an HT-SELEX experiment developing aptamers against Interleukin 10 receptor alpha chain (IL-10RA) and experimentally confirmed our predictions thus validating our computational methods.
C1 [Hoinka, Jan; Phuong Dao; Przytycka, Teresa M.] NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
[Berezhnoy, Alexey; Gilboa, Eli] Univ Miami, Miller Sch Med, Dept Microbiol & Immunol, Miami, FL 33101 USA.
[Sauna, Zuben E.] US FDA, Lab Hemostasis, Div Hematol, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA.
RP Przytycka, TM (reprint author), NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
EM przytyck@ncbi.nlm.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Library of Medicine; Laboratory of Hemostasis; Center for
Biologics Evaluation and Research, Food and Drug Administration's Chief
Scientist Challenge Grant; Dodson estate; Sylvester Comprehensive Cancer
Center, Medical School, University of Miami; National Institutes of
Health
FX Intramural Research Program of the National Institutes of Health,
National Library of Medicine [J.H., P.D., T.M.P., in part]; Laboratory
of Hemostasis and the Center for Biologics Evaluation and Research, Food
and Drug Administration's Chief Scientist Challenge Grant [Z.E.S., in
part]; Dodson estate and the Sylvester Comprehensive Cancer Center,
Medical School, University of Miami [A.B., E.G., in part]. 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. The findings and conclusions in this
article have not been formally disseminated by the Food and Drug
Administration and should not be construed to represent any Agency
determination or policy.
NR 41
TC 18
Z9 18
U1 5
U2 18
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JUL 13
PY 2015
VL 43
IS 12
BP 5699
EP 5707
DI 10.1093/nar/gkv308
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CP3JM
UT WOS:000359775200009
PM 25870409
ER
PT J
AU Sarkar, J
Wan, BB
Yin, JH
Vallabhaneni, H
Horvath, K
Kulikowicz, T
Bohr, VA
Zhang, YB
Lei, M
Liu, Y
AF Sarkar, Jaya
Wan, Bingbing
Yin, Jinhu
Vallabhaneni, Haritha
Horvath, Kent
Kulikowicz, Tomasz
Bohr, Vilhelm A.
Zhang, Yanbin
Lei, Ming
Liu, Yie
TI SLX4 contributes to telomere preservation and regulated processing of
telomeric joint molecule intermediates
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID ELONGATION HELICASE 1; MAMMALIAN TELOMERES; PROTEINS TRF1; DNA-REPAIR;
FRAGILE SITES; BLM HELICASE; HUMAN-CELLS; S-PHASE; RTEL1; RECOMBINATION
AB SLX4 assembles a toolkit of endonucleases SLX1, MUS81 and XPF, which is recruited to telomeres via direct interaction of SLX4 with TRF2. Telomeres present an inherent obstacle for DNA replication and repair due to their high propensity to form branched DNA intermediates. Here we provide novel insight into the mechanism and regulation of the SLX4 complex in telomere preservation. SLX4 associates with telomeres throughout the cell cycle, peaking in late S phase and under genotoxic stress. Disruption of SLX4's interaction with TRF2 or SLX1 and SLX1's nuclease activity independently causes telomere fragility, suggesting a requirement of the SLX4 complex for nucleolytic resolution of branched intermediates during telomere replication. Indeed, the SLX1-SLX4 complex processes a variety of telomeric joint molecules in vitro. The nucleolytic activity of SLX1-SLX4 is negatively regulated by telomeric DNA-binding proteins TRF1 and TRF2 and is suppressed by the RecQ helicase BLM in vitro. In vivo, in the presence of functional BLM, telomeric circle formation and telomere sister chromatid exchange, both arising out of nucleolytic processing of telomeric homologous recombination intermediates, are suppressed. We propose that the SLX4-toolkit is a telomere accessory complex that, in conjunction with other telomere maintenance proteins, ensures unhindered, but regulated telomere maintenance.
C1 [Sarkar, Jaya; Yin, Jinhu; Vallabhaneni, Haritha; Horvath, Kent; Kulikowicz, Tomasz; Bohr, Vilhelm A.; Lei, Ming; Liu, Yie] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
[Wan, Bingbing; Lei, Ming] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell, Natl Ctr Prot Sci Shanghai,State Key Lab Mol Biol, Shanghai 200031, Peoples R China.
[Wan, Bingbing] Univ Michigan, Sch Med, Dept Biol Chem, Ann Arbor, MI 48109 USA.
[Zhang, Yanbin] Univ Miami, Miller Sch Med, Dept Biochem & Mol Biol, Miami, FL 33136 USA.
RP Liu, Y (reprint author), NIA, Lab Mol Gerontol, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM leim@sibcb.ac.cn; liuyie@mail.nih.gov
RI Zhang, Yanbin/F-2998-2011
OI Zhang, Yanbin/0000-0002-7263-5510
FU Intramural Research Program of the National Institutes of Health,
National Institute on Aging; Ministry of Science and Technology of China
[2013CB910402]; National Natural Science Foundation of China [31330040];
Strategic Priority Research Program of the Chinese Academy of Sciences
[XDB08010201]
FX The Intramural Research Program of the National Institutes of Health,
National Institute on Aging; the Ministry of Science and Technology of
China [2013CB910402]; the National Natural Science Foundation of China
[31330040]; the Strategic Priority Research Program of the Chinese
Academy of Sciences [XDB08010201]. Funding for open access charge: the
Intramural Research Program of the National Institutes of Health,
National Institute on Aging.
NR 49
TC 9
Z9 9
U1 2
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JUL 13
PY 2015
VL 43
IS 12
BP 5912
EP 5923
DI 10.1093/nar/gkv522
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CP3JM
UT WOS:000359775200025
PM 25990736
ER
PT J
AU Levay, A
Brenneman, R
Hoinka, J
Sant, D
Cardone, M
Trinchieri, G
Przytycka, TM
Berezhnoy, A
AF Levay, Agata
Brenneman, Randall
Hoinka, Jan
Sant, David
Cardone, Marco
Trinchieri, Giorgio
Przytycka, Teresa M.
Berezhnoy, Alexey
TI Identifying high-affinity aptamer ligands with defined cross-reactivity
using high-throughput guided systematic evolution of ligands by
exponential enrichment
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID QUANTITATIVE SELECTION; SIRNA CHIMERAS; GENERATION; INHIBITION;
ANTIBODIES
AB Oligonucleotide aptamers represent a novel platform for creating ligands with desired specificity, and they offer many potentially significant advantages over monoclonal antibodies in terms of feasibility, cost, and clinical applicability. However, the isolation of high-affinity aptamer ligands from random oligonucleotide pools has been challenging. Although high-throughput sequencing (HTS) promises to significantly facilitate systematic evolution of ligands by exponential enrichment (SELEX) analysis, the enormous datasets generated in the process pose new challenges for identifying those rare, high-affinity aptamers present in a given pool. We show that emulsion PCR preserves library diversity, preventing the loss of rare high-affinity aptamers that are difficult to amplify. We also demonstrate the importance of using reference targets to eliminate binding candidates with reduced specificity. Using a combination of bioinformatics and functional analyses, we show that the rate of amplification is more predictive than prevalence with respect to binding affinity and that the mutational landscape within a cluster of related aptamers can guide the identification of highaffinity aptamer ligands. Finally, we demonstrate the power of this selection process for identifying crossspecies aptamers that can bind human receptors and cross-react with their murine orthologs.
C1 [Levay, Agata; Brenneman, Randall; Sant, David; Berezhnoy, Alexey] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA.
[Hoinka, Jan; Przytycka, Teresa M.] NIH, Natl Lib Med, NCBI, Bethesda, MD 20894 USA.
[Cardone, Marco; Trinchieri, Giorgio] NCI, Canc Inflammat Program, Ctr Canc Res, NIH, Frederick, MD 21701 USA.
[Berezhnoy, Alexey] Univ Miami, Miller Sch Med, Dept Med, Miami, FL 33136 USA.
RP Berezhnoy, A (reprint author), Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA.
EM ABerezhnoy@med.miami.edu
FU University of Miami Aptamer Development Initiative
FX Funding for open access charge: University of Miami Aptamer Development
Initiative.
NR 24
TC 13
Z9 14
U1 6
U2 25
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JUL 13
PY 2015
VL 43
IS 12
AR e82
DI 10.1093/nar/gkv534
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CP3JM
UT WOS:000359775200006
PM 26007661
ER
PT J
AU Baikara, BT
Zholdybayeva, EV
Rakhimova, SE
Nigmatullina, NB
Momynaliev, KT
Ramanculov, YM
AF Baikara, Barshagul T.
Zholdybayeva, Elena V.
Rakhimova, Saule E.
Nigmatullina, Nazym B.
Momynaliev, Kuvat T.
Ramanculov, Yerlan M.
TI A Novel Mutation in a Kazakh Family with X-Linked Alport Syndrome
SO PLOS ONE
LA English
DT Article
ID PHENOTYPE CORRELATIONS; IV COLLAGEN; GENE
AB Alport syndrome is a genetic condition that results in hematuria, progressive renal impairment, hearing loss, and occasionally lenticonus and retinopathy. Approximately 80% of Alport syndrome cases are caused by X-linked mutations in the COL4A5 gene encoding type IV collagen. The objective of this study was to define the SNP profiles for COL4A5 in patients with hereditary nephritis and hematuria. For this, we examined four subjects from one Kazakh family clinically affected with X-linked Alport syndrome due to COL4A5 gene mutations. All 51 exons of the COL4A5 gene were screened by linkage analysis and direct DNA sequencing, resulting in the identification of a novel mutation (G641E) in exon 25. The mutation was found only in two affected family individuals but was not present in healthy family members or 200 unrelated healthy controls. This result demonstrates that this novel mutation is pathogenic and has meaningful implications for the diagnosis of patients with Alport syndrome.
C1 [Baikara, Barshagul T.; Zholdybayeva, Elena V.; Rakhimova, Saule E.; Momynaliev, Kuvat T.; Ramanculov, Yerlan M.] Natl Biotechnol Ctr, Astana, Kazakhstan.
[Rakhimova, Saule E.] Nazarbayev Univ, Ctr Sci, Astana, Kazakhstan.
[Nigmatullina, Nazym B.] Natl Res Ctr Maternal & Child Hlth, Astana, Kazakhstan.
[Ramanculov, Yerlan M.] Nazarbayev Univ, Sch Sci & Technol, Astana, Kazakhstan.
RP Baikara, BT (reprint author), Natl Biotechnol Ctr, Astana, Kazakhstan.
EM baikara.barshagul@gmail.com
FU Ministry of Education and Science of the Republic of Kazakhstan;
National Center for Biotechnology
FX This study was supported by the Ministry of Education and Science of the
Republic of Kazakhstan. The National Center for Biotechnology received
this grant. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 17
TC 1
Z9 1
U1 2
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 JUL 13
PY 2015
VL 10
IS 7
AR e0132010
DI 10.1371/journal.pone.0132010
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN1PW
UT WOS:000358193100017
PM 26168235
ER
PT J
AU Rapoport, SI
Primiani, CT
Chen, CT
Ahn, K
Ryan, VH
AF Rapoport, Stanley I.
Primiani, Christopher T.
Chen, Chuck T.
Ahn, Kwangmi
Ryan, Veronica H.
TI Coordinated Expression of Phosphoinositide Metabolic Genes during
Development and Aging of Human Dorsolateral Prefrontal Cortex
SO PLOS ONE
LA English
DT Article
ID INOSITOL POLYPHOSPHATE MULTIKINASE; ALZHEIMERS-DISEASE; HUMAN BRAIN;
DOWNS-SYNDROME; TRISPHOSPHATE RECEPTOR; SIGNALING PATHWAY;
CEREBRAL-CORTEX; MESSENGER-RNA; H-1 MRS; PROTEIN
AB Background
Phosphoinositides, lipid-signaling molecules, participate in diverse brain processes within a wide metabolic cascade.
Hypothesis
Gene transcriptional networks coordinately regulate the phosphoinositide cascade during human brain Development and Aging.
Methods
We used the public BrainCloud database for human dorsolateral prefrontal cortex to examine age-related expression levels of 49 phosphoinositide metabolic genes during Development (0 to 20+ years) and Aging (21+ years).
Results
We identified three groups of partially overlapping genes in each of the two intervals, with similar intergroup correlations despite marked phenotypic differences between Aging and Development. In each interval, ITPKB, PLCD1, PIK3R3, ISYNA1, IMPA2, INPPL1, PI4KB, and AKT1 are in Group 1, PIK3CB, PTEN, PIK3CA, and IMPA1 in Group 2, and SACM1L, PI3KR4, INPP5A, SYNJ1, and PLCB1 in Group 3. Ten of the genes change expression non-linearly during Development, suggesting involvement in rapidly changing neuronal, glial and myelination events. Correlated transcription for some gene pairs likely is facilitated by colocalization on the same chromosome band.
Conclusions
Stable coordinated gene transcriptional networks regulate brain phosphoinositide metabolic pathways during human Development and Aging.
C1 [Rapoport, Stanley I.; Primiani, Christopher T.; Ryan, Veronica H.] NIA, Brain Physiol & Metab Sect, Neurosci Lab, NIH, Bethesda, MD 20892 USA.
[Chen, Chuck T.] NIAAA, Sect Nutr Neurosci, NIH, Bethesda, MD USA.
[Ahn, Kwangmi] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA.
RP Rapoport, SI (reprint author), NIA, Brain Physiol & Metab Sect, Neurosci Lab, NIH, Bethesda, MD 20892 USA.
EM sir@nih.gov
FU Intramural Research Programs of the National Institute on Aging,
National Institute on Alcohol Abuse and Alcoholism, National Institute
of Mental Health
FX The Intramural Research Programs of the National Institute on Aging,
National Institute on Alcohol Abuse and Alcoholism, National Institute
of Mental Health supported this research.
NR 74
TC 1
Z9 1
U1 2
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 JUL 13
PY 2015
VL 10
IS 7
AR e0132675
DI 10.1371/journal.pone.0132675
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN1PW
UT WOS:000358193100065
PM 26168237
ER
PT J
AU Ueo, H
Shinden, Y
Tobo, T
Gamachi, A
Udo, M
Komatsu, H
Nambara, S
Saito, T
Ueda, M
Hirata, H
Sakimura, S
Takano, Y
Uchi, R
Kurashige, J
Akiyoshi, S
Iguchi, T
Eguchi, H
Sugimachi, K
Kubota, Y
Kai, Y
Shibuta, K
Kijima, Y
Yoshinaka, H
Natsugoe, S
Mori, M
Maehara, Y
Sakabe, M
Kamiya, M
Kakareka, JW
Pohida, TJ
Choyke, PL
Kobayashi, H
Ueo, H
Urano, Y
Mimori, K
AF Ueo, Hiroki
Shinden, Yoshiaki
Tobo, Taro
Gamachi, Ayako
Udo, Mitsuaki
Komatsu, Hisateru
Nambara, Sho
Saito, Tomoko
Ueda, Masami
Hirata, Hidenari
Sakimura, Shotaro
Takano, Yuki
Uchi, Ryutaro
Kurashige, Junji
Akiyoshi, Sayuri
Iguchi, Tomohiro
Eguchi, Hidetoshi
Sugimachi, Keishi
Kubota, Yoko
Kai, Yuichiro
Shibuta, Kenji
Kijima, Yuko
Yoshinaka, Heiji
Natsugoe, Shoji
Mori, Masaki
Maehara, Yoshihiko
Sakabe, Masayo
Kamiya, Mako
Kakareka, John W.
Pohida, Thomas J.
Choyke, Peter L.
Kobayashi, Hisataka
Ueo, Hiroaki
Urano, Yasuteru
Mimori, Koshi
TI Rapid intraoperative visualization of breast lesions with gamma-glutamyl
hydroxymethyl rhodamine green
SO SCIENTIFIC REPORTS
LA English
DT Article
ID FROZEN-SECTION ANALYSIS; CONSERVING SURGERY; MARGINS
AB We previously developed gamma-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG) as a tool to detect viable cancer cells, based on the fact that the enzyme gamma-glutamyltranspeptidase (GGT) is overexpressed on membranes of various cancer cells, but is not expressed in normal tissue. Cleavage of the probe by GGT generates green fluorescence. Here, we examined the feasibility of clinical application of gGlu-HMRG during breast-conserving surgery. We found that fluorescence derived from cleavage of gGlu-HMRG allowed easy discrimination of breast tumors, even those smaller than 1 mm in size, from normal mammary gland tissues, with 92% sensitivity and 94% specificity, within only 5 min after application. We believe this rapid, low-cost method represents a breakthrough in intraoperative margin assessment during breast-conserving surgery.
C1 [Ueo, Hiroki; Shinden, Yoshiaki; Komatsu, Hisateru; Nambara, Sho; Saito, Tomoko; Ueda, Masami; Hirata, Hidenari; Sakimura, Shotaro; Takano, Yuki; Uchi, Ryutaro; Kurashige, Junji; Akiyoshi, Sayuri; Iguchi, Tomohiro; Eguchi, Hidetoshi; Sugimachi, Keishi; Mimori, Koshi] Kyushu Univ, Beppu Hosp, Dept Surg, Beppu, Oita 8740838, Japan.
[Tobo, Taro; Udo, Mitsuaki] Kyushu Univ, Beppu Hosp, Dept Pathol, Beppu, Oita 8740838, Japan.
[Gamachi, Ayako] Oita Univ, Dept Pathol, Yufu 8795593, Japan.
[Kai, Yuichiro; Shibuta, Kenji; Ueo, Hiroaki] Ueo Breast Surg Hosp, Oita 8700854, Japan.
[Shinden, Yoshiaki; Kijima, Yuko; Yoshinaka, Heiji; Natsugoe, Shoji] Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Digest Surg Breast & Thyroid Surg, Kagoshima 8908520, Japan.
[Mori, Masaki] Osaka Univ, Grad Sch Med, Dept Surg Gastroenterol, Suita, Osaka 5650871, Japan.
[Ueo, Hiroki; Maehara, Yoshihiko] Kyushu Univ, Grad Sch Med Sci, Dept Surg & Sci, Fukuoka 8128582, Japan.
[Sakabe, Masayo; Kamiya, Mako; Urano, Yasuteru] Univ Tokyo, Grad Sch Med, Tokyo 1130033, Japan.
[Kakareka, John W.; Pohida, Thomas J.] NIH, Signal Proc & Instrumentat Sect, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
[Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Urano, Yasuteru] Japan Sci & Technol Agcy, Basic Res Program, Tokyo 1020076, Japan.
[Urano, Yasuteru] Japan Sci & Technol Agcy, CREST, Tokyo 1020076, Japan.
RP Urano, Y (reprint author), Univ Tokyo, Grad Sch Med, Tokyo 1130033, Japan.
EM uranokun@m.u-tokyo.ac.jp; kmimori@beppu.kyushu-u.ac.jp
RI U-ID, Kyushu/C-5291-2016
FU [25430111]; [25461953]; [25861199]; [25861200]; [24592005];
[21229015]
FX This work was supported by the following grants and foundations:
Grants-in-Aid for Scientific Research, grant numbers 25430111, 25461953,
25861199, 25861200, 24592005, and 21229015. We would thank to Ms. M.
Kasagi, Ms. S. Kohno, Ms. K. Oda, Ms. M. Aoyagi and Ms. T. Kawano for
their assistance of molecular biological procedures.
NR 12
TC 11
Z9 12
U1 5
U2 20
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 JUL 13
PY 2015
VL 5
AR 12080
DI 10.1038/srep12080
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CM7CV
UT WOS:000357848900001
PM 26165706
ER
PT J
AU Logue, JS
Cartagena-Rivera, AX
Baird, MA
Davidson, MW
Chadwick, RS
Waterman, CM
AF Logue, Jeremy S.
Cartagena-Rivera, Alexander X.
Baird, Michelle A.
Davidson, Michael W.
Chadwick, Richard S.
Waterman, Clare M.
TI Erk regulation of actin capping and bundling by Eps8 promotes cortex
tension and leader bleb-based migration
SO ELIFE
LA English
DT Article
ID ACTIVATED PROTEIN-KINASE; CELL-MIGRATION; CANCER-THERAPY; MYOSIN-II;
ADHESION; MOTILITY; GROWTH; GENE; MORPHOGENESIS; LAMELLIPODIA
AB Within the confines of tissues, cancer cells can use blebs to migrate. Eps8 is an actin bundling and capping protein whose capping activity is inhibited by Erk, a key MAP kinase that is activated by oncogenic signaling. We tested the hypothesis that Eps8 acts as an Erk effector to modulate actin cortex mechanics and thereby mediate bleb-based migration of cancer cells. Cells confined in a non-adhesive environment migrate in the direction of a very large 'leader bleb.' Eps8 bundling activity promotes cortex tension and intracellular pressure to drive leader bleb formation. Eps8 capping and bundling activities act antagonistically to organize actin within leader blebs, and Erk mediates this effect. An Erk biosensor reveals concentrated kinase activity within leader blebs. Bleb contents are trapped by the narrow neck that separates the leader bleb from the cell body. Thus, Erk activity promotes actin bundling by Eps8 to enhance cortex tension and drive the bleb-based migration of cancer cells under non-adhesive confinement.
C1 [Logue, Jeremy S.; Baird, Michelle A.; Waterman, Clare M.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Logue, Jeremy S.; Cartagena-Rivera, Alexander X.; Chadwick, Richard S.] NIDCD, NIH, Bethesda, MD USA.
[Davidson, Michael W.] Florida State Univ, Natl High Magnet Field Lab, Tallahassee, FL 32306 USA.
[Davidson, Michael W.] Florida State Univ, Dept Biol Sci, B-157, Tallahassee, FL 32306 USA.
RP Chadwick, RS (reprint author), NIDCD, NIH, Bethesda, MD USA.
EM chadwick@nidcd.nih.gov; watermancm@nhlbi.nih.gov
RI Cartagena-Rivera, Alexander/I-6101-2016
OI Waterman, Clare/0000-0001-6142-6775; Cartagena-Rivera,
Alexander/0000-0001-6227-2499
FU National Heart, Lung, and Blood Institute (NHBLI); National Institute on
Deafness and Other Communication Disorders (NIDCD)
FX Funder Author; National Heart, Lung, and Blood Institute (NHBLI) Clare M
Waterman; National Institute on Deafness and Other Communication
Disorders (NIDCD) Richard S Chadwick; The funders had no role in study
design, data collection and interpretation, or the decision to submit
the work for publication.
NR 51
TC 8
Z9 8
U1 2
U2 3
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD JUL 11
PY 2015
VL 4
AR e08314
DI 10.7554/eLife.08314
PG 31
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA DJ0GZ
UT WOS:000373881800001
PM 26163656
ER
PT J
AU Babbitt, PC
Bagos, PG
Bairoch, A
Bateman, A
Chatonnet, A
Chen, MJ
Craik, DJ
Finn, RD
Gloriam, D
Haft, DH
Henrissat, B
Holliday, GL
Isberg, V
Kaas, Q
Landsman, D
Lenfant, N
Manning, G
Nagano, N
Srinivasan, N
O'Donovan, C
Pruitt, KD
Sowdhamini, R
Rawlings, ND
Saier, MH
Sharman, JL
Spedding, M
Tsirigos, KD
Vastermark, A
Vriend, G
AF Babbitt, Patricia C.
Bagos, Pantelis G.
Bairoch, Amos
Bateman, Alex
Chatonnet, Arnaud
Chen, Mark Jinan
Craik, David J.
Finn, Robert D.
Gloriam, David
Haft, Daniel H.
Henrissat, Bernard
Holliday, Gemma L.
Isberg, Vignir
Kaas, Quentin
Landsman, David
Lenfant, Nicolas
Manning, Gerard
Nagano, Nozomi
Srinivasan, Narayanaswamy
O'Donovan, Claire
Pruitt, Kim D.
Sowdhamini, Ramanathan
Rawlings, Neil D.
Saier, Milton H., Jr.
Sharman, Joanna L.
Spedding, Michael
Tsirigos, Konstantinos D.
Vastermark, Ake
Vriend, Gerrit
TI Creating a specialist protein resource network: a meeting report for the
protein bioinformatics and community resources retreat
SO DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION
LA English
DT Article
ID DATABASE
AB During 11-12 August 2014, a Protein Bioinformatics and Community Resources Retreat was held at the Wellcome Trust Genome Campus in Hinxton, UK. This meeting brought together the principal investigators of several specialized protein resources (such as CAZy, TCDB and MEROPS) as well as those from protein databases from the large Bioinformatics centres (including UniProt and RefSeq). The retreat was divided into five sessions: (1) key challenges, (2) the databases represented, (3) best practices for maintenance and curation, (4) information flow to and from large data centers and (5) communication and funding. An important outcome of this meeting was the creation of a Specialist Protein Resource Network that we believe will improve coordination of the activities of its member resources. We invite further protein database resources to join the network and continue the dialogue.
C1 [Babbitt, Patricia C.; Holliday, Gemma L.] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94158 USA.
[Babbitt, Patricia C.; Holliday, Gemma L.] Univ Calif San Francisco, Calif Inst Quantitat Biosci, San Francisco, CA 94158 USA.
[Bagos, Pantelis G.] Univ Thessaly, Dept Comp Sci & Biomed Informat, Lamia 35100, Greece.
[Bairoch, Amos] CMU, SIB, CH-1211 Geneva 4, Switzerland.
[Bateman, Alex; Finn, Robert D.; O'Donovan, Claire; Rawlings, Neil D.] EBI, EMBL, Cambridge CB10 1SD, England.
[Chatonnet, Arnaud; Lenfant, Nicolas] INRA, UMR Dynam Musculaire & Metab 866, F-34000 Montpellier, France.
[Chen, Mark Jinan; Manning, Gerard] Salk Inst Biol Studies, Razavi Newman Ctr Bioinformat, La Jolla, CA 92037 USA.
[Chen, Mark Jinan; Manning, Gerard] Genentech Inc, Bioinformat & Computat Biol, San Francisco, CA 94080 USA.
[Craik, David J.; Kaas, Quentin] Univ Queensland, Queensland Biosci Precinct, Brisbane, Qld 4072, Australia.
[Gloriam, David; Isberg, Vignir] Univ Copenhagen, Dept Drug Design & Pharmacol, DK-2100 Copenhagen O, Denmark.
[Haft, Daniel H.; Landsman, David; Pruitt, Kim D.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
[Henrissat, Bernard] Aix Marseille Univ, CNRS, Architecture & Fonct Macromol Biol, F-13288 Marseille, France.
[Henrissat, Bernard] King Abdulaziz Univ, Dept Biol Sci, Jeddah 21413, Saudi Arabia.
[Isberg, Vignir; Vriend, Gerrit] Raboudumc, CMBI, NL-6525 GA Nijmegen, Netherlands.
[Nagano, Nozomi] Natl Inst Adv Ind Sci & Technol, Biotechnol Res Inst Drug Discovery, Koto Ku, Tokyo 1350064, Japan.
[Srinivasan, Narayanaswamy] Indian Inst Sci, Mol Biophys Unit, Bangalore 560012, Karnataka, India.
[Sowdhamini, Ramanathan] TIFR, Natl Ctr Biol Sci, Bangalore 560065, Karnataka, India.
[Saier, Milton H., Jr.; Vastermark, Ake] Univ Calif San Diego, Dept Mol Biol, La Jolla, CA 92093 USA.
[Sharman, Joanna L.] Univ Edinburgh, Ctr Integrat Physiol, Edinburgh EH8 9XD, Midlothian, Scotland.
[Spedding, Michael] Spedding Res Solut, F-78110 Le Vesinet, France.
[Tsirigos, Konstantinos D.] Stockholm Univ, Swedish E Sci Res Ctr, Dept Biochem & Biophys, Sci Life Lab, S-17121 Solna, Sweden.
RP Saier, MH (reprint author), Univ Calif San Diego, Dept Mol Biol, La Jolla, CA 92093 USA.
EM msaier@ucsd.edu
RI Chen, Jinan/O-3937-2014; Craik, David/B-1695-2010; Nagano,
Nozomi/A-5717-2017; Chatonnet, Arnaud/E-2190-2017; Fac Sci, KAU, Biol
Sci Dept/L-4228-2013; Rawlings, Neil/M-5566-2013; Isberg,
Vignir/A-2882-2011;
OI Holliday, Gemma/0000-0002-6731-6398; Kaas, Quentin/0000-0001-9988-6152;
O'Donovan, Claire/0000-0001-8051-7429; Gloriam,
David/0000-0002-4299-7561; Chen, Jinan/0000-0003-1169-563X; Craik,
David/0000-0003-0007-6796; Nagano, Nozomi/0000-0002-2779-685X;
Chatonnet, Arnaud/0000-0002-4057-3896; Tsirigos,
Konstantinos/0000-0001-5280-1107; Spedding, Michael/0000-0002-1248-8221;
Rawlings, Neil/0000-0001-5557-7665; Isberg, Vignir/0000-0002-1042-040X;
Manning, Gerard/0000-0002-5087-9151; Bairoch, Amos/0000-0003-2826-6444;
Landsman, David/0000-0002-9819-6675; Sharman, Joanna/0000-0002-5275-6446
FU NCBI/NLM/NIH/DHHS
FX Funding for open access charge: K.D.P, NCBI/NLM/NIH/DHHS.
NR 9
TC 5
Z9 5
U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1758-0463
J9 DATABASE-OXFORD
JI Database
PD JUL 11
PY 2015
AR bav063
DI 10.1093/database/bav063
PG 5
WC Mathematical & Computational Biology
SC Mathematical & Computational Biology
GA CR1AB
UT WOS:000361053900001
ER
PT J
AU Castillo, JC
Creasy, T
Kumari, P
Shetty, A
Shokal, U
Tallon, LJ
Eleftherianos, I
AF Castillo, Julio C.
Creasy, Todd
Kumari, Priti
Shetty, Amol
Shokal, Upasana
Tallon, Luke J.
Eleftherianos, Ioannis
TI Drosophila anti-nematode and antibacterial immune regulators revealed by
RNA-Seq
SO BMC GENOMICS
LA English
DT Article
DE Drosophila; Photorhabdus; Heterorhabditis; RNA-sequencing;
Transcriptomics; Immunity; Infection; Parasitism
ID IONOTROPIC GLUTAMATE RECEPTORS; THIOESTER-CONTAINING PROTEINS; LARGE
GENE LISTS; ENTOMOPATHOGENIC NEMATODES; PHOTORHABDUS-LUMINESCENS;
CUTICULAR PROTEINS; ANOPHELES-GAMBIAE; HOST-DEFENSE; ADULT FLIES;
MELANOGASTER
AB Background: Drosophila melanogaster activates a variety of immune responses against microbial infections. However, information on the Drosophila immune response to entomopathogenic nematode infections is currently limited. The nematode Heterorhabditis bacteriophora is an insect parasite that forms a mutualistic relationship with the gram-negative bacteria Photorhabdus luminescens. Following infection, the nematodes release the bacteria that quickly multiply within the insect and produce several toxins that eventually kill the host. Although we currently know that the insect immune system interacts with Photorhabdus, information on interaction with the nematode vector is scarce.
Results: Here we have used next generation RNA-sequencing to analyze the transcriptional profile of wild-type adult flies infected by axenic Heterorhabditis nematodes (lacking Photorhabdus bacteria), symbiotic Heterorhabditis nematodes (carrying Photorhabdus bacteria), and Photorhabdus bacteria alone. We have obtained approximately 54 million reads from the different infection treatments. Bioinformatic analysis shows that infection with Photorhabdus alters the transcription of a large number of Drosophila genes involved in translational repression as well in response to stress. However, Heterorhabditis infection alters the transcription of several genes that participate in lipidhomeostasis and metabolism, stress responses, DNA/protein sythesis and neuronal functions. We have also identified genes in the fly with potential roles in nematode recognition, anti-nematode activity and nociception.
Conclusions: These findings provide fundamental information on the molecular events that take place in Drosophila upon infection with the two pathogens, either separately or together. Such large-scale transcriptomic analyses set the stage for future functional studies aimed at identifying the exact role of key factors in the Drosophila immune response against nematode-bacteria complexes.
C1 [Castillo, Julio C.; Shokal, Upasana; Eleftherianos, Ioannis] George Washington Univ, Dept Biol Sci, Inst Biomed Sci, Insect Infect & Immun Lab, Washington, DC 20052 USA.
[Castillo, Julio C.] NIH, Lab Malaria & Vector Res, Rockville, MD 20852 USA.
[Creasy, Todd; Kumari, Priti; Shetty, Amol; Tallon, Luke J.] Univ Maryland, Sch Med, Inst Genome Sci, Dept Microbiol & Immunol, Baltimore, MD 21201 USA.
RP Eleftherianos, I (reprint author), George Washington Univ, Dept Biol Sci, Inst Biomed Sci, Insect Infect & Immun Lab, Washington, DC 20052 USA.
EM ioannise@gwu.edu
OI Castillo, Julio/0000-0002-6921-810X; Shokal, Upasana/0000-0003-3850-4661
FU Department of Biological Sciences at George Washington University (GWU);
University Facilitating Fund from the Columbian Collge of Arts and
Sciences at GWU
FX This work was supported by a start-up grant from the Department of
Biological Sciences at George Washington University (GWU) and a
University Facilitating Fund from the Columbian Collge of Arts and
Sciences at GWU.
NR 101
TC 6
Z9 6
U1 1
U2 19
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 JUL 11
PY 2015
VL 16
AR 519
DI 10.1186/s12864-015-1690-2
PG 21
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA CM6BX
UT WOS:000357773800001
PM 26162375
ER
PT J
AU Schnabel, RB
Yin, XY
Gona, P
Larson, MG
Beiser, AS
McManus, DD
Newton-Cheh, C
Lubitz, SA
Magnani, JW
Ellinor, PT
Seshadri, S
Wolf, PA
Vasan, RS
Benjamin, EJ
Levy, D
AF Schnabel, Renate B.
Yin, Xiaoyan
Gona, Philimon
Larson, Martin G.
Beiser, Alexa S.
McManus, David D.
Newton-Cheh, Christopher
Lubitz, Steven A.
Magnani, Jared W.
Ellinor, Patrick T.
Seshadri, Sudha
Wolf, Philip A.
Vasan, Ramachandran S.
Benjamin, Emelia J.
Levy, Daniel
TI 50 year trends in atrial fibrillation prevalence, incidence, risk
factors, and mortality in the Framingham Heart Study: a cohort study
SO LANCET
LA English
DT Article
ID LEFT-VENTRICULAR HYPERTROPHY; MEDICARE BENEFICIARIES; UNITED-STATES; US;
HYPERTENSION; ANTICOAGULATION; PROJECTIONS; POPULATION; SURVIVAL;
FAILURE
AB Background Comprehensive long-term data on atrial fibrillation trends in men and women are scant. We aimed to provide such data through analysis of the Framingham cohort over 50 years.
Methods We investigated trends in incidence, prevalence, and risk factors for atrial fibrillation and its association with stroke and mortality after onset in 9511 participants enrolled in the Framingham Heart Study between 1958 and 2007. We analysed trends within 10 year groups (1958-67, 1968-77, 1978-87, 1988-97, and 1998-2007), stratified by sex.
Findings During 50 years of observation (202 417 person-years), 1544 cases of new-onset atrial fibrillation occurred (of whom 723 [47%] were women). Between 1958-67 and 1998-2007, age-adjusted prevalence of atrial fibrillation quadrupled from 20.4 to 96.2 cases per 1000 person-years in men and from 13.7 to 49.4 cases per 1000 person-years in women; age-adjusted incidence increased from 3.7 to 13.4 new cases per 1000 person-years in men and from 2.5 to 8.6 new cases per 1000 person-years in women (p(trend) < 0.0001 for all comparisons). For atrial fibrillation diagnosed by electrocardiograph (ECG) during routine Framingham examinations, age-adjusted prevalence per 1000 person-years increased (12.6 in 1958-67 to 25.7 in 1998-2007 in men, p(trend) = 0.0007; 8.1 to 11.8 in women, p(trend) = 0.009). However, age-adjusted incidence of atrial fibrillation by Framingham Heart Study ECGs did not change significantly with time. Although the prevalence of most risk factors changed over time, their associated hazards for atrial fibrillation changed little. Multivariable-adjusted proportional hazards models revealed a 74% (95% CI 50-86%) decrease in stroke (hazards ratio [HR] 3.77, 95% CI 1.98-7.20 in 1958-1967 compared with 1998-2007; p(trend) = 0.0001) and a 25% (95% CI -3-46%) decrease in mortality (HR 1.34, 95% CI 0.97-1.86 in 1958-1967 compared with 1998-2007; p(trend) = 0.003) in 20 years following atrial fibrillation onset.
Interpretation Trends of increased incidence and prevalence of atrial fibrillation in the community were probably partly due to enhanced surveillance. Measures are needed to enhance early detection of atrial fibrillation, through increased awareness coupled with targeted screening programmes and risk factor-specific prevention.
C1 [Schnabel, Renate B.; Yin, Xiaoyan; Gona, Philimon; Larson, Martin G.; Beiser, Alexa S.; Newton-Cheh, Christopher; Seshadri, Sudha; Wolf, Philip A.; Vasan, Ramachandran S.; Benjamin, Emelia J.; Levy, Daniel] Natl Heart Lung & Blood Inst Framingham Study, Framingham, MA USA.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Larson, Martin G.; Beiser, Alexa S.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Evans Mem Med Dept, Boston, MA 02118 USA.
[Magnani, Jared W.; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA.
[Beiser, Alexa S.; Seshadri, Sudha; Wolf, Philip A.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Wolf, Philip A.; Vasan, Ramachandran S.; Benjamin, Emelia J.; Levy, Daniel] Boston Univ, Sch Med, Prevent Med Sect, Boston, MA 02118 USA.
[McManus, David D.] Univ Massachusetts, Sch Med, Dept Med, Div Cardiol, Boston, MA 02125 USA.
[Gona, Philimon] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Div Biostat & Hlth Serv Res, Boston, MA 02125 USA.
[Levy, Daniel] NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Newton-Cheh, Christopher; Ellinor, Patrick T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA USA.
[Newton-Cheh, Christopher] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA.
[Newton-Cheh, Christopher; Lubitz, Steven A.; Ellinor, Patrick T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA.
[Newton-Cheh, Christopher; Ellinor, Patrick T.] Broad Inst Harvard & MIT, Program Med Populat Genet, Cambridge, MA USA.
[Schnabel, Renate B.] Deutsch Zentrum Herz Kreislauf Forsch, Univ Heart Ctr, Dept Gen & Intervent Cardiol, Hamburg, Germany.
RP Schnabel, RB (reprint author), Univ Heart Ctr Hamburg Eppendorf, Dept Gen & Intervent Cardiol, D-20246 Hamburg, Germany.
EM r.schnabel@uke.de
OI Seshadri, Sudha/0000-0001-6135-2622; Ramachandran,
Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336; Beiser,
Alexa/0000-0001-8551-7778
FU NIH; NHLBI; NINDS; Deutsche Forschungsgemeinschaft; NIH/NHLBI
[N01-HC-25195, 1K23HL114724]; NIH [1RC1HL101056, HL102214, AG028321,
2R01HL092577, 1R01HL092577, 1R01HL102214, 1R01AG028321, R01HL104156,
1K24HL105780, HL080124, HL077477, HL71039, HL093328, 6RO1-NS-17950,
HL080025, 1U01HL105268-01, KL2RR031981]; Fondation Leducq [14CVD01];
American Heart Association [13EIA14220013]; Deutsche
Forschungsgemeinschaft (German Research Foundation) [SCHN 1149/3-2];
Doris Duke Charitable Foundation; Burroughs Wellcome Fund Career Award
for Medical Scientists
FX NIH, NHLBI, NINDS, Deutsche Forschungsgemeinschaft.; EJB was supported
by NIH/NHLBI contract N01-HC-25195 and NIH grants 1RC1HL101056,
HL102214, and AG028321. EJB and PTE were supported by NIH grant
2R01HL092577. PTE was supported by Fondation Leducq (14CVD01) and NIH
grants 1R01HL092577, 1RC1HL101056, 1R01HL102214, 1R01AG028321,
R01HL104156, and 1K24HL105780 and received the American Heart
Association Established Investigator Award 13EIA14220013. RSV was
supported by NIH grants HL080124, HL077477, HL71039, and HL093328. PAW,
SS, and ASB were supported by NIH grant 6RO1-NS-17950. RBS was supported
by the Deutsche Forschungsgemeinschaft (German Research Foundation) Emmy
Noether Program SCHN 1149/3-2. CNC was supported by the NIH grant
HL080025 and received the Doris Duke Charitable Foundation Clinical
Scientist Development Award and the Burroughs Wellcome Fund Career Award
for Medical Scientists. SAL was supported by the NIH/NHLBI grant
1K23HL114724. DDM received additional partial salary support by NIH
grants 1U01HL105268-01 and KL2RR031981.
NR 30
TC 75
Z9 76
U1 1
U2 17
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 JUL 11
PY 2015
VL 386
IS 9989
BP 154
EP 162
DI 10.1016/S0140-6736(14)61774-8
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA CM5QC
UT WOS:000357742200032
PM 25960110
ER
PT J
AU Lichtenthal, WG
Corner, GW
Sweeney, CR
Wiener, L
Roberts, KE
Baser, RE
Li, YL
Breitbart, W
Kissane, DW
Prigerson, HG
AF Lichtenthal, Wendy G.
Corner, Geoffrey W.
Sweeney, Corinne R.
Wiener, Lori
Roberts, Kailey E.
Baser, Raymond E.
Li, Yuelin
Breitbart, William
Kissane, David W.
Prigerson, Holly G.
TI Mental Health Services for Parents Who Lost a Child to Cancer: If We
Build Them, Will They Come?
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID PROLONGED GRIEF DISORDER; UNITED-STATES; BEREAVED PARENTS; INTERVENTION;
CAREGIVERS; ATTACHMENT; PATTERNS; BARRIERS; ONTARIO; CARE
AB Purpose
To examine bereavement mental health service use, barriers to use, and factors associated with use in parents bereaved by cancer.
Patients and Methods
A multicenter, cross-sectional study of 120 parents bereaved by cancer between 6 months and 6 years after their loss was performed. Parents completed self-report assessments of mental health service use and barriers, prolonged grief, depression, anxiety, attachment styles, and sense of meaning by phone, in person, or on their own.
Results
Forty-one percent of bereaved parents were currently using mental health services (talk therapy, psychotropic medication, and/or a support group), most commonly within the first 2 years after their loss. Talk therapy was the most frequently used service, although 36% of parents who discontinued therapy did so because it was not helpful. Forty percent of parents who wanted bereavement support reported they were not receiving services. The most common barriers to service use were that it was too painful to speak about the loss (64%) and too difficult to find help (60%). Factors associated with current mental health service use included more recent loss, prior mental health service use, subclinical/increased depression, insecure attachment styles, and a decreased sense of meaning. Minority parents were more likely to have unmet needs than nonminority parents.
Conclusion
Parents appear to need, want, and often access bereavement mental health services, which could be offered in oncology settings. However, barriers to service use must be addressed, particularly for those with more debilitating grief symptoms and for minorities. High treatment dropout rates suggest the importance of improving retention, training providers, and developing effective grief interventions. (C) 2015 by American Society of Clinical Oncology
C1 [Lichtenthal, Wendy G.; Corner, Geoffrey W.; Sweeney, Corinne R.; Roberts, Kailey E.; Baser, Raymond E.; Li, Yuelin; Breitbart, William; Kissane, David W.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA.
[Prigerson, Holly G.] Weill Cornell Med Coll, New York, NY USA.
[Wiener, Lori] NCI, Bethesda, MD 20892 USA.
[Kissane, David W.] Monash Univ, Clayton, Vic, Australia.
RP Lichtenthal, WG (reprint author), Mem Sloan Kettering Canc Ctr, 300 East 66th St, New York, NY 10065 USA.
EM lichtenw@mskcc.org
OI Lichtenthal, Wendy/0000-0003-3597-7826
FU National Cancer Institute [R03 CA139944, K07 CA172216, T32 CA009461, P30
CA08748-48]
FX Supported by National Cancer Institute Grants No. R03 CA139944 (W.G.L.),
K07 CA172216 (W.G.L.), T32 CA009461, and P30 CA08748-48, which provides
partial support for the Behavioral Research Methods Core Facility used
in conducting this investigation.
NR 34
TC 3
Z9 3
U1 1
U2 4
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 JUL 10
PY 2015
VL 33
IS 20
BP 2246
EP U34
DI 10.1200/JCO.2014.59.0406
PG 10
WC Oncology
SC Oncology
GA CR9DM
UT WOS:000361653400004
PM 26033819
ER
PT J
AU Shatz, M
Shats, I
Menendez, D
Resnick, MA
AF Shatz, Maria
Shats, Igor
Menendez, Daniel
Resnick, Michael A.
TI p53 amplifies Toll-like receptor 5 response in human primary and cancer
cells through interaction with multiple signal transduction pathways
SO ONCOTARGET
LA English
DT Article
DE p53; Toll-like receptor 5; cancer; signal transduction; inflammation
ID NF-KAPPA-B; INFLAMMATORY-BOWEL-DISEASE; BREAST-CANCER; NEOADJUVANT
CHEMOTHERAPY; KINASE PATHWAY; LUNG-CANCER; EXPRESSION; ACTIVATION;
AGONIST; GENE
AB The p53 tumor suppressor regulates transcription of genes associated with diverse cellular functions including apoptosis, growth arrest, DNA repair and differentiation. Recently, we established that p53 can modulate expression of Toll-like receptor (TLR) innate immunity genes but the degree of cross-talk between p53 and TLR pathways remained unclear. Here, using gene expression profiling we characterize the global effect of p53 on the TLR5-mediated transcription in MCF7 cells. We found that combined activation of p53 and TLR5 pathways synergistically increases expression of over 200 genes, mostly associated with immunity and inflammation. The synergy was observed in several human cancer cells and primary lymphocytes. The p53-dependent amplification of transcriptional response to TLR5 activation required expression of NF kappa B subunit p65 and was mediated by several molecular mechanisms including increased phosphorylation of p38 MAP kinase, PI3K and STAT3 signaling. Additionally, p53 induction increased cytokine expression in response to TNF alpha, another activator of NF kappa B and MAP kinase pathways, suggesting a broad interaction between p53 and these signaling pathways. The expression of many synergistically induced genes is elevated in breast cancer patients responsive to chemotherapy. We suggest that p53's capacity to enhance immune response could be exploited to increase antitumor immunity and to improve cancer treatment.
C1 [Shatz, Maria; Menendez, Daniel; Resnick, Michael A.] NIEHS, Chromosome Stabil Grp, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Shats, Igor] Duke Univ, Dept Biomed Engn, Durham, NC 27706 USA.
RP Shatz, M (reprint author), NIEHS, Chromosome Stabil Grp, Mol Genet Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM shatzm@niehs.nih.gov
FU Intramural Research Program of the National Institute of Environmental
Health Sciences, NIH [Z01-ES065079]
FX This work was supported by the Intramural Research Program of the
National Institute of Environmental Health Sciences, NIH, Z01-ES065079.
NR 59
TC 2
Z9 3
U1 0
U2 5
PU IMPACT JOURNALS LLC
PI ORCHARD PARK
PA 6666 E QUAKER ST, STE 1, ORCHARD PARK, NY 14127 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD JUL 10
PY 2015
VL 6
IS 19
BP 16963
EP 16980
PG 18
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA CO2VB
UT WOS:000359013600033
PM 26220208
ER
PT J
AU Moore, LV
Thompson, FE
AF Moore, Latetia V.
Thompson, Frances E.
TI Adults Meeting Fruit and Vegetable Intake Recommendations - United
States, 2013
SO MMWR-MORBIDITY AND MORTALITY WEEKLY REPORT
LA English
DT Article
C1 [Moore, Latetia V.] CDC, Div Nutr Phys Act & Obes Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA.
[Thompson, Frances E.] NCI, NIH, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Moore, LV (reprint author), CDC, Div Nutr Phys Act & Obes Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA.
EM lvmoore@cdc.gov
NR 10
TC 17
Z9 17
U1 0
U2 4
PU CENTERS DISEASE CONTROL
PI ATLANTA
PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA
SN 0149-2195
EI 1545-861X
J9 MMWR-MORBID MORTAL W
JI MMWR-Morb. Mortal. Wkly. Rep.
PD JUL 10
PY 2015
VL 64
IS 26
BP 709
EP 713
PG 5
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CN5ET
UT WOS:000358453300001
PM 26158351
ER
PT J
AU Seiler, C
Gebhart, N
Zhang, Y
Shinton, SA
Li, YS
Ross, NL
Liu, XJ
Li, Q
Bilbee, AN
Varshney, GK
LaFave, MC
Burgess, SM
Balciuniene, J
Balciunas, D
Hardy, RR
Kappes, DJ
Wiest, DL
Rhodes, J
AF Seiler, Christoph
Gebhart, Nichole
Zhang, Yong
Shinton, Susan A.
Li, Yue-sheng
Ross, Nicola L.
Liu, Xingjun
Li, Qin
Bilbee, Alison N.
Varshney, Gaurav K.
LaFave, Matthew C.
Burgess, Shawn M.
Balciuniene, Jorune
Balciunas, Darius
Hardy, Richard R.
Kappes, Dietmar J.
Wiest, David L.
Rhodes, Jennifer
TI Mutagenesis Screen Identifies agtpbp1 and eps15L1 as Essential for T
lymphocyte Development in Zebrafish
SO PLOS ONE
LA English
DT Article
ID PURKINJE-CELL DEGENERATION; GENE-EXPRESSION; SACCHAROMYCES-CEREVISIAE;
TRANSGENIC ZEBRAFISH; MUTANT ZEBRAFISH; IMMUNE-SYSTEM; DANIO-RERIO;
GENOME-WIDE; TRANSPOSON; PROTEIN
AB Genetic screens are a powerful tool to discover genes that are important in immune cell development and function. The evolutionarily conserved development of lymphoid cells paired with the genetic tractability of zebrafish make this a powerful model system for this purpose. We used a Tol2-based gene-breaking transposon to induce mutations in the zebrafish (Danio rerio, AB strain) genome, which served the dual purpose of fluorescently tagging cells and tissues that express the disrupted gene and provided a means of identifying the disrupted gene. We identified 12 lines in which hematopoietic tissues expressed green fluorescent protein (GFP) during embryonic development, as detected by microscopy. Subsequent analysis of young adult fish, using a novel approach in which single cell suspensions of whole fish were analyzed by flow cytometry, revealed that 8 of these lines also exhibited GFP expression in young adult cells. An additional 15 lines that did not have embryonic GFP(+) hematopoietic tissue by microscopy, nevertheless exhibited GFP(+) cells in young adults. RT-PCR analysis of purified GFP(+) populations for expression of T and B cell-specific markers identified 18 lines in which T and/or B cells were fluorescently tagged at 6 weeks of age. As transposon insertion is expected to cause gene disruption, these lines can be used to assess the requirement for the disrupted genes in immune cell development. Focusing on the lines with embryonic GFP(+) hematopoietic tissue, we identified three lines in which homozygous mutants exhibited impaired T cell development at 6 days of age. In two of the lines we identified the disrupted genes, agtpbp1 and eps15L1. Morpholino-mediated knockdown of these genes mimicked the T cell defects in the corresponding mutant embryos, demonstrating the previously unrecognized, essential roles of agtpbp1 and eps15L1 in T cell development.
C1 [Seiler, Christoph; Gebhart, Nichole; Zhang, Yong; Shinton, Susan A.; Li, Yue-sheng; Ross, Nicola L.; Liu, Xingjun; Li, Qin; Bilbee, Alison N.; Hardy, Richard R.; Kappes, Dietmar J.; Wiest, David L.; Rhodes, Jennifer] Temple Univ Hlth Syst, Fox Chase Canc Ctr, Blood Cell Dev & Funct Program, Philadelphia, PA 19129 USA.
[Varshney, Gaurav K.; LaFave, Matthew C.; Burgess, Shawn M.] NHGRI, Translat & Funct Genom Branch, NIH, Bethesda, MD 20892 USA.
[Balciuniene, Jorune; Balciunas, Darius] Temple Univ, Dept Biol, Coll Sci & Technol, Philadelphia, PA 19122 USA.
RP Rhodes, J (reprint author), Temple Univ Hlth Syst, Fox Chase Canc Ctr, Blood Cell Dev & Funct Program, Philadelphia, PA 19129 USA.
EM jennifer.rhodes@fccc.edu
OI Wiest, David/0000-0002-0792-3188; LaFave, Matthew/0000-0001-9165-041X;
Varshney, Gaurav K./0000-0002-0429-1904
FU Gabrielle's Angel Foundation [3261601]; National Institutes of Health
[HD061749]; Fox Chase Cancer Center Keystone Blood Cell Development and
Disease
FX This study was supported by (JR) Gabrielle's Angel Foundation 3261601;
(DB) National Institutes of Health HD061749; (DLW and RRH) Fox Chase
Cancer Center Keystone Blood Cell Development and Disease funding. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 61
TC 1
Z9 1
U1 1
U2 9
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 10
PY 2015
VL 10
IS 7
AR e0131908
DI 10.1371/journal.pone.0131908
PG 23
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN1FD
UT WOS:000358162300073
PM 26161877
ER
PT J
AU Fischer, RS
Fowler, VM
AF Fischer, Robert S.
Fowler, Velia M.
TI Thematic Minireview Series: The State of the Cytoskeleton in 2015
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Editorial Material
ID SKELETAL-MUSCLE; ACTIN; FILAMENTS; MECHANICS; PROTEINS; MOTILITY;
HOMOLOG; BINDING; RING; FTSZ
AB The study of cytoskeletal polymers has been an active area of research for more than 70 years. However, despite decades of pioneering work by some of the brightest scientists in biochemistry, cell biology, and physiology, many central questions regarding the polymers themselves are only now starting to be answered. For example, although it has long been appreciated that the actin cytoskeleton provides contractility and couples biochemical responses with mechanical stresses in cells, only recently have we begun to understand how the actin polymer itself responds to mechanical loads. Likewise, although it has long been appreciated that the microtubule cytoskeleton can be post-translationally modified, only recently have the enzymes responsible for these modifications been characterized, so that we can now begin to understand how these modifications alter the polymerization and regulation of microtubule structures. Even the septins in eukaryotes and the cytoskeletal polymers of prokaryotes have yielded new insights due to recent advances in microscopy techniques. In this thematic series of minireviews, these topics are covered by some of the very same scientists who generated these recent insights, thereby providing us with an overview of the State of the Cytoskeleton in 2015.
C1 [Fischer, Robert S.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Fowler, Velia M.] Scripps Res Inst, Dept Cell & Mol Biol, La Jolla, CA 92037 USA.
RP Fischer, RS (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM fischerr2@nhlbi.nih.gov; vfowler@asbmb.org
FU NHLBI NIH HHS [R01 HL083464]
NR 30
TC 7
Z9 7
U1 1
U2 21
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 JUL 10
PY 2015
VL 290
IS 28
BP 17133
EP 17136
DI 10.1074/jbc.R115.663716
PG 4
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CM5MB
UT WOS:000357730900009
PM 25957399
ER
PT J
AU Yu, I
Garnham, CP
Roll-Mecak, A
AF Yu, Ian
Garnham, Christopher P.
Roll-Mecak, Antonina
TI Writing and Reading the Tubulin Code
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Review
ID CHLAMYDOMONAS ALPHA-TUBULIN; BETA-TUBULIN; POSTTRANSLATIONAL
MODIFICATION; TYROSINE-LIGASE; IN-VITRO; AXONEMAL TUBULIN; CYTOSOLIC
CARBOXYPEPTIDASES; MICROTUBULE DYNAMICS; RAT-BRAIN; AXONAL MICROTUBULES
AB Microtubules give rise to intracellular structures with diverse morphologies and dynamics that are crucial for cell division, motility, and differentiation. They are decorated with abundant and chemically diverse posttranslational modifications that modulate their stability and interactions with cellular regulators. These modifications are important for the biogenesis and maintenance of complex microtubule arrays such as those found in spindles, cilia, neuronal processes, and platelets. Here we discuss the nature and subcellular distribution of these posttranslational marks whose patterns have been proposed to constitute a tubulin code that is interpreted by cellular effectors. We review the enzymes responsible for writing the tubulin code, explore their functional consequences, and identify outstanding challenges in deciphering the tubulin code.
C1 [Yu, Ian; Garnham, Christopher P.; Roll-Mecak, Antonina] NINDS, Cell Biol & Biophys Unit, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
[Roll-Mecak, Antonina] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Roll-Mecak, A (reprint author), NIH, Cell Biol & Biophys Unit, Porter Neurosci Res Ctr, Bldg 35,Rm 3B-203,35 Convent Dr,MSC 3700, Bethesda, MD 20892 USA.
EM Antonina@mail.nih.gov
FU National Institutes of Health [1ZIANS003122-05]
FX This work was supported, in whole or in part, by National Institutes of
Health Grant 1ZIANS003122-05 (to A. R. M.). This is the fourth article
in the Thematic Minireview series "The State of the Cytoskeleton in
2015." The authors declare that they have no conflicts of interest with
the contents of this article.
NR 98
TC 28
Z9 28
U1 5
U2 14
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 10
PY 2015
VL 290
IS 28
BP 17163
EP 17172
DI 10.1074/jbc.R115.637447
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CM5MB
UT WOS:000357730900013
PM 25957412
ER
PT J
AU Arao, Y
Coons, LA
Zuercher, WJ
Korach, KS
AF Arao, Yukitomo
Coons, Laurel A.
Zuercher, William J.
Korach, Kenneth S.
TI Transactivation Function-2 of Estrogen Receptor alpha Contains
Transactivation Function-1-regulating Element
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID LIGAND-BINDING DOMAIN; ASPARTATE 351; TAMOXIFEN; ACTIVATION; ANTAGONIST;
PROMOTER; IDENTIFICATION; ANTIESTROGENS; RALOXIFENE; AGONIST
AB ER alpha has a ligand-dependent transactivation function in the ligand binding domain of ER alpha C terminus (AF-2) and a ligand-independent activation function in the N terminus (AF-1). It is still not fully understood how AF-1 and AF-2 activities are regulated cooperatively by ligands. To evaluate the AF-1 involvement in the estrogenic activities of various compounds, we analyzed these transactivation functions using AF-1-truncated and AF-2-mutated ER alpha mutants. AF-2 is composed of two domains with flexible and static regions. We used an AF-2 flexible region mutant and an AF-2 static region mutant. Both mutants have been reported as non-E2 responsive due to disruption of E2-mediated coactivator recruitment to the AF-2. The AF-2 mutants were not activated by agonists, but surprisingly antagonists and selective estrogen receptor modulators (SERMs) activated the AF-2 mutants. This antagonist reversal activity was derived from AF-1. Furthermore, we demonstrated that the AF-2 contains an AF-1 suppression function using C-terminal-truncated ER alpha mutants. From these findings we hypothesized that the mutation of AF-2 disrupted its ability to suppress AF-1, causing the antagonist reversal. To assess the AF-2-mediated AF-1 suppression, we analyzed the transcription activity of physically separated AF-1 and AF-2 using a novel hybrid reporter assay. We observed that the AF-1 activity was not suppressed by the physically separated AF-2. Furthermore, SERMs did not induce the AF-1-mediated activity from the separated mutant AF-2, which differed from the intact protein. These results imply that SERM activity is dependent on a conformational change of the full-length ER alpha molecule, which allows for AF-1 activation.
C1 [Arao, Yukitomo; Coons, Laurel A.; Korach, Kenneth S.] NIEHS, Receptor Biol Sect, Reprod & Dev Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Coons, Laurel A.] Duke Univ, Dept Pharmacol & Canc Biol, Med Ctr, Durham, NC 27710 USA.
[Zuercher, William J.] GlaxoSmithKline, Dept Biol Chem, Res Triangle Pk, NC 27709 USA.
RP Korach, KS (reprint author), 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM korach@niehs.nih.gov
OI Korach, Kenneth/0000-0002-7765-418X
FU National Institutes of Health (Division of Intramural Research of the
NIEHS) [Z01ES70065]
FX This work was supported, in whole or in part, by National Institutes of
Health Grant Z01ES70065 (Division of Intramural Research of the NIEHS;
to K. S. K.). The authors declare that they have no conflicts of
interest with the contents of this article.
NR 28
TC 2
Z9 2
U1 2
U2 7
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 10
PY 2015
VL 290
IS 28
BP 17611
EP 17627
DI 10.1074/jbc.M115.638650
PG 17
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CM5MB
UT WOS:000357730900051
PM 26028650
ER
PT J
AU Mascola, JR
AF Mascola, John R.
TI The modern era of HIV-1 vaccine development
SO SCIENCE
LA English
DT Editorial Material
ID NEUTRALIZING ANTIBODIES; IMMUNIZATION; ENV
C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Mascola, JR (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM jmascola@mail.nih.gov
NR 14
TC 12
Z9 12
U1 4
U2 19
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 JUL 10
PY 2015
VL 349
IS 6244
BP 139
EP 140
DI 10.1126/science.aac7800
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CM4OM
UT WOS:000357664300022
PM 26160931
ER
PT J
AU Ahn, DH
Li, JN
Wei, L
Doyle, A
Marshall, JL
Schaaf, LJ
Phelps, MA
Villalona-Calero, MA
Bekaii-Saab, T
AF Ahn, Daniel H.
Li, Junan
Wei, Lai
Doyle, Austin
Marshall, John L.
Schaaf, Larry J.
Phelps, Mitch A.
Villalona-Calero, Miguel A.
Bekaii-Saab, Tanios
TI Results of an abbreviated phase-II study with the Akt Inhibitor MK-2206
in Patients with Advanced Biliary Cancer
SO SCIENTIFIC REPORTS
LA English
DT Article
ID TRACT CANCER; SOLID TUMORS; CHOLANGIOCARCINOMA; POLYMORPHISMS;
GEMCITABINE; ACTIVATION; PHARMACOKINETICS; 5-FLUOROURACIL; TRASTUZUMAB;
COMBINATION
AB Biliary cancers (BC) are rare, chemoresistant and are associated with a poor prognosis. Targeting the Akt pathway is of significance in BC. We hypothesized that the allosteric inhibitor MK-2206 will be active in BC. This was a multi-institutional phase II study of MK-2206 given to patients with advanced, refractory BC. The primary end point was overall response rate. We also characterized pharmacokinetic profiles of MK-2206 in these patients and explored its potential correlation with clinical outcomes. Eight patients were enrolled prior to early termination of the trial. All patients had received prior systemic therapy. The best response observed was stable disease, exceeding 12 weeks in two patients. Toxicities were mild and tolerable. MK-2206 exhibited a pharmacokinetic profile with an apparent slow absorption followed by biphasic elimination in these patients with BC. No significant association was observed between the pharmacokinetic properties of MK-2206 and clinical outcomes. MK-2206 as a single-agent in BC is tolerable with pharmacokinetic properties similar to patients with other solid tumors. No clinical activity was observed in this limited population. Further development of Akt inhibitors may need to focus on combinations with other molecular targeted agents, conventional cytotoxic chemotherapy and prospective patient selection.
C1 [Ahn, Daniel H.; Villalona-Calero, Miguel A.; Bekaii-Saab, Tanios] Ohio State Univ, Div Med Oncol, Ctr Comprehens Canc, Columbus, OH 43210 USA.
[Li, Junan; Schaaf, Larry J.; Phelps, Mitch A.] Ohio State Univ, Coll Pharm, Columbus, OH 43210 USA.
[Wei, Lai] Ohio State Univ, Ctr Biostat, Columbus, OH 43210 USA.
[Doyle, Austin] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Marshall, John L.] Lombardi Comprehens Canc Ctr, Div Hematol Oncol, Washington, DC 20057 USA.
RP Bekaii-Saab, T (reprint author), Ohio State Univ, Div Med Oncol, Ctr Comprehens Canc, 300 W 10th Ave, Columbus, OH 43210 USA.
EM tanios.saab@osumc.edu
FU NCI [N01 HHSN261201100070C]
FX This study was supported in part by NCI N01 HHSN261201100070C to MAV.
NR 31
TC 4
Z9 4
U1 2
U2 4
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 JUL 10
PY 2015
VL 5
AR 12122
DI 10.1038/srep12122
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CM5HJ
UT WOS:000357717600001
PM 26161813
ER
PT J
AU Medina, SH
Schneider, JP
AF Medina, Scott H.
Schneider, Joel P.
TI Cancer cell surface induced peptide folding allows intracellular
translocation of drug
SO JOURNAL OF CONTROLLED RELEASE
LA English
DT Article
DE Cell-penetrating peptide; Translocation; Biodistribution; Drug delivery;
Paclitaxel; In vivo efficacy
ID BETA-HAIRPIN PEPTIDES; PENETRATING PEPTIDES; MEDIATED ENDOCYTOSIS;
MEMBRANE PEPTIDE; IN-VIVO; DELIVERY; MECHANISM; PACLITAXEL; PROTEIN;
LINES
AB Many lead molecules identified in drug discovery campaigns are eliminated from consideration due to poor solubility and low cell permeability. These orphaned molecules could have clinical value if solubilized and delivered properly. SVS-1 is a de novo designed peptide that preferentially folds at the surface of tumor cells, adopting a beta-hairpin conformation that rapidly translocates into the cytoplasm, and ultimately nucleus, of cells. SVS-1 is stable in serum and small molecules attached to the peptide are effectively delivered to cancer cells via mechanisms involving physical translocation and, to a lesser extent, clathrin-dependent endocytosis. For example, ligating the model hydrophobic drug Paclitaxel (PTX) to SVS-1 improved its aqueous solubility by similar to 1000-fold and successfully delivered and released PTX to cancer cells in vitro and tumors in vivo without toxic adjuvants. These results suggest that SVS-1 can serve as a simple, effective delivery platform for molecules with poor solubility and permeability. Published by Elsevier B.V.
C1 [Medina, Scott H.; Schneider, Joel P.] NCI, Biol Chem Lab, NIH, Frederick, MD 21702 USA.
RP Schneider, JP (reprint author), NCI, 376 Boyle St, Frederick, MD 21702 USA.
EM Joel.Schneider@nih.gov
FU Intramural Research Program of the National Cancer Institute, National
Institutes of Health [BC011313]
FX We thank Dr. Christopher Nelson and Dr. Gary Pauly for providing
valuable synthetic intermediates. Research funding was provided by the
Intramural Research Program of the National Cancer Institute, National
Institutes of Health (Project #: BC011313).
NR 46
TC 5
Z9 5
U1 4
U2 22
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-3659
EI 1873-4995
J9 J CONTROL RELEASE
JI J. Control. Release
PD JUL 10
PY 2015
VL 209
BP 317
EP 326
DI 10.1016/j.jconrel.2015.05.267
PG 10
WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA CJ7KQ
UT WOS:000355674300032
PM 25979324
ER
PT J
AU Nishiura, H
Miyamatsu, Y
Chowell, G
Saitoh, M
AF Nishiura, H.
Miyamatsu, Y.
Chowell, G.
Saitoh, M.
TI Assessing the risk of observing multiple generations of Middle East
respiratory syndrome (MERS) cases given an imported case
SO EUROSURVEILLANCE
LA English
DT Article
ID CORONAVIRUS INFECTIONS; COV; TRANSMISSIBILITY; SURVEILLANCE
AB To guide risk assessment, expected numbers of cases and generations were estimated, assuming a case importation of Middle East respiratory syndrome (MERS). Our analysis of 36 importation events yielded the risk of observing secondary transmission events at 22.7% (95% confidence interval: 19.3-25.1). The risks of observing generations 2, 3 and 4 were estimated at 10.5%, 6.1% and 3.9%, respectively. Countries at risk should be ready for highly variable outcomes following an importation of MERS.
C1 [Nishiura, H.; Miyamatsu, Y.; Saitoh, M.] Univ Tokyo, Grad Sch Med, Tokyo, Japan.
[Nishiura, H.; Miyamatsu, Y.; Saitoh, M.] Japan Sci & Technol Agcy, CREST, Saitama, Japan.
[Chowell, G.] Georgia State Univ, Sch Publ Hlth, Atlanta, GA 30303 USA.
[Chowell, G.] Fogarty Int Ctr, Div Int Epidemiol & Populat Studies, NIH, Bethesda, MD USA.
Inst Stat Math, Tachikawa, Tokyo, Japan.
RP Nishiura, H (reprint author), Univ Tokyo, Grad Sch Med, Tokyo, Japan.
EM nishiurah@gmail.com
OI Nishiura, Hiroshi/0000-0003-0941-8537
FU Japan Society for the Promotion of Science (JSPS) KAKENHI [26670308,
26700028]; Japan Agency for Medical Research and Development; Japan
Science and Technology Agency (JST) CREST program; RISTEX program for
Science of Science, Technology and Innovation Policy; Division of
International Epidemiology and Population Studies, Fogarty International
Center, United States National Institutes of Health; Office of Pandemics
and Emerging Threats at the United States Department of Health and Human
Services; NSF, joint NSF-NIH-USDA Ecology and Evolution of Infectious
Diseases programme [1414374]; United Kingdom Biotechnology and
Biological Sciences Research Council grant [BB/M008894/1]; NSF-IIS Grant
[1518939]
FX HN received funding support from the Japan Society for the Promotion of
Science (JSPS) KAKENHI Grant Numbers 26670308 and 26700028, Japan Agency
for Medical Research and Development, the Japan Science and Technology
Agency (JST) CREST program and RISTEX program for Science of Science,
Technology and Innovation Policy. GC acknowledge financial support from
the Division of International Epidemiology and Population Studies, The
Fogarty International Center, United States National Institutes of
Health, funded in part by the Office of Pandemics and Emerging Threats
at the United States Department of Health and Human Services, as well as
support from grants NSF grant 1414374 as part of the joint NSF-NIH-USDA
Ecology and Evolution of Infectious Diseases programme, United Kingdom
Biotechnology and Biological Sciences Research Council grant
BB/M008894/1 and NSF-IIS Grant# 1518939. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 20
TC 6
Z9 6
U1 0
U2 0
PU EUR CENTRE DIS PREVENTION & CONTROL
PI STOCKHOLM
PA TOMTEBODAVAGEN 11A, STOCKHOLM, 171 83, SWEDEN
SN 1560-7917
J9 EUROSURVEILLANCE
JI Eurosurveillance
PD JUL 9
PY 2015
VL 20
IS 27
BP 6
EP 11
AR 21181
PG 6
WC Infectious Diseases
SC Infectious Diseases
GA CM8VI
UT WOS:000357979900002
ER
PT J
AU Miliani, K
Migueres, B
Verjat-Trannoy, D
Thiolet, JM
Vaux, S
Astagneau, P
AF Miliani, K.
Migueres, B.
Verjat-Trannoy, D.
Thiolet, J. M.
Vaux, S.
Astagneau, P.
CA French Prevalence Survey Study Grp
TI National point prevalence survey of healthcare-associated infections and
antimicrobial use in French home care settings, May to June 2012
SO EUROSURVEILLANCE
LA English
DT Article
ID EUROPEAN NURSING-HOMES; SURVEILLANCE
AB In May and June 2012, a national point prevalence survey (PPS) of healthcare-associated infections (HAIs) and antimicrobial use was conducted among French patients under home-based hospital care (HBHC). Data from 5,954 patients in 179 volunteer HBHC providers were collected. Prevalence of patients with at least one active HAI was 6.8% (95% confidence interval (CI): 6.1-7.4). Prevalence of those receiving at least one antimicrobial agent was 15.2% (95% CI: 14.3-16.1). More than a third (35.5%) of HAIs were HBHC-associated, 56% were imported from a healthcare facility and 8.5% of indeterminate origin. The main infection sites were urinary tract (26.6%), skin and soft tissue (17.6%), surgical site (15%), and pneumonia or other respiratory tract infections (13.5%). In multivariate analysis, three risk factors were associated with HBHC-associated infections: urinary catheter, at least one vascular catheter and a McCabe score 1 or 2. The most frequently isolated microorganism was Staphylococcus aureus (20.7%), 28.1% of them meticillin-resistant. Non-susceptibility to third-generation cephalosporins was reported in 25.3% of Enterobacteriaceae, of which 16.1% were extended spectrum beta-lactamase-producing strains. The most prescribed antimicrobials were fluoroquinolones (16.1%), and third-generation cephalosporins (14.5%). PPS may be a good start in HBHC to obtain information on epidemiology of HAIs and antimicrobial use.
C1 [Miliani, K.; Migueres, B.; Verjat-Trannoy, D.; Astagneau, P.] Univ Tokyo, Grad Sch Med, Tokyo, Japan.
[Migueres, B.] Japan Sci & Technol Agcy, CREST, Saitama, Japan.
[Thiolet, J. M.; Vaux, S.] Georgia State Univ, Sch Publ Hlth, Atlanta, GA 30303 USA.
[Astagneau, P.] NIH, Fogarty Int Ctr, Div Int Epidemiol & Populat Studies, Bethesda, MD 20892 USA.
[French Prevalence Survey Study Grp] Inst Stat Math, Tachikawa, Tokyo, Japan.
RP Miliani, K (reprint author), Univ Tokyo, Grad Sch Med, Tokyo, Japan.
EM katiuska.miliani@sap.aphp.fr
FU French Institute for Public Health Surveillance (Institut de Veille
Sanitaire, InVS), Saint Maurice, France
FX Grants were received from the French Institute for Public Health
Surveillance (Institut de Veille Sanitaire, InVS), Saint Maurice,
France.
NR 26
TC 0
Z9 0
U1 2
U2 4
PU EUR CENTRE DIS PREVENTION & CONTROL
PI STOCKHOLM
PA TOMTEBODAVAGEN 11A, STOCKHOLM, 171 83, SWEDEN
SN 1560-7917
J9 EUROSURVEILLANCE
JI Eurosurveillance
PD JUL 9
PY 2015
VL 20
IS 27
BP 12
EP 22
AR 21182
PG 11
WC Infectious Diseases
SC Infectious Diseases
GA CM8VI
UT WOS:000357979900003
ER
PT J
AU Ghosh, AK
Yu, XF
Osswald, HL
Agniswamy, J
Wang, YF
Arnano, M
Weber, IT
Mitsuya, H
AF Ghosh, Arun K.
Yu, Xufen
Osswald, Heather L.
Agniswamy, Johnson
Wang, Yuan-Fang
Arnano, Masayuki
Weber, Irene T.
Mitsuya, Hiroaki
TI Structure-Based Design of Potent HIV-1 Protease Inhibitors with Modified
P1-Biphenyl Ligands: Synthesis, Biological Evaluation, and
Enzyme-Inhibitor X-ray Structural Studies
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; RESOLUTION CRYSTAL-STRUCTURES;
DRUG-RESISTANT MUTANTS; IN-VITRO; COMPLEXES; TETRAHYDROFURAN; DARUNAVIR;
VARIANTS; BACKBONE; GRL-0519
AB We report the design, synthesis, X-ray structural studies, and biological evaluation of a novel series of HIV-1 protease inhibitors. We designed a variety of functionalized biphenyl derivatives to make enhanced van der Waals interactions in the Si subsite of HIV-1 protease. These biphenyl derivatives were conveniently synthesized using a Suzuki-Miyaura cross-coupling reaction as the key step. We examined the potential of these functionalized biphenyl-derived P1 ligands in combination with 3-(S)-tetrahydrofuranyl urethane and bis-tetrahydrofuranyl urethane as the P2 ligands. Inhibitor 21e, with a 2-methoxy-1,1'-biphenyl derivative as P1 ligand and bis-THF as the P2 ligand, displayed the most potent enzyme inhibitory and antiviral activity. This inhibitor also exhibited potent activity against a panel of multidrug-resistant HIV-1 variants. A high resolution X-ray crystal structure of related Boc-derivative 17a-bound HIV-1 protease provided important molecular insight into the ligand-binding site interactions of the biphenyl core in the Si subsite of HIV-1 protease.
C1 [Ghosh, Arun K.; Yu, Xufen; Osswald, Heather L.] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA.
[Ghosh, Arun K.; Yu, Xufen; Osswald, Heather L.] Purdue Univ, Dept Med Chem, W Lafayette, IN 47907 USA.
[Agniswamy, Johnson; Wang, Yuan-Fang; Weber, Irene T.] Georgia State Univ, Dept Biol, Mol Basis Dis, Atlanta, GA 30303 USA.
[Arnano, Masayuki; Mitsuya, Hiroaki] Kumamoto Univ, Grad Sch Med & Pharmaceut Sci, Dept Hematol, Kumamoto 8608556, Japan.
[Arnano, Masayuki; Mitsuya, Hiroaki] Kumamoto Univ, Grad Sch Med & Pharmaceut Sci, Dept Infect Dis, Kumamoto 8608556, Japan.
[Mitsuya, Hiroaki] NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA.
[Mitsuya, Hiroaki] Natl Ctr Global Hlth & Med, Ctr Clin Sci, Tokyo 1628655, Japan.
RP Ghosh, AK (reprint author), Purdue Univ, Dept Chem, 560 Oval Dr, W Lafayette, IN 47907 USA.
EM akghosh@purdue.edu
RI Amano, Masayuki/N-7407-2016
OI Amano, Masayuki/0000-0003-0516-9502
FU National Institutes of Health [GM53386, GM62920]; U.S. Department of
Energy, Basic Energy Sciences, Office of Science [W-31-109-Eng-38];
Intramural Research Program of the Center for Cancer Research, National
Cancer Institute, National Institutes of Health; Ministry of Education,
Culture, Sports, Science, and Technology of Japan (Monbu Kagakusho);
Ministry of Health, Welfare, and Labor of Japan
FX This research was supported by the National Institutes of Health (grant
GM53386, A.K.G., and grant GM62920, I.T.W.). X-ray data were collected
at the Southeast Regional Collaborative Access Team (SER-CAT) beamline
22BM at the Advanced Photon Source, Argonne National Laboratory. Use of
the Advanced Photon Source was supported by the U.S. Department of
Energy, Basic Energy Sciences, Office of Science, under contract no.
W-31-109-Eng-38. This work was also supported by the Intramural Research
Program of the Center for Cancer Research, National Cancer Institute,
National Institutes of Health, and in part by a Grant-in-Aid for
Scientific Research (Priority Areas) from the Ministry of Education,
Culture, Sports, Science, and Technology of Japan (Monbu Kagakusho), a
Grant for Promotion of AIDS Research from the Ministry of Health,
Welfare, and Labor of Japan, and the Grant to the Cooperative Research
Project on Clinical and Epidemiological Studies of Emerging and
Reemerging Infectious Diseases (Renkei Jigyo) of Monbu-Kagakusho. We
thank the Purdue University Center for Cancer Research, which supports
the shared NMR and mass spectrometry facilities.
NR 37
TC 7
Z9 7
U1 2
U2 16
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
EI 1520-4804
J9 J MED CHEM
JI J. Med. Chem.
PD JUL 9
PY 2015
VL 58
IS 13
BP 5334
EP 5343
DI 10.1021/acs.jmedchem.5b00676
PG 10
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA CM8PE
UT WOS:000357963300014
PM 26107245
ER
PT J
AU Knepper, MA
Kwon, TH
Nielsen, S
AF Knepper, Mark A.
Kwon, Tae-Hwan
Nielsen, Soren
TI Molecular Physiology of Water Balance Reply
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
ID DESCENDING VASA-RECTA
C1 [Knepper, Mark A.] NHLBI, Bethesda, MD 20892 USA.
[Kwon, Tae-Hwan] Kyungpook Natl Univ, Taegu 702701, South Korea.
[Nielsen, Soren] Aalborg Univ, Aalborg, Denmark.
RP Knepper, MA (reprint author), NHLBI, Bldg 10, Bethesda, MD 20892 USA.
EM knep@helix.nih.gov
NR 3
TC 3
Z9 3
U1 0
U2 2
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUL 9
PY 2015
VL 373
IS 2
BP 196
EP 196
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA CM3QP
UT WOS:000357598600027
PM 26154805
ER
PT J
AU Bedford, T
Riley, S
Barr, IG
Broor, S
Chadha, M
Cox, NJ
Daniels, RS
Gunasekaran, CP
Hurt, AC
Kelso, A
Klimov, A
Lewis, NS
Li, XY
McCauley, JW
Odagiri, T
Potdar, V
Rambaut, A
Shu, YL
Skepner, E
Smith, DJ
Suchard, MA
Tashiro, M
Wang, DY
Xu, XY
Lemey, P
Russell, CA
AF Bedford, Trevor
Riley, Steven
Barr, Ian G.
Broor, Shobha
Chadha, Mandeep
Cox, Nancy J.
Daniels, Rodney S.
Gunasekaran, C. Palani
Hurt, Aeron C.
Kelso, Anne
Klimov, Alexander
Lewis, Nicola S.
Li, Xiyan
McCauley, John W.
Odagiri, Takato
Potdar, Varsha
Rambaut, Andrew
Shu, Yuelong
Skepner, Eugene
Smith, Derek J.
Suchard, Marc A.
Tashiro, Masato
Wang, Dayan
Xu, Xiyan
Lemey, Philippe
Russell, Colin A.
TI Global circulation patterns of seasonal influenza viruses vary with
antigenic drift
SO NATURE
LA English
DT Article
ID A VIRUS; B VIRUS; SELECTION; DYNAMICS; EPIDEMIOLOGY; NETWORK; SPREAD;
STATES; SITES; WAVES
AB Understanding the spatiotemporal patterns of emergence and circulation of new human seasonal influenza virus variants is a key scientific and public health challenge. The global circulation patterns of influenza A/H3N2 viruses are well characterized(1-7), but the patterns of A/H1N1 and B viruses have remained largely unexplored. Here we show that the global circulation patterns of A/H1N1 (up to 2009), B/Victoria, and B/Yamagata viruses differ substantially from those of A/H3N2 viruses, on the basis of analyses of 9,604 haemagglutinin sequences of human seasonal influenza viruses from 2000 to 2012. Whereas genetic variants of A/H3N2 viruses did not persist locally between epidemics and were reseeded from East and Southeast Asia, genetic variants of A/H1N1 and B viruses persisted across several seasons and exhibited complex global dynamics with East and Southeast Asia playing a limited role in disseminating new variants. The less frequent global movement of influenza A/H1N1 and B viruses coincided with slower rates of antigenic evolution, lower ages of infection, and smaller, less frequent epidemics compared to A/H3N2 viruses. Detailed epidemic models support differences in age of infection, combined with the less frequent travel of children, as probable drivers of the differences in the patterns of global circulation, suggesting a complex interaction between virus evolution, epidemiology, and human behaviour.
C1 [Bedford, Trevor] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98109 USA.
[Riley, Steven] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Infect Dis Epidemiol, MRC Ctr Outbreak Anal & Modelling, London SW7 2AZ, England.
[Riley, Steven; Rambaut, Andrew] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Barr, Ian G.; Hurt, Aeron C.; Kelso, Anne] WHO, Collaborating Ctr Reference & Res Influenza, Melbourne, Vic 3000, Australia.
[Broor, Shobha] SGT Med Coll Hosp & Res Inst, Gurgaon 122505, Haryana, India.
[Chadha, Mandeep; Potdar, Varsha] Natl Inst Virol, Pune 411001, Maharashtra, India.
[Cox, Nancy J.; Klimov, Alexander; Xu, Xiyan] Ctr Dis Control & Prevent, WHO Collaborating Ctr Reference & Res Influenza, Atlanta, GA 30329 USA.
[Daniels, Rodney S.; McCauley, John W.] Natl Inst Med Res, MRC, WHO Collaborating Ctr Reference & Res Influenza, London NW7 1AA, England.
[Gunasekaran, C. Palani] King Inst Prevent Med & Res, Madras 600032, Tamil Nadu, India.
[Hurt, Aeron C.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Parkville, Vic 3010, Australia.
[Lewis, Nicola S.; Skepner, Eugene; Smith, Derek J.] Univ Cambridge, Dept Zool, Cambridge CB2 3EJ, England.
[Li, Xiyan; Shu, Yuelong; Wang, Dayan] China CDC, WHO Collaborating Ctr Reference & Res Influenza, Natl Inst Viral Dis Control & Prevent, Beijing 102206, Peoples R China.
[Odagiri, Takato; Tashiro, Masato] Natl Inst Infect Dis, WHO Collaborating Ctr Reference & Res Influenza, Tokyo 2080011, Japan.
[Rambaut, Andrew] Univ Edinburgh, Inst Evolutionary Biol, Edinburgh EH9 3JT, Midlothian, Scotland.
[Rambaut, Andrew] Univ Edinburgh, Ctr Immunol Infect & Evolut, Edinburgh EH9 3FL, Midlothian, Scotland.
[Smith, Derek J.] Erasmus MC, Dept Virosci, NL-3015 Rotterdam, Netherlands.
[Suchard, Marc A.] Univ Calif Los Angeles, Dept Biostat, Fielding Sch Publ Hlth, Los Angeles, CA 90095 USA.
[Suchard, Marc A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biomath, Los Angeles, CA 90095 USA.
[Suchard, Marc A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA.
[Lemey, Philippe] KU Leuven Univ Leuven, Rega Inst, Dept Microbiol & Immunol, B-3000 Leuven, Belgium.
[Russell, Colin A.] Univ Cambridge, Dept Vet Med, Cambridge CB3 0ES, England.
RP Russell, CA (reprint author), Univ Cambridge, Dept Vet Med, Cambridge CB3 0ES, England.
EM car44@cam.ac.uk
OI Russell, Colin/0000-0002-2113-162X; Barr, Ian/0000-0002-7351-418X; Hurt,
Aeron/0000-0003-1826-4314
FU Newton International Fellowship from the Royal Society; National
Institutes of Health (NIH) [U54 GM111274]; Medical Research Council (UK)
[MR/J008761/1]; Wellcome Trust (UK) [093488/Z/10/Z]; Fogarty
International Centre (USA) [R01 TW008246-01]; Department of Homeland
Security (USA, RAPIDD program); National Institute of General Medical
Sciences (USA) [MIDAS U01 GM110721-01]; National Institute for Health
Research (UK, Health Protection Research Unit); Australian Government
Department of Health; US Department of Health and Human Services;
National Science Foundation DMS [1264153]; NIH [R01 AI 107034]; EU
[278433-PREDEMICS]; ERC [260864]; Royal Society; [U117512723]
FX We thank National Influenza Centres worldwide for their contributions to
influenza virus surveillance. T.B. was supported by a Newton
International Fellowship from the Royal Society and through National
Institutes of Health (NIH) U54 GM111274. S.R. was supported by Medical
Research Council (UK, Project MR/J008761/1), Wellcome Trust (UK, Project
093488/Z/10/Z), Fogarty International Centre (USA, R01 TW008246-01),
Department of Homeland Security (USA, RAPIDD program), National
Institute of General Medical Sciences (USA, MIDAS U01 GM110721-01) and
National Institute for Health Research (UK, Health Protection Research
Unit funding). The Melbourne WHO Collaborating Centre for Reference and
Research on Influenza was supported by the Australian Government
Department of Health and thanks N. Komadina and Y.-M. Deng. The Atlanta
WHO Collaborating Center for Surveillance, Epidemiology and Control of
Influenza was supported by the US Department of Health and Human
Services. NIV thanks A.C. Mishra, M. Chawla-Sarkar, A. M. Abraham, D.
Biswas, S. Shrikhande, B. AnuKumar, and A. Jain. Influenza surveillance
in India was expanded, in part, through US Cooperative Agreements
(5U50C1024407 and U51IP000333) and by the Indian Council of Medical
Research. M. A. S. was supported through National Science Foundation DMS
1264153 and NIH R01 AI 107034. Work of the WHO Collaborating Centre for
Reference and Research on Influenza at the MRC National Institute for
Medical Research was supported by U117512723. P.L., A.R. & M.A.S were
supported by EU Seventh Framework Programme [FP7/2007-2013] under Grant
Agreement no. 278433-PREDEMICS and ERC Grant agreement no. 260864.
C.A.R. was supported by a University Research Fellowship from the Royal
Society.
NR 38
TC 44
Z9 46
U1 8
U2 36
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 JUL 9
PY 2015
VL 523
IS 7559
BP 217
EP U206
DI 10.1038/nature14460
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CM4ZO
UT WOS:000357695900036
PM 26053121
ER
PT J
AU Lubick, KJ
Robertson, SJ
McNally, KL
Freedman, BA
Rasmussen, AL
Taylor, RT
Walts, AD
Tsuruda, S
Sakai, M
Ishizuka, M
Boer, EF
Foster, EC
Chiramel, AI
Addison, CB
Green, R
Kastner, DL
Katze, MG
Holland, SM
Forlino, A
Freeman, AF
Boehm, M
Yoshii, K
Best, SM
AF Lubick, Kirk J.
Robertson, Shelly J.
McNally, Kristin L.
Freedman, Brett A.
Rasmussen, Angela L.
Taylor, R. Travis
Walts, Avram D.
Tsuruda, Seitaro
Sakai, Mizuki
Ishizuka, Mariko
Boer, Elena F.
Foster, Erin C.
Chiramel, Abhilash I.
Addison, Conrad B.
Green, Richard
Kastner, Daniel L.
Katze, Michael G.
Holland, Steven M.
Forlino, Antonella
Freeman, Alexandra F.
Boehm, Manfred
Yoshii, Kentaro
Best, Sonja M.
TI Flavivirus Antagonism of Type I Interferon Signaling Reveals Prolidase
as a Regulator of IFNAR1 Surface Expression
SO CELL HOST & MICROBE
LA English
DT Article
ID VIRUS NS5; ALPHA RECEPTOR; PROTEIN; DEFICIENCY; PHOSPHORYLATION;
IDENTIFICATION; DEGRADATION; MUTATIONS
AB Type I interferon (IFN-alpha/beta or IFN-I) signals through two receptor subunits, IFNAR1 and IFNAR2, to orchestrate sterile and infectious immunity. Cellular pathways that regulate IFNAR1 are often targeted by viruses to suppress the antiviral effects of IFN-I. Here we report that encephalitic flaviviruses, including tick-borne encephalitis virus and West Nile virus, antagonize IFN-I signaling by inhibiting IFNAR1 surface expression. Loss of IFNAR1 was associated with binding of the viral IFN-I antagonist, NS5, to prolidase (PEPD), a cellular dipeptidase implicated in primary immune deficiencies in humans. Prolidase was required for IFNAR1 maturation and accumulation, activation of IFN beta-stimulated gene induction, and IFN-I-dependent viral control. Human fibroblasts derived from patients with genetic prolidase deficiency exhibited decreased IFNAR1 surface expression and reduced IFN beta-stimulated signaling. Thus, by understanding flavivirus IFN-I antagonism, prolidase is revealed as a central regulator of IFN-I responses.
C1 [Lubick, Kirk J.; Robertson, Shelly J.; McNally, Kristin L.; Freedman, Brett A.; Boer, Elena F.; Foster, Erin C.; Chiramel, Abhilash I.; Addison, Conrad B.; Best, Sonja M.] NIAID, Virus Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
[Rasmussen, Angela L.; Green, Richard; Katze, Michael G.] Univ Washington, Dept Microbiol, Seattle, WA 98109 USA.
[Taylor, R. Travis] Univ Toledo, Coll Med, Dept Med Microbiol & Immunol, Toledo, OH 43614 USA.
[Walts, Avram D.] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA.
[Tsuruda, Seitaro; Sakai, Mizuki; Ishizuka, Mariko; Yoshii, Kentaro] Hokkaido Univ, Grad Sch Vet Med, Publ Hlth Lab, Sapporo, Hokkaido 0600818, Japan.
[Kastner, Daniel L.] NHGRI, Metab Cardiovasc & Inflammatory Dis Genom Branch, NIH, Bethesda, MD 20892 USA.
[Holland, Steven M.; Freeman, Alexandra F.] NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20814 USA.
[Forlino, Antonella] Univ Pavia, Biochem Unit, Dept Mol Med, I-27100 Pavia, Italy.
RP Best, SM (reprint author), NIAID, Virus Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
EM sbest@niaid.nih.gov
RI YOSHII, Kentaro/A-4808-2012;
OI Rasmussen, Angela/0000-0001-9462-3169
FU Intramural Research Program of the National Institutes of Health; NIAID;
NHGRI; NHLBI, Italian Cariplo [2011-0270]; NIAID/NIH Grant [U19
AI109761]; Ministry of Education, Culture, Sports, Sciences and
Technology of Japan [22780268, 24780293, 26660220]; Akiyama Life Science
Foundation
FX We thank the PD patients and families for their participation in this
study. This work was supported by the Intramural Research Program of the
National Institutes of Health, NIAID, NHGRI and the NHLBI, Italian
Cariplo 2011-0270 to A.F., NIAID/NIH Grant U19 AI109761 to M.G.K, and
Grants-in-Aid for Scientific Research (22780268, 24780293, and 26660220)
from the Ministry of Education, Culture, Sports, Sciences and Technology
of Japan and The Akiyama Life Science Foundation to K.Y.
NR 36
TC 8
Z9 8
U1 0
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1931-3128
EI 1934-6069
J9 CELL HOST MICROBE
JI Cell Host Microbe
PD JUL 8
PY 2015
VL 18
IS 1
BP 61
EP 74
DI 10.1016/j.chom.2015.06.007
PG 14
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA CM4WS
UT WOS:000357687000011
PM 26159719
ER
PT J
AU Shin, HJ
Rashid, MA
Canner, LK
Bokesch, HR
Wilson, JA
McMahon, JB
Gustafson, KR
AF Shin, Hee Jae
Rashid, Mohammad A.
Canner, Laura K.
Bokesch, Heidi R.
Wilson, Jennifer A.
McMahon, James B.
Gustafson, Kirk R.
TI Stellettapeptins A and B, HIV-inhibitory cyclic depsipeptides from the
marine sponge Stelletta sp.
SO TETRAHEDRON LETTERS
LA English
DT Article
DE Depsipeptide; Sponge peptide; Stelletta; Anti-HIV
ID PAPUA-NEW-GUINEA; ASYMMETRIC-SYNTHESIS; CALLIPELTIN-A;
ABSOLUTE-CONFIGURATION; LATRUNCULIA SP; ACIDS; MIRABILIS; PEPTIDES
AB Two new HIV-inhibitory depsipeptides, stellettapeptins A (1) and B (2), were isolated from an extract of the marine sponge Stelletta sp., collected from northwestern Australia. Structures of these cyclic nonribosomal peptides were elucidated on the basis of extensive NMR data analysis, and chemical degradation and derivatization studies. Stellettapeptins contain numerous nonproteinogenic amino acid residues and they are the first peptides reported to contain a 3-hydroxy-6,8-dimethylnon-4-(Z)-enoic acid moiety. Compounds 1 and 2 potently inhibit infection of human T-lymphoblastoid cells by HIV-I-RF with EC50 values of 23 and 27 nM, respectively. Published by Elsevier Ltd.
C1 [Shin, Hee Jae; Rashid, Mohammad A.; Canner, Laura K.; Bokesch, Heidi R.; Wilson, Jennifer A.; McMahon, James B.; Gustafson, Kirk R.] NCI, Mol Targets Lab, Ctr Canc Res, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Canner, Laura K.; Bokesch, Heidi R.] Leidos Biomed Res Inc, Basic Sci Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
RP Gustafson, KR (reprint author), NCI, Mol Targets Lab, Ctr Canc Res, Frederick Natl Lab Canc Res, Bldg 562,Room 201, Frederick, MD 21702 USA.
EM shinhj@kiost.ac; rashidma@univdhaka.edu; gustafki@mail.nih.gov
FU Frederick National Laboratory for Cancer Research, National Institutes
of Health [HHSN261200800001E]; Intramural Research Program of NIH,
National Laboratory for Cancer Research, Center for Cancer Research;
Korea Institute of Ocean Science Technology [PE98816]
FX We thank professors Apurba Dutta, University of Kansas, and Anders
Broberg, Swedish University of Agricultural Sciences, for synthetic
samples of (2S,3R)- and (2R,3S)-3-OH-aspartic acid, and threo- and
erythro-3-OH-glutamic acid, respectively. We thank the late Prof. Luigi
Minale for a sample of callipeltin A, Catherine Hixson (SAIC) for the
hydrolysis of 1 and 2, and S. Tarasov and M. Dyba, Biophysics Resource,
Structural Biophysics Laboratory for mass spectral analysis. This
project was funded in part with federal funds from the Frederick
National Laboratory for Cancer Research, National Institutes of Health
(contract HHSN261200800001E). This research was supported in part by the
Intramural Research Program of NIH, National Laboratory for Cancer
Research, Center for Cancer Research. The content of this publication
does not necessarily reflect the views or policies of the Department of
Health and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government.
This research was supported in part by the Korea Institute of Ocean
Science & Technology (Grant PE98816 to H.J.S.).
NR 18
TC 2
Z9 2
U1 2
U2 17
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0040-4039
J9 TETRAHEDRON LETT
JI Tetrahedron Lett.
PD JUL 8
PY 2015
VL 56
IS 28
BP 4215
EP 4219
DI 10.1016/j.tetlet.2015.05.058
PG 5
WC Chemistry, Organic
SC Chemistry
GA CL2EU
UT WOS:000356757200016
PM 26139946
ER
PT J
AU Sali, A
Berman, HM
Schwede, T
Trewhella, J
Kleywegt, G
Burley, SK
Markley, J
Nakamura, H
Adams, P
Bonvin, AMJJ
Chiu, W
Dal Peraro, M
Di Maio, F
Ferrin, TE
Grunewald, K
Gutmanas, A
Henderson, R
Hummer, G
Iwasaki, K
Johnson, G
Lawson, CL
Meiler, J
Marti-Renom, MA
Montelione, GT
Nilges, M
Nussinov, R
Patwardhan, A
Rappsilber, J
Read, RJ
Saibil, H
Schroder, GF
Schwieters, CD
Seidel, CAM
Svergun, D
Topf, M
Ulrich, EL
Velankar, S
Westbrook, JD
AF Sali, Andrej
Berman, Helen M.
Schwede, Torsten
Trewhella, Jill
Kleywegt, Gerard
Burley, Stephen K.
Markley, John
Nakamura, Haruki
Adams, Paul
Bonvin, Alexandre M. J. J.
Chiu, Wah
Dal Peraro, Matteo
Di Maio, Frank
Ferrin, Thomas E.
Gruenewald, Kay
Gutmanas, Aleksandras
Henderson, Richard
Hummer, Gerhard
Iwasaki, Kenji
Johnson, Graham
Lawson, Catherine L.
Meiler, Jens
Marti-Renom, Marc A.
Montelione, Gaetano T.
Nilges, Michael
Nussinov, Ruth
Patwardhan, Ardan
Rappsilber, Juri
Read, Randy J.
Saibil, Helen
Schroeder, Gunnar F.
Schwieters, Charles D.
Seidel, Claus A. M.
Svergun, Dmitri
Topf, Maya
Ulrich, Eldon L.
Velankar, Sameer
Westbrook, John D.
TI Outcome of the First wwPDB Hybrid/Integrative Methods Task Force
Workshop
SO STRUCTURE
LA English
DT News Item
ID ANGLE SCATTERING DATA; PROTEIN DATA-BANK; X-RAY-SCATTERING;
MASS-SPECTROMETRY; BINDING-PROTEIN; CROSS-LINKING; ELECTRON-MICROSCOPY;
STRUCTURAL BIOLOGY; NMR-SPECTROSCOPY; NUCLEIC-ACID
AB Structures of biomolecular systems are increasingly computed by integrative modeling that relies on varied types of experimental data and theoretical information. We describe here the proceedings and conclusions from the first wwPDB Hybrid/Integrative Methods Task Force Workshop held at the European Bioinformatics Institute in Hinxton, UK, on October 6 and 7, 2014. At the workshop, experts in various experimental fields of structural biology, experts in integrative modeling and visualization, and experts in data archiving addressed a series of questions central to the future of structural biology. How should integrative models be represented? How should the data and integrative models be validated? What data should be archived? How should the data and models be archived? What information should accompany the publication of integrative models?
C1 [Sali, Andrej] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, Dept Pharmaceut Chem, Calif Inst Quantitat Biosci, San Francisco, CA 94158 USA.
[Berman, Helen M.; Burley, Stephen K.; Lawson, Catherine L.; Westbrook, John D.] Rutgers State Univ, Ctr Integrat Prote Res, Res Collaboratory Struct Bioinformat Prot Data Ba, Piscataway, NJ 08854 USA.
[Schwede, Torsten] Univ Basel, Swiss Inst Bioinformat Biozentrum, CH-4056 Basel, Switzerland.
[Trewhella, Jill] Univ Sydney, Sch Mol Biosci, Sydney, NSW 2006, Australia.
[Kleywegt, Gerard; Gutmanas, Aleksandras; Patwardhan, Ardan; Velankar, Sameer] European Bioinformat Inst, Protein Data Bank Europe, European Mol Biol Lab, Cambridge CB10 1SD, England.
[Burley, Stephen K.] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA.
[Burley, Stephen K.] Univ Calif San Diego, San Diego Supercomp Ctr, La Jolla, CA 92093 USA.
[Markley, John; Ulrich, Eldon L.] Univ Wisconsin, Dept Biochem, BioMagResBank, Madison, WI 53706 USA.
[Nakamura, Haruki] Osaka Univ, Inst Prot Res, Protein Data Bank Japan, Suita, Osaka 5650871, Japan.
[Adams, Paul] Lawrence Berkeley Natl Lab, Phys Biosci Div, Berkeley, CA 94720 USA.
[Adams, Paul] Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA.
[Bonvin, Alexandre M. J. J.] Univ Utrecht, Fac Sci Chem, Bijvoet Ctr Biomol Res, NL-3584 CH Utrecht, Netherlands.
[Chiu, Wah] Baylor Coll Med, Natl Ctr Macromol Imaging, Houston, TX 77030 USA.
[Dal Peraro, Matteo] Ecole Polytech Fed Lausanne, Sch Life Sci, Inst Bioengn, CH-1015 Lausanne, Switzerland.
[Dal Peraro, Matteo] Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.
[Di Maio, Frank] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
[Ferrin, Thomas E.] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94158 USA.
[Ferrin, Thomas E.; Johnson, Graham] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, Calif Inst Quantitat Biosci, San Francisco, CA 94158 USA.
[Gruenewald, Kay] Univ Oxford, Wellcome Trust Ctr Human Genet, Div Struct Biol, Oxford OX3 7BN, England.
[Henderson, Richard] MRC Lab Mol Biol, Cambridge CB2 0QH, England.
[Hummer, Gerhard] Max Planck Inst Biophys, Dept Theoret Biophys, D-60438 Frankfurt, Germany.
[Iwasaki, Kenji] Osaka Univ, Inst Prot Res, Suita, Osaka 5650871, Japan.
[Meiler, Jens] Vanderbilt Univ, Struct Biol Ctr, Dept Chem, Nashville, TN 37235 USA.
[Marti-Renom, Marc A.] Ctr Genom Regulat, Genome Biol Grp, CNAG, Gene Regulat Stem Cells & Canc Program, Barcelona 08028, Spain.
[Marti-Renom, Marc A.] ICREA, Barcelona 08028, Spain.
[Montelione, Gaetano T.] Rutgers State Univ, Ctr Adv Biotechnol & Med, Dept Mol Biol & Biochem, Piscataway, NJ 08854 USA.
[Montelione, Gaetano T.] Rutgers State Univ, Robert Wood Johnson Med Sch, Dept Biochem, Piscataway, NJ 08854 USA.
[Nilges, Michael] Inst Pasteur, Unite Bioinformat Struct, Dept Biol Struct & Chim, F-75015 Paris, France.
[Nilges, Michael] Ctr Natl Rech Sci, Unite Mixte Rech 3258, F-75015 Paris, France.
[Nussinov, Ruth] NCI, Canc & Inflammat Program, Leidos Biomed Res Inc, Frederick Natl Lab, Frederick, MD 21702 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel.
[Rappsilber, Juri] Univ Edinburgh, Inst Cell Biol, Wellcome Trust Ctr Cell Biol, Edinburgh EH9 3BF, Midlothian, Scotland.
[Rappsilber, Juri] Tech Univ Berlin, Inst Biotechnol, Dept Bioanalyt, D-13355 Berlin, Germany.
[Read, Randy J.] Univ Cambridge, Dept Haematol, Cambridge Inst Med Res, Cambridge CB2 0XY, England.
[Saibil, Helen; Topf, Maya] Birkbeck Coll, Dept Biol Sci, Inst Struct & Mol Biol, London WC1E 7HX, England.
[Schroeder, Gunnar F.] Forschungszentrum Julich, Inst Complex Syst ICS 6, D-52425 Julich, Germany.
[Schroeder, Gunnar F.] Univ Dusseldorf, Phys Dept, D-40225 Dusseldorf, Germany.
[Schwieters, Charles D.] NIH, Ctr Informat Technol, Div Computat Biosci, Bethesda, MD 20892 USA.
[Seidel, Claus A. M.] Univ Dusseldorf, Chair Mol Phys Chem, D-40225 Dusseldorf, Germany.
[Svergun, Dmitri] European Mol Biol Lab, Hamburg Unit, D-22607 Hamburg, Germany.
RP Sali, A (reprint author), Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, Dept Pharmaceut Chem, Calif Inst Quantitat Biosci, Byers Hall Room 503B,1700 4th St, San Francisco, CA 94158 USA.
EM sali@salilab.org
RI Bonvin, Alexandre/A-5420-2009; Read, Randy/L-1418-2013; Schroder,
Gunnar/H-5261-2013; Hummer, Gerhard/A-2546-2013; Nilges,
Michael/E-4803-2011; Seidel, Claus/A-3682-2012;
OI Kleywegt, Gerard J./0000-0002-4670-0331; Patwardhan,
Ardan/0000-0001-7663-9028; Velankar, Sameer/0000-0002-8439-5964;
Grunewald, Kay/0000-0002-4788-2691; Rappsilber,
Juri/0000-0001-5999-1310; Bonvin, Alexandre/0000-0001-7369-1322;
Gutmanas, Aleksandras/0000-0001-6311-0176; Read,
Randy/0000-0001-8273-0047; Schroder, Gunnar/0000-0003-1803-5431; Hummer,
Gerhard/0000-0001-7768-746X; Nilges, Michael/0000-0002-1451-8092;
Seidel, Claus/0000-0002-5171-149X; Marti-Renom, Marc
A./0000-0002-0151-4279; Meiler, Jens/0000-0001-8945-193X
FU Wellcome Trust [088944]; NSF DBI [1338415]; JST-NBDC; NLM [P41 LM05799];
NIH [GM079429]; wwPDB outreach activities
FX The workshop was supported by funding to PDBe by Wellcome Trust 088944;
RCSB PDB by NSF DBI 1338415; PDBj by JST-NBDC; BMRB by NLM P41 LM05799;
EMDataBank by NIH GM079429; and tax-deductible donations made to the
wwPDB Foundation in support of wwPDB outreach activities.
NR 73
TC 26
Z9 26
U1 5
U2 20
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0969-2126
EI 1878-4186
J9 STRUCTURE
JI Structure
PD JUL 7
PY 2015
VL 23
IS 7
BP 1156
EP 1167
DI 10.1016/j.str.2015.05.013
PG 12
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA CQ0UG
UT WOS:000360312200004
PM 26095030
ER
PT J
AU Muratcioglu, S
Chavan, TS
Freed, BC
Jang, H
Khavrutskii, L
Freed, RN
Dyba, MA
Stefanisko, K
Tarasov, SG
Gursoy, A
Keskin, O
Tarasova, NI
Gaponenko, V
Nussinov, R
AF Muratcioglu, Serena
Chavan, Tanmay S.
Freed, Benjamin C.
Jang, Hyunbum
Khavrutskii, Lyuba
Freed, R. Natasha
Dyba, Marzena A.
Stefanisko, Karen
Tarasov, Sergey G.
Gursoy, Attila
Keskin, Ozlem
Tarasova, Nadya I.
Gaponenko, Vadim
Nussinov, Ruth
TI GTP-Dependent K-Ras Dimerization
SO STRUCTURE
LA English
DT Article
ID PROTEIN-PROTEIN INTERACTIONS; PLASMA-MEMBRANE; FORMS DIMERS; H-RAS;
INTERFACE; CANCER; ACTIVATION; DOMAIN; EVOLUTIONARY; SIMILARITIES
AB Ras proteins recruit and activate effectors, including Raf, that transmit receptor-initiated signals. Monomeric Ras can bind Raf; however, activation of Raf requires its dimerization. It has been suspected that dimeric Ras may promote dimerization and activation of Raf. Here, we show that the GTP-bound catalytic domain of K-Ras4B, a highly oncogenic splice variant of the K-Ras isoform, forms stable homodimers. We observe two major dimer interfaces. The first, highly populated beta-sheet dimer interface is at the Switch I and effector binding regions, overlapping the binding surfaces of Raf, PI3K, RalGDS, and additional effectors. This interface has to be inhibitory to such effectors. The second, helical interface also overlaps the binding sites of some effectors. This interface may promote activation of Raf. Our data reveal how Ras self-association can regulate effector binding and activity, and suggest that disruption of the helical dimer interface by drugs may abate Raf signaling in cancer.
C1 [Muratcioglu, Serena; Keskin, Ozlem] Koc Univ, Dept Chem & Biol Engn, TR-34450 Sariyer, Turkey.
[Chavan, Tanmay S.] Univ Illinois, Dept Med Chem, Chicago, IL 60607 USA.
[Chavan, Tanmay S.; Gaponenko, Vadim] Univ Illinois, Dept Biochem & Mol Genet, Chicago, IL 60607 USA.
[Freed, Benjamin C.; Jang, Hyunbum; Khavrutskii, Lyuba; Freed, R. Natasha; Stefanisko, Karen; Tarasova, Nadya I.; Nussinov, Ruth] NCI, Canc & Inflammat Program, Frederick, MD 21702 USA.
[Jang, Hyunbum; Khavrutskii, Lyuba; Dyba, Marzena A.; Nussinov, Ruth] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Basic Sci Program, Frederick, MD 21702 USA.
[Dyba, Marzena A.; Tarasov, Sergey G.] NCI, Struct Biophys Lab, Frederick, MD 21702 USA.
[Gursoy, Attila] Koc Univ, Dept Comp Engn, TR-34450 Sariyer, Turkey.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel.
RP Gaponenko, V (reprint author), Univ Illinois, Dept Biochem & Mol Genet, Chicago, IL 60607 USA.
EM vadimg@uic.edu; nussinor@helix.nih.gov
RI Gursoy, Attila/E-9565-2015
OI Gursoy, Attila/0000-0002-2297-2113
FU American Cancer Society [RGS-09-057-01-GMC]; National Cancer Institute
[R01 CA135341]; Frederick National Laboratory for Cancer Research, NIH
[HHSN261200800001E]; Intramural Research Program of NIH, Frederick
National Lab, Center for Cancer Research
FX We thank Finn Mannerings for her help with protein expression and
purification of K-Ras protein. We gratefully acknowledge the generous
support from the American Cancer Society Grant RGS-09-057-01-GMC and the
National Cancer Institute Grant R01 CA135341 to V.G. This project has
been funded in whole or in part with Federal funds from the Frederick
National Laboratory for Cancer Research, NIH, under contract
HHSN261200800001E. This research was supported (in part) by the
Intramural Research Program of NIH, Frederick National Lab, Center for
Cancer Research. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products or
organizations imply endorsement by the US Government. Computations have
been performed at the high-performance center, Koc University.
NR 51
TC 36
Z9 36
U1 0
U2 14
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0969-2126
EI 1878-4186
J9 STRUCTURE
JI Structure
PD JUL 7
PY 2015
VL 23
IS 7
BP 1325
EP 1335
DI 10.1016/j.str.2015.04.019
PG 11
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA CQ0UG
UT WOS:000360312200019
PM 26051715
ER
PT J
AU Barragan, S
Rueda, C
Fernandez, MA
Peddada, SD
AF Barragan, Sandra
Rueda, Cristina
Fernandez, Miguel A.
Peddada, Shyamal D.
TI Determination of Temporal Order among the Components of an Oscillatory
System
SO PLOS ONE
LA English
DT Article
ID CYCLE-REGULATED GENES; CELL-CYCLE; FISSION YEAST; CIRCADIAN CLOCK;
EXPRESSION; IDENTIFICATION; EUKARYOTES; BRAIN; PREDICTION; DATABASE
AB Oscillatory systems in biology are tightly regulated process where the individual components (e.g. genes) express in an orderly manner by virtue of their functions. The temporal order among the components of an oscillatory system may potentially be disrupted for various reasons (e.g. environmental factors). As a result some components of the system may go out of order or even cease to participate in the oscillatory process. In this article, we develop a novel framework to evaluate whether the temporal order is unchanged in different populations (or experimental conditions). We also develop methodology to estimate the order among the components with a suitable notion of "confidence." Using publicly available data on S. pombe, S. cerevisiae and Homo sapiens we discover that the temporal order among the genes cdc18; mik1; hhf1; hta2; fkh2 and klp5 is evolutionarily conserved from yeast to humans.
C1 [Barragan, Sandra; Rueda, Cristina; Fernandez, Miguel A.] Univ Valladolid, Dept Estadist & Invest Operat, Valladolid, Spain.
[Peddada, Shyamal D.] NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA.
RP Peddada, SD (reprint author), NIEHS, Biostat Branch, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM peddada@niehs.nih.gov
RI Fernandez, Miguel/I-2874-2015
OI Fernandez, Miguel/0000-0002-1272-8950
FU Spanish Ministerio de Ciencia e Innovacion [MTM2012-37129]; Junta de
Castilla y Leon, Consejeria de Educacion; European Social Fund within
the Programa Operativo Castilla y Leon; Intramural Research Program of
the National Institute of Environmental Health Sciences [Z01
ES101744-04]
FX The research of SB, MAF and CR was funded by the Spanish Ministerio de
Ciencia e Innovacion grant (MTM2012-37129). SB was also funded by the
Junta de Castilla y Leon, Consejeria de Educacion and the European
Social Fund within the Programa Operativo Castilla y Leon 2007-2013. The
research of SDP was supported by the Intramural Research Program of the
National Institute of Environmental Health Sciences (Z01 ES101744-04).
NR 54
TC 0
Z9 0
U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 7
PY 2015
VL 10
IS 7
AR e0124842
DI 10.1371/journal.pone.0124842
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN1EC
UT WOS:000358158900002
PM 26151635
ER
PT J
AU Hanson, SM
Sansom, MSP
Becker, EBE
AF Hanson, Sonya M.
Sansom, Mark S. P.
Becker, Esther B. E.
TI Modeling Suggests TRPC3 Hydrogen Bonding and Not Phosphorylation
Contributes to the Ataxia Phenotype of the Moonwalker Mouse
SO BIOCHEMISTRY
LA English
DT Article
ID PROTEIN-KINASE-C; OF-FUNCTION MUTATIONS; CEREBELLAR-ATAXIA; CHANNELS;
PREDICTION; MICE; CALCIUM; CALCINEURIN; DYSFUNCTION; SIMULATIONS
AB A gain-of-function mutation (T635A) in the transient receptor potential (TRP) channel TRPC3 results in abnormal channel gating and causes cerebellar ataxia in the dominant Moonwalker (Mwk) mouse mutant. However, the underlying molecular and structural mechanisms are unclear. Here, we used a combined approach of computational modeling and functional characterization of proposed TRPC3 mutants. Our findings support a mechanism by which the hydrogen bonding capability of threonine 635 plays a significant role in maintaining a stable, closed state channel. This capability is lost in the Mwk mutant, suggesting a structural basis for the disease-causing phenotype in the Mwk mouse.
C1 [Hanson, Sonya M.] NINDS, Mol Physiol & Biophys Unit, NIH, Bethesda, MD 20892 USA.
[Hanson, Sonya M.; Sansom, Mark S. P.] Univ Oxford, Dept Biochem, Oxford OX1 3QU, England.
[Becker, Esther B. E.] Univ Oxford, Dept Physiol Anat & Genet, MRC Funct Genom Unit, Oxford OX1 3PT, England.
RP Becker, EBE (reprint author), Univ Oxford, Dept Physiol Anat & Genet, MRC Funct Genom Unit, Sherrington Rd, Oxford OX1 3PT, England.
EM esther.becker@dpag.ox.ac.uk
FU Royal Society; NIH-Oxford Scholars Program; Wellcome Trust
FX E.B.E.B. is the recipient of a Royal Society Research Fellowship. S.M.H.
was supported by the NIH-Oxford Scholars Program during much of this
work. Research in M.S.P.S.'s group is supported by The Wellcome Trust.
NR 41
TC 0
Z9 0
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD JUL 7
PY 2015
VL 54
IS 26
BP 4033
EP 4041
DI 10.1021/acs.biochem.5b00235
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CM6ZG
UT WOS:000357839600003
PM 26112884
ER
PT J
AU Neufer, PD
Bamman, MM
Muoio, DM
Bouchard, C
Cooper, DM
Goodpaster, BH
Booth, FW
Kohrt, WM
Gerszten, RE
Mattson, MP
Hepple, RT
Kraus, WE
Reid, MB
Bodine, SC
Jakicic, JM
Fleg, JL
Williams, JP
Joseph, L
Evans, M
Maruvada, P
Rodgers, M
Roary, M
Boyce, AT
Drugan, JK
Koenig, JI
Ingraham, RH
Krotoski, D
Garcia-Cazarin, M
McGowan, JA
Laughlin, MR
AF Neufer, P. Darrell
Bamman, Marcas M.
Muoio, Deborah M.
Bouchard, Claude
Cooper, Dan M.
Goodpaster, Bret H.
Booth, Frank W.
Kohrt, Wendy M.
Gerszten, Robert E.
Mattson, Mark P.
Hepple, Russell T.
Kraus, William E.
Reid, Michael B.
Bodine, Sue C.
Jakicic, John M.
Fleg, Jerome L.
Williams, John P.
Joseph, Lyndon
Evans, Mary
Maruvada, Padma
Rodgers, Mary
Roary, Mary
Boyce, Amanda T.
Drugan, Jonelle K.
Koenig, James I.
Ingraham, Richard H.
Krotoski, Danuta
Garcia-Cazarin, Mary
McGowan, Joan A.
Laughlin, Maren R.
TI Understanding the Cellular and Molecular Mechanisms of Physical
Activity-Induced Health Benefits
SO CELL METABOLISM
LA English
DT Review
ID HUMAN SKELETAL-MUSCLE; MESSENGER-RNA EXPRESSION; MITOCHONDRIAL
BIOGENESIS; CARDIOVASCULAR-DISEASE; RESISTANCE EXERCISE; METABOLIC
SYNDROME; MODERATE EXERCISE; GENE-EXPRESSION; ADIPOSE-TISSUE;
CLINICAL-TRIAL
AB The beneficial effects of physical activity (PA) are well documented, yet the mechanisms by which PA prevents disease and improves health outcomes are poorly understood. To identify major gaps in knowledge and potential strategies for catalyzing progress in the field, the NIH convened a workshop in late October 2014 entitled "Understanding the Cellular and Molecular Mechanisms of Physical Activity-Induced Health Benefits.'' Presentations and discussions emphasized the challenges imposed by the integrative and intermittent nature of PA, the tremendous discovery potential of applying "-omics'' technologies to understand interorgan crosstalk and biological networking systems during PA, and the need to establish an infrastructure of clinical trial sites with sufficient expertise to incorporate mechanistic outcome measures into adequately sized human PA trials. Identification of the mechanisms that underlie the link between PA and improved health holds extraordinary promise for discovery of novel therapeutic targets and development of personalized exercise medicine.
C1 [Neufer, P. Darrell] E Carolina Univ, Brody Sch Med, Dept Physiol, East Carolina Diabet & Obes Inst, Greenville, NC 27834 USA.
[Neufer, P. Darrell] E Carolina Univ, Brody Sch Med, Dept Kinesiol, East Carolina Diabet & Obes Inst, Greenville, NC 27834 USA.
[Bamman, Marcas M.] Univ Alabama Birmingham, UAB Ctr Exercise Med, Birmingham, AL 35294 USA.
[Bamman, Marcas M.] Univ Alabama Birmingham, Dept Cell Dev & Integrat Biol, Birmingham, AL 35294 USA.
[Muoio, Deborah M.; Kraus, William E.] Duke Univ, Sch Med, Duke Mol Physiol, Durham, NC 27701 USA.
[Bouchard, Claude] Louisiana State Univ, Pennington Biomed Res Ctr, Human Genom Lab, Baton Rouge, LA 70808 USA.
[Cooper, Dan M.] Univ Calif Irvine, UC Irvine Inst Clin & Translat Sci, Irvine, CA 92697 USA.
[Cooper, Dan M.] Univ Calif Irvine, Dept Pediat, Irvine, CA 92697 USA.
[Goodpaster, Bret H.] Florida Hosp, Sanford Burnham Med Res Inst, Translat Res Inst Metab & Diabet, Orlando, FL 32804 USA.
[Booth, Frank W.] Univ Missouri, Dept Biomed Sci, Columbia, MO 65211 USA.
[Booth, Frank W.] Univ Missouri, Dept Med Pharmacol & Physiol, Columbia, MO 65211 USA.
[Booth, Frank W.] Univ Missouri, Dept Nutr & Exercise Physiol, Columbia, MO 65211 USA.
[Kohrt, Wendy M.] Univ Colorado, Sch Med, Div Geriatr Med, Aurora, CO 80045 USA.
[Gerszten, Robert E.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Gerszten, Robert E.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Gerszten, Robert E.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Mattson, Mark P.] NIA, Lab Neurosci, Intramural Res Program, Baltimore, MD 21224 USA.
[Hepple, Russell T.] McGill Univ, Ctr Hlth, Dept Kinesiol, Montreal, PQ H2W 1S4, Canada.
[Reid, Michael B.] Univ Florida, Dept Appl Physiol & Kinesiol, Gainesville, FL 32611 USA.
[Bodine, Sue C.] Univ Calif Davis, Dept Neurobiol Physiol & Behav, Davis, CA 95616 USA.
[Jakicic, John M.] Univ Pittsburgh, Dept Hlth & Phys Act, Phys Act & Weight Management Res Ctr, Pittsburgh, PA 15261 USA.
[Fleg, Jerome L.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Williams, John P.; Joseph, Lyndon] NIA, NIH, Bethesda, MD 20892 USA.
[Evans, Mary; Maruvada, Padma; Laughlin, Maren R.] NIDDK, NIH, Bethesda, MD 20892 USA.
[Rodgers, Mary] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA.
[Roary, Mary] NINR, NIH, Bethesda, MD 20892 USA.
[Boyce, Amanda T.; Drugan, Jonelle K.; McGowan, Joan A.] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Koenig, James I.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA.
[Ingraham, Richard H.] NIH, Ctr Sci Review, Bethesda, MD 20892 USA.
[Krotoski, Danuta] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
[Garcia-Cazarin, Mary] NIH, Off Dis Prevent, Bethesda, MD 20892 USA.
RP Neufer, PD (reprint author), E Carolina Univ, Brody Sch Med, Dept Physiol, East Carolina Diabet & Obes Inst, Greenville, NC 27834 USA.
EM neuferp@ecu.edu
RI Bouchard, Claude/A-7637-2009
FU NIH Common Fund
FX We gratefully acknowledge financial support from the NIH Common Fund and
the following individuals that participated in webinars and conference
calls leading up to the workshop: Shannon Bailey, Robert Balaban,
Charles Burant, Richard Casaburi, Shulin Cheng, Charlene Chu, Roger
Fielding, Monika Fleshner, Jacob Friedman, Paige Geiger, John Holloszy,
Lee Jones, Gabrielle Kardon, Christiaan Leeuwenburgh, Gregory Lewis,
Wendy Lynch, Paul MacLean, Sreekumaran Nair, Robert O'Doherty, Charlotte
Peterson, Orian Shirihai, Kathleen Sluka, Bruce Spiegelman, Russel
Swerdlow, John Thyfault, James Tidball, Rick Vega, Eric Verdin, Douglas
Wallace, Zhen Yan, Juleen Zierath, and Michael Zigmond. We also
gratefully acknowledge additional members of the NIH Working Group: D.
Lee Alekel, Catherine Alfano, Josephine E. Boyington, Rosalind A.
Breslow, Carole Christian, Wilson Compton, Lawton Cooper, Augusto Diana,
Luigi Ferrucci, Katrina Gwinn, Lynda Hardy, Tamara B. Harris, Lynne
Haverkos, Mary Kautz, Partap Khalsa, Delvin Knight, Frank Perna, Barry
Portnoy, Xenia Tigno, Richard Troiano, Elizabeth Wilder, Lois Winsky,
Pamela Wolters, and Steve Zullo. The views expressed are those of the
authors and do not necessarily reflect those of the NIH or the
Department of Health and Human Services of the United States.
NR 57
TC 39
Z9 39
U1 3
U2 37
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1550-4131
EI 1932-7420
J9 CELL METAB
JI Cell Metab.
PD JUL 7
PY 2015
VL 22
IS 1
BP 4
EP 11
DI 10.1016/j.cmet.2015.05.011
PG 8
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA CM4LU
UT WOS:000357656900003
PM 26073496
ER
PT J
AU Rickman, KA
Lach, FP
Abhyankar, A
Donovan, FX
Sanborn, EM
Kennedy, JA
Sougnez, C
Gabriel, SB
Elemento, O
Chandrasekharappa, SC
Schindler, D
Auerbach, AD
Smogorzewska, A
AF Rickman, Kimberly A.
Lach, Francis P.
Abhyankar, Avinash
Donovan, Frank X.
Sanborn, Erica M.
Kennedy, Jennifer A.
Sougnez, Carrie
Gabriel, Stacey B.
Elemento, Olivier
Chandrasekharappa, Settara C.
Schindler, Detlev
Auerbach, Arleen D.
Smogorzewska, Agata
TI Deficiency of UBE2T, the E2 Ubiquitin Ligase Necessary for FANCD2 and
FANCI Ubiquitination, Causes FA-T Subtype of Fanconi Anemia
SO CELL REPORTS
LA English
DT Article
ID CROSS-LINK REPAIR; SOMATIC MOSAICISM; DNA-REPAIR; PATHWAY; GENE;
MONOUBIQUITINATION; MUTATIONS; DIAGNOSIS; ALDEHYDES; PROTEINS
AB Fanconi anemia (FA) is a rare bone marrow failure and cancer predisposition syndrome resulting from pathogenic mutations in genes encoding proteins participating in the repair of DNA interstrand crosslinks (ICLs). Mutations in 17 genes (FANCA-FANCS) have been identified in FA patients, defining 17 complementation groups. Here, we describe an individual presenting with typical FA features who is deficient for the ubiquitin-conjugating enzyme (E2), UBE2T. UBE2T is known to interact with FANCL, the E3 ubiquitin-ligase component of the multiprotein FA core complex, and is necessary for the monoubiquitination of FANCD2 and FANCI. Proband fibroblasts do not display FANCD2 and FANCI monoubiquitination, do not form FANCD2 foci following treatment with mitomycin C, and are hypersensitive to crosslinking agents. These cellular defects are complemented by expression of wild-type UBE2T, demonstrating that deficiency of the protein UBE2T can lead to Fanconi anemia. UBE2T gene gains an alias of FANCT.
C1 [Rickman, Kimberly A.; Lach, Francis P.; Sanborn, Erica M.; Kennedy, Jennifer A.; Smogorzewska, Agata] Rockefeller Univ, Lab Genome Maintenance, New York, NY 10065 USA.
[Abhyankar, Avinash] New York Genome Ctr, New York, NY 10013 USA.
[Donovan, Frank X.; Chandrasekharappa, Settara C.] NHGRI, Canc Genet & Comparat Genom Branch, NIH, Bethesda, MD 20892 USA.
[Sougnez, Carrie; Gabriel, Stacey B.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
[Elemento, Olivier] Weill Cornell Med Coll, Inst Computat Biomed, Dept Physiol & Biophys, New York, NY 10021 USA.
[Schindler, Detlev] Univ Wurzburg, Inst Human Genet, Biozentrum, D-97074 Wurzburg, Germany.
[Auerbach, Arleen D.] Rockefeller Univ, Human Genet & Hematol, New York, NY 10065 USA.
RP Smogorzewska, A (reprint author), Rockefeller Univ, Lab Genome Maintenance, New York, NY 10065 USA.
EM asmogorzewska@rockefeller.edu
OI Auerbach, Arleen/0000-0002-6911-8379
FU Starr Cancer Consortium; Burroughs Welcome Fund; Doris Duke Charitable
Foundation; Vilcek Foundation; Rockefeller University; NIH [RO1
HL120922]; National Center for Advancing Translational Sciences, NIH [8
UL1 TR000043]; National Human Genome Research Institute, NIH; National
Institute of General Medical Sciences of the NIH [T32GM007739]
FX We wish to thank the subject and family for their participation in this
study. We would like to acknowledge Richard Harris and Stella Davies for
providing clinical data and patient care. The work was supported by the
Starr Cancer Consortium grant (to A.S. and S.B.G.), the Burroughs
Welcome Fund Career Award for Medical Scientists (to A.S.), the Doris
Duke Charitable Foundation Clinical Scientist Development Award (to
A.S.), and the Vilcek Foundation (to A.D.A.). The International Fanconi
Anemia Registry is supported by the Rockefeller University, NIH RO1
HL120922 (to A.S.), and grant no. 8 UL1 TR000043 from the National
Center for Advancing Translational Sciences, NIH Clinical and
Translational Science Award program. F.X.D. and S.C.C. acknowledge the
support from the Intramural Research Program of the National Human
Genome Research Institute, NIH. K.A.R. was supported by a Medical
Scientist Training Program grant from the National Institute of General
Medical Sciences of the NIH under award number T32GM007739 to the Weill
Cornell/Rockefeller/Sloan-Kettering Tri-Institutional MD-PhD Program.
The content of this study is solely the responsibility of the authors
and does not necessarily represent the official views of the NIH.
NR 37
TC 32
Z9 32
U1 8
U2 16
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2211-1247
J9 CELL REP
JI Cell Reports
PD JUL 7
PY 2015
VL 12
IS 1
BP 35
EP 41
DI 10.1016/j.celrep.2015.06.014
PG 7
WC Cell Biology
SC Cell Biology
GA CM4RV
UT WOS:000357673300005
PM 26119737
ER
PT J
AU Kim, S
Han, LY
Yu, B
Hahnke, VD
Bolton, EE
Bryant, SH
AF Kim, Sunghwan
Han, Lianyi
Yu, Bo
Haehnke, Volker D.
Bolton, Evan E.
Bryant, Stephen H.
TI PubChem structure-activity relationship (SAR) clusters
SO JOURNAL OF CHEMINFORMATICS
LA English
DT Article
DE PubChem; PubChem3D; Structure-activity relationship (SAR); Cluster
analysis; Molecular similarity; BioSystems; MeSH
ID ARYL-HYDROCARBON RECEPTOR; THROUGHPUT SCREENING DATA; CARBONIC-ANHYDRASE
INHIBITORS; SMALL MOLECULES; SIMILARITY COEFFICIENTS;
SIGNAL-TRANSDUCTION; 3-D SIMILARITY; DATABASE; SHAPE; PATHWAYS
AB Background: Developing structure-activity relationships (SARs) of molecules is an important approach in facilitating hit exploration in the early stage of drug discovery. Although information on millions of compounds and their bioactivities is freely available to the public, it is very challenging to infer a meaningful and novel SAR from that information.
Results: Research discussed in the present paper employed a bioactivity-centered clustering approach to group 843,845 non-inactive compounds stored in PubChem according to both structural similarity and bioactivity similarity, with the aim of mining bioactivity data in PubChem for useful SAR information. The compounds were clustered in three bioactivity similarity contexts: (1) non-inactive in a given bioassay, (2) non-inactive against a given protein, and (3) non-inactive against proteins involved in a given pathway. In each context, these small molecules were clustered according to their two-dimensional (2-D) and three-dimensional (3-D) structural similarities. The resulting 18 million clusters, named "PubChem SAR clusters", were delivered in such a way that each cluster contains a group of small molecules similar to each other in both structure and bioactivity.
Conclusions: The PubChem SAR clusters, pre-computed using publicly available bioactivity information, make it possible to quickly navigate and narrow down the compounds of interest. Each SAR cluster can be a useful resource in developing a meaningful SAR or enable one to design or expand compound libraries from the cluster. It can also help to predict the potential therapeutic effects and pharmacological actions of less-known compounds from those of well-known compounds (i. e., drugs) in the same cluster.
[GRAPHICS]
C1 [Kim, Sunghwan; Han, Lianyi; Yu, Bo; Haehnke, Volker D.; Bolton, Evan E.; Bryant, Stephen H.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Dept Hlth & Human Serv, Bethesda, MD 20894 USA.
RP Bolton, EE (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Dept Hlth & Human Serv, 8600 Rockville Pike, Bethesda, MD 20894 USA.
EM bolton@ncbi.nlm.nih.gov
RI Kim, Sunghwan/A-6738-2008
OI Kim, Sunghwan/0000-0001-9828-2074
FU Intramural Research Program of the National Library of Medicine,
National Institutes of Health, U.S. Department of Health and Human
Services
FX We thank John MacCuish, Norah MacCuish, and Mitch Chapman at Mesa
Analytics and Computing, Inc. for providing us with their clustering
software and insightful advice. We are also grateful to the NCBI Systems
staff, especially Ron Patterson, Charlie Cook, and Don Preuss, whose
efforts helped make the PubChem3D project possible. We also thank Cindy
Clark, NIH Library Editing Service, for reviewing the manuscript. This
research was supported by the Intramural Research Program of the
National Library of Medicine, National Institutes of Health, U.S.
Department of Health and Human Services.
NR 52
TC 3
Z9 3
U1 1
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1758-2946
J9 J CHEMINFORMATICS
JI J. Cheminformatics
PD JUL 7
PY 2015
VL 7
AR 33
DI 10.1186/s13321-015-0070-x
PG 22
WC Chemistry, Multidisciplinary; Computer Science, Information Systems;
Computer Science, Interdisciplinary Applications
SC Chemistry; Computer Science
GA CM3CH
UT WOS:000357558800001
PM 26150895
ER
PT J
AU Absinta, M
Vuolo, L
Rao, A
Nair, G
Sati, P
Cortese, ICM
Ohayon, J
Fenton, K
Reyes-Mantilla, MI
Maric, D
Calabresi, PA
Butman, JA
Pardo, CA
Reich, DS
AF Absinta, Martina
Vuolo, Luisa
Rao, Anuradha
Nair, Govind
Sati, Pascal
Cortese, Irene C. M.
Ohayon, Joan
Fenton, Kaylan
Reyes-Mantilla, Maria I.
Maric, Dragan
Calabresi, Peter A.
Butman, John A.
Pardo, Carlos A.
Reich, Daniel S.
TI Gadolinium-based MRI characterization of leptomeningeal inflammation in
multiple sclerosis
SO NEUROLOGY
LA English
DT Article
ID ATTENUATED INVERSION-RECOVERY; CORTICAL LESION DETECTION; B-CELL
FOLLICLES; MENINGEAL INFLAMMATION; MULTICENTER TRIAL; DISEASE;
RITUXIMAB; PATHOLOGY; ONSET; DEMYELINATION
AB Objective:
To determine the frequency and nature of leptomeningeal contrast enhancement in multiple sclerosis (MS) via in vivo 3-tesla postcontrast T2-weighted, fluid-attenuated inversion recovery (FLAIR) MRI and 7-tesla postmortem MRI-pathology correlation.
Methods:
Brain MRI, using the postcontrast T2-weighted, FLAIR technique, was prospectively collected in 299 MS cases and 37 age-matched neurologically healthy controls. Expert raters evaluated focal gadolinium enhancement in the leptomeningeal compartment. Two progressive MS cases came to autopsy after in vivo MRI characterization. Pathologic and immunohistochemical examination assessed the association of enhancement with leptomeningeal inflammation and adjacent cortical demyelination.
Results:
Focal contrast enhancement was detected in the leptomeningeal compartment in 74 of 299 MS cases (25%) vs 1 of 37 neurologically healthy controls (2.7%; p = 0.001). Enhancement was nearly twice as frequent (p = 0.009) in progressive MS (39/118 cases, 33%) as in relapsing-remitting MS (35/181, 19%). Enhancing foci generally remained stable throughout the evaluation period (up to 5.5 years). Pathology showed perivascular lymphocytic and mononuclear infiltration in the enhancing areas in association with flanking subpial cortical demyelination.
Conclusion:
Leptomeningeal contrast enhancement occurs frequently in MS and is a noninvasive, in vivo marker of inflammation and associated subpial demyelination. It might therefore enable testing of new treatments aimed at eliminating this inflammation and potentially arresting progressive MS.
C1 [Absinta, Martina; Vuolo, Luisa; Rao, Anuradha; Nair, Govind; Sati, Pascal; Reich, Daniel S.] NINDS, Translat Neuroradiol Unit, NIH, Bethesda, MD 20892 USA.
[Cortese, Irene C. M.; Ohayon, Joan; Fenton, Kaylan] NINDS, Neuroimmunol Clin, NIH, Bethesda, MD 20892 USA.
[Maric, Dragan] NINDS, Flow Cytometry Core Facil, NIH, Bethesda, MD 20892 USA.
[Absinta, Martina] Univ Vita Salute San Raffaele, San Raffaele Sci Inst, Inst Expt Neurol, Neuroimaging Res Unit Div Neurosci, Milan, Italy.
[Vuolo, Luisa] Univ Florence, Dept Neurol & Radiol, I-50121 Florence, Italy.
[Reyes-Mantilla, Maria I.; Calabresi, Peter A.; Pardo, Carlos A.] Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD USA.
[Butman, John A.; Reich, Daniel S.] NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA.
RP Reich, DS (reprint author), NINDS, Translat Neuroradiol Unit, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM daniel.reich@nih.gov
RI Reich, Daniel/E-5701-2010
OI Reich, Daniel/0000-0002-2628-4334
FU Intramural Research Program of the National Institute of Neurological
Disorders and Stroke
FX The Intramural Research Program of the National Institute of
Neurological Disorders and Stroke supported this study.
NR 35
TC 26
Z9 26
U1 0
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD JUL 7
PY 2015
VL 85
IS 1
BP 18
EP 28
DI 10.1212/WNL.0000000000001587
PG 11
WC Clinical Neurology
SC Neurosciences & Neurology
GA CM2AQ
UT WOS:000357482300005
PM 25888557
ER
PT J
AU Goetzl, EJ
Boxer, A
Schwartz, JB
Abner, EL
Petersen, RC
Miller, BL
Kapogiannis, D
AF Goetzl, Edward J.
Boxer, Adam
Schwartz, Janice B.
Abner, Erin L.
Petersen, Ronald C.
Miller, Bruce L.
Kapogiannis, Dimitrios
TI Altered lysosomal proteins in neural-derived plasma exosomes in
preclinical Alzheimer disease
SO NEUROLOGY
LA English
DT Article
ID CATHEPSIN-D; CEREBROSPINAL-FLUID; CLINICAL-TRIALS; ADAS-COG; HSP70;
BIOGENESIS; DIAGNOSIS; CRITERIA
AB Objective:
Diverse autolysosomal proteins were quantified in neurally derived blood exosomes from patients with Alzheimer disease (AD) and controls to investigate disordered neuronal autophagy.
Methods:
Blood exosomes obtained once from patients with AD (n = 26) or frontotemporal dementia (n = 16), other patients with AD (n = 20) both when cognitively normal and 1 to 10 years later when diagnosed, and case controls were enriched for neural sources by anti-human L1CAM antibody immunoabsorption. Extracted exosomal proteins were quantified by ELISAs and normalized with the CD81 exosomal marker.
Results:
Mean exosomal levels of cathepsin D, lysosome-associated membrane protein 1 (LAMP-1), and ubiquitinylated proteins were significantly higher and of heat-shock protein 70 significantly lower for AD than controls in cross-sectional studies (p <= 0.0005). Levels of cathepsin D, LAMP-1, and ubiquitinylated protein also were significantly higher for patients with AD than for patients with frontotemporal dementia (p <= 0.006). Step-wise discriminant modeling of the protein levels correctly classified 100% of patients with AD. Exosomal levels of all proteins were similarly significantly different from those of matched controls in 20 patients 1 to 10 years before and at diagnosis of AD (p <= 0.0003).
Conclusions:
Levels of autolysosomal proteins in neurally derived blood exosomes distinguish patients with AD from case controls and appear to reflect the pathology of AD up to 10 years before clinical onset. These preliminary results confirm in living patients with AD the early appearance of neuronal lysosomal dysfunction and suggest that these proteins may be useful biomarkers in large prospective studies.
C1 [Goetzl, Edward J.] UCSF Med Ctr, Dept Med, San Francisco, CA 94143 USA.
Jewish Home San Francisco, San Francisco, CA USA.
[Boxer, Adam; Miller, Bruce L.] UCSF Med Ctr, Dept Neurol, Memory & Aging Ctr, San Francisco, CA USA.
[Schwartz, Janice B.] UCSF, Dept Med, San Francisco, CA USA.
[Schwartz, Janice B.] UCSF, Dept Bioengn, San Francisco, CA USA.
[Abner, Erin L.] Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40506 USA.
[Petersen, Ronald C.] Mayo Clin, Dept Neurol, Rochester, MN USA.
[Kapogiannis, Dimitrios] NIA, Intramural Res Program, Baltimore, MD 21224 USA.
RP Goetzl, EJ (reprint author), UCSF Med Ctr, Dept Med, San Francisco, CA 94143 USA.
EM edward.goetzl@ucsf.edu
FU Intramural Research Program of the National Institute on Aging (NIA); UK
ADC [P30, AG028383]; NanoSomiX, Inc.
FX Intramural Research Program of the National Institute on Aging (NIA;
D.K.), UK ADC P30, AG028383 (E.L.A.), and an unrestricted grant for
method development from NanoSomiX, Inc. (E.J.G.).
NR 30
TC 32
Z9 33
U1 6
U2 32
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD JUL 7
PY 2015
VL 85
IS 1
BP 40
EP 47
DI 10.1212/WNL.0000000000001702
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA CM2AQ
UT WOS:000357482300007
PM 26062630
ER
PT J
AU Corbett, GT
Gonzalez, FJ
Pahan, K
AF Corbett, Grant T.
Gonzalez, Frank J.
Pahan, Kalipada
TI Activation of peroxisome proliferator-activated receptor alpha
stimulates ADAM10-mediated proteolysis of APP
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE PPARalpha; ADAM10; APP; Alzheimer's disease
ID AMYLOID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; PLAQUE-FORMATION;
SECRETASE ADAM10; TRANSGENIC MICE; RETINOIC ACID; BETA-PROTEIN; BRAIN;
NEURODEGENERATION; PLASTICITY
AB Amyloid precursor protein (APP) derivative beta-amyloid (A beta) plays an important role in the pathogenesis of Alzheimer's disease (AD). Sequential proteolysis of APP by beta-secretase and.-secretase generates A beta. Conversely, the alpha-secretase "a disintegrin and metalloproteinase" 10 (ADAM10) cleaves APP within the eventual A beta sequence and precludes A beta generation. Therefore, up-regulation of ADAM10 represents a plausible therapeutic strategy to combat overproduction of neurotoxic A beta. Peroxisome proliferator-activated receptor alpha (PPAR alpha) is a transcription factor that regulates genes involved in fatty acid metabolism. Here, we determined that the Adam10 promoter harbors PPAR response elements; that knockdown of PPAR alpha, but not PPAR beta or PPAR gamma, decreases the expression of Adam10; and that lentiviral overexpression of PPAR alpha restored ADAM10 expression in Ppara(-/-) neurons. Gemfibrozil, an agonist of PPAR alpha, induced the recruitment of PPAR alpha:retinoid x receptor alpha, but not PPAR gamma coactivator 1 alpha (PGC1 alpha), to the Adam10 promoter in wild-type mouse hippocampal neurons and shifted APP processing toward the alpha-secretase, as determined by augmented soluble APP alpha and decreased A beta production. Accordingly, Ppara(-/-) mice displayed elevated SDS-stable, endogenous A beta and A beta(1-42) relative to wild-type littermates, whereas 5XFAD mice null for PPAR alpha (5X/alpha(-/-)) exhibited greater cerebral A beta load relative to 5XFAD littermates. These results identify PPAR alpha as an important factor regulating neuronal ADAM10 expression and, thus, alpha-secretase proteolysis of APP.
C1 [Corbett, Grant T.] Rush Univ, Med Ctr, Dept Neurol Sci, Grad Program Neurosci, Chicago, IL 60612 USA.
[Corbett, Grant T.; Pahan, Kalipada] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA.
[Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Pahan, Kalipada] Jesse Brown Vet Affairs Med Ctr, Div Res & Dev, Chicago, IL 60612 USA.
RP Pahan, K (reprint author), Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA.
EM Kalipada_Pahan@rush.edu
OI Corbett, Grant/0000-0003-3606-9686
FU National Institutes on Aging Predoctoral training Grant [5T32 AG000269];
National Institutes of Health [AT6681, NS083054]; Veteran Affairs
[I01BX003033-01]
FX We thank Dustin Wakeman and Benjamin Hiller for their assistance with
histological preparation. A portion of this work was completed while
G.T.C. was supported by a National Institutes on Aging Predoctoral
training Grant (5T32 AG000269). This work was supported by grants from
National Institutes of Health (AT6681 and NS083054) and a merit award
from Veteran Affairs (I01BX003033-01).
NR 30
TC 8
Z9 8
U1 2
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 JUL 7
PY 2015
VL 112
IS 27
BP 8445
EP 8450
DI 10.1073/pnas.1504890112
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CM2QU
UT WOS:000357527600079
PM 26080426
ER
PT J
AU Bonaventura, J
Navarro, G
Casado-Anguera, V
Azdad, K
Rea, W
Moreno, E
Brugarolas, M
Mallol, J
Canela, EI
Lluis, C
Cortees, A
Volkow, ND
Schiffmann, SN
Ferre, S
Casado, V
AF Bonaventura, Jordi
Navarro, Gemma
Casado-Anguera, Veronica
Azdad, Karima
Rea, William
Moreno, Estefania
Brugarolas, Marc
Mallol, Josefa
Canela, Enric I.
Lluis, Carme
Cortes, Antoni
Volkow, Nora D.
Schiffmann, Serge N.
Ferre, Sergi
Casado, Vicent
TI Allosteric interactions between agonists and antagonists within the
adenosine A(2A) receptor-dopamine D-2 receptor heterotetramer
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE adenosine A(2A) receptor; dopamine D-2 receptor; caffeine; GPCR
heteromers
ID HETEROMERS; CAFFEINE; DETERMINANTS; COMPLEXES; AFFINITY
AB Adenosine A(2A) receptor (A(2A)R)-dopamine D-2 receptor (D2R) heteromers are key modulators of striatal neuronal function. It has been suggested that the psychostimulant effects of caffeine depend on its ability to block an allosteric modulation within the A(2A)R-D2R heteromer, by which adenosine decreases the affinity and intrinsic efficacy of dopamine at the D2R. We describe novel unsuspected allosteric mechanisms within the heteromer by which not only A(2A)R agonists, but also A(2A)R antagonists, decrease the affinity and intrinsic efficacy of D2R agonists and the affinity of D2R antagonists. Strikingly, these allosteric modulations disappear on agonist and antagonist coadministration. This can be explained by a model that considers A(2A)R-D2R heteromers as heterotetramers, constituted by A(2A)R and D2R homodimers, as demonstrated by experiments with bioluminescence resonance energy transfer and bimolecular fluorescence and bioluminescence complementation. As predicted by the model, high concentrations of A(2A)R antagonists behaved as A(2A)R agonists and decreased D2R function in the brain.
C1 [Bonaventura, Jordi; Navarro, Gemma; Casado-Anguera, Veronica; Moreno, Estefania; Brugarolas, Marc; Mallol, Josefa; Canela, Enric I.; Lluis, Carme; Cortes, Antoni; Casado, Vicent] Univ Barcelona, Fac Biol, Dept Biochem & Mol Biol, E-08028 Barcelona, Spain.
[Bonaventura, Jordi; Navarro, Gemma; Casado-Anguera, Veronica; Moreno, Estefania; Brugarolas, Marc; Mallol, Josefa; Canela, Enric I.; Lluis, Carme; Cortes, Antoni; Casado, Vicent] Univ Barcelona, Ctr Invest Biomed Red Enfermedades Neurodegenerat, E-08028 Barcelona, Spain.
[Bonaventura, Jordi; Navarro, Gemma; Casado-Anguera, Veronica; Moreno, Estefania; Brugarolas, Marc; Mallol, Josefa; Canela, Enric I.; Lluis, Carme; Cortes, Antoni; Casado, Vicent] Univ Barcelona, Inst Biomed, E-08028 Barcelona, Spain.
[Bonaventura, Jordi; Rea, William; Ferre, Sergi] NIDA, Integrat Neurobiol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Azdad, Karima; Schiffmann, Serge N.] Univ Libre Bruxelles, Inst Neurosci, Neurophysiol Lab, B-1070 Brussels, Belgium.
[Volkow, Nora D.] NIAAA, NIH, Bethesda, MD 20892 USA.
RP Ferre, S (reprint author), NIDA, Integrat Neurobiol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
EM sferre@intra.nida.nih.gov; vcasado@ub.edu
RI Casado, Vicent/K-1660-2014; Ferre, Sergi/K-6115-2014; Canela, Enric
I./M-8726-2013;
OI Ferre, Sergi/0000-0002-1747-1779; Canela, Enric I./0000-0003-4992-7440;
Bonaventura, Jordi/0000-0002-4745-0151
FU Government of Catalonia [2009-SGR-12]; Centro de Investigacion Biomedica
en Red sobre Enfermedades Neurodegenerativas [CB06/05/0064]; Spanish
Ministerio de Ciencia y Teconolgia [SAF 2011-23813]; National Institute
on Drug Abuse
FX We acknowledge the technical assistance of Jasmina Jimenez and Edgar
Angelats, and thank Dr. Javier Meana and Dr. Joan Salles (University of
the Basque Country) for providing the human samples. This study was
supported by the National Institute on Drug Abuse and grants from the
Government of Catalonia (2009-SGR-12), Centro de Investigacion Biomedica
en Red sobre Enfermedades Neurodegenerativas (CB06/05/0064), and the
Spanish Ministerio de Ciencia y Teconolgia (SAF 2011-23813).
NR 29
TC 18
Z9 18
U1 4
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 JUL 7
PY 2015
VL 112
IS 27
BP E3609
EP E3618
DI 10.1073/pnas.1507704112
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CM2QU
UT WOS:000357527600021
PM 26100888
ER
PT J
AU Rojas, M
Vasconcelos, G
Dever, TE
AF Rojas, Margarito
Vasconcelos, Gabriel
Dever, Thomas E.
TI An eIF2 alpha-binding motif in protein phosphatase 1 subunit GADD34 and
its viral orthologs is required to promote dephosphorylation of eIF2
alpha
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE DP71L; CReP; canarypox; PP1; PKR
ID INDUCED GENE-EXPRESSION; TRANSFER-RNA BINDING; INITIATION-FACTOR 2;
TRANSLATION INITIATION; ALPHA-SUBUNIT; SACCHAROMYCES-CEREVISIAE;
REGULATORY SUBUNITS; CATALYTIC SUBUNIT; CRYSTAL-STRUCTURE; STRUCTURAL
BASIS
AB Transient protein synthesis inhibition, mediated by phosphorylation of the a subunit of eukaryotic translation initiation factor 2 (eIF2 alpha), is an important protective mechanism cells use during stress conditions. Following relief of the stress, the growth arrest and DNA damage-inducible protein GADD34 associates with the broadly acting serine/threonine protein phosphatase 1 (PP1) to dephosphorylate eIF2 alpha. Whereas the PP1-binding motif on GADD34 has been defined, it remains to be determined how GADD34 directs PP1 to specifically dephosphorylate eIF2 alpha. In this report, we map a novel eIF2 alpha-binding motif to the C terminus of GADD34 in a region distinct from where PP1 binds to GADD34. This motif is characterized by the consensus sequence Rx[Gnl]x(1-2)Wxxx[Arlv]x [Dn][Rg]xRFxx[Rlvk][Ivc], where capital letters are preferred and x is any residue. Point mutations altering the eIF2 alpha-binding motif impair the ability of GADD34 to interact with eIF2 alpha, promote eIF2 alpha dephosphorylation, and suppress PKR toxicity in yeast. Interestingly, this eIF2 alpha-docking motif is conserved among viral orthologs of GADD34, and is necessary for the proteins produced by African swine fever virus, Canarypox virus, and Herpes simplex virus to promote eIF2 alpha dephosphorylation. Taken together, these data indicate that GADD34 and its viral orthologs direct specific dephosphorylation of eIF2 alpha by interacting with both PP1 and eIF2 alpha through independent binding motifs.
C1 [Rojas, Margarito; Vasconcelos, Gabriel; 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, Eunice
Kennedy Shriver National Institute of Child Health and Human Development
FX We thank Anne-Claude Gingras and Shirish Shenolikar for providing
reagents, Chune Cao for technical support, and Alan Hinnebusch and
members of the T.E.D. and Hinnebusch laboratories for helpful
discussions. This work was supported, in part, by the Intramural
Research Program of the National Institutes of Health, Eunice Kennedy
Shriver National Institute of Child Health and Human Development (to
T.E.D.).
NR 50
TC 3
Z9 3
U1 1
U2 12
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 7
PY 2015
VL 112
IS 27
BP E3466
EP E3475
DI 10.1073/pnas.1501557112
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CM2QU
UT WOS:000357527600006
PM 26100893
ER
PT J
AU Bellay, T
Klaus, A
Seshadri, S
Plenz, D
AF Bellay, Timothy
Klaus, Andreas
Seshadri, Saurav
Plenz, Dietmar
TI Irregular spiking of pyramidal neurons organizes as scale-invariant
neuronal avalanches in the awake state
SO ELIFE
LA English
DT Article
ID RANGE TEMPORAL CORRELATIONS; BALANCED CORTICAL NETWORKS; IN-VIVO
ELECTROPORATION; BARREL CORTEX; NEURAL-NETWORKS; ACTIVITY PATTERNS; CELL
ASSEMBLIES; DYNAMIC-RANGE; BEHAVING MICE; HUMAN BRAIN
AB Spontaneous fluctuations in neuronal activity emerge at many spatial and temporal scales in cortex. Population measures found these fluctuations to organize as scale-invariant neuronal avalanches, suggesting cortical dynamics to be critical. Macroscopic dynamics, though, depend on physiological states and are ambiguous as to their cellular composition, spatiotemporal origin, and contributions from synaptic input or action potential (AP) output. Here, we study spontaneous firing in pyramidal neurons (PNs) from rat superficial cortical layers in vivo and in vitro using 2-photon imaging. As the animal transitions from the anesthetized to awake state, spontaneous single neuron firing increases in irregularity and assembles into scale-invariant avalanches at the group level. In vitro spike avalanches emerged naturally yet required balanced excitation and inhibition. This demonstrates that neuronal avalanches are linked to the global physiological state of wakefulness and that cortical resting activity organizes as avalanches from firing of local PN groups to global population activity.
C1 [Bellay, Timothy; Klaus, Andreas; Seshadri, Saurav; Plenz, Dietmar] NIH, Sect Crit Brain Dynam, Bethesda, MD 20892 USA.
RP Plenz, D (reprint author), NIH, Sect Crit Brain Dynam, Bldg 10, Bethesda, MD 20892 USA.
EM plenzd@mail.nih.gov
OI Klaus, Andreas/0000-0002-4133-351X
FU National Institute of Mental Health (NIMH) Division of Intramural
Research
FX National Institute of Mental Health (NIMH) Division of Intramural
Research Timothy Bellay, Andreas Klaus, Saurav Seshadri, Dietmar Plenz
NR 122
TC 9
Z9 9
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 JUL 7
PY 2015
VL 4
AR e07224
DI 10.7554/eLife.07224
PG 25
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA CM3NP
UT WOS:000357589400001
PM 26151674
ER
PT J
AU Kuehn, BM
Varmus, H
AF Kuehn, Bridget M.
Varmus, Harold
TI Varmus Returns to His Roots in Cancer Genetics
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT News Item
C1 [Varmus, Harold] NIH, Bethesda, MD USA.
[Varmus, Harold] Mem Sloan Kettering Canc Ctr, New York, NY USA.
[Varmus, Harold] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUL 7
PY 2015
VL 314
IS 1
BP 13
EP 14
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA CM1QR
UT WOS:000357455900002
ER
PT J
AU Bayefsky, MJ
Saylor, KW
Berkman, BE
AF Bayefsky, Michelle J.
Saylor, Katherine W.
Berkman, Benjamin E.
TI Parental Consent for the Use of Residual Newborn Screening Bloodspots
Respecting Individual Liberty vs Ensuring Public Health
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
C1 [Bayefsky, Michelle J.; Berkman, Benjamin E.] NIH, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA.
[Saylor, Katherine W.] NHGRI, Div Policy Commun & Educ, NIH, Bethesda, MD 20892 USA.
[Berkman, Benjamin E.] NHGRI, Bioeth Core, NIH, Bethesda, MD 20892 USA.
RP Berkman, BE (reprint author), NIH, Ctr Clin, Dept Bioeth, 10 Ctr Dr,Bldg 10,Room 1C118, Bethesda, MD 20892 USA.
EM berkmanbe@mail.nih.gov
FU Intramural NIH HHS
NR 4
TC 4
Z9 4
U1 1
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUL 7
PY 2015
VL 314
IS 1
BP 21
EP 22
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA CM1QR
UT WOS:000357455900007
PM 26053685
ER
PT J
AU Drover, DR
Hammer, GB
Barrett, JS
Cohane, CA
Reece, T
Zajicek, A
Schulman, SR
AF Drover, David R.
Hammer, Gregory B.
Barrett, Jeffrey S.
Cohane, Carol A.
Reece, Tammy
Zajicek, Anne
Schulman, Scott R.
TI Evaluation of sodium nitroprusside for controlled hypotension in
children during surgery
SO FRONTIERS IN PHARMACOLOGY
LA English
DT Article
DE nitroprusside; pediatric; BPCA; cyanide toxicity; controlled hypotension
ID SPINAL SURGERY; METABOLISM; CYANIDE; AGENT; NITROGLYCERIN; THIOSULFATE;
ADOLESCENTS; NICARDIPINE; INFUSION
AB Purpose: (1) To define the onset and offset of the blood-pressure-lowering effects of sodium nitroprusside (SNP) for use in developing instructions for dose titration in children undergoing a surgical or medical procedure, and (2) to assess the safety of SNP administration in pediatric patients requiring controlled reduction of blood pressure.
Methods: We conducted a randomized, double-blind, parallel-group, dose-ranging, effect-controlled, multicenter study of intravenous (IV) infusions of SNP in pediatric patients < 17 years, who required controlled hypotension for at least 2 h while undergoing a surgical or medical procedure. A blinded SNP dose of 0.3, 1, 2, or 3 mu g/kg/min was infused for 30 min, followed by open-label administration for at least 90 min. Both infusions were titrated to effect.
Results: The final intent-to-treat group comprised 203 patients. Significant reductions in mean arterial pressure (MAP) from baseline were observed for all four doses at 20 and 25 min after the start of infusion (p <= 0.009 and p <= 0.010 for each time, respectively). Overall, 98.5% of the patients achieved the target MAP; 72.9% first achieved the target MAP during the blinded infusion. The mean infusion rate at target MAP was 1.07 mu g/kg/min.
Conclusion: We determined that 0.3 mu g/kg/m is a reasonable starting dose for SNP in pediatric patients requiring controlled hypotension. The infusion rate can then be increased to achieve the desired reduction in blood pressure. On the basis of our results, we found an average infusion rate of 1 mu g/kg/min might be appropriate. Of note, no cyanide toxicity was reported, and no measureable cyanide levels were detected in any blood samples obtained during the study.
C1 [Drover, David R.; Hammer, Gregory B.; Cohane, Carol A.] Stanford Univ, Dept Anesthesia Perioperat & Pain Med, Sch Med, Stanford, CA 94305 USA.
[Barrett, Jeffrey S.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Clin Pharmacol & Therapeut Div, Philadelphia, PA 19104 USA.
[Barrett, Jeffrey S.] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA.
[Reece, Tammy] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA.
[Zajicek, Anne] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Schulman, Scott R.] Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA.
RP Drover, DR (reprint author), SUMC, Dept Anesthesia, 300 Pasteur Dr, Stanford, CA 94305 USA.
EM ddrover@stanford.edu
FU NICHD, Rockville, Maryland [NO1-HD-4-3385]
FX NO1-HD-4-3385 (NICHD, Rockville, Maryland).
NR 24
TC 1
Z9 1
U1 0
U2 2
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1663-9812
J9 FRONT PHARMACOL
JI Front. Pharmacol.
PD JUL 6
PY 2015
VL 6
AR 136
DI 10.3389/fphar.2015.00136
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CW9NK
UT WOS:000365325300001
PM 26217225
ER
PT J
AU Beaulieu, LM
Clancy, L
Tanriverdi, K
Benjamin, EJ
Kramer, CD
Weinberg, EO
He, XB
Mekasha, S
Mick, E
Ingalls, RR
Genco, CA
Freedman, JE
AF Beaulieu, Lea M.
Clancy, Lauren
Tanriverdi, Kahraman
Benjamin, Emelia J.
Kramer, Carolyn D.
Weinberg, Ellen O.
He, Xianbao
Mekasha, Samrawit
Mick, Eric
Ingalls, Robin R.
Genco, Caroline A.
Freedman, Jane E.
TI Specific Inflammatory Stimuli Lead to Distinct Platelet Responses in
Mice and Humans
SO PLOS ONE
LA English
DT Article
ID POLYMERASE-CHAIN-REACTION; SET ENRICHMENT ANALYSIS;
CORONARY-HEART-DISEASE; E-DEFICIENT MICE; APOLIPOPROTEIN-E;
PORPHYROMONAS-GINGIVALIS; CHLAMYDIA-PNEUMONIAE;
CHLAMYDOPHILA-PNEUMONIAE; ATHEROSCLEROTIC LESIONS;
CARDIOVASCULAR-DISEASE
AB Introduction
Diverse and multi-factorial processes contribute to the progression of cardiovascular disease. These processes affect cells involved in the development of this disease in varying ways, ultimately leading to atherothrombosis. The goal of our study was to compare the differential effects of specific stimuli - two bacterial infections and a Western diet - on platelet responses in ApoE(-/-) mice, specifically examining inflammatory function and gene expression. Results from murine studies were verified using platelets from participants of the Framingham Heart Study (FHS; n = 1819 participants).
Methods
Blood and spleen samples were collected at weeks 1 and 9 from ApoE(-/-) mice infected with Porphyromonas gingivalis or Chlamydia pneumoniae and from mice fed a Western diet for 9 weeks. Transcripts based on data from a Western diet in ApoE(-/-) mice were measured in platelet samples from FHS using high throughput qRT-PCR.
Results
At week 1, both bacterial infections increased circulating platelet-neutrophil aggregates. At week 9, these cells individually localized to the spleen, while Western diet resulted in increased platelet-neutrophil aggregates in the spleen only. Microarray analysis of platelet RNA from infected or Western diet-fed mice at week 1 and 9 showed differential profiles. Genes, such as Serpina1a, Ttr, Fgg, Rpl21, and Alb, were uniquely affected by infection and diet. Results were reinforced in platelets obtained from participants of the FHS.
Conclusion
Using both human studies and animal models, results demonstrate that variable sources of inflammatory stimuli have the ability to influence the platelet phenotype in distinct ways, indicative of the diverse function of platelets in thrombosis, hemostasis, and immunity.
C1 [Beaulieu, Lea M.; Clancy, Lauren; Tanriverdi, Kahraman; Freedman, Jane E.] Univ Massachusetts, Sch Med, Dept Med, Div Cardiovasc Med, Worcester, MA 01655 USA.
[Benjamin, Emelia J.] NHLBI, Framingham, MA USA.
[Benjamin, Emelia J.] Boston Univ, Framingham Heart Inst, Framingham, MA USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Cardiol & Prevent Med Sect, Boston, MA 02118 USA.
[Kramer, Carolyn D.; Weinberg, Ellen O.; Ingalls, Robin R.; Genco, Caroline A.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[He, Xianbao; Genco, Caroline A.] Boston Univ, Sch Med, Dept Med, Infect Dis Sect, Boston, MA 02118 USA.
[Mekasha, Samrawit; Ingalls, Robin R.] Boston Med Ctr, Boston, MA USA.
[Mick, Eric] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA.
[Genco, Caroline A.] Boston Univ, Sch Med, Dept Microbiol, Boston, MA 02118 USA.
RP Beaulieu, LM (reprint author), Univ Massachusetts, Sch Med, Dept Med, Div Cardiovasc Med, Worcester, MA 01655 USA.
EM lea.beaulieu@umassmed.edu
OI Benjamin, Emelia/0000-0003-4076-2336
FU National Institutes of Health [N01-HC 25195, RFA-HL-12-008,
RFA-RM-12-013, P-01-HL085381, P01 AI078894, 1RO1 HL64753, R01 HL076784,
1 R01 AG028321]
FX The work presented was supported by N01-HC 25195, RFA-HL-12-008 (JEF,
EM), RFA-RM-12-013 (JEF), P-01-HL085381 (JEF), P01 AI078894 (LMB, CDK,
EOW, XH, SM, RI, CAG, and JEF), 1RO1 HL64753, R01 HL076784, and 1 R01
AG028321 (EJB), from the National Institutes of Health (www.nih.gov).
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 50
TC 1
Z9 1
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 JUL 6
PY 2015
VL 10
IS 7
AR e0131688
DI 10.1371/journal.pone.0131688
PG 22
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN1DQ
UT WOS:000358157600129
PM 26148065
ER
PT J
AU Crossey, E
Frietze, K
Narum, DL
Peabody, DS
Chackerian, B
AF Crossey, Erin
Frietze, Kathryn
Narum, David L.
Peabody, David S.
Chackerian, Bryce
TI Identification of an Immunogenic Mimic of a Conserved Epitope on the
Plasmodium falciparum Blood Stage Antigen AMA1 Using Virus-Like Particle
(VLP) Peptide Display
SO PLOS ONE
LA English
DT Article
ID APICAL MEMBRANE ANTIGEN-1; INHIBITORY MONOCLONAL-ANTIBODY; MALARIA
VACCINE; ERYTHROCYTE INVASION; DIVERSE PEPTIDES; FULL-LENGTH; PROTEIN;
AFFINITY; LOCALIZATION; EXPRESSION
AB We have developed a peptide display platform based on VLPs of the RNA bacteriophage MS2 that combines the high immunogenicity of VLP display with affinity selection capabilities. Random peptides can be displayed on the VLP surface by genetically inserting sequences into a surface-exposed loop of the viral coat protein. VLP-displayed peptides can then be isolated by selection using antibodies, and the VLP selectants can then be used directly as immunogens. Here, we investigated the ability of this platform to identify mimotopes of a highly conserved conformational epitope present on the Plasmodium falciparum blood-stage protein AMA1. Using 4G2, a monoclonal antibody that binds to this epitope and is a potent inhibitor of erythrocyte invasion, we screened three different VLP-peptide libraries and identified specific VLPs that bound strongly to the selecting mAb. We then tested the ability of a handful of selected VLPs to elicit anti-AMA1 antibody responses in mice. Most of the selected VLPs failed to reliably elicit AMA1 specific antibodies. However, one VLP consistently induced antibodies that cross-reacted with AMA1. Surprisingly, this VLP bound to 4G2 more weakly than the other selectants we identified. Taken together, these data demonstrate that VLP-peptide display can identify immunogenic mimics of a complex conformational epitope and illustrate the promise and challenges of this approach.
C1 [Crossey, Erin; Frietze, Kathryn; Peabody, David S.; Chackerian, Bryce] Univ New Mexico, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA.
[Narum, David L.] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD 20852 USA.
RP Chackerian, B (reprint author), Univ New Mexico, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA.
EM bchackerian@salud.unm.edu
FU NIH [R01 AI083305]; NIAID, NIH; University of New Mexico Biology of
Infectious Diseases and Inflammation Training Grant [T31-AI007538]
FX This research was supported by NIH grant R01 AI083305 (to BC) and by the
Intramural Research Program of NIAID, NIH. EC was supported by the
University of New Mexico Biology of Infectious Diseases and Inflammation
Training Grant (T31-AI007538). The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 38
TC 4
Z9 4
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 JUL 6
PY 2015
VL 10
IS 7
AR e0132560
DI 10.1371/journal.pone.0132560
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN1DQ
UT WOS:000358157600300
PM 26147502
ER
PT J
AU Mucker, EM
Chapman, J
Huzella, LM
Huggins, JW
Shamblin, J
Robinson, CG
Hensley, LE
AF Mucker, Eric M.
Chapman, Jennifer
Huzella, Louis M.
Huggins, John W.
Shamblin, Joshua
Robinson, Camenzind G.
Hensley, Lisa E.
TI Susceptibility of Marmosets (Callithrix jacchus) to Monkeypox Virus: A
Low Dose Prospective Model for Monkeypox and Smallpox Disease
SO PLOS ONE
LA English
DT Article
ID NONHUMAN PRIMATE MODEL; VACCINIA VIRUS; POXVIRUS INFECTION; IN-VITRO;
PROTECTION; COMPLEMENT; PATHOLOGY; VARIOLA; ST-246; VACCINATION
AB Although current nonhuman primate models of monkeypox and smallpox diseases provide some insight into disease pathogenesis, they require a high titer inoculum, use an unnatural route of infection, and/or do not accurately represent the entire disease course. This is a concern when developing smallpox and/or monkeypox countermeasures or trying to understand host pathogen relationships. In our studies, we altered half of the test system by using a New World nonhuman primate host, the common marmoset. Based on dose finding studies, we found that marmosets are susceptible to monkeypox virus infection, produce a high viremia, and have pathological features consistent with smallpox and monkeypox in humans. The low dose (48 plaque forming units) required to elicit a uniformly lethal disease and the extended incubation (preclinical signs) are unique features among nonhuman primate models utilizing monkeypox virus. The uniform lethality, hemorrhagic rash, high viremia, decrease in platelets, pathology, and abbreviated acute phase are reflective of early-type hemorrhagic smallpox.
C1 [Mucker, Eric M.; Huggins, John W.; Shamblin, Joshua] US Army Med Res Inst Infect Dis, Div Virol, Ft Detrick, MD 21701 USA.
[Chapman, Jennifer] Joint Pathol Ctr, Silver Spring, MD USA.
[Huzella, Louis M.; Hensley, Lisa E.] NIAID, Integrated Res Facil, Ft Detrick, MD USA.
[Robinson, Camenzind G.] US Army Med Res Inst Infect Dis, Div Pathol, Ft Detrick, MD USA.
[Mucker, Eric M.] Tulane Univ, Sch Med, New Orleans, LA 70112 USA.
RP Mucker, EM (reprint author), US Army Med Res Inst Infect Dis, Div Virol, Ft Detrick, MD 21701 USA.
EM eric.m.mucker.ctr@mail.mil
FU United States Army Medical Research Institute of Infectious Diseases
FX This work was internally funded by the United States Army Medical
Research Institute of Infectious Diseases. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 46
TC 1
Z9 1
U1 0
U2 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 JUL 6
PY 2015
VL 10
IS 7
AR e0131742
DI 10.1371/journal.pone.0131742
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN1DQ
UT WOS:000358157600139
PM 26147658
ER
PT J
AU Sharma, V
Jordan, JJ
Ciribilli, Y
Resnick, MA
Bisio, A
Inga, A
AF Sharma, Vasundhara
Jordan, Jennifer J.
Ciribilli, Yari
Resnick, Michael A.
Bisio, Alessandra
Inga, Alberto
TI Quantitative Analysis of NF-kappa B Transactivation Specificity Using a
Yeast-Based Functional Assay
SO PLOS ONE
LA English
DT Article
ID TRANSCRIPTION FACTORS; DNA-BINDING; SACCHAROMYCES-CEREVISIAE; RESPONSE
ELEMENTS; IN-VIVO; P53; COMPLEX; PROTEINS; PARTHENOLIDE; SEQUENCES
AB The NF-kappa B transcription factor family plays a central role in innate immunity and inflammation processes and is frequently dysregulated in cancer. We developed an NF-kappa B functional assay in yeast to investigate the following issues: transactivation specificity of NF-kappa B proteins acting as homodimers or heterodimers; correlation between transactivation capacity and in vitro DNA binding measurements; impact of co-expressed interacting proteins or of small molecule inhibitors on NF-kappa B-dependent transactivation. Full-length p65 and p50 cDNAs were cloned into centromeric expression vectors under inducible GAL1 promoter in order to vary their expression levels. Since p50 lacks a transactivation domain (TAD), a chimeric construct containing the TAD derived from p65 was also generated (p50TAD) to address its binding and transactivation potential. The p50TAD and p65 had distinct transactivation specificities towards seventeen different kappa B response elements (kappa B-REs) where single nucleotide changes could greatly impact transactivation. For four kappa B-REs, results in yeast were predictive of transactivation potential measured in the human MCF7 cell lines treated with the NF-kappa B activator TNF alpha. Transactivation results in yeast correlated only partially with in vitro measured DNA binding affinities, suggesting that features other than strength of interaction with naked DNA affect transactivation, although factors such as chromatin context are kept constant in our isogenic yeast assay. The small molecules BAY11-7082 and ethyl-pyruvate as well as expressed IkB alpha protein acted as NF-kappa B inhibitors in yeast, more strongly towards p65. Thus, the yeast-based system can recapitulate NF-kappa B features found in human cells, thereby providing opportunities to address various NF-kappa B functions, interactions and chemical modulators.
C1 [Sharma, Vasundhara; Jordan, Jennifer J.; Ciribilli, Yari; Bisio, Alessandra; Inga, Alberto] Univ Trento, Lab Transcript Networks, Ctr Integrat Biol CIBIO, Trento, Italy.
[Resnick, Michael A.] Natl Inst Environm Hlth Sci, Chromosome Stabil Grp, Res Triangle Pk, NC USA.
RP Bisio, A (reprint author), Univ Trento, Lab Transcript Networks, Ctr Integrat Biol CIBIO, Trento, Italy.
EM bisio@science.unitn.it; inga@science.unitn.it
OI sharma, vineet/0000-0002-2958-6215
FU intramural project "ADARE" (NIH) [RFA RM 06 004]; Italian Association
for Cancer Research, AIRC [IG 12869]
FX This work was funded by intramural project "ADARE" to MAR and Jonathan
Freedman (NIH, RFA RM 06 004) and partially supported by the Italian
Association for Cancer Research, AIRC (IG 12869 to AI). The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 57
TC 1
Z9 1
U1 1
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 JUL 6
PY 2015
VL 10
IS 7
AR e0130170
DI 10.1371/journal.pone.0130170
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN1DQ
UT WOS:000358157600031
PM 26147604
ER
PT J
AU Solje, E
Aaltokallio, H
Koivumaa-Honkanen, H
Suhonen, NM
Moilanen, V
Kiviharju, A
Traynor, B
Tienari, PJ
Hartikainen, P
Remes, AM
AF Solje, Eino
Aaltokallio, Heidi
Koivumaa-Honkanen, Heli
Suhonen, Noora M.
Moilanen, Virpi
Kiviharju, Anna
Traynor, Bryan
Tienari, Pentti J.
Hartikainen, Paivi
Remes, Anne M.
TI The Phenotype of the C9ORF72 Expansion Carriers According to Revised
Criteria for bvFTD
SO PLOS ONE
LA English
DT Article
ID HEXANUCLEOTIDE REPEAT EXPANSION; FRONTOTEMPORAL DEMENTIA;
DIAGNOSTIC-CRITERIA; BEHAVIORAL VARIANT; ALS; SENSITIVITY; MUTATIONS;
FEATURES; FTD
AB Background
The C9ORF72 expansion is one of the most common genetic etiologies observed with behavioural variant frontotemporal dementia (bvFTD). Revised diagnostic criteria for bvFTD (FTDC) were recently introduced but only a few studies have evaluated the accuracy of these criteria.
Objective
The objective of the study was to evaluate the applicability of the FTDC criteria and assess the psychiatric history of these patients.
Methods
The study examined 36 patients carrying the C9ORF72 expansion and suffering from bvFTD (N = 32) or from bvFTD with motor neuron disease (bvFTD-MND, N = 4). Neuropsychological, neuropsychiatric, structural brain imaging and PET/SPECT data were evaluated.
Results
We found 0.75 sensitivity (SD 0.44, 95% CI 0.57-0.87) for possible bvFTD and 0.64 (SD 0.44, 95% CI 0.57-0.87) for probable bvFTD. The sensitivity was even higher in bvFTD patients without MND, i.e., 0.81 for possible bvFTD and 0.69 for probable bvFTD. PET/SPECT was normal in 17.6% of scanned patients with bvFTD. A history of psychiatric symptoms (psychotic and/or mood symptoms) was detected in 61% of cases.
Conclusions
The FTDC possible and probable bvFTD criteria seem to identify the majority of the C9ORF72 expansion carriers with bvFTD, even though they exhibit only a limited number of behavioral criteria but a significant amount of psychiatric symptoms. The presence of a normal PET/SPECT does not exclude the possibility the C9ORF72 associated bvFTD.
C1 [Solje, Eino; Aaltokallio, Heidi; Remes, Anne M.] Univ Eastern Finland, Inst Clin Med Neurol, Kuopio, Finland.
[Koivumaa-Honkanen, Heli] Univ Eastern Finland, Inst Clin Med Psychiat, Kuopio, Finland.
[Koivumaa-Honkanen, Heli] Kuopio Univ Hosp, Dept Psychiat, SF-70210 Kuopio, Finland.
[Koivumaa-Honkanen, Heli] South Savonia Hosp Dist, Dept Psychiat, Mikkeli, Finland.
[Koivumaa-Honkanen, Heli] North Karelia Cent Hosp, Dept Psychiat, Joensuu, Finland.
[Koivumaa-Honkanen, Heli] SOSTERI, Dept Psychiat, Savonlinna, Finland.
[Koivumaa-Honkanen, Heli] SOTE, Dept Psychiat, Iisalmi, Finland.
[Koivumaa-Honkanen, Heli] Lapland Hosp Dist, Dept Psychiat, Rovaniemi, Finland.
[Suhonen, Noora M.; Moilanen, Virpi] Oulu Univ Hosp, Dept Neurol, Oulu, Finland.
[Kiviharju, Anna; Tienari, Pentti J.] Univ Helsinki, Dept Neurol, Cent Hosp, Mol Neurol,Res Programs Unit, Helsinki, Finland.
[Traynor, Bryan] NIA, Neuromuscular Dis Res Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Traynor, Bryan] Johns Hopkins Univ, Brain Sci Inst, Baltimore, MD USA.
[Hartikainen, Paivi; Remes, Anne M.] Kuopio Univ Hosp, Dept Neurol, SF-70210 Kuopio, Finland.
RP Remes, AM (reprint author), Univ Eastern Finland, Inst Clin Med Neurol, Kuopio, Finland.
EM anne.remes@uef.fi
FU Kuopio University Hospital; Helsinki University Central Hospital;
Finnish Academy; Sigrid Juselius Foundation; Finnish Medical Foundation;
Finnish Alzheimer's Research Foundation; Intramural Research Programs of
the NIH and National Institute on Aging [Z01-AG000949-02]; ALS
Association, AriSLA, Packard Center for ALS research, FIGC, Microsoft
Research; Myasthenia Gravis Foundation
FX This work was supported by grants from the Kuopio University Hospital,
Helsinki University Central Hospital, the Finnish Academy, the Sigrid
Juselius Foundation, the Finnish Medical Foundation, the Finnish
Alzheimer's Research Foundation, the Intramural Research Programs of the
NIH and National Institute on Aging (Z01-AG000949-02), the ALS
Association, AriSLA, Packard Center for ALS research, FIGC, Microsoft
Research and the Myasthenia Gravis Foundation. The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 18
TC 2
Z9 2
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 6
PY 2015
VL 10
IS 7
AR e0131817
DI 10.1371/journal.pone.0131817
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN1DQ
UT WOS:000358157600149
PM 26146826
ER
PT J
AU ZeRuth, GT
Williams, JG
Cole, YC
Jetten, AM
AF ZeRuth, Gary T.
Williams, Jason G.
Cole, Yasemin C.
Jetten, Anton M.
TI HECT E3 Ubiquitin Ligase Itch Functions as a Novel Negative Regulator of
Gli-Similar 3 (Glis3) Transcriptional Activity
SO PLOS ONE
LA English
DT Article
ID NEONATAL DIABETES-MELLITUS; PROLINE-RICH LIGANDS; BETA-CELL FUNCTION;
ZINC-FINGER; WW-DOMAINS; CONGENITAL HYPOTHYROIDISM; KIDNEY-DISEASE; 26S
PROTEASOME; NEDD4 FAMILY; PROTEIN
AB The transcription factor Gli-similar 3 (Glis3) plays a critical role in the generation of pancreatic B cells and the regulation insulin gene transcription and has been implicated in the development of several pathologies, including type 1 and 2 diabetes and polycystic kidney disease. However, little is known about the proteins and posttranslational modifications that regulate or mediate Glis3 transcriptional activity. In this study, we identify by mass-spectrometry and yeast 2-hybrid analyses several proteins that interact with the N-terminal region of Glis3. These include the WW-domain-containing HECT E3 ubiquitin ligases, Itch, Smurf2, and Nedd4. The interaction between Glis3 and the HECT E3 ubiquitin ligases was verified by co-immunoprecipitation assays and mutation analysis. All three proteins interact through their WW-domains with a PPxY motif located in the Glis3 N-terminus. However, only Itch significantly contributed to Glis3 polyubiquitination and reduced Glis3 stability by enhancing its proteasomal degradation. Itch-mediated degradation of Glis3 required the PPxY motif-dependent interaction between Glis3 and the WW-domains of Itch as well as the presence of the Glis3 zinc finger domains. Transcription analyses demonstrated that Itch dramatically inhibited Glis3-mediated transactivation and endogenous Ins2 expression by increasing Glis3 protein turnover. Taken together, our study identifies Itch as a critical negative regulator of Glis3-mediated transcriptional activity. This regulation provides a novel mechanism to modulate Glis3-driven gene expression and suggests that it may play a role in a number of physiological processes controlled by Glis3, such as insulin transcription, as well as in Glis3-associated diseases.
C1 [ZeRuth, Gary T.; Cole, Yasemin C.; Jetten, Anton M.] NIEHS, Cell Biol Sect, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA.
[Williams, Jason G.] NIEHS, Mass Spectrometry Grp, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA.
RP Jetten, AM (reprint author), NIEHS, Cell Biol Sect, Div Intramural Res, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM jetten@niehs.nih.gov
OI Jetten, Anton/0000-0003-0954-4445
FU Intramural Research Program of the National Institute of Environmental
Health Sciences, the National Institutes of Health [Z01-ES-100485]
FX This research was supported by the Intramural Research Program of the
National Institute of Environmental Health Sciences, the National
Institutes of Health [Z01-ES-100485].
NR 65
TC 2
Z9 2
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 6
PY 2015
VL 10
IS 7
AR e0131303
DI 10.1371/journal.pone.0131303
PG 22
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN1DQ
UT WOS:000358157600087
PM 26147758
ER
PT J
AU Lim, JM
Lee, KS
Woo, HA
Kang, D
Rhee, SG
AF Lim, Jung Mi
Lee, Kyung S.
Woo, Hyun Ae
Kang, Dongmin
Rhee, Sue Goo
TI Control of the pericentrosomal H2O2 level by peroxiredoxin I is critical
for mitotic progression
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
ID CELL-CYCLE; MAMMALIAN PEROXIREDOXIN; REDOX MODULATION; NADPH OXIDASES;
MELANOMA-CELLS; GROWTH-FACTORS; PHOSPHATASE; MITOSIS; PHOSPHORYLATION;
EXIT
AB Proteins associated with the centrosome play key roles in mitotic progression in mammalian cells. The activity of Cdkl-opposing phosphatases at the centrosome must be inhibited during early mitosis to prevent premature dephosphorylation of Cdhl-an activator of the ubiquitin ligase anaphase-promoting complex/cyclosome and the consequent premature degradation of mitotic activators. In this paper, we show that reversible oxidative inactivation of centrosome-bound protein phosphatases such as Cdcl 4B by H2O2 is likely responsible for this inhibition. The intracellular concentration of H2O2 increases as the cell cycle progresses. Whereas the centrosome is shielded from H2O2 through its association with the H2O2-eliminating enzyme peroxiredoxin I (Prxl) during interphase, the centrosome-associated Prxl is selectively inactivated through phosphorylation by Cdkl during early mitosis, thereby exposing the centrosome to H2O2 and facilitating inactivation of centrosome-bound phosphatases. Dephosphorylation of Prxl by okadaic acid sensitive phosphatases during late mitosis again shields the centrosome from H2O2 and thereby allows the reactivation of Cdkl-opposing phosphatases at the organelle.
C1 [Lim, Jung Mi; Woo, Hyun Ae; Kang, Dongmin] Ewha Womans Univ, Div Life & Pharmaceut Sci, Seoul 120750, South Korea.
[Lee, Kyung S.] NCI, Lab Metab, Bethesda, MD 20892 USA.
[Rhee, Sue Goo] Yonsei Univ, Yonsei Biomed Res Inst, Seoul 120749, South Korea.
RP Kang, D (reprint author), Ewha Womans Univ, Div Life & Pharmaceut Sci, Seoul 120750, South Korea.
EM dkang@ewha.ac.kr; rheesg@yuhs.ac
FU Korean Science and Engineering Foundation (National Honor Scientist
program) [2006-05106]; National Research Foundation of Korea (Basic
Science Research program) [2011-0010514, 2012R1A1 A2002268]; Korean
Science and Engineering Foundation (BioRDprogram)
[M10642040001-07N4204-00110]
FX This study was supported by grants from the Korean Science and
Engineering Foundation (National Honor Scientist program grant
2006-05106 and BioR&Dprogram grant M10642040001-07N4204-00110 to S.G.
Rhee) and the National Research Foundation of Korea (Basic Science
Research program grants 2011-0010514 and 2012R1A1 A2002268 to D. Kong).
NR 51
TC 5
Z9 5
U1 0
U2 6
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA
SN 0021-9525
EI 1540-8140
J9 J CELL BIOL
JI J. Cell Biol.
PD JUL 6
PY 2015
VL 210
IS 1
BP 23
EP 33
DI 10.1083/jcb.201412068
PG 11
WC Cell Biology
SC Cell Biology
GA CM5XZ
UT WOS:000357763600006
PM 26150388
ER
PT J
AU Lerit, DA
Jordan, HA
Poulton, JS
Fagerstrom, CJ
Galletta, BJ
Peifer, M
Rusan, NM
AF Lerit, Dorothy A.
Jordan, Holly A.
Poulton, John S.
Fagerstrom, Carey J.
Galletta, Brian J.
Peifer, Mark
Rusan, Nasser M.
TI Interphase centrosome organization by the PLP-Cnn scaffold is required
for centrosome function
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
ID EARLY DROSOPHILA EMBRYOGENESIS; GAMMA-TUBULIN COMPLEXES; PERICENTRIOLAR
MATERIAL; MICROTUBULE ORGANIZATION; CENTRIOLAR PROTEIN; MITOTIC ENTRY;
POLO-KINASE; CELL-CYCLE; D-TACC; MITOSIS
AB Pericentriolar material (PCM) mediates the microtubule (MT) nucleation and anchoring activity of centrosomes. A scaffold organized by Centrosomin (Cnn) serves to ensure proper PCM architecture and functional changes in centrosome activity with each cell cycle. Here, we investigate the mechanisms that spatially restrict and temporally coordinate centrosome scaffold formation. Focusing on the mitotic-to-interphase transition in Drosophila melanogaster embryos, we show that the elaboration of the interphase Cnn scaffold defines a major structural rearrangement of the centrosome. We identify an unprecedented role for Pericentrin-like protein (PLP), which localizes to the tips of extended Cnn flares, to maintain robust interphase centrosome activity and promote the formation of interphase MT asters required for normal nuclear spacing, centrosome segregation, and compartmentalization of the syncytial embryo. Our data reveal that Cnn and PLP directly interact at two defined sites to coordinate the cell cycle dependent rearrangement and scaffolding activity of the centrosome to permit normal centrosome organization, cell division, and embryonic viability.
C1 [Lerit, Dorothy A.; Jordan, Holly A.; Fagerstrom, Carey J.; Galletta, Brian J.; Rusan, Nasser M.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA.
[Poulton, John S.; Peifer, Mark] Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA.
RP Rusan, NM (reprint author), NHLBI, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM Nasser@nih.gov
RI Rusan, Nasser/P-3511-2016;
OI Peifer, Mark/0000-0003-1412-3987
FU NIH [R01 GM67236]; Division of Intramural Research at the National
Institutes of Health/NHLBI [1ZIAHL006126]; Lenfant Biomedical
Postdoctoral Fellowship
FX M. Peifer is supported by NIH R01 GM67236, N.M. Rusan is supported by
the Division of Intramural Research at the National Institutes of
Health/NHLBI (1ZIAHL006126), and D.A. Lent is supported by the Lenfant
Biomedical Postdoctoral Fellowship.
NR 84
TC 6
Z9 6
U1 2
U2 7
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA
SN 0021-9525
EI 1540-8140
J9 J CELL BIOL
JI J. Cell Biol.
PD JUL 6
PY 2015
VL 210
IS 1
BP 79
EP 97
DI 10.1083/jcb.201503117
PG 19
WC Cell Biology
SC Cell Biology
GA CM5XZ
UT WOS:000357763600010
PM 26150390
ER
PT J
AU Larion, M
Hansen, AL
Zhang, FL
Bruschweiler-Li, L
Tugarinov, V
Miller, BG
Bruschweiler, R
AF Larion, Mioara
Hansen, Alexandar L.
Zhang, Fengli
Bruschweiler-Li, Lei
Tugarinov, Vitali
Miller, Brian G.
Brueschweiler, Rafael
TI Kinetic Cooperativity in Human Pancreatic Glucokinase Originates from
Millisecond Dynamics of the Small Domain
SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
LA English
DT Article
DE allostery; enzyme catalysis; kinetic cooperativity; NMR spectroscopy;
time-resolved conformational dynamics
ID MOLECULAR-WEIGHT PROTEINS; GERM HEXOKINASE-LI;
NUCLEAR-MAGNETIC-RESONANCE; TIME-SCALE DYNAMICS; NMR-SPECTROSCOPY;
RELAXATION DISPERSION; ENZYME MEMORY; ALLOSTERIC REGULATION; MONOMERIC
ENZYMES; CONFORMATION
AB The hallmark of glucokinase (GCK), which catalyzes the phosphorylation of glucose during glycolysis, is its kinetic cooperativity, whose understanding at atomic detail has remained open since its discovery over 40years ago. Herein, by using kinetic CPMG NMR spectroscopic data for 17 isoleucine side chains distributed over all parts of GCK, we show that the origin of kinetic cooperativity is rooted in intramolecular protein dynamics. Residues of glucose-free GCK located in the small domain displayed distinct exchange behavior involving multiple conformers that are substantially populated (p>17%) with a k(ex)value of 509 +/- 51s(-1), whereas in the glucose-bound form these exchange processes were quenched. This exchange behavior directly competes with the enzymatic turnover rate at physiological glucose concentrations, thereby generating the sigmoidal rate dependence that defines kinetic cooperativity.
C1 [Larion, Mioara; Hansen, Alexandar L.; Bruschweiler-Li, Lei; Brueschweiler, Rafael] Ohio State Univ, Dept Chem & Biochem, Columbus, OH 43210 USA.
[Zhang, Fengli] Natl High Magnet Field Lab, Tallahassee, FL 32306 USA.
[Tugarinov, Vitali] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Miller, Brian G.] Florida State Univ, Dept Chem & Biochem, Tallahassee, FL 32306 USA.
RP Bruschweiler, R (reprint author), Ohio State Univ, Dept Chem & Biochem, 100 West 18th Ave, Columbus, OH 43210 USA.
EM bruschweiler.1@osu.edu
RI Hansen, Alexandar/B-6794-2011
OI Hansen, Alexandar/0000-0003-4474-7141
FU American Heart Association [12POST12040344]; NIH [1R01K081358]; NSF
[MCB-1360966]
FX This research was supported by the American Heart Association (grant
12POST12040344 to M.L.), the NIH (grant 1R01K081358 to B.G.M.), and the
NSF (grant MCB-1360966 to R.B.).
NR 34
TC 5
Z9 5
U1 3
U2 14
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 JUL 6
PY 2015
VL 54
IS 28
BP 8129
EP 8132
DI 10.1002/anie.201501204
PG 4
WC Chemistry, Multidisciplinary
SC Chemistry
GA CL8FO
UT WOS:000357209000016
PM 26013420
ER
PT J
AU Neuschwander-Tetri, BA
Van Natta, ML
Tonascia, J
Brunt, EM
Kleiner, DE
AF Neuschwander-Tetri, Brent A.
Van Natta, Mark L.
Tonascia, James
Brunt, Elizabeth M.
Kleiner, David E.
TI Trials of obeticholic acid for non-alcoholic steatohepatitis Reply
SO LANCET
LA English
DT Letter
C1 [Neuschwander-Tetri, Brent A.] St Louis Univ, St Louis, MO 63103 USA.
[Van Natta, Mark L.; Tonascia, James] Johns Hopkins Univ, Baltimore, MD USA.
[Brunt, Elizabeth M.] Washington Univ, St Louis, MO USA.
[Kleiner, David E.] NCI, Bethesda, MD 20892 USA.
RP Neuschwander-Tetri, BA (reprint author), St Louis Univ, St Louis, MO 63103 USA.
EM tetriba@slu.edu
NR 1
TC 1
Z9 1
U1 0
U2 4
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 JUL 4
PY 2015
VL 386
IS 9988
BP 28
EP 29
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA CM2OA
UT WOS:000357519400022
PM 26169861
ER
PT J
AU Bellanger, AP
Minetos, YD
Albert, N
Shirazi, F
Walsh, TJ
Kontoyiannis, DP
AF Bellanger, A. P.
Minetos, Y. D.
Albert, N.
Shirazi, F.
Walsh, T. J.
Kontoyiannis, D. P.
TI Glucocorticosteroids do not impact directly growth rate and biomass of
Rhizopus arrhizus (syn. R. oryzae) in vitro
SO VIRULENCE
LA English
DT Article
DE corticosteroid; biomass; Rhizopus oryzae
AB Glucocorticoid (GC) use is a common risk factor for invasive fungal infections. This is attributed to the complex dysregulation of immunity caused by GCs. However, studies have demonstrated increased growth with GC exposure for some molds, such as Aspergillus fumigatus and Exserohilum rostratum. No such data exist for Mucorales. Therefore, we investigated the influence of GC exposure on the growth of Rhizopus arrhizus (syn. R. oryzae) in different culture media and in different atmospheres. We measured continuous spore growth using spectrophotometry and biomass variations using XTT assay. We did not observe enhanced growth or biomass variation with any of the GCs regardless of the medium or conditions. These results support the existence of fungus-specific differences in the effect of GCs on fungal biology.
C1 [Bellanger, A. P.; Minetos, Y. D.; Albert, N.; Shirazi, F.; Kontoyiannis, D. P.] Univ Texas MD Anderson Canc Ctr, Infect Dis Dept, Houston, TX 77030 USA.
[Bellanger, A. P.] Univ Franche Comte, Chrono Environm UMR Res Team 6249, F-25030 Besancon, France.
[Bellanger, A. P.] CHU, Parasitol Mycol Dept, F-25030 Besancon, France.
[Walsh, T. J.] NCI, Ctr Canc Res, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA.
RP Kontoyiannis, DP (reprint author), Univ Texas MD Anderson Canc Ctr, Infect Dis Dept, Houston, TX 77030 USA.
EM dkontoyi@mdanderson.org
NR 9
TC 1
Z9 1
U1 0
U2 0
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 2150-5594
EI 2150-5608
J9 VIRULENCE
JI Virulence
PD JUL 4
PY 2015
VL 6
IS 5
BP 441
EP 443
DI 10.1080/21505594.2015.1039762
PG 3
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA CM4IZ
UT WOS:000357649400010
PM 25942104
ER
PT J
AU Olaku, OO
Ojukwu, MO
Zia, FZ
White, JD
AF Olaku, Oluwadamilola O.
Ojukwu, Mary O.
Zia, Farah Z.
White, Jeffrey D.
TI The Role of Grape Seed Extract in the Treatment of Chemo/Radiotherapy
Induced Toxicity: A Systematic Review of Preclinical Studies
SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL
LA English
DT Article
ID DOXORUBICIN-INDUCED CARDIOTOXICITY; INDUCED OXIDATIVE STRESS; PRODUCE
SIGNIFICANT ATTENUATION; PROANTHOCYANIDIN EXTRACT; VITIS-VINIFERA;
LIPID-PEROXIDATION; INTESTINAL MUCOSITIS; ANTIOXIDANT ACTIVITY;
CELLULAR-RESPONSES; TOPOISOMERASE-II
AB Grapes are one of the most consumed fruits in the world and are rich in polyphenols. Grape seed proanthocyanidins (GSP) have demonstrated chemopreventive and/or chemotherapeutic effects in various cancer cell cultures and animal models. The clinical efficacy of chemotherapy is often limited by its adverse effects. Several studies show that reactive oxygen species mediate the cardiotoxicity and neurotoxicity induced by various cancer chemotherapeutic agents. This implies that concomitant administration of antioxidants may prevent these adverse effects. The review was carried out in accordance with the PRISMA guidelines. An electronic search strategy in Medline and Embase databases was conducted. Of the 41 studies reviewed, 27 studied GSP while the remainder (14) studied grape seed or skin extracts (GSE). All the studies were published in English, except 2 in Chinese. A significant percentage (34%) of the studies we reviewed assessed the effect of GSE or GSP on cardiotoxicity induced by chemotherapy. Doxorubicin was the most common chemotherapeutic drug studied followed by cisplatin. Research studies that assessed the effect of GSE or GSP on radiation treatment accounted for 22% of the articles reviewed. GSE/GSP ameliorates some of the cytotoxic effects on normal cells/tissues induced by chemo/radiotherapy.
C1 [Olaku, Oluwadamilola O.; Ojukwu, Mary O.; Zia, Farah Z.; White, Jeffrey D.] NCI, Off Canc Complementary & Alternat Med, Bethesda, MD 20892 USA.
[Olaku, Oluwadamilola O.] Kelly Serv, Rockville, MD USA.
RP Olaku, OO (reprint author), NCI, Off Canc Complementary & Alternat Med, 9609 Med Ctr Dr,5-W622,MSC 9743, Bethesda, MD 20892 USA.
EM Olakuo@mail.nih.gov
FU National Cancer Institute (NCI)
FX Funding for this article was provided by the National Cancer Institute
(NCI). The NCI did not participate in the design, analysis,
interpretation of data, and writing of article.
NR 93
TC 6
Z9 6
U1 1
U2 25
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND
SN 0163-5581
EI 1532-7914
J9 NUTR CANCER
JI Nutr. Cancer
PD JUL 4
PY 2015
VL 67
IS 5
BP 730
EP 740
DI 10.1080/01635581.2015.1029639
PG 11
WC Oncology; Nutrition & Dietetics
SC Oncology; Nutrition & Dietetics
GA CL5SJ
UT WOS:000357020600003
PM 25880972
ER
PT J
AU Nonaka, M
Matsuda, N
Kono, T
Fujio, M
Scahill, L
Kano, Y
AF Nonaka, Maiko
Matsuda, Natsumi
Kono, Toshiaki
Fujio, Miyuki
Scahill, Lawrence
Kano, Yukiko
TI Preliminary Study of Behavioral Therapy for Tourette Syndrome Patients
in Japan
SO CHILDRENS HEALTH CARE
LA English
DT Article
ID EUROPEAN CLINICAL GUIDELINES; QUALITY-OF-LIFE; PSYCHOSOCIAL
INTERVENTIONS; TIC DISORDERS; CHILDREN; ADULTS; SEVERITY; TRIAL; SCALE
AB Tourette syndrome (TS) is a chronic neurobehavioral disorder of childhood characterized by motor and vocal tics. The authors aimed to show the feasibility of Comprehensive Behavioral Intervention for Tics (CBIT) for pediatric Tourette syndrome patients in Japan. Seven subjects (age 9 to 20 years) were treated with CBIT. Changes in tic severity, premonitory urges, and subjective distress associated with tics were investigated over the course of 9 treatment sessions. Results showed that significant decrease of tic severity and improvement of their subjective distress of tics. However, the subjective distress from coprolalia was difficult to change. The treatment for outburst of coprolalia should be investigated more.
C1 [Nonaka, Maiko; Fujio, Miyuki] Univ Tokyo, Grad Sch Educ, Dept Clin Psychol, Tokyo 1138655, Japan.
[Nonaka, Maiko; Matsuda, Natsumi; Kono, Toshiaki; Fujio, Miyuki; Kano, Yukiko] Tokyo Univ Hosp, Dept Child Psychiat, Tokyo 113, Japan.
[Kono, Toshiaki] NIMH, Dept Forens Psychiat, Natl Ctr Neurol & Psychiat, Bethesda, MD 20892 USA.
[Scahill, Lawrence] Emory Univ, Sch Med, Atlanta, GA USA.
[Scahill, Lawrence] Marcus Autism Ctr, Atlanta, GA USA.
[Kano, Yukiko] Univ Tokyo, Grad Sch Med, Dept Child Neuropsychiat, Tokyo 1138655, Japan.
RP Kano, Y (reprint author), Univ Tokyo, Grad Sch Med, Dept Child Neuropsychiat, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan.
EM kano-tky@umin.ac.jp
FU Shire; Roche Pharmaceutuicals; Tourette Syndrome Association
FX The present study was supported by a Grant-in-Aid for Japan Society for
the Promotion of Science (JSPS) Fellows. Dr. Scahill has received
research support from Shire and Roche Pharmaceutuicals. He has served as
a consultant to Coronado, MedAdvante, Roche, Bracket, Neuren. He has
also received book royalties from Oxford and speaker fees from the
Tourette Syndrome Association.
NR 30
TC 0
Z9 0
U1 2
U2 3
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND
SN 0273-9615
EI 1532-6888
J9 CHILD HEALTH CARE
JI Child. Health Care
PD JUL 3
PY 2015
VL 44
IS 3
SI SI
BP 293
EP 306
DI 10.1080/02739615.2014.979922
PG 14
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CW4HF
UT WOS:000364951400008
ER
PT J
AU Chang, K
Yoon, S
Sheth, N
Seidel, M
Antalek, M
Ahad, J
Darlington, T
Ikeda, A
Kato, GJ
Ackerman, H
Gorbach, AM
AF Chang, Ken
Yoon, Stephen
Sheth, Niral
Seidel, Miles
Antalek, Matthew
Ahad, James
Darlington, Thomas
Ikeda, Allison
Kato, Gregory J.
Ackerman, Hans
Gorbach, Alexander M.
TI Rapid vs. delayed infrared responses after ischemia reveal recruitment
of different vascular beds
SO QUANTITATIVE INFRARED THERMOGRAPHY JOURNAL
LA English
DT Article
DE infrared imaging; post-occlusion reactive hyperemia; angiosome;
peripheral vasculature; skin microcirculation; k-means; thermography;
image processing; temperature regulation; precision placement of sensors
ID BLOOD-FLOW; SKIN
AB Continuous infrared imaging revealed transient changes in forearm temperature during arterial occlusion, reperfusion, and recovery in a healthy subject group. Processing the imaging data with the k-means algorithm further revealed reactive vascular sites in the skin with rapid or delayed temperature amplification. The observed temporal and spatial diversity of blood-flow-derived forearm temperature allow consideration of thermal-imaging guided placement of skin sensors to achieve enhanced sensitivity in monitoring of skin hemodynamics.
C1 [Chang, Ken; Yoon, Stephen; Sheth, Niral; Seidel, Miles; Antalek, Matthew; Ahad, James; Darlington, Thomas; Gorbach, Alexander M.] Natl Inst Biomed Imaging & Bioengn, Infrared Imaging & Thermometry Unit, NIH, Bethesda, MD 20892 USA.
[Ikeda, Allison; Ackerman, Hans] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
[Kato, Gregory J.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Kato, Gregory J.] Univ Pittsburgh, Med Ctr, Div Hematol Oncol, Vasc Med Inst, Pittsburgh, PA USA.
RP Gorbach, AM (reprint author), Natl Inst Biomed Imaging & Bioengn, Infrared Imaging & Thermometry Unit, NIH, Bethesda, MD 20892 USA.
EM gorbacha@mail.nih.gov
OI Kato, Gregory/0000-0003-4465-3217
FU National Heart, Lung, and Blood Institute, National Institutes of
Health; National Institute of Allergy and Infectious Diseases, National
Institutes of Health; National Institute of Biomedical Imaging and
Bioengineering, National Institutes of Health
FX The authors acknowledge the technical contributions of N. Malik, J.
Maivelett, J. Meyer, T. Anabere, and L. Mendelsohn, the nursing support
of the NIH Clinical Center, and protocol management by M. Hall, S.
Housel, and D. Smith. We also acknowledge Dr H. Eden for editing the
manuscript. This research was supported by the Intramural Research
Programs of the National Heart, Lung, and Blood Institute, the National
Institute of Allergy and Infectious Diseases, and the National Institute
of Biomedical Imaging and Bioengineering, National Institutes of Health.
NR 11
TC 0
Z9 0
U1 0
U2 2
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1768-6733
EI 2116-7176
J9 QUANT INFR THERM J
JI Quant. Infrared Thermogr. J.
PD JUL 3
PY 2015
VL 12
IS 2
BP 173
EP 183
DI 10.1080/17686733.2015.1046677
PG 11
WC Instruments & Instrumentation; Materials Science, Characterization &
Testing; Physics, Applied
SC Instruments & Instrumentation; Materials Science; Physics
GA CS5GK
UT WOS:000362105500005
PM 26435756
ER
PT J
AU Lessey-Morillon, EC
Roberts, DD
AF Lessey-Morillon, Elizabeth C.
Roberts, David D.
TI Thrombospondin-1 An Extracellular Message Delivered by Macrophages That
Promotes Aortic Aneurysms
SO CIRCULATION RESEARCH
LA English
DT Editorial Material
DE Editorials; antigens; CD47; aortic aneurysm; bone marrow; cell movement;
inflammation
ID MODELS; MOUSE
C1 [Lessey-Morillon, Elizabeth C.; Roberts, David D.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Roberts, DD (reprint author), NCI, NIH, Pathol Lab, Bldg 10,Room 2A33,10 Ctr Dr MSC1500, Bethesda, MD 20892 USA.
EM droberts@helix.nih.gov
RI Roberts, David/A-9699-2008
OI Roberts, David/0000-0002-2481-2981
FU Intramural NIH HHS [ZIA SC009172-26]
NR 15
TC 0
Z9 0
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7330
EI 1524-4571
J9 CIRC RES
JI Circ.Res.
PD JUL 3
PY 2015
VL 117
IS 2
BP 113
EP 115
DI 10.1161/CIRCRESAHA.117.306815
PG 3
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA CM9AW
UT WOS:000357998500003
PM 26139855
ER
PT J
AU Berkman, BE
Hull, SC
Biesecker, LG
AF Berkman, Benjamin E.
Hull, Sara Chandros
Biesecker, Leslie G.
TI Scrutinizing the Right Not to Know
SO AMERICAN JOURNAL OF BIOETHICS
LA English
DT Editorial Material
C1 [Berkman, Benjamin E.; Hull, Sara Chandros; Biesecker, Leslie G.] NIH, Bethesda, MD 20892 USA.
RP Berkman, BE (reprint author), NIH, Dept Bioeth, Bldg 10 Room 1C118,10 Ctr Dr,MSC 1156, Bethesda, MD 20892 USA.
EM berkmanbe@mail.nih.gov
NR 7
TC 2
Z9 2
U1 0
U2 2
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND
SN 1526-5161
EI 1536-0075
J9 AM J BIOETHICS
JI Am. J. Bioeth.
PD JUL 3
PY 2015
VL 15
IS 7
BP 17
EP 19
DI 10.1080/15265161.2015.1039733
PG 3
WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Medical Ethics; Social Issues;
Biomedical Social Sciences
GA CM2CO
UT WOS:000357487600004
PM 26147256
ER
PT J
AU Nomme, J
Antanasijevic, A
Caffrey, M
Van Itallie, CM
Anderson, JM
Fanning, AS
Lavie, A
AF Nomme, Julian
Antanasijevic, Aleksandar
Caffrey, Michael
Van Itallie, Christina M.
Anderson, James M.
Fanning, Alan S.
Lavie, Arnon
TI Structural Basis of a Key Factor Regulating the Affinity between the
Zonula Occludens First PDZ Domain and Claudins
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID TIGHT-JUNCTION; EXTRACELLULAR DOMAINS; EPITHELIAL-CELLS; PROTEIN ZO-1;
RECOGNITION; SPECIFICITY; PHOSPHORYLATION; DETERMINANTS; DIMERIZATION;
BARRIER
AB The molecular seal between epithelial cells, called the tight junction (TJ), is built by several membrane proteins, with claudins playing the most prominent role. The scaffold proteins of the zonula occludens family are required for the correct localization of claudins and hence formation of the TJ. The intracellular C terminus of claudins binds to the N-terminal PDZ domain of zonula occludens proteins (PDZ1). Of the 23 identified human claudin proteins, nine possess a tyrosine at the -6 position. Here we show that the claudin affinity for PDZ1 is dependent on the presence or absence of this tyrosine and that the affinity is reduced if the tyrosine is modified by phosphorylation. The PDZ1 beta 2-beta 3 loop undergoes a significant conformational change to accommodate this tyrosine. Cell culture experiments support a regulatory role for this tyrosine. Plasticity has been recognized as a critical property of TJs that allow cell remodeling and migration. Our work provides a molecular framework for how TJ plasticity may be regulated.
C1 [Nomme, Julian; Antanasijevic, Aleksandar; Caffrey, Michael; Lavie, Arnon] Univ Illinois, Dept Biochem & Mol Genet, Chicago, IL 60607 USA.
[Van Itallie, Christina M.; Anderson, James M.] NHLBI, Lab Tight Junct Struct & Funct, NIH, Bethesda, MD 20892 USA.
[Fanning, Alan S.] Univ N Carolina, Dept Cell Biol & Physiol, Chapel Hill, NC 27599 USA.
RP Lavie, A (reprint author), Univ Illinois, Dept Biochem & Mol Genet, Chicago, IL 60607 USA.
EM lavie@uic.edu
RI Regan, Clinton/E-6250-2012
FU National Institutes of Health [DK61397, AI101676]; Division of
Intramural Research, National Institutes of Health
FX This work was supported, in whole or in part, by National Institutes of
Health Grants DK61397 (to A. S. F. and A. L.) and AI101676 (to M. C.).
The authors declare that they have no conflicts of interest with the
contents of this article.; Supported by the Division of Intramural
Research, National Institutes of Health.
NR 35
TC 4
Z9 4
U1 0
U2 4
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 3
PY 2015
VL 290
IS 27
BP 16595
EP 16606
DI 10.1074/jbc.M115.646695
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CM3HN
UT WOS:000357572800012
PM 26023235
ER
PT J
AU Behl, M
Stout, MD
Herbert, RA
Dill, JA
Baker, GL
Hayden, BK
Roycroft, JH
Bucher, JR
Hooth, MJ
AF Behl, Mamta
Stout, Matthew D.
Herbert, Ronald A.
Dill, Jeffrey A.
Baker, Gregory L.
Hayden, Barry K.
Roycroft, Joseph H.
Bucher, John R.
Hooth, Michelle J.
TI Comparative toxicity and carcinogenicity of soluble and insoluble cobalt
compounds
SO TOXICOLOGY
LA English
DT Article
DE Cobalt; Cancer; Toxicity; Rats; Mice
ID TUNGSTEN CARBIDE; RAT LUNG; INHALATION; PARTICLES; LESIONS;
GENOTOXICITY; TOXICOLOGY; CLEARANCE; MORTALITY; MECHANISM
AB Occupational exposure to cobalt is of widespread concern due to its use in a variety of industrial processes and the occurrence of occupational disease. Due to the lack of toxicity and carcinogenicity data following exposure to cobalt, and questions regarding bioavailability following exposure to different forms of cobalt, the NTP conducted two chronic inhalation exposure studies in rats and mice, one on soluble cobalt sulfate heptahydrate, and a more recent study on insoluble cobalt metal. Herein, we compare and contrast the toxicity profiles following whole-body inhalation exposures to these two forms of cobalt.
In general, both forms were genotoxic in the Salmonella T98 strain in the absence of effects on micronuclei. The major sites of toxicity and carcinogenicity in both chronic inhalation studies were the respiratory tract in rats and mice, and the adrenal gland in rats. In addition, there were distinct sites of toxicity and carcinogenicity noted following exposure to cobalt metal. In rats, carcinogenicity was observed in the blood, and pancreas, and toxicity was observed in the testes of rats and mice. Taken together, these findings suggest that both forms of cobalt, soluble and insoluble, appear to be multi-site rodent carcinogens following inhalation exposure. Published by Elsevier Ireland Ltd.
C1 [Behl, Mamta; Stout, Matthew D.; Herbert, Ronald A.; Roycroft, Joseph H.; Bucher, John R.; Hooth, Michelle J.] NIEHS, Div Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
[Dill, Jeffrey A.; Baker, Gregory L.; Hayden, Barry K.] Battelle Mem Inst, Columbus, OH 43201 USA.
RP Behl, M (reprint author), NIEHS, Div Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA.
EM behlmv@niehs.nih.gov
NR 66
TC 7
Z9 7
U1 2
U2 13
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0300-483X
J9 TOXICOLOGY
JI Toxicology
PD JUL 3
PY 2015
VL 333
BP 195
EP 205
DI 10.1016/j.tox.2015.04.008
PG 11
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA CL8MG
UT WOS:000357228200019
PM 25896363
ER
PT J
AU Godino, A
Jayanthi, S
Cadet, JL
AF Godino, Arthur
Jayanthi, Subramaniam
Cadet, Jean Lud
TI Epigenetic landscape of amphetamine and methamphetamine addiction in
rodents
SO EPIGENETICS
LA English
DT Article
DE amphetamine; DNA methylation; histone acetylation; histone methylation;
methamphetamine
ID INDUCED BEHAVIORAL SENSITIZATION; HISTONE DEACETYLASE INHIBITORS;
DELTA-FOSB; NUCLEUS-ACCUMBENS; NEUROTROPHIC FACTOR; LOCOMOTOR-ACTIVITY;
NEURAL PLASTICITY; SODIUM-BUTYRATE; GENE-EXPRESSION; ANIMAL-MODEL
AB Amphetamine and methamphetamine addiction is described by specific behavioral alterations, suggesting long-lasting changes in gene and protein expression within specific brain subregions involved in the reward circuitry. Given the persistence of the addiction phenotype at both behavioral and transcriptional levels, several studies have been conducted to elucidate the epigenetic landscape associated with persistent effects of drug use on the mammalian brain. This review discusses recent advances in our comprehension of epigenetic mechanisms underlying amphetamine- or methamphetamine-induced behavioral, transcriptional, and synaptic plasticity. Accumulating evidence demonstrated that drug exposure induces major epigenetic modificationshistone acetylation and methylation, DNA methylationin a very complex manner. In rare instances, however, the regulation of a specific target gene can be correlated to both epigenetic alterations and behavioral abnormalities. Work is now needed to clarify and validate an epigenetic model of addiction to amphetamines. Investigations that include genome-wide approaches will accelerate the speed of discovery in the field of addiction.
C1 [Godino, Arthur] Ecole Normale Super Lyon, Dept Biol, F-69364 Lyon, France.
[Jayanthi, Subramaniam; Cadet, Jean Lud] NIDA, Mol Neuropsychiat Res Branch, NIH, Intramural Res Program, Baltimore, MD 21224 USA.
RP Cadet, JL (reprint author), NIDA, Mol Neuropsychiat Res Branch, NIH, Intramural Res Program, Baltimore, MD 21224 USA.
EM jcadet@intra.nida.nih.gov
FU US Department of Health and Human Services/National Institutes of
Health/National Institute on Drug Abuse
FX This work was supported by funds of the Intramural Research Program of
the US Department of Health and Human Services/National Institutes of
Health/National Institute on Drug Abuse.
NR 57
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Z9 14
U1 3
U2 15
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1559-2294
EI 1559-2308
J9 EPIGENETICS-US
JI Epigenetics
PD JUL 3
PY 2015
VL 10
IS 7
BP 574
EP 580
DI 10.1080/15592294.2015.1055441
PG 7
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA CL4WM
UT WOS:000356957200002
PM 26023847
ER
PT J
AU Rutten, LJF
Agunwamba, AA
Beckjord, E
Hesse, BW
Moser, RP
Arora, NK
AF Rutten, Lila J. Finney
Agunwamba, Amenah A.
Beckjord, Ellen
Hesse, Bradford W.
Moser, Richard P.
Arora, Neeraj K.
TI The Relation Between Having a Usual Source of Care and Ratings of Care
Quality: Does Patient-Centered Communication Play a Role?
SO JOURNAL OF HEALTH COMMUNICATION
LA English
DT Article
ID MEDICAL HOME; HEALTH-CARE; INSURANCE-COVERAGE; CANCER-PATIENTS;
INFORMATION; OUTCOMES; DISPARITIES; SERVICES; RECEIPT; NEEDS
AB Having a usual source of health care has been consistently associated with greater use of preventive services, decreased use of emergency services, and with patients' ratings of quality and satisfaction with care. Ongoing patient-provider relationships may be, in part, fostered by patient-centered communication. Growing evidence demonstrates that positive patient-centered communication improves adherence to treatment recommendations, management of chronic disease, quality of life, and disease-related outcomes. We aimed to determine how patient-centered communication between patients and physicians might mediate the relation between having a source of usual care and ratings of health care quality. We analyzed data from Cycle 1 of the fourth iteration of the Health Information National Trends Survey. Data were collected through mailed questionnaire in October 2011 through February 2012 (N=3,959). Overall, individuals with a usual source of care reported more patient-centered communication experiences and had higher ratings of quality of care. Parameter estimates for each pathway in the mediation model were estimated through regression analysis. Results confirm the importance of patient-centered communication in shaping patients' perceptions of the quality of their care, accounting for a significant portion of the observed relation between having a usual source of care and ratings of quality.
C1 [Rutten, Lila J. Finney; Agunwamba, Amenah A.] Mayo Clin, Robert D & Patricia E Kern Ctr Sci Healthcare Del, Rochester, MN 55905 USA.
[Beckjord, Ellen] Univ Pittsburgh, Med Ctr, Hlth Plan, Insurance Serv Div, Pittsburgh, PA USA.
[Hesse, Bradford W.; Moser, Richard P.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Arora, Neeraj K.] Patient Ctr Outcomes Res Inst, Washington, DC USA.
RP Rutten, LJF (reprint author), Mayo Clin, Div Epidemiol, Dept Hlth Sci Res, 200 First St SW, Rochester, MN 55905 USA.
EM rutten.lila@mayo.edu
OI Hesse, Bradford/0000-0003-1142-1161
NR 37
TC 5
Z9 5
U1 1
U2 9
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1081-0730
EI 1087-0415
J9 J HEALTH COMMUN
JI J. Health Commun.
PD JUL 3
PY 2015
VL 20
IS 7
BP 759
EP 765
DI 10.1080/10810730.2015.1018592
PG 7
WC Communication; Information Science & Library Science
SC Communication; Information Science & Library Science
GA CL6QS
UT WOS:000357092700003
ER
PT J
AU Martin-Biggers, J
Beluska, K
Quick, V
Tursi, M
Byrd-Bredbenner, C
AF Martin-Biggers, Jennifer
Beluska, Katrina
Quick, Virginia
Tursi, Mary
Byrd-Bredbenner, Carol
TI Cover Lines Using Positive, Urgent, Unique Language Entice Moms to Read
Health Communications
SO JOURNAL OF HEALTH COMMUNICATION
LA English
DT Article
ID FOOD ADVERTISEMENTS; WOMENS MAGAZINES; UNITED-STATES; MESSAGES;
STRATEGIES; NUTRITION
AB Crafting messages that capture consumer interest is a frequent challenge of health communicators. A better understanding of the techniques magazine editors use to create cover lines may aid health communicators in their efforts to arouse interest in their communiques. This study (a) content-analyzed magazine cover lines, (b) used content analysis findings to create health-related cover lines, and (c) assessed the degree to which the health-related cover lines fostered motivation to read the health communication. Cover lines (N=867) from 11 magazines published in 2012 frequently read by mothers of young children used a variety of themes, with those focusing on informative/how-to, control/improve, and unique/special being most common. Health communication experts used key descriptor terms corresponding to each theme and wrote 310 cover lines for topics focusing on childhood obesity prevention strategies. Unpaired t tests revealed that mothers of young children (N=77) reported they were significantly (p<.05) more motivated to read a short, health-related magazine article when cover lines had a happiness/fun, unique/special, or quick/urgency theme and were significantly less motivated to read when cover lines used a control/improve theme. Study findings may help health communicators create cover lines that better attract reader attention.
C1 [Martin-Biggers, Jennifer; Beluska, Katrina; Tursi, Mary; Byrd-Bredbenner, Carol] Rutgers State Univ, New Brunswick, NJ 08901 USA.
[Quick, Virginia] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Byrd-Bredbenner, C (reprint author), Rutgers State Univ, 26 Nichol Ave, New Brunswick, NJ 08901 USA.
EM bredbenner@aesop.rutgers.edu
FU United States Department of Agriculture, National Institute of Food and
Agriculture [2011-68001-30170]; National Institutes of Health, Eunice
Kennedy Shriver National Institute of Child Health and Human Development
FX This research was supported by the United States Department of
Agriculture, National Institute of Food and Agriculture, Grant Number
2011-68001-30170, and was supported in part by the intramural research
program of the National Institutes of Health, Eunice Kennedy Shriver
National Institute of Child Health and Human Development.
NR 38
TC 2
Z9 2
U1 4
U2 8
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1081-0730
EI 1087-0415
J9 J HEALTH COMMUN
JI J. Health Commun.
PD JUL 3
PY 2015
VL 20
IS 7
BP 766
EP 772
DI 10.1080/10810730.2015.1018581
PG 7
WC Communication; Information Science & Library Science
SC Communication; Information Science & Library Science
GA CL6QS
UT WOS:000357092700004
PM 25928099
ER
PT J
AU Prestin, A
Vieux, SN
Chou, WYS
AF Prestin, Abby
Vieux, Sana N.
Chou, Wen-ying Sylvia
TI Is Online Health Activity Alive and Well or Flat lining? Findings From
10 Years of the Health Information National Trends Survey
SO JOURNAL OF HEALTH COMMUNICATION
LA English
DT Article
ID DIGITAL DIVIDE; CARE PROVIDERS; SUPPORT GROUPS; UNITED-STATES; INTERNET;
RACE; COMMUNICATION; PHYSICIAN; SEEKING; ACCESS
AB The Internet increasingly enables diverse health communication activities, from information seeking to social media interaction. Up-to-date reporting is needed to document the national prevalence, trends, and user profiles of online health activities so that these technologies can be best used in health communication efforts. This study identifies prevalence, trend, and factors associated with seeking health information, e-mailing health care providers, and using social media for health purposes. Four iterations of HINTS survey data, collected in 2003, 2005, 2008, and 2012, were analyzed to assess population-level trends over the last decade, and current prevalence of Internet-based health communication activities. Sociodemographic and health correlates were explored through weighted logistic regression modeling. Findings demonstrated that Internet use has steadily increased, with 78% of U.S. adults online in 2012; however several digital divide factorsamong them education, age, and race/ethnicitystill predict access. Once online, 70% of adults use the Internet as their first source for health information, and while 19% have e-mailed health care providers, engagement in health communication on social media is still relatively low. Distinct user profiles characterize each type of communication, with age, population density, and gender emerging as important predictors across online health activities. These findings have important implications for health communication research and practice.
C1 [Prestin, Abby; Vieux, Sana N.; Chou, Wen-ying Sylvia] NCI, Div Canc Control & Populat Sci, NIH, Rockville, MD 20892 USA.
[Prestin, Abby] US FDA, Off Sci, Ctr Tobacco Prod, Rockville, MD 20857 USA.
RP Chou, WYS (reprint author), NCI, Hlth Commun & Informat Res Branch, Div Canc Control & Populat Sci, 9609 Med Ctr Dr 3E614, Rockville, MD 20892 USA.
EM chouws@mail.nih.gov
NR 43
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Z9 13
U1 8
U2 25
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1081-0730
EI 1087-0415
J9 J HEALTH COMMUN
JI J. Health Commun.
PD JUL 3
PY 2015
VL 20
IS 7
BP 790
EP 798
DI 10.1080/10810730.2015.1018590
PG 9
WC Communication; Information Science & Library Science
SC Communication; Information Science & Library Science
GA CL6QS
UT WOS:000357092700007
PM 26042588
ER
PT J
AU Gres, AT
Kirby, KA
KewalRamani, VN
Tanner, JJ
Pornillos, O
Sarafianos, SG
AF Gres, Anna T.
Kirby, Karen A.
KewalRamani, Vineet N.
Tanner, John J.
Pornillos, Owen
Sarafianos, Stefan G.
TI X-ray crystal structures of native HIV-1 capsid protein reveal
conformational variability
SO SCIENCE
LA English
DT Article
ID ASSEMBLY INHIBITOR; DIMERIZATION DOMAIN; NUCLEAR ENTRY; BINDING;
INFECTION; DYNAMICS; COMPLEX; MODEL; CPSF6
AB The detailed molecular interactions between native HIV-1 capsid protein (CA) hexamers that shield the viral genome and proteins have been elusive. We report crystal structures describing interactions between CA monomers related by sixfold symmetry within hexamers (intrahexamer) and threefold and twofold symmetry between neighboring hexamers (interhexamer). The structures describe how CA builds hexagonal lattices, the foundation of mature capsids. Lattice structure depends on an adaptable hydration layer modulating interactions among CA molecules. Disruption of this layer alters interhexamer interfaces, highlighting an inherent structural variability. A CA-targeting antiviral affects capsid stability by binding across CA molecules and subtly altering interhexamer interfaces remote to the ligand-binding site. Inherent structural plasticity, hydration layer rearrangement, and effector binding affect capsid stability and have functional implications for the retroviral life cycle.
C1 [Gres, Anna T.; Kirby, Karen A.; Sarafianos, Stefan G.] Univ Missouri, Christopher S Bond Life Sci Ctr, Columbia, MO 65211 USA.
[Gres, Anna T.; Tanner, John J.] Univ Missouri, Dept Chem, Columbia, MO 65211 USA.
[Kirby, Karen A.; Sarafianos, Stefan G.] Univ Missouri, Dept Mol Microbiol & Immunol, Sch Med, Columbia, MO 65211 USA.
[KewalRamani, Vineet N.] NCI, Basic Res Lab, Ctr Canc Res, Frederick, MD 21702 USA.
[Tanner, John J.; Sarafianos, Stefan G.] Univ Missouri, Dept Biochem, Columbia, MO 65211 USA.
[Pornillos, Owen] Univ Virginia, Sch Med, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA.
RP Sarafianos, SG (reprint author), Univ Missouri, Christopher S Bond Life Sci Ctr, Columbia, MO 65211 USA.
EM sarafianoss@missouri.edu
OI Sarafianos, Stefan G/0000-0002-5840-154X; Kirby, Karen
A./0000-0003-2468-4796
FU Office of Science, Office of Basic Energy Sciences, of the U.S.
Department of Energy [DE-AC02-05CH11231]; NIH [AI112417, AI120860,
GM103368, AI076119, AI099284, AI100890, GM066087]
FX We thank J. Nix of Advanced Light Source (ALS) beamline 4.2.2 for
assistance with data collection. ALS is supported by the Director,
Office of Science, Office of Basic Energy Sciences, of the U.S.
Department of Energy under contract DE-AC02-05CH11231. single-wavelength
anomalous diffraction phasing and initial model building were carried
out at the workshop entitled "CCP4/APS School in Macromolecular
Crystallography: From Data Collection to Structure Refinement and
Beyond" at the Argonne National Laboratory in June 2014
(www.ccp4.ac.uk/schools/APS-2014/index.php). We also thank all the
lecturers of the workshop and the staff of Advanced Photon Source Sector
23 (GM/CA-CAT) for helpful discussions regarding data collection,
processing, refinement, and validation strategies. We also thank C. Tang
for providing a CA-expressing plasmid. The data presented in this
manuscript are tabulated in the main paper and in the supplementary
materials. Final coordinates and structure factors have been deposited
in the Protein Data Bank (PDB) and are available under accession codes
4XFX (CA), 4XFY (dCA), and 4XFZ (CAPF74). This work was supported in
whole or in part by NIH grants AI112417, AI120860, GM103368, AI076119,
AI099284, and AI100890 (S.G.S.) and GM066087 (O.P.).
NR 34
TC 39
Z9 40
U1 4
U2 37
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 JUL 3
PY 2015
VL 349
IS 6243
BP 99
EP 103
DI 10.1126/science.aaa5936
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CL9FG
UT WOS:000357280800068
PM 26044298
ER
PT J
AU Yao, Y
Fujimoto, LM
Hirshman, N
Bobkov, AA
Antignani, A
Youle, RJ
Marassi, FM
AF Yao, Yong
Fujimoto, Lynn M.
Hirshman, Nathan
Bobkov, Andrey A.
Antignani, Antonella
Youle, Richard J.
Marassi, Francesca M.
TI Conformation of BCL-XL upon Membrane Integration
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
ID PHOSPHOLIPID-BILAYER NANODISCS; PROGRAMMED CELL-DEATH; C-TERMINAL HELIX;
FAMILY PROTEINS; PEPTIDE COMPLEX; LIGAND-BINDING; BCL-X(L) FORMS; BAX;
MITOCHONDRIA; DIMERIZATION
AB BCL-XL is an anti-apoptotic BCL-2 family protein found both in the cytosol and bound to intracellular membranes. Structural studies of BCL-XL have advanced by deleting its hydrophobic C-terminus and adding detergents to enhance solubility. However, since the C-terminus is essential for function and detergents strongly affect structure and activity, the molecular mechanisms controlling intracellular localization and cytoprotective activity are incompletely understood. Here we describe the conformations and ligand binding activities of water-soluble and membrane-bound BCL-XL, with its complete C-terminus, in detergent-free environments. We show that the C-terminus interacts with a conserved surface groove in the water-soluble state of the protein and inserts across the phospholipid bilayer in the membrane-bound state. Contrary to current models, membrane binding does not induce a conformational change in the soluble domain and both states bind a known ligand with affinities that are modulated by the specific state of the protein. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Yao, Yong; Fujimoto, Lynn M.; Hirshman, Nathan; Bobkov, Andrey A.; Marassi, Francesca M.] Sanford Burnham Med Res Inst, La Jolla, CA 92037 USA.
[Antignani, Antonella; Youle, Richard J.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
RP Marassi, FM (reprint author), Sanford Burnham Med Res Inst, 10901 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM fmarassi@sbmri.org
FU National Institutes of Health [R01 CA179087, R01 GM100265, P41EB002031,
P30 CA030199]
FX This work was supported by grants (R01 CA179087, R01 GM100265,
P41EB002031 and P30 CA030199) from the National Institutes of Health.
NR 38
TC 12
Z9 12
U1 2
U2 14
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
EI 1089-8638
J9 J MOL BIOL
JI J. Mol. Biol.
PD JUL 3
PY 2015
VL 427
IS 13
BP 2262
EP 2270
DI 10.1016/j.jmb.2015.02.019
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CL0OO
UT WOS:000356642200002
PM 25731750
ER
PT J
AU Stenehjem, JS
Friesen, MC
Eggen, T
Kjaerheim, K
Bratveit, M
Grimsrud, TK
AF Stenehjem, Jo S.
Friesen, Melissa C.
Eggen, Tone
Kjaerheim, Kristina
Bratveit, Magne
Grimsrud, Tom K.
TI Self-reported Occupational Exposures Relevant for Cancer among 28,000
Offshore Oil Industry Workers Employed between 1965 and 1999
SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HYGIENE
LA English
DT Article
DE petroleum industry; inhalation; carcinogens; health hazards; skin
contact
ID PETROLEUM-INDUSTRY; NORWAY; CARCINOGENS
AB The objective of this study was to examine self-reported frequency of occupational exposure reported by 28,000 Norwegian offshore oil workers in a 1998 survey. Predictors of self-reported exposure frequency were identified to aid future refinements of an expert-based job-exposure-time matrix (JEM). We focus here on reported frequencies for skin contact with oil and diesel; exposure to oil vapor from shaker, to exhaust fumes, vapor from mixing chemicals used for drilling, natural gas, chemicals used for water injection and processing, and to solvent vapor. Exposure frequency was reported by participants as the exposed proportion of the work shift, defined by six categories, in their current or last position offshore (between 1965 and 1999). Binary Poisson regression models with robust variance were used to examine the probabilities of reporting frequent exposure (>= 1/4 vs. < 1/4 of work shift) according to main activity, time period, supervisory position, type of company, type of installation, work schedule, and education. Holding a non-supervisory position, working shifts, being employed in the early period of the offshore industry, and having only compulsory education increased the probability of reporting frequent exposure. The identified predictors and group-level patterns may aid future refinement of the JEM previously developed for the present cohort.
C1 [Stenehjem, Jo S.; Eggen, Tone; Kjaerheim, Kristina; Grimsrud, Tom K.] Canc Registry Norway, Dept Res, N-0304 Oslo, Norway.
[Friesen, Melissa C.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Bratveit, Magne] Univ Bergen, Dept Global Publ Hlth & Primary Care, Bergen, Norway.
RP Grimsrud, TK (reprint author), Canc Registry Norway, POB 5313 Majorstuen, N-0304 Oslo, Norway.
EM tom.k.grimsrud@kreftregisteret.no
RI Friesen, Melissa/A-5362-2009;
OI Kjaerheim, Kristina/0000-0003-0691-3735
FU Research Council of Norway's PETROMAKS program; Department of Global
Public Health and Primary Care, University of Bergen, Norway; National
Cancer Institute, National Institutes of Health, Bethesda, Maryland
FX This study was funded by a grant to the Cancer Registry of Norway from
the Research Council of Norway's PETROMAKS program. MB is funded by the
Department of Global Public Health and Primary Care, University of
Bergen, Norway. MCF is funded by the intramural research program of the
National Cancer Institute, National Institutes of Health, Bethesda,
Maryland.
NR 15
TC 1
Z9 1
U1 0
U2 8
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1545-9624
EI 1545-9632
J9 J OCCUP ENVIRON HYG
JI J. Occup. Environ. Hyg.
PD JUL 3
PY 2015
VL 12
IS 7
BP 458
EP 468
DI 10.1080/15459624.2014.989358
PG 11
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health
GA CK6EX
UT WOS:000356322400001
PM 25671393
ER
PT J
AU Noh, KM
Wang, HB
Kim, HR
Wenderski, W
Fang, F
Li, CH
Dewell, S
Hughes, SH
Melnick, AM
Patel, DJ
Li, HT
Allis, CD
AF Noh, Kyung-Min
Wang, Haibo
Kim, Hyunjae R.
Wenderski, Wendy
Fang, Fang
Li, Charles H.
Dewell, Scott
Hughes, Stephen H.
Melnick, Ari M.
Patel, Dinshaw J.
Li, Haitao
Allis, C. David
TI Engineering of a Histone-Recognition Domain in Dnmt3a Alters the
Epigenetic Landscape and Phenotypic Features of Mouse ESCs
SO MOLECULAR CELL
LA English
DT Article
ID EMBRYONIC STEM-CELLS; DE-NOVO METHYLATION; METHYLTRANSFERASE GENE
DNMT3A; DNA METHYLATION; THR-3 PHOSPHORYLATION; MAMMALIAN DEVELOPMENT;
H3 METHYLTRANSFERASE; PHD FINGER; AURORA B; CHROMATIN
AB Histone modification and DNA methylation are associated with varying epigenetic "landscapes,''but detailed mechanistic and functional links between the two remain unclear. Using the ATRX-DNMT3-DNMT3L (ADD) domain of the DNA methyltransferase Dnmt3a as a paradigm, we apply protein engineering to dissect the molecular interactions underlying the recruitment of this enzyme to specific regions of chromatin in mouse embryonic stem cells (ESCs). By rendering the ADD domain insensitive to histone modification, specifically H3K4 methylation or H3T3 phosphorylation, we demonstrate the consequence of dysregulated Dnmt3a binding and activity. Targeting of a Dnmt3a mutant to H3K4me3 promoters decreases gene expression in a subset of developmental genes and alters ESC differentiation, whereas aberrant binding of another mutant to H3T3ph during mitosis promotes chromosome instability. Our studies support the general view that histone modification "reading'' and DNA methylation are closely coupled in mammalian cells, and suggest an avenue for the functional assessment of chromatin-associated proteins.
C1 [Noh, Kyung-Min; Wenderski, Wendy; Li, Charles H.; Allis, C. David] Rockefeller Univ, Lab Chromatin Biol & Epigenet, New York, NY 10065 USA.
[Noh, Kyung-Min] European Mol Biol Lab, Genome Biol Unit, D-69117 Heidelberg, Germany.
[Wang, Haibo; Li, Haitao] Tsinghua Univ, Sch Med, Dept Basic Med Sci, Beijing 100084, Peoples R China.
[Wang, Haibo; Li, Haitao] Tsinghua Univ, Sch Life Sci, Struct Biol Ctr, MOE Key Lab Prot Sci, Beijing 100084, Peoples R China.
[Kim, Hyunjae R.] Rockefeller Univ, Lab RNA Mol Biol, New York, NY 10065 USA.
[Fang, Fang; Melnick, Ari M.] Weill Cornell Med Coll, Dept Med Hematol Oncol, New York, NY 10021 USA.
[Dewell, Scott] Rockefeller Univ, Genom Resource Ctr, New York, NY 10065 USA.
[Hughes, Stephen H.] NCI, Drug Resistance Program 4, Ctr Canc Res, Frederick, MD 21702 USA.
[Patel, Dinshaw J.] Mem Sloan Kettering Canc Ctr, Struct Biol Program, New York, NY 10021 USA.
[Li, Haitao] Sichuan Univ, West China Hosp, Collaborat Innovat Ctr Biotherapy, Chengdu 610041, Peoples R China.
RP Li, HT (reprint author), Tsinghua Univ, Sch Med, Dept Basic Med Sci, Beijing 100084, Peoples R China.
EM lht@tsinghua.edu.cn; alliscd@rockefeller.edu
RI Li, Haitao/B-2668-2012;
OI Li, Haitao/0000-0001-6741-293X; Kim, Ryan/0000-0002-1869-0412
FU Women & Science Postdoctoral Fellowship; NIMH grant [PHS MH 094698];
Leukemia Lymphoma Society Program Project Award [NORTHWESTERN-LLS
7006-13]; STARR Foundation Awards [I5-A554, I5-A558]; National Natural
Science Foundation of China [31270763]; Major State Basic Research
Development Program in China [2011CB965300]; New Century Excellent
Talents in University; National Cancer Institute
FX We thank M. Okano for Dnmt TKO ESCs. We thank members of the Allis
laboratory for technical advice and discussion. We thank the staff at
beamlines BL17U of the Shanghai Synchrotron Radiation Facility and
24ID-E of the Advanced Photon Source at the Argonne National Laboratory
for their assistance in data collection. We also thank the staff at the
Epigenomics Core Facility of Weill Cornell Medical College, the
Rockefeller University Genomics Resource Center, the Bio-Imaging
Resource Center, the Flow Cytometry Resource Center, and at the
Molecular Cytogenetics, the Molecular Cytology, and the Center of
Comparative Medicine and Pathology of Memorial Sloan Kettering Cancer
Center. This work is supported by a Women & Science Postdoctoral
Fellowship (to K.-M.N.), a NIMH grant (PHS MH 094698, to C.D.A.), a
Leukemia Lymphoma Society Program Project Award (NORTHWESTERN-LLS
7006-13, to A.M.M., D.J.P., and C.D.A.), STARR Foundation Awards
(I5-A554 and I5-A558 to D.J.P.), program grants (The General Program of
National Natural Science Foundation of China, 31270763, The Major State
Basic Research Development Program in China, 2011CB965300 and Program
for New Century Excellent Talents in University, to H.L.), and funds
from the National Cancer Institute (to S.H.). The content of this
publication does not necessarily reflect the views or policies of the
Department of Health and Human Services, nor does the mention of trade
names, commercial products, or organizations imply endorsement by the
U.S. Government.
NR 51
TC 16
Z9 16
U1 1
U2 21
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 JUL 2
PY 2015
VL 59
IS 1
BP 89
EP 103
DI 10.1016/j.molcel.2015.05.017
PG 15
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CR0DB
UT WOS:000360987300009
PM 26073541
ER
PT J
AU Visweswaraiah, J
Pittman, Y
Dever, TE
Hinnebusch, AG
AF Visweswaraiah, Jyothsna
Pittman, Yvette
Dever, Thomas E.
Hinnebusch, Alan G.
TI The beta-hairpin of 40S exit channel protein Rps5/uS7 promotes efficient
and accurate translation initiation in vivo
SO ELIFE
LA English
DT Article
ID START CODON SELECTION; FACTOR 1 EIF1; PREINITIATION COMPLEX;
SACCHAROMYCES-CEREVISIAE; SCANNING MECHANISM; RIBOSOMAL-SUBUNIT;
MULTIPLE STEPS; GTP HYDROLYSIS; AUG SELECTION; E SITE
AB The eukaryotic 43S pre-initiation complex bearing tRNA(i)(Met) scans the mRNA leader for an AUG start codon in favorable context. Structural analyses revealed that the beta-hairpin of 40S protein Rps5/uS7 protrudes into the 40S mRNA exit-channel, contacting the eIF2.GTP.Met-tRNA(i) ternary complex (TC) and mRNA context nucleotides; but its importance in AUG selection was unknown. We identified substitutions in beta-strand-1 and C-terminal residues of yeast Rps5 that reduced bulk initiation, conferred 'leaky-scanning' of AUGs; and lowered initiation fidelity by exacerbating the effect of poor context of the eIF1 AUG codon to reduce eIF1 abundance. Consistently, the beta-strand-1 substitution greatly destabilized the 'P-IN' conformation of TC binding to reconstituted 43S.mRNA complexes in vitro. Other substitutions in beta-hairpin loop residues increased initiation fidelity and destabilized P-IN at UUG, but not AUG start codons. We conclude that the Rps5 beta-hairpin is as crucial as soluble initiation factors for efficient and accurate start codon recognition.
C1 [Visweswaraiah, Jyothsna; Pittman, Yvette; Dever, Thomas E.; Hinnebusch, Alan G.] NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA.
RP Dever, TE (reprint author), NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA.
EM Dever@nih.gov; ahinnebusch@nih.gov
OI Dever, Thomas/0000-0001-7120-9678
FU National Institutes of Health (NIH) Intramural Program
FX National Institutes of Health (NIH) Intramural Program Alan G Hinnebusch
NR 46
TC 5
Z9 5
U1 0
U2 4
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD JUL 2
PY 2015
VL 4
AR e07939
DI 10.7554/eLife.07939
PG 21
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA CO1OC
UT WOS:000358923800001
PM 26134896
ER
PT J
AU Botkin, JR
Belmont, JW
Berg, JS
Berkman, BE
Bombard, Y
Holm, IA
Levy, HP
Ormond, KE
Saal, HM
Spinner, NB
Wilfond, BS
McInerney, JD
AF Botkin, Jeffrey R.
Belmont, John W.
Berg, Jonathan S.
Berkman, Benjamin E.
Bombard, Yvonne
Holm, Ingrid A.
Levy, Howard P.
Ormond, Kelly E.
Saal, Howard M.
Spinner, Nancy B.
Wilfond, Benjamin S.
McInerney, Joseph D.
CA ASHG Workgrp Pediat Genetic Genomi
TI Points to Consider: Ethical, Legal, and Psychosocial Implications of
Genetic Testing in Children and Adolescents
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID TAY-SACHS-DISEASE; HEALTH-CARE PROVIDERS; INCIDENTAL FINDINGS;
REPRODUCTIVE BENEFIT; CARRIER STATUS; DEVELOPMENTAL-DISABILITIES;
MISATTRIBUTED PATERNITY; PRENATAL-DIAGNOSIS; SCREENING-PROGRAM; PARENTAL
CONSENT
AB In 1995, the American Society of Human Genetics (ASHG) and American College of Medical Genetics and Genomics (ACMG) jointly published a statement on genetic testing in children and adolescents. In the past 20 years, much has changed in the field of genetics, including the development of powerful new technologies, new data from genetic research on children and adolescents, and substantial clinical experience. This statement represents current opinion by the ASHG on the ethical, legal, and social issues concerning genetic testing in children. These recommendations are relevant to families, clinicians, and investigators. After a brief review of the 1995 statement and major changes in genetic technologies in recent years, this statement offers points to consider on a broad range of test technologies and their applications in clinical,medicine and research. Recommendations are also made for record and communication issues in this domain and for professional education.
C1 [Botkin, Jeffrey R.] Univ Utah, Salt Lake City, UT 84112 USA.
[Belmont, John W.] Baylor Coll Med, Houston, TX 77030 USA.
[Berg, Jonathan S.] Univ N Carolina, Chapel Hill, NC 27599 USA.
[Berkman, Benjamin E.] NHGRI, Bethesda, MD 20892 USA.
[Bombard, Yvonne] Univ Toronto, Toronto, ON M5B 1T8, Canada.
[Bombard, Yvonne] St Michaels Hosp, Li Ka Shing Knowledge Inst, Toronto, ON M5B 1W8, Canada.
[Holm, Ingrid A.] Boston Childrens Hosp, Boston, MA 02115 USA.
[Levy, Howard P.] Johns Hopkins Univ, Baltimore, MD 21205 USA.
[Ormond, Kelly E.] Stanford Univ, Stanford, CA 94305 USA.
[Saal, Howard M.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
[Spinner, Nancy B.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Wilfond, Benjamin S.] Seattle Childrens Hosp, Seattle, WA 98101 USA.
[McInerney, Joseph D.] Amer Soc Human Genet, Bethesda, MD 20814 USA.
RP Botkin, JR (reprint author), Univ Utah, Salt Lake City, UT 84112 USA.
EM jeffrey.botkin@hsc.utah.edu
OI Berg, Jonathan/0000-0003-2360-2664
FU NCATS NIH HHS [UL1 TR001067]
NR 109
TC 49
Z9 50
U1 10
U2 38
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
EI 1537-6605
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD JUL 2
PY 2015
VL 97
IS 1
BP 6
EP 21
DI 10.1016/j.ajhg.2015.05.022
PG 16
WC Genetics & Heredity
SC Genetics & Heredity
GA CN1OO
UT WOS:000358189500002
PM 26140447
ER
PT J
AU Darabi, H
Mccue, K
Beesley, J
Michailidou, K
Nord, S
Kar, S
Humphreys, K
Thompson, D
Ghoussaini, M
Bolla, MK
Dennis, J
Wang, Q
Canisius, S
Scott, CG
Apicella, C
Hopper, JL
Southey, MC
Stone, J
Broeks, A
Schmidt, MK
Scott, RJ
Lophatananon, A
Muir, K
Beckmann, MW
Ekici, AB
Fasching, PA
Heusinger, K
dos-Santos-Silva, I
Peto, J
Tomlinson, I
Sawyer, EJ
Burwinkel, B
Marme, F
Guenel, P
Truong, T
Bojesen, SE
Flyger, H
Benitez, J
Gonzalez-Neira, A
Anton-Culver, H
Neuhausen, SL
Arndt, V
Brenner, H
Engel, C
Meindl, A
Schmutzler, RK
Arnold, N
Brauch, H
Hamann, U
Chang-Claude, J
Khan, S
Nevanlinna, H
Ito, H
Matsuo, K
Bogdanova, NV
Dork, T
Lindblom, A
Margolin, S
Kosma, VM
Mannermaa, A
Tseng, CC
Wu, AH
Floris, G
Lambrechts, D
Rudolph, A
Peterlongo, P
Radice, P
Couch, FJ
Vachon, C
Giles, GG
McLean, C
Milne, RL
Dugue, PA
Haiman, CA
Maskarinec, G
Woolcott, C
Henderson, BE
Goldberg, MS
Simard, J
Teo, SH
Mariapun, S
Helland, A
Haakensen, V
Zheng, W
Beeghly-Fadiel, A
Tamimi, R
Jukkola-Vuorinen, A
Winqvist, R
Andrulis, IL
Knight, JA
Devilee, P
Tollenaar, RAEM
Figueroa, J
Garcia-Closas, M
Czene, K
Hooning, MJ
Tilanus-Linthorst, M
Li, JM
Gao, YT
Shu, XO
Cox, A
Cross, SS
Luben, R
Khaw, KT
Choi, JY
Kang, D
Hartman, M
Lim, WY
Kabisch, M
Torres, D
Jakubowska, A
Lubinski, J
McKay, J
Sangrajrang, S
Toland, AE
Yannoukakos, D
Shen, CY
Yu, JC
Ziogas, A
Schoemaker, MJ
Swerdlow, A
Borresen-Dale, AL
Kristensen, V
French, JD
Edwards, SL
Dunning, AM
Easton, DF
Hal, P
Chenevix-Trench, G
AF Darabi, Hatef
Mccue, Karen
Beesley, Jonathan
Michailidou, Kyriaki
Nord, Silje
Kar, Siddhartha
Humphreys, Keith
Thompson, Deborah
Ghoussaini, Maya
Bolla, Manjeet K.
Dennis, Joe
Wang, Qin
Canisius, Sander
Scott, Christopher G.
Apicella, Carmel
Hopper, John L.
Southey, Melissa C.
Stone, Jennifer
Broeks, Annegien
Schmidt, Marjanka K.
Scott, Rodney J.
Lophatananon, Artitaya
Muir, Kenneth
Beckmann, Matthias W.
Ekici, Arif B.
Fasching, Peter A.
Heusinger, Katharina
dos-Santos-Silva, Isabel
Peto, Julian
Tomlinson, Ian
Sawyer, Elinor J.
Burwinkel, Barbara
Marme, Frederik
Guenel, Pascal
Truong, Therese
Bojesen, Stig E.
Flyger, Henrik
Benitez, Javier
Gonzalez-Neira, Anna
Anton-Culver, Hoda
Neuhausen, Susan L.
Arndt, Volker
Brenner, Hermann
Engel, Christoph
Meindl, Alfons
Schmutzler, Rita K.
Arnold, Norbert
Brauch, Hiltrud
Hamann, Ute
Chang-Claude, Jenny
Khan, Sofia
Nevanlinna, Heli
Ito, Hidemi
Matsuo, Keitaro
Bogdanova, Natalia V.
Doerk, Thilo
Lindblom, Annika
Margolin, Sara
Kosma, Veli-Matti
Mannermaa, Arto
Tseng, Chiu-Chen
Wu, Anna H.
Floris, Giuseppe
Lambrechts, Diether
Rudolph, Anja
Peterlongo, Paolo
Radice, Paolo
Couch, Fergus J.
Vachon, Celine
Giles, Graham G.
McLean, Catriona
Milne, Roger L.
Dugue, Pierre-Antoine
Haiman, Christopher A.
Maskarinec, Gertraud
Woolcott, Christy
Henderson, Brian E.
Goldberg, Mark S.
Simard, Jacques
Teo, Soo H.
Mariapun, Shivaani
Helland, Aslaug
Haakensen, Vilde
Zheng, Wei
Beeghly-Fadiel, Alicia
Tamimi, Rulla
Jukkola-Vuorinen, Aria
Winqvist, Robert
Andrulis, Irene L.
Knight, Julia A.
Devilee, Peter
Tollenaar, Robert A. E. M.
Figueroa, Jonine
Garcia-Closas, Montserrat
Czene, Kamila
Hooning, Maartje J.
Tilanus-Linthorst, Madeleine
Li, Jingmei
Gao, Yu-Tang
Shu, Xiao-Ou
Cox, Angela
Cross, Simon S.
Luben, Robert
Khaw, Kay-Tee
Choi, Ji-Yeob
Kang, Daehee
Hartman, Mikael
Lim, Wei Yen
Kabisch, Maria
Torres, Diana
Jakubowska, Anna
Lubinski, Jan
McKay, James
Sangrajrang, Suleeporn
Toland, Amanda E.
Yannoukakos, Drakoulis
Shen, Chen-Yang
Yu, Jyh-Cherng
Ziogas, Argyrios
Schoemaker, Minouk J.
Swerdlow, Anthony
Borresen-Dale, Anne-Lise
Kristensen, Vessela
French, Juliet D.
Edwards, Stacey L.
Dunning, Alison M.
Easton, Douglas F.
Hal, Per
Chenevix-Trench, Georgia
CA German Consortium Hereditary Breas
kConFab-AOCS Investigators
TI Polymorphisms in a Putative Enhancer at the 10q21.2 Breast Cancer Risk
Locus Regulate NRBF2 Expression
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; BRCA2 MUTATION CARRIERS; MAMMOGRAPHIC DENSITY;
COMMON VARIANTS; GENOTYPE IMPUTATION; ZNF365; TUMORS; ARCHITECTURE;
STABILITY; AUTOPHAGY
AB Genome-wide association studies have identified SNPs near ZNF365 at 10q21.2 that are associated with both breast cancer risk and mammographic density. To identify the most likely causal SNPs, we fine mapped the association signal by genotyping 428 SNPs across the region in 89,050 European and 12,893 Asian case and control subjects from the Breast Cancer Association Consortium. We identified four independent sets of correlated, highly trait-associated variants (iCHAVs), three of which were located within ZNF365. The most strongly risk-associated SNP, rs10995201 in iCHAV1, showed clear evidence of association with both estrogen receptor (ER)-positive (OR = 0.85 10.82-0.881) and ER-negative (OR = 0.87 [0.82-0.911) disease, and was also the SNP most strongly associated with percent mammographic density. iCHAV2 (lead SNP, chr10: 64,258,684:0) and iCHAV3 (lead SNP, rs7922449) were also associated with ER-positive (OR = 0.93 10.91-0.951 and OR = 1.06 [1.03-1.091) and ER-negative (OR = 0.95 [0.91-0.98] and OR = 1.08 [1.04-1.131) disease. There was weaker evidence for iCHAV4, located 5' of ADO, associated only with ER-positive breast cancer (OR = 0.93 [0.90-0.961). We found 12, 17, 18, and 2 candidate causal SNPs for breast cancer in iCHAVs 1-4, respectively. Chromosome conformation capture analysis showed that iCHAV2 interacts with the ZNF365 and NRBF2 (more than 600 kb away) promoters in normal and cancerous breast epithelial cells. Luciferase assays did not identify SNPs that affect transactivation of ZNF365, but identified a protective haplotype in iCHAV2, associated with silencing of the NRBF2 promoter, implicating this gene in the etiology of breast cancer.
C1 [Darabi, Hatef; Humphreys, Keith; Czene, Kamila; Hal, Per] Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden.
[Mccue, Karen; Beesley, Jonathan; French, Juliet D.; Edwards, Stacey L.; Chenevix-Trench, Georgia] QIMR Berghofer Med Res Inst, Dept Genet, Brisbane, Qld 4006, Australia.
[Michailidou, Kyriaki; Thompson, Deborah; Bolla, Manjeet K.; Dennis, Joe; Wang, Qin; Easton, Douglas F.] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England.
[Nord, Silje; Borresen-Dale, Anne-Lise; Kristensen, Vessela] Radiumhosp, Oslo Univ Hosp, Inst Canc Res, Dept Genet, N-0310 Oslo, Norway.
[Nord, Silje] Univ Oslo, Fac Med, Inst Clin Med, KG Jebsen Ctr Breast Canc Res, N-0450 Oslo, Norway.
[Kar, Siddhartha; Ghoussaini, Maya; Dunning, Alison M.; Easton, Douglas F.] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England.
[Canisius, Sander; Broeks, Annegien; Schmidt, Marjanka K.] Anton van Leeuwenhoek Hosp, Netherlands Canc Inst, NL-1066 CX Amsterdam, Netherlands.
[Apicella, Carmel; Hopper, John L.; Giles, Graham G.; Milne, Roger L.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic 3010, Australia.
[Southey, Melissa C.] Univ Melbourne, Dept Pathol, Melbourne, Vic 3010, Australia.
[Stone, Jennifer] Univ Western Australia, Ctr Genet Origins Hlth & Dis, Crawley, WA 6009, Australia.
[Scott, Rodney J.] Univ Newcastle, Sch Biomed Sci & Pharm, Discipline Med Genet, Fac Hlth, Newcastle, NSW 2308, Australia.
[Scott, Rodney J.] John Hunter Hosp, Div Mol Med, Pathol North, Newcastle, NSW 2305, Australia.
[Scott, Rodney J.] Hunter Med Res Inst, Newcastle, NSW 2305, Australia.
[Lophatananon, Artitaya; Muir, Kenneth] Univ Warwick, Warwick Med Sch, Div Hlth Sci, Coventry CV4 7AL, W Midlands, England.
[Muir, Kenneth] Univ Manchester, Inst Populat Hlth, Manchester M13 9PL, Lancs, England.
[Beckmann, Matthias W.; Fasching, Peter A.; Heusinger, Katharina] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Gynecol & Obstet, Univ Breast Ctr Franconia,Ctr Erlangen EMN, D-91054 Erlangen, Germany.
[Ekici, Arif B.] Univ Erlangen Nurnberg, Inst Human Genet, Univ Hosp Erlangen, Comprehens Canc Ctr Erlangen EMN, D-91054 Erlangen, Germany.
[Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Div Hematol & Oncol, Dept Med, Los Angeles, CA 90095 USA.
[dos-Santos-Silva, Isabel; Peto, Julian] Univ London London Sch Hyg & Trop Med, Dept Noncommunicable Dis Epidemol, London WC1E 7HT, England.
[Tomlinson, Ian] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
[Tomlinson, Ian] Univ Oxford, Oxford Biomed Res Ctr, Oxford OX3 7BN, England.
[Sawyer, Elinor J.] Guys Hosp, Div Canc Studies, Kings Coll London, Res Oncol, London SE1 9RT, England.
[Burwinkel, Barbara; Marme, Frederik] Heidelberg Univ, Natl Ctr Tumor Dis, D-69120 Heidelberg, Germany.
[Burwinkel, Barbara] German Canc Res Ctr DZFK, Div Mol Gent Epidemiol, D-69047 Heidelberg, Germany.
[Marme, Frederik] Heidelberg Univ, Dept Obstet & Gynecol, D-69120 Heidelberg, Germany.
[Guenel, Pascal; Truong, Therese] Univ Paris Sud, UMRS 1018, F-94807 Villejuif, France.
[Guenel, Pascal; Truong, Therese] INSERM Natl Inst Hlth & Med Res, CESP Ctr Res Epidemiol & Populat Hlth, U1018, Environm Epidemiol Canc, F-94807 Villejuif, France.
[Bojesen, Stig E.] Copenhagen Univ Hosp, Herlev Hosp, Copenhagen Gen Populat Study, DK-2730 Herlev, Denmark.
[Bojesen, Stig E.] Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, DK-2730 Herlev, Denmark.
[Bojesen, Stig E.] Univ Copenhagen, Fac Hlth & Med Sci, DK-2200 Copenhagen, Denmark.
[Flyger, Henrik] Copenhagen Univ Hosp, Herlev Hosp, Dept Breast Surg, DK-2730 Herlev, Denmark.
[Benitez, Javier; Gonzalez-Neira, Anna] Spanish Natl Canc Res Ctr CNIO, Human Canc Genet Program, Human Gen CEGEN Unit, Madrid 28029, Spain.
[Benitez, Javier] Spanish Natl Canc Ctr CNIO, Human Genet Grp, Madrid 28029, Spain.
[Benitez, Javier] Biomed Network Rare Dis CIBERER, Madrid 28029, Spain.
[Anton-Culver, Hoda; Ziogas, Argyrios] Univ Calif Irvine, Dept Epidemiol, Irvine, CA 92697 USA.
[Neuhausen, Susan L.] City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA.
[Arndt, Volker; Brenner, Hermann] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, D-69120 Heidelberg, Germany.
[Brenner, Hermann] German Canc Res Ctr, Div Prevent Oncol, D-69120 Heidelberg, Germany.
[Brenner, Hermann; Brauch, Hiltrud] German Canc Res Ctr, German Canc Consortium DKTK, D-69120 Heidelberg, Germany.
[Engel, Christoph] Univ Leipzig, Inst Med Informat Stat & Epidemiol, D-04107 Leipzig, Germany.
[Meindl, Alfons] Tech Univ Munich, Div Gynaecol & Obstet, D-81675 Munich, Germany.
[Schmutzler, Rita K.] Univ Cologne, Ctr Mol Med Cologne CMMC, D-50932 Cologne, Germany.
[Schmutzler, Rita K.] Univ Hosp Cologne, Fac Med, Ctr Hereditary Breast & Ovarian Canc, D-50937 Cologne, Germany.
[Schmutzler, Rita K.] Univ Hosp Cologne, Fac Med, Ctr Integrated Oncol CIO, D-50937 Cologne, Germany.
[Arnold, Norbert] Univ Kiel, Dept Obstet & Gynaecol, Univ Hosp Schleswig Holstein, D-24105 Kiel, Germany.
[Brauch, Hiltrud] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-70376 Stuttgart, Germany.
[Brauch, Hiltrud] Univ Tubingen, D-72074 Tubingen, Germany.
[Hamann, Ute; Kabisch, Maria; Torres, Diana] German Canc Res Ctr, Mol Genet Breast Canc, D-69120 Heidelberg, Germany.
[Chang-Claude, Jenny; Rudolph, Anja] German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Germany.
[Khan, Sofia; Nevanlinna, Heli] Univ Helsinki, Dept Obstet & Gynecol, Helsinki 00029, HUS, Finland.
[Khan, Sofia; Nevanlinna, Heli] Helsinki Univ Hosp, Helsinki 00029, HUS, Finland.
[Ito, Hidemi] Aichi Canc Ctr, Res Inst, Div Epidemiol & Prevent, Nagoya, Aichi 4648681, Japan.
[Matsuo, Keitaro] Kyushu Univ, Fac Med Sci, Dept Prevent Med, Fukuoka 8128582, Japan.
[Bogdanova, Natalia V.] Hannover Med Sch, Dept Radiat Oncol, D-30625 Hannover, Germany.
[Doerk, Thilo] Hannover Med Sch, Gynaecol Res Unit, D-30625 Hannover, Germany.
[Lindblom, Annika] Karolinska Inst, Dept Mol Med & Surg, S-17177 Stockholm, Sweden.
[Margolin, Sara] Karolinska Inst, Dept Oncol Pathol, S-17177 Stockholm, Sweden.
[Kosma, Veli-Matti; Mannermaa, Arto] Univ Eastern Finland, Inst Clin Med Pathol & Forens Med, Sch Med, Kuopio 70211, Finland.
[Kosma, Veli-Matti; Mannermaa, Arto] Kuopio Univ Hosp, Dept Clin Pathol, Imaging Ctr, Kuopio 70211, Finland.
[Kosma, Veli-Matti; Mannermaa, Arto] Univ Eastern Finland, Canc Ctr Eastern Finland, Kuopio 70211, Finland.
[Tseng, Chiu-Chen; Wu, Anna H.; Haiman, Christopher A.; Henderson, Brian E.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Floris, Giuseppe] Univ Hosp Gashuisberg, B-3000 Leuven, Belgium.
[Lambrechts, Diether] VIB, Vesalius Res Ctr VRC, B-3000 Leuven, Belgium.
[Lambrechts, Diether] Univ Leuven, Dept Oncol, Lab Translat Genet, B-3000 Leuven, Belgium.
[Peterlongo, Paolo] IFOM, Inst Mol Oncol, I-20139 Milan, Italy.
[Radice, Paolo] INT, Unit Mol Bases Genet Risk & Genet Testing, Dept Prevent & Predict Med, Fdn IRCCS Ist Ricovero & Cura Carattere Sci, I-20133 Milan, Italy.
[Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA.
[Giles, Graham G.; Milne, Roger L.; Dugue, Pierre-Antoine] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic 3053, Australia.
[McLean, Catriona] Alfred Hosp, Anat Pathol, Melbourne, Vic 3004, Australia.
[Maskarinec, Gertraud] Univ Hawaii, Canc Epidemiol Program, Ctr Canc, Honolulu, HI 96813 USA.
[Woolcott, Christy] Dalhousie Univ, Dept Obstet & Gynaecol, Halifax, NS B3H 4R2, Canada.
[Woolcott, Christy] Dalhousie Univ, Dept Pediat, Halifax, NS B3H 4R2, Canada.
[Goldberg, Mark S.] McGill Univ, Dept Med, Montreal, PQ H3A 1W7, Canada.
[Simard, Jacques] McGill Univ, Royal Victoria Hosp, Div Clin Epidemiol, Ctr Hlth, Montreal, PQ H3H 2R9, Canada.
[Simard, Jacques] Ctr Hosp Univ Quebec, Res Ctr, Quebec City, PQ G1V 4G2, Canada.
[Simard, Jacques] Univ Laval, Quebec City, PQ G1V 4G2, Canada.
[Teo, Soo H.; Mariapun, Shivaani] Univ Malaya, Med Ctr UMMC, Breast Canc Res Unit, Canc Res Inst, Kuala Lumpur 50603, Malaysia.
[Teo, Soo H.; Mariapun, Shivaani] Canc Res Initiat Fdn, Sime Darby Med Ctr, Subang Jaya 47500, Malaysia.
[Helland, Aslaug] Radiumhosp, Oslo Univ Hosp, Dept Oncol, N-0310 Oslo, Norway.
[Haakensen, Vilde] Radiumhosp, Oslo Univ Hosp, Dept Genet, N-0310 Oslo, Norway.
[Zheng, Wei; Beeghly-Fadiel, Alicia; Shu, Xiao-Ou] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Div Epidemiol,Dept Med,Vanderbilt Epidemiol Ctr, Nashville, TN 37203 USA.
[Tamimi, Rulla] Brigham & Womens Hosp, Dept Med, Charming Div Network Med, Boston, MA 02115 USA.
[Tamimi, Rulla] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Tamimi, Rulla] Harvard Univ, Sch Med, Program Mol & Genet Epidemiol, Boston, MA 02115 USA.
[Tamimi, Rulla] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Jukkola-Vuorinen, Aria] Oulu Univ Hosp, Dept Oncol, Oulu 90014, Finland.
[Jukkola-Vuorinen, Aria] Univ Oulu, Oulu 90014, Finland.
[Winqvist, Robert] Univ Oulu, Lab Canc Genet & Tumor Biol, Dept Clin Chem, Oulu 90014, Finland.
[Winqvist, Robert] Univ Oulu, Bioctr Oulu, Oulu 90014, Finland.
[Winqvist, Robert] Northern Finland Lab Ctr NordLab, Lab Canc Genet & Tumor Biol, Oulu 90220, Finland.
[Andrulis, Irene L.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada.
[Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 3G3, Canada.
[Andrulis, Irene L.] Univ Toronto, Dept Lab Med, Toronto, ON M5S 3G3, Canada.
[Andrulis, Irene L.] Univ Toronto, Dept Pathobiol, Toronto, ON M5S 3G3, Canada.
[Knight, Julia A.] Mt Sinai Hosp, Prosserman Ctr Hlth Res, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada.
[Knight, Julia A.] Univ Toronto, Dalla Lana Sch Publ Hlth, Div Epidemiol, Toronto, ON M5S 3G3, Canada.
[Devilee, Peter] Leiden Univ, Med Ctr, Dept Human Genet, NL-2333 ZA Leiden, Netherlands.
[Devilee, Peter] Leiden Univ, Dept Pathol, Med Ctr, NL-2333 ZA Leiden, Netherlands.
[Tollenaar, Robert A. E. M.] Leiden Univ, Med Ctr, Dept Surg Oncol, NL-2333 ZC Leiden, Netherlands.
[Figueroa, Jonine] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20850 USA.
[Garcia-Closas, Montserrat; Schoemaker, Minouk J.; Swerdlow, Anthony] Inst Canc Res, Div Genet & Epidemiol, Sutton SM2 5NG, Surrey, England.
[Garcia-Closas, Montserrat] Breakthrough Breast Canc Res Ctr, Div Canc Studies, London SW3 6JB, England.
[Hooning, Maartje J.] Erasmus MC Canc Inst, Dept Med Oncol, NL-3008 AE Rotterdam, Netherlands.
[Tilanus-Linthorst, Madeleine] Erasmus Univ, Med Ctr, Dept Surg Oncol, NL-3075 EA Rotterdam, Netherlands.
[Li, Jingmei] Genome Inst Singapore, Div Human Genet, Singapore 138672, Singapore.
[Gao, Yu-Tang] Shanghai Canc Inst, Dept Epidemiol, Shanghai 200031, Peoples R China.
[Cox, Angela] Univ Sheffield, Dept Oncol, Canc Res Ctr, Sheffield S10 2RX, S Yorkshire, England.
[Cross, Simon S.] Univ Sheffield, Dept Neurosci, Acad Unit Pathol, Sheffield S10 2HQ, S Yorkshire, England.
[Luben, Robert] Univ Cambridge, Dept Publ Hlth & Primary Care, Clin Gerontol, Cambridge CB1 8RN, England.
[Khaw, Kay-Tee] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge CB2 1TN, England.
[Choi, Ji-Yeob; Kang, Daehee] Seoul Natl Univ, Dept Biomed Sci, Coll Med, Seoul 110799, South Korea.
[Choi, Ji-Yeob; Kang, Daehee] Seoul Natl Univ, Coll Med, Dept Surg, Seoul 110799, South Korea.
[Kang, Daehee] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul 110799, South Korea.
[Hartman, Mikael; Lim, Wei Yen] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117597, Singapore.
[Hartman, Mikael; Lim, Wei Yen] Natl Univ Singapore, Dept Surg, Singapore 117597, Singapore.
[Lim, Wei Yen] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Surg, Singapore 119228, Singapore.
[Lim, Wei Yen] Natl Univ Hlth Syst, Singapore 119228, Singapore.
[Torres, Diana] Pontificia Univ Javeriana, Inst Human Genet, Bogota 12362, Colombia.
[Jakubowska, Anna; Lubinski, Jan] Pomeranian Med Univ, Dept Genet & Pathol, PL-70115 Szczecin, Poland.
[McKay, James] Int Agcy Res Canc, F-69372 Lyon 08, France.
[Sangrajrang, Suleeporn] Natl Canc Inst, Bangkok 10400, Thailand.
[Toland, Amanda E.] Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Ctr Comprehens Canc, Columbus, OH 43210 USA.
[Yannoukakos, Drakoulis] Aghia Paraskevi Attikis, Natl Ctr Sci Res Demokritos, Mol Diagnost Lab, IRRP, Athens 15310, Greece.
[Shen, Chen-Yang] Acad Sinica, Inst Biomed Sci, Taiwan Biobank, Taipei 115, Taiwan.
[Shen, Chen-Yang] China Med Univ, Sch Publ Hlth, Taichung 40402, Taiwan.
[Yu, Jyh-Cherng] Triserv Gen Hosp, Dept Surg, Taipei 114, Taiwan.
[Swerdlow, Anthony] Inst Canc Res, Div Breast Canc Res, Sutton SM2 5NG, Surrey, England.
[Borresen-Dale, Anne-Lise; Kristensen, Vessela] Univ Oslo UiO, Inst Clin Med, N-0316 Oslo, Norway.
[Kristensen, Vessela] Univ Oslo UiO, Dept Clin Mol Biol EpiGen, N-0316 Oslo, Norway.
RP Chenevix-Trench, G (reprint author), QIMR Berghofer Med Res Inst, Dept Genet, Brisbane, Qld 4006, Australia.
EM georgia.trench@qimr.edu.au
RI Teo, Soo-hwang/H-2353-2014; Helland, Aslaug/H-3910-2015; Andrulis,
Irene/E-7267-2013; Edwards, Stacey/A-4980-2011; Nord, Silje/R-5212-2016;
Brenner, Hermann/B-4627-2017; Li, Jingmei/I-2904-2012; Hartman,
Mikael/B-4324-2011; Knight, Julia/A-6843-2012; Dork, Thilo/J-8620-2012;
Arnold, Norbert/E-3012-2010; U-ID, Kyushu/C-5291-2016
OI benitez, javier/0000-0002-0923-7202; Cross, Simon/0000-0003-2044-1754;
Luben, Robert/0000-0002-5088-6343; Dunning, Alison
Margaret/0000-0001-6651-7166; Khan, Sofia/0000-0003-4185-8882; dos
Santos Silva, Isabel/0000-0002-6596-8798; Cox,
Angela/0000-0002-5138-1099; Yannoukakos, Drakoulis/0000-0001-7509-3510;
Giles, Graham/0000-0003-4946-9099; Arndt, Volker/0000-0001-9320-8684;
Helland, Aslaug/0000-0002-5520-0275; Nord, Silje/0000-0002-3271-5356;
Brenner, Hermann/0000-0002-6129-1572; Schoemaker,
Minouk/0000-0001-8403-2234; Li, Jingmei/0000-0001-8587-7511; Arnold,
Norbert/0000-0003-4523-8808;
FU Cancer Research UK [14136]; Medical Research Council [G0401527,
G1000143]; NCI NIH HHS [R01 CA176785, P01 CA082267, P50 CA116201, R01
CA128978, U01 CA116167]
NR 38
TC 7
Z9 9
U1 2
U2 17
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
EI 1537-6605
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD JUL 2
PY 2015
VL 97
IS 1
BP 22
EP 34
DI 10.1016/j.ajhg.2015.05.002
PG 13
WC Genetics & Heredity
SC Genetics & Heredity
GA CN1OO
UT WOS:000358189500003
PM 26073781
ER
PT J
AU Shah, S
Bonder, MJ
Marioni, RE
Zhu, ZH
McRae, AF
Zhernakova, A
Harris, SE
Liewald, D
Henders, AK
Mendelson, MM
Liu, CY
Joehanes, R
Liang, LM
Levy, D
Martin, NG
Starr, JM
Wijmenga, C
Wray, NR
Yang, J
Montgomery, GW
Franke, L
Deary, IJ
Visscher, PM
AF Shah, Sonia
Bonder, Marc J.
Marioni, Riccardo E.
Zhu, Zhihong
McRae, Allan F.
Zhernakova, Alexandra
Harris, Sarah E.
Liewald, Dave
Henders, Anjali K.
Mendelson, Michael M.
Liu, Chunyu
Joehanes, Roby
Liang, Liming
Levy, Daniel
Martin, Nicholas G.
Starr, John M.
Wijmenga, Cisca
Wray, Naomi R.
Yang, Jian
Montgomery, Grant W.
Franke, Lude
Deary, Ian J.
Visscher, Peter M.
CA BIOS Consortium
TI Improving Phenotypic Prediction by Combining Genetic and Epigenetic
Associations
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID BODY-MASS INDEX; DNA METHYLATION; WEIGHT-LOSS; CARDIOVASCULAR-DISEASE;
GENOTYPE IMPUTATION; WIDE ASSOCIATION; GENOME; OBESITY; HEIGHT;
POPULATION
AB We tested whether DNA-methylation profiles account for inter-individual variation in body mass index (BMI) and height and whether they predict these phenotypes over and above genetic factors. Genetic predictors were derived from published summary results from the largest genome-wide association studies on BMI (n similar to 350,000) and height (n similar to 250,000) to date. We derived methylation predictors by estimating probe-trait effects in discovery samples and tested them in external samples. Methylation profiles associated with BMI in older individuals from the Lothian Birth Cohorts (LBCs, n = 1,366) explained 4.9% of the variation in BMI in Dutch adults from the Life Lines DEEP study (n = 750) but did not account for any BMI variation in adolescents from the Brisbane Systems Genetic Study (BSGS, n = 403). Methylation profiles based on the Dutch sample explained 4.9% and 3.6% of the variation in BMI in the LBCs and BSGS, respectively. Methylation profiles predicted BMI independently of genetic profiles in an additive manner: 7%, 8%, and 140/0 of variance of BMI in the LBCs were explained by the methylation predictor, the genetic predictor, and a model containing both, respectively. The corresponding percentages for Life Lines DEEP were 5%, 9%, and 13%, respectively, suggesting that the methylation profiles represent environmental effects. The differential effects of the BM! methylation profiles by age support previous observations of age modulation of genetic contributions. In contrast, methylation profiles accounted for almost no variation in height, consistent with a mainly genetic contribution to inter-individual variation. The BMI results suggest that combining genetic and epigenetic information might have greater utility for complex-trait prediction.
C1 [Shah, Sonia; Marioni, Riccardo E.; Zhu, Zhihong; McRae, Allan F.; Wray, Naomi R.; Yang, Jian; Visscher, Peter M.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia.
[Shah, Sonia; McRae, Allan F.; Visscher, Peter M.] Univ Queensland, Translat Res Inst, Diamantina Inst, Brisbane, Qld 4072, Australia.
[Bonder, Marc J.; Zhernakova, Alexandra; Wijmenga, Cisca; Franke, Lude] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9713 AV Groningen, Netherlands.
[Marioni, Riccardo E.; Harris, Sarah E.; Liewald, Dave; Starr, John M.; Deary, Ian J.; Visscher, Peter M.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.
[Marioni, Riccardo E.; Harris, Sarah E.] Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Med Genet Sect, Edinburgh EH4 2XU, Midlothian, Scotland.
[Henders, Anjali K.; Martin, Nicholas G.; Montgomery, Grant W.] Berghofer Med Res Inst, Queensland Inst Med Res, Brisbane, Qld 4029, Australia.
[Mendelson, Michael M.] Framingham Heart Dis Epidemiol Study, Boston, MA 01702 USA.
[Mendelson, Michael M.] Boston Univ, Sch Med, Boston, MA 01702 USA.
[Mendelson, Michael M.] Boston Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA.
[Mendelson, Michael M.; Levy, Daniel] NHLBI, Populat Studies Branch, NIH, Bethesda, MD 20892 USA.
[Liu, Chunyu] Boston Univ, Dept Biostat, Boston, MA 02118 USA.
[Joehanes, Roby] Harvard Univ, Sch Med, Hebrew Senior Life, Boston, MA 02131 USA.
[Liang, Liming] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Liang, Liming] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Starr, John M.; Deary, Ian J.] Univ Edinburgh, Dept Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland.
RP Visscher, PM (reprint author), Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia.
EM peter.visscher@uq.edu.au
RI Montgomery, Grant/B-7148-2008; Shah, Sonia/N-7547-2013; Suchiman, H. Eka
D./F-5024-2017; Mendelson, Michael/I-2874-2014; Yang, Jian/A-5852-2010;
McRae, Allan/J-2644-2014; Pool, Rene/B-3652-2009; Franke,
Lude/P-7036-2016; Slagboom, P. Eline/R-4790-2016;
OI Montgomery, Grant/0000-0002-4140-8139; Shah, Sonia/0000-0001-5860-4526;
Suchiman, H. Eka D./0000-0002-7168-5516; Mendelson,
Michael/0000-0001-7590-3958; Yang, Jian/0000-0003-2001-2474; McRae,
Allan/0000-0001-5286-5485; Pool, Rene/0000-0001-5579-0933; Franke,
Lude/0000-0002-5159-8802; Slagboom, P. Eline/0000-0002-2875-4723;
Zhernakova, Alexandra/0000-0002-4574-0841; Visscher,
Peter/0000-0002-2143-8760; Bonder, Marc Jan/0000-0002-8431-3180
FU Biotechnology and Biological Sciences Research Council [BB/F019394/1];
Medical Research Council [MR/K026992/1]
NR 43
TC 12
Z9 12
U1 3
U2 18
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
EI 1537-6605
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD JUL 2
PY 2015
VL 97
IS 1
BP 75
EP 85
DI 10.1016/j.ajhg.2015.05.014
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA CN1OO
UT WOS:000358189500007
PM 26119815
ER
PT J
AU Marchegiani, S
Davis, T
Tessadori, F
van Haaften, G
Brancati, F
Hoischen, A
Huang, HG
Valkanas, E
Pusey, B
Schanze, D
Venselaar, H
Vulto-van Silfhout, AT
Wolfe, LA
Tifft, CJ
Zerfas, PM
Zambruno, G
Kariminejad, A
Sabbagh-Kermani, F
Lee, J
Tsokos, MG
Lee, CCR
Ferraz, V
da Silva, EM
Stevens, CA
Roche, N
Bartsch, O
Farndon, P
Bermejo-Sanchez, E
Brooks, BP
Maduro, V
Dallapiccola, B
Ramos, FJ
Chung, HYB
Le Caignec, C
Martins, F
Jacyk, WK
Mazzanti, L
Brunner, HG
Bakkers, J
Lin, S
Malicdan, MCV
Boerkoel, CF
Gahl, WA
de Vries, BBA
van Haelst, MM
Zenker, M
Markello, TC
AF Marchegiani, Shannon
Davis, Taylor
Tessadori, Federico
van Haaften, Gijs
Brancati, Francesco
Hoischen, Alexander
Huang, Haigen
Valkanas, Elise
Pusey, Barbara
Schanze, Denny
Venselaar, Hanka
Vulto-van Silfhout, Anneke T.
Wolfe, Lynne A.
Tifft, Cynthia J.
Zerfas, Patricia M.
Zambruno, Giovanna
Kariminejad, Ariana
Sabbagh-Kermani, Farahnaz
Lee, Janice
Tsokos, Maria G.
Lee, Chyi-Chia R.
Ferraz, Victor
da Silva, Eduarda Morgana
Stevens, Cathy A.
Roche, Nathalie
Bartsch, Oliver
Farndon, Peter
Bermejo-Sanchez, Eva
Brooks, Brian P.
Maduro, Valerie
Dallapiccola, Bruno
Ramos, Feliciano J.
Chung, Hon-Yin Brian
Le Caignec, Cedric
Martins, Fabiana
Jacyk, Witold K.
Mazzanti, Laura
Brunner, Han G.
Bakkers, Jeroen
Lin, Shuo
Malicdan, May Christine V.
Boerkoel, Cornelius F.
Gahl, William A.
de Vries, Bert B. A.
van Haelst, Mieke M.
Zenker, Martin
Markello, Thomas C.
TI Recurrent Mutations in the Basic Domain of TWIST2 Cause Ablepharon
Macrostomia and Barber-Say Syndromes
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID MORPHOLOGY STANDARD TERMINOLOGY; EPITHELIAL-MESENCHYMAL TRANSITION;
AUTOSOMAL-DOMINANT INHERITANCE; SAETHRE-CHOTZEN SYNDROME; SETLEIS
SYNDROME; ATROPHIC SKIN; UNDIAGNOSED DISEASES; TRANSCRIPTION FACTOR;
FRAMESHIFT MUTATION; FAMILIAL OCCURRENCE
AB Ablepharon macrostomia syndrome (AMS) and Barber-Say syndrome (BSS) are rare congenital ectodermal dysplasias characterized by similar clinical features. To establish the genetic basis of AMS and BSS, we performed extensive clinical phenotyping, whole exome and candidate gene sequencing, and functional validations. We identified a recurrent de novo mutation in TWIST2 in seven independent AMS-affected families, as well as another recurrent de novo mutation affecting the same amino acid in ten independent BSS-affected families. Moreover, a genotype-phenotype correlation was observed, because the two syndromes differed based solely upon the nature of the substituting amino acid: a lysine at TWIST2 residue 75 resulted in AMS, whereas a glutamine or alanine yielded BSS. TW1ST2 encodes a basic helix-loop-helix transcription factor that regulates the development of mesenchymal tissues. All identified mutations fell in the basic domain of TWIST2 and altered the DNA-binding pattern of Flag-1'WIST2 in HeLa cells. Comparison of wild-type and mutant TW1ST2 expressed in zebrafish identified abnormal developmental phenotypes and widespread transcriptome changes. Our results suggest that autosomal-dominant TW1ST2 mutations cause AMS or BSS by inducing protean effects on the transcription factor's DNA binding.
C1 [Marchegiani, Shannon; Davis, Taylor; Valkanas, Elise; Pusey, Barbara; Wolfe, Lynne A.; Tifft, Cynthia J.; Maduro, Valerie; Malicdan, May Christine V.; Boerkoel, Cornelius F.; Gahl, William A.; Markello, Thomas C.] NIH, Undiagnosed Dis Program, Common Fund, Off Director, Bethesda, MD 20892 USA.
[Marchegiani, Shannon; Davis, Taylor; Valkanas, Elise; Pusey, Barbara; Wolfe, Lynne A.; Tifft, Cynthia J.; Maduro, Valerie; Malicdan, May Christine V.; Boerkoel, Cornelius F.; Gahl, William A.; Markello, Thomas C.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Marchegiani, Shannon] Walter Reed Natl Mil Med Ctr, Dept Pediat, Bethesda, MD 20892 USA.
[Tessadori, Federico; Bakkers, Jeroen] Hubrecht Inst KNAW, NL-3584 CT Utrecht, Netherlands.
[Tessadori, Federico; Bakkers, Jeroen] Univ Med Ctr Utrecht, NL-3584 CT Utrecht, Netherlands.
[van Haaften, Gijs; van Haelst, Mieke M.] Univ Med Ctr Utrecht, Dept Med Genet, NL-3508 AB Utrecht, Netherlands.
[Brancati, Francesco] Univ G dAnnunzio Chieti & Pescara, Dept Med Oral & Biotechnol Sci, I-66100 Chieti, Italy.
[Hoischen, Alexander; Venselaar, Hanka; Vulto-van Silfhout, Anneke T.; Brunner, Han G.; de Vries, Bert B. A.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 GA Nijmegen, Netherlands.
[Huang, Haigen; Lin, Shuo] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA.
[Schanze, Denny; Zenker, Martin] Fak Med, D-39120 Magdeburg, Germany.
[Schanze, Denny; Zenker, Martin] Univ Klinikum Magdeburg, Inst Human Genet, D-39120 Magdeburg, Germany.
[Wolfe, Lynne A.; Tifft, Cynthia J.; Malicdan, May Christine V.; Gahl, William A.] NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA.
[Zerfas, Patricia M.] NIH, Off Res Serv, Div Vet Resources, Bethesda, MD 20892 USA.
[Zambruno, Giovanna] Ist Dermopat Immacolata IDI IRCCS, Lab Mol & Cell Biol, I-00167 Rome, Italy.
[Kariminejad, Ariana] Kariminejad Najmabadi Pathol & Genet Ctr, Tehran 14667, Iran.
[Sabbagh-Kermani, Farahnaz] Kerman Univ Med Sci, Kerman 76175, Iran.
[Lee, Janice] NIDCR, NIH, Bethesda, MD 20892 USA.
[Tsokos, Maria G.; Lee, Chyi-Chia R.] NCI, Lab Pathol, NIH, Bethesda, MD 20892 USA.
[Ferraz, Victor; da Silva, Eduarda Morgana] Univ Sao Paulo, Dept Genet, Fac Med Ribeirao Preto, BR-14049 Sao Paulo, Brazil.
[Stevens, Cathy A.] TC Thompson Childrens Hosp, Dept Med Genet, Chattanooga, TN 37403 USA.
[Roche, Nathalie] Univ Hosp Ghent, Dept Plast & Reconstruct Surg, B-9000 Ghent, Belgium.
[Bartsch, Oliver] Johannes Gutenberg Univ Mainz, Inst Human Genet, D-55131 Mainz, Germany.
[Farndon, Peter] Birmingham Womens Healthcare Trust, Clin Genet Unit, Birmingham B15 2TG, W Midlands, England.
[Bermejo-Sanchez, Eva] Inst Salud Carlos III, ECEMC Spanish Collaborat Study Congenital Malform, CIAC, IIER, Madrid 28029, Spain.
[Bermejo-Sanchez, Eva] CIBER Enfermedades Raras CIBERER U724, Madrid 28029, Spain.
[Brooks, Brian P.] NEI, Unit Pediat Dev & Genet Eye Dis, NIH, Bethesda, MD 20892 USA.
[Dallapiccola, Bruno] Bambino Gesu Pediat Hosp, Dept Med Genet, IRCCS, I-00165 Rome, Italy.
[Ramos, Feliciano J.] Univ Zaragoza, GCV CIBERER Hosp Clin Univ Lozano Blesa, Serv Pediat, Unidad Genet Med,Fac Med, E-50009 Zaragoza, Spain.
[Chung, Hon-Yin Brian] Univ Hong Kong, LKS Fac Med, Ctr Genom Sci, Dept Paediat & Adolescent Med, Hong Kong, Hong Kong, Peoples R China.
[Le Caignec, Cedric] CHU Nantes, Serv Genet Med, F-44093 Nantes, France.
[Le Caignec, Cedric] INSERM, Fac Med, UMR957, F-44093 Nantes, France.
[Martins, Fabiana] Univ Sao Paulo, Sch Dent, Dept Stomatol, Special Care Dent Ctr, BR-05508070 Sao Paulo, Brazil.
[Jacyk, Witold K.] Univ Pretoria, Dept Dermatol, ZA-0028 Pretoria, South Africa.
[Mazzanti, Laura] Univ Bologna, S Orsola Malpighi Hosp, Dept Pediat, I-40138 Bologna, Italy.
[Brunner, Han G.] Maastricht Univ, Med Ctr, Dept Clin Genet, NL-6202 AZ Maastricht, Netherlands.
RP Malicdan, MCV (reprint author), NIH, Undiagnosed Dis Program, Common Fund, Off Director, Bethesda, MD 20892 USA.
EM malicdanm@mail.nih.gov; gahlw@helix.nih.gov
RI van Haaften, Gijs/G-7832-2012; Le Caignec, Cedric/K-8467-2015; Brunner,
Han/C-9928-2013; Hoischen, Alexander/D-1282-2013; Ferraz,
Victor/A-8774-2013; Vulto-van Silfhout, Anneke/H-4199-2015; Venselaar,
Hanka/D-2009-2016; BERMEJO-SANCHEZ, EVA/E-8703-2012; Dallapiccola,
Bruno/K-8692-2016
OI van Haaften, Gijs/0000-0003-3033-0329; Le Caignec,
Cedric/0000-0002-0598-653X; Hoischen, Alexander/0000-0002-8072-4476;
BERMEJO-SANCHEZ, EVA/0000-0001-7282-2714; Bakkers,
Jeroen/0000-0002-9418-0422; Dallapiccola, Bruno/0000-0002-5031-1013
FU Intramural Research Program of the NHGRI; Netherlands Organization for
Health Research and Development [319 912-12-109]; Wilhelmina Children's
Hospital fund; Netherlands Organization for Health Research and
Development veni grant [916-12-095]
FX We thank the patients, their families, and the treating physicians for
their cooperation, encouragement, and interest. This work was supported
by the Intramural Research Program of the NHGRI, Netherlands
Organization for Health Research and Development grant 319 912-12-109
(B.B.A.d.V.), Wilhelmina Children's Hospital fund (G.v.H.), and
Netherlands Organization for Health Research and Development veni grant
916-12-095 (A.H.). One AMS fibroblast cell line was from NICHD Brain and
Tissue Bank for Developmental Disorders (N01-HD-4-3368/N01-HD-4-3383).
We are grateful to the following: Dr. Michael Wright (Northern Genetics
Service, Newcastle upon Tyne Hospitals, UK), Dr. Salmo Raskin
(Laboratorio Genetika, Alameda Augusto Stellfeld, Curitiba Parana,
Brazil), Dr. Donna M. McDonald-McGinn (Clinical Genetics Center,
Children's Hospital of Philadelphia), Dr. Edward Cowan (NCI/NIH,
Bethesda, MD), Dr. Maria Luisa Martinez-Frias (University Complutense
and CIAC/ISCIII, Madrid, Spain), Dr. Elena Campione (Dermatology Unit of
Tor Vergata University, Rome, Italy), Dr. Frederic Perez-Alvarez
(Hospital Universitari de Girona Dr. Josep Trueta, Spain), Dra. Beatriz
Lopez-Garcia (Hospital Quiron-La Floresta, Zaragoza, Spain), Dr. Anthony
Liu and Dr. K.Y. Wong (QMH, Hong Kong), Dr. T.Y. Tan (Royal Children's
Hospital, Melbourne, Australia), Prof. Marina Gallottini (Department of
Stomatology, Dental School of USP, Brazil), Prof. Raoul C.M. Hennekam
(Academic Medical Center, University of Amsterdam, the Netherlands),
Prof. Wilson Araujo Silva, Jr. (Department of Genetics and Center of
Genomic Medicine, Riberao Preto University/Clinical Hospital, Brazil),
and Dr. Luis Rohena (San Antonio Military Medical Center, TX). The views
expressed in this article are those of the authors and do not reflect
the official policy of the Department of Army/Navy/Air Force, Department
of Defense, or U.S. Government.
NR 67
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PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
EI 1537-6605
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD JUL 2
PY 2015
VL 97
IS 1
BP 99
EP 110
DI 10.1016/j.ajhg.2015.05.017
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA CN1OO
UT WOS:000358189500009
PM 26119818
ER
PT J
AU Groza, T
Kohler, S
Moldenhauer, D
Vasilevsky, N
Baynam, G
Zemojtel, T
Schriml, LM
Kibbe, WA
Schofield, PN
Beck, T
Vasant, D
Brookes, AJ
Zankl, A
Washington, NL
Mungall, CJ
Lewis, SE
Haendel, MA
Parkinson, H
Robinson, PN
AF Groza, Tudor
Koehler, Sebastian
Moldenhauer, Dawid
Vasilevsky, Nicole
Baynam, Gareth
Zemojtel, Tomasz
Schriml, Lynn Marie
Kibbe, Warren Alden
Schofield, Paul N.
Beck, Tim
Vasant, Drashtti
Brookes, Anthony J.
Zankl, Andreas
Washington, Nicole L.
Mungall, Christopher J.
Lewis, Suzanna E.
Haendel, Melissa A.
Parkinson, Helen
Robinson, Peter N.
TI The Human Phenotype Ontology: Semantic Unification of Common and Rare
Disease
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; RISK LOCI; GENETIC-VARIANTS; IDENTIFICATION;
DISORDERS; DATABASE; SUSCEPTIBILITY; MUTATIONS; MEDICINE; RESOURCE
AB The Human Phenotype Ontology (HPO) is widely used in the rare disease community for differential diagnostics, phenotype-driven analysis of next-generation sequence-variation data, and translational research, but a comparable resource has not been available for common disease. Here, we have developed a concept-recognition procedure that analyzes the frequencies of HPO disease annotations as identified in over five million Pub Med abstracts by employing an iterative procedure to optimize precision and recall of the identified terms. We derived disease models for 3,145 common human diseases comprising a total of 132,006 HPO annotations. The HPO now comprises over 250,000 phenotypic annotations for over 10,000 rare and common diseases and can be used for examining the phenotypic overlap among common diseases that share risk alleles, as well as between Mendelian diseases and common diseases linked by genomic location. The annotations, as well as the HPO itself, are freely available.
C1 [Groza, Tudor] Univ Queensland, Sch Informat Technol & Elect Engn, St Lucia, Qld 4072, Australia.
[Groza, Tudor; Zankl, Andreas] Garvan Inst Med Res, Sydney, NSW 2010, Australia.
[Koehler, Sebastian; Moldenhauer, Dawid; Zemojtel, Tomasz; Robinson, Peter N.] Charite, Inst Med & Human Genet, D-13353 Berlin, Germany.
[Moldenhauer, Dawid] Univ Appl Sci, D-35390 Giessen, Germany.
[Vasilevsky, Nicole] Oregon Hlth & Sci Univ, Lib, Portland, OR 97239 USA.
[Baynam, Gareth] Univ Western Australia, Sch Paediat & Child Hlth, Perth, WA 6840, Australia.
[Baynam, Gareth] Murdoch Univ, Inst Immunol & Infect Dis, Perth, WA 6150, Australia.
[Baynam, Gareth] Off Populat Hlth Genom, Publ Hlth & Clin Serv Div, Dept Hlth, Perth, WA 6004, Australia.
[Baynam, Gareth] King Edward Mem Hosp, Genet Serv Western Australia, Perth, WA 6008, Australia.
[Baynam, Gareth] Telethon Kids Inst, Perth, WA 6008, Australia.
[Zemojtel, Tomasz] Polish Acad Sci, Inst Bioorgan Chem, PL-61704 Poznan, Poland.
[Schriml, Lynn Marie] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Schriml, Lynn Marie] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA.
[Kibbe, Warren Alden] NCI, Ctr Biomed Informat & Informat Technol, Rockville, MD 20850 USA.
[Schofield, Paul N.] Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge CB2 3EG, England.
[Schofield, Paul N.] Jackson Lab, Bar Harbor, ME 04609 USA.
[Beck, Tim; Brookes, Anthony J.] Univ Leicester, Dept Genet, Leicester LE1 7RH, Leics, England.
[Vasant, Drashtti; Parkinson, Helen] European Bioinformat Inst, European Mol Biol Lab, Cambridge CB10 1SD, England.
[Zankl, Andreas] Childrens Hosp Westmead, Acad Dept Med Genet, Sydney, NSW 2145, Australia.
[Zankl, Andreas] Univ Sydney, Discipline Genet Med, Sydney Med Sch, Sydney, NSW 2145, Australia.
[Washington, Nicole L.; Mungall, Christopher J.; Lewis, Suzanna E.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Genom Div, Berkeley, CA 94720 USA.
[Robinson, Peter N.] Max Planck Inst Mol Genet, D-14195 Berlin, Germany.
[Robinson, Peter N.] Charite, Berlin Brandenburg Ctr Regenerat Therapies, D-13353 Berlin, Germany.
[Robinson, Peter N.] Free Univ Berlin, Dept Math & Comp Sci, Inst Bioinformat, D-14195 Berlin, Germany.
RP Robinson, PN (reprint author), Charite, Inst Med & Human Genet, Augustenburger Pl 1, D-13353 Berlin, Germany.
EM peter.robinson@charite.de
OI Parkinson, Helen/0000-0003-3035-4195; Kohler,
Sebastian/0000-0002-5316-1399; Lewis, Suzanna/0000-0002-8343-612X;
Schriml, Lynn/0000-0001-8910-9851; Vasilevsky,
Nicole/0000-0001-5208-3432
FU Bundesministerium fur Bildung und Forschung [0313911]; European
Commission [602300]; Raine Clinician Research Fellowship [20140101];
National Health and Medical Research Council of Australia [APP1055319,
305444]; NIH Office of the Director [1R24OD011883-01]; Australian
Research Council Discovery Early Career Researcher Award [DE120100508];
BioMedBridges project - Research Infrastructures of the FP7 [284209];
European Molecular Biology Laboratory Core Funds; Basic Energy Sciences,
Office of Science, US Department of Energy [DE-AC02-05CH11231]; NIH
[1R24OD011883-01]; US Government
FX This work was supported by the Bundesministerium fur Bildung und
Forschung (project 0313911), the European Commission Seventh Framework
Programme (FP7; grant 602300; SYBIL project), the Raine Clinician
Research Fellowship (20140101), and the National Health and Medical
Research Council of Australia (grant APP1055319, which is partnered with
FP7 grant 305444). Oregon Health and Science University acknowledges the
support of grant 1R24OD011883-01 from the NIH Office of the Director.
T.G. was supported by an Australian Research Council Discovery Early
Career Researcher Award (DE120100508). D.V. was supported in part by the
BioMedBridges project funded by Research Infrastructures of the FP7
(grant 284209). H.P. was supported by European Molecular Biology
Laboratory Core Funds. This work was supported by the director, Basic
Energy Sciences, Office of Science, US Department of Energy under
contract DE-AC02-05CH11231 and NIH contract 1R24OD011883-01. This
document was prepared as an account of work sponsored by the US
Government. While this document is believed to contain correct
information, neither the US Government nor any agency thereof, nor the
Regents of the University of California, nor any of their employees
makes any warranty, express or implied, or assumes any legal
responsibility for the accuracy, completeness, or usefulness of any
information, apparatus, product, or process disclosed or represents that
its use would not infringe privately owned rights. The views and
opinions of authors expressed herein do not necessarily state or reflect
those of the US Government or any agency thereof or the Regents of the
University of California.
NR 85
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PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
EI 1537-6605
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD JUL 2
PY 2015
VL 97
IS 1
BP 111
EP 124
DI 10.1016/j.ajhg.2015.05.020
PG 14
WC Genetics & Heredity
SC Genetics & Heredity
GA CN1OO
UT WOS:000358189500010
PM 26119816
ER
PT J
AU Eggers, SDZ
Horn, AKE
Roeber, S
Hartig, W
Nair, G
Reich, DS
Leigh, RJ
AF Eggers, Scott D. Z.
Horn, Anja K. E.
Roeber, Sigrun
Haertig, Wolfgang
Nair, Govind
Reich, Daniel S.
Leigh, R. John
TI Saccadic Palsy following Cardiac Surgery: Possible Role of Perineuronal
Nets
SO PLOS ONE
LA English
DT Article
ID ASCENDING AORTA DISSECTION; SYNDROME RESEMBLING PSP; OCULAR MOTOR
APRAXIA; EYE-MOVEMENTS; EXTRACELLULAR-MATRIX; OMNIPAUSE NEURONS; BURST
NEURONS; VERTICAL SACCADES; PREMOTOR NEURONS; FEEDBACK-CONTROL
AB Objective
Perineuronal nets (PN) form a specialized extracellular matrix around certain highly active neurons within the central nervous system and may help to stabilize synaptic contacts, promote local ion homeostasis, or play a protective role. Within the ocular motor system, excitatory burst neurons and omnipause neurons are highly active cells that generate rapid eye movements - saccades; both groups of neurons contain the calcium-binding protein parvalbumin and are ensheathed by PN. Experimental lesions of excitatory burst neurons and omnipause neurons cause slowing or complete loss of saccades. Selective palsy of saccades in humans is reported following cardiac surgery, but such cases have shown normal brainstem neuroimaging, with only one clinicopathological study that demonstrated paramedian pontine infarction. Our objective was to test the hypothesis that lesions of PN surrounding these brainstem saccade-related neurons may cause saccadic palsy.
Methods
Together with four controls we studied the brain of a patient who had developed a permanent selective saccadic palsy following cardiac surgery and died several years later. Sections of formalin-fixed paraffin-embedded brainstem blocks were applied to double-immunoperoxidase staining of parvalbumin and three different components of PN. Triple immunofluorescence labeling for all PN components served as internal controls. Combined immunostaining of parvalbumin and synaptophysin revealed the presence of synapses.
Results
Excitatory burst neurons and omnipause neurons were preserved and still received synaptic input, but their surrounding PN showed severe loss or fragmentation.
Interpretation
Our findings support current models and experimental studies of the brainstem saccade-generating neurons and indicate that damage to PN may permanently impair the function of these neurons that the PN ensheathe. How a postulated hypoxic mechanism could selectively damage the PN remains unclear. We propose that the well-studied saccadic eye movement system provides an accessible model to evaluate the role of PN in health and disease.
C1 [Eggers, Scott D. Z.] Mayo Clin, Dept Neurol, Minneapolis, MN 55455 USA.
[Horn, Anja K. E.] Univ Munich, Inst Anat & Cell Biol 1, Munich, Germany.
[Horn, Anja K. E.; Roeber, Sigrun] Univ Munich, German Ctr Vertigo & Balance Disorders, Munich, Germany.
[Roeber, Sigrun] Univ Munich, Inst Neuropathol & Pr Res, Munich, Germany.
[Haertig, Wolfgang] Univ Leipzig, Paul Flechsig Inst Brain Res, D-04109 Leipzig, Germany.
[Nair, Govind; Reich, Daniel S.] NINDS, NIH, Bethesda, MD 20892 USA.
[Leigh, R. John] Case Western Reserve Univ, Dept Neurol, Cleveland, OH 44106 USA.
RP Eggers, SDZ (reprint author), Mayo Clin, Dept Neurol, Minneapolis, MN 55455 USA.
EM eggers.scott@mayo.edu
RI Reich, Daniel/E-5701-2010
OI Reich, Daniel/0000-0002-2628-4334
FU Mayo Foundation for Medical Education and Research; Intramural Research
Program of the National Institute of Neurological Disorders and Stroke
[1 ZIA NS003119 05]; BMBF [IFBLMU 01EO0901, Brain-Net-01GI0505]
FX This work was supported by Mayo Foundation for Medical Education and
Research, Intramural Research Program of the National Institute of
Neurological Disorders and Stroke (1 ZIA NS003119 05), and BMBF (IFBLMU
01EO0901, Brain-Net-01GI0505).
NR 64
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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 JUL 2
PY 2015
VL 10
IS 7
AR e0132075
DI 10.1371/journal.pone.0132075
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN1CS
UT WOS:000358154400099
PM 26135580
ER
PT J
AU Skinner, PJ
Kim, HO
Bryant, D
Kinzel, NJ
Reilly, C
Priola, SA
Ward, AE
Goodman, PA
Olson, K
Seelig, DM
AF Skinner, Pamela J.
Kim, Hyeon O.
Bryant, Damani
Kinzel, Nikilyn J.
Reilly, Cavan
Priola, Suzette A.
Ward, Anne E.
Goodman, Patricia A.
Olson, Katherine
Seelig, Davis M.
TI Treatment of Prion Disease with Heterologous Prion Proteins
SO PLOS ONE
LA English
DT Article
ID TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES; CREUTZFELDT-JAKOB-DISEASE;
SPECIES BARRIERS; PRP ISOFORMS; CELLULAR PRP; IN-VITRO; SCRAPIE;
CONVERSION; RESISTANT; MICE
AB Prion diseases such as Creutzfeldt-Jakob disease in humans, bovine spongiform encephalopathy in cattle, and scrapie in sheep are fatal neurodegenerative diseases for which there is no effective treatment. The pathology of these diseases involves the conversion of a protease sensitive form of the cellular prion protein (PrPC) into a protease resistant infectious form (PrPsc or PrPres). Both in vitro (cell culture and cell free conversion assays) and in vivo (animal) studies have demonstrated the strong dependence of this conversion process on protein sequence homology between the initial prion inoculum and the host's own cellular prion protein. The presence of non-homologous (heterologous) proteins is often inhibitory to this conversion process. We hypothesize that the presence of heterologous prion proteins from one species might therefore constitute an effective treatment for prion disease in another species. To test this hypothesis, we infected mice intracerebrally with murine adapted RML-Chandler scrapie and treated them with heterologous prion protein (purified bacterially expressed recombinant hamster prion protein) or vehicle alone. Treated animals demonstrated reduced disease associated pathology, decreased accumulation of protease-resistant disease-associated prion protein, with delayed onset of clinical symptoms and motor deficits. This was concomitant with significantly increased survival times relative to mock-treated animals. These results provide proof of principle that recombinant hamster prion proteins can effectively and safely inhibit prion disease in mice, and suggest that hamster or other non-human prion proteins may be a viable treatment for prion diseases in humans.
C1 [Skinner, Pamela J.; Kim, Hyeon O.; Kinzel, Nikilyn J.; Goodman, Patricia A.; Olson, Katherine] Univ Minnesota, Vet & Biomed Sci Dept, St Paul, MN 55108 USA.
[Bryant, Damani; Seelig, Davis M.] Univ Minnesota, Dept Vet Clin Sci, St Paul, MN 55108 USA.
[Reilly, Cavan] Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA.
[Priola, Suzette A.; Ward, Anne E.] NIAID, Rocky Mt Lab, Persistent Viral Dis Lab, Hamilton, MT 59840 USA.
RP Skinner, PJ (reprint author), Univ Minnesota, Vet & Biomed Sci Dept, St Paul, MN 55108 USA.
EM skinn002@umn.edu
OI Skinner, Pamela/0000-0003-3388-1687
FU University of Minnesota Academic Health Center; Intramural Research
Program of the National Institute of Allergy & Infectious Disease,
National Institutes of Health
FX This work was supported by a seed grant from the University of Minnesota
Academic Health Center, PJS, and by the Intramural Research Program of
the National Institute of Allergy & Infectious Disease, National
Institutes of Health, SAP. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 50
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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 JUL 2
PY 2015
VL 10
IS 7
AR e0131993
DI 10.1371/journal.pone.0131993
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN1CS
UT WOS:000358154400091
PM 26134409
ER
PT J
AU Kaptchuk, TJ
Miller, FG
AF Kaptchuk, Ted J.
Miller, Franklin G.
TI Placebo Effects in Medicine
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
C1 [Kaptchuk, Ted J.] Beth Israel Deaconess Med Ctr, Program Placebo Studies, Boston, MA 02215 USA.
[Kaptchuk, Ted J.] Harvard Univ, Sch Med, Boston, MA USA.
[Miller, Franklin G.] NIH, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA.
RP Kaptchuk, TJ (reprint author), Beth Israel Deaconess Med Ctr, Program Placebo Studies, Boston, MA 02215 USA.
NR 5
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U1 4
U2 15
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUL 2
PY 2015
VL 373
IS 1
BP 8
EP 9
DI 10.1056/NEJMp1504023
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA CL8IS
UT WOS:000357218700003
PM 26132938
ER
PT J
AU Yoshizato, T
Dumitriu, B
Hosokawa, K
Makishima, H
Yoshida, K
Townsley, D
Sato-Otsubo, A
Sato, Y
Liu, D
Suzuki, H
Wu, CO
Shiraishi, Y
Clemente, MJ
Kataoka, K
Shiozawa, Y
Okuno, Y
Chiba, K
Tanaka, H
Nagata, Y
Katagiri, T
Kon, A
Sanada, M
Scheinberg, P
Miyano, S
Maciejewski, JP
Nakao, S
Young, NS
Ogawa, S
AF Yoshizato, T.
Dumitriu, B.
Hosokawa, K.
Makishima, H.
Yoshida, K.
Townsley, D.
Sato-Otsubo, A.
Sato, Y.
Liu, D.
Suzuki, H.
Wu, C. O.
Shiraishi, Y.
Clemente, M. J.
Kataoka, K.
Shiozawa, Y.
Okuno, Y.
Chiba, K.
Tanaka, H.
Nagata, Y.
Katagiri, T.
Kon, A.
Sanada, M.
Scheinberg, P.
Miyano, S.
Maciejewski, J. P.
Nakao, S.
Young, N. S.
Ogawa, S.
TI Somatic Mutations and Clonal Hematopoiesis in Aplastic Anemia
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; ACUTE MYELOID-LEUKEMIA; PIG-A GENE;
MYELODYSPLASTIC SYNDROMES; DNMT3A MUTATIONS; CELLS; CANCER; SURVIVAL;
AGE; MOSAICISM
AB BACKGROUND
In patients with acquired aplastic anemia, destruction of hematopoietic cells by the immune system leads to pancytopenia. Patients have a response to immunosuppressive therapy, but myelodysplastic syndromes and acute myeloid leukemia develop in about 15% of the patients, usually many months to years after the diagnosis of aplastic anemia.
METHODS
We performed next-generation sequencing and array-based karyotyping using 668 blood samples obtained from 439 patients with aplastic anemia. We analyzed serial samples obtained from 82 patients.
RESULTS
Somatic mutations in myeloid cancer candidate genes were present in one third of the patients, in a limited number of genes and at low initial variant allele frequency. Clonal hematopoiesis was detected in 47% of the patients, most frequently as acquired mutations. The prevalence of the mutations increased with age, and mutations had an age-related signature. DNMT3A-mutated and ASXL1-mutated clones tended to increase in size over time; the size of BCOR- and BCORL1-mutated and PIGA-mutated clones decreased or remained stable. Mutations in PIGA and BCOR and BCORL1 correlated with a better response to immunosuppressive therapy and longer and a higher rate of overall and progression-free survival; mutations in a subgroup of genes that included DNMT3A and ASXL1 were associated with worse outcomes. However, clonal dynamics were highly variable and might not necessarily have predicted the response to therapy and long-term survival among individual patients.
CONCLUSIONS
Clonal hematopoiesis was prevalent in aplastic anemia. Some mutations were related to clinical outcomes. A highly biased set of mutations is evidence of Darwinian selection in the failed bone marrow environment. The pattern of somatic clones in individual patients over time was variable and frequently unpredictable. (Funded by Grant-in-Aid for Scientific Research and others.)
C1 [Yoshizato, T.; Yoshida, K.; Sato-Otsubo, A.; Sato, Y.; Suzuki, H.; Kataoka, K.; Shiozawa, Y.; Nagata, Y.; Kon, A.; Sanada, M.; Ogawa, S.] Kyoto Univ, Grad Sch Med, Dept Pathol & Tumor Biol, Kyoto 6068501, Japan.
[Hosokawa, K.; Katagiri, T.; Nakao, S.] Kanazawa Univ, Grad Sch Med Sci, Dept Cellular Transplantat Biol, Div Canc Med, Kanazawa, Ishikawa, Japan.
[Shiraishi, Y.; Chiba, K.; Tanaka, H.; Miyano, S.] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Lab DNA Informat Anal, Tokyo, Japan.
[Okuno, Y.] Nagoya Univ, Grad Sch Med, Dept Pediat, Nagoya, Aichi 4648601, Japan.
[Dumitriu, B.; Hosokawa, K.; Townsley, D.; Liu, D.; Scheinberg, P.; Young, N. S.] NHLBI, Hematol Branch, Bethesda, MD 20892 USA.
[Wu, C. O.] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA.
[Makishima, H.; Clemente, M. J.; Maciejewski, J. P.] Cleveland Clin, Taussig Canc Inst, Dept Translat Hematol & Oncol Res, Cleveland, OH USA.
RP Ogawa, S (reprint author), Kyoto Univ, Grad Sch Med, Dept Pathol & Tumor Biol, Sakyo Ku, Yoshida Konoe Cho, Kyoto 6068501, Japan.
EM youngns@mail.nih.gov; sogawa-tky@umin.ac.jp
RI Okuno, Yusuke/C-9082-2009
OI Okuno, Yusuke/0000-0003-3139-9272
FU KAKENHI from Ministry of Health, Labor, and Welfare of Japan [22134006,
23249052, 26253060, 26221308]; Japan Society for the Promotion of
Science through Funding Program for World-Leading Innovative Research
and Development on Science and Technology; Intramural Research Program
of the National Heart, Lung, and Blood Institute; Aplastic Anemia and
MDS International Foundation; Scott Hamilton Cancer Alliance for
Research Education and Survivorship Foundation
FX Supported by Grant-in-Aid for Scientific Research (KAKENHI 22134006,
23249052, 26253060, and 26221308) from the Ministry of Health, Labor,
and Welfare of Japan and the Japan Society for the Promotion of Science
through the Funding Program for World-Leading Innovative Research and
Development on Science and Technology, the Intramural Research Program
of the National Heart, Lung, and Blood Institute, a grant from the
Aplastic Anemia and MDS International Foundation, and a research grant
from the Scott Hamilton Cancer Alliance for Research Education and
Survivorship Foundation.
NR 41
TC 51
Z9 60
U1 2
U2 18
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUL 2
PY 2015
VL 373
IS 1
BP 35
EP 47
DI 10.1056/NEJMoa1414799
PG 13
WC Medicine, General & Internal
SC General & Internal Medicine
GA CL8IS
UT WOS:000357218700006
PM 26132940
ER
PT J
AU Marongiu, M
Marcia, L
Pelosi, E
Lovicu, M
Deiana, M
Zhang, YQ
Puddu, A
Loi, A
Uda, M
Forabosco, A
Schlessinger, D
Crisponi, L
AF Marongiu, Mara
Marcia, Loredana
Pelosi, Emanuele
Lovicu, Mario
Deiana, Manila
Zhang, Yonqing
Puddu, Alessandro
Loi, Angela
Uda, Manuela
Forabosco, Antonino
Schlessinger, David
Crisponi, Laura
TI FOXL2 modulates cartilage, skeletal development and IGF1-dependent
growth in mice
SO BMC DEVELOPMENTAL BIOLOGY
LA English
DT Article
ID FOLLICLE-STIMULATING-HORMONE; EPICANTHUS INVERSUS SYNDROME;
TRANSCRIPTION FACTOR FOXL2; CRANIAL NEURAL CREST; OSTEOBLAST
DIFFERENTIATION; CAMPOMELIC DYSPLASIA; SIGNALING PATHWAY; BPES SYNDROME;
SEX REVERSAL; GENE SOX9
AB Background: Haploinsufficiency of the FOXL2 transcription factor in humans causes Blepharophimosis/Ptosis/ Epicanthus Inversus syndrome (BPES), characterized by eyelid anomalies and premature ovarian failure. Mice lacking Foxl2 recapitulate human eyelid/forehead defects and undergo female gonadal dysgenesis. We report here that mice lacking Foxl2 also show defects in postnatal growth and embryonic bone and cartilage formation.
Methods: Foxl2(-/-) male mice at different stages of development have been characterized and compared to wild type. Body length and weight were measured and growth curves were created. Skeletons were stained with alcian blue and/or alizarin red. Bone and cartilage formation was analyzed by Von Kossa staining and immunofluorescence using anti-FOXL2 and anti-SOX9 antibodies followed by confocal microscopy. Genes differentially expressed in skull vaults were evaluated by microarray analysis. Analysis of the GH/IGF1 pathway was done evaluating the expression of several hypothalamic-pituitary-bone axis markers by RT-qPCR.
Results: Compared to wild-type, Foxl2 null mice are smaller and show skeletal abnormalities and defects in cartilage and bone mineralization, with down-regulation of the GH/IGF1 axis. Consistent with these effects, we find FOXL2 expressed in embryos at 9.5 dpc in neural tube epithelium, in head mesenchyme near the neural tube, and within the first branchial arch; then, starting at 12.5 dpc, expressed in cartilaginous tissue; and at PO and P7, in hypothalamus.
Conclusions: Our results support FOXL2 as a master transcription factor in a spectrum of developmental processes, including growth, cartilage and bone formation. Its action overlaps that of SOX9, though they are antagonistic in female vs male gonadal sex determination but conjoint in cartilage and skeletal development.
C1 [Marongiu, Mara; Marcia, Loredana; Lovicu, Mario; Deiana, Manila; Puddu, Alessandro; Loi, Angela; Uda, Manuela; Crisponi, Laura] Cittadella Univ Monserrato, CNR, Ist Ric Genet & Biomed, I-09042 Monserrato, Italy.
[Marcia, Loredana] Univ Sassari, I-07100 Sassari, Italy.
[Pelosi, Emanuele; Zhang, Yonqing; Schlessinger, David] NIA IRP, Genet Lab, NIH, Baltimore, MD USA.
[Puddu, Alessandro] Univ Cagliari, Cagliari, Italy.
[Forabosco, Antonino] Cante Montevecchio Assoc, Genom Res Ctr, Fano, Italy.
RP Marongiu, M (reprint author), Cittadella Univ Monserrato, CNR, Ist Ric Genet & Biomed, SS 554 Km 4500, I-09042 Monserrato, Italy.
EM mara.marongiu@irgb.cnr.it
OI MARONGIU, MARA/0000-0002-7321-2384; Pelosi, Emanuele/0000-0003-1890-9821
FU Comitato Telethon Fondazione Onlus; Telethon grant [GP0049Y01]; Ricerca
Spontanea a Tema Libero CNR [DG.RSTL.060.001]; National Institute on
Aging, NIH
FX We thank Dr. Roberta Piras and Emilio Melis for their help with mouse
care and management, Dr. Luca Orru for supplying mice radiographies, Dr.
Walter Seu for helping us with microscope assisted pictures of P0 mice.
We thank Prof. Francesco Cucca, director of Institute of Genetic and
Biomedical Research. This work has been supported by Comitato Telethon
Fondazione Onlus, with Telethon grant to LC no GP0049Y01, Ricerca
Spontanea a Tema Libero CNR (DG.RSTL.060.001) to MU and in part by the
Intramural program of the National Institute on Aging, NIH. This paper
is dedicated to Prof. Giuseppe Pilia, whose role as a great source of
inspiration for the authors continues after his untimely death.
NR 49
TC 4
Z9 4
U1 3
U2 8
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 JUL 2
PY 2015
VL 15
AR 27
DI 10.1186/s12861-015-0072-y
PG 14
WC Developmental Biology
SC Developmental Biology
GA CL7LM
UT WOS:000357153600001
PM 26134413
ER
PT J
AU Sobral-Leite, M
Wesseling, J
Smit, VTHBM
Nevanlinna, H
van Miltenburg, MH
Sanders, J
Hofland, I
Blows, FM
Coulson, P
Patrycja, G
Schellens, JHM
Fagerholm, R
Heikkila, P
Aittomaki, K
Blomqvist, C
Provenzano, E
Ali, HR
Figueroa, J
Sherman, M
Lissowska, J
Mannermaa, A
Kataja, V
Kosma, VM
Hartikainen, JM
Phillips, KA
Couch, FJ
Olson, JE
Vachon, C
Visscher, D
Brenner, H
Butterbach, K
Arndt, V
Holleczek, B
Hooning, MJ
Hollestelle, A
Martens, JWM
van Deurzen, CHM
van de Water, B
Broeks, A
Chang-Claude, J
Chenevix-Trench, G
Easton, DF
Pharoah, PDP
Garcia-Closas, M
de Graauw, M
Schmidt, MK
AF Sobral-Leite, Marcelo
Wesseling, Jelle
Smit, Vincent T. H. B. M.
Nevanlinna, Heli
van Miltenburg, Martine H.
Sanders, Joyce
Hofland, Ingrid
Blows, Fiona M.
Coulson, Penny
Patrycja, Gazinska
Schellens, Jan H. M.
Fagerholm, Rainer
Heikkila, Paivi
Aittomaki, Kristiina
Blomqvist, Carl
Provenzano, Elena
Ali, Hamid Raza
Figueroa, Jonine
Sherman, Mark
Lissowska, Jolanta
Mannermaa, Arto
Kataja, Vesa
Kosma, Veli-Matti
Hartikainen, Jaana M.
Phillips, Kelly-Anne
Couch, Fergus J.
Olson, Janet E.
Vachon, Celine
Visscher, Daniel
Brenner, Hermann
Butterbach, Katja
Arndt, Volker
Holleczek, Bernd
Hooning, Maartje J.
Hollestelle, Antoinette
Martens, John W. M.
van Deurzen, Carolien H. M.
van de Water, Bob
Broeks, Annegien
Chang-Claude, Jenny
Chenevix-Trench, Georgia
Easton, Douglas F.
Pharoah, Paul D. P.
Garcia-Closas, Montserrat
de Graauw, Marjo
Schmidt, Marjanka K.
CA kConFab AOCS Investigators
TI Annexin A1 expression in a pooled breast cancer series: association with
tumor subtypes and prognosis
SO BMC MEDICINE
LA English
DT Article
DE Breast cancer; Annexin A1; BRCA1 and BRCA2 mutations
ID GROWTH-FACTOR; PROTEIN-KINASE; CELLS; PHOSPHORYLATION; CHEMOTHERAPY;
METASTASIS; SURVIVAL; COMPLEX; DIFFERENTIATION; ADENOCARCINOMA
AB Background: Annexin A1 (ANXA1) is a protein related with the carcinogenesis process and metastasis formation in many tumors. However, little is known about the prognostic value of ANXA1 in breast cancer. The purpose of this study is to evaluate the association between ANXA1 expression, BRCA1/2 germline carriership, specific tumor subtypes and survival in breast cancer patients.
Methods: Clinical-pathological information and follow-up data were collected from nine breast cancer studies from the Breast Cancer Association Consortium (BCAC) (n = 5,752) and from one study of familial breast cancer patients with BRCA1/2 mutations (n = 107). ANXA1 expression was scored based on the percentage of immunohistochemical staining in tumor cells. Survival analyses were performed using a multivariable Cox model.
Results: The frequency of ANXA1 positive tumors was higher in familial breast cancer patients with BRCA1/2 mutations than in BCAC patients, with 48.6 % versus 12.4 %, respectively; P < 0.0001. ANXA1 was also highly expressed in BCAC tumors that were poorly differentiated, triple negative, EGFR-CK5/6 positive or had developed in patients at a young age. In the first 5 years of follow-up, patients with ANXA1 positive tumors had a worse breast cancer-specific survival (BCSS) than ANXA1 negative (HRadj = 1.35; 95 % CI = 1.05-1.73), but the association weakened after 10 years (HRadj = 1.13; 95 % CI = 0.91-1.40). ANXA1 was a significant independent predictor of survival in HER2+ patients (10-years BCSS: HRadj = 1.70; 95 % CI = 1.17-2.45).
Conclusions: ANXA1 is overexpressed in familial breast cancer patients with BRCA1/2 mutations and correlated with poor prognosis features: triple negative and poorly differentiated tumors. ANXA1 might be a biomarker candidate for breast cancer survival prediction in high risk groups such as HER2+ cases.
C1 [Sobral-Leite, Marcelo; Wesseling, Jelle; van Miltenburg, Martine H.; Sanders, Joyce; Schellens, Jan H. M.; Schmidt, Marjanka K.] Netherlands Canc Inst, Div Mol Pathol, Amsterdam, Netherlands.
[Sobral-Leite, Marcelo] Inst Nacl Canc INCA, Programa Farmacol, Rio De Janeiro, RJ, Brazil.
[Wesseling, Jelle] Netherlands Canc Inst, Div Diagnost Oncol, Amsterdam, Netherlands.
[Smit, Vincent T. H. B. M.] Leiden Univ, Med Ctr, Dept Pathol, Leiden, Netherlands.
[Nevanlinna, Heli; Fagerholm, Rainer; Heikkila, Paivi; Blomqvist, Carl] Univ Helsinki, Helsinki, Finland.
[Nevanlinna, Heli; Fagerholm, Rainer] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, Helsinki, Finland.
[Hofland, Ingrid; Broeks, Annegien] Netherlands Canc Inst, Div Mol Pathol, Core Facil Mol Pathol & Biobanking, Amsterdam, Netherlands.
[Blows, Fiona M.; Easton, Douglas F.; Pharoah, Paul D. P.] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England.
[Coulson, Penny; Garcia-Closas, Montserrat] Inst Canc Res, Div Genet & Epidemiol, London SW3 6JB, England.
[Patrycja, Gazinska; Garcia-Closas, Montserrat] Breakthrough Breast Canc Ctr, London, England.
[Schellens, Jan H. M.] Utrecht Inst Pharmaceut Sci, Dept Pharmacoepidemiol & Clin Pharmacol, Utrecht, Netherlands.
[Heikkila, Paivi] Univ Helsinki, Cent Hosp, Dept Pathol, Helsinki, Finland.
[Aittomaki, Kristiina] Univ Helsinki, Cent Hosp, Dept Clin Genet, Helsinki, Finland.
[Blomqvist, Carl] Univ Helsinki, Cent Hosp, Dept Oncol, Helsinki, Finland.
[Provenzano, Elena; Ali, Hamid Raza] Univ Cambridge, Canc Res UK Cambridge Inst Oncol, Cambridge, MA USA.
[Provenzano, Elena] Cambridge Univ Hosp NHS Fdn Trust, Addenbrookes Hosp, Dept Histopathol, Cambridge, England.
[Ali, Hamid Raza] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England.
[Figueroa, Jonine; Sherman, Mark] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Sherman, Mark] NCI, Canc Prevent Div, Rockville, MD USA.
[Lissowska, Jolanta] Maria Sklodowska Curie Mem Canc Ctr & Inst Oncol, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
[Mannermaa, Arto; Kosma, Veli-Matti; Hartikainen, Jaana M.] Univ Eastern Finland, Sch Med, Inst Clin Med Pathol & Forens Med, Kuopio, Finland.
[Mannermaa, Arto; Kosma, Veli-Matti; Hartikainen, Jaana M.] Univ Eastern Finland, Canc Ctr Eastern Finland, Kuopio, Finland.
[Mannermaa, Arto; Kosma, Veli-Matti; Hartikainen, Jaana M.] Kuopio Univ Hosp, Dept Clin Pathol, Imaging Ctr, SF-70210 Kuopio, Finland.
[Kataja, Vesa] Kuopio Univ Hosp, Ctr Canc, SF-70210 Kuopio, Finland.
[Kataja, Vesa] Jyvaskyla Cent Hosp, Jyvaskyla, Finland.
[Phillips, Kelly-Anne] Peter MacCallum Canc Ctr, Div Canc Med, Melbourne, Vic, Australia.
[Phillips, Kelly-Anne] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia.
[Phillips, Kelly-Anne] Univ Melbourne, Sch Populat Hlth, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia.
[Phillips, Kelly-Anne] Univ Melbourne, St Vincents Hosp, Dept Med, Melbourne, Vic, Australia.
[Couch, Fergus J.; Visscher, Daniel] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
[Olson, Janet E.; Vachon, Celine] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
[Brenner, Hermann; Butterbach, Katja; Arndt, Volker] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
[Brenner, Hermann] German Canc Res Ctr, German Canc Consortium DKTK, Heidelberg, Germany.
[Brenner, Hermann] German Canc Res Ctr, Div Prevent Oncol, Heidelberg, Germany.
[Holleczek, Bernd] Saarland Canc Registry, Saarbrucken, Germany.
[Hooning, Maartje J.; Hollestelle, Antoinette; Martens, John W. M.] Erasmus MC Canc Inst, Dept Med Oncol, Rotterdam, Netherlands.
[van Deurzen, Carolien H. M.] Erasmus MC Canc Inst, Dept Pathol, Rotterdam, Netherlands.
[van de Water, Bob; de Graauw, Marjo] Leiden Univ, Leiden Acad Ctr Drug Res, Div Toxicol, Leiden, Netherlands.
[Chang-Claude, Jenny] German Canc Res Ctr, Unit Genet Epidemiol, Div Canc Epidemiol, Heidelberg, Germany.
[Chenevix-Trench, Georgia] QIMR Berghofer Med Res Inst, Dept Genet, Brisbane, Qld, Australia.
[Schmidt, Marjanka K.] Netherlands Canc Inst, Div Psychosocial Res & Epidemiol, NL-1066 CX Amsterdam, Netherlands.
RP Schmidt, MK (reprint author), Netherlands Canc Inst, Div Mol Pathol, Amsterdam, Netherlands.
EM mk.schmidt@nki.nl
RI Hartikainen, Jaana/E-6256-2015; Brenner, Hermann/B-4627-2017;
OI Brenner, Hermann/0000-0002-6129-1572; Shelling,
Andrew/0000-0002-5300-1934; Phillips, Kelly-Anne/0000-0002-0475-1771;
Giles, Graham/0000-0003-4946-9099; Winship, Ingrid/0000-0001-8535-6003
FU Cancer Research UK [C1287/A10118, C1287/A12014, C490/A10124,
C490/A10119, C490/A16561]; UK National Institute for Health Research
Biomedical Research Centre at the University of Cambridge; BIHR
Biomedical Research Centre at the University of Cambridge; Dutch Cancer
Society [NKI 2007-3839, 2009-4363, DDHK 2004-3124, DDHK 2009-4318];
Baden Wurttemberg Ministry of Science, Research and Arts, Helsinki
University Central Hospital Research Fund, Academy of Finland [266528];
Finnish Cancer Society; Nordic Cancer Union; Sigrid Juselius Foundation;
Special Government Funding (FVO) of Kuopio University Hospital grants;
Cancer Fund of North Savo; Finnish Cancer Organizations; Australia
National Breast Cancer Foundation; National Health and Medical Research
Council (NHMRC); Queensland Cancer Fund; Cancer Foundation of Western
Australia; NIH [CA128978, CA116167, CA176785]; NIH Specialized Program
of Research Excellence (SPORE) in Breast Cancer [CA116201]; Breast
Cancer Research Foundation; David F and Margaret T Grohne Family
Foundation; Ting Tsung and Wei Fong Chao Foundation; Intramural Research
Funds of the National Cancer Institute; Department of Health and Human
Services, USA; CAPES Foundation; National Breast Cancer Foundation
Practitioner Fellowship; Cancer Council of New South Wales; Cancer
Council of Victoria; Cancer Council of Tasmania; Cancer Council of South
Australia
FX Cancer Research UK (C1287/A10118, C1287/A12014, C490/A10124, C490/A10119
and C490/A16561), the UK National Institute for Health Research
Biomedical Research Centre at the University of Cambridge; BIHR
Biomedical Research Centre at the University of Cambridge; Dutch Cancer
Society (grants NKI 2007-3839, 2009-4363; DDHK 2004-3124, DDHK
2009-4318); Baden Wurttemberg Ministry of Science, Research and Arts,
Helsinki University Central Hospital Research Fund, Academy of Finland
(266528), the Finnish Cancer Society, the Nordic Cancer Union and the
Sigrid Juselius Foundation, Special Government Funding (FVO) of Kuopio
University Hospital grants, Cancer Fund of North Savo, the Finnish
Cancer Organizations, Australia National Breast Cancer Foundation,
National Health and Medical Research Council (NHMRC), the Queensland
Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania
and South Australia, the Cancer Foundation of Western Australia, NIH
grants (CA128978, CA116167, CA176785), NIH Specialized Program of
Research Excellence (SPORE) in Breast Cancer (CA116201), the Breast
Cancer Research Foundation, the David F and Margaret T Grohne Family
Foundation, the Ting Tsung and Wei Fong Chao Foundation, Intramural
Research Funds of the National Cancer Institute, Department of Health
and Human Services, USA and CAPES Foundation. KAP is supported by a
National Breast Cancer Foundation Practitioner Fellowship.
NR 49
TC 4
Z9 4
U1 0
U2 12
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1741-7015
J9 BMC MED
JI BMC Med.
PD JUL 2
PY 2015
VL 13
DI 10.1186/s12916-015-0392-6
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA CL9QA
UT WOS:000357312000001
PM 26137966
ER
PT J
AU Liu, SB
Lu, GJ
Ali, S
Liu, WP
Zheng, L
Dai, HF
Li, HZ
Xu, H
Hua, YJ
Zhou, YJ
Ortega, J
Li, GM
Kunkel, TA
Shen, BH
AF Liu, Songbai
Lu, Guojun
Ali, Shafat
Liu, Wenpeng
Zheng, Li
Dai, Huifang
Li, Hongzhi
Xu, Hong
Hua, Yuejin
Zhou, Yajing
Ortega, Janice
Li, Guo-Min
Kunkel, Thomas A.
Shen, Binghui
TI Okazaki fragment maturation involves alpha-segment error editing by the
mammalian FEN1/MutS alpha functional complex
SO EMBO JOURNAL
LA English
DT Article
DE DNA mismatch repair; flap endonuclease 1; MutS alpha; Okazaki fragment
maturation; alpha-segment error editing
ID DNA-POLYMERASE-ALPHA; HUMAN FLAP ENDONUCLEASE-1; RNA PRIMER REMOVAL;
MISMATCH REPAIR; REPLICATION FIDELITY; MUTATION AVOIDANCE;
SUBSTRATE-BINDING; FEN1 MUTATIONS; IN-VITRO; EXONUCLEASE
AB During nuclear DNA replication, proofreading-deficient DNA polymerase alpha(Pol alpha) initiates Okazaki fragment synthesis with lower fidelity than bulk replication by proofreading-proficient Pol delta or Pol epsilon. Here, we provide evidence that the exonuclease activity of mammalian flap endonuclease (FEN1) excises Pol alpha replication errors in a MutS alpha-dependent, MutL alpha-independent mismatch repair process we call Pol alpha-segment error editing (AEE). We show that MSH2 interacts with FEN1 and facilitates its nuclease activity to remove mismatches near the 5' ends of DNA substrates. Mouse cells and mice encoding FEN1 mutations display AEE deficiency, a strong mutator phenotype, enhanced cellular transformation, and increased cancer susceptibility. The results identify a novel role for FEN1 in a specialized mismatch repair pathway and a new cancer etiological mechanism.
C1 [Liu, Songbai; Liu, Wenpeng; Xu, Hong; Hua, Yuejin] Zhejiang Univ, Coll Life Sci, Hangzhou 310003, Zhejiang, Peoples R China.
[Liu, Songbai; Liu, Wenpeng; Xu, Hong; Hua, Yuejin] Zhejiang Univ, Coll Agr & Biotechnol, Hangzhou 310003, Zhejiang, Peoples R China.
[Liu, Songbai; Lu, Guojun; Ali, Shafat; Liu, Wenpeng; Zheng, Li; Dai, Huifang; Li, Hongzhi; Shen, Binghui] City Hope Natl Med Ctr, Dept Radiat Biol, Duarte, CA 91010 USA.
[Liu, Songbai; Lu, Guojun; Ali, Shafat; Liu, Wenpeng; Zheng, Li; Dai, Huifang; Li, Hongzhi; Shen, Binghui] City Hope Natl Med Ctr, Dept Mol Med, Duarte, CA 91010 USA.
[Liu, Songbai; Lu, Guojun; Ali, Shafat; Liu, Wenpeng; Zheng, Li; Dai, Huifang; Li, Hongzhi; Shen, Binghui] City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA.
[Zhou, Yajing] Jiangsu Univ, Inst Life Sci, Zhen Jiang, Jiangsu, Peoples R China.
[Ortega, Janice; Li, Guo-Min] Univ Kentucky, Grad Ctr Toxicol, Markey Canc Ctr, Coll Med, Lexington, KY 40536 USA.
[Kunkel, Thomas A.] NIEHS, Genome Integr & Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
RP Shen, BH (reprint author), City Hope Natl Med Ctr, Dept Radiat Biol, 1500 E Duarte Rd, Duarte, CA 91010 USA.
EM bshen@coh.org
OI Li, Guo-Min/0000-0002-9842-4578
FU City of Hope Pathology, Bioinformatics and Integrated Genomics Core
facilities, NCI Designated Cancer Center Support Grant [P30 CA033572];
NIH [RO1 CA076734]; National Natural Science Foundation of China
[31370790]; Division of Intramural Research of the National Institutes
of Health, National Institute of Environmental Health Sciences [Z01
ES065089]; international corporation grant from National Natural
Sciences Foundation of China [31210103904]
FX We thank the City of Hope Pathology, Bioinformatics and Integrated
Genomics Core facilities, NCI Designated Cancer Center Support Grant P30
CA033572, Steven Vonderfecht D.V.M., Ph.D., for technical assistance
with characterization of the mouse cancer specimens, Liya Gu, Ph.D., for
her generous gift of the purified recombinant EXO1 protein, and Nancy
Linford, Ph.D., for her critical reading and editing of the manuscript.
The work was supported by an NIH Grant RO1 CA076734 to B.H.S., a
National Natural Science Foundation of China Grant 31370790 to Y.J.Z.,
and in part by Project Z01 ES065089 to TAK from the Division of
Intramural Research of the National Institutes of Health, National
Institute of Environmental Health Sciences, and an international
corporation grant from National Natural Sciences Foundation of China
(31210103904) to Y.J.H.
NR 48
TC 5
Z9 5
U1 3
U2 21
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0261-4189
EI 1460-2075
J9 EMBO J
JI Embo J.
PD JUL 2
PY 2015
VL 34
IS 13
BP 1829
EP 1843
DI 10.15252/embj.201489865
PG 15
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CL9UR
UT WOS:000357324100010
PM 25921062
ER
PT J
AU Rende, F
Cavallari, I
Andresen, V
Valeri, VW
D'Agostino, DM
Franchini, G
Ciminale, V
AF Rende, Francesca
Cavallari, Ilaria
Andresen, Vibeke
Valeri, Valerio W.
D'Agostino, Donna M.
Franchini, Genoveffa
Ciminale, Vincenzo
TI Identification of novel monocistronic HTLV-1 mRNAs encoding functional
Rex isoforms
SO RETROVIROLOGY
LA English
DT Article
DE HTLV-1; Rex; Splicing
ID IMMUNODEFICIENCY-VIRUS TYPE-1; GENE-EXPRESSION; PROTEIN; RETROVIRUSES;
REGION; CELLS
AB Background: Human T cell leukemia virus type 1 (HTLV-1) gene expression is controlled by the key regulatory proteins Tax and Rex. The concerted action of these proteins results in a two-phase kinetics of viral expression that depends on a time delay between their action. However, it is difficult to explain this delay, as Tax and Rex are produced from the same mRNA. In the present study we investigated whether HTLV-1 may produce novel mRNA species capable of expressing Rex and Tax independently.
Findings: Results revealed the expression of three alternatively spliced transcripts coding for novel Rex isoforms in infected cell lines and in primary samples from infected patients. One mRNA coded for a Tax isoform and a Rex isoform, and two mRNAs coded for Rex isoforms but not Tax. Functional assays showed that these Rex isoforms exhibit activity comparable to canonic Rex. An analysis of the temporal expression of these transcripts upon ex vivo culture of cells from infected patients and cell lines transfected with a molecular clone of HTLV-1 revealed early expression of the dicistronic tax/rex mRNAs followed by the monocistronic mRNAs coding for Rex isoforms.
Conclusion: The production of monocistronic HTLV-1 mRNAs encoding Rex isoforms with comparable activity to canonical Rex, but with distinct timing, would support a prolonged duration of Rex function with gradual loss of Tax, and is consistent with the two-phase expression kinetics. A thorough understanding of these regulatory circuits will shed light on the basis of viral latency and provide groundwork to develop strategies for eradicating persistent infections.
C1 [Rende, Francesca; Cavallari, Ilaria; Ciminale, Vincenzo] Univ Padua, Dept Surg Oncol & Gastroenterol, Padua, Italy.
[Andresen, Vibeke; Valeri, Valerio W.; Franchini, Genoveffa] NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA.
[D'Agostino, Donna M.] Univ Padua, Dept Biomed Sci, Padua, Italy.
[Ciminale, Vincenzo] IRCCS, Ist Oncol Veneto, Padua, Italy.
RP Ciminale, V (reprint author), Univ Padua, Dept Surg Oncol & Gastroenterol, Padua, Italy.
EM v.ciminale@unipd.it
OI Cavallari, Ilaria/0000-0002-7430-9137
FU Associazione Italiana per la Ricerca sul Cancro (AIRC) [4175, 13378];
AIRC-Cariverona Regional Grant; University of Padua [CPDA124913/12]
FX We thank Luigi Chieco-Bianchi for discussions and Charles Bangham and
Graham Taylor for discussions and patient samples. The research was
supported by investigator Grants from the Associazione Italiana per la
Ricerca sul Cancro (AIRC; nos. 4175 and 13378), an AIRC-Cariverona
Regional Grant, and the University of Padua (Ateneo Grant no.
CPDA124913/12).
NR 22
TC 2
Z9 2
U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-4690
J9 RETROVIROLOGY
JI Retrovirology
PD JUL 2
PY 2015
VL 12
AR 58
DI 10.1186/s12977-015-0184-2
PG 7
WC Virology
SC Virology
GA CL7KE
UT WOS:000357150100001
PM 26133546
ER
PT J
AU Gershon, AA
Breuer, J
Cohen, JI
Cohrs, RJ
Gershon, MD
Gilden, D
Grose, C
Hambleton, S
Kennedy, PGE
Oxman, MN
Seward, JF
Yamanishi, K
AF Gershon, Anne A.
Breuer, Judith
Cohen, Jeffrey I.
Cohrs, Randall J.
Gershon, Michael D.
Gilden, Don
Grose, Charles
Hambleton, Sophie
Kennedy, Peter G. E.
Oxman, Michael N.
Seward, Jane F.
Yamanishi, Koichi
TI Varicella zoster virus infection
SO NATURE REVIEWS DISEASE PRIMERS
LA English
DT Article
ID HERPES-SIMPLEX-VIRUS; HUMAN TRIGEMINAL GANGLIA; PLACEBO-CONTROLLED
TRIAL; STEM-CELL TRANSPLANTATION; SUBUNIT CANDIDATE VACCINE;
POLYMERASE-CHAIN-REACTION; POSTHERPETIC NEURALGIA; UNITED-STATES;
HEALTHY-CHILDREN; NERVOUS-SYSTEM
AB Infection with varicella zoster virus (VZV) causes varicella (chickenpox), which can be severe in immunocompromised individuals, infants and adults. Primary infection is followed by latency in ganglionic neurons. During this period, no virus particles are produced and no obvious neuronal damage occurs. Reactivation of the virus leads to virus replication, which causes zoster (shingles) in tissues innervated by the involved neurons, inflammation and cell death -a process that can lead to persistent radicular pain (postherpetic neuralgia). The pathogenesis of postherpetic neuralgia is unknown and it is difficult to treat. Furthermore, other zoster complications can develop, including myelitis, cranial nerve palsies, meningitis, stroke (vasculopathy), retinitis, and gastroenterological infections such as ulcers, pancreatitis and hepatitis. VZV is the only human herpesvirus for which highly effective vaccines are available. After varicella or vaccination, both wild-type and vaccine-type VZV establish latency, and long-term immunity to varicella develops. However, immunity does not protect against reactivation. Thus, two vaccines are used: one to prevent varicella and one to prevent zoster. In this Primer we discuss the pathogenesis, diagnosis, treatment, and prevention of VZV infections, with an emphasis on the molecular events that regulate these diseases. For an illustrated summary of this Primer, visit: http://go.nature.com/14xVI1
C1 [Gershon, Anne A.] Columbia Univ Coll Phys & Surg, 630 West 168th St, New York, NY 10032 USA.
[Breuer, Judith] UCL, Dept Infect & Immun, London WC1E 6BT, England.
[Cohen, Jeffrey I.] NIAID, Med Virol Sect, Infect Dis Lab, NIH, Bethesda, MA USA.
[Cohrs, Randall J.; Gilden, Don] Univ Colorado, Sch Med, Dept Neurol, Aurora, CO USA.
[Cohrs, Randall J.; Gilden, Don] Univ Colorado, Sch Med, Dept Microbiol & Immunol, Aurora, CO USA.
[Gershon, Michael D.] Columbia Univ Coll Phys & Surg, Dept Pathol & Cell Biol, New York, NY 10032 USA.
[Grose, Charles] Univ Iowa, Childrens Hosp, Div Infect Diseases Virol, Iowa City, IA USA.
[Hambleton, Sophie] Newcastle Univ, Sch Med, Inst Cellular Med, Primary Immunodeficiency Grp, Newcastle Upon Tyne, Tyne & Wear, England.
[Kennedy, Peter G. E.] Univ Glasgow, Inst Neurol Sci, Southern Gen Hosp, Dept Neurol, Glasgow, Lanark, Scotland.
[Oxman, Michael N.] Univ Calif San Diego, Sch Med, Vet Affairs San Diego Healthcare Syst, Infect Dis Sect,Med Serv,Div Infect Dis,Dept Med, San Diego, CA 92103 USA.
[Seward, Jane F.] Ctr Dis Control & Prevent, Div Viral Dis, Natl Ctr Immunizat & Resp Dis, CDC, Atlanta, GA USA.
[Yamanishi, Koichi] Osaka Univ, Res Fdn Microbial Dis, Suita, Osaka, Japan.
RP Gershon, AA (reprint author), Columbia Univ Coll Phys & Surg, 630 West 168th St, New York, NY 10032 USA.
EM aag1@cumc.columbia.edu
FU National Institute for Health Research (NIHR) University College London
(UCL)/University College London Hospitals NHS Foundation Trust (UCLH)
Biomedical Research Centre, UK; National Institute of Allergy and
Infectious Diseases, USA; US National Institutes of Health (NIH)
[NS082228, AG032958]; NIH [AG032958, AG006127, AI89716, DK 09394]; Sir
Jules Thorn Charitable Trust; James R. and Jesse V. Scott Fund for
Shingles Research in the Veterans Medical Research Foundation; Wellcome
Trust
FX J.B. receives funding from the National Institute for Health Research
(NIHR) University College London (UCL)/University College London
Hospitals NHS Foundation Trust (UCLH) Biomedical Research Centre, UK.
J.I.C. is supported by the intramural research program of the National
Institute of Allergy and Infectious Diseases, USA. R.J.C. is supported
by grants NS082228 and AG032958 from the US National Institutes of
Health (NIH). D.G. is supported by grants AG006127 and AG032958 from the
NIH. C.G. is supported by grant AI89716 from the NIH. S.H. receives
funding from the Sir Jules Thorn Charitable Trust. M.D.G. and A.A.G.
receive funding from NIH R01 Grant DK 09394. M.N.O.'s work is partially
supported by the James R. and Jesse V. Scott Fund for Shingles Research
in the Veterans Medical Research Foundation. P.G.E.K. receives grant
funding for research from the Wellcome Trust.
NR 211
TC 5
Z9 5
U1 8
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2056-676X
J9 NAT REV DIS PRIMERS
JI Nat. Rev. Dis. Primers
PD JUL 2
PY 2015
VL 1
AR 15016
DI 10.1038/nrdp.2015.16
PG 18
WC Medicine, General & Internal
SC General & Internal Medicine
GA DT2KN
UT WOS:000381309300001
PM 27188665
ER
PT J
AU Richter, HE
Nager, CW
Burgio, KL
Whitworth, R
Weidner, AC
Schaffer, J
Zyczynski, HM
Norton, P
Jelovsek, JE
Meikle, SF
Spino, C
Gantz, M
Graziano, S
Brubaker, L
AF Richter, Holly E.
Nager, Charles W.
Burgio, Kathryn L.
Whitworth, Ryan
Weidner, Alison C.
Schaffer, Joseph
Zyczynski, Halina M.
Norton, Peggy
Jelovsek, John Eric
Meikle, Susan F.
Spino, Cathie
Gantz, Marie
Graziano, Scott
Brubaker, Linda
CA NICHD Pelvic Floor Disorders Netwo
TI Incidence and Predictors of Anal Incontinence After Obstetric Anal
Sphincter Injury in Primiparous Women
SO FEMALE PELVIC MEDICINE AND RECONSTRUCTIVE SURGERY
LA English
DT Article
DE fecal incontinence; obstetric anal sphincter injury; fecal urgency; anal
incontinence
ID RANDOMIZED CLINICAL-TRIAL; VAGINAL DELIVERY; URINARY-INCONTINENCE; FECAL
INCONTINENCE; RACIAL-DIFFERENCES; PRIMARY REPAIR; RISK-FACTORS;
LACERATIONS; PREVALENCE; DISRUPTION
AB Objective
This study aimed to describe the incidence of fecal incontinence (FI) at 6, 12, and 24 weeks postpartum; anal incontinence (AI) and fecal urgency at 24 weeks; and identify predictors of AI in women with obstetric anal sphincter injury (OASI).
Methods
Primiparous women sustaining OASIs were identified at 8 clinical sites. Third-degree OASIs were characterized using World Health Organization criteria, 3a (<50%) or 3b (>50%) tear through the sphincter. Fecal incontinence was defined as leakage of liquid/solid stool and/or mucus in the past month; AI was defined as leakage of liquid/solid stool and/or mucus and/or gas in the past month and was assessed at 6, 12, and 24 weeks postpartum using the Fecal Incontinence Severity Index. Logistic regression identified variables associated with AI.
Results
Three hundred forty-three women participated: 297 subjects sustained a third-degree OASI, 168 type 3a, 98 type 3b and 31 indeterminant; 45 had a fourth-degree OASI. Overall FI incidence at 6, 12, and 24 weeks was 7% [23/326; 95% confidence interval (CI), 4%-10%], 4% (6/145; 95% CI, 2%-9%), and 9% (13/138; 95% CI, 5%-16%), respectively. At 24 weeks, AI incidence was 24% (95% CI, 17%-32%) and fecal urgency 21% (95% CI, 15%-29%). No significant differences in FI and AI rates were noted by third-degree type or between groups with third and fourth OASI. Flatal incontinence was greater in women sustaining a fourth-degree tear (35% vs 16%, P = 0.04). White race (adjusted odds ratio, 4.64; 95% CI, 1.35-16.02) and shorter duration of second stage (adjusted odds ratio, 1.47 per 30 minute decrease; 95% CI, 1.12-1.92) were associated with AI at 24 weeks.
Conclusions
Overall 24-week incidence of FI is 9% (95% CI, 5%-16%) and AI is 24% (95% CI, 17%-32%). In women with OASI, white race and shorter second-stage labor were associated with postpartum AI.
Clinical Trial Registration: NCT01166399 (
[GRAPHICS]
)
C1 [Richter, Holly E.] Univ Alabama Birmingham, Dept Obstet & Gynecol, 1700 6th Ave South,Suite 10382, Birmingham, AL 35294 USA.
[Nager, Charles W.] Univ Calif San Diego, Dept Obstet & Gynecol, San Diego, CA 92103 USA.
[Burgio, Kathryn L.] Vet Adm GRECC, Dept Gerontol Geriatr & Pallat Care, Birmingham, AL USA.
[Whitworth, Ryan; Gantz, Marie] Res Triangle Inst, Res Triangle Pk, NC 27709 USA.
[Weidner, Alison C.] Duke Univ, Dept Obstet & Gynecol, Durham, NC USA.
[Schaffer, Joseph] SW Texas State Univ, Dept Obstet & Gynecol, Dallas, TX USA.
[Zyczynski, Halina M.] Univ Pittsburgh, Magee Womens Res Inst, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA.
[Norton, Peggy] Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA.
[Jelovsek, John Eric] Cleveland Clin, Dept Obstet & Gynecol, Cleveland, OH 44106 USA.
[Meikle, Susan F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Spino, Cathie] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
[Graziano, Scott; Brubaker, Linda] Loyola Univ, Dept Obstet & Gynecol, Chicago, IL 60611 USA.
RP Richter, HE (reprint author), Univ Alabama Birmingham, Dept Obstet & Gynecol, 1700 6th Ave South,Suite 10382, Birmingham, AL 35294 USA.
EM hrichter@uabmc.edu
FU Pelvalon; NIDDK [U01DK060380, K24DK68389]; Boston Scientific; Eunice
Kennedy Shriver National Institute of Child Health and Human Development
(Duke) [2-U10-HD04267-12]; NIH Office of Research on Women's Health;
Eunice Kennedy Shriver National Institute of Child Health and Human
Development (Loyola) [U10-HD041250]; Eunice Kennedy Shriver National
Institute of Child Health and Human Development (UAB)
[2-U10-HD041261-11]; Eunice Kennedy Shriver National Institute of Child
Health and Human Development (Utah) [U10-HD054136]; Eunice Kennedy
Shriver National Institute of Child Health and Human Development
(Cleveland Clinic) [2-U10-HD054215-06]; Eunice Kennedy Shriver National
Institute of Child Health and Human Development (UCSD)
[2-U10-HD054214-06]; Eunice Kennedy Shriver National Institute of Child
Health and Human Development (Pittsburgh) [1-U10-HD069006-01]; Eunice
Kennedy Shriver National Institute of Child Health and Human Development
(UTSW) [2-U10-HD054241-06]; Eunice Kennedy Shriver National Institute of
Child Health and Human Development (University of Michigan)
[U01-HD41249]; Eunice Kennedy Shriver National Institute of Child Health
and Human Development (RTI) [1-U01-HD069031-01]
FX Dr Richter is a member of Board of Directors in Society of Gynecologic
Surgeons, received research grant from Pelvalon (grant number: N/A) and
NIDDK (U01DK060380 and K24DK68389), is a Consultant for Pelvalon, and
received royalties from UpToDate. Dr Nager is a member of the Board of
Directors at American Urogynecologic Society, received honoraria for
lectures at Symposia Medicus, and received royalties from UpToDate. Dr
Schaffer is a consultant for Astellas Pharmaceuticals, Cadence
Pharmaceuticals, Ferring Pharmaceuticals, and received research funding
Boston Scientific and honoraria as a speaker for Astellas
Pharmaceuticals, Cadence Pharmaceuticals, received royalties from
McGraw-Hill. Dr Zyczynski is a consultant for Key Technologies. None of
the other authors report a conflict of interest.; Supported by grants
from The Eunice Kennedy Shriver National Institute of Child Health and
Human Development (Duke: 2-U10-HD04267-12, Loyola: U10-HD041250, UAB:
2-U10-HD041261-11, Utah: U10-HD054136, Cleveland Clinic:
2-U10-HD054215-06, UCSD: 2-U10-HD054214-06, Pittsburgh:
1-U10-HD069006-01, UTSW: 2-U10-HD054241-06, University of Michigan:
U01-HD41249, RTI: 1-U01-HD069031-01) and the NIH Office of Research on
Women's Health
NR 23
TC 6
Z9 6
U1 3
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 2151-8378
EI 2154-4212
J9 FEMALE PELVIC MED RE
JI Female Pelvic Med. Reconstr. Surg.
PD JUL-AUG
PY 2015
VL 21
IS 4
BP 182
EP 189
DI 10.1097/SPV.0000000000000160
PG 8
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA DI4CT
UT WOS:000373448600002
PM 25679358
ER
PT J
AU Straughan, DM
Kerkar, S
Azoury, SC
Reardon, ES
Schrump, DS
AF Straughan, David M.
Kerkar, Sid
Azoury, Said C.
Reardon, Emily S.
Schrump, David S.
TI Pulmonary mucosa-associated lymphoma in a patient with von Hippel-Lindau
disease
SO JOURNAL OF SURGICAL CASE REPORTS
LA English
DT Article
ID VHL GENE
AB A 61-year-old female with a past medical history significant for von Hippel-Lindau (VHL) syndrome presented with multiple bilateral pulmonary lesions found on surveillance computed tomography scan. Positron emission tomography demonstrated avidity in a lesion in the right upper lobe. After an equivocal biopsy, a lobectomy via a thoracoscopic approach was performed as this lesion was concerning for a primary lung cancer. Pathology revealed a diagnosis of pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma. To our knowledge, this is the first reported case of a pulmonary MALT lymphoma in a patient with VHL.
C1 [Straughan, David M.; Azoury, Said C.; Reardon, Emily S.; Schrump, David S.] NCI, Dept Thorac & GI Oncol, NIH, Bethesda, MD 20892 USA.
[Kerkar, Sid] NCI, Dept Pathol, NIH, Bethesda, MD 20892 USA.
RP Straughan, DM (reprint author), 10 Ctr Dr,Room 4-3940, Bethesda, MD 20892 USA.
EM david.m.straughan@gmail.com
NR 8
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 2042-8812
J9 J SURG CASE REP
JI J. Surg. Case Rep.
PD JUL
PY 2015
IS 7
DI 10.1093/jscr/rjv080
PG 4
WC Surgery
SC Surgery
GA DH2DH
UT WOS:000372593900014
ER
PT J
AU Hoskins, JW
Ibrahim, A
Emmanuel, M
Parikh, H
Jia, JP
Collins, I
Ylaya, K
Altekruse, SF
Hewitt, SM
Petersen, GM
Amundadottir, LT
AF Hoskins, Jason W.
Ibrahim, Abdisamad
Emmanuel, Mickey
Parikh, Hemang
Jia, Jinping
Collins, Irene
Ylaya, Kris
Altekruse, Sean F.
Hewitt, Stephen M.
Petersen, Gloria M.
Amundadottir, Laufey T.
TI Functional analysis of the chr13q22.1 pancreatic cancer risk locus
suggests allele-specific effects on DIS3 expression with prognostic
implications
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT AACR Special Conference on Pancreatic Cancer - Innovations in Research
and Treatment
CY MAY 18-21, 2014-2015
CL New Orleans, LA
SP Amer Assoc Canc Res
C1 [Hoskins, Jason W.; Ibrahim, Abdisamad; Emmanuel, Mickey; Parikh, Hemang; Jia, Jinping; Collins, Irene; Ylaya, Kris; Altekruse, Sean F.; Hewitt, Stephen M.; Amundadottir, Laufey T.] NCI, Bethesda, MD 20892 USA.
[Petersen, Gloria M.] Mayo Clin, Rochester, MN USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD JUL 1
PY 2015
VL 75
SU 13
MA B111
PG 1
WC Oncology
SC Oncology
GA DF3RL
UT WOS:000371263900097
ER
PT J
AU Hoskins, JW
Flandez, M
Jia, JP
Parikh, H
Collins, I
Emmanuel, M
Ibrahim, A
Xiao, WM
Powell, J
Malats, N
Petersen, GM
Real, FX
Amundadottir, LT
AF Hoskins, Jason W.
Flandez, Marta
Jia, Jinping
Parikh, Hemang
Collins, Irene
Emmanuel, Mickey
Ibrahim, Abdisamad
Xiao, Wenming
Powell, John
Malats, Nuria
Petersen, Gloria M.
Real, Fransisco X.
Amundadottir, Laufey T.
TI Transcriptome analysis in pancreatic cancer reveals a tumor suppressor
function for HNF1A
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT AACR Special Conference on Pancreatic Cancer - Innovations in Research
and Treatment
CY MAY 18-21, 2014-2015
CL New Orleans, LA
SP Amer Assoc Canc Res
C1 [Hoskins, Jason W.; Jia, Jinping; Parikh, Hemang; Collins, Irene; Emmanuel, Mickey; Ibrahim, Abdisamad] NCI, Bethesda, MD 20892 USA.
[Flandez, Marta; Malats, Nuria; Real, Fransisco X.] CNIO Spanish Natl Canc Res Ctr, Madrid, Spain.
[Xiao, Wenming; Powell, John] NIH, Bethesda, MD 20892 USA.
[Petersen, Gloria M.] Mayo Clin, Rochester, MN USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD JUL 1
PY 2015
VL 75
SU 13
MA B112
DI 10.1158/1538-7445.PANCA2014-B112
PG 1
WC Oncology
SC Oncology
GA DF3RL
UT WOS:000371263900098
ER
PT J
AU Mezhir, JJ
O'Leary, BR
Bellizzi, AM
Altekruse, S
Lynch, CF
Hernandez, BY
Cozen, W
Henry, MD
Keene, J
Beardsley, RA
Spitz, DR
Domann, FE
AF Mezhir, James J.
O'Leary, Brianne R.
Bellizzi, Andrew M.
Altekruse, Sean
Lynch, Charles F.
Hernandez, Brenda Y.
Cozen, Wendy
Henry, Michael D.
Keene, Jeffrey
Beardsley, Robert A.
Spitz, Douglas R.
Domann, Frederick E.
TI The role of extracellular superoxide dismutase activity in pancreatic
cancer biology and therapy
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT AACR Special Conference on Pancreatic Cancer - Innovations in Research
and Treatment
CY MAY 18-21, 2014-2015
CL New Orleans, LA
SP Amer Assoc Canc Res
C1 [Mezhir, James J.; O'Leary, Brianne R.; Bellizzi, Andrew M.; Lynch, Charles F.; Henry, Michael D.; Spitz, Douglas R.; Domann, Frederick E.] Univ Iowa, Iowa City, IA USA.
[Altekruse, Sean] NIH, Bethesda, MD 20892 USA.
[Hernandez, Brenda Y.] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
[Cozen, Wendy] Univ So Calif, Los Angeles, CA USA.
[Keene, Jeffrey; Beardsley, Robert A.] Galera Therapeut, Malvern, PA USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
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 JUL 1
PY 2015
VL 75
SU 13
MA B52
DI 10.1158/1538-7445.PANCA2014-B52
PG 2
WC Oncology
SC Oncology
GA DF3RL
UT WOS:000371263900132
ER
PT J
AU Naranjo-Suarez, S
Callen, E
Zhong, Y
Makohon-Moore, A
Nussenzweig, A
Iacobuzio-Donahue, C
AF Naranjo-Suarez, Salvador
Callen, Elsa
Zhong, Yi
Makohon-Moore, Alvin
Nussenzweig, Andre
Iacobuzio-Donahue, Christine
TI Hypoxia-induced CHK1 repression may enhance the mutator phenotype of
pancreatic cancer cells
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT AACR Special Conference on Pancreatic Cancer - Innovations in Research
and Treatment
CY MAY 18-21, 2014-2015
CL New Orleans, LA
SP Amer Assoc Canc Res
C1 [Naranjo-Suarez, Salvador; Zhong, Yi; Makohon-Moore, Alvin] Johns Hopkins Med Inst, Baltimore, MD 21205 USA.
[Callen, Elsa; Nussenzweig, Andre] NIH, Bethesda, MD 20892 USA.
[Iacobuzio-Donahue, Christine] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD JUL 1
PY 2015
VL 75
SU 13
MA A68
DI 10.1158/1538-7445.PANCA2014-A68
PG 2
WC Oncology
SC Oncology
GA DF3RL
UT WOS:000371263900062
ER
PT J
AU Poplin, EA
August, DA
Moss, RA
Ben-Menachem, T
Michael, H
Repaka, A
Artymyshyn, R
Chan, C
Gulley, JL
DiPaola, RS
Lattime, EC
AF Poplin, Elizabeth A.
August, David A.
Moss, Rebecca A.
Ben-Menachem, Tamir
Michael, Hazar
Repaka, Aparna
Artymyshyn, Renee
Chan, Chang
Gulley, James L.
DiPaola, Robert S.
Lattime, Edmund C.
TI Panvac-F and Panvac-V: Phase I study of intratumoral and systemic
vaccination
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT AACR Special Conference on Pancreatic Cancer - Innovations in Research
and Treatment
CY MAY 18-21, 2014-2015
CL New Orleans, LA
SP Amer Assoc Canc Res
C1 [Poplin, Elizabeth A.; August, David A.; Moss, Rebecca A.; Chan, Chang; DiPaola, Robert S.; Lattime, Edmund C.] Rutgers Canc Inst New Jersey, New Brunswick, NJ USA.
[Ben-Menachem, Tamir; Michael, Hazar] Summit Med Grp, Summit, NJ USA.
[Repaka, Aparna; Artymyshyn, Renee] Rutgers Robert Wood Johnson Med Sch, New Brunswick, NJ USA.
[Gulley, James L.] NIH, Bethesda, MD 20892 USA.
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER 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 JUL 1
PY 2015
VL 75
SU 13
MA B100
DI 10.1158/1538-7445.PANCA2014-B100
PG 2
WC Oncology
SC Oncology
GA DF3RL
UT WOS:000371263900091
ER
PT J
AU Vietsch, EE
Simmons, JK
Peran, I
Stenstra, M
Mock, BA
Wellstein, A
AF Vietsch, Eveline E.
Simmons, John K.
Peran, Ivana
Stenstra, Marianne
Mock, Beverly A.
Wellstein, Anton
TI De-convoluting therapeutic resistance in a pancreatic cancer model:
Pharmacogenomic evaluation of intratumoral clonal heterogeneity
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT AACR Special Conference on Pancreatic Cancer - Innovations in Research
and Treatment
CY MAY 18-21, 2014-2015
CL New Orleans, LA
SP Amer Assoc Canc Res
C1 [Vietsch, Eveline E.; Peran, Ivana; Stenstra, Marianne; Wellstein, Anton] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA.
[Simmons, John K.; Mock, Beverly A.] NCI, 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 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD JUL 1
PY 2015
VL 75
SU 13
MA A73
DI 10.1158/1538-7445.PANCA2014-A73
PG 1
WC Oncology
SC Oncology
GA DF3RL
UT WOS:000371263900067
ER
PT J
AU Goldstein, AB
Heinssen, RK
Azrin, ST
AF Goldstein, Amy B.
Heinssen, Robert K.
Azrin, Susan T.
TI Accelerating Science-to-Practice for Early Psychosis
SO PSYCHIATRIC SERVICES
LA English
DT Editorial Material
C1 [Goldstein, Amy B.; Heinssen, Robert K.; Azrin, Susan T.] NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA.
RP Goldstein, AB (reprint author), NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 JUL
PY 2015
VL 66
IS 7
BP 665
EP 665
DI 10.1176/appi.ps.660708
PG 1
WC Health Policy & Services; Public, Environmental & Occupational Health;
Psychiatry
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Psychiatry
GA DE5RO
UT WOS:000370689600001
PM 26130149
ER
PT J
AU Dixon, LB
Goldman, HH
Bennett, ME
Wang, YJ
McNamara, KA
Mendon, SJ
Goldstein, AB
Choi, CWJ
Lee, RJ
Lieberman, JA
Essock, SM
AF Dixon, Lisa B.
Goldman, Howard H.
Bennett, Melanie E.
Wang, Yuanjia
McNamara, Karen A.
Mendon, Sapna J.
Goldstein, Amy B.
Choi, Chien-Wen J.
Lee, Rufina J.
Lieberman, Jeffrey A.
Essock, Susan M.
TI Implementing Coordinated Specialty Care for Early Psychosis: The RAISE
Connection Program
SO PSYCHIATRIC SERVICES
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; 1ST EPISODE PSYCHOSIS; EARLY INTERVENTION
SERVICE; 1ST-EPISODE PSYCHOSIS; INDIVIDUAL PLACEMENT; MENTAL-HEALTH;
RECENT-ONSET; HONG-KONG; SCHIZOPHRENIA; SUPPORT
AB Objective: The RAISE (Recovery After an Initial Schizophrenia Episode) Connection Program Implementation and Evaluation Study developed tools necessary to implement and disseminate an innovative team-based intervention designed to promote engagement and treatment participation, foster recovery, and minimize disability among individuals experiencing early psychosis. This article describes the treatment model and reports on service utilization and outcomes. It was hypothesized that individuals' symptoms and functioning would improve over time.
Methods: A total of 65 individuals in RAISE Connection Program treatment across two sites (Baltimore and New York City) were enrolled and received services for up to two years. Primary outcomes, including social and occupational functioning and symptoms, were evaluated. Trajectories for individuals' outcomes over time were examined with linear and quadratic mixed-effects models with repeated measures.
Results: Measures of occupational and social functioning improved significantly over time, symptoms declined, and rates of remission improved. Visits were most frequent during the first three months, with a mean +/- SD of 23.2 +/- 11.5 unduplicated staff encounters per quarter. Such encounters decreased to 8.8 +/- 5.2 in the final quarter of year 2.
Conclusions: The overall project was successful in that the treatment program was delivered and tools useful to other clinical settings were produced. The strengths of this study lie in the demonstrated feasibility of delivering the coordinated specialty care model and the associated high rates of engagement among individuals who are typically difficult to engage in treatment. Notwithstanding the lack of a built-in comparison group, participant outcomes were promising, with improvements comparable to those seen with other successful interventions.
C1 [Dixon, Lisa B.; Mendon, Sapna J.; Choi, Chien-Wen J.; Lieberman, Jeffrey A.; Essock, Susan M.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
[Dixon, Lisa B.; Lieberman, Jeffrey A.; Essock, Susan M.] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY USA.
[Goldman, Howard H.; Bennett, Melanie E.; McNamara, Karen A.] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA.
[Wang, Yuanjia] Columbia Univ, Mailman Sch Publ Hlth, Div Biostat, New York, NY USA.
[Goldstein, Amy B.] NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA.
[Lee, Rufina J.] CUNY Hunter Coll, Silberman Sch Social Work, New York, NY 10021 USA.
RP Dixon, LB (reprint author), New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
EM dixonli@nyspi.columbia.edu
FU American Recovery and Reinvestment Act; National Institute of Mental
Health [HHSN271200900020C]; New York State Office of Mental Health;
Maryland Mental Hygiene Administration; Alkermes; Biomarin;
EnVivo/Forum; Genentech; Novartis; Sunovion
FX This project was funded in part with federal funds from the American
Recovery and Reinvestment Act of 2009, from the National Institute of
Mental Health under contract HHSN271200900020C (Dr. Dixon, principal
investigator), and from the New York State Office of Mental Health and
the Maryland Mental Hygiene Administration. The authors thank the RAISE
Connection Program investigators, RAISE clinicians and program staff,
and participants of the RAISE Connection Program.; Dr. Dixon, Ms.
Mendon, Dr. Lee, and Dr. Essock are offering training and consultation
to help others provide the type of first-episode psychosis services
described here. They do not expect to receive compensation for this
training other than that received as part of work done for their
employers. Dr. Lieberman serves on the advisory boards of Clintara,
Intracellular Therapies, and Pear Therapeutics and receives grant
support from Alkermes, Biomarin, EnVivo/Forum, Genentech, Novartis, and
Sunovion. He holds a financial interest in and a patent from Repligen.
The other authors report no financial relationships with commercial
interests.
NR 52
TC 15
Z9 15
U1 10
U2 13
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 JUL
PY 2015
VL 66
IS 7
BP 691
EP 698
DI 10.1176/appi.ps.201400281
PG 8
WC Health Policy & Services; Public, Environmental & Occupational Health;
Psychiatry
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Psychiatry
GA DE5RO
UT WOS:000370689600007
PM 25772764
ER
PT J
AU Lucksted, A
Essock, SM
Stevenson, J
Mendon, SJ
Nossel, IR
Goldman, HH
Goldstein, AB
Dixon, LB
AF Lucksted, Alicia
Essock, Susan M.
Stevenson, Jennifer
Mendon, Sapna J.
Nossel, Ilana R.
Goldman, Howard H.
Goldstein, Amy B.
Dixon, Lisa B.
TI Client Views of Engagement in the RAISE Connection Program for Early
Psychosis Recovery
SO PSYCHIATRIC SERVICES
LA English
DT Article
ID MENTAL-HEALTH; SCHIZOPHRENIA; DISENGAGEMENT; BARRIERS; STARS; CARE
AB Objective: This study assessed factors that facilitated or impeded clients' engagement in services offered by the Recovery After an Initial Schizophrenia Episode (RAISE) Connection Program for youths and young adults experiencing early psychosis. It was part of the larger RAISE Implementation and Engagement Study.
Methods: Thematic qualitative analyses of data from in-person, semistructured interviews with 32 clients were used to examine experiences of program services, staff practices, clients' engagement behaviors, and related factors, such as expectations, family involvement, illness, and setting. Eighteen clients were well engaged with services, and 14 were not. Thirteen were interviewed early in their program involvement (two to nine months after enrollment) and 18 others later (12 to 24 months after enrollment).
Results: Four domains of factors influenced engagement: individualized care, program attributes, family member engagement, and personal attributes. A central factor was the program's focus on clients' life goals. For many interviewees, engagement hinged substantially on receiving what could be considered nonclinical services, such as supported education and employment. Other key factors were individualized services and staff interactions that were respectful, warm, and flexible; engagement of family members; and a focus on shared decision making.
Conclusions: The findings help explain the Connection Program's effectiveness regarding client engagement and deepen understanding of treatment engagement for youths and young adults experiencing early psychosis. The individualized, flexible, recovery-focused, and assertive model of services and client-staff interaction, incorporating shared decision making and a focus on client life goals, should be implemented and sustained in services for this population.
C1 [Lucksted, Alicia; Stevenson, Jennifer; Goldman, Howard H.] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA.
[Essock, Susan M.; Mendon, Sapna J.; Nossel, Ilana R.; Dixon, Lisa B.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
[Essock, Susan M.; Nossel, Ilana R.; Dixon, Lisa B.] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA.
[Goldstein, Amy B.] NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA.
RP Lucksted, A (reprint author), Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA.
EM aluckste@psych.umaryland.edu
FU American Recovery and Reinvestment Act; National Institute of Mental
Health (NIMH) [HSN271200900020C]; New York State Office of Mental
Health; Maryland Mental Hygiene Administration
FX This project has been funded in part with federal funds from the
American Recovery and Reinvestment Act of 2009 and from the National
Institute of Mental Health (NIMH) under contract HSN271200900020C.
Additional support was provided by the New York State Office of Mental
Health and the Maryland Mental Hygiene Administration. The authors thank
the individuals who were interviewed for this project. The content is
solely the responsibility of the authors and does not necessarily
represent the official views of NIMH, the National Institutes of Health,
or the federal government.
NR 19
TC 2
Z9 2
U1 1
U2 9
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 JUL
PY 2015
VL 66
IS 7
BP 699
EP 704
DI 10.1176/appi.ps.201400475
PG 6
WC Health Policy & Services; Public, Environmental & Occupational Health;
Psychiatry
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Psychiatry
GA DE5RO
UT WOS:000370689600008
PM 25873029
ER
PT J
AU Addington, J
Heinssen, RK
Robinson, DG
Schooler, NR
Marcy, P
Brunette, MF
Correll, CU
Estroff, S
Mueser, KT
Penn, D
Robinson, JA
Rosenheck, RA
Azrin, ST
Goldstein, AB
Severe, J
Kane, JM
AF Addington, Jean
Heinssen, Robert K.
Robinson, Delbert G.
Schooler, Nina R.
Marcy, Patricia
Brunette, Mary F.
Correll, Christoph U.
Estroff, Sue
Mueser, Kim T.
Penn, David
Robinson, James A.
Rosenheck, Robert A.
Azrin, Susan T.
Goldstein, Amy B.
Severe, Joanne
Kane, John M.
TI Duration of Untreated Psychosis in Community Treatment Settings in the
United States
SO PSYCHIATRIC SERVICES
LA English
DT Article
ID 1ST-EPISODE SCHIZOPHRENIA; METAANALYSIS; EPISODE
AB Objective: This study is the first to examine duration of untreated psychosis (DUP) among persons receiving care in community mental health centers in the United States.
Methods: Participants were 404 individuals (ages 15-40) who presented for treatment for first-episode psychosis at 34 nonacademic clinics in 21 states. DUP and individual- and site-level variables were measured.
Results: Median DUP was 74 weeks (mean=193.5 +/- 262.2 weeks; 68% of participants had DUP of greater than six months). Correlates of longer DUP included earlier age at first psychotic symptoms, substance use disorder, positive and general symptom severity, poorer functioning, and referral from outpatient treatment settings.
Conclusions: This study reported longer DUP than studies conducted in academic settings but found similar correlates of DUP. Reducing DUP in the United States will require examination of factors in treatment delay in local service settings and targeted strategies for closing gaps in pathways to specialty FEP care.
C1 [Addington, Jean] Univ Calgary, Dept Psychiat, Calgary, AB, Canada.
[Heinssen, Robert K.; Azrin, Susan T.; Goldstein, Amy B.; Severe, Joanne] NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA.
[Robinson, Delbert G.; Correll, Christoph U.; Kane, John M.] Zucker Hillside Hosp, Dept Psychiat Res, Glen Oaks, NY USA.
[Marcy, Patricia] Zucker Hillside Hosp, Glen Oaks, NY USA.
[Marcy, Patricia] Feinstein Inst Med Res, Manhasset, NY USA.
[Schooler, Nina R.] Georgetown Univ, Sch Med, Dept Psychiat, Washington, DC USA.
[Brunette, Mary F.] Geisel Sch Med, Dept Psychiat, Lebanon, NH USA.
[Estroff, Sue] Univ N Carolina, Dept Social Med, Chapel Hill, NC USA.
[Penn, David] Univ N Carolina, Dept Psychol, Chapel Hill, NC USA.
[Penn, David] Australian Catholic Univ, Melbourne, Vic, Australia.
[Mueser, Kim T.] Boston Univ, Ctr Psychiat Rehabil, Boston, MA 02215 USA.
[Robinson, James A.] Nathan S Kline Inst Psychiat Res, Informat Sci Div, Orangeburg, NY USA.
[Rosenheck, Robert A.] Yale Univ, Sch Med, Dept Psychiat, West Haven, CT 06516 USA.
[Rosenheck, Robert A.] US Dept Vet Affairs, Mental Illness Res Educ & Clin Ctr, West Haven, CT USA.
RP Addington, J (reprint author), Univ Calgary, Dept Psychiat, Calgary, AB, Canada.
EM jmadding@ucalgary.ca
FU American Recovery and Reinvestment Act; National Institute of Mental
Health (NIMH) [HHSN271200900019C]; Asubio; Bristol-Myers Squibb;
Janssen; Otsuka; Shire; Genentech; Neurocrine; Roche; Sunovion;
Alkermes; Bristol-Myers Squibb Foundation; Janssen/JJ
FX This work has been funded in whole or in part with funds from the
American Recovery and Reinvestment Act and the National Institute of
Mental Health (NIMH) under contract HHSN271200900019C. The authors thank
RAISE-ETP participants, their families, and clinical and research staff
at our 34 sites. The contents are solely the responsibility of the
authors and do not necessarily represent the views of NIMH or the U.S.
Department of Health and Human Services.; Dr. Delbert G. Robinson has
been a consultant to or has received grants from Asubio, Bristol-Myers
Squibb, Janssen, Otsuka, and Shire. Dr. Schooler has received research
grants from, served on the advisory boards for, or served as a
consultant to Forum (formerly EnVivo), Genentech, Neurocrine, Otsuka,
Roche, and Sunovion. Ms. Marcy reports owning shares of Pfizer stock.
Dr. Brunette has received research grants from Alkermes and
Bristol-Myers Squibb Foundation. Dr. Correll has been a consultant or
advisor to or has received honoraria from Actelion, Alexza,
Bristol-Myers Squibb, Cephalon, Eli Lilly, Genentech, GersonLehrman
Group, IntraCellular Therapies, Janssen/J&J, Lundbeck, Medavante,
Medscape, Merck, Otsuka, Pfizer, ProPhase, Roche, Sunovion, Takeda,
Teva, and Vanda. He also received grant or material support in the form
of free medications from Bristol-Myers Squibb, Janssen/J&J, and Otsuka.
Dr. Kane has been a consultant or advisor to or has received honoraria
from Alkermes, Amgen, Bristol-Myers Squibb, Eli Lilly, Esai, Forrest
Labs, Genentech, Gerson Lehman Group, IntraCellular Therapies, Janssen,
Jazz, J&J, Lundbeck, MedAvante, Merck, Novartis, Otsuka, Pierre Fabre,
Proteus, Pfizer, Roche, Reviva, Sunovion, Takeda, Targacept, and Vanda,
and he is a shareholder of MedAvante. The other authors report no
financial relationships with commercial interests.
NR 15
TC 9
Z9 9
U1 5
U2 9
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 JUL
PY 2015
VL 66
IS 7
BP 753
EP 756
DI 10.1176/appi.ps.201400124
PG 4
WC Health Policy & Services; Public, Environmental & Occupational Health;
Psychiatry
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Psychiatry
GA DE5RO
UT WOS:000370689600016
PM 25588418
ER
PT J
AU Narayanasamy, G
Pyakuryal, AP
Pandit, S
Vincent, J
Lee, C
Mavroidis, P
Papanikolaou, N
Kudrimoti, M
Sio, TT
AF Narayanasamy, G.
Pyakuryal, A. P.
Pandit, S.
Vincent, J.
Lee, C.
Mavroidis, P.
Papanikolaou, N.
Kudrimoti, M.
Sio, T. T.
TI Radiobiological evaluation of intensity modulated radiation therapy
treatments of patients with head and neck cancer: A dual-institutional
study
SO JOURNAL OF MEDICAL PHYSICS
LA English
DT Article
DE Dysphagia; head and neck cancers; normal tissue complication
probability; radiobiology; xerostomia
ID NORMAL TISSUE; SALIVARY FUNCTION; GLAND FUNCTION; RADIOTHERAPY; VOLUME;
IRRADIATION; DYSPHAGIA; TOLERANCE; NTCP
AB In clinical practice, evaluation of clinical efficacy of treatment planning stems from the radiation oncologist's experience in accurately targeting tumors, while keeping minimal toxicity to various organs at risk (OAR) involved. A more objective, quantitative method may be raised by using radiobiological models. The purpose of this work is to evaluate the potential correlation of OAR-related toxicities to its radiobiologically estimated parameters in simultaneously integrated boost (SIB) intensity modulated radiation therapy (IMRT) plans of patients with head and neck tumors at two institutions. Lyman model for normal tissue complication probability (NTCP) and the Poisson model for tumor control probability (TCP) models were used in the Histogram Analysis in Radiation Therapy (HART) analysis. In this study, 33 patients with oropharyngeal primaries in the head and neck region were used to establish the correlation between NTCP values of (a) bilateral parotids with clinically observed rates of xerostomia, (b) esophagus with dysphagia, and (c) larynx with dysphagia. The results of the study indicated a strong correlation between the severity of xerostomia and dysphagia with Lyman NTCP of bilateral parotids and esophagus, respectively, but not with the larynx. In patients without complications, NTCP values of these organs were negligible. Using appropriate radiobiological models, the presence of a moderate to strong correlation between the severities of complications with NTCP of selected OARs suggested that the clinical outcome could be estimated prior to treatment.
C1 [Narayanasamy, G.; Vincent, J.; Mavroidis, P.; Papanikolaou, N.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiat Oncol, 7979 Wurzbach Rd, San Antonio, TX 78229 USA.
[Pyakuryal, A. P.; Lee, C.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Pandit, S.] BP Koirala Mem Canc Hosp, Dept Radiat Oncol, Bharatpur, Nepal.
[Kudrimoti, M.] Univ Kentucky, Dept Radiat Oncol, Lexington, KY USA.
[Sio, T. T.] Mayo Clin, Dept Radiat Oncol, Rochester, MN USA.
RP Narayanasamy, G (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Radiat Oncol, 7979 Wurzbach Rd, San Antonio, TX 78229 USA.
EM nganesh76@hotmail.com
NR 22
TC 0
Z9 0
U1 0
U2 0
PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD
PI MUMBAI
PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075,
INDIA
SN 0971-6203
EI 1998-3913
J9 J MED PHYS
JI J. Med. Phys.
PD JUL-SEP
PY 2015
VL 40
IS 3
BP 165
EP 169
DI 10.4103/0971-6203.165075
PG 5
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DE1LE
UT WOS:000370387700008
PM 26500403
ER
PT J
AU Grant, PM
Sheikh, V
DerSimonian, R
Rupert, A
Roby, G
Pau, A
Sneller, MC
Rico, SV
Brown, TT
Sereti, I
AF Grant, Philip M.
Sheikh, Virginia
DerSimonian, Rebecca
Rupert, Adam
Roby, Gregg
Pau, Alice
Sneller, Michael C.
Rico, Sheryl-vi
Brown, Todd T.
Sereti, Irini
TI Clinically Indicated Corticosteroids Do Not Affect Bone Turnover During
Immune Restoration of Severely Lymphopenic HIV-Infected Patients
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Article
ID ANTIRETROVIRAL THERAPY INITIATION; MINERAL DENSITY; ESTROGEN DEFICIENCY;
ABACAVIR-LAMIVUDINE; ELDERLY-MEN; OSTEOPOROSIS; FRACTURES; MARKERS;
COHORT; ADULTS
AB Lymphopenia, corticosteroids, antiretroviral therapy (ART), and inflammation negatively impact bone turnover and decrease bone mineral density, but their combined effect has not been evaluated. We examined the association between corticosteroids on bone turnover markers in severely lymphopenic HIV-infected patients initiating ART. Levels of osteocalcin (bone formation marker) and C-terminal telopeptide (CTX; bone resorption marker) were measured at baseline, weeks 4, 12, and 48 of ART in individuals with severe lymphopenia and opportunistic infection (OI) who received (n = 28) or did not receive corticosteroids (n = 30) during the first year of ART, and in a control group with CD4 > 200 (n = 15). Wilcoxon tests were used to compare median values of variables between groups. Correlations between plasma interleukin (IL)-6 and tumor necrosis factor (TNF) levels with bone turnover marker levels were performed using Spearman's coefficient. Individuals given corticosteroids received a median of 21 days at a 35 mg prednisone-equivalent daily dose. Individuals with severe lymphopenia had lower osteocalcin levels at baseline and week 4 and higher CTX levels at ART initiation vs. controls. Bone turnover markers did not differ in severely lymphopenic persons according to corticosteroid receipt. In those with severe lymphopenia, higher IL-6 was associated with higher CTX levels at ART initiation only. HIV-infected patients with severe lymphopenia and OI had lower levels of bone formation and higher levels of bone resorption than those initiating ART at higher CD4. Corticosteroid use, as prescribed during OI, was not associated with bone turnover. In contrast, higher markers of systemic inflammation prior to ART were associated with greater bone resorption.
C1 [Grant, Philip M.] Stanford Univ, Dept Med, Div Infect Dis, Stanford, CA 94305 USA.
[Sheikh, Virginia; DerSimonian, Rebecca; Roby, Gregg; Pau, Alice; Sneller, Michael C.; Rico, Sheryl-vi; Sereti, Irini] NIAID, NIH, Bethesda, MD 20892 USA.
[Rupert, Adam] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Brown, Todd T.] Johns Hopkins Univ, Dept Med, Div Endocrinol Diabet & Metab, Baltimore, MD USA.
RP Grant, PM (reprint author), Stanford Univ, Div Infect Dis & Geog Med, 300 Pasteur Dr,Room S-101, Stanford, CA 94305 USA.
EM pmgrant@stanford.edu
FU career development award from National Institute of Allergy and
Infectious Diseases (NIAID), National Institutes of Health (NIH) [K23
AI108358]; National Cancer Institute, NIH [HHS261200800001E]; Intramural
Research Program of NIAID, NIH
FX The authors would like to thank the study participants and the clinical
staff of the OP-8 HIV clinic at the NIH Clinical Center. This study was
supported in part by a career development award from the National
Institute of Allergy and Infectious Diseases (NIAID), National
Institutes of Health (NIH) (K23 AI108358), from the National Cancer
Institute, NIH (contract no. HHS261200800001E), and from the Intramural
Research Program of NIAID, NIH.
NR 29
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
EI 1931-8405
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD JUL
PY 2015
VL 31
IS 7
BP 739
EP 744
DI 10.1089/aid.2015.0028
PG 6
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA DD4IJ
UT WOS:000369885400012
PM 25919454
ER
PT J
AU Gartrell, K
Trinkoff, AM
Storr, CL
Wilson, ML
AF Gartrell, Kyungsook
Trinkoff, Alison M.
Storr, Carla L.
Wilson, Marisa L.
TI Electronic Personal Health Record Use Among Nurses in the Nursing
Informatics Community
SO CIN-COMPUTERS INFORMATICS NURSING
LA English
DT Article
DE Electronic health record; Health care provider; Nursing informatics;
Personal health record; Privacy
ID RANDOMIZED-TRIAL; MEDICAL RECORDS; PATIENTS ACCESS; EXPERIENCE;
MANAGEMENT; ATTITUDES; SYSTEM
AB An electronic personal health record is a patient-centric tool that enables patients to securely access, manage, and share their health information with healthcare providers. It is presumed the nursing informatics community would be early adopters of electronic personal health record, yet no studies have been identified that examine the personal adoption of electronic personal health record's for their own healthcare. For this study, we sampled nurse members of the American Medical Informatics Association and the Healthcare Information and Management Systems Society with 183 responding. Multiple logistic regression analysis was used to identify those factors associated with electronic personal health record use. Overall, 72% were electronic personal health record users. Users tended to be older (aged 950 years), be more highly educated (72% master's or doctoral degrees), and hold positions as clinical informatics specialists or chief nursing informatics officers. Those whose healthcare providers used electronic health records were significantly more likely to use electronic personal health records (odds ratio, 5.99; 95% confidence interval, 1.40-25.61). Electronic personal health record users were significantly less concerned about privacy of health information online than nonusers (odds ratio, 0.32; 95% confidence interval, 0.14-0.70) adjusted for ethnicity, race, and practice region. Informatics nurses, with their patient-centered view of technology, are in prime position to influence development of electronic personal health records. Our findings can inform policy efforts to encourage informatics and other professional nursing groups to become leaders and users of electronic personal health record; such use could help them endorse and engage patients to use electronic personal health records. Having champions with expertise in and enthusiasm for the new technology can promote the adoption of electronic personal health records among healthcare providers as well as their patients.
C1 [Gartrell, Kyungsook] NIH, Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20892 USA.
[Trinkoff, Alison M.; Storr, Carla L.] Univ Maryland, Sch Nursing, Baltimore, MD 21201 USA.
[Wilson, Marisa L.] Johns Hopkins Univ, Sch Nursing, Baltimore, MD USA.
RP Gartrell, K (reprint author), NIH, Bldg 10,Room 6-2551,10 Ctr Dr,MSC 1504, Bethesda, MD 20892 USA.
EM kyungsook.gartrell@nih.gov
FU American Nursing Informatics Association Scholarship Award; University
of Maryland School of Nursing
FX This work was supported by the American Nursing Informatics Association
Scholarship Award and by the University of Maryland School of Nursing.
NR 50
TC 0
Z9 0
U1 4
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1538-2931
EI 1538-9774
J9 CIN-COMPUT INFORM NU
JI CIN-Comput. Inform. Nurs.
PD JUL
PY 2015
VL 33
IS 7
BP 306
EP 314
DI 10.1097/CIN.0000000000000163
PG 9
WC Computer Science, Interdisciplinary Applications; Medical Informatics;
Nursing
SC Computer Science; Medical Informatics; Nursing
GA DD0SA
UT WOS:000369628500005
PM 26061563
ER
PT J
AU Mishra, RK
Yang, W
Roy, J
Anderson, AH
Bansal, N
Chen, J
DeFilippi, C
Delafontaine, P
Feldman, HI
Kallem, R
Kusek, JW
Lora, CM
Rosas, SE
Go, AS
Shlipak, MG
AF Mishra, Rakesh K.
Yang, Wei
Roy, Jason
Anderson, Amanda H.
Bansal, Nisha
Chen, Jing
DeFilippi, Christopher
Delafontaine, Patrice
Feldman, Harold I.
Kallem, Radhakrishna
Kusek, John W.
Lora, Claudia M.
Rosas, Sylvia E.
Go, Alan S.
Shlipak, Michael G.
CA CRIC Study Investigators
TI Kansas City Cardiomyopathy Questionnaire Score Is Associated With
Incident Heart Failure Hospitalization in Patients With Chronic Kidney
Disease Without Previously Diagnosed Heart Failure Chronic Renal
Insufficiency Cohort Study
SO CIRCULATION-HEART FAILURE
LA English
DT Article
DE heart failure; hospitalization; renal insufficiency, chronic
ID QUALITY-OF-LIFE; ACUTE MYOCARDIAL-INFARCTION; LEFT-VENTRICULAR
STRUCTURE; HEALTH-STATUS; EJECTION FRACTION; NATRIURETIC PEPTIDE;
DIASTOLIC FUNCTION; RISK; CKD; ECHOCARDIOGRAPHY
AB Background-Chronic kidney disease is a risk factor for heart failure (HF). Patients with chronic kidney disease without diagnosed HF have an increased burden of symptoms characteristic of HF. It is not known whether these symptoms are associated with occurrence of new onset HF.
Methods and Results-We studied the association of a modified Kansas City Cardiomyopathy Questionnaire with newly identified cases of hospitalized HF among 3093 participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study who did not report HF at baseline. The annually updated Kansas City Cardiomyopathy Questionnaire score was categorized into quartiles (Q1-4) with the lower scores representing the worse symptoms. Multivariable-adjusted repeated measure logistic regression models were adjusted for demographic characteristics, clinical risk factors for HF, N-terminal probrain natriuretic peptide level and left ventricular hypertrophy, left ventricular systolic and diastolic dysfunction. Over a mean (+/-SD) follow-up period of 4.3+/-1.6 years, there were 211 new cases of HF hospitalizations. The risk of HF hospitalization increased with increasing symptom quartiles; 2.62, 1.85, 1.14, and 0.74 events per 100 person-years, respectively. The median number of annual Kansas City Cardiomyopathy Questionnaire assessments per participant was 5 (interquartile range, 3-6). The annually updated Kansas City Cardiomyopathy Questionnaire score was independently associated with higher risk of incident HF hospitalization in multivariable-adjusted models (odds ratio, 3.30 [1.66-6.52]; P=0.001 for Q1 compared with Q4).
Conclusions-Symptoms characteristic of HF are common in patients with chronic kidney disease and are associated with higher short-term risk for new hospitalization for HF, independent of level of kidney function, and other known HF risk factors.
C1 [Mishra, Rakesh K.] Univ Calif San Francisco, Div Cardiol, San Francisco, CA 94143 USA.
[Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Yang, Wei; Roy, Jason; Anderson, Amanda H.; Feldman, Harold I.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Kallem, Radhakrishna] Univ Penn, Renal Electrolyte & Hypertens Div, Philadelphia, PA 19104 USA.
[Bansal, Nisha] Univ Washington, Div Nephrol, Seattle, WA 98195 USA.
[Chen, Jing] Tulane Univ, Dept Hypertens & Nephrol, New Orleans, LA 70118 USA.
[Delafontaine, Patrice] Tulane Univ, Dept Med, New Orleans, LA 70118 USA.
[DeFilippi, Christopher] Univ Maryland, Dept Med, College Pk, MD 20742 USA.
[Kusek, John W.] NIDDKD, NIH, Bethesda, MD USA.
[Lora, Claudia M.] Univ Illinois, Div Nephrol, Champaign, IL 61820 USA.
[Rosas, Sylvia E.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA.
[Rosas, Sylvia E.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA USA.
[Go, Alan S.] Kaiser Permanente Div Res, Oakland, CA USA.
[Mishra, Rakesh K.; Shlipak, Michael G.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA 94121 USA.
RP Shlipak, MG (reprint author), San Francisco VA Med Ctr, 4150 Clement St 111A1, San Francisco, CA 94121 USA.
EM michael.shlipak@ucsf.edu
OI Delafontaine, Patrice/0000-0003-3744-3617
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]; Johns Hopkins University
[UL1 TR-000424]; University of Maryland [GCRC M01 RR-16500]; Clinical
and Translational Science Collaborative of Cleveland from the NCATS
component of the National Institutes of Health [UL1TR000439]; NIH
roadmap for Medical Research; 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/NCRR [UCSF-CTSI UL1 RR-024131]; [R01 DK066488]
FX This project was supported by R01 DK066488 award (principal investigator
Dr Shlipak). Funding for the Chronic Renal Insufficiency Cohort (CRIC)
Study was obtained under a cooperative agreement from National Institute
of Diabetes and Digestive and Kidney Diseases (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)
UL1TR000003, Johns Hopkins University UL1 TR-000424, University of
Maryland GCRC M01 RR-16500, Clinical and Translational Science
Collaborative of Cleveland, UL1TR000439 from the NCATS component of the
National Institutes of Health and NIH roadmap for Medical Research,
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, and Kaiser Permanente
NIH/NCRR UCSF-CTSI UL1 RR-024131.
NR 28
TC 2
Z9 2
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1941-3289
EI 1941-3297
J9 CIRC-HEART FAIL
JI Circ.-Heart Fail.
PD JUL
PY 2015
VL 8
IS 4
BP 702
EP U31
DI 10.1161/CIRCHEARTFAILURE.115.002097
PG 12
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DD1XZ
UT WOS:000369717800004
PM 25985796
ER
PT J
AU Falk, DE
Castle, IJP
Ryan, M
Fertig, J
Litten, RZ
AF Falk, Daniel E.
Castle, I-Jen P.
Ryan, Megan
Fertig, Joanne
Litten, Raye Z.
TI Moderators of Varenicline Treatment Effects in a Double-Blind,
Placebo-Controlled Trial for Alcohol Dependence: An Exploratory Analysis
SO JOURNAL OF ADDICTION MEDICINE
LA English
DT Article
DE alcohol dependence; Chantix; moderator subgroup; randomized
placebo-controlled clinical trial; varenicline
ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; NICOTINIC
ACETYLCHOLINE-RECEPTORS; GENDER-DIFFERENCES; PARTIAL AGONIST; DSM-IV;
FAMILY-HISTORY; HEAVY-DRINKING; SERTRALINE; ALPHA-4-BETA-2; CONSUMPTION
AB Objectives: To explore whether varenicline (Chantix) showed more efficacy in treating certain subgroups of patients. In a recent multisite trial, varenicline was shown to be effective in reducing drinking in alcohol-dependent patients, both smokers and nonsmokers. Given the heterogeneity among alcohol-dependent patients, secondary analyses were conducted to determine whether certain subgroups responded more favorably than others to treatment with varenicline.
Methods: Data were drawn from a phase 2 randomized, double-blind, placebo-controlled multisite 13-week trial of varenicline in alcohol-dependent patients (Litten et al., 2013). Seventeen moderator variables were selected for exploratory testing on the basis of theoretical and scientific interest.
Results: Of the 17 moderator variables assessed, 4 were statistically significant, including cigarettes per day reduction, treatment drinking goal, years drinking regularly, and age of the patient. Two other variables-the type of adverse events experienced by patients and the severity of alcohol-related consequences-seemed to moderate the varenicline treatment effect at borderline statistical significance. Individuals who reduced the number of cigarettes per day experienced a significant effect from varenicline in reducing drinking, whereas those who did not change or who increased their number of cigarettes observed no beneficial effect. Reviewing the moderators related to severity, varenicline seemed to have greater efficacy than placebo among less severely dependent patients.
Conclusions: Varenicline seems to be more efficacious in certain subgroups, particularly in those who reduced their smoking and in the "less severe" patient. Additional studies are warranted to confirm the results of these exploratory analyses.
C1 [Falk, Daniel E.; Castle, I-Jen P.; Ryan, Megan; Fertig, Joanne; Litten, Raye Z.] NIAAA, Div Treatment & Recovery Res, 5635 Fishers Lane, Bethesda, MD 20892 USA.
[Castle, I-Jen P.] CSR Inc, Arlington, VA USA.
RP Falk, DE (reprint author), NIAAA, Div Treatment & Recovery Res, 5635 Fishers Lane, Bethesda, MD 20892 USA.
EM falkde@mail.nih.gov
FU National Institute on Alcohol Abuse and Alcoholism (NIAAA), National
Institutes of Health, Department of Health and Human Services, Bethesda,
MD; Medications Development Program [HHSN27200900005C]; NIAAA
[HHSN275201300016C]
FX Supported by the National Institute on Alcohol Abuse and Alcoholism
(NIAAA), National Institutes of Health, Department of Health and Human
Services, Bethesda, MD, and by the Medications Development Program
(Contract No. HHSN27200900005C), ClinicalTrials.gov NCT 01146613, and by
the NIAAA Alcohol Epidemiological Data System Contract (Contract No.
HHSN275201300016C) to CSR, Incorporated, Arlington, VA.
NR 40
TC 8
Z9 8
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1932-0620
EI 1935-3227
J9 J ADDICT MED
JI J. Addict. Med.
PD JUL-AUG
PY 2015
VL 9
IS 4
BP 296
EP 303
DI 10.1097/ADM.0000000000000133
PG 8
WC Substance Abuse
SC Substance Abuse
GA DD1VK
UT WOS:000369710500008
PM 26083958
ER
PT J
AU Olivier-Van Stichelen, S
Hanover, JA
AF Olivier-Van Stichelen, Stephanie
Hanover, John A.
TI You are what you eat: O-linked N-acetylglucosamine in disease,
development and epigenetics
SO CURRENT OPINION IN CLINICAL NUTRITION AND METABOLIC CARE
LA English
DT Review
DE development; epigenetics; intrauterine environment; metabolic syndrome;
O-linked N-acetylglucosamine
ID GLCNAC TRANSFERASE OGT; EMBRYONIC STEM-CELLS; GENE-EXPRESSION;
X-INACTIVATION; DIABETIC COMPLICATIONS; GLCNACYLATION; DIFFERENTIATION;
METABOLISM; CHROMATIN; STRESS
AB Purpose of review
The O-linked N-acetylglucosamine (O-GlcNAc) modification is both responsive to nutrient availability and capable of altering intracellular cellular signalling. We summarize data defining a role for O-GlcNAcylation in metabolic homeostasis and epigenetic regulation of development in the intrauterine environment.
Recent findings
O-GlcNAc transferase (OGT) catalyzes nutrient-driven O-GlcNAc addition and is subject to random X-inactivation. OGT plays key roles in growth factor signalling, stem cell biology, epigenetics and possibly imprinting. The O-GlcNAcase, which removes O-GlcNAc, is subject to tight regulation by higher order chromatin structure. O-GlcNAc cycling plays an important role in the intrauterine environment wherein OGT expression is an important biomarker of placental stress.
Summary
Regulation of O-GlcNAc cycling by X-inactivation, epigenetic regulation and nutrient-driven processes makes it an ideal candidate for a nutrient-dependent epigenetic regulator of human disease. In addition, O-GlcNAc cycling influences chromatin modifiers critical to the regulation and timing of normal development including the polycomb repression complex and the ten-eleven translocation proteins mediating DNA methyl cytosine demethylation. The pathway also impacts the hypothalamic-pituitary-adrenal axis critical to intrauterine programming influencing disease susceptibility in later life.
C1 [Olivier-Van Stichelen, Stephanie; Hanover, John A.] NIDDK, NIH, Bethesda, MD USA.
RP Hanover, JA (reprint author), NIDDK, NIH, Bethesda, MD USA.
EM jah@helix.nih.gov
FU Intramural Program of the National Institutes of Diabetes, Digestive and
Kidney Diseases (NIDDK), National Institutes of Health; Rotary
Foundation Ambassadorial Scholarship from the Rotary Foundation
FX This work was supported by the Intramural Program of the National
Institutes of Diabetes, Digestive and Kidney Diseases (NIDDK), National
Institutes of Health. Dr Stephanie Olivier-Van Stichelen received
support from the Rotary Foundation Ambassadorial Scholarship from the
Rotary Foundation.
NR 53
TC 3
Z9 3
U1 5
U2 12
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1363-1950
EI 1473-6519
J9 CURR OPIN CLIN NUTR
JI Curr. Opin. Clin. Nutr. Metab. Care
PD JUL
PY 2015
VL 18
IS 4
BP 339
EP 345
DI 10.1097/MCO.0000000000000188
PG 7
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA DD0QX
UT WOS:000369625600005
PM 26049631
ER
PT J
AU Gill, T
Asquith, M
Rosenbaum, JT
Colbert, RA
AF Gill, Tejpal
Asquith, Mark
Rosenbaum, James T.
Colbert, Robert A.
TI The intestinal microbiome in spondyloarthritis
SO CURRENT OPINION IN RHEUMATOLOGY
LA English
DT Review
DE ankylosing spondylitis; dysbiosis; HLA-B27; inflammatory bowel disease;
microbiome
ID HLA-B27 TRANSGENIC RATS; INFLAMMATORY-BOWEL-DISEASE; ENTHESITIS-RELATED
ARTHRITIS; REGULATORY T-CELLS; ANKYLOSING-SPONDYLITIS; GUT MICROBIOTA;
REACTIVE ARTHRITIS; SALMONELLA-TYPHIMURIUM; TRANSCRIPTION FACTOR;
PSORIATIC-ARTHRITIS
AB Purpose of review
Microbial dysbiosis in the gut is emerging as a common component in various inflammatory disorders including spondyloarthritis (SpA). The depth of this influence has begun to be realized with next-generation sequencing of the gut microbiome providing unbiased assessment of previously uncharted bacterial populations.
Recent findings
Decreased numbers of Firmicutes, a major phyla of gut commensals, especially the species Faecalibacterium prausnitzii and Clostridium leptum have been found in various inflammatory disorders including SpA and inflammatory bowel disease (IBD), and could be an important link between SpA and gut inflammation. Multiple studies in ankylosing spondylitis, psoriatic arthritis, juvenile SpA, and animal models of SpA are revealing common bacterial associations among these diseases as well as IBD.
Summary
We are beginning to appreciate the complex relationship between the gut microbiome and host immune regulation and dysregulation in health and disease. Potentially important differences have been revealed in SpA, but cause and effect relationships remain far from established. Many critical questions remain to be answered before we can apply new knowledge to improve therapeutics in SpA.
C1 [Gill, Tejpal; Colbert, Robert A.] NIAMSD, Pediat Translat Res Branch, NIH, Bldg 10-CRC,Room 1-5256,10 Ctr Dr, Bethesda, MD 20892 USA.
[Asquith, Mark; Rosenbaum, James T.] Oregon Hlth & Sci Univ, Legacy Devers Eye Inst, Div Arthrit & Rheumat Dis, Portland, OR 97201 USA.
RP Gill, T (reprint author), NIAMSD, Pediat Translat Res Branch, NIH, Bldg 10-CRC,Room 1-5256,10 Ctr Dr, Bethesda, MD 20892 USA.
EM tejpal.gill@nih.gov
FU Intramural Research Program Grant [Z01 AR041184]
FX The Intramural Research Program Grant Z01 AR041184 to Dr Robert A.
Colbert, NIAMS (NIH), supported this work.
NR 65
TC 18
Z9 18
U1 4
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1040-8711
EI 1531-6963
J9 CURR OPIN RHEUMATOL
JI Curr. Opin. Rheumatol.
PD JUL
PY 2015
VL 27
IS 4
BP 319
EP 325
DI 10.1097/BOR.0000000000000187
PG 7
WC Rheumatology
SC Rheumatology
GA DD0PO
UT WOS:000369622100001
PM 26002022
ER
PT J
AU Tan, S
Wang, RS
Ward, MM
AF Tan, Sovira
Wang, Runsheng
Ward, Michael M.
TI Syndesmophyte growth in ankylosing spondylitis
SO CURRENT OPINION IN RHEUMATOLOGY
LA English
DT Review
DE ankylosing spondylitis; computed tomography; MRI; syndesmophytes; tumor
necrosis factor-alpha inhibitors
ID SPONDYLOARTHRITIS INCEPTION COHORT; RADIOGRAPHIC SPINAL PROGRESSION;
AXIAL SPONDYLOARTHRITIS; STRUCTURAL DAMAGE; INFLAMMATORY LESIONS;
DISEASE-ACTIVITY; BONE-FORMATION; PREDICTORS; DICKKOPF-1; CT
AB Purpose of review
Syndesmophytes are characteristic components of the spine disorder of ankylosing spondylitis. Understanding their growth may reveal insights to pathogenesis and potential treatment. We review recent studies on rates of development of syndesmophytes, patient characteristics associated with more rapid syndesmophyte growth, local vertebral abnormalities that precede syndesmophytes, systemic biomarkers of syndesmophytes, and studies of medications.
Recent findings
New syndesmophytes develop in one-third of patients over 2 years. Consistent clinical predictors are male sex, elevated serum C-reactive protein levels, and preexisting syndesmophytes. Concomitant vertebral inflammation and fat dysplasia on MRI predict future syndesmophytes at the same vertebral location, but most syndesmophytes do not have recognized antecedents. Associations with serum levels of Wingless pathway proteins are inconsistent, as are the results of observational studies of tumor necrosis factor-alpha inhibitors.
Summary
Although there is better understanding of the frequency of syndesmophyte development, the pathogenesis of syndesmophytes remains unclear.
C1 [Tan, Sovira; Wang, Runsheng; Ward, Michael M.] NIAMSD, Intramural Res Program, NIH, Bldg 10 CRC,Room 4-1339,10 Ctr Dr, Bethesda, MD 20892 USA.
RP Ward, MM (reprint author), NIAMSD, Intramural Res Program, NIH, Bldg 10 CRC,Room 4-1339,10 Ctr Dr, Bethesda, MD 20892 USA.
EM wardm1@mail.nih.gov
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases,
National Institutes of Health
FX This work was supported by the Intramural Research Program, National
Institute of Arthritis and Musculoskeletal and Skin Diseases, National
Institutes of Health.
NR 30
TC 2
Z9 2
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1040-8711
EI 1531-6963
J9 CURR OPIN RHEUMATOL
JI Curr. Opin. Rheumatol.
PD JUL
PY 2015
VL 27
IS 4
BP 326
EP 332
DI 10.1097/BOR.0000000000000179
PG 7
WC Rheumatology
SC Rheumatology
GA DD0PO
UT WOS:000369622100002
PM 26002023
ER
PT J
AU Ombrello, MJ
Kastner, DL
Remmers, EF
AF Ombrello, Michael J.
Kastner, Daniel L.
Remmers, Elaine F.
TI Endoplasmic reticulum-associated amino-peptidase 1 and rheumatic
disease: genetics
SO CURRENT OPINION IN RHEUMATOLOGY
LA English
DT Review
DE antigen processing; epistasis; major histocompatibility complex
ID PSORIASIS SUSCEPTIBILITY LOCI; GENOME-WIDE ASSOCIATION;
ANKYLOSING-SPONDYLITIS; CHINESE POPULATION; ERAP1; HLA-B27;
IDENTIFICATION; POLYMORPHISM; INDIVIDUALS; HAPLOTYPES
AB Purpose of review
This article will review the genetic evidence implicating ERAP1, which encodes the endoplasmic reticulum-associated amino-peptidase 1, in susceptibility to rheumatic disease.
Recent findings
Genetic variants and haplotypes of ERAP1 are associated with AS, psoriasis, and Behc, et's disease in people of varying ancestries. In each of these diseases, disease-associated variants of ERAP1 have been shown to interact with disease-associated class I human leukocyte antigen alleles to influence disease risk. Functionally, disease-associated missense variants of ERAP1 concertedly alter ERAP1 enzymatic function, both quantitatively and qualitatively, whereas other disease-associated variants influence ERAP1 expression. Therefore, ERAP1 haplotypes (or allotypes) should be examined as functional units. Biologically, this amounts to an examination of the gene regulation and function of the protein encoded by each allotype. Genetically, the relationship between disease risk and ERAP1 allotypes should be examined to determine whether allotypes or individual variants produce the most parsimonious risk models.
Summary
Future investigations of ERAP1 should focus on comprehensively characterizing naturally occurring ERAP1 allotypes, examining the enzymatic function and gene expression of each allotype, and identifying specific allotypes that influence disease susceptibility.
C1 [Ombrello, Michael J.] NIAMSD, Translat Genet & Genom Unit, NIH, Bethesda, MD 20892 USA.
[Kastner, Daniel L.; Remmers, Elaine F.] NHGRI, Inflammatory Dis Sect, NIH, Bethesda, MD 20892 USA.
RP Ombrello, MJ (reprint author), 10 Ctr Dr,MSC 1560,Bldg 10,Room 10C101A, Bethesda, MD 20892 USA.
EM ombrellomj@mail.nih.gov
FU Intramural Research Programs of the National Institute of Arthritis and
Musculoskeletal and Skin Diseases [Z01 AR041198]; National Human Genome
Research Institute, National Institutes of Health, Bethesda, U.S.A. [Z01
HG200374]
FX This study was supported by the Intramural Research Programs of the
National Institute of Arthritis and Musculoskeletal and Skin Diseases
(Z01 AR041198) and the National Human Genome Research Institute (Z01
HG200374), National Institutes of Health, Bethesda, U.S.A.
NR 28
TC 7
Z9 7
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1040-8711
EI 1531-6963
J9 CURR OPIN RHEUMATOL
JI Curr. Opin. Rheumatol.
PD JUL
PY 2015
VL 27
IS 4
BP 349
EP 356
DI 10.1097/BOR.0000000000000189
PG 8
WC Rheumatology
SC Rheumatology
GA DD0PO
UT WOS:000369622100005
PM 26002026
ER
PT J
AU Tran, TM
Colbert, RA
AF Tran, Tri M.
Colbert, Robert A.
TI Endoplasmic reticulum aminopeptidase 1 and rheumatic disease: functional
variation
SO CURRENT OPINION IN RHEUMATOLOGY
LA English
DT Review
DE ankylosing spondylitis; endoplasmic reticulum aminopeptidase 1; human
leukocyte antigen B27; rheumatic disease
ID GENOME-WIDE ASSOCIATION; CLASS-I MOLECULES; ANKYLOSING-SPONDYLITIS;
SUSCEPTIBILITY LOCI; CROSS-PRESENTATION; ER AMINOPEPTIDASE; ERAP1;
PEPTIDES; HLA-B27; IMMUNODOMINANCE
AB Purpose of review
To review the recent developments in our understanding of endoplasmic reticulum (ER) aminopeptidase 1 (ERAP1) function in relation to its role in major histocompatibility complex (MHC) class I peptide presentation and human leukocyte antigen (HLA) class I-associated diseases.
Recent findings
ERAP1 polymorphisms exhibiting loss-of-function have been associated with protection from AS. The aminopeptidase function of ERAP1 optimizes peptides for binding and presentation by MHC class I. Most of the studies have revealed reduced MHC class I expression in situations of reduced ERAP1 function. Under these circumstances, the presented peptides are often N-terminally extended, and cell surface complexes are unstable and fall apart more readily. In contrast, peptides presented by HLA-B*27 : 05 when ERAP1 is silenced are frequently extended on the C-terminus. Recent work has emphasized on the importance of assessing the function of allotypes encoded by ERAP1 haplotypes, rather than effects of single amino acid substitutions. The allotypes found in a series of AS patients were poorer at restoring HLAB-27 expression than allotypes found in unaffected controls, which may seem contrary to the genetic data linking loss-of-function to protection.
Summary
More work is needed to understand how ERAP1 variants associated with risk and protection influence the quality and quantity of peptides available for binding to HLA class I molecules in the ER. Moreover, we need to determine allele-specific effects of ERAP1 variants in the context of HLA-B*51 and HLA-Cw*6, which are associated with Behc, et's disease and psoriasis, respectively.
C1 [Tran, Tri M.; Colbert, Robert A.] NIAMSD, Pediat Translat Res Branch, NIH, Bethesda, MD 20892 USA.
RP Tran, TM (reprint author), Bldg 10-CRC,Room 1-5256,10 Ctr Dr, Bethesda, MD 20814 USA.
EM tri.tran@nih.gov
FU Intramural Research Program of the National Institute of Arthritis
Musculoskeletal and Skin Diseases of the National Institutes of Health,
Bethesda, MD, USA [Z01 AR041184]
FX This work was supported by the Intramural Research Program of the
National Institute of Arthritis Musculoskeletal and Skin Diseases (Z01
AR041184) of the National Institutes of Health, Bethesda, MD, USA.
NR 35
TC 6
Z9 6
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1040-8711
EI 1531-6963
J9 CURR OPIN RHEUMATOL
JI Curr. Opin. Rheumatol.
PD JUL
PY 2015
VL 27
IS 4
BP 357
EP 363
DI 10.1097/BOR.0000000000000188
PG 7
WC Rheumatology
SC Rheumatology
GA DD0PO
UT WOS:000369622100006
PM 26002027
ER
PT J
AU Romero, R
Hernandez-Andrade, E
AF Romero, Roberto
Hernandez-Andrade, Edgar
TI Doppler of the middle cerebral artery for the assessment of fetal
well-being
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Editorial Material
ID VELOCITY WAVE-FORMS; CEREBROPLACENTAL RATIO
C1 Natl Inst Hlth, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prog Perinatal Res & Obstet, Perinatol Res Branch, Detroit, MI USA.
Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI USA.
Detroit Med Ctr, Detroit, MI USA.
RP Romero, R (reprint author), Natl Inst Hlth, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prog Perinatal Res & Obstet, Perinatol Res Branch, Detroit, MI USA.
NR 9
TC 2
Z9 2
U1 1
U2 2
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 JUL
PY 2015
VL 213
IS 1
BP 1
EP 1
DI 10.1016/j.ajog.2015.05.064
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA CL3FQ
UT WOS:000356836200050
PM 26113225
ER
PT J
AU Detweiler, MB
Self, JA
Lane, S
Spencer, L
Lutgens, B
Kim, DY
Halling, MH
Rudder, TF
Lehmann, L
AF Detweiler, Mark B.
Self, Jennifer A.
Lane, Sandra
Spencer, Luise
Lutgens, Brian
Kim, Dong-Yun
Halling, Mary H.
Rudder, Tammie F.
Lehmann, Lauren
TI Horticultural Therapy: A Pilot Study on Modulating Cortisol Levels and
Indices of Substance Craving, Posttraumatic Stress Disorder, Depression,
and Quality of Life in Veterans
SO ALTERNATIVE THERAPIES IN HEALTH AND MEDICINE
LA English
DT Article
ID WANDER GARDEN; RESTORATION; SURGERY; PLACES
AB Context Horticultural therapy (HT) is a subgroup of occupational therapy (OT). Both HT and OT have been successful as adjunctive treatment modalities in substance abuse treatment. Studies have indicated that gardening promotes neuroendocrine and affective restoration from stress.
Objectives The study intended to assess the effect of HT versus nonhorticultural OT on cortisol levels, depression, symptoms of posttraumatic stress disorder (PTSD), alcohol cravings, and quality of life.
Methods The research team designed a randomized pilot study.
Setting The study was open for participation from July 2012-October 2012. It took place during multiple occurrences of a 28-d treatment programs for substance use disorder at a Veterans Affairs medical center.
Participants Participants were 49 veterans, averaging 46.4 y old (SD = 11.9); the dropout rate was 37%. Intervention " Participants were randomly assigned to the HT or the OT group. They attended supervised HT and OT groups 5 h/d for 3 wk.
Outcome Measures Pre- and posttreatment, participants completed the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF), the Alcohol Craving Questionnaire (ACQ-NOW), the Posttraumatic Stress Disorder Checklist Civilian Version (PCLC), and the Center for Epidemiologic Studies Depression Scale (CES-D). Salivary cortisol samples were taken at wk 1, 2, and 3.
Results A repeated measures analysis of variance (ANOVA) (F-220 = 0.878) revealed that the HT performed was associated with a 12% reduction in salivary cortisol levels from wk 1 to wk 3, but the difference was not statistically significant (P =.43). Separate 1-way analyses of covariance (ANCOVAs) revealed no statistically significant differences in the self-administered tests, although both the Q-LES-Q-SF and CES-D showed a trend toward improving quality of life and depressive symptoms in the HT group compared with the OT group. Additional analysis of the nonbiologic tests suggests that most participants in the HT and OT had some benefit from the programmed activities.
Conclusions The trends suggest that HT may modulate stress in veterans, as evidenced by decreased cortisol levels and depressive symptoms, and may improve quality of life more than the programs in which the OT group participated. Further investigation with larger samples, including a nontreatment control group, is needed to determine whether the observed trends are treatment effects or due to abstinence.
C1 [Detweiler, Mark B.] SVAMC, Salem, VA USA.
[Detweiler, Mark B.; Lehmann, Lauren] Virginia Tech, Caril Sch Med, Dept Psychiat & Behav Med, Roanoke, VA USA.
[Detweiler, Mark B.; Lutgens, Brian; Kim, Dong-Yun; Halling, Mary H.] SVAMC, Geriatr Res Grp, Salem, VA USA.
[Self, Jennifer A.] SVAMC, Dept Psychol, Salem, VA USA.
[Lane, Sandra; Spencer, Luise; Lehmann, Lauren] SVAMC, Salem, VA USA.
[Kim, Dong-Yun] NHLBI, Off Biostat Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Rudder, Tammie F.] SVAMC, Rehabil & Treatment Program, Salem, VA USA.
[Lehmann, Lauren] SVAMC, Subst Abuse Residential Rehabil & Treatment Progr, Salem, VA USA.
RP Detweiler, MB (reprint author), SVAMC, Salem, VA USA.
EM Mark.Detweiler1@va.gov
NR 33
TC 0
Z9 1
U1 10
U2 25
PU INNOVISION COMMUNICATIONS
PI ALISO VIEJO
PA 101 COLUMBIA, ALISO VIEJO, CA 92656 USA
SN 1078-6791
J9 ALTERN THER HEALTH M
JI Altern. Ther. Health Med.
PD JUL-AUG
PY 2015
VL 21
IS 4
BP 36
EP 41
PG 6
WC Integrative & Complementary Medicine
SC Integrative & Complementary Medicine
GA DB8EH
UT WOS:000368749300006
PM 26030115
ER
PT J
AU Aivaz, O
Berkman, S
Middelton, L
Linehan, WM
DiGiovanna, JJ
Cowen, EW
AF Aivaz, Ohara
Berkman, Suzanne
Middelton, Lindsay
Linehan, W. Marston
DiGiovanna, John J.
Cowen, Edward W.
TI Comedonal and Cystic Fibrofolliculomas in Birt-Hogg-Dube Syndrome
SO JAMA DERMATOLOGY
LA English
DT Article
ID MULTIPLE FIBROFOLLICULOMAS; HAMARTOMA; MUTATIONS; DISEASE; TUMORS
AB IMPORTANCE The differential diagnosis of extensive open comedones includes inherited genetic syndromes and several acquired conditions. Birt-Hogg-Dube syndrome (BHD) is not typically included in the differential diagnosis of syndromes with comedonal lesions. Given the potentially life-threatening systemic complications associated with BHD, early recognition and diagnosis of the condition is important.
OBSERVATIONS We describe comedonal or cystic fibrofolliculomas in 4 patients with BHD. Cutaneous lesions were identified on the face, neck, chest, and abdomen.
CONCLUSIONS AND RELEVANCE Comedonal or cystic fibrofolliculomas are a variant of fibrofolliculomas that have not previously been well characterized in patients with BHD and represent a novel diagnostic clue to its early detection and diagnosis. Expanding the phenotypic features of BHD facilitates earlier diagnosis of the syndrome, which allows for early surveillance of renal cancer in affected patients as well as disease screening in their relatives.
C1 [Aivaz, Ohara] Georgetown Univ Hosp, Washington Hosp Ctr, Dept Dermatol, Washington, DC 20007 USA.
[Berkman, Suzanne] Suzanne L Berkman MD Inc, Beverly Hills, CA USA.
[Middelton, Lindsay; Linehan, W. Marston] NCI, Urol Surg & Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
[DiGiovanna, John J.; Cowen, Edward W.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Cowen, EW (reprint author), NCI, Dermatol Branch, Ctr Canc Res, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM cowene@mail.nih.gov
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health
FX This study was supported by the Center for Cancer Research, National
Cancer Institute, National Institutes of Health.
NR 15
TC 0
Z9 0
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6068
EI 2168-6084
J9 JAMA DERMATOL
JI JAMA Dermatol.
PD JUL
PY 2015
VL 151
IS 7
BP 770
EP 774
DI 10.1001/jamadermatol.2015.0215
PG 5
WC Dermatology
SC Dermatology
GA DA7OE
UT WOS:000367992800017
PM 25970555
ER
PT J
AU Pine, DS
Leibenluft, E
AF Pine, Daniel S.
Leibenluft, Ellen
TI Biomarkers With a Mechanistic Focus
SO JAMA PSYCHIATRY
LA English
DT Editorial Material
ID PSYCHIATRY
C1 [Pine, Daniel S.; Leibenluft, Ellen] NIMH, Emot & Dev Branch, Intramural Res Program, Bethesda, MD 20892 USA.
RP Pine, DS (reprint author), 15K North Dr,MSC 2670, Bethesda, MD 20892 USA.
EM daniel.pine@nih.gov
NR 8
TC 10
Z9 10
U1 1
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-622X
EI 2168-6238
J9 JAMA PSYCHIAT
JI JAMA Psychiatry
PD JUL
PY 2015
VL 72
IS 7
BP 633
EP 634
DI 10.1001/jamapsychiatry.2015.0498
PG 2
WC Psychiatry
SC Psychiatry
GA DA1PQ
UT WOS:000367568100002
PM 25992716
ER
PT J
AU de Moor, MHM
van den Berg, SM
Verweij, KJH
Krueger, RF
Luciano, M
Vasquez, AA
Matteson, LK
Derringer, J
Esko, T
Amin, N
Gordon, SD
Hansell, NK
Hart, AB
Seppala, I
Huffman, JE
Konte, B
Lahti, J
Lee, M
Miller, M
Nutile, T
Tanaka, T
Teumer, A
Viktorin, A
Wedenoja, J
Abecasis, GR
Adkins, DE
Agrawal, A
Allik, J
Appel, K
Bigdeli, TB
Busonero, F
Campbell, H
Costa, PT
Smith, GD
Davies, G
de Wit, H
Ding, J
Engelhardt, BE
Eriksson, JG
Fedko, IO
Ferrucci, L
Franke, B
Giegling, I
Grucza, R
Hartmann, AM
Heath, AC
Heinonen, K
Henders, AK
Homuth, G
Hottenga, JJ
Iacono, WG
Janzing, J
Jokela, M
Karlsson, R
Kemp, JP
Kirkpatrick, MG
Latvala, A
Lehtimaki, T
Liewald, DC
Madden, PAF
Magri, C
Magnusson, PKE
Marten, J
Maschio, A
Medland, SE
Mihailov, E
Milaneschi, Y
Montgomery, GW
Nauck, M
Ouwens, KG
Palotie, A
Pettersson, E
Polasek, O
Qian, Y
Pulkki-Raback, L
Raitakari, OT
Realo, A
Rose, RJ
Ruggiero, D
Schmidt, CO
Slutske, WS
Sorice, R
Starr, JM
St Pourcain, B
Sutin, AR
Timpson, NJ
Trochet, H
Vermeulen, S
Vuoksimaa, E
Widen, E
Wouda, J
Wright, MJ
Zgaga, L
Porteous, D
Minelli, A
Palmer, AA
Rujescu, D
Ciullo, M
Hayward, C
Rudan, I
Metspalu, A
Kaprio, J
Deary, IJ
Raikkonen, K
Wilson, JF
Keltikangas-Jarvinen, L
Bierut, LJ
Hettema, JM
Grabe, HJ
van Duijn, CM
Evans, DM
Schlessinger, D
Pedersen, NL
Terracciano, A
McGue, M
Penninx, BJH
Martin, NG
Boomsma, DI
AF de Moor, Marleen H. M.
van den Berg, Stephanie M.
Verweij, Karin J. H.
Krueger, Robert F.
Luciano, Michelle
Vasquez, Alejandro Arias
Matteson, Lindsay K.
Derringer, Jaime
Esko, Tonu
Amin, Najaf
Gordon, Scott D.
Hansell, Narelle K.
Hart, Amy B.
Seppala, Ilkka
Huffman, Jennifer E.
Konte, Bettina
Lahti, Jari
Lee, Minyoung
Miller, Mike
Nutile, Teresa
Tanaka, Toshiko
Teumer, Alexander
Viktorin, Alexander
Wedenoja, Juho
Abecasis, Goncalo R.
Adkins, Daniel E.
Agrawal, Arpana
Allik, Jueri
Appel, Katja
Bigdeli, Timothy B.
Busonero, Fabio
Campbell, Harry
Costa, Paul T.
Smith, George Davey
Davies, Gail
de Wit, Harriet
Ding, Jun
Engelhardt, Barbara E.
Eriksson, Johan G.
Fedko, Iryna O.
Ferrucci, Luigi
Franke, Barbara
Giegling, Ina
Grucza, Richard
Hartmann, Annette M.
Heath, Andrew C.
Heinonen, Kati
Henders, Anjali K.
Homuth, Georg
Hottenga, Jouke-Jan
Iacono, William G.
Janzing, Joost
Jokela, Markus
Karlsson, Robert
Kemp, John P.
Kirkpatrick, Matthew G.
Latvala, Antti
Lehtimaki, Terho
Liewald, David C.
Madden, Pamela A. F.
Magri, Chiara
Magnusson, Patrik K. E.
Marten, Jonathan
Maschio, Andrea
Medland, Sarah E.
Mihailov, Evelin
Milaneschi, Yuri
Montgomery, Grant W.
Nauck, Matthias
Ouwens, Klaasjan G.
Palotie, Aarno
Pettersson, Erik
Polasek, Ozren
Qian, Yong
Pulkki-Raback, Laura
Raitakari, Olli T.
Realo, Anu
Rose, Richard J.
Ruggiero, Daniela
Schmidt, Carsten O.
Slutske, Wendy S.
Sorice, Rossella
Starr, John M.
St Pourcain, Beate
Sutin, Angelina R.
Timpson, Nicholas J.
Trochet, Holly
Vermeulen, Sita
Vuoksimaa, Eero
Widen, Elisabeth
Wouda, Jasper
Wright, Margaret J.
Zgaga, Lina
Porteous, David
Minelli, Alessandra
Palmer, Abraham A.
Rujescu, Dan
Ciullo, Marina
Hayward, Caroline
Rudan, Igor
Metspalu, Andres
Kaprio, Jaakko
Deary, Ian J.
Raikkonen, Katri
Wilson, James F.
Keltikangas-Jarvinen, Liisa
Bierut, Laura J.
Hettema, John M.
Grabe, Hans J.
van Duijn, Cornelia M.
Evans, David M.
Schlessinger, David
Pedersen, Nancy L.
Terracciano, Antonio
McGue, Matt
Penninx, BrendaW. J. H.
Martin, Nicholas G.
Boomsma, Dorret I.
CA Genetics Personality Consortium
TI Meta-analysis of Genome-wide Association Studies for Neuroticism, and
the Polygenic Association With Major Depressive Disorder
SO JAMA PSYCHIATRY
LA English
DT Article
ID POPULATION-BASED TWIN; COMMON SNPS EXPLAIN; MULTIDIMENSIONAL PERSONALITY
QUESTIONNAIRE; BIPOLAR AFFECTIVE-DISORDER; ITEM RESPONSE THEORY;
5-FACTOR MODEL; GENETIC-VARIATION; PSYCHOBIOLOGICAL MODEL; LARGE
PROPORTION; HUMAN HEIGHT
AB IMPORTANCE Neuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63 000 participants (including MDD cases).
OBJECTIVES To identify genetic variants associated with neuroticism by performing a meta-analysis of genome-wide association results based on 1000 Genomes imputation; to evaluate whether common genetic variants as assessed by single-nucleotide polymorphisms (SNPs) explain variation in neuroticism by estimating SNP-based heritability; and to examine whether SNPs that predict neuroticism also predict MDD.
DESIGN, SETTING, AND PARTICIPANTS Genome-wide association meta-analysis of 30 cohorts with genome-wide genotype, personality, and MDD data from the Genetics of Personality Consortium. The study included 63 661 participants from 29 discovery cohorts and 9786 participants from a replication cohort. Participants came from Europe, the United States, or Australia. Analyses were conducted between 2012 and 2014.
MAIN OUTCOMES AND MEASURES Neuroticism scores harmonized across all 29 discovery cohorts by item response theory analysis, and clinical MDD case-control status in 2 of the cohorts.
RESULTS A genome-wide significant SNP was found on 3p14 in MAGI1 (rs35855737; P = 9.26 x 10(-9) in the discovery meta-analysis). This association was not replicated (P = .32), but the SNP was still genome-wide significant in the meta-analysis of all 30 cohorts (P = 2.38 x 10(-8)). Common genetic variants explain 15% of the variance in neuroticism. Polygenic scores based on the meta-analysis of neuroticism in 27 cohorts significantly predicted neuroticism (1.09 x 10(-12) < P < .05) and MDD (4.02 x 10(-9) < P < .05) in the 2 other cohorts.
CONCLUSIONS AND RELEVANCE This study identifies a novel locus for neuroticism. The variant is located in a known gene that has been associated with bipolar disorder and schizophrenia in previous studies. In addition, the study shows that neuroticism is influenced by many genetic variants of small effect that are either common or tagged by common variants. These genetic variants also influence MDD. Future studies should confirm the role of the MAGI1 locus for neuroticism and further investigate the association of MAGI1 and the polygenic association to a range of other psychiatric disorders that are phenotypically correlated with neuroticism.
C1 [de Moor, Marleen H. M.] Vrije Univ Amsterdam, Dept Clin Child & Family Studies, NL-1081 BT Amsterdam, Netherlands.
[de Moor, Marleen H. M.] Vrije Univ Amsterdam, Dept Methods, NL-1081 BT Amsterdam, Netherlands.
[de Moor, Marleen H. M.; Fedko, Iryna O.; Hottenga, Jouke-Jan; Ouwens, Klaasjan G.; Wouda, Jasper; Boomsma, Dorret I.] Vrije Univ Amsterdam, Dept Biol Psychol, NL-1081 BT Amsterdam, Netherlands.
[van den Berg, Stephanie M.; Wouda, Jasper] Univ Twente, Dept Res Methodol Measurement & Data Anal, NL-7500 AE Enschede, Netherlands.
[Verweij, Karin J. H.] Vrije Univ Amsterdam, EMGO Inst Hlth & Care Res, Dept Dev Psychol, NL-1081 BT Amsterdam, Netherlands.
[Verweij, Karin J. H.; Gordon, Scott D.; Hansell, Narelle K.; Henders, Anjali K.; Medland, Sarah E.; Montgomery, Grant W.; Wright, Margaret J.; Martin, Nicholas G.] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia.
[Matteson, Lindsay K.; Miller, Mike; Iacono, William G.; McGue, Matt] Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA.
[Luciano, Michelle; Davies, Gail; Liewald, David C.; Starr, John M.; Deary, Ian J.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.
[Luciano, Michelle; Davies, Gail; Liewald, David C.; Deary, Ian J.] Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland.
[Vasquez, Alejandro Arias] Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neurosci, NL-6525 ED Nijmegen, Netherlands.
[Vasquez, Alejandro Arias; Franke, Barbara] Radboud Univ Nijmegen, Donders Inst Cognit Neurosci, NL-6525 ED Nijmegen, Netherlands.
[Vasquez, Alejandro Arias; Franke, Barbara; Janzing, Joost] Radboud Univ Nijmegen, Med Ctr, Dept Psychiat, NL-6525 ED Nijmegen, Netherlands.
[Vasquez, Alejandro Arias; Franke, Barbara; Vermeulen, Sita] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands.
[Derringer, Jaime] Univ Illinois, Dept Psychol, Champaign, IL 61820 USA.
[Esko, Tonu; Mihailov, Evelin; Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.
[Amin, Najaf; van Duijn, Cornelia M.] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
[Hart, Amy B.; Palmer, Abraham A.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
[Seppala, Ilkka; Lehtimaki, Terho] Univ Tampere, Fimlab Labs, FIN-33101 Tampere, Finland.
[Seppala, Ilkka; Lehtimaki, Terho] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland.
[Huffman, Jennifer E.; Marten, Jonathan; Trochet, Holly; Hayward, Caroline] Univ Edinburgh, Western Gen Hosp, MRC Inst Genet & Mol Med, Med Res Council Human Genet, Edinburgh, Midlothian, Scotland.
[Konte, Bettina; Giegling, Ina; Hartmann, Annette M.; Rujescu, Dan] Univ Halle Wittenberg, Dept Psychiat, D-06108 Halle, Germany.
[Lahti, Jari; Eriksson, Johan G.; Terracciano, Antonio] Folkhalsan Res Ctr, Helsinki, Finland.
[Lahti, Jari; Heinonen, Kati; Jokela, Markus; Pulkki-Raback, Laura; Raikkonen, Katri; Keltikangas-Jarvinen, Liisa] Univ Helsinki, Inst Behav Sci, Helsinki, Finland.
[Lee, Minyoung; Bigdeli, Timothy B.; Hettema, John M.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Dept Psychiat, Richmond, VA 23284 USA.
[Nutile, Teresa; Ruggiero, Daniela; Sorice, Rossella; Ciullo, Marina; Pedersen, Nancy L.] Natl Res Council Italy, Inst Genet & Biophys A Buzzati Traverso, Naples, Italy.
[Tanaka, Toshiko; Ding, Jun; Ferrucci, Luigi; Qian, Yong; Sutin, Angelina R.; Schlessinger, David] Natl Inst Aging, Natl Inst Hlth, Baltimore, MD USA.
[Teumer, Alexander; Schmidt, Carsten O.] Univ Med Greifswald, Inst Community Med, Greifswald, Germany.
[Viktorin, Alexander; Karlsson, Robert; Magnusson, Patrik K. E.; Pettersson, Erik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Wedenoja, Juho; Latvala, Antti; Vuoksimaa, Eero; Kaprio, Jaakko] Univ Helsinki, Dept Publ Hlth, Helsinki, Finland.
[Abecasis, Goncalo R.] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Adkins, Daniel E.] Virginia Commonwealth Univ, Dept Pharmacotherapy & Outcomes Sci, Richmond, VA 23284 USA.
[Agrawal, Arpana; Grucza, Richard; Heath, Andrew C.; Madden, Pamela A. F.; Bierut, Laura J.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
[Allik, Jueri; Realo, Anu] Univ Tartu, Dept Psychol, EE-50090 Tartu, Estonia.
[Allik, Jueri; Metspalu, Andres] Estonian Acad Sci, EE-200103 Tallinn, Estonia.
[Appel, Katja; Grabe, Hans J.] Univ Med Greifswald, Dept Psychiat & Psychotherapy, Greifswald, Germany.
[Busonero, Fabio; Maschio, Andrea] Natl Res Council Italy, Ist Ric Genet & Biomed, Monserrato, Italy.
[Campbell, Harry; Zgaga, Lina; Rudan, Igor; Wilson, James F.] Univ Edinburgh, Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.
[Costa, Paul T.] Duke Univ, Sch Med, Behav Med Res Ctr, Durham, NC USA.
[Smith, George Davey; Kemp, John P.; St Pourcain, Beate; Timpson, Nicholas J.; Evans, David M.] Univ Bristol, Sch Social & Community Med, Med Res Council Integrat Epidemiol Unit, Bristol BS8 1TH, Avon, England.
[de Wit, Harriet; Kirkpatrick, Matthew G.; Palmer, Abraham A.] Univ Chicago, Dept Psychiat & Behav Neurosci, Chicago, IL 60637 USA.
[Engelhardt, Barbara E.] Princeton Univ, Dept Comp Sci, Princeton, NJ 08544 USA.
[Eriksson, Johan G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland.
[Eriksson, Johan G.] Helsinki Univ Hosp, Helsinki, Finland.
[Eriksson, Johan G.] Vasa Cent Hosp, Vaasa, Finland.
[Eriksson, Johan G.; Latvala, Antti; Kaprio, Jaakko] Natl Inst Hlth & Welf, Helsinki, Finland.
[Homuth, Georg] Ernst Moritz Arndt Univ Greifswald, Interfaculty Inst Genet & Funct Genom, Greifswald, Germany.
[Kemp, John P.; Evans, David M.] Univ Queensland, Diamantina Inst, Translat Res Inst, Brisbane, Qld, Australia.
[Magri, Chiara; Minelli, Alessandra] Univ Brescia, Dept Mol & Translat Med, Brescia, Italy.
[Mihailov, Evelin] Univ Tartu, Dept Biotechnol, EE-50090 Tartu, Estonia.
[Milaneschi, Yuri; Penninx, BrendaW. J. H.] Vrije Univ Amsterdam, Med Ctr, EMGO Inst Neurosci Campus Amsterdam, Dept Psychiat, Amsterdam, Netherlands.
[Nauck, Matthias] Univ Med Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany.
[Palotie, Aarno] Wellcome Trust Genome Campus, Wellcome Trust Sanger Inst, Cambridge, England.
[Palotie, Aarno; Widen, Elisabeth; Kaprio, Jaakko] Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland.
[Polasek, Ozren] Univ Split, Fac Med, Dept Publ Hlth, Split, Croatia.
[Raitakari, Olli T.] Turku Univ Hosp, Dept Clin Physiol & Nucl Med, FIN-20520 Turku, Finland.
[Raitakari, Olli T.] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland.
[Rose, Richard J.] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN USA.
[Slutske, Wendy S.] Univ Missouri, Dept Psychol Sci, Columbia, MO 65211 USA.
[Slutske, Wendy S.] Univ Missouri, Missouri Alcoholism Res Ctr, Columbia, MO 65211 USA.
[Starr, John M.] Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh, Midlothian, Scotland.
[St Pourcain, Beate] Univ Bristol, Sch Oral & Dent Sci, Bristol, Avon, England.
[St Pourcain, Beate] Univ Bristol, Sch Expt Psychol, Bristol, Avon, England.
[Sutin, Angelina R.; Terracciano, Antonio] Florida State Univ, Coll Med, Tallahassee, FL 32306 USA.
[Vermeulen, Sita] Radboud Univ Nijmegen, Med Ctr, Dept Hlth Evidence, NL-6525 ED Nijmegen, Netherlands.
[Zgaga, Lina] Univ Dublin Trinity Coll, Dept Publ Hlth & Primary Care, Dublin 2, Ireland.
[Porteous, David] Univ Edinburgh, Med Genet Sect, Ctr Genom & Expt Med, Inst Genet & Mol Med,Western Gen Hosp, Edinburgh, Midlothian, Scotland.
[Hayward, Caroline] Univ Edinburgh, Generat Scotland, Ctr Genom & Expt Med, Inst Genet & Mol Med,Western Gen Hosp, Edinburgh, Midlothian, Scotland.
[Grabe, Hans J.] HELIOS Hosp Stralsund, Dept Psychiat & Psychotherapy, Stralsund, Germany.
[McGue, Matt] Univ Southern Denmark, Inst Publ Hlth, Odense, Denmark.
RP de Moor, MHM (reprint author), Vrije Univ Amsterdam, Dept Clin Child & Family Studies, Van der Boechorststr 1, NL-1081 BT Amsterdam, Netherlands.
EM m.h.m.de.moor@vu.nl
RI Polasek, Ozren/B-6002-2011; Arias Vasquez, Alejandro/E-4762-2012;
Franke, Barbara/D-4836-2009; Jokela, Markus/A-4669-2009; ruggiero,
daniela/K-5638-2016; Realo, Anu/M-9524-2016; Luciano,
Michelle/F-7277-2010; Hansell, Narelle/A-4553-2016; Davey Smith,
George/A-7407-2013; Magnusson, Patrik/C-4458-2017
OI Evans, David/0000-0003-0663-4621; Kaprio, Jaakko/0000-0002-3716-2455;
Medland, Sarah/0000-0003-1382-380X; Timpson,
Nicholas/0000-0002-7141-9189; Karlsson, Robert/0000-0002-8949-2587;
Heinonen, Kati/0000-0002-1262-5599; Lahti, Jari/0000-0002-4310-5297;
Raikkonen, Katri/0000-0003-3124-3470; Ouwens,
Klaasjan/0000-0002-3864-7710; Zgaga, Lina/0000-0003-4089-9703; Allik,
Juri/0000-0002-8358-4747; Esko, Tonu/0000-0003-1982-6569; NUTILE,
TERESA/0000-0001-7062-8352; Viktorin, Alexander/0000-0003-2141-2816;
Wedenoja, Juho/0000-0002-6155-0378; Wright,
Margaret/0000-0001-7133-4970; Eriksson, Johan/0000-0002-2516-2060; Kemp,
John/0000-0002-9105-2249; Polasek, Ozren/0000-0002-5765-1862; Derringer,
Jaime/0000-0002-7352-9859; Arias Vasquez, Alejandro/0000-0002-4786-0169;
Franke, Barbara/0000-0003-4375-6572; Latvala, Antti/0000-0001-5695-117X;
Jokela, Markus/0000-0003-0117-0012; ruggiero,
daniela/0000-0003-3898-7827; Luciano, Michelle/0000-0003-0935-7682;
Hansell, Narelle/0000-0002-8229-9741; Davey Smith,
George/0000-0002-1407-8314;
FU German Research Foundation; German Federal Ministry of Education and
Research; DAMP Foundation
FX Dr Grabe reported having received funding by the German Research
Foundation, the German Federal Ministry of Education and Research, and
the DAMP Foundation as well as speaker's honoraria from Servier and Eli
Lilly and Co. No other disclosures were reported.
NR 67
TC 37
Z9 37
U1 10
U2 24
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-622X
EI 2168-6238
J9 JAMA PSYCHIAT
JI JAMA Psychiatry
PD JUL
PY 2015
VL 72
IS 7
BP 642
EP 650
DI 10.1001/jamapsychiatry.2015.0554
PG 9
WC Psychiatry
SC Psychiatry
GA DA1PQ
UT WOS:000367568100004
ER
PT J
AU Schmidt, PJ
Ben Dor, R
Martinez, PE
Guerrieri, GM
Harsh, VL
Thompson, K
Koziol, DE
Nieman, LK
Rubinow, DR
AF Schmidt, Peter J.
Ben Dor, Rivka
Martinez, Pedro E.
Guerrieri, Gioia M.
Harsh, Veronica L.
Thompson, Karla
Koziol, Deloris E.
Nieman, Lynnette K.
Rubinow, David R.
TI Effects of Estradiol Withdrawal on Mood in Women With Past
Perimenopausal Depression A Randomized Clinical Trial
SO JAMA PSYCHIATRY
LA English
DT Article
ID HORMONE REPLACEMENT THERAPY; ESTROGEN RECEPTOR-BETA; FORCED SWIM TEST;
MENOPAUSAL TRANSITION; POSTPARTUM DEPRESSION; GONADAL-STEROIDS;
MENSTRUAL CYCLES; HOT FLASHES; NATION SWAN; SYMPTOMS
AB IMPORTANCE Perimenopause is accompanied by an increased risk of new and recurrent depression. The coincidence of declining ovarian function with the onset of depression led to the inference that "withdrawal" from physiologic estradiol levels underpinned depression in perimenopause. To our knowledge, this is the first controlled systematic study to directly test the estrogen withdrawal theory of perimenopausal depression (PMD).
OBJECTIVE To examine the role of estradiol withdrawal in PMD.
DESIGN, SETTING, AND PARTICIPANTS Initial open-label treatment with estradiol followed by randomized, double-blind, placebo-controlled, parallel-design evaluation of continued estradiol treatment was evaluated at an outpatient research facility at the National Institutes of Health Clinical Center. An intent-to-treat analysis was performed between October 2003 and July 2012. Participants included asymptomatic postmenopausal women with past PMD responsive to hormone therapy (n = 26) and asymptomatic postmenopausal women with no history of depression (n = 30) matched for age, body mass index, and reproductive status who served as controls. Data were analyzed between November 2012 and October 2013 by repeated-measures analysis of variance.
INTERVENTIONS After 3 weeks of open-label administration of transdermal estradiol (100 mu g/d), participants were randomized to a parallel design to receive either estradiol (100 mu g/d; 27 participants) or matched placebo skin patches (29 participants) for 3 additional weeks under double-blind conditions.
MAIN OUTCOMES AND MEASURES Center for Epidemiologic Studies-Depression Scale and 17-item Hamilton Depression Rating Scale (completed by raters blind to diagnosis and randomization status), self-administered visual analog symptom ratings, and blood hormone levels obtained at weekly clinic visits.
RESULTS None of the women reported depressive symptoms during open-label use of estradiol. Women with past PMD who were crossed over from estradiol to placebo experienced a significant increase in depression symptom severity demonstrated using the Center for Epidemiologic Studies-Depression Scale and 17-item Hamilton Depression Rating Scale, with mean (SD) scores increasing from estradiol (ie, 2.4 [2.0] and 3.0 [2.5]) to placebo (8.8 [4.9] and 6.6 [4.5], respectively [P = .0004 for both]). Women with past PMD who continued estradiol therapy and all women in the control group remained asymptomatic. Women in both groups had similar hot-flush severity and plasma estradiol levels during use of placebo.
CONCLUSIONS AND RELEVANCE In women with past PMD that was previously responsive to hormone therapy, the recurrence of depressive symptoms during blinded hormone withdrawal suggests that normal changes in ovarian estradiol secretion can trigger an abnormal behavioral state in these susceptible women. Women with a history of PMD should be alert to the risk of recurrent depression when discontinuing hormone therapy.
C1 [Schmidt, Peter J.; Ben Dor, Rivka; Martinez, Pedro E.; Guerrieri, Gioia M.; Thompson, Karla] NIMH, Sect Behav Endocrinol, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Harsh, Veronica L.] Univ Virginia, Dept Psychiat & Neurobehav Sci, Charlottesville, VA USA.
[Koziol, Deloris E.] NIH, Biostat & Clin Epidemiol Serv, Ctr Clin, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Nieman, Lynnette K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Intramural Res Program Reprod & Adult Endocrinol, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
[Rubinow, David R.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA.
RP Schmidt, PJ (reprint author), NIMH, Sect Behav Endocrinol, Dept Hlth & Human Serv, Bldg 10CRC,Room 25330,10 Ctr Dr,Mail Stop Code 12, Bethesda, MD 20892 USA.
EM peterschmidt@mail.nih.gov
FU Intramural Research Program of the National Institute of Mental Health
(NIMH), National Institutes of Health (NIH)
FX This research was supported by the Intramural Research Program of the
National Institute of Mental Health (NIMH), National Institutes of
Health (NIH). Novartis Pharmaceuticals supplied estradiol skin patches
(Vivelle-Dot) and matched placebos for this study.
NR 48
TC 11
Z9 11
U1 1
U2 5
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-622X
EI 2168-6238
J9 JAMA PSYCHIAT
JI JAMA Psychiatry
PD JUL
PY 2015
VL 72
IS 7
BP 714
EP 726
DI 10.1001/jamapsychiatry.2015.0111
PG 13
WC Psychiatry
SC Psychiatry
GA DA1PQ
UT WOS:000367568100012
PM 26018333
ER
PT J
AU Shrader, JA
Kats, I
Kokkinis, A
Zampieri, C
Levy, E
Joe, GO
Woolstenhulme, JG
Drinkard, BE
Smith, MR
Ching, W
Ghosh, L
Fox, D
Auh, S
Schindler, AB
Fischbeck, KH
Grunseich, C
AF Shrader, Joseph A.
Kats, Ilona
Kokkinis, Angela
Zampieri, Cris
Levy, Ellen
Joe, Galen O.
Woolstenhulme, Joshua G.
Drinkard, Bart E.
Smith, Michaele R.
Ching, Willie
Ghosh, Laboni
Fox, Derrick
Auh, Sungyoung
Schindler, Alice B.
Fischbeck, Kenneth H.
Grunseich, Christopher
TI A randomized controlled trial of exercise in spinal and bulbar muscular
atrophy
SO ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
LA English
DT Article
ID ANDROGEN RECEPTOR; NEUROMUSCULAR DISEASES; RESISTANCE EXERCISE;
PERCEIVED EXERTION; NORMATIVE VALUES; PERFORMANCE; VALIDATION;
INTENSITY; STRENGTH; PEOPLE
AB Objective: To determine the safety and efficacy of a home-based functional exercise program in spinal and bulbar muscular atrophy (SBMA). Methods: Subjects were randomly assigned to participate in 12 weeks of either functional exercises (intervention) or a stretching program (control) at the National Institutes of Health in Bethesda, MD. A total of 54 subjects enrolled, and 50 completed the study with 24 in the functional exercise group and 26 in the stretching control group. The primary outcome measure was the Adult Myopathy Assessment Tool (AMAT) total score, and secondary measures included total activity by accelerometry, muscle strength, balance, timed up and go, sit-to-stand test, health-related quality of life, creatine kinase, and insulin-like growth factor-1. Results: Functional exercise was well tolerated but did not lead to significant group differences in the primary outcome measure or any of the secondary measures. The functional exercise did not produce significantly more adverse events than stretching, and was not perceived to be difficult. To determine whether a subset of the subjects may have benefited, we divided them into high and low functioning based on baseline AMAT scores and performed a post hoc subgroup analysis. Low-functioning individuals receiving the intervention increased AMAT functional subscale scores compared to the control group. Interpretation: Although these trial results indicate that functional exercise had no significant effect on total AMAT scores or on mobility, strength, balance, and quality of life, post hoc findings indicate that low-functioning men with SBMA may respond better to functional exercises, and this warrants further investigation with appropriate exercise intensity.
C1 [Shrader, Joseph A.; Zampieri, Cris; Levy, Ellen; Joe, Galen O.; Woolstenhulme, Joshua G.; Drinkard, Bart E.; Smith, Michaele R.; Ching, Willie] NIH, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA.
[Kats, Ilona; Kokkinis, Angela; Ghosh, Laboni; Fox, Derrick; Schindler, Alice B.; Fischbeck, Kenneth H.; Grunseich, Christopher] NINDS, Neurogenet Branch, Bethesda, MD 20892 USA.
[Auh, Sungyoung] NINDS, Clin Neurosci Program, Bethesda, MD 20892 USA.
RP Grunseich, C (reprint author), NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA.
EM christopher.grunseich@nih.gov
NR 32
TC 7
Z9 7
U1 1
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2328-9503
J9 ANN CLIN TRANSL NEUR
JI Ann. Clin. Transl. Neurol.
PD JUL
PY 2015
VL 2
IS 7
BP 739
EP 747
DI 10.1002/acn3.208
PG 9
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CZ6UC
UT WOS:000367235500003
PM 26273686
ER
PT J
AU Goetzl, EJ
Boxer, A
Schwartz, JB
Abner, EL
Petersen, RC
Miller, BL
Carlson, OD
Mustapic, M
Kapogiannis, D
AF Goetzl, Edward J.
Boxer, Adam
Schwartz, Janice B.
Abner, Erin L.
Petersen, Ronald C.
Miller, Bruce L.
Carlson, Olga D.
Mustapic, Maja
Kapogiannis, Dimitrios
TI Low neural exosomal levels of cellular survival factors in Alzheimer's
disease
SO ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
LA English
DT Article
ID CLINICAL-TRIALS; BLOOD EXOSOMES; ADAS-COG; DIAGNOSIS; CRITERIA
AB Transcription factors that mediate neuronal defenses against diverse stresses were quantified in plasma neural-derived exosomes of Alzheimer's disease or frontotemporal dementia patients and matched controls. Exosomal levels of low-density lipoprotein receptor-related protein 6, heat-shock factor-1, and repressor element 1-silencing transcription factor all were significantly lower in Alzheimer's disease patients than controls (P < 0.0001). In frontotemporal dementia, the only significant difference was higher levels of repressor element 1-silencing transcription factor than in controls. Exosomal transcription factors were diminished 2-10 years before clinical diagnosis of Alzheimer's disease. Low exosomal levels of survival proteins may explain decreased neuronal resistance to Alzheimer's disease neurotoxic proteins.
C1 [Goetzl, Edward J.] UCSF Med Ctr, Dept Med, San Francisco, CA USA.
[Goetzl, Edward J.; Schwartz, Janice B.] Jewish Home San Francisco, San Francisco, CA USA.
[Boxer, Adam; Miller, Bruce L.] UCSF Med Ctr, Dept Neurol, Memory & Aging Ctr, San Francisco, CA USA.
[Schwartz, Janice B.] UCSF Med Ctr, Dept Med, San Francisco, CA USA.
[Schwartz, Janice B.] UCSF Med Ctr, Dept Bioengn, San Francisco, CA USA.
[Abner, Erin L.] Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA.
[Petersen, Ronald C.] Mayo Clin, Dept Neurol, Rochester, MN USA.
[Carlson, Olga D.; Mustapic, Maja; Kapogiannis, Dimitrios] NIA, Intramural Res Program, Baltimore, MD 21224 USA.
RP Goetzl, EJ (reprint author), 1719 Broderick St, San Francisco, CA 94115 USA.
EM edward.goetzl@ucsf.edu; kapogiannisd@mail.nih.gov
FU NIA NIH HHS [P30 AG028383, R01 AG038791, P50 AG023501]; NINDS NIH HHS
[U54 NS092089]
NR 20
TC 8
Z9 8
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2328-9503
J9 ANN CLIN TRANSL NEUR
JI Ann. Clin. Transl. Neurol.
PD JUL
PY 2015
VL 2
IS 7
BP 769
EP 773
DI 10.1002/acn3.211
PG 5
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CZ6UC
UT WOS:000367235500006
PM 26273689
ER
PT J
AU Resnik, DB
AF Resnik, David B.
TI Addressing diversion effects
SO JOURNAL OF LAW AND THE BIOSCIENCES
LA English
DT Editorial Material
DE research ethics; principles; diversion effects
AB Alan Wertheimer argues that those who promulgate principles of research ethics have a responsibility to take into account the diversion effects of those principles. In this commentary, I argue that Wertheimer's proposal that diversion effects should be considered when promulgating principles of research ethics makes sense, but it often may be best to deal with these effects once a principle has been accepted and implemented, rather than focusing on them at the outset.
C1 [Resnik, David B.] NIEHS, NIH, Durham, NC 27709 USA.
RP Resnik, DB (reprint author), NIEHS, NIH, Durham, NC 27709 USA.
EM resnikd@niehs.nih.gov
NR 8
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 2053-9711
J9 J LAW BIOSCI
JI J. Law Biosci.
PD JUL
PY 2015
VL 2
IS 2
BP 428
EP 430
DI 10.1093/jlb/lsv012
PG 3
WC Law
SC Government & Law
GA CY6IG
UT WOS:000366511800011
PM 27774202
ER
PT J
AU dos Reis, FJC
Lynn, S
Ali, HR
Eccles, D
Hanby, A
Provenzano, E
Caldas, C
Howat, WJ
McDuffus, LA
Liu, B
Daley, F
Coulson, P
Vyas, RJ
Harris, LM
Owens, JM
Carton, AFM
McQuillan, JP
Paterson, AM
Hirji, Z
Christie, SK
Holmes, AR
Schmidt, MK
Garcia-Closas, M
Easton, DF
Bolla, MK
Wang, Q
Benitez, J
Milne, RL
Mannermaa, A
Couch, F
Devilee, P
Tollenaar, RAEM
Seynaeve, C
Cox, A
Cross, SS
Blows, FM
Sanders, J
de Groot, R
Figueroa, J
Sherman, M
Hooning, M
Brenner, H
Holleczek, B
Stegmaier, C
Lintott, C
Pharoah, PDP
AF Candido dos Reis, Francisco J.
Lynn, Stuart
Ali, H. Raza
Eccles, Diana
Hanby, Andrew
Provenzano, Elena
Caldas, Carlos
Howat, William J.
McDuffus, Leigh-Anne
Liu, Bin
Daley, Frances
Coulson, Penny
Vyas, Rupesh J.
Harris, Leslie M.
Owens, Joanna M.
Carton, Amy F. M.
McQuillan, Janette P.
Paterson, Andy M.
Hirji, Zohra
Christie, Sarah K.
Holmes, Amber R.
Schmidt, Marjanka K.
Garcia-Closas, Montserrat
Easton, Douglas F.
Bolla, Manjeet K.
Wang, Qin
Benitez, Javier
Milne, Roger L.
Mannermaa, Arto
Couch, Fergus
Devilee, Peter
Tollenaar, Robert A. E. M.
Seynaeve, Caroline
Cox, Angela
Cross, Simon S.
Blows, Fiona M.
Sanders, Joyce
de Groot, Renate
Figueroa, Jonine
Sherman, Mark
Hooning, Maartje
Brenner, Hermann
Holleczek, Bernd
Stegmaier, Christa
Lintott, Chris
Pharoah, Paul D. P.
TI Crowdsourcing the General Public for Large Scale Molecular Pathology
Studies in Cancer
SO EBIOMEDICINE
LA English
DT Article
DE Citizen science; Crowd science; Crowdsourcing; Breast cancer
ID BREAST-CANCER; TISSUE MICROARRAYS; ESTROGEN-RECEPTOR; MISSING DATA;
ASSOCIATION; IMMUNOHISTOCHEMISTRY; BIOMARKERS; SURVIVAL
AB Background: Citizen science, scientific research conducted by non-specialists, has the potential to facilitate biomedical research using available large-scale data, however validating the results is challenging. The Cell Slider is a citizen science project that intends to share images from tumors with the general public, enabling them to score tumor markers independently through an internet-based interface.
Methods: From October 2012 to June 2014, 98,293 Citizen Scientists accessed the Cell Slider web page and scored 180,172 sub-images derived from images of 12,326 tissue microarray cores labeled for estrogen receptor (ER). We evaluated the accuracy of Citizen Scientist's ER classification, and the association between ER status and prognosis by comparing their test performance against trained pathologists.
Findings: The area under ROC curve was 0.95 (95% CI 0.94 to 0.96) for cancer cell identification and 0.97 (95% CI 0.96 to 0.97) for ER status. ER positive tumors scored by Citizen Scientists were associated with survival in a similar way to that scored by trained pathologists. Survival probability at 15 years were 0.78 (95% CI 0.76 to 0.80) for ER-positive and 0.72 (95% CI 0.68 to 0.77) for ER-negative tumors based on Citizen Scientists classification. Based on pathologist classification, survival probability was 0.79 (95% CI 0.77 to 0.81) for ER-positive and 0.71 (95% CI 0.67 to 0.74) for ER-negative tumors. The hazard ratio for death was 0.26 (95% CI 0.18 to 0.37) at diagnosis and became greater than one after 6.5 years of follow-up for ER scored by Citizen Scientists, and 0.24 (95% CI 0.18 to 0.33) at diagnosis increasing thereafter to one after 6.7 (95% CI 4.1 to 10.9) years of follow-up for ER scored by pathologists.
Interpretation: Crowdsourcing of the general public to classify cancer pathology data for research is viable, engages the public and provides accurate ER data. Crowdsourced classification of research data may offer a valid solution to problems of throughput requiring human input. (C) 2015 The Authors. Published by Elsevier B. V.
C1 [Candido dos Reis, Francisco J.; Easton, Douglas F.; Blows, Fiona M.; Pharoah, Paul D. P.] Univ Cambridge, Dept Oncol, Cambridge CB1 8RN, England.
[Candido dos Reis, Francisco J.] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Gynecol & Obstet, BR-14049 Ribeirao Preto, Brazil.
[Lynn, Stuart; Lintott, Chris] Univ Oxford, Dept Phys Astrophys, Oxford, England.
[Ali, H. Raza; Caldas, Carlos; Howat, William J.; McDuffus, Leigh-Anne; Liu, Bin] Cambridge Inst, Canc Res UK, Cambridge, England.
[Eccles, Diana] Univ Southampton, Southampton, Hants, England.
[Hanby, Andrew] Univ Leeds, Leeds, W Yorkshire, England.
[Provenzano, Elena] Addenbrookes Hosp NHS Trust, Cambridge, England.
[Daley, Frances; Coulson, Penny; Garcia-Closas, Montserrat] Inst Canc Res, London SW3 6JB, England.
[Vyas, Rupesh J.; Harris, Leslie M.; Owens, Joanna M.; Carton, Amy F. M.; McQuillan, Janette P.; Paterson, Andy M.; Hirji, Zohra; Christie, Sarah K.; Holmes, Amber R.] Canc Res UK, London, England.
[Schmidt, Marjanka K.; Sanders, Joyce; de Groot, Renate] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands.
[Easton, Douglas F.; Bolla, Manjeet K.; Wang, Qin; Pharoah, Paul D. P.] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
[Benitez, Javier] Spanish Natl Canc Res Ctr CNIO, Human Canc Genet Program, Human Genotyping CEGEN Unit, Madrid, Spain.
[Benitez, Javier] Biomed Network Rare Dis CIBERER, Madrid, Spain.
[Milne, Roger L.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
[Milne, Roger L.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic 3010, Australia.
[Mannermaa, Arto] Univ Eastern Finland, Inst Clin Med Pathol & Forens Med, Joensuu, Finland.
[Couch, Fergus] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
[Devilee, Peter] Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands.
[Devilee, Peter] Leiden Univ, Med Ctr, Dept Pathol, Leiden, Netherlands.
[Tollenaar, Robert A. E. M.] Leiden Univ, Med Ctr, Dept Surg Oncol, Leiden, Netherlands.
[Cox, Angela] Univ Sheffield, Dept Oncol, Sheffield Canc Res, Sheffield, S Yorkshire, England.
[Cross, Simon S.] Univ Sheffield, Dept Neurosci, Acad Unit Pathol, Sheffield, S Yorkshire, England.
[Figueroa, Jonine; Sherman, Mark] NCI, Bethesda, MD 20892 USA.
[Seynaeve, Caroline; Hooning, Maartje] Erasmus MC Canc Inst, Family Canc Clin, Dept Med Oncol, Rotterdam, Netherlands.
[Brenner, Hermann] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
[Brenner, Hermann] German Canc Res Ctr, Div Prevent Oncol, Heidelberg, Germany.
[Brenner, Hermann] German Canc Res Ctr, German Canc Consortium DKTK, Heidelberg, Germany.
[Holleczek, Bernd; Stegmaier, Christa] Saarland Canc Registry, Saarbrucken, Germany.
RP Pharoah, PDP (reprint author), Univ Cambridge, Dept Oncol, Worths Causeway, Cambridge CB1 8RN, England.
EM pp10001@medschl.cam.ac.uk
RI Candido dos Reis, Francisco/K-7024-2016;
OI Candido dos Reis, Francisco/0000-0001-5758-5917; Cross,
Simon/0000-0003-2044-1754; Cox, Angela/0000-0002-5138-1099
NR 24
TC 4
Z9 4
U1 1
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 2352-3964
J9 EBIOMEDICINE
JI EBioMedicine
PD JUL
PY 2015
VL 2
IS 7
BP 681
EP 689
DI 10.1016/j.ebiom.2015.05.009
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA CX8LB
UT WOS:000365953900020
ER
PT J
AU Britton, JC
Suway, JG
Clementi, MA
Fox, NA
Pine, DS
Bar-Haim, Y
AF Britton, Jennifer C.
Suway, Jenna G.
Clementi, Michelle A.
Fox, Nathan A.
Pine, Daniel S.
Bar-Haim, Yair
TI Neural changes with attention bias modification for anxiety: a
randomized trial
SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE
LA English
DT Article
DE attention training; dot-probe; fMRI; amygdala; anxiety; treatment
ID PREFRONTAL CORTEX ACTIVATION; COGNITIVE-BEHAVIORAL THERAPY; GENERALIZED
SOCIAL PHOBIA; FACIAL EXPRESSIONS; PEDIATRIC ANXIETY; ANGRY FACES;
SELF-REPORT; DISORDER; THREAT; AMYGDALA
AB Attention bias modification (ABM) procedures typically reduce anxiety symptoms, yet little is known about the neural changes associated with this behavioral treatment. Healthy adults with high social anxiety symptoms (n = 53) were randomized to receive either active or placebo ABM. Unlike placebo ABM, active ABM aimed to train individuals' attention away from threat. Using the dot-probe task, threat-related attention bias was measured during magnetic resonance imaging before and after acute and extended training over 4 weeks. A subset of participants completed all procedures (n = 30, 15 per group). Group differences in neural activation were identified using standard analyses. Linear regression tested predictive factors of symptom reduction (i.e., training group, baseline indices of threat bias). The active and placebo groups exhibited different patterns of right and left amygdala activation with training. Across all participants irrespective of group, individuals with greater left amygdala activation in the threat-bias contrast prior to training exhibited greater symptom reduction. After accounting for baseline amygdala activation, greater symptom reduction was associated with assignment to the active training group. Greater left amygdala activation at baseline predicted reductions in social anxiety symptoms following ABM. Further research is needed to clarify brain-behavior mechanisms associated with ABM training.
C1 [Britton, Jennifer C.; Clementi, Michelle A.; Pine, Daniel S.] NIMH, Sect Dev & Affect Neurosci, Bethesda, MD 20892 USA.
[Britton, Jennifer C.] Univ Miami, Dept Psychol, Coral Gables, FL 33146 USA.
[Suway, Jenna G.; Fox, Nathan A.] Univ Maryland, Dept Human Dev & Quantitat Methodol, College Pk, MD 20742 USA.
[Suway, Jenna G.] Univ Calif San Diego, San Diego State Univ, Joint Doctoral Program Clin Psychol, San Diego, CA 92120 USA.
[Clementi, Michelle A.] Univ Houston, Dept Psychol, Houston, TX 77204 USA.
[Bar-Haim, Yair] Tel Aviv Univ, Sch Psychol Sci, IL-69978 Tel Aviv, Israel.
[Bar-Haim, Yair] Tel Aviv Univ, Sagol Sch Neurosci, IL-69978 Tel Aviv, Israel.
RP Britton, JC (reprint author), Univ Miami, Dept Psychol, 5665 Ponce de Leon Blvd,Flipse Bldg, Coral Gables, FL 33146 USA.
EM j.britton@miami.edu
FU Intramural Research Program of the National Institute of Mental Health,
National Institutes of Health [P50 MH078105]; Brain & Behavior Research
Foundation; [R00 MH091183]
FX This work was supported in part by the Intramural Research Program of
the National Institute of Mental Health, National Institutes of Health
(P50 MH078105 to J.G.S.), and the Brain & Behavior Research Foundation,
formerly the National Alliance of Research on Schizophrenia and
Depression (NARSAD) (2009 Young Investigator to J.C.B.). In addition,
J.C.B. was supported by R00 MH091183.
NR 50
TC 8
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U1 6
U2 17
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1749-5016
EI 1749-5024
J9 SOC COGN AFFECT NEUR
JI Soc. Cogn. Affect. Neurosci.
PD JUL
PY 2015
VL 10
IS 7
BP 913
EP 920
DI 10.1093/scan/nsu141
PG 8
WC Neurosciences; Psychology; Psychology, Experimental
SC Neurosciences & Neurology; Psychology
GA CX2PH
UT WOS:000365538600004
PM 25344944
ER
PT J
AU Angelousi, A
Fencl, F
Faucz, FR
Malikova, J
Sumnik, Z
Lebl, J
Stratakis, CA
AF Angelousi, Anna
Fencl, Filip
Faucz, Fabio R.
Malikova, Jana
Sumnik, Zdenek
Lebl, Jan
Stratakis, Constantine A.
TI McCune Albright syndrome and bilateral adrenal hyperplasia: the GNAS
mutation may only be present in adrenal tissue
SO HORMONES-INTERNATIONAL JOURNAL OF ENDOCRINOLOGY AND METABOLISM
LA English
DT Article
DE Bilateral adrenocortical hyperplasia; Cushing syndrome; Primary
pigmented nodular adrenocortical disease; PRKAR1A; Protein kinase A
ID CUSHINGS-SYNDROME; GS
AB OBJECTIVE: Corticotropin (ACTH)-independent hypercortisolism due to bilateral adrenocortical hyperplasia (BAH) in infancy is an extremely rare condition that is often caused by McCune Albright syndrome (MAS). MAS is caused by an activating mutation of the GNAS gene which leads to increased cyclic (c) adenosine monophosphate (AMP) signaling. Most forms of BAH are linked to increased cAMP signaling. We report the case of an infant with MAS who had BAH. METHODS: Genomic DNA fragments from blood and adrenal tissue encompassing regions (exons 8 and 9) with the hot spot activating missense GNAS mutations were amplified by classical bidirectional Sanger sequencing. RESULTS: The infant was found to carry the most common GNAS mutation, in exon 8 (c.602G>A, p. R201H), only in her adrenocortical tissue, despite extensive skin and other findings. CONCLUSIONS: We conclude that infants with MAS, despite absence of the GNAS activating mutation in blood, may still have significant clinical findings, including ACTH-independent hypercortisolism. Molecular confirmation of the diagnosis should be sought at the tissue level in these patients.
C1 [Angelousi, Anna; Faucz, Fabio R.; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
[Fencl, Filip; Malikova, Jana; Sumnik, Zdenek; Lebl, Jan] Univ Hosp Motol, Dept Pediat, Prague, Czech Republic.
RP Faucz, FR (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH,CRC,East Labs, Room 1-3216,10 Ctr Dr, Bethesda, MD 20892 USA.
EM fabio.faucz@nih.gov
RI Lebl, Jan/D-9563-2017
OI Lebl, Jan/0000-0002-3365-5375
FU Intramural Research Program of the National Institutes of Health, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development; Greek State Foundation for Scholarships (IKY)
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, Eunice Kennedy Shriver National Institute
of Child Health and Human Development (Clinical trial registration
number of NCT00005927) and in part by the Greek State Foundation for
Scholarships (IKY).
NR 10
TC 0
Z9 0
U1 0
U2 1
PU HELLENIC ENDOCRINE SOC
PI ATHENS
PA 14 ALEXANDRAS AVE, ATHENS, 106 82, GREECE
SN 1109-3099
J9 HORM-INT J ENDOCRINO
JI Horm.-Int. J. Endocrinol. Metab.
PD JUL-SEP
PY 2015
VL 14
IS 3
BP 447
EP 450
DI 10.14310/horm.2002.1578
PG 4
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CW6FG
UT WOS:000365092400015
PM 26188235
ER
PT J
AU Muralidharan, P
Malapit, M
Mallory, E
Hayes, D
Mansour, HM
AF Muralidharan, Priya
Malapit, Monica
Mallory, Evan
Hayes, Don, Jr.
Mansour, Heidi M.
TI Inhalable nanoparticulate powders for respiratory delivery
SO NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
LA English
DT Review
DE Pulmonary nanomedicine; Solid-state; Dry powder inhaler; Particle
engineering design; Inhalation powders; Lung/nasal
ID AEROSOL DISPERSION PERFORMANCE; PULMONARY DRUG-DELIVERY; POLYMER HYBRID
NANOPARTICLES; DRY-POWDER; PHYSICOCHEMICAL CHARACTERIZATION;
NANOCOMPOSITE PARTICLES; INHALATION AEROSOLS; NASAL DELIVERY;
DIPALMITOYLPHOSPHATIDYLCHOLINE DPPC; MULTIFUNCTIONAL PARTICLES
AB Nanoparticles are extensively studied for drug delivery and are proving to be effective in drug delivery and the diagnostic field. Drug delivery to lungs has its advantages over other routes of administration. Inhalable powders consisting of nanoparticles are gaining much interest in respiratory research and clinical therapy. Particle engineering technique is a key factor to develop inhalable formulations that can successfully deliver drug with improved therapeutic effect and enhanced targeting. Inhalable nanoparticles in the solid-state dry powders for targeted pulmonary delivery offer unique advantages and are an exciting new area of research. Nasal delivery of inhalable nanoparticulate powders is gaining research attention recently, particularly in vaccine applications, systemic drug delivery in the treatment of pain, and noninvasive brain targeting. Fundamental aspects and recent advancements along with future prospects of inhalable powders consisting of nanoparticles in the solid-state for respiratory delivery are presented.
From the Clinical Editor: The advance in nanotechnology has enabled the design of new drug delivery systems through inhalation, which has many advantages over traditional delivery systems. This comprehensive review describes and discusses the current status, drug design and modification for targeted delivery and challenges of the use of nanoparticles in the respiratory tract. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Muralidharan, Priya; Malapit, Monica; Mallory, Evan; Mansour, Heidi M.] Univ Arizona, Coll Pharm, Skaggs Pharmaceut Sci Ctr, Tucson, AZ 85721 USA.
[Hayes, Don, Jr.] Ohio State Univ, Coll Med, Dept Pediat, Columbus, OH 43210 USA.
[Hayes, Don, Jr.] Ohio State Univ, Coll Med, Dept Internal Med, Lung & Heart Lung Transplant Programs, Columbus, OH 43210 USA.
[Hayes, Don, Jr.] Ohio State Univ, Coll Med, Davis Heart & Lung Res Inst, Columbus, OH 43210 USA.
[Mansour, Heidi M.] Univ Arizona, Res Inst BIO5, Tucson, AZ USA.
[Mansour, Heidi M.] Univ Arizona, Inst Environm, Tucson, AZ USA.
[Mansour, Heidi M.] Univ Arizona, Ctr Comprehens Canc, NCI, Tucson, AZ USA.
RP Mansour, HM (reprint author), Univ Arizona, Coll Pharm, Skaggs Pharmaceut Sci Ctr, Tucson, AZ 85721 USA.
EM mansour@pharmacy.arizona.edu
FU University of Arizona, Tucson, AZ, USA; National Institutes of Health
NIAID [HHSN2272201000033I, HHSN27200002 A65]
FX The authors acknowledge The College of Pharmacy Graduate Fellowship (The
University of Arizona, Tucson, AZ, USA) awarded to P.M. and federal
funding to H.M.M. from the National Institutes of Health NIAID
(HHSN2272201000033I, HHSN27200002 A65).
NR 91
TC 10
Z9 10
U1 10
U2 31
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1549-9634
EI 1549-9642
J9 NANOMED-NANOTECHNOL
JI Nanomed.-Nanotechnol. Biol. Med.
PD JUL
PY 2015
VL 11
IS 5
BP 1189
EP 1199
DI 10.1016/j.nano.2015.01.007
PG 11
WC Nanoscience & Nanotechnology; Medicine, Research & Experimental
SC Science & Technology - Other Topics; Research & Experimental Medicine
GA CV0TU
UT WOS:000363967100016
PM 25659645
ER
PT J
AU Haas, AD
Keiser, O
Balestre, E
Brown, S
Bissagnene, E
Chimbetete, C
Dabis, F
Davies, MA
Hoffmann, CJ
Oyaro, P
Parkes-Ratanshi, R
Reynolds, SJ
Sikazwe, I
Wools-Kaloustian, K
Zannou, DM
Wandeler, G
Egger, M
AF Haas, Andreas D.
Keiser, Olivia
Balestre, Eric
Brown, Steve
Bissagnene, Emmanuel
Chimbetete, Cleophas
Dabis, Francois
Davies, Mary-Ann
Hoffmann, Christopher J.
Oyaro, Patrick
Parkes-Ratanshi, Rosalind
Reynolds, Steven J.
Sikazwe, Izukanji
Wools-Kaloustian, Kara
Zannou, D. Marcel
Wandeler, Gilles
Egger, Matthias
CA IeDEA Southern Africa East Africa
TI Monitoring and switching of first-line antiretroviral therapy in adult
treatment cohorts in sub-Saharan Africa: collaborative analysis
SO LANCET HIV
LA English
DT Article
ID RESOURCE-LIMITED SETTINGS; NON-INFERIORITY TRIAL; TREATMENT FAILURE;
2ND-LINE ART; SOUTH-AFRICA; PREDICTORS; CRITERIA; ROUTINE
AB Background HIV-1 viral load testing is recommended to monitor antiretroviral therapy (ART) but is not universally available. The aim of our study was to assess monitoring of first-line ART and switching to second-line ART in sub-Saharan Africa.
Methods We did a collaborative analysis of cohort studies from 16 countries in east Africa, southern Africa, and west Africa that participate in the international epidemiological database to evaluate AIDS (IeDEA). We included adults infected with HIV-1 who started combination ART between January, 2004, and January, 2013. We defined switching of ART as a change from a non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen to one including a protease inhibitor, with adjustment of one or more nucleoside reverse-transcriptase inhibitors (NRTIs). Virological and immunological failures were defined according to WHO criteria. We calculated cumulative probabilities of switching and hazard ratios with 95% CIs comparing routine viral load monitoring, targeted viral load monitoring, CD4 monitoring, and clinical monitoring, adjusting for programme and individual characteristics.
Findings Of 297 825 eligible patients, 10 352 (3%) switched to second-line ART during 782 412 person-years of follow-up. Compared with CD4 monitoring, hazard ratios for switching were 3.15 (95% CI 2.92-3.40) for routine viral load monitoring, 1.21 (1.13-1.30) for targeted viral load monitoring, and 0.49 (0.43-0.56) for clinical monitoring. Of 6450 patients with confirmed virological failure, 58.0% (95% CI 56.5-59.6) switched by 2 years, and of 15 892 patients with confirmed immunological failure, 19.3% (18.5-20.0) switched by 2 years. Of 10 352 patients who switched, evidence of treatment failure based on one CD4 count or viral load measurement ranged from 86 (32%) of 268 patients with clinical monitoring to 3754 (84%) of 4452 with targeted viral load monitoring. Median CD4 counts at switching were 215 cells per mu L (IQR 117-335) with routine viral load monitoring, but were lower with other types of monitoring (range 114-133 cells per mu L).
Interpretation Overall, few patients switched to second-line ART and switching happened late in the absence of routine viral load monitoring. Switching was more common and happened earlier after initiation of ART with targeted or routine viral load testing.
C1 [Haas, Andreas D.; Keiser, Olivia; Wandeler, Gilles; Egger, Matthias] Univ Bern, Inst Social & Prevent Med, CH-3012 Bern, Switzerland.
[Wandeler, Gilles] Univ Hosp Bern, Dept Infect Dis, CH-3010 Bern, Switzerland.
[Wandeler, Gilles] Univ Bern, CH-3012 Bern, Switzerland.
[Balestre, Eric; Dabis, Francois] Univ Bordeaux, Inst Sante Publ Epidemiol & Dev, INSERM, Ctr Rech,U897,Epidemiol Biostat, Bordeaux, France.
[Brown, Steve; Wools-Kaloustian, Kara] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
[Bissagnene, Emmanuel] Ctr Hosp Univ Treichville, Serv Malad Infect & Trop, Abidjan, Cote Ivoire.
[Chimbetete, Cleophas] Newlands Clin, Harare, Zimbabwe.
[Davies, Mary-Ann; Egger, Matthias] Univ Cape Town, Ctr Infect Dis Epidemiol & Res, ZA-7925 Cape Town, South Africa.
[Hoffmann, Christopher J.] Johns Hopkins Univ, Baltimore, MD USA.
[Hoffmann, Christopher J.] Aurum Inst, Johannesburg, South Africa.
[Oyaro, Patrick] Kenya Govt Med Res Ctr, RCTP FACES Program, Kisumu, Kenya.
[Parkes-Ratanshi, Rosalind] Mulago Hosp Complex, Infect Dis Inst, Kampala, Uganda.
[Reynolds, Steven J.] Rakai Hlth Sci Program, Entebbe, Uganda.
[Reynolds, Steven J.] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Reynolds, Steven J.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Sikazwe, Izukanji] Ctr Infect Dis Res Zambia, Lusaka, Zambia.
[Zannou, D. Marcel] Univ Abomey Calavi, Fac Sci Sante, Cotonou, Benin.
[Zannou, D. Marcel] Ctr Natl Hosp Univ Hubert Koutoukou Maga, Ctr Traitement Ambulatoire, Cotonou, Benin.
RP Egger, M (reprint author), Univ Bern, Inst Social & Prevent Med, CH-3012 Bern, Switzerland.
EM egger@ispm.unibe.ch
RI Wejse, Christian/C-8468-2014;
OI Wejse, Christian/0000-0002-2534-2942; Keiser,
Olivia/0000-0001-8191-2789; Haas, Andreas D./0000-0002-4849-181X;
Cornell, Morna/0000-0001-7149-8799; Hoffmann,
Christopher/0000-0002-9422-0519
FU National Institute of Allergy and Infectious Diseases [5U01-AI069924,
U01AI069911, U01AI069919]; Division of Intramural Research, National
Institute of Allergy and Infectious Diseases; Swiss National Science
Foundation [32333B_131629]
FX We thank all patients who contributed data to this study. This study was
funded by the National Institute of Allergy and Infectious Diseases
(5U01-AI069924, U01AI069911, U01AI069919). SJR was funded by the
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases. OK was funded by the Swiss National Science
Foundation (Ambizione/Prosper grant 32333B_131629).
NR 30
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U1 0
U2 3
PU ELSEVIER INC
PI SAN DIEGO
PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 2352-3018
J9 LANCET HIV
JI Lancet HIV
PD JUL
PY 2015
VL 2
IS 7
BP E271
EP E278
DI 10.1016/S2352-3018(15)00087-9
PG 8
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA CU8LC
UT WOS:000363793000007
PM 26423252
ER
PT J
AU Noguchi, LM
Richardson, BA
Baeten, JM
Hillier, SL
Balkus, JE
Chirenje, ZM
Bunge, K
Ramjee, G
Nair, G
Palanee-Phillips, T
Selepe, P
van der Straten, A
Parikh, UM
Gomez, K
Piper, JM
Watts, DH
Marrazzo, JM
AF Noguchi, Lisa M.
Richardson, Barbra A.
Baeten, Jared M.
Hillier, Sharon L.
Balkus, Jennifer E.
Chirenje, Z. Mike
Bunge, Katherine
Ramjee, Gita
Nair, Gonasagrie
Palanee-Phillips, Thesla
Selepe, Pearl
van der Straten, Ariane
Parikh, Urvi M.
Gomez, Kailazarid
Piper, Jeanna M.
Watts, D. Heather
Marrazzo, Jeanne M.
CA VOICE Study Team
TI Risk of HIV-1 acquisition among women who use different types of
injectable progestin contraception in South Africa: a prospective cohort
study
SO LANCET HIV
LA English
DT Article
ID DEPOT MEDROXYPROGESTERONE ACETATE; HORMONAL CONTRACEPTION; INFECTION;
NORETHISTERONE; TRANSMISSION
AB Background Several observational studies have reported that HIV-1 acquisition seems to be higher in women who use depot medroxyprogesterone acetate (DMPA) than in those who do not use hormonal contraception. We aimed to assess whether two injectable progestin-only contraceptives, DMPA and norethisterone enanthate (NET-EN), confer different risks of HIV-1 acquisition.
Methods We included data from South African women who used injectable contraception while participating in the VOICE study, a multisite, randomised, placebo-controlled trial that investigated the safety and efficacy of three formulations of tenofovir for prevention of HIV-1 infection in women between Sept 9, 2009, and Aug 13, 2012. Women were assessed monthly for contraceptive use and incident infection. We estimated the difference in incident HIV-1 infection between DMPA and NET-EN users by Cox proportional hazards regression analyses in this prospective cohort. The VOICE trial is registered with ClinicalTrials.gov, NCT00705679.
Findings 3141 South African women using injectable contraception were included in the present analysis: 1788 (56.9%) solely used DMPA, 1097 (34.9%) solely used NET-EN, and 256 (8.2%) used both injectable types at different times during follow-up. During 2733.7 person-years of follow-up, 207 incident HIV-1 infections occurred (incidence 7.57 per 100 person-years, 95% CI 6.61-8.68). Risk of HIV-1 acquisition was higher among DMPA users (incidence 8.62 per 100 person-years, 95% CI 7.35-10.11) than among NET-EN users (5.67 per 100 person-years, 4.35-7.38; hazard ratio 1.53, 95% CI 1.12-2.08; p=0.007). This association persisted when adjusted for potential confounding variables (adjusted hazard ratio [aHR] 1.41, 95% CI 1.06-1.89; p=0.02). Among women seropositive for herpes simplex virus type 2 (HSV-2) at enrolment, the aHR was 2.02 (95% CI 1.26-3.24) compared with 1.09 (0.78-1.52) for HSV-2-seronegative women (p interaction =0.07).
Interpretation Although moderate associations in observational analyses should be interpreted with caution, these findings suggest that NET-EN might be an alternative injectable drug with a lower HIV risk than DMPA in high HIV-1 incidence settings where NET-EN is available.
C1 [Noguchi, Lisa M.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD 21205 USA.
[Richardson, Barbra A.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Baeten, Jared M.] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA.
[Baeten, Jared M.; Marrazzo, Jeanne M.] Univ Washington, Dept Med, Seattle, WA USA.
[Baeten, Jared M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Hillier, Sharon L.; Bunge, Katherine] UPMC, Magee Womens Hosp, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA.
[Hillier, Sharon L.; Bunge, Katherine] Univ Pittsburgh, Pittsburgh, PA USA.
[Balkus, Jennifer E.] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA.
[Chirenje, Z. Mike] UZ UCSF Collaborat Res Programme, Harare, Zimbabwe.
[Ramjee, Gita] South African Med Res Council, HIV Prevent Res Unit, Durban, KwaZulu Natal, South Africa.
[Nair, Gonasagrie] Ctr AIDS Programme Res South Africa, Durban, South Africa.
[Palanee-Phillips, Thesla] Univ Witwatersrand, Fac Hlth Sci, Wits Reprod Hlth & HIV Inst, Johannesburg, South Africa.
[Selepe, Pearl] Aurum Inst, Klerksdorp, South Africa.
[van der Straten, Ariane] RTI Int, Womens Global Hlth Imperat, San Francisco, CA USA.
[Parikh, Urvi M.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA.
[Gomez, Kailazarid] FHI 360, Durham, NC USA.
[Piper, Jeanna M.] NIAID, Div Aids, Bethesda, MD 20892 USA.
[Watts, D. Heather] Dept State, Washington, DC USA.
[Watts, D. Heather] Off Global AIDS Coordinator & Hlth Diplomacy, Washington, DC USA.
RP Noguchi, LM (reprint author), Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD 21205 USA.
EM lnoguch1@jhu.edu
OI Marrazzo, Jeanne/0000-0002-9277-7364
FU National Institutes of Health (NIH); Johns Hopkins Training Program in
Sexually Transmitted Infections [T32-AI050056]; National Institute of
Allergy and Infectious Diseases [UM1AI068633, UM1AI068615, UM1AI106707];
Eunice Kennedy Shriver National Institute of Child Health and Human
Development of the NIH; National Institute of Mental Health of the NIH
FX LMN, BAR, JMB, SLH, JEB, ZMC, KB, GR, GN, TP-P, PS, AvdS, UMP, KG, and
JMM report support from the National Institutes of Health (NIH). LMN
reports support from the Johns Hopkins Training Program in Sexually
Transmitted Infections (T32-AI050056). The Microbicide Trials Network is
funded by the National Institute of Allergy and Infectious Diseases
(UM1AI068633, UM1AI068615, UM1AI106707), with cofunding from the Eunice
Kennedy Shriver National Institute of Child Health and Human Development
and the National Institute of Mental Health, all components of the NIH.
The findings and conclusions in this manuscript are those of the authors
and do not necessarily represent the official views of the NIH, the
Office of the Global AIDS Coordinator, or the US Department of State. We
thank all team members and participants in the VOICE study. LMN
additionally thanks Matthew Reeves, Taha E Taha, and Ron Gray.
NR 40
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U1 3
U2 5
PU ELSEVIER INC
PI SAN DIEGO
PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 2352-3018
J9 LANCET HIV
JI Lancet HIV
PD JUL
PY 2015
VL 2
IS 7
BP E279
EP E287
DI 10.1016/S2352-3018(15)00058-2
PG 9
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA CU8LC
UT WOS:000363793000008
PM 26155597
ER
PT J
AU Meehan, CA
Cochran, E
Mattingly, M
Gorden, P
Brown, RJ
AF Meehan, Cristina Adelia
Cochran, Elaine
Mattingly, Megan
Gorden, Phillip
Brown, Rebecca J.
TI Mild Caloric Restriction Decreases Insulin Requirements in Patients With
Type 2 Diabetes and Severe Insulin Resistance
SO MEDICINE
LA English
DT Article
ID BARIATRIC SURGERY; U-500; GLUCOSE
AB Type 2 diabetes (T2D) affects approximate to 10% of the US population, a subset of whom have severe insulin resistance (SIR) (>200units/d). Treatment of these patients with high-dose insulin presents logistical and compliance challenges. We hypothesized that mild caloric restriction would reduce insulin requirements in patients with T2D and SIR.This was a retrospective study at the National Institutes of Health Clinical Center. Inclusion criteria were as follows: T2D, and insulin dose >200units/d or >2units/kg/d. The intervention consisted of mild caloric restriction during a 3 to 6-day hospitalization. The major outcomes were change in insulin dose and blood glucose from admission to discharge.Ten patients met inclusion criteria. Baseline glycated hemoglobin A(1c) was 10.01.6% and body mass index 38.8 +/- 9.0kg/m(2). Food intake was restricted from 2210 +/- 371kcal/d preadmission to 1810 +/- 202 during the hospital stay (16.5% reduction). Insulin dose decreased from 486 +/- 291units/d preadmission to 223 +/- 127 at discharge (44% reduction, P=0.0025). Blood sugars decreased nonsignificantly in the fasting state (from 184 +/- 85 to 141 +/- 42, P=0.20), before lunch (239 +/- 68 to 180 +/- 76, P=0.057), and at bedtime (212 +/- 95 to 176 +/- 48, P=0.19), and significantly decreased before dinner (222 +/- 92 to 162 +/- 70, P=0.016).Mild caloric restriction, an accessible and affordable intervention, substantially reduced insulin doses in patients with T2D and SIR. Further studies are needed to determine if the intervention and results are sustainable outside of a hospital setting.
C1 [Meehan, Cristina Adelia; Cochran, Elaine; Mattingly, Megan; Gorden, Phillip; Brown, Rebecca J.] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA.
RP Gorden, P (reprint author), NIDDK, Diabet Endocrinol & Obes Branch, NIH, 10-CRC Room 6-5952,MSC 1612,10 Ctr Dr, Bethesda, MD 20892 USA.
EM gordenp@extra.niddk.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases
FX This work was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases.
NR 12
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U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0025-7974
EI 1536-5964
J9 MEDICINE
JI Medicine (Baltimore)
PD JUL
PY 2015
VL 94
IS 30
AR e1160
DI 10.1097/MD.0000000000001160
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA CU6KJ
UT WOS:000363640600001
PM 26222846
ER
PT J
AU Ferris, RL
Baloch, Z
Bernet, V
Chen, A
Fahey, TJ
Ganly, I
Hodak, SP
Kebebew, E
Patel, KN
Shaha, A
Steward, DL
Tufano, RP
Wiseman, SM
Carty, SE
AF Ferris, Robert L.
Baloch, Zubair
Bernet, Victor
Chen, Amy
Fahey, Thomas J.
Ganly, Ian
Hodak, Steven P.
Kebebew, Electron
Patel, Kepal N.
Shaha, Ashok
Steward, David L.
Tufano, Ralph P.
Wiseman, Sam M.
Carty, Sally E.
TI American Thyroid Association Statement on Surgical Application of
Molecular Profiling for Thyroid Nodules: Current Impact on Perioperative
Decision Making
SO THYROID
LA English
DT Article
ID FINE-NEEDLE-ASPIRATION; GENE-EXPRESSION CLASSIFIER; BRAF V600E MUTATION;
UNDETERMINED SIGNIFICANCE; GENOMIC CHARACTERIZATION; BETHESDA SYSTEM;
FNA SPECIMENS; DIAGNOSIS; CANCER; CYTOLOGY
AB Background: Recent advances in research on thyroid carcinogenesis have yielded applications of diagnostic molecular biomarkers and profiling panels in the management of thyroid nodules. The specific utility of these novel, clinically available molecular tests is becoming widely appreciated, especially in perioperative decision making by the surgeon regarding the need for surgery and the extent of initial resection. Methods: A task force was convened by the Surgical Affairs Committee of the American Thyroid Association and was charged with writing this article. Results/Conclusions: This review covers the clinical scenarios by cytologic category for which the thyroid surgeon may find molecular profiling results useful, particularly for cases with indeterminate fine-needle aspiration cytology. Distinct strengths of each ancillary test are highlighted to convey the current status of this evolving field, which has already demonstrated the potential to streamline decision making and reduce unnecessary surgery, with the accompanying benefits. However, the performance of any diagnostic test, that is, its positive predictive value and negative predictive value, are exquisitely influenced by the prevalence of cancer in that cytologic category, which is known to vary widely at different medical centers. Thus, it is crucial for the clinician to know the prevalence of malignancy within each indeterminate cytologic category, at one's own institution. Without this information, the performance of the diagnostic tests discussed below may vary substantially.
C1 [Ferris, Robert L.] Univ Pittsburgh, Inst Canc, Dept Otolaryngol, Div Head & Neck Surg, Pittsburgh, PA 15213 USA.
[Baloch, Zubair] Univ Penn, Dept Pathol, Med Ctr, Philadelphia, PA 19104 USA.
[Bernet, Victor] Mayo Clin, Dept Endocrinol, Jacksonville, FL 32224 USA.
[Chen, Amy] Emory Univ, Dept Otolaryngol Head & Neck Surg, Atlanta, GA 30322 USA.
[Fahey, Thomas J.] New York Presbyterian Hosp, Dept Surg, New York, NY USA.
[Ganly, Ian; Shaha, Ashok] Mem Sloan Kettering Canc Ctr, Head & Neck Serv, New York, NY 10021 USA.
[Hodak, Steven P.] NYU, Med Ctr, Div Endocrinol, New York, NY 10016 USA.
[Patel, Kepal N.] NYU, Med Ctr, Div Endocrine Surg, New York, NY 10016 USA.
[Kebebew, Electron] NCI, Endocrine Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Steward, David L.] Univ Cincinnati, Med Ctr, Dept Otolaryngol Head & Neck Surg, Cincinnati, OH 45267 USA.
[Tufano, Ralph P.] Johns Hopkins Univ, Dept Otolaryngol Head & Neck Surg, Baltimore, MD USA.
[Wiseman, Sam M.] St Pauls Hosp, Dept Surg, Div Gen Surg, Vancouver, BC V6Z 1Y6, Canada.
[Wiseman, Sam M.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
[Carty, Sally E.] Univ Pittsburgh, Med Ctr, Dept Surg, Div Endocrine Surg, Pittsburgh, PA 15213 USA.
RP Ferris, RL (reprint author), Univ Pittsburgh, Inst Canc, 200 Lothrop St,Suite 500, Pittsburgh, PA 15213 USA.
EM ferrisrl@upmc.edu
OI Ganly, Ian/0000-0001-7636-5426; patel, kepal/0000-0002-9088-4844
FU Veracyte
FX Dr. Fahey reports a patent that has been licensed to Prolias Inc. and
serves on the Scientific Advisory Board of Prolias Inc. Dr. Steward
declares research grant funding (clinical trial) from Veracyte. No
competing financial interests exist for the remaining authors.
NR 51
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Z9 35
U1 0
U2 5
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1050-7256
EI 1557-9077
J9 THYROID
JI Thyroid
PD JUL 1
PY 2015
VL 25
IS 7
BP 760
EP 768
DI 10.1089/thy.2014.0502
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CU9TB
UT WOS:000363887000003
PM 26058403
ER
PT J
AU Bigman, G
Rajesh, V
Koehly, LM
Strong, LL
Oluyomi, AO
Strom, SS
Wilkinson, AV
AF Bigman, Galya
Rajesh, Vandita
Koehly, Laura M.
Strong, Larkin L.
Oluyomi, Abiodun O.
Strom, Sara S.
Wilkinson, Anna V.
TI Family Cohesion and Moderate-to-Vigorous Physical Activity Among Mexican
Origin Adolescents: A Longitudinal Perspective
SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH
LA English
DT Article
DE youth; cohort; active behavior; family interactions
ID CROSS-SECTIONAL ANALYSIS; MIDDLE SCHOOL STUDENTS; SENSATION-SEEKING;
SUBSTANCE USE; DEVIANT-BEHAVIOR; SOCIAL SUPPORT; YOUTH; ACCULTURATION;
CHILDHOOD; ANXIETY
AB Background: Existing racial/ethnic disparities in physical activity during childhood increase Hispanics' risk of developing chronic diseases, which serves to increase health disparities. This study examined associations of family cohesion and conflict with self-reported moderate-to-vigorous physical activity (MVPA), controlling for psychosocial covariates such as subjective social status, anxiety, and sensation-seeking. Methods: 1000 Mexican origin adolescents reported their MVPA levels approximately 2 years apart. Psychosocial covariates, family cohesion and conflict were measured at the first assessment. Generalized Linear Models were used to prospectively examine the relationship between family cohesion and conflict and subsequent MVPA based on 711 participants who had low levels of baseline MVPA. Results: 35% of boys and 24% of girls reported adequate MVPA levels at follow-up; girls were less likely to report adequate MVPA (RR = 0.76; 95% CI: 0.61-0.93) than boys. Overall, family cohesion was associated with MVPA (P = .01), but family cohesion was not (P = .41). Gender-based analyses revealed that adequate MVPA was associated with family cohesion (RR = 1.40; 95% CI: 1.03-1.88), sensation seeking (RR = 1.05; 95% CI: 1.00-1.10), and age (RR = 0.85; 95% CI: 0.74-0.98) among girls and with subjective social status (RR = 1.20; 95% CI: 1.08-1.33) among boys. Conclusions: The family social environment and gender differences should be addressed in health promotion programs targeting MVPA.
C1 [Bigman, Galya; Rajesh, Vandita] Univ Texas Sch Publ Hlth, Dept Epidemiol Human Genet & Environm Sci, Austin, TX 77030 USA.
[Koehly, Laura M.] NIH, Intramural Res Program, Bethesda, MD 20892 USA.
[Strong, Larkin L.] Univ Texas MD Anderson Canc Ctr, Dept Hlth Dispar Res, Houston, TX 77030 USA.
[Oluyomi, Abiodun O.; Wilkinson, Anna V.] Univ Texas Sch Publ Hlth, Michael & Susan Dell Ctr Hlth Living, Austin, TX USA.
RP Bigman, G (reprint author), Univ Texas Sch Publ Hlth, Dept Epidemiol Human Genet & Environm Sci, Austin, TX 77030 USA.
EM galya.bigman@uth.tmc.edu
FU National Cancer Institute [CA 126988]; National Human Genome Research
Institute at the National Institutes of Health [Z01HG200335]; Caroline
W. Law Fund for Cancer Prevention; Dan Duncan Family Institute for Risk
Assessment and Cancer Prevention
FX We thank the field staff for their on-going work with participant
recruitment and follow-up. Most importantly, we thank our study
participants and their parents for their cooperation and participation,
without which this research would not be possible. This research is
supported by the National Cancer Institute grants [CA 126988 to AVW] and
partially supported by the Intramural Research Program of the National
Human Genome Research Institute at the National Institutes of Health
[Z01HG200335-LMK]. The Mexican American Cohort receives funds collected
pursuant to the Comprehensive Tobacco Settlement of 1998 and
appropriated by the 76th legislature to The University of Texas M. D.
Anderson Cancer Center; from the Caroline W. Law Fund for Cancer
Prevention, and the Dan Duncan Family Institute for Risk Assessment and
Cancer Prevention. The funders did not contribute to the design and
conduct of the study, the data collection, analysis, and interpretation
of the data, the preparation, review, or approval of the manuscript.
NR 56
TC 1
Z9 1
U1 1
U2 5
PU HUMAN KINETICS PUBL INC
PI CHAMPAIGN
PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA
SN 1543-3080
EI 1543-5474
J9 J PHYS ACT HEALTH
JI J. Phys. Act. Health
PD JUL
PY 2015
VL 12
IS 7
BP 1023
EP 1030
DI 10.1123/jpah.2014-0014
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CU2NN
UT WOS:000363360300019
PM 25919963
ER
PT J
AU Korkmaz, S
Karadag, MA
Hamamcioglu, K
Sofikerim, M
Aksu, M
AF Korkmaz, Selda
Karadag, Mert Ali
Hamamcioglu, Kemal
Sofikerim, Mustafa
Aksu, Murat
TI Electrophysiological Identification of Central Sensitization in Patients
with Chronic Prostatitis
SO UROLOGY JOURNAL
LA English
DT Article
DE chronic pain; physiopathology; evoked potentials; somatosensory;
neuropsychological tests; prostatitis; physiopathology
ID PELVIC PAIN SYNDROME; TREATMENT RESPONSE; MEN; FEATURES
AB Purpose: Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a chronic pain condition and a common problem in urology clinics. Although many different etiologies and mechanisms exist, the exact cause of the disease has been unknown. Central sensitization (CS) is defined as an augmentation of responsiveness of central cortical neurons to input from peripheral nociceptive structures. Somatosensory evoked potentials (SEPs) is an electroneurophysiological method to assess cortical activity in somatosensory area of brain related to sensorial stimuli. We aimed to determine the presence of CS using the SEPs of dorsal penile nerve stimulation in patients with CP/CPPS.
Materials and Methods: Seventeen male patients diagnosed CP/CPPS and 17 male healthy controls were prospectively included in the study. For SEP study, electrical stimulus was applied with penile ring electrodes. Recording electrodes were placed as active to Cz' and reference electrode on Fz' according to the 10-20 International System. Latency of N50 was defined as the second negative (upward) deflection of the W-shaped averaged cortical waveform.
Results: N50 latencies were significantly shortened in the patient group compared to the healthy controls (P < .001).
Conclusion: These results support the presence of central sensitization because of exaggerated transmission of pain sensation to the somatosensory cortex. Therefore, normalization of transmission might be an important step in treatment of pain in patients with CP/CPPS. This study can be counted as an important guiding on pathogenesis and treatment of disease.
C1 [Korkmaz, Selda] NINDS, NIH, Human Motor Control Sect, Bethesda, MD 20892 USA.
[Karadag, Mert Ali] Kafkas Univ, Dept Urol, Coll Med, Kars, Turkey.
[Hamamcioglu, Kemal] Acibadem Kayseri Hosp, Dept Neurol, Kayseri, Turkey.
[Sofikerim, Mustafa] Acibadem Univ, Coll Med, Acibadem Kayseri Hosp, Dept Urol, Istanbul, Turkey.
[Aksu, Murat] Acibadem Univ, Coll Med, Acibadem Kayseri Hosp, Dept Neurol, Istanbul, Turkey.
RP Korkmaz, S (reprint author), NINDS, NIH, Human Motor Control Sect, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM korkmazs78@gmail.com
RI Sofikerim, Mustafa/D-6985-2016
NR 18
TC 2
Z9 3
U1 0
U2 0
PU UROL & NEPHROL RES CTR-UNRC
PI TEHRAN
PA NO 44, 9TH BOUSTAN ST, PASADARAN AVE, TEHRAN, 00000, IRAN
SN 1735-1308
EI 1735-546X
J9 UROL J
JI Urol. J.
PD JUL-AUG
PY 2015
VL 12
IS 4
BP 2280
EP 2284
PG 5
WC Urology & Nephrology
SC Urology & Nephrology
GA CU0RJ
UT WOS:000363226100014
PM 26341773
ER
PT J
AU Matyugina, ES
Novikov, MS
Babkov, DA
Valuev-Elliston, VT
Vanpouille, C
Zicari, S
Corona, A
Tramontano, E
Margolis, LB
Khandazhinskaya, AL
Kochetkov, SN
AF Matyugina, E. S.
Novikov, M. S.
Babkov, D. A.
Valuev-Elliston, V. T.
Vanpouille, C.
Zicari, S.
Corona, A.
Tramontano, E.
Margolis, L. B.
Khandazhinskaya, A. L.
Kochetkov, S. N.
TI 5-Arylaminouracil Derivatives as Potential Dual-Action Agents
SO ACTA NATURAE
LA English
DT Article
DE 5-(phenylamino) uracil derivatives; 5 '-norcarbocyclic nucleoside
analogs; HIV and Mycobacterium tuberculosis co-infection; dual action
ID HIV-1 REVERSE-TRANSCRIPTASE; NONNUCLEOSIDE INHIBITORS
AB Several 5-aminouracil derivatives that have previously been shown to inhibit Mycobacterium tuberculosis growth at concentrations of 5-40 mu g/mL are demonstrated to act also as noncompetitive non-nucleoside inhibitors of HIV-1 reverse transcriptase without causing toxicity in vitro (MT-4 cells) and ex vivo (human tonsillar tissue).
C1 [Matyugina, E. S.; Valuev-Elliston, V. T.; Khandazhinskaya, A. L.; Kochetkov, S. N.] Engelhardt Inst Mol Biol, Moscow 119991, Russia.
[Novikov, M. S.; Babkov, D. A.] Volgograd State Med Univ, Dept Pharmaceut & Toxicol Chem, Volgograd 400131, Russia.
[Vanpouille, C.; Zicari, S.; Margolis, L. B.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
[Corona, A.; Tramontano, E.] Univ Cagliari, Dept Life & Environm Sci, I-09042 Monserrato, Italy.
RP Margolis, LB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
EM margolil@helix.nih.gov; khandazhinskaya@bk.ru
RI Valuev-Elliston, Vladimir/I-3067-2014; Matyugina, Elena/Q-4345-2016;
Babkov, Denis/B-6502-2017
OI Valuev-Elliston, Vladimir/0000-0003-0365-570X; Babkov,
Denis/0000-0002-9645-3324
FU Intramural Program of the National Institute of Child Health and Human
Development, National Institutes of Health (NIH, USA) [13-04-91441];
Russian Foundation for Basic Research; Russian Foundation for Basic
Research [13-04-00742]
FX This work was supported by joint project No 13-04-91441 of the
Intramural Program of the National Institute of Child Health and Human
Development, National Institutes of Health (NIH, USA) and the Russian
Foundation for Basic Research, as well as by a project of the Russian
Foundation for Basic Research No 13-04-00742.
NR 10
TC 0
Z9 0
U1 0
U2 1
PU RUSSIAN FEDERATION AGENCY SCIENCE & INNOVATION
PI MOSCOW
PA NAUCHNY PARK MGU, VLAD 1, STROENIYE 75G, LENINSKIYE GORY, MOSCOW,
119991, RUSSIA
SN 2075-8251
J9 ACTA NATURAE
JI Acta Naturae
PD JUL-SEP
PY 2015
VL 7
IS 3
BP 113
EP 115
PG 3
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CT5YT
UT WOS:000362887900014
PM 26483967
ER
PT J
AU Fee, E
Brown, TM
Manuelpillai, W
AF Fee, Elizabeth
Brown, Theodore M.
Manuelpillai, Wesline
TI Mervyn Susser (1921-2014): Fighter for Social Justice and Pioneer in
Epidemiology
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Editorial Material
C1 [Fee, Elizabeth] Natl Lib Med, NIH, Bethesda, MD 20894 USA.
[Brown, Theodore M.; Manuelpillai, Wesline] Univ Rochester, Rochester, NY USA.
RP Fee, E (reprint author), Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA.
EM feee@mail.nih.gov
NR 6
TC 0
Z9 0
U1 0
U2 2
PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
EI 1541-0048
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD JUL
PY 2015
VL 105
IS 7
BP 1316
EP 1316
DI 10.2105/AJPH.2015.302633
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CT6FX
UT WOS:000362909400013
PM 25973815
ER
PT J
AU Paksarian, D
Rudolph, KE
He, JP
Merikangas, KR
AF Paksarian, Diana
Rudolph, Kara E.
He, Jian-Ping
Merikangas, Kathleen R.
TI School Start Time and Adolescent Sleep Patterns: Results From the US
National Comorbidity Survey-Adolescent Supplement
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Article
ID CATCH-UP SLEEP; NCS-A; REPRESENTATIVE SAMPLE; KOREAN ADOLESCENTS;
DURATION; ASSOCIATION; AGE; SEX; PERFORMANCE; TEENAGERS
AB Objectives. We estimated associations between school start time and adolescent weeknight bedtime, weeknight sleep duration, and weekend compensatory sleep and assessed whether associations differ by age, sex, or urbanicity.
Methods. We used a subsample of a nationally representative, cross-sectional survey of 7308 students aged 13 to 18 years attending 245 schools to estimate associations of school start time, reported by school principals, with weeknight bedtime and sleep duration and weekend compensatory sleep, reported during adolescent face-to-face interviews.
Results. Start time was positively associated with weeknight bedtime. Associations between start time and weeknight sleep duration were nonlinear and were strongest for start times of 8: 00 AM and earlier. Associations differed by sex and urbanicity, with the strongest association among boys in major metropolitan counties. Start time was negatively associated with sleep duration among boys in nonurban counties. Start time was not associated with weekend compensatory sleep.
Conclusions. Positive overall associations between school start time and adolescent sleep duration at the national level support recent policy recommendations for delaying school start times. However, the impact of start time delays may differ by sex and urbanicity.
C1 [Paksarian, Diana; He, Jian-Ping; Merikangas, Kathleen R.] NIMH, Genet Epidemiol Res Branch, Bethesda, MD 20892 USA.
[Rudolph, Kara E.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA.
[Rudolph, Kara E.] Univ Calif San Francisco, Ctr Hlth & Community, San Francisco, CA 94143 USA.
RP Merikangas, KR (reprint author), NIMH, 35A Convent Dr,MSC 3720, Bethesda, MD 20892 USA.
EM kathleen.merikangas@nih.gov
FU National Institute of Mental Health; National Institute of Mental Health
[ZIA-MH002808, U01-MH60220]
FX This study was supported by the Intramural Research Program, National
Institute of Mental Health. The National Comorbidity Survey-Adolescent
Supplement is supported by the National Institute of Mental Health
(ZIA-MH002808 and U01-MH60220).
NR 47
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Z9 6
U1 5
U2 12
PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
EI 1541-0048
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD JUL
PY 2015
VL 105
IS 7
BP 1351
EP 1357
DI 10.2105/AJPH.2015.302619
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CT6FX
UT WOS:000362909400019
PM 25973803
ER
PT J
AU Eaton, NR
Thompson, RG
Hu, MC
Goldstein, RB
Saha, TD
Hasin, DS
AF Eaton, Nicholas R.
Thompson, Ronald G., Jr.
Hu, Mei-Chen
Goldstein, Rise B.
Saha, Tulshi D.
Hasin, Deborah S.
TI Regularly Drinking Alcohol Before Sexual Activity in a Nationally
Representative Sample: Prevalence, Sociodemographics, and Associations
With Psychiatric and Substance Use Disorders
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; GENERAL-POPULATION SAMPLE; UNPROTECTED
SEX; RISKY SEX; SENSATION SEEKING; CONDOM USE; BEHAVIOR; MEN;
ADOLESCENTS; INTERVENTIONS
AB Objectives. We addressed regular drinking before sex and its associated risk factors.
Methods. From the wave 2 National Epidemiologic Survey on Alcohol and Related Conditions, a nationally representative adult US sample (fielded 20042005), we determined the 12-month prevalence of regularly drinking alcohol before sexual activity. Among 17 491 sexually active drinkers, we determined the sociodemographic, psychiatric, and substance use correlates of regularly drinking before sex.
Results. Regular presex drinking's 12-month prevalence was 1.8%. Significant bivariate sociodemographic correlates were age, gender, race/ethnicity, education, family income, marital status, and employment status. Generalized anxiety disorder and alcohol dependence were associated with significantly increased odds of being a regular presex drinker after controlling for covariates.
Conclusions. We estimate that 4.3 million American adults are regular presex drinkers. Future research should examine this public health issue at the population level, with particular focus on pathways that link it to psychopathology.
C1 [Eaton, Nicholas R.] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA.
[Thompson, Ronald G., Jr.; Hu, Mei-Chen; Hasin, Deborah S.] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA.
[Goldstein, Rise B.; Saha, Tulshi D.] NIAAA, NIH, Bethesda, MD USA.
RP Eaton, NR (reprint author), SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA.
EM nicholas.eaton@stonybrook.edu
OI Goldstein, Rise/0000-0002-9603-9473
FU National Institute on Alcohol Abuse and Alcoholism (NIAAA); National
Institute on Drug Abuse; National Institutes of Health, NIAAA; National
Institute on Drug Abuse [K23DA032323]; NIAAA [U01AA018111]; New York
State Psychiatric Institute
FX The National Epidemiologic Survey on Alcohol and Related Conditions was
funded by the National Institute on Alcohol Abuse and Alcoholism (NIAAA)
with supplemental support from the National Institute on Drug Abuse.
This research was supported in part by the Intramural Program of the
National Institutes of Health, NIAAA (to R. B. G. and T. D. S.), the
National Institute on Drug Abuse (grant K23DA032323 to R. G. T.), NIAAA
(grant U01AA018111 to D. S. H.), and the New York State Psychiatric
Institute (to D. S. H.).
NR 39
TC 5
Z9 5
U1 3
U2 4
PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
EI 1541-0048
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD JUL
PY 2015
VL 105
IS 7
BP 1387
EP 1393
DI 10.2105/AJPH.2015.302556
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CT6FX
UT WOS:000362909400024
PM 25973812
ER
PT J
AU Kim, YJ
Guzman-Hernandez, ML
Wisniewski, E
Balla, T
AF Kim, Y. J.
Guzman-Hernandez, M. L.
Wisniewski, E.
Balla, T.
TI Phosphoinositide turnover and lipid transport. A marriage born at
membrane contact sites
SO FEBS JOURNAL
LA English
DT Meeting Abstract
CT 40th Congress of the Federation-of-European-Biochemical-Societies (FEBS)
- The Biochemical Basis of Life
CY JUL 04-09, 2015
CL Berlin, GERMANY
SP Federat European Biochemical Soc
C1 [Kim, Y. J.; Guzman-Hernandez, M. L.; Wisniewski, E.; Balla, T.] NICHD, NIH, Bethesda, MD USA.
RI Wisniewski, Eva/O-9233-2015
OI Wisniewski, Eva/0000-0001-8698-6867
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 1742-464X
EI 1742-4658
J9 FEBS J
JI FEBS J.
PD JUL
PY 2015
VL 282
SU 1
SI SI
BP 44
EP 44
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CT1PC
UT WOS:000362570600122
ER
PT J
AU Chang, YSN
Yeh, HL
Siu, MK
Yin, JJ
Chen, WYN
Liu, YN
AF Chang, Y. -S. N.
Yeh, H. -L.
Siu, M. K.
Yin, J. J.
Chen, W. -Y. N.
Liu, Y. -N.
TI Epidermal growth factor receptor promotes prostate cancer bone
metastasis through down-regulation of miR-1 and activation of TWIST1
SO FEBS JOURNAL
LA English
DT Meeting Abstract
CT 40th Congress of the Federation-of-European-Biochemical-Societies (FEBS)
- The Biochemical Basis of Life
CY JUL 04-09, 2015
CL Berlin, GERMANY
SP Federat European Biochemical Soc
C1 [Chang, Y. -S. N.; Liu, Y. -N.] Taipei Med Univ, Grad Inst Canc Biol & Drug Discovery, Taipei, Taiwan.
[Yeh, H. -L.] Natl Tsing Hua Univ, Inst Informat Syst & Applicat, Hsinchu, Taiwan.
[Siu, M. K.] Taipei Med Univ, PhD Program Canc Biol & Drug Discovery, Taipei, Taiwan.
[Siu, M. K.] Wan Fang Hosp, Dept Anesthesiol, Taipei, Taiwan.
[Yin, J. J.] NCI, NIH, Cell & Canc Biol Branch, Bethesda, MD 20892 USA.
[Chen, W. -Y. N.] Taipei Med Univ, Taipei, Taiwan.
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 1742-464X
EI 1742-4658
J9 FEBS J
JI FEBS J.
PD JUL
PY 2015
VL 282
SU 1
SI SI
MA P03-015
BP 73
EP 73
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CT1PC
UT WOS:000362570601061
ER
PT J
AU Fricke, T
Valle-Casuso, JC
Bhattacharya, A
White, TE
Nez, ABN
Buffone, C
Opp, S
Reszka, N
Bosche, WJ
Gorelick, R
Alam, SL
Zadrozny, K
Sedzicki, J
Taylor, AB
Demeler, B
Pornillos, O
Ganser-Pornillos, BK
Ivanov, DN
Yeager, M
Diaz-Griffero, F
AF Fricke, T.
Valle-Casuso, J. C.
Bhattacharya, A.
White, T. E.
Nez, A. Brandariz-Nu
Buffone, C.
Opp, S.
Reszka, N.
Bosche, W. J.
Gorelick, R.
Alam, S. L.
Zadrozny, K.
Sedzicki, J.
Taylor, A. B.
Demeler, B.
Pornillos, O.
Ganser-Pornillos, B. K.
Ivanov, D. N.
Yeager, M.
Diaz-Griffero, F.
TI Characterizing the role of CPSF6 in HIV-1 infection by using
small-molecule inhibitors
SO FEBS JOURNAL
LA English
DT Meeting Abstract
CT 40th Congress of the Federation-of-European-Biochemical-Societies (FEBS)
- The Biochemical Basis of Life
CY JUL 04-09, 2015
CL Berlin, GERMANY
SP Federat European Biochemical Soc
C1 [Fricke, T.; Valle-Casuso, J. C.; White, T. E.; Nez, A. Brandariz-Nu; Buffone, C.; Opp, S.; Reszka, N.; Diaz-Griffero, F.] Albert Einstein Coll Med, Dept Microbiol & Immunol, New York, NY USA.
[Fricke, T.] Int Inst Mol & Cell Biol, Struct Biol Lab, Warsaw, Poland.
[Bhattacharya, A.; Taylor, A. B.; Demeler, B.; Ivanov, D. N.] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem & Canc Therapy, San Antonio, TX 78229 USA.
[Bhattacharya, A.; Taylor, A. B.; Demeler, B.; Ivanov, D. N.] Univ Texas Hlth Sci Ctr San Antonio, Res Ctr, San Antonio, TX 78229 USA.
[Bosche, W. J.; Gorelick, R.] SAIC Frederick, AIDS & Canc Virus Program, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Alam, S. L.] Univ Utah, Dept Biochem, Salt Lake City, UT USA.
[Zadrozny, K.; Sedzicki, J.; Pornillos, O.; Ganser-Pornillos, B. K.; Yeager, M.] Univ Virginia, Sch Med, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA.
[Pornillos, O.; Yeager, M.] Univ Virginia, Sch Med, Ctr Membrane Biol, Charlottesville, VA 22908 USA.
[Yeager, M.] Univ Virginia, Sch Med, Cardiovasc Res Ctr, Charlottesville, VA 22908 USA.
[Yeager, M.] Univ Virginia, Sch Med, Div Cardiovasc Med, Charlottesville, VA 22908 USA.
NR 5
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1742-464X
EI 1742-4658
J9 FEBS J
JI FEBS J.
PD JUL
PY 2015
VL 282
SU 1
SI SI
MA P14-009
BP 130
EP 130
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CT1PC
UT WOS:000362570602089
ER
PT J
AU Tuna, G
Islekel, GH
Ozkaya, F
Yener, GG
Kirkali, FG
AF Tuna, G.
Islekel, G. H.
Ozkaya, F.
Yener, G. G.
Kirkali, F. G.
TI Plasma levels of matrix metalloproteinases-2,-9 and tissue inhibitors of
metalloproteinases-1,-2 in Alzheimer's disease
SO FEBS JOURNAL
LA English
DT Meeting Abstract
CT 40th Congress of the Federation-of-European-Biochemical-Societies (FEBS)
- The Biochemical Basis of Life
CY JUL 04-09, 2015
CL Berlin, GERMANY
SP Federat European Biochemical Soc
DE Alzheimer's disease; matrix metalloproteinases; tissue inhibitor of
metalloproteinases; ELISA
C1 [Tuna, G.; Islekel, G. H.] Dokuz Eylul Univ, Sch Med, Dept Med Biochem, Izmir, Turkey.
[Ozkaya, F.] Dokuz Eylul Univ, Sch Med, Dept Mol Med, Izmir, Turkey.
[Yener, G. G.] Dokuz Eylul Univ, Sch Med, Dept Neurol, Izmir, Turkey.
[Yener, G. G.] Istanbul Kultur Univ, Brain Dynam Cognit & Complex Syst Res Ctr, Istanbul, Turkey.
[Kirkali, F. G.] NCI, Dev Therapeut Branch, Mol Pharmacol Grp, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1742-464X
EI 1742-4658
J9 FEBS J
JI FEBS J.
PD JUL
PY 2015
VL 282
SU 1
SI SI
MA P22-021
BP 177
EP 177
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CT1PC
UT WOS:000362570603059
ER
PT J
AU Pasqualini, L
Bu, H
Puhr, M
Narisu, N
Rainer, J
Schlick, B
Schafer, F
Angelova, M
Trajanoski, Z
Schweiger, MR
Fuchsberger, C
Klocker, H
AF Pasqualini, L.
Bu, H.
Puhr, M.
Narisu, N.
Rainer, J.
Schlick, B.
Schaefer, F.
Angelova, M.
Trajanoski, Z.
Schweiger, M. R.
Fuchsberger, C.
Klocker, H.
TI microRNAs as effectors regulated by androgen receptor in prostate cancer
SO FEBS JOURNAL
LA English
DT Meeting Abstract
CT 40th Congress of the Federation-of-European-Biochemical-Societies (FEBS)
- The Biochemical Basis of Life
CY JUL 04-09, 2015
CL Berlin, GERMANY
SP Federat European Biochemical Soc
C1 [Pasqualini, L.; Puhr, M.; Schlick, B.; Klocker, H.] Med Univ Innsbruck, Urol, A-6020 Innsbruck, Austria.
[Bu, H.] Univ Innsbruck, A-6020 Innsbruck, Austria.
[Narisu, N.] NIH, Bethesda, MD 20892 USA.
[Rainer, J.; Angelova, M.; Trajanoski, Z.] Bioctr Innsbruck, Innsbruck, Austria.
[Schaefer, F.] Med Univ Innsbruck, Pathol, A-6020 Innsbruck, Austria.
[Schweiger, M. R.] Max Planck Inst Mol Genet, D-14195 Berlin, Germany.
[Fuchsberger, C.] Univ Michigan, Ann Arbor, MI 48109 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 1742-464X
EI 1742-4658
J9 FEBS J
JI FEBS J.
PD JUL
PY 2015
VL 282
SU 1
SI SI
MA P06-008-SP
BP 216
EP 216
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CT1PC
UT WOS:000362570604013
ER
PT J
AU Nachman, RM
Fox, SD
Golden, WC
Sibinga, E
Groopman, JD
Lees, PSJ
AF Nachman, Rebecca M.
Fox, Stephen D.
Golden, W. Christopher
Sibinga, Erica
Groopman, John D.
Lees, Peter S. J.
TI Serial Free Bisphenol A and Bisphenol A Glucuronide Concentrations in
Neonates
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID TANDEM MASS-SPECTROMETRY; BREAST-MILK; EXPOSURE; URINE; CHILDREN;
ASSOCIATION; CHEMICALS
AB Objective To determine the balance of metabolism of free bisphenol A (BPA) to the inactive conjugate, BPA glucuronide (BPAG), in neonates.
Study design Free BPA and BPAG concentrations were measured in 78 urine samples collected between December 2012 and August 2013 from a cohort of 44 healthy full term (>= 37 weeks' gestation) neonates at 2 intervals (3-6 days and 7-27 days of age). A questionnaire was administered at the time of sample collection. Neonates recruited into the study were born in an urban, tertiary care hospital.
Results Only BPAG was detected in the urine samples; concentrations ranged from <0.1 mu g/L to 11.21 mu g/L (median: 0.27 mu g/L). Free BPA concentrations were below the limit of quantification of 0.1 mu g/L. Age, but not sex or type of diet, was significantly associated with urinary BPAG concentration (P = .002).
Conclusions Our results illustrate widespread BPA exposure in healthy full-term neonates and efficient conjugation of BPA to its readily excretable and biologically inactive form (BPAG) as early as 3 days of age. Factors other than type of diet may be important contributors to BPA exposure in neonates.
C1 [Nachman, Rebecca M.; Groopman, John D.; Lees, Peter S. J.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA.
[Fox, Stephen D.] Leidos Biomed Res Inc, Canc Res Technol Program, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Golden, W. Christopher] Johns Hopkins Univ, Sch Med, Dept Pediat, Eudowood Neonatal Pulm Div, Baltimore, MD 21205 USA.
[Sibinga, Erica] Johns Hopkins Univ, Sch Med, Dept Pediat, Div Gen Pediat & Adolescent Med, Baltimore, MD 21205 USA.
RP Nachman, RM (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA.
FU Johns Hopkins Center for a Livable Future Lerner Fellowship; Wendy Klag
Memorial Fund; National Institutes of Health [P01 ES006052, P30
ES003819, P30 CA006973, N01-CO-12400, T32 ES007141]
FX Supported by the Johns Hopkins Center for a Livable Future Lerner
Fellowship, the Wendy Klag Memorial Fund, and the National Institutes of
Health (P01 ES006052, P30 ES003819, P30 CA006973, N01-CO-12400, and T32
ES007141). 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 United States Government. The authors declare
no conflicts of interest.
NR 44
TC 2
Z9 2
U1 1
U2 7
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 JUL
PY 2015
VL 167
IS 1
BP 64
EP 69
DI 10.1016/j.jpeds.2015.03.036
PG 6
WC Pediatrics
SC Pediatrics
GA CS9ZS
UT WOS:000362453900017
PM 25921439
ER
PT J
AU Romero, F
Shah, D
Duong, M
Penn, RB
Fessler, MB
Madenspacher, J
Stafstrom, W
Kavuru, M
Lu, B
Kallen, CB
Walsh, K
Summer, R
AF Romero, Freddy
Shah, Dilip
Duong, Michelle
Penn, Raymond B.
Fessler, Michael B.
Madenspacher, Jennifer
Stafstrom, William
Kavuru, Mani
Lu, Bo
Kallen, Caleb B.
Walsh, Kenneth
Summer, Ross
TI A Pneumocyte-Macrophage Paracrine Lipid Axis Drives the Lung toward
Fibrosis
SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
LA English
DT Article
DE pulmonary fibrosis; foam cells; alveolar macrophages; type II
pneumocytes; oxidized phospholipids
ID GROWTH-FACTOR-BETA; BRONCHOALVEOLAR LAVAGE FLUID; INDUCED
PULMONARY-FIBROSIS; CSF-DEFICIENT MICE; GM-CSF; ALVEOLAR MACROPHAGES;
SURFACTANT LIPIDS; OXIDATIVE STRESS; PROTEIN-KINASE; IN-VITRO
AB Lipid-laden macrophages, or "foam cells," are observed in the lungs of patients with fibrotic lung disease, but their contribution to disease pathogenesis remains unexplored. Here, we demonstrate that fibrosis induced by bleomycin, silica dust, or thoracic radiation promotes early and sustained accumulation of foam cells in the lung. In the bleomycin model, we show that foam cells arise from neighboring alveolar epithelial type II cells, which respond to injury by dumping lipids into the distal airspaces of the lungs. We demonstrate that oxidized phospholipids accumulate within alveolar macrophages (AMs) after bleomycin injury and that murine and human AMs treated with oxidized phosphatidylcholine (oxPc) become polarized along an M2 phenotype and display enhanced production of transforming growth factor-beta 1. The direct instillation of oxPc into the mouse lung induces foam cell formation and triggers a severe fibrotic reaction. Further, we show that reducing pulmonary lipid clearance by targeted deletion of the lipid efflux transporter ATP-binding cassette subfamily G member 1 increases foam cell formation and worsens lung fibrosis after bleomycin. Conversely, we found that treatment with granulocyte-macrophage colony-stimulating factor attenuates fibrotic responses, at least in part through its ability to decrease AM lipid accumulation. In summary, this work describes a novel mechanism leading to foam cell formation in the mouse lung and suggests that strategies aimed at blocking foam cell formation might be effective for treating fibrotic lung disorders.
C1 [Romero, Freddy; Shah, Dilip; Duong, Michelle; Penn, Raymond B.; Stafstrom, William; Kavuru, Mani; Summer, Ross] Thomas Jefferson Univ, Ctr Translat Med, Philadelphia, PA 19107 USA.
[Romero, Freddy; Shah, Dilip; Duong, Michelle; Penn, Raymond B.; Stafstrom, William; Kavuru, Mani; Summer, Ross] Thomas Jefferson Univ, Jane & Leonard Korman Lung Ctr, Philadelphia, PA 19107 USA.
[Lu, Bo] Thomas Jefferson Univ, Bodine Canc Ctr, Philadelphia, PA 19107 USA.
[Kallen, Caleb B.] Thomas Jefferson Univ, Dept Obstet & Gynecol, Philadelphia, PA 19107 USA.
[Fessler, Michael B.; Madenspacher, Jennifer] NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA.
[Walsh, Kenneth] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA.
RP Summer, R (reprint author), Thomas Jefferson Univ, Ctr Translat Med, 1020 Locust St,JAH 368-F, Philadelphia, PA 19107 USA.
EM Ross.Summer@jefferson.edu
OI Kallen, Caleb/0000-0002-4156-6719
FU National Institutes of Health [R01HL105490]; Intramural Research Program
of the National Institutes of Health, National Institute of
Environmental Health Sciences [Z01 ES102005]
FX This work was supported by National Institutes of Health grant
R01HL105490 and by Intramural Research Program of the National
Institutes of Health, National Institute of Environmental Health
Sciences grant Z01 ES102005.
NR 50
TC 3
Z9 5
U1 1
U2 8
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1044-1549
EI 1535-4989
J9 AM J RESP CELL MOL
JI Am. J. Respir. Cell Mol. Biol.
PD JUL
PY 2015
VL 53
IS 1
BP 74
EP 86
DI 10.1165/rcmb.2014-0343OC
PG 13
WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
GA CS5NR
UT WOS:000362125500010
PM 25409201
ER
PT J
AU Pinal-Fernandez, I
Pallisa-Nunez, E
Selva-O'Callaghan, A
Castella-Fierro, E
Simeon-Aznar, CP
Fonollosa-Pla, V
Vilardell-Tarres, M
AF Pinal-Fernandez, I.
Pallisa-Nunez, E.
Selva-O'Callaghan, A.
Castella-Fierro, E.
Simeon-Aznar, C. P.
Fonollosa-Pla, V.
Vilardell-Tarres, M.
TI Pleural irregularity, a new ultrasound sign for the study of
interstitial lung disease in systemic sclerosis and antisynthetase
syndrome
SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY
LA English
DT Article
DE pleural irregularity; interstitial lung disease; systemic sclerosis;
inflammatory myopathy; antisynthetase syndrome; ultrasound
ID RESOLUTION COMPUTED-TOMOGRAPHY; SCLERODERMA; CLASSIFICATION; FIBROSIS;
CT
AB Objective. To evaluate a new ultrasound sign, pleural irregularity (PI), for the study of interstitial lung disease (ILD) in patients with systemic sclerosis (SSc) and antisynthetase syndrome (ASS).
Methods. The study included patients from our SSc and ASS cohorts with varying degrees of ILD, enrolled from 2011 to 2014. Chest high-resolution computed tomography (HRCT), pulmonary function tests (FVC and DLCO) and chest sonography were performed in each patient. Ultrasound PI and B-lines were quantified using a 72-sonographic point score and HRCT lung abnormalities were quantified using Warrick and Wells scores and categorised through Goh's algorithm. PI was correlated with HRCT and pulmonary function test parameters and its diagnostic performance to detect and classify the extent. of ILD was evaluated and compared with B-lines.
Results. Thirty-seven patients were studied, 21 with ASS and 16 with SSc (8 without ILD). PI correlated with the Warrick score both in SSc (r=0.6, p=0.01) and ASS patients (r=0.6, p=0005), showing a higher performance to detect ILD than using B-lines (p=0.01). In SSc patients PI also correlated with Wells score (r=0.7, p<0.001) and with DLCO (r=0.5, p=0.05), showing a high diagnostic value for detecting ILD (AUC=0.85, 95% CI 0.64-1) and classifying it into limited or extensive (AUC=0.81, 95% CI 0.57-1). A modification of the Goh algorithm including PI was developed as a screening tool to avoid the use of HRCT in SSc patients without ultrasound evidence of extensive ILD.
Conclusion. PI is useful for evaluation of ILD in SSc and ASS patients, and can be incorporated into a diagnostic algorithm in SSc patients to reducing the need for exposure to ionising radiation.
C1 [Pinal-Fernandez, I.; Selva-O'Callaghan, A.; Simeon-Aznar, C. P.; Fonollosa-Pla, V.; Vilardell-Tarres, M.] Univ Autonoma Barcelona, Autoimmune Syst Dis Unit, Dept Internal Med, E-08193 Barcelona, Spain.
[Pallisa-Nunez, E.; Castella-Fierro, E.] Univ Autonoma Barcelona, Dept Radiol, Vall dHebron Univ Hosp, E-08193 Barcelona, Spain.
[Pinal-Fernandez, I.] NIAMSD, NIH, Bethesda, MD 20892 USA.
RP Pinal-Fernandez, I (reprint author), NIAMSD, Muscle Dis Unit, Lab Muscle Stem Cells & Gene Express, NIH, 50 South Dr,Room 1141,Bldg 50,MSC 8024, Bethesda, MD 20892 USA.
EM iago.pinalfernandez@nih.gov
NR 23
TC 5
Z9 6
U1 0
U2 0
PU CLINICAL & EXPER RHEUMATOLOGY
PI PISA
PA VIA SANTA MARIA 31, 56126 PISA, ITALY
SN 0392-856X
J9 CLIN EXP RHEUMATOL
JI Clin. Exp. Rheumatol.
PD JUL-AUG
PY 2015
VL 33
IS 4
SU 91
BP S136
EP S141
PG 6
WC Rheumatology
SC Rheumatology
GA CS7BD
UT WOS:000362237600023
PM 26315813
ER
PT J
AU Flegel, WA
Gottschall, JL
Denomme, GA
AF Flegel, Willy A.
Gottschall, Jerome L.
Denomme, Gregory A.
TI Integration of red cell genotyping into the blood supply chain: a
population-based study
SO LANCET HAEMATOLOGY
LA English
DT Article
ID TRANSFUSION SERVICE; BLACK INDIVIDUALS; ALLOIMMUNIZATION; PHENOTYPE;
TRANSPLANTATION; EXPRESSION; ANTIGENS; DISEASE; DONORS; GENE
AB Background When problems with compatibility arise, transfusion services often use time-consuming serological tests to identify antigen-negative red cell units for safe transfusion. New methods have made red cell genotyping possible for all clinically relevant blood group antigens. We did mass-scale genotyping of donor blood and provided hospitals with access to a large red cell database to meet the demand for antigen-negative red cell units beyond ABO and Rh blood typing.
Methods We established a red cell genotype database at the BloodCenter of Wisconsin on July 17, 2010. All self-declared African American, Asian, Hispanic, and Native American blood donors were eligible irrespective of their ABO and Rh type or history of donation. Additionally, blood donors who were groups O, A, and B, irrespective of their Rh phenotype, were eligible for inclusion only if they had a history of at least three donations in the previous 3 years, with one donation in the previous 12 months at the BloodCenter of Wisconsin. We did red cell genotyping with a nanofluidic microarray system, using 32 single nucleotide polymorphisms to predict 42 blood group antigens. An additional 14 antigens were identified via serological phenotype. We monitored the ability of the red cell genotype database to meet demand for compatible blood during 3 years. In addition to the central database at the BloodCenter of Wisconsin, we gave seven hospitals online access to a web-based antigen query portal on May 1, 2013, to help them to locate antigen-negative red cell units in their own inventories.
Findings We analysed genotype data for 43 066 blood donors. Requests were filled for 5661 (99.8%) of 5672 patient encounters in which antigen-negative red cell units were needed. Red cell genotyping met the demand for antigen-negative blood in 5339 (94.1%) of 5672 patient encounters, and the remaining 333 (5.9%) requests were filled by use of serological data. Using the 42 antigens represented in our red cell genotype database, we were able to fill 14 357 (94.8%) of 15 140 requests for antigen-negative red cell units from hospitals served by the BloodCenter of Wisconsin. In the pilot phase, the seven hospitals identified 71 units from 52 antigen-negative red cell unit requests.
Interpretation Red cell genotyping has the potential to transform the way antigen-negative red cell units are provided. An antigen query portal could reduce the need for transportation of blood and serological screening. If this wealth of genotype data can be made easily accessible online, it will help with the supply of affordable antigen-negative red cell units to ensure patient safety.
C1 [Flegel, Willy A.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Gottschall, Jerome L.] Med Coll Wisconsin, Dept Pathol, Milwaukee, WI 53226 USA.
[Gottschall, Jerome L.; Denomme, Gregory A.] BloodCtr Wisconsin, Diagnost Labs, Milwaukee, WI 53201 USA.
RP Denomme, GA (reprint author), BloodCtr Wisconsin, Diagnost Labs, Milwaukee, WI 53201 USA.
EM greg.denomme@bcw.edu
OI Denomme, Gregory/0000-0001-8727-1679
FU BloodCenter of Wisconsin Diagnostic Laboratories Strategic Initiative;
Intramural Research Program of the NIH Clinical Center
FX This work was supported by a BloodCenter of Wisconsin Diagnostic
Laboratories Strategic Initiative and the Intramural Research Program of
the NIH Clinical Center. We thank Harvey G Klein for discussing and
reviewing the manuscript; Craig Beczkiewicz, David Allen Stiles, and
Steven Reinders for computational assistance; and Michael Schanen, Cindy
Piefer, Kathleen Bensing, and the Immunohematology Reference Laboratory
staff for red cell genotyping.
NR 40
TC 10
Z9 11
U1 2
U2 4
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2352-3026
J9 LANCET HAEMATOL
JI Lancet Haematol.
PD JUL
PY 2015
VL 2
IS 7
BP E282
EP E288
DI 10.1016/S2352-3026(15)00090-3
PG 7
WC Hematology
SC Hematology
GA CS4VG
UT WOS:000362073500007
PM 26207259
ER
PT J
AU Hoopes, SL
Garcia, V
Edin, ML
Schwartzman, ML
Zeldin, DC
AF Hoopes, Samantha L.
Garcia, Victor
Edin, Matthew L.
Schwartzman, Michal L.
Zeldin, Darryl C.
TI Vascular actions of 20-HETE
SO PROSTAGLANDINS & OTHER LIPID MEDIATORS
LA English
DT Review
DE 20-HETE; Renin-angiotensin system; Vascular remodeling; Vascular
dysfunction; Vascular inflammation; Angiogenesis
ID SPONTANEOUSLY HYPERTENSIVE-RATS; RENIN-ANGIOTENSIN SYSTEM;
SMOOTH-MUSCLE-CELLS; 20-HYDROXYEICOSATETRAENOIC ACID SYNTHESIS; ARTERY
ENDOTHELIAL-CELLS; ARACHIDONIC-ACID; OXIDATIVE STRESS; BLOOD-VESSELS;
LUMEN FORMATION; NITRIC-OXIDE
AB 20-hydroxyeicosatetraenoic acid (20-HETE) is a metabolite of arachidonic acid that exhibits a myriad of biological effects in the vascular system. This review discusses the current knowledge related to the effects of 20-HETE on vascular reactivity, activation, and remodeling, as well as its role in vascular inflammation and angiogenesis. The information explaining how 20-HETE and the renin-angiotensin system interact to promote hypertension, vasoconstriction, and vascular dysfunction is summarized in this article. 20-HETE enhances vascular inflammation and injury in models of diabetes, ischemia/reperfusion, and cerebrovascular oxidative stress. Recent studies also established a role for 20-HETE in normal and pathological angiogenesis conditions. This review will also discuss the molecular mechanisms through which 20-HETE induces these vascular actions. Potential additional studies are suggested to address shortcomings in the current knowledge of 20-HETE in the vascular system. Published by Elsevier Inc.
C1 [Hoopes, Samantha L.; Edin, Matthew L.; Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA.
[Garcia, Victor; Schwartzman, Michal L.] New York Med Coll, Dept Pharmacol, Valhalla, NY 10595 USA.
RP Zeldin, DC (reprint author), NIEHS, NIH, 111 TW Alexander Dr,Bldg 101,A214, Res Triangle Pk, NC 27709 USA.
EM zeldin@niehs.nih.gov
OI Edin, Matthew/0000-0002-7042-500X
FU Intramural Research Program of the National Institutes of Health,
National Institute of Environmental Health Sciences [Z01 ES025034];
Diversity Supplement Award [HL34300-26A1S1]; NIH [HL034300]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Environmental
Health Sciences (Z01 ES025034 to D.C.Z.), NIH HL034300 (to M.L.S.) and a
Diversity Supplement Award HL34300-26A1S1 (to V.G.)
NR 114
TC 12
Z9 12
U1 0
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1098-8823
EI 2212-196X
J9 PROSTAG OTH LIPID M
JI Prostaglandins Other Lipid Mediat.
PD JUL
PY 2015
VL 120
SI SI
BP 9
EP 16
DI 10.1016/j.prostaglandins.2015.03.002
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CS5UB
UT WOS:000362142700003
PM 25813407
ER
PT J
AU Vanella, L
Canestraro, M
Lee, CR
Cao, J
Zeldin, DC
Schwartzman, ML
Abraham, NG
AF Vanella, Luca
Canestraro, Martina
Lee, Craig R.
Cao, Jian
Zeldin, Darryl C.
Schwartzman, Michal L.
Abraham, Nader G.
TI Soluble epoxide hydrolase null mice exhibit female and male differences
in regulation of vascular homeostasis
SO PROSTAGLANDINS & OTHER LIPID MEDIATORS
LA English
DT Article
DE pAKT; pAMPK; Adiponectin; EETs
ID NITRIC-OXIDE SYNTHASE; II-DEPENDENT HYPERTENSION; LOWERS BLOOD-PRESSURE;
HIGH-FAT DIET; EPOXYEICOSATRIENOIC ACIDS; 20-HYDROXYEICOSATETRAENOIC
ACID; ENDOTHELIAL DYSFUNCTION; HEME-OXYGENASE; CARDIOVASCULAR-DISEASE;
GENDER-DIFFERENCES
AB Increased CYP epoxygenase activity and consequently up regulation of epoxyeicosatrienoic acids (EETs) levels provides protection against metabolic syndrome and cardiovascular diseases. Conversion of arachidonic acid epoxides to diols by soluble epoxide hydrolase (sEH) diminishes the beneficial cardiovascular properties of these epoxyeicosanoids. We therefore examined the possible biochemical consequences of sEH deletion on vascular responses in male and female mice. Through the use of the sEH KO mouse, we provide evidence of differences in the compensatory response in the balance between nitric oxide (NO), carbon monoxide (CO), EETs and the vasoconstrictor 20-HETE in male and female KO mice. Serum levels of adiponectin, TNF alpha, IL-1b and MCP1 and protein expression in vascular tissue of p-AMPK, p-AKT and p-eNOS were measured. Deletion of sEH caused a significant (p <0.05) decrease in body weight, and an increase in adiponectin, pAMPK and pAKT levels in female KO mice compared to male KO mice. Gene deletion resulted in a higher production of renal EETs in female KO compared to male KO mice and, concomitantly, we observed an increase in renal 20-HETEs levels and superoxide anion production only in male KO mice. sEH deletion increased p-AKT and p-eNOS protein expression but decreased p-AMPK levels in female KO mice. Increased levels of p-eNOS at Thr-495 were observed only in KO male mice. While p-eNOS at 1177 were not significantly different between male and female. Nitric oxide production was unaltered in male KO mice. These results provide evidence of gender differences in the preservation of vascular homeostasis in response to sEH deletion which involves regulation of phosphorylation of eNOS at the 495 site. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Vanella, Luca; Canestraro, Martina; Schwartzman, Michal L.; Abraham, Nader G.] New York Med Coll, Dept Pharmacol, Valhalla, NY 10595 USA.
[Vanella, Luca] Univ Catania, Dept Drug Sci, Catania, Italy.
[Lee, Craig R.; Zeldin, Darryl C.] NIEHS, Div Intramural Res, Res Triangle Pk, NC 27709 USA.
[Cao, Jian] Chinese Peoples Liberat Army Gen Hosp, Beijing 100853, Peoples R China.
[Abraham, Nader G.] Marshall Univ, Joan C Edwards Sch Med, Dept Internal Med, Huntington, WV 25701 USA.
RP Abraham, NG (reprint author), New York Med Coll, Med & Pharmacol, Valhalla, NY 10595 USA.
EM nader_abraham@nymc.edu
RI Vanella, Luca/J-7354-2016;
OI Vanella, Luca/0000-0002-6314-6029; Lee, Craig/0000-0003-3595-5301
FU National Institutes of Health grants [HL55601, HL34300]; National
Institute of Environmental Health Sciences [Z01 ES025034]
FX All authors have read and agreed with the manuscript as written. This
work was supported by National Institutes of Health grants (HL55601,
HL34300 to NGA), National Institute of Environmental Health Sciences,
Z01 ES025034 to DZ.
NR 65
TC 2
Z9 2
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1098-8823
EI 2212-196X
J9 PROSTAG OTH LIPID M
JI Prostaglandins Other Lipid Mediat.
PD JUL
PY 2015
VL 120
SI SI
BP 139
EP 147
DI 10.1016/j.prostaglandins.2015.04.004
PG 9
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CS5UB
UT WOS:000362142700018
PM 25908301
ER
PT J
AU Jerome, GJ
Ko, SU
Kauffman, D
Studenski, SA
Ferrucci, L
Simonsick, EM
AF Jerome, Gerald J.
Ko, Seung-uk
Kauffman, Danielle
Studenski, Stephanie A.
Ferrucci, Luigi
Simonsick, Eleanor M.
TI Gait characteristics associated with walking speed decline in older
adults: Results from the Baltimore Longitudinal Study of Aging (vol 60,
pg 239, 2015)
SO ARCHIVES OF GERONTOLOGY AND GERIATRICS
LA English
DT Correction
C1 [Jerome, Gerald J.] Towson Univ, Dept Kinesiol, Towson, MD 21252 USA.
[Ko, Seung-uk] Chonnam Natl Univ, Dept Mech Engn, Yeosu, South Korea.
[Kauffman, Danielle; Studenski, Stephanie A.; Ferrucci, Luigi; Simonsick, Eleanor M.] NIA, Longitudinal Studies Sect, NIH, Baltimore, MD 21224 USA.
RP Jerome, GJ (reprint author), Towson Univ, Dept Kinesiol, Towson, MD 21252 USA.
EM gjerome@towson.edu
NR 1
TC 0
Z9 0
U1 2
U2 3
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0167-4943
EI 1872-6976
J9 ARCH GERONTOL GERIAT
JI Arch. Gerontol. Geriatr.
PD JUL-AUG
PY 2015
VL 61
IS 1
BP 115
EP 115
DI 10.1016/j.archger.2015.04.004
PG 1
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA CS1QF
UT WOS:000361841700019
ER
PT J
AU Flegel, WA
Castilho, L
Delaney, M
Klapper, EB
Moulds, JM
Noizat-Pirenne, F
Shehata, N
Stack, G
Tormey, CA
Wagner, FF
Waxman, DA
Weinstock, C
Wendel, S
Denomme, GA
AF Flegel, Willy A.
Castilho, Lilian
Delaney, Meghan
Klapper, Ellen B.
Moulds, Joann M.
Noizat-Pirenne, France
Shehata, Nadine
Stack, Gary
Tormey, Christopher A.
Wagner, Franz F.
Waxman, Dan A.
Weinstock, Christof
Wendel, Silvano
Denomme, Gregory A.
TI Molecular immunohaematology round table discussions at the AABB Annual
Meeting, Denver 2013
SO BLOOD TRANSFUSION
LA English
DT Editorial Material
ID RED-CELL ALLOIMMUNIZATION; BLOOD; TRANSFUSION; RECOMMENDATIONS;
ANTIBODIES; PHENOTYPES; PREGNANCY; ANTIGENS
C1 [Flegel, Willy A.] NIH, Dept Transfus Med, NIH Clin Ctr, Bethesda, MD 20892 USA.
[Castilho, Lilian] Univ Estadual Campinas, Campinas, SP, Brazil.
[Delaney, Meghan] Puget Sound Blood Ctr, Seattle, WA 98104 USA.
[Klapper, Ellen B.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
[Moulds, Joann M.] Lifeshare Blood Ctr, Shreveport, LA USA.
[Noizat-Pirenne, France] EFS Ile de France, Creteil, France.
[Shehata, Nadine] Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada.
[Stack, Gary; Tormey, Christopher A.] Yale Univ, Sch Med, New Haven, CT USA.
[Wagner, Franz F.] German Red Cross Blood Serv NSTOB, Springe, Germany.
[Waxman, Dan A.] Indiana Blood Ctr, Indianapolis, IN USA.
[Weinstock, Christof] German Red Cross Blood Serv Baden Wurttemberg Hes, Inst Clin Transfus Med & Immunogenet Ulm, Ulm, Germany.
[Weinstock, Christof] Univ Ulm, D-89069 Ulm, Germany.
[Wendel, Silvano] Hosp Sirio Libanes, Sao Paulo, Brazil.
[Denomme, Gregory A.] Blood Ctr Wisconsin, Milwaukee, WI USA.
RP Flegel, WA (reprint author), NIH, Dept Transfus Med, Ctr Clin, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM waf@nih.gov
RI Stack, Gary/E-9646-2014;
OI Stack, Gary/0000-0002-6501-7255; Denomme, Gregory/0000-0001-8727-1679
FU Intramural NIH HHS
NR 23
TC 1
Z9 1
U1 0
U2 3
PU SIMITI SERVIZI SRL
PI MILAN
PA VIA DESIDERIO 21, MILAN, 20131, ITALY
SN 1723-2007
J9 BLOOD TRANSFUS-ITALY
JI Blood Transf.
PD JUL
PY 2015
VL 13
IS 3
BP 514
EP 520
DI 10.2450/2014.0213-14
PG 7
WC Hematology
SC Hematology
GA CS1UD
UT WOS:000361852500023
PM 25545874
ER
PT J
AU Barnhart, KT
DeCherney, AH
AF Barnhart, Kurt T.
DeCherney, Alan H.
TI Are reproductive endocrinologists still gynecologists?
SO FERTILITY AND STERILITY
LA English
DT Editorial Material
C1 [Barnhart, Kurt T.] Univ Penn, Dept Obstet & Gynecol, Perelman Sch Med, Div Reprod Endocrinol & Infertil, Philadelphia, PA 19104 USA.
[DeCherney, Alan H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Reprod Biol & Med Branch, Program Reprod & Adult Endocrinol, Bethesda, MD USA.
RP Barnhart, KT (reprint author), Univ Penn, Dept Obstet & Gynecol, Perelman Sch Med, Div Reprod Endocrinol & Infertil, Philadelphia, PA 19104 USA.
NR 1
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD JUL
PY 2015
VL 104
IS 1
BP 24
EP 25
DI 10.1016/j.fertnstert.2015.04.034
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA CS1RF
UT WOS:000361844700007
PM 25989974
ER
PT J
AU Messinger, LB
Alford, CE
Csokmay, JM
Henne, MB
Mumford, SL
Segars, JH
Armstrong, AY
AF Messinger, Lauren B.
Alford, Connie E.
Csokmay, John M.
Henne, Melinda B.
Mumford, Sunni L.
Segars, James H.
Armstrong, Alicia Y.
TI Cost and efficacy comparison of in vitro fertilization and tubal
anastomosis for women after tubal ligation
SO FERTILITY AND STERILITY
LA English
DT Article
DE In vitro fertilization (IVF); bilateral tubal anastomosis (BTA); tubal
reversal; decision tree; cost effectiveness
ID OVARIAN HYPERSTIMULATION SYNDROME; MICROSURGICAL REVERSAL; ECTOPIC
PREGNANCY; STERILIZATION; MANAGEMENT; REANASTOMOSIS; LAPAROSCOPY; IVF
AB Objective: To compare cost and efficacy of tubal anastomosis to in vitro fertilization (IVF) in women who desired fertility after a tubal ligation.
Design: Cost-effectiveness analysis.
Setting: Not applicable.
Patient(s): Not applicable.
Intervention(s): Not applicable.
Main Outcome Measure(s): Cost per ongoing pregnancy.
Result(s): Cost per ongoing pregnancy for women after tubal anastomosis ranged from $16,446 to $223,482 (2014 USD), whereas IVF ranged from $32,902 to $111,679 (2014 USD). Across maternal age groups <35 and 35-40, years tubal anastomosis was more cost effective than IVF for ongoing pregnancy. Sensitivity analyses validated these findings across a wide range of ongoing pregnancy probabilities as well as costs per procedure.
Conclusion(s): Tubal anastomosis was the most cost-effective approach for most women less than 41 years of age, whereas IVF was the most cost-effective approach for women aged >= 41 years who desired fertility after tubal ligation. A model was created that can be modified based on cost and success rates in individual clinics for improved patient counseling. (C)2015 by American Society for Reproductive Medicine.
C1 [Messinger, Lauren B.] St Vincent Womens Hosp, Dept Obstet & Gynecol, Indianapolis, IN USA.
[Alford, Connie E.] South Florida Inst Reprod Med, Naples, FL USA.
[Csokmay, John M.] Walter Reed Natl Mil Med Ctr, Dept Obstet & Gynecol, Div Reprod Endocrinol, Bethesda, MD USA.
[Henne, Melinda B.] Reprod Med Associates Texas, San Antonio, TX USA.
[Mumford, Sunni L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, NIH, Bethesda, MD USA.
[Segars, James H.] Johns Hopkins Univ, Dept Obstet & Gynecol, Reprod Sci & Womens Hlth Res, Baltimore, MD USA.
[Armstrong, Alicia Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
RP Messinger, LB (reprint author), 8111 Township Line Rd, Indianapolis, IN 46260 USA.
EM lmessing@stvincent.org
FU Program in Reproductive Adult Endocrinology; Intramural Research Program
of the Eunice Kennedy Shriver National Institute of Child Health and
Human Development at the National Institutes of Health, Bethesda,
Maryland
FX Supported, in part, by the Program in Reproductive Adult Endocrinology
and the Intramural Research Program of the Eunice Kennedy Shriver
National Institute of Child Health and Human Development at the National
Institutes of Health, Bethesda, Maryland.
NR 47
TC 2
Z9 3
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD JUL
PY 2015
VL 104
IS 1
BP 32
EP +
DI 10.1016/j.fertnstert.2015.04.019
PG 11
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA CS1RF
UT WOS:000361844700010
PM 26006734
ER
PT J
AU Hwang, JP
Somerfield, MR
Alston-Johnson, DE
Cryer, DR
Feld, JJ
Kramer, BS
Sabichi, AL
Wong, SL
Artz, AS
AF Hwang, Jessica P.
Somerfield, Mark R.
Alston-Johnson, Devena E.
Cryer, Donna R.
Feld, Jordan J.
Kramer, Barnett S.
Sabichi, Anita L.
Wong, Sandra L.
Artz, Andrew S.
TI Hepatitis B Virus Screening for Patients With Cancer Before Therapy:
American Society of Clinical Oncology Provisional Clinical Opinion
Update
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID TASK-FORCE RECOMMENDATION; COST-EFFECTIVENESS; CYTOTOXIC CHEMOTHERAPY;
FOLLICULAR LYMPHOMA; REACTIVATION; INFECTION; LAMIVUDINE; RITUXIMAB;
PROPHYLAXIS; MANAGEMENT
AB Purpose This updated provisional clinical opinion presents a revised opinion based on American Society of Clinical Oncology panel consensus in the context of an evolving database.
Context Despite the 2010 provisional clinical opinion recommendation, there is still evidence of suboptimal hepatitis B virus (HBV) screening among patients at high risk for HBV infection or HBV reactivation after chemotherapy. This updated provisional clinical opinion introduces a risk-adaptive strategy to identify and treat patients with HBV infection to reduce their risk of HBV reactivation.
Provisional Clinical Opinion Medical providers should screen by testing patients for HBV infection before starting anti-CD20 therapy or hematopoietic cell transplantation. Providers should also screen patients with risk factors for HBV infection. Screening should include both hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc), because reactivation can occur in patients who are HBsAg positive/anti-HBc positive or HBsAg negative/anti-HBc positive. Either total anti-HBc or anti-HBc immunoglobulin G (not immunoglobulin M) test should be used. Clinicians should start antiviral therapy for HBsAg-positive/anti-HBc-positive patients before or contemporaneously with cancer therapy and monitor HBsAg-negative/anti-HBc-positive patients for reactivation with HBV DNA and ALT levels, promptly starting antivirals if reactivation occurs. Clinicians can initiate antivirals for HBsAg-negative/anti-HBc-positive patients anticipating cancer therapies associated with a high risk of reactivation, or they can monitor HBV DNA and ALT levels and initiate on-demand antivirals. For patients who neither have HBV risk factors nor anticipate cancer therapy associated with a high risk of reactivation, current evidence does not support HBV screening before initiation of cancer therapy. Two panel members provided a minority viewpoint, involving a strategy of universal HBsAg and selective anti-HBc testing.
C1 [Hwang, Jessica P.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Sabichi, Anita L.] Baylor Coll Med, Houston, TX 77030 USA.
[Somerfield, Mark R.] Amer Soc Clin Oncol, Alexandria, VA 22314 USA.
[Alston-Johnson, Devena E.] Upstate Oncol Associates, Greenville, SC USA.
[Cryer, Donna R.] Global Liver Inst, Washington, DC USA.
[Feld, Jordan J.] Toronto Western Hosp, Ctr Liver, Toronto, ON M5T 2S8, Canada.
[Kramer, Barnett S.] NCI, Bethesda, MD 20892 USA.
[Wong, Sandra L.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Artz, Andrew S.] Univ Chicago, Chicago, IL 60637 USA.
RP Hwang, JP (reprint author), Amer Soc Clin Oncol, 2318 Mill Rd,Suite 800, Alexandria, VA 22314 USA.
EM guidelines@asco.org
FU NCATS NIH HHS [UL1 TR000430]
NR 41
TC 21
Z9 21
U1 0
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 JUL 1
PY 2015
VL 33
IS 19
BP 2212
EP U128
DI 10.1200/JCO.2015.61.3745
PG 11
WC Oncology
SC Oncology
GA CR8UV
UT WOS:000361630500014
PM 25964247
ER
PT J
AU Resnik, DB
Wager, E
Kissling, GE
AF Resnik, David B.
Wager, Elizabeth
Kissling, Grace E.
TI Retraction policies of top scientific journals ranked by impact factor
SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION
LA English
DT Article
DE Retractions of Publications; Journal Policies; Ethics; Misconduct
ID ARTICLES
AB Objective: This study gathered information about the retraction policies of the top 200 scientific journals, ranked by impact factor.
Methods: Editors of the top 200 science journals for the year 2012 were contacted by email.
Results: One hundred forty-seven journals (74%) responded to a request for information. Of these, 95 (65%) had a retraction policy. Of journals with a retraction policy, 94% had a policy that allows the editors to retract articles without authors' consent.
Conclusions: The majority of journals in this sample had a retraction policy, and almost all of them would retract an article without the authors' permission.
C1 [Resnik, David B.; Kissling, Grace E.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
RP Resnik, DB (reprint author), NIEHS, NIH, 111 Alexander Dr,POB 12233,Mail Drop CU 03, Res Triangle Pk, NC 27709 USA.
EM resnikd@niehs.nih.gov; liz@sideview.demon.co.uk; kissling@niehs.nih.gov
OI Wager, Elizabeth/0000-0002-4202-7813
NR 14
TC 2
Z9 2
U1 4
U2 21
PU MEDICAL LIBRARY ASSOC
PI CHICAGO
PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA
SN 1536-5050
J9 J MED LIBR ASSOC
JI J. Med. Libr. Assoc.
PD JUL
PY 2015
VL 103
IS 3
BP 136
EP 139
DI 10.3163/1536-5050.103.3.006
PG 4
WC Information Science & Library Science
SC Information Science & Library Science
GA CR7RH
UT WOS:000361547700006
PM 26213505
ER
PT J
AU Dritsou, V
Topalis, P
Windbichler, N
Simoni, A
Hall, A
Lawson, D
Hinsley, M
Hughes, D
Napolioni, V
Crucianelli, F
Deligianni, E
Gasperi, G
Gomulski, LM
Savini, G
Manni, M
Scolari, F
Malacrida, AR
Arca, B
Ribeiro, JM
Lombardo, F
Saccone, G
Salvemini, M
Moretti, R
Aprea, G
Calvitti, M
Picciolini, M
Papathanos, PA
Spaccapelo, R
Favia, G
Crisanti, A
Louis, C
AF Dritsou, Vicky
Topalis, Pantelis
Windbichler, Nikolai
Simoni, Alekos
Hall, Ann
Lawson, Daniel
Hinsley, Malcolm
Hughes, Daniel
Napolioni, Valerio
Crucianelli, Francesca
Deligianni, Elena
Gasperi, Giuliano
Gomulski, Ludvik M.
Savini, Grazia
Manni, Mose
Scolari, Francesca
Malacrida, Anna R.
Arca, Bruno
Ribeiro, Jose M.
Lombardo, Fabrizio
Saccone, Giuseppe
Salvemini, Marco
Moretti, Riccardo
Aprea, Giuseppe
Calvitti, Maurizio
Picciolini, Matteo
Papathanos, Philippos Aris
Spaccapelo, Roberta
Favia, Guido
Crisanti, Andrea
Louis, Christos
TI A draft genome sequence of an invasive mosquito: an Italian Aedes
albopictus
SO PATHOGENS AND GLOBAL HEALTH
LA English
DT Article
DE NGS; WGS; BUSCO; Repetitive DNA; Transposable elements; Invasive
species; Disease vector; Dengue fever; Chikungunya
ID ODORANT-BINDING-PROTEINS; ASIAN TIGER MOSQUITO; ADULT FEMALE MOSQUITO;
TRANSFER-RNA GENES; DIPTERA-CULICIDAE; ANOPHELES-GAMBIAE; CYTOPLASMIC
INCOMPATIBILITY; CULEX-QUINQUEFASCIATUS; AEGYPTI; IDENTIFICATION
AB The draft genome sequence of Italian specimens of the Asian tiger mosquito Aedes (Stegomyia) albopictus (Diptera: Culicidae) was determined using a standard NGS (next generation sequencing) approach. The size of the assembled genome is comparable to that of Aedes aegypti; the two mosquitoes are also similar as far as the high content of repetitive DNA is concerned, most of which is made up of transposable elements. Although, based on BUSCO (Benchmarking Universal Single-Copy Orthologues) analysis, the genome assembly reported here contains more than 99% of protein-coding genes, several of those are expected to be represented in the assembly in a fragmented state. We also present here the annotation of several families of genes (tRNA genes, miRNA genes, the sialome, genes involved in chromatin condensation, sex determination genes, odorant binding proteins and odorant receptors). These analyses confirm that the assembly can be used for the study of the biology of this invasive vector of disease.
C1 [Dritsou, Vicky; Napolioni, Valerio; Crucianelli, Francesca; Picciolini, Matteo; Crisanti, Andrea] Loc S Andrea Fratte, Polo Innovaz Genom Genet & Biol Polo GGB, Perugia, Italy.
[Topalis, Pantelis; Deligianni, Elena; Louis, Christos] Fdn Res & Technol Hellas, Inst Mol Biol & Biotechnol, Iraklion, Crete, Greece.
[Windbichler, Nikolai; Simoni, Alekos; Hall, Ann; Papathanos, Philippos Aris; Crisanti, Andrea] Univ London Imperial Coll Sci Technol & Med, Dept Life Sci, London SW7 2AZ, England.
[Lawson, Daniel; Hinsley, Malcolm; Hughes, Daniel] European Bioinformat Inst EMBL EBI, European Mol Biol Lab, Cambridge, Cambs, England.
[Gasperi, Giuliano; Gomulski, Ludvik M.; Savini, Grazia; Manni, Mose; Scolari, Francesca; Malacrida, Anna R.] Univ Pavia, Dept Biol & Biotechnol, I-27100 Pavia, Italy.
[Arca, Bruno; Lombardo, Fabrizio] Univ Roma La Sapienza, Dept Publ Hlth & Infect Dis, Div Parasitol, Rome, Italy.
[Ribeiro, Jose M.] NIAID, Bethesda, MD 20892 USA.
[Saccone, Giuseppe; Salvemini, Marco] Univ Naples Federico II, Dept Biol, Naples, Italy.
[Moretti, Riccardo; Aprea, Giuseppe; Calvitti, Maurizio] ENEA Italian Natl Agcy New Technol Energy & Susta, CR Casaccia, Rome, Italy.
[Papathanos, Philippos Aris; Spaccapelo, Roberta; Crisanti, Andrea; Louis, Christos] Univ Perugia, Dept Expt Med, I-06100 Perugia, Italy.
[Favia, Guido] Univ Camerino, Scuola Biosci & Med Vet, I-62032 Camerino, Italy.
RP Louis, C (reprint author), IMBB FORTH, N Plastira 100, GR-70013 Iraklion, Crete, Greece.
EM louis@imbb.forth.gr
RI saccone, giuseppe/F-8627-2013; Lombardo, Fabrizio/J-8511-2014; Scolari,
Francesca/L-9233-2015;
OI saccone, giuseppe/0000-0002-9835-3693; Lombardo,
Fabrizio/0000-0002-8563-0612; Scolari, Francesca/0000-0003-3085-9038;
Lawson, Daniel/0000-0001-7765-983X; SALVEMINI,
Marco/0000-0003-2297-9267; Ribeiro, Jose/0000-0002-9107-0818
FU Infravec Consortium (FP7 programme of the European Union); Hellenic
Secretariat General for research and Technology; EU; NIAID; Campania
Region [LG5/2001]; University of Naples Federico II; Compagnia di San
Paolo, Naples, ITALY; University of Naples Federico II [STAR2013_25];
Italian Ministry of Health [RF-2010-2318965]
FX This work was funded by the Infravec Consortium (FP7 programme of the
European Union) and, partially, by funds from the Hellenic Secretariat
General for research and Technology. VD and CL were supported, in part,
by i-Move fellowships from the EU's Marie Curie programme. JMR was
funded by the intramural programme of the NIAID. The sex determination
studies were supported by a grant from Campania Region (LG5/2001; 2008;
Biotechnological approaches for the control of the human disease vector
Aedes albopictus) to GS and by a grant from the University of Naples
Federico II and Compagnia di San Paolo, Naples, ITALY, to MS in the
frame of Programme STAR (STAR2013_25) from the University of Naples
Federico II and Compagnia di San Paolo, Naples, ITALY. ARM was funded by
a grant from the Italian Ministry of Health (RF-2010-2318965).
NR 87
TC 5
Z9 5
U1 6
U2 19
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 2047-7724
EI 2047-7732
J9 PATHOG GLOB HEALTH
JI Pathog. Glob. Health
PD JUL
PY 2015
VL 109
IS 5
BP 207
EP 220
DI 10.1179/2047773215Y.0000000031
PG 14
WC Public, Environmental & Occupational Health; Parasitology; Tropical
Medicine
SC Public, Environmental & Occupational Health; Parasitology; Tropical
Medicine
GA CS1AE
UT WOS:000361793100001
PM 26369436
ER
PT J
AU McDermott, MM
Greenland, P
Tian, L
Kibbe, MR
Green, D
Zhao, LH
Criqui, MH
Guralnik, JM
Ferrucci, L
Liu, K
Wilkins, JT
Huffman, MD
Shah, SJ
Liao, YH
Lloyd-Jones, DM
AF McDermott, Mary M.
Greenland, Philip
Tian, Lu
Kibbe, Melina R.
Green, David
Zhao, Lihui
Criqui, Michael H.
Guralnik, Jack M.
Ferrucci, Luigi
Liu, Kiang
Wilkins, John T.
Huffman, Mark D.
Shah, Sanjiv J.
Liao, Yihua
Lloyd-Jones, Donald M.
TI Association of 6-Minute Walk Performance and Physical Activity With
Incident Ischemic Heart Disease Events and Stroke in Peripheral Artery
Disease
SO JOURNAL OF THE AMERICAN HEART ASSOCIATION
LA English
DT Article
DE intermittent claudication; peripheral vascular disease
ID ANKLE-BRACHIAL INDEX; RANDOMIZED CLINICAL-TRIAL; FUNCTIONAL DECLINE;
CARDIOVASCULAR-DISEASE; LEG SYMPTOMS; OLDER-ADULTS; DAILY-LIFE;
MORTALITY; RISK; MOBILITY
AB Background-We determined whether poorer 6-minute walk performance and lower physical activity levels are associated with higher rates of ischemic heart disease (IHD) events in people with lower extremity peripheral artery disease (PAD).
Methods and Results-Five hundred ten PAD participants were identified from Chicago-area medical centers and followed prospectively for 19.0 +/- 9.5 months. At baseline, participants completed the 6-minute walk and reported number of blocks walked during the past week (physical activity). IHD events were systematically adjudicated and consisted of new myocardial infarction, unstable angina, and cardiac death. For 6-minute walk, IHD event rates were 25/170 (14.7%) for the third (poorest) tertile, 10/171 (5.8%%) for the second tertile, and 6/169 (3.5%) for the first (best) tertile (P=0.003). For physical activity, IHD event rates were 21/ 154 (13.6%) for the third (poorest) tertile, 15/174 (8.6%) for the second tertile, and 5/182 (2.7%) for the first (best) tertile (P=0.001). Adjusting for age, sex, race, smoking, body mass index, comorbidities, and physical activity, participants in the poorest 6-minute walk tertile had a 3.28-fold (95% CI 1.17 to 9.17, P=0.024) higher hazard for IHD events, compared with those in the best tertile. Adjusting for confounders including 6-minute walk, participants in the poorest physical activity tertile had a 3.72-fold (95% CI 1.24 to 11.19, P=0.019) higher hazard for IHD events, compared with the highest tertile.
Conclusions-Six-minute walk and physical activity predict IHD event rates in PAD. Further study is needed to determine whether interventions that improve 6-minute walk, physical activity, or both can reduce IHD events in PAD.
C1 [McDermott, Mary M.; Greenland, Philip; Green, David; Liu, Kiang; Wilkins, John T.; Huffman, Mark D.; Shah, Sanjiv J.; Lloyd-Jones, Donald M.] Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA.
[McDermott, Mary M.; Greenland, Philip; Zhao, Lihui; Liu, Kiang; Wilkins, John T.; Huffman, Mark D.; Liao, Yihua; Lloyd-Jones, Donald M.] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA.
[Kibbe, Melina R.] Northwestern Univ, Feinberg Sch Med, Dept Surg, Chicago, IL 60611 USA.
[Tian, Lu] Stanford Univ, Dept Hlth Res & Policy, Stanford, CA 94305 USA.
[Kibbe, Melina R.] Jesse Brown Vet Affairs Med Ctr, Chicago, IL USA.
[Criqui, Michael H.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA.
[Guralnik, Jack M.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Ferrucci, Luigi] NIA, Bethesda, MD 20892 USA.
RP McDermott, MM (reprint author), 750 N Lake Shore Dr,10th Floor, Chicago, IL 60611 USA.
EM mdm608@northwestern.edu
FU National Heart, Lung, and Blood Institute (NHLBI) [R01-HL089619]
FX Funded by the National Heart, Lung, and Blood Institute (NHLBI)
(R01-HL089619).
NR 28
TC 1
Z9 1
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2047-9980
J9 J AM HEART ASSOC
JI J. Am. Heart Assoc.
PD JUL
PY 2015
VL 4
IS 7
AR e001846
DI 10.1161/JAHA.115.001846
PG 11
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CR6WR
UT WOS:000361489400013
ER
PT J
AU Predazzi, IM
Sobota, RS
Sanna, S
Bush, WS
Bartlett, J
Lilley, JS
Linton, MF
Schlessinger, D
Cucca, F
Fazio, S
Williams, SM
AF Predazzi, Irene M.
Sobota, Rafal S.
Sanna, Serena
Bush, William S.
Bartlett, Jacquelaine
Lilley, Jessica S.
Linton, MacRae F.
Schlessinger, David
Cucca, Francesco
Fazio, Sergio
Williams, Scott M.
TI Sex-Specific Parental Effects on Offspring Lipid Levels
SO JOURNAL OF THE AMERICAN HEART ASSOCIATION
LA English
DT Article
DE cholesterol; genetics; lipids; risk factors; sex
ID GENOME-WIDE ASSOCIATION; LOW-DENSITY-LIPOPROTEIN; EARLY ATHEROSCLEROTIC
LESIONS; CORONARY-HEART-DISEASE; OF-ORIGIN; MATERNAL
HYPERCHOLESTEROLEMIA; FAMILIAL HYPERCHOLESTEROLEMIA; INTRAUTERINE
EXPOSURE; HETEROZYGOUS MICE; HUMAN-PREGNANCY
AB Background-Plasma lipid levels are highly heritable traits, but known genetic loci can only explain a small portion of their heritability.
Methods and Results-In this study, we analyzed the role of parental levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TGs) in explaining the values of the corresponding traits in adult offspring. We also evaluated the contribution of nongenetic factors that influence lipid traits (age, body mass index, smoking, medications, and menopause) alone and in combination with variability at the genetic loci known to associate with TC, LDL-C, HDL-C, and TG levels. We performed comparisons among different sex-specific regression models in 416 families from the Framingham Heart Study and 304 from the SardiNIA cohort. Models including parental lipid levels explain significantly more of the trait variation than models without these measures, explaining up to approximate to 39% of the total trait variation. Of this variation, the parent-of-origin effect explains as much as approximate to 15% and it does so in a sex-specific way. This observation is not owing to shared environment, given that spouse-pair correlations were negligible (<1.5% explained variation in all cases) and is distinct from previous genetic and acquired factors that are known to influence serum lipid levels.
Conclusions-These findings support the concept that unknown genetic and epigenetic contributors are responsible for most of the heritable component of the plasma lipid phenotype, and that, at present, the clinical utility of knowing age-matched parental lipid levels in assessing risk of dyslipidemia supersedes individual locus effects. Our results support the clinical utility of knowing parental lipid levels in assessing future risk of dyslipidemia.
C1 [Predazzi, Irene M.; Lilley, Jessica S.; Linton, MacRae F.; Fazio, Sergio] Vanderbilt Univ, Med Ctr, Dept Med, Atherosclerosis Res Unit, Nashville, TN USA.
[Predazzi, Irene M.; Lilley, Jessica S.; Linton, MacRae F.; Fazio, Sergio] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA.
[Sobota, Rafal S.; Bush, William S.] Vanderbilt Univ, Med Ctr, Ctr Human Genet Res, Nashville, TN 37232 USA.
[Predazzi, Irene M.; Fazio, Sergio] Oregon Hlth & Sci Univ, Ctr Prevent Cardiol, Knight Cardiovasc Inst, Portland, OR 97239 USA.
[Sobota, Rafal S.; Bartlett, Jacquelaine; Williams, Scott M.] Dartmouth Coll, Geisel Sch Med, Dept Genet, Hanover, NH 03755 USA.
[Sanna, Serena; Cucca, Francesco] CNR, IRGB, Monserrato, Italy.
[Bush, William S.] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA.
[Lilley, Jessica S.] Univ Mississippi, Sch Med, Dept Pediat, Div Endocrinol, Jackson, MS 39216 USA.
[Schlessinger, David] NIA, Genet Lab, Baltimore, MD 21224 USA.
RP Fazio, S (reprint author), Oregon Hlth & Sci Univ, Ctr Prevent Cardiol Oregon, Knight Cardiovasc Inst, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA.
EM fazio@ohsu.edu
OI Bush, William/0000-0002-9729-6519
FU NIH [2R01HL057986-15A1, 5R01HL106845-03, 2T32HL007751-16A2, P20
GM103534, HL116263]; NIH National Institute of Aging [N01-AG-1-2109];
Sardinian Autonomous Region [cRP3-154, 7/2009]
FX This work was partially funded by grant NIH 2R01HL057986-15A1 and
5R01HL106845-03 (Fazio), NIH 2T32HL007751-16A2 (Predazzi), NIH P20
GM103534 (Williams), NIH HL116263 (Linton), NIH National Institute of
Aging N01-AG-1-2109, N01-AG-1-2109, and Sardinian Autonomous Region
(L.R. no. 7/2009) cRP3-154 (Cucca).
NR 54
TC 2
Z9 2
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2047-9980
J9 J AM HEART ASSOC
JI J. Am. Heart Assoc.
PD JUL
PY 2015
VL 4
IS 7
AR e001951
DI 10.1161/JAHA.115.001951
PG 49
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CR6WR
UT WOS:000361489400023
ER
PT J
AU Cooper, LA
Ortega, AN
Ammerman, AS
Buchwald, D
Paskett, ED
Powell, LH
Thompson, B
Tucker, KL
Warnecke, RB
McCarthy, WJ
Viswanath, KV
Henderson, JA
Calhoun, EA
Williams, DR
AF Cooper, Lisa A.
Ortega, Alexander N.
Ammerman, Alice S.
Buchwald, Dedra
Paskett, Electra D.
Powell, Lynda H.
Thompson, Beti
Tucker, Katherine L.
Warnecke, Richard B.
McCarthy, William J.
Viswanath, K. Vish
Henderson, Jeffrey A.
Calhoun, Elizabeth A.
Williams, David R.
TI Calling for a Bold New Vision of Health Disparities Intervention
Research
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Editorial Material
ID MULTILEVEL; INEQUALITIES; PROTOCOL
C1 [Cooper, Lisa A.; Ortega, Alexander N.; Ammerman, Alice S.; Buchwald, Dedra; Paskett, Electra D.; Powell, Lynda H.; Thompson, Beti; Tucker, Katherine L.; Warnecke, Richard B.; McCarthy, William J.; Viswanath, K. Vish; Henderson, Jeffrey A.; Calhoun, Elizabeth A.; Williams, David R.] NCI, Bethesda, MD 20892 USA.
[Cooper, Lisa A.] Johns Hopkins Univ, Baltimore, MD 21287 USA.
[Ortega, Alexander N.; McCarthy, William J.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Ammerman, Alice S.] Univ N Carolina, Chapel Hill, NC USA.
[Buchwald, Dedra] Univ Washington, Seattle, WA 98195 USA.
[Paskett, Electra D.] Ohio State Univ, Columbus, OH 43210 USA.
[Powell, Lynda H.] Rush Univ, Chicago, IL 60612 USA.
[Tucker, Katherine L.] Univ Massachusetts, Lowell, MA USA.
[Thompson, Beti] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Warnecke, Richard B.] Univ Illinois, Chicago, IL USA.
[Viswanath, K. Vish; Williams, David R.] Harvard Univ, Cambridge, MA 02138 USA.
[Henderson, Jeffrey A.] Black Hills Ctr Amer Indian Hlth, Rapid City, SD USA.
[Calhoun, Elizabeth A.] Univ Arizona, Tucson, AZ USA.
RP Cooper, LA (reprint author), Johns Hopkins Univ, Sch Med, Welch Ctr Prevent Epidemiol & Clin Res, 2024 East Monument St,Suite 2-500, Baltimore, MD 21287 USA.
EM lisa.cooper@jhmi.edu
OI Ortega, Alexander/0000-0001-6861-6993
FU National Heart, Lung, and Blood Institute [P50HL105187, P50HL105188,
P50HL10584, P50HL10585, P50HL105189]; National Cancer Institute
[P50CA148143, P50CA148596, P50CA105632, P50CA106743, P50CA148110]
FX This work was supported by grants from the National Heart, Lung, and
Blood Institute (P50HL105187, P50HL105188, P50HL10584, P50HL10585,
P50HL105189) and the National Cancer Institute (P50CA148143,
P50CA148596, P50CA105632, P50CA106743, P50CA148110). The authors would
like to acknowledge Shobha Srinivasan, PhD, Peter Kaufmann, PhD,
Josephine Boyington, PhD, and Michael Spittel, PhD, for their strong
support of the Centers for Population Health and Health Disparities
program, and Jennifer Halbert and Joy Mays for assistance with the
preparation, coordination, format, and submission of the editorial.
NR 10
TC 11
Z9 11
U1 0
U2 12
PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
EI 1541-0048
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD JUL
PY 2015
VL 105
SU 3
BP S374
EP S376
DI 10.2105/AJPH.2014.302386
PG 3
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CQ9LH
UT WOS:000360935700014
PM 25905830
ER
PT J
AU Dankwa-Mullan, I
Bull, J
Sy, F
AF Dankwa-Mullan, Irene
Bull, Jonca
Sy, Francisco
TI Precision Medicine and Health Disparities: Advancing the Science of
Individualizing Patient Care
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Editorial Material
C1 [Dankwa-Mullan, Irene] NIMHD, Bethesda, MD USA.
[Bull, Jonca] US FDA, Off Minor Hlth, Rockville, MD 20857 USA.
[Sy, Francisco] NIMHD, Off Community Based Participatory Res & Collabora, Bethesda, MD USA.
RP Dankwa-Mullan, I (reprint author), NIMHD, Bethesda, MD USA.
NR 0
TC 1
Z9 2
U1 1
U2 8
PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
EI 1541-0048
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD JUL
PY 2015
VL 105
SU 3
BP S368
EP S368
DI 10.2105/AJPH.2015.302755
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CQ9LH
UT WOS:000360935700011
PM 26039545
ER
PT J
AU Golden, SH
Ferketich, A
Boyington, J
Dugan, S
Garroutte, E
Kaufmann, PG
Krok, J
Kuo, A
Ortega, AN
Purnell, T
Srinivasan, S
AF Golden, Sherita Hill
Ferketich, Amy
Boyington, Josephine
Dugan, Sheila
Garroutte, Eva
Kaufmann, Peter G.
Krok, Jessica
Kuo, Alice
Ortega, Alexander N.
Purnell, Tanjala
Srinivasan, Shobha
TI Transdisciplinary Cardiovascular and Cancer Health Disparities Training:
Experiences of the Centers for Population Health and Health Disparities
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Article
ID CARE; QUALITY; OBESITY; IMPLEMENTATION; INTERVENTION; PARTNERSHIP;
ACCESS; IMPACT; ADULTS; RISK
AB The Centers for Population Health and Health Disparities program promotes multilevel and multifactorial health equity research and the building of research teams that are transdisciplinary. We summarized 5 areas of scientific training for empowering the next generation of health disparities investigators with research methods and skills that are needed to solve disparities and inequalities in cancer and cardiovascular disease. These areas include social epidemiology, multilevel modeling, health care systems or health care delivery, community-based participatory research, and implementation science. We reviewed the acquisition of the skill sets described in the training components; these skill sets will position trainees to become leaders capable of effecting significant change because they provide tools that can be used to address the complexities of issues that promote health disparities.
C1 [Golden, Sherita Hill; Purnell, Tanjala] Johns Hopkins Univ, Sch Med, Baltimore, MD 21287 USA.
[Golden, Sherita Hill; Purnell, Tanjala] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21287 USA.
[Ferketich, Amy] Ohio State Univ, Coll Publ Hlth, Columbus, OH 43210 USA.
[Boyington, Josephine; Kaufmann, Peter G.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Dugan, Sheila] Rush Univ, Med Ctr, Chicago, IL 60612 USA.
[Garroutte, Eva] Boston Coll, Dept Sociol, Chestnut Hill, MA 02167 USA.
[Krok, Jessica] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA.
[Kuo, Alice; Ortega, Alexander N.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA.
[Srinivasan, Shobha] NCI, NIH, Bethesda, MD 20892 USA.
RP Golden, SH (reprint author), Johns Hopkins Univ, Sch Med, Div Endocrinol Diabet & Metab, 1830 E Monument St,Suite 333, Baltimore, MD 21287 USA.
EM sahill@jhmi.edu
OI Ortega, Alexander/0000-0001-6861-6993
FU [P50CA148143-01]; [P50CA148596-01]; [P50HL105187-01];
[P50HL105185-01]; [P50CA105632-06]; [P50HL105189-01];
[P50HL105188-01]; [P50CA106743-06]; [P50HL105184-01];
[P50CA148110-01]
FX Funding Sources: P50CA148143-01, Principal investigator (PI): Beti
Thompson, Understanding and Preventing Breast Cancer Disparities in
Latinas; P50CA148596-01, PI: David R. Williams, Lung Cancer Disparities
Center: Jointly Addressing Race and Socioeconomic Status;
P50HL105187-01, PI: Lisa A. Cooper, Johns Hopkins Center for Eliminating
Cardiovascular Health Disparities; P50HL105185-01, PI: Katheine L.
Tucker, Boston Puerto Rican Health Study -CVD Risk Factors;
P50CA105632-06, PI: Electra D. Paskett, Reducing Cervical Cancer in
Appalachia; P50HL105189-01, PI: Lynda H. Powell, Rush Center for Urban
Health Equity; P50HL105188-01, PI: Alexander N. Ortega, Family and
Neighborhood Interventions to Reduce Heart Disease Risk in East L. A;
P50CA106743-06, PI: Richard Warnecke, UIC Center for Population Health
and Health Disparities; P50HL105184-01, PI: Alice S. Ammerman, Center
for Reduced CVD Disparities: Genes, Clinics, and Communities;
P50CA148110-01, PI: Dedra S. Buchwald, Center for Native Population
Health Disparities.
NR 39
TC 3
Z9 3
U1 3
U2 8
PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
EI 1541-0048
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD JUL
PY 2015
VL 105
SU 3
BP S395
EP S402
DI 10.2105/AJPH.2014.302489
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CQ9LH
UT WOS:000360935700018
PM 25905828
ER
PT J
AU Srinivasan, S
Moser, RP
Willis, G
Riley, W
Alexander, M
Berrigan, D
Kobrin, S
AF Srinivasan, Shobha
Moser, Richard P.
Willis, Gordon
Riley, William
Alexander, Mark
Berrigan, David
Kobrin, Sarah
TI Small Is Essential: Importance of Subpopulation Research in Cancer
Control
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Editorial Material
ID CLUSTER RANDOMIZED-TRIALS; HIDDEN POPULATIONS; INTERVENTIONS;
CHALLENGES; ISLANDERS
C1 [Srinivasan, Shobha; Moser, Richard P.; Willis, Gordon; Riley, William; Alexander, Mark; Berrigan, David; Kobrin, Sarah] NCI, Div Canc Control & Populat Sci, Rockville, MD 20850 USA.
RP Srinivasan, S (reprint author), NCI, Div Canc Control & Populat Sci, 9609 Med Ctr Dr,Room 4E432,MSC 9764, Rockville, MD 20850 USA.
EM ss688k@nih.gov
NR 22
TC 4
Z9 5
U1 0
U2 2
PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
EI 1541-0048
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD JUL
PY 2015
VL 105
SU 3
BP S371
EP S373
DI 10.2105/AJPH.2014.302267
PG 4
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CQ9LH
UT WOS:000360935700013
PM 25905825
ER
PT J
AU Via, LE
England, K
Weiner, DM
Schimel, D
Zimmerman, MD
Dayao, E
Chen, RY
Dodd, LE
Richardson, M
Robbins, KK
Cai, Y
Hammoud, D
Herscovitch, P
Dartois, V
Flynn, JL
Barry, CE
AF Via, Laura E.
England, Kathleen
Weiner, Danielle M.
Schimel, Daniel
Zimmerman, Matthew D.
Dayao, Emmanuel
Chen, Ray Y.
Dodd, Lori E.
Richardson, Mike
Robbins, Katherine K.
Cai, Ying
Hammoud, Dima
Herscovitch, Peter
Dartois, Veronique
Flynn, JoAnne L.
Barry, Clifton E., III
TI A Sterilizing Tuberculosis Treatment Regimen Is Associated with Faster
Clearance of Bacteria in Cavitary Lesions in Marmosets
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID POSITRON-EMISSION-TOMOGRAPHY; PULMONARY TUBERCULOSIS; POPULATION
PHARMACOKINETICS; MYCOBACTERIUM-TUBERCULOSIS; ANTITUBERCULOSIS DRUGS;
COMPUTED-TOMOGRAPHY; CLINICAL-TRIAL; MOUSE MODEL; RIFAMPICIN;
CHEMOTHERAPY
AB Shortening the lengthy treatment duration for tuberculosis patients is a major goal of current drug development efforts. The common marmoset develops human-like disease pathology and offers an attractive model to better understand the basis for relapse and test regimens for effective shorter duration therapy. We treated Mycobacterium tuberculosis-infected marmosets with two drug regimens known to differ in their relapse rates in human clinical trials: the standard four-drug combination of isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) that has very low relapse rates and the combination of isoniazid and streptomycin that is associated with higher relapse rates. As early as 2 weeks, the more sterilizing regimen significantly reduced the volume of lung disease by computed tomography (P = 0.035) and also significantly reduced uptake of [F-18]-2-fluoro-2-deoxyglucose by positron emission tomography (P = 0.049). After 6 weeks of therapy, both treatments caused similar reductions in granuloma bacterial load, but the more sterilizing, four-drug regimen caused greater reduction in bacterial load in cavitary lesions (P = 0.009). These findings, combined with the association in humans between cavitary disease and relapse, suggest that the basis for improved sterilizing activity of the four-drug combination is both its faster disease volume resolution and its stronger sterilizing effect on cavitary lesions. Definitive data from relapse experiments are needed to support this observation.
C1 [Via, Laura E.; England, Kathleen; Weiner, Danielle M.; Schimel, Daniel; Dayao, Emmanuel; Chen, Ray Y.; Richardson, Mike; Robbins, Katherine K.; Cai, Ying; Barry, Clifton E., III] NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Zimmerman, Matthew D.; Dartois, Veronique] Rutgers State Univ, New Jersey Med Sch, Publ Hlth Res Inst, Newark, NJ 07102 USA.
[Dodd, Lori E.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
[Hammoud, Dima] NIH, Ctr Infect Dis Imaging Radiol & Imaging Sci, Bethesda, MD 20892 USA.
[Herscovitch, Peter] NIH, Positron Emiss Tomog Dept, Div Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA.
[Flynn, JoAnne L.] Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA USA.
[Barry, Clifton E., III] Univ Cape Town, Inst Infect Dis & Mol Med, Dept Clin Lab Sci, ZA-7925 Cape Town, South Africa.
RP Barry, CE (reprint author), NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM cbarry@niaid.nih.gov
RI Barry, III, Clifton/H-3839-2012;
OI Chen, Ray/0000-0001-6344-1442
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health; Bill & Melinda Gates
Foundation
FX This work was partially supported by the Intramural Research Program of
the National Institute of Allergy and Infectious Diseases, National
Institutes of Health, and the Bill & Melinda Gates Foundation TB Drug
Accelerator program (principal investigator [PI], JoAnne Flynn,
University of Pittsburgh).
NR 49
TC 6
Z9 6
U1 2
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
EI 1098-6596
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD JUL
PY 2015
VL 59
IS 7
BP 4181
EP 4189
DI 10.1128/AAC.00115-15
PG 9
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA CQ8YF
UT WOS:000360896000059
PM 25941223
ER
PT J
AU Ruggiero, FM
Vilcaes, AA
Iglesias-Bartolome, R
Daniotti, JL
AF Ruggiero, Fernando M.
Vilcaes, Aldo A.
Iglesias-Bartolome, Ramiro
Daniotti, Jose L.
TI Critical role of evolutionarily conserved glycosylation at Asn(211) in
the intracellular trafficking and activity of sialyltransferase
ST3Gal-II
SO BIOCHEMICAL JOURNAL
LA English
DT Article
DE ganglioside; glycolipid; Golgi complex; N-glycan trimming;
N-glycosylation; sialyltransferase; ST3Gal-II
ID GOLGI N-GLYCOSYLTRANSFERASES; PLASMA-MEMBRANE; ENZYME-ACTIVITY; GD3
SYNTHASE; CELL FUNCTIONS; CHO-K1 CELLS; MOUSE-BRAIN; EXPRESSION;
GANGLIOSIDES; COMPLEXES
AB ST3Gal-II, a type II transmembrane protein, is the main mammalian sialyltransferase responsible for GD1a and GT1b ganglioside biosynthesis in brain. It contains two putative N-glycosylation sites (Asn(92) and Asn(211)). Whereas Asn(92) is only conserved in mammalian species, Asn(211) is highly conserved in mammals, birds and fish. The present study explores the occupancy and relevance for intracellular trafficking and enzyme activity of these potential N-glycosylations in human ST3Gal-II. We found that ST3Gal-II distributes along the Golgi complex, mainly in proximal compartments. By pharmacological, biochemical and site-directed mutagenesis, we observed that ST3Gal-II is mostly N-glycosylated at Asn(211) and that this co-translational modification is critical for its exit from the endoplasmic reticulum and proper Golgi localization. The individual N-glycosylation sites had different effects on ST3Gal-II enzymatic activity. Whereas the N-glycan at position Asn(211) seems to negatively influence the activity of the enzyme using both glycolipid and glycoprotein as acceptor substrates, the single N-glycan mutant at Asn(92) had only a moderate effect. Lastly, we demonstrated that the N-terminal ST3Gal-II domain containing the cytosolic, transmembrane and stem region (amino acids 1-51) is able to drive a protein reporter out of the endoplasmic reticulum and to retain it in the Golgi complex. This suggests that the C-terminal domain of ST3Gal-II depends on N-glycosylation to attain an optimum conformation for proper exit from the endoplasmic reticulum, but it does not represent an absolute requirement for Golgi complex retention of the enzyme.
C1 [Ruggiero, Fernando M.; Vilcaes, Aldo A.; Daniotti, Jose L.] Univ Nacl Cordoba, Fac Ciencias Quim, Dept Quim Biol, Ctr Invest Quim Biol Cordoba,CIQUIBIC,UNC CONICET, RA-5000 Cordoba, Argentina.
[Iglesias-Bartolome, Ramiro] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
RP Daniotti, JL (reprint author), Univ Nacl Cordoba, Fac Ciencias Quim, Dept Quim Biol, Ctr Invest Quim Biol Cordoba,CIQUIBIC,UNC CONICET, RA-5000 Cordoba, Argentina.
EM daniotti@dqb.fcq.unc.edu.ar
FU Secretaria de Ciencia y Tecnologia (SECyT) [203/14]; Universidad
Nacional de Cordoba (UNC); Consejo Nacional de Investigaciones
Cientificas y Tecnicas (CONICET) [PIP 112-20110100930]; Agencia Nacional
de Promocion Cientifica y Tecnologica (ANPCyT, PICT), Argentina [1487,
456]; ANPCyT; CONICET
FX This work was supported in part by the Secretaria de Ciencia y
Tecnologia (SECyT, 203/14), Universidad Nacional de Cordoba (UNC),
Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET, PIP
112-20110100930) and Agencia Nacional de Promocion Cientifica y
Tecnologica (ANPCyT, PICT 2010 No 1487, PICT 2013 No 456), Argentina.
F.M.R. is a recipient of an ANPCyT and CONICET fellowship. A.A.V. and
J.L.D. are career investigators of CONICET (Argentina).
NR 53
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U1 0
U2 1
PU PORTLAND PRESS LTD
PI LONDON
PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND
SN 0264-6021
EI 1470-8728
J9 BIOCHEM J
JI Biochem. J.
PD JUL 1
PY 2015
VL 469
BP 83
EP 95
DI 10.1042/BJ20150072
PN 1
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CR0YX
UT WOS:000361050900009
PM 25916169
ER
PT J
AU Bridge, JA
Asti, L
Horowitz, LM
Greenhouse, JB
Fontanella, CA
Sheftall, AH
Kelleher, KJ
Campo, JV
AF Bridge, Jeffrey A.
Asti, Lindsey
Horowitz, Lisa M.
Greenhouse, Joel B.
Fontanella, Cynthia A.
Sheftall, Arielle H.
Kelleher, Kelly J.
Campo, John V.
TI Suicide Trends Among Elementary School-Aged Children in the United
States From 1993 to 2012
SO JAMA PEDIATRICS
LA English
DT Article
ID ADOLESCENT SUICIDE; VIOLENCE; YOUTHS; MISCLASSIFICATION; INTERVENTIONS;
DISPARITIES; PREVENTION; EXPOSURE; BEHAVIOR
AB IMPORTANCE Suicide is a leading cause of death among school-aged children younger than 12 years but little is known about the epidemiology of suicide in this age group.
OBJECTIVE To describe trends in suicide among US children younger than 12 years by sociodemographic group and method of death.
DESIGN, SETTING, AND PARTICIPANTS Period trend analysis of national mortality data on suicide in children aged 5 to 11 years in the United States from January 1, 1993, to December 31, 2012. Data were analyzed per 5-year periods, between 1993 to 1997 and 2008 to 2012.
MAIN OUTCOMES AND MEASURES Number of suicide deaths and crude suicide rates. Period trends in rates of suicide were estimated using negative binomial regression incidence rate ratios (IRRs).
RESULTS The overall suicide rate among children aged 5 toll years remained stable between 1(-393 to 1997 and 2008 to 2012 (from 1.18 to 1.09 per lmillion; IRR = 0.96; 95% Cl, 0.90-1.03). However, the suicide rate increased significantly in black children (from 1.36 to 2.54 per 1 million; IRR = 1.27; 95% Cl, 1.11-1.45) and decreased in white children (from 1.14 to 0.77 per 1 million; IRR = 0.86; 95% Cl. 0.79-0.94). The overall firearm suicide rate (IRR = 0.69; 95% Cl. 0.57-0.85) and firearm suicide rate among white boys (IRR = 0.72; 95% Cl, 0.59-0.88) decreased significantly during the study. The rate of suicide by hanging/suffocation increased significantly in black boys (IRR = 1.35; 95% Cl, 1.14-1.61), although the overall change in suicide rates by hanging/suffocation or other suicide methods did not change during the study.
CONCLUSIONS AND RELEVANCE The stable overall suicide rate in school-aged children in the United States during 20 years of study obscured a significant increase in suicide incidence in black children and a significant decrease in suicide incidence among white children. Findings highlight a potential racial disparity that warrants attention. Further studies are needed to monitor these emerging trends and identify risk, protective, and precipitating factors relevant to suicide prevention efforts in children younger than 12 years.
C1 [Bridge, Jeffrey A.; Asti, Lindsey; Sheftall, Arielle H.; Kelleher, Kelly J.] Nationwide Childrens Hosp, Res Inst, Columbus, OH 43205 USA.
[Bridge, Jeffrey A.; Kelleher, Kelly J.] Ohio State Univ, Coll Med, Dept Pediat, Columbus, OH 43210 USA.
[Horowitz, Lisa M.] NIMH, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Greenhouse, Joel B.] Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA.
[Fontanella, Cynthia A.; Campo, John V.] Ohio State Univ, Coll Med, Dept Psychiat, Columbus, OH 43210 USA.
RP Bridge, JA (reprint author), Nationwide Childrens Hosp, Res Inst, Ctr Innovat Pediat Practice, 700 Childrens Dr, Columbus, OH 43205 USA.
EM jeff.bridge@nationwidechildrens.org
FU National Institute of Mental Health, National Institutes of Health
[R01-MH093552]; Centers for Disease Control and Prevention
[R01-CE002129]
FX Dr Bridge was supported by grant R01-MH093552 from the National
Institute of Mental Health, National Institutes of Health, and grant
R01-CE002129 from the Centers for Disease Control and Prevention.
NR 33
TC 15
Z9 15
U1 1
U2 15
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6203
EI 2168-6211
J9 JAMA PEDIATR
JI JAMA Pediatr.
PD JUL
PY 2015
VL 169
IS 7
BP 673
EP 677
DI 10.1001/jamapediatrics.2015.0465
PG 5
WC Pediatrics
SC Pediatrics
GA CR0BF
UT WOS:000360982500015
PM 25984947
ER
PT J
AU Harskamp-van Ginkel, MW
Hill, KD
Becker, K
Testoni, D
Cohen-Wolkowiez, M
Gonzalez, D
Barrett, JS
Benjamin, DK
Siegel, DA
Banks, P
Watt, KM
AF Harskamp-van Ginkel, Margreet W.
Hill, Kevin D.
Becker, Kristian
Testoni, Daniela
Cohen-Wolkowiez, Michael
Gonzalez, Daniel
Barrett, Jeffrey S.
Benjamin, Daniel K., Jr.
Siegel, David A.
Banks, Patricia
Watt, Kevin M.
CA Best Pharmaceuticals Children
TI Drug Dosing and Pharmacokinetics in Children With Obesity A Systematic
Review
SO JAMA PEDIATRICS
LA English
DT Review
ID DISPOSITION CLASSIFICATION-SYSTEM; ACUTE LYMPHOBLASTIC-LEUKEMIA; CHRONIC
KIDNEY-DISEASE; SERUM CONCENTRATIONS; PEDIATRIC-PATIENTS; NORMAL-WEIGHT;
BODY-MASS; OVERWEIGHT; CARBAMAZEPINE; ADOLESCENTS
AB IMPORTANCE Obesity affects nearly one-sixth of US children and results in alterations to body composition and physiology that can affect drug disposition, possibly leading to therapeutic failure or toxic side effects. The depth of available literature regarding obesity's effect on drug safety, pharmacokinetics, and dosing in obese children is unknown.
OBJECTIVE To perform a systematic literature review describing the current evidence of the effect oF obesity on drug disposition in children.
EVIDENCE REVIEW We searched the MEDLINE. Cochrane, and EMBASE databases (January 1, 1970-December 31, 2012) and included studies if they contained data on drug clearance, volume of distribution, or drug concentration in obese children (aged <= 18 years). We compared exposure and weight-normalized volume of distribution and clearance between obese and nonobese children. We explored the association between drug physicochemical properties and clearance and volume of distribution.
FINDINGS Twenty studies met the inclusion criteria and contained pharmacokinetic data for 21 drugs. The median number of obese children studied per drug was 10 (range, 1-112) and ages ranged from newborn to 29 years (1 study described pharmacokinetics in children and adults together). Dosing schema varied and were either a fixed dose (6 [29%]) or based on body weight (10 [48%]) and body surface area (4 [19%]). Clinically significant pharmacokinetic alterations were observed in obese children for 65% (11 of 17) of the studied drugs. Pharmacokinetic alterations resulted in substantial differences in exposure between obese and nonobese children for 38% (5 of 13) of the drugs. We found no association between drug lipophilicity or Biopharmaceutical Drug Disposition Classification System class and changes in volume of distribution or clearance due to obesity.
CONCLUSIONS AND RELEVANCE Consensus is lacking on the most appropriate weight-based dosing strategy for obese children. Prospective pharmacokinetic trials in obese children are needed to ensure therapeutic efficacy and enhance drug safety.
C1 [Harskamp-van Ginkel, Margreet W.; Hill, Kevin D.; Becker, Kristian; Testoni, Daniela; Cohen-Wolkowiez, Michael; Gonzalez, Daniel; Benjamin, Daniel K., Jr.; Banks, Patricia; Watt, Kevin M.] Duke Univ, Dept Pediat, Durham, NC 27706 USA.
[Harskamp-van Ginkel, Margreet W.; Hill, Kevin D.; Becker, Kristian; Testoni, Daniela; Cohen-Wolkowiez, Michael; Gonzalez, Daniel; Benjamin, Daniel K., Jr.; Banks, Patricia; Watt, Kevin M.] Duke Univ, Duke Clin Res Inst, Durham, NC USA.
[Harskamp-van Ginkel, Margreet W.] Univ Amsterdam, Acad Med Ctr, Dept Publ Hlth, NL-1105 AZ Amsterdam, Netherlands.
[Gonzalez, Daniel] Univ N Carolina, Eshelman Sch Pharm, Div Pharmacotherapy & Expt Therapeut, Chapel Hill, NC USA.
[Barrett, Jeffrey S.] Childrens Hosp Philadelphia, Dept Clin Pharmacol & Therapeut, Philadelphia, PA 19104 USA.
[Siegel, David A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Benjamin, DK (reprint author), Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27705 USA.
EM danny.benjamin@duke.edu
FU National Institute of Child Health and Human Development (NICHD)
[HHSN2752010000031]; National Center for Advancing Translational
Sciences of the National Institutes of Health [UL1TR001117]; National
Institutes of Health (NIH) [1K23HD064814]; National Center for Advancing
Translational Sciences of the NIH [UL1TR001117]; US Food and Drug
Administration [1U01FD004858-01]; Biomedical Advanced Research and
Development Authority [HHS0100201300009C]; Thrasher Research Fund;
industry for drug development in adults and children; National Institute
of General Medical Sciences [T32GM086330, 1T32GM086330-01A1]; NICHD from
the US government [HHSN2752010000031]; [1R01HD057956-05];
[1K24HD058735-05]
FX This work was funded under National Institute of Child Health and Human
Development (NICHD) contract HHSN2752010000031 for the Pediatric Trials
Network. Research reported in this publication was also supported by
award number UL1TR001117 from the National Center for Advancing
Translational Sciences of the National Institutes of Health. Dr
Cohen-Wolkowiez reported receiving grant 1K23HD064814 for research from
the National Institutes of Health (NIH), award number UL1TR001117 from
the National Center for Advancing Translational Sciences of the NIH,
grant 1U01FD004858-01 from the US Food and Drug Administration, and
grant HHS0100201300009C from the Biomedical Advanced Research and
Development Authority, as well as support from the Thrasher Research
Fund (http://www.thrasherresearch.org) and from industry for drug
development in adults and children
(http://www.dcri.duke.edu/research/coi.jsp). Dr Gonzalez reported
receiving training grant T32GM086330 from the National Institute of
General Medical Sciences, Dr Benjamin reported receiving grants
1R01HD057956-05, 1K24HD058735-05, and UL1TR001117 and NICHD contract
HHSN2752010000031 from the US government for his work in pediatric and
neonatal clinical pharmacology as well as support from the Thrasher
Research Fund for his work in neonatal candidiasis and from industry for
neonatal and pediatric drug development
(http://www.dcri.duke.edu/research/coi.jsp). Dr Watt reported receiving
grant 1T32GM086330-01A1 from the National Institute of General Medical
Sciences and support from the Thrasher Research Fund for his work in
pediatric clinical pharmacology.
NR 53
TC 9
Z9 9
U1 3
U2 9
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6203
EI 2168-6211
J9 JAMA PEDIATR
JI JAMA Pediatr.
PD JUL
PY 2015
VL 169
IS 7
BP 678
EP 685
DI 10.1001/jamapediatrics.2015.132
PG 8
WC Pediatrics
SC Pediatrics
GA CR0BF
UT WOS:000360982500016
PM 25961828
ER
PT J
AU Guevara-Aguirre, J
Rosenbloom, AL
Balasubramanian, P
Teran, E
Guevara-Aguirre, M
Guevara, C
Procel, P
Alfaras, I
De Cabo, R
Di Biase, S
Narvaez, L
Saavedra, J
Longo, VD
AF Guevara-Aguirre, Jaime
Rosenbloom, Arlan L.
Balasubramanian, Priya
Teran, Enrique
Guevara-Aguirre, Marco
Guevara, Carolina
Procel, Patricio
Alfaras, Irene
De Cabo, Rafael
Di Biase, Stefano
Narvaez, Luis
Saavedra, Jannette
Longo, Valter D.
TI GH Receptor Deficiency in Ecuadorian Adults Is Associated With Obesity
and Enhanced Insulin Sensitivity
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID PRADER-WILLI-SYNDROME; GROWTH-HORMONE DEFICIENCY; LARON-SYNDROME;
ADIPONECTIN LEVELS; DIABETES-MELLITUS; CHILDREN; LEPTIN; METABOLISM;
PHENOTYPE; RISK
AB Context: Ecuadorian subjects with GH receptor deficiency (GHRD) have not developed diabetes, despite obesity. Objective: We sought to determine the metabolic associations for this phenomenon.
Design: Four studies were carried out: 1) glucose, lipid, adipocytokine concentrations; 2) metabolomics evaluation; 3) metabolic responses to a high-calorie meal; and 4) oral glucose tolerance tests.
Setting: Clinical Research Institute in Quito, Ecuador.
Subjects: Adults homozygous for the E180 splice mutation of the GH receptor (GHRD) were matched for age, gender, and body mass index with unaffected control relatives (C) as follows: study 1, 27 GHRD and 35 C; study 2, 10 GHRD and 10 C; study 3, seven GHRD and 11 C; and study 4, seven GHRD and seven C.
Results: AlthoughGHRDsubjectshadgreatermeanpercentagebodyfatthancontrols, theirfastinginsulin, 2-hour blood glucose, and triglyceride levels were lower. The indicator of insulin sensitivity, homeostasis model of assessment 2% S, was greater (P < .0001), and the indicator of insulin resistance, homeostasis model of assessment 2-IR, was lower (P = .0025). Metabolomic differences between GHRD and control subjects were consistent with their differing insulin sensitivity, including postprandial decreases of branched-chain amino acids that were more pronounced in controls. High molecular weight and total adiponectin concentrations were greater inGHRD(P = .0004 and P = .0128, respectively), and leptin levels were lower (P = .02). Although approximately 65% the weight of controls, GHRD subjects consumed an identical high-calorie meal; nonetheless, theirmeanglucose concentrationswerelower, withmeaninsulin levels one-third those of controls. Results of the 2-hour oral glucose tolerance test were similar. Main Outcome Measures: Measures of insulin sensitivity, adipocytokines, and energy metabolites.
Conclusions: WithoutGHcounter-regulation, GHRDisassociatedwithinsulinefficiencyandobesity. Lower leptin levels, despite higher percentage body fat, suggest that obesity-associated leptin resistance is GH dependent. Elevated adiponect in levels not correlated with percentage body fat indicate that GH signaling is necessary for their typical suppression with obesity.
C1 [Guevara-Aguirre, Jaime; Teran, Enrique] USFQ, Quito, Ecuador.
[Guevara-Aguirre, Jaime; Rosenbloom, Arlan L.; Guevara-Aguirre, Marco; Guevara, Carolina; Procel, Patricio; Narvaez, Luis; Saavedra, Jannette] Inst Endocrinol Metab & Reprod, Quito, Ecuador.
[Rosenbloom, Arlan L.] Univ Florida, Coll Med, Gainesville, FL 32608 USA.
[Balasubramanian, Priya; Di Biase, Stefano; Longo, Valter D.] Univ So Calif, Davis Sch Gerontol, Los Angeles, CA 90089 USA.
[Alfaras, Irene; De Cabo, Rafael] NIA, Expt Gerontol Sect, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA.
[Longo, Valter D.] Univ So Calif, Longev Inst, Los Angeles, CA 90089 USA.
RP Guevara-Aguirre, J (reprint author), USFQ, Av Diego de Robles & Pampite, Cumbaya Quito, Ecuador.
EM guevaraaguirre@yahoo.com; vlongo@usc.edu
RI de Cabo, Rafael/J-5230-2016; Teran, Enrique/L-6000-2016;
OI de Cabo, Rafael/0000-0002-3354-2442; Teran, Enrique/0000-0001-6979-5655;
, rafael/0000-0003-2830-5693
FU Instituto de Endocrinologia, Metabolismo y Reproduccion (IEMYR);
Universidad San Francisco de Quito USFQ, Ecuador; Intramural Research
Program of the National Institutes of Health/National Institute on
Aging; University of Southern California Edna Jones Chair; National
Geographic Research Grant; Fundacion Alonso Martin Escudero
FX This work was supported by Instituto de Endocrinologia, Metabolismo y
Reproduccion (IEMYR) and Universidad San Francisco de Quito USFQ,
Ecuador; the Intramural Research Program of the National Institutes of
Health/ National Institute on Aging; the University of Southern
California Edna Jones Chair (to V. D. L.); The National Geographic
Research Grant; and the Fundacion Alonso Martin Escudero (to I. A.).
NR 31
TC 8
Z9 8
U1 1
U2 5
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD JUL
PY 2015
VL 100
IS 7
BP 2589
EP 2596
DI 10.1210/jc.2015-1678
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CQ8EZ
UT WOS:000360840600029
PM 25985182
ER
PT J
AU Perez-Rivas, LG
Theodoropoulou, M
Ferrau, F
Nusser, C
Kawaguchi, K
Stratakis, CA
Faucz, FR
Wildemberg, LE
Assie, G
Beschorner, R
Dimopoulou, C
Buchfelder, M
Popovic, V
Berr, CM
Toth, M
Ardisasmita, AI
Honegger, J
Bertherat, J
Gadelha, MR
Beuschlein, F
Stalla, G
Komada, M
Korbonits, M
Reincke, M
AF Perez-Rivas, Luis G.
Theodoropoulou, Marily
Ferrau, Francesco
Nusser, Clara
Kawaguchi, Kohei
Stratakis, Constantine A.
Faucz, Fabio Rueda
Wildemberg, Luiz E.
Assie, Guillaume
Beschorner, Rudi
Dimopoulou, Christina
Buchfelder, Michael
Popovic, Vera
Berr, Christina M.
Toth, Miklos
Ardisasmita, Arif Ibrahim
Honegger, Juergen
Bertherat, Jerome
Gadelha, Monica R.
Beuschlein, Felix
Stalla, Guenter
Komada, Masayuki
Korbonits, Mrta
Reincke, Martin
TI The Gene of the Ubiquitin-Specific Protease 8 Is Frequently Mutated in
Adenomas Causing Cushing's Disease
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID CORTICOTROPIN-SECRETING TUMORS; LONG-TERM REMISSION; GROWTH-FACTOR
RECEPTOR; HUMAN PITUITARY-TUMORS; TRANSSPHENOIDAL SURGERY;
SINGLE-CENTER; RECURRENCE RATES; EXPRESSION; ALPHA; MUTATIONS
AB Context: We have recently reported somatic mutations in the ubiquitin-specific protease USP8 gene in a small series of adenomas of patients with Cushing's disease.
Objective: To determine the prevalence of USP8 mutations and the genotype-phenotype correlation in a large series of patients diagnosed with Cushing's disease.
Design: We performed a retrospective, multicentric, genetic analysis of 134 functioning and 11 silent corticotroph adenomas using Sanger sequencing. Biochemical and clinical features were collected and examined within the context of the mutational status of USP8, and new mutations were characterized by functional studies.
Patients: A total of 145 patients who underwent surgery for an ACTH-producing pituitary adenoma.
Main Outcomes Measures: Mutational status of USP8. Biochemical and clinical features included sex, age at diagnosis, tumor size, preoperative and postoperative hormonal levels, and comorbidities.
Results: We found somatic mutations in USP8 in 48 (36%) pituitary adenomas from patients with Cushing's disease but in none of 11 silent corticotropinomas. The prevalence was higher in adults than in pediatric cases (41 vs 17%) and in females than in males (43 vs 17%). Adults having USP8mutated adenomas were diagnosed at an earlier age than those with wild-type lesions (36 vs 44 y). Mutations were primarily found in adenomas of 10 +/- 7mmand were inversely associated with the developmentof postoperative adrenal insufficiency. All the mutations affected the residues Ser718 or Pro720, including five new identified alterations. Mutations reduced the interaction between USP8 and 14-3-3 and enhanced USP8 activity. USP8 mutants diminished epidermal growth factor receptor ubiquitination and induced Pomc promoter activity in immortalized AtT-20 corticotropinoma cells.
Conclusions: USP8 is frequently mutated in adenomas causing Cushing's disease, especially in those from female adult patients diagnosed at a younger age.
C1 [Perez-Rivas, Luis G.; Nusser, Clara; Berr, Christina M.; Beuschlein, Felix; Reincke, Martin] Univ Munich, Med Klin & Poliklin 4, D-80336 Munich, Germany.
[Theodoropoulou, Marily; Dimopoulou, Christina; Stalla, Guenter] Max Planck Inst Psychiat, Dept Endocrinol, D-80804 Munich, Germany.
[Ferrau, Francesco; Korbonits, Mrta] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, Ctr Endocrinol, London EC1M 6BQ, England.
[Kawaguchi, Kohei; Ardisasmita, Arif Ibrahim; Komada, Masayuki] Tokyo Inst Technol, Grad Sch Biosci & Biotechnol, Dept Biol Sci, Midori Ku, Yokohama, Kanagawa 2268501, Japan.
[Stratakis, Constantine A.; Faucz, Fabio Rueda] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
[Wildemberg, Luiz E.; Gadelha, Monica R.] Univ Fed Rio de Janeiro, Hosp Univ Clementino Fraga Filho, Div Endocrinol, BR-21941913 Rio De Janeiro, Brazil.
[Assie, Guillaume; Bertherat, Jerome] Univ Paris 05, INSERM, U1016, CNRS,UMR,Inst Cochin, F-75014 Paris, France.
[Beschorner, Rudi] Univ Tubingen, Dept Neuropathol, Inst Pathol & Neuropathol, D-72076 Tubingen, Germany.
[Buchfelder, Michael] Univ Erlangen Nurnberg, Klinikum Univ Erlangen, Neurochirurg Klin, D-91054 Erlangen, Germany.
[Honegger, Juergen] Univ Tubingen, Dept Neurosurg, D-72076 Tubingen, Germany.
[Popovic, Vera] Univ Belgrade, Fac Med, Belgrade 11000, Serbia.
Univ Belgrade, Univ Clin Ctr, Clin Endocrinol Diabet & Metab Dis, Belgrade 11000, Serbia.
[Toth, Miklos] Semmelweis Univ, Fac Med, Dept Med 2, H-1088 Budapest, Hungary.
[Ardisasmita, Arif Ibrahim] Bandung Inst Technol, Sch Life Sci & Technol, Bandung 40132, Indonesia.
RP Reincke, M (reprint author), Klinikum Univ Munchen, Med Klin & Poliklin 4, Ziemssenstr 1, D-80336 Munich, Germany.
EM martin.reincke@med.uni-muenchen.de
RI Ferrao, Francesco/P-8852-2015;
OI Ferrao, Francesco/0000-0002-7472-6598; Korbonits,
Marta/0000-0002-4101-9432
FU Else Kroner-Fresenius-Stiftung [2012_A103]; Ministry of Education,
Culture, Science and Technology of Japan [24112003]; German Research
Foundation [RE 752/20-1]; German Federal Ministry of Education and
Research [01EX1021B]; People Programme (Marie Curie Actions) of the
European Union's Seventh Framework Programme (FP7) [608765]; intramural
research program of the National Institute of Child Health and Human
Development, National Institutes of Health; Pfizer
FX The study was supported by the Else Kroner-Fresenius-Stiftung (Grant
2012_A103; to M.R.) and Grants-in-aid from the Ministry of Education,
Culture, Science and Technology of Japan (Grant 24112003; to M.Kom.).
L.G.P.-R. is supported by a grant from the German Research Foundation
(Grant RE 752/20-1). M. The. is supported by a grant from the German
Federal Ministry of Education and Research (01EX1021B, Spitzencluster
M4, Verbund Personalisierte Medizin, Teilprojekt NeoExNET [PM1]). The
research leading to these results has received funding from the People
Programme (Marie Curie Actions) of the European Union's Seventh
Framework Programme (FP7/2007-2013) under REA grant agreement no. 608765
and was also, in part, supported by the intramural research program of
the National Institute of Child Health and Human Development, National
Institutes of Health (to C.A.S.) and by a research grant by Pfizer (to
M. Kor.). L.G.P.-R. and M.R. had full access to all of the data in the
study and take responsibility for the integrity of the data and the
accuracy of the data analysis. The funder institutions had no role in
the design and conduct of the study; collection, management, analysis,
and interpretation of the data; preparation, review, or approval of the
manuscript; or the decision to submit the manuscript for publication.
NR 37
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U1 2
U2 10
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD JUL
PY 2015
VL 100
IS 7
BP E997
EP E1004
DI 10.1210/jc.2015-1453
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CQ8EZ
UT WOS:000360840600007
PM 25942478
ER
PT J
AU Roberts, KK
Hill, TE
Dayis, MN
Holbrook, MR
Freiberg, AN
AF Roberts, Kimberly K.
Hill, Terence E.
Dayis, Melissa N.
Holbrook, Michael R.
Freiberg, Alexander N.
TI Cytokine response in mouse bone marrow derived macrophages after
infection with pathogenic and non-pathogenic Rift Valley fever virus
SO JOURNAL OF GENERAL VIROLOGY
LA English
DT Article
ID RAW 264.7 CELLS; INTERFERON-GAMMA; INFLAMMATORY RESPONSES;
RHESUS-MONKEYS; PROTEIN-KINASE; ACTIVATION; AFRICA; NSS; TRANSCRIPTION;
MECHANISMS
AB Rift Valley fever virus (RVFV) is the most pathogenic member of the genus Phlebovirus within the family Bunyaviridae, and can cause severe disease in humans and livestock. Until recently, limited information has been published on the cellular host response elicited by RVFV, particularly in macrophages and dendritic cells, which play critical roles in stimulating adaptive and innate immune responses to viral infection. In an effort to define the initial response of host immunomodulatory cells to infection, primary mouse bone marrow derived macrophages (BMDM) were infected with the pathogenic RVFV strain ZH501, or attenuated strains MP-12 or MP-12 based Clone13 type (rMP12-C13 type), and cytokine secretion profiles examined. The secretion of T helper (Th)1-associated antiviral cytokines, chemokines and various interleukins increased rapidly after infection with the attenuated rMP12-C13 type RVFV, which lacks a functional NSs virulence gene. In comparison, infection with live-attenuated MP-12 encoding a functional NSs gene appeared to cause a delayed immune response, while pathogenic ZH501 ablates the immune response almost entirely. These data demonstrate that NSs can inhibit components of the BMDM antiviral response and supports previous work indicating that NSs can specifically regulate the type I interferon response in macrophages. Furthermore, our data demonstrate that genetic differences between ZH501 and MP-12 reduce the ability of MP-12 to inhibit antiviral signalling and subsequently reduce virulence in BMDM, demonstrating that viral components other than NSs play a critical role in regulating the host response to RVFV infection.
C1 [Roberts, Kimberly K.; Hill, Terence E.; Holbrook, Michael R.; Freiberg, Alexander N.] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA.
[Dayis, Melissa N.; Holbrook, Michael R.] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA.
[Holbrook, Michael R.; Freiberg, Alexander N.] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA.
[Holbrook, Michael R.; Freiberg, Alexander N.] Univ Texas Med Branch, Inst Human Infect & Immun, Galveston, TX 77555 USA.
[Holbrook, Michael R.; Freiberg, Alexander N.] Univ Texas Med Branch, Ctr Trop Dis, Galveston, TX 77555 USA.
[Holbrook, Michael R.] NIAID, Integrated Res Facil, NIH, Frederick, MD USA.
RP Freiberg, AN (reprint author), Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA.
EM anfreibe@utmb.edu
FU UTMB; Ruth L. Kirschstein National Research Service Award at UTMB
[AI080162-01A1]; Battelle Memorial Institute; US National Institute of
Allergy and Infectious Diseases (NIAID) [HHSN272200700016I]
FX This work was partially supported by start-up funds (UTMB) to A. N. F.
K. K. R. was partially supported by the Ruth L. Kirschstein National
Research Service Award (AI080162-01A1) at UTMB. M. R. H. was partially
supported through Battelle Memorial Institute's prime contract with the
US National Institute of Allergy and Infectious Diseases (NIAID) under
contract no. HHSN272200700016I. K. K. R. would like to thank Dr Bersabeh
Tigabu (UTMB) for providing training on the isolation and cultivation of
mouse primary macrophages. The content of this publication does not
necessarily reflect the views or policies of the US Department of Health
and Human Services (DHHS) or of the institutions or companies affiliated
with the authors.
NR 59
TC 4
Z9 4
U1 0
U2 2
PU SOC GENERAL MICROBIOLOGY
PI READING
PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG,
BERKS, ENGLAND
SN 0022-1317
EI 1465-2099
J9 J GEN VIROL
JI J. Gen. Virol.
PD JUL
PY 2015
VL 96
BP 1651
EP 1663
DI 10.1099/vir.0.000119
PN 7
PG 13
WC Biotechnology & Applied Microbiology; Virology
SC Biotechnology & Applied Microbiology; Virology
GA CQ8QB
UT WOS:000360872400014
PM 25759029
ER
PT J
AU Dreja, H
Pade, C
Chen, L
McKnight, A
AF Dreja, Hanna
Pade, Corinna
Chen, Lei
McKnight, Aine
TI CD4 binding site broadly neutralizing antibody selection of HIV-1 escape
mutants
SO JOURNAL OF GENERAL VIROLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODIES; FAB
FRAGMENTS; GP120; TYPE-1; POTENT; IMMUNIZATION; INDIVIDUALS; RESPONSES;
SEQUENCE
AB All human immunodeficiency virus type-1 (HIV-1) viruses use CD4 to enter cells. Consequently, the viral envelope CD4-binding site (CD4bs) is relatively conserved, making it a logical neutralizing antibody target. It is important to understand how CD4-binding site variation allows for escape from neutralizing antibodies. Alanine scanning mutagenesis identifies residues in antigenic sites, whereas escape mutant selection identifies viable mutants. We selected HIV-1 to escape CD4bs neutralizing mAbs b12, A12 and HJ16. Viruses that escape from Al 2 and b12 remained susceptible to HJ16, VRC01 and J3, whilst six different viruses that escape HJ16 remained sensitive to A12, b12 and J3. In contrast, their sensitivity to VRC01 was variable. Triple HJ16/A12/b12-resistant virus proved that HIV-1 could escape multiple broadly neutralizing monoclonal antibodies, but still retain sensitivity to VRC01 and the llama-derived J3 nanobody. This antigenic variability may reflect that occurring in circulating viruses, so studies like this can predict immunologically relevant antigenic forms of the CD4bs for inclusion in HIV-1 vaccines.
C1 [Dreja, Hanna; Pade, Corinna; McKnight, Aine] Queen Mary Univ London, Balls & London Sch Med & Dent, Blizard Inst, Ctr Immunol & Infect Dis, London, England.
[Chen, Lei] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP McKnight, A (reprint author), Queen Mary Univ London, Balls & London Sch Med & Dent, Blizard Inst, Ctr Immunol & Infect Dis, London, England.
EM a.mcknight@qmul.ac.uk
FU Bill and Melinda Gates Foundation (Weiss VDAC, UCL)
FX B12 was provided by Dennis Burton, The Scripps Research Institute; A12
and J3 from Robin Weiss, UCL; HJ16 from Humabs Biomed SA, Switzerland.
VRC01 was obtained through the AIDS Research and Reference Reagent
Program, Division of AIDS, NIAID, NIH, from John Mascola and CD4-IgG2
through the NIH AIDS Reagent Program, Division of AIDS, MAID, NIH:
Cat#11780 from Progenics Pharmaceuticals. The genetic replication
competent clone HXB2 was obtained from the Centre for AIDS Research
(NIBSC, UK). Plasmid psvIII-HXB2 was provided by Paul Clapham,
Worcester, MA. This research was conducted as part of the Collaboration
for AIDS Vaccine Discovery funded by the Bill and Melinda Gates
Foundation (Weiss VDAC, UCL). We would like to thank Robin Weiss, Peter
Kwong and Laura McCoy for critically reading the manuscript.
NR 26
TC 2
Z9 2
U1 0
U2 0
PU SOC GENERAL MICROBIOLOGY
PI READING
PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG,
BERKS, ENGLAND
SN 0022-1317
EI 1465-2099
J9 J GEN VIROL
JI J. Gen. Virol.
PD JUL
PY 2015
VL 96
BP 1899
EP 1905
DI 10.1099/vir.0.000120
PN 7
PG 7
WC Biotechnology & Applied Microbiology; Virology
SC Biotechnology & Applied Microbiology; Virology
GA CQ8QB
UT WOS:000360872400040
PM 25762593
ER
PT J
AU Frank, GM
Angeletti, D
Ince, WL
Gibbs, JS
Khurana, S
Wheatley, AK
Max, EE
McDermott, AB
Golding, H
Stevens, J
Bennink, JR
Yewdell, JW
AF Frank, Gregory M.
Angeletti, Davide
Ince, William L.
Gibbs, James S.
Khurana, Surender
Wheatley, Adam K.
Max, Edward E.
McDermott, Adrian B.
Golding, Hana
Stevens, James
Bennink, Jack R.
Yewdell, Jonathan W.
TI A Simple Flow-Cytometric Method Measuring B Cell Surface Immunoglobulin
Avidity Enables Characterization of Affinity Maturation to Influenza A
Virus
SO MBIO
LA English
DT Article
ID ANTIBODY-RESPONSE; IMMUNE-RESPONSE; PLASMA-CELLS; MEMORY; HEMAGGLUTININ;
INFECTION; ANTIGEN; EXPRESSION; RECEPTOR; VACCINES
AB Antibody (Ab) affinity maturation enables an individual to maintain immunity to an increasing number of pathogens within the limits of a total Ig production threshold. A better understanding of this process is critical for designing vaccines that generate optimal Ab responses to pathogens. Our study describes a simple flow-cytometric method that enumerates virus-specific germinal center (GC) B cells as well as their AC(50), a measure of Ab avidity, defined as the antigen concentration required to detect 50% of specific B cells. Using a model of mouse Ab responses to the influenza A virus hemagglutinin (IAV HA), we obtained data indicating that AC(50) decreases with time postinfection in an affinity maturation-dependent process. As proof of principle of the utility of the method, our data clearly show that relative to intranasal IAV infection, intramuscular immunization against inactivated IAV in adjuvant results in a diminished GC HA B cell response, with increased AC(50) correlating with an increased serum Ab off-rate. Enabling simultaneous interrogation of both GC HA B cell quantity and quality, this technique should facilitate study of affinity maturation and rational vaccine design.
IMPORTANCE Though it was first described 50 years ago, little is known about how antibody affinity maturation contributes to immunity. This question is particularly relevant to developing more effective vaccines for influenza A virus (IAV) and other viruses that are difficult vaccine targets. Limitations in methods for characterizing antigen-specific B cells have impeded progress in characterizing the quality of immune responses to vaccine and natural immunogens. In this work, we describe a simple flow cytometry-based approach that measures both the number and affinity of IAV-binding germinal center B cells specific for the IAV HA, the major target of IAV-neutralizing antibodies. Using this method, we showed that the route and form of immunization significantly impacts the quality and quantity of B cell antibody responses. This method provides a relatively simple yet powerful tool for better understanding the contribution of affinity maturation to viral immunity.
C1 [Frank, Gregory M.; Angeletti, Davide; Ince, William L.; Gibbs, James S.; Bennink, Jack R.; Yewdell, Jonathan W.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
[Khurana, Surender; Golding, Hana] US FDA, Ctr Biol Evaluat & Res, Silver Spring, MD USA.
[Wheatley, Adam K.; McDermott, Adrian B.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Max, Edward E.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
[Stevens, James] Ctr Dis Control & Prevent, Natl Ctr Immunizat & Resp Dis, Influenza Div, Atlanta, GA USA.
RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM jyewdell@mail.nih.gov
OI Wheatley, Adam/0000-0002-5593-9387; Angeletti,
Davide/0000-0002-5256-1972
FU National Institute of Allergy and Infectious Diseases Division of
Intramural Research; Food and Drug Administration Centers for Drug
Evaluation and Research
FX This work was generously supported by the National Institute of Allergy
and Infectious Diseases Division of Intramural Research and Food and
Drug Administration Centers for Drug Evaluation and Research.
NR 49
TC 2
Z9 2
U1 1
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2150-7511
J9 MBIO
JI mBio
PD JUL-AUG
PY 2015
VL 6
IS 4
AR e01156-15
DI 10.1128/mBio.01156-15
PG 11
WC Microbiology
SC Microbiology
GA CQ8EN
UT WOS:000360839400046
PM 26242629
ER
PT J
AU Qian, Z
Macvanin, M
Dimitriadis, EK
He, XM
Zhurkin, V
Adhya, S
AF Qian, Zhong
Macvanin, Mirjana
Dimitriadis, Emilios K.
He, Ximiao
Zhurkin, Victor
Adhya, Sankar
TI A New Noncoding RNA Arranges Bacterial Chromosome Organization
SO MBIO
LA English
DT Article
ID ESCHERICHIA-COLI CHROMOSOME; THERMOANAEROBACTER-TENGCONGENSIS;
REPETITIVE DNA; GAL PROMOTERS; PROTEIN HU; IN-VIVO; BINDING;
TRANSCRIPTION; SYSTEM; BIME
AB Repeated extragenic palindromes (REPs) in the enterobacterial genomes are usually composed of individual palindromic units separated by linker sequences. A total of 355 annotated REPs are distributed along the Escherichia coli genome. RNA sequence (RNAseq) analysis showed that almost 80% of the REPs in E. coli are transcribed. The DNA sequence of REP325 showed that it is a cluster of six repeats, each with two palindromic units capable of forming cruciform structures in supercoiled DNA. Here, we report that components of the REP325 element and at least one of its RNA products play a role in bacterial nucleoid DNA condensation. These RNA not only are present in the purified nucleoid but bind to the bacterial nucleoid-associated HU protein as revealed by RNA IP followed by microarray analysis (RIP-Chip) assays. Deletion of REP325 resulted in a dramatic increase of the nucleoid size as observed using transmission electron microscopy (TEM), and expression of one of the REP325 RNAs, nucleoid-associated noncoding RNA 4 (naRNA4), from a plasmid restored the wild-type condensed structure. Independently, chromosome conformation capture (3C) analysis demonstrated physical connections among various REP elements around the chromosome. These connections are dependent in some way upon the presence of HU and the REP325 element; deletion of HU genes and/or the REP325 element removed the connections. Finally, naRNA4 together with HU condensed DNA in vitro by connecting REP325 or other DNA sequences that contain cruciform structures in a pairwise manner as observed by atomic force microscopy (AFM). On the basis of our results, we propose molecular models to explain connections of remote cruciform structures mediated by HU and naRNA4.
IMPORTANCE Nucleoid organization in bacteria is being studied extensively, and several models have been proposed. However, the molecular nature of the structural organization is not well understood. Here we characterized the role of a novel nucleoid-associated noncoding RNA, naRNA4, in nucleoid structures both in vivo and in vitro. We propose models to explain how naRNA4 together with nucleoid-associated protein HU connects remote DNA elements for nucleoid condensation. We present the first evidence of a noncoding RNA together with a nucleoid-associated protein directly condensing nucleoid DNA.
C1 [Qian, Zhong; Macvanin, Mirjana; Adhya, Sankar] NCI, Mol Biol Lab, Bethesda, MD 20892 USA.
[Dimitriadis, Emilios K.] Natl Inst Biomed Imaging & Bioengn, Biomed Engn & Phys Sci, Bethesda, MD USA.
[He, Ximiao] NCI, Lab Metab, Bethesda, MD 20892 USA.
[Zhurkin, Victor] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Adhya, S (reprint author), NCI, Mol Biol Lab, Bldg 37, Bethesda, MD 20892 USA.
EM sadhya@helix.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research.
NR 38
TC 2
Z9 2
U1 2
U2 10
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2150-7511
J9 MBIO
JI mBio
PD JUL-AUG
PY 2015
VL 6
IS 4
AR e00998-15
DI 10.1128/mBio.00998-15
PG 8
WC Microbiology
SC Microbiology
GA CQ8EN
UT WOS:000360839400059
ER
PT J
AU Schwartzman, LM
Cathcart, AL
Pujanauski, LM
Qi, L
Kash, JC
Taubenberger, JK
AF Schwartzman, Louis M.
Cathcart, Andrea L.
Pujanauski, Lindsey M.
Qi, Li
Kash, John C.
Taubenberger, Jeffery K.
TI An Intranasal Virus-Like Particle Vaccine Broadly Protects Mice from
Multiple Subtypes of Influenza A Virus
SO MBIO
LA English
DT Article
ID IMMUNE-RESPONSES; AVIAN INFLUENZA; LETHAL 1918; HEMAGGLUTININ;
NEURAMINIDASE; ANTIBODIES; CHALLENGE; IMMUNIZATION; EVOLUTION; INFECTION
AB Influenza virus infections are a global public health problem, with a significant impact of morbidity and mortality from both annual epidemics and pandemics. The current strategy for preventing annual influenza is to develop a new vaccine each year against specific circulating virus strains. Because these vaccines are unlikely to protect against an antigenically divergent strain or a new pandemic virus with a novel hemagglutinin (HA) subtype, there is a critical need for vaccines that protect against all influenza A viruses, a so-called "universal" vaccine. Here we show that mice were broadly protected against challenge with a wide variety of lethal influenza A virus infections (94% aggregate survival following vaccination) with a virus-like particle (VLP) vaccine cocktail. The vaccine consisted of a mixture of VLPs individually displaying H1, H3, H5, or H7 HAs, and vaccinated mice showed significant protection following challenge with influenza viruses expressing 1918 H1, 1957 H2, and avian H5, H6, H7, H10, and H11 hemagglutinin subtypes. These experiments suggest a promising and practical strategy for developing a broadly protective "universal" influenza vaccine.
IMPORTANCE The rapid and unpredictable nature of influenza A virus evolution requires new vaccines to be produced annually to match circulating strains. Human infections with influenza viruses derived from animals can cause outbreaks that may be associated with high mortality, and such strains may also adapt to humans to cause a future pandemic. Thus, there is a large public health need to create broadly protective, or "universal," influenza vaccines that could prevent disease from a wide variety of human and animal influenza A viruses. In this study, a noninfectious virus-like particle (VLP) vaccine was shown to offer significant protection against a variety of influenza A viruses in mice, suggesting a practical strategy to develop a universal influenza vaccine.
C1 [Schwartzman, Louis M.; Cathcart, Andrea L.; Pujanauski, Lindsey M.; Qi, Li; Kash, John C.; 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
OI Pujanandez, Lindsey/0000-0002-2982-3700
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 45
TC 12
Z9 12
U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2150-7511
J9 MBIO
JI mBio
PD JUL-AUG
PY 2015
VL 6
IS 4
AR e01044-15
DI 10.1128/mBio.01044-15
PG 9
WC Microbiology
SC Microbiology
GA CQ8EN
UT WOS:000360839400036
PM 26199334
ER
PT J
AU Sivan, G
Ormanoglu, P
Buehler, EC
Martin, SE
Moss, B
AF Sivan, Gilad
Ormanoglu, Pinar
Buehler, Eugen C.
Martin, Scott E.
Moss, Bernard
TI Identification of Restriction Factors by Human Genome-Wide RNA
Interference Screening of Viral Host Range Mutants Exemplified by
Discovery of SAMD9 and WDR6 as Inhibitors of the Vaccinia Virus
K1L(-)C7L(-) Mutant
SO MBIO
LA English
DT Article
ID FAMILIAL TUMORAL CALCINOSIS; ANKYRIN REPEAT; K1L GENE; I INTERFERON;
RABBIT-CELLS; PROTEIN; EXPRESSION; POXVIRUSES; C7L; PHOSPHORYLATION
AB RNA interference (RNAi) screens intended to identify host factors that restrict virus replication may fail if the virus already counteracts host defense mechanisms. To overcome this limitation, we are investigating the use of viral host range mutants that exhibit impaired replication in nonpermissive cells. A vaccinia virus (VACV) mutant with a deletion of both the C7L and K1L genes, K1L(-)C7L(-), which abrogates replication in human cells at a step prior to late gene expression, was chosen for this strategy. We carried out a human genome-wide small interfering RNA (siRNA) screen in HeLa cells infected with a VACV K1L(-)C7L(-) mutant that expresses the green fluorescent protein regulated by a late promoter. This positive-selection screen had remarkably low background levels and resulted in the identification of a few cellular genes, notably SAMD9 and WDR6, from approximately 20,000 tested that dramatically enhanced green fluorescent protein expression. Replication of the mutant virus was enabled by multiple siRNAs to SAMD9 or WDR6. Moreover, SAMD9 and WDR6 clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 knockout HeLa cell lines were permissive for replication of the K1L(-)C7L(-) mutant, in agreement with the siRNA data. Expression of exogenous SAMD9 or interferon regulatory factor 1 restricted replication of the K1L(-)C7L(-) mutant in the SAMD9(-/-) cells. Independent interactions of SAMD9 with the K1 and C7 proteins were suggested by immunoprecipitation. Knockout of WDR6 did not reduce the levels of SAMD9 and interactions of WDR6 with SAMD9, C7, and K1 proteins were not detected, suggesting that these restriction factors act independently but possibly in the same innate defense pathway.
IMPORTANCE The coevolution of microbial pathogens with cells has led to an arms race in which the invader and host continuously struggle to gain the advantage. For this reason, traditional siRNA screens may fail to uncover important immune mechanisms if the pathogens have already developed effective responses. However, host-restricted viral mutants have lost one or more defense genes needed for their replication in nonpermissive cells. By screening human genome libraries of short RNAs that inhibit the expression of individual host genes in nonpermissive cells, we identified SAMD9 and WDR6 as major restriction factors that prevented replication of a vaccinia virus mutant and suggest that host range screening can be generally useful for the investigation of host-pathogen interactions.
C1 [Sivan, Gilad; Moss, Bernard] NIAID, Viral Dis Lab, Bethesda, MD 20892 USA.
[Ormanoglu, Pinar; Buehler, Eugen C.; Martin, Scott E.] Natl Ctr Adv Translat Sci, Div Preclin Innovat, NIH, Bethesda, MD USA.
RP Moss, B (reprint author), NIAID, Viral Dis Lab, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM bmoss@nih.gov
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX The research was supported by funds from the Division of Intramural
Research, National Institute of Allergy and Infectious Diseases,
National Institutes of Health.
NR 34
TC 7
Z9 7
U1 1
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2150-7511
J9 MBIO
JI mBio
PD JUL-AUG
PY 2015
VL 6
IS 4
AR e01122-15
DI 10.1128/mBio.01122-15
PG 9
WC Microbiology
SC Microbiology
GA CQ8EN
UT WOS:000360839400045
PM 26242627
ER
PT J
AU Pasqualini, L
Bu, H
Puhr, M
Narisu, N
Rainer, J
Schlick, B
Schafer, G
Angelova, M
Trajanoski, Z
Borno, ST
Schweiger, MR
Fuchsberger, C
Klocker, H
AF Pasqualini, Lorenza
Bu, Huajie
Puhr, Martin
Narisu, Narisu
Rainer, Johannes
Schlick, Bettina
Schaefer, Georg
Angelova, Mihaela
Trajanoski, Zlatko
Boerno, Stefan T.
Schweiger, Michal R.
Fuchsberger, Christian
Klocker, Helmut
TI miR-22 and miR-29a Are Members of the Androgen Receptor Cistrome
Modulating LAMC1 and Mcl-1 in Prostate Cancer
SO MOLECULAR ENDOCRINOLOGY
LA English
DT Article
ID TO-MESENCHYMAL TRANSITION; MICRORNA EXPRESSION; TMPRSS2-ERG FUSION; BONE
METASTASIS; CELL-MIGRATION; SURVIVAL; DIFFERENTIATION; TUMORIGENESIS;
INVASION; GROWTH
AB The normal prostate as well as early stages and advanced prostate cancer (PCa) require a functional androgen receptor (AR) for growth and survival. The recent discovery of microRNAs (miRNAs) as novel effector molecules of AR disclosed the existence of an intricate network between AR, miRNAs and downstream target genes. In this study DUCaP cells, characterized by high content of wild-type AR and robust AR transcriptional activity, were chosen as the main experimental model. By integrative analysis of chromatin immunoprecipitation-sequencing (ChIP-seq) and microarray expression profiling data, miRNAs putatively bound and significantly regulated by AR were identified. A direct AR regulation of miR-22, miR-29a, and miR-17-92 cluster along with their host genes was confirmed. Interestingly, endogenous levels of miR-22 and miR-29a were found to be reduced in PCa cells expressing AR. In primary tumor samples, miR-22 and miR-29a were less abundant in the cancerous tissue compared with the benign counterpart. This specific expression pattern was associated with a differential DNA methylation of the genomic AR binding sites. The identification of laminin gamma 1 (LAMC1) and myeloid cell leukemia 1 (MCL1) as direct targets of miR-22 and miR-29a, respectively, suggested a tumor-suppressive role of these miRNAs. Indeed, transfection of miRNA mimics in PCa cells induced apoptosis and diminished cell migration and viability. Collectively, these data provide additional information regarding the complex regulatory machinery that guides miRNAs activity in PCa, highlighting an important contribution of miRNAs in the AR signaling.
C1 [Pasqualini, Lorenza; Bu, Huajie; Puhr, Martin; Schlick, Bettina; Schaefer, Georg; Klocker, Helmut] Med Univ Innsbruck, Dept Urol, Div Expt Urol, A-6020 Innsbruck, Austria.
[Bu, Huajie] Univ Innsbruck, Res Inst Biomed Aging Res, A-6020 Innsbruck, Austria.
[Narisu, Narisu] NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA.
[Rainer, Johannes] Med Univ Innsbruck, Sect Mol Pathophysiol, Bioctr Innsbruck, A-6020 Innsbruck, Austria.
[Rainer, Johannes; Fuchsberger, Christian] EURAC Bolzano, Ctr Biomed, I-39100 Bolzano, Italy.
[Schlick, Bettina] Ctr Personalized Canc Med, Oncotyrol, A-6020 Innsbruck, Austria.
[Schaefer, Georg] Med Univ Innsbruck, Dept Pathol, A-6020 Innsbruck, Austria.
[Angelova, Mihaela; Trajanoski, Zlatko] Med Univ Innsbruck, Div Bioinformat, Bioctr Innsbruck, A-6020 Innsbruck, Austria.
[Boerno, Stefan T.; Schweiger, Michal R.] Max Planck Inst Mol Genet, D-14195 Berlin, Germany.
[Schweiger, Michal R.] Univ Cologne, Cologne Ctr Genom, D-50931 Cologne, Germany.
[Fuchsberger, Christian] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
RP Klocker, H (reprint author), Med Univ Innsbruck, Dept Urol, Anichstr 35, A-6020 Innsbruck, Austria.
EM helmut.klocker@i-med.ac.at
OI Fuchsberger, Christian/0000-0002-5918-8947
FU Molecular Cell Biology and Oncology (MCBO) doctoral college - Austrian
Research Fund (FWF) [W1101]; Intramural program of National Human Genome
Research Institute (NHGRI); NIH; Lichtenberg program
(VolkswagenStiftung)
FX This work was supported by the Molecular Cell Biology and Oncology
(MCBO) doctoral college funded by the Austrian Research Fund (FWF,
Project W1101). N.N. was supported by the Intramural program of National
Human Genome Research Institute (NHGRI), NIH; and M.R.S. by the
Lichtenberg program (VolkswagenStiftung).
NR 78
TC 9
Z9 9
U1 0
U2 5
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0888-8809
J9 MOL ENDOCRINOL
JI Mol. Endocrinol.
PD JUL
PY 2015
VL 29
IS 7
BP 1037
EP 1054
DI 10.1210/me.2014-1358
PG 18
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CR0DH
UT WOS:000360987900008
PM 26052614
ER
PT J
AU Lassman, AB
Pugh, SL
Gilbert, MR
Aldape, KD
Geinoz, S
Beumer, JH
Christner, SM
Komaki, R
DeAngelis, LM
Gaur, R
Youssef, E
Wagner, H
Won, M
Mehta, MP
AF Lassman, Andrew B.
Pugh, Stephanie L.
Gilbert, Mark R.
Aldape, Kenneth D.
Geinoz, Sandrine
Beumer, Jan H.
Christner, Susan M.
Komaki, Ritsuko
DeAngelis, Lisa M.
Gaur, Rakesh
Youssef, Emad
Wagner, Henry
Won, Minhee
Mehta, Minesh P.
TI Phase 2 trial of dasatinib in target-selected patients with recurrent
glioblastoma (RTOG 0627)
SO NEURO-ONCOLOGY
LA English
DT Article
DE chemotherapy; dasatinib; glioblastoma; phase II; tyrosine kinase
inhibitor
ID NEWLY-DIAGNOSED GLIOBLASTOMA; PROGRESSION-FREE SURVIVAL; CHRONIC
MYELOID-LEUKEMIA; GROWTH-FACTOR RECEPTOR; II CLINICAL-TRIALS; MALIGNANT
GLIOMA; LUNG-CANCER; BEVACIZUMAB; MULTIFORME; IMATINIB
AB Background. We conducted a phase II trial to evaluate the efficacy of dasatinib, a multitargeted tyrosine kinase inhibitor, for adults with recurrent glioblastoma (GBM).
Methods. Eligibility requirements were Karnofsky performance status >= 60%; no concurrent hepatic enzyme-inducing anticonvulsants; prior treatment with surgery, radiotherapy, and temozolomide exclusively; and activation or overexpression of = 2 putative dasatinib targets in GBM (ie, SRC, c-KIT, EPHA2, and PDGFR). Using a 2-stage design, 77 eligible participants (27 in stage 1, if favorable, and then 50 in stage 2) were needed to detect an absolute improvement in the proportion of patients either alive and progression- free patients at 6 months (6mPFS) or responding (any duration) from a historical 11% to 25%.
Results. A high rate of ineligibility (27%) to stage 1 precluded a powered assessment of efficacy, but there was also infrequent treatment-related toxicity at 100 mg twice daily. Therefore, the study was redesigned to allow intrapatient escalation by 50 mg daily every cycle as tolerated (stage 1B) before determining whether to proceed to stage 2. Escalation was tolerable in 10 of 17 (59%) participants evaluable for that endpoint; however, among all eligible patients (stages 1 and 1B, n = 50), there were no radiographic responses, median overall survival was 7.9 months, median PFS was 1.7 months, and the 6mPFS rate was 6%. The clinical benefit was insufficient to correlate tested biomarkers with efficacy. The trial was closed without proceeding to stage 2.
Conclusions. Intraparticipant dose escalation was feasible, but dasatinib was ineffective in recurrent GBM. Clinical trials. gov identified. NCT00423735 (available at http://clinicaltrials.gov/ct2/show/NCT00423735).
C1 [Lassman, Andrew B.] Columbia Univ, Med Ctr, Dept Neurol, New York, NY USA.
[Lassman, Andrew B.] Columbia Univ, Med Ctr, Herbert Irving Comprehens Canc Ctr, New York, NY USA.
[Lassman, Andrew B.; DeAngelis, Lisa M.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Pugh, Stephanie L.; Geinoz, Sandrine; Won, Minhee] NRG Oncol Stat & Data Management Ctr, Philadelphia, PA USA.
[Gilbert, Mark R.; Aldape, Kenneth D.; Komaki, Ritsuko] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Gilbert, Mark R.] NCI, Neurooncol Branch, NINDS, NIH, Bethesda, MD 20892 USA.
[Aldape, Kenneth D.] Univ Toronto, Toronto, ON, Canada.
[Aldape, Kenneth D.] Princess Margaret Canc Ctr, Toronto, ON, Canada.
[Beumer, Jan H.; Christner, Susan M.] Univ Pittsburgh, Inst Canc, Canc Therapeut Program, Pittsburgh, PA USA.
[Beumer, Jan H.] Univ Pittsburgh, Sch Pharm Pittsburgh, Dept Pharmaceut Sci, Pittsburgh, PA 15260 USA.
[Gaur, Rakesh] NCI Community Oncol Res Program, Kansas City, KS USA.
[Youssef, Emad] Arizona Oncol Serv Fdn, Tucson, AZ USA.
[Wagner, Henry] Penn State Univ, Hershey, PA USA.
[Wagner, Henry] Penn State Univ Hosp, Milton S Hershey Med Ctr, Hershey, PA 17033 USA.
[Mehta, Minesh P.] Univ Maryland Med Syst, Baltimore, MD USA.
RP Lassman, AB (reprint author), Columbia Univ, Med Ctr, Dept Neurol, 710 West 168th St, New York, NY 10027 USA.
EM ABL7@cumc.columbia.edu
RI Gilbert, Mark/J-7494-2016;
OI Gilbert, Mark/0000-0003-2556-9722; mehta, minesh/0000-0002-4812-5713;
Beumer, Jan/0000-0002-8978-9401
FU Radiation Therapy Oncology Group (RTOG) [U10 CA21661]; CCOP from
National Cancer Institute (NCI) [U10 CA37422]; Bristol-Myers Squibb
[P30-CA47904]
FX This projected was supported by Radiation Therapy Oncology Group (RTOG)
grant U10 CA21661 and CCOP grant U10 CA37422 from the National Cancer
Institute (NCI) and Bristol-Myers Squibb. Pharmacokinetic analyses were
conducted using the University of Pittsburgh Cancer Institute Cancer
Pharmacokinetics and Pharmacodynamics Facility (CPPF) and were supported
in part by Bristol-Myers Squibb and award P30-CA47904. This manuscript's
contents are solely the responsibility
NR 41
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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 1522-8517
EI 1523-5866
J9 NEURO-ONCOLOGY
JI Neuro-Oncology
PD JUL
PY 2015
VL 17
IS 7
BP 992
EP 998
DI 10.1093/neuonc/nov011
PG 7
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA CR0BM
UT WOS:000360983200012
PM 25758746
ER
PT J
AU Kumar, A
Colon-Ramos, DA
Shroff, H
AF Kumar, Abhishek
Colon-Ramos, Daniel A.
Shroff, Hari
TI Watching a roundworm develop with a sheet of light
SO PHYSICS TODAY
LA English
DT Editorial Material
C1 [Kumar, Abhishek] Yale Univ, New Haven, CT 06520 USA.
[Kumar, Abhishek] NIBIB, NIH, Bethesda, MD USA.
[Colon-Ramos, Daniel A.] Yale Univ, Cell Biol & Cellular Neurosci, New Haven, CT USA.
[Shroff, Hari] NIBIB, Sect High Resolut Opt Imaging, Bethesda, MD USA.
[Shroff, Hari] NIBIB, Bethesda, MD USA.
RP Kumar, A (reprint author), Yale Univ, New Haven, CT 06520 USA.
RI Shroff, Hari/E-7247-2016
OI Shroff, Hari/0000-0003-3613-8215
NR 0
TC 2
Z9 2
U1 0
U2 1
PU AMER INST PHYSICS
PI MELVILLE
PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA
SN 0031-9228
EI 1945-0699
J9 PHYS TODAY
JI Phys. Today
PD JUL
PY 2015
VL 68
IS 7
BP 58
EP 59
PG 2
WC Physics, Multidisciplinary
SC Physics
GA CQ9HO
UT WOS:000360924700021
ER
PT J
AU Higuchi, M
Chen, RD
Abbott, RD
Bell, C
Launer, L
Ross, GW
Petrovitch, H
Masaki, K
AF Higuchi, Masaya
Chen, Randi
Abbott, Robert D.
Bell, Christina
Launer, Lenore
Ross, G. Webster
Petrovitch, Helen
Masaki, Kamal
TI Mid-Life Proteinuria and Late-Life Cognitive Function and Dementia in
Elderly Men The Honolulu-Asia Aging Study
SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS
LA English
DT Article
DE dementia; cognitive decline; proteinuria; Japanese-American men;
longitudinal cohort study
ID CHRONIC KIDNEY-DISEASE; JAPANESE-AMERICAN MEN; ALZHEIMERS-DISEASE;
OLDER-ADULTS; VASCULAR DEMENTIA; BLOOD-PRESSURE; INFORMANT
QUESTIONNAIRE; HEART-PROGRAM; RISK-FACTOR; DECLINE
AB Background:Impaired renal function has been linked to cognitive impairment. We assessed mid-life proteinuria and late-life cognitive function in elderly Asian men.Methods:The Honolulu Heart Program is a prospective study that began in 1965 with 8006 Japanese-American men aged 45 to 68 years. Mid-life proteinuria was detected by urine dipstick in 1971 to 1974. The Honolulu-Asia Aging Study began 20 years later, with cognitive assessment by the Cognitive Abilities Screening Instrument (CASI) in 3734 men. Standard criteria were used to classify 8-year incident dementia and subtypes.Results:The age-adjusted incidence of dementia increased significantly from 13.8, to 22.8, to 39.7 per 1000 person years follow-up, among those with no, trace, and positive mid-life proteinuria (P=0.004). Using linear regression adjusting for age, education, APOE epsilon 4, stroke, hypertension, systolic blood pressure, diabetes, fasting blood glucose, physical activity, and baseline CASI, those with positive proteinuria had significantly higher annual change in CASI over 8 years follow-up (-1.24, P=0.02) (reference=no proteinuria). Multivariate Cox regression found that positive proteinuria had a significant association with incident all-cause dementia (RR=2.66; 95%CI, 1.09-6.53; P=0.03), but no significant associations with incident Alzheimer disease or vascular dementia.Conclusion:Mid-life proteinuria was an independent predictor for late-life incident all-cause dementia and cognitive decline over 8 years.
C1 [Higuchi, Masaya; Abbott, Robert D.; Bell, Christina; Ross, G. Webster; Petrovitch, Helen; Masaki, Kamal] Univ Hawaii, John A Burns Sch Med, Dept Geriatr Med, John A Hartford Fdn,Ctr Excellence Geriatr, Honolulu, HI 96822 USA.
[Chen, Randi; Masaki, Kamal] Kuakini Med Ctr, Honolulu, HI USA.
[Ross, G. Webster; Petrovitch, Helen] Vet Affairs Pacific Isl Hlth Care Syst, Honolulu, HI USA.
[Higuchi, Masaya] So Illinois Univ, Sch Med, Dept Family & Community Med, Springfield, IL 62702 USA.
[Abbott, Robert D.] Shiga Univ Med Sci, Ctr Epidemiol Res Asia, Otsu, Shiga 52021, Japan.
[Launer, Lenore] NIA, Bethesda, MD 20892 USA.
RP Higuchi, M (reprint author), So Illinois Univ, Sch Med, Dept Family & Community Med, 520N 4th St, Springfield, IL 62702 USA.
EM higuchimasaya@gmail.com
FU John A. Hartford Foundation Center of Excellence in Geriatrics,
Department of Geriatric Medicine, John A. Burns School of Medicine,
University of Hawaii; Kuakini Medical Center; National Institutes of
Health (National Heart, Lung, and Blood Institute) [N01-HC-05102];
National Institutes of Health (National Institute on Aging)
[U01-AG019349, R01AG027060, R01AG038707]; National Institutes of Health
(Hawaii Community Foundation) [2004-0463]; National Institutes of Health
(Office for Research and Development, Department of Veterans Affairs);
National Institutes of Health (Kuakini Medical Center); National
Institute on Aging; National Institute of Neurological Disorders and
Stroke; National Institutes of Health
FX Supported by the John A. Hartford Foundation Center of Excellence in
Geriatrics, Department of Geriatric Medicine, John A. Burns School of
Medicine, University of Hawaii; Kuakini Medical Center; the National
Institutes of Health (Contract N01-HC-05102 from the National Heart,
Lung, and Blood Institute, and Contract N01-AG-4-2149 and Grants
U01-AG019349, R01AG027060, and R01AG038707 from the National Institute
on Aging, Kuakini Medical Center, Hawaii Community Foundation grant
2004-0463, and the Office for Research and Development, Department of
Veterans Affairs).; H.P. works for the Pacific Health Research &
Education Institute and receives salary from grants from the National
Institute on Aging and the National Institute of Neurological Disorders
and Stroke. K.M. received grant funding from National Institutes of
Health grants. The remaining authors declare no conflicts of interest.
NR 41
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PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0893-0341
J9 ALZ DIS ASSOC DIS
JI Alzheimer Dis. Assoc. Dis.
PD JUL-SEP
PY 2015
VL 29
IS 3
BP 200
EP 205
DI 10.1097/WAD.0000000000000082
PG 6
WC Clinical Neurology; Pathology
SC Neurosciences & Neurology; Pathology
GA CQ5PX
UT WOS:000360658900004
PM 25626635
ER
PT J
AU Chari, ST
Kelly, K
Hollingsworth, MA
Thayer, SP
Ahlquist, DA
Andersen, DK
Batra, SK
Brentnall, TA
Canto, M
Cleeter, DF
Firpo, MA
Gambhir, SS
Go, VLW
Hines, OJ
Kenner, BJ
Klimstra, DS
Lerch, MM
Levy, MJ
Maitra, A
Mulvihill, SJ
Petersen, GM
Rhim, AD
Simeone, DM
Srivastava, S
Tanaka, M
Vinik, AI
Wong, D
AF Chari, Suresh T.
Kelly, Kimberly
Hollingsworth, Michael A.
Thayer, Sarah P.
Ahlquist, David A.
Andersen, Dana K.
Batra, Surinder K.
Brentnall, Teresa A.
Canto, Marcia
Cleeter, Deborah F.
Firpo, Matthew A.
Gambhir, Sanjiv Sam
Go, Vay Liang W.
Hines, O. Joe
Kenner, Barbara J.
Klimstra, David S.
Lerch, Markus M.
Levy, Michael J.
Maitra, Anirban
Mulvihill, Sean J.
Petersen, Gloria M.
Rhim, Andrew D.
Simeone, Diane M.
Srivastava, Sudhir
Tanaka, Masao
Vinik, Aaron I.
Wong, David
TI Early Detection of Sporadic Pancreatic Cancer Summative Review
SO PANCREAS
LA English
DT Review
DE biomarker; diabetes; screening; familial; imaging; pancreatic ductal
adenocarcinoma
AB Pancreatic cancer (PC) is estimated to become the second leading cause of cancer death in the United States by 2020. Early detection is the key to improving survival in PC. Addressing this urgent need, the Kenner Family Research Fund conducted the inaugural Early Detection of Sporadic Pancreatic Cancer Summit Conference in 2014 in conjunction with the 45th Anniversary Meeting of the American Pancreatic Association and Japan Pancreas Society. This seminal convening of international representatives from science, practice, and clinical research was designed to facilitate challenging interdisciplinary conversations to generate innovative ideas leading to the creation of a defined collaborative strategic pathway for the future of the field. An in-depth summary of current efforts in the field, analysis of gaps in specific areas of expertise, and challenges that exist in early detection is presented within distinct areas of inquiry: Case for Early Detection: Definitions, Detection, Survival, and Challenges; Biomarkers for Early Detection; Imaging; and Collaborative Studies. In addition, an overview of efforts in familial PC is presented in an addendum to this article. It is clear from the summit deliberations that only strategically designed collaboration among investigators, institutions, and funders will lead to significant progress in early detection of sporadic PC.
C1 [Chari, Suresh T.; Ahlquist, David A.] Mayo Clin, Dept Med, Rochester, MN USA.
[Kelly, Kimberly] Univ Virginia, Dept Biomed Engn, Charlottesville, VA USA.
[Hollingsworth, Michael A.; Batra, Surinder K.] Univ Nebraska, Fred & Pamela Buffett Canc Ctr, Dept Biochem & Mol Biol, Omaha, NE 68182 USA.
[Hollingsworth, Michael A.] Univ Nebraska, Fred & Pamela Buffett Canc Ctr, Dept Pathol & Microbiol, Omaha, NE 68182 USA.
[Thayer, Sarah P.; Levy, Michael J.] Univ Nebraska, Fred & Pamela Buffett Canc Ctr, Dept Surg, Omaha, NE 68182 USA.
[Andersen, Dana K.] NIDDK, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA.
[Brentnall, Teresa A.] Univ Washington, Div Gastroenterol, Seattle, WA 98195 USA.
[Canto, Marcia] Johns Hopkins Univ, Sch Med, Div Gastroenterol, Baltimore, MD USA.
[Cleeter, Deborah F.] Sawgrass Leadership Inst, Ponte Vedra Beach, FL USA.
[Firpo, Matthew A.; Mulvihill, Sean J.] Univ Utah, Dept Surg, Salt Lake City, UT USA.
[Gambhir, Sanjiv Sam] Stanford Univ, Sch Med, Dept Radiol, Stanford, CA 94305 USA.
[Go, Vay Liang W.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
[Hines, O. Joe] Univ Calif Los Angeles, Gen Surg, Los Angeles, CA USA.
[Kenner, Barbara J.] Kenner Family Res Fund, New York, NY 10075 USA.
[Klimstra, David S.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA.
[Lerch, Markus M.] Ernst Moritz Arndt Univ Greifswald, Dept Internal Med, Greifswald, Germany.
[Maitra, Anirban] Univ Texas MD Anderson Canc Ctr, Div Pathol & Lab Med, Houston, TX 77030 USA.
[Petersen, Gloria M.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
[Rhim, Andrew D.] Univ Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA.
[Rhim, Andrew D.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
[Simeone, Diane M.] Univ Michigan, Sch Med, Dept Surg, Ann Arbor, MI USA.
[Srivastava, Sudhir] NCI, Canc Biomarkers Res Grp, Canc Prevent Div, Rockville, MD USA.
[Tanaka, Masao] Kyushu Univ, Dept Surg, Fukuoka 812, Japan.
[Tanaka, Masao] Kyushu Univ, Dept Oncol, Fukuoka 812, Japan.
[Vinik, Aaron I.] Eastern Virginia Med Sch, Dept Med, Norfolk, VA 23501 USA.
[Wong, David] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, CLA Sch Dent, Div Oral Biol & Med, Los Angeles, CA 90024 USA.
RP Kenner, BJ (reprint author), Kenner Family Res Fund, New York, NY 10075 USA.
EM chari.suresh@mayo.edu; drbkenner@kennerfamilyresearchfund.org
RI Lerch, Markus M./E-2206-2016
OI Lerch, Markus M./0000-0002-9643-8263
FU NCI NIH HHS [R01 CA168712, R01 CA177857]
NR 0
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U1 3
U2 13
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0885-3177
EI 1536-4828
J9 PANCREAS
JI Pancreas
PD JUL
PY 2015
VL 44
IS 5
BP 693
EP 712
DI 10.1097/MPA.0000000000000368
PG 20
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CQ5FS
UT WOS:000360629300003
PM 25931254
ER
PT J
AU Berman, FD
Bourne, PE
AF Berman, Francine D.
Bourne, Philip E.
TI Let's Make Gender Diversity in Data Science a Priority Right from the
Start
SO PLOS BIOLOGY
LA English
DT Article
AB The emergent field of data science is a critical driver for innovation in all sectors, a focus of tremendous workforce development, and an area of increasing importance within science, technology, engineering, and math (STEM). In all of its aspects, data science has the potential to narrow the gender gap and set a new bar for inclusion. To evolve data science in a way that promotes gender diversity, we must address two challenges: (1) how to increase the number of women acquiring skills and working in data science and (2) how to evolve organizations and professional cultures to better retain and advance women in data science. Everyone can contribute.
C1 [Berman, Francine D.] Rensselaer Polytech Inst, Dept Comp Sci, Troy, NY 12180 USA.
[Bourne, Philip E.] NIH, Off Director, Bethesda, MD 20892 USA.
RP Berman, FD (reprint author), Rensselaer Polytech Inst, Dept Comp Sci, Troy, NY 12180 USA.
EM BERMAF@rpi.edu
NR 12
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U1 3
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1545-7885
J9 PLOS BIOL
JI PLoS. Biol.
PD JUL
PY 2015
VL 13
IS 7
AR e1002206
DI 10.1371/journal.pbio.1002206
PG 5
WC Biochemistry & Molecular Biology; Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics
GA CQ5BA
UT WOS:000360617100018
PM 26213996
ER
PT J
AU Fuertinger, S
Horwitz, B
Simonyan, K
AF Fuertinger, Stefan
Horwitz, Barry
Simonyan, Kristina
TI The Functional Connectome of Speech Control
SO PLOS BIOLOGY
LA English
DT Article
ID PRIMARY MOTOR CORTEX; GLOBAL SIGNAL REGRESSION; EVENT-RELATED FMRI;
WORKING-MEMORY; HUMAN BRAIN; EFFECTIVE CONNECTIVITY; SMALL-WORLD;
CORTICAL INTERACTIONS; STRUCTURAL NETWORKS; LANGUAGE PRODUCTION
AB In the past few years, several studies have been directed to understanding the complexity of functional interactions between different brain regions during various human behaviors. Among these, neuroimaging research installed the notion that speech and language require an orchestration of brain regions for comprehension, planning, and integration of a heard sound with a spoken word. However, these studies have been largely limited to mapping the neural correlates of separate speech elements and examining distinct cortical or subcortical circuits involved in different aspects of speech control. As a result, the complexity of the brain network machinery controlling speech and language remained largely unknown. Using graph theoretical analysis of functional MRI (fMRI) data in healthy subjects, we quantified the large-scale speech network topology by constructing functional brain networks of increasing hierarchy from the resting state to motor output of meaningless syllables to complex production of real-life speech as well as compared to non-speech-related sequential finger tapping and pure tone discrimination networks. We identified a segregated network of highly connected local neural communities (hubs) in the primary sensorimotor and parietal regions, which formed a commonly shared core hub network across the examined conditions, with the left area 4p playing an important role in speech network organization. These sensorimotor core hubs exhibited features of flexible hubs based on their participation in several functional domains across different networks and ability to adaptively switch long-range functional connectivity depending on task content, resulting in a distinct community structure of each examined network. Specifically, compared to other tasks, speech production was characterized by the formation of six distinct neural communities with specialized recruitment of the prefrontal cortex, insula, putamen, and thalamus, which collectively forged the formation of the functional speech connectome. In addition, the observed capacity of the primary sensorimotor cortex to exhibit operational heterogeneity challenged the established concept of unimodality of this region.
C1 [Fuertinger, Stefan; Simonyan, Kristina] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA.
[Horwitz, Barry] NIDCD, Brain Imaging & Modeling Sect, NIH, Bethesda, MD USA.
[Simonyan, Kristina] Icahn Sch Med Mt Sinai, Dept Otolaryngol, New York, NY 10029 USA.
RP Fuertinger, S (reprint author), Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA.
EM kristina.simonyan@mssm.edu
OI Simonyan, Kristina/0000-0001-7444-0437; Fuertinger,
Stefan/0000-0002-8118-036X
FU National Institute on Deafness and Other Communication Disorders
[R01DC011805, R01DC012545]; Intramural Program of the National Institute
on Deafness and Other Communication Disorders
FX Supported by the grants from the National Institute on Deafness and
Other Communication Disorders (R01DC011805 and R01DC012545) to KS and
the Intramural Program of the National Institute on Deafness and Other
Communication Disorders to BH. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 106
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U1 6
U2 18
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1545-7885
J9 PLOS BIOL
JI PLoS. Biol.
PD JUL
PY 2015
VL 13
IS 7
AR e1002209
DI 10.1371/journal.pbio.1002209
PG 31
WC Biochemistry & Molecular Biology; Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics
GA CQ5BA
UT WOS:000360617100021
PM 26204475
ER
PT J
AU Read, AF
Baigent, SJ
Powers, C
Kgosana, LB
Blackwell, L
Smith, LP
Kennedy, DA
Walkden-Brown, SW
Nair, VK
AF Read, Andrew F.
Baigent, Susan J.
Powers, Claire
Kgosana, Lydia B.
Blackwell, Luke
Smith, Lorraine P.
Kennedy, David A.
Walkden-Brown, Stephen W.
Nair, Venugopal K.
TI Imperfect Vaccination Can Enhance the Transmission of Highly Virulent
Pathogens
SO PLOS BIOLOGY
LA English
DT Article
ID MAREKS-DISEASE VIRUS; MICROBIAL EVOLUTION; INFECTIOUS-DISEASES;
ANTITOXIN VACCINES; FEATHER DANDER; MDV INFECTION; CHICKENS; POULTRY;
MODEL; HERPESVIRUS
AB Could some vaccines drive the evolution of more virulent pathogens? Conventional wisdom is that natural selection will remove highly lethal pathogens if host death greatly reduces transmission. Vaccines that keep hosts alive but still allow transmission could thus allow very virulent strains to circulate in a population. Here we show experimentally that immunization of chickens against Marek's disease virus enhances the fitness of more virulent strains, making it possible for hyperpathogenic strains to transmit. Immunity elicited by direct vaccination or by maternal vaccination prolongs host survival but does not prevent infection, viral replication or transmission, thus extending the infectious periods of strains otherwise too lethal to persist. Our data show that anti-disease vaccines that do not prevent transmission can create conditions that promote the emergence of pathogen strains that cause more severe disease in unvaccinated hosts.
C1 [Read, Andrew F.; Kennedy, David A.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
[Read, Andrew F.; Kennedy, David A.] Penn State Univ, Dept Entomol, University Pk, PA 16802 USA.
[Read, Andrew F.; Kennedy, David A.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Baigent, Susan J.; Powers, Claire; Kgosana, Lydia B.; Blackwell, Luke; Smith, Lorraine P.; Nair, Venugopal K.] Pirbright Inst, Avian Oncogen Virus Grp, Newbury, Berks, England.
[Walkden-Brown, Stephen W.] Univ New England, Sch Environm & Rural Sci, Armidale, NSW, Australia.
RP Read, AF (reprint author), Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
EM a.read@psu.edu
RI Nair, Venugopal/D-4447-2016; Institute, Pirbright/K-4476-2014
OI Nair, Venugopal/0000-0002-8255-516X;
FU Institute of General Medical Sciences, National Institutes of Health
[R01GM105244]; UK Biotechnology and Biological Sciences Research Council
as part of NSF-NIH-USDA Ecology; Evolution of Infectious Diseases
program
FX This work was funded by the Institute of General Medical Sciences,
National Institutes of Health (R01GM105244) and by UK Biotechnology and
Biological Sciences Research Council as part of the joint NSF-NIH-USDA
Ecology and Evolution of Infectious Diseases program. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 61
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PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1545-7885
J9 PLOS BIOL
JI PLoS. Biol.
PD JUL
PY 2015
VL 13
IS 7
AR e1002198
DI 10.1371/journal.pbio.1002198
PG 18
WC Biochemistry & Molecular Biology; Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics
GA CQ5BA
UT WOS:000360617100012
PM 26214839
ER
PT J
AU Nussinov, R
Bonhoeffer, S
Papin, JA
Sporns, O
AF Nussinov, Ruth
Bonhoeffer, Sebastian
Papin, Jason A.
Sporns, Olaf
TI From "What Is?" to "What Isn't?" Computational Biology
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Editorial Material
C1 [Nussinov, Ruth] NCI, Canc & Inflammat Program, Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel.
[Bonhoeffer, Sebastian] ETH, Inst Integrat Biol, Theoret Biol Grp, Zurich, Switzerland.
[Papin, Jason A.] Univ Virginia, Dept Biomed Engn, Charlottesville, VA USA.
[Sporns, Olaf] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN USA.
RP Nussinov, R (reprint author), NCI, Canc & Inflammat Program, Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA.
EM nussinor@helix.nih.gov
RI Sporns, Olaf/A-1667-2010; Bonhoeffer, Sebastian/A-2735-2008
OI Sporns, Olaf/0000-0001-7265-4036; Bonhoeffer,
Sebastian/0000-0001-8052-3925
NR 0
TC 1
Z9 1
U1 0
U2 9
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-734X
EI 1553-7358
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD JUL
PY 2015
VL 11
IS 7
AR e1004318
DI 10.1371/journal.pcbi.1004318
PG 3
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA CQ5CE
UT WOS:000360620100018
PM 26134043
ER
PT J
AU Petukh, M
Li, MH
Alexov, E
AF Petukh, Marharyta
Li, Minghui
Alexov, Emil
TI Predicting Binding Free Energy Change Caused by Point Mutations with
Knowledge-Modified MM/PBSA Method
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Article
ID PROTEIN-PROTEIN INTERACTIONS; MOLECULAR-DYNAMICS; LIGAND BINDING;
AFFINITY; COMPLEXES; ORIGINS; IONIZATION; INTERFACES; STABILITY; SURFACE
AB A new methodology termed Single Amino Acid Mutation based change in Binding free Energy (SAAMBE) was developed to predict the changes of the binding free energy caused by mutations. The method utilizes 3D structures of the corresponding protein-protein complexes and takes advantage of both approaches: sequence- and structure-based methods. The method has two components: a MM/PBSA-based component, and an additional set of statistical terms delivered from statistical investigation of physico-chemical properties of protein complexes. While the approach is rigid body approach and does not explicitly consider plausible conformational changes caused by the binding, the effect of conformational changes, including changes away from binding interface, on electrostatics are mimicked with amino acid specific dielectric constants. This provides significant improvement of SAAMBE predictions as indicated by better match against experimentally determined binding free energy changes over 1300 mutations in 43 proteins. The final benchmarking resulted in a very good agreement with experimental data (correlation coefficient 0.624) while the algorithm being fast enough to allow for large-scale calculations (the average time is less than a minute per mutation).
C1 [Petukh, Marharyta; Alexov, Emil] Clemson Univ, Dept Phys, Computat Biophys & Bioinformat, Clemson, SC 29634 USA.
[Li, Minghui] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
RP Petukh, M (reprint author), Clemson Univ, Dept Phys, Computat Biophys & Bioinformat, Clemson, SC 29634 USA.
EM ealexov@clemson.edu
RI Li, Minghui/E-4339-2016
FU National Institutes of Health [R01GM093937]; Intramural Research Program
of the National Library of Medicine at the U.S. National Institutes of
Health
FX This work was funded by National Institutes of Health, R01GM093937 - MP
and EA, Intramural Research Program of the National Library of Medicine
at the U.S. National Institutes of Health ML (http://www.nih.gov/). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 52
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U1 3
U2 15
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-734X
EI 1553-7358
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD JUL
PY 2015
VL 11
IS 7
AR e1004276
DI 10.1371/journal.pcbi.1004276
PG 23
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA CQ5CE
UT WOS:000360620100011
PM 26146996
ER
PT J
AU Wesolowski, A
O'Meara, WP
Eagle, N
Tatem, AJ
Buckee, CO
AF Wesolowski, Amy
O'Meara, Wendy Prudhomme
Eagle, Nathan
Tatem, Andrew J.
Buckee, Caroline O.
TI Evaluating Spatial Interaction Models for Regional Mobility in
Sub-Saharan Africa
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Article
ID INFECTIOUS-DISEASES; GRAVITY MODEL; MOVEMENT; POPULATION; PATTERNS;
MALARIA; TRANSMISSION; MULTISCALE; EPIDEMICS; INFLUENZA
AB Simple spatial interaction models of human mobility based on physical laws have been used extensively in the social, biological, and physical sciences, and in the study of the human dynamics underlying the spread of disease. Recent analyses of commuting patterns and travel behavior in high-income countries have led to the suggestion that these models are highly generalizable, and as a result, gravity and radiation models have become standard tools for describing population mobility dynamics for infectious disease epidemiology. Communities in Sub-Saharan Africa may not conform to these models, however; physical accessibility, availability of transport, and cost of travel between locations may be variable and severely constrained compared to high-income settings, informal labor movements rather than regular commuting patterns are often the norm, and the rise of mega-cities across the continent has important implications for travel between rural and urban areas. Here, we first review how infectious disease frameworks incorporate human mobility on different spatial scales and use anonymous mobile phone data from nearly 15 million individuals to analyze the spatiotemporal dynamics of the Kenyan population. We find that gravity and radiation models fail in systematic ways to capture human mobility measured by mobile phones; both severely overestimate the spatial spread of travel and perform poorly in rural areas, but each exhibits different characteristic patterns of failure with respect to routes and volumes of travel. Thus, infectious disease frameworks that rely on spatial interaction models are likely to misrepresent population dynamics important for the spread of disease in many African populations.
C1 [Wesolowski, Amy; Eagle, Nathan; Buckee, Caroline O.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Wesolowski, Amy; Buckee, Caroline O.] Harvard Univ, Sch Publ Hlth, Ctr Communicable Dis Dynam, Boston, MA 02115 USA.
[O'Meara, Wendy Prudhomme] Duke Univ, Dept Med, Durham, NC USA.
[O'Meara, Wendy Prudhomme] Duke Global Hlth Inst, Durham, NC USA.
[Eagle, Nathan] Northeastern Univ, Coll Comp & Informat Sci, Boston, MA 02115 USA.
[Tatem, Andrew J.] Univ Southampton, Dept Geog & Environm, Southampton, Hants, England.
[Tatem, Andrew J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Wesolowski, A (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
EM cbuckee@hsph.harvard.edu
FU National Science Foundation Graduate Research Fellowship [0750271];
James S. McDonnell Foundation; Bill & Melinda Gates Foundation [49446,
OPP1032350]; NIH/NIAID grant [U19AI089674]; RAPIDD program of the
Science & Technology Directorate, Department of Homeland Security;
Fogarty International Center, National Institutes of Health; Models of
Infectious Disease Agent Study program [1U54GM088558]
FX AW was supported by the National Science Foundation Graduate Research
Fellowship program (#0750271) and a James S. McDonnell Foundation
fellowship. AJT acknowledges support from Bill & Melinda Gates
Foundation grants (#49446 and #OPP1032350), NIH/NIAID grant
(U19AI089674), and the RAPIDD program of the Science & Technology
Directorate, Department of Homeland Security, and the Fogarty
International Center, National Institutes of Health. COB was supported
by the Models of Infectious Disease Agent Study program (cooperative
agreement 1U54GM088558). The content is solely the responsibility of the
authors and does not necessarily represent the official views of the
National Institute of General Medical Sciences or the 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 44
TC 8
Z9 8
U1 2
U2 22
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-734X
EI 1553-7358
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD JUL
PY 2015
VL 11
IS 7
AR e1004267
DI 10.1371/journal.pcbi.1004267
PG 16
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA CQ5CE
UT WOS:000360620100009
PM 26158274
ER
PT J
AU Ding, J
Sidore, C
Butler, TJ
Wing, MK
Qian, Y
Meirelles, O
Busonero, F
Tsoi, LC
Maschio, A
Angius, A
Kang, HM
Nagaraja, R
Cucca, F
Abecasis, GR
Schlessinger, D
AF Ding, Jun
Sidore, Carlo
Butler, Thomas J.
Wing, Mary Kate
Qian, Yong
Meirelles, Osorio
Busonero, Fabio
Tsoi, Lam C.
Maschio, Andrea
Angius, Andrea
Kang, Hyun Min
Nagaraja, Ramaiah
Cucca, Francesco
Abecasis, Goncalo R.
Schlessinger, David
TI Assessing Mitochondrial DNA Variation and Copy Number in Lymphocytes of
similar to 2,000 Sardinians Using Tailored Sequencing Analysis Tools
SO PLOS GENETICS
LA English
DT Article
ID HUMAN TRANSCRIPTOME; WIDESPREAD RNA; HETEROPLASMY; MUTATIONS; DISEASE;
CANCER
AB DNA sequencing identifies common and rare genetic variants for association studies, but studies typically focus on variants in nuclear DNA and ignore the mitochondrial genome. In fact, analyzing variants in mitochondrial DNA (mtDNA) sequences presents special problems, which we resolve here with a general solution for the analysis of mtDNA in next-generation sequencing studies. The new program package comprises 1) an algorithm designed to identify mtDNA variants (i.e., homoplasmies and heteroplasmies), incorporating sequencing error rates at each base in a likelihood calculation and allowing allele fractions at a variant site to differ across individuals; and 2) an estimation of mtDNA copy number in a cell directly from whole-genome sequencing data. We also apply the methods to DNA sequence from lymphocytes of similar to 2,000 SardiNIA Project participants. As expected, mothers and offspring share all homoplasmies but a lesser proportion of heteroplasmies. Both homoplasmies and heteroplasmies show 5-fold higher transition/transversion ratios than variants in nuclear DNA. Also, heteroplasmy increases with age, though on average only similar to 1 heteroplasmy reaches the 4% level between ages 20 and 90. In addition, we find that mtDNA copy number averages similar to 110 copies/lymphocyte and is similar to 54% heritable, implying substantial genetic regulation of the level of mtDNA. Copy numbers also decrease modestly but significantly with age, and females on average have significantly more copies than males. The mtDNA copy numbers are significantly associated with waist circumference (p-value = 0.0031) and waist-hip ratio (p-value = 2.4x10(-5)), but not with body mass index, indicating an association with central fat distribution. To our knowledge, this is the largest population analysis to date of mtDNA dynamics, revealing the age-imposed increase in heteroplasmy, the relatively high heritability of copy number, and the association of copy number with metabolic traits.
C1 [Ding, Jun; Butler, Thomas J.; Qian, Yong; Meirelles, Osorio; Nagaraja, Ramaiah; Schlessinger, David] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA.
[Sidore, Carlo; Wing, Mary Kate; Busonero, Fabio; Tsoi, Lam C.; Maschio, Andrea; Kang, Hyun Min; Abecasis, Goncalo R.] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
[Sidore, Carlo; Wing, Mary Kate; Busonero, Fabio; Tsoi, Lam C.; Maschio, Andrea; Kang, Hyun Min; Abecasis, Goncalo R.] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Sidore, Carlo; Busonero, Fabio; Maschio, Andrea; Angius, Andrea; Cucca, Francesco] CNR, Ist Ric Genet & Biomed, Cagliari, Italy.
[Sidore, Carlo; Cucca, Francesco] Univ Sassari, I-07100 Sassari, Italy.
RP Ding, J (reprint author), NIA, Genet Lab, NIH, Baltimore, MD 21224 USA.
EM jun.ding@nih.gov; SchlessingerD@grc.nia.nih.gov
RI Angius, Andrea/P-9549-2015;
OI Angius, Andrea/0000-0003-2596-6461; Tsoi, Lam Cheung/0000-0003-1627-5722
FU National Institutes of Health (National Institute on Aging, National
Heart Lung and Blood Institute, and National Human Genome Research
Institute); National Human Genome Research Institute [HG005581,
HG005552, HG006513, HG007089, HG007022]; National Heart Lung and Blood
Institute [HL117626]; Intramural Research Program of the NIH, National
Institute on Aging [N01-AG-1-2109, HHSN271201100005C]; Sardinian
Autonomous Region [cRP3-154]
FX This study was funded in part by the National Institutes of Health
(National Institute on Aging, National Heart Lung and Blood Institute,
and National Human Genome Research Institute). This research was
supported by National Human Genome Research Institute grants HG005581,
HG005552, HG006513, HG007089, HG007022, and HG007089; by National Heart
Lung and Blood Institute grant HL117626; by the Intramural Research
Program of the NIH, National Institute on Aging, with contracts
N01-AG-1-2109 and HHSN271201100005C; and by Sardinian Autonomous Region
(L.R. no. 7/2009) grant cRP3-154. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 28
TC 8
Z9 8
U1 2
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD JUL
PY 2015
VL 11
IS 7
AR e1005306
DI 10.1371/journal.pgen.1005306
PG 18
WC Genetics & Heredity
SC Genetics & Heredity
GA CQ5CZ
UT WOS:000360622200008
PM 26172475
ER
PT J
AU Karlitz, JJ
Hsieh, MC
Liu, Y
Blanton, C
Schmidt, B
Jessup, JM
Wu, XC
Chen, VW
AF Karlitz, Jordan J.
Hsieh, Mei-Chin
Liu, Yong
Blanton, Christine
Schmidt, Beth
Jessup, J. Milburn
Wu, Xiao-Cheng
Chen, Vivien W.
TI Population-Based Lynch Syndrome Screening by Microsatellite Instability
in Patients <= 50: Prevalence, Testing Determinants, and Result
Availability Prior to Colon Surgery
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Article
ID NONPOLYPOSIS COLORECTAL-CANCER; YOUNG-PATIENTS; BRAF MUTATION;
HEREDITARY; IMMUNOHISTOCHEMISTRY; RISK; UNDERUTILIZATION; CARRIERS;
TUMORS; ONSET
AB OBJECTIVES: As there are no US population-based studies examining Lynch syndrome (LS) screening frequency by microsatellite instability (MSI) and immunohistochemistry (IHC), we seek to quantitate statewide rates in patients aged <= 50 years using data from a Centers for Disease Control and Prevention-funded Comparative Effectiveness Research (CER) project and identify factors associated with testing. Screening rates in this young, high-risk population may provide a best-case scenario as older patients, potentially deemed lower risk, may undergo testing less frequently. We also seek to determine how frequently MSI/IHC results are available preoperatively, as this may assist with decisions regarding colonic resection extent.
METHODS: Data from all Louisiana colorectal cancer (CRC) patients aged <= 50 years diagnosed in 2011 were obtained from the Louisiana Tumor Registry CER project. Registry researchers and physicians analyzed data, including pathology and MSI/IHC.
RESULTS: Of the 2,427 statewide all-age CRC patients, there were 274 patients aged <= 50 years, representing health care at 61 distinct facilities. MSI and/or IHC were performed in 23.0% of patients. Testing-associated factors included CRC family history (P<0.0045), urban location (P<0.0370), and care at comprehensive cancer centers (P<0.0020) but not synchronous/metachronous CRC or MSI-like histology. Public hospital screening was disproportionately low (P<0.0217). Of those tested, MSI and/or IHC was abnormal in 21.7%. Of those with abnormal IHC, staining patterns were consistent with LS in 87.5%. MSI/IHC results were available preoperatively in 16.9% of cases.
CONCLUSIONS: Despite frequently abnormal MSI/IHC results, LS screening in young, high-risk patients is low. Provider education and disparities in access to specialized services, particularly in underserved populations, are possible contributors. MSI/IHC results are infrequently available preoperatively.
C1 [Karlitz, Jordan J.; Blanton, Christine] Tulane Univ, Sch Med, Div Gastroenterol, New Orleans, LA 70112 USA.
[Hsieh, Mei-Chin; Wu, Xiao-Cheng; Chen, Vivien W.] LSU Hlth Sci Ctr, Sch Publ Hlth, Program Epidemiol, Louisiana Tumor Registry, New Orleans, LA USA.
[Liu, Yong] Tulane Univ, Sch Med, Dept Med, New Orleans, LA 70112 USA.
[Schmidt, Beth] LSU Hlth Sci Ctr, Sch Publ Hlth, Louisiana Tumor Registry, New Orleans, LA USA.
[Jessup, J. Milburn] NCI, Canc Diag Program, Div Canc Treatment & Diag, NIH, Rockville, MD USA.
RP Karlitz, JJ (reprint author), Tulane Univ, Sch Med, Dept Med, Div Gastroenterol, 1430 Tulane Ave,SL 35, New Orleans, LA 70112 USA.
EM jkarlitz@tulane.edu
FU CDC Cooperative Agreements of the National Program of Cancer
[U58DP003915]; CDC/ICF Comparative Effectiveness Research
[635243-10S-1566]; LSUHSC-NO
FX Financial support: This work was supported in part under the CDC
Cooperative Agreements of the National Program of Cancer Registries:
#U58DP003915 and CDC/ICF Comparative Effectiveness Research subcontract:
#635243-10S-1566 with LSUHSC-NO.
NR 25
TC 10
Z9 10
U1 1
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0002-9270
EI 1572-0241
J9 AM J GASTROENTEROL
JI Am. J. Gastroenterol.
PD JUL
PY 2015
VL 110
IS 7
BP 948
EP 955
DI 10.1038/ajg.2014.417
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CP9FV
UT WOS:000360200100001
PM 25601013
ER
PT J
AU Drevinge, C
Dalen, KT
Mannila, MN
Scharin-Tang, M
Stahlman, M
Lundqvist, A
Klevstig, M
Redfors, B
Gan, LM
Andersson, L
Ehrenborg, E
Kimmel, A
Boren, J
Levin, MC
AF Drevinge, C.
Dalen, K. T.
Mannila, M. N.
Scharin-Tang, M.
Stahlman, M.
Lundqvist, A.
Klevstig, M.
Redfors, B.
Gan, L. M.
Andersson, L.
Ehrenborg, E.
Kimmel, A.
Boren, J.
Levin, M. C.
TI PERILIPIN 5 IS PROTECTIVE IN THE ISCHEMIC HEART
SO ATHEROSCLEROSIS
LA English
DT Meeting Abstract
CT 83rd Congress of the European-Atherosclerosis-Society (EAS)
CY MAR 22-25, 2015
CL Glasgow, SCOTLAND
SP European Atherosclerosis Soc
C1 [Drevinge, C.; Stahlman, M.; Lundqvist, A.; Klevstig, M.; Redfors, B.; Gan, L. M.; Andersson, L.; Boren, J.; Levin, M. C.] Univ Gothenburg, Inst Med, Sahlgrenska Acad, Dept Mol & Clin Med, Gothenburg, Sweden.
[Dalen, K. T.] Univ Oslo, Inst Basic Med Sci, Dept Nutr, Oslo, Norway.
[Mannila, M. N.; Scharin-Tang, M.; Ehrenborg, E.] Karolinska Univ Hosp, Ctr Mol Med, Atherosclerosis Res Unit, Stockholm, Sweden.
[Kimmel, A.] NIDDKD, Lab Cellular & Dev Biol, NIH, Bethesda, MD USA.
RI Dalen, Knut Tomas/C-4719-2016
OI Dalen, Knut Tomas/0000-0002-0270-5982
NR 0
TC 0
Z9 0
U1 1
U2 2
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0021-9150
EI 1879-1484
J9 ATHEROSCLEROSIS
JI Atherosclerosis
PD JUL
PY 2015
VL 241
IS 1
MA EAS-0768
BP E12
EP E13
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA CP7WS
UT WOS:000360100600042
ER
PT J
AU Grivel, JC
Arakelyan, A
Vagida, M
Lebedeva, A
Ivanova, O
Nikitskaya, E
Ryazankina, N
Shpektor, A
Margolis, L
Vasilieva, E
AF Grivel, J. C.
Arakelyan, A.
Vagida, M.
Lebedeva, A.
Ivanova, O.
Nikitskaya, E.
Ryazankina, N.
Shpektor, A.
Margolis, L.
Vasilieva, E.
TI INDIVIDUAL EXTRACELLULAR VESICLES IN PATIENTS WITH ACUTE CORONARY
SYNDROMES
SO ATHEROSCLEROSIS
LA English
DT Meeting Abstract
CT 83rd Congress of the European-Atherosclerosis-Society (EAS)
CY MAR 22-25, 2015
CL Glasgow, SCOTLAND
SP European Atherosclerosis Soc
C1 [Grivel, J. C.; Arakelyan, A.; Margolis, L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD USA.
[Vagida, M.; Lebedeva, A.; Ivanova, O.; Nikitskaya, E.; Ryazankina, N.; Shpektor, A.; Vasilieva, E.] Moscow State Univ Med & Dent AI Evdokimov, Lab Atherothombosis, Moscow, Russia.
RI Shpektor, Alexander/B-1083-2016; Vasilieva, Elena/B-2137-2016
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0021-9150
EI 1879-1484
J9 ATHEROSCLEROSIS
JI Atherosclerosis
PD JUL
PY 2015
VL 241
IS 1
MA EAS-0542
BP E39
EP E40
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA CP7WS
UT WOS:000360100600123
ER
PT J
AU Nikitskaya, E
Ivanova, O
Maryukhnich, E
Grivel, JC
Lebedeva, A
Shpektor, A
Margolis, L
Vasilieva, E
AF Nikitskaya, E.
Ivanova, O.
Maryukhnich, E.
Grivel, J. C.
Lebedeva, A.
Shpektor, A.
Margolis, L.
Vasilieva, E.
TI HUMAN HERPES VIRUS DNA DISTRIBUTION IN PATIENTS WITH ACUTE CORONARY
SYNDROME
SO ATHEROSCLEROSIS
LA English
DT Meeting Abstract
CT 83rd Congress of the European-Atherosclerosis-Society (EAS)
CY MAR 22-25, 2015
CL Glasgow, SCOTLAND
SP European Atherosclerosis Soc
C1 [Nikitskaya, E.; Ivanova, O.; Maryukhnich, E.; Lebedeva, A.; Shpektor, A.; Vasilieva, E.] Moscow State Univ Med & Dent, Cardiol, Moscow, Russia.
[Grivel, J. C.; Margolis, L.] NICHD, Program Phys Biol, NIH, Bethesda, MD USA.
RI Shpektor, Alexander/B-1083-2016; Vasilieva, Elena/B-2137-2016
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0021-9150
EI 1879-1484
J9 ATHEROSCLEROSIS
JI Atherosclerosis
PD JUL
PY 2015
VL 241
IS 1
MA EAS-0797
BP E178
EP E178
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA CP7WS
UT WOS:000360100600588
ER
PT J
AU Ossoli, A
Neufeld, E
Amar, M
Vitali, C
Thacker, S
Locatelli, M
Abbate, M
Pryor, M
Zoja, C
Calabresi, L
Remaley, AT
AF Ossoli, A.
Neufeld, E.
Amar, M.
Vitali, C.
Thacker, S.
Locatelli, M.
Abbate, M.
Pryor, M.
Zoja, C.
Calabresi, L.
Remaley, A. T.
TI ROLE OF LPX IN THE DEVELOPMENT OF RENAL DISEASE IN LCAT DEFICIENCY
SO ATHEROSCLEROSIS
LA English
DT Meeting Abstract
CT 83rd Congress of the European-Atherosclerosis-Society (EAS)
CY MAR 22-25, 2015
CL Glasgow, SCOTLAND
SP European Atherosclerosis Soc
C1 [Ossoli, A.; Vitali, C.; Calabresi, L.] Univ Milan, Dept Pharmacol & Biomol Sci, Milan, Italy.
[Neufeld, E.; Amar, M.; Thacker, S.; Pryor, M.; Remaley, A. T.] NHLBI, Lipoprot Metab Sect, NIH, Bethesda, MD 20892 USA.
[Locatelli, M.; Abbate, M.; Zoja, C.] IRCCS Ist Ric Farmacol Mario Negri, Ctr Anna Maria Astori, Bergamo, Italy.
RI Ossoli, Alice/K-5917-2016
OI Ossoli, Alice/0000-0002-9902-252X
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 0021-9150
EI 1879-1484
J9 ATHEROSCLEROSIS
JI Atherosclerosis
PD JUL
PY 2015
VL 241
IS 1
MA EAS-0490
BP E65
EP E65
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA CP7WS
UT WOS:000360100600209
ER
PT J
AU Ossoli, A
Remaley, AT
Vaisman, B
Calabresi, L
Gomaraschi, M
AF Ossoli, A.
Remaley, A. T.
Vaisman, B.
Calabresi, L.
Gomaraschi, M.
TI PLASMA-DERIVED AND SYNTHETIC HDL INHIBIT TISSUE FACTOR IN ENDOTHELIAL
CELLS AND MONOCYTES: MECHANISMS AND IN VIVO RELEVANCE
SO ATHEROSCLEROSIS
LA English
DT Meeting Abstract
CT 83rd Congress of the European-Atherosclerosis-Society (EAS)
CY MAR 22-25, 2015
CL Glasgow, SCOTLAND
SP European Atherosclerosis Soc
C1 [Ossoli, A.; Calabresi, L.; Gomaraschi, M.] Univ Milan, Dipartimento Sci Farmacol & Biomol, Milan, Italy.
[Remaley, A. T.; Vaisman, B.] NHLBI, Lipoprot Metab Sect, NIH, Bethesda, MD 20892 USA.
RI Ossoli, Alice/K-5917-2016
OI Ossoli, Alice/0000-0002-9902-252X
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 0021-9150
EI 1879-1484
J9 ATHEROSCLEROSIS
JI Atherosclerosis
PD JUL
PY 2015
VL 241
IS 1
MA EAS-0350
BP E29
EP E29
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA CP7WS
UT WOS:000360100600091
ER
PT J
AU Alqahtani, SA
Kleiner, DE
Ghabril, M
Gu, JZ
Hoofnagle, JH
Rockey, DC
AF Alqahtani, Saleh A.
Kleiner, David E.
Ghabril, Marwan
Gu, Jiezhun
Hoofnagle, Jay H.
Rockey, Don C.
CA Drug-Induced Liver Injury Network
TI Identification and Characterization of Cefazolin-Induced Liver Injury
SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
LA English
DT Article
DE Hepatotoxicity; DILIN; Antibiotic; Cephalosporin
ID INDUCED HEPATOTOXICITY; CHOLESTATIC HEPATITIS; UNITED-STATES; DRUG;
CEFTRIAXONE; CEPHALOSPORINS; INFECTION; OUTCOMES; THERAPY; RATIONALE
AB BACKGROUND & AIMS: Cephalosporin antibiotics are popular because they have a broad spectrum of activity and are generally well tolerated; however, cephalosporin-induced liver injury is considered rare. We describe a new syndrome associated with a single intravenous dose of cefazolin and the clinical features of cephalosporin-induced liver injury.
METHODS: The Drug-Induced Liver Injury (DILI) Network collected detailed clinical data on 1212 patients with DILI between 2004 and 2012. We analyzed data from 41 patients in whom cephalosporins were implicated as primary agents of liver disease; 33 formally were adjudicated as having cephalosporin-induced DILI.
RESULTS:Nineteen patients developed clinically apparent DILI after a single intravenous dose of cefazolin. All patients developed self-limited liver injury 3 to 23 days after receiving cefazolin during surgery often during a minor outpatient procedure. The latency period was 20 days. Clinical features included itching, jaundice, nausea, fever, and rash. Laboratory abnormalities included a mixed or cholestatic pattern of serum enzyme increases. We identified 14 more patients with DILI attributed to other cephalosporins (5 first-generation, 2 second-generation, 6 third-generation, and 1 fourth-generation agent). Although latency and injury patterns were similar for cefazolin and other cephalosporins, the other cephalosporins were associated with more severe courses of injury, including 2 deaths from liver failure.
CONCLUSIONS: DILI can develop after a single dose of cefazolin. It is characterized by a latency period of 1 to 3 weeks after exposure, a cholestatic biochemical pattern, and a self-limited moderate to severe clinical course. Other cephalosporins can cause a similar but more severe injury.
C1 [Alqahtani, Saleh A.; Rockey, Don C.] Univ Texas Southwestern, Div Digest & Liver Dis, Dallas, TX USA.
[Kleiner, David E.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Hoofnagle, Jay H.] NIDDK, Liver Dis Res Branch, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA.
[Ghabril, Marwan] Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA.
[Gu, Jiezhun] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA.
RP Rockey, DC (reprint author), Med Univ S Carolina, Dept Med, 96 Jonathan Lucas St, Charleston, SC 29425 USA.
EM rockey@musc.edu
OI Ghabril, Marwan/0000-0002-4784-3246
FU National Institute of Diabetes and Digestive and Kidney Diseases
[2U01-DK065176-06, 2U01- DK065201-06, 2U01-DK065184-06,
2U01-DK065211-06, 5U01DK065193-04, 5U01-DK065238-08, 1U01-DK083023-01,
1U01-DK083027-01, 1U01- DK082992-01, 1U01-DK083020-01]; Intramural
Research Program of the National Institutes of Health, National Cancer
Institute; [UL1 RR025761]; [UL1 RR025747]; [UL1 RR024134]; [UL1
RR024986]; [UL1 RR024982]; [UL1 RR024150]
FX The Drug-Induced Liver Injury Network is structured as a U01 cooperative
agreement with funds provided by the National Institute of Diabetes and
Digestive and Kidney Diseases from the following grants:
2U01-DK065176-06 (Duke University Medical Center), 2U01- DK065201-06
(University of North Carolina [Chapel Hill]), 2U01-DK065184-06
(University of Michigan), 2U01-DK065211-06 (Indiana University),
5U01DK065193-04 (University of Connecticut), 5U01-DK065238-08
(University of California, San Francisco/California Pacific Medical
Center), 1U01-DK083023-01 (University of Texas Southwestern),
1U01-DK083027-01 (Thomas Jefferson University Hospital, University of
Pennsylvania), 1U01- DK082992-01 (Mayo Clinic), and 1U01-DK083020-01
(University of Southern California). Additional funding was provided by
the following Clinical and Translational Science Award grants: UL1
RR025761 (Indiana University), UL1 RR025747 (University of North
Carolina [Chapel Hill]), UL1 RR024134 (University of Pennsylvania), UL1
RR024986 (University of Michigan), UL1 RR024982 (University of Texas
Southwestern), and UL1 RR024150 (Mayo Clinic), and in part by the
Intramural Research Program of the National Institutes of Health,
National Cancer Institute.
NR 32
TC 4
Z9 5
U1 3
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1542-3565
EI 1542-7714
J9 CLIN GASTROENTEROL H
JI Clin. Gastroenterol. Hepatol.
PD JUL
PY 2015
VL 13
IS 7
BP 1328
EP +
DI 10.1016/j.cgh.2014.11.036
PG 11
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CP7FY
UT WOS:000360053800134
PM 25528012
ER
PT J
AU Clay, JR
AF Clay, John R.
TI Novel description of ionic currents recorded with the action potential
clamp technique: application to excitatory currents in suprachiasmatic
nucleus neurons
SO JOURNAL OF NEUROPHYSIOLOGY
LA English
DT Article
DE action potential clamp; suprachiasmatic nucleus neurons; mathematical
models; Goldman-Hodgkin-Katz
ID EFFICIENT ACTION-POTENTIALS; MAMMALIAN CENTRAL NEURONS; PERSISTENT
SODIUM CURRENT; SQUID GIANT-AXON; DYNAMIC CLAMP; POTASSIUM CURRENT;
GATING CURRENTS; CALCIUM CURRENT; SINGLE-CHANNEL; MODEL
AB The traditional method of recording ionic currents in neurons has been with voltage-clamp steps. Other waveforms such as action potentials (APs) can be used. The AP clamp method reveals contributions of ionic currents that underlie excitability during an AP (Bean BP. Nat Rev Neurosci 8: 451-465, 2007). A novel usage of the method is described in this report. An experimental recording of an AP from the literature is digitized and applied computationally to models of ionic currents. These results are compared with experimental AP-clamp recordings for model verification or, if need be, alterations to the model. The method is applied to the tetrodotoxin-sensitive sodium ion current, I-Na, and the calcium ion current, I-Ca, from suprachiasmatic nucleus (SCN) neurons (Jackson AC, Yao GL, Bean BP. J Neurosci 24: 7985-7998, 2004). The latter group reported voltage-step and AP-clamp results for both components. A model of I-Na is constructed from their voltage-step results. The AP clamp computational methodology applied to that model compares favorably with experiment, other than a modest discrepancy close to the peak of the AP that has not yet been resolved. A model of I-Ca was constructed from both voltage-step and AP-clamp results of this component. The model employs the Goldman-Hodgkin-Katz equation for the current-voltage relation rather than the traditional linear dependence of this aspect of the model on the Ca2+ driving force. The long-term goal of this work is a mathematical model of the SCN AP. The method is general. It can be applied to any excitable cell.
C1 [Clay, John R.] NINDS, NIH, Bethesda, MD 20892 USA.
RP Clay, JR (reprint author), Twinbrook 4S-26,5625 Fishers Ln, Rockville, MD 20852 USA.
EM jrclay@ninds.nih.gov
FU National Institute of Neurological Disorders and Stroke, National
Institutes of Health, Bethesda, MD
FX This research was supported by the Intramural Research Program of the
National Institute of Neurological Disorders and Stroke, National
Institutes of Health, Bethesda, MD.
NR 57
TC 1
Z9 1
U1 1
U2 4
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3077
EI 1522-1598
J9 J NEUROPHYSIOL
JI J. Neurophysiol.
PD JUL 1
PY 2015
VL 114
IS 1
BP 707
EP 716
DI 10.1152/jn.00846.2014
PG 10
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA CQ4EH
UT WOS:000360556600027
PM 26041831
ER
PT J
AU Colvis, CM
Austin, CP
AF Colvis, Christine M.
Austin, Christopher P.
TI The NIH-Industry New Therapeutic Uses Pilot Program: Demonstrating the
Power of Crowdsourcing
SO ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES
LA English
DT Review
ID SARACATINIB; INHIBITOR
C1 [Colvis, Christine M.; Austin, Christopher P.] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
RP Colvis, CM (reprint author), NIH, Natl Ctr Adv Translat Sci, 6701 Democracy Blvd,,Democracy 1,Room 994, Bethesda, MD 20892 USA.
EM ccolvis@mail.nih.gov
NR 4
TC 0
Z9 0
U1 2
U2 2
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-658X
EI 1557-8127
J9 ASSAY DRUG DEV TECHN
JI ASSAY DRUG DEV. TECHNOL.
PD JUL 1
PY 2015
VL 13
IS 6
BP 297
EP 298
DI 10.1089/adt.2015.29006.cmcdrrr
PG 2
WC Biochemical Research Methods; Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA CP4GL
UT WOS:000359839900003
PM 26241208
ER
PT J
AU Kuhn, NZ
Woodhouse, EC
Mohla, S
AF Kuhn, Nastaran Z.
Woodhouse, Elisa C.
Mohla, Suresh
TI The National Cancer Institute's Efforts in Promoting Research in the
Tumor Microenvironment
SO CANCER JOURNAL
LA English
DT Review
DE Epithelial-to-mesenchymal transition; extracellular vesicles; exosomes;
microparticles; oncosomes; extracellular matrix; mechanics; stromal
cells; technology; tumor dormancy; tumor microenvironment
ID EPITHELIAL-MESENCHYMAL TRANSITION; PROSTATE-CANCER; BREAST-CANCER;
COLORECTAL-CANCER; PERINEURAL INVASION; ORGANOID CULTURES; SINGLE CELLS;
IDENTIFICATION; PROGRESSION; METASTASIS
AB The National Cancer Institute has fostered studies of the tumor microenvironment since 1993. Current funding initiatives that span concepts in cancer biology, technology development, convergence of physical sciences-oncology, and systems biology all support research that help in our understanding of the role of the tumor microenvironment at all stages of cancer progression and therapeutic resistance.
C1 [Kuhn, Nastaran Z.; Woodhouse, Elisa C.; Mohla, Suresh] NCI, NIH, Div Canc Biol, Rockville, MD 20850 USA.
RP Mohla, S (reprint author), NCI, NIH, 9609 Med Ctr Dr, Rockville, MD 20850 USA.
EM mohlas@mail.nih.gov
NR 50
TC 0
Z9 0
U1 1
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1528-9117
EI 1540-336X
J9 CANCER J
JI Cancer J.
PD JUL-AUG
PY 2015
VL 21
IS 4
BP 263
EP 266
DI 10.1097/PPO.0000000000000130
PG 4
WC Oncology
SC Oncology
GA CP3YY
UT WOS:000359820200006
PM 26222077
ER
PT J
AU Sokolov, M
Nguyen, V
Neumann, R
AF Sokolov, Mykyta
Van Nguyen
Neumann, Ronald
TI Comparative Analysis of Whole- Genome Gene Expression Changes in
Cultured Human Embryonic Stem Cells in Response to Low, Clinical
Diagnostic Relevant, and High Doses of Ionizing Radiation Exposure
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE whole genome; human embryonic stem cell; ionizing radiation; DNA
microarray; low dose exposure
ID NORMAL HUMAN FIBROBLASTS; DNA-DAMAGE; TRANSCRIPTIONAL RESPONSE;
MICROARRAY ANALYSIS; SELF-RENEWAL; STRESS GENES; GAMMA-RAYS;
BIODOSIMETRY; PLURIPOTENCY; PERSPECTIVE
AB The biological effects of low-dose ionizing radiation (LDIR) exposure in humans are not comprehensively understood, generating a high degree of controversy in published literature. The earliest stages of human development are known to be among the most sensitive to stress exposures, especially genotoxic stresses. However, the risks stemming from exposure to LDIR, particularly within the clinical diagnostic relevant dose range, have not been directly evaluated in human embryonic stem cells (hESCs). Here, we describe the dynamics of the whole genome transcriptional responses of different hESC lines to both LDIR and, as a reference, high-dose IR (HDIR). We found that even doses as low as 0.05 Gy could trigger statistically significant transient changes in a rather limited subset of genes in all hESCs lines examined. Gene expression signatures of hESCs exposed to IR appear to be highly dose-, time-, and cell line-dependent. We identified 50 genes constituting consensus gene expression signature as an early response to HDIR across all lines of hESC examined. We observed substantial differences in biological pathways affected by either LDIR or HDIR in hESCs, suggesting that the molecular mechanisms underpinning the responses of hESC may fundamentally differ depending on radiation doses.
C1 [Sokolov, Mykyta; Van Nguyen; Neumann, Ronald] NIH, Div Nucl Med, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
RP Sokolov, M (reprint author), NIH, Div Nucl Med, Dept Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
EM sokolovm@mail.nih.gov; van.nguyen3@nih.gov; rneumann@mail.nih.gov
FU National Institutes of Health, Clinical Center
FX We wish to thank William DeGraff for his invaluable help with cell
culture irradiation. This work was supported by the Intramural Research
Program of the National Institutes of Health, Clinical Center.
NR 40
TC 3
Z9 3
U1 1
U2 3
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1422-0067
J9 INT J MOL SCI
JI Int. J. Mol. Sci.
PD JUL
PY 2015
VL 16
IS 7
BP 14737
EP 14748
DI 10.3390/ijms160714737
PG 12
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
SC Biochemistry & Molecular Biology; Chemistry
GA CP5CY
UT WOS:000359900100028
PM 26133243
ER
PT J
AU Rosenberg, HF
AF Rosenberg, Helene F.
TI Eosinophil-Derived Neurotoxin (EDN/RNase 2) and the Mouse
Eosinophil-Associated RNases (mEars): Expanding Roles in Promoting Host
Defense
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Review
DE inflammation; leukocyte; evolution; chemoattractant
ID RIBONUCLEASE-A SUPERFAMILY; RESPIRATORY SYNCYTIAL VIRUS; INFECTION
IN-VIVO; CATIONIC PROTEIN; GRANULE PROTEINS; GENE FAMILY; DIFFERENTIAL
ACTIVATION; TARGETED RIBONUCLEASE; SCHISTOSOMA-MANSONI; RAPID EVOLUTION
AB The eosinophil-derived neurotoxin (EDN/RNase2) and its divergent orthologs, the mouse eosinophil-associated RNases (mEars), are prominent secretory proteins of eosinophilic leukocytes and are all members of the larger family of RNase A-type ribonucleases. While EDN has broad antiviral activity, targeting RNA viruses via mechanisms that may require enzymatic activity, more recent studies have elucidated how these RNases may generate host defense via roles in promoting leukocyte activation, maturation, and chemotaxis. This review provides an update on recent discoveries, and highlights the versatility of this family in promoting innate immunity.
C1 NIAID, Inflammat Immunobiol Sect, NIH, Bethesda, MD 20892 USA.
RP Rosenberg, HF (reprint author), NIAID, Inflammat Immunobiol Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM hrosenberg@niaid.nih.gov
FU NIAID Division of Intramural Research [AI000941, AI000942, AI000943]
FX This work was supported in by NIAID Division of Intramural Research
funding AI000941, AI000942 and AI000943.
NR 75
TC 4
Z9 4
U1 1
U2 1
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1422-0067
J9 INT J MOL SCI
JI Int. J. Mol. Sci.
PD JUL
PY 2015
VL 16
IS 7
BP 15442
EP 15455
DI 10.3390/ijms160715442
PG 14
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
SC Biochemistry & Molecular Biology; Chemistry
GA CP5CY
UT WOS:000359900100066
PM 26184157
ER
PT J
AU Murase, S
AF Murase, Sachiko
TI Impaired Focal Adhesion Kinase-Grb2 Interaction during Elevated Activity
in Hippocampal Neurons
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE focal adhesion kinase (FAK); Grb2; Erk1/2; signal transducer and
activator of transcription 3 (STAT3); integrin 1;
matrix-metalloproteinase (MMP); excitatory; inhibitory (E; I) balance;
survival signaling
ID LONG-TERM POTENTIATION; MATRIX METALLOPROTEINASES; NEWBORN HIPPOCAMPUS;
SYNAPTIC PLASTICITY; TYROSINE KINASES; RAS PATHWAY; CLEAVAGE;
MATRIX-METALLOPROTEINASE-9; PP125(FAK); ACTIVATION
AB Excitatory/inhibitory imbalances are implicated in many neurological disorders. Previously, we showed that chronically elevated network activity induces vulnerability in neurons due to loss of signal transducer and activator of transcription 3 (STAT3) signaling in response to the impairment of the serine/threonine kinase, extracellular-signal-regulated kinases 1/2 (Erk1/2) activation. However, how phosphorylation of Erk1/2 decreases during elevated neuronal activity was unknown. Here I show the pErk1/2 decrease induced by 4-aminopyridine (4-AP), an A-type potassium channel inhibitor can be blocked by a broad-spectrum matrix-metalloproteinase (MMP) inhibitor, FN-439. Surface expression levels of integrin 1 dramatically decrease when neurons are challenged by chronically elevated activity, which is reversed by FN-439. Treatment with 4-AP induces degradation of focal adhesion kinase (FAK), the mediator of integrin signaling. As a result, interactions between FAK and growth factor receptor-bound protein 2 (Grb2), the adaptor protein that mediates Erk1/2 activation by integrin, are severely impaired. Together, these data suggest the loss of integrin signaling during elevated activity causes vulnerability in neurons.
C1 [Murase, Sachiko] NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Murase, Sachiko] Univ Maryland, Dept Biol & Neurosci, College Pk, MD 20742 USA.
[Murase, Sachiko] Univ Maryland, Cognit Sci Program, College Pk, MD 20742 USA.
RP Murase, S (reprint author), NINDS, Mol Biol Lab, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM smurase@umd.edu
FU NINDS/NIH
FX This work was supported by the Intramural Research Program of the
NINDS/NIH.
NR 42
TC 0
Z9 0
U1 0
U2 2
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1422-0067
J9 INT J MOL SCI
JI Int. J. Mol. Sci.
PD JUL
PY 2015
VL 16
IS 7
BP 15659
EP 15669
DI 10.3390/ijms160715659
PG 11
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
SC Biochemistry & Molecular Biology; Chemistry
GA CP5CY
UT WOS:000359900100077
PM 26184168
ER
PT J
AU Gunduz, A
Morita, H
Rossi, PJ
Allen, WL
Alterman, RL
Bronte-Stewart, H
Butson, CR
Charles, D
Deckers, S
de Hemptinne, C
DeLong, M
Dougherty, D
Ellrich, J
Foote, KD
Giordano, J
Goodman, W
Greenberg, BD
Greene, D
Gross, R
Judy, JW
Karst, E
Kent, A
Kopell, B
Lang, A
Lozano, A
Lungu, C
Lyon, KE
Machado, A
Martens, H
McIntyre, C
Min, HK
Neimat, J
Ostrem, J
Pannu, S
Ponce, F
Pouratian, N
Reymers, D
Schrock, L
Sheth, S
Shih, L
Stanslaski, S
Steinke, GK
Stypulkowski, P
Troster, AI
Verhagen, L
Walker, H
Okun, MS
AF Gunduz, Aysegul
Morita, Hokuto
Rossi, P. Justin
Allen, William L.
Alterman, Ron L.
Bronte-Stewart, Helen
Butson, Christopher R.
Charles, David
Deckers, Sjaak
de Hemptinne, Coralie
DeLong, Mahlon
Dougherty, Darin
Ellrich, Jens
Foote, Kelly D.
Giordano, James
Goodman, Wayne
Greenberg, Benjamin D.
Greene, David
Gross, Robert
Judy, Jack W.
Karst, Edward
Kent, Alexander
Kopell, Brian
Lang, Anthony
Lozano, Andres
Lungu, Codrin
Lyon, Kelly E.
Machado, Andre
Martens, Hubert
McIntyre, Cameron
Min, Hoon-Ki
Neimat, Joseph
Ostrem, Jill
Pannu, Sat
Ponce, Francisco
Pouratian, Nader
Reymers, Donnie
Schrock, Lauren
Sheth, Sameer
Shih, Ludy
Stanslaski, Scott
Steinke, G. Karl
Stypulkowski, Paul
Troester, Alexander I.
Verhagen, Leo
Walker, Harrison
Okun, Michael S.
TI Proceedings of the Second Annual Deep Brain Stimulation Think Tank:
What's in the Pipeline
SO INTERNATIONAL JOURNAL OF NEUROSCIENCE
LA English
DT Review
DE deep brain stimulation; Movement disorders; Neuroethics;
Electrophysiology; neurotechnology
ID HIGH-FREQUENCY STIMULATION; HUMAN SUBTHALAMIC NUCLEUS; SHORT-LATENCY
ACTIVATION; PRIMARY MOTOR CORTEX; PARKINSONS-DISEASE; NONMOTOR SYMPTOMS;
GLOBUS-PALLIDUS; THALAMIC SEGMENTATION; CLINICAL ARTICLE; BOLD
ACTIVATION
AB The proceedings of the 2nd Annual Deep Brain Stimulation Think Tank summarize the most contemporary clinical, electrophysiological, and computational work on DBS for the treatment of neurological and neuropsychiatric disease and represent the insights of a unique multidisciplinary ensemble of expert neurologists, neurosurgeons, neuropsychologists, psychiatrists, scientists, engineers and members of industry. Presentations and discussions covered a broad range of topics, including advocacy for DBS, improving clinical outcomes, innovations in computational models of DBS, understanding of the neurophysiology of Parkinson's disease (PD) and Tourette syndrome (TS) and evolving sensor and device technologies.
C1 [Gunduz, Aysegul; Morita, Hokuto; Rossi, P. Justin; Allen, William L.; Foote, Kelly D.; Judy, Jack W.; Okun, Michael S.] Univ Florida, Gainesville, FL USA.
[Alterman, Ron L.; Shih, Ludy] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Bronte-Stewart, Helen] Stanford Univ, Stanford, CA 94305 USA.
[Butson, Christopher R.; Schrock, Lauren] Univ Utah, Salt Lake City, UT USA.
[Charles, David; Neimat, Joseph] Vanderbilt Univ, Nashville, TN 37235 USA.
[Deckers, Sjaak; Ellrich, Jens; Martens, Hubert] Sapiens Steering Brain Stimulat, Eindhoven, Netherlands.
[de Hemptinne, Coralie; Ostrem, Jill] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[DeLong, Mahlon; Gross, Robert] Emory Univ, Atlanta, GA 30322 USA.
[Dougherty, Darin] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Giordano, James] Georgetown Univ, Med Ctr, Washington, DC 20007 USA.
[Goodman, Wayne; Kopell, Brian] Mt Sinai Hosp, New York, NY 10029 USA.
[Greenberg, Benjamin D.] Brown Univ, Providence, RI 02912 USA.
[Greene, David] Neuropace Univ, Mountain View, CA USA.
[Karst, Edward] St Jude Med, Sylmar, CA USA.
[Kent, Alexander] St Jude Med, Sunnyvale, CA USA.
[Lang, Anthony; Lozano, Andres] Univ Toronto, Toronto, ON, Canada.
[Lungu, Codrin] NIH, Bethesda, MD 20892 USA.
[Lyon, Kelly E.] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA.
[Machado, Andre] Cleveland Clin, Cleveland, OH 44106 USA.
[McIntyre, Cameron] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Min, Hoon-Ki] Mayo Clin, Rochester, MN USA.
[Pannu, Sat] Lawrence Livermore Natl Lab, Livermore, CA USA.
[Ponce, Francisco; Troester, Alexander I.] Barrow Neurol Inst, Phoenix, AZ 85013 USA.
[Pouratian, Nader] Univ Calif Los Angeles, Los Angeles, CA USA.
[Reymers, Donnie] Funct Neuromodulat Ltd, Toronto, ON, Canada.
[Sheth, Sameer] Columbia Univ, New York, NY USA.
[Stanslaski, Scott; Stypulkowski, Paul] Medtronic, Minneapolis, MN USA.
[Steinke, G. Karl] Boston Sci Neuromodulat, Valencia, CA USA.
[Verhagen, Leo] Rush Univ, Med Ctr, Chicago, IL 60612 USA.
[Walker, Harrison] Univ Alabama Birmingham, Birmingham, AL USA.
RP Okun, MS (reprint author), Univ Florida, Dept Neurol, Gainesville, FL 32611 USA.
EM okun@neurology.ufl.edu
RI Gunduz, Aysegul/Q-2336-2016;
OI Okun, Michael/0000-0002-6247-9358
FU Medtronic, Inc.; Allergan; Ipsen; Merz; Medtronic; Alliance for Patient
Access for education or consulting services; Cyberonics; Eli Lilly;
Roche; St. Jude; Boston Scientific; Neuropace; Brain Canada; Canadian
Institutes of Health Research; Edmond J Safra Philanthropic Foundation;
Michael J. Fox Foundation; Ontario Brain Institute; National Parkinson
Foundation; Parkinson Society Canada; Tourette Syndrome Association; W.
Garfield Weston Foundation; MRI Interventions; St Jude Medical; Glaxo
Smith Kone; NIH; NPF; Parkinson Alliance; Smallwood Foundation;
Bachmann-Strauss Foundation; UP Foundation
FX AG: Grant support from Medtronic, Inc.; HK: None; PJR: None; WLA: None;
RLA: Consultant for Medtronic, Inc.; HB-S: None; CRB: Consultant for St
Jude Medical, Boston Scientific; IP related to DBS; DC: Vanderbilt
receives income from grants or contracts from Allergan, Ipsen, Merz and
Medtronic for research led by DC; DC receives income from Allergan,
Ipsen, Medtronic and, the Alliance for Patient Access for education or
consulting services; SD: Employee and shareholder of Sapiens Steering
Brain Stimulation GmbH (Medtronic Eindhoven Design Center); CDH: None;
MDL: None; DD: Grant support from Medtronic, Cyberonics, Eli Lilly,
Roche, Honoraria from Medtronic, Insys, Johnson & Johnson; JE: Chief
Medical Officer at Sapiens Steering Brain Stimulation GmbH; KDF: Grant
support from Medtronic, St. Jude, Boston Scientific, Neuropace;
Consultant for Medtronic, Neuropace; JG: None; WG: None; BDG: None; DG:
Employee of Neuropace; RG: None; JJ: None; EK. Employee of St. Jude
Medical; AK: Employee of St. Jude Medical; BK. Consultant for Medtronic,
St Jude Neuromodulation, MRI Interventions; ALang: Consultant for
Abbvie, Allon Therapeutics, Avanir Pharmaceuticals, Biogen Idec,
Boerhinger-Ingelheim, Ceregene, Lilly, Medtronic, Merck, Novartis,
NeuroPhage Pharmaceuticals, Teva, UCB; Honoraria from Medtronic, Teva,
UCB, AbbVie; Grant support from Brain Canada, Canadian Institutes of
Health Research, Edmond J Safra Philanthropic Foundation, Michael J. Fox
Foundation, the Ontario Brain Institute, National Parkinson Foundation,
Parkinson Society Canada, Tourette Syndrome Association, W. Garfield
Weston Foundation; Publishing royalties from Saunders, Wiley-Blackwell,
Johns Hopkins Press, Cambridge University Press; ALozano: Consultant for
Medtronic, St Jude and Boston Scientific, Co-Founder of Functional
Neuromodulation; CL: None; KL: Consultant for Medtronic, St. Jude
Medical; AM: IP in Enspire, ATI, Cardionomics, Grant support from
Medtronic, Inc., Consultant for Functional Neuromodulation, Spinal
Modulation; HM: Employee and shareholder of Sapiens Steering Brain
Stimulation GmbH (Medtronic Eindhoven Design Center); CM: IP in Boston
Scientific Neuromodulation; Consultant for Boston Scientific
Neuromodulation; Shareholder in Autonomic Technologies, Inc.,
Cardionomics, Inc., Neuros Medical, Inc., Surgical Information Sciences,
Inc.; BM: None; HKM: None; JN: Grant support from Medtronic, Inc.;
Consultant for Medtronic, Inc., Montens Inc.; JO: Grant support from
Boston Scientific, MRI Interventions, St Jude Medical, Medtronic; SP:
None; FP: Consultant for Medtronic, Inc; NP: None; DR: Employee of
Neuromodulation, Inc; LSchrock: Site PI for the Boston Scientific
INTREPID DBS trial; SSheth: None; LShih: None; SStanslanski: Employee of
Medtronic, Inc.; GKS: Employee of Boston Scientific Neuromodulation; PS:
Employee of Medtronic, Inc.; AT: Consultant for St Jude Medical, Boston
Scientific, Theravance, Teva; Grant support from Glaxo Smith Kone,
Speaker for Medtronic; Royalties from Oxford University Press; LV: None;
HW: None; MSO: Consultant for National Parkinson Foundation; Grant
support from NIH, NPF, Michael J. Fox Foundation, Parkinson Alliance,
Smallwood Foundation, Bachmann-Strauss Foundation, Tourette Syndrome
Association, UP Foundation.
NR 79
TC 5
Z9 5
U1 2
U2 19
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 0020-7454
EI 1563-5279
J9 INT J NEUROSCI
JI Int. J. Neurosci.
PD JUL
PY 2015
VL 125
IS 7
BP 475
EP 485
DI 10.3109/00207454.2014.999268
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA CP4WV
UT WOS:000359884200001
PM 25526555
ER
PT J
AU Lee, S
Yamazaki, M
Harris, DR
Harper, GW
Ellen, J
AF Lee, Sonia
Yamazaki, Michiyo
Harris, D. Robert
Harper, Gary W.
Ellen, Jonathan
TI Social Support and Human Immunodeficiency Virus-Status Disclosure to
Friends and Family: Implications for Human Immunodeficiency
Virus-Positive Youth
SO JOURNAL OF ADOLESCENT HEALTH
LA English
DT Article
ID HIV-INFECTED ADOLESCENT; HIGH-RISK YOUTH; MEDICATION ADHERENCE;
MENTAL-HEALTH; URBAN YOUTH; STIGMA; WOMEN; PREDICTORS; PREVENTION;
MULTISITE
AB Purpose: The fear of negative reactions from friends and family members affects many human immunodeficiency virus (HIV)-positive adolescents' decisions regarding disclosure of their HIV status. The complex relationships and interplay among social support, fear of stigma, and disclosure of HIV status need to be better understood among youth living with HIV (YLHIV).
Methods: Social support from friends and family members and HIV status disclosure were examined among 402 youth, aged 12-24 years, living with HIV.
Results: In separate analyses, (1) HIV-positive youth who reported more than one close friend and (2) HIV-positive youth who reported that friends and family members continued to socialize with them after disclosure of their HIV diagnosis, had higher levels of perceived social support overall (both p<.05). Furthermore, perceived social support did not differ significantly between those participants for whom no family member knew their HIV status and those for whom at least one family member knew their status (p=.13). Race/ethnicity, sexual orientation, education level, and current living situation were not associated with family's knowledge of the participants' HIV infection status (p>.07).
Conclusion: This investigation adds important information concerning YLHIV, whose early disclosure experiences may influence their resilience and future coping mechanisms regarding experienced stigma, and thus influence the length of time they conceal their HIV status, their decision to disclose their status, and potentially their decisions regarding treatment. Interventions and support systems to assist YLHIV with disclosure, as well as medical care, may improve their overall quality of life. Published by Elsevier Inc. on behalf of Society for Adolescent Health and Medicine.
C1 [Lee, Sonia] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal & Pediat Infect Dis Branch, Bethesda, MD 20892 USA.
[Yamazaki, Michiyo] Johns Hopkins Univ, Dept Populat Family & Reprod Hlth, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Harris, D. Robert] Westat Corp, Rockville, MD USA.
[Harper, Gary W.] Univ Michigan, Dept Hlth Behav & Hlth Educ, Ann Arbor, MI 48109 USA.
[Ellen, Jonathan] Johns Hopkins Med, All Childrens Hosp, St Petersburg, FL USA.
RP Lee, S (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal & Pediat Infect Dis Branch, 6100 Execut Blvd,Room 4B11K, Bethesda, MD 20892 USA.
EM leesonia@mail.nih.gov
FU National Institutes of Health through the National Institute of Child
Health and Human Development [U01 HD040533]; National Institute on Drug
Abuse, National Institute of Mental Health; National Institute on
Alcohol Abuse and Alcoholism
FX This research is funded by grant U01 HD040533 from the National
Institutes of Health through the National Institute of Child Health and
Human Development, with supplemental funding from the National Institute
on Drug Abuse, National Institute of Mental Health, and National
Institute on Alcohol Abuse and Alcoholism.
NR 40
TC 1
Z9 1
U1 5
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1054-139X
EI 1879-1972
J9 J ADOLESCENT HEALTH
JI J. Adolesc. Health
PD JUL
PY 2015
VL 57
IS 1
BP 73
EP 80
DI 10.1016/j.jadohealth.2015.03.002
PG 8
WC Psychology, Developmental; Public, Environmental & Occupational Health;
Pediatrics
SC Psychology; Public, Environmental & Occupational Health; Pediatrics
GA CP7GT
UT WOS:000360055900009
PM 25940217
ER
PT J
AU Gilbert, AL
Knopf, AS
Fortenberry, JD
Hosek, SG
Kapogiannis, BG
Zimet, GD
AF Gilbert, Amy Lewis
Knopf, Amelia S.
Fortenberry, J. Dennis
Hosek, Sybil G.
Kapogiannis, Bill G.
Zimet, Gregory D.
TI Adolescent Self-Consent for Biomedical Human Immunodeficiency Virus
Prevention Research
SO JOURNAL OF ADOLESCENT HEALTH
LA English
DT Article
AB Purpose: The Adolescent Medicine Trials Network Protocol 113 (ATN113) is an open-label, multisite demonstration project and Phase II safety study of human immunodeficiency virus (HIV) preexposure prophylaxis with 15- to 17-year-old young men who have sex with men that requires adolescent consent for participation. The purpose of this study was to examine factors related to the process by which Institutional Review Boards (IRBs) and researchers made decisions regarding whether to approve and implement ATN113 so as to inform future biomedical HIV prevention research with high-risk adolescent populations.
Methods: Participants included 17 researchers at 13 sites in 12 states considering ATN113 implementation. Qualitative descriptive methods were used. Data sources included interviews and documents generated during the initiation process.
Results: A common process for initiating ATN113 emerged, and informants described how they identified and addressed practical, ethical, and legal challenges that arose. Informants described the process as responding to the protocol, preparing for IRB submission, abstaining from or proceeding with submission, responding to IRB concerns, and reacting to the outcomes. A complex array of factors impacting approval and implementation were identified, and ATN113 was ultimately implemented in seven of 13 sites. Informants also reflected on lessons learned that may help inform future biomedical HIV prevention research with high-risk adolescent populations.
Conclusions: The results illustrate factors for consideration in determining whether to implement such trials, demonstrate that such protocols have the potential to be approved, and highlight a need for clearer standards regarding biomedical HIV prevention research with high-risk adolescent populations. (C) 2015 Society for Adolescent Health and Medicine. All rights reserved.
C1 [Gilbert, Amy Lewis] Indiana Univ Sch Med, Dept Pediat, Childrens Hlth Serv Res, Indianapolis, IN 46202 USA.
[Gilbert, Amy Lewis] Regenstrief Inst Inc, Indianapolis, IN USA.
[Knopf, Amelia S.] Indiana Univ Sch Nursing, Indianapolis, IN USA.
[Fortenberry, J. Dennis; Zimet, Gregory D.] Indiana Univ Sch Med, Dept Pediat, Adolescent Med, Indianapolis, IN 46202 USA.
[Hosek, Sybil G.] John H Stroger Jr Hosp Cook Cty, Dept Psychiat, Chicago, IL USA.
[Kapogiannis, Bill G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Dept Hlth & Human Serv, NIH, Bethesda, MD USA.
RP Gilbert, AL (reprint author), Indiana Univ Sch Med, Dept Pediat, Childrens Hlth Serv Res, 410 West 10th St,Suite 1000, Indianapolis, IN 46202 USA.
EM amylewis@iu.edu
OI Gilbert, Amy/0000-0003-2492-178X; Zimet, Gregory/0000-0003-3835-937X
FU ATN; National Institutes of Health through the National Institute of
Child Health and Human Development [U01 HD 040533, U01 HD 040474];
National Institute on Drug Abuse; National Institute of Mental Health;
National Institute of Nursing Research [2T32 NR007066]
FX This substudy was supported by the ATN with funding from the National
Institutes of Health (U01 HD 040533 and U01 HD 040474) through the
National Institute of Child Health and Human Development (B.G.K. and S.
Lee) and with supplemental funding from the National Institute on Drug
Abuse (K. Davenny, R. Jenkins) and National Institute of Mental Health
(P. Brouwers and S. Allison). Additional support was provided by the
National Institute of Nursing Research (2T32 NR007066, A.S.K.).
NR 16
TC 3
Z9 3
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1054-139X
EI 1879-1972
J9 J ADOLESCENT HEALTH
JI J. Adolesc. Health
PD JUL
PY 2015
VL 57
IS 1
BP 113
EP 119
DI 10.1016/j.jadohealth.2015.03.017
PG 7
WC Psychology, Developmental; Public, Environmental & Occupational Health;
Pediatrics
SC Psychology; Public, Environmental & Occupational Health; Pediatrics
GA CP7GT
UT WOS:000360055900015
PM 26095412
ER
PT J
AU Kowalska, T
Ciesla, L
AF Kowalska, Teresa
Ciesla, Lukasz
TI Assessment of Antioxidant and Antibacterial Potential of Medicinal Herbs
and Botanical Preparations
SO JOURNAL OF AOAC INTERNATIONAL
LA English
DT Editorial Material
C1 [Kowalska, Teresa] Univ Silesia, Dept Gen Chem & Chromatog, Katowice, Poland.
[Ciesla, Lukasz] Med Univ Lublin, Dept Inorgan Chem, Lublin, Poland.
[Ciesla, Lukasz] NIA, Lab Clin Invest, Baltimore, MD 21224 USA.
RP Kowalska, T (reprint author), Univ Silesia, Dept Gen Chem & Chromatog, Katowice, Poland.
NR 0
TC 1
Z9 1
U1 1
U2 2
PU AOAC INT
PI GAITHERSBURG
PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA
SN 1060-3271
EI 1944-7922
J9 J AOAC INT
JI J. AOAC Int.
PD JUL-AUG
PY 2015
VL 98
IS 4
BP 847
EP 849
DI 10.5740/jaoacint.SGEIntro_Kowalska
PG 3
WC Chemistry, Analytical; Food Science & Technology
SC Chemistry; Food Science & Technology
GA CO9QD
UT WOS:000359509500001
PM 26268960
ER
PT J
AU Kim, S
Thiessen, PA
Bolton, EE
Bryant, SH
AF Kim, Sunghwan
Thiessen, Paul A.
Bolton, Evan E.
Bryant, Stephen H.
TI PUG-SOAP and PUG-REST: web services for programmatic access to chemical
information in PubChem
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID SMALL MOLECULES; SYSTEM; SMILES; ENTREZ
AB PubChem (http://pubchem.ncbi.nlm.nih.gov) is a public repository for information on chemical substances and their biological activities, developed and maintained by the US National Institutes of Health (NIH). PubChem contains more than 180 million depositor-provided chemical substance descriptions, 60 million unique chemical structures and 225 million bioactivity assay results, covering more than 9000 unique protein target sequences. As an information resource for the chemical biology research community, it routinely receives more than 1 million requests per day from an estimated more than 1 million unique users per month. Programmatic access to this vast amount of data is provided by several different systems, including the US National Center for Biotechnology Information (NCBI)'s Entrez Utilities (E-Utilities or E-Utils) and the PubChem Power User Gateway (PUG)-a common gateway interface (CGI) that exchanges data through eXtended Markup Language (XML). Further simplifying programmatic access, PubChem provides two additional general purpose web services: PUG-SOAP, which uses the simple object access protocol (SOAP) and PUG-REST, which is a Representational State Transfer (REST)-style interface. These interfaces can be harnessed in combination to access the data contained in PubChem, which is integrated with the more than thirty databases available within the NCBI Entrez system.
C1 [Kim, Sunghwan; Thiessen, Paul A.; Bolton, Evan E.; Bryant, Stephen H.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, US Dept HHS, Bethesda, MD 20894 USA.
RP Bolton, EE (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, US Dept HHS, Bethesda, MD 20894 USA.
EM bolton@ncbi.nlm.nih.gov
RI Kim, Sunghwan/A-6738-2008
OI Kim, Sunghwan/0000-0001-9828-2074
FU Intramural Research Program of the National Library of Medicine,
National Institutes of Health
FX Intramural Research Program of the National Library of Medicine,
National Institutes of Health (in part). Funding for open access charge:
Intramural Research Program of the National Library of Medicine,
National Institutes of Health.
NR 15
TC 7
Z9 7
U1 1
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JUL 1
PY 2015
VL 43
IS W1
BP W605
EP W611
DI 10.1093/nar/gkv396
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CP3IP
UT WOS:000359772700097
PM 25934803
ER
PT J
AU Matuszak, Z
Chignell, CF
Reszka, KJ
AF Matuszak, Zenon
Chignell, Collin F.
Reszka, Krzysztof J.
TI The acid-catalyzed interaction of melanin with nitrite ions. An EPR
investigation
SO NUKLEONIKA
LA English
DT Article
DE EPR; melanin; nitrite; nitrogen dioxide; nitrous acid; radicals
ID ELECTRON-SPIN-RESONANCE; OXIDE SYNTHASE ACTIVITY; MURINE MELANOMA;
RADICAL PRODUCTION; CHEMISTRY; KINETICS; PEROXYNITRITE; MECHANISM;
CELLS; PH
AB The interaction of synthetic dihydroxyphenylalanine (DOPA) melanin (DM) with nitrite ions, NO2-, in the pH 3.6-7.0 range, has been investigated using electron paramagnetic resonance (EPR). We found that especially at pH <5.5 (from ca. 5.5 to 3.6) the reaction of DM with nitrite generated large quantities of new melanin radicals, which implies the involvement of nitrous acid, HNO2, in the radical formation process. Measurements carried out at constant pH of 3.6 showed that the melanin signal increased together with nitrite concentration, reaching a plateau level which was more than fourfold larger compared to the initial signal amplitude observed in a nitrite-free buffer of the same pH. The effects of nitrite and DM concentrations on the melanin-free radical content were also investigated. It is proposed that the radicals are generated by one electron oxidation of melanin ortho-hydroquinone groups to ortho-semiquinones by HNO2 or related nitrogen oxides such as NO2 center dot radicals. The possible involvement of nitric oxide ((NO)-N-center dot) and peroxynitrite (ONOO-) in DM oxidation was also examined. In air-free solutions, nitric oxide per se did not generate melanin radicals; however, in the presence of oxygen a marked increase in the melanin EPR signal intensity was observed. This result is interpreted in terms of the generation of radicals via the oxidation of DM by peroxynitrite. Our findings suggest that melanin can function as a natural scavenger of nitrous acid and some nitrous acid-derived species. This property may be relevant to physiological functions of melanin pigments in vivo.
C1 [Matuszak, Zenon] AGH Univ Sci & Technol, Fac Phys & Appl Comp Sci, Dept Med Phys & Biophys, PL-30059 Krakow, Poland.
[Chignell, Collin F.; Reszka, Krzysztof J.] NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA.
RP Matuszak, Z (reprint author), AGH Univ Sci & Technol, Fac Phys & Appl Comp Sci, Dept Med Phys & Biophys, 30 Mickiewicza Ave, PL-30059 Krakow, Poland.
EM Zenon.Matuszak@fis.agh.edu.pl
NR 32
TC 0
Z9 0
U1 3
U2 4
PU INST NUCLEAR CHEMISTRY TECHNOLOGY
PI WARSAW
PA DORODNA 16 STR, 03-195 WARSAW, POLAND
SN 0029-5922
EI 1508-5791
J9 NUKLEONIKA
JI Nukleonika
PD JUL
PY 2015
VL 60
IS 3
BP 475
EP 481
DI 10.1515/nuka-2015-0084
PG 7
WC Chemistry, Inorganic & Nuclear; Physics, Nuclear
SC Chemistry; Physics
GA CP5WG
UT WOS:000359955200019
ER
PT J
AU Bewley, C
AF Bewley, C.
TI Beyond structure Diverse mechanisms of anti-infective natural products
SO PLANTA MEDICA
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Pharmacognosy
CY JUL 25-29, 2015
CL CO
SP Amer Soc Pharmacognosy
C1 [Bewley, C.] NIDDK, Nat Prod Chem Sect, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0032-0943
EI 1439-0221
J9 PLANTA MED
JI Planta Med.
PD JUL
PY 2015
VL 81
IS 11
MA SL5
BP 857
EP 857
PG 1
WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary
Medicine; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary
Medicine
GA CP6AP
UT WOS:000359967000010
ER
PT J
AU Gustafson, KR
AF Gustafson, K. R.
TI Mining the extensive chemical diversity of the NCl natural products
repository for new agents that can target HIV
SO PLANTA MEDICA
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Pharmacognosy
CY JUL 25-29, 2015
CL CO
SP Amer Soc Pharmacognosy
C1 [Gustafson, K. R.] NCI, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21702 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0032-0943
EI 1439-0221
J9 PLANTA MED
JI Planta Med.
PD JUL
PY 2015
VL 81
IS 11
MA IL1
BP 858
EP 858
PG 1
WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary
Medicine; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary
Medicine
GA CP6AP
UT WOS:000359967000016
ER
PT J
AU Risinger, AL
Du, L
Robles, A
Sarkar, P
Perez, A
King, JB
Dybdal-Hargreaves, N
Dai, W
O'Keefe, B
Cichewicz, RH
Mooberly, SL
AF Risinger, A. L.
Du, L.
Robles, A.
Sarkar, P.
Perez, A.
King, J. B.
Dybdal-Hargreaves, N.
Dai, W.
O'Keefe, B.
Cichewicz, R. H.
Mooberly, S. L.
TI Utilizing differential cytotoxicity screening to identify lead compounds
for rare adult and pediatric tumors
SO PLANTA MEDICA
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Pharmacognosy
CY JUL 25-29, 2015
CL CO
SP Amer Soc Pharmacognosy
C1 [Risinger, A. L.; Robles, A.; Sarkar, P.; Perez, A.; Dybdal-Hargreaves, N.; Mooberly, S. L.] UT Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78229 USA.
[Risinger, A. L.; Mooberly, S. L.] UT Hlth Sci Ctr, Dept Canc Therapy, San Antonio, TX 78229 USA.
[Risinger, A. L.; Mooberly, S. L.] UT Hlth Sci Ctr, Res Ctr, San Antonio, TX 78229 USA.
[Du, L.; King, J. B.; Dai, W.; Cichewicz, R. H.] Univ Oklahoma, Nat Prod Discovery Grp, Norman, OK 73019 USA.
[Du, L.; King, J. B.; Dai, W.; Cichewicz, R. H.] Univ Oklahoma, Dept Chem & Biochem, Norman, OK 73019 USA.
[O'Keefe, B.] NCI, Nat Prod Branch, Frederick, MD 21702 USA.
[O'Keefe, B.] NCI, Mol Targets Lab, Frederick, MD 21702 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0032-0943
EI 1439-0221
J9 PLANTA MED
JI Planta Med.
PD JUL
PY 2015
VL 81
IS 11
MA IL39
BP 866
EP 866
PG 1
WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary
Medicine; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary
Medicine
GA CP6AP
UT WOS:000359967000053
ER
PT J
AU Chan, STS
Patel, PR
Martin, GE
Williamson, RT
Sauri, J
Buevich, AV
Ransom, TR
Henrich, CJ
McKee, TC
Figg, WD
McMahon, JB
Schnermann, MJ
Gustafson, KR
AF Chan, S. T. S.
Patel, P. R.
Martin, G. E.
Williamson, R. T.
Sauri, J.
Buevich, A., V
Ransom, T. R.
Henrich, C. J.
McKee, T. C.
Figg, W. D.
McMahon, J. B.
Schnermann, M. J.
Gustafson, K. R.
TI Isolation and identification of novel natural products that inhibit
P300/HIF-1 alpha interaction
SO PLANTA MEDICA
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Pharmacognosy
CY JUL 25-29, 2015
CL CO
SP Amer Soc Pharmacognosy
C1 [Chan, S. T. S.; Ransom, T. R.; Henrich, C. J.; McKee, T. C.; McMahon, J. B.; Gustafson, K. R.] NCI, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21702 USA.
[Patel, P. R.; Schnermann, M. J.] NCI, Chem Biol Lab, Ctr Canc Res, Frederick, MD 21702 USA.
[Patel, P. R.] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
[Martin, G. E.; Williamson, R. T.; Sauri, J.; Buevich, A., V] Merck & Co Inc, NMR Struct Elucidat Proc & Analyt Chem, Rahway, NJ 07065 USA.
[Henrich, C. J.] Leidos Biomed Res Inc, Basic Sci Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Figg, W. D.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RI Figg Sr, William/M-2411-2016
NR 0
TC 0
Z9 0
U1 0
U2 1
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0032-0943
EI 1439-0221
J9 PLANTA MED
JI Planta Med.
PD JUL
PY 2015
VL 81
IS 11
MA CL10
BP 873
EP 873
PG 1
WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary
Medicine; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary
Medicine
GA CP6AP
UT WOS:000359967000089
ER
PT J
AU Beutler, JA
AF Beutler, J. A.
TI Development of englerins as cancer therapeutics
SO PLANTA MEDICA
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Pharmacognosy
CY JUL 25-29, 2015
CL CO
SP Amer Soc Pharmacognosy
C1 [Beutler, J. A.] NCI, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21702 USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0032-0943
EI 1439-0221
J9 PLANTA MED
JI Planta Med.
PD JUL
PY 2015
VL 81
IS 11
MA CL19
BP 875
EP 875
PG 1
WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary
Medicine; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary
Medicine
GA CP6AP
UT WOS:000359967000098
ER
PT J
AU Andrews, KW
Dang, PT
Savarala, S
Gusev, PA
Han, F
Pehrsson, PR
Harnly, JM
Chen, P
Dwyer, JT
Betz, JM
Saldanha, LG
Costello, RB
AF Andrews, K. W.
Dang, P. T.
Savarala, S.
Gusev, P. A.
Han, F.
Pehrsson, P. R.
Harnly, J. M.
Chen, P.
Dwyer, J. T.
Betz, J. M.
Saldanha, L. G.
Costello, R. B.
TI Botanical initiative for the dietary supplement ingredient database
(DSID): Preliminary data for green tea suppliments
SO PLANTA MEDICA
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Pharmacognosy
CY JUL 25-29, 2015
CL CO
SP Amer Soc Pharmacognosy
C1 [Andrews, K. W.; Dang, P. T.; Savarala, S.; Gusev, P. A.; Han, F.; Pehrsson, P. R.] USDA, Nutrient Data Lab, Beltsville, MD 20705 USA.
[Harnly, J. M.; Chen, P.] USDA, Food Composit & Methods Dev Lab, Beltsville, MD 20705 USA.
[Dwyer, J. T.; Betz, J. M.; Saldanha, L. G.; Costello, R. B.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0032-0943
EI 1439-0221
J9 PLANTA MED
JI Planta Med.
PD JUL
PY 2015
VL 81
IS 11
MA PG6
BP 887
EP 887
PG 1
WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary
Medicine; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary
Medicine
GA CP6AP
UT WOS:000359967000153
ER
PT J
AU Grkovic, T
Akee, R
Evans, J
Collins, JM
O'Keefe, B
AF Grkovic, T.
Akee, R.
Evans, J.
Collins, J. M.
O'Keefe, B.
TI Biologically active natural products from Cassine viburnifolia
SO PLANTA MEDICA
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Pharmacognosy
CY JUL 25-29, 2015
CL CO
SP Amer Soc Pharmacognosy
C1 [Grkovic, T.; Akee, R.; Evans, J.] Frederick Natl Lab Canc Res, Nat Prod Support Grp, Leidos Biomed Res Inc, Frederick, MD 21702 USA.
[Evans, J.] NCI, Data Management Serv Inc, Frederick, MD 21702 USA.
[Collins, J. M.; O'Keefe, B.] Frederick Natl Lab Canc Res, Nat Prod Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA.
[O'Keefe, B.] Frederick Natl Lab Canc Res, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21702 USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0032-0943
EI 1439-0221
J9 PLANTA MED
JI Planta Med.
PD JUL
PY 2015
VL 81
IS 11
MA PH9
BP 891
EP 891
PG 1
WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary
Medicine; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary
Medicine
GA CP6AP
UT WOS:000359967000175
ER
PT J
AU Thornburg, CC
Grkovic, T
Britt, JR
Akee, RK
Whitt, JA
Evans, JR
Grothaus, PG
Collins, JM
O'Keefe, BR
AF Thornburg, C. C.
Grkovic, T.
Britt, J. R.
Akee, R. K.
Whitt, J. A.
Evans, J. R.
Grothaus, P. G.
Collins, J. M.
O'Keefe, B. R.
TI Development of a natural product-based fraction library for improved
performance in high-throughput screening systems
SO PLANTA MEDICA
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Pharmacognosy
CY JUL 25-29, 2015
CL CO
SP Amer Soc Pharmacognosy
C1 [Thornburg, C. C.; Grkovic, T.; Britt, J. R.; Akee, R. K.; Whitt, J. A.] Leidos Biomed Res Inc, Nat Prod Support Grp, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Evans, J. R.] NCI, Nat Prod Support Grp, Data Management Serv Inc, Frederick, MD 21702 USA.
[Grothaus, P. G.; Collins, J. M.; O'Keefe, B. R.] NCI, Nat Prod Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA.
[O'Keefe, B. R.] NCI, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21702 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0032-0943
EI 1439-0221
J9 PLANTA MED
JI Planta Med.
PD JUL
PY 2015
VL 81
IS 11
MA PK21
BP 900
EP 900
PG 1
WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary
Medicine; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary
Medicine
GA CP6AP
UT WOS:000359967000215
ER
PT J
AU Colegate, SM
Boppre, M
Monzon, J
Betz, JM
AF Colegate, S. M.
Boppre, M.
Monzon, J.
Betz, J. M.
TI 1,2-dehydropyrrolizidine alkaloids in the traditional Andean herbal
medicine "Asmachilca"
SO PLANTA MEDICA
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Pharmacognosy
CY JUL 25-29, 2015
CL CO
SP Amer Soc Pharmacognosy
C1 [Colegate, S. M.] ARS, USDA, Poisonous Plant Res Lab, Logan, UT 84341 USA.
[Colegate, S. M.] Utah State Univ, Dept Anim Dairy & Vet Sci, Logan, UT 84322 USA.
[Boppre, M.; Monzon, J.] Univ Freiburg, Forstzool & Entomol, D-79085 Freiburg, Germany.
[Betz, J. M.] NIH, ODS, Bethesda, MD 20892 USA.
RI Boppre, Michael/P-4346-2016
NR 0
TC 0
Z9 0
U1 0
U2 0
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0032-0943
EI 1439-0221
J9 PLANTA MED
JI Planta Med.
PD JUL
PY 2015
VL 81
IS 11
MA PM7
BP 905
EP 905
PG 1
WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary
Medicine; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary
Medicine
GA CP6AP
UT WOS:000359967000236
ER
PT J
AU Chan, STS
Patel, PR
Martin, GE
Williamson, RT
Sauri, J
Buevich, AV
Ransom, TR
Henrich, CJ
McKee, TC
Figg, WD
McMahon, JB
Schnermann, MJ
Gustafson, KR
AF Chan, S. T. S.
Patel, P. R.
Martin, G. E.
Williamson, R. T.
Sauri, J.
Buevich, A., V
Ransom, T. R.
Henrich, C. J.
McKee, T. C.
Figg, W. D.
McMahon, J. B.
Schnermann, M. J.
Gustafson, K. R.
TI Isolation and identification of novel natural products that inhibit
P300/HIF-1 alpha interaction
SO PLANTA MEDICA
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Pharmacognosy
CY JUL 25-29, 2015
CL CO
SP Amer Soc Pharmacognosy
C1 [Chan, S. T. S.; Ransom, T. R.; Henrich, C. J.; McKee, T. C.; McMahon, J. B.; Gustafson, K. R.] NCI, Mol Targets Lab, Ctr Canc Res, Ft Detrick, MD 21702 USA.
[Patel, P. R.; Schnermann, M. J.] NCI, Biol Chem Lab, Ctr Canc Res, Ft Detrick, MD 21702 USA.
[Patel, P. R.] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
[Martin, G. E.; Williamson, R. T.; Sauri, J.; Buevich, A., V] Merck & Co Inc, NMR Struct Elucidat Proc & Analyt Chem, Rahway, NJ 07065 USA.
[Henrich, C. J.] Leidos Biomed Res Inc, Basic Sci Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Figg, W. D.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
OI Sauri, Josep/0000-0002-2706-2426
NR 0
TC 0
Z9 0
U1 0
U2 0
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0032-0943
EI 1439-0221
J9 PLANTA MED
JI Planta Med.
PD JUL
PY 2015
VL 81
IS 11
MA PQ7
BP 909
EP 909
PG 1
WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary
Medicine; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary
Medicine
GA CP6AP
UT WOS:000359967000258
ER
PT J
AU Sauri, J
Chan, STS
Buevich, AV
Gustafson, KR
Williamson, RT
Martin, GE
AF Sauri, J.
Chan, S. T. S.
Buevich, A., V
Gustafson, K. R.
Williamson, R. T.
Martin, G. E.
TI Structure elucidation of a proton-deficient natural product using
LR-HSQMBC supported by DFT calculations
SO PLANTA MEDICA
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Pharmacognosy
CY JUL 25-29, 2015
CL CO
SP Amer Soc Pharmacognosy
C1 [Sauri, J.; Buevich, A., V; Williamson, R. T.; Martin, G. E.] Merck & Co Inc, NMR Struct Elucidat Proc & Analyt Chem, Rahway, NJ 07065 USA.
[Chan, S. T. S.; Gustafson, K. R.] NCI, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21701 USA.
OI Sauri, Josep/0000-0002-2706-2426
NR 0
TC 0
Z9 0
U1 0
U2 1
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0032-0943
EI 1439-0221
J9 PLANTA MED
JI Planta Med.
PD JUL
PY 2015
VL 81
IS 11
MA PQ32
BP 914
EP 914
PG 1
WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary
Medicine; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary
Medicine
GA CP6AP
UT WOS:000359967000281
ER
PT J
AU Forcina, G
Castro, A
Bokesch, HR
Kucera, K
McMahon, JB
Gustafson, KR
Strobel, S
AF Forcina, G.
Castro, A.
Bokesch, H. R.
Kucera, K.
McMahon, J. B.
Gustafson, K. R.
Strobel, S.
TI Stelliosphaerols A and B, sesquiterpene-polyol conjugates from an
Ecuadorian fungal endophyte
SO PLANTA MEDICA
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Pharmacognosy
CY JUL 25-29, 2015
CL CO
SP Amer Soc Pharmacognosy
C1 [Forcina, G.; Kucera, K.] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA.
[Castro, A.; Bokesch, H. R.; McMahon, J. B.; Gustafson, K. R.] NCI, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21702 USA.
[Bokesch, H. R.; Strobel, S.] Leidos Biomed Res Inc, Frederick Natl Lab, Basic Sci Program, Frederick, MD 21702 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0032-0943
EI 1439-0221
J9 PLANTA MED
JI Planta Med.
PD JUL
PY 2015
VL 81
IS 11
MA PT11
BP 919
EP 919
PG 1
WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary
Medicine; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary
Medicine
GA CP6AP
UT WOS:000359967000304
ER
PT J
AU Espindola, LS
Wilson, B
Beutler, JA
Gustafson, KR
O'Keefe, BR
AF Espindola, L. S.
Wilson, B.
Beutler, J. A.
Gustafson, K. R.
O'Keefe, B. R.
TI Brazilian cerrado biome plant extract bank screening in inflammatory
disease and cancer enzymes
SO PLANTA MEDICA
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Pharmacognosy
CY JUL 25-29, 2015
CL CO
SP Amer Soc Pharmacognosy
C1 [Espindola, L. S.] Univ Brasilia, Lab Farmacognosia, Brasilia, DF, Brazil.
[Espindola, L. S.; Wilson, B.; Beutler, J. A.; Gustafson, K. R.; O'Keefe, B. R.] NCI, Mol Targets Lab, NIH, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0032-0943
EI 1439-0221
J9 PLANTA MED
JI Planta Med.
PD JUL
PY 2015
VL 81
IS 11
MA PX77
BP 946
EP 946
PG 1
WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary
Medicine; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary
Medicine
GA CP6AP
UT WOS:000359967000435
ER
PT J
AU McKee, TC
AF McKee, T. C.
TI Funding opportunities in the NCI'S cancer diagnosis program
SO PLANTA MEDICA
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Pharmacognosy
CY JUL 25-29, 2015
CL CO
SP Amer Soc Pharmacognosy
C1 [McKee, T. C.] NCI, Diagnost Biomarkers & Technol Branch, Canc Diag Program, DCTD, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0032-0943
EI 1439-0221
J9 PLANTA MED
JI Planta Med.
PD JUL
PY 2015
VL 81
IS 11
MA PZB2
BP 952
EP 952
PG 1
WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary
Medicine; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary
Medicine
GA CP6AP
UT WOS:000359967000465
ER
PT J
AU Nemeth, K
Wilson, TM
Ren, JQJ
Sabatino, M
Stroncek, DM
Krepuska, M
Bai, Y
Robey, PG
Metcalfe, DD
Mezey, E
AF Nemeth, Krisztian
Wilson, Todd M.
Ren, Jiaqiang J.
Sabatino, Marianna
Stroncek, David M.
Krepuska, Miklos
Bai, Yun
Robey, Pamela G.
Metcalfe, Dean D.
Mezey, Eva
TI Impaired function of bone marrow stromal cells in systemic mastocytosis
SO STEM CELL RESEARCH
LA English
DT Article
ID STEM-CELLS; DISEASE; MUTATIONS
AB Patients with systemic mastocytosis (SM) have a wide variety of problems, including skeletal abnormalities. The disease results from a mutation of the stem cell receptor (c-kit) in mast cells and we wondered if the function of bone marrow stromal cells (BMSCs; also known as MSCs or mesenchymal stem cells) might be affected by the invasion of bone marrow by mutant mast cells. As expected, BMSCs from SM patients do not have a mutation in c-kit, but they proliferate poorly. In addition, while osteogenic differentiation of the BMSCs seems to be deficient, their adipogenic potential appears to be increased. Since the hematopoietic supportive abilities of BMSCs are also important, we also studied the engraftment in NSG mice of human CD34(+) hematopoietic progenitors, after being co-cultured with BMSCs of healthy volunteers vs. BMSCs derived from patients with SM. BMSCs derived from the bone marrow of patients with SM could not support hematopoiesis to the extent that healthy BMSCs do. Finally, we performed an expression analysis and found significant differences between healthy and SM derived BMSCs in the expression of genes with a variety of functions, including the WNT signaling, ossification, and bone remodeling. We suggest that some of the symptoms associated with SM might be driven by epigenetic changes in BMSCs caused by dysfunctional mast cells in the bone marrow of the patients. Published by Elsevier B.V.
C1 [Nemeth, Krisztian; Krepuska, Miklos; Robey, Pamela G.; Mezey, Eva] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA.
[Wilson, Todd M.; Bai, Yun; Metcalfe, Dean D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
[Ren, Jiaqiang J.; Sabatino, Marianna; Stroncek, David M.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Nemeth, K (reprint author), Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM nemethk@mail.nih.gov; mezeye@mail.nih.gov
RI Robey, Pamela/H-1429-2011
OI Robey, Pamela/0000-0002-5316-5576
FU DIR; NIAID of the IRP; NIAID of the NIH; NIAID of the DHHS; NIDCR
FX This work was supported by the DIR, NIDCR and NIAID of the IRP, NIH,
DHHS. We thank the patients, healthy volunteers and clinical research
staff for their contributions.
NR 28
TC 3
Z9 3
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1873-5061
EI 1876-7753
J9 STEM CELL RES
JI Stem Cell Res.
PD JUL
PY 2015
VL 15
IS 1
BP 42
EP 53
DI 10.1016/j.scr.2015.04.005
PG 12
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology
SC Cell Biology; Biotechnology & Applied Microbiology
GA CP6JZ
UT WOS:000359994400005
PM 26001169
ER
PT J
AU Sworder, BJ
Yoshizawa, S
Mishra, PJ
Cherman, N
Kuznetsov, SA
Merlino, G
Balakumaran, A
Robey, PG
AF Sworder, Brian J.
Yoshizawa, Sayuri
Mishra, Prasun J.
Cherman, Natasha
Kuznetsov, Sergei A.
Merlino, Glenn
Balakumaran, Arun
Robey, Pamela G.
TI Molecular profile of clonal strains of human skeletal stem/progenitor
cells with different potencies (vol 14, pg 297, 2015)
SO STEM CELL RESEARCH
LA English
DT Correction
C1 [Sworder, Brian J.; Yoshizawa, Sayuri; Cherman, Natasha; Kuznetsov, Sergei A.; Balakumaran, Arun; Robey, Pamela G.] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Sworder, Brian J.] Boston Univ, Sch Med, Grad Program Mol Med, Boston, MA 02215 USA.
[Mishra, Prasun J.; Merlino, Glenn] NCI, Lab Canc Biol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Robey, PG (reprint author), Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
EM probey@dir.nidcr.nih.gov
RI Robey, Pamela/H-1429-2011
OI Robey, Pamela/0000-0002-5316-5576
NR 1
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1873-5061
EI 1876-7753
J9 STEM CELL RES
JI Stem Cell Res.
PD JUL
PY 2015
VL 15
IS 1
BP 269
EP 269
DI 10.1016/j.scr.2015.05.008
PG 1
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology
SC Cell Biology; Biotechnology & Applied Microbiology
GA CP6JZ
UT WOS:000359994400028
ER
PT J
AU Jabbi, M
Kohn, PD
Nash, T
Ianni, A
Coutlee, C
Holroyd, T
Carver, FW
Chen, Q
Cropp, B
Kippenhan, JS
Robinson, SE
Coppola, R
Berman, KF
AF Jabbi, Mbemba
Kohn, Philip D.
Nash, Tiffany
Ianni, Angela
Coutlee, Christopher
Holroyd, Tom
Carver, Frederick W.
Chen, Qiang
Cropp, Brett
Kippenhan, J. Shane
Robinson, Stephen E.
Coppola, Richard
Berman, Karen F.
TI Convergent BOLD and Beta-Band Activity in Superior Temporal Sulcus and
Frontolimbic Circuitry Underpins Human Emotion Cognition
SO CEREBRAL CORTEX
LA English
DT Article
DE coupling; emotion; neural; STS; transient
ID HUMAN BRAIN; NEURONAL OSCILLATIONS; FACIAL EXPRESSIONS; CORTICAL
NETWORKS; SOCIAL COGNITION; FACE PERCEPTION; MEG; SYNCHRONIZATION;
SYSTEM; RECOGNITION
AB The processing of social information in the human brain is widely distributed neuroanatomically and finely orchestrated over time. However, a detailed account of the spatiotemporal organization of these key neural underpinnings of human social cognition remains to be elucidated. Here, we applied functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) in the same participants to investigate spatial and temporal neural patterns evoked by viewing videos of facial muscle configurations. We show that observing the emergence of expressions elicits sustained blood oxygenation level-dependent responses in the superior temporal sulcus (STS), a region implicated in processing meaningful biological motion. We also found corresponding event-related changes in sustained MEG betaband (14-30 Hz) oscillatory activity in the STS, consistent with the possible role of beta-band activity in visual perception. Dynamically evolving fearful and happy expressions elicited early (0-400 ms) transient beta-band activity in sensorimotor cortex that persisted beyond 400 ms, at which time it became accompanied by a frontolimbic spread (400-1000 ms). In addition, individual differences in sustained STS beta-band activity correlated with speed of emotion recognition, substantiating the behavioral relevance of these signals. This STS beta-band activity showed valence-specific coupling with the time courses of facial movements as they emerged into full-blown fearful and happy expressions (negative and positive coupling, respectively). These data offer new insights into the perceptual relevance and orchestrated function of the STS and interconnected pathways in social-emotion cognition.
C1 [Jabbi, Mbemba; Kohn, Philip D.; Nash, Tiffany; Ianni, Angela; Coutlee, Christopher; Cropp, Brett; Kippenhan, J. Shane; Berman, Karen F.] NIMH, Sect Integrat Neuroimaging, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Jabbi, Mbemba; Kohn, Philip D.; Nash, Tiffany; Ianni, Angela; Coutlee, Christopher; Chen, Qiang; Cropp, Brett; Kippenhan, J. Shane; Coppola, Richard; Berman, Karen F.] NIMH, Clin Brain Disorders Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Holroyd, Tom; Carver, Frederick W.; Robinson, Stephen E.; Coppola, Richard] NIMH, MEG Core Facil, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Jabbi, M (reprint author), NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM jabbim@gmail.com
FU National Institute of Mental Health at the National Institutes of Health
FX This work was funded by the Intramural Research Program of the National
Institute of Mental Health at the National Institutes of Health.
ClinicalTrials.gov Identifier number: NCT00004571; Protocol ID number:
00-M-0085.
NR 54
TC 5
Z9 5
U1 3
U2 8
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1047-3211
EI 1460-2199
J9 CEREB CORTEX
JI Cereb. Cortex
PD JUL
PY 2015
VL 25
IS 7
BP 1878
EP 1888
DI 10.1093/cercor/bht427
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA CO7DS
UT WOS:000359319700018
PM 24464944
ER
PT J
AU Matyas, RA
Mumford, SL
Schliep, KC
Ahrens, KA
Sjaarda, LA
Perkins, NJ
Filiberto, AC
Mattison, D
Zarek, SM
Wactawski-Wende, J
Schisterman, EF
AF Matyas, R. A.
Mumford, S. L.
Schliep, K. C.
Ahrens, K. A.
Sjaarda, L. A.
Perkins, N. J.
Filiberto, A. C.
Mattison, D.
Zarek, S. M.
Wactawski-Wende, J.
Schisterman, E. F.
TI Effects of over-the-counter analgesic use on reproductive hormones and
ovulation in healthy, premenopausal women
SO HUMAN REPRODUCTION
LA English
DT Article
DE over-the-counter drugs; analgesics; ovulation; reproductive hormones
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; LOW-DOSE ASPIRIN; MENSTRUAL-CYCLE;
PREGNANCY; POPULATION; STRESS; TRIAL; ASSOCIATION; THROMBOXANE; PATTERNS
AB STUDY QUESTION: Does use of commonly used over-the-counter (OTC) pain medication affect reproductive hormones and ovulatory function in premenopausal women?
SUMMARY ANSWER: Few associations were found between analgesic medication use and reproductive hormones, but use during the follicular phase was associated with decreased odds of sporadic anovulation after adjusting for potential confounders.
WHAT IS KNOWN ALREADY: Analgesic medications are the most commonly used OTC drugs among women, but their potential effects on reproductive function are unclear.
STUDY DESIGN, SIZE, DURATION: The BioCycle Study was a prospective, observational cohort study (2005-2007) which followed 259 women for one (n = 9) or two (n = 250) menstrual cycles.
PARTICIPANTS, SETTING, METHODS: Two hundred and fifty-nine healthy, premenopausal women not using hormonal contraception and living in western New York state. Study visits took place at the University at Buffalo.
MAIN RESULTS AND THE ROLE OF CHANCE: During study participation, 68% (n = 175) of women indicated OTC analgesic use. Among users, 45% used ibuprofen, 33% acetaminophen, 10% aspirin and 10% naproxen. Analgesic use during the follicular phase was associated with decreased odds of sporadic anovulation after adjusting for age, race, body mass index, perceived stress level and alcohol consumption (OR 0.36 [0.17, 0.75]). Results remained unchanged after controlling for potential confounding by indication by adjusting for 'healthy' cycle indicators such as amount of blood loss and menstrual pain during the preceding menstruation. Moreover, luteal progesterone was higher (% difference = 14.0, 21.6-32.1, P = 0.08 adjusted) in cycles with follicular phase analgesic use, but no associations were observed with estradiol, LH or FSH.
LIMITATIONS, REASONS FOR CAUTION: Self-report daily diaries are not validated measures of medication usage, which could lead to some classification error of medication use. We were also limited in our evaluation of aspirin and naproxen which were used by few women.
WIDER IMPLICATIONS OF THE FINDINGS: The observed associations between follicular phase analgesic use and higher progesterone and a lower probability of sporadic anovulation indicate that OTC pain medication use is likely not harmful to reproduction function, and certain medications possibly improve ovulatory function.
STUDY FUNDING/COMPETING INTERESTS: This work 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 # HHSN275200403394C). The authors have no conflicts of interest to disclose.
C1 [Matyas, R. A.; Mumford, S. L.; Schliep, K. C.; Ahrens, K. A.; Sjaarda, L. A.; Perkins, N. J.; Filiberto, A. C.; Zarek, S. M.; Schisterman, E. F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, Rockville, MD 20852 USA.
[Mattison, D.] Risk Sci Int, Ottawa, ON, Canada.
[Mattison, D.] Univ Ottawa, Ottawa, ON, Canada.
[Zarek, S. M.] NICHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Wactawski-Wende, J.] SUNY Buffalo, Dept Epidemiol & Environm Hlth, Buffalo, NY 14260 USA.
RP Schisterman, EF (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, 6100 Execut Blvd,7B03, Rockville, MD 20852 USA.
EM schistee@mail.nih.gov
OI Perkins, Neil/0000-0002-6802-4733; Sjaarda, Lindsey/0000-0003-0539-8110;
Schisterman, Enrique/0000-0003-3757-641X
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health [HHSN275200403394C]
FX This work 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 #
HHSN275200403394C).
NR 32
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U1 1
U2 10
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0268-1161
EI 1460-2350
J9 HUM REPROD
JI Hum. Reprod.
PD JUL
PY 2015
VL 30
IS 7
BP 1714
EP 1723
DI 10.1093/humrep/dev099
PG 10
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA CP2XS
UT WOS:000359741800023
PM 25954035
ER
PT J
AU Tchounwou, PB
AF Tchounwou, Paul B.
TI Eleventh International Symposium on Recent Advances in Environmental
Health Research
SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
LA English
DT Editorial Material
C1 Jackson State Univ, Coll Sci Engn & Technol, NIH, RCMI Ctr Environm Hlth, Jackson, MS 39217 USA.
RP Tchounwou, PB (reprint author), Jackson State Univ, Coll Sci Engn & Technol, NIH, RCMI Ctr Environm Hlth, 1400 Lynch St,Box 18750, Jackson, MS 39217 USA.
EM paul.b.tchounwou@jsums.edu
NR 4
TC 1
Z9 1
U1 0
U2 0
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1660-4601
J9 INT J ENV RES PUB HE
JI Int. J. Environ. Res. Public Health
PD JUL
PY 2015
VL 12
IS 7
BP 7635
EP 7637
DI 10.3390/ijerph120707635
PG 3
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health
GA CO7MB
UT WOS:000359342300036
ER
PT J
AU Qin, M
Huang, TJ
Kader, M
Krych, L
Xia, ZY
Burlin, T
Zeidler, Z
Zhao, TR
Smith, CB
AF Qin, Mei
Huang, Tianjian
Kader, Michael
Krych, Leland
Xia, Zengyan
Burlin, Thomas
Zeidler, Zachary
Zhao, Tingrui
Smith, Carolyn B.
TI R-Baclofen Reverses a Social Behavior Deficit and Elevated Protein
Synthesis in a Mouse Model of Fragile X Syndrome
SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE Fragile X syndrome; mTOR; protein synthesis; R-baclofen; social behavior
ID MENTAL-RETARDATION; HIPPOCAMPAL-NEURONS; INCREASED RATES; IN-VIVO; FMR1;
MICE; RECEPTOR; INHIBITION; PLASTICITY; GLUCOSE
AB Background: Fragile X syndrome (FXS) is the most common known inherited form of intellectual disability and the single genomic cause of autism spectrum disorders. It is caused by the absence of a fragile X mental retardation gene (Fmr1) product, FMRP, an RNA-binding translation suppressor. Elevated rates of protein synthesis in the brain and an imbalance between synaptic signaling via glutamate and gamma-aminobutyric acid (GABA) are both considered important in the pathogenesis of FXS. In a mouse model of FXS (Fmr1 knockout [KO]), treatment with R-baclofen reversed some behavioral and biochemical phenotypes. A remaining crucial question is whether R-baclofen is also able to reverse increased brain protein synthesis rates.
Methods: To answer this question, we measured regional rates of cerebral protein synthesis in vivo with the L-[1-C-14]leucine method in vehicle- and R-baclofen-treated wildtype and Fmr1 KO mice. We further probed signaling pathways involved in the regulation of protein synthesis.
Results: Acute R-baclofen administration corrected elevated protein synthesis and reduced deficits on a test of social behavior in adult Fmr1 KO mice. It also suppressed activity of the mammalian target of rapamycin pathway, particularly in synaptosome-enriched fractions, but it had no effect on extracellular-regulated kinase 1/2 activity. Ninety min after R-baclofen treatment, we observed an increase in metabotropic glutamate receptor 5 expression in the frontal cortex, a finding that may shed light on the tolerance observed in human studies with this drug.
Conclusions: Our results suggest that treatment via activation of the GABA (GABA receptor subtype B) system warrants further study in patients with FXS.
C1 [Qin, Mei; Huang, Tianjian; Kader, Michael; Krych, Leland; Xia, Zengyan; Burlin, Thomas; Zeidler, Zachary; Zhao, Tingrui; Smith, Carolyn B.] NIMH, Sect Neuroadaptat & Prot Metab, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Smith, CB (reprint author), NIMH, Sect Neuroadaptat & Prot Metab, NIH, 10 Ctr Dr,Rm 2D54, Bethesda, MD 20892 USA.
EM beebe@mail.nih.gov
OI Zeidler, Zachary/0000-0001-6539-4360
FU Intramural Research Program of the National Institute of Mental Health,
National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute of Mental Health, National Institutes of Health.
NR 31
TC 3
Z9 3
U1 2
U2 12
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1461-1457
EI 1469-5111
J9 INT J NEUROPSYCHOPH
JI Int. J. Neuropsychopharmacol.
PD JUL
PY 2015
VL 18
IS 9
DI 10.1093/ijnp/pyv034
PG 13
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA CP2JT
UT WOS:000359704000006
ER
PT J
AU Uno, Y
Kojima, H
Omori, T
Corvi, R
Honma, M
Schechtman, LM
Tice, RR
Burlinson, B
Escobar, PA
Kraynak, AR
Nakagawa, Y
Nakajima, M
Pant, K
Asano, N
Lovell, D
Morita, T
Ohnob, Y
Hayashi, M
AF Uno, Yoshifumi
Kojima, Hajime
Omori, Takashi
Corvi, Raffaella
Honma, Masamistu
Schechtman, Leonard M.
Tice, Raymond R.
Burlinson, Brian
Escobar, Patricia A.
Kraynak, Andrew R.
Nakagawa, Yuzuki
Nakajima, Madoka
Pant, Kamala
Asano, Norihide
Lovell, David
Morita, Takeshi
Ohnob, Yasuo
Hayashi, Makoto
TI JaCVAM-organized international validation study of the in vivo rodent
alkaline comet assay for the detection of genotoxic carcinogens: I.
Summary of pre-validation study results
SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS
LA English
DT Article
DE Comet assay; Validation study; In vivo; Rodent; Genotoxicity; JaCVAM
ID DNA-DAMAGE; ADDUCT FORMATION; ACRYLAMIDE; RATS; RECOMMENDATIONS;
RADIATION; REPAIR; VITRO
AB The in vivo rodent alkaline comet assay (comet assay) is used internationally to investigate the in vivo genotoxic potential of test chemicals. This assay, however, has not previously been formally validated. The Japanese Center for the Validation of Alternative Methods (JaCVAM), with the cooperation of the U.S. NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM)/the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), the European Centre for the Validation of Alternative Methods (ECVAM), and the Japanese Environmental Mutagen Society/Mammalian Mutagenesis Study Group (JEMS/MMS), organized an international validation study to evaluate the reliability and relevance of the assay for identifying genotoxic carcinogens, using fiver and stomach as target organs. The ultimate goal of this validation effort was to establish an Organisation for Economic Co-operation and Development (OECD) test guideline. The purpose of the pre-validation studies (i.e., Phase 1 through 3), conducted in four or five laboratories with extensive comet assay experience, was to optimize the protocol to be used during the definitive validation study. (C) 2015 Elsevier B.V. All rights reserved.
C1 [Uno, Yoshifumi] Mitsubishi Tanabe Pharma Co, Chiba, Japan.
[Kojima, Hajime; Honma, Masamistu; Morita, Takeshi; Ohnob, Yasuo] Natl Inst Hlth Sci, Tokyo, Japan.
[Omori, Takashi] Kobe Univ Hosp, Kobe, Hyogo, Japan.
[Omori, Takashi] Doshisha Univ, Kyoto 602, Japan.
[Corvi, Raffaella] Commiss European Communities, Joint Res Ctr, Ispra, Italy.
[Schechtman, Leonard M.] Innovat Toxicol Consulting LLC, Lake Worth, FL USA.
[Tice, Raymond R.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA.
[Burlinson, Brian] Huntingdon Life Sci, Huntingdon, Cambs, England.
[Escobar, Patricia A.] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT USA.
[Kraynak, Andrew R.] Merck Res Labs, West Point, PA USA.
[Nakagawa, Yuzuki] Hatano Res Inst, Food Drug Safety Ctr, Kanagawa, Japan.
[Nakajima, Madoka] Univ Shizuoka, Shizuoka 4228526, Japan.
[Pant, Kamala] BioReliance, Rockville, MD USA.
[Asano, Norihide] Kinki Univ, Osaka, Japan.
[Lovell, David] Univ London, London, England.
[Hayashi, Makoto] Biosafety Res Ctr Foods Drugs & Pesticides, Shizuoka, Japan.
RP Uno, Y (reprint author), Mitsubishi Tanabe Pharma Co, Chiba, Japan.
EM Uno.Yoshifumi@ma.mt-pharma.co.jp
FU Ja-CVAM, Ministry of Health, Labor and Welfare; JEMS/MMS
FX This validation effort was conducted by financial support of JaCVAM,
Ministry of Health, Labor and Welfare, and JEMS/MMS. We are most
grateful to all colleagues of testing laboratories for their excellent
technical assistance for validation experiments.
NR 19
TC 2
Z9 2
U1 1
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1383-5718
EI 1879-3592
J9 MUTAT RES-GEN TOX EN
JI Mutat. Res. Genet. Toxicol. Environ. Mutagen.
PD JUL
PY 2015
VL 786
SI SI
BP 3
EP 13
DI 10.1016/j.mrgentox.2015.04.011
PG 11
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
GA CO9MY
UT WOS:000359501100003
PM 26212293
ER
PT J
AU Morita, T
Uno, Y
Honma, M
Kojima, H
Hayashi, M
Tice, RR
Corvi, R
Schechtman, L
AF Morita, Takeshi
Uno, Yoshifumi
Honma, Masamitsu
Kojima, Hajime
Hayashi, Makoto
Tice, Raymond R.
Corvi, Raffaella
Schechtman, Leonard
TI The JaCVAM international validation study on the in vivo comet assay:
Selection of test chemicals
SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS
LA English
DT Article
DE JaCVAM; Validation study; In vivo comet assay; Chemical selection
ID UNSCHEDULED DNA-SYNTHESIS; DISCRIMINATE RODENT CARCINOGENS; MARROW
MICRONUCLEUS ASSAY; COLLABORATIVE STUDY-GROUP; VITRO GENOTOXICITY TESTS;
MUTAGENICITY STUDY-GROUP; MOUSE MUTATION ASSAY; CENTER-DOT-MMS;
BONE-MARROW; PERIPHERAL-BLOOD
AB The Japanese Center for the Validation of Alternative Methods (JaCVAM) sponsored an international prevalidation and validation study of the in vivo rat alkaline pH comet assay. The main objective of the study was to assess the sensitivity and specificity of the assay for correctly identifying genotoxic carcinogens, as compared with the traditional rat liver unscheduled DNA synthesis assay. Based on existing carcinogenicity and genotoxicity data and chemical class information, 90 chemicals were identified as primary candidates for use in the validation study. From these 90 chemicals, 46 secondary candidates and then 40 final chemicals were selected based on a sufficiency of carcinogenic and genotoxic data, differences in chemical class or genotoxic or carcinogenic mode of action (MOA), availability, price, and ease of handling. These 40 chemicals included 19 genotoxic carcinogens, 6 genotoxic non-carcinogens, 7 non-genotoxic carcinogens and 8 non-genotoxic non-carcinogens. "Genotoxicity" was defined as positive in the Ames mutagenicity test or in one of the standard in vivo genotoxicity tests (primarily the erythrocyte micronucleus assay). These chemicals covered various chemicals classes, MOAs, and genotoxicity profiles and were considered to be suitable for the purpose of the validation study. General principles of chemical selection for validation studies are discussed. (C) 2015 Elsevier B.V. All rights reserved.
C1 [Morita, Takeshi; Honma, Masamitsu; Kojima, Hajime] Natl Inst Hlth Sci, Setagaya Ku, Tokyo 1588501, Japan.
[Uno, Yoshifumi] Mitsubishi Tanabe Pharma Co, Safety Res Labs, Chiba 2920818, Japan.
[Kojima, Hajime] JaCVAM, Setagaya Ku, Tokyo 1588501, Japan.
[Hayashi, Makoto] Publ Interest Inc Fdn, BioSafety Res Ctr, Iwata, Shizuoka 4371213, Japan.
[Tice, Raymond R.] Natl Inst Environm Hlth Sci, Div Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
[Corvi, Raffaella] Commiss European Communities, Joint Res Ctr, Inst Hlth & Consumer Protect, European Union Reference Lab Alternat Methods Ani, I-21027 Ispra, Italy.
[Schechtman, Leonard] Innovat Toxicol Consulting LLC, Lake Worth, FL 33467 USA.
RP Morita, T (reprint author), Natl Inst Hlth Sci, Setagaya Ku, 1-18-1 Kamiyoga, Tokyo 1588501, Japan.
EM morita-tk@nihs.go.jp
FU Health and Labor Sciences Research Grant [H18-Chemical-General-003,
H21-Chemical-General-004]
FX This work was supported by the Health and Labor Sciences Research Grants
(H18-Chemical-General-003 and H21-Chemical-General-004).
NR 121
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U1 3
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1383-5718
EI 1879-3592
J9 MUTAT RES-GEN TOX EN
JI Mutat. Res. Genet. Toxicol. Environ. Mutagen.
PD JUL
PY 2015
VL 786
SI SI
BP 14
EP 44
DI 10.1016/j.mrgentox.2015.03.004
PG 31
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
GA CO9MY
UT WOS:000359501100004
PM 26212294
ER
PT J
AU Uno, Y
Kojima, H
Omori, T
Corvi, R
Honma, M
Schechtman, LM
Tice, RR
Beevers, C
De Boeck, M
Burlinson, B
Hobbs, CA
Kitamoto, S
Kraynak, AR
McNamee, J
Nakagawa, Y
Pant, K
Plappert-Helbig, U
Priestley, C
Takasawa, H
Wada, K
Wirnitzert, U
Asano, N
Escobar, PA
Lovell, D
Morita, T
Nakajima, M
Ohno, Y
Hayashi, M
AF Uno, Yoshifumi
Kojima, Hajime
Omori, Takashi
Corvi, Raffaella
Honma, Masamistu
Schechtman, Leonard M.
Tice, Raymond R.
Beevers, Carol
De Boeck, Marlies
Burlinson, Brian
Hobbs, Cheryl A.
Kitamoto, Sachiko
Kraynak, Andrew R.
McNamee, James
Nakagawa, Yuzuki
Pant, Kamala
Plappert-Helbig, Ulla
Priestley, Catherine
Takasawa, Hironao
Wada, Kunio
Wirnitzert, Uta
Asano, Norihide
Escobar, Patricia A.
Lovell, David
Morita, Takeshi
Nakajima, Madoka
Ohno, Yasuo
Hayashi, Makoto
TI JaCVAM-organized international validation study of the in vivo rodent
alkaline comet assay for detection of genotoxic carcinogens: II. Summary
of definitive validation study results
SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS
LA English
DT Article
DE Comet assay; Validation study; In vivo; Rodent; Genotoxicity; JaCVAM
ID HUMAN LYMPHOBLASTOID-CELLS; LIVER MICRONUCLEUS ASSAY; CENTER-DOT-MMS;
BONE-MARROW; PERIPHERAL-BLOOD; DNA-DAMAGE; RAT-LIVER; SODIUM ARSENITE;
MULTIPLE ORGANS; MOUSE
AB The in vivo rodent alkaline comet assay (comet assay) is used internationally to investigate the in vivo genotoxic potential of test chemicals. This assay, however, has not previously been formally validated. The Japanese Center for the Validation of Alternative Methods (JaCVAM), with the cooperation of the U.S. NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM)/the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), the European Centre for the Validation of Alternative Methods (ECVAM), and the Japanese Environmental Mutagen Society/Mammalian Mutagenesis Study Group (JEMS/MMS), organized an international validation study to evaluate the reliability and relevance of the assay for identifying genotoxic carcinogens, using liver and stomach as target organs. The ultimate goal of this exercise was to establish an Organisation for Economic Co-operation and Development (OECD) test guideline. The study protocol was optimized in the pre-validation studies, and then the definitive (4th phase) validation study was conducted in two steps. In theist step, assay reproducibility was confirmed among laboratories using four coded reference chemicals and the positive control ethyl methanesulfonate. In the 2nd step, the predictive capability was investigated using 40 coded chemicals with known genotoxic and carcinogenic activity (i.e., genotoxic carcinogens, genotoxic non-carcinogens, non-genotoxic carcinogens, and non-genotoxic non-carcinogens). Based on the results obtained, the in vivo comet assay is concluded to be highly capable of identifying genotoxic chemicals and therefore can serve as a reliable predictor of rodent carcinogenicity. (C) 2015 Elsevier B.V. All rights reserved.
C1 [Uno, Yoshifumi] Mitsubishi Tanabe Pharma Co, Chiba, Japan.
[Kojima, Hajime; Honma, Masamistu; Morita, Takeshi; Ohno, Yasuo] Natl Inst Hlth Sci, Tokyo, Japan.
[Omori, Takashi] Kobe Univ Hosp, Kobe, Hyogo, Japan.
[Corvi, Raffaella] European Commiss, Joint Res Ctr, Ispra, Italy.
[Schechtman, Leonard M.] Innovat Toxicol Consulting LLC, Lake Worth, FL USA.
[Tice, Raymond R.] NIEHS, Res Triangle Pk, NC 27709 USA.
[Beevers, Carol] Covance Labs Ltd, Harrogate, N Yorkshire, England.
[De Boeck, Marlies] Janssen Res & Dev, Beerse, Belgium.
[Burlinson, Brian] Huntingdon Life Sci, Huntingdon, Cambs, England.
[Hobbs, Cheryl A.] Integrated Lab Syst Inc, Res Triangle Pk, NC USA.
[Kitamoto, Sachiko] Sumitomo Chem Co Ltd, Osaka, Japan.
[Kraynak, Andrew R.] Merck Res Labs, West Point, PA USA.
[Nakagawa, Yuzuki] Food Drug Safety Ctr, Hatano Res Inst, Hadano, Kanagawa, Japan.
[Pant, Kamala] BioReliance, Rockville, MD USA.
[Plappert-Helbig, Ulla] Novartis, Inst Biomed Res, Basel, Switzerland.
[Priestley, Catherine] AstraZeneca R&D, Macclesfield, Cheshire, England.
[Takasawa, Hironao] LSI Med, Kamisu, Ibaraki, Japan.
[Wada, Kunio] Inst Environm Toxicol, Ibaraki, Japan.
[Wirnitzert, Uta] Bayer HealthCare, Wuppertal, Germany.
[Asano, Norihide] Kinki Univ, Osaka, Japan.
[Escobar, Patricia A.] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT USA.
[Lovell, David] Univ London, London, England.
[Nakajima, Madoka] Univ Shizuoka, Shizuoka 4228526, Japan.
[Hayashi, Makoto] Biosafety Res Ctr, Foods Drugs & Pesticides, Shizuoka, Japan.
RP Uno, Y (reprint author), Mitsubishi Tanabe Pharma Co, Chiba, Japan.
EM Uno.Yoshifumi@ma.mt-pharma.co.jp
OI McNamee, James/0000-0003-2772-3455
FU JaCVAM; Ministry of Health, Labour and Welfare; JEMS/MMS
FX This validation effort was conducted by financial support of JaCVAM,
Ministry of Health, Labour and Welfare, and JEMS/MMS. We are most
grateful to all colleagues of testing laboratories for their excellent
technical assistance for validation experiments.
NR 89
TC 18
Z9 18
U1 1
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1383-5718
EI 1879-3592
J9 MUTAT RES-GEN TOX EN
JI Mutat. Res. Genet. Toxicol. Environ. Mutagen.
PD JUL
PY 2015
VL 786
SI SI
BP 45
EP 76
DI 10.1016/j.mrgentox.2015.04.010
PG 32
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
GA CO9MY
UT WOS:000359501100005
PM 26212295
ER
PT J
AU Hobbs, CA
Recio, L
Streicker, M
Boyle, MH
Tanaka, J
Shiga, A
Witt, KL
AF Hobbs, Cheryl A.
Recio, Leslie
Streicker, Michael
Boyle, Molly H.
Tanaka, Jin
Shiga, Atsushi
Witt, Kristine L.
TI Comet assay evaluation of six chemicals of known genotoxic potential in
rats
SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS
LA English
DT Article
DE In vivo comet assay; 2-Acetylaminofluorene; N-Nitrosodimethylamine;
o-Anisidine; 1,2-Dimethylhydrazine dihydrochloride; Sodium arsenite
ID CENTER-DOT-MMS; IN-VIVO; MICRONUCLEUS ASSAY; SODIUM ARSENITE;
BONE-MARROW; DNA-DAMAGE; N-NITROSOGUANIDINE; PERIPHERAL-BLOOD;
DRINKING-WATER; MOUSE ORGANS
AB As a part of an international validation of the in vivo rat alkaline comet assay (comet assay) initiated by the Japanese Center for the Validation of Alternative Methods (JaCVAM) we examined six chemicals for potential to induce DNA damage: 2-acetylaminofluorene (2-AAF), N-nitrosodimethylamine (DMN), o-anisidine, 1,2-dimethylhydrazine dihydrochloride (1,2-DMH), sodium chloride, and sodium arsenite. DNA damage was evaluated in the liver and stomach of 7- to 9-week-old male Sprague Dawley rats. Of the five genotoxic carcinogens tested in our laboratory, DMN and 1,2-DMH were positive in the liver and negative in the stomach, 2-AAF and o-anisidine produced an equivocal result in liver and negative results in stomach, and sodium arsenite was negative in both liver and stomach. 1,2-DMH and DMN induced dose-related increases in hedgehogs in the same tissue (liver) that exhibited increased DNA migration. However, no cytotoxicity was indicated by the neutral diffusion assay (assessment of highly fragmented DNA) or histopathology in response to treatment with any of the tested chemicals. Therefore, the increased DNA damage resulting from exposure to DMN and 1,2-DMH was considered to represent a genotoxic response. Sodium chloride, a non-genotoxic non-carcinogen, was negative in both tissues as would be predicted. Although only two (1,2-DMH and DMN) out of five genotoxic carcinogens produced clearly positive results in the comet assay, the results obtained for o-anisidine and sodium arsenite in liver and stomach cells are consistent with the known mode of genotoxicity and tissue specificity exhibited by these carcinogens. In contrast, given the known genotoxic mode-of-action and target organ carcinogenicity of 2-AAF, it is unclear why this chemical faller:Ito convincingly increase DNA migration in the liver. Thus, the results of the comet assay validation studies conducted in our laboratory were considered appropriate for five out of the six test chemicals. (C) 2015 Elsevier B.V. All rights reserved.
C1 [Hobbs, Cheryl A.; Recio, Leslie] Integrated Lab Syst Inc, Genet & Mol Toxicol, Res Triangle Pk, NC 27709 USA.
[Streicker, Michael] Integrated Lab Syst Inc, Invest Toxicol, Res Triangle Pk, NC 27709 USA.
[Boyle, Molly H.] Integrated Lab Syst Inc, Comparat & Mol Pathol, Res Triangle Pk, NC 27709 USA.
[Tanaka, Jin] Biosafety Res Ctr, Genotoxicol Lab, Shizuoka, Japan.
[Shiga, Atsushi] Biosafety Res Ctr, Pathol Lab, Shizuoka, Japan.
[Witt, Kristine L.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
RP Hobbs, CA (reprint author), Integrated Lab Syst Inc, POB 13501, Res Triangle Pk, NC 27709 USA.
EM chobbs@ils-inc.com
FU Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences (NIEHS) [N01-ES-35514]
FX This work was supported by the Intramural Research Program of the NIH,
National Institute of Environmental Health Sciences (NIEHS) under
contract N01-ES-35514. Although the manuscript was reviewed by NIEHS,
the statements, opinions, or conclusions contained therein do not
necessarily represent the statements, opinions, or conclusions of NIEHS,
NIH, or the United States government.
NR 49
TC 1
Z9 1
U1 1
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1383-5718
EI 1879-3592
J9 MUTAT RES-GEN TOX EN
JI Mutat. Res. Genet. Toxicol. Environ. Mutagen.
PD JUL
PY 2015
VL 786
SI SI
BP 172
EP 181
DI 10.1016/j.mrgentox.2015.03.003
PG 10
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
GA CO9MY
UT WOS:000359501100019
PM 26212309
ER
PT J
AU Abu Sayeed, M
Bufano, MK
Xu, P
Eckhoff, G
Charles, RC
Alam, MM
Sultana, T
Rashu, MR
Berger, A
Gonzalez-Escobedo, G
Mandlik, A
Bhuiyan, TR
Leung, DT
LaRocque, RC
Harris, JB
Calderwood, SB
Qadri, F
Vann, WF
Kovac, P
Ryan, ET
AF Abu Sayeed, Md.
Bufano, Meagan Kelly
Xu, Peng
Eckhoff, Grace
Charles, Richelle C.
Alam, Mohammad Murshid
Sultana, Tania
Rashu, Md. Rasheduzzaman
Berger, Amanda
Gonzalez-Escobedo, Geoffrey
Mandlik, Anjali
Bhuiyan, Taufiqur Rahman
Leung, Daniel T.
LaRocque, Regina C.
Harris, Jason B.
Calderwood, Stephen B.
Qadri, Firdausi
Vann, W. F.
Kovac, Pavol
Ryan, Edward T.
TI A Cholera Conjugate Vaccine Containing O-specific Polysaccharide (OSP)
of V. cholerae O1 Inaba and Recombinant Fragment of Tetanus Toxin Heavy
Chain (OSP:rTTHc) Induces Serum, Memory and Lamina Proprial Responses
against OSP and Is Protective in Mice
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID NEONATAL FC-RECEPTOR; B-CELL RESPONSES; FREE MOUSE MODEL;
VIBRIO-CHOLERAE; ORAL IMMUNIZATION; IMMUNE-RESPONSES; TRANSCUTANEOUS
IMMUNIZATION; CHEMOENZYMATIC SYNTHESIS; HOUSEHOLD CONTACTS;
CONTROLLED-TRIAL
AB Background
Vibrio cholerae is the cause of cholera, a severe watery diarrhea. Protection against cholera is serogroup specific. Serogroup specificity is defined by the O-specific polysaccharide (OSP) component of lipopolysaccharide (LPS).
Methodology
Here we describe a conjugate vaccine for cholera prepared via squaric acid chemistry from the OSP of V. cholerae O1 Inaba strain PIC018 and a recombinant heavy chain fragment of tetanus toxin (OSP:rTTHc). We assessed a range of vaccine doses based on the OSP content of the vaccine (10-50 mu g), vaccine compositions varying by molar loading ratio of OSP to rTTHc (3:1, 5:1, 10:1), effect of an adjuvant, and route of immunization.
Principle Findings
Immunized mice developed prominent anti-OSP and anti-TT serum IgG responses, as well as vibriocidal antibody and memory B cell responses following intramuscular or intradermal vaccination. Mice did not develop anti-squarate responses. Intestinal lamina proprial IgA responses targeting OSP occurred following intradermal vaccination. In general, we found comparable immune responses in mice immunized with these variations, although memory B cell and vibriocidal responses were blunted in mice receiving the highest dose of vaccine (50 mu g). We found no appreciable change in immune responses when the conjugate vaccine was administered in the presence or absence of immunoadjuvant alum. Administration of OSP:rTTHc resulted in 55% protective efficacy in a mouse survival cholera challenge model.
Conclusion
We report development of an Inaba OSP:rTTHc conjugate vaccine that induces memory responses and protection against cholera in mice. Development of an effective cholera conjugate vaccine that induces high level and long-term immune responses against OSP would be beneficial, especially in young children who respond poorly to polysaccharide antigens.
C1 [Abu Sayeed, Md.; Bufano, Meagan Kelly; Alam, Mohammad Murshid; Sultana, Tania; Rashu, Md. Rasheduzzaman; Berger, Amanda; Gonzalez-Escobedo, Geoffrey; Mandlik, Anjali; Bhuiyan, Taufiqur Rahman; Leung, Daniel T.; LaRocque, Regina C.; Harris, Jason B.; Calderwood, Stephen B.; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Abu Sayeed, Md.; Alam, Mohammad Murshid; Sultana, Tania; Rashu, Md. Rasheduzzaman; Bhuiyan, Taufiqur Rahman; Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Ctr Vaccine Sci, Dhaka, Bangladesh.
[Xu, Peng] Natl Inst Diabet Digest & Kidney Dis NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD USA.
[Eckhoff, Grace; Charles, Richelle C.; Kovac, Pavol; Ryan, Edward T.] Harvard Univ, Sch Med, Boston, MA USA.
[Leung, Daniel T.] Univ Utah, Sch Med, Div Infect Dis, Salt Lake City, UT USA.
[Harris, Jason B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA.
[Vann, W. F.] US FDA, Ctr Biol Evaluat & Res, Lab Bacterial Toxins, Bethesda, MD USA.
[Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
RP Abu Sayeed, M (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
EM etryan@mgh.harvard.edu
RI Kovac, Pavol/B-8813-2008; Xu, Peng/K-7036-2012
OI Kovac, Pavol/0000-0001-5044-3449;
FU National Institutes of Health; National Institute of Allergy and
Infectious Diseases [UO1 AI106878, U01 AI058935, K08 AI089721]; Fogarty
International Center [TW005572]; NIH; NIDDK
FX This research was supported by core grants to the icddr,b and through
programs funded by the National Institutes of Health, including the
National Institute of Allergy and Infectious Diseases (UO1 AI106878 [ETR
and FQ], U01 AI058935 [SBC, FQ and ETR], and K08 AI089721 [RCC]), the
Fogarty International Center, Training Grant in Vaccine Development and
Public Health (TW005572 [MAS, MMA, TS, MRR, TRB and FQ]), and the
Intramural Research Program of the NIH and NIDDK (PX and PK). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 54
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U1 3
U2 13
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1935-2735
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD JUL
PY 2015
VL 9
IS 7
AR e0003881
DI 10.1371/journal.pntd.0003881
PG 18
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA CO3SM
UT WOS:000359079700013
ER
PT J
AU Campbell, KM
Haldeman, K
Lehnig, C
Munayco, CV
Halsey, ES
Laguna-Torres, VA
Yagui, M
Morrison, AC
Lin, CD
Scott, TW
AF Campbell, Karen M.
Haldeman, Kristin
Lehnig, Chris
Munayco, Cesar V.
Halsey, Eric S.
Laguna-Torres, V. Alberto
Yagui, Martin
Morrison, Amy C.
Lin, Chii-Dean
Scott, Thomas W.
TI Weather Regulates Location, Timing, and Intensity of Dengue Virus
Transmission between Humans and Mosquitoes
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID AEDES-AEGYPTI DIPTERA; TEMPERATURE-FLUCTUATIONS; PUERTO-RICO; GLOBAL
DISTRIBUTION; MODEL DEVELOPMENT; HUMAN MOVEMENT; BORNE DISEASE;
THAILAND; CLIMATE; CULICIDAE
AB Background
Dengue is one of the most aggressively expanding mosquito-transmitted viruses. The human burden approaches 400 million infections annually. Complex transmission dynamics pose challenges for predicting location, timing, and magnitude of risk; thus, models are needed to guide prevention strategies and policy development locally and globally. Weather regulates transmission-potential via its effects on vector dynamics. An important gap in understanding risk and roadblock in model development is an empirical perspective clarifying how weather impacts transmission in diverse ecological settings. We sought to determine if location, timing, and potential-intensity of transmission are systematically defined by weather.
Methodology/Principal Findings
We developed a high-resolution empirical profile of the local weather-disease connection across Peru, a country with considerable ecological diversity. Applying 2-dimensional weather-space that pairs temperature versus humidity, we mapped local transmission-potential in weather-space by week during 1994-2012. A binary classification-tree was developed to test whether weather data could classify 1828 Peruvian districts as positive/negative for transmission and into ranks of transmission-potential with respect to observed disease. We show that transmission-potential is regulated by temperature-humidity coupling, enabling epidemics in a limited area of weather-space. Duration within a specific temperature range defines transmission-potential that is amplified exponentially in higher humidity. Dengue-positive districts were identified by mean temperature >22 degrees C for 7+ weeks and minimum temperature >14 degrees C for 33+ weeks annually with 95% sensitivity and specificity. In elevated-risk locations, seasonal peak-incidence occurred when mean temperature was 26-29 degrees C, coincident with humidity at its local maximum; highest incidence when humidity >80%. We profile transmission-potential in weather-space for temperature-humidity ranging 0-38 degrees C and 5-100% at 1 degrees C x 2% resolution.
Conclusions/Significance Local duration in limited areas of temperature-humidity weather-space identifies potential locations, timing, and magnitude of transmission. The weather-space profile of transmission-potential provides needed data that define a systematic and highly-sensitive weather-disease connection, demonstrating separate but coupled roles of temperature and humidity. New insights regarding natural regulation of human-mosquito transmission across diverse ecological settings advance our understanding of risk locally and globally for dengue and other mosquito-borne diseases and support advances in public health policy/operations, providing an evidence-base for modeling, predicting risk, and surveillance-prevention planning.
C1 [Campbell, Karen M.; Haldeman, Kristin; Lehnig, Chris] San Diego State Univ, Computat Sci Res Ctr, San Diego, CA 92182 USA.
[Munayco, Cesar V.] Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA.
[Halsey, Eric S.] US Naval Med Res Unit 6, Lima, Peru.
[Laguna-Torres, V. Alberto; Yagui, Martin] Direcc Gen Epidemiol, Lima, Peru.
[Morrison, Amy C.; Scott, Thomas W.] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA.
[Lin, Chii-Dean] San Diego State Univ, Dept Math & Stat, San Diego, CA 92182 USA.
[Scott, Thomas W.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Campbell, KM (reprint author), San Diego State Univ, Computat Sci Res Ctr, San Diego, CA 92182 USA.
EM kmca@roadrunner.com
FU Bill & Melinda Gates Foundation [OPP52250]; Research and Policy for
Infectious Disease Dynamics (RAPIDD) program of the Science and
Technology Directory, Department of Homeland Security; Fogarty
International Center, National Institutes of Health
FX This work was supported by the Bill & Melinda Gates Foundation
(OPP52250). TWS acknowledges funding from 3, and Fogarty International
Center, National Institutes of Health. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 50
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U1 4
U2 28
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1935-2735
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD JUL
PY 2015
VL 9
IS 7
AR e0003957
DI 10.1371/journal.pntd.0003957
PG 26
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA CO3SM
UT WOS:000359079700054
PM 26222979
ER
PT J
AU Deribe, K
Cano, J
Newport, MJ
Golding, N
Pullan, RL
Sime, H
Gebretsadik, A
Assefa, A
Kebede, A
Hailu, A
Rebollo, MP
Shafi, O
Bockarie, MJ
Aseffa, A
Hay, SI
Reithinger, R
Enquselassie, F
Davey, G
Brooker, SJ
AF Deribe, Kebede
Cano, Jorge
Newport, Melanie J.
Golding, Nick
Pullan, Rachel L.
Sime, Heven
Gebretsadik, Abeba
Assefa, Ashenafi
Kebede, Amha
Hailu, Asrat
Rebollo, Maria P.
Shafi, Oumer
Bockarie, Moses J.
Aseffa, Abraham
Hay, Simon I.
Reithinger, Richard
Enquselassie, Fikre
Davey, Gail
Brooker, Simon J.
TI Mapping and Modelling the Geographical Distribution and Environmental
Limits of Podoconiosis in Ethiopia
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID NON-FILARIAL ELEPHANTIASIS; LOWER LEGS; ENDEMIC ELEPHANTIASIS;
BANCROFTIAN FILARIASIS; LYMPHATIC FILARIASIS; GLOBAL DISTRIBUTION;
SOUTHERN ETHIOPIA; WESTERN ETHIOPIA; HIGH PREVALENCE; EAST-AFRICA
AB Background
Ethiopia is assumed to have the highest burden of podoconiosis globally, but the geographical distribution and environmental limits and correlates are yet to be fully investigated. In this paper we use data from a nationwide survey to address these issues.
Methodology
Our analyses are based on data arising from the integrated mapping of podoconiosis and lymphatic filariasis (LF) conducted in 2013, supplemented by data from an earlier mapping of LF in western Ethiopia in 2008-2010. The integrated mapping used woreda (district) health offices' reports of podoconiosis and LF to guide selection of survey sites. A suite of environmental and climatic data and boosted regression tree (BRT) modelling was used to investigate environmental limits and predict the probability of podoconiosis occurrence.
Principal Findings
Data were available for 141,238 individuals from 1,442 communities in 775 districts from all nine regional states and two city administrations of Ethiopia. In 41.9% of surveyed districts no cases of podoconiosis were identified, with all districts in Affar, Dire Dawa, Somali and Gambella regional states lacking the disease. The disease was most common, with lymphoedema positivity rate exceeding 5%, in the central highlands of Ethiopia, in Amhara, Oromia and Southern Nations, Nationalities and Peoples regional states. BRT modelling indicated that the probability of podoconiosis occurrence increased with increasing altitude, precipitation and silt fraction of soil and decreased with population density and clay content. Based on the BRT model, we estimate that in 2010, 34.9 (95% confidence interval [CI]: 20.2-51.7) million people (i.e. 43.8%; 95% CI: 25.3-64.8% of Ethiopia's national population) lived in areas environmentally suitable for the occurrence of podoconiosis.
Conclusions
Podoconiosis is more widespread in Ethiopia than previously estimated, but occurs in distinct geographical regions that are tied to identifiable environmental factors. The resultant maps can be used to guide programme planning and implementation and estimate disease burden in Ethiopia. This work provides a framework with which the geographical limits of podoconiosis could be delineated at a continental scale.
C1 [Deribe, Kebede; Newport, Melanie J.; Davey, Gail] Brighton & Sussex Med Sch, Brighton, E Sussex, England.
[Deribe, Kebede; Enquselassie, Fikre] Univ Addis Ababa, Sch Publ Hlth, Addis Ababa, Ethiopia.
[Cano, Jorge; Pullan, Rachel L.; Reithinger, Richard; Brooker, Simon J.] London Sch Hyg & Trop Med, Fac Infect & Trop Dis, London WC1, England.
[Golding, Nick; Hay, Simon I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Sime, Heven; Gebretsadik, Abeba; Assefa, Ashenafi; Kebede, Amha] Ethiopian Publ Hlth Inst, Addis Ababa, Ethiopia.
[Hailu, Asrat] Univ Addis Ababa, Sch Med, Addis Ababa, Ethiopia.
[Rebollo, Maria P.; Bockarie, Moses J.] Univ Liverpool, Liverpool Sch Trop Med, Ctr Neglected Trop Dis, Liverpool L3 5QA, Merseyside, England.
[Shafi, Oumer] Fed Minist Hlth, Addis Ababa, Ethiopia.
[Aseffa, Abraham] Armauer Hansen Res Inst ALERT, Addis Ababa, Ethiopia.
[Hay, Simon I.] Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
[Hay, Simon I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Reithinger, Richard] RTI Int, Washington, DC USA.
RP Deribe, K (reprint author), Brighton & Sussex Med Sch, Brighton, E Sussex, England.
EM kebededeka@yahoo.com
RI Hay, Simon/F-8967-2015; Aseffa, Abraham/J-3248-2016;
OI Hay, Simon/0000-0002-0611-7272; Aseffa, Abraham/0000-0002-8028-1150;
Golding, Nick/0000-0001-8916-5570; Deribe, Kebede/0000-0002-8526-6996
FU Wellcome Trust [099876, 091956, 098045, 095066]; Bill & Melinda Gates
Foundation [OPP1093011]; RAPIDD program of the Science & Technology
Directorate, Department of Homeland Security; Fogarty International
Center, National Institutes of Health
FX This study was financially supported by The Wellcome Trust [grant number
099876]. KD is supported by a Wellcome Trust Fellowship in Public Health
and Tropical Medicine [grant number 099876]. GD is supported by a
Wellcome Trust University award [grant number 091956] to do work in
podoconiosis. SJB is supported by a Wellcome Trust Senior Fellowship in
Basic Biomedical Science [grant number 098045], which also supports RLP
and the Global Atlas of Helminth Infections (www.thiswormyworld.org).
SIH is funded by a Senior Research Fellowship from the Wellcome Trust
(#095066), which also supports NG and a grant from the Bill & Melinda
Gates Foundation (#OPP1093011). SIH would also like to acknowledge
funding support from the RAPIDD program of the Science & Technology
Directorate, Department of Homeland Security, and the Fogarty
International Center, National Institutes of Health. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 64
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U1 1
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1935-2735
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD JUL
PY 2015
VL 9
IS 7
AR e0003946
DI 10.1371/journal.pntd.0003946
PG 18
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA CO3SM
UT WOS:000359079700048
PM 26222887
ER
PT J
AU Cortez, V
Wang, BJ
Dingens, A
Chen, MM
Ronen, K
Georgiev, IS
McClelland, RS
Overbaugh, J
AF Cortez, Valerie
Wang, Bingjie
Dingens, Adam
Chen, Mitchell M.
Ronen, Keshet
Georgiev, Ivelin S.
McClelland, R. Scott
Overbaugh, Julie
TI The Broad Neutralizing Antibody Responses after HIV-1 Superinfection Are
Not Dominated by Antibodies Directed to Epitopes Common in Single
Infection
SO PLOS PATHOGENS
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; B-CELL RESPONSES; MONOCLONAL-ANTIBODIES;
VACCINE DEVELOPMENT; HIV-1-INFECTED INDIVIDUALS; GP41-GP120 INTERFACE;
DEPENDENT EPITOPE; BINDING-SITE; CD4 BINDING; ENVELOPE
AB HIV-1 vaccines designed to date have failed to elicit neutralizing antibodies (Nabs) that are capable of protecting against globally diverse HIV-1 subtypes. One relevant setting to study the development of a strong, cross-reactive Nab response is HIV-1 superinfection (SI), defined as sequential infections from different source partners. SI has previously been shown to lead to a broader and more potent Nab response when compared to single infection, but it is unclear whether SI also impacts epitope specificity and if the epitopes targeted after SI differ from those targeted after single infection. Here the post-SI Nab responses were examined from 21 Kenyan women collectively exposed to subtypes A, C, and D and superinfected after a median time of similar to 1.07 years following initial infection. Plasma samples chosen for analysis were collected at a median time point similar to 2.72 years post-SI. Because previous studies of singly infected populations with broad and potent Nab responses have shown that the majority of their neutralizing activity can be mapped to 4 main epitopes on the HIV-1 Envelope, we focused on these targets, which include the CD4-binding site, a V1/V2 glycan, the N332 supersite in V3, and the membrane proximal external region of gp41. Using standard epitope mapping techniques that were applied to the previous cohorts, the present study demonstrates that SI did not induce a dominant Nab response to any one of these epitopes in the 21 women. Computational sera delineation analyses also suggested that 20 of the 21 superinfected women's Nab responses could not be ascribed a single specificity with high confidence. These data are consistent with a model in which SI with diverse subtypes promotes the development of a broad polyclonal Nab response, and thus would provide support for vaccine designs using multivalent HIV immunogens to elicit a diverse repertoire of Nabs.
C1 [Cortez, Valerie; Dingens, Adam] Univ Washington, Program Mol & Cellular Biol, Seattle, WA 98195 USA.
[Cortez, Valerie; Wang, Bingjie; Dingens, Adam; Chen, Mitchell M.; Ronen, Keshet; Overbaugh, Julie] Fred Hutchinson Canc Res Ctr, Human Biol Div, Seattle, WA 98104 USA.
[Georgiev, Ivelin S.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA.
[McClelland, R. Scott] Univ Washington, Dept Med, Seattle, WA USA.
RP Overbaugh, J (reprint author), Fred Hutchinson Canc Res Ctr, Human Biol Div, 1124 Columbia St, Seattle, WA 98104 USA.
EM joverbau@fhcrc.org
OI Dingens, Adam/0000-0001-9603-9409
FU National Institutes of Health [R01 AI103981, R37 AI038518, T32 AI714036]
FX Funding: The study was funded by the National Institutes of Health R01
AI103981 and R37 AI038518 awarded to JO and T32 AI714036 awarded to VC.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 66
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U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD JUL
PY 2015
VL 11
IS 7
AR e1004973
DI 10.1371/journal.ppat.1004973
PG 24
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA CO7TQ
UT WOS:000359365200016
PM 26158467
ER
PT J
AU Davis, DA
Naiman, NE
Wang, V
Shrestha, P
Haque, M
Hu, DS
Anagho, HA
Carey, RF
Davidoff, KS
Yarchoan, R
AF Davis, David A.
Naiman, Nicole E.
Wang, Victoria
Shrestha, Prabha
Haque, Muzammel
Hu, Duosha
Anagho, Holda A.
Carey, Robert F.
Davidoff, Katharine S.
Yarchoan, Robert
TI Identification of Caspase Cleavage Sites in KSHV Latency-Associated
Nuclear Antigen and Their Effects on Caspase-Related Host Defense
Responses
SO PLOS PATHOGENS
LA English
DT Article
ID SARCOMA-ASSOCIATED HERPESVIRUS; EPSTEIN-BARR-VIRUS; ENDOTHELIAL-CELLS;
VIRAL-INFECTION; PROTEIN; APOPTOSIS; INFLAMMASOMES; ACTIVATION; HOMOLOG;
REPLICATION
AB Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus-8, is the causative agent of three hyperproliferative disorders: Kaposi's sarcoma, primary effusion lymphoma (PEL) and multicentric Castleman's disease. During viral latency a small subset of viral genes are produced, including KSHV latency-associated nuclear antigen (LANA), which help the virus thwart cellular defense responses. We found that exposure of KSHV-infected cells to oxidative stress, or other inducers of apoptosis and caspase activation, led to processing of LANA and that this processing could be inhibited with the pan-caspase inhibitor Z-VAD-FMK. Using sequence, peptide, and mutational analysis, two caspase cleavage sites within LANA were identified: a site for caspase-3 type caspases at the N-terminus and a site for caspase-1 and -3 type caspases at the C-terminus. Using LANA expression plasmids, we demonstrated that mutation of these cleavage sites prevents caspase-1 and caspase-3 processing of LANA. This indicates that these are the principal sites that are susceptible to caspase cleavage. Using peptides spanning the identified LANA cleavage sites, we show that caspase activity can be inhibited in vitro and that a cell-permeable peptide spanning the C-terminal cleavage site could inhibit cleavage of poly (ADP-ribose) polymerase and increase viability in cells undergoing etoposide-induced apoptosis. The C-terminal peptide of LANA also inhibited interleukin-1beta (IL-1 beta) production from lipopoly-saccharide-treated THP-1 cells by more than 50%. Furthermore, mutation of the two cleavage sites in LANA led to a significant increase in IL-1 beta production in transfected THP-1 cells; this provides evidence that these sites function to blunt the inflammasome, which is known to be activated in latently infected PEL cells. These results suggest that specific caspase cleavage sites in KSHV LANA function to blunt apoptosis as well as interfere with the caspase-1-mediated inflammasome, thus thwarting key cellular defense mechanisms.
C1 [Davis, David A.; Naiman, Nicole E.; Wang, Victoria; Shrestha, Prabha; Haque, Muzammel; Hu, Duosha; Anagho, Holda A.; Carey, Robert F.; Davidoff, Katharine S.; Yarchoan, Robert] NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Davis, DA (reprint author), NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
EM dadavis@helix.nih.gov
NR 52
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U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD JUL
PY 2015
VL 11
IS 7
AR e1005064
DI 10.1371/journal.ppat.1005064
PG 23
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA CO7TQ
UT WOS:000359365200066
PM 26218605
ER
PT J
AU Gilman, MSA
Moin, SM
Mas, V
Chen, M
Patel, NK
Kramer, K
Zhu, Q
Kabeche, SC
Kumar, A
Palomo, C
Beaumont, T
Baxa, U
Ulbrandt, ND
Melero, JA
Graham, BS
McLellan, JS
AF Gilman, Morgan S. A.
Moin, Syed M.
Mas, Vicente
Chen, Man
Patel, Nita K.
Kramer, Kari
Zhu, Qing
Kabeche, Stephanie C.
Kumar, Azad
Palomo, Concepcion
Beaumont, Tim
Baxa, Ulrich
Ulbrandt, Nancy D.
Melero, Jose A.
Graham, Barney S.
McLellan, Jason S.
TI Characterization of a Prefusion-Specific Antibody That Recognizes a
Quaternary, Cleavage-Dependent Epitope on the RSV Fusion Glycoprotein
SO PLOS PATHOGENS
LA English
DT Article
ID RESPIRATORY-SYNCYTIAL-VIRUS; HUMAN MONOCLONAL-ANTIBODY; 2 DISTINCT
SITES; NEUTRALIZING ANTIBODY; INTRACELLULAR-TRANSPORT; GP41-GP120
INTERFACE; STRUCTURAL BASIS; F-GLYCOPROTEIN; IN-VITRO; PROTEIN
AB Prevention efforts for respiratory syncytial virus (RSV) have been advanced due to the recent isolation and characterization of antibodies that specifically recognize the prefusion conformation of the RSV fusion (F) glycoprotein. These potently neutralizing antibodies are in clinical development for passive prophylaxis and have also aided the design of vaccine antigens that display prefusion-specific epitopes. To date, prefusion-specific antibodies have been shown to target two antigenic sites on RSV F, but both of these sites are also present on monomeric forms of F. Here we present a structural and functional characterization of human antibody AM14, which potently neutralized laboratory strains and clinical isolates of RSV from both A and B subtypes. The crystal structure and location of escape mutations revealed that AM14 recognizes a quaternary epitope that spans two protomers and includes a region that undergoes extensive conformational changes in the pre- to post-fusion F transition. Binding assays demonstrated that AM14 is unique in its specific recognition of trimeric furin-cleaved prefusion F, which is the mature form of F on infectious virions. These results demonstrate that the prefusion F trimer contains potent neutralizing epitopes not present on monomers and that AM14 should be particularly useful for characterizing the conformational state of RSV F-based vaccine antigens.
C1 [Gilman, Morgan S. A.; Kabeche, Stephanie C.; McLellan, Jason S.] Geisel Sch Med Dartmouth, Dept Biochem, Hanover, NH 03755 USA.
[Moin, Syed M.; Chen, Man; Kumar, Azad; Graham, Barney S.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Mas, Vicente; Palomo, Concepcion; Melero, Jose A.] Inst Salud Carlos III, Ctr Nacl Microbiol, Madrid, Spain.
[Mas, Vicente; Palomo, Concepcion; Melero, Jose A.] Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain.
[Patel, Nita K.; Kramer, Kari; Zhu, Qing; Ulbrandt, Nancy D.] Medimmune Inc, Gaithersburg, MD 20878 USA.
[Beaumont, Tim] Univ Amsterdam, Acad Med Ctr, AIMM Therapeut, NL-1105 AZ Amsterdam, Netherlands.
[Baxa, Ulrich] Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, Canc Res Technol Program, Electron Microscopy Lab, Frederick, MD USA.
RP McLellan, JS (reprint author), Geisel Sch Med Dartmouth, Dept Biochem, Hanover, NH 03755 USA.
EM Jason.S.McLellan@Dartmouth.edu
RI Mas, Vicente/M-4776-2015
OI Mas, Vicente/0000-0002-0887-0743
FU NSF & NIH/NIGMS via NSF award [DMR-1332208]; NIH/NIGMS [GM-103485]; U.S.
Department of Energy, Office of Biological and Environmental Research
[DE-AC02-06CH11357]; Frederick National Laboratory for Cancer Research,
National Institutes of Health [HHSN261200800001E]; MedImmune Inc; "Plan
Nacional I+D+I" (Ministerio de Economia y Competitividad)
[SAF2012-31217]; National Institute of Allergy and Infectious Diseases;
National Institutes of Health [1R43AI112124]
FX Data collection at CHESS is supported by the NSF & NIH/NIGMS via NSF
award DMR-1332208, and the MacCHESS resource is supported by NIH/NIGMS
award GM-103485. Results shown in this report were also derived from
work performed at Argonne National Laboratory, Structural Biology Center
at the Advanced Photon Source. Argonne is operated by UChicago Argonne,
LLC, for the U.S. Department of Energy, Office of Biological and
Environmental Research under contract DE-AC02-06CH11357. Work performed
by UB was funded in part with Federal funds from the Frederick National
Laboratory for Cancer Research, National Institutes of Health, under
contract HHSN261200800001E. NKP, KK, QZ and NDU were employed by
MedImmune Inc, which funded the data collection and analysis of their
experiments (neutralization assays, MARM isolation and affinity of D25
for peptide). JAM received funding from "Plan Nacional I+D+I"
(Ministerio de Economia y Competitividad), grant SAF2012-31217. BSG was
supported by funding from the intramural program of the National
Institute of Allergy and Infectious Diseases. JSM received funding from
the National Institutes of Health, grant 1R43AI112124. With the
exception of MedImmune's involvement stated above, the funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 52
TC 26
Z9 26
U1 33
U2 37
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD JUL
PY 2015
VL 11
IS 7
AR e1005035
DI 10.1371/journal.ppat.1005035
PG 17
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA CO7TQ
UT WOS:000359365200047
PM 26161532
ER
PT J
AU Li, QX
Wilkie, AR
Weller, M
Liu, XQ
Cohen, JI
AF Li, Qingxue
Wilkie, Adrian R.
Weller, Melodie
Liu, Xueqiao
Cohen, Jeffrey I.
TI THY-1 Cell Surface Antigen (CD90) Has an Important Role in the Initial
Stage of Human Cytomegalovirus Infection
SO PLOS PATHOGENS
LA English
DT Article
ID GROWTH-FACTOR RECEPTOR; GLYCOPROTEIN COMPLEX GB; DISINTEGRIN-LIKE
DOMAIN; HERPES-SIMPLEX-VIRUS; SMOOTH-MUSCLE-CELLS; DESIGNATED GC-II;
ENDOTHELIAL-CELLS; EPITHELIAL-CELLS; HUMAN FIBROBLASTS; ZAIRE-EBOLAVIRUS
AB Human cytomegalovirus (HCMV) infects about 50% of the US population, is the leading infectious cause of birth defects, and is considered the most important infectious agent in transplant recipients. The virus infects many cell types in vivo and in vitro. While previous studies have identified several cellular proteins that may function at early steps of infection in a cell type dependent manner, the mechanism of virus entry is still poorly understood. Using a computational biology approach, correlating gene expression with virus infectivity in 54 cell lines, we identified THY-1 as a putative host determinant for HCMV infection in these cells. With a series of loss-of-function, gain-of-function and protein-protein interaction analyses, we found that THY-1 mediates HCMV infection at the entry step and is important for infection that occurs at a low m.o.i. THY-1 antibody that bound to the cell surface blocked HCMV during the initial 60 minutes of infection in a dose-dependent manner. Down-regulation of THY-1 with siRNA impaired infectivity occurred during the initial 60 minutes of inoculation. Both THY-1 antibody and siRNA inhibited HCMV-induced activation of the PI3-K/Akt pathway required for entry. Soluble THY-1 protein blocked HCMV infection during, but not after, virus internalization. Expression of exogenous THY-1 enhanced entry in cells expressing low levels of the protein. THY-1 interacted with HCMV gB and gH and may form a complex important for entry. However, since gB and gH have previously been shown to interact, it is uncertain if THY-1 directly binds to both of these proteins. Prior observations that THY-1 (a) interacts with alpha V beta 3 integrin and recruits paxillin (implicated in HCMV entry), (b) regulates leukocyte extravasation (critical for HCMV viremia), and (c) is expressed on many cells targeted for HCMV infection including epithelial and endothelial cells, fibroblast, and CD34+/CD38- stem cells, all support a role for THY-1 as an HCMV entry mediator in a cell type dependent manner. THY-1 may function through a complex setting, that would include viral gB and gH, and other cellular factors, thus links virus entry with signaling in host cells that ultimately leads to virus infection.
C1 [Li, Qingxue; Wilkie, Adrian R.; Liu, Xueqiao; Cohen, Jeffrey I.] NIH, Med Virol Sect, Infect Dis Lab, Bethesda, MD 20892 USA.
[Weller, Melodie] NIH, Secretory Physiol Sect, Mol Physiol & Therapeut Branch, Bethesda, MD 20892 USA.
RP Cohen, JI (reprint author), NIH, Med Virol Sect, Infect Dis Lab, Bldg 10, Bethesda, MD 20892 USA.
EM jcohen@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases
FX Funding: This work was supported by the intramural research program of
the National Institute of Allergy and Infectious Diseases. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 89
TC 6
Z9 6
U1 1
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD JUL
PY 2015
VL 11
IS 7
AR e1004999
DI 10.1371/journal.ppat.1004999
PG 26
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA CO7TQ
UT WOS:000359365200025
PM 26147640
ER
PT J
AU Pollitt, LC
Bram, JT
Blanford, S
Jones, MJ
Read, AF
AF Pollitt, Laura C.
Bram, Joshua T.
Blanford, Simon
Jones, Matthew J.
Read, Andrew F.
TI Existing Infection Facilitates Establishment and Density of Malaria
Parasites in Their Mosquito Vector
SO PLOS PATHOGENS
LA English
DT Article
ID RESISTANT PLASMODIUM-FALCIPARUM; ANOPHELES-GAMBIAE; DRUG-RESISTANCE;
WESTERN KENYA; TRANSMISSION; POPULATION; EVOLUTION; VIRULENCE;
COMPETITION; BLOOD
AB Very little is known about how vector-borne pathogens interact within their vector and how this impacts transmission. Here we show that mosquitoes can accumulate mixed strain malaria infections after feeding on multiple hosts. We found that parasites have a greater chance of establishing and reach higher densities if another strain is already present in a mosquito. Mixed infections contained more parasites but these larger populations did not have a detectable impact on vector survival. Together these results suggest that mosquitoes taking multiple infective bites may disproportionally contribute to malaria transmission. This will increase rates of mixed infections in vertebrate hosts, with implications for the evolution of parasite virulence and the spread of drug-resistant strains. Moreover, control measures that reduce parasite prevalence in vertebrate hosts will reduce the likelihood of mosquitoes taking multiple infective feeds, and thus disproportionally reduce transmission. More generally, our study shows that the types of strain interactions detected in vertebrate hosts cannot necessarily be extrapolated to vectors.
C1 [Pollitt, Laura C.] Univ Edinburgh, Ctr Immun Infect & Evolut, Edinburgh, Midlothian, Scotland.
[Pollitt, Laura C.; Bram, Joshua T.; Blanford, Simon; Jones, Matthew J.; Read, Andrew F.] Penn State Univ, Ctr Infect Dis Dynam, Dept Biol, State Coll, PA USA.
[Pollitt, Laura C.; Bram, Joshua T.; Blanford, Simon; Jones, Matthew J.; Read, Andrew F.] Penn State Univ, Ctr Infect Dis Dynam, Dept Entomol, State Coll, PA USA.
[Read, Andrew F.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Pollitt, LC (reprint author), Univ Edinburgh, Ctr Immun Infect & Evolut, Edinburgh, Midlothian, Scotland.
EM laura.pollitt@gmail.com
FU Institute of General Medical Science of the National Institutes of
Health [R01 GM089932]; Wellcome Trust Centre for Infection, Immunology
and Evolution at the University of Edinburgh; Eberly College of Science
Undergraduate Research Grant from Pennsylvania State University
FX Funding: This study was funded by the Institute of General Medical
Science (R01 GM089932 to AFR) of the National Institutes of Health. LCP
was also supported by a fellowship from the Wellcome Trust Centre for
Infection, Immunology and Evolution at the University of Edinburgh. JTB
was supported by an Eberly College of Science Undergraduate Research
Grant from the Pennsylvania State University. The funders had no role in
study design, data collection and analysis, decision to publish or the
preparation of the manuscript.
NR 59
TC 3
Z9 3
U1 2
U2 21
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD JUL
PY 2015
VL 11
IS 7
AR e1005003
DI 10.1371/journal.ppat.1005003
PG 18
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA CO7TQ
UT WOS:000359365200027
PM 26181518
ER
PT J
AU Ortiz, J
Hofler, RA
Lin, YL
Berzon, R
AF Ortiz, Judith
Hofler, Richard A.
Lin, Yi-Ling
Berzon, Richard
TI Participation of Rural Health Care Providers in Accountable Care
Organizations Early Indications
SO HEALTH CARE MANAGER
LA English
DT Article
DE accountable care organizations; primary health care; rural health
AB Recently, some rural health clinics (RHCs) throughout the country have chosen to join groups of health care providers in accountable care organizations (ACOs). Examined are characteristics of Southeastern RHCs and the counties they serve; it is shown how those characteristics compare with other regions across the country and suggested what role those differences might play in an RHC's decision to participate in an ACO. Rural health clinic-related data were collected and summarized for 2 time periods: 2007 and 2011: for 2007, data from RHCs throughout the United States; for 2011, summarized demographic data related to region 4 RHCs specifically. Several characteristics about region 4 RHCs indicate that they may be slow to participate in ACOs. However, other characteristics, including their perception that ACOs may improve the quality of care and health outcomes of their patients and communities, may facilitate the process of RHCs joining ACOs, should they choose to do so. Addressing the health care needs and health care quality of rural populations must be part of the design, development, and performance monitoring of ACOs of the future.
C1 [Ortiz, Judith; Lin, Yi-Ling] Univ Cent Florida, Coll Hlth & Publ Affairs, Orlando, FL 32816 USA.
[Hofler, Richard A.] Univ Cent Florida, Coll Business Adm, Orlando, FL 32816 USA.
[Berzon, Richard] Natl Inst Minor Hlth & Hlth Dispar, Div Sci Programs, NIH, Bethesda, MD USA.
RP Ortiz, J (reprint author), Univ Cent Florida, Coll Hlth & Publ Affairs, POB 162369, Orlando, FL 32816 USA.
EM Judith.Ortiz@ucf.edu
FU NIMHD NIH HHS [U24 MD006954, U24MD006954]
NR 12
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1525-5794
EI 1550-512X
J9 HEALTH CARE MANAG
JI Health Care Manag.
PD JUL-SEP
PY 2015
VL 34
IS 3
BP 255
EP 264
DI 10.1097/HCM.0000000000000069
PG 10
WC Health Policy & Services
SC Health Care Sciences & Services
GA CO8AL
UT WOS:000359386800012
PM 26218001
ER
PT J
AU Mitragotri, S
Anderson, DG
Chen, XY
Chow, EK
Ho, D
Kabanov, AV
Karp, JM
Kataoka, K
Mirkin, CA
Petrosko, SH
Shi, JJ
Stevens, MM
Sun, SH
Teoh, S
Venkatraman, SS
Xia, YN
Wang, ST
Gu, Z
Xu, CJ
AF Mitragotri, Samir
Anderson, Daniel G.
Chen, Xiaoyuan
Chow, Edward K.
Ho, Dean
Kabanov, Alexander V.
Karp, Jeffrey M.
Kataoka, Kazunori
Mirkin, Chad A.
Petrosko, Sarah Hurst
Shi, Jinjun
Stevens, Molly M.
Sun, Shouheng
Teoh, Sweehin
Venkatraman, Subbu S.
Xia, Younan
Wang, Shutao
Gu, Zhen
Xu, Chenjie
TI Accelerating the Translation of Nanomaterials in Biomedicine
SO ACS NANO
LA English
DT Article
ID SPHERICAL NUCLEIC-ACIDS; CANCER-CELL CAPTURE; DRUG-DELIVERY; SIRNA
DELIVERY; POLYMERIC MICELLES; ULTRASENSITIVE DETECTION; ELECTROSPUN
NANOFIBERS; INSULIN DELIVERY; GENE-REGULATION; TUMOR-CELLS
AB Due to their size and tailorable physicochemical properties, nanomaterials are an emerging class of structures utilized in biomedical applications. There are now many prominent examples of nanomaterials being used to improve human health, in areas ranging from imaging and diagnostics to therapeutics and regenerative medicine. An overview of these examples reveals several common areas of synergy and future challenges. This Nano Focus discusses the current status and future potential of promising nanomaterials and their translation from the laboratory to the clinic, by highlighting a handful of successful examples.
C1 [Mitragotri, Samir] Univ Calif Santa Barbara, Dept Chem Engn, Ctr Bioengn, Santa Barbara, CA 93106 USA.
[Anderson, Daniel G.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA.
[Chen, Xiaoyuan] NIH, Natl Inst Biomed Imaging & Bioengn, Bethesda, MD 20892 USA.
[Chow, Edward K.] Natl Univ Singapore, Yong Loo Lin Sch Med, Canc Sci Inst Singapore, Singapore 119077, Singapore.
[Ho, Dean] UCLA, Sch Dent, Div Oral Biol & Med, Los Angeles, CA 90095 USA.
[Kabanov, Alexander V.] Univ N Carolina, Eshelman Sch Pharm, Div Mol Pharmaceut, Chapel Hill, NC 27599 USA.
[Kabanov, Alexander V.] Univ N Carolina, Eshelman Sch Pharm, Ctr Nanotechnol Drug Delivery, Chapel Hill, NC 27599 USA.
[Karp, Jeffrey M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Kataoka, Kazunori] Univ Tokyo, Dept Mat Engn, Tokyo 1138654, Japan.
[Kataoka, Kazunori] Univ Tokyo, Dept Bioengn, Tokyo 1138654, Japan.
[Mirkin, Chad A.; Petrosko, Sarah Hurst] Northwestern Univ, Dept Chem, Evanston, IL 60208 USA.
[Mirkin, Chad A.; Petrosko, Sarah Hurst] Northwestern Univ, Int Inst Nanotechnol, Evanston, IL 60208 USA.
[Shi, Jinjun] Harvard Univ, Sch Med, Brigham & Womens Hosp, Lab Nanoengn & Drug Delivery,Dept Anesthesiol, Boston, MA 02115 USA.
[Stevens, Molly M.] Univ London Imperial Coll Sci Technol & Med, Inst Biomed Engn, Dept Bioengn, Dept Mat, London SW7 2AZ, England.
[Sun, Shouheng] Brown Univ, Dept Chem, Providence, RI 02912 USA.
[Teoh, Sweehin; Xu, Chenjie] Nanyang Technol Univ, Sch Chem & Biomed Engn, Singapore 639798, Singapore.
[Venkatraman, Subbu S.] Nanyang Technol Univ, Sch Mat Sci & Engn, Singapore 639798, Singapore.
[Xia, Younan] Georgia Inst Technol, Wallace H Coulter Dept Biomed Engn, Atlanta, GA 30322 USA.
[Xia, Younan] Emory Univ, Atlanta, GA 30322 USA.
[Wang, Shutao] Chinese Acad Sci, Tech Inst Phys & Chem, Beijing 100190, Peoples R China.
[Gu, Zhen] Univ N Carolina, Joint Dept Biomed Engn, Raleigh, NC 27695 USA.
[Gu, Zhen] N Carolina State Univ, Raleigh, NC 27695 USA.
[Gu, Zhen] Univ N Carolina, Eshelman Sch Pharm, Div Mol Pharmaceut, Chapel Hill, NC 27599 USA.
[Gu, Zhen] Univ N Carolina, Eshelman Sch Pharm, Ctr Nanotechnol Drug Delivery, Chapel Hill, NC 27599 USA.
[Gu, Zhen] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC 27695 USA.
RP Mitragotri, S (reprint author), Univ Calif Santa Barbara, Dept Chem Engn, Ctr Bioengn, Santa Barbara, CA 93106 USA.
EM samir@engr.ucsb.edu; zgu@email.unc.edu; cjxu@ntu.edu.sg
RI Xia, Younan/E-8499-2011; Kataoka, Kazunori/K-7108-2012; Shutao,
Wang/E-5448-2011; Mirkin, Chad/E-3911-2010; Venkatraman,
Subramanian/A-2228-2011; xu, chenjie/E-4075-2012;
OI Kataoka, Kazunori/0000-0002-8591-413X; Shutao, Wang/0000-0002-2559-5181;
Venkatraman, Subramanian/0000-0002-8693-1070; Xu,
Chenjie/0000-0002-8278-3912
FU Intramural NIH HHS [Z99 EB999999, ZIA EB000073-06]
NR 86
TC 58
Z9 60
U1 57
U2 316
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1936-0851
EI 1936-086X
J9 ACS NANO
JI ACS Nano
PD JUL
PY 2015
VL 9
IS 7
BP 6644
EP 6654
DI 10.1021/acsnano.5b03569
PG 11
WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience &
Nanotechnology; Materials Science, Multidisciplinary
SC Chemistry; Science & Technology - Other Topics; Materials Science
GA CO0EP
UT WOS:000358823200002
PM 26115196
ER
PT J
AU Wang, Z
Wang, Y
Wang, ZY
Zhao, J
Gutkind, JS
Srivatsan, A
Zhang, GF
Liao, HS
Fu, X
Jin, A
Tong, X
Niu, G
Chen, XY
AF Wang, Zhe
Wang, Yu
Wang, Zhiyong
Zhao, Jun
Gutkind, J. Silvio
Srivatsan, Avinash
Zhang, Guofeng
Liao, Hsien-Shun
Fu, Xiao
Jin, Albert
Tong, Xiao
Niu, Gang
Chen, Xiaoyuan
TI Polymeric Nanovehicle Regulated Spatiotemporal Real-Time Imaging of the
Differentiation Dynamics of Transplanted Neural Stem Cells after
Traumatic Brain Injury
SO ACS NANO
LA English
DT Article
DE stem cells; imaging; traumatic brain injury; differentiation;
nanoparticles
ID DRUG-DELIVERY SYSTEM; SPINAL-CORD-INJURY; ANTICANCER ACTIVITIES; ADULT
BRAIN; NEUROGENESIS; NEURONS; NANOPARTICLES; MODEL; ANTIANGIOGENESIS;
NEUROPROTECTION
AB Recent advances in neural stem cell (NSC) transplantation have led to an inspiring progress in alleviating central nervous system (CNS) damages and restoring brain functions from diseases or injuries. One challenge of NSC transplantation is directed differentiation of transplanted NSCs into desired neuronal subtypes, such as neurons, to compensate the adverse impact of brain injury; another challenge lies in the lack of tools to noninvasively monitor the dynamics of NSC differentiation after transplantation in vivo. In this study, we developed a polymer nanovehicle for morphogen sustained release to overcome the drawbacks of conventional methods to realize the long-term directed NSC differentiation in vivo. Moreover, we constructed a bicistronic vector with a unique neuron specific gene tubb3 promoter to drive reporter gene expression for real-time imaging of NSC differentiation and migration. The developed uniform nanovehicle showed efficient NSC uptake and achieved a controlled release of morphogen in cytosol to consistently stimulate NSC differentiation into neurons at a sustainably effective concentration. The spatiotemporal imaging results showed a multiplexed migration, proliferation, differentiation, and apoptosis orchestra of transplanted NSCs regulated by nanovehicles in TBI mice. The imaging results also uncovered the peak time of NSC differentiation in vivo. Although we observed only a handful of NSCs ultimately migrated to the TBI area and differentiated into neurons, those neurons were functional, ameliorating the detrimental impact of TBI. The imaging findings enabled by the nanovehicle and the neuron specific bicistronic vector provide additional understanding of the in vivo behaviors of transplanted NSCs in neuronal regenerative medicine.
C1 [Wang, Zhe; Wang, Yu; Srivatsan, Avinash; Liao, Hsien-Shun; Fu, Xiao; Tong, Xiao; Niu, Gang; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
[Wang, Zhiyong; Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
[Zhao, Jun] NIMH, Unit Synapse Dev & Plast, NIH, Bethesda, MD 20892 USA.
[Zhang, Guofeng; Liao, Hsien-Shun; Fu, Xiao; Jin, Albert] Natl Inst Biomed Imaging & Bioengn, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA.
RP Chen, XY (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
EM shawn.chen@nih.gov
OI Jin, Albert/0000-0003-3826-1081
FU Center for Neuroscience and Regenerative Medicine (CNRM) program at the
Henry M. Jackson Foundation; Intramural Research Program (IRP) of the
National Institute of Biomedical Imaging and Bioengineering (NIBIB),
National Institutes of Health (NIH)
FX This study was supported, in part, by the Center for Neuroscience and
Regenerative Medicine (CNRM) program at the Henry M. Jackson Foundation
and the Intramural Research Program (IRP) of the National Institute of
Biomedical Imaging and Bioengineering (NIBIB), National Institutes of
Health (NIH).
NR 44
TC 8
Z9 8
U1 6
U2 39
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1936-0851
EI 1936-086X
J9 ACS NANO
JI ACS Nano
PD JUL
PY 2015
VL 9
IS 7
BP 6683
EP 6695
DI 10.1021/acsnano.5b00690
PG 13
WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience &
Nanotechnology; Materials Science, Multidisciplinary
SC Chemistry; Science & Technology - Other Topics; Materials Science
GA CO0EP
UT WOS:000358823200005
PM 26020550
ER
PT J
AU Bjelobaba, I
Janjic, MM
Kucka, M
Stojilkovic, SS
AF Bjelobaba, Ivana
Janjic, Marija M.
Kucka, Marek
Stojilkovic, Stanko S.
TI Cell Type-Specific Sexual Dimorphism in Rat Pituitary Gene Expression
During Maturation
SO BIOLOGY OF REPRODUCTION
LA English
DT Article
DE Cga; Fshb; Gh1; Gnrhr; Lhb; Pomc; Prl; Tshb
ID GONADOTROPIN-RELEASING-HORMONE; FOLLICLE-STIMULATING-HORMONE;
MESSENGER-RIBONUCLEIC-ACID; CYCLASE-ACTIVATING POLYPEPTIDE;
GROWTH-HORMONE; DIFFERENTIAL EXPRESSION; FEMALE RATS; TRANSCRIPTION
FACTORS; PUBERTAL DEVELOPMENT; GLAND DEVELOPMENT
AB The most obvious functional differences between mammalian males and females are related to the control of reproductive physiology and include patterns of GnRH and gonadotropin release, the timing of puberty, sexual and social behavior, and the regulation of food intake and body weight. Using the rat as the best-studied mammalian model for maturation, we examined the expression of major anterior pituitary genes in five secretory cell types of developing males and females. Corticotrophs show comparable Pomc profiles in both sexes, with the highest expression occurring during the infantile period. Somatotrophs and lactotrophs also exhibit no difference in Gh1 and Prl profiles during embryonic to juvenile age but show the amplification of Prl expression in females and Gh1 expression in males during peripubertal and postpubertal ages. Gonadotrophs exhibit highly synchronized Lhb, Fshb, Cga, and Gnrhr expression in both sexes, but the peak of expression occurs during the infantile period in females and at the end of the juvenile period in males. Thyrotrophs also show different developmental Tshb profiles, which are synchronized with the expression of gonadotroph genes in males but not in females. These results indicate the lack of influence of sex on Pomc expression and the presence of two patterns of sexual dimorphism in the expression of other pituitary genes: a time shift in the peak expression during postnatal development, most likely reflecting the perinatal sex-specific brain differentiation, and modulation of the amplitude of expression during late development, which is secondary to the establishment of the hypothalamic-pituitary-gonadal and -thyroid axes.
C1 [Bjelobaba, Ivana; Janjic, Marija M.; Kucka, Marek; Stojilkovic, Stanko S.] Eunice Kennedy Shiver Natl Inst Child Hlth & Huma, Sect Cellular Signaling, Program Dev Neurosci, NIH, Bethesda, MD USA.
RP Stojilkovic, SS (reprint author), NICHD, Bldg 49,Room 6A 36 49 Convent Dr, Bethesda, MD 20892 USA.
EM stojilks@mail.nih.gov
FU Intramural Research Program of the National Institute of Child Health
and Human Development [ZIA HD000195-20]
FX This work was supported by the Intramural Research Program of the
National Institute of Child Health and Human Development (ZIA
HD000195-20).
NR 57
TC 2
Z9 2
U1 3
U2 5
PU SOC STUDY REPRODUCTION
PI MADISON
PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA
SN 0006-3363
EI 1529-7268
J9 BIOL REPROD
JI Biol. Reprod.
PD JUL 1
PY 2015
VL 93
IS 1
AR 21
DI 10.1095/biolreprod.115.129320
PG 9
WC Reproductive Biology
SC Reproductive Biology
GA CO8SP
UT WOS:000359441800015
PM 26063874
ER
PT J
AU Vandevijvere, S
Chow, CC
Hall, KD
Umali, E
Swinburn, BA
AF Vandevijvere, Stefanie
Chow, Carson C.
Hall, Kevin D.
Umali, Elaine
Swinburn, Boyd A.
TI Increased food energy supply as a major driver of the obesity epidemic:
a global analysis
SO BULLETIN OF THE WORLD HEALTH ORGANIZATION
LA English
DT Article
ID NUTRITION TRANSITION; PHYSICAL-ACTIVITY; WEIGHT STATUS; ASSOCIATION;
PREVALENCE; POLICY; TIME; ROAD
AB Objective We investigated associations between changes in national food energy supply and in average population body weight.
Methods We collected data from 24 high-, 27 middle- and 18 low-income countries on the average measured body weight from global databases, national health and nutrition survey reports and peer-reviewed papers. Changes in average body weight were derived from study pairs that were at least four years apart (various years, 1971-2010). Selected study pairs were considered to be representative of an adolescent or adult population, at national or subnational scale. Food energy supply data were retrieved from the Food and Agriculture Organization of the United Nations food balance sheets. We estimated the population energy requirements at survey time points using Institute of Medicine equations. Finally, we estimated the change in energy intake that-could theoretically account for the observed change in average body weight using an experimentally-validated model.
Findings In 56 countries, an increase in food energy supply was associated with an increase in average body weight. In 45 countries, the increase in food energy supply was higher than the model-predicted increase in energy intake. The association between change in food energy supply and change in body weight was statistically significant overall and for high-income countries (P<0.001).
Conclusion The findings suggest that increases in food energy supply are sufficient to explain increases in average population body weight, especially in high-income countries. Policy efforts are needed to improve the healthiness of food systems and environments to reduce global obesity.
C1 [Vandevijvere, Stefanie; Umali, Elaine; Swinburn, Boyd A.] Univ Auckland, Sch Populat Hlth, Auckland 1, New Zealand.
[Chow, Carson C.; Hall, Kevin D.] NIH, Lab Biol Modeling, Bethesda, MD 20892 USA.
RP Vandevijvere, S (reprint author), Univ Auckland, Sch Populat Hlth, 261 Morrin Rd, Auckland 1, New Zealand.
EM s.vandevijvere@auckland.ac.nz
FU University of Auckland Vice Chancellor's strategic fund; NIH's National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), USA
FX Stefanie Vandevijvere and Boyd Swinburn are funded by the University of
Auckland Vice Chancellor's strategic fund. Carson Chow and Kevin Hall
are funded by the intramural research programme of the NIH's National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), USA.
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U2 22
PU WORLD HEALTH ORGANIZATION
PI GENEVA 27
PA MARKETING AND DISSEMINATION, CH-1211 GENEVA 27, SWITZERLAND
SN 0042-9686
EI 1564-0604
J9 B WORLD HEALTH ORGAN
JI Bull. World Health Organ.
PD JUL
PY 2015
VL 93
IS 7
BP 446
EP 456
DI 10.2471/BLT.14.150565
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CO1BO
UT WOS:000358888100011
PM 26170502
ER
PT J
AU Sanders, MG
Parsons, MJ
Howard, AGA
Liu, J
Fassio, SR
Martinez, JA
Bouchier-Hayes, L
AF Sanders, M. G.
Parsons, M. J.
Howard, A. G. A.
Liu, J.
Fassio, S. R.
Martinez, J. A.
Bouchier-Hayes, L.
TI Single-cell imaging of inflammatory caspase dimerization reveals
differential recruitment to inflammasomes
SO CELL DEATH & DISEASE
LA English
DT Article
ID MOLECULAR-CLONING; ASC; ACTIVATION; PROTEIN; APOPTOSIS; DOMAIN; IPAF;
INTERLEUKIN-1-BETA; SPECIFICITY; MEMBERS
AB The human inflammatory caspases, including caspase-1, -4, -5 and -12, are considered as key regulators of innate immunity protecting from sepsis and numerous inflammatory diseases. Caspase-1 is activated by proximity-induced dimerization following recruitment to inflammasomes but the roles of the remaining inflammatory caspases in inflammasome assembly are unclear. Here, we use caspase bimolecular fluorescence complementation to visualize the assembly of inflammasomes and dimerization of inflammatory caspases in single cells. We observed caspase-1 dimerization induced by the coexpression of a range of inflammasome proteins and by lipospolysaccharide (LPS) treatment in primary macrophages. Caspase-4 and -5 were only dimerized by select inflammasome proteins, whereas caspase-12 dimerization was not detected by any investigated treatment. Strikingly, we determined that certain inflammasome proteins could induce heterodimerization of caspase-1 with caspase-4 or -5. Caspase-5 homodimerization and caspase-1/-5 heterodimerization was also detected in LPS-primed primary macrophages in response to cholera toxin subunit B. The subcellular localization and organization of the inflammasome complexes varied markedly depending on the upstream trigger and on which caspase or combination of caspases were recruited. Three-dimensional imaging of the ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain)/caspase-1 complexes revealed a large spherical complex of ASC with caspase-1 dimerized on the outer surface. In contrast, NALP1 (NACHT leucine-rich repeat protein 1)/caspase-1 complexes formed large filamentous structures. These results argue that caspase-1, -4 or -5 can be recruited to inflammasomes under specific circumstances, often leading to distinctly organized and localized complexes that may impact the functions of these proteases.
C1 [Sanders, M. G.; Parsons, M. J.; Howard, A. G. A.; Liu, J.; Fassio, S. R.; Bouchier-Hayes, L.] Baylor Coll Med, Dept Pediat Hematol, Houston, TX 77030 USA.
[Sanders, M. G.; Parsons, M. J.; Howard, A. G. A.; Liu, J.; Fassio, S. R.; Bouchier-Hayes, L.] Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA.
[Sanders, M. G.; Liu, J.] Rice Univ, Dept Biochem & Cell Biol, Houston, TX 77251 USA.
[Martinez, J. A.] NIEHS, Dept Immun Inflammat & Dis, Res Triangle Pk, NC 27709 USA.
[Bouchier-Hayes, L.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
RP Bouchier-Hayes, L (reprint author), Baylor Coll Med, Dept Pediat Hematol, 1102 Bates Ave,FC 1770-18, Houston, TX 77030 USA.
EM lxbouchi@txch.org
FU BCM SMART program; Texas Children's Hospital Pediatrics Pilot award
FX We gratefully acknowledge Rice University for the support and mentorship
of MGS and JL, specifically Dereth Phillips and the Bioc310 program.
AGAH was supported by the BCM SMART program. We thank Jonathan Flanagan
for critical reading of the manuscript. This work was supported in part
by a Texas Children's Hospital Pediatrics Pilot award to LBH.
NR 31
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PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-4889
J9 CELL DEATH DIS
JI Cell Death Dis.
PD JUL
PY 2015
VL 6
AR e1813
DI 10.1038/cddis.2015.186
PG 11
WC Cell Biology
SC Cell Biology
GA CN9SH
UT WOS:000358788800013
PM 26158519
ER
PT J
AU Rho, J
Ho, N
Prasad, V
AF Rho, Jason
Ho, Nancy
Prasad, Vinay
TI Roflumilast in COPD Response
SO CHEST
LA English
DT Letter
C1 [Rho, Jason] Univ Texas SW Med Ctr Dallas, Dept Med, Div Pulmonol & Crit Care, Dallas, TX 75390 USA.
[Ho, Nancy] Natl Inst Diabet & Digest & Kidney Dis, Bethesda, MD USA.
[Prasad, Vinay] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Prasad, V (reprint author), NCI, Med Oncol Branch, NIH, 10 Ctr Dr,10-12N226, Bethesda, MD 20892 USA.
EM vinayak.prasad@nih.gov
NR 5
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U1 0
U2 1
PU AMER COLL CHEST PHYSICIANS
PI GLENVIEW
PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA
SN 0012-3692
J9 CHEST
JI Chest
PD JUL
PY 2015
VL 148
IS 1
BP E31
EP E32
DI 10.1378/chest.15-0837
PG 2
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA CO2QZ
UT WOS:000359003000012
PM 26149564
ER
PT J
AU Wardyn, SE
Forshey, BM
Farina, SA
Kates, AE
Nair, R
Quick, MK
Wu, JY
Hanson, BM
O'Malley, SM
Shows, HW
Heywood, EM
Beane-Freeman, LE
Lynch, CF
Carrel, M
Smith, TC
AF Wardyn, Shylo E.
Forshey, Brett M.
Farina, Sarah A.
Kates, Ashley E.
Nair, Rajeshwari
Quick, Megan K.
Wu, James Y.
Hanson, Blake M.
O'Malley, Sean M.
Shows, Hannah W.
Heywood, Ellen M.
Beane-Freeman, Laura E.
Lynch, Charles F.
Carrel, Margaret
Smith, Tara C.
TI Swine Farming Is a Risk Factor for Infection With and High Prevalence of
Carriage of Multidrug-Resistant Staphylococcus aureus
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
DE Staphylococcus aureus; multidrug resistance; swine; colonization;
livestock-associated Staphylococcus aureus
ID NASAL COLONIZATION; UNITED-STATES; PIG FARMERS; MRSA CC398; HEALTH;
EPIDEMIOLOGY; ST398; USA
AB Background. Livestock-associated Staphylococcus aureus (LA-SA) has been documented worldwide. However, much remains unknown about LA-SA colonization and infection, especially in rural environments.
Methods. We conducted a large-scale prospective study of 1342 Iowans, including individuals with livestock contact and a community-based comparison group. Nasal and throat swabs were collected to determine colonization at enrollment, and skin infection swabs over 17 months were assessed for S. aureus. Outcomes included carriage of S. aureus, methicillin-resistant S. aureus (MRSA), tetracycline-resistant S. aureus (TRSA), multidrug-resistant S. aureus (MDRSA), and LA-SA.
Results. Of 1342 participants, 351 (26.2%; 95% confidence interval [CI], 23.8%-28.6%) carried S. aureus. MRSA was isolated from 34 (2.5%; 95% CI, 1.8%-3.5%) and LA-SA from 131 (9.8%; 95% CI, 8.3%-11.5%) of the 1342 participants. Individuals with current swine exposure were significantly more likely to carry S. aureus (prevalence ratio [PR], 1.8; 95% CI, 1.4-2.2), TRSA (PR, 8.4; 95% CI, 5.6-12.6), MDRSA (PR, 6.1; 95% CI, 3.8-10.0), and LA-SA (PR, 5.8; 95% CI, 3.9-8.4) than those lacking exposure. Skin infections (n = 103) were reported from 67 individuals, yielding an incidence rate of 6.6 (95% CI, 4.9-8.9) per 1000 person-months.
Conclusions. Current swine workers are 6 times more likely to carry MDRSA than those without current swine exposure. We observed active infections caused by LA-SA. This finding suggests that individuals with livestock contact may have a high prevalence of exposure to, and potentially infection with, antibiotic-resistant S. aureus strains, including LA-SA strains.
C1 [Wardyn, Shylo E.; Forshey, Brett M.; Farina, Sarah A.; Kates, Ashley E.; Nair, Rajeshwari; Quick, Megan K.; Wu, James Y.; Hanson, Blake M.; O'Malley, Sean M.; Shows, Hannah W.] Univ Iowa, Ctr Emerging Infect Dis, Iowa City, IA 52242 USA.
[Wardyn, Shylo E.; Forshey, Brett M.; Kates, Ashley E.; Nair, Rajeshwari; Wu, James Y.; Hanson, Blake M.] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA.
[Carrel, Margaret] Univ Iowa, Coll Liberal Arts & Sci, Dept Geog & Sustainabil Sci, Iowa City, IA USA.
[Heywood, Ellen M.] Univ Iowa, Coll Publ Hlth, Dept Occupat & Environm Hlth, Iowa City, IA USA.
[Beane-Freeman, Laura E.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Smith, Tara C.] Kent State Univ, Coll Publ Hlth, Dept Biostat Environm Hlth Sci & Epidemiol, Kent, OH 44240 USA.
RP Smith, TC (reprint author), 750 Hilltop Dr,Lowry Hall, Kent, OH 44242 USA.
EM tsmit176@kent.edu
RI Beane Freeman, Laura/C-4468-2015
OI Beane Freeman, Laura/0000-0003-1294-4124
FU National Cancer Institute, National Institutes of Health [Z01-CP010119];
Agency for Healthcare Research and Quality [R18 HS019966]
FX This work was supported in part by the intramural research program of
the National Cancer Institute, National Institutes of Health
(Z01-CP010119), and by the Agency for Healthcare Research and Quality
(R18 HS019966).
NR 35
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U1 4
U2 34
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 JUL 1
PY 2015
VL 61
IS 1
BP 59
EP 66
DI 10.1093/cid/civ234
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA CO7EX
UT WOS:000359323500011
PM 25931444
ER
PT J
AU Bornstein, MH
Putnick, DL
Bradley, RH
Lansford, JE
Deater-Deckard, K
AF Bornstein, Marc H.
Putnick, Diane L.
Bradley, Robert H.
Lansford, Jennifer E.
Deater-Deckard, Kirby
TI Pathways among Caregiver Education, Household Resources, and Infant
Growth in 39 Low- and Middle-Income Countries
SO INFANCY
LA English
DT Article
ID CHILDS NUTRITIONAL-STATUS; MOTHERS EDUCATION; HOUSING QUALITY; FIT
INDEXES; HEALTH; UNDERNUTRITION; DIARRHEA; ACCESS; WATER
AB Caregiver education is known to relate to the growth of children, but possible mediation mechanisms of this association are poorly characterized and generally lack empirical support. We test whether instructional capital (caregiver education) leads to improved infant growth through availability of physical capital (household resources) across a wide swath of low- and middle-income countries (LMIC). Using the Multiple Indicator Cluster Survey, we explore relations among caregiver education, household resources, and infant (M age = 0.99 years) growth in 117,881 families living in 39 LMIC. Overall, household resources mediated 76% of the small association between caregiver education and infant growth. When disaggregated by countries characterized by low, medium, and high levels of human development (as indexed by average life expectancy, education, and gross domestic product), household resources mediated 48-78% of the association between caregiver education and infant growth. Caregiver education had effects on infant growth through household resources in countries characterized by low, medium, and high levels of human development; for girls and boys; and controlling for indexes of infant feeding and health.
C1 [Bornstein, Marc H.; Putnick, Diane L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Child & Family Res, NIH, US PHS, Bethesda, MD 20892 USA.
[Bradley, Robert H.] Arizona State Univ, Tempe, AZ 85287 USA.
[Lansford, Jennifer E.] Duke Univ, Durham, NC 27706 USA.
[Deater-Deckard, Kirby] Virginia Polytech Inst & State Univ, Blacksburg, VA 24061 USA.
RP Bornstein, MH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Child & Family Res, Suite 8030 6705 Rockledge Dr, Bethesda, MD 20892 USA.
EM Marc_H_Bornstein@nih.gov
OI Putnick, Diane/0000-0002-6323-749X
FU Intramural Program of the NIH, NICHD
FX MHB and DLP were supported by the Intramural Program of the NIH, NICHD.
The study sponsor had no role in study design, data collection, data
analysis, data interpretation, or writing of the report. We thank B.
Gates for stimulating this inquiry and UNICEF and individual countries
for collecting the data.
NR 56
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U1 2
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1525-0008
EI 1532-7078
J9 INFANCY
JI Infancy
PD JUL-AUG
PY 2015
VL 20
IS 4
BP 353
EP 376
DI 10.1111/infa.12086
PG 24
WC Psychology, Developmental
SC Psychology
GA CO0QX
UT WOS:000358858200001
PM 26273231
ER
PT J
AU Saeedipour, S
Tai, D
Fane, JW
AF Saeedipour, Sirus
Tai, David
Fang, Jianwen
TI ChemCom: A Software Program for Searching and Comparing Chemical
Libraries
SO JOURNAL OF CHEMICAL INFORMATION AND MODELING
LA English
DT Article
ID FINGERPRINTS; ALGORITHMS
AB An efficient chemical comparator, a computer application facilitating searching and comparing chemical libraries, is useful in drug discovery and other relevant areas. The need for an efficient and user-friendly chemical comparator prompted us to develop ChemCom (Chemical Comparator) based on Java Web Start (JavaWS) technology. ChemCom,provides a user-friendly graphical interface to a: number of fast algorithms including a novel algorithm termed UnionBit Tree Algorithm. It utilizes an intuitive stepwise mechanism for selecting chemical comparison parameters before starting the comparison process, UnionBit has shown approximately an 165% Speedup on average compared to its closest competitive algorithm implemented in ChemCom over real data It is approximately 11 times faster than the Open Babel FastSearch algorithm in our tests. ChemCom can be accessed free-of-charge via a user-friendly website at http://bioinformatics.org/chemcom/.
C1 [Fang, Jianwen] NCI, Biometr Res Branch, Div Canc Treatment & Diag, Rockville, MD 20850 USA.
[Saeedipour, Sirus; Tai, David; Fang, Jianwen] Univ Kansas, Appl Bioinformat Lab, Lawrence, KS 66047 USA.
RP Fane, JW (reprint author), NCI, Biometr Res Branch, Div Canc Treatment & Diag, 9609 Med Ctr Dr, Rockville, MD 20850 USA.
EM jianwen.fang@nih.gov
NR 10
TC 0
Z9 0
U1 2
U2 4
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1549-9596
EI 1549-960X
J9 J CHEM INF MODEL
JI J. Chem Inf. Model.
PD JUL
PY 2015
VL 55
IS 7
BP 1292
EP 1296
DI 10.1021/ci500713s
PG 5
WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Computer Science,
Information Systems; Computer Science, Interdisciplinary Applications
SC Pharmacology & Pharmacy; Chemistry; Computer Science
GA CO0DW
UT WOS:000358821300002
PM 26067384
ER
PT J
AU Tarasova, OA
Urusova, AF
Filimonov, DA
Nicklaus, MC
Zakharov, AV
Poroikov, VV
AF Tarasova, Olga A.
Urusova, Aleksandra F.
Filimonov, Dmitry A.
Nicklaus, Marc C.
Zakharov, Alexey V.
Poroikov, Vladimir V.
TI QSAR Modeling Using Large-Scale Databases: Case Study for HIV-1 Reverse
Transcriptase Inhibitors
SO JOURNAL OF CHEMICAL INFORMATION AND MODELING
LA English
DT Article
ID THERAPEUTIC TARGET DATABASE; HUMAN METABOLOME DATABASE; NONNUCLEOSIDE
INHIBITORS; CHEMICAL-STRUCTURE; DIPYRIDODIAZEPINONES; IDENTIFICATION;
INFORMATION; RESOURCES; DRUGBANK; CHEMBL
AB Large-scale databases are important sources of training sets for various QSAR modeling approaches. Generally, these databases contain information extracted from different sources. This variety of sources' can produce inconsistency in-the data, defined as sometimes widely diverging activity results for the same Compound against the same: target. Because such inconsistency can reduce the accuracy of predictive Models built from these data, we are addressing the question of how best to use data from publicly and commercially accessible databases to create accurate and predictive QSAR models. We investigate the suitability of commercially and publicly available databases to QSAR modeling Of antiviral activity (HIV-1 reverse transcriptase (RT) inhibition). We present several methods for the creation of modeling (i.e., training and test) sets from two, either commercially or,freely available, databases: Thomson Reuters. Integrity and ChEMBL. We found that the typical predictivities of QSAR models obtained using these different modeling set compilation methods differ significantly from each other.. The best results were obtained using training sets compiled for compounds tested using only one method and material (i.e., a specific type of biological assay). Compound sets aggregated by target only typically yielded poorly predictive models: We discuss the possibility of "mix-and-matching" assay data across aggregating databases such as ChEMBL and Integrity and their current severe limitations for this purpose. One of them is the general lack of complete and semantic/computer-parsable descriptions of assay methodology carried by these databases that would allow one to determine mix-and-matchability of-result sets at the assay level.
C1 [Tarasova, Olga A.; Urusova, Aleksandra F.; Filimonov, Dmitry A.; Poroikov, Vladimir V.] Inst Biochem Chem, Moscow 119121, Russia.
[Nicklaus, Marc C.; Zakharov, Alexey V.] NCI, CADD Grp, Biol Chem Lab, Ctr Canc Res,Natl Inst Hlth,DHHS,NCI Frederick, Frederick, MD 21702 USA.
RP Tarasova, OA (reprint author), Inst Biochem Chem, 10-8,Pogodinskaya St, Moscow 119121, Russia.
EM olga.a.tarasova@gmail.com
RI Tarasova, Olga/E-4318-2014; Tarasova, Olga/F-1248-2017
OI Tarasova, Olga/0000-0002-4230-3849; Nicklaus, Marc/0000-0002-4775-7030;
Tarasova, Olga/0000-0002-3723-7832
FU Russian Foundation of Basic Research [13-04-91455_NIH-a]; Intramural
Program of the U.S. National Institutes of Health
FX This work was supported by the Russian Foundation of Basic Research
(grant No. 13-04-91455_NIH-a). Part of this work was supported by the
Intramural Program of the U.S. National Institutes of Health. The
content of this publication does not necessarily reflect the views or
policies of the U.S. Department of Health and Human Services, nor does
mention of trade names, commercial products, or organizations imply
endorsement by the U.S. Government.
NR 31
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U1 2
U2 12
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1549-9596
EI 1549-960X
J9 J CHEM INF MODEL
JI J. Chem Inf. Model.
PD JUL
PY 2015
VL 55
IS 7
BP 1388
EP 1399
DI 10.1021/acs.jcim.5b00019
PG 12
WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Computer Science,
Information Systems; Computer Science, Interdisciplinary Applications
SC Pharmacology & Pharmacy; Chemistry; Computer Science
GA CO0DW
UT WOS:000358821300012
PM 26046311
ER
PT J
AU Byrareddy, S
Arthos, J
Cicala, C
Reimann, K
Parslow, T
Santangelo, P
Villinger, F
Fauci, A
Ansari, A
AF Byrareddy, Siddappa
Arthos, James
Cicala, Claudia
Reimann, Keith
Parslow, Tristram
Santangelo, Philip
Villinger, Francois
Fauci, Anthony
Ansari, Aftab
TI Treatment with anti-alpha 4 beta 7 integrin antibody reduces
virus-mediated gastrointestinal pathology by targeting distinct mucosal
tissues
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Meeting Abstract
C1 [Byrareddy, Siddappa; Parslow, Tristram; Villinger, Francois; Ansari, Aftab] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA.
[Arthos, James; Cicala, Claudia; Fauci, Anthony] Natl Inst Allergy & Infect Dis, Immunoregulat Lab, NIH, Bethesda, MD USA.
[Reimann, Keith] Univ Massachusetts, Sch Med, Dept Mass Biol, Boston, MA 02125 USA.
[Santangelo, Philip] Georgia Inst Technol, Wallace H Coulter Dept Biomed Engn, Atlanta, GA 30332 USA.
[Santangelo, Philip] Emory Univ, Atlanta, GA 30322 USA.
EM siddappa.n.byrareddy@emory.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD JUL
PY 2015
VL 18
SU 4
MA MOAA0202
DI 10.7448/IAS.18.5.20324
PG 2
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA CN8FS
UT WOS:000358675700008
ER
PT J
AU Capoferri, A
Sievers, M
Redd, A
Cash, A
Xu, D
Porcella, SF
Quinn, T
Siliciano, RF
Levis, M
Ambinder, RF
Durand, CM
AF Capoferri, Adam
Sievers, Matthew
Redd, Andrew
Cash, Ayla
Xu, Daniel
Porcella, Steven F.
Quinn, Thomas
Siliciano, Robert F.
Levis, Mark
Ambinder, Richard F.
Durand, Christine M.
TI HIV rebound and meningoencephalitis following ART interruption after
allogeneic hematopoietic stem cell transplant: an investigation of the
source of HIV rebound
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Meeting Abstract
C1 Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA.
[Capoferri, Adam; Sievers, Matthew; Redd, Andrew; Cash, Ayla; Xu, Daniel; Quinn, Thomas; Siliciano, Robert F.; Levis, Mark; Ambinder, Richard F.; Durand, Christine M.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA.
[Redd, Andrew; Porcella, Steven F.; Quinn, Thomas] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Porcella, Steven F.] Rocky Mt Labs, Genom Unit, Res Technol Branch, Hamilton, MT USA.
[Levis, Mark; Ambinder, Richard F.; Durand, Christine M.] Sidney Kimmel Canc Ctr, Baltimore, MD USA.
EM alongwi2@jhmi.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD JUL
PY 2015
VL 18
SU 4
MA MOPDA0105
DI 10.7448/IAS.18.5.20424
PG 2
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA CN8FS
UT WOS:000358675700141
ER
PT J
AU Chang, C
Cameron, P
Elliott, J
Perelson, A
Roche, M
Dantanarayana, A
Solomon, A
Naranbhai, V
Tenakoon, S
Hoh, R
McMahon, J
Sikaris, K
Hartogensis, W
Bacchetti, P
Hecht, F
Lifson, J
Deeks, S
Lewin, S
AF Chang, Christina
Cameron, Paul
Elliott, Julian
Perelson, Alan
Roche, Michael
Dantanarayana, Ashanti
Solomon, Ajantha
Naranbhai, Vivek
Tenakoon, Surekha
Hoh, Rebecca
McMahon, James
Sikaris, Ken
Hartogensis, Wendy
Bacchetti, Peter
Hecht, Frederick
Lifson, Jeffrey
Deeks, Steve
Lewin, Sharon
TI Time-associated changes in cell-associated HIV RNA in HIV-infected
subjects on suppressive antiretroviral therapy - implications for
clinical trials of cure interventions
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Meeting Abstract
C1 [Chang, Christina; Cameron, Paul; Roche, Michael; Dantanarayana, Ashanti; Solomon, Ajantha; Tenakoon, Surekha; Lewin, Sharon] Univ Melbourne, Doherty Inst, Melbourne, Vic, Australia.
[Chang, Christina; Cameron, Paul; Elliott, Julian; McMahon, James; Lewin, Sharon] Alfred Hosp, Dept Infect Dis, Melbourne, Vic, Australia.
[Perelson, Alan] Los Alamos Natl Lab, Los Alamos, NM USA.
[Naranbhai, Vivek] Univ Oxford, Dept Med, Oxford, England.
[Hoh, Rebecca; Deeks, Steve] Univ Calif San Francisco, Sch Med, San Francisco, CA USA.
[Sikaris, Ken] Dept Pathol, Melbourne, Vic, Australia.
[Hartogensis, Wendy; Bacchetti, Peter] Univ Calif San Francisco, Div Biostat, San Francisco, CA 94143 USA.
[Hecht, Frederick] Univ Calif San Francisco, Ctr Integrat Med, San Francisco, CA 94143 USA.
[Lifson, Jeffrey] NCI, Natl Lab Canc Res, Frederick, MD 21701 USA.
EM christina.chang@unimelb.edu.au
NR 0
TC 0
Z9 0
U1 0
U2 8
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD JUL
PY 2015
VL 18
SU 4
MA MOAA0106LB
DI 10.7448/IAS.18.5.20567
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA CN8FS
UT WOS:000358675700007
ER
PT J
AU Chang, L
Grabowski, MK
Ssekubugu, R
Nalugoda, F
Reynolds, S
Lessler, J
Moore, S
Quinn, T
Gray, R
Serwadda, D
Wawer, M
AF Chang, Larry
Grabowski, Mary K.
Ssekubugu, Robert
Nalugoda, Fred
Reynolds, Steven
Lessler, Justin
Moore, Sean
Quinn, Thomas
Gray, Ronald
Serwadda, David
Wawer, Maria
TI Heterogeneity of the HIV epidemic in rural Africa: findings from a
geospatially informed study of HIV epidemiology in fishing, trading, and
agrarian communities in Rakai, Uganda
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Meeting Abstract
C1 [Chang, Larry; Quinn, Thomas] Johns Hopkins Sch Med, Div Infect Dis, Baltimore, MD USA.
[Chang, Larry; Grabowski, Mary K.; Lessler, Justin; Moore, Sean; Gray, Ronald; Wawer, Maria] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Infect Dis Epidemiol, Baltimore, MD USA.
[Ssekubugu, Robert; Nalugoda, Fred; Serwadda, David] Rakai Hlth Sci Program, Kalisizo, Uganda.
[Reynolds, Steven; Quinn, Thomas] NIAID, Immunoregulat Lab, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
EM mgrabows@jhsph.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD JUL
PY 2015
VL 18
SU 4
MA WEPDC0105
DI 10.7448/IAS.18.5.20474
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA CN8FS
UT WOS:000358675700195
ER
PT J
AU Cohen, M
Chen, Y
McCauley, M
Gamble, T
Hosseinipour, M
Kumarasamy, N
Hakim, J
Kumwenda, N
Brum, T
Grinsztejn, B
Godbole, S
Chariyalertsak, S
Santos, BR
Mayer, K
Hoffman, I
Eshleman, S
Piwowar-Manning, E
Ou, SS
Cottle, L
Makhema, J
Mills, L
Panchia, R
Badal-Faesen, S
Eron, J
Gallant, J
Havlir, D
Swindells, S
Elharrar, V
Burns, D
Taha, T
Nielsen, K
Celentano, D
Essex, M
Fleming, T
AF Cohen, Myron
Chen, Ying
McCauley, Marybeth
Gamble, Theresa
Hosseinipour, Mina
Kumarasamy, Nagalingeshwaran
Hakim, James
Kumwenda, Newton
Brum, Tania
Grinsztejn, Beatriz
Godbole, Sheela
Chariyalertsak, Suwat
Santos, Breno Riegel
Mayer, Kenneth
Hoffman, Irving
Eshleman, Susan
Piwowar-Manning, Estelle
Ou, San-San
Cottle, Leslie
Makhema, Joseph
Mills, Lisa
Panchia, Ravindre
Badal-Faesen, Sharlaa
Eron, Joseph
Gallant, Joel
Havlir, Diane
Swindells, Susan
Elharrar, Vanessa
Burns, David
Taha, Taha
Nielsen, Karin
Celentano, David
Essex, Max
Fleming, Thomas
CA HPTN 052 Study Grp
TI Final results of the HPTN 052 randomized controlled trial:
antiretroviral therapy prevents HIV transmission
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Meeting Abstract
C1 [Cohen, Myron] Univ N Carolina, Dept Med, Div Infect Dis, Chapel Hill, NC USA.
[Chen, Ying; Cottle, Leslie] Fred Hutchinson Canc Res Ctr, Stat Ctr HIV AIDS Res & Prevent, Seattle, WA 98104 USA.
[McCauley, Marybeth; Gamble, Theresa] HIV Prevent Trials Network, HPTN, Washington, DC USA.
[Hosseinipour, Mina; Eron, Joseph] Univ N Carolina, Inst Global Hlth & Infect Dis, Chapel Hill, NC USA.
[Hosseinipour, Mina] Inst Global Hlth & Infect Dis, UNC Project Malawi, Lilongwe, Malawi.
[Kumarasamy, Nagalingeshwaran] YR Gaitonade Ctr AIDS Res & Educ, Chennai, Tamil Nadu, India.
[Hakim, James] Univ Zimbabwe, Harare, Zimbabwe.
[Kumwenda, Newton] Coll Med, Johns Hopkins Project, Blantyre, Malawi.
[Brum, Tania] Hosp Geral Nova Iguacu, Lab AIDS & Imunol Mol IOC Fiocruz, Rio De Janeiro, Brazil.
[Grinsztejn, Beatriz] Inst Nacl Infectol Evandro Chagas INI Fiocruz, Rio De Janeiro, Brazil.
[Godbole, Sheela] Natl AIDS Res Inst ICMR, Pune, Maharashtra, India.
[Chariyalertsak, Suwat] Chiang Mai Univ, Res Inst Hlth Sci, Chiang Mai 50000, Thailand.
[Santos, Breno Riegel] Hosp Nossa Senhora Conceicao, Porto Alegre, RS, Brazil.
[Mayer, Kenneth] Fenway Inst, Boston, MA USA.
[Mayer, Kenneth] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA.
[Hoffman, Irving] Univ N Carolina, Inst Global Hlth & Infect Dis, Chapel Hill, NC USA.
[Eshleman, Susan; Piwowar-Manning, Estelle] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Ou, San-San] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Makhema, Joseph] Botswana Harvard Aids Inst, Gaborone, Botswana.
[Mills, Lisa] KEMRI Ctr Dis Control & Prevent, Kisumu, Kenya.
[Panchia, Ravindre] Soweto HPTN CRS, Chris Hani Baragwanath Hosp, Soweto, South Africa.
[Badal-Faesen, Sharlaa] Univ Witwatersrand, Clin HIV Res Unit, Johannesburg, South Africa.
[Gallant, Joel] Southwest CARE Ctr, Albuquerque, NM USA.
[Havlir, Diane] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Swindells, Susan] Univ Nebraska, Med Ctr, Omaha, NE USA.
[Elharrar, Vanessa] NIAID, Clin Prevent Res Branch, Prevent Sci Program, Div Aids,NIH, Bethesda, MD 20892 USA.
[Taha, Taha] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Nielsen, Karin] David Geffen UCLA Sch Med, Los Angeles, CA USA.
[Celentano, David] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Essex, Max] Harvard TH Chan Sch Publ Hlth AIDS Initiat, Boston, MA USA.
[Essex, Max] Botswana Harvard AIDS Inst Partnership, Gaborone, Botswana.
[Fleming, Thomas] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
NR 0
TC 0
Z9 0
U1 1
U2 6
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD JUL
PY 2015
VL 18
SU 4
MA MOAC0101LB
DI 10.7448/IAS.18.5.20482
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA CN8FS
UT WOS:000358675700025
ER
PT J
AU Eshleman, SH
Hudelson, SE
Ou, SS
Redd, AD
Swanstrom, R
Porcella, SF
Chen, YQ
Piwowar-Manning, E
McCauley, M
Gamble, T
Sievers, M
Martens, CA
Bruno, D
Ping, LH
Dukhovlinova, E
Quinn, TC
Kumwenda, J
Maliwichi, M
Nhando, N
Akelo, V
Moyo, S
Panchia, R
Kumarasamy, N
Chotirosniramit, N
Rocha, MM
Bustorff, F
Grinsztejn, B
Mayer, KH
Hughes, JP
Cohen, MS
AF Eshleman, Susan H.
Hudelson, Sarah E.
Ou, San San
Redd, Andrew D.
Swanstrom, Ronald
Porcella, Stephen F.
Chen, Ying Q.
Piwowar-Manning, Estelle
McCauley, Marybeth
Gamble, Theresa
Sievers, Matthew
Martens, Craig A.
Bruno, Daniel
Ping, Li-Hua
Dukhovlinova, Elena
Quinn, Thomas C.
Kumwenda, Johnstone
Maliwichi, Madalitso
Nhando, Nehemiah
Akelo, Victor
Moyo, Sikhulile
Panchia, Ravindre
Kumarasamy, Nagalingeshwaran
Chotirosniramit, Nuntisa
Rocha, Marineide M.
Bustorff, Flavio
Grinsztejn, Beatriz
Mayer, Kenneth H.
Hughes, James P.
Cohen, Myron S.
CA HPTN 052 Study Team
TI Treatment as prevention: characterization of partner infections in the
HIV Prevention Trials Network 052 trial
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Meeting Abstract
C1 [Eshleman, Susan H.; Hudelson, Sarah E.; Piwowar-Manning, Estelle] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Ou, San San; Chen, Ying Q.; Hughes, James P.] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA.
[Redd, Andrew D.; Sievers, Matthew; Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Redd, Andrew D.; Quinn, Thomas C.] NIAID, Immunoregulat Lab, NIH, Baltimore, MD USA.
[Swanstrom, Ronald] Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC USA.
[Porcella, Stephen F.; Martens, Craig A.; Bruno, Daniel] NIAID, Genom Unit, Res Technol Sect, Rocky Mt Labs,Div Intramural Res,NIH, Hamilton, MT USA.
[McCauley, Marybeth] FHI 360, Washington, DC USA.
[Gamble, Theresa] FHI 360, Durham, NC USA.
[Ping, Li-Hua; Dukhovlinova, Elena] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Kumwenda, Johnstone] Coll Med, Johns Hopkins Project, Blantyre, Malawi.
[Maliwichi, Madalitso] UNC Project, Lilongwe, Malawi.
[Nhando, Nehemiah] Univ Zimbabwe, Harare, Zimbabwe.
[Akelo, Victor] KEMRI CDC, Kisumu, Kenya.
[Moyo, Sikhulile] Botswana Harvard AIDS Inst, Gaborone, Botswana.
[Panchia, Ravindre] Chris Hani Baragwanath Hosp, Soweto HPTN CRS, Soweto, South Africa.
[Kumarasamy, Nagalingeshwaran] YR Gaitonade Ctr AIDS Res & Educ, Madras, Tamil Nadu, India.
[Chotirosniramit, Nuntisa] Chiang Mai Univ, Res Inst Hlth Sci, Chiang Mai 50000, Thailand.
[Rocha, Marineide M.] Hosp Nossa Senhora Conceicao, Porto Alegre, RS, Brazil.
[Bustorff, Flavio] Hosp Geral de Nova Iguacu, Lab AIDS & Imunol Mol IOC Fiocruz, Rio De Janeiro, Brazil.
[Grinsztejn, Beatriz] Fiocruz MS, Inst Nacl Infectol Evandro Chagas INI Fiocruz, BR-21045900 Rio De Janeiro, Brazil.
[Mayer, Kenneth H.] Fenway Inst, Boston, MA USA.
[Mayer, Kenneth H.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA.
[Cohen, Myron S.] Univ N Carolina, Dept Med, Chapel Hill, NC USA.
NR 0
TC 0
Z9 0
U1 1
U2 6
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD JUL
PY 2015
VL 18
SU 4
MA MOAC0106LB
DI 10.7448/IAS.18.5.20484
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA CN8FS
UT WOS:000358675700030
ER
PT J
AU Holtz, TH
Chitwarakorn, A
Curlin, ME
Hughes, J
Amico, KR
Hendrix, C
Dye, BJ
Anderson, PL
Ou, SS
Elharrar, V
Eshleman, SH
Stirratt, M
Grant, RM
AF Holtz, Timothy H.
Chitwarakorn, Anupong
Curlin, Marcel E.
Hughes, James
Amico, K. Rivet
Hendrix, Craig
Dye, Bonnie J.
Anderson, Peter L.
Ou, San-San
Elharrar, Vanessa
Eshleman, Susan H.
Stirratt, Michael
Grant, Robert M.
CA Bangkok HPTN 067 ADAPT Study
TI HPTN 067/ADAPT study: a comparison of daily and non-daily pre-exposure
prophylaxis dosing in Thai men who have sex with men, Bangkok, Thailand
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Meeting Abstract
C1 [Holtz, Timothy H.; Curlin, Marcel E.] US Ctr Dis Control & Prevent Collaborat, Thailand Minist Publ Hlth, HIV STD Res Program, Bangkok, Thailand.
[Holtz, Timothy H.; Curlin, Marcel E.] Ctr Dis Control & Prevent, US Div HIV AIDS Prevent, Atlanta, GA USA.
[Chitwarakorn, Anupong] Minist Publ Hlth, Dept Dis Control, Nonthaburi, Thailand.
[Hughes, James] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Hughes, James; Ou, San-San] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Amico, K. Rivet] Univ Michigan, Dept Hlth Behav & Hlth Educ, Ann Arbor, MI 48109 USA.
[Hendrix, Craig] Johns Hopkins Univ, Dept Med, Baltimore, MD USA.
[Dye, Bonnie J.] FHI 360, Durham, NC USA.
[Anderson, Peter L.] Univ Colorado, Dept Pharmaceut Sci, Aurora, CO USA.
[Elharrar, Vanessa] NIAID, Clin Prevent Res Branch, PSP, DAIDS,NIH, Bethesda, MD 20892 USA.
[Eshleman, Susan H.] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA.
[Stirratt, Michael] NIMH, Div AIDS Res, Bethesda, MD 20892 USA.
[Grant, Robert M.] Univ Calif San Francisco, Gladstone Inst, San Francisco, CA 94143 USA.
EM tkh3@cdc.gov
RI Hendrix, Craig/G-4182-2014
OI Hendrix, Craig/0000-0002-5696-8665
NR 0
TC 0
Z9 0
U1 0
U2 7
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD JUL
PY 2015
VL 18
SU 4
MA MOAC0306LB
DI 10.7448/IAS.18.5.20539
PG 2
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA CN8FS
UT WOS:000358675700041
ER
PT J
AU Hosek, S
Rudy, B
Landovitz, R
Kapogiannis, B
Siberry, G
Liu, N
Rutledge, B
Brothers, J
Rooney, J
Wilson, CM
AF Hosek, Sybil
Rudy, Bret
Landovitz, Raphael
Kapogiannis, Bill
Siberry, George
Liu, Nancy
Rutledge, Brandy
Brothers, Jennifer
Rooney, Jim
Wilson, Craig M.
CA Adolescent Med Trials Network HIV
TI An HIV pre-exposure prophylaxis demonstration project and safety study
for young men who have sex with men in the United States (ATN 110)
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Meeting Abstract
C1 [Hosek, Sybil; Brothers, Jennifer] John H Stroger Jr Hosp Cook Cty, Psychiat, Chicago, IL USA.
[Rudy, Bret] NYU Med Ctr, New York, NY 10016 USA.
[Landovitz, Raphael] Univ Calif Los Angeles, Los Angeles, CA USA.
[Kapogiannis, Bill; Siberry, George] NICHD, MPIDB, Bethesda, MD USA.
[Liu, Nancy; Rutledge, Brandy] Westat Corp, Rockville, MD USA.
[Rooney, Jim] Gilead Sci, Foster City, CA USA.
[Wilson, Craig M.] Univ Alabama Birmingham, Birmingham, AL USA.
EM shosek@cookcountyhhs.org
NR 0
TC 0
Z9 0
U1 1
U2 2
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD JUL
PY 2015
VL 18
SU 4
MA TUAC0204LB
DI 10.7448/IAS.18.5.20549
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA CN8FS
UT WOS:000358675700079
ER
PT J
AU Hosseinipour, M
Bisson, G
Miyahara, S
Sun, X
Moses, A
Riviere, C
Kirui, FK
Badal-Faesen, S
Lagat, D
Nyirenda, M
Naidoo, K
Hakim, J
Mugyenyi, P
Henostroza, G
Leger, PD
Lama, JR
Mohapi, L
Alave, J
Mave, V
Veloso, VG
Pillay, S
Kumarasamy, N
Bao, J
Hogg, E
Jones, L
Zolopa, A
Kumwenda, J
Gupta, A
AF Hosseinipour, Mina
Bisson, Greg
Miyahara, Sachiko
Sun, Xin
Moses, Agnes
Riviere, Cynthia
Kirui, Fredrick K.
Badal-Faesen, Sharlaa
Lagat, David
Nyirenda, Mulinda
Naidoo, Kogieleum
Hakim, James
Mugyenyi, Peter
Henostroza, German
Leger, Paul D.
Lama, Javier R.
Mohapi, Lerato
Alave, Jorge
Mave, Vidya
Veloso, Valdilea G.
Pillay, Sandy
Kumarasamy, Nagalingeswaran
Bao, Jing
Hogg, Evelyn
Jones, Lynne
Zolopa, Andrew
Kumwenda, Johnstone
Gupta, Amita
CA Adult AIDS Clin Trials Grp 5274
TI Empiric TB therapy does not decrease early mortality compared to
isoniazid preventive therapy in adults with advanced HIV initiating ART:
results of ACTG A5274 (REMEMBER study)
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Meeting Abstract
C1 [Hosseinipour, Mina; Moses, Agnes] UNC Project, Lilongwe, Malawi.
[Hosseinipour, Mina] Univ N Carolina, Sch Med, Chapel Hill, NC USA.
[Bisson, Greg] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Miyahara, Sachiko; Sun, Xin] Harvard Univ, Harvard Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Riviere, Cynthia; Leger, Paul D.] GHESKIO Ctr, Port Au Prince, Haiti.
[Kirui, Fredrick K.] Kenya Med Res Inst KEMRI, Kisumu, Kenya.
[Badal-Faesen, Sharlaa] Univ Witwatersrand, Dept Med, Clin HIV Res Unit, ZA-2001 Johannesburg, South Africa.
[Lagat, David] Moi Univ, Sch Med, Eldoret, Kenya.
[Nyirenda, Mulinda; Kumwenda, Johnstone] Johns Hopkins Project, Blantyre, Malawi.
[Naidoo, Kogieleum] Ctr AIDS Programme Res South Africa, Durban, South Africa.
[Hakim, James] Univ Zimbabwe, Dept Med, Harare, Zimbabwe.
[Mugyenyi, Peter] Joint Clin Res Ctr, Kampala, Uganda.
[Henostroza, German] Ctr Infect Dis Res, Lusaka, Zambia.
[Lama, Javier R.; Alave, Jorge] Asociac Civil Impacta Saludy Educac, Lima, Peru.
[Mohapi, Lerato] Perinatal HIV Res Unit, Johannesburg, South Africa.
[Mave, Vidya] BJ Med Coll, Johns Hopkins Clin Trials Unit, Pune, Maharashtra, India.
[Veloso, Valdilea G.] Fiocruz MS, Evandro Chagas Natl Inst Infect Dis, BR-21045900 Rio De Janeiro, Brazil.
[Pillay, Sandy] Univ KwaZulu Natal, Durban, South Africa.
[Kumarasamy, Nagalingeswaran] VHS, YRGCARE Med Ctr, Chennai, Tamil Nadu, India.
[Bao, Jing] NIH, Bethesda, MD 20892 USA.
[Hogg, Evelyn] Social & Sci Syst, Silver Spring, MD USA.
[Jones, Lynne] Frontier Sci, Buffalo, NY USA.
[Zolopa, Andrew] Stanford Univ, Palo Alto, CA 94304 USA.
[Gupta, Amita] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
EM mina_hosseinipour@med.unc.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD JUL
PY 2015
VL 18
SU 4
MA MOAB0205LB
DI 10.7448/IAS.18.5.20481
PG 3
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA CN8FS
UT WOS:000358675700024
ER
PT J
AU Kinloch, NN
Macmillan, DR
Le, AQ
Cotton, LA
Mccloskey, R
Bangsberg, DR
Buchbinder, S
Carrington, M
Fuchs, J
Harrigan, PR
Koblin, B
Markowitz, M
Mayer, K
Milloy, MJ
Schechter, MT
Wagner, T
Walker, BD
Carlson, JM
Poon, AFY
Brumme, ZL
AF Kinloch, Natalie Nicole
Macmillan, Daniel R.
Le, Anh Q.
Cotton, Laura A.
Mccloskey, Rosemary
Bangsberg, David R.
Buchbinder, Susan
Carrington, Mary
Fuchs, Jonathan
Harrigan, P. Richard
Koblin, Beryl
Markowitz, Martin
Mayer, Kenneth
Milloy, M. J.
Schechter, Martin T.
Wagner, Theresa
Walker, Bruce D.
Carlson, Jonathan M.
Poon, Art F. Y.
Brumme, Zabrina L.
TI Population-level spread of immune-driven mutations in HIV-1 polymerase
during the North American epidemic
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Meeting Abstract
C1 [Kinloch, Natalie Nicole; Macmillan, Daniel R.; Le, Anh Q.; Cotton, Laura A.; Poon, Art F. Y.; Brumme, Zabrina L.] Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC V5A 1S6, Canada.
[Mccloskey, Rosemary; Harrigan, P. Richard; Milloy, M. J.; Poon, Art F. Y.; Brumme, Zabrina L.] British Columbia Ctr Excellence, Vancouver, BC, Canada.
[Bangsberg, David R.; Walker, Bruce D.] Ragon Inst MGH MIT & Harvard, Cambridge, MA USA.
[Buchbinder, Susan; Fuchs, Jonathan; Wagner, Theresa] San Francisco Dept Publ Hlth, San Francisco, CA USA.
[Carrington, Mary] Frederick Natl Lab Canc Res, Expt Immunol Lab, Frederick, MD USA.
[Fuchs, Jonathan] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Koblin, Beryl] New York Blood Ctr, New York, NY 10021 USA.
[Markowitz, Martin] Aaron Diamond AIDS Res Ctr, New York, NY USA.
[Mayer, Kenneth] Fenway Community Hlth, Boston, MA USA.
[Mayer, Kenneth] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Schechter, Martin T.; Poon, Art F. Y.] Univ British Columbia, Fac Med, Vancouver, BC, Canada.
[Carlson, Jonathan M.] Microsoft Res, Seattle, WA USA.
EM nkinloch@sfu.ca
NR 0
TC 0
Z9 0
U1 0
U2 1
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD JUL
PY 2015
VL 18
SU 4
MA TUAA0103
DI 10.7448/IAS.18.5.20351
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA CN8FS
UT WOS:000358675700049
ER
PT J
AU Lee, S
Chomont, N
Fromentin, R
Silicano, R
Silicano, J
Richman, D
O'Doherty, U
Palmer, S
Burbelo, P
Deeks, S
AF Lee, Sulggi
Chomont, Nicolas
Fromentin, Remi
Silicano, Robert
Silicano, Janet
Richman, Douglas
O'Doherty, Una
Palmer, Sarah
Burbelo, Peter
Deeks, Steven
TI Anti-HIV antibody responses reflect the quantifiable HIV reservoir size
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Meeting Abstract
C1 [Lee, Sulggi; Deeks, Steven] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Chomont, Nicolas; Fromentin, Remi] Univ Montreal, Dept Immunol, Montreal, PQ, Canada.
[Silicano, Robert; Silicano, Janet] Johns Hopkins Univ, Dept Med, Baltimore, MD USA.
[Richman, Douglas] Univ Calif San Diego, Dept Med, La Jolla, CA USA.
[O'Doherty, Una] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA.
[Palmer, Sarah] Univ Sydney, Dept Med, Sydney, NSW 2006, Australia.
[Burbelo, Peter] Natl Inst Dent & Craniofacial Res, Clin Dent Res Core, Bethesda, MD USA.
EM sulggi.lee@ucsf.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD JUL
PY 2015
VL 18
SU 4
MA MOAA0103
DI 10.7448/IAS.18.5.20322
PG 2
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA CN8FS
UT WOS:000358675700004
ER
PT J
AU Liu, A
Cohen, S
Vittinghoff, E
Anderson, P
Doblecki-Lewis, S
Bacon, O
Chege, W
Elion, R
Buchbinder, S
Kolber, M
AF Liu, Albert
Cohen, Stephanie
Vittinghoff, Eric
Anderson, Peter
Doblecki-Lewis, Susanne
Bacon, Oliver
Chege, Wairimu
Elion, Richard
Buchbinder, Susan
Kolber, Michael
CA Project Study Grp
TI Adherence, sexual behaviour and HIV/STI incidence among men who have sex
with men and transgender women in the US PrEP demonstration (Demo)
project
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Meeting Abstract
C1 [Liu, Albert; Cohen, Stephanie; Buchbinder, Susan] San Francisco Dept Publ Hlth, San Francisco, CA USA.
[Liu, Albert; Cohen, Stephanie; Vittinghoff, Eric; Bacon, Oliver; Buchbinder, Susan] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Anderson, Peter] Univ Colorado, Dept Pharmaceut Sci, Aurora, CO USA.
[Doblecki-Lewis, Susanne; Kolber, Michael] Univ Miami, Miami, FL USA.
[Chege, Wairimu] NIH, Bethesda, MD 20892 USA.
[Elion, Richard] Whitman Walker Hlth, Washington, DC USA.
EM albert.liu@sfdph.org
NR 0
TC 0
Z9 0
U1 2
U2 5
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD JUL
PY 2015
VL 18
SU 4
MA TUAC0202
DI 10.7448/IAS.18.5.20371
PG 2
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA CN8FS
UT WOS:000358675700077
ER
PT J
AU Mannheimer, S
Hirsch-Moverman, Y
Loquere, A
Franks, J
Hughes, J
Ou, SS
Amico, KR
Hendrix, C
Dye, BJ
Piwowar-Manning, E
Marzinke, M
Elharrar, V
Stirratt, M
Grant, RM
AF Mannheimer, Sharon
Hirsch-Moverman, Yael
Loquere, Avelino
Franks, Julie
Hughes, James
Ou, San-San
Amico, K. Rivet
Hendrix, Craig
Dye, Bonnie J.
Piwowar-Manning, Estelle
Marzinke, Mark
Elharrar, Vanessa
Stirratt, Michael
Grant, Robert M.
CA HPTN 067 ADAPT Harlem Study Team
TI HPTN 067/ADAPT study: a comparison of daily and intermittent
pre-exposure prophylaxis dosing for HIV prevention in men who have sex
with men and transgender women in New York city
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Meeting Abstract
C1 [Mannheimer, Sharon] Columbia Univ, Dept Med, Harlem Hosp, New York, NY USA.
[Mannheimer, Sharon; Hirsch-Moverman, Yael] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA.
[Mannheimer, Sharon; Hirsch-Moverman, Yael; Loquere, Avelino; Franks, Julie] Columbia Univ, ICAP, Mailman Sch Publ Hlth, New York, NY USA.
[Hughes, James] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Hughes, James; Ou, San-San] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Amico, K. Rivet] Univ Michigan, Dept Hlth Behav & Hlth Educ, Ann Arbor, MI 48109 USA.
[Hendrix, Craig] Johns Hopkins Univ, Dept Med, Baltimore, MD USA.
[Dye, Bonnie J.] FHI 360, Durham, NC USA.
[Piwowar-Manning, Estelle; Marzinke, Mark] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA.
[Elharrar, Vanessa] PSP DAIDS NIAID NIH, Clin Prevent Res Branch, Bethesda, MD USA.
[Stirratt, Michael] NIMH, Div AIDS Res, Bethesda, MD 20892 USA.
[Grant, Robert M.] Univ Calif San Francisco, Gladstone Inst, San Francisco, CA 94143 USA.
EM sbm20@columbia.edu
RI Hendrix, Craig/G-4182-2014
OI Hendrix, Craig/0000-0002-5696-8665
NR 0
TC 0
Z9 0
U1 0
U2 3
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD JUL
PY 2015
VL 18
SU 4
MA MOAC0305LB
DI 10.7448/IAS.18.5.20538
PG 2
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA CN8FS
UT WOS:000358675700040
ER
PT J
AU Micci, L
Ryan, E
Fromentin, R
Benne, C
Chomont, N
Lifson, J
Paiardini, M
AF Micci, Luca
Ryan, Emily
Fromentin, Remi
Benne, Clarisse
Chomont, Nicolas
Lifson, Jeffrey
Paiardini, Mirko
TI Virologic and immunologic correlates of viral control post-ART
interruption in SIV-infected rhesus macaques
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Meeting Abstract
C1 [Micci, Luca; Ryan, Emily; Paiardini, Mirko] Emory Univ, YNPRC, Atlanta, GA 30322 USA.
[Fromentin, Remi; Chomont, Nicolas] Univ Montreal, Dept Microbiol Infectiol & Immunol, Montreal, PQ, Canada.
[Benne, Clarisse] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Lifson, Jeffrey] NCI, NIH, Frederick, MD 21701 USA.
EM mirko.paiardini@emory.edu
NR 0
TC 0
Z9 0
U1 0
U2 1
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD JUL
PY 2015
VL 18
SU 4
MA MOAA0102
DI 10.7448/IAS.18.5.20321
PG 2
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA CN8FS
UT WOS:000358675700003
ER
PT J
AU Nair, G
Justman, JE
Piper, J
Marzinke, M
Hendrix, C
Dai, J
Pan, J
Galaska, B
Levy, L
Shwartz, J
McGowan, I
Dezutti, C
AF Nair, Gonasagrie
Justman, Jessica E.
Piper, Jeanna
Marzinke, Mark
Hendrix, Craig
Dai, James
Pan, Jason
Galaska, Beth
Levy, Lisa
Shwartz, Jill
McGowan, Ian
Dezutti, Charlene
TI Pharmacokinetics and pharmacodynamics of tenofovir reduced-glycerin 1%
gel in the rectal and vaginal compartments in women: a
cross-compartmental study with directly observed dosing
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Meeting Abstract
C1 [Nair, Gonasagrie] Univ KwaZulu Natal, Ctr AIDS Programme Res South Africa CAPRISA, Durban, South Africa.
[Justman, Jessica E.] Columbia Univ, ICAP, New York, NY USA.
[Piper, Jeanna] NIAID, DAIDS, Bethesda, MD 20892 USA.
[Marzinke, Mark; Hendrix, Craig] Johns Hopkins Univ, Baltimore, MD USA.
[Dai, James; Pan, Jason] FHCRC SCHARP, Seattle, WA USA.
[Galaska, Beth; Dezutti, Charlene] Microbicides Trial Network, Pittsburgh, PA USA.
[Levy, Lisa] FHI 360, Washington, DC USA.
[Shwartz, Jill] CONRAD, Arlington, VA USA.
[McGowan, Ian] Univ Pittsburgh, Magee Womens Res Inst, Pittsburgh, PA USA.
EM jj2158@columbia.edu
RI Hendrix, Craig/G-4182-2014
OI Hendrix, Craig/0000-0002-5696-8665
NR 0
TC 0
Z9 0
U1 0
U2 1
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD JUL
PY 2015
VL 18
SU 4
MA TUAC0206LB
DI 10.7448/IAS.18.5.20551
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA CN8FS
UT WOS:000358675700081
ER
PT J
AU Pettifor, A
MacPhail, C
Selin, A
Gomez-Olive, X
Hughes, J
Wagner, R
Mabuza, W
Mokoena, I
Eshleman, S
Piwowar-Manning, E
Twine, R
Julien, A
Marcus, C
Andrew, P
Wang, J
Xing, Y
McKinstry, L
Hamilton, E
Agyei, Y
Allison, S
Sato, P
Townley, E
Tollman, S
Kahn, K
AF Pettifor, Audrey
MacPhail, Catherine
Selin, Amanda
Gomez-Olive, Xavier
Hughes, James
Wagner, Ryan
Mabuza, Wonderful
Mokoena, Immitrude
Eshleman, Susan
Piwowar-Manning, Estelle
Twine, Rhian
Julien, Aimee
Marcus, Cheryl
Andrew, Philip
Wang, Jing
Xing, Yi
McKinstry, Laura
Hamilton, Erica
Agyei, Yaw
Allison, Susannah
Sato, Paul
Townley, Ellen
Tollman, Stephen
Kahn, Kathleen
CA HPTN 068 Study Team
TI HPTN 068 conditional cash transfer to prevent HIV infection among young
women in South Africa: results of a randomized controlled trial
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Meeting Abstract
C1 [Pettifor, Audrey] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Pettifor, Audrey] Univ Witwatersrand, Sch Publ Hlth, Johannesburg, South Africa.
[MacPhail, Catherine] Univ New England, Armindale, Australia.
[Selin, Amanda; Julien, Aimee] Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC USA.
[Gomez-Olive, Xavier; Wagner, Ryan; Mabuza, Wonderful; Mokoena, Immitrude; Twine, Rhian; Tollman, Stephen; Kahn, Kathleen] Univ Witwatersrand, Sch Publ Hlth, MRC Wits Rural Publ Hlth & Hlth Transit Unit, Johannesburg, South Africa.
[Hughes, James; Wang, Jing; Xing, Yi; McKinstry, Laura] Univ Washington, Seattle, WA 98195 USA.
[Eshleman, Susan; Piwowar-Manning, Estelle; Agyei, Yaw] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Marcus, Cheryl] Univ N Carolina, Sch Med, Chapel Hill, NC USA.
[Andrew, Philip; Hamilton, Erica] FHI 360, Durham, NC USA.
[Allison, Susannah] NIMH, Div AIDS Res, NIH, Rockville, MD 20857 USA.
[Sato, Paul] NIH, Off AIDS Res, Bethesda, MD 20892 USA.
[Townley, Ellen] NIAID, DAIDS, NIH, Rockville, MD USA.
EM apettif@email.unc.edu
NR 0
TC 1
Z9 1
U1 0
U2 4
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD JUL
PY 2015
VL 18
SU 4
MA TUAC0106LB
DI 10.7448/IAS.18.5.20548
PG 2
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA CN8FS
UT WOS:000358675700075
ER
PT J
AU Prentice, H
Tomaras, G
Geraghty, D
Apps, R
Fong, YY
Ehrenberg, P
Rolland, M
Kijak, G
Nelson, W
Decamp, A
Shen, XY
Yates, N
Zolla-Pazner, S
Nitayaphan, S
Rerks-Ngarm, S
Pitisuttithum, P
Ferrari, G
Montefiori, D
McElrath, J
Bailer, R
Koup, R
O'Connell, R
Robb, M
Michael, N
Kim, J
Thomas, R
AF Prentice, Heather
Tomaras, Georgia
Geraghty, Daniel
Apps, Richard
Fong, Youyi
Ehrenberg, Philip
Rolland, Morgane
Kijak, Gustavo
Nelson, Wyatt
Decamp, Allan
Shen, Xiaoying
Yates, Nicole
Zolla-Pazner, Susan
Nitayaphan, Sorachai
Rerks-Ngarm, Supachai
Pitisuttithum, Punnee
Ferrari, Guido
Montefiori, David
McElrath, Juliana
Bailer, Robert
Koup, Richard
O'Connell, Robert
Robb, Merlin
Michael, Nelson
Kim, Jerome
Thomas, Rasmi
TI HIV-1-specific IgG antibody levels correlate with the presence of a
specific HLA class II allele to impact acquisition and vaccine efficacy
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Meeting Abstract
C1 [Prentice, Heather; Ehrenberg, Philip; Rolland, Morgane; Kijak, Gustavo; Robb, Merlin; Michael, Nelson; Kim, Jerome; Thomas, Rasmi] Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD USA.
[Tomaras, Georgia; Shen, Xiaoying; Yates, Nicole; Ferrari, Guido; Montefiori, David] Duke Univ, Sch Med, Durham, NC 27706 USA.
[Geraghty, Daniel; Fong, Youyi; Nelson, Wyatt; Decamp, Allan; McElrath, Juliana] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Apps, Richard] Leidos Inc, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Zolla-Pazner, Susan] NYU, Sch Med, New York, NY USA.
[Nitayaphan, Sorachai; O'Connell, Robert] AFRIMS, Bangkok, Thailand.
[Rerks-Ngarm, Supachai] Minist Publ Hlth, Nonthaburi, Thailand.
[Pitisuttithum, Punnee] Mahidol Univ, Bangkok 10700, Thailand.
[Bailer, Robert; Koup, Richard] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA.
EM rthomas@hivresearch.org
RI Tomaras, Georgia/J-5041-2016
NR 0
TC 0
Z9 0
U1 0
U2 3
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD JUL
PY 2015
VL 18
SU 4
MA TUAA0106LB
DI 10.7448/IAS.18.5.20541
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA CN8FS
UT WOS:000358675700052
ER
PT J
AU Lee, MS
Jeong, MH
Lee, HW
Han, HJ
Ko, A
Hewitt, SM
Kim, JH
Chun, KH
Chung, JY
Lee, C
Cho, H
Song, J
AF Lee, Min-Sik
Jeong, Man-Hyung
Lee, Hyun-Woo
Han, Hyun-Ji
Ko, Aram
Hewitt, Stephen M.
Kim, Jae-Hoon
Chun, Kyung-Hee
Chung, Joon-Yong
Lee, Cheolju
Cho, Hanbyoul
Song, Jaewhan
TI PI3K/AKT activation induces PTEN ubiquitination and destabilization
accelerating tumourigenesis
SO NATURE COMMUNICATIONS
LA English
DT Article
ID POSTTRANSLATIONAL REGULATION; GERMLINE MUTATIONS; TUMOR SUPPRESSION;
CANCER; GENE; DEGRADATION; APOPTOSIS; PATHWAY; LIGASE; CELLS
AB The activity of the phosphatase and tensin homologue (PTEN) is known to be suppressed via post-translational modification. However, the mechanism and physiological significance by which post-translational modifications lead to PTEN suppression remain unclear. Here we demonstrate that PTEN destabilization is induced by EGFR-or oncogenic PI3K mutation-mediated AKT activation in cervical cancer. EGFR/PI3K/AKT-mediated ubiquitination and degradation of PTEN are dependent on the MKRN1 E3 ligase. These processes require the stabilization of MKRN1 via AKT-mediated phosphorylation. In cervical cancer patients with high levels of pAKT and MKRN1 expression, PTEN protein levels are low and correlate with a low 5-year survival rate. Taken together, our results demonstrate that PI3K/AKT signals enforce positive-feedback regulation by suppressing PTEN function.
C1 [Lee, Min-Sik; Jeong, Man-Hyung; Han, Hyun-Ji; Ko, Aram; Song, Jaewhan] Yonsei Univ, Coll Life Sci & Biotechnol, Dept Biochem, Seoul 120749, South Korea.
[Lee, Hyun-Woo; Chun, Kyung-Hee] Yonsei Univ, Coll Med, Dept Biochem & Mol Biol, Seoul 120752, South Korea.
[Hewitt, Stephen M.; Chung, Joon-Yong] NCI, Expt Pathol Lab, Ctr Canc Res, NIH MSC 1500, Bethesda, MD 20892 USA.
[Kim, Jae-Hoon; Cho, Hanbyoul] Yonsei Univ, Coll Med, Gangnam Severance Hosp, Dept Obstet & Gynecol, Seoul 135720, South Korea.
[Kim, Jae-Hoon; Cho, Hanbyoul] Yonsei Univ, Coll Med, Inst Womens Life Med Sci, Seoul 120752, South Korea.
[Lee, Cheolju] Korea Inst Sci & Technol, BRI, Seoul 136791, South Korea.
RP Cho, H (reprint author), Yonsei Univ, Coll Med, Gangnam Severance Hosp, Dept Obstet & Gynecol, Seoul 135720, South Korea.
EM hanbyoul@yuhs.ac; jso678@yonsei.ac.kr
OI Hewitt, Stephen/0000-0001-8283-1788; Chung,
Joon-Yong/0000-0001-5041-5982
FU Korea Healthcare Technology R&D Project, Ministry for Health & Welfare
Affairs, Republic of Korea [A121387]; National Cancer Center, Korea
[NCC-1420300]; National Research Foundation of Korea
[NRF-2013H1A8A1004182]; Intramural Research Program of the NIH, National
Cancer Institute, Center for Cancer Research; Brain Korea 21 (BK21)
Program
FX This work was supported by the Korea Healthcare Technology R&D Project,
Ministry for Health & Welfare Affairs, Republic of Korea (A121387), the
National Cancer Center, Korea (NCC-1420300), the National Research
Foundation of Korea (NRF-2013H1A8A1004182) and the Intramural Research
Program of the NIH, National Cancer Institute, Center for Cancer
Research. M.-S.L. was a fellowship awardee by the Brain Korea 21 (BK21)
Program.
NR 41
TC 10
Z9 12
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD JUL
PY 2015
VL 6
AR 7769
DI 10.1038/ncomms8769
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CO0RK
UT WOS:000358859700006
PM 26183061
ER
PT J
AU Luo, YX
Xue, YX
Liu, JF
Shi, HS
Jian, M
Han, Y
Zhu, WL
Bao, YP
Wu, P
Ding, ZB
Shen, HW
Shi, J
Shaham, Y
Lu, L
AF Luo, Yi-xiao
Xue, Yan-xue
Liu, Jian-feng
Shi, Hai-shui
Jian, Min
Han, Ying
Zhu, Wei-li
Bao, Yan-ping
Wu, Ping
Ding, Zeng-bo
Shen, Hao-wei
Shi, Jie
Shaham, Yavin
Lu, Lin
TI A novel UCS memory retrieval-extinction procedure to inhibit relapse to
drug seeking
SO NATURE COMMUNICATIONS
LA English
DT Article
ID NUCLEUS-ACCUMBENS CORE; CONDITIONED PLACE PREFERENCE; AMPA RECEPTOR
ENDOCYTOSIS; LONG-TERM DEPRESSION; COCAINE-SEEKING; BASOLATERAL
AMYGDALA; FEAR MEMORY; BEHAVIORAL SENSITIZATION; INDUCED REINSTATEMENT;
SIGNALING PATHWAY
AB We recently reported that a conditioned stimulus (CS) memory retrieval-extinction procedure decreases reinstatement of cocaine and heroin seeking in rats and heroin craving in humans. Here we show that non-contingent cocaine or methylphenidate injections (UCS retrieval) 1 h before the extinction sessions decreases cocaine-priming-induced reinstatement, spontaneous recovery, and renewal of cocaine seeking in rats. Unlike the CS-based memory retrieval-extinction procedure, the UCS memory retrieval manipulation decreases renewal and reinstatement of cocaine seeking in the presence of cocaine cues that were not present during extinction training and also decreases cocaine seeking when the procedure commences after 28 days of abstinence. The inhibitory effect of the UCS retrieval manipulation on cocaine-priming-induced reinstatement is mediated by regulation of AMPA-receptor endocytosis in the basolateral amygdala. The UCS memory retrieval-extinction procedure has superior relapse prevention characteristics than the CS memory retrieval-extinction procedure and could be a promising method for decreasing relapse in human addicts.
C1 [Luo, Yi-xiao; Liu, Jian-feng; Jian, Min; Han, Ying; Lu, Lin] Peking Univ, Key Lab Mental Hlth, Inst Mental Hlth, Hosp 6, Beijing 100191, Peoples R China.
[Luo, Yi-xiao; Xue, Yan-xue; Liu, Jian-feng; Jian, Min; Han, Ying; Zhu, Wei-li; Bao, Yan-ping; Wu, Ping; Ding, Zeng-bo; Shen, Hao-wei; Shi, Jie; Lu, Lin] Peking Univ, Beijing Key Lab Drug Dependence Res, Natl Inst Drug Dependence, Beijing 100191, Peoples R China.
[Shi, Hai-shui] Hebei Med Univ, Basic Med Coll, Dept Biochem & Mol Biol, Shijiazhuang 050017, Peoples R China.
[Shaham, Yavin] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Lu, Lin] Peking Univ, McGovern Inst Brain Res, Peking Tsinghua Ctr Life Sci, PKU IDG, Beijing 100871, Peoples R China.
RP Lu, L (reprint author), Peking Univ, Key Lab Mental Hlth, Inst Mental Hlth, Hosp 6, Beijing 100191, Peoples R China.
EM linlu@bjmu.edu.cn
OI Liu, Jianfeng/0000-0002-3464-6462
FU National Basic Research Program of China [2015CB856400, 2015CB553503];
Natural Science Foundation of China [31230033, 81221002, 91432303]; NIDA
FX This work was supported in part by the National Basic Research Program
of China (no. 2015CB856400 and 2015CB553503) and the Natural Science
Foundation of China (no. 31230033, 81221002 and 91432303). The
preparation of the manuscript was also supported in part by the
Intramural Research Program of NIDA. We thank Robyn St. Laurent, Shi-Qiu
Meng and Chen Chen for editorial assistance and Dr Dorit Ron (UCSF) for
helpful comments and advice on the Western Blot assays.
NR 70
TC 7
Z9 9
U1 4
U2 23
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD JUL
PY 2015
VL 6
AR 7675
DI 10.1038/ncomms8675
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CO0QW
UT WOS:000358858100019
PM 26169171
ER
PT J
AU Sun, L
Zhang, XZ
Gao, S
Rao, PA
Padilla-Sanchez, V
Chen, ZG
Sun, SY
Xiang, Y
Subramaniam, S
Rao, VB
Rossmann, MG
AF Sun, Lei
Zhang, Xinzheng
Gao, Song
Rao, Prashant A.
Padilla-Sanchez, Victor
Chen, Zhenguo
Sun, Siyang
Xiang, Ye
Subramaniam, Sriram
Rao, Venigalla B.
Rossmann, Michael G.
TI Cryo-EM structure of the bacteriophage T4 portal protein assembly at
near-atomic resolution
SO NATURE COMMUNICATIONS
LA English
DT Article
ID DNA-PACKAGING MACHINE; MOLECULAR ARCHITECTURE; ELECTRON-MICROSCOPY;
CAPSID STRUCTURE; ATP HYDROLYSIS; MOTOR; TRANSLOCATION; MECHANISM;
PHI-29; HEAD
AB The structure and assembly of bacteriophage T4 has been extensively studied. However, the detailed structure of the portal protein remained unknown. Here we report the structure of the bacteriophage T4 portal assembly, gene product 20 (gp20), determined by cryo-electron microscopy (cryo-EM) to 3.6 angstrom resolution. In addition, analysis of a 10 angstrom resolution cryo-EM map of an empty prolate T4 head shows how the dodecameric portal assembly interacts with the capsid protein gp23 at the special pentameric vertex. The gp20 structure also verifies that the portal assembly is required for initiating head assembly, for attachment of the packaging motor, and for participation in DNA packaging. Comparison of the Myoviridae T4 portal structure with the known portal structures of phi 29, SPP1 and P22, representing Podo- and Siphoviridae, shows that the portal structure probably dates back to a time when self-replicating microorganisms were being established on Earth.
C1 [Sun, Lei; Zhang, Xinzheng; Chen, Zhenguo; Sun, Siyang; Xiang, Ye; Rossmann, Michael G.] Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA.
[Gao, Song; Padilla-Sanchez, Victor; Rao, Venigalla B.] Catholic Univ Amer, Dept Biol, Washington, DC 20064 USA.
[Rao, Prashant A.; Subramaniam, Sriram] NCI, NIH, Bethesda, MD 20892 USA.
RP Rao, VB (reprint author), Catholic Univ Amer, Dept Biol, 620 Michigan Ave N-E, Washington, DC 20064 USA.
EM rao@cua.edu; mr@purdue.edu
RI Zhang , Xinzheng/E-6339-2013
FU NIH [1S10RR23057, 1S10OD018111, DBI-1338135, AI 081726, MCB-1411989];
CNSI at UCLA; National Natural Science Foundation of China [31470275]
FX We thank Sheryl Kelly for helping to prepare the manuscript for
publication. We are very grateful to Hong Zhou and Xing Zhang, from the
University of California, Los Angeles, for making their Titan and K2
Summit detector available for cryo-EM data collection. The authors
acknowledge the use of instruments at the Electron Imaging Center for
NanoMachines supported by NIH (1S10RR23057 and 1S10OD018111), NSF
(DBI-1338135) and CNSI at UCLA. We acknowledge the assistance of Jason
Pierson from NIH-FEI Living Lab for cryo-EM data collection and Mario
Borgnia from National Cancer Institute, National Institutes of Health
(NIH) for cryo-EM data analysis. The work was supported by NIH grant AI
081726 to MGR and VBR and in part by the NSF grant MCB-1411989 to V.B.R.
S.G. was partially supported by the National Natural Science Foundation
of China (Grant No. 31470275).
NR 58
TC 10
Z9 10
U1 5
U2 22
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD JUL
PY 2015
VL 6
AR 7548
DI 10.1038/ncomms8548
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CO0PE
UT WOS:000358853600001
PM 26144253
ER
PT J
AU Wang, LS
Shi, W
Joyce, MG
Modjarrad, K
Zhang, Y
Leung, K
Lees, CR
Zhou, TQ
Yassine, HM
Kanekiyo, M
Yang, ZY
Chen, XJ
Becker, MM
Freeman, M
Vogel, L
Johnson, JC
Olinger, G
Todd, JP
Bagci, U
Solomon, J
Mollura, DJ
Hensley, L
Jahrling, P
Denison, MR
Rao, SS
Subbarao, K
Kwong, PD
Mascola, JR
Kong, WP
Graham, BS
AF Wang, Lingshu
Shi, Wei
Joyce, M. Gordon
Modjarrad, Kayvon
Zhang, Yi
Leung, Kwanyee
Lees, Christopher R.
Zhou, Tongqing
Yassine, Hadi M.
Kanekiyo, Masaru
Yang, Zhi-yong
Chen, Xuejun
Becker, Michelle M.
Freeman, Megan
Vogel, Leatrice
Johnson, Joshua C.
Olinger, Gene
Todd, John P.
Bagci, Ulas
Solomon, Jeffrey
Mollura, Daniel J.
Hensley, Lisa
Jahrling, Peter
Denison, Mark R.
Rao, Srinivas S.
Subbarao, Kanta
Kwong, Peter D.
Mascola, John R.
Kong, Wing-Pui
Graham, Barney S.
TI Evaluation of candidate vaccine approaches for MERS-CoV
SO NATURE COMMUNICATIONS
LA English
DT Article
ID RESPIRATORY SYNDROME CORONAVIRUS; RECEPTOR-BINDING DOMAIN; HUMAN
MONOCLONAL-ANTIBODIES; SPIKE PROTEIN; IMMUNE-RESPONSES; NEUTRALIZING
ANTIBODIES; PROTECTIVE IMMUNITY; RIBI ADJUVANT; SAUDI-ARABIA; DNA
VACCINES
AB The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) as a cause of severe respiratory disease highlights the need for effective approaches to CoV vaccine development. Efforts focused solely on the receptor-binding domain (RBD) of the viral Spike (S) glycoprotein may not optimize neutralizing antibody (NAb) responses. Here we show that immunogens based on full-length S DNA and S1 subunit protein elicit robust serumneutralizing activity against several MERS-CoV strains in mice and non-human primates. Serological analysis and isolation of murine monoclonal antibodies revealed that immunization elicits NAbs to RBD and, non-RBD portions of S1 and S2 subunit. Multiple neutralization mechanisms were demonstrated by solving the atomic structure of a NAb-RBD complex, through sequencing of neutralization escape viruses and by constructing MERS-CoV S variants for serological assays. Immunization of rhesus macaques confers protection against MERS-CoV-induced radiographic pneumonia, as assessed using computerized tomography, supporting this strategy as a promising approach for MERS-CoV vaccine development.
C1 [Wang, Lingshu; Shi, Wei; Joyce, M. Gordon; Modjarrad, Kayvon; Zhang, Yi; Leung, Kwanyee; Lees, Christopher R.; Zhou, Tongqing; Yassine, Hadi M.; Kanekiyo, Masaru; Yang, Zhi-yong; Chen, Xuejun; Todd, John P.; Rao, Srinivas S.; Kwong, Peter D.; Mascola, John R.; Kong, Wing-Pui; Graham, Barney S.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Modjarrad, Kayvon] US Mil HIV Res Program, Walter Reed Army Inst Res, Silver Spring, MD 20910 USA.
[Modjarrad, Kayvon] Henry M Jackson Fdn Adv Mil Med, Bethesda, MD 20817 USA.
[Yang, Zhi-yong] Sanofi Aventis, Cambridge, MA 02139 USA.
[Becker, Michelle M.; Freeman, Megan; Denison, Mark R.] Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA.
[Vogel, Leatrice; Subbarao, Kanta] NIAID, Emerging Resp Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Johnson, Joshua C.; Olinger, Gene; Hensley, Lisa; Jahrling, Peter] NIAID, Integrated Res Facil, NIH, Frederick, MD 21702 USA.
[Bagci, Ulas; Solomon, Jeffrey; Mollura, Daniel J.] NIH, Ctr Infect Dis Imaging, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA.
[Bagci, Ulas] Univ Cent Florida, CRCV, Orlando, FL 32816 USA.
[Denison, Mark R.] Vanderbilt Univ, Dept Pathol Microbiol & Immunol, Med Ctr, Nashville, TN 37232 USA.
RP Kong, WP (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM wkong@niaid.nih.gov; bgraham@nih.gov
RI Zhou, Tongqing/A-6880-2010;
OI Zhou, Tongqing/0000-0002-3935-4637; Bagci, Ulas/0000-0001-7379-6829
FU Intramural Research Program of the Vaccine Research Center, National
Institute of Allergy and Infectious Diseases, NIH; US Department of
Energy, Basic Energy Sciences, Office of Science [W-31-109-Eng-38];
[RO1-AI-108197]
FX We thank members of the Viral Pathogenesis and Virology Laboratories as
well as the Structural Biology and Structural Bioinformatics Sections at
the Vaccine Research Center for insightful comments and helpful
discussions. We also thank Brenda Hartman and Jonathon Stuckey for their
assistance in preparing the figures. The data presented in this
manuscript are tabulated in the main paper and the Supplementary
Materials. Atomic coordinates and structure factors of the reported
crystal structures have been deposited in the Protein Data Bank under
accession codes 4ZPT, 4ZPV and 4ZPW. This work was supported by the
Intramural Research Program of the Vaccine Research Center, National
Institute of Allergy and Infectious Diseases, NIH. Use of sector 22
(SER-CAT) 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. M.R.D, and M.M.B. were supported by
RO1-AI-108197. Research was conducted in compliance with the Animal
Welfare Act and other federal statutes and regulations relating to
animals and experiments involving animals and adheres to principles
stated in the Guide for the Care and Use of Laboratory Animals, NRC
Publication, 2011 edition.
NR 54
TC 21
Z9 24
U1 3
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD JUL
PY 2015
VL 6
AR 7712
DI 10.1038/ncomms8712
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CO0RA
UT WOS:000358858500018
PM 26218507
ER
PT J
AU Azimzadeh, AM
Kelishadi, SS
Ezzelarab, MB
Singh, AK
Stoddard, T
Iwase, H
Zhang, TS
Burdorf, L
Sievert, E
Avon, C
Cheng, XF
Ayares, D
Horvath, KA
Corcoran, PC
Mohiuddin, MM
Barth, RN
Cooper, DKC
Pierson, RN
AF Azimzadeh, Agnes M.
Kelishadi, Sean S.
Ezzelarab, Mohamed B.
Singh, Avneesh K.
Stoddard, Tiffany
Iwase, Hayato
Zhang, Tianshu
Burdorf, Lars
Sievert, Evelyn
Avon, Chris
Cheng, Xiangfei
Ayares, David
Horvath, Keith A.
Corcoran, Philip C.
Mohiuddin, Muhammad M.
Barth, Rolf N.
Cooper, David K. C.
Pierson, Richard N., III
TI Early graft failure of GalTKO pig organs in baboons is reduced by
expression of a human complement pathway-regulatory protein
SO XENOTRANSPLANTATION
LA English
DT Article
DE alpha 1, 3-galactosyltransferase gene-knockout; baboon;
complement-regulatory protein; pig; xenograft rejection;
xenotransplantation
ID GENETICALLY-ENGINEERED PIGS; HUMAN THROMBOMODULIN; ENDOTHELIAL-CELLS;
CARDIAC XENOTRANSPLANTATION; XENOREACTIVE ANTIBODIES;
HEART-TRANSPLANTATION; HYPERACUTE REJECTION; SURVIVAL; ACTIVATION;
XENOGRAFTS
AB We describe the incidence of early graft failure (EGF, defined as loss of function from any cause within 3days after transplant) in a large cohort of GalTKO pig organs transplanted into baboons in three centers, and the effect of additional expression of a human complement pathway-regulatory protein, CD46 or CD55 (GalTKO.hCPRP). Baboon recipients of life-supporting GalTKO kidney (n=7) or heterotopic heart (n=14) grafts received either no immunosuppression (n=4), or one of several partial or full immunosuppressive regimens (n=17). Fourteen additional baboons received a GalTKO.hCPRP kidney (n=5) or heart (n=9) and similar treatment regimens. Immunologic, pathologic, and coagulation parameters were measured at frequent intervals. EGF of GalTKO organs occurred in 9/21 baboons (43%). hCPRP expression reduced the GalTKO EGF incidence to 7% (1/14; P<0.01 vs. GalTKO alone). At 30 mins, complement deposits were more intense in organs in which EGF developed (P<0.005). The intensity of peri-transplant platelet activation (as -thromboglobulin release) correlated with EGF, as did the cumulative coagulation score (P<0.01). We conclude that (i) the transgenic expression of a hCPRP on the vascular endothelium of a GalTKO pig reduces the incidence of EGF and reduces complement deposition, (ii) complement deposition and platelet activation correlate with early GalTKO organ failure, and (iii) the expression of a hCPRP reduces EGF but does not prevent systemic coagulation activation. Additional strategies will be required to control coagulation activation.
C1 [Azimzadeh, Agnes M.; Kelishadi, Sean S.; Stoddard, Tiffany; Zhang, Tianshu; Burdorf, Lars; Sievert, Evelyn; Avon, Chris; Cheng, Xiangfei; Barth, Rolf N.; Pierson, Richard N., III] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Azimzadeh, Agnes M.; Kelishadi, Sean S.; Stoddard, Tiffany; Zhang, Tianshu; Burdorf, Lars; Sievert, Evelyn; Avon, Chris; Cheng, Xiangfei; Barth, Rolf N.; Pierson, Richard N., III] Baltimore VAMC, Baltimore, MD USA.
[Ezzelarab, Mohamed B.; Iwase, Hayato; Cooper, David K. C.] Univ Pittsburgh, Thomas E Starzl Transplantat Inst, Pittsburgh, PA USA.
[Singh, Avneesh K.; Horvath, Keith A.; Corcoran, Philip C.; Mohiuddin, Muhammad M.] NHLBI, Cardiothorac Surg Res Program, NIH, Bethesda, MD 20892 USA.
[Ayares, David] Revivicor, Blacksburg, VA USA.
RP Azimzadeh, AM (reprint author), Univ Maryland, Dept Surg, Sch Med, MSTF Bldg,Room 434C, Baltimore, MD 21201 USA.
EM aazimzadeh@smail.umaryland.edu
RI Barth, Rolf/B-2542-2014; Mohiuddin, Muhammad/M-4642-2013;
OI Mohiuddin, Muhammad/0000-0003-4654-783X; Ezzelarab,
Mohamed/0000-0002-3919-5250
FU NIH [U42 OD011140, U01 AI068642, U01 AI066335, R21 A1074844, U19
A1090959, RR012317-09]; VA Merit award; University of Pittsburgh;
Revivicor, Inc.
FX We thank Walter Schuler, PhD, and his colleagues at the Novartis
Institutes for Biomedical Research (Basel, Switzerland) for making
ABI793 available to us, Roche Pharmaceuticals (Nutley, NJ, USA) for
generously providing mycophenolate mofetil, Genzyme (Cambridge, MA) for
the gift of thymoglobulin and the National Swine Resource and Research
Center for providing the GalTKO.CD55 pigs (funded by NIH grant #U42
OD011140). Work in our laboratories was supported in part by NIH grants
#U01 AI068642, #U01 AI066335, #R21 A1074844, and #U19 A1090959, a VA
Merit award (to RNP), and by Sponsored Research Agreements between the
University of Pittsburgh and Revivicor, Inc. Some of the baboons used in
the study were from the Oklahoma University Health Sciences Center
Division of Animal Resources, which was supported by NIH P40 sponsored
grant RR012317-09, and some by the National Swine Resource and Research
Center, which was supported by NIH grant U42 OD011140.
NR 36
TC 7
Z9 7
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0908-665X
EI 1399-3089
J9 XENOTRANSPLANTATION
JI Xenotransplantation
PD JUL-AUG
PY 2015
VL 22
IS 4
BP 310
EP 316
DI 10.1111/xen.12176
PG 7
WC Medicine, Research & Experimental; Transplantation
SC Research & Experimental Medicine; Transplantation
GA CN8UQ
UT WOS:000358720900008
PM 26174749
ER
PT J
AU Grant, C
Ballard, ED
Olson-Madden, JH
AF Grant, Cynthia
Ballard, Elizabeth D.
Olson-Madden, Jennifer H.
TI An Empowerment Approach to Family Caregiver Involvement in Suicide
Prevention: Implications for Practice
SO FAMILY JOURNAL
LA English
DT Article
DE empowerment; suicide prevention; caregivers; family
ID MENTAL-ILLNESS; HELP-SEEKING; HEALTH-CARE; LIFE EVENTS; INTERVENTION;
BURDEN; IMPACT; DISORDERS; CANCER; MODEL
AB Family members are often intimately involved in the suicidal crisis of a loved one but receive few resources and little support from the mental health community. As a result, these families can experience significant feelings of caregiver burden and powerlessness. This review outlines the experience of caring for a loved one at suicide risk, including potential barriers to involvement, risk and protective factors, and impact on the caregiver. One way to facilitate a caregiver's sense of self-efficacy when working with a suicidal client is to implement an empowerment-based family approach in treatment planning. In this piece, we propose an existing caregiver empowerment model, Creativity, Optimism, Planning and Expert information (COPE), that can be applied to any existing suicide prevention model to assist families in the treatment of clients who are at risk for suicide.
C1 [Grant, Cynthia; Olson-Madden, Jennifer H.] Rocky Mt Mental Illness Res Educ & Clin Ctr MIREC, Denver, CO USA.
[Ballard, Elizabeth D.] NIMH, Bethesda, MD 20892 USA.
[Olson-Madden, Jennifer H.] Univ Colorado, Sch Med, Dept Psychiat & Phys Med & Rehabil, Aurora, CO USA.
RP Grant, C (reprint author), Arapahoe Douglas Mental Hlth Network, 155 Inverness Dr West, Englewood, CO 80111 USA.
EM grant.LCSW@gmail.com
NR 69
TC 2
Z9 2
U1 1
U2 4
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1066-4807
EI 1552-3950
J9 FAM J
JI Fam. J.
PD JUL
PY 2015
VL 23
IS 3
BP 295
EP 304
DI 10.1177/1066480715572962
PG 10
WC Family Studies
SC Family Studies
GA CJ9BT
UT WOS:000355798100010
ER
PT J
AU Ramirez, AS
Leyva, B
Graff, K
Nelson, DE
Huerta, E
AF Ramirez, A. Susana
Leyva, Bryan
Graff, Kaitlin
Nelson, David E.
Huerta, Elmer
TI Seeking Information on Behalf of Others: An Analysis of Calls to a
Spanish-Language Radio Health Program
SO HEALTH PROMOTION PRACTICE
LA English
DT Article
DE information seeking; radio; mass media; Hispanic; Latino; information
inequality; health literacy; doctor patient communication; patient
activation; health promotion; content analysis
ID PATIENT ACTIVATION; CULTURAL COMPETENCE; MEDICAL ENCOUNTER; CANCER;
KNOWLEDGE; ACCULTURATION; PREFERENCES; DISPARITIES; BEHAVIORS; ETHNICITY
AB Objective. Spanish-monolingual Latinos account for 13% of U.S. residents and experience multiple barriers to effective health communication. Information intermediaries/proxies mediate between the linguistically isolated and health care providers. This study characterizes the information needs of surrogate callers and their subjects to a U.S.-based Spanish-language radio health program. Method. Content analysis of calls placed (N = 281 calls). Results. Women made 70% of calls; 39.1% of calls were on behalf of children, 11.0% on behalf of parents/older adults, and 18.5% on behalf of spouses/siblings/contemporary adults. Most common topics were disease symptoms/conditions (19.6%), cancer (13.9%), and reproduction/sexuality (12.9%). Calls for children were more likely than those for parents/other adults to pertain to current illness symptoms or conditions; calls for parents were more likely to be about cancer/chronic conditions. Half of all calls sought clarification about a previous medical encounter. Conclusion: Information-seeking surrogates may represent a useful strategy for linguistic minorities to overcome structural and individual barriers to health information access. Results suggest that Latinos are willing to seek information on behalf of friends and family and highlight the need for improved, culturally and linguistically appropriate health communication sources. Practice Implications. Leveraging Latinos' natural familial social networks/willingness to share information may improve dissemination of culturally and linguistically appropriate health information. Further implications for patient activation and doctor-patient communication are discussed.
C1 [Ramirez, A. Susana] Univ Calif Merced, Merced, CA 95340 USA.
[Leyva, Bryan] Dartmouth Geisel Sch Med, Hanover, NH USA.
[Graff, Kaitlin] Washington Univ, St Louis, MO USA.
[Nelson, David E.] NCI, Bethesda, MD 20892 USA.
[Huerta, Elmer] Washington Hosp Ctr, Washington, DC 20010 USA.
RP Ramirez, AS (reprint author), Univ Calif Merced, Sch Social Sci Humanities & Arts, 5200 North Lake Rd, Merced, CA 95340 USA.
EM sramirez37@ucmerced.edu
NR 34
TC 2
Z9 2
U1 0
U2 3
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1524-8399
EI 1552-6372
J9 HEALTH PROMOT PRACT
JI Health Promot. Pract.
PD JUL
PY 2015
VL 16
IS 4
BP 501
EP 509
DI 10.1177/1524839915574246
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CL9LX
UT WOS:000357301300005
PM 25716191
ER
PT J
AU Kim, HF
Hikosaka, O
AF Kim, Hyoung F.
Hikosaka, Okihide
TI Parallel basal ganglia circuits for voluntary and automatic behaviour to
reach rewards
SO BRAIN
LA English
DT Review
DE basal ganglia; reward value; parallel circuit; voluntary behaviour;
automatic behaviour
ID SACCADIC EYE-MOVEMENTS; NIGRA PARS RETICULATA; PARKINSONS-DISEASE
PATIENTS; MONKEY CAUDATE NEURONS; LONG-TERM RETENTION; MIDBRAIN
DOPAMINERGIC-NEURONS; SUPPLEMENTARY MOTOR AREA; REACTION-TIME-TASK;
SUBSTANTIA-NIGRA; HUNTINGTONS-DISEASE
AB The basal ganglia control body movements, value processing and decision-making. Many studies have shown that the inputs and outputs of each basal ganglia structure are topographically organized, which suggests that the basal ganglia consist of separate circuits that serve distinct functions. A notable example is the circuits that originate from the rostral (head) and caudal (tail) regions of the caudate nucleus, both of which target the superior colliculus. These two caudate regions encode the reward values of visual objects differently: flexible (short-term) values by the caudate head and stable (long-term) values by the caudate tail. These value signals in the caudate guide the orienting of gaze differently: voluntary saccades by the caudate head circuit and automatic saccades by the caudate tail circuit. Moreover, separate groups of dopamine neurons innervate the caudate head and tail and may selectively guide the flexible and stable learning/memory in the caudate regions. Studies focusing on manual handling of objects also suggest that rostrocaudally separated circuits in the basal ganglia control the action differently. These results suggest that the basal ganglia contain parallel circuits for two steps of goal-directed behaviour: finding valuable objects and manipulating the valuable objects. These parallel circuits may underlie voluntary behaviour and automatic skills, enabling animals (including humans) to adapt to both volatile and stable environments. This understanding of the functions and mechanisms of the basal ganglia parallel circuits may inform the differential diagnosis and treatment of basal ganglia disorders.
C1 [Kim, Hyoung F.; Hikosaka, Okihide] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA.
RP Kim, HF (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM hyoung.f.kim@gmail.com
FU Intramural Research Program at the National Institutes of Health,
National Eye Institute
FX This research was supported by the Intramural Research Program at the
National Institutes of Health, National Eye Institute.
NR 320
TC 18
Z9 18
U1 8
U2 31
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-8950
EI 1460-2156
J9 BRAIN
JI Brain
PD JUL 1
PY 2015
VL 138
BP 1776
EP 1800
DI 10.1093/brain/awv134
PN 7
PG 25
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CN6HY
UT WOS:000358536600014
PM 25981958
ER
PT J
AU McLaughlin, G
Morris, N
Kavanagh, PV
Power, JD
Twamley, B
O'Brien, J
Talbot, B
Dowling, G
Mahony, O
Brandt, SD
Patrick, J
Archer, RP
Partilla, JS
Baumann, MH
AF McLaughlin, Gavin
Morris, Noreen
Kavanagh, Pierce V.
Power, John D.
Twamley, Brendan
O'Brien, John
Talbot, Brian
Dowling, Geraldine
Mahony, Olivia
Brandt, Simon D.
Patrick, Julian
Archer, Roland P.
Partilla, John S.
Baumann, Michael H.
TI Synthesis, characterization, and monoamine transporter activity of the
new psychoactive substance 3',4'-methylenedioxy-4-methylaminorex (MDMAR)
SO DRUG TESTING AND ANALYSIS
LA English
DT Article
DE new psychoactive substances; aminorex; psychostimulants; 4,4'-DMAR;
forensic
ID PULMONARY-HYPERTENSION; CLINICAL TOXICOLOGY; AMINOREX;
2-AMINO-5-ARYL-2-OXAZOLINES; 4-METHYLAMINOREX; STEREOISOMERS; DRUGS
AB The recent occurrence of deaths associated with the psychostimulant cis-4,4-dimethylaminorex (4,4-DMAR) in Europe indicated the presence of a newly emerged psychoactive substance on the market. Subsequently, the existence of 3,4-methylenedioxy-4-methylaminorex (MDMAR) has come to the authors' attention and this study describes the synthesis of cis- and trans-MDMAR followed by extensive characterization by chromatographic, spectroscopic, mass spectrometric platforms and crystal structure analysis. MDMAR obtained from an online vendor was subsequently identified as predominantly the cis-isomer (90%). Exposure of the cis-isomer to the mobile phase conditions (acetonitrile/water 1:1 with 0.1% formic acid) employed for high performance liquid chromatography analysis showed an artificially induced conversion to the trans-isomer, which was not observed when characterized by gas chromatography. Monoamine release activities of both MDMAR isomers were compared with the non-selective monoamine releasing agent (+)-3,4-methylenedioxymethamphetamine (MDMA) as a standard reference compound. For additional comparison, both cis- and trans-4,4-DMAR, were assessed under identical conditions. cis-MDMAR, trans-MDMAR, cis-4,4-DMAR and trans-4,4-DMAR were more potent than MDMA in their ability to function as efficacious substrate-type releasers at the dopamine (DAT) and norepinephrine (NET) transporters in rat brain tissue. While cis-4,4-DMAR, cis-MDMAR and trans-MDMAR were fully efficacious releasing agents at the serotonin transporter (SERT), trans-4,4-DMAR acted as a fully efficacious uptake blocker. Currently, little information is available about the presence of MDMAR on the market but the high potency of ring-substituted methylaminorex analogues at all three monoamine transporters investigated here might be relevant when assessing the potential for serious side-effects after high dose exposure. Copyright (C) 2014 John Wiley & Sons, Ltd.
C1 [McLaughlin, Gavin; Morris, Noreen] Athlone Inst Technol, Sch Sci, Dept Life & Phys Sci, Athlone, Westmeath, Ireland.
[McLaughlin, Gavin; Kavanagh, Pierce V.; Power, John D.] St James Hosp, Dept Pharmacol & Therapeut, Sch Med, Trinity Ctr Hlth Sci, Dublin 8, Ireland.
[Power, John D.] Garda HQ, Forens Sci Lab, Dublin 8, Ireland.
[Twamley, Brendan] Univ Dublin Trinity Coll, TCD Small Mol Xray Facil, Dublin 2, Ireland.
[O'Brien, John] Univ Dublin Trinity Coll, Sch Chem, Dublin 2, Ireland.
[Talbot, Brian] Univ Dublin Trinity Coll, Sch Pharm & Pharmaceut Sci, Dublin 2, Ireland.
[Dowling, Geraldine] State Lab, Celbridge, Kildare, Ireland.
[Mahony, Olivia] Dublin Inst Technol, Sch Chem & Pharmaceut Sci, Dublin 2, Ireland.
[Brandt, Simon D.] Liverpool John Moores Univ, Sch Pharm & Biomol Sci, Liverpool L3 5UX, Merseyside, England.
[Patrick, Julian] Sci Supplies Ltd, London W1S 1YH, England.
[Archer, Roland P.] States Analysts Lab, St Martins GY4 6LD, Guernsey, England.
[Partilla, John S.; Baumann, Michael H.] NIDA, Designer Drug Res Unit, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP McLaughlin, G (reprint author), St James Hosp, Dept Pharmacol & Therapeut, Sch Med, Trinity Ctr Hlth Sci, Dublin 8, Ireland.
EM gavinmclaughlin@research.ait.ie
OI McLaughlin, Gavin/0000-0002-2496-8396; Dowling, Dr.
Geraldine/0000-0001-8344-6582
FU National Institute on Drug Abuse, National Institutes of Health, USA
FX Portions of this research were generously supported by the National
Institute on Drug Abuse, National Institutes of Health, USA.
NR 29
TC 2
Z9 2
U1 3
U2 17
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1942-7603
EI 1942-7611
J9 DRUG TEST ANAL
JI Drug Test. Anal.
PD JUL
PY 2015
VL 7
IS 7
BP 555
EP 564
DI 10.1002/dta.1732
PG 10
WC Biochemical Research Methods; Chemistry, Analytical; Pharmacology &
Pharmacy
SC Biochemistry & Molecular Biology; Chemistry; Pharmacology & Pharmacy
GA CN7JR
UT WOS:000358611000001
PM 25331619
ER
PT J
AU Concheiro, M
Newmeyer, MN
da Costa, JL
Flegel, R
Gorelick, DA
Huestis, MA
AF Concheiro, Marta
Newmeyer, Matthew N.
da Costa, Jose Luiz
Flegel, Ron
Gorelick, David A.
Huestis, Marilyn A.
TI Morphine and codeine in oral fluid after controlled poppy seed
administration
SO DRUG TESTING AND ANALYSIS
LA English
DT Article
DE oral fluid; poppy seeds; screening; morphine; codeine
ID URINE; CONSUMPTION; INGESTION
AB Opiates are an important drug class in drug testing programmes. Ingestion of poppy seeds containing morphine and codeine can yield positive opiate tests and mislead result interpretation in forensic and clinical settings. Multiple publications evaluated urine opiate concentrations following poppy seed ingestion, but only two addressed oral fluid (OF) results; neither provided the ingested morphine and codeine dosage. We administered two 45g raw poppy seed doses, each containing 15.7mg morphine and 3.1mg codeine, 8h apart to 17 healthy adults. All OF specimens were screened by on-site OF immunoassay Draeger DrugTest 5000, and confirmed with OF collected with Oral-Eze (R) device and quantified by liquid chromatography-tandem mass spectrometry (1 mu g/L morphine and codeine limits of quantification). Specimens (n=459) were collected before and up to 32h after the first dose. All specimens screened positive 0.5h after dosing and remained positive for 0.5-13h at Draeger 20 mu g/L morphine cut-off. Maximum OF morphine and codeine concentrations (C-max) were 177 and 32.6 mu g/L, with times to C-max (T-max) of 0.5-1h and 0.5-2.5h post-dose, respectively. Windows of detection after the second dose extended at least 24h for morphine and to 18h for codeine. After both doses, the last morphine positive OF result was 1h with 40 mu g/L 2004 proposed US Substance Abuse and Mental Health Services Administration cut-off, and 0.5h with 95 mu g/L cut-off, recently recommended by the Driving under the Influence of Drugs and Medicines project. Positive OF morphine results are possible 0.5-1h after ingestion of 15.7mg of morphine in raw poppy seeds, depending on the cut-off employed. Copyright (C) 2014 John Wiley & Sons, Ltd.
C1 [Concheiro, Marta; Newmeyer, Matthew N.; da Costa, Jose Luiz; Gorelick, David A.; Huestis, Marilyn A.] NIDA, Chem & Drug Metab Sect, IRP, NIH, Baltimore, MD 21224 USA.
[Newmeyer, Matthew N.] Univ Maryland, Toxicol Program, Baltimore, MD 21201 USA.
[da Costa, Jose Luiz] Criminalist Inst Sao Paulo, Forens Toxicol & Chem Lab, Sao Paulo, SP, Brazil.
[Flegel, Ron] US Dept HHS, Div Workplace Programs, Subst Abuse Mental Hlth Serv Adm, Rockville, MD USA.
[Gorelick, David A.] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA.
RP Huestis, MA (reprint author), NIDA, Chem & Drug Metab, Intramural Res Program, NIH, 251 Bayview Blvd,Suite 200 Room 05A-721, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
RI Costa, Jose/C-1741-2012;
OI Costa, Jose/0000-0001-9954-0899; Newmeyer, Matthew/0000-0002-0653-1553
FU Division of Workplace Programs, Substance Abuse and Mental Health
Services Administration; NIDA Intramural Research Program (IRP); NIH
FX We acknowledge funding provided by the Division of Workplace Programs,
Substance Abuse and Mental Health Services Administration and NIDA
Intramural Research Program (IRP), NIH; contributions by the clinical
staff of the NIDA IRP, Behavioral Pharmacology Research Unit, and
Clinical Research Unit, Johns Hopkins Bayview Medical Center. The
authors also thank Megan Taylor, Clinical Protocol Coordinator, CDM,
NIDA IRP, for her valuable assistance.
NR 15
TC 2
Z9 2
U1 0
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1942-7603
EI 1942-7611
J9 DRUG TEST ANAL
JI Drug Test. Anal.
PD JUL
PY 2015
VL 7
IS 7
BP 586
EP 591
DI 10.1002/dta.1742
PG 6
WC Biochemical Research Methods; Chemistry, Analytical; Pharmacology &
Pharmacy
SC Biochemistry & Molecular Biology; Chemistry; Pharmacology & Pharmacy
GA CN7JR
UT WOS:000358611000004
PM 25345619
ER
PT J
AU Song, M
Kang, D
Yang, JJ
Choi, JY
Sung, H
Lee, Y
Yoon, HS
Choi, Y
Kong, SH
Lee, HJ
Yang, HK
Kim, WH
AF Song, Minkyo
Kang, Daehee
Yang, Jae Jeong
Choi, Ji-Yeob
Sung, Hyuna
Lee, Yunhee
Yoon, Hyung-Suk
Choi, Yunhee
Kong, Seong-Ho
Lee, Hyuk-Joon
Yang, Han-Kwang
Kim, Woo Ho
TI Age and sex interactions in gastric cancer incidence and mortality
trends in Korea
SO GASTRIC CANCER
LA English
DT Article
DE Stomach cancer; Epidemiology; Incidence; Mortality; Trend
ID MALE PREDOMINANCE; US ADULTS; BODY-MASS; ADENOCARCINOMA; EPIDEMIOLOGY;
CARDIA; RISK; ESOPHAGUS; TOBACCO; JAPAN
AB The incidence and mortality of gastric cancer have declined rapidly over the past few decades, but reverse trends in the young generation's differential between sexes in some races have been reported in recent years. To investigate whether this divergent trend can be observed in Korea, a country with the highest incidence in the world, age- and sex-specific incidence and mortality trends were evaluated.
Gastric cancer incidence data for the years 1999-2010 and mortality data for the years 1983-2012 were obtained from the Korea Central Cancer Registry and National Statistical Office. Annual percentage changes were calculated by age group (20-39, 40-54, 55-69, 70-79) using Joinpoint regression analysis. Furthermore, age-period-cohort analysis was evaluated.
Overall age-standardized gastric cancer incidence in adults aged between 20 and 79 was declining at a nonsignificant average annual percentage change (AAPC) of -0.2 % in males and -0.4 % in females in Korea during 1999-2010. Mortality was steeper at a significant rate of -4.3 and -5.9 % in males and females, respectively. However, age-specific analysis revealed a flat (males 0.2 %, 95 % CI -0.5-0.6) or increasing incidence trend (females 1.7 %, 95 % CI 0.9-2.5) in the 40-54 age group. APC analysis confirmed the decreasing incidence and mortality trend mainly by the cohort effect.
The differential pattern between males and females in different age groups suggests a possible effect of detection by screening practice or a signal of the change in epidemiological factors in the incidence and mortality of gastric cancer that warrants further studies.
C1 [Song, Minkyo; Kang, Daehee; Yang, Jae Jeong; Lee, Yunhee; Yoon, Hyung-Suk] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea.
[Song, Minkyo; Kang, Daehee; Yang, Jae Jeong; Lee, Yunhee; Yoon, Hyung-Suk] Seoul Natl Univ, Coll Med, Dept Biomed Sci, Seoul, South Korea.
[Song, Minkyo; Yang, Jae Jeong; Yoon, Hyung-Suk] Seoul Natl Univ, Med Res Ctr, Inst Environm Med, Seoul, South Korea.
[Kang, Daehee; Choi, Ji-Yeob; Kong, Seong-Ho; Lee, Hyuk-Joon; Yang, Han-Kwang] Seoul Natl Univ, Coll Med, Canc Res Inst, Dept Prevent Med, Seoul, South Korea.
[Sung, Hyuna] NCI, Div Epidemiol & Genet, Rockville, MD USA.
[Choi, Yunhee] Seoul Natl Univ Hosp, Med Res Collaborating Ctr, Seoul 110744, South Korea.
[Kong, Seong-Ho; Lee, Hyuk-Joon; Yang, Han-Kwang] Seoul Natl Univ, Coll Med, Dept Surg, Seoul, South Korea.
[Kim, Woo Ho] Seoul Natl Univ, Coll Med, Dept Pathol, Seoul 151, South Korea.
RP Kang, D (reprint author), Seoul Natl Univ, Coll Med, Canc Res Inst, Dept Prevent Med, 103 Yongon Daehangno, Seoul, South Korea.
EM dhkang@snu.ac.kr
OI Song, Minkyo/0000-0002-9412-2871
FU BRL (Basic Research Laboratory) program through the National Research
Foundation of Korea - Ministry of Education, Science and Technology
[2012-0000347]; National Research Foundation of Korea (NRF) A3 Foresight
program
FX This research was supported by the BRL (Basic Research Laboratory)
program through the National Research Foundation of Korea funded by the
Ministry of Education, Science and Technology (2012-0000347) and by the
National Research Foundation of Korea (NRF) A3 Foresight program.
NR 37
TC 8
Z9 8
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1436-3291
EI 1436-3305
J9 GASTRIC CANCER
JI Gastric Cancer
PD JUL
PY 2015
VL 18
IS 3
BP 580
EP 589
DI 10.1007/s10120-014-0411-x
PG 10
WC Oncology; Gastroenterology & Hepatology
SC Oncology; Gastroenterology & Hepatology
GA CN3KL
UT WOS:000358325000015
PM 25091081
ER
PT J
AU Sheng, JT
Li, FH
Wong, STC
AF Sheng, Jianting
Li, Fuhai
Wong, Stephen T. C.
TI Optimal Drug Prediction From Personal Genomics Profiles
SO IEEE JOURNAL OF BIOMEDICAL AND HEALTH INFORMATICS
LA English
DT Article
DE Drug response prediction; drug sensitivity; personal genomics;
personalized medicine
ID GENE-EXPRESSION; EVEROLIMUS SENSITIVITY; CANCER; IDENTIFICATION;
DISCOVERY; NETWORK; TUMORS
AB Cancer patients often show heterogeneous drug responses such that only a small subset of patients is sensitive to a given anticancer drug. With the availability of large-scale genomic profiling via next-generation sequencing, it is now economically feasible to profile the whole transcriptome and genome of individual patients in order to identify their unique genetic mutations and differentially expressed genes, which are believed to be responsible for heterogeneous drug responses. Although subtyping analysis has identified patient subgroups sharing common biomarkers, there is no effective method to predict the drug response of individual patients precisely and reliably. Herein, we propose a novel computational algorithm to predict the drug response of individual patients based on personal genomic profiles, as well as pharmacogenomic and drug sensitivity data. Specifically, more than 600 cancer cell lines (viewed as individual patients) across over 50 types of cancers and their responses to 75 drugs were obtained from the genomics of drug sensitivity in cancer database. The drug-specific sensitivity signatures were determined from the changes in genomic profiles of individual cell lines in response to a specific drug. The optimal drugs for individual cell lines were predicted by integrating the votes from other cell lines. The experimental results show that the proposed drug prediction algorithm can be used to improve greatly the reliability of finding optimal drugs for individual patients and will, thus, form a key component in the precision medicine infrastructure for oncology care.
C1 [Sheng, Jianting] Weill Cornell Med Coll, NCI, Ctr Modeling Canc Dev, Dept Syst Med & Bioengn,Houston Methodist Res Ins, Houston, TX 77030 USA.
[Li, Fuhai; Wong, Stephen T. C.] Weill Cornell Med Coll, Houston Methodist Hosp, NCI, Ctr Modeling Canc Dev,Dept Syst Med & Bioengn,Hou, Houston, TX 77030 USA.
[Li, Fuhai; Wong, Stephen T. C.] Weill Cornell Med Coll, Houston Methodist Hosp, Houston Methodist Canc Ctr, Houston, TX 77030 USA.
RP Sheng, JT (reprint author), Weill Cornell Med Coll, NCI, Ctr Modeling Canc Dev, Dept Syst Med & Bioengn,Houston Methodist Res Ins, Houston, TX 77030 USA.
EM jsheng@houstonmethodist.org; fli@houstonmethodist.org;
stwong@houstonmethodist.org
FU CPRIT [RP110532, NIH U54 CA149196, RP140113]; John S Dunn Research
Foundation; Ting Tsung and Wei Fong Chao Foundation
FX This work was supported by CPRIT under Grant RP110532, Grant NIH U54
CA149196, Grant RP140113, John S Dunn Research Foundation, and Ting
Tsung and Wei Fong Chao Foundation. Authors Jianting Sheng and Fuhai Li
contributed equally to this work.
NR 31
TC 2
Z9 2
U1 1
U2 10
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 2168-2194
J9 IEEE J BIOMED HEALTH
JI IEEE J. Biomed. Health Inform.
PD JUL
PY 2015
VL 19
IS 4
BP 1264
EP 1270
DI 10.1109/JBHI.2015.2412522
PG 7
WC Computer Science, Information Systems; Computer Science,
Interdisciplinary Applications; Mathematical & Computational Biology;
Medical Informatics
SC Computer Science; Mathematical & Computational Biology; Medical
Informatics
GA CN7NE
UT WOS:000358620500009
PM 25781964
ER
PT J
AU Wei, CH
Leaman, R
Lu, ZY
AF Wei, Chih-Hsuan
Leaman, Robert
Lu, Zhiyong
TI SimConcept: A Hybrid Approach for Simplifying Composite Named Entities
in Biomedical Text
SO IEEE JOURNAL OF BIOMEDICAL AND HEALTH INFORMATICS
LA English
DT Article
DE bioNLP; coordination ellipsis; composite mentions; named entity
recognition; text mining
ID GENE NORMALIZATION; PROTEIN-TRANSPORT; BIOCREATIVE III; SIMPLIFICATION;
IDENTIFICATION; RECOGNITION; MENTIONS; CORPUS; MODEL; TASK
AB One particular challenge in biomedical named entity recognition (NER) and normalization is the identification and resolution of composite named entities, where a single span refers to more than one concept (e.g., BRCA1/2). Previous NER and normalization studies have either ignored composite mentions, used simple ad hoc rules, or only handled coordination ellipsis, making a robust approach for handling multitype composite mentions greatly needed. To this end, we propose a hybrid method integrating a machine-learning model with a pattern identification strategy to identify the individual components of each composite mention. Our method, which we have named SimConcept, is the first to systematically handle many types of composite mentions. The technique achieves high performance in identifying and resolving composite mentions for three key biological entities: genes (90.42% in F-measure), diseases (86.47% in F-measure), and chemicals (86.05% in F-measure). Furthermore, our results show that using our SimConcept method can subsequently improve the performance of gene and disease concept recognition and normalization. SimConcept is available for download at: http://www.ncbi.nlm.nih.gov/CBBresearch/Lu/Demo/SimConcept/
C1 [Wei, Chih-Hsuan] NIH, Bethesda, MD 20894 USA.
Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
RP Wei, CH (reprint author), NIH, Bethesda, MD 20894 USA.
EM chih-hsuan.wei@nih.gov; robert.leaman@nih.gov; zhiyong.lu@nih.gov
FU NIH Intramural Research Program, National Library of Medicine
FX This work was supported by the NIH Intramural Research Program, National
Library of Medicine. This paper [1] was presented at the 5th ACM
Conference on Bioinformatics, Computational Biology, and Health
Informatics, September 2014.
NR 49
TC 4
Z9 4
U1 1
U2 6
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 2168-2194
J9 IEEE J BIOMED HEALTH
JI IEEE J. Biomed. Health Inform.
PD JUL
PY 2015
VL 19
IS 4
BP 1385
EP 1391
DI 10.1109/JBHI.2015.2422651
PG 7
WC Computer Science, Information Systems; Computer Science,
Interdisciplinary Applications; Mathematical & Computational Biology;
Medical Informatics
SC Computer Science; Mathematical & Computational Biology; Medical
Informatics
GA CN7NE
UT WOS:000358620500024
PM 25879978
ER
PT J
AU Conley, BA
AF Conley, Barbara A.
TI Genomically Guided Cancer Treatments: From "Promising" to "Clinically
Useful"
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Editorial Material
C1 NCI, Canc Diag Program, Div Canc Treatment & Diag, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Conley, BA (reprint author), NCI, Canc Diag Program, Div Canc Treatment & Diag, NIH,US Dept Hlth & Human Serv, 9609 Med Ctr Dr,Room 4W426,MSC 9730, Bethesda, MD 20892 USA.
EM conleyba@mail.nih.gov
NR 6
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
EI 1460-2105
J9 JNCI-J NATL CANCER I
JI JNCI-J. Natl. Cancer Inst.
PD JUL
PY 2015
VL 107
IS 7
AR djv168
DI 10.1093/jnci/djv168
PG 2
WC Oncology
SC Oncology
GA CN9QC
UT WOS:000358782900020
ER
PT J
AU Kramer, BS
Elmore, JG
AF Kramer, Barnett S.
Elmore, Joann G.
TI Projecting the Benefits and Harms of Mammography Using Statistical
Models: Proof or Proofiness?
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Editorial Material
ID OVERDIAGNOSIS
C1 [Kramer, Barnett S.] NCI, Canc Prevent Div, Rockville, MD 20852 USA.
[Elmore, Joann G.] Univ Washington, Sch Med, Seattle, WA USA.
RP Kramer, BS (reprint author), NCI, Canc Prevent Div, 9609 Med Ctr Dr,Room 5E410, Rockville, MD 20852 USA.
EM kramerb@mail.nih.gov
NR 10
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
EI 1460-2105
J9 JNCI-J NATL CANCER I
JI JNCI-J. Natl. Cancer Inst.
PD JUL
PY 2015
VL 107
IS 7
AR djv145
DI 10.1093/jnci/djv145
PG 2
WC Oncology
SC Oncology
GA CN9QC
UT WOS:000358782900018
ER
PT J
AU Mirabello, L
Yeager, M
Mai, PL
Gastier-Foster, JM
Gorlick, R
Khanna, C
Patino-Garcia, A
Sierrasesumaga, L
Lecanda, F
Andrulis, IL
Wunder, JS
Gokgoz, N
Barkauskas, DA
Zhang, XJ
Vogt, A
Jones, K
Boland, JF
Chanock, SJ
Savage, SA
AF Mirabello, Lisa
Yeager, Meredith
Mai, Phuong L.
Gastier-Foster, Julie M.
Gorlick, Richard
Khanna, Chand
Patino-Garcia, Ana
Sierrasesumaga, Luis
Lecanda, Fernando
Andrulis, Irene L.
Wunder, Jay S.
Gokgoz, Nalan
Barkauskas, Donald A.
Zhang, Xijun
Vogt, Aurelie
Jones, Kristine
Boland, Joseph F.
Chanock, Stephen J.
Savage, Sharon A.
TI Germline TP53 Variants and Susceptibility to Osteosarcoma
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID TUMOR-SUPPRESSOR GENE; LI-FRAUMENI SYNDROME; BREAST-CANCER; P53
MUTATIONS; CHILDREN; FAMILY; RHABDOMYOSARCOMA; SURVEILLANCE; PATTERNS;
SURVIVAL
AB The etiologic contribution of germline genetic variation to sporadic osteosarcoma is not well understood. Osteosarcoma is a sentinel cancer of Li-Fraumeni syndrome (LFS), in which approximately 70% of families meeting the classic criteria have germline TP53 mutations. We sequenced TP53 exons in 765 osteosarcoma cases. Data were analyzed with chi(2) tests, logistic regression, and Cox proportional hazards regression models. We observed a high frequency of young osteosarcoma cases (age <30 years) carrying a known LFS- or likely LFS-associated mutation (3.8%) or rare exonic variant (5.7%) with an overall frequency of 9.5%, compared with none in case patients age 30 years and older (P < .001). This high TP53 mutation prevalence in young osteosarcoma cases is statistically significantly greater than the previously reported prevalence of 3% (P = .0024). We identified a novel association between a TP53 rare variant and metastasis at diagnosis of osteosarcoma (rs1800372, odds ratio = 4.27, 95% confidence interval = 1.2 to 15.5, P = .026). Genetic susceptibility to young onset osteosarcoma is distinct from older adult onset osteosarcoma, with a high frequency of LFS-associated and rare exonic TP53 variants.
C1 [Mirabello, Lisa; Mai, Phuong L.; Chanock, Stephen J.; Savage, Sharon A.] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20850 USA.
[Yeager, Meredith; Zhang, Xijun; Vogt, Aurelie; Jones, Kristine; Boland, Joseph F.] Frederick Natl Lab Canc Res, Canc Genom Res Lab, Leidos Biomed Res, Frederick, MD USA.
[Gastier-Foster, Julie M.] Nationwide Childrens Hosp, Columbus, OH USA.
[Gastier-Foster, Julie M.] Ohio State Univ, Dept Pathol & Pediat, Columbus, OH 43210 USA.
[Gorlick, Richard] Childrens Hosp Montefiore, Albert Einstein Coll Med, Bronx, NY USA.
[Khanna, Chand] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Patino-Garcia, Ana; Sierrasesumaga, Luis; Lecanda, Fernando] Univ Navarra, Dept Pediat, Univ Navarra Clin, E-31080 Pamplona, Spain.
[Andrulis, Irene L.; Wunder, Jay S.; Gokgoz, Nalan] Univ Toronto, Mt Sinai Hosp, Litwin Ctr Canc Genet, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada.
[Barkauskas, Donald A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
RP Mirabello, L (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 6E422, Bethesda, MD 20850 USA.
EM mirabellol@mail.nih.gov
RI Patino-Garcia, Ana/I-4299-2012; Savage, Sharon/B-9747-2015; Andrulis,
Irene/E-7267-2013
OI Savage, Sharon/0000-0001-6006-0740;
FU Division of Cancer Epidemiology and Genetics, National Cancer Institute,
National Institutes of Health; Children's Oncology Group from the
National Cancer Institute, National Institutes of Health, Bethesda, MD
[U10 CA180886-01, U24 CA114766]; WWWW (QuadW) Foundation, Inc.; Ontario
Cancer Research Network; Canadian Institutes of Health Research; Ontario
Research Fund; Canadian Foundation for Innovation
FX This study was funded by the intramural research program of the Division
of Cancer Epidemiology and Genetics, National Cancer Institute, National
Institutes of Health. Research is supported by the Chair's Grant U10
CA180886-01 and Human Specimen Banking Grant U24 CA114766 of the
Children's Oncology Group from the National Cancer Institute, National
Institutes of Health, Bethesda, MD. Additional support for research is
provided by a grant from the WWWW (QuadW) Foundation, Inc.
(www.QuadW.org) to the Children's Oncology Group. This work was
supported in part by grants to ILA and JSW from the Ontario Cancer
Research Network, Canadian Institutes of Health Research, the Ontario
Research Fund, and Canadian Foundation for Innovation.
NR 37
TC 2
Z9 2
U1 1
U2 7
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
EI 1460-2105
J9 JNCI-J NATL CANCER I
JI JNCI-J. Natl. Cancer Inst.
PD JUL
PY 2015
VL 107
IS 7
AR djv101
DI 10.1093/jnci/djv101
PG 4
WC Oncology
SC Oncology
GA CN9QC
UT WOS:000358782900007
ER
PT J
AU Sung, HN
Rosenberg, PS
Chen, WQ
Hartman, M
Lim, WY
Chia, KS
Mang, OWK
Chiang, CJ
Kang, D
Ngan, RKC
Tse, LA
Anderson, WF
Yang, XHR
AF Sung, Hyuna
Rosenberg, Philip S.
Chen, Wan-Qing
Hartman, Mikael
Lim, Wei-yen
Chia, Kee Seng
Mang, Oscar Wai-Kong
Chiang, Chun-Ju
Kang, Daehee
Ngan, Roger Kai-Cheong
Tse, Lap Ah
Anderson, William F.
Yang, Xiaohong R.
TI Female Breast Cancer Incidence Among Asian and Western Populations: More
Similar Than Expected
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID YOUNG-WOMEN; SCREENING SURVEY; AGE; TRENDS; PERIOD; RATES; MORTALITY;
TAIWAN; JAPAN; SURVEILLANCE
AB Background: Previous reports suggested that female breast cancer is associated with earlier ages at onset among Asian than Western populations. However, most studies utilized cross-sectional analyses that may be confounded by calendar-period and/or birth cohort effects. We, therefore, considered a longitudinal (forward-looking) approach adjusted for calendar-period changes and conditioned upon birth cohort.
Methods: Invasive female breast cancer data (1988-2009) were obtained from cancer registries in China, Hong Kong, South Korea, Taiwan, Singapore, and the United States. Age-period-cohort models were used to extrapolate longitudinal age-specific incidence rates for the 1920, 1944, and 1970 birth cohorts.
Results: Cross-sectional age-specific incidence rates rose continuously until age 80 years among US white women, but plateaued or decreased after age 50 years among Asian women. In contrast, longitudinal age-specific rates were proportional (similar) among all Asian countries and the United States with incidence rates rising continuously until age 80 years. The extrapolated estimates for the most recent cohorts in some Asian countries actually showed later ages at onset than in the United States. Additionally, over successive birth cohorts, the incidence rate ratios (IRRs) for the longitudinal curves converged (narrowed) between Asian and US white women.
Conclusions: Similar longitudinal age-specific incidence rates along with converging IRRs indicate that the age effects for invasive breast cancer are more similar among Asian and Western populations than might be expected from a solely cross-sectional analysis. Indeed, the Asian breast cancer rates in recent generations are even surpassing the historically high rates in the United States, highlighting an urgent need for efficient prevention and treatment strategies among Asian populations.
C1 [Sung, Hyuna; Rosenberg, Philip S.; Anderson, William F.; Yang, Xiaohong R.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Chen, Wan-Qing] Natl Off Canc Prevent & Control, Beijing, Peoples R China.
[Chen, Wan-Qing] Natl Canc Ctr, Natl Cent Canc Registry, Beijing, Peoples R China.
[Hartman, Mikael] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Hartman, Mikael; Lim, Wei-yen; Chia, Kee Seng] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore.
[Hartman, Mikael] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Surg, Singapore 117548, Singapore.
[Mang, Oscar Wai-Kong; Ngan, Roger Kai-Cheong] Hosp Author, Hong Kong Canc Registry, Hong Kong, Hong Kong, Peoples R China.
[Chiang, Chun-Ju] Natl Taiwan Univ, Coll Publ Hlth, Taiwan Canc Registry, Taipei 10764, Taiwan.
[Chiang, Chun-Ju] Natl Taiwan Univ, Coll Publ Hlth, Grad Inst Epidemiol & Prevent Med, Taipei 10764, Taiwan.
[Kang, Daehee] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea.
[Ngan, Roger Kai-Cheong] Queen Elizabeth Hosp, Dept Clin Oncol, Kowloon, Hong Kong, Peoples R China.
[Tse, Lap Ah] Chinese Univ Hong Kong, JC Sch Publ Hlth & Primary Care, Div Occupat & Environm Hlth, Hong Kong, Hong Kong, Peoples R China.
RP Sung, H (reprint author), NCI, NIH, DCEG, GEB, 9609 Med Ctr Dr,6E512, Bethesda, MD 20892 USA.
EM hyuna.sung@nih.gov
RI Hartman, Mikael/B-4324-2011
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Division of Cancer Epidemiology and Genetics
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Division of
Cancer Epidemiology and Genetics.
NR 40
TC 4
Z9 4
U1 0
U2 7
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
EI 1460-2105
J9 JNCI-J NATL CANCER I
JI JNCI-J. Natl. Cancer Inst.
PD JUL
PY 2015
VL 107
IS 7
AR djv107
DI 10.1093/jnci/djv107
PG 7
WC Oncology
SC Oncology
GA CN9QC
UT WOS:000358782900010
ER
PT J
AU Weinberg, CR
Zaykin, D
AF Weinberg, C. R.
Zaykin, D.
TI Is Bad Luck the Main Cause of Cancer?
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Editorial Material
ID RISK
AB A recent study reports that the log lifetime incidence rate across a selection of 31 cancer types is highly correlated with the log of the estimated tissue-specific lifetime number of stem cell divisions. This observation, which underscores the importance of errors in DNA replication, has been viewed as implying that most cancers arise through unavoidable bad luck, leading to the suggestion that research efforts should focus on early detection, rather than etiology or prevention. We argue that three statistical issues can, if ignored, lead analysts to incorrect conclusions. Statistics for traffic fatalities across the United States provide an example to demonstrate those inferential pitfalls. While the contribution of random cellular events to disease is often underappreciated, the role of chance is necessarily difficult to quantify. The conclusion that most cases of cancer are fundamentally unpreventable because they are the result of chance is unwarranted.
C1 [Weinberg, C. R.; Zaykin, D.] NIEHS, Biostat & Computat Biol Branch, Res Triangle Pk, NC 27709 USA.
RP Weinberg, CR (reprint author), NIEHS, Biostat & Computat Biol Branch, MD A3-03,POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM weinber2@niehs.nih.gov
NR 10
TC 6
Z9 6
U1 2
U2 14
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
EI 1460-2105
J9 JNCI-J NATL CANCER I
JI JNCI-J. Natl. Cancer Inst.
PD JUL
PY 2015
VL 107
IS 7
AR djv125
DI 10.1093/jnci/djv125
PG 4
WC Oncology
SC Oncology
GA CN9QC
UT WOS:000358782900015
ER
PT J
AU Prins, P
de Ligt, J
Tarasov, A
Jansen, RC
Cuppen, E
Bourne, PE
AF Prins, Pjotr
de Ligt, Joep
Tarasov, Artem
Jansen, Ritsert C.
Cuppen, Edwin
Bourne, Philip E.
TI Toward effective software solutions for big biology
SO NATURE BIOTECHNOLOGY
LA English
DT Letter
C1 [Prins, Pjotr; Cuppen, Edwin] Univ Med Ctr, Dept Med Genet, Utrecht, Netherlands.
[Prins, Pjotr; de Ligt, Joep; Cuppen, Edwin] Royal Netherlands Acad Arts & Sci KNAW, Hubrecht Inst, CancerGenom, Utrecht, Netherlands.
[Prins, Pjotr] Wageningen Univ, Dept Nematol, NL-6700 AP Wageningen, Netherlands.
[Tarasov, Artem] St Petersburg State Univ, St Petersburg 199034, Russia.
[Jansen, Ritsert C.] Univ Groningen, Groningen Bioinformat Ctr, Groningen, Netherlands.
[Bourne, Philip E.] NIH, Bethesda, MD 20892 USA.
RP Prins, P (reprint author), Univ Med Ctr, Dept Med Genet, Utrecht, Netherlands.
EM j.c.p.prins@umcutrecht.nl
RI Cuppen, Edwin/H-2389-2016;
OI Cuppen, Edwin/0000-0002-0400-9542; Prins, Pjotr/0000-0002-8021-9162; de
Ligt, Joep/0000-0002-0348-419X
NR 5
TC 4
Z9 4
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1087-0156
EI 1546-1696
J9 NAT BIOTECHNOL
JI Nat. Biotechnol.
PD JUL
PY 2015
VL 33
IS 7
BP 686
EP 687
PG 2
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA CN4JJ
UT WOS:000358396100016
PM 26154002
ER
PT J
AU Gargis, AS
Kalman, L
Bick, DP
da Silva, C
Dimmock, DP
Funke, BH
Gowrisankar, S
Hegde, MR
Kulkarni, S
Mason, CE
Nagarajan, R
Voelkerding, KV
Worthey, EA
Aziz, N
Barnes, J
Bennett, SF
Bisht, H
Church, DM
Dimitrova, Z
Gargis, SR
Hafez, N
Hambuch, T
Hyland, FCL
Luna, RA
MacCannell, D
Mann, T
McCluskey, MR
McDaniel, TK
Ganova-Raeval, LM
Rehm, HL
Reid, J
Campo, DS
Resnick, RB
Ridge, PG
Salit, ML
Skums, P
Wong, LJC
Zehnbauer, BA
Zook, JM
Lubin, IM
AF Gargis, Amy S.
Kalman, Lisa
Bick, David P.
da Silva, Cristina
Dimmock, David P.
Funke, Birgit H.
Gowrisankar, Sivakumar
Hegde, Madhuri R.
Kulkarni, Shashikant
Mason, Christopher E.
Nagarajan, Rakesh
Voelkerding, Karl V.
Worthey, Elizabeth A.
Aziz, Nazneen
Barnes, John
Bennett, Sarah F.
Bisht, Himani
Church, Deanna M.
Dimitrova, Zoya
Gargis, Shaw R.
Hafez, Nabil
Hambuch, Tina
Hyland, Fiona C. L.
Luna, Ruth Ann
MacCannell, Duncan
Mann, Tobias
McCluskey, Megan R.
McDaniel, Timothy K.
Ganova-Raeval, Lilia M.
Rehm, Heidi L.
Reid, Jeffrey
Campo, David S.
Resnick, Richard B.
Ridge, Perry G.
Salit, Marc L.
Skums, Pavel
Wong, Lee-Jun C.
Zehnbauer, Barbara A.
Zook, Justin M.
Lubin, Ira M.
TI Good laboratory practice for clinical next-generation sequencing
informatics pipelines
SO NATURE BIOTECHNOLOGY
LA English
DT Letter
ID ACMG RECOMMENDATIONS; INCIDENTAL FINDINGS; STANDARDS
C1 [Gargis, Amy S.; Kalman, Lisa; Zehnbauer, Barbara A.; Lubin, Ira M.] Ctr Dis Control & Prevent, Div Lab Syst, Atlanta, GA USA.
[Bick, David P.; Dimmock, David P.; Worthey, Elizabeth A.] Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA.
[da Silva, Cristina; Hegde, Madhuri R.] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA USA.
[Funke, Birgit H.; Gowrisankar, Sivakumar; Rehm, Heidi L.] Partners Healthcare Personalized Med, Lab Mol Med, Cambridge, MA USA.
[Funke, Birgit H.; Gowrisankar, Sivakumar; Rehm, Heidi L.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA.
[Kulkarni, Shashikant] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA.
[Kulkarni, Shashikant] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA.
[Kulkarni, Shashikant; Nagarajan, Rakesh] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA.
[Mason, Christopher E.] Cornell Univ, Dept Physiol & Biophys, New York, NY 10021 USA.
[Voelkerding, Karl V.; Ridge, Perry G.] Univ Utah, Dept Pathol, Salt Lake City, UT USA.
[Voelkerding, Karl V.] Associated Reg & Univ Pathologists ARUP Labs, Inst Clin & Expt Pathol, Salt Lake City, UT USA.
[Aziz, Nazneen] Coll Amer Pathologists, Northfield, IL USA.
[Barnes, John] Ctr Dis Control & Prevent, Natl Ctr Immunizat & Resp Dis, Atlanta, GA USA.
[Bennett, Sarah F.] Ctr Medicare & Medicaid Serv, Div Lab Serv, Baltimore, MD USA.
[Bisht, Himani] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
[Church, Deanna M.] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA.
[Dimitrova, Zoya; Ganova-Raeval, Lilia M.; Campo, David S.] Ctr Dis Control & Prevent, Div Viral Hepatitis, Atlanta, GA USA.
[Gargis, Shaw R.] Ctr Dis Control & Prevent, Div Select Agents & Toxins, Atlanta, GA USA.
[Hafez, Nabil; Resnick, Richard B.; Skums, Pavel] GenomeQuest, Westborough, MA USA.
[Hambuch, Tina] Illumina, Clin Serv, San Diego, CA USA.
[Hyland, Fiona C. L.] Thermo Fisher Sci, San Francisco, CA USA.
[Luna, Ruth Ann] Texas Childrens Hosp, Texas Childrens Microbiome Ctr, Houston, TX USA.
[Luna, Ruth Ann] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA.
[MacCannell, Duncan] Ctr Dis Control & Prevent, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA USA.
[Mann, Tobias] Illumina, San Diego, CA USA.
[McCluskey, Megan R.] SoftGenetics, State Coll, State Coll, PA USA.
[McDaniel, Timothy K.; Wong, Lee-Jun C.] Illumina, Oncol, San Diego, CA USA.
[Reid, Jeffrey] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Salit, Marc L.; Zook, Justin M.] NIST, Mat Measurement Lab, Gaithersburg, MD 20899 USA.
RP Gargis, AS (reprint author), Ctr Dis Control & Prevent, Div Preparedness & Emerging Infect, Atlanta, GA 30322 USA.
RI Zook, Justin/B-7000-2008
OI Zook, Justin/0000-0003-2309-8402
FU NHGRI NIH HHS [U01HG006500, U41HG006834]
NR 11
TC 26
Z9 28
U1 2
U2 12
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1087-0156
EI 1546-1696
J9 NAT BIOTECHNOL
JI Nat. Biotechnol.
PD JUL
PY 2015
VL 33
IS 7
BP 689
EP 693
DI 10.1038/nbt.3237
PG 5
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA CN4JJ
UT WOS:000358396100018
PM 26154004
ER
PT J
AU Castillo, JP
Rui, H
Basilio, D
Das, A
Roux, B
Latorre, R
Bezanilla, F
Holmgren, M
AF Castillo, Juan P.
Rui, Huan
Basilio, Daniel
Das, Avisek
Roux, Benoit
Latorre, Ramon
Bezanilla, Francisco
Holmgren, Miguel
TI Mechanism of potassium ion uptake by the Na+/K+-ATPase
SO NATURE COMMUNICATIONS
LA English
DT Article
ID MOLECULAR-DYNAMICS SIMULATIONS; CURRENT-VOLTAGE RELATIONSHIP;
CRYSTAL-STRUCTURE; CHARGE TRANSLOCATION; PUMP CURRENT; NA,K PUMP; NA/K
PUMP; CALCIUM-PUMP; PK(A) VALUES; EXTRACELLULAR ACCESS
AB The Na+/ K+-ATPase restores sodium (Na+) and potassium (K+) electrochemical gradients dissipated by action potentials and ion-coupled transport processes. As ions are transported, they become transiently trapped between intracellular and extracellular gates. Once the external gate opens, three Na+ ions are released, followed by the binding and occlusion of two K+ ions. While the mechanisms of Na+ release have been well characterized by the study of transient Na+ currents, smaller and faster transient currents mediated by external K+ have been more difficult to study. Here we show that external K+ ions travelling to their binding sites sense only a small fraction of the electric field as they rapidly and simultaneously become occluded. Consistent with these results, molecular dynamics simulations of a pump model show a wide water-filled access channel connecting the binding site to the external solution. These results suggest a mechanism of K+ gating different from that of Na+ occlusion.
C1 Univ Chile, Fac Ciencias, Lab Fisiol Celular, Montemar 254006, Chile.
[Castillo, Juan P.; Latorre, Ramon] Univ Valparaiso, Ctr Interdisciplinario Neurociencia Valparaiso, Valparaiso 2366103, Chile.
[Rui, Huan; Das, Avisek; Roux, Benoit; Bezanilla, Francisco] Univ Chicago, Gordon Ctr Integrat Sci, Dept Biochem & Mol Biol, Chicago, IL 60637 USA.
[Basilio, Daniel] Univ Chile, Fac Ciencias, Santiago 7800003, Chile.
[Holmgren, Miguel] NINDS, Gordon Neurophysiol Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Latorre, R (reprint author), Univ Chile, Fac Ciencias, Lab Fisiol Celular, Montemar 254006, Chile.
EM ramon.latorre@uv.cl; fbezanilla@peds.bsd.uchicago.edu;
holmgren@ninds.nih.gov
RI Basilio, Daniel/A-9350-2009
OI Basilio, Daniel/0000-0002-5346-8921
FU Fogarty International Research Collaboration Award [RO3 TW008351]; NIH
[R01-GM062342, R01-GM030376, U54-GM087519]; FONDECYT [1110430, 1150273];
Millennium Scientific Initiative of the Chilean Ministry of Economy,
Development and Tourism; NIH (NINDS); National Institutes of Health
[P41GM103712-S1]; Pittsburgh Supercomputing Center (PSC)
FX This work was supported by a Fogarty International Research
Collaboration Award grant (RO3 TW008351) to R.L., F.B. and M.H. Further
support was obtained from NIH grants R01-GM062342 (B.R.), R01-GM030376
(F.B.) and U54-GM087519 (F.B., B.R. and M.H.). R.L. was supported by
FONDECYT grant 1110430 and 1150273. The Centro Interdisciplinario de
Neurociencia de Valparaiso (CINV) is a Millennium Institute supported by
the Millennium Scientific Initiative of the Chilean Ministry of Economy,
Development and Tourism. M.H. is supported by the Intramural Research
Program of the NIH (NINDS). We thank the Section on Instrumentation of
the National Institute of Mental Health for technical assistance. We
thank Alan Neely, Ana Maria Navia, Rodrigo Toro and David Parada for in
situ Montemar logistics and David Gadsby and Paul De Weer for
participating in preliminary experiments performed in Woods Hole, MA.
Anton computer time was provided by the National Center for Multiscale
Modeling of Biological Systems (MMBioS) through Grant P41GM103712-S1
from the National Institutes of Health and the Pittsburgh Supercomputing
Center (PSC). The Anton machine at PSC was generously made available by
D.E. Shaw Research.
NR 69
TC 6
Z9 6
U1 10
U2 36
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD JUL
PY 2015
VL 6
AR 7622
DI 10.1038/ncomms8622
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CO0QM
UT WOS:000358857000015
PM 26205423
ER
PT J
AU Krumm, BE
White, JF
Shah, P
Grisshammer, R
AF Krumm, Brian E.
White, Jim F.
Shah, Priyanka
Grisshammer, Reinhard
TI Structural prerequisites for G-protein activation by the neurotensin
receptor
SO NATURE COMMUNICATIONS
LA English
DT Article
ID RESOLUTION CRYSTAL-STRUCTURE; COUPLED RECEPTOR; MEMBRANE-PROTEINS;
FUNCTIONAL EXPRESSION; DIRECTED EVOLUTION; ACTIVE STATE; STABILITY;
RHODOPSIN; GPCR; THERMOSTABILIZATION
AB We previously determined the structure of neurotensin receptor NTSR1 in an active-like conformation with six thermostabilizing mutations bound to the peptide agonist neurotensin. This receptor was unable to activate G proteins, indicating that the mutations restricted NTSR1 to relate agonist binding to G-protein activation. Here we analyse the effect of three of those mutations (E166A(3.49), L310A(6.37), F358A(7.42)) and present two structures of NTSR1 able to catalyse nucleotide exchange at G alpha. The presence of F358(7.42) causes the conserved W321(6.48) to adopt a side chain orientation parallel to the lipid bilayer sealing the collapsed Na+ ion pocket and linking the agonist with residues in the lower receptor part implicated in GPCR activation. In the intracellular receptor half, the bulkier L310(6.37) side chain dictates the position of R167(3.50) of the highly conserved D/ERY motif. These residues, together with the presence of E166(3.49) provide determinants for G-protein activation by NTSR1.
C1 [Krumm, Brian E.; White, Jim F.; Shah, Priyanka; Grisshammer, Reinhard] NINDS, Membrane Prot Struct Funct Unit, NIH, US Dept HHS, Rockville, MD 20852 USA.
RP Grisshammer, R (reprint author), NINDS, Membrane Prot Struct Funct Unit, NIH, US Dept HHS, 5625 Fishers Lane, Rockville, MD 20852 USA.
EM rkgriss@helix.nih.gov
FU National Institutes of Health, National Institute of Neurological
Disorders and Stroke; National Cancer Institute [ACB-12002]; National
Institute of General Medical Sciences [AGM-12006]; DOE Office of Science
[DE-AC02-06CH11357]; U.S. Department of Energy, Office of Science,
Office of Basic Energy Sciences [DE-AC02-76SF00515]; GM/CA at APS; DOE
Office of Biological and Environmental Research; National Institutes of
Health, National Institute of General Medical Sciences [P41GM103393]
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Neurological
Disorders and Stroke. We thank the staff at the General Medicine and
Cancer Institute's Collaborative Access Team (GM/CA-CAT) beamline at the
Advanced Photon Source, Argonne National Laboratory; and personnel at
the Stanford Synchrotron Radiation Lightsource, beamline 12-2, for their
assistance during data acquisition. GM/CA at APS has been funded in
whole or in part with Federal funds from the National Cancer Institute
(ACB-12002) and the National Institute of General Medical Sciences
(AGM-12006). This research used resources of the Advanced Photon Source,
a U.S. Department of Energy (DOE) Office of Science User Facility
operated for the DOE Office of Science by Argonne National Laboratory
under Contract No. DE-AC02-06CH11357. Use of the Stanford Synchrotron
Radiation Lightsource, SLAC National Accelerator Laboratory, is
supported by the U.S. Department of Energy, Office of Science, Office of
Basic Energy Sciences under Contract No. DE-AC02-76SF00515. The SSRL
Structural Molecular Biology Program is supported by the DOE Office of
Biological and Environmental Research and by the National Institutes of
Health, National Institute of General Medical Sciences (including
P41GM103393). The production of NTSR1 baculoviruses was done at the
Protein Expression Laboratory, Leidos, National Cancer Institute,
Frederick, MD, USA. DNA sequence analysis was performed in part by the
National Institute of Neurological Disorders and Stroke DNA Sequencing
Facility. Peptides were synthesized at the Center for Biologics
Evaluation and Research (Food and Drug Administration, Bethesda, MD,
USA). We thank Di Xia (Center for Cancer Research, NCI) for review of
the X-ray data and coordinates.
NR 55
TC 12
Z9 13
U1 1
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD JUL
PY 2015
VL 6
AR 7895
DI 10.1038/ncomms8895
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CO0SK
UT WOS:000358862400001
PM 26205105
ER
PT J
AU Schumacher, FR
Schmit, SL
Jiao, S
Edlund, CK
Wang, HS
Zhang, B
Hsu, L
Huang, SC
Fischer, CP
Harju, JF
Idos, GE
Lejbkowicz, F
Manion, FJ
McDonnell, K
McNeil, CE
Melas, M
Rennert, HS
Shi, W
Thomas, DC
Van Den Berg, DJ
Hutter, CM
Aragaki, AK
Butterbach, K
Caan, BJ
Carlson, CS
Chanock, SJ
Curtis, KR
Fuchs, CS
Gala, M
Giocannucci, EL
Gogarten, SM
Hayes, RB
Henderson, B
Hunter, DJ
Jackson, RD
Kolonel, LN
Kooperberg, C
Kury, S
LaCroix, A
Laurie, CC
Laurie, CA
Lemire, M
Levine, D
Ma, J
Makar, KW
Qu, CH
Taverna, D
Ulrich, CM
Wu, KN
Kono, S
West, DW
Berndt, SI
Bezieau, S
Brenner, H
Campbell, PT
Chan, AT
Chang-Claude, J
Coetzee, GA
Conti, DV
Duggan, D
Figueiredo, JC
Fortini, BK
Gallinger, SJ
Gauderman, WJ
Giles, G
Green, R
Haile, R
Harrison, TA
Hoffmeister, M
Hopper, JL
Hudson, TJ
Jacobs, E
Iwasaki, M
Jee, SH
Jenkins, M
Jia, WH
Joshi, A
Li, L
Lindor, NM
Matsuo, K
Moreno, V
Mukherjee, B
Newcomb, PA
Potter, JD
Raskin, L
Rennert, G
Rosse, S
Severi, G
Schoen, RE
Seminara, D
Shu, XO
Slattery, ML
Tsugane, S
White, E
Xiang, YB
Zanke, BW
Zheng, W
Le Marchand, L
Casey, G
Gruber, SB
Peters, U
AF Schumacher, Fredrick R.
Schmit, Stephanie L.
Jiao, Shuo
Edlund, Christopher K.
Wang, Hansong
Zhang, Ben
Hsu, Li
Huang, Shu-Chen
Fischer, Christopher P.
Harju, John F.
Idos, Gregory E.
Lejbkowicz, Flavio
Manion, Frank J.
McDonnell, Kevin
McNeil, Caroline E.
Melas, Marilena
Rennert, Hedy S.
Shi, Wei
Thomas, Duncan C.
Van Den Berg, David J.
Hutter, Carolyn M.
Aragaki, Aaron K.
Butterbach, Katja
Caan, Bette J.
Carlson, Christopher S.
Chanock, Stephen J.
Curtis, Keith R.
Fuchs, Charles S.
Gala, Manish
Giocannucci, Edward L.
Gogarten, Stephanie M.
Hayes, Richard B.
Henderson, Brian
Hunter, David J.
Jackson, Rebecca D.
Kolonel, Laurence N.
Kooperberg, Charles
Kury, Sebastian
LaCroix, Andrea
Laurie, Cathy C.
Laurie, Cecelia A.
Lemire, Mathiew
Levine, David
Ma, Jing
Makar, Karen W.
Qu, Conghui
Taverna, Darin
Ulrich, Cornelia M.
Wu, Kana
Kono, Suminori
West, Dee W.
Berndt, Sonja I.
Bezieau, Stephane
Brenner, Hermann
Campbell, Peter T.
Chan, Andrew T.
Chang-Claude, Jenny
Coetzee, Gerhard A.
Conti, David V.
Duggan, David
Figueiredo, Jane C.
Fortini, Barbara K.
Gallinger, Steven J.
Gauderman, W. James
Giles, Graham
Green, Roger
Haile, Robert
Harrison, Tabitha A.
Hoffmeister, Michael
Hopper, John L.
Hudson, Thomas J.
Jacobs, Eric
Iwasaki, Motoki
Jee, Sun Ha
Jenkins, Mark
Jia, Wei-Hua
Joshi, Amit
Li, Li
Lindor, Noralene M.
Matsuo, Keitaro
Moreno, Victor
Mukherjee, Bhramar
Newcomb, Polly A.
Potter, John D.
Raskin, Leon
Rennert, Gad
Rosse, Stephanie
Severi, Gianluca
Schoen, Robert E.
Seminara, Daniela
Shu, Xiao-Ou
Slattery, Martha L.
Tsugane, Shoichiro
White, Emily
Xiang, Yong-Bing
Zanke, Brent W.
Zheng, Wei
Le Marchand, Loic
Casey, Graham
Gruber, Stephen B.
Peters, Ulrike
TI Genome-wide association study of colorectal cancer identifies six new
susceptibility loci
SO NATURE COMMUNICATIONS
LA English
DT Article
ID NEGATIVE REGULATOR LRIG1; GENOTYPE IMPUTATION; PANCREATIC-CANCER; RISK
LOCUS; METAANALYSIS; SCAN; 8Q24; CARCINOMA; VARIANTS; RECEPTOR
AB Genetic susceptibility to colorectal cancer is caused by rare pathogenic mutations and common genetic variants that contribute to familial risk. Here we report the results of a two-stage association study with 18,299 cases of colorectal cancer and 19,656 controls, with follow-up of the most statistically significant genetic loci in 4,725 cases and 9,969 controls from two Asian consortia. We describe six new susceptibility loci reaching a genome-wide threshold of P<5.0E - 08. These findings provide additional insight into the underlying biological mechanisms of colorectal cancer and demonstrate the scientific value of large consortia-based genetic epidemiology studies.
C1 [Schumacher, Fredrick R.; Schmit, Stephanie L.; Edlund, Christopher K.; Huang, Shu-Chen; Idos, Gregory E.; McDonnell, Kevin; McNeil, Caroline E.; Melas, Marilena; Thomas, Duncan C.; Van Den Berg, David J.; Henderson, Brian; Coetzee, Gerhard A.; Conti, David V.; Figueiredo, Jane C.; Fortini, Barbara K.; Gauderman, W. James; Raskin, Leon; Rennert, Gad; Casey, Graham; Gruber, Stephen B.] Univ So Calif, Keck Sch Med, USC Norris Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90089 USA.
[Schmit, Stephanie L.; Gruber, Stephen B.] Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA 90089 USA.
[Jiao, Shuo; Hsu, Li; Aragaki, Aaron K.; Carlson, Christopher S.; Curtis, Keith R.; Kooperberg, Charles; LaCroix, Andrea; Makar, Karen W.; Qu, Conghui; Ulrich, Cornelia M.; Harrison, Tabitha A.; Rosse, Stephanie; White, Emily; Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98124 USA.
[Wang, Hansong; Le Marchand, Loic] Univ Hawaii Canc Ctr, Program Epidemiol, Honolulu, HI 96822 USA.
[Zhang, Ben] Third Mil Med Univ, Southwest Hosp, Dept Gen Surg, Chongqing 400038, Peoples R China.
[Fischer, Christopher P.; Harju, John F.; Manion, Frank J.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48105 USA.
[Lejbkowicz, Flavio; Rennert, Hedy S.; Rennert, Gad] Carmel Hosp, Dept Community Med & Epidemiol, IL-34361 Haifa, Israel.
[Lejbkowicz, Flavio; Rennert, Hedy S.; Rennert, Gad] Clalit Hlth Serv Natl Canc Control Ctr, IL-34361 Haifa, Israel.
[Shi, Wei] Childrens Hosp, Dept Surg, Los Angeles, CA 90027 USA.
[Hutter, Carolyn M.] NCI, Div Canc Control & Populat Sci, NIH, Rockville, MD 20892 USA.
[Butterbach, Katja; Brenner, Hermann; Hoffmeister, Michael] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, D-69121 Heidelberg, Germany.
[Caan, Bette J.] Kaiser Permanente Med Care Program Northern Calif, Div Res, Oakland, CA 94612 USA.
[Chanock, Stephen J.; Berndt, Sonja I.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Brookline, MA 02115 USA.
[Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Brookline, MA 02115 USA.
[Gala, Manish; Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
[Giocannucci, Edward L.; Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Giocannucci, Edward L.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA.
[Gogarten, Stephanie M.; Laurie, Cathy C.; Laurie, Cecelia A.; Levine, David] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Hayes, Richard B.] NYU, Sch Med, Dept Populat Hlth, Div Epidemiol, New York, NY 10016 USA.
[Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Genet Epidemiol & Stat Genet, Boston, MA 02115 USA.
[Jackson, Rebecca D.] Ohio State Univ, Dept Med, Columbus, OH 43210 USA.
[Kolonel, Laurence N.] Univ Hawaii Manoa, Off Publ Hlth Studies, Honolulu, HI 96822 USA.
[Kury, Sebastian] CHU Nantes, Serv Genet Med, F-44093 Nantes, France.
[Lemire, Mathiew] Ontario Inst Canc Res, Toronto, ON M5G 0A3, Canada.
[Ma, Jing] Harvard Univ, Sch Publ Hlth, Boston, MA 02114 USA.
[Taverna, Darin] Phoenix Coll, Phoenix, AZ 85013 USA.
[Ulrich, Cornelia M.] German Canc Res Ctr, Div Prevent Oncol, D-69120 Heidelberg, Germany.
[Ulrich, Cornelia M.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
[Wu, Kana] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Kono, Suminori; Matsuo, Keitaro] Kyushu Univ, Dept Prevent Med, Fukuoka 8128582, Japan.
[West, Dee W.] Inst Publ Hlth, Canc Registry Greater Calif, Sacramento, CA 95825 USA.
[Bezieau, Stephane] Ctr Hosp Univ Hotel Dieu, F-44093 Nantes, France.
[Campbell, Peter T.; Jacobs, Eric] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, Unit Genet Epidemiol, D-69121 Heidelberg, Germany.
[Conti, David V.] Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90089 USA.
[Duggan, David] Translat Genom Res Inst, Genet Basis Human Dis Div, Phoenix, AZ 85004 USA.
[Gallinger, Steven J.] Mt Sinai Hosp, Zane Cohen Ctr Digest Dis, Toronto, ON M5T 3L9, Canada.
[Giles, Graham; Severi, Gianluca] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic 3004, Australia.
[Green, Roger] Mem Univ Newfoundland, Discipline Genet, St John, NF A1B 3V6, Canada.
[Haile, Robert] Stanford Univ, Dept Med, Div Oncol, Stanford, CA 94305 USA.
[Hopper, John L.] Univ Melbourne, Ctr MEGA Epidemiol, Carlton, Vic 3010, Australia.
[Hudson, Thomas J.] Ontario Inst Canc Res, Dept Genom, Toronto, ON M5G 0A3, Canada.
[Iwasaki, Motoki; Tsugane, Shoichiro] Natl Canc Ctr, Res Ctr Canc Prevent & Screening, Tokyo 1040045, Japan.
[Jee, Sun Ha] Yonsei Univ, Grad Sch Publ Hlth, Dept Epidemiol & Hlth Promot, Seoul 120749, South Korea.
[Jenkins, Mark] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Biostat & Epidemiol, Parkville, Vic 3010, Australia.
[Jia, Wei-Hua] Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol South China, Guangzhou 510060, Guangdong, Peoples R China.
[Joshi, Amit] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Li, Li] Case Western Reserve Univ, Dept Family Med & Community Hlth, Cleveland, OH 44106 USA.
[Lindor, Noralene M.] Mayo Clin, Dept Hlth Sci Res, Scottsdale, AZ 85259 USA.
[Moreno, Victor] IDIBELL, Catalan Inst Oncol, Canc Epidemiol Serv, Barcelona 08908, Spain.
[Mukherjee, Bhramar] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
[Newcomb, Polly A.; Potter, John D.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Canc Prevent Program, Seattle, WA 98109 USA.
[Raskin, Leon; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Div Epidemiol, Nashville, TN 37203 USA.
[Raskin, Leon; Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN 37203 USA.
[Rennert, Gad] Technion Israel Inst Technol, Bruce Rappaport Fac Med, IL-3200003 Haifa, Israel.
[Severi, Gianluca] HuGeF, I-10126 Turin, Italy.
[Schoen, Robert E.] Univ Pittsburgh, Med Ctr, Dept Internal Med, Pittsburgh, PA 15213 USA.
[Seminara, Daniela] NCI, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA.
[Shu, Xiao-Ou] Vanderbilt Univ, Sch Med, Div Epidemiol, Nashville, TN 37203 USA.
[Slattery, Martha L.] Univ Utah, Hlth Sci Ctr, Dept Internal Med, Salt Lake City, UT 84132 USA.
[Xiang, Yong-Bing] Shanghai Canc Inst, Dept Epidemiol, Shanghai 220025, Peoples R China.
[Zanke, Brent W.] Univ Ottawa, Ottawa, ON K1N 6N5, Canada.
[Zanke, Brent W.] Ottawa Hosp Res Inst, Clin Epidemiol Program, Ottawa, ON K1Y 4E9, Canada.
RP Gruber, SB (reprint author), Univ So Calif, Keck Sch Med, USC Norris Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90089 USA.
EM sgruber@usc.edu
RI Hoffmeister, Michael/B-5745-2012; Bezieau, stephane/G-5621-2015; Raskin,
Leon/P-5765-2015; Jenkins, Mark/P-7803-2015; U-ID, Kyushu/C-5291-2016;
Gallinger, Steven/E-4575-2013; Brenner, Hermann/B-4627-2017;
OI Hoffmeister, Michael/0000-0002-8307-3197; KURY,
Sebastien/0000-0001-5497-0465; Potter, John/0000-0001-5439-1500;
Bezieau, stephane/0000-0003-0095-1319; Raskin, Leon/0000-0003-1195-7214;
Jenkins, Mark/0000-0002-8964-6160; Gogarten,
Stephanie/0000-0002-7231-9745; Hayes, Richard/0000-0002-0918-661X;
Moreno, Victor/0000-0002-2818-5487; Brenner,
Hermann/0000-0002-6129-1572; Giles, Graham/0000-0003-4946-9099
FU National Cancer Institute, National Institutes of Health under RFA
[CA-09-002, NIH/NCI U19 CA148107]
FX CORECT: this work was supported by the National Cancer Institute,
National Institutes of Health under RFA # CA-09-002, NIH/NCI U19
CA148107. The content of this manuscript does not necessarily reflect
the views or policies of the National Cancer Institute or any of the
collaborating centres in the CORECT consortium, nor does mention of
trade names, commercial products or organizations imply endorsement by
the US Government or the CORECT Consortium. ASTERISK: we are very
grateful to Dr Bruno Buecher without whom this project would not have
existed. We also thank all those who agreed to participate in this
study, including the patients and the healthy control persons, as well
as all the physicians, technicians and students. DACHS: we thank all
participants and cooperating clinicians, and Ute Handte-Daub, Renate
Hettler-Jensen, Utz Benscheid, Muhabbet Celik and Ursula Eilber for
excellent technical assistance. GECCO: we thank all those at the GECCO
Coordinating Center for helping bring together the data and people that
made this project possible. HPFS, NHS and PHS: we acknowledge Patrice
Soule and Hardeep Ranu of the Dana-Farber Harvard Cancer Center
High-Throughput Polymorphism Core who assisted in the genotyping for
NHS, HPFS and PHS under the supervision of Dr Immaculata Devivo and Dr
David Hunter, Qin (Carolyn) Guo and Lixue Zhu who assisted in
programming for NHS and HPFS and Haiyan Zhang who assisted in
programming for the PHS. We thank the participants and staff of the
Nurses' Health Study and the Health Professionals Follow-Up 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. We assume full responsibility for analyses and interpretation of
these data. PLCO: we thank Drs Christine Berg and Philip Prorok,
Division of Cancer Prevention, National Cancer Institute, the Screening
Center investigators and staff or the Prostate, Lung, Colorectal and
Ovarian (PLCO) Cancer Screening Trial, Mr. Tom Riley and staff,
Information Management Services Inc., Ms Barbara O'Brien and staff,
Westat Inc. and Drs Bill Kopp, Wen Shao and staff, SAIC-Frederick. Most
importantly, we acknowledge the study participants for their
contributions for making this study possible. The statements contained
herein are solely those of the authors and do not represent or imply
concurrence or endorsement by NCI. PMH: we thank the study participants
and staff of the Hormones and Colon Cancer study. WHI: we thank the WHI
investigators and staff for their dedication, and the study participants
for making the program possible. A full listing of WHI investigators can
be found at
https://cleo.whi.org/researchers/Documents%20%20Write%20a%20Paper/WHI%20
Investigator%20Short%20List.pdf. ACC: we thank all study participants
and research staff of all studies for their contributions and commitment
to this project, Regina Courtney for DNA preparation and Jing He for
data processing.
NR 54
TC 14
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U1 4
U2 13
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD JUL
PY 2015
VL 6
AR 7138
DI 10.1038/ncomms8138
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CO0NZ
UT WOS:000358850000001
PM 26151821
ER
PT J
AU Zhang, FL
Patel, DM
Colavita, K
Rodionova, I
Buckley, B
Scott, DA
Kumar, A
Shabalina, SA
Saha, S
Chernov, M
Osterman, AL
Kashina, A
AF Zhang, Fangliang
Patel, Devang M.
Colavita, Kristen
Rodionova, Irina
Buckley, Brian
Scott, David A.
Kumar, Akhilesh
Shabalina, Svetlana A.
Saha, Sougata
Chernov, Mikhail
Osterman, Andrei L.
Kashina, Anna
TI Arginylation regulates purine nucleotide biosynthesis by enhancing the
activity of phosphoribosyl pyrophosphate synthase
SO NATURE COMMUNICATIONS
LA English
DT Article
ID SACCHAROMYCES-CEREVISIAE; SYNTHETASE; EXPRESSION; PROTEIN; CLONING;
SERINE; CANCER; ENZYME; GENES; PRPS2
AB Protein arginylation is an emerging post-translational modification that targets a number of metabolic enzymes; however, the mechanisms and downstream effects of this modification are unknown. Here we show that lack of arginylation renders cells vulnerable to purine nucleotide synthesis inhibitors and affects the related glycine and serine biosynthesis pathways. We show that the purine nucleotide biosynthesis enzyme PRPS2 is selectively arginylated, unlike its close homologue PRPS1, and that arginylation of PRPS2 directly facilitates its biological activity. Moreover, selective arginylation of PRPS2 but not PRPS1 is regulated through a coding sequence-dependent mechanism that combines elements of mRNA secondary structure with lysine residues encoded near the N-terminus of PRPS1. This mechanism promotes arginylation-specific degradation of PRPS1 and selective retention of arginylated PRPS2 in vivo. We therefore demonstrate that arginylation affects both the activity and stability of a major metabolic enzyme.
C1 [Zhang, Fangliang; Colavita, Kristen; Saha, Sougata; Kashina, Anna] Univ Penn, Sch Vet Med, Philadelphia, PA 19104 USA.
[Zhang, Fangliang; Patel, Devang M.; Kumar, Akhilesh] Univ Miami, Sch Med, Miami, FL 33136 USA.
[Zhang, Fangliang; Patel, Devang M.; Kumar, Akhilesh] Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA.
[Rodionova, Irina; Scott, David A.; Osterman, Andrei L.] Sanford Burnham Med Res Inst, La Jolla, CA 92037 USA.
[Buckley, Brian; Chernov, Mikhail] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
[Shabalina, Svetlana A.] NIH, Natl Ctr Biotechnol Informat, NLM, Bethesda, MD 20894 USA.
[Saha, Sougata] Tezpur Univ, Dept Mol Biol & Biotechnol, Napaam 784028, India.
RP Kashina, A (reprint author), Univ Penn, Sch Vet Med, Philadelphia, PA 19104 USA.
EM akashina@vet.upenn.edu
OI Patel, Devang/0000-0002-0375-2318
FU NIH [GM104003, GM117984, GM107333]; Pilot Grant from the Mari Lowe
Center for Comparative Oncology; ACS [IRG 98-277-13]; Sylvester
Comprehensive Cancer Center Developmental Grant; Intramural Research
Programs of the National Library of Medicine
FX This work was supported by NIH grants GM104003 and GM117984 and the
Pilot Grant from the Mari Lowe Center for Comparative Oncology to A.Ka.,
ACS IRG 98-277-13, NIH grant GM107333, and Sylvester Comprehensive
Cancer Center Developmental Grant to F. Z., and the Intramural Research
Programs of the National Library of Medicine to S.A.S.
NR 25
TC 5
Z9 6
U1 2
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD JUL
PY 2015
VL 6
AR 7517
DI 10.1038/ncomms8517
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CO0OM
UT WOS:000358851500001
PM 26175007
ER
PT J
AU Grady, PA
AF Grady, Patricia A.
TI National Institute of Nursing Research commentary on the Idea Festival
for Nursing Science Education
SO NURSING OUTLOOK
LA English
DT Article
ID FUTURE
C1 NINR, NIH, Bethesda, MD 20817 USA.
RP Grady, PA (reprint author), NINR, NIH, 6701 Democracy Blvd,Suite 710, Bethesda, MD 20817 USA.
EM info@ninr.nih.gov
NR 24
TC 3
Z9 3
U1 3
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0029-6554
EI 1528-3968
J9 NURS OUTLOOK
JI Nurs. Outlook
PD JUL-AUG
PY 2015
VL 63
IS 4
BP 432
EP 435
DI 10.1016/j.outlook.2015.02.006
PG 4
WC Nursing
SC Nursing
GA CN6NT
UT WOS:000358552200010
PM 26026890
ER
PT J
AU Jones, CT
Hastings, C
Wilson, LL
AF Jones, Carolynn Thomas
Hastings, Clare
Wilson, Lynda Law
TI Research nurse manager perceptions about research activities performed
by non-nurse clinical research coordinators
SO NURSING OUTLOOK
LA English
DT Article
DE Clinical research; Research nurse manager; Nominal group process;
Clinical research coordinator; Licensure; Clinical research nurse
AB Objectives: There has been limited research to document differences in roles between nurses and non-nurses who assume clinical research coordination and management roles. Several authors have suggested that there is no acknowledged guidance for the licensure requirements for research study coordinators and that some non-nurse research coordinators may be assuming roles that are outside of their (legal scopes of practice. There is a need for further research on issues related to the delegation of clinical research activities to non-nurses.
Methods: This study used nominal group process focus groups to identify perceptions of experienced research nurse managers at an academic health science center in the Southern United States about the clinical research activities that are being performed by non-nurse clinical research coordinators without supervision that they believed should only be performed by a nurse or under the supervision of a nurse.
Results: A total of 13 research nurse managers volunteered to be contacted about the study. Of those, 8 participated in two separate nominal group process focus group sessions. The group members initially identified 22 activities that they felt should only be performed by a nurse or under the direct supervision of a nurse.
Conclusions: After discussion and clarification of results, activities were combined into 12 categories of clinical research activities that participants believed should only be performed by a nurse or under the direct supervision of a nurse.
C1 [Jones, Carolynn Thomas; Wilson, Lynda Law] Univ Alabama Birmingham, Sch Nursing, Birmingham, AL USA.
[Hastings, Clare] NIH, Ctr Clin, Bethesda, MD 20892 USA.
RP Jones, CT (reprint author), Ohio State Univ, Coll Nursing, 4317 Corinth Dr, Birmingham, AL 35213 USA.
EM jones.5342@osu.edu
RI Jones, Carolynn/F-1525-2015;
OI Jones, Carolynn/0000-0002-0669-7860
NR 33
TC 0
Z9 0
U1 3
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0029-6554
EI 1528-3968
J9 NURS OUTLOOK
JI Nurs. Outlook
PD JUL-AUG
PY 2015
VL 63
IS 4
BP 474
EP 483
DI 10.1016/j.outlook.2015.02.002
PG 10
WC Nursing
SC Nursing
GA CN6NT
UT WOS:000358552200016
PM 26081563
ER
PT J
AU Cashion, AK
Grady, PA
AF Cashion, Ann K.
Grady, Patricia A.
TI The National Institutes of Health/National Institutes of Nursing
Research intramural research program and the development of the National
Institutes of Health Symptom Science Model
SO NURSING OUTLOOK
LA English
DT Article
DE Biomarkers; Genotype; Model; Phenotype; Research; Symptom science
AB The National Institute of Nursing Research (NINR) intramural research program conducts basic and biobehavioral symptom science research and provides training opportunities to the next generation of scientists. Recently, the NINR developed the Symptom Science Model to guide research. The model begins by identifying a complex symptom, which is then characterized into a phenotype with biological and clinical data, followed by the application of genomic and other discovery methodologies to illuminate targets for therapeutic and clinical interventions. Using the Symptom Science Model, the intramural program organizes and implements biobehavioral, symptom management, and tissue injury research. The model is also used as a framework for training and career development opportunities including on-campus trainings and research fellowship. The scientific goal of the intramural program is to enhance patient outcomes including health-related quality of life. Achieving this goal requires a long-term vision, continued resource investments, and a commitment to mentoring our next generation of scientists.
C1 [Cashion, Ann K.] NINR, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Grady, Patricia A.] NINR, NIH, Bethesda, MD 20892 USA.
RP Cashion, AK (reprint author), 3 Ctr Dr,RM 5E26, Bethesda, MD 20892 USA.
EM Ann.cashion@nih.gov
FU National Institute of Nursing Research (NINR), National Institutes of
Health (NIH) [ZIANR000030]
FX This project was supported by funding from the National Institute of
Nursing Research (NINR), National Institutes of Health (NIH, Grant
number ZIANR000030). The authors wish to thank NINR Division of
Intramural Research scientists, Drs. Leorey Saligan, Wendy Henderson,
and Jessica Gill, for their insight into the development of the NIH
Symptom Science Model and as well as Dr. Rebecca Hawes, for editorial
assistance.
NR 1
TC 9
Z9 9
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0029-6554
EI 1528-3968
J9 NURS OUTLOOK
JI Nurs. Outlook
PD JUL-AUG
PY 2015
VL 63
IS 4
BP 484
EP 487
DI 10.1016/j.outlook.2015.03.001
PG 4
WC Nursing
SC Nursing
GA CN6NT
UT WOS:000358552200017
PM 26187087
ER
PT J
AU Selmansberger, M
Feuchtinger, A
Zurnadzhy, L
Michna, A
Kaiser, JC
Abend, M
Brenner, A
Bogdanova, T
Walch, A
Unger, K
Zitzelsberger, H
Hess, J
AF Selmansberger, M.
Feuchtinger, A.
Zurnadzhy, L.
Michna, A.
Kaiser, J. C.
Abend, M.
Brenner, A.
Bogdanova, T.
Walch, A.
Unger, K.
Zitzelsberger, H.
Hess, J.
TI CLIP2 as radiation biomarker in papillary thyroid carcinoma
SO ONCOGENE
LA English
DT Article
ID INDUCED GENOMIC INSTABILITY; LOW-DOSE IRRADIATION; GENE-EXPRESSION DATA;
CHERNOBYL ACCIDENT; IONIZING-RADIATION; CANCER; PROTEIN; REARRANGEMENTS;
TRANSPORT; CHILDREN
AB A substantial increase in papillary thyroid carcinoma (PTC) among children exposed to the radioiodine fallout has been one of the main consequences of the Chernobyl reactor accident. Recently, the investigation of PTCs from a cohort of young patients exposed to the post-Chernobyl radioiodine fallout at very young age and a matched nonexposed control group revealed a radiation-specific DNA copy number gain on chromosomal band 7q11.23 and the radiation-associated mRNA overexpression of CLIP2. In this study, we investigated the potential role of CLIP2 as a radiation marker to be used for the individual classification of PTCs into CLIP2-positive and - negative cases-a prerequisite for the integration of CLIP2 into epidemiological modelling of the risk of radiation-induced PTC. We were able to validate the radiation-associated CLIP2 overexpression at the protein level by immunohistochemistry (IHC) followed by relative quantification using digital image analysis software (P = 0.0149). Furthermore, we developed a standardized workflow for the determination of CLIP2-positive and - negative cases that combines visual CLIP2 IHC scoring and CLIP2 genomic copy number status. In addition to the discovery cohort (n = 33), two independent validation cohorts of PTCs (n = 115) were investigated. High sensitivity and specificity rates for all three investigated cohorts were obtained, demonstrating robustness of the developed workflow. To analyse the function of CLIP2 in radiation-associated PTC, the CLIP2 gene regulatory network was reconstructed using global mRNA expression data from PTC patient samples. The genes comprising the first neighbourhood of CLIP2 (BAG2, CHST3, KIF3C, NEURL1, PPIL3 and RGS4) suggest the involvement of CLIP2 in the fundamental carcinogenic processes including apoptosis, mitogen-activated protein kinase signalling and genomic instability. In our study, we successfully developed and independently validated a workflow for the typing of PTC clinical samples into CLIP2-positive and CLIP2-negative and provided first insights into the CLIP2 interactome in the context of radiation-associated PTC.
C1 [Selmansberger, M.; Michna, A.; Unger, K.; Zitzelsberger, H.; Hess, J.] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Radiat Cytogenet, D-85764 Neuherberg, Germany.
[Feuchtinger, A.; Walch, A.] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Analyt Pathol, D-85764 Neuherberg, Germany.
[Zurnadzhy, L.; Bogdanova, T.] Natl Acad Med Sci Ukraine, Inst Endocrinol & Metab, Kiev, Ukraine.
[Kaiser, J. C.] German Res Ctr Environm Hlth GmbH, Helmholtz Zentrum Munchen, Inst Radiat Protect, Neuherberg, Germany.
[Abend, M.] Bundeswehr Inst Radiobiol, Munich, Germany.
[Brenner, A.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Unger, K.; Zitzelsberger, H.; Hess, J.] German Res Ctr Environm Hlth GmbH, Helmholtz Zentrum Munchen, Clin Cooperat Grp Personalized Radiotherapy Head, D-85764 Neuherberg, Germany.
RP Hess, J (reprint author), German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Radiat Cytogenet, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany.
EM julia.hess@helmholtz-muenchen.de
RI Walch, Axel/B-4554-2012;
OI Walch, Axel/0000-0001-5578-4023; HeSS, Julia/0000-0001-9860-1426; Unger,
Kristian/0000-0002-0374-2320
FU European Commission, EpiRadBio project, FP7 [269553]; European
Commission, DoReMi project [249689]
FX We thank the International Pathology Panel of the Chernobyl Tissue Bank
for confirmation of diagnosis: Professors A Abrosimov, TI Bogdanova, G
Fadda, G Hant, V LiVolsi, J Rosai and ED Williams; The Chernobyl Tissue
Bank for collection of thyroid tissue samples; Professor G Thomas for
establishing the matched Genrisk-T cohort; Dr Peter Jacob for discussion
and determination of the proportion of radiation-induced tumours among
the exposed cases in the UkrAm cohort; U Buchholz, C Innerlohinger, E
Konhauser, CM Pfluger and A Selmaier for technical support; and H
Braselmann for mathematical/statistical support. This study was
supported by the European Commission, EpiRadBio project, FP7 Grant No.
269553 and in part by the European Commission, DoReMi project, Grant No.
249689.
NR 66
TC 6
Z9 7
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
EI 1476-5594
J9 ONCOGENE
JI Oncogene
PD JUL
PY 2015
VL 34
IS 30
BP 3917
EP 3925
DI 10.1038/onc.2014.311
PG 9
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA CN6KR
UT WOS:000358544200004
PM 25284583
ER
PT J
AU Bai, XL
Zhang, Q
Ye, LY
Liang, F
Sun, X
Chen, Y
Hu, QD
Fu, QH
Su, W
Chen, Z
Zhuang, ZP
Liang, TB
AF Bai, X. L.
Zhang, Q.
Ye, L. Y.
Liang, F.
Sun, X.
Chen, Y.
Hu, Q. D.
Fu, Q. H.
Su, W.
Chen, Z.
Zhuang, Z. P.
Liang, T. B.
TI Myocyte enhancer factor 2C regulation of hepatocellular carcinoma via
vascular endothelial growth factor and Wnt/beta-catenin signaling
SO ONCOGENE
LA English
DT Article
ID BREAST-CANCER CELLS; MESENCHYMAL TRANSITION; VASCULOGENIC MIMICRY;
BETA-CATENIN; TUMOR-CELL; TRANSCRIPTION; MEF2C; EXPRESSION; PROGRESSION;
MUTATIONS
AB Hepatocellular carcinoma (HCC) is one of the leading malignancies worldwide. Myocyte enhancer factor 2C (MEF2C) was traditionally regarded as a development-associated factor and was recently reported to be an oncogene candidate. We have previously reported overexpression of MEF2C in HCC; however, the roles of MEF2C in HCC remain to be clarified. In this study, HCC cell lines and a xenograft mouse model were used to determine the functions of MEF2C in vitro and in vivo, respectively. Specific plasmids and small interfering RNA were used to upregulate and downregulate MEF2C expression, respectively. Functional assays were performed to assess the influence of MEF2C on cell proliferation, and VEGF-induced vasculogenic mimicry, migration/invasion as well as angiogenesis. Co-immunoprecipitation was conducted to identify the interaction of MEF2C and beta-catenin. Human HCC tissue microarrays were used to investigate correlations among MEF2C, beta-catenin and involved biomarkers. MEF2C was found to mediate VEGF-induced vasculogenic mimicry, angiogenesis and migration/invasion, with involvement of the p38 MAPK and PKC signaling pathways. However, MEF2C itself inhibited tumor growth in vitro and in vivo. MEF2C was upregulated by and directly interacted with beta-catenin. The nuclear translocation of beta-catenin blocked by MEF2C was responsible for MEF2C-mediated growth inhibition. The nuclear translocation of MEF2C was associated with intracellular calcium signaling induced by beta-catenin. HCC microarrays showed correlations of nuclear MEF2C with the angiogenesis-associated biomarker, CD31, and cytosolic MEF2C with the proliferation-associated biomarker, Ki-67. MEF2C showed double-edged activities in HCC, namely mediating VEGF-induced malignancy enhancement while inhibiting cancer proliferation via blockade of Wnt/beta-catenin signaling. The overall effect of MEF2C in HCC progression regulation was dictated by its subcellular distribution. This should be determined prior to any MEF2C-associated intervention in HCC.
C1 [Bai, X. L.; Zhang, Q.; Ye, L. Y.; Sun, X.; Hu, Q. D.; Fu, Q. H.; Su, W.; Liang, T. B.] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Hepatobiliary & Pancreat Surg, Hangzhou 310009, Zhejiang, Peoples R China.
[Bai, X. L.; Zhang, Q.; Ye, L. Y.; Liang, T. B.] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Key Lab Canc Prevent & Intervent, Hangzhou 310009, Zhejiang, Peoples R China.
[Liang, F.] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Neurosurg, Hangzhou 310009, Zhejiang, Peoples R China.
[Chen, Y.] Zhejiang Univ, Sch Med, Childrens Hosp, Dept Gen Surg, Hangzhou 310009, Zhejiang, Peoples R China.
[Chen, Z.] Zhejiang Chinese Med Univ, Zhejiang Hosp Tradit Chinese Med, Zhejiang Key Lab Gastrointestinal Pathophysiol, Hangzhou, Zhejiang, Peoples R China.
[Zhuang, Z. P.] NINDS, NIH, Bethesda, MD 20892 USA.
RP Liang, TB (reprint author), Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Hepatobiliary & Pancreat Surg, 88 Jiefang Rd, Hangzhou 310009, Zhejiang, Peoples R China.
EM liangtingbo@zju.edu.cn
RI Hu, Qida/B-4558-2009
OI Hu, Qida/0000-0002-9092-7808
FU National Natural Science Foundation of China [81171884]; National Key
Basic Research Program of China [2014CB542101]; Ministry-Province
Co-supportive Project of China; Innovation and High-Level Talent
Training Program of Department of Health of Zhejiang
FX We thank Professor Xu Qiang (State Key Laboratory of Pharmaceutical
Biotechnology, School of Life Sciences, Nanjing University, China) for
the generous gift of MEF2C overexpression plasmid. We appreciate Mr Xie
Shangzhi, Mr Hu Liqiang, and Miss Chen Conglin (The Second Affiliated
Hospital, Zhejiang University School of Medicine, China) for their great
help in certain experiments. This study was financially supported by the
National Natural Science Foundation of China (No. 81171884), the
National Key Basic Research Program of China (No. 2014CB542101), the
Ministry-Province Co-supportive Project of China, and Innovation and
High-Level Talent Training Program of Department of Health of Zhejiang.
NR 38
TC 16
Z9 16
U1 5
U2 17
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
EI 1476-5594
J9 ONCOGENE
JI Oncogene
PD JUL
PY 2015
VL 34
IS 31
BP 4089
EP 4097
DI 10.1038/onc.2014.337
PG 9
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA CN9PE
UT WOS:000358780500007
PM 25328135
ER
PT J
AU Mansoor, A
Bagci, U
Foster, B
Xu, ZY
Papadakis, GZ
Folio, LR
Udupa, JK
Mollura, DJ
AF Mansoor, Awais
Bagci, Ulas
Foster, Brent
Xu, Ziyue
Papadakis, Georgios Z.
Folio, Les R.
Udupa, Jayaram K.
Mollura, Daniel J.
TI Segmentation and Image Analysis of Abnormal Lungs at CT: Current
Approaches, Challenges, and Future Trends
SO RADIOGRAPHICS
LA English
DT Article
ID COMPUTER-AIDED DIAGNOSIS; AUTOMATED NODULE DETECTION; CHEST CT;
PULMONARY INFECTIONS; OBJECT RECOGNITION; PATHOLOGICAL LUNG; TOMOGRAPHY
SCANS; CLASSIFICATION; ALGORITHM; QUANTIFICATION
AB The computer-based process of identifying the boundaries of lung from surrounding thoracic tissue on computed tomographic (CT) images, which is called segmentation, is a vital first step in radiologic pulmonary image analysis. Many algorithms and software platforms provide image segmentation routines for quantification of lung abnormalities; however, nearly all of the current image segmentation approaches apply well only if the lungs exhibit minimal or no pathologic conditions. When moderate to high amounts of disease or abnormalities with a challenging shape or appearance exist in the lungs, computer-aided detection systems may be highly likely to fail to depict those abnormal regions because of inaccurate segmentation methods. In particular, abnormalities such as pleural effusions, consolidations, and masses often cause inaccurate lung segmentation, which greatly limits the use of image processing methods in clinical and research contexts. In this review, a critical summary of the current methods for lung segmentation on CT images is provided, with special emphasis on the accuracy and performance of the methods in cases with abnormalities and cases with exemplary pathologic findings. The currently available segmentation methods can be divided into five major classes: (a) thresholding-based, (b) region-based, (c) shapebased, (d) neighboring anatomy-guided, and (e) machine learning-based methods. The feasibility of each class and its shortcomings are explained and illustrated with the most common lung abnormalities observed on CT images. In an overview, practical applications and evolving technologies combining the presented approaches for the practicing radiologist are detailed. (C) RSNA, 2015
C1 [Mansoor, Awais; Bagci, Ulas; Foster, Brent; Xu, Ziyue; Papadakis, Georgios Z.; Folio, Les R.; Udupa, Jayaram K.; Mollura, Daniel J.] NIH, Ctr Infect Dis Imaging, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA.
RP Bagci, U (reprint author), Univ Cent Florida, Ctr Comp Vis Res, HEC 221,4328 Scorpius St, Orlando, FL 32816 USA.
EM Bagci@crcv.ucf.edu
OI Bagci, Ulas/0000-0001-7379-6829
FU Intramural Programs of the Center for Infectious Disease Imaging;
National Institute of Allergy and Infectious Diseases; National
Institute of Biomedical Imaging and Bioengineering, at the National
Institutes of Health
FX The research was supported by the Intramural Programs of the Center for
Infectious Disease Imaging, the National Institute of Allergy and
Infectious Diseases, and the National Institute of Biomedical Imaging
and Bioengineering, at the National Institutes of Health. All authors
are or were employees of the National Institutes of Health.
NR 68
TC 5
Z9 5
U1 6
U2 19
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0271-5333
J9 RADIOGRAPHICS
JI Radiographics
PD JUL-AUG
PY 2015
VL 35
IS 4
BP 1056
EP 1076
DI 10.1148/rg.2015140232
PG 21
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA CN5DQ
UT WOS:000358450400007
PM 26172351
ER
PT J
AU Hainer, C
Mosienko, V
Koutsikou, S
Crook, JJ
Gloss, B
Kasparov, S
Lumb, BM
Alenina, N
AF Hainer, Cornelia
Mosienko, Valentina
Koutsikou, Stella
Crook, Jonathan J.
Gloss, Bernd
Kasparov, Sergey
Lumb, Bridget M.
Alenina, Natalia
TI Beyond Gene Inactivation: Evolution of Tools for Analysis of
Serotonergic Circuitry
SO ACS CHEMICAL NEUROSCIENCE
LA English
DT Review
DE Serotonergic system; Cre recombinase; optogenetics; Pet1; SERT; TPH2
ID BODY-TEMPERATURE CONTROL; TRYPTOPHAN-HYDROXYLASE ISOFORM; DORSAL RAPHE
NUCLEUS; NORMAL ANXIETY-LIKE; CRE RECOMBINASE; NEURON INHIBITION;
BRAIN-SEROTONIN; TRANSGENIC MICE; MOLECULAR-GENETICS; DEVELOPMENTAL ROLE
AB In the brain, serotonin (5-hydroxytryptamine, 5-HT) controls a multitude of physiological and behavioral functions. Serotonergic neurons in the raphe nuclei give rise to a complex and extensive network of axonal projections throughout the whole brain. A major challenge in the analysis of these circuits is to understand how the serotonergic networks are linked to the numerous functions of this neurotransmitter. In the past, many studies employed approaches to inactivate different genes involved in serotonergic neuron formation, 5-HT transmission, or 5-HT metabolism. Although these approaches have contributed significantly to our understanding of serotonergic circuits, they usually result in life-long gene inactivation. As a consequence, compensatory changes in serotonergic and other neurotransmitter systems may occur and complicate the interpretation of the observed phenotypes. To dissect the complexity of the serotonergic system with greater precision, approaches to reversibly manipulate subpopulations of serotonergic neurons are required. In this review, we summarize findings on genetic animal models that enable control of 5-HT neuronal activity or mapping of the serotonergic system. This includes a comparative analysis of several mouse and rat lines expressing Cre or Flp recombinases under Tph2, Sert, or Pet1 promoters with a focus on specificity and recombination efficiency. We further introduce applications for Cre-mediated cell-type specific gene expression to optimize spatial and temporal precision for the manipulation of serotonergic neurons. Finally, we discuss other temporally regulated systems, such as optogenetics and designer receptors exclusively activated by designer drugs (DREADD) approaches to control 5-HT neuron activity.
C1 [Hainer, Cornelia; Alenina, Natalia] Max Delbruck Ctr Mol Med MDC, D-13125 Berlin, Germany.
[Mosienko, Valentina; Koutsikou, Stella; Crook, Jonathan J.; Kasparov, Sergey; Lumb, Bridget M.] Univ Bristol, Bristol BS8 1TD, Avon, England.
[Gloss, Bernd] NIEHS, Durham, NC 27709 USA.
[Alenina, Natalia] St Petersburg State Univ, Inst Translat Biomed, St Petersburg 199034, Russia.
RP Mosienko, V (reprint author), Univ Bristol, Bristol BS8 1TD, Avon, England.
EM valentina.mosienko@bristol.ac.uk
OI Mosienko, Valentina/0000-0002-8562-532X
FU European Molecular Biology Organization (EMBO) [ASTF 72-2014]; Russian
Science Foundation [14-50-00069]; Federation of European Neuroscience
(FENS) (NENS)
FX This work was supported by fellowship from the European Molecular
Biology Organization (EMBO, Grant ASTF 72-2014) and in part by the Grant
from the Russian Science Foundation, No. 14-50-00069 to NA, and from the
Federation of European Neuroscience (FENS) to V.M. (NENS, 2013).
NR 140
TC 2
Z9 2
U1 2
U2 16
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1948-7193
J9 ACS CHEM NEUROSCI
JI ACS Chem. Neurosci.
PD JUL
PY 2015
VL 6
IS 7
SI SI
BP 1116
EP 1129
DI 10.1021/acschemneuro.5b00045
PG 14
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences
& Neurology
GA CN1OI
UT WOS:000358188900017
PM 26132472
ER
PT J
AU Anastasio, NC
Stutz, SJ
Fink, LHL
Swinford-Jackson, SE
Sears, RM
DiLeone, RJ
Rice, KC
Moeller, FG
Cunningham, KA
AF Anastasio, Noelle C.
Stutz, Sonja J.
Fink, Latham H. L.
Swinford-Jackson, Sarah E.
Sears, Robert M.
DiLeone, Ralph J.
Rice, Kenner C.
Moeller, F. Gerard
Cunningham, Kathryn A.
TI Serotonin (5-HT) 5-HT2A Receptor (5-HT2AR):5-HT2cR Imbalance in Medial
Prefrontal Cortex Associates with Motor Impulsivity
SO ACS CHEMICAL NEUROSCIENCE
LA English
DT Article
DE 1-Choice serial reaction time task; 5-HT2A receptor; 5-HT2c receptor;
motor impulsivity; medial prefrontal cortex; serotonin
ID REACTION-TIME-TASK; CALLOSAL PROJECTION NEURONS; NUCLEUS-ACCUMBENS;
MESSENGER-RNA; PARA-CHLOROPHENYLALANINE; RESPONSE-INHIBITION;
SELF-STIMULATION; RAT HIPPOCAMPUS; BRAIN-REGIONS; BEHAVIOR
AB A feature of multiple neuropsychiatric disorders is motor impulsivity. Recent studies have implicated serotonin (5-HT) systems in medial prefrontal cortex (mPFC) in mediating individual differences in motor impulsivity, notably the 5-HT2AR receptor (5-HT2AR) and 5-HT2cR. We investigated the hypothesis that differences in the ratio of 5HT(2A)R:5-HT2cR protein expression in mPFC would predict the individual level of motor impulsivity and that the engineered loss of the 5-HT2cR would result in high motor impulsivity concomitant with elevated 5-HT2AR expression and pharmacological sensitivity to the selective 5-HT2AR antagonist M100907. High and low impulsive rats were identified in a 1-choice serial reaction time task. Native protein levels of the 5-HT2AR and the 5-HT2cR predicted the intensity of motor impulsivity and the 5-HT2AR:5-HT2cR ratio in mPFC positively correlated with levels of premature responses in individual outbred rats. The possibility that the 5-HT2AR and 5-HT2cR act in concert to control motor impulsivity is supported by the observation that high phenotypic motor impulsivity associated with a diminished mPFC synaptosomal 5-HT2AR:5-HT2cR protein:protein interaction. Knockdown of mPFC 5-HT2cR resulted in increased motor impulsivity and triggered a functional disruption of the local S-HT2AR:5-HT2cR balance as evidenced by a compensatory upregulation of 5-HT2AR protein expression and a leftward shift in the potency of MI00907 to suppress impulsive behavior. We infer that there is an interactive relationship between the mPFC 5-HT2AR and 5-HT2cR, and that a 5-HT2AR:5HT(2c)R imbalance may be a functionally relevant mechanism underlying motor impulsivity.
C1 [Anastasio, Noelle C.; Stutz, Sonja J.; Fink, Latham H. L.; Swinford-Jackson, Sarah E.; Cunningham, Kathryn A.] Univ Texas Med Branch, Ctr Addict Res, Galveston, TX 77555 USA.
[Anastasio, Noelle C.; Cunningham, Kathryn A.] Univ Texas Med Branch, Dept Pharmacol & Toxicol, Galveston, TX 77555 USA.
[Sears, Robert M.; DiLeone, Ralph J.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA.
[Rice, Kenner C.] NIDA, Chem Biol Res Branch, DHHS, NIH, Bethesda, MD 20892 USA.
[Moeller, F. Gerard] Virginia Commonwealth Univ, Sch Med, Dept Psychiat, Richmond, VA 23298 USA.
RP Cunningham, KA (reprint author), Univ Texas Med Branch, Ctr Addict Res, Galveston, TX 77555 USA.
EM kcunning@utmb.edu
FU NIDA [K99 DA033374, F30 DA034488, F31 DA035620, T32 DA07287, P20
DA024157, P50 DA033935, K05 DA020087]; Center for Addiction Research at
the University of Texas Medical Branch; NIH Intramural Research Programs
in the Drug Design and Synthesis Section of the Chemical Biology
Research Branch within the National Institutes of Health Intramural
Research Program of the National Institute on Drug Abuse (NIDA); NIH
Intramural Research Programs in the Drug Design and Synthesis Section of
the Chemical Biology Research Branch within the National Institutes of
Health Intramural Research Program of National Institute of Alcohol
Abuse and Alcoholism (NIAAA)
FX This work was supported by NIDA Grants K99 DA033374 (N.C.A), F30
DA034488 (L.H.L.F.), F31 DA035620 (S.E.S.-J) T32 DA07287 (L.H.L.F. and
S.E.S-J.), P20 DA024157 (K.A.C.), P50 DA033935 (K.A.C.), K05 DA020087
(K.A.C.), and the Center for Addiction Research at the University of
Texas Medical Branch. The research was also supported by the NIH
Intramural Research Programs in the Drug Design and Synthesis Section of
the Chemical Biology Research Branch within the National Institutes of
Health Intramural Research Programs of the National Institute on Drug
Abuse (NIDA) and the National Institute of Alcohol Abuse and Alcoholism
(NIAAA) (K.C.R.).
NR 95
TC 3
Z9 3
U1 1
U2 10
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1948-7193
J9 ACS CHEM NEUROSCI
JI ACS Chem. Neurosci.
PD JUL
PY 2015
VL 6
IS 7
SI SI
BP 1248
EP 1258
DI 10.1021/acschemneuro.5b00094
PG 11
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences
& Neurology
GA CN1OI
UT WOS:000358188900031
PM 26120876
ER
PT J
AU Freedman, LS
Carroll, RJ
Neuhouser, ML
Prentice, RL
Spiegelman, D
Subar, AF
Tinker, LF
Willett, W
AF Freedman, Laurence S.
Carroll, Raymond J.
Neuhouser, Marian L.
Prentice, Ross L.
Spiegelman, Donna
Subar, Amy F.
Tinker, Lesley F.
Willett, Walter
TI Institute of Medicine and National Research Council. Examining a
Developmental Approach to Childhood Obesity: The Fetal and Early
Childhood Years: Workshop in Brief. Washington, DC: The National
Academies Press, 2015 Reply
SO ADVANCES IN NUTRITION
LA English
DT Letter
C1 [Freedman, Laurence S.] Informat Management Syst Inc, Rockville, MD 20852 USA.
[Freedman, Laurence S.] Gertner Inst Epidemiol & Hlth Policy Res, Biostat Unit, Tel Hashomer, Israel.
[Carroll, Raymond J.] Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA.
[Neuhouser, Marian L.; Prentice, Ross L.; Tinker, Lesley F.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Spiegelman, Donna; Willett, Walter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Spiegelman, Donna; Willett, Walter] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Subar, Amy F.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Freedman, LS (reprint author), Informat Management Syst Inc, Rockville, MD 20852 USA.
EM lsf@actcom.co.il
FU NCI NIH HHS [R01 CA119171]
NR 5
TC 1
Z9 1
U1 0
U2 0
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 2161-8313
EI 2156-5376
J9 ADV NUTR
JI Adv. Nutr.
PD JUL
PY 2015
VL 6
IS 4
BP 489
EP 489
DI 10.3945/an.115.009118
PG 1
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA CN2AZ
UT WOS:000358224000012
PM 26178033
ER
PT J
AU Justman, J
Befus, M
Hughes, J
Wang, J
Golin, CE
Adimora, AA
Kuo, I
Haley, DF
del Rio, C
El-Sadr, WM
Rompalo, A
Mannheimer, S
Soto-Torres, L
Hodder, S
AF Justman, J.
Befus, M.
Hughes, J.
Wang, J.
Golin, C. E.
Adimora, A. A.
Kuo, I.
Haley, D. F.
del Rio, C.
El-Sadr, W. M.
Rompalo, A.
Mannheimer, S.
Soto-Torres, L.
Hodder, S.
TI Sexual Behaviors of US Women at Risk of HIV Acquisition: A Longitudinal
Analysis of Findings from HPTN 064
SO AIDS AND BEHAVIOR
LA English
DT Article
DE Sexual risk behaviors; Longitudinal patterns; Women in the US; Exchange
sex; Unprotected anal intercourse; Concurrent partnerships
ID HUMAN-IMMUNODEFICIENCY-VIRUS; UNITED-STATES; TRANSMITTED INFECTIONS;
CONCURRENT PARTNERSHIPS; AFRICAN-AMERICANS; PREVENTION TRIAL; EFFICACY
TRIAL; BLACK-MEN; TRANSMISSION; PREVALENCE
AB We describe the sexual behaviors of women at elevated risk of HIV acquisition who reside in areas of high HIV prevalence and poverty in the US. Participants in HPTN 064, a prospective HIV incidence study, provided information about individual sexual behaviors and male sexual partners in the past 6 months at baseline, 6- and 12-months. Independent predictors of consistent or increased temporal patterns for three high-risk sexual behaviors were assessed separately: exchange sex, unprotected anal intercourse (UAI) and concurrent partnerships. The baseline prevalence of each behavior was > 30 % among the 2,099 participants, 88 % reported partner(s) with > 1 HIV risk characteristic and both individual and partner risk characteristics decreased over time. Less than high school education and food insecurity predicted consistent/increased engagement in exchange sex and UAI, and partner's concurrency predicted participant concurrency. Our results demonstrate how interpersonal and social factors may influence sustained high-risk behavior by individuals and suggest that further study of the economic issues related to HIV risk could inform future prevention interventions.
C1 [Justman, J.; El-Sadr, W. M.; Mannheimer, S.] Columbia Univ, Mailman Sch Publ Hlth, ICAP, New York, NY 10032 USA.
[Befus, M.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY 10032 USA.
[Hughes, J.; Wang, J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Golin, C. E.; Adimora, A. A.] Univ N Carolina, Chapel Hill, NC USA.
[Kuo, I.] George Washington Univ, Sch Publ Hlth & Hlth Serv, Washington, DC USA.
[Haley, D. F.] FHI 360, Durham, NC USA.
[Haley, D. F.] Rollins Sch Publ Hlth, Dept Behav Sci & Hlth Educ, Atlanta, GA USA.
[del Rio, C.] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.
[del Rio, C.] Emory Univ, Ctr AIDS Res, Atlanta, GA 30322 USA.
[Rompalo, A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Mannheimer, S.] Columbia Univ Coll Phys & Surg, Harlem Hosp Ctr, New York, NY 10032 USA.
[Soto-Torres, L.] NIAID, NIH, Bethesda, MD 20892 USA.
[Hodder, S.] West Virginia Clin & Translat Sci Inst, Morgantown, WV USA.
RP Justman, J (reprint author), Columbia Univ, Mailman Sch Publ Hlth, ICAP, 722 West 168th St,Room 1315, New York, NY 10032 USA.
EM jj2158@columbia.edu
RI del Rio, Carlos/B-3763-2012
OI del Rio, Carlos/0000-0002-0153-3517
FU National Institute of Allergy and Infectious Diseases; National
Institute on Drug Abuse; National Institute of Mental Health [UM1
AI068619, U01-AI068613, UM1-AI068613, F31MH105238]; Centers for
Innovative Research to Control AIDS, Mailman School of Public Health,
Columbia University [5UM1Al069466]; University of North Carolina
Clinical Trials Unit [AI069423]; University of North Carolina Clinical
Trials Research Center of the Clinical and Translational Science Award
[RR 025747]; University of North Carolina Center for AIDS Research
[AI050410]; Emory University HIV/AIDS Clinical Trials Unit
[5UO1AI069418]; Center for AIDS Research [P30 AI050409]; Clinical and
Translational Science Award [UL1 RR025008]; Terry Beirn Community
Programs for Clinical Research on AIDS Clinical Trials Unit; Johns
Hopkins Adult AIDS Clinical Trial Unit [AI069465]; Johns Hopkins
Clinical and Translational Science Award [UL1 RR 25005]; Robert W.
Woodruff pre-doctoral fellowship of the Emory University Laney Graduate
School; Columbia University Irving Institute Clinical and Translational
Science Award [TL1 TR000082-07]
FX By the National Institute of Allergy and Infectious Diseases, National
Institute on Drug Abuse, and National Institute of Mental Health
(cooperative agreement no. UM1 AI068619, U01-AI068613, and
UM1-AI068613); Centers for Innovative Research to Control AIDS, Mailman
School of Public Health, Columbia University (5UM1Al069466); University
of North Carolina Clinical Trials Unit (AI069423); University of North
Carolina Clinical Trials Research Center of the Clinical and
Translational Science Award (RR 025747); University of North Carolina
Center for AIDS Research (AI050410); Emory University HIV/AIDS Clinical
Trials Unit (5UO1AI069418), Center for AIDS Research (P30 AI050409), and
Clinical and Translational Science Award (UL1 RR025008); Terry Beirn
Community Programs for Clinical Research on AIDS Clinical Trials Unit;
Johns Hopkins Adult AIDS Clinical Trial Unit (AI069465), Johns Hopkins
Clinical and Translational Science Award (UL1 RR 25005); Robert W.
Woodruff pre-doctoral fellowship of the Emory University Laney Graduate
School; the National Institute of Mental Health (F31MH105238); and
Columbia University Irving Institute Clinical and Translational Science
Award TL1 TR000082-07.
NR 45
TC 3
Z9 3
U1 4
U2 9
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1090-7165
EI 1573-3254
J9 AIDS BEHAV
JI AIDS Behav.
PD JUL
PY 2015
VL 19
IS 7
BP 1327
EP 1337
DI 10.1007/s10461-014-0992-8
PG 11
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA CN2KA
UT WOS:000358248600017
PM 25626889
ER
PT J
AU Liu, E
Luthman, J
Cedarbaum, JM
Schmidt, ME
Cole, PE
Hendrix, J
Carrillo, MC
Jones-Davis, D
Tarver, E
Novak, G
De Santi, S
Soares, HD
Potter, WZ
Siemers, E
Schwarz, AJ
AF Liu, Enchi
Luthman, Johan
Cedarbaum, Jesse M.
Schmidt, Mark E.
Cole, Patricia E.
Hendrix, James
Carrillo, Maria C.
Jones-Davis, Dorothy
Tarver, Erika
Novak, Gerald
De Santi, Susan
Soares, Holly D.
Potter, William Z.
Siemers, Eric
Schwarz, Adam J.
TI Perspective: The Alzheimer's Disease Neuroimaging Initiative and the
role and contributions of the Private Partner Scientific Board (PPSB)
SO ALZHEIMERS & DEMENTIA
LA English
DT Review
DE Alzheimer's Disease Neuroimaging Initiative; ADNI; Private Partner
Scientific Board; PPSB; FNIH; Foundation for the National Institutes of
Health; Pharmaceutical industry
ID CEREBROSPINAL-FLUID BIOMARKERS; RECOMMENDATIONS
AB The Alzheimer's Disease Neuroimaging Initiative (ADNI) Private Partner Scientific Board (PPSB) is comprised of representatives of private, for-profit entities (including pharmaceutical, biotechnology, diagnostics, imaging companies, and imaging contract research organizations), and nonprofit organizations that provide financial and scientific support to ADNI through the Foundation for the National Institutes of Health. The PPSB serves as an independent, open, and precompetitive forum in which all private sector and not-for-profit partners in ADNI can collaborate, share information, and offer scientific and private-sector perspectives and expertise on issues relating to the ADNI project. In this article, we review and highlight the role, activities, and contributions of the PPSB within the ADNI project, and provide a perspective on remaining unmet needs and future directions. (C) 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
C1 [Liu, Enchi] Janssen Res & Dev, Neurosci Biomarkers, Discovery, San Diego, CA 92121 USA.
[Luthman, Johan] Clin Neurosci Eisai, Neurosci Clin Dev, Woodcliff Lake, NJ USA.
[Cedarbaum, Jesse M.] Clin Dev, Cambridge, MA USA.
[Schmidt, Mark E.] Janssen Pharmaceut NV, Expt Med, Beerse, Belgium.
[Cole, Patricia E.] Takeda Pharmaceut Inc, Clin & Translat Sci Imaging, Deerfield, IL USA.
[Hendrix, James; Carrillo, Maria C.] Alzheimers Assoc, Med & Sci Relat, Chicago, IL USA.
[Jones-Davis, Dorothy; Tarver, Erika] Fdn NIH, Bethesda, MD USA.
[Novak, Gerald] Janssen Res & Dev, Neurosci Clin Dev, Titusville, NJ USA.
[De Santi, Susan] Piramal Pharma Inc, Med Affairs, Boston, MA USA.
[Soares, Holly D.] Bristol Meyer Squibb, Clin Biomarkers, Hopewell, NJ USA.
[Potter, William Z.] NIMH, Off Director, Rockville, MD 20857 USA.
[Siemers, Eric] Eli Lilly & Co, Biomed Business Unit, Alzheimers Dis Platform Team, Indianapolis, IN 46285 USA.
[Schwarz, Adam J.] Eli Lilly & Co, Tailored Therapeut, Indianapolis, IN 46285 USA.
RP Liu, E (reprint author), Janssen Res & Dev, Neurosci Biomarkers, Discovery, San Diego, CA 92121 USA.
EM eliu12@its.jnj.com
RI Schmidt, Mark/I-5052-2016
OI Schmidt, Mark/0000-0003-3417-8977
NR 28
TC 3
Z9 3
U1 1
U2 4
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 JUL
PY 2015
VL 11
IS 7
BP 840
EP 849
DI 10.1016/j.jalz.2015.04.001
PG 10
WC Clinical Neurology
SC Neurosciences & Neurology
GA CN1RS
UT WOS:000358198400011
PM 26194317
ER
PT J
AU Jones-Davis, DM
Buckholtz, N
AF Jones-Davis, Dorothy M.
Buckholtz, Neil
TI The impact of the Alzheimer's Disease Neuroimaging Initiative 2: What
role do public-private partnerships have in pushing the boundaries of
clinical and basic science research on Alzheimer's disease?
SO ALZHEIMERS & DEMENTIA
LA English
DT Review
DE ADNI; Alzheimer's disease; Public private partnerships; Consortia; FNIH;
NIA; Foundation for the National Institutes of Health; National
Institute on Aging
ID ASSOCIATION WORKGROUPS; DIAGNOSTIC GUIDELINES; NATIONAL INSTITUTE;
RECOMMENDATIONS; MILD
AB In the growing landscape of biomedical public-private-partnerships, particularly for Alzheimer's disease, the question is posed as to their value. What impacts do public-private-partnerships have on clinical and basic science research in Alzheimer's disease? The authors answer the question using the Alzheimer's Disease Neuroimaging Initiative (ADNI) as a test case and example. ADNI is an exemplar of how public-private-partnerships can make an impact not only on clinical and basic science research and practice (including clinical trials), but also of how similar partnerships using ADNI as an example, can be designed to create a maximal impact within their fields. (C) 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
C1 [Jones-Davis, Dorothy M.] Fdn Natl Inst Hlth, Bethesda, MD 20892 USA.
[Buckholtz, Neil] NIA, NIH, Bethesda, MD 20892 USA.
RP Jones-Davis, DM (reprint author), Fdn Natl Inst Hlth, Bethesda, MD 20892 USA.
EM djones-davis@fnih.org
OI Jones-Davis, Dorothy/0000-0001-7209-9183
FU NIA NIH HHS [U01 AG024904]
NR 23
TC 2
Z9 2
U1 2
U2 6
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 JUL
PY 2015
VL 11
IS 7
BP 860
EP 864
DI 10.1016/j.jalz.2015.05.006
PG 5
WC Clinical Neurology
SC Neurosciences & Neurology
GA CN1RS
UT WOS:000358198400013
PM 26194319
ER
PT J
AU Eley, TC
McAdams, TA
Rijsdijk, FV
Lichtenstein, P
Narusyte, J
Reiss, D
Spotts, EL
Ganiban, JM
Neiderhiser, JM
AF Eley, Thalia C.
McAdams, Tom. A.
Rijsdijk, Fruhling V.
Lichtenstein, Paul
Narusyte, Jurgita
Reiss, David
Spotts, Erica L.
Ganiban, Jody M.
Neiderhiser, Jenae M.
TI The Intergenerational Transmission of Anxiety: A Children-of-Twins Study
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Article
ID ENVIRONMENTAL-INFLUENCES; PARENTAL DEPRESSION; SEPARATION ANXIETY;
EXTENDED CHILDREN; MIDDLE CHILDHOOD; GENETIC-ANALYSIS; YOUNG ADULTHOOD;
MENTAL-HEALTH; SOCIAL PHOBIA; DISORDERS
AB Objective: The transmission of anxiety within families is well recognized, but the underlying processes are poorly understood. Twin studies of adolescent anxiety demonstrate both genetic and environmental influence, and multiple aspects of parenting are associated with offspring anxiety. To date, the children-of-twins design has not been used to evaluate the relative contributions of genetic transmission compared with direct transmission of anxiety from parents to their offspring.
Method: Anxiety and neuroticism measures were completed by 385 monozygotic and 486 dizygotic same-sex twin families (37% male twin pair families) from the Twin and Offspring Study in Sweden. Structural equation models tested for the presence of both genetic and environmental transmission from one generation to the next.
Results: For both anxiety and neuroticism, the models provide support for significant direct environmental transmission from parents to their adolescent offspring. In contrast, there was no evidence of significant genetic transmission.
Conclusions: The association between parental and offspring anxiety largely arises because of a direct association between parents and their children independent of genetic confounds. The lack of genetic transmission may reflect there being different genetic effects on these traits in adolescence and adulthood. Direct environmental transmission is in line with developmental theories of anxiety suggesting that children and adolescents learn anxious behaviors from their parents through a number of pathways such as modeling. Future analyses should combine children-of-twins data with child twin data in order to examine whether this direct effect solely represents parental influences on the offspring or whether it also includes child/adolescent anxiety evoking parental anxiety.
C1 [Eley, Thalia C.] Kings Coll London, MRC, Social Genet & Dev Psychiat Res Ctr, London WC2R 2LS, England.
Inst Psychiat Psychol & Neurosci, London, England.
Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
Yale Univ, Sch Med, Yale Child Study Ctr, New Haven, CT USA.
NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA.
George Washington Univ, Dept Psychol, Washington, DC 20052 USA.
Penn State Univ, Dept Psychol, University Pk, PA 16802 USA.
RP Eley, TC (reprint author), Kings Coll London, MRC, Social Genet & Dev Psychiat Res Ctr, London WC2R 2LS, England.
EM thalia.eley@kcl.ac.uk; tom.mcadams@kcl.ac.uk
FU Leverhulme Trust [RPG-210]; NIMH [R01MH54610]; National Institute for
Health Research (NIHR) Biomedical Research Centre at South London and
Maudsley NHS Foundation Trust; King's College London
FX Supported by the Leverhulme Trust (RPG-210, principal investigator,
Thalia Eley, Ph.D.). The Twin and Offspring Study in Sweden was
supported by grant R01MH54610 from NIMH.; This study presents
independent research part-funded by the National Institute for Health
Research (NIHR) Biomedical Research Centre at South London and Maudsley
NHS Foundation Trust and King's College London. The views expressed are
those of the author(s) and not necessarily those of the NHS, the NIHR,
or the Department of Health.
NR 45
TC 14
Z9 14
U1 2
U2 37
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0002-953X
EI 1535-7228
J9 AM J PSYCHIAT
JI Am. J. Psychiat.
PD JUL
PY 2015
VL 172
IS 7
BP 630
EP 637
DI 10.1176/appi.ajp.2015.14070818
PG 8
WC Psychiatry
SC Psychiatry
GA CN1OR
UT WOS:000358189800009
PM 25906669
ER
PT J
AU Roberson-Nay, R
Leibenluft, E
Brotman, MA
Myers, J
Larsson, H
Lichtenstein, P
Kendler, KS
AF Roberson-Nay, Roxann
Leibenluft, Ellen
Brotman, Melissa A.
Myers, John
Larsson, Henrik
Lichtenstein, Paul
Kendler, Kenneth S.
TI Longitudinal Stability of Genetic and Environmental Influences on
Irritability: From Childhood to Young Adulthood
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Article
ID COMORBIDITY SURVEY REPLICATION; OPPOSITIONAL DEFIANT DISORDER; MIDDLE
CHILDHOOD; TWIN; AGGRESSION; PREVALENCE; ETIOLOGY; BEHAVIOR;
ADOLESCENCE; DEPRESSION
AB Objective: Little is known about genetic influences on juvenile irritability and whether, such influences are developmentally stable and/or dynamic. This study examined the temporal pattern of genetic and environmental effects on irritability using data from a prospective, four-wave longitudinal twin study.
Method: Parents and their twin children (N=2,620 children) from the Swedish Twin Study of Child and Adolescent Development reported on the children's irritability, defined using a previously identified scale from the Child Behavior Checklist.
Results: Genetic effects differed across the sexes, with males exhibiting increasing heritability from early childhood through young adulthood and females exhibiting decreasing heritability. Genetic innovation was also more prominent in males than in females, with new genetic risk factors affecting irritability in early and late adolescence for males. Shared environment was not a primary influence on irritability for males or females. Unique, nonshared environmental factors suggested strong effects early for males followed by an attenuating influence, whereas unique environmental factors were relatively stable for females.
Conclusions: Genetic effects on irritability are developmentally dynamic from middle childhood through young adulthood, with males and females displaying differing patterns. As males age, genetic influences on irritability increase while nonshared environmental influences weaken. Genetic contributions are quite strong in females early in life but decline in importance with age. In girls, nonshared environmental influences are fairly stable throughout development.
C1 [Roberson-Nay, Roxann] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23284 USA.
Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA 23284 USA.
NIMH, Sect Bipolar Spectrum Disorders, Div Intramural Res Programs, Bethesda, MD 20892 USA.
Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
RP Roberson-Nay, R (reprint author), Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23284 USA.
EM rrobersonnay@vcu.edu
RI Brotman, Melissa/H-7409-2013
FU NIMH [K01-MH080953, R01-MH101518]; Swedish Council for Working Life and
Social Research [2004-0383]; Swedish Research Council [2004-1415];
Division of Intramural Research Programs, NIMH; Shire
FX Supported by NIMH grants K01-MH080953 and R01-MH101518 (Dr.
Roberson-Nay); the Swedish Council for Working Life and Social Research
(project 2004-0383) and the Swedish Research Council (project 2004-1415)
(Dr. Lichtenstein); and the Division of Intramural Research Programs,
NIMH (Drs. Leibenluft and Brotman).; Dr. Larsson has served as a speaker
for Eli Lilly and has received a research grant from Shire. The other
authors report no financial relationships with commercial interests.
NR 35
TC 7
Z9 7
U1 2
U2 9
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0002-953X
EI 1535-7228
J9 AM J PSYCHIAT
JI Am. J. Psychiat.
PD JUL
PY 2015
VL 172
IS 7
BP 657
EP 664
DI 10.1176/appi.ajp.2015.14040509
PG 8
WC Psychiatry
SC Psychiatry
GA CN1OR
UT WOS:000358189800012
PM 25906668
ER
PT J
AU Ghareeb, M
Leggio, L
El-Kattan, A
Akhlaghi, F
AF Ghareeb, Mwlod
Leggio, Lorenzo
El-Kattan, Ayman
Akhlaghi, Fatemeh
TI Development and validation of an UPLC-MS/MS assay for quantitative
analysis of the ghrelin receptor inverse agonist PF-5190457 in human or
rat plasma and rat brain
SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY
LA English
DT Article
DE Alcoholism; Bioanalytical methods; Ghrelin; LC-MS/MS; PF-5190457;
Pharmacokinetics
ID LC-MS/MS; ALCOHOL; SYSTEM
AB PF-5190457 is a ghrelin receptor inverse agonist that is currently undergoing clinical development for the treatment of alcoholism. Our aim was to develop and validate a simple and sensitive assay for quantitative analysis of PF-5190457 in human or rat plasma and rat brain using liquid chromatography-tandem mass spectrometry. The analyte and stable isotope internal standard were extracted from 50 mu L plasma or rat brain homogenate by protein precipitation using 0.1 % formic acid in acetonitrile. Chromatography was carried out on an Acquity UPLC BEH C18 (2.1 mm x 50 mm) column with 1.7 mu m particle size and 130 pore size. The flow rate was 0.5 mL/min and total chromatographic run time was 2.2 min. The mobile phase consisted of a gradient mixture of water: acetonitrile 95:5 % (v/v) containing 0.1 % formic acid (solvent A) and 100 % acetonitrile containing 0.1 % formic acid (solvent B). Multiple reaction monitoring was carried out in positive electro-spray ionization mode using m/z 513.35 -> aEuro parts per thousand 209.30 for PF-5190457 and m/z 518.47 -> aEuro parts per thousand 214.43 for the internal standard. The recovery ranged from 102 to 118 % with coefficient of variation (CV) less than 6 % for all matrices. The calibration curves for all matrices were linear over the studied concentration range (R (2) a parts per thousand yenaEuro parts per thousand 0.998, n = 3). The lower limit of quantification was 1 ng/mL in rat or human plasma and 0.75 ng/g in rat brain. Intra- and inter-run mean percent accuracies were between 85 and 115 % and percent imprecision was a parts per thousand currency sign15 %. The assays were successfully utilized to measure the concentration of PF-5190457 in pre-clinical and clinical pharmacology studies of the compound.
C1 [Ghareeb, Mwlod; Akhlaghi, Fatemeh] Univ Rhode Isl, Clin Pharmacokinet Res Lab, Dept Biomed & Pharmaceut Sci, Coll Pharm 495A, Kingston, RI 02881 USA.
[Leggio, Lorenzo] NIAAA, Sect Clin Psychoneuroendocrinol & Neuropsychophar, Lab Clin & Translat Studies, Bethesda, MD USA.
[Leggio, Lorenzo] NIDA, Intramural Res Program, NIH, Baltimore, MD USA.
[Leggio, Lorenzo] Brown Univ, Dept Behav & Social Sci, Ctr Alcohol & Addict Studies, Providence, RI 02903 USA.
[El-Kattan, Ayman] Pfizer Inc, Cambridge, MA 02139 USA.
RP Akhlaghi, F (reprint author), Univ Rhode Isl, Clin Pharmacokinet Res Lab, Dept Biomed & Pharmaceut Sci, Coll Pharm 495A, 7 Greenhouse Rd, Kingston, RI 02881 USA.
EM fatemeh@uri.edu
RI Leggio, Lorenzo/M-2972-2016
FU National Center for Advancing Translational Sciences (NCATS), National
Institutes of Health (NIH) [1UH2TR000963]; NIH [ZIA-AA000218]; Division
of Intramural Clinical and Biological Research of the National Institute
on Alcohol Abuse and Alcoholism (NIAAA); National Institute on Drug
Abuse (NIDA)
FX The authors would like to thank Professor Deyu Li for his help in
elucidating the fragmentation pattern of PF-5190457. This work was
supported by grant number 1UH2TR000963 (PIs: Akhlaghi and Leggio) from
the National Center for Advancing Translational Sciences (NCATS),
National Institutes of Health (NIH), and by NIH intramural funding
ZIA-AA000218 (PI: Leggio) jointly supported by the Division of
Intramural Clinical and Biological Research of the National Institute on
Alcohol Abuse and Alcoholism (NIAAA) and the Intramural Research Program
of the National Institute on Drug Abuse (NIDA).
NR 17
TC 0
Z9 0
U1 0
U2 7
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1618-2642
EI 1618-2650
J9 ANAL BIOANAL CHEM
JI Anal. Bioanal. Chem.
PD JUL
PY 2015
VL 407
IS 19
BP 5603
EP 5613
DI 10.1007/s00216-015-8730-2
PG 11
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA CN0XE
UT WOS:000358136900006
PM 25943263
ER
PT J
AU Hunt, PR
Friesen, MC
Sama, S
Ryan, L
Milton, D
AF Hunt, Phillip R.
Friesen, Melissa C.
Sama, Susan
Ryan, Louise
Milton, Donald
TI Log-Linear Modeling of Agreement among Expert Exposure Assessors
SO ANNALS OF OCCUPATIONAL HYGIENE
LA English
DT Article
DE asthma; epidemiology; expert judgement; exposure assessment methodology;
sensitization
ID OCCUPATIONAL EXPOSURES; INTERRATER AGREEMENT; RETROSPECTIVE ASSESSMENT;
ORDINAL SCALE; LOW KAPPA; RATINGS; RELIABILITY; POPULATION; RATERS;
INFORMATION
AB Background: Evaluation of expert assessment of exposure depends, in the absence of a validation measurement, upon measures of agreement among the expert raters. Agreement is typically measured using Cohen's Kappa statistic, however, there are some well-known limitations to this approach. We demonstrate an alternate method that uses log-linear models designed to model agreement. These models contain parameters that distinguish between exact agreement (diagonals of agreement matrix) and non-exact associations (off-diagonals). In addition, they can incorporate covariates to examine whether agreement differs across strata.
Methods: We applied these models to evaluate agreement among expert ratings of exposure to sensitizers (none, likely, high) in a study of occupational asthma.
Results: Traditional analyses using weighted kappa suggested potential differences in agreement by blue/white collar jobs and office/non-office jobs, but not case/control status. However, the evaluation of the covariates and their interaction terms in log-linear models found no differences in agreement with these covariates and provided evidence that the differences observed using kappa were the result of marginal differences in the distribution of ratings rather than differences in agreement. Differences in agreement were predicted across the exposure scale, with the likely moderately exposed category more difficult for the experts to differentiate from the highly exposed category than from the unexposed category.
Conclusions: The log-linear models provided valuable information about patterns of agreement and the structure of the data that were not revealed in analyses using kappa. The models' lack of dependence on marginal distributions and the ease of evaluating covariates allow reliable detection of observational bias in exposure data.
C1 [Hunt, Phillip R.] Evidera, Retrospect Observat Studies, Lexington, MA 02420 USA.
[Friesen, Melissa C.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Sama, Susan] Univ Massachusetts, Dept Work Environm, Lowell, MA 01854 USA.
[Ryan, Louise] Univ Technol Sidney, Sch Math Sci, Ultimo, NSW 2007, Australia.
[Milton, Donald] Univ Maryland, Sch Publ Hlth, Maryland Inst Appl Environm Hlth, College Pk, MD 20742 USA.
RP Hunt, PR (reprint author), Evidera, Retrospect Observat Studies, 430 Bedford St,Suite 300, Lexington, MA 02420 USA.
EM phillip.hunt@evidera.com
RI Ryan, Louise/A-4562-2009; Milton, Donald/G-3286-2010; Friesen,
Melissa/A-5362-2009
OI Ryan, Louise/0000-0001-5957-2490; Milton, Donald/0000-0002-0550-7834;
FU National Heart, Lung and Blood Institute of the National Institutes of
Health [HL61302]; National Institute of Environmental Health Sciences
Occupational and Environmental Health Center [2P30 ES 00002]; Intramural
Research Program of the National Cancer Institute
FX Supported by a research grants HL61302 from the National Heart, Lung and
Blood Institute of the National Institutes of Health, and 2P30 ES 00002
from the National Institute of Environmental Health Sciences
Occupational and Environmental Health Center. MCF was supported by the
Intramural Research Program of the National Cancer Institute.
NR 38
TC 0
Z9 0
U1 1
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0003-4878
EI 1475-3162
J9 ANN OCCUP HYG
JI Ann. Occup. Hyg.
PD JUL
PY 2015
VL 59
IS 6
BP 764
EP 774
DI 10.1093/annhyg/mev011
PG 11
WC Public, Environmental & Occupational Health; Toxicology
SC Public, Environmental & Occupational Health; Toxicology
GA CN1HH
UT WOS:000358168900007
PM 25748517
ER
PT J
AU Weindel, CG
Richey, LJ
Bolland, S
Mehta, AJ
Kearney, JF
Huber, BT
AF Weindel, Chi G.
Richey, Lauren J.
Bolland, Silvia
Mehta, Abhiruchi J.
Kearney, John F.
Huber, Brigitte T.
TI B cell autophagy mediates TLR7-dependent autoimmunity and inflammation
SO AUTOPHAGY
LA English
DT Article
DE Atg5 KO; autoimmunity; B cells; inflammation; lupus; TLR7
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; GENOME-WIDE ASSOCIATION; TOLL-LIKE
RECEPTORS; VIRAL RECOGNITION; GENE ATG5; TLR7; SUSCEPTIBILITY;
PROLIFERATION; PATHOGENESIS; EXPRESSION
AB Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease, defined by loss of B cell self-tolerance that results in production of antinuclear antibodies (ANA) and chronic inflammation. While the initiating events in lupus development are not well defined, overexpression of the RNA-recognizing toll-like receptor (TLR)7 has been linked to SLE in humans and mice. We postulated that autophagy plays an essential role in TLR7 activation of B cells for the induction of SLE by delivering RNA ligands to the endosomes, where this innate immune receptor resides. To test this hypothesis, we compared SLE development in Tlr7 transgenic (Tg) mice with or without B cell-specific ablation of autophagy (Cd19-Cre Atg5(f/f)). We observed that in the absence of B cell autophagy the 2 hallmarks of SLE, ANA and inflammation, were eliminated, thus curing these mice of lupus. This was also evident in the significantly extended survival of the autophagy-deficient mice compared to Tlr7.1 Tg mice. Furthermore, glomerulonephritis was ameliorated, and the serum levels of inflammatory cytokines in the knockout (KO) mice were indistinguishable from those of control mice. These data provide direct evidence that B cells require TLR7-dependent priming through an autophagy-dependent mechanism before autoimmunity is induced, thereafter involving many cell types. Surprisingly, hyper-IgM production persisted in Tlr7.1 Tg mice in the absence of autophagy, likely involving a different activation pathway than the production of autoantibodies. Furthermore, these mice still presented with anemia, but responded with a striking increase in extramedullary hematopoiesis (EMH), possibly due to the absence of pro-inflammatory cytokines.
C1 [Weindel, Chi G.; Huber, Brigitte T.] Tufts Univ, Sackler Sch Grad Biomed Sci, Sch Med, Grad Program Genet, Boston, MA 02111 USA.
[Richey, Lauren J.] Tufts Univ, Div Lab Anim Med, Boston, MA 02111 USA.
[Bolland, Silvia] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
[Mehta, Abhiruchi J.; Huber, Brigitte T.] Tufts Univ, Sackler Sch Grad Biomed Sci, Sch Med, Dept Integrat Physiol & Pathobiol, Boston, MA 02111 USA.
[Kearney, John F.] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA.
RP Huber, BT (reprint author), Tufts Univ, Sackler Sch Grad Biomed Sci, Sch Med, Grad Program Genet, Boston, MA 02111 USA.
EM Brigitte.huber@tufts.edu
FU NIH [CTSI UL1TR001064, AI14782-36]; Division of Intramural Research,
NIAID
FX This work was supported in part by NIH CTSI UL1TR001064 (BTH), NIH
AI14782-36 (JFK) and by the Division of Intramural Research, NIAID, NIH
(SB).
NR 41
TC 9
Z9 10
U1 3
U2 14
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1554-8627
EI 1554-8635
J9 AUTOPHAGY
JI Autophagy
PD JUL
PY 2015
VL 11
IS 7
BP 1010
EP 1024
DI 10.1080/15548627.2015.1052206
PG 15
WC Cell Biology
SC Cell Biology
GA CN3CQ
UT WOS:000358301900004
PM 26120731
ER
PT J
AU Andrijauskaite, K
Suriano, S
Cloud, CA
Li, M
Kesarwani, P
Stefanik, LS
Moxley, KM
Salem, ML
Garrett-Mayer, E
Paulos, CM
Mehrotra, S
Kochenderfer, JN
Cole, DJ
Rubinstein, MP
AF Andrijauskaite, K.
Suriano, S.
Cloud, C. A.
Li, M.
Kesarwani, P.
Stefanik, L. S.
Moxley, K. M.
Salem, M. L.
Garrett-Mayer, E.
Paulos, C. M.
Mehrotra, S.
Kochenderfer, J. N.
Cole, D. J.
Rubinstein, M. P.
TI IL-12 conditioning improves retrovirally mediated transduction
efficiency of CD8(+) T cells
SO CANCER GENE THERAPY
LA English
DT Article
ID CHIMERIC ANTIGEN RECEPTOR; MURINE LEUKEMIA-VIRUS; ADOPTIVE
IMMUNOTHERAPY; GENE-THERAPY; EFFECTOR; CANCER; LYMPHOCYTES; SURVIVAL;
DISTINCT; LINEAGE
AB The ability to genetically modify T cells is a critical component to many imrnunotherapeutic strategies and research studies. However, the success of these approaches is often limited by transduction efficiency. As retrovital vectors require cell division for integration, transduction efficiency is dependent on the appropriate activation and culture Conditions for T cells. Naive CD8(+) T cells, which are quiescent, must be first activated to induce cell division to allow genetic modification. To optimize this porocess, we activated mouse T cells with a panel of different cytokines, including interleukin-2 (IL-2), IL-4, IL-6, IL-7, IL-12, IL-15 and IL-23, known to act on T cells. After activation, cytokines were removed, and activated T cells were retrovirally transduced. We found that IL-12 preconditioning of mouse T cells greatly enhanced transduction efficiency, while preserving function and expansion potential. We also observed a similar transduction-enhancing effect of IL-12 preconditicining on human T cells. These findings provide a simple method to improve the transthittion efficiencies of CD8(+) T cells.
C1 [Andrijauskaite, K.; Suriano, S.; Cloud, C. A.; Li, M.; Kesarwani, P.; Paulos, C. M.; Mehrotra, S.; Cole, D. J.; Rubinstein, M. P.] Med Univ S Carolina, Dept Surg, Charleston, SC 29425 USA.
[Stefanik, L. S.; Paulos, C. M.; Mehrotra, S.; Cole, D. J.; Rubinstein, M. P.] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA.
[Moxley, K. M.] Loyola Univ Chicago, Maywood, IL USA.
[Salem, M. L.] Tanta Univ, Fac Sci, Immunol & Biotechnol Div, Tanta, Egypt.
[Garrett-Mayer, E.] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA.
[Kochenderfer, J. N.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
RP Rubinstein, MP (reprint author), Med Univ S Carolina, Dept Surg, 86 Jonathan Lucas St,HO506, Charleston, SC 29425 USA.
EM markrubinstein@musc.edu
FU National Institutes of Health [P01CA54778-01]; National Cancer
Institute; Cell Evaluation and Therapy Shared Resource, Hollings Cancer
Center; Medical University of South Carolina [P30CA138313]; NIH Tetramer
Core Facility [HHSN272201300006C]
FX We thank Dan Neitzke for critical review of this manuscript. We thank
Gina Scurti (Loyola University) for expert technical advice in culturing
human T cells. Grant funding for this project was provided by
P01CA54778-01 from the National Institutes of Health and the National
Cancer Institute. This work was also supported in part by the Cell
Evaluation and Therapy Shared Resource, Hollings Cancer Center and
Medical University of South Carolina (P30CA138313). We also acknowledge
the NIH Tetramer Core Facility (Contract No. HHSN272201300006C) for
provision of the tetramer used in this study.
NR 45
TC 0
Z9 0
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0929-1903
EI 1476-5500
J9 CANCER GENE THER
JI Cancer Gene Ther.
PD JUL
PY 2015
VL 22
IS 7
BP 360
EP 367
DI 10.1038/cgt.2015.28
PG 8
WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity;
Medicine, Research & Experimental
SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity;
Research & Experimental Medicine
GA CN4JO
UT WOS:000358396600004
PM 26182912
ER
PT J
AU Selmansberger, M
Kaiser, JC
Hess, J
Guthlin, D
Likhtarev, I
Shpak, V
Tronko, M
Brenner, A
Abend, M
Blettner, M
Unger, K
Jacob, P
Zitzelsberger, H
AF Selmansberger, Martin
Kaiser, Jan Christian
Hess, Julia
Guethlin, Denise
Likhtarev, I.
Shpak, Victor
Tronko, Mykola
Brenner, Alina
Abend, Michael
Blettner, Maria
Unger, Kristian
Jacob, Peter
Zitzelsberger, Horst
TI Dose-dependent expression of CLIP2 in post-Chernobyl papillary thyroid
carcinomas
SO CARCINOGENESIS
LA English
DT Article
ID CANCER RISK; IONIZING-RADIATION; ACCIDENT; UKRAINE; EXPOSURE; I-131;
SIGNATURE; RECONSTRUCTION; REARRANGEMENTS; CHILDREN
AB This study showed a clear dose-response relationship for the CLIP2 radiation marker in post-Chernobyl papillary thyroid carcinoma cohorts for young patients and hints to different molecular mechanisms in tumors induced at low doses compared to moderate/high doses.A previous study on papillary thyroid carcinomas (PTC) in young patients who were exposed to (131)iodine from the Chernobyl fallout revealed an exclusive gain of chromosomal band 7q11.23 in exposed cases compared to an age-matched control cohort. CLIP2, a gene located within band 7q11.23 was shown to be differentially expressed between exposed and non-exposed cases at messenger RNA and protein level. Therefore, a standardized procedure for CLIP2 typing of PTCs has been developed in a follow-up study. Here we used CLIP2 typing data on 117 post-Chernobyl PTCs from two cohorts of exposed patients with individual dose estimates and 24 non-exposed controls to investigate a possible quantitative dose-response relationship of the CLIP2 marker. The 'Genrisk-T' cohort consisted of 45 PTCs and the 'UkrAm' cohort of 72 PTCs. Both cohorts differed in mean dose (0.59 Gy Genrisk-T, 1.2 Gy UkrAm) and mean age at exposure (AaE) (2 years Genrisk-T, 8 years UkrAm), whilst the median latency (16 years Genrisk-T, 18 years UkrAm) was comparable. We analyzed the association between the binary CLIP2 typing and continuous thyroid dose with logistic regression. A clear positive dose-response relationship was found for young PTC cases [age at operation (AaO) < 20 years, AaE < 5 years]. In the elder age group a higher proportion of sporadic tumors is assumed due to a negligible dose response, suggesting different molecular mechanisms in sporadic and radiation-induced cases. This is further supported by the association of elder patients (AaO > 20 years) with positivity for BRAF V600E mutation.
C1 [Selmansberger, Martin; Hess, Julia; Unger, Kristian; Zitzelsberger, Horst] German Res Ctr Environm Hlth GmbH, Res Unit Radiat Cytogenet, D-85674 Neuherberg, Germany.
[Kaiser, Jan Christian; Guethlin, Denise; Jacob, Peter] German Res Ctr Environm Hlth GmbH, Helmholtz Zentrum Munchen, Inst Radiat Protect, D-85674 Neuherberg, Germany.
[Likhtarev, I.] Ukrainian Acad Technol Sci, Radiat Protect Inst, UA-04050 Kiev, Ukraine.
[Shpak, Victor; Tronko, Mykola] Natl Acad Med Sci Ukraine, Inst Endocrinol & Metab, UA-254114 Kiev, Ukraine.
[Brenner, Alina] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Abend, Michael] Bundeswehr Inst Radiobiol, D-80937 Munich, Germany.
[Blettner, Maria] Johannes Gutenberg Univ Mainz, Inst Med Biometrie Epidemiol & Informat IMBEI, D-55131 Mainz, Germany.
RP Kaiser, JC (reprint author), German Res Ctr Environm Hlth GmbH, Helmholtz Zentrum Munchen, Inst Radiat Protect, D-85674 Neuherberg, Germany.
EM christian.kaiser@helmholtz-muenchen.de
OI HeSS, Julia/0000-0001-9860-1426; Unger, Kristian/0000-0002-0374-2320;
Kaiser, Jan Christian/0000-0003-0359-2251
FU European Commission, EpiRadBio project, FP7 [269553]
FX This study was supported by the European Commission, EpiRadBio project,
FP7 grant no. 269553.
NR 35
TC 5
Z9 6
U1 1
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0143-3334
EI 1460-2180
J9 CARCINOGENESIS
JI Carcinogenesis
PD JUL
PY 2015
VL 36
IS 7
BP 748
EP 756
DI 10.1093/carcin/bgv043
PG 9
WC Oncology
SC Oncology
GA CN1JN
UT WOS:000358175700006
PM 25957251
ER
PT J
AU Noureddin, M
Rotman, Y
Zhang, F
Park, H
Rehermann, B
Thomas, E
Liang, TJ
AF Noureddin, M.
Rotman, Y.
Zhang, F.
Park, H.
Rehermann, B.
Thomas, E.
Liang, T. J.
TI Hepatic expression levels of interferons and interferon-stimulated genes
in patients with chronic hepatitis C: A phenotype-genotype correlation
study
SO GENES AND IMMUNITY
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; VIRUS-INFECTION; INTERLEUKIN 28B; VIRAL
CLEARANCE; IL28B GENOTYPE; THERAPY; ALPHA; RIBAVIRIN; SOFOSBUVIR;
KINETICS
AB IFNL4 is linked to hepatitis C virus treatment response and type III interferons (IFNs). We studied the functional associations among hepatic expressions of IFNs and IFN-stimulated genes (ISGs), and treatment response to peginterferon and ribavirin. Type I IFNs (IFNA1, IFNB1), type II (IFNG), type III (IFNL1, IFNL2/3), IFNL4 and ISG hepatic expressions were measured by qPCR from in 65 chronic hepatitis C (CHC) patients whose IFNL4-associated rs368234815 and IFNL3-associated rs12989760 genotype were determined. There was a robust correlation of hepatic expression within type I and type III IFNs and between type III IFNs and IFNL4 but no correlation between other IFN types. Expression of ISGs correlated with type III IFNs and IFNL4 but not with type I IFNs. Levels of ISGs and IFNL2/3 mRNAs were lower in IFNL3 rs12979860 CC patients compared with non-CC patients, and in treatment responders, compared with nonresponders. IFNL4-Delta G genotype was associated with high ISG levels and nonresponse. Hepatic levels of ISGs in CHC are associated with IFNL2/3 and IFNL4 expression, suggesting that IFNLs, not other types of IFNs, drive ISG expression. Hepatic IFNL2/3 expression is functionally linked to IFNL4 and IFNL3 polymorphisms, potentially explaining the tight association among ISG expression and treatment response.
C1 [Noureddin, M.; Rotman, Y.; Zhang, F.; Park, H.; Rehermann, B.; Thomas, E.; Liang, T. J.] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
[Noureddin, M.] Cedars Sinai Med Ctr, Div Gastroenterol, Los Angeles, CA 90048 USA.
[Park, H.; Rehermann, B.] NIDDK, Immunol Sect, NIH, Bethesda, MD 20892 USA.
RP Liang, TJ (reprint author), NIDDK, Liver Dis Branch, NIH, Bldg 10,Room 9B-16,10 Ctr Dr,MSC 1800, Bethesda, MD 20892 USA.
EM jakel@bdg10.niddk.nih.gov
FU Intramural Research Program of the NIDDK, NIH
FX This research was supported by the Intramural Research Program of the
NIDDK, NIH.
NR 38
TC 7
Z9 7
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1466-4879
EI 1476-5470
J9 GENES IMMUN
JI Genes Immun.
PD JUL-AUG
PY 2015
VL 16
IS 5
BP 321
EP 329
DI 10.1038/gene.2015.11
PG 9
WC Genetics & Heredity; Immunology
SC Genetics & Heredity; Immunology
GA CN4CC
UT WOS:000358375500005
PM 26020282
ER
PT J
AU Muhie, S
Hammamieh, R
Cummings, C
Yang, D
Jett, M
AF Muhie, S.
Hammamieh, R.
Cummings, C.
Yang, D.
Jett, M.
TI Stress-caused anergy of leukocytes towards Staphylococcal enterotoxin B
and exposure transcriptome signatures
SO GENES AND IMMUNITY
LA English
DT Article
ID T-CELL-RECEPTOR; CYTOKINE PRODUCTION; IMMUNE SUPPRESSION;
GENE-EXPRESSION; TOXIC-SHOCK; IN-VITRO; SUPERANTIGEN; ACTIVATION;
INFLAMMATION; MECHANISM
AB Leucocytes from soldiers exposed to battlefield-like stress (RASP: Rangers Assessment and Selection Program) were exposed in vitro to Staphylococcal enterotoxin B (SEB). We assayed SEB-induced regulation of gene expression, both in the presence and absence of severe stress, to generate two sets of gene profiles. One set of transcripts and microRNAs were specific to post-RASP SEB exposure, and another set were signatures of SEB exposure common to both the pre-and post-RASP leucocytes. Pathways and upstream regulatory analyses indicated that the post-RASP SEB-signature transcripts were manifestation of the anergic state of post-RASP leucocytes. These were further verified using expression-based predictions of cellular processes and literature searches. Specificity of the second set of transcripts to SEB exposure was verified using machine-learning algorithms on our and four other (Gene Expression Omnibus) data sets. Cell adhesion, coagulation, hypoxia and vascular endothelial growth factor-mediated vascular leakage were SEB-specific pathways even under the background of severe stress. Hsa-miR-155-3p was the top SEB exposure predictor in our data set, and C-X-C motif chemokine ligand 9 was SEB specific in all the analyzed data sets. The SEB-signature transcripts (which also showed distinct expression signatures from Yersinia pestis and dengue virus) may serve as potential biomarkers of SEB exposure even under the background of stress.
C1 [Muhie, S.] Frederick Natl Lab Canc Res, Adv Biomed Comp Ctr, Frederick, MD USA.
[Hammamieh, R.; Jett, M.] US Army, Integrat Syst Biol Program, Ctr Environm Hlth Res, Frederick, MD 21702 USA.
[Yang, D.] Georgetown Univ, Dept Chem, Washington, DC 20057 USA.
RP Jett, M (reprint author), US Army, Integrat Syst Biol Program, Ctr Environm Hlth Res, Frederick, MD 21702 USA.
EM marti.jett-tilton.civ@mail.mil
FU Defense Threat Reduction Agency
FX We thank Julia Scheerer and Allison Hoke for editing the manuscript and
for their invaluable comments. We are grateful to The Defense Threat
Reduction Agency for funding.
NR 30
TC 0
Z9 0
U1 1
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1466-4879
EI 1476-5470
J9 GENES IMMUN
JI Genes Immun.
PD JUL-AUG
PY 2015
VL 16
IS 5
BP 330
EP 346
DI 10.1038/gene.2015.16
PG 17
WC Genetics & Heredity; Immunology
SC Genetics & Heredity; Immunology
GA CN4CC
UT WOS:000358375500006
PM 26020283
ER
PT J
AU King, SB
Lederman, RJ
AF King, Spencer B., III
Lederman, Robert J.
TI Lost in Translation
SO JACC-CARDIOVASCULAR INTERVENTIONS
LA English
DT Editorial Material
ID AORTIC ACCESS
C1 [Lederman, Robert J.] NHLBI, Bethesda, MD 20892 USA.
RP King, SB (reprint author), St Josephs Heart & Vasc Inst, 5665 Peachtree Dunwoody Rd NE, Atlanta, GA 30342 USA.
EM spencer.king@emoryhealthcare.org
OI lederman, robert/0000-0003-1202-6673
FU Intramural NIH HHS [ZIA HL006040-06, ZIA HL005062-13]
NR 4
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 1936-8798
EI 1876-7605
J9 JACC-CARDIOVASC INTE
JI JACC-Cardiovasc. Interv.
PD JUL
PY 2015
VL 8
IS 8
BP 1138
EP 1139
DI 10.1016/j.jcin.2015.06.005
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CN2OK
UT WOS:000358261300031
PM 26205455
ER
PT J
AU Cruickshanks, KJ
Dhar, S
Dinces, E
Fifer, RC
Gonzalez, F
Heiss, G
Hoffman, HJ
Lee, DJ
Newhoff, M
Tocci, L
Torre, P
Tweed, TS
AF Cruickshanks, Karen J.
Dhar, Sumitrajit
Dinces, Elizabeth
Fifer, Robert C.
Gonzalez, Franklyn, II
Heiss, Gerardo
Hoffman, Howard J.
Lee, David J.
Newhoff, Marilyn
Tocci, Laura
Torre, Peter, III
Tweed, Ted S.
TI Hearing Impairment Prevalence and Associated Risk Factors in the
Hispanic Community Health Study/Study of Latinos
SO JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY
LA English
DT Article
ID NUTRITION EXAMINATION SURVEY; QUALITY-OF-LIFE; OLDER-ADULTS;
NATIONAL-HEALTH; BEAVER-DAM; AID USE; CUMULATIVE INCIDENCE; DIVERSE
BACKGROUNDS; GLOBAL BURDEN; UNITED-STATES
AB IMPORTANCE Hearing impairment is common in adults, but few studies have addressed it in the US Hispanic/Latino population.
OBJECTIVE To determine the prevalence of hearing impairment among US Hispanic/Latino adults of diverse backgrounds and determine associations with potential risk factors.
DESIGN, SETTING, AND PARTICIPANTS The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) is a population-based sample of Hispanics/Latinos in four US communities (Bronx, New York; Chicago, Illinois; Miami, Florida; and San Diego, California). Examinations were conducted from 2008 through 2011. The HCHS/SOL examined 16 415 self-identified Hispanic/Latino persons aged 18 to 74 years recruited from randomly selected households using a stratified 2-stage area probability sample design based on census block groups and households within block groups.
MAIN OUTCOMES AND MEASURES Hearing thresholdswere measured by pure-tone audiometry. Hearing impairment was defined as a pure-tone average (PTA) of thresholds at 0.5, 1, 2, and 4 kHz greater than 25 dB hearing level. Bilateral hearing impairment required a PTA greater than 25 dB hearing level in both ears. Multivariable analyses included adjustments for sociodemographic and lifestyle variables, body mass index, and medical conditions.
RESULTS The prevalence of hearing impairment was 15.06%(SE, 0.44%) overall, and 8.24% (SE, 0.33%) had bilateral hearing impairment. The prevalence of hearing impairment was higher among people 45 years and older, ranging by Hispanic/Latino background from 29.35% to 41.20% among men and 17.89% to 32.11% among women. The multivariable-adjusted odds of hearing impairment was greater for participants of Puerto Rican background compared with Mexican background (odds ratio [OR], 1.57 [95% CI, 1.10-2.25]). The odds of hearing impairment were lower with more education (OR, 0.71 [95% CI, 0.59-0.86] for at least high school) and higher income (OR, 0.58 [95% CI, 0.36-0.92] for >$75 000 vs <=$ 10 000). Noise exposure (OR, 1.35 [95% CI, 1.07-1.70]), diabetes (OR, 1.57 [95% CI, 1.27-1.94]), and prediabetes (OR, 1.37 [95% CI, 1.12-1.67]) were associated with hearing impairment.
CONCLUSIONS AND RELEVANCE Hearing impairment is a common problem for older Hispanics/Latinos in these communities and is associated with socioeconomic factors, noise exposure, and abnormal glucose metabolism. Longitudinal studies are needed to determine whether these factors are involved in the etiology of hearing impairment and to identify ways to prevent or delay age-related changes in hearing.
C1 [Cruickshanks, Karen J.; Tweed, Ted S.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI 53705 USA.
[Cruickshanks, Karen J.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI 53705 USA.
[Dhar, Sumitrajit] Northwestern Univ, Roxelyn & Richard Pepper Dept Commun Sci & Disord, Evanston, IL USA.
[Dinces, Elizabeth; Tocci, Laura] Univ Hosp, Albert Einstein Coll Med, Montefiore Med Ctr, Dept Otorhinolaryngol Head & Neck Surg, Bronx, NY USA.
[Fifer, Robert C.] Univ Miami, Miller Sch Med, Dept Pediat, Mailman Ctr Child Dev, Miami, FL 33136 USA.
[Gonzalez, Franklyn, II; Heiss, Gerardo] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Biostat, Collaborat Studies Coordinating Ctr, Chapel Hill, NC USA.
[Hoffman, Howard J.] Natl Inst Deafness & Other Commun Disorders, Epidemiol & Stat Program, NIH, Bethesda, MD USA.
[Lee, David J.] Univ Miami, Miller Sch Med, Dept Publ Hlth Sci, Miami, FL 33136 USA.
[Newhoff, Marilyn] San Diego State Univ, Coll Hlth & Human Serv, San Diego, CA 92182 USA.
[Newhoff, Marilyn; Torre, Peter, III] San Diego State Univ, Sch Speech Language & Hearing Sci, San Diego, CA 92182 USA.
RP Cruickshanks, KJ (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, 610 Walnut St,10th Floor WARF, Madison, WI 53705 USA.
EM cruickshanks@episense.wisc.edu
FU National Heart, Lung, and Blood Institute [NO1-HC65233, NO1-HC65234,
NO1-HC65235, NO1-HC65236, NO1-HC65237]; National Institute on Deafness
and Other Communication Disorders, National Institutes of Health;
National Heart, Lung, and Blood Institute: National Center on Minority
Health and Health Disparities; National Institute on Deafness and Other
Communications Disorders; National Institute of Dental and Craniofacial
Research; National Institute of Diabetes and Digestive and Kidney
Diseases; National Institute of Neurological Disorders and Stroke;
Office of Dietary Supplements
FX The Hispanic Community Health Study/Study of Latinos was carried out as
a collaborative study supported by contracts from the National Heart,
Lung, and Blood Institute to the University of North Carolina
(NO1-HC65233), University of Miami (NO1-HC65234), Albert Einstein
College of Medicine (NO1-HC65235), Northwestern University
(NO1-HC65236), and San Diego State University (NO1-HC65237). The hearing
protocol and Hearing Reading Center were sponsored and funded as an
adjunct to HCSH/SOL through Intra-Agency Agreement with the National
Institute on Deafness and Other Communication Disorders, National
Institutes of Health. In addition, the following institutes, centers, or
offices contributed to specific components in the protocol and, also, to
the overall collection of data in the HCHS/SOL through a transfer of
funds to the National Heart, Lung, and Blood Institute: National Center
on Minority Health and Health Disparities, the National Institute on
Deafness and Other Communications Disorders, the National Institute of
Dental and Craniofacial Research, the National Institute of Diabetes and
Digestive and Kidney Diseases, the National Institute of Neurological
Disorders and Stroke, and the Office of Dietary Supplements.
NR 44
TC 2
Z9 3
U1 1
U2 3
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6181
EI 2168-619X
J9 JAMA OTOLARYNGOL
JI JAMA Otolaryngol-Head Neck Surg.
PD JUL
PY 2015
VL 141
IS 7
BP 641
EP 648
DI 10.1001/jamaoto.2015.0889
PG 8
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA CN0DB
UT WOS:000358081900009
PM 26021283
ER
PT J
AU Lee, J
Joo, K
Brooks, BR
Lee, J
AF Lee, Juyong
Joo, Keehyoung
Brooks, Bernard R.
Lee, Jooyoung
TI The Atomistic Mechanism of Conformational Transition of Adenylate Kinase
Investigated by Lorentzian Structure-Based Potential
SO JOURNAL OF CHEMICAL THEORY AND COMPUTATION
LA English
DT Article
ID MOLECULAR-DYNAMICS; NETWORK MODEL; GLOBAL OPTIMIZATION;
SUBSTRATE-BINDING; ENERGY LANDSCAPE; NUCLEIC-ACIDS; PROTEINS; CATALYSIS;
MOTIONS; PREDICTION
AB We present a new all-atom structure-based method to study protein conformational transitions using Lorentzian attractive interactions based on native structures. The variability of each native contact is estimated based on evolutionary information using a machine learning method. To test the validity of this approach, we have investigated the conformational transition of adenylate kinase (ADK). The intrinsic boundedness of the Lorentzian attractive interactions facilitated frequent conformational transitions, and consequently we were able to observe more than 1000 structural interconversions between the open and closed states of ADK out of a total of 6 mu s MD simulations. ADK has three domains: the nucleoside monophosphate (NMP) binding domain, the LID-domain, and the CORE domain, which catalyze the interconversion between ATP and ADP. We identified two transition states: a more frequent LID-closed-NMP-open (TS1) state and a less frequent LID-open-NMP-closed (TS2) state. The transition was found to be symmetric in both directions via TS1. We also obtained an off-pathway metastable state that was previously observed with physics-based all-atom simulations but not with coarse-grained models. In the metastable state, the LID domain was slightly twisted and formed contacts with the NMP domain. Our model correctly identified a total of 14 out of the top 16 residues with highest fluctuation by NMR experiment, thus showing excellent agreement with experimental NMR relaxation data and overwhelmingly better results than existing models.
C1 [Lee, Juyong; Lee, Jooyoung] Korea Inst Adv Study, Sch Computat Sci, Seoul 130722, South Korea.
[Lee, Juyong; Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20852 USA.
[Joo, Keehyoung; Lee, Jooyoung] Korea Inst Adv Study, Ctr Silico Prot Sci, Seoul 130722, South Korea.
[Joo, Keehyoung] Korea Inst Adv Study, Ctr Adv Computat, Seoul 130722, South Korea.
RP Lee, J (reprint author), Korea Inst Adv Study, Sch Computat Sci, Seoul 130722, South Korea.
EM jlee@kias.re.kr
RI Lee, Juyong/A-7869-2013
OI Lee, Juyong/0000-0003-1174-4358
FU National Research Foundation of Korea (NRF) - Korea government (MEST)
[2008-0061987]; KISTI Supercomputing Center [KSC-2012-C3-01]
FX We thank Masaki Sasai, Kunihiro Kuwajima, Yanwen Tan, and Steven Gross
for helpful discussions. We thank Katherine Henzler-Wildman and Dorothee
Kern for kindly providing the NMR relaxation data. This work was
supported by the National Research Foundation of Korea (NRF) grant
funded by the Korea government (MEST) (No. 2008-0061987). We thank Korea
Institute for Advanced Study for providing computing resources (KIAS
Center for Advanced Computation Linux Cluster) for this work. We also
would like to acknowledge the support from the KISTI Supercomputing
Center (KSC-2012-C3-01).
NR 75
TC 3
Z9 3
U1 1
U2 8
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1549-9618
EI 1549-9626
J9 J CHEM THEORY COMPUT
JI J. Chem. Theory Comput.
PD JUL
PY 2015
VL 11
IS 7
BP 3211
EP 3224
DI 10.1021/acs.jctc.5b00268
PG 14
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA CN0LJ
UT WOS:000358104800032
PM 26575758
ER
PT J
AU Cohen, JI
Niemela, JE
Stoddard, JL
Pittaluga, S
Heslop, H
Jaffe, ES
Dowdell, K
AF Cohen, Jeffrey I.
Niemela, Julie E.
Stoddard, Jennifer L.
Pittaluga, Stefania
Heslop, Helen
Jaffe, Elaine S.
Dowdell, Kennichi
TI Late-Onset Severe Chronic Active EBV in a Patient for Five Years with
Mutations in STXBP2 (MUNC18-2) and PRF1 (Perforin 1)
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Article
DE Epstein-Barr virus; chronic active Epstein-Barr virus; MUNC18-2; STXBP2;
perforin 1
ID FAMILIAL HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS; BARR-VIRUS INFECTION;
CLINICAL PRESENTATIONS; SPECTRUM; CHILDREN; DEFECTS; BINDING; DISEASE;
IMPAIR; A91V
AB Severe chronic active Epstein-Barr virus (CAEBV) disease is defined as a severe progressive illness lasting 6 months or longer with infiltration of tissues with EBV-positive lymphocytes, markedly elevated levels of EBV DNA in the blood, and no known immunodeficiency such as HIV. These patients usually have fever, splenomegaly, lymphadenopathy, and may have markedly elevated EBV antibody titers to viral capsid antigen. Although the cause of most cases of severe CAEBV is unknown, one well-documented case was associated with compound heterozygous mutations in PRF1 (perforin 1). Here we report a patient with prolonged severe CAEBV who underwent bone marrow transplant for his disease and subsequently was found to have compound heterozygous mutations in STXBP2 (MUNC18-2) as well as a heterozygous mutation in PRF1 (perforin 1).
C1 [Cohen, Jeffrey I.; Dowdell, Kennichi] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Niemela, Julie E.; Stoddard, Jennifer L.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
[Pittaluga, Stefania; Jaffe, Elaine S.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Heslop, Helen] Baylor Coll Med, Methodist Hosp, Ctr Cell & Gene Therapy, Houston, TX 77030 USA.
[Heslop, Helen] Texas Childrens Hosp, Houston, TX 77030 USA.
RP Cohen, JI (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
EM jcohen@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases
FX This work was supported by the intramural research program of the
National Institute of Allergy and Infectious Diseases.
NR 16
TC 3
Z9 4
U1 2
U2 6
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
EI 1573-2592
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD JUL
PY 2015
VL 35
IS 5
BP 445
EP 448
DI 10.1007/s10875-015-0168-y
PG 4
WC Immunology
SC Immunology
GA CN1RA
UT WOS:000358196300003
PM 25947952
ER
PT J
AU Hsu, AP
Pittaluga, S
Martinez, B
Rump, AP
Raffeld, M
Uzel, G
Puck, JM
Freeman, AF
Holland, SM
AF Hsu, Amy P.
Pittaluga, Stefania
Martinez, Bianca
Rump, Amy P.
Raffeld, Mark
Uzel, Gulbu
Puck, Jennifer M.
Freeman, Alexandra F.
Holland, Steven M.
TI IL2RG Reversion Event in a Common Lymphoid Progenitor Leads to Delayed
Diagnosis and Milder Phenotype
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Article
DE X-SCID; IL2RG; Reversion; Common gamma chain
ID SEVERE COMBINED IMMUNODEFICIENCY; INTERLEUKIN-2-RECEPTOR GAMMA-CHAIN;
RECEPTOR EXCISION CIRCLES; FUNCTIONAL COMPONENT; IN-VIVO;
DIFFERENTIATION; MUTATION; CELLS; IL-21
AB Severe combined immunodeficiency (SCID) is most frequently caused by mutations in the cytokine receptor common gamma chain, CD132, encoded by the X-linked gene, IL2RG. Most patients present in the first year of life with failure to thrive, severe, opportunistic infections and absence of CD3+ T cells. We present a patient with pediatric illness and a diagnosis of combined variable immune deficiency (CVID) who was diagnosed at age 23 with an inherited IL2RG mutation causing loss of signal transduction through CD132. His peripheral blood included CD3/CD4 and CD3/CD8 positive cells as well as low levels of CD19+ B cells containing a reversion to the wildtype IL2RG allele. The reversion, which was not present at birth, may account for his mild phenotype and late diagnosis.
C1 [Hsu, Amy P.; Martinez, Bianca; Uzel, Gulbu; Freeman, Alexandra F.; Holland, Steven M.] NIAID, NIH, Lab Clin Infect Dis, Bethesda, MD 20892 USA.
[Pittaluga, Stefania; Raffeld, Mark] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Rump, Amy P.] Leidos Biomed Res Inc, Clin Res Directorate, Clin Monitoring Res Program, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Puck, Jennifer M.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA.
RP Holland, SM (reprint author), NIAID, NIH, Lab Clin Infect Dis, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM smh@nih.gov
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health, USA; National Cancer
Institute, National Institutes of Health [HHSN261200800001E]
FX The views expressed in this article are those of the authors and do not
reflect the official policy of the U.S. Government. This research was
supported in part by the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health, USA. This project has been funded in part with federal funds
from the National Cancer Institute, National Institutes of Health, under
Contract No. HHSN261200800001E.
NR 18
TC 1
Z9 1
U1 2
U2 6
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
EI 1573-2592
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD JUL
PY 2015
VL 35
IS 5
BP 449
EP 453
DI 10.1007/s10875-015-0174-0
PG 5
WC Immunology
SC Immunology
GA CN1RA
UT WOS:000358196300004
PM 26076747
ER
PT J
AU Weathers, SP
Gilbert, MR
AF Weathers, Shiao-Pei
Gilbert, Mark R.
TI Current challenges in designing GBM trials for immunotherapy
SO JOURNAL OF NEURO-ONCOLOGY
LA English
DT Editorial Material
DE Glioblastoma; Immunotherapy; Vaccines; Immune checkpoint inhibitors;
Virotherapy
ID NEWLY-DIAGNOSED GLIOBLASTOMA; METASTATIC MELANOMA; T-CELLS;
IMMUNE-RESPONSES; MALIGNANT GLIOMA; BRAIN-TUMORS; IPILIMUMAB; GROWTH;
CANCER; SURVIVAL
AB Immune system modulation is evolving into a promising treatment modality in glioblastoma. Our growing understanding of glioma immunobiology has fueled efforts to develop immunotherapeutic strategies to combat this lethal primary brain tumor. Autologous stimulated lymphocytes, immunotherapy with cytokines and dendritic cells, immune checkpoint inhibitors, virotherapy, and tumor or peptide based vaccines are immunotherapy approaches under active investigation. A number of challenges are evident in the design of immunotherapy clinical trials in glioblastoma including patient selection, immune and imaging response monitoring, and evaluation of clinical outcome.
C1 [Weathers, Shiao-Pei] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Unit 431, Houston, TX 77030 USA.
[Gilbert, Mark R.] NCI, Neurooncol Branch, NIH, Bethesda, MD 20892 USA.
RP Weathers, SP (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Unit 431, 1515 Holcombe Blvd, Houston, TX 77030 USA.
EM sweathers@mdanderson.org; mark.gilbert@nih.gov
RI Gilbert, Mark/J-7494-2016
OI Gilbert, Mark/0000-0003-2556-9722
NR 55
TC 6
Z9 6
U1 1
U2 8
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-594X
EI 1573-7373
J9 J NEURO-ONCOL
JI J. Neuro-Oncol.
PD JUL
PY 2015
VL 123
IS 3
SI SI
BP 331
EP 337
DI 10.1007/s11060-015-1716-2
PG 7
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA CN1EM
UT WOS:000358160000003
PM 25577401
ER
PT J
AU Teckman, JH
Rosenthal, P
Abel, R
Bass, LM
Michail, S
Murray, KF
Rudnick, DA
Thomas, DW
Spino, C
Arnon, R
Hertel, PM
Heubi, J
Kamath, BM
Karnsakul, W
Loomes, KM
Magee, JC
Molleston, JP
Romero, R
Shneider, BL
Sherker, AH
Sokol, RJ
AF Teckman, Jeffrey H.
Rosenthal, Philip
Abel, Robert
Bass, Lee M.
Michail, Sonia
Murray, Karen F.
Rudnick, David A.
Thomas, Daniel W.
Spino, Cathie
Arnon, Ronen
Hertel, Paula M.
Heubi, James
Kamath, Binita M.
Karnsakul, Wikrom
Loomes, Kathleen M.
Magee, John C.
Molleston, Jean P.
Romero, Rene
Shneider, Benjamin L.
Sherker, Averell H.
Sokol, Ronald J.
CA Childhood Liver Dis Res Network
TI Baseline Analysis of a Young alpha-1-Antitrypsin Deficiency Liver
Disease Cohort Reveals Frequent Portal Hypertension
SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION
LA English
DT Article
DE cirrhosis; jaundice; liver enzymes; liver transplant; metabolic liver
disease
ID ALPHA1-ANTITRYPSIN DEFICIENCY; MURINE MODEL; CHILDREN; INFANTS; ADULTS;
DAMAGE
AB Objectives:-1-Antitrypsin (A1AT) deficiency is a common genetic disease with an unpredictable and highly variable course. The Childhood Liver Disease Research and Education Network is a National Institutes of Health, multicenter, longitudinal consortium studying pediatric liver diseases, with the objective of prospectively defining natural history and identifying disease modifiers.Methods:Longitudinal, cohort study of A1AT patients' birth through 25 years diagnosed as having liver disease, type PIZZ or PISZ. Medical history, physical examination, laboratory, imaging, and standardized survey tool data were collected during the provision of standard of care.Results:In the present report of the cohort at baseline, 269 subjects were enrolled between November 2008 and October 2012 (208 with their native livers and 61 postliver transplant). Subjects with mild disease (native livers and no portal hypertension [PHT]) compared to severe disease (with PHT or postliver transplant) were not different in age at presentation. A total of 57% of subjects with mild disease and 76% with severe disease were jaundiced at presentation (P=0.0024). A total of 29% of subjects with native livers had PHT, but age at diagnosis and growth were not different between the no-PHT and PHT groups (P>0.05). Subjects with native livers and PHT were more likely to have elevated bilirubin, ALT, AST, INR, and GGTP than the no-PHT group (P<<0.001), but overlap was large. Chemistries alone could not identify PHT.Conclusions:Many subjects with A1AT presenting with elevated liver tests and jaundice improve spontaneously. Subjects with PHT have few symptoms and normal growth. Longitudinal cohort follow-up will identify genetic and environmental disease modifiers.
C1 [Teckman, Jeffrey H.] St Louis Univ, Cardinal Glennon Childrens Med Ctr, Pediat & Biochem, St Louis, MO 63104 USA.
[Rosenthal, Philip; Spino, Cathie] Univ Calif San Francisco, Pediat & Surg, San Francisco, CA 94143 USA.
[Abel, Robert] Univ Michigan, Biostat, Ann Arbor, MI 48109 USA.
[Bass, Lee M.] Northwestern Univ, Feinberg Sch Med, Pediat, Chicago, IL 60611 USA.
[Michail, Sonia; Thomas, Daniel W.] Childrens Hosp Los Angeles, Pediat Gastroenterol Hepatol & Nutr, Los Angeles, CA 90027 USA.
[Murray, Karen F.] Seattle Childrens Hosp, Pediat Gastroenterol & Hepatol, Seattle, WA USA.
[Rudnick, David A.] Washington Univ, Pediat, St Louis, MO USA.
[Arnon, Ronen] Mt Sinai Sch Med, Pediat, New York, NY USA.
[Hertel, Paula M.] Texas Childrens Hosp, Baylor Coll Med, Pediat, Houston, TX 77030 USA.
[Heubi, James] Childrens Hosp Med Ctr, Pediat Gastroenterol & Hepatol, Cincinnati, OH USA.
[Kamath, Binita M.] Hosp Sick Children, Pediat Gastroenterol Hepatol & Nutr, Toronto, ON M5G 1X8, Canada.
[Karnsakul, Wikrom] Johns Hopkins Univ, Sch Med, Pediat, Baltimore, MD USA.
[Loomes, Kathleen M.] Childrens Hosp Philadelphia, Pediat Gastroenterol Hepatol & Nutr, Philadelphia, PA 19104 USA.
[Magee, John C.] Univ Michigan, Sch Med, Surg, Ann Arbor, MI USA.
[Molleston, Jean P.] James Whitcomb Riley Hosp Children, Pediat Gastroenterol Hepatol & Nutr, Indianapolis, IN 46202 USA.
[Romero, Rene] Emory Univ, Childrens Healthcare Atlanta, Pediat, Atlanta, GA 30322 USA.
[Shneider, Benjamin L.] Univ Pittsburgh, Pediat, Pittsburgh, PA USA.
[Sherker, Averell H.] NIDDK, NIH, Baltimore, MD USA.
[Sokol, Ronald J.] Univ Colorado, Childrens Hosp Colorado, Pediat Gastroenterol, Aurora, CO USA.
RP Teckman, JH (reprint author), St Louis Univ, Sch Med, Pediat & Biochem & Mol Biol, 1465 S Grand Blvd, St Louis, MO 63104 USA.
EM teckmanj@slu.edu
FU Alpha-1 Foundation (University of Colorado Denver); National Institute
of Diabetes, Digestive and Kidney Diseases; National Center for
Advancing Translational Sciences (NCATS) [DK 62445, DK 62497, UL1
TR000077, DK 62470, DK 62481, UL1 TR000003, DK 62456, DK 84536, UL1
TR000006, DK 84575]; Alpha-1 Foundation (Saint Louis University School
of Medicine); The National Center for Advancing Translational Sciences
(NCATS) [UL1 TR000423, DK 62500, UL1 TR000004, DK 62503, UL1 TR000424,
DK 62466, UL1 UL1 TR000005, DK 62453, UL1 000154, DK 62452, UL1
TR000448, DK 84538, UL1 TR000130, DK 62436, UL1 TR000150]
FX This work was supported by funding from the Alpha-1 Foundation
(University of Colorado Denver and Saint Louis University School of
Medicine) and by U01 grants from the National Institute of Diabetes,
Digestive and Kidney Diseases and from the National Center for Advancing
Translational Sciences (NCATS) UL1 grants: DK 62445 (Mt. Sinai School of
Medicine), DK 62497 and UL1 TR000077 (Cincinnati Children's Hospital
Medical Center, University of Cincinnati), DK 62470 (Baylor College of
Medicine) DK 62470 (Children's Healthcare of Atlanta, Emory University),
DK 62481 and UL1 TR000003 (The Children's Hospital of Philadelphia,
University of Pennsylvania), DK 62456 (University of Michigan), DK 84536
and UL1 TR000006 (Riley Hospital for Children, Indiana University), DK
84575 and UL1 TR000423 (Seattle Children's Hospital, University of
Washington), DK 62500 and UL1 TR000004 (UCSF Children's Hospital,
University of California San Francisco), DK 62503 and UL1 TR000424
(Johns Hopkins School of Medicine), DK 62466 and UL1 UL1 TR000005
(Children's Hospital of Pittsburgh, University of Pittsburgh), DK 62453
and UL1 000154 (University of Colorado Denver, The Children's Hospital
Denver), DK 62452 and UL1 TR000448 (Washington University School of
Medicine, St. Louis, St. Louis Children's Hospital), DK 84538 and UL1
TR000130 (Children's Hospital Los Angeles, University of Southern
California), DK 62436 and UL1 TR000150 (Ann and Robert H. Lurie
Children's Hospital of Chicago, Northwestern University).
NR 20
TC 2
Z9 2
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0277-2116
EI 1536-4801
J9 J PEDIATR GASTR NUTR
JI J. Pediatr. Gastroenterol. Nutr.
PD JUL
PY 2015
VL 61
IS 1
BP 94
EP 101
DI 10.1097/MPG.0000000000000753
PG 8
WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics
SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics
GA CN1HC
UT WOS:000358168300016
PM 25651489
ER
PT J
AU Lee, SM
Romero, R
Park, JS
Chaemsaithong, P
Jun, JK
Yoon, BH
AF Lee, Seung Mi
Romero, Roberto
Park, Joong Shin
Chaemsaithong, Piya
Jun, Jong Kwan
Yoon, Bo Hyun
TI A transcervical amniotic fluid collector: a new medical device for the
assessment of amniotic fluid in patients with ruptured membranes
SO JOURNAL OF PERINATAL MEDICINE
LA English
DT Article
DE Amniocentesis; alpha-fetoprotein; beta-human chorionic gonadotrophin;
premature rupture of membranes; prolactin; PROM; pPROM; transcervical
amniotic fluid collector; Yoon's AF Collector (TM)
ID PRETERM PREMATURE RUPTURE; LECITHIN-SPHINGOMYELIN RATIO; BLOOD-CELL
COUNT; PRELABOR RUPTURE; VAGINAL FLUID; INTRAAMNIOTIC INFECTION;
PROTEOMIC ANALYSIS; FETAL MEMBRANES; LUNG MATURITY; AMNIOCENTESIS
SPECIMENS
AB Aim: To describe a new device for the transcervical collection of amniotic fluid (AF) in patients with ruptured membranes, and to compare the concentration of proteins in fluid retrieved by transabdominal amniocentesis and the transcervical AF collector.
Study design: Paired AF samples were collected in patients with preterm prelabor rupture of membranes (PROM) (n = 11) by transabdominal amniocentesis and with the transcervical AF collector (Yoon's AF Collector T). Three proteins known to have high concentrations in AF [alpha-fetoprotein (AFP), beta-human chorionic gonadotrophin (beta-hCG), and prolactin] were measured.
Results: (1) There was a significant correlation between the concentrations of analytes in AF obtained by transabdominal amniocentesis and by the transcervical AF collector (r = 0.94, P < 0.001 for AFP; r = 0.96, P < 0.001 for beta-hCG; r = 0.72, P < 0.05 for prolactin); (2) Bland-Altman plots showed no evidence of heteroscedasticity between transabdominal or transcervical AF concentrations of these markers.
Conclusions: There was a strong correlation between the concentrations of proteins in AF collected by amniocentesis or with the transcervical device.
C1 [Romero, Roberto] Wayne State Univ, Hutzel Womens Hosp, NICHD NIH DHHS, Perinatol Res Branch, Detroit, MI 48201 USA.
[Lee, Seung Mi; Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South Korea.
[Lee, Seung Mi] Seoul Metropolitan Govt Seoul Natl Univ Boramae M, Dept Obstet & Gynecol, Seoul, South Korea.
[Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,NIH, Bethesda, MD USA.
[Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Div Intramural Res, Program Perinatal Res & Obstet,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.
[Park, Joong Shin; Jun, Jong Kwan] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul, South Korea.
[Chaemsaithong, Piya] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,NIH, Bethesda, MD USA.
[Chaemsaithong, Piya] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,NIH, Detroit, MI USA.
[Chaemsaithong, Piya] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, NICHD NIH DHHS, Perinatol Res Branch, 3990 John R,Box 4, Detroit, MI 48201 USA.
EM romeror@mail.nih.gov; yoonbh@snu.ac.kr
FU Division of Intramural Research of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development; NICHD
[HHSN275201300006C]; Korea Health Technology R&D Project through the
Korea Health Industry Development Institute (KHIDI); Ministry of Health
& Welfare, Republic of Korea [HI12C0768]
FX The participation of Roberto Romero in this research is funded by the
Division of Intramural Research of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, and, in part, by NICHD
Contract No. HHSN275201300006C and by a grant of the Korea Health
Technology R&D Project through the Korea Health Industry Development
Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic
of Korea (grant number: HI12C0768). All patients were recruited in South
Korea under IRB approved protocols, and assays were performed at the
Seoul National University Hospital, Seoul National University Bundang
Hospital or Dongguk University Hospital.
NR 105
TC 4
Z9 4
U1 0
U2 4
PU WALTER DE GRUYTER GMBH
PI BERLIN
PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY
SN 0300-5577
EI 1619-3997
J9 J PERINAT MED
JI J. Perinat. Med.
PD JUL
PY 2015
VL 43
IS 4
SI SI
BP 381
EP 389
DI 10.1515/jpm-2014-0276
PG 9
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA CN3JY
UT WOS:000358323400002
PM 25372723
ER
PT J
AU Lange-Maia, BS
Strotmeyer, ES
Harris, TB
Glynn, NW
Simonsick, EM
Brach, JS
Cauley, JA
Richey, PA
Schwartz, AV
Newman, AB
AF Lange-Maia, Brittney S.
Strotmeyer, Elsa S.
Harris, Tamara B.
Glynn, Nancy W.
Simonsick, Eleanor M.
Brach, Jennifer S.
Cauley, Jane A.
Richey, Phyllis A.
Schwartz, Ann V.
Newman, Anne B.
CA Hlth Aging Body Composition Study
TI Physical Activity and Change in Long Distance Corridor Walk Performance
in the Health, Aging, and Body Composition Study
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE aerobic fitness; physical activity; 400-m walk
ID FUNCTIONING OLDER-ADULTS; MAXIMAL AEROBIC CAPACITY; MOBILITY LIMITATION;
CARDIORESPIRATORY FITNESS; CARDIOVASCULAR-DISEASE; OXYGEN-UPTAKE;
FOLLOW-UP; AGE; EXERCISE; WOMEN
AB ObjectivesTo examine the prospective relationship between self-reported physical activity and aerobic fitness in the Health, Aging, and Body Composition Study (Health ABC) using the Long Distance Corridor Walk (LDCW).
DesignCohort study with 7years of follow-up.
SettingTwo U.S. clinical sites.
ParticipantsCommunity-dwelling older adults enrolled in Health ABC (N=3,075, aged 70-79, 52% female, 42% black) with no self-reported difficulty walking one-quarter of a mile or climbing 10 steps.
MeasurementsParticipants were classified based on a physical activity questionnaire as being inactive (1,000kcal/wk exercise activity, 2,719kcal/wk total physical activity), lifestyle active (1,000kcal/wk exercise activity, >2,719kcal/wk total physical activity), or exercisers (1,000kcal/wk exercise activity). The LDCW, an endurance walking test (400m), was administered at Years 1 (baseline), 2, 4, 6, and 8 to assess aerobic fitness.
ResultsAt baseline, LDCW completion times (adjusted for age and sex) were 351.8seconds (95% confidence interval (CI)=346.9-356.8seconds) for the inactive group, 335.9seconds (95% CI=332.7-339.1seconds) for the lifestyle active group, and 307.7seconds (95% CI=303.2-312.3seconds) for the exerciser group (P<.001). From baseline to Year 8, the inactive group slowed 36.1seconds (95% CI=28.4-43.8seconds), the lifestyle active group slowed 38.1seconds (95% CI=33.6-42.4seconds), and the exerciser group slowed 40.8seconds (95% CI=35.2-46.5seconds), and did not differ significantly between groups. In linear mixed-effects models, the rate of change in LDCW time did not differ between the groups, although exercisers consistently had the fastest completion times (P<.001 for all pairwise comparisons).
ConclusionDecline in LDCW time occurred regardless of baseline activity, although exercisers maintained higher aerobic fitness, which may delay reaching a critically low threshold of aerobic fitness at which independence is impaired.
C1 [Lange-Maia, Brittney S.; Strotmeyer, Elsa S.; Glynn, Nancy W.; Cauley, Jane A.; Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Ctr Aging & Populat Hlth, Pittsburgh, PA 15261 USA.
[Harris, Tamara B.] NIA, Intramural Res Program, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA.
[Simonsick, Eleanor M.] NIA, Intramural Res Program, Baltimore, MD 21224 USA.
[Brach, Jennifer S.] Univ Pittsburgh, Sch Hlth & Rehabil Sci, Dept Phys Therapy, Pittsburgh, PA 15261 USA.
[Richey, Phyllis A.] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN USA.
[Schwartz, Ann V.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
RP Newman, AB (reprint author), Univ Pittsburgh, Dept Epidemiol, 130 DeSoto St,A528 Crabtree Hall, Pittsburgh, PA 15261 USA.
EM newmana@edc.pitt.edu
RI Newman, Anne/C-6408-2013; Cauley, Jane/N-4836-2015;
OI Newman, Anne/0000-0002-0106-1150; Cauley, Jane/0000-0003-0752-4408;
Strotmeyer, Elsa/0000-0002-4093-6036; Glynn, Nancy/0000-0003-2265-0162
FU National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103,
N01-AG-6-2106, R01-AG028050]; National Institute of Nursing Research
[R01-NR012459]; National Institutes of Health, NIA; NIA [T32AG000181];
Patient-Centered Outcomes Research Institute [6301]
FX This research was supported by National Institute on Aging (NIA)
Contracts N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, and R01-AG028050
and National Institute of Nursing Research Grant R01-NR012459 and in
part by the Intramural Research Program of the National Institutes of
Health, NIA. BLM received funding from NIA Grant T32AG000181. JSB
received grant support from the Patient-Centered Outcomes Research
Institute (6301).
NR 41
TC 4
Z9 4
U1 3
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0002-8614
EI 1532-5415
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD JUL
PY 2015
VL 63
IS 7
BP 1348
EP 1354
DI 10.1111/jgs.13487
PG 7
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA CN2LZ
UT WOS:000358254200009
PM 26096803
ER
PT J
AU Chang, YC
Lamichhane, AK
Bradley, J
Rodgers, L
Ngamskulrungroj, P
Kwon-Chung, KJ
AF Chang, Yun C.
Lamichhane, Ami Khanal
Bradley, James
Rodgers, Laura
Ngamskulrungroj, Popchai
Kwon-Chung, Kyung J.
TI Differences between Cryptococcus neoformans and Cryptococcus gattii in
the Molecular Mechanisms Governing Utilization of D-Amino Acids as the
Sole Nitrogen Source
SO PLOS ONE
LA English
DT Article
ID D-PROLINE ASSIMILATION; D-ASPARTATE OXIDASE; PHYSIOLOGICAL-ROLE;
BRITISH-COLUMBIA; SEROTYPE-B; METABOLISM; YEAST; BACILLISPORUS;
OUTBREAK; CANADA
AB The ability to grow on media containing certain D-amino acids as a sole nitrogen source is widely utilized to differentiate Cryptococcus gattii from C. neoformans. We used the C. neoformans H99 and C. gattii R265 strains to dissect the mechanisms of D-amino acids utilization. We identified three putative D-amino acid oxidase (DAO) genes in both strains and showed that each DAO gene plays different roles in D-amino acid utilization in each strain. Deletion of DAO2 retarded growth of R265 on eleven D-amino acids suggesting its prominent role on D-amino acid assimilation in R265. All three R265 DAO genes contributed to growth on D-Asn and D-Asp. DAO3 was required for growth and detoxification of D-Glu by both R265 and H99. Although growth of H99 on most D-amino acids was poor, deletion of DAO1 or DAO3 further exacerbated it on four D-amino acids. Overexpression of DAO2 or DAO3 enabled H99 to grow robustly on several D-amino acids suggesting that expression levels of the native DAO genes in H99 were insufficient for growth on D-amino acids. Replacing the H99 DAO2 gene with a single copy of the R265 DAO2 gene also enabled its utilization of several D-amino acids. Results of gene and promoter swaps of the DAO2 genes suggested that enzymatic activity of Dao2 in H99 might be lower compared to the R265 strain. A reduction in virulence was only observed when all DAO genes were deleted in R265 but not in H99 indicating a pathobiologically exclusive role of the DAO genes in R265. These results suggest that C. neoformans and C. gattii divergently evolved in D-amino acid utilization influenced by their major ecological niches.
C1 [Chang, Yun C.; Lamichhane, Ami Khanal; Bradley, James; Rodgers, Laura; Kwon-Chung, Kyung J.] NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Ngamskulrungroj, Popchai] Mahidol Univ, Siriraj Hosp, Fac Med, Dept Microbiol, Bangkok 10700, Thailand.
RP Chang, YC (reprint author), NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM ychang@niaid.nih.gov
OI Bradley, James/0000-0001-5570-4679
FU National Institute of Allergy and Infectious Diseases, NIH
FX This study was supported by funds from the intramural program of the
National Institute of Allergy and Infectious Diseases, NIH. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 45
TC 1
Z9 1
U1 1
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 JUL 1
PY 2015
VL 10
IS 7
AR e0131865
DI 10.1371/journal.pone.0131865
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN1CG
UT WOS:000358153000142
PM 26132227
ER
PT J
AU Covell, DG
AF Covell, David G.
TI Data Mining Approaches for Genomic Biomarker Development: Applications
Using Drug Screening Data from the Cancer Genome Project and the Cancer
Cell Line Encyclopedia
SO PLOS ONE
LA English
DT Article
ID GROWTH-FACTOR RECEPTOR; BREAST-CANCER; TRANSCRIPTION FACTOR;
CONNECTIVITY MAP; SENSITIVITY; RESISTANCE; MUTATIONS; DISEASE; GENES;
IDENTIFICATION
AB Developing reliable biomarkers of tumor cell drug sensitivity and resistance can guide hypothesis-driven basic science research and influence pre-therapy clinical decisions. A popular strategy for developing biomarkers uses characterizations of human tumor samples against a range of cancer drug responses that correlate with genomic change; developed largely from the efforts of the Cancer Cell Line Encyclopedia (CCLE) and Sanger Cancer Genome Project (CGP). The purpose of this study is to provide an independent analysis of this data that aims to vet existing and add novel perspectives to biomarker discoveries and applications. Existing and alternative data mining and statistical methods will be used to a) evaluate drug responses of compounds with similar mechanism of action (MOA), b) examine measures of gene expression (GE), copy number (CN) and mutation status (MUT) biomarkers, combined with gene set enrichment analysis (GSEA), for hypothesizing biological processes important for drug response, c) conduct global comparisons of GE, CN and MUT as biomarkers across all drugs screened in the CGP dataset, and d) assess the positive predictive power of CGP-derived GE biomarkers as predictors of drug response in CCLE tumor cells. The perspectives derived from individual and global examinations of GEs, MUTs and CNs confirm existing and reveal unique and shared roles for these biomarkers in tumor cell drug sensitivity and resistance. Applications of CGP-derived genomic biomarkers to predict the drug response of CCLE tumor cells finds a highly significant ROC, with a positive predictive power of 0.78. The results of this study expand the available data mining and analysis methods for genomic biomarker development and provide additional support for using biomarkers to guide hypothesis-driven basic science research and pre-therapy clinical decisions.
C1 NCI, Screening Technol Branch, Dev Therapeut Program, Frederick, MD 21701 USA.
RP Covell, DG (reprint author), NCI, Screening Technol Branch, Dev Therapeut Program, Frederick, MD 21701 USA.
EM covelld@mail.nih.gov
NR 49
TC 1
Z9 1
U1 4
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 JUL 1
PY 2015
VL 10
IS 7
AR e0127433
DI 10.1371/journal.pone.0127433
PG 28
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN1CG
UT WOS:000358153000008
PM 26132924
ER
PT J
AU Karim, S
Ribeiro, JMC
AF Karim, Shahid
Ribeiro, Jose M. C.
TI An Insight into the Sialome of the Lone Star Tick, Amblyomma americanum,
with a Glimpse on Its Time Dependent Gene Expression
SO PLOS ONE
LA English
DT Article
ID TRANSCRIPTOME ANALYSIS; IXODES-SCAPULARIS; PROTEIN DATABASE;
SALIVARY-GLANDS; VECTOR; GENERATION; ASSEMBLER; IXODIDAE; PROGRAM; ABYSS
AB Hard ticks feed for several days or weeks on their hosts. Blood feeding is assisted by tick saliva, which is injected in the host skin regularly, alternating with blood ingestion. Tick saliva contains hundreds or thousands of different peptides and other bioactive compounds that assist feeding by inhibiting their hosts' blood clotting, platelet aggregation, vasoconstriction, as well as pain and itching. Immunomodulatory and antimicrobial peptides are also found in tick saliva. Molecular characterization of tick salivary compounds, or its sialome (from the Greek sialos = saliva), helps identification of possible antigens that might confer anti-tick immunity, as well as identifying novel pharmacologically active compounds. Amblyomma americanum is a major nuisance tick in Eastern and Southern US, being a vector of Theileria and Ehrlichia bacteria to animals and humans. Presently we report an RNA-seq study concerning the salivary glands of adult female A. americanum ticks, which involved sequencing of four libraries collected at different times of feeding. A total of 5,792 coding sequences were deduced from the transcriptome assembly, 3,139 of which were publicly deposited, expanding from the previously available 146 salivary sequences found in GenBank. A remarkable time-dependent transcript expression was found, mostly related to secretory products, supporting the idea that ticks may have several "sialomes" that are expressed at different times during feeding. The molecular nature of this sialome switching remains unknown.
C1 [Karim, Shahid] Univ So Mississippi, Dept Biol Sci, Hattiesburg, MS 39406 USA.
[Ribeiro, Jose M. C.] NIAID, Vector Biol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
RP Ribeiro, JMC (reprint author), NIAID, Vector Biol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
EM jribeiro@niaid.nih.gov
OI Ribeiro, Jose/0000-0002-9107-0818
FU Department of State award (PakistanUnited States Science and Technology
Cooperation) [PGA-P21049]; National Institutes of General Medical
Sciences award [P20RR016476]; Division of Intramural Research; National
Institute of Allergy and Infectious Diseases; National Institutes of
Health, USA; National Institute of Allergy and Infectious Diseases
award, United States [AI099919]
FX Department of State award #PGA-P21049 (PakistanUnited States Science and
Technology Cooperation) to SK and the National Institutes of General
Medical Sciences award # P20RR016476 to the MS-INBRE core facility. JMCR
was supported by the Division of Intramural Research, National Institute
of Allergy and Infectious Diseases, National Institutes of Health, USA.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.This work was
supported by grants from the National Institute of Allergy and
Infectious Diseases award # AI099919, United States
NR 33
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 JUL 1
PY 2015
VL 10
IS 7
AR e0131292
DI 10.1371/journal.pone.0131292
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CN1CG
UT WOS:000358153000109
PM 26131772
ER
PT J
AU Franco, EL
Shinder, GA
Tota, JE
Isidean, SD
AF Franco, Eduardo L.
Shinder, Gayle A.
Tota, Joseph E.
Isidean, Sandra D.
TI Sobering realizations in cancer prevention and screening and their
lessons
SO PREVENTIVE MEDICINE
LA English
DT Editorial Material
ID RISK
C1 [Franco, Eduardo L.; Tota, Joseph E.; Isidean, Sandra D.] McGill Univ, Dept Oncol, Montreal, PQ H2W 1S6, Canada.
[Franco, Eduardo L.; Isidean, Sandra D.] McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ H2W 1S6, Canada.
[Tota, Joseph E.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
RP Franco, EL (reprint author), McGill Univ, Div Canc Epidemiol, 546 Pine Ave West, Montreal, PQ H2W 1S6, Canada.
EM prev.med@mcgill.ca
OI Franco, Eduardo/0000-0002-4409-8084
FU Canadian Institutes of Health Research
NR 9
TC 1
Z9 1
U1 5
U2 7
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0091-7435
EI 1096-0260
J9 PREV MED
JI Prev. Med.
PD JUL
PY 2015
VL 76
BP 129
EP 131
DI 10.1016/j.ypmed.2015.04.014
PG 3
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA CN1OK
UT WOS:000358189100022
PM 25933986
ER
PT J
AU Deshields, T
Padgett, L
Lazenby, M
Zebrack, B
AF Deshields, Teresa
Padgett, Lynne
Lazenby, Mark
Zebrack, Brad
TI What can we learn from model programs for distress screening?
SO PSYCHO-ONCOLOGY
LA English
DT Meeting Abstract
C1 [Deshields, Teresa] Siteman Canc Ctr, St Peters, MO USA.
[Padgett, Lynne] NCI, Bethesda, MD 20892 USA.
[Lazenby, Mark] Council Middle East Studies, Nursing 2Sch, New Haven, CT USA.
[Lazenby, Mark] Council Middle East Studies, Divin & Core Fac, New Haven, CT USA.
[Zebrack, Brad] Univ Michigan, Sch Social Work, 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 1057-9249
EI 1099-1611
J9 PSYCHO-ONCOLOGY
JI Psycho-Oncol.
PD JUL
PY 2015
VL 24
SU 2
SI SI
MA S3-2
BP 5
EP 6
PG 2
WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences,
Biomedical
SC Oncology; Psychology; Biomedical Social Sciences
GA CN2MG
UT WOS:000358255000011
ER
PT J
AU Padgett, L
Zebrack, B
Lazenby, M
Deshields, T
AF Padgett, Lynne
Zebrack, Brad
Lazenby, Mark
Deshields, Teresa
TI What does an optimal model for distress screening look like? Developing
selection criteria to determine best practice
SO PSYCHO-ONCOLOGY
LA English
DT Meeting Abstract
C1 NCI, Bethesda, MD 20892 USA.
[Zebrack, Brad] Univ Michigan, Sch Social Work, Ann Arbor, MI 48109 USA.
[Lazenby, Mark] Council Middle East Studies, 2Sch Nursing, New Haven, CT USA.
[Lazenby, Mark] Council Middle East Studies, 2Sch Divin, New Haven, CT USA.
[Lazenby, Mark] Council Middle East Studies, Core Fac, New Haven, CT USA.
[Deshields, Teresa] Siteman Canc Ctr, St Peters, MO 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 1057-9249
EI 1099-1611
J9 PSYCHO-ONCOLOGY
JI Psycho-Oncol.
PD JUL
PY 2015
VL 24
SU 2
SI SI
MA S3-5
BP 6
EP 7
PG 2
WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences,
Biomedical
SC Oncology; Psychology; Biomedical Social Sciences
GA CN2MG
UT WOS:000358255000013
ER
PT J
AU Zadeh, S
Wiener, L
Battles, H
Pao, M
AF Zadeh, Sima
Wiener, Lori
Battles, Haven
Pao, Maryland
TI The development of a pediatric screen: next generation distress
thermometer?
SO PSYCHO-ONCOLOGY
LA English
DT Meeting Abstract
C1 [Zadeh, Sima; Wiener, Lori] NCI, NIH, Bethesda, MD 20892 USA.
[Battles, Haven] NCI, Bethesda, MD 20892 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 1057-9249
EI 1099-1611
J9 PSYCHO-ONCOLOGY
JI Psycho-Oncol.
PD JUL
PY 2015
VL 24
SU 2
SI SI
MA S7-4
BP 14
EP 15
PG 2
WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences,
Biomedical
SC Oncology; Psychology; Biomedical Social Sciences
GA CN2MG
UT WOS:000358255000028
ER
PT J
AU Rowland, J
AF Rowland, Julia
TI Securing funding for your research
SO PSYCHO-ONCOLOGY
LA English
DT Meeting Abstract
C1 [Rowland, Julia] 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 1057-9249
EI 1099-1611
J9 PSYCHO-ONCOLOGY
JI Psycho-Oncol.
PD JUL
PY 2015
VL 24
SU 2
SI SI
MA S9-3
BP 18
EP 18
PG 1
WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences,
Biomedical
SC Oncology; Psychology; Biomedical Social Sciences
GA CN2MG
UT WOS:000358255000035
ER
PT J
AU Zebrack, B
Kayser, K
Padgett, L
Jobin, C
Sundstrom, L
AF Zebrack, Brad
Kayser, Karen
Padgett, Lynne
Jobin, Chad
Sundstrom, Laura
TI Assessing institutional capacity to implement psychosocial support
services: the National Cancer Institute Psychosocial Care Matrix
SO PSYCHO-ONCOLOGY
LA English
DT Meeting Abstract
C1 [Zebrack, Brad] Univ Michigan, Sch Social Work, Ann Arbor, MI 48109 USA.
[Kayser, Karen] Univ Louisville, Kent Sch Social Work, Louisville, KY 40292 USA.
[Padgett, Lynne] NCI, Bethesda, MD 20892 USA.
[Jobin, Chad; Sundstrom, Laura] Univ Michigan, Curtis Ctr, Program Evaluat Grp, Ann Arbor, MI 48109 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 1057-9249
EI 1099-1611
J9 PSYCHO-ONCOLOGY
JI Psycho-Oncol.
PD JUL
PY 2015
VL 24
SU 2
SI SI
MA F-2
BP 53
EP 54
PG 2
WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences,
Biomedical
SC Oncology; Psychology; Biomedical Social Sciences
GA CN2MG
UT WOS:000358255000098
ER
PT J
AU Padgett, L
Rowland, J
AF Padgett, Lynne
Rowland, Julia
TI The Psychosocial Matrix: longitudinal study of use within the NCI
Community Cancer Centers Program (NCCCP)
SO PSYCHO-ONCOLOGY
LA English
DT Meeting Abstract
C1 [Padgett, Lynne; Rowland, Julia] 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 1057-9249
EI 1099-1611
J9 PSYCHO-ONCOLOGY
JI Psycho-Oncol.
PD JUL
PY 2015
VL 24
SU 2
SI SI
MA F-4
BP 54
EP 55
PG 2
WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences,
Biomedical
SC Oncology; Psychology; Biomedical Social Sciences
GA CN2MG
UT WOS:000358255000100
ER
PT J
AU Knight, J
Martens, M
Syrjala, K
Le-Rademacher, J
Brent, R
Lee, S
Jacobsen, P
Wood, W
Jim, H
Wingard, J
Horowitz, M
Majhail, N
Abidi, M
Geller, N
Fei, MW
Wu, J
Rizzo, JD
AF Knight, Jennifer
Martens, Michael
Syrjala, Karen
Le-Rademacher, Jennifer
Brent, R.
Lee, Stephanie
Jacobsen, Paul
Wood, William
Jim, Heather
Wingard, John
Horowitz, Mary
Majhail, Navneet
Abidi, Muneer
Geller, Nancy
Fei, Mingwei
Wu, Juan
Rizzo, J. Douglas
TI Pre-transplant health-related quality of life factors as predictors of
outcomes following hematopoietic cell transplantation: a study from the
BMT CTN 0902 trial
SO PSYCHO-ONCOLOGY
LA English
DT Meeting Abstract
C1 [Knight, Jennifer; Martens, Michael; Brent, R.; Horowitz, Mary] Med Coll Wisconsin, Madison, WI USA.
[Syrjala, Karen; Lee, Stephanie] Fred Hutchinson Canc Res Ctr, Seattle, WA USA.
[Le-Rademacher, Jennifer; Fei, Mingwei; Rizzo, J. Douglas] Ctr Int Blood & Marrow Transplant Res, Madison, WI USA.
[Jacobsen, Paul; Jim, Heather] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA.
[Wood, William] Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA.
[Wingard, John] Univ Florida, Coll Med, Gainesville, FL 32611 USA.
[Majhail, Navneet] Cleveland Clin, Cleveland, OH USA.
[Abidi, Muneer] Michigan State Univ, E Lansing, MI 48824 USA.
[Geller, Nancy] NHLBI, Bethesda, MD USA.
[Wu, Juan] EMMES Corp, Washington, DC 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 1057-9249
EI 1099-1611
J9 PSYCHO-ONCOLOGY
JI Psycho-Oncol.
PD JUL
PY 2015
VL 24
SU 2
SI SI
MA Z-3
BP 99
EP 99
PG 1
WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences,
Biomedical
SC Oncology; Psychology; Biomedical Social Sciences
GA CN2MG
UT WOS:000358255000176
ER
PT J
AU Bulotiene, G
Jagelaviciute, G
Urbutiene, E
AF Bulotiene, Giedre
Jagelaviciute, Gabriele
Urbutiene, Egle
TI Development and Evaluation of the Communication Skills Training Program
for Lithuanian Cancer Care Professionals
SO PSYCHO-ONCOLOGY
LA English
DT Meeting Abstract
C1 [Bulotiene, Giedre] NCI, Bethesda, MD 20892 USA.
[Jagelaviciute, Gabriele] Vilnius Univ, Vilnius, Lithuania.
[Urbutiene, Egle] Vilnius Univ, Hosp Santariskiu Klin, Vilnius, Lithuania.
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 1057-9249
EI 1099-1611
J9 PSYCHO-ONCOLOGY
JI Psycho-Oncol.
PD JUL
PY 2015
VL 24
SU 2
SI SI
MA P1-32
BP 120
EP 121
PG 2
WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences,
Biomedical
SC Oncology; Psychology; Biomedical Social Sciences
GA CN2MG
UT WOS:000358255000213
ER
PT J
AU Klagholz, S
Wehrlen, L
Ross, A
Stoops, E
Wiener, L
Zadeh, S
Yang, L
Bevans, M
AF Klagholz, Stephen
Wehrlen, Leslie
Ross, Alyson
Stoops, Elyssa
Wiener, Lori
Zadeh, Sima
Yang, Li
Bevans, Margaret
TI Are You Ready? Practical Considerations When Incorporating Web-based
Electronic Data Capture Systems of Patient-reported Outcomes in Clinical
Research
SO PSYCHO-ONCOLOGY
LA English
DT Meeting Abstract
C1 [Klagholz, Stephen; Wehrlen, Leslie; Ross, Alyson; Stoops, Elyssa; Yang, Li; Bevans, Margaret] NIH, Bethesda, MD USA.
[Wiener, Lori; Zadeh, Sima] NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1057-9249
EI 1099-1611
J9 PSYCHO-ONCOLOGY
JI Psycho-Oncol.
PD JUL
PY 2015
VL 24
SU 2
SI SI
MA P1-118
BP 166
EP 167
PG 2
WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences,
Biomedical
SC Oncology; Psychology; Biomedical Social Sciences
GA CN2MG
UT WOS:000358255000296
ER
PT J
AU de Arruda-Colli, MNF
Zadeh, S
Muriel, A
Pellentier, W
Wiener, L
AF de Arruda-Colli, Marina Noronha Ferraz
Zadeh, Sima
Muriel, Anna
Pellentier, Wendy
Wiener, Lori
TI In Good Times and in Bad: What Strengthens a Parental Relationship
during a Child's Cancer Trajectory?
SO PSYCHO-ONCOLOGY
LA English
DT Meeting Abstract
C1 [de Arruda-Colli, Marina Noronha Ferraz; Zadeh, Sima; Wiener, Lori] NCI, NIH, Bethesda, MD 20892 USA.
[Muriel, Anna] Dana Farber Canc Inst, Boston, MA USA.
[Pellentier, Wendy] Alberta Childrens Prov Gen Hosp, Calgary, AB, Canada.
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 1057-9249
EI 1099-1611
J9 PSYCHO-ONCOLOGY
JI Psycho-Oncol.
PD JUL
PY 2015
VL 24
SU 2
SI SI
MA P1-155
BP 185
EP 185
PG 1
WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences,
Biomedical
SC Oncology; Psychology; Biomedical Social Sciences
GA CN2MG
UT WOS:000358255000331
ER
PT J
AU Wiener, L
Viola, A
de Arruda-Colli, MNF
Zadeh, S
Glod, J
Widemann, B
AF Wiener, Lori
Viola, Adrienne
de Arruda-Colli, Marina Noronha Ferraz
Zadeh, Sima
Glod, John
Widemann, Brigitte
TI Psychosocial Correlates in Youth Living with Medullary Thyroid Carcinoma
(MTC)
SO PSYCHO-ONCOLOGY
LA English
DT Meeting Abstract
C1 [Wiener, Lori; de Arruda-Colli, Marina Noronha Ferraz; Zadeh, Sima; Glod, John; Widemann, Brigitte] NCI, NIH, Bethesda, MD 20892 USA.
[Viola, Adrienne] Rutgers Robert Wood Johnson Med Sch, New Brunswick, NJ 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 1057-9249
EI 1099-1611
J9 PSYCHO-ONCOLOGY
JI Psycho-Oncol.
PD JUL
PY 2015
VL 24
SU 2
SI SI
MA P1-192
BP 205
EP 205
PG 1
WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences,
Biomedical
SC Oncology; Psychology; Biomedical Social Sciences
GA CN2MG
UT WOS:000358255000368
ER
PT J
AU Chung, J
Radcliffe, J
Clayton, E
Snyder, D
Wiener, L
Horowitz, L
Zadeh, S
Nora, D
Pao, M
AF Chung, Joyce
Radcliffe, Jeanne
Clayton, Elizabeth
Snyder, Deborah
Wiener, Lori
Horowitz, Lisa
Zadeh, Sima
Nora, Diana
Pao, Maryland
TI A Pilot Study of the KSADS-PL To Assess the Mental Health of Adolescents
and Young Adults with and without Cancer
SO PSYCHO-ONCOLOGY
LA English
DT Meeting Abstract
C1 [Wiener, Lori; Zadeh, Sima] NCI, Bethesda, MD 20892 USA.
[Nora, Diana] Walter Reed Natl Mil Med Ctr, DVBIC, 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 1057-9249
EI 1099-1611
J9 PSYCHO-ONCOLOGY
JI Psycho-Oncol.
PD JUL
PY 2015
VL 24
SU 2
SI SI
MA P1-202
BP 210
EP 211
PG 2
WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences,
Biomedical
SC Oncology; Psychology; Biomedical Social Sciences
GA CN2MG
UT WOS:000358255000378
ER
PT J
AU Clayton, E
Wiener, L
Chung, J
AF Clayton, Elizabeth
Wiener, Lori
Chung, Joyce
TI Using the Course of Life Questionnaire to Examine Psychosocial
Development in Adolescent and Young Adult (AYA) Oncology Patients
SO PSYCHO-ONCOLOGY
LA English
DT Meeting Abstract
C1 [Wiener, Lori] 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 1057-9249
EI 1099-1611
J9 PSYCHO-ONCOLOGY
JI Psycho-Oncol.
PD JUL
PY 2015
VL 24
SU 2
SI SI
MA P1-208
BP 213
EP 214
PG 2
WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences,
Biomedical
SC Oncology; Psychology; Biomedical Social Sciences
GA CN2MG
UT WOS:000358255000384
ER
PT J
AU Powell, D
Zadeh, S
Pao, M
Wiener, L
AF Powell, Daniel
Zadeh, Sima
Pao, Maryland
Wiener, Lori
TI Perceived Level of Emotional Support and Self-reported Areas of
Post-traumatic Growth in Parents of Children Undergoing Cancer Treatment
SO PSYCHO-ONCOLOGY
LA English
DT Meeting Abstract
C1 [Zadeh, Sima; Wiener, Lori] NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 3
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1057-9249
EI 1099-1611
J9 PSYCHO-ONCOLOGY
JI Psycho-Oncol.
PD JUL
PY 2015
VL 24
SU 2
SI SI
MA P1-209
BP 214
EP 214
PG 1
WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences,
Biomedical
SC Oncology; Psychology; Biomedical Social Sciences
GA CN2MG
UT WOS:000358255000385
ER
PT J
AU de Arruda-Colli, MNF
Perina, EM
dos Santos, MA
AF Ferraz de Arruda-Colli, Marina Noronha
Perina, Elisa Maria
dos Santos, Manoel Antonio
TI When a Father Is the Primary Caregiver: The Experience during the
Childhood Cancer Relapse Treatment
SO PSYCHO-ONCOLOGY
LA English
DT Meeting Abstract
C1 [Ferraz de Arruda-Colli, Marina Noronha] NCI, NIH, Bethesda, MD 20892 USA.
[Perina, Elisa Maria] Univ Estadual Campinas, Campinas, SP, Brazil.
[dos Santos, Manoel Antonio] Univ Sao Paulo, BR-05508 Sao Paulo, Brazil.
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 1057-9249
EI 1099-1611
J9 PSYCHO-ONCOLOGY
JI Psycho-Oncol.
PD JUL
PY 2015
VL 24
SU 2
SI SI
MA P1-230
BP 224
EP 225
PG 2
WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences,
Biomedical
SC Oncology; Psychology; Biomedical Social Sciences
GA CN2MG
UT WOS:000358255000404
ER
PT J
AU Schepers, S
Haverman, L
Wiener, L
Grootenhuis, M
Zadeh, S
AF Schepers, Sasja
Haverman, Lotte
Wiener, Lori
Grootenhuis, Martha
Zadeh, Sima
TI Screening for Distress: What Patient-reported Information Do Pediatric
Oncology Providers Find Helpful?
SO PSYCHO-ONCOLOGY
LA English
DT Meeting Abstract
C1 [Schepers, Sasja; Haverman, Lotte; Grootenhuis, Martha] Emma Childrens Hosp AMC, Amsterdam, Netherlands.
[Wiener, Lori; Zadeh, Sima] NCI, NIH, 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 1057-9249
EI 1099-1611
J9 PSYCHO-ONCOLOGY
JI Psycho-Oncol.
PD JUL
PY 2015
VL 24
SU 2
SI SI
MA P2-16
BP 237
EP 238
PG 2
WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences,
Biomedical
SC Oncology; Psychology; Biomedical Social Sciences
GA CN2MG
UT WOS:000358255000428
ER
PT J
AU Davis, MH
Padgett, L
Frantz, V
Roberts, C
Stallings, H
Shelton, B
Shearer, A
AF Davis, Mary Helen
Padgett, Lynn
Frantz, Virginia
Roberts, Christy
Stallings, Holley
Shelton, Brent
Shearer, Andrew
TI Jumping over Hurdles: Palliative Care Pilot Project in Advanced Lung
Cancer
SO PSYCHO-ONCOLOGY
LA English
DT Meeting Abstract
C1 [Davis, Mary Helen; Roberts, Christy; Stallings, Holley] Norton Canc Inst, Louisville, KY USA.
[Padgett, Lynn] NCI, Bethesda, MD 20892 USA.
[Frantz, Virginia] Norton Healthcare, Louisville, KY USA.
[Shelton, Brent; Shearer, Andrew] Univ KY, Markey Canc Ctr, Louisville, KY 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 1057-9249
EI 1099-1611
J9 PSYCHO-ONCOLOGY
JI Psycho-Oncol.
PD JUL
PY 2015
VL 24
SU 2
SI SI
MA P2-27
BP 243
EP 243
PG 1
WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences,
Biomedical
SC Oncology; Psychology; Biomedical Social Sciences
GA CN2MG
UT WOS:000358255000439
ER
PT J
AU Loucas, C
Brand, S
Wiener, L
Zadeh, S
AF Loucas, Caitlyn
Brand, Sarah
Wiener, Lori
Zadeh, Sima
TI Preparing Youth with Cancer for Amputation: A Systematic Review
SO PSYCHO-ONCOLOGY
LA English
DT Meeting Abstract
C1 [Loucas, Caitlyn; Brand, Sarah] Dana Farber Canc Inst, Boston, MA USA.
[Wiener, Lori; Zadeh, Sima] NCI, NIH, 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 1057-9249
EI 1099-1611
J9 PSYCHO-ONCOLOGY
JI Psycho-Oncol.
PD JUL
PY 2015
VL 24
SU 2
SI SI
MA P2-60
BP 261
EP 261
PG 1
WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences,
Biomedical
SC Oncology; Psychology; Biomedical Social Sciences
GA CN2MG
UT WOS:000358255000472
ER
PT J
AU Prince, P
Wehrlen, L
Bevans, M
AF Prince, Patricia
Wehrlen, Leslie
Bevans, Margaret
TI 'Outside the Ring of Fire': Distress Screening for Cancer Caregivers
during Survivorship
SO PSYCHO-ONCOLOGY
LA English
DT Meeting Abstract
C1 [Prince, Patricia; Wehrlen, Leslie; Bevans, Margaret] NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1057-9249
EI 1099-1611
J9 PSYCHO-ONCOLOGY
JI Psycho-Oncol.
PD JUL
PY 2015
VL 24
SU 2
SI SI
MA P2-134
BP 299
EP 300
PG 2
WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences,
Biomedical
SC Oncology; Psychology; Biomedical Social Sciences
GA CN2MG
UT WOS:000358255000545
ER
PT J
AU Kumari, D
Swaroop, M
Southall, N
Huang, WW
Zheng, W
Usdin, K
AF Kumari, Daman
Swaroop, Manju
Southall, Noel
Huang, Wenwei
Zheng, Wei
Usdin, Karen
TI High-Throughput Screening to Identify Compounds That Increase Fragile X
Mental Retardation Protein Expression in Neural Stem Cells
Differentiated From Fragile X Syndrome Patient-Derived Induced
Pluripotent Stem Cells
SO STEM CELLS TRANSLATIONAL MEDICINE
LA English
DT Article
DE Fragile X syndrome; Fragile X mental retardation protein assay;
High-throughput screening; Fibroblasts; Induced pluripotent stem cells;
Neural stem cells
ID DNA-DAMAGE RESPONSE; CGG REPEAT; TREMOR/ATAXIA SYNDROME; MESSENGER-RNAS;
MOUSE MODEL; FMR1 GENE; TRANSLATION; PREMUTATION; NEURODEGENERATION;
IDENTIFICATION
AB Fragile X syndrome (FXS), the most common form of inherited cognitive disability, is caused by a deficiency of the fragile X mental retardation protein (FMRP). In most patients, the absence of FMRP is due to an aberrant transcriptional silencing of the fragile X mental retardation 1 (FMR1) gene. FXS has no cure, and the available treatments only provide symptomatic relief. Given that FMR1 gene silencing in FXS patient cells can be partially reversed by treatment with compounds that target repressive epigenetic marks, restoring FMRP expression could be one approach for the treatment of FXS. We describe a homogeneous and highly sensitive time-resolved fluorescence resonance energy transfer assay for FMRP detection in a 1,536-well plate format. Using neural stem cells differentiated from an FXS patient-derived induced pluripotent stem cell (iPSC) line that does not express any FMRP, we screened a collection of approximately 5,000 known tool compounds and approved drugs using this FMRP assay and identified 6 compounds that modestly increase FMR1 gene expression in FXS patient cells. Although none of these compounds resulted in clinically relevant levels of FMR1 mRNA, our data provide proof of principle that this assay combined with FXS patient-derived neural stem cells can be used in a high-throughput format to identify better lead compounds for FXS drug development.
C1 [Kumari, Daman; Usdin, Karen] NIDDK, Lab Cell & Mol Biol, NIH, Bethesda, MD 20892 USA.
[Swaroop, Manju; Southall, Noel; Huang, Wenwei; Zheng, Wei] NIH, Therapeut Rare & Neglected Dis, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA.
RP Kumari, D (reprint author), NIDDK, Lab Cell & Mol Biol, NIH, 8 Ctr Dr, Bethesda, MD 20892 USA.
EM damank@helix.nih.gov; wzheng@mail.nih.gov
RI Southall, Noel/H-8991-2012; Zheng, Wei/J-8889-2014
OI Southall, Noel/0000-0003-4500-880X; Zheng, Wei/0000-0003-1034-0757
FU Intramural Research Programs of the National Institute of Diabetes,
Digestive and Kidney Diseases; NIH Center for Regenerative Medicine;
National Center for Advancing Translational Sciences, NIH
FX We thank Dr. Carl Dobkin (Institute for Basic Research, New York, NY)
for analyzing the CGG-repeat size for the fibroblasts and SC128 iPSCs.
We thank Nicholas Sciascia (Usdin laboratory, NIH, Bethesda, MD) for
help with immunostaining of the SC128 neurons. We thank Paul Shinn from
the National Center for Advancing Translational Sciences (NIH,
Rockville, MD) for preparing compound plates. This study was funded by
the Intramural Research Programs of the National Institute of Diabetes,
Digestive and Kidney Diseases, the NIH Center for Regenerative Medicine,
and the National Center for Advancing Translational Sciences, NIH.
NR 42
TC 19
Z9 20
U1 2
U2 8
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 2157-6564
EI 2157-6580
J9 STEM CELL TRANSL MED
JI Stem Cells Transl. Med.
PD JUL
PY 2015
VL 4
IS 7
BP 800
EP 808
DI 10.5966/sctm.2014-0278
PG 9
WC Cell & Tissue Engineering
SC Cell Biology
GA CN2ST
UT WOS:000358272900019
PM 25999519
ER
PT J
AU Irvin, VL
Breen, N
Meissner, HI
Liu, BM
Kaplan, RM
AF Irvin, Veronica L.
Breen, Nancy
Meissner, Helen I.
Liu, Benmei
Kaplan, Robert M.
TI Non-normal Screening Mammography Results, Lumpectomies, and Breast
Cancer Reported by California Women, 2001-2009
SO WOMENS HEALTH ISSUES
LA English
DT Article
ID SERVICES TASK-FORCE; FAMILY-HISTORY; UNITED-STATES; SELF-REPORT;
POPULATION; RECALL; BIOPSY; BIAS; RECOMMENDATION; DISPARITIES
AB Background: Although screening mammography may contribute to decreases in breast cancer mortality in a population, it may also increase the risk of false positives, anxiety, and unnecessary and costly medical procedures in individuals. We report trends in self-reported non-normal screening mammography results, lumpectomies, and breast cancer in a representative sample of California women.
Methods: Data were obtained from the 2001, 2005, and 2009 cross-sectional California Health Interview Surveys (CHIS) and weighted to the California population. CHIS employed a multistage sampling design to administer telephone surveys in 6 languages. Our study sample was restricted to women 40 years and older who reported a screening mammogram in the past 2 years. Sample sizes were 13,974 in 2001, 12,069 in 2005, and 15,552 in 2009. Women reporting non-normal results were asked whether they had an operation to remove the lump and, if so, whether the lump was confirmed as malignant.
Findings: Between 2001 and 2009, the percent of California women who reported having been diagnosed with breast cancer was relatively stable. For each of the three age groups studied, the percentage of non-normal mammography results increased and the percentages of lumpectomies decreased and, for every woman reporting a diagnosis of breast cancer, three women reported a lumpectomy that turned out not to be cancer. This ratio was greater for younger women and less for older women.
Conclusions: Despite relatively constant rates of breast cancer diagnosis from 2001 to 2009, the percentage of non-normal mammography results increased and lumpectomies declined. Published by Elsevier Inc.
C1 [Irvin, Veronica L.] Oregon State Univ, Coll Publ Hlth Human Sci, Sch Social & Behav Hlth Sci, Hlth Promot & Hlth Behav, Corvallis, OR 97331 USA.
[Breen, Nancy] NCI, NIH, Hlth Syst & Intervent Res Branch, Healthcare Delivery Res Program, Rockville, MD USA.
[Meissner, Helen I.] NIH, Tobacco Regulatory Sci Program, Off Dis Prevent, Rockville, MD USA.
[Liu, Benmei] NCI, NIH, Div Canc Control & Populat Sci, Rockville, MD USA.
[Kaplan, Robert M.] Agcy Healthcare Res & Qual, Rockville, MD USA.
RP Irvin, VL (reprint author), Oregon State Univ, Coll Publ Hlth Human Sci, Sch Social & Behav Hlth Sci, 457 Waldo Hall, Corvallis, OR 97331 USA.
EM veronica.irvin@oregonstate.edu
OI Irvin, Veronica/0000-0001-6337-9108
FU Intramural Research Program of the Clinical Center, Department of
Rehabilitation Medicine; Division of Cancer Control and Population
Sciences at the National Cancer Institute; National Institutes of Health
FX This research was supported in part by the Intramural Research Program
of the Clinical Center, Department of Rehabilitation Medicine; and the
Division of Cancer Control and Population Sciences at the National
Cancer Institute, which are all part of the National Institutes of
Health. The funders had no role in the study design, data collection and
analysis, decision to publish, or preparation of the manuscript. The
views expressed in this article are those of the authors and do not
necessarily reflect the official policy or position of the National
Institutes of Health or the United States government.
NR 54
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 1049-3867
EI 1878-4321
J9 WOMEN HEALTH ISS
JI Womens Health Iss.
PD JUL-AUG
PY 2015
VL 25
IS 4
BP 331
EP 340
DI 10.1016/j.whi.2015.03.003
PG 10
WC Public, Environmental & Occupational Health; Women's Studies
SC Public, Environmental & Occupational Health; Women's Studies
GA CN7HK
UT WOS:000358604800004
PM 26070253
ER
PT J
AU Tosh, DK
Crane, S
Chen, ZM
Paoletta, S
Gao, ZG
Gizewski, E
Auchampach, JA
Salvemini, D
Jacobson, KA
AF Tosh, Dilip K.
Crane, Steven
Chen, Zhoumou
Paoletta, Silvia
Gao, Zhan-Guo
Gizewski, Elizabeth
Auchampach, John A.
Salvemini, Daniela
Jacobson, Kenneth A.
TI Rigidified A(3) Adenosine Receptor Agonists: 1-Deazaadenine Modification
Maintains High in Vivo Efficacy
SO ACS MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE G protein-coupled receptor; purines; chronic neuropathic pain; molecular
modeling; adenosine receptor; crystallographic structure
ID CARBOCYCLIC NUCLEOSIDES; PAIN; RAT; MITSUNOBU; ANALOGS; DESIGN
AB Substitution of rigidified A(3) adenosine receptor (AR) agonists with a 2-((5-chlorothiophen-2-y1)ethynyl) or a 2-(4-(5-chlorothiophen-2-y1)-1H-1,2,3-triazol-1-yl)) group provides prolonged protection in a model of chronic neuropathic pain. These agonists contain a bicyclo[3.1.0]hexane ((N)-methanocarba) ring system in place of ribose, which adopts a receptor-preferred conformation. N-6-Small alkyl derivatives were newly optimized for A(3)AR affinity and the effects of a 1-deaza-adenine modification probed. 1-Deaza-N-6-ethyl alkyne 20 (MRS7144, K-i 1.7 nM) and 1-aza N-6-propyl alkyne 12 (MRS7154, K-i 1.1 nM) were highly efficacious in vivo. Thus, the presence of N1 is not required for nanomolar binding affinity or potent, long-lasting functional activity. Docking of 1-deaza compounds to a receptor homology model confirmed a similar binding mode as previously reported 1-aza derivatives. This is the first demonstration in nonribose adenosine analogues that the 1-deaza modification can maintain high A(3)AR affinity, selectivity, and efficacy.
C1 [Tosh, Dilip K.; Crane, Steven; Paoletta, Silvia; Gao, Zhan-Guo; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Chen, Zhoumou; Salvemini, Daniela] St Louis Univ, Sch Med, Dept Pharmacol & Physiol Sci, St Louis, MO 63104 USA.
[Gizewski, Elizabeth; Auchampach, John A.] Med Coll Wisconsin, Dept Pharmacol, Milwaukee, WI 53226 USA.
RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
EM kennethj@helix.nih.gov
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
FU NIH Intramural Research Program (NIDDK); National Cancer Institute
[R01CA169519]; National Heart Lung Institute [R0IHL077707]
FX We thank the NIH Intramural Research Program (NIDDK); National Cancer
Institute (R01CA169519); and National Heart Lung Institute (R0IHL077707)
for support and John Lloyd and Noel Whittaker (NIDDK) for mass spectral
determinations.
NR 20
TC 4
Z9 4
U1 0
U2 4
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1948-5875
J9 ACS MED CHEM LETT
JI ACS Med. Chem. Lett.
PD JUL
PY 2015
VL 6
IS 7
BP 804
EP 808
DI 10.1021/acsmedchemlett.5b00150
PG 5
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA CM8QE
UT WOS:000357965900014
PM 26191370
ER
PT J
AU Malinska, M
Dauter, M
Kowiel, M
Jaskolski, M
Dauter, Z
AF Malinska, Maura
Dauter, Miroslawa
Kowiel, Marcin
Jaskolski, Mariusz
Dauter, Zbigniew
TI Protonation and geometry of histidine rings
SO ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
LA English
DT Article
DE imidazole; histidine protonation; hydrogen bond; X-ray crystal
structure; stereochemical restraints
ID CAMBRIDGE STRUCTURAL DATABASE; CRYSTAL-STRUCTURES; STRUCTURE REFINEMENT;
PROTEINS; RESOLUTION; RESTRAINTS; PARAMETERS; ACCURATE; STATE; BOND
AB The presence of H atoms connected to either or both of the two N atoms of the imidazole moiety in a histidine residue affects the geometry of the five-membered ring. Analysis of the imidazole moieties found in histidine residues of atomic resolution protein crystal structures in the Protein Data Bank (PDB), and in small-molecule structures retrieved from the Cambridge Structural Database (CSD), identified characteristic patterns of bond lengths and angles related to the protonation state of the imidazole moiety. Using discriminant analysis, two functions could be defined, corresponding to linear combinations of the four most sensitive stereochemical parameters, two bond lengths (ND1-CE1 and CE1-NE2) and two endocyclic angles (-ND1- and -NE2-), that uniquely identify the protonation states of all imidazole moieties in the CSD and can be used to predict which N atom(s) of the histidine side chains in protein structures are protonated. Updated geometrical restraint target values are proposed for differently protonated histidine side chains for use in macromolecular refinement.
C1 [Malinska, Maura; Dauter, Zbigniew] NCI, Synchrotron Radiat Res Sect, MCL, Argonne Natl Lab, Argonne, IL 60439 USA.
[Dauter, Miroslawa] Leidos Biomedical Res Inc, Basic Sci Program, Argonne Natl Lab, Argonne, IL 60439 USA.
[Kowiel, Marcin] Poznan Univ Med Sci, Dept Organ Chem, Poznan, Poland.
[Jaskolski, Mariusz] Adam Mickiewicz Univ, Fac Chem, Dept Crystallog, PL-60780 Poznan, Poland.
[Jaskolski, Mariusz] Polish Acad Sci, Inst Bioorgan Chem, Ctr Biocrystallog Res, Poznan, Poland.
RP Dauter, Z (reprint author), NCI, Synchrotron Radiat Res Sect, MCL, Argonne Natl Lab, Argonne, IL 60439 USA.
EM dauter@anl.gov
OI Malinska, Maura/0000-0002-7138-7041
FU Intramural Research Program of the National Cancer Institute, Center for
Cancer Research; Federal funds from the National Cancer Institute,
National Institutes of Health [HHSN261200800E]; National Science Center
[2013/10/M/NZ1/00251]; Polish Ministry of Science and Higher Education
through the 'Mobility Plus' program
FX This project was supported in part by the Intramural Research Program of
the National Cancer Institute, Center for Cancer Research and with
Federal funds from the National Cancer Institute, National Institutes of
Health (Contract No. HHSN261200800E). The content of this publication
does not necessarily reflect the views or policies of the US Department
of Health and Human Services, nor does mention of trade names,
commercial products, or organizations imply endorsement by the US
Government. The collaboration of MJ and ZD was supported in part by a
grant (2013/10/M/NZ1/00251) from the National Science Center. MM
acknowledges the Polish Ministry of Science and Higher Education for
financial support through the 'Mobility Plus' program.
NR 31
TC 2
Z9 2
U1 2
U2 19
PU INT UNION CRYSTALLOGRAPHY
PI CHESTER
PA 2 ABBEY SQ, CHESTER, CH1 2HU, ENGLAND
SN 2059-7983
J9 ACTA CRYSTALLOGR D
JI Acta Crystallogr. Sect. D-Struct. Biol.
PD JUL
PY 2015
VL 71
BP 1444
EP 1454
DI 10.1107/S1399004715007816
PN 7
PG 11
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Biophysics; Crystallography
SC Biochemistry & Molecular Biology; Biophysics; Crystallography
GA CM6VQ
UT WOS:000357829500004
PM 26143916
ER
PT J
AU Fadel, F
Zhao, YG
Cachau, R
Cousido-Siah, A
Ruiz, FX
Harlos, K
Howard, E
Mitschler, A
Podjarny, A
AF Fadel, Firas
Zhao, Yuguang
Cachau, Raul
Cousido-Siah, Alexandra
Ruiz, Francesc X.
Harlos, Karl
Howard, Eduardo
Mitschler, Andre
Podjarny, Alberto
TI New insights into the enzymatic mechanism of human chitotriosidase
(CHIT1) catalytic domain by atomic resolution X-ray diffraction and
hybrid QM/MM
SO ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
LA English
DT Article
DE CHIT1; GH18 chitinase; crystal structures; protonation states;
hydrolysis; catalytic mechanism
ID FAMILY 18 CHITINASES; SUBSTRATE-ASSISTED CATALYSIS; VIBRIO-HARVEYI
CHITINASE; BARRIER HYDROGEN-BOND; CRYSTAL-STRUCTURE; GLYCOSYL
HYDROLASES; MAMMALIAN CHITINASE; SERRATIA-MARCESCENS; ACTIVE-SITE;
CRYSTALLOGRAPHIC REFINEMENT
AB Chitotriosidase (CHIT1) is a human chitinase belonging to the highly conserved glycosyl hydrolase family 18 (GH18). GH18 enzymes hydrolyze chitin, an N-acetylglucosamine polymer synthesized by lower organisms for structural purposes. Recently, CHIT1 has attracted attention owing to its upregulation in immune-system disorders and as a marker of Gaucher disease. The 39 kDa catalytic domain shows a conserved cluster of three acidic residues, Glu140, Asp138 and Asp136, involved in the hydrolysis reaction. Under an excess concentration of substrate, CHIT1 and other homologues perform an additional activity, transglycosylation. To understand the catalytic mechanism of GH18 chitinases and the dual enzymatic activity, the structure and mechanism of CHIT1 were analyzed in detail. The resolution of the crystals of the catalytic domain was improved from 1.65 angstrom (PDB entry 1waw) to 0.95-1.10 angstrom for the apo and pseudo-apo forms and the complex with chitobiose, allowing the determination of the protonation states within the active site. This information was extended by hybrid quantum mechanics/molecular mechanics (QM/MM) calculations. The results suggest a new mechanism involving changes in the conformation and protonation state of the catalytic triad, as well as a new role for Tyr27, providing new insights into the hydrolysis and transglycosylation activities.
C1 [Fadel, Firas; Cousido-Siah, Alexandra; Ruiz, Francesc X.; Howard, Eduardo; Mitschler, Andre; Podjarny, Alberto] CNRS INSERM UdS, Dept Integrat Struct Biol, Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch Graffenstaden, France.
[Zhao, Yuguang; Harlos, Karl] Univ Oxford, Div Struct Biol, Wellcome Trust Ctr Human Genet, Oxford, England.
[Cachau, Raul] Leidos Biomed Res Inc, Adv Biomed Comp Ctr, Informat Syst Program, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Howard, Eduardo] UNLP, CONICET, IFLYSIB, La Plata, Buenos Aires, Argentina.
RP Fadel, F (reprint author), UMR7255 CNRS, LISM, 31 Chemin Joseph Aiguier, F-13402 Marseille 20, France.
EM firasfadel1@gmail.com; podjarny@igbmc.fr
OI Podjarny, Alberto/0000-0002-7685-1077
FU CNRS; INSERM; Strasbourg University; Biostruct-X (FP7) [283570];
Instruct (European Strategy Forum of Research Infrastructures; ESFRI);
French Infrastructure for Integrated Structural Biology (FRISBI)
FX We thank the IGBMC Structural Biology and Genomics Platform staff for
technical assistance. We are grateful to Dr Irene Yujnovsky and Dr
Sergey Melnikov for helpful discussions. The crystallographic
experiments were performed on the X06DA (PXIII) beamline at the Swiss
Light Source synchrotron, Paul Scherrer Institut, Villigen, Switzerland.
We thank, in particular, Ezequiel Panepucci and Vincent Olieric for
their help with data collection. This work has been funded by the CNRS,
the INSERM, Strasbourg University, Biostruct-X (FP7, contract 283570),
Instruct (European Strategy Forum of Research Infrastructures; ESFRI)
and the French Infrastructure for Integrated Structural Biology
(FRISBI).
NR 66
TC 2
Z9 2
U1 3
U2 14
PU INT UNION CRYSTALLOGRAPHY
PI CHESTER
PA 2 ABBEY SQ, CHESTER, CH1 2HU, ENGLAND
SN 2059-7983
J9 ACTA CRYSTALLOGR D
JI Acta Crystallogr. Sect. D-Struct. Biol.
PD JUL
PY 2015
VL 71
BP 1455
EP 1470
DI 10.1107/S139900471500783X
PN 7
PG 16
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Biophysics; Crystallography
SC Biochemistry & Molecular Biology; Biophysics; Crystallography
GA CM6VQ
UT WOS:000357829500005
PM 26143917
ER
PT J
AU Torrelo, A
Colmenero, I
Requena, L
Paller, AS
Ramot, Y
Lee, CCR
Vera, A
Zlotogorski, A
Goldbach-Mansky, R
Kutzner, H
AF Torrelo, Antonio
Colmenero, Isabel
Requena, Luis
Paller, Amy S.
Ramot, Yuval
Lee, Chyi-Chia Richard
Vera, Angel
Zlotogorski, Abraham
Goldbach-Mansky, Raphaela
Kutzner, Heinz
TI Histologic and Immunohistochemical Features of the Skin Lesions in
CANDLE Syndrome
SO AMERICAN JOURNAL OF DERMATOPATHOLOGY
LA English
DT Article
ID ATYPICAL NEUTROPHILIC DERMATOSIS; LIPODYSTROPHY; INTERFERON; SURVIVAL;
FACES
AB Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome is a newly characterized autoinflammatory disorder, caused by mutations in PSMB8. It is characterized by early-onset fevers, accompanied by a widespread, violaceous, and often annular cutaneous eruption. Although the exact pathogenesis of this syndrome is still obscure, it is postulated that the inflammatory disease manifestations stem from excess secretion of interferons. Based on preliminary blood cytokine and gene expression studies, the signature seems to come mostly from type I interferons, which are proposed to lead to the recruitment of immature myeloid cells into the dermis and subcutis. In this study, we systematically analyzed skin biopsies from 6 patients with CANDLE syndrome by routine histopathology and immunohistochemistry methods. Skin lesions showed the presence of extensive mixed dermal and subcutaneous inflammatory infiltrate, composed of mononuclear cells, atypical myeloid cells, neutrophils, eosinophils, and some mature lymphocytes. Positive LEDER and myeloperoxidase staining supported the presence of myeloid cells. Positive CD68/PMG1 and CD163 staining confirmed the existence of histiocytes and monocytic macrophages in the inflammatory infiltrate. CD123 staining was positive, demonstrating the presence of plasmacytoid dendritic cells. Uncovering the unique histopathological and immunohistochemical features of CANDLE syndrome provides tools for rapid and specific diagnosis of this disorder and further insight into the pathogenesis of this severe life-threatening condition.
C1 [Torrelo, Antonio] Hosp Nino Jesus, Dept Dermatol, Madrid 28009, Spain.
[Colmenero, Isabel] Birmingham Childrens Hosp, Paediat Histopathol Dept, Birmingham, W Midlands, England.
[Requena, Luis] Fdn Jimenez Diaz, Dept Dermatol, E-28040 Madrid, Spain.
[Paller, Amy S.] Northwestern Univ, Dept Dermatol, Chicago, IL 60611 USA.
[Ramot, Yuval; Zlotogorski, Abraham] Hadassah Hebrew Univ, Med Ctr, Dept Dermatol, Jerusalem, Israel.
[Ramot, Yuval; Zlotogorski, Abraham] Hadassah Hebrew Univ, Med Ctr, Ctr Genet Dis Skin & Hair, Jerusalem, Israel.
[Lee, Chyi-Chia Richard] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Vera, Angel] Hosp Carlos Haya, Dept Dermatol, Malaga, Spain.
[Goldbach-Mansky, Raphaela] NIAMS, Translat Autoinflammatory Dis Sect, NIH, Bethesda, MD USA.
[Kutzner, Heinz] Dermatohistopathol Gemeinschaftslab, Friedrichshafen, Germany.
RP Torrelo, A (reprint author), Hosp Nino Jesus, Dept Dermatol, Menendez Pelayo 65, Madrid 28009, Spain.
EM atorrelo@aedv.es
FU NIAMS Intramural Research Program (IRP) at the National Institutes of
Health (NIH); Authority for Research and Development, Hebrew University
of Jerusalem; Young clinician's grant, Hadassah-Hebrew University
Medical Center
FX Supported in part by the NIAMS Intramural Research Program (IRP) at the
National Institutes of Health (NIH) (R.G.-M.); The Authority for
Research and Development, Hebrew University of Jerusalem (A.Z.); and the
Young clinician's grant, Hadassah-Hebrew University Medical Center
(Y.R.). The remaining authors declare no conflicts of interest.
NR 17
TC 5
Z9 6
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0193-1091
EI 1533-0311
J9 AM J DERMATOPATH
JI Am. J. Dermatopathol.
PD JUL
PY 2015
VL 37
IS 7
BP 517
EP 522
DI 10.1097/DAD.0000000000000340
PG 6
WC Dermatology
SC Dermatology
GA CM5JE
UT WOS:000357723300002
PM 26091509
ER
PT J
AU Hsieh, YH
Kelen, GD
Laeyendecker, O
Kraus, CK
Quinn, TC
Rothman, RE
AF Hsieh, Yu-Hsiang
Kelen, Gabor D.
Laeyendecker, Oliver
Kraus, Chadd K.
Quinn, Thomas C.
Rothman, Richard E.
TI HIV Care Continuum for HIV-Infected Emergency Department Patients in an
Inner-City Academic Emergency Department
SO ANNALS OF EMERGENCY MEDICINE
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; UNITED-STATES; ANTIRETROVIRAL TREATMENT;
ED PATIENTS; PREVENTION; POPULATION; RECOMMENDATIONS; TRANSMISSION;
ENGAGEMENT; INTERVENTION
AB Study objective: The recently released HIV Care Continuum Initiative is a cornerstone of the National AIDS Strategy and a model for improving care for those living with HIV. To our knowledge, there are no studies exploring the entirety of the HIV Care Continuum for patients in the emergency department (ED). We determine gaps in the HIV Care Continuum to identify potential opportunities for improved care for HIV-infected ED patients.
Methods: A mixed-methods approach was used in 1 inner-city ED in 2007. Data elements were derived from an identityunlinked HIV seroprevalence study, an ongoing nontargeted HIV screening program, and a structured survey of known HIV-positive ED patients.
Results: Identity-unlinked testing of 3,417 unique ED patients found that 265 (7.8%) were HIV positive. Of patients testing HIV positive, 73% had received a previous diagnosis (based on self-report, chart review, or presence of antiretrovirals in serum), but only 61% were recognized by the clinician as being HIV infected (based on self-report or chart review). Of patients testing positive, 43% were linked to care, 39% were retained in care, 27% were receiving antiretrovirals, 26% were aware of their receiving antiretroviral treatment, 22% were virally suppressed, and only 9% were self-aware of their viral suppression.
Conclusion: To our knowledge, this study is the first to quantify gaps in HIV care for an ED patient population, with the HIV Care Continuum as a framework. Our findings identified distinct phases (ie, testing, provider awareness of HIV diagnosis, and linkage to care) in which the greatest opportunities for intervention exist, if appropriate resources were allocated. This schema could serve as a model for other indolent treatable diseases frequently observed in EDs, where continuity of care is critical.
C1 [Hsieh, Yu-Hsiang; Kelen, Gabor D.; Rothman, Richard E.] Johns Hopkins Univ, Sch Med, Dept Emergency Med, Baltimore, MD 21218 USA.
[Laeyendecker, Oliver; Quinn, Thomas C.; Rothman, Richard E.] Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21205 USA.
[Laeyendecker, Oliver; Quinn, Thomas C.] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Kraus, Chadd K.] Lehigh Valley Hlth Network, Allentown, PA USA.
RP Hsieh, YH (reprint author), Johns Hopkins Univ, Sch Med, Dept Emergency Med, Baltimore, MD 21218 USA.
EM yhsieh1@jhmi.edu
OI Rothman, Richard/0000-0002-1017-9505; Kelen, Gabor/0000-0002-3236-8286;
Laeyendecker, Oliver/0000-0002-6429-4760
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health (NIH); Maryland
Department of Health and Mental Hygiene; NIH from National Institute of
Allergy and Infectious Diseases [5K01AI100681]
FX By Annals policy, all authors are required to disclose any and all
commercial, financial, and other relationships in any way related to the
subject of this article as per ICMJE conflict of interest guidelines
(see www.icmje.org). The authors have stated that no such relationships
exist and provided the following details: The study was supported by the
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health (NIH). The Johns
Hopkins University Department of Emergency Medicine HIV Testing Program
was funded in part by grants from the Maryland Department of Health and
Mental Hygiene. Dr. Hsieh is also supported in part by an NIH award,
5K01AI100681, from National Institute of Allergy and Infectious Diseases
to study HIV testing in EDs with a modeling approach.
NR 51
TC 10
Z9 10
U1 1
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0196-0644
J9 ANN EMERG MED
JI Ann. Emerg. Med.
PD JUL
PY 2015
VL 66
IS 1
BP 69
EP 78
DI 10.1016/j.annemergmed.2015.01.001
PG 10
WC Emergency Medicine
SC Emergency Medicine
GA CM3AU
UT WOS:000357554400017
PM 25720801
ER
PT J
AU Liu-Chittenden, Y
Jain, M
Kumar, P
Patel, D
Aufforth, R
Neychev, V
Sadowski, S
Gara, SK
Joshi, BH
Cottle-Delisle, C
Merkel, R
Yang, L
Miettinen, M
Puri, RK
Kebebew, E
AF Liu-Chittenden, Yi
Jain, Meenu
Kumar, Parag
Patel, Dhaval
Aufforth, Rachel
Neychev, Vladimir
Sadowski, Samira
Gara, Sudheer K.
Joshi, Bharat H.
Cottle-Delisle, Candice
Merkel, Roxanne
Yang, Lily
Miettinen, Markku
Puri, Raj K.
Kebebew, Electron
TI Phase I trial of systemic intravenous infusion of
interleukin-13-Pseudomonas exotoxin in patients with metastatic
adrenocortical carcinoma
SO CANCER MEDICINE
LA English
DT Article
DE IL-13-PE; maximum-tolerated dose; metastatic adrenocortical carcinoma;
pharmacokinetics; Phase I; systemic administration
ID CONVECTION-ENHANCED DELIVERY; CHIMERIC FUSION PROTEINS; RECEPTOR ALPHA-2
CHAIN; PSEUDOMONAS EXOTOXIN; MALIGNANT GLIOMAS; CELL CARCINOMA; CANCER
THERAPY; EXPRESSION; TARGET; IL-13
AB Adrenocortical carcinoma (ACC) is a rare but lethal malignancy without effective current therapy for metastatic disease. IL-13-PE is a recombinant cytotoxin consisting of human interleukin-13 (IL-13) and a truncated form of Pseudomonas exotoxin A (PE). The main objectives of this Phase I dose-escalation trial were to assess the maximum-tolerated dose (MTD), safety, and pharmacokinetics (PK) of IL-13-PE in patients with metastatic ACC. Eligible patients had confirmed IL-13 receptor alpha 2 (IL-13R2) expressions in their tumors. IL-13-PE at dose of 1-2g/kg was administered intravenously (IV) on day 1, 3, and 5 in a 4-week cycle. Six patients received 1g/kg and two patients received 2g/kg of IL-13-PE. Dose-limiting toxicity was observed at 2g/kg, at which patients exhibited thrombocytopenia and renal insufficiency without requiring dialysis. PK analysis demonstrated that at MTD, the mean maximum serum concentration (C-max) of IL-13-PE was 21.0ng/mL, and the terminal half-life of IL-13-PE was 30-39min. Two (25%) of the eight patients had baseline neutralizing antibodies against PE. Three (75%) of the remaining four tested patients developed neutralizing antibodies against IL-13-PE within 14-28days of initial treatment. Of the five patients treated at MTD and assessed for response, one patient had stable disease for 5.5months before disease progression; the others progressed within 1-2months. In conclusion, systemic IV administration of IL-13-PE is safe at 1g/kg. All tested patients developed high levels of neutralizing antibodies during IL-13-PE treatment. Use of strategies for immunodepletion before IL-13-PE treatment should be considered in future trials.
C1 [Liu-Chittenden, Yi; Jain, Meenu; Patel, Dhaval; Aufforth, Rachel; Neychev, Vladimir; Sadowski, Samira; Gara, Sudheer K.; Cottle-Delisle, Candice; Merkel, Roxanne; Yang, Lily; Kebebew, Electron] NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Kumar, Parag] NIH, Clin Pharmacokinet Res Lab, Ctr Clin, Dept Pharm, Bethesda, MD 20892 USA.
[Joshi, Bharat H.; Puri, Raj K.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Silver Spring, MD USA.
[Miettinen, Markku] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
RP Kebebew, E (reprint author), NCI, Endocrine Oncol Branch, NIH, 10 Ctr Dr,Room 4-5952, Bethesda, MD 20892 USA.
EM kebebewe@mail.nih.gov
RI Gara, Sudheer Kumar/E-8084-2016;
OI Liu-Chittenden, Yi/0000-0001-6357-5360; Patel,
Dhaval/0000-0002-5744-568X
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health [1 ZIA BC011286 05]
FX This research was supported by the intramural research program of the
Center for Cancer Research, National Cancer Institute, National
Institutes of Health (grant # 1 ZIA BC011286 05).
NR 27
TC 4
Z9 5
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2045-7634
J9 CANCER MED-US
JI Cancer Med.
PD JUL
PY 2015
VL 4
IS 7
BP 1060
EP 1068
DI 10.1002/cam4.449
PG 9
WC Oncology
SC Oncology
GA CM7TJ
UT WOS:000357899100011
PM 25767039
ER
PT J
AU McMaster, ML
Heimdal, KR
Loud, JT
Bracci, JS
Rosenberg, PS
Greene, MH
AF McMaster, Mary L.
Heimdal, Ketil R.
Loud, Jennifer T.
Bracci, Janet S.
Rosenberg, Philip S.
Greene, Mark H.
TI Nontesticular cancers in relatives of testicular germ cell tumor (TGCT)
patients from multiple-case TGCT families
SO CANCER MEDICINE
LA English
DT Article
DE Familial cancer syndromes; genetic susceptibility; testicular germ cell
tumors
ID 1ST-DEGREE RELATIVES; RISK-FACTORS; SUSCEPTIBILITY; MEN; DENMARK;
BREAST; DMRT1; GENE; PREDISPOSITION; PHENOTYPE
AB Testicular germ cell tumors (TGCT) exhibit striking familial aggregation that remains incompletely explained. To improve the phenotypic definition of familial TGCT (FTGCT), we studied an international cohort of multiple-case TGCT families to determine whether first-degree relatives of FTGCT cases are at increased risk of other types of cancer. We identified 1041 first-degree relatives of TGCT cases in 66 multiple-case TGCT families from Norway and 64 from the United States (combined follow-up of 31,556person-years). We collected data on all cancers (except nonmelanoma skin cancers) reported by the family informant in these relatives, and we attempted to verify all reported cancer diagnoses through medical or cancer registry records. We calculated observed-to-expected (O/E) standardized incidence ratios, together with 95% confidence intervals (CI), for invasive cancers other than TGCT. We found no increase in risk of cancer overall (Norway O/E=0.8; 95% CI: 0.6-1.1 and United States O/E=0.9; 95% CI: 0.7-1.3). Site-specific analyses pooled across the two countries revealed a leukemia excess (O/E=6.5; 95% CI: 3.0-12.3), deficit of female breast cancer (O/E=0.0; 95% CI: 0.0-0.6) and increased risk of soft tissue sarcoma (O/E=7.2; 95% CI: 2.0-18.4); in all instances, these results were based on small case numbers and statistically significant only in Norway. While limited by sample size and potential issues relating to completeness of cancer reporting, this study in multiple-case TGCT families does not support the hypothesis that cancers other than testis cancer contribute to the FTGCT phenotype.
C1 [McMaster, Mary L.; Loud, Jennifer T.; Rosenberg, Philip S.; Greene, Mark H.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[McMaster, Mary L.] US Dept HHS, Commissioned Corps US Publ Hlth Serv, Washington, DC 20201 USA.
[Heimdal, Ketil R.] Univ Oslo, Rikshosp, Oslo Univ Hosp, Sect Clin Genet,Dept Med Genet, N-0027 Oslo, Norway.
[Bracci, Janet S.] WESTAT Corp, Rockville, MD 20850 USA.
RP Greene, MH (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 6E-456, Rockville, MD 20850 USA.
EM greenem@mail.nih.gov
OI Heimdal, Ketil/0000-0002-8911-3508
FU National Cancer Institute (NCI) [02-C-0178, NCT-00039598]
FX The work of Drs. McMaster, Loud, Rosenberg and Greene has been funded by
the Intramural Research Program of the National Cancer Institute. Ms.
Bracci's work is funded by contract support through the Intramural
Research Program of the National Cancer Institute (NCI protocol
02-C-0178, NCT-00039598).
NR 51
TC 1
Z9 1
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2045-7634
J9 CANCER MED-US
JI Cancer Med.
PD JUL
PY 2015
VL 4
IS 7
BP 1069
EP 1078
DI 10.1002/cam4.450
PG 10
WC Oncology
SC Oncology
GA CM7TJ
UT WOS:000357899100012
PM 25882629
ER
PT J
AU Ma, HY
Xu, XX
Ursin, G
Simon, MS
Marchbanks, PA
Malone, KE
Lu, YN
McDonald, JA
Folger, SG
Weiss, LK
Sullivan-Halley, J
Deapen, DM
Press, MF
Bernstein, L
AF Ma, Huiyan
Xu, Xinxin
Ursin, Giske
Simon, Michael S.
Marchbanks, Polly A.
Malone, Kathleen E.
Lu, Yani
McDonald, Jill A.
Folger, Suzanne G.
Weiss, Linda K.
Sullivan-Halley, Jane
Deapen, Dennis M.
Press, Michael F.
Bernstein, Leslie
TI Reduced risk of breast cancer associated with recreational physical
activity varies by HER2 status
SO CANCER MEDICINE
LA English
DT Article
DE Breast cancer; ER; HER2; luminal A breast cancer; p53; physical
activity; PR; Triple-negative breast cancer
ID HORMONE-RECEPTOR STATUS; ESTROGEN-RECEPTOR; REPRODUCTIVE EXPERIENCES;
PROGESTERONE-RECEPTOR; P53 MUTATIONS; UNITED-STATES; WHITE WOMEN;
BODY-SIZE; GENE; EXPRESSION
AB Convincing epidemiologic evidence indicates that physical activity is inversely associated with breast cancer risk. Whether this association varies by the tumor protein expression status of the estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), or p53 is unclear. We evaluated the effects of recreational physical activity on risk of invasive breast cancer classified by the four biomarkers, fitting multivariable unconditional logistic regression models to data from 1195 case and 2012 control participants in the population-based Women's Contraceptive and Reproductive Experiences Study. Self-reported recreational physical activity at different life periods was measured as average annual metabolic equivalents of energy expenditure [MET]-hours per week. Our biomarker-specific analyses showed that lifetime recreational physical activity was negatively associated with the risks of ER-positive (ER+) and of HER2-negative (HER2-) subtypes (both P(trend)0.04), but not with other subtypes (all P-trend>0.10). Analyses using combinations of biomarkers indicated that risk of invasive breast cancer varied only by HER2 status. Risk of HER2-breast cancer decreased with increasing number of MET-hours of recreational physical activity in each specific life period examined, although some trend tests were only marginally statistically significant (all P(trend)0.06). The test for homogeneity of trends (HER2- vs. HER2+) reached statistical significance only when evaluating physical activity during the first 10years after menarche (P-homogeneity=0.03). Our data suggest that physical activity reduces risk of invasive breast cancers that lack HER2 overexpression, increasing our understanding of the biological mechanisms by which physical activity acts.
C1 [Ma, Huiyan; Xu, Xinxin; Lu, Yani; Sullivan-Halley, Jane; Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Div Canc Etiol, Duarte, CA 91010 USA.
[Ursin, Giske] Canc Registry Norway, N-0304 Oslo, Norway.
[Ursin, Giske] Univ Oslo, Inst Basic Med Sci, Dept Nutr, Oslo, Norway.
[Simon, Michael S.] Wayne State Univ, Karmanos Canc Inst, Dept Oncol, Detroit, MI 48201 USA.
[Marchbanks, Polly A.; Folger, Suzanne G.] Ctr Dis Control & Prevent, Div Reprod Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA.
[Malone, Kathleen E.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
[McDonald, Jill A.] New Mexico State Univ, Coll Hlth & Social Serv, Las Cruces, NM 88003 USA.
[Weiss, Linda K.] NCI, Canc Ctr Branch, Bethesda, MD 20850 USA.
[Ursin, Giske; Deapen, Dennis M.] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Press, Michael F.] Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA.
RP Ma, HY (reprint author), City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Div Canc Etiol, 1500 E Duarte Rd, Duarte, CA 91010 USA.
EM hma@coh.org
FU National Institute for Child Health and Human Development
[N01-HD-3-3175]; National Cancer Institute [K05-CA136967]; National
Cancer Institute of the National Institutes of Health [R03CA188549];
National Cancer Institute, NIH; Fred Hutchinson Cancer Research Center
[N01-HD-2-3166]; Karmanos Cancer Institute at Wayne State University
[N01-HD-3-3174]; University of Pennsylvania [N01-HD-3-3276]; University
of Southern California [N01-HD-3-3175]; Centers for Disease Control and
Prevention [Y01-HD-7022]; California Department of Health Services;
National Institute of Child Health and Human Development
[N01-HD-3-3175]; Breast Cancer Research Foundation (MFPress); Emory
University [N01-HD-3-3168]; [N01-CN65064]; [N01-PC-67010]
FX This work was supported by the National Institute for Child Health and
Human Development grant N01-HD-3-3175, National Cancer Institute grant
K05-CA136967, and the National Cancer Institute of the National
Institutes of Health under Award Number R03CA188549. Data collection for
the Women's CARE Study was supported by the National Institute of Child
Health and Human Development and National Cancer Institute, NIH, through
contracts with Emory University (N01-HD-3-3168), Fred Hutchinson Cancer
Research Center (N01-HD-2-3166), Karmanos Cancer Institute at Wayne
State University (N01-HD-3-3174), University of Pennsylvania
(N01-HD-3-3276), and University of Southern California (N01-HD-3-3175)
and Interagency Agreement with Centers for Disease Control and
Prevention (Y01-HD-7022). Collection of cancer incidence data in LA
County by University of Southern California was supported by California
Department of Health Services as part of the statewide cancer reporting
program mandated by California Health and Safety Code, Section 103885.
Support for use of SEER cancer registries through contracts N01-CN65064
(Detroit) and N01-PC-67010 (LA). Biomarker determination and analyses
were supported by a contract from the National Institute of Child Health
and Human Development (N01-HD-3-3175) and a grant from the Breast Cancer
Research Foundation (MFPress).
NR 59
TC 3
Z9 3
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2045-7634
J9 CANCER MED-US
JI Cancer Med.
PD JUL
PY 2015
VL 4
IS 7
BP 1122
EP 1135
DI 10.1002/cam4.465
PG 14
WC Oncology
SC Oncology
GA CM7TJ
UT WOS:000357899100017
PM 25924995
ER
PT J
AU Boyle, EB
Deziel, NC
Specker, BL
Collingwood, S
Weisel, CP
Wright, DJ
Dellarco, M
AF Boyle, Elizabeth Barksdale
Deziel, Nicole C.
Specker, Bonny L.
Collingwood, Scott
Weisel, Clifford P.
Wright, David J.
Dellarco, Michael
TI Feasibility and informative value of environmental sample collection in
the National Children's Vanguard Study
SO ENVIRONMENTAL RESEARCH
LA English
DT Article
DE Birth cohort study; Air samples; Water samples; Wipe samples; National
Children's Study
ID DISINFECTION BY-PRODUCTS; DISEASE PREVENTION RESEARCH; VOLATILE
ORGANIC-COMPOUNDS; VOLUME SURFACE SAMPLER; EUROPEAN BIRTH COHORTS;
CARPET DUST SAMPLES; EXPOSURE ASSESSMENT; DRINKING-WATER; EXHALED
BREATH; UNITED-STATES
AB Background: Birth cohort studies provide the opportunity to advance understanding of the impact of environmental factors on childhood health and development through prospective collection of environmental samples.
Methods: We evaluated the feasibility and informative value of the environmental sample collection methodology in the initial pilot phase of the National Children's Study, a planned U.S. environmental birth cohort study. Environmental samples were collected from January 2009-September 2010 at up to three home visits: pre-pregnancy (n=306), pregnancy (n=807), and 6-months postnatal (n=117). Collections included air for particulate matter <= 2.5 mu m (PM2.5), nitrogen dioxide, ozone, volatile organic compounds (VOCs), and carbonyls; vacuum dust for allergens/endotoxin; water for VOCs, trihalo-methanes (THMs), and haloacetic acids (HAAs); and wipe samples for pesticides, semi-volatile organics, and metals. We characterized feasibility using sample collection rates and times and informative value using analyte detection frequencies (DF).
Results: Among the 1230 home visits, environmental sample collection rates were high across all sample types (mean=89%); all samples except the air PM2.5 samples had collection times <30 min. Informative value was low for water VOCs (median DF=0%) and pesticide floor wipes (median DF=5%). Informative value was moderate for air samples (median DF=35%) and high for water THMs and HAAs (median DF=91% and 75%, respectively).
Conclusions: Though collection of environmental samples was feasible, some samples (e.g., wipe pesticides and water VOCs) yielded limited information. These results can be used in conjunction with other study design considerations, such as target population size and hypotheses of interest, to inform the method selection of future environmental health birth cohort studies. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Boyle, Elizabeth Barksdale; Wright, David J.] Westat Corp, Rockville, MD USA.
[Deziel, Nicole C.] Yale Univ, Sch Publ Hlth, Dept Environm Hlth Sci, New Haven, CT USA.
[Specker, Bonny L.] S Dakota State Univ, Ethel Austin Martin Program Human Nutr, Brookings, SD 57007 USA.
[Collingwood, Scott] Univ Utah, Dept Pediat, Salt Lake City, UT USA.
[Weisel, Clifford P.] Rutgers State Univ, EOHSI, Piscataway, NJ USA.
[Dellarco, Michael] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Boyle, EB (reprint author), Natl Acad Sci, Board Environm Studies & Toxicol Natl Res Council, 500 Fifth St NW 618, Washington, DC 20001 USA.
EM eboyle@nas.edu
OI Boyle, Elizabeth/0000-0002-9412-7998; Specker, Bonny/0000-0003-4759-9957
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD); Office of the Director of the National Institutes
of Health; NICHD [GS-234-8144H]
FX This manuscript, a 'primary NCS publication', was developed by a Writing
Team assembled by the NCS Publications Committee for the purpose of
sharing centrally collected NCS data. The analysis was conducted as part
of the National Children's Study, supported by the Eunice Kennedy
Shriver National Institute of Child Health and Human Development
(NICHD), and funded, through its appropriation, by the Office of the
Director of the National Institutes of Health. Supported in part by
NICHD Contract no. GS-234-8144H. The authors thank Ms. Asia Khan, Jane
Xue, and Jane Stevens for SAS programming, and Rebecca Jeffries Birch
and Dr. Maire Heikkinen for technical expertise. We also thank the
participants of the National Children's Study Vanguard Study.
NR 60
TC 3
Z9 3
U1 2
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0013-9351
EI 1096-0953
J9 ENVIRON RES
JI Environ. Res.
PD JUL
PY 2015
VL 140
BP 345
EP 353
DI 10.1016/j.envres.2015.04.006
PG 9
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health
GA CM7VH
UT WOS:000357904100038
PM 25913153
ER
PT J
AU Papadopoulou, E
Haug, LS
Sabaredzovic, A
Eggesbo, M
Longnecker, MP
AF Papadopoulou, Eleni
Haug, Line S.
Sabaredzovic, Azemira
Eggesbo, Merete
Longnecker, Matthew P.
TI Reliability of perfluoroalkyl substances in plasma of 100 women in two
consecutive pregnancies
SO ENVIRONMENTAL RESEARCH
LA English
DT Article
DE Pregnancy; Perfluoroalkyl substances; PFOS; Correlations; MoBa
ID NATIONAL BIRTH COHORT; PERFLUORINATED COMPOUNDS; POLYFLUOROALKYL
SUBSTANCES; NORWEGIAN MOTHER; CHILD COHORT; SERUM CONCENTRATIONS;
PRODUCTION WORKERS; ALKYL SUBSTANCES; DRINKING-WATER; HUMAN EXPOSURE
AB The potential toxicity of background exposure to perfluoroalkyl substances (PFASs) is currently under active investigation. Such investigations typically rely on a single measure of PFAS concentration, yet the longer-term reliability of a single measure has not been well characterized, especially among reproductive-aged women. Our aim was to investigate the association between PFAS plasma concentrations of 100 women in two consecutive pregnancies and explore changes in plasma concentration related to reproductive factors. The women in our study were enrolled in the Norwegian Mother and Child Cohort Study (MoBa) from 2003 to 2009. About half of them breastfed exclusively for 6 months and the rest of the participants did not breastfeed between the two consecutive pregnancies (median time between pregnancies: 18 months). Maternal blood was collected at mid-pregnancy and plasma was analyzed for 10 PFASs. Statistical analyses were restricted to 6 PFASs that were quantifiable in more than 80% of the samples. We estimated the correlation between repeated PFAS measurements, the percentage change between pregnancies and the effect of several reproductive factors in multivariate linear regression models of PFAS concentrations in the second pregnancy. The Pearson correlation coefficient between repeated PFAS measurements was, for perfluorooctane sulfonate (PFOS), 0.80; perfluorooctanoate (PFOA), 0.50; perfluorohexane sulfonate (PFHxS), 0.74; perfluorononanoate (PFNA), 0.39; perfluoroundecanoate (PFUnDA), 0.71; and perfluorodecanoate (PFDA), 0.60. Adjustment for maternal age, delivery year, and time and breastfeeding between pregnancies did not substantially affect the observed correlations. We found 44-47% median reductions in the concentrations of PFOS, PFOA and PFHxS between pregnancies, while the change in concentrations between pregnancies was smaller and more variable for PFNA, PFUnDA and PFDA. The variation in plasma concentrations in the second pregnancy was mainly accounted for by the concentration in the first pregnancy; for PFOS, PFOA, and PFNA, breastfeeding also accounted for a substantial proportion. In conclusion, we found the reliability of PFAS measurements in maternal plasma to be moderate to high, and in these data, several factors, especially breastfeeding, were related to plasma concentrations. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Papadopoulou, Eleni; Haug, Line S.; Sabaredzovic, Azemira] Norwegian Inst Publ Hlth, Div Environm Med, N-0456 Oslo, Norway.
[Eggesbo, Merete] Norwegian Inst Publ Hlth, Div Epidemiol, N-0473 Oslo, Norway.
[Longnecker, Matthew P.] NIEHS, Epidemiol Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
RP Papadopoulou, E (reprint author), Norwegian Inst Publ Hlth, Div Environm Med, POB 4404, NO-0403 Oslo, Norway.
EM eleni.papadopoulou@fhi.no
OI PAPADOPOULOU, ELENI/0000-0001-7034-5897; Longnecker,
Matthew/0000-0001-6073-5322; Eggesbo, Merete/0000-0002-0006-5336
FU Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences; Norwegian Ministry of Health; NIH/NINDS
[1 UO1 NS 047537-01, 2 UO1 NS 047537-06A1]; Norwegian Research
Council/FUGE [151918/S10]; Ministry of Education and Research; NIH/NIEHS
[N01-ES-75558]
FX This research was supported in part by the Intramural Research Program
of the NIH, National Institute of Environmental Health Sciences. The
Norwegian Mother and Child Cohort Study is supported by the Norwegian
Ministry of Health and the Ministry of Education and Research, NIH/NIEHS
(contract no. N01-ES-75558), NIH/NINDS (Grant no. 1 UO1 NS 047537-01,
Grant no. 2 UO1 NS 047537-06A1), and the Norwegian Research Council/FUGE
(Grant no. 151918/S10).
NR 59
TC 6
Z9 6
U1 4
U2 22
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0013-9351
EI 1096-0953
J9 ENVIRON RES
JI Environ. Res.
PD JUL
PY 2015
VL 140
BP 421
EP 429
DI 10.1016/j.envres.2015.04.022
PG 9
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health
GA CM7VH
UT WOS:000357904100047
PM 25957838
ER
PT J
AU Zhu, YY
Zhang, CL
Liu, DP
Grantz, KL
Wallace, M
Mendola, P
AF Zhu, Yeyi
Zhang, Cuilin
Liu, Danping
Grantz, Katherine L.
Wallace, Maeve
Mendola, Pauline
TI Maternal ambient air pollution exposure preconception and during early
gestation and offspring congenital orofacial defects
SO ENVIRONMENTAL RESEARCH
LA English
DT Article
DE Air pollution; Preconception exposure; Organogenesis; Cleft palate;
Cleft lip
ID BIRTH-DEFECTS; CARBON-MONOXIDE; ORAL CLEFTS; ANOMALIES; RISK; PREGNANCY;
METAANALYSIS; QUALITY; POLLUTANTS; CALIFORNIA
AB Background: Maternal air pollution exposure has been related to orofacial clefts but the literature is equivocal. Potential chronic preconception effects have not been studied. Objectives: Criteria air pollutant exposure during three months preconception and gestational weeks 3-8 was studied in relation to orofacial defects.
Methods: Among 188,102 live births and fetal deaths from the Consortium on Safe Labor (2002-2008), 63 had isolated cleft palate (CP) and 159 had isolated cleft lip with or without cleft palate (CL +/- CP). Exposures were estimated using a modified Community Multiscale Air Quality model. Logistic regression with generalized estimating equations adjusted for site/region and maternal demographic, lifestyle and clinical factors calculated the odds ratio (OR) and 95% CI per interquartile increase in each pollutant.
Results: Preconception, carbon monoxide (CO; OR=2.24; CI: 1.21, 4.16) and particulate matter (PM) <= 10 mu m (OR=1.72; CI: 1.12, 2.66) were significantly associated with CP, while sulfur dioxide (SO2) was associated with CL +/- CP (OR=1.93; Cl: 1.16, 3.21). During gestational weeks 3-8, CO remained a significant risk for CP (OR=2.74; Cl: 1.62, 4.62) and nitrogen oxides (NOx; OR=3.64; CI: 1.73, 7.66) and PM <= 2.5 mu m (PM2.5; OR=1.74; Cl: 1.15, 2.64) were also related to the risk. Analyses by individual week revealed that positive associations of NOx and PM2.5 with CP were most prominent from weeks 3-6 and 3-5, respectively.
Conclusions: Exposure to several criteria air pollutants preconception and during early gestation was associated with elevated odds for CP, while CL +/- CP was only associated with preconception SO2 exposure. Published by Elsevier Inc.
C1 [Zhu, Yeyi; Zhang, Cuilin; Grantz, Katherine L.; Wallace, Maeve; Mendola, Pauline] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Epidemiol Branch, Rockville, MD 20852 USA.
[Liu, Danping] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Biostat & Bioinformat Branch, Rockville, MD USA.
RP Mendola, P (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Epidemiol Branch, Rockville, MD 20852 USA.
EM pauline.mendola@nih.gov
OI Mendola, Pauline/0000-0001-5330-2844; Grantz,
Katherine/0000-0003-0276-8534
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health [HHSN267200603425C, HHSN275200800002I, HHSN27500008]
FX This work was supported by the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health; including Contract No.
HHSN267200603425C (Consortium on Safe Labor), Contract No.
HHSN275200800002I, and Task Order No. HHSN27500008 (Air Quality and
Reproductive Health).
NR 40
TC 3
Z9 3
U1 1
U2 10
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0013-9351
EI 1096-0953
J9 ENVIRON RES
JI Environ. Res.
PD JUL
PY 2015
VL 140
BP 714
EP 720
DI 10.1016/j.envres.2015.06.002
PG 7
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health
GA CM7VH
UT WOS:000357904100082
PM 26099933
ER
PT J
AU Dobrovolskaia, MA
McNeil, SE
AF Dobrovolskaia, Marina A.
McNeil, Scott E.
TI Strategy for selecting nanotechnology carriers to overcome immunological
and hematological toxicities challenging clinical translation of nucleic
acid-based therapeutics
SO EXPERT OPINION ON DRUG DELIVERY
LA English
DT Review
DE drug delivery; immunotoxicity; nanoparticles; nucleic acid therapeutics
ID IN-VITRO EFFICACY; PHASE-II TRIAL; SIRNA DELIVERY; DRUG-DELIVERY;
TARGETED DELIVERY; IMMUNOMODULATORY OLIGONUCLEOTIDES; ANTISENSE
OLIGONUCLEOTIDE; CANCER-CHEMOTHERAPY; GOLD NANOPARTICLES; RNA
NANOPARTICLES
AB Introduction: Clinical translation of nucleic acid-based therapeutics (NATs) is hampered by assorted challenges in immunotoxicity, hematotoxicity, pharmacokinetics, toxicology and formulation. Nanotechnology-based platforms are being considered to help address some of these challenges due to the nanoparticles' ability to change drug biodistribution, stability, circulation half-life, route of administration and dosage. Addressing toxicology and pharmacology concerns by various means including NATs reformulation using nanotechnology-based carriers has been reviewed before. However, little attention was given to the immunological and hematological issues associated with nanotechnology reformulation.
Areas covered: This review focuses on application of nanotechnology carriers for delivery of various types of NATs, and how reformulation using nanoparticles affects immunological and hematological toxicities of this promising class of therapeutic agents.
Expert opinion: NATs share several immunological and hematological toxicities with common nanotechnology carriers. In order to avoid synergy or exaggeration of undesirable immunological and hematological effects of NATs by a nanocarrier, it is critical to consider the immunological compatibility of the nanotechnology platform and its components. Since receptors sensing nucleic acids are located essentially in all cellular compartments, a strategy for developing a nanoformulation with reduced immunotoxicity should first focus on precise delivery to the target site/cells and then on optimizing intracellular distribution.
C1 [Dobrovolskaia, Marina A.] Leidos Biomed Res Inc, Nanotechnol Characterizat Lab, Frederick Natl Lab Canc Res, Immunol Sect, Frederick, MD 21702 USA.
[McNeil, Scott E.] Leidos Biomed Res Inc, Nanotechnol Characterizat Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
RP Dobrovolskaia, MA (reprint author), Leidos Biomed Res Inc, Nanotechnol Characterizat Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
EM marina@mail.nih.gov
RI Nanotechnology Characterization Lab, NCL/K-8454-2012
FU Frederick National Laboratory for Cancer Research, National Institutes
of Health [HHSN261200800001E]
FX 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. The authors have no other relevant affiliations or financial
involvement with any organization or entity with a financial interest in
or financial conflict with the subject matter or materials discussed in
the manuscript apart from those disclosed.
NR 122
TC 10
Z9 10
U1 0
U2 19
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1742-5247
EI 1744-7593
J9 EXPERT OPIN DRUG DEL
JI Expert Opin. Drug Deliv.
PD JUL
PY 2015
VL 12
IS 7
BP 1163
EP 1175
DI 10.1517/17425247.2015.1042857
PG 13
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CM5XK
UT WOS:000357762100010
PM 25994601
ER
PT J
AU Ellefsen, KN
Concheiro, M
Suzuki, M
Rice, KC
Elmore, JS
Baumann, MH
Huestis, MA
AF Ellefsen, Kayla N.
Concheiro, Marta
Suzuki, Masaki
Rice, Kenner C.
Elmore, Joshua S.
Baumann, Michael H.
Huestis, Marilyn A.
TI Quantification of methylone and metabolites in rat and human plasma by
liquid chromatography-tandem mass spectrometry
SO FORENSIC TOXICOLOGY
LA English
DT Article
DE Methylone; Synthetic cathinones; Novel designer drugs; Metabolites;
4-Hydroxy-3-methoxymethcathinone; LC-MS/MS
ID SYNTHETIC CATHINONES; BATH SALTS; DESIGNER DRUG; UNITED-STATES;
IN-VITRO; MEPHEDRONE; ABUSE; DEATH; MDPV
AB Methylone is a commonly abused synthetic cathinone derivative marketed as a "legal" alternative to "ecstasy" or cocaine. Previous studies examined the metabolism of methylone in vitro and in vivo; 4-hydroxy-3-methoxymethcathinone (HMMC) was identified as the primary metabolite, with other reported minor metabolites, 3,4-methylenedioxycathinone (MDC) and 3,4-dihydroxymethcathinone (HHMC). However, limited information is known about methylone and its metabolites' pharmacokinetics. We developed and fully validated a method for the simultaneous quantification of methylone, HMMC, MDC and HHMC by liquid chromatography-tandem mass spectrometry in 100 A mu l rat and human plasma. beta-Glucuronidase was utilized for plasma hydrolysis, followed by perchloric acid protein precipitation and solid-phase extraction utilizing cation exchange columns. Chromatographic separation was performed with a Synergi Polar column in gradient mode, and analytes were determined by two multiple reaction monitoring (MRM) transitions. Linear ranges of 0.5-1,000 A mu g/l (methylone, HMMC and MDC) and 10-1,000 A mu g/l (HHMC) were achieved. Bias and imprecision were generally acceptable, although quantification of HHMC exhibited variability (16.2-37 %). Extraction efficiencies and ion suppression were 89.9-104 % (for HHMC, 15.9-16.2 %) and < 11.4 %, respectively. Methylone and metabolites were stable in plasma for 24 h at room temperature, 72 h at 4 A degrees C, and after three freeze-thaw cycles (except for a 60 % HMMC increase). Human and rat plasma were cross-validated, documenting that rat plasma quality control samples were accurately quantified against a human plasma calibration curve (-23.8 to 12 % bias). As proof of method, rat plasma specimens were analyzed pre-injection and after subcutaneous administration of methylone at 6 mg/kg from 15 to 480 min post-dosing. Methylone, HMMC, MDC and HHMC concentrations ranged from 1.1 to 1,310, 11.2 to 194, 1.9 to 152 and 24.7 to 188 A mu g/l, respectively.
C1 [Ellefsen, Kayla N.; Concheiro, Marta; Huestis, Marilyn A.] NIDA, Chem & Drug Metab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Ellefsen, Kayla N.] Univ Maryland, Toxicol Program, Baltimore, MD 21201 USA.
[Suzuki, Masaki; Rice, Kenner C.] NIDA, Drug Design & Synth Sect, Intramural Res Program, Baltimore, MD 21224 USA.
[Suzuki, Masaki; Rice, Kenner C.] NIAAA, NIH, Baltimore, MD USA.
[Elmore, Joshua S.; Baumann, Michael H.] NIDA, Designer Drug Res Unit, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Huestis, MA (reprint author), NIDA, Chem & Drug Metab, Intramural Res Program, NIH, 251 Bayview Blvd,Suite 200 Room 05A 721, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
FU National Institute on Drug Abuse (NIDA); National Institute on Alcohol
Abuse and Alcoholism (NIAAA), National Institutes of Health (NIH)
FX This research was supported by the Intramural Research Program of the
National Institute on Drug Abuse (NIDA), and the National Institute on
Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health
(NIH).
NR 35
TC 2
Z9 2
U1 4
U2 35
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1860-8965
EI 1860-8973
J9 FORENSIC TOXICOL
JI Forensic Toxicol.
PD JUL
PY 2015
VL 33
IS 2
BP 202
EP 212
DI 10.1007/s11419-015-0263-z
PG 11
WC Toxicology
SC Toxicology
GA CM9UU
UT WOS:000358055400003
ER
PT J
AU Newmeyer, MN
Concheiro, M
da Costa, JL
LoDico, C
Gorelick, DA
Huestis, MA
AF Newmeyer, Matthew N.
Concheiro, Marta
da Costa, Jose Luiz
LoDico, Charles
Gorelick, David A.
Huestis, Marilyn A.
TI Simultaneous plasma and oral fluid morphine and codeine concentrations
after controlled administration of poppy seeds with known opiate content
SO FORENSIC TOXICOLOGY
LA English
DT Article
DE Oral fluid; Plasma; Poppy seeds; Morphine; Codeine
ID URINE; INGESTION; DRUGS; SERUM
AB Opiates are included in drug testing programs because of their psychoactive properties and abuse potential, but excluding poppy seed ingestion is necessary to correctly interpret positive opiate results. There are few available data for plasma and oral fluid (OF) following poppy seed ingestion, and most do not report opiate content in the ingested poppy seeds. We quantified plasma and OF morphine and codeine concentrations via a fully validated liquid chromatography-tandem mass spectrometry method after controlled administration of two doses (8 h apart) of raw, uncooked poppy seeds (45-g) each containing 15.7 mg of morphine and 3.1 mg of codeine. Simultaneous specimens were collected before and up to 32 h after the first dose. Maximum OF morphine and codeine concentrations (3.6-110 and 2.1-22.4 A mu g/l, respectively) were significantly greater than simultaneously collected maximum plasma concentrations (2.8-9.3 and 1.1-2.0 A mu g/l, respectively). OF and plasma morphine and codeine concentrations were significantly correlated, but large variabilities preclude plasma concentration estimations from OF results. The median OF morphine time of first detection (t (first)) and time of last detection (t (last)) were both 0.5 h with cutoffs from 20 to 40 A mu g/l, with 0.9-6.7 % positive specimens. Codeine was detected only at low 15-20 A mu g/l OF cutoffs; median t (first) and t (last) were 0.5-1.3 h and 0.5-2.3 h, respectively, with only 0.4-1.8 % specimens positive. After two large, raw, uncooked poppy seed doses, significant differences between plasma and OF opiate pharmacokinetics were observed. Less than 6.7 % positive OF tests and a median morphine OF detection time of only 0.5 h with cutoffs from 20 to 40 A mu g/l suggest that few OF positive morphine tests can be explained by poppy seed ingestion.
C1 [Newmeyer, Matthew N.; Concheiro, Marta; da Costa, Jose Luiz; Gorelick, David A.; Huestis, Marilyn A.] NIDA, Chem & Drug Metab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Newmeyer, Matthew N.] Univ Maryland, Toxicol Program, Baltimore, MD 21201 USA.
[LoDico, Charles] US Dept HHS, Div Workplace Programs, Subst Abuse Mental Hlth Serv Adm, Rockville, MD USA.
RP Huestis, MA (reprint author), NIDA, Chem & Drug Metab, Intramural Res Program, NIH, 251 Bayview Blvd,Suite 200 Room 05A-721, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
RI Costa, Jose/C-1741-2012;
OI Costa, Jose/0000-0001-9954-0899; Newmeyer, Matthew/0000-0002-0653-1553
FU National Institute on Drug Abuse, National Institutes of Health;
Substance Abuse and Mental Health Services Administration
FX Funding was provided by the Intramural Research Program, National
Institute on Drug Abuse, National Institutes of Health, and the
Substance Abuse and Mental Health Services Administration. We
acknowledge contributions by the clinical staff of the NIDA IRP,
Behavioral Pharmacology Research Unit, and Clinical Research Unit, Johns
Hopkins Bayview Medical Center; and the Graduate Partnership Program,
NIH. The authors also thank Megan Taylor, Clinical Protocol Coordinator,
Chemistry and Drug Metabolism, NIDA IRP, for her valuable assistance.
NR 14
TC 0
Z9 0
U1 2
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1860-8965
EI 1860-8973
J9 FORENSIC TOXICOL
JI Forensic Toxicol.
PD JUL
PY 2015
VL 33
IS 2
BP 235
EP 243
DI 10.1007/s11419-015-0266-9
PG 9
WC Toxicology
SC Toxicology
GA CM9UU
UT WOS:000358055400006
ER
PT J
AU Hartman, RL
Anizan, S
Jang, M
Brown, TL
Yun, KM
Gorelick, DA
Milavetz, G
Spurgin, A
Gaffney, G
Huestis, MA
AF Hartman, Rebecca L.
Anizan, Sebastien
Jang, Moonhee
Brown, Timothy L.
Yun, Keming
Gorelick, David A.
Milavetz, Gary
Spurgin, Andrew
Gaffney, Gary
Huestis, Marilyn A.
TI Cannabinoid disposition in oral fluid after controlled vaporizer
administration with and without alcohol
SO FORENSIC TOXICOLOGY
LA English
DT Article
DE Cannabis; Alcohol; Vaporizer; Oral Fluid; On-site
ID CONTROLLED SMOKED CANNABIS; DRUG SCREENING DEVICES; PHARMACOKINETIC
PROPERTIES; MARIJUANA SMOKING; PERFORMANCE; DRIVERS; USERS; THC;
ETHANOL; PLASMA
AB Oral fluid (OF) is an advantageous matrix for cannabis detection, with on-site tests available for roadside drug-impaired driver screening. Limited data exist for device performance following consumption of vaporized cannabis, which reduces exposure to harmful combustion by-products. We assessed cannabinoid OF disposition, with and without alcohol, and evaluated on-site Drager(A (R)) DrugTest 5000 performance (Drager) following controlled vaporization of cannabis. Forty-three cannabis smokers (a parts per thousand yen1x/3 months, a parts per thousand currency sign3 days/week) reported 10-16 h prior to dosing, and drank placebo or low-dose alcohol [target similar to 0.065 % peak breath-alcohol concentration (BrAC)] 10 min prior to inhaling 500 mg of placebo, low-dose [2.9 % a dagger(9)-tetrahydrocannabinol (THC)], or high-dose (6.7 % THC) vaporized cannabis (within-subjects; six possible alcohol-cannabis combinations; 19 completers). BrAC readings and OF (Quantisal (TM), Drager) were collected before and up to 8.3 h post-dose. Median [range] maximum OF concentrations (C (max)) for low and high doses (no alcohol, N = 19) were 848 [32.1-18,230] and 764 [25.1-23,680] A mu g/l THC; 6.0 [0-100] and 26.8 [1.0-1106] A mu g/l cannabidiol; 54.4 [1.8-941] and 29.7 [0-766] A mu g/l cannabinol; and 24.1 [0-686] and 18.0 [0-414] ng/l 11-nor-9-carboxy-THC (THCCOOH). Lack of significant differences in THC concentration between low doses and high doses indicated that participants may have titrated doses. THC, cannabidiol and cannabinol C (max) values were immediately post-inhalation, but metabolite THCCOOH t (max) showed interindividual variability. Concurrent alcohol did not affect OF cannabinoid concentrations or on-site test sensitivity. With a THC confirmation cutoff of 5 A mu g/l, Drager sensitivity, specificity, and efficiency were 60.8, 98.2, and 82.5 %. Drager had lower sensitivity after 6.7 % THC vaporization (53.8 %, THC a parts per thousand yen2 A mu g/l confirmation cutoff) than reported following smoking a 6.8 % THC cigarette, but high specificity (99.3 %) and comparable efficiency (65.0 %). Vaporized THC bioavailability may be lower than that when smoked. Confirmation cutoff, time course, intake histories, and additional cannabinoid analytes also affect OF interpretation.
C1 [Hartman, Rebecca L.; Anizan, Sebastien; Jang, Moonhee; Yun, Keming; Gorelick, David A.; Huestis, Marilyn A.] NIDA, Chem & Drug Metab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Jang, Moonhee] Natl Forens Serv, Seoul, South Korea.
[Brown, Timothy L.] Univ Iowa, Natl Adv Driving Simulator, Iowa City, IA USA.
[Yun, Keming] Shanxi Med Univ, Sch Forens Med, Taiyuan, Peoples R China.
[Gorelick, David A.] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA.
[Milavetz, Gary; Spurgin, Andrew] Univ Iowa, Coll Pharm, Iowa City, IA 52242 USA.
[Gaffney, Gary] Univ Iowa, Carver Coll Med, Iowa City, IA USA.
RP Huestis, MA (reprint author), NIDA, Chem & Drug Metab, Intramural Res Program, NIH, 251 Bayview Blvd Ste 200 Rm 05A721, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
FU National Institute on Drug Abuse, NIH; United States Office of National
Drug Control Policy; National Highway Traffic Safety Administration
FX We thank the nurses and staff of the University of Iowa Clinical
Research Unit, as well as the staff of the National Advanced Driving
Simulator, for contributions to data collection. We further acknowledge
Cheryl Roe, Jennifer Henderson, Rose Schmitt, and Kayla Smith for data
assembly and coordination, and Allan J. Barnes for instrumentation
expertise. We acknowledge the University of Maryland, Baltimore
Toxicology Program, and the Graduate Partnership Program, National
Institutes of Health (NIH). The Drager DrugTest 5000, Quantisal, and
Volcano devices and supplies were provided by the manufacturers to NIH
through Materials Transfer Agreements. This research was funded by the
Intramural Research Program, National Institute on Drug Abuse, NIH, the
United States Office of National Drug Control Policy, and the National
Highway Traffic Safety Administration.
NR 64
TC 7
Z9 7
U1 3
U2 13
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1860-8965
EI 1860-8973
J9 FORENSIC TOXICOL
JI Forensic Toxicol.
PD JUL
PY 2015
VL 33
IS 2
BP 260
EP 278
DI 10.1007/s11419-015-0269-6
PG 19
WC Toxicology
SC Toxicology
GA CM9UU
UT WOS:000358055400008
ER
PT J
AU Castaneto, MS
Wohlfarth, A
Pang, SK
Zhu, MS
Scheidweiler, KB
Kronstrand, R
Huestis, MA
AF Castaneto, Marisol S.
Wohlfarth, Ariane
Pang, Shaokun
Zhu, Mingshe
Scheidweiler, Karl B.
Kronstrand, Robert
Huestis, Marilyn A.
TI Identification of AB-FUBINACA metabolites in human hepatocytes and urine
using high-resolution mass spectrometry
SO FORENSIC TOXICOLOGY
LA English
DT Article
DE AB-FUBINACA; Metabolite profiling; HRMS; Hepatocytes; In silico
ID HUMAN LIVER-MICROSOMES; IN-VITRO; SYNTHETIC CANNABINOIDS; LC-MS/MS;
STABILITY; DRUG; MIXTURES; PINACA; VIVO
AB AB-FUBINACA, N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(4-fluorobenzyl)-1H-indazole-3-carboxamide, is an indazole synthetic cannabinoid identified in drug seizures around the world. Few metabolism data are available, despite the need for human urinary markers to detect AB-FUBINACA intake. Our main objective was to identify suitable analytical targets by analyzing human hepatocyte incubation samples with high-resolution mass spectrometry (HRMS) and to confirm the results in authentic urine specimens. We also determined AB-FUBINACA's metabolic stability in human liver microsomes (HLMs) and compared hepatocyte and urine results with in silico predictions. The metabolic stability of AB-FUBINACA was determined in pooled HLMs (1 A mu mol/l, up to 1 h). The metabolite profile of human hepatocytes (10 A mu mol/l, 1 and 3 h) and urine samples from two subjects were determined by HRMS using information-dependent tandem-mass spectrometry (MS-MS) acquisition. Data were analyzed with MetabolitePilot (TM) software utilizing different processing algorithms, including generic peak finding, mass defect filtering, neutral loss, and product ion filtering. In silico metabolite prediction was performed with MetaSite (TM) software. AB-FUBINACA's half-life in HLMs was 62.6 +/- A 4.0 min. AB-FUBINACA produced 11 metabolites (2 glucuronides) in human hepatocytes and 10 were identified in authentic human urine. Major metabolic pathways were terminal amide hydrolysis, acyl glucuronidation and hydroxylation at the aminooxobutane moiety. Epoxidation followed by hydrolysis, hydroxylation at the indazole moiety and dehydrogenation were minor pathways. Defluorination did not occur. Seventeen first-generation metabolites were predicted in silico, of which seven were observed in vitro and eight in vivo. We recommend AB-FUBINACA carboxylic acid, hydroxy AB-FUBINACA carboxylic acid, dihydrodiol AB-FUBINACA and dihydrodiol AB-FUBINACA carboxylic acid as suitable urinary markers.
C1 [Castaneto, Marisol S.; Wohlfarth, Ariane; Scheidweiler, Karl B.; Huestis, Marilyn A.] NIDA, Chem & Drug Metab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Castaneto, Marisol S.] Univ Maryland, Sch Med, Toxicol Program, Baltimore, MD 21201 USA.
[Pang, Shaokun] SCIEX Ltd, Redwood City, CA USA.
[Zhu, Mingshe] Bristol Myers Squibb Co, Dept Biotransformat, Res & Dev, Princeton, NJ USA.
[Kronstrand, Robert] Linkoping Univ, Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden.
[Kronstrand, Robert] Linkoping Univ, Dept Med & Hlth Sci, Div Drug Res, Linkoping, Sweden.
RP Huestis, MA (reprint author), NIDA, Chem & Drug Metab, Intramural Res Program, NIH, 251 Bayview Blvd,Suite 200 Room 05A-721, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
FU National Institute on Drug Abuse, National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institute on Drug Abuse, National Institutes of Health.
AB-FUBINACA was generously donated by the US Drug Enforcement
Administration. Molecular Discovery Ltd kindly provided the MetaSite
(TM) software.
NR 33
TC 16
Z9 16
U1 3
U2 20
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1860-8965
EI 1860-8973
J9 FORENSIC TOXICOL
JI Forensic Toxicol.
PD JUL
PY 2015
VL 33
IS 2
BP 295
EP 310
DI 10.1007/s11419-015-0275-8
PG 16
WC Toxicology
SC Toxicology
GA CM9UU
UT WOS:000358055400010
ER
PT J
AU Mandava, A
Millum, J
Berkman, BE
AF Mandava, Amulya
Millum, Joseph
Berkman, Benjamin E.
TI When Should Genome Researchers Disclose MISATTRIBUTED PARENTAGE?
SO HASTINGS CENTER REPORT
LA English
DT Article
ID UNDIAGNOSED DISEASES; INCIDENTAL FINDINGS; PATERNITY; DISCOVERY
C1 [Mandava, Amulya] Harvard Univ, Sch Divin, Arts Candidate, Cambridge, MA 02138 USA.
[Mandava, Amulya; Berkman, Benjamin E.] NIH, Dept Bioeth, Bethesda, MD USA.
[Millum, Joseph] NIH, Ctr Clin, Dept Bioeth, Bethesda, MD USA.
[Millum, Joseph] NIH, Fogarty Int Ctr, Bethesda, MD USA.
[Berkman, Benjamin E.] NHGRI, Bethesda, MD USA.
RP Mandava, A (reprint author), Harvard Univ, Sch Divin, Arts Candidate, Cambridge, MA 02138 USA.
FU Intramural NIH HHS [Z99 CL999999]
NR 21
TC 2
Z9 2
U1 1
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0093-0334
EI 1552-146X
J9 HASTINGS CENT REP
JI Hastings Cent. Rep.
PD JUL-AUG
PY 2015
VL 45
IS 4
BP 28
EP 36
DI 10.1002/hast.452
PG 9
WC Ethics; Health Care Sciences & Services; Medical Ethics; Social
Sciences, Biomedical
SC Social Sciences - Other Topics; Health Care Sciences & Services; Medical
Ethics; Biomedical Social Sciences
GA CM6OH
UT WOS:000357807700013
PM 25677868
ER
PT J
AU Auer, PL
Nalls, M
Meschia, JF
Worrall, BB
Longstreth, WT
Seshadri, S
Kooperberg, C
Burger, KM
Carlson, CS
Carty, CL
Chen, WM
Cupples, LA
DeStefano, AL
Fornage, M
Hardy, J
Hsu, L
Jackson, RD
Jarvik, GP
Kim, DS
Lakshminarayan, K
Lange, LA
Manichaikul, A
Quinlan, AR
Singleton, AB
Thornton, TA
Nickerson, DA
Peters, U
Rich, SS
AF Auer, Paul L.
Nalls, Mike
Meschia, James F.
Worrall, Bradford B.
Longstreth, W. T., Jr.
Seshadri, Sudha
Kooperberg, Charles
Burger, Kathleen M.
Carlson, Christopher S.
Carty, Cara L.
Chen, Wei-Min
Cupples, L. Adrienne
DeStefano, Anita L.
Fornage, Myriam
Hardy, John
Hsu, Li
Jackson, Rebecca D.
Jarvik, Gail P.
Kim, Daniel S.
Lakshminarayan, Kamakshi
Lange, Leslie A.
Manichaikul, Ani
Quinlan, Aaron R.
Singleton, Andrew B.
Thornton, Timothy A.
Nickerson, Deborah A.
Peters, Ulrike
Rich, Stephen S.
CA Natl Heart Lung Blood Inst Exome S
TI Rare and Coding Region Genetic Variants Associated With Risk of Ischemic
Stroke The NHLBI Exome Sequence Project
SO JAMA NEUROLOGY
LA English
DT Article
ID TRANS-FATTY-ACIDS; PHOSPHODIESTERASE-4D GENE; CARDIOVASCULAR-DISEASE;
HEART-DISEASE; METAANALYSIS; POPULATION; HERITABILITY; INFLAMMATION;
CHOLESTEROL; EVOLUTION
AB IMPORTANCE Stroke is the second leading cause of death and the third leading cause of years of life lost. Genetic factors contribute to stroke prevalence, and candidate gene and genome-wide association studies (GWAS) have identified variants associated with ischemic stroke risk. These variants often have small effects without obvious biological significance. Exome sequencing may discover predicted protein-altering variants with a potentially large effect on ischemic stroke risk.
OBJECTIVE To investigate the contribution of rare and common genetic variants to ischemic stroke risk by targeting the protein-coding regions of the human genome.
DESIGN, SETTING, AND PARTICIPANTS The National Heart, Lung, and Blood Institute (NHLBI) Exome Sequencing Project (ESP) analyzed approximately 6000 participants from numerous cohorts of European and African ancestry. For discovery, 365 cases of ischemic stroke (small-vessel and large-vessel subtypes) and 809 European ancestry controls were sequenced; for replication, 47 affected sibpairs concordant for stroke subtype and an African American case-control series were sequenced, with 1672 cases and 4509 European ancestry controls genotyped. The ESP's exome sequencing and genotyping started on January 1, 2010, and continued through June 30, 2012. Analyses were conducted on the full data set between July 12, 2012, and July 13, 2013.
MAIN OUTCOMES AND MEASURES Discovery of new variants or genes contributing to ischemic stroke risk and subtype (primary analysis) and determination of support for protein-coding variants contributing to risk in previously published candidate genes (secondary analysis).
RESULTS We identified 2 novel genes associated with an increased risk of ischemic stroke: a protein-coding variant in PDE4DIP (rs1778155; odds ratio, 2.15; P = 2.63 x 10(-8)) with an intracellular signal transduction mechanism and in ACOT4 (rs35724886; odds ratio, 2.04; P = 1.24 x 10(-7)) with a fatty acid metabolism; confirmation of PDE4DIP was observed in affected sibpair families with large-vessel stroke subtype and in African Americans. Replication of protein-coding variants in candidate genes was observed for 2 previously reported GWAS associations: ZFHX3 (cardioembolic stroke) and ABCA1 (large-vessel stroke).
CONCLUSIONS AND RELEVANCE Exome sequencing discovered 2 novel genes and mechanisms, PDE4DIP and ACOT4, associated with increased risk for ischemic stroke. In addition, ZFHX3 and ABCA1 were discovered to have protein-coding variants associated with ischemic stroke. These results suggest that genetic variation in novel pathways contributes to ischemic stroke risk and serves as a target for prediction, prevention, and therapy.
C1 [Auer, Paul L.] Univ Wisconsin, Joseph J Zilber Sch Publ Hlth, Milwaukee, WI 53201 USA.
[Auer, Paul L.; Kooperberg, Charles; Carlson, Christopher S.; Carty, Cara L.; Hsu, Li; Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Nalls, Mike; Singleton, Andrew B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA.
[Worrall, Bradford B.] Univ Virginia, Dept Neurol, Charlottesville, VA 22908 USA.
[Longstreth, W. T., Jr.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA.
[Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Burger, Kathleen M.] George Washington Univ Hosp, Dept Neurol, Washington, DC USA.
[Chen, Wei-Min; Manichaikul, Ani; Quinlan, Aaron R.; Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA.
[Cupples, L. Adrienne; DeStefano, Anita L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA.
[Hardy, John] UCL, Dept Neurosci, Reta Lila Weston Inst, London, England.
[Jackson, Rebecca D.] Ohio State Univ, Dept Internal Med, Columbus, OH 43210 USA.
[Jarvik, Gail P.] Univ Washington, Dept Med, Seattle, WA USA.
[Kim, Daniel S.; Nickerson, Deborah A.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
[Lakshminarayan, Kamakshi] Univ Minnesota, Dept Neurol, Minneapolis, MN 55455 USA.
[Lange, Leslie A.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Thornton, Timothy A.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
RP Rich, SS (reprint author), Univ Virginia, Ctr Publ Hlth Genom, 3232 West Complex,POB 800717, Charlottesville, VA 22908 USA.
EM ssr4n@virginia.edu
RI Hardy, John/C-2451-2009; Singleton, Andrew/C-3010-2009;
OI Seshadri, Sudha/0000-0001-6135-2622; Turner, Emily/0000-0001-9040-9229
FU NHLBI [RC2 HL-103010, RC2 HL-102923, RC2 HL-102924, RC2 HL-102925, RC2
HL-102926, N01HC-55015, N01HC-55016, N01HC-55017, N01HC-55018,
N01HC-55019, N01HC-55020, N01HC-55021, HHSN268201200036C]; National
Institute on Aging [R01AG023629]; Intramural Research Program of the
National Institute on Aging [Z01-AG000954-7]; Cystic Fibrosis Foundation
[GIBSON07K0, KNOWLE00A0, OBSERV04K0, RDP R026]; NIH [R01-HL068890,
R02-HL095396, UL1-RR025014, 5R00-HG004316, U01-HL089897, U01-HL089856,
RC2-HL101779, RC2-HL066583, R01-HG004738, HR-46002, P50-HL084946,
K23-AR52742, F32-HL083714, RC2-HL101651, HL077916, HL-69197, HL-76285,
M01-RR07122]; The NHLBI [R01HL105756, R01HL103612, R01HL120393,
N01-HC95095, N01-HC48047, N01-HC48048, N01-HC48049, N01-HC48050,
N01-HC-25195, NS17950, AG08122, AG033193, N01HC-95170, N01HC-95171,
N01HC-95172]; NHLBI. [HHSN268201100046C, HHSN268201100001C,
HHSN268201100002C, HHSN268201100003C, HHSN268201100004C,
HHSN271201100004C, RC2-HL102924, N01HC55222, N01HC85079, N01HC85080,
N01HC85081, N01HC85082, N01HC85083, N01HC85086, U01HL080295,
R01HL087652]; The NHLBI. [HHSN268200800007C, N01-HC-95159, N01-HC-95160,
N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165,
N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, 024156];
[R01-NS39987]; [R01-NS42733]
FX Funding for GO ESP was provided by NHLBI grants RC2 HL-103010 (HeartGO),
RC2 HL-102923 (LungGO), and RC2 HL-102924 (Women's Health Initiative
Sequencing Project). The exome sequencing was performed through NHLBI
grants RC2 HL-102925 (BroadGO) and RC2 HL-102926 (SeattleGO). HeartGO
components and their support include Atherosclerosis Risk in Communities
(NHLBI contracts N01HC-55015, N01HC-55016, N01HC-55017, N01HC-55018,
N01HC-55019, N01HC-55020, and N01HC-55021); Cardiovascular Health Study
(NHLBI contracts HHSN268201200036C, HHSN268200800007C, N01HC55222,
N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, and
N01HC85086); and NHLBI grants U01HL080295, R01HL087652, R01HL105756,
R01HL103612, and R01HL120393, with additional contribution from the
National Institute of Neurological Disorders and Stroke. Additional
support was provided through R01AG023629 from the National Institute on
Aging. A full list of principal Cardiovascular Health Study
investigators and institutions can be found at CHS-NHLBI.org; Coronary
Artery Risk Development in Young Adults (NHLBI contracts N01-HC95095,
N01-HC48047, N01-HC48048, N01-HC48049, and N01-HC48050); Framingham
Heart Study (NHLBI contract N01-HC-25195 and grants NS17950, AG08122,
and AG033193); Jackson Heart Study (NHLBI contracts N01HC-95170,
N01HC-95171, and N01HC-95172); Multi-Ethnic Study of Atherosclerosis
(NHLBI contracts N01-HC-95159 through N01-HC-95169 and grant 024156).
The Siblings with Ischemic Stroke Study (grant R01-NS39987) and the
Ischemic Stroke Genetics Study (grant R01-NS42733) contributed
phenotypic data and DNA samples. Dr Nalls' participation in this
research was supported, in part, by the Intramural Research Program of
the National Institute on Aging (grant Z01-AG000954-7). Portions of this
study used the high-performance computational capabilities of the
Biowulf Linux cluster at the National Institutes of Health (NIH)
(http://biowulf.nih.gov). The Women's Health Initiative program is
funded by the NHLBI through contracts HHSN268201100046C,
HHSN268201100001C, HHSN268201100002C, HHSN268201100003C,
HHSN268201100004C, and HHSN271201100004C, and grant RC2-HL102924 for the
Women's Health Initiative Sequencing Project. LungGO components and
their support include Cystic Fibrosis Foundation (Cystic Fibrosis
Foundation grants GIBSON07K0, KNOWLE00A0, OBSERV04K0, and RDP R026), and
NIH (grants R01-HL068890, R02-HL095396, UL1-RR025014, and
5R00-HG004316); Chronic Obstructive Pulmonary Disease (COPDGene; NIH
grants U01-HL089897 and U01-HL089856), and the COPD Foundation through
contributions made to an industry advisory board comprising AstraZeneca,
Boehringer Ingelheim, Novartis, Pfizer, and Sunovian; Acute Lung Injury
(NIH grant RC2-HL101779); Lung Health Study (NIH grants RC2-HL066583,
R01-HG004738, and HR-46002); Pulmonary Arterial Hypertension (NIH grants
P50-HL084946, K23-AR52742, and F32-HL083714); and Asthma (NIH grants
RC2-HL101651, HL077916, HL-69197, HL-76285, and M01-RR07122).
NR 40
TC 11
Z9 11
U1 1
U2 12
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6149
EI 2168-6157
J9 JAMA NEUROL
JI JAMA Neurol.
PD JUL
PY 2015
VL 72
IS 7
BP 781
EP 788
DI 10.1001/jamaneurol.2015.0582
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA CM8EP
UT WOS:000357931000011
PM 25961151
ER
PT J
AU Iadarola, MJ
Sapio, MR
Mannes, AJ
AF Iadarola, Michael J.
Sapio, Matthew R.
Mannes, Andrew J.
TI A new splice of life for the mu-opioid receptor
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Editorial Material
ID MORPHINE-INDUCED ANALGESIA; KNOCKOUT MICE; SPINAL-CORD; FUNCTIONAL
EXPRESSION; MOLECULAR-CLONING; MESSENGER-RNA; DORSAL-HORN; RAT-BRAIN;
TOLERANCE; PRECURSOR
AB mu-Opioid agonists mediate their analgesic effect through GPCRs that are generated via alternate splicing of the Oprm1 transcript. While the majority of mu-opioids interact with receptors comprising the canonical 7 transmembrane (7TN) domain, a recently identified class of mu-opioids appears to require a 6TM domain variant. In this issue of the JCI, Lu and colleagues provide an in vivo proof-of-concept demonstration that a 6TM isoform of the p-opioid receptor can support functional analgesia in Oprm1-deficent animals. The 6TM isoform was pharmacologically distinct from the canonical 7TM mu-opioid receptor, and 6TM agonists had a reduced side effect profile, which confers a strong therapeutic advantage over standard opioid analgesics. The observations of Lu et al. extend the reach of opioid-receptor neurobiology and pharmacology into a new era of analgesic discovery. This advance emerges from a series of fundamental research analyses in which elements of the endogenous opioid system were frequently in the vanguard.
C1 [Iadarola, Michael J.; Sapio, Matthew R.; Mannes, Andrew J.] NIH, Dept Perioperat Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Iadarola, MJ (reprint author), DPM, Anesthesia Sect, Bldg 10,Room 2C401,10 Ctr Dr,MSC 1510, Bethesda, MD 20892 USA.
EM miadarol@cc.nih.gov
RI Sapio, Matthew/J-5096-2016
OI Sapio, Matthew/0000-0002-8855-5419
FU Intramural NIH HHS
NR 40
TC 0
Z9 0
U1 1
U2 4
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
EI 1558-8238
J9 J CLIN INVEST
JI J. Clin. Invest.
PD JUL
PY 2015
VL 125
IS 7
BP 2558
EP 2561
DI 10.1172/JCI82060
PG 4
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA CM3AK
UT WOS:000357553300003
PM 26011639
ER
PT J
AU Li, C
Krashes, MJ
AF Li, Chia
Krashes, Michael J.
TI Hypoactivity following perturbed estrogen signaling in the medial
amygdala
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Editorial Material
ID OVARIECTOMIZED RATS; FOOD-INTAKE; ENERGY HOMEOSTASIS; MICE; ESTRADIOL;
NEURONS; RECEPTORS; SEROTONIN; CIRCUIT; NUCLEUS
AB Activation of estrogen receptor alpha (ER alpha) in the brain prevents obesity as the result of increased energy expenditure and decreased food intake. While ERa is present on several neural populations, it is not clear how different regions of the brain mediate the weight-regulating effects of ERa activation. In this issue of the JCI, Xu and colleagues provide extensive evidence that ERa is abundant on neurons expressing single-minded-1 (SIM1) in the medial amygdala (MeA) and that loss of ERa in these cells enhances weight gain in both male and female mice, as the result of reduced physical activity. Moreover, focal deletion of ERa from the MeA recapitulated these alterations in energy homeostasis. Conversely, overexpression of ERa in the MeA partially prevented mice from diet-induced obesity, while chemogenetic activation of SIM1-expressing neurons in the MeA transiently promoted physical activity. The results of this study provide important insight into the regions of the brain that mediate ER alpha-dependent energy homeostasis.
C1 NIDDKD, Diabet Endocrinol & Obes Branch, NIH, Baltimore, MD USA.
NIDA, NIH, Baltimore, MD USA.
RP Krashes, MJ (reprint author), 10 Ctr Dr,Bldg 10,Rm 6-3932, Bethesda, MD 20892 USA.
EM michael.krashes@nih.gov
FU Intramural NIH HHS
NR 26
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
EI 1558-8238
J9 J CLIN INVEST
JI J. Clin. Invest.
PD JUL
PY 2015
VL 125
IS 7
BP 2576
EP 2578
DI 10.1172/JCI82578
PG 3
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA CM3AK
UT WOS:000357553300008
PM 26098209
ER
PT J
AU Ou, JX
Vijayasarathy, C
Ziccardi, L
Chen, S
Zeng, Y
Marangoni, D
Pope, JG
Bush, RA
Wu, ZJ
Li, W
Sieving, PA
AF Ou, Jingxing
Vijayasarathy, Camasamudram
Ziccardi, Lucia
Chen, Shan
Zeng, Yong
Marangoni, Dario
Pope, Jodie G.
Bush, Ronald A.
Wu, Zhijian
Li, Wei
Sieving, Paul A.
TI Synaptic pathology and therapeutic repair in adult retinoschisis mouse
by AAV-RS1 transfer
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID X-LINKED RETINOSCHISIS; ON-BIPOLAR CELLS; B-WAVE MUTANTS; JUVENILE
RETINOSCHISIS; LIGHT RESPONSE; GENE-THERAPY; TOPICAL DORZOLAMIDE;
FUNCTIONAL ABNORMALITIES; EXTRACELLULAR-MATRIX; PROTEIN
AB Strategies aimed at invoking synaptic plasticity have therapeutic potential for several neurological conditions. The human retinal synaptic disease X-linked retinoschisis (XLRS) is characterized by impaired visual signal transmission through the retina and progressive visual acuity loss, and mice lacking retinoschisin (RS1) recapitulate human disease. Here, we demonstrate that restoration of RS1 via retina-specific delivery of adeno-associated virus type 8-RS1(AAV8-RS1) vector rescues molecular pathology at the photoreceptor-depolarizing bipolar cell (photoreceptor-DBC) synapse and restores function in adult Rs1-K0 animals. Initial development of the photoreceptor-DBC synapse was normal in the Rs1-K0 retina; however, the metabotropic glutamate receptor 6/transient receptor potential melastatin subfamily M member 1-signaling (mGluR6/TRPM1-signaling) cascade was not properly maintained. Specifically, the TRPM1 channel and G proteins G alpha o, G beta 5, and RGS11 were progressively lost from postsynaptic DBC dendritic tips, whereas the mGluR6 receptor and RGS7 maintained proper synaptic position. This postsynaptic disruption differed from other murine night-blindness models with an electronegative electroretinogram response, which is also characteristic of murine and human XLRS disease. Upon AAV8-RS1 gene transfer to the retina of adult XLRS mice, TRPM1 and the signaling molecules returned to their proper dendritic tip location, and the DBC resting membrane potential was restored. These findings provide insight into the molecular plasticity of a critical synapse in the visual system and demonstrate potential therapeutic avenues for some diseases involving synaptic pathology.
C1 [Ou, Jingxing; Chen, Shan; Pope, Jodie G.; Li, Wei] NEI, Retinal Neurobiol Sect, NIH, Bethesda, MD 20892 USA.
[Vijayasarathy, Camasamudram; Ziccardi, Lucia; Zeng, Yong; Marangoni, Dario; Bush, Ronald A.; Sieving, Paul A.] NIDCD, Sect Translat Res Retinal & Macular Degenerat, NIH, Bethesda, MD USA.
[Wu, Zhijian] NEI, Ocular Gene Therapy Core, NIH, Bethesda, MD 20892 USA.
[Sieving, Paul A.] NEI, NIH, Bethesda, MD 20892 USA.
RP Sieving, PA (reprint author), NEI, 31 Ctr Dr, Bethesda, MD 20892 USA.
EM pas@nei.nih.gov
FU Intramural Research Program of the NIH; National Institute on Deafness
and Other Communication Disorders; National Eye Institute
FX We thank Jinbo Li, Maria Santos, and Suja Hiriyanna for technical
assistance. We also thank the following for providing us with the
antibodies used in this research: Takahisha Furukawa, the Osaka
Bioscience Institute, Osaka, Japan (TRPM1); Catherine W. Morgans, Oregon
Health & Science University, Portland, Oregon, USA (mGluR6); Theodore G.
Wensel, Baylor College of Medicine, Houston, Texas, USA (G beta 5, RGS5,
RGS7); K.A. Martemyanov, The Scripps Research Institute, Jupiter,
Florida, USA (TRPM1); and Amy Lee, University of Iowa, Iowa City, Iowa,
USA (CaV1.4). This work was supported by the Intramural Research Program
of the NIH, the National Institute on Deafness and Other Communication
Disorders, and the National Eye Institute.
NR 60
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U1 1
U2 6
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
EI 1558-8238
J9 J CLIN INVEST
JI J. Clin. Invest.
PD JUL
PY 2015
VL 125
IS 7
BP 2891
EP 2903
DI 10.1172/JCI81380
PG 13
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA CM3AK
UT WOS:000357553300033
PM 26098217
ER
EF