FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Swindle, EJ
Blume, C
Collins, P
Metcalfe, DD
Holgate, ST
Davies, DE
AF Swindle, Emily J.
Blume, Cornelia
Collins, Peter
Metcalfe, Dean D.
Holgate, Stephen T.
Davies, Donna E.
TI Mast cells support rhinovirus but not respiratory syncytial virus
replication and contribute to the pro-inflammatory response to
rhinovirus
SO EUROPEAN RESPIRATORY JOURNAL
LA English
DT Meeting Abstract
C1 [Swindle, Emily J.; Blume, Cornelia; Holgate, Stephen T.; Davies, Donna E.] Univ Southampton, Acad Unit Clin & Expt Sci, Southampton, Hants, England.
[Collins, Peter; Metcalfe, Dean D.] NIAID, NIH, Bethesda, MD 20892 USA.
EM e.j.swindle@soton.ac.uk
RI Davies, Donna/H-2993-2012
NR 0
TC 0
Z9 0
U1 0
U2 0
PU EUROPEAN RESPIRATORY SOC JOURNALS LTD
PI SHEFFIELD
PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND
SN 0903-1936
EI 1399-3003
J9 EUR RESPIR J
JI Eur. Resp. J.
PD SEP 1
PY 2013
VL 42
SU 57
MA 6014
PG 1
WC Respiratory System
SC Respiratory System
GA V38VH
UT WOS:000209370404867
ER
PT J
AU Swindle, EJ
Blume, C
Collins, P
Metcalfe, DD
Holgate, ST
Davies, DE
AF Swindle, Emily J.
Blume, Cornelia
Collins, Peter
Metcalfe, Dean D.
Holgate, Stephen T.
Davies, Donna E.
TI LSC 2013 abstract - Mast cells support rhinovirus but not respiratory
syncytial virus replication and contribute to the pro-inflammatory
response to rhinovirus
SO EUROPEAN RESPIRATORY JOURNAL
LA English
DT Meeting Abstract
C1 [Swindle, Emily J.; Blume, Cornelia; Holgate, Stephen T.; Davies, Donna E.] Univ Southampton, Acad Unit Clin & Expt Sci, Southampton, Hants, England.
[Collins, Peter; Metcalfe, Dean D.] NIAID, NIH, Bethesda, MD 20892 USA.
EM e.j.swindle@soton.ac.uk
RI Davies, Donna/H-2993-2012
NR 0
TC 0
Z9 0
U1 0
U2 0
PU EUROPEAN RESPIRATORY SOC JOURNALS LTD
PI SHEFFIELD
PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND
SN 0903-1936
EI 1399-3003
J9 EUR RESPIR J
JI Eur. Resp. J.
PD SEP 1
PY 2013
VL 42
SU 57
MA 6014
PG 1
WC Respiratory System
SC Respiratory System
GA V38VH
UT WOS:000209370400127
ER
PT J
AU Banks, NK
Brown, L
Hughes, J
Solomon, B
Muenke, M
Page, DC
AF Banks, N. K.
Brown, L.
Hughes, J.
Solomon, B.
Muenke, M.
Page, D. C.
TI PHENOTYPIC DIVERSITY AMONGST PATIENTS WITH AN ISODICENTRIC Y CHROMOSOME.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT International-Federation-of-Fertility-Societies 21st World Congress on
Fertility and Sterility / 69th Annual Meeting of the
American-Society-for-Reproductive-Medicine
CY OCT 12-17, 2013
CL Boston, MA
SP Int Federat Fertil Soc, Amer Soc Reprod Med
C1 [Banks, N. K.; Solomon, B.; Muenke, M.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Brown, L.; Hughes, J.; Page, D. C.] Howard Hughes Med Inst, Whitehead Inst, Cambridge, MA USA.
[Brown, L.; Hughes, J.; Page, D. C.] MIT, Dept Biol, Cambridge, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2013
VL 100
IS 3
SU S
MA P-1027
BP S445
EP S445
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AQ1PY
UT WOS:000342554502040
ER
PT J
AU Banks, NK
Johnston, JJ
Gonsalves, SG
Biesecker, LG
AF Banks, N. K.
Johnston, J. J.
Gonsalves, S. G.
Biesecker, L. G.
TI PREVALENCE AND REPRODUCTIVE PHENOTYPE OF USP9Y MUTATIONS IN AN
UNSELECTED POPULATION.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT International-Federation-of-Fertility-Societies 21st World Congress on
Fertility and Sterility / 69th Annual Meeting of the
American-Society-for-Reproductive-Medicine
CY OCT 12-17, 2013
CL Boston, MA
SP Int Federat Fertil Soc, Amer Soc Reprod Med
C1 [Banks, N. K.; Johnston, J. J.; Gonsalves, S. G.; Biesecker, L. G.] NHGRI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 SEP
PY 2013
VL 100
IS 3
SU S
MA P-1009
BP S439
EP S439
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AQ1PY
UT WOS:000342554502022
ER
PT J
AU Banks, NK
Norian, JM
Henne, MB
AF Banks, N. K.
Norian, J. M.
Henne, M. B.
TI THE STATE OF INSURANCE MANDATES AND INTRACYTOPLASMIC SPERM INJECTION
(ICSI) USE IN THE UNITED STATES
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT International-Federation-of-Fertility-Societies 21st World Congress on
Fertility and Sterility / 69th Annual Meeting of the
American-Society-for-Reproductive-Medicine
CY OCT 12-17, 2013
CL Boston, MA
SP Int Federat Fertil Soc, Amer Soc Reprod Med
C1 [Banks, N. K.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Norian, J. M.] HRC Fertil, Pasadena, CA USA.
[Henne, M. B.] Dept Def Pharmacoecon Ctr, Ft Sam Houston, TX USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2013
VL 100
IS 3
SU S
MA O-296
BP S90
EP S91
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AQ1PY
UT WOS:000342554500294
ER
PT J
AU Banks, NK
Norian, JM
Henne, MB
AF Banks, N. K.
Norian, J. M.
Henne, M. B.
TI CLINIC VOLUME AND INTRACYTOPLASMIC SPERM INJECTION (ICSI) USE IN THE
UNITED STATES.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT International-Federation-of-Fertility-Societies 21st World Congress on
Fertility and Sterility / 69th Annual Meeting of the
American-Society-for-Reproductive-Medicine
CY OCT 12-17, 2013
CL Boston, MA
SP Int Federat Fertil Soc, Amer Soc Reprod Med
C1 [Banks, N. K.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Norian, J. M.] HRC Fertil, Pasadena, CA USA.
[Henne, M. B.] Dept Def Pharmacoecon Ctr, Ft Sam Houston, TX USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2013
VL 100
IS 3
SU S
MA O-145
BP S43
EP S44
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AQ1PY
UT WOS:000342554500145
ER
PT J
AU Bolnick, JM
Zhou, Y
Kilburn, BA
Fisher, SJ
Armant, DR
AF Bolnick, J. M.
Zhou, Y.
Kilburn, B. A.
Fisher, S. J.
Armant, D. R.
TI HBEGF CAN INDUCE CELL INVASION AND PROMOTE SURVIVAL OF FIRST TRIMESTER
TROPHOBLAST.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT International-Federation-of-Fertility-Societies 21st World Congress on
Fertility and Sterility / 69th Annual Meeting of the
American-Society-for-Reproductive-Medicine
CY OCT 12-17, 2013
CL Boston, MA
SP Int Federat Fertil Soc, Amer Soc Reprod Med
C1 [Bolnick, J. M.; Kilburn, B. A.; Armant, D. R.] Wayne State Univ, Detroit, MI USA.
[Zhou, Y.; Fisher, S. J.] UCSF, San Francisco, CA USA.
[Armant, D. R.] NICHD, PRAE, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2013
VL 100
IS 3
SU S
MA P-513
BP S297
EP S297
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AQ1PY
UT WOS:000342554501292
ER
PT J
AU Bolnick, JM
Kilburn, BA
Singh, M
Diamond, MP
Awonuga, A
Armant, DR
AF Bolnick, J. M.
Kilburn, B. A.
Singh, M.
Diamond, M. P.
Awonuga, A.
Armant, D. R.
TI SILDENAFIL STIMULATES EXTRAVILLOUS TROPHOBLAST DIFFERENTIATION THROUGH
CGMP DOWNSTREAM SIGNALING
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT International-Federation-of-Fertility-Societies 21st World Congress on
Fertility and Sterility / 69th Annual Meeting of the
American-Society-for-Reproductive-Medicine
CY OCT 12-17, 2013
CL Boston, MA
SP Int Federat Fertil Soc, Amer Soc Reprod Med
C1 [Bolnick, J. M.; Kilburn, B. A.; Singh, M.; Awonuga, A.; Armant, D. R.] Wayne State Univ, Detroit, MI USA.
[Diamond, M. P.] Georgia Regents Univ, Athens, GA USA.
[Armant, D. R.] NICHD, PRAE, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2013
VL 100
IS 3
SU S
MA O-252
BP S77
EP S77
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AQ1PY
UT WOS:000342554500252
ER
PT J
AU Bolnick, JM
Kilburn, BA
Singh, M
Diamond, MP
Hertz, M
Armant, DR
AF Bolnick, J. M.
Kilburn, B. A.
Singh, M.
Diamond, M. P.
Hertz, M.
Armant, D. R.
TI SILDENAFIL PREVENTS APOPTOSIS OF FIRST TRIMESTER TROPHOBLAST CELLS
EXPOSED TO ENVIRONMENTAL STRESS.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT International-Federation-of-Fertility-Societies 21st World Congress on
Fertility and Sterility / 69th Annual Meeting of the
American-Society-for-Reproductive-Medicine
CY OCT 12-17, 2013
CL Boston, MA
SP Int Federat Fertil Soc, Amer Soc Reprod Med
C1 [Bolnick, J. M.; Kilburn, B. A.; Singh, M.; Hertz, M.; Armant, D. R.] Wayne State Univ, Detroit, MI USA.
[Diamond, M. P.] Georgia Regents Univ, Athens, GA USA.
[Armant, D. R.] NICHD, PRAE, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2013
VL 100
IS 3
SU S
MA O-169
BP S51
EP S51
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AQ1PY
UT WOS:000342554500169
ER
PT J
AU Cooper, JC
Wolff, EF
Levy, G
Levens, ED
DeCherney, AH
Hill, MJ
AF Cooper, J. C.
Wolff, E. F.
Levy, G.
Levens, E. D.
DeCherney, A. H.
Hill, M. J.
TI METHOTREXATE (MTX) TREATMENT FOR ECTOPIC PREGNANCY (EP) AND PREGNANCY OF
UNKNOWN LOCATION (PUL): IS THERE AN ADVERSE EFFECT ON OVARIAN RESERVE?
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT International-Federation-of-Fertility-Societies 21st World Congress on
Fertility and Sterility / 69th Annual Meeting of the
American-Society-for-Reproductive-Medicine
CY OCT 12-17, 2013
CL Boston, MA
SP Int Federat Fertil Soc, Amer Soc Reprod Med
C1 [Wolff, E. F.; Levy, G.; DeCherney, A. H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Levens, E. D.; Hill, M. J.] Shady Grove Fertil Reprod Sci Ctr, Rockville, MD USA.
[Cooper, J. C.] Washington Hosp Ctr, Washington, DC 20010 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 SEP
PY 2013
VL 100
IS 3
SU S
MA P-41
BP S160
EP S160
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AQ1PY
UT WOS:000342554500522
ER
PT J
AU Cox, J
Heitmann, R
Hailstorks, T
Armstrong, A
AF Cox, J.
Heitmann, R.
Hailstorks, T.
Armstrong, A.
TI MRI EVIDENCE OF EMBRYO IMPLANTATION ONTO THE FIBROMUSCULAR UTERINE
SEPTUM.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT International-Federation-of-Fertility-Societies 21st World Congress on
Fertility and Sterility / 69th Annual Meeting of the
American-Society-for-Reproductive-Medicine
CY OCT 12-17, 2013
CL Boston, MA
SP Int Federat Fertil Soc, Amer Soc Reprod Med
C1 [Cox, J.; Heitmann, R.; Hailstorks, T.; Armstrong, A.] NICHD, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2013
VL 100
IS 3
SU S
MA P-810
BP S382
EP S382
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AQ1PY
UT WOS:000342554501584
ER
PT J
AU Devine, K
Driggers, PH
Chu, TJ
DeCherney, AH
Segars, JH
AF Devine, K.
Driggers, P. H.
Chu, T. J.
DeCherney, A. H.
Segars, J. H.
TI TISSUE-SPECIFIC KNOCKOUT OFA-KINASE ANCHORING PROTEIN 13 (AKAP13) - A
POTENTIAL MURINE MODEL FOR POLYCYSTIC OVARIAN SYNDROME.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT International-Federation-of-Fertility-Societies 21st World Congress on
Fertility and Sterility / 69th Annual Meeting of the
American-Society-for-Reproductive-Medicine
CY OCT 12-17, 2013
CL Boston, MA
SP Int Federat Fertil Soc, Amer Soc Reprod Med
C1 [Devine, K.; Driggers, P. H.; Chu, T. J.; DeCherney, A. H.; Segars, J. H.] Eunice Kennedy Shriver Inst Child Hlth & Human De, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
NR 0
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 SEP
PY 2013
VL 100
IS 3
SU S
MA O-202
BP S61
EP S62
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AQ1PY
UT WOS:000342554500202
ER
PT J
AU Devine, K
Richter, KS
Levens, ED
DeCherney, AH
Stillman, R
Widra, EA
AF Devine, K.
Richter, K. S.
Levens, E. D.
DeCherney, A. H.
Stillman, R.
Widra, E. A.
TI SINGLE THAWED BLASTOCYST TRANSFER MAXIMIZES LIVEBORN CHILDREN PER EMBRYO
WHILE MINIMIZING PRETERM BIRTH: ANALYSIS OF 1691 FROZEN BLASTOCYST
TRANSFERS (FBT)
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT International-Federation-of-Fertility-Societies 21st World Congress on
Fertility and Sterility / 69th Annual Meeting of the
American-Society-for-Reproductive-Medicine
CY OCT 12-17, 2013
CL Boston, MA
SP Int Federat Fertil Soc, Amer Soc Reprod Med
C1 [Richter, K. S.; Levens, E. D.; Stillman, R.; Widra, E. A.] Shady Grove Fertil Reprod Sci Ctr, Rockville, MD USA.
[Devine, K.; DeCherney, A. H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2013
VL 100
IS 3
SU S
MA O-46
BP S15
EP S15
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AQ1PY
UT WOS:000342554500047
ER
PT J
AU Eisenberg, ML
Kime, SD
Chen, Z
Sundaram, R
Schisterman, EF
Louis, GMB
AF Eisenberg, M. L.
Kime, S. D.
Chen, Z.
Sundaram, R.
Schisterman, E. F.
Louis, G. M. Buck
TI THE RELATIONSHIP BETWEEN MALE BODY MASS INDEX, ADIPOSITY, AND ACTIVITY
LEVEL ON SEMEN QUALITY: DATA FROM THE LIFE STUDY.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT International-Federation-of-Fertility-Societies 21st World Congress on
Fertility and Sterility / 69th Annual Meeting of the
American-Society-for-Reproductive-Medicine
CY OCT 12-17, 2013
CL Boston, MA
SP Int Federat Fertil Soc, Amer Soc Reprod Med
C1 [Eisenberg, M. L.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Kime, S. D.; Chen, Z.; Sundaram, R.; Schisterman, E. F.; Louis, G. M. Buck] NICHHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2013
VL 100
IS 3
SU S
MA O-408
BP S124
EP S124
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AQ1PY
UT WOS:000342554500405
ER
PT J
AU Eltoukhi, HM
Hill, MJ
Zarek, SM
DeCherney, AH
Richter, KS
Wolff, EE
AF Eltoukhi, H. M.
Hill, M. J.
Zarek, S. M.
DeCherney, A. H.
Richter, K. S.
Wolff, E. F.
TI RELATIONSHIP BETWEEN ENDOMETRIAL THICKNESS AND ASSISTED REPRODUCTIVE
TECHNOLOGY (ART) OUTCOMES IN ENDOMETRIOSIS PATIENTS.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT International-Federation-of-Fertility-Societies 21st World Congress on
Fertility and Sterility / 69th Annual Meeting of the
American-Society-for-Reproductive-Medicine
CY OCT 12-17, 2013
CL Boston, MA
SP Int Federat Fertil Soc, Amer Soc Reprod Med
C1 [Eltoukhi, H. M.; Hill, M. J.; Zarek, S. M.; DeCherney, A. H.; Wolff, E. F.] NICHHD, Program Reprod & Adult Endocrinol, Eunice Kennedy Shriver, NIH, Bethesda, MD 20892 USA.
[Richter, K. S.] Shady Grove Fertil Reprod Sci Ctr, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 SEP
PY 2013
VL 100
IS 3
SU S
MA P-830
BP S387
EP S387
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AQ1PY
UT WOS:000342554501603
ER
PT J
AU Fru, KN
Hill, MJ
Bertone-Johnson, ER
DeCherney, AH
Levens, ED
Whitcomb, BW
AF Fru, K. N.
Hill, M. J.
Bertone-Johnson, E. R.
DeCherney, A. H.
Levens, E. D.
Whitcomb, B. W.
TI OOCYTE DONOR ANTI-MULLERIAN HORMONE (AMH) AND ANTRAL FOLLICLE COUNT
(AFC) PREDICT DONOR OOCYTE YIELD AND RECIPIENT IMPLANTATION.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT International-Federation-of-Fertility-Societies 21st World Congress on
Fertility and Sterility / 69th Annual Meeting of the
American-Society-for-Reproductive-Medicine
CY OCT 12-17, 2013
CL Boston, MA
SP Int Federat Fertil Soc, Amer Soc Reprod Med
C1 [Fru, K. N.; Hill, M. J.; DeCherney, A. H.] Eunice Kennedy Shriver Natl Inst Child & Human De, Reprod Endocrinol & Infertil Program Reprod & Adu, NIH, Bethesda, MD USA.
[Bertone-Johnson, E. R.; Whitcomb, B. W.] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Div Biostat & Epidemiol, Amherst, MA 01003 USA.
[Levens, E. D.] Shady Grove Fertil Resprod Sci Ctr, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2013
VL 100
IS 3
SU S
MA O-461
BP S140
EP S140
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AQ1PY
UT WOS:000342554500457
ER
PT J
AU Fru, KN
Hill, MJ
Bertone-Johnson, ER
DeCherney, AH
Whitcomb, BW
Levens, ED
AF Fru, K. N.
Hill, M. J.
Bertone-Johnson, E. R.
DeCherney, A. H.
Whitcomb, B. W.
Levens, E. D.
TI TOTAL NUMBER OF OOCYTES RETRIEVED BUT NOT FOLLICLE STIMULATING HORMONE
(FSH) DOSE VARIES ACROSS MULTIPLE CYCLES IN REPEAT OOCYTE DONORS.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT International-Federation-of-Fertility-Societies 21st World Congress on
Fertility and Sterility / 69th Annual Meeting of the
American-Society-for-Reproductive-Medicine
CY OCT 12-17, 2013
CL Boston, MA
SP Int Federat Fertil Soc, Amer Soc Reprod Med
C1 [Fru, K. N.; Hill, M. J.; DeCherney, A. H.] Eunice Kennedy Shriver Natl Inst Child & Human De, Reprod Endocrinol & Infertil Program Reprod & Adu, NIH, Bethesda, MD USA.
[Bertone-Johnson, E. R.; Whitcomb, B. W.] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Div Biostat & Epidemiol, Amherst, MA 01003 USA.
[Levens, E. D.] Shady Grove Fertil Resprod Sci Ctr, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2013
VL 100
IS 3
SU S
MA O-170
BP S52
EP S52
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AQ1PY
UT WOS:000342554500170
ER
PT J
AU Heitmann, RJ
Richter, KS
Devine, K
McKeeby, J
DeCherney, AH
Widra, EA
AF Heitmann, R. J.
Richter, K. S.
Devine, K.
McKeeby, J.
DeCherney, A. H.
Widra, E. A.
TI INCREASED LIVE BIRTHS AMONG PATIENTS USING INTAMUSCULAR VERSUS VAGINAL
PROGESTERONE FOR LUTEAL PHASE SUPPORT DURING FROZEN BLASTOCYST TRANSFER.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT International-Federation-of-Fertility-Societies 21st World Congress on
Fertility and Sterility / 69th Annual Meeting of the
American-Society-for-Reproductive-Medicine
CY OCT 12-17, 2013
CL Boston, MA
SP Int Federat Fertil Soc, Amer Soc Reprod Med
C1 [Heitmann, R. J.; Devine, K.; DeCherney, A. H.] NICHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Heitmann, R. J.; Richter, K. S.; Devine, K.; McKeeby, J.; Widra, E. A.] Shady Grove Fertil Reprod Sci Ctr, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2013
VL 100
IS 3
SU S
MA P-1078
BP S459
EP S460
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AQ1PY
UT WOS:000342554502091
ER
PT J
AU Heitmann, RJ
Hill, MJ
James, AN
Csokmay, JM
Segars, JH
Payson, MD
AF Heitmann, R. J.
Hill, M. J.
James, A. N.
Csokmay, J. M.
Segars, J. H.
Payson, M. D.
TI IMPLANTATION AND ONGOING PREGNANCY ARE INCREASED AS A RESULT OF
IMPROVEMENTS IN AIR HANDLING AND LABORATORY ENVIRONMENT.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT International-Federation-of-Fertility-Societies 21st World Congress on
Fertility and Sterility / 69th Annual Meeting of the
American-Society-for-Reproductive-Medicine
CY OCT 12-17, 2013
CL Boston, MA
SP Int Federat Fertil Soc, Amer Soc Reprod Med
C1 [Heitmann, R. J.; Hill, M. J.; Csokmay, J. M.; Segars, J. H.] NICHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Heitmann, R. J.; Hill, M. J.; Csokmay, J. M.; Segars, J. H.; Payson, M. D.] Walter Reed Natl Mil Med Ctr, Div Reprod Endocrinol, Bethesda, MD USA.
[James, A. N.] ART Inst Washington, Bethesda, MD USA.
[Payson, M. D.] Dominion Fertil, Arlington, VA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2013
VL 100
IS 3
SU S
MA O-479
BP S145
EP S146
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AQ1PY
UT WOS:000342554500475
ER
PT J
AU Hill, MJ
Whitcomb, BW
Lewis, TD
Levens, ED
DeCherney, AH
Propst, AM
AF Hill, M. J.
Whitcomb, B. W.
Lewis, T. D.
Levens, E. D.
DeCherney, A. H.
Propst, A. M.
TI PROGESTERONE LUTEAL SUPPORT FOLLOWING OVULATION INDUCTION AND
INTRAUTERINE INSEMINATION CYCLES: A SYSTEMATIC REVIEW AND META-ANALYSIS
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT International-Federation-of-Fertility-Societies 21st World Congress on
Fertility and Sterility / 69th Annual Meeting of the
American-Society-for-Reproductive-Medicine
CY OCT 12-17, 2013
CL Boston, MA
SP Int Federat Fertil Soc, Amer Soc Reprod Med
C1 [Hill, M. J.; Lewis, T. D.; DeCherney, A. H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod Endocrinol & Infertil, Bethesa, MD USA.
[Whitcomb, B. W.] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Div Biostat & Epidemiol, Amherst, MA 01003 USA.
[Levens, E. D.] Shady Grove Fertil Reprod Sci Ctr, Rockville, MD USA.
[Propst, A. M.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2013
VL 100
IS 3
SU S
MA P-529
BP S301
EP S301
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AQ1PY
UT WOS:000342554501308
ER
PT J
AU Hill, MJ
Richter, KS
Zarek, SM
DeCherney, AH
Osheroff, JE
Levens, ED
AF Hill, M. J.
Richter, K. S.
Zarek, S. M.
DeCherney, A. H.
Osheroff, J. E.
Levens, E. D.
TI SINGLE AND DOUBLE DONOR SPERM INTRAUTERINE INSEMINATION CYCLES FOR MALE
FACTOR INFERTILITY: DOES DOUBLE IUI INCREASE CLINICAL PREGNANCY RATES?
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT International-Federation-of-Fertility-Societies 21st World Congress on
Fertility and Sterility / 69th Annual Meeting of the
American-Society-for-Reproductive-Medicine
CY OCT 12-17, 2013
CL Boston, MA
SP Int Federat Fertil Soc, Amer Soc Reprod Med
C1 [Hill, M. J.; Zarek, S. M.; DeCherney, A. H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Richter, K. S.; Osheroff, J. E.; Levens, E. D.] Shady Grove Fertil Reprod Sci Ctr, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
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 SEP
PY 2013
VL 100
IS 3
SU S
MA O-231
BP S71
EP S71
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AQ1PY
UT WOS:000342554500231
ER
PT J
AU Hillman, JK
Butts, SF
Playford, MP
Mehta, NN
Dokras, A
AF Hillman, J. K.
Butts, S. F.
Playford, M. P.
Mehta, N. N.
Dokras, A.
TI ATHEROGENIC LIPOPROTEIN PROFILE AND DECREASED HDL FUNCTION SUPPORT
INCREASED RISK OF CARDIOVASCULAR DISEASE (CVD) IN YOUNG WOMEN WITH
POLYCYSTIC OVARY SYNDROME (PCOS)
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT International-Federation-of-Fertility-Societies 21st World Congress on
Fertility and Sterility / 69th Annual Meeting of the
American-Society-for-Reproductive-Medicine
CY OCT 12-17, 2013
CL Boston, MA
SP Int Federat Fertil Soc, Amer Soc Reprod Med
C1 [Hillman, J. K.; Butts, S. F.; Dokras, A.] Univ Penn, Philadelphia, PA 19104 USA.
[Playford, M. P.; Mehta, N. N.] NHLBI, Sect Inflammat & Cardiometab Dis, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2013
VL 100
IS 3
SU S
MA P-726
BP S358
EP S358
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AQ1PY
UT WOS:000342554501501
ER
PT J
AU Hurliman, A
Casson, P
Ashikaga, T
Brown, S
Bates, GW
AF Hurliman, A.
Casson, P.
Ashikaga, T.
Brown, S.
Bates, G. W.
CA Reprod Med Network
TI INCREASING ANDROGEN RECEPTOR GENE CAG REPEAT ARE ASSOCIATED WITH
IMPROVED RESPONSE TO CLOMIPHENE CITRATE: AN EXPLORATORY SUB-ANALYSIS OF
THE PREGNANCY IN POLYCYSTIC OVARY SYNDROME TRIAL (PPCOS I).
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT International-Federation-of-Fertility-Societies 21st World Congress on
Fertility and Sterility / 69th Annual Meeting of the
American-Society-for-Reproductive-Medicine
CY OCT 12-17, 2013
CL Boston, MA
SP Int Federat Fertil Soc, Amer Soc Reprod Med
C1 [Hurliman, A.; Casson, P.; Ashikaga, T.; Brown, S.] Univ Vermont, Burlington, VT USA.
[Bates, G. W.] Univ Alabama Birmingham, Birmingham, AL USA.
[Reprod Med Network] NICHD, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 SEP
PY 2013
VL 100
IS 3
SU S
MA O-12
BP S4
EP S4
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AQ1PY
UT WOS:000342554500013
ER
PT J
AU Johnstone, E
Dorais, J
Parsons, P
Louis, G
Hammoud, A
Peterson, CM
AF Johnstone, E.
Dorais, J.
Parsons, P.
Louis, G.
Hammoud, A.
Peterson, C. M.
TI INCREASED TRACE METALS IN BLOOD AND URINE ARE ASSOCIATED WITH UTERINE
LEIOMYOMATA.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT International-Federation-of-Fertility-Societies 21st World Congress on
Fertility and Sterility / 69th Annual Meeting of the
American-Society-for-Reproductive-Medicine
CY OCT 12-17, 2013
CL Boston, MA
SP Int Federat Fertil Soc, Amer Soc Reprod Med
C1 [Johnstone, E.; Dorais, J.; Hammoud, A.; Peterson, C. M.] Univ Utah, Salt Lake City, UT USA.
[Louis, G.] NIH, Bethesda, MD 20892 USA.
[Parsons, P.] Univ Albany, Albany, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2013
VL 100
IS 3
SU S
MA P-952
BP S422
EP S423
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AQ1PY
UT WOS:000342554501723
ER
PT J
AU Louis, GMB
Druschel, C
Sundaram, R
Bell, E
Yeung, E
Kus, C
AF Louis, G. M. Buck
Druschel, C.
Sundaram, R.
Bell, E.
Yeung, E.
Kus, C.
TI POPULATION BASED METHODOLOGY FOR ASSESSING INFERTILITY TREATMENT AND
CHILD HEALTH, UPSTATE KIDS STUDY.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT International-Federation-of-Fertility-Societies 21st World Congress on
Fertility and Sterility / 69th Annual Meeting of the
American-Society-for-Reproductive-Medicine
CY OCT 12-17, 2013
CL Boston, MA
SP Int Federat Fertil Soc, Amer Soc Reprod Med
C1 [Louis, G. M. Buck; Sundaram, R.; Yeung, E.] NICHD, Div Epidemiol Stat & Prevent Res, Rockville, MD USA.
[Druschel, C.] NYS Dept Hlth, Congenital Malformat Registry, Albany, NY USA.
[Bell, E.] SUNY Albany, Dept Environm Hlth, Albany, NY 12222 USA.
[Bell, E.] SUNY Albany, Dept Epidemiol, Albany, NY 12222 USA.
[Kus, C.] NYS Dept Hlth, Div Family Hlth, Albany, NY USA.
RI Yeung, Edwina/F-5992-2015
OI Yeung, Edwina/0000-0002-3851-2613
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2013
VL 100
IS 3
SU S
MA P-1186
BP S490
EP S490
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AQ1PY
UT WOS:000342554502196
ER
PT J
AU Louis, GMB
Sundaram, R
Sweeney, A
Schisterman, EF
Kannan, K
AF Louis, G. M. Buck
Sundaram, R.
Sweeney, A.
Schisterman, E. F.
Kannan, K.
TI BISPHENOL A, PHTHALATES AND COUPLE FECUNDITY, THE LIFE STUDY.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT International-Federation-of-Fertility-Societies 21st World Congress on
Fertility and Sterility / 69th Annual Meeting of the
American-Society-for-Reproductive-Medicine
CY OCT 12-17, 2013
CL Boston, MA
SP Int Federat Fertil Soc, Amer Soc Reprod Med
C1 [Louis, G. M. Buck; Sundaram, R.; Schisterman, E. F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Rockville, MD USA.
[Sweeney, A.] Texas A&M Rural Sch Publ Hlth, College Stn, TX USA.
[Kannan, K.] NYS Dept Hlth, Wadsworth Ctr, Albany, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
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 SEP
PY 2013
VL 100
IS 3
SU S
MA O-2
BP S1
EP S1
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AQ1PY
UT WOS:000342554500003
ER
PT J
AU Malik, M
Deng, J
Britten, J
Levy, G
Segars, J
Catherino, WH
AF Malik, M.
Deng, J.
Britten, J.
Levy, G.
Segars, J.
Catherino, W. H.
TI ESTROGEN AND PROGESTERONE STIMULATE EXTRACELLULAR MATRIX PRODUCTION IN
MYOMETRIUM AND LEIOMYOMA 3-DIMENSIONAL CULTURES.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT International-Federation-of-Fertility-Societies 21st World Congress on
Fertility and Sterility / 69th Annual Meeting of the
American-Society-for-Reproductive-Medicine
CY OCT 12-17, 2013
CL Boston, MA
SP Int Federat Fertil Soc, Amer Soc Reprod Med
C1 [Malik, M.; Deng, J.; Britten, J.; Levy, G.; Segars, J.; Catherino, W. H.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
[Levy, G.; Segars, J.; Catherino, W. H.] Eunice Kennedy Shriver NICHD, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
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 SEP
PY 2013
VL 100
IS 3
SU S
MA P-880
BP S401
EP S401
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AQ1PY
UT WOS:000342554501652
ER
PT J
AU Malik, M
Britten, J
Deng, J
Segars, J
Catherino, WH
AF Malik, M.
Britten, J.
Deng, J.
Segars, J.
Catherino, W. H.
TI PREVENTING MISLEADING RESULTS PRIOR TO CLINICAL TRIALS: EXTRACELLULAR
MATRIX IN 3-DIMENSIONAL LEIOMYOMA CULTURES WAS MAINTAINED DESPITE
TREATMENT WITH THE ROCK INHIBITOR FASUDIL.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT International-Federation-of-Fertility-Societies 21st World Congress on
Fertility and Sterility / 69th Annual Meeting of the
American-Society-for-Reproductive-Medicine
CY OCT 12-17, 2013
CL Boston, MA
SP Int Federat Fertil Soc, Amer Soc Reprod Med
C1 [Malik, M.; Britten, J.; Deng, J.; Segars, J.; Catherino, W. H.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
[Segars, J.; Catherino, W. H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 SEP
PY 2013
VL 100
IS 3
SU S
MA P-881
BP S401
EP S402
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AQ1PY
UT WOS:000342554501653
ER
PT J
AU Mumford, SL
Sundaram, R
Schisterman, EF
Barr, DB
Sweeney, AM
Louis, GMB
AF Mumford, S. L.
Sundaram, R.
Schisterman, E. F.
Barr, D. Boyd
Sweeney, A. M.
Louis, G. M. Buck
TI URINARY LIGNAN CONCENTRATIONS AND COUPLE FECUNDITY: THE LIFE STUDY
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT International-Federation-of-Fertility-Societies 21st World Congress on
Fertility and Sterility / 69th Annual Meeting of the
American-Society-for-Reproductive-Medicine
CY OCT 12-17, 2013
CL Boston, MA
SP Int Federat Fertil Soc, Amer Soc Reprod Med
C1 [Mumford, S. L.; Sundaram, R.; Schisterman, E. F.; Louis, G. M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Rockville, MD USA.
[Barr, D. Boyd] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.
[Sweeney, A. M.] Texas A&M Hlth Sci Ctr, Sch Rural Publ Hlth, College Stn, TX USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2013
VL 100
IS 3
SU S
MA O-265
BP S81
EP S81
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AQ1PY
UT WOS:000342554500264
ER
PT J
AU Muneyyirci-Delale, O
Charles, C
Sinaii, N
Anopa, J
Dalloul, M
Stratton, P
AF Muneyyirci-Delale, O.
Charles, C.
Sinaii, N.
Anopa, J.
Dalloul, M.
Stratton, P.
TI CHANGES IN BONE DENSITY IN WOMEN WITH ENDOMETRIOSIS ON LEUPROLIDE VS
NORETHINDRONE TREATMENT
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT International-Federation-of-Fertility-Societies 21st World Congress on
Fertility and Sterility / 69th Annual Meeting of the
American-Society-for-Reproductive-Medicine
CY OCT 12-17, 2013
CL Boston, MA
SP Int Federat Fertil Soc, Amer Soc Reprod Med
C1 [Muneyyirci-Delale, O.; Charles, C.; Anopa, J.; Dalloul, M.] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA.
[Muneyyirci-Delale, O.] Kings Cty Hosp Ctr, Brooklyn, NY USA.
[Sinaii, N.] NIH, Biostat & Clin Epidemiol Serv, Ctr Clin, Bethesda, MD 20892 USA.
[Stratton, P.] NICHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 SEP
PY 2013
VL 100
IS 3
SU S
MA O-335
BP S102
EP S103
PG 3
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AQ1PY
UT WOS:000342554500333
ER
PT J
AU Schisterman, EF
Browne, RW
Barr, DB
Chen, Z
Mumford, SL
Louis, GMB
AF Schisterman, E. F.
Browne, R. W.
Barr, D. Boyd
Chen, Z.
Mumford, S. L.
Louis, G. M. Buck
TI LIPID LEVELS AND COUPLE FECUNDITY: THE LIFE STUDY
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT International-Federation-of-Fertility-Societies 21st World Congress on
Fertility and Sterility / 69th Annual Meeting of the
American-Society-for-Reproductive-Medicine
CY OCT 12-17, 2013
CL Boston, MA
SP Int Federat Fertil Soc, Amer Soc Reprod Med
C1 [Schisterman, E. F.; Chen, Z.; Mumford, S. L.; Louis, G. M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Rockville, MD USA.
[Browne, R. W.] SUNY Buffalo, Dept Biotech & Clin Lab Sci, Buffalo, NY 14260 USA.
[Barr, D. Boyd] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 SEP
PY 2013
VL 100
IS 3
SU S
MA P-667
BP S341
EP S341
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AQ1PY
UT WOS:000342554501444
ER
PT J
AU Schisterman, EF
Silver, RM
Mumford, SL
Galai, N
Wactawski-Wende, J
Stanford, JB
AF Schisterman, E. F.
Silver, R. M.
Mumford, S. L.
Galai, N.
Wactawski-Wende, J.
Stanford, J. B.
TI RANDOMIZED CLINICAL TRIAL OF PRECONCEPTION LOW DOSE ASPIRIN USE AND
TIME-TO-PREGNANCY: THE EAGER TRIAL.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT International-Federation-of-Fertility-Societies 21st World Congress on
Fertility and Sterility / 69th Annual Meeting of the
American-Society-for-Reproductive-Medicine
CY OCT 12-17, 2013
CL Boston, MA
SP Int Federat Fertil Soc, Amer Soc Reprod Med
C1 [Schisterman, E. F.; Mumford, S. L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Rockville, MD USA.
[Silver, R. M.; Stanford, J. B.] Univ Utah, Salt Lake City, UT USA.
[Galai, N.] Univ Haifa, IL-31999 Haifa, Israel.
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 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2013
VL 100
IS 3
SU S
MA O-327
BP S100
EP S100
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AQ1PY
UT WOS:000342554500325
ER
PT J
AU Schliep, KC
Mumford, SL
Chen, Z
Sharp, HT
Peterson, CM
Louis, GMB
AF Schliep, K. C.
Mumford, S. L.
Chen, Z.
Sharp, H. T.
Peterson, C. M.
Louis, G. M. Buck
TI RELATING PELVIC PAIN TYPOLOGY AND LOCATION TO ENDOMETRIOSIS DIAGNOSIS
AMONG BOTH WOMEN SEEKING AND NOT SEEKING CLINICAL CARE.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT International-Federation-of-Fertility-Societies 21st World Congress on
Fertility and Sterility / 69th Annual Meeting of the
American-Society-for-Reproductive-Medicine
CY OCT 12-17, 2013
CL Boston, MA
SP Int Federat Fertil Soc, Amer Soc Reprod Med
C1 [Schliep, K. C.; Mumford, S. L.; Chen, Z.; Louis, G. M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Rockville, MD USA.
[Sharp, H. T.; Peterson, C. M.] Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2013
VL 100
IS 3
SU S
MA P-754
BP S366
EP S366
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AQ1PY
UT WOS:000342554501529
ER
PT J
AU Sharan, C
Halder, S
Nair, S
Segars, J
Al-Hendy, A
AF Sharan, C.
Halder, S.
Nair, S.
Segars, J.
Al-Hendy, A.
TI PARICALCITOL, VITAMIN D3 RECEPTOR AGONIST IS SUPERIOR TO VITAMIN D3 IN
REDUCING PROLIFERATION OF HUMAN UTERINE LEIOMYOMA CELLS.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT International-Federation-of-Fertility-Societies 21st World Congress on
Fertility and Sterility / 69th Annual Meeting of the
American-Society-for-Reproductive-Medicine
CY OCT 12-17, 2013
CL Boston, MA
SP Int Federat Fertil Soc, Amer Soc Reprod Med
C1 [Sharan, C.; Halder, S.; Nair, S.; Al-Hendy, A.] Meharry Med Coll, CWHR, Nashville, TN 37208 USA.
[Segars, J.] NICHD, Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2013
VL 100
IS 3
SU S
MA P-882
BP S402
EP S402
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AQ1PY
UT WOS:000342554501654
ER
PT J
AU Stratton, P
Sinaii, N
Khachikyan, I
Ortiz, R
Gemmill, J
Shah, J
AF Stratton, P.
Sinaii, N.
Khachikyan, I.
Ortiz, R.
Gemmill, J.
Shah, J.
TI INTERRELATIONSHIP AMONG LEVATOR SPASM, SENSITIZATION, MYOFASCIAL
DYSFUNCTION, ANXIETY AND DEPRESSION IN PATIENTS WITH ENDOMETRIOSIS AND
CHRONIC PELVIC PAIN
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT International-Federation-of-Fertility-Societies 21st World Congress on
Fertility and Sterility / 69th Annual Meeting of the
American-Society-for-Reproductive-Medicine
CY OCT 12-17, 2013
CL Boston, MA
SP Int Federat Fertil Soc, Amer Soc Reprod Med
C1 [Stratton, P.; Khachikyan, I.; Gemmill, J.] NICHD, PRAE, Bethesda, MD USA.
[Sinaii, N.] CC, BCES, Bethesda, MD USA.
[Ortiz, R.; Shah, J.] CC, RM, Bethesda, MD USA.
[Ortiz, R.] Loyola SOM, Maywood, IL USA.
[Gemmill, J.] NYCOM, Old Westbury, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2013
VL 100
IS 3
SU S
MA O-67
BP S21
EP S21
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AQ1PY
UT WOS:000342554500068
ER
PT J
AU Trussell, JC
Christman, GM
Ohl, DA
Krawetz, SA
Snyder, PJ
AF Trussell, J. C.
Christman, G. M.
Ohl, D. A.
Krawetz, S. A.
Snyder, P. J.
CA Reproductive Med Network
TI NEARLY ALL SURVEYED REPRODUCTIVE UROLOGISTS FEEL A PROSPECTIVE
VARICOCELECTOMY TRIAL IS IMPORTANT AND WORTHWHILE
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT International-Federation-of-Fertility-Societies 21st World Congress on
Fertility and Sterility / 69th Annual Meeting of the
American-Society-for-Reproductive-Medicine
CY OCT 12-17, 2013
CL Boston, MA
SP Int Federat Fertil Soc, Amer Soc Reprod Med
C1 [Trussell, J. C.] Upstate Univ Hosp, Syracuse, NY USA.
[Christman, G. M.] Univ Florida, Gainesville, FL USA.
[Ohl, D. A.] Univ Michigan, Ctr Hlth, Ann Arbor, MI 48109 USA.
[Krawetz, S. A.] Wayne State Univ, Detroit, MI USA.
[Snyder, P. J.] Hosp Univ Penn, Philadelphia, PA 19104 USA.
[Reproductive Med Network] Kennedy Shriver Natl Inst Child Hlth & Human Dev, NICHD, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2013
VL 100
IS 3
SU S
MA O-97
BP S30
EP S30
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AQ1PY
UT WOS:000342554500098
ER
PT J
AU Wolff, EF
Libfraind, LL
Weitzel, RP
Tilly, J
DeCherney, AH
Tisdale, JE
AF Wolff, E. F.
Libfraind, L. L.
Weitzel, R. P.
Tilly, J.
DeCherney, A. H.
Tisdale, J. E.
TI OOGONIAL STEM CELLS GENERATE MATURE OOCYTES IN AN AUTOLOGOUS RHESUS
MACAQUE TRANSPLANTATION MODEL.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT International-Federation-of-Fertility-Societies 21st World Congress on
Fertility and Sterility / 69th Annual Meeting of the
American-Society-for-Reproductive-Medicine
CY OCT 12-17, 2013
CL Boston, MA
SP Int Federat Fertil Soc, Amer Soc Reprod Med
C1 [Wolff, E. F.; Libfraind, L. L.; DeCherney, A. H.] NICHD, Program Reprod & Adult Endocrinol, Bethesda, MD USA.
[Weitzel, R. P.; Tisdale, J. E.] NHLBI, MCHB, Bethesda, MD 20892 USA.
[Tilly, J.] MGH, Vincent Ctr Reprod Biol, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 SEP
PY 2013
VL 100
IS 3
SU S
MA O-133
BP S40
EP S40
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AQ1PY
UT WOS:000342554500133
ER
PT J
AU Yeung, EH
Robledo, C
Boghossian, N
Ye, A
Bell, E
Schisterman, E
AF Yeung, E. H.
Robledo, C.
Boghossian, N.
Ye, A.
Bell, E.
Schisterman, E.
TI MODELING THE CAUSAL EFFECT OF ASSISTED REPRODUCTIVE TECHNOLOGY (ART) ON
NEURODEVELOPMENTAL IMPAIRMENT
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT International-Federation-of-Fertility-Societies 21st World Congress on
Fertility and Sterility / 69th Annual Meeting of the
American-Society-for-Reproductive-Medicine
CY OCT 12-17, 2013
CL Boston, MA
SP Int Federat Fertil Soc, Amer Soc Reprod Med
C1 [Yeung, E. H.; Robledo, C.; Boghossian, N.; Ye, A.; Schisterman, E.] NICHD, Epidemiol Branch, DESPR, NIH, Bethesda, MD USA.
[Bell, E.] SUNY Albany, Sch Publ Hlth, Dept Environm Hlth Sci, Rensselaer, NY USA.
RI Yeung, Edwina/F-5992-2015
OI Yeung, Edwina/0000-0002-3851-2613
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 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2013
VL 100
IS 3
SU S
MA P-1093
BP S464
EP S464
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AQ1PY
UT WOS:000342554502106
ER
PT J
AU Zarek, SM
Alford, CE
Edwards, KK
Segars, JH
Armstrong, AY
AF Zarek, S. M.
Alford, C. E.
Edwards, K. K.
Segars, J. H.
Armstrong, A. Y.
TI USE OF THE LEVONORGESTREL CONTAINING INTRAUTERINE DEVICE (LNG-IUS) AS A
STRATEGY TO DECREASE MATERNAL MORTALITY IN UGANDA: ESTIMATING IMPACT
WITH A PREDICTION MODEL.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT International-Federation-of-Fertility-Societies 21st World Congress on
Fertility and Sterility / 69th Annual Meeting of the
American-Society-for-Reproductive-Medicine
CY OCT 12-17, 2013
CL Boston, MA
SP Int Federat Fertil Soc, Amer Soc Reprod Med
C1 [Zarek, S. M.; Segars, J. H.; Armstrong, A. Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Alford, C. E.] South Florida Inst Reprod Med, Naples, FL USA.
[Edwards, K. K.] Howard Univ, Dept Obstet & Gynecol, Washington, DC 20059 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2013
VL 100
IS 3
SU S
MA P-584
BP S317
EP S317
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AQ1PY
UT WOS:000342554501362
ER
PT J
AU Zarek, SM
Alford, CE
Mumford, SL
Edwards, KK
Segars, JH
Armstrong, AY
AF Zarek, S. M.
Alford, C. E.
Mumford, S. L.
Edwards, K. K.
Segars, J. H.
Armstrong, A. Y.
TI ESTIMATED REDUCTION OF VERTICAL TRANSMISSION OF HUMAN IMMUNODEFICIENCY
VIRUS (HIV) WITH THE LEVONORGESTREL INTRAUTERINE DEVICE (LNG-IUS): USE
OF A PREDICTION MODEL TO ESTIMATE THE IMPACT OF LNG-IUS.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT International-Federation-of-Fertility-Societies 21st World Congress on
Fertility and Sterility / 69th Annual Meeting of the
American-Society-for-Reproductive-Medicine
CY OCT 12-17, 2013
CL Boston, MA
SP Int Federat Fertil Soc, Amer Soc Reprod Med
C1 [Zarek, S. M.; Segars, J. H.; Armstrong, A. Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Alford, C. E.] South Florida Inst Reprod Med, Naples, FL USA.
[Mumford, S. L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD USA.
[Edwards, K. K.] Howard Univ, Dept Obstet & Gynecol, Washington, DC 20059 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2013
VL 100
IS 3
SU S
MA P-582
BP S316
EP S317
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AQ1PY
UT WOS:000342554501360
ER
PT J
AU Zarek, SM
Hill, MJ
Eltoukhi, HM
DeCherney, AH
Widra, E
Wolff, EF
AF Zarek, S. M.
Hill, M. J.
Eltoukhi, H. M.
DeCherney, A. H.
Widra, E.
Wolff, E. F.
TI THE EFFECT OF PEAK ENDOMETRIAL THICKNESS ON LIVE BIRTH RATES IN PATIENTS
UNDERGOING ASSISTED REPRODUCTIVE TECHNOLOGY: AN ANALYSIS OF 4,086 ART
CYCLES.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT International-Federation-of-Fertility-Societies 21st World Congress on
Fertility and Sterility / 69th Annual Meeting of the
American-Society-for-Reproductive-Medicine
CY OCT 12-17, 2013
CL Boston, MA
SP Int Federat Fertil Soc, Amer Soc Reprod Med
C1 [Zarek, S. M.; Hill, M. J.; Eltoukhi, H. M.; DeCherney, A. H.; Wolff, E. F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Widra, E.] Shady Grove Fertil Ctr, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 1
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 SEP
PY 2013
VL 100
IS 3
SU S
MA O-415
BP S126
EP S126
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AQ1PY
UT WOS:000342554500412
ER
PT J
AU Zarek, SM
Hill, MJ
Eltoukhi, HM
Richter, KS
DeCherney, AH
Wolff, EF
AF Zarek, S. M.
Hill, M. J.
Eltoukhi, H. M.
Richter, K. S.
DeCherney, A. H.
Wolff, E. F.
TI RACE/ETHNICITY ASSOCIATED WITH INCREASED PEAK ENDOMETRIAL THICKNESS AND
DECREASED LIVE BIRTH RATE: AN ANALYSIS OF 4,086 ASSISTED REPRODUCTIVE
TECHNOLOGY (ART) CYCLES
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT International-Federation-of-Fertility-Societies 21st World Congress on
Fertility and Sterility / 69th Annual Meeting of the
American-Society-for-Reproductive-Medicine
CY OCT 12-17, 2013
CL Boston, MA
SP Int Federat Fertil Soc, Amer Soc Reprod Med
C1 [Zarek, S. M.; Hill, M. J.; Eltoukhi, H. M.; DeCherney, A. H.; Wolff, E. F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Richter, K. S.] Shady Grove Fertil Ctr, Rockville, MD USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
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 SEP
PY 2013
VL 100
IS 3
SU S
MA O-266
BP S81
EP S81
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AQ1PY
UT WOS:000342554500265
ER
PT J
AU Duan, XH
Markello, T
Adams, D
Toro, C
Tifft, C
Gahl, WA
Boerkoel, CF
AF Duan, Xiaohong
Markello, Thomas
Adams, David
Toro, Camilo
Tifft, Cynthia
Gahl, William A.
Boerkoel, Cornelius F.
TI Cultural differences define diagnosis and genomic medicine practice:
implications for undiagnosed diseases program in China
SO FRONTIERS OF MEDICINE
LA English
DT Editorial Material
DE genetics; cultural differences; undiagnosed diseases program
AB Despite the current acceleration and increasing leadership of Chinese genetics research, genetics and its clinical application have largely been imported to China from the Occident. Neither genetics nor the scientific reductionism underpinning its clinical application is integral to the traditional Chinese worldview. Given that disease concepts and their incumbent diagnoses are historically derived and culturally meaningful, we hypothesize that the cultural expectations of genetic diagnoses and medical genetics practice differ between the Occident and China. Specifically, we suggest that an undiagnosed diseases program in China will differ from the recently established Undiagnosed Diseases Program at the United States National Institutes of Health; a culturally sensitive concept will integrate traditional Chinese understanding of disease with the scientific reductionism of Occidental medicine.
C1 [Duan, Xiaohong] Fourth Mil Med Univ, Sch Stomatol, Clin Oral Rare Dis & Genet Dis, Dept Oral Biol, Xian 710032, Peoples R China.
[Markello, Thomas; Adams, David; Toro, Camilo; Tifft, Cynthia; Gahl, William A.; Boerkoel, Cornelius F.] NIH, Undiagnosed Dis Program, Off Rare Dis Res, Bethesda, MD 20892 USA.
[Markello, Thomas; Adams, David; Toro, Camilo; Tifft, Cynthia; Gahl, William A.; Boerkoel, Cornelius F.] NHGRI, Bethesda, MD 20892 USA.
RP Duan, XH (reprint author), Fourth Mil Med Univ, Sch Stomatol, Clin Oral Rare Dis & Genet Dis, Dept Oral Biol, Xian 710032, Peoples R China.
EM xhduan@fmmu.edu.cn
FU Intramural NIH HHS [Z99 HG999999, ZIA HG000215-10]
NR 37
TC 0
Z9 1
U1 2
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 2095-0217
EI 2095-0225
J9 FRONT MED-PRC
JI Front. Med.
PD SEP
PY 2013
VL 7
IS 3
BP 389
EP 394
DI 10.1007/s11684-013-0281-3
PG 6
WC Oncology; Medicine, Research & Experimental
SC Oncology; Research & Experimental Medicine
GA V41UO
UT WOS:000209571300015
PM 23856975
ER
PT J
AU de Bielke, MGS
Yancoski, J
Oliveira, JB
Danielian, S
AF de Bielke, M. G. Simesen
Yancoski, J.
Oliveira, J. B.
Danielian, S.
TI Particular Behavior of an Extracellular Missense FAS Mutation (p.C107Y)
Identified in High Frequency in Argentinean Patients with Autoimmune
Lymphoproliferative Syndrome
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 3rd Meeting of the Latin-American-Society-for-Immunodeficiencies (LASID)
CY OCT 17-19, 2013
CL Santiago, CHILE
SP Latin Amer Soc Immunodeficiencies
C1 Hosp Peditaria Garrahan, Buenos Aires, DF, Argentina.
[de Bielke, M. G. Simesen; Yancoski, J.; Oliveira, J. B.; Danielian, S.] NIH, Serv Immunol, Dept Lab Med, Ctr Clin, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 SEP
PY 2013
VL 33
SU 3
MA 55
BP S116
EP S116
PG 1
WC Immunology
SC Immunology
GA AY1ZI
UT WOS:000347388100036
ER
PT J
AU Coller-Monarez, S
Groseclose, SL
Kurilla, MG
Berg, JM
AF Coller-Monarez, Susan
Groseclose, Samuel L.
Kurilla, Michael G.
Berg, Jeremy M.
TI High Priority Preparedness Research and Its Support
SO JOURNAL OF PUBLIC HEALTH MANAGEMENT AND PRACTICE
LA English
DT Editorial Material
DE federal support; Centers for Disease Control and Prevention; National
Institutes of Health; preparedness; Department of Homeland Security
AB The US Federal Government has considerable interest in supporting research into preparedness. Because of the diverse nature of possible threats and the responsibilities of different agencies, a number of different programs have been developed. Perspectives from representatives from 3 of the leading agencies; the Department of Homeland Security, the Centers from Disease Control and Prevention, and the National Institutes of Health, are described herein.
C1 [Coller-Monarez, Susan] Dept Homeland Secur, Threat Characterizat & Attribut Branch, Chem & Biol Def Div, Sci & Technol Directorate, Alexandria, VA USA.
[Groseclose, Samuel L.] Ctr Dis Control & Prevent, Sci & Policy Hlth Practice, Off Publ Hlth Preparedness & Response, Atlanta, GA USA.
[Kurilla, Michael G.] NIAID, Off Biodef Res Resources & Translat Res, NIH, Bethesda, MD 20892 USA.
[Kurilla, Michael G.] NIAID, Biodef Product Dev, Div Microbiol & Infect Dis, NIH, Bethesda, MD 20892 USA.
[Berg, Jeremy M.] Univ Pittsburgh, Sci Strategy & Planning Hlth Sci, Pittsburgh, PA 15213 USA.
[Berg, Jeremy M.] Univ Pittsburgh, Dept Computat & Syst Biol, 3550 Terrace St, Pittsburgh, PA USA.
RP Berg, JM (reprint author), Univ Pittsburgh, Dept Computat & Syst Biol, 3550 Terrace St, Pittsburgh, PA USA.
EM jberg@pitt.edu
OI Berg, Jeremy/0000-0003-3022-0963
NR 4
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 1078-4659
EI 1550-5022
J9 J PUBLIC HEALTH MAN
JI J. Public Health Manag. Pract.
PD SEP-OCT
PY 2013
VL 19
SU 2
BP S9
EP S11
DI 10.1097/PHH.0b013e3182972287
PG 3
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA V43KM
UT WOS:000209680300004
PM 23903401
ER
PT J
AU Linkenhoker, JR
Linton, CGG
AF Linkenhoker, Jan R.
Linton, C. G. Garry
TI Effect of Nesting Material on Body Weights of Mice Infected with
Toxoplasma gondii
SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE
LA English
DT Article
ID ENVIRONMENTAL ENRICHMENT; LABORATORY RODENTS; C57BL/6J MICE; BEHAVIOR;
BALB/C
AB Toxoplasmosis, a disease caused by the parasitic protozoan Toxoplasma gondii, can cause a number of clinical signs in mice, including weight loss. This weight loss likely is related to the host immune response and is important to monitor in Toxoplasma studies. Several studies have demonstrated that nesting material can affect body weights of mice. We therefore sought to assess the effects of nesting material on body weights of mice infected with Toxoplasma. We housed mice with or without nesting material and weighed and clinically assessed them twice weekly for 30 days prior to and 5 wk after Toxoplasma inoculation. Nesting material did not significantly alter the weights of mice after Toxoplasma inoculation but did decrease rates of growth prior to inoculation. Nesting material did not affect the clinical outcome of Toxoplasma infections, supporting the provision of nesting material in mouse Toxoplasma experiments.
C1 [Linkenhoker, Jan R.; Linton, C. G. Garry] NIH, Dept Hlth & Human Serv, Off Director, Off Res Serv,Div Vet Resources, Bethesda, MD 20892 USA.
RP Linkenhoker, JR (reprint author), NIH, Dept Hlth & Human Serv, Off Director, Off Res Serv,Div Vet Resources, Bethesda, MD 20892 USA.
EM linkenhj@od.nih.gov
FU Intramural Research Program of the NIH Division of Veterinary Resources;
National Cancer Institute
FX We acknowledge Dr Yin Liu and Ms Love Wade for assistance with this
study and Dr Tanya Burkholder for thoughtful review of this manuscript.
This research was supported by the Intramural Research Program of the
NIH Division of Veterinary Resources and the National Cancer Institute.
The views and opinions provided are those of the authors and do not
reflect the official policy or positions of the NIH, Department of
Health and Human Services, or United States Government.
NR 14
TC 1
Z9 1
U1 0
U2 1
PU AMER ASSOC LABORATORY ANIMAL SCIENCE
PI MEMPHIS
PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA
SN 1559-6109
J9 J AM ASSOC LAB ANIM
JI J. Amer. Assoc. Lab. Anim. Sci.
PD SEP
PY 2013
VL 52
IS 5
BP 531
EP 533
PG 3
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA AN7VZ
UT WOS:000340810400003
PM 24041206
ER
PT J
AU Mendoza, A
Gharpure, R
Dennis, J
Webster, JD
Smedley, J
Khanna, C
AF Mendoza, Arnulfo
Gharpure, Radhika
Dennis, John
Webster, Joshua D.
Smedley, Jeremy
Khanna, Chand
TI A Novel Noninvasive Method for Evaluating Experimental Lung Metastasis
in Mice
SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE
LA English
DT Article
ID MODELS; TUMOR
AB Metastasis remains the most significant problem in the field of cancer. The biologic complexity that characterizes metastasis requires relevant in vivo models. When using murine models for pulmonary metastasis, longitudinal studies are valuable for following the progression of metastatic burden. Currently, the progression of pulmonary metastatic burden in experimental mice over time is monitored through advanced imaging approaches or the clinical assessment of morbidity. Because clinical signs of morbidity are often vague and unpredictable, an inexpensive and reproducible method to detect advanced metastatic burden-before the development of mortality-is needed. We have developed a noninvasive technique for assessing pulmonary metastatic burden in laboratory mice. The pulmonary assessment of advanced metastasis (PAAM) test is performed by restraining an awake mouse and gently applying pressure with the index finger under the xiphoid process. This pressure reduces the diaphragmatic component to respiration. Mice with advanced lung metastases show transient signs of respiratory distress within 3 s of the application of this pressure. Using PAAM in 4 distinct models (including sarcoma and mammary carcinoma histologies) of experimental (tail vein) pulmonary metastasis (n = 114 mice), among 3 independent evaluators yielded 94% positive and negative predictive values, which were validated by histologic assessment of postmortem lung tissue. PAAM is a simple, reproducible, and efficient method to assist in the detection of advanced pulmonary metastasis in mice and contributes to their humane care during longitudinal studies.
C1 [Mendoza, Arnulfo; Gharpure, Radhika; Khanna, Chand] NCI, Tumor & Metastasis Biol Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Webster, Joshua D.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD USA.
[Dennis, John; Smedley, Jeremy] SAIC Frederick Lab Anim Sci Program, Bethesda, MD USA.
RP Khanna, C (reprint author), NCI, Tumor & Metastasis Biol Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
EM khannac@mail.nih.gov
OI Smedley, Jeremy/0000-0003-3369-4662
FU NIH (National Cancer Institute, Bethesda Maryland)
FX This research was supported by The Intramural Research Program of the
NIH (National Cancer Institute, Bethesda Maryland).
NR 12
TC 2
Z9 2
U1 0
U2 2
PU AMER ASSOC LABORATORY ANIMAL SCIENCE
PI MEMPHIS
PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA
SN 1559-6109
J9 J AM ASSOC LAB ANIM
JI J. Amer. Assoc. Lab. Anim. Sci.
PD SEP
PY 2013
VL 52
IS 5
BP 584
EP 589
PG 6
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA AN7VZ
UT WOS:000340810400012
PM 24041215
ER
PT J
AU Masedunskas, A
Porat-Shliom, N
Tora, M
Milberg, O
Weigert, R
AF Masedunskas, Andrius
Porat-Shliom, Natalie
Tora, Muhibullah
Milberg, Oleg
Weigert, Roberto
TI Intravital Microscopy for Imaging Subcellular Structures in Live Mice
Expressing Fluorescent Proteins
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Article
DE Cellular Biology; Issue 79; Microscopy; Confocal Microscopy;
Fluorescence; Multiphoton; Exocytosis; Cell Biology; animal biology;
animal models; Intravital Microscopy; Salivary glands; Exocytosis; In
Vivo Imaging
AB Here we describe a procedure to image subcellular structures in live rodents that is based on the use of confocal intravital microscopy. As a model organ, we use the salivary glands of live mice since they provide several advantages. First, they can be easily exposed to enable access to the optics, and stabilized to facilitate the reduction of the motion artifacts due to heartbeat and respiration. This significantly facilitates imaging and tracking small subcellular structures. Second, most of the cell populations of the salivary glands are accessible from the surface of the organ. This permits the use of confocal microscopy that has a higher spatial resolution than other techniques that have been used for in vivo imaging, such as two-photon microscopy. Finally, salivary glands can be easily manipulated pharmacologically and genetically, thus providing a robust system to investigate biological processes at a molecular level.
In this study we focus on a protocol designed to follow the kinetics of the exocytosis of secretory granules in acinar cells and the dynamics of the apical plasma membrane where the secretory granules fuse upon stimulation of the beta-adrenergic receptors. Specifically, we used a transgenic mouse that co-expresses cytosolic GFP and a membrane-targeted peptide fused with the fluorescent protein tandem-Tomato. However, the procedures that we used to stabilize and image the salivary glands can be extended to other mouse models and coupled to other approaches to label in vivo cellular components, enabling the visualization of various subcellular structures, such as endosomes, lysosomes, mitochondria, and the actin cytoskeleton.
C1 [Masedunskas, Andrius; Porat-Shliom, Natalie; Tora, Muhibullah; Milberg, Oleg; Weigert, Roberto] Natl Inst Dent & Craniofacial Res, Intracellular Membrane Trafficking Unit, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA.
[Masedunskas, Andrius] Univ N Carolina, Dept Biol, Chapel Hill, NC USA.
[Milberg, Oleg] Rutgers State Univ, Dept Chem & Biochem Engn, Piscataway, NJ 08855 USA.
[Milberg, Oleg] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08855 USA.
RP Weigert, R (reprint author), Natl Inst Dent & Craniofacial Res, Intracellular Membrane Trafficking Unit, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA.
EM weigertr@mail.nih.gov
OI Masedunskas, Andrius/0000-0002-4533-5467
FU Intramural Research Program of the NIH, National Institute of Dental and
Craniofacial Research
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Dental and Craniofacial Research.
NR 15
TC 3
Z9 3
U1 0
U2 1
PU JOURNAL OF VISUALIZED EXPERIMENTS
PI CAMBRIDGE
PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA
SN 1940-087X
J9 JOVE-J VIS EXP
JI J. Vis. Exp.
PD SEP
PY 2013
IS 79
AR UNSP e50558
DI 10.3791/50558
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA V36RI
UT WOS:000209228100019
ER
PT J
AU Brabletz, T
Lyden, D
Steeg, PS
Werb, Z
AF Brabletz, Thomas
Lyden, David
Steeg, Patricia S.
Werb, Zena
TI Roadblocks to translational advances on metastasis research
SO NATURE MEDICINE
LA English
DT Article
ID EPITHELIAL-MESENCHYMAL TRANSITION; CIRCULATING TUMOR-CELLS; CANCER
STEM-CELLS; BREAST-CANCER; DRUG-RESISTANCE; DOWN-REGULATION;
COLONIZATION; MICROENVIRONMENT; PROGRESSION; MODEL
C1 US Natl Canc Inst, Womens Canc Sect, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD USA.
Univ Freiburg Med Ctr, Dept Gen & Visceral Surg, Ctr Comprehens Canc, Freiburg, Germany.
Univ Freiburg Med Ctr, BIOSS Ctr Biol Signalling Studies, Freiburg, Germany.
Univ Calif San Francisco, Dept Anat, San Francisco, CA USA.
RP Brabletz, T (reprint author), US Natl Canc Inst, Womens Canc Sect, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD USA.
EM thomas.brabletz@uniklinik-freiburg.de; dcl2001@med.cornell.edu;
steegp@mail.nih.gov; zena.werb@ucsf.edu
FU NCI NIH HHS [R01 CA129523]
NR 60
TC 21
Z9 23
U1 3
U2 13
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
EI 1546-170X
J9 NAT MED
JI Nat. Med.
PD SEP
PY 2013
VL 19
IS 9
BP 1104
EP 1109
DI 10.1038/nm.3327
PG 6
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 213TP
UT WOS:000324083500023
PM 24013756
ER
PT J
AU Chen, Y
Schlessinger, D
Nagaraja, R
AF Chen, Y.
Schlessinger, D.
Nagaraja, R.
TI T antigen transformation reveals Tp53/RB-dependent route to PLAC1
transcription activation in primary fibroblasts
SO ONCOGENESIS
LA English
DT Article
DE large T antigen; transcription; NCOA2; RXR alpha; LXR; chromatin
AB PLAC1 (placenta-specific 1) is a gene that is placenta specific and transcribed very little, if at all, in any somatic tissue. It is nevertheless expressed in many cancer cell lines. To understand how cancer cells may activate the gene in nonexpressing cells, we found that a model is provided by classical transformation of normal fibroblasts by SV40 T antigen. T antigen derepressed the PLAC1 P1 promoter, with Tp53 and RB exerting critical and opposing actions and nuclear receptors, retinoid X receptor and liver X receptor, sharply increasing the level of expression.
C1 [Chen, Y.; Schlessinger, D.; Nagaraja, R.] NIA, Genet Lab, Baltimore, MD 21224 USA.
RP Nagaraja, R (reprint author), NIA, Genet Lab, NIH, Biomed Res Ctr,IRP, 251 Bayview Blvd,Room 10B117, Baltimore, MD 21224 USA.
EM nagarajar@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Institute on Aging
FX This work was entirely funded by the Intramural Research Program of the
National Institutes of Health, National Institute on Aging. We thank Drs
Wedong Wang and Paritosh Ghosh for critical reading of the manuscript
and suggestions.
NR 35
TC 2
Z9 2
U1 1
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 2157-9024
J9 ONCOGENESIS
JI Oncogenesis
PD SEP
PY 2013
VL 2
AR UNSP e67
DI 10.1038/oncsis.2013.31
PG 8
WC Oncology
SC Oncology
GA V36OH
UT WOS:000209220500001
PM 23999628
ER
PT J
AU Masood, R
Hochstim, C
Cervenka, B
Zu, S
Baniwal, SK
Patel, V
Kobielak, A
Sinha, UK
AF Masood, R.
Hochstim, C.
Cervenka, B.
Zu, S.
Baniwal, S. K.
Patel, V.
Kobielak, A.
Sinha, U. K.
TI A novel orthotopic mouse model of head and neck cancer and lymph node
metastasis
SO ONCOGENESIS
LA English
DT Article
DE head and neck squamous cell carcinoma genetics; metastasis;
epithelial-to-mesenchymal transition (EMT); cancer stem cells (CSCs)
AB Prognosis of head and neck squamous cell carcinoma (HNSCC) is largely determined by the extent of lymph node (LN) metastasis at diagnosis, and this appears to be controlled by cancer cell genetics. To examine the role of these genes in LN metastasis, we created a human-in-mouse orthotopic model of HNSCC and performed comparative microarray analysis of gene expression between populations of HNSCC cell lines derived before and after serial transplantation and in vivo metastasis in mice. Microarray analysis comparing the USC-HN3-GFP, USC-HN3-GFP-G1 and USC-HN3-GFP-G2 cell lines identified overexpression of genes implicated in epithelial-to-mesenchymal transition and the formation of cancer stem cells, including CAV-1, TLR-4 (Toll-like receptor 4), MMP-7 (matrix metalloproteinase 7), ALDH1A3, OCT-4 and TRIM-29. Ingenuity Pathway Analysis confirmed upregulation of respective gene signaling pathways in the USC-HN1-GFP-G2 cell line. Patient HNSCC samples from advanced stages overexpressed ALDH1A3, CAV-1 and MMP-7. Our results show that CAV-1, TLR-4, MMP-7, ALDH1A3, OCT-4 and TRIM-29 have increased expression in HNSCC cells selected for an enhanced metastatic phenotype and suggest that these genes may have an important role in the metastatic potential of HNSCC cells. Inhibition of these genes may therefore have prognostic and therapeutic utility in HNSCC.
C1 [Masood, R.; Hochstim, C.; Cervenka, B.; Zu, S.; Kobielak, A.; Sinha, U. K.] Univ So Calif, Keck Sch Med, Dept Otolaryngol Head & Neck Surg, Los Angeles, CA 90033 USA.
[Baniwal, S. K.] Univ So Calif, Keck Sch Med, Dept Orthoped Surg, Los Angeles, CA 90033 USA.
[Patel, V.] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA.
RP Masood, R (reprint author), Univ So Calif, Keck Sch Med, Dept Otolaryngol Head & Neck Surg, HMP 903,2011 Zonal Ave, Los Angeles, CA 90033 USA.
EM masood@usc.edu
FU Health Research Association; RAM capital; Zumberge foundation
FX We thank Susan McDonald for her help in the patients' chart. We also
thank Raj Dedhia and Farshad Chowdhury for doing the chart review of all
the patients and proofreading the manuscript. This work was supported by
the generous grants from the Health Research Association and RAM
capital. RM had complete access to the data used in this manuscript and
is without any conflict of interest. Dr Baniwal was supported from the
Zumberge foundation.
NR 36
TC 12
Z9 12
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 2157-9024
J9 ONCOGENESIS
JI Oncogenesis
PD SEP
PY 2013
VL 2
AR UNSP e68
DI 10.1038/oncsis.2013.33
PG 8
WC Oncology
SC Oncology
GA V36OH
UT WOS:000209220500002
PM 24018643
ER
PT J
AU Coll, JA
Campbell, A
Chalmers, NI
AF Coll, James A.
Campbell, Alison
Chalmers, Natalia I.
TI Effects of Glass Ionomer Temporary Restorations on Pulpal Diagnosis and
Treatment Outcomes in Primary Molars
SO PEDIATRIC DENTISTRY
LA English
DT Article
DE PULP THERAPY; ENDODONTICS; GLASS IONOMER CEMENTS; PRIMARY MOLARS
ID MINERAL TRIOXIDE AGGREGATE; MICROBIOLOGICAL ANALYSIS; CARIOUS DENTIN;
PRIMARY TEETH; CARIES; FORMOCRESOL; PULPOTOMY; THERAPY; CEMENT; TRIAL
AB Purpose: To evaluate 1) if glass ionomer interim temporary restorations (ITR) placed for 1-3 months prior to vital pulp therapy (VPT) improved accuracy of diagnosing the pulp's clinical status and subsequent VPT success, and 2) the effect of the location of the carious lesion on VPT. Methods: Primary molars (N=117) receiving pulp therapy with or without ITR were evaluated retrospectively All teeth had caries extending >50 percent into dentin; caries lesion location was identified (proximal or non-proximal). Two examiners rated pulp status assessment, caries location, and pulp treatment, and correlated treatment outcomes after a mean of 34.7 months to these factors. Results: VPT failed more often in first primary molars (P<.001) than in second primary molars. Using ITR improved diagnosis of the pulp status, clinical success of VPT, (P=.013) and first molar VPT success (P=.02). First primary molars had more proximal lesions than second molars (P<.001). Failure of VPT was greater for teeth with proximal lesions (P=.03). Use of ITR significantly improved VPT in teeth with proximal lesions (P=.007) but not non-proximal lesions (P=.38). Conclusions: ITR placed prior to VPT improved pulpal diagnosis and VPT outcomes. Vital pulp therapy was less successful in primary molars with proximal lesions, and ITR significantly improved the success.
C1 [Coll, James A.] Univ Maryland, Sch Dent, Dept Pediat Dent, Baltimore, MD 21201 USA.
[Chalmers, Natalia I.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA.
RP Coll, JA (reprint author), Univ Maryland, Sch Dent, Dept Pediat Dent, Baltimore, MD 21201 USA.
EM dmd1@comcat.net
NR 32
TC 1
Z9 1
U1 1
U2 2
PU AMER ACAD PEDIATRIC DENTISTRY
PI CHICAGO
PA 211 E CHICAGO AVENUE SUITE 1036, CHICAGO, IL 60611-2616 USA
SN 0164-1263
EI 1942-5473
J9 PEDIATR DENT
JI Pediatr. Dent.
PD SEP-OCT
PY 2013
VL 35
IS 5
BP 416
EP 421
PG 6
WC Dentistry, Oral Surgery & Medicine; Pediatrics
SC Dentistry, Oral Surgery & Medicine; Pediatrics
GA AP8NR
UT WOS:000342336200004
PM 24290553
ER
PT J
AU Meganck, JA
Begun, DL
McElderry, JD
Swick, A
Kozloff, KM
Goldstein, SA
Morris, MD
Marini, JC
Caird, MS
AF Meganck, J. A.
Begun, D. L.
McElderry, J. D.
Swick, A.
Kozloff, K. M.
Goldstein, S. A.
Morris, M. D.
Marini, J. C.
Caird, M. S.
TI Fracture healing with alendronate treatment in the Brtl/ plus mouse
model of osteogenesis imperfecta
SO BONE
LA English
DT Article
DE Osteogenesis imperfecta; Bisphosphonates; Bone; Rodent; Fracture repair
ID HYPERPLASTIC CALLUS FORMATION; POLARIZED-LIGHT MICROSCOPY; ZOLEDRONIC
ACID; BISPHOSPHONATE INCADRONATE; BONE STRENGTH; CHILDREN; PAMIDRONATE;
COLLAGEN; REPAIR; RATS
AB Osteogenesis imperfecta (OI) is a heritable bone dysplasia characterized by increased skeletal fragility. Patients are often treated with bisphosphonates to attempt to reduce fracture risk. However, bisphosphonates reside in the skeleton for many years and long-term administration may impact bone material quality. Acutely, there is concern about risk of non-union of fractures that occur near the time of bisphosphonate administration. This study investigated the effect of alendronate, a potent aminobisphosphonate, on fracture healing. Using the Brtl/+ murine model of type IV OI, tibial fractures were generated in 8-week-old mice that were untreated, treated with alendronate before fracture, or treated before and after fracture. After 2, 3, or 5 weeks of healing, tibiae were assessed using microcomputed tomography (mu CT), torsion testing, quantitative histomorphometry, and Raman microspectroscopy. There were no morphologic, biomechanical or histomorphometric differences in callus between untreated mice and mice that received alendronate before fracture. Alendronate treatment before fracture did not cause a significant increase in cartilage retention in fracture callus. Both Brtl/+ and WT mice that received alendronate before and after fracture had increases in the callus volume, bone volume fraction and torque at failure after 5 weeks of healing. Raman microspectroscopy results did not show any effects of alendronate in wild-type mice, but calluses from Brtl+ mice treated with alendronate during healing had a decreased mineral-to-matrix ratio, decreased crystallinity and an increased carbonate-to-phosphate ratio. Treatment with alendronate altered the dynamics of healing by preventing callus volume decreases later in the healing process. Fracture healing in Brtl/+ untreated animals was not significantly different from animals in which alendronate was halted at the time of fracture. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Meganck, J. A.; Begun, D. L.; Swick, A.; Kozloff, K. M.; Goldstein, S. A.; Caird, M. S.] Univ Michigan, Dept Orthopaed Surg, Orthopaed Res Labs, Ann Arbor, MI 48109 USA.
[Meganck, J. A.; Begun, D. L.; Swick, A.; Kozloff, K. M.; Goldstein, S. A.] Univ Michigan, Dept Biomed Engn, Ann Arbor, MI 48109 USA.
[McElderry, J. D.; Morris, M. D.] Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA.
[Marini, J. C.] NICHHD, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD 20892 USA.
RP Caird, MS (reprint author), Univ Michigan, Dept Orthopaed Surg, Mott Childrens Hosp, 1540 E Med Ctr Dr, Ann Arbor, MI 48109 USA.
EM Jeff.Meganck@caliperls.com; dbegun@umich.edu; jdmac@umich.edu;
aswick3@gmail.com; kenkoz@umich.edu; stevegld@umich.edu;
mdmorris@umich.etlu; oidoc@helix.nih.gov; sugiyama@med.umich.edu
FU National Science Foundation; University of Michigan Musculoskeletal Core
Center [NIH AR46024]; regenerative sciences training grant [NIH T90
DK070071]; University of Michigan Department of Orthopaedic Surgery;
National Institutes of Health [R01 AR047969]; NICHD
FX The authors would like to thank Bonnie Nolan, Kathy Sweet, Sharon Reske,
Xixi Wang, Jason Combs, Dennis Kayner, and Charles Roehm. Thanks also to
Ling ling Zhang for statistical support. The authors would also like to
acknowledge support from the National Science Foundation Graduate
Research Fellowship Program (JAM), the University of Michigan
Musculoskeletal Core Center (SAG; NIH AR46024), the regenerative
sciences training grant (SAG; NIH T90 DK070071), the University of
Michigan Department of Orthopaedic Surgery (MSC), the National
Institutes of Health (MDM; R01 AR047969), and NICHD Intramural Funding
(JCM). These funding sources did not have involvement in the study
design; collection, analysis, or interpretation of data; or in the
report or its publication submission.
NR 54
TC 11
Z9 11
U1 3
U2 24
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 8756-3282
J9 BONE
JI Bone
PD SEP
PY 2013
VL 56
IS 1
BP 204
EP 212
DI 10.1016/j.bone.2013.06.003
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 189WS
UT WOS:000322299600028
PM 23774443
ER
PT J
AU Rossi, PIA
Musante, I
Summa, M
Pittaluga, A
Emionite, L
Ikehata, M
Rastaldi, MP
Ravazzolo, R
Puliti, A
AF Rossi, Pia Irene Anna
Musante, Ilaria
Summa, Maria
Pittaluga, Anna
Emionite, Laura
Ikehata, Masami
Rastaldi, Maria Pia
Ravazzolo, Roberto
Puliti, Aldamaria
TI Compensatory Molecular and Functional Mechanisms in Nervous System of
the Grm1(crv4) Mouse Lacking the mGlu1 Receptor: A Model for Motor
Coordination Deficits
SO CEREBRAL CORTEX
LA English
DT Article
DE evoked-glutamate release; Grm1(crv4) mouse; mGlu1 receptor; mGlu5
receptor; mouse cortex
ID METABOTROPIC GLUTAMATE RECEPTORS; CEREBELLAR PURKINJE-CELLS; LONG-TERM
POTENTIATION; MICE LACKING; MUTANT MICE; RAT-BRAIN; EXPRESSION;
DIFFERENTIATION; EXOCYTOSIS; SURVIVAL
AB The metabotropic glutamate type 1 (mGlu1) and type 5 (mGlu5) receptors, the only members of group I mGlu receptors, are implicated in synaptic plasticity and mechanisms of feedback control of glutamate release. They exhibit nearly complementary distributions throughout the central nervous system, well evident in the cerebellum, where mGlu1 receptor is most intensely expressed while mGlu5 receptor is not. Despite their different distribution, they show a similar subcellular localization and use common transducing pathways. We recently described the Grm1(crv4) mouse with motor coordination deficits and renal anomalies caused by a spontaneous mutation inactivating the mGlu1 receptor. To define the neuropathological mechanisms in these mice, we evaluated expression and function of the mGlu5 receptor in cerebral and cerebellar cortices. Western blot and immunofluorescence analyses showed mGlu5 receptor overexpression. Quantitative reverse transcriptase-polymerase chain reaction results indicated that the up-regulation is already evident at RNA level. Functional studies confirmed an enhanced glutamate release from cortical cerebral and cerebellar synaptosomes when compared with wild-type that is abolished by the mGlu5 receptor-specific inhibitor, 2-methyl-6-(phenylethynyl) pyridine hydrochloride (MPEP). Finally, acute MPEP treatment of Grm1(crv4/crv4) mice induced an evident although incomplete improvement of motor coordination, suggesting that mGlu5 receptors enhanced activity worsens, instead of improving, the motor-coordination defects in the Grm1(crv4/crv4) mice.
C1 [Rossi, Pia Irene Anna; Musante, Ilaria; Ravazzolo, Roberto; Puliti, Aldamaria] Gaslini Inst, Mol Genet & Cytogenet Unit, Genoa, Italy.
[Rossi, Pia Irene Anna; Musante, Ilaria; Ravazzolo, Roberto; Puliti, Aldamaria] Univ Genoa, Dept Pediat Sci, Genoa, Italy.
[Summa, Maria; Pittaluga, Anna] Univ Genoa, Dept Expt Med, Sect Pharmacol & Toxicol, Genoa, Italy.
[Emionite, Laura] Natl Canc Inst, Anim Facil, Genoa, Italy.
[Ikehata, Masami; Rastaldi, Maria Pia] Fdn IRCCS Osped Maggiore Policlin, Renal Res Lab, Milan, Italy.
[Ikehata, Masami; Rastaldi, Maria Pia] Fdn DAmico Ric Malattie Renali, Milan, Italy.
RP Puliti, A (reprint author), G Gaslini Inst Children, Mol Genet Lab, Largo G Gaslini 5, I-16148 Genoa, Italy.
EM apuliti@unige.it
RI Pittaluga, Anna/C-5960-2008; Puliti, Aldamaria/K-7866-2016; IKEHATA,
MASAMI/H-8020-2016
OI Puliti, Aldamaria/0000-0001-9310-6514; IKEHATA,
MASAMI/0000-0001-9835-9991
FU Italian Ministry of Health [RFPS-4-631972]; Italian 'Ministero
dell'Istruzione, dell'Universita e della Ricerca Scientifica' (MIUR)
FX This work was supported by RFPS-4-631972 grant 'Genetic Bases of Birth
Defects' from the Italian Ministry of Health to R. R. and by grant from
the Italian 'Ministero dell'Istruzione, dell'Universita e della Ricerca
Scientifica' (MIUR) to A.P.
NR 51
TC 4
Z9 4
U1 0
U2 12
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1047-3211
J9 CEREB CORTEX
JI Cereb. Cortex
PD SEP
PY 2013
VL 23
IS 9
BP 2179
EP 2189
DI 10.1093/cercor/bhs200
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 194VP
UT WOS:000322661100015
PM 22791805
ER
PT J
AU Hunter, AM
Leuchter, AF
Power, RA
Muthen, B
McGrath, PJ
Lewis, CM
Cook, IA
Garriock, HA
McGuffin, P
Uher, R
Hamilton, SP
AF Hunter, Aimee M.
Leuchter, Andrew F.
Power, Robert A.
Muthen, Bengt
McGrath, Patrick J.
Lewis, Cathryn M.
Cook, Ian A.
Garriock, Holly A.
McGuffin, Peter
Uher, Rudolf
Hamilton, Steven P.
TI A genome-wide association study of a sustained pattern of antidepressant
response
SO JOURNAL OF PSYCHIATRIC RESEARCH
LA English
DT Article
DE Antidepressant; Genetics; STAR*D; GENDEP; Growth mixture modeling;
Citalopram
ID STAR-ASTERISK-D; CHONDROITIN SULFATE PROTEOGLYCANS; MAJOR DEPRESSIVE
DISORDER; SET ENRICHMENT ANALYSIS; CLINICAL-PRACTICE; GENETIC-VARIATION;
PHARMACOGENETICS; TRAJECTORIES; EFFICACY; GENDEP
AB Genome-wide association studies (GWAS) have failed to replicate common genetic variants associated with antidepressant response, as defined using a single endpoint. Genetic influences may be discernible by examining individual variation between sustained versus unsustained patterns of response, which may distinguish medication effects from non-specific, or placebo responses to active medication. We conducted a GWAS among 1116 subjects with Major Depressive Disorder from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial who were characterized using Growth Mixture Modeling as showing a sustained versus unsustained pattern of clinical response over 12 weeks of treatment with citalopram. Replication analyses examined 585 subjects from the Genome-based Therapeutic Drugs for Depression (GENDEP) trial. The strongest association with sustained as opposed to unsustained response in STAR*D involved a single nucleotide polymorphism (SNP; rs10492002) within the acyl-CoA synthetase short-chain family member 3 gene (ACSS3, p-value =4.5 x 10(-6), odds ratio = 0.61). No SNPs met our threshold for genome-wide significance. SNP data were available in GENDEP for 18 of the top 25 SNPs in STAR*D. The most replicable association was with SNP rs7816924 (p = 0.008, OR= 1.58); no SNP met the replication p-value threshold of 0.003. Joint analysis of these 18 SNPs resulted in the strongest signal coming from rs7816924 (p = 2.11 x 10(-7)), which resides in chondroitin sulfate N-acetylgalactosaminyltransferase 1 gene (CSGALNACT1). An exploratory genetic pathway analysis revealed evidence for an involvement of the KEGG pathway of long-term potentiation (FDR=.02). Results suggest novel genetic associations to sustained response. (c) 2013 Elsevier Ltd. All rights reserved.
C1 [Hunter, Aimee M.; Leuchter, Andrew F.; Cook, Ian A.] Univ Calif Los Angeles, Dept Psychiat, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA.
[Power, Robert A.; Lewis, Cathryn M.; McGuffin, Peter; Uher, Rudolf] Kings Coll London, Inst Psychiat, London, England.
[Muthen, Bengt] Univ Calif Los Angeles, Grad Sch Educ & Informat Studies, Los Angeles, CA 90024 USA.
[McGrath, Patrick J.] Columbia Univ, Coll Physicians & Surg, New York State Psychiat Inst, Dept Psychiat, New York, NY 10027 USA.
[Garriock, Holly A.; Hamilton, Steven P.] Univ Calif San Francisco, Dept Psychiat, Inst Human Genet, San Francisco, CA 94143 USA.
[Garriock, Holly A.] NIMH, Div Dev Trajectories, Bethesda, MD USA.
[Uher, Rudolf] Dalhousie Univ, Dept Psychiat, Halifax, NS, Canada.
RP Hunter, AM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, 760 Westwood Plaza,Rm 57-455, Los Angeles, CA 90024 USA.
EM amhunter@ucla.edu
RI McGrath, Patrick/I-6410-2013; McGuffin, Peter/A-1565-2012; Uher,
Rudolf/A-5477-2008; Lewis, Cathryn/A-5225-2010; Power,
Robert/B-3482-2012;
OI McGrath, Patrick/0000-0001-7217-7321; McGuffin,
Peter/0000-0002-9888-2907; Uher, Rudolf/0000-0002-2998-0546; Lewis,
Cathryn/0000-0002-8249-8476; Garriock, Holly/0000-0002-0629-5917;
Hamilton, Steven/0000-0001-8106-6260
FU NIMH [N01MH90003, MH072802, 1R34MH085933-01]; European Commission
[LSHB-CT-2003-503428]; GlaxoSmithKline [G0701420]; UK National Institute
for Health Research of the Department of Health; U.K. Medical research
council; European Commission Innovative Medicine Initiative Joint
Undertaking (IMI-JU) [115008]; Canada Research Chairs program
FX Clinical data used in the GWAS were obtained from the limited access
datasets distributed from the NIMH-supported "Sequenced Treatment
Alternatives to Relieve Depression" (STAR*D) (Contract # N01MH90003 to
the University of Texas Southwestern Medical Center). Genotyping of the
STAR*D sample was supported by NIMH grant MH072802 to S.P. Hamilton.
Analysis of STAR*D clinical data and response trajectories was supported
by NIMH grant 1R34MH085933-01 to A.M. Hunter. This manuscript reflects
the views of the authors and may not reflect the opinions or views of
the STAR*D Study Investigators or the NIH.; Data for replication
analyses were obtained from the GENDEP project which was funded by the
European Commission Framework 6 grant, EC Contract Ref.:
LSHB-CT-2003-503428. H. Lundbeck provided nortriptyline and escitalopram
for the GENDEP study. GlaxoSmithKline and the UK National Institute for
Health Research of the Department of Health contributed to the funding
of the sample collection at the Institute of Psychiatry London. GENDEP
genotyping was funded by a joint grant from the U.K. Medical research
council and GlaxoSmithKline (G0701420) and the European Commission
Innovative Medicine Initiative Joint Undertaking (IMI-JU) grant no
115008. R. Uher is supported by the Canada Research Chairs program
(http://www.chairs-chaires.gc.ca/) and the European Commission
Innovative Medicine Initiative Joint Undertaking (IMI-JU) grant no
115008.
NR 41
TC 16
Z9 17
U1 0
U2 16
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0022-3956
J9 J PSYCHIATR RES
JI J. Psychiatr. Res.
PD SEP
PY 2013
VL 47
IS 9
BP 1157
EP 1165
DI 10.1016/j.jpsychires.2013.05.002
PG 9
WC Psychiatry
SC Psychiatry
GA 191LF
UT WOS:000322413800005
PM 23726668
ER
PT J
AU Teicher, BA
AF Teicher, Beverly A.
TI Perspective: Opportunities in recalcitrant, rare and neglected tumors
SO ONCOLOGY REPORTS
LA English
DT Article
DE pancreatic cancer; sarcoma small cell lung cancer; recalicitrant tumors;
rare tumors; neglected tumors
ID CELL LUNG-CANCER; PANCREATIC-CANCER; HIF-1 INHIBITORS; SOLID TUMORS;
IN-VITRO; ANTICANCER; EXPRESSION; LINES; THERAPY; HYPOXIA
AB The 'Recalcitrant Cancer Research Act of 2012' defines recalcitrant cancers as having a 5-year survival rate of <20% and estimated to cause the death of at least 30,000 individuals in the US each year. Cancers specifically mentioned in the act are lung and pancreatic cancers. In addition to recalcitrant tumors, rare tumors are often neglected in the drug discovery arena. Sarcomas are similar to 1% of cancers. The NCI Specialized Programs of Research Excellence (SPOREs) provide disease-focused cancer center grants specifically to accelerate the impact of laboratory research on the treatment of patients. There are 3 SPOREs focused on pancreatic cancer, 7 SPOREs focused on lung cancer and 1 SPORE focused on sarcoma. Through the Developmental Therapeutics Program (DTP), NCI maintains the infrastructure and expertise for the operation of cell-free and cell-based high-, medium- and low-throughput assays. The current effort is on sarcoma, SCLC and pancreatic lines. The DTP functional genomics laboratory provides molecular analyses including gene expression microarrays, exon arrays, microRNA arrays, multiplexing gene assays, plus others as tools to identify potential drug targets and to determine the role of selected genes in the mechanism(s) of drug action and cellular responses to stressors. The DTP tumor microenvironment laboratory focuses on the discovery of targets and the development of therapeutic strategies targeting the tumor microenvironment and physiological abnormalities of tumors resulting from environmental factors or alterations in metabolic enzymes. The DTP maintains a group focused on determining the mechanism(s) of action and identifying potential surrogate markers of activity for select compounds integrating proteomics, transcriptomics and molecular biology platforms. In conclusion, the NCI has active SPORE programs and an internal effort focused on recalcitrant, rare and neglected cancers which are generating data toward improving treatment of these difficult diseases.
C1 NCI, Mol Pharmacol Branch, Dev Therapeut Program, Bethesda, MD 20892 USA.
RP Teicher, BA (reprint author), NCI, Mol Pharmacol Branch, Dev Therapeut Program, Room 4-W602,9606 Med Ctr Dr,MSC 9735, Bethesda, MD 20892 USA.
EM teicherba@mail.nih.gov
NR 51
TC 4
Z9 4
U1 0
U2 9
PU SPANDIDOS PUBL LTD
PI ATHENS
PA POB 18179, ATHENS, 116 10, GREECE
SN 1021-335X
EI 1791-2431
J9 ONCOL REP
JI Oncol. Rep.
PD SEP
PY 2013
VL 30
IS 3
BP 1030
EP 1034
DI 10.3892/or.2013.2581
PG 5
WC Oncology
SC Oncology
GA 191AJ
UT WOS:000322384700002
PM 23820887
ER
PT J
AU Birbaumer, N
Ayala, GG
Cohen, L
Murguialday, AR
AF Birbaumer, Niels
Ayala, Guillermo Gallegos
Cohen, Leonardo
Murguialday, Ander Ramos
TI BRAIN-MACHINE-INTERFACES (BMI) IN COMPLETE PARALYSIS
SO PSYCHOPHYSIOLOGY
LA English
DT Meeting Abstract
CT 53rd Annual Meeting of the Society-for-Psychophysiological-Research
CY OCT 02-06, 2013
CL Florence, ITALY
SP Soc Psychophysiol Res
DE Paralysis; Brain-Machine-Interface; Stroke
C1 [Birbaumer, Niels; Ayala, Guillermo Gallegos; Murguialday, Ander Ramos] Univ Tubingen, Tubingen, Germany.
[Cohen, Leonardo] NINDS, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0048-5772
J9 PSYCHOPHYSIOLOGY
JI Psychophysiology
PD SEP
PY 2013
VL 50
SU 1
SI SI
BP S40
EP S41
PG 2
WC Psychology, Biological; Neurosciences; Physiology; Psychology;
Psychology, Experimental
SC Psychology; Neurosciences & Neurology; Physiology
GA 199LH
UT WOS:000322995500231
ER
PT J
AU Esposito, G
Nakazawa, J
Venuti, P
Bornstein, MH
AF Esposito, Gianluca
Nakazawa, Jun
Venuti, Paola
Bornstein, Marc H.
TI Componential deconstruction of infant distress vocalizations via
tree-based models: A study of cry in autism spectrum disorder and
typical development
SO RESEARCH IN DEVELOPMENTAL DISABILITIES
LA English
DT Article
DE Cry; Autism; Autistic disorder; Perception of cry in Japan; Tree-based
models; Perception
ID YOUNG-CHILDREN; PERCEPTIONS; HYPOTHESIS
AB Understanding early episodes of cry is essential to improve caregiver-child interaction and child well-being. Caregiver perceptions of cry are based on interpretations of different acoustic characteristics of the cry, including the length of the pauses, the number of utterances, and the fundamental frequency. In this study, we used tree-based models to establish a hierarchy of effect in terms of how these acoustic characteristics influence perceptions of cries of children with autism compared to cries of typically developing children. In two studies, one in Italy and the other in Japan, we found that cries of children with autism are perceived more negatively. We also found that the length of the pauses, more than the number of utterances or fundamental frequency, determines listeners' negative perceptions. Implications for early caregiver-child interactions are discussed. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Esposito, Gianluca] RIKEN Brain Sci Inst, Unit Affiliat Social Behav, Wako, Saitama, Japan.
[Esposito, Gianluca; Venuti, Paola] Univ Trento, Dept Psychol & Cognit Sci, Trento, Italy.
[Nakazawa, Jun] Chiba Univ, Fac Educ, Dept Dev Sci, Chiba, Japan.
[Bornstein, Marc H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Esposito, G (reprint author), RIKEN Brain Sci Inst, Unit Affiliat Social Behav, Wako, Saitama, Japan.
EM gesposito@brain.riken.jp; nakazawa@faculty.chiba-u.jp
RI Esposito, Gianluca/B-1374-2012; Esposito, Gianluca/K-9353-2013
OI Esposito, Gianluca/0000-0002-9442-0254; Esposito,
Gianluca/0000-0002-9442-0254
FU Intramural NIH HHS [ZIA HD001119-25]
NR 39
TC 11
Z9 11
U1 1
U2 12
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0891-4222
J9 RES DEV DISABIL
JI Res. Dev. Disabil.
PD SEP
PY 2013
VL 34
IS 9
BP 2717
EP 2724
DI 10.1016/j.ridd.2013.05.036
PG 8
WC Education, Special; Rehabilitation
SC Education & Educational Research; Rehabilitation
GA 191OT
UT WOS:000322423200032
PM 23774058
ER
PT J
AU Jeong, J
Lisinski, I
Kadegowda, AKG
Shin, H
Wooding, FBP
Daniels, BR
Schaack, J
Mather, IH
AF Jeong, Jaekwang
Lisinski, Ivonne
Kadegowda, Anil K. G.
Shin, Hyunsu
Wooding, F. B. Peter
Daniels, Brian R.
Schaack, Jerome
Mather, Ian H.
TI A Test of Current Models for the Mechanism of Milk-Lipid Droplet
Secretion
SO TRAFFIC
LA English
DT Article
DE butyrophilin; exocrine biology; lactation; milk-lipid secretion; mouse;
perilipin-2; xanthine oxidoreductase
ID FAT-GLOBULE-MEMBRANE; MAMMARY EPITHELIAL-CELLS; DIFFERENTIATION-RELATED
PROTEIN; BOVINE-MILK; XANTHINE-OXIDOREDUCTASE; APICAL MEMBRANE;
BUTYROPHILIN; GLAND; GLYCOPROTEIN; LACTATION
AB Milk lipid is secreted by a unique process, during which triacylglycerol droplets bud from mammary cells coated with an outer bilayer of apical membrane. In all current schemes, the integral protein butyrophilin 1A1 (B ) is postulated to serve as a transmembrane scaffold, which interacts either with itself or with the peripheral proteins, xanthine oxidoreductase (XOR) and possibly perilipin-2 (PLIN2), to form an immobile bridging complex between the droplet and apical surface. In one such scheme, B on the surface of cytoplasmic lipid droplets interacts directly with B in the apical membrane without binding to either XOR or PLIN2. We tested these models using both biochemical and morphological approaches. B was concentrated in the apical membrane in all species examined and contained mature N-linked glycans. We found no evidence for the association of unprocessed B with intracellular lipid droplets. B -enhanced green fluorescent protein was highly mobile in areas of mouse milk-lipid droplets that had not undergone post-secretion changes, and endogenous mouse B comprised only 0.5-0.7% (w/w) of the total protein, i.e. over 50-fold less than in the milk-lipid droplets of cow and other species. B is the major component of an immobile global adhesive complex and suggest that interactions between B and other proteins at the time of secretion are more transient than previously predicted. B in lipid droplets marks it as a potential mobile signaling molecule in milk.
C1 [Jeong, Jaekwang; Lisinski, Ivonne; Kadegowda, Anil K. G.; Shin, Hyunsu; Mather, Ian H.] Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA.
[Wooding, F. B. Peter] Univ Cambridge, Physiol Lab, Cambridge CB2 3EG, England.
[Daniels, Brian R.] NICHHD, Bethesda, MD 20892 USA.
[Schaack, Jerome] Univ Colorado, Denver Sch Med, Dept Microbiol, Aurora, CO 80045 USA.
RP Mather, IH (reprint author), Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA.
EM imather@umd.edu
FU USDA NRI Program [2005-04637]; NICHD-NIH [1R01 HD048588-01A1]; Maryland
Agricultural Experiment Station
FX We thank Tim Reardon and Liane West for animal care and maintenance and
Dr Dale Hailey (University of Washington, Seattle, WA) for Clontech
vectors. Dr Roberto Weigert (IMTU, NIDCR, National Institutes of Health,
Bethesda, MD) provided access to the Olympus confocal microscope and
Imaris software. This work was funded by grants from the USDA NRI
Program (2005-04637), NICHD-NIH (1R01 HD048588-01A1) and the Maryland
Agricultural Experiment Station to I. H. M. None of the authors have
conflicts of interest to declare.
NR 58
TC 11
Z9 11
U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-9219
J9 TRAFFIC
JI Traffic
PD SEP
PY 2013
VL 14
IS 9
BP 974
EP 986
DI 10.1111/tra.12087
PG 13
WC Cell Biology
SC Cell Biology
GA 195SB
UT WOS:000322722800003
PM 23738536
ER
PT J
AU Ghirlando, R
Balbo, A
Piszczek, G
Brown, PH
Lewis, MS
Brautigam, CA
Schuck, P
Zhao, HY
AF Ghirlando, Rodolfo
Balbo, Andrea
Piszczek, Grzegorz
Brown, Patrick H.
Lewis, Marc S.
Brautigam, Chad A.
Schuck, Peter
Zhao, Huaying
TI Improving the thermal, radial, and temporal accuracy of the analytical
ultracentrifuge through external references
SO ANALYTICAL BIOCHEMISTRY
LA English
DT Article
DE Sedimentation velocity; Sedimentation equilibrium; Hydrodynamic modeling
ID VELOCITY ANALYTICAL ULTRACENTRIFUGATION; PROTEIN-PROTEIN INTERACTIONS;
SEDIMENTATION-VELOCITY; LAMM EQUATION; TEMPERATURE-MEASUREMENT;
COMPUTER; EQUILIBRIUM; THERMOMETER; DISTRIBUTIONS; CONFORMATION
AB Sedimentation velocity (SV) is a method based on first principles that provides a precise hydrodynamic characterization of macromolecules in solution. Due to recent improvements in data analysis, the accuracy of experimental SV data emerges as a limiting factor in its interpretation. Our goal was to unravel the sources of experimental error and develop improved calibration procedures. We implemented the use of a Thermochron iButton temperature logger to directly measure the temperature of a spinning rotor and detected deviations that can translate into an error of as much as 10% in the sedimentation coefficient. We further designed a precision mask with equidistant markers to correct for instrumental errors in the radial calibration that were observed to span a range of 8.6%. The need for an independent time calibration emerged with use of the current data acquisition software (Zhao et al., Anal. Biochem., 437 (2013) 104-108), and we now show that smaller but significant time errors of up to 2% also occur with earlier versions. After application of these calibration corrections, the sedimentation coefficients obtained from 11 instruments displayed a significantly reduced standard deviation of approximately 0.7%. This study demonstrates the need for external calibration procedures and regular control experiments with a sedimentation coefficient standard. Published by Elsevier Inc.
C1 [Ghirlando, Rodolfo] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Balbo, Andrea; Brown, Patrick H.; Lewis, Marc S.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA.
[Piszczek, Grzegorz] NHLBI, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA.
[Brautigam, Chad A.] Univ Texas SW Med Ctr Dallas, Dept Biophys, Dallas, TX 75390 USA.
[Schuck, Peter; Zhao, Huaying] Natl Inst Biomed Imaging & Bioengn, Dynam Macromol Assembly Sect, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA.
RP Schuck, P (reprint author), Natl Inst Biomed Imaging & Bioengn, Dynam Macromol Assembly Sect, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA.
EM schuckp@mail.nih.gov; zhaoh3@mail.nih.gov
OI Schuck, Peter/0000-0002-8859-6966
FU Intramural Research Programs of the National Institute of Biomedical
Imaging and Bioengineering; National Institute of Diabetes and Digestive
and Kidney Diseases; National Heart, Lung, and Blood Institute, National
Institutes of Health
FX We thank Erby Perdue for his expert advice and for taking excellent care
of our analytical ultracentrifuges and thank Dr. Nicole Morgan for
helpful discussions. This work was supported by the Intramural Research
Programs of the National Institute of Biomedical Imaging and
Bioengineering, the National Institute of Diabetes and Digestive and
Kidney Diseases, and the National Heart, Lung, and Blood Institute,
National Institutes of Health.
NR 71
TC 21
Z9 21
U1 1
U2 15
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0003-2697
J9 ANAL BIOCHEM
JI Anal. Biochem.
PD SEP 1
PY 2013
VL 440
IS 1
BP 81
EP 95
DI 10.1016/j.ab.2013.05.011
PG 15
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 191MP
UT WOS:000322417500015
PM 23711724
ER
PT J
AU Yan, PK
Zhang, WX
Turkbey, B
Choyke, PL
Li, XL
AF Yan, Pingkun
Zhang, Wuxia
Turkbey, Baris
Choyke, Peter L.
Li, Xuelong
TI Global structure constrained local shape prior estimation for medical
image segmentation
SO COMPUTER VISION AND IMAGE UNDERSTANDING
LA English
DT Article
DE Target-oriented shape modeling; Manifold learning; Manifold assumption;
Medical image segmentation
ID DIMENSIONALITY REDUCTION; MODELS; OBJECTS; SPACE; MRI
AB Organ shape plays an important role in clinical diagnosis, surgical planning and treatment evaluation. Shape modeling is a critical factor affecting the performance of deformable model based segmentation methods for organ shape extraction. In most existing works, shape modeling is completed in the original shape space, with the presence of outliers. In addition, the specificity of the patient was not taken into account. This paper proposes a novel target-oriented shape prior model to deal with these two problems in a unified framework. The proposed method measures the intrinsic similarity between the target shape and the training shapes on an embedded manifold by manifold learning techniques. With this approach, shapes in the training set can be selected according to their intrinsic similarity to the target image. With more accurate shape guidance, an optimized search is performed by a deformable model to minimize an energy functional for image segmentation, which is efficiently achieved by using dynamic programming. Our method has been validated on 2D prostate localization and 3D prostate segmentation in MRI scans. Compared to other existing methods, our proposed method exhibits better performance in both studies. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Yan, Pingkun; Zhang, Wuxia; Li, Xuelong] Chinese Acad Sci, Ctr OPT IMagery Anal & Learning OPTIMAL, State Key Lab Transient Opt & Photon, Xian Inst Opt & Precis Mech, Xian 710119, Shaanxi, Peoples R China.
[Turkbey, Baris; Choyke, Peter L.] NCI, NIH, Bethesda, MD 20892 USA.
RP Yan, PK (reprint author), Chinese Acad Sci, Ctr OPT IMagery Anal & Learning OPTIMAL, State Key Lab Transient Opt & Photon, Xian Inst Opt & Precis Mech, Xian 710119, Shaanxi, Peoples R China.
EM pingkun@ieee.org
FU National Basic Research Program of China (973 Program) [2012CB719905];
National Natural Science Foundation of China [61125106, 61172142,
91120302, 61072093]
FX This work is supported by the National Basic Research Program of China
(973 Program) (Grant No. 2012CB719905) and by the National Natural
Science Foundation of China (Grant Nos: 61125106, 61172142, 91120302,
and 61072093).
NR 34
TC 8
Z9 9
U1 1
U2 21
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1077-3142
J9 COMPUT VIS IMAGE UND
JI Comput. Vis. Image Underst.
PD SEP
PY 2013
VL 117
IS 9
BP 1017
EP 1026
DI 10.1016/j.cviu.2013.03.006
PG 10
WC Computer Science, Artificial Intelligence; Engineering, Electrical &
Electronic
SC Computer Science; Engineering
GA 182EK
UT WOS:000321724300005
ER
PT J
AU Ma, J
Lu, L
AF Ma, Jun
Lu, Le
TI Hierarchical segmentation and identification of thoracic vertebra using
learning-based edge detection and coarse-to-fine deformable model
SO COMPUTER VISION AND IMAGE UNDERSTANDING
LA English
DT Article
DE Supervised edge detection; Coarse-to-fine shape deformation model; Shape
based medical image segmentation; Vertebra segmentation; Vertebra
identification; Computed tomography
ID IMAGES; FEATURES; NODULES; SPINE
AB Precise segmentation and identification of thoracic vertebrae is important for many medical imaging applications though it remains challenging due to the vertebra's complex shape and varied neighboring structures. In this paper, a new method based on learned bone-structure edge detectors and a coarse-to-fine deformable surface model is proposed to segment and identify vertebrae in 3D CT thoracic images. In the training stage, a discriminative classifier for object-specific edge detection is trained using steerable features and statistical shape models for 12 thoracic vertebrae are also learned. For the run-time testing, we design a new coarse-to-fine, two-stage segmentation strategy: subregions of a vertebra first deform together as a group; then vertebra mesh vertices in a smaller neighborhood move group-wise to progressively drive the deformable model towards edge response maps by optimizing a probability cost function. In this manner, the smoothness and topology of vertebrae shapes are guaranteed. This algorithm performs successfully with reliable mean point-to-surface errors 0.95 +/- 0.91 mm on 40 volumes. Consequently a vertebra identification scheme is also proposed via mean surface mesh matching. We achieve a success rate of 73.1% using a single vertebra, and over 95% for 8 or more vertebra which is comparable or slightly better than state-of-the-art [5]. Published by Elsevier Inc.
C1 Siemens Mol Imaging, Hoffman Estates, IL 60192 USA.
Siemens Corp Res, Princeton, NJ 08540 USA.
RP Lu, L (reprint author), NIH, Ctr Clin, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM jun.jm.ma@siemens.com; le.lu@nih.gov
NR 30
TC 16
Z9 17
U1 0
U2 21
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1077-3142
EI 1090-235X
J9 COMPUT VIS IMAGE UND
JI Comput. Vis. Image Underst.
PD SEP
PY 2013
VL 117
IS 9
BP 1072
EP 1083
DI 10.1016/j.cviu.2012.11.016
PG 12
WC Computer Science, Artificial Intelligence; Engineering, Electrical &
Electronic
SC Computer Science; Engineering
GA 182EK
UT WOS:000321724300010
ER
PT J
AU Chang, YJ
Chen, HC
Pan, MH
Lee, BH
You, SL
Lin, CY
Chou, YC
Hsieh, CY
Cheng, YJ
Liaw, KL
Hsing, AW
Schiffman, M
Chen, CJ
AF Chang, Ya-Ju
Chen, Hui-Chi
Pan, Mei-Hung
Lee, Bor-Heng
You, San-Lin
Lin, Ching-Yu
Chou, Yi-Chun
Hsieh, Chang-Yao
Cheng, Yu-Juen
Liaw, Kai-Li
Hsing, Ann W.
Schiffman, Mark
Chen, Chien-Jen
CA CBCSP-HPV Study Grp
TI Intratypic variants of human papillomavirus type 16 and risk of cervical
Neoplasia in Taiwan
SO JOURNAL OF MEDICAL VIROLOGY
LA English
DT Article
DE HPV 16; variants; prevalence; cervical neoplasia; Taiwan
ID 16 E6 VARIANTS; INTRAEPITHELIAL NEOPLASIA; HPV16 E6; SEQUENCE VARIANTS;
NATURAL VARIANTS; GENOTYPING ARRAY; KOREAN WOMEN; CANCER;
HUMAN-PAPILLOMAVIRUS-16; LESIONS
AB The associations between variants of human papillomavirus (HPV) 16 and risk of cervical neoplasia have been reported, but nucleotide variations of HPV 16 in Asian populations and their association with cervical neoplasia have not been evaluated extensively. During 1991-1992, 11,923 women from seven townships in Taiwan were enrolled. The HPV DNA in cervical cells was detected and genotyped using EasyChip HPV blot. Nucleotide variations in the long control region (LCR), E6, and E7 genes were determined using DNA sequencing for 170 HPV 16-positive cervical samples. The Asian variant was the most prevalent variant (81.8%) of HPV 16 in Taiwan, and was also associated with increased prevalence of histologically confirmed cervical intraepithelial neoplasia grade 3 or worse, showing an age-adjusted odds ratio (exact confidence limits) of 10.70 (1.62-451.05; P=0.0049) compared to the HPV 16 European variant. Similar significant associations with cervical intraepithelial neoplasia grade 3 or worse were also observed for distinct nucleotide substitutions, including T178A/G, A647G, A7730C/G, T7781C, G7842A, and C24T/G. These results demonstrate that non-European variants (non-E) of HPV 16, predominantly Asian variants, are associated with increased risk for severe cervical neoplasia, compared with European variants. Molecular mechanisms accounting for varied cervical neoplasia risk among different HPV 16 variants warrant further investigation. J. Med. Virol. 85:1567-1576, 2013. (c) 2013 Wiley Periodicals, Inc.
C1 [Chang, Ya-Ju; Chou, Yi-Chun; Cheng, Yu-Juen; Chen, Chien-Jen] Natl Taiwan Univ, Grad Inst Epidemiol, Taipei 10764, Taiwan.
[Chen, Hui-Chi; Pan, Mei-Hung; You, San-Lin; Chen, Chien-Jen] Acad Sinica, Genom Res Ctr, Taipei 11529, Taiwan.
[Lee, Bor-Heng] King Car Food Ind Co Ltd, Yuan Shan Res Inst, Ilan, Taiwan.
[Lin, Ching-Yu] Taipei Med Univ, Sch Med Lab Sci & Biotechnol, Taipei, Taiwan.
[Hsieh, Chang-Yao] Natl Taiwan Univ Hosp, Dept Obstet & Gynecol, Taipei, Taiwan.
[Hsing, Ann W.; Schiffman, Mark] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Chen, CJ (reprint author), Acad Sinica, Genom Res Ctr, 128 Acad Rd Sect 2, Taipei 11529, Taiwan.
EM chencj@gate.sinica.edu.tw
RI Chen, Chien-Jen/C-6976-2008;
OI Lin, Ching-Yu/0000-0001-8269-797X
FU National Science Council [94-2314-B-001-011, 95-2314-B-001-007,
96-2314-B-001-004, 97-2314-B-001-001-MY3]
FX Grant sponsor: National Science Council; Grant numbers:
94-2314-B-001-011; 95-2314-B-001-007; 96-2314-B-001-004;
97-2314-B-001-001-MY3.
NR 44
TC 8
Z9 8
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0146-6615
J9 J MED VIROL
JI J. Med. Virol.
PD SEP
PY 2013
VL 85
IS 9
BP 1567
EP 1576
DI 10.1002/jmv.23651
PG 10
WC Virology
SC Virology
GA 181WD
UT WOS:000321699700011
PM 23852681
ER
PT J
AU Shebl, FM
Emmanuel, B
Bunts, L
Biryahwaho, B
Kiruthu, C
Huang, ML
Pfeiffer, RM
Casper, C
Mbulaiteye, SM
AF Shebl, Fatma M.
Emmanuel, Benjamin
Bunts, Lisa
Biryahwaho, Benon
Kiruthu, Christine
Huang, Meei-Li
Pfeiffer, Ruth M.
Casper, Corey
Mbulaiteye, Sam M.
TI Population-based assessment of kaposi sarcoma-associated herpesvirus DNA
in plasma among Ugandans
SO JOURNAL OF MEDICAL VIROLOGY
LA English
DT Article
DE Kaposi sarcoma-associated herpesvirus; *Kaposi sarcoma; plasma;
epidemiology; uganda
ID HUMAN-HERPESVIRUS-8 INFECTION; RISK-FACTORS; SEROLOGIC ASSAYS;
HOMOSEXUAL MEN; HIV-INFECTION; EAST-AFRICA; TRANSMISSION; CANCER;
ADULTS; SEROPREVALENCE
AB Risk of Kaposi sarcoma (KS) is linked to detection of Kaposi sarcoma-associated herpesvirus (KSHV) DNA in plasma, but little is known about the prevalence and risk factors for plasma KSHV DNA detection among the general population where KS is endemic. Correlates of KSHV plasma detection were investigated in a population-based sample of adult Ugandans (15-59 years) who participated in an HIV/AIDS serobehavioral survey in 2004/2005. KSHV DNA was measured in plasma of 1,080 KSHV seropositive and 356 KSHV seronegative persons using polymerase chain reaction (PCR). KSHV DNA in plasma was detected in 157 (8.7%) persons; of these 149 (95%) were KSHV seropositive and 8 (5%) were seronegative. Detection of KSHV DNA in plasma was significantly associated with male sex (P<0.001), older age (P=0.003), residence in a rural versus urban area (P=0.002), geographic region (P=0.02), and being KSHV seropositive (13.8% seropositive vs. 2.3% seronegative, P<0.001). In a multivariable model, KSHV DNA plasma quantity was significantly higher in men (P=0.002), inversely associated with age (P=0.05), and residing in an urban area (P=0.01). In Uganda, KSHV is detected more frequently in the plasma of adult males and residents of rural regions, potentially explaining the increased risk of KS in these subsets of the Ugandan population. J. Med. Virol. 85:1602-1610, 2013. (c) 2013 Wiley Periodicals, Inc.
C1 [Shebl, Fatma M.] Yale Univ, Sch Publ Hlth, New Haven, CT USA.
[Emmanuel, Benjamin; Kiruthu, Christine; Pfeiffer, Ruth M.; Mbulaiteye, Sam M.] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
[Bunts, Lisa; Casper, Corey] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Publ Hlth Sci & Clin Res Div, Seattle, WA 98104 USA.
[Biryahwaho, Benon] Uganda Virus Res Inst, Entebbe, Uganda.
[Huang, Meei-Li] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA.
[Casper, Corey] Univ Washington, Dept Med, Seattle, WA USA.
[Casper, Corey] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Casper, Corey] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA.
RP Mbulaiteye, SM (reprint author), 6120 Execut Blvd,Execut Plaza South,Rm 7080,MSC 7, Rockville, MD 20852 USA.
EM mbulaits@mail.nih.gov
FU Intramural NIH HHS [ZIA CP010176-12]
NR 39
TC 5
Z9 5
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0146-6615
J9 J MED VIROL
JI J. Med. Virol.
PD SEP
PY 2013
VL 85
IS 9
BP 1602
EP 1610
DI 10.1002/jmv.23613
PG 9
WC Virology
SC Virology
GA 181WD
UT WOS:000321699700016
PM 23852686
ER
PT J
AU Chauchard, E
Levin, KH
Copersino, ML
Heishman, SJ
Gorelick, DA
AF Chauchard, Emeline
Levin, Kenneth H.
Copersino, Marc L.
Heishman, Stephen J.
Gorelick, David A.
TI Motivations to quit cannabis use in an adult non-treatment sample: Are
they related to relapse?
SO ADDICTIVE BEHAVIORS
LA English
DT Article
DE Cannabis; Motivation to quit; Cessation; Relapse
ID EXTRINSIC MOTIVATION; MARIJUANA USE; SMOKING-CESSATION; REASONS;
SMOKERS; POPULATION; REMISSIONS; WITHDRAWAL; PATHWAY; COCAINE
AB Background: The majority of cannabis smokers who quit do so without formal treatment, suggesting that motivations to quit are an important part of cessation process. However, little is known about how motivations relate to successful quitting.
Method: A convenience sample of 385 non-treatment-seeking adult cannabis smokers (58% male, age 16-64 years at start of quit attempt) who made a "serious" (self-defined) quit attempt without formal treatment while not in a controlled environment were administered the 176-item Marijuana Quit Questionnaire (MJQQ) to assess their motivations to quit and outcome of the quit attempt Exploratory factor analysis was performed to identify significant motivational factors. Subgroup comparisons used t-tests and ANOVA. Cox proportional hazard regression and the General Linear Model were performed to evaluate the influence of motivational factors, gender, and age on relapse status at time of interview and risk of relapse over time, with time between quit attempt and interview as a covariate.
Results: Exploratory factor analysis identified 6 motivational factors with eigenvalues >1 which accounted for 58.4% of the total variance: self-image and self-control, health concerns, interpersonal relationship concerns, legal concerns, social acceptability concerns, and self-efficacy. Women were more likely than men to be motivated by self-image/self-control, health concerns, and social acceptability concerns. Older individuals were more likely to be motivated by health concerns. At the time of interview, 339 subjects had relapsed. Self-image and self-control, health concerns, interpersonal relationship concerns, and social acceptability concerns were associated with greater likelihood of abstinence at the study interview. Legal concerns and social acceptability concerns were associated with significantly lower hazard ratios (0.88, 0.83) for relapse during the abstinent period.
Conclusion: These findings show gender and age differences in motivations to quit cannabis smoking and that adult cannabis smokers have motivations to quite similar to those of adolescent cannabis smokers and of adults who quit alcohol and tobacco use without formal treatment. The findings suggest areas of focus to improve secondary prevention and psychosocial treatment efforts. Published by Elsevier Ltd.
C1 [Chauchard, Emeline; Levin, Kenneth H.; Heishman, Stephen J.; Gorelick, David A.] NIDA, Intramural Res Program, Baltimore, MD 21224 USA.
[Chauchard, Emeline] Univ Toulouse, Lab Octogone CERPP, F-31058 Toulouse 9, France.
[Copersino, Marc L.] Harvard Univ, Sch Med, McLean Hosp, Belmont, MA 02478 USA.
RP Gorelick, DA (reprint author), NIDA, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA.
EM emeline.chauchard@gmail.com; khlevin@gmail.com;
mcopersino@mclean.harvard.edu; sheish@intra.nida.nih.gov;
dgorelic@intra.nida.nih.gov
FU NIH, National Institute on Drug Abuse; joint action of the
Interministerial Mission for the Fight against Drugs and Drug Addiction
(MILDT, French Government); University of Toulouse II, Le Mirail
FX Funding for this study was provided by the Intramural Research Program,
NIH, National Institute on Drug Abuse. Dr. Chauchard received funding
from the joint action of the Interministerial Mission for the Fight
against Drugs and Drug Addiction (MILDT, French Government) and the
University of Toulouse II, Le Mirail. Neither NIH, MILDT, nor the
University of Toulouse played any role in study design; in the
collection, analysis, and interpretation of data; in the writing of the
report; or in the decision to submit the paper for publication.
NR 34
TC 10
Z9 10
U1 3
U2 24
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4603
J9 ADDICT BEHAV
JI Addict. Behav.
PD SEP
PY 2013
VL 38
IS 9
BP 2422
EP 2427
DI 10.1016/j.addbeh.2013.04.002
PG 6
WC Psychology, Clinical; Substance Abuse
SC Psychology; Substance Abuse
GA 179SE
UT WOS:000321540800002
PM 23685328
ER
PT J
AU Ranzenhofer, LM
Hannallah, L
Field, SE
Shomaker, LB
Stephens, M
Sbrocco, T
Kozlosky, M
Reynolds, J
Yanovski, JA
Tanofsky-Kraff, M
AF Ranzenhofer, Lisa M.
Hannallah, Louise
Field, Sara E.
Shomaker, Lauren B.
Stephens, Mark
Sbrocco, Tracy
Kozlosky, Merel
Reynolds, James
Yanovski, Jack A.
Tanofsky-Kraff, Marian
TI Pre-meal affective state and laboratory test meal intake in adolescent
girls with loss of control eating
SO APPETITE
LA English
DT Article
DE Adolescence; Loss of control eating; Negative affect; Binge eating
ID ECOLOGICAL MOMENTARY ASSESSMENT; CONSTRUCT-VALIDITY; FOOD SELECTION;
ADULT OBESITY; HIGH-RISK; BODY-FAT; BINGE; CHILDREN; DISORDER;
OVERWEIGHT
AB Loss of control eating confers risk for excess weight gain and exacerbated disordered eating. Affect theory proposes that loss of control eating is used to cope with negative mood states. Self-report data suggest that negative affect may contribute to the etiology of loss of control eating, but this theory has not been well-tested using laboratory paradigms. We examined associations between pre-meal affective states and intake during a laboratory test meal. One-hundred and ten adolescent girls with reported loss of control eating whose body mass index fell between the 75th and 97th percentile for age and sex completed state mood ratings prior to a test-meal. Results indicated that pre-meal state negative affect was associated with greater carbohydrate and less protein consumption, as well as greater snack and dessert and less fruit and dairy intake. All girls experienced significant decreases in negative affect from pre- to post-meal, but intake during the meal was unassociated with post-meal affect. In support of affect theory, negative affective states reported among girls with loss of control may be a driving factor for increased energy-dense food intake, which may play a role in excess weight gain. Published by Elsevier Ltd.
C1 [Ranzenhofer, Lisa M.; Hannallah, Louise; Field, Sara E.; Shomaker, Lauren B.; Sbrocco, Tracy; Yanovski, Jack A.; Tanofsky-Kraff, Marian] USUHS, Dept Med & Clin Psychol, Bethesda, MD 20814 USA.
[Ranzenhofer, Lisa M.; Hannallah, Louise; Field, Sara E.; Shomaker, Lauren B.; Tanofsky-Kraff, Marian] Eunice Kennedy Shriyer Natl Inst Child Hlth & Hum, Sect Growth & Obes, Program Dev Endocrinol & Genet, NIH,DHHS, Bethesda, MD 20892 USA.
[Stephens, Mark] USUHS, Dept Family Med, Bethesda, MD 20814 USA.
[Kozlosky, Merel] NIH, Dept Nutr, Ctr Clin, DHHS, Bethesda, MD 20892 USA.
[Reynolds, James] NIH, Dept Nucl Med, Hatfield Clin Res Ctr, DHHS, Bethesda, MD 20892 USA.
RP Tanofsky-Kraff, M (reprint author), USUHS, Dept Med & Clin Psychol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM marian.tanofsky-kraff@usuhs.edu
RI Stephens, Mark/A-2679-2015;
OI Yanovski, Jack/0000-0001-8542-1637
FU NIDDK [1R01DK080906-01A1]; USUHS Grant [R072IC]; NICHD Intramural
Research Program [ZIA-HO-00641]
FX NIDDK Grant 1R01DK080906-01A1 (to MTK), USUHS Grant R072IC (to MTK) and
NICHD Intramural Research Program ZIA-HO-00641 (to JAY). J. Yanovski and
M. Kozlosky are commissioned officers in the U.S. Public Health Service
(PHS). M. Stephens is active duty in the US Navy. Disclaimer: The
opinions and assertions expressed herein are those of the authors and
are not to be construed as reflecting the views of the PHS, the
Department of the Navy, USUHS or the U.S. Department of Defense.
NR 55
TC 13
Z9 13
U1 0
U2 25
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0195-6663
J9 APPETITE
JI Appetite
PD SEP 1
PY 2013
VL 68
BP 30
EP 37
DI 10.1016/j.appet.2013.03.018
PG 8
WC Behavioral Sciences; Nutrition & Dietetics
SC Behavioral Sciences; Nutrition & Dietetics
GA 178TI
UT WOS:000321469900005
PM 23603224
ER
PT J
AU Castilho, RM
Squarize, CH
Gutkind, JS
AF Castilho, R. M.
Squarize, C. H.
Gutkind, J. S.
TI Exploiting PI3K/mTOR signaling to accelerate epithelial wound healing
SO ORAL DISEASES
LA English
DT Review
DE PTEN; TSC1/TSC2; AKT; oral wound; wound therapy
ID PROTEIN-KINASE-B; HAIR FOLLICLE; STEM-CELLS; TUMOR-SUPPRESSOR;
PHOSPHOINOSITIDE 3-KINASE; SKIN; PTEN; PERIOSTIN; EPIDERMIS;
DIFFERENTIATION
AB The molecular circuitries controlling the process of skin wound healing have gained new significant insights in recent years. This knowledge is built on landmark studies on skin embryogenesis, maturation, and differentiation. Furthermore, the identification, characterization, and elucidation of the biological roles of adult skin epithelial stem cells and their influence in tissue homeostasis have provided the foundation for the overall understanding of the process of skin wound healing and tissue repair. Among numerous signaling pathways associated with epithelial functions, the PI3K/Akt/mTOR signaling route has gained substantial attention with the generation of animal models capable of dissecting individual components of the pathway, thereby providing a novel insight into the molecular framework underlying skin homeostasis and tissue regeneration. In this review, we focus on recent findings regarding the mechanisms involved in wound healing associated with the upregulation of the activity of the PI3K/Akt/mTOR circuitry. This review highlights critical findings on the molecular mechanisms controlling the activation of mTOR, a downstream component of the PI3K-PTEN pathway, which is directly involved in epithelial migration and proliferation. We discuss how this emerging information can be exploited for the development of novel pharmacological intervention strategies to accelerate the healing of critical size wounds.
C1 [Castilho, R. M.; Squarize, C. H.] Univ Michigan, Lab Epithelial Biol, Dept Periodont & Oral Med, Sch Dent, Ann Arbor, MI 48109 USA.
[Gutkind, J. S.] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA.
RP Castilho, RM (reprint author), Univ Michigan, Lab Epithelial Biol, Dept Periodont & Oral Med, 1011 N Univ Ave,Room 3323B, Ann Arbor, MI 48109 USA.
EM rcastilh@umich.edu
FU National Institutes of Health (NIH/NCI) [P50-CA97248]; Intramural
Research Program of the US National Institutes of Health (NIH); National
Institute of Dental and Craniofacial Research (NIDCR)
FX The authors are supported by the National Institutes of Health (NIH/NCI)
P50-CA97248 (University of Michigan Head and Neck SPORE) and by the
Intramural Research Program of the US National Institutes of Health
(NIH) and National Institute of Dental and Craniofacial Research
(NIDCR).
NR 56
TC 13
Z9 16
U1 1
U2 23
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1354-523X
J9 ORAL DIS
JI Oral Dis.
PD SEP
PY 2013
VL 19
IS 6
BP 551
EP 558
DI 10.1111/odi.12070
PG 8
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 179KH
UT WOS:000321518700002
PM 23379329
ER
PT J
AU Warren, KE
Poussaint, TY
Vezina, G
Hargrave, D
Packer, RJ
Goldman, S
Wen, PY
Pollack, IF
Zurakowski, D
Kun, LE
Prados, MD
Rutkowski, S
Kieran, MW
AF Warren, Katherine E.
Poussaint, Tina Y.
Vezina, Gilbert
Hargrave, Darren
Packer, Roger J.
Goldman, Stewart
Wen, Patrick Y.
Pollack, Ian F.
Zurakowski, David
Kun, Larry E.
Prados, Michael D.
Rutkowski, Stefan
Kieran, Mark W.
TI Challenges with defining response to antitumor agents in pediatric
neuro-oncology: A report from the response assessment in pediatric
neuro-oncology (RAPNO) working group
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE brain; imaging; pediatric; RANO; response; tumor
ID INTRINSIC PONTINE GLIOMAS; HIGH-GRADE GLIOMAS; INTEROBSERVER
VARIABILITY; CHEMOTHERAPY; CHILDREN; CRITERIA; CARBOPLATIN; ONCOLOGY;
SURVIVAL; THERAPY
AB Criteria for new drug approval include demonstration of efficacy. In neuro-oncology, this is determined radiographically utilizing tumor measurements on MRI scans. Limitations of this method have been identified where drug activity is not reflected in decreased tumor size. The RANO (Response Assessment in Neuro-Oncology) working group was established to address limitations in defining endpoints for clinical trials in adult neuro-oncology and to develop standardized response criteria. RAPNO was subsequently established to address unique issues in pediatric neuro-oncology. The aim of this paper is to delineate response criteria issues in pediatric clinical trials as a basis for subsequent recommendations. Pediatr Blood Cancer 2013;60:1397-1401. (c) 2013 Wiley Periodicals, Inc.
C1 [Warren, Katherine E.] NCI, Bethesda, MD 20892 USA.
[Poussaint, Tina Y.; Zurakowski, David] Childrens Hosp, Boston, MA 02115 USA.
[Vezina, Gilbert; Packer, Roger J.] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Hargrave, Darren] Great Ormond St Hosp Sick Children, London WC1N 3JH, England.
[Goldman, Stewart] Lurie Childrens Hosp Chicago, Chicago, IL USA.
[Wen, Patrick Y.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Pollack, Ian F.] Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA.
[Kun, Larry E.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA.
[Prados, Michael D.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Rutkowski, Stefan] Univ Med Ctr, Hamburg, Germany.
[Kieran, Mark W.] Dana Farber Childrens Hosp Canc Ctr, Boston, MA USA.
RP Warren, KE (reprint author), NCI, Pediat Oncol Branch, Bldg 10 Room 1-5750,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM warrenk@mail.nih.gov
RI Hargrave, Darren/H-1066-2014;
OI Hargrave, Darren/0000-0001-8219-9807; Kieran, Mark/0000-0003-2184-7692
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research
FX Grant sponsor: Intramural Research Program of the National Institutes of
Health, National Cancer Institute, Center for Cancer Research
NR 25
TC 16
Z9 16
U1 0
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD SEP
PY 2013
VL 60
IS 9
BP 1397
EP 1401
DI 10.1002/pbc.24562
PG 5
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 181XM
UT WOS:000321703900068
PM 23625747
ER
PT J
AU Skapek, SX
Anderson, J
Barr, FG
Bridge, J
Gastier-Foster, JM
Parham, DM
Rudzinski, ER
Triche, T
Hawkins, DS
AF Skapek, Stephen X.
Anderson, James
Barr, Frederic G.
Bridge, JuliaA.
Gastier-Foster, Julie M.
Parham, David M.
Rudzinski, Erin R.
Triche, Timothy
Hawkins, Douglas S.
TI PAX-FOXO1 fusion status drives unfavorable outcome for children with
rhabdomyosarcoma: A children's oncology group report
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE PAX-FOXO1; rhabdomyosarcoma; survival
ID NEGATIVE ALVEOLAR RHABDOMYOSARCOMA; GENE-EXPRESSION; RISK
STRATIFICATION; PAX3; TRANSLOCATION; SARCOMAS; FKHR
AB Background. Rhabdomyosarcoma (RMS) is divided into two major histological subtypes: alveolar (ARMS) and embryonal (ERMS), with most ARMS expressing one of two oncogenic genes fusing PAX3 or PAX7 with FOXO1 (P3F and P7F, respectively). The Children's Oncology Group (COG) carried out a multi-institutional clinical trial to evaluate the prognostic value of PAX-FOXO1 fusion status. Methods. Study participants were treated on COG protocol D9803 for intermediate risk ARMS or ERMS using multi-agent chemotherapy, radiotherapy, and surgery. Central diagnostic pathology review and molecular testing for fusion genes were carried out on prospectively collected specimens. Event-free (EFS) and overall survival (OS) at 5 years were correlated with histological subtype and PAX-FOXO1 status. Results. Of 616 eligible D9803 enrollees, 434 cases had adequate clinical, molecular, and pathology data for definitive classification as ERMS, ARMS P3F+ or P7F+, or ARMSn (without detectable fusion). EFS was worse for those with ARMS P3F+ (54%) and P7F+ (65%) than those with ERMS (77%; P < 0.001). EFS for ARMSn and ERMS were not statistically different (90% vs. 77%, P = 0.15). ARMS P3F+ had poorer OS (64%) than ARMS P7F+(87%), ARMSn (89%), and ERMS (82%; P=0.006). Conclusions. ARMSn has an outcome similar to ERMS and superior EFS compared to ARMS with either P3F or P7F, when given therapy designed for children with intermediate risk RMS. This prospective analysis supports incorporation of PAX-FOXO1 fusion status into risk stratification and treatment allocation. Pediatr Blood Cancer 2013;60:1411-1417. (C) 2013 Wiley Periodicals, Inc.
C1 [Skapek, Stephen X.] Childrens Med Ctr, Dallas, TX 75235 USA.
[Skapek, Stephen X.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Anderson, James; Bridge, JuliaA.] Univ Nebraska Med Ctr, Omaha, NE USA.
[Barr, Frederic G.] NCI, Bethesda, MD 20892 USA.
[Gastier-Foster, Julie M.] Ohio State Univ, Nationwide Childrens Hosp, Columbus, OH 43210 USA.
[Parham, David M.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA.
[Rudzinski, Erin R.] Seattle Childrens Hosp, Seattle, WA USA.
[Triche, Timothy] Univ So Calif, Childrens Hosp Los Angeles, Los Angeles, CA USA.
[Hawkins, Douglas S.] Seattle Childrens Hosp, Fred Hutchinson Canc Res Ctr, Seattle, WA USA.
[Hawkins, Douglas S.] Univ Washington, Seattle, WA 98195 USA.
RP Skapek, SX (reprint author), Univ Texas SW Med Ctr Dallas, Dept Pediat, Ctr Canc & Blood Disorders, Childrens Med Ctr, 5323 Harry Hines Blvd,MC 9063, Dallas, TX 75390 USA.
EM stephen.skapek@utsouthwestern.edu
FU St. Baldrick's Foundation [179772]; NIH [CA148216, CA104896 CA098413]
FX Grant sponsor: St. Baldrick's Foundation; Grant number: #179772; Grant
sponsor: NIH; Grant numbers: CA148216; CA104896 CA098413.
NR 27
TC 42
Z9 44
U1 0
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD SEP
PY 2013
VL 60
IS 9
BP 1411
EP 1417
DI 10.1002/pbc.24532
PG 7
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 181XM
UT WOS:000321703900071
PM 23526739
ER
PT J
AU Bode, SFN
Jessen, B
Ammann, S
Maul-Pavicic, A
de Saint Basile, G
Janka, G
Lehmberg, K
zur Stadt, U
Gochuico, BR
Gahl, WA
Klein, C
Diestelhorst, J
Griese, M
Frei-Jones, MJ
Pace, D
Davies, G
Schwarz, K
Griffiths, G
Ehl, S
AF Bode, Sebastian F. N.
Jessen, Birthe
Ammann, Sandra
Maul-Pavicic, Andrea
de Saint Basile, Genevieve
Janka, Gritta
Lehmberg, Kai
zur Stadt, Udo
Gochuico, Bernadette R.
Gahl, William A.
Klein, Christoph
Diestelhorst, Jana
Griese, Matthias
Frei-Jones, Melissa J.
Pace, David
Davies, Graham
Schwarz, Klaus
Griffiths, Gillian
Ehl, Stephan
TI DOES HERMANSKY PUDLAK SYNDROME TYPE 2 REPRESENT AN INDICATION FOR
HEMATOPOETIC STEM CELL TRANSPLANTATION?
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Bode, Sebastian F. N.; Jessen, Birthe; Ammann, Sandra; Maul-Pavicic, Andrea; Ehl, Stephan] Univ Med Ctr Freiburg, Ctr Chron Immunodeficiency, Freiburg, Germany.
[Bode, Sebastian F. N.; Jessen, Birthe; Ammann, Sandra; Maul-Pavicic, Andrea; Ehl, Stephan] Univ Freiburg, Freiburg, Germany.
[de Saint Basile, Genevieve] Univ Paris 05, INSERM, U768, Hop Necker Enfants Malad, Paris, France.
[Janka, Gritta; Lehmberg, Kai] Univ Med Ctr Hamburg Eppendorf, Dept Pediat Hematol & Oncol, Hamburg, Germany.
[zur Stadt, Udo] Univ Med Ctr Hamburg Eppendorf, Ctr Diagnost, Hamburg, Germany.
[Gochuico, Bernadette R.; Gahl, William A.] NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Klein, Christoph; Diestelhorst, Jana; Griese, Matthias] Univ Munich, Dept Pediat, Dr von Hauner Childrens Hosp, Munich, Germany.
[Frei-Jones, Melissa J.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Pace, David] Mater Dei Hosp, Dept Paediat, Msida, Malta.
[Davies, Graham] Great Ormond St Hosp Sick Children, Dept Immunol, London WC1N 3JH, England.
[Schwarz, Klaus] Univ Ulm, Inst Transfus Med, D-89069 Ulm, Germany.
[Griffiths, Gillian] Addenbrookes Hosp, Cambridge Inst Med Res, Cambridge, England.
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 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD SEP
PY 2013
VL 60
IS 9
BP E72
EP E72
PG 1
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 181XM
UT WOS:000321703900011
ER
PT J
AU Galiwango, RM
Musoke, R
Lubyayi, L
Ssekubugu, R
Kalibbala, S
Ssekweyama, V
Mirembe, V
Nakigozi, G
Reynolds, SJ
Serwadda, D
Gray, RH
Kigozi, G
AF Galiwango, Ronald M.
Musoke, Richard
Lubyayi, Lawrence
Ssekubugu, Robert
Kalibbala, Sarah
Ssekweyama, Viola
Mirembe, Viola
Nakigozi, Gertrude
Reynolds, Steven J.
Serwadda, David
Gray, Ronald H.
Kigozi, Godfrey
TI Evaluation of current rapid HIV test algorithms in Rakai, Uganda
SO JOURNAL OF VIROLOGICAL METHODS
LA English
DT Article
DE HIV; Rapids testing; Rakai-Uganda; Algorithms
ID FIELD
AB Rapid HIV tests are a crucial component of HIV diagnosis in resource limited settings. In Uganda, the Ministry of Health allows both serial and parallel HIV rapid testing using Determine, Stat-Pak and Uni-Gold. In serial testing, a non-reactive result on Determine ends testing. The performance of serial and parallel algorithms with Determine and Stat-Pak test kits was assessed. A cross-sectional diagnostic test accuracy evaluation using three rapid HIV test kits as per the recommended parallel test algorithm was followed by EIA-WB testing with estimates of the performance of serial testing algorithm. In 2520 participants tested by parallel rapid algorithms, 0.6% had weakly reactive result. Parallel testing had 99.7% sensitivity and 99.8% specificity. If Stat-Pak was used as the first screening test for a serial algorithm, the sensitivity was 99.6% and specificity was 99.7%. However, if Determine was used as the screening test, sensitivity was 97.3% and specificity was 99.9%. Serial testing with Stat-Pak as the initial screening test performed as well as parallel testing, but Determine was a less sensitive screen. Serial testing could be cost saving. (C) 2013 Elsevier B.V. All rights reserved.
C1 [Galiwango, Ronald M.; Musoke, Richard; Lubyayi, Lawrence; Ssekubugu, Robert; Kalibbala, Sarah; Ssekweyama, Viola; Mirembe, Viola; Nakigozi, Gertrude; Reynolds, Steven J.; Serwadda, David; Kigozi, Godfrey] Rakai Hlth Sci Program, Kalisizo, Uganda.
[Gray, Ronald H.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Reynolds, Steven J.] NIAID, Immunoregulat Lab, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Serwadda, David] Makerere Coll Hlth Sci, Sch Publ Hlth, Kampala, Uganda.
[Reynolds, Steven J.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA.
RP Galiwango, RM (reprint author), Rakai Hlth Sci Program, Kalisizo, Uganda.
EM rmgaliwango@rhsp.org
FU Gates Foundation [22006.03]; Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health
FX This work was supported in part by the Gates Foundation under Grant
number 22006.03 and the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health.
NR 13
TC 11
Z9 11
U1 1
U2 12
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-0934
J9 J VIROL METHODS
JI J. Virol. Methods
PD SEP
PY 2013
VL 192
IS 1-2
BP 25
EP 27
DI 10.1016/j.jviromet.2013.04.003
PG 3
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Virology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Virology
GA 174NH
UT WOS:000321162200004
PM 23583487
ER
PT J
AU Blair, KS
Otero, M
Teng, C
Jacobs, M
Odenheimer, S
Pine, DS
Blair, RJR
AF Blair, Karina S.
Otero, Marcela
Teng, Cindy
Jacobs, Madeline
Odenheimer, Stephanie
Pine, Daniel S.
Blair, R. J. R.
TI Dissociable roles of ventromedial prefrontal cortex (vmPFC) and rostral
anterior cingulate cortex (rACC) in value representation and optimistic
bias
SO NEUROIMAGE
LA English
DT Article
DE fMRI; Ventromedial prefrontal cortex; Rostral anterior cingulate cortex;
Optimistic bias
ID FUTURE LIFE EVENTS; UNREALISTIC OPTIMISM; SUBJECTIVE VALUE; HUMAN BRAIN;
CHOICE; SELF; RISK
AB Optimistic bias (OB) is seen when individuals underestimate their probability of experiencing negative life events and overestimate their probability of experiencing positive life events. A reduced OB has been linked with increased depression symptoms. However, given the relevance of this information to mood and anxiety disorders, little is currently known regarding the neurobiology of OB. In the current study, we examine the neural basis of OB in healthy individuals (n = 33) during probability estimation of future positive and negative events occurring to themselves relative to other, comparable individuals. In line with previous work, subjects showed significant OB; they considered themselves significantly more likely to experience future positive and significantly less likely to experience future negative events relative to comparable others. Positive, relative to negative events, un-modulated by subjects' probability estimates, were associated with significantly greater activity within the ventromedial prefrontal cortex (vmPFC) and posterior cingulate cortex (PCC). Moreover, responses within both regions to positive events negatively related to the healthy subjects' self reports of depression symptoms. However, there was no significant modulation of activity in either region by the subject's OB, objectified as the level to which they thought the event was more likely [positive events] or less likely [negative events] to occur to them relative to comparable others. In contrast, activity within the rostral anterior cingulate cortex (rACC) was positively modulated by OB for positive events and activity within the anterior insula and dorsomedial prefrontal cortex (dmPFC) was negatively modulated by OB for negative events. However, there was no significant relationship between responsiveness within these regions and self reports of depression symptoms. The data are discussed with reference to current models of vmPFC, rACC and anterior insula functioning. Published by Elsevier Inc.
C1 [Blair, Karina S.; Otero, Marcela; Teng, Cindy; Jacobs, Madeline; Odenheimer, Stephanie; Pine, Daniel S.; Blair, R. J. R.] NIMH, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Blair, KS (reprint author), NIMH, 15K North Dr,MSC 2670, Bethesda, MD 20892 USA.
EM peschark@mail.nih.gov
OI Teng, Cindy/0000-0002-2611-1791
FU NIH: NIMH
FX This research was supported by the Intramural Research Program of the
NIH: NIMH.
NR 25
TC 12
Z9 14
U1 5
U2 25
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD SEP
PY 2013
VL 78
BP 103
EP 110
DI 10.1016/j.neuroimage.2013.03.063
PG 8
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 165MV
UT WOS:000320488900011
PM 23567883
ER
PT J
AU Liu, JJV
Hirano, Y
Nascimento, GC
Stefanovic, B
Leopold, DA
Silva, AC
AF Liu, Junjie V.
Hirano, Yoshiyuki
Nascimento, George C.
Stefanovic, Bojana
Leopold, David A.
Silva, Afonso C.
TI fMRI in the awake marmoset: Somatosensory-evoked responses, functional
connectivity, and comparison with propofol anesthesia
SO NEUROIMAGE
LA English
DT Article
DE Awake non-human primate; Functional MRI; New world monkey;
Neuroanesthesia; Resting-state functional connectivity
ID MEDIAN NERVE-STIMULATION; MONKEYS LATERAL BELT; BOLD SIGNAL CHANGES;
AUDITORY-CORTEX; THALAMIC CONNECTIONS; CALLITHRIX-JACCHUS;
NONHUMAN-PRIMATES; MACAQUE MONKEYS; CEREBRAL-CORTEX; PERCEPTUAL
SUPPRESSION
AB Functional neuroimaging in animal models is essential for understanding the principles of neurovascular coupling and the physiological basis of fMRI signals that are widely used to study sensory and cognitive processing in the human brain. While hemodynamic responses to sensory stimuli have been characterized in humans, animal studies are able to combine very high resolution imaging with invasive measurements and pharmacological manipulation. To date, most high-resolution studies of neurovascular coupling in small animals have been carried out in anesthetized rodents. Here we report fMRI experiments in conscious, awake common marmosets (Callithrix jacchus), and compare responses to animals anesthetized with propofol. In conscious marmosets, robust BOLD fMRI responses to somatosensory stimulation of the forearm were found in contralateral and ipsilateral regions of the thalamus, primary (SI) and secondary (SII) somatosensory cortex, and the caudate nucleus. These responses were markedly stronger than those in anesthetized marmosets and showed a monotonic increase in the amplitude of the BOLD response with stimulus frequency. On the other hand, anesthesia significantly attenuated responses in thalamus, SI and SII, and abolished responses in caudate and ipsilateral SI. Moreover, anesthesia influenced several other aspects of the fMRI responses, including the shape of the hemodynamic response function and the interareal (SI-SII) spontaneous functional connectivity. Together, these findings demonstrate the value of the conscious, awake marmoset model for studying physiological responses in the somatosensory pathway, in the absence of anesthesia, so that the data can be compared most directly to fMRI in conscious humans. Published by Elsevier Inc.
C1 [Liu, Junjie V.; Hirano, Yoshiyuki; Nascimento, George C.; Stefanovic, Bojana; Silva, Afonso C.] NINDS, Cerebral Microcirculat Unit, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
[Leopold, David A.] NIMH, Sect Cognit Neurophysiol & Imaging, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
[Leopold, David A.] NEI, Neurophysiol Imaging Facil, NIMH, NINDS,NIH, Bethesda, MD 20892 USA.
RP Silva, AC (reprint author), NINDS, Cerebral Microcirculat Unit, Lab Funct & Mol Imaging, NIH, 10 Ctr Dr,Bldg 10,Room B1D106, Bethesda, MD 20892 USA.
EM liu@junjie.com; hirano@chiba-u.jp; georgegcn@gmail.com;
bojana@sri.utoronto.ca; SilvaA@ninds.nih.gov
OI Leopold, David/0000-0002-1345-6360
FU NINDS, National Institutes of Health
FX We thank Xianfeng (Lisa) Zhang, Julie Mackel, Peter Minnig and Dr. James
O'Malley for their invaluable help in animal preparation. We also thank
Dr. Brian Wandell and his colleagues at Stanford University for
providing the mrVista software on their website. This research was
supported by the Intramural Research Program of the NINDS, National
Institutes of Health.
NR 83
TC 29
Z9 29
U1 3
U2 24
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD SEP
PY 2013
VL 78
BP 186
EP 195
DI 10.1016/j.neuroimage.2013.03.038
PG 10
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 165MV
UT WOS:000320488900018
PM 23571417
ER
PT J
AU Komlosh, ME
Ozarslan, E
Lizak, MJ
Horkayne-Szakaly, I
Freidlin, RZ
Horkay, F
Basser, PJ
AF Komlosh, M. E.
Oezarslan, E.
Lizak, M. J.
Horkayne-Szakaly, I.
Freidlin, R. Z.
Horkay, F.
Basser, P. J.
TI Mapping average axon diameters in porcine spinal cord white matter and
rat corpus callosum using d-PFG MRI
SO NEUROIMAGE
LA English
DT Article
DE MRI; Average axon diameter; AAD; Pulsed-field gradient; PFG; Double wave
vector; d-PFG; dPFG; 3D
ID MICROSCOPIC DIFFUSION ANISOTROPY; COMPARTMENT SHAPE ANISOTROPY; FIELD
GRADIENT MR; WATER DIFFUSION; ELECTRON MICROSCOPY; NMR; DIFFRACTION;
TENSOR; BRAIN; SIZE
AB Knowledge of microstructural features of nerve fascicles, such as their axon diameter, is crucial for understanding normal function in the central and peripheral nervous systems as well as assessing changes due to pathologies. In this study double-pulsed field gradient (d-PFG) filtered MRI was used to map the average axon diameter (AAD) in porcine spinal cord, which was then compared to AADs measured with optical microscopy of the same specimen, as a way to further validate this new MRI method. A novel 3D d-PFG acquisition scheme was used to obtain AADs in each voxel of a coronal slice of rat brain corpus callosum. AAD measurements were also acquired using optical microscopy performed on histological sections and validated using a glass capillary array phantom. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Komlosh, M. E.; Oezarslan, E.; Horkay, F.; Basser, P. J.] NICHD, Sect Tissue Biophys & Biomimet, PPITS, NIH, Bethesda, MD 20892 USA.
[Komlosh, M. E.; Oezarslan, E.] Uniform Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA.
[Oezarslan, E.] Harvard Univ, Brigham & Womens Hosp, Dept Radiol, Sch Med, Boston, MA 02215 USA.
[Lizak, M. J.] NINDS, NIH MRI Res Facil, NIH, Bethesda, MD 20892 USA.
[Horkayne-Szakaly, I.] Dept Def, Joint Pathol Ctr, Silver Spring, MD 20910 USA.
[Freidlin, R. Z.] NIH, Ctr Informat Technol, Bethesda, MD 20892 USA.
RP Komlosh, ME (reprint author), NIH, Bldg 13 Rm 3W16,13 South Dr, Bethesda, MD 20892 USA.
EM komloshm@mail.nih.gov
RI Ozarslan, Evren/B-4858-2013
OI Ozarslan, Evren/0000-0003-0859-1311
FU CNRM; Henry Jackson Foundation; NIH [R01MH074794]; Eunice Kennedy
Shriver National Institute of Child Health and Human Development, NIH;
Center for Information Technology, NIH
FX MK and EO were supported by funds from the CNRM and Henry Jackson
Foundation. EO was supported in part by NIH R01MH074794. PJB and FH were
supported by the Intramural Research Program of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development, NIH.
RZF was supported by the Center for Information Technology, NIH. We are
grateful to Mr. R R Clevenger, Mr. T. J. Hunt Mrs. Joni Taylor, Ms. G.
J. Zywicke, Mr. A. D. Zetts, Mrs. K. Keeran, Mr. S. M. Kozlov, and Mr.
K. R. Jeffries, from LAMS, NHLBI, and Dr. M. D. Budde from the
Department of Neurosurgery, Medical College of Wisconsin for obtaining
the specimens. We would also like to thank Dr. Doug Morris from the
NMRF/NINDS for assistance with the instrumentation and Dan Benjamini for
fruitful discussions.
NR 42
TC 16
Z9 17
U1 1
U2 24
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD SEP
PY 2013
VL 78
BP 210
EP 216
DI 10.1016/j.neuroimage.2013.03.074
PG 7
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 165MV
UT WOS:000320488900021
PM 23583426
ER
PT J
AU Robinson, OJ
Overstreet, C
Allen, PS
Letkiewicz, A
Vytal, K
Pine, DS
Grillon, C
AF Robinson, Oliver J.
Overstreet, Cassie
Allen, Philip S.
Letkiewicz, Alison
Vytal, Katherine
Pine, Daniel S.
Grillon, Christian
TI The role of serotonin in the neurocircuitry of negative affective bias:
Serotonergic modulation of the dorsal medial prefrontal-amygdala
'aversive amplification' circuit
SO NEUROIMAGE
LA English
DT Article
DE Serotonin; ATD; Amygdala; dMPFC; Negative bias; Aversive amplification
ID ACUTE TRYPTOPHAN DEPLETION; ANTERIOR CINGULATE CORTEX;
POSTTRAUMATIC-STRESS-DISORDER; GENERALIZED ANXIETY DISORDER; FEAR
EXTINCTION; BEHAVIORAL-INHIBITION; HEALTHY-VOLUNTEERS; MOOD DISORDERS;
ACTIVATION; DEPRESSION
AB Serotonergic medications can mitigate the negative affective biases in disorders such as depression or anxiety, but the neural mechanism by which this occurs is largely unknown. In line with recent advances demonstrating that negative affective biases may be driven by specific medial prefrontal-amygdala circuitry, we asked whether serotonin manipulation can alter affective processing within a key dorsal medial prefrontal-amygdala circuit: the putative human homologue of the rodent prelimbic-amygdala circuit or 'aversive amplification' circuit. In a double-blind, placebo-controlled crossover pharmaco-fMRI design, subjects (N = 19) performed a forced-choice face identification task with word distractors in an fMRI scanner over two separate sessions. On one session subjects received dietary depletion of the serotonin precursor tryptophan while on the other session they received a balanced placebo control diet. Results showed that dorsal medial prefrontal responding was elevated in response to fearful relative to happy faces under depletion but not placebo. This negative bias under depletion was accompanied by a corresponding increase in positive dorsal medial prefrontal-amygdala functional connectivity. We therefore conclude that serotonin depletion engages a prefrontal-amygdala circuit during the processing of fearful relative to happy face stimuli. This same 'aversive amplification' circuit is also engaged during anxiety induced by shock anticipation. As such, serotonergic projections may inhibit engagement of the 'aversive amplification' circuit and dysfunction in this projection may contribute to the negative affective bias in mood and anxiety disorders. These findings thus provide a promising explanation for the role of serotonin and serotonergic medications in the neurocircuitry of negative affective bias. Published by Elsevier Inc.
C1 [Robinson, Oliver J.; Overstreet, Cassie; Allen, Philip S.; Letkiewicz, Alison; Vytal, Katherine; Grillon, Christian] NIMH, Sect Neurobiol Fear & Anxiety, NIH, Bethesda, MD 20892 USA.
[Pine, Daniel S.] NIMH, Sect Dev & Affect Neurosci, NIH, Bethesda, MD 20892 USA.
RP Robinson, OJ (reprint author), 15K North Dr, Bethesda, MD 20892 USA.
EM oliver.j.robinson@gmail.com
FU National Institutes of Mental Health
FX This research was supported by the Intramural Research Program of the
National Institutes of Mental Health. We are grateful to Michael
Jackson, Angie Wu, Joan Mallinger and Michael Franklin for enormous
amounts of help and support.
NR 57
TC 14
Z9 15
U1 1
U2 35
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD SEP
PY 2013
VL 78
BP 217
EP 223
DI 10.1016/j.neuroimage.2013.03.075
PG 7
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 165MV
UT WOS:000320488900022
PM 23583742
ER
PT J
AU Rosas, SR
Schouten, JT
Cope, MT
Kagan, JM
AF Rosas, Scott R.
Schouten, Jeffrey T.
Cope, Marie T.
Kagan, Jonathan M.
TI Modeling the dissemination and uptake of clinical trials results
SO RESEARCH EVALUATION
LA English
DT Article
DE dissemination; uptake; citation milestones; scientific output
ID TRANSLATIONAL RESEARCH; BIOMEDICAL-RESEARCH; TIME; IMPROVEMENT;
GUIDELINES; CITATION; METRICS; SCIENCE; HEALTH
AB A select set of highly cited publications from the National Institutes of Health (NIH) HIV/AIDS Clinical Trials Networks was used to illustrate the integration of time interval and citation data, modeling the progression, dissemination, and uptake of primary research findings. Following a process marker approach, the pace of initial utilization of this research was measured as the time from trial conceptualization, development and implementation, through results dissemination and uptake. Compared to earlier studies of clinical research, findings suggest that select HIV/AIDS trial results are disseminated and utilized relatively rapidly. Time-based modeling of publication results as they meet specific citation milestones enabled the observation of points at which study results were present in the literature summarizing the evidence in the field. Evaluating the pace of clinical research, results dissemination, and knowledge uptake in synthesized literature can help establish realistic expectations for the time course of clinical trials research and their relative impact toward influencing clinical practice.
C1 [Rosas, Scott R.; Cope, Marie T.] Concept Syst Inc, Ithaca, NY 14850 USA.
[Schouten, Jeffrey T.] Fred Hutchinson Canc Res Ctr, Off HIV AIDS Network Coordinat, Seattle, WA 98109 USA.
[Kagan, Jonathan M.] NIAID, Div Clin Res, NIH, Bethesda, MD 20892 USA.
RP Rosas, SR (reprint author), Concept Syst Inc, 136 East State St, Ithaca, NY 14850 USA.
EM srosas@conceptsystems.com
FU Intramural NIH HHS [Z99 AI999999]; NIAID NIH HHS [N01AI50022, U01
AI068614, N01 AI050022]
NR 24
TC 8
Z9 8
U1 0
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0958-2029
J9 RES EVALUAT
JI Res. Evaluat.
PD SEP
PY 2013
VL 22
IS 3
BP 179
EP 186
DI 10.1093/reseval/rvt005
PG 8
WC Information Science & Library Science
SC Information Science & Library Science
GA 173DZ
UT WOS:000321059600004
PM 24808630
ER
PT J
AU Hargreave, M
Jensen, A
Deltour, I
Brinton, LA
Andersen, KK
Kjaer, SK
AF Hargreave, Marie
Jensen, Allan
Deltour, Isabelle
Brinton, Louise A.
Andersen, Klaus K.
Kjaer, Susanne K.
TI Increased risk for cancer among offspring of women with fertility
problems
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE infertility; fertility treatment; childhood cancer
ID IN-VITRO FERTILIZATION; ASSISTED REPRODUCTIVE TECHNOLOGY; CHILDRENS
ONCOLOGY GROUP; CHILDHOOD LEUKEMIA; YOUNG-ADULTS; BORN; INFERTILITY;
PREGNANCY; DIETHYLSTILBESTROL; RETINOBLASTOMA
AB Some studies have indicated that children born after fertility treatment have a potential risk for cancer, but the results are inconsistent. Furthermore, any negative effects of fertility treatment might be due to the underlying infertility rather than to the procedure itself. In the largest cohort study to date with information on fertility, we examined whether the offspring of women with fertility problems had a higher risk for cancer than offspring of women without fertility problems. The study cohort consisted of 2,830,054 offspring born in Denmark between 1964 and 2006. Of these, 125,844 were offspring of women evaluated for infertility. Cox regression models were used to estimate the possible effect of being the offspring of a woman evaluated for infertility on the risk for cancer. Analyses were performed separately for cancer during childhood (0-19 years) and cancer in young adulthood (>20 years). We found that offspring born to women with fertility problems had higher overall risks for cancer in childhood (hazard ratio (HR), 1.18; 95% confidence interval (CI), 1.05-1.32) and in young adulthood (HR, 1.22; 95% CI, 1.04-1.43) than offspring of women without fertility problems. Offspring of women with fertility problems had significantly increased risks for leukemia in childhood (HR, 1.30; 95% CI, 1.06-1.60) and for cancer of the endocrine glands in young adulthood (HR, 2.67; 95% CI, 1.35-5.29). These findings suggest that offspring born to mothers with fertility problems are at increased risk for cancer in both childhood and young adulthood. If real, our findings of an approximate to 18% overall increase in risk for cancer in childhood and an approximate to 22% overall increase in risk for cancer in young adulthood would mean about four additional cases of childhood cancer and about nine additional cases of cancer in young adults per 100,000 exposed offspring.
C1 [Hargreave, Marie; Jensen, Allan; Kjaer, Susanne K.] Danish Canc Soc, Res Ctr, Unit Virus Lifestyle & Genes, DK-2100 Copenhagen, Denmark.
[Deltour, Isabelle] Int Agcy Res Canc, Sect Environm & Radiat, F-69372 Lyon, France.
[Brinton, Louise A.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Andersen, Klaus K.; Kjaer, Susanne K.] Danish Canc Soc, Res Ctr, DK-2100 Copenhagen, Denmark.
[Kjaer, Susanne K.] Univ Copenhagen, Rigshosp, Dept Obstet & Gynecol, DK-1168 Copenhagen, Denmark.
RP Kjaer, SK (reprint author), Danish Canc Soc, Res Ctr, DK-2100 Copenhagen, Denmark.
EM susanne@cancer.dk
RI Brinton, Louise/G-7486-2015;
OI Brinton, Louise/0000-0003-3853-8562; Kjaer, Susanne/0000-0002-8347-1398
FU Savvaerksejer Jeppe Juhl og Hustru Ovita Juhls Foundation
FX Grant sponsor: Savvaerksejer Jeppe Juhl og Hustru Ovita Juhls Foundation
NR 33
TC 7
Z9 7
U1 0
U2 15
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD SEP 1
PY 2013
VL 133
IS 5
BP 1180
EP 1186
DI 10.1002/ijc.28110
PG 7
WC Oncology
SC Oncology
GA 166MT
UT WOS:000320559600018
PM 23404395
ER
PT J
AU Davis, MA
Gray, RH
Grabowski, MK
Serwadda, D
Kigozi, G
Gravitt, PE
Nalugoda, F
Watya, S
Wawer, MJ
Quinn, TC
Tobian, AAR
AF Davis, Mitzie-Ann
Gray, Ronald H.
Grabowski, Mary K.
Serwadda, David
Kigozi, Godfrey
Gravitt, Patti E.
Nalugoda, Fred
Watya, Stephen
Wawer, Maria J.
Quinn, Thomas C.
Tobian, Aaron A. R.
TI Male circumcision decreases high-risk human papillomavirus viral load in
female partners: A randomized trial in Rakai, Uganda
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE human papillomavirus; male circumcision; Uganda; cervical cancer;
sexually transmitted infections; viral shedding; viral load; linear
array band intensity; HIV
ID HIV-NEGATIVE MEN; CERVICAL-CANCER; PREVALENCE; INFECTION; PREVENTION;
CLEARANCE; CYTOLOGY; AFRICA; WOMEN
AB Male circumcision (MC) reduces high-risk human papillomavirus (HR-HPV) infection in female partners. We evaluated the intensity of HR-HPV viral DNA load in HIV-negative, HR-HPV-positive female partners of circumcised and uncircumcised men. HIV-negative men and their female partners were enrolled in randomized trials of MC in Rakai, Uganda. Vaginal swabs were tested for HR-HPV genotypes by Roche HPV Linear Array which provides a semi-quantitative measure of HPV DNA by the intensity of genotype-specific bands (graded:1-4). We assessed the effects of MC on female HR-HPV DNA load by comparing high intensity linear array bands (3-4) to low intensity bands (1-2) using an intention-to-treat analysis. Prevalence risk ratios (PRR) of high intensity bands in partners of intervention versus control arm men were estimated using log-binomial regression with robust variance. The trial included 335 women with male partners in the intervention arm and 340 in the control arm. At enrollment, the frequency of HR-HPV high intensity linear array bands was similar in both study arms. At 24 months follow-up, the prevalence of high intensity bands among women with detectable HR-HPV was significantly lower in partners of intervention arm (42.7%) than control arm men (55.1%, PRR=0.78, 95%CI 0.65-0.94, p=0.02), primarily among incident HR-HPV infections (PRR=0.66, 95% CI 0.50-0.87, p=0.003), but not persistent infections (PRR=1.02, 95% CI 0.83-1.24). Genotypes with high HR-HPV band intensity were more likely to persist (adjHR=1.27 95% CI 1.07-1.50), irrespective of male partner circumcision status. MC reduces HR-HPV DNA load in newly infected female partners.
C1 [Davis, Mitzie-Ann] UCSD, Moores Canc Ctr, Dept Gynecol Oncol, La Jolla, CA USA.
[Davis, Mitzie-Ann; Gray, Ronald H.; Grabowski, Mary K.; Gravitt, Patti E.; Wawer, Maria J.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21287 USA.
[Gray, Ronald H.; Serwadda, David; Kigozi, Godfrey; Nalugoda, Fred; Wawer, Maria J.; Quinn, Thomas C.; Tobian, Aaron A. R.] Rakai Hlth Sci Program, Entebbe, Uganda.
[Serwadda, David] Makerere Univ, Sch Publ Hlth, Kampala, Uganda.
[Gravitt, Patti E.] Perdana Univ, Grad Sch Med, Serdang, Malaysia.
[Watya, Stephen] Makerere Univ, Dept Urol, Kampala, Uganda.
[Quinn, Thomas C.] Johns Hopkins Univ, Dept Med, Sch Med, Baltimore, MD 21287 USA.
[Quinn, Thomas C.] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Tobian, Aaron A. R.] Johns Hopkins Univ, Dept Pathol, Sch Med, Baltimore, MD 21287 USA.
RP Tobian, AAR (reprint author), Johns Hopkins Univ, Dept Pathol, Carnegie 437,600 N Wolfe St, Baltimore, MD 21287 USA.
EM atobian1@jhmi.edu
FU National Institutes of Health [UO1AI51171]; Bill and Melinda Gates
Foundation [22006.02]; Fogarty International Center [5D43TW001508,
2D43TW000010-19-AITRP]; National Institute of Allergy and Infectious
Diseases (NIAID); NIH [U01-AI-068613, 3U01-AI075115-03S1,
1K23AI093152-01A1]; NIAID; Doris Duke Charitable Foundation [22006.02]
FX Grant sponsor: National Institutes of Health; Grant number: #UO1AI51171;
Grant sponsor: Bill and Melinda Gates Foundation; Grant number:
#22006.02; Grant sponsor: Fogarty International Center; Grant numbers:
5D43TW001508 and #2D43TW000010-19-AITRP; Grant sponsor: National
Institute of Allergy and Infectious Diseases (NIAID); Grant sponsor:
NIH; Grant numbers: U01-AI-068613 and 3U01-AI075115-03S1; Grant sponsor:
NIAID Intramural Program; Grant sponsor: NIH; Grant number:
1K23AI093152-01A1; Grant sponsor: Doris Duke Charitable Foundation
Clinician Scientist Development Award; Grant number: #22006.02
NR 25
TC 12
Z9 13
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD SEP 1
PY 2013
VL 133
IS 5
BP 1247
EP 1252
DI 10.1002/ijc.28100
PG 6
WC Oncology
SC Oncology
GA 166MT
UT WOS:000320559600025
PM 23400966
ER
PT J
AU Yewdell, JW
AF Yewdell, Jonathan W.
TI Amsterdamming DRiPs
SO MOLECULAR IMMUNOLOGY
LA English
DT Review
DE Antigen Processing; DRiP; MHC class I; Proteolysis; T cell; Virus
ID MESSENGER-RNA; PEPTIDES; TRANSLATION
AB The field of antigen processing and presentation has taken tremendous strides since the first international workshop in 1995. While much has been learned, much remains to be discovered. Here I discuss the most recent findings regarding the nature of substrates for the MHC class I antigen processing pathways which provide glimpses of the mist shrouded features remaining to be discovered. Published by Elsevier Ltd.
C1 NIAID, Viral Dis Lab, Bethesda, MD 20892 USA.
RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, Bethesda, MD 20892 USA.
EM jyewdell@nih.gov
FU Intramural NIH HHS [Z01 AI000542-20, Z01 AI000653-16]
NR 7
TC 0
Z9 0
U1 0
U2 19
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0161-5890
J9 MOL IMMUNOL
JI Mol. Immunol.
PD SEP
PY 2013
VL 55
IS 2
SI SI
BP 110
EP 112
DI 10.1016/j.molimm.2012.10.023
PG 3
WC Biochemistry & Molecular Biology; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA 129XI
UT WOS:000317876900003
PM 23266429
ER
PT J
AU Mage, MG
Dolan, MA
Wang, R
Boyd, LF
Revilleza, MJ
Robinson, H
Natarajan, K
Myers, NB
Hansen, TH
Margulies, DH
AF Mage, Michael G.
Dolan, Michael A.
Wang, Rui
Boyd, Lisa F.
Revilleza, Maria Jamela
Robinson, Howard
Natarajan, Kannan
Myers, Nancy B.
Hansen, Ted H.
Margulies, David H.
TI A structural and molecular dynamics approach to understanding the
peptide-receptive transition state of MHC-I molecules
SO MOLECULAR IMMUNOLOGY
LA English
DT Review
DE Antigen presentation; MHC-I structure and function; Peptide loading;
X-ray crystallography; Molecular dynamics
AB The mature conformation of major histocompatibility complex class I (MHC-I) proteins depends on the presence of bound peptides, permitting recognition at the cell surface by CD8(+) T lymphocytes. Newly synthesized MHC-I molecules in the endoplasmic reticulum are maintained in a peptide-receptive (PR) transition state by several chaperones until they are released concomitant with the loading of peptides. By determining the crystallographic structure of a region of an MHC-I molecule that is recognized by a unique monoclonal antibody and comparing this with docking and molecular dynamics simulations with the whole molecule, we demonstrate the movement of a hinged unit supporting the part of the binding groove that interacts with the amino terminal residues of the bound peptide. This unit contains a conserved 310 helix that flips from an exposed "open" position in the PR form to a "closed" position in the peptide-loaded (PL) mature molecule. These analyses indicate how this segment of the MHC-I molecule moves to help establish the A and B pockets critical for tight peptide binding and the stable structure required for antigen presentation and T cell recognition at the cell surface. Published by Elsevier Ltd.
C1 [Mage, Michael G.; Wang, Rui; Boyd, Lisa F.; Revilleza, Maria Jamela; Natarajan, Kannan; Margulies, David H.] NIAID, Mol Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Dolan, Michael A.] NIAID, Computat Biol Sect, Bioinformat & Computat Biosci Branch, NIH, Bethesda, MD 20892 USA.
[Robinson, Howard] Brookhaven Natl Lab, Natl Synchrotron Light Source, Upton, NY 11973 USA.
[Myers, Nancy B.; Hansen, Ted H.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
RP Mage, MG (reprint author), NIAID, NIH, 10 Ctr Dr,Bldg 10,Room 11N311, Bethesda, MD 20892 USA.
EM mmage@mail.nih.gov; dhm@nih.gov
RI Margulies, David/H-7089-2013;
OI Margulies, David/0000-0001-8530-7375
FU National Institute of Allergy and Infectious Diseases; National
Institutes of Health [AI019687]
FX This research was supported by the intramural research program of the
National Institute of Allergy and Infectious Diseases as well as by
National Institutes of Health Grant AI019687 (to T.H.H.).
NR 6
TC 5
Z9 5
U1 1
U2 107
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0161-5890
J9 MOL IMMUNOL
JI Mol. Immunol.
PD SEP
PY 2013
VL 55
IS 2
SI SI
BP 123
EP 125
DI 10.1016/j.molimm.2012.10.021
PG 3
WC Biochemistry & Molecular Biology; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA 129XI
UT WOS:000317876900007
PM 23200143
ER
PT J
AU Suway, JG
White, LK
Vanderwert, RE
Bar-Haim, Y
Pine, DS
Fox, NA
AF Suway, J. G.
White, L. K.
Vanderwert, R. E.
Bar-Haim, Y.
Pine, D. S.
Fox, N. A.
TI Modification of threat-processing in non-anxious individuals: A
preliminary, behavioral and ERP study
SO JOURNAL OF BEHAVIOR THERAPY AND EXPERIMENTAL PSYCHIATRY
LA English
DT Article
DE Attention bias; Anxiety; ERP; Attention bias modification
ID EVENT-RELATED POTENTIALS; ATTENTIONAL BIAS; SELECTIVE ATTENTION; ANXIETY
DISORDER; PLASTICITY; REACTIVITY
AB Background and objectives: Previous research suggests that attention bias toward threat contributes to the development and maintenance of anxiety. The current study extends this work by mapping the neural correlates of experimentally-induced changes in attention bias. The study examines both behavioral and psychophysiological changes associated with experimentally-induced changes in threat bias.
Methods: Thirty-four non-anxious female adults were randomly assigned to one of two conditions: training attention toward threat or placebo control. Attention bias was assessed and trained via a modified dot-probe task. Participants completed pre- and post-training assessments of attention bias and stress reactivity. As well, EEG was collected during pre- and post-test assessment of attention bias using the dot-probe task.
Results: Training induced significant changes in attention bias, though findings were complicated by group differences in baseline threat-bias scores. Compared to controls, those in the training group showed greater depression vulnerability to a post-training stressor and increased P2 amplitude, an ERP component associated with attention toward threat, during the dot-probe task.
Limitations: Although participants were randomly assigned to groups, there were still group differences in pre-training bias scores. Also, while the use of a stress task before the initial assessment of attention bias was used to control for initial differences in stress vulnerability, this may have altered pre-bias scores since participants completed this task immediately after being stressed.
Conclusions: These findings demonstrate training-induced changes in behavior and neural response patterns relevant to work on attention bias modification. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Suway, J. G.; White, L. K.; Fox, N. A.] Univ Maryland, Dept Human Dev & Quantitat Methodol, College Pk, MD 20742 USA.
[Vanderwert, R. E.] Childrens Hosp Boston, Div Dev Med, Labs Cognit Neurosci, Boston, MA USA.
[Bar-Haim, Y.] Tel Aviv Univ, Sch Psychol Sci, Tel Aviv, Israel.
[Bar-Haim, Y.] Tel Aviv Univ, Sch Neurosci, Tel Aviv, Israel.
[Pine, D. S.] NIMH, Sect Dev & Affect Neurosci, Mood & Anxiety Program, Bethesda, MD USA.
RP Suway, JG (reprint author), Univ Maryland, 3304 Benjamin Bldg, College Pk, MD 20742 USA.
EM Jngold@umd.edu
OI Vanderwert, Ross/0000-0002-2280-8401
FU NICHD NIH HHS [R37 HD017899, R37HD17899]; NIMH NIH HHS [1F31MH085424,
F31 MH085424, P50 MH078105, P50 MH078105-01A2]
NR 29
TC 5
Z9 6
U1 1
U2 69
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0005-7916
J9 J BEHAV THER EXP PSY
JI J. Behav. Ther. Exp. Psychiatry
PD SEP
PY 2013
VL 44
IS 3
BP 285
EP 292
DI 10.1016/j.jbtep.2012.11.006
PG 8
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA 120KE
UT WOS:000317168400002
PM 23391516
ER
PT J
AU Yadav, H
Lee, JH
Lloyd, J
Walter, P
Rane, SG
AF Yadav, Hariom
Lee, Ji-Hyeon
Lloyd, John
Walter, Peter
Rane, Sushil G.
TI Beneficial Metabolic Effects of a Probiotic via Butyrate-induced GLP-1
Hormone Secretion
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID GUT-MICROBIOTA INTERACTIONS; INSULIN-RESISTANCE; PLASMA-CONCENTRATIONS;
ENERGY-EXPENDITURE; FOOD-INTAKE; OBESITY; INFLAMMATION; HEALTH; FLORA;
MICE
AB Obesity and diabetes are associated with excess caloric intake and reduced energy expenditure resulting in a negative energy balance. The incidence of diabetes has reached epidemic proportions, and childhood diabetes and obesity are increasing alarmingly. Therefore, it is important to develop safe, easily deliverable, and economically viable treatment alternatives for these diseases. Here, we provide data supporting the candidacy of probiotics as such a therapeutic modality against obesity and diabetes. Probiotics are live bacteria that colonize the gastrointestinal tract and impart beneficial effects for health. However, their widespread prescription as medical therapies is limited primarily because of the paucity of our understanding of their mechanism of action. Here, we demonstrate that the administration of a probiotic, VSL#3, prevented and treated obesity and diabetes in several mouse models. VSL#3 suppressed body weight gain and insulin resistance via modulation of the gut flora composition. VSL#3 promoted the release of the hormone GLP-1, resulting in reduced food intake and improved glucose tolerance. The VSL#3-induced changes were associated with an increase in the levels of a short chain fatty acid (SCFA), butyrate. Using a cell culture system, we demonstrate that butyrate stimulated the release of GLP-1 from intestinal L-cells, thereby providing a plausible mechanism for VSL#3 action. These findings suggest that probiotics such as VSL#3 can modulate the gut microbiota-SCFA-hormone axis. Moreover, our results indicate that probiotics are of potential therapeutic utility to counter obesity and diabetes.
C1 [Yadav, Hariom; Lee, Ji-Hyeon; Rane, Sushil G.] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA.
[Lloyd, John] NIDDK, Biol Chem Lab, NIH, Bethesda, MD 20892 USA.
[Walter, Peter] NIDDK, Clin Mass Spectrometry Core, NIH, Bethesda, MD 20892 USA.
RP Rane, SG (reprint author), NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA.
EM ranes@mail.nih.gov
OI Yadav, Hariom/0000-0003-4504-1597
FU National Institutes of Health from the Intramural Program of NIDDK
FX This work was supported, in whole or in part, by the National Institutes
of Health from the Intramural Program of NIDDK.
NR 50
TC 89
Z9 94
U1 9
U2 43
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 AUG 30
PY 2013
VL 288
IS 35
BP 25088
EP 25097
DI 10.1074/jbc.M113.452516
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 302QC
UT WOS:000330619000009
PM 23836895
ER
PT J
AU Ying, TL
Chen, WZ
Feng, Y
Wang, YP
Gong, R
Dimitrov, DS
AF Ying, Tianlei
Chen, Weizao
Feng, Yang
Wang, Yanping
Gong, Rui
Dimitrov, Dimiter S.
TI Engineered Soluble Monomeric IgG1 CH3 Domain GENERATION, MECHANISMS OF
FUNCTION, AND IMPLICATIONS FOR DESIGN OF BIOLOGICAL THERAPEUTICS
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID NEONATAL-FC-RECEPTOR; ANTIBODY DOMAIN; INCREASED-STABILITY;
CRYSTAL-STRUCTURE; BINDING-SITE; GAMMA-RIII; HALF-LIFE; GLYCOPROTEIN;
FRAGMENTS; PROTEINS
AB Most of the therapeutic antibodies approved for clinical use are full-size IgG1 molecules. The interaction of the IgG1 Fc with the neonatal Fc receptor (FcRn) plays a critical role in maintaining their long half-life. We have hypothesized that isolated Fc domains could be engineered to functionally mimic full-size IgG1 (nanoantibodies) but with decreased (10-fold) size. Here, we report for the first time the successful generation of a soluble, monomeric CH3 domain (mCH3). In contrast to the wild-type dimeric CH3, the mCH3 exhibited pH-dependent binding to FcRn similar to that of Fc. The binding free energy of mCH3 to FcRn was higher than that of isolated CH2 but lower than that of Fc. Therefore, CH3 may contribute a larger portion of the free energy of binding to FcRn than CH2. A fusion protein of mCH3 with an engineered antibody domain (m36.4) also bound to FcRn in a pH-dependent fashion and exhibited significantly higher neutralizing activity against HIV-1 than m36.4-Fc fusion proteins. The m36.4-mCH3 fusion protein was monomeric, stable, soluble, and expressed at a high level in Escherichia coli. We also found that engineering an additional disulfide bond in mCH3 remarkably increased its thermal stability, whereas the FcRn binding was not affected. These data suggest that mCH3 could not only help in the exploration of the dual mechanisms of the CH3 contribution to Fc functions (dimerization and FcRn interactions) but could also be used for the development of candidate therapeutics with optimized half-life, enhanced tissue penetration, access to sterically restricted binding sites, and increased therapeutic efficacy.
C1 [Ying, Tianlei; Chen, Weizao; Feng, Yang; Wang, Yanping; Gong, Rui; Dimitrov, Dimiter S.] NCI, Prot Interact Grp, Canc & Inflammat Program, Ctr Canc Res,NIH, Frederick, MD 21702 USA.
[Wang, Yanping] SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Ying, TL (reprint author), NCI, Prot Interact Grp, NIH, Bldg 469,Rm 150B, Frederick, MD 21702 USA.
EM yingt@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health, NCI,
Center for Cancer Research; National Institutes of Health, NCI
[N01-CO-12400]
FX This work was supported, in whole or in part, by the Intramural Research
Program of the National Institutes of Health, NCI, Center for Cancer
Research and by federal funds from the National Institutes of Health,
NCI, under Contract N01-CO-12400.
NR 37
TC 22
Z9 22
U1 1
U2 6
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 AUG 30
PY 2013
VL 288
IS 35
BP 25154
EP 25164
DI 10.1074/jbc.M113.484154
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 302QC
UT WOS:000330619000015
PM 23867459
ER
PT J
AU Heymann, JB
Bartho, JD
Rybakova, D
Venugopal, HP
Winkler, DC
Sen, A
Hurst, MRH
Mitra, AK
AF Heymann, J. Bernard
Bartho, Joseph D.
Rybakova, Daria
Venugopal, Hari P.
Winkler, Dennis C.
Sen, Anindito
Hurst, Mark R. H.
Mitra, Alok K.
TI Three-dimensional Structure of the Toxin-delivery Particle Antifeeding
Prophage of Serratia entomophila
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID COMMON EVOLUTIONARY ORIGIN; PSEUDOMONAS-AERUGINOSA; TAIL LENGTH; GRASS
GRUB; SECRETION APPARATUS; AMBER DISEASE; BACTERIOPHAGE-T4; PROTEIN;
SHEATH; PHAGE
AB The Serratia entomophila antifeeding prophage (Afp) is a bullet-shaped toxin-delivery apparatus similar to the R-pyocins of Pseudomonas aeruginosa. Morphologically it resembles the sheathed tail of bacteriophages such as T4, including a baseplate at one end. It also shares features with the type VI secretion systems. Cryo-electron micrographs of tilted Afp specimens (up to 60 degrees) were analyzed to determine the correct cyclic symmetry to overcome the limitation imposed by exclusively side views in nominally untilted specimens. An asymmetric reconstruction shows clear 6-fold cyclic symmetry contrary to a previous conclusion of 4-fold symmetry based on analysis of only the preferred side views (Sen, A., Rybakova, D., Hurst, M. R., and Mitra, A. K. (2010) J. Bacteriol. 192, 4522-4525). Electron tomography of negatively stained Afp revealed right-handed helical striations in many of the particles, establishing the correct hand. Higher quality micrographs of untilted specimens were processed to produce a reconstruction at 2.0-nm resolution with imposed 6-fold symmetry. The helical parameters of the sheath were determined to be 8.14 nm for the subunit rise along and 40.5 degrees for the rotation angle around the helix. The sheath is similar to that of the T4 phage tail but with a different arrangement of the subdomain of the polymerizing sheath protein( s). The central tube is similar to the diameter and axial width of the Hcp1 hexamer of P. aeruginosa type VI secretion system. The tube extends through the baseplate into a needle resembling the "puncture device" of the T4 tail. The tube contains density that may be the toxin and/or a length-determining protein.
C1 [Heymann, J. Bernard; Winkler, Dennis C.] NIAMS, NIH, Bethesda, MD 20892 USA.
[Bartho, Joseph D.; Venugopal, Hari P.; Sen, Anindito; Mitra, Alok K.] Univ Auckland, Sch Biol Sci, Auckland 1142, New Zealand.
[Rybakova, Daria; Hurst, Mark R. H.] Agresearch, Innovat Farm Syst, Christchurch 8140, New Zealand.
RP Mitra, AK (reprint author), Univ Auckland, Sch Biol Sci, Thomas Bldg,3A Symonds St, Auckland 1142, New Zealand.
EM a.mitra@auckland.ac.nz
OI Bartho, Joseph Dale/0000-0003-3853-2347; Heymann,
Bernard/0000-0002-8872-5326; Hurst, Mark/0000-0001-5826-5253
FU Faculty Research Development Fund from the University of Auckland;
Foundation of Research, Science and Technology, New Zealand [C10X0804];
Intramural Research Program of NIAMS, National Institutes of Health
FX This work was supported by a Faculty Research Development Fund from the
University of Auckland (to A. K. M.), by Foundation of Research, Science
and Technology, New Zealand Grant C10X0804 (to M. R. H. H.), and by the
Intramural Research Program of NIAMS, National Institutes of Health (to
J. B. H. and D. C. W.).
NR 37
TC 15
Z9 15
U1 0
U2 9
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 30
PY 2013
VL 288
IS 35
BP 25276
EP 25284
DI 10.1074/jbc.M113.456145
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 302QC
UT WOS:000330619000026
PM 23857636
ER
PT J
AU Huang, CH
Hsiao, HT
Chu, YR
Ye, YH
Chen, X
AF Huang, Chih-Hsiang
Hsiao, Hui-Ting
Chu, Yue-Ru
Ye, Yihong
Chen, Xin
TI Derlin2 Protein Facilitates HRD1-mediated Retro-translocation of Sonic
Hedgehog at the Endoplasmic Reticulum
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID UBIQUITIN LIGASE COMPLEX; MISFOLDED PROTEINS; MUTANT
ALPHA-1-ANTITRYPSIN; QUALITY-CONTROL; ERAD COMPLEX; DEGRADATION;
DISLOCATION; MEMBRANE; RETROTRANSLOCATION; RECOGNITION
AB Endoplasmic reticulum-associated degradation (ERAD) is an important system that eliminates misfolded proteins from the ER. Three derlins have been implicated in this process, but their precise function remains unknown. In this study, we report that although both derlin1 and derlin2 are capable of binding the ERAD-specific ubiquitin ligase HRD1, they associate with the HRD1-containing complex with different affinities. Accordingly, these derlins have nonredundant functions in ERAD with derlin2 being an essential functional partner for HRD1-mediated ERAD of SHH and NHK. We show that derlin2, but not derlin1 or derlin3, is required for ERAD of both glycosylated and nonglycosylated SHH, as well as NHK. Derlin2 appears to act at a post-targeting step for HRD1-dependent retro-translocation. Without derlin2, the assembly of HRD1 into a functional retro-translocation homo-oligomer proceeds normally, and substrate targeting to the HRD1 complex also occurs. However, the ERAD substrate SHH-C is largely trapped inside the ER lumen. These observations raise the possibility that derlin2 may regulate the movement of substrates through the HRD1-containing retro-translocon. Our study is the first to report that derlin2 functions with HRD1 in ERAD of certain substrates independent of their glycosylation status. The mammalian ERAD system may require multiple derlins that each functions with a distinct E3 partner to eliminate a specific subset of substrates. This is different from the model in Saccharomyces cerevisiae, in which Hrd1p alone is sufficient for retro-translocation.
C1 [Huang, Chih-Hsiang; Hsiao, Hui-Ting; Chu, Yue-Ru; Chen, Xin] Natl Hlth Res Inst, Inst Biotechnol & Pharmaceut Res, Miaoli 35053, Taiwan.
[Ye, Yihong] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Chen, Xin] China Med Univ, Grad Inst Basic Med Sci, Taichung 40402, Taiwan.
RP Chen, X (reprint author), Natl Hlth Res Inst, Inst Biotechnol & Pharmaceut Res, Zhu Nan Town 35053, Miaoli County, Taiwan.
EM xchen@nhri.org.tw
FU NRPGM (National Research Program for Genomic Medicine); National Science
Council, Taiwan; National Health Research Institutes, Taiwan, Republic
of China
FX This work was supported by NRPGM (National Research Program for Genomic
Medicine), National Science Council, Taiwan and National Health Research
Institutes, Taiwan, Republic of China.
NR 33
TC 13
Z9 13
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 AUG 30
PY 2013
VL 288
IS 35
BP 25330
EP 25339
DI 10.1074/jbc.M113.455212
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 302QC
UT WOS:000330619000031
PM 23867461
ER
PT J
AU Xie, YL
Zimmerman, DL
AF Xie, Yunlong
Zimmerman, Dale L.
TI Antedependence models for nonstationary categorical longitudinal data
with ignorable missingness: likelihood-based inference
SO STATISTICS IN MEDICINE
LA English
DT Article
DE likelihood ratio test; Markov models; missing data; transition models
ID MARKOV-CHAINS; TIME-SERIES; REGRESSION
AB Time index-ordered random variables are said to be antedependent (AD) of order (p(1),p(2),...,p(n)) if the kth variable, conditioned on the p(k) immediately preceding variables, is independent of all further preceding variables. Inferential methods associated with AD models are well developed for continuous (primarily normal) longitudinal data, but not for categorical longitudinal data. In this article, we develop likelihood-based inferential procedures for unstructured AD models for categorical longitudinal data. Specifically, we derive maximum likelihood estimators (MLEs) of model parameters; penalized likelihood criteria and likelihood ratio tests for determining the order of antedependence; and likelihood ratio tests for homogeneity across groups, time invariance of transition probabilities, and strict stationarity. We give closed-form expressions for MLEs and test statistics, which allow for the possibility of empty cells and monotone missing data, for all cases save strict stationarity. For data with an arbitrary missingness pattern, we derive an efficient restricted expectation-maximization algorithm for obtaining MLEs. We evaluate the performance of the tests by simulation. We apply the methods to longitudinal studies of toenail infection severity (measured on a binary scale) and Alzheimer's disease severity (measured on an ordinal scale). The analysis of the toenail infection severity data reveals interesting nonstationary behavior of the transition probabilities and indicates that an unstructured first-order AD model is superior to stationary and other structured first-order AD models that have previously been fit to these data. The analysis of the Alzheimer's severity data indicates that the antedependence is second order with time-invariant transition probabilities, suggesting the use of a second-order autoregressive cumulative logit model. Copyright (c) 2013 John Wiley & Sons, Ltd.
C1 [Xie, Yunlong] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA.
[Zimmerman, Dale L.] Univ Iowa, Dept Stat & Actuarial Sci, Iowa City, IA 52242 USA.
RP Xie, YL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA.
EM yunlong.xie@nih.gov
FU National Alzheimer's Coordinating Center (NACC) [U01 AG016976]; National
Institutes of health, Eunice Kennedy Shriver National Institute of Child
Health and Human Development
FX The data were from the National Alzheimer's Coordinating Center (NACC
grant number, U01 AG016976). 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. We thank the Center for Information Technology, the
National Institutes of Health, for providing access to the
high-performance computational capabilities of the Biowulf cluster.
NR 19
TC 2
Z9 2
U1 0
U2 2
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 AUG 30
PY 2013
VL 32
IS 19
BP 3274
EP 3289
DI 10.1002/sim.5763
PG 16
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 279JX
UT WOS:000328957400004
PM 23436682
ER
PT J
AU Kubler-Kielb, J
Vinogradov, E
AF Kubler-Kielb, Joanna
Vinogradov, Evgeny
TI Reinvestigation of the structure of Brucella O-antigens
SO CARBOHYDRATE RESEARCH
LA English
DT Article
DE Brucella; LPS; Structure; NMR; MS
ID LIPOPOLYSACCHARIDE; IDENTIFICATION; ELUCIDATION; CHAIN; CORE; NMR
AB O-Specific polysaccharides of Brucella contain two antigenic determinants, called A and M. Most of the strains express epitope A with a small amount of epitope M, whereas Brucella melitensis strain 16 M expresses longer polymer consisting mostly of M-type epitopes. Proposed explanation was that epitope A is defined by 1-2-linked homopolymer of N-formylperosamine (Rha4NFo), while epitope M is a pentasaccharide with four 2-and one 3-substituted Rha4NFo. We reinvestigated both types of structures by 2D NMR and showed that M-epitope is a tetrasaccharide, missing one of the 2-linked Rha4NFo as compared to the previously proposed structure. Polysaccharide from B. melitensis 16 M contains a fragment of 1-2-linked polymer, capped with M-type polymer. Other strains contain one or two M-type units at the non-reducing end of the 1-2-linked O-chain. Crown Copyright (C) 2013 Published by Elsevier Ltd. All rights reserved.
C1 [Kubler-Kielb, Joanna] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Vinogradov, Evgeny] Natl Res Council Canada, Ottawa, ON K1A 0R6, Canada.
RP Vinogradov, E (reprint author), Natl Res Council Canada, Ottawa, ON K1A 0R6, Canada.
EM evguenii.vinogradov@nrc.ca
OI Vinogradov, Evgeny/0000-0002-5364-1376
FU intramural program of NICHD, National Institutes of Health, Bethesda, MD
FX Authors are greatly indebted to Dr. M. B. Perry (NRC Canada) for
Brucella LPS samples. We thank J. Stupak and K. Chan ( NRC Canada) for
recording mass spectra. This work was partially supported by the
intramural program of NICHD, National Institutes of Health, Bethesda,
MD.
NR 11
TC 8
Z9 9
U1 2
U2 6
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0008-6215
J9 CARBOHYD RES
JI Carbohydr. Res.
PD AUG 30
PY 2013
VL 378
BP 144
EP 147
DI 10.1016/j.carres.2013.03.021
PG 4
WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic
SC Biochemistry & Molecular Biology; Chemistry
GA 216QV
UT WOS:000324299900020
PM 23664729
ER
PT J
AU Schotte, F
Cho, HS
Soman, J
Wulff, M
Olson, JS
Anfinrud, PA
AF Schotte, Friedrich
Cho, Hyun Sun
Soman, Jayashree
Wulff, Michael
Olson, John S.
Anfinrud, Philip A.
TI Real-time tracking of CO migration and binding in the alpha and beta
subunits of human hemoglobin via 150-ps time-resolved Laue
crystallography
SO CHEMICAL PHYSICS
LA English
DT Article
DE Hemoglobin; Geminate rebinding; Ligand migration; Time-resolved Laue
crystallography
ID X-RAY CRYSTALLOGRAPHY; MID-IR SPECTROSCOPY; LIGAND MIGRATION; GEMINATE
RECOMBINATION; CONFORMATIONAL-CHANGES; MOLECULAR-DYNAMICS;
CARBON-MONOXIDE; HEME-PROTEINS; MYOGLOBIN; NANOSECOND
AB We have developed the method of picosecond Laue crystallography and used this capability to probe ligand dynamics in tetrameric R-state hemoglobin (Hb). Time-resolved, 2 angstrom-resolution electron density maps of photolyzed HbCO reveal the time-dependent population of CO in the binding (A) and primary docking (B) sites of both alpha and beta subunits from 100 ps to 10 mu s. The proximity of the B site in the beta subunit is about 0.25 angstrom closer to its A binding site, and its k(BA) rebinding rate (similar to 300 mu s (1)) is six times faster, suggesting distal control of the rebinding dynamics. Geminate rebinding in the beta subunit exhibits both prompt and delayed geminate phases. We developed a microscopic model to quantitatively explain the observed kinetics, with three states for the alpha subunit and four states for the beta subunit. This model provides a consistent framework for interpreting rebinding kinetics reported in prior studies of both HbCO and HbO(2). Published by Elsevier B.V.
C1 [Schotte, Friedrich; Cho, Hyun Sun; Anfinrud, Philip A.] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Soman, Jayashree; Olson, John S.] Rice Univ, Dept Biochem & Cell Biol, Houston, TX 77251 USA.
[Soman, Jayashree; Olson, John S.] Rice Univ, WM Keck Ctr Computat Biol, Houston, TX 77251 USA.
[Wulff, Michael] European Synchrotron Radiat Facil, F-38043 Grenoble, France.
RP Anfinrud, PA (reprint author), NIDDK, Chem Phys Lab, NIH, 5 Mem Dr,Bldg 5,Rm 134, Bethesda, MD 20892 USA.
EM anfinrud@nih.gov
FU Robert A. Welch Foundation [C-612]; NIH [HL47020, GM35649]; National
Institute of Diabetes and Digestive and Kidney Diseases, National
Institutes of Health
FX We thank W. A. Eaton and E. Henry for helpful comments, and D. Bourgeois
for sharing his expertise in the analysis of Laue diffraction data. The
time-resolved Laue experiments were performed on the ID09B beamline at
the European Synchrotron Radiation Facility (ESRF), Grenoble, France.
This work was supported by Grants from the Robert A. Welch Foundation
(C-612) and the NIH (HL47020 and GM35649) to J.O., and by the Intramural
Research Program of the National Institute of Diabetes and Digestive and
Kidney Diseases, National Institutes of Health.
NR 38
TC 11
Z9 11
U1 3
U2 24
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0301-0104
J9 CHEM PHYS
JI Chem. Phys.
PD AUG 30
PY 2013
VL 422
SI SI
BP 98
EP 106
DI 10.1016/j.chemphys.2012.12.030
PG 9
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 216UF
UT WOS:000324309600013
PM 24839343
ER
PT J
AU Chung, HS
Cellmer, T
Louis, JM
Eaton, WA
AF Chung, Hoi Sung
Cellmer, Troy
Louis, John M.
Eaton, William A.
TI Measuring ultrafast protein folding rates from photon-by-photon analysis
of single molecule fluorescence trajectories
SO CHEMICAL PHYSICS
LA English
DT Article
DE Single-molecule fluorescence; FRET; Maximum likelihood analysis; Dye
blinking; Ultrafast protein folding rates; Photon trajectories; Villin
subdomain
ID RESONANCE ENERGY-TRANSFER; TRANSITION PATH TIMES; VILLIN HEADPIECE;
SIMULATIONS; SPECTROSCOPY; KINETICS; FRET; SUBDOMAIN; DYNAMICS; STATES
AB Folding and unfolding rates for the ultrafast folding villin subdomain were determined from a photon-by-photon analysis of fluorescence trajectories in single molecule FRET experiments. One of the obstacles to measuring fast kinetics in single molecule fluorescence experiments is blinking of the fluorophores on a timescale that is not well separated from the process of interest. By incorporating acceptor blinking into a two-state kinetics model, we show that it is possible to extract accurate rate coefficients on the microsecond time scale for folding and unfolding using the maximum likelihood method of Gopich and Szabo. This method yields the most likely parameters of a given model that can reproduce the observed photon trajectories. The extracted parameters agree with both the decay rate of the donor-acceptor cross correlation function and the results of ensemble equilibrium and kinetic experiments using nanosecond laser temperature jump. Published by Elsevier B.V.
C1 [Chung, Hoi Sung; Cellmer, Troy; Louis, John M.; Eaton, William A.] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Chung, HS (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM chunghoi@niddk.nih.gov; eaton@helix.nih.gov
RI Chung, Hoi Sung/C-2624-2009
FU NIDDK, NIH
FX This paper is dedicated to Robin M. Hochstrasser, who has produced a
constant stream of pioneering works that have defined the direction of
research in molecular spectroscopy and its applications in biophysics
for over 50 years. We thank Irina Gopich and Attila Szabo for numerous
helpful discussions and Annie Aniana for excellent technical assistance.
This work was supported by the Intramural Research Program of the NIDDK,
NIH.
NR 30
TC 15
Z9 15
U1 1
U2 43
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0301-0104
J9 CHEM PHYS
JI Chem. Phys.
PD AUG 30
PY 2013
VL 422
SI SI
BP 229
EP 237
DI 10.1016/j.chemphys.2012.08.005
PG 9
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 216UF
UT WOS:000324309600027
PM 24443626
ER
PT J
AU Grant, CW
Moran-Paul, CM
Duclos, SK
Guberski, DL
Arreaza-Rubin, G
Spain, LM
AF Grant, Christian W.
Moran-Paul, Catherine M.
Duclos, Shane K.
Guberski, Dennis L.
Arreaza-Rubin, Guillermo
Spain, Lisa M.
TI Testing Agents for Prevention or Reversal of Type 1 Diabetes in Rodents
SO PLOS ONE
LA English
DT Article
ID REGULATORY T-CELLS; MIGRATION INHIBITORY FACTOR; NOD MICE; BB RAT;
AUTOIMMUNE; ANTI-CD3; THERAPY; LISOFYLLINE; REMISSION; DISEASE
AB We report the results of an independent laboratory's tests of novel agents to prevent or reverse type 1 diabetes (T1D) in the non-obese diabetic (NOD) mouse, BioBreeding diabetes prone (BBDP) rat, and multiple autoimmune disease prone (MAD) rat models. Methods were developed to better mimic human clinical trials, including: prescreening, randomization, blinding, and improved glycemic care of the animals. Agents were suggested by the research community in an open call for proposals, and selected for testing by an NIDDK appointed independent review panel. Agents selected for testing to prevent diabetes at later stages of progression in a rodent model were a STAT4 antagonist (DT22669), alpha(1) anti-trypsin (Aralast NP), celastrol (a natural product with anti-inflammatory properties), and a Macrophage Inflammatory Factor inhibitor (ISO-092). Agents tested for reversal of established T1D in rodent models were: alpha(1) anti-trypsin (Aralast NP), tolerogenic peptides (Tregitopes), and a long-acting formulation of GLP-1 (PGC-GLP-1). None of these agents were seen to prevent or reverse type 1 diabetes, while the positive control interventions were effective: anti-CD3 treatment provided disease reversal in the NOD mouse, dexamethasone prevented T1D induction in the MAD rat, and cyclosporin prevented T1D in the BBDP rat. For some tested agents, details of previous formulation, delivery, or dosing, as well as laboratory procedure, availability of reagents and experimental design, could have impacted our ability to confirm prior reports of efficacy in preclinical animal models. In addition, the testing protocols utilized here provided detection of effects in a range commonly used in placebo controlled clinical trials (for example, 50% effect size), and thus may have been underpowered to observe more limited effects. That said, we believe the results compiled here, showing good control and repeatability, confirm the feasibility of screening diverse test agents in an independent laboratory.
C1 [Arreaza-Rubin, Guillermo; Spain, Lisa M.] NIDDK, NIH, Bethesda, MD USA.
[Grant, Christian W.; Moran-Paul, Catherine M.; Duclos, Shane K.; Guberski, Dennis L.] Biomed Res Models BRM Inc, Worcester, MA USA.
[Grant, Christian W.; Moran-Paul, Catherine M.; Duclos, Shane K.; Guberski, Dennis L.] Biomed Res Models BRM Inc, Springfield, MA USA.
RP Spain, LM (reprint author), NIDDK, NIH, Bethesda, MD USA.
EM spainL@niddk.nih.gov
FU National Institutes of Health [N01-DK-62909]
FX This work was funded by the National Institutes of Health under a
contract N01-DK-62909. NIH staff were involved in study design, data
analysis, decision to publish, and preparation of the manuscript.
NR 61
TC 9
Z9 9
U1 0
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 30
PY 2013
VL 8
IS 8
AR e72989
DI 10.1371/journal.pone.0072989
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 211BX
UT WOS:000323880200060
PM 24023664
ER
PT J
AU Westphal, C
Spallek, B
Konkel, A
Marko, L
Qadri, F
DeGraff, LM
Schubert, C
Bradbury, JA
Regitz-Zagrosek, V
Falck, JR
Zeldin, DC
Muller, DN
Schunck, WH
Fischer, R
AF Westphal, Christina
Spallek, Bastian
Konkel, Anne
Marko, Lajos
Qadri, Fatimunnisa
DeGraff, Laura M.
Schubert, Carola
Bradbury, J. Alyce
Regitz-Zagrosek, Vera
Falck, John R.
Zeldin, Darryl C.
Mueller, Dominik N.
Schunck, Wolf-Hagen
Fischer, Robert
TI CYP2J2 Overexpression Protects against Arrhythmia Susceptibility in
Cardiac Hypertrophy
SO PLOS ONE
LA English
DT Article
ID SOLUBLE EPOXIDE HYDROLASE; SENSITIVE K+ CHANNELS; EPOXYEICOSATRIENOIC
ACIDS; ATRIAL-FIBRILLATION; ISCHEMIA/REPERFUSION INJURY; VENTRICULAR
MYOCYTES; PRESSURE-OVERLOAD; MOLECULAR-CLONING; TRANSGENIC MICE;
HEART-FAILURE
AB Maladaptive cardiac hypertrophy predisposes one to arrhythmia and sudden death. Cytochrome P450 (CYP)-derived epoxyeicosatrienoic acids (EETs) promote anti-inflammatory and antiapoptotic mechanisms, and are involved in the regulation of cardiac Ca2+-, K+- and Na+-channels. To test the hypothesis that enhanced cardiac EET biosynthesis counteracts hypertrophy-induced electrical remodeling, male transgenic mice with cardiomyocyte-specific overexpression of the human epoxygenase CYP2J2 (CYP2J2-TG) and wildtype littermates (WT) were subjected to chronic pressure overload (transverse aortic constriction, TAC) or beta-adrenergic stimulation (isoproterenol infusion, ISO). TAC caused progressive mortality that was higher in WT (42% over 8 weeks after TAC), compared to CYP2J2-TG mice (6%). In vivo electrophysiological studies, 4 weeks after TAC, revealed high ventricular tachyarrhythmia inducibility in WT (47% of the stimulation protocols), but not in CYP2J2-TG mice (0%). CYP2J2 overexpression also enhanced ventricular refractoriness and protected against TAC-induced QRS prolongation and delocalization of left ventricular connexin-43. ISO for 14 days induced high vulnerability for atrial fibrillation in WT mice (54%) that was reduced in CYP-TG mice (17%). CYP2J2 overexpression also protected against ISO-induced reduction of atrial refractoriness and development of atrial fibrosis. In contrast to these profound effects on electrical remodeling, CYP2J2 overexpression only moderately reduced TAC-induced cardiac hypertrophy and did not affect the hypertrophic response to beta-adrenergic stimulation. These results demonstrate that enhanced cardiac EET biosynthesis protects against electrical remodeling, ventricular tachyarrhythmia, and atrial fibrillation susceptibility during maladaptive cardiac hypertrophy.
C1 [Westphal, Christina; Konkel, Anne; Mueller, Dominik N.; Schunck, Wolf-Hagen] Max Delbruck Ctr Mol Med, Berlin, Germany.
[Spallek, Bastian; Marko, Lajos; Qadri, Fatimunnisa; Mueller, Dominik N.] Expt & Clin Res Ctr, Berlin, Germany.
[DeGraff, Laura M.; Bradbury, J. Alyce; Zeldin, Darryl C.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
[Schubert, Carola; Regitz-Zagrosek, Vera] Charite, Inst Gender Med, D-13353 Berlin, Germany.
[Falck, John R.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Mueller, Dominik N.] Univ Erlangen Nurnberg, Nikolaus Fiebiger Ctr Mol Med, Dept Expt Med 1, Nurnberg, Germany.
[Fischer, Robert] Charite, Clin Cardiol & Pulmonol, D-13353 Berlin, Germany.
RP Schunck, WH (reprint author), Max Delbruck Ctr Mol Med, Berlin, Germany.
EM schunck@mdc-berlin.de
OI Marko, Lajos/0000-0003-1888-5575; Falck, John/0000-0002-9219-7845
FU Deutsche Forschungsgemeinschaft, (DFG) [Schu822/5, FOR 1054];
PreGoBio-Program of the MDC; German Competence Network Heart Failure;
Intramural Research Division of the NIH; National Institute of
Environmental Health Sciences [Z01 ES025034]; NIH [GM31278]; Robert A.
Welch Foundation [GL625910]
FX This work was supported by a grant from the Deutsche
Forschungsgemeinschaft, (DFG); Schu822/5; FOR 1054. CW received a grant
from the PreGoBio-Program of the MDC and BS from the German Competence
Network Heart Failure. This work was also supported, in part, by the
Intramural Research Division of the NIH, National Institute of
Environmental Health Sciences (Z01 ES025034), NIH GM31278 and the Robert
A. Welch Foundation (GL625910). The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 40
TC 11
Z9 12
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 AUG 30
PY 2013
VL 8
IS 8
AR e73490
DI 10.1371/journal.pone.0073490
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 211BX
UT WOS:000323880200081
PM 24023684
ER
PT J
AU Moslehi, R
Mills, JL
Signore, C
Kumar, A
Ambroggio, X
Dzutsev, A
AF Moslehi, Roxana
Mills, James L.
Signore, Caroline
Kumar, Anil
Ambroggio, Xavier
Dzutsev, Amiran
TI Integrative transcriptome analysis reveals dysregulation of canonical
cancer molecular pathways in placenta leading to preeclampsia
SO SCIENTIFIC REPORTS
LA English
DT Article
ID PROTEIN-INTERACTION NETWORKS; EPIDERMAL-GROWTH-FACTOR; GENE-EXPRESSION;
DNA-REPAIR; TRICHOTHIODYSTROPHY; CELLS; ATF3; TROPHOBLASTS; APOPTOSIS;
DISORDER
AB We previously suggested links between specific XPD mutations in the fetal genome and the risk of placental maldevelopment and preeclampsia, possibly due to impairment of Transcription Factor (TF) IIH-mediated functions in placenta. To identify the underlying mechanisms, we conducted the current integrative analysis of several relevant transcriptome data sources. Our meta-analysis revealed downregulation of TFIIH subunits in preeclamptic placentas. Our overall integrative analysis suggested that, in the presence of hypoxia and oxidative stress, EGFR signaling deficiency, which can be caused by TFIIH impairment as well as by other mechanisms, results in ATF3 upregulation, inducing mediators of clinical symptoms of preeclampsia such as FLT1 and ENG. EGFR- and ATF3-dependent pathways play prominent roles in cancer development. We propose that dysregulation of these canonical cancer molecular pathways occurs in preeclampsia and delineate the relevance of TFIIH, providing etiologic clues which could eventually translate into a therapeutic approach.
C1 [Moslehi, Roxana; Kumar, Anil] SUNY Albany, Sch Publ Hlth, Dept Epidemiol & Biostat, Albany, NY 12144 USA.
[Moslehi, Roxana] SUNY Albany, Canc Res Ctr, Albany, NY 12144 USA.
[Mills, James L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH,DHHS, Bethesda, MD 20892 USA.
[Signore, Caroline] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, Ctr Dev Biol & Perinatal Med, NIH,DHHS, Bethesda, MD 20892 USA.
[Ambroggio, Xavier] NIAID, Bioinformat & Computat Biosci Branch, NIH, Bethesda, MD 20814 USA.
[Dzutsev, Amiran] Sci Applicat Int Corp SAIC Frederick Inc, Frederick Natl Lab, Frederick, MD 21702 USA.
[Dzutsev, Amiran] NCI, Canc Inflammat Program, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
RP Moslehi, R (reprint author), SUNY Albany, Sch Publ Hlth, Dept Epidemiol & Biostat, Albany, NY 12144 USA.
EM rmoslehi@albany.edu
FU Center for Social and Demographic Analysis (CSDA) at the University at
Albany from NICHD [R24 HD044943]; Intramural Research Program-NICHD, NIH
FX The authors thank Dr. AR Lehmann at University of Sussex and Dr. M
Hubank at University College, London for providing the XPDTTD
gene expression dataset, Dr. A. Morgun at Oregon State University for
advice on microarray data analysis, and Dr. V. Nagarajan at National
Institute of Allergy and Infectious Diseases (NIAID), NIH for critically
reviewing the methods and conclusions of the paper. Technical support
provided by Mr. H. Martinez at University at Albany throughout the study
has been invaluable. This study was supported in part by a grant to the
Center for Social and Demographic Analysis (CSDA) at the University at
Albany from NICHD; (R24 HD044943) and a research award to RM from CSDA.
This research was also supported by the Intramural Research
Program-NICHD, NIH. Opinions, findings and conclusions expressed here
are those of the authors and do not necessarily reflect the views of the
funding agencies.
NR 52
TC 12
Z9 12
U1 1
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 AUG 30
PY 2013
VL 3
AR 2407
DI 10.1038/srep02407
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 208QW
UT WOS:000323695200001
PM 23989136
ER
PT J
AU Tian, AL
Qi, J
Liu, YT
Wang, FK
Ito, Y
Wei, Y
AF Tian, Ailin
Qi, Jing
Liu, Yating
Wang, Fengkang
Ito, Yoichiro
Wei, Yun
TI Chiral magnetic microspheres purified by centrifugal field flow
fractionation and microspheres magnetic chiral chromatography for
benzoin racemate separation
SO JOURNAL OF CHROMATOGRAPHY A
LA English
DT Article
DE Chiral magnetic microspheres; Centrifugal field flow fractionation;
Microspheres magnetic chrial chromatography; Benzoin racemate
ID PERFORMANCE LIQUID-CHROMATOGRAPHY; IRON-OXIDE NANOPARTICLES;
BETA-CYCLODEXTRIN; STATIONARY PHASES; NANOCRYSTALS; GOLD;
ELECTROPHORESIS; SELECTOR; SHAPE; GEL
AB Separation of enantiomers still remains a challenge due to their identical physical and chemical properties in a chiral environment, and the research on specific chiral selector along with separation techniques continues to be conducted to resolve individual enantiomers. In our laboratory the promising magnetic chiral microspheres Fe3O4@SiO2@cellulose-2, 3-bis (3,5-dimethylphenylcarbamate) have been developed to facilitate the resolution using both its magnetic property and chiral recognition ability. In our present studies this magnetic chiral selector was first purified by centrifuge field flow fractionation, and then used to separate benzoin racemate by a chromatographic method. Uniform-sized and masking-impurity-removed magnetic chiral selector was first obtained by field flow fractionation with ethanol through a spiral column mounted on the type-J planetary centrifuge, and using the purified magnetic chiral selector, the final chromatographic separation of benzoin racemate was successfully performed by eluting with ethanol through a coiled tube (wound around the cylindrical magnet to retain the magnetic chiral selector as a stationary phase) submerged in dry ice. In addition, an external magnetic field facilitates the recycling of the magnetic chiral selector. (C) 2013 Elsevier B.V. All rights reserved.
C1 [Tian, Ailin; Qi, Jing; Liu, Yating; Wang, Fengkang; Wei, Yun] Beijing Univ Chem Technol, State Key Lab Chem Resource Engn, Beijing 100029, Peoples R China.
[Ito, Yoichiro; Wei, Yun] NHLBI, Lab Bioseparat Technol, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA.
RP Wei, Y (reprint author), Beijing Univ Chem Technol, State Key Lab Chem Resource Engn, 15 Beisanhuan East Rd, Beijing 100029, Peoples R China.
EM weiyun@mail.buct.edu.cn
FU National Natural Science Foundation of China (NSFC) [21075007]; Program
for New Century Excellent Talents in University [NCET-11-0563]; Special
Fund for Agro-scientific Research in the Public Interest [200803022,
201103027]; Program for Changjiang Scholars and Innovative Research Team
in University [PCSIRT1205]
FX The research work was supported from the National Natural Science
Foundation of China (NSFC, Grant No. 21075007), Program for New Century
Excellent Talents in University (NCET-11-0563), Special Fund for
Agro-scientific Research in the Public Interest (project 200803022 &
201103027) and Program for Changjiang Scholars and Innovative Research
Team in University (PCSIRT1205).
NR 25
TC 1
Z9 1
U1 4
U2 48
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0021-9673
J9 J CHROMATOGR A
JI J. Chromatogr. A
PD AUG 30
PY 2013
VL 1305
BP 333
EP 337
DI 10.1016/j.chroma.2013.07.044
PG 5
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 204JS
UT WOS:000323362200041
PM 23891368
ER
PT J
AU Guyard, C
Raffel, SJ
Schrumpf, ME
Dahlstrom, E
Sturdevant, D
Ricklefs, SM
Martens, C
Hayes, SF
Fischer, ER
Hansen, BT
Porcella, SF
Schwan, TG
AF Guyard, Cyril
Raffel, Sandra J.
Schrumpf, Merry E.
Dahlstrom, Eric
Sturdevant, Daniel
Ricklefs, Stacy M.
Martens, Craig
Hayes, Stanley F.
Fischer, Elizabeth R.
Hansen, Bryan T.
Porcella, Stephen F.
Schwan, Tom G.
TI Periplasmic Flagellar Export Apparatus Protein, FliH, Is Involved in
Post-Transcriptional Regulation of FlaB, Motility and Virulence of the
Relapsing Fever Spirochete Borrelia hermsii
SO PLOS ONE
LA English
DT Article
ID LYME-DISEASE; SERPULINA-HYODYSENTERIAE; MURINE MODEL; LESS MUTANT;
BURGDORFERI; SALMONELLA; GENE; CHEMOTAXIS; INACTIVATION; EXPRESSION
AB Spirochetes are bacteria characterized in part by rotating periplasmic flagella that impart their helical or flat-wave morphology and motility. While most other bacteria rely on a transcriptional cascade to regulate the expression of motility genes, spirochetes employ post-transcriptional mechanism(s) that are only partially known. In the present study, we characterize a spontaneous non-motile mutant of the relapsing fever spirochete Borrelia hermsii that was straight, nonmotile and deficient in periplasmic flagella. We used next generation DNA sequencing of the mutant's genome, which when compared to the wild-type genome identified a 142 bp deletion in the chromosomal gene encoding the flagellar export apparatus protein FliH. Immunoblot and transcription analyses showed that the mutant phenotype was linked to the posttranscriptional deficiency in the synthesis of the major periplasmic flagellar filament core protein FlaB. Despite the lack of FlaB, the amount of FlaA produced by the fliH mutant was similar to the wild-type level. The turnover of the residual pool of FlaB produced by the fliH mutant was comparable to the wild-type spirochete. The non-motile mutant was not infectious in mice and its inoculation did not induce an antibody response. Trans-complementation of the mutant with an intact fliH gene restored the synthesis of FlaB, a normal morphology, motility and infectivity in mice. Therefore, we propose that the flagellar export apparatus protein regulates motility of B. hermsii at the post-transcriptional level by influencing the synthesis of FlaB.
C1 [Guyard, Cyril] Publ Hlth Ontario, Toronto, ON, Canada.
[Guyard, Cyril] Univ Toronto, Toronto, ON, Canada.
[Guyard, Cyril] Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada.
[Raffel, Sandra J.; Schrumpf, Merry E.; Schwan, Tom G.] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT USA.
[Dahlstrom, Eric; Sturdevant, Daniel; Ricklefs, Stacy M.; Martens, Craig; Hayes, Stanley F.; Fischer, Elizabeth R.; Hansen, Bryan T.; Porcella, Stephen F.] NIAID, Res Technol Sect, Res Technol Branch, Rocky Mt Labs,NIH, Hamilton, MT USA.
RP Guyard, C (reprint author), Publ Hlth Ontario, Toronto, ON, Canada.
EM cyril.guyard@gmail.com
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases (NIAID) of the National Institutes of Health (NIH),
USA; Public Health Ontario
FX This work was supported by the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases (NIAID) of the National
Institutes of Health (NIH), USA (http://www.niaid.nih.gov/). CG is
supported by Public Health Ontario (http://www.oahpp.ca/). The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 70
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 AUG 29
PY 2013
VL 8
IS 8
AR e72550
DI 10.1371/journal.pone.0072550
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 209DO
UT WOS:000323734600028
PM 24009690
ER
PT J
AU Hudson, RS
Yi, M
Esposito, D
Glynn, SA
Starks, AM
Yang, Y
Schetter, AJ
Watkins, SK
Hurwitz, AA
Dorsey, TH
Stephens, RM
Croce, CM
Ambs, S
AF Hudson, R. S.
Yi, M.
Esposito, D.
Glynn, S. A.
Starks, A. M.
Yang, Y.
Schetter, A. J.
Watkins, S. K.
Hurwitz, A. A.
Dorsey, T. H.
Stephens, R. M.
Croce, C. M.
Ambs, S.
TI MicroRNA-106b-25 cluster expression is associated with early disease
recurrence and targets caspase-7 and focal adhesion in human prostate
cancer
SO ONCOGENE
LA English
DT Article
DE prostate cancer; microRNA; apoptosis; disease outcome
ID BREAST-CANCER; MICRORNAS; PROGRESSION; APOPTOSIS; LEUKEMIA; GENES;
OVEREXPRESSION; CARCINOMA; PROFILE; FAMILY
AB The miR-106b-25 microRNA (miRNA) cluster is a candidate oncogene in human prostate cancer. Here, we report that miRNAs encoded by miR-106b-25 are upregulated in both primary tumors and distant metastasis. Moreover, increased tumor miR-106b expression was associated with disease recurrence and the combination of high miR-106b and low CASP7 (caspase-7) expressions in primary tumors was an independent predictor of early disease recurrence (adjusted hazard ratio = 4.1; 95% confidence interval: 1.6-12.3). To identify yet unknown oncogenic functions of miR-106b, we overexpressed it in LNCaP human prostate cancer cells to examine miR-106b-induced global expression changes among protein-coding genes. The approach revealed that CASP7 is a direct target of miR-106b, which was confirmed by western blot analysis and a 3'-untranslated region reporter assay. Moreover, selected phenotypes induced by miR-106b knockdown in DU145 human prostate cancer cells did not develop when both miR-106b and CASP7 expression were inhibited. Further analyses showed that CASP7 is downregulated in primary prostate tumors and metastatic lesions across multiple data sets and is by itself associated with disease recurrence and disease-specific survival. Using bioinformatics, we also observed that miR-106b-25 may specifically influence focal adhesion-related pathways. This observation was experimentally examined using miR-106b-25-transduced 22Rv1 human prostate cancer cells. After infection with a miR-106b-25 lentiviral expression construct, 22Rv1 cells showed increased adhesion to basement membrane-and bone matrix-related filaments and enhanced soft agar growth. In summary, miR-106b-25 was found to be associated with prostate cancer progression and disease outcome and may do so by altering apoptosis-and focal adhesion-related pathways.
C1 [Hudson, R. S.; Glynn, S. A.; Starks, A. M.; Yang, Y.; Schetter, A. J.; Dorsey, T. H.; Ambs, S.] NCI, Human Carcinogenesis Lab, Ctr Canc Res CRC, NIH, Bethesda, MD 20892 USA.
[Yi, M.; Stephens, R. M.] NCI, Adv Biomed Comp Ctr, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Esposito, D.] NCI, Protein Express Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Watkins, S. K.; Hurwitz, A. A.] NCI, Mol Immunoregulat Lab, Frederick, MD 21701 USA.
[Croce, C. M.] Ohio State Univ, Ctr Comprehens Canc, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA.
RP Ambs, S (reprint author), NCI, Human Carcinogenesis Lab, Ctr Canc Res CRC, Bldg 37 Room 3050B, Bethesda, MD 20892 USA.
EM ambss@mail.nih.gov
RI Glynn, Sharon/D-7136-2013
OI Glynn, Sharon/0000-0003-1459-2580
FU NIH, National Cancer Institute, Center for Cancer Research
FX We thank Barbara J Taylor at the NCI FACS Core Laboratory for technical
help. This research was supported by the Intramural Research Program of
the NIH, National Cancer Institute, Center for Cancer Research.
NR 35
TC 39
Z9 42
U1 0
U2 15
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD AUG 29
PY 2013
VL 32
IS 35
BP 4139
EP 4147
DI 10.1038/onc.2012.424
PG 9
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 209IG
UT WOS:000323748500009
PM 22986525
ER
PT J
AU Ben Isaac, E
Manor, U
Kachar, B
Yochelis, A
Gov, NS
AF Ben Isaac, Eyal
Manor, Uri
Kachar, Bechara
Yochelis, Arik
Gov, Nir S.
TI Linking actin networks and cell membrane via a
reaction-diffusion-elastic description of nonlinear filopodia initiation
SO PHYSICAL REVIEW E
LA English
DT Article
ID DISSIPATIVE SYSTEMS; DENDRITIC NETWORK; LIPID-BILAYERS; ARP2/3 COMPLEX;
MYOSIN-X; MECHANICS; PROTEINS; DYNAMICS; BUNDLES; TIPS
AB Reaction-diffusion models have been used to describe pattern formation on the cellular scale, and traditionally do not include feedback between cellular shape changes and biochemical reactions. We introduce here a distinct reaction-diffusion-elasticity approach: The reaction-diffusion part describes bistability between two actin orientations, coupled to the elastic energy of the cell membrane deformations. This coupling supports spatially localized patterns, even when such solutions do not exist in the uncoupled self-inhibited reaction-diffusion system. We apply this concept to describe the nonlinear (threshold driven) initiation mechanism of actin-based cellular protrusions and provide support by several experimental observations.
C1 [Ben Isaac, Eyal; Gov, Nir S.] Weizmann Inst Sci, Dept Chem Phys, IL-76100 Rehovot, Israel.
[Manor, Uri; Kachar, Bechara] Natl Inst Deafness & Other Commun Disorders, Lab Cell Struct & Dynam, NIH, Bethesda, MD 20892 USA.
[Yochelis, Arik] Ben Gurion Univ Negev, Jacob Blaustein Inst Desert Res BIDR, Swiss Inst Dryland Environm & Energy Res, Dept Solar Energy & Environm Phys, IL-84990 Midreshet Ben Gurion, Israel.
[Yochelis, Arik] Ben Gurion Univ Negev, Jacob Blaustein Inst Desert Res BIDR, Swiss Inst Dryland Environm & Energy Res, Ben Gurion Natl Solar Energy Ctr, IL-84990 Midreshet Ben Gurion, Israel.
RP Ben Isaac, E (reprint author), Weizmann Inst Sci, Dept Chem Phys, IL-76100 Rehovot, Israel.
EM eyalbi@weizmann.ac.il; yochelis@bgu.ac.il; nir.gov@weizmann.ac.il
RI Yochelis, Arik/C-6782-2013
OI Yochelis, Arik/0000-0002-1516-0766
NR 59
TC 1
Z9 1
U1 0
U2 20
PU AMER PHYSICAL SOC
PI COLLEGE PK
PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA
SN 1539-3755
J9 PHYS REV E
JI Phys. Rev. E
PD AUG 29
PY 2013
VL 88
IS 2
AR 022718
DI 10.1103/PhysRevE.88.022718
PG 10
WC Physics, Fluids & Plasmas; Physics, Mathematical
SC Physics
GA 208XD
UT WOS:000323714600006
PM 24032875
ER
PT J
AU Parker, J
Sherman, E
van de Raa, M
van der Meer, D
Samelson, LE
Losert, W
AF Parker, Joshua
Sherman, Eilon
van de Raa, Matthias
van der Meer, Devaraj
Samelson, Lawrence E.
Losert, Wolfgang
TI Automatic sorting of point pattern sets using Minkowski functionals
SO PHYSICAL REVIEW E
LA English
DT Article
ID MORPHOLOGY; CLUSTERS; ANTIGEN; MODEL
AB Point pattern sets arise in many different areas of physical, biological, and applied research, representing many random realizations of underlying pattern formation mechanisms. These pattern sets can be heterogeneous with respect to underlying spatial processes, which may not be visually distiguishable. This heterogeneity can be elucidated by looking at statistical measures of the patterns sets and using these measures to divide the pattern sets into distinct groups representing like spatial processes. We introduce here a numerical procedure for sorting point pattern sets into spatially homogenous groups using functional principal component analysis (FPCA) applied to the approximated Minkowski functionals of each pattern. We demonstrate that this procedure correctly sorts pattern sets into similar groups both when the patterns are drawn from similar processes and when the second-order characteristics of the pattern are identical. We highlight this routine for distinguishing the molecular patterning of fluorescently labeled cell membrane proteins, a subject of much interest in studies investigating complex spatial signaling patterns involved in the human immune response.
C1 [Parker, Joshua; Losert, Wolfgang] Univ Maryland, Dept Phys, College Pk, MD 20740 USA.
[Sherman, Eilon] Hebrew Univ Jerusalem, Racah Inst Phys, IL-91904 Jerusalem, Israel.
[van de Raa, Matthias; van der Meer, Devaraj] Univ Twente, MESA, Phys Fluids Grp, NL-7500 AE Enschede, Netherlands.
[van de Raa, Matthias; van der Meer, Devaraj] Univ Twente, Inst Nanotechnol, NL-7500 AE Enschede, Netherlands.
[van de Raa, Matthias; van der Meer, Devaraj] Univ Twente, JM Burgers Ctr Fluid Dynam, NL-7500 AE Enschede, Netherlands.
[Samelson, Lawrence E.] NIH, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Parker, J (reprint author), Univ Maryland, Dept Phys, College Pk, MD 20740 USA.
EM jmparker@umd.edu
RI Sherman, Eilon /B-3688-2014
OI Sherman, Eilon /0000-0002-7403-6036
FU National Cancer Institute (The Center for Cancer Research); NIH
[GM085574]
FX The authors would like to thank Detlef Lohse for suggesting Minkowski
functional analysis and Can Guven and Mark Herrera for their helpful
advice during this project. This research was supported in part (L E.S.)
by the Intramural Research Programs of the National Cancer Institute
(The Center for Cancer Research) and by NIH Grant No. GM085574 (W.L.).
NR 30
TC 2
Z9 2
U1 0
U2 7
PU AMER PHYSICAL SOC
PI COLLEGE PK
PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA
SN 2470-0045
EI 2470-0053
J9 PHYS REV E
JI Phys. Rev. E
PD AUG 29
PY 2013
VL 88
IS 2
AR 022720
DI 10.1103/PhysRevE.88.022720
PG 8
WC Physics, Fluids & Plasmas; Physics, Mathematical
SC Physics
GA 208XD
UT WOS:000323714600008
PM 24032877
ER
PT J
AU De, S
Zhang, YQ
Wolkow, CA
Zou, SG
Goldberg, I
Becker, KG
AF De, Supriyo
Zhang, Yongqing
Wolkow, Catherine A.
Zou, Sige
Goldberg, Ilya
Becker, Kevin G.
TI Genome-wide modeling of complex phenotypes in Caenorhabditis elegans and
Drosophila melanogaster
SO BMC GENOMICS
LA English
DT Article
DE C. elegans; D. melanogaster; Worm; Fly; Aging; Gene set; Phenotype;
Ontology; Network; Gene expression
ID GENE SET ENRICHMENT; EXPRESSION; ASSOCIATION; PROFILES; ONTOLOGY;
DISEASE; MOUSE
AB Background: The genetic and molecular basis for many intermediate and end stage phenotypes in model systems such as C. elegans and D. melanogaster has long been known to involve pleiotropic effects and complex multigenic interactions. Gene sets are groups of genes that contribute to multiple biological or molecular phenomena. They have been used in the analysis of large molecular datasets such as microarray data, Next Generation sequencing, and other genomic datasets to reveal pleiotropic and multigenic contributions to phenotypic outcomes. Many model systems lack species specific organized phenotype based gene sets to enable high throughput analysis of large molecular datasets.
Results and discussion: Here, we describe two novel collections of gene sets in C. elegans and D. melanogaster that are based exclusively on genetically determined phenotypes and use a controlled phenotypic ontology. We use these collections to build genome-wide models of thousands of defined phenotypes in both model species. In addition, we demonstrate the utility of these gene sets in systems analysis and in analysis of gene expression-based molecular datasets and show how they are useful in analysis of genomic datasets connecting multigenic gene inputs to complex phenotypes.
Conclusions: Phenotypic based gene sets in both C. elegans and D. melanogaster are developed, characterized, and shown to be useful in the analysis of large scale species-specific genomic datasets. These phenotypic gene set collections will contribute to the understanding of complex phenotypic outcomes in these model systems.
C1 [De, Supriyo; Zhang, Yongqing; Becker, Kevin G.] NIA, Gene Express & Genom Unit, Genet Lab, NIH,Biomed Res Ctr, Baltimore, MD 21224 USA.
[Wolkow, Catherine A.] Albert Einstein Coll Med, Dept Neurosci, Bronx, NY 10461 USA.
[Zou, Sige] NIA, Translat Gerontol Branch, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA.
[Goldberg, Ilya] NIA, Image Informat & Computat Biol Unit, Genet Lab, NIH,Biomed Res Ctr, Baltimore, MD 21224 USA.
RP Becker, KG (reprint author), NIA, Gene Express & Genom Unit, Genet Lab, NIH,Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM beckerk@grc.nia.nih.gov
RI Goldberg, Ilya/H-5307-2011;
OI Goldberg, Ilya/0000-0001-8514-6110; De, Supriyo/0000-0002-2075-7655;
Becker, Kevin/0000-0002-6794-6656
FU Intramural Research Program of the NIH, National Institute on Aging
FX The authors would like to thank Gary Schindelman and Paul Sternberg from
WormBase for providing gene-phenotype files and Dr Elin Lehrmann for
critical reading of the manuscript. This research was supported entirely
by the Intramural Research Program of the NIH, National Institute on
Aging.
NR 19
TC 1
Z9 1
U1 0
U2 9
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 AUG 28
PY 2013
VL 14
AR 580
DI 10.1186/1471-2164-14-580
PG 13
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 227KN
UT WOS:000325111700001
PM 23984798
ER
PT J
AU He, YQ
Gong, L
Fang, YP
Zhan, Q
Liu, HX
Lu, YL
Guo, GL
Lehman-McKeeman, L
Fang, JW
Wan, YJY
AF He, Yuqi
Gong, Lei
Fang, Yaping
Zhan, Qi
Liu, Hui-Xin
Lu, Yanliu
Guo, Grace L.
Lehman-McKeeman, Lois
Fang, Jianwen
Wan, Yu-Jui Yvonne
TI The role of retinoic acid in hepatic lipid homeostasis defined by
genomic binding and transcriptome profiling
SO BMC GENOMICS
LA English
DT Article
DE Nuclear receptor; Retinoids x receptor; Retinoic acid receptor;
Farnesnoid x receptor; Peroxisomal; proliferator-activated receptor a;
Liver x receptor; Pregnane x receptor; Chromatin immunoprecipitation;
Sequencing; Microarray
ID X-RECEPTOR-ALPHA; HEPATOCYTE RXR-ALPHA; MOUSE-LIVER; MEDIATED PATHWAYS;
NUCLEAR RECEPTOR; DEFICIENT MICE; EXPRESSION; METABOLISM;
PHOSPHATIDYLETHANOLAMINE; PHOSPHATIDYLCHOLINE
AB Background: The eyes and skin are obvious retinoid target organs. Vitamin A deficiency causes night blindness and retinoids are widely used to treat acne and psoriasis. However, more than 90% of total body retinol is stored in liver stellate cells. In addition, hepatocytes produce the largest amount of retinol binding protein and cellular retinoic acid binding protein to mobilize retinol from the hepatic storage pool and deliver retinol to its receptors, respectively. Furthermore, hepatocytes express the highest amount of retinoid x receptor alpha (RXRa) among all the cell types. Surprisingly, the function of endogenous retinoids in the liver has received very little attention.
Results: Based on the data generated from chromatin immunoprecipitation followed by sequencing, the global DNA binding of transcription factors including retinoid x receptor a (RXRa) along with its partners i.e. retinoic acid receptor a (RARa), pregnane x receptor (PXR), liver x receptor (LXR), farnesoid x receptor (FXR), and peroxisome proliferator-activated receptor a (PPARa) has been established. Based on the binding, functional annotation illustrated the role of those receptors in regulating hepatic lipid homeostasis. To correlate the DNA binding data with gene expression data, the expression patterns of 576 genes that regulate lipid homeostasis were studied in wild type and liver RXRa-null mice treated with and without RA. The data showed that RA treatment and RXRa-deficiency had opposite effects in regulating lipid homeostasis. A subset of genes (114), which could clearly differentiate the effect of ligand treatment and receptor deficiency, were selected for further functional analysis. The expression data suggested that RA treatment could produce unsaturated fatty acids and induce triglyceride breakdown, bile acid secretion, lipolysis, and retinoids elimination. In contrast, RXRa deficiency might induce the synthesis of saturated fatty acids, triglyceride, cholesterol, bile acids, and retinoids. In addition, DNA binding data indicated extensive cross-talk among RARa, PXR, LXR, FXR, and PPARa in regulating those RA/RXRa-dependent gene expression levels. Moreover, RA reduced serum cholesterol, triglyceride, and bile acid levels in mice.
Conclusions: We have characterized the role of hepatic RA for the first time. Hepatic RA mediated through RXRa and its partners regulates lipid homeostasis.
C1 [He, Yuqi; Liu, Hui-Xin; Lu, Yanliu; Wan, Yu-Jui Yvonne] Univ Calif Davis, Davis Hlth Syst, Dept Med Pathol & Lab Med, Sacramento, CA 95817 USA.
[Gong, Lei; Lehman-McKeeman, Lois] Bristol Myers Squibb Co, Discovery Toxicol, Princeton, NJ 08543 USA.
[Fang, Yaping] Univ Kansas, Appl Bioinformat Lab, Lawrence, KS 66045 USA.
[Zhan, Qi] Guangzhou Med Univ, Municipal Peoples Hosp Guangzhou 1, Dept Gastroenterol Hepatol, Guangzhou 510180, Guangdong, Peoples R China.
[Guo, Grace L.] Rutgers State Univ, Dept Pharmacol & Toxicol, Ernest Mario Sch Pharm, Piscataway, NJ 08854 USA.
[Fang, Jianwen] NCI, Biometr Res Branch, Rockville, MD 20850 USA.
RP Wan, YJY (reprint author), Univ Calif Davis, Davis Hlth Syst, Dept Med Pathol & Lab Med, Sacramento, CA 95817 USA.
EM yjywan@ucdavis.edu
OI Fang, Yaping/0000-0001-6075-0768
FU NCI NIH HHS [P30 CA093373]; NIDDK NIH HHS [R01 DK092100]; NIGMS NIH HHS
[R01 GM104037]
NR 34
TC 8
Z9 8
U1 1
U2 20
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD AUG 28
PY 2013
VL 14
AR 575
DI 10.1186/1471-2164-14-575
PG 11
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 215KY
UT WOS:000324210000001
PM 23981290
ER
PT J
AU Sarai, N
Nimura, K
Tamura, T
Kanno, T
Patel, MC
Heightman, TD
Ura, K
Ozato, K
AF Sarai, Naoyuki
Nimura, Keisuke
Tamura, Tomohiko
Kanno, Tomohiko
Patel, Mira C.
Heightman, Tom D.
Ura, Kiyoe
Ozato, Keiko
TI WHSC1 links transcription elongation to HIRA-mediated histone H3.3
deposition
SO EMBO JOURNAL
LA English
DT Article
DE BRD4; HIRA; histone H3.3 exchange; transcription elongation; WHSC1
ID RNA-POLYMERASE-II; BROMODOMAIN PROTEIN BRD4; WOLF-HIRSCHHORN-SYNDROME;
INTERFERON-STIMULATED GENES; P-TEFB; VARIANT H3.3; LYSINE 36;
MULTIPLE-MYELOMA; SET2 METHYLATION; NUCLEAR RECEPTOR
AB Actively transcribed genes are enriched with the histone variant H3.3. Although H3.3 deposition has been linked to transcription, mechanisms controlling this process remain elusive. We investigated the role of the histone methyltransferase Wolf-Hirschhorn syndrome candidate 1 (WHSC1) (NSD2/MMSET) in H3.3 deposition into interferon (IFN) response genes. IFN treatment triggered robust H3.3 incorporation into activated genes, which continued even after cessation of transcription. Likewise, UV radiation caused H3.3 deposition in UV-activated genes. However, in Whsc1(-/-) cells IFN- or UV-triggered H3.3 deposition was absent, along with a marked reduction in IFN- or UV-induced transcription. We found that WHSC1 interacted with the bromodomain protein 4 (BRD4) and the positive transcription elongation factor b (P-TEFb) and facilitated transcriptional elongation. WHSC1 also associated with HIRA, the H3.3-specific histone chaperone, independent of BRD4 and P-TEFb. WHSC1 and HIRA co-occupied IFN-stimulated genes and supported prolonged H3.3 incorporation, leaving a lasting transcriptional mark. Our results reveal a previously unrecognized role of WHSC1, which links transcriptional elongation and H3.3 deposition into activated genes through two molecularly distinct pathways.
C1 [Sarai, Naoyuki; Kanno, Tomohiko; Patel, Mira C.; Ozato, Keiko] NICHHD, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
[Nimura, Keisuke; Ura, Kiyoe] Osaka Univ, Grad Sch Med, Div Gene Therapy Sci, Osaka, Japan.
[Tamura, Tomohiko] Yokohama City Univ, Grad Sch Med, Dept Immunol, Yokohama, Kanagawa, Japan.
[Heightman, Tom D.] Univ Oxford, Struct Genom Consortium, Oxford, England.
[Ura, Kiyoe] Japan Sci & Technol Agcy, PRESTO, Saitama, Japan.
RP Ozato, K (reprint author), NICHHD, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
EM ozatok@dir6.nichd.nih.gov
RI Patel, Mira/A-3013-2015
FU NICHD; NIH Intramural AIDS Targeted Antiviral Program, National
Institutes of Health; NIH-Japan Society for Promotion of Science (JSPS)
Fellowship
FX We thank Drs D Singer, K Zhao, and J Zhu for critical reading of the
manuscript; Mr W Huynh, Drs A Dey, and H Kurumizaka for advice on
experiments. This work was supported by the Intramural Program of NICHD
and the NIH Intramural AIDS Targeted Antiviral Program, National
Institutes of Health. NS was partially supported by the NIH-Japan
Society for Promotion of Science (JSPS) Fellowship.
NR 72
TC 15
Z9 15
U1 0
U2 11
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0261-4189
J9 EMBO J
JI Embo J.
PD AUG 28
PY 2013
VL 32
IS 17
BP 2392
EP 2406
DI 10.1038/emboj.2013.176
PG 15
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 209LM
UT WOS:000323758300009
PM 23921552
ER
PT J
AU Osinusi, A
Meissner, EG
Lee, YJ
Bon, D
Heytens, L
Nelson, A
Sneller, M
Kohli, A
Barrett, L
Proschan, M
Herrmann, E
Shivakumar, B
Gu, WJ
Kwan, R
Teferi, G
Talwani, R
Silk, R
Kotb, C
Wroblewski, S
Fishbein, D
Dewar, R
Highbarger, H
Zhang, X
Kleiner, D
Wood, BJ
Chavez, J
Symonds, WT
Subramanian, M
McHutchison, J
Polis, MA
Fauci, AS
Masur, H
Kottilil, S
AF Osinusi, Anuoluwapo
Meissner, Eric G.
Lee, Yu-Jin
Bon, Dimitra
Heytens, Laura
Nelson, Amy
Sneller, Michael
Kohli, Anita
Barrett, Lisa
Proschan, Michael
Herrmann, Eva
Shivakumar, Bhavana
Gu, Wenjuan
Kwan, Richard
Teferi, Geb
Talwani, Rohit
Silk, Rachel
Kotb, Colleen
Wroblewski, Susan
Fishbein, Dawn
Dewar, Robin
Highbarger, Helene
Zhang, Xiao
Kleiner, David
Wood, Brad J.
Chavez, Jose
Symonds, William T.
Subramanian, Mani
McHutchison, John
Polis, Michael A.
Fauci, Anthony S.
Masur, Henry
Kottilil, Shyamasundaran
TI Sofosbuvir and Ribavirin for Hepatitis C Genotype 1 in Patients With
Unfavorable Treatment Characteristics A Randomized Clinical Trial
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID UNITED-STATES; VIRUS-INFECTION; PLUS RIBAVIRIN; PEGYLATED INTERFERON;
ANTIVIRAL THERAPY; TELAPREVIR; COMBINATION; PREVALENCE; BOCEPREVIR;
PLACEBO
AB IMPORTANCE The efficacy of directly acting antiviral agents in interferon-free regimens for the treatment of chronic hepatitis C infections needs to be evaluated in different populations.
OBJECTIVE To determine the efficacy and safety of sofosbuvir with weight-based or low-dose ribavirin among a population with unfavorable treatment characteristics.
DESIGN, SETTING, AND PATIENTS Single-center, randomized, 2-part, open-label phase 2 study involving 60 treatment-naive patients with hepatitis C virus (HCV) genotype 1 enrolled at the National Institutes of Health (October 2011-April 2012).
INTERVENTIONS In the study's first part, 10 participants with early to moderate liver fibrosis were treated with 400 mg/d of sofosbuvir and weight-based ribavirin for 24 weeks. In the second part, 50 participants with all stages of liver fibrosis were randomized 1: 1 to receive 400 mg of sofosbuvir with either weight-based or low-dose 600 mg/d of ribavirin for 24 weeks.
MAIN OUTCOMES AND MEASURES The primary study end point was the proportion of participants with undetectable HCV viral load 24 weeks after treatment completion (sustained virologic response of 24 weeks [SVR24]).
RESULTS In the first part of the study, 9 participants (90%; 95% CI, 55%-100%) achieved SVR24. In the second part, 7 participants (28%) in the weight-based group and 10 (40%) in the low-dose group relapsed after treatment completion leading to SVR24 rates of 68%(95% CI, 46%-85%) in the weight-based group and 48%(95% CI, 28%-69%; P = .20) in the low-dose group. Twenty individuals participated in a pharmacokinetic-viral kinetic substudy, which demonstrated a slower loss rate of infectious virus in relapsers than in participants who achieved SVR (clearance, 3.57/d vs 5.60/d; P = .009). The most frequent adverse events were headache, anemia, fatigue, and nausea. There were 7 grade 3 events including anemia, neutropenia, nausea, hypophosphatemia, and cholelithiasis or pancreatitis. No one discontinued treatment due to adverse events.
CONCLUSION AND RELEVANCE In a population of patients with a high prevalence of unfavorable traditional predictors of treatment response, a 24-week regimen of sofosbuvir and weight-based or low-dose ribavirin resulted in SVR24 rates of 68% and 48%, respectively.
C1 [Osinusi, Anuoluwapo; Meissner, Eric G.; Lee, Yu-Jin; Nelson, Amy; Sneller, Michael; Kohli, Anita; Barrett, Lisa; Shivakumar, Bhavana; Wroblewski, Susan; Zhang, Xiao; Polis, Michael A.; Fauci, Anthony S.; Kottilil, Shyamasundaran] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Osinusi, Anuoluwapo; Silk, Rachel; Kotb, Colleen] Sci Applicat Int Corp SAIC Frederick Inc, Clin Res Directorate, Clin Monitoring Res Program, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Bon, Dimitra; Herrmann, Eva] Goethe Univ Frankfurt, Inst Biostat & Math Modeling, D-60054 Frankfurt, Germany.
[Heytens, Laura; Kwan, Richard; Masur, Henry] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
[Proschan, Michael] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
[Gu, Wenjuan; Dewar, Robin; Highbarger, Helene] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Teferi, Geb; Chavez, Jose] Unity Hlth Care Inc, Washington, DC USA.
[Talwani, Rohit] Univ Maryland, Dept Infect Dis, Baltimore, MD 21201 USA.
[Fishbein, Dawn] MedStar Washington Hosp Ctr, Dept Infect Dis, Washington, DC USA.
[Kleiner, David] NCI, Dept Pathol, Bethesda, MD 20892 USA.
[Wood, Brad J.] NIH, Ctr Intervent Oncol Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
[Wood, Brad J.] NCI, Bethesda, MD 20892 USA.
[Symonds, William T.; Subramanian, Mani; McHutchison, John] Gilead Sci Inc, Foster City, CA 94404 USA.
RP Kottilil, S (reprint author), NIAID, Immunopathogenesis Sect, Immunoregulat Lab, NIH, Bldg 10,Room 11N204, Bethesda, MD 20892 USA.
EM skottilil@niaid.nih.gov
OI Polis, Michael/0000-0002-9151-2268; Kleiner, David/0000-0003-3442-4453
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; National Institute of Allergy and Infectious
Diseases; German Research Foundation by the clinical research unit KFO
129
FX This project was funded in whole by grant HHSN261200800001E from the
National Cancer Institute, National Institutes of Health. This research
was supported in part by the National Institute of Allergy and
Infectious Diseases and by the German Research Foundation by the
clinical research unit KFO 129. Pharmasset Pharmaceuticals and
subsequently Gilead Sciences provided sofosbuvir and scientific advice.
NR 23
TC 173
Z9 177
U1 1
U2 17
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD AUG 28
PY 2013
VL 310
IS 8
BP 804
EP 811
DI 10.1001/jama.2013.109309
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 206YA
UT WOS:000323561400020
PM 23982366
ER
PT J
AU Ma, SS
AF Ma, Steven S.
TI Reductions in Funding for Medical Research
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Letter
ID BIOMEDICAL-RESEARCH
C1 NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA.
RP Ma, SS (reprint author), NIH, Vaccine Res Ctr, 40 Convent Dr,Room 3613, Bethesda, MD 20892 USA.
EM steven@stevensma.com
NR 4
TC 0
Z9 0
U1 0
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD AUG 28
PY 2013
VL 310
IS 8
BP 854
EP 855
DI 10.1001/jama.2013.170804
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 206YA
UT WOS:000323561400030
PM 23982376
ER
PT J
AU Berezhkovskii, AM
Skvortsov, AT
AF Berezhkovskii, Alexander M.
Skvortsov, Alexei T.
TI Aris-Taylor dispersion with drift and diffusion of particles on the tube
wall
SO JOURNAL OF CHEMICAL PHYSICS
LA English
DT Article
ID FLOWS; CHANNELS; MODELS
AB A laminar stationary flow of viscous fluid in a cylindrical tube enhances the rate of diffusion of Brownian particles along the tube axis. This so-called Aris-Taylor dispersion is due to the fact that cumulative times, spent by a diffusing particle in layers of the fluid moving with different velocities, are random variables which depend on the realization of the particle stochastic trajectory in the radial direction. Conceptually similar increase of the diffusivity occurs when the particle randomly jumps between two states with different drift velocities. Here we develop a theory that contains both phenomena as special limiting cases. It is assumed (i) that the particle in the flow can reversibly bind to the tube wall, where it moves with a given drift velocity and diffusivity, and (ii) that the radial and longitudinal diffusivities of the particle in the flow may be different. We derive analytical expressions for the effective drift velocity and diffusivity of the particle, which show how these quantities depend on the geometric and kinetic parameters of the model.
C1 [Berezhkovskii, Alexander M.] NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
[Skvortsov, Alexei T.] Def Sci & Technol Org, Land Div, Fishermans Bend, Vic 3207, Australia.
RP Skvortsov, AT (reprint author), Def Sci & Technol Org, Land Div, Fishermans Bend, Vic 3207, Australia.
EM alex.skvortsov@dsto.defence.gov
FU Intramural Research Program of the National of Institutes of Health
(NIH), Center for Information Technology
FX This study was supported by the Intramural Research Program of the
National of Institutes of Health (NIH), Center for Information
Technology. We are grateful to Vemuri Balakotaiah and Chiu-On Ng for
helpful discussions. We thank Chris Woodruff for his careful reading of
the paper and useful comments.
NR 35
TC 9
Z9 9
U1 2
U2 13
PU AMER INST PHYSICS
PI MELVILLE
PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1,
MELVILLE, NY 11747-4501 USA
SN 0021-9606
J9 J CHEM PHYS
JI J. Chem. Phys.
PD AUG 28
PY 2013
VL 139
IS 8
AR 084101
DI 10.1063/1.4818733
PG 7
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 211RO
UT WOS:000323928000004
PM 24006968
ER
PT J
AU Coulibaly, YI
Dembele, B
Diallo, AA
Kristensen, S
Konate, S
Dolo, H
Dicko, I
Sangare, MB
Keita, F
Boatin, BA
Traore, AK
Nutman, TB
Klion, AD
Toure, YT
Traore, SF
AF Coulibaly, Yaya Ibrahim
Dembele, Benoit
Diallo, Abdallah Amadou
Kristensen, Sibylle
Konate, Siaka
Dolo, Housseini
Dicko, Ilo
Sangare, Moussa Brema
Keita, Falaye
Boatin, Boakye A.
Traore, Abdel Kader
Nutman, Thomas B.
Klion, Amy D.
Toure, Yeya Tiemoko
Traore, Sekou Fantamady
TI Wuchereria bancrofti transmission pattern in southern Mali prior to and
following the institution of mass drug administration
SO PARASITES & VECTORS
LA English
DT Article
ID LYMPHATIC FILARIASIS; ANOPHELES-GAMBIAE; MOSQUITOS; ELIMINATION;
IVERMECTIN; INTENSITY; DYNAMICS; VECTORS; GHANA
AB Background: The Global Programme to Eliminate Lymphatic Filariasis (GPELF) was launched in 2000 with the goal of stopping transmission of lymphatic filariasis (LF) through yearly mass drug administration (MDA). Although preliminary surveys of the human population in Mali suggested that Wuchereria bancrofti infection was highly endemic in the Sikasso district, baseline entomological data were required to confirm high levels of transmission prior to the selection of villages in this region for a study of the impact of MDA on transmission of LF by anopheline vectors.
Methods: W. bancrofti transmission was assessed in 2001 (pre-MDA) and 2002 (post-MDA) in the Central District of Sikasso in southern Mali by dissection of Anopheles mosquitoes caught using the human landing catch (HLC) method. The relative frequencies and molecular forms of An. gambiae complex were determined.
Results: The majority (86%) of the anopheline vectors captured were identified as An. gambiae complex, and these accounted for >90% of the entomological inoculation rate (EIR) during both years of the study. There was a dramatic decrease in the number of An. gambiae complex mosquitoes captured and in the An. gambiae complex infectivity rates following MDA, accounting for the observed decrease in EIR in 2002 (from 12.55 to 3.79 infective bites per person during the transmission season). An. funestus complex mosquitoes were responsible for a low level of transmission, which was similar during both years of the study (1.2 infective bites per person during the transmission season in 2001 and 1.03 in 2002).
Conclusions: Based on the entomological data from this study, the district of Sikasso was confirmed as an area of high W. bancrofti transmission. This led to the selection of this area for a multi-national study on the effects of MDA on LF transmission by anopheline vectors. Comparison of vector transmission parameters prior to and immediately following the first round of MDA demonstrated a significant decrease in overall transmission. Importantly, the dramatic variability in EIR over the transmission season suggests that the efficacy of MDA can be maximized by delivering drug at the beginning of the rainy season (just prior to the peak of transmission).
C1 [Coulibaly, Yaya Ibrahim; Dembele, Benoit; Diallo, Abdallah Amadou; Konate, Siaka; Dolo, Housseini; Dicko, Ilo; Sangare, Moussa Brema; Keita, Falaye; Toure, Yeya Tiemoko; Traore, Sekou Fantamady] Univ Sci Tech & Technol Bamako USTTB, Mali Int Ctr Excellence Res ICER, Bamako, Mali.
[Kristensen, Sibylle] Univ Alabama Birmingham, Dept Epidemiol & Int Hlth, Birmingham, AL USA.
[Coulibaly, Yaya Ibrahim; Traore, Abdel Kader] CNAM, Bamako, Mali.
[Boatin, Boakye A.] World Hlth Org, Geneva, Switzerland.
[Nutman, Thomas B.; Klion, Amy D.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Coulibaly, YI (reprint author), Univ Sci Tech & Technol Bamako USTTB, Mali Int Ctr Excellence Res ICER, Bamako, Mali.
EM yicoulibaly@icermali.org
OI Klion, Amy/0000-0002-4986-5326
FU Special Program for Research and Training in Tropical Diseases
(WHO/UNDP/World Bank) [A00583]; Division of Intramural Research, NIAID,
NIH
FX We would like to address special thanks to the local health care staff
of Sikasso and Kolokoba, to the villagers and all the volunteers for
their cooperation and participation to the field activities. The Special
Program for Research and Training in Tropical Diseases (WHO/UNDP/World
Bank) Grant ID A00583 and the Division of Intramural Research, NIAID,
NIH funded this study.
NR 21
TC 8
Z9 8
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1756-3305
J9 PARASITE VECTOR
JI Parasites Vectors
PD AUG 28
PY 2013
VL 6
AR 247
DI 10.1186/1756-3305-6-247
PG 7
WC Parasitology
SC Parasitology
GA 209UU
UT WOS:000323786500001
PM 23981378
ER
PT J
AU Chen, J
Qian, HH
Horai, R
Chan, CC
Falick, Y
Caspi, RR
AF Chen, Jun
Qian, Haohua
Horai, Reiko
Chan, Chi-Chao
Falick, Yishay
Caspi, Rachel R.
TI Comparative Analysis of Induced vs. Spontaneous Models of Autoimmune
Uveitis Targeting the Interphotoreceptor Retinoid Binding Protein
SO PLOS ONE
LA English
DT Article
ID ENDOTOXIN-INDUCED UVEITIS; UVEORETINITIS EAU; LIPOTEICHOIC ACID;
DISEASE; MICE; RAT; MECHANISMS; IRBP; TH1; SUSCEPTIBILITY
AB Animal models of autoimmunity to the retina mimic specific features of human uveitis, but no model by itself reproduces the full spectrum of human disease. We compared three mouse models of uveitis that target the interphotoreceptor retinoid binding protein (IRBP): (i) the "classical" model of experimental autoimmune uveitis (EAU) induced by immunization with IRBP; (ii) spontaneous uveitis in IRBP T cell receptor transgenic mice (R161H) and (iii) spontaneous uveitis in Autoimmune Regulator (AIRE)(-/-) mice. Disease course and severity, pathology and changes in visual function were studied using fundus imaging and histological examinations, optical coherence tomography and electroretinography. All models were on the B10.RIII background. Unlike previously reported, IRBP-induced EAU in B10.RIII mice exhibited two distinct patterns of disease depending on clinical scores developed after onset: severe monophasic with extensive destruction of the retina and rapid loss of visual signal, or lower grade with a prolonged chronic phase culminating after several months in retinal degeneration and loss of vision. R161H and AIRE(-/-) mice spontaneously developed chronic progressive inflammation; visual function declined gradually as retinal degeneration developed. Spontaneous uveitis in R161H mice was characterized by persistent cellular infiltrates and lymphoid aggregation, whereas AIRE(-/-) mice characteristically developed multi-focal infiltrates and severe choroidal inflammation. These data demonstrate variability and unique distinguishing features in the different models of uveitis, suggesting that each one can represent distinct aspects of uveitis in humans.
C1 [Chen, Jun; Horai, Reiko; Falick, Yishay; Caspi, Rachel R.] NEI, Immunoregulat Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Qian, Haohua] NEI, Visual Funct Core, NIH, Bethesda, MD 20892 USA.
[Chan, Chi-Chao] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Chen, J (reprint author), Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510275, Guangdong, Peoples R China.
EM chenju@nei.nih.gov; caspir@nei.nih.gov
OI Caspi, Rachel/0000-0002-7140-7671
FU National Institutes of Health (NIH)/National Eye Institute (NEI)
[EY000184]
FX The study was supported by National Institutes of Health (NIH)/National
Eye Institute (NEI) Intramural funding, project #EY000184. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 37
TC 9
Z9 9
U1 0
U2 9
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 28
PY 2013
VL 8
IS 8
AR e72161
DI 10.1371/journal.pone.0072161
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 209DG
UT WOS:000323733800034
PM 24015215
ER
PT J
AU Hu, Y
Bai, L
Geiger, T
Goldberger, N
Walker, RC
Green, JE
Wakefield, LM
Hunter, KW
AF Hu, Ying
Bai, Ling
Geiger, Thomas
Goldberger, Natalie
Walker, Renard C.
Green, Jeffery E.
Wakefield, Lalage M.
Hunter, Kent W.
TI Genetic Background May Contribute to PAM50 Gene Expression Breast Cancer
Subtype Assignments
SO PLOS ONE
LA English
DT Article
ID INDUCED MAMMARY-TUMOR; TRANSCRIPTIONAL NETWORK; MOLECULAR PORTRAITS;
CELL-LINES; MOUSE; METASTASIS; SUSCEPTIBILITY; PROGRESSION; POPULATION;
PREDICTOR
AB Recent advances in genome wide transcriptional analysis have provided greater insights into the etiology and heterogeneity of breast cancer. Molecular signatures have been developed that stratify the conventional estrogen receptor positive or negative categories into subtypes that are associated with differing clinical outcomes. It is thought that the expression patterns of the molecular subtypes primarily reflect cell-of-origin or tumor driver mutations. In this study however, using a genetically engineered mouse mammary tumor model we demonstrate that the PAM50 subtype signature of tumors driven by a common oncogenic event can be significantly influenced by the genetic background on which the tumor arises. These results have important implications for interpretation of "snapshot" expression profiles, as well as suggesting that incorporation of genetic background effects may allow investigation into phenotypes not initially anticipated in individual mouse models of cancer.
C1 [Hu, Ying] Ctr Biomed Informat & Informat Technol, Bethesda, MD USA.
[Bai, Ling; Geiger, Thomas; Goldberger, Natalie; Walker, Renard C.; Green, Jeffery E.; Wakefield, Lalage M.; Hunter, Kent W.] NCI, Lab Canc Biol & Genet, CCR, NIH, Bethesda, MD 20892 USA.
RP Hunter, KW (reprint author), NCI, Lab Canc Biol & Genet, CCR, NIH, Bethesda, MD 20892 USA.
EM hunterk@mail.nih.gov
FU National Institutes of Health, NCI, Center for Cancer Research
FX This work was supported by the National Institutes of Health, NCI,
Center for Cancer Research, Intramural Research Program. The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 29
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 AUG 28
PY 2013
VL 8
IS 8
AR e72287
DI 10.1371/journal.pone.0072287
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 209DG
UT WOS:000323733800044
ER
PT J
AU Kim, SH
Wanasen, N
Paldurai, A
Xiao, S
Collins, PL
Samal, SK
AF Kim, Shin-Hee
Wanasen, Nanchaya
Paldurai, Anandan
Xiao, Sa
Collins, Peter L.
Samal, Siba K.
TI Newcastle Disease Virus Fusion Protein Is the Major Contributor to
Protective Immunity of Genotype-Matched Vaccine
SO PLOS ONE
LA English
DT Article
ID RECOMBINANT VIRUSES; FOREIGN GENE; CHICKEN; STRAIN; EXPRESSION;
OUTBREAKS; EFFICACY; HN; PATHOGENICITY; REPLICATION
AB Virulent strains of Newcastle disease virus (NDV) can cause devastating disease in chickens worldwide. Although the current vaccines are substantially effective, they do not completely prevent infection, virus shedding and disease. To produce genotype-matched vaccines, a full-genome reverse genetics system has been used to generate a recombinant virus in which the F protein cleavage site has been changed to that of avirulent vaccine virus. In the other strategy, the vaccines have been generated by replacing the F and HN genes of a commercial vaccine strain with those from a genotype-matched virus. However, the protective efficacy of a chimeric virus vaccine has not been directly compared with that of a full-genome virus vaccine developed by reverse genetics. Therefore, in this study, we evaluated the protective efficacy of genotype VII matched chimeric vaccines by generating three recombinant viruses based on avirulent LaSota (genotype II) strain in which the open reading frames (ORFs) encoding the F and HN proteins were replaced, individually or together, with those of the circulating and highly virulent Indonesian NDV strain Ban/010. The cleavage site of the Ban/010 F protein was mutated to the avirulent motif found in strain LaSota. In vitro growth characteristics and a pathogenicity test indicated that all three chimeric viruses retained the highly attenuated phenotype of the parental viruses. Immunization of chickens with chimeric and full-length genome VII vaccines followed by challenge with virulent Ban/010 or Texas GB (genotype II) virus demonstrated protection against clinical disease and death. However, only those chickens immunized with chimeric rLaSota expressing the F or F plus HN proteins of the Indonesian strain were efficiently protected against shedding of Ban/010 virus. Our findings showed that genotype-matched vaccines can provide protection to chickens by efficiently preventing spread of virus, primarily due to the F protein.
C1 [Kim, Shin-Hee; Wanasen, Nanchaya; Paldurai, Anandan; Xiao, Sa; Samal, Siba K.] Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA.
[Collins, Peter L.] NIAID, Infect Dis Lab, Bethesda, MD 20892 USA.
RP Samal, SK (reprint author), Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA.
EM ssamal@umd.edu
FU NIAID [N01A060009]; NIAID, NIH
FX This research was supported by NIAID contract N01A060009 (85% support)
and the NIAID, NIH, Intramural Research Program (15% support). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 35
TC 12
Z9 12
U1 0
U2 11
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 28
PY 2013
VL 8
IS 8
AR e74022
DI 10.1371/journal.pone.0074022
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 209DG
UT WOS:000323733800108
PM 24015313
ER
PT J
AU Leysath, CE
Phillips, DD
Crown, D
Fattah, RJ
Moayeri, M
Leppla, SH
AF Leysath, Clinton E.
Phillips, Damilola D.
Crown, Devorah
Fattah, Rasem J.
Moayeri, Mahtab
Leppla, Stephen H.
TI Anthrax Edema Factor Toxicity Is Strongly Mediated by the N-end Rule
SO PLOS ONE
LA English
DT Article
ID BACILLUS-ANTHRACIS; LETHAL FACTOR; TOXIN; BINDING; PROTEIN; MACROPHAGES;
PEPTIDASE; PROLINE; PATHWAY; CYCLASE
AB Anthrax edema factor (EF) is a calmodulin-dependent adenylate cyclase that converts adenosine triphosphate (ATP) into 3'-5'-cyclic adenosine monophosphate (cAMP), contributing to the establishment of Bacillus anthracis infections and the resulting pathophysiology. We show that EF adenylate cyclase toxin activity is strongly mediated by the N-end rule, and thus is dependent on the identity of the N-terminal amino acid. EF variants having different N-terminal residues varied by more than 100-fold in potency in cultured cells and mice. EF variants having unfavorable, destabilizing N-terminal residues showed much greater activity in cells when the E1 ubiquitin ligase was inactivated or when proteasome inhibitors were present. Taken together, these results show that EF is uniquely affected by ubiquitination and/or proteasomal degradation.
C1 [Leysath, Clinton E.; Phillips, Damilola D.; Crown, Devorah; Fattah, Rasem J.; Moayeri, Mahtab; Leppla, Stephen H.] Natl Inst Allergy & Infect Dis, NIH, Parasit Dis Lab, Bethesda, MD USA.
RP Leppla, SH (reprint author), Natl Inst Allergy & Infect Dis, NIH, Parasit Dis Lab, Bethesda, MD USA.
EM sleppla@niaid.nih.gov
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases
FX This research 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 27
TC 2
Z9 2
U1 2
U2 14
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 28
PY 2013
VL 8
IS 8
AR UNSP e74474
DI 10.1371/journal.pone.0074474
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 209DG
UT WOS:000323733800114
PM 24015319
ER
PT J
AU Horinouchi, Y
Summers, FA
Ehrenshaft, M
Houchi, H
Tamaki, T
Minakuchi, K
Mason, RP
AF Horinouchi, Yuya
Summers, Fiona A.
Ehrenshaft, Marilyn
Houchi, Hitoshi
Tamaki, Toshiaki
Minakuchi, Kazuo
Mason, Ronald P.
TI Cytotoxicity evaluation of environmental chemicals via free radical
detection using newly technique immuno-spin trapping, In-Cell Western
and confocal microscopy
SO TOXICOLOGY LETTERS
LA English
DT Meeting Abstract
CT 49th Congress of the European-Societies-of-Toxicology (EUROTOX)
CY SEP 01-04, 2013
CL Interlaken, SWITZERLAND
SP European Soc Toxicol (EUROTOX), ECETOC, Roche, Syngenta, AstraZeneca, Sanofi, Basilea Pharmaceutica, ACEA Biosciences Inc, European Crop Protect, Bioservice Sci Labs GmbH, Oekotoxzentrum Ctr Ecotox, Swiss Confederat, Fed Dept Home Affairs, Fed Off Publ Hlth (FOPH), BASF, SCAHT, Johnson & Johnson, Janssen Pharmaceut Co, Natl Ctr Replacement, Refinement & Reduct Anim Res, ILSI, SERVIER, RCC, Nestle, Suva Pro, Interpharma, Covance, Novartis, Merck, BioReliance
C1 [Horinouchi, Yuya; Minakuchi, Kazuo] Tokushima Univ Hosp, Dept Pharm, Tokushima, Japan.
[Horinouchi, Yuya; Tamaki, Toshiaki] Univ Tokushima, Dept Pharmacol, Inst Hlth Biosci, Grad Sch, Tokushima 770, Japan.
[Summers, Fiona A.; Ehrenshaft, Marilyn; Mason, Ronald P.] NIEHS, Free Rad Metab Grp, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
[Houchi, Hitoshi] Kagawa Univ Hosp, Dept Pharm, Takamatsu, Kagawa, Japan.
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 0378-4274
J9 TOXICOL LETT
JI Toxicol. Lett.
PD AUG 28
PY 2013
VL 221
SU S
BP S102
EP S102
DI 10.1016/j.toxlet.2013.05.152
PG 1
WC Toxicology
SC Toxicology
GA 210WO
UT WOS:000323865800309
ER
PT J
AU Thompson, KL
Chen, T
Couttet, P
Ellinger-Ziegelbauer, H
Kanki, M
Kelsall, J
Boitier, E
Nassirpour, R
Searfoss, G
Sharapova, T
de la Moureyre-Spire, C
Yuen, P
O'Lone, R
AF Thompson, K. L.
Chen, T.
Couttet, P.
Ellinger-Ziegelbauer, H.
Kanki, M.
Kelsall, J.
Boitier, E.
Nassirpour, R.
Searfoss, G.
Sharapova, T.
de la Moureyre-Spire, C.
Yuen, P.
O'Lone, R.
TI Multi-laboratory assessment of best practices for quantification of
microRNAs associated with isoproterenol-induced myocardial injury in the
urine and plasma of rats
SO TOXICOLOGY LETTERS
LA English
DT Meeting Abstract
CT 49th Congress of the European-Societies-of-Toxicology (EUROTOX)
CY SEP 01-04, 2013
CL Interlaken, SWITZERLAND
SP European Soc Toxicol (EUROTOX), ECETOC, Roche, Syngenta, AstraZeneca, Sanofi, Basilea Pharmaceutica, ACEA Biosciences Inc, European Crop Protect, Bioservice Sci Labs GmbH, Oekotoxzentrum Ctr Ecotox, Swiss Confederat, Fed Dept Home Affairs, Fed Off Publ Hlth (FOPH), BASF, SCAHT, Johnson & Johnson, Janssen Pharmaceut Co, Natl Ctr Replacement, Refinement & Reduct Anim Res, ILSI, SERVIER, RCC, Nestle, Suva Pro, Interpharma, Covance, Novartis, Merck, BioReliance
C1 [Thompson, K. L.] CDER, Silver Spring, MD USA.
[Chen, T.] NCTR, Jefferson, AR USA.
[Couttet, P.] Novartis Pharma AG, Basel, Switzerland.
[Ellinger-Ziegelbauer, H.] Bayer Pharma AG, Wuppertal, Germany.
[Kanki, M.] Astellas Pharrna Inc, Osaka, Japan.
[Kelsall, J.] AstraZeneca, Macclesfield, Cheshire, England.
[Boitier, E.] Sanofi, Vitry Sur Seine, France.
[Nassirpour, R.] Pfizer, Andover, MA USA.
[Searfoss, G.] Lilly, Indianapolis, IN USA.
[Sharapova, T.] Abbott Labs, Abbott Pk, IL 60064 USA.
[de la Moureyre-Spire, C.] Servier, Gidy, France.
[Yuen, P.] NIDDK, NIH, Bethesda, MD USA.
[O'Lone, R.] ILSI Hlth & Environm Sci Inst, Washington, DC USA.
RI Yuen, Peter/B-1954-2008
OI Yuen, Peter/0000-0001-9557-3909
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 0378-4274
J9 TOXICOL LETT
JI Toxicol. Lett.
PD AUG 28
PY 2013
VL 221
SU S
BP S66
EP S66
DI 10.1016/j.toxlet.2013.05.037
PG 1
WC Toxicology
SC Toxicology
GA 210WO
UT WOS:000323865800199
ER
PT J
AU Thompson, KL
Chen, T
Couttet, P
Ellinger-Ziegelbauer, H
Kanki, M
Kelsall, J
Boitier, E
Nassirpour, R
Searfoss, G
Sharapova, T
de la Moureyre-Spire, C
Yuen, P
O'Lone, R
AF Thompson, K. L.
Chen, T.
Couttet, P.
Ellinger-Ziegelbauer, H.
Kanki, M.
Kelsall, J.
Boitier, E.
Nassirpour, R.
Searfoss, G.
Sharapova, T.
de la Moureyre-Spire, Catherine
Yuen, P.
O'Lone, R.
TI The HESI inter-laboratory miRNA project
SO TOXICOLOGY LETTERS
LA English
DT Meeting Abstract
CT 49th Congress of the European-Societies-of-Toxicology (EUROTOX)
CY SEP 01-04, 2013
CL Interlaken, SWITZERLAND
SP European Soc Toxicol (EUROTOX), ECETOC, Roche, Syngenta, AstraZeneca, Sanofi, Basilea Pharmaceutica, ACEA Biosciences Inc, European Crop Protect, Bioservice Sci Labs GmbH, Oekotoxzentrum Ctr Ecotox, Swiss Confederat, Fed Dept Home Affairs, Fed Off Publ Hlth (FOPH), BASF, SCAHT, Johnson & Johnson, Janssen Pharmaceut Co, Natl Ctr Replacement, Refinement & Reduct Anim Res, ILSI, SERVIER, RCC, Nestle, Suva Pro, Interpharma, Covance, Novartis, Merck, BioReliance
C1 [Thompson, K. L.] CDER, Silver Spring, MD USA.
[Chen, T.] NCTR, Jefferson, AR USA.
[Couttet, P.] Novartis Pharma AG, Basel, Switzerland.
[Ellinger-Ziegelbauer, H.] Bayer Pharma AG, Wuppertal, Germany.
[Kanki, M.] Astellas Pharma Inc, Osaka, Japan.
[Kelsall, J.] AstraZeneca, Macclesfield, Cheshire, England.
[Boitier, E.] Sanofi, Vitry Sur Seine, France.
[Nassirpour, R.] Pfizer, Andover, MA USA.
[Searfoss, G.] Lilly, Indianapolis, IN USA.
[Sharapova, T.] Abbott Labs, Abbott Pk, IL 60064 USA.
[de la Moureyre-Spire, Catherine] Servier, Gidy, France.
[Yuen, P.] NIDDK, NIH, Bethesda, MD USA.
[O'Lone, R.] ILSI Hlth & Environm Sci Inst, Washington, DC USA.
RI Yuen, Peter/B-1954-2008
OI Yuen, Peter/0000-0001-9557-3909
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 0378-4274
J9 TOXICOL LETT
JI Toxicol. Lett.
PD AUG 28
PY 2013
VL 221
SU S
BP S48
EP S48
DI 10.1016/j.toxlet.2013.06.176
PG 1
WC Toxicology
SC Toxicology
GA 210WO
UT WOS:000323865800149
ER
PT J
AU Cho, YT
Ernst, M
Fudge, JL
AF Cho, Youngsun T.
Ernst, Monique
Fudge, Julie L.
TI Cortico-Amygdala-Striatal Circuits Are Organized as Hierarchical
Subsystems through the Primate Amygdala
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID MEDIAL PREFRONTAL CORTEX; HUMAN ORBITOFRONTAL CORTEX; CAUDAL VENTRAL
STRIATUM; SURFACE-BASED ATLASES; HUMAN CEREBRAL-CORTEX; RHESUS-MONKEY;
MACAQUE MONKEY; NUCLEUS-ACCUMBENS; BASOLATERAL AMYGDALA; CORTICOSTRIATAL
CONNECTIONS
AB The prefrontal and insula cortex, amygdala, and striatum are key regions for emotional processing, yet the amygdala's role as an interface between the cortex and striatum is not well understood. In the nonhuman primate ( Macaque fascicularis), we analyzed a collection of bidirectional tracer injections in the amygdala to understand how cortical inputs and striatal outputs are organized to form integrated cortico-amygdala-striatal circuits. Overall, diverse prefrontal and insular cortical regions projected to the basal and accessory basal nuclei of the amygdala. In turn, these amygdala regions projected to widespread striatal domains extending well beyond the classic ventral striatum. Analysis of the cases in aggregate revealed a topographic colocalization of cortical inputs and striatal outputs in the amygdala that was additionally distinguished by cortical cytoarchitecture. Specifically, the degree of cortical laminar differentiation of the cortical inputs predicted amygdalostriatal targets, and distinguished three main cortico-amygdala-striatal circuits. These three circuits were categorized as "primitive," "intermediate," and "developed," respectively, to emphasize the relative phylogenetic and ontogenetic features of the cortical inputs. Within the amygdala, these circuits appeared arranged in a pyramidal-like fashion, with the primitive circuit found in all examined subregions, and subsequent circuits hierarchically layered in discrete amygdala subregions. This arrangement suggests a stepwise integration of the functions of these circuits across amygdala subregions, providing a potential mechanism through which internal emotional states are managed with external social and sensory information toward emotionally informed complex behaviors.
C1 [Cho, Youngsun T.; Fudge, Julie L.] Univ Rochester, Med Ctr, Dept Neurobiol & Anat, Rochester, NY 14642 USA.
[Fudge, Julie L.] Univ Rochester, Med Ctr, Dept Psychiat, Rochester, NY 14642 USA.
[Ernst, Monique] NIMH, NIH, Emot Dev & Affect Neurosci Branch, Bethesda, MD 20892 USA.
RP Fudge, JL (reprint author), Univ Rochester, Med Ctr, Dept Neurobiol & Anat, 601 Elmwood Ave, Rochester, NY 14642 USA.
EM julie_fudge@urmc.rochester.edu
FU National Institutes of Mental Health [F30 MH09126, R01MH63291]; Clinical
and Translational Sciences Institute [TL1RR024135]
FX This work was funded through support of the National Institutes of
Mental Health F30 MH09126 (Y.T.C.) and R01MH63291 (J.L.F.), and the
Clinical and Translational Sciences Institute TL1RR024135 (Y.T.C.). We
thank Owen Zacharias for his photography and Daniel Tylee for assistance
with histology and immunocytochemistry. We also acknowledge helpful
criticisms and comments on a draft of this manuscript from Dr. Lizabeth
Romanski.
NR 121
TC 19
Z9 19
U1 3
U2 17
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 AUG 28
PY 2013
VL 33
IS 35
BP 14017
EP 14030
DI 10.1523/JNEUROSCI.0170-13.2013
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA 209AZ
UT WOS:000323727000010
PM 23986238
ER
PT J
AU Sabino, EC
Ribeiro, AL
Salemi, VMC
Ianni, BM
Nastari, L
Fernandes, F
Oliveira, CD
Antunes, AP
Menezes, MM
Patavino, GM
Capuani, L
de Almeida-Neto, C
Sachdev, V
Carrick, DM
Wright, D
Kavounis, K
Gonzalez, TT
Custer, B
Busch, MP
Murphy, EL
Carneiro-Proietti, AB
AF Sabino, Ester C.
Ribeiro, Antonio L.
Salemi, Vera M. C.
Ianni, Barbara M.
Nastari, Luciano
Fernandes, Fabio
Oliveira, Claudia Di Lorenzo
Antunes, Andre P.
Menezes, Marcia M.
Patavino, Giuseppina M.
Capuani, Ligia
de Almeida-Neto, Cesar
Sachdev, Vandana
Carrick, Danielle M.
Wright, David
Kavounis, Katherine
Gonzalez, Thelma T.
Custer, Brian
Busch, Michael P.
Murphy, Edward L.
Carneiro-Proietti, Anna-Barbara
TI Response to Letters Regarding Article, "Ten-Year Incidence of Chagas
Cardiomyopathy Among Asymptomatic, Trypanosoma cruzi-Seropositive Former
Blood Donors"
SO CIRCULATION
LA English
DT Letter
ID ELECTROCARDIOGRAPHIC ABNORMALITIES; DISEASE; PREDICTORS
C1 [Sabino, Ester C.] Univ Sao Paulo, Dept Infect Dis, Sao Paulo, Brazil.
[Sabino, Ester C.] Univ Sao Paulo, Inst Trop Med, Sao Paulo, Brazil.
[Ribeiro, Antonio L.] Univ Fed Minas Gerais, Hosp Clin, Belo Horizonte, MG, Brazil.
[Ribeiro, Antonio L.] Univ Fed Minas Gerais, Fac Med, Belo Horizonte, MG, Brazil.
[Salemi, Vera M. C.; Ianni, Barbara M.; Nastari, Luciano; Fernandes, Fabio] Univ Sao Paulo, Fac Med, Heart Inst InCor, Cardiomyopathy Unit, Sao Paulo, Brazil.
[Oliveira, Claudia Di Lorenzo] Univ Fed Sao Joao del Rei, Divinopolis, Brazil.
[Antunes, Andre P.; Menezes, Marcia M.] Prontosocor Montes Claros, Ctr Ciencias Biol & Saude, Montes Claros, MG, Brazil.
[Patavino, Giuseppina M.; Capuani, Ligia; de Almeida-Neto, Cesar] Fundacao Prosangue Hemoctr Sao Paulo, Sao Paulo, Brazil.
[Sachdev, Vandana] NHLBI, Bethesda, MD 20892 USA.
[Carrick, Danielle M.; Wright, David; Kavounis, Katherine] Westat Corp, Rockville, MD USA.
[Gonzalez, Thelma T.; Custer, Brian; Busch, Michael P.] Blood Syst Res Inst, San Francisco, CA USA.
[Murphy, Edward L.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Carneiro-Proietti, Anna-Barbara] Hemominas, Belo Horizonte, MG, Brazil.
RP Sabino, EC (reprint author), Univ Sao Paulo, Dept Infect Dis, Sao Paulo, Brazil.
RI Ribeiro, Antonio/C-2707-2009; Nastari, Luciano/C-8528-2012; de
Almeida-Neto, Cesar/O-9224-2014; Fernandes, Fabio/D-5994-2012; Sabino,
Ester/F-7750-2010; Salemi, Vera/C-9104-2013; Ianni, Barbara/C-7689-2012
OI Capuani, Ligia/0000-0002-3467-6805; Ribeiro,
Antonio/0000-0002-2740-0042; Nastari, Luciano/0000-0002-7959-3827;
Sabino, Ester/0000-0003-2623-5126; Salemi, Vera/0000-0002-7152-1810;
Ianni, Barbara/0000-0002-1588-5492
NR 5
TC 0
Z9 0
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD AUG 27
PY 2013
VL 128
IS 9
BP E137
EP E138
DI 10.1161/CIRCULATIONAHA.113.004018
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 208BF
UT WOS:000323649600006
PM 23979636
ER
PT J
AU Tanoue, K
Jenkins, LMM
Durell, SR
Debnath, S
Sakai, H
Tagad, HD
Ishida, K
Appella, E
Mazur, SJ
AF Tanoue, Kan
Jenkins, Lisa M. Miller
Durell, Stewart R.
Debnath, Subrata
Sakai, Hiroyasu
Tagad, Harichandra D.
Ishida, Kazushige
Appella, Ettore
Mazur, Sharlyn J.
TI Binding of a Third Metal Ion by the Human Phosphatases PP2C alpha and
Wip1 Is Required for Phosphatase Activity
SO BIOCHEMISTRY
LA English
DT Article
ID DNA-DAMAGE RESPONSE; HUMAN PROTEIN PHOSPHATASE; SERINE/THREONINE
PHOSPHATASE; MYCOBACTERIUM-TUBERCULOSIS; 2C; GAMMA-H2AX; INSULIN;
ACTIVATION; SUBSTRATE; PATHWAYS
AB The PPM phosphatases require millimolar concentrations of Mg2+ or Mn2+ to activate phosphatase activity in vitro. The human phosphatases PP2C alpha (PPM1A) and Wip1 (PPM1D) differ in their physiological function, substrate specificity, and apparent metal affinity. A crystallographic structure of PP2C alpha shows only two metal ions in the active site. However, recent structural studies of several bacterial PP2C phosphatases have indicated three metal ions in the active site. Two residues that coordinate the third metal ion are highly conserved, suggesting that human PP2C phosphatases may also bind a third ion. Here, isothermal, titration calorimetry analysis of Mg2+ binding to PP2C alpha distinguished binding of two ions to high affinity sites from the binding of a third ion with a millimolar affinity, similar to the apparent metal affinity required for catalytic activity. Mutational analysis indicated that Asp239 and either Asp146 or Asp243 was required for low affinity binding of Mg2+, but that both Asp 146 and Asp239 were required for catalysis. Phosphatase activity assays in the presence of MgCl2, MnCl2, or mixtures of the two, demonstrate high phosphatase activity toward a phosphopeptide substrate when Mg2+ was bound to the low-affinity site, whether Mg2+ or Mn2+ ions were bound to the high affinity sites. Mutation of the corresponding putative third metal ion-coordinating residues of Wip1 affected catalytic activity similarly both in vitro and in human cells. These results suggest that phosphatase activity toward phosphopeptide substrates by PP2C alpha and Wip1 requires the binding of a Mg2+ ion to the low-affinity site.
C1 [Tanoue, Kan; Jenkins, Lisa M. Miller; Durell, Stewart R.; Debnath, Subrata; Sakai, Hiroyasu; Tagad, Harichandra D.; Ishida, Kazushige; Appella, Ettore; Mazur, Sharlyn J.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Mazur, SJ (reprint author), 37 Convent Dr,Bldg 37 Room 2140, Bethesda, MD 20892 USA.
EM mazurs@mail.nih.gov
FU Center for Center Research, National Cancer Institute, National
Institutes of Health
FX This research was supported by the Intramural Research Program of the
Center for Center Research, National Cancer Institute, National
Institutes of Health.
NR 59
TC 8
Z9 8
U1 0
U2 7
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD AUG 27
PY 2013
VL 52
IS 34
BP 5830
EP 5843
DI 10.1021/bi4005649
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 210EA
UT WOS:000323810900013
PM 23906386
ER
PT J
AU Ferguson, JF
Matthews, GJ
Townsend, RR
Raj, DS
Kanetsky, PA
Budoff, M
Fischer, MJ
Rosas, SE
Kanthety, R
Rahman, M
Master, SR
Qasim, A
Li, MY
Mehta, NN
Shen, HQ
Mitchell, BD
O'Connell, JR
Shuldiner, AR
Ho, WK
Young, R
Rasheed, A
Danesh, J
He, J
Kusek, JW
Ojo, AO
Flack, J
Go, AS
Gadegbeku, CA
Wright, JT
Saleheen, D
Feldman, HI
Rader, DJ
Foulkes, AS
Reilly, MP
AF Ferguson, Jane F.
Matthews, Gregory J.
Townsend, Raymond R.
Raj, Dominic S.
Kanetsky, Peter A.
Budoff, Matthew
Fischer, Michael J.
Rosas, Sylvia E.
Kanthety, Radhika
Rahman, Mahboob
Master, Stephen R.
Qasim, Atif
Li, Mingyao
Mehta, Nehal N.
Shen, Haiqing
Mitchell, Braxton D.
O'Connell, Jeffrey R.
Shuldiner, Alan R.
Ho, Weang Kee
Young, Robin
Rasheed, Asif
Danesh, John
He, Jiang
Kusek, John W.
Ojo, Akinlolu O.
Flack, John
Go, Alan S.
Gadegbeku, Crystal A.
Wright, Jackson T., Jr.
Saleheen, Danish
Feldman, Harold I.
Rader, Daniel J.
Foulkes, Andrea S.
Reilly, Muredach P.
CA CRIC Study Principal Investigators
TI Candidate Gene Association Study of Coronary Artery Calcification in
Chronic Kidney Disease Findings From the CRIC Study (Chronic Renal
Insufficiency Cohort)
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE candidate genes; chronic kidney disease (CKD); Chronic Renal
Insufficiency Cohort Study (CRIC); coronary artery calcification (CAC);
myocardial infarction (MI); risk factors; single nucleotide
polymorphisms (SNPs)
ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; MYOCARDIAL-INFARCTION;
COMMON VARIANTS; BLOOD-PRESSURE; HEART-DISEASE; CALCIUM;
ATHEROSCLEROSIS; HYPERTENSION; METAANALYSIS
AB Objectives This study sought to identify loci for coronary artery calcification (CAC) in patients with chronic kidney disease (CKD).
Background CKD is associated with increased CAC and subsequent coronary heart disease (CHD), but the mechanisms remain poorly defined. Genetic studies of CAC in CKD may provide a useful strategy for identifying novel pathways in CHD.
Methods We performed a candidate gene study (similar to 2,100 genes; similar to 50,000 single nucleotide polymorphisms [SNPs]) of CAC within the CRIC (Chronic Renal Insufficiency Cohort) study (N = 1,509; 57% European, 43% African ancestry). SNPs with preliminary evidence of association with CAC in CRIC were examined for association with CAC in the PennCAC (Penn Coronary Artery Calcification) (N = 2,560) and AFCS (Amish Family Calcification Study) (N = 784) samples. SNPs with suggestive replication were further analyzed for association with myocardial infarction (MI) in the PROMIS (Pakistan Risk of Myocardial Infarction Study) (N = 14,885).
Results Of 268 SNPs reaching p < 5 x 10(-4) for CAC in CRIC, 28 SNPs in 23 loci had nominal support (p < 0.05 and in same direction) for CAC in PennCAC or AFCS. Besides chr9p21 and COL4A1, known loci for CHD, these included SNPs having reported genome-wide association study association with hypertension (e. g., ATP2B1). In PROMIS, 4 of the 23 suggestive CAC loci (chr9p21, COL4A1, ATP2B1, and ABCA4) had significant associations with MI, consistent with their direction of effect on CAC.
Conclusions We identified several loci associated with CAC in CKD that also relate to MI in a general population sample. CKD imparts a high risk of CHD and may provide a useful setting for discovery of novel CHD genes and pathways. (C) 2013 by the American College of Cardiology Foundation
C1 [Ferguson, Jane F.; Qasim, Atif; Mehta, Nehal N.; Saleheen, Danish; Rader, Daniel J.; Reilly, Muredach P.] Univ Penn, Perelman Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA.
[Matthews, Gregory J.; Foulkes, Andrea S.] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Amherst, MA 01003 USA.
[Townsend, Raymond R.; Rosas, Sylvia E.; Feldman, Harold I.] Univ Penn, Renal Electrolyte & Hypertens Div, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Raj, Dominic S.] George Washington Univ, Med Fac Associates, Washington, DC USA.
[Kanetsky, Peter A.; Li, Mingyao; Feldman, Harold I.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Kanetsky, Peter A.; Li, Mingyao; Feldman, Harold I.] Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Budoff, Matthew] Los Angeles Biomed Res Inst, Torrance, CA USA.
[Fischer, Michael J.] Jesse Brown VA Med Ctr, Dept Med, Chicago, IL USA.
[Fischer, Michael J.] Univ Illinois Hosp & Hlth Sci Syst, Chicago, IL USA.
[Fischer, Michael J.] Edward Hines Jr VA Hosp, Ctr Management Complex Chron Care, Hines, IL USA.
[Kanthety, Radhika; Rahman, Mahboob] Case Western Reserve Univ, Dept Nephrol & Hypertens, Cleveland, OH 44106 USA.
[Master, Stephen R.] Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA USA.
[Shen, Haiqing; Mitchell, Braxton D.; O'Connell, Jeffrey R.; Shuldiner, Alan R.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
[Shuldiner, Alan R.] Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21218 USA.
[Ho, Weang Kee; Young, Robin; Danesh, John; Saleheen, Danish] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
[Rasheed, Asif; Saleheen, Danish] Ctr Noncommunicable Dis, Karachi, Pakistan.
[He, Jiang] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA USA.
[Kusek, John W.] NIDDK, Bethesda, MD USA.
[Ojo, Akinlolu O.] Univ Michigan, Sch Med, Ann Arbor, MI USA.
[Flack, John] Wayne State Univ, Sch Med, Dept Med, Detroit, MI 48201 USA.
[Go, Alan S.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA.
[Gadegbeku, Crystal A.] Temple Univ, Sch Med, Nephrol Sect, Dept Med, Philadelphia, PA 19122 USA.
[Wright, Jackson T., Jr.] Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA.
RP Reilly, MP (reprint author), Univ Penn, Perelman Sch Med, 11-136 Translat Res Bldg,3400 Civ Ctr Blvd,Bldg 4, Philadelphia, PA 19104 USA.
RI Ferguson, Jane/C-7154-2011;
OI Ferguson, Jane/0000-0001-6896-1025; HO, WEANG KEE/0000-0002-8269-7344;
Mitchell, Braxton/0000-0003-4920-4744
FU National Institute of Diabetes and Digestive and Kidney Diseases
[5U01DK060990, 5U01DK060984, 5U01DK06102, 5U01DK061021, 5U01DK061028,
5U01DK60980, 5U01DK060963, 5U01DK060902]; National Institutes of Health
(NIH) [UL1RR024134, UL1RR025005, M01RR16500, UL1RR024989, M01RR000042,
UL1RR024986, UL1RR029879, RR05096, UL1RR024131]; National Institutes of
Health Research [R01-HL69313, U01-HL72515, R01-HL088119]; American Heart
Association Scientist Development Grant [0830146N]; Mid-Atlantic
Nutrition and Obesity Research Center [P30 DK072488]; University of
Cambridge; Center for Non-Communicable Diseases, Pakistan; Wellcome
Trust; Department of Veterans Affairs Health Services Research and
Development Service; Clinical and Translational Science Award
[UL1RR024134]; Diabetes and Endocrine Research Center from the NIH
[P20-DK 019525]; Abbott; Reata Laboratoriea; British Heart Foundation;
UK Medical Research Council; U.S. National Institutes of Health; Fogarty
Foundation; UK National Institute of Health Research, Cambridge;
Biomedical Research Centre; Pfizer; European Commission; Medtronics;
GlaxoSmithKline; Merck Research Laboratories; Virginia Brown Fellowship
for Aging and Stroke Research; NIH [K24-HL107643, R01-DK090505,
U01-HL108636, R01-HL113147]; [R01-DK071224]; [R01-HL107196]
FX The CRIC study is supported by cooperative agreements 5U01DK060990,
5U01DK060984, 5U01DK06102, 5U01DK061021, 5U01DK061028, 5U01DK60980,
5U01DK060963, and 5U01DK060902 from the National Institute of Diabetes
and Digestive and Kidney Diseases and by grants UL1RR024134,
UL1RR025005, M01RR16500, UL1RR024989, M01RR000042, UL1RR024986,
UL1RR029879, RR05096, and UL1RR024131 from the National Institutes of
Health (NIH). This work was supported by R01-DK071224 (to Dr. Reilly).
The Amish Calcification Study was supported by National Institutes of
Health Research Grants R01-HL69313, U01-HL72515, and R01-HL088119, and
an American Heart Association Scientist Development Grant (0830146N).
Partial funding was also provided by the Mid-Atlantic Nutrition and
Obesity Research Center (P30 DK072488). Fieldwork in PROMIS was
supported by grants available to investigators at the University of
Cambridge and at the Center for Non-Communicable Diseases, Pakistan.
Genotyping in PROMIS was supported by Wellcome Trust. Dr. Fischer is
supported by a Department of Veterans Affairs Health Services Research
and Development Service (Career Development Award). Dr. Foulkes is
supported by R01-HL107196. PennCAC was supported by a Clinical and
Translational Science Award (UL1RR024134) and a Diabetes and Endocrine
Research Center (P20-DK 019525) award (both from the NIH to the
University of Pennsylvania). Dr. Rosas has received grants from Abbott
and Reata Laboratoriea. Dr. Danesh has received research funding from
the British Heart Foundation, UK Medical Research Council, Wellcome
Trust, U.S. National Institutes of Health, Fogarty Foundation, UK
National Institute of Health Research, Cambridge, Biomedical Research
Centre, Pfizer, and European Commission. Dr. Wright Jr. has received
grant support funding and served on the advisory board for Medtronics.
Dr. Reilly has received research grant support from GlaxoSmithKline and
Merck Research Laboratories; and is supported by a Virginia Brown
Fellowship for Aging and Stroke Research; by K24-HL107643, R01-DK090505,
U01-HL108636, and R01-HL113147 from the NIH. All other authors have
reported that they have no relationships relevant to the contents of
this paper to disclose.
NR 52
TC 12
Z9 12
U1 3
U2 13
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD AUG 27
PY 2013
VL 62
IS 9
BP 789
EP 798
DI 10.1016/j.jacc.2013.01.103
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 211IL
UT WOS:000323899900005
PM 23727086
ER
PT J
AU Wang, MG
Arteaga, D
He, BJJ
AF Wang, Megan
Arteaga, Daniel
He, Biyu J.
TI Brain mechanisms for simple perception and bistable perception
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE visual perception; fMRI; MVPA; Granger causality; ambiguous images
ID PRIMARY VISUAL-CORTEX; LATERAL GENICULATE-NUCLEUS; BINOCULAR-RIVALRY;
AMBIGUOUS FIGURES; NEURAL ACTIVITY; CORTICAL RESPONSES;
BAYESIAN-INFERENCE; PREFRONTAL CORTEX; PARIETAL CORTEX; WORKING-MEMORY
AB When faced with ambiguous sensory inputs, subjective perception alternates between the different interpretations in a stochastic manner. Such multistable perception phenomena have intrigued scientists and laymen alike for over a century. Despite rigorous investigations, the underlying mechanisms of multistable perception remain elusive. Recent studies using multivariate pattern analysis revealed that activity patterns in posterior visual areas correlate with fluctuating percepts. However, increasing evidence suggests that vision-and perception at large-is an active inferential process involving hierarchical brain systems. We applied searchlight multivariate pattern analysis to functional magnetic resonance imaging signals across the human brain to decode perceptual content during bistable perception and simple unambiguous perception. Although perceptually reflective activity patterns during simple perception localized predominantly to posterior visual regions, bistable perception involved additionally many higher-order frontoparietal and temporal regions. Moreover, compared with simple perception, both top-down and bottom-up influences were dramatically enhanced during bistable perception. We further studied the intermittent presentation of ambiguous images-a condition that is known to elicit perceptual memory. Compared with continuous presentation, intermittent presentation recruited even more higher-order regions and was accompanied by further strengthened top-down influences but relatively weakened bottom-up influences. Taken together, these results strongly support an active top-down inferential process in perception.
C1 [Wang, Megan; Arteaga, Daniel; He, Biyu J.] NINDS, NIH, Bethesda, MD 20892 USA.
RP He, BJJ (reprint author), NINDS, NIH, Bethesda, MD 20892 USA.
EM biyu.he@nih.gov
OI He, Biyu/0000-0003-1549-1351
FU National Institutes of Health, National Institute of Neurological
Disorders and Stroke
FX We thank David Leopold and Panagiota Theodoni for comments on a previous
draft of the manuscript and Avi Snyder and Don Zhang for sharing
cortical parcellation ROIs. This research was supported by the
Intramural Research Program of the National Institutes of Health,
National Institute of Neurological Disorders and Stroke.
NR 90
TC 10
Z9 12
U1 1
U2 25
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 AUG 27
PY 2013
VL 110
IS 35
BP E3350
EP E3359
DI 10.1073/pnas.1221945110
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 206ZC
UT WOS:000323564600014
PM 23942129
ER
PT J
AU Lavine, JS
King, AA
Andreasen, V
Bjornstad, ON
AF Lavine, Jennie S.
King, Aaron A.
Andreasen, Viggo
Bjornstad, Ottar N.
TI Immune Boosting Explains Regime-Shifts in Prevaccine-Era Pertussis
Dynamics
SO PLOS ONE
LA English
DT Article
ID BORDETELLA-PERTUSSIS; CHILDHOOD DISEASES; VACCINATION; EPIDEMIOLOGY;
TRANSMISSION; INFERENCE; INTERFERENCE; POPULATIONS; INFECTIONS; INFANTS
AB Understanding the biological mechanisms underlying episodic outbreaks of infectious diseases is one of mathematical epidemiology's major goals. Historic records are an invaluable source of information in this enterprise. Pertussis (whooping cough) is a re-emerging infection whose intermittent bouts of large multiannual epidemics interspersed between periods of smaller-amplitude cycles remain an enigma. It has been suggested that recent increases in pertussis incidence and shifts in the age-distribution of cases may be due to diminished natural immune boosting. Here we show that a model that incorporates this mechanism can account for a unique set of pre-vaccine-era data from Copenhagen. Under this model, immune boosting induces transient bursts of large amplitude outbreaks. In the face of mass vaccination, the boosting model predicts larger and more frequent outbreaks than do models with permanent or passively-waning immunity. Our results emphasize the importance of understanding the mechanisms responsible for maintaining immune memory for pertussis epidemiology.
C1 [Lavine, Jennie S.; King, Aaron A.] Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA.
[Lavine, Jennie S.; King, Aaron A.; Andreasen, Viggo; Bjornstad, Ottar N.] NIH, Fogarty Int Ctr, Bethesdsa, MD USA.
[King, Aaron A.] Univ Michigan, Dept Math, Ann Arbor, MI 48109 USA.
[King, Aaron A.] Univ Michigan, Ctr Study Complex Syst, Ann Arbor, MI 48109 USA.
[Andreasen, Viggo] Roskilde Univ, Dept Sci Syst & Models, Roskilde, Denmark.
[Bjornstad, Ottar N.] Penn State Univ, Dept Entomol & Biol, University Pk, PA 16802 USA.
RP King, AA (reprint author), Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA.
EM kingaa@umich.edu
RI King, Aaron/B-8092-2012
OI King, Aaron/0000-0001-6159-3207
FU Research and Policy for Infectious Disease Dynamics program of the
Science and Technology Directorate, U.S. Department of Homeland
Security; Fogarty International Center, U.S. National Institutes of
Health; National Institutes of Health [1-R01-AI-101155-01]; Danish
Medical Research Council [272-06-0430]; Bill & Melinda Gates Foundation
FX Financial support was provided by the Research and Policy for Infectious
Disease Dynamics program of the Science and Technology Directorate, U.S.
Department of Homeland Security and Fogarty International Center, U.S.
National Institutes of Health, and by grants from the National
Institutes of Health (grant #1-R01-AI-101155-01 to AAK), the Danish
Medical Research Council (grant #272-06-0430 to VA), and the Bill &
Melinda Gates Foundation (to ONB). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 43
TC 10
Z9 10
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 AUG 26
PY 2013
VL 8
IS 8
AR e72086
DI 10.1371/journal.pone.0072086
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 215RU
UT WOS:000324228800044
PM 23991047
ER
PT J
AU Sharma, A
Berga-Bolanos, R
Sultana, DA
Sen, JM
AF Sharma, Archna
Berga-Bolanos, Rosa
Sultana, Dil Afroz
Sen, Jyoti Misra
TI IL-4 and IL-4 Receptor Expression Is Dispensable for the Development and
Function of Natural Killer T Cells
SO PLOS ONE
LA English
DT Article
ID NKT CELLS; IMMUNE-SYSTEM; TRANSCRIPTION; LINEAGE; DIFFERENTIATION;
PROGRAM; INTERLEUKIN-4; ACTIVATION; ANTI-CD3; SUBSETS
AB CD4 T cells acquire functional properties including cytokine production upon antigenic stimulation through the T cell receptor (TCR) and differentiate into T helper (Th) cells. Th1 cells produce interferon (IFN)-gamma and Th2 cells produce interleukin (IL)-4. Th1 and 2 cells utilize IFN-gamma and IL-4 for further maturation and maintenance, respectively. Promyelocytic leukemia zinc finger (PLZF)-expressing invariant natural killer T (iNKT) cells develop in the thymus and acquire functional ability to produce IL-4 and IFN-gamma in the thymus in the absence of antigenic stimulation. In response to antigenic stimulation, iNKT cells rapidly produce IFN-gamma and IL-4. However, it is still unknown as to whether iNKT cells require these cytokines for maturation or survival in vivo. In this study, using IL-4- and IL-4 receptor-(IL-4R) deficient mice, we demonstrate that IL-4 as well as IL-4R expression is dispensable for the development, function and maintenance of iNKT cells.
C1 [Sharma, Archna; Berga-Bolanos, Rosa; Sultana, Dil Afroz; Sen, Jyoti Misra] NIA, Immune Cells & Inflammat Sect, NIH, Baltimore, MD 21224 USA.
RP Sen, JM (reprint author), NIA, Immune Cells & Inflammat Sect, NIH, Baltimore, MD 21224 USA.
EM Jyoti-Sen@nih.gov
RI Sharma, Archna/R-9377-2016
OI Sharma, Archna/0000-0003-4745-0220
FU National Institute on Aging at the National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institute on Aging at 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 29
TC 2
Z9 3
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 26
PY 2013
VL 8
IS 8
AR e71872
DI 10.1371/journal.pone.0071872
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 215RU
UT WOS:000324228800022
PM 23990998
ER
PT J
AU Siebenhuhner, F
Weiss, SA
Coppola, R
Weinberger, DR
Bassett, DS
AF Siebenhuehner, Felix
Weiss, Shennan A.
Coppola, Richard
Weinberger, Daniel R.
Bassett, Danielle S.
TI Intra- and Inter-Frequency Brain Network Structure in Health and
Schizophrenia
SO PLOS ONE
LA English
DT Article
ID SMALL-WORLD NETWORKS; NEURAL MASS MODEL; GRAPH-THEORETICAL ANALYSIS;
SPACE SEPARATION METHOD; TIME-SERIES ANALYSIS; FUNCTIONAL NETWORKS;
WORKING-MEMORY; INTERMEDIATE PHENOTYPES; SYNAPTIC PLASTICITY;
CONNECTIVITY
AB Empirical studies over the past two decades have provided support for the hypothesis that schizophrenia is characterized by altered connectivity patterns in functional brain networks. These alterations have been proposed as genetically mediated diagnostic biomarkers and are thought to underlie altered cognitive functions such as working memory. However, the nature of this dysconnectivity remains far from understood. In this study, we perform an extensive analysis of functional connectivity patterns extracted from MEG data in 14 subjects with schizophrenia and 14 healthy controls during a 2-back working memory task. We investigate uni-, bi- and multivariate properties of sensor time series by computing wavelet entropy of and correlation between time series, and by constructing binary networks of functional connectivity both within and between classical frequency bands (gamma, beta, alpha, and theta). Networks are based on the mutual information between wavelet time series, and estimated for each trial window separately, enabling us to consider both network topology and network dynamics. We observed significant decreases in time series entropy and significant increases in functional connectivity in the schizophrenia group in comparison to the healthy controls and identified an inverse relationship between these measures across both subjects and sensors that varied over frequency bands and was more pronounced in controls than in patients. The topological organization of connectivity was altered in schizophrenia specifically in high frequency c and b band networks as well as in the gamma-beta cross-frequency networks. Network topology varied over trials to a greater extent in patients than in controls, suggesting disease-associated alterations in dynamic network properties of brain function. Our results identify signatures of aberrant neurophysiological behavior in schizophrenia across uni-, bi- and multivariate scales and lay the groundwork for further clinical studies that might lead to the discovery of new intermediate phenotypes.
C1 [Siebenhuehner, Felix; Bassett, Danielle S.] Univ Calif Santa Barbara, Dept Phys, Santa Barbara, CA 93106 USA.
[Siebenhuehner, Felix] Univ Helsinki, Ctr Neurosci, Helsinki, Finland.
[Weiss, Shennan A.] Columbia Univ, Dept Neurol, New York, NY USA.
[Coppola, Richard] NIMH, MEG Core Facil, Bethesda, MD 20892 USA.
[Weinberger, Daniel R.] NIMH, Genes Cognit & Psychosis Program, Clin Brain Disorders Branch, Bethesda, MD 20892 USA.
[Weinberger, Daniel R.] Lieber Inst Brain Dev, Baltimore, MD USA.
[Bassett, Danielle S.] Univ Calif Santa Barbara, Sage Ctr Study Mind, Santa Barbara, CA 93106 USA.
RP Bassett, DS (reprint author), Univ Calif Santa Barbara, Dept Phys, Santa Barbara, CA 93106 USA.
EM dbassett@physics.ucsb.edu
FU Errett Fisher Foundation; Templeton Foundation; David and Lucile Packard
Foundation; Public Health Service [NS44393]; Sage Center for the Study
of the Mind; Institute for Collaborative Biotechnologies from the U.S.
Army Research Oce [W911NF-09-D-0001]; Center for Scientic Computing at
the California NanoSystems Institute and Materials Research Laboratory:
a National Science Foundation (NSF) MRSEC [DMR-1121053]; NSF
[CNS-0960316]; Weinberger Lab; National Institute of Mental Health
Magnetoencephalography core facility
FX This work was supported by the Errett Fisher Foundation, the Templeton
Foundation, the David and Lucile Packard Foundation, Public Health
Service Grant NS44393, Sage Center for the Study of the Mind, and the
Institute for Collaborative Biotechnologies through contract no.
W911NF-09-D-0001 from the U.S. Army Research Oce. The authors
acknowledge support from the Center for Scientic Computing at the
California NanoSystems Institute and Materials Research Laboratory: a
National Science Foundation (NSF) MRSEC (DMR-1121053) and NSF
CNS-0960316. The patients and normal controls were studied as part of
the Clinical Brain Disorders Branch Sibling study (D.R. Weinberger PI),
an investigation of the biological components of genetic risk for
schizophrenia, with direct funding of the Weinberger Lab and the
National Institute of Mental Health Magnetoencephalography core facility
(R. Coppola). The content is solely the responsibility of the authors
and does not necessarily represent the official views of any of the
funding agencies. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 140
TC 14
Z9 14
U1 3
U2 20
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 AUG 26
PY 2013
VL 8
IS 8
AR e72351
DI 10.1371/journal.pone.0072351
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 215RU
UT WOS:000324228800062
PM 23991097
ER
PT J
AU Kassis, JA
Lilly, MA
AF Kassis, Judith A.
Lilly, Mary A.
TI PRC2 Goes Solo in the Drosophila Female Germline
SO DEVELOPMENTAL CELL
LA English
DT Editorial Material
ID POLYCOMB; TARGETS; ELEGANS; CELLS
AB Polycomb-group proteins silence gene expression through epigenetic modification of chromatin. In this issue of Developmental Cell, I ovino et al. (2013) demonstrate that Polycomb repressive complex 2 (PRC2) is required for maintenance of oocyte fate by repressing expression of two critical targets, Cyclin E and dacapo, during the early meiotic cycle.
C1 [Kassis, Judith A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
[Lilly, Mary A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
RP Kassis, JA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
EM jkassis@mail.nih.gov; lillym@helix.nih.gov
FU Intramural NIH HHS [ZIA HD001613-15]
NR 10
TC 0
Z9 0
U1 0
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1534-5807
J9 DEV CELL
JI Dev. Cell
PD AUG 26
PY 2013
VL 26
IS 4
BP 329
EP 330
DI 10.1016/j.devcel.2013.08.008
PG 2
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 210RH
UT WOS:000323851700003
PM 23987509
ER
PT J
AU Park, JH
Kang, HJ
Kang, SI
Lee, JE
Hur, J
Ge, K
Mueller, E
Li, H
Lee, BC
Lee, SB
AF Park, Jun Hong
Kang, Hong Jun
Kang, Soo Im
Lee, Ji Eun
Hur, Jamie
Ge, Kai
Mueller, Elisabetta
Li, Hongjie
Lee, Byeong-Chel
Lee, Sean Bong
TI A Multifunctional Protein, EWS, Is Essential for Early Brown Fat Lineage
Determination
SO DEVELOPMENTAL CELL
LA English
DT Article
ID RNA-BINDING PROTEIN; SARCOMA GENE EWS; ADIPOSE-TISSUE; ADIPOCYTE
DIFFERENTIATION; ONCOGENIC TRANSFORMATION; TRANSCRIPTIONAL CONTROL;
ENERGY-EXPENDITURE; MYXOID LIPOSARCOMA; EWINGS-SARCOMA; ADULT HUMANS
AB The recent surge in obesity has provided an impetus to better understand the mechanisms of adipogenesis, particularly in brown adipose tissue (BAT) because of its potential utilization for antiobesity therapy. Postnatal brown adipocytes arise from early muscle progenitors, but how brown fat lineage is determined is not completely understood. Here, we show that a multifunctional protein, Ewing Sarcoma (EWS), is essential for determining brown fat lineage during development. BATs from Ews null embryos and newborns are developmentally arrested. Ews mutant brown preadipocytes fail to differentiate due to loss of Bmp7 expression, a critical early brown adipogenic factor. We demonstrate that EWS, along with its binding partner Y-box binding protein 1 (YBX1), activates Bmp7 transcription. Depletion of either Ews or Ybx1 leads to loss of Bmp7 expression and brown adipogenesis. Remarkably, Ews null BATs and brown preadipocytes ectopically express myogenic genes. These results demonstrate that EWS is essential for early brown fat lineage determination.
C1 [Park, Jun Hong; Kang, Hong Jun; Kang, Soo Im; Hur, Jamie; Mueller, Elisabetta; Li, Hongjie; Lee, Byeong-Chel; Lee, Sean Bong] NIDDK, Genet Dev & Dis Branch, Bethesda, MD 20892 USA.
[Lee, Ji Eun; Ge, Kai] NIDDK, Mol Endocrinol Branch, Bethesda, MD 20892 USA.
[Lee, Byeong-Chel] Univ Pittsburgh, Inst Canc, Dept Med, Pittsburgh, PA 15213 USA.
[Lee, Sean Bong] Tulane Univ, Sch Med, Dept Pathol & Lab Med, New Orleans, LA 70112 USA.
RP Lee, SB (reprint author), NIDDK, Genet Dev & Dis Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM slee30@tulane.edu
RI Lee, Ji-Eun/F-7891-2011;
OI Lee, Ji-Eun/0000-0002-3768-7016; Ge, Kai/0000-0002-7442-5138
FU Intramural Research Program of the NIDDK, NIH; Tulane University
FX We thank Raimund Hirschberg (Los Angeles Biomedical Research Institute)
for providing the murine Bmp7 promoter-Luc plasmids; Huiyan Lu (NIDDK)
for in vitro fertilization and generation of the Ews mutant
129SvEv/Black Swiss strain; Oksana Gavrilova (NIDDK) for the
temperature-controlled chamber; Sandra E. Dunn (University of British
Columbia), Alexandra McPherron and Yun Kyung Lee (NIDDK), and Hyeog Kang
(NHLBI) for helpful discussions; and Jan Endlich (JFE Enterprises) for
TEM. This research was supported in part by the Intramural Research
Program of the NIDDK, NIH, and by startup funds from Tulane University
(to S.B.L.). J.H.P., H.J.K., S.I.K., J.H., and H.L. performed
experiments; J.E.L., K.G., E.M., and B.-C.L. contributed critical
reagents and suggestions; and J.H.P. and S.B.L. designed experiments,
analyzed data, and wrote the manuscript.
NR 46
TC 26
Z9 26
U1 0
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1534-5807
J9 DEV CELL
JI Dev. Cell
PD AUG 26
PY 2013
VL 26
IS 4
BP 393
EP 404
DI 10.1016/j.devcel.2013.07.002
PG 12
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 210RH
UT WOS:000323851700009
PM 23987512
ER
PT J
AU Molle, C
Zhang, T
de Lendonck, LY
Gueydan, C
Andrianne, M
Sherer, F
Van Simaeys, G
Blackshear, PJ
Leo, O
Goriely, S
AF Molle, Celine
Zhang, Tong
de Lendonck, Laure Ysebrant
Gueydan, Cyril
Andrianne, Mathieu
Sherer, Felicie
Van Simaeys, Gaetan
Blackshear, Perry J.
Leo, Oberdan
Goriely, Stanislas
TI Tristetraprolin regulation of interleukin 23 mRNA stability prevents a
spontaneous inflammatory disease
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID NECROSIS-FACTOR-ALPHA; DENDRITIC CELLS; EPIDERMAL HYPERPLASIA;
DEFICIENCY SYNDROME; TNF-ALPHA; IL-23; EXPRESSION; DEADENYLATION;
DESTABILIZATION; PATHOGENESIS
AB Interleukin (IL) 12 and IL23 are two related heterodimeric cytokines produced by antigen-presenting cells. The balance between these two cytokines plays a crucial role in the control of Th1/Th17 responses and autoimmune inflammation. Most studies focused on their transcriptional regulation. Herein, we explored the role of the adenine and uridine-rich element (ARE)-binding protein tristetraprolin (TTP) in influencing mRNA stability of IL12p35, IL12/23p40, and IL23p19 subunits. LPS-stimulated bone marrow-derived dendritic cells (BMDCs) from TTP-/- mice produced normal levels of IL12/23p40. Production of IL12p70 was modestly increased in these conditions. In contrast, we observed a strong impact of TTP on IL23 production and IL23p19 mRNA stability through several AREs in the 3' untranslated region. TTP-/- mice spontaneously develop an inflammatory syndrome characterized by cachexia, myeloid hyperplasia, dermatitis, and erosive arthritis. We observed IL23p19 expression within skin lesions associated with exacerbated IL17A and IL22 production by infiltrating gamma delta T cells and draining lymph node CD4 T cells. We demonstrate that the clinical and immunological parameters associated with TTP deficiency were completely dependent on the IL23-IL17A axis. We conclude that tight control of IL23 mRNA stability by TTP is critical to avoid severe inflammation.
C1 [Molle, Celine; Zhang, Tong; de Lendonck, Laure Ysebrant; Andrianne, Mathieu; Leo, Oberdan; Goriely, Stanislas] Univ Libre Brussels, IMI, B-6041 Gosselies, Belgium.
[Gueydan, Cyril] Univ Libre Brussels, Lab Biol Mol Gene, B-6041 Gosselies, Belgium.
[Sherer, Felicie; Van Simaeys, Gaetan] Univ Libre Brussels, CMMI, B-6041 Gosselies, Belgium.
[Sherer, Felicie; Van Simaeys, Gaetan] Univ Libre Brussels, Hop Erasme, Dept Nucl Med, B-1070 Brussels, Belgium.
[Blackshear, Perry J.] Natl Inst Environm Hlth, Lab Signal Transduct, Natl Inst Hlth Sci, Res Triangle Pk, NC 27709 USA.
[Blackshear, Perry J.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
[Blackshear, Perry J.] Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA.
[Goriely, Stanislas] WELBIO, B-6041 Gosselies, Belgium.
RP Goriely, S (reprint author), Univ Libre Brussels, IMI, B-6041 Gosselies, Belgium.
EM stgoriel@ulb.ac.be
OI Goriely, Stanislas/0000-0002-7005-6195; Gueydan,
Cyril/0000-0003-3097-7667
FU government of the Walloon Region; GlaxoSmithKline Biologicals; Fonds
National de la Recherche Scientifique (FRS-FNRS, Belgium); WELBIO;
Interuniversity Attraction Pole of the Belgian Federal Science Policy;
Televie. S. Goriely is a research associate of the FRS-FNRS; Intramural
Research Program of the NIEHS, NIH
FX The Institute for Medical Immunology is sponsored by the government of
the Walloon Region and GlaxoSmithKline Biologicals. This study was
supported by the Fonds National de la Recherche Scientifique (FRS-FNRS,
Belgium), the WELBIO, and an Interuniversity Attraction Pole of the
Belgian Federal Science Policy. C. Molle is a postdoctoral fellow of the
FRS-FNRS. L. Ysebrant and M. Andrianne are supported by a grant from the
Televie. S. Goriely is a research associate of the FRS-FNRS.; P.J.
Blackshear is supported by the Intramural Research Program of the NIEHS,
NIH.
NR 35
TC 24
Z9 24
U1 0
U2 12
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD AUG 26
PY 2013
VL 210
IS 9
BP 1675
EP 1684
DI 10.1084/jem.20120707
PG 10
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 207ZV
UT WOS:000323644800005
PM 23940256
ER
PT J
AU Zou, WG
Greenblatt, MB
Brady, N
Lotinun, S
Zhai, B
de Rivera, H
Singh, A
Sun, J
Gygi, SP
Baron, R
Glimcher, LH
Jones, DC
AF Zou, Weiguo
Greenblatt, Matthew B.
Brady, Nicholas
Lotinun, Sutada
Zhai, Bo
de Rivera, Heather
Singh, Anju
Sun, Jun
Gygi, Steven P.
Baron, Roland
Glimcher, Laurie H.
Jones, Dallas C.
TI The microtubule-associated protein DCAMKL1 regulates osteoblast function
via repression of Runx2
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID DOUBLECORTIN-LIKE-KINASE; CLEIDOCRANIAL DYSPLASIA; SERINE
PHOSPHORYLATION; TRANSCRIPTION FACTOR; SKELETAL DEVELOPMENT; NEURONAL
MIGRATION; BONE-FORMATION; STEM-CELL; MASS; DIFFERENTIATION
AB Osteoblasts are responsible for the formation and mineralization of the skeleton. To identify novel regulators of osteoblast differentiation, we conducted an unbiased forward genetic screen using a lentiviral-based shRNA library. This functional genomics analysis led to the identification of the microtubule-associated protein DCAMKL1 (Doublecortin-like and CAM kinase-like 1) as a novel regulator of osteogenesis. Mice with a targeted disruption of Dcamkl1 displayed elevated bone mass secondary to increased bone formation by osteoblasts. Molecular experiments demonstrated that DCAMKL1 represses osteoblast activation by antagonizing Runx2, the master transcription factor in osteoblasts. Key elements of the cleidocranial dysplasia phenotype observed in Runx2(+/-) mice are reversed by the introduction of a Dcamkl1-null allele. Our results establish a genetic linkage between these two proteins in vivo and demonstrate that DCAMKL1 is a physiologically relevant regulator of anabolic bone formation.
C1 [Zou, Weiguo; Sun, Jun] Chinese Acad Sci, State Key Lab Cell Biol, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China.
[Greenblatt, Matthew B.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Brady, Nicholas; de Rivera, Heather; Glimcher, Laurie H.] Weill Cornell Med Coll, Dept Med, New York, NY 10065 USA.
[Lotinun, Sutada; Baron, Roland] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA.
[Zhai, Bo; Gygi, Steven P.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
Harvard Univ, Boston, MA 02115 USA.
[Singh, Anju] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
[Jones, Dallas C.] Merck Res Labs, Boston, MA 02115 USA.
RP Zou, WG (reprint author), Chinese Acad Sci, State Key Lab Cell Biol, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China.
EM zouwg94@sibcb.ac.cn
OI Brady, Nicholas/0000-0002-2928-0232
FU National Institutes of Health [HD055601, K99AR055668]; Merck
Pharmaceuticals; Thousand Young Talents Program of the Chinese
government
FX This work is supported by National Institutes of Health grants HD055601
(to L.H. Glimcher) and K99AR055668 (to D.C. Jones) and a grant from
Merck Pharmaceuticals. W. Zou is a recipient of the Thousand Young
Talents Program of the Chinese government.
NR 47
TC 10
Z9 10
U1 2
U2 10
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD AUG 26
PY 2013
VL 210
IS 9
BP 1793
EP 1806
DI 10.1084/jem.20111790
PG 14
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 207ZV
UT WOS:000323644800013
PM 23918955
ER
PT J
AU Rytty, R
Nikkinen, J
Paavola, L
Abou Elseoud, A
Moilanen, V
Visuri, A
Tervonen, O
Renton, AE
Traynor, BJ
Kiviniemi, V
Remes, AM
AF Rytty, Riikka
Nikkinen, Juha
Paavola, Liisa
Abou Elseoud, Ahmed
Moilanen, Virpi
Visuri, Annina
Tervonen, Osmo
Renton, Alan E.
Traynor, Bryan J.
Kiviniemi, Vesa
Remes, Anne M.
TI GroupICA dual regression analysis of resting state networks in a
behavioral variant of forntotemporal dementia
SO FRONTIERS IN HUMAN NEUROSCIENCE
LA English
DT Article
DE default; resting state; functional MRI; dorsal attention network;
frontotemporal dementia
ID INDEPENDENT COMPONENT ANALYSIS; FRONTOTEMPORAL DEMENTIA;
ALZHEIMERS-DISEASE; BRAIN ACTIVITY; FUNCTIONAL CONNECTIVITY;
DIAGNOSTIC-CRITERIA; DEFAULT-MODE; GROUP PICA; MR-IMAGES; FMRI
AB Functional MRI studies have revealed changes in default-mode and salience networks in neurodegenerative dementias, especially in Alzheimer's disease (AD). The purpose of this study was to analyze the whole brain cortex resting state networks (RSNs) in patients with behavioral variant frontotemporal dementia (bvFTD) by using resting state functional MRI (rfMRI). The group specific RSNs were identified by high model order independent component analysis (ICA) and a dual regression technique was used to detect between-group differences in the RSNs with p < 0.05 threshold corrected for multiple comparisons. A y-concatenation method was used to correct for multiple comparisons for multiple independent components, gray matter differences as well as the voxel level. We found increased connectivity in several networks within patients with bvFTD compared to the control group. The most prominent enhancement was seen in the right frontotemporal area and insula. A significant increase in functional connectivity was also detected in the left dorsal attention network (DAN), in anterior paracingulate-a default mode sub-network as well as in the anterior parts of the frontal pole. Notably the increased patterns of connectivity were seen in areas around atrophic regions. The present results demonstrate abnormal increased connectivity in several important brain networks including the DAN and default-mode network (DMN) in patients with bvFTD. These changes may be associated with decline in executive functions and attention as well as apathy, which are the major cognitive and neuropsychiatric defects in patients with frontotemporal dementia.
C1 [Rytty, Riikka; Paavola, Liisa; Visuri, Annina] Univ Oulu, Inst Clin Med, Dept Neurol, Oulu, Finland.
[Rytty, Riikka; Paavola, Liisa; Moilanen, Virpi] Oulu Univ Hosp, Dept Neurol, Oulu, Finland.
[Nikkinen, Juha; Abou Elseoud, Ahmed; Tervonen, Osmo; Kiviniemi, Vesa] Univ Oulu, Inst Clin Med, Dept Radiol, Oulu, Finland.
[Renton, Alan E.; Traynor, Bryan J.] NIA, Neuromuscular Dis Res Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Remes, Anne M.] Univ Eastern Finland, Inst Clin Med, Dept Neurol, Kuopio 70211, Finland.
[Remes, Anne M.] Kuopio Univ Hosp, Dept Neurol, SF-70210 Kuopio, Finland.
RP Remes, AM (reprint author), Univ Eastern Finland, Inst Clin Med, Dept Neurol, Yliopistonranta 1,POB 1627, Kuopio 70211, Finland.
EM anne.remes@uef.fi
RI Traynor, Bryan/G-5690-2010
FU Finnish Academy [117111, 123772]; Finnish Medical Foundation; Finnish
Neurological Foundation; Oulu University Hospital; National Graduate
School of Clinical Investigation; Intramural Research Programs of the
NIH; National Institute on Aging [Z01-AG000949-02]; ALS Association;
AriSLA; Packard Center for ALS research; FIGC; Microsoft Research (Bryan
J. Traynor); Myasthenia Gravis Foundation
FX This work was supported by grants from the Finnish Academy [grants
117111 and 123772 (Vesa Kiviniemi)], Finnish Medical Foundation (Vesa
Kiviniemi, Anne M. Remes), Finnish Neurological Foundation (Vesa
Kiviniemi), KEVO grants from Oulu University Hospital (Vesa Kiviniemi,
Anne M. Remes), National Graduate School of Clinical Investigation
(Riikka Rytty), the Intramural Research Programs of the NIH, and
National Institute on Aging (Z01-AG000949-02)(Bryan J. Traynor) the ALS
Association, AriSLA, Packard Center for ALS research, FIGC, Microsoft
Research (Bryan J. Traynor), and the Myasthenia Gravis Foundation (Bryan
J. Traynor).
NR 50
TC 12
Z9 12
U1 0
U2 16
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1662-5161
J9 FRONT HUM NEUROSCI
JI Front. Hum. Neurosci.
PD AUG 26
PY 2013
VL 7
DI 10.3389/fnhum.2013.00461
PG 10
WC Neurosciences; Psychology
SC Neurosciences & Neurology; Psychology
GA 205XD
UT WOS:000323477200001
ER
PT J
AU Simons, SS
Kumar, R
AF Simons, S. Stoney, Jr.
Kumar, Raj
TI Variable steroid receptor responses: Intrinsically disordered AF1 is the
key
SO MOLECULAR AND CELLULAR ENDOCRINOLOGY
LA English
DT Review
DE Steroid receptors; Selectivity in controlling gene expression;
Intrinsically disordered domains; Selective receptor modulators (SRMs);
A(max) and EC50; AF1 domain as a molecular rheostat
ID LIGAND-BINDING DOMAIN; GLUCOCORTICOID-RECEPTOR; ESTROGEN-RECEPTOR;
GENE-EXPRESSION; ANDROGEN RECEPTOR; ACTIVATION DOMAINS; HORMONE
RECEPTORS; PROSTATE-CANCER; TERMINAL DOMAIN; TRANSCRIPTION
AB Steroid hormones, acting through their cognate receptor proteins, see widespread clinical applications due to their ability to alter the induction or repression of numerous genes. However, steroid usage is limited by the current inability to control off-target, or non-specific, side-effects. Recent results from three separate areas of research with glucocorticoid and other steroid receptors (cofactor-induced changes in receptor structure, the ability of ligands to alter remote regions of receptor structure, and how cofactor concentration affects both ligand potency and efficacy) indicate that a key element of receptor activity is the intrinsically disordered amino-terminal domain. These results are combined to construct a novel framework within which to logically pursue various approaches that could afford increased selectivity in steroid-based therapies. Published by Elsevier Ireland Ltd.
C1 [Simons, S. Stoney, Jr.] NIDDK, Steroid Hormones Sect, LERB, NIH, Bethesda, MD 20892 USA.
[Kumar, Raj] Commonwealth Med Coll, Dept Basic Sci, Scranton, PA USA.
RP Simons, SS (reprint author), NIDDK, CEB, NIH, Bldg 10,Room 8N-307B, Bethesda, MD 20892 USA.
EM stoneys@helix.nih.gov; rkumar@tcmedc.org
FU NIH, The National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK)
FX We thank Yun-Bo Shi (NICHD/NIH), Dan Larson (NCI/NIH), Hans Luecke
(NIDDK/NIH), and especially James McNally (NCI/NIH) for constructive
criticism. Part of this research (SSS) was supported by the Intramural
Research Program of the NIH, The National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK).
NR 44
TC 11
Z9 11
U1 0
U2 9
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0303-7207
J9 MOL CELL ENDOCRINOL
JI Mol. Cell. Endocrinol.
PD AUG 25
PY 2013
VL 376
IS 1-2
BP 81
EP 84
DI 10.1016/j.mce.2013.06.007
PG 4
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 200TZ
UT WOS:000323095100009
PM 23792173
ER
PT J
AU Bosch, B
Berger, AC
Khandelwal, S
Heipertz, EL
Scharf, B
Santambrogio, L
Roche, PA
AF Bosch, Berta
Berger, Adam C.
Khandelwal, Sanjay
Heipertz, Erica L.
Scharf, Brian
Santambrogio, Laura
Roche, Paul A.
TI Disruption of Multivesicular Body Vesicles Does Not Affect Major
Histocompatibility Complex (MHC) Class II-Peptide Complex Formation and
Antigen Presentation by Dendritic Cells
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID CHOLESTEROL HOMEOSTASIS; COMPARTMENTS; TRANSPORT; DISEASE; TRAFFICKING;
MOLECULES; CLATHRIN; PATHWAY; BODIES; GENE
AB The antigen processing compartments in antigen-presenting cells (APCs) have well known characteristics of multivesicular bodies (MVBs). However, the importance of MVB integrity to APC function remains unknown. In this study, we have altered the ultrastructure of the MVB by perturbing cholesterol content genetically through the use of a deletion of the lipid transporter Niemann-Pick type C1 (NPC1). Immunofluorescence and electron microscopic analyses reveal that the antigen processing compartments in NPC1(-/-) dendritic cells (DCs) have an abnormal ultrastructure in that the organelles are enlarged and the intraluminal vesicles are almost completely absent and those remaining are completely disorganized. MHC-II is restricted to the limiting membrane of these enlarged MVBs where it colocalizes with the peptide editor H2-DM. Curiously, proteolytic removal of the chaperone protein Invariant chain from MHC-II, degradation of internalized foreign antigens, and antigenic-peptide binding to nascent MHC-II are normal in NPC1(-/-) DCs. Antigen-pulsed NPC1(-/-) DCs are able to effectively activate antigen-specific CD4 T cells in vitro, and immunization of NPC1(-/-) mice reveals surprisingly normal CD4 T cell activation in vivo. Our data thus reveal that the localization of MHC-II on the intraluminal vesicles of multivesicular antigen processing compartments is not required for efficient antigen presentation by DCs.
C1 [Bosch, Berta; Berger, Adam C.; Khandelwal, Sanjay; Heipertz, Erica L.; Roche, Paul A.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Scharf, Brian; Santambrogio, Laura] Albert Einstein Coll Med, Dept Pathol Microbiol & Immunol, Bronx, NY 10461 USA.
RP Roche, PA (reprint author), NIH, Bldg 10,Rm 4B36, Bethesda, MD 20892 USA.
EM paul.roche@nih.gov
FU Intramural Research Program of the 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 (to P. A. R.).
NR 25
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Z9 5
U1 0
U2 2
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 23
PY 2013
VL 288
IS 34
BP 24286
EP 24292
DI 10.1074/jbc.M113.461996
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 302NW
UT WOS:000330612300001
PM 23846690
ER
PT J
AU Belzil, C
Neumayer, G
Vassilev, AP
Yap, KL
Konishi, H
Rivest, S
Sanada, K
Ikura, M
Nakatani, Y
Nguyen, MD
AF Belzil, Camille
Neumayer, Gernot
Vassilev, Alex P.
Yap, Kyoko L.
Konishi, Hiroaki
Rivest, Serge
Sanada, Kamon
Ikura, Mitsuhiko
Nakatani, Yoshihiro
Minh Dang Nguyen
TI A Ca2+-dependent Mechanism of Neuronal Survival Mediated by the
Microtubule-associated Protein p600
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID ENDOPLASMIC-RETICULUM STRESS; METHYL-D-ASPARTATE; KINASE-II CLUSTERS;
ALZHEIMERS-DISEASE; NEURODEGENERATIVE DISEASES; CEREBRAL-ISCHEMIA;
INDUCED APOPTOSIS; CNS NEURONS; CALCIUM; CALMODULIN
AB In acute and chronic neurodegeneration, Ca2+ mishandling and disruption of the cytoskeleton compromise neuronal integrity, yet abnormalities in the signaling roles of cytoskeletal proteins remain largely unexplored. We now report that the microtubule-associated protein p600 (also known as UBR4) promotes neuronal survival. Following depletion of p600, glutamate-induced Ca2+ influx through NMDA receptors, but not AMPA receptors, initiates a degenerative process characterized by endoplasmic reticulum fragmentation and endoplasmic reticulum Ca2+ release via inositol 1,4,5-trisphosphate receptors. Downstream of NMDA receptors, p600 associates with the calmodulin-calmodulin-dependent protein kinase II alpha complex. A direct and atypical p600/calmodulin interaction is required for neuronal survival. Thus, p600 counteracts specific Ca2+-induced death pathways through regulation of Ca2+ homeostasis and signaling.
C1 [Belzil, Camille; Neumayer, Gernot; Minh Dang Nguyen] Univ Calgary, Hotchkiss Brain Inst, Calgary, AB T2N 4N1, Canada.
[Belzil, Camille; Neumayer, Gernot; Minh Dang Nguyen] Univ Calgary, Dept Clin Neurosci, Calgary, AB T2N 4N1, Canada.
[Belzil, Camille; Neumayer, Gernot; Minh Dang Nguyen] Univ Calgary, Dept Cell Biol & Anat, Calgary, AB T2N 4N1, Canada.
[Belzil, Camille; Neumayer, Gernot; Minh Dang Nguyen] Univ Calgary, Dept Biochem & Mol Biol, Calgary, AB T2N 4N1, Canada.
[Vassilev, Alex P.] NICHD, NIH, Bethesda, MD 20892 USA.
[Yap, Kyoko L.; Ikura, Mitsuhiko] Univ Toronto, Ontario Canc Inst, Toronto, ON M5G 1L7, Canada.
[Konishi, Hiroaki] Prefectural Univ Hiroshima, Fac Life & Environm Sci, Shobara, Hiroshima 7270023, Japan.
[Rivest, Serge] Univ Laval, Ctr Hosp Univ Laval, Ctr Rech, Quebec City, PQ G1V 0A6, Canada.
[Sanada, Kamon] Univ Tokyo, Grad Sch Sci, Mol Genet Res Lab, Bunkyo Ku, Tokyo 1130033, Japan.
[Nakatani, Yoshihiro] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Nguyen, MD (reprint author), Univ Calgary, Hotchkiss Brain Inst, Dept Clin Neurosci, HMRB 151,3330 Hosp Dr NW, Calgary, AB T2N 4N1, Canada.
EM mdnguyen@ucalgary.ca
RI SANADA, YOSHIKADO/G-5014-2014
FU Canadian Institutes of Health Research (CIHR); Human Frontier Science
Program Organization (HFSPO); Brenda Strafford Chair Foundation in
Alzheimer's disease; Alberta Innovates Health Solutions (AIHS); Ted
Fong/Hotchkiss Brain Institute; Austrian Academy of Sciences at the
University of Calgary; Achievers in Medical Sciences award; CIHR;
Canadian Cancer Society; AIHS
FX This work was authored, in whole or in part, by National Institutes of
Health staff. This work was supported by an operating grant from the
Canadian Institutes of Health Research (CIHR), the Human Frontier
Science Program Organization (HFSPO), and the Brenda Strafford Chair
Foundation in Alzheimer's disease (to M. D. N.).; Recipient of an
Alberta Innovates Health Solutions (AIHS) studentship and a Ted
Fong/Hotchkiss Brain Institute doctoral scholarship.; Recipient of a
doctoral fellowship of the Austrian Academy of Sciences at the
University of Calgary and an Achievers in Medical Sciences award.;
Supported by CIHR and the Canadian Cancer Society and holder of a Canada
Research Chair.; Recipient of a New Investigator Award from the CIHR and
a Scholarship from AIHS.
NR 53
TC 6
Z9 6
U1 0
U2 1
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 23
PY 2013
VL 288
IS 34
BP 24452
EP 24464
DI 10.1074/jbc.M113.483107
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 302NW
UT WOS:000330612300015
PM 23861403
ER
PT J
AU Thomas, AG
Rojas, C
Tanega, C
Shen, M
Simeonov, A
Boxer, MB
Auld, DS
Ferraris, DV
Tsukamoto, T
Slusher, BS
AF Thomas, Ajit G.
Rojas, Camilo
Tanega, Cordelle
Shen, Min
Simeonov, Anton
Boxer, Matthew B.
Auld, Douglas S.
Ferraris, Dana V.
Tsukamoto, Takashi
Slusher, Barbara S.
TI Kinetic characterization of ebselen, chelerythrine and apomorphine as
glutaminase inhibitors
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Cancer; HIV-associated dementia (HAD); Glutamate; Glutamine;
Glutaminase; Kinetics
ID KIDNEY-TYPE GLUTAMINASE; BLIND CLINICAL-TRIAL; PHASE-I;
6-DIAZO-5-OXO-L-NORLEUCINE DON; GLUTAMATE PRODUCTION; METABOLISM;
CANCER; CELLS; ANTIOXIDANT; SANGUINARINE
AB Glutaminase catalyzes the hydrolysis of glutamine to glutamate and plays a central role in the proliferation of neoplastic cells via glutaminolysis, as well as in the generation Of excitotoxic glutamate in central nervous system disorders such as HIV-associated dementia (HAD) and multiple sclerosis. Both glutaminase siRNA and glutaminase inhibition have been shown to be effective in in vitro models of cancer and HAD, suggesting a potential role for small molecule glutaminase inhibitors. However, there are no potent, selective inhibitors of glutaminase currently available. The two prototypical glutaminase inhibitors, BPTES and DON, are either insoluble or non-specific. In a search for more drug-like glutaminase inhibitors, we conducted a screen of 1280 in vivo active drugs (Library of Pharmacologically Active Compounds (LOPAC(1280))) and identified ebselen, chelerythrine and (R)-apomorphine. The newly identified inhibitors exhibited 10 to 1500-fold greater affinities than DON and BPTES and over 100-fold increased efficiency of inhibition. Although non-selective, it is noteworthy that the affinity of ebselen for glutaminase is more potent than any other activity yet described. It is possible that the previously reported biological activity seen with these compounds is due, in part, to glutaminase inhibition. Ebselen, chelerythrine and apomorphine complement the armamentarium of compounds to explore the role of glutaminase in disease. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Thomas, Ajit G.; Rojas, Camilo; Ferraris, Dana V.; Tsukamoto, Takashi; Slusher, Barbara S.] Johns Hopkins Univ, Sch Med, Brain Sci Inst, Baltimore, MD 21205 USA.
[Tanega, Cordelle; Shen, Min; Simeonov, Anton; Boxer, Matthew B.; Auld, Douglas S.] NIH, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA.
[Tsukamoto, Takashi; Slusher, Barbara S.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
[Slusher, Barbara S.] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA.
RP Slusher, BS (reprint author), Johns Hopkins Univ, Sch Med, Brain Sci Inst, JGR Bldg,Suite 277,855 N Wolfe St, Baltimore, MD 21205 USA.
EM bslusher@jhmi.edu
FU Johns Hopkins Brain Science Institute; NIH [1-R03-MH093170-01A1,
1R21NS074151-01]
FX This work was supported in part by the Johns Hopkins Brain Science
Institute, and NIH Grants 1-R03-MH093170-01A1 (to BSS) and
1R21NS074151-01 (to TT).
NR 45
TC 12
Z9 12
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 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD AUG 23
PY 2013
VL 438
IS 2
BP 243
EP 248
DI 10.1016/j.bbrc.2013.06.110
PG 6
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 211NT
UT WOS:000323915700001
PM 23850693
ER
PT J
AU Oliveira, MJA
van Deventer, HE
Bachmann, LM
Warnick, GR
Nakajima, K
Nakamura, M
Sakurabayashi, I
Kimberly, MM
Shamburek, RD
Korzun, WJ
Myers, GL
Miller, WG
Remaley, AT
AF Oliveira, Marcelo Jose Andrade
van Deventer, Hendrick E.
Bachmann, Lorin M.
Warnick, G. Russell
Nakajima, Katsuyuki
Nakamura, Masakasu
Sakurabayashi, Ikunosuke
Kimberly, Mary M.
Shamburek, Robert D.
Korzun, William J.
Myers, Gary L.
Miller, W. Greg
Remaley, Alan T.
TI Evaluation of four different equations for calculating LDL-C with eight
different direct HDL-C assays
SO CLINICA CHIMICA ACTA
LA English
DT Article
DE Cholesterol; Cardiovascular disease; Low-density lipoproteins;
Friedewald equation
ID DENSITY-LIPOPROTEIN CHOLESTEROL; CORONARY-HEART-DISEASE; RISK;
POPULATION; FORMULA; PLASMA; ULTRACENTRIFUGATION; CLASSIFICATION;
ACCURACY; VALUES
AB Background: Low-density lipoprotein cholesterol (LDL-C) is often calculated (cLDL-C) by the Friedewald equation, which requires high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG). Because there have been considerable changes in the measurement of HDL-C with the introduction of direct assays, several alternative equations have recently been proposed.
Methods: We compared 4 equations (Friedewald, Vujovic, Chen, and Anandaraja) for cLDL-C, using 8 different direct HDL-C (dHDL-C) methods. LDL-C values were calculated by the 4 equations and determined by the 13 quantification reference method procedure in 164 subjects.
Results: For normotriglyceridemic samples (TG < 200 mg/dl), between 6.2% and 24.8% of all results exceeded the total error goal of 12% for LDL-C, depending on the dHDL-C assay and cLDL-C equation used. Friedewald equation was found to be the optimum equation for most but not all dHDL-C assays, typically leading to less than 10% misclassification of cardiovascular risk based on LDL-C. Hypertriglyceridemic samples (>= 200 mg/dl) showed a large cardiovascular risk misclassification rate (30%-50%) for all combinations of dHDL-C assays and cLDL-C equations.
Conclusion: The Friedewald equation showed the best performance for estimating LDL-C, but its accuracy varied considerably depending on the specific dHDL-C assay used. None of the cLDL-C equations performed adequately for hypertriglyceridemic samples. Published by Elsevier B.V.
C1 [Oliveira, Marcelo Jose Andrade; Shamburek, Robert D.; Remaley, Alan T.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
[van Deventer, Hendrick E.] Lancet Labs, ZA-0043 Pretoria, South Africa.
[Bachmann, Lorin M.; Korzun, William J.; Miller, W. Greg] Virginia Commonwealth Univ, Dept Pathol, Richmond, VA 23284 USA.
[Warnick, G. Russell] Hlth Diagnost Lab, Richmond, VA 23219 USA.
[Nakajima, Katsuyuki] Nakajima & Associates Co, Maebashi, Guma 3710805, Japan.
[Nakamura, Masakasu] Osaka Med Ctr Hlth Sci & Promot, Dept Hlth Promot & Educ, Higashinari Ku, Osaka 5370025, Japan.
[Sakurabayashi, Ikunosuke] Jichi Med Univ, Shimotsuke, Tochigi, Japan.
[Myers, Gary L.] Amer Assoc Clin Chem, Washington, DC USA.
RP Remaley, AT (reprint author), NIH, Dept Lab Med, Ctr Clin, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM aremaley1@mail.nih.gov
FU Warren Grant Magnuson Clinical Center; Intramural Research Program of
the National Institutes of Health; Denka Seiken; Kyowa Medex; Sekisui
Medical; Serotec; Sysmex International Reagents; UMA; Wako Pure Chemical
Industries; Genzyme; Pacific Biometrics Research Foundation
FX M. J. Oliveira, A. T. Remaley, and H. E. van Deventer were supported by
the Warren Grant Magnuson Clinical Center, Intramural Research Program
of the National Institutes of Health. G. Miller was supported by the
Denka Seiken, Kyowa Medex, Sekisui Medical, Serotec, Sysmex
International Reagents, UMA and Wako Pure Chemical Industries, who
donated reagents, calibrators, and controls and contributed financial
support to Pacific Biometrics Research Foundation. Genzyme and Pointe
Scientific contributed financial support to Pacific Biometrics Research
Foundation. Pacific Biometrics Research Foundation provided a grant to
Virginia Commonwealth University (funded by the financial contributions
noted above). Roche Diagnostics donated reagents, calibrators, controls,
and a Hitachi 917 instrument
NR 21
TC 12
Z9 12
U1 2
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0009-8981
J9 CLIN CHIM ACTA
JI Clin. Chim. Acta
PD AUG 23
PY 2013
VL 423
BP 135
EP 140
DI 10.1016/j.cca.2013.04.009
PG 6
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 172BY
UT WOS:000320976100025
PM 23628525
ER
PT J
AU Laurence, A
Belkaid, Y
O'Shea, JJ
AF Laurence, Arian
Belkaid, Yasmine
O'Shea, John J.
TI A Degrading View of Regulatory T Cells
SO IMMUNITY
LA English
DT Editorial Material
ID IN-VIVO; PLASTICITY; STABILITY
AB Studies by van Loosdregt et al. and Chen et al. in this issue of Immunity provide evidence for previously unrecognized players that regulate FOXP3 degradation. These are interesting developments that point to unappreciated mechanisms by which inflammatory signals can impact expression of FOXP3 and possibly the stability of Treg cell phenotypes.
C1 [Laurence, Arian; Belkaid, Yasmine; O'Shea, John J.] NIAMSD, Bethesda, MD 20892 USA.
RP O'Shea, JJ (reprint author), NIAMSD, Bethesda, MD 20892 USA.
EM osheaj@arb.niams.nih.gov
RI Laurence, Arian/A-8770-2009
OI Laurence, Arian/0000-0003-0942-8292
NR 11
TC 2
Z9 4
U1 1
U2 4
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 AUG 22
PY 2013
VL 39
IS 2
BP 201
EP 203
DI 10.1016/j.immuni.2013.08.017
PG 4
WC Immunology
SC Immunology
GA AA2UE
UT WOS:000330948800002
PM 23973216
ER
PT J
AU Zhou, TQ
Zhu, J
Wu, XL
Moquin, S
Zhang, BS
Acharya, P
Georgiev, IS
Altae-Tran, HR
Chuang, GY
Joyce, MG
Do Kwon, Y
Longo, NS
Louder, MK
Luongo, T
McKee, K
Schramm, CA
Skinner, J
Yang, YP
Yang, ZJ
Zhang, ZH
Zheng, AQ
Bonsignori, M
Haynes, BF
Scheid, JF
Nussenzweig, MC
Simek, M
Burton, DR
Koff, WC
Mullikin, JC
Connors, M
Shapiro, L
Nabel, GJ
Mascola, JR
Kwong, PD
AF Zhou, Tongqing
Zhu, Jiang
Wu, Xueling
Moquin, Stephanie
Zhang, Baoshan
Acharya, Priyamvada
Georgiev, Ivelin S.
Altae-Tran, Han R.
Chuang, Gwo-Yu
Joyce, M. Gordon
Do Kwon, Young
Longo, Nancy S.
Louder, Mark K.
Luongo, Timothy
McKee, Krisha
Schramm, Chaim A.
Skinner, Jeff
Yang, Yongping
Yang, Zhongjia
Zhang, Zhenhai
Zheng, Anqi
Bonsignori, Mattia
Haynes, Barton F.
Scheid, Johannes F.
Nussenzweig, Michel C.
Simek, Melissa
Burton, Dennis R.
Koff, Wayne C.
Mullikin, James C.
Connors, Mark
Shapiro, Lawrence
Nabel, Gary J.
Mascola, John R.
Kwong, Peter D.
CA NISC Comparative Sequencing Progra
TI Multidonor Analysis Reveals Structural Elements, Genetic Determinants,
and Maturation Pathway for HIV-1 Neutralization by VRC01-Class
Antibodies
SO IMMUNITY
LA English
DT Article
ID B-CELL RECEPTORS; CD4-BINDING SITE; VACCINE EFFICACY; FOUNDER VIRUS;
BINDING-SITE; BROAD; ENVELOPE; PROTEIN; REPERTOIRE; PROTECTION
AB Antibodies of the VRC01 class neutralize HIV-1, arise in diverse HIV-1-infected donors, and are potential templates for an effective HIV-1 vaccine. However, the stochastic processes that generate repertoires in each individual of >10(12) antibodies make elicitation of specific antibodies uncertain. Here we determine the ontogeny of the VRC01 class by crystallography and next-generation sequencing. Despite antibody-sequence differences exceeding 50%, antibody-gp120 cocrystal structures reveal VRC01-class recognition to be remarkably similar. B cell transcripts indicate that VRC01-class antibodies require few specific genetic elements, suggesting that naive-B cells with VRC01-class features are generated regularly by recombination. Virtually all of these fail to mature, however, with only a few-likely one-ancestor B cell expanding to form a VRC01-class lineage in each donor. Developmental similarities in multiple donors thus reveal the generation of VRC01-class antibodies to be reproducible in principle, thereby providing a framework for attempts to elicit similar antibodies in the general population.
C1 [Zhou, Tongqing; Zhu, Jiang; Wu, Xueling; Moquin, Stephanie; Zhang, Baoshan; Acharya, Priyamvada; Georgiev, Ivelin S.; Altae-Tran, Han R.; Chuang, Gwo-Yu; Joyce, M. Gordon; Do Kwon, Young; Longo, Nancy S.; Louder, Mark K.; Luongo, Timothy; McKee, Krisha; Yang, Yongping; Yang, Zhongjia; Zheng, Anqi; Shapiro, Lawrence; Nabel, Gary J.; Mascola, John R.; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Skinner, Jeff] NIAID, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, NIH, Bethesda, MD 20892 USA.
[Connors, Mark] NIAID, Lab Immunoregulat, NIH, Bethesda, MD 20892 USA.
[Mullikin, James C.; NISC Comparative Sequencing Progra] NHGRI, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA.
[Schramm, Chaim A.; Zhang, Zhenhai; Shapiro, Lawrence] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA.
[Bonsignori, Mattia; Haynes, Barton F.] Duke Univ, Sch Med, Duke Human Vaccine Inst, Durham, NC 27710 USA.
[Bonsignori, Mattia; Haynes, Barton F.] Duke Univ, Med Ctr, Durham, NC 27710 USA.
[Scheid, Johannes F.; Nussenzweig, Michel C.] Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA.
[Nussenzweig, Michel C.] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 USA.
[Simek, Melissa; Koff, Wayne C.] Int AIDS Vaccine Initiat, New York, NY 10038 USA.
[Burton, Dennis R.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
[Burton, Dennis R.] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA.
[Burton, Dennis R.] Scripps Res Inst, Ctr HIV AIDS Vaccine Immunol & Immunogen Design, La Jolla, CA 92037 USA.
[Burton, Dennis R.] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02129 USA.
RP Mascola, JR (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM jmascola@nih.gov; pdkwong@nih.gov
RI Kwon, Young Do/A-6957-2010; Zhou, Tongqing/A-6880-2010;
OI Zhou, Tongqing/0000-0002-3935-4637; Skinner, Jeff/0000-0001-5697-0442
FU Intramural Research Program of the Vaccine Research Center, National
Institute of Allergy and Infectious Diseases; National Human Genome
Research Institute, National Institutes of Health; International AIDS
Vaccine Initiative's Neutralizing Antibody Consortium; Center for
HIV/AIDS Vaccine Immunology Grant from the National Institutes from
Health [AI 5U19 AI 067854-06]; US Department of Energy, Basic Energy
Sciences, Office of Science [W-31-109-Eng-38]
FX We thank H. Coleman, M. Park, B. Schmidt, and A. Young for 454
pyrosequencing at the NIH Intramural Sequencing Center (NISC), J.
Stuckey for assistance with figures, and the study participants and
research staff at each of the Protocol G clinical centers, the Protocol
G team members, the IAVI Human Immunology Laboratory and the Protocol G
clinical investigators, including George Miiro, Anton Pozniak, Dale
McPhee, Olivier Manigart, Etienne Karita, Andre Inwoley, Walter Jaoko,
Jack DeHovitz, Linda-Gail Bekker, Punnee Pitisuttithum, Robert Paris,
Jennifer Serwanga, and Susan Allen. We also thank Anthony West and
members of the Structural Biology Section and Structural Bioinformatics
Core, Vaccine Research Center, for discussions or comments on the
manuscript. Support for this work was provided by the Intramural
Research Program of the Vaccine Research Center, National Institute of
Allergy and Infectious Diseases and the National Human Genome Research
Institute, National Institutes of Health, and by grants from the
International AIDS Vaccine Initiative's Neutralizing Antibody Consortium
and by the Center for HIV/AIDS Vaccine Immunology Grant AI 5U19 AI
067854-06 from the National Institutes from Health. Use of sector 22
(Southeast Region Collaborative Access team) at the Advanced Photon
Source was supported by the US Department of Energy, Basic Energy
Sciences, Office of Science, under contract number W-31-109-Eng-38.
NR 34
TC 101
Z9 102
U1 0
U2 20
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 AUG 22
PY 2013
VL 39
IS 2
BP 245
EP 258
DI 10.1016/j.immuni.2013.04.012
PG 14
WC Immunology
SC Immunology
GA AA2UE
UT WOS:000330948800008
PM 23911655
ER
PT J
AU Ouyang, WM
Oh, SA
Ma, Q
Bivona, MR
Zhu, JF
Li, MO
AF Ouyang, Weiming
Oh, Soyoung A.
Ma, Qian
Bivona, Michael R.
Zhu, Jinfang
Li, Ming O.
TI TGF-beta Cytokine Signaling Promotes CD8(+) T Cell Development and
Low-Affinity CD4(+) T Cell Homeostasis by Regulation of Interleukin-7
Receptor alpha Expression
SO IMMUNITY
LA English
DT Article
ID ROR-GAMMA-T; NEGATIVE SELECTION; IN-VIVO; DIFFERENTIATION; NAIVE;
TRANSCRIPTION; MECHANISMS; SURVIVAL; IL-7; PROLIFERATION
AB Interleukin-7 receptor alpha chain (IL-7R alpha) is induced upon T cell positive selection and controls thymic CD8-lineage specification and peripheral naive T cell homeostasis. How IL-7R alpha expression is regulated in developing thymocytes is unclear. Here, we show that transforming growth factor beta (TGF-beta) signaling promoted IL-7R alpha expression and CD8(+) T cell differentiation. In addition, TGF-beta signaling was required for high IL-7R alpha expression in CD4(+) T cells bearing low-affinity T cell receptors, and the abrogation of TGF-beta receptor expression led to failed maintenance of peripheral CD4(+) T cells. Compromised IL-7R alpha expression in TGF-beta-receptor-deficient T cells was associated with increased expression of the Il7ra transcriptional repressor, Gfi-1. IL-7R alpha transgenesis or T-cell-specific ablation of Gfi-1 restored IL-7R alpha expression and largely ameliorated the development and homeostasis defects of TGF-beta-receptor-deficient T cells. These findings reveal functions for TGF-beta signaling in controlling IL-7R alpha expression and in promoting T cell repertoire diversification.
C1 [Ouyang, Weiming; Oh, Soyoung A.; Ma, Qian; Bivona, Michael R.; Li, Ming O.] Mem Sloan Kettering Canc Ctr, Program Immunol, New York, NY 10065 USA.
[Zhu, Jinfang] NIAID, Immunol Lab, Bethesda, MD 20892 USA.
RP Li, MO (reprint author), Mem Sloan Kettering Canc Ctr, Program Immunol, New York, NY 10065 USA.
EM lim@mskcc.org
RI Zhu, Jinfang/B-7574-2012
FU National Institute of Arthritis, Musculoskeletal, and Skin Diseases [RO1
AR060723]; Division of Intramural Research, National Institute of
Allergy and Infectious Diseases, National Institutes of Health, USA;
[T32-CA9149-35]
FX We thank K. Bottomly for providing AND mice, and A. Singer for providing
IL-7R transgenic mice. The projects described were supported by grants
from the National Institute of Arthritis, Musculoskeletal, and Skin
Diseases (RO1 AR060723 to M.O.L.). J.Z. is supported by the Division of
Intramural Research, National Institute of Allergy and Infectious
Diseases, National Institutes of Health, USA. S.A.O. is supported by
T32-CA9149-35.
NR 38
TC 9
Z9 11
U1 3
U2 7
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 AUG 22
PY 2013
VL 39
IS 2
BP 335
EP 346
DI 10.1016/j.immuni.2013.07.016
PG 12
WC Immunology
SC Immunology
GA AA2UE
UT WOS:000330948800015
PM 23932572
ER
PT J
AU Nguyen, JB
Pool, CD
Wong, CYB
Treger, RS
Williams, DL
Cappello, M
Lea, WA
Simeonov, A
Vermeire, JJ
Modis, Y
AF Nguyen, Jennifer B.
Pool, Christopher D.
Wong, Christina Y. B.
Treger, Rebecca S.
Williams, David L.
Cappello, Michael
Lea, Wendy A.
Simeonov, Anton
Vermeire, Jon J.
Modis, Yorgo
TI Peroxiredoxin-1 from the Human Hookworm Ancylostoma ceylanicum Forms a
Stable Oxidized Decamer and Is Covalently Inhibited by Conoidin A
SO CHEMISTRY & BIOLOGY
LA English
DT Article
ID ENDOPLASMIC-RETICULUM; CRYSTAL-STRUCTURE; 2-CYS PEROXIREDOXIN; HELMINTH
INFECTIONS; IV; PEROXIDASE; REFINEMENT; MECHANISMS; CHEMISTRY; PARASITES
AB Hookworms are parasitic nematodes that have a devastating impact on global health, particularly in developing countries. We report a biochemical and structural analysis of a peroxiredoxin from the hookworm Ancylostoma ceylanicum, AcePrx-1. Peroxiredoxins provide antioxidant protection and act as signaling molecules and chaperones. AcePrx-1 is expressed in adult hookworms and can be inactivated by 2,3-bis(bromomethyl)quinoxaline-1,4-dioxide (conoidin A). Conoidin A inactivates AcePrx-1 by alkylating or crosslinking the catalytic cysteines, while maintaining the enzyme in the "locally unfolded" conformation. Irreversible oxidation of the resolving cysteine may contribute additional inhibitory activity. A crystal structure of oxidized AcePrx-1 reveals a disulfide-linked decamer. A helix macrodipole near the active site increases the reactivity of the catalytic cysteines to conoidin A. This work demonstrates the promise of conoidin compounds as probes to evaluate peroxiredoxins as drug targets in human parasites.
C1 [Nguyen, Jennifer B.; Modis, Yorgo] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA.
[Pool, Christopher D.; Wong, Christina Y. B.; Treger, Rebecca S.; Cappello, Michael; Vermeire, Jon J.] Yale Univ, Sch Med, Program Int Child Hlth, Child Hlth Res Ctr, New Haven, CT 06520 USA.
[Pool, Christopher D.; Wong, Christina Y. B.; Treger, Rebecca S.; Cappello, Michael; Vermeire, Jon J.] Yale Univ, Sch Med, Dept Pediat, Child Hlth Res Ctr, New Haven, CT 06520 USA.
[Williams, David L.] Rush Univ, Med Ctr, Dept Immunol Microbiol, Chicago, IL 60612 USA.
[Lea, Wendy A.; Simeonov, Anton] NHGRI, NIH Chem Genom Ctr, NIH, Bethesda, MD 20892 USA.
RP Modis, Y (reprint author), Yale Univ, Dept Mol Biophys & Biochem, POB 6666, New Haven, CT 06520 USA.
EM yorgo.modis@yale.edu
OI Modis, Yorgo/0000-0002-6084-0429
FU Burroughs Wellcome Investigator Award; NIH [P01 GM022778, K22 AI08476,
T32 GM08283]; Office of Biological of the US Department of Energy;
Office of Basic Energy Sciences of the US Department of Energy
FX We thank staff at beamline 24-ID-E of the Northeastern Collaborative
Access Team at the Advanced Photon Source of the Argonne National
Laboratory, and at the X25 and X29A beamlines of the National
Synchrotron Light Source at Brookhaven National Laboratory. We thank
Lisa Harrison for a critical reading of the manuscript. We acknowledge
Alanna Schepartz for use of her mass spectrometer and Tae Han Kim for
advice on chemical mechanisms. This work was supported by a Burroughs
Wellcome Investigator Award and NIH grant P01 GM022778 (to Y.M.), and
NIH grant K22 AI08476 (to J.J.V.). NIH training grant T32 GM08283
provided partial support (to J.B.N.). Use of the APS and NSLS is
supported by the Offices of Biological and of Basic Energy Sciences of
the US Department of Energy.
NR 42
TC 5
Z9 5
U1 0
U2 10
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-5521
EI 1879-1301
J9 CHEM BIOL
JI Chem. Biol.
PD AUG 22
PY 2013
VL 20
IS 8
BP 991
EP 1001
DI 10.1016/j.chembiol.2013.06.011
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 297RB
UT WOS:000330271500005
PM 23891152
ER
PT J
AU Mehta, NN
Li, K
Szapary, P
Krueger, J
Brodmerkel, C
AF Mehta, Nehal N.
Li, Katherine
Szapary, Philippe
Krueger, James
Brodmerkel, Carrie
TI Modulation of cardiometabolic pathways in skin and serum from patients
with psoriasis
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Article
DE Inflammation; Atherosclerosis; Lipid metabolism; Psoriasis
ID TO-SEVERE PSORIASIS; ATHEROSCLEROSIS; INFLAMMATION; MODERATE; DISEASE;
RISK; MECHANISMS; MORTALITY; COHORT
AB Background: Moderate-to-severe psoriasis is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD); however, the link is poorly understood.
Methods: Skin and serum from patients with psoriasis were evaluated to understand if there was evidence of dysregulation in a targeted group of inflammatory and lipid genes related to ASCVD. Microarray analyses of expression of targeted ASCVD genes from skin in 89 patients with moderate-to-severe psoriasis from the ACCEPT trial were compared with non-diseased skin from healthy controls (n = 25). Serum (n = 149) was tested at baseline for monocyte chemoattractant protein-1 (MCP-1), macrophage-derived chemokine (MDC), and apolipoprotein-A1 (Apo-A1) comparing to healthy controls (n=162).
Results: An increase in skin gene expression for MCP-1 (7.98-fold) and MDC (6.66-fold) (p < 0.001 each) was observed in lesional versus healthy skin. Significant decreases in liver X receptor-alpha (LXR-alpha) (-5.94-fold), a protective lipoprotein metabolism gene, and in peroxisome proliferator-activated receptor-alpha (PPAR-alpha) (-7.58-fold), a protective anti-inflammatory and lipid modulating gene, were observed in lesional versus healthy skin (p < 0.001 each). Serum analyses revealed that MCP-1 (502 vs. 141 pg/mL) and MDC (1240 vs. 409 pg/mL) levels were significantly elevated in psoriasis compared with healthy controls (p < 0.001 each). Dysregulated lipid metabolism was also evident in the serum, as Apo-A1, a protein product related to PPAR-alpha activation, was significantly decreased in patients with psoriasis compared with healthy controls (25.2 vs. 38.9 mg/dL; p < 0.001).
Conclusions: Analyses of targeted genes and their products known to be associated with ASCVD revealed dysregulation of inflammatory (MCP-1 and MDC) and lipid metabolism (LXR-alpha, PPAR-alpha) genes in psoriasis. These findings provide evidence of a potential shared pathophysiology linking psoriasis to cardiometabolic diseases.
C1 [Mehta, Nehal N.] NHLBI, Sect Inflammat & Cardiometab Dis, Bethesda, MD 20892 USA.
[Li, Katherine; Szapary, Philippe; Brodmerkel, Carrie] Janssen Res & Dev LLC, Spring House, PA USA.
[Krueger, James] Rockefeller Univ, New York, NY 10021 USA.
RP Mehta, NN (reprint author), NHLBI, Sect Inflammat & Cardiometab Dis, Bldg 10, Bethesda, MD 20892 USA.
EM nehal.mehta@nih.gov
FU Janssen Research & Development, LLC; Rockefeller Institute from Janssen
FX This study was funded by Janssen Research & Development, LLC. N. Mehta
has no conflicts of interest. K. Li, P. Szapary, and C. Brodmerkel are
employees of Janssen Research & Development, LLC, and own stock in
Johnson & Johnson, of which Janssen is a subsidiary. J. Krueger has
received research grants on behalf of Rockefeller Institute from Janssen
(formerly Centocor), honoraria from Janssen (Centocor), and has served
as a consultant/advisory board member for Janssen (Centocor) and Amgen.
NR 23
TC 13
Z9 13
U1 1
U2 5
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 AUG 22
PY 2013
VL 11
AR 194
DI 10.1186/1479-5876-11-194
PG 8
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 209LN
UT WOS:000323758500001
PM 23965158
ER
PT J
AU Abate-Daga, D
Hanada, K
Davis, JL
Yang, JC
Rosenberg, SA
Morgan, RA
AF Abate-Daga, Daniel
Hanada, Ken-ichi
Davis, Jeremy L.
Yang, James C.
Rosenberg, Steven A.
Morgan, Richard A.
TI Expression profiling of TCR-engineered T cells demonstrates
overexpression of multiple inhibitory receptors in persisting
lymphocytes
SO BLOOD
LA English
DT Article
ID HERPESVIRUS ENTRY MEDIATOR; CANCER REGRESSION; TRANSFER IMMUNOTHERAPY;
MELANOMA PATIENTS; GENE-THERAPY; SOLID TUMORS; EXHAUSTION; MOLECULES;
ANTIGEN; SAFETY
AB Despite significant progress in the development of adoptive cell-transfer therapies (ACTs) using gene-engineered T cells, little is known about the fate of cells following infusion. To address that, we performed a comparative analysis of gene expression between T-cell receptor-engineered lymphocytes persisting in the circulation 1 month after administration and the product that was infused. We observed that 156 genes related to immune function were differentially expressed, including underexpression of stimulators of lymphocyte function and overexpression of inhibitory genes in postinfusion cells. Of genes overexpressed postinfusion, the product of programmed cell death 1 (PDCD1), coinhibitory receptor PD-1, was expressed at a higher percentage in postinfusion lymphocytes than in the infusion product. This was associated with a higher sensitivity to inhibition of cytokine production by interaction with its ligand PD-L1. Coinhibitory receptor CD160 was also overexpressed in persisting cells, and its expression was associated with decreased reactivity, which surprisingly was found to be ligand-independent. These results contribute to a deeper understanding of the properties of transgenic lymphocytes used to treat human malignancies and may provide a rationale for the development of combination therapies as a method to improve ACT. This trial was registered at www.clinicaltrials.gov as #NCT00509288, #NCT00923195, and #NCT01273181.
C1 [Abate-Daga, Daniel; Hanada, Ken-ichi; Davis, Jeremy L.; Yang, James C.; Rosenberg, Steven A.; Morgan, Richard A.] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Morgan, RA (reprint author), NCI, Surg Branch, CRC, Bldg 10,Room 3W-5940,10 Ctr Dr, Bethesda, MD 20892 USA.
EM rmorgan@mail.nih.gov
RI Hanada, Ken-ichi/L-2481-2013
OI Hanada, Ken-ichi/0000-0003-2959-1257
FU National Cancer Institute, Center for Cancer Research, National
Institutes of Health (Bethesda, MD)
FX This work was supported by the intramural program of the National Cancer
Institute, Center for Cancer Research, National Institutes of Health
(Bethesda, MD).
NR 49
TC 23
Z9 24
U1 0
U2 9
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD AUG 22
PY 2013
VL 122
IS 8
BP 1399
EP 1410
DI 10.1182/blood-2013-04-495531
PG 12
WC Hematology
SC Hematology
GA 204UD
UT WOS:000323394300017
PM 23861247
ER
PT J
AU Chun, JH
Telu, S
Lu, SY
Pike, VW
AF Chun, Joong-Hyun
Telu, Sanjay
Lu, Shuiyu
Pike, Victor W.
TI Radiofluorination of diaryliodonium tosylates under aqueous-organic and
cryptand-free conditions
SO ORGANIC & BIOMOLECULAR CHEMISTRY
LA English
DT Article
ID POSITRON-EMISSION-TOMOGRAPHY; DRUG DEVELOPMENT; SALTS; FLUORIDATION;
PET; SELECTIVITY; REACTIVITY; SOLVATION; CHEMISTRY; HYDRATION
AB Positron emission tomography (PET) has growing importance as a molecular imaging technique in clinical research and drug development. Methods for producing PET radiotracers utilizing cyclotron-produced [F-18]fluoride ion (t(1/2) = 109.7 min) without the need for complete removal of irradiated target [O-18]-water and addition of cryptand are keenly sought for practical convenience and efficiency. Several structurally diverse diaryliodonium tosylates, XArl(+)Ar'Y TsO- (X = H or p-MeO), were investigated in a microfluidic apparatus for their reactivity towards radiofluorination with high specific activity (no-carrier-added) [F-18]fluoride ion in mixtures of DMF and irradiated target [O-18]water in the absence of cryptand. Salts bearing a para or ortho electron-withdrawing group Y (e.g., Y = p-CN) reacted rapidly (similar to 3 min) to give the expected major [F-18]fluoroarene product, [F-18]FArY, in useful moderate radiochemical yields even when the solvent had an [O-18]water content up to 28%. Salts bearing electron-withdrawing groups in meta position (e.g., Y = m-NO2), or an electron-donating substituent (Y = p-OMe), gave low radiochemical yields under the same conditions.
C1 [Chun, Joong-Hyun; Telu, Sanjay; Lu, Shuiyu; Pike, Victor W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
RP Lu, SY (reprint author), NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
EM Shuiyu.Lu@mail.nih.gov
OI Lu, Shuiyu/0000-0003-0310-4318
FU Intramural Research Program of the National Institutes of Health (NIMH)
FX This research was supported by the Intramural Research Program of the
National Institutes of Health (NIMH). The authors are grateful to the
NIH Clinical Center PET Department (Chief, Dr Peter Herscovitch) for the
cyclotron production of fluorine-18.
NR 40
TC 22
Z9 22
U1 1
U2 19
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 1477-0520
EI 1477-0539
J9 ORG BIOMOL CHEM
JI Org. Biomol. Chem.
PD AUG 21
PY 2013
VL 11
IS 31
BP 5094
EP 5099
DI 10.1039/c3ob40742j
PG 6
WC Chemistry, Organic
SC Chemistry
GA 197MM
UT WOS:000322855300007
PM 23804017
ER
PT J
AU Horino, S
Uchiyama, T
So, T
Nagashima, H
Sun, S
Sato, M
Asao, A
Haji, Y
Sasahara, Y
Candotti, F
Tsuchiya, S
Kure, S
Sugamura, K
Ishii, N
AF Horino, Satoshi
Uchiyama, Toru
So, Takanori
Nagashima, Hiroyuki
Sun, Shu-lan
Sato, Miki
Asao, Atsuko
Haji, Yoichi
Sasahara, Yoji
Candotti, Fabio
Tsuchiya, Shigeru
Kure, Shigeo
Sugamura, Kazuo
Ishii, Naoto
TI Gene Therapy Model of X-linked Severe Combined Immunodeficiency Using a
Modified Foamy Virus Vector
SO PLOS ONE
LA English
DT Article
ID INTERLEUKIN-2-RECEPTOR GAMMA-CHAIN; TRANSCRIPTION START REGIONS; MOUSE
MODEL; LONG-TERM; HEMATOPOIETIC-CELLS; REPOPULATING CELLS; RETROVIRAL
VECTORS; STEM-CELLS; INTEGRATION; TRANSDUCTION
AB X-linked severe combined immunodeficiency (SCID-X1) is an inherited genetic immunodeficiency associated with mutations in the common cytokine receptor gamma chain (gamma c) gene, and characterized by a complete defect of T and natural killer (NK) cells. Gene therapy for SCID-X1 using conventional retroviral (RV) vectors carrying the gamma c gene results in the successful reconstitution of T cell immunity. However, the high incidence of vector-mediated T cell leukemia, caused by vector insertion near or within cancer-related genes has been a serious problem. In this study, we established a gene therapy model of mouse SCID-X1 using a modified foamy virus (FV) vector expressing human gamma c. Analysis of vector integration in a human T cell line demonstrated that the FV vector integration sites were significantly less likely to be located within or near transcriptional start sites than RV vector integration sites. To evaluate the therapeutic efficacy, bone marrow cells from gamma c-knockout (gamma c-KO) mice were infected with the FV vector and transplanted into gamma c-KO mice. Transplantation of the FV-treated cells resulted in the successful reconstitution of functionally active T and B cells. These data suggest that FV vectors can be effective and may be safer than conventional RV vectors for gene therapy for SCID-X1.
C1 [Horino, Satoshi; So, Takanori; Nagashima, Hiroyuki; Sun, Shu-lan; Asao, Atsuko; Haji, Yoichi; Ishii, Naoto] Tohoku Univ, Dept Microbiol & Immunol, Grad Sch Med, Sendai, Miyagi 980, Japan.
[Horino, Satoshi; Uchiyama, Toru; Sato, Miki; Haji, Yoichi; Tsuchiya, Shigeru; Kure, Shigeo] Tohoku Univ, Dept Pediat, Grad Sch Med, Sendai, Miyagi 980, Japan.
[Candotti, Fabio] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
[Sugamura, Kazuo] Miyagi Canc Ctr, Natori, Miyagi 9811293, Japan.
RP Ishii, N (reprint author), Tohoku Univ, Dept Microbiol & Immunol, Grad Sch Med, Sendai, Miyagi 980, Japan.
EM ishiin@med.tohoku.ac.jp
OI So, Takanori/0000-0003-3004-8526
FU Ministry of Education, Science, Sports and Culture of Japan [24659487,
24390118]; Japan Society for the Promotion of Science; Japan Science and
Technology Agency [111020001010004100]
FX This study was supported in part by a grant-in-aid (#24659487 and
#24390118) for scientific research on priority areas from the Ministry
of Education, Science, Sports and Culture of Japan, a grant-in-aid for
scientific research on priority areas from the Japan Society for the
Promotion of Science, and grants (#111020001010004100) from the Japan
Science and Technology Agency. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript. No additional external funding was received for this study.
NR 36
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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 AUG 21
PY 2013
VL 8
IS 8
AR e71594
DI 10.1371/journal.pone.0071594
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 218YW
UT WOS:000324470100048
PM 23990961
ER
PT J
AU Mangus, CW
Massey, PR
Fowler, DH
Amarnath, S
AF Mangus, Courtney W.
Massey, Paul R.
Fowler, Daniel H.
Amarnath, Shoba
TI Rapamycin Resistant Murine Th9 Cells Have a Stable In Vivo Phenotype and
Inhibit Graft-Versus-Host Reactivity
SO PLOS ONE
LA English
DT Article
ID EFFECTOR T-CELLS; PROMOTES; REJECTION; INFLAMMATION; INDUCTION;
AUTOPHAGY; TH1/TC1; THERAPY; DISEASE; ASTHMA
AB The cytokine micro-environment can direct murine CD4(+) T cells towards various differentiation lineages such as Th1, Th2 and Tregs even in the presence of rapamycin, which results in T cells that mediate increased in vivo effects. Recently, a new lineage of T cells known as Th9 cells that secrete increased IL-9 have been described. However, it is not known whether Th9 differentiation occurs in the presence of rapamycin or whether adoptively transferred donor Th9 cells would augment or restrict alloreactivity after experimental bone marrow transplantation. We found that CD4(+) T cells that were co-stimulated and polarized with TGF-beta and IL-4 in the presence or absence of rapamycin each yielded effector cells of Th9 phenotype that secreted increased IL-9 and expressed a transcription factor profile characteristic of both Th9 and Th2 cells (high GATA-3/low T-bet). Augmentation of T cell replete allografts with manufactured rapamycin resistant Th9 cells markedly reduced both CD4(+) and CD8(+) T cell engraftment and strongly inhibited allo-specific T cell secretion of IFN-gamma. The potency of Th9 cell inhibition of alloreactivity was similar to that of rapamycin resistant Th2 cells. Importantly, rapamycin resistant Th9 cells persisted and maintained their cytokine phenotype, thereby indicating limited differentiation plasticity of the Th9 subset. As such, Th9 differentiation proceeds in the presence of rapamycin to generate a cell therapy product that maintains high IL-9 expression in vivo while inhibiting IFN-gamma driven alloreactivity.
C1 [Mangus, Courtney W.; Massey, Paul R.; Fowler, Daniel H.; Amarnath, Shoba] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Mangus, Courtney W.] NIH, Howard Hughes Med Inst, Res Scholars Program, Chevy Chase, MD USA.
RP Amarnath, S (reprint author), NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
EM samarnath@mail.nih.gov
FU Center for Cancer Research, National Cancer Institute, Intramural
Research Program; Howard Hughes Research Scholars Program
FX This work was supported by the Center for Cancer Research, National
Cancer Institute, Intramural Research Program and by the Howard Hughes
Research Scholars Program. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 25
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PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 21
PY 2013
VL 8
IS 8
AR e72305
DI 10.1371/journal.pone.0072305
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 218YW
UT WOS:000324470100097
PM 23991087
ER
PT J
AU Ozomaro, U
Cai, GQ
Kajiwara, Y
Yoon, S
Makarov, V
Delorme, R
Betancur, C
Ruhrmann, S
Falkai, P
Grabe, HJ
Maier, W
Wagner, M
Lennertz, L
Moessner, R
Murphy, DL
Buxbaum, JD
Zuchner, S
Grice, DE
AF Ozomaro, Uzoezi
Cai, Guiqing
Kajiwara, Yuji
Yoon, Seungtai
Makarov, Vladimir
Delorme, Richard
Betancur, Catalina
Ruhrmann, Stephan
Falkai, Peter
Grabe, Hans Joergen
Maier, Wolfgang
Wagner, Michael
Lennertz, Leonhard
Moessner, Rainald
Murphy, Dennis L.
Buxbaum, Joseph D.
Zuechner, Stephan
Grice, Dorothy E.
TI Characterization of SLITRK1 Variation in Obsessive-Compulsive Disorder
SO PLOS ONE
LA English
DT Article
ID LA-TOURETTE-SYNDROME; NEURITE OUTGROWTH; ITALIAN FAMILY; ASSOCIATION;
GENE; VARIANTS; VAR321
AB Obsessive compulsive disorder (OCD) is a syndrome characterized by recurrent and intrusive thoughts and ritualistic behaviors or mental acts that a person feels compelled to perform. Twin studies, family studies, and segregation analyses provide compelling evidence that OCD has a strong genetic component. The SLITRK1 gene encodes a developmentally regulated stimulator of neurite outgrowth and previous studies have implicated rare variants in this gene in disorders in the OC spectrum, specifically Tourette syndrome (TS) and trichotillomania (TTM). The objective of the current study was to evaluate rare genetic variation in SLITRK1 in risk for OCD and to functionally characterize associated coding variants. We sequenced SLITRK1 coding exons in 381 individuals with OCD as well as in 356 control samples and identified three novel variants in seven individuals. We found that the combined mutation load in OCD relative to controls was significant (p = 0.036). We identified a missense N400I change in an individual with OCD, which was not found in more than 1000 control samples (P<0.05). In addition, we showed the the N400I variant failed to enhance neurite outgrowth in primary neuronal cultures, in contrast to wildtype SLITRK1, which enhanced neurite outgrowth in this assay. These important functional differences in the N400I variant, as compared to the wildtype SLITRK1 sequence, may contribute to OCD and OC spectrum symptoms. A synonymous L63L change identified in an individual with OCD and an additional missense change, T418S, was found in four individuals with OCD and in one individual without an OCD spectrum disorder. Examination of additional samples will help assess the role of rare SLITRK1 variation in OCD and in related psychiatric illness.
C1 [Ozomaro, Uzoezi; Zuechner, Stephan] Univ Miami, Miller Sch Med, John P Hussman Inst Human Genom, Miami, FL 33136 USA.
[Ozomaro, Uzoezi] Univ Miami, Miller Sch Med, Dept Neurosci, Miami, FL 33136 USA.
[Cai, Guiqing; Kajiwara, Yuji; Yoon, Seungtai; Makarov, Vladimir; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Dept Psychiat, Seaver Autism Ctr Res & Treatment, New York, NY USA.
[Cai, Guiqing; Kajiwara, Yuji; Yoon, Seungtai; Makarov, Vladimir; Buxbaum, Joseph D.; Grice, Dorothy E.] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY USA.
[Delorme, Richard] Hop Robert Debre, Child Psychiat Dept, F-75019 Paris, France.
[Delorme, Richard] Inst Pasteur, Paris, France.
[Betancur, Catalina] CNRS, INSERM, U952, UMR 7224, Paris, France.
[Betancur, Catalina] Univ Paris 06, Paris, France.
[Ruhrmann, Stephan] Univ Cologne, Dept Psychiat & Psychotherapy, D-50931 Cologne, Germany.
[Falkai, Peter] Univ Homburg, Dept Psychiat & Psychotherapy, Homburg, Germany.
[Grabe, Hans Joergen] Ernst Moritz Arndt Univ Greifswald, Dept Psychiat & Psychotherapy, Stralsund, Germany.
[Maier, Wolfgang; Wagner, Michael; Lennertz, Leonhard; Moessner, Rainald] Univ Bonn, Dept Psychiat & Psychotherapy, Bonn, Germany.
[Murphy, Dennis L.] NIMH, Clin Sci Lab, Intramural Res Program, Bethesda, MD 20892 USA.
[Grice, Dorothy E.] Icahn Sch Med Mt Sinai, Div Tics Obsess Compuls & Related Disorders, Dept Psychiat, New York, NY USA.
RP Grice, DE (reprint author), Icahn Sch Med Mt Sinai, Div Tics Obsess Compuls & Related Disorders, Dept Psychiat, New York, NY USA.
EM Dorothy.grice@mssm.edu
RI Wagner, Michael/E-2325-2011;
OI Wagner, Michael/0000-0003-2589-6440; Buxbaum,
Joseph/0000-0001-8898-8313; Betancur, Catalina/0000-0002-3327-4804
FU National Institutes of Health under Ruth L. Kirschstein National
Research Service Award [F31MH086275]; Lois Pope LIFE Fellowship;
Beatrice and Samuel A. Seaver Foundation; New Jersey Center for Tourette
Syndrome and Associated Disorders; National Tourette Syndrome
Association; German Research Foundation DFG [Fa 731/6]; Fondamental
Foundation, Creteil, France
FX This work was supported by the National Institutes of Health under Ruth
L. Kirschstein National Research Service Award (UO; F31MH086275), the
Lois Pope LIFE Fellowship (UO), the Beatrice and Samuel A. Seaver
Foundation (JDB), and the New Jersey Center for Tourette Syndrome and
Associated Disorders and the National Tourette Syndrome Association
(DEG), the German Research Foundation DFG (PF, MW, WM, HJG, grant Fa
731/6) and Fondamental Foundation, Creteil, France (R.D). The funders
had no role in the study design, data collection and analysis, decision
to publish, or preparation of the manuscript.
NR 25
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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 AUG 21
PY 2013
VL 8
IS 8
AR e70376
DI 10.1371/journal.pone.0070376
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 218YW
UT WOS:000324470100023
PM 23990902
ER
PT J
AU Song, XH
Lopez-Campistrous, A
Sun, L
Dower, NA
Kedei, N
Yang, J
Kelsey, JS
Lewin, NE
Esch, TE
Blumberg, PM
Stone, JC
AF Song, Xiaohua
Lopez-Campistrous, Ana
Sun, Lucy
Dower, Nancy A.
Kedei, Noemi
Yang, Jing
Kelsey, Jessica S.
Lewin, Nancy E.
Esch, Tim E.
Blumberg, Peter M.
Stone, James C.
TI RasGRPs Are Targets of the Anti-Cancer Agent Ingenol-3-Angelate
SO PLOS ONE
LA English
DT Article
ID PROTEIN-KINASE-C; NUCLEOTIDE-RELEASING PROTEIN; DIACYLGLYCEROL-BINDING
MOTIFS; PHORBOL ESTERS; SIGNALING PATHWAY; INDUCED APOPTOSIS; CELL
DEVELOPMENT; RAS ACTIVATION; B-CELLS; DELTA
AB Ingenol-3-angelate (I3A) is a non-tumor promoting phorbol ester-like compound identified in the sap of Euphoria peplus. Similar to tumor promoting phorbol esters, I3A is a diacylglycerol (DAG) analogue that binds with high affinity to the C1 domains of PKCs, recruits PKCs to cellular membranes and promotes enzyme activation. Numerous anti-cancer activities have been attributed to I3A and ascribed to I3A's effects on PKCs. We show here that I3A also binds to and activates members of the RasGRP family of Ras activators leading to robust elevation of Ras-GTP and engagement of the Raf-Mek-Erk kinase cascade. In response to I3A, recombinant proteins consisting of GFP fused separately to full-length RasGRP1 and RasGRP3 were rapidly recruited to cell membranes, consistent with direct binding of the compound to RasGRP's C1 domain. In the case of RasGRP3, IA3 treatment led to positive regulatory phosphorylation on T133 and activation of the candidate regulatory kinase PKCd. I3A treatment of select B non-Hodgkin's lymphoma cell lines resulted in quantitative and qualitative changes in Bcl-2 family member proteins and induction of apoptosis, as previously demonstrated with the DAG analogue bryostatin 1 and its synthetic analogue pico. Our results offer further insights into the anticancer properties of I3A, support the idea that RasGRPs represent potential cancer therapeutic targets along with PKC, and expand the known range of ligands for RasGRP regulation.
C1 [Song, Xiaohua; Lopez-Campistrous, Ana; Sun, Lucy; Stone, James C.] Univ Alberta, Dept Biochem, Edmonton, AB, Canada.
[Dower, Nancy A.] Univ Alberta, Dept Pediat, Edmonton, AB, Canada.
[Kedei, Noemi; Yang, Jing; Kelsey, Jessica S.; Lewin, Nancy E.; Esch, Tim E.; Blumberg, Peter M.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Stone, JC (reprint author), Univ Alberta, Dept Biochem, Edmonton, AB, Canada.
EM jim.stone@ualberta.ca
FU Canadian Institutes of Health Research (CIHR) [MOP14630]; Canadian
Cancer Society Research Institute (CCSRI) [018453]; Alberta Cancer
Foundation (ACF) [26050]; Alberta Ingenuity-Health Solutions
[200100408]; Center for Cancer Research, National Cancer Institute,
National Institutes of Health [Z1A BC 005270]
FX Research was supported by grants to JCS from the Canadian Institutes of
Health Research (CIHR grant MOP14630, http://www.cihr-irsc.gc.ca),
Canadian Cancer Society Research Institute (CCSRI grant 018453,
http://www.cancer.ca/Research.aspx), Alberta Cancer Foundation (ACF
grant 26050, http://albertacancer.ca), and Alberta Ingenuity-Health
Solutions (200100408 http://www.aihealthsolutions.ca). Research was also
supported by the Intramural Research Program of the Center for Cancer
Research, National Cancer Institute, National Institutes of Health
(Project Z1A BC 005270). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 42
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U1 0
U2 12
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 21
PY 2013
VL 8
IS 8
AR e72331
DI 10.1371/journal.pone.0072331
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 218YW
UT WOS:000324470100100
PM 23991094
ER
PT J
AU Sun, W
Park, YD
Sugui, JA
Fothergill, A
Southall, N
Shinn, P
McKew, JC
Kwon-Chung, KJ
Zheng, W
Williamson, PR
AF Sun, Wei
Park, Yoon-Dong
Sugui, Janyce A.
Fothergill, Annette
Southall, Noel
Shinn, Paul
McKew, John C.
Kwon-Chung, Kyung J.
Zheng, Wei
Williamson, Peter R.
TI Rapid Identification of Antifungal Compounds against Exserohilum
rostratum Using High Throughput Drug Repurposing Screens
SO PLOS ONE
LA English
DT Article
ID CONTAMINATED METHYLPREDNISOLONE; SERINE PALMITOYLTRANSFERASE;
PHENYLMERCURIC BORATE; ESCHERICHIA-COLI; IN-VITRO; MECHANISM;
INHIBITION; LOCALIZATION; INJECTIONS; MENINGITIS
AB A recent large outbreak of fungal infections by Exserohilum rostratum from contaminated compounding solutions has highlighted the need to rapidly screen available pharmaceuticals that could be useful in therapy. The present study utilized two newly-developed high throughput assays to screen approved drugs and pharmaceutically active compounds for identification of potential antifungal agents. Several known drugs were found that have potent effects against E. rostratum including the triazole antifungal posaconazole. Posaconazole is likely to be effective against infections involving septic joints and may provide an alternative for refractory central nervous system infections. The anti-E. rostratum activities of several other drugs including bithionol (an anti-parasitic drug), tacrolimus (an immunosuppressive agent) and floxuridine (an antimetabolite) were also identified from the drug repurposing screens. In addition, activities of other potential antifungal agents against E. rostratum were excluded, which may avoid unnecessary therapeutic trials and reveals the limited therapeutic alternatives for this outbreak. In summary, this study has demonstrated that drug repurposing screens can be quickly conducted within a useful time-frame. This would allow clinical implementation of identified alternative therapeutics and should be considered as part of the initial public health response to new outbreaks or rapidly-emerging microbial pathogens.
C1 [Sun, Wei; Southall, Noel; Shinn, Paul; McKew, John C.; Zheng, Wei] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
[Park, Yoon-Dong; Sugui, Janyce A.; Kwon-Chung, Kyung J.; Williamson, Peter R.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Fothergill, Annette] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Williamson, Peter R.] Univ Illinois, Coll Med, Sect Infect Dis Immunol & Int Med, Chicago, IL USA.
RP Zheng, W (reprint author), NIH, Natl Ctr Adv Translat Sci, Bldg 10, Bethesda, MD 20892 USA.
EM wzheng@mail.nih.gov; williamsonpr@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 Program of the National Center for Advancing
Translational Sciences; Intramural Research Program of the National
Institute of Allergy and Infectious Diseases, National Institutes of
Health
FX This work was supported by the Intramural Research Programs of the
National Center for Advancing Translational Sciences and National
Institute of Allergy and Infectious Diseases, National Institutes of
Health. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 49
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U1 0
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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 AUG 21
PY 2013
VL 8
IS 8
AR e70506
DI 10.1371/journal.pone.0070506
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 218YW
UT WOS:000324470100027
PM 23990907
ER
PT J
AU Briggs, JP
Killen, J
AF Briggs, Josephine P.
Killen, Jack
TI Perspectives on Complementary and Alternative Medicine Research
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
C1 [Briggs, Josephine P.; Killen, Jack] NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA.
RP Briggs, JP (reprint author), Natl Ctr Complementary & Alternat Med, 31 Ctr Dr,Bldg 31,Ste 2B11, Bethesda, MD 20814 USA.
EM briggsj@mail.nih.gov
NR 7
TC 6
Z9 6
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 AUG 21
PY 2013
VL 310
IS 7
BP 691
EP 692
DI 10.1001/jama.2013.6540
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 202XP
UT WOS:000323254500015
PM 23990064
ER
PT J
AU Feenstra, B
Geller, F
Carstensen, L
Romitti, PA
Korberg, IB
Bedell, B
Krogh, C
Fan, RZ
Svenningsson, A
Caggana, M
Nordenskjold, A
Mills, JL
Murray, JC
Melbye, M
AF Feenstra, Bjarke
Geller, Frank
Carstensen, Lisbeth
Romitti, Paul A.
Korberg, Izabella Baranowska
Bedell, Bruce
Krogh, Camilla
Fan, Ruzong
Svenningsson, Anna
Caggana, Michele
Nordenskjold, Agneta
Mills, James L.
Murray, Jeffrey C.
Melbye, Mads
TI Plasma Lipids, Genetic Variants Near APOA1, and the Risk of Infantile
Hypertrophic Pyloric Stenosis
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; LEMLI-OPITZ-SYNDROME; INTERSTITIAL-CELLS;
CHOLESTEROL; METAANALYSIS; CAJAL; EPIDEMIOLOGY; OUTGROWTH; NERVES;
COHORT
AB IMPORTANCE Infantile hypertrophic pyloric stenosis (IHPS) is a serious condition in which hypertrophy of the pyloric sphincter muscle layer leads to gastric outlet obstruction. Infantile hypertrophic pyloric stenosis shows strong familial aggregation and heritability, but knowledge about specific genetic risk variants is limited.
OBJECTIVES To search the genome comprehensively for genetic associations with IHPS and validate findings in 3 independent sample sets.
DESIGN, SETTING, AND PARTICIPANTS During stage 1, we used reference data from the 1000 Genomes Project for imputation into a genome-wide data set of 1001 Danish surgery-confirmed samples (cases diagnosed 1987-2008) and 2371 disease-free controls. In stage 2, the 5 most significantly associated loci were tested in independent case-control sample sets from Denmark (cases diagnosed 1983-2010), Sweden (cases diagnosed 1958-2011), and the United States (cases diagnosed 1998-2005), with a total of 1663 cases and 2315 controls.
MAIN OUTCOMES AND MEASURES Association of genetic variation with the presence of infantile hypertrophic pyloric stenosis.
RESULTS We found a new genome-wide significant locus for IHPS at chromosome 11q23.3. The single-nucleotide polymorphism (SNP) with the lowest P value at the locus, rs12721025 (odds ratio [OR], 1.59; 95% CI, 1.38-1.83; P = 1.9 x 10(-10)), is located 301 bases downstream of the apolipoprotein A-I (APOA1) gene and is correlated (r(2) between 0.46 and 0.80) with SNPs previously found to be associated with levels of circulating cholesterol. For these SNPs, the cholesterol-lowering allele consistently was associated with increased risk of IHPS.
CONCLUSIONS AND RELEVANCE This study identified a new genome-wide significant locus for IHPS. Characteristics of this locus suggest the possibility of an inverse relationship between levels of circulating cholesterol in neonates and IHPS risk, which warrants further investigation.
C1 [Feenstra, Bjarke; Geller, Frank; Carstensen, Lisbeth; Krogh, Camilla; Melbye, Mads] Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen S, Denmark.
[Romitti, Paul A.] Univ Iowa, Dept Epidemiol, Iowa City, IA USA.
[Korberg, Izabella Baranowska; Svenningsson, Anna; Nordenskjold, Agneta] Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.
[Korberg, Izabella Baranowska; Svenningsson, Anna; Nordenskjold, Agneta] Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.
[Bedell, Bruce; Murray, Jeffrey C.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA.
[Fan, Ruzong; Mills, James L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Caggana, Michele] New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12237 USA.
RP Feenstra, B (reprint author), Statens Serum Inst, Dept Epidemiol Res, Artillerivej 5, DK-2300 Copenhagen S, Denmark.
EM fee@ssi.dk
OI Nordenskjold, Agneta/0000-0001-6638-4631; Feenstra,
Bjarke/0000-0003-1478-649X
FU Lundbeck Foundation [R34-A3931]; Novo Nordisk Foundation; Danish Medical
Research Council [271-06-0628]; Swedish Research Council; Centers for
Disease Control and Prevention [5U01DD000492]; Intramural Research
Program of the Eunice Kennedy Shriver National Institute of Child Health
and Human Development; National Institutes of Health Genes, Environment,
and Health Initiative [U01HG004423]; Oak Foundation Fellowship
FX The study was supported by grants from the Lundbeck Foundation
(R34-A3931), the Novo Nordisk Foundation, the Danish Medical Research
Council (271-06-0628), the Swedish Research Council, the Centers for
Disease Control and Prevention (5U01DD000492), and the Intramural
Research Program of the Eunice Kennedy Shriver National Institute of
Child Health and Human Development. The GWAS data for the control
samples were generated for our study of preterm birth within the GENEVA
consortium with funding provided through the National Institutes of
Health Genes, Environment, and Health Initiative (U01HG004423). Dr
Feenstra is supported by an Oak Foundation Fellowship.
NR 42
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PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD AUG 21
PY 2013
VL 310
IS 7
BP 714
EP 721
DI 10.1001/jama.2013.242978
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 202XP
UT WOS:000323254500021
PM 23989729
ER
PT J
AU Mascia, F
Lam, G
Keith, C
Garber, C
Steinberg, SM
Kohn, E
Yuspa, SH
AF Mascia, Francesca
Lam, Gary
Keith, Christopher
Garber, Caroline
Steinberg, Seth M.
Kohn, Elise
Yuspa, Stuart H.
TI Genetic Ablation of Epidermal EGFR Reveals the Dynamic Origin of Adverse
Effects of Anti-EGFR Therapy
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; HAIR FOLLICLE;
CHEMOKINE EXPRESSION; TARGETED DISRUPTION; SKIN INFLAMMATION; MICE;
CANCER; DIFFERENTIATION; GEFITINIB
AB Cancer patients treated with anti-EGFR (epidermal growth factor receptor) drugs often develop a dose-limiting pruritic rash of unknown etiology. The aims of our study were to define causal associations from a clinical study of cutaneous and systemic changes in patients treated with gefitinib and use these to develop and characterize a mouse model that recapitulates the human skin rash syndrome caused by anti-EGFR therapy. We examined the patients' plasma before and after treatment with gefitinib and documented changes in chemokines and leukocyte counts associated with the extent of rash or the presence of pruritus. We established a parallel mouse model by ablating EGFR in the epidermis. These mice developed skin lesions similar to the human rash. Before lesion development, we detected increased mRNA expression of chemokines in the skin associated with early infiltration of macrophages and mast cells and later infiltration of eosinophils, T cells, and neutrophils. As the skin phenotype evolved, changes in blood counts and circulating chemokines reproduced those seen in the gefitinib-treated patients. Crossing the mutant mice with mice deficient for tumor necrosis factor-alpha (TNF-alpha) receptors, MyD88, NOS2, CCR2, T cells, or B cells failed to reverse the skin phenotype. However, local depletion of macrophages provided partial resolution, suggesting that this model can identify targets that may be effective in preventing the troublesome and dose-limiting skin response to anti-EGFR drugs. These results highlight the importance of EGFR signaling in maintaining skin immune homeostasis and identify a macrophage contribution to a serious adverse consequence of cancer chemotherapy.
C1 [Mascia, Francesca; Lam, Gary; Keith, Christopher; Garber, Caroline; Yuspa, Stuart H.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20852 USA.
[Kohn, Elise] NCI, Mol Signaling Sect, Med Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
RP Yuspa, SH (reprint author), NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM yuspas@mail.nih.gov
FU Center for Cancer Research Intramural Program of the NIH
FX This work was supported by the Center for Cancer Research Intramural
Program of the NIH.
NR 39
TC 7
Z9 7
U1 0
U2 2
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
EI 1946-6242
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD AUG 21
PY 2013
VL 5
IS 199
AR 200ra116
DI 10.1126/scitranslmed.3006504
PG 12
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 205DT
UT WOS:000323422600008
ER
PT J
AU Bender, JLG
Lee, A
Reid, JM
Baruchel, S
Roberts, T
Voss, SD
Wu, B
Ahern, CH
Ingle, AM
Harris, P
Weigel, BJ
Blaney, SM
AF Bender, Julia L. Glade
Lee, Alice
Reid, Joel M.
Baruchel, Sylvain
Roberts, Timothy
Voss, Stephan D.
Wu, Bing
Ahern, Charlotte H.
Ingle, Ashish M.
Harris, Pamela
Weigel, Brenda J.
Blaney, Susan M.
TI Phase I Pharmacokinetic and Pharmacodynamic Study of Pazopanib in
Children With Soft Tissue Sarcoma and Other Refractory Solid Tumors: A
Children's Oncology Group Phase I Consortium Report
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID MULTIKINASE ANGIOGENESIS INHIBITOR; CANCER-PATIENTS; PEDIATRIC-PATIENTS;
COLORECTAL-CANCER; KINASE INHIBITOR; ORAL PAZOPANIB; TRIAL; BIOMARKER;
HYPERTENSION; SUNITINIB
AB Purpose
Pazopanib, an oral multikinase angiogenesis inhibitor, prolongs progression-free survival in adults with soft tissue sarcoma (STS). A phase I pharmacokinetic and pharmacodynamic study of two formulations of pazopanib was performed in children with STS or other refractory solid tumors.
Patients and Methods
Pazopanib (tablet formulation) was administered once daily in 28-day cycles at four dose levels (275 to 600 mg/m(2)) using the rolling-six design. Dose determination for a powder suspension was initiated at 50% of the maximum-tolerated dose (MTD) for the intact tablet. Ten patients with STS underwent dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) scanning at baseline and 15 +/- 2 days after initiation of pazopanib at the tablet MTD.
Results
Fifty-three patients were enrolled; 51 were eligible (26 males; median age, 12.9 years; range, 3.8 to 23.9 years). Hematologic and nonhematologic toxicities were generally mild, with dose-limiting lipase, amylase, and ALT elevation, proteinuria, and hypertension. One patient with occult brain metastasis had grade 4 intracranial hemorrhage. The MTD was 450 mg/m(2) for tablet and 160 mg/m(2) for suspension. Steady-state trough concentrations were reached by day 15 and did not seem to be dose dependent. One patient each with hepatoblastoma or desmoplastic small round cell tumor achieved a partial response; eight patients had stable disease for >= six cycles, seven of whom had sarcoma. All patients with evaluable DCE-MRI (n = 8) experienced decreases in tumor blood volume and permeability (P < .01). Placental growth factor increased, whereas endoglin and soluble vascular endothelial growth factor receptor-2 decreased (P < .01; n = 41).
Conclusion
Pazopanib is well tolerated in children, with evidence of antiangiogenic effect and potential clinical benefit in pediatric sarcoma. (C) 2013 by American Society of Clinical Oncology
C1 [Bender, Julia L. Glade; Lee, Alice] Columbia Univ, Med Ctr, New York, NY 10032 USA.
[Reid, Joel M.] Mayo Clin, Ctr Canc, Rochester, MN USA.
[Weigel, Brenda J.] Univ Minnesota, Amplatz Childrens Hosp, Minneapolis, MN USA.
[Roberts, Timothy] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Voss, Stephan D.] Boston Childrens Hosp, Boston, MA USA.
[Ahern, Charlotte H.; Blaney, Susan M.] Texas Childrens Canc Ctr, Houston, TX USA.
[Ingle, Ashish M.] Childrens Oncol Grp, Operat Ctr, Arcadia, CA USA.
[Harris, Pamela] NCI, Canc Treatment Expt Program, Bethesda, MD 20892 USA.
[Baruchel, Sylvain; Wu, Bing] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
RP Bender, JLG (reprint author), Columbia Univ, Div Pediat Oncol, 161 Ft Washington Ave,IP-7, New York, NY 10032 USA.
EM Jg589@columbia.edu
FU Alex's Lemonade Stand Foundation; Columbia University's Clinical and
Translational Science Awards [UL1RR024156]; GlaxoSmithKline; Phase
I/Pilot Consortium Grant of the Children's Oncology Group from the
National Cancer Institute, National Institutes of Health, Bethesda, MD
[U01 CA97452]
FX Supported in part by Alex's Lemonade Stand Foundation, Columbia
University's Clinical and Translational Science Awards Grant No.
UL1RR024156, GlaxoSmithKline, and the Phase I/Pilot Consortium Grant No.
U01 CA97452 of the Children's Oncology Group from the National Cancer
Institute, National Institutes of Health, Bethesda, MD.
NR 29
TC 30
Z9 32
U1 1
U2 3
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD AUG 20
PY 2013
VL 31
IS 24
BP 3034
EP U88
DI 10.1200/JCO.2012.47.0914
PG 15
WC Oncology
SC Oncology
GA 301NW
UT WOS:000330540000016
ER
PT J
AU Xue, L
Cai, JY
Ma, J
Huang, Z
Guo, MX
Fu, LZ
Shi, YB
Li, WX
AF Xue, Lu
Cai, Jin-Yang
Ma, Jian
Huang, Zan
Guo, Ming-Xiong
Fu, Lie-Zhen
Shi, Yun-Bo
Li, Wen-Xin
TI Global expression profiling reveals genetic programs underlying the
developmental divergence between mouse and human embryogenesis
SO BMC GENOMICS
LA English
DT Article
DE Microarray; Mouse embryogenesis; Human embryogenesis; Organogenesis;
Evolution; Protein interaction network
ID HUMAN PREIMPLANTATION DEVELOPMENT; EMBRYONIC STEM-CELLS; INTERACTION
NETWORKS; TRANSCRIPTOME ANALYSIS; CDNA MICROARRAY; HUMAN OOCYTES;
GENOME-WIDE; BLASTOCYST; ORGANOGENESIS; GASTRULATION
AB Background: Mouse has served as an excellent model for studying human development and diseases due to its similarity to human. Advances in transgenic and knockout studies in mouse have dramatically strengthened the use of this model and significantly improved our understanding of gene function during development in the past few decades. More recently, global gene expression analyses have revealed novel features in early embryogenesis up to gastrulation stages and have indeed provided molecular evidence supporting the conservation in early development in human and mouse. On the other hand, little information is known about the gene regulatory networks governing the subsequent organogenesis. Importantly, mouse and human development diverges during organogenesis. For instance, the mouse embryo is born around the end of organogenesis while in human the subsequent fetal period of ongoing growth and maturation of most organs spans more than 2/3 of human embryogenesis. While two recent studies reported the gene expression profiles during human organogenesis, no global gene expression analysis had been done for mouse organogenesis.
Results: Here we report a detailed analysis of the global gene expression profiles from egg to the end of organogenesis in mouse. Our studies have revealed distinct temporal regulation patterns for genes belonging to different functional (Gene Ontology or GO) categories that support their roles during organogenesis. More importantly, comparative analyses identify both conserved and divergent gene regulation programs in mouse and human organogenesis, with the latter likely responsible for the developmental divergence between the two species, and further suggest a novel developmental strategy during vertebrate evolution.
Conclusions: We have reported here the first genome-wide gene expression analysis of the entire mouse embryogenesis and compared the transcriptome atlas during mouse and human embryogenesis. Given our earlier observation that genes function in a given process tends to be developmentally co-regulated during organogenesis, our microarray data here should help to identify genes associated with mouse development and/or infer the developmental functions of unknown genes. In addition, our study might be useful for invesgtigating the molecular basis of vertebrate evolution.
C1 [Xue, Lu; Cai, Jin-Yang; Ma, Jian; Huang, Zan; Guo, Ming-Xiong; Li, Wen-Xin] Wuhan Univ, Coll Life Sci, Wuhan 430072, Peoples R China.
[Xue, Lu] South Cent Univ Nationalities, Coll Life Sci, Inst Med Biol, Wuhan 430074, Peoples R China.
[Fu, Lie-Zhen; Shi, Yun-Bo] NICHD, Sect Mol Morphogenesis, Program Cellular Regulat & Metab, NIH, Bethesda, MD 20892 USA.
RP Shi, YB (reprint author), NICHD, Sect Mol Morphogenesis, Program Cellular Regulat & Metab, NIH, Bethesda, MD 20892 USA.
EM shi@helix.nih.gov; liwxlab@whu.edu.cn
FU National High Technology Research and Development Program of China (863
Program) [2006AA02A306]; National Natural Science Foundation of China
[31271511, 31101047, 81070406]; Research Fund for the Doctoral Program
of Higher Education of China [20110141110016]; Intramural Research
Program of NICHD, National Institutes of Health
FX We would like to thank Drs. Yu Song, zhongjie Li, Yi Lin, Haiming Hu,
Wei Wang for helpful assistance and contributions in the preparation of
this manuscript. We thank all the teachers and students from the lab of
Virology and Molecular Oncology for their discussions and comments that
improved the manuscript. This work was supported by National High
Technology Research and Development Program of China (863 Program) Grant
2006AA02A306, National Natural Science Foundation of China Grant
31271511, 31101047 and 81070406, Research Fund for the Doctoral Program
of Higher Education of China Grant 20110141110016. YBS and LF were
supported by the Intramural Research Program of NICHD, National
Institutes of Health.
NR 59
TC 5
Z9 5
U1 3
U2 12
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD AUG 20
PY 2013
VL 14
AR 568
DI 10.1186/1471-2164-14-568
PG 16
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 274SC
UT WOS:000328625500001
PM 23961710
ER
PT J
AU Mihaescu, R
Pencina, MJ
Alonso, A
Lunetta, KL
Heckbert, SR
Benjamin, EJ
Janssens, ACJW
AF Mihaescu, Raluca
Pencina, Michael J.
Alonso, Alvaro
Lunetta, Kathryn L.
Heckbert, Susan R.
Benjamin, Emelia J.
Janssens, A. Cecile J. W.
TI Incremental value of rare genetic variants for the prediction of
multifactorial diseases
SO GENOME MEDICINE
LA English
DT Article
ID ATRIAL-FIBRILLATION; ATHEROSCLEROSIS RISK; COMPLEX DISEASES; COMMON;
SUSCEPTIBILITY; IDENTIFICATION; PERFORMANCE; BIOMARKERS; COMMUNITY;
DESIGN
AB Background: It is often assumed that rare genetic variants will improve available risk prediction scores. We aimed to estimate the added predictive ability of rare variants for risk prediction of common diseases in hypothetical scenarios.
Methods: In simulated data, we constructed risk models with an area under the ROC curve (AUC) ranging between 0.50 and 0.95, to which we added a single variant representing the cumulative frequency and effect (odds ratio, OR) of multiple rare variants. The frequency of the rare variant ranged between 0.0001 and 0.01 and the OR between 2 and 10. We assessed the resulting AUC, increment in AUC, integrated discrimination improvement (IDI), net reclassification improvement (NRI(>0.01)) and categorical NRI. The analyses were illustrated by a simulation of atrial fibrillation risk prediction based on a published clinical risk model.
Results: We observed minimal improvement in AUC with the addition of rare variants. All measures increased with the frequency and OR of the variant, but maximum increment in AUC remained below 0.05. Increment in AUC and NRI(>0.01) decreased with higher AUC of the baseline model, whereas IDI remained constant. In the atrial fibrillation example, the maximum increment in AUC was 0.02 for a variant with frequency = 0.01 and OR = 10. IDI and NRI showed at most minimal increase for variants with frequency greater than or equal to 0.005 and OR greater than or equal to 5.
Conclusions: Since rare variants are present in only a minority of affected individuals, their predictive ability is generally low at the population level. To improve the predictive ability of clinical risk models for complex diseases, genetic variants must be common and have substantial effect on disease risk.
C1 [Mihaescu, Raluca; Janssens, A. Cecile J. W.] Erasmus Univ, Med Ctr, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands.
[Pencina, Michael J.; Lunetta, Kathryn L.] Boston Univ, Dept Biostat, Boston, MA 02118 USA.
[Pencina, Michael J.] Harvard Clin Res Inst, Boston, MA 02215 USA.
[Alonso, Alvaro] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN 55454 USA.
[Lunetta, Kathryn L.; Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[Heckbert, Susan R.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Cardiol & Prevent Med Sect, Boston, MA 02118 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA.
[Janssens, A. Cecile J. W.] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.
RP Janssens, ACJW (reprint author), Erasmus Univ, Med Ctr, Dept Epidemiol, Dr Molewaterpl 50, NL-3000 CA Rotterdam, Netherlands.
EM cecile.janssens@emory.edu
RI Alonso, Alvaro/A-4917-2010;
OI Alonso, Alvaro/0000-0002-2225-8323; Janssens, A
Cecile/0000-0002-6153-4976; Benjamin, Emelia/0000-0003-4076-2336
FU Netherlands Organization for Scientific Research; Centre for Medical
Systems Biology in the framework of the Netherlands Genomics Initiative;
Erasmus Trustfonds; National Institutes of Health/American Recovery and
Reinvestment Act Risk Prediction of Atrial Fibrillation [1RC1HL101056];
National Institutes of Health/National Heart, Lung, and Blood Institute
[RC1HL099452, HL068986, HL092577, HL080295, 1R01HL102214, N01-HC 25195];
American Heart Association [09SDG2280087]
FX This work was supported by the Netherlands Organization for Scientific
Research (Vidi grant to ACJWJ); Centre for Medical Systems Biology in
the framework of the Netherlands Genomics Initiative (to ACJWJ); Erasmus
Trustfonds (to RM); National Institutes of Health/American Recovery and
Reinvestment Act Risk Prediction of Atrial Fibrillation (1RC1HL101056 to
MP and EJB); National Institutes of Health/National Heart, Lung, and
Blood Institute (RC1HL099452 to AA; HL068986 to SRH; HL092577 to EJB,
KLL, and SRH; HL080295 to SRH; 1R01HL102214 to EJB; N01-HC 25195 to
EJB); and the American Heart Association (09SDG2280087 to AA).
NR 41
TC 4
Z9 4
U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1756-994X
J9 GENOME MED
JI Genome Med.
PD AUG 20
PY 2013
VL 5
AR 76
DI 10.1186/gm480
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 246OD
UT WOS:000326547300001
PM 23961719
ER
PT J
AU Chen, Y
Chatterjee, SS
Porcella, SF
Yu, YS
Otto, M
AF Chen, Yan
Chatterjee, Som S.
Porcella, Stephen F.
Yu, Yun-Song
Otto, Michael
TI Complete Genome Sequence of a Panton-Valentine Leukocidin-Negative
Community-Associated Methicillin-Resistant Staphylococcus aureus Strain
of Sequence type 72 from Korea
SO PLOS ONE
LA English
DT Article
ID VIRULENCE DETERMINANTS; SOUTH-KOREA; MRSA; INFECTION; USA300; GENES
AB In the past decade, community-associated (CA-) infections with methicillin-resistant Staphylococcus aureus (MRSA) have emerged throughout the world. Different CA-MRSA strains dominate in different geographical locations. Many CA-MRSA lineages contain genes coding for the Panton-Valentine leukocidin. However, the role of this leukotoxin in CA-MRSA pathogenesis is still controversial. The genome sequences of two key PVL-positive CA-MRSA strains (USA300, USA400) have been reported, but we lack information on the more recently found PVL-negative CA-MRSA strains. One such strain is the PVL-negative ST72, the main cause of CA-MRSA infections in Korea. Here, we report the entire genome sequence of CA-MRSA ST72 and analyze its gene content with a focus on virulence factors. Our results show that this strain does not have considerable differences in virulence factor content compared to other CA-MRSA strains (USA300, USA400), indicating that other toxins do not substitute for the lack of PVL in ST72. This finding is in accordance with the notion that differential expression of widespread virulence determinants, rather than the acquisition of additional virulence factors on mobile genetic elements, such as PVL, is responsible for the increased virulence of CA-compared to hospital-associated MRSA.
C1 [Chen, Yan; Chatterjee, Som S.; Otto, Michael] Natl Inst Allergy & Infect Dis, US Natl Inst Hlth, Lab Human Bacterial Pathogenesis, Pathogen Mol Genet Sect, Bethesda, MD USA.
[Chen, Yan; Yu, Yun-Song] Zhejiang Univ, Coll Med, Sir Run Run Shaw Hosp, Dept Infect Dis, Hangzhou 310027, Peoples R China.
[Porcella, Stephen F.] Natl Inst Allergy & Infect Dis, US Natl Inst Hlth, Res Technol Branch, Genom Unit, Hamilton, MT USA.
RP Otto, M (reprint author), Natl Inst Allergy & Infect Dis, US Natl Inst Hlth, Lab Human Bacterial Pathogenesis, Pathogen Mol Genet Sect, Bethesda, MD USA.
EM motto@niaid.nih.gov
OI Chen, Yan/0000-0002-7679-1713; Otto, Michael/0000-0002-2222-4115
FU Intramural Program of the NIAID [ZIA AI000904-12]; Ministry of Health of
the People's Republic of China [201002021]
FX Intramural Program of the NIAID (ZIA AI000904-12); Ministry of Health of
the People's Republic of China (no. 201002021). The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 27
TC 8
Z9 8
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 AUG 20
PY 2013
VL 8
IS 8
AR e72803
DI 10.1371/journal.pone.0072803
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 219RU
UT WOS:000324527300098
PM 23977354
ER
PT J
AU Kang, DW
Luecke, HF
AF Kang, Dong Wook
Luecke, Hans F.
TI Facile Synthetic Routes to Prepare alpha-Muricholic Acid, Hyocholic
Acid, and Their Taurine Conjugates
SO BULLETIN OF THE KOREAN CHEMICAL SOCIETY
LA English
DT Article
DE Bile acids; alpha-Muricholic acid; Hyocholic acid; Taurine conjugates;
Metabolites
ID BILE-ACID; EFFICIENT SYNTHESIS; METABOLITES; PEPTIDE
AB alpha-Muricholic acid was synthesized through 9 steps from chenodeoxycholic acid with 26% overall yield. Hyocholic acid was synthesized through 8 steps from the same starting material with 63% overall yield. Taurine conjugates of alpha-muricholic acid and hyocholic acid were also prepared via their pentafluorophenyl ester.
C1 [Kang, Dong Wook] Catholic Univ Daegu, Dept Pharmaceut Sci & Technol, Kyeongsangbuk Do 712702, South Korea.
[Luecke, Hans F.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Kang, DW (reprint author), Catholic Univ Daegu, Dept Pharmaceut Sci & Technol, Kyeongsangbuk Do 712702, South Korea.
EM dwkang@cu.ac.kr; lueckeh@mail.nih.gov
FU National Institutes of Health Intramural Research Program (NIDDK);
Catholic University of Daegu
FX We are extremely grateful to Drs. Matsubara Tsutomu, and Jooyoun Cho for
their kind discussion, support, and collaboration. This work was
supported by the National Institutes of Health Intramural Research
Program (NIDDK) and Catholic University of Daegu.
NR 15
TC 0
Z9 1
U1 1
U2 6
PU KOREAN CHEMICAL SOC
PI SEOUL
PA 635-4 YEOGSAM-DONG, KANGNAM-GU, SEOUL 135-703, SOUTH KOREA
SN 0253-2964
EI 1229-5949
J9 B KOREAN CHEM SOC
JI Bull. Korean Chem. Soc.
PD AUG 20
PY 2013
VL 34
IS 8
BP 2436
EP 2440
DI 10.5012/bkcs.2013.34.8.2436
PG 5
WC Chemistry, Multidisciplinary
SC Chemistry
GA 210SI
UT WOS:000323854400040
ER
PT J
AU Bok, J
Zenczak, C
Hwang, CH
Wu, DK
AF Bok, Jinwoong
Zenczak, Colleen
Hwang, Chan Ho
Wu, Doris K.
TI Auditory ganglion source of Sonic hedgehog regulates timing of cell
cycle exit and differentiation of mammalian cochlear hair cells
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE morphogenesis; Atoh1; tonotopy
ID INNER-EAR DEVELOPMENT; FATE DETERMINATION; FOXG1; MICE; IDENTIFICATION;
SPECIFICATION; MORPHOGENESIS; EXPRESSION; NEURONS; ORGAN
AB Neural precursor cells of the central nervous system undergo successive temporal waves of terminal division, each of which is soon followed by the onset of cell differentiation. The organ of Corti in the mammalian cochlea develops differently, such that precursors at the apex are the first to exit from the cell cycle but the last to begin differentiating as mechanosensory hair cells. Using a tissue-specific knockout approach in mice, we show that this unique temporal pattern of sensory cell development requires that the adjacent auditory (spiral) ganglion serve as a source of the signaling molecule Sonic hedgehog (Shh). In the absence of this signaling, the cochlear duct is shortened, sensory hair cell precursors exit from the cell cycle prematurely, and hair cell differentiation closely follows cell cycle exit in a similar apical-to-basal direction. The dynamic relationship between the restriction of Shh expression in the developing spiral ganglion and its proximity to regions of the growing cochlear duct dictates the timing of terminal mitosis of hair cell precursors and their subsequent differentiation.
C1 [Bok, Jinwoong] Yonsei Univ, Coll Med, Dept Anat, Dept Otorhinolaryngol,Project Med Sci BK21, Seoul 120752, South Korea.
[Zenczak, Colleen; Hwang, Chan Ho; Wu, Doris K.] Natl Inst Deafness & Other Commun Disorders, Mol Biol Lab, Rockville, MD 20850 USA.
RP Bok, J (reprint author), Yonsei Univ, Coll Med, Dept Anat, Dept Otorhinolaryngol,Project Med Sci BK21, Seoul 120752, South Korea.
EM bokj@yuhs.ac; wud@nidcd.nih.gov
RI Bok, Jinwoong/B-8982-2016
OI Bok, Jinwoong/0000-0003-1958-1872
FU National Research Foundation of Korea [2011-0028066, 2012R1A1A2041348];
National Institute on Deafness and Other Communication Disorders
FX We thank Drs. Lisa Goodrich, Jane Johnson, and Susan McConnell for mice
and Drs. Lisa Cunningham, Douglas Epstein, Thomas Friedman, Andrew
Griffith, James Keller, and Steven Raft for critical reading of the
manuscript. This work was supported by the National Research Foundation
of Korea (Grants 2011-0028066 and 2012R1A1A2041348, to J.B.) and the
National Institute on Deafness and Other Communication Disorders
Intramural Program (D.K.W.).
NR 30
TC 18
Z9 18
U1 0
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 AUG 20
PY 2013
VL 110
IS 34
BP 13869
EP 13874
DI 10.1073/pnas.1222341110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 203DU
UT WOS:000323271400049
PM 23918393
ER
PT J
AU Furness, DN
Johnson, SL
Manor, U
Ruttiger, L
Tocchetti, A
Offenhauser, N
Olt, J
Goodyear, RJ
Vijayakumar, S
Dai, YH
Hackney, CM
Franz, C
Di Fiore, PP
Masetto, S
Jones, SM
Knipper, M
Holley, MC
Richardson, GP
Kachar, B
Marcotti, W
AF Furness, David N.
Johnson, Stuart L.
Manor, Uri
Ruettiger, Lukas
Tocchetti, Arianna
Offenhauser, Nina
Olt, Jennifer
Goodyear, Richard J.
Vijayakumar, Sarath
Dai, Yuhai
Hackney, Carole M.
Franz, Christoph
Di Fiore, Pier Paolo
Masetto, Sergio
Jones, Sherri M.
Knipper, Marlies
Holley, Matthew C.
Richardson, Guy P.
Kachar, Bechara
Marcotti, Walter
TI Progressive hearing loss and gradual deterioration of sensory hair
bundles in the ears of mice lacking the actin-binding protein Eps8L2
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE deafness; sensory system; ion channel
ID CELL STEREOCILIA; MYOSIN-XVA; FILAMENTS; GROWTH; ESPIN; MAINTENANCE;
ADAPTATION; ELONGATION; DEAFNESS; DEFECTS
AB Mechanotransduction in the mammalian auditory system depends on mechanosensitive channels in the hair bundles that project from the apical surface of the sensory hair cells. Individual stereocilia within each bundle contain a core of tightly packed actin filaments, whose length is dynamically regulated during development and in the adult. We show that the actin-binding protein epidermal growth factor receptor pathway substrate 8 (Eps8)L2, a member of the Eps8-like protein family, is a newly identified hair bundle protein that is localized at the tips of stereocilia of both cochlear and vestibular hair cells. It has a spatiotemporal expression pattern that complements that of Eps8. In the cochlea, whereas Eps8 is essential for the initial elongation of stereocilia, Eps8L2 is required for their maintenance in adult hair cells. In the absence of both proteins, the ordered staircase structure of the hair bundle in the cochlea decays. In contrast to the early profound hearing loss associated with an absence of Eps8, Eps8L2 null-mutant mice exhibit a late-onset, progressive hearing loss that is directly linked to a gradual deterioration in hair bundle morphology. We conclude that Eps8L2 is required for the long-term maintenance of the staircase structure and mechanosensory function of auditory hair bundles. It complements the developmental role of Eps8 and is a candidate gene for progressive age-related hearing loss.
C1 [Furness, David N.] Keele Univ, Inst Sci & Technol Med, Keele ST5 5BG, Staffs, England.
[Johnson, Stuart L.; Olt, Jennifer; Hackney, Carole M.; Holley, Matthew C.; Marcotti, Walter] Univ Sheffield, Dept Biomed Sci, Sheffield S10 2TN, S Yorkshire, England.
[Manor, Uri; Dai, Yuhai; Kachar, Bechara] Natl Inst Deafness & Other Commun Disorders, Lab Cell Struct & Dynam, NIH, Bethesda, MD 20892 USA.
[Ruettiger, Lukas; Franz, Christoph; Knipper, Marlies] Univ Tubingen, Tubingen Hearing Res Ctr, Dept Otolaryngol, D-72076 Tubingen, Germany.
[Tocchetti, Arianna; Offenhauser, Nina; Di Fiore, Pier Paolo] Fdn Ist FIRC Oncol Mol IFOM, I-20139 Milan, Italy.
[Goodyear, Richard J.; Richardson, Guy P.] Univ Sussex, Sch Life Sci, Brighton BN1 9QG, E Sussex, England.
[Vijayakumar, Sarath; Jones, Sherri M.] Univ Nebraska, Dept Special Educ & Commun Disorders, Lincoln, NE 68583 USA.
[Di Fiore, Pier Paolo] Ist Europeo Oncol, I-20141 Milan, Italy.
[Di Fiore, Pier Paolo] Univ Milan, Dipartimento Sci Salute, I-20122 Milan, Italy.
[Masetto, Sergio] Univ Pavia, Dept Physiol & Pharmacol Sci, I-27100 Pavia, Italy.
RP Marcotti, W (reprint author), Univ Sheffield, Dept Biomed Sci, Sheffield S10 2TN, S Yorkshire, England.
EM w.marcotti@sheffield.ac.uk
RI Di Fiore, Pier Paolo/K-2130-2012;
OI Di Fiore, Pier Paolo/0000-0002-2252-0950; Offenhauser,
Nina/0000-0002-3316-3047; Holley, Matthew/0000-0001-9547-1953
FU Wellcome Trust [091895, 087737]; Westfield Health; fondazione cariplo
[2012/5746]; Deutsche Forschungsgemeinschaft [DFG Kni 316-4-1];
Intramural Programs of the National Institute on Deafness and Other
Communication Disorders; Nebraska Tobacco Settlement Biomedical Research
Development Fund
FX We thank Choongheon Lee for assistance with VsEP data collection. This
work was supported by the following grants: Wellcome Trust (091895) and
Westfield Health (W.M.), the fondazione cariplo (2012/5746) (to W.M. and
S.M.), the Wellcome Trust (087737) (to G.P.R.), Deutsche
Forschungsgemeinschaft DFG Kni 316-4-1 (to M.K.), the Intramural
Programs of the National Institute on Deafness and Other Communication
Disorders (B.K.), and the Nebraska Tobacco Settlement Biomedical
Research Development Fund (to S.M.J.). S.L.J. is a Royal Society
University Research Fellow.
NR 40
TC 19
Z9 19
U1 1
U2 13
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD AUG 20
PY 2013
VL 110
IS 34
BP 13898
EP 13903
DI 10.1073/pnas.1304644110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 203DU
UT WOS:000323271400054
PM 23918390
ER
PT J
AU Le, K
Li, CC
Ye, G
Moss, J
Vaughan, M
AF Le, Kang
Li, Chun-Chun
Ye, Guan
Moss, Joel
Vaughan, Martha
TI Arf guanine nucleotide-exchange factors BIG1 and BIG2 regulate nonmuscle
myosin IIA activity by anchoring myosin phosphatase complex
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID ADP-RIBOSYLATION FACTORS; SMOOTH-MUSCLE MYOSIN; LIGHT-CHAIN PHOSPHATASE;
RHO-ASSOCIATED KINASE; PROTEIN PHOSPHATASE-1; CELL-MIGRATION; RECYCLING
ENDOSOMES; REDUNDANT ROLES; INTEGRIN BETA-1; TARGET SUBUNIT
AB Brefeldin A-inhibited guanine nucleotide-exchange factors BIG1 and BIG2 activate, through their Sec7 domains, ADP ribosylation factors (Arfs) by accelerating the replacement of Arf-bound GDP with GTP for initiation of vesicular transport or activation of specific enzymes that modify important phospholipids. They are also implicated in regulation of cell polarization and actin dynamics for directed migration. Reciprocal coimmunoprecipitation of endogenous HeLa cell BIG1 and BIG2 with myosin IIA was demonstrably independent of Arf guanine nucleotide-exchange factor activity, because effects of BIG1 and BIG2 depletion were reversed by overexpression of the cognate BIG molecule C-terminal sequence that follows the Arf activation site. Selective depletion of BIG1 or BIG2 enhanced specific phosphorylation of myosin regulatory light chain (T18/S19) and F-actin content, which impaired cell migration in Transwell assays. Our data are clear evidence of these newly recognized functions for BIG1 and BIG2 in transduction or integration of mechanical signals from integrin adhesions and myosin IIA-dependent actin dynamics. Thus, by anchoring or scaffolding the assembly, organization, and efficient operation of multi-molecular myosin phosphatase complexes that include myosin IIA, protein phosphatase 1 delta, and myosin phosphatase-targeting subunit 1, BIG1 and BIG2 serve to integrate diverse biophysical and biochemical events in cells.
C1 [Le, Kang; Li, Chun-Chun; Ye, Guan; Moss, Joel; Vaughan, Martha] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA.
RP Vaughan, M (reprint author), NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM vaughanm@mail.nih.gov
RI Le, Kang/D-1630-2016
FU Intramural Research Program of the NIH, NHLBI
FX We thank Drs. Robert S. Adelstein and Mary Ann Conti [National Heart,
Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH)]
for their generous provision of expert advice and consultation, in
addition to antibodies against NMHC IIB and IIC; Dr. Zissis C. Chroneos
(The Pennsylvania State University) for his important gift of NMHC IIA
plasmids that enabled us to demonstrate direct interactions of in
vitro-synthesized proteins; and Drs. Daniela Malide and Christian Combs
(Light Microscopy Core Facility, NHLBI) for their invaluable help in
confocal microscopy. This research was supported by the Intramural
Research Program of the NIH, NHLBI.
NR 62
TC 5
Z9 5
U1 1
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 AUG 20
PY 2013
VL 110
IS 34
BP E3162
EP E3170
DI 10.1073/pnas.1312531110
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 203DU
UT WOS:000323271400006
PM 23918382
ER
PT J
AU Yang, RT
Daigle, BJ
Muhie, SY
Hammamieh, R
Jett, M
Petzold, L
Doyle, FJ
AF Yang, Ruoting
Daigle, Bernie J., Jr.
Muhie, Seid Y.
Hammamieh, Rasha
Jett, Marti
Petzold, Linda
Doyle, Francis J., III
TI Core modular blood and brain biomarkers in social defeat mouse model for
post traumatic stress disorder
SO BMC SYSTEMS BIOLOGY
LA English
DT Article
ID GENE-COEXPRESSION NETWORK; BREAST-CANCER METASTASIS; PERIPHERAL-BLOOD;
EXPRESSION PROFILES; DISEASE; PATHWAY; SUSCEPTIBILITY; IDENTIFICATION;
DEPRESSION; DISCOVERY
AB Background: Post-traumatic stress disorder (PTSD) is a severe anxiety disorder that affects a substantial portion of combat veterans and poses serious consequences to long-term health. Consequently, the identification of diagnostic and prognostic blood biomarkers for PTSD is of great interest. Previously, we assessed genome-wide gene expression of seven brain regions and whole blood in a social defeat mouse model subjected to various stress conditions.
Results: To extract biological insights from these data, we have applied a new computational framework for identifying gene modules that are activated in common across blood and various brain regions. Our results, in the form of modular gene networks that highlight spatial and temporal biological functions, provide a systems-level molecular description of response to social stress. Specifically, the common modules discovered between the brain and blood emphasizes molecular transporters in the blood-brain barrier, and the associated genes have significant overlaps with known blood signatures for PTSD, major depression, and bipolar disease. Similarly, the common modules specific to the brain highlight the components of the social defeat stress response (e.g., fear conditioning pathways) in each brain sub-region.
Conclusions: Many of the brain-specific genes discovered are consistent with previous independent studies of PTSD or other mental illnesses. The results from this study further our understanding of the mechanism of stress response and contribute to a growing list of diagnostic biomarkers for PTSD.
C1 [Yang, Ruoting; Petzold, Linda; Doyle, Francis J., III] Univ Calif Santa Barbara, Inst Collaborat Biotechnol, Santa Barbara, CA 93106 USA.
[Daigle, Bernie J., Jr.; Petzold, Linda] Univ Calif Santa Barbara, Dept Comp Sci, Santa Barbara, CA 93106 USA.
[Petzold, Linda] Univ Calif Santa Barbara, Dept Mech Engn, Santa Barbara, CA 93106 USA.
[Doyle, Francis J., III] Univ Calif Santa Barbara, Dept Chem Engn, Santa Barbara, CA 93106 USA.
[Yang, Ruoting; Muhie, Seid Y.; Hammamieh, Rasha; Jett, Marti] USA, Ctr Environm Hlth Res, Ft Detrick, MD USA.
[Yang, Ruoting] Frederick Natl Lab Canc Res, Adv Biomed Comp Ctr, Frederick, MD 21702 USA.
RP Doyle, FJ (reprint author), Univ Calif Santa Barbara, Inst Collaborat Biotechnol, Santa Barbara, CA 93106 USA.
EM doyle@engineering.ucsb.edu
FU U.S. Army Research Office (PTSD) [W911NF-10-2-0111]
FX We gratefully acknowledge financial support from U.S. Army Research
Office (PTSD Grant W911NF-10-2-0111). We also thank the SysBiocube team,
Uma Mudunuri, Sudhir Chowbina, and Raina Kumar, for providing secure
data depository system.
NR 56
TC 6
Z9 6
U1 1
U2 12
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1752-0509
J9 BMC SYST BIOL
JI BMC Syst. Biol.
PD AUG 20
PY 2013
VL 7
AR 80
DI 10.1186/1752-0509-7-80
PG 12
WC Mathematical & Computational Biology
SC Mathematical & Computational Biology
GA 204TH
UT WOS:000323391800001
PM 23962043
ER
PT J
AU Sahebjam, S
Bedard, PL
Castonguay, V
Chen, Z
Reedijk, M
Liu, G
Cohen, B
Zhang, WJ
Clarke, B
Zhang, T
Kamel-Reid, S
Chen, H
Ivy, SP
Razak, ARA
Oza, AM
Chen, EX
Hirte, HW
McGarrity, A
Wang, L
Siu, LL
Hotte, SJ
AF Sahebjam, S.
Bedard, P. L.
Castonguay, V.
Chen, Z.
Reedijk, M.
Liu, G.
Cohen, B.
Zhang, W-J
Clarke, B.
Zhang, T.
Kamel-Reid, S.
Chen, H.
Ivy, S. P.
Razak, A. R. A.
Oza, A. M.
Chen, E. X.
Hirte, H. W.
McGarrity, A.
Wang, L.
Siu, L. L.
Hotte, S. J.
TI A phase I study of the combination of ro4929097 and cediranib in
patients with advanced solid tumours (PJC-004/NCI 8503)
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE RO4929097; cediranib; phase I; combination study
ID GAMMA-SECRETASE INHIBITOR; RENAL-CELL CARCINOMA; BREAST-CANCER;
COLORECTAL-CANCER; UP-REGULATION; DOUBLE-BLIND; GROWTH; ANGIOGENESIS;
EXPRESSION; POOR
AB Background: The Notch signalling pathway has been implicated in tumour initiation, progression, angiogenesis and development of resistance to vascular endothelial growth factor (VEGF) targeting, providing a rationale for the combination of RO4929097, a g-secretase inhibitor, and cediranib, a VEGF receptor tyrosine kinase inhibitor.
Methods: Patients received escalating doses of RO4929097 (on a 3 days-on and 4 days-off schedule) in combination with cediranib (once daily). Cycle 1 was 42 days long with RO4929097 given alone for the first 3 weeks followed by the co-administration of both RO4929097 and cediranib starting from day 22. Cycle 2 and onwards were 21 days long. Soluble markers of angiogenesis were measured in plasma samples. Archival tumour specimens were assessed for expression of three different components of Notch signalling pathway and genotyping.
Results: In total, 20 patients were treated in three dose levels (DLs). The recommended phase II dose was defined as 20 mg for RO4929097 on 3 days-on and 4 days-off schedule and 30 mg daily for cediranib. The most frequent treatment-related adverse events (AEs) were diarrhoea, hypertension, fatigue and nausea. Eleven patients had a best response of stable disease and one patient achieved partial response. We did not detect any correlation between tested biomarkers of angiogenesis or the Notch pathway and treatment effect. There was no correlation between mutational status and time to treatment failure.
Conclusion: RO4929097 in combination with cediranib is generally well tolerated at the DLs tested. Preliminary evidence of antitumour efficacy with prolonged disease stabilisation in some patients with progressive malignancies warrants further clinical investigation of this treatment strategy.
C1 [Sahebjam, S.; Bedard, P. L.; Castonguay, V.; Chen, Z.; Reedijk, M.; Liu, G.; Cohen, B.; Zhang, W-J; Clarke, B.; Zhang, T.; Kamel-Reid, S.; Razak, A. R. A.; Oza, A. M.; Chen, E. X.; McGarrity, A.; Wang, L.; Siu, L. L.] Princess Margaret Hosp, Toronto, ON M5G 2M9, Canada.
[Chen, H.; Ivy, S. P.] NCI, Bethesda, MD 20852 USA.
[Hirte, H. W.; Hotte, S. J.] Juravinski Canc Ctr, Hamilton, ON L8V 5C2, Canada.
RP Hotte, SJ (reprint author), Juravinski Canc Ctr, 699 Concess St, Hamilton, ON L8V 5C2, Canada.
EM sebastien.hotte@jcc.hhsc.ca
RI Liu, Geoffrey/N-4421-2016
FU US National Cancer Institute U01 Cooperative Agreement Award
[U01-CA132123]
FX This study (PJC-004/CTEP 8503) is conducted by the Princess Margaret
Hospital Phase I Consortium with support from the US National Cancer
Institute U01 Cooperative Agreement Award (U01-CA132123).
NR 31
TC 34
Z9 37
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
J9 BRIT J CANCER
JI Br. J. Cancer
PD AUG 20
PY 2013
VL 109
IS 4
BP 943
EP 949
DI 10.1038/bjc.2013.380
PG 7
WC Oncology
SC Oncology
GA 205CA
UT WOS:000323417100017
PM 23868004
ER
PT J
AU Moon, DH
Lee, JM
Noonan, AM
Annunziata, CM
Minasian, L
Houston, N
Hays, JL
Kohn, EC
AF Moon, D. H.
Lee, J-M
Noonan, A. M.
Annunziata, C. M.
Minasian, L.
Houston, N.
Hays, J. L.
Kohn, E. C.
TI Deleterious BRCA1/2 mutation is an independent risk factor for
carboplatin hypersensitivity reactions
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE carboplatin; hypersensitivity; ovarian cancer; deleterious BRCA1/2
mutation
ID OVARIAN-CANCER; CARCINOMA; DESENSITIZATION; MALIGNANCIES; RETREATMENT;
PACLITAXEL; EXPERIENCE; CISPLATIN; SURVIVAL; PREDICT
AB Background: We tested the hypothesis that BRCA1/2 mutation carriers with ovarian cancer are at higher risk of carboplatin hypersensitivity reactions (HSRs).
Methods: Medical records of women enrolled in two carboplatin+olaparib clinical trials (NCT01237067/NCT01445418) were reviewed. A maximum of eight cycles containing carboplatin were administered.
Results: All women (N = 87) had good performance status and end-organ function. Incidences of carboplatin HSR before enrolment and on study were 17% and 21%, respectively. Most patients who developed carboplatin HSR had a deleterious BRCA1/2 mutation (93%) vs 50% in patients without HSR (P<0.0001). Multivariable analysis accounting for potential confounding variables including age, history of allergies, and cumulative prior carboplatin cycles confirmed deleterious BRCA1/2 mutation as an independent risk factor for carboplatin HSR (odds ratio 13.1 (95% confidence interval 2.6-65.4), P = 0.0017). Mutation carriers had onset of carboplatin HSR at lower cumulative exposure (P = 0.003). No significant difference in outcome was observed on our study between patients with and without a history of HSR.
Conclusion: Deleterious BRCA1/2 mutation increased susceptibility and shortened time to carboplatin HSR, independently of other reported factors. These data suggest that at-risk women should be counselled regarding likelihood, symptoms, and potential earlier onset of carboplatin HSRs.
C1 [Moon, D. H.; Lee, J-M; Noonan, A. M.; Annunziata, C. M.; Minasian, L.; Houston, N.; Hays, J. L.; Kohn, E. C.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Moon, D. H.] NIH, Med Res Scholars Program, Bethesda, MD 20892 USA.
RP Lee, JM (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM leej6@mail.nih.gov
RI Annunziata, Christina/L-3219-2016
OI Annunziata, Christina/0000-0003-2033-6532
FU Intramural Program of the Center for Cancer Research, National Cancer
Institute; NIH Medical Research Scholars Program; NIH; Foundation for
the NIH
FX We thank Dr JoAnne Zujewski for her contributions in clinic and Dr Seth
Steinberg for his inputs on the statistical analysis. We also thank I
Prosak and H Minassie for their data management assistance. This work
was supported by the Intramural Program of the Center for Cancer
Research, National Cancer Institute, and olaparib was provided to the
National Cancer Institute by AstraZeneca. DHM was funded through the NIH
Medical Research Scholars Program, a public-private partnership
supported jointly by the NIH and through the Foundation for the NIH
(details on program and donors:
http://www.fnih.org/work/programs-development/medical-research-scholars-
program).
NR 30
TC 13
Z9 14
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
J9 BRIT J CANCER
JI Br. J. Cancer
PD AUG 20
PY 2013
VL 109
IS 4
BP 1072
EP 1078
DI 10.1038/bjc.2013.389
PG 7
WC Oncology
SC Oncology
GA 205CA
UT WOS:000323417100032
PM 23867999
ER
PT J
AU Aoude, LG
Wadt, K
Bojesen, A
Cruger, D
Borg, A
Trent, JM
Brown, KM
Gerdes, AM
Jonsson, G
Hayward, NK
AF Aoude, Lauren G.
Wadt, Karin
Bojesen, Anders
Cruger, Dorthe
Borg, Ake
Trent, Jeffrey M.
Brown, Kevin M.
Gerdes, Anne-Marie
Jonsson, Goran
Hayward, Nicholas K.
TI A BAP1 Mutation in a Danish Family Predisposes to Uveal Melanoma and
Other Cancers
SO PLOS ONE
LA English
DT Article
ID MALIGNANT MESOTHELIOMA; GERMLINE MUTATIONS; TUMORS
AB Truncating germline mutations in the tumor suppressor gene BRCA-1 associated protein-1 (BAP1) have been reported in families predisposed to developing a wide range of different cancer types including uveal melanoma and cutaneous melanoma. There has also been an association between amelanotic tumor development and germline BAP1 mutation suggesting a possible phenotypic characteristic of BAP1 mutation carriers. Though there have been many types of cancer associated with germline BAP1 mutation, the full spectrum of disease association is yet to be ascertained. Here we describe a Danish family with predominantly uveal melanoma but also a range of other tumor types including lung, neuroendocrine, stomach, and breast cancer; as well as pigmented skin lesions. Whole-exome sequencing identified a BAP1 splice mutation located at c.581-2A>G, which leads to a premature truncation of BAP1 in an individual with uveal melanoma. This mutation was carried by several other family members with melanoma or various cancers. The finding expands on the growing profile of BAP1 as an important uveal and cutaneous melanoma tumor suppressor gene and implicates its involvement in the development of lung, and stomach cancer.
C1 [Aoude, Lauren G.; Hayward, Nicholas K.] Queensland Inst Med Res, Oncogen Lab, Brisbane, Qld 4006, Australia.
[Aoude, Lauren G.] Univ Queensland, Brisbane, Qld, Australia.
[Wadt, Karin; Gerdes, Anne-Marie] Rigshosp, Dept Clin Genet, DK-2100 Copenhagen, Denmark.
[Bojesen, Anders; Cruger, Dorthe] Vejle Hosp, Dept Clin Genet, Vejle, Denmark.
[Borg, Ake; Jonsson, Goran] Lund Univ, Div Oncol, Dept Clin Sci Lund, Lund, Sweden.
[Trent, Jeffrey M.; Brown, Kevin M.] Translat Genom Res Inst, Phoenix, AZ USA.
[Brown, Kevin M.] NCI, Lab Translat Genom, Bethesda, MD 20892 USA.
RP Aoude, LG (reprint author), Queensland Inst Med Res, Oncogen Lab, Brisbane, Qld 4006, Australia.
EM lauren.aoude@qimr.edu.au
RI Jonsson, Goran/D-1212-2014; Aoude, Lauren/C-7484-2014; hayward,
nicholas/C-1367-2015
OI Aoude, Lauren/0000-0003-1448-3923; hayward, nicholas/0000-0003-4760-1033
FU Melanoma Research Alliance; Swedish Cancer Society; Swedish Research
Council; Berta Kamprad Foundation; National Health and Medical Research
Council (NHMRC) of Australia; Fight for Sight, Denmark; NHMRC Senior
Principal Research Fellowship; ANZ Ph.D. scholarship
FX This work was supported by the Melanoma Research Alliance, the Swedish
Cancer Society, the Swedish Research Council, the Berta Kamprad
Foundation, the National Health and Medical Research Council (NHMRC) of
Australia, and the Fight for Sight, Denmark. NKH and LGA receive salary
support through a NHMRC Senior Principal Research Fellowship and ANZ
Ph.D. scholarship, respectively. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 17
TC 21
Z9 22
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 19
PY 2013
VL 8
IS 8
AR e72144
DI 10.1371/journal.pone.0072144
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 205ER
UT WOS:000323425700139
PM 23977234
ER
PT J
AU Burke, LS
Hyland, PL
Pfeiffer, RM
Prescott, J
Wheeler, W
Mirabello, L
Savage, SA
Burdette, L
Yeager, M
Chanock, S
De Vivo, I
Tucker, MA
Goldstein, AM
Yang, XHR
AF Burke, Laura S.
Hyland, Paula L.
Pfeiffer, Ruth M.
Prescott, Jennifer
Wheeler, William
Mirabello, Lisa
Savage, Sharon A.
Burdette, Laurie
Yeager, Meredith
Chanock, Stephen
De Vivo, Immaculata
Tucker, Margaret A.
Goldstein, Alisa M.
Yang, Xiaohong R.
TI Telomere Length and the Risk of Cutaneous Malignant Melanoma in
Melanoma-Prone Families with and without CDKN2A Mutations
SO PLOS ONE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; OXIDATIVE STRESS; IN-VIVO; CANCER; LOCUS;
VARIANTS; EPIDEMIOLOGY; METAANALYSIS; INSTABILITY; P16(INK4A)
AB Introduction: Recent evidence suggests a link between constitutional telomere length (TL) and cancer risk. Previous studies have suggested that longer telomeres were associated with an increased risk of melanoma and larger size and number of nevi. The goal of this study was to examine whether TL modified the risk of melanoma in melanoma-prone families with and without CDKN2A germline mutations.
Materials and Methods: We measured TL in blood DNA in 119 cutaneous malignant melanoma (CMM) cases and 208 unaffected individuals. We also genotyped 13 tagging SNPs in TERT.
Results: We found that longer telomeres were associated with an increased risk of CMM (adjusted OR = 2.81, 95% CI = 1.02-7.72, P = 0.04). The association of longer TL with CMM risk was seen in CDKN2A- cases but not in CDKN2A+ cases. Among CMM cases, the presence of solar injury was associated with shorter telomeres (P = 0.002). One SNP in TERT, rs2735940, was significantly associated with TL (P = 0.002) after Bonferroni correction.
Discussion: Our findings suggest that TL regulation could be variable by CDKN2A mutation status, sun exposure, and pigmentation phenotype. Therefore, TL measurement alone may not be a good marker for predicting CMM risk.
C1 [Burke, Laura S.; Hyland, Paula L.; Pfeiffer, Ruth M.; Mirabello, Lisa; Savage, Sharon A.; Tucker, Margaret A.; Goldstein, Alisa M.; Yang, Xiaohong R.] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Rockville, MD USA.
[Hyland, Paula L.] NCI, Canc Prevent Fellowship Program, Off Directors, NIH,US Dept HHS, Rockville, MD USA.
[Prescott, Jennifer; De Vivo, Immaculata] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Prescott, Jennifer; De Vivo, Immaculata] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA.
[Prescott, Jennifer; De Vivo, Immaculata] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Prescott, Jennifer; De Vivo, Immaculata] Harvard Univ, Sch Med, Boston, MA USA.
[Wheeler, William] Informat Management Serv Inc, Rockville, MD USA.
[Burdette, Laurie; Yeager, Meredith; Chanock, Stephen] NCI, Core Genotyping Facil, SAIC Frederick Inc, Frederick, MD 21701 USA.
RP Yang, XHR (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Rockville, MD USA.
EM royang@mail.nih.gov
RI Tucker, Margaret/B-4297-2015; Savage, Sharon/B-9747-2015
OI Savage, Sharon/0000-0001-6006-0740
FU Cancer Prevention Fellowship Program; Center for Cancer Training,
National Cancer Institute, Bethesda, United States of America; Health
and Social Care, Northern Ireland, United Kingdom
FX Paula Hyland was funded by the Cancer Prevention Fellowship Program, the
Center for Cancer Training, National Cancer Institute, Bethesda, United
States of America and the Health and Social Care, Northern Ireland,
United Kingdom. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 39
TC 23
Z9 23
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 AUG 19
PY 2013
VL 8
IS 8
AR e71121
DI 10.1371/journal.pone.0071121
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 205ER
UT WOS:000323425700016
PM 23990928
ER
PT J
AU Hwang, IY
Park, C
Luong, T
Harrison, KA
Birnbaumer, L
Kehrl, JH
AF Hwang, Il-Young
Park, Chung
Luong, Thuyvi
Harrison, Kathleen A.
Birnbaumer, Lutz
Kehrl, John H.
TI The Loss of Gnai2 and Gnai3 in B Cells Eliminates B Lymphocyte
Compartments and Leads to a Hyper-IgM Like Syndrome
SO PLOS ONE
LA English
DT Article
ID CHEMOKINE RECEPTOR; BONE-MARROW; ADENYLYL-CYCLASE; GERMINAL CENTER;
ORGANIZATION; FOLLICLES; ORGANS; CXCR5; CCR7; MIGRATION
AB B lymphocytes are compartmentalized within lymphoid organs. The organization of these compartments depends upon signaling initiated by G-protein linked chemoattractant receptors. To address the importance of the G-proteins Ga-i2 and Ga-i3 in chemoattractant signaling we created mice lacking both proteins in their B lymphocytes. While bone marrow B cell development and egress is grossly intact; mucosal sites, splenic marginal zones, and lymph nodes essentially lack B cells. There is a partial block in splenic follicular B cell development and a 50-60% reduction in splenic B cells, yet normal numbers of splenic T cells. The absence of Ga-i2 and Ga-i3 in B cells profoundly disturbs the architecture of lymphoid organs with loss of B cell compartments in the spleen, thymus, lymph nodes, and gastrointestinal tract. This results in a severe disruption of B cell function and a hyper-IgM like syndrome. Beyond the pro-B cell stage, B cells are refractory to chemokine stimulation, and splenic B cells are poorly responsive to antigen receptor engagement. Ga-i2 and Ga-i3 are therefore critical for B cell chemoattractant receptor signaling and for normal B cell function. These mice provide a worst case scenario of the consequences of losing chemoattractant receptor signaling in B cells.
C1 [Hwang, Il-Young; Park, Chung; Luong, Thuyvi; Harrison, Kathleen A.; Kehrl, John H.] NIAID, Cell Mol Immunol Sect B, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Birnbaumer, Lutz] NIEHS, Neurobiol Lab, NIH, Dept Hlth & Human Serv, Durham, NC USA.
RP Kehrl, JH (reprint author), NIAID, Cell Mol Immunol Sect B, Immunoregulat Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM jkehrl@niaid.nih.gov
FU Intramural Research Program of the National Institutes of Health
[National Institute of Allergy and Infectious Diseases]; IRP project
[Z01-ES-101643]
FX This research was supported by the Intramural Research Program of the
National Institutes of Health [National Institute of Allergy and
Infectious Diseases] and IRP project Z01-ES-101643 (LB). The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 54
TC 6
Z9 6
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 AUG 19
PY 2013
VL 8
IS 8
AR UNSP e72596
DI 10.1371/journal.pone.0072596
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 205ER
UT WOS:000323425700178
PM 23977324
ER
PT J
AU Zhang, P
Maruyama, T
Konkel, JE
Abbatiello, B
Zamarron, B
Wang, ZQ
Chen, WJ
AF Zhang, Pin
Maruyama, Takashi
Konkel, Joanne E.
Abbatiello, Brittany
Zamarron, Brian
Wang, Zhao-qi
Chen, WanJun
TI PARP-1 Controls Immunosuppressive Function of Regulatory T Cells by
Destabilizing Foxp3
SO PLOS ONE
LA English
DT Article
ID POLY(ADP-RIBOSE) POLYMERASE GENE; IMMUNOLOGICAL SELF-TOLERANCE;
TRANSCRIPTION FACTOR FOXP3; MICE LACKING; ANTIGEN 4; TGF-BETA;
ACTIVATION; RESISTANT; PLAYS
AB Poly (ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme and transcription factor that is involved in inflammatory response, but its role in T cell response remains largely unknown. We show here that PARP-1 regulates the suppressive function of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs). Specifically, Tregs in mice with a null mutation of the PARP-1 gene (PARP-1(-/-)) showed significantly stronger suppressive activity than did wild-type Tregs in culture. We elucidate that this enhanced suppressive function is attributed to sustained higher expression of Foxp3 and CD25 in PARP-1(-/-) Tregs. Furthermore, in PARP-1(-/-) Tregs, Foxp3 protein shows substantially higher levels of binding to the conserved non-coding DNA sequence 2 (CNS2) at the foxp3 gene, a region important in maintaining Foxp3 gene expression in Tregs. Thus, our data reveal a role for PARP-1 in controlling the function of Tregs through modulation of the stable expression of Foxp3.
C1 [Zhang, Pin; Maruyama, Takashi; Konkel, Joanne E.; Abbatiello, Brittany; Zamarron, Brian; Chen, WanJun] Natl Inst Dent & Craniofacial Res, Mucosal Immunol Unit, OIIB, NIH, Bethesda, MD USA.
[Wang, Zhao-qi] Fritz Lipmann Inst eV, Leibniz Inst Age Res, D-07745 Jena, Germany.
RP Chen, WJ (reprint author), Natl Inst Dent & Craniofacial Res, Mucosal Immunol Unit, OIIB, NIH, Bethesda, MD USA.
EM wchen@dir.nidcr.nih.gov
OI Zamarron, Brian/0000-0001-6549-4230
FU Intramural Research Program of the National Institute of Dental and
Craniofacial Research of the National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institute of Dental and Craniofacial Research of 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 32
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 AUG 19
PY 2013
VL 8
IS 8
AR e71590
DI 10.1371/journal.pone.0071590
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 205ER
UT WOS:000323425700072
PM 23977081
ER
PT J
AU Klassen, MP
Yuan, Q
AF Klassen, Matthew P.
Yuan, Quan
TI Dendrite Plasticity: Branching Out for Greener Pastures
SO CURRENT BIOLOGY
LA English
DT Editorial Material
ID NEUROBIOLOGY; MECHANISMS; BRAIN
C1 [Klassen, Matthew P.] Univ Calif San Francisco, Howard Hughes Med Inst, Dept Physiol, San Francisco, CA 94158 USA.
[Yuan, Quan] NINDS, NIH, Bethesda, MD 20892 USA.
RP Klassen, MP (reprint author), Univ Calif San Francisco, Howard Hughes Med Inst, Dept Physiol, San Francisco, CA 94158 USA.
EM quan.yuan@nih.gov
FU Howard Hughes Medical Institute
NR 14
TC 1
Z9 1
U1 0
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0960-9822
J9 CURR BIOL
JI Curr. Biol.
PD AUG 19
PY 2013
VL 23
IS 16
BP R687
EP R688
DI 10.1016/j.cub.2013.07.036
PG 2
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 204WD
UT WOS:000323401100010
PM 23968924
ER
PT J
AU Putney, JW
AF Putney, James W., Jr.
TI Calcium Signaling: Septins Organize the SOC Channel
SO CURRENT BIOLOGY
LA English
DT Editorial Material
ID OPERATED CA2+ ENTRY; MOLECULAR-BASIS; CRAC CHANNEL; MICRODOMAINS;
INFLUX; SCREEN; ORAI1
C1 NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Putney, JW (reprint author), NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA.
EM putney@niehs.nih.gov
NR 14
TC 0
Z9 0
U1 0
U2 4
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0960-9822
J9 CURR BIOL
JI Curr. Biol.
PD AUG 19
PY 2013
VL 23
IS 16
BP R684
EP R685
DI 10.1016/j.cub.2013.07.042
PG 2
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 204WD
UT WOS:000323401100008
PM 23968922
ER
PT J
AU Dixit, D
Ghildiyal, R
Anto, NP
Ghosh, S
Sharma, V
Sen, E
AF Dixit, Deobrat
Ghildiyal, Ruchi
Anto, Nikhil Ponnor
Ghosh, Sourav
Sharma, Vivek
Sen, Ellora
TI Guggulsterone sensitizes glioblastoma cells to Sonic hedgehog inhibitor
SANT-1 induced apoptosis in a Ras/NF kappa B dependent manner
SO CANCER LETTERS
LA English
DT Article
DE Guggulsterone; NF kappa B; Ras; Shh; Glioblastoma
ID PANCREATIC-CANCER; GLIOMA-CELLS; IN-VIVO; FARNESYLTRANSFERASE INHIBITOR;
TRANSCRIPTIONAL ACTIVITY; MEDIATED APOPTOSIS; STAT3 ACTIVATION;
TUMOR-GROWTH; PATHWAY; EXPRESSION
AB Since Shh pathway effector, Gli1, is overexpressed in gliomas, we investigated the effect of novel Shh inhibitor SANT-1 on glioma cell viability. Though SANT-I failed to induce apoptosis, it reduced proliferation of glioma stem-like cells. Apart from canonical Shh cascade, Gli1 is also induced by non-canonical pathways including NF kappa B. Therefore, a combinatorial strategy with Ras/NF kappa B inhibitor, Guggulsterone, was employed to enhance effectiveness of SANT-1. Guggulsterone inhibited Ras and NF kappa B activity and sensitized cells to SANT-1 induced apoptosis via intrinsic apoptotic mechanism. Inhibition of either Ras or NF kappa B activity was sufficient to sensitize cells to SANT-1. Guggulsterone induced ERK activation also contributed to Caspase-9 activation. Since SANT-1 and Guggulsterone differentially target stem-like and non-stem glioma cells respectively, this combination warrants investigation as an effective anti-glioma therapy. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
C1 [Dixit, Deobrat; Ghildiyal, Ruchi; Anto, Nikhil Ponnor; Ghosh, Sourav; Sen, Ellora] Natl Brain Res Ctr, Manesar 122050, Haryana, India.
[Sharma, Vivek] NCI, NIH, Bethesda, MD 20896 USA.
RP Sen, E (reprint author), Natl Brain Res Ctr, Gurgaon 122050, Haryana, India.
EM ellora@nbrc.res.in
OI Dixit, Deobrat/0000-0003-4459-3904
FU Department of Biotechnology (DBT, Government of India)
[BT/PR/12924/Med/30/235/2009]; Council of Scientific and Industrial
Research (CSIR, Government of India)
FX The work was supported by a research Grant from the Department of
Biotechnology (DBT, Government of India #BT/PR/12924/Med/30/235/2009) to
ES. DD is supported by a research fellowship from Council of Scientific
and Industrial Research (CSIR, Government of India).
NR 56
TC 17
Z9 17
U1 0
U2 13
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3835
J9 CANCER LETT
JI Cancer Lett.
PD AUG 19
PY 2013
VL 336
IS 2
BP 347
EP 358
DI 10.1016/j.canlet.2013.03.025
PG 12
WC Oncology
SC Oncology
GA 187BB
UT WOS:000322089400012
PM 23548480
ER
PT J
AU Fagan, RL
Cryderman, DE
Kopelovich, L
Wallrath, LL
Brenner, C
AF Fagan, Rebecca L.
Cryderman, Diane E.
Kopelovich, Levy
Wallrath, Lori L.
Brenner, Charles
TI Laccaic Acid A Is a Direct, DNA-competitive Inhibitor of DNA
Methyltransferase 1
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID BREAST-CANCER CELLS; TUMOR-SUPPRESSOR GENES; TRANSCRIPTIONAL REGULATION;
EPIGENETIC REGULATION; ENZYMATIC-PROPERTIES; PPAR-GAMMA; METHYLATION;
DNMT1; MOUSE; EXPRESSION
AB Methylation of cytosines in CpG dinucleotides is the predominant epigenetic mark on vertebrate DNA. DNA methylation is associated with transcriptional repression. The pattern of DNA methylation changes during development and with disease. Human DNA methyltransferase 1 (Dnmt1), a 1616-amino acid multidomain enzyme, is essential for maintenance of DNA methylation in proliferating cells and is considered an important cancer drug target. Using a fluorogenic, endonuclease-coupled DNA methylation assay with an activated form of Dnmt1 engineered to lack the replication foci targeting sequence domain, we discovered that laccaic acid A (LCA), a highly substituted anthraquinone natural product, is a direct inhibitor with a 310 nM K-i. LCA is competitive with the DNA substrate in in vitro methylation assays and alters the expression of methylated genes in MCF-7 breast cancer cells synergistically with 5-aza-2'-deoxycytidine. LCA represents a novel class of Dnmt-targeted molecular probes, with biochemical properties that allow it to distinguish between non DNA-bound and DNA-bound Dnmt1.
C1 [Fagan, Rebecca L.; Cryderman, Diane E.; Wallrath, Lori L.; Brenner, Charles] Univ Iowa, Carver Coll Med, Dept Biochem, Iowa City, IA 52242 USA.
[Kopelovich, Levy] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Brenner, C (reprint author), Univ Iowa, Carver Coll Med, Dept Biochem, Iowa City, IA 52242 USA.
EM charles-brenner@uiowa.edu
RI Brenner, Charles/D-6339-2014
OI Brenner, Charles/0000-0002-4955-3226
FU National Institutes of Health [R01CA075954]; National Cancer Institute
[HHSN261200433000C]; Oberley Seed Grants from the University of Iowa
Holden Comprehensive Cancer Center; American Cancer Society postdoctoral
fellowship
FX This work was supported by National Institutes of Health Grant
R01CA075954, Contract HHSN261200433000C from the National Cancer
Institute and a generous gift from the Roy J. Carver Charitable Trust
(to C. B.). This work was also supported by Oberley Seed Grants from the
University of Iowa Holden Comprehensive Cancer Center (to C. B. and L.
L. W.), and an American Cancer Society postdoctoral fellowship (to R. L.
F.).
NR 59
TC 20
Z9 20
U1 0
U2 9
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 16
PY 2013
VL 288
IS 33
BP 23858
EP 23867
DI 10.1074/jbc.M113.480517
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 302NO
UT WOS:000330611400025
PM 23839987
ER
PT J
AU Subramanian, P
Locatelli-Hoops, S
Kenealey, J
DesJardin, J
Notari, L
Becerra, SP
AF Subramanian, Preeti
Locatelli-Hoops, Silvia
Kenealey, Jason
DesJardin, Jacqueline
Notari, Luigi
Becerra, S. Patricia
TI Pigment Epithelium-derived Factor (PEDF) Prevents Retinal Cell Death via
PEDF Receptor (PEDF-R) IDENTIFICATION OF A FUNCTIONAL LIGAND BINDING
SITE
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID ADIPOSE TRIGLYCERIDE LIPASE; POLYUNSATURATED FATTY-ACIDS; CEREBELLAR
GRANULE CELLS; DOCOSAHEXAENOIC ACID; OXIDATIVE STRESS; NEUROPROTECTIN
D1; PROSTATE-CANCER; FAMILY-MEMBERS; GENE-TRANSFER; IN-VITRO
AB The extracellular pigment epithelium-derived factor (PEDF) displays retina survival activity by interacting with receptor proteins on cell surfaces. We have previously reported that PEDF binds and stimulates PEDF receptor (PEDF-R), a transmembrane phospholipase. However, the PEDF binding site of PEDF-R and its involvement in survival activity have not been identified. The purpose of this work is to identify a biologically relevant ligand-binding site on PEDF-R. PEDF bound the PEDF-R ectodomain L4 (Leu(159)-Met(325)) with affinity similar to the full-length PEDF-R (Met(1)-Leu(504)). Binding assays using synthetic peptides spanning L4 showed that PEDF selectively bound E5b (Ile(193)-Leu(232)) and P1 (Thr(210)-Leu(249)) peptides. Recombinant C-terminal truncated PEDF-R4 (Met(1)-Leu(232)) and internally truncated PEDF-R and PEDF-R4 (Delta His(203)-Leu(232)) retained phospholipase activity of the full-length PEDF-R. However, PEDF-R polypeptides without the His(203)-Leu(232) region lost the PEDF affinity that stimulated their enzymatic activity. Cell surface labeling showed that PEDF-R is present in the plasma membranes of retina cells. Using siRNA to selectively knock down PEDF-R in retina cells, we demonstrated that PEDF-R is essential for PEDF-mediated cell survival and antiapoptotic activities. Furthermore, preincubation of PEDF with P1 and E5b peptides blocked the PEDF.PEDF-R-mediated retina cell survival activity, implying that peptide binding to PEDF excluded ligand-receptor interactions on the cell surface. Our findings establish that PEDF-R is required for the survival and antiapoptotic effects of PEDF on retina cells and has determinants for PEDF binding within its L4 ectodomain that are critical for enzymatic stimulation.
C1 [Subramanian, Preeti; Locatelli-Hoops, Silvia; Kenealey, Jason; DesJardin, Jacqueline; Notari, Luigi; Becerra, S. Patricia] NEI, Sect Prot Struct & Funct, Lab Retinal Cell & Mol Biol, NIH, Bethesda, MD 20892 USA.
RP Becerra, SP (reprint author), NEI, NIH, Bldg 6,Rm 134,6 Ctr Dr, Bethesda, MD 20892 USA.
EM becerrap@nei.nih.gov
FU National Institutes of Health, NEI, Intramural Research Program
FX This work was supported, in whole or in part, by the National Institutes
of Health, NEI, Intramural Research Program.
NR 64
TC 20
Z9 20
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 AUG 16
PY 2013
VL 288
IS 33
BP 23928
EP 23942
DI 10.1074/jbc.M113.487884
PG 15
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 302NO
UT WOS:000330611400032
PM 23818523
ER
PT J
AU Chen, ZG
Schiffman, M
Herrero, R
DeSalle, R
Anastos, K
Segondy, M
Sahasrabuddhe, VV
Gravitt, PE
Hsing, AW
Burk, RD
AF Chen, Zigui
Schiffman, Mark
Herrero, Rolando
DeSalle, Rob
Anastos, Kathryn
Segondy, Michel
Sahasrabuddhe, Vikrant V.
Gravitt, Patti E.
Hsing, Ann W.
Burk, Robert D.
TI Evolution and Taxonomic Classification of Alphapapillomavirus 7 Complete
Genomes: HPV18, HPV39, HPV45, HPV59, HPV68 and HPV70
SO PLOS ONE
LA English
DT Article
ID HUMAN-PAPILLOMAVIRUS TYPE-16; SQUAMOUS INTRAEPITHELIAL LESIONS; GENITAL
HUMAN-PAPILLOMAVIRUS; GRADE CERVICAL LESIONS; NEUTRALIZING ANTIBODIES;
MAXIMUM-LIKELIHOOD; SEQUENCE-ANALYSIS; VARIANT LINEAGES; MIXED MODELS;
CANCER
AB Background: The species Alphapapillomavirus 7 (alpha-7) contains human papillomavirus genotypes that account for 15% of invasive cervical cancers and are disproportionately associated with adenocarcinoma of the cervix. Complete genome analyses enable identification and nomenclature of variant lineages and sublineages.
Methods: The URR/E6 region was sequenced to screen for novel variants of HPV18, 39, 45, 59, 68, 70, 85 and 97 from 1147 cervical samples obtained from multiple geographic regions that had previously been shown to contain an alpha-7 HPV isolate. To study viral heterogeneity, the complete 8 kb genome of 128 isolates, including 109 sequenced for this analysis, were annotated and analyzed. Viral evolution was characterized by constructing phylogenic trees using maximum-likelihood and Bayesian algorithms. Global and pairwise alignments were used to calculate total and ORF/region nucleotide differences; lineages and sublineages were assigned using an alphanumeric system. The prototype genome was assigned to the A lineage or A1 sublineage.
Results: The genomic diversity of alpha-7 HPV types ranged from 1.1% to 6.7% nucleotide sequence differences; the extent of genome-genome pairwise intratype heterogeneity was 1.1% for HPV39, 1.3% for HPV59, 1.5% for HPV45, 1.6% for HPV70, 2.1% for HPV18, and 6.7% for HPV68. ME180 (previously a subtype of HPV68) was designated as the representative genome for HPV68 sublineage C1. Each ORF/region differed in sequence diversity, from most variable to least variable: noncoding region 1 (NCR1) / noncoding region 2 (NCR2) > upstream regulatory region (URR) > E6 / E7 > E2 / L2 > E1 / L1.
Conclusions: These data provide estimates of the maximum viral genomic heterogeneity of alpha-7 HPV type variants. The proposed taxonomic system facilitates the comparison of variants across epidemiological and molecular studies. Sequence diversity, geographic distribution and phylogenetic topology of this clinically important group of HPVs suggest an independent evolutionary history for each type.
C1 [Chen, Zigui; Burk, Robert D.] Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA.
[Schiffman, Mark; Sahasrabuddhe, Vikrant V.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Herrero, Rolando] Fdn INCIENSA, San Jose, Costa Rica.
[DeSalle, Rob] Amer Museum Nat Hist, Sackler Inst Comparat Genom, New York, NY 10024 USA.
[Anastos, Kathryn] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA.
[Anastos, Kathryn] Montefiore Med Ctr, Bronx, NY 10467 USA.
[Anastos, Kathryn; Burk, Robert D.] Albert Einstein Coll Med, Dept Epidemiol & Publ Hlth, Bronx, NY 10467 USA.
[Anastos, Kathryn; Burk, Robert D.] Albert Einstein Coll Med, Dept Obstet, Bronx, NY 10467 USA.
[Segondy, Michel] Montpellier Univ Hosp, Dept Biol & Pathol, Montpellier, France.
[Sahasrabuddhe, Vikrant V.] Vanderbilt Univ, Inst Global Hlth, Nashville, TN 37235 USA.
[Gravitt, Patti E.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Hsing, Ann W.] Canc Prevent Inst Calif, Fremont, CA USA.
[Burk, Robert D.] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA.
RP Burk, RD (reprint author), Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA.
EM robert.burk@einstein.yu.edu
RI Chen, Zigui/E-8490-2017
FU National Cancer Institute [CA78527]; Einstein-Montefiore Center for
AIDS; National Institutes of Health [AI-51519]; Einstein Cancer Research
Center from the National Cancer Institute [P30CA013330]
FX This work was supported in part by the National Cancer Institute
(CA78527), the Einstein-Montefiore Center for AIDS funded by the
National Institutes of Health (AI-51519) and the Einstein Cancer
Research Center (P30CA013330) from the National Cancer Institute. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 57
TC 16
Z9 16
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 AUG 16
PY 2013
VL 8
IS 8
AR e72565
DI 10.1371/journal.pone.0072565
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 207BA
UT WOS:000323570200075
PM 23977318
ER
PT J
AU McPherron, AC
AF McPherron, Alexandra C.
TI Through Thick and Thin: A Circulating Growth Factor Inhibits Age-Related
Cardiac Hypertrophy
SO CIRCULATION RESEARCH
LA English
DT Editorial Material
ID GROWTH/DIFFERENTIATION FACTOR 11; LEFT-VENTRICULAR MASS; HEART-FAILURE;
MUSCLE MASS; MYOSTATIN EXPRESSION; SKELETAL-MUSCLE; NEGATIVE REGULATOR;
BETA SUPERFAMILY; GDF11; MICE
C1 NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
RP McPherron, AC (reprint author), NIDDK, Genet Dev & Dis Branch, NIH, Bldg 10,Room 8D12A,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM mcpherrona@niddk.nih.gov
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases, National Institutes of Health
FX Dr McPherron is supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health.
NR 50
TC 3
Z9 3
U1 1
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7330
EI 1524-4571
J9 CIRC RES
JI Circ.Res.
PD AUG 16
PY 2013
VL 113
IS 5
BP 487
EP 491
DI 10.1161/CIRCRESAHA.113.302239
PG 5
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA 203VR
UT WOS:000323322600006
PM 23948581
ER
PT J
AU Jaffe, H
Patterson, AP
Lurie, N
AF Jaffe, Harold
Patterson, Amy P.
Lurie, Nicole
TI Extra Oversight for H7N9 Experiments
SO SCIENCE
LA English
DT Letter
C1 [Jaffe, Harold] Ctr Dis Control & Prevent, Atlanta, GA 30329 USA.
[Patterson, Amy P.] NIH, Bethesda, MD 20852 USA.
[Lurie, Nicole] Dept Hlth & Human Serv, Washington, DC 20201 USA.
RP Patterson, AP (reprint author), NIH, Bethesda, MD 20852 USA.
EM pattersa@od.nih.gov
NR 3
TC 1
Z9 1
U1 1
U2 16
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD AUG 16
PY 2013
VL 341
IS 6147
BP 713
EP 714
DI 10.1126/science.1244158
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 201DZ
UT WOS:000323122200017
PM 23926189
ER
PT J
AU Kamel, F
AF Kamel, Freya
TI Paths from Pesticides to Parkinson's
SO SCIENCE
LA English
DT Editorial Material
ID DISEASE; EXPOSURE; RISK; SERUM
C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
RP Kamel, F (reprint author), NIEHS, Epidemiol Branch, POB 12233, Res Triangle Pk, NC 27709 USA.
EM kamel@niehs.nih.gov
OI Kamel, Freya/0000-0001-5052-6615
FU Intramural NIH HHS
NR 18
TC 36
Z9 36
U1 4
U2 43
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD AUG 16
PY 2013
VL 341
IS 6147
BP 722
EP 723
DI 10.1126/science.1243619
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 201DZ
UT WOS:000323122200027
PM 23950519
ER
PT J
AU Gamaldo, CE
Gamaldo, A
Creighton, J
Salas, RE
Selnes, OA
David, PM
Mbeo, G
Parker, BS
Brown, A
McArthur, JC
Smith, MT
AF Gamaldo, Charlene E.
Gamaldo, Alyssa
Creighton, Jason
Salas, Rachel E.
Selnes, Ola A.
David, Paula M.
Mbeo, Gilbert
Parker, Benjamin S.
Brown, Amanda
McArthur, Justin C.
Smith, Michael T.
TI Evaluating Sleep and Cognition in HIV
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE HIV; sleep; sleep disorders; cognition; quality of life
ID NECROSIS-FACTOR-ALPHA; BLOOD-BRAIN-BARRIER; NEUROCOGNITIVE DISORDERS;
ANTIRETROVIRAL THERAPY; CIRCADIAN-RHYTHM; NORMATIVE DATA; EFAVIRENZ;
INFECTION; DEPRIVATION; PREVALENCE
AB Objective: To examine the relationship between measures of sleep quality and cognitive performance in HIV-positive individuals stable on combination antiretroviral therapy.
Design: Multimethod assessments of sleep quality, patterns, and cognitive performance were assessed in a predominantly black HIV-positive cohort.
Methods: Sleep quality and patterns were characterized in 36 subjects by polysomnogram, 2-week actigraphy monitoring, and validated sleep questionnaires. Cognitive performance was assessed with a battery of neuropsychological tests.
Results: The majority of participants were cognitively impaired [based on Frascati (75%) criteria]. Self-reported mean scores on the Pittsburgh sleep quality index and the insomnia severity scale suggested poor sleep quality. Better cognitive performance, particularly on tasks of attention, frontal/executive function, and psychomotor/motor speed, was associated with polysomnogram sleep indices (ie, reduced wake after sleep onset, greater sleep efficiency, greater sleep latency, and greater total sleep time). Thirty-seven percent of participants had sleep patterns suggestive of chronic partial sleep deprivation, which was associated with significantly worse performance on the digit symbol test (P = 0.006), nondominant pegboard (P = 0.043), and verbal fluency tests (P = 0.044).
Conclusions: Our results suggest that compromised sleep quality and duration may have a significant impact on cognitive performance in HIV-positive individuals. Future studies are warranted to determine the utility of sleep quality and quantity indices as potential predictive biomarkers for development and progression of future HIV-associated neurocognitive disorder.
C1 [Gamaldo, Charlene E.; Creighton, Jason; Salas, Rachel E.; Selnes, Ola A.; David, Paula M.; Mbeo, Gilbert; Parker, Benjamin S.; Brown, Amanda; McArthur, Justin C.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA.
[Gamaldo, Alyssa] NIA, Lab Behav Neurosci, Baltimore, MD 21224 USA.
[McArthur, Justin C.] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA.
[McArthur, Justin C.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
[McArthur, Justin C.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA.
[Smith, Michael T.] Johns Hopkins Univ, Dept Psychiat & Behav Med, Baltimore, MD USA.
RP Gamaldo, CE (reprint author), Johns Hopkins Univ Hosp, 600 N Wolfe St,Meyer 6-119, Baltimore, MD 21287 USA.
EM cgamald1@jhmi.edu
FU National Center for Research Resources (NCRR) [UL1 RR 025005]; NIH
Roadmap for Medical Research; National Institute of Mental Health (NIMH)
[5P30MH075673-S02]; JHU NIMH Center for Novel Therapeutics of HIV; JHU
Center for Mind-Body Research; NIMH; Central Nervous System HIV
Antiretroviral Therapy Effects Research (CHARTER); National Center for
Research Resources; National Center for Advancing Translational
Sciences, National Institutes of Health [UL1 RR 025005]
FX Supported by grant number UL1 RR 025005 from the National Center for
Research Resources (NCRR), a component of the National Institutes of
Health (NIH), and NIH Roadmap for Medical Research. This study was also
supported by award 5P30MH075673-S02 from the National Institute of
Mental Health (NIMH) (principal investigator, J.C.M.), a Developmental
Grant from JHU NIMH Center for Novel Therapeutics of HIV-associated
Cognitive Disorders (to author C. E. G., principal investigator,
J.C.M.), and a Developmental Grant from JHU Center for Mind-Body
Research (PI Jennifer Haythornthwaite PI to author C. E. G.). The
recruitment of participants was assisted by an existing cohort, funded
by NIMH, the Central Nervous System HIV Antiretroviral Therapy Effects
Research (CHARTER). The project described was supported by the National
Center for Research Resources and the National Center for Advancing
Translational Sciences, National Institutes of Health, through Grant UL1
RR 025005.
NR 61
TC 10
Z9 10
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD AUG 15
PY 2013
VL 63
IS 5
BP 609
EP 616
PG 8
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 300FN
UT WOS:000330449900020
PM 23722610
ER
PT J
AU Thompson, IM
Goodman, PJ
Tangen, CM
Parnes, HL
Minasian, LM
Godley, PA
Lucia, MS
Ford, LG
AF Thompson, Ian M., Jr.
Goodman, Phyllis J.
Tangen, Catherine M.
Parnes, Howard L.
Minasian, Lori M.
Godley, Paul A.
Lucia, M. Scott
Ford, Leslie G.
TI Long-Term Survival of Participants in the Prostate Cancer Prevention
Trial
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID 5-ALPHA-REDUCTASE INHIBITORS; FOLLOW-UP; FINASTERIDE; SENSITIVITY
AB BackgroundIn the Prostate Cancer Prevention Trial (PCPT), finasteride significantly reduced the risk of prostate cancer but was associated with an increased risk of high-grade disease. With up to 18 years of follow-up, we analyzed rates of survival among all study participants and among those with prostate cancer.
MethodsWe collected data on the incidence of prostate cancer among PCPT participants for an additional year after our first report was published in 2003 and searched the Social Security Death Index to assess survival status through October 31, 2011.
ResultsAmong 18,880 eligible men who underwent randomization, prostate cancer was diagnosed in 989 of 9423 (10.5%) in the finasteride group and 1412 of 9457 (14.9%) in the placebo group (relative risk in the finasteride group, 0.70; 95% confidence interval [CI], 0.65 to 0.76; P<0.001). Of the men who were evaluated, 333 (3.5%) in the finasteride group and 286 (3.0%) in the placebo group had high-grade cancer (Gleason score, 7 to 10) (relative risk, 1.17; 95% CI, 1.00 to 1.37; P=0.05). Of the men who died, 2538 were in the finasteride group and 2496 were in the placebo group, for 15-year survival rates of 78.0% and 78.2%, respectively. The unadjusted hazard ratio for death in the finasteride group was 1.02 (95% CI, 0.97 to 1.08; P=0.46). Ten-year survival rates were 83.0% in the finasteride group and 80.9% in the placebo group for men with low-grade prostate cancer and 73.0% and 73.6%, respectively, for those with high-grade prostate cancer.
ConclusionsFinasteride reduced the risk of prostate cancer by about one third. High-grade prostate cancer was more common in the finasteride group than in the placebo group, but after 18 years of follow-up, there was no significant between-group difference in the rates of overall survival or survival after the diagnosis of prostate cancer. (Funded by the National Cancer Institute.)
The use of finasteride to prevent prostate cancer reduced the risk of low-grade tumors by 43%, as compared with placebo. High-grade tumors were more common in the finasteride group, but long-term follow-up did not show a significant between-group difference in survival. With the advent of prostate-specific antigen (PSA) testing in the late 1980s, the rate of diagnosis of prostate cancer rose dramatically. Currently, a man in the United States has a 16.5% lifetime risk of receiving a diagnosis of prostate cancer.(1) The timing and magnitude of the 44% reduction in prostate-cancer mortality after the widespread adoption of PSA testing suggest that both screening and treatment improvements have contributed to this decline.(2) Unfortunately, treatments for prostate cancer (radiation and surgery) are associated with a substantial risk of side effects, including sexual, urinary, and bowel complications, that can dramatically affect quality of life. ...
C1 [Thompson, Ian M., Jr.] Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA.
[Goodman, Phyllis J.; Tangen, Catherine M.] SW Oncol Grp, Ctr Stat, Seattle, WA USA.
[Goodman, Phyllis J.; Tangen, Catherine M.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Parnes, Howard L.; Minasian, Lori M.; Ford, Leslie G.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Godley, Paul A.] Univ N Carolina, Sch Med, Div Hematol Oncol, Sch Publ Hlth, Chapel Hill, NC USA.
[Godley, Paul A.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Lucia, M. Scott] Univ Colorado, Denver Sch Med, Dept Pathol, Denver, CO 80202 USA.
RP Thompson, IM (reprint author), Canc Therapy & Res Ctr S Texas, Suite U627,7979 Wurzbach Rd, San Antonio, TX 78229 USA.
EM thompsoni@uthscsa.edu
FU Public Health Service grant from Division of Cancer Prevention, National
Cancer Institute [CA37429]; Ferring; Amgen; Eli Lilly
FX Supported by a Public Health Service grant (CA37429) from the Division
of Cancer Prevention, National Cancer Institute. Dr. Thompson reports
receiving consulting fees from Ferring and being a named inventor on
patent applications filed by his institution for a penile-prosthesis
design for the management of erectile dysfunction and for a
lab-on-a-chip procedure for point-of-service identification of
biomarkers for prostate-cancer detection; and Dr. Tangen, receiving
consulting fees from Amgen and Eli Lilly. No other potential conflict of
interest relevant to this article was reported.
NR 21
TC 75
Z9 76
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 AUG 15
PY 2013
VL 369
IS 7
BP 603
EP 610
DI 10.1056/NEJMoa1215932
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 243YO
UT WOS:000326354500006
PM 23944298
ER
PT J
AU Ghany, MG
Liang, TJ
AF Ghany, Marc G.
Liang, T. Jake
TI Current and Future Therapies for Hepatitis C Virus Infection REPLY
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 [Ghany, Marc G.; Liang, T. Jake] NIH, Bethesda, MD 20892 USA.
RP Ghany, MG (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
EM jliang@nih.gov
FU Intramural NIH HHS [Z99 DK999999, ZIA DK054505-16, ZIA DK054504-17, ZIA
DK054503-16, ZIA DK054505-17, ZIA DK054504-16, ZIA DK054503-17]
NR 4
TC 17
Z9 18
U1 2
U2 3
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 AUG 15
PY 2013
VL 369
IS 7
BP 679
EP 680
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 243YO
UT WOS:000326354500028
PM 23944318
ER
PT J
AU Kopelovich, L
Herbert, BS
AF Kopelovich, Levy
Herbert, Brittney-Shea
TI Heritable one-hit events defining cancer prevention?
SO CELL CYCLE
LA English
DT Article
DE cancer prevention; cancer syndromes; Knudson; two-hit; one-hit; driver
mutations; passenger mutations
ID ALTERED GENE-EXPRESSION; SKIN FIBROBLASTS; BREAST-CANCER; FAMILIAL
SYNDROME; MUTATIONS; P53; CELLS; SUSCEPTIBILITY; MELANOMA; CARRIERS
AB Over 100 y ago (1902-1914) Theodor Boveri suggested a role for mutations in cancer.(1,2) Boveri's ideas were derived from the then just-emerging chromosome theory of inheritance. While demonstrating chromosomal aberrations as a cause of genetic imbalance, Boveri suggested that possible causes of malignancy may include events such as aneuploidy that are now defined as gene mutations, asserting all the while that malignancy occurs at the cellular level. Indeed, studies to date essentially uniformly show that cancer is a genetic disease.(3,415 years of age with AS were studied at necropsy over a 50-year period by the same investigator. Of the 260 patients, the valve in 37 (14%) was congenitally unicuspid, in 123 (47%), congenitally bicuspid, and in 100 (38%), tricuspid. Aortic valve structure varied with age of death (in years; unicuspid 52 +/- 17, bicuspid 63 +/- 12, and tricuspid 70 +/- 14 years); gender (men/women: unicuspid 95%/5%, bicuspid 78%/22%, and tricuspid 63%/37%), and frequency of calcium in the mitral valve annulus and epicardial coronary arteries. The patients with cardiac-related symptoms compared with those without were more likely to have a congenitally malformed valve (unicuspid 17% vs 12%; bicuspid 51% vs 29%; tricuspid 31% vs 60%; unadjusted p = 0.013), to die from cardiac disease (86% vs 54%; unadjusted p = 0.001), and to have larger hearts (mean cardiac weight 606 +/- 138 g vs 523 +/- 121 g; unadjusted p = 0.009) and a larger quantity of calcium in the aortic valve cusps. In conclusion, the length of survival in adults with AS is related to valve structure, gender, presence of cardiac-related symptoms, cardiac mass, and quantity of calcium in the aortic valve cusps. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Roberts, William C.; Vowels, Travis J.; Ko, Jong M.] Baylor Univ, Med Ctr, Baylor Heart & Vasc Inst, Dallas, TX USA.
[Roberts, William C.] Baylor Univ, Med Ctr, Div Cardiol, Dept Internal Med, Dallas, TX USA.
[Roberts, William C.] Baylor Univ, Med Ctr, Dept Pathol, Dallas, TX USA.
[Roberts, William C.; Mathur, Raj P.; Shirani, Jamshid] NHLBI, Pathol Branch, NIH, Bethesda, MD 20892 USA.
[Filardo, Giovanni] Baylor Univ, Med Ctr, Inst Hlth Care Res & Improvement, Dallas, TX USA.
[Filardo, Giovanni] So Methodist Univ, Dept Stat Sci, Dallas, TX 75275 USA.
RP Roberts, WC (reprint author), Baylor Univ, Med Ctr, Baylor Heart & Vasc Inst, Dallas, TX USA.
EM wc.roberts@baylorhealth.edu
FU Baylor Heart and Vascular Institute Cardiovascular Research Review
Committee; Baylor Health Care System Foundation
FX This work was supported by grants from the Baylor Heart and Vascular
Institute Cardiovascular Research Review Committee and Baylor Health
Care System Foundation.
NR 21
TC 7
Z9 7
U1 0
U2 2
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD AUG 15
PY 2013
VL 112
IS 4
BP 541
EP 553
DI 10.1016/j.amjcard.2013.04.020
PG 13
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 204YR
UT WOS:000323407700015
PM 23726174
ER
PT J
AU Zarate, CA
Mathews, D
Ibrahim, L
Chaves, JF
Marquardt, C
Ukoh, I
Jolkovsky, L
Brutsche, NE
Smith, MA
Luckenbaugh, DA
AF Zarate, Carlos A., Jr.
Mathews, Daniel
Ibrahim, Lobna
Chaves, Jose Franco
Marquardt, Craig
Ukoh, Immaculata
Jolkovsky, Libby
Brutsche, Nancy E.
Smith, Mark A.
Luckenbaugh, David A.
TI A Randomized Trial of a Low-Trapping Nonselective N-Methyl-D-Aspartate
Channel Blocker in Major Depression
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Antidepressant; depression; glutamate; low-trapping NMDA; rapid-acting;
treatment-resistant
ID NMDA RECEPTOR ANTAGONISTS; ENDOTHELIAL GROWTH-FACTOR; ADD-ON TRIAL;
RATING-SCALE; LOW-AFFINITY; BIPOLAR DEPRESSION; ANTIDEPRESSANT;
DISORDER; KETAMINE; STATES
AB Background: The high-affinity N-methyl-D-aspartate (NMDA) antagonist ketamine exerts rapid antidepressant effects but has psychotomimetic properties. AZD6765 is a low-trapping NMDA channel blocker with low rates of associated psychotomimetic effects. This study investigated whether AZD6765 could produce rapid antidepressant effects in subjects with treatment-resistant major depressive disorder (MDD).
Methods: In this double-blind, randomized, crossover, placebo-controlled study, 22 subjects with DSM-IV treatment-resistant MDD received a single infusion of either AZD6765 (150 mg) or placebo on 2 test days 1 week apart. The primary outcome measure was the Montgomery-Asberg Depression Rating Scale, which was used to rate overall depressive symptoms at baseline and 60, 80, 110, and 230 min postinfusion and on Days 1, 2, 3, and 7 postinfusion. Several secondary outcome measures were also used, including the Hamilton Depression Rating Scale.
Results: Within 80 min, Montgomery-Asberg Depression Rating Scale scores significantly improved in subjects receiving AZD6765 compared with placebo; this improvement remained significant only through 110 min (d=.40). On the Hamilton Depression Rating Scale, a drug difference was found at 80 and 110 min and at Day 2 (d=.49). Overall, 32% of subjects responded to AZD6765, and 15% responded to placebo at some point during the trial. No difference was observed between the groups with regard to psychotomimetic or dissociative adverse effects.
Conclusions: In patients with treatment-resistant MDD, a single intravenous dose of the low-trapping NMDA channel blocker AZD6765 was associated with rapid but short-lived antidepressant effects; no psychotomimetic effects were observed.
C1 [Zarate, Carlos A., Jr.; Mathews, Daniel; Ibrahim, Lobna; Chaves, Jose Franco; Marquardt, Craig; Ukoh, Immaculata; Jolkovsky, Libby; Brutsche, Nancy E.; Luckenbaugh, David A.] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20892 USA.
US Dept HHS, Bethesda, MD USA.
[Smith, Mark A.] AstraZeneca, Wilmington, DE USA.
RP Zarate, CA (reprint author), NIMH, NIH, CRC, 10 Ctr Dr,Unit 7 Southeast,Room 7-3445, Bethesda, MD 20892 USA.
EM zaratec@mail.nih.gov
FU Intramural Research Program at the National Institute of Mental Health,
National Institutes of Health, and Department of Health Human Services
FX Funding for this work was supported by the Intramural Research Program
at the National Institute of Mental Health, National Institutes of
Health, and Department of Health & Human Services.
NR 46
TC 77
Z9 78
U1 3
U2 25
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD AUG 15
PY 2013
VL 74
IS 4
BP 257
EP 264
DI 10.1016/j.biopsych.2012.10.019
PG 8
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 201PY
UT WOS:000323156100006
PM 23206319
ER
PT J
AU Hardee, JE
Benson, BE
Bar-Haim, Y
Mogg, K
Bradley, BP
Chen, G
Britton, JC
Ernst, M
Fox, NA
Pine, DS
Perez-Edgar, K
AF Hardee, Jillian E.
Benson, Brenda E.
Bar-Haim, Yair
Mogg, Karin
Bradley, Brendan P.
Chen, Gang
Britton, Jennifer C.
Ernst, Monique
Fox, Nathan A.
Pine, Daniel S.
Perez-Edgar, Koraly
TI Patterns of Neural Connectivity During an Attention Bias Task Moderate
Associations Between Early Childhood Temperament and Internalizing
Symptoms in Young Adulthood
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Attention bias; functional connectivity; Granger causality; imaging;
internalizing problems; temperament
ID GENERALIZED ANXIETY DISORDER; BEHAVIORALLY INHIBITED ADOLESCENTS;
ANTERIOR CINGULATE ACTIVATION; PREFRONTAL CORTEX ACTIVATION; SOCIAL
ANXIETY; TRAIT ANXIETY; ANGRY FACES; IMPLICIT REGULATION; PEDIATRIC
ANXIETY; CHILDREN
AB Background: Biased attention to threat is found in both individuals with anxiety symptoms and children with the childhood temperament of behavioral inhibition (BI). Although perturbed fronto-amygdala function is implicated in biased attention among anxious individuals, no work has examined the neural correlates of attention biases in BI. Work in this area might clarify underlying mechanisms for anxiety in a sample at risk for internalizing disorders. We examined the relations among early childhood BI, fronto-amygdala connectivity during an attention bias task in young adulthood, and internalizing symptoms, assessed in young adulthood.
Methods: Children were assessed for BI at multiple age points from infancy through age seven. On the basis of a composite of observational and maternal report data, we selected 21 young adults classified as having a history of BI and 23 classified as non-BI for this study (n = 44). Participants completed an event-related functional magnetic resonance imaging attention-bias task involving threat (angry faces) and neutral trials. Internalizing symptoms were assessed by self-report and diagnostic interviews.
Results: The young adults characterized in childhood with BI exhibited greater strength in threat-related connectivity than non-behaviorally inhibited young adults. Between-group differences manifested in connections between the amygdala and two frontal regions: dorsolateral prefrontal cortex and anterior insula. Amygdala-insula connectivity also interacted with childhood BI to predict young adult internalizing symptoms.
Conclusions: Behavioral inhibition during early childhood predicts differences as young adults in threat and attention-related fronto-amygdala connectivity. Connectivity strength, in turn, moderated the relations between early BI and later psychopathology.
C1 [Hardee, Jillian E.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA.
[Benson, Brenda E.; Ernst, Monique; Pine, Daniel S.] NIMH, Sect Dev & Affect Neurosci, Bethesda, MD 20892 USA.
[Chen, Gang] NIMH, Sci & Stat Comp Core, Bethesda, MD 20892 USA.
[Fox, Nathan A.] Univ Maryland, Dept Human Dev & Quantitat Methodol, College Pk, MD 20742 USA.
[Bar-Haim, Yair] Tel Aviv Univ, Sch Psychol Sci, IL-69978 Tel Aviv, Israel.
[Mogg, Karin; Bradley, Brendan P.] Univ Southampton, Sch Psychol, Southampton, Hants, England.
[Britton, Jennifer C.] Univ Miami, Dept Psychol, Coral Gables, FL 33124 USA.
[Perez-Edgar, Koraly] Penn State Univ, Dept Psychol, University Pk, PA 16802 USA.
[Perez-Edgar, Koraly] Penn State Univ, Ctr Child Study, University Pk, PA 16802 USA.
RP Perez-Edgar, K (reprint author), Penn State Univ, Dept Psychol, Ctr Child Study, 111 Moore Bldg,USB 1,Room 101G, University Pk, PA 16802 USA.
EM kxp24@psu.edu
RI Britton, Jennifer/J-4501-2013; Mogg, Karin/C-1181-2008; Bradley,
Brendan/B-9724-2008;
OI Mogg, Karin/0000-0002-2738-7378; Bradley, Brendan/0000-0003-2801-4271;
Perez-Edgar, Koraly/0000-0003-4051-9563; Hardee,
Jillian/0000-0001-8230-3045
FU Intramural Research Program of the National Institutes of Health;
National Institutes of Health [MH073569, MH094633, MH074454,
R37HD17899]; Brain and Behavior Research Foundation
FX Funding was provided by the Intramural Research Program of the National
Institutes of Health, grants from the National Institutes of Health to
KPE (MH073569 and MH094633) and NAF (MH074454; R37HD17899), as well as
from the Brain and Behavior Research Foundation (Distinguished
Investigator Award) to NAF. We would like to thank the participants and
families for their continued involvement in our study.
NR 58
TC 30
Z9 30
U1 7
U2 32
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD AUG 15
PY 2013
VL 74
IS 4
BP 273
EP 279
DI 10.1016/j.biopsych.2013.01.036
PG 7
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 201PY
UT WOS:000323156100008
PM 23489415
ER
PT J
AU Aravind, L
Anand, S
Iyer, LM
AF Aravind, L.
Anand, Swadha
Iyer, Lakshminarayan M.
TI Novel autoproteolytic and DNA-damage sensing components in the bacterial
SOS response and oxidized methylcytosine-induced eukaryotic DNA
demethylation systems
SO BIOLOGY DIRECT
LA English
DT Article
ID ESCHERICHIA-COLI; POLYMERASE-IV; MUTAGENESIS; DATABASE; PROTEIN;
5-CARBOXYLCYTOSINE; REPLICATION; PREDICTION; INDUCTION; EXCISION
AB The bacterial SOS response is an elaborate program for DNA repair, cell cycle regulation and adaptive mutagenesis under stress conditions. Using sensitive sequence and structure analysis, combined with contextual information derived from comparative genomics and domain architectures, we identify two novel domain superfamilies in the SOS response system. We present evidence that one of these, the SOS response associated peptidase (SRAP; Pfam: DUF159) is a novel thiol autopeptidase. Given the involvement of other autopeptidases, such as LexA and UmuD, in the SOS response, this finding suggests that multiple structurally unrelated peptidases have been recruited to this process. The second of these, the ImuB-C superfamily, is linked to the Y-family DNA polymerase-related domain in ImuB, and also occurs as a standalone protein. We present evidence using gene neighborhood analysis that both these domains function with different mutagenic polymerases in bacteria, such as Pol IV (DinB), Pol V (UmuCD) and ImuA-ImuB-DnaE2 and also other repair systems, which either deploy Ku and an ATP-dependent ligase or a SplB-like radical SAM photolyase. We suggest that the SRAP superfamily domain functions as a DNA-associated autoproteolytic switch that recruits diverse repair enzymes upon DNA damage, whereas the ImuB-C domain performs a similar function albeit in a non-catalytic fashion. We propose that C3Orf37, the eukaryotic member of the SRAP superfamily, which has been recently shown to specifically bind DNA with 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxycytosine, is a sensor for these oxidized bases generated by the TET enzymes from methylcytosine. Hence, its autoproteolytic activity might help it act as a switch that recruits DNA repair enzymes to remove these oxidized methylcytosine species as part of the DNA demethylation pathway downstream of the TET enzymes.
C1 [Aravind, L.; Anand, Swadha; Iyer, Lakshminarayan M.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Aravind, L (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM aravind@ncbi.nlm.nih.gov
FU US Department of Health and Human Services (National Library of
Medicine, NIH)
FX The authors' research is supported by the intramural funds of the US
Department of Health and Human Services (National Library of Medicine,
NIH).
NR 29
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U1 0
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1745-6150
J9 BIOL DIRECT
JI Biol. Direct
PD AUG 15
PY 2013
VL 8
AR 20
DI 10.1186/1745-6150-8-20
PG 11
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 207DI
UT WOS:000323577100001
PM 23945014
ER
PT J
AU Horning, SJ
Haber, DA
Selig, WKD
Ivy, SP
Roberts, SA
Allen, JD
Sigal, EV
Sawyers, CL
AF Horning, Sandra J.
Haber, Daniel A.
Selig, Wendy K. D.
Ivy, S. Percy
Roberts, Samantha A.
Allen, Jeff D.
Sigal, Ellen V.
Sawyers, Charles L.
TI Developing Standards for Breakthrough Therapy Designation in Oncology
SO CLINICAL CANCER RESEARCH
LA English
DT Article
AB In July 2012, Congress passed the Food and Drug Administration Safety and Innovation Act (FDASIA). The Advancing Breakthrough Therapies for Patients Act was incorporated into a Title of FDASIA to expedite clinical development of new, potential "breakthrough" drugs or treatments that show dramatic responses in early-phase studies. Using this regulatory pathway, once a promising new drug candidate is designated as a "Breakthrough Therapy", the U. S. Food and Drug Administration (FDA) and sponsor would collaborate to determine the best path forward to abbreviate the traditional three-phase approach to drug development. The breakthrough legislation requires that an FDA guidance be drafted that details specific requirements of the bill to aid FDA in implementing requirements of the Act. In this article, we have proposed criteria to define a product as a Breakthrough Therapy, and discussed critical components of the development process that would require flexibility in order to enable expedited development of a Breakthrough Therapy. (C)2013 AACR.
C1 [Horning, Sandra J.] Genentech Inc, San Francisco, CA 94080 USA.
[Haber, Daniel A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Haber, Daniel A.; Sawyers, Charles L.] Howard Hughes Med Inst, Chevy Chase, MD USA.
[Selig, Wendy K. D.] Melanoma Res Alliance, Washington, DC USA.
[Roberts, Samantha A.; Allen, Jeff D.; Sigal, Ellen V.] Friends Canc Res, Washington, DC 20036 USA.
[Ivy, S. Percy] NCI, Invest Drug Branch, CTEP, Rockville, MD USA.
[Sawyers, Charles L.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
RP Roberts, SA (reprint author), Friends Canc Res, 1800 M St NW,Suite 1050 South, Washington, DC 20036 USA.
EM sroberts@focr.org
RI Sawyers, Charles/G-5327-2016
FU Intramural NIH HHS [Z99 CA999999]; NCI NIH HHS [R01 CA129933]
NR 9
TC 10
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U1 0
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD AUG 15
PY 2013
VL 19
IS 16
BP 4297
EP 4304
DI 10.1158/1078-0432.CCR-13-0523
PG 8
WC Oncology
SC Oncology
GA 201NG
UT WOS:000323147700002
PM 23719260
ER
PT J
AU O'Konek, JJ
Kato, S
Takao, S
Izhak, L
Xia, Z
Illarionov, P
Besra, GS
Terabe, M
Berzofsky, JA
AF O'Konek, Jessica J.
Kato, Shingo
Takao, Satomi
Izhak, Liat
Xia, Zheng
Illarionov, Petr
Besra, Gurdyal S.
Terabe, Masaki
Berzofsky, Jay A.
TI beta-Mannosylceramide Activates Type I Natural Killer T Cells to Induce
Tumor Immunity without Inducing Long-Term Functional Anergy
SO CLINICAL CANCER RESEARCH
LA English
DT Article
AB Purpose: Most studies characterizing antitumor properties of invariant natural killer T (iNKT) cells have used the agonist, alpha-galactosylceramide (alpha-GalCer). However, alpha-GalCer induces strong, long-lasting anergy of iNKT cells, which could be a major detriment for clinical therapy. A novel iNKT cell agonist, beta-mannosylceramide (beta-ManCer), induces strong antitumor immunity through a mechanism distinct from that of alpha-GalCer. The objective of this study was to determine whether beta-ManCer induces anergy of iNKT cells.
Experimental Design: Induction of anergy was determined by ex vivo analysis of splenocytes from mice pretreated with iNKT cell agonists as well as in the CT26 lung metastasis in vivo tumor model.
Results: beta-ManCer activated iNKT cells without inducing long-term anergy. The transience of anergy induction correlated with a shortened duration of PD-1 upregulation on iNKT cells activated with beta-ManCer, compared with alpha-GalCer. Moreover, whereas mice pretreated with alpha-GalCer were unable to respond to a second glycolipid stimulation to induce tumor protection for up to 2 months, mice pretreated with beta-ManCer were protected from tumors by a second stimulation equivalently to vehicle-treated mice.
Conclusions: The lack of long-term functional anergy induced by beta-ManCer, which allows for a second dose to still give therapeutic benefit, suggests the strong potential for this iNKT cell agonist to succeed in settings where alpha-GalCer has failed. (C)2013 AACR.
C1 [O'Konek, Jessica J.; Kato, Shingo; Takao, Satomi; Izhak, Liat; Xia, Zheng; Terabe, Masaki; Berzofsky, Jay A.] NCI, Vaccine Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Illarionov, Petr; Besra, Gurdyal S.] Univ Birmingham, Sch Biosci, Birmingham, W Midlands, England.
RP Terabe, M (reprint author), NCI, Vaccine Branch, NIH, Bldg 41,Room D702H,41 Medlars Dr, Bethesda, MD 20892 USA.
EM terabe@mail.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research; Gui
Foundation; Medical Research Council (U.K.); Wellcome Trust
[084923/B/08/7]; Royal Society Wolfson Research Merit Award
FX This work was financially supported by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research and
the Gui Foundation. G.S. Besra received support from the Medical
Research Council (U.K.), the Wellcome Trust (084923/B/08/7), a Royal
Society Wolfson Research Merit Award, and James Bardrick.
NR 28
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U1 0
U2 7
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD AUG 15
PY 2013
VL 19
IS 16
BP 4404
EP 4411
DI 10.1158/1078-0432.CCR-12-2169
PG 8
WC Oncology
SC Oncology
GA 201NG
UT WOS:000323147700013
PM 23804426
ER
PT J
AU Amiri-Kordestani, L
Luchenko, V
Peer, CJ
Ghafourian, K
Reynolds, J
Draper, D
Frye, R
Woo, S
Venzon, D
Wright, J
Skarulis, M
Figg, WD
Fojo, T
Bates, SE
Piekarz, RL
AF Amiri-Kordestani, Laleh
Luchenko, Victoria
Peer, Cody J.
Ghafourian, Kambiz
Reynolds, James
Draper, Deb
Frye, Robin
Woo, Sue
Venzon, David
Wright, John
Skarulis, Monica
Figg, William D.
Fojo, Tito
Bates, Susan E.
Piekarz, Richard L.
TI Phase I Trial of a New Schedule of Romidepsin in Patients with Advanced
Cancers
SO CLINICAL CANCER RESEARCH
LA English
DT Article
AB Purpose: Romidepsin is a potent histone deacetylase inhibitor (HDI) with activity in T-cell lymphoma. Given preclinical data showing greater induction of gene expression with longer exposures to HDIs, a phase I study of a day 1, 3, and 5 romidepsin schedule was evaluated. A secondary objective was to assess the effect of romidepsin on radioactive iodine (RAI) uptake in thyroid cancers.
Experimental Design: Open-label, single-arm, phase I, 3 + 3 dose escalation study. Romidepsin was administered as a 4-hour infusion on days 1, 3, and 5 of a 21-day cycle. Pharmacokinetics (PK) and pharmacodynamics (PD) were assessed, including histone acetylation in peripheral blood mononuclear cells (PBMC), RAI uptake in refractory thyroid cancer, and HDI-related ECG changes.
Results: Twenty-eight patients with solid tumors, including 11 patients with thyroid cancer were enrolled. Six dose levels were explored, and 7 mg/m(2) on days 1, 3, and 5 was identified as tolerable. No Response Evaluation Criteria In Solid Tumors-defined objective responses were recorded although 9 patients had stable disease a median 30 weeks (range, 21-112) including 6 with thyroid cancer a median of 33 weeks. PD studies detected acetylated histones in PBMCs and ECG changes beginning at low dose levels. Follow-up RAI scans in patients with RAI refractory thyroid cancer did not detect meaningful increases.
Conclusions: A romidepsin dose of 7 mg/m(2) administered on days 1, 3, and 5 was found tolerable and resulted in histone acetylation in PBMCs. Although there were no objective responses with romidepsin alone, this schedule may be useful for developing combination studies in solid tumors. (C)2013 AACR.
C1 [Amiri-Kordestani, Laleh; Luchenko, Victoria; Peer, Cody J.; Draper, Deb; Frye, Robin; Woo, Sue; Figg, William D.; Fojo, Tito; Bates, Susan E.; Piekarz, Richard L.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Ghafourian, Kambiz] Washington Hosp Ctr, Dept Cardiol, Bethesda, MD USA.
[Reynolds, James] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Venzon, David] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA.
[Wright, John; Piekarz, Richard L.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Skarulis, Monica] NIDDK, Clin Endocrine Sect, NIH, Bethesda, MD 20892 USA.
RP Bates, SE (reprint author), NCI, Med Oncol Branch, Bldg 10-12N226, Bethesda, MD 20892 USA.
EM batess@helix.nih.gov
RI Figg Sr, William/M-2411-2016
FU NIH, National Cancer Institute, Center for Cancer Research; CRADA
FX This work has been supported, in part, by the Intramural Research
Program of the NIH, National Cancer Institute, Center for Cancer
Research and by a CRADA between the NCI and Celgene Corporation.
NR 42
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U1 0
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD AUG 15
PY 2013
VL 19
IS 16
BP 4499
EP 4507
DI 10.1158/1078-0432.CCR-13-0095
PG 9
WC Oncology
SC Oncology
GA 201NG
UT WOS:000323147700022
PM 23757352
ER
PT J
AU Lin, SW
Wheeler, DC
Park, Y
Spriggs, M
Hollenbeck, AR
Freedman, DM
Abnet, CC
AF Lin, Shih-Wen
Wheeler, David C.
Park, Yikyung
Spriggs, Michael
Hollenbeck, Albert R.
Freedman, D. Michal
Abnet, Christian C.
TI Prospective Study of Ultraviolet Radiation Exposure and Mortality Risk
in the United States
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE epidemiology; mortality; prospective; sunlight; ultraviolet radiation;
vitamin D
ID NONMELANOMA SKIN-CANCER; VITAMIN-D; SOLAR-RADIATION; UV-RADIATION; SUN
EXPOSURE; IMMUNE-SYSTEM; SUNLIGHT; DISEASE; ASSOCIATION; DEATH
AB Geographic variations in mortality rate in the United States could be due to several hypothesized factors, one of which is exposure to solar ultraviolet radiation (UVR). Limited evidence from previous prospective studies has been inconclusive. The association between ambient residential UVR exposure and total and cause-specific mortality risks in a regionally diverse cohort (346,615 white, non-Hispanic subjects, 50-71 years of age, in the National Institutes of Health (NIH)-AARP Diet and Health Study) was assessed, with accounting for individual-level confounders. UVR exposure (averaged for 1978-1993 and 1996-2005) from NASA's Total Ozone Mapping Spectrometer was linked to the US Census Bureau 2000 census tract of participants' baseline residence. Multivariate-adjusted Cox proportional-hazards models were used to estimate hazard ratios and 95% confidence intervals. Over 12 years, UVR exposure was associated with total deaths (n = 41,425; hazard ratio for highest vs. lowest quartiles (HRQ4 (vs.) Q1) = 1.06, 95% confidence interval (CI): 1.03, 1.09; P-trend < 0.001) and with deaths (all P-trend < 0.05) due to cancer (HRQ4 (vs.) Q1 = 1.06, 95% CI: 1.02, 1.11), cardiovascular disease (HRQ4 vs. Q1 = 1.06, 95% CI: 1.00, 1.12), respiratory disease (HRQ4 (vs.) Q1 = 1.37, 95% CI: 1.21, 1.55), and stroke (HRQ4 vs. Q1 = 1.16, 95% CI: 1.01, 1.33) but not with deaths due to injury, diabetes, or infectious disease. These results suggest that UVR exposure might not be beneficial for longevity.
C1 [Lin, Shih-Wen; Park, Yikyung; Freedman, D. Michal; Abnet, Christian C.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Wheeler, David C.] Virginia Commonwealth Univ, Dept Biostat, Sch Med, Richmond, VA USA.
[Spriggs, Michael] Informat Management Serv Inc, Silver Spring, MD USA.
[Hollenbeck, Albert R.] AARP, Washington, DC USA.
RP Lin, SW (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,6E404,MSC9768, Bethesda, MD 20892 USA.
EM lins4@mail.nih.gov
RI Abnet, Christian/C-4111-2015;
OI Abnet, Christian/0000-0002-3008-7843; Park, Yikyung/0000-0002-6281-489X
FU Division of Cancer Epidemiology and Genetics, National Cancer Institute,
National Institutes of Health
FX This research was supported (in part) by the Intramural Research Program
of the Division of Cancer Epidemiology and Genetics, National Cancer
Institute, National Institutes of Health.
NR 49
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PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD AUG 15
PY 2013
VL 178
IS 4
BP 521
EP 533
DI 10.1093/aje/kws589
PG 13
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 200CR
UT WOS:000323045400003
PM 23863757
ER
PT J
AU Zheng, Y
Yu, B
Alexander, D
Manolio, TA
Aguilar, D
Coresh, J
Heiss, G
Boerwinkle, E
Nettleton, JA
AF Zheng, Yan
Yu, Bing
Alexander, Danny
Manolio, Teri A.
Aguilar, David
Coresh, Josef
Heiss, Gerardo
Boerwinkle, Eric
Nettleton, Jennifer A.
TI Associations Between Metabolomic Compounds and Incident Heart Failure
Among African Americans: The ARIC Study
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE heart failure; metabolomics; risk factors
ID ATHEROSCLEROSIS RISK; CARDIOVASCULAR HEALTH; PHYSICAL-ACTIVITY;
BLOOD-PRESSURE; MEN BORN; P-CRESOL; COMMUNITIES; DISEASE; EPIDEMIOLOGY;
FRAMINGHAM
AB Heart failure is more prevalent among African Americans than in the general population. Metabolomic studies among African Americans may efficiently identify novel biomarkers of heart failure. We used untargeted methods to measure 204 stable serum metabolites and evaluated their associations with incident heart failure hospitalization (n = 276) after a median follow-up of 20 years (1987-2008) by using Cox regression in data from 1,744 African Americans aged 45-64 years without heart failure at baseline from the Jackson, Mississippi, field center of the Atherosclerosis Risk in Communities (ARIC) Study. After adjustment for established risk factors, we found that 16 metabolites (6 named with known structural identities and 10 unnamed with unknown structural identities, the latter denoted by using the format X-12345) were associated with incident heart failure (P < 0.0004 based on a modified Bonferroni procedure). Of the 6 named metabolites, 4 are involved in amino acid metabolism, 1 (prolylhydroxyproline) is a dipeptide, and 1 (erythritol) is a sugar alcohol. After additional adjustment for kidney function, 2 metabolites remained associated with incident heart failure (for metabolite X-11308, hazard ratio = 0.75, 95% confidence interval: 0.65, 0.86; for metabolite X-11787, hazard ratio = 1.23, 95% confidence interval: 1.10, 1.37). Further structural analysis revealed X-11308 to be a dihydroxy docosatrienoic acid and X-11787 to be an isoform of either hydroxyleucine or hydroxyisoleucine. Our metabolomic analysis revealed novel biomarkers associated with incident heart failure independent of traditional risk factors.
C1 [Zheng, Yan; Yu, Bing; Boerwinkle, Eric; Nettleton, Jennifer A.] Univ Texas Hlth Sci Ctr Houston, Dept Epidemiol Human Genet & Environm Sci, Houston, TX 77030 USA.
[Manolio, Teri A.] NHGRI, Off Populat Genom, Bethesda, MD 20892 USA.
[Alexander, Danny] Metabolon Inc, Durham, NC USA.
[Aguilar, David] Baylor Coll Med, Div Cardiovasc, Houston, TX 77030 USA.
[Coresh, Josef] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Heiss, Gerardo] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA.
RP Nettleton, JA (reprint author), Suite E641,1200 Hermann Pressler St, Houston, TX 77030 USA.
EM jennifer.a.nettleton@uth.tmc.edu
FU National Heart, Lung, and Blood Institute, National Institutes of Health
[HHSN268201100005C, HHSN 268201100006C, HHSN268201100007C,
HHSN2682011-00008C, HHSN268201100009C, HHSN268201100010C,
HHSN268201100011C, HHSN268201100012C]; National Human Genome Research
Institute [3U01HG004402-02S1]; National Institute of Diabetes and
Digestive and Kidney Diseases, National Institutes of Health
[5K01DK082729-04]; Burroughs Wellcome Fund [1008200]
FX The ARIC Study is a collaborative study supported by the National Heart,
Lung, and Blood Institute, National Institutes of Health, contracts
HHSN268201100005C, HHSN 268201100006C, HHSN268201100007C,
HHSN2682011-00008C, HHSN268201100009C, HHSN268201100010C,
HHSN268201100011C, and HHSN268201100012C. The metabolomics research was
sponsored by the National Human Genome Research Institute
(3U01HG004402-02S1). J. A. N is supported by the National Institute of
Diabetes and Digestive and Kidney Diseases, National Institutes of
Health (5K01DK082729-04). Y. Z. and B. Y. are supported in part by a
training fellowship from the Burroughs Wellcome Fund (grant 1008200).
NR 55
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U1 1
U2 11
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD AUG 15
PY 2013
VL 178
IS 4
BP 534
EP 542
DI 10.1093/aje/kwt004
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 200CR
UT WOS:000323045400004
PM 23788672
ER
PT J
AU Madigan, D
Ryan, PB
Schuemie, M
Stang, PE
Overhage, JM
Hartzema, AG
Suchard, MA
DuMouchel, W
Berlin, JA
AF Madigan, David
Ryan, Patrick B.
Schuemie, Martijn
Stang, Paul E.
Overhage, J. Marc
Hartzema, Abraham G.
Suchard, Marc A.
DuMouchel, William
Berlin, Jesse A.
TI Evaluating the Impact of Database Heterogeneity on Observational Study
Results
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE database; heterogeneity; methods; population characteristics;
reproducibility of results; surveillance
ID MEDICAL OUTCOMES PARTNERSHIP; MYOCARDIAL-INFARCTION; ORAL
BISPHOSPHONATES; RISK; METAANALYSIS; CANCER
AB Clinical studies that use observational databases to evaluate the effects of medical products have become commonplace. Such studies begin by selecting a particular database, a decision that published papers invariably report but do not discuss. Studies of the same issue in different databases, however, can and do generate different results, sometimes with strikingly different clinical implications. In this paper, we systematically study heterogeneity among databases, holding other study methods constant, by exploring relative risk estimates for 53 drug-outcome pairs and 2 widely used study designs (cohort studies and self-controlled case series) across 10 observational databases. When holding the study design constant, our analysis shows that estimated relative risks range from a statistically significant decreased risk to a statistically significant increased risk in 11 of 53 (21%) of drug-outcome pairs that use a cohort design and 19 of 53 (36%) of drug-outcome pairs that use a self-controlled case series design. This exceeds the proportion of pairs that were consistent across databases in both direction and statistical significance, which was 9 of 53 (17%) for cohort studies and 5 of 53 (9%) for self-controlled case series. Our findings show that clinical studies that use observational databases can be sensitive to the choice of database. More attention is needed to consider how the choice of data source may be affecting results.
C1 [Madigan, David] Columbia Univ, Dept Stat, New York, NY 10027 USA.
[Ryan, Patrick B.; Stang, Paul E.; Berlin, Jesse A.] Janssen Res & Dev LLC, Titusville, NJ USA.
[Schuemie, Martijn] Erasmus Univ, Dept Med Informat, Med Ctr Rotterdam, NL-3000 DR Rotterdam, Netherlands.
[Overhage, J. Marc] Ctr Biomed Informat, Regenstrief Inst, Indianapolis, IN USA.
[Overhage, J. Marc] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
[Hartzema, Abraham G.] Univ Florida, Coll Pharm, Gainesville, FL 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.
[Suchard, Marc A.] Univ Calif Los Angeles, Dept Biostat, Fielding Sch Publ Hlth, Los Angeles, CA USA.
[DuMouchel, William] Oracle Hlth Sci, Burlington, MA USA.
[Madigan, David; Ryan, Patrick B.; Schuemie, Martijn; Stang, Paul E.; Overhage, J. Marc; Hartzema, Abraham G.; Suchard, Marc A.; DuMouchel, William; Berlin, Jesse A.] Fdn Natl Inst Hlth, Observat Med Outcomes Partnership, Bethesda, MD USA.
[Hartzema, Abraham G.] US FDA, Rockville, MD 20857 USA.
RP Madigan, D (reprint author), Columbia Univ, Dept Stat, 1255 Amsterdam Ave, New York, NY 10027 USA.
EM david.madigan@columbia.edu
OI Overhage, Joseph/0000-0003-0223-0195
FU Foundation for the National Institutes of Health through Abbott
Laboratories, Ltd.; Foundation for the National Institutes of Health
through Amgen, Inc.; Foundation for the National Institutes of Health
through AstraZeneca, PLC; Foundation for the National Institutes of
Health through Bayer Healthcare Pharmaceuticals, Inc.; Foundation for
the National Institutes of Health through Bristol-Myers Squibb Company;
Foundation for the National Institutes of Health through Eli Lilly Co.;
Foundation for the National Institutes of Health through
GlaxoSmithKline, PLC; Foundation for the National Institutes of Health
through Janssen Research and Development, LLC; Foundation for the
National Institutes of Health through Lundbeck, Inc.; Foundation for the
National Institutes of Health through Merck Co., Inc.; Foundation for
the National Institutes of Health through Novartis Pharmaceuticals
Corp.; Foundation for the National Institutes of Health through Pfizer,
Inc.; Foundation for the National Institutes of Health through
Pharmaceutical Research Manufacturers of America; Foundation for the
National Institutes of Health through F. Hoffmann-La Roche, Ltd.;
Foundation for the National Institutes of Health through Sanofi, SA;
Foundation for the National Institutes of Health through Schering-Plough
Corp.; Foundation for the National Institutes of Health through Takeda
Pharmaceutical Co., Ltd.
FX The Observational Medical Outcomes Partnership is funded by the
Foundation for the National Institutes of Health through generous
contributions from the following: Abbott Laboratories, Ltd.; Amgen,
Inc.; AstraZeneca, PLC; Bayer Healthcare Pharmaceuticals, Inc.;
Bristol-Myers Squibb Company; Eli Lilly & Co.; GlaxoSmithKline, PLC;
Janssen Research and Development, LLC, Lundbeck, Inc.; Merck & Co.,
Inc.; Novartis Pharmaceuticals Corp.; Pfizer, Inc.; Pharmaceutical
Research Manufacturers of America; F. Hoffmann-La Roche, Ltd.; Sanofi,
SA; Schering-Plough Corp.; and Takeda Pharmaceutical Co., Ltd.
NR 25
TC 44
Z9 44
U1 0
U2 8
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD AUG 15
PY 2013
VL 178
IS 4
BP 645
EP 651
DI 10.1093/aje/kwt010
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 200CR
UT WOS:000323045400015
PM 23648805
ER
PT J
AU Salas, LA
Cantor, KP
Tardon, A
Serra, C
Carrato, A
Garcia-Closas, R
Rothman, N
Malats, N
Silverman, D
Kogevinas, M
Villanueva, CM
AF Salas, Lucas A.
Cantor, Kenneth P.
Tardon, Adonina
Serra, Consol
Carrato, Alfredo
Garcia-Closas, Reina
Rothman, Nathaniel
Malats, Nuria
Silverman, Debra
Kogevinas, Manolis
Villanueva, Cristina M.
TI Biological and Statistical Approaches for Modeling Exposure to Specific
Trihalomethanes and Bladder Cancer Risk
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE chloroform; complex mixtures; logistic models; principal-components
analysis; Spain; trihalomethanes; urinary bladder neoplasms
ID DISINFECTION BY-PRODUCTS; EVALUATING SUFFICIENT SIMILARITY; PRINCIPAL
COMPONENT ESTIMATION; DRINKING-WATER SOURCE; CHEMICAL-MIXTURES;
HALOACETIC ACIDS; RECTAL CANCERS; TREATED WATER; DBP MIXTURES;
REGRESSION
AB Lifetime exposure to trihalomethanes (THM) has been associated with increased risk of bladder cancer. We explored methods of analyzing bladder cancer risk associated with 4 THM (chloroform, bromodichloromethane, dibromochloromethane, and bromoform) as surrogates for disinfection by-product (DBP) mixtures in a case-control study in Spain (1998-2001). Lifetime average concentrations of THM in the households of 686 incident bladder cancer cases and 750 matched hospital-based controls were calculated. Several exposure metrics were modeled through conditional logistic regression, including the following analyses: total THM (mu g/L), cytotoxicity-weighted sum of total THM (pmol/L), 4 THM in separate models, 4 THM in 1 model, chloroform and the sum of brominated THM in 1 model, and a principal-components analysis. THM composition, concentrations, and correlations varied between areas. The model for total THM was stable and showed increasing dose-response trends. Models for separate THM provided unstable estimates and inconsistent dose-response relationships. Risk estimation for specific THM is hampered by the varying composition of the mixture, correlation between species, and imprecision of historical estimates. Total THM (mu g/L) provided a proxy measure of DBPs that yielded the strongest dose-response relationship with bladder cancer risk. A variety of metrics and statistical approaches should be used to evaluate this association in other settings.
C1 [Salas, Lucas A.; Kogevinas, Manolis; Villanueva, Cristina M.] Ctr Res Environm Epidemiol, Barcelona 08003, Spain.
[Salas, Lucas A.; Kogevinas, Manolis; Villanueva, Cristina M.] Hosp del Mar, Med Res Inst, Barcelona, Spain.
[Salas, Lucas A.] Pompeu Fabra Univ, Dept Expt & Hlth Sci, Barcelona, Spain.
[Cantor, Kenneth P.; Rothman, Nathaniel; Silverman, Debra] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Tardon, Adonina] Univ Oviedo, Dept Prevent Med & Publ Hlth, Fac Med, Oviedo, Spain.
[Tardon, Adonina; Kogevinas, Manolis; Villanueva, Cristina M.] CIBER Epidemiol & Salud Publ, Barcelona, Spain.
[Serra, Consol] Univ Pompeu Fabra, Ctr Res Occupat Hlth, Barcelona, Spain.
[Serra, Consol] Consorci Hosp Parc Tauli, Sabadell, Spain.
[Carrato, Alfredo] Ramon y Cajal Univ Hosp, Dept Med Oncol, Madrid, Spain.
[Garcia-Closas, Reina] Canarias Univ Hosp, Res Unit, San Cristobal la Laguna, Spain.
[Malats, Nuria] Spanish Natl Canc Res Ctr, Madrid, Spain.
[Kogevinas, Manolis] Natl Sch Publ Hlth, Athens, Greece.
RP Villanueva, CM (reprint author), Ctr Res Environm Epidemiol, Barcelona Biomed Res Pk,Dr Aiguader 88, Barcelona 08003, Spain.
EM cvillanueva@creal.cat
RI Serra, C/E-6879-2014; Malats, Nuria/H-7041-2015; Villanueva,
Cristina/N-1942-2014; Kogevinas, Manolis/C-3918-2017;
OI Serra, C/0000-0001-8337-8356; Malats, Nuria/0000-0003-2538-3784;
Villanueva, Cristina/0000-0002-0783-1259; Salas, Lucas
A/0000-0002-2279-4097
FU US National Institutes of Health, National Cancer Institute, Division of
Cancer Epidemiology and Genetics [NCI NO2-CP-11015]; Spanish Health
Ministry [FIS/Spain 00/0745, ISIII-GO3/174]; European Union
[BMH4-98-3243]; Erasmus Columbus Master Scholarship
[2009-5123/001-001-ECW]; Colciencias PhD Scholarship [529/2011]
FX This study was supported in part by the Intramural Research Program of
the US National Institutes of Health, National Cancer Institute,
Division of Cancer Epidemiology and Genetics (contract NCI
NO2-CP-11015). The project also received funding from the Spanish Health
Ministry (grants FIS/Spain 00/0745 and ISIII-GO3/174) and the European
Union (grant BMH4-98-3243). The current analyses were supported by an
Erasmus Columbus Master Scholarship (grant 2009-5123/001-001-ECW to L.
A. Salas) and a Colciencias PhD Scholarship (grant 529/2011 to L. A.
Salas).
NR 50
TC 2
Z9 3
U1 1
U2 25
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD AUG 15
PY 2013
VL 178
IS 4
BP 652
EP 660
DI 10.1093/aje/kwt009
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 200CR
UT WOS:000323045400016
PM 23648803
ER
PT J
AU Sun, HM
Xia, MH
Shahane, SA
Jadhav, A
Austin, CP
Huang, RL
AF Sun, Hongmao
Xia, Menghang
Shahane, Sampada A.
Jadhav, Ajit
Austin, Christopher P.
Huang, Ruili
TI Are hERG channel blockers also phospholipidosis inducers?
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE hERG; Phospholipidosis; qHTS
ID LONG QT SYNDROME; NMR-SPECTROSCOPY; MEMBRANE
AB Both pharmacophore models of the human ether-A-go-go-related gene (hERG) channel blockers and phospholipidosis (PLO) inducers contain a hydrophobic moiety and a hydrophilic motif/positively charged center, so it is interesting to investigate the overlap between the ligand chemical spaces of both targets. We have assayed over 4000 non-redundant drug-like compounds for both their hERG inhibitory activity and PLD inducing potential in a quantitative high throughput screening (qHTS) format. Seventy-seven percent of PLD inducing compounds identified from the screening were also found to be hERG channel blockers, and 96.9% of the dually active compounds were positively charged. Among the 48 compounds that induced PLD without inhibiting hERG channel, 24 compounds (50.0%) carried steroidal structures. According to our results, hERG channel blockers and PLD inducers share a large chemical space. In addition, a positively charged hERG channel blocker will most likely induce PLD, while a steroid PLD inducer is less likely a hERG channel blocker.
C1 [Sun, Hongmao; Xia, Menghang; Shahane, Sampada A.; Jadhav, Ajit; Austin, Christopher P.; Huang, Ruili] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
RP Sun, HM (reprint author), NIH, Natl Ctr Adv Translat Sci, 9800 Med Ctr Dr, Bethesda, MD 20892 USA.
EM sunh7@mail.nih.gov
FU NIEHS NIH HHS [Y02 ES007020]
NR 18
TC 10
Z9 10
U1 0
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD AUG 15
PY 2013
VL 23
IS 16
BP 4587
EP 4590
DI 10.1016/j.bmcl.2013.06.034
PG 4
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 194DT
UT WOS:000322611900019
PM 23856051
ER
PT J
AU Murugan, RN
Jacob, B
Kim, EH
Ahn, M
Sohn, H
Seo, JH
Cheong, C
Hyun, JK
Lee, KS
Shin, SY
Bang, JK
AF Murugan, Ravichandran N.
Jacob, Binu
Kim, Eun-Hee
Ahn, Mija
Sohn, Hoik
Seo, Ji-Hyung
Cheong, Chaejoon
Hyun, Jae-Kyung
Lee, Kyung S.
Shin, Song Yub
Bang, Jeong Kyu
TI Non hemolytic short peptidomimetics as a new class of potent and
broad-spectrum antimicrobial agents
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Short antimicrobial peptidomimetics; Methicillin-resistance
Staphylococcus aureus; Proteolytic stability
ID PEPTIDES
AB Since the bacterial resistance to antibiotics is increasing rapidly, numerous studies have contributed to the design and synthesis of potent synthetic mimics of antimicrobial peptides (AMPs). In an attempt to find the pharmacophore of short antimicrobial peptidomimetics through systematic tuning of hydrophobic and hydrophilic patterns, we have identified a set of short histidine-derived antimicrobial peptides (SAMPs) with potent and broad-spectrum activity. A combination of high antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA), without hemolytic activity and proteolytic stability makes these molecules promising candidates for novel antimicrobial therapeutics. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Murugan, Ravichandran N.; Kim, Eun-Hee; Ahn, Mija; Seo, Ji-Hyung; Cheong, Chaejoon; Bang, Jeong Kyu] Korea Basic Sci Inst, Div Magnet Resonance, Ochang 363883, Chung Buk, South Korea.
[Jacob, Binu; Shin, Song Yub] Chosun Univ, Grad Sch, Dept Biomat, Kwangju 501759, South Korea.
[Jacob, Binu; Shin, Song Yub] Chosun Univ, Sch Med, Dept Cellular & Mol Med, Kwangju 501759, South Korea.
[Sohn, Hoik] Univ Texas Austin, Dept Chem & Biochem, Coll Nat Sci, Austin, TX 78712 USA.
[Hyun, Jae-Kyung] Korea Basic Sci Inst, Div Electron Micorscop Res, Taejon 305333, South Korea.
[Lee, Kyung S.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Shin, SY (reprint author), Chosun Univ, Grad Sch, Dept Biomat, Kwangju 501759, South Korea.
EM syshin@chosun.ac.kr; bangjk@kbsi.re.kr
RI Jacob, Binu/K-7621-2016
OI Jacob, Binu/0000-0002-2770-8741
FU Korea Basic Science Institute [T33418, T33518]; National Cancer
Institute; Korea Research Foundation; Korean Government
[KRF-2011-0009039]
FX This work was supported in part by the Korea Basic Science Institute's
research grant T33418 (J.K.B.), T33518 (J-K.H.), the National Cancer
Institute's Intramural Research grant (K.S.L.) and the Korea Research
Foundation funded by the Korean Government (KRF-2011-0009039 to S.Y.S.).
NR 8
TC 11
Z9 12
U1 0
U2 22
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
EI 1464-3405
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD AUG 15
PY 2013
VL 23
IS 16
BP 4633
EP 4636
DI 10.1016/j.bmcl.2013.06.016
PG 4
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 194DT
UT WOS:000322611900027
PM 23816372
ER
PT J
AU dos Santos, ED
Hamel, E
Bai, RL
Burnett, JC
Tozatti, CSS
Bogo, D
Perdomo, RT
Antunes, AMM
Marques, MM
Matos, MDC
de Lima, DP
AF dos Santos, Edson dos A.
Hamel, Ernest
Bai, Ruoli
Burnett, James C.
Suniga Tozatti, Camila Santos
Bogo, Danielle
Perdomo, Renata T.
Antunes, Alexandra M. M.
Matilde Marques, M.
Matos, Maria de F. C.
de Lima, Denis P.
TI Synthesis and evaluation of diaryl sulfides and diaryl selenide
compounds for antitubulin and cytotoxic activity
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Diaryl selenide; Diaryl sulfide; Combretastatin A-4; Tubulin;
Cytotoxicity
ID TUBULIN POLYMERIZATION; COMBRETASTATIN A-4; BIOLOGICAL EVALUATION;
ANTINEOPLASTIC AGENTS; INHIBITORS; DERIVATIVES; COLCHICINE; ANALOGS;
SULFUR
AB We have devised a procedure for the synthesis of analogs of combretastatin A-4 (CA-4) containing sulfur and selenium atoms as spacer groups between the aromatic rings. CA-4 is well known for its potent activity as an inhibitor of tubulin polymerization, and its prodrugs combretastatin A-4 phosphate (CA-4P) and combretastatin A-1 phosphate (CA-1P) are being investigated as antitumor agents that cause tumor vascular collapse in addition to their activity as cytotoxic compounds. Here we report the preparation of two sulfur analogs and one selenium analog of CA-4. All synthesized compounds, as well as several synthetic intermediates, were evaluated for inhibition of tubulin polymerization and for cytotoxic activity in human cancer cells. Compounds 3 and 4 were active at nM concentration against MCF-7 breast cancer cells. As inhibitors of tubulin polymerization, both 3 and 4 were more active than CA-4 itself. In addition, 4 was the most active of these agents against 786, HT-29 and PC-3 cancer cells. Molecular modeling binding studies are also reported for compounds 1, 3, 4 and CA-4 to tubulin within the colchicine site. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [dos Santos, Edson dos A.; Suniga Tozatti, Camila Santos; de Lima, Denis P.] Univ Fed Mato Grosso do Sul, Inst Quim, Lab LP4, BR-79070900 Campo Grande, MS, Brazil.
[Hamel, Ernest; Bai, Ruoli] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,FNLCR, Ft Detrick, MD 21702 USA.
[Burnett, James C.] NCI, Computat Drug Dev Grp, Dev Therapeut Program, FNLCR, Frederick, MD 21702 USA.
[Bogo, Danielle; Perdomo, Renata T.; Matos, Maria de F. C.] Univ Fed Mato Grosso do Sul, Lab Biol Mol & Culturas Celulares CBS, BR-79070900 Campo Grande, MS, Brazil.
[Antunes, Alexandra M. M.; Matilde Marques, M.] Univ Tecn Lisboa, Inst Super Tecn, Ctr Quim Estrutural, P-1049001 Lisbon, Portugal.
RP de Lima, DP (reprint author), Univ Fed Mato Grosso do Sul, Inst Quim, Lab LP4, Av Filinto Muller, BR-79070900 Campo Grande, MS, Brazil.
EM denis.lima@ufms.br
RI Marques, M. Matilde/E-2535-2012; PTMS, RNEM/C-1589-2014; de Lima,
Denis/D-7039-2014; Antunes, Alexandra/B-7871-2009; dos Santos,
Edson/I-6324-2016
OI Marques, M. Matilde/0000-0002-7526-4962; de Lima,
Denis/0000-0002-6023-4867; Antunes, Alexandra/0000-0003-1827-7369;
FU CQE-IST; ERASMUS-MUNDUS; FUNDECT-MS; CNPq; PROPP-UFMS; UFMS; National
Cancer Institute, National Institutes of Health [HHSN261200800001E];
Fundacao para a Ciencia e a Tecnologia (FCT, Portugal)
[PEst-OE/QUI/UI0100/2011, PEst-OE/QUI/UI0100/2013]
FX The authors thank Dr. Roberto da Silva Gomes for providing mass spectra
of some compounds. We are indebted to CQE-IST, ERASMUS-MUNDUS,
FUNDECT-MS, CNPq and PROPP-UFMS for financial support and scholarships.
We also thank UFMS and CQE-IST that supported this work. For J.C.B., in
accordance with SAIC-Frederick, Inc. contractual requirements, the
following statement is required: this project has been funded in whole
or in part with federal funds from the National Cancer Institute,
National Institutes of Health, under contract no. HHSN261200800001E.
This work was also supported by Fundacao para a Ciencia e a Tecnologia
(FCT, Portugal), through pluriannual funds to Centro de Quimica
Estrutural (PEst-OE/QUI/UI0100/2011 and PEst-OE/QUI/UI0100/2013).
NR 28
TC 11
Z9 11
U1 0
U2 20
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
EI 1464-3405
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD AUG 15
PY 2013
VL 23
IS 16
BP 4669
EP 4673
DI 10.1016/j.bmcl.2013.06.009
PG 5
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 194DT
UT WOS:000322611900035
ER
PT J
AU Jedhe, GS
Paul, D
Gonnade, RG
Santra, MK
Hamel, E
Nguyen, TL
Sanjayan, GJ
AF Jedhe, Ganesh S.
Paul, Debasish
Gonnade, Rajesh G.
Santra, Manas K.
Hamel, Ernest
Tam Luong Nguyen
Sanjayan, Gangadhar J.
TI Correlation of hydrogen-bonding propensity and anticancer profile of
tetrazole-tethered combretastatin analogues
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Combretastatin; Tetrazole; Crystal; Colchicine; Tubulin
ID ANTINEOPLASTIC AGENTS; BIOLOGICAL EVALUATION; ANTITUMOR-ACTIVITY; A-4
ANALOGS; TUBULIN; INHIBITORS; PHOSPHATE; POTENT; METABOLISM; COLCHICINE
AB A series of 1,5-disubstituted tetrazole-tethered combretastatin analogues with extended hydrogen-bond donors at the ortho-positions of the aryl A and B rings were developed and evaluated for their antitubulin and antiproliferative activity. We wanted to test whether intramolecular hydrogen-bonding used as a conformational locking element in these analogues would improve their activity. The correlation of crystal structures with the antitubulin and antiproliferative profiles of the modified analogues suggested that hydrogen-bond-mediated conformational control of the A ring is deleterious to the bioactivity. In contrast, although there was no clear evidence that intramolecular hydrogen bonding to the B ring enhanced activity, we found that increased substitution on the B ring had a positive effect on antitubulin and antiproliferative activity. Among the various analogues synthesized, compounds 5d and 5e, having hydrogen-bonding donor groups at the ortho and meta-positions on the 4-methoxy phenyl B ring, are strong inhibitors of tubulin polymerization and antiproliferative agents having IC50 value in micromolar concentrations. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Jedhe, Ganesh S.; Sanjayan, Gangadhar J.] Natl Chem Lab, Div Organ Chem, Pune 411008, Maharashtra, India.
[Paul, Debasish; Santra, Manas K.] Univ Pune Campus, Natl Ctr Cell Sci, Pune 411007, Maharashtra, India.
[Gonnade, Rajesh G.] Natl Chem Lab, Ctr Mat Characterizat, Pune 411008, Maharashtra, India.
[Hamel, Ernest] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,Frederick Natl Lab Canc, Frederick, MD 21702 USA.
[Tam Luong Nguyen] Frederick Natl Lab Canc Res, Target Struct Based Drug Discovery Grp, SAIC Frederick, Frederick, MD 21702 USA.
RP Hamel, E (reprint author), NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,Frederick Natl Lab Canc, Frederick, MD 21702 USA.
EM gj.sanjayan@ncl.res.in
RI Jedhe, Ganesh/M-9019-2015
OI Jedhe, Ganesh/0000-0001-7404-3677
FU CSIR, New Delhi; CSIR-Biodiversity programme [BSC-0120]; National Cancer
Institute, National Institutes of Health [N01-CO-12400]; Developmental
Therapeutics Program in the Division of Cancer Treatment and Diagnosis
of the National Cancer Institute
FX G.S.J. is thankful to CSIR, New Delhi, for a research fellowship. G.J.S.
thanks CSIR-Biodiversity programme (BSC-0120) for funding this project.
This project has been funded in part with federal funds from the
National Cancer Institute, National Institutes of Health, under contract
N01-CO-12400. 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 US Government. This research was
supported in part by the Developmental Therapeutics Program in the
Division of Cancer Treatment and Diagnosis of the National Cancer
Institute.
NR 37
TC 10
Z9 10
U1 0
U2 15
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
EI 1464-3405
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD AUG 15
PY 2013
VL 23
IS 16
BP 4680
EP 4684
DI 10.1016/j.bmcl.2013.06.004
PG 5
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 194DT
UT WOS:000322611900037
PM 23809851
ER
PT J
AU Miranda, TB
Voss, TC
Sung, MH
Baek, S
John, S
Hawkins, M
Grontved, L
Schiltz, RL
Hager, GL
AF Miranda, Tina B.
Voss, Ty C.
Sung, Myong-Hee
Baek, Songjoon
John, Sam
Hawkins, Mary
Grontved, Lars
Schiltz, R. Louis
Hager, Gordon L.
TI Reprogramming the Chromatin Landscape: Interplay of the Estrogen and
Glucocorticoid Receptors at the Genomic Level
SO CANCER RESEARCH
LA English
DT Article
ID BREAST-CANCER-CELLS; RESPONSE ELEMENT; IN-VIVO; EXPRESSION; ACTIVATION;
BINDING; DNA; DEXAMETHASONE; PROGESTERONE; ACCESSIBILITY
AB Cross-talk between estrogen receptors (ER) and glucocorticoid receptors (GR) has been shown to contribute to the development and progression of breast cancer. Importantly, the ER and GR status in breast cancer cells is a significant factor in determining the outcome of the disease. However, mechanistic details defining the cellular interactions between ER and GR are poorly understood. Weinvestigated genome-wide binding profiles for ER and GR upon coactivation and characterized the status of the chromatin landscape. We describe a novel mechanism dictating the molecular interplay between ER and GR. Upon induction, GR modulates access of ER to specific sites in the genome by reorganization of the chromatin configuration for these elements. Binding to these newly accessible sites occurs either by direct recognition of ER response elements or indirectly through interactions with other factors. The unveiling of this mechanism is important for understanding cellular interactions between ER and GR and may represent a general mechanism for cross-talk between nuclear receptors in human disease. (C) 2013 AACR.
C1 [Miranda, Tina B.; Voss, Ty C.; Sung, Myong-Hee; Baek, Songjoon; John, Sam; Hawkins, Mary; Grontved, Lars; Schiltz, R. Louis; Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
RP Hager, GL (reprint author), NCI, 41 Lib Dr, Bethesda, MD 20892 USA.
EM hagerg@exchange.nih.gov
OI Grontved, Lars/0000-0002-6735-8483
FU NIH, National Cancer Institute, Center for Cancer Research; National
Institute of General Medical Sciences Pharmacological Research and
Training Fellowship; Lundbeck Foundation
FX This research was supported, in part, by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research. T. B.
Miranda was supported, in part, by a National Institute of General
Medical Sciences Pharmacological Research and Training Fellowship. L.
Grontved was supported by a research grant from the Lundbeck Foundation.
NR 40
TC 30
Z9 30
U1 2
U2 10
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD AUG 15
PY 2013
VL 73
IS 16
BP 5130
EP 5139
DI 10.1158/0008-5472.CAN-13-0742
PG 10
WC Oncology
SC Oncology
GA 201RX
UT WOS:000323161800017
PM 23803465
ER
PT J
AU Sanghvi, M
Ramamoorthy, A
Strait, J
Wainer, IW
Moaddel, R
AF Sanghvi, M.
Ramamoorthy, A.
Strait, J.
Wainer, I. W.
Moaddel, R.
TI Development and validation of a sensitive LC-MS/MS method for the
determination of fenoterol in human plasma and urine samples
SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL
AND LIFE SCIENCES
LA English
DT Article
DE Congestive heart failure; Bioavailability; Chirobiotic T;
beta(2)-Adrenergic receptor agonist
ID MASS-SPECTROMETRY; SEPARATION; RAT; DERIVATIZATION; ENANTIOMERS;
DERIVATIVES; METABOLISM; HPLC
AB Due to the lack of sensitivity in current methods for the determination of fenoterol (Fen), a rapid LC-MS/MS method was developed for the determination of (R,R')-Fen and (R,R';S,S')-Fen in plasma and urine. The method was fully validated and was linear from 50 pg/ml to 2000 pg/ml for plasma and from 2.500 ng/ml to 160 ng/ml for urine with a lower limit of quantitation of 52.8 pg/ml in plasma. The coefficient of variation was <15% for the high QC standards and <10% for the low QC standards in plasma and was <15% for the high and low QC standards in urine. The relative concentrations of (R,R')-Fen and (S,S')Fen were determined using a chirobiotic T chiral stationary phase. The method was used to determine the concentration of (R,R')-Fen in plasma and urine samples obtained in an oral cross-over study of (R,R')Fen and (R,R';S,S')-Fen formulations. The results demonstrated a potential pre-systemic enantioselective interaction in which the (S,S')-Fen reduces the sulfation of the active (R,R')-Fen. The data suggest that a non-racemic mixture of the Fen enantiomers may provide better bioavailability of the active (R,R')-Fen for use in the treatment of cardiovascular disease. Published by Elsevier B.V.
C1 [Sanghvi, M.; Ramamoorthy, A.; Wainer, I. W.; Moaddel, R.] NIA, Clin Invest Lab, Div Intramural Res Programs, NIH, Baltimore, MD 21224 USA.
[Strait, J.] NIA, Cardiovasc Sci Lab, Div Intramural Res Programs, NIH, Baltimore, MD 21224 USA.
RP Moaddel, R (reprint author), NIA, Clin Invest Lab, Biomed Res Ctr, NIH, 8C232,251 Bayview Blvd, Baltimore, MD 21224 USA.
EM moaddelru@mail.nih.gov
FU National Institute on Aging/NIH
FX This research was supported by the Intramural Research Program of the
National Institute on Aging/NIH.
NR 24
TC 2
Z9 2
U1 1
U2 14
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1570-0232
J9 J CHROMATOGR B
JI J. Chromatogr. B
PD AUG 15
PY 2013
VL 933
BP 37
EP 43
DI 10.1016/j.jchromb.2013.06.020
PG 7
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 198MM
UT WOS:000322927000006
PM 23872161
ER
PT J
AU Zhang, JW
Ferre-D'Amare, AR
AF Zhang, Jinwei
Ferre-D'Amare, Adrian R.
TI Co-crystal structure of a T-box riboswitch stem I domain in complex with
its cognate tRNA
SO NATURE
LA English
DT Article
ID AMINOACYL-TRANSFER-RNA; RIBOSOMAL-RNA; BACILLUS-SUBTILIS;
RIBONUCLEASE-P; ANTITERMINATION; MOTIF; RECOGNITION; SYNTHETASE;
TRNA(GLY); FEATURES
AB In Gram-positive bacteria, T-box riboswitches regulate the expression of aminoacyl-tRNA synthetases and other proteins in response to fluctuating transfer RNA aminoacylation levels under various nutritional states(1). T-boxes reside in the 5'-untranslated regions of the messenger RNAs they regulate, and consist of two conserved domains. Stem I contains the specifier trinucleotide that base pairs with the anticodon of cognate tRNA. 3' to stem I is the antiterminator domain, which base pairs with the tRNA acceptor end and evaluates its aminoacylation state(2). Despite high phylogenetic conservation and widespread occurrence in pathogens, the structural basis of tRNA recognition(3,4) by this riboswitch remains ill defined. Here we demonstrate that the similar to 100-nucleotide T-box stem I is necessary and sufficient for specific, high-affinity (dissociation constant (K-d) similar to 150 nM) tRNA binding, and report the structure of Oceanobacillus iheyensis glyQ stem I in complex with its cognate tRNA at 3.2 angstrom resolution. Stem I recognizes the overall architecture of tRNA in addition to its anticodon, something accomplished by large ribonucleoproteins such as the ribosome, or proteins such as aminoacyl-tRNA synthetases(5), but is unprecedented for a compact mRNA domain. The C-shaped stem I cradles the L-shaped tRNA, forming an extended (1,604 angstrom(2)) intermolecular interface. In addition to the specifier-anticodon interaction, two interdigitated T-loops near the apex of stem I stack on the tRNA elbow in a manner analogous to those of the J11/12-J12/11 motif(6) of RNase P and the L1 stalk(7) of the ribosomal E-site. Because these ribonucleoproteins and T-boxes are unrelated, this strategy to recognize a universal tRNA feature probably evolved convergently. Mutually induced fit of stem I and the tRNA exploiting the intrinsic flexibility of tRNA and its conserved post-transcriptional modifications results in high shape complementarity, which in addition to providing specificity and affinity, globally organizes the T-box to orchestrate tRNA-dependent transcription regulation.
C1 [Zhang, Jinwei; Ferre-D'Amare, Adrian R.] NHLBI, Bethesda, MD 20892 USA.
RP Ferre-D'Amare, AR (reprint author), NHLBI, 50 South Dr,MSC 8012, Bethesda, MD 20892 USA.
EM adrian.ferre@nih.gov
FU National Institute for General Medical Sciences, National Institutes of
Health (NIH); US Department of Energy; intramural program of the
National Heart, Lung, and Blood Institute, NIH
FX We thank the staff at beamlines 24-ID-C and 24-ID-E of APS and 5.0.1 and
5.0.2 of the ALS for crystallographic data collection support, G.
Piszczek for ITC support, R. Levine and D.-Y. Lee for help with mass
spectrometry, K. Perry and K. R. Rajashankar for assistance with initial
crystallographic phasing, and N. Baird, T. Hamma, C. Jones, M. Lau, J.
Posakony, A. Roll-Mecak, O. Uhlenbeck and K. Warner for discussions.
This work is partly based on research conducted at the APS on the
Northeastern Collaborative Access Team (NE-CAT) beamlines, and at the
ALS on the Berkeley Center for Structural Biology beamlines, which are
both supported by the National Institute for General Medical Sciences,
National Institutes of Health (NIH). Use of ALS and APS was supported by
the US Department of Energy. This work was supported in part by the
intramural program of the National Heart, Lung, and Blood Institute,
NIH.
NR 52
TC 42
Z9 45
U1 2
U2 60
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD AUG 15
PY 2013
VL 500
IS 7462
BP 363
EP +
DI 10.1038/nature12440
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 201AF
UT WOS:000323112400039
PM 23892783
ER
PT J
AU Shuch, B
Hanley, J
Lai, J
Vourganti, S
Kim, SP
Setodji, CM
Dick, AW
Chow, WH
Saigal, C
AF Shuch, Brian
Hanley, Janet
Lai, Julie
Vourganti, Srinivas
Kim, Simon P.
Setodji, Claude M.
Dick, Andrew W.
Chow, Wong-Ho
Saigal, Chris
CA Urologic Dis Amer Project
TI Overall survival advantage with partial nephrectomy: A bias of
observational data?
SO CANCER
LA English
DT Article
DE partial nephrectomy; radical nephrectomy; survival advantage;
observational data; selection bias
ID RENAL-CELL CARCINOMA; NEPHRON-SPARING SURGERY; CHRONIC KIDNEY-DISEASE;
NORMAL CONTRALATERAL KIDNEY; RADICAL NEPHRECTOMY; MORTALITY; CANCER;
TUMOR; METAANALYSIS; COMORBIDITY
AB BACKGROUND: Partial nephrectomy (PN) and radical nephrectomy (RN) are standard treatments for a small renal mass. Retrospective studies suggest an overall survival (OS) advantage, however a randomized phase 3 trial suggests otherwise. The effects of both surgical modalities on OS were evaluated compared with controls. METHODS: A matched cohort study was performed using the Surveillance, Epidemiology, and End Results (SEER)-Medicare dataset. Individuals treated with PN or RN for localized renal cell carcinoma (RCC) measuring <= 4 cm were compared with 2 control groups (non-muscle-invasive bladder cancer (BCC) and noncancer controls (NCC). Using a greedy algorithm, RCC groups were matched with controls by demographics and comorbidities. OS for surgical groups and controls were compared. The cause of death was evaluated for cancer groups when differences in OS were noted. RESULTS: Patients undergoing PN and RN were matched with controls. All cancer groups had >95% 10-year cancer-specific survival (CSS). Median OS was similar between RN (9.05 years) and BCC (8.67 years; P = .067) and NCC (8.77 years; P = .49). Median OS was improved for PN (10.45 years) compared with BCC (8.75 years; P <. 001) and NCC controls (8.76 years; P < .001). A multivariate Cox hazards model demonstrated that PN improved OS compared with NCC (hazard ratio, 1.257; P < .001) and BCC (hazard ratio, 1.364; P<. 001). CONCLUSIONS: RN patients had similar OS compared with controls, suggesting that this treatment modality does not compromise survival. Patients undergoing PN had improved OS compared with controls, suggesting possible selection bias. The apparent survival advantage conferred by PN in SEER-Medicare case series is likely the result of selection bias involving unmeasured confounders. Cancer 2013; 119: 2981-9. (C) 2013 American Cancer Society.
C1 [Shuch, Brian; Kim, Simon P.] Yale Univ, Sch Med, Dept Urol, New Haven, CT USA.
[Shuch, Brian; Vourganti, Srinivas] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
[Hanley, Janet; Lai, Julie; Setodji, Claude M.; Dick, Andrew W.] RAND Corp, Santa Monica, CA USA.
[Kim, Simon P.] Mayo Clin, Rochester, MN USA.
[Chow, Wong-Ho] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Saigal, Chris] Univ Calif Los Angeles, Sch Med, Dept Urol, Inst Urol Oncol, Los Angeles, CA USA.
RP Shuch, B (reprint author), NCI, Urol Oncol Branch, Bldg 10 CRC Room 1-5940, Bethesda, MD 20892 USA.
EM brian.shuch@yale.edu
FU National Institutes of Health [HHSN276201200016C]
FX The Urologic Disease of America Project is supported by National
Institutes of Health grant HHSN276201200016C.
NR 31
TC 29
Z9 29
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD AUG 15
PY 2013
VL 119
IS 16
BP 2981
EP 2989
DI 10.1002/cncr.28141
PG 9
WC Oncology
SC Oncology
GA 194KQ
UT WOS:000322632400009
PM 23674264
ER
PT J
AU Patel, C
Stenke, L
Varma, S
Lindberg, ML
Bjorkholm, M
Sjoberg, J
Viktorsson, K
Lewensohn, R
Landgren, O
Gottesman, MM
Gillet, JP
AF Patel, Chirayu
Stenke, Leif
Varma, Sudhir
Lindberg, Marita Lagergren
Bjorkholm, Magnus
Sjoberg, Jan
Viktorsson, Kristina
Lewensohn, Rolf
Landgren, Ola
Gottesman, Michael M.
Gillet, Jean-Pierre
TI Multidrug resistance in relapsed acute myeloid leukemia: Evidence of
biological heterogeneity
SO CANCER
LA English
DT Article
DE acute myeloid leukemia; acquired drug resistance; therapy-related drug
resistance; multidrug resistance; leukemia cell lines
ID P-GLYCOPROTEIN; EXPRESSION; CANCER; AML; TRANSPORTERS; CHEMOTHERAPY
AB BACKGROUND: Studies of mechanisms mediating resistance to chemotherapy led to the discovery of the multidrug transporter ABCB1 (ATP-binding cassette, subfamily B, member 1), often expressed in leukemic cells of patients with acute myeloid leukemia (AML). Most clinical trials evaluating the strategy of inhibiting efflux-mediated chemotherapeutic resistance have been unsuccessful, clearly indicating the need for a better approach. METHODS: This study investigated the clinical relevance of 380 genes whose expression has been shown to affect the response to chemotherapy, mostly through in vitro studies, in 11 paired samples obtained at AML diagnosis and at relapse. The expression profiling of these 380 genes was performed using TaqMan-based quantitative reverse-transcription polymerase chain reaction. Patients had a median age of 58 years at diagnosis, a median duration of complete remission of 284.5 days, and a median overall survival of 563 days. Cytogenetic abnormalities were detected at diagnosis in 4 patients, whereas 5 displayed a normal karyotype and 2 were not investigated. RESULTS: Hierarchical clustering shows that samples taken at diagnosis and relapse clustered in pairs for 6 patients of the 11 studied, suggesting recurrence of the same leukemic blast, whereas for the other 5 patients, the data indicate their relapse blasts arose from different origins. A patient-by-patient analysis of the paired samples led to the striking observation that each had a unique gene signature representing different mechanisms of resistance. CONCLUSIONS: The data underline the need for personalized molecular analysis to tailor treatment for patients with AML. Cancer 2013; 119: 3076-83. (C) 2013 American Cancer Society.
C1 [Patel, Chirayu; Gottesman, Michael M.; Gillet, Jean-Pierre] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Patel, Chirayu] HHMI NIH Res Scholars Program, Bethesda, MD USA.
[Stenke, Leif; Lindberg, Marita Lagergren; Bjorkholm, Magnus] Karolinska Inst, Dept Med, Stockholm, Sweden.
[Stenke, Leif; Lindberg, Marita Lagergren; Bjorkholm, Magnus; Sjoberg, Jan; Viktorsson, Kristina; Lewensohn, Rolf] St Gorans Univ Hosp, S-11281 Stockholm, Sweden.
[Stenke, Leif; Lindberg, Marita Lagergren; Sjoberg, Jan; Viktorsson, Kristina; Lewensohn, Rolf] Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.
[Varma, Sudhir] NIAID, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, Off Sci Management & Operat,NIH, Bethesda, MD 20892 USA.
[Landgren, Ola] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA.
RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, NIH, 37 Convent Dr,Room 2108, Bethesda, MD 20892 USA.
EM mgottesman@nih.gov
RI Varma, Sudhir/N-8763-2014
OI Varma, Sudhir/0000-0002-4096-4782
FU HHMI-NIH Research Scholars Program; Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research; Swedish National Board of Health and Welfare; Adolf H.
Lundin Charitable Foundation
FX The HHMI-NIH Research Scholars Program supported the research training
of Chirayu Patel. This work was supported by the Intramural Research
Program of the National Institutes of Health, National Cancer Institute,
Center for Cancer Research; the Swedish National Board of Health and
Welfare; and the Adolf H. Lundin Charitable Foundation.
NR 24
TC 12
Z9 12
U1 1
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
EI 1097-0142
J9 CANCER-AM CANCER SOC
JI Cancer
PD AUG 15
PY 2013
VL 119
IS 16
BP 3076
EP 3083
DI 10.1002/cncr.28098
PG 8
WC Oncology
SC Oncology
GA 194KQ
UT WOS:000322632400021
PM 23674237
ER
PT J
AU Chow, WH
Linehan, WM
Devesa, SS
AF Chow, Wong-Ho
Linehan, W. Marston
Devesa, Susan S.
TI Reply to Racial disparity in renal cell carcinoma patient survival
according to demographic and clinical characteristics
SO CANCER
LA English
DT Letter
C1 [Chow, Wong-Ho] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[Linehan, W. Marston] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Devesa, Susan S.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Chow, WH (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
FU Intramural NIH HHS
NR 3
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD AUG 15
PY 2013
VL 119
IS 16
BP 3101
EP 3101
DI 10.1002/cncr.28125
PG 1
WC Oncology
SC Oncology
GA 194KQ
UT WOS:000322632400025
PM 23695994
ER
PT J
AU Tamma, PD
Powers, JH
AF Tamma, Pranita D.
Powers, John H.
TI Do Patient Data Really Support the Clinical and Laboratory Standards
Institute Recommendation for Lowering Third-Generation Cephalosporin
Interpretive Breakpoints?
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Letter
ID PSEUDOMONAS-AERUGINOSA; PIPERACILLIN-TAZOBACTAM; STAPHYLOCOCCUS-AUREUS;
BACTEREMIA; OUTCOMES; ENTEROBACTERIACEAE; INFECTIONS; CEFEPIME
C1 [Tamma, Pranita D.] Johns Hopkins Med Inst, Div Pediat Infect Dis, Dept Pediat, Baltimore, MD 21287 USA.
[Powers, John H.] NIAID, Div Clin Res, NIH, Bethesda, MD 20892 USA.
RP Tamma, PD (reprint author), Johns Hopkins Med Inst, Div Pediat Infect Dis, Dept Pediat, 200 N Wolfe St,Ste 3155, Baltimore, MD 21287 USA.
EM ptamma1@jhmi.edu
NR 12
TC 4
Z9 4
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD AUG 15
PY 2013
VL 57
IS 4
BP 624
EP U275
DI 10.1093/cid/cit308
PG 2
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 190LV
UT WOS:000322342500034
PM 23658433
ER
PT J
AU Klase, Z
Jeang, KT
AF Klase, Zachary
Jeang, Kuan-Teh
TI Reciprocal functional pseudotyping of HIV-1 and HTLV-1 viral genomes by
the heterologous counterpart envelope proteins
SO VIROLOGY
LA English
DT Article
DE HIV-1; HTLV-1; Pseudotyping; Chimera
ID IMMUNODEFICIENCY-VIRUS TYPE-1; CELL LYMPHOTROPIC VIRUS; HEPATITIS-C
VIRUS; GLUCOSE-TRANSPORTER GLUT-1; MURINE LEUKEMIA-VIRUS; CD4
DOWN-MODULATION; SUPERINFECTION EXCLUSION; T-CELLS; SUPER-INFECTION; I
INFECTION
AB HIV-1 and HTLV-1 can infect CD4+ T cells and can co-infect the same individual. In principle, it is possible that both viruses can infect the same CD4+ T cells in dually infected persons. Currently, how efficiently HTLV-1 and HIV-1 co-infects the same cell and the full extent of their biological interactions are not well-understood. Here, we report evidence confirming that both viruses can infect the same cells and that HTLV-1 envelope (Env) can pseudotype HIV-1 viral particles and HIV-1 envelope (Env) can pseudotype HTLV-1 virions to mediate subsequent infections of substrate cells. We also show that the construction of a chimeric HTLV-1 molecular clone carrying the HIV-1 Env in place of its HTLV-1 counterpart results in a replication competent moiety. These findings raise new implications of viral complementation and assortment between HIV-1 and HTLV-1 in dually infected persons. Published by Elsevier Inc.
C1 [Klase, Zachary; Jeang, Kuan-Teh] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
RP Klase, Z (reprint author), NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
EM klaseza@niaid.nih.gov
FU Intramural NIH HHS [Z99 AI999999]
NR 47
TC 0
Z9 0
U1 1
U2 7
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD AUG 15
PY 2013
VL 443
IS 1
BP 106
EP 112
DI 10.1016/j.virol.2013.04.027
PG 7
WC Virology
SC Virology
GA 189SZ
UT WOS:000322289900012
PM 23747197
ER
PT J
AU Chess, DJ
Billings, E
Covian, R
Glancy, B
French, S
Taylor, J
de Bari, H
Murphy, E
Balaban, RS
AF Chess, David J.
Billings, Eric
Covian, Raul
Glancy, Brian
French, Stephanie
Taylor, Joni
de Bari, Heather
Murphy, Elizabeth
Balaban, Robert S.
TI Optical spectroscopy in turbid media using an integrating sphere:
Mitochondrial chromophore analysis during metabolic transitions
SO ANALYTICAL BIOCHEMISTRY
LA English
DT Article
DE Mitochondria; Spectroscopy; Electron transport chain;
Ischemia/reperfusion
ID CYTOCHROME-C-OXIDASE; OXIDATIVE-PHOSPHORYLATION SYSTEM; ISOLATED CARDIAC
MYOCYTES; ELECTRON-TRANSPORT CHAIN; RAT-LIVER MITOCHONDRIA;
RESPIRATORY-CHAIN; IN-VIVO; IRREVERSIBLE-PROCESSES; RECIPROCAL
RELATIONS; KINETIC-ANALYSIS
AB Recent evidence suggests that the activity of mitochondrial oxidative phosphorylation complexes (MOPCs) is modulated at multiple sites. Here, a method of optically monitoring electron distribution within and between MOPCs is described using a center-mounted sample in an integrating sphere (to minimize scattering effects) with a rapid-scanning spectrometer. The redox-sensitive MOPC absorbances (similar to 465-630 nm) were modeled using linear least squares analysis with individual chromophore spectra. Classical mitochondrial activity transitions (e.g., ADP-induced increase in oxygen consumption) were used to characterize this approach. Most notable in these studies was the observation that intermediates of the catalytic cycle of cytochrome oxidase are dynamically modulated with metabolic state. The MOPC redox state, along with measurements of oxygen consumption and mitochondrial membrane potential, was used to evaluate the conductances of different sections of the electron transport chain. This analysis then was applied to mitochondria isolated from rabbit hearts subjected to ischemia/reperfusion (I/R). Surprisingly, I/R resulted in an inhibition of all measured MOPC conductances, suggesting a coordinated down-regulation of mitochondrial activity with this well-established cardiac perturbation. Published by Elsevier Inc.
C1 [Chess, David J.; Billings, Eric; Covian, Raul; Glancy, Brian; French, Stephanie; Taylor, Joni; de Bari, Heather; Balaban, Robert S.] NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA.
[Murphy, Elizabeth] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA.
RP Chess, DJ (reprint author), NHLBI, Cardiac Energet Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM chessdj@mail.nih.gov
RI Glancy, Brian/P-3163-2016
OI Glancy, Brian/0000-0002-8571-244X
FU National Institutes of Health (NIH)
FX Research was supported by the National Institutes of Health (NIH)
Intramural Research Program.
NR 67
TC 5
Z9 5
U1 0
U2 7
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0003-2697
EI 1096-0309
J9 ANAL BIOCHEM
JI Anal. Biochem.
PD AUG 15
PY 2013
VL 439
IS 2
BP 161
EP 172
DI 10.1016/j.ab.2013.04.017
PG 12
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 189RV
UT WOS:000322286900013
PM 23665273
ER
PT J
AU Roy-Engel, AM
Moss, T
Maraia, RJ
AF Roy-Engel, Astrid M.
Moss, Thomas
Maraia, Richard J.
TI Meeting report for Odd Pols 2012
SO GENE
LA English
DT Article
AB The Eighth International Biennial Conference on RNA polymerases land III (the 'Odd Pols') was held June 7-11, 2012 at The Airlie Center in Warrenton Virginia, USA. It was sponsored by the Universite Laval and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, and organized by Rich Maraia and Tom Moss. The meeting honored the memory of Pierre Thuriaux (Jan 1, 1950-March 18, 2012) and David Schneider reminisced on the important accomplishments his mentor Masayasu Nomura (1927-2011). The goal of the conference was to bring together the world's experts on RNA polymerase I and RNA polymerase III to highlight and share their latest results and varied experimental approaches. The meeting drew attendees from twelve countries and most contributed through oral and poster presentations. The talks were organized into several sessions subdivided into 10 distinct topics. The keynote speaker, Ian Willis, opened the meeting with his presentation entitled "New Regulators of Signaling to Odd Pols" and the closing presentation was given by Patrick Cramer with his presentation "Conservation of the RNA polymerase I, II and III transcription initiation machineries". Here we present some of the highlights from the meeting using summaries provided by the participants. (C) 2013 Elsevier B.V. All rights reserved.
C1 [Roy-Engel, Astrid M.] Tuane Canc Ctr, Dept Epidemiol, New Orleans, LA 70112 USA.
[Roy-Engel, Astrid M.] Louisiana Canc Res Consortium, New Orleans, LA 70112 USA.
[Moss, Thomas] Univ Laval, Hotel Dieu Quebec, Canc Res Ctr, Quebec City, PQ G1R 2J6, Canada.
[Moss, Thomas] Univ Laval, Hotel Dieu Quebec, Dept Med Biol Med Biochem & Pathol, Quebec City, PQ G1R 2J6, Canada.
[Maraia, Richard J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Intramural Res Program Genom Dfferentiat, NIH, Bethesda, MD USA.
[Maraia, Richard J.] US PHS, Commissioned Corps, Rockville, MD USA.
RP Roy-Engel, AM (reprint author), Tuane Canc Ctr, Dept Epidemiol, 1430 Tulane Ave,SL-66, New Orleans, LA 70112 USA.
EM aengel@tulane.edu
OI Engel, Astrid/0000-0002-8884-4544
FU National Institutes of Health (NIH) [P20GM103518/P20RR020152,
R01GM079709A]; Intramural Research Program of the Eunice Kennedy Shriver
National Institute of Child Health and Human Development, NIH; Cancer
Research Society (CRS/SRC); Canadian Institutes of Health Research
(CIHR) [MOP-12205]; Canadian Cancer Society Research Institute (CCSRI)
[2010-700477]
FX The Roy-Engel lab is supported by the National Institutes of Health
(NIH) P20GM103518/P20RR020152 and R01GM079709A; R.J. Maraia is supported
by the Intramural Research Program of the Eunice Kennedy Shriver
National Institute of Child Health and Human Development, NIH. R.J.M. is
a member of the U.S. Public Health Service Commissioned Corps. Tom moss
is supported by operating grants from the Cancer Research Society
(CRS/SRC); the Canadian Institutes of Health Research (CIHR) (grant
#MOP-12205); and the Canadian Cancer Society Research Institute (CCSRI)
(grant # 2010-700477). The contents of this manuscript are solely the
responsibility of the authors and do not necessarily represent the
official views of NIH. We thank the participants of the meeting for
their contribution and their permission to include their research in
this summary. We also wish to apologize to colleagues whose work was not
included.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-1119
J9 GENE
JI Gene
PD AUG 15
PY 2013
VL 526
IS 1
SI SI
BP 1
EP 6
DI 10.1016/j.gene.2013.04.009
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA 193KE
UT WOS:000322557900001
PM 23608169
ER
PT J
AU Demerath, EW
Liu, CT
Franceschini, N
Chen, G
Palmer, JR
Smith, EN
Chen, CTL
Ambrosone, CB
Arnold, AM
Bandera, EV
Berenson, GS
Bernstein, L
Britton, A
Cappola, AR
Carlson, CS
Chanock, SJ
Chen, W
Chen, Z
Deming, SL
Elks, CE
Evans, MK
Gajdos, Z
Henderson, BE
Hu, JJ
Ingles, S
John, EM
Kerr, KF
Kolonel, LN
Le Marchand, L
Lu, XN
Millikan, RC
Musani, SK
Nock, NL
North, K
Nyante, S
Press, MF
Rodriquez-Gil, JL
Ruiz-Narvaez, EA
Schork, NJ
Srinivasan, SR
Woods, NF
Zheng, W
Ziegler, RG
Zonderman, A
Heiss, G
Windham, BG
Wellons, M
Murray, SS
Nalls, M
Pastinen, T
Rajkovic, A
Hirschhorn, J
Cupples, LA
Kooperberg, C
Murabito, JM
Haiman, CA
AF Demerath, Ellen W.
Liu, Ching-Ti
Franceschini, Nora
Chen, Gary
Palmer, Julie R.
Smith, Erin N.
Chen, Christina T. L.
Ambrosone, Christine B.
Arnold, Alice M.
Bandera, Elisa V.
Berenson, Gerald S.
Bernstein, Leslie
Britton, Angela
Cappola, Anne R.
Carlson, Christopher S.
Chanock, Stephen J.
Chen, Wei
Chen, Zhao
Deming, Sandra L.
Elks, Cathy E.
Evans, Michelle K.
Gajdos, Zofia
Henderson, Brian E.
Hu, Jennifer J.
Ingles, Sue
John, Esther M.
Kerr, Kathleen F.
Kolonel, Laurence N.
Le Marchand, Loic
Lu, Xiaoning
Millikan, Robert C.
Musani, Solomon K.
Nock, Nora L.
North, Kari
Nyante, Sarah
Press, Michael F.
Rodriquez-Gil, Jorge L.
Ruiz-Narvaez, Edward A.
Schork, Nicholas J.
Srinivasan, Sathanur R.
Woods, Nancy F.
Zheng, Wei
Ziegler, Regina G.
Zonderman, Alan
Heiss, Gerardo
Windham, B. Gwen
Wellons, Melissa
Murray, Sarah S.
Nalls, Michael
Pastinen, Tomi
Rajkovic, Aleksandar
Hirschhorn, Joel
Cupples, L. Adrienne
Kooperberg, Charles
Murabito, Joanne M.
Haiman, Christopher A.
TI Genome-wide association study of age at menarche in African-American
women
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID BODY-MASS INDEX; NUTRITION EXAMINATION SURVEY; BREAST-CANCER;
POSTMENOPAUSAL WOMEN; SEQUENCE VARIANTS; US GIRLS; TRANSETHNIC
METAANALYSIS; GENETIC ASSOCIATION; NATIONAL-HEALTH; TWIN FAMILIES
AB African-American (AA) women have earlier menarche on average than women of European ancestry (EA), and earlier menarche is a risk factor for obesity and type 2 diabetes among other chronic diseases. Identification of common genetic variants associated with age at menarche has a potential value in pointing to the genetic pathways underlying chronic disease risk, yet comprehensive genome-wide studies of age at menarche are lacking for AA women. In this study, we tested the genome-wide association of self-reported age at menarche with common single-nucleotide polymorphisms (SNPs) in a total of 18 089 AA women in 15 studies using an additive genetic linear regression model, adjusting for year of birth and population stratification, followed by inverse-variance weighted meta-analysis (Stage 1). Top meta-analysis results were then tested in an independent sample of 2850 women (Stage 2). First, while no SNP passed the pre-specified P 5 10(8) threshold for significance in Stage 1, suggestive associations were found for variants near FLRT2 and PIK3R1, and conditional analysis identified two independent SNPs (rs339978 and rs980000) in or near RORA, strengthening the support for this suggestive locus identified in EA women. Secondly, an investigation of SNPs in 42 previously identified menarche loci in EA women demonstrated that 25 (60) of them contained variants significantly associated with menarche in AA women. The findings provide the first evidence of cross-ethnic generalization of menarche loci identified to date, and suggest a number of novel biological links to menarche timing in AA women.
C1 [Demerath, Ellen W.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Liu, Ching-Ti; Lu, Xiaoning; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Palmer, Julie R.; Ruiz-Narvaez, Edward A.] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA.
[Franceschini, Nora; Millikan, Robert C.; Heiss, Gerardo] Univ N Carolina, Dept Epidemiol, Gillings Sch Publ Hlth, Chapel Hill, NC USA.
[North, Kari] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[North, Kari] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA.
[Chen, Gary; Henderson, Brian E.; Ingles, Sue; Haiman, Christopher A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Press, Michael F.] Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA.
[Smith, Erin N.] Univ Calif San Diego, Div Genome Informat Sci, Dept Pediat, La Jolla, CA 92093 USA.
[Murray, Sarah S.] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA.
[Chen, Christina T. L.; Carlson, Christopher S.; Kooperberg, Charles] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Ambrosone, Christine B.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA.
[Arnold, Alice M.; Kerr, Kathleen F.] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA.
[Woods, Nancy F.] Univ Washington, Sch Nursing, Seattle, WA 98195 USA.
[Bandera, Elisa V.] Canc Inst New Jersey, New Brunswick, NJ USA.
[Berenson, Gerald S.; Chen, Wei; Srinivasan, Sathanur R.] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA USA.
[Bernstein, Leslie] Beckman Res Inst, Dept Populat Sci, Div Canc Etiol, Duarte, CA USA.
[Britton, Angela; Nalls, Michael] NIH, Natl Inst Aging, Neurogenet Lab, Bethesda, MD 20892 USA.
[Cappola, Anne R.] Univ Penn, Perelman Sch Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA.
[Evans, Michelle K.] NIH, Natl Inst Aging, Clin Res Branch, Hlth Disparaties Res Sect, Baltimore, MD USA.
[Chanock, Stephen J.; Nyante, Sarah] NIH, NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Ziegler, Regina G.] NCI, Div Canc Epidemiol & Genet, Epidemiol & Biostat Program, Bethesda, MD 20892 USA.
[Chen, Zhao] Univ Arizona, Coll Publ Hlth, Tucson, AZ 85721 USA.
[Deming, Sandra L.; Zheng, Wei] Vanderbilt Epidemiol Ctr, Dept Med, Div Epidemiol, Nashville, TN USA.
[Deming, Sandra L.; Zheng, Wei] Vandebilt Ingram Canc Ctr, Nashville, TN USA.
RP Haiman, CA (reprint author), Univ So Calif, Keck Sch Med, Harlyne Norris Res Tower,1450 Biggy St,Room 1504A, Los Angeles, CA 90033 USA.
EM ewd@umn.edu; clk@fhcrc.org; murabito@bu.edu; haiman@usc.edu
RI Bandera, Elisa/M-4169-2014; Kerr, Kathleen/A-2893-2013;
OI Bandera, Elisa/0000-0002-8789-2755; Murabito,
Joanne/0000-0002-0192-7516; Ruiz-Narvaez, Edward/0000-0002-0339-5824;
Palmer, Julie/0000-0002-6534-335X; Nock, Nora L./0000-0002-6476-6692;
Zonderman, Alan B/0000-0002-6523-4778
FU National Institutes of Health [HHSN268200900055C, 5215810-550000234,
R01-CA100598, 1U54RR025204-01]; National Heart, Lung, and Blood
Institute [HHSN268201100005C, HHSN268 201100006C, HHSN268201100007C,
HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268
201100011C, HHSN268201100012C, R01HL087641, R01HL59367, R01HL086694,
N02-HL-64278]; National Human Genome Research Institute [U01HG004402];
NIH Roadmap for Medical Research Grant [UL1RR025005]; National Heart,
Lung and Blood Institute (NHLBI); University of Alabama at Birmingham,
Coordinating Center [N01-HC-95095]; University of Alabama at Birmingham,
Field Center [N01-HC-48047]; University of Minnesota, Field Center
[N01-HC-48048]; Northwestern University, Field Center [N01-HC-48049];
Kaiser Foundation Research Institute [N01-HC-48050]; Harbor-UCLA
Research and Education Institute [N01-HC-05187]; University of
California, Irvine [N01-HC-45134, N01-HC-95100]; Wake Forest University
[N01-HC-45205]; New England Medical Center [N01-HC-45204]; National
Heart, Lung and Blood Institute [K23-HL-87114, RO1-HL46380,
M01-RR-00080]; National Center on Minority Health and Health Disparities
through National Institutes of Health [N01-HC-95170, N01-HC-95171,
N01-HC-95172]; Department of Defense Breast Cancer Research Program Era
of Hope Scholar Award; Norris Foundation; CARE-National Institute for
Child Health and Development grant [NO1-HD-3-3175]; CBCS - National
Institutes of Health Specialized Program of Research Excellence in
Breast Cancer [P50-CA58223]; Center for Environmental Health and
Susceptibility, National Institute of Environmental Health Sciences,
National Institutes of Health [P30-ES10126]; MEC - National Institutes
of Health [R01-CA63464, R37-CA54281]; NHBS - National Institutes of
Health [R01-CA100374]; NC-BCFR - National Institutes of Health
[U01-CA69417]; SFBCS - National Institutes of Health [R01-CA77305];
United States Army Medical Research Program [DAMD17-96-6071]; National
Cancer Institute, National Institutes of Health [RFA CA-95-011];
National Cancer Institute, National Institutes of Health; WCHS - U.S.
Army Medical Research and Material Command (USAMRMC)
[DAMD-17-01-0-0334]; Breast Cancer Research Foundation; WFBC-National
Institutes of Health [R01-CA73629]; National Institute of Environmental
Health Science [ES-021724]; National Institute of Child Health and Human
Development [HD-061437, HD-062783]; National Institute on Aging
[AG-16592]; National Institute of Health/National Center for Research
Resources [UL1RR025774]; National Cancer Institute, Division of Cancer
Control and Population Science [R01 CA058420, R01 CA098663]; Susan G.
Komen for the Cure Foundation; National Institute of Health, National
Institute on Aging; National Center on Minority Health and Health
Disparities [Z01-AG000513]; National Heart, Lung, and Blood Institute,
National Institutes of Health, U.S. Department of Health and Human
Services [HHSN268201100046C, HHSN268201100001C, HHSN 268201100002C,
HHSN268201100003C, HHSN2682011 00004C, HHSN271201100004C];
[R21AG032598]
FX Nine parent studies contributed parent study data, ancillary study data
and DNA samples through the Massachusetts Institute of Technology-Broad
Institute (N01-HC-65226) to create the Candidate Gene Association
Resource (CARe) genotype/phenotype database for wide dissemination to
the biomedical research community. Of these, four parent studies (ARIC,
CARDIA, CFS and JHS) participated in this study of age at menarche.
Analysis support came through National Institutes of Health
(HHSN268200900055C and 5215810-550000234). Additional support for this
menarche project came from R21AG032598. Information on the CARe parent
studies follows here. The Atherosclerosis Risk in Communities Study
(ARIC) is carried out as a collaborative study supported by National
Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268
201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C,
HHSN268201100010C, HHSN268 201100011C, and HHSN268201100012C),
(R01HL087641), (R01HL59367 and R01HL086694); National Human Genome
Research Institute (U01HG004402); and National Institutes of Health
contract (HHSN268200625226C). Infrastructure was partly supported by a
component of the National Institutes of Health and NIH Roadmap for
Medical Research Grant (UL1RR025005). Coronary Artery Risk in Young
Adults (CARDIA): Work on this manuscript was supported (or partially
supported) by contracts from the National Heart, Lung and Blood
Institute (NHLBI): University of Alabama at Birmingham, Coordinating
Center (N01-HC-95095); University of Alabama at Birmingham, Field Center
(N01-HC-48047); University of Minnesota, Field Center (N01-HC-48048);
Northwestern University, Field Center (N01-HC-48049); Kaiser Foundation
Research Institute (N01-HC-48050); Harbor-UCLA Research and Education
Institute (N01-HC-05187), University of California, Irvine
(N01-HC-45134, N01-HC-95100); Wake Forest University (Year 20 Exam)
(N01-HC-45205); New England Medical Center (Year 20 Exam)
(N01-HC-45204). M.W.'s effort is supported by the National Heart, Lung
and Blood Institute (K23-HL-87114). Cleveland Family Study (CFS): The
Cleveland Family Study was supported by the National Heart, Lung and
Blood Institute (RO1-HL46380, M01-RR-00080). Jackson Heart Study (JHS):
The Jackson Heart Study is supported by the National Heart, Lung, and
Blood Institute and the National Center on Minority Health and Health
Disparities through National Institutes of Health contracts
(N01-HC-95170, N01-HC-95171 and N01-HC-95172).; AABC Studies (CARE,
CBCS, MEC, NBHS, NC-BCFR/SFBCS, PLCO, WCHS, WFBC): This work was
supported by a Department of Defense Breast Cancer Research Program Era
of Hope Scholar Award to C. A. H. and the Norris Foundation. Each of the
participating studies was supported by the following grants:
CARE-National Institute for Child Health and Development grant
(NO1-HD-3-3175), CBCS - National Institutes of Health Specialized
Program of Research Excellence in Breast Cancer (P50-CA58223) and Center
for Environmental Health and Susceptibility, National Institute of
Environmental Health Sciences, National Institutes of Health, grant
(P30-ES10126); MEC - National Institutes of Health grants (R01-CA63464
and R37-CA54281); NHBS - National Institutes of Health grant
(R01-CA100374); NC-BCFR - National Institutes of Health grant
(U01-CA69417). SFBCS - National Institutes of Health grant (R01-CA77305)
and United States Army Medical Research Program grant (DAMD17-96-6071).
The Breast Cancer Family Registry (BCFR) was supported by the National
Cancer Institute, National Institutes of Health (RFA CA-95-011) and
through cooperative agreements with members of the Breast Cancer Family
Registry and Principal Investigators; PLCO Intramural Research Program,
National Cancer Institute, National Institutes of Health; WCHS - U.S.
Army Medical Research and Material Command (USAMRMC) grant
(DAMD-17-01-0-0334), the National Institutes of Health grant
(R01-CA100598) and the Breast Cancer Research Foundation; and
WFBC-National Institutes of Health grant (R01-CA73629).; Bogalusa Heart
Study (BHS): E.N.S., N.J.S. and S. S. M. are supported in part by
National Institutes of Health (grant 1U54RR025204-01). W. C., S. R. S.
and G. S. B. are supported from National Institute of Environmental
Health Science (ES-021724); from the National Institute of Child Health
and Human Development (HD-061437 and HD-062783) and from the National
Institute on Aging (AG-16592). E.N.S., S. S. M. and N.J.S. are supported
in part by National Institute of Health/National Center for Research
Resources Grant (UL1RR025774).; Black Women's Health Study (BWHS): BWHS.
research was supported from the National Cancer Institute, Division of
Cancer Control and Population Science (R01 CA058420 and R01 CA098663);
and by a grant from the Susan G. Komen for the Cure Foundation.; Health
Across the Lifespan (HANDLS): This research was supported by the
Intramural Research Program of the National Institute of Health,
National Institute on Aging and the National Center on Minority Health
and Health Disparities (Z01-AG000513) and human subjects protocol (#
2009-149).; Women's Health Initiative (WHI): The WHI program is
supported by the National Heart, Lung, and Blood Institute, National
Institutes of Health, U.S. Department of Health and Human Services
(HHSN268201100046C, HHSN268201100001C, HHSN 268201100002C,
HHSN268201100003C, HHSN2682011 00004C and HHSN271201100004C). Funding
for WHI SHARe genotyping was provided by the National Heart, Lung, and
Blood Institute Contract (N02-HL-64278).
NR 86
TC 11
Z9 11
U1 4
U2 20
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD AUG 15
PY 2013
VL 22
IS 16
BP 3329
EP 3346
DI 10.1093/hmg/ddt181
PG 18
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 190LK
UT WOS:000322341300014
PM 23599027
ER
PT J
AU Reiner, AP
Hartiala, J
Zeller, T
Bis, JC
Dupuis, J
Fornage, M
Baumert, J
Kleber, ME
Wild, PS
Baldus, S
Bielinski, SJ
Fontes, JD
Illig, T
Keating, BJ
Lange, LA
Ojeda, F
Muller-Nurasyid, M
Munzel, TF
Psaty, BM
Rice, K
Rotter, JI
Schnabel, RB
Tang, WHW
Thorand, B
Erdmann, J
Jacobs, DR
Wilson, JG
Koenig, W
Tracy, RP
Blankenberg, S
Marz, W
Gross, MD
Benjamin, EJ
Hazen, SL
Allayee, H
AF Reiner, Alexander P.
Hartiala, Jaana
Zeller, Tanja
Bis, Joshua C.
Dupuis, Josee
Fornage, Myriam
Baumert, Jens
Kleber, Marcus E.
Wild, Philipp S.
Baldus, Stephan
Bielinski, Suzette J.
Fontes, Joao D.
Illig, Thomas
Keating, Brendan J.
Lange, Leslie A.
Ojeda, Francisco
Mueller-Nurasyid, Martina
Munzel, Thomas F.
Psaty, Bruce M.
Rice, Kenneth
Rotter, Jerome I.
Schnabel, Renate B.
Tang, W. H. Wilson
Thorand, Barbara
Erdmann, Jeanette
Jacobs, David R., Jr.
Wilson, James G.
Koenig, Wolfgang
Tracy, Russell P.
Blankenberg, Stefan
Maerz, Winfried
Gross, Myron D.
Benjamin, Emelia J.
Hazen, Stanley L.
Allayee, Hooman
CA CARDIoGRAM Consortium
TI Genome-wide and gene-centric analyses of circulating myeloperoxidase
levels in the charge and care consortia
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID CORONARY-ARTERY-DISEASE; HIGH-DENSITY-LIPOPROTEIN; MACULAR DEGENERATION;
SUSCEPTIBILITY LOCI; CARDIOVASCULAR-DISEASE; PROGNOSTIC VALUE;
ASSOCIATION; COMPLEMENT; RISK; POLYMORPHISM
AB Increased systemic levels of myeloperoxidase (MPO) are associated with the risk of coronary artery disease (CAD). To identify the genetic factors that are associated with circulating MPO levels, we carried out a genome-wide association study (GWAS) and a gene-centric analysis in subjects of European ancestry and African Americans (AAs). A locus on chromosome 1q31.1 containing the complement factor H (CFH) gene was strongly associated with serum MPO levels in 9305 subjects of European ancestry (lead SNP rs800292; P 4.89 10(41)) and in 1690 AA subjects (rs505102; P 1.05 10(8)). Gene-centric analyses in 8335 subjects of European ancestry additionally identified two rare MPO coding sequence variants that were associated with serum MPO levels (rs28730837, P 5.21 10(12); rs35897051, P 3.32 10(8)). A GWAS for plasma MPO levels in 9260 European ancestry subjects identified a chromosome 17q22 region near MPO that was significantly associated (lead SNP rs6503905; P 2.94 10(12)), but the CFH locus did not exhibit evidence of association with plasma MPO levels. Functional analyses revealed that rs800292 was associated with levels of complement proteins in serum. Variants at chromosome 17q22 also had pleiotropic cis effects on gene expression. In a casecontrol analysis of 80 000 subjects from CARDIoGRAM, none of the identified single-nucleotide polymorphisms (SNPs) were associated with CAD. These results suggest that distinct genetic factors regulate serum and plasma MPO levels, which may have relevance for various acute and chronic inflammatory disorders. The clinical implications for CAD and a better understanding of the functional basis for the association of CFH and MPO variants with circulating MPO levels require further study.
C1 [Reiner, Alexander P.; Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Bis, Joshua C.; Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Bis, Joshua C.; Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Rice, Kenneth] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Hartiala, Jaana; Allayee, Hooman] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Hartiala, Jaana; Allayee, Hooman] Univ So Calif, Keck Sch Med, Inst Med Genet, Los Angeles, CA 90033 USA.
[Zeller, Tanja; Baldus, Stephan; Ojeda, Francisco; Schnabel, Renate B.; Blankenberg, Stefan] Univ Heart Ctr Hamburg, Dept Gen & Intervent Cardiol, Hamburg, Germany.
[Dupuis, Josee; Fontes, Joao D.; Benjamin, Emelia J.] NHLBI, Framingham, MA USA.
[Dupuis, Josee; Fontes, Joao D.; Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Framingham, MA USA.
[Dupuis, Josee] Boston Univ, Sch Med, Dept Biostat, Boston, MA 02118 USA.
[Fontes, Joao D.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Epidemiol, Boston, MA 02118 USA.
[Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Brown Fdn Inst Mol Med, Houston, TX 77030 USA.
[Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Div Epidemiol, Sch Publ Hlth, Houston, TX 77030 USA.
[Baumert, Jens; Thorand, Barbara] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.
[Illig, Thomas] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany.
[Mueller-Nurasyid, Martina] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany.
[Kleber, Marcus E.] LURIC Study Non Profit LLC, Freiburg, Germany.
[Kleber, Marcus E.; Maerz, Winfried] Heidelberg Univ, Mannheim Med Fac, Dept Publ Hlth Social & Prevent Med, Mannheim, Germany.
[Wild, Philipp S.; Munzel, Thomas F.] Johannes Gutenberg Univ Mainz, Dept Med 2, Univ Med Ctr, D-55122 Mainz, Germany.
[Wild, Philipp S.; Munzel, Thomas F.] Johannes Gutenberg Univ Mainz, Ctr Thrombosis & Haemostasis, D-55122 Mainz, Germany.
[Bielinski, Suzette J.] Mayo Clin, Coll Med, Dept Hlth Sci Res, Div Epidemiol, Rochester, MN USA.
[Illig, Thomas] Hannover Med Sch, Hannover Unified Biobank, Hannover, Germany.
[Keating, Brendan J.] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA.
[Keating, Brendan J.] Childrens Hosp Philadelphia, Div Human Genet, Abramson Res Ctr, Philadelphia, PA 19104 USA.
[Keating, Brendan J.] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA.
[Lange, Leslie A.] Univ N Carolina, Sch Med, Dept Genet, Chapel Hill, NC USA.
[Mueller-Nurasyid, Martina] Univ Hosp Grosshadern, Dept Med 1, Munich, Germany.
[Mueller-Nurasyid, Martina] Univ Munich, Chair Epidemiol, Munich, Germany.
[Mueller-Nurasyid, Martina] Univ Munich, Chair Genet Epidemiol, Munich, Germany.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98121 USA.
[Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Tang, W. H. Wilson; Hazen, Stanley L.] Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44106 USA.
[Tang, W. H. Wilson; Hazen, Stanley L.] Cleveland Clin, Ctr Cardiovasc Diagnost & Prevent, Cleveland, OH 44106 USA.
[Erdmann, Jeanette] Med Univ Lubeck, Med Klin 2, D-23538 Lubeck, Germany.
[Erdmann, Jeanette] Med Univ Lubeck, Deutsch Zentrum Herz Kreislaufforsch eV DZHK, D-23538 Lubeck, Germany.
[Jacobs, David R., Jr.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
[Koenig, Wolfgang] Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, D-89069 Ulm, Germany.
[Tracy, Russell P.] Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA.
[Tracy, Russell P.] Univ Vermont, Coll Med, Dept Biochem, Burlington, VT 05405 USA.
[Maerz, Winfried] Synlab Ctr Lab Diagnost, Heidelberg, Germany.
[Gross, Myron D.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
RP Allayee, H (reprint author), Univ So Calif, Keck Sch Med, Inst Med Genet, 2250 Alcazar St,CSC202, Los Angeles, CA 90033 USA.
EM hallayee@usc.edu
RI Erdmann, Jeanette/P-7513-2014; Tang, Wai Hong/I-1238-2013; Altshuler,
David/A-4476-2009; Thorand, Barbara/B-5349-2014; Schreiber,
Stefan/B-6748-2008; Schnabel, Renate/F-6527-2014; Deloukas,
Panos/B-2922-2013; Willenborg, Christina/D-2668-2012; Boehm,
Bernhard/F-8750-2015; Gudnason, Vilmundur/K-6885-2015; Meitinger,
Thomas/O-1318-2015; Bielinski, Suzette/A-2238-2009
OI Erdmann, Jeanette/0000-0002-4486-6231; Dupuis,
Josee/0000-0003-2871-3603; Benjamin, Emelia/0000-0003-4076-2336;
Ziegler, Andreas/0000-0002-8386-5397; Kleber,
Marcus/0000-0003-0663-7275; Altshuler, David/0000-0002-7250-4107;
Thorand, Barbara/0000-0002-8416-6440; Schreiber,
Stefan/0000-0003-2254-7771; Deloukas, Panos/0000-0001-9251-070X;
Willenborg, Christina/0000-0001-5217-6882; Gudnason,
Vilmundur/0000-0001-5696-0084; Bielinski, Suzette/0000-0002-2905-5430
FU NHLBI [P01HL098055, P01HL076491, R01HL103866, P20HL113452, R01HL103931,
N01-HC-85239, N01-HC-85079, N01-HC-85086, N01-HC-35129, N01 HC-15103,
N01 HC-55222, N01-HC-75150, N01-HC-45133]; NINDS [NS17950]; NIA
[AG-023629, AG-15928, AG-20098, AG-027058, AG08122, AG16495, AG028321];
National Center of Advancing Translational Technologies CTSI grant
[UL1TR000124]; NIDDK [DK063491]; NHGRI [U01HG004402]; NIH
[HHSN268200625226C]; Affymetrix, Inc [N02-HL-6-4278]; National Human
Genome Research Institute [U01-HG-004729, U01-HG-004446, U01-HG-004424];
NIEHS [R01ES021801]; Helmholtz Zentrum Munchen; German Research Center
for Environmental Health, Neuherberg, Germany; German Federal Ministry
of Education and Research (BMBF); German National Genome Research
Network (NGFNPlus) [01GS0834]; University of Ulm; Munich Center of
Health Sciences (MC Health); government of Rheinland-Pflaz [AZ
961-386261/733]; research program 'Wissen schafft Zuknunft';
'Schwerpunkt Vaskulare Pravention' of the Johannes Gutenberg University
of Mainz; Boehringer Ingelheim; PHILIPS medical systems; GHS; National
Genome Network 'NGFNplus'; Federal Ministry of Education and Research,
Germany [01GS0833, 01GS0831]; Agence Nationale de la Recherche, France
[ANR 09 GENO 106 01]; European Community [201668]; National Heart, Lung,
Blood Institute [HHSN268201200036C, HL080295, HL087652, HL105756,
N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020,
N01-HC-55021, N01-HC-55022, HL087641, N01-HC-25195, HL64753, HL076784,
NO1-HC-48047, NO1-HC-48048, NO1-HC-48049, NO1-HC-48050, NO1-HC-95095];
[R01HL71862]
FX The Cleveland Clinic GeneBank study is supported by NHLBI grants
P01HL098055, P01HL076491, R01HL103866, P20HL113452 and R01HL103931. The
Cardiovascular Health Study (CHS) was supported by NHLBI contracts
N01-HC-85239, N01-HC-85079 through N01-HC-85086; N01-HC-35129, N01
HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, HHSN268201200036C
and NHLBI grants HL080295, HL087652, HL105756 with additional
contribution from NINDS. Additional support was provided through
AG-023629, AG-15928, AG-20098, and AG-027058 from the NIA. See also
http://www.chs-nhlbi.org/pi.htm. Additional support was provided by
R01HL71862. DNA handling and genotyping were supported in part by
National Center of Advancing Translational Technologies CTSI grant
UL1TR000124 and NIDDK grant DK063491 to the Southern California Diabetes
Endocrinology Research Center. [CARe: NHLBI contract HHSN268200960009C].
The Atherosclerosis Risk in Communities Study is carried out as a
collaborative study supported by NHLBI contracts N01-HC-55015,
N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021,
N01-HC-55022 and grant HL087641, NHGRI contract U01HG004402 and NIH
contract HHSN268200625226C. The Framingham Heart Study is supported by
NHLBI contract N01-HC-25195) and Affymetrix, Inc contract N02-HL-6-4278
(for genotyping services), and by grants from NHLBI (HL64753; HL076784),
NINDS (NS17950) and NIA (AG08122, AG16495, AG028321. The CARDIA study is
supported by NHLBI contracts NO1-HC-48047, NO1-HC-48048, NO1-HC-48049,
NO1-HC-48050 and NO1-HC-95095. Genotyping and statistical analyses of
the CARDIA white participants were supported by grants U01-HG-004729,
U01-HG-004446 and U01-HG-004424 from the National Human Genome Research
Institute. H. A. was supported by R01ES021801 from NIEHS. The
MONICA/KORA Augsburg studies were financed by the Helmholtz Zentrum
Munchen, German Research Center for Environmental Health, Neuherberg,
Germany and supported by grants from the German Federal Ministry of
Education and Research (BMBF). Part of this work was financed by the
German National Genome Research Network (NGFNPlus, project number
01GS0834) and through additional funds from the University of Ulm.
Furthermore, the research was supported within the Munich Center of
Health Sciences (MC Health) as part of the Ludwig Maximilians University
(LMU) innovative. The Gutenberg Health study (GHS) is funded through the
government of Rheinland-Pflaz (No. AZ 961-386261/733), the research
program 'Wissen schafft Zuknunft' and the 'Schwerpunkt Vaskulare
Pravention' of the Johannes Gutenberg University of Mainz and its
contract with Boehringer Ingelheim and PHILIPS medical systems,
including an unrestricted grant for the GHS. This project has also been
supported by the National Genome Network 'NGFNplus' by the Federal
Ministry of Education and Research, Germany (No. 01GS0833 and 01GS0831,
projects A3/D1), and by joint funding from the Agence Nationale de la
Recherche, France (contract ANR 09 GENO 106 01) and from the Federal
Ministry of Education and Research, Germany. LURIChas received funding
from the European Community's Seventh Framework Programme
(FP7/2007-2013) under grant agreement No. 201668; AtheroRemo.
NR 50
TC 7
Z9 7
U1 0
U2 15
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD AUG 15
PY 2013
VL 22
IS 16
BP 3381
EP 3393
DI 10.1093/hmg/ddt189
PG 13
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 190LK
UT WOS:000322341300018
PM 23620142
ER
PT J
AU Morrison, VA
Oxman, MN
Levin, MJ
Schmader, KE
Guatelli, JC
Betts, RF
Gelb, LD
Pachucki, CT
Keay, SK
Menzies, B
Griffin, MR
Kauffman, CA
Marques, AR
Toney, JF
Simberkoff, MS
Serrao, R
Arbeit, RD
Gnann, JW
Greenberg, RN
Holodniy, M
Keitel, WA
Yeh, SS
Davis, LE
Crawford, GE
Neuzil, KM
Johnson, GR
Zhang, JH
Harbecke, R
Chan, ISF
Keller, PM
Williams, HM
Boardman, KD
Silber, JL
Annunziato, PW
AF Morrison, Vicki A.
Oxman, Michael N.
Levin, Myron J.
Schmader, Kenneth E.
Guatelli, John C.
Betts, Robert F.
Gelb, Larry D.
Pachucki, Constance T.
Keay, Susan K.
Menzies, Barbara
Griffin, Marie R.
Kauffman, Carol A.
Marques, Adriana R.
Toney, John F.
Simberkoff, Michael S.
Serrao, Richard
Arbeit, Robert D.
Gnann, John W.
Greenberg, Richard N.
Holodniy, Mark
Keitel, Wendy A.
Yeh, Shingshing S.
Davis, Larry E.
Crawford, George E.
Neuzil, Kathy M.
Johnson, Gary R.
Zhang, Jane H.
Harbecke, Rith
Chan, Ivan S. F.
Keller, Paul M.
Williams, Heather M.
Boardman, Kathy D.
Silber, Jeffrey L.
Annunziato, Paula W.
CA Shingles Prevention Study Grp
TI Safety of Zoster Vaccine in Elderly Adults Following Documented Herpes
Zoster
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE zoster vaccine; herpes zoster; zoster vaccine safety; zoster vaccine in
elderly persons; ACIP recommendations
ID IMMUNE-RESPONSES; VIRUS; TRIAL
AB After completion of the Shingles Prevention Study (SPS; Department of Veterans Affairs Cooperative Studies Program Number 403), SPS participants who had initially received placebo were offered investigational zoster vaccine without charge. This provided an opportunity to determine the relative safety of zoster vaccine in older adults following documented herpes zoster (HZ).
Methods. A total of 13 681 SPS placebo recipients who elected to receive zoster vaccine were followed for serious adverse events (SAE) for 28 days after vaccination. In contrast to the SPS, a prior episode of HZ was not a contraindication to receiving zoster vaccine. The SPS placebo recipients who received zoster vaccine included 420 who had developed documented HZ during the SPS.
Results. The mean interval between the onset of HZ and the receipt of zoster vaccine in the 420 recipients with prior HZ was 3.61 years (median interval, 3.77 years [range, 3-85 months]); the interval was <5 years for approximately 80% of recipients. The proportion of vaccinated SPS placebo recipients with prior HZ who developed >= 1 SAE (0.95%) was not significantly different from that of vaccinated SPS placebo recipients with no prior history of HZ (0.66%), and the distribution of SAEs in the 2 groups was comparable.
Conclusions. These results demonstrate that the general safety of zoster vaccine in older persons is not altered by a recent history of documented HZ, supporting the safety aspect of the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices recommendation to administer zoster vaccine to all persons >= 60 years of age with no contraindications, regardless of a prior history of HZ.
C1 [Morrison, Vicki A.] Vet Affairs Med Ctr, Minneapolis, MN USA.
[Morrison, Vicki A.] Univ Minnesota, Minneapolis, MN USA.
[Oxman, Michael N.; Guatelli, John C.; Harbecke, Rith; Williams, Heather M.] Vet Affairs San Diego Healthcare Syst, San Diego, CA USA.
[Oxman, Michael N.; Guatelli, John C.; Harbecke, Rith; Williams, Heather M.] Univ Calif San Diego, San Diego, CA 92103 USA.
[Levin, Myron J.] Univ Colorado Denver, Denver, CO USA.
[Schmader, Kenneth E.] Durham Vet Affairs Med Ctr, GRECC, Durham, NC USA.
[Schmader, Kenneth E.] Duke Univ, Med Ctr, Durham, NC USA.
[Betts, Robert F.] Univ Rochester, New York, NY USA.
[Gelb, Larry D.] Vet Affairs Med Ctr, St Louis, MO USA.
[Pachucki, Constance T.] Hines Vet Affairs Med Ctr, Hines, IL USA.
[Keay, Susan K.] Vet Affairs Maryland Hlth Care Syst, Baltimore, MD USA.
[Keay, Susan K.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Menzies, Barbara; Neuzil, Kathy M.] Vet Affairs Med Ctr Puget Sound, Seattle, WA USA.
[Griffin, Marie R.] Vanderbilt Univ, Med Ctr, Nashville, TN USA.
[Kauffman, Carol A.] Vet Affairs Ann Arbor Healthcare Syst, Ann Arbor, MI USA.
[Kauffman, Carol A.] Univ Michigan, Sch Med, Ann Arbor, MI USA.
[Marques, Adriana R.] NIAID, Bethesda, MD 20892 USA.
[Toney, John F.] Vet Affairs Med Ctr, Tampa, FL USA.
[Simberkoff, Michael S.] VA New York Harbor Healthcare Syst, New York, NY USA.
[Simberkoff, Michael S.] NYU, Sch Med, New York, NY USA.
[Serrao, Richard; Arbeit, Robert D.] Boston Univ, Boston, MA 02215 USA.
[Gnann, John W.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA.
[Gnann, John W.] Univ Alabama Birmingham, Birmingham, AL USA.
[Greenberg, Richard N.] Univ Kentucky, Sch Med, Lexington, KY 40506 USA.
[Holodniy, Mark] Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA.
[Keitel, Wendy A.] Baylor Coll Med, Houston, TX 77030 USA.
[Yeh, Shingshing S.] Northport Vet Affairs Med Ctr, Northport, NY USA.
[Davis, Larry E.] Vet Affairs Med Ctr, Albuquerque, NM USA.
[Crawford, George E.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Johnson, Gary R.; Zhang, Jane H.] Dept Vet Affairs, Cooperat Studies Program, Coordinating Ctr, West Haven, CT USA.
[Chan, Ivan S. F.; Keller, Paul M.; Silber, Jeffrey L.; Annunziato, Paula W.] Merck Sharp & Dohme Corp, Whitehouse Stn, NJ USA.
[Boardman, Kathy D.] Dept Vet Affairs, Cooperat Studies Program, Clin Res Pharm Coordinating Ctr, Albuquerque, NM USA.
RP Morrison, VA (reprint author), VAMC, Hematol Oncol Sect, 111E,1 Vet Dr, Minneapolis, MN 55417 USA.
EM morri002@umn.edu
RI Irwin, Michael/H-4870-2013;
OI Irwin, Michael/0000-0002-1502-8431; Serrao, Richard/0000-0002-7440-8645
FU James R. and Jesse V. Scott Fund for Shingles Research
FX The study was conducted by the Cooperative Studies Program, Department
of Veterans Affairs, Office of Research and Development. Additional
support was provided by Merck Sharp & Dohme, by the James R. and Jesse
V. Scott Fund for Shingles Research, and by the Intramural Research
Program of the National Institute of Allergy and Infectious Diseases,
National Institutes of Health. Data management and analysis support was
provided at West Haven CSPCC by Karen Dellert and Kathy Newvine.
NR 9
TC 18
Z9 18
U1 0
U2 10
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD AUG 15
PY 2013
VL 208
IS 4
BP 559
EP 563
DI 10.1093/infdis/jit182
PG 5
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 191KO
UT WOS:000322412100005
PM 23633406
ER
PT J
AU Diaz, G
Melis, M
Tice, A
Kleiner, DE
Mishra, L
Zamboni, F
Farci, P
AF Diaz, Giacomo
Melis, Marta
Tice, Ashley
Kleiner, David E.
Mishra, Lopa
Zamboni, Fausto
Farci, Patrizia
TI Identification of microRNAs specifically expressed in hepatitis C
virus-associated hepatocellular carcinoma
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE liver; hepatocellular carcinoma; hepatitis C virus; microRNA;
pathogenesis
ID LIVER-DISEASE; CIRCULATING MICRORNAS; SUPPRESSOR GENE; CANCER;
OVEREXPRESSION; MIR-21; CONTRIBUTES; METASTASIS; PROGNOSIS; TARGET
AB Although several studies have investigated the association of miRNAs with hepatocellular carcinoma (HCC), the data published so far are not concordant. A reason for these discrepancies may be the fact that most studies used the nontumorous tissue surrounding the HCC lesion as a control, which is almost invariably affected by cirrhosis or chronic hepatitis, as well as other pathological conditions such as hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Moreover, HCC is often analyzed as a single group regardless of the different viral etiologies. The miRNAs differentially expressed in HCV-related HCC were investigated by comparing the tumorous tissues to a wide range of liver specimens, including healthy livers obtained from liver donors and patients who underwent liver resection for angioma, in addition to tissues from various acute and chronic liver diseases, including HCV-related cirrhosis not associated with HCC, HCV-related cirrhosis associated with HCC and HBV-associated acute liver failure. The whole set of 2,226 human miRNAs were examined, including 1,121 pre-miRNAs and 1,105 mature miRNAs, available in a microarray platform. Stringent statistical methods were applied to reduce the risk of false discoveries to less than 1%. These data identified 18 miRNAs exclusively expressed in HCV-associated HCC, characterized by high specificity and selectivity versus all other liver diseases and healthy conditions and connected into a regulatory network pivoting on p53, phosphatase and tensin homolog and all-trans retinoic acid signaling.
C1 [Diaz, Giacomo] Univ Cagliari, Dept Biomed Sci, Cagliari, Italy.
[Melis, Marta; Tice, Ashley; Farci, Patrizia] NIAID, Hepat Pathogenesis Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Kleiner, David E.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Mishra, Lopa] Univ Texas MD Anderson Canc Ctr, Dept Gastroenterol Hepatol & Nutr, Houston, TX 77030 USA.
[Zamboni, Fausto] Brotzu Hosp, Liver Transplantat Ctr, Cagliari, Italy.
RP Farci, P (reprint author), NIAID, Hepat Pathogenesis Sect, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM pfarci@niaid.nih.gov
OI Kleiner, David/0000-0003-3442-4453
FU Intramural Research Program of the National Institutes of Health;
National Institute of Allergy and Infectious Diseases; National Cancer
Institute; Fondazione Banco di Sardegna, Sassari, Italy [739/2011.1045]
FX Grant sponsors: Intramural Research Program of the National Institutes
of Health, National Institute of Allergy and Infectious Diseases,
National Cancer Institute; Grant sponsor: Fondazione Banco di Sardegna,
Sassari, Italy; Grant number: 739/2011.1045
NR 44
TC 23
Z9 23
U1 0
U2 30
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD AUG 15
PY 2013
VL 133
IS 4
BP 816
EP 824
DI 10.1002/ijc.28075
PG 9
WC Oncology
SC Oncology
GA 161LM
UT WOS:000320194400005
PM 23390000
ER
PT J
AU Hendrix, A
Sormunen, R
Westbroek, W
Lambein, K
Denys, H
Sys, G
Braems, G
Van den Broecke, R
Cocquyt, V
Gespach, C
Bracke, M
De Wever, O
AF Hendrix, An
Sormunen, Raija
Westbroek, Wendy
Lambein, Kathleen
Denys, Hannelore
Sys, Gwen
Braems, Geert
Van den Broecke, Rudy
Cocquyt, Veronique
Gespach, Christian
Bracke, Marc
De Wever, Olivier
TI Vacuolar H plus ATPase expression and activity is required for
Rab27B-dependent invasive growth and metastasis of breast cancer
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE proton pump; vesicle transport; exocytosis; Rab27; heat shock protein;
invasion
ID V-ATPASE; SUBUNIT; PROTEINS; ISOFORMS; PATHWAY
AB The secretory Rab27B small GTPase promotes invasive growth and metastasis in estrogen receptor (ER) -positive breast cancer cells by orchestrating the peripheral targeting of vesicles secreting proinvasive growth regulators. Increased Rab27B expression is associated with poor prognosis in breast cancer patients. The molecular mechanisms of peripheral Rab27B secretory vesicle distribution are poorly understood. Mass spectrometry analysis on green fluorescent protein (GFP)-Rab27B vesicles prepared from GFP-Rab27B transfected MCF-7 human breast cancer cells detected eight subunits of the vacuolar H(+)-ATPase (V-ATPase) and the presence of V0a1 and V0d1 subunits was confirmed by Western blot analysis. Reversible inhibition of V-ATPase activity by bafilomycin A1 or transient silencing of V0a1 or V0d1 subunits demonstrated that V-ATPase controls peripheral localization and size of Rab27B vesicles. V-ATPase expression and activity further controls Rab27B-induced collagen type I invasion, cell-cycle progression and invasive growth in the chorioallantoic membrane assay. In agreement, Rab27B-dependent extracellular heat shock protein90 release and matrix metalloprotease-2 activation is markedly reduced by bafilomycin A1 and transient silencing of V0a1 and V0d1 subunits. Poor prognosis ER-positive primary breast tumors expressing high levels of Rab27B also expressed multiple V-ATPase subunits and showed a strong cytoplasmic and peripheral V-ATPase V1E expression. In conclusion, inhibiting V-ATPase activity by interfering agents and drugs might be an effective strategy for blocking Rab27B-dependent proinvasive secretory vesicle trafficking in ER-positive breast cancer patients.
C1 [Hendrix, An; Bracke, Marc; De Wever, Olivier] Ghent Univ Hosp, Lab Expt Canc Res, Dept Radiat Oncol & Expt Canc Res, B-9000 Ghent, Belgium.
[Hendrix, An; Denys, Hannelore; Cocquyt, Veronique] Ghent Univ Hosp, Dept Med Oncol, B-9000 Ghent, Belgium.
[Sormunen, Raija] Univ Oulu, Dept Pathol, Electron Microscopy Lab, Bioctr Oulu, Oulu, Finland.
[Westbroek, Wendy] NHGRI, Med Genet Branch, Bethesda, MD 20892 USA.
[Lambein, Kathleen] Ghent Univ Hosp, Dept Pathol, B-9000 Ghent, Belgium.
[Sys, Gwen] Ghent Univ Hosp, Dept Orthoped Surg, B-9000 Ghent, Belgium.
[Braems, Geert; Van den Broecke, Rudy] Ghent Univ Hosp, Dept Gynecol, B-9000 Ghent, Belgium.
[Gespach, Christian] Hop St Antoine, INSERM, Mol & Clin Oncol U938, Fac Med, F-75571 Paris, France.
[Gespach, Christian] Univ Paris 06, F-75252 Paris 05, France.
RP Hendrix, A (reprint author), Ghent Univ Hosp, Lab Expt Canc Res, Dept Radiat Oncol & Expt Canc Res, De Pintelaan 185, B-9000 Ghent, Belgium.
EM an.hendrix@ugent.be
RI de wever, olivier/J-3094-2013
OI de wever, olivier/0000-0002-5453-760X
FU Fund for Scientific Spearheads of the Ghent University Hospital;
Stichting tegen Kanker; Intramural Research Program of the National
Human Genome Research Institute; Fund for Scientific Research-Flanders;
Research Council of Ghent University
FX Grant sponsors: Fund for Scientific Spearheads of the Ghent University
Hospital, Stichting tegen Kanker, The Intramural Research Program of the
National Human Genome Research Institute, Fund for Scientific
Research-Flanders, Research Council of Ghent University
NR 25
TC 26
Z9 27
U1 0
U2 37
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD AUG 15
PY 2013
VL 133
IS 4
BP 843
EP 854
DI 10.1002/ijc.28079
PG 12
WC Oncology
SC Oncology
GA 161LM
UT WOS:000320194400008
PM 23390068
ER
PT J
AU Sati, P
van Gelderen, P
Silva, AC
Reich, DS
Merkle, H
de Zwart, JA
Duyn, JH
AF Sati, Pascal
van Gelderen, Peter
Silva, Afonso C.
Reich, Daniel S.
Merkle, Hellmut
de Zwart, Jacco A.
Duyn, Jeff H.
TI Micro-compartment specific T*(2) relaxation in the brain
SO NEUROIMAGE
LA English
DT Article
DE Water compartment; T*(2) relaxation; Frequency shift; White matter;
Brain; Demyelination
ID HIGH-FIELD MRI; WHITE-MATTER CONTRAST; MYELIN WATER FRACTION; HUMAN
OCCIPITAL LOBE; GRADIENT-ECHO MRI; IN-VIVO; MAGNETIC-RESONANCE;
SUSCEPTIBILITY CONTRAST; FIBER ORIENTATION; MULTIPLE-SCLEROSIS
AB MRI at high field can be sensitized to the magnetic properties of tissues, which introduces a signal dependence on the orientation of white matter (WM) fiber bundles relative to the magnetic field. In addition, study of the NMR relaxation properties of this signal has indicated contributions from compartmentalized water environments inside and outside the myelin sheath that may be separable. Here we further investigated the effects of water compartmentalization on the MRI signal with the goal of extracting compartment-specific information. By comparing MRI measurements of human and marmoset brain at 7 T with magnetic field modeling, we show that: (1) water between the myelin lipid bilayers, in the axonal, and in the interstitial space each experience characteristic magnetic field effects that depend on fiber orientation (2) these field effects result in characteristic relaxation properties and frequency shifts for these compartments; and (3) compartmental contributions may be separated by multi-component fitting of the MRI signal relaxation (i.e. decay) curve. We further show the potential application of these findings to the direct mapping of myelin content and assessment of WM fiber integrity with high field MRI. Published by Elsevier Inc.
C1 [Sati, Pascal; Reich, Daniel S.] Natl Inst Neurol Disorders & Stroke, Translat Neuroradiol Unit, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA.
[van Gelderen, Peter; de Zwart, Jacco A.; Duyn, Jeff H.] Natl Inst Neurol Disorders & Stroke, Adv MRI Sect, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
[Silva, Afonso C.] Natl Inst Neurol Disorders & Stroke, Cerebral Microcirculat Unit, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
[Merkle, Hellmut] Natl Inst Neurol Disorders & Stroke, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
RP Duyn, JH (reprint author), Bldg 10,Room B1D724,10 Ctr Dr MSC 1400, Bethesda, MD 20892 USA.
EM jeff.duyn@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 (NINDS)
FX We thank Dr. Alan Koretsky for discussion. We also thank Xianfeng (Lisa)
Zhang for the animal preparation, and Susan C Guttman and the
Neuroimmunology Branch clinical group for coordinating the recruitment
of human subjects. We acknowledge the Intramural Research Program of the
National Institute of Neurological Disorders and Stroke (NINDS) for
support.
NR 62
TC 45
Z9 45
U1 0
U2 29
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD AUG 15
PY 2013
VL 77
BP 268
EP 278
DI 10.1016/j.neuroimage.2013.03.005
PG 11
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 159UX
UT WOS:000320073900027
PM 23528924
ER
PT J
AU Best, SM
AF Best, Sonja M.
TI Viruses Play Dead to TAMe Interferon Responses
SO CELL HOST & MICROBE
LA English
DT Editorial Material
ID RECEPTORS; SYSTEM; FAMILY
AB TAM receptors promote apoptotic cell uptake and function as inflammation suppressors. Many viruses mimic apoptotic cells, thus exploiting TAM receptors for attachment and entry. In this issue of Cell Host & Microbe, Bhattacharyya et al. show that TAM binding by enveloped viruses also induces receptor signaling to suppress cellular interferon responses.
C1 NIAID, NIH, Rocky Mt Labs, Virol Lab, Hamilton, MT 59840 USA.
RP Best, SM (reprint author), NIAID, NIH, Rocky Mt Labs, Virol Lab, Hamilton, MT 59840 USA.
EM sbest@niaid.nih.gov
FU Intramural NIH HHS [ZIA AI001125-01]
NR 10
TC 0
Z9 1
U1 0
U2 4
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 AUG 14
PY 2013
VL 14
IS 2
BP 117
EP 118
DI 10.1016/j.chom.2013.07.014
PG 2
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA AA1JE
UT WOS:000330851600001
PM 23954149
ER
PT J
AU Jacques, PF
Lyass, A
Massaro, JM
Vasan, RS
D'Agostino, RB
AF Jacques, Paul F.
Lyass, Asya
Massaro, Joseph M.
Vasan, Ramachandran S.
D'Agostino, Ralph B., Sr.
TI Relationship of lycopene intake and consumption of tomato products to
incident CVD
SO BRITISH JOURNAL OF NUTRITION
LA English
DT Article
DE Lycopene; CVD; CHD; Stroke
ID FOOD FREQUENCY QUESTIONNAIRE; CORONARY-HEART-DISEASE; PLASMA CAROTENOID
CONCENTRATIONS; CARDIOVASCULAR-DISEASE; VEGETABLE CONSUMPTION;
MYOCARDIAL-INFARCTION; DIETARY-INTAKE; RISK FACTOR; STROKE; COHORT
AB Evidence for cardioprotective effects of lycopene is inconsistent. Studies of circulating lycopene generally report inverse associations with CVD risk, but studies based on lycopene intake do not. The failure of dietary studies to support the findings based on biomarkers may be due in part to misclassification of lycopene intakes. To address this potential misclassification, we used repeated measures of intake obtained over 10 years to characterise the relationship between lycopene intake and the incidence of CVD (n 314), CHD (n 171) and stroke (n 99) in the Framingham Offspring Study. Hazard ratios (HR) for incident outcomes were derived from Cox proportional hazards regression models using logarithmically transformed lycopene intake adjusted for CVD risk factors and correlates of lycopene intake. HR were interpreted as the increased risk for a 2.7-fold difference in lycopene intake, a difference approximately equal to its interquartile range. Using an average of three intake measures with a 9-year follow-up, lycopene intake was inversely associated with CVD incidence (HR 0.83, 95% CI 0.70, 0.98). Using an average of two intake measures and 11 years of follow-up, lycopene intake was inversely associated with CHD incidence (HR 0.74, 95% CI 0.58, 0.94). Lycopene intake was unrelated to stroke incidence. The present study of lycopene intake and CVD provides supporting evidence for an inverse association between lycopene and CVD risk; however, additional research is needed to determine whether lycopene or other components of tomatoes, the major dietary source of lycopene, are responsible for the observed association.
C1 [Jacques, Paul F.] Tufts Univ, Jean Mayer US Dept Agr, Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
[Lyass, Asya; Vasan, Ramachandran S.; D'Agostino, Ralph B., Sr.] NHLBI Framingham Heart Study, Framingham, MA 01702 USA.
[Lyass, Asya; D'Agostino, Ralph B., Sr.] Boston Univ, Coll Arts & Sci, Dept Math & Stat, Boston, MA 02215 USA.
[Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
RP Jacques, PF (reprint author), Tufts Univ, Jean Mayer US Dept Agr, Human Nutr Res Ctr Aging, 711 Washington St, Boston, MA 02111 USA.
EM paul.jacques@tufts.edu
OI Massaro, Joseph/0000-0002-2682-4812; Ramachandran,
Vasan/0000-0001-7357-5970
FU European Union LYCOCARD Project through the Ministry of Education and
Cultural Affairs of the Free State of Thuringia, Germany [B514-09057];
National Institutes of Health/National Heart, Lung, and Blood Institute
[N01-HC-25,195]; United States Department of Agriculture [58-1950-7-707]
FX This study was supported by the European Union LYCOCARD Project through
grant no. B514-09057 from the Ministry of Education and Cultural Affairs
of the Free State of Thuringia, Germany, and by the National Institutes
of Health/National Heart, Lung, and Blood Institute (contract
N01-HC-25,195) and the United States Department of Agriculture
(agreement no. 58-1950-7-707). None of the authors has a conflict of
interest to declare. The authors' contributions were as follows: P. F.
J., R. S. V. and R. B. D'A. contributed to the study design; J. M. M.
provided the statistical guidance; A. L. performed the statistical
analyses; P. F. J. drafted the manuscript; P. F. J., R. S. V., R. B.
D'A., J. M. M. and A. L. contributed to the interpretation of the
results and the editing of the manuscript.
NR 43
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Z9 17
U1 4
U2 16
PU CAMBRIDGE UNIV PRESS
PI CAMBRIDGE
PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND
SN 0007-1145
J9 BRIT J NUTR
JI Br. J. Nutr.
PD AUG 14
PY 2013
VL 110
IS 3
BP 545
EP 551
DI 10.1017/S0007114512005417
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 189OO
UT WOS:000322276800019
PM 23317928
ER
PT J
AU MacIntosh, BA
Ramsden, CE
Faurot, KR
Zamora, D
Mangan, M
Hibbeln, JR
Mann, JD
AF MacIntosh, Beth A.
Ramsden, Christopher E.
Faurot, Keturah R.
Zamora, Daisy
Mangan, Margaret
Hibbeln, Joseph R.
Mann, J. Douglas
TI Low-n-6 and low-n-6 plus high-n-3 diets for use in clinical research
SO BRITISH JOURNAL OF NUTRITION
LA English
DT Article
DE n-6 Fatty acids; n-3 Fatty acids; Polyunsaturated fatty acids; Dietary
interventions; Headache
ID POLYUNSATURATED FATTY-ACIDS; DOUBLY LABELED WATER; ALPHA-LINOLENIC ACID;
HUMAN DEPOT FAT; ADIPOSE-TISSUE; MULTIPLE-PASS; ENERGY-INTAKE;
DOCOSAHEXAENOIC ACID; SUPPLEMENTATION; RECALL
AB Few trials have evaluated the metabolic effects and health outcomes of lowering dietary n-6 PUFA. The objectives of the present paper were (1) to report the methods employed to lower dietary n-6 PUFA, while either increasing or maintaining n-3 PUFA intake and (2) to validate our methods with 24 h recalls and erythrocyte fatty acid analyses. A total of sixty-seven subjects were randomised to either (1) an average-n-3 PUFA, low-n-6 PUFA (L6) intervention designed to lower linoleic acid (LA; <= 2.5% of energy (en%)) and arachidonic acid (<= 60 mg/d), while maintaining an average US intake of n-3 PUFA or (2) a high-n-3 PUFA, low-n-6 PUFA (H3-L6) intervention designed to lower n-6 LA, while increasing the n-3 PUFA alpha-linolenic acid (ALA; >= 1.5 en%) and EPA + DHA (>= 1000 mg/d). Pre- and intra-intervention nutrient intakes were estimated with six 24 h dietary recalls per subject. Both groups achieved the targeted reductions in dietary LA to <= 2.5 en% (median LA 2.45 (2.1, 3.1); P<0.001). Intakes of n-3 PUFA did not change for the L6 group. Target increases in n-3 ALA (median 1.6 en%, (1.3, 2.0), P<0.001) and EPA + DHA (1482 mg, (374, 2558), P<0.001) were achieved in the H3-L6 group. Dietary changes were validated by corresponding changes in erythrocyte n-6 and n-3 fatty acid composition. Dietary LA can be lowered to <= 2.5 en%, with or without concurrent increases in dietary n-3 PUFA, in an outpatient clinical trial setting using this integrated diet method.
C1 [MacIntosh, Beth A.] Univ N Carolina, North Carolina Translat Clin Sci Inst, Nutr Res & Metab Core, Chapel Hill, NC 27599 USA.
[Ramsden, Christopher E.; Hibbeln, Joseph R.] NIAAA, Sect Nutr Neurosci, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA.
[Faurot, Keturah R.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA.
[Faurot, Keturah R.; Zamora, Daisy] Univ N Carolina, Sch Med, Dept Phys Med & Rehabil, Program Integrat Med, Chapel Hill, NC 27599 USA.
[Mangan, Margaret] Univ N Carolina, Gillings Sch Publ Hlth, Nutr Obes Res Ctr Diet Phys Activ & Body Composit, Chapel Hill, NC 27599 USA.
[Mann, J. Douglas] Univ N Carolina, Sch Med, Dept Neurol, Chapel Hill, NC 27599 USA.
RP MacIntosh, BA (reprint author), Univ N Carolina, North Carolina Translat Clin Sci Inst, Nutr Res & Metab Core, 101 Manning Dr,CB 7600, Chapel Hill, NC 27599 USA.
EM beth_macintosh@med.unc.edu
FU Mayday Fund; North Carolina Clinical and Translational Sciences
Institute (NCRR, NIH) [UL1RR025747]; UNC Nutrition Obesity Research
Center, CHAI Core and Nutrition Epidemiology Core (NIDDK, NIH)
[DK056350]; UNC Research Fellowship in Complementary and Alternative
Medicine (NCCAM, NIH) [T32-AT003378]; Intramural Research Program of the
National Institute on Alcohol Abuse and Alcoholism, NIH
FX The authors declare that they have no competing interests. The authors
would like to thank the following individuals for their research
assistance: Marjorie Busby for expertise with study design; Gus Swenson
for study food production management; Dietetic Technicians Clarence
Mayo, Jim Howerton and Derrick Williams for preparation of study foods;
Olafur Palsson, Beth Fowler, Carol Carr, Regina McCoy and Tim McCaskill
(programmer) for design and functionality of the study website; Jim
Loewke for erythrocyte and nutrient composition analysis and Duk Hyun
for nutrient composition analyses; Chanee Lynch for study coordination;
and Rebecca Coble, Amit Ringel, Sharon Majchrzak-Hong and Joseph
Graciosa for general research assistance. B. A. M. was the lead
dietitian, developed the dietary intervention methods, provided
nutrition counselling to research subjects and contributed to the
initial draft and revisions of the manuscript. C. E. R. was the
co-principal investigator and contributed to the hypotheses, grant
application, study design and implementation and interpretation of the
initial draft and revisions of the manuscript. K. R. F. contributed to
the overall trial development and conduct, performed the statistical
analysis and revised the manuscript. D. Z. assisted with manuscript
preparation and statistical analysis. M. M. led the NORC research team
in creating custom user recipes, collecting the 24 h dietary recalls and
revised the manuscript. J. R. H. contributed to the study design and
interpretation and revised the manuscript. J. D. M. was the co-principal
investigator and the primary study clinician and contributed to all
aspects of the project. All authors contributed to the intellectual
content of the manuscript. The authors gratefully acknowledge funding
support for the present trial from the Mayday Fund (primary source); the
North Carolina Clinical and Translational Sciences Institute (grant
UL1RR025747, NCRR, NIH); the UNC Nutrition Obesity Research Center, CHAI
Core and Nutrition Epidemiology Core (grant DK056350, NIDDK, NIH); the
UNC Research Fellowship in Complementary and Alternative Medicine (grant
T32-AT003378, NCCAM, NIH); and the Intramural Research Program of the
National Institute on Alcohol Abuse and Alcoholism, NIH. Its contents
are solely the responsibility of the authors and do not necessarily
represent the official views of the Mayday Fund or the National
Institutes of Health.
NR 48
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U1 0
U2 12
PU CAMBRIDGE UNIV PRESS
PI CAMBRIDGE
PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND
SN 0007-1145
J9 BRIT J NUTR
JI Br. J. Nutr.
PD AUG 14
PY 2013
VL 110
IS 3
BP 559
EP 568
DI 10.1017/S0007114512005181
PG 10
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 189OO
UT WOS:000322276800021
PM 23328113
ER
PT J
AU Li, YY
Huang, WC
Niu, L
Umbach, DM
Covo, S
Li, LP
AF Li, Yuanyuan
Huang, Weichun
Niu, Liang
Umbach, David M.
Covo, Shay
Li, Leping
TI Characterization of constitutive CTCF/cohesin loci: a possible role in
establishing topological domains in mammalian genomes
SO BMC GENOMICS
LA English
DT Article
DE CTCF; Cohesin; Constitutive binding site; Chromatin interaction;
Topological domain
ID CCCTC-BINDING-FACTOR; C-MYC GENE; CTCF-BINDING; REGULATORY ELEMENTS;
DNA-REPLICATION; CHROMATIN INTERACTIONS; HYPERSENSITIVE SITES; COHESIN;
PROTEIN; ORGANIZATION
AB Background: Recent studies suggested that human/mammalian genomes are divided into large, discrete domains that are units of chromosome organization. CTCF, a CCCTC binding factor, has a diverse role in genome regulation including transcriptional regulation, chromosome-boundary insulation, DNA replication, and chromatin packaging. It remains unclear whether a subset of CTCF binding sites plays a functional role in establishing/maintaining chromatin topological domains.
Results: We systematically analysed the genomic, transcriptomic and epigenetic profiles of the CTCF binding sites in 56 human cell lines from ENCODE. We identified similar to 24,000 CTCF sites (referred to as constitutive sites) that were bound in more than 90% of the cell lines. Our analysis revealed: 1) constitutive CTCF loci were located in constitutive open chromatin and often co-localized with constitutive cohesin loci; 2) most constitutive CTCF loci were distant from transcription start sites and lacked CpG islands but were enriched with the full-spectrum CTCF motifs: a recently reported 33/34-mer and two other potentially novel (22/26-mer); 3) more importantly, most constitutive CTCF loci were present in CTCF-mediated chromatin interactions detected by ChIA-PET and these pair-wise interactions occurred predominantly within, but not between, topological domains identified by Hi-C.
Conclusions: Our results suggest that the constitutive CTCF sites may play a role in organizing/maintaining the recently identified topological domains that are common across most human cells.
C1 [Li, Yuanyuan; Huang, Weichun; Niu, Liang; Umbach, David M.; Li, Leping] Natl Inst Environm Hlth Sci, Biostat Branch, Durham, NC 27709 USA.
[Covo, Shay] Hebrew Univ Jerusalem, Robert H Smith Fac Agr Food & Environm, Dept Plant Pathol & Microbiol, Rehovot, Israel.
RP Li, LP (reprint author), Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, Durham, NC 27709 USA.
EM li3@niehs.nih.gov
FU Computational Biology Facility at NIEHS; Intramural Research Program of
the NIH, National Institute of Environmental Health Sciences [ES101765]
FX This research was supported by Intramural Research Program of the NIH,
National Institute of Environmental Health Sciences (ES101765).
NR 57
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U1 2
U2 22
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 AUG 14
PY 2013
VL 14
AR 553
DI 10.1186/1471-2164-14-553
PG 12
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 210NH
UT WOS:000323840000001
PM 23945083
ER
PT J
AU Bhullar, J
Natarajan, K
Shukla, S
Mathias, TJ
Sadowska, M
Ambudkar, SV
Baer, MR
AF Bhullar, Jasjeet
Natarajan, Karthika
Shukla, Suneet
Mathias, Trevor J.
Sadowska, Mariola
Ambudkar, Suresh V.
Baer, Maria R.
TI The FLT3 Inhibitor Quizartinib Inhibits ABCG2 at Pharmacologically
Relevant Concentrations, with Implications for Both Chemosensitization
and Adverse Drug Interactions
SO PLOS ONE
LA English
DT Article
ID ACUTE MYELOID-LEUKEMIA; CANCER RESISTANCE PROTEIN; HUMAN P-GLYCOPROTEIN;
TYROSINE KINASE INHIBITORS; ACUTE MYELOGENOUS LEUKEMIA;
MULTIDRUG-RESISTANCE; HEMATOPOIETIC-CELLS; TRANSPORTER ABCG2; CATALYTIC
CYCLE; ATP HYDROLYSIS
AB The oral second-generation bis-aryl urea fms-like tyrosine kinase 3 (FLT3) inhibitor quizartinib (AC220) has favorable kinase selectivity and pharmacokinetics. It inhibits mutant and wild-type FLT3 in vivo at 0.1 and 0.5 mu M, respectively, and has shown favorable activity and tolerability in phase I and II trials in acute myeloid leukemia, with QT prolongation as the dose-limiting toxicity. Co-administration with chemotherapy is planned. We characterized interactions of quizartinib with the ATP-binding cassette (ABC) proteins ABCB1 (P-glycoprotein) and ABCG2 (breast cancer resistance protein). Its effects on uptake of fluorescent substrates and apoptosis were measured by flow cytometry, binding to ABCB1 and ABCG2 drug-binding sites by effects on [I-125] iodoarylazidoprazosin ([I-125]-IAAP) photolabeling and ATPase activity, and cell viability by the WST-1 colorimetric assay. Quizartinib inhibited transport of fluorescent ABCG2 and ABCB1 substrates in ABCG2- and ABCB1-overexpressing cells in a concentration-dependent manner, from 0.1 to 5 mu M and from 0.5 to 10 mu M, respectively, and inhibited [I-125]-IAAP photolabeling of ABCG2 and ABCB1 with IC50 values of 0.07 and 3.3 mu M, respectively. Quizartinib at higher concentrations decreased ABCG2, but not ABCB1, ATPase activity. Co-incubation with quizartinib at 0.1 to 1 mu M sensitized ABCG2-overexpressing K562/ABCG2 and 8226/MR20 cells to ABCG2 substrate chemotherapy drugs in a concentration-dependent manner in cell viability and apoptosis assays. Additionally, quizartinib increased cellular uptake of the ABCG2 substrate fluoroquinolone antibiotic ciprofloxacin, which also prolongs the QT interval, in a concentration-dependent manner, predicting altered ciprofloxacin pharmacokinetics and pharmacodynamics when co-administered with quizartinib. Thus quizartinib inhibits ABCG2 at pharmacologically relevant concentrations, with implications for both chemosensitization and adverse drug interactions. These interactions should be considered in the design of treatment regimens combining quizartinib and chemotherapy drugs and in choice of concomitant medications to be administered with quizartinib.
C1 [Bhullar, Jasjeet; Natarajan, Karthika; Mathias, Trevor J.; Sadowska, Mariola; Baer, Maria R.] Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
[Shukla, Suneet; Ambudkar, Suresh V.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Baer, Maria R.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
RP Baer, MR (reprint author), Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
EM mbaer@umm.edu
OI Natarajan, Karthika/0000-0001-7435-1477
FU Leukemia and Lymphoma Society Translational Research Award; University
of Maryland, Baltimore UMMG Cancer Research Grant [CH 649 CRF]; State of
Maryland Department of Health and Mental Hygiene (DHMH) under the
Cigarette Restitution Fund Program; NCI Cancer Center Support Grant [P30
CA134274]; NIH, National Cancer Institute, Center for Cancer Research
FX Leukemia and Lymphoma Society Translational Research Award (MRB),
University of Maryland, Baltimore UMMG Cancer Research Grant #CH 649 CRF
issued by the State of Maryland Department of Health and Mental Hygiene
(DHMH) under the Cigarette Restitution Fund Program, NCI Cancer Center
Support Grant P30 CA134274, and the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research (SS, SVA).
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 69
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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 AUG 14
PY 2013
VL 8
IS 8
AR e71266
DI 10.1371/journal.pone.0071266
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 202MQ
UT WOS:000323221500065
PM 23967177
ER
PT J
AU Funk, S
Bogich, TL
Jones, KE
Kilpatrick, AM
Daszak, P
AF Funk, Sebastian
Bogich, Tiffany L.
Jones, Kate E.
Kilpatrick, A. Marm
Daszak, Peter
TI Quantifying Trends in Disease Impact to Produce a Consistent and
Reproducible Definition of an Emerging Infectious Disease
SO PLOS ONE
LA English
DT Article
ID EMERGENCE; HEALTH; EPIDEMIOLOGY; PERSPECTIVE; REGRESSION; PATHOGENS;
EVOLUTION; ECOLOGY
AB The proper allocation of public health resources for research and control requires quantification of both a disease's current burden and the trend in its impact. Infectious diseases that have been labeled as "emerging infectious diseases'' (EIDs) have received heightened scientific and public attention and resources. However, the label 'emerging' is rarely backed by quantitative analysis and is often used subjectively. This can lead to over-allocation of resources to diseases that are incorrectly labelled "emerging,'' and insufficient allocation of resources to diseases for which evidence of an increasing or high sustained impact is strong. We suggest a simple quantitative approach, segmented regression, to characterize the trends and emergence of diseases. Segmented regression identifies one or more trends in a time series and determines the most statistically parsimonious split(s) (or joinpoints) in the time series. These joinpoints in the time series indicate time points when a change in trend occurred and may identify periods in which drivers of disease impact change. We illustrate the method by analyzing temporal patterns in incidence data for twelve diseases. This approach provides a way to classify a disease as currently emerging, re-emerging, receding, or stable based on temporal trends, as well as to pinpoint the time when the change in these trends happened. We argue that quantitative approaches to defining emergence based on the trend in impact of a disease can, with appropriate context, be used to prioritize resources for research and control. Implementing this more rigorous definition of an EID will require buy-in and enforcement from scientists, policy makers, peer reviewers and journal editors, but has the potential to improve resource allocation for global health.
C1 [Funk, Sebastian; Jones, Kate E.] Zool Soc London, Inst Zool, London NW1 4RY, England.
[Funk, Sebastian; Bogich, Tiffany L.] Princeton Univ, Dept Ecol & Evolut Biol, Princeton, NJ 08544 USA.
[Funk, Sebastian] London Sch Hyg & Trop Med, London WC1, England.
[Bogich, Tiffany L.; Daszak, Peter] EcoHlth Alliance, New York, NY USA.
[Bogich, Tiffany L.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Jones, Kate E.] UCL, Dept Genet Evolut & Environm, London, England.
[Kilpatrick, A. Marm] Univ Calif Santa Cruz, Dept Ecol & Evolutionary Biol, Santa Cruz, CA 95064 USA.
RP Kilpatrick, AM (reprint author), Univ Calif Santa Cruz, Dept Ecol & Evolutionary Biol, Santa Cruz, CA 95064 USA.
EM akilpatr@ucsc.edu; daszak@ecohealthalliance.org
RI Jones, Kate/G-4768-2010;
OI Jones, Kate/0000-0001-5231-3293; Bogich, Tiffany/0000-0002-8143-5289;
Funk, Sebastian/0000-0002-2842-3406
FU Fogarty International Center [2R01-TW005869]; NSF [EF-0914866, DEB
-1115895]; National Institute of Health [1R01AI090159]; National Science
Foundation Human and Social Dynamics 'Agents of Change' award
[BCS-0826779]
FX This work was made possible by the generous support of the American
people through the United States Agency for International Development
(USAID) Emerging Pandemic Threats PREDICT; by three NIH/NSF "Ecology and
Evolution of Infectious Diseases'' awards from the Fogarty International
Center (2R01-TW005869) and NSF (EF-0914866 and DEB -1115895), a grant
from the National Institute of Health (1R01AI090159), and by a National
Science Foundation Human and Social Dynamics 'Agents of Change' award
(BCS-0826779). TLB acknowledges the Research and Policy for Infectious
Disease Dynamics (RAPIDD) program of the Science and Technology
Directorate, U. S. Department of Homeland Security, and the Fogarty
International Center, NIH. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 34
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Z9 4
U1 7
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 AUG 14
PY 2013
VL 8
IS 8
AR e69951
DI 10.1371/journal.pone.0069951
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 202MQ
UT WOS:000323221500010
PM 23967065
ER
PT J
AU Konstandi, M
Shah, YM
Matsubara, T
Gonzalez, FJ
AF Konstandi, Maria
Shah, Yatrik M.
Matsubara, Tsutomu
Gonzalez, Frank J.
TI Role of PPAR alpha and HNF4 alpha in Stress-Mediated Alterations in
Lipid Homeostasis
SO PLOS ONE
LA English
DT Article
ID PROLIFERATOR-ACTIVATED RECEPTORS; PSYCHOLOGICAL STRESS; METABOLIC
SYNDROME; TARGETED DISRUPTION; OBESITY; CATECHOLAMINES; TRIGLYCERIDE;
CHOLESTEROL; SECRETION; GENE
AB Stress is a risk factor for several cardiovascular pathologies. PPAR alpha holds a fundamental role in control of lipid homeostasis by directly regulating genes involved in fatty acid transport and oxidation. Importantly, PPAR alpha agonists are effective in raising HDL-cholesterol and lowering triglycerides, properties that reduce the risk for cardiovascular diseases. This study investigated the role of stress and adrenergic receptor (AR)-related pathways in PPAR alpha and HNF4 alpha regulation and signaling in mice following repeated restraint stress or treatment with AR-antagonists administered prior to stress to block AR-linked pathways. Repeated restraint stress up-regulated Ppar alpha and its target genes in the liver, including Acox, Acot1, Acot4, Cyp4a10, Cyp4a14 and Lipin2, an effect that was highly correlated with Hnf4 alpha. In vitro studies using primary hepatocyte cultures treated with epinephrine or AR-agonists confirmed that hepatic AR/cAMP/PKA/CREB- and JNK-linked pathways are involved in PPAR alpha and HNF4 alpha regulation. Notably, restraint stress, independent of PPAR alpha, suppressed plasma triglyceride levels. This stress-induced effect could be attributed in part to hormone sensitive lipase activation in the white adipose tissue, which was not prevented by the increased levels of perilipin. Overall, this study identifies a mechanistic basis for the modification of lipid homeostasis following stress and potentially indicates novel roles for PPAR alpha and HNF4 alpha in stress-induced lipid metabolism.
C1 [Konstandi, Maria; Shah, Yatrik M.; Matsubara, Tsutomu; Gonzalez, Frank J.] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA.
[Konstandi, Maria] Univ Ioannina, Sch Med, Dept Pharmacol, GR-45110 Ioannina, Greece.
[Shah, Yatrik M.] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA.
RP Konstandi, M (reprint author), NCI, Lab Metab, NIH, Bethesda, MD 20892 USA.
EM mkonstan@cc.uoi.gr
FU National Cancer Institute Intramural Research Program; Molecular Life
Science, University of Oslo; Norwegian Cancer Society [PR-2006-0442,
PR-2007-0166]
FX This study was supported by the National Cancer Institute Intramural
Research Program. ML is supported as a PhD student by Molecular Life
Science, University of Oslo and the study is supported by the Norwegian
Cancer Society (PR-2006-0442, RAL; PR-2007-0166, RIS). The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 71
TC 5
Z9 6
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 AUG 14
PY 2013
VL 8
IS 8
AR e70675
DI 10.1371/journal.pone.0070675
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 202MQ
UT WOS:000323221500023
PM 23967086
ER
PT J
AU Munro, TA
Huang, XP
Inglese, C
Perrone, MG
Van't Veer, A
Carroll, FI
Beguin, C
Carlezon, WA
Colabufo, NA
Cohen, BM
Roth, BL
AF Munro, Thomas A.
Huang, Xi-Ping
Inglese, Carmela
Perrone, Maria Grazia
Van't Veer, Ashlee
Carroll, F. Ivy
Beguin, Cecile
Carlezon, William A., Jr.
Colabufo, Nicola A.
Cohen, Bruce M.
Roth, Bryan L.
TI Selective kappa Opioid Antagonists nor-BNI, GNTI and JDTic Have Low
Affinities for Non-Opioid Receptors and Transporters
SO PLOS ONE
LA English
DT Article
ID NOCICEPTIN/ORPHANIN FQ RECEPTOR; ALLOSTERIC MODULATION; P-GLYCOPROTEIN;
SPINAL-CORD; IN-VITRO; MICE; LIGANDS; SITE; BINALTORPHIMINE; AGONISTS
AB Background: Nor-BNI, GNTI and JDTic induce selective kappa opioid antagonism that is delayed and extremely prolonged, but some other effects are of rapid onset and brief duration. The transient effects of these compounds differ, suggesting that some of them may be mediated by other targets.
Results: In binding assays, the three antagonists showed no detectable affinity (K-i >= 10 mu M) for most non-opioid receptors and transporters (26 of 43 tested). There was no non-opioid target for which all three compounds shared detectable affinity, or for which any two shared sub-micromolar affinity. All three compounds showed low nanomolar affinity for kappa opioid receptors, with moderate selectivity over mu and delta (3 to 44-fold). Nor-BNI bound weakly to the alpha(2C)-adrenoceptor (K-i = 630 nM). GNTI enhanced calcium mobilization by noradrenaline at the alpha(1A)-adrenoceptor (EC50 = 41 nM), but did not activate the receptor, displace radioligands, or enhance PI hydrolysis. This suggests that it is a functionally-selective allosteric enhancer. GNTI was also a weak M-1 receptor antagonist (K-B = 3.7 mu M). JDTic bound to the noradrenaline transporter (K-i = 54 nM), but only weakly inhibited transport (IC50 = 1.1 mu M). JDTic also bound to the opioid-like receptor NOP (K-i = 12 nM), but gave little antagonism even at 30 mu M. All three compounds exhibited rapid permeation and active efflux across Caco-2 cell monolayers.
Conclusions: Across 43 non-opioid CNS targets, only GNTI exhibited a potent functional effect (allosteric enhancement of alpha(1A)-adrenoceptors). This may contribute to GNTI's severe transient effects. Plasma concentrations of nor-BNI and GNTI may be high enough to affect some peripheral non-opioid targets. Nonetheless, kappa opioid antagonism persists for weeks or months after these transient effects dissipate. With an adequate pre-administration interval, our results therefore strengthen the evidence that nor-BNI, GNTI and JDTic are highly selective kappa opioid antagonists.
C1 [Munro, Thomas A.; Van't Veer, Ashlee; Beguin, Cecile; Carlezon, William A., Jr.; Cohen, Bruce M.] McLean Hosp, Belmont, MA 02178 USA.
[Munro, Thomas A.; Van't Veer, Ashlee; Beguin, Cecile; Carlezon, William A., Jr.; Cohen, Bruce M.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Munro, Thomas A.] Univ Melbourne, Sch Chem, Parkville, Vic 3052, Australia.
[Munro, Thomas A.] Univ Melbourne, Inst Bio21, Parkville, Vic 3052, Australia.
[Huang, Xi-Ping; Roth, Bryan L.] Univ N Carolina, Sch Med, Natl Inst Mental Hlth Psychoact Drug Screening Pr, Chapel Hill, NC USA.
[Huang, Xi-Ping; Roth, Bryan L.] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC USA.
[Inglese, Carmela; Perrone, Maria Grazia; Colabufo, Nicola A.] Univ Bari, Dipartimento Farm Sci Farmaco, Bari, Italy.
[Carroll, F. Ivy] Res Triangle Inst, Ctr Organ & Med Chem, Res Triangle Pk, NC 27709 USA.
RP Munro, TA (reprint author), McLean Hosp, 115 Mill St, Belmont, MA 02178 USA.
EM thomas@munro.com
RI Munro, Thomas/B-2712-2009; Roth, Bryan/F-3928-2010;
OI Munro, Thomas/0000-0002-3366-7149; Perrone, Maria
Grazia/0000-0003-4195-5228
FU National Institute of Mental Health; National Institute of Drug Abuse
[DA09045, DA030586]; Department of Defense (National Defense Science and
Engineering Graduate Fellowship); Ministero dell'Istruzione,
dell'Universita e della Ricerca, Italy (MIUR) [PRIN 20097FJHPZ-001]
FX Funding was provided by: the National Institute of Mental Health
(Psychoactive Drug Screening Program, administered by BLR); National
Institute of Drug Abuse (DA09045 to FIC and DA030586 to WAC); Department
of Defense (National Defense Science and Engineering Graduate Fellowship
to AVV); and Ministero dell'Istruzione, dell'Universita e della Ricerca,
Italy (MIUR, PRIN 20097FJHPZ-001 to NAC). The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 60
TC 6
Z9 6
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 AUG 14
PY 2013
VL 8
IS 8
AR e70701
DI 10.1371/journal.pone.0070701
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 202MQ
UT WOS:000323221500024
PM 23976952
ER
PT J
AU Ono, M
Inkson, CA
Sonn, R
Kilts, TM
de Castro, LF
Maeda, A
Fisher, LW
Robey, PG
Berendsen, AD
Li, L
McCartney-Francis, N
Brown, AC
Crawford, NPS
Molinolo, A
Jain, A
Fedarko, NS
Young, MF
AF Ono, Mitsuaki
Inkson, Colette A.
Sonn, Robert
Kilts, Tina M.
de Castro, Luis F.
Maeda, Azusa
Fisher, Larry W.
Robey, Pamela G.
Berendsen, Agnes D.
Li, Li
McCartney-Francis, Nancy
Brown, Aaron C.
Crawford, Nigel P. S.
Molinolo, Alfredo
Jain, Alka
Fedarko, Neal S.
Young, Marian F.
TI WISP1/CCN4: A Potential Target for Inhibiting Prostate Cancer Growth and
Spread to Bone
SO PLOS ONE
LA English
DT Article
ID HUMAN CHONDROSARCOMA CELLS; PANCREATIC TUMOR-GROWTH; IN-VIVO;
DIFFERENTIAL EXPRESSION; FACTOR CTGF/CCN2; BREAST-CANCER; METASTASIS;
WISP-1; CYR61; MECHANISMS
AB Prostate cancer (PC) is a leading cause of death in men however the factors that regulate its progression and eventual metastasis to bone remain unclear. Here we show that WISP1/CCN4 expression in prostate cancer tissues was up-regulated in early stages of the disease and, further, that it correlated with increased circulating levels of WISP1 in the sera of patients at early stages of the disease. WISP1 was also elevated in the mouse prostate cancer model TRAMP in the hypoplastic diseased tissue that develops prior to advanced carcinoma formation. When the ability of anti-WISP1 antibodies to reduce the spread of PC3-Luc cells to distant sites was tested it showed that twice weekly injections of anti-WISP1 antibodies reduced the number and overall size of distant tumors developed after intracardiac (IC) injection of PC3-Luc cells in mice. The ability of antibodies against WISP1 to inhibit growth of PC3-Luc cancer cells in mice was also evaluated and showed that twice weekly injections of anti-WISP1 antibodies reduced local tumor growth when examined in xenografts. To better understand the mechanism of action, the migration of PC3-Luc cells through membranes with or without a Matrigel (TM) barrier showed the cells were attracted to WISP1, and that this attraction was inhibited by treatment with anti-WISP1 antibodies. We also show the expression of WISP1 at the bone-tumor interface and in the stroma of early grade cancers suggested WISP1 expression is well placed to play roles in both fostering growth of the cancer and its spread to bone. In summary, the up-regulation of WISP1 in the early stages of cancer development coupled with its ability to inhibit spread and growth of prostate cancer cells makes it both a potential target and an accessible diagnostic marker for prostate cancer.
C1 [Ono, Mitsuaki; Inkson, Colette A.; Sonn, Robert; Kilts, Tina M.; de Castro, Luis F.; Maeda, Azusa; Fisher, Larry W.; Robey, Pamela G.; Berendsen, Agnes D.; Li, Li; McCartney-Francis, Nancy; Brown, Aaron C.; Young, Marian F.] NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA.
[Molinolo, Alfredo] NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA.
[Crawford, Nigel P. S.] NHGRI, Metastasis Genet Sect, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
[Jain, Alka; Fedarko, Neal S.] Johns Hopkins Sch Med, Div Geriatr Med & Gerontol, Baltimore, MD USA.
[Ono, Mitsuaki] Okayama Univ, Dept Oral Rehabil & Regenerat Med, Grad Sch Med Dent & Pharmaceut Sci, Okayama 7008530, Japan.
[Inkson, Colette A.] Univ Manchester, Fac Life Sci, Manchester Immunol Grp, Manchester, Lancs, England.
RP Young, MF (reprint author), NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA.
EM myoung@dir.nicdr.nih.gov
RI Robey, Pamela/H-1429-2011;
OI Robey, Pamela/0000-0002-5316-5576; Fedarko, Neal/0000-0001-6055-6279;
Inkson, Colette/0000-0003-1215-312X
FU Division of Intramural Research, NIDCR of the Intramural Research
Program, NIH, DHHS; Department of Defense [W81XWH-11-1-0239]; Howard
Hughes Scholarship
FX This research was supported by the Division of Intramural Research,
NIDCR of the Intramural Research Program, NIH, DHHS (MO, CAI, TMK, LFCD,
AM (Maeda), LWF, PGR, ADB, LL NM-F, ACB, NPSC, AM (Molinolo) and MFY),
by a grant from the Department of Defense W81XWH-11-1-0239 (AJ and NSF)
and by a Howard Hughes Scholarship (RS). The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 48
TC 24
Z9 25
U1 0
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 14
PY 2013
VL 8
IS 8
AR e71709
DI 10.1371/journal.pone.0071709
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 202MQ
UT WOS:000323221500098
PM 23977121
ER
PT J
AU Chow, MZ
Boheler, KR
Li, RA
AF Chow, Maggie Zi
Boheler, Kenneth R.
Li, Ronald A.
TI Human pluripotent stem cell-derived cardiomyocytes for heart
regeneration, drug discovery and disease modeling: from the genetic,
epigenetic, and tissue modeling perspectives
SO STEM CELL RESEARCH & THERAPY
LA English
DT Review
DE Human embryonic stem cell; Induced pluripotent stem cell; Cardiomyocyte;
Epigenetic regulations; Chromatin remodeling; Histone modification;
Regenerative medicine; Cardiac differentiation
ID HUMAN PERIPHERAL-BLOOD; LONG-QT SYNDROME; CARDIOVASCULAR PROGENITORS;
CARDIAC DIFFERENTIATION; HUMAN FIBROBLASTS; DEFINED FACTORS; VENTRICULAR
CARDIOMYOCYTES; FACILITATED MATURATION; MYOCARDIAL-INFARCTION; RAT
HEARTS
AB Heart diseases remain a major cause of mortality and morbidity worldwide. However, terminally differentiated human adult cardiomyocytes (CMs) possess a very limited innate ability to regenerate. Directed differentiation of human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) into CMs has enabled clinicians and researchers to pursue the novel therapeutic paradigm of cell-based cardiac regeneration. In addition to tissue engineering and transplantation studies, the need for functional CMs has also prompted researchers to explore molecular pathways and develop strategies to improve the quality, purity and quantity of hESC-derived and iPSC-derived CMs. In this review, we describe various approaches in directed CM differentiation and driven maturation, and discuss potential limitations associated with hESCs and iPSCs, with an emphasis on the role of epigenetic regulation and chromatin remodeling, in the context of the potential and challenges of using hESC-CMs and iPSC-CMs for drug discovery and toxicity screening, disease modeling, and clinical applications.
C1 [Chow, Maggie Zi; Boheler, Kenneth R.; Li, Ronald A.] Univ Hong Kong, Fac Med, Stem Cell & Regenerat Med Consortium, Hong Kong, Hong Kong, Peoples R China.
[Chow, Maggie Zi; Boheler, Kenneth R.; Li, Ronald A.] Univ Hong Kong, Dept Physiol, Hong Kong, Hong Kong, Peoples R China.
[Boheler, Kenneth R.] NIA, Mol Cardiol & Stem Cell Unit, Cardiovasc Sci Lab, NIH,Gerontol Res Ctr, Baltimore, MD 21224 USA.
[Li, Ronald A.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA.
RP Li, RA (reprint author), Univ Hong Kong, Fac Med, Stem Cell & Regenerat Med Consortium, 5 Sassoon Rd,Hong Kong Jockey Club Bldg Interdisc, Hong Kong, Hong Kong, Peoples R China.
EM ronaldli@hkucc.hku.hk
NR 119
TC 10
Z9 11
U1 1
U2 44
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1757-6512
J9 STEM CELL RES THER
JI Stem Cell Res. Ther.
PD AUG 14
PY 2013
VL 4
AR 97
DI 10.1186/1757-6512-4-97
PG 13
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 201XA
UT WOS:000323175100003
PM 23953772
ER
PT J
AU Murray, CJL
Abraham, J
Ali, MK
Alvarado, M
Atkinson, C
Baddour, LM
Bartels, DH
Benjamin, EJ
Bhalla, K
Birbeck, G
Bolliger, I
Burstein, R
Carnahan, E
Chen, HL
Chou, D
Chugh, SS
Cohen, A
Colson, KE
Cooper, LT
Couser, W
Criqui, MH
Dabhadkar, KC
Dahodwala, N
Danaei, G
Dellavalle, RP
Des Jarlais, DC
Dicker, D
Ding, EL
Dorsey, R
Duber, H
Ebel, BE
Engell, RE
Ezzati, M
Felson, DT
Finucane, MM
Flaxman, S
Flaxman, AD
Fleming, T
Forouzanfar, MH
Freedman, G
Freeman, MK
Gabriel, SE
Gakidou, E
Gillum, RF
Gonzalez-Medina, D
Gosselin, R
Grant, B
Gutierrez, HR
Hagan, H
Havmoeller, R
Hoffman, H
Jacobsen, KH
James, SL
Jasrasaria, R
Jayaraman, S
Johns, N
Kassebaum, N
Khatibzadeh, S
Knowlton, LM
Lan, Q
Leasher, JL
Lim, S
Lin, JK
Lipshultz, SE
London, S
Lozano, R
Lu, Y
MacIntyre, MF
Mallinger, L
McDermott, MM
Meltzer, M
Mensah, GA
Michaud, C
Miller, TR
Mock, C
Moffitt, TE
Mokdad, AA
Mokdad, AH
Moran, AE
Mozaffarian, D
Murphy, T
Naghavi, M
Narayan, KMV
Nelson, RG
Olives, C
Omer, SB
Ortblad, K
Ostro, B
Pelizzari, PM
Phillips, D
Pope, CA
Raju, M
Ranganathan, D
Razavi, H
Ritz, B
Rivara, FP
Roberts, T
Sacco, RL
Salomon, JA
Sampson, U
Sanman, E
Sapkota, A
Schwebel, DC
Shahraz, S
Shibuya, K
Shivakoti, R
Silberberg, D
Singh, GM
Singh, D
Singh, JA
Sleet, DA
Steenland, K
Tavakkoli, M
Taylor, JA
Thurston, GD
Towbin, JA
Vavilala, MS
Vos, T
Wagner, GR
Weinstock, MA
Weisskopf, MG
Wilkinson, JD
Wulf, S
Zabetian, A
Lopez, AD
AF Murray, Christopher J. L.
Abraham, Jerry
Ali, Mohammed K.
Alvarado, Miriam
Atkinson, Charles
Baddour, Larry M.
Bartels, David H.
Benjamin, Emelia J.
Bhalla, Kavi
Birbeck, Gretchen
Bolliger, Ian
Burstein, Roy
Carnahan, Emily
Chen, Honglei
Chou, David
Chugh, Sumeet S.
Cohen, Aaron
Colson, K. Ellicott
Cooper, Leslie T.
Couser, William
Criqui, Michael H.
Dabhadkar, Kaustubh C.
Dahodwala, Nabila
Danaei, Goodarz
Dellavalle, Robert P.
Des Jarlais, Don C.
Dicker, Daniel
Ding, Eric L.
Dorsey, Ray
Duber, Herbert
Ebel, Beth E.
Engell, Rebecca E.
Ezzati, Majid
Felson, David T.
Finucane, Mariel M.
Flaxman, Seth
Flaxman, Abraham D.
Fleming, Thomas
Forouzanfar, Mohammad H.
Freedman, Greg
Freeman, Michael K.
Gabriel, Sherine E.
Gakidou, Emmanuela
Gillum, Richard F.
Gonzalez-Medina, Diego
Gosselin, Richard
Grant, Bridget
Gutierrez, Hialy R.
Hagan, Holly
Havmoeller, Rasmus
Hoffman, Howard
Jacobsen, Kathryn H.
James, Spencer L.
Jasrasaria, Rashmi
Jayaraman, Sudha
Johns, Nicole
Kassebaum, Nicholas
Khatibzadeh, Shahab
Knowlton, Lisa Marie
Lan, Qing
Leasher, Janet L.
Lim, Stephen
Lin, John Kent
Lipshultz, Steven E.
London, Stephanie
Lozano, Rafael
Lu, Yuan
MacIntyre, Michael F.
Mallinger, Leslie
McDermott, Mary M.
Meltzer, Michele
Mensah, George A.
Michaud, Catherine
Miller, Ted R.
Mock, Charles
Moffitt, Terrie E.
Mokdad, Ali A.
Mokdad, Ali H.
Moran, Andrew E.
Mozaffarian, Dariush
Murphy, Tasha
Naghavi, Mohsen
Narayan, K. M. Venkat
Nelson, Robert G.
Olives, Casey
Omer, Saad B.
Ortblad, Katrina
Ostro, Bart
Pelizzari, Pamela M.
Phillips, David
Pope, C. Arden, III
Raju, Murugesan
Ranganathan, Dharani
Razavi, Homie
Ritz, Beate
Rivara, Frederick P.
Roberts, Thomas
Sacco, Ralph L.
Salomon, Joshua A.
Sampson, Uchechukwu
Sanman, Ella
Sapkota, Amir
Schwebel, David C.
Shahraz, Saeid
Shibuya, Kenji
Shivakoti, Rupak
Silberberg, Donald
Singh, Gitanjali M.
Singh, David
Singh, Jasvinder A.
Sleet, David A.
Steenland, Kyle
Tavakkoli, Mohammad
Taylor, Jennifer A.
Thurston, George D.
Towbin, Jeffrey A.
Vavilala, Monica S.
Vos, Theo
Wagner, Gregory R.
Weinstock, Martin A.
Weisskopf, Marc G.
Wilkinson, James D.
Wulf, Sarah
Zabetian, Azadeh
Lopez, Alan D.
CA Us Burden Dis Collaborators
TI The State of US Health, 1990-2010 Burden of Diseases, Injuries, and Risk
Factors
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID BODY-MASS INDEX; ADJUSTED LIFE YEARS; GLOBAL BURDEN; SYSTEMATIC
ANALYSIS; UNITED-STATES; PUBLIC-HEALTH; CARDIOVASCULAR-DISEASE; BUILT
ENVIRONMENT; PHYSICAL-ACTIVITY; BLOOD-PRESSURE
AB IMPORTANCE Understanding the major health problems in the United States and how they are changing over time is critical for informing national health policy.
OBJECTIVES To measure the burden of diseases, injuries, and leading risk factors in the United States from 1990 to 2010 and to compare these measurements with those of the 34 countries in the Organisation for Economic Co-operation and Development (OECD) countries.
DESIGN We used the systematic analysis of descriptive epidemiology of 291 diseases and injuries, 1160 sequelae of these diseases and injuries, and 67 risk factors or clusters of risk factors from 1990 to 2010 for 187 countries developed for the Global Burden of Disease 2010 Study to describe the health status of the United States and to compare US health outcomes with those of 34 OECD countries. Years of life lost due to premature mortality (YLLs) were computed by multiplying the number of deaths at each age by a reference life expectancy at that age. Years lived with disability (YLDs) were calculated by multiplying prevalence (based on systematic reviews) by the disability weight (based on population-based surveys) for each sequela; disability in this study refers to any short- or long-term loss of health. Disability-adjusted life-years (DALYs) were estimated as the sum of YLDs and YLLs. Deaths and DALYs related to risk factors were based on systematic reviews and meta-analyses of exposure data and relative risks for risk-outcome pairs. Healthy life expectancy (HALE) was used to summarize overall population health, accounting for both length of life and levels of ill health experienced at different ages.
RESULTS US life expectancy for both sexes combined increased from 75.2 years in 1990 to 78.2 years in 2010; during the same period, HALE increased from 65.8 years to 68.1 years. The diseases and injuries with the largest number of YLLs in 2010 were ischemic heart disease, lung cancer, stroke, chronic obstructive pulmonary disease, and road injury. Age-standardized YLL rates increased for Alzheimer disease, drug use disorders, chronic kidney disease, kidney cancer, and falls. The diseases with the largest number of YLDs in 2010 were low back pain, major depressive disorder, other musculoskeletal disorders, neck pain, and anxiety disorders. As the US population has aged, YLDs have comprised a larger share of DALYs than have YLLs. The leading risk factors related to DALYs were dietary risks, tobacco smoking, high body mass index, high blood pressure, high fasting plasma glucose, physical inactivity, and alcohol use. Among 34 OECD countries between 1990 and 2010, the US rank for the age-standardized death rate changed from 18th to 27th, for the age-standardized YLL rate from 23rd to 28th, for the age-standardized YLD rate from 5th to 6th, for life expectancy at birth from 20th to 27th, and for HALE from 14th to 26th.
CONCLUSIONS AND RELEVANCE From 1990 to 2010, the United States made substantial progress in improving health. Life expectancy at birth and HALE increased, all-cause death rates at all ages decreased, and age-specific rates of years lived with disability remained stable. However, morbidity and chronic disability now account for nearly half of the US health burden, and improvements in population health in the United States have not kept pace with advances in population health in other wealthy nations.
C1 [Murray, Christopher J. L.; Alvarado, Miriam; Atkinson, Charles; Bolliger, Ian; Burstein, Roy; Carnahan, Emily; Chou, David; Colson, K. Ellicott; Dicker, Daniel; Duber, Herbert; Engell, Rebecca E.; Flaxman, Abraham D.; Gakidou, Emmanuela; Gonzalez-Medina, Diego; James, Spencer L.; Jasrasaria, Rashmi; Johns, Nicole; Lim, Stephen; MacIntyre, Michael F.; Mallinger, Leslie; Mokdad, Ali A.; Mokdad, Ali H.; Murphy, Tasha; Naghavi, Mohsen; Ortblad, Katrina; Phillips, David; Ranganathan, Dharani; Roberts, Thomas; Sanman, Ella; Vos, Theo; Wulf, Sarah] Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA.
[Couser, William; Ebel, Beth E.; Kassebaum, Nicholas; Mock, Charles; Olives, Casey; Rivara, Frederick P.; Vavilala, Monica S.] Univ Washington, Seattle, WA 98195 USA.
[Abraham, Jerry] Univ Texas San Antonio, Sch Med, San Antonio, TX USA.
[Omer, Saad B.; Steenland, Kyle] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.
[Ali, Mohammed K.; Dabhadkar, Kaustubh C.; Narayan, K. M. Venkat; Zabetian, Azadeh] Emory Univ, Atlanta, GA 30322 USA.
[Baddour, Larry M.; Gabriel, Sherine E.] Mayo Clin, Rochester, MN USA.
[Danaei, Goodarz; Ding, Eric L.; Finucane, Mariel M.; Khatibzadeh, Shahab; Knowlton, Lisa Marie; Lin, John Kent; Lu, Yuan; Singh, Gitanjali M.; Tavakkoli, Mohammad; Weisskopf, Marc G.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Bartels, David H.; Jayaraman, Sudha; Mozaffarian, Dariush] Harvard Univ, Sch Med, Boston, MA USA.
[Bhalla, Kavi] Harvard Univ, Boston, MA 02115 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Felson, David T.] Boston Univ, Boston, MA 02215 USA.
[Birbeck, Gretchen] Michigan State Univ, E Lansing, MI USA.
[Chen, Honglei; London, Stephanie] NIEHS, Res Triangle Pk, NC 27709 USA.
[Lan, Qing] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Grant, Bridget; Hoffman, Howard; Mensah, George A.] NIH, Bethesda, MD 20892 USA.
[Nelson, Robert G.] Natl Inst Diabet & Digest & Kidney Dis, Bethesda, MD USA.
[Wagner, Gregory R.] NIOSH, Baltimore, MD USA.
[Chugh, Sumeet S.; Havmoeller, Rasmus] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
[Havmoeller, Rasmus] Karolinska Inst, Stockholm, Sweden.
[Cohen, Aaron] Hlth Effects Inst, Boston, MA USA.
[Cooper, Leslie T.] Loyola Univ, Sch Med, Chicago, IL 60611 USA.
[Criqui, Michael H.] Univ Calif San Diego, La Jolla, CA 92093 USA.
[Dahodwala, Nabila; Silberberg, Donald] Univ Penn, Philadelphia, PA 19104 USA.
[Dellavalle, Robert P.] Denver VA Med Ctr, Denver, CO USA.
[Des Jarlais, Don C.] Beth Israel Deaconess Med Ctr, New York, NY 10003 USA.
[Dorsey, Ray; Shivakoti, Rupak] Johns Hopkins Univ, Baltimore, MD USA.
[Ezzati, Majid] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostatist, MRC HPA Ctr Environm & Hlth, London, England.
[Flaxman, Seth] Carnegie Mellon Univ, Pittsburgh, PA 15213 USA.
[Gillum, Richard F.] Howard Univ, Coll Med, Washington, DC USA.
[Gosselin, Richard] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Gutierrez, Hialy R.] Mailman Sch Publ Hlth, New York, NY USA.
[Moran, Andrew E.] Columbia Univ, New York, NY USA.
[Hagan, Holly; Thurston, George D.] NYU, New York, NY USA.
[Jacobsen, Kathryn H.] George Mason Univ, Fairfax, VA 22030 USA.
[Leasher, Janet L.] Nova SE Univ, Ft Lauderdale, FL 33314 USA.
[Lipshultz, Steven E.; Sacco, Ralph L.; Wilkinson, James D.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
[Lopez, Alan D.] Univ Melbourne, Sch Populat & Global Hlth, Melbourne, Vic, Australia.
[Lozano, Rafael] Inst Nacl Salud Publ, Ctr Invest Sistemas Salud, Cuernavaca, Morelos, Mexico.
[McDermott, Mary M.] Northwestern Univ, Feinberg Sch Med, Evanston, IL USA.
[Meltzer, Michele] Thomas Jefferson Univ, Philadelphia, PA 19107 USA.
[Michaud, Catherine] China Med Board, Boston, MA USA.
[Miller, Ted R.] Pacific Inst Res & Evaluat, Calverton, MD USA.
[Moffitt, Terrie E.] Duke Univ, Durham, NC USA.
[Mozaffarian, Dariush] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Ostro, Bart] Calif Environm Protect Agcy, Sacramento, CA USA.
[Pelizzari, Pamela M.] Ctr Medicare & Medicaid Serv, Baltimore, MD USA.
[Pope, C. Arden, III] Brigham Young Univ, Provo, UT 84602 USA.
[Raju, Murugesan] Univ Missouri, Mason Eye Inst, Columbia, MO 65211 USA.
[Razavi, Homie] Ctr Dis Anal, Louisville, CO USA.
[Ritz, Beate] Univ Calif Los Angeles, Los Angeles, CA USA.
[Sampson, Uchechukwu] Vanderbilt Univ, Nashville, TN 37235 USA.
[Sapkota, Amir] Univ Maryland, Sch Publ Hlth, College Pk, MD 20742 USA.
[Schwebel, David C.; Singh, Jasvinder A.] Univ Alabama Birmingham, Birmingham, AL USA.
[Shahraz, Saeid] Brandeis Univ, Waltham, MA USA.
[Shibuya, Kenji] Univ Tokyo, Dept Global Hlth Policy, Tokyo, Japan.
[Singh, David] Queens Med Ctr, Honolulu, HI USA.
[Sleet, David A.] Natl Ctr Injury Prevent & Control, Atlanta, GA USA.
[Taylor, Jennifer A.] Drexel Univ, Sch Publ Hlth, Philadelphia, PA 19104 USA.
[Towbin, Jeffrey A.] Cincinnati Childrens Hosp, Cincinnati, OH USA.
[Weinstock, Martin A.] Brown Univ, Providence, RI 02912 USA.
RP Murray, CJL (reprint author), Inst Hlth Metr & Evaluat, 2301 5th Ave,Ste 600, Seattle, WA 98121 USA.
EM cjlm@uw.edu
RI Lopez, Alan D/F-1487-2010; Dellavalle, Robert/L-2020-2013; Moffitt,
Terrie/D-5295-2011; Narayan, K.M. Venkat /J-9819-2012; Ritz,
Beate/E-3043-2015; Sapkota, Amir/A-5968-2011; Bolliger, Ian/C-4207-2016;
Jacobsen, Kathryn/B-5857-2008; Salomon, Joshua/D-3898-2009;
OI Chen, Honglei/0000-0003-3446-7779; London,
Stephanie/0000-0003-4911-5290; Lopez, Alan D/0000-0001-5818-6512; Mock,
Charles/0000-0002-0564-568X; Ding, Eric/0000-0002-5881-8097; singh,
jasvinder/0000-0003-3485-0006; Johns, Nicole/0000-0003-4513-4582;
Mensah, George/0000-0002-0387-5326; Benjamin,
Emelia/0000-0003-4076-2336; Miller, Ted/0000-0002-0958-2639; Dellavalle,
Robert/0000-0001-8132-088X; Moffitt, Terrie/0000-0002-8589-6760;
Narayan, K.M. Venkat /0000-0001-8621-5405; Bolliger,
Ian/0000-0001-8055-297X; Jacobsen, Kathryn/0000-0002-4198-6246; Salomon,
Joshua/0000-0003-3929-5515; Pelizzari, Pamela/0000-0002-6992-9462;
Ranganathan, Dharani/0000-0001-6506-2825
FU National Institutes of Health, the National Institute of Environmental
Health Sciences; Bill and Melinda Gates Foundation
FX This study is supported in part by the Intramural Program of the
National Institutes of Health, the National Institute of Environmental
Health Sciences, and in part by the Bill and Melinda Gates Foundation.
NR 81
TC 551
Z9 556
U1 40
U2 252
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD AUG 14
PY 2013
VL 310
IS 6
BP 591
EP 608
DI 10.1001/jama.2013.13805
PG 18
WC Medicine, General & Internal
SC General & Internal Medicine
GA 200HI
UT WOS:000323058400015
PM 23842577
ER
PT J
AU Nablo, BJ
Panchal, RG
Bavari, S
Nguyen, TL
Gussio, R
Ribot, W
Friedlander, A
Chabot, D
Reiner, JE
Robertson, JWF
Balijepalli, A
Halverson, KM
Kasianowicz, JJ
AF Nablo, Brian J.
Panchal, Rekha G.
Bavari, Sina
Nguyen, Tam L.
Gussio, Rick
Ribot, Wil
Friedlander, Art
Chabot, Donald
Reiner, Joseph E.
Robertson, Joseph W. F.
Balijepalli, Arvind
Halverson, Kelly M.
Kasianowicz, John J.
TI Anthrax toxin-induced rupture of artificial lipid bilayer membranes
SO JOURNAL OF CHEMICAL PHYSICS
LA English
DT Article
ID SYMMETRICAL TETRAALKYLAMMONIUM IONS; IRREVERSIBLE ELECTRICAL BREAKDOWN;
STERIC-BLOCK OLIGONUCLEOTIDES; CELL PENETRATING PEPTIDES; EFFICIENT
GENE-TRANSFER; PROTECTIVE ANTIGEN; BACILLUS-ANTHRACIS; LETHAL FACTOR;
PROTEIN TRANSLOCATION; EDEMA FACTOR
AB We demonstrate experimentally that anthrax toxin complexes rupture artificial lipid bilayer membranes when isolated from the blood of infected animals. When the solution pH is temporally acidified to mimic that process in endosomes, recombinant anthrax toxin forms an irreversibly bound complex, which also destabilizes membranes. The results suggest an alternative mechanism for the translocation of anthrax toxin into the cytoplasm.
C1 [Nablo, Brian J.; Reiner, Joseph E.; Robertson, Joseph W. F.; Balijepalli, Arvind; Kasianowicz, John J.] NIST, Phys Measurement Lab, Gaithersburg, MD 20899 USA.
[Panchal, Rekha G.; Bavari, Sina; Ribot, Wil; Friedlander, Art; Chabot, Donald; Halverson, Kelly M.] US Army Med Res Inst Infect Dis, Frederick, MD 21702 USA.
[Nguyen, Tam L.; Gussio, Rick] NCI, Dev Therapeut Program, Target Struct Based Drug Discovery Grp, SAIC, Frederick, MD 21702 USA.
[Balijepalli, Arvind] NHLBI, Lab Computat Biol, Rockville, MD 20852 USA.
RP Kasianowicz, JJ (reprint author), NIST, Phys Measurement Lab, Gaithersburg, MD 20899 USA.
EM john.kasianowicz@nist.gov
OI Reiner, Joseph/0000-0002-1056-8703
FU NIST-NRC; NIH-NIST-NRC; NIST Office of Law Enforcement Standards
FX This work is supported, in part, by a NIST-NRC Research Associateship
(B.J.N.), a NIH-NIST-NRC Research Associateship (A.B.), and the NIST
Office of Law Enforcement Standards (J.J.K.). Certain commercial
equipment, instruments, or materials are identified in this paper to
adequately specify the experimental procedure. Such identification does
not imply recommendation or endorsement by the National Institute of
Standards and Technology, nor does it imply that the materials or
equipment identified are necessarily the best available for the purpose.
In conducting the research described in this paper, the investigators
adhered to the "Guide for Care and Use of Laboratory Animals" as
promulgated by the Committee on Care and Use of Laboratory Animals of
the Institute of Laboratory Animal Resources, National Research Council.
The facilities are fully accredited by the American Association for
Accreditation of Laboratory Animal Care.
NR 130
TC 6
Z9 6
U1 3
U2 16
PU AMER INST PHYSICS
PI MELVILLE
PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA
SN 0021-9606
EI 1089-7690
J9 J CHEM PHYS
JI J. Chem. Phys.
PD AUG 14
PY 2013
VL 139
IS 6
AR 065101
DI 10.1063/1.4816467
PG 12
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 201YB
UT WOS:000323177900055
PM 23947891
ER
PT J
AU Shipman, SL
Herring, BE
Suh, YH
Roche, KW
Nicoll, RA
AF Shipman, Seth L.
Herring, Bruce E.
Suh, Young Ho
Roche, Katherine W.
Nicoll, Roger A.
TI Distance-Dependent Scaling of AMPARs Is Cell-Autonomous and GluA2
Dependent
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID CA1 PYRAMIDAL NEURONS; RECEPTOR TRAFFICKING; HIPPOCAMPAL-NEURONS;
SUBUNIT COMPOSITION; CORNICHON PROTEINS; SYNAPSES; PLASTICITY;
AMPLITUDE; REQUIRES; NUMBER
AB The extensive dendritic arbor of a pyramidal cell introduces considerable complexity to the integration of synaptic potentials. Propagation of dendritic potentials is largely passive, in contrast to regenerative axonal potentials that are maintained by voltage-gated sodium channels, leading to a declination in amplitude as dendritic potentials travel toward the soma in a manner that disproportionally affects distal synaptic inputs. To counteract this amplitude filtering, Schaffer collateral synapses onto CA1 pyramidal cells contain a varying number of AMPA receptors (AMPARs) per synapse that increases with distance from the soma, a phenomenon known as distance-dependent scaling. Here, we undertake an investigation into the molecular mechanisms of distance-dependent scaling. Using dendritic recordings from rat pyramidal neurons, we confirm the basic scaling phenomenon and find that it is expressed and can be manipulated cell autonomously. Finally, we show that it depends on the presence of both a reserve pool of AMPARs and the AMPAR subunit GluA2.
C1 [Shipman, Seth L.; Herring, Bruce E.; Nicoll, Roger A.] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA.
[Shipman, Seth L.; Herring, Bruce E.; Nicoll, Roger A.] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94158 USA.
[Shipman, Seth L.] Univ Calif San Francisco, Neurosci Grad Program, San Francisco, CA 94158 USA.
[Suh, Young Ho; Roche, Katherine W.] NINDS, US NIH, Bethesda, MD 20892 USA.
RP Nicoll, RA (reprint author), Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, 600 16th St,Genentech Hall N272D, San Francisco, CA 94158 USA.
EM roger.nicoll@ucsf.edu
OI Roche, Katherine/0000-0001-7282-6539
FU U.S. National Institute of Mental Health [R37 MH038256-29]; National
Institute of Neurological Disorders and Stroke
FX This work was supported by a grant from the U.S. National Institute of
Mental Health (R37 MH038256-29), and by the Intramural Research Program
of National Institute of Neurological Disorders and Stroke (Y.H.S. and
K.W.R.). We are grateful to Dan Johnston and the members of his
laboratory, specifically Darrin Brager and Rishi Narayanan, for
assistance with dendritic recording methodology.
NR 27
TC 9
Z9 9
U1 1
U2 9
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD AUG 14
PY 2013
VL 33
IS 33
BP 13312
EP 13319
DI 10.1523/JNEUROSCI.0678-13.2013
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 201PV
UT WOS:000323155700006
PM 23946389
ER
PT J
AU Murnane, KS
Winschel, J
Schmidt, KT
Stewart, LM
Rose, SJ
Cheng, KJ
Rice, KC
Howell, LL
AF Murnane, Kevin S.
Winschel, Jake
Schmidt, Karl T.
Stewart, LaShaya M.
Rose, Samuel J.
Cheng, Kejun
Rice, Kenner C.
Howell, Leonard L.
TI Serotonin 2A Receptors Differentially Contribute to Abuse-Related
Effects of Cocaine and Cocaine-Induced Nigrostriatal and Mesolimbic
Dopamine Overflow in Nonhuman Primates
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID VENTRAL TEGMENTAL AREA; MEDIAL PREFRONTAL CORTEX; CONSCIOUS
RHESUS-MONKEYS; SEEKING BEHAVIOR; 3,4-METHYLENEDIOXYMETHAMPHETAMINE
MDMA; INDUCED REINSTATEMENT; 5-HT2A RECEPTORS; DORSAL STRIATUM; RELEASE;
DRUG
AB Two of the most commonly used procedures to study the abuse-related effects of drugs in laboratory animals are intravenous drug self-administration and reinstatement of extinguished behavior previously maintained by drug delivery. Intravenous self-administration is widely accepted to model ongoing drug-taking behavior, whereas reinstatement procedures are accepted to model relapse to drug taking following abstinence. Previous studies indicate that 5-HT2A receptor antagonists attenuate the reinstatement of cocaine-maintained behavior but not cocaine self-administration in rodents. Although the abuse-related effects of cocaine have been closely linked to brain dopamine systems, no previous study has determined whether this dissociation is related to differential regulation of dopamine neurotransmission. To elucidate the neuropharmacological and neuroanatomical mechanisms underlying this phenomenon, we evaluated the effects of the selective 5-HT2A receptor antagonist M100907 on intravenous cocaine self-administration and drug- and cue-primed reinstatement in rhesus macaques (Macaca mulatta). In separate subjects, we evaluated the role of 5-HT2A receptors in cocaine-induced dopamine overflow in the nucleus accumbens (n = 4) and the caudate nucleus (n = 5) using in vivo microdialysis. Consistent with previous studies, M100907 (0.3 mg/kg, i.m.) significantly attenuated drug-and cue-induced reinstatement but had no significant effects on cocaine self-administration across a range of maintenance doses. Importantly, M100907 (0.3 mg/kg, i.m.) attenuated cocaine-induced (1.0 mg/kg, i.v.) dopamine overflow in the caudate nucleus but not in the nucleus accumbens. These data suggest that important abuse-related effects of cocaine are mediated by distinct striatal dopamine projection pathways.
C1 [Murnane, Kevin S.; Winschel, Jake; Schmidt, Karl T.; Stewart, LaShaya M.; Rose, Samuel J.; Howell, Leonard L.] Emory Univ, Yerkes Natl Primate Res Ctr, Div Neuropharmacol & Neurol Dis, Atlanta, GA 30322 USA.
[Howell, Leonard L.] Emory Univ, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA.
[Cheng, Kejun; Rice, Kenner C.] NIDA, Chem Biol Res Branch, Bethesda, MD 20892 USA.
[Cheng, Kejun; Rice, Kenner C.] NIAAA, NIH, Bethesda, MD 20892 USA.
RP Howell, LL (reprint author), Emory Univ, Yerkes Natl Primate Res Ctr, 954 Gatewood Rd, Atlanta, GA 30322 USA.
EM lhowell@emory.edu
FU United States Public Health Service [DA010344, DA012514, RR00165];
National Institutes of Health Office of Research Infrastructure Programs
[0DP510D11132]; National Institute on Drug Abuse; National Institute on
Alcohol Abuse and Alcoholism
FX These studies were supported by United States Public Health Service
Grants DA010344, DA012514, and RR00165, and is currently supported by
the National Institutes of Health Office of Research Infrastructure
Programs Grant 0DP510D11132. A portion of this work was supported by the
Intramural Research Programs of the National Institute on Drug Abuse and
the National Institute on Alcohol Abuse and Alcoholism. We thank both
Juliet Brown and Lisa Neidert for their expert technical assistance.
NR 52
TC 13
Z9 13
U1 0
U2 2
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 AUG 14
PY 2013
VL 33
IS 33
BP 13367
EP 13374
DI 10.1523/JNEUROSCI.1437-13.2013
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 201PV
UT WOS:000323155700011
PM 23946394
ER
PT J
AU Chen, K
Tjandra, N
AF Chen, Kang
Tjandra, Nico
TI Determining Interdomain Structure and Dynamics of a Retroviral Capsid
Protein in the Presence of Oligomerization: Implication for Structural
Transition in Capsid Assembly
SO BIOCHEMISTRY
LA English
DT Article
ID RESIDUAL DIPOLAR COUPLINGS; ROTATIONAL DIFFUSION TENSOR; NMR STRUCTURE
DETERMINATION; INFECTIOUS-ANEMIA VIRUS; N-TERMINAL DOMAIN; MULTIDOMAIN
PROTEINS; GLOBULAR-PROTEINS; RELAXATION RATES; MOLECULAR SHAPE; IN-VITRO
AB Capsid (CA) proteins from all retroviruses, including HIV-1, are structurally homologous dual-domain helical proteins. They form a capsid lattice composed of unitary symmetric CA hexamers. X-ray crystallography has shown that within each hexamer a monomeric CA adopts a single conformation, where most helices are parallel to the symmetry axis. In solution, large differences in averaged NMR spin relaxation rates for the two domains were observed, suggesting they are dynamically independent. One relevant question for the capsid assembly remains: whether the interdomain conformer within a hexamer unit needs to be induced or pre-exists within the conformational space of a monomeric CA. The latter seems more consistent with the relaxation data. However, possible CA protein oligomerization and the structure of each domain will affect relaxation measurements and data interpretation. This study, using CA proteins from equine infectious anemia virus (EIAV) as an example, demonstrates a linear extrapolation approach to obtain backbone N-15 spin relaxation time ratios T-1/T-2 for a monomeric EIAV-CA in the presence of oligomerization equilibrium. The interdomain motion turns out to be limited. The large difference in the domain averaged < T-1/T-2 > for a CA monomer is a consequence of the orthogonal distributions of helices in the two domains. The new monomeric interdomain conformation in solution is significantly different from that in CA hemmer. Therefore, if capsid assembly follows a nucleation propagation process, the interdomain conformational change might be a key step during the nucleation, as the configuration in hexagonal assembly is never formed by diffusion of its two domains in solution.
C1 [Chen, Kang; Tjandra, Nico] NHLBI, Lab Mol Biophys, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA.
RP Tjandra, N (reprint author), NHLBI, Lab Mol Biophys, Biochem & Biophys Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM tjandran@nhlbi.nih.gov
FU National Heart, Lung, and Blood Institute of the NIH
FX The project was funded by the Intramural Research Programs of the
National Heart, Lung, and Blood Institute of the NIH.
NR 51
TC 3
Z9 3
U1 0
U2 20
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD AUG 13
PY 2013
VL 52
IS 32
BP 5365
EP 5371
DI 10.1021/bi400592d
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 202DM
UT WOS:000323193700006
PM 23906107
ER
PT J
AU Marine, JE
Shetty, V
Chow, GV
Wright, JG
Gerstenblith, G
Najjar, SS
Lakatta, EG
Fleg, JL
AF Marine, Joseph E.
Shetty, Veena
Chow, Grant V.
Wright, Jeanette G.
Gerstenblith, Gary
Najjar, Samer S.
Lakatta, Edward G.
Fleg, Jerome L.
TI Prevalence and Prognostic Significance of Exercise-Induced Nonsustained
Ventricular Tachycardia in Asymptomatic Volunteers BLSA (Baltimore
Longitudinal Study of Aging)
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE aging; exercise testing; ventricular tachycardia
ID CARDIOVASCULAR-DISEASE ENTERPRISES; APPARENTLY HEALTHY-VOLUNTEERS;
HYPERTROPHIC CARDIOMYOPATHY; MAJOR SHAREHOLDERS; SUDDEN-DEATH; HUMAN
HEART; RISK; ARRHYTHMIAS; PREDICTOR; ARTERIAL
AB Objectives This study sought to determine the clinical predictors and prognostic significance of exercise-induced nonsustained ventricular tachycardia (NSVT) in a large population of asymptomatic volunteers.
Background Prior studies have reported variable risk associated with exercise-induced ventricular arrhythmia.
Methods Subjects in the BLSA (Baltimore Longitudinal Study of Aging) free of known cardiovascular disease who completed at least 1 symptom-limited exercise treadmill test between 1977 and 2001 were included. NSVT episodes were characterized by QRS morphology, duration, and rate. Subjects underwent follow-up clinical evaluation every 2 years.
Results The 2,099 subjects (mean age: 52 years; 52.2% male) underwent a mean of 2.7 exercise tests, in which 79 (3.7%) developed NSVT with exercise on at least 1 test. The median duration of NSVT was 3 beats (<= 5 beats in 84%), and the median rate was 175 beats/min. Subjects with (vs. without) NSVT were older (67 +/- 12 years vs. 51 +/- 17 years, p < 0.0001) and more likely to be male (80% vs. 51%, p < 0.0001) and to have baseline electrocardiographic abnormalities (50% vs. 17%, p < 0.0001) or ischemic ST-segment changes with exercise (20% vs. 10%, p = 0.004). Over a mean follow-up of 13.5 +/- 7.7 years, 518 deaths (24.6%) occurred. After multivariable adjustment for age, sex, and coronary risk factors, exercise-induced NSVT was not significantly associated with total mortality (hazard ratio: 1.30; 95% confidence interval: 0.89 to 1.90; p = 0.17).
Conclusions Exercise-induced NSVT occurred in nearly 4% of this asymptomatic adult cohort. This finding increased with age and was more common in men. After adjustment for clinical variables, exercise-induced NSVT did not independently increase the risk of total mortality. (C) 2013 by the American College of Cardiology Foundation
C1 [Marine, Joseph E.; Chow, Grant V.; Gerstenblith, Gary] Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA.
[Shetty, Veena; Wright, Jeanette G.; Najjar, Samer S.; Lakatta, Edward G.] NIA, Baltimore, MD 21224 USA.
[Najjar, Samer S.] Washington Hosp Ctr, MedStar Hlth Res Inst, Washington, DC 20010 USA.
[Fleg, Jerome L.] NHLBI, Bethesda, MD 20892 USA.
RP Fleg, JL (reprint author), NHLBI, Div Cardiovasc Sci, 6701 Rockledge Dr,Room 8147, Bethesda, MD 20892 USA.
EM flegj@nhlbi.nih.gov
FU National Institute on Aging of the National Institutes of Health;
MedStar Research Institute; HeartWare Inc.
FX This research was supported in part by the Intramural Research Program
of the National Institute on Aging of the National Institutes of Health
and the MedStar Research Institute. Dr. Najjar has received research
support from HeartWare Inc. All other authors have reported that they
have no relationships relevant to the content of this paper to disclose.
NR 19
TC 12
Z9 13
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD AUG 13
PY 2013
VL 62
IS 7
BP 595
EP 600
DI 10.1016/j.jacc.2013.05.026
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 207MQ
UT WOS:000323605200006
PM 23747767
ER
PT J
AU Liao, QH
Bai, T
Zhou, L
Vong, S
Guo, JQ
Lv, W
Dong, LB
Xiang, NJ
Li, Z
Huai, Y
Zhou, JF
Li, XD
Chen, RY
Xu, Z
Uyeki, TM
Shu, YL
Yu, H
AF Liao, Qiaohong
Bai, Tian
Zhou, Lei
Vong, Sirenda
Guo, Junqiao
Lv, Wei
Dong, Libo
Xiang, Nijuan
Li, Zi
Huai, Yang
Zhou, Jianfang
Li, Xiaodan
Chen, Ray Y.
Xu, Zhen
Uyeki, Timothy M.
Shu, Yuelong
Yu, Hongjie
TI Seroprevalence of Antibodies to Highly Pathogenic Avian Influenza A
(H5N1) Virus among Close Contacts Exposed to H5N1 Cases, China,
2005-2008
SO PLOS ONE
LA English
DT Article
AB To assess the extent of highly pathogenic avian influenza (HPAI) A (H5N1) virus transmission, we conducted sero-epidemiologic studies among close contacts exposed to H5N1 cases in mainland China during 2005-2008. Blood specimens were collected from 87 household members and 332 social contacts of 23 H5N1 index cases for HPAI H5N1 serological testing by modified horse red-blood-cell hemagglutinin inhibition and microneutralization assays. All participants were interviewed with a standardized questionnaire to collect information about the use of personal protective equipment, illness symptoms, exposure to an H5N1 case during the infectious period, and poultry exposures. Two (2.3%) household contacts tested positive for HPAI H5N1 virus antibody, and all social contacts tested negative. Both seropositive cases had prolonged, unprotected, close contact with a different H5N1 index case, including days of bed-care or sleeping together during the index case's infectious period, and did not develop any illness. None of the 419 close contacts used appropriate personal protective equipment including 17% who reported providing bedside care or having physical contact with an H5N1 case for at least 12 hours. Our findings suggest that HPAI H5N1 viruses that circulated among poultry in mainland China from 2005-2008 were not easily transmitted to close contacts of H5N1 cases.
C1 [Liao, Qiaohong; Xu, Zhen; Yu, Hongjie] Chinese Ctr Dis Control & Prevent China CDC, Div Infect Dis, Key Lab Surveillance & Early Warning Infect Dis, Beijing, Peoples R China.
[Bai, Tian; Dong, Libo; Li, Zi; Zhou, Jianfang; Li, Xiaodan; Shu, Yuelong] Natl Hlth & Family Planning Commiss, Natl Inst Viral Dis Control & Prevent Chinese, Chinese Ctr Dis Control & Prevent, Key Lab Med Virol, Beijing, Peoples R China.
[Zhou, Lei; Xiang, Nijuan] China CDC, Publ Hlth Emergency Ctr, Beijing, Peoples R China.
[Vong, Sirenda] World Hlth Org WHO Beijing Off, Beijing, Peoples R China.
[Guo, Junqiao] Liaoning Ctr Dis Control & Prevent, Shenyang, Liaoning, Peoples R China.
[Lv, Wei] Guangxi Ctr Dis Control & Prevent, Nanning, Guangxi, Peoples R China.
[Huai, Yang] US Ctr Dis Control & Prevent, Int Emerging Infect Program, Beijing, Peoples R China.
[Chen, Ray Y.] NIAID, NIH, Bethesda, MD 20892 USA.
[Uyeki, Timothy M.] Ctr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA USA.
RP Shu, YL (reprint author), Natl Hlth & Family Planning Commiss, Natl Inst Viral Dis Control & Prevent Chinese, Chinese Ctr Dis Control & Prevent, Key Lab Med Virol, Beijing, Peoples R China.
EM yshu@cnic.org.cn; yuhj@chinacdc.cn
OI Chen, Ray/0000-0001-6344-1442
FU National Institute of Allergy and Infectious Diseases (NIAID); U.S.
National Institutes of Health [U19 AI51915]; Ministry of Science and
Technology (MOST) of the People's Republic of China [2004BA519A71,
2006BAD06A02]
FX This study was supported by grants from the National Institute of
Allergy and Infectious Diseases (NIAID), U.S. National Institutes of
Health (Comprehensive International Program for Research on AIDS grant
U19 AI51915, http://www.niaid.nih.gov/Pages/default.aspx), and from the
Ministry of Science and Technology (MOST) of the People's Republic of
China (2004BA519A71 and 2006BAD06A02, http://www.most.gov.cn/). The
NIAID was involved in the study design, data interpretation, and review
and approval of the manuscript. The China MOST had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript. The views expressed in this study are
those of the authors and do not represent the policy of their
institutions.
NR 45
TC 3
Z9 3
U1 2
U2 10
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 13
PY 2013
VL 8
IS 8
AR e71765
DI 10.1371/journal.pone.0071765
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 201BN
UT WOS:000323115800078
PM 23967241
ER
PT J
AU Trabzuni, D
Ryten, M
Emmett, W
Ramasamy, A
Lackner, KJ
Zeller, T
Walker, R
Smith, C
Lewis, PA
Mamais, A
de Silva, R
Vandrovcova, J
Hernandez, D
Nalls, MA
Sharma, M
Garnier, S
Lesage, S
Simon-Sanchez, J
Gasser, T
Heutink, P
Brice, A
Singleton, A
Cai, HB
Schadt, E
Wood, NW
Bandopadhyay, R
Weale, ME
Hardy, J
Plagnol, V
AF Trabzuni, Daniah
Ryten, Mina
Emmett, Warren
Ramasamy, Adaikalavan
Lackner, Karl J.
Zeller, Tanja
Walker, Robert
Smith, Colin
Lewis, Patrick A.
Mamais, Adamantios
de Silva, Rohan
Vandrovcova, Jana
Hernandez, Dena
Nalls, Michael A.
Sharma, Manu
Garnier, Sophie
Lesage, Suzanne
Simon-Sanchez, Javier
Gasser, Thomas
Heutink, Peter
Brice, Alexis
Singleton, Andrew
Cai, Huaibin
Schadt, Eric
Wood, Nicholas W.
Bandopadhyay, Rina
Weale, Michael E.
Hardy, John
Plagnol, Vincent
CA Int Parkinson Dis Genomics
TI Fine-Mapping, Gene Expression and Splicing Analysis of the Disease
Associated LRRK2 Locus
SO PLOS ONE
LA English
DT Article
AB Association studies have identified several signals at the LRRK2 locus for Parkinson's disease (PD), Crohn's disease (CD) and leprosy. However, little is known about the molecular mechanisms mediating these effects. To further characterize this locus, we fine-mapped the risk association in 5,802 PD and 5,556 controls using a dense genotyping array (ImmunoChip). Using samples from 134 post-mortem control adult human brains (UK Human Brain Expression Consortium), where up to ten brain regions were available per individual, we studied the regional variation, splicing and regulation of LRRK2. We found convincing evidence for a common variant PD association located outside of the LRRK2 protein coding region (rs117762348, A>G, P = 2.56 x 10(-8), case/control MAF 0.083/0.074, odds ratio 0.86 for the minor allele with 95% confidence interval [0.80-0.91]). We show that mRNA expression levels are highest in cortical regions and lowest in cerebellum. We find an exon quantitative trait locus (QTL) in brain samples that localizes to exons 32-33 and investigate the molecular basis of this eQTL using RNA-Seq data in n = 8 brain samples. The genotype underlying this eQTL is in strong linkage disequilibrium with the CD associated non-synonymous SNP rs3761863 (M2397T). We found two additional QTLs in liver and monocyte samples but none of these explained the common variant PD association at rs117762348. Our results characterize the LRRK2 locus, and highlight the importance and difficulties of fine-mapping and integration of multiple datasets to delineate pathogenic variants and thus develop an understanding of disease mechanisms.
C1 [Trabzuni, Daniah; Ryten, Mina; Lewis, Patrick A.; Mamais, Adamantios; de Silva, Rohan; Vandrovcova, Jana; Wood, Nicholas W.; Bandopadhyay, Rina; Hardy, John] UCL Inst Neurol, Dept Mol Neurosci, London, England.
[Trabzuni, Daniah] King Faisal Specialist Hosp & Res Ctr, Dept Genet, Riyadh 11211, Saudi Arabia.
[Emmett, Warren; Plagnol, Vincent] UCL, Genet Inst, London, England.
[Ramasamy, Adaikalavan; Weale, Michael E.] Kings Coll London, Guys Hosp, Dept Med & Mol Genet, London, England.
[Lackner, Karl J.] Univ Med Ctr Mainz, Inst Clin Chem & Lab Med, Mainz, Germany.
[Zeller, Tanja] Univ Heart Ctr Hamburg, Clin Gen & Intervent Cardiol, Hamburg, Germany.
[Walker, Robert; Smith, Colin] Univ Edinburgh, Dept Neuropathol, MRC Sudden Death Brain Bank Project, Edinburgh, Midlothian, Scotland.
[Lewis, Patrick A.] Univ Reading, Sch Pharm, Reading, Berks, England.
[Mamais, Adamantios; de Silva, Rohan; Vandrovcova, Jana; Bandopadhyay, Rina; Hardy, John] Reta Lila Weston Inst Neurol Studies, London, England.
[Hernandez, Dena; Nalls, Michael A.; Singleton, Andrew] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Sharma, Manu; Gasser, Thomas] Univ Tubingen, Hertie Inst Clin Brain Res, Div Neurodegenerat Disorders, Tubingen, Germany.
[Garnier, Sophie] Univ Paris 06, INSERM, UMRS 937, Paris, France.
[Lesage, Suzanne; Brice, Alexis] Univ Paris 06, CRICM, CNRS,UMR 7225, INSERM,Hosp Pitie Salpetriere,UMRS 975, Paris, France.
[Simon-Sanchez, Javier; Heutink, Peter] Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, Sect Med Genom, Amsterdam, Netherlands.
[Cai, Huaibin] NIA, Unit Transgenesis, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Schadt, Eric] Mt Sinai Sch Med, Inst Genom & Multiscale Biol, New York, NY USA.
RP Plagnol, V (reprint author), UCL, Genet Inst, London, England.
EM v.plagnol@ucl.ac.uk
RI Hardy, John/C-2451-2009; Lewis , Patrick/C-3674-2009; Singleton,
Andrew/C-3010-2009; Trabzuni, Daniah/C-4034-2012; Weale,
Michael/F-2587-2010; Bandopadhyay, Rina /C-7926-2009; de Silva,
Rohan/C-1734-2008; Ramasamy, Adaikalavan/G-2632-2010; Wood,
Nicholas/C-2505-2009;
OI Trabzuni, Daniah/0000-0003-4826-9570; Weale,
Michael/0000-0003-4593-1186; de Silva, Rohan/0000-0002-5052-5775;
Plagnol, Vincent/0000-0002-5597-9215; Lewis,
Patrick/0000-0003-4537-0489; Ramasamy, Adaikalavan/0000-0002-7598-2892;
Wood, Nicholas/0000-0002-9500-3348; Walker, Robert/0000-0001-7383-7846
FU Medical Research Council (MRC) through the MRC Sudden Death Brain Bank;
King Faisal Specialist Hospital and Research Centre, Saudi Arabia;
Michael J. Fox Foundation LRRK2 consortium grant; Wellcome Trust/MRC
Joint Call in Neurodegeneration award [WT089698]; Department of Health's
NIHR Biomedical Research Centres funding scheme; National Institute on
Aging; National Institute of Neurological Disorders and Stroke; National
Institute of Environmental Health Sciences; National Human Genome
Research Institute; National Institutes of Health; Department of Health
and Human Services [Z01 AG000949-02, Z01-ES101986]; US Department of
Defense [W81XWH-09-2-0128]; National Institutes of Health [NS057105,
RR024992]; American Parkinson Disease Association (APDA); Barnes Jewish
Hospital Foundation; Greater St. Louis Chapter of the APDA;
Forschungszentrumfur-Umwelt und Gesundheit (GSF); German Federal
Ministry of Education, Science, Research, and Technology; State of
Bavaria; German National Genome Network [01GS08134]; German Ministry for
Education and Research; German Federal Ministry of Education and
Research (BMBF) NGFN [01GR0468]; ERA-Net NEURON [01GW0908]; Helmholtz
Alliance Mental Health in an Ageing Society (HelMA) [HA-215]; Initiative
and Networking Fund of the Helmholtz Association; Hersenstichting
Nederland; Neuroscience Campus Amsterdam; section of Medical genomics,
the Prinses Beatrix Fonds; [G0901254]; [G0802462]; [F1002]
FX This work was supported by the Medical Research Council (MRC) through
the MRC Sudden Death Brain Bank (C. S.) and by a Project Grant (G0901254
to J.H. and M. W.) and Training Fellowship (G0802462 to M. R.). D. T.
was supported by the King Faisal Specialist Hospital and Research
Centre, Saudi Arabia. P. A. L. is a Parkinson's UK research fellow
(fellowship F1002). A. M. and C. M. are supported by a Michael J. Fox
Foundation LRRK2 consortium grant to P. A. L. and R. B. This work was
supported in part by the Wellcome Trust/MRC Joint Call in
Neurodegeneration award (WT089698) to the UK Parkinson's Disease
Consortium (UKPDC) whose members are from the UCL Institute of
Neurology, the University of Sheffield and the MRC Protein
Phosphorylation Unit at the University of Dundee. This work was
undertaken in part at UCLH/UCL who received a proportion of funding from
the Department of Health's NIHR Biomedical Research Centres funding
scheme. This US work was supported in part by the Intramural Research
Programs of the National Institute on Aging, National Institute of
Neurological Disorders and Stroke, National Institute of Environmental
Health Sciences, National Human Genome Research Institute, National
Institutes of Health, Department of Health and Human Services; project
numbers Z01 AG000949-02 and Z01-ES101986. In addition this study was
supported by the US Department of Defense, award number
W81XWH-09-2-0128. Funding to support collection of a portion of the
samples was obtained from the National Institutes of Health (grants
NS057105 and RR024992), the American Parkinson Disease Association
(APDA), Barnes Jewish Hospital Foundation, and the Greater St. Louis
Chapter of the APDA. The KORA research platform (KORA: Cooperative
Research in the Region of Augsburg; http://www.gsf.de/KORA) was
initiated and financed by the Forschungszentrumfur-Umwelt und Gesundheit
(GSF), which is funded by the German Federal Ministry of Education,
Science, Research, and Technology and by the State of Bavaria. The study
was additionally funded by the German National Genome Network (NGFNplus
#01GS08134; German Ministry for Education and Research) and by the
German Federal Ministry of Education and Research (BMBF) NGFN (01GR0468)
and in the frame of ERA-Net NEURON (01GW0908). This work was also
supported by the Helmholtz Alliance Mental Health in an Ageing Society
(HelMA, HA-215) funded by the Initiative and Networking Fund of the
Helmholtz Association. The authors also want to thank the
Hersenstichting Nederland (http://www.hersenstichting.nl), the
Neuroscience Campus Amsterdam and the section of Medical genomics, the
Prinses Beatrix Fonds (http://www.prinsesbeatrixfonds.nl) for sponsoring
this work. The authors have no conflicting financial, personal, or
professional interests. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 37
TC 11
Z9 11
U1 0
U2 19
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 AUG 13
PY 2013
VL 8
IS 8
AR e70724
DI 10.1371/journal.pone.0070724
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 201BN
UT WOS:000323115800015
PM 23967090
ER
PT J
AU Yang, YJ
Tao-Cheng, JH
Bayer, KU
Reese, TS
Dosemeci, A
AF Yang, Yijung
Tao-Cheng, Jung-Hwa
Bayer, K. Ulrich
Reese, Thomas S.
Dosemeci, Ayse
TI Camkii-Mediated Phosphorylation Regulates Distributions of Syngap-alpha
1 and -alpha 2 at the Postsynaptic Density
SO PLOS ONE
LA English
DT Article
AB SynGAP, a protein abundant at the postsynaptic density (PSD) of glutamatergic neurons, is known to modulate synaptic strength by regulating the incorporation of AMPA receptors at the synapse. Two isoforms of SynGAP, alpha 1 and alpha 2, which differ in their C-termini, have opposing effects on synaptic strength. In the present study, antibodies specific for SynGAP-alpha 1 and SynGAP-alpha 2 are used to compare the distribution patterns of the two isoforms at the postsynaptic density (PSD) under basal and excitatory conditions. Western immunoblotting shows enrichment of both isoforms in PSD fractions isolated from adult rat brain. Immunogold electron microscopy of rat hippocampal neuronal cultures shows similar distribution of both isoforms at the PSD, with a high density of immunolabel within the PSD core under basal conditions. Application of NMDA promotes movement of SynGAP-alpha 1 as well as SynGAP-alpha 2 out of the PSD core. In isolated PSDs both isoforms of SynGAP can be phosphorylated upon activation of the endogenous CaMKII. Application of tatCN21, a cell-penetrating inhibitor of CaMKII, to hippocampal neuronal cultures blocks NMDA-induced redistribution of SynGAP-alpha 1 and SynGAP-alpha 2. Thus CaMKII activation promotes the removal of two distinct C-terminal SynGAP variants from the PSD.
C1 [Yang, Yijung; Reese, Thomas S.; Dosemeci, Ayse] NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA.
[Tao-Cheng, Jung-Hwa] NINDS, EM Facil, NIH, Bethesda, MD 20892 USA.
[Bayer, K. Ulrich] Univ Colorado, Denver Sch Med, Dept Pharmacol, Aurora, CO USA.
RP Dosemeci, A (reprint author), NINDS, Neurobiol Lab, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM dosemeca@mail.nih.gov
FU NINDS, National Institutes of Health (NIH); NIH [R01 NS081248]
FX This research was supported by the Intramural Research Program NINDS,
National Institutes of Health (NIH) and NIH grant R01 NS081248 (to KUB).
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 29
TC 5
Z9 5
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 13
PY 2013
VL 8
IS 8
AR e71795
DI 10.1371/journal.pone.0071795
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 201BN
UT WOS:000323115800080
PM 23967245
ER
PT J
AU Gartner, JJ
Parker, SCJ
Prickett, TD
Dutton-Regester, K
Stitzel, ML
Lin, JC
Davis, S
Simhadri, VL
Jha, S
Katagiri, N
Gotea, V
Teer, JK
Wei, XM
Morken, MA
Bhanot, UK
Chen, G
Elnitski, LL
Davies, MA
Gershenwald, JE
Carter, H
Karchin, R
Robinson, W
Robinson, S
Rosenberg, SA
Collins, FS
Parmigiani, G
Komar, AA
Kimchi-Sarfaty, C
Hayward, NK
Margulies, EH
Samuels, Y
AF Gartner, Jared J.
Parker, Stephen C. J.
Prickett, Todd D.
Dutton-Regester, Ken
Stitzel, Michael L.
Lin, Jimmy C.
Davis, Sean
Simhadri, Vijaya L.
Jha, Sujata
Katagiri, Nobuko
Gotea, Valer
Teer, Jamie K.
Wei, Xiaomu
Morken, Mario A.
Bhanot, Umesh K.
Chen, Guo
Elnitski, Laura L.
Davies, Michael A.
Gershenwald, Jeffrey E.
Carter, Hannah
Karchin, Rachel
Robinson, William
Robinson, Steven
Rosenberg, Steven A.
Collins, Francis S.
Parmigiani, Giovanni
Komar, Anton A.
Kimchi-Sarfaty, Chava
Hayward, Nicholas K.
Margulies, Elliott H.
Samuels, Yardena
CA NISC Comparative Sequencing Progra
TI Whole-genome sequencing identifies a recurrent functional synonymous
mutation in melanoma
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID TERT PROMOTER MUTATIONS; HUMAN CANCER; POSITIVE SELECTION; EVOLUTION;
REVEALS; DISEASE; CONSTRAINT; SUBSTRATE; GENE; SITE
AB Synonymous mutations, which do not alter the protein sequence, have been shown to affect protein function [Sauna ZE, Kimchi-Sarfaty C (2011) Nat Rev Genet 12(10):683-691]. However, synonymous mutations are rarely investigated in the cancer genomics field. We used whole-genome and -exome sequencing to identify somatic mutations in 29 melanoma samples. Validation of one synonymous somatic mutation in BCL2L12 in 285 samples identified 12 cases that harbored the recurrent F17F mutation. This mutation led to increased BCL2L12 mRNA and protein levels because of differential targeting of WT and mutant BCL2L12 by hsa-miR-671-5p. Protein made from mutant BCL2L12 transcript bound p53, inhibited UV-induced apoptosis more efficiently than WT BCL2L12, and reduced endogenous p53 target gene transcription. This report shows selection of a recurrent somatic synonymous mutation in cancer. Our data indicate that silent alterations have a role to play in human cancer, emphasizing the importance of their investigation in future cancer genome studies.
C1 [Gartner, Jared J.; Parker, Stephen C. J.; Prickett, Todd D.; Stitzel, Michael L.; Gotea, Valer; Teer, Jamie K.; Wei, Xiaomu; Morken, Mario A.; Elnitski, Laura L.; Collins, Francis S.; Margulies, Elliott H.; Samuels, Yardena; NISC Comparative Sequencing Progra] NHGRI, Bethesda, MD 20892 USA.
[Davis, Sean; Rosenberg, Steven A.] NCI, NIH, Bethesda, MD 20892 USA.
[Dutton-Regester, Ken; Hayward, Nicholas K.] Queensland Inst Med Res, Div Genet & Computat Biol, Brisbane, Qld 4006, Australia.
[Lin, Jimmy C.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
[Simhadri, Vijaya L.; Katagiri, Nobuko; Kimchi-Sarfaty, Chava] US FDA, Lab Hemostasis, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
[Jha, Sujata; Komar, Anton A.] Cleveland State Univ, Ctr Gene Regulat Hlth & Dis, Cleveland, OH 44115 USA.
[Jha, Sujata; Komar, Anton A.] Cleveland State Univ, Dept Biol Geol & Environm Sci, Cleveland, OH 44115 USA.
[Bhanot, Umesh K.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA.
[Chen, Guo; Davies, Michael A.; Gershenwald, Jeffrey E.] Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Houston, TX 77030 USA.
[Carter, Hannah; Karchin, Rachel] Johns Hopkins Univ, Inst Computat Med, Dept Biomed Engn, Baltimore, MD 21218 USA.
[Robinson, William; Robinson, Steven] Univ Colorado, Sch Med, Div Med Oncol, Aurora, CO 80045 USA.
[Parmigiani, Giovanni] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Parmigiani, Giovanni] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Margulies, Elliott H.] Illumina United Kingdom, Saffron Walden CB10 1XL, Essex, England.
[Samuels, Yardena] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel.
RP Samuels, Y (reprint author), NHGRI, Bethesda, MD 20892 USA.
EM yardena.samuels@weizmann.ac.il
RI Karchin, Rachel/A-3385-2010; hayward, nicholas/C-1367-2015;
OI hayward, nicholas/0000-0003-4760-1033; Bhanot,
Umeshkumar/0000-0001-6656-1239; Davis, Sean/0000-0002-8991-6458; Gotea,
Valer/0000-0001-7857-3309
FU NIGMS Postdoctoral Research Associate (PRAT) Fellowship; Intramural
Research Programs of the National Human Genome Research Institute; Henry
Chanoch Krenter Institute for Biomedical Imaging and Genomics; estate of
Alice Schwarz-Gardos; estate of John Hunter; Knell Family; Peter and
Patricia Gruber Award; National Cancer Institute [R21CA152432]; National
Institutes of Health; University of Texas MD Anderson Cancer Center
Melanoma Specialized Programs of Research Excellence [P50 CA093459];
Cancer Center Support Grant (CCSG) Core Grant [NCI 5P30 CA006516-46];
Human Frontier Science Program [RGP0024]; National Health and Medical
Research Council of Australia [1026112, 613686]; National Cancer
Institute; Eli Lilly and Company
FX We thank Drs. Chris Schmidt and Peter Parsons for establishment of the
majority of melanoma cell lines and V. Maduro, H. Ozel Abaan, and P.
Cruz for generating the sequence data analyzed here. We thank Dr. V. G.
Prieto for pathologic review of the biospecimens from the Melanoma
Informatics, Tissue Resource, and Pathology Core (MelCore) at MD
Anderson. We thank Dr. T. Wolfsberg for bioinformatics help, J. Jiang
for sequencing help, and J. Fekecs and D. Leja for graphical assistance.
We thank Drs. T. Barber and M. Willard for critical comments on the
manuscript. S.C.J.P. is supported by an NIGMS Postdoctoral Research
Associate (PRAT) Fellowship. This work was supported by the Intramural
Research Programs of the National Human Genome Research Institute, by
the Henry Chanoch Krenter Institute for Biomedical Imaging and Genomics,
the estate of Alice Schwarz-Gardos, the estate of John Hunter, the Knell
Family, the Peter and Patricia Gruber Award, National Cancer Institute
Grant R21CA152432 (to R.K.), the National Institutes of Health,
University of Texas MD Anderson Cancer Center Melanoma Specialized
Programs of Research Excellence Grant P50 CA093459, Cancer Center
Support Grant (CCSG) Core Grant NCI 5P30 CA006516-46 (to G.P.), the
Human Frontier Science Program RGP0024 Grant (to A.A.K.), National
Health and Medical Research Council of Australia Grants 1026112 and
613686, and a public-private partnership between the Intramural Research
Programs of the National Human Genome Research Institute, the National
Cancer Institute, and Eli Lilly and Company coordinated by the
Foundation for the National Institutes of Health.
NR 35
TC 63
Z9 64
U1 0
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 AUG 13
PY 2013
VL 110
IS 33
BP 13481
EP 13486
DI 10.1073/pnas.1304227110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 200LA
UT WOS:000323069200063
PM 23901115
ER
PT J
AU Panigrahy, D
Kalish, BT
Huang, S
Bielenberg, DR
Le, HD
Yang, J
Edin, ML
Lee, CR
Benny, O
Mudge, DK
Butterfield, CE
Mammoto, A
Mammoto, T
Inceoglu, B
Jenkins, RL
Simpson, MA
Akino, T
Lih, FB
Tomer, KB
Ingber, DE
Hammock, BD
Falck, JR
Manthati, VL
Kaipainen, A
D'Amore, PA
Puder, M
Zeldin, DC
Kieran, MW
AF Panigrahy, Dipak
Kalish, Brian T.
Huang, Sui
Bielenberg, Diane R.
Le, Hau D.
Yang, Jun
Edin, Matthew L.
Lee, Craig R.
Benny, Ofra
Mudge, Dayna K.
Butterfield, Catherine E.
Mammoto, Akiko
Mammoto, Tadanori
Inceoglu, Bora
Jenkins, Roger L.
Simpson, Mary A.
Akino, Tomoshige
Lih, Fred B.
Tomer, Kenneth B.
Ingber, Donald E.
Hammock, Bruce D.
Falck, John R.
Manthati, Vijaya L.
Kaipainen, Arja
D'Amore, Patricia A.
Puder, Mark
Zeldin, Darryl C.
Kieran, Mark W.
TI Epoxyeicosanoids promote organ and tissue regeneration
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE autacoid; organ regeneration; small molecule mediator; angiocrine; VEGF
ID SOLUBLE EPOXIDE HYDROLASE; ENDOTHELIAL GROWTH-FACTOR;
EPOXYEICOSATRIENOIC ACIDS; LIVER-REGENERATION; ANGIOCRINE SIGNALS;
TUMOR-GROWTH; STEM-CELLS; IN-VIVO; ANGIOGENESIS; EXPRESSION
AB Epoxyeicosatrienoic acids (EETs), lipid mediators produced by cytochrome P450 epoxygenases, regulate inflammation, angiogenesis, and vascular tone. Despite pleiotropic effects on cells, the role of these epoxyeicosanoids in normal organ and tissue regeneration remains unknown. EETs are produced predominantly in the endothelium. Normal organ and tissue regeneration require an active paracrine role of the microvascular endothelium, which in turn depends on angiogenic growth factors. Thus, we hypothesize that endothelial cells stimulate organ and tissue regeneration via production of bioactive EETs. To determine whether endothelial-derived EETs affect physiologic tissue growth in vivo, we used genetic and pharmacological tools to manipulate endogenous EET levels. We show that endothelial-derived EETs play a critical role in accelerating tissue growth in vivo, including liver regeneration, kidney compensatory growth, lung compensatory growth, wound healing, corneal neovascularization, and retinal vascularization. Administration of synthetic EETs recapitulated these results, whereas lowering EET levels, either genetically or pharmacologically, delayed tissue regeneration, demonstrating that pharmacological modulation of EETs can affect normal organ and tissue growth. We also show that soluble epoxide hydrolase inhibitors, which elevate endogenous EET levels, promote liver and lung regeneration. Thus, our observations indicate a central role for EETs in organ and tissue regeneration and their contribution to tissue homeostasis.
C1 [Panigrahy, Dipak; Kalish, Brian T.; Bielenberg, Diane R.; Le, Hau D.; Benny, Ofra; Mudge, Dayna K.; Butterfield, Catherine E.; Mammoto, Akiko; Mammoto, Tadanori; Akino, Tomoshige; Ingber, Donald E.; Puder, Mark; Kieran, Mark W.] Harvard Univ, Sch Med, Boston Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA.
[Kalish, Brian T.; Le, Hau D.; Puder, Mark] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Surg, Boston, MA 02115 USA.
[Panigrahy, Dipak; Kieran, Mark W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA.
[Panigrahy, Dipak; Mudge, Dayna K.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Ctr Vasc Biol Res, Boston, MA 02115 USA.
[Panigrahy, Dipak; Mudge, Dayna K.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA.
[Le, Hau D.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02115 USA.
[Huang, Sui] Inst Syst Biol, Seattle, WA 98109 USA.
[Yang, Jun; Inceoglu, Bora; Hammock, Bruce D.] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA.
[Yang, Jun] Univ Calif Davis, Ctr Canc, Davis, CA 95616 USA.
[Edin, Matthew L.; Lih, Fred B.; Tomer, Kenneth B.; Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA.
[Lee, Craig R.] Univ N Carolina, Eshelman Sch Pharm, Div Pharmacotherapy & Expt Therapeut, Chapel Hill, NC 27599 USA.
[Jenkins, Roger L.; Simpson, Mary A.] Lahey Clin Med Ctr, Dept Transplantat, Burlington, MA 01805 USA.
[Ingber, Donald E.] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA.
[Falck, John R.; Manthati, Vijaya L.] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75235 USA.
[Kaipainen, Arja] Fred Hutchinson Canc Res Ctr, Clin Res Div, Seattle, WA 98109 USA.
[D'Amore, Patricia A.] Harvard Univ, Sch Med, Schepens Eye Res Inst, Dept Ophthalmol,Massachusetts Eye & Ear, Boston, MA 02114 USA.
RP Panigrahy, D (reprint author), Harvard Univ, Sch Med, Boston Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA.
EM dpanigra@bidmc.harvard.edu; bdhammock@ucdavis.edu; zeldin@niehs.nih.gov;
mark_kieran@dfci.harvard.edu
RI Yang, Jun/B-2262-2010;
OI Yang, Jun/0000-0002-4630-3838; Kieran, Mark/0000-0003-2184-7692; Falck,
John/0000-0002-9219-7845; Edin, Matthew/0000-0002-7042-500X; Lee,
Craig/0000-0003-3595-5301; Inceoglu, Bora/0000-0002-8473-6036
FU National Cancer Institute Grant [RO1CA148633-01A4]; Stop and Shop
Pediatric Brain Tumor Fund; C. J. Buckley Pediatric Brain Tumor Fund;
Joshua Ryan Rappaport Fellowship; Children's Hospital Boston Surgical
Foundation; Vascular Biology Program; Howard Hughes Medical Institute
Research Fellowship; Intramural Research Program of the National
Institutes of Health (NIH), National Institute of Environmental Health
Sciences (NIEHS) [Z01 025034, Z01 050167]; NIH [R01 GM088199, GM31278,
R01 ES002710, R01 ES013933, CA045548]; Robert A. Welch Foundation
[GL625910]; NIEHS Superfund Basic Research Program NIH [P42 ES004699]
FX We thank Kristin Johnson for photography and preparation of the figures;
J. Alyce Bradbury, Joan P. Graves, Laura M. DeGraff, and Ricky Sanchez
for excellent technical assistance; and Sung Hee Hwang for sEHi. This
work was supported by National Cancer Institute Grant RO1CA148633-01A4
(to D.P.); the Stop and Shop Pediatric Brain Tumor Fund (M.W.K.); the C.
J. Buckley Pediatric Brain Tumor Fund (M.W.K.); the Joshua Ryan
Rappaport Fellowship (H.D.L.); the Children's Hospital Boston Surgical
Foundation and the Vascular Biology Program (M.P. and H.D.L.); a Howard
Hughes Medical Institute Research Fellowship (to B.T.K.); Intramural
Research Program of the National Institutes of Health (NIH), National
Institute of Environmental Health Sciences (NIEHS) (Z01 025034 to
D.C.Z.; Z01 050167 to K.B.T.); NIH Grant R01 GM088199 (to C.R.L.); NIH
Grant GM31278 and Robert A. Welch Foundation Grant GL625910 (to J.R.F.);
NIEHS Superfund Basic Research Program NIH Grant P42 ES004699 and NIH
Grants R01 ES002710 and R01 ES013933 (to B.D.H.); and NIH Grant CA045548
(to D.E.I.). B.D.H. is a George and Judy Marcus Senior Fellow of the
American Asthma Foundation.
NR 47
TC 42
Z9 45
U1 2
U2 40
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 AUG 13
PY 2013
VL 110
IS 33
BP 13528
EP 13533
DI 10.1073/pnas.1311565110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 200LA
UT WOS:000323069200071
PM 23898174
ER
PT J
AU Chen, J
Feigenbaum, L
Awasthi, P
Butcher, DO
Anver, MR
Golubeva, YG
Bamford, R
Zhang, XJ
St Claire, MB
Thomas, CJ
Discepolo, V
Jabri, B
Waldmann, TA
AF Chen, Jing
Feigenbaum, Lionel
Awasthi, Parirokh
Butcher, Donna O.
Anver, Miriam R.
Golubeva, Yelena G.
Bamford, Richard
Zhang, Xiaojie
St Claire, Mark B.
Thomas, Craig J.
Discepolo, Valentina
Jabri, Bana
Waldmann, Thomas A.
TI Insulin-dependent diabetes induced by pancreatic beta cell expression of
IL-15 and IL-15R alpha
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID NATURAL-KILLER-CELL; CD8 T-CELLS; ENTEROVIRUS INFECTION; TRANS
PRESENTATION; CUTTING EDGE; RECENT-ONSET; IN-VIVO; TYPE-1; MELLITUS;
ISLETS
AB Increased serum levels of IL-15 are reported in type 1 diabetes (T1D). Here we report elevated serum soluble IL-15R alpha levels in human T1D. To investigate the role of IL-15/IL-15R alpha in the pathogenesis of T1D, we generated double transgenic mice with pancreatic beta-cell expression of IL-15 and IL-15R alpha. The mice developed hyperglycemia, marked mononuclear cell infiltration, beta-cell destruction, and anti-insulin autoantibodies that mimic early human T1D. The diabetes in this model was reversed by inhibiting IL-15 signaling with anti-IL2/IL15R beta (anti-CD122), which blocks IL-15 transpresentation. Furthermore, the diabetes could be reversed by administration of the Janus kinase 2/3 inhibitor tofacitinib, which blocks IL-15 signaling. In an alternative diabetes model, nonobese diabetic mice, IL15/IL-15R alpha expression was increased in islet cells in the prediabetic stage, and inhibition of IL-15 signaling with anti-CD122 at the prediabetic stage delayed diabetes development. In support of the view that these observations reflect the conditions in humans, we demonstrated pancreatic islet expression of both IL-15 and IL-15R alpha in human T1D. Taken together our data suggest that disordered IL-15 and IL-15R alpha may be involved in T1D pathogenesis and the IL-15/IL15R alpha system and its signaling pathway may be rational therapeutic targets for early T1D.
C1 [Chen, Jing; Waldmann, Thomas A.] NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Feigenbaum, Lionel; Awasthi, Parirokh; Butcher, Donna O.; Anver, Miriam R.; Golubeva, Yelena G.] NCI, Lab Anim Sci Program, SAIC Frederick Inc, Frederick Natl Lab Canc Res, Ft Detrick, MD 21702 USA.
[Bamford, Richard] Transponics, Jacobus, PA 17407 USA.
[Zhang, Xiaojie; St Claire, Mark B.] NIDDK, Lab Anim Sci Sect, Bethesda, MD 20892 USA.
[Thomas, Craig J.] NHGRI, NIH, Chem Genom Ctr, Rockville, MD 20850 USA.
[Discepolo, Valentina; Jabri, Bana] Univ Chicago, Dept Pediat, Chicago, IL 60637 USA.
[Discepolo, Valentina] Univ Naples Federico II, Dept Pediat, I-80131 Naples, Italy.
RP Waldmann, TA (reprint author), NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
EM tawald@helix.nih.gov
FU intramural research program of the Center for Cancer Research, National
Cancer Institute (NCI), National Institutes of Health (NIH); federal
funds from NCI, NIH [HHSN261200800001E]
FX We thank Dr. Oksana Gavrilova (National Institute of Diabetes and
Digestive and Kidney Diseases) for the technical support of islet
isolation and Dr. Jun-Li Liu (McGill University) for kindly providing us
the rat insulin promoter construct. This work was supported by the
intramural research program of the Center for Cancer Research, National
Cancer Institute (NCI), National Institutes of Health (NIH) and in part
by federal funds from NCI, NIH, under Contract HHSN261200800001E.
NR 39
TC 19
Z9 19
U1 0
U2 11
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 AUG 13
PY 2013
VL 110
IS 33
BP 13534
EP 13539
DI 10.1073/pnas.1312911110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 200LA
UT WOS:000323069200072
PM 23904478
ER
PT J
AU Manoli, I
Sysol, JR
Li, LL
Houillier, P
Garone, C
Wang, C
Zerfas, PM
Cusmano-Ozog, K
Young, S
Trivedi, NS
Cheng, J
Sloan, JL
Chandler, RJ
Abu-Asab, M
Tsokos, M
Elkahloun, AG
Rosen, S
Enns, GM
Berry, GT
Hoffmann, V
DiMauro, S
Schnermann, J
Venditti, CP
AF Manoli, Irini
Sysol, Justin R.
Li, Lingli
Houillier, Pascal
Garone, Caterina
Wang, Cindy
Zerfas, Patricia M.
Cusmano-Ozog, Kristina
Young, Sarah
Trivedi, Niraj S.
Cheng, Jun
Sloan, Jennifer L.
Chandler, Randy J.
Abu-Asab, Mones
Tsokos, Maria
Elkahloun, Abdel G.
Rosen, Seymour
Enns, Gregory M.
Berry, Gerard T.
Hoffmann, Victoria
DiMauro, Salvatore
Schnermann, Jurgen
Venditti, Charles P.
TI Targeting proximal tubule mitochondrial dysfunction attenuates the renal
disease of methylmalonic acidemia
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE cobalamin; chronic renal failure; megamitochondria; organic acidemia
ID GENE DELIVERY RESCUES; NEUTROPHIL GELATINASE; MOUSE MODEL; MICE;
ACIDOSIS; EXCRETION; LIPOCALIN; BIOMARKER; ACIDURIA; HUMANS
AB Isolated methylmalonic acidemia (MMA), caused by deficiency of the mitochondrial enzyme methylmalonyl-CoA mutase (MUT), is often complicated by end stage renal disease that is resistant to conventional therapies, including liver transplantation. To establish a viable model of MMA renal disease, Mut was expressed in the liver of Mut(-/-) mice as a stable transgene under the control of an albumin (INS-Alb-Mut) promoter. Mut(-/-);Tg(INS-Alb-Mut) mice, although completely rescued from neonatal lethality that was displayed by Mut(-/-) mice, manifested a decreased glomerular filtration rate (GFR), chronic tubulointerstitial nephritis and ultrastructural changes in the proximal tubule mitochondria associated with aberrant tubular function, as demonstrated by single-nephron GFR studies. Microarray analysis of Mut(-/-);Tg(INS-Alb-Mut) kidneys identified numerous biomarkers, including lipocalin-2, which was then used to monitor the response of the GFR to antioxidant therapy in the mouse model. Renal biopsies and biomarker analysis from a large and diverse patient cohort (ClinicalTrials.gov identifier: NCT00078078) precisely replicated the findings in the animals, establishing Mut(-/-);Tg(INS-Alb-Mut) mice as a unique model of MMA renal disease. Our studies suggest proximal tubular mitochondrial dysfunction is a key pathogenic mechanism of MMA-associated kidney disease, identify lipocalin-2 as a biomarker of increased oxidative stress in the renal tubule, and demonstrate that antioxidants can attenuate the renal disease of MMA.
C1 [Manoli, Irini; Sysol, Justin R.; Wang, Cindy; Sloan, Jennifer L.; Chandler, Randy J.; Venditti, Charles P.] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
[Li, Lingli; Houillier, Pascal; Schnermann, Jurgen] NIDDK, Kidney Dis Branch, Bethesda, MD 20814 USA.
[Houillier, Pascal] Paris Descartes Univ, INSERM, Georges Pompidou European Hosp, AP HP,Unite Mixte Rech S 872,Dept Physiol, F-75015 Paris, France.
[Garone, Caterina; DiMauro, Salvatore] Columbia Univ, Med Ctr, Coll Phys & Surg, New York, NY 10032 USA.
[Garone, Caterina] Univ Bologna & Turin, Human Genet Joint PhD Program, I-10126 Turin, Italy.
[Zerfas, Patricia M.; Hoffmann, Victoria] NIH, Off Res Serv, Div Vet Resources, Bethesda, MD 20892 USA.
[Cusmano-Ozog, Kristina; Enns, Gregory M.] Stanford Univ, Div Med Genet, Stanford, CA 94305 USA.
[Young, Sarah] Duke Univ, Med Ctr, Div Med Genet, Biochem Genet Lab, Durham, NC 27713 USA.
[Trivedi, Niraj S.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
[Cheng, Jun] NHGRI, Embryon Stem Cell & Transgen Mouse Core Facil, NIH, Bethesda, MD 20892 USA.
[Abu-Asab, Mones; Tsokos, Maria] NIH, Ultrastruct Pathol Sect, Ctr Canc Res, Bethesda, MD 20892 USA.
[Elkahloun, Abdel G.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
[Rosen, Seymour] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA.
[Rosen, Seymour] Boston Childrens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Berry, Gerard T.] Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA 02115 USA.
RP Venditti, CP (reprint author), NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
EM venditti@mail.nih.gov
OI Garone, Caterina/0000-0003-4928-1037; Berry, Gerard/0000-0001-5299-3313;
Abu-Asab, Mones/0000-0002-4047-1232; Manoli, Irini/0000-0003-1543-2941
FU Intramural Research Program of the National Human Genome Research
Institute; National Institute of Diabetes and Digestive and Kidney
Diseases; National Cancer Institute; Office of the Director of the
National Institutes of Health; Angels; Philippe Foundation; Oak Ridge
Institute for Science and Education; Paris Descartes University, France
FX We thank all patients and their families; Shelley Hoogstraten-Miller for
veterinary support; Irene Ginty, Cherry Yang, Tina Aroyo, Theresa
Ferrine, and Lemlem Alemu for mouse maintenance; and Isa Bernardini and
Roxanne Fischer for processing patient samples. This work was supported
by the Intramural Research Program of the National Human Genome Research
Institute (I.M., J.R.S., C.W., N.S.T., J.C., J.L.S., R.J.C., A.G.E., and
C.P.V.), the National Institute of Diabetes and Digestive and Kidney
Diseases (L.L., P.H., and J.S.), the National Cancer Institute (M.A.-A.
and M.T.), and the Office of the Director (P.M.Z. and V.H.) of the
National Institutes of Health. J.R.S. and C.W. were also supported by
the Angels for Alyssa (MMA Research Fund). P.H. was supported by the
Philippe Foundation, the Oak Ridge Institute for Science and Education,
and Paris Descartes University, France.
NR 31
TC 23
Z9 25
U1 1
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 AUG 13
PY 2013
VL 110
IS 33
BP 13552
EP 13557
DI 10.1073/pnas.1302764110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 200LA
UT WOS:000323069200075
PM 23898205
ER
PT J
AU Johnson, TP
Patel, K
Johnson, KR
Maric, D
Calabresi, PA
Hasbun, R
Nath, A
AF Johnson, Tory P.
Patel, Karan
Johnson, Kory R.
Maric, Dragan
Calabresi, Peter A.
Hasbun, Rodrigo
Nath, Avindra
TI Induction of IL-17 and nonclassical T-cell activation by HIV-Tat
proteinj
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE CNS inflammation; chronic inflammation; lymphocyte; central nervous
system; chromatin
ID RECONSTITUTION INFLAMMATORY SYNDROME; ENDOTHELIAL GROWTH-FACTOR;
ANTIRETROVIRAL THERAPY; IMMUNE ACTIVATION; IN-VIVO; INFECTION;
TRANSACTIVATION; RECEPTOR; INTERLEUKIN-8; ACETYLATION
AB Chronic immune activation is a major complication of antiretroviral therapy (ART) for HIV infection and can cause a devastating immune reconstitution inflammatory syndrome (IRIS) in the brain. The mechanism of T-cell activation in this population is not well understood. We found HIV-Tat protein and IL-17-expressing mononuclear cells in the brain of an individual with IRIS. Tat was also present in the CSF of individuals virologically controlled on ART. Hence we examined if Tat protein could directly activate T cells. Tat transcriptionally dysregulated 94 genes and induced secretion of 11 cytokines particularly activation of IL-17 signaling pathways supporting the development of a proinflammatory state. Tat increased IL-17 transcription and secretion in T cells. Tat entered the T cells rapidly by clathrin-mediated endocytosis and localized to both the cytoplasm and the nucleus. Tat activated T cells through a nonclassical pathway dependent upon vascular endothelial growth factor receptor-2 and downstream secondary signaling pathways but independent of the T-cell receptor. However, Tat stimulation of T cells did not induce T-cell proliferation but increased viral infectivity. This study demonstrates Tat's role as a virulence factor, by driving T-cell activation and contributing to IRIS pathophysiology. This supports the necessity of an anti-Tat therapy in conjunction with ART and identifies multiple targetable pathways to prevent Tat-mediated T-cell activation.
C1 [Johnson, Tory P.; Patel, Karan; Johnson, Kory R.; Maric, Dragan; Nath, Avindra] NINDS, Sect Infect Nervous Syst, NIH, Bethesda, MD 20892 USA.
[Calabresi, Peter A.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21287 USA.
[Hasbun, Rodrigo] Univ Texas Hlth Sci Ctr Houston, Dept Internal Med, Houston, TX 77030 USA.
RP Nath, A (reprint author), NINDS, Sect Infect Nervous Syst, NIH, Bethesda, MD 20892 USA.
EM natha@ninds.nih.gov
FU National Institutes of Health [R01NS039253, R01NS056884, F31NS063855];
intramural National Institute of Neurological Disorders and Stroke funds
FX We thank Richa Tyagi, Lee Blosser, Caroline Anderson, Lena Hu, and Abdel
Elkahloun for technical assistance; Abhik Ray-Chaudhury for
interpretation of histopathological findings; Scott Letendre for
providing CSF samples; and Pablo Okhuysen for requesting brain biopsy
specimen. We thank Michael C. Haffner for assistance in manuscript
preparation and useful discussions. This work was supported by National
Institutes of Health Grants R01NS039253, R01NS056884, and F31NS063855
and intramural National Institute of Neurological Disorders and Stroke
funds.
NR 40
TC 64
Z9 64
U1 0
U2 5
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD AUG 13
PY 2013
VL 110
IS 33
BP 13588
EP 13593
DI 10.1073/pnas.1308673110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 200LA
UT WOS:000323069200081
PM 23898208
ER
PT J
AU Tomasi, D
Wang, GJ
Volkow, ND
AF Tomasi, Dardo
Wang, Gene-Jack
Volkow, Nora D.
TI Energetic cost of brain functional connectivity
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE fMRI connectivity; PET-FDG; allometric scaling; energy budget; graph
theory
ID SMALL-WORLD; ALZHEIMERS-DISEASE; CORTICAL HUBS; LOW-FREQUENCY; NETWORKS;
MRI; FLUCTUATIONS; ORGANIZATION; DYNAMICS; IMAGES
AB The brain's functional connectivity is complex, has high energetic cost, and requires efficient use of glucose, the brain's main energy source. It has been proposed that regions with a high degree of functional connectivity are energy efficient and can minimize consumption of glucose. However, the relationship between functional connectivity and energy consumption in the brain is poorly understood. To address this neglect, here we propose a simple model for the energy demands of brain functional connectivity, which we tested with positron emission tomography and MRI in 54 healthy volunteers at rest. Higher glucose metabolism was associated with proportionally larger MRI signal amplitudes, and a higher degree of connectivity was associated with nonlinear increases in metabolism, supporting our hypothesis for the energy efficiency of the connectivity hubs. Basal metabolism (in the absence of connectivity) accounted for 30% of brain glucose utilization, which suggests that the spontaneous brain activity accounts for 70% of the energy consumed by the brain. The energy efficiency of the connectivity hubs was higher for ventral precuneus, cerebellum, and subcortical hubs than for cortical hubs. The higher energy demands of brain communication that hinges upon higher connectivity could render brain hubs more vulnerable to deficits in energy delivery or utilization and help explain their sensitivity to neurodegenerative conditions, such as Alzheimer's disease.
C1 [Tomasi, Dardo; Volkow, Nora D.] NIAAA, Bethesda, MD 20892 USA.
[Wang, Gene-Jack] Brookhaven Natl Lab, Dept Biosci, Upton, NY 11973 USA.
[Wang, Gene-Jack] SUNY Stony Brook, Dept Radiol, Stony Brook, NY 11794 USA.
[Volkow, Nora D.] Natl Inst Drug Abuse, Bethesda, MD 20892 USA.
RP Tomasi, D (reprint author), NIAAA, Bethesda, MD 20892 USA.
EM tomasidg@mail.nih.gov
RI Tomasi, Dardo/J-2127-2015
FU National Institutes of Alcohol Abuse and Alcoholism [2R01AA09481];
National Center for Research Resources [GCRC 5-M01-RR-10710]
FX We thank Ruben Baler, Ruiliang Wang, David Alexoff, Christopher Wong,
Millard Jayne, Paul Vaska, David Schlyer, Karen Apelskog-Torres, Barbara
Hubbard, and Joanna S. Fowler for assistance in various aspects of these
studies. This work was accomplished with support from National
Institutes of Alcohol Abuse and Alcoholism Grant 2R01AA09481 and
National Center for Research Resources Grant GCRC 5-M01-RR-10710.
NR 44
TC 92
Z9 95
U1 1
U2 26
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 AUG 13
PY 2013
VL 110
IS 33
BP 13642
EP 13647
DI 10.1073/pnas.1303346110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 200LA
UT WOS:000323069200090
PM 23898179
ER
PT J
AU Mazouzi, A
Vigouroux, A
Aikeshev, B
Brooks, PJ
Saparbaev, MK
Morera, S
Ishchenko, AA
AF Mazouzi, Abdelghani
Vigouroux, Armelle
Aikeshev, Bulat
Brooks, Philip J.
Saparbaev, Murat K.
Morera, Solange
Ishchenko, Alexander A.
TI Insight into mechanisms of 3 '-5 ' exonuclease activity and removal of
bulky 8,5 '-cyclopurine adducts by apurinic/apyrimidinic endonucleases
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE oxidative DNA damage; endonuclease IV; DNA glycosylase; base excision
repair; damage specific endonuclease
ID INCISION REPAIR PATHWAY; NUCLEOTIDE EXCISION-REPAIR; SINGLE-STRAND
BREAKS; OXIDATIVE DNA-DAMAGE; ESCHERICHIA-COLI; HUMAN-CELLS;
SACCHAROMYCES-CEREVISIAE; MAMMALIAN-CELLS; APE1; LESIONS
AB 8,5'-cyclo-2'-deoxyadenosine (cdA) and 8,5'-cyclo-2'-deoxyguanosine generated in DNA by both endogenous oxidative stress and ionizing radiation are helix-distorting lesions and strong blocks for DNA replication and transcription. In duplex DNA, these lesions are repaired in the nucleotide excision repair (NER) pathway. However, lesions at DNA strand breaks are most likely poor substrates for NER. Here we report that the apurinic/apyrimidinic (AP) endonucleases-Escherichia coli Xth and human APE1-can remove 5'S cdA (S-cdA) at 3' termini of duplex DNA. In contrast, E. coli Nfo and yeast Apn1 are unable to carry out this reaction. None of these enzymes can remove S-cdA adduct located at 1 or more nt away from the 3' end. To understand the structural basis of 3' repair activity, we determined a high-resolution crystal structure of E. coli Nfo-H69A mutant bound to a duplex DNA containing an alpha-anomeric 2'-deoxyadenosine: T base pair. Surprisingly, the structure reveals a bound nucleotide incision repair (NIR) product with an abortive 3'-terminal dC close to the scissile position in the enzyme active site, providing insight into the mechanism for Nfo-catalyzed 3'-> 5' exonuclease function and its inhibition by 3'-terminal S-cdA residue. This structure was used as a template to model 3'-terminal residues in the APE1 active site and to explain biochemical data on APE1-catalyzed 3' repair activities. We propose that Xth and APE1 may act as a complementary repair pathway to NER to remove S-cdA adducts from 3' DNA termini in E. coli and human cells, respectively.
C1 [Mazouzi, Abdelghani; Aikeshev, Bulat; Saparbaev, Murat K.; Ishchenko, Alexander A.] Univ Paris 11, Lab Stabilite Genet & Oncogenese, Inst Cancerol Gustave Roussy, CNRS,Unite Mixte Rech 8200, F-94805 Villejuif, France.
[Vigouroux, Armelle; Morera, Solange] CNRS, Lab Enzymol & Biochim Struct, F-91198 Gif Sur Yvette, France.
[Aikeshev, Bulat] LN Gumilev Eurasian Natl Univ, Astana 010008, Kazakhstan.
[Brooks, Philip J.] NIAAA, Lab Neurogenet, Bethesda, MD 20892 USA.
[Brooks, Philip J.] NIAAA, Div Metab & Hlth Effects, Bethesda, MD 20892 USA.
[Brooks, Philip J.] NIH, Off Rare Dis Res, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
RP Morera, S (reprint author), CNRS, Lab Enzymol & Biochim Struct, F-91198 Gif Sur Yvette, France.
EM morera@lebs.cnrs-gif.fr; ichtchen@igr.fr
RI Ishchenko, Alexander/D-4133-2013; Saparbaev, Murat/N-3225-2015
OI Saparbaev, Murat/0000-0002-4630-1074
FU Fondation de France [2012 00029161]; Russian Federal Program "Scientific
and education personnel for innovative Russia" [8473]; Centre National
de la Recherche Scientifique funds [PICS N5479-Russie]; Agence Nationale
pour la Recherche Blanc [ANR-09-GENO-000]; Electricite de France Contrat
Radioprotection; Institut de Cancerologie Gustave-Roussy; Bolashak
International Program, Kazakhstan; Agence Nationale pour la Recherche
FX We thank Dr. Jacques Laval for critical reading of the manuscript and
thoughtful discussions, and Dr. Beatriz Guimaraes for help in data
collection on PROXIMA I at SOLEIL. This work was supported by Fondation
de France Grant 2012 00029161 (to A.A.I.) (www.fondationdefrance.org);
Russian Federal Program "Scientific and education personnel for
innovative Russia" for 2009-2013 No. 8473 (to A.A.I.) (www.fcpk.ru);
Centre National de la Recherche Scientifique funds to S.M. and Grant
PICS N5479-Russie (to M.K.S.) (www.cnrs.fr); Agence Nationale pour la
Recherche Blanc 2010 Projet ANR-09-GENO-000 (to M.K.S.)
(www.agence-nationale-recherche.fr); and Electricite de France Contrat
Radioprotection RB 2012 (to M.K.S.) (www.edf.fr). The crystallization
work has benefited from the Laboratoire d'Enzymologie et Biochimie
Structurales (LEBS) facilities of the IMAGIF Structural Biology and
Proteomic Unit in the "Centre de Recherche de Gif" (www.imagif.cnrs.fr).
A.M. and B.A. were supported by the student scholarships from Institut
de Cancerologie Gustave-Roussy (www.igr.fr) and the Bolashak
International Program, Kazakhstan (www.bolashak.gov.kz), respectively.
Funding for open access charge was provided by Agence Nationale pour la
Recherche.
NR 46
TC 17
Z9 17
U1 0
U2 19
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD AUG 13
PY 2013
VL 110
IS 33
BP E3071
EP E3080
DI 10.1073/pnas.1305281110
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 200LA
UT WOS:000323069200009
PM 23898172
ER
PT J
AU Espeland, MA
Shumaker, SA
Leng, I
Manson, JE
Brown, CM
LeBlanc, ES
Vaughan, L
Robinson, J
Rapp, SR
Goveas, JS
Lane, D
Wactawski-Wende, J
Stefanick, ML
Li, WJ
Resnick, SM
AF Espeland, Mark A.
Shumaker, Sally A.
Leng, Iris
Manson, JoAnn E.
Brown, Candice M.
LeBlanc, Erin S.
Vaughan, Leslie
Robinson, Jennifer
Rapp, Stephen R.
Goveas, Joseph S.
Lane, Dorothy
Wactawski-Wende, Jean
Stefanick, Marcia L.
Li, Wenjun
Resnick, Susan M.
CA WHIMSY Study Grp
TI Long-Term Effects on Cognitive Function of Postmenopausal Hormone
Therapy Prescribed to Women Aged 50 to 55 Years
SO JAMA INTERNAL MEDICINE
LA English
DT Article
ID HEALTH INITIATIVE MEMORY; CONJUGATED EQUINE ESTROGENS; RANDOMIZED
CONTROLLED-TRIAL; ALZHEIMERS-DISEASE; BRAIN VOLUMES; DEMENTIA;
IMPAIRMENT; REPLACEMENT; MENOPAUSE; WHIMS
AB IMPORTANCE Postmenopausal hormone therapy with conjugated equine estrogens (CEEs) may adversely affect older women's cognitive function. It is not known whether this extends to younger women.
OBJECTIVE To test whether prescribing CEE-based hormone therapy to postmenopausal women aged 50 to 55 years has longer-term effects on cognitive function.
DESIGN Trained, masked staff assessed participants with an annual telephone-administered cognitive battery that included measures of global and domain-specific cognitive functions. Cognitive testing was conducted an average of 7.2 years after the trials ended, when women had a mean age of 67.2 years, and repeated 1 year later. Enrollment occurred from 1996 through 1999.
SETTING Forty academic research centers.
PARTICIPANTS The study population comprised 1326 postmenopausal women, who had begun treatment in 2 randomized placebo-controlled clinical trials of hormone therapy when aged 50 to 55 years.
INTERVENTION The clinical trials in which the women had participated had compared 0.625 mg CEE with or without 2.5 mg medroxyprogesterone acetate over a mean of 7.0 years.
MAIN OUTCOMES AND MEASURES The primary outcome was global cognitive function. Secondary outcomes were verbal memory, attention, executive function, verbal fluency, and working memory.
RESULTS Global cognitive function scores from women who had been assigned to CEE-based therapies were similar to those from women assigned to placebo: mean (95% CI) intervention effect of 0.02 (-0.08 to 0.12) standard deviation units (P = .66). Similarly, no overall differences were found for any individual cognitive domain (all P > .15). Prespecified subgroup analyses found some evidence that CEE-based therapies may have adversely affected verbal fluency among women who had prior hysterectomy or prior use of hormone therapy: mean treatment effects of -0.17 (-0.33 to -0.02) and -0.25 (-0.42 to -0.08), respectively; however, this may be a chance finding.
CONCLUSIONS AND RELEVANCE CEE-based therapies produced no overall sustained benefit or risk to cognitive function when administered to postmenopausal women aged 50 to 55 years. We are not able to address whether initiating hormone therapy during menopause and maintaining therapy until any symptoms are passed affects cognitive function, either in the short or longer term.
C1 [Espeland, Mark A.; Leng, Iris] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC 27157 USA.
[Shumaker, Sally A.; Vaughan, Leslie] Wake Forest Sch Med, Dept Social Sci & Hlth Policy, Winston Salem, NC 27157 USA.
[Manson, JoAnn E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med,Dept Epidemiol, Boston, MA 02115 USA.
[Brown, Candice M.] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC 27157 USA.
[LeBlanc, Erin S.] Kaiser Permanente Northwest, Ctr Hlth Res, Portland, OR USA.
[Robinson, Jennifer] Univ Iowa, Dept Epidemiol, Div Cardiol, Iowa City, IA USA.
[Robinson, Jennifer] Univ Iowa, Dept Med, Div Cardiol, Iowa City, IA 52242 USA.
[Rapp, Stephen R.] Wake Forest Sch Med, Dept Psychiat & Behav Med, Winston Salem, NC 27157 USA.
[Goveas, Joseph S.] Med Coll Wisconsin, Dept Psychiat & Behav Med, Milwaukee, WI 53226 USA.
[Lane, Dorothy] SUNY Stony Brook, Dept Prevent Med, Stony Brook, NY 11794 USA.
[Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA.
[Stefanick, Marcia L.] Stanford Univ, Dept Med, Prevent Res Ctr, Palo Alto, CA 94304 USA.
[Li, Wenjun] Univ Massachusetts, Sch Med, Div Prevent & Behav Med, Worcester, MA USA.
[Resnick, Susan M.] NIA, Lab Behav Neurosci, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Espeland, MA (reprint author), Wake Forest Sch Med, Dept Biostat Sci, Med Ctr Blvd, Winston Salem, NC 27157 USA.
EM mespelan@wakehealth.edu
RI Li, Wenjun/F-5634-2015
OI Li, Wenjun/0000-0001-5335-7386
FU National Institute on Aging [HHSN-271-2011-00004C]; National Heart,
Lung, and Blood Institute, US Department of Health and Human Services
FX This study was supported by the National Institute on Aging, Contract
No. HHSN-271-2011-00004C. WHIMSY is funded by the National Institute on
Aging, Contract No. HHSN-271-2011-00004C, and the WHI program is funded
by the National Heart, Lung, and Blood Institute, US Department of
Health and Human Services.
NR 35
TC 38
Z9 39
U1 0
U2 10
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 2168-6106
J9 JAMA INTERN MED
JI JAMA Intern. Med.
PD AUG 12
PY 2013
VL 173
IS 15
BP 1429
EP 1436
DI 10.1001/jamainternmed.2013.7727
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 218NY
UT WOS:000324440400008
PM 23797469
ER
PT J
AU Cadet, JL
Jayanthi, S
McCoy, MT
Ladenheim, B
St-Preux, F
Lehrmann, E
De, S
Becker, KG
Brannock, C
AF Cadet, Jean Lud
Jayanthi, Subramaniam
McCoy, Michael T.
Ladenheim, Bruce
St-Preux, Fabienne
Lehrmann, Elin
De, Supriyo
Becker, Kevin G.
Brannock, Christie
TI Genome-wide profiling identifies a subset of methamphetamine
(METH)-induced genes associated with METH-induced increased H4K5Ac
binding in the rat striatum
SO BMC GENOMICS
LA English
DT Article
DE ChIP sequencing; Neural networks; Epigenetics; Histone acetylation;
Microarray
ID TRANSCRIPTION FACTOR-BINDING; IMMEDIATE-EARLY GENES; HISTONE
ACETYLATION; SYNAPTIC PLASTICITY; NEUROPEPTIDE-B; C-FOS;
CHROMATIN-STRUCTURE; MESOLIMBIC SYSTEM; CAUDATE DOPAMINE; CHRONIC
COCAINE
AB Background: METH is an illicit drug of abuse that influences gene expression in the rat striatum. Histone modifications regulate gene transcription.
Methods: We therefore used microarray analysis and genome-scale approaches to examine potential relationships between the effects of METH on gene expression and on DNA binding of histone H4 acetylated at lysine 4 (H4K5Ac) in the rat dorsal striatum of METH-naive and METH-pretreated rats.
Results: Acute and chronic METH administration caused differential changes in striatal gene expression. METH also increased H4K5Ac binding around the transcriptional start sites (TSSs) of genes in the rat striatum. In order to relate gene expression to histone acetylation, we binned genes of similar expression into groups of 100 genes and proceeded to relate gene expression to H4K5Ac binding. We found a positive correlation between gene expression and H4K5Ac binding in the striatum of control rats. Similar correlations were observed in METH-treated rats. Genes that showed acute METH-induced increased expression in saline-pretreated rats also showed METH-induced increased H4K5Ac binding. The acute METH injection caused similar increases in H4K5Ac binding in METH-pretreated rats, without affecting gene expression to the same degree. Finally, genes that showed METH-induced decreased expression exhibited either decreases or no changes in H4K5Ac binding.
Conclusion: Acute METH injections caused increased gene expression of genes that showed increased H4K5Ac binding near their transcription start sites.
C1 [Cadet, Jean Lud; Jayanthi, Subramaniam; McCoy, Michael T.; Ladenheim, Bruce; St-Preux, Fabienne; Brannock, Christie] NIDA, Mol Neuropsychiat Res Branch, DHHS, NIH,Intramural Res Program, Baltimore, MD 21224 USA.
[Lehrmann, Elin; De, Supriyo; Becker, Kevin G.] NIA, Gene Express & Genom Unit, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Cadet, JL (reprint author), NIDA, Mol Neuropsychiat Res Branch, DHHS, NIH,Intramural Res Program, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM jcadet@intra.nida.nih.gov
OI Lehrmann, Elin/0000-0002-9869-9475; De, Supriyo/0000-0002-2075-7655;
Becker, Kevin/0000-0002-6794-6656
FU Intramural Research Program of the DHHS/NIH/NIDA; DHHS/NIH/NIA
FX This work was supported by funds of the Intramural Research Program of
the DHHS/NIH/NIDA and DHHS/NIH/NIA.
NR 98
TC 13
Z9 13
U1 0
U2 6
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 AUG 12
PY 2013
VL 14
AR 545
DI 10.1186/1471-2164-14-545
PG 19
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 202YE
UT WOS:000323256200001
PM 23937714
ER
PT J
AU Gremel, CM
Costa, RM
AF Gremel, Christina M.
Costa, Rui M.
TI Premotor cortex is critical for goal-directed actions
SO FRONTIERS IN COMPUTATIONAL NEUROSCIENCE
LA English
DT Article
DE premotor cortex; goal-directed actions; habitual actions; value-based
decision making; action selection
ID SUPPLEMENTARY MOTOR AREA; MEDIAL PREFRONTAL CORTEX; REINFORCER
DEVALUATION; NEURONAL-ACTIVITY; ACTION SELECTION; HABIT FORMATION;
FRONTAL-CORTEX; STRIATUM; PROJECTIONS; RATS
AB Shifting between motor plans is often necessary for adaptive behavior. When faced with changing consequences of one's actions, it is often imperative to switch from automatic actions to deliberative and controlled actions. The pre-supplementary motor area (pre-SMA) in primates, akin to the premotor cortex (M2) in mice, has been implicated in motor learning and planning, and action switching. We hypothesized that M2 would be differentially involved in goal-directed actions, which are controlled by their consequences vs. habits, which are more dependent on their past reinforcement history and less on their consequences. To investigate this, we performed M2 lesions in mice and then concurrently trained them to press the same lever for the same food reward using tow different schedules of reinforcement that differentially bias towards the use of goal-directed versus habitual action strategies. We then probed whether actions were dependent on their M2 lesions did not affect the acquisition of lever-pressing. However, in mice with M2 lesions, lever-pressing was insensitive to changes in expected outcome value following goal-directed training. However, habitual actions were intact. We confirmed a role for M2 in goal-directed but not habitual actions in separate groups of mice trained on the individual schedules biasing towards goal-directed versus habitual actions. These data indicate that M2 is critical for actions to be updated based on their consequences, and suggest that habitual action strategies may not require processing by M2 and the updating of motor plans.
C1 [Gremel, Christina M.; Costa, Rui M.] NIAAA, Lab Integrat Neurosci, NIH, Bethesda, MD 90034 USA.
[Costa, Rui M.] Champalimaud Inst Unknown, Champalimaud Neurosci Programme, Lisbon, Portugal.
RP Costa, RM (reprint author), Champalimaud Fdn, Champalimaud Neurosci Programme, Champalimaud Inst Unknown, Av De Brasilia, P-1400038 Lisbon, Portugal.
EM rui.costa@neuro.fchampalimaud.org
OI Costa, Rui/0000-0003-0495-8374
FU NIAAA Division of Intramural Clinical and Biological Research; European
Research Council [243393]; HHMI International Early Career Scientist
Grant
FX Christina M. Gremel performed the experiments and analyzed the data.
Christina M. Gremel and Rui M. Costa designed the experiments, and wrote
the paper. This work was supported by NIAAA Division of Intramural
Clinical and Biological Research, and European Research Council Grant
(243393) and HHMI International Early Career Scientist Grant to Rui M.
Costa.
NR 40
TC 11
Z9 11
U1 3
U2 23
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1662-5188
J9 FRONT COMPUT NEUROSC
JI Front. Comput. Neurosci.
PD AUG 12
PY 2013
VL 7
AR UNSP 110
DI 10.3389/fncom.2013.00110
PG 8
WC Mathematical & Computational Biology; Neurosciences
SC Mathematical & Computational Biology; Neurosciences & Neurology
GA 205BV
UT WOS:000323416600001
PM 23964233
ER
PT J
AU Luo, HT
Sun, SL
Li, P
Bu, DC
Cao, HM
Zhao, Y
AF Luo, Haitao
Sun, Silong
Li, Ping
Bu, Dechao
Cao, Haiming
Zhao, Yi
TI Comprehensive Characterization of 10,571 Mouse Large Intergenic
Noncoding RNAs from Whole Transcriptome Sequencing
SO PLOS ONE
LA English
DT Article
ID HUMAN GENOME; HUMAN-CELLS; REVEALS; ANNOTATION; SEQ; EXPRESSION;
DIFFERENTIATION; QUANTIFICATION; IDENTIFICATION; LANDSCAPE
AB Large intergenic noncoding RNAs (lincRNAs) have been recognized in recent years to constitute a significant portion of the mammalian transcriptome, yet their biological functions remain largely elusive. This is partly due to an incomplete annotation of tissue-specific lincRNAs in essential model organisms, particularly in mice, which has hindered the genetic annotation and functional characterization of these novel transcripts. In this report, we performed ab initio assembly of 1.9 billion tissue-specific RNA-sequencing reads across six tissue types, and identified 3,965 novel expressed lincRNAs in mice. Combining these with 6,606 documented lincRNAs, we established a comprehensive catalog of 10,571 transcribed lincRNAs. We then systemically analyzed all mouse lincRNAs to reveal that some of them are evolutionally conserved and that they exhibit striking tissue-specific expression patterns. We also discovered that mouse lincRNAs carry unique genomic signatures, and that their expression level is correlated with that of neighboring protein-coding transcripts. Finally, we predicted that a large portion of tissue-specific lincRNAs are functionally associated with essential biological processes including the cell cycle and cell development, and that they could play a key role in regulating tissue development and functionality. Our analyses provide a framework for continued discovery and annotation of tissue-specific lincRNAs in model organisms, and our transcribed mouse lincRNA catalog will serve as a roadmap for functional analyses of lincRNAs in genetic mouse models.
C1 [Luo, Haitao; Sun, Silong; Bu, Dechao; Zhao, Yi] Chinese Acad Sci, Inst Comp Technol, Adv Comp Res Lab, Bioinformat Res Grp, Beijing, Peoples R China.
[Li, Ping; Cao, Haiming] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Cao, HM (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM haiming.cao@nih.gov; biozy@ict.ac.cn
RI Zhao, Yi/A-2962-2011; Cao, Haiming/P-4634-2016
OI Zhao, Yi/0000-0001-6046-8420;
FU National High Technology Research and Development Program of China (863
Program) [2012AA022501]; Division of Intramural Research of the National
Heart Lung and Blood Institute of the NIH, USA [HL006103-02]
FX This work was supported by a grant from the National High Technology
Research and Development Program of China (863 Program) (No.
2012AA022501); Ping Li and Haiming Cao are funded by the Division of
Intramural Research of the National Heart Lung and Blood Institute
(HL006103-02) of the NIH, USA. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 37
TC 19
Z9 22
U1 1
U2 14
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 12
PY 2013
VL 8
IS 8
AR e70835
DI 10.1371/journal.pone.0070835
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 200UV
UT WOS:000323097300057
PM 23951020
ER
PT J
AU Li, JY
Valentin, A
Kulkarni, V
Rosati, M
Beach, RK
Alicea, C
Hannaman, D
Reed, SG
Felber, BK
Pavlakis, GN
AF Li, Jinyao
Valentin, Antonio
Kulkarni, Viraj
Rosati, Margherita
Beach, Rachel Kelly
Alicea, Candido
Hannaman, Drew
Reed, Steven G.
Felber, Barbara K.
Pavlakis, George N.
TI HIV/SIV DNA vaccine combined with protein in a co-immunization protocol
elicits highest humoral responses to envelope in mice and macaques
SO VACCINE
LA English
DT Article
DE Vaccination; Immunization; Electroporation; Antibody; Neutralizing
antibody; Adjuvant; Cellular responses; Humoral responses; Dendritic
cell maturation
ID HUMAN-IMMUNODEFICIENCY-VIRUS; RHESUS MACAQUES; IMMUNE-RESPONSES;
SIVMAC251 CHALLENGE; T-CELLS; INDUCTION; INFECTION; VIREMIA; GAG;
IMMUNOGENICITY
AB Vaccination with HIV/SIV DNAs elicits potent T-cell responses. To improve humoral immune responses, we combined DNA and protein in a co-immunization protocol using in vivo electroporation in mice and macaques. DNA&protein co-immunization induced higher antibody responses than DNA or protein alone, or DNA prime/protein boost in mice. DNA&protein co-immunization induced similar levels of cellular responses as those obtained by DNA only vaccination. The inclusion of SW or HIV Env gp120 protein did not impair the development of cellular immune responses elicited by DNA present in the vaccine regimen. In macaques, the DNA&protein co-immunization regimen also elicited higher levels of humoral responses with broader cross-neutralizing activity. Despite the improved immunogenicity of DNA&protein co-immunization, the protein formulation with the EM-005 (GLA-SE) adjuvant further increased the anti-Env humoral responses. Dissecting the contribution of EM-005, we found that its administration upregulated the expression of co-stimulatory molecules and stimulated cytokine production, especially IL-6, by dendritic cells in vivo. These terminally differentiated, mature, dendritic cells possibly promote higher levels of humoral responses, supporting the inclusion of the EM-005 adjuvant with the vaccine. Thus, DNA&protein co-immunization is a promising strategy to improve the rapidity of development, magnitude and potency of the humoral immune responses. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.
C1 [Li, Jinyao; Valentin, Antonio; Rosati, Margherita; Beach, Rachel Kelly; Pavlakis, George N.] NCI, Human Retrovirus Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21702 USA.
[Kulkarni, Viraj; Beach, Rachel Kelly; Alicea, Candido; Felber, Barbara K.] NCI, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21702 USA.
[Hannaman, Drew] ICHOR Med Syst Inc, San Diego, CA 92121 USA.
[Reed, Steven G.] Infect Dis Res Inst, Seattle, WA 98104 USA.
RP Pavlakis, GN (reprint author), NCI, POB B,Bldg 535,Room 210, Frederick, MD 21702 USA.
EM pavlakig@mail.nih.gov
FU National Cancer Institute, National Institutes of Health (NCI/NIH)
FX This work was supported by the Intramural Research Program of the
National Cancer Institute, National Institutes of Health (NCI/NIH).
NR 50
TC 24
Z9 26
U1 1
U2 9
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
J9 VACCINE
JI Vaccine
PD AUG 12
PY 2013
VL 31
IS 36
BP 3747
EP 3755
DI 10.1016/j.vaccine.2013.04.037
PG 9
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 204YT
UT WOS:000323407900019
PM 23624057
ER
PT J
AU Yao, JZ
Wlodawer, A
Guo, H
AF Yao, Jianzhuang
Wlodawer, Alexander
Guo, Hong
TI Understanding the Autocatalytic Process of Pro-kumamolisin Activation
from Molecular Dynamics and Quantum Mechanical/Molecular Mechanical
(QM/MM) Free-Energy Simulations
SO CHEMISTRY-A EUROPEAN JOURNAL
LA English
DT Article
DE acid; base catalysis; autocatalysis; enzymes; molecular dynamics;
zymogens
ID SERINE-CARBOXYL PEPTIDASE; ANGSTROM CRYSTAL-STRUCTURE; TETRAHEDRAL
ADDUCT; PROTEINASE
C1 [Yao, Jianzhuang; Guo, Hong] Univ Tennessee, Dept Biochem & Cellular & Mol Biol, Knoxville, TN 37996 USA.
[Wlodawer, Alexander] NCI, Prot Struct Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA.
RP Guo, H (reprint author), Univ Tennessee, Dept Biochem & Cellular & Mol Biol, Knoxville, TN 37996 USA.
EM hguo1@utk.edu
RI Guo, Hong/E-6357-2010
FU National Science Foundation (NSF) [0817940]; NSF; Intramural Research
Program of the NIH, National Cancer Institute, Center for Cancer
Research
FX We thank Dr. Toru Nakayama and Dr. Qin Xu for helpful discussions and
Professor Martin Karplus for a gift of the CHARMM program. This work was
supported by the National Science Foundation (NSF) (Grant number:
0817940 to H. G.) and the NSF TeraGrid resources provided by the
University of Texas at Austin, as well as by the Intramural Research
Program of the NIH, National Cancer Institute, Center for Cancer
Research.
NR 24
TC 1
Z9 1
U1 0
U2 19
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA POSTFACH 101161, 69451 WEINHEIM, GERMANY
SN 0947-6539
EI 1521-3765
J9 CHEM-EUR J
JI Chem.-Eur. J.
PD AUG 12
PY 2013
VL 19
IS 33
BP 10849
EP 10852
DI 10.1002/chem.201301310
PG 4
WC Chemistry, Multidisciplinary
SC Chemistry
GA 194IX
UT WOS:000322626500017
PM 23821374
ER
PT J
AU Karev, GP
Koonin, EV
AF Karev, Georgy P.
Koonin, Eugene V.
TI Parabolic replicator dynamics and the principle of minimum Tsallis
information gain
SO BIOLOGY DIRECT
LA English
DT Article
DE Replicator equation; Parabolic growth; Tsallis entropy; Non-extensive
statistical mechanics; MaxEnt principle
ID SELECTION; ENTROPY; GROWTH; TEMPLATES; SURVIVAL; PATTERNS; PHYSICS;
ORIGIN; LIFE
AB Background: Non-linear, parabolic (sub-exponential) and hyperbolic (super-exponential) models of prebiological evolution of molecular replicators have been proposed and extensively studied. The parabolic models appear to be the most realistic approximations of real-life replicator systems due primarily to product inhibition. Unlike the more traditional exponential models, the distribution of individual frequencies in an evolving parabolic population is not described by the Maximum Entropy (MaxEnt) Principle in its traditional form, whereby the distribution with the maximum Shannon entropy is chosen among all the distributions that are possible under the given constraints. We sought to identify a more general form of the MaxEnt principle that would be applicable to parabolic growth.
Results: We consider a model of a population that reproduces according to the parabolic growth law and show that the frequencies of individuals in the population minimize the Tsallis relative entropy (non-additive information gain) at each time moment. Next, we consider a model of a parabolically growing population that maintains a constant total size and provide an "implicit" solution for this system. We show that in this case, the frequencies of the individuals in the population also minimize the Tsallis information gain at each moment of the 'internal time" of the population.
Conclusions: The results of this analysis show that the general MaxEnt principle is the underlying law for the evolution of a broad class of replicator systems including not only exponential but also parabolic and hyperbolic systems. The choice of the appropriate entropy (information) function depends on the growth dynamics of a particular class of systems. The Tsallis entropy is non-additive for independent subsystems, i.e. the information on the subsystems is insufficient to describe the system as a whole. In the context of prebiotic evolution, this "non-reductionist" nature of parabolic replicator systems might reflect the importance of group selection and competition between ensembles of cooperating replicators.
Reviewers: This article was reviewed by Viswanadham Sridhara (nominated by Claus Wilke), Puushottam Dixit (nominated by Sergei Maslov), and Nick Grishin. For the complete reviews, see the Reviewers' Reports section.
C1 [Karev, Georgy P.; Koonin, Eugene V.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
EM koonin@ncbi.nlm.nih.gov
FU US Department of Health and Human Services
FX We thank Artem Novozhilov for critical reading of the manuscript. The
authors' research is supported by intramural funds of the US Department
of Health and Human Services (to National Library of Medicine).
NR 35
TC 2
Z9 2
U1 2
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1745-6150
J9 BIOL DIRECT
JI Biol. Direct
PD AUG 11
PY 2013
VL 8
AR 19
DI 10.1186/1745-6150-8-19
PG 11
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 207DH
UT WOS:000323577000001
PM 23937956
ER
PT J
AU Visvanathan, K
Hurley, P
Bantug, E
Brown, P
Col, NF
Cuzick, J
Davidson, NE
DeCensi, A
Fabian, C
Ford, L
Garber, J
Katapodi, M
Kramer, B
Morrow, M
Parker, B
Runowicz, C
Vogel, VG
Wade, JL
Lippman, SM
AF Visvanathan, Kala
Hurley, Patricia
Bantug, Elissa
Brown, Powel
Col, Nananda F.
Cuzick, Jack
Davidson, Nancy E.
DeCensi, Andrea
Fabian, Carol
Ford, Leslie
Garber, Judy
Katapodi, Maria
Kramer, Barnett
Morrow, Monica
Parker, Barbara
Runowicz, Carolyn
Vogel, Victor G., III
Wade, James L.
Lippman, Scott M.
TI Use of Pharmacologic Interventions for Breast Cancer Risk Reduction:
American Society of Clinical Oncology Clinical Practice Guideline
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID SURGICAL ADJUVANT BREAST; BOWEL PROJECT P-1; POSTMENOPAUSAL OSTEOPOROTIC
WOMEN; CONTINUING OUTCOMES RELEVANT; PRIMARY-CARE PHYSICIANS; PREVENTION
TRIAL; RANDOMIZED-TRIAL; TAMOXIFEN PROPHYLAXIS; CARDIOVASCULAR EVENTS;
TECHNOLOGY-ASSESSMENT
AB Purpose
To update the 2009 American Society of Clinical Oncology guideline on pharmacologic interventions for breast cancer (BC) risk reduction.
Methods
A systematic review of randomized controlled trials and meta-analyses published from June 2007 through June 2012 was completed using MEDLINE and Cochrane Collaboration Library. Primary outcome of interest was BC incidence (invasive and noninvasive). Secondary outcomes included BC mortality, adverse events, and net health benefits. Guideline recommendations were revised based on an Update Committee's review of the literature.
Results
Nineteen articles met the selection criteria. Six chemoprevention agents were identified: tamoxifen, raloxifene, arzoxifene, lasofoxifene, exemestane, and anastrozole.
Recommendations
In women at increased risk of BC age >= 35 years, tamoxifen (20 mg per day for 5 years) should be discussed as an option to reduce the risk of estrogen receptor (ER) -positive BC. In postmenopausal women, raloxifene (60 mg per day for 5 years) and exemestane (25 mg per day for 5 years) should also be discussed as options for BC risk reduction. Those at increased BC risk are defined as individuals with a 5-year projected absolute risk of BC >= 1.66% (based on the National Cancer Institute BC Risk Assessment Tool or an equivalent measure) or women diagnosed with lobular carcinoma in situ. Use of other selective ER modulators or other aromatase inhibitors to lower BC risk is not recommended outside of a clinical trial. Health care providers are encouraged to discuss the option of chemoprevention among women at increased BC risk. The discussion should include the specific risks and benefits associated with each chemopreventive agent. (C) 2013 by American Society of Clinical Oncology
C1 [Visvanathan, Kala] Johns Hopkins Med Inst, Baltimore, MD 21205 USA.
[Bantug, Elissa] Johns Hopkins Med & Sidney Kimmel Comprehens Canc, Baltimore, MD USA.
[Ford, Leslie; Kramer, Barnett] NCI, Bethesda, MD 20892 USA.
[Brown, Powel] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Col, Nananda F.] Univ New England, Biddeford, ME USA.
[Cuzick, Jack] Queen Mary Univ London, London, England.
[Davidson, Nancy E.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
[Davidson, Nancy E.] Med Ctr Canc Ctr, Pittsburgh, PA USA.
[Vogel, Victor G., III] Geisinger Med Ctr Canc Inst, Danville, PA USA.
[DeCensi, Andrea] Ente Osped Osped Galliera, Genoa, Italy.
[Fabian, Carol] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA.
[Garber, Judy] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Katapodi, Maria] Univ Michigan, Sch Nursing, Ann Arbor, MI 48109 USA.
[Morrow, Monica] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Parker, Barbara; Lippman, Scott M.] Univ Calif San Diego, Moores Canc Ctr, San Diego, CA 92103 USA.
[Runowicz, Carolyn] Florida Int Univ, Herbert Wertheim Coll Med, Miami, FL 33199 USA.
[Wade, James L.] Canc Care Specialists Cent Illinois, Decatur, IL USA.
RP Visvanathan, K (reprint author), Amer Soc Clin Oncol, 2318 Mill Rd,Suite 800, Alexandria, VA 22314 USA.
EM guidelines@asco.org
FU AstraZeneca; Novartis; Pfizer
FX Research Funding: Jack Cuzick, AstraZeneca; Judy Garber, AstraZeneca,
Novartis, Pfizer
NR 65
TC 104
Z9 105
U1 0
U2 13
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 AUG 10
PY 2013
VL 31
IS 23
BP 2942
EP +
DI 10.1200/JCO.2013.49.3122
PG 22
WC Oncology
SC Oncology
GA 301NP
UT WOS:000330539300020
PM 23835710
ER
PT J
AU Zhang, HE
Meltzer, P
Davis, S
AF Zhang, Hongen
Meltzer, Paul
Davis, Sean
TI RCircos: an R package for Circos 2D track plots
SO BMC BIOINFORMATICS
LA English
DT Article
DE Software; RCircos; R package; Circos; Genomic data visualization
ID GENOMIC DATA; GRAPHICS
AB Background: Circos is a Perl language based software package for visualizing similarities and differences of genome structure and positional relationships between genomic intervals. Running Circos requires extra data processing procedures to prepare plot data files and configure files from datasets, which limits its capability of integrating directly with other software tools such as R. Recently published R Bioconductor package ggbio provides a function to display genomic data in circular layout based on multiple other packages, which increases its complexity of usage and decreased the flexibility in integrating with other R pipelines.
Results: We implemented an R package, RCircos, using only R packages that come with R base installation. The package supports Circos 2D data track plots such as scatter, line, histogram, heatmap, tile, connectors, links, and text labels. Each plot is implemented with a specific function and input data for all functions are data frames which can be objects read from text files or generated with other R pipelines.
Conclusion: RCircos package provides a simple and flexible way to make Circos 2D track plots with R and could be easily integrated into other R data processing and graphic manipulation pipelines for presenting large-scale multi-sample genomic research data. It can also serve as a base tool to generate complex Circos images.
C1 [Zhang, Hongen; Meltzer, Paul; Davis, Sean] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Davis, S (reprint author), NCI, Genet Branch, Ctr Canc Res, NIH, Bldg 37,Room 6138,37 Convent Dr, Bethesda, MD 20892 USA.
EM sdavis2@mail.nih.gov
OI Davis, Sean/0000-0002-8991-6458
FU NCI intramural research Funding in Center for Cancer Research, National
Cancer Institute, National Institutes of Health, USA
FX This study was supported by NCI intramural research Funding in Center
for Cancer Research, National Cancer Institute, National Institutes of
Health, USA. The package was developed and tested with the Biowulf Linux
cluster at the National Institutes of Health, Bethesda, MD.
(http://biowulf.nih.gov).
NR 7
TC 56
Z9 56
U1 7
U2 26
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 AUG 10
PY 2013
VL 14
AR 244
DI 10.1186/1471-2105-14-244
PG 5
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA 209VT
UT WOS:000323789400001
PM 23937229
ER
PT J
AU Byeon, B
Wang, W
Barski, A
Ranallo, RT
Bao, K
Schones, DE
Zhao, KJ
Wu, C
Wu, WH
AF Byeon, Boseon
Wang, Wei
Barski, Artem
Ranallo, Ryan T.
Bao, Kan
Schones, Dustin E.
Zhao, Keji
Wu, Carl
Wu, Wei-Hua
TI The ATP-dependent Chromatin Remodeling Enzyme Fun30 Represses
Transcription by Sliding Promoter-proximal Nucleosomes
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID DNA END RESECTION; SACCHAROMYCES-CEREVISIAE; HISTONE VARIANTS;
CHROMOSOME-I; FREE REGIONS; GENOME; YEAST; COMPLEX; H2A.Z; POSITIONS
AB The evolutionarily conserved ATP-dependent chromatin remodeling enzyme Fun30 has recently been shown to play important roles in heterochromatin silencing and DNA repair. However, how Fun30 remodels nucleosomes is not clear. Here we report a nucleosome sliding activity of Fun30 and its role in transcriptional repression. We observed that Fun30 repressed the expression of genes involved in amino acid and carbohydrate metabolism, the stress response, and meiosis. In addition, Fun30 was localized at the 5' and 3' ends of genes and within the open reading frames of its targets. Consistent with its role in gene repression, we observed that Fun30 target genes lacked histone modifications often associated with gene activation and showed an increased level of ubiquitinated histone H2B. Furthermore, a genome-wide nucleosome mapping analysis revealed that the length of the nucleosome-free region at the 5' end of a subset of genes was changed in Fun30-depleted cells. In addition, the positions of the -1, +2, and +3 nucleosomes at the 5' end of target genes were shifted significantly, whereas the position of the +1 nucleosome remained largely unchanged in the fun30 Delta mutant. Finally, we demonstrated that affinity-purified, single-component Fun30 exhibited a nucleosome sliding activity in an ATP-dependent manner. These results define a role for Fun30 in the regulation of transcription and indicate that Fun30 remodels chromatin at the 5' end of genes by sliding promoter-proximal nucleosomes.
C1 [Byeon, Boseon; Wang, Wei; Bao, Kan; Wu, Wei-Hua] Georgia Regents Univ, Inst Mol Med & Genet, Med Coll Georgia, Dept Neurol, Augusta, GA 30912 USA.
[Barski, Artem; Schones, Dustin E.; Zhao, Keji] NHLBI, Syst Biol Ctr, Bethesda, MD 20892 USA.
[Ranallo, Ryan T.; Wu, Carl; Wu, Wei-Hua] NCI, Lab Biochem & Mol Biol, NIH, Bethesda, MD 20892 USA.
RP Wu, WH (reprint author), Georgia Regents Univ, Inst Mol Med & Genet, Med Coll Georgia, CA-3012,1462 Laney Walker Blvd, Augusta, GA 30912 USA.
EM wwu@gru.edu
OI Barski, Artem/0000-0002-1861-5316
FU NHLBI National Institutes of Health; NCI National Institutes of Health
[1K22CA122453]
FX This work was supported, in whole or in part, by NHLBI National
Institutes of Health intramural research support (to K. Z.), NCI
National Institutes of Health intramural research support (to C. W.),
and NCI National Institutes of Health Grant 1K22CA122453 (to W.-H. W.).
NR 62
TC 9
Z9 9
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 AUG 9
PY 2013
VL 288
IS 32
BP 23182
EP 23193
DI 10.1074/jbc.M113.471979
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 302IN
UT WOS:000330598200025
PM 23779104
ER
PT J
AU Seok, S
Kanamaluru, D
Xiao, Z
Ryerson, D
Choi, SE
Suino-Powell, K
Xu, HE
Veenstra, TD
Kemper, JK
AF Seok, Sunmi
Kanamaluru, Deepthi
Xiao, Zhen
Ryerson, Daniel
Choi, Sung-E
Suino-Powell, Kelly
Xu, H. Eric
Veenstra, Timothy D.
Kemper, Jongsook Kim
TI Bile Acid Signal-induced Phosphorylation of Small Heterodimer Partner by
Protein Kinase C zeta Is Critical for Epigenomic Regulation of Liver
Metabolic Genes
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID NUCLEAR-RECEPTOR-SHP; FARNESOID X RECEPTOR; OBESITY; REPRESSION;
EXPRESSION; MICE; FXR; BIOSYNTHESIS; MICRORNA-34A; CHOLESTASIS
AB Bile acids (BAs) are recently recognized key signaling molecules that control integrative metabolism and energy expenditure. BAs activate multiple signaling pathways, including those of nuclear receptors, primarily farnesoid X receptor (FXR), membrane BA receptors, and FXR-induced FGF19 to regulate the fed-state metabolism. Small heterodimer partner (SHP) has been implicated as a key mediator of these BA signaling pathways by recruitment of chromatin modifying proteins, but the key question of how SHP transduces BA signaling into repressive histone modifications at liver metabolic genes remains unknown. Here we show that protein kinase C zeta (PKC zeta) is activated by BA or FGF19 and phosphorylates SHP at Thr-55 and that Thr-55 phosphorylation is critical for the epigenomic coordinator functions of SHP. PKC zeta is coimmunopreciptitated with SHP and both are recruited to SHP target genes after bile acid or FGF19 treatment. Activated phosphorylated PKC zeta and phosphorylated SHP are predominantly located in the nucleus after FGF19 treatment. Phosphorylation at Thr-55 is required for subsequent methylation at Arg-57, a naturally occurring mutation site in metabolic syndrome patients. Thr-55 phosphorylation increases interaction of SHP with chromatin modifiers and their occupancy at selective BA-responsive genes. This molecular cascade leads to repressive modifications of histones at metabolic target genes, and consequently, decreased BA pools and hepatic triglyceride levels. Remarkably, mutation of Thr-55 attenuates these SHP-mediated epigenomic and metabolic effects. This study identifies PKC zeta as a novel key upstream regulator of BA-regulated SHP function, revealing the role of Thr-55 phosphorylation in epigenomic regulation of liver metabolism.
C1 [Seok, Sunmi; Kanamaluru, Deepthi; Ryerson, Daniel; Choi, Sung-E; Kemper, Jongsook Kim] Univ Illinois, Dept Mol & Integrat Physiol, Urbana, IL 61801 USA.
[Xiao, Zhen; Veenstra, Timothy D.] SAIC Frederick Inc, Lab Prote & Analyt Technol, Adv Technol Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Suino-Powell, Kelly; Xu, H. Eric] Van Andel Res Inst, Lab Struct Sci, Grand Rapids, MI 49503 USA.
RP Kemper, JK (reprint author), Univ Illinois, Dept Mol & Integrat Physiol, Urbana, IL 61801 USA.
EM jongsook@illinois.edu
FU National Institutes of Health [DK71662, DK66202, DK62777, DK95842];
National Institutes of Health NCI [HHSN261200800001E]
FX This work was supported, in whole or in part, by National Institutes of
Health Grants DK71662 (to H. E. X.), DK66202 (to H. E. X.), DK62777 (to
J. K. K.), and DK95842 (to J. K. K.) and federal funds from National
Institutes of Health NCI Contract HHSN261200800001E.
NR 39
TC 19
Z9 20
U1 0
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 AUG 9
PY 2013
VL 288
IS 32
BP 23252
EP 23263
DI 10.1074/jbc.M113.452037
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 302IN
UT WOS:000330598200032
PM 23824184
ER
PT J
AU Vaidyanathan, VG
Liang, FT
Beard, WA
Shock, DD
Wilson, SH
Cho, BP
AF Vaidyanathan, Vaidyanathan G.
Liang, Fengting
Beard, William A.
Shock, David D.
Wilson, Samuel H.
Cho, Bongsup P.
TI Insights into the Conformation of Aminofluorene-Deoxyguanine Adduct in a
DNA Polymerase Active Site
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID NUCLEOTIDE EXCISION-REPAIR; TRANSLESION SYNTHESIS; AROMATIC-AMINES;
STRUCTURAL INSIGHTS; MUTAGENIC RELEVANCE; KLENOW FRAGMENT; I KLENOW;
BETA; FIDELITY; REPLICATION
AB The active site conformation of the mutagenic fluoroamino-fluorene-deoxyguanine adduct (dG-FAF, N-(2'-deoxyguanosin-8-yl)-7-fluoro-2-aminofluorene) has been investigated in the presence of Klenow fragment of Escherichia coli DNA polymerase I (Kfexo(-)) and DNA polymerase beta (pol beta) using F-19 NMR, insertion assay, and surface plasmon resonance. In a single nucleotide gap, the dG-FAF adduct adopts both a major-groove-oriented and base-displaced stacked conformation, and this heterogeneity is retained upon binding pol beta. The addition of a non-hydrolysable 2'-deoxycytosine-5'-[(alpha,beta)-methyleno] triphosphate (dCMPcPP) nucleotide analog to the binary complex results in an increase of the major groove conformation of the adduct at the expense of the stacked conformation. Similar results were obtained with the addition of an incorrect dAMPcPP analog but with formation of the minor groove binding conformer. In contrast, dG-FAF adduct at the replication fork for the Kfexo(-) complex adopts a mix of the major and minor groove conformers with minimal effect upon the addition of non-hydrolysable nucleotides. For pol beta, the insertion of dCTP was preferred opposite the dG-FAF adduct in a single nucleotide gap assay consistent with 19F NMR data. Surface plasmon resonance binding kinetics revealed that pol beta binds tightly with DNA in the presence of correct dCTP, but the adduct weakens binding with no nucleotide specificity. These results provide molecular insights into the DNA binding characteristics of FAF in the active site of DNA polymerases and the role of DNA structure and sequence on its coding potential.
C1 [Vaidyanathan, Vaidyanathan G.; Liang, Fengting; Cho, Bongsup P.] Univ Rhode Isl, Coll Pharm, Dept Biomed & Pharmaceut Sci, Kingston, RI 02881 USA.
[Beard, William A.; Shock, David D.; Wilson, Samuel H.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Cho, BP (reprint author), Univ Rhode Isl, Coll Pharm, Dept Biomed & Pharmaceut Sci, Kingston, RI 02881 USA.
EM bcho@uri.edu
FU National Institutes of Health (NIH) [CA098296, P20 RR016457]; NIEHS, NIH
[Z01-ES050158, Z01-ES050161]; NIH [1U19CA105010]
FX This work was supported, in whole or in part, by National Institutes of
Health (NIH) Grants CA098296 (NCI) and P20 RR016457 (Center for Research
Resources) (to B. P. C.) and Research Projects Z01-ES050158 and
Z01-ES050161 in the Intramural Research Program of NIEHS, NIH, and in
association with NIH Grant 1U19CA105010 (to S. H. W.).
NR 61
TC 4
Z9 4
U1 0
U2 6
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 AUG 9
PY 2013
VL 288
IS 32
BP 23573
EP 23585
DI 10.1074/jbc.M113.476150
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 302IN
UT WOS:000330598200061
PM 23798703
ER
PT J
AU Luo, M
Velikovsky, CA
Yang, XB
Siddiqui, MA
Hong, X
Barchi, JJ
Gildersleeve, JC
Pancer, Z
Mariuzza, RA
AF Luo, Ming
Velikovsky, C. Alejandro
Yang, Xinbo
Siddiqui, Maqbool A.
Hong, Xia
Barchi, Joseph J., Jr.
Gildersleeve, Jeffrey C.
Pancer, Zeev
Mariuzza, Roy A.
TI Recognition of the Thomsen-Friedenreich Pancarcinoma Carbohydrate
Antigen by a Lamprey Variable Lymphocyte Receptor
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID MOLECULAR RECOGNITION; STRUCTURAL INSIGHTS; BINDING; THERMODYNAMICS;
GLYCOSYLATION; ANTIBODIES; EVOLUTION; LECTINS; SPECIFICITY; CANCER
AB Variable lymphocyte receptors (VLRs) are leucine-rich repeat proteins that mediate adaptive immunity in jawless vertebrates. VLRs were recently shown to recognize glycans, such as the tumor-associated Thomsen-Friedenreich antigen (TF alpha; Gal beta 1-3GalNAc alpha), with a selectivity rivaling or exceeding that of lectins and antibodies. To understand the basis for TF alpha recognition by one such VLR (VLRB.aGPA.23), we measured thermodynamic parameters for the binding interaction and determined the structure of the VLRB.aGPA.23-TF alpha complex to 2.2 angstrom resolution. In the structure, four tryptophan residues form a tight hydrophobic cage encasing the TF alpha disaccharide that completely excludes buried water molecules. This cage together with hydrogen bonding of sugar hydroxyls to polar side chains explains the exquisite selectivity of VLRB.aGPA.23. The topology of the glycan-binding site of VLRB.aGPA.23 differs markedly from those of lectins or antibodies, which typically consist of long, convex grooves for accommodating the oligosaccharide. Instead, the TF alpha disaccharide is sandwiched between a variable loop and the concave surface of the VLR formed by the beta-strands of the leucine-rich repeat modules. Longer oligosaccharides are predicted to extend perpendicularly across the beta-strands, requiring them to bend to match the concavity of the VLR solenoid.
C1 [Luo, Ming; Velikovsky, C. Alejandro; Yang, Xinbo; Mariuzza, Roy A.] Univ Maryland, Inst Biosci & Biotechnol Res, WM Keck Lab Struct Biol, Rockville, MD 20850 USA.
[Luo, Ming] Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei 230027, Anhui, Peoples R China.
[Luo, Ming] Univ Sci & Technol China, Sch Life Sci, Hefei 230027, Anhui, Peoples R China.
[Velikovsky, C. Alejandro; Yang, Xinbo; Mariuzza, Roy A.] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA.
[Siddiqui, Maqbool A.; Barchi, Joseph J., Jr.; Gildersleeve, Jeffrey C.] NCI, Biol Chem Lab, Ctr Canc Res, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Hong, Xia; Pancer, Zeev] Univ Maryland, Sch Med, Inst Marine & Environm Technol, Baltimore, MD 21202 USA.
[Hong, Xia; Pancer, Zeev] Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21202 USA.
RP Mariuzza, RA (reprint author), Univ Maryland, Inst Biosci & Biotechnol Res, 9600 Gudelsky Dr, Rockville, MD 20850 USA.
EM rmariuzz@umd.edu
RI Gildersleeve, Jeffrey/N-3392-2014; Barchi Jr., Joseph/N-3784-2014
FU National Institutes of Health (NIH) [AI036900, AI083892]; NIH, NCI;
National Science Foundation [MCB-0614672]; China Scholarship Council
FX This work was supported, in whole or in part, by National Institutes of
Health (NIH) Grants AI036900 (to R. A. M.) and AI083892 (to Z. P.) and
by the intramural research program of the NIH, NCI (to J. J. B. and J.
C. G.). This work was also supported by National Science Foundation
Grant MCB-0614672 (to Z. P.).; Supported by the Joint Supervision Ph.D.
Project of the China Scholarship Council.
NR 37
TC 9
Z9 9
U1 1
U2 15
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 AUG 9
PY 2013
VL 288
IS 32
BP 23597
EP 23606
DI 10.1074/jbc.M113.480467
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 302IN
UT WOS:000330598200063
PM 23782692
ER
PT J
AU Roukos, V
Voss, TC
Schmidt, CK
Lee, S
Wangsa, D
Misteli, T
AF Roukos, Vassilis
Voss, Ty C.
Schmidt, Christine K.
Lee, Seungtaek
Wangsa, Darawalee
Misteli, Tom
TI Spatial Dynamics of Chromosome Translocations in Living Cells
SO SCIENCE
LA English
DT Article
ID DOUBLE-STRAND BREAKS; DNA-PKCS; MOBILITY; RECOMBINATION; REPAIR
AB Chromosome translocations are a hallmark of cancer cells. We have developed an experimental system to visualize the formation of translocations in living cells and apply it to characterize the spatial and dynamic properties of translocation formation. We demonstrate that translocations form within hours of the occurrence of double-strand breaks (DSBs) and that their formation is cell cycle-independent. Translocations form preferentially between prepositioned genome elements, and perturbation of key factors of the DNA repair machinery uncouples DSB pairing from translocation formation. These observations generate a spatiotemporal framework for the formation of translocations in living cells.
C1 [Roukos, Vassilis; Schmidt, Christine K.; Misteli, Tom] NCI, Bethesda, MD 20892 USA.
[Voss, Ty C.] NCI, High Throughput Imaging Facil, Bethesda, MD 20892 USA.
[Lee, Seungtaek] PerkinElmer Hlth Sci Inc, Waltham, MA 02451 USA.
[Wangsa, Darawalee] NCI, Genet Branch, Bethesda, MD 20892 USA.
RP Misteli, T (reprint author), NCI, Bethesda, MD 20892 USA.
EM mistelit@mail.nih.gov
RI Roukos, Vassilis/K-6248-2012;
OI Schmidt, Christine/0000-0002-8363-7933
FU National Institutes of Health (NIH), NCI, Center for Cancer Research;
EMBO
FX We thank T. Tsukamoto, M. Jasin, E. Heard, D. Jullien, and M. Dundr for
reagents; B. J. Taylor, S. Banerjee, J. Simone, and K. McKinnon for help
with FACS experiments; T. Karpova (NCI Fluorescence Imaging Microscopy
Facility) for help with microscopy; and T. Ried and K. Meaburn for
expertise with SKY analysis and FISH. This research was supported by the
Intramural Research Program of the National Institutes of Health (NIH),
NCI, Center for Cancer Research, and by an EMBO long-term fellowship (C.
K. S.). We dedicate this work to the memory of Dr. Michael Potter, NCI,
a giant in the field of chromosome translocations.
NR 16
TC 82
Z9 82
U1 5
U2 41
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD AUG 9
PY 2013
VL 341
IS 6146
BP 660
EP 664
DI 10.1126/science.1237150
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 197XC
UT WOS:000322884800040
PM 23929981
ER
PT J
AU Kim, EJ
Kang, DW
Leucke, HF
Bond, MR
Ghosh, S
Love, DC
Ahn, JS
Kang, DO
Hanover, JA
AF Kim, Eun J.
Kang, Dong W.
Leucke, Hans F.
Bond, Michelle R.
Ghosh, Salil
Love, Dona C.
Ahn, Jong-Seog
Kang, Dae-Ook
Hanover, John A.
TI Optimizing the selectivity of DIFO-based reagents for intracellular
bioorthogonal applications
SO CARBOHYDRATE RESEARCH
LA English
DT Article
DE Copper-catalyzed azide-alkyne cycloaddition; Strain-promoted
azide-alkyne cycloaddition; O-GlcNAc; Glycoconjugates
ID FREE CLICK CHEMISTRY; AZIDE-ALKYNE CYCLOADDITION; CELL-SURFACE;
1,3-DIPOLAR CYCLOADDITIONS; TERMINAL ALKYNES; LIVING SYSTEMS; PROTEINS;
VISUALIZATION; CYCLOOCTYNES; LIGATION
AB One of the most commonly employed bioorthogonal reactions with azides is copper-catalyzed azide-alkyne [3+2] cycloaddition (CuAAC, a 'click' reaction). More recently, the strain-promoted azide-alkyne [3+2] cycloaddition (SPAAC, a copper-free 'click' reaction) was developed, in which an alkyne is sufficiently strained to promote rapid cycloaddition with an azide to form a stable triazole conjugate. In this report, we show that an internal alkyne in a strained ring system with two electron-withdrawing fluorine atoms adjacent to the carbon-carbon triple bond reacts to yield covalent adducts not only with azide moieties but also reacts with free sulfhydryl groups abundant in the cytosol. We have identified conditions that allow the enhanced reactivity to be tolerated when using such conformationally strained reagents to enhance reaction rates and selectivity for bioorthogonal applications such as O-GlcNAc detection. Published by Elsevier Ltd.
C1 [Kim, Eun J.] Daegu Univ, Dept Sci Educ Chem Major, Gyeongbuk 712714, South Korea.
[Kang, Dong W.] Catholic Univ Daegu, Dept Pharmaceut Sci & Technol, Gyeongbuk 712702, South Korea.
[Leucke, Hans F.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Bond, Michelle R.; Ghosh, Salil; Love, Dona C.; Hanover, John A.] NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA.
[Ahn, Jong-Seog] KRIBB, Biotherapeut Res Inst, Chem Biol Res Ctr, Cheongwon 363883, South Korea.
[Kang, Dae-Ook] Changwon Natl Univ, Coll Nat Sci, Dept Biochem & Hlth Sci, Chang Won 641773, South Korea.
RP Hanover, JA (reprint author), NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA.
EM jah@helix.nih.gov
FU NIDDK intramural funds (NIH); National Research Foundation of Korea
[2011-0027257]
FX This work was supported by the NIDDK intramural funds (NIH) and the
National Research Foundation of Korea (2011-0027257).
NR 39
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Z9 11
U1 0
U2 57
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0008-6215
EI 1873-426X
J9 CARBOHYD RES
JI Carbohydr. Res.
PD AUG 9
PY 2013
VL 377
BP 18
EP 27
DI 10.1016/j.carres.2013.05.014
PG 10
WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic
SC Biochemistry & Molecular Biology; Chemistry
GA 182MM
UT WOS:000321747000004
PM 23770695
ER
PT J
AU Miller, TW
Kaur, S
Ivins-O'Keefe, K
Roberts, DD
AF Miller, Thomas W.
Kaur, Sukhbir
Ivins-O'Keefe, Kelly
Roberts, David D.
TI Thrombospondin-1 is a CD47-dependent endogenous inhibitor of hydrogen
sulfide signaling in T cell activation
SO MATRIX BIOLOGY
LA English
DT Article
DE Thrombospondin-1; CD47; Hydrogen sulfide; T lymphocytes; Extracellular
signal-regulated kinase; Redox signaling
ID ISCHEMIA-REPERFUSION INJURY; CYSTATHIONINE-GAMMA-LYASE;
MICROTUBULE-ORGANIZING CENTER; INFLAMMATORY-BOWEL-DISEASE;
ANIMATION-LIKE STATE; NITRIC-OXIDE; ENDOTHELIAL-CELLS;
PLATELET-AGGREGATION; GRANULE POLARIZATION; MYOCARDIAL-ISCHEMIA
AB Thrombospondin-1 is a potent suppressor of T cell activation via its receptor CD47. However, the precise mechanism for this inhibition remains unclear. Because H2S is an endogenous potentiator of T cell activation and is necessary for full T cell activation, we hypothesized that thrombospondin-1 signaling through CD47 inhibits T cell activation by antagonizing H2S signaling. Primary T cells from thrombospondin-1 null mice were more sensitive to H2S-dependent activation assessed by proliferation and induction of interleukin-2 and CD69 mRNAs. Exogenous thrombospondin-1 inhibited H2S responses in wild type and thrombospondin-1 null T cells but enhanced the same responses in CD47 null T cells. Fibronectin, which shares integrin and glycosaminoglycan binding properties with thrombospondin-1 but not CD47 binding, did not inhibit H2S signaling. A CD47-binding peptide derived from thrombospondin-1 inhibited H2S-induced activation, whereas two other functional sequences from thrombospondin-1 enhanced H2S signaling. Therefore, engaging CD47 is necessary and sufficient for thrombospondin-1 to inhibit H2S-dependent T cell activation. H2S stimulated T cell activation by potentiating MEK-dependent ERR phosphorylation, and thrombospondin-1 inhibited this signaling in a CD47-dependent manner. Thrombospondin-1 also limited activation-dependent T cell expression of the H2S bio-synthetic enzymes cystathionine beta-synthase and cystathionine gamma-lyase, thereby limiting the autocrine role of H2S in T cell activation. Thus, thrombospondin-1 signaling through CD47 is the first identified endogenous inhibitor of H2S signaling and constitutes a novel mechanism that negatively regulates T cell activation. Published by Elsevier B.V.
C1 [Miller, Thomas W.; Kaur, Sukhbir; Ivins-O'Keefe, Kelly; Roberts, David D.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Roberts, DD (reprint author), NIH, Bldg 10 Room 2A33,10 Ctr Dr MSC1500, Bethesda, MD 20892 USA.
EM droberts@helix.nih.gov
RI Roberts, David/A-9699-2008; Miller, Thomas/G-1215-2011
OI Roberts, David/0000-0002-2481-2981; Miller, Thomas/0000-0001-8645-2785
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research.
NR 85
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Z9 14
U1 2
U2 12
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0945-053X
J9 MATRIX BIOL
JI Matrix Biol.
PD AUG 8
PY 2013
VL 32
IS 6
BP 316
EP 324
DI 10.1016/j.matbio.2013.02.009
PG 9
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 218TR
UT WOS:000324455900004
PM 23499828
ER
PT J
AU Purdue, MP
Hofmann, JN
Kemp, TJ
Chaturvedi, AK
Lan, Q
Park, JH
Pfeiffer, RM
Hildesheim, A
Pinto, LA
Rothman, N
AF Purdue, Mark P.
Hofmann, Jonathan N.
Kemp, Troy J.
Chaturvedi, Anil K.
Lan, Qing
Park, Ju-Hyun
Pfeiffer, Ruth M.
Hildesheim, Allan
Pinto, Ligia A.
Rothman, Nathaniel
TI A prospective study of 67 serum immune and inflammation markers and risk
of non-Hodgkin lymphoma
SO BLOOD
LA English
DT Article
ID GROWTH-FACTOR RECEPTOR-1; B-CELL LYMPHOMA; ANGIOGENIC FACTORS; SOLUBLE
CD30; TNF RECEPTOR; FUTURE RISK; CYTOKINES; CONSORTIUM; INTERLYMPH;
LEUKEMIA
AB Although severe immune dysregulation is an established risk factor for non-Hodgkin lymphoma (NHL), the importance of subclinical immunologic effects is unclear. We compared baseline serum levels of 67 immune and inflammation markers between 301 patients with NHL diagnosed 51 years after blood collection and 301 control patients within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. We observed associations with NHL for elevated B-cell-attracting chemokine 1 (BCA-1; fourth quartile vs first: odds ratio [OR], 2.7; 95% confidence interval [CI], 1.7-4.2; P-trend = 1.0 x 10(-6)), soluble tumor necrosis factor receptor 2 (sTNFR2; OR, 3.4; 95% CI, 2.0-5.8; P-trend = 1.1 x 10(-6)), and soluble vascular endothelial growth factor receptor 2 (sVEGFR2; OR, 2.3; 95% CI, 1.4-3.9; P-trend = .0005) that remained significant after Bonferroni correction, simultaneous model adjustment, and restriction to cases diagnosed 8 to 13 years after blood collection. Associations with other markers were observed, although none remained associated with NHL after adjustment for BCA-1, sTNFR2, and sVEGFR2. Our findings suggest that circulating BCA-1, sTNFR2, and sVEGFR2 are associated with NHL risk well in advance of diagnosis. Additional research is needed to replicate these findings and elucidate the underlying biologic mechanisms.
C1 [Purdue, Mark P.; Hofmann, Jonathan N.; Chaturvedi, Anil K.; Lan, Qing; Pfeiffer, Ruth M.; Hildesheim, Allan; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD 20850 USA.
[Kemp, Troy J.; Pinto, Ligia A.] SAIC Frederick Inc, HPV Immunol Lab, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Park, Ju-Hyun] Dungun Univ Seoul, Seoul, South Korea.
RP Purdue, MP (reprint author), NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 6E604, Rockville, MD 20850 USA.
EM purduem@mail.nih.gov
RI Hildesheim, Allan/B-9760-2015; Purdue, Mark/C-9228-2016; Chaturvedi,
Anil/J-2024-2015
OI Hildesheim, Allan/0000-0003-0257-2363; Purdue, Mark/0000-0003-1177-3108;
Chaturvedi, Anil/0000-0003-2696-8899
FU Intramural Research Program of the National Institutes of Health;
National Cancer Institute
FX This research was supported by the Intramural Research Program of the
National Institutes of Health and the National Cancer Institute.
NR 34
TC 22
Z9 22
U1 0
U2 3
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD AUG 8
PY 2013
VL 122
IS 6
BP 951
EP 957
DI 10.1182/blood-2013-01-481077
PG 7
WC Hematology
SC Hematology
GA 197VE
UT WOS:000322879100018
PM 23814017
ER
PT J
AU McDonnell, SRP
Hwang, SR
Rolland, D
Murga-Zamalloa, C
Basrur, V
Conlon, KP
Fermin, D
Wolfe, T
Raskind, A
Ruan, CH
Jiang, JK
Thomas, CJ
Hogaboam, CM
Burant, CF
Elenitoba-Johnson, KSJ
Lim, MS
AF McDonnell, Scott R. P.
Hwang, Steven R.
Rolland, Delphine
Murga-Zamalloa, Carlos
Basrur, Venkatesha
Conlon, Kevin P.
Fermin, Damian
Wolfe, Thomas
Raskind, Alexander
Ruan, Chunhai
Jiang, Jian-Kang
Thomas, Craig J.
Hogaboam, Cory M.
Burant, Charles F.
Elenitoba-Johnson, Kojo S. J.
Lim, Megan S.
TI Integrated phosphoproteomic and metabolomic profiling reveals
NPM-ALK-mediated phosphorylation of PKM2 and metabolic reprogramming in
anaplastic large cell lymphoma
SO BLOOD
LA English
DT Article
ID PYRUVATE-KINASE M2; TYROSINE PHOSPHORYLATION; TUMOR-GROWTH; AEROBIC
GLYCOLYSIS; CANCER METABOLISM; PROMOTE; DEHYDROGENASE; INHIBITION;
PROTEIN; IDENTIFICATION
AB The mechanisms underlying the pathogenesis of the constitutively active tyrosine kinase nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) expressing anaplastic large cell lymphoma are not completely understood. Here we show using an integrated phosphoproteomic and metabolomic strategy that NPM-ALK induces a metabolic shift toward aerobic glycolysis, increased lactate production, and biomass production. The metabolic shift is mediated through the anaplastic lymphoma kinase (ALK) phosphorylation of the tumor-specific isoform of pyruvate kinase (PKM2) at Y105, resulting in decreased enzymatic activity. Small molecule activation of PKM2 or expression of Y105F PKM2 mutant leads to reversal of the metabolic switch with increased oxidative phosphorylation and reduced lactate production coincident with increased cell death, decreased colony formation, and reduced tumor growth in an in vivo xenograft model. This study provides comprehensive profiling of the phosphoproteomic and metabolomic consequences of NPM-ALK expression and reveals a novel role of ALK in the regulation of multiple components of cellular metabolism. Our studies show that PKM2 is a novel substrate of ALK and plays a critical role in mediating the metabolic shift toward biomass production and tumorigenesis.
C1 [McDonnell, Scott R. P.; Hwang, Steven R.; Rolland, Delphine; Murga-Zamalloa, Carlos; Basrur, Venkatesha; Conlon, Kevin P.; Fermin, Damian; Wolfe, Thomas; Hogaboam, Cory M.; Elenitoba-Johnson, Kojo S. J.; Lim, Megan S.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.
[Raskind, Alexander; Ruan, Chunhai; Burant, Charles F.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.
[Jiang, Jian-Kang; Thomas, Craig J.] NIH, Chem Genom Ctr, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
RP Lim, MS (reprint author), Biomed Sci Res Bldg,Room 2039,109 Zina Pitcher Pl, Ann Arbor, MI 48109 USA.
EM meganlim@med.umich.edu
RI hogaboam, cory /M-3578-2014;
OI Burant, Charles/0000-0001-9189-5003
FU Michigan Regional Comprehensive Metabolomics Resource Core [1U24
DK097153]; National Institutes of Health, National Cancer Institute [R01
CA140806-01, R01 DE119249, R01 CA136905, 5T32 GM070449, 1F31
CA171373-01]; A. Alfred Taubman Institute
FX This work was supported by the Michigan Regional Comprehensive
Metabolomics Resource Core (1U24 DK097153), National Institutes of
Health, National Cancer Institute grants R01 CA140806-01 (to M.S.L), R01
DE119249, R01 CA136905 (to K.S.J.E.-J.), 5T32 GM070449 (to T.W.), and
1F31 CA171373-01 (to S.R.P.M.), and the A. Alfred Taubman Institute (to
C.F.B.).
NR 39
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Z9 20
U1 1
U2 17
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 AUG 8
PY 2013
VL 122
IS 6
BP 958
EP 968
DI 10.1182/blood-2013-01-482026
PG 11
WC Hematology
SC Hematology
GA 197VE
UT WOS:000322879100019
PM 23814019
ER
PT J
AU Lee, YT
de Vasconcellos, JF
Yuan, J
Byrnes, C
Noh, SJ
Meier, ER
Kim, KS
Rabel, A
Kaushal, M
Muljo, SA
Miller, JL
AF Lee, Y. Terry
de Vasconcellos, Jaira F.
Yuan, Joan
Byrnes, Colleen
Noh, Seung-Jae
Meier, Emily R.
Kim, Ki Soon
Rabel, Antoinette
Kaushal, Megha
Muljo, Stefan A.
Miller, Jeffery L.
TI LIN28B-mediated expression of fetal hemoglobin and production of
fetal-like erythrocytes from adult human erythroblasts ex vivo
SO BLOOD
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; SICKLE-CELL-DISEASE; BETA-THALASSEMIA;
MESSENGER-RNAS; STEM-CELLS; LIN28; IDENTIFICATION; MICRORNA; LIN-28;
GENE
AB Reactivation of fetal hemoglobin (HbF) holds therapeutic potential for sickle cell disease and beta-thalassemias. In human erythroid cells and hematopoietic organs, LIN28B and its targeted let-7 microRNA family, demonstrate regulated expression during the fetal-to-adult developmental transition. To explore the effects of LIN28B in human erythroid cell development, lentiviral transduction was used to knockdown LIN28B expression in erythroblasts cultured from human umbilical cord CD34+ cells. The subsequent reduction in LIN28B expression caused increased expression of let-7 and significantly reduced HbF expression. Conversely, LIN28B overexpression in cultured adult erythroblasts reduced the expression of let-7 and significantly increased HbF expression. Cellular maturation was maintained including enucleation. LIN28B expression in adult erythroblasts increased the expression of gamma-globin, and the HbF content of the cells rose to levels >30% of their hemoglobin. Expression of carbonic anhydrase I, glucosaminyl (N-acetyl) transferase 2, and miR-96 (three additional genes marking the transition from fetal-to-adult erythropoiesis) were reduced by LIN28B expression. The transcription factor BCL11A, a well-characterized repressor of gamma-globin expression, was significantly down-regulated. Independent of LIN28B, experimental suppression of let-7 also reduced BCL11A expression and significantly increased HbF expression. LIN28B expression regulates HbF levels and causes adult human erythroblasts to differentiate with a more fetal-like phenotype.
C1 [Lee, Y. Terry; de Vasconcellos, Jaira F.; Byrnes, Colleen; Noh, Seung-Jae; Meier, Emily R.; Kim, Ki Soon; Rabel, Antoinette; Kaushal, Megha; Miller, Jeffery L.] NIDDK, Mol Genom & Therapeut Sect, Mol Med Branch, Bethesda, MD 20892 USA.
[Yuan, Joan; Muljo, Stefan A.] NIAID, Integrat Immunobiol Unit, Immunol Lab, 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 jm7f@nih.gov
RI Muljo, Stefan/F-5671-2015
OI Muljo, Stefan/0000-0003-1013-446X
FU National Institute of Diabetes and Digestive and Kidney Diseases;
National Institute of Allergy and Infectious Diseases
FX The Intramural Research Programs of the National Institute of Diabetes
and Digestive and Kidney Diseases, and the National Institute of Allergy
and Infectious Diseases supported this work. A provisional patent
application was filed by the US government (National Institutes of
Health) in conjunction with this work.
NR 50
TC 31
Z9 31
U1 0
U2 7
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD AUG 8
PY 2013
VL 122
IS 6
BP 1034
EP 1041
DI 10.1182/blood-2012-12-472308
PG 8
WC Hematology
SC Hematology
GA 197VE
UT WOS:000322879100027
PM 23798711
ER
PT J
AU Flanders, A
Stetler-Stevenson, M
Landgren, O
AF Flanders, Aaron
Stetler-Stevenson, Maryalice
Landgren, Ola
TI Minimal residual disease testing in multiple myeloma by flow cytometry:
major heterogeneity
SO BLOOD
LA English
DT Letter
C1 [Flanders, Aaron; Landgren, Ola] NCI, Multiple Myeloma Sect, Bethesda, MD 20892 USA.
[Stetler-Stevenson, Maryalice] NCI, Flow Cytometry Sect, Bethesda, MD 20892 USA.
RP Landgren, O (reprint author), NCI, NIH, Ctr Canc Res, Metab Branch,Multiple Myeloma Sect, 9000 Rockville Pike,Bldg 10 Room 13N240, Bethesda, MD 20892 USA.
EM landgreo@mail.nih.gov
NR 5
TC 31
Z9 32
U1 0
U2 11
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD AUG 8
PY 2013
VL 122
IS 6
BP 1088
EP 1089
DI 10.1182/blood-2013-05-506170
PG 4
WC Hematology
SC Hematology
GA 197VE
UT WOS:000322879100034
PM 23929839
ER
PT J
AU Kato, GJ
Nouraie, SM
Gladwin, MT
AF Kato, Gregory J.
Nouraie, Seyed Mehdi
Gladwin, Mark T.
TI Lactate dehydrogenase and hemolysis in sickle cell disease
SO BLOOD
LA English
DT Letter
ID ANEMIA; CRISIS; DEATH
C1 [Kato, Gregory J.] NHLBI, Sickle Cell Vasc Dis Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Nouraie, Seyed Mehdi] Howard Univ, Ctr Sickle Cell Dis, Coll Med, Washington, DC USA.
[Nouraie, Seyed Mehdi] Howard Univ, Coll Med, Dept Internal Med, Washington, DC USA.
[Gladwin, Mark T.] Univ Pittsburgh, Med Ctr, Vasc Med Inst, Pittsburgh, PA USA.
RP Kato, GJ (reprint author), NIH, 9000 Rockville Pike,MSC 1476,Bldg 10 CRC,Room 5-5, Bethesda, MD 20892 USA.
EM gkato@nhlbi.nih.gov
RI Kato, Gregory/I-7615-2014
OI Kato, Gregory/0000-0003-4465-3217
NR 9
TC 11
Z9 11
U1 0
U2 9
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD AUG 8
PY 2013
VL 122
IS 6
BP 1091
EP 1092
DI 10.1182/blood-2013-05-505016
PG 4
WC Hematology
SC Hematology
GA 197VE
UT WOS:000322879100036
PM 23929841
ER
PT J
AU Grillon, C
Franco-Chaves, JA
Mateus, CF
Ionescu, DF
Zarate, CA
AF Grillon, Christian
Franco-Chaves, Jose A.
Mateus, Camilo F.
Ionescu, Dawn F.
Zarate, Carlos A.
TI Major Depression Is Not Associated with Blunting of Aversive Responses;
Evidence for Enhanced Anxious Anticipation
SO PLOS ONE
LA English
DT Article
ID FEAR-POTENTIATED STARTLE; PANIC DISORDER PATIENTS;
POSTTRAUMATIC-STRESS-DISORDER; UNIPOLAR DEPRESSION; LEARNED
HELPLESSNESS; INCREASED AMYGDALA; MODULATED STARTLE; VIETNAM VETERANS;
ACOUSTIC STARTLE; CONTEXTUAL FEAR
AB According to the emotion-context insensitivity (ECI) hypothesis, major depressive disorder (MDD) is associated with a diminished ability to react emotionally to positive stimuli and with blunting of defensive responses to threat. That defensive responses are blunted in MDD seems inconsistent with the conceptualization and diagnostic nosology of MDD. The present study tested the ECI hypothesis in MDD using a threat of shock paradigm. Twenty-eight patients with MDD (35.5+/-10.4 years) were compared with 28 controls (35.1+/-7.4 years). Participants were exposed to three conditions: no shock, predictable shock, and unpredictable shock. Startle magnitude was used to assess defensive responses. Inconsistent with the ECI hypothesis, startle potentiation to predictable and unpredictable shock was not reduced in the MDD group. Rather, MDD patients showed elevated startle throughout testing as well as increased contextual anxiety during the placement of the shock electrodes and in the predictable condition. A regression analysis indicated that illness duration and Beck depression inventory scores explained 37% (p<.005) of the variance in patients' startle reactivity. MDD is not associated with emotional blunting but rather enhanced defensive reactivity during anticipation of harm. These results do not support a strong version of the ECI hypothesis. Understanding the nature of stimuli or situations that lead to blunted or enhanced defensive reactivity will provide better insight into dysfunctional emotional experience in MDD.
C1 [Grillon, Christian] NIMH, Sect Neurobiol Fear & Anxiety, NIH, Bethesda, MD 20892 USA.
[Franco-Chaves, Jose A.; Mateus, Camilo F.; Ionescu, Dawn F.; Zarate, Carlos A.] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20892 USA.
RP Grillon, C (reprint author), NIMH, Sect Neurobiol Fear & Anxiety, NIH, Bethesda, MD 20892 USA.
EM Christian.grillon@nih.gov
RI Ionescu, Dawn/K-5675-2015
FU Intramural Research Program of the National Institutes of Mental Health
[MH002798]
FX Financial support of this study was provided by the Intramural Research
Program of the National Institutes of Mental Health (MH002798). 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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Z9 13
U1 4
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 AUG 8
PY 2013
VL 8
IS 8
AR e70969
DI 10.1371/journal.pone.0070969
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 201ER
UT WOS:000323124000036
PM 23951057
ER
PT J
AU Nishijima, T
Gatanaga, H
Shimbo, T
Komatsu, H
Endo, T
Horiba, M
Koga, M
Naito, T
Itoda, I
Tei, M
Fujii, T
Takada, K
Yamamoto, M
Miyakawa, T
Tanabe, Y
Mitsuya, H
Oka, S
AF Nishijima, Takeshi
Gatanaga, Hiroyuki
Shimbo, Takuro
Komatsu, Hirokazu
Endo, Tomoyuki
Horiba, Masahide
Koga, Michiko
Naito, Toshio
Itoda, Ichiro
Tei, Masanori
Fujii, Teruhisa
Takada, Kiyonori
Yamamoto, Masahiro
Miyakawa, Toshikazu
Tanabe, Yoshinari
Mitsuya, Hiroaki
Oka, Shinichi
CA SPARE Study Team
TI Switching Tenofovir/Emtricitabine plus Lopinavir/r to Raltegravir plus
Darunavir/r in Patients with Suppressed Viral Load Did Not Result in
Improvement of Renal Function but Could Sustain Viral Suppression: A
Randomized Multicenter Trial
SO PLOS ONE
LA English
DT Article
ID HIV-INFECTED PATIENTS; TENOFOVIR DISOPROXIL FUMARATE;
ANTIRETROVIRAL-NAIVE PATIENTS; TUBULAR DYSFUNCTION; HIV-1-INFECTED
PATIENTS; MITOCHONDRIAL TOXICITY; CREATININE CLEARANCE; SPARING REGIMEN;
THERAPY; SAFETY
AB Background: Whether tenofovir nephrotoxicity is reversible after its withdrawal is unknown. Furthermore, there are no data on the viral efficacy of raltegravir (RAL) plus ritonavir-boosted Darunavir (DRV/r) in patients with suppressed viral load.
Methods: This multicenter, randomized trial compared renal function and viral efficacy in patients with suppressed viral load treated with RAL+DRV/r and ritonavir-boosted lopinavir (LPV/r) plus tenofovir/emtricitabine (TVD), who had been previously on LPV/r+TVD. The primary endpoint was the proportion of patients with >10% improvement in estimated glomerular filtration rate (eGFR) at 48 weeks calculated with Cockcroft-Gault equation.
Results: 58 randomized and treatment-exposed patients were analyzed (28 on RAL+DRV/r and 30 on LPV/r+TVD). Greater than 10% improvement in eGFR was noted in 6 (25%) out of 24 with RAL+DRV/r and 3 (11%) of 28 with LPV/r+TVD, and the difference was not statistically significant (p=0.272, 95% CI -0.067 to 0.354). Sensitivity analyses using three other equations for eGFR showed the same results. Urinary beta 2 microglobulin, a sensitive marker of tenofovir tubulopathy, significantly improved with RAL+DRV/r than with LPV/r+TVD (-271 versus -64 mu g/gCr, p=0.026). Per protocol analysis showed that the HIV-RNA was <50 copies/mL at week 48 in all patients of both arms (24 in RAL+DRV and 29 in LPV/r+TVD).
Conclusions: Switching LPV/r+TVD to RAL+DRV/r did not significantly increase the proportion of patients who showed >10% improvement in renal function among those with relatively preserved eGFR. However, the switch improved urinary beta 2 microglobulin, suggesting that discontinuation of TDF might be beneficial in the long-term. RAL +DRV/r showed favorable viral efficacy in patients with suppressed viral load.
C1 [Nishijima, Takeshi; Gatanaga, Hiroyuki; Oka, Shinichi] Natl Ctr Global Hlth & Med, AIDS Clin Ctr, Tokyo, Japan.
[Nishijima, Takeshi; Gatanaga, Hiroyuki; Oka, Shinichi] Kumamoto Univ, Sch Med, Ctr AIDS Res, Kumamoto 860, Japan.
[Shimbo, Takuro] Natl Ctr Global Hlth & Med, Ctr Clin Sci, Dept Clin Study & Informat, Tokyo, Japan.
[Komatsu, Hirokazu] Saku Cent Hosp, Dept Community Care, Nagano, Japan.
[Endo, Tomoyuki] Hokkaido Univ Hosp, Dept Hematol, Sapporo, Hokkaido 060, Japan.
[Horiba, Masahide] Higashisaitama Natl Hosp, Div Resp Med, Saitama, Japan.
[Koga, Michiko] Univ Tokyo, Inst Med Sci, Adv Clin Res Ctr, Div Infect Dis, Tokyo, Japan.
[Naito, Toshio] Juntendo Univ, Sch Med, Dept Gen Med, Tokyo 113, Japan.
[Itoda, Ichiro] Shirakaba Clin, Tokyo, Japan.
[Tei, Masanori] Saku Cent Hosp, Dept Integrated Med, Nagano, Japan.
[Fujii, Teruhisa] Hiroshima Univ Hosp, Div Blood Transfus, Hiroshima, Japan.
[Takada, Kiyonori] Ehime Univ Hosp, Postgrad Clin Training Ctr, Matsuyama, Ehime, Japan.
[Yamamoto, Masahiro] Natl Hosp Org, Kyushu Med Ctr, Clin Res Inst, Fukuoka, Japan.
[Miyakawa, Toshikazu; Mitsuya, Hiroaki] Kumamoto Univ, Sch Med, Dept Infect Dis & Hematol, Kumamoto 860, Japan.
[Tanabe, Yoshinari] Niigata Univ, Med & Dent Hosp, Div Infect Control & Prevent, Niigata, Japan.
[Mitsuya, Hiroaki] NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA.
RP Oka, S (reprint author), Natl Ctr Global Hlth & Med, AIDS Clin Ctr, Tokyo, Japan.
EM oka@acc.ncgm.go.jp
RI Kumamoto University, CAIDS/G-8446-2013
FU Ministry of Health, Labor, and Welfare of Japan [H22-AIDS-001]
FX This work was supported by a Grant-in-Aid for the research on HIV/AIDS
(H22-AIDS-001) from the Ministry of Health, Labor, and Welfare of Japan.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 47
TC 16
Z9 17
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 AUG 8
PY 2013
VL 8
IS 8
AR e73639
DI 10.1371/journal.pone.0073639
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 201ER
UT WOS:000323124000097
PM 23951362
ER
PT J
AU White, MT
Smith, DL
AF White, Michael T.
Smith, David L.
TI Synergism from combinations of infection-blocking malaria vaccines
SO MALARIA JOURNAL
LA English
DT Article
DE Malaria; Vaccine; Infection; Pre-erythrocytic; Synergy
ID PLASMODIUM-FALCIPARUM; EFFICACY; SPOROZOITES; PROTECTION; IMMUNITY;
RATES
AB Plasmodium falciparum infections present novel challenges for vaccine development, including parasite replication dynamics not previously encountered for viral pathogens, and enormous diversity in target antigens. These challenges are illustrated by using a mathematical model to describe the association between the proportion of pre-erythrocytic or blood-stage parasites eliminated by vaccine-induced immune responses and the proportion of infections prevented. It is hypothesized that due to the requirement for all sporozoites to be eliminated to prevent infection, combining infection-blocking vaccines that confer protection through different biological mechanisms could lead to synergistic combinations of efficacy. Vaccines targeting blood-stage parasites may also combine synergistically if they combine to reduce the parasite multiplication rate to below the threshold of 1.
C1 [White, Michael T.] Univ London Imperial Coll Sci Technol & Med, MRC, Ctr Outbreak Anal & Modelling, Dept Infect Dis Epidemiol, London, England.
[Smith, David L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Smith, David L.] NIH, Fogarty Int Ctr, Baltimore, MD USA.
RP White, MT (reprint author), Univ London Imperial Coll Sci Technol & Med, MRC, Ctr Outbreak Anal & Modelling, Dept Infect Dis Epidemiol, London, England.
EM m.white08@imperial.ac.uk
RI Smith, David/L-8850-2013
OI Smith, David/0000-0003-4367-3849
FU Medical Research Council studentship; Bell & Melinda Gates Foundation
FX Dr Sandy Douglas is thanked for helpful comments on the draft
manuscript. MTW was funded by a Medical Research Council studentship and
a grant from the Bell & Melinda Gates Foundation.
NR 11
TC 3
Z9 3
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 AUG 8
PY 2013
VL 12
AR 280
DI 10.1186/1475-2875-12-280
PG 3
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA 206HG
UT WOS:000323509100001
PM 23927630
ER
PT J
AU Hu, YJ
Berndt, SI
Gustafsson, S
Ganna, A
Hirschhorn, J
North, KE
Ingelsson, E
Lin, DY
AF Hu, Yi-Juan
Berndt, Sonja I.
Gustafsson, Stefan
Ganna, Andrea
Hirschhorn, Joel
North, Kari E.
Ingelsson, Erik
Lin, Dan-Yu
CA Genetic Invest ANthropometric Trai
TI Meta-analysis of Gene-Level Associations for Rare Variants Based on
Single-Variant Statistics
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; EFFICIENCY; LOCI; MAP
AB Meta-analysis of genome-wide association studies (GWASs) has led to the discoveries of many common variants associated with complex human diseases. There is a growing recognition that identifying "causal" rare variants also requires large-scale meta-analysis. The fact that association tests with rare variants are performed at the gene level rather than at the variant level poses unprecedented challenges in the meta-analysis. First, different studies may adopt different gene-level tests, so the results are not compatible. Second, gene-level tests require multivariate statistics (i.e., components of the test statistic and their covariance matrix), which are difficult to obtain. To overcome these challenges, we propose to perform gene-level tests for rare variants by combining the results of single-variant analysis (i.e., p values of association tests and effect estimates) from participating studies. This simple strategy is possible because of an insight that multivariate statistics can be recoVered from single-variant statistics, together with the correlation matrix of the single-variant test statistics, which can be estimated from one of the participating studies or from a publicly available database. We show both theoretically and numerically that the proposed meta-analysis approach provides accurate control of the type I error and is as powerful as joint analysis of individual participant data. This approach accommodates any disease phenotype and any study design and produces all commonly used gene-level tests. An application to the GWAS summary results of the Genetic Investigation of ANthropometric Traits (GIANT) consortium reveals rare and low-frequency variants associated with human height. The relevant software is freely available.
C1 [Hu, Yi-Juan] Emory Univ, Dept Biostat & Bioinformat, Atlanta, GA 30322 USA.
[Berndt, Sonja I.] Natl Canc Inst, Natl Inst Hlth, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Gustafsson, Stefan; Ganna, Andrea; Ingelsson, Erik] Univ Uppsala Hosp, Dept Med Sci, Mol Epidemiol & Sci Life Lab, S-75185 Uppsala, Sweden.
[Ganna, Andrea] Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden.
[Hirschhorn, Joel] Childrens Hosp, Div Genet & Endocrinol, Boston, MA 02115 USA.
[Hirschhorn, Joel] Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA.
[Hirschhorn, Joel] Broad Inst, Metab Initiat & Program Med & Populat Genet, Cambridge, MA 02142 USA.
[Hirschhorn, Joel] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA.
[North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA.
[Ingelsson, Erik] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
[Lin, Dan-Yu] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA.
RP Lin, DY (reprint author), Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA.
EM lin@bios.unc.edu
RI Ripatti, Samuli/H-9446-2014; Polasek, Ozren/B-6002-2011; Tregouet,
David-Alexandre/E-3961-2016; Rudan, Igor/I-1467-2012; Feitosa,
Mary/K-8044-2012; Boehm, Bernhard/F-8750-2015; Milani, Lili/C-8759-2011;
Colaus, PsyColaus/K-6607-2013; Kiemeney, Lambertus/D-3357-2009; den
Heijer, Martin/J-8036-2015; Gudnason, Vilmundur/K-6885-2015; Deloukas,
Panos/B-2922-2013; Palmer, Lyle/K-3196-2014; Hypponen,
Elina/B-2596-2014; Strawbridge, Rona/H-5422-2012; Fall,
Tove/O-7226-2014; Medland, Sarah/C-7630-2013; Smith, Albert
Vernon/K-5150-2015;
OI Ripatti, Samuli/0000-0002-0504-1202; Polasek, Ozren/0000-0002-5765-1862;
Rudan, Igor/0000-0001-6993-6884; Feitosa, Mary/0000-0002-0933-2410;
Franke, Lude/0000-0002-5159-8802; Shungin, Dmitry/0000-0001-7900-5856;
Magi, Reedik/0000-0002-2964-6011; Kivimaki, Mika/0000-0002-4699-5627;
van Vliet-Ostaptchouk, Jana/0000-0002-7943-3153; Esko,
Tonu/0000-0003-1982-6569; Kristiansson, Kati/0000-0003-4688-107X;
Milani, Lili/0000-0002-5323-3102; Kiemeney,
Lambertus/0000-0002-2368-1326; den Heijer, Martin/0000-0003-3620-5617;
Gudnason, Vilmundur/0000-0001-5696-0084; Deloukas,
Panos/0000-0001-9251-070X; Palmer, Lyle/0000-0002-1628-3055; Hypponen,
Elina/0000-0003-3670-9399; Strawbridge, Rona/0000-0001-8506-3585;
Medland, Sarah/0000-0003-1382-380X; Medina-Gomez,
Carolina/0000-0001-7999-5538; Ouwehand, Willem/0000-0002-7744-1790;
Kleber, Marcus/0000-0003-0663-7275; Ganna, Andrea/0000-0002-8147-240X;
Hunt, Sarah/0000-0002-8350-1235; Smith, Albert
Vernon/0000-0003-1942-5845; Paternoster, Lavinia/0000-0003-2514-0889;
Lakka, Timo/0000-0002-9199-2871; Franks, Paul/0000-0002-0520-7604;
Scherag, Andre/0000-0002-9406-4704; Kumari, Meena/0000-0001-9716-1035;
Kuulasmaa, Kari/0000-0003-2165-1411; Wolffenbuttel, Bruce
H.R./0000-0001-9262-6921; Vandenput, Liesbeth/0000-0002-1712-6131
FU National Institutes of Health [R01CA082659, P01CA142538, U01HG004803,
HHSN268200625226C, UL1RR025005]; Division of Cancer Epidemiology and
Genetics, National Cancer Institute; National Heart, Lung, and Blood
Institute [HHSN26820110005C, HHSN26820110006C, HHSN26820110007C,
HHSN26820110008C, HHSN26820 110009C, HHSN268201100010C,
HHSN268201100011C, HHSN268201100012C, HHSN26800625226C, R01HL087641,
R01HL59367, R01HL086694]; National Human Genome Research Institute
[U01HG004402]
FX This research was supported by the National Institutes of Health awards
R01CA082659 (D.-Y.L.), P01CA142538 (D.-Y.L.), and U01HG004803 (D.-Y.L.,
K.E.N.) and by the Intramural Research Program of the Division of Cancer
Epidemiology and Genetics, National Cancer Institute (S.I.B.). ARIC is a
collaborative study supported by National Heart, Lung, and Blood
Institute contracts (HHSN26820110005C, HHSN26820110006C,
HHSN26820110007C, HHSN26820110008C, HHSN26820 110009C,
HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, and
HHSN26800625226C) and grants R01HL087641, R01HL59367, and R01HL086694;
National Human Genome Research Institute contract U01HG004402; and
National Institutes of Health contract HHSN268200625226C. The authors
thank the staff and participants of the ARIC study for their important
contribution. Infrastructure was partly supported by Grant Number
UL1RR025005, a component of the National Institutes of Health and the
National Institutes of Health Roadmap for Medical Research.
NR 24
TC 20
Z9 21
U1 2
U2 39
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD AUG 8
PY 2013
VL 93
IS 2
BP 236
EP 248
DI 10.1016/j.ajhg.2013.06.011
PG 13
WC Genetics & Heredity
SC Genetics & Heredity
GA 202AP
UT WOS:000323186200004
PM 23891470
ER
PT J
AU Cheng, CY
Schache, M
Ikram, MK
Young, TL
Guggenheim, JA
Vitart, V
MacGregor, S
Verhoeven, VJM
Barathi, VA
Liao, JM
Hysi, PG
Bailey-Wilson, JE
St Pourcain, B
Kemp, JP
McMahon, G
Timpson, NJ
Evans, DM
Montgomery, GW
Mishra, A
Wang, YX
Wang, JJ
Rochtchina, E
Polasek, O
Wright, AF
Amin, N
van Leeuwen, EM
Wilson, JF
Pennell, CE
van Duijn, CM
de Jong, PTVM
Vingerling, JR
Zhou, X
Chen, P
Li, RY
Tay, WT
Zheng, YF
Chew, M
Burdon, KP
Craig, JE
Iyengar, SK
Igo, RP
Lass, JH
Chew, EY
Haller, T
Mihailov, E
Metspalu, A
Wedenoja, J
Simpson, CL
Wojciechowski, R
Hohn, R
Mirshahi, A
Zeller, T
Pfeiffer, N
Lackner, KJ
Bettecken, T
Meitinger, T
Oexle, K
Pirastu, M
Portas, L
Nag, A
Williams, KM
Yonova-Doing, E
Klein, R
Klein, BE
Hosseini, SM
Paterson, AD
Makela, KM
Lehtimaki, T
Kahonen, M
Raitakari, O
Yoshimura, N
Matsuda, F
Chen, LJ
Pang, CP
Yip, SP
Yap, MKH
Meguro, A
Mizuki, N
Inoko, H
Foster, PJ
Zhao, JH
Vithana, E
Tai, ES
Fan, Q
Xu, L
Campbell, H
Fleck, B
Rudan, I
Aung, T
Hofman, A
Uitterlinden, AG
Bencic, G
Khor, CC
Forward, H
Parssinen, O
Mitche, P
Rivadeneira, F
Hewitt, AW
Williams, C
Oostra, BA
Teo, YY
Hammond, CJ
Stambolian, D
Mackey, DA
Klaver, CCW
Wong, TY
Saw, SM
Baird, PN
AF Cheng, Ching-Yu
Schache, Maria
Ikram, M. Kamran
Young, Terri L.
Guggenheim, Jeremy A.
Vitart, Veronique
MacGregor, Stuart
Verhoeven, Virginie J. M.
Barathi, Veluchamy A.
Liao, Jiemin
Hysi, Pirro G.
Bailey-Wilson, Joan E.
St Pourcain, Beate
Kemp, John P.
McMahon, George
Timpson, Nicholas J.
Evans, David M.
Montgomery, Grant W.
Mishra, Aniket
Wang, Ya Xing
Wang, Jie Jin
Rochtchina, Elena
Polasek, Ozren
Wright, Alan F.
Amin, Najaf
van Leeuwen, Elisabeth M.
Wilson, James F.
Pennell, Craig E.
van Duijn, Cornelia M.
de Jong, Paulus T. V. M.
Vingerling, Johannes R.
Zhou, Xin
Chen, Peng
Li, Ruoying
Tay, Wan-Ting
Zheng, Yingfeng
Chew, Merwyn
Burdon, Kathryn P.
Craig, Jamie E.
Iyengar, Sudha K.
Igo, Robert P., Jr.
Lass, Jonathan H., Jr.
Chew, Emily Y.
Haller, Toomas
Mihailov, Evelin
Metspalu, Andres
Wedenoja, Juho
Simpson, Claire L.
Wojciechowski, Robert
Hoehn, Rene
Mirshahi, Alireza
Zeller, Tanja
Pfeiffer, Norbert
Lackner, Karl J.
Bettecken, Thomas
Meitinger, Thomas
Oexle, Konrad
Pirastu, Mario
Portas, Laura
Nag, Abhishek
Williams, Katie M.
Yonova-Doing, Ekaterina
Klein, Ronald
Klein, Barbara E.
Hosseini, S. Mohsen
Paterson, Andrew D.
Makela, Kari-Matti
Lehtimaki, Terho
Kahonen, Mika
Raitakari, Olli
Yoshimura, Nagahisa
Matsuda, Fumihiko
Chen, Li Jia
Pang, Chi Pui
Yip, Shea Ping
Yap, Maurice K. H.
Meguro, Akira
Mizuki, Nobuhisa
Inoko, Hidetoshi
Foster, Paul J.
Zhao, Jing Hua
Vithana, Eranga
Tai, E-Shyong
Fan, Qiao
Xu, Liang
Campbell, Harry
Fleck, Brian
Rudan, Igor
Aung, Tin
Hofman, Albert
Uitterlinden, Andre G.
Bencic, Goran
Khor, Chiea-Chuen
Forward, Hannah
Parssinen, Olavi
Mitchell, Paul
Rivadeneira, Fernando
Hewitt, Alex W.
Williams, Cathy
Oostra, Ben A.
Teo, Yik-Ying
Hammond, Christopher J.
Stambolian, Dwight
Mackey, David A.
Klaver, Caroline C. W.
Wong, Tien-Yin
Saw, Seang-Mei
Baird, Paul N.
CA Consortium Refractive Error Myopia
Fuchs Genetics Multictr Study Grp
Wellcome Trust Case Control Consor
Diabet Control Complications Trial
TI Nine Loci for Ocular Axial Length Identified through Genome-wide
Association Studies, Including Shared Loci with Refractive Error
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID URBAN INDIAN POPULATION; SINGAPORE MALAY EYE; BLUE MOUNTAINS EYE; VISUAL
IMPAIRMENT; SUSCEPTIBILITY LOCI; CORNEAL CURVATURE; SPHERICAL
EQUIVALENT; CHINESE CHILDREN; MYOPIA; PREVALENCE
AB Refractive errors are common eye disorders of public health importance worldwide. Ocular axial length (AL) is the major determinant of refraction and thus of myopia and hyperopia. We conducted a meta-analysis of genome-wide association studies for AL, combining 12,531 Europeans and 8,216 Asians. We identified eight genome-wide significant loci for AL (RSPO1, C3orf26, LAMA2, GJD2, ZNRF3, CD55, MIP, and ALPPL2) and confirmed one previously reported AL locus (ZC3H11B). Of the nine loci, five (LAMA2, GJD2, CD55, ALPPL2, and ZC3H11B) were associated with refraction in 18 independent cohorts (n = 23,591). Differential gene expression was observed for these loci in minus-lens-induced myopia mouse experiments and human ocular tissues. Two of the AL genes, RSPO1 and ZNRF3, are involved in Wnt signaling, a pathway playing a major role in the regulation of eyeball size. This study provides evidence of shared genes between AL and refraction, but importantly also suggests that these traits may have unique pathways.
C1 [Cheng, Ching-Yu; Schache, Maria; Barathi, Veluchamy A.; Liao, Jiemin; Aung, Tin; Khor, Chiea-Chuen; Wong, Tien-Yin; Saw, Seang-Mei] Natl Univ Singapore, Dept Ophthalmol, Singapore 119228, Singapore.
[Cheng, Ching-Yu; Schache, Maria; Barathi, Veluchamy A.; Liao, Jiemin; Tai, E-Shyong; Aung, Tin; Khor, Chiea-Chuen; Wong, Tien-Yin; Saw, Seang-Mei] Natl Univ Hlth Syst, Singapore 119228, Singapore.
[Cheng, Ching-Yu; Zhou, Xin; Chen, Peng; Li, Ruoying; Tai, E-Shyong; Fan, Qiao; Teo, Yik-Ying; Wong, Tien-Yin; Saw, Seang-Mei] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117597, Singapore.
[Cheng, Ching-Yu; Zhou, Xin; Chen, Peng; Li, Ruoying; Tai, E-Shyong; Fan, Qiao; Teo, Yik-Ying; Wong, Tien-Yin; Saw, Seang-Mei] Natl Univ Hlth Syst, Singapore 117597, Singapore.
[Cheng, Ching-Yu; Ikram, M. Kamran; Barathi, Veluchamy A.; Liao, Jiemin; Tay, Wan-Ting; Zheng, Yingfeng; Chew, Merwyn; Vithana, Eranga; Aung, Tin; Wong, Tien-Yin; Saw, Seang-Mei] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore 168751, Singapore.
[Cheng, Ching-Yu; Ikram, M. Kamran; Saw, Seang-Mei] Duke Natl Univ Singapore, Grad Sch Med, Off Clin Sci, Ctr Quantitat Med, Singapore 169857, Singapore.
[Schache, Maria; Wang, Jie Jin; Hewitt, Alex W.; Mackey, David A.; Baird, Paul N.] Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, Melbourne, Vic 3002, Australia.
[Ikram, M. Kamran; Verhoeven, Virginie J. M.; Vingerling, Johannes R.; Klaver, Caroline C. W.] Erasmus MC, Dept Ophthalmol, NL-3000 CA Rotterdam, Netherlands.
[Young, Terri L.] Duke Univ, Med Ctr, Dept Ophthalmol, Durham, NC 27710 USA.
[Young, Terri L.] Duke Natl Univ Singapore, Grad Sch Med, Div Neurosci & Behav Disorders, Singapore 169857, Singapore.
[Guggenheim, Jeremy A.; Yap, Maurice K. H.] Hong Kong Polytech Univ, Sch Optometry, Ctr Myopia Res, Kowloon, Hong Kong, Peoples R China.
[Vitart, Veronique; Wright, Alan F.] Univ Edinburgh, Inst Genet & Mol Med, Human Genet Unit, MRC, Edinburgh EH4 2XU, Midlothian, Scotland.
[MacGregor, Stuart; Montgomery, Grant W.; Mishra, Aniket] Queensland Inst Med Res, Brisbane, Qld 4029, Australia.
[Verhoeven, Virginie J. M.; Amin, Najaf; van Leeuwen, Elisabeth M.; van Duijn, Cornelia M.; Vingerling, Johannes R.; Hofman, Albert; Uitterlinden, Andre G.; Rivadeneira, Fernando; Klaver, Caroline C. W.] Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands.
[Barathi, Veluchamy A.; Tai, E-Shyong] Duke Natl Univ Singapore, Grad Sch Med, Singapore 169857, Singapore.
[Hysi, Pirro G.; Nag, Abhishek; Williams, Katie M.; Yonova-Doing, Ekaterina; Hammond, Christopher J.] Kings Coll London, Sch Med, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England.
[Bailey-Wilson, Joan E.; Simpson, Claire L.; Wojciechowski, Robert] NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD 21224 USA.
[St Pourcain, Beate; Kemp, John P.; McMahon, George; Timpson, Nicholas J.; Evans, David M.] Univ Bristol, Sch Social & Community Med, Ctr Causal Anal Translat Epidemiol, MRC, Bristol BS8 2BN, Avon, England.
[St Pourcain, Beate; Kemp, John P.; McMahon, George; Timpson, Nicholas J.; Evans, David M.; Williams, Cathy] Univ Bristol, Sch Social & Community Med, Bristol BS8 2BN, Avon, England.
[Wang, Ya Xing; Xu, Liang] Capital Univ Med Sci, Beijing Tongren Hosp, Beijing Inst Ophthalmol, Beijing 100730, Peoples R China.
[Wang, Jie Jin; Rochtchina, Elena; Mitchell, Paul] Univ Sydney, Westmead Millennium Inst, Ctr Vis Res, Dept Ophthalmol, Sydney, NSW 2145, Australia.
[Polasek, Ozren] Univ Split, Fac Med, Split 21000, Croatia.
[Wilson, James F.; Campbell, Harry; Rudan, Igor] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh EH8 9AG, Midlothian, Scotland.
[Pennell, Craig E.; Forward, Hannah] Univ Western Australia, Sch Womens & Infants Hlth, Perth, WA 6009, Australia.
[de Jong, Paulus T. V. M.] Netherlands Inst Neurosci, NL-1105 BA Amsterdam, Netherlands.
[de Jong, Paulus T. V. M.] Univ Amsterdam, Acad Med Ctr, Dept Ophthalmol, NL-1105 AZ Amsterdam, Netherlands.
[de Jong, Paulus T. V. M.] Leids Univ, Med Ctr, NL-2300 RC Leiden, Netherlands.
[Burdon, Kathryn P.; Craig, Jamie E.] Flinders Univ S Australia, Dept Ophthalmol, Adelaide, SA 5001, Australia.
[Iyengar, Sudha K.; Igo, Robert P., Jr.; Lass, Jonathan H., Jr.] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA.
[Iyengar, Sudha K.; Lass, Jonathan H., Jr.] Case Western Reserve Univ, Dept Ophthalmol & Visual Sci, Cleveland, OH 44106 USA.
[Iyengar, Sudha K.; Lass, Jonathan H., Jr.] Univ Hosp Cleveland, Inst Eye, Cleveland, OH 44106 USA.
[Iyengar, Sudha K.] Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA.
[Iyengar, Sudha K.] Case Western Reserve Univ, Ctr Clin Invest, Cleveland, OH 44106 USA.
[Chew, Emily Y.] NEI, NIH, Bethesda, MD 20892 USA.
[Haller, Toomas; Mihailov, Evelin; Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia.
[Mihailov, Evelin] Univ Tartu, Inst Mol & Cell Biol, EE-51010 Tartu, Estonia.
[Wedenoja, Juho] Univ Helsinki, Dept Publ Hlth, Hjelt Inst, Helsinki 00014, Finland.
[Wojciechowski, Robert] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
[Hoehn, Rene; Mirshahi, Alireza; Pfeiffer, Norbert] Univ Med Ctr Mainz, Dept Ophthalmol, D-55131 Mainz, Germany.
[Zeller, Tanja] Univ Heart Ctr Hamburg, Clin Gen & Intervent Cardiol, D-20246 Hamburg, Germany.
[Lackner, Karl J.] Univ Med Ctr Mainz, Dept Clin Chem & Lab Med, D-55131 Mainz, Germany.
[Bettecken, Thomas; Meitinger, Thomas] Helmholtz Zentrum Munchen, Inst Human Genet, D-85764 Neuherberg, Germany.
[Meitinger, Thomas; Oexle, Konrad] Tech Univ Munich, Inst Human Genet, D-81675 Munich, Germany.
[Pirastu, Mario; Portas, Laura] Natl Res Council Italy, Inst Populat Genet, I-07100 Sassari, Italy.
[Klein, Ronald; Klein, Barbara E.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI 53705 USA.
[Hosseini, S. Mohsen; Paterson, Andrew D.] Univ Toronto, Hosp Sick Children, Program Genet & Genome Biol, Toronto, ON M5G 1X8, Canada.
[Hosseini, S. Mohsen; Paterson, Andrew D.] Univ Toronto, Inst Med Sci, Toronto, ON M5G 1X8, Canada.
[Makela, Kari-Matti; Lehtimaki, Terho] Univ Tampere, Tampere Univ Hosp, Filmlab Labs, Dept Clin Chem, Tampere 33520, Finland.
[Makela, Kari-Matti; Lehtimaki, Terho] Univ Tampere, Sch Med, Tampere 33520, Finland.
[Kahonen, Mika] Univ Tampere, Tampere Univ Hosp, Dept Clin Physiol, Tampere 33521, Finland.
[Kahonen, Mika] Univ Tampere, Sch Med, Tampere 33521, Finland.
[Raitakari, Olli] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku 20041, Finland.
[Raitakari, Olli] Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku 20041, Finland.
[Yoshimura, Nagahisa] Kyoto Univ, Grad Sch Med, Dept Ophthalmol & Visual Sci, Kyoto 6068507, Japan.
[Matsuda, Fumihiko] Kyoto Univ, Grad Sch Med, Dept Human Dis Genom, Kyoto 6068501, Japan.
[Chen, Li Jia] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Ophthalmol & Visual Sci, Shatin, Hong Kong, Peoples R China.
[Pang, Chi Pui] Chinese Univ Hong Kong, Hong Kong Eye Hosp, Dept Ophthalmol & Visual Sci, Kowloon, Hong Kong, Peoples R China.
[Yip, Shea Ping] Hong Kong Polytech Univ, Dept Hlth Technol & Informat, Hong Kong, Hong Kong, Peoples R China.
[Meguro, Akira; Mizuki, Nobuhisa] Yokohama City Univ, Grad Sch Med, Dept Ophthalmol & Visual Sci, Yokohama, Kanagawa 2360004, Japan.
[Inoko, Hidetoshi] Tokai Univ, Sch Med, Dept Genet Informat, Div Mol Life Sci, Tokyo, Kanagawa 2591193, Japan.
[Foster, Paul J.] Moorfields Eye Hosp, NIHR Biomed Res Ctr, London EC1V 2PD, England.
[Foster, Paul J.] UCL Inst Ophthalmol, London EC1V 2PD, England.
[Zhao, Jing Hua] Univ Cambridge, Inst Metab Sci, Epidemiol Unit, MRC, Cambridge CB2 0QQ, England.
[Tai, E-Shyong] Natl Univ Singapore, Dept Med, Singapore 119228, Singapore.
[Fleck, Brian] Princess Alexandra Eye Pavil, Edinburgh EH3 9HA, Midlothian, Scotland.
[Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands.
[Bencic, Goran] Sisters Mercy Univ Hosp, Dept Ophthalmol, Zagreb 10000, Croatia.
[Khor, Chiea-Chuen] Genome Inst Singapore, Div Human Genet, Singapore 138672, Singapore.
[Parssinen, Olavi] Univ Jyvaskyla, Dept Hlth Sci, Jyvaskyla 40014, Finland.
[Parssinen, Olavi] Univ Jyvaskyla, Gerontol Res Ctr, Jyvaskyla 40014, Finland.
[Parssinen, Olavi] Cent Hosp Cent Finland, Dept Ophthalmol, Jyvaskyla 40620, Finland.
[Hewitt, Alex W.; Mackey, David A.] Univ Western Australia, Lions Eye Inst, Ctr Ophthalmol & Visual Sci, Perth, WA 6009, Australia.
[Oostra, Ben A.] Erasmus MC, Dept Clin Genet, NL-3000 CA Rotterdam, Netherlands.
[Teo, Yik-Ying] Natl Univ Singapore, Dept Stat & Appl Probabil, Singapore 117546, Singapore.
[Stambolian, Dwight] Univ Penn, Dept Ophthalmol, Philadelphia, PA 19104 USA.
RP Saw, SM (reprint author), Natl Univ Singapore, Dept Ophthalmol, Singapore 119228, Singapore.
EM seang_mei_saw@nuhs.edu.sg; pnb@unimelb.edu.au
RI Yap, Maurice/K-4927-2016; wang, YA XING/K-9671-2016; Mackey,
David/H-5340-2014; van der Geest, Rob/J-8193-2015; Wilson, James
F/A-5704-2009; Polasek, Ozren/B-6002-2011; Montgomery,
Grant/B-7148-2008; Delcourt, Cecile/I-2627-2013; Meitinger,
Thomas/O-1318-2015; Rivadeneira, Fernando/O-5385-2015; Yip, Shea
Ping/A-1185-2016; Klaver, Caroline/A-2013-2016; Paterson,
Andrew/A-4088-2011; Fox, Laura /C-6249-2016; Hewitt, Alex/D-1936-2013;
Rudan, Igor/I-1467-2012; Mitchell, Paul/P-1498-2014; Biino,
Ginevra/B-5334-2013; Chen, Peng/E-5546-2015; Jankowski,
Janusz/H-2706-2012; Cheng, Ching-Yu/K-7017-2013; Burdon,
Kathryn/A-5026-2009; Macgregor, Stuart/C-6442-2009; Chen, Li
Jia/I-5078-2014; Pang, Chi/I-5388-2014; Deloukas, Panos/B-2922-2013;
Wang, Jie Jin/P-1499-2014; Blackwell, Jenefer/H-3015-2015; DeAngelis,
e/J-7863-2015
OI Kemp, John/0000-0002-9105-2249; Ikram, Mohammad
Kamran/0000-0003-0173-9571; Evans, David/0000-0003-0663-4621; Williams,
Katie M/0000-0003-4596-3938; Wedenoja, Juho/0000-0002-6155-0378;
Timpson, Nicholas/0000-0002-7141-9189; Tai, E
Shyong/0000-0003-2929-8966; Baird, Paul/0000-0002-1305-3502; Gillman,
Matthew/0000-0002-2340-6930; Plomin, Robert/0000-0002-0756-3629; Hohn,
Rene /0000-0003-2870-1469; St Pourcain, Beate/0000-0002-4680-3517;
Klein, Ronald/0000-0002-4428-6237; Khor, Chiea
Chuen/0000-0002-1128-4729; Hammond, Christopher/0000-0002-3227-2620;
Yap, Maurice/0000-0003-4687-4101; wang, YA XING/0000-0003-2749-7793;
Mackey, David/0000-0001-7914-4709; Hosseini, Mohsen/0000-0003-3626-9928;
Guggenheim, Jeremy/0000-0001-5164-340X; Bailey-Wilson,
Joan/0000-0002-9153-2920; Wojciechowski, Robert/0000-0002-9593-4652; van
der Geest, Rob/0000-0002-9084-5597; Wilson, James F/0000-0001-5751-9178;
Polasek, Ozren/0000-0002-5765-1862; Montgomery,
Grant/0000-0002-4140-8139; Delcourt, Cecile/0000-0002-2099-0481;
Rivadeneira, Fernando/0000-0001-9435-9441; Yip, Shea
Ping/0000-0002-2170-8185; Paterson, Andrew/0000-0002-9169-118X; Hewitt,
Alex/0000-0002-5123-5999; Rudan, Igor/0000-0001-6993-6884; Biino,
Ginevra/0000-0002-9936-946X; Chen, Peng/0000-0002-1422-4641; Jankowski,
Janusz/0000-0003-2130-9181; Cheng, Ching-Yu/0000-0003-0655-885X; Burdon,
Kathryn/0000-0001-8217-1249; Macgregor, Stuart/0000-0001-6731-8142;
Chen, Li Jia/0000-0003-3500-5840; Deloukas, Panos/0000-0001-9251-070X;
Wang, Jie Jin/0000-0001-9491-4898;
FU 23andMe
FX The authors thank the staff and participants of all studies for their
important contributions. Complete funding information and
acknowledgements are provided in the Supplemental Data. ALSPAC thanks
23andMe for funding the generation of the ALSPAC GWA data.
NR 81
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PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD AUG 8
PY 2013
VL 93
IS 2
BP 264
EP 277
DI 10.1016/j.ajhg.2013.06.016
PG 14
WC Genetics & Heredity
SC Genetics & Heredity
GA 202AP
UT WOS:000323186200006
PM 24144296
ER
PT J
AU Zariwala, MA
Gee, HY
Kurkowiak, M
Al-Mutairi, DA
Leigh, MW
Hurd, TW
Hjeij, R
Dell, SD
Chaki, M
Dougherty, GW
Adan, M
Spear, PC
Esteve-Rudd, J
Loges, NT
Rosenfeld, M
Diaz, KA
Olbrich, H
Wolf, WE
Sheridan, E
Batten, TFC
Halbritter, J
Porath, JD
Kohl, S
Lovric, S
Hwang, DY
Pittman, JE
Burns, KA
Ferkol, TW
Sagel, SD
Olivier, KN
Morgan, LC
Werner, C
Raidt, J
Pennekamp, P
Sun, ZX
Zhou, WB
Airik, R
Natarajan, S
Allen, SJ
Amirav, I
Wieczorek, D
Landwehr, K
Nielsen, K
Schwerk, N
Sertic, J
Kohler, G
Washburn, J
Levy, S
Fan, SL
Koerner-Rettberg, C
Amselem, S
Williams, DS
Mitchell, BJ
Drummond, LA
Otto, EA
Omran, H
Knowles, MR
Hildebrandt, F
AF Zariwala, Maimoona A.
Gee, Heon Yung
Kurkowiak, Malgorzata
Al-Mutairi, Dalal A.
Leigh, Margaret W.
Hurd, Toby W.
Hjeij, Rim
Dell, Sharon D.
Chaki, Moumita
Dougherty, Gerard W.
Adan, Mohamed
Spear, Philip C.
Esteve-Rudd, Julian
Loges, Niki T.
Rosenfeld, Margaret
Diaz, Katrina A.
Olbrich, Heike
Wolf, Whitney E.
Sheridan, Eamonn
Batten, Trevor F. C.
Halbritter, Jan
Porath, Jonathan D.
Kohl, Stefan
Lovric, Svjetlana
Hwang, Daw-Yang
Pittman, Jessica E.
Burns, Kimberlie A.
Ferkol, Thomas W.
Sagel, Scott D.
Olivier, Kenneth N.
Morgan, Lucy C.
Werner, Claudius
Raidt, Johanna
Pennekamp, Petra
Sun, Zhaoxia
Zhou, Weibin
Airik, Rannar
Natarajan, Sivakumar
Allen, Susan J.
Amirav, Israel
Wieczorek, Dagmar
Landwehr, Kerstin
Nielsen, Kim
Schwerk, Nicolaus
Sertic, Jadranka
Koehler, Gabriele
Washburn, Joseph
Levy, Shawn
Fan, Shuling
Koerner-Rettberg, Cordula
Amselem, Serge
Williams, David S.
Mitchell, Brian J.
Drummond, Lain A.
Otto, Edgar A.
Omran, Heymut
Knowles, Michael R.
Hildebrandt, Friedhelm
TI ZMYND10 Is Mutated in Primary Ciliary Dyskinesia and Interacts with
LRRC6
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID DYNEIN REGULATORY COMPLEX; CELL-CYCLE; MUTATIONS; CILIOGENESIS; DEFECTS;
CILIOPATHY; MOTILITY; DISEASE; HUMANS; GENES
AB Defects of motile cilia cause primary ciliary dyskinesia (PCD), characterized by recurrent respiratory infections and male infertility Using whole-exome resequencing and high-throughput mutation analysis, we identified recessive biallelic mutations in ZMYND10 in 14 families and mutations in the recently identified LRRC6 in 13 families. We show that ZMYND10 and LRRC6 interact and that certain ZMYND10 and LRRC6 mutations abrogate the interaction between the LRRC6 CS domain and the ZMYND10 C-terminal domain. Additionally ZMYND10 and LRRC6 colocalize with the centriole markers SAS6 and PCM1. Mutations in ZMYND10 result in the absence of the axonemal protein components DNAH5 and DNALI1 from respiratory cilia. Animal models support the association between ZMYND10 and human PCD, given that zmynd10 knockdown in zebrafish caused ciliary paralysis leading to cystic kidneys and otolith defects and that knockdown in Xenopus interfered with ciliogenesis. Our findings suggest that a cytoplasmic protein complex containing ZMYND10 and LRRC6 is necessary for motile ciliary function.
C1 [Zariwala, Maimoona A.] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA.
[Gee, Heon Yung; Halbritter, Jan; Porath, Jonathan D.; Kohl, Stefan; Lovric, Svjetlana; Hwang, Daw-Yang; Airik, Rannar; Hildebrandt, Friedhelm] Harvard Univ, Boston Childrens Hosp, Sch Med, Div Nephrol,Dept Med, Boston, MA 02115 USA.
[Kurkowiak, Malgorzata; Hjeij, Rim; Dougherty, Gerard W.; Loges, Niki T.; Olbrich, Heike; Werner, Claudius; Raidt, Johanna; Pennekamp, Petra; Omran, Heymut] Univ Childrens Hosp Muenster, Dept Gen Pediat, D-48149 Munster, Germany.
[Kurkowiak, Malgorzata] Polish Acad Sci, Inst Human Genet, Dept Mol & Clin Genet, PL-60479 Poznan, Poland.
[Kurkowiak, Malgorzata] Int Inst Mol & Cell Biol, PL-02109 Warsaw, Poland.
[Al-Mutairi, Dalal A.] Kuwait Univ, Fac Med, Hlth Sci Ctr, Dept Pathol, Safat 13110, Kuwait.
[Batten, Trevor F. C.] Univ Leeds, Fac Med & Hlth, Leeds Inst Genet Hlth & Therapeut, Leeds LS2 9JT, W Yorkshire, England.
[Leigh, Margaret W.; Pittman, Jessica E.] Univ N Carolina, Sch Med, Dept Pediat, Chapel Hill, NC 27599 USA.
[Hurd, Toby W.] Univ Edinburgh, Inst Genet & Mol Med, MRC, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland.
[Dell, Sharon D.] Univ Toronto, Hosp Sick Children, Dept Pediat, Toronto, ON M5G 1X8, Canada.
[Chaki, Moumita; Diaz, Katrina A.; Zhou, Weibin; Natarajan, Sivakumar; Allen, Susan J.; Otto, Edgar A.] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA.
[Adan, Mohamed; Drummond, Lain A.] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA.
[Spear, Philip C.; Mitchell, Brian J.] Northwestern Univ, Dept Cell & Mol Biol, Chicago, IL 60611 USA.
[Esteve-Rudd, Julian; Williams, David S.] Univ Calif Los Angeles, Sch Med, Jules Stein Eye Inst, Dept Ophthalmol & Neurobiol, Los Angeles, CA 90095 USA.
[Rosenfeld, Margaret] Univ Washington, Sch Med, Seattle Childrens Hosp, Seattle, WA 98105 USA.
[Wolf, Whitney E.; Burns, Kimberlie A.; Knowles, Michael R.] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC 27599 USA.
[Sheridan, Eamonn] St James Univ Hosp, Leeds Inst Mol Med, Leeds LS9 7TF, W Yorkshire, England.
[Ferkol, Thomas W.] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA.
[Sagel, Scott D.] Univ Colorado, Sch Med, Dept Pediat, Aurora, CO 80045 USA.
[Olivier, Kenneth N.] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA.
[Morgan, Lucy C.] Concord Hosp, Dept Resp Med, Concord 2139, NSW, Australia.
[Sun, Zhaoxia] Yale Univ, Dept Genet, New Haven, CT 06520 USA.
[Amirav, Israel] Bar Ilan Univ, Fac Med, Ziv Med Ctr, Dept Pediat, IL-13100 Safed, Israel.
[Wieczorek, Dagmar] Univ Duisburg Essen, Univ Klinikum Essen, Inst Human Genet, D-45122 Essen, Germany.
[Landwehr, Kerstin] Evangel Krankenhaus Bielefeld, Klin Kinder & Jugendmed, D-33617 Bielefeld, Nordrhein Westf, Germany.
[Nielsen, Kim] Copenhagen Univ Hosp, Rigshosp, Dept Paediat & Adolescent Med, Paediat Pulm Serv, DK-2100 Copenhagen, Denmark.
[Schwerk, Nicolaus] Hannover Med Sch, Univ Childrens Hosp, Dept Pneumol Allergy & Neonatol, D-30625 Hannover, Germany.
[Sertic, Jadranka] Univ Zagreb, Sch Med, Zagreb Clin Hosp, Clin Inst Lab Diag, Zagreb 10000, Croatia.
[Koehler, Gabriele] Univ Hosp Muenster, Dept Pathol, D-48149 Munster, Germany.
[Washburn, Joseph] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
[Levy, Shawn] HudsonAlpha Inst Biotechnol, Huntsville, AL 35806 USA.
[Fan, Shuling] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.
[Koerner-Rettberg, Cordula] Ruhr Univ Bochum, St Josef Hosp, Klin Kinder & Jugendmed, D-44791 Bochum, Germany.
[Amselem, Serge] Univ Paris 06, INSERM, Unite Mixte Rech S933, F-75012 Paris, France.
[Drummond, Lain A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Hildebrandt, Friedhelm] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
RP Hildebrandt, F (reprint author), Harvard Univ, Boston Childrens Hosp, Sch Med, Div Nephrol,Dept Med, Boston, MA 02115 USA.
EM knowles@med.unc.edu; friedhelm.hildebrandt@childrens.harvard.edu
RI Spear, Philip/L-5446-2014;
OI Spear, Philip/0000-0002-7657-3433; Otto, Edgar/0000-0002-2387-9973;
Batten, Trevor/0000-0003-3988-5603; Mitchell, Brian/0000-0001-6281-1536
FU National Institutes of Health (NIH) [DK068306, DK090917, DK091405,
DK053093, DK070263, EY013408, DK092808-01A1, 5 U54 HL096458-06]; NIH
from the National Center for Advancing Translational Sciences [UL1
TR000083, UL1 TR000154]; project "Studies of nucleic acids and proteins
from basic to applied research"; Foundation for Polish Science; European
Union Regional Development Fund; Department of Pathology, Faculty of
Medicine, Kuwait University; Office of the Director; Office of Rare
Diseases Research; National Heart, Lung, and Blood Institute (NHLBI);
NIH NHLBI [5 R01HL071798]; Deutsche Forschungsgemeinschaft [DFG Om 6/4,
Om 6/5, GRK1104, SFB592]; IZKF Munster; Cell Dynamics and Disease
graduate school; project SYSCILIA from the European Community
FX We are grateful to all individuals with primary ciliary dyskinesia (PCD)
and family members for their participation, as well as Michele Manion,
who founded the United States PCD Foundation. We thank the German
support group "Kartagener Syndrom und Primaere Ciliaere Dyskinesie e.V."
This research was supported by grants from the National Institutes of
Health (NIH) to F.H. (DK068306 and DK090917), to W.Z. (DK091405), to
I.A.D. (DK053093 and DK070263), to D.S.W (EY013408), and to Z.S.
(DK092808-01A1). This work was supported in part by NIH grants UL1
TR000083 and UL1 TR000154 from the National Center for Advancing
Translational Sciences. M.K. is supported by the project "Studies of
nucleic acids and proteins from basic to applied research," sponsored by
the International PhD Projects Programme of Foundation for Polish
Science. The project is cofinanced by the European Union Regional
Development Fund. D.A.M. was supported by the Department of Pathology,
Faculty of Medicine, Kuwait University. M.A.Z., M.W.L., S.D.D., M.R.,
T.W.F., S.D.S., J.E.P., K.N.O., and M.R.K. are supported by NIH research
grant 5 U54 HL096458-06, funded by the Office of the Director, and
supported by the Office of Rare Diseases Research and the National
Heart, Lung, and Blood Institute (NHLBI). M.A.Z. and M.R.K. are
supported by NIH NHLBI grant 5 R01HL071798. H.O. is supported by the
Deutsche Forschungsgemeinschaft (DFG Om 6/4 and Om 6/5, GRK1104, and
SFB592), IZKF Munster, the Cell Dynamics and Disease graduate school,
and project SYSCILIA from the European Community. Additional
acknowledgements are provided in the Supplemental Data.
NR 33
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PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD AUG 8
PY 2013
VL 93
IS 2
BP 336
EP 345
DI 10.1016/j.ajhg.2013.06.007
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 202AP
UT WOS:000323186200014
PM 23891469
ER
PT J
AU Kim, BW
Cho, H
Chung, JY
Conway, C
Ylaya, K
Kim, JH
Hewitt, SM
AF Kim, Bo Wook
Cho, Hanbyoul
Chung, Joon-Yong
Conway, Catherine
Ylaya, Kris
Kim, Jae-Hoon
Hewitt, Stephen M.
TI Prognostic assessment of hypoxia and metabolic markers in cervical
cancer using automated digital image analysis of immunohistochemistry
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Article
DE HIF-1 alpha; c-Met; Cervical cancer; Prognosis; Automated digital image
analysis
ID SQUAMOUS-CELL-CARCINOMAS; HEPATOCYTE GROWTH-FACTOR; INDUCIBLE FACTOR
1-ALPHA; C-MET OVEREXPRESSION; GENE-EXPRESSION; HUMAN-PAPILLOMAVIRUS;
COLORECTAL-CANCER; PANCREATIC-CANCER; FACTOR RECEPTOR; UTERINE CERVIX
AB Background: Hypoxia inducible factor-1 alpha (HIF-1 alpha), induced by tumor hypoxia, regulates tumor cell metabolism and metastasis by up-regulation of c-Met, carbonic anhydrase 9 (CA9) and glucose transporter 1 (GLUT1). The prognostic significance of hypoxia and metabolic markers is not clearly defined in cervical cancer. Here, we have examined the primary players in the hypoxia signaling pathway, by immunohistochemistry, but confirming their interactions, as well as defining which proteins are associated with outcome.
Methods: The study subjects were comprised of cervical intraepithelial neoplasia (CIN, n = 209), carcinoma in situ (CIS, n = 74), cervical cancer (n = 179), and matched nonadjacent normal tissues (n = 357). Immunohistochemistry (IHC) was performed to identify HIF-1 alpha, c-Met, CA9, and GLUT1. IHC scoring was performed using automated digital image analysis and the association of hypoxic markers with prognostic outcome was evaluated.
Results: HIF-1 alpha, c-Met, CA9 and GLUT1 expression were higher in cervical cancer than in CIN and normal cervix (all P < 0.001). Among these markers, expression of HIF-1 alpha and c-Met were significantly different in FIGO stage (P < 0.001 and P = 0.019, respectively) and patients with lymph node metastasis (P < 0.001 and P = 0.010, respectively). HIF-1 alpha expression was correlated with c-Met expression in cervical cancer (P < 0.001). High expression of HIF-1 alpha and c-Met showed worse 5-year overall survival rate (P = 0.047 and P = 0.005, respectively) than low expression group, but CA9 and GLUT1 did not show significant survival difference. After adjusting the prognostic covariates, c-Met was found to be an independent risk factor (HR=3.27; 95% CI, 1.05-10.23, P = 0.041) for overall survival in cervical cancer.
Conclusions: We demonstrate that c-Met correlates with HIF-1 alpha and is a poor prognostic factor in survival in cervical cancer.
C1 [Kim, Bo Wook; Chung, Joon-Yong; Conway, Catherine; Ylaya, Kris; Hewitt, Stephen M.] NIH, Tissue Array Res Program, Pathol Lab, Ctr Canc Res,Natl Canc Inst, Bethesda, MD 20892 USA.
[Kim, Bo Wook; Chung, Joon-Yong; Conway, Catherine; Ylaya, Kris; Hewitt, Stephen M.] NIH, Appl Mol Pathol Lab, Pathol Lab, Ctr Canc Res,Natl Canc Inst, Bethesda, MD 20892 USA.
[Cho, Hanbyoul; Kim, Jae-Hoon] Yonsei Univ, Gangnam Severance Hosp, Coll Med, Dept Obstet & Gynecol, Seoul 135720, South Korea.
[Kim, Bo Wook] Korea Canc Ctr Hosp, Dept Obstet & Gynecol, Seoul 139706, South Korea.
RP Kim, JH (reprint author), Yonsei Univ, Gangnam Severance Hosp, Coll Med, Dept Obstet & Gynecol, 146-92 Dogok Dong, Seoul 135720, South Korea.
EM jaehoonkim@yuhs.ac; genejock@helix.nih.gov
OI Hewitt, Stephen/0000-0001-8283-1788; Chung,
Joon-Yong/0000-0001-5041-5982
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research; basic Science Research Program through the
National Research Foundation of Korea (NRF); Ministry of Education,
Science and Technology [2011-0005230, 2011-0010286, 2011-0007146];
faculty research grants from Yonsei University College of Medicine
[3-2010-0072, 6-2011-0073]
FX This work was supported in part by Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research and grants
from the basic Science Research Program through the National Research
Foundation of Korea (NRF) funded by the Ministry of Education, Science
and Technology (2011-0005230, 2011-0010286 and 2011-0007146) and faculty
research grants from Yonsei University College of Medicine for 2010 and
2011 (3-2010-0072 and 6-2011-0073). We would like to express special
thanks to Dr. S. Pastorekova who friendly provided anti-CA9 antibodies
(M75 antibody).
NR 44
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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 AUG 8
PY 2013
VL 11
AR 185
DI 10.1186/1479-5876-11-185
PG 11
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 200ME
UT WOS:000323072300001
PM 23927384
ER
PT J
AU Casellas, R
Resch, W
Hakim, O
Nussenzweig, MC
AF Casellas, Rafael
Resch, Wolfgang
Hakim, Ofir
Nussenzweig, Michel C.
TI The Origin of B Cell Recurrent Chromosomal Translocations: Proximity
versus DNA Damage
SO MOLECULAR CELL
LA English
DT Letter
ID SEQUENCING REVEALS; REARRANGEMENTS; LYMPHOCYTES; GENOME; BREAKS
C1 [Casellas, Rafael; Resch, Wolfgang] NIAMS, NIH, Bethesda, MD 20892 USA.
[Casellas, Rafael] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Hakim, Ofir] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
[Nussenzweig, Michel C.] Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA.
[Nussenzweig, Michel C.] Rockefeller Univ, HHMI, New York, NY 10065 USA.
RP Casellas, R (reprint author), NIAMS, NIH, Bethesda, MD 20892 USA.
EM rafael.casellas@nih.gov; nussen@rockefeller.edu
FU Intramural NIH HHS [Z01 AR041148-03]
NR 9
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U1 0
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
J9 MOL CELL
JI Mol. Cell
PD AUG 8
PY 2013
VL 51
IS 3
BP 275
EP 276
DI 10.1016/j.molcel.2013.07.020
PG 2
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 200RK
UT WOS:000323086400001
PM 23932709
ER
PT J
AU Hudson, KL
Collins, FS
AF Hudson, Kathy L.
Collins, Francis S.
TI Family matters
SO NATURE
LA English
DT Editorial Material
ID GENOMIC RESEARCH; IDENTIFIABILITY
C1 [Hudson, Kathy L.; Collins, Francis S.] NIH, Bethesda, MD 20892 USA.
RP Hudson, KL (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
EM kathy.hudson@nih.gov
NR 7
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U1 1
U2 23
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD AUG 8
PY 2013
VL 500
IS 7461
BP 141
EP 142
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 197CH
UT WOS:000322825500011
PM 23925224
ER
PT J
AU Jaffe, HW
Patterson, AP
Lurie, N
AF Jaffe, Harold W.
Patterson, Amy P.
Lurie, Nicole
TI Extra oversight for H7N9 experiments
SO NATURE
LA English
DT Letter
C1 [Jaffe, Harold W.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Patterson, Amy P.] NIH, Bethesda, MD 20892 USA.
[Lurie, Nicole] US Dept HHS, Washington, DC 20201 USA.
RP Jaffe, HW (reprint author), Ctr Dis Control & Prevent, Atlanta, GA USA.
EM pattersa@od.nih.gov
NR 1
TC 4
Z9 4
U1 0
U2 17
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD AUG 8
PY 2013
VL 500
IS 7461
BP 151
EP 151
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 197CH
UT WOS:000322825500017
PM 23925232
ER
PT J
AU Rando, TA
Finkel, T
AF Rando, Thomas A.
Finkel, Toren
TI Cardiac Aging and Rejuvenation A Sense of Humors?
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
C1 [Rando, Thomas A.] Stanford Univ, Stanford, CA 94305 USA.
[Finkel, Toren] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Rando, TA (reprint author), Stanford Univ, Stanford, CA 94305 USA.
FU NIA NIH HHS [R01 AG047820, P01 AG036695, R37 AG023806]
NR 5
TC 8
Z9 8
U1 1
U2 9
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 AUG 8
PY 2013
VL 369
IS 6
BP 575
EP 576
DI 10.1056/NEJMcibr1306063
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 197HX
UT WOS:000322842000016
PM 23924010
ER
PT J
AU Cong, WN
Wang, R
Cai, H
Daimon, CM
Scheibye-Knudsen, M
Bohr, VA
Turkin, R
Wood, WH
Becker, KG
Moaddel, R
Maudsley, S
Martin, B
AF Cong, Wei-na
Wang, Rui
Cai, Huan
Daimon, Caitlin M.
Scheibye-Knudsen, Morten
Bohr, Vilhelm A.
Turkin, Rebecca
Wood, William H., III
Becker, Kevin G.
Moaddel, Ruin
Maudsley, Stuart
Martin, Bronwen
TI Long-Term Artificial Sweetener Acesulfame Potassium Treatment Alters
Neurometabolic Functions in C57BL/6J Mice
SO PLOS ONE
LA English
DT Article
ID MITOCHONDRIAL COMPLEX-I; TACHYKININ NK2 RECEPTOR; BODY-SURFACE AREA;
ALZHEIMERS-DISEASE; NONNUTRITIVE SWEETENERS; SYNAPTIC PLASTICITY;
GLUCOSE-HOMEOSTASIS; METABOLIC SYNDROME; CEREBRAL-ISCHEMIA;
ENERGY-METABOLISM
AB With the prevalence of obesity, artificial, non-nutritive sweeteners have been widely used as dietary supplements that provide sweet taste without excessive caloric load. In order to better understand the overall actions of artificial sweeteners, especially when they are chronically used, we investigated the peripheral and central nervous system effects of protracted exposure to a widely used artificial sweetener, acesulfame K (ACK). We found that extended ACK exposure (40 weeks) in normal C57BL/6J mice demonstrated a moderate and limited influence on metabolic homeostasis, including altering fasting insulin and leptin levels, pancreatic islet size and lipid levels, without affecting insulin sensitivity and bodyweight. Interestingly, impaired cognitive memory functions (evaluated by Morris Water Maze and Novel Objective Preference tests) were found in ACK-treated C57BL/6J mice, while no differences in motor function and anxiety levels were detected. The generation of an ACK-induced neurological phenotype was associated with metabolic dysregulation (glycolysis inhibition and functional ATP depletion) and neurosynaptic abnormalities (dysregulation of TrkB-mediated BDNF and Akt/Erk-mediated cell growth/survival pathway) in hippocampal neurons. Our data suggest that chronic use of ACK could affect cognitive functions, potentially via altering neuro-metabolic functions in male C57BL/6J mice.
C1 [Cong, Wei-na; Wang, Rui; Cai, Huan; Daimon, Caitlin M.; Turkin, Rebecca; Martin, Bronwen] NIA, Metab Unit, Clin Invest Lab, Baltimore, MD 21224 USA.
[Scheibye-Knudsen, Morten; Bohr, Vilhelm A.] NIA, Sect DNA Repair, Lab Mol Gerontol, Baltimore, MD 21224 USA.
[Wood, William H., III; Becker, Kevin G.] NIA, Gene Express & Genom Unit, Genet Lab, Baltimore, MD 21224 USA.
[Maudsley, Stuart] NIA, Receptor Pharmacol Unit, Neurosci Lab, Baltimore, MD 21224 USA.
[Moaddel, Ruin] NIA, Bioanalyt Chem & Drug Discovery Sect, Clin Invest Lab, Baltimore, MD 21224 USA.
RP Martin, B (reprint author), NIA, Metab Unit, Clin Invest Lab, Baltimore, MD 21224 USA.
EM martinbro@mail.nih.gov
RI Cai, Huan/B-6578-2016;
OI Cai, Huan/0000-0001-7731-8891; Scheibye-Knudsen,
Morten/0000-0002-6637-1280; Becker, Kevin/0000-0002-6794-6656
FU Intramural Research Program of the National Institute on Aging at the
National Institutes of Health
FX This work was carried out with the support of the Intramural Research
Program of the National Institute on Aging at 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 89
TC 7
Z9 7
U1 2
U2 53
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 AUG 7
PY 2013
VL 8
IS 8
AR e70257
DI 10.1371/journal.pone.0070257
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 200ZE
UT WOS:000323109700025
PM 23950916
ER
PT J
AU Graf, EH
Pace, MJ
Peterson, BA
Lynch, LJ
Chukwulebe, SB
Mexas, AM
Shaheen, F
Martin, JN
Deeks, SG
Connors, M
Migueles, SA
O'Doherty, U
AF Graf, Erin H.
Pace, Matthew J.
Peterson, Bennett A.
Lynch, Lindsay J.
Chukwulebe, Steve B.
Mexas, Angela M.
Shaheen, Farida
Martin, Jeffrey N.
Deeks, Steven G.
Connors, Mark
Migueles, Stephen A.
O'Doherty, Una
TI Gag-Positive Reservoir Cells Are Susceptible to HIV-Specific Cytotoxic T
Lymphocyte Mediated Clearance
SO PLOS ONE
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; IN-VIVO; ANTIRETROVIRAL THERAPY; ELITE
CONTROLLERS; PERIPHERAL-BLOOD; LATENT INFECTION; PLASMA VIREMIA; IMMUNE
CONTROL; EX-VIVO; REPLICATION
AB Resting CD4+T cells infected with HIV persist in the presence of suppressive anti-viral therapy (ART) and are barriers to a cure. One potential curative approach, therapeutic vaccination, is fueled by recognition of the ability of a subset of elite controllers (EC) to control virus without therapy due to robust anti-HIV immune responses. Controllers have low levels of integrated HIV DNA and low levels of replication competent virus, suggesting a small reservoir. As our recent data indicates some reservoir cells can produce HIV proteins (termed GPR cells for Gag-positive reservoir cells), we hypothesized that a fraction of HIV-expressing resting CD4+T cells could be efficiently targeted and cleared in individuals who control HIV via anti-HIV cytotoxic T lymphocytes (CTL). To test this we examined if superinfected resting CD4+T cells from EC express HIV Gag without producing infectious virus and the susceptibility of these cells to CTL. We found that resting CD4+T cells expressed HIV Gag and were cleared by autologous CD8+T cells from EC. Importantly, we found the extent of CTL clearance in our in vitro assay correlates with in vivo reservoir size and that a population of Gag expressing resting CD4+T cells exists in vivo in patients well controlled on therapy.
C1 [Graf, Erin H.; Pace, Matthew J.; Lynch, Lindsay J.; Chukwulebe, Steve B.; Mexas, Angela M.; O'Doherty, Una] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
[Peterson, Bennett A.; Connors, Mark; Migueles, Stephen A.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Shaheen, Farida] Univ Penn, Ctr AIDS Res, Philadelphia, PA 19104 USA.
[Martin, Jeffrey N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Deeks, Steven G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
RP O'Doherty, U (reprint author), Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
EM unao@mail.med.upenn.edu
FU National Institutes of Health (NIH) [AI087461]; NIH T32 training grant
[AI00762]; Merck
FX This work presented was funded by the National Institutes of Health
(NIH) grant AI087461, the NIH T32 training grant AI00762, and Merck. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 45
TC 19
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U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 7
PY 2013
VL 8
IS 8
AR e71879
DI 10.1371/journal.pone.0071879
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 200ZE
UT WOS:000323109700122
PM 23951263
ER
PT J
AU Meier, ER
Byrnes, C
Lee, YT
Wright, EC
Schechter, AN
Luban, NLC
Miller, JL
AF Meier, Emily Riehm
Byrnes, Colleen
Lee, Y. Terry
Wright, Elizabeth C.
Schechter, Alan N.
Luban, Naomi L. C.
Miller, Jeffery L.
TI Increased Reticulocytosis during Infancy Is Associated with Increased
Hospitalizations in Sickle Cell Anemia Patients during the First Three
Years of Life
SO PLOS ONE
LA English
DT Article
ID FETAL-HEMOGLOBIN; ADVERSE OUTCOMES; DISEASE; CHILDREN; COHORT;
PREDICTION; SEVERITY; TRIAL
AB Objective: Among older children with sickle cell anemia, leukocyte counts, hemoglobin, and reticulocytosis have previously been suggested as disease severity markers. Here we explored whether these blood parameters may be useful to predict early childhood disease severity when tested in early infancy, defined as postnatal ages 60-180 days.
Study Design: Data from fifty-nine subjects who were followed at Children's National Medical Center's Sickle Cell Program for at least three years was retrospectively analyzed. Comparisons were made between white blood cell counts, hemoglobin and reticulocyte levels measured at ages 60-180 days and the clinical course of sickle cell anemia during infancy and childhood.
Results: A majority of subjects had demonstrable anemia with increased reticulocytosis. Only increased absolute reticulocyte levels during early infancy were associated with a significant increase in hospitalization during the first three years of life. Higher absolute reticulocyte counts were also associated with a markedly shorter time to first hospitalizations and a four-fold higher cumulative frequency of clinical manifestations over the first three years of life. No significant increase in white blood cell counts was identified among the infant subjects.
Conclusions: These data suggest that during early infancy, increased reticulocytosis among asymptomatic SCA subjects is associated with increased severity of disease in childhood.
C1 [Meier, Emily Riehm; Byrnes, Colleen; Lee, Y. Terry; Schechter, Alan N.; Miller, Jeffery L.] NIDDK, Mol Med Branch, NIH, Bethesda, MD USA.
[Meier, Emily Riehm; Luban, Naomi L. C.] Childrens Natl Med Ctr, Ctr Canc & Blood Disorders, Washington, DC 20010 USA.
[Wright, Elizabeth C.] NIDDK, Off Director, NIH, Bethesda, MD USA.
[Meier, Emily Riehm; Luban, Naomi L. C.] George Washington Univ, Med Ctr, Dept Pediat, Washington, DC 20037 USA.
RP Miller, JL (reprint author), NIDDK, Mol Med Branch, NIH, Bethesda, MD USA.
EM jm7f@nih.gov
OI Schechter, Alan N/0000-0002-5235-9408
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases; Marshall B. Coyne Foundation
FX The Intramural Research Program of the National Institute of Diabetes
and Digestive and Kidney Diseases supported this work. Emily R. Meier is
also supported by funds from the Marshall B. Coyne Foundation. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 28
TC 6
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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 AUG 7
PY 2013
VL 8
IS 8
AR e70794
DI 10.1371/journal.pone.0070794
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 200ZE
UT WOS:000323109700054
PM 23951011
ER
PT J
AU Smith, DL
Perkins, TA
Tusting, LS
Scott, TW
Lindsay, SW
AF Smith, David L.
Perkins, T. Alex
Tusting, Lucy S.
Scott, Thomas W.
Lindsay, Steven W.
TI Mosquito Population Regulation and Larval Source Management in
Heterogeneous Environments
SO PLOS ONE
LA English
DT Article
ID DAR-ES-SALAAM; AEDES-AEGYPTI DIPTERA; LIFE TABLE MODEL; MALARIA
TRANSMISSION; VECTOR CONTROL; CULEX-TRITAENIORHYNCHUS;
ANOPHELES-STEPHENSI; SIMULATION-MODEL; ESSENTIAL OILS; LARGE-SCALE
AB An important question for mosquito population dynamics, mosquito-borne pathogen transmission and vector control is how mosquito populations are regulated. Here we develop simple models with heterogeneity in egg laying patterns and in the responses of larval populations to crowding in aquatic habitats. We use the models to evaluate how such heterogeneity affects mosquito population regulation and the effects of larval source management (LSM). We revisit the notion of a carrying capacity and show how heterogeneity changes our understanding of density dependence and the outcome of LSM. Crowding in and productivity of aquatic habitats is highly uneven unless egg-laying distributions are fine-tuned to match the distribution of habitats' carrying capacities. LSM reduces mosquito population density linearly with coverage if adult mosquitoes avoid laying eggs in treated habitats, but quadratically if eggs are laid in treated habitats and the effort is therefore wasted (i.e., treating 50% of habitat reduces mosquito density by approximately 75%). Unsurprisingly, targeting (i.e. treating a subset of the most productive pools) gives much larger reductions for similar coverage, but with poor targeting, increasing coverage could increase adult mosquito population densities if eggs are laid in higher capacity habitats. Our analysis suggests that, in some contexts, LSM models that accounts for heterogeneity in production of adult mosquitoes provide theoretical support for pursuing mosquito-borne disease prevention through strategic and repeated application of modern larvicides.
C1 [Smith, David L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
[Smith, David L.] Johns Hopkins Bloomberg Sch Publ Hlth, Malaria Res Inst, Baltimore, MD USA.
[Smith, David L.; Perkins, T. Alex; Scott, Thomas W.; Lindsay, Steven W.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Perkins, T. Alex; Scott, Thomas W.] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA.
[Tusting, Lucy S.] London Sch Hyg & Trop Med, Dept Dis Control, London WC1, England.
[Lindsay, Steven W.] Univ Durham, Sch Biol & Biomed Sci, Durham, England.
RP Smith, DL (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
EM dlsmith@jhsph.edu
RI Smith, David/L-8850-2013;
OI Smith, David/0000-0003-4367-3849; Tusting, Lucy/0000-0002-6897-8625
FU Bloomberg Family Foundation; National Institutes of Health/National
Institute of Allergy and Infectious Diseases [U19AI089674]; Research and
Policy for Infectious Disease Dynamics (RAPIDD) program of the Science
and Technology Directorate, Department of Homeland Security; Fogarty
International Center, National Institutes of Health
FX DLS acknowledges funding from the Bloomberg Family Foundation. DLS and
SWL acknowledge funding from National Institutes of Health/National
Institute of Allergy and Infectious Diseases (U19AI089674). DLS, TAP,
SWL, and TWS acknowledge funding from the Research and Policy for
Infectious Disease Dynamics (RAPIDD) program of the Science and
Technology Directorate, Department of Homeland Security, and the Fogarty
International Center, National Institutes of Health.
NR 51
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U1 0
U2 37
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 AUG 7
PY 2013
VL 8
IS 8
AR e71247
DI 10.1371/journal.pone.0071247
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 200ZE
UT WOS:000323109700089
PM 23951118
ER
PT J
AU Hoffman, DA
AF Hoffman, Dax A.
TI K+ Channel Regulation of Multicompartmental Signal Integration
SO NEURON
LA English
DT Editorial Material
ID NEOCORTICAL PYRAMIDAL NEURONS; DENDRITIC INTEGRATION; ACTION-POTENTIALS;
PLASTICITY; INPUT
AB Determining how neurons integrate different streams of information is critical to understanding circuit computational functions. In this issue of Neuron, Harnett et al. (2013) show that voltage-gated K+ channels control multiple layers of dendritic integration in layer 5 pyramidal neurons.
C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Neurophysiol & Biophys Sect, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
RP Hoffman, DA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Neurophysiol & Biophys Sect, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
EM hoffmand@mail.nih.gov
RI Hoffman, Dax/E-5155-2011
OI Hoffman, Dax/0000-0001-6999-2157
FU Intramural NIH HHS [Z99 HD999999]
NR 15
TC 1
Z9 1
U1 0
U2 11
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 AUG 7
PY 2013
VL 79
IS 3
BP 403
EP 405
DI 10.1016/j.neuron.2013.07.017
PG 3
WC Neurosciences
SC Neurosciences & Neurology
GA 200QX
UT WOS:000323085100001
PM 23931989
ER
PT J
AU Britt, JP
Bonci, A
AF Britt, Jonathan P.
Bonci, Antonello
TI Alcohol and Tobacco: How Smoking May Promote Excessive Drinking
SO NEURON
LA English
DT Editorial Material
ID NICOTINE; ETHANOL; DEPENDENCE
AB Cigarette smokers tend to drink more alcohol than their nonsmoking peers. In this issue of Neuron, Doyon et al. (2013) found that nicotine-induced increases in stress hormones can augment ethanol self-administration in rats, suggesting that a drug interaction may contribute to this phenomenon.
C1 [Britt, Jonathan P.; Bonci, Antonello] NIDA, Intramural Res Program, Cellular Neurobiol Res Branch, Baltimore, MD 21224 USA.
[Bonci, Antonello] Johns Hopkins Univ, Solomon H Snyder Neurosci Inst, Sch Med, Baltimore, MD 21205 USA.
RP Bonci, A (reprint author), NIDA, Intramural Res Program, Cellular Neurobiol Res Branch, Baltimore, MD 21224 USA.
EM antonello.bonci@nih.gov
RI Britt, Jonathan/D-8877-2011
OI Britt, Jonathan/0000-0003-3044-9565
FU Intramural Research Program of the National Institute of Health,
National Institute on Drug Abuse
FX This work was supported by the Intramural Research Program of the
National Institute of Health, National Institute on Drug Abuse.
NR 12
TC 3
Z9 3
U1 0
U2 11
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 AUG 7
PY 2013
VL 79
IS 3
BP 406
EP 407
DI 10.1016/j.neuron.2013.07.018
PG 2
WC Neurosciences
SC Neurosciences & Neurology
GA 200QX
UT WOS:000323085100002
PM 23931990
ER
PT J
AU Pan, BF
Geleoc, GS
Asai, Y
Horwitz, GC
Kurima, K
Ishikawa, K
Kawashima, Y
Griffith, AJ
Holt, JR
AF Pan, Bifeng
Geleoc, Gwenaelle S.
Asai, Yukako
Horwitz, Geoffrey C.
Kurima, Kiyoto
Ishikawa, Kotaro
Kawashima, Yoshiyuki
Griffith, Andrew J.
Holt, Jeffrey R.
TI TMC1 and TMC2 Are Components of the Mechanotransduction Channel in Hair
Cells of the Mammalian Inner Ear
SO NEURON
LA English
DT Article
ID MECHANOELECTRICAL TRANSDUCER CHANNELS; MECHANOSENSITIVE CHANNELS;
FUNCTIONAL MATURATION; SENSORY TRANSDUCTION; MOUSE COCHLEA; C. ELEGANS;
ADAPTATION; CALCIUM; DOMINANT; DEAFNESS
AB Sensory transduction in auditory and vestibular hair cells requires expression of transmembrane channel-like (Tmc) 1 and 2 genes, but the function of these genes is unknown. To investigate the hypothesis that TMC1 and TMC2 proteins are components of the mechanosensitive ion channels that convert mechanical information into electrical signals, we recorded whole-cell and single-channel currents from mouse hair cells that expressed Tmc1, Tmc2, or mutant Tmc1. Cells that expressed Tmc2 had high calcium permeability and large single-channel currents, while cells with mutant Tmc1 had reduced calcium permeability and reduced single-channel currents. Cells that expressed Tmc1 and Tmc2 had a broad range of single-channel currents, suggesting multiple heteromeric assemblies of TMC subunits. The data demonstrate TMC1 and TMC2 are components of hair cell transduction channels and contribute to permeation properties. Gradients in TMC channel composition may also contribute to variation in sensory transduction along the tonotopic axis of the mammalian cochlea.
C1 [Pan, Bifeng; Geleoc, Gwenaelle S.; Asai, Yukako; Horwitz, Geoffrey C.; Holt, Jeffrey R.] Harvard Univ, Boston Childrens Hosp, Sch Med, Dept Otolaryngol,FM Kirby Neurobiol Ctr, Boston, MA 02115 USA.
[Kurima, Kiyoto; Ishikawa, Kotaro; Kawashima, Yoshiyuki; Griffith, Andrew J.] Natl Inst Deafness & Other Commun Disorders, Otolaryngol Branch, NIH, Rockville, MD 20850 USA.
RP Griffith, AJ (reprint author), Natl Inst Deafness & Other Commun Disorders, Otolaryngol Branch, NIH, 5 Res Court,Room 2B-29, Rockville, MD 20850 USA.
EM griffita@nidcd.nih.gov; jeffrey.holt@childrens.harvard.edu
FU NIDCD [Z01-DC000060-10]; NIH [R01-DC05439, R01-DC008853]
FX We thank Erin Child for technical assistance, Lin Huang for assistance
with statistical analysis, and Martin Hrabe de Angelis and Helmut Fuchs
for providing Beethoven mice. We thank John Assad, David Clapham, David
Corey, Tom Friedman, Matt Kelley, Tom Schwarz, and Clifford Woolf for
helpful discussions and critical review of an earlier version of the
manuscript. This work was supported by NIDCD intramural research funds
Z01-DC000060-10 (A.J.G.); NIH grants R01-DC05439 (J.R.H.) and
R01-DC008853 (G.S.G.). K.K. and A.J.G. hold US Patents: 7,166,433
(Transductin-2 and Applications to Hereditary Deafness; abandoned in
2009), 7,192,705 (Transductin-1 and Applications to Hereditary
Deafness), and 7,659,115 (Nucleic Acid Encoding Human Transductin-1
Polypeptide). These patents have never been licensed and generate no
income or royalties. B.P. collected all electrophysiology data from
inner hair cells and helped analyze data. G.S.G. collected
electrophysiology data from vestibular hair cells and helped analyze the
data. G.C.H. collected electrophysiology data from vestibular hair
cells, performed ABRs, and helped analyze data. Y.A. generated
adenoviral vectors and performed qRT-PCR experiments. K.K. generated Tmc
constructs. K.I. performed cell count analysis of Tmc1 mutant mice. Y.K.
acquired SEM images of hair cells. A.J.G. contributed to conception of
the study and provided critical comments on the data and manuscript.
J.R.H. conceived and designed the experiments, analyzed the data,
generated the figures, and wrote the paper. All authors provided
comments and approved the final submission of the manuscript.
NR 40
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U1 4
U2 30
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
J9 NEURON
JI Neuron
PD AUG 7
PY 2013
VL 79
IS 3
BP 504
EP 515
DI 10.1016/j.neuron.2013.06.019
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 200QX
UT WOS:000323085100011
PM 23871232
ER
PT J
AU Hong, CH
Falvey, C
Harris, TB
Simonsick, EM
Satterfield, S
Ferrucci, L
Metti, AL
Patel, KV
Yaffe, K
AF Hong, Chang Hyung
Falvey, Cherie
Harris, Tamara B.
Simonsick, Eleanor M.
Satterfield, Suzanne
Ferrucci, Luigi
Metti, Andrea L.
Patel, Kushang V.
Yaffe, Kristine
TI Anemia and risk of dementia in older adults Findings from the Health ABC
study
SO NEUROLOGY
LA English
DT Article
ID ALZHEIMER-DISEASE; HEMOGLOBIN CONCENTRATION; CARDIOVASCULAR HEALTH;
COGNITIVE IMPAIRMENT; ERYTHROPOIETIN; MORTALITY; PREVALENCE; OUTCOMES;
DECLINE; COHORT
AB Objective: To determine whether anemia is associated with incident dementia in older adults.
Methods: We studied 2,552 older adults (mean age 76.1 years; 38.9% black; 51.8% female) participating in the Health, Aging, and Body Composition study and free of dementia at baseline. We defined anemia using WHO criteria (hemoglobin concentration <13 g/dL for men and <12 g/dL for women). Dementia diagnosis was determined by dementia medication use, hospital records, or a change in Modified Mini-Mental State (3MS) score of more than 1.5 SD from mean. Discrete time Cox proportional hazard regression models were used to examine the hazard for developing dementia associated with anemia.
Results: Of 2,552 participants, 392 (15.4%) older adults had anemia at baseline. Over 11 years of follow-up, 455 (17.8%) participants developed dementia. In the unadjusted model, those with baseline anemia had an increased risk of dementia (23% vs 17%, hazard ratio = 1.64; 95% confidence interval 1.30, 2.07) compared to those without anemia. The association remained significant after adjusting for demographics, APOE epsilon 4, baseline 3MS score, comorbidities, and renal function. Additional adjustment for other anemia measures (mean corpuscular volume, red cell distribution width), erythropoietin, and C-reactive protein did not appreciably change the results. There was no interaction by sex and race on risk of developing dementia.
Conclusion: Among older adults, anemia is associated with an increased risk of developing dementia. Findings suggest that further study of anemia as a risk factor for dementia and a target for intervention for cognitive health is warranted.
C1 [Hong, Chang Hyung] Ajou Univ Sch Med, Dept Psychiat, Suwon, South Korea.
[Hong, Chang Hyung] Ajou Univ Sch Med, Inst Aging, Suwon, South Korea.
[Falvey, Cherie; Yaffe, Kristine] Univ Calif San Francisco, Sch Med, Dept Psychiat, San Francisco, CA 94143 USA.
[Yaffe, Kristine] Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA USA.
[Yaffe, Kristine] Univ Calif San Francisco, Sch Med, Dept Neurol, San Francisco, CA USA.
[Falvey, Cherie; Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Baltimore, MD 21224 USA.
[Simonsick, Eleanor M.; Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
[Satterfield, Suzanne] Univ Tennessee Hlth Sci Ctr, Dept Prevent Med, Memphis, TN USA.
[Metti, Andrea L.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA.
[Patel, Kushang V.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA.
RP Yaffe, K (reprint author), Univ Calif San Francisco, Sch Med, Dept Psychiat, San Francisco, CA 94143 USA.
EM kristine.yaffe@ucsf.edu
FU NIA [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01-AG028050]; NINR
[R01-NR012459]; NIH; National Institute of Aging; National Institute of
Aging [K24AG031155]; American Health Assistance Foundation [A201-0029]
FX NIA contract numbers: N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106. NIA
grant numbers: R01-AG028050, NINR grant R01-NR012459. This research was
supported in part by the Intramural Research Program of the NIH and
National Institute of Aging. Dr. Yaffe is supported in part by a
National Institute of Aging Grant (K24AG031155) and a grant from the
American Health Assistance Foundation (A201-0029).
NR 34
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U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD AUG 6
PY 2013
VL 81
IS 6
BP 528
EP 533
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA 304JH
UT WOS:000330742400007
PM 23902706
ER
PT J
AU Blackler, AR
Morgan, NY
Gao, B
Olano, LR
Armani, MD
Romantseva, E
Kakareka, JW
Bonner, RF
Mukherjee, S
Xiao, B
Tran, K
Pohida, TJ
Emmert-Buck, MR
Tangrea, MA
Markey, SP
AF Blackler, A. R.
Morgan, N. Y.
Gao, B.
Olano, L. R.
Armani, M. D.
Romantseva, E.
Kakareka, J. W.
Bonner, R. F.
Mukherjee, S.
Xiao, B.
Tran, K.
Pohida, T. J.
Emmert-Buck, M. R.
Tangrea, M. A.
Markey, S. P.
TI Proteomic Analysis of Nuclei Dissected from Fixed Rat Brain Tissue Using
Expression Microdissection
SO ANALYTICAL CHEMISTRY
LA English
DT Article
ID LASER CAPTURE MICRODISSECTION; TANDEM MASS-SPECTROMETRY; PROMOTER
METHYLATION; STATISTICAL-MODEL; PROTEIN; CELLS; CANCER
AB Expression microdissection (xMD) is a high-throughput, operator-independent technology that enables the procurement of specific cell populations from tissue specimens. In this method, histological sections are first stained for cellular markers via either chemical or immuno-guided methods, placed in close contact with an ethylene vinyl acetate (EVA) film, and exposed to a light source. The focal, transient heating of the stained cells or subcellular structures melts the EVA film selectively to the targets for procurement. In this report, we introduce a custom-designed flashcube system that permits consistent and reproducible microdissection of nuclei across an FFPE rat brain tissue section in milliseconds. In addition, we present a method to efficiently recover and combine captured proteins from multiple xMD films. Both light and scanning electron microscopy demonstrated captured nuclear structures. Shotgun proteomic analysis of the samples showed a significant enrichment in nuclear localized proteins, with an average 25% of recovered proteins localized to the nucleus, versus 15% for whole tissue controls (p<0.001). Targeted mass spectrometry using multiple reaction monitoring (MRM) showed more impressive data, with a 3-fold enrichment in histones, and a concurrent depletion of proteins localized to the cytoplasm, cytoskeleton, and mitochondria. These data demonstrate that the flashcube-xMD technology is applicable to the proteomic study of a broad range of targets in molecular pathology.
C1 [Blackler, A. R.; Armani, M. D.; Mukherjee, S.; Emmert-Buck, M. R.; Tangrea, M. A.] NCI, NIH, Bethesda, MD 20892 USA.
[Morgan, N. Y.; Romantseva, E.] Natl Inst Biomed Imaging & Biomed Engn, NIH, Bethesda, MD 20892 USA.
[Gao, B.; Markey, S. P.] NIMH, NIH, Bethesda, MD 20892 USA.
[Olano, L. R.] NIAID, RTB, NIH, Bethesda, MD 20892 USA.
[Kakareka, J. W.; Xiao, B.; Pohida, T. J.] NIH, Ctr Informat Technol, Bethesda, MD 20892 USA.
[Bonner, R. F.; Tran, K.] NICHHD, NIH, Bethesda, MD 20892 USA.
RP Emmert-Buck, MR (reprint author), NCI, NIH, Bethesda, MD 20892 USA.
EM buckm@mail.nih.gov
OI Kakareka, John/0000-0003-0072-0035
FU NIH [ZIA MH002919, 1ZIABC010729]; Center for Cancer Research; NCI; NIBIB
FX This work was supported in part by the intramural program at the NIH
(Grants ZIA MH002919 and 1ZIABC010729), including the Center for Cancer
Research, NCI, NIBIB, and an NIH Directors award. Special thanks goes to
the NIAID Research Technologies Branch for sample analysis and
bioinformatics assistance. Thanks to Kris Ylaya and Qiang Du, M.D. for
tissue sectioning and to Jeff Hanson for assistance with the Arcturus XT
instrument. We benefitted from helpful technical discussions and
assistance from NIH scientists J. Lippincott-Schwartz, C. Ott, D.
Sackett, D. Johann, B. Martin, J. Kowalak, A. J. Makusky, M. Gucek, and
A. Aponte. The loan from Agilent of a 6490 triple quadrupole mass
spectrometer with chipcube and 1260 HPLC and autosampler stack
contributed to the successful MRM analyses and is gratefully
acknowledged.
NR 29
TC 4
Z9 4
U1 2
U2 11
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0003-2700
EI 1520-6882
J9 ANAL CHEM
JI Anal. Chem.
PD AUG 6
PY 2013
VL 85
IS 15
BP 7139
EP 7145
DI 10.1021/ac400691k
PG 7
WC Chemistry, Analytical
SC Chemistry
GA 199RW
UT WOS:000323014000025
PM 23799655
ER
PT J
AU Kaplan, BB
Kar, AN
Gioio, AE
Aschrafi, A
AF Kaplan, Barry B.
Kar, Amar N.
Gioio, Anthony E.
Aschrafi, Armaz
TI MicroRNAs in the axon and presynaptic nerve terminal
SO FRONTIERS IN CELLULAR NEUROSCIENCE
LA English
DT Review
DE axonal mRNAs; mitochondrial mRNAs; intra-axonal protein synthesis;
translational regulation; energy metabolism; ROS generation; axonal
growth
ID LOCAL PROTEIN-SYNTHESIS; SYMPATHETIC NEURONS; MESSENGER-RNA;
OXIDATIVE-PHOSPHORYLATION; CORTICAL-NEURONS; TRANSLATION; CYTOSKELETAL;
SYNAPSE; GROWTH; ROLES
AB The distal structural/functional domains of the neuron, to include the axon and presynaptic nerve terminal, contain a large, heterogeneous population of mRNAs and an active protein synthetic system. These local components of the genetic expression machinery play a critical role in the development, function, and long-term viability of the neuron. In addition to the local mRNA populations these presynaptic domains contain a significant number of non-coding RNAs that regulate gene expression post-transcriptionally. Here, we review a small, but rapidly evolving literature on the composition and function of microRNAs that regulate gene expression locally in the axon and nerve terminal. In this capacity, these small regulatory RNAs have a profound effect on axonal protein synthesis, local energy metabolism, and the modulation of axonal outgrowth and branching.
C1 [Kaplan, Barry B.; Kar, Amar N.; Gioio, Anthony E.] NIMH, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Aschrafi, Armaz] Radboud Univ Nijmegen, Ctr Med, Dept Cognit Neurosci, Donders Inst Brain Cognit & Behav, NL-6525 ED Nijmegen, Netherlands.
RP Kaplan, BB (reprint author), NIMH, Mol Biol Lab, NIH, 9000 Rockville Pike,Bldg 10,Room 4N213, Bethesda, MD 20892 USA.
EM barry.kaplan@nih.gov
OI Kar, Amar/0000-0003-2380-7504
FU Division of Intramural Research Programs of the National Institute of
Mental Health [ZO1MH00276]
FX The authors work was supported by the Division of Intramural Research
Programs of the National Institute of Mental Health (ZO1MH00276). We
thank Noreen Gervasi, Mi Hellifors, Margaret Macgibeny, Orlangie
Natera-Naranjo, and Sanah Vohra for invaluable contributions to the
authors' research endeavors.
NR 26
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U1 0
U2 4
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1662-5102
J9 FRONT CELL NEUROSCI
JI Front. Cell. Neurosci.
PD AUG 6
PY 2013
VL 7
AR 126
DI 10.3389/fncel.2013.00126
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 205BA
UT WOS:000323414200001
PM 23964201
ER
PT J
AU Weinstein, SJ
Virtamo, J
Albanes, D
AF Weinstein, S. J.
Virtamo, J.
Albanes, D.
TI Pigmentation-related phenotypes and risk of prostate cancer
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE prostate cancer; MC1R; vitamin D; hair colour; red hair; pigmentation
traits
ID ULTRAVIOLET-RADIATION; MELANOCORTIN-1 RECEPTOR; MC1R VARIANTS; SKIN
TYPE; RED HAIR; MELANOMA; ASSOCIATIONS; METAANALYSIS; CLONING; COLON
AB Background: Solar ultraviolet radiation exposure has been inversely related to prostate cancer incidence and mortality, possibly mediated through vitamin D status. Pigmentation-related traits influence endogenous vitamin D synthesis and may alter risk of prostate cancer.
Methods: We examined prostate cancer in relation to hair and eye colour, and skin phototype in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort. Incident cancer was diagnosed in 1982 out of 20 863 men. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from Cox proportional hazards models.
Results: Prostate cancer risk did not differ by eye colour or skin phototype. Men with naturally red hair were significantly less likely to develop prostate cancer (HR=0.46, 95% CI 0.24-0.89) than men with light brown hair (reference).
Conclusion: The red hair phenotype, which results from polymorphisms in the melanocortin-1-receptor (MC1R) gene, is associated with lower risk of prostate cancer. This pigmentation-related trait may influence prostate cancer development either directly, through genetic effects or regulatory mechanisms related to MC1R, another nearby gene, or other pigmentation genes, or indirectly, through associations with other exposures such as sunlight or vitamin D status.
C1 [Weinstein, S. J.; Albanes, D.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Virtamo, J.] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, FIN-00300 Helsinki, Finland.
RP Weinstein, SJ (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
EM weinstes@mail.nih.gov
RI Albanes, Demetrius/B-9749-2015
FU Intramural Research Program of the National Institutes of Health;
National Cancer Institute; US Public Health Service contracts from the
Department of Health and Human Services, National Cancer Institute
[N01-CN-45165, N01-RC-45035, N01-RC-37004, HHSN261201000006C]
FX This work was supported in part by the Intramural Research Program of
the National Institutes of Health and the National Cancer Institute. In
addition, this research was supported by the US Public Health Service
contracts N01-CN-45165, N01-RC-45035, N01-RC-37004, and
HHSN261201000006C from the Department of Health and Human Services,
National Cancer Institute.
NR 25
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U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
J9 BRIT J CANCER
JI Br. J. Cancer
PD AUG 6
PY 2013
VL 109
IS 3
BP 747
EP 750
DI 10.1038/bjc.2013.385
PG 4
WC Oncology
SC Oncology
GA 197CA
UT WOS:000322824700029
PM 23860522
ER
PT J
AU Arem, H
Gunter, MJ
Cross, AJ
Hollenbeck, AR
Sinha, R
AF Arem, H.
Gunter, M. J.
Cross, A. J.
Hollenbeck, A. R.
Sinha, R.
TI A prospective investigation of fish, meat and cooking-related
carcinogens with endometrial cancer incidence
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE endometrial cancer; meat; fish; meat mutagens; epidemiology
ID FOOD FREQUENCY QUESTIONNAIRE; NATIONWIDE CASE-CONTROL; DIETARY FACTORS;
UNITED-STATES; ANIMAL FOODS; RISK; CONSUMPTION; ASSOCIATION; SWEDEN;
HEALTH
AB Background: There are limited prospective studies of fish and meat intakes with risk of endometrial cancer and findings are inconsistent.
Methods: We studied associations between fish and meat intakes and endometrial cancer incidence in the large, prospective National Institutes of Health-AARP Diet and Health Study. Intakes of meat mutagens 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and benzo(a) pyrene (BaP) were also calculated. We used Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).
Results: We observed no associations with endometrial cancer risk comparing the highest to lowest intake quintiles of red (HR=0.91, 95% CI 0.77-1.08), white (0.98, 0.83-1.17), processed meats (1.02, 0.86-1.21) and fish (1.10, 95% CI 0.93-1.29). We also found no associations between meat mutagen intakes and endometrial cancer.
Conclusion: Our findings do not support an association between meat or fish intakes or meat mutagens and endometrial cancer.
C1 [Arem, H.; Cross, A. J.; Sinha, R.] Natl Canc Inst, Natl Inst Hlth, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
[Gunter, M. J.] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.
[Hollenbeck, A. R.] AARP, Washington, DC USA.
RP Arem, H (reprint author), Natl Canc Inst, Natl Inst Hlth, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
EM Aremhe2@mail.nih.gov
RI Sinha, Rashmi/G-7446-2015
OI Sinha, Rashmi/0000-0002-2466-7462
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute; Florida Department of Health; [T32 CA105666]
FX This work was supported in part by the pre-doctoral training grant T32
CA105666. This research was also supported in part by the Intramural
Research Program of the National Institutes of Health, National Cancer
Institute. Cancer incidence data from the Atlanta metropolitan area were
collected by the Georgia Center for Cancer Statistics, Department of
Epidemiology, Rollins School of Public Health, Emory University. Cancer
incidence data from California were collected by the California
Department of Health Services, Cancer Surveillance Section. Cancer
incidence data from the Detroit metropolitan area were collected by the
Michigan Cancer Surveillance Program, Community Health Administration,
State of Michigan. The Florida cancer incidence data used in this report
were collected by the Florida Cancer Data System under contract with the
Florida Department of Health. The views expressed herein are solely
those of the authors and do not necessarily reflect those of the
contractor or the Department of Health. Cancer incidence data from
Louisiana were collected by the Louisiana Tumor Registry, Louisiana
State University Medical Center in New Orleans. Cancer incidence data
from New Jersey were collected by the New Jersey State Cancer Registry,
Cancer Epidemiology Services, New Jersey State Department of Health and
Senior Services. Cancer incidence data from North Carolina were
collected by the North Carolina Central Cancer Registry. Cancer
incidence data from Pennsylvania were supplied by the Division of Health
Statistics and Research, Pennsylvania Department of Health, Harrisburg,
Pennsylvania. The Pennsylvania Department of Health specifically
disclaims responsibility for any analyses, interpretations or
conclusions. Cancer incidence data from Arizona were collected by the
Arizona Cancer Registry, Division of Public Health Services, Arizona
Department of Health Services. Cancer incidence data from Texas were
collected by the Texas Cancer Registry, Cancer Epidemiology and
Surveillance Branch, Texas Department of State Health Services. Cancer
incidence data from Nevada were collected by the Nevada Central Cancer
Registry, Center for Health Data and Research, Bureau of Health Planning
and Statistics, State Health Division, State of Nevada Department of
Health and Human Services. We also thank Sigurd Hermansen and Kerry
Grace Morrissey from Westat for study outcomes ascertainment and
management and Leslie Carroll at Information Management Services for
data support and analysis.
NR 29
TC 6
Z9 7
U1 0
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
J9 BRIT J CANCER
JI Br. J. Cancer
PD AUG 6
PY 2013
VL 109
IS 3
BP 756
EP 760
DI 10.1038/bjc.2013.252
PG 5
WC Oncology
SC Oncology
GA 197CA
UT WOS:000322824700031
PM 23695021
ER
PT J
AU Bodelon, C
Wentzensen, N
Schonfeld, SJ
Visvanathan, K
Hartge, P
Park, Y
Pfeiffer, RM
AF Bodelon, C.
Wentzensen, N.
Schonfeld, S. J.
Visvanathan, K.
Hartge, P.
Park, Y.
Pfeiffer, R. M.
TI Hormonal risk factors and invasive epithelial ovarian cancer risk by
parity
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE ovarian cancer; parity; nulliparity; risk factors; epidemiology
ID POSTMENOPAUSAL WOMEN; ORAL-CONTRACEPTIVES; ASSOCIATION; PREMENOPAUSAL;
DESIGN; BREAST
AB Background: Recent studies have suggested that several ovarian cancer risk factors differ by parity status, but these findings have not been confirmed. We evaluated whether known risk factors of ovarian cancer differ between nulliparous and parous women using data from two large prospective cohorts.
Methods: Data from the National Institutes of Health-AARP Diet and Health Study and the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial were combined for this analysis. Cox regression models were used to estimate associations with ovarian cancer risk. Risk heterogeneity by parity status was assessed using likelihood-ratio tests.
Results: Among the 125 437 women included in the analysis, there were 16 589 (13%) nulliparous women and 108 848 (87%) parous women. Of the 623 women diagnosed with invasive epithelial ovarian cancer, 102 (16%) were nulliparous and 521 (84%) were parous. While parity reduced ovarian cancer risk, no differences were found for other risk factors by parity. Among ever users of hormone therapy, body mass index suggestively increased the risk of ovarian cancer by 1.5-fold in nulliparous but not parous women (P-heterogeneity=0.08).
Conclusion: While nulliparous women have higher ovarian cancer risk than parous women, our findings suggest that the relative effects of most other risk factors do not differ by parity.
C1 [Bodelon, C.; Wentzensen, N.; Schonfeld, S. J.; Hartge, P.; Park, Y.; Pfeiffer, R. M.] Natl Canc Inst, NIH, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Schonfeld, S. J.] Int Agcy Res Canc, Sect Environm & Radiat, F-69372 Lyon, France.
[Visvanathan, K.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Visvanathan, K.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA.
RP Bodelon, C (reprint author), Natl Canc Inst, NIH, Div Canc Epidemiol & Genet, Rockville, MD USA.
EM clara.bodelon@nih.gov
OI Park, Yikyung/0000-0002-6281-489X
FU Intramural Research Program of the National Cancer Institute; Division
of Cancer Prevention, National Cancer Institute, NIH, DHHS; Florida
Department of Health, Tallahassee, Florida
FX This research was supported by the Intramural Research Program of the
National Cancer Institute and by contracts from the Division of Cancer
Prevention, National Cancer Institute, NIH, DHHS. PLCO: We thank the
Screening Center investigators and staff of 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. Most importantly, we acknowledge the PLCO study
participants for their contributions to making this study possible.
NIH-AARP: We are also indebted to the participants in the NIH-AARP Diet
and Health Study for their outstanding cooperation. We also thank Sigurd
Hermansen and Kerry Grace Morrissey from Westat for study outcomes
ascertainment and management and Leslie Carroll at Information
Management Services for data support and analysis. Cancer incidence data
from the Atlanta metropolitan area were collected by the Georgia Center
for Cancer Statistics, Department of Epidemiology, Rollins School of
Public Health, Emory University, Atlanta, Georgia. Cancer incidence data
from California were collected by the California Cancer Registry,
California Department of Public Health's Cancer Surveillance and
Research Branch, Sacramento, California. Cancer incidence data from the
Detroit metropolitan area were collected by the Michigan Cancer
Surveillance Program, Community Health Administration, Lansing,
Michigan. The Florida cancer incidence data used in this report were
collected by the Florida Cancer Data System (Miami, Florida) under
contract with the Florida Department of Health, Tallahassee, Florida.
The views expressed herein are solely those of the authors and do not
necessarily reflect those of the FCDC or FDOH. Cancer incidence data
from Louisiana were collected by the Louisiana Tumor Registry, Louisiana
State University Health Sciences Center School of Public Health, New
Orleans, Louisiana. Cancer incidence data from New Jersey were collected
by the New Jersey State Cancer Registry, Cancer Epidemiology Services,
New Jersey State Department of Health, Trenton, New Jersey. Cancer
incidence data from North Carolina were collected by the North Carolina
Central Cancer Registry, Raleigh, North Carolina. Cancer incidence data
from Pennsylvania were supplied by the Division of Health Statistics and
Research, Pennsylvania Department of Health, Harrisburg, Pennsylvania.
The Pennsylvania Department of Health specifically disclaims
responsibility for any analyses, interpretations or conclusions. Cancer
incidence data from Arizona were collected by the Arizona Cancer
Registry, Division of Public Health Services, Arizona Department of
Health Services, Phoenix, Arizona. Cancer incidence data from Texas were
collected by the Texas Cancer Registry, Cancer Epidemiology and
Surveillance Branch, Texas Department of State Health Services, Austin,
Texas. Cancer incidence data from Nevada were collected by the Nevada
Central Cancer Registry, State Health Division, State of Nevada
Department of Health and Human Services, Las Vegas, Nevada.
NR 22
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U1 3
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
J9 BRIT J CANCER
JI Br. J. Cancer
PD AUG 6
PY 2013
VL 109
IS 3
BP 769
EP 776
DI 10.1038/bjc.2013.344
PG 8
WC Oncology
SC Oncology
GA 197CA
UT WOS:000322824700033
PM 23820255
ER
PT J
AU Amburgey, K
Bailey, A
Hwang, JH
Tarnopolsky, MA
Bonnemann, CG
Medne, L
Mathews, KD
Collins, J
Daube, JR
Wellman, GP
Callaghan, B
Clarke, NF
Dowling, JJ
AF Amburgey, Kimberly
Bailey, Angela
Hwang, Jean H.
Tarnopolsky, Mark A.
Bonnemann, Carsten G.
Medne, Livija
Mathews, Katherine D.
Collins, James
Daube, Jasper R.
Wellman, Gregory P.
Callaghan, Brian
Clarke, Nigel F.
Dowling, James J.
TI Genotype-phenotype correlations in recessive RYR1-related myopathies
SO ORPHANET JOURNAL OF RARE DISEASES
LA English
DT Article
DE Genotype-phenotype relationships; RYR1; Congenital myopathies
ID CENTRAL CORE DISEASE; MULTI-MINICORE DISEASE; MUSCLE RYANODINE RECEPTOR;
CA2+ RELEASE CHANNEL; RYR1 MUTATIONS; MALIGNANT HYPERTHERMIA; CONGENITAL
MYOPATHIES; 1 GENE; COMMON-CAUSE; IDENTIFICATION
AB Background: RYR1 mutations are typically associated with core myopathies and are the most common overall cause of congenital myopathy. Dominant mutations are most often associated with central core disease and malignant hyperthermia, and genotype-phenotype patterns have emerged from the study of these mutations that have contributed to the understanding of disease pathogenesis. The recent availability of genetic testing for the entire RYR1 coding sequence has led to a dramatic expansion in the identification of recessive mutations in core myopathies and other congenital myopathies. To date, no clear patterns have been identified in these recessive mutations, though no systematic examination has yet been performed.
Methods: In this study, we investigated genotype-phenotype correlations in a large combined cohort of unpublished (n = 14) and previously reported (n = 92) recessive RYR1 cases.
Results: Overall examination of this cohort revealed nearly 50% of cases to be non-core myopathy related. Our most significant finding was that hypomorphic mutations (mutations expected to diminish RyR1 expression) were enriched in patients with severe clinical phenotypes. We also determined that hypomorphic mutations were more likely to be encountered in non-central core myopathies. With analysis of the location of non-hypomorphic mutations, we found that missense mutations were generally enriched in the MH/CCD hotspots and specifically enriched in the selectivity filter of the channel pore.
Conclusions: These results support a hypothesis that loss of protein function is a key predictive disease parameter. In addition, they suggest that decreased RyR1 expression may dictate non-core related pathology though, data on protein expression was limited and should be confirmed in a larger cohort. Lastly, the results implicate abnormal ion conductance through the channel pore in the pathogenesis in recessive core myopathies. Overall, our findings represent a comprehensive analysis of genotype-phenotype associations in recessive RYR1-myopathies.
C1 [Amburgey, Kimberly; Bailey, Angela; Dowling, James J.] Univ Michigan, Ctr Med, Dept Pediat, Taubman Med Res Inst, Ann Arbor, MI 48109 USA.
[Hwang, Jean H.; Clarke, Nigel F.] Univ Sydney, Childrens Hosp Westmead, Inst Neurosci & Muscle Res, Sydney, NSW 2145, Australia.
[Tarnopolsky, Mark A.] McMaster Univ, Med Ctr, Dept Neuromuscular & Neurometabol Dis, Hamilton, ON, Canada.
[Bonnemann, Carsten G.] NIH, Neuromuscular & Neurogenet Disorders Childhood Se, Bethesda, MD 20892 USA.
[Medne, Livija] Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19104 USA.
[Mathews, Katherine D.] Univ Iowa, Dept Pediat, Carver Coll Med, Iowa City, IA 52242 USA.
[Mathews, Katherine D.] Univ Iowa, Dept Neurol, Carver Coll Med, Iowa City, IA 52242 USA.
[Collins, James] Cincinnati Childrens Hosp Med Ctr, Dept Pediat Neurol, Cincinnati, OH 45229 USA.
[Daube, Jasper R.] Mayo Fdn Med Educ & Res, Dept Neurol, Rochester, MN USA.
[Wellman, Gregory P.] Delta Pathol Grp, Shreveport, LA USA.
[Callaghan, Brian] Univ Michigan, Med Ctr, Dept Neurol, Ann Arbor, MI 48109 USA.
[Clarke, Nigel F.] Univ Sydney, Discipline Paediat & Child Hlth, Sydney, NSW 2145, Australia.
RP Clarke, NF (reprint author), Univ Sydney, Childrens Hosp Westmead, Inst Neurosci & Muscle Res, Level 3,Res Bldg Locked Bag 4001, Sydney, NSW 2145, Australia.
EM nigel.clarke@health.nsw.gov.au; jamedowl@med.umich.edu
OI Bailey, Angela/0000-0002-3757-6754
FU NIH [K08AR054835]; National Health & Medical Research Council [1035828,
1022707]; Albert Einstein College of Medicine; Taubman Research
Institute
FX This work has been supported by a grant from the NIH (K08AR054835 to
JJD) and the National Health & Medical Research Council (NC; grants
1035828 & 1022707). JH is also supported by the Albert Einstein College
of Medicine Senior Research Fellowship. Additional support comes from
the Taubman Research Institute Emerging Scholar fund. We thank Liz
Barnes from the NHMRC Clinical Trials Centre at University of Sydney for
the statistical analysis.
NR 44
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U1 0
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1750-1172
J9 ORPHANET J RARE DIS
JI Orphanet J. Rare Dis.
PD AUG 6
PY 2013
VL 8
AR 117
DI 10.1186/1750-1172-8-117
PG 12
WC Genetics & Heredity; Medicine, Research & Experimental
SC Genetics & Heredity; Research & Experimental Medicine
GA 201GX
UT WOS:000323129800001
PM 23919265
ER
PT J
AU Zhang, R
Jha, BK
Ogden, KM
Dong, BH
Zhao, L
Elliott, R
Patton, JT
Silverman, RH
Weiss, SR
AF Zhang, Rong
Jha, Babal K.
Ogden, Kristen M.
Dong, Beihua
Zhao, Ling
Elliott, Ruth
Patton, John T.
Silverman, Robert H.
Weiss, Susan R.
TI Homologous 2 ',5 '-phosphodiesterases from disparate RNA viruses
antagonize antiviral innate immunity
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE Reoviridae; Nidovirales; RNA capping enzyme; interferon-stiumulated gene
ID MOUSE HEPATITIS-VIRUS; ROTAVIRUS OPEN CORES; MURINE CORONAVIRUS;
2',5'-OLIGOADENYLATE SYNTHETASE; 2-5A-DEPENDENT RNASE; PROSTATE-CANCER;
INFECTED-CELLS; STRAIN A59; INTERFERON; PROTEIN
AB Efficient and productive virus infection often requires viral countermeasures that block innate immunity. The IFN-inducible 2',5'-oligoadenylate (2-5A) synthetases (OASs) and ribonuclease (RNase) L are components of a potent host antiviral pathway. We previously showed that murine coronavirus (MHV) accessory protein ns2, a 2H phosphoesterase superfamily member, is a phosphodiesterase (PDE) that cleaves 2-5A, thereby preventing activation of RNase L. The PDE activity of ns2 is required for MHV replication in macrophages and for hepatitis. Here, we show that group A rotavirus (RVA), an important cause of acute gastroenteritis in children worldwide, encodes a similar PDE. The RVA PDE forms the carboxy-terminal domain of the minor core protein VP3 (VP3-CTD) and shares sequence and predicted structural homology with ns2, including two catalytic HxT/S motifs. Bacterially expressed VP3-CTD exhibited 2',5'-PDE activity, which cleaved 2-5A in vitro. In addition, VP3-CTD expressed transiently in mammalian cells depleted 2-5A levels induced by OAS activation with poly (rI):poly(rC), preventing RNase L activation. In the context of recombinant chimeric MHV expressing inactive ns2, VP3-CTD restored the ability of the virus to replicate efficiently in macrophages or in the livers of infected mice, whereas mutant viruses expressing inactive VP3-CTD (H718A or H798R) were attenuated. In addition, chimeric viruses expressing either active ns2 or VP3-CTD, but not nonfunctional equivalents, were able to protect ribosomal RNA from RNase L-mediated degradation. Thus, VP3-CTD is a 2',5'-PDE able to functionally substitute for ns2 in MHV infection. Remarkably, therefore, two disparate RNA viruses encode proteins with homologous 2',5'-PDEs that antagonize activation of innate immunity.
C1 [Zhang, Rong; Zhao, Ling; Elliott, Ruth; Weiss, Susan R.] Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA.
[Zhang, Rong] Chinese Acad Agr Sci, Shanghai Vet Res Inst, Dept Swine Infect Dis, Shanghai 200241, Peoples R China.
[Jha, Babal K.; Dong, Beihua; Silverman, Robert H.] Cleveland Clin, Lerner Res Inst, Dept Canc Biol, Cleveland, OH 44195 USA.
[Ogden, Kristen M.; Patton, John T.] NIAID, Rotavirus Mol Biol Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Weiss, SR (reprint author), Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA.
EM SILVERR@ccf.org; weisssr@mail.med.upenn.edu
RI Patton, John/P-1390-2014;
OI Jha, Babal/0000-0002-7660-5255
FU National Institutes of Health [RO1-AI104887, R56-AI-095285]; Intramural
Research Program of the National Institute of Allergy and Infectious
Diseases, National Institutes of Health; China Scholarship council
FX We thank Sasha Stone and L. Dillon Birdwell for technical help. This
work was supported by National Institutes of Health Grants RO1-AI104887
(to S.R.W. and R.H.S.) and R56-AI-095285 (to S.R.W.) and the Intramural
Research Program of the National Institute of Allergy and Infectious
Diseases, National Institutes of Health (J.T.P. and K.M.O.). R.Z. was
supported in part by the China Scholarship council.
NR 45
TC 41
Z9 42
U1 0
U2 7
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD AUG 6
PY 2013
VL 110
IS 32
BP 13114
EP 13119
DI 10.1073/pnas.1306917110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 196JQ
UT WOS:000322771100064
PM 23878220
ER
PT J
AU Belgard, TG
Montiel, JF
Wang, WZ
Garcia-Moreno, F
Margulies, EH
Ponting, CP
Molnar, Z
AF Belgard, T. Grant
Montiel, Juan F.
Wang, Wei Zhi
Garcia-Moreno, Fernando
Margulies, Elliott H.
Ponting, Chris P.
Molnar, Zoltan
TI Adult pallium transcriptomes surprise in not reflecting predicted
homologies across diverse chicken and mouse pallial sectors
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE cerebral cortex; Wulst; equivalent circuit hypothesis; brain evolution;
dorsal ventricular ridge
ID EVOLUTION; NEOCORTEX; BRAIN; EXPRESSION; ORIGINS; CORTEX; TELENCEPHALON;
AMNIOTES; PATTERNS
AB The thorniest problem in comparative neurobiology is the identification of the particular brain region of birds and reptiles that corresponds to the mammalian neocortex [Butler AB, Reiner A, Karten HJ (2011) Ann N Y Acad Sci 1225:14-27; Wang Y, Brzozowska-Prechtl A, Karten HJ (2010) Proc Natl Acad Sci USA 107(28):12676-12681]. We explored which genes are actively transcribed in the regions of controversial ancestry in a representative bird (chicken) and mammal (mouse) at adult stages. We conducted four analyses comparing the expression patterns of their 5,130 most highly expressed one-to-one orthologous genes that considered global patterns of expression specificity, strong gene markers, and coexpression networks. Our study demonstrates transcriptomic divergence, plausible convergence, and, in two exceptional cases, conservation between specialized avian and mammalian telencephalic regions. This large-scale study potentially resolves the complex relationship between developmental homology and functional characteristics on the molecular level and settles long-standing evolutionary debates.
C1 [Belgard, T. Grant; Ponting, Chris P.] Univ Oxford, MRC, Funct Genom Unit, Dept Physiol Anat & Genet, Oxford OX1 3PT, England.
[Belgard, T. Grant; Margulies, Elliott H.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Montiel, Juan F.; Wang, Wei Zhi; Garcia-Moreno, Fernando; Molnar, Zoltan] Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 3QX, England.
[Montiel, Juan F.] Univ Diego Portales, Fac Med, Ctr Biomed Res, Santiago 8370068, Chile.
RP Molnar, Z (reprint author), Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 3QX, England.
EM grant@grantbelgard.com; chris.ponting@dpag.ox.ac.uk;
zoltan.molnar@dpag.ox.ac.uk
OI Montiel, Juan F/0000-0001-8919-4662; Molnar, Zoltan/0000-0002-6852-6004;
Belgard, Tildon/0000-0002-6962-7894; Ponting, Chris/0000-0003-0202-7816;
Garcia-Moreno, Fernando/0000-0001-9048-4237
FU Intramural Program of the National Human Genome Research Institute;
Medical Research Council; Biotechnology and Biological Sciences Research
Council; Human Frontiers Science Program postdoctoral fellowship;
Parkinson's UK; European Research Council; Marshall Scholarship, New
College, Oxford; NIH-Oxford-Cambridge Scholars Program; Becas Chile
Postdoctoral Fellowship
FX We thank E. D. Green and R. A. Chodroff for their roles in project
conceptualization, T. M. Sirey and L. Bluy for RNA extractions, H. Ozel
Abaan for the chicken poly(A) selection, the National Institutes of
Health (NIH) Intramural Sequencing Center for library preparation and
sequencing, J. L. Becker and M. W. Lesko for maintaining computational
infrastructure, L. Goodstadt for ruffus, L. Puelles and C. Nellaker for
helpful discussions, H. Kaune and A. F. P. Cheung for help in chicken
brain collection, and M. Neubrandt for help in brain sectioning. This
work was supported by the Intramural Program of the National Human
Genome Research Institute, the Medical Research Council, Biotechnology
and Biological Sciences Research Council, a Human Frontiers Science
Program postdoctoral fellowship, Parkinson's UK, the European Research
Council, the Marshall Scholarship, New College, Oxford, the
NIH-Oxford-Cambridge Scholars Program, and the Becas Chile Postdoctoral
Fellowship.
NR 23
TC 28
Z9 28
U1 0
U2 11
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 AUG 6
PY 2013
VL 110
IS 32
BP 13150
EP 13155
DI 10.1073/pnas.1307444110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 196JQ
UT WOS:000322771100070
PM 23878249
ER
PT J
AU Dimitrov, EL
Kuo, J
Kohno, K
Usdin, TB
AF Dimitrov, Eugene L.
Kuo, Jonathan
Kohno, Kenji
Usdin, Ted B.
TI Neuropathic and inflammatory pain are modulated by tuberoinfundibular
peptide of 39 residues
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE supraspinal pain; allodynia; partial sciatic nerve ligation; Freund's
adjuvant
ID LOCUS-COERULEUS NEURONS; PERIPHERAL-NERVE INJURY; RAT SPINAL-CORD;
PARATHYROID-HORMONE-2 RECEPTOR; LENTIVIRAL VECTORS; CERULEUS NEURONS;
CELL GROUPS; AMITRIPTYLINE; NOCICEPTION; PROJECTIONS
AB Nociceptive information is modulated by a large number of endogenous signaling agents that change over the course of recovery from injury. This plasticity makes understanding regulatory mechanisms involved in descending inhibition of pain scientifically and clinically important. Neurons that synthesize the neuropeptide TIP39 project to many areas that modulate nociceptive information. These areas are enriched in its receptor, the parathyroid hormone 2 receptor (PTH2R). We previously found that TIP39 affects several acute nociceptive responses, leading us to now investigate its potential role in chronic pain. Following nerve injury, both PTH2R and TIP39 knockout mice developed less tactile and thermal hypersensitivity than controls and returned to baseline sensory thresholds faster. Effects of hindpaw inflammatory injury were similarly decreased in knockout mice. Blockade of alpha-2 adrenergic receptors increased the tactile and thermal sensitivity of apparently recovered knockout mice, returning it to levels of neuropathic controls. Mice with locus coeruleus (LC) area injection of lentivirus encoding a secreted PTH2R antagonist had a rapid, alpha-2 reversible, apparent recovery from neuropathic injury similar to the knockout mice. Ablation of LC area glutamatergic neurons led to local PTH2R-ir loss, and barley lectin was transferred from local glutamatergic neurons to GABA interneurons that surround the LC. These results suggest that TIP39 signaling modulates sensory thresholds via effects on glutamatergic transmission to brain-stem GABAergic interneurons that innervate noradrenergic neurons. TIP39's normal role may be to inhibit release of hypoalgesic amounts of norepinephrine during chronic pain. The neuropeptide may help maintain central sensitization, which could serve to enhance guarding behavior.
C1 [Dimitrov, Eugene L.; Kuo, Jonathan; Usdin, Ted B.] NIMH, Sect Fundamental Neurosci, Bethesda, MD 20892 USA.
[Kohno, Kenji] Nara Inst Sci & Technol, Grad Sch Biol Sci, Lab Mol & Cell Genet, Ikoma Nara 6300192, Japan.
RP Usdin, TB (reprint author), NIMH, Sect Fundamental Neurosci, Bethesda, MD 20892 USA.
EM usdint@mail.nih.gov
FU National Institute of Meantal Health Intramural Research Program
FX Technical support was provided by Milan Rusnak. Support was provided by
the National Institute of Meantal Health Intramural Research Program.
NR 44
TC 6
Z9 6
U1 2
U2 12
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD AUG 6
PY 2013
VL 110
IS 32
BP 13156
EP 13161
DI 10.1073/pnas.1306342110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 196JQ
UT WOS:000322771100071
PM 23878240
ER
PT J
AU Hinck, AP
Huang, T
AF Hinck, Andrew P.
Huang, Tao
TI TGF-beta Antagonists: Same Knot, but Different Hold
SO STRUCTURE
LA English
DT Editorial Material
ID INSIGHTS
C1 [Hinck, Andrew P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA.
[Huang, Tao] NCI, Struct Biophys Lab, Frederick, MD 21702 USA.
RP Hinck, AP (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA.
EM hinck@uthscsa.edu
FU NCI NIH HHS [P30 CA054174, R01 CA172886]; NIGMS NIH HHS [R01 GM058670]
NR 10
TC 3
Z9 3
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0969-2126
J9 STRUCTURE
JI Structure
PD AUG 6
PY 2013
VL 21
IS 8
BP 1269
EP 1270
DI 10.1016/j.str.2013.07.015
PG 2
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 198MV
UT WOS:000322927900003
PM 23931139
ER
PT J
AU Nemecek, D
Boura, E
Wu, WM
Cheng, NQ
Plevka, P
Qiao, J
Mindich, L
Heymann, JB
Hurley, JH
Steven, AC
AF Nemecek, Daniel
Boura, Evzen
Wu, Weimin
Cheng, Naiqian
Plevka, Pavel
Qiao, Jian
Mindich, Leonard
Heymann, J. Bernard
Hurley, James H.
Steven, Alasdair C.
TI Subunit Folds and Maturation Pathway of a dsRNA Virus Capsid
SO STRUCTURE
LA English
DT Article
ID RNA BACTERIOPHAGE PHI-6; MINUS-STRAND SYNTHESIS; CRYOELECTRON
MICROSCOPY; ANGSTROM RESOLUTION; ATOMIC-STRUCTURE; BINDING-SITES; UCSF
CHIMERA; PROTEIN P7; MECHANISM; VISUALIZATION
AB The cystovirus phi 6 shares several distinct features with other double-stranded RNA (dsRNA) viruses, including the human pathogen, rotavirus: segmented genomes, nonequivalent packing of 120 subunits in its icosahedral capsid, and capsids as compartments for transcription and replication. phi 6 assembles as a dodecahedral procapsid that undergoes major conformational changes as it matures into the spherical capsid. We determined the crystal structure of the capsid protein, P1, revealing a flattened trapezoid subunit with an alpha-helical fold. We also solved the procapsid with cryo-electron microscopy to comparable resolution. Fitting the crystal structure into the procapsid disclosed substantial conformational differences between the two P1 conformers. Maturation via two intermediate states involves remodeling on a similar scale, besides huge rigid-body rotations. The capsid structure and its stepwise maturation that is coupled to sequential packaging of three RNA segments sets the cystoviruses apart from other dsRNA viruses as a dynamic molecular machine.
C1 [Nemecek, Daniel; Wu, Weimin; Cheng, Naiqian; Heymann, J. Bernard; Steven, Alasdair C.] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Boura, Evzen; Hurley, James H.] Natl Inst Diabet & Digest & Kidney Dis, NIH, Bethesda, MD 20892 USA.
[Nemecek, Daniel; Plevka, Pavel] Masaryk Univ, Cent European Inst Technol, Brno 62500, Czech Republic.
[Boura, Evzen] Inst Organ Chem & Biochem AS CR, Vvi, Prague 16600 6, Czech Republic.
[Plevka, Pavel] Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA.
[Qiao, Jian; Mindich, Leonard] Univ Med & Dent New Jersey, Publ Hlth Res Inst Ctr, Dept Microbiol, Newark, NJ 07103 USA.
RP Steven, AC (reprint author), NIAMSD, NIH, 50 South Dr, Bethesda, MD 20892 USA.
EM stevena@mail.nih.gov
RI Boura, Evzen/G-5275-2014; Plevka, Pavel/H-8661-2014;
OI Plevka, Pavel/0000-0003-4215-3315; Heymann, Bernard/0000-0002-8872-5326
FU NIAMS; NIDDK; IATAP grants; ASCR (RVO) [61388963]; US Department of
Energy, Office of Science, Office of Basic Energy Sciences
[W-31-109-Eng-38]
FX This work was supported by the intramural research programs of NIAMS and
NIDDK and by IATAP grants (to J.H.H. for E.B. and to A.C.S.) and by ASCR
(RVO: 61388963 to E.B.). Crystallographic data were collected at the
Southeast Regional Collaborative Access Team 22-ID beamline at the
Advanced Photon Source, Argonne National Laboratory. Use of the Advanced
Photon Source was supported by the US Department of Energy, Office of
Science, Office of Basic Energy Sciences, under contract
W-31-109-Eng-38.
NR 51
TC 20
Z9 20
U1 1
U2 15
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0969-2126
J9 STRUCTURE
JI Structure
PD AUG 6
PY 2013
VL 21
IS 8
BP 1374
EP 1383
DI 10.1016/j.str.2013.06.007
PG 10
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 198MV
UT WOS:000322927900013
PM 23891288
ER
PT J
AU Prasad, V
AF Prasad, Vinay
TI Taking care of sick patients
SO CANADIAN MEDICAL ASSOCIATION JOURNAL
LA English
DT Editorial Material
C1 NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Prasad, V (reprint author), NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CMA-CANADIAN MEDICAL ASSOC
PI OTTAWA
PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 5W8, CANADA
SN 0820-3946
EI 1488-2329
J9 CAN MED ASSOC J
JI Can. Med. Assoc. J.
PD AUG 6
PY 2013
VL 185
IS 11
BP 1008
EP 1008
DI 10.1503/cmaj.130047
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 196ZR
UT WOS:000322816700037
PM 23877668
ER
PT J
AU Anderson, ARA
Tomlin, CJ
Couch, J
Gallahan, D
AF Anderson, Alexander R. A.
Tomlin, Claire J.
Couch, Jennifer
Gallahan, Dan
TI Mathematics of the Integrative Cancer Biology Program
SO INTERFACE FOCUS
LA English
DT Editorial Material
DE mathematical oncology; National Cancer Institute; Integrative Cancer
Biology Program
C1 [Anderson, Alexander R. A.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA.
[Tomlin, Claire J.] Univ Calif Berkeley, Dept Elect Engn & Comp Sci, Berkeley, CA 94720 USA.
[Couch, Jennifer; Gallahan, Dan] NCI, Div Canc Biol, Rockville, MD 20850 USA.
RP Anderson, ARA (reprint author), Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA.
EM alexander.anderson@moffitt.org
RI Anderson, Alexander/A-2713-2011
OI Anderson, Alexander/0000-0002-2536-4383
NR 13
TC 1
Z9 1
U1 0
U2 10
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 2042-8898
J9 INTERFACE FOCUS
JI Interface Focus
PD AUG 6
PY 2013
VL 3
IS 4
SI SI
DI 10.1098/rsfs.2013.0023
PG 3
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 170MA
UT WOS:000320853900011
ER
PT J
AU Tao-Cheng, JH
Yang, Y
Bayer, KU
Reese, TS
Dosemeci, A
AF Tao-Cheng, J-H.
Yang, Y.
Bayer, K. U.
Reese, T. S.
Dosemeci, A.
TI EFFECTS OF CaMKII INHIBITOR TATCN21 ON ACTIVITY-DEPENDENT REDISTRIBUTION
OF CaMKII IN HIPPOCAMPAL NEURONS
SO NEUROSCIENCE
LA English
DT Article
DE synapse; CaMKII inhibitor; tatCN21; polyribosomes; electron microscopy;
PSD
ID PROTEIN-KINASE-II; POSTSYNAPTIC DENSITY; CA-2+ CALMODULIN;
MESSENGER-RNAS; FEAR MEMORY; RAT-BRAIN; SYNAPSES; STORAGE; SPINES
AB TatCN21 is a membrane permeable calcium/calmodulin-dependent protein kinase II (CaMKII) inhibitor derived from the inhibitor protein CaMKIIN. TatCN21 has been used to demonstrate the involvement of CaMKII in a variety of physiological and pathological phenomena, and it also limits excitotoxic damage in neurons. Here we use preembedding immunogold electron microscopy to examine the effect of tatCN21 on the redistribution of CaMKII in cultured hippocampal neurons. Incubation of cultures with tatCN21 (20 mu M for 20 min) prior to exposure to N-methyl-oasparic acid (NMDA) (50 mu M for 2 min) inhibited both the accumulation of CaMKII at postsynaptic densities (PSDs) and CaMKII clustering in the dendrites. Under these conditions, CaMKII also formed morphologically distinct aggregates with polyribosomes near the PSD and in dendrites. Formation of these CaMKII-polyribosome aggregates requires the presence of both tatCN21 and calcium, and was augmented upon exposure to high K+ or NMDA. CaMKII-polyribosome aggregates formed consistently with 20 mu M tatCN21, but minimally or not at all with 5 mu M. However, these aggregates are not induced by another CaMKII inhibitor, KN93. Formation of CaMKII-polyribosome aggregates was completely reversible within 1 h after washout of tatCN21. Effects of tatCN21 were largely restricted to dendrites, with minimal effect in the soma. The effects of tatCN21 on CaMKII distribution can be used to dissect the mechanism of CaMKII involvement in cellular events. Published by Elsevier Ltd. on behalf of IBRO.
C1 [Tao-Cheng, J-H.] NINDS, EM Facil, NIH, Bethesda, MD 20892 USA.
[Yang, Y.; Reese, T. S.; Dosemeci, A.] NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA.
[Bayer, K. U.] Univ Colorado Denver, Dept Pharmacol, Sch Med, Aurora, CO USA.
RP Tao-Cheng, JH (reprint author), 49 Convent Dr,Room 3A50, Bethesda, MD 20892 USA.
EM chengs@ninds.nih.gov
FU NIH, NINDS; [R01NS052644]
FX We thank Christine A. Winters for hippocampal neuronal cultures,
Virginia Crocker and Rita Azzam for expert EM technical support, and Dr.
Paul Gallant for helpful discussions and the perfusion-fixed brain in
Fig. 3D. Supported by the Intramural Research Program of the NIH, NINDS,
and by R01NS052644 (to K.U.B.).
NR 26
TC 8
Z9 8
U1 0
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4522
J9 NEUROSCIENCE
JI Neuroscience
PD AUG 6
PY 2013
VL 244
BP 188
EP 196
DI 10.1016/j.neuroscience.2013.03.063
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 163OW
UT WOS:000320347800016
PM 23583761
ER
PT J
AU Dickey, JS
Gonzalez, Y
Aryal, B
Mog, S
Nakamura, AJ
Redon, CE
Baxa, U
Rosen, E
Cheng, G
Zielonka, J
Parekh, P
Mason, KP
Joseph, J
Kalyanaraman, B
Bonner, W
Herman, E
Shacter, E
Rao, VA
AF Dickey, Jennifer S.
Gonzalez, Yanira
Aryal, Baikuntha
Mog, Steven
Nakamura, Asako J.
Redon, Christophe E.
Baxa, Ulrich
Rosen, Elliot
Cheng, Gang
Zielonka, Jacek
Parekh, Palak
Mason, Karen P.
Joseph, Joy
Kalyanaraman, Balaraman
Bonner, William
Herman, Eugene
Shacter, Emily
Rao, V. Ashutosh
TI Mito-Tempol and Dexrazoxane Exhibit Cardioprotective and
Chemotherapeutic Effects through Specific Protein Oxidation and
Autophagy in a Syngeneic Breast Tumor Preclinical Model
SO PLOS ONE
LA English
DT Article
ID RAT MAMMARY-CARCINOMA; ANTHRACYCLINE-INDUCED CARDIOTOXICITY; CARDIAC
TROPONIN-T; CELL CLONES; INTERCELLULAR COMMUNICATION; ANTIOXIDANT
PROPERTIES; METASTATIC CAPACITY; GROWTH-INHIBITION; SERUM-ALBUMIN;
DNA-DAMAGE
AB Several front-line chemotherapeutics cause mitochondria-derived, oxidative stress-mediated cardiotoxicity. Iron chelators and other antioxidants have not completely succeeded in mitigating this effect. One hindrance to the development of cardioprotectants is the lack of physiologically-relevant animal models to simultaneously study antitumor activity and cardioprotection. Therefore, we optimized a syngeneic rat model and examined the mechanisms by which oxidative stress affects outcome. Immune-competent spontaneously hypertensive rats (SHRs) were implanted with passaged, SHR-derived, breast tumor cell line, SST-2. Tumor growth and cytokine responses (IL-1A, MCP-1, TNF-alpha) were observed for two weeks post-implantation. To demonstrate the utility of the SHR/SST-2 model for monitoring both anticancer efficacy and cardiotoxicity, we tested cardiotoxic doxorubicin alone and in combination with an established cardioprotectant, dexrazoxane, or a nitroxide conjugated to a triphenylphosphonium cation, Mito-Tempol (4) [Mito-T (4)]. As predicted, tumor reduction and cardiomyopathy were demonstrated by doxorubicin. We confirmed mitochondrial accumulation of Mito-T (4) in tumor and cardiac tissue. Dexrazoxane and Mito-T (4) ameliorated doxorubicin-induced cardiomyopathy without altering the antitumor activity. Both agents increased the pro-survival autophagy marker LC3-II and decreased the apoptosis marker caspase-3 in the heart, independently and in combination with doxorubicin. Histopathology and transmission electron microscopy demonstrated apoptosis, autophagy, and necrosis corresponding to cytotoxicity in the tumor and cardioprotection in the heart. Changes in serum levels of 8-oxo-dG-modified DNA and total protein carbonylation corresponded to cardioprotective activity. Finally, 2D-electrophoresis/mass spectrometry identified specific serum proteins oxidized under cardiotoxic conditions. Our results demonstrate the utility of the SHR/SST-2 model and the potential of mitochondrially-directed agents to mitigate oxidative stress-induced cardiotoxicity. Our findings also emphasize the novel role of specific protein oxidation markers and autophagic mechanisms for cardioprotection.
C1 [Dickey, Jennifer S.; Gonzalez, Yanira; Aryal, Baikuntha; Rosen, Elliot; Mason, Karen P.; Shacter, Emily; Rao, V. Ashutosh] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA.
[Mog, Steven] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA.
[Nakamura, Asako J.; Redon, Christophe E.; Parekh, Palak; Bonner, William] NCI, Mol Pharmacol Lab, Bethesda, MD 20892 USA.
[Baxa, Ulrich] Frederick Natl Lab Canc Res, Electron Microscopy Lab, Adv Technol Program, Frederick, MD USA.
[Cheng, Gang; Zielonka, Jacek; Joseph, Joy; Kalyanaraman, Balaraman] Med Coll Wisconsin, Dept Biophys, Milwaukee, WI 53226 USA.
[Cheng, Gang; Zielonka, Jacek; Joseph, Joy; Kalyanaraman, Balaraman] Med Coll Wisconsin, Free Rad Res Ctr, Milwaukee, WI 53226 USA.
[Herman, Eugene] US FDA, Div Drug Safety Res, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
RP Rao, VA (reprint author), US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA.
EM ashutosh.rao@fda.hhs.gov
RI Zielonka, Jacek/N-9546-2014; Parekh, Palak/B-7042-2015
OI Zielonka, Jacek/0000-0002-2524-0145; Parekh, Palak/0000-0001-9201-5194
FU Food and Drug Administration (FDA) Critical Path Initiative; National
Cancer Institute-FDA Interagency Oncology Task Force Fellowship Program;
National Cancer Institute [HHSN261200800001E, R01 CA152810]
FX The authors would like to acknowledge support from the Food and Drug
Administration (FDA) Critical Path Initiative and the National Cancer
Institute-FDA Interagency Oncology Task Force Fellowship Program. The
electron microscopy work was funded in part from the National Cancer
Institute, Contract # HHSN261200800001E. The Mito-Tempol (4) synthesis
was supported by a grant from the National Cancer Institute, R01
CA152810. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 57
TC 21
Z9 22
U1 0
U2 12
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 5
PY 2013
VL 8
IS 8
AR e70575
DI 10.1371/journal.pone.0070575
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 218XC
UT WOS:000324465000090
PM 23940596
ER
PT J
AU Ho, J
Ondos, J
Ning, H
Smith, S
Kreisl, T
Iwamoto, F
Sul, J
Kim, L
McNeil, K
Krauze, A
Shankavaram, U
Fine, HA
Camphausen, K
AF Ho, Jennifer
Ondos, John
Ning, Holly
Smith, Sharon
Kreisl, Teri
Iwamoto, Fabio
Sul, Joohee
Kim, Lyndon
McNeil, Kate
Krauze, Andra
Shankavaram, Uma
Fine, Howard A.
Camphausen, Kevin
TI Chemoirradiation for Glioblastoma Multiforme: The National Cancer
Institute Experience
SO PLOS ONE
LA English
DT Article
ID NEWLY-DIAGNOSED GLIOBLASTOMA; RECURSIVE PARTITIONING ANALYSIS;
HIGH-GRADE GLIOMAS; RADIATION-THERAPY; PROGNOSTIC-SIGNIFICANCE; ADJUVANT
TEMOZOLOMIDE; VOLUMETRIC-ANALYSIS; MALIGNANT GLIOMAS; PHASE-II; SURVIVAL
AB Purpose: Standard treatment for glioblastoma (GBM) is surgery followed by radiation (RT) and temozolomide (TMZ). While there is variability in survival based on several established prognostic factors, the prognostic utility of other factors such as tumor size and location are not well established.
Experimental Design: The charts of ninety two patients with GBM treated with RT at the National Cancer Institute (NCI) between 1998 and 2012 were retrospectively reviewed. Most patients received RT with concurrent and adjuvant TMZ. Topographic locations were classified using preoperative imaging. Gross tumor volumes were contoured using treatment planning systems utilizing both pre-operative and post-operative MR imaging.
Results: At a median follow-up of 18.7 months, the median overall survival (OS) and progression-free survival (PFS) for all patients was 17.9 and 7.6 months. Patients with the smallest tumors had a median OS of 52.3 months compared to 16.3 months among patients with the largest tumors, P = 0.006. The patients who received bevacizumab after recurrence had a median OS of 23.3 months, compared to 16.3 months in patients who did not receive it, P = 0.0284. The median PFS and OS in patients with periventricular tumors was 5.7 and 17.5 months, versus 8.9 and 23.3 months in patients with non-periventricular tumors, P = 0.005.
Conclusions: Survival in our cohort was comparable to the outcome of the defining EORTC-NCIC trial establishing the use of RT+TMZ. This study also identifies several potential prognostic factors that may be useful in stratifying patients.
C1 [Ho, Jennifer; Smith, Sharon; Krauze, Andra; Shankavaram, Uma; Camphausen, Kevin] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Kreisl, Teri; Iwamoto, Fabio; Sul, Joohee; McNeil, Kate; Fine, Howard A.] NCI, Neurooncol Branch, NIH, Bethesda, MD 20892 USA.
[Ondos, John; Ning, Holly] Radiat Management Associates, Bethesda, MD USA.
[Kim, Lyndon] Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA.
RP Camphausen, K (reprint author), NCI, Radiat Oncol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM camphauk@mail.nih.gov
FU National Cancer Institute, NIH
FX This work was supported by the intramural research program of the
National Cancer Institute, NIH. The funders had no role in the study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 36
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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 AUG 5
PY 2013
VL 8
IS 8
AR e70745
DI 10.1371/journal.pone.0070745
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 218XC
UT WOS:000324465000128
PM 23940635
ER
PT J
AU Jacob, ST
Pavlinac, PB
Nakiyingi, L
Banura, P
Baeten, JM
Morgan, K
Magaret, A
Manabe, Y
Reynolds, SJ
Liles, WC
Wald, A
Joloba, ML
Mayanja-Kizza, H
Scheld, WM
AF Jacob, Shevin T.
Pavlinac, Patricia B.
Nakiyingi, Lydia
Banura, Patrick
Baeten, Jared M.
Morgan, Karen
Magaret, Amalia
Manabe, Yuka
Reynolds, Steven J.
Liles, W. Conrad
Wald, Anna
Joloba, Moses L.
Mayanja-Kizza, Harriet
Scheld, W. Michael
TI Mycobacterium tuberculosis Bacteremia in a Cohort of HIV-Infected
Patients Hospitalized with Severe Sepsis in Uganda-High Frequency, Low
Clinical Sand Derivation of a Clinical Prediction Score
SO PLOS ONE
LA English
DT Article
ID SUB-SAHARAN AFRICA; DIAGNOSTIC-ACCURACY; SEPTIC SHOCK; ADULTS;
IMMUNODEFICIENCY; CONFIRMATION; PREVALENCE; MANAGEMENT; TANZANIA; AREAS
AB Background: When manifested as Mycobacterium tuberculosis (MTB) bacteremia, disseminated MTB infection clinically mimics other serious blood stream infections often hindering early diagnosis and initiation of potentially life-saving anti-tuberculosis therapy. In a cohort of hospitalized HIV-infected Ugandan patients with severe sepsis, we report the frequency, management and outcomes of patients with MTB bacteremia and propose a risk score based on clinical predictors of MTB bacteremia.
Methods: We prospectively enrolled adult patients with severe sepsis at two Ugandan hospitals and obtained blood cultures for MTB identification. Multivariable logistic regression modeling was used to determine predictors of MTB bacteremia and to inform the stratification of patients into MTB bacteremia risk categories based on relevant patient characteristics.
Results: Among 368 HIV-infected patients with a syndrome of severe sepsis, eighty-six (23%) had MTB bacteremia. Patients with MTB bacteremia had a significantly lower median CD4 count (17 vs 64 lymphocytes/mm(3), p<0.001) and a higher 30-day mortality (53% vs 32%, p = 0.001) than patients without MTB bacteremia. A minority of patients with MTB bacteremia underwent standard MTB diagnostic testing (24%) or received empiric anti-tuberculosis therapy (15%). Independent factors associated with MTB bacteremia included male sex, increased heart rate, low CD4 count, absence of highly active anti-retroviral therapy, chief complaint of fever, low serum sodium and low hemoglobin. A risk score derived from a model containing these independent predictors had good predictive accuracy [area under the curve = 0.85, 95% CI 0.80-0.89].
Conclusions: Nearly 1 in 4 adult HIV-infected patients hospitalized with severe sepsis in 2 Ugandan hospitals had MTB bacteremia. Among patients in whom MTB was suspected, standard tests for diagnosing pulmonary MTB were inaccurate for correctly classifying patients with or without bloodstream MTB infection. A MTB bacteremia risk score can improve early diagnosis of MTB bacteremia particularly in settings with increased HIV and MTB co-infection.
C1 [Jacob, Shevin T.; Baeten, Jared M.; Liles, W. Conrad; Wald, Anna] Univ Washington, Dept Med, Seattle, WA 98195 USA.
[Jacob, Shevin T.] Univ Washington, Int Resp & Severe Illness Ctr INTERSECT, Seattle, WA 98195 USA.
[Pavlinac, Patricia B.; Baeten, Jared M.; Wald, Anna] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Nakiyingi, Lydia; Mayanja-Kizza, Harriet] Makerere Univ, Coll Hlth Sci, Sch Med, Kampala, Uganda.
[Nakiyingi, Lydia] Makerere Univ, Infect Dis Inst, Kampala, Uganda.
[Banura, Patrick] Masaka Reg Referral Hosp, Masaka, Uganda.
[Baeten, Jared M.] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA.
[Morgan, Karen] Joint Clin Res Ctr, JCRC TB Lab, Mengo, Uganda.
[Magaret, Amalia; Wald, Anna] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA.
[Magaret, Amalia] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA.
[Manabe, Yuka; Reynolds, Steven J.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Reynolds, Steven J.; Wald, Anna] Rakai Hlth Sci Program, Kalisizo, Uganda.
[Reynolds, Steven J.] NIH, Dept Intramural Res, Bethesda, MD 20892 USA.
[Joloba, Moses L.] Makerere Univ, Dept Med Microbiol, Kampala, Uganda.
[Scheld, W. Michael] Univ Virginia, Dept Med, Charlottesville, VA USA.
RP Jacob, ST (reprint author), Univ Washington, Dept Med, Seattle, WA 98195 USA.
EM sjacob2@uw.edu
FU Pfizer, Inc.; Rakai Health Sciences Program through the Division of
Intramural Research, National Institute of Allergy and Infectious
Diseases, National Institutes of Health; National Institutes of Health
[K24 (AI 071113)]; University of Washington STD/AIDS Research Training
Program from the National Institutes of Health [T32 (AI007140)]
FX Primary funding for the study was from an Investigator-Initiated Award
provided by Pfizer, Inc. Pfizer, Inc. had no role in the design and
conduct of the study; the collection, management, analysis, and
interpretation of the data; or the preparation, review or approval of
the manuscript. Additional non-grant support was provided by the Rakai
Health Sciences Program through the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health. In addition, AW is supported by a National
Institutes of Health K24 (AI 071113) and PP is supported by the
University of Washington STD/AIDS Research Training Program, T32
(AI007140) from 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 29
TC 21
Z9 21
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 AUG 5
PY 2013
VL 8
IS 8
AR e70305
DI 10.1371/journal.pone.0070305
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 218XC
UT WOS:000324465000051
PM 23940557
ER
PT J
AU Lam, TK
Moore, SC
Brinton, LA
Smith, L
Hollenbeck, AR
Gierach, GL
Freedman, ND
AF Lam, Tram Kim
Moore, Steve C.
Brinton, Louise A.
Smith, Llewellyn
Hollenbeck, Albert R.
Gierach, Gretchen L.
Freedman, Neal D.
TI Anthropometric Measures and Physical Activity and the Risk of Lung
Cancer in Never-Smokers: A Prospective Cohort Study
SO PLOS ONE
LA English
DT Article
ID BODY-MASS INDEX; WAIST CIRCUMFERENCE; WOMENS HEALTH; OLDER WOMEN;
ASSOCIATION; MORTALITY; DISEASE; FAT; METAANALYSIS; RELIABILITY
AB Worldwide, lung cancer in never-smokers is ranked the seventh most common cause of cancer death; however, the etiology of lung cancer in never-smokers is unclear. We investigated associations for body mass index (BMI) at various ages, waist circumference, hip circumference, and physical activity with lung cancer in 158,415 never-smokers of the NIH-AARP Diet and Health Study. Multivariable hazard ratios (HR) and 95% confidence intervals (CI) were estimated from Cox proportional hazards models. Over 11 years of follow-up, 532 lung cancer cases occurred. The risk estimate for obese (BMI >= 30 kg/m(2)) participants at baseline was 1.21 (95% CI = 0.95-1.53) relative to those with a normal BMI between 18.5 <= BMI<25.0. Overweight (25.0 <= BMI<30.0) at age 18 (HRoverweight-vs-normal = 1.51; 95% CI = 1.01-2.26) and time spent sitting (HR approximate to 3 hrs-vs<3 (hrs) = 1.32; 95% CI = 1.00-1.73) was each associated with lung cancer after adjustment for baseline BMI, as was waist (HRQ4vs-Q1 = 1.75; 95% CI = 1.09-2.79) and hip circumference (HRQ4-vs-Q1 = 0.62; 95% CI = 0.39-0.99), after mutual adjustment for each other and baseline BMI. No associations were observed for vigorous activity or television watching. In summary, using a large prospective cohort study, we found no evidence that BMI at baseline or middle age was associated with decreased lung cancer risk in never smokers. If anything, we observed some evidence for positive associations with a larger BMI or waist circumference.
C1 [Lam, Tram Kim] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Moore, Steve C.; Freedman, Neal D.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Brinton, Louise A.; Gierach, Gretchen L.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Smith, Llewellyn] Williams Coll, Williamstown, MA 01267 USA.
[Hollenbeck, Albert R.] AARP, Org & Tracking Res Dept, Washington, DC USA.
RP Lam, TK (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
EM lamt@mail.nih.gov
RI Brinton, Louise/G-7486-2015; Freedman, Neal/B-9741-2015; Moore,
Steven/D-8760-2016; Gierach, Gretchen/E-1817-2016
OI Brinton, Louise/0000-0003-3853-8562; Freedman, Neal/0000-0003-0074-1098;
Moore, Steven/0000-0002-8169-1661; Gierach, Gretchen/0000-0002-0165-5522
NR 32
TC 13
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U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 5
PY 2013
VL 8
IS 8
AR e70672
DI 10.1371/journal.pone.0070672
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 218XC
UT WOS:000324465000114
PM 23940620
ER
PT J
AU Madsen, DH
Jurgensen, HJ
Ingvarsen, S
Melander, MC
Albrechtsen, R
Hald, A
Holmbeck, K
Bugge, TH
Behrendt, N
Engelholm, LH
AF Madsen, Daniel H.
Jurgensen, Henrik J.
Ingvarsen, Signe
Melander, Maria C.
Albrechtsen, Reidar
Hald, Andreas
Holmbeck, Kenn
Bugge, Thomas H.
Behrendt, Niels
Engelholm, Lars H.
TI Differential Actions of the Endocytic Collagen Receptor uPARAP/Endo180
and the Collagenase MMP-2 in Bone Homeostasis
SO PLOS ONE
LA English
DT Article
ID PLASMINOGEN-ACTIVATOR RECEPTOR; MANNOSE RECEPTOR;
MATRIX-METALLOPROTEINASE-2 GENE; MATRIX METALLOPROTEINASES; MULTICENTRIC
OSTEOLYSIS; DENATURED COLLAGEN; IV COLLAGENASE; HUMAN BREAST;
TUMOR-CELLS; IN-VIVO
AB A well-coordinated remodeling of uncalcified collagen matrices is a pre-requisite for bone development and homeostasis. Collagen turnover proceeds through different pathways, either involving extracellular reactions exclusively, or being dependent on endocytic processes. Extracellular collagen degradation requires the action of secreted or membrane attached collagenolytic proteases, whereas the alternative collagen degradation pathway proceeds intracellularly after receptor-mediated uptake and delivery to the lysosomes. In this study we have examined the functional interplay between the extracellular collagenase, MMP-2, and the endocytic collagen receptor, uPARAP, by generating mice with combined deficiency of both components. In both uPARAP-deficient and MMP-2-deficient adult mice the length of the tibia and femur was decreased, along with a reduced bone mineral density and trabecular bone quality. An additional decrease in bone length was observed when combining the two deficiencies, pointing to both components being important for the remodeling processes in long bone growth. In agreement with results found by others, a different effect of MMP-2 deficiency was observed in the distinct bone structures of the calvaria. These membranous bones were found to be thickened in MMP-2-deficient mice, an effect likely to be related to an accompanying defect in the canalicular system. Surprisingly, both of the latter defects in MMP-2-deficient mice were counteracted by concurrent uPARAP deficiency, demonstrating that the collagen receptor does not support the same matrix remodeling processes as the MMP in the growth of the skull. We conclude that both uPARAP and MMP-2 take part in matrix turnover processes important for bone growth. However, in some physiological situations, these two components do not support the same step in the growth process.
C1 [Madsen, Daniel H.; Jurgensen, Henrik J.; Ingvarsen, Signe; Melander, Maria C.; Hald, Andreas; Behrendt, Niels; Engelholm, Lars H.] Univ Copenhagen, Rigshosp, Finsen Lab, Biotech Res & Innovat Ctr, DK-2100 Copenhagen, Denmark.
[Albrechtsen, Reidar] Univ Copenhagen, Dept Biomed Sci, Copenhagen, Denmark.
[Albrechtsen, Reidar] Univ Copenhagen, Biotech Res & Innovat Ctr, Copenhagen, Denmark.
[Holmbeck, Kenn] Natl Inst Dent & Craniofacial Res, Matrix Metalloproteinase Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA.
[Madsen, Daniel H.; Bugge, Thomas H.] Natl Inst Dent & Craniofacial Res, Proteases & Tissue Remodeling Sect, NIH, Bethesda, MD USA.
RP Madsen, DH (reprint author), Univ Copenhagen, Rigshosp, Finsen Lab, Biotech Res & Innovat Ctr, DK-2100 Copenhagen, Denmark.
EM daniel.madsen@nih.gov
OI Albrechtsen, Reidar/0000-0003-4180-1827; Madsen, Daniel
Hargboel/0000-0002-3183-6201; Engelholm, Lars/0000-0002-6616-1232
FU Danish Cancer Society; Danish Medical Research Council; Danish Cancer
Research Foundation; Novo Nordisk Foundation; Danish National Research
Foundation (Danish-Chinese Center for Proteases and Cancer); European
Community [201279]; Lundbeck Foundation; "Grosserer Alfred Nielsen og
Hustrus" foundation; NIDCR; Copenhagen University Hospital; University
of Copenhagen, Faculty of Science
FX This work was supported by the Danish Cancer Society, the Danish Medical
Research Council, the Danish Cancer Research Foundation, the Novo
Nordisk Foundation, the Danish National Research Foundation
(Danish-Chinese Center for Proteases and Cancer) and the European
Community's Seventh Framework Programme FP7/2007-2011 under grant
agreement no201279 (NB), by the Lundbeck Foundation (NB and LHE), the
"Grosserer Alfred Nielsen og Hustrus" foundation (LHE) and by the NIDCR
Intramural Research Program (THB and KH). The work was supported by
personal grants from Copenhagen University Hospital (DHM and HJJ), the
Lundbeck Foundation (DHM) and from the University of Copenhagen, Faculty
of Science (SI). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 51
TC 7
Z9 7
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 AUG 5
PY 2013
VL 8
IS 8
AR e71261
DI 10.1371/journal.pone.0071261
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 218XC
UT WOS:000324465000202
PM 23940733
ER
PT J
AU SanGiovanni, JP
Lee, PH
AF SanGiovanni, John Paul
Lee, Phil H.
TI AMD-Associated Genes Encoding Stress-Activated MAPK Pathway Constituents
Are Identified by Interval-Based Enrichment Analysis
SO PLOS ONE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; PROTEIN-KINASES;
THERAPEUTIC TARGETS; INDUCED RETINOPATHY; UNITED-STATES; JNK;
POLYMORPHISMS; PATHOGENESIS; INHIBITION
AB Purpose: To determine whether common DNA sequence variants within groups of genes encoding elements of stress-activated mitogen-activated protein kinase (MAPK) signaling pathways are, in aggregate, associated with advanced AMD (AAMD).
Methods: We used meta-regression and exact testing methods to identify AAMD-associated SNPs in 1177 people with AAMD and 1024 AMD-free elderly peers from 3 large-scale genotyping projects on the molecular genetics of AMD. SNPs spanning independent AAMD-associated genomic intervals were examined with a multi-locus-testing method (INRICH) for enrichment within five sets of genes encoding constituents of stress-activated MAPK signaling cascades.
Results: Four-of-five pathway gene sets showed enrichment with AAMD-associated SNPs; findings persisted after adjustment for multiple testing in two. Strongest enrichment signals (P = 0.006) existed in a c-Jun N-terminal kinase (JNK)/MAPK cascade (Science Signaling, STKE CMP_10827). In this pathway, seven independent AAMD-associated regions were resident in 6 of 25 genes examined. These included sequence variants in: 1) three MAP kinase kinase kinases (MAP3K4, MAP3K5, MAP3K9) that phosphorylate and activate the MAP kinase kinases MAP2K4 and MAP2K7 (molecules that phosphorylate threonine and tyrosine residues within the activation loop of JNK); 2) a target of MAP2K7 (JNK3A1) that activates complexes involved in transcriptional regulation of stress related genes influencing cell proliferation, apoptosis, motility, metabolism and DNA repair; and 3) NR2C2, a transcription factor activated by JNK1A1 (a drugable molecule influencing retinal cell viability in model systems). We also observed AAMD-related sequence variants resident in genes encoding PPP3CA (a drugable molecule that inactivates MAP3K5), and two genes (TGFB2, TGFBR2) encoding factors involved in MAPK sensing of growth factors/cytokines.
Conclusions: Linkage disequilibrium (LD)-independent genomic enrichment analysis yielded associations of AAMD with aggregates of functionally related genes encoding constituents of the JNK MAPK signaling pathway. FDA-approved drugs now exist to target constituents of stress-activated MAPK pathways and may offer reasonable approaches to preventing or treating AAMD.
C1 [SanGiovanni, John Paul] NEI, Clin Trials Branch, NIH, Bethesda, MD 20892 USA.
[Lee, Phil H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Analyt & Translat Genet Unit,Ctr Human Genet Res, Boston, MA USA.
RP SanGiovanni, JP (reprint author), NEI, Clin Trials Branch, NIH, Bethesda, MD 20892 USA.
EM jpsangio@post.harvard.edu
FU National Eye Institute
FX Funding for NEI-AMD was provided by the National Eye Institute. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 37
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Z9 6
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 5
PY 2013
VL 8
IS 8
AR e71239
DI 10.1371/journal.pone.0071239
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 218XC
UT WOS:000324465000199
PM 23940728
ER
PT J
AU Krug, K
Cicmil, N
Parker, AJ
Cumming, BG
AF Krug, Kristine
Cicmil, Nela
Parker, Andrew J.
Cumming, Bruce G.
TI A Causal Role for V5/MT Neurons Coding Motion-Disparity Conjunctions in
Resolving Perceptual Ambiguity
SO CURRENT BIOLOGY
LA English
DT Article
ID DECISION-RELATED ACTIVITY; VISUAL AREA V5/MT; BINOCULAR DISPARITY;
STEREOSCOPIC DEPTH; CORTICAL AREA; MT; MACAQUE; MICROSTIMULATION;
DIRECTION; CHOICE
AB Judgments about the perceptual appearance of visual objects require the combination of multiple parameters, like location, direction, color, speed, and depth. Our understanding of perceptual judgments has been greatly informed by studies of ambiguous figures, which take on different appearances depending upon the brain state of the observer. Here we probe the neural mechanisms hypothesized as responsible for judging the apparent direction of rotation of ambiguous structure from motion (SFM) stimuli. Resolving the rotation direction of SFM cylinders requires the conjoint decoding of direction of motion and binocular depth signals [1, 2]. Within cortical visual area V5/MT of two macaque monkeys, we applied electrical stimulation at sites with consistent multiunit tuning to combinations of binocular depth and direction of motion, while the monkey made perceptual decisions about the rotation of SFM stimuli. For both ambiguous and unambiguous SFM figures, rotation judgments shifted as if we had added a specific conjunction of disparity and motion signals to the stimulus elements. This is the first causal demonstration that the activity of neurons in V5/MT contributes directly to the perception of SFM stimuli and by implication to decoding the specific conjunction of disparity and motion, the two different visual cues whose combination drives the perceptual judgment.
C1 [Krug, Kristine; Cicmil, Nela; Parker, Andrew J.] Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 3PT, England.
[Cumming, Bruce G.] NEI, Lab Sensorimotor Res, NIH, Bethesda, MD 20892 USA.
RP Krug, K (reprint author), Univ Oxford, Dept Physiol Anat & Genet, Sherrington Bldg, Oxford OX1 3PT, England.
EM kristine.krug@dpag.ox.ac.uk
RI Parker, Andrew/I-7867-2013;
OI Parker, Andrew/0000-0001-5800-0407; Krug, Kristine/0000-0001-7119-9350
FU Wellcome Trust; US National Institutes of Health
FX K.K. is a Royal Society University Research Fellow; N.C. held an Usher
Cunningham Studentship (DPAG and Exeter College, Oxford). We would like
to thank Greg DeAngelis for allowing us to use his data and Rachel
Denison for help with the analysis. This work was supported by the
Wellcome Trust and the Intramural Research Program of the US National
Institutes of Health.
NR 31
TC 17
Z9 18
U1 0
U2 10
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0960-9822
J9 CURR BIOL
JI Curr. Biol.
PD AUG 5
PY 2013
VL 23
IS 15
BP 1454
EP 1459
DI 10.1016/j.cub.2013.06.023
PG 6
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 198NS
UT WOS:000322930200023
PM 23871244
ER
PT J
AU Lloyd-Smith, JO
AF Lloyd-Smith, James O.
TI Vacated niches, competitive release and the community ecology of
pathogen eradication
SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
LA English
DT Article
DE pathogen eradication; competitive release; ecological niche; monkeypox;
zoonosis; emerging infectious disease
ID INFECTIOUS-DISEASES; RINDERPEST ERADICATION; MONKEYPOX VIRUS;
TRANSMISSIBLE DISEASES; SMALLPOX VACCINATION; POLIO ERADICATION;
PUBLIC-HEALTH; EMERGENCE; CONGO; EPIDEMIOLOGY
AB A recurring theme in the epidemiological literature on disease eradication is that each pathogen occupies an ecological niche, and eradication of one pathogen leaves a vacant niche that favours the emergence of new pathogens to replace it. However, eminent figures have rejected this view unequivocally, stating that there is no basis to fear pathogen replacement and even that pathogen niches do not exist. After exploring the roots of this controversy, I propose resolutions to disputed issues by drawing on broader ecological theory, and advance a new consensus based on robust mechanistic principles. I argue that pathogen eradication (and cessation of vaccination) leads to a 'vacated niche', which could be re-invaded by the original pathogen if introduced. Consequences for other pathogens will vary, with the crucial mechanisms being competitive release, whereby the decline of one species allows its competitors to perform better, and evolutionary adaptation. Hence, eradication can cause a quantitative rise in the incidence of another infection, but whether this leads to emergence as an endemic pathogen depends on additional factors. I focus on the case study of human monkeypox and its rise following smallpox eradication, but also survey how these ideas apply to other pathogens and discuss implications for eradication policy.
C1 [Lloyd-Smith, James O.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA.
[Lloyd-Smith, James O.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Lloyd-Smith, JO (reprint author), Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, 610 Charles E Young Dr South, Los Angeles, CA 90095 USA.
EM jlloydsmith@ucla.edu
RI Lloyd-Smith, James/K-4080-2012
OI Lloyd-Smith, James/0000-0001-7941-502X
FU NSF [EF-0928690]; De Logi Chair in Biological Sciences; RAPIDD programme
of the Science & Technology Directorate, Department of Homeland
Security; Fogarty International Center, National Institutes of Health
FX I thank Petra Klepac, Anne Rimoin, Bryan Grenfell, Peter Hudson, and
members of my research group at UCLA for illuminating discussions. I am
grateful for the support of NSF grant no. EF-0928690, the De Logi Chair
in Biological Sciences, and the RAPIDD programme of the Science &
Technology Directorate, Department of Homeland Security and the Fogarty
International Center, National Institutes of Health.
NR 81
TC 17
Z9 17
U1 2
U2 36
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 0962-8436
J9 PHILOS T R SOC B
JI Philos. Trans. R. Soc. B-Biol. Sci.
PD AUG 5
PY 2013
VL 368
IS 1623
SI SI
AR UNSP 20120150
DI 10.1098/rstb.2012.0150
PG 12
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 173XC
UT WOS:000321114700013
PM 23798698
ER
PT J
AU Smith, DL
Cohen, JM
Chiyaka, C
Johnston, G
Gething, PW
Gosling, R
Buckee, CO
Laxminarayan, R
Hay, SI
Tatem, AJ
AF Smith, David L.
Cohen, Justin M.
Chiyaka, Christinah
Johnston, Geoffrey
Gething, Peter W.
Gosling, Roly
Buckee, Caroline O.
Laxminarayan, Ramanan
Hay, Simon I.
Tatem, Andrew J.
TI A sticky situation: the unexpected stability of malaria elimination
SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
LA English
DT Article
DE malaria elimination; malaria eradication; backwards bifurcation
ID SUB-SAHARAN AFRICA; PLASMODIUM-FALCIPARUM INFECTION; COMPETITIVE
DISPLACEMENT; WESTERN KENYA; UNITED-STATES; SOUTH-AFRICA; TRANSMISSION;
ERADICATION; BURDEN; ENDEMICITY
AB Malaria eradication involves eliminating malaria from every country where transmission occurs. Current theory suggests that the post-elimination challenges of remaining malaria-free by stopping transmission from imported malaria will have onerous operational and financial requirements. Although resurgent malaria has occurred in a majority of countries that tried but failed to eliminate malaria, a review of resurgence in countries that successfully eliminated finds only four such failures out of 50 successful programmes. Data documenting malaria importation and onwards transmission in these countries suggests malaria transmission potential has declined by more than 50-fold (i.e. more than 98%) since before elimination. These outcomes suggest that elimination is a surprisingly stable state. Elimination's 'stickiness' must be explained either by eliminating countries starting off qualitatively different from non-eliminating countries or becoming different once elimination was achieved. Countries that successfully eliminated were wealthier and had lower baseline endemicity than those that were unsuccessful, but our analysis shows that those same variables were at best incomplete predictors of the patterns of resurgence. Stability is reinforced by the loss of immunity to disease and by the health system's increasing capacity to control malaria transmission after elimination through routine treatment of cases with antimalarial drugs supplemented by malaria outbreak control. Human travel patterns reinforce these patterns; as malaria recedes, fewer people carry malaria from remote endemic areas to remote areas where transmission potential remains high. Establishment of an international resource with backup capacity to control large outbreaks can make elimination stickier, increase the incentives for countries to eliminate, and ensure steady progress towards global eradication. Although available evidence supports malaria elimination's stickiness at moderate-to-low transmission in areas with well-developed health systems, it is not yet clear if such patterns will hold in all areas. The sticky endpoint changes the projected costs of maintaining elimination and makes it substantially more attractive for countries acting alone, and it makes spatially progressive elimination a sensible strategy for a malaria eradication endgame.
C1 [Smith, David L.; Johnston, Geoffrey] Johns Hopkins Bloomberg, Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Smith, David L.; Johnston, Geoffrey] Johns Hopkins Bloomberg, Sch Publ Hlth, Malaria Res Inst, Baltimore, MD USA.
[Smith, David L.; Chiyaka, Christinah; Johnston, Geoffrey] Univ Florida, Emerging Pathogens Inst, Gainesville, FL USA.
[Smith, David L.; Laxminarayan, Ramanan] Ctr Dis Dynam Econ & Policy, Washington, DC USA.
[Smith, David L.; Hay, Simon I.; Tatem, Andrew J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Cohen, Justin M.] Clinton Hlth Access Initiat, Boston, MA USA.
[Gething, Peter W.; Hay, Simon I.] Univ Oxford, Dept Zool, Oxford, England.
[Gosling, Roly] Univ Calif San Francisco, Global Hlth Grp, Malaria Eliminat Initiat, San Francisco, CA 94143 USA.
[Buckee, Caroline O.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Ctr Communicable Dis Dynam, Boston, MA 02115 USA.
[Tatem, Andrew J.] Univ Southampton, Dept Geog & Environm, Southampton, Hants, England.
RP Smith, DL (reprint author), Johns Hopkins Bloomberg, Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
EM dlsmith@jhsph.edu
RI Smith, David/L-8850-2013; Hay, Simon/F-8967-2015;
OI Smith, David/0000-0003-4367-3849; Hay, Simon/0000-0002-0611-7272; Cohen,
Justin/0000-0003-4481-6784; Gething, Peter/0000-0001-6759-5449
FU Bloomberg Family Foundation; NIH/NIAID [U19AI089674]; Bill & Melinda
Gates Foundation [49446, 1032350, 1013170, 1068048]; RAPIDD program of
the Science and Technology Directorate, Department of Homeland Security;
Fogarty International Center, National Institutes of Health; Medical
Research Council, UK [K00669X]; Senior Research Fellowship from the
Wellcome Trust [095066]
FX Funding has come from the Bloomberg Family Foundation (D.L.S. and G.J.),
NIH/NIAID (U19AI089674: D.L.S., A.J.T. and G.J.), the Bill & Melinda
Gates Foundation (49446: D.L.S. and A.J.T.; 1032350: A.J.T.; 1013170:
J.M.C.; 1068048: P.W.G), and the RAPIDD program of the Science and
Technology Directorate, Department of Homeland Security and the Fogarty
International Center, National Institutes of Health (D.L.S., A.J.T. and
S.I.H.), The Medical Research Council, UK (K00669X: P.W.G.) and a Senior
Research Fellowship from the Wellcome Trust (095066: S.I.H.). The
Malaria Elimination Group provided intellectual support for this
research.
NR 121
TC 26
Z9 27
U1 4
U2 43
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 0962-8436
J9 PHILOS T R SOC B
JI Philos. Trans. R. Soc. B-Biol. Sci.
PD AUG 5
PY 2013
VL 368
IS 1623
SI SI
AR UNSP 20120145
DI 10.1098/rstb.2012.0145
PG 15
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 173XC
UT WOS:000321114700008
PM 23798693
ER
PT J
AU Ong, EC
Nesin, V
Long, CL
Bai, CX
Guz, JL
Ivanov, IP
Abramowitz, J
Birnbaumer, L
Humphrey, MB
Tsiokas, L
AF Ong, E-Ching
Nesin, Vasyl
Long, Courtney L.
Bai, Chang-Xi
Guz, Jan L.
Ivanov, Ivaylo P.
Abramowitz, Joel
Birnbaumer, Lutz
Humphrey, Mary Beth
Tsiokas, Leonidas
TI A TRPC1 Protein-dependent Pathway Regulates Osteoclast Formation and
Function
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID TRANSCRIPTION FACTOR NFATC1; OPERATED CA2+ ENTRY; MFA DOMAIN PROTEINS;
CRAC CHANNEL; PLASMA-MEMBRANE; TERMINAL DIFFERENTIATION;
CALCIUM-CHANNELS; STORE DEPLETION; ION SELECTIVITY; BETA-CATENIN
AB Ca2+ signaling is essential for bone homeostasis and skeletal development. Here, we show that the transient receptor potential canonical 1 (TRPC1) channel and the inhibitor of MyoD family, I-mfa, function antagonistically in the regulation of osteoclastogenesis. I-mfa null mice have an osteopenic phenotype characterized by increased osteoclast numbers and surface, which are normalized in mice lacking both Trpc1 and I-mfa. In vitro differentiation of pre-osteoclasts derived from I-mfa-deficient mice leads to an increased number of mature osteoclasts and higher bone resorption per osteoclast. These parameters return to normal levels in osteoclasts derived from double mutant mice. Consistently, whole cell currents activated in response to the depletion of intracellular Ca2+ stores are larger in pre-osteoclasts derived from I-mfa knock-out mice compared with currents in wild type mice and normalized in cells derived from double mutant mice, suggesting a cell-autonomous effect of I-mfa on TRPC1 in these cells. A new splice variant of TRPC1 (TRPC1 epsilon) was identified in early pre-osteoclasts. Heterologous expression of TRPC1 epsilon in HEK293 cells revealed that it is unique among all known TRPC1 isoforms in its ability to amplify the activity of the Ca2+ release-activated Ca2+ (CRAC) channel, mediating store-operated currents. TRPC1 epsilon physically interacts with Orai1, the pore-forming subunit of the CRAC channel, and I-mfa is recruited to the TRPC1 epsilon-Orai1 complex through TRPC1 epsilon suppressing CRAC channel activity. We propose that the positive and negative modulation of the CRAC channel by TRPC1 epsilon and I-mfa, respectively, fine-tunes the dynamic range of the CRAC channel regulating osteoclastogenesis.
C1 [Ong, E-Ching; Nesin, Vasyl; Bai, Chang-Xi; Guz, Jan L.; Tsiokas, Leonidas] Univ Oklahoma, Hlth Sci Ctr, Dept Cell Biol, Oklahoma City, OK 73014 USA.
[Long, Courtney L.; Humphrey, Mary Beth] Univ Oklahoma, Hlth Sci Ctr, Dept Med Rheumatol, Oklahoma City, OK 73014 USA.
[Ivanov, Ivaylo P.] Natl Univ Ireland Univ Coll Cork, BioSci Inst, Cork, Ireland.
[Ivanov, Ivaylo P.] Univ Utah, Dept Human Genet, Salt Lake City, UT 84112 USA.
[Abramowitz, Joel; Birnbaumer, Lutz] NIEHS, Neurobiol Lab, Div Intramural Res, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Humphrey, Mary Beth] Vet Affairs Med Ctr, Oklahoma City, OK 73014 USA.
RP Tsiokas, L (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Cell Biol, 975 NE 10th St, Oklahoma City, OK 73014 USA.
EM ltsiokas@ouhsc.edu
RI Abramowitz, Joel/A-2620-2015
FU National Institutes of Health Intramural Research Program from NIEHS
[Z01 ES101684]; NIDDK [DE019398NIDCR, R01DK59599]; Oklahoma Center for
Adult Stem Cells; [P20GM103639]; [P20GM104934NIGMS]
FX This work was supported, in whole or in part, by National Institutes of
Health Intramural Research Program Project Z01 ES101684 from NIEHS (to
L. B.), Grant DE019398NIDCR (to M. B. H.), Grant R01DK59599 from NIDDK,
and Grants P20GM103639 and P20GM104934NIGMS (to L. T.). This work was
also supported by the Oklahoma Center for Adult Stem Cells.
NR 58
TC 18
Z9 18
U1 0
U2 6
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 AUG 2
PY 2013
VL 288
IS 31
BP 22219
EP 22232
DI 10.1074/jbc.M113.459826
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 302HY
UT WOS:000330596300005
PM 23770672
ER
PT J
AU Cheung, KL
Lee, JH
Shu, L
Kim, JH
Sacks, DB
Kong, ANT
AF Cheung, Ka Lung
Lee, Jong Hun
Shu, Limin
Kim, Jung-Hwan
Sacks, David B.
Kong, Ah-Ng Tony
TI The Ras GTPase-activating-like Protein IQGAP1 Mediates Nrf2 Protein
Activation via the Mitogen-activated Protein Kinase/Extracellular
Signal-regulated Kinase (ERK) Kinase (MEK)-ERK Pathway
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID ANTIOXIDANT RESPONSE ELEMENT; BINDING PROTEIN; NUCLEAR TRANSLOCATION;
OXIDATIVE STRESS; HEME OXYGENASE-1; GENE-EXPRESSION; HEPG2 CELLS;
CALMODULIN; INDUCTION; IDENTIFICATION
AB Nrf2 plays a critical role in the regulation of cellular oxidative stress. MEK-ERK activation has been shown to be one of the major pathways resulting in the activation of Nrf2 and induction of Nrf2 downstream targets, including phase II detoxifying/antioxidant genes in response to oxidative stress and xenobiotics. In this study, IQGAP1 (IQ motif-containing GTPase-activating protein 1), a new Nrf2 interaction partner that we have published previously, was found to modulate MEK-ERK-mediated Nrf2 activation and induction of phase II detoxifying/antioxidant genes. Nrf2 binds directly to the IQ domain (amino acids 699-905) of IQGAP1. Knockdown of IQGAP1 significantly attenuated phenethyl isothiocyanate-or MEK-mediated activation of the MEK-ERK-Nrf2 pathway. Knockdown of IQGAP1 also attenuated MEK-mediated increased stability of Nrf2, which in turn was associated with a decrease in the nuclear translocation of Nrf2 and a decrease in the expression of phase II detoxifying/antioxidant genes. In the aggregate, these results suggest that IQGAP1 may play an important role in the MEK-ERK-Nrf2 signaling pathway.
C1 [Cheung, Ka Lung] Rutgers State Univ, Ernest Mario Sch Pharm, Grad Program Pharmaceut Sci, Piscataway, NJ 08854 USA.
[Cheung, Ka Lung; Lee, Jong Hun; Shu, Limin; Kim, Jung-Hwan; Kong, Ah-Ng Tony] Rutgers State Univ, Ernest Mario Sch Pharm, Dept Pharmaceut, Piscataway, NJ 08854 USA.
[Sacks, David B.] NIH, Dept Lab Med, Bethesda, MD 20892 USA.
RP Kong, ANT (reprint author), Rutgers State Univ, Ernest Mario Sch Pharm, Dept Pharmaceut, 160 Frelinghuysen Rd, Piscataway, NJ 08854 USA.
EM kongt@pharmacy.rutgers.edu
OI Lee, Jong Hun/0000-0002-3083-7595; Sacks, David/0000-0003-3100-0735
NR 35
TC 15
Z9 15
U1 1
U2 6
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 AUG 2
PY 2013
VL 288
IS 31
BP 22378
EP 22386
DI 10.1074/jbc.M112.444182
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 302HY
UT WOS:000330596300019
PM 23788642
ER
PT J
AU Huang, ZJ
Tatem, AJ
AF Huang, Zhuojie
Tatem, Andrew J.
TI Global malaria connectivity through air travel
SO MALARIA JOURNAL
LA English
DT Article
ID PLASMODIUM-FALCIPARUM; ARTEMISININ RESISTANCE; IMPORTED MALARIA;
PARASITE CLEARANCE; AIRPORT MALARIA; RISK; ELIMINATION; CENTRALITY;
MOVEMENT; AFRICA
AB Background: Air travel has expanded at an unprecedented rate and continues to do so. Its effects have been seen on malaria in rates of imported cases, local outbreaks in non-endemic areas and the global spread of drug resistance. With elimination and global eradication back on the agenda, changing levels and compositions of imported malaria in malaria-free countries, and the threat of artemisinin resistance spreading from Southeast Asia, there is a need to better understand how the modern flow of air passengers connects each Plasmodium falciparum-and Plasmodium vivax-endemic region to the rest of the world.
Methods: Recently constructed global P. falciparum and P. vivax malaria risk maps, along with data on flight schedules and modelled passenger flows across the air network, were combined to describe and quantify global malaria connectivity through air travel. Network analysis approaches were then utilized to describe and quantify the patterns that exist in passenger flows weighted by malaria prevalence. Finally, the connectivity within and to the Southeast Asia region where the threat of imported artemisinin resistance arising is highest, was examined to highlight risk routes for its spread.
Results: The analyses demonstrate the substantial connectivity that now exists between and from malaria-endemic regions through air travel. While the air network provides connections to previously isolated malarious regions, it is clear that great variations exist, with significant regional communities of airports connected by higher rates of flow standing out. The structures of these communities are often not geographically coherent, with historical, economic and cultural ties evident, and variations between P. falciparum and P. vivax clear. Moreover, results highlight how well connected the malaria-endemic areas of Africa are now to Southeast Asia, illustrating the many possible routes that artemisinin-resistant strains could take.
Discussion: The continuing growth in air travel is playing an important role in the global epidemiology of malaria, with the endemic world becoming increasingly connected to both malaria-free areas and other endemic regions. The research presented here provides an initial effort to quantify and analyse the connectivity that exists across the malaria-endemic world through air travel, and provide a basic assessment of the risks it results in for movement of infections.
C1 [Huang, Zhuojie] Penn State Univ, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
[Huang, Zhuojie] Penn State Univ, Dept Biol, University Pk, PA 16802 USA.
[Huang, Zhuojie] Univ Florida, Dept Geog, Gainesville, FL 32611 USA.
[Huang, Zhuojie] Univ Florida, Emerging Pathogens Inst, Gainesville, FL USA.
[Tatem, Andrew J.] Univ Southampton, Dept Geog & Environm, Southampton, Hants, England.
[Tatem, Andrew J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Huang, ZJ (reprint author), Penn State Univ, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
EM seenhzj@gmail.com
FU Bill and Melinda Gates Foundation [49446, 1032350]; NIH/NIAID
[U19AI089674]; RAPIDD program of the Science & Technology Directorate,
Department of Homeland Security; Fogarty International Center, National
Institutes of Health, USA
FX We thank Dr Peter Gething and Professor Simon Hay for sharing the
malaria datasets. AJT is supported by grants from the Bill and Melinda
Gates Foundation (#49446, #1032350) and NIH/NIAID (#U19AI089674). AJT
also acknowledges funding support from the RAPIDD program of the Science
& Technology Directorate, Department of Homeland Security, and the
Fogarty International Center, National Institutes of Health, USA. This
work forms part of the output of the Vector-borne disease airport
importation risk project (www.vbd-air.com) and the human mobility
mapping project (www.thummp.org).
NR 61
TC 13
Z9 16
U1 2
U2 22
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1475-2875
J9 MALARIA J
JI Malar. J.
PD AUG 2
PY 2013
VL 12
AR UNSP 269
DI 10.1186/1475-2875-12-269
PG 11
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA 214YZ
UT WOS:000324177100001
PM 23914776
ER
PT J
AU Winter, DK
Endoma-Arias, MA
Hudlicky, T
Beutler, JA
Porco, JA
AF Winter, Dana K.
Endoma-Arias, Mary Ann
Hudlicky, Tomas
Beutler, John A.
Porco, John A., Jr.
TI Enantioselective Total Synthesis and Biological Evaluation of
(+)-Kibdelone A and a Tetrahydroxanthone Analogue
SO JOURNAL OF ORGANIC CHEMISTRY
LA English
DT Article
ID NATURALLY-OCCURRING XANTHONES; FLUORINATED ALCOHOLS; PSEUDOMONAS-PUTIDA;
NATURAL-PRODUCTS; PHOTOCYCLIZATION; HYDROARYLATION; COMPLEXES; TOLUENE;
HETEROARENES; DERIVATIVES
AB The total synthesis of kibdelone A has been accomplished via In(III)-catalyzed arylation of a heterocyclic quinone monoketal and iodine-mediated oxidative photochemical electrocyclization for construction of the ABCD ring moiety. Enzymatic dihydroxylation of methyl 2-halobenzoate substrates was employed for synthesis of activated 2-halo-cyclohexene F-ring fragments. A one pot oxa-Michael/Friedel-Crafts process allowed access to the first simplified DEF ring analogues of the kibdelones.
C1 [Winter, Dana K.; Porco, John A., Jr.] Boston Univ, Dept Chem, Ctr Chem Methodol & Lib Dev CMLD BU, Boston, MA 02215 USA.
[Endoma-Arias, Mary Ann; Hudlicky, Tomas] Brock Univ, Dept Chem, St Catharines, ON L2S 3A1, Canada.
[Endoma-Arias, Mary Ann; Hudlicky, Tomas] Brock Univ, Ctr Biotechnol, St Catharines, ON L2S 3A1, Canada.
[Beutler, John A.] NCI, Mol Targets Lab, Frederick, MD 21702 USA.
RP Porco, JA (reprint author), Boston Univ, Dept Chem, Ctr Chem Methodol & Lib Dev CMLD BU, 590 Commonwealth Ave, Boston, MA 02215 USA.
EM porco@bu.edu
FU National Institutes of Health [RO1 CA137270]; Natural Sciences and
Engineering Research Council of Canada (NSERC); Canada Research Chair
Program; Canada Foundation for Innovation (CFI); TDC Research, Inc.; TDC
Research Foundation; Brock University; Intramural Research Program of
the NIH; National Cancer Institute Center for Cancer Research; FQRNT
(Fonds de Recherche Nature et Technologies du Quebec)
FX Financial support from the National Institutes of Health (RO1 CA137270),
the Natural Sciences and Engineering Research Council of Canada (NSERC)
(Idea to Innovation and Discovery Grants), the Canada Research Chair
Program, the Canada Foundation for Innovation (CFI), TDC Research, Inc.,
TDC Research Foundation, Brock University, the Intramural Research
Program of the NIH, National Cancer Institute Center for Cancer
Research, and FQRNT (Fonds de Recherche Nature et Technologies du
Quebec) is gratefully acknowledged. We thank Drs. David L. Sloman
(Merck) and Pieter Bos (Boston University) for helpful discussions and
Prof. Rob Capon (University of Queensland) and Dr. Ernest Lacy
(Microbial Screening Technologies) for providing spectra and samples of
kibdelone A.
NR 39
TC 16
Z9 16
U1 4
U2 43
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-3263
J9 J ORG CHEM
JI J. Org. Chem.
PD AUG 2
PY 2013
VL 78
IS 15
BP 7617
EP 7626
DI 10.1021/jo401169z
PG 10
WC Chemistry, Organic
SC Chemistry
GA 197LQ
UT WOS:000322853100025
PM 23834060
ER
PT J
AU Metwalli, AR
Pinto, PA
AF Metwalli, Adam R.
Pinto, Peter A.
TI Commentary on: "Focal cryosurgical ablation of the prostate: A single
institute's perspective"
SO BMC UROLOGY
LA English
DT Editorial Material
DE Prostate cancer; Therapy; Focal; Cryoablation; Image guided surgery
ID CANCER
AB The morbidity of whole gland treatment for prostate cancer is significant. Given the low risk of prostate cancer specific mortality for most men diagnosed with prostate cancer, alternative therapies such as sub-total or hemi-ablation of the prostate and focal ablation of prostate tumors are being investigated. The developing role of imaging for prostate tumors will dramatically change and likely improve the treatment morbidity for low risk prostate tumors. Commentary on: http://www.biomedcentral.com/1471-2490/13/2.
C1 [Metwalli, Adam R.; Pinto, Peter A.] NCI, Urol Oncol Branch, NIH, Bethesda, MD USA.
RP Metwalli, AR (reprint author), NCI, Urol Oncol Branch, NIH, Bldg 10,Room 2W-5940,10 Ctr Dr,MSC 1210,2089s, Bethesda, MD USA.
EM adam.metwalli@nih.gov
NR 9
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 1471-2490
J9 BMC UROL
JI BMC Urol.
PD AUG 2
PY 2013
VL 13
AR 39
DI 10.1186/1471-2490-13-39
PG 2
WC Urology & Nephrology
SC Urology & Nephrology
GA 200FK
UT WOS:000323053000001
PM 23915359
ER
PT J
AU Francalacci, P
Morelli, L
Angius, A
Berutti, R
Reinier, F
Atzeni, R
Pilu, R
Busonero, F
Maschio, A
Zara, I
Sanna, D
Useli, A
Urru, MF
Marcelli, M
Cusano, R
Oppo, M
Zoledziewska, M
Pitzalis, M
Deidda, F
Porcu, E
Poddie, F
Kang, HM
Lyons, R
Tarrier, B
Gresham, JB
Li, BS
Tofanelli, S
Alonso, S
Dei, M
Lai, S
Mulas, A
Whalen, MB
Uzzau, S
Jones, C
Schlessinger, D
Abecasis, GR
Sanna, S
Sidore, C
Cucca, F
AF Francalacci, Paolo
Morelli, Laura
Angius, Andrea
Berutti, Riccardo
Reinier, Frederic
Atzeni, Rossano
Pilu, Rosella
Busonero, Fabio
Maschio, Andrea
Zara, Ilenia
Sanna, Daria
Useli, Antonella
Urru, Maria Francesca
Marcelli, Marco
Cusano, Roberto
Oppo, Manuela
Zoledziewska, Magdalena
Pitzalis, Maristella
Deidda, Francesca
Porcu, Eleonora
Poddie, Fausto
Kang, Hyun Min
Lyons, Robert
Tarrier, Brendan
Gresham, Jennifer Bragg
Li, Bingshan
Tofanelli, Sergio
Alonso, Santos
Dei, Mariano
Lai, Sandra
Mulas, Antonella
Whalen, Michael B.
Uzzau, Sergio
Jones, Chris
Schlessinger, David
Abecasis, Gonalo R.
Sanna, Serena
Sidore, Carlo
Cucca, Francesco
TI Low-Pass DNA Sequencing of 1200 Sardinians Reconstructs European
Y-Chromosome Phylogeny
SO SCIENCE
LA English
DT Article
ID HUMAN-EVOLUTION; MODERN HUMANS; AFRICA; ORIGIN; LEGACY; TREE; ROOT
AB Genetic variation within the male-specific portion of the Y chromosome (MSY) can clarify the origins of contemporary populations, but previous studies were hampered by partial genetic information. Population sequencing of 1204 Sardinian males identified 11,763 MSY single-nucleotide polymorphisms, 6751 of which have not previously been observed. We constructed a MSY phylogenetic tree containing all main haplogroups found in Europe, along with many Sardinian-specific lineage clusters within each haplogroup. The tree was calibrated with archaeological data from the initial expansion of the Sardinian population similar to 7700 years ago. The ages of nodes highlight different genetic strata in Sardinia and reveal the presumptive timing of coalescence with other human populations. We calculate a putative age for coalescence of similar to 180,000 to 200,000 years ago, which is consistent with previous mitochondrial DNA-based estimates.
C1 [Francalacci, Paolo; Morelli, Laura; Sanna, Daria; Useli, Antonella] Univ Sassari, Dipartimento Sci Nat & Terr, I-07100 Sassari, Italy.
[Angius, Andrea; Pilu, Rosella; Busonero, Fabio; Maschio, Andrea; Zoledziewska, Magdalena; Pitzalis, Maristella; Deidda, Francesca; Porcu, Eleonora; Dei, Mariano; Lai, Sandra; Mulas, Antonella; Whalen, Michael B.; Sanna, Serena; Sidore, Carlo; Cucca, Francesco] CNR, IRGB, Monserrato, Italy.
[Angius, Andrea; Berutti, Riccardo; Reinier, Frederic; Atzeni, Rossano; Zara, Ilenia; Urru, Maria Francesca; Marcelli, Marco; Cusano, Roberto; Oppo, Manuela; Jones, Chris] Ctr Adv Studies Res & Dev Sardinia CRS4, Pula, Italy.
[Berutti, Riccardo; Zoledziewska, Magdalena; Pitzalis, Maristella; Deidda, Francesca; Porcu, Eleonora; Poddie, Fausto; Uzzau, Sergio; Sidore, Carlo; Cucca, Francesco] Univ Sassari, Dipartimento Sci Biomed, I-07100 Sassari, Italy.
[Busonero, Fabio; Maschio, Andrea; Porcu, Eleonora; Kang, Hyun Min; Abecasis, Gonalo R.; Sidore, Carlo] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Lyons, Robert; Tarrier, Brendan; Gresham, Jennifer Bragg] Univ Michigan, DNA Sequencing Core, Ann Arbor, MI 48109 USA.
[Li, Bingshan] Vanderbilt Univ, Dept Mol Physiol & Biophys, Ctr Human Genet Res, Nashville, TN 37235 USA.
[Tofanelli, Sergio] Univ Pisa, Dipartimento Biol, I-56126 Pisa, Italy.
[Alonso, Santos] Univ Pais Vasco Euskal Herriko Unibertsitatea, Dept Genet Antropol Fis & Fisiol Anim, Bilbao 48080, Spain.
[Uzzau, Sergio] Porto Conte Ric, I-07041 Sassari, Italy.
[Schlessinger, David] NIA, Genet Lab, Baltimore, MD 21224 USA.
RP Francalacci, P (reprint author), Univ Sassari, Dipartimento Sci Nat & Terr, I-07100 Sassari, Italy.
EM pfrancalacci@uniss.it; fcucca@uniss.it
RI Angius, Andrea/P-9549-2015; Alonso, Santos/L-8316-2014;
OI sanna, serena/0000-0002-3768-1749; Angius, Andrea/0000-0003-2596-6461;
Angius, Andrea/0000-0001-9372-1162; Alonso, Santos/0000-0003-0221-4048;
Mulas, Antonella/0000-0002-6856-1483; Pitzalis,
Maristella/0000-0003-4975-6987; WHALEN,
MICHAELBERNARD/0000-0001-7300-8511; Sidore, Carlo/0000-0001-7504-7477;
FRANCALACCI, Paolo/0000-0001-7912-162X
FU NIH from the National Institute of Aging [NO1-AG-1-2109]; Sardinian
Autonomous Region [7/2009, cRP3-154, cRP2-597]; Fondazione Banco di
Sardegna; Basque Government [G. I. C. IT-542-10]; National Human Genome
Research Institute [HG005581, HG005552, HG006513, HG007022]
FX This research was supported in part by NIH contract NO1-AG-1-2109 from
the National Institute of Aging to the IRGB institute; by Sardinian
Autonomous Region (L. R. no. 7/2009) grants cRP3-154 to F. C. and
cRP2-597 to P. F.; by Fondazione Banco di Sardegna grants to P. F. and
L. M.; by Basque Government grant G. I. C. IT-542-10 to S. A.; and by
National Human Genome Research Institute grants HG005581, HG005552,
HG006513, and HG007022 to G. R. A. We are grateful to all the Sardinian
donors for providing blood samples. We also thank the 1000 Genomes
Project consortium for making available their sequencing data, in
compliance with the Fort Lauderdale principles. We thank H. Skaletsky
for detailed information about sequence blocks on the Y chromosome; M.
Uda and R. Nagaraja for useful comments; C. Calo, D. Luiselli, and C. de
la Rua for providing some non-Sardinian samples; E. Garau, M. Rendeli,
A. Moravetti, and B. Wilkens for the archaeological background; and the
CRS4 HPC group for their IT support, in particular L. Leoni and C.
Podda. Genotype data have been deposited at the European Genome-phenome
Archive (EGA, www.ebi.ac.uk/ega/), which is hosted by the European
Bioinformatics Institute, under accession number EGAS00001000532.
NR 18
TC 44
Z9 46
U1 2
U2 45
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD AUG 2
PY 2013
VL 341
IS 6145
BP 565
EP 569
DI 10.1126/science.1237947
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 193UJ
UT WOS:000322586700058
PM 23908240
ER
PT J
AU Hersh, WR
Weiner, MG
Embi, PJ
Logan, JR
Payne, PRO
Bernstam, EV
Lehmann, HP
Hripcsak, G
Hartzog, TH
Cimino, JJ
Saltz, JH
AF Hersh, William R.
Weiner, Mark G.
Embi, Peter J.
Logan, Judith R.
Payne, Philip R. O.
Bernstam, Elmer V.
Lehmann, Harold P.
Hripcsak, George
Hartzog, Timothy H.
Cimino, James J.
Saltz, Joel H.
TI Caveats for the Use of Operational Electronic Health Record Data in
Comparative Effectiveness Research
SO MEDICAL CARE
LA English
DT Article
DE comparative effectiveness research; electronic health records; clinical
data; coded (claims) data; biomedical informatics
ID TYPE-2 DIABETES-MELLITUS; MEDICAL-RECORDS; PRIMARY-CARE; ADMINISTRATIVE
DATA; OUTCOMES RESEARCH; CLINICAL-DATA; SECONDARY USE; CLAIMS DATA;
QUALITY; IDENTIFICATION
AB The growing amount of data in operational electronic health record systems provides unprecedented opportunity for its reuse for many tasks, including comparative effectiveness research. However, there are many caveats to the use of such data. Electronic health record data from clinical settings may be inaccurate, incomplete, transformed in ways that undermine their meaning, unrecoverable for research, of unknown provenance, of insufficient granularity, and incompatible with research protocols. However, the quantity and real-world nature of these data provide impetus for their use, and we develop a list of caveats to inform would-be users of such data as well as provide an informatics roadmap that aims to insure this opportunity to augment comparative effectiveness research can be best leveraged.
C1 [Hersh, William R.; Logan, Judith R.] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97239 USA.
[Weiner, Mark G.] AstraZeneca, Wilmington, DE USA.
[Embi, Peter J.; Payne, Philip R. O.] Ohio State Univ, Wexner Med Ctr, Columbus, OH 43210 USA.
[Bernstam, Elmer V.] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA.
[Lehmann, Harold P.] Johns Hopkins Univ, Div Hlth Sci Informat, Baltimore, MD USA.
[Hripcsak, George] Columbia Univ, Dept Biomed Informat, New York, NY USA.
[Hartzog, Timothy H.] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA.
[Cimino, James J.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Saltz, Joel H.] Emory Univ, Ctr Comprehens Informat, Atlanta, GA 30322 USA.
RP Hersh, WR (reprint author), Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, BICC, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA.
EM hersh@ohsu.edu
RI Embi, Peter/E-3030-2011;
OI Hersh, William/0000-0002-4114-5148
FU AcademyHealth; NIH National Center for Advancing Translational Science
(NCATS) [5UL1RR024140, 8UL1TR000090, 1UL1RR024148, 5UL1RR025005,
2UL1RR024156, 5UL1RR025008]; NIH Clinical Center and National Library of
Medicine
FX Supported by a grant from AcademyHealth. Additional resources for author
time were provided by NIH National Center for Advancing Translational
Science (NCATS) Grants 5UL1RR024140 (W. R. H.), 8UL1TR000090 (P.J.E. and
P.R.O.P.), 1UL1RR024148 (E. V. B.), 5UL1RR025005 (H. P. L.),
2UL1RR024156 (G. H.), and 5UL1RR025008 (J.H.S.) as well as intramural
research funding from the NIH Clinical Center and National Library of
Medicine (J.J.C.).
NR 71
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U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0025-7079
EI 1537-1948
J9 MED CARE
JI Med. Care
PD AUG
PY 2013
VL 51
IS 8
SU 3
BP S30
EP S37
PG 8
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA AJ7ZQ
UT WOS:000337921600005
PM 23774517
ER
PT J
AU Patrick, H
Hennessy, E
McSpadden, K
Oh, A
AF Patrick, Heather
Hennessy, Erin
McSpadden, Kate
Oh, April
TI Parenting Styles and Practices in Children's Obesogenic Behaviors:
Scientific Gaps and Future Research Directions
SO CHILDHOOD OBESITY
LA English
DT Review
ID SELF-DETERMINATION THEORY; PHYSICAL-ACTIVITY; RESTRICTING ACCESS;
CONDITIONAL REGARD; AMERICAN MOTHERS; WEIGHT STATUS; OBESITY;
STRATEGIES; MOTIVATION; EPIDEMIOLOGY
AB Given the emerging global childhood obesity epidemic and the specter of a generation of children who will have a shorter life expectancy than that of their parents, recent research has focused on factors that influence children's weight status and obesogenic behaviors (i.e., eating, physical activity, and screen media use). Parents act as primary socializing agents for children, and thus growing evidence supports the role of parenting styles and practices in children's obesity-related behaviors and weight. Studying these processes in children and adolescents is important for several reasons. First, diet and physical activity behaviors and weight status track from childhood and adolescence into adulthood. Furthermore, diet and physical activity behaviors and weight status confer significant risk for cancer, diabetes, cardiovascular disease, and other chronic diseases. The purpose of this article is to describe the scientific gaps that need to be addressed to develop a more informed literature on parenting styles and practices in the domains of weight status and obesogenic behaviors, as identified by an expert panel assembled by the National Cancer Institute.
C1 [Patrick, Heather] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Hennessy, Erin] NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA.
[McSpadden, Kate] Catholic Univ Amer, Natl Cathol Sch Social Serv, Washington, DC 20064 USA.
[Oh, April] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA.
RP Patrick, H (reprint author), NCI, Div Canc Control & Populat Sci, Behav Res Program, Hlth Behav Res Branch, 9609 Med Ctr Dr,Room 3E112 MSC 9671, Bethesda, MD 20892 USA.
EM patrickha@mail.nih.gov
FU National Cancer Institute (NCI), National Institutes of Health
[HHSN261200800001E]; Cancer Prevention Fellowship Program; NCI; United
States Department of Agriculture/Agricultural Research Service [USDA/ARS
2012-68001-19285]; National Heart, Lung, and Blood Institute of the
National Institutes of Health [R13HL114262]
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute (NCI), 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 US Government. Erin
Hennessy is supported through a Cancer Research Training Award from the
Cancer Prevention Fellowship Program.; The authors wish to thank Linda
Nebeling, Chief, Health Behaviors Research Branch, Behavioral Research
Program, Division of Cancer Control and Population Sciences at the
National Cancer Institute for her scientific and administrative support
of the NCI-sponsored meeting on the role of parents in children's
cancer-preventive behaviors. We further wish to thank Michele Fisher,
Ashley Holmes, and Rebecca Roth for their assistance with meeting
logistic support. We would also like to thank the scientific experts who
participated in the NCI-sponsored meeting: Guadalupe Ayala, Nancy
Darling, Kirsten Davison, Jay Fagan, Jennifer Fisher, Wendy Grolnick,
Melanie Hingle, Eric Hodges, Sheryl Hughes, Jon Macy, Teresia O'Connor,
Tom Power, and Dianne Ward. We also thank Sheryl Hughes and Teresia
O'Connor for comments on an earlier draft of this manuscript.; We also
thank Tom Baranowski, Professor of Pediatrics at Baylor College of
Medicine, Children's Nutrition Research Center, and the planning
committee for the invitation to participate in the ISBNPA Pre-Conference
Workshop. The preconference to the 2012 International Society for
Behavioral Nutrition and Physical Activity (ISBNPA) annual meeting,
"Parenting Measurement: Current Status and Consensus Reports" and
resulting manuscripts were made possible due to funding from the United
States Department of Agriculture/Agricultural Research Service (USDA/ARS
2012-68001-19285) and the National Heart, Lung, and Blood Institute of
the National Institutes of Health (R13HL114262).
NR 67
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U1 6
U2 25
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 2153-2168
EI 2153-2176
J9 CHILD OBES
JI Child Obes.
PD AUG
PY 2013
VL 9
SU 1
BP S73
EP S86
DI 10.1089/chi.2013.0039
PG 14
WC Pediatrics
SC Pediatrics
GA AI4PL
UT WOS:000336847200008
PM 23944926
ER
PT J
AU Power, TG
Sleddens, EFC
Berge, J
Connell, L
Govig, B
Hennessy, E
Liggett, L
Mallan, K
Maria, DS
Odoms-Young, A
St George, SM
AF Power, Thomas G.
Sleddens, Ester F. C.
Berge, Jerica
Connell, Lauren
Govig, Bert
Hennessy, Erin
Liggett, Leanne
Mallan, Kimberley
Maria, Diane Santa
Odoms-Young, Angela
St George, Sara M.
TI Contemporary Research on Parenting: Conceptual, Methodological, and
Translational Issues
SO CHILDHOOD OBESITY
LA English
DT Article
ID FEEDING PRACTICES; VEGETABLE CONSUMPTION; NEGLECTED CONSTRUCT;
PRESCHOOL-CHILDREN; SOCIAL-DEVELOPMENT; CHILDHOOD OBESITY; WEIGHT
STATUS; BEHAVIOR; STYLES; ASSOCIATIONS
AB Researchers over the last decade have documented the association between general parenting style and numerous factors related to childhood obesity (e.g., children's eating behaviors, physical activity, and weight status). Many recent childhood obesity prevention programs are family focused and designed to modify parenting behaviors thought to contribute to childhood obesity risk. This article presents a brief consideration of conceptual, methodological, and translational issues that can inform future research on the role of parenting in childhood obesity. They include: (1) General versus domain specific parenting styles and practices; (2) the role of ethnicity and culture; (3) assessing bidirectional influences; (4) broadening assessments beyond the immediate family; (5) novel approaches to parenting measurement; and (6) designing effective interventions. Numerous directions for future research are offered.
C1 [Power, Thomas G.] Washington State Univ, Dept Human Dev, Pullman, WA 99164 USA.
[Sleddens, Ester F. C.] Maastricht Univ, Med Ctr, Dept Hlth Promot, NUTRIM Sch Nutr, Maastricht, Netherlands.
[Berge, Jerica] Univ Minnesota, Sch Med, Dept Family & Community Med, Minneapolis, MN 55455 USA.
[Connell, Lauren] Penn State Univ, Dept Biobehav Hlth, University Pk, PA 16802 USA.
[Govig, Bert] McGill Univ, Fac Med, Montreal, PQ, Canada.
[Hennessy, Erin] NCI, Canc Prevent Fellowship Program, Rockville, MD USA.
[Liggett, Leanne] Univ Otago, Dept Prevent & Social Med, Dunedin, New Zealand.
[Mallan, Kimberley] Queensland Univ Technol, Sch Exercise & Nutr Sci, Kelvin Grove, Australia.
[Connell, Lauren] Univ Texas Houston, Sch Nursing, Houston, TX USA.
[Odoms-Young, Angela] Univ Illinois, Dept Kinesiol & Nutr, Chicago, IL USA.
[St George, Sara M.] Univ S Carolina, Dept Psychol, Columbia, SC 29208 USA.
RP Power, TG (reprint author), Washington State Univ, Dept Human Dev, POB 644852, Pullman, WA 99164 USA.
EM tompower@wsu.edu
FU National Institutes of Child Health and Human Development [R01 HD062567,
K12 HD055887, F31 HD066944]; The National Institute of Food and
Agriculture [USDA 2011-68001-30009]; Netherlands Heart Foundation [2008
B112]; National Institute on Drug Abuse [T32DA017629-07]; Cancer
Research Training Award through Cancer Prevention Fellowship Program;
United States Department of Agriculture/Agricultural Research Service
[USDA/ARS 2012-68001-19285]; National Heart, Lung, and Blood Institute
of the National Institutes of Health [R13HL114262]
FX This article is a product of the Parenting Style Measurement Working
Group chaired by Ester Sleddens and Thomas Power at the ISBNPA 2012
Pre-Conference Workshop in Houston, Texas "Parenting Measurement:
Current Status and Consensus Reports." This work was supported in part
by the National Institutes of Child Health and Human Development grant
R01 HD062567 to Sheryl Hughes, The National Institute of Food and
Agriculture grant USDA 2011-68001-30009 to Sheryl Hughes, the
Netherlands Heart Foundation grant 2008 B112 to Ester Sleddens, the
National Institutes of Child Health and Human Development grant K12
HD055887 to Jerica Berge, a graduate fellowship from the National
Institute on Drug Abuse T32DA017629-07 to Lauren Connell, a Cancer
Research Training Award through the Cancer Prevention Fellowship Program
to Erin Hennessy, a Postdoctoral Research Fellowship supported by H.J.
Heinz to Kimberley Mallan, and a National Institutes of Child Health and
Human Development grant F31 HD066944 to Sarah St. George and Dawn
Wilson. The preconference to the 2012 International Society for
Behavioral Nutrition and Physical Activity (ISBNPA) annual meeting,
"Parenting Measurement: Current Status and Consensus Reports" and
resulting manuscripts were made possible due to funding from a United
States Department of Agriculture/Agricultural Research Service grant
USDA/ARS 2012-68001-19285 and a National Heart, Lung, and Blood
Institute of the National Institutes of Health grant R13HL114262 to
Thomas Baranowski.
NR 55
TC 17
Z9 17
U1 2
U2 13
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 2153-2168
EI 2153-2176
J9 CHILD OBES
JI Child Obes.
PD AUG
PY 2013
VL 9
SU 1
BP S87
EP S94
DI 10.1089/chi.2013.0038
PG 8
WC Pediatrics
SC Pediatrics
GA AI4PL
UT WOS:000336847200009
PM 23944927
ER
PT J
AU Collins, F
Beaudet, A
Draghia-Akli, R
Gruss, P
Savill, J
Syrota, A
Dautry, A
Ulfendahl, M
Walport, M
Onken, J
Glass, RI
AF Collins, Francis
Beaudet, Alain
Draghia-Akli, Ruxandra
Gruss, Peter
Savill, John
Syrota, Andre
Dautry, Alice
Ulfendahl, Mats
Walport, Mark
Onken, James
Glass, Roger I.
TI A database on global health research in Africa
SO LANCET GLOBAL HEALTH
LA English
DT Editorial Material
C1 [Collins, Francis; Onken, James] NIH, Off Director, Bethesda, MD 20892 USA.
[Beaudet, Alain] Canadian Inst Hlth Res, Ottawa, ON, Canada.
[Draghia-Akli, Ruxandra] Commiss European Communities, B-1049 Brussels, Belgium.
[Gruss, Peter] Max Planck Gesell, Munich, Germany.
[Savill, John] MRC, London, England.
[Syrota, Andre] INSERM, Paris, France.
[Dautry, Alice] Inst Pasteur, Paris, France.
[Ulfendahl, Mats] Swedish Res Council, Stockholm, Sweden.
[Walport, Mark] Wellcome Trust Res Labs, London, England.
[Glass, Roger I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Collins, F (reprint author), NIH, Off Director, Bldg 10, Bethesda, MD 20892 USA.
EM glassr@mail.nih.gov
OI Walport, Mark/0000-0001-7220-5273
NR 2
TC 5
Z9 5
U1 0
U2 4
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2214-109X
J9 LANCET GLOB HEALTH
JI Lancet Glob. Health
PD AUG
PY 2013
VL 1
IS 2
BP E64
EP E65
DI 10.1016/S2214-109X(13)70012-3
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AH8XV
UT WOS:000336422400006
PM 25104151
ER
PT J
AU Noel-Brune, M
Goldizen, FC
Neira, M
van den Berg, M
Lewis, N
King, M
Suk, WA
Carpenter, DO
Arnold, RG
Sly, PD
AF Noel-Brune, Marie
Goldizen, Fiona C.
Neira, Maria
van den Berg, Martin
Lewis, Nancy
King, Malcolm
Suk, William A.
Carpenter, David O.
Arnold, Robert G.
Sly, Peter D.
TI Health effects of exposure to e-waste
SO LANCET GLOBAL HEALTH
LA English
DT Letter
C1 [Noel-Brune, Marie; Neira, Maria] WHO, Dept Publ Hlth & Environm, CH-1211 Geneva, Switzerland.
[Goldizen, Fiona C.; Sly, Peter D.] Univ Queensland, Queensland Childrens Med Res Inst, Childrens Hlth & Environm Program, Brisbane, Qld 4029, Australia.
[van den Berg, Martin] Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands.
[Lewis, Nancy] East West Ctr, Honolulu, HI USA.
[King, Malcolm] Simon Fraser Univ, Inst Aboriginal Peoples Hlth, Canadian Inst Hlth Res, Burnaby, BC V5A 1S6, Canada.
[Suk, William A.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA.
[Carpenter, David O.] Univ Albany, Inst Hlth & Environm, Rensselaer, NY USA.
[Arnold, Robert G.] Univ Arizona, Chem & Environm Engn Dept, Tucson, AZ USA.
RP Noel-Brune, M (reprint author), WHO, Dept Publ Hlth & Environm, CH-1211 Geneva, Switzerland.
EM p.sly@uq.edu.au
OI Sly, Peter/0000-0001-6305-2201
NR 5
TC 4
Z9 4
U1 1
U2 8
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2214-109X
J9 LANCET GLOB HEALTH
JI Lancet Glob. Health
PD AUG
PY 2013
VL 1
IS 2
BP E70
EP E70
DI 10.1016/S2214-109X(13)70020-2
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AH8XV
UT WOS:000336422400010
PM 25104155
ER
PT J
AU Yamshchikov, GV
Schmid, GP
AF Yamshchikov, Galina V.
Schmid, George P.
TI Publication practices and attitudes towards evidence-based medicine in
central Asia
SO LANCET GLOBAL HEALTH
LA English
DT Letter
C1 [Schmid, George P.] Ctr Dis Control & Prevent, Alma Ata, Kazakhstan.
[Yamshchikov, Galina V.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Yamshchikov, GV (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM gps1@cdc.gov
FU Intramural CDC HHS [CC999999]
NR 4
TC 1
Z9 1
U1 0
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2214-109X
J9 LANCET GLOB HEALTH
JI Lancet Glob. Health
PD AUG
PY 2013
VL 1
IS 2
BP E73
EP E74
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AH8XV
UT WOS:000336422400013
PM 25104158
ER
PT J
AU Antignani, A
FitzGerald, D
AF Antignani, Antonella
FitzGerald, David
TI Immunotoxins: The Role of the Toxin
SO TOXINS
LA English
DT Review
DE immunotoxin; antibody; toxin; cancer; immunotherapy; apoptosis;
translocation; ricin; diphtheria; Pseudomonas
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; BONE-MARROW-TRANSPLANTATION; HAIRY-CELL
LEUKEMIA; PHASE-II TRIAL; RIBOSOME-INACTIVATING PROTEINS; SINGLE-CHAIN
IMMUNOTOXINS; NON-HODGKINS-LYMPHOMA; VERSUS-HOST-DISEASE;
DIPHTHERIA-TOXIN; RECOMBINANT IMMUNOTOXIN
AB Immunotoxins are antibody-toxin bifunctional molecules that rely on intracellular toxin action to kill target cells. Target specificity is determined via the binding attributes of the chosen antibody. Mostly, but not exclusively, immunotoxins are purpose-built to kill cancer cells as part of novel treatment approaches. Other applications for immunotoxins include immune regulation and the treatment of viral or parasitic diseases. Here we discuss the utility of protein toxins, of both bacterial and plant origin, joined to antibodies for targeting cancer cells. Finally, while clinical goals are focused on the development of novel cancer treatments, much has been learned about toxin action and intracellular pathways. Thus toxins are considered both medicines for treating human disease and probes of cellular function.
C1 [Antignani, Antonella; FitzGerald, David] NCI, Biotherapy Sect, Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Antignani, A (reprint author), NCI, Biotherapy Sect, Mol Biol Lab, Ctr Canc Res, 37 Convent Dr, Bethesda, MD 20892 USA.
EM antignaa@mail.nih.gov; fitzgerd@helix.nih.gov
FU Intramural Research Program, National Cancer Institute, Center for
Cancer Research at the National Institutes of Health, Department of
Health and Human Services
FX This research was supported by funding from the Intramural Research
Program, National Cancer Institute, Center for Cancer Research at the
National Institutes of Health, Department of Health and Human Services.
The authors also acknowledge the many contributions of their colleagues
at the Laboratory of Molecular Biology.
NR 111
TC 39
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U1 5
U2 15
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 2072-6651
J9 TOXINS
JI Toxins
PD AUG
PY 2013
VL 5
IS 8
BP 1486
EP 1502
DI 10.3390/toxins5081486
PG 17
WC Toxicology
SC Toxicology
GA AC9CK
UT WOS:000332831500012
PM 23965432
ER
PT J
AU Grange, LK
Jacobs-El, N
Wiley, HE
Kurup, S
Chan, CC
Sen, HN
AF Grange, Landon K.
Jacobs-El, Naima
Wiley, Henry E.
Kurup, Shree
Chan, Chi-Chao
Sen, H. Nida
TI Intraocular (vitreoretinal) lymphoma following primary testicular
lymphoma
SO CANADIAN JOURNAL OF OPHTHALMOLOGY-JOURNAL CANADIEN D OPHTALMOLOGIE
LA English
DT Letter
C1 [Grange, Landon K.; Jacobs-El, Naima; Wiley, Henry E.; Chan, Chi-Chao; Sen, H. Nida] NEI, NIH, Bethesda, MD 20892 USA.
[Kurup, Shree] Wake Forest Univ, Winston Salem, NC 27109 USA.
RP Sen, HN (reprint author), NEI, NIH, Bethesda, MD 20892 USA.
EM senh@nei.nih.gov
NR 5
TC 0
Z9 0
U1 0
U2 1
PU CANADIAN OPHTHAL SOC
PI OTTAWA
PA 1525 CARLING AVE SUITE 610, OTTAWA, ONTARIO K1Z 8R9, CANADA
SN 0008-4182
EI 1715-3360
J9 CAN J OPHTHALMOL
JI Can. J. Opthalmol.-J. Can. Opthalmol.
PD AUG
PY 2013
VL 48
IS 4
BP E95
EP E97
DI 10.1016/j.jcjo.2013.03.024
PG 4
WC Ophthalmology
SC Ophthalmology
GA AA5OI
UT WOS:000331148900017
PM 23931497
ER
PT J
AU Brown, DS
Jia, HM
Zack, MM
Thompson, WW
Haddix, AC
Kaplan, RM
AF Brown, Derek S.
Jia, Haomiao
Zack, Matthew M.
Thompson, William W.
Haddix, Anne C.
Kaplan, Robert M.
TI Using health-related quality of life and quality-adjusted life
expectancy for effective public health surveillance and prevention
SO EXPERT REVIEW OF PHARMACOECONOMICS & OUTCOMES RESEARCH
LA English
DT Editorial Material
DE chronic disease burden; life expectancy; prevention; quality of life;
surveillance
ID UNITED-STATES; SMOKING; SAMPLE
C1 [Brown, Derek S.] Washington Univ, Inst Publ Hlth, St Louis, MO 63130 USA.
[Jia, Haomiao] Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY 10027 USA.
[Jia, Haomiao] Columbia Univ, Sch Nursing, New York, NY 10027 USA.
[Zack, Matthew M.; Thompson, William W.; Haddix, Anne C.] US Ctr Dis Control & Prevent, Div Populat Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA.
[Kaplan, Robert M.] NIH, Bethesda, MD USA.
RP Brown, DS (reprint author), Washington Univ, Inst Publ Hlth, Campus Box 1196,One Brookings Dr, St Louis, MO 63130 USA.
EM dereksbrown@wustl.edu
RI Brown, Derek/J-3035-2013
OI Brown, Derek/0000-0001-9908-9882
NR 19
TC 7
Z9 7
U1 0
U2 2
PU EXPERT REVIEWS
PI LONDON
PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB,
ENGLAND
SN 1473-7167
EI 1744-8379
J9 EXPERT REV PHARM OUT
JI Expert Rev. Pharmacoecon. Outcomes Res.
PD AUG
PY 2013
VL 13
IS 4
BP 425
EP 427
DI 10.1586/14737167.2013.818816
PG 3
WC Health Care Sciences & Services; Health Policy & Services; Pharmacology
& Pharmacy
SC Health Care Sciences & Services; Pharmacology & Pharmacy
GA 301ME
UT WOS:000330535600003
PM 23977969
ER
PT J
AU Maskew, M
MacPhail, AP
Whitby, D
Egger, M
Fox, MP
AF Maskew, Mhairi
MacPhail, A. Patrick
Whitby, Denise
Egger, Matthias
Fox, Matthew P.
TI Kaposi Sarcoma-Associated Herpes Virus and Response to Antiretroviral
Therapy: A Prospective Study of HIV-Infected Adults
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE Kaposi sarcoma herpes virus; antiretroviral therapy; resource-poor
setting; virologic suppression
ID SUB-SAHARAN AFRICA; HUMAN-HERPESVIRUS-8 INFECTION; GENERAL-POPULATION;
DNA-SEQUENCES; SOUTH-AFRICA; FOLLOW-UP; PROGRESSION; REPLICATION; CELLS;
WOMEN
AB Background: The possible impact of coinfection with the Kaposi sarcoma-associated herpes virus (KSHV) on the response to antiretroviral therapy (ART) is unknown. Prospective studies are rare, particularly in Africa.
Methods: We enrolled a prospective cohort of HIV-infected adults initiating ART in Johannesburg, South Africa. The subjects were defined as seropositive to KSHV if they were reactive to either KSHV lytic K8.1 or latent Orf73 antigen or to both. The subjects were followed from ART initiation until 18 months of treatment. HIV viral load and CD4 counts were tested 6 monthly. Linear generalized estimating and log-binomial regression models were used to estimate the effect of KSHV infection on immunologic recovery and response and HIV viral load suppression within 18 months after ART initiation.
Results: Three hundred eighty-five subjects initiating ART from November 2008 to March 2009 were considered to be eligible including 184 (48%) KSHV+. The KSHV+ group was similar to the KSHV- in terms of age, gender, initiating CD4 count, body mass index, tuberculosis, and hemoglobin levels. The KSHV+ group gained a similar number of cells at 6 [difference of 10 cells per cubic millimeter, 95% confidence interval (CI): -11 to 31], 12 (3 cells per cubic millimeter, 95% CI: -19 to 25), and 18 months (24 cells per cubic millimeter, 95% CI: -13 to 61) compared with that gained by the KSHV- group. Adjusted relative risk of failure to suppress viral load to <400 copies per milliliter (1.03; 95% CI: 0.90 to 1.17) were similar for KSHV+ and KSHV- by 6 months on treatment.
Conclusions: In a population with a high KSHV prevalence, HIV-positive adults coinfected with KSHV achieved similar immunologic and virologic responses to ART early after treatment initiation compared with those with KSHV-.
C1 [Maskew, Mhairi; Fox, Matthew P.] Univ Witwatersrand, Fac Hlth Sci, Sch Clin Med, Hlth Econ & Epidemiol Res Off,Dept Internal Med, Johannesburg, South Africa.
[MacPhail, A. Patrick] Univ Witwatersrand, Fac Hlth Sci, Sch Clin Med, Clin HIV Res Unit,Dept Internal Med, Johannesburg, South Africa.
[Whitby, Denise] SAIC Frederick, Frederick Natl Lab Canc Res, AIDS & Canc Virus Program, Viral Oncol Sect, Frederick, MD USA.
[Egger, Matthias] Univ Bern, Inst Social & Prevent Med, Bern, Switzerland.
[Fox, Matthew P.] Ctr Global Hlth & Dev, Boston, MA USA.
[Fox, Matthew P.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
RP Maskew, M (reprint author), Helen Joseph Hosp, Themba Lethu Clin, Hlth Econ & Epidemiol Res Off, Perth Rd, ZA-2192 Johannesburg, South Africa.
EM mmaskew@heroza.org
FU National Institute of Allergy and Infectious Diseases (NIAID)
[5U01-AI069924-05]; United States Agency for International Development
(USAID) [674-A-12-00,029]; NIH
FX Supported by the National Institute of Allergy and Infectious Diseases
(NIAID), Grant 5U01-AI069924-05 to the International epidemiological
Databases to Evaluate AIDS in Southern Africa (IeDEA-SA). This study was
also made possible by the generous support of the American people
through Cooperative Agreement AID 674-A-12-00,029 from the United States
Agency for International Development (USAID). M. M., M. F., M. E., and
D. W. also receive funding from the NIH.
NR 41
TC 5
Z9 5
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD AUG 1
PY 2013
VL 63
IS 4
BP 442
EP 448
PG 7
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 300FF
UT WOS:000330449100008
PM 23614996
ER
PT J
AU Herold, BC
Keller, MJ
Shi, QH
Hoover, DR
Carpenter, CA
Huber, A
Parikh, UM
Agnew, KJ
Minkoff, H
Colie, C
Nowicki, MJ
D'Souza, G
Watts, DH
Anastos, K
AF Herold, Betsy C.
Keller, Marla J.
Shi, Qiuhu
Hoover, Donald R.
Carpenter, Colleen A.
Huber, Ashley
Parikh, Urvi M.
Agnew, Kathy J.
Minkoff, Howard
Colie, Christine
Nowicki, Marek J.
D'Souza, Gypsyamber
Watts, D. Heather
Anastos, Kathryn
TI Plasma and Mucosal HIV Viral Loads Are Associated With Genital Tract
Inflammation in HIV-Infected Women
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE HIV; HSV; mucosal immunity; inflammation; female genital tract; WIHS
ID LEUKOCYTE PROTEASE INHIBITOR; IMMUNODEFICIENCY-VIRUS TYPE-1; ACTIVE
ANTIRETROVIRAL THERAPY; BACTERIAL VAGINOSIS; ALPHA-DEFENSINS; DISEASE
PROGRESSION; CIGARETTE-SMOKING; ANTI-HIV-1 ACTIVITY; IMMUNE MEDIATORS;
INTERAGENCY HIV
AB Background: Systemic and mucosal inflammation may play a role in HIV control. A cross-sectional comparison was conducted among women in the Women's Interagency HIV Study to explore the hypothesis that compared with HIV-uninfected participants, women with HIV, and, in particular, those with high plasma viral load (PVL) have increased levels of mucosal and systemic inflammatory mediators and impaired mucosal endogenous antimicrobial activity.
Methods: Nineteen HIV-uninfected, 40 HIV-infected on antiretroviral therapy (ART) with PVL <= 2600 copies/mL (low viral load) (HIV+-LVL), and 19 HIV-infected on or off ART with PVL > 10,000 (high viral load) (HIV+-HVL) were evaluated. Immune mediators and viral RNA were quantified in plasma and cervicovaginal lavage (CVL). The CVL antimicrobial activity was also determined.
Results: Compared to HIV-uninfected participants, HIV+-HVL women had higher levels of mucosal but not systemic proinflammatory cytokines and chemokines, higher Nugent scores, and lower Escherichia coli bactericidal activity. In contrast, there were no significant differences between HIV+-LVL and HIV-uninfected controls. After adjusting for PVL, HIV genital tract shedding was significantly associated with higher CVL concentrations of IL-6, IL-1 beta, MIP-1 alpha, and CCL5 (RANTES) and higher plasma concentrations of MIP-1 alpha. High PVL was associated with higher CVL levels of IL-1 beta and RANTES, as well as with higher Nugent scores, lower E. coli bactericidal activity, smoking, and lower CD4 counts; smoking and CD4 count retained statistical significance in a multivariate model.
Conclusions: Further study is needed to determine if the relationship between mucosal inflammation and PVL is causal and to determine if reducing mucosal inflammation is beneficial.
C1 [Herold, Betsy C.; Carpenter, Colleen A.; Huber, Ashley] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10461 USA.
[Herold, Betsy C.; Anastos, Kathryn] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Obstet & Gynecol & Womens Hlth, Bronx, NY 10461 USA.
[Herold, Betsy C.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA.
[Anastos, Kathryn] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA.
[Shi, Qiuhu] New York Med Coll, Valhalla, NY 10595 USA.
[Hoover, Donald R.] Rutgers State Univ, Inst Hlth Hlth Care Policy & Aging Res, Piscataway, NJ USA.
[Parikh, Urvi M.] Univ Pittsburgh, Pittsburgh, PA USA.
[Agnew, Kathy J.] Univ Washington, Seattle, WA 98195 USA.
[Minkoff, Howard] Maimonides Hosp, Brooklyn, NY 11219 USA.
[Colie, Christine] Georgetown Univ, Med Ctr, Washington, DC 20007 USA.
[Nowicki, Marek J.] Univ So Calif, Los Angeles, CA USA.
[D'Souza, Gypsyamber] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Watts, D. Heather] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, NIH, Bethesda, MD USA.
[Anastos, Kathryn] Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA.
RP Herold, BC (reprint author), Montefiore Med Ctr, Albert Einstein Coll Med, Dept Pediat, 1300 Morris Pk Ave,Forchheimer 702, Bronx, NY 10461 USA.
EM betsy.herold@einstein.yu.edu
FU National Institute of Allergy and Infectious Diseases [UO1-AI-35004,
UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590];
Eunice Kennedy Shriver National Institute of Child Health and Human
Development [UO1-HD-32632]; Center for AIDS Research at the Albert
Einstein College of Medicine and Montefiore Medical Center [NIH
AI-51519]; [U19AI067980]; [R01AI065309]; [R33AI079763]
FX The Women's Interagency HIV Study (WIHS) is supported by the National
Institute of Allergy and Infectious Diseases Grants UO1-AI-35004,
UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590
and by the Eunice Kennedy Shriver National Institute of Child Health and
Human Development Grant UO1-HD-32632. The study was also supported in
part by Grants U19AI067980, R01AI065309, R33AI079763 and the Center for
AIDS Research at the Albert Einstein College of Medicine and Montefiore
Medical Center Grant NIH AI-51519. The contents of this publication are
solely the responsibility of the authors and do not necessarily
represent the official views of the National Institutes of Health.
NR 52
TC 13
Z9 13
U1 2
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD AUG 1
PY 2013
VL 63
IS 4
BP 485
EP 493
PG 9
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 300FF
UT WOS:000330449100014
PM 23591635
ER
PT J
AU Succi, RCM
Krauss, MR
Harris, DR
Machado, DM
de Moraes-Pinto, MI
Mussi-Pinhata, MM
Ruz, NP
Pierre, RB
Kolevic, L
Joao, E
Foradori, I
Hazra, R
Siberry, GK
AF Succi, Regina C. M.
Krauss, Margot R.
Harris, D. Robert
Machado, Daisy M.
de Moraes-Pinto, Maria Isabel
Mussi-Pinhata, Marisa M.
Pavia Ruz, Noris
Pierre, Russell B.
Kolevic, Lenka
Joao, Esau
Foradori, Irene
Hazra, Rohan
Siberry, George K.
CA NISDI Pediat Study Grp 2012
TI Undervaccination of Perinatally HIV-infected and HIV-exposed Uninfected
Children in Latin America and the Caribbean
SO PEDIATRIC INFECTIOUS DISEASE JOURNAL
LA English
DT Article
DE pediatric HIV infection; vaccination; Latin America
ID HUMAN-IMMUNODEFICIENCY-VIRUS; PARALYTIC POLIOMYELITIS; IMMUNIZATION
COVERAGE; VACCINE; COHORT; SAFETY; RISK; BORN
AB Background: Perinatally HIV-infected (PHIV) children may be at risk of undervaccination. Vaccination coverage rates among PHIV and HIV-exposed uninfected (HEU) children in Latin America and the Caribbean were compared.
Methods: All PHIV and HEU children born from 2002 to 2007 who were enrolled in a multisite observational study conducted in Latin America and the Caribbean were included in this analysis. Children were classified as up to date if they had received the recommended number of doses of each vaccine at the appropriate intervals by 12 and 24 months of age. Fisher's exact test was used to analyze the data. Covariates potentially associated with a child's HIV status were considered in multivariable logistic regression modeling.
Results: Of 1156 eligible children, 768 (66.4%) were HEU and 388 (33.6%) were PHIV. HEU children were significantly (P < 0.01) more likely to be up to date by 12 and 24 months of age for all vaccines examined. Statistically significant differences persisted when the analyses were limited to children enrolled before 12 months of age. Controlling for birth weight, sex, primary caregiver education and any use of tobacco, alcohol or illegal drugs during pregnancy did not contribute significantly to the logistic regression models.
Conclusions: PHIV children were significantly less likely than HEU children to be up to date for their childhood vaccinations at 12 and 24 months of age, even when limited to children enrolled before 12 months of age. Strategies to increase vaccination rates in PHIV are needed.
C1 [Succi, Regina C. M.; Machado, Daisy M.; de Moraes-Pinto, Maria Isabel] Univ Fed Sao Paulo, UNIFESP, Escola Paulista Med, Sao Paulo, Brazil.
[Krauss, Margot R.; Harris, D. Robert] Westat Corp, Rockville, MD USA.
[Mussi-Pinhata, Marisa M.] Univ Sao Paulo, Fac Med Ribeirao Preto, BR-14049 Ribeirao Preto, Brazil.
[Pavia Ruz, Noris] Hosp Infantil Mexico Dr Federico Gomez, Depto Infectol, Clin Inmunodeficiencias, Mexico City, DF, Mexico.
[Pierre, Russell B.] Univ W Indies, Dept Child & Adolescent Hlth, Kingston, Jamaica.
[Kolevic, Lenka] Natl Univ San Marcos Lima, Natl Inst Child Hlth, Lima, Peru.
[Kolevic, Lenka] Natl Univ San Marcos Lima, Fac Med, Lima, Peru.
[Joao, Esau] Hosp Fed Servidores Estado, Rio De Janeiro, Brazil.
[Foradori, Irene] Univ Buenos Aires, Fac Med, Buenos Aires, DF, Argentina.
[Hazra, Rohan; Siberry, George K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal & Pediat Infect Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Siberry, GK (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, NIH, 6100 Execut Blvd,Room 4B11H, Bethesda, MD 20892 USA.
EM siberryg@mail.nih.gov
FU NICHD [N01-HD-3-3345, HHSN267200800001C, N01-HD-8-0001]
FX Supported by NICHD Contract #N01-HD-3-3345 (2002 to 2007) and by NICHD
Contract # HHSN267200800001C (NICHD Control # N01-HD-8-0001) (2007 to
2012). The authors have no other funding or conflicts of interest to
disclose.
NR 23
TC 3
Z9 3
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0891-3668
EI 1532-0987
J9 PEDIATR INFECT DIS J
JI Pediatr. Infect. Dis. J.
PD AUG
PY 2013
VL 32
IS 8
BP 845
EP 850
DI 10.1097/INF.0b013e31828bbe68
PG 6
WC Immunology; Infectious Diseases; Pediatrics
SC Immunology; Infectious Diseases; Pediatrics
GA 301HT
UT WOS:000330524100013
PM 23860480
ER
PT J
AU Moon, SS
Tate, JE
Ray, P
Dennehy, PH
Archary, D
Coutsoudis, A
Bland, R
Newell, ML
Glass, RI
Parashar, U
Jiang, BM
AF Moon, Sung-Sil
Tate, Jacqueline E.
Ray, Pratima
Dennehy, Penelope H.
Archary, Derseree
Coutsoudis, Anna
Bland, Ruth
Newell, Marie-Louise
Glass, Roger I.
Parashar, Umesh
Jiang, Baoming
TI Differential Profiles and Inhibitory Effect on Rotavirus Vaccines of
Nonantibody Components in Breast Milk From Mothers in Developing and
Developed Countries
SO PEDIATRIC INFECTIOUS DISEASE JOURNAL
LA English
DT Article
DE rotavirus; breastmilk; lactoferrin; lactadherin; vaccine
ID EFFICACY; INFANTS; IMMUNOGENICITY; SAFETY; INFECTION; CHILDREN;
GASTROENTERITIS; METAANALYSIS; LACTOFERRIN; PROTECTION
AB Background: Live oral rotavirus vaccines have been less immunogenic and efficacious for children of developing countries than for those in middle income and industrialized countries, and the basis for these differences is not fully understood. Recently, we demonstrated that breastmilk from mothers in India had significantly higher IgA and neutralizing activity against rotavirus that could reduce the effective titer of rotavirus vaccines reaching the gut when compared with that from mothers in the United States. We extended our study to understand the specific contribution of those nonantibody components in breastmilk to the neutralizing activity against rotavirus vaccine we observed.
Methods: Breastmilk samples were collected from mothers of breast-feeding infants aged between 4 and 29 weeks (ie, vaccine eligible age) in India (N = 40), South Africa (N = 50) and the United States (N = 51). We examined breastmilk for lactoferrin, lactadherin, rotavirus-specific IgA and neutralizing activity against 3 rotavirus vaccine strains (Rotarix, RotaTeq G1 and 116E) using enzyme immunoassays, a plaque reduction assay or a microneutralization assay.
Results: We observed higher levels of lactoferrin, lactadherin, IgA and neutralizing activity in breastmilk specimens from Indian and South African women than those from American women. We demonstrated positive associations between levels of lactoferrin or IgA and neutralizing activity in Indian and South African specimens, but not in American specimens. We demonstrated that the inhibitory effect of lactoferrin was dose- or species-dependent, as evidenced by greater reduction in titer of Rotarix and 116E by human lactoferrin. Lactadherin also exhibited inhibitory activity to rotavirus vaccines but appeared to be less effective.
Conclusions: The lower immunogenicity and efficacy of rotavirus vaccines in developing countries could be explained, in part, by synergistic inhibitory effect of high levels of antibody and nonantibody components in breastmilk consumed by infants at the time of immunization. Therefore, there is a need for alternative rotavirus vaccine strategies in breast-feeding populations.
C1 [Moon, Sung-Sil; Tate, Jacqueline E.; Parashar, Umesh; Jiang, Baoming] Ctr Dis Control & Prevent, Div Viral Dis, Atlanta, GA USA.
[Ray, Pratima] All India Inst Med Sci, Dept Pediat, Delhi, India.
[Dennehy, Penelope H.] Rhode Isl Hosp, Dept Pediat, Providence, RI USA.
[Archary, Derseree; Coutsoudis, Anna] Univ KwaZulu Natal, Dept Pediat & Child Hlth, Durban, South Africa.
[Archary, Derseree] Univ KwaZulu Natal, Ctr AIDS Program Res South Africa, Durban, South Africa.
[Bland, Ruth; Newell, Marie-Louise] Univ KwaZulu Natal, Africa Ctr Populat & Hlth Studies, Somkhele, South Africa.
[Bland, Ruth] Univ Glasgow, Sch Med, Glasgow G12 8QQ, Lanark, Scotland.
[Newell, Marie-Louise] UCL, Inst Child Hlth, London WC1E 6BT, England.
[Glass, Roger I.] NIH, Fogarty Int Ctr, Rockville, MD USA.
RP Jiang, BM (reprint author), Natl Ctr Immunizat & Resp Dis, Gastroenteritis & Resp Viruses Lab Branch, MS G04,1600 Clifton Rd NE, Atlanta, GA 30333 USA.
EM bxj4@cdc.gov
OI Dennehy, Penelope/0000-0002-2259-5370; Ray, Pratima/0000-0002-2182-2279;
Newell, Marie-Louise/0000-0002-1074-7699
FU Intramural CDC HHS [CC999999]; Wellcome Trust [097410]
NR 31
TC 16
Z9 16
U1 1
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0891-3668
EI 1532-0987
J9 PEDIATR INFECT DIS J
JI Pediatr. Infect. Dis. J.
PD AUG
PY 2013
VL 32
IS 8
BP 863
EP 870
DI 10.1097/INF.0b013e318290646d
PG 8
WC Immunology; Infectious Diseases; Pediatrics
SC Immunology; Infectious Diseases; Pediatrics
GA 301HT
UT WOS:000330524100016
PM 23584581
ER
PT J
AU Horton, JA
Li, F
Chung, EJ
Hudak, K
White, A
Krausz, K
Gonzalez, F
Citrin, D
AF Horton, Jason A.
Li, Fei
Chung, Eun Joo
Hudak, Kathryn
White, Ayla
Krausz, Kristopher
Gonzalez, Frank
Citrin, Deborah
TI Quercetin Inhibits Radiation-Induced Skin Fibrosis
SO RADIATION RESEARCH
LA English
DT Article
ID TRANSFORMING GROWTH-FACTOR-BETA-1; IN-VITRO; GROWTH; METABOLOMICS;
EXPRESSION; FLAVONOIDS; MICE; MYOFIBROBLASTS; GLUCURONIDES; FIBROBLASTS
AB Radiation induced fibrosis of the skin is a late toxicity that may result in loss of function due to reduced range of motion and pain. The current study sought to determine if oral delivery of quercetin mitigates radiation-induced cutaneous injury. Female C3H/HeN mice were fed control chow or quercetin-formulated chow (1% by weight). The right hind leg was exposed to 35 Gy of X rays and the mice were followed serially to assess acute toxicity and hind leg extension. Tissue samples were collected for assessment of soluble collagen and tissue cytokines. Human and murine fibroblasts were subjected to clonogenic assays to determine the effects of quercetin on radiation response. Contractility of fibroblasts was assessed with a collagen contraction assay in the presence or absence of quercetin and transforming growth factor-beta (TGF-beta). Western blotting of proteins involved in fibroblast contractility and TGF-beta signaling were performed. Quercetin treatment significantly reduced hind limb contracture, collagen accumulation and expression of TGF-beta in irradiated skin. Quercetin had no effect on the radioresponse of fibroblasts or murine tumors, but was capable of reducing the contractility of fibroblasts in response to TGF-beta, an effect that correlated with partial stabilization of phosphorylated cofilin. Quercetin is capable of mitigating radiation induced skin fibrosis and should be further explored as a therapy for radiation fibrosis. (C) 2013 by Radiation Research Society
C1 [Horton, Jason A.; Chung, Eun Joo; Hudak, Kathryn; White, Ayla; Citrin, Deborah] NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA.
[Li, Fei; Krausz, Kristopher; Gonzalez, Frank] NCI, Lab Metab, Bethesda, MD 20892 USA.
RP Citrin, D (reprint author), NCI, Radiat Oncol Branch, CCR, 10-CRC Hatfield Clin Res Ctr,B2-3500, Bethesda, MD 20892 USA.
EM citrind@mail.nih.gov
RI Li, Fei/F-6849-2013
FU Intramural Research Program of the NIH, NCI
FX This research was supported by the Intramural Research Program of the
NIH, NCI.
NR 33
TC 9
Z9 11
U1 1
U2 13
PU RADIATION RESEARCH SOC
PI LAWRENCE
PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA
SN 0033-7587
EI 1938-5404
J9 RADIAT RES
JI Radiat. Res.
PD AUG
PY 2013
VL 180
IS 2
BP 205
EP 215
DI 10.1667/RR3237.1
PG 11
WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology,
Nuclear Medicine & Medical Imaging
GA AA3KG
UT WOS:000330990700010
PM 23819596
ER
PT J
AU Deshpande, N
Metter, EJ
Guralnik, J
Ferrucci, L
AF Deshpande, Nandini
Metter, E. Jeffrey
Guralnik, Jack
Ferrucci, Luigi
TI Can Failure on Adaptive Locomotor Tasks Independently Predict Incident
Mobility Disability?
SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION
LA English
DT Article
DE Mobility; Disability; Aging
ID OLDER-ADULTS; COMMUNITY MOBILITY; WALKING; BALANCE; PERFORMANCE;
CHALLENGES; DIFFICULTY; INCHIANTI; EXERCISE; DECLINE
AB This study examined whether inability to perform adaptive locomotor tests predicts self-reported incident mobility disability. InCHIANTI study participants (N = 611; age, 50-85 yrs) who could walk 7 m at self-selected speed and who had no self-reported mobility disability at baseline were included. The ability to complete four adaptive locomotor tests was assessed: fast walking, walking on a narrow path, crossing obstacles while walking, and talking while walking. Mobility disability was recorded again at 3-yr follow-up. Failure in the fast-walking and narrow-path walking tests predicted approximately 2.5 times likelihood of reporting incident mobility disability (P = 0.009 and P = 0.011, respectively). Failure in the obstacle-crossing test predicted approximately two times likelihood of reporting incident mobility disability; however, this result did not reach statistical significance (P = 0.077). Failure in talking while walking did not predict incident mobility disability. Those who failed both the fast-walking and narrow-path walking tests were almost nine times as likely to report incident mobility disability.
C1 [Deshpande, Nandini] Queens Univ, Sch Rehabil Therapy, Kingston, ON K7L 3N6, Canada.
[Metter, E. Jeffrey; Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA.
[Guralnik, Jack] Univ Maryland, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA.
RP Deshpande, N (reprint author), Queens Univ, Sch Rehabil Therapy, 31 George St, Kingston, ON K7L 3N6, Canada.
FU Italian Ministry of Health [ICS 110.1\RS97.71]; National Institute on
Aging [N01-AG-916413, N01-AG-821336, N01-AG-5-0002, R01 AG027012];
National Institute on Aging, National Institutes of Health
FX The InCHIANTI study was supported as a "targeted project" (ICS
110.1\RS97.71) by the Italian Ministry of Health and, in part, by
National Institute on Aging contracts N01-AG-916413, N01-AG-821336, and
N01-AG-5-0002 and National Institute on Aging grant R01 AG027012 and the
Intramural Research Program, National Institute on Aging, National
Institutes of Health. Presented, in part, at the meeting of the
International Society for Posture and Gait Research Conference, Norway,
June 2012. Financial disclosure statements have been obtained, and no
conflicts of interest have been reported by the authors or by any
individuals in control of the content of this article.
NR 27
TC 0
Z9 0
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0894-9115
EI 1537-7385
J9 AM J PHYS MED REHAB
JI Am. J. Phys. Med. Rehabil.
PD AUG
PY 2013
VL 92
IS 8
BP 704
EP 709
DI 10.1097/PHM.0b013e31827d634e
PG 6
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 299CS
UT WOS:000330373300007
PM 23291600
ER
PT J
AU Carney, JA
Stratakis, CA
Young, WF
AF Carney, J. Aidan
Stratakis, Constantine A.
Young, William F., Jr.
TI Adrenal Cortical Adenoma The Fourth Component of the Carney Triad and an
Association With Subclinical Cushing Syndrome
SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE adrenal; Carney triad; adrenocortical adenoma; Cushing syndrome
ID GASTROINTESTINAL STROMAL TUMORS; PULMONARY CHONDROMA; CARNEY TRIAD;
CUSHING-SYNDROME; PARAGANGLIOMA; HYPERPLASIA; MUTATIONS; DISEASE; UPDATE
AB The Carney triad is the combination of gastric stromal sarcoma, pulmonary chondroma, and extra-adrenal paraganglioma. Herein, we describe the clinical, imaging, pathologic, and follow-up findings from 14 patients for a fourth component of the syndrome, adrenal adenoma. The adrenal neoplasm was asymptomatic and usually a late finding. Results of adrenocortical function tests were normal. Computed tomography revealed low-density adrenal masses that were consistent with adenomas. Bilateral lesions were present in 4 patients. In 13 of the 14 patients who underwent surgery, resected adrenal glands and biopsy specimens featured 1 or more circumscribed, yellow tumors, up to 3.5 cm in diameter, composed of well-differentiated polygonal cells with clear vacuolated cytoplasm and a smaller component of eosinophilic cells. The extratumoral cortex had combinations of normal histologic features, discrete clear cell micronodules, zonal clear cell hypertrophy, and marked atrophy. The lesion in the 14th patient was different, grossly and microscopically resembling the usual sporadic cortisol-secreting adenoma. After the tumor was excised, the patient required glucocorticoid support. None of the tumors recurred or metastasized. Fourteen additional patients had unilateral or bilateral adrenal tumors consistent with adenomas detected by imaging studies.
C1 [Carney, J. Aidan] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA.
[Young, William F., Jr.] Mayo Clin, Div Endocrinol Diabet Metab & Nutr, Rochester, MN 55905 USA.
[Stratakis, Constantine A.] NICHD, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA.
RP Carney, JA (reprint author), Mayo Clin, Dept Lab Med & Pathol, 200 First St SW, Rochester, MN 55905 USA.
EM carney.aidan@mayo.edu
FU NICHD, NIH [HD008920-01]
FX C.A.S. was supported by Intramural Program, NICHD, NIH, project:
HD008920-01. The authors have disclosed that they have no significant
relationships with, or financial interest in, any commercial companies
pertaining to this article.
NR 24
TC 10
Z9 10
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0147-5185
EI 1532-0979
J9 AM J SURG PATHOL
JI Am. J. Surg. Pathol.
PD AUG
PY 2013
VL 37
IS 8
BP 1140
EP 1149
PG 10
WC Pathology; Surgery
SC Pathology; Surgery
GA 299XH
UT WOS:000330428500003
PM 23681078
ER
PT J
AU Taieb, D
Urena-Torres, P
Zanotti-Fregonara, P
Rubello, D
Ferretti, A
Henter, I
Henry, JF
Schiavi, F
Opocher, G
Blickman, JG
Colletti, PM
Hindie, E
AF Taieb, David
Urena-Torres, Pablo
Zanotti-Fregonara, Paolo
Rubello, Domenico
Ferretti, Alice
Henter, Ioline
Henry, Jean-Francois
Schiavi, Francesca
Opocher, Giuseppe
Blickman, Johan G.
Colletti, Patrick M.
Hindie, Elif
TI Parathyroid Scintigraphy in Renal Hyperparathyroidism The Added
Diagnostic Value of SPECT and SPECT/CT
SO CLINICAL NUCLEAR MEDICINE
LA English
DT Review
DE parathyroid scintigraphy; Tc-99m-MIBI; dual isotope; hemodialysis;
secondary hyperparathyroidism; tertiary hyperparathyroidism; surgery
ID NEAR-TOTAL PARATHYROIDECTOMY; CHRONIC KIDNEY-DISEASE; LONG-TERM
SURVIVAL; SECONDARY HYPERPARATHYROIDISM; DIALYSIS PATIENTS;
TC-99M-SESTAMIBI SCINTIGRAPHY; TERTIARY HYPERPARATHYROIDISM;
CHRONIC-HEMODIALYSIS; MORTALITY RISK; SERUM-CALCIUM
AB Secondary hyperparathyroidism (sHPT) is a major complication for patients with end-stage renal disease on long-term hemodialysis or peritoneal dialysis. When the disease is resistant to medical treatment, patients with severe sHPT are typically referred for parathyroidectomy (PTx), which usually improves biological parameters as well as clinical signs and symptoms. Unfortunately, early surgical failure with persistent disease may occur in 5%-10% of patients and recurrence reaches 20%-30% at 5 years. Presently, the use of parathyroid scintigraphy in sHPT is usually limited to the management of surgical failures after initial PTx. This review describes the strengths and limitations of typical Tc-99m-sestamibi imaging protocols, and highlights the potential benefits of using parathyroid scintigraphy in the initial workup of surgical patients.
C1 [Taieb, David] Aix Marseille Univ, CERIMED, La Timone Univ Hosp, Dept Nucl Med, Marseille, France.
[Urena-Torres, Pablo] Clin Landy, St Ouen, France.
[Zanotti-Fregonara, Paolo; Henter, Ioline] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
[Rubello, Domenico; Ferretti, Alice] Santa Maria Misericordia Hosp, Dept Nucl Med, PET CT Ctr, I-45100 Rovigo, Italy.
[Henry, Jean-Francois] Aix Marseille Univ, La Timone Univ Hosp, Dept Endocrine Surg, Marseille, France.
[Schiavi, Francesca; Opocher, Giuseppe] IRCCS, Veneto Inst Oncol, Familial Canc Clin, Padua, Italy.
[Schiavi, Francesca; Opocher, Giuseppe] IRCCS, Veneto Inst Oncol, Padua, Italy.
[Opocher, Giuseppe] Univ Padua, Dept Med DIMED, Padua, Italy.
[Blickman, Johan G.] Golisano Childrens Hosp, Dept Imaging Sci URMC, Rochester, NY USA.
[Colletti, Patrick M.] Univ So Calif, Dept Radiol, Los Angeles, CA USA.
[Hindie, Elif] Univ Bordeaux, Haut Leveque Hosp, Dept Nucl Med, Bordeaux, France.
RP Rubello, D (reprint author), Santa Maria Misericordia Hosp, Dept Imaging, Via Tre Martiri 140, I-45100 Rovigo, Italy.
EM domenico.rubello@libero.it
RI Opocher, Giuseppe/F-3950-2014;
OI Opocher, Giuseppe/0000-0002-9845-9623; schiavi,
francesca/0000-0001-8529-4455
FU Intramural Research Program of the National Institute of Mental Health,
National Institutes of Health (IRP-NIMH-NIH)
FX The authors gratefully acknowledge the support of the Intramural
Research Program of the National Institute of Mental Health, National
Institutes of Health (IRP-NIMH-NIH).
NR 41
TC 9
Z9 9
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0363-9762
EI 1536-0229
J9 CLIN NUCL MED
JI Clin. Nucl. Med.
PD AUG
PY 2013
VL 38
IS 8
BP 630
EP 635
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 298WQ
UT WOS:000330355600016
PM 23751837
ER
PT J
AU Madan, RA
Arlen, PM
AF Madan, Ravi A.
Arlen, Philip M.
TI Recent advances revolutionize treatment of metastatic prostate cancer
SO FUTURE ONCOLOGY
LA English
DT Review
DE castration resistant; hormone therapy; immunotherapy; metastatic
prostate cancer
ID PHASE-III TRIAL; RE INTERDISCIPLINARY CRITIQUE; RANDOMIZED
CONTROLLED-TRIAL; DOCETAXEL PLUS PREDNISONE; PAINFUL BONE METASTASES;
SIPULEUCEL-T; DOUBLE-BLIND; ABIRATERONE ACETATE; OPEN-LABEL;
ANTIANDROGEN WITHDRAWAL
AB In 2004, the chemotherapy agent docetaxel was approved for the treatment of metastatic prostate cancer. Although it has taken almost a decade, significant new advances have been made in this area, including the clinical development of modern hormonal therapies, such as abiraterone and enzalutamide, and immunotherapies, such as sipuleucel-T, all of which have improved survival in metastatic prostate cancer. These agents have not only provided new therapeutic options for patients with advanced disease, they have also spurred research in both androgen receptor-targeting therapy and immunotherapy. Future trials will focus on the optimal sequence of these and other emerging therapies, with the aim of using these treatments earlier in the disease course (including the adjuvant setting) to enhance clinical benefit and potentially increase the cure rate for prostate cancer.
C1 [Madan, Ravi A.; Arlen, Philip M.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Arlen, PM (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM arlenp@mail.nih.gov
NR 83
TC 8
Z9 8
U1 0
U2 4
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1479-6694
EI 1744-8301
J9 FUTURE ONCOL
JI Future Oncol.
PD AUG
PY 2013
VL 9
IS 8
BP 1133
EP 1144
DI 10.2217/FON.13.65
PG 12
WC Oncology
SC Oncology
GA 292XP
UT WOS:000329936300015
PM 23902245
ER
PT J
AU Kerr, GD
Egbert, SD
Al-Nabulsi, I
Beck, HL
Cullings, HM
Endo, S
Hoshi, M
Imanaka, T
Kaul, DC
Maruyama, S
Reeves, GI
Ruehm, W
Sakaguchi, A
Simon, SL
Spriggs, GD
Stram, DO
Tonda, T
Weiss, JF
Weitz, RL
Young, RW
AF Kerr, George D.
Egbert, Stephen D.
Al-Nabulsi, Isaf
Beck, Harold L.
Cullings, Harry M.
Endo, Satoru
Hoshi, Masaharu
Imanaka, Tetsuji
Kaul, Dean C.
Maruyama, Satoshi
Reeves, Glen I.
Ruehm, Werner
Sakaguchi, Aya
Simon, Steven L.
Spriggs, Gregory D.
Stram, Daniel O.
Tonda, Tetsuji
Weiss, Joseph F.
Weitz, Ronald L.
Young, Robert W.
TI WORKSHOP REPORT ON ATOMIC BOMB DOSIMETRY-RESIDUAL RADIATION EXPOSURE:
RECENT RESEARCH AND SUGGESTIONS FOR FUTURE STUDIES
SO HEALTH PHYSICS
LA English
DT Article
DE atomic bomb; atomic bomb survivors; fallout; radiation effects
ID FALLOUT DEPOSITION; BLACK RAIN; HIROSHIMA; U-235/U-238; SURVIVORS;
NAGASAKI; RATIOS
AB There is a need for accurate dosimetry for studies of health effects in the Japanese atomic bomb survivors because of the important role that these studies play in worldwide radiation protection standards. International experts have developed dosimetry systems, such as the Dosimetry System 2002 (DS02), which assess the initial radiation exposure to gamma rays and neutrons but only briefly consider the possibility of some minimal contribution to the total body dose by residual radiation exposure. In recognition of the need for an up-to-date review of the topic of residual radiation exposure in Hiroshima and Nagasaki, recently reported studies were reviewed at a technical session at the 57th Annual Meeting of the Health Physics Society in Sacramento, California, 22-26 July 2012. A one-day workshop was also held to provide time for detailed discussion of these newer studies and to evaluate their potential use in clarifying the residual radiation exposures to the atomic-bomb survivors at Hiroshima and Nagasaki. Suggestions for possible future studies are also included in this workshop report.
C1 [Kerr, George D.] Kerr Consulting, Knoxville, TN USA.
[Kerr, George D.] Oak Ridge Associated Univ, Oak Ridge, TN 37831 USA.
[Egbert, Stephen D.] Sci Applicat Int Corp, San Diego, CA 92121 USA.
[Al-Nabulsi, Isaf; Weiss, Joseph F.] US DOE, Washington, DC 20585 USA.
[Beck, Harold L.] US DOE, New York, NY USA.
[Cullings, Harry M.] Radiat Effects Res Fdn, Hiroshima, Japan.
[Endo, Satoru] Prefectural Univ Hiroshima, Hiroshima, Japan.
[Hoshi, Masaharu; Sakaguchi, Aya; Tonda, Tetsuji] Hiroshima Univ, Hiroshima 730, Japan.
[Imanaka, Tetsuji] Kyoto Univ, Kyoto 6068501, Japan.
[Kaul, Dean C.] SAIC, Park City, UT USA.
[Maruyama, Satoshi] Minist Hlth Labour & Welf, Tokyo, Japan.
[Reeves, Glen I.] Appl Res Associates, Arlington, VA USA.
[Ruehm, Werner] Helmholtz Zentrum Muenchen, German Res Ctr Environm Hlth, Neuherberg, Germany.
[Simon, Steven L.] NCI, NIH, Bethesda, MD 20892 USA.
[Spriggs, Gregory D.] Lawrence Livermore Natl Lab, Livermore, CA USA.
[Stram, Daniel O.] Univ So Calif, Los Angeles, CA USA.
[Weitz, Ronald L.] SAIC, Albuquerque, NM USA.
[Young, Robert W.] Def Nucl Agcy, Winter Pk, FL USA.
RP Kerr, GD (reprint author), Oak Ridge Associated Univ, POB 117, Oak Ridge, TN 37831 USA.
EM George.Kerr@orau.org
RI Sakaguchi, Aya/E-8134-2015; Endo, Satoru/D-9091-2012;
OI Endo, Satoru/0000-0001-5961-681X; Hoshi, Masaharu/0000-0001-6978-0883
FU U.S. Department of Energy (DOE)
FX We wish to thank David Landguth, Oak Ridge National Laboratory, for his
organizational expertise that resulted in a highly successful workshop.
The help and advice of the Health Physics Society meeting organizers and
the staff of Burk and Associates are greatly appreciated. We would also
like to thank John Boice for his excellent presentation at the start of
the technical session, although he was not able to participate in the
workshop. The participation of George D. Kerr, Steve D. Egbert, Harold
L. Beck, Harry M. Cullings, Satoru Endo, Masaharu Hoshi, Tetsuji
Imanaka, Dean C. Kaul, Aya Sakaguchi, Gregory D. Springs, Daniel O.
Stram, and R. L. Weitz in the workshop was financially supported by the
U.S. Department of Energy (DOE). The views of the authors do not
necessarily reflect those of the DOE, the U.S. government, or the
authors' institutions.
NR 24
TC 8
Z9 8
U1 0
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0017-9078
EI 1538-5159
J9 HEALTH PHYS
JI Health Phys.
PD AUG
PY 2013
VL 105
IS 2
BP 140
EP 149
DI 10.1097/HP.0b013e31828ca73a
PG 10
WC Environmental Sciences; Public, Environmental & Occupational Health;
Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical
Imaging
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Nuclear Science & Technology; Radiology, Nuclear Medicine &
Medical Imaging
GA 299AT
UT WOS:000330367400004
PM 23799498
ER
PT J
AU Gennuso, KP
Gangnon, RE
Matthews, CE
Thraen-Borowski, KM
Colbert, LH
AF Gennuso, Keith P.
Gangnon, Ronald E.
Matthews, Charles E.
Thraen-Borowski, Keith M.
Colbert, Lisa H.
TI Sedentary Behavior, Physical Activity, and Markers of Health in Older
Adults
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Article
DE NHANES; AGING; PHYSICAL FUNCTION; SITTING; CARDIOMETABOLIC RISK
ID BREAST-CANCER RISK; METABOLIC SYNDROME; UNITED-STATES; SITTING TIME;
ASSOCIATIONS; ACCELEROMETER; WOMEN; CALIBRATION; BIOMARKERS; OBESITY
AB Introduction: The purpose of this study was to examine the association between sedentary behavior (SB), cardiometabolic risk factors, and self-reported physical function by level of moderate-vigorous physical activity (MVPA). Methods: Cross-sectional analysis was completed on 1914 older adults age >= 65 yr from the 2003-2006 U. S. National Health and Nutrition Examination Survey. MVPA and SB were derived from ActiGraph accelerometers worn for 1 wk. MVPA was categorized as sufficient to meet the current U. S. guidelines (>= 150 min.wk(-1)) or not; SB was split into quartiles. Various biomarkers were examined in laboratory analyses and physical exams, and the number of functional limitations was self-reported. Statistical interaction between SB and MVPA on the biomarker associations was the primary analysis, followed by an examination of their independent associations with relevant covariate adjustment. Results: Average SB was 9.4 +/- 2.3 h.d(-1) (mean +/- SD), and approximately 35% were classified as sufficiently active. Overall, no significant meaningful statistical interactions were found between SB and MVPA for any of the outcomes; however, strong independent positive associations were found between SB and weight (P < 0.01), body mass index (P < 0.01), waist circumference (P < 0.01), C-reactive protein (P < 0.01), plasma glucose (P = 0.04), and number of functional limitations (P < 0.01) after adjustment for MVPA. Similarly, MVPA was negatively associated with weight (P = 0.01), body mass index (P < 0.01), waist circumference (P < 0.01), diastolic blood pressure (P = 0.04), C-reactive protein (P G 0.01), and number of functional limitations (P < 0.01) after adjustment for SB. Conclusions: The results suggest that sufficient MVPA did not ameliorate the negative associations between SB and cardiometabolic risk factors or functional limitations in the current sample and that there was independence on a multiplicative scale in their associations with the outcomes examined. Thus, older adults may benefit from the joint prescription to accumulate adequate MVPA and avoid prolonged sitting.
C1 [Gennuso, Keith P.; Thraen-Borowski, Keith M.; Colbert, Lisa H.] Univ Wisconsin, Dept Kinesiol, Madison, WI 53706 USA.
[Gangnon, Ronald E.] Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI 53706 USA.
[Gangnon, Ronald E.] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53706 USA.
[Matthews, Charles E.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Colbert, LH (reprint author), Univ Wisconsin, Dept Kinesiol, 2035 Gymnasium Natatorium,2000 Observ DR, Madison, WI 53706 USA.
EM lhcolbert@education.wisc.edu
RI matthews, Charles/E-8073-2015
OI matthews, Charles/0000-0001-8037-3103
NR 25
TC 69
Z9 72
U1 3
U2 26
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
EI 1530-0315
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD AUG
PY 2013
VL 45
IS 8
BP 1493
EP 1500
DI 10.1249/MSS.0b013e318288a1e5
PG 8
WC Sport Sciences
SC Sport Sciences
GA 300KT
UT WOS:000330463500009
PM 23475142
ER
PT J
AU Melanson, EL
Keadle, SK
Donnelly, JE
Braun, B
King, NA
AF Melanson, Edward L.
Keadle, Sarah Kozey
Donnelly, Joseph E.
Braun, Barry
King, Neil A.
TI Resistance to Exercise-Induced Weight Loss: Compensatory Behavioral
Adaptations
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Article
DE ENERGY EXPENDITURE; PHYSICAL ACTIVITY; NONEXERCISE ACTIVITY
THERMOGENESIS; ENERGY INTAKE
ID SPONTANEOUS PHYSICAL-ACTIVITY; RANDOMIZED CONTROLLED-TRIAL; DAILY
ENERGY-EXPENDITURE; BODY-COMPOSITION; FOOD-INTAKE; LONG-TERM; ACTIVITY
THERMOGENESIS; SEDENTARY BEHAVIOR; AEROBIC CAPACITY; APPETITE CONTROL
AB In many interventions that are based on an exercise program intended to induce weight loss, the mean weight loss observed is modest and sometimes far less than what the individual expected. The individual responses are also widely variable, with some individuals losing a substantial amount of weight, others maintaining weight, and a few actually gaining weight. The media have focused on the subpopulation that loses little weight, contributing to a public perception that exercise has limited utility to cause weight loss. The purpose of the symposium was to present recent, novel data that help explain how compensatory behaviors contribute to a wide discrepancy in exercise-induced weight loss. The presentations provide evidence that some individuals adopt compensatory behaviors, that is, increased energy intake and/or reduced activity, that offset the exercise energy expenditure and limit weight loss. The challenge for both scientists and clinicians is to develop effective tools to identify which individuals are susceptible to such behaviors and to develop strategies to minimize their effect.
C1 [Melanson, Edward L.] Univ Colorado, Sch Med, Div Endocrinol Metab & Diabet, Denver, CO USA.
[Melanson, Edward L.] Univ Colorado, Sch Med, Div Geriatr Med, Denver, CO USA.
[Keadle, Sarah Kozey] NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA.
[Donnelly, Joseph E.] Univ Kansas, Ctr Phys Act & Weight Management, Lawrence, KS 66045 USA.
[Braun, Barry] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Dept Kinesiol, Amherst, MA 01003 USA.
[King, Neil A.] Queensland Univ Technol, Sch Exercise & Nutr Sci, Inst Hlth & Biomed Innovat, Brisbane, Qld 4001, Australia.
RP Melanson, EL (reprint author), Univ Colorado Aurora, Anschutz Med Campus,MS 8106,12801 East 17th Ave, Denver, CO 80045 USA.
EM Ed.melanson@ucdenver.edu
OI Keadle, Sarah/0000-0002-9569-9306
FU NIH [DK07708, UL1 RR025780, RC1HL099557, DK49191]
FX Work related to this symposium was supported by the following grants:
NIH DK07708 and UL1 RR025780 (Dr. Melanson), NIH RC1HL099557 (Dr. Kozey
Keadle and Dr. Barry Braun), and NIH DK49191 (Dr. Donnelly).
NR 76
TC 21
Z9 21
U1 1
U2 15
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
EI 1530-0315
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD AUG
PY 2013
VL 45
IS 8
BP 1600
EP 1609
DI 10.1249/MSS.0b013e31828ba942
PG 10
WC Sport Sciences
SC Sport Sciences
GA 300KT
UT WOS:000330463500022
PM 23470300
ER
PT J
AU Matthews, CE
Keadle, SK
Sampson, J
Lyden, K
Bowles, HR
Moore, SC
Libertine, A
Freedson, PS
Fowke, JH
AF Matthews, Charles E.
Keadle, Sarah Kozey
Sampson, Joshua
Lyden, Kate
Bowles, Heather R.
Moore, Stephen C.
Libertine, Amanda
Freedson, Patty S.
Fowke, Jay H.
TI Validation of a Previous-Day Recall Measure of Active and Sedentary
Behaviors
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Article
DE EXPOSURE ASSESSMENT; MEASUREMENT ERROR; PHYSICAL ACTIVITY; BEHAVIORAL
EPIDEMIOLOGY
ID PHYSICAL-ACTIVITY QUESTIONNAIRES; DAILY ENERGY-EXPENDITURE; SOCIAL
DESIRABILITY; ACTIVITY MONITOR; SELF-REPORT; MEASUREMENT ERROR;
COMPUTER-SCIENCE; UNITED-STATES; TIME SPENT; ADULTS
AB Purpose: A previous-day recall (PDR) may be a less error-prone alternative to traditional questionnaire-based estimates of physical activity and sedentary behavior (e.g., past year), but the validity of the method is not established. We evaluated the validity of an interviewer administered PDR in adolescents (12-17 yr) and adults (18-71 yr). Methods: In a 7-d study, participants completed three PDR, wore two activity monitors, and completed measures of social desirability and body mass index. PDR measures of active and sedentary time was contrasted against an accelerometer (ActiGraph) by comparing both to a valid reference measure (activPAL) using measurement error modeling and traditional validation approaches. Results: Age- and sex-specific mixed models comparing PDR to activPAL indicated the following: 1) there was a strong linear relationship between measures for sedentary (regression slope, beta(1) = 0.80-1.13) and active time (beta(1) = 0.64-1.09), 2) person-specific bias was lower than random error, and 3) correlations were high (sedentary: r = 0.60-0.81; active: r = 0.52-0.80). Reporting errors were not associated with body mass index or social desirability. Models comparing ActiGraph to activPAL indicated the following: 1) there was a weaker linear relationship between measures for sedentary (beta(1) = 0.63-0.73) and active time (beta(1) = 0.61-0.72), (2) person-specific bias was slightly larger than random error, and (3) correlations were high (sedentary: r = 0.68-0.77; active: r = 0.57-0.79). Conclusions: Correlations between the PDR and the activPAL were high, systematic reporting errors were low, and the validity of the PDR was comparable with the ActiGraph. PDR may have value in studies of physical activity and health, particularly those interested in measuring the specific type, location, and purpose of activity-related behaviors.
C1 [Matthews, Charles E.; Moore, Stephen C.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Keadle, Sarah Kozey; Lyden, Kate; Libertine, Amanda; Freedson, Patty S.] Univ Massachusetts, Dept Kinesiol, Amherst, MA 01003 USA.
[Sampson, Joshua] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Bowles, Heather R.] NCI, Risk Factor Monitoring & Methods Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Fowke, Jay H.] Vanderbilt Univ, Sch Med, Dept Med, Div Epidemiol, Nashville, TN 37212 USA.
RP Matthews, CE (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NCI Shady Grove, 9609 Med Ctr Dr,Room 6E340,MSC 9704, Bethesda, MD 20892 USA.
EM charles.matthews2@nih.gov
RI matthews, Charles/E-8073-2015; Moore, Steven/D-8760-2016;
OI matthews, Charles/0000-0001-8037-3103; Moore,
Steven/0000-0002-8169-1661; Keadle, Sarah/0000-0002-9569-9306
FU National Institutes of Health [R01NR011477]; Intramural Research Program
of the National Institutes of Health
FX This research was supported by funding from the National Institutes of
Health (grant no. R01NR011477) to Drs. Fowke and Freedson. The
Intramural Research Program of the National Institutes of Health
supported Dr. Matthews work on this project.
NR 50
TC 39
Z9 39
U1 2
U2 20
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
EI 1530-0315
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD AUG
PY 2013
VL 45
IS 8
BP 1629
EP 1638
DI 10.1249/MSS.0b013e3182897690
PG 10
WC Sport Sciences
SC Sport Sciences
GA 300KT
UT WOS:000330463500026
PM 23863547
ER
PT J
AU Mahnke, YD
Beddall, MH
Roederer, M
AF Mahnke, Yolanda D.
Beddall, Margaret H.
Roederer, Mario
TI OMIP-019: Quantification of Human gamma delta T-Cells, iNKT-Cells, and
Hematopoietic Precursors
SO CYTOMETRY PART A
LA English
DT Article
C1 [Mahnke, Yolanda D.; Beddall, Margaret H.; Roederer, Mario] NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Mahnke, YD (reprint author), Univ Penn, Translat & Correlat Studies Lab, Philadelphia, PA 19104 USA.
EM Yolanda.Mahnke@uphs.upenn.edu
NR 11
TC 4
Z9 4
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4922
EI 1552-4930
J9 CYTOM PART A
JI Cytom. Part A
PD AUG
PY 2013
VL 83A
IS 8
BP 676
EP 678
DI 10.1002/cyto.22326
PG 3
WC Biochemical Research Methods; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 297HH
UT WOS:000330246000002
PM 23897714
ER
PT J
AU Wintermark, M
Fiehler, J
Kudo, K
Liebeskind, DS
Luby, M
Michel, P
Nogueira, R
Parsons, M
Sasaki, M
Wardlaw, J
Wu, O
Zhang, WW
Zhu, GM
Warach, S
AF Wintermark, Max
Fiehler, Jens
Kudo, Kohsuke
Liebeskind, David S.
Luby, Marie
Michel, Patrik
Nogueira, Raul
Parsons, Mark
Sasaki, Makoto
Wardlaw, Joanna
Wu, Ona
Zhang, Weiwei
Zhu, Guangming
Warach, Steven
CA Stroke Imaging Res STIR
VISTA-Imaging Investigators
TI International Survey of Acute Stroke Imaging Capabilities We Need You!
SO STROKE
LA English
DT Editorial Material
DE acute stroke; computed tomography; imaging; magnetic resonance imaging;
perfusion imaging; thrombolysis
C1 [Wintermark, Max] Univ Virginia, Dept Radiol, Charlottesville, VA USA.
[Wintermark, Max] CHU Vaudois, Dept Radiol, Lausanne, Switzerland.
[Fiehler, Jens] Univ Med Ctr Hamburg Eppendorf, Hamburg, Germany.
[Kudo, Kohsuke] Hokkaido Univ Hosp, Dept Diagnost Radiol, Sapporo, Hokkaido 060, Japan.
[Liebeskind, David S.] UCLA Stroke Ctr, Los Angeles, CA USA.
[Luby, Marie] NINDS, NIH, Bethesda, MD 20892 USA.
[Michel, Patrik] CHU Vaudois, Lausanne, Switzerland.
[Michel, Patrik] Univ Lausanne, Lausanne, Switzerland.
[Nogueira, Raul] Emory Univ, Sch Med, Grady Mem Hosp, Marcus Stroke & Neurosci Ctr, Atlanta, GA USA.
[Parsons, Mark] Univ Newcastle, John Hunter Hosp, Hunter Med Res Inst, Dept Neurol, Callaghan, NSW 2308, Australia.
[Sasaki, Makoto] Iwate Med Univ, Inst Biomed Sci, Yahaba, Iwate, Japan.
[Wardlaw, Joanna] Univ Edinburgh, Div Neuroimaging Sci, Ctr Clin Brain Sci, Brain Res Imaging Ctr, Edinburgh, Midlothian, Scotland.
[Wu, Ona] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Wu, Ona] Harvard Univ, Sch Med, Boston, MA USA.
[Warach, Steven] UT Southwestern Med Ctr, Seton UT Southwestern Clin Res Inst Austin, Dept Neurol & Neurotherapeut, Austin, TX USA.
[Zhang, Weiwei; Zhu, Guangming] Mil Gen Hosp Beijing PLA, Dept Neurol, Beijing, Peoples R China.
RP Wintermark, M (reprint author), UVA Dept Radiol, Neuroradiol Div, Box 800170, Charlottesville, VA 22908 USA.
EM Max.Wintermark@gmail.com
RI Parsons, Mark/G-3750-2014; Michel, Patrik/Q-2275-2016;
OI Michel, Patrik/0000-0003-4954-7579; Wintermark, Max/0000-0002-6726-3951
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
EI 1524-4628
J9 STROKE
JI Stroke
PD AUG
PY 2013
VL 44
IS 8
BP 2091
EP 2091
DI 10.1161/STROKEAHA.113.001441
PG 1
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 293OO
UT WOS:000329982400015
ER
PT J
AU Garrison, KA
Aziz-Zadeh, L
Wong, SW
Liew, SL
Winstein, CJ
AF Garrison, Kathleen Alice
Aziz-Zadeh, Lisa
Wong, Savio Waiho
Liew, Sook-Lei
Winstein, Carolee Joyce
TI Modulating the Motor System by Action Observation After Stroke
SO STROKE
LA English
DT Article
DE action observation; mirror neuron system; plasticity; rehabilitation;
stroke
ID MIRROR-NEURON SYSTEM; HAND ACTIONS; REHABILITATION; IMITATION; FMRI;
RECOVERY; THERAPY; DANCERS; BRAIN
AB Background and Purpose Much recent interest surrounds the use of action observation, which is observing another individual performing a motor task, in stroke rehabilitation, to promote motor recovery by engaging similar brain regions to action execution. This may be especially useful in individuals with limited mobility. Here, we assess how cortical motor activity during action observation is affected by stroke and by stroke-related motor deficits.
Methods We used functional MRI to compare brain activity during right and left hand action observation in right-handed nondisabled participants and participants who were right-handed before left hemisphere stroke. All participants performed the same actions after their functional MRI.
Results Nondisabled participants show greater bilateral cortical motor activity when observing actions made using the left hand, whereas participants with stroke show greater ipsilesional cortical motor activity when observing actions made using the right (paretic) hand (P<0.05; corrected). For both groups, action processing is modulated by motor capability: cortical motor activity is greater when observing the hand with lower motor scores (P<0.05; corrected). Furthermore, for stroke, the extent of ipsilesional activity correlates with lesion volume (P=0.049), in a pattern that suggests adaptive plasticity.
Conclusions We found that action observation activates specific motor plans in damaged motor circuits after stroke, and this activity is related to motor capability to perform the same actions. Cortical motor activity during action observation may be relevant to motor learning, and to motor relearning in stroke rehabilitation.
C1 [Garrison, Kathleen Alice; Winstein, Carolee Joyce] Univ So Calif, Div Biokinesiol & Phys Therapy, Los Angeles, CA USA.
[Garrison, Kathleen Alice; Aziz-Zadeh, Lisa; Wong, Savio Waiho; Liew, Sook-Lei] Univ So Calif, Brain & Creat Inst, Los Angeles, CA USA.
[Aziz-Zadeh, Lisa; Liew, Sook-Lei] Univ So Calif, Div Occupat Sci & Occupat Therapy, Los Angeles, CA USA.
[Garrison, Kathleen Alice] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA.
[Wong, Savio Waiho] Hong Kong Inst Educ, Dept Special Educ & Counseling, Hong Kong, Hong Kong, Peoples R China.
[Liew, Sook-Lei] NINDS, Human Cort Physiol & Stroke Neurorehabil Sect, Bethesda, MD 20892 USA.
RP Garrison, KA (reprint author), Yale Univ, 950 Campbell Ave,Bldg 36, West Haven, CT 06516 USA.
EM kathleenalice@gmail.com
OI Wong, Savio/0000-0003-2854-5830
FU American Heart Association [10SDG3510062]; National Institutes of
Health, Eunice Kennedy Shriver National Institute of Child Health and
Human Development [R03HD067475]; National Institute of Biomedical
Imaging and Bioengineering [EB00438]
FX This work was supported by American Heart Association (10SDG3510062);
National Institutes of Health, Eunice Kennedy Shriver National Institute
of Child Health and Human Development (R03HD067475); and the National
Institute of Biomedical Imaging and Bioengineering (EB00438). The
content of this study is the responsibility of the authors and does not
reflect the views of the funding bodies.
NR 29
TC 16
Z9 17
U1 1
U2 22
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
EI 1524-4628
J9 STROKE
JI Stroke
PD AUG
PY 2013
VL 44
IS 8
BP 2247
EP 2253
DI 10.1161/STROKEAHA.113.001105
PG 7
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 293OO
UT WOS:000329982400040
PM 23743974
ER
PT J
AU Vickrey, BG
Brott, TG
Koroshetz, WJ
AF Vickrey, Barbara G.
Brott, Thomas G.
Koroshetz, Walter J.
CA Stroke Res Priorities Meeting Stee
Natl Advisory Neurological Disorde
Natl Inst Neurological Disorders S
TI Research Priority Setting A Summary of the 2012 NINDS Stroke Planning
Meeting Report
SO STROKE
LA English
DT Article
DE cerebrovascular diseases; health priorities; planning; recommendations;
research design; research priorities
ID UNITED-STATES; DISEASE
C1 [Vickrey, Barbara G.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA.
[Brott, Thomas G.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA.
[Koroshetz, Walter J.] NINDS, Bethesda, MD 20892 USA.
RP Koroshetz, WJ (reprint author), NINDS, NIH, Bldg 31,Room 8A52,31 Ctr Dr MSC 2540, Bethesda, MD 20892 USA.
EM koroshetzw@mail.nih.gov
NR 6
TC 12
Z9 12
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
EI 1524-4628
J9 STROKE
JI Stroke
PD AUG
PY 2013
VL 44
IS 8
BP 2338
EP 2342
DI 10.1161/STROKEAHA.113.001196
PG 5
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 293OO
UT WOS:000329982400057
PM 23821224
ER
PT J
AU Moskowitz, MA
Grotta, JC
Koroshetz, WJ
AF Moskowitz, Michael A.
Grotta, James C.
Koroshetz, Walter J.
CA Stroke Progress Review Grp
Natl Inst Neurological Disorders S
TI The NINDS Stroke Progress Review Group Final Analysis and
Recommendations
SO STROKE
LA English
DT Article
DE planning; priorities; recommendations
C1 [Moskowitz, Michael A.] Massachusetts Gen Hosp, Ctr Neurosci, Boston, MA 02129 USA.
[Grotta, James C.] Univ Texas Med Sch Houston, Dept Neurol, Houston, TX USA.
[Koroshetz, Walter J.] NINDS, NIH, Bethesda, MD 20892 USA.
RP Koroshetz, WJ (reprint author), NINDS, NIH, Bldg 31,Room 8A52,Ctr Dr MSC 2540, Bethesda, MD 20892 USA.
EM koroshetzw@mail.nih.gov
FU Haemonetics
FX Dr Grotta receives grant support from Haemonetics and is a consultant
for Lundbeck. The other authors have no conflicts to report.
NR 1
TC 6
Z9 7
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
EI 1524-4628
J9 STROKE
JI Stroke
PD AUG
PY 2013
VL 44
IS 8
BP 2343
EP 2350
DI 10.1161/STROKEAHA.113.001192
PG 8
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 293OO
UT WOS:000329982400058
PM 23821230
ER
PT J
AU Raynor, LA
Schreiner, PJ
Loria, CM
Carr, JJ
Pletcher, MJ
Shikany, JM
AF Raynor, Lewis A.
Schreiner, Pamela J.
Loria, Catherine M.
Carr, J. Jeffrey
Pletcher, Mark J.
Shikany, James M.
TI Associations of retrospective and concurrent lipid levels with
subclinical atherosclerosis prediction after 20 years of follow-up: the
Coronary Artery Risk Development in Young Adults (CARDIA) study
SO ANNALS OF EPIDEMIOLOGY
LA English
DT Article
DE Atherosclerosis; Lipids; Risk
ID SCHOOL-AGE CHILDREN; CARDIOVASCULAR RISK; HEART-DISEASE; CHILDHOOD;
CHOLESTEROL; MUSCATINE; CALCIFICATION; ADOLESCENTS; GUIDELINES;
THICKNESS
AB Purpose: Using data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, we sought to determine how well lipids measured at baseline and at 20 years predict the presence of subclinical atherosclerosis.
Methods: Complete risk factor, coronary artery calcification (CAC), and carotid intima media thickness (CIMT) data were available for 2435 participants. Lipids were categorized into quartiles, CAC at Y20 was dichotomized as present/absent, and CIMT was dichotomized as >= 84 or <84th overall percentile. Multivariable logistic regression was used to model the association between lipids and CAC/CIMT. C statistics were used to assess the discriminative value of each lipid measure in predicting the presence of CAC or CIMT at Y20.
Results: Lipid levels measured in young adulthood as well as middle age were both associated with subclinical disease in middle age. The discriminatory value of lipids was virtually identical at baseline, when participants were 18-30 years of age, and 20 years later. Neither baseline nor Y20 lipid data were strong predictors of Y20 subclinical disease despite statistically significant associations.
Conclusions: These results are consistent with a growing body of evidence that early-life exposure to nonoptimal lipids matters and lifestyle modifications administered earlier in the lifespan could slow the progress of the atherosclerotic plaques. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Raynor, Lewis A.] Univ Minnesota, Dept Pediat, Div Acad Gen Pediat, Minneapolis, MN 55414 USA.
[Schreiner, Pamela J.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN 55414 USA.
[Loria, Catherine M.] NHLBI, Bethesda, MD 20892 USA.
[Carr, J. Jeffrey] Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27103 USA.
[Pletcher, Mark J.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Pletcher, Mark J.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Shikany, James M.] Univ Alabama Birmingham, Sch Med, Div Prevent Med, Birmingham, AL USA.
RP Raynor, LA (reprint author), Univ Minnesota, Dept Pediat, Div Acad Gen Pediat, 717 Delaware St SE Suite 353,3rd Floor West, Minneapolis, MN 55414 USA.
EM rayno007@umn.edu
RI Carr, John/A-1938-2012
OI Carr, John/0000-0002-4398-8237
FU National Heart. Lung, and Blood Institute [N01-HC-48047, N01-HC-48048,
N01-HC-48049, N01-HC-48050, N01-HC-95095, HHSN268200425204 C,
HHSN26820042505 C]
FX The Coronary Artery Risk Development in Young Adults (CARDIA) Study is
supported by the following National Heart. Lung, and Blood Institute
contracts: N01-HC-48047, N01-HC-48048, N01-HC-48049, and N01-HC-48050
(clinics); N01-HC-95095 (coordinating center); and HHSN268200425204 C
and HHSN26820042505 C (imaging reading centers).
NR 24
TC 3
Z9 3
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1047-2797
EI 1873-2585
J9 ANN EPIDEMIOL
JI Ann. Epidemiol.
PD AUG
PY 2013
VL 23
IS 8
BP 492
EP 497
DI 10.1016/j.annepidem.2013.06.003
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 294AR
UT WOS:000330015300006
PM 23889858
ER
PT J
AU Wainer, IW
AF Wainer, Irving W.
TI Interview with Irving W Wainer
SO BIOANALYSIS
LA English
DT Editorial Material
AB Irving W Wainer, Senior Investigator in the Intramural Research Program at the National Institute on Aging/NIH received his PhD degree in chemistry from Cornell University and did postdoctoral doctoral studies in molecular biology (University of Oregon) and clinical pharmacology (Thomas Jefferson Medical School). He worked for the US FDA and held positions at St Jude's Children's Research Hospital, at McGill University as Professor in the Department of Oncology, and as a Professor of Pharmacology at Georgetown University. Wainer has published over 350 scientific papers, 10 books, 25 book chapters and holds 11 patents. His awards include: A.J.P. Martin Medal' presented by the Chromatographic Society; Doctor HonorisCausa awarded by the Medical University of Gdansk (Gdansk, Poland, 2006), Doctor HonorisCausa awarded by the Department of Medicine, University of Liege (Liege, Belgium, 2012), and the 2013 Eastern Analytical Symposium Award for Outstanding Contributions to the Fields of Analytical Chemistry. Wainer's research includes the development of new therapeutic agents for the treatment of congestive heart failure, cancer, pain and depression, many of which are in the later stages of drug development. His laboratory has also continued the development of cellular membrane affinity chromatography technology, and recent work includes the development of columns containing immobilized forms of the breast cancer resistance protein found in cellular and nuclear membranes and mitochondrial membrane columns. Wainer's laboratory has also continued its study of the effect of disease progression and aging on drug metabolism in critically ill and terminal patients. Interview was conducted by Lisa Parks, Assistant Commissioning Editor of Bioanalysis.
C1 NIA, Bioanalyt Chem & Drug Discovery Sect, Lab Clin Investigat, NIH, Baltimore, MD 21224 USA.
RP Wainer, IW (reprint author), NIA, Bioanalyt Chem & Drug Discovery Sect, Lab Clin Investigat, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM wainerir@grc.nia.nih.gov
NR 0
TC 0
Z9 0
U1 1
U2 8
PU FUTURE SCI LTD
PI LONDON
PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND
SN 1757-6180
EI 1757-6199
J9 BIOANALYSIS
JI Bioanalysis
PD AUG
PY 2013
VL 5
IS 16
BP 1949
EP 1952
DI 10.4155/BIO.13.135
PG 4
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 288PL
UT WOS:000329623800007
PM 23937128
ER
PT J
AU Hong, WMC
Amara, SG
AF Hong, Weimin C.
Amara, Susan G.
TI Differential targeting of the dopamine transporter to recycling or
degradative pathways during amphetamine- or PKC-regulated endocytosis in
dopamine neurons
SO FASEB JOURNAL
LA English
DT Article
DE ubiquitination; internalization; endosome sorting; fluorescence imaging
ID RECEPTOR TRAFFICKING; SURFACE EXPRESSION; XENOPUS OOCYTES; CELL-LINES;
MEMBRANE; INTERNALIZATION; MICROSCOPY; MECHANISM; BINDING;
METHAMPHETAMINE
AB The dopamine transporter (DAT) clears the extracellular dopamine released during neurotransmission and is a major target for both therapeutic and addictive psychostimulant amphetamines. Amphetamine exposure or activation of protein kinase C (PKC) by the phorbol ester PMA has been shown to down-regulate cell surface DAT. However, in dopamine neurons, the trafficking itinerary and fate of internalized DAT has not been elucidated. By monitoring surface-labeled DAT in transfected dopamine neurons from embryonic rat mesencephalic cultures, we find distinct sorting and fates of internalized DAT after amphetamine or PMA treatment. Although both drugs promote DAT internalization above constitutive endocytosis in dopamine neurons, PMA induces ubiquitination of DAT and leads to accumulation of DAT on LAMP1-positive endosomes. In contrast, after amphetamine exposure DAT is sorted to recycling endosomes positive for Rab11 and the transferrin receptor. Furthermore, quantitative assessment of DAT recycling using an antibody-feeding assay reveals that significantly less DAT returns to the surface of dopamine neurons after internalization by PMA, compared with vehicle or amphetamine treatment. These results demonstrate that, in neurons, the DAT is sorted differentially to recycling and degradative pathways after psychostimulant exposure or PKC activation, which may allow for either the transient or sustained inhibition of DAT during dopamine neurotransmission.
C1 [Hong, Weimin C.; Amara, Susan G.] Univ Pittsburgh, Dept Neurobiol, Pittsburgh, PA USA.
RP Amara, SG (reprint author), NIMH, Ctr Dr, 10 Ctr Dr,Room 4N222, Bethesda, MD 20814 USA.
EM susan.amara@nih.gov
FU American Recovery and Reinvestment Act funds; U.S. National Institutes
of Health [DA07595]
FX The authors thank Yong-Jian Liu, Alexander Sorkin, Willi Halfter, Geoff
Murdoch, Mee Choi, Linton Traub, Ora Weisz, Gerald Apodaca, and Katy
Baty (University of Pittsburgh, Pittsburgh, PA, USA) for valuable
suggestions or various DNA constructs and antibodies. The authors also
appreciate critiques from Spencer Watts, Mads Larsen, Ethan Block, Jie
Jiang, and other members of the S.G.A. laboratory. This work was
supported by American Recovery and Reinvestment Act funds and a U.S.
National Institutes of Health grant (DA07595) to S.G.A.
NR 45
TC 10
Z9 11
U1 0
U2 3
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
EI 1530-6860
J9 FASEB J
JI Faseb J.
PD AUG
PY 2013
VL 27
IS 8
BP 2995
EP 3007
DI 10.1096/fj.12-218727
PG 13
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 292BT
UT WOS:000329877600008
PM 23612789
ER
PT J
AU Ackermann, MA
Patel, PD
Valenti, J
Takagi, Y
Homsher, E
Sellers, JR
Kontrogianni-Konstantopoulos, A
AF Ackermann, Maegen A.
Patel, Puja D.
Valenti, Jane
Takagi, Yasuharu
Homsher, Earl
Sellers, James R.
Kontrogianni-Konstantopoulos, Aikaterini
TI Loss of actomyosin regulation in distal arthrogryposis myopathy due to
mutant myosin binding protein-C slow
SO FASEB JOURNAL
LA English
DT Article
DE actin; contractility; MYBPC1; skeletal muscle
ID RABBIT SKELETAL-MUSCLE; MYBP-C; CARDIAC MYOSIN; THICK FILAMENT; F-ACTIN;
DOMAIN; MUTATIONS; ISOFORM; SITE; CONTRACTION
AB Myosin binding protein C (MyBP-C) is expressed in striated muscles, where it plays key roles in the modulation of actomyosin cross-bridges. Slow MyBP-C (sMyBP-C) consists of multiple variants sharing common domains but also containing unique segments within the NH2 and COOH termini. Two missense mutations in the NH2 terminus (W236R) and COOH terminus (Y856H) of sMyBP-C have been causally linked to the development of distal arthrogryposis-1 (DA-1), a severe skeletal muscle disorder. Using a combination of in vitro binding and motility assays, we show that the COOH terminus mediates binding of sMyBP-C to thick filaments, while the NH2 terminus modulates the formation of actomyosin cross-bridges in a variant-specific manner. Consistent with this, a recombinant NH2-terminal peptide that excludes residues 34-59 reduces the sliding velocity of actin filaments past myosin heads from 9.0 +/- 1.3 to 5.7 +/- 1.0 m/s at 0.1 M, while a recombinant peptide that excludes residues 21-59 fails to do so. Notably, the actomyosin regulatory properties of sMyBP-C are completely abolished by the presence of the DA-1 mutations. In summary, our studies are the first to show that the NH2 and COOH termini of sMyBP-C have distinct functions, which are regulated by differential splicing, and are compromized by the presence of missense point mutations linked to muscle disease.Ackermann, M. A., Patel, P. D., Valenti, J., Takagi, Y., Homsher, E., Sellers, J. R., Kontrogiannni-Konstantopoulos, A. Loss of actomyosin regulation in distal arthrogryposis myopathy due to mutant myosin binding protein-C slow.
C1 [Ackermann, Maegen A.; Patel, Puja D.; Valenti, Jane; Kontrogianni-Konstantopoulos, Aikaterini] Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA.
[Takagi, Yasuharu; Sellers, James R.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Homsher, Earl] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USA.
RP Kontrogianni-Konstantopoulos, A (reprint author), Univ Maryland, Sch Med, 108 N Greene St, Baltimore, MD 21201 USA.
EM akons001@umaryland.edu
FU U.S. National Institutes of Health (NIH) [R01-AR-52768]; NIH (intramural
funds from National Heart, Lung, and Blood Institute); NIH
[F32-AR-058079]
FX This research has been supported by grants to A. K. K. from the U.S.
National Institutes of Health (NIH; R01-AR-52768), to J.R.S from the NIH
(intramural funds from National Heart, Lung, and Blood Institute), and
to M. A. A. from the NIH (F32-AR-058079).
NR 41
TC 13
Z9 13
U1 1
U2 4
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
EI 1530-6860
J9 FASEB J
JI Faseb J.
PD AUG
PY 2013
VL 27
IS 8
BP 3217
EP 3228
DI 10.1096/fj.13-228882
PG 12
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 292BT
UT WOS:000329877600027
PM 23657818
ER
PT J
AU Lv, JY
Wang, FS
Gao, B
AF Lv, Ji-Yun
Wang, Fu-Sheng
Gao, Bin
TI Special Issue: 7th International Symposium on Alcoholic Liver and
Pancreatic Diseases and Cirrhosis PREFACE
SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
LA English
DT Editorial Material
C1 [Lv, Ji-Yun] Beijing 302 Hosp, Beijing, Peoples R China.
[Wang, Fu-Sheng] Beijing 302 Hosp, Inst Translat Hepatol, Beijing, Peoples R China.
[Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD USA.
RP Lv, JY (reprint author), Beijing 302 Hosp, Beijing, Peoples R China.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0815-9319
EI 1440-1746
J9 J GASTROEN HEPATOL
JI J. Gastroenterol. Hepatol.
PD AUG
PY 2013
VL 28
SU 1
SI SI
BP 3
EP 3
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 286JB
UT WOS:000329463400001
ER
PT J
AU Warren, KR
Murray, MM
AF Warren, Kenneth R.
Murray, Margaret M.
TI Alcoholic liver disease and pancreatitis: Global health problems being
addressed by the US National Institute on Alcohol Abuse and Alcoholism
SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
LA English
DT Article; Proceedings Paper
CT 7th International Symposium on Alcoholic Liver and Pancreatic Diseases
and Cirrhosis
CY SEP 06-07, 2012
CL Beijing, PEOPLES R CHINA
DE NIAAA; hepatitis C; ALD; cancer
ID HEPATOCELLULAR-CARCINOMA; VIRAL-HEPATITIS; RISK-FACTORS; FATTY LIVER;
PATHOGENESIS; METAANALYSIS; SYNERGISM; INJURY
AB The review article summarizes the mission of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) with focus on the NIAAA's current and future research version for alcoholic liver disease and alcoholic pancreatitis.
C1 [Warren, Kenneth R.; Murray, Margaret M.] NIAAA, NIH, Bethesda, MD 20892 USA.
RP Warren, KR (reprint author), NIAAA, NIH, 5635 Fishers Lane, Bethesda, MD 20892 USA.
EM kwarren@willco.niaaa.nih.gov
NR 27
TC 10
Z9 10
U1 3
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0815-9319
EI 1440-1746
J9 J GASTROEN HEPATOL
JI J. Gastroenterol. Hepatol.
PD AUG
PY 2013
VL 28
SU 1
SI SI
BP 4
EP 6
DI 10.1111/jgh.12246
PG 3
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 286JB
UT WOS:000329463400002
PM 23855288
ER
PT J
AU Zakhari, S
AF Zakhari, Samir
TI Bermuda Triangle for the liver: Alcohol, obesity, and viral hepatitis
SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
LA English
DT Article; Proceedings Paper
CT 7th International Symposium on Alcoholic Liver and Pancreatic Diseases
and Cirrhosis
CY SEP 06-07, 2012
CL Beijing, PEOPLES R CHINA
DE Alcohol; viral hepatitis; liver; oxidative stress; free radicals; CYP2E1
ID UNFOLDED PROTEIN RESPONSE; VIRUS CORE PROTEIN; C VIRUS; OXIDATIVE
STRESS; FATTY LIVER; METABOLIC SYNDROME; CYP2E1 ACTIVITY; DISEASE;
ETHANOL; INJURY
AB Despite major progress in understanding and managing liver disease in the past 30 years, it is now among the top 10 most common causes of death globally. Several risk factors, such as genetics, diabetes, obesity, excessive alcohol consumption, viral infection, gender, immune dysfunction, and medications, acting individually or in concert, are known to precipitate liver damage. Viral hepatitis, excessive alcohol consumption, and obesity are the major factors causing liver injury. Estimated numbers of hepatitis B virus (HBV) and hepatitis C virus (HCV)-infected subjects worldwide are staggering (370 and 175 million, respectively), and of the 40 million known human immunodeficiency virus positive subjects, 4 and 5 million are coinfected with HBV and HCV, respectively. Alcohol and HCV are the leading causes of end-stage liver disease worldwide and the most common indication for liver transplantation in the United States and Europe. In addition, the global obesity epidemic that affects up to 40 million Americans, and 396 million worldwide, is accompanied by an alarming incidence of end-stage liver disease, a condition exacerbated by alcohol. This article focuses on the interactions between alcohol, viral hepatitis, and obesity (euphemistically described here as the Bermuda Triangle of liver disease), and discusses common mechanisms and synergy.
C1 NIAAA, Div Metab & Hlth Effects, NIH, Bethesda, MD 20892 USA.
RP Zakhari, S (reprint author), NIAAA, Div Metab & Hlth Effects, NIH, Bethesda, MD 20892 USA.
EM szakhari@mail.nih.gov
NR 47
TC 18
Z9 19
U1 0
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0815-9319
EI 1440-1746
J9 J GASTROEN HEPATOL
JI J. Gastroenterol. Hepatol.
PD AUG
PY 2013
VL 28
SU 1
SI SI
BP 18
EP 25
DI 10.1111/jgh.12207
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 286JB
UT WOS:000329463400005
PM 23855291
ER
PT J
AU Kong, XN
Feng, DC
Mathews, S
Gao, B
AF Kong, Xiaoni
Feng, Dechun
Mathews, Stephanie
Gao, Bin
TI Hepatoprotective and anti-fibrotic functions of interleukin-22:
Therapeutic potential for the treatment of alcoholic liver disease
SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
LA English
DT Article; Proceedings Paper
CT 7th International Symposium on Alcoholic Liver and Pancreatic Diseases
and Cirrhosis
CY SEP 06-07, 2012
CL Beijing, PEOPLES R CHINA
DE hepatic stellate cells; liver fibrosis; liver progenitor cells;
senescence
ID HEPATIC STELLATE CELLS; VIRUS-INFECTION; B-VIRUS; MICE; INJURY; IL-22;
ACTIVATION; PROTECTS; FIBROSIS; STAT3
AB Interleukin-22 (IL-22) plays a key role in promoting antimicrobial immunity and tissue repair at barrier surfaces by binding to the receptors IL-22R1, which is generally thought to be expressed exclusively in epithelial cells, and IL-10R2. Our laboratory previously demonstrated that IL-22 plays an important role in ameliorating liver injury in many rodent models by targeting hepatocytes that express high levels of IL-22R1 and IL-10R2. Recently, we have identified high expression levels of IL-22R1 and IL-10R2 in liver progenitor cells and hepatic stellate cells (HSCs). Overexpression of IL-22 in vivo or treatment with IL-22 in vitro promotes proliferation of liver progenitor cells via a signal transducer and activator of transcription 3 (STAT3)-dependent mechanism. IL-22 treatment also prevents HSC apoptosis in vitro and in vivo. Surprisingly, overexpression of IL-22, via either gene targeting or exogenous administration of adenovirus expressing IL-22, reduces liver fibrosis and accelerates the resolution of liver fibrosis during recovery. The anti-fibrotic effects of IL-22 are mediated via the activation of STAT3 in HSCs and subsequent induction of suppressor of cytokine signaling 3, which induces HSC senescence. Taken together, the hepatoprotective, mitogenic, and anti-fibrotic effects of IL-22 are beneficial in ameliorating alcoholic liver injury. Importantly, due to the restricted expression of IL-22R1, IL-22 therapy is expected to have few side effects, thus making IL-22 a potential candidate for treatment of alcoholic liver disease.
C1 [Kong, Xiaoni; Feng, Dechun; Mathews, Stephanie; Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD USA.
[Kong, Xiaoni] Shanghai Jiao Tong Univ, Sch Biomed Engn, Shanghai 200030, Peoples R China.
[Kong, Xiaoni] Shanghai Jiao Tong Univ, Med X Res Inst, Shanghai 200030, Peoples R China.
RP Kong, XN (reprint author), Shanghai Jiao Tong Univ, Sch Biomed Engn, 1954 Huashan Rd, Shanghai 200030, Peoples R China.
EM xiaonikong@sjtu.edu.cn
RI Feng, Dechun/Q-5962-2016
FU NIAAA, NIH
FX This work was supported by the Intramural Program of NIAAA, NIH.
NR 46
TC 19
Z9 21
U1 0
U2 15
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0815-9319
EI 1440-1746
J9 J GASTROEN HEPATOL
JI J. Gastroenterol. Hepatol.
PD AUG
PY 2013
VL 28
SU 1
SI SI
BP 56
EP 60
DI 10.1111/jgh.12032
PG 5
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 286JB
UT WOS:000329463400011
PM 23855297
ER
PT J
AU Havla, J
Berthele, A
Kumpfel, T
Krumbholz, M
Jochim, A
Kronsbein, H
Ryschkewitsch, C
Jensen, P
Lippmann, K
Hemmer, B
Major, E
Hohlfeld, R
AF Havla, J.
Berthele, A.
Kuempfel, T.
Krumbholz, M.
Jochim, A.
Kronsbein, H.
Ryschkewitsch, C.
Jensen, P.
Lippmann, K.
Hemmer, B.
Major, E.
Hohlfeld, R.
TI Co-occurrence of two cases of progressive multifocal leukoencephalopathy
in a natalizumab "infusion group"
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Article
DE Natalizumab; multiple sclerosis; progressive multifocal
leukoencephalopathy; PML; JC virus
ID POLYOMAVIRUS JC-VIRUS; PATIENT
AB We observed two cases of progressive multifocal leukoencephalopathy (PML) that occurred in the same infusion group. The group consisted of four patients with relapsing-remitting multiple sclerosis (RRMS) who had been treated with natalizumab (NAT) in the same medical practice for more than four years at the same times and in the same room, raising concerns about viral transmission between members of the infusion group. DNA amplification and sequence comparison of the non-coding control region (NCCR) of JC virus (JCV) present in cerebrospinal fluid (CSF) samples from PML patients #1 and #2 revealed that the amplified JCV sequences differed from the JCV archetype. The NCRR of the viral DNA was unique to each patient, arguing against the possibility of viral transmission between patients. Statistical considerations predict that similar co-occurrences of PML are likely to happen in the future.
C1 [Havla, J.; Kuempfel, T.; Krumbholz, M.; Hohlfeld, R.] Univ Munich, Inst Clin Neuroimmunol, Munich, Germany.
[Berthele, A.; Jochim, A.; Kronsbein, H.; Hemmer, B.] Tech Univ Munich, Dept Neurol, D-80290 Munich, Germany.
[Ryschkewitsch, C.; Jensen, P.; Major, E.] NIH, Mol Med Lab, Bethesda, MD USA.
RP Hohlfeld, R (reprint author), Klinikum LMU Munchen, Inst Clin Neuroimmunol, Campus Grosshadern,Marchioninistr 15, D-81377 Munich, Germany.
EM reinhard.hohlfeld@med.uni-muenchen.de
FU Deutsche Forschungsgemeinschaft [SFB / TR 128]; Bayer-Schering AG;
Bayer; Deutsche Forschungsgemeinschaft, Bundesministerium fur Bildung
und Forschung (BMBF-KKNMS); Novartis; Biogen Idec; Merck-Serono;
Metanomics; Protagen AG
FX R.H. is supported by the Deutsche Forschungsgemeinschaft (SFB / TR 128)
and by the Deutsche Forschungsgemeinschaft, Bundesministerium fur
Bildung und Forschung (BMBF-KKNMS) and has received personal
compensations from Bayer Schering Pharmacy, Teva, Merck-Serono, Biogen
Idec and Novartis. T. K. has received travel expenses and personal
compensations from Bayer Schering Pharmacy, Teva, Sanofi-Aventis,
Novartis, Merck-Serono and Biogen Idec as well as grant support from
Bayer-Schering AG. J.H. received travel expenses and personal
compensations from Merck-Serono, Teva, Bayer Schering, Novartis and
Biogen Idec. C. R, P.J and E. M have no conflicts nor anything to
report. A. B. has received travel expenses and personal compensations
from Biogen Idec, Bayer, Teva and Novartis and grant support from Bayer.
B. H. is supported by the Deutsche Forschungsgemeinschaft,
Bundesministerium fur Bildung und Forschung (BMBF-KKNMS), and Hertie
Foundation, has received personal compensations from Hoffmann la Roche,
Merck-Serono, Biogen Idec, Novartis and Bayer. He serves as a consultant
for Gerson Lehrman Group, and has received grant support from Novartis,
Biogen Idec, Merck-Serono, Bayer, Metanomics and Protagen AG. A.J. has
received travel expenses from Merck-Serono, Bayer, Teva,
GlaxoSmithKline, Allergan and Abbott. H. K. has received travel expenses
from Merck-Serono. K.L. reports no disclosures.
NR 5
TC 7
Z9 7
U1 0
U2 1
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1352-4585
EI 1477-0970
J9 MULT SCLER J
JI Mult. Scler. J.
PD AUG
PY 2013
VL 19
IS 9
BP 1213
EP 1215
DI 10.1177/1352458512466165
PG 3
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 287WT
UT WOS:000329573700016
PM 23124790
ER
PT J
AU Henrich, CJ
Budhu, A
Yu, ZP
Evans, JR
Goncharova, EI
Ransom, TT
Wang, XW
McMahon, JB
AF Henrich, Curtis J.
Budhu, Anuradha
Yu, Zhipeng
Evans, Jason R.
Goncharova, Ekaterina I.
Ransom, Tanya T.
Wang, Xin W.
McMahon, James B.
TI High-throughput Screening for Identification of Inhibitors of
EpCAM-Dependent Growth of Hepatocellular Carcinoma Cells
SO CHEMICAL BIOLOGY & DRUG DESIGN
LA English
DT Article
DE hepatocellular carcinoma; epithelial cell adhesion molecule; Wnt;
-catenin; high-throughput screening
ID CANCER STEM-CELLS; PATHWAY; ANTIGEN; MARKER; LINES
AB The cancer stem cell marker, EpCAM, is an important indicator of Wnt/-catenin signaling activation and a functional component of hepatocellular tumor-initiating cells. A high-throughput screening assay was developed to identify inhibitors of EpCAM-dependent growth of hepatocellular carcinoma (HCC) cells. EpCAM(+) and EpCAM(-) HCC cell lines were assessed for differential sensitivity to a Wnt/-catenin pathway inhibitor. Libraries comprising 22668 pure compounds and 107741 crude or partially purified natural product extracts were tested, and 12 pure compounds and 67 natural product extracts were identified for further study. Three active compounds and the positive control were further characterized in terms of effects on EpCAM expression. Treatment of EpCAM(+) Hep3B cells resulted in loss of EpCAM expression as assessed by flow cytometry. This reduction was incomplete (most cells continued to express EpCAM), but resulted in generation of cell populations expressing lower levels of EpCAM. Sublethal concentrations (similar to IC50) reduced median EpCAM expression to 28% of control after 1day and 19% of control after 2days. Reduction in EpCAM expression preceded growth inhibition suggesting that a threshold of EpCAM expression may be required for growth of EpCAM-dependent cells. The identification of compounds with a variety of possible molecular targets suggests a likelihood of multiple mechanisms for modulation of EpCAM-dependent cell growth.
C1 [Henrich, Curtis J.; Evans, Jason R.; Goncharova, Ekaterina I.; Ransom, Tanya T.; McMahon, James B.] NCI, Mol Targets Lab, Frederick, MD 21701 USA.
[Henrich, Curtis J.] SAIC Frederick Inc, Basic Sci Program, Frederick, MD USA.
[Budhu, Anuradha; Yu, Zhipeng; Wang, Xin W.] NCI, Liver Carcinogenesis Sect, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Evans, Jason R.; Goncharova, Ekaterina I.] Data Management Serv Inc, Frederick, MD USA.
RP Henrich, CJ (reprint author), NCI, Mol Targets Lab, Frederick, MD 21701 USA.
EM henrichcj@mail.nih.gov
RI Wang, Xin/B-6162-2009
FU Frederick National Laboratory for Cancer Research, National Institutes
of Health [HHSN261200800001E]; NIH; Frederick National Lab; Center for
Cancer Research; National Cancer Institute [Z01 BC 010876, ZIC BC
010469]
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. This research was supported in part by the Intramural
Research Program of NIH, Frederick National Lab, the Center for Cancer
Research, the National Cancer Institute (Z01 BC 010876 and ZIC BC
010469).
NR 22
TC 6
Z9 6
U1 1
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1747-0277
EI 1747-0285
J9 CHEM BIOL DRUG DES
JI Chem. Biol. Drug Des.
PD AUG
PY 2013
VL 82
IS 2
BP 131
EP 139
DI 10.1111/cbdd.12146
PG 9
WC Biochemistry & Molecular Biology; Chemistry, Medicinal
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA 283WC
UT WOS:000329276700002
PM 23879724
ER
PT J
AU Rienhoff, HY
Yeo, CY
Morissette, R
Khrebtukova, I
Melnick, J
Luo, SJ
Leng, N
Kim, YJ
Schroth, G
Westwick, J
Vogel, H
McDonnell, N
Hall, JG
Whitman, M
AF Rienhoff, Hugh Young, Jr.
Yeo, Chang-Yeol
Morissette, Rachel
Khrebtukova, Irina
Melnick, Jonathan
Luo, Shujun
Leng, Nan
Kim, Yeon-Jin
Schroth, Gary
Westwick, John
Vogel, Hannes
McDonnell, Nazli
Hall, Judith G.
Whitman, Malcolm
TI A Mutation in TGFB3 Associated With a Syndrome of Low Muscle Mass,
Growth Retardation, Distal Arthrogryposis and Clinical Features
Overlapping With Marfan and Loeys-Dietz Syndrome
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
DE transforming growth factor beta; Marfan syndrome; Loeys-Dietz syndrome;
distal arthrogryposis; low muscle mass; bifid uvula; exome sequencing;
de novo mutation; hyomyoplasia
ID CRYSTAL-STRUCTURE; SATELLITE CELLS; TGF-BETA-1; MYOSTATIN; PATTERNS;
DIFFERENTIATION; SUPERFAMILY; PROGENITORS; PRECURSORS; EXPRESSION
AB The transforming growth factor beta (TGF-beta) family of growth factors are key regulators of mammalian development and their dysregulation is implicated in human disease, notably, heritable vasculopathies including Marfan (MFS, OMIM #154700) and Loeys-Dietz syndromes (LDS, OMIM #609192). We described a syndrome presenting at birth with distal arthrogryposis, hypotonia, bifid uvula, a failure of normal post-natal muscle development but no evidence of vascular disease; some of these features overlap with MFS and LDS. A de novo mutation in TGFB3 was identified by exome sequencing. Several lines of evidence indicate the mutation is hypomorphic suggesting that decreased TGF-beta signaling from a loss of TGFB3 activity is likely responsible for the clinical phenotype. This is the first example of a mutation in the coding portion of TGFB3 implicated in a clinical syndrome suggesting TGFB3 is essential for both human palatogenesis and normal muscle growth. Copyright (C) 2013 Wiley Periodicals, Inc.
C1 [Rienhoff, Hugh Young, Jr.] Childrens Hosp Oakland Res Inst, Oakland, CA USA.
[Yeo, Chang-Yeol; Kim, Yeon-Jin] Ewha Womans Univ, Dept Life Sci, Seoul, South Korea.
[Morissette, Rachel; McDonnell, Nazli] NIA, NIH, Baltimore, MD 21224 USA.
[Khrebtukova, Irina; Luo, Shujun; Leng, Nan; Schroth, Gary] Illumina Inc, Hayward, CA USA.
[Melnick, Jonathan; Westwick, John] Odyssey Thera Inc, San Ramon, CA USA.
[Vogel, Hannes] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA.
[Hall, Judith G.] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada.
[Whitman, Malcolm] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA.
RP Rienhoff, HY (reprint author), Childrens Hosp Oakland Res Inst, 2729 Debbie Court, San Carlos, CA 94070 USA.
EM hrienhoff@datahooks.com
OI Vogel, Otto Hannes/0000-0002-0960-3508; Yeo,
Chang-Yeol/0000-0002-4440-1215
FU Intramural Research Program of the National Institutes of Health,
National Institutes of Aging; National Research Foundation of Korea
[20090-0076374]
FX Grant sponsor: Intramural Research Program of the National Institutes of
Health, National Institutes of Aging; Grant sponsor: National Research
Foundation of Korea; Grant number: 20090-0076374.
NR 23
TC 27
Z9 28
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4825
EI 1552-4833
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD AUG
PY 2013
VL 161
IS 8
BP 2040
EP 2046
DI 10.1002/ajmg.a.36056
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 263EM
UT WOS:000327789600031
PM 23824657
ER
PT J
AU Krause, CE
Otieno, BA
Latus, A
Faria, RC
Patel, V
Gutkind, JS
Rusling, JF
AF Krause, Colleen E.
Otieno, Brunah A.
Latus, Alina
Faria, Ronaldo C.
Patel, Vyomesh
Gutkind, J. Silvio
Rusling, James F.
TI Rapid Microfluidic Immunoassays of Cancer Biomarker Proteins Using
Disposable Inkjet-Printed Gold Nanoparticle Arrays
SO CHEMISTRYOPEN
LA English
DT Article
DE cancer biomarkers; electrochemistry; inkjet-printed arrays;
microfluidics; sensors
ID SENTINEL NODE BIOPSY; WHOLE-BODY MRI; NECK-CANCER; ULTRASENSITIVE
DETECTION; SERUM; HEAD; INTERLEUKIN-8; PROTEOMICS; DIAGNOSIS; PET/CT
C1 [Krause, Colleen E.; Otieno, Brunah A.; Latus, Alina; Rusling, James F.] Univ Connecticut, Dept Chem, Storrs, CT USA.
[Latus, Alina] I Murgulescu Romanian Acad Splaiul, Inst Phys Chem, Bucharest 060021, Romania.
[Faria, Ronaldo C.] Univ Fed Sao Carlos, Dept Quim, Sao Paulo, Brazil.
[Patel, Vyomesh; Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, NIH, Pharyngeal Canc Branch, Bethesda, MD USA.
[Rusling, James F.] Univ Connecticut, Ctr Hlth, Dept Cell Biol, Farmington, CT USA.
[Rusling, James F.] Natl Univ Ireland Galway, Dept Chem, Galway, Ireland.
RP Krause, CE (reprint author), Univ Connecticut, Dept Chem, U-60, Storrs, CT USA.
EM james.rusling@uconn.edu
RI Faria, Ronaldo/B-4130-2008
OI Faria, Ronaldo/0000-0003-1094-9597
FU National Institute of Biomedical Imaging and Bioengineering (NIBIB), US
National Institutes of Health (NIH) [EB014586]; National Institute of
Dental and Craniofacial Research (NIDCR), NIH
FX This work was financially supported by the National Institute of
Biomedical Imaging and Bioengineering (NIBIB), US National Institutes of
Health (NIH) (grant no. EB014586). Partial support was provided by the
Intramural Research Program, National Institute of Dental and
Craniofacial Research (NIDCR), NIH. Our thanks to Dr. Naimish Sardesai
(University of Connecticut) for his help imaging AuNPs with TEM.
NR 35
TC 19
Z9 19
U1 4
U2 47
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY
SN 2191-1363
J9 CHEMSTRYOPEN
JI ChemistryOpen
PD AUG
PY 2013
VL 2
IS 4
BP 141
EP 145
DI 10.1002/open.201300018
PG 5
WC Chemistry, Multidisciplinary
SC Chemistry
GA 274NT
UT WOS:000328613900002
PM 24482763
ER
PT J
AU Glass, RI
AF Glass, Roger I.
TI Beyond Discovering the Viral Agents of Acute Gastroenteritis
SO EMERGING INFECTIOUS DISEASES
LA English
DT Editorial Material
C1 [Glass, Roger I.] NIH, Bethesda, MD 20892 USA.
RP Glass, RI (reprint author), NIH, Fogarty Int Ctr, 31 Ctr Dr,Mailstop C2220, Bethesda, MD 20892 USA.
EM glassr@mail.nih.gov
NR 0
TC 8
Z9 8
U1 0
U2 1
PU CENTERS DISEASE CONTROL
PI ATLANTA
PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA
SN 1080-6040
EI 1080-6059
J9 EMERG INFECT DIS
JI Emerg. Infect. Dis
PD AUG
PY 2013
VL 19
IS 8
BP 1190
EP 1191
DI 10.3201/eid1908.130773
PG 2
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 268MA
UT WOS:000328173700002
PM 23876318
ER
PT J
AU Sturm, EM
Dyer, KD
Percopo, CM
Heinemann, A
Rosenberg, HF
AF Sturm, Eva M.
Dyer, Kimberly D.
Percopo, Caroline M.
Heinemann, Akos
Rosenberg, Helene F.
TI Chemotaxis of bone marrow derived eosinophils in vivo: A novel method to
explore receptor-dependent trafficking in the mouse
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Article
DE Bone morrow derived eosinophils; CCL24; Chemotaxis; Immunology; Mouse
model
ID HUMAN CC-CHEMOKINE; AIRWAY INFLAMMATION; BIOLOGICAL-PROPERTIES;
EOTAXIN-2; ASTHMA; HYPERRESPONSIVENESS; DISEASE; MICE; RECRUITMENT;
MIGRATION
AB Here, we describe a novel method via which ex vivo cultured mouse bone marrow derived eosinophils (bmEos) can be adoptively transferred into recipient mice in order to study receptor-dependent recruitment to lung tissue in vivo. Intratracheal instillation of recombinant human eotaxin-2 (hCCL24) prior to introduction of bmEos via tail vein injection resulted in an approximately fourfold increase in Siglec F-positive/CD11c-negative eosinophils in the lungs of eosinophil-deficient dblGATA recipient mice compared with controls. As anticipated, bmEos generated from CCR3-gene-deleted mice did not migrate to the lung in response to hCCL24 in this model, indicating specific receptor dependence. BmEos generated from GFP-positive BALB/c mice responded similarly to hCCL24 in vitro and were detected in lung tissue of BALB/c WT as well as BALB/c dblGATA eosinophil-deficient recipient mice, at approximately fourfold (at 5 h post-injection) and approximately threefold (at 24 h postinjection) over baseline, respectively. Comparable results were obtained with GFP-positive C57BL/6 bmEos responding to intratracheal hCCL24 in C57BL/6 dblGATA recipient mice. The use of ex vivo cultured bmEos via one or more of these methods offers the possibility of manipulating bmEos prior to transfer into a WT or gene-deleted recipient host. Thus, this chemotaxis model represents a novel and robust tool for pharmacological studies in vivo.
C1 [Sturm, Eva M.; Dyer, Kimberly D.; Percopo, Caroline M.; Rosenberg, Helene F.] NIAID, Inflammat Immunobiol Sect, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
[Sturm, Eva M.; Heinemann, Akos] Med Univ Graz, Inst Expt & Clin Pharmacol, A-8010 Graz, Austria.
RP Sturm, EM (reprint author), Med Univ Graz, Inst Expt & Clin Pharmacol, Univ Pl 4, A-8010 Graz, Austria.
EM eva.sturm@medunigraz.at
OI Heinemann, Akos/0000-0002-8554-2372
FU Erwin-Schrodinger Fellowship of the Austrian Science Fund FWF
[J3235-B11]; NIAID Division of Intramural Research [AI000941]
FX E.M.S was funded by the Erwin-Schrodinger Fellowship of the Austrian
Science Fund FWF (Grant J3235-B11). This work was supported by the NIAID
Division of Intramural Research (#AI000941 to H.F.R.). The authors thank
the staff of the 14BS animal facility of the NIAID for instruction on
intravenous inoculation procedures, as well as for care of the mice used
in these experiments.
NR 38
TC 1
Z9 1
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0014-2980
EI 1521-4141
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD AUG
PY 2013
VL 43
IS 8
BP 2217
EP 2228
DI 10.1002/eji.201343371
PG 12
WC Immunology
SC Immunology
GA 277SN
UT WOS:000328839700024
PM 23670593
ER
PT J
AU Jaffe, ES
AF Jaffe, Elaine S.
TI Follicular lymphomas: a tapestry of common and contrasting threads
SO HAEMATOLOGICA
LA English
DT Editorial Material
ID BCL2 GENE TRANSLOCATION; CENTER B-CELLS; YOUNG-ADULTS; GRADE 3B;
CHILDREN; PATHOGENESIS; MUTATIONS; PROGNOSIS; DISEASE
C1 NCI, Hematopathol Sect, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Jaffe, ES (reprint author), NCI, Hematopathol Sect, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
EM ejaffe@mail.nih.gov
OI Jaffe, Elaine/0000-0003-4632-0301
NR 23
TC 3
Z9 4
U1 0
U2 2
PU FERRATA STORTI FOUNDATION
PI PAVIA
PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
SN 0390-6078
J9 HAEMATOLOGICA
JI Haematologica
PD AUG
PY 2013
VL 98
IS 8
BP 1163
EP 1165
DI 10.3324/haematol.2013.086678
PG 3
WC Hematology
SC Hematology
GA 273NI
UT WOS:000328541500009
PM 23904232
ER
PT J
AU Mo, CC
Njuguna, N
Beum, PV
Lindorfer, MA
Vire, B
Lee, E
Marti, G
Wilson, WH
Taylor, RP
Wiestner, A
AF Mo, Clifton C.
Njuguna, Ndegwa
Beum, Paul V.
Lindorfer, Margaret A.
Vire, Berengere
Lee, Elinor
Marti, Gerald
Wilson, Wyndham H.
Taylor, Ronald P.
Wiestner, Adrian
TI Rapid clearance of rituximab may contribute to the continued high
incidence of autoimmune hematologic complications of chemoimmunotherapy
for chronic lymphocytic leukemia
SO HAEMATOLOGICA
LA English
DT Article
ID HEMOLYTIC-ANEMIA; DOSE RITUXIMAB; FLUDARABINE; THERAPY;
CYCLOPHOSPHAMIDE; LYMPHOMA; ANTIBODY; COMBINATION; DISEASE; CELLS
AB Rituximab is an effective treatment for autoimmune cytopenias associated with chronic lymphocytic leukemia. Despite the incorporation of rituximab into fludarabine-based chemotherapy regimens, the incidence of autoimmune cytopenias has remained high. Inadequate rituximab exposure due to rapid antibody clearance may be a contributing factor. To test this hypothesis, we measured serum rituximab levels in patients treated with fludarabine and rituximab (375 mg/m(2)). All patients had undetectable rituximab trough levels by the end of cycle 1, and one-third had undetectable levels already on Day 6 of cycle 1. Although rituximab trough levels increased progressively with each cycle, only by cycle 4 did the median trough level exceed 10 ug/mL. The median half-life of rituximab during cycle 1 was 27 hours, compared to 199 hours during cycle 4 (P<0.0001). There was a significant inverse correlation between the rituximab half-life in cycle 1 and the degree of tumor burden (P=0.02). Two patients who were identified as having subclinical autoimmune hemolysis prior to therapy were given additional doses of rituximab during the initial cycles of therapy and did not develop clinically significant hemolysis. One patient who developed clinically significant hemolysis during therapy was given additional rituximab doses during cycles 3-5 and was able to successfully complete his treatment. In conclusion, rituximab is cleared so rapidly during the initial cycles of therapy for chronic lymphocytic leukemia that most patients have only transient serum levels. More frequent dosing of rituximab may be required to prevent autoimmune complications in at-risk patients (clinicaltrials.gov identifier:00001586).
C1 [Mo, Clifton C.; Njuguna, Ndegwa; Vire, Berengere; Lee, Elinor; Marti, Gerald; Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Mo, Clifton C.] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA.
[Beum, Paul V.; Lindorfer, Margaret A.; Taylor, Ronald P.] Univ Virginia, Sch Med, Dept Biochem & Mol Genet, Charlottesville, VA 22908 USA.
[Wilson, Wyndham H.] NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Wiestner, A (reprint author), NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
EM wiestnera@mail.nih.gov
FU NIH, the National, Heart, Lung and Blood Institute; National Cancer
Institute
FX This research was supported by the Intramural Research Program of the
NIH, the National, Heart, Lung and Blood Institute, and the National
Cancer Institute.
NR 27
TC 4
Z9 4
U1 0
U2 0
PU FERRATA STORTI FOUNDATION
PI PAVIA
PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
SN 0390-6078
J9 HAEMATOLOGICA
JI Haematologica
PD AUG
PY 2013
VL 98
IS 8
BP 1259
EP 1263
DI 10.3324/haematol.2012.080929
PG 5
WC Hematology
SC Hematology
GA 273NI
UT WOS:000328541500022
PM 23716541
ER
PT J
AU Mast, AE
Schlumpf, KS
Wright, DJ
Johnson, B
Glynn, SA
Busch, MP
Olbina, G
Westerman, M
Nemeth, E
Ganz, T
AF Mast, Alan E.
Schlumpf, Karen S.
Wright, David J.
Johnson, Bryce
Glynn, Simone A.
Busch, Michael P.
Olbina, Gordana
Westerman, Mark
Nemeth, Elizabeta
Ganz, Tomas
CA NHLBI Retrovirus Epidemiology Dono
TI Hepcidin level predicts hemoglobin concentration in individuals
undergoing repeated phlebotomy
SO HAEMATOLOGICA
LA English
DT Article
ID STATUS EVALUATION RISE; BLOOD-DONORS; IRON-DEFICIENCY; OVERLOAD;
MINIHEPCIDINS; DONATION; STORES; MICE
AB Dietary iron absorption is regulated by hepcidin, an iron regulatory protein produced by the liver. Hepcidin production is regulated by iron stores, erythropoiesis and inflammation, but its physiology when repeated blood loss occurs has not been characterized. Hepcidin was assayed in plasma samples obtained from 114 first-time/reactivated (no blood donations in preceding 2 years) female donors and 34 frequent (>= 3 red blood cell donations in preceding 12 months) male donors as they were phlebotomized >= 4 times over 18-24 months. Hepcidin levels were compared to ferritin and hemoglobin levels using multivariable repeated measures regression models. Hepcidin, ferritin and hemoglobin levels declined with increasing frequency of donation in the first-time/reactivated females. Hepcidin and ferritin levels correlated well with each other (Spearman's correlation of 0.74), but on average hepcidin varied more between donations for a given donor relative to ferritin. In a multivariable repeated measures regression model the predicted inter-donation decline in hemoglobin varied as a function of hepcidin and ferritin; hemoglobin was 0.51 g/dL lower for subjects with low (<= 45.7 ng/mL) or decreasing hepcidin and low ferritin (<= 26 ng/mL), and was essentially zero for other subjects including those with high (>45.7 ng/mL) or increasing hepcidin and low ferritin (<= 26 ng/mL) levels (P<0.001). In conclusion, hepcidin levels change rapidly in response to dietary iron needed for erythropoiesis. The dynamic regulation of hepcidin in the presence of a low levels of ferritin suggests that plasma hepcidin concentration may provide clinically useful information about an individual's iron status (and hence capacity to tolerate repeated blood donations) beyond that of ferritin alone.
C1 [Mast, Alan E.] Blood Ctr Wisconsin, Blood Res Inst, Milwaukee, WI USA.
[Mast, Alan E.] Med Coll Wisconsin, Dept Cell Biol Neurobiol & Anat, Milwaukee, WI 53226 USA.
[Schlumpf, Karen S.; Wright, David J.; Johnson, Bryce] WESTAT Corp, Rockville, MD USA.
[Glynn, Simone A.] NHLBI, Transfus Med & Cellular Therapies, Bethesda, MD 20892 USA.
[Busch, Michael P.] Blood Syst Res Inst, San Francisco, CA USA.
[Olbina, Gordana; Westerman, Mark] Intrins LifeSci LLC, La Jolla, CA USA.
[Nemeth, Elizabeta; Ganz, Tomas] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
[Nemeth, Elizabeta; Ganz, Tomas] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol, Los Angeles, CA 90095 USA.
RP Mast, AE (reprint author), Blood Ctr Wisconsin, Blood Res Inst, Milwaukee, WI USA.
EM alan.mast@bcw.edu
FU NHLBI [N01-HB-47168, N01-HB-47169, N01-HB-47170, N01-HB-47171,
N01-HB-47172, N01-HB-47174, N01-HB-47175, N01-HB-57181]
FX This work was supported by NHLBI contracts N01-HB-47168, -47169, -47170,
-47171, -47172, -47174, -47175, and -57181.
NR 22
TC 12
Z9 12
U1 0
U2 2
PU FERRATA STORTI FOUNDATION
PI PAVIA
PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
SN 0390-6078
J9 HAEMATOLOGICA
JI Haematologica
PD AUG
PY 2013
VL 98
IS 8
BP 1324
EP 1330
DI 10.3324/haematol.2012.070979
PG 7
WC Hematology
SC Hematology
GA 273NI
UT WOS:000328541500030
PM 23445875
ER
PT J
AU Sokolov, M
Neumann, R
AF Sokolov, Mykyta
Neumann, Ronald
TI Lessons Learned about Human Stem Cell Responses to Ionizing Radiation
Exposures: A Long Road Still Ahead of Us
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Review
DE human embryonic stem cells; human adult stem cells; ionizing radiation;
radiation toxicity
ID MESENCHYMAL STROMAL CELLS; HUMAN HEMATOPOIETIC STEM; DNA-DAMAGE
RESPONSE; NORMAL HUMAN FIBROBLASTS; HISTONE GENE-EXPRESSION;
SELF-RENEWAL; BONE-MARROW; HOMOLOGOUS RECOMBINATION; DIFFERENTIATED
PROGENY; HUMAN BLASTOCYSTS
AB Human stem cells (hSC) possess several distinct characteristics that set them apart from other cell types. First, hSC are self-renewing, capable of undergoing both asymmetric and symmetric cell divisions. Second, these cells can be coaxed to differentiate into various specialized cell types and, as such, hold great promise for regenerative medicine. Recent progresses in hSC biology fostered the characterization of the responses of hSC to genotoxic stresses, including ionizing radiation (IR). Here, we examine how different types of hSC respond to IR, with a special emphasis on their radiosensitivity, cell cycle, signaling networks, DNA damage response (DDR) and DNA repair. We show that human embryonic stem cells (hESCs) possess unique characteristics in how they react to IR that clearly distinguish these cells from all adult hSC studied thus far. On the other hand, a manifestation of radiation injuries/toxicity in human bodies may depend to a large extent on hSC populating corresponding tissues, such as human mesenchymal stem cells (hMSC), human hematopoietic stem cells (hHSC), neural hSC, intestine hSC, etc. We discuss here that hSC responses to IR differ notably across many types of hSC which may represent the distinct roles these cells play in development, regeneration and/or maintenance of homeostasis.
C1 [Sokolov, Mykyta; 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, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM sokolovm@mail.nih.gov; rneumann@mail.nih.gov
FU Clinical Center National Institutes of Health
FX This work was supported in part by the Intramural Research Program at
the Clinical Center National Institutes of Health.
NR 140
TC 15
Z9 17
U1 2
U2 15
PU MDPI AG
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
SN 1422-0067
J9 INT J MOL SCI
JI Int. J. Mol. Sci.
PD AUG
PY 2013
VL 14
IS 8
BP 15695
EP 15723
DI 10.3390/ijms140815695
PG 29
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
SC Biochemistry & Molecular Biology; Chemistry
GA 272ZE
UT WOS:000328501300026
PM 23899786
ER
PT J
AU Hsiao, CP
Araneta, M
Wang, XM
Saligan, LN
AF Hsiao, Chao-Pin
Araneta, Maria
Wang, Xiao Min
Saligan, Leorey N.
TI The Association of IFI27 Expression and Fatigue Intensification during
Localized Radiation Therapy: Implication of a Para-Inflammatory
Bystander Response
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE fatigue; gene expression; interferon; prostate cancer; radiation
ID BREAST-CANCER SURVIVORS; PROSTATE-CANCER; INTERFERON-ALPHA; SLEEP
DISTURBANCE; DOSE-ESCALATION; RADIOTHERAPY; CHEMOTHERAPY; DEPRESSION;
BIOMARKERS; CARCINOMA
AB The mechanisms behind fatigue intensification during cancer therapy remain elusive. The interferon alpha-inducible protein 27 (IFI27) was the most up-regulated gene based on our previous microarray data in fatigued men with non-metastatic prostate cancer receiving localized external beam radiation therapy (EBRT). The purpose of this study was to confirm the IFI27 up-regulation and determine its association with fatigue intensification during EBRT. Peripheral blood samples and fatigue scores were collected at three time pointsprior to EBRT, at midpoint, and at completion of EBRT. Confirmatory quantitative real time polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA) were utilized to verify the microarray results. Subjects were a total of 40 Caucasian men with prostate cancer; 20 scheduled for EBRT (65.6 +/- 7.5 years old), and 20 on active surveillance as controls (62.8 +/- 6.1 years old). Significant IFI27 expression overtime during EBRT was confirmed by qPCR (p < 0.5), which correlated with fatigue scores during EBRT (R = -0.90, p = 0.006). Alterations in mechanisms associated with immune response and mitochondrial function that explain the up-regulation of IFI27 may provide an understanding of the pathways related to the intensification of fatigue during localized radiation therapy.
C1 [Hsiao, Chao-Pin] Case Western Reserve Univ, Frances Payne Bolton Sch Nursing, Cleveland, OH 44106 USA.
[Hsiao, Chao-Pin; Araneta, Maria; Wang, Xiao Min; Saligan, Leorey N.] NINR, NIH, Bethesda, MD 20892 USA.
RP Saligan, LN (reprint author), NINR, NIH, 9000 Rockville Pike,Bldg 10,Room 2-1339, Bethesda, MD 20892 USA.
EM hsiaochaopin@gmail.com; maria.araneta@nih.gov; xmwang@mail.nih.gov;
saliganl@mail.nih.gov
FU National Institute of Nursing Research of the National Institutes of
Health, Bethesda, Maryland [09-NR-0088]
FX This study is fully supported by the Intramural Research Program of the
National Institute of Nursing Research of the National Institutes of
Health, Bethesda, Maryland (Protocol # 09-NR-0088). We appreciate the
guidance of Dan Wang, especially in serving as resource during the qPCR
and ELISA experiments. We also would like to thank Joan Austin and
Brigit Sullivan, Biomedical Librarian, National Institutes of Health
(NIH) Library Writing Center, for editing assistance.
NR 42
TC 12
Z9 12
U1 0
U2 9
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 AUG
PY 2013
VL 14
IS 8
BP 16943
EP 16957
DI 10.3390/ijms140816943
PG 15
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
SC Biochemistry & Molecular Biology; Chemistry
GA 272ZE
UT WOS:000328501300089
PM 23959120
ER
PT J
AU Li, F
Patterson, AD
Krausz, KW
Jiang, CT
Bi, HC
Sowers, AL
Cook, JA
Mitchell, JB
Gonzalez, FJ
AF Li, Fei
Patterson, Andrew D.
Krausz, Kristopher W.
Jiang, Changtao
Bi, Huichang
Sowers, Anastasia L.
Cook, John A.
Mitchell, James B.
Gonzalez, Frank J.
TI Metabolomics Reveals That Tumor Xenografts Induce Liver Dysfunction
SO MOLECULAR & CELLULAR PROTEOMICS
LA English
DT Article
ID ACTIVATED RECEPTOR-ALPHA; ASYMMETRIC DIMETHYLARGININE;
IONIZING-RADIATION; OXIDATIVE STRESS; GASTRIC-CANCER; IN-VIVO; MICE;
BIOMARKERS; METABOLISM; URINE
AB Metabolomics, based on ultraperformance liquid chromatography coupled with electrospray ionization quadrupole mass spectrometry, was used to explore metabolic signatures of tumor growth in mice. Urine samples were collected from control mice and mice injected with squamous cell carcinoma (SCCVII) tumor cells. When tumors reached approximate to 2 cm, all mice were killed and blood and liver samples collected. The urine metabolites hexanoylglycine, nicotinamide 1-oxide, and 11,20-dihydroxy-3-oxopregn-4-en-21-oic acid were elevated in tumor-bearing mice, as was asymmetric dimethylarginine, a biomarker for oxidative stress. Interestingly, SCCVII tumor growth resulted in hepatomegaly, reduced albumin/globulin ratios, and elevated serum triglycerides, suggesting liver dysfunction. Alterations in liver metabolites between SCCVII-tumor-bearing and control mice confirmed the presence of liver injury. Hepatic mRNA analysis indicated that inflammatory cytokines, tumor necrosis factor , and transforming growth factor were enhanced in SCCVII-tumor-bearing mice, and the expression of cytochromes P450 was decreased in tumor-bearing mice. Further, genes involved in fatty acid oxidation were decreased, suggesting impaired fatty acid oxidation in SCCVII-tumor-bearing mice. Additionally, activated phospholipid metabolism and a disrupted tricarboxylic acid cycle were observed in SCCVII-tumor-bearing mice. These data suggest that tumor growth imposes a global inflammatory response that results in liver dysfunction and underscore the use of metabolomics to temporally examine these changes and potentially use metabolite changes to monitor tumor treatment response.
C1 [Li, Fei; Patterson, Andrew D.; Krausz, Kristopher W.; Jiang, Changtao; Bi, Huichang; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Patterson, Andrew D.] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA.
[Patterson, Andrew D.] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA.
[Cook, John A.; Mitchell, James B.] NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM gonzalef@mail.nih.gov
RI Li, Fei/F-6849-2013; Patterson, Andrew/G-3852-2012
OI Patterson, Andrew/0000-0003-2073-0070
FU Intramural Research Program of the Center for Cancer Research, NCI,
National Institutes of Health
FX This work was supported in part by the Intramural Research Program of
the Center for Cancer Research, NCI, National Institutes of Health.
NR 37
TC 8
Z9 8
U1 1
U2 16
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 1535-9476
EI 1535-9484
J9 MOL CELL PROTEOMICS
JI Mol. Cell. Proteomics
PD AUG
PY 2013
VL 12
IS 8
BP 2126
EP 2135
DI 10.1074/mcp.M113.028324
PG 10
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 277SH
UT WOS:000328839100008
PM 23637421
ER
PT J
AU Friedman, JA
Wise, SC
Hu, M
Gouveia, C
Vander Broek, R
Freudlsperger, C
Kannabiran, VR
Arun, P
Mitchell, JB
Chen, Z
Van Waes, C
AF Friedman, Jay A.
Wise, Stephanie C.
Hu, Michael
Gouveia, Chris
Vander Broek, Robert
Freudlsperger, Christian
Kannabiran, Vishnu R.
Arun, Pattatheyil
Mitchell, James B.
Chen, Zhong
Van Waes, Carter
TI HSP90 Inhibitor SNX5422/2112 Targets the Dysregulated Signal and
Transcription Factor Network and Malignant Phenotype of Head and Neck
Squamous Cell Carcinoma
SO TRANSLATIONAL ONCOLOGY
LA English
DT Article
ID EPIDERMAL-GROWTH-FACTOR; NF-KAPPA-B; SHOCK-PROTEIN 90; FACTOR-RECEPTOR;
HEAT-SHOCK-PROTEIN-90 INHIBITOR; CISPLATIN SENSITIVITY; THERAPEUTIC
TARGET; ANTITUMOR-ACTIVITY; PLUS CETUXIMAB; CANCER-CELLS
AB Heat shock protein 90 (HSP90) is a chaperone protein that stabilizes proteins involved in oncogenic and therapeutic resistance pathways of epithelial cancers, including head and neck squamous cell carcinomas (HNSCCs). Here, we characterized the molecular, cellular, and preclinical activity of HSP90 inhibitor SNX5422/2112 in HNSCC over-expressing HSP90. SNX2112 inhibited proliferation, induced G(2)/M block, and enhanced cytotoxicity, chemosensitivity, and radiosensitivity between 25 and 250 nM in vitro. SNX2112 showed combinatorial activity with paclitaxel in wild-type (wt) TP53-deficient and cisplatin in mutant (mt) TP53 HNSCC lines. SNX2112 decreased expression or phosphorylation of epidermal growth factor receptor (EGFR), c-MET, v-akt murine thymoma viral oncogene homolog 1 (AKT), extracellular signal-regulated kinases (ERK) 1 and 2, inhibitor kappa B kinase, and signal transducer and transcription factor 3 (STAT3), corresponding downstream nuclear factor kappa B, activator protein-1, and STAT3 reporter genes, and target oncogenes and angiogenic cytokines. Furthermore, SNX2112 enhanced re-expression of TP53 and targets p21WAF1 and PUMA, while TP53 inhibitor Pifithrin or siRNA attenuated the antiproliferative activity of SNX2112 in wtTP53 HNSCC in vitro. Prodrug SNX5422 similarly down-modulated key signal targets, enhanced TP53 expression and apoptosis, and inhibited proliferation, angiogenesis, and tumorigenesis in a wtTP53-deficient HNSCC xenograft model. Thus, HSP90 inhibitor SNX5422/2112 broadly modulates multiple key nodes within the dysregulated signaling network, with corresponding effects upon the malignant phenotype. Our data support investigation of SNX5422/2112 in combination with paclitaxel, cisplatin, and radiotherapy in HNSCC with different TP53 status.
C1 [Friedman, Jay A.; Wise, Stephanie C.; Hu, Michael; Gouveia, Chris; Vander Broek, Robert; Freudlsperger, Christian; Kannabiran, Vishnu R.; Arun, Pattatheyil; Chen, Zhong; Van Waes, Carter] Natl Inst Deafness & Other Commun Disorders, Tumor Biol Sect, Head & Neck Surg Branch, NIH, Bethesda, MD 20892 USA.
[Freudlsperger, Christian] Univ Hosp, Dept Oral & Maxillofacial Surg, Heidelberg, Germany.
[Mitchell, James B.] NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA.
RP Van Waes, C (reprint author), Natl Inst Deafness & Other Commun Disorders, NIH, CRC Rm 4-2732,Rm 5D55,10 Ctr Dr, Bethesda, MD 20892 USA.
EM chenz@nidcd.nih.gov; vanwaesc@nidcd.nih.gov
FU National Institute on Deafness and Other Communication Disorders (NIDCD)
[ZIA-DC-000073, ZIA-DC-000074]; Medical Research Training Program;
National Institutes of Health (NIH); Pfizer Inc
FX This work was supported by National Institute on Deafness and Other
Communication Disorders (NIDCD) intramural research program projects
ZIA-DC-000073 and 000074. S.C.W., M.H., C.G., R.V.B., and V.R.K. were
supported by the Medical Research Training Program, a public-private
partnership jointly sponsored by the National Institutes of Health (NIH)
and Pfizer Inc (through a grant to the Foundation for NIH from Pfizer
Inc). Synthetic HSP90 inhibitor SNX5422 (PF-04928473) and its oral
prodrug SNX2112 (PF-04929113) were provided to NIDCD and C.V.W. for
research under a Material Transfer Agreement with Pfizer Inc or Esanex
Inc. C.V.W. has no financial interests to disclose.
NR 63
TC 7
Z9 7
U1 1
U2 5
PU NEOPLASIA PRESS
PI ANN ARBOR
PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648
USA
SN 1944-7124
EI 1936-5233
J9 TRANSL ONCOL
JI Transl. Oncol.
PD AUG
PY 2013
VL 6
IS 4
BP 429
EP U141
DI 10.1593/tlo.13292
PG 20
WC Oncology
SC Oncology
GA 271AG
UT WOS:000328361500006
PM 23908686
ER
PT J
AU Iqbal, MB
Johns, M
Yu, SC
Hyde, GD
Gavins, FN
Blackshear, PJ
Mackman, N
Dean, JL
Boothby, M
Haskard, DO
AF Iqbal, M. B.
Johns, M.
Yu, S. C.
Hyde, G. D.
Gavins, F. N.
Blackshear, P. J.
Mackman, N.
Dean, J. L.
Boothby, M.
Haskard, D. O.
TI Poly(ADP-ribose) polymerase-14 interacts with tristetraprolin to
selectively regulate tissue factor mRNA stability: a novel role for
ADP-ribosylation in regulating mRNA turnover and thrombosis
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
CT Congress of the European-Society-of-Cardiology (ESC)
CY AUG 31-SEP 04, 2013
CL Amsterdam, NETHERLANDS
SP European Soc Cardiol
C1 [Iqbal, M. B.; Johns, M.; Yu, S. C.; Hyde, G. D.; Haskard, D. O.] Univ London Imperial Coll Sci Technol & Med, NHLI, London, England.
[Gavins, F. N.] Univ London Imperial Coll Sci Technol & Med, Fac Med, London, England.
[Blackshear, P. J.] NIEHS, Res Triangle Pk, NC 27709 USA.
[Mackman, N.] Univ N Carolina, Chapel Hill, NC USA.
[Dean, J. L.] Univ London Imperial Coll Sci Technol & Med, Kennedy Inst Rheumatol, London, England.
[Boothby, M.] Vanderbilt Univ, Nashville, TN 37235 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
EI 1522-9645
J9 EUR HEART J
JI Eur. Heart J.
PD AUG
PY 2013
VL 34
SU 1
BP 178
EP 179
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 262OH
UT WOS:000327744601096
ER
PT J
AU Grivel, JC
Ivanova, OI
Nikitskaya, EA
Pinegina, NV
Lebedeva, AM
Shpektor, AV
Vasilieva, E
Margolis, LB
AF Grivel, J. C.
Ivanova, O. I.
Nikitskaya, E. A.
Pinegina, N. V.
Lebedeva, A. M.
Shpektor, A. V.
Vasilieva, E.
Margolis, L. B.
TI Activation of T-lymphocytes and herpes viruses in atherosclerotic
plaques
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
CT Congress of the European-Society-of-Cardiology (ESC)
CY AUG 31-SEP 04, 2013
CL Amsterdam, NETHERLANDS
SP European Soc Cardiol
C1 [Grivel, J. C.; Margolis, L. B.] NIH, Washington, DC USA.
[Ivanova, O. I.; Nikitskaya, E. A.; Pinegina, N. V.; Lebedeva, A. M.; Shpektor, A. V.; Vasilieva, E.] Moscow State Univ Med & Dent, Moscow, Russia.
RI Shpektor, Alexander/B-1083-2016; Vasilieva, Elena/B-2137-2016; Ivanova,
Oxana/L-8578-2016
OI Ivanova, Oxana/0000-0002-8477-9706
NR 0
TC 0
Z9 0
U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
EI 1522-9645
J9 EUR HEART J
JI Eur. Heart J.
PD AUG
PY 2013
VL 34
SU 1
BP 442
EP 442
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 262OH
UT WOS:000327744602536
ER
PT J
AU Grivel, JC
Nikitskaya, E
Ivanova, O
Ryazankina, N
Pinegina, N
Lebedeva, A
Shpektor, A
Margolis, L
Vasilieva, E
AF Grivel, J. C.
Nikitskaya, E.
Ivanova, O.
Ryazankina, N.
Pinegina, N.
Lebedeva, A.
Shpektor, A.
Margolis, L.
Vasilieva, E.
TI Comparison amount of human herpes viruses DNA in vessels from different
group of patients
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
CT Congress of the European-Society-of-Cardiology (ESC)
CY AUG 31-SEP 04, 2013
CL Amsterdam, NETHERLANDS
SP European Soc Cardiol
C1 [Grivel, J. C.; Margolis, L.] NIH, Washington, DC USA.
[Nikitskaya, E.; Ivanova, O.; Ryazankina, N.; Pinegina, N.; Lebedeva, A.; Shpektor, A.; Vasilieva, E.] Moscow State Univ Med & Dent, Moscow, Russia.
RI Shpektor, Alexander/B-1083-2016; Vasilieva, Elena/B-2137-2016
NR 0
TC 0
Z9 0
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
EI 1522-9645
J9 EUR HEART J
JI Eur. Heart J.
PD AUG
PY 2013
VL 34
SU 1
BP 445
EP 445
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 262OH
UT WOS:000327744602546
ER
PT J
AU Redheuil, A
Wu, C
Yan, RT
Bertoni, AG
Hundley, GW
Duprez, DA
Jacobs, DR
Daniels, LB
Bluemke, DA
Lima, JAC
AF Redheuil, A.
Wu, C.
Yan, R. T.
Bertoni, A. G.
Hundley, G. W.
Duprez, D. A.
Jacobs, D. R.
Daniels, L. B.
Bluemke, D. A.
Lima, J. A. C.
CA Multi Ethnic Study Atherosclerosis
TI Proximal aortic distensibility is an independent predictor of all-cause
mortality and incident cardiovascular events in the multi-ethnic study
of atherosclerosis
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
CT Congress of the European-Society-of-Cardiology (ESC)
CY AUG 31-SEP 04, 2013
CL Amsterdam, NETHERLANDS
SP European Soc Cardiol
C1 [Redheuil, A.] Univ Paris 06, INSERM, U678, Paris, France.
[Wu, C.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Yan, R. T.] Toronto Gen Hosp, Toronto, ON, Canada.
[Bertoni, A. G.; Hundley, G. W.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA.
[Duprez, D. A.; Jacobs, D. R.] Univ Minnesota, Minneapolis, MN USA.
[Daniels, L. B.] Univ Calif San Diego, La Jolla, CA 92093 USA.
[Bluemke, D. A.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Lima, J. A. C.] Johns Hopkins Univ, Div Cardiol, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
EI 1522-9645
J9 EUR HEART J
JI Eur. Heart J.
PD AUG
PY 2013
VL 34
SU 1
BP 490
EP 490
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 262OH
UT WOS:000327744603037
ER
PT J
AU Gardarsdottir, M
Sigurdsson, S
Aspelund, T
Launer, LJ
Gudnason, V
Arnar, DO
AF Gardarsdottir, M.
Sigurdsson, S.
Aspelund, T.
Launer, L. J.
Gudnason, V.
Arnar, D. O.
TI Is atrial fibrillation associated with a decrease in total brain
perfusion?
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
CT Congress of the European-Society-of-Cardiology (ESC)
CY AUG 31-SEP 04, 2013
CL Amsterdam, NETHERLANDS
SP European Soc Cardiol
C1 [Gardarsdottir, M.; Arnar, D. O.] Natl Univ Hosp Iceland, Landspitali, Reykjavik, Iceland.
[Sigurdsson, S.; Aspelund, T.; Gudnason, V.] Iceland Heart Assoc, Kopavogur, Iceland.
[Launer, L. J.] NIH, Bethesda, MD 20892 USA.
RI Aspelund, Thor/C-5983-2008; Gudnason, Vilmundur/K-6885-2015
OI Aspelund, Thor/0000-0002-7998-5433; Gudnason,
Vilmundur/0000-0001-5696-0084
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
EI 1522-9645
J9 EUR HEART J
JI Eur. Heart J.
PD AUG
PY 2013
VL 34
SU 1
BP 741
EP 742
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 262OH
UT WOS:000327744604453
ER
PT J
AU Deseive, SDC
Menges, AL
Leipsic, J
Korosoglou, G
Mirsadraee, S
Martuscelli, E
Chen, M
Martinoff, S
Hadamitzky, M
Hausleiter, J
AF Deseive, S. D. C.
Menges, A. L.
Leipsic, J.
Korosoglou, G.
Mirsadraee, S.
Martuscelli, E.
Chen, M.
Martinoff, S.
Hadamitzky, M.
Hausleiter, J.
TI Prospective randomized trial on radiation dose estimates of CT
angiography in patients applying Iterative image reconstruction
techniques - results of the PROTECTION V study
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
CT Congress of the European-Society-of-Cardiology (ESC)
CY AUG 31-SEP 04, 2013
CL Amsterdam, NETHERLANDS
SP European Soc Cardiol
C1 [Deseive, S. D. C.; Menges, A. L.] German Heart Ctr, Clin Heart & Circulatory Dis, Munich, Germany.
[Leipsic, J.] St Pauls Hosp, Vancouver, BC V6Z 1Y6, Canada.
[Korosoglou, G.] Univ Heidelberg Hosp, Dept Cardiol, Heidelberg, Germany.
[Mirsadraee, S.] Univ Edinburgh, Clin Res Imaging Ctr, Edinburgh, Midlothian, Scotland.
[Martuscelli, E.] Univ Rome, Polyclin Tor Vergata, Dept Internal Med, Rome, Italy.
[Chen, M.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Martinoff, S.; Hadamitzky, M.] TUM, German Heart Ctr, Dept Radiol & Nucl Med, Munich, Germany.
[Hausleiter, J.] Univ Munich, Dept Cardiol, Munich, Germany.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
EI 1522-9645
J9 EUR HEART J
JI Eur. Heart J.
PD AUG
PY 2013
VL 34
SU 1
BP 839
EP 839
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 262OH
UT WOS:000327744605132
ER
PT J
AU Claessen, BEPM
Syros, G
Mehran, R
Sanidas, AE
Chantziara, V
Apostolidou, I
Weisz, G
Rabbani, L
Hooper, C
Dangas, GD
AF Claessen, B. E. P. M.
Syros, G.
Mehran, R.
Sanidas, A. E.
Chantziara, V.
Apostolidou, I.
Weisz, G.
Rabbani, L.
Hooper, C.
Dangas, G. D.
TI Impact of multiple polymorphisms on clinical outcomes after percutaneous
coronary intervention
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
CT Congress of the European-Society-of-Cardiology (ESC)
CY AUG 31-SEP 04, 2013
CL Amsterdam, NETHERLANDS
SP European Soc Cardiol
C1 [Claessen, B. E. P. M.] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands.
[Syros, G.] Tufts Med Ctr, Boston, MA USA.
[Mehran, R.; Dangas, G. D.] Mt Sinai Med Ctr, New York, NY 10029 USA.
[Mehran, R.; Sanidas, A. E.; Chantziara, V.; Apostolidou, I.; Weisz, G.; Rabbani, L.; Dangas, G. D.] Cardiovasc Res Fdn, New York, NY USA.
[Sanidas, A. E.; Chantziara, V.; Apostolidou, I.; Weisz, G.; Rabbani, L.] Columbia Univ, Med Ctr, New York, NY USA.
[Hooper, C.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
EI 1522-9645
J9 EUR HEART J
JI Eur. Heart J.
PD AUG
PY 2013
VL 34
SU 1
BP 872
EP 872
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 262OH
UT WOS:000327744605252
ER
PT J
AU Jiang, BM
Wang, YH
Glass, RI
AF Jiang, Baoming
Wang, Yuhuan
Glass, Roger I.
TI Does a monovalent inactivated human rotavirus vaccine induce heterotypic
immunity? Evidence from animal studies
SO HUMAN VACCINES & IMMUNOTHERAPEUTICS
LA English
DT Article
DE rotavirus; IRV; CDC-9; heat inactivation; heterotypic protection
ID INFANTS; INFECTION; MICE
AB There is substantial evidence for broad cross-reactive immunity and heterotypic protection among human rotavirus strains in children with natural infection or with monovalent Rotarix vaccination. In this commentary, we addressed this same topic by testing sera of guinea pigs and gnotobiotic piglets that were intramuscularly immunized with an inactivated human rotavirus vaccine and also demonstrated a broad cross-protective immunity among human rotavirus strains. Our findings from a single human strain in animal studies bode well for a low cost and efficacious inactivated vaccine to protect children against rotavirus disease throughout the world.
C1 [Jiang, Baoming; Wang, Yuhuan] Ctr Dis Control & Prevent, Div Viral Dis, Atlanta, GA 30329 USA.
[Glass, Roger I.] NIH, Forgaty Int Ctr, Bethesda, MD 20892 USA.
RP Jiang, BM (reprint author), Ctr Dis Control & Prevent, Div Viral Dis, Atlanta, GA 30329 USA.
EM bxj4@cdc.gov
NR 18
TC 7
Z9 8
U1 0
U2 4
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 2164-5515
EI 2164-554X
J9 HUM VACC IMMUNOTHER
JI Human Vaccines Immunother.
PD AUG 1
PY 2013
VL 9
IS 8
BP 1634
EP 1637
DI 10.4161/hv.24958
PG 4
WC Biotechnology & Applied Microbiology; Immunology
SC Biotechnology & Applied Microbiology; Immunology
GA 259SY
UT WOS:000327547800006
PM 23744507
ER
PT J
AU Fu, ZM
Wang, MY
Everett, A
Lakatta, E
Van Eyk, J
AF Fu, Zongming
Wang, Mingyi
Everett, Allen
Lakatta, Edward
Van Eyk, Jennifer
TI Can proteomics yield insight into aging aorta?
SO PROTEOMICS CLINICAL APPLICATIONS
LA English
DT Review
DE Aging aorta; Biomarker; Milk fat globule-EGF factor 8; Therapeutic
target
ID SMOOTH-MUSCLE-CELLS; SUBCLINICAL ARTERIAL-DISEASE; RENIN-ANGIOTENSIN
SYSTEM; CYSTEINE-RICH PROTEIN-2; RAT SKELETAL-MUSCLE;
GROWTH-FACTOR-BETA; CARDIOVASCULAR-DISEASE; CORONARY ATHEROSCLEROSIS;
MASS-SPECTROMETRY; TGF-BETA
AB The aging aorta exhibits structural and physiological changes that are reflected in the proteome of its component cells types. The advance in proteomic technologies has made it possible to analyze the quantity of proteins associated with the natural history of aortic aging. These alterations reflect the molecular and cellular mechanisms of aging and could provide an opportunity to predict vascular health. This paper focuses on whether discoveries stemming from the application of proteomic approaches of the intact aging aorta or vascular smooth muscle cells can provide useful insights. Although there have been limited studies to date, a number of interesting proteins have been identified that are closely associated with aging in the rat aorta. Such proteins, including milk fat globule-EGF factor 8, matrix metalloproteinase type-2, and vitronectin, could be used as indicators of vascular health, or even explored as therapeutic targets for aging-related vascular diseases.
C1 [Fu, Zongming; Everett, Allen] Johns Hopkins Univ, Dept Pediat, Baltimore, MD 21224 USA.
[Wang, Mingyi; Lakatta, Edward] NIA, Lab Cardiovasc Sci, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Van Eyk, Jennifer] Johns Hopkins Univ, Dept Med, Baltimore, MD 21224 USA.
[Van Eyk, Jennifer] Johns Hopkins Univ, Dept Biol Chem, Baltimore, MD 21224 USA.
[Van Eyk, Jennifer] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21224 USA.
RP Van Eyk, J (reprint author), Johns Hopkins Univ, Dept Med, Baltimore, MD 21224 USA.
EM jvaneyk1@jhmi.edu
FU Intramural Research Program of the National Institute on Aging;
[NHLBI-HV-10-05 (2)]; [PO1 HL10026]; [1R01HL111362-01A]
FX This research was supported by NHLBI-HV-10-05 (2) (J.V.E.), PO1 HL10026
(J.V.E.) and 1R01HL111362-01A (J.V.E., D.H.), and the Intramural
Research Program of the National Institute on Aging.
NR 159
TC 2
Z9 2
U1 0
U2 14
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA POSTFACH 101161, 69451 WEINHEIM, GERMANY
SN 1862-8346
EI 1862-8354
J9 PROTEOM CLIN APPL
JI Proteom. Clin. Appl.
PD AUG
PY 2013
VL 7
IS 7-8
SI SI
BP 477
EP 489
DI 10.1002/prca.201200138
PG 13
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 263FQ
UT WOS:000327792800003
PM 23788441
ER
PT J
AU Abraham, TM
Fox, CS
AF Abraham, Tobin M.
Fox, Caroline S.
TI Implications of Rising Prediabetes Prevalence
SO DIABETES CARE
LA English
DT Editorial Material
ID IMPAIRED GLUCOSE-TOLERANCE; DIABETES PREVENTION PROGRAM; FASTING
GLUCOSE; LIFE-STYLE; CARDIOVASCULAR-DISEASE; A1C ASSAY; RISK; METFORMIN;
MELLITUS; HEMOGLOBIN
C1 [Abraham, Tobin M.; Fox, Caroline S.] Brigham & Womens Hosp, Dept Endocrinol Hypertens & Diabet, Boston, MA 02115 USA.
[Abraham, Tobin M.; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA.
[Abraham, Tobin M.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Fox, Caroline S.] NHLBI, Bethesda, MD 20892 USA.
RP Fox, CS (reprint author), Brigham & Womens Hosp, Dept Endocrinol Hypertens & Diabet, 75 Francis St, Boston, MA 02115 USA.
EM foxca@nhlbi.nih.gov
NR 25
TC 10
Z9 10
U1 0
U2 1
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD AUG
PY 2013
VL 36
IS 8
BP 2139
EP 2141
DI 10.2337/dc13-0792
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 255PP
UT WOS:000327252600020
PM 23881964
ER
PT J
AU Rother, KI
Brown, RJ
AF Rother, Kristina I.
Brown, Rebecca J.
TI Novel Forms of Lipodystrophy Why should we care?
SO DIABETES CARE
LA English
DT Editorial Material
ID JOINT CONTRACTURES; MICROCYTIC ANEMIA; FAT; ATROPHY
C1 [Rother, Kristina I.; Brown, Rebecca J.] Natl Inst Diabet & Digest & Kidney Dis, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA.
RP Rother, KI (reprint author), Natl Inst Diabet & Digest & Kidney Dis, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA.
EM kristina.rother@nih.gov
FU Intramural NIH HHS
NR 16
TC 6
Z9 8
U1 0
U2 1
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD AUG
PY 2013
VL 36
IS 8
BP 2142
EP 2145
DI 10.2337/dc13-0561
PG 4
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 255PP
UT WOS:000327252600021
PM 23881965
ER
PT J
AU Nathan, DM
Buse, JB
Kahn, SE
Krause-Steinrauf, H
Larkin, ME
Staten, M
Wexler, D
Lachin, JM
AF Nathan, David M.
Buse, John B.
Kahn, Steven E.
Krause-Steinrauf, Heidi
Larkin, Mary E.
Staten, Myrlene
Wexler, Deborah
Lachin, John M.
CA GRADE Study Res Grp
TI Rationale and Design of the Glycemia Reduction Approaches in Diabetes: A
Comparative Effectiveness Study (GRADE)
SO DIABETES CARE
LA English
DT Article
ID IMPAIRED GLUCOSE-TOLERANCE; CARDIOVASCULAR-DISEASE; GLYBURIDE
MONOTHERAPY; LIFE-STYLE; FOLLOW-UP; MELLITUS; METFORMIN; HYPERGLYCEMIA;
ASSOCIATION; PREVENTION
AB OBJECTIVEThe epidemic of type 2 diabetes (T2DM) threatens to become the major public health problem of this century. However, a comprehensive comparison of the long-term effects of medications to treat T2DM has not been conducted. GRADE, a pragmatic, unmasked clinical trial, aims to compare commonly used diabetes medications, when combined with metformin, on glycemia-lowering effectiveness and patient-centered outcomes.RESEARCH DESIGN AND METHODSGRADE was designed with support from a U34 planning grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The consensus protocol was approved by NIDDK and the GRADE Research Group. Eligibility criteria for the 5,000 metformin-treated subjects include <5 years' diabetes duration, 30 years of age at time of diagnosis, and baseline hemoglobin A(1c) (A1C) of 6.8-8.5% (51-69 mmol/mol). Medications representing four classes (sulfonylureas, dipeptidyl peptidase 4 inhibitors, glucagon-like peptide 1 receptor agonists, and insulin) will be randomly assigned and added to metformin (minimum-maximum 1,000-2,000 mg/day). The primary metabolic outcome is the time to primary failure defined as an A1C 7% (53 mmol/mol), subsequently confirmed, over an anticipated mean observation period of 4.8 years (range 4-7 years). Other long-term metabolic outcomes include the need for the addition of basal insulin after a confirmed A1C >7.5% (58 mmol/mol) and, ultimately, the need to implement an intensive basal/bolus insulin regimen. The four drugs will also be compared with respect to selected microvascular complications, cardiovascular disease risk factors, adverse effects, tolerability, quality of life, and cost-effectiveness.CONCLUSIONSGRADE will compare the long-term effectiveness of major glycemia-lowering medications and provide guidance to clinicians about the most appropriate medications to treat T2DM. GRADE begins recruitment at 37 centers in the U.S. in 2013.
C1 [Nathan, David M.; Larkin, Mary E.; Wexler, Deborah] Massachusetts Gen Hosp, Diabet Res Ctr, Boston, MA 02114 USA.
[Nathan, David M.; Larkin, Mary E.; Wexler, Deborah] Harvard Univ, Sch Med, Boston, MA USA.
[Buse, John B.] Univ N Carolina, Dept Med, Div Endocrinol, Chapel Hill, NC USA.
[Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA.
[Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA.
[Krause-Steinrauf, Heidi; Lachin, John M.] George Washington Univ, Ctr Biostat, Rockville, MD 20852 USA.
[Staten, Myrlene] Natl Inst Diabet & Digest & Kidney Dis, Bethesda, MD USA.
RP Krause-Steinrauf, H (reprint author), George Washington Univ, Ctr Biostat, Rockville, MD 20852 USA.
EM heidi@bsc.gwu.edu
OI Lachin, John/0000-0001-9838-2841; Kahn, Steven/0000-0001-7307-9002
FU NIDDK, NIH [5U34-DK-088043-02]; American Diabetes Association; Abbott;
Amylin; Andromeda; AstraZeneca; Bayhill Therapeutics; BD Research
Laboratories; Boehringer Ingelheim; Bristol-Myers Squibb; Catabasis;
Cebix; Diartis, Elcelyx; Eli Lilly; Exsulin; Genentech; GI Dynamics;
GlaxoSmithKline; Halozyme; Hoffman-La Roche; Johnson Johnson;
LipoScience; Medtronic; Merck; Metabolic Solutions Development Company;
Metabolon; Novan; Novella; Novartis; Novo Nordisk; Orexigen; Osiris;
Pfizer; Rhythm; Sanofi; Spherix; Takeda; Tolerex; TransPharma; Veritas;
Verva; [1U01-DK-098246-01]
FX The planning of GRADE was supported by a U34 planning grant from the
NIDDK, NIH (5U34-DK-088043-02). The American Diabetes Association
provided funds for the initial planning meeting for developing the U34
proposal. GRADE is supported by a U01 grant (1U01-DK-098246-01).
Educational materials have been provided by the National Diabetes
Education Program. Material support in the form of donated medications
and supplies has been provided by BD, Bristol-Myers Squibb, Merck, Novo
Nordisk, Roche Diagnostics, and Sanofi.; J.B.B.'s employer (the
University of North Carolina) has received payments for his work as a
consultant or investigator from Abbott, Amylin, Andromeda, AstraZeneca,
Bayhill Therapeutics, BD Research Laboratories, Boehringer Ingelheim,
Bristol-Myers Squibb, Catabasis, Cebix, Diartis, Elcelyx, Eli Lilly,
Exsulin, Genentech, GI Dynamics, GlaxoSmithKline, Halozyme, Hoffman-La
Roche, Johnson & Johnson, LipoScience, Medtronic, Merck, Metabolic
Solutions Development Company, Metabolon, Novan, Novella, Novartis, Novo
Nordisk, Orexigen, Osiris, Pfizer, Rhythm, Sanofi, Spherix, Takeda,
Tolerex, TransPharma, Veritas, and Verva. S.E.K. has received honoraria
for consulting from Boehringer Ingelheim, Bristol-Myers Squibb, Eli
Lilly, GlaxoSmithKline, Intarcia Therapeutics, Janssen, Merck, Novo
Nordisk, and Receptos and honoraria for speaking from Boehringer
Ingelheim and Merck. J.M.L. has received honoraria for consulting from
Merck, Boehringer Ingelheim, Eli Lilly, Novartis, and Janssen. No other
potential conflicts of interest relevant to this article were reported.
NR 40
TC 61
Z9 61
U1 1
U2 5
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD AUG
PY 2013
VL 36
IS 8
BP 2254
EP 2261
DI 10.2337/dc13-0356
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 255PP
UT WOS:000327252600038
PM 23690531
ER
PT J
AU Casagrande, SS
Fradkin, JE
Saydah, SH
Rust, KF
Cowie, CC
AF Casagrande, Sarah Stark
Fradkin, Judith E.
Saydah, Sharon H.
Rust, Keith F.
Cowie, Catherine C.
TI The Prevalence of Meeting A1C, Blood Pressure, and LDL Goals Among
People With Diabetes, 1988-2010
SO DIABETES CARE
LA English
DT Article
ID UNITED-STATES; ADULTS; CHOLESTEROL; DISEASE; TRENDS; OVERWEIGHT; RACE
AB OBJECTIVETo determine the prevalence of people with diabetes who meet hemoglobin A(1c) (A1C), blood pressure (BP), and LDL cholesterol (ABC) recommendations and their current statin use, factors associated with goal achievement, and changes in the proportion achieving goals between 1988 and 2010.RESEARCH DESIGN AND METHODSData were cross-sectional from the National Health and Nutrition Examination Surveys (NHANES) from 1988-1994, 1999-2002, 2003-2006, and 2007-2010. Participants were 4,926 adults aged 20 years who self-reported a previous diagnosis of diabetes and completed the household interview and physical examination (n = 1,558 for valid LDL levels). Main outcome measures were A1C, BP, and LDL cholesterol, in accordance with the American Diabetes Association recommendations, and current use of statins.RESULTSIn 2007-2010, 52.5% of people with diabetes achieved A1C <7.0% (<53 mmol/mol), 51.1% achieved BP <130/80 mmHg, 56.2% achieved LDL <100 mg/dL, and 18.8% achieved all three ABCs. These levels of control were significant improvements from 1988 to 1994 (all P < 0.05). Statin use significantly increased between 1988-1994 (4.2%) and 2007-2010 (51.4%, P < 0.01). Compared with non-Hispanic whites, Mexican Americans were less likely to meet A1C and LDL goals (P < 0.03), and non-Hispanic blacks were less likely to meet BP and LDL goals (P < 0.02). Compared with non-Hispanic blacks, Mexican Americans were less likely to meet A1C goals (P < 0.01). Younger individuals were less likely to meet A1C and LDL goals.CONCLUSIONSDespite significant improvement during the past decade, achieving the ABC goals remains suboptimal among adults with diabetes, particularly in some minority groups. Substantial opportunity exists to further improve diabetes control and, thus, to reduce diabetes-related morbidity and mortality.
C1 [Casagrande, Sarah Stark] Social & Sci Syst Inc, Silver Spring, MD 20910 USA.
[Fradkin, Judith E.; Cowie, Catherine C.] Natl Inst Diabet & Digest & Kidney Dis, Div Diabet Endocrinol & Metab Dis, Bethesda, MD USA.
[Saydah, Sharon H.] US Ctr Dis Control & Prevent, Div Diabet Translat, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA.
[Rust, Keith F.] WESTAT Corp, Rockville, MD 20850 USA.
RP Casagrande, SS (reprint author), Social & Sci Syst Inc, Silver Spring, MD 20910 USA.
EM scasagrande@s-3.com
FU National Institute of Diabetes and Digestive and Kidney Diseases
[GS-10F-0381L]
FX This work was financially supported by the National Institute of
Diabetes and Digestive and Kidney Diseases (GS-10F-0381L). The findings
and conclusions in this report are those of the authors and do not
necessarily represent the official position of the National Institute of
Diabetes and Digestive and Kidney Diseases or the Centers for Disease
Control and Prevention/the Agency for Toxic Substances and Disease
Registry.
NR 24
TC 93
Z9 95
U1 1
U2 8
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD AUG
PY 2013
VL 36
IS 8
BP 2271
EP 2279
DI 10.2337/dc12-2258
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 255PP
UT WOS:000327252600041
ER
PT J
AU Bullard, KM
Saydah, SH
Imperatore, G
Cowie, CC
Gregg, EW
Geiss, LS
Cheng, YLJ
Rolka, DB
Williams, DE
Caspersen, CJ
AF Bullard, Kai McKeever
Saydah, Sharon H.
Imperatore, Giuseppina
Cowie, Catherine C.
Gregg, Edward W.
Geiss, Linda S.
Cheng, Yiling J.
Rolka, Deborah B.
Williams, Desmond E.
Caspersen, Carl J.
TI Secular Changes in US Prediabetes Prevalence Defined by Hemoglobin A(1c)
and Fasting Plasma Glucose National Health and Nutrition Examination
Surveys, 1999-2010
SO DIABETES CARE
LA English
DT Article
ID DIABETES PREVENTION PROGRAM; LIFE-STYLE INTERVENTION;
CARDIOVASCULAR-DISEASE; COMMUNITY; DIAGNOSIS; MELLITUS; REDUCTION;
TOLERANCE; ADULTS; RISK
AB OBJECTIVEUsing a nationally representative sample of the civilian noninstitutionalized U.S. population, we estimated prediabetes prevalence and its changes during 1999-2010.RESEARCH DESIGN AND METHODSData were from 19,182 nonpregnant individuals aged 12 years who participated in the 1999-2010 National Health and Nutrition Examination Surveys. We defined prediabetes as hemoglobin A(1c) (A1C) 5.7 to <6.5% (39 to <48 mmol/mol, A1C5.7) or fasting plasma glucose (FPG) 100 to <126 mg/dL (impaired fasting glucose [IFG]). We estimated the prevalence of prediabetes, A1C5.7, and IFG for 1999-2002, 2003-2006, and 2007-2010. We calculated estimates age-standardized to the 2000 U.S. census population and used logistic regression to compute estimates adjusted for age, sex, race/ethnicity, poverty-to-income ratio, and BMI. Participants with self-reported diabetes, A1C 6.5% (48 mmol/mol), or FPG 126 mg/dL were included.RESULTSAmong those aged 12 years, age-adjusted prediabetes prevalence increased from 27.4% (95% CI 25.1-29.7) in 1999-2002 to 34.1% (32.5-35.8) in 2007-2010. Among adults aged 18 years, the prevalence increased from 29.2% (26.8-31.8) to 36.2% (34.5-38.0). As single measures among individuals aged 12 years, A1C5.7 prevalence increased from 9.5% (8.4-10.8) to 17.8% (16.6-19.0), a relative increase of 87%, whereas IFG remained stable. These prevalence changes were similar among the total population, across subgroups, and after controlling for covariates.CONCLUSIONSDuring 1999-2010, U.S. prediabetes prevalence increased because of increases in A1C5.7. Continuous monitoring of prediabetes is needed to identify, quantify, and characterize the population of high-risk individuals targeted for ongoing diabetes primary prevention efforts.
C1 [Bullard, Kai McKeever; Saydah, Sharon H.; Imperatore, Giuseppina; Gregg, Edward W.; Geiss, Linda S.; Cheng, Yiling J.; Rolka, Deborah B.; Williams, Desmond E.; Caspersen, Carl J.] Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA 30333 USA.
[Cowie, Catherine C.] Natl Inst Diabet & Digest & Kidney Dis, NIH, Bethesda, MD USA.
RP Bullard, KM (reprint author), Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA 30333 USA.
EM hjo1@cdc.gov
NR 35
TC 70
Z9 70
U1 0
U2 3
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD AUG
PY 2013
VL 36
IS 8
BP 2286
EP 2293
DI 10.2337/dc12-2563
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 255PP
UT WOS:000327252600043
PM 23603918
ER
PT J
AU Turkbey, EB
Redheuil, A
Backlund, JYC
Small, AC
Cleary, PA
Lachin, JM
Lima, JAC
Bluemke, DA
AF Turkbey, Evrim B.
Redheuil, Alban
Backlund, Jye-Yu C.
Small, Alexander C.
Cleary, Patricia A.
Lachin, John M.
Lima, Joao A. C.
Bluemke, David A.
CA Diabet Control Complications Trial
TI Aortic Distensibility in Type 1 Diabetes
SO DIABETES CARE
LA English
DT Article
ID EURODIAB PROSPECTIVE COMPLICATIONS; CHRONIC KIDNEY-DISEASE; PULSE-WAVE
VELOCITY; ARTERIAL STIFFNESS; CARDIOVASCULAR-DISEASE; ENDOTHELIAL
DYSFUNCTION; CLINICAL-APPLICATIONS; AUTONOMIC NEUROPATHY; WALL
PROPERTIES; RISK-FACTORS
AB OBJECTIVETo evaluate the relationship between long-term glycemia, traditional cardiovascular disease (CVD) risk factors, and ascending aortic stiffness in type 1 diabetes.RESEARCH DESIGN AND METHODSEight hundred seventy-nine subjects in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study were evaluated. The stiffness/distensibility of the ascending thoracic aorta (AA) was measured with magnetic resonance imaging. Associations of AA distensibility and CVD risk factors, mean HbA(1c), and cardiovascular complications including macroalbuminuria were assessed using multivariate linear regression models.RESULTSThe mean age of the subjects was 50 7 years (47% women, mean diabetes duration of 28 years). Over 22 years of follow-up, 27% of participants had cardiovascular complications. After adjusting for gender and cohort, AA distensibility was lower with increasing age, mean systolic blood pressure, LDL, and HbA(1c) measured over an average of 22 years (-26.3% per 10 years, -11.0% per 10 mmHg SBP, -1.8% per 10 mg/dL of LDL, and -9.3% per unit mean HbA(1c) [%], respectively). Patients with macroalbuminuria had 25% lower AA distensibility compared with those without (P < 0.0001). Lower AA distensibility also was associated with greater ratio of left ventricular mass to volume (-3.4% per 0.1 g/mL; P < 0.0001).CONCLUSIONSOur findings indicate strong adverse effects of hypertension, chronic hyperglycemia and macroalbuminuria on AA stiffness in type 1 diabetes in the DCCT/EDIC cohort.
C1 [Turkbey, Evrim B.; Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, NIH, Ctr Clin, Bethesda, MD USA.
[Redheuil, Alban] Univ Paris 06, Grp Hosp Pitie Salpetriere, Dept Cardiovasc Radiol, Paris, France.
[Redheuil, Alban] INSERM, Biomed Imaging Lab, U678, Paris, France.
[Backlund, Jye-Yu C.; Cleary, Patricia A.; Lachin, John M.] George Washington Univ, Ctr Biostat, Rockville, MD USA.
[Small, Alexander C.] Mt Sinai Sch Med, New York, NY USA.
[Lima, Joao A. C.] Johns Hopkins Univ, Dept Cardiol & Radiol, Baltimore, MD USA.
RP Bluemke, DA (reprint author), Natl Inst Biomed Imaging & Bioengn, NIH, Ctr Clin, Bethesda, MD USA.
EM bluemked@nih.gov
OI Lachin, John/0000-0001-9838-2841; Bluemke, David/0000-0002-8323-8086
FU National Institute of Diabetes and Digestive and Kidney Diseases,
National Eye Institute, National Institute of Neurological Disorders and
Stroke; General Clinical Research Centers Program; Clinical and
Translation Science Centers Program, National Center for Research
Resources; Genentech; National Institute of Diabetes and Digestive and
Kidney Diseases; intramural National Institutes of Health research
program
FX The DCCT/EDIC project is supported by contracts with the Division of
Diabetes, Endocrinology, and Metabolic Diseases of the National
Institute of Diabetes and Digestive and Kidney Diseases, National Eye
Institute, National Institute of Neurological Disorders and Stroke, the
General Clinical Research Centers Program and the Clinical and
Translation Science Centers Program, National Center for Research
Resources, and by Genentech through a Cooperative Research and
Development Agreement with the National Institute of Diabetes and
Digestive and Kidney Diseases. The study is also supported in part by
the intramural National Institutes of Health research program.
NR 43
TC 6
Z9 6
U1 0
U2 2
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD AUG
PY 2013
VL 36
IS 8
BP 2380
EP 2387
DI 10.2337/dc12-0393
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 255PP
UT WOS:000327252600056
PM 23474588
ER
PT J
AU Muniyappa, R
Sable, S
Ouwerkerk, R
Mari, A
Gharib, AM
Walter, M
Courville, A
Hall, G
Chen, KY
Volkow, ND
Kunos, G
Huestis, MA
Skarulis, MC
AF Muniyappa, Ranganath
Sable, Sara
Ouwerkerk, Ronald
Mari, Andrea
Gharib, Ahmed M.
Walter, Mary
Courville, Amber
Hall, Gail
Chen, Kong Y.
Volkow, Nora D.
Kunos, George
Huestis, Marilyn A.
Skarulis, Monica C.
TI Metabolic Effects of Chronic Cannabis Smoking
SO DIABETES CARE
LA English
DT Article
ID ASSESSING INSULIN SENSITIVITY; GLUCOSE-TOLERANCE TEST; SUBCUTANEOUS
ADIPOSE-TISSUE; ENDOCANNABINOID SYSTEM; RISK-FACTORS; CARDIOVASCULAR
RISK; OBESE MEN; RESISTANCE; MARIJUANA; MARIHUANA
AB OBJECTIVEWe examined if chronic cannabis smoking is associated with hepatic steatosis, insulin resistance, reduced -cell function, or dyslipidemia in healthy individuals.RESEARCH DESIGN AND METHODSIn a cross-sectional, case-control study, we studied cannabis smokers (n = 30; women, 12; men, 18; 27 8 years) and control subjects (n = 30) matched for age, sex, ethnicity, and BMI (27 6). Abdominal fat depots and intrahepatic fat content were quantified by magnetic resonance imaging and proton magnetic resonance spectroscopy, respectively. Insulin-sensitivity indices and various aspects of -cell function were derived from oral glucose tolerance tests (OGTT).RESULTSSelf-reported cannabis use was: 9.5 (2-38) years; joints/day: 6 (3-30) [median (range)]. Carbohydrate intake and percent calories from carbohydrates, but not total energy intake, were significantly higher in cannabis smokers. There were no group differences in percent total body fat, or hepatic fat, but cannabis smokers had a higher percent abdominal visceral fat (18 +/- 9 vs. 12 +/- 5%; P = 0.004). Cannabis smokers had lower plasma HDL cholesterol (49 +/- 14 vs. 55 +/- 13 mg/dL; P = 0.02), but fasting levels of glucose, insulin, total cholesterol, LDL cholesterol, triglycerides, or free fatty acids (FFA) were not different. Adipocyte insulin resistance index and percent FFA suppression during an OGTT was lower (P < 0.05) in cannabis smokers. However, oral glucose insulin sensitivity index, measures of -cell function, or incretin concentrations did not differ between the groups.CONCLUSIONSChronic cannabis smoking was associated with visceral adiposity and adipose tissue insulin resistance but not with hepatic steatosis, insulin insensitivity, impaired pancreatic -cell function, or glucose intolerance.
C1 [Muniyappa, Ranganath; Sable, Sara; Hall, Gail; Chen, Kong Y.; Skarulis, Monica C.] Natl Inst Diabet & Digest & Kidney Dis, Diabet Endocrinol & Obes Branch, Bethesda, MD USA.
[Ouwerkerk, Ronald; Gharib, Ahmed M.] Natl Inst Diabet & Digest & Kidney Dis, Biomed & Metab Imaging Branch, Bethesda, MD USA.
[Mari, Andrea] CNR, Inst Biomed Engn, Padua, Italy.
[Walter, Mary] Natl Inst Diabet & Digest & Kidney Dis, Clin Core Lab, Bethesda, MD USA.
[Courville, Amber] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Volkow, Nora D.] NIDA, Intramural Res Program, NIH, Baltimore, MD USA.
[Kunos, George] NIAAA, Lab Physiol Studies, NIH, Rockville, MD 20852 USA.
[Huestis, Marilyn A.] NIAAA, Intramural Program, NIH, Bethesda, MD USA.
RP Skarulis, MC (reprint author), Natl Inst Diabet & Digest & Kidney Dis, Diabet Endocrinol & Obes Branch, Bethesda, MD USA.
EM monicas@intra.niddk.nih.gov
RI Gharib, Ahmed/O-2629-2016;
OI Gharib, Ahmed/0000-0002-2476-481X; Chen, Kong/0000-0002-0306-1904
FU National Institute of Diabetes and Digestive and Kidney Diseases,
National Institute on Drug Abuse; National Institute on Alcohol Abuse
and Alcoholism, National Institutes of Health
FX This work was supported by the Intramural Research Programs of National
Institute of Diabetes and Digestive and Kidney Diseases, National
Institute on Drug Abuse, and National Institute on Alcohol Abuse and
Alcoholism, National Institutes of Health.
NR 49
TC 23
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U1 3
U2 15
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD AUG
PY 2013
VL 36
IS 8
BP 2415
EP 2422
DI 10.2337/dc12-2303
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 255PP
UT WOS:000327252600061
PM 23530011
ER
PT J
AU Wang, Y
Wang, ZF
Hall, TMT
AF Wang, Yang
Wang, Zefeng
Hall, Traci M. Tanaka
TI Engineered proteins with Pumilio/fem-3 mRNA binding factor scaffold to
manipulate RNA metabolism
SO FEBS JOURNAL
LA English
DT Review
DE protein engineering; protein-RNA interaction; PUF protein; RNA; RNA
localization; RNA regulation; RNA-binding protein; splicing;
translation; X-ray crystallography
ID ELEGANS PUF PROTEIN; 3' UNTRANSLATED REGIONS; ALTERNATIVE
POLYADENYLATION; ADENOASSOCIATED VIRUS; SPLICING FACTORS; HOMOLOGY
DOMAIN; RIBONUCLEASE-A; POLYMERASE-II; LIVING CELLS; SPECIFICITY
AB Pumilio/fem-3 mRNA binding factor proteins are characterized by a sequence-specific RNA-binding domain. RNA recognition module, whose sequence specificity can be reprogrammed, has been fused with functional modules to engineer protein factors with various functions. We summarize the advances made with respect to developing RNA regulatory tools, as well as opportunities for the future.
C1 [Wang, Yang; Wang, Zefeng] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Pharmacol, Chapel Hill, NC 27599 USA.
[Hall, Traci M. Tanaka] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Wang, Y (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Pharmacol, Chapel Hill, NC 27599 USA.
EM zefeng@med.unc.edu; hall4@niehs.nih.gov
OI Wang, Zefeng/0000-0002-6605-3637
FU Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences
FX This research was supported in part by the Intramural Research Program
of the NIH, National Institute of Environmental Health Sciences (TMTH).
NR 81
TC 24
Z9 24
U1 3
U2 13
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 AUG
PY 2013
VL 280
IS 16
BP 3755
EP 3767
DI 10.1111/febs.12367
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 253ZM
UT WOS:000327129400003
PM 23731364
ER
PT J
AU Deschamps, MM
Zorrilla, CD
Morgan, CA
Donastorg, Y
Metch, B
Madenwald, T
Joseph, P
Severe, K
Garced, S
Perez, M
Escamilia, G
Swann, E
Pape, JW
AF Deschamps, Marie Marcelle
Zorrilla, Carmen D.
Morgan, Cecilia A.
Donastorg, Yeycy
Metch, Barbara
Madenwald, Tamra
Joseph, Patrice
Severe, Karine
Garced, Sheyla
Perez, Marta
Escamilia, Gina
Swann, Edith
Pape, Jean William
CA HVTN 907 Protocol Team
TI Recruitment of Caribbean female commercial sex workers at high risk of
HIV infection
SO REVISTA PANAMERICANA DE SALUD PUBLICA-PAN AMERICAN JOURNAL OF PUBLIC
HEALTH
LA English
DT Article
DE HIV infections; acquired immunodeficiency syndrome; AIDS vaccines; sex
workers; Caribbean region; Dominican Republic, Haiti, Puerto Rico
ID VACCINE PREPAREDNESS; EFFICACY TRIALS
AB Objective. To evaluate novel eligibility criteria and outreach methods to identify and recruit women at high risk of HIV-1 infection in the Caribbean.
Methods. A prospective cohort study was conducted in 2009-2012 among 799 female commercial sex workers in the Dominican Republic, Haiti, and Puerto Rico. Minimum eligibility criteria included exchange of sex for goods, services, or money in the previous 6 months and unprotected vaginal or anal sex with a man during the same period. Sites used local epidemiology to develop more stringent eligibility criteria and recruitment strategies. Participants were asked questions about HIV/AIDS and their level of concern about participating in an HIV vaccine trial. Logistic regression modeling was used to assess predictors of prevalent HIV infection and willingness to participate in a future HIV vaccine study.
Results. HIV prevalence at screening was 4.6%. Crack cocaine use [odds ratio (OR) = 4.2, 95% confidence interval (CI) (1.8-9.0)] was associated with and having sex with clients in a hotel or motel [OR = 0.5, CI (0.3-1.0)] was inversely associated with HIV infection. A total of 88.9% of enrolled women were definitely or probably willing to participate in a future HIV vaccine trial.
Conclusions. This study indicated that local eligibility criteria and recruitment methods can be developed to identify and recruit commercial sex workers with higher HIV prevalence than the general population who express willingness to join an HIV vaccine trial.
C1 [Deschamps, Marie Marcelle; Joseph, Patrice; Severe, Karine] Grp Haitien Etud Sarcome Kaposi & Infect Opportun, Port Au Prince, Haiti.
[Zorrilla, Carmen D.; Garced, Sheyla] Univ Puerto Rico, Sch Med, Maternal & Infant Studies Ctr, San Juan, PR 00936 USA.
[Morgan, Cecilia A.; Metch, Barbara; Madenwald, Tamra; Escamilia, Gina] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA.
[Donastorg, Yeycy; Perez, Marta] IDCP, Unidad Vacunas, Santo Domingo, Dominican Rep.
[Swann, Edith] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA.
[Pape, Jean William] Weill Cornell Med Coll, Ctr Global Hlth, New York, NY USA.
[HVTN 907 Protocol Team] Fred Hutchinson Canc Res Ctr, HIV Vaccine Trials Network, Seattle, WA 98104 USA.
RP Deschamps, MM (reprint author), Grp Haitien Etud Sarcome Kaposi & Infect Opportun, Port Au Prince, Haiti.
EM mariehd@gheskio.org
FU NIAID NIH HHS [U01 AI068614, UM1 AI068614, UM1 AI068635, UM1 AI069421,
UO1AI068614]
NR 18
TC 6
Z9 6
U1 0
U2 7
PU PAN AMER HEALTH ORGANIZATION
PI WASHINGTON
PA 525 23RD ST NW, WASHINGTON, DC 20037 USA
SN 1020-4989
J9 REV PANAM SALUD PUBL
JI Rev. Panam. Salud Publica
PD AUG
PY 2013
VL 34
IS 2
BP 92
EP 98
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 255PA
UT WOS:000327251100003
PM 24096973
ER
PT J
AU Xu, K
Seo, D
Hodgkinson, C
Hu, Y
Goldman, D
Sinha, R
AF Xu, K.
Seo, D.
Hodgkinson, C.
Hu, Y.
Goldman, D.
Sinha, R.
TI A variant on the kappa opioid receptor gene (OPRK1) is associated with
stress response and related drug craving, limbic brain activation and
cocaine relapse risk
SO TRANSLATIONAL PSYCHIATRY
LA English
DT Article
DE cocaine craving; limbic-midbrain hyperactivation; OPRK1; relapse; stress
ID PITUITARY-ADRENAL AXIS; MIDBRAIN PERIAQUEDUCTAL GRAY; ALCOHOL
DEPENDENCE; NALTREXONE TREATMENT; MESSENGER-RNA; ADDICTION; SYSTEM;
RATS; DYNORPHIN; AGONIST
AB Stress increases drug craving and relapse risk. The kappa opioid receptor gene (OPRK1) mediates stress responses. Here, we examined whether the OPRK1 rs6989250 C>G affects stress-induced cocaine craving and cortisol responses, subsequent cocaine relapse risk and the neural response to stress using functional magnetic resonance imaging (fMRI) in cocaine dependence. Sixty-seven treatment-engaged, abstinent cocaine-dependent African-Americans were genotyped (CG: N = 10; CC: N = 57) and participated in a 3-day experiment in which they were exposed to personalized script-driven imagery of stress, drug cues and neutral scenarios, one condition per day, randomly assigned and counterbalanced across subjects. Repeated measures of craving and cortisol were obtained. The subjects were followed prospectively for 90 days to assess relapse risk. A follow-up preliminary fMRI experiment assessed neural responses to stress, drug cue and neutral conditions in matched CG (N = 5) and CC (N = 8) subgroups. We found greater stress-induced craving (P = 0.019), higher cortisol during stress and cue relative to the neutral condition (P's<0.003), and increased cocaine relapse risk (P = 0.0075) in the CG compared with the CC group. The CG relative to the CC group also showed greater activation of limbic and midbrain regions during stress and cues relative to the neutral condition with additional stress-induced activation in the right amygdala/hippocampus (P<0.05, whole-brain corrected). These results suggest that OPRK1 is associated with stress-induced craving and cortisol, hyperactive hypothalamus/thalamus-midbrain-cerebellum responses, and also associated with greater subsequent cocaine relapse risk. Future studies to replicate these findings in a larger sample size are warranted.
C1 [Xu, K.; Seo, D.; Sinha, R.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06519 USA.
[Hodgkinson, C.; Goldman, D.] NIAAA, Neurogenet Lab, Bethesda, MD USA.
[Hu, Y.] NCI, Ctr Biomed Informat & Informat Tech, Bethesda, MD 20892 USA.
[Sinha, R.] Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06519 USA.
[Sinha, R.] Yale Univ, Stress Ctr, New Haven, CT 06519 USA.
RP Sinha, R (reprint author), Yale Univ, Sch Med, 2 Church St South,Suite 209, New Haven, CT 06519 USA.
EM rajita.sinha@yale.edu
RI Goldman, David/F-9772-2010
OI Goldman, David/0000-0002-1724-5405
FU National Institute on Drug Abuse [P50-DA016556, K12DA000167]; APA/Merck
Early Career Development Award; Department of Mental Health and
Addiction Services of the State of Connecticut
FX This study was supported by the following National Institute on Drug
Abuse grants: P50-DA016556 (RS) and the (K12DA000167) (MP) and the
APA/Merck Early Career Development Award and by the Department of Mental
Health and Addiction Services of the State of Connecticut. We also thank
the staff at the Clinical Neuroscience Research Unit of the Connecticut
Mental Health Center, the Yale Stress Center and the Yale Magnetic
Resonance Research Center (MRRC) for their contribution to this project.
NR 62
TC 14
Z9 14
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 2158-3188
J9 TRANSL PSYCHIAT
JI Transl. Psychiatr.
PD AUG
PY 2013
VL 3
AR e292
DI 10.1038/tp.2013.62
PG 9
WC Psychiatry
SC Psychiatry
GA 258PS
UT WOS:000327471800003
PM 23962922
ER
PT J
AU Partanen, A
Yerram, NK
Trivedi, H
Dreher, MR
Oila, J
Hoang, AN
Volkin, D
Nix, J
Turkbey, B
Bernardo, M
Haines, DC
Benjamin, CJ
Linehan, WM
Choyke, P
Wood, BJ
Ehnholm, GJ
Venkatesan, AM
Pinto, PA
AF Partanen, Ari
Yerram, Nitin K.
Trivedi, Hari
Dreher, Matthew R.
Oila, Juha
Hoang, Anthony N.
Volkin, Dmitry
Nix, Jeffrey
Turkbey, Baris
Bernardo, Marcelino
Haines, Diana C.
Benjamin, Compton J.
Linehan, W. Marston
Choyke, Peter
Wood, Bradford J.
Ehnholm, Gosta J.
Venkatesan, Aradhana M.
Pinto, Peter A.
TI Magnetic resonance imaging (MRI)-guided transurethral ultrasound therapy
of the prostate: a preclinical study with radiological and pathological
correlation using customised MRI-based moulds
SO BJU INTERNATIONAL
LA English
DT Article
DE thermal ablation; therapeutic ultrasound; thermotherapy; minimally
invasive therapy; magnetic resonance imaging; image-guided therapy
ID INTENSITY FOCUSED ULTRASOUND; THERMAL THERAPY; CANCER; HYPERTHERMIA;
SPECIMENS
AB Objective To characterise the feasibility and safety of a novel transurethral ultrasound (US)-therapy device combined with real-time multi-plane magnetic resonance imaging (MRI)-based temperature monitoring and temperature feedback control, to enable spatiotemporally precise regional ablation of simulated prostate gland lesions in a preclinical canine model. To correlate ablation volumes measured with intra-procedural cumulative thermal damage estimates, post-procedural MRI, and histopathology.
Materials and Methods Three dogs were treated with three targeted ablations each, using a prototype MRI-guided transurethral US-therapy system (Philips Healthcare, Vantaa, Finland). MRI provided images for treatment planning, guidance, real-time multi-planar thermometry, as well as post-treatment evaluation of efficacy. After treatment, specimens underwent histopathological analysis to determine the extent of necrosis and cell viability. Statistical analyses (Pearson's correlation, Student's t-test) were used to evaluate the correlation between ablation volumes measured with intra-procedural cumulative thermal damage estimates, post-procedural MRI, and histopathology.
Results MRI combined with a transurethral US-therapy device enabled multi-planar temperature monitoring at the target as well as in surrounding tissues, allowing for safe, targeted, and controlled ablations of prescribed lesions. Ablated volumes measured by cumulative thermal dose positively correlated with volumes determined by histopathological analysis (r(2) 0.83, P < 0.001). Post-procedural contrast-enhanced and diffusion-weighted MRI showed a positive correlation with non-viable areas on histopathological analysis (r(2) 0.89, P < 0.001, and r(2) 0.91, P = 0.003, respectively). Additionally, there was a positive correlation between ablated volumes according to cumulative thermal dose and volumes identified on post-procedural contrast-enhanced MRI (r(2) 0.77, P < 0.01). There was no difference in mean ablation volumes assessed with the various analysis methods (P > 0.05, Student's t-test).
Conclusions MRI-guided transurethral US therapy enabled safe and targeted ablations of prescribed lesions in a preclinical canine prostate model. Ablation volumes were reliably predicted by intra- and post-procedural imaging. Clinical studies are needed to confirm the feasibility, safety, oncological control, and functional outcomes of this therapy in patients in whom focal therapy is indicated.
C1 [Partanen, Ari] Philips Healthcare, Cleveland, OH USA.
[Yerram, Nitin K.; Trivedi, Hari; Hoang, Anthony N.; Volkin, Dmitry; Nix, Jeffrey; Benjamin, Compton J.; Linehan, W. Marston; Pinto, Peter A.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Dreher, Matthew R.; Wood, Bradford J.; Venkatesan, Aradhana M.; Pinto, Peter A.] NIH, Ctr Intervent Oncol Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
[Dreher, Matthew R.; Wood, Bradford J.; Venkatesan, Aradhana M.; Pinto, Peter A.] NCI, Bethesda, MD 20892 USA.
[Turkbey, Baris; Bernardo, Marcelino; Choyke, Peter] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
[Bernardo, Marcelino] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Haines, Diana C.] NCI, Pathol Histotechnol Lab, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA.
[Partanen, Ari] Univ Helsinki, Dept Phys, Helsinki, Finland.
[Oila, Juha; Ehnholm, Gosta J.] Philips Healthcare, Vantaa, Finland.
RP Pinto, PA (reprint author), NCI, Urol Oncol Branch, CRC, 10 Ctr Dr MSC 1210,Bldg 10,Room 2W-5940, Bethesda, MD 20892 USA.
EM pintop@mail.nih.gov
OI Partanen, Ari/0000-0003-1985-149X
FU SalWe Oy/TEKES
FX The authors thank Dr Max Kohler for his advice, and acknowledge support
from SalWe Oy/TEKES. In addition, the authors thank Dr Rajiv Chopra for
his guidance and advice.
NR 28
TC 11
Z9 11
U1 0
U2 19
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1464-4096
EI 1464-410X
J9 BJU INT
JI BJU Int.
PD AUG
PY 2013
VL 112
IS 4
BP 508
EP 516
DI 10.1111/bju.12126
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA 255CZ
UT WOS:000327218200060
PM 23746198
ER
PT J
AU Decker, BK
Palmore, TN
AF Decker, Brooke K.
Palmore, Tara N.
TI The role of water in healthcare-associated infections
SO CURRENT OPINION IN INFECTIOUS DISEASES
LA English
DT Review
DE biofilm; healthcare-associated infection; Legionnaires' disease
ID NOSOCOMIAL LEGIONNAIRES-DISEASE; MYCOBACTERIUM-MUCOGENICUM BACTEREMIA;
LEGIONELLA-PNEUMOPHILA PNEUMONIA; PSEUDOMONAS-AERUGINOSA OUTBREAK;
PEDIATRIC HEMATOLOGY-ONCOLOGY; PATIENTS BATH BASINS; NON-TOUCH FITTINGS;
NONTUBERCULOUS MYCOBACTERIA; STENOTROPHOMONAS-MALTOPHILIA; UNITED-STATES
AB Purpose of reviewThe aim is to discuss the epidemiology of infections that arise from contaminated water in healthcare settings, including Legionnaires' disease, other Gram-negative pathogens, nontuberculous mycobacteria, and fungi.Recent findingsLegionella can colonize a hospital water system and infect patients despite use of preventive disinfectants. Evidence-based measures are available for secondary prevention. Vulnerable patients can develop healthcare-associated infections with waterborne organisms that are transmitted by colonization of plumbing systems, including sinks and their fixtures. Room humidifiers and decorative fountains have been implicated in serious outbreaks, and pose unwarranted risks in healthcare settings.SummaryDesign of hospital plumbing must be purposeful and thoughtful to avoid the features that foster growth and dissemination of Legionella and other pathogens. Exposure of patients who have central venous catheters and other invasive devices to tap water poses a risk for infection with waterborne pathogens. Healthcare facilities must conduct aggressive clinical surveillance for Legionnaires' disease and other waterborne infections in order to detect and remediate an outbreak promptly. Hand hygiene is the most important measure to prevent transmission of other Gram-negative waterborne pathogens in the healthcare setting.
C1 [Decker, Brooke K.; Palmore, Tara N.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Palmore, Tara N.] NIAID, NIH, Bethesda, MD 20892 USA.
RP Palmore, TN (reprint author), 10 Ctr Dr,Room 12C103A, Bethesda, MD 20892 USA.
EM tpalmore@mail.nih.gov
OI Decker M.D., Brooke K/0000-0002-3404-9115
FU Intramural Research Programs of the NIH Clinical Center; National
Institute of Allergy and Infectious Diseases, NIH
FX This research was supported by the Intramural Research Programs of the
NIH Clinical Center and National Institute of Allergy and Infectious
Diseases, NIH.
NR 97
TC 18
Z9 18
U1 6
U2 34
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0951-7375
EI 1473-6527
J9 CURR OPIN INFECT DIS
JI Curr. Opin. Infect. Dis.
PD AUG
PY 2013
VL 26
IS 4
BP 345
EP 351
DI 10.1097/QCO.0b013e3283630adf
PG 7
WC Infectious Diseases
SC Infectious Diseases
GA 248VL
UT WOS:000326733200008
PM 23806897
ER
PT J
AU Turka, LA
Li, XC
Susal, C
AF Turka, Laurence A.
Li, Xian Chang
Suesal, Caner
TI Untitled
SO CURRENT OPINION IN ORGAN TRANSPLANTATION
LA English
DT Editorial Material
C1 [Turka, Laurence A.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Turka, Laurence A.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Turka, Laurence A.] Univ Penn, Philadelphia, PA 19104 USA.
[Turka, Laurence A.; Li, Xian Chang] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Turka, Laurence A.] Amer Soc Transplantat, Mt Laurel, NJ USA.
[Turka, Laurence A.] NIAID, Board Sci Counselors, Bethesda, MD USA.
[Li, Xian Chang] Methodist Hosp, Houston, TX 77030 USA.
[Li, Xian Chang] Methodist Hosp, Transplant Immunol Ctr, Res Inst, Houston, TX 77030 USA.
RP Turka, LA (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1087-2418
EI 1531-7013
J9 CURR OPIN ORGAN TRAN
JI Curr. Opin. Organ Transpl.
PD AUG
PY 2013
VL 18
IS 4
DI 10.1097/MOT.0b013e3283646caa
PG 2
WC Transplantation
SC Transplantation
GA 249AC
UT WOS:000326747400016
ER
PT J
AU Nieman, LK
AF Nieman, Lynnette K.
TI Update in the medical therapy of Cushing's disease
SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY
LA English
DT Review
DE cabergoline; Cushing's disease; mifepristone; pasireotide
ID RETINOIC ACID; SOMATOSTATIN ANALOG; PASIREOTIDE; CABERGOLINE;
ANTAGONIST; DOPAMINE; ACTH
AB Purpose of reviewRecently developed agents treat Cushing's disease by inhibiting ACTH secretion from corticotrope tumors or antagonizing cortisol action.Recent findingsThe dopamine agonist cabergoline and the somatostatin agonist pasireotide target ACTH secretion. Each has low rates of normalization of urine-free cortisol (UFC), about 40% at doses of 1-7mg weekly and 20% at doses of 600 or 900g twice daily, respectively. Cabergoline, an oral agent, has a relatively benign side-effect profile, primarily asthenia. Small trials suggest that combination therapy with ketoconazole increases effectiveness. Pasireotide, a parenteral agent, is associated with types and rates of adverse events similar to those seen with other somatostatin agonists (diarrhea, nausea, cholelithiasis), except for glucose intolerance, which occurs more frequently (approximate to 75%). It may be most effective when UFC is less than two-fold normal. A few case reports suggest that pasireotide or cabergoline may control tumor size and ACTH secretion from macroadenomas. Retinoic acid must be evaluated further. The glucocorticoid antagonist mifepristone ameliorates glucose intolerance but may not normalize other Cushingoid features.SummaryThese novel approaches provide options for treatment of patients in whom surgery has failed or is not possible, and those who decline adrenalectomy or radiation therapy.
RP Nieman, LK (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bldg 10,CRC,1 East,Rm 1-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA.
EM NiemanL@nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD), NIH
FX The intramural program of the Eunice Kennedy Shriver National Institute
of Child Health and Human Development (NICHD), NIH supported this work.
NR 21
TC 17
Z9 17
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1752-296X
EI 1752-2978
J9 CURR OPIN ENDOCRINOL
JI Curr. Opin. Endocrinol. Diabetes Obes.
PD AUG
PY 2013
VL 20
IS 4
BP 330
EP 334
DI 10.1097/MED.0b013e3283631809
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 247BF
UT WOS:000326587600011
PM 23807605
ER
PT J
AU Ostmann, F
Saenz, C
AF Ostmann, Florian
Saenz, Carla
TI SEPARATE GOALS, CONVERGING PRIORITIES: ON THE ETHICS OF TREATMENT AS
PREVENTION
SO DEVELOPING WORLD BIOETHICS
LA English
DT Article
DE bioethics; HIV; AIDS; prevention; treatment; treatment as prevention;
antiretroviral therapy; priority setting
ID TRANSMISSION RISK BEHAVIORS; HIV-1 TRANSMISSION; DISEASE; INFECTION;
DRUGS; STAGE
AB Recent evidence confirming that the administration of antiretroviral drugs (ARVs) to HIV-infected persons may effectively reduce their risk of transmission has revived the discussion about priority setting in the fight against HIV/AIDS. The fact that the very same drugs can be used both for treatment purposes and for preventive purposes (Treatment as Prevention) has been seen as paradigm-shifting and taken to spark a new controversy: In a context of scarce resources, should the allocation of ARVs be prioritized based on the goal of providing treatment, or on the goal of preventing the spread of the HIV epidemic? Contributions to this discussion tend to assume that treatment and prevention constitute two divergent goals that entail conflicting priorities. We challenge that assumption on the basis of both conceptual and empirical examination. We argue that, as far as the provision of ARVs to HIV-infected persons is concerned, the goals of treatment and prevention do not entail conflicting priorities; to the contrary, they dictate converging strategies for the optimal allocation of ARVs. In light of the current evidence, the concept of Treatment as Prevention can indeed be seen as paradigm-shifting, yet in a novel way: Rather than extending the tension between the goals of treatment and prevention to the level of drug-allocation, it dissolves this tension by providing a rationale for a unified strategy for allocating ARVs.
C1 [Ostmann, Florian] UCL, Sch Publ Policy, London WC1E 6BT, England.
[Ostmann, Florian] Pan Amer Hlth Org, Reg HIV STI Project, Washington, DC 20037 USA.
[Saenz, Carla] Pan Amer Hlth Org, Reg Bioeth Program, Washington, DC 20037 USA.
[Saenz, Carla] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD USA.
RP Saenz, C (reprint author), Pan Amer Hlth Org, Reg Bioeth Program, 525 23rd St NW, Washington, DC 20037 USA.
EM saenzcar@paho.org
RI Embrett, Mark/H-4466-2014
OI Embrett, Mark/0000-0002-3969-0219
NR 17
TC 2
Z9 2
U1 1
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1471-8731
EI 1471-8847
J9 DEV WORLD BIOETH
JI Dev. World Bioeth.
PD AUG
PY 2013
VL 13
IS 2
SI SI
BP 57
EP 62
DI 10.1111/dewb.12021
PG 6
WC Ethics; Medical Ethics
SC Social Sciences - Other Topics; Medical Ethics
GA 240HC
UT WOS:000326084900001
PM 23800304
ER
PT J
AU Lindsey, JC
Shah, SK
Siberry, GK
Jean-Philippe, P
Levin, MJ
AF Lindsey, J. C.
Shah, S. K.
Siberry, G. K.
Jean-Philippe, P.
Levin, M. J.
TI ETHICAL TRADEOFFS IN TRIAL DESIGN: CASE STUDY OF AN HPV VACCINE TRIAL IN
HIV-INFECTED ADOLESCENT GIRLS IN LOWER INCOME SETTINGS
SO DEVELOPING WORLD BIOETHICS
LA English
DT Article
DE standard of care; research ethics; public health; vaccines; clinical
trials
ID HUMAN-IMMUNODEFICIENCY-VIRUS; B CONJUGATE VACCINE; HUMAN-PAPILLOMAVIRUS;
DEVELOPING-COUNTRIES; CARE DEBATE; IMMUNOGENICITY; CHILDREN;
TRANSMISSION; STANDARD; TYPE-1
AB The Declaration of Helsinki and the Council of the International Organization of Medical Sciences provide guidance on standards of care and prevention in clinical trials. In the current and increasingly challenging research environment, the ethical status of a trial design depends not only on protection of participants, but also on social value, feasibility, and scientific validity. Using the example of a study assessing efficacy of a vaccine to prevent human papilloma virus in HIV-1 infected adolescent girls in low resource countries without access to the vaccine, we compare several trial designs which rank lower on some criteria and higher on others, giving rise to difficult trade-offs. This case demonstrates the need for developing more nuanced guidance documents to help researchers balance these often conflicting criteria.
C1 [Lindsey, J. C.] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA.
[Levin, M. J.] Univ Colorado, Boulder, CO 80309 USA.
[Siberry, G. K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, MPID Branch, NIH, Bethesda, MD USA.
[Jean-Philippe, P.] NIAID, Maternal Adolescent Pediat Res Branch, DAIDS, NIH, Bethesda, MD USA.
RP Lindsey, JC (reprint author), Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, 665 Huntington Ave, Boston, MA 02115 USA.
EM lindsey@sdac.harvard.edu
FU International Maternal Pediatric Adolescent AIDS Clinical Trials Group
(IMPAACT); National Institute of Allergy and Infectious Diseases (NIAID)
[U01 AI068632]; Eunice Kennedy Shriver National Institute of Child
Health and Human Development (NICHD); National Institute of Mental
Health (NIMH) [AI068632]; Intramural Research Program of the NIH;
Statistical and Data Analysis Center at Harvard School of Public Health,
under the National Institute of Allergy and Infectious Diseases [5 U01
AI41110]; Pediatric AIDS Clinical Trials Group (PACTG) [1 U01 AI068616];
IMPAACT Group; National Institute of Allergies and Infectious Diseases;
National Institutes of Health; Department of Health and Human Services
[HHSN272200800014C]
FX We would like to thank Alan Wertheimer, Doug MacKay, Nicola Barsdorf,
and Rohan Hazra for their helpful comments and suggestions. Overall
support for the International Maternal Pediatric Adolescent AIDS
Clinical Trials Group (IMPAACT) was provided by the National Institute
of Allergy and Infectious Diseases (NIAID) [U01 AI068632], the Eunice
Kennedy Shriver National Institute of Child Health and Human Development
(NICHD), the National Institute of Mental Health (NIMH) [AI068632], and
the Intramural Research Program of the NIH in the Warren G. Magnussen
Clinical Center. This work was supported by the Statistical and Data
Analysis Center at Harvard School of Public Health, under the National
Institute of Allergy and Infectious Diseases cooperative agreement #5
U01 AI41110 with the Pediatric AIDS Clinical Trials Group (PACTG) and #1
U01 AI068616 with the IMPAACT Group. This project has also been
supported with Federal funds from the National Institute of Allergies
and Infectious Diseases, National Institutes of Health, Department of
Health and Human Services, under Contract No. HHSN272200800014C. The
content is solely the responsibility of the authors and does not
necessarily represent the official views of the NIH or the U.S.
Government nor does mention of trade names, commercial practices, or
organizations imply endorsement by the U.S. Government. Some of the
authors are U.S. government employees who must comply with the NIH
Public Access Policy, and the authors or NIH will deposit, or have
deposited, in NIH's PubMed Central archive, an electronic version of the
final, peer-reviewed manuscript upon acceptance for publication, to be
made publicly available no later than 12 months after the official date
of publication.
NR 38
TC 3
Z9 3
U1 1
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1471-8731
EI 1471-8847
J9 DEV WORLD BIOETH
JI Dev. World Bioeth.
PD AUG
PY 2013
VL 13
IS 2
SI SI
BP 95
EP 104
DI 10.1111/dewb.12028
PG 10
WC Ethics; Medical Ethics
SC Social Sciences - Other Topics; Medical Ethics
GA 240HC
UT WOS:000326084900006
PM 23725055
ER
PT J
AU Everett, BM
Pradhan, AD
Solomon, DH
Paynter, N
MacFadyen, J
Zaharris, E
Gupta, M
Clearfield, M
Libby, P
Hasan, AAK
Glynn, RJ
Ridker, PM
AF Everett, Brendan M.
Pradhan, Aruna D.
Solomon, Daniel H.
Paynter, Nina
MacFadyen, Jean
Zaharris, Elaine
Gupta, Milan
Clearfield, Michael
Libby, Peter
Hasan, Ahmed A. K.
Glynn, Robert J.
Ridker, Paul M.
TI Rationale and design of the Cardiovascular Inflammation Reduction Trial:
A test of the inflammatory hypothesis of atherothrombosis
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID C-REACTIVE PROTEIN; TYPE-2 DIABETES-MELLITUS; REVERSE CHOLESTEROL
TRANSPORT; MODIFYING ANTIRHEUMATIC DRUGS; RHEUMATOID-ARTHRITIS;
METABOLIC SYNDROME; MYOCARDIAL-INFARCTION; CORONARY EVENTS; STATIN
THERAPY; RISK
AB Background Inflammation plays a fundamental role in atherothrombosis. Yet, whether direct inhibition of inflammation will reduce the occurrence of adverse cardiovascular outcomes is not known.
Design The Cardiovascular Inflammation Reduction Trial (CIRT) (ClinicalTrials.gov NCT01594333) will randomly allocate 7,000 patients with prior myocardial infarction (MI) and either type 2 diabetes or the metabolic syndrome to low-dose methotrexate (target dose 15-20 mg/wk) or placebo over an average follow-up period of 3 to 5 years. Low-dose methotrexate is a commonly used anti-inflammatory regimen for the treatment of rheumatoid arthritis and lacks significant effects on lipid levels, blood pressure, or platelet function. Both observational and mechanistic studies suggest that low-dose methotrexate has clinically relevant antiatherothrombotic effects. The CIRT primary end point is a composite of nonfatal MI, nonfatal stroke, and cardiovascular death. Secondary end points are all-cause mortality, coronary revascularization plus the primary end point, hospitalization for congestive heart failure plus the primary end point, all-cause mortality plus coronary revascularization plus congestive heart failure plus the primary end point, incident type 2 diabetes, and net clinical benefit or harm. CIRT will use standardized central methodology designed to ensure consistent performance of all dose adjustments and safety interventions at each clinical site in a manner that protects the blinding to treatment but maintains safety for enrolled participants.
Summary CIRT aims to test the inflammatory hypothesis of atherothrombosis in patients with prior MI and either type 2 diabetes or metabolic syndrome, conditions associated with persistent inflammation. If low-dose methotrexate reduces cardiovascular events, CIRT would provide a novel therapeutic approach for the secondary prevention of heart attack, stroke, and cardiovascular death.
C1 [Everett, Brendan M.; Pradhan, Aruna D.; Libby, Peter; Ridker, Paul M.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA.
[Everett, Brendan M.; Paynter, Nina; MacFadyen, Jean; Zaharris, Elaine; Glynn, Robert J.; Ridker, Paul M.] Brigham & Womens Hosp, Div Prevent Med, Ctr Cardiovasc Dis Prevent, Boston, MA 02115 USA.
[Solomon, Daniel H.] Brigham & Womens Hosp, Div Rheumatol, Boston, MA 02115 USA.
[Pradhan, Aruna D.] VA Boston Med Ctr, Div Cardiovasc Med, Boston, MA USA.
[Gupta, Milan] Univ Toronto, Div Cardiol, Toronto, ON, Canada.
[Gupta, Milan] Canadian Cardiovasc Res Network, Toronto, ON, Canada.
[Clearfield, Michael] Touro Univ, Vallejo, CA USA.
[Hasan, Ahmed A. K.] NHLBI, Bethesda, MD 20892 USA.
RP Everett, BM (reprint author), 900 Commonwealth Ave, Boston, MA 02215 USA.
EM beverett@partners.org
OI Gupta, Milan/0000-0002-7385-9006
FU NHLBI NIH HHS [U01 HL101389, U01 HL101422]
NR 48
TC 117
Z9 118
U1 1
U2 14
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
EI 1097-5330
J9 AM HEART J
JI Am. Heart J.
PD AUG
PY 2013
VL 166
IS 2
BP 199
EP +
DI 10.1016/j.ahj.2013.03.018
PG 24
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 194JR
UT WOS:000322629000003
PM 23895801
ER
PT J
AU Ruhl, AP
Lord, RK
Needham, DM
AF Ruhl, A. Parker
Lord, Robert K.
Needham, Dale M.
TI Healthcare Resource Utilization and Costs After Critical Illness:
Current Knowledge and a Plan for Moving Forward
SO CRITICAL CARE MEDICINE
LA English
DT Editorial Material
DE cost of illness; critical care; healthcare costs; patient readmission;
survivors
ID RESPIRATORY-DISTRESS-SYNDROME
C1 [Ruhl, A. Parker; Lord, Robert K.; Needham, Dale M.] Johns Hopkins Univ, Sch Med, Div Pulm & Crit Care Med, Outcomes Crit Illness & Surg OACIS Grp, Baltimore, MD 21218 USA.
[Ruhl, A. Parker] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
[Needham, Dale M.] Johns Hopkins Univ, Sch Med, Dept Phys Med & Rehabil, Baltimore, MD USA.
RP Ruhl, AP (reprint author), Johns Hopkins Univ, Sch Med, Div Pulm & Crit Care Med, Outcomes Crit Illness & Surg OACIS Grp, Baltimore, MD 21218 USA.
NR 11
TC 1
Z9 1
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0090-3493
EI 1530-0293
J9 CRIT CARE MED
JI Crit. Care Med.
PD AUG
PY 2013
VL 41
IS 8
BP 2030
EP 2031
DI 10.1097/CCM.0b013e31828e8edc
PG 2
WC Critical Care Medicine
SC General & Internal Medicine
GA 235FH
UT WOS:000325701500038
PM 23863233
ER
PT J
AU Le Coutre, J
Mattson, MP
Dillin, A
Friedman, J
Bistrian, B
AF Le Coutre, J.
Mattson, M. P.
Dillin, A.
Friedman, J.
Bistrian, B.
TI Nutrition and the biology of human ageing: Cognitive decline/food intake
& caloric restriction
SO JOURNAL OF NUTRITION HEALTH & AGING
LA English
DT Editorial Material
ID ALZHEIMERS-DISEASE; OXIDATIVE STRESS; LEPTIN; INTERMITTENT; DYSFUNCTION;
NEURONS; MARKERS; OBESITY; WOMEN; MODEL
C1 [Le Coutre, J.] Nestle Res Ctr, CH-1000 Lausanne, Switzerland.
[Mattson, M. P.] NIA, Neurosci Lab, Baltimore, MD 21224 USA.
[Dillin, A.] Univ Calif Berkeley, Berkeley, CA 94720 USA.
[Friedman, J.] Rockefeller Univ, New York, NY 10021 USA.
[Bistrian, B.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA.
RP Le Coutre, J (reprint author), Nestle Res Ctr, CH-1000 Lausanne, Switzerland.
EM johannes.le-coutre@rdls.nestle.com
FU NIA NIH HHS [R01 AG027463]
NR 21
TC 1
Z9 1
U1 3
U2 18
PU SPRINGER FRANCE
PI PARIS
PA 22 RUE DE PALESTRO, PARIS, 75002, FRANCE
SN 1279-7707
EI 1760-4788
J9 J NUTR HEALTH AGING
JI J. Nutr. Health Aging
PD AUG
PY 2013
VL 17
IS 8
BP 717
EP 720
DI 10.1007/s12603-013-0375-2
PG 4
WC Geriatrics & Gerontology; Nutrition & Dietetics
SC Geriatrics & Gerontology; Nutrition & Dietetics
GA 231QM
UT WOS:000325432400015
PM 24097030
ER
PT J
AU Anton, BP
Chang, YC
Brown, P
Choi, HP
Faller, LL
Guleria, J
Hu, Z
Klitgord, N
Levy-Moonshine, A
Maksad, A
Mazumdar, V
McGettrick, M
Osmani, L
Pokrzywa, R
Rachlin, J
Swaminathan, R
Allen, B
Housman, G
Monahan, C
Rochussen, K
Tao, K
Bhagwat, AS
Brenner, SE
Columbus, L
de Crecy-Lagard, V
Ferguson, D
Fomenkov, A
Gadda, G
Morgan, RD
Osterman, AL
Rodionov, DA
Rodionova, IA
Rudd, KE
Soll, D
Spain, J
Xu, SY
Bateman, A
Blumenthal, RM
Bollinger, JM
Chang, WS
Ferrer, M
Friedberg, I
Galperin, MY
Gobeill, J
Haft, D
Hunt, J
Karp, P
Klimke, W
Krebs, C
Macelis, D
Madupu, R
Martin, MJ
Miller, JH
O'Donovan, C
Palsson, B
Ruch, P
Setterdahl, A
Sutton, G
Tate, J
Yakunin, A
Tchigvintsev, D
Plata, G
Hu, J
Greiner, R
Horn, D
Sjolander, K
Salzberg, SL
Vitkup, D
Letovsky, S
Segre, D
DeLisi, C
Roberts, RJ
Steffen, M
Kasif, S
AF Anton, Brian P.
Chang, Yi-Chien
Brown, Peter
Choi, Han-Pil
Faller, Lina L.
Guleria, Jyotsna
Hu, Zhenjun
Klitgord, Niels
Levy-Moonshine, Ami
Maksad, Almaz
Mazumdar, Varun
McGettrick, Mark
Osmani, Lais
Pokrzywa, Revonda
Rachlin, John
Swaminathan, Rajeswari
Allen, Benjamin
Housman, Genevieve
Monahan, Caitlin
Rochussen, Krista
Tao, Kevin
Bhagwat, Ashok S.
Brenner, Steven E.
Columbus, Linda
de Crecy-Lagard, Valerie
Ferguson, Donald
Fomenkov, Alexey
Gadda, Giovanni
Morgan, Richard D.
Osterman, Andrei L.
Rodionov, Dmitry A.
Rodionova, Irina A.
Rudd, Kenneth E.
Soll, Dieter
Spain, James
Xu, Shuang-Yong
Bateman, Alex
Blumenthal, Robert M.
Bollinger, J. Martin
Chang, Woo-Suk
Ferrer, Manuel
Friedberg, Iddo
Galperin, Michael Y.
Gobeill, Julien
Haft, Daniel
Hunt, John
Karp, Peter
Klimke, William
Krebs, Carsten
Macelis, Dana
Madupu, Ramana
Martin, Maria J.
Miller, Jeffrey H.
O'Donovan, Claire
Palsson, Bernhard
Ruch, Patrick
Setterdahl, Aaron
Sutton, Granger
Tate, John
Yakunin, Alexander
Tchigvintsev, Dmitri
Plata, German
Hu, Jie
Greiner, Russell
Horn, David
Sjolander, Kimmen
Salzberg, Steven L.
Vitkup, Dennis
Letovsky, Stanley
Segre, Daniel
DeLisi, Charles
Roberts, Richard J.
Steffen, Martin
Kasif, Simon
TI The COMBREX Project: Design, Methodology, and Initial Results
SO PLOS BIOLOGY
LA English
DT Editorial Material
ID GENOME ANNOTATION; PROTEIN FUNCTION; TRANSFER-RNA; DATABASE; FAMILIES;
ENZYME
C1 New England Biolabs Inc, Ipswich, MA USA.
[Chang, Yi-Chien; Faller, Lina L.; Hu, Zhenjun; Klitgord, Niels; Mazumdar, Varun; Letovsky, Stanley; Segre, Daniel; DeLisi, Charles; Roberts, Richard J.; Kasif, Simon] Boston Univ, Bioinformat Program, Boston, MA 02215 USA.
[Brown, Peter; Choi, Han-Pil; Guleria, Jyotsna; Levy-Moonshine, Ami; Maksad, Almaz; Osmani, Lais; Pokrzywa, Revonda; Swaminathan, Rajeswari; Housman, Genevieve; Monahan, Caitlin; Rochussen, Krista; Tao, Kevin; Steffen, Martin; Kasif, Simon] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA.
[McGettrick, Mark; Rachlin, John] Diatom Software LLC, Holliston, MA USA.
[Allen, Benjamin] Harvard Univ, Program Evolutionary Dynam, Cambridge, MA 02138 USA.
[Allen, Benjamin] Univ Cambridge Emmanuel Coll, Dept Math, Boston, MA USA.
[Bhagwat, Ashok S.] Wayne State Univ, Dept Chem, Detroit, MI 48202 USA.
[Brenner, Steven E.] Univ Calif Berkeley, Dept Plant & Microbial Sci, Berkeley, CA 94720 USA.
[Columbus, Linda] Univ Virginia, Dept Chem, Charlottesville, VA USA.
[de Crecy-Lagard, Valerie] Univ Florida, Dept Microbiol & Cell Sci, Gainesville, FL 32611 USA.
[Ferguson, Donald; Friedberg, Iddo] Miami Univ, Dept Microbiol, Oxford, OH 45056 USA.
[Gadda, Giovanni] Georgia State Univ, Dept Chem, Atlanta, GA 30303 USA.
[Osterman, Andrei L.; Rodionov, Dmitry A.; Rodionova, Irina A.] Sanford Burnham Med Res Inst, La Jolla, CA USA.
[Rudd, Kenneth E.] Univ Miami, Dept Biochem & Mol Biol, Miami, FL 33101 USA.
[Soll, Dieter] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT USA.
[Spain, James] Georgia Inst Technol, Sch Civil & Environm Engn, Atlanta, GA 30332 USA.
[Bateman, Alex; Martin, Maria J.; O'Donovan, Claire] Wellcome Trust Genome Campus, European Bioinformat Inst, Hinxton, Cambridgeshire, England.
[Blumenthal, Robert M.] Univ Toledo, Dept Med Microbiol & Immunol, Toledo, OH 43606 USA.
[Blumenthal, Robert M.] Univ Toledo, Program Bioinformat, Toledo, OH 43606 USA.
[Bollinger, J. Martin; Krebs, Carsten] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA.
[Chang, Woo-Suk] Univ Texas Arlington, Dept Biol, Arlington, TX 76019 USA.
[Ferrer, Manuel] Inst Catalysis, Spanish Natl Res Council CSIC, Madrid, Spain.
[Galperin, Michael Y.; Klimke, William] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA.
[Gobeill, Julien; Ruch, Patrick] Univ Appl Sci Western Switzerland, Dept Lib & Informat Studies, Geneva, Switzerland.
[Gobeill, Julien; Ruch, Patrick] Swiss Inst Bioinformat, Bibli & Text Min Grp, Geneva, Switzerland.
[Haft, Daniel; Madupu, Ramana; Sutton, Granger] J Craig Venter Inst, Rockville, MD USA.
[Hunt, John] Columbia Univ, New York, NY USA.
[Karp, Peter] SRI Int, Ctr Artificial Intelligence, Bioinformat Res Grp, Menlo Pk, CA 94025 USA.
[Miller, Jeffrey H.] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA USA.
[Palsson, Bernhard] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA.
[Setterdahl, Aaron] Indiana Univ SE, Dept Chem, New Albany, IN 47150 USA.
[Tate, John] Wellcome Trust Genome Campus, Wellcome Trust Sanger Inst, Hinxton, Cambridgeshire, England.
[Yakunin, Alexander; Tchigvintsev, Dmitri] Univ Toronto, Dept Chem Engn & Appl Chem, Toronto, ON, Canada.
[Plata, German; Hu, Jie; Vitkup, Dennis] Columbia Univ, Ctr Computat Biol & Bioinformat, New York, NY USA.
[Plata, German] Columbia Univ, Integrated Program Cellular Mol Struct & Genet St, New York, NY USA.
[Greiner, Russell] Univ Alberta, Dept Comp Sci, Edmonton, AB, Canada.
[Horn, David] Tel Aviv Univ, Sch Phys & Astron, IL-69978 Tel Aviv, Israel.
[Sjolander, Kimmen] Univ Calif Berkeley, Berkeley Phylogen Grp, Berkeley, CA 94720 USA.
[Salzberg, Steven L.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Dept Med, Baltimore, MD USA.
[Salzberg, Steven L.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Dept Biostat, Baltimore, MD USA.
RP Anton, BP (reprint author), New England Biolabs Inc, Ipswich, MA USA.
EM anton@neb.com; kasif@bu.edu
RI Hu, Jie/J-5075-2012; Yakunin, Alexander/J-1519-2014; Krebs,
Carsten/D-4773-2009; Hu, Zhigao/J-4875-2012; Bollinger, Joseph
/C-1425-2016; Salzberg, Steven/F-6162-2011; Brenner, Steven/A-8729-2008;
OI Roberts, Richard/0000-0002-4348-0169; Rodionov,
Dmitry/0000-0002-0939-390X; Plata, German/0000-0002-6470-7748; Ruch,
Patrick/0000-0002-3374-2962; Krebs, Carsten/0000-0002-3302-7053;
Salzberg, Steven/0000-0002-8859-7432; Brenner,
Steven/0000-0001-7559-6185; Steffen, Martin/0000-0002-7853-7364;
Bateman, Alex/0000-0002-6982-4660; Ferrer, Manuel/0000-0003-4962-4714;
Yakunin, Alexander/0000-0003-0813-6490; Karp, Peter/0000-0002-5876-6418;
Friedberg, Iddo/0000-0002-1789-8000; Columbus,
Linda/0000-0002-2574-0561; Martin, Maria-Jesus/0000-0001-5454-2815;
Allen, Benjamin/0000-0002-9746-7613; O'Donovan,
Claire/0000-0001-8051-7429; Galperin, Michael/0000-0002-2265-5572
FU National Institute of General Medical Sciences (NIGMS) [1RC2GM092602-01]
FX COMBREX is funded by a GO grant from the National Institute of General
Medical Sciences (NIGMS) (1RC2GM092602-01). The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 31
TC 22
Z9 23
U1 0
U2 19
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 AUG
PY 2013
VL 11
IS 8
AR e1001638
DI 10.1371/journal.pbio.1001638
PG 8
WC Biochemistry & Molecular Biology; Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics
GA 209PR
UT WOS:000323771900016
PM 24013487
ER
PT J
AU Freedman, DM
Kuncl, RW
Weinstein, SJ
Albanes, D
AF Freedman, D. Michal
Kuncl, Ralph W.
Weinstein, Stephanie J.
Albanes, Demetrius
TI Comment on "Intakes of Vitamin C and Carotenoids and Risk of Amyotrophic
Lateral Sclerosis: Pooled Results from 5 Cohort Studies"
SO ANNALS OF NEUROLOGY
LA English
DT Letter
C1 [Freedman, D. Michal; Weinstein, Stephanie J.; Albanes, Demetrius] NCI, Dept Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Kuncl, Ralph W.] Univ Redlands, Dept Biol, Redlands, CA 92373 USA.
RP Freedman, DM (reprint author), NCI, Dept Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RI Albanes, Demetrius/B-9749-2015
FU Intramural NIH HHS [Z99 CA999999]
NR 3
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0364-5134
J9 ANN NEUROL
JI Ann. Neurol.
PD AUG
PY 2013
VL 74
IS 2
BP 307
EP 307
DI 10.1002/ana.23955
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 224XO
UT WOS:000324925900024
PM 23775975
ER
PT J
AU Henderson, MK
Simeon-Dubach, D
Zaayenga, A
AF Henderson, Marianne K.
Simeon-Dubach, Daniel
Zaayenga, Andy
TI When Bad Things Happen: Lessons Learned from Effective and not so
Effective Disaster and Recovery Planning for Biobanks
SO BIOPRESERVATION AND BIOBANKING
LA English
DT Editorial Material
C1 [Henderson, Marianne K.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
[Simeon-Dubach, Daniel] Medserv Biobanking Consulting & Serv, Walchwil, Switzerland.
[Zaayenga, Andy] Lab Automat Consulting, SmarterLab, Martinsville, NJ USA.
RP Henderson, MK (reprint author), NCI, Off Div Operat & Anal, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA.
EM hendersm@mail.nih.gov
NR 0
TC 1
Z9 1
U1 0
U2 3
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1947-5535
J9 BIOPRESERV BIOBANK
JI Biopreserv. Biobank.
PD AUG 1
PY 2013
VL 11
IS 4
BP 193
EP 193
DI 10.1089/bio.2013.1141
PG 1
WC Cell Biology; Chemistry, Applied; Medical Laboratory Technology
SC Cell Biology; Chemistry; Medical Laboratory Technology
GA 224GG
UT WOS:000324870300001
PM 24845583
ER
PT J
AU Cole, TG
Contois, JH
Csako, G
McConnell, JP
Remaley, AT
Devaraj, S
Hoefner, DM
Mallory, T
Sethi, AA
Warnick, GR
AF Cole, Thomas G.
Contois, John H.
Csako, Gyorgy
McConnell, Joseph P.
Remaley, Alan T.
Devaraj, Sridevi
Hoefner, Daniel M.
Mallory, Tonya
Sethi, Amar A.
Warnick, G. Russell
TI Apolipoprotein B and Nuclear Magnetic Resonance Particle Number Reply
SO CLINICAL CHEMISTRY
LA English
DT Letter
ID DIVISION WORKING GROUP; LIPOPROTEIN; MARKERS; RISK
C1 [Cole, Thomas G.] Thom Cole Consulting LLC, St Louis, MO 63122 USA.
[Contois, John H.] Sun Diagnost LLC, New Gloucester, ME USA.
[Csako, Gyorgy; Remaley, Alan T.] NIH, Dept Lab Med, Bethesda, MD 20892 USA.
[McConnell, Joseph P.; Hoefner, Daniel M.; Mallory, Tonya; Warnick, G. Russell] Hlth Diagnost Lab Inc, Richmond, VA USA.
[Devaraj, Sridevi] Texas Childrens Hosp, Dept Clin Chem, Houston, TX 77030 USA.
[Sethi, Amar A.] Pacific Biomarkers Inc, Seattle, WA USA.
RP Cole, TG (reprint author), Thom Cole Consulting LLC, 594 Gederson Lane, St Louis, MO 63122 USA.
EM tgchol@aol.com
NR 4
TC 0
Z9 0
U1 0
U2 2
PU AMER ASSOC CLINICAL CHEMISTRY
PI WASHINGTON
PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA
SN 0009-9147
EI 1530-8561
J9 CLIN CHEM
JI Clin. Chem.
PD AUG
PY 2013
VL 59
IS 8
BP 1277
EP 1278
DI 10.1373/clinchem.2013.209247
PG 3
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 231EW
UT WOS:000325398100024
PM 24049794
ER
PT J
AU Yoshinaga, K
AF Yoshinaga, Koji
TI A sequence of events in the uterus prior to implantation in the mouse
SO JOURNAL OF ASSISTED REPRODUCTION AND GENETICS
LA English
DT Article
DE Embryo spacing; Zona shedding; Luminal closure
ID EMBRYO IMPLANTATION; ZONA-PELLUCIDA; BLASTOCYST IMPLANTATION;
EARLY-PREGNANCY; ESTROUS-CYCLE; IN-VITRO; RAT; PROGESTERONE;
PROSTAGLANDINS; GROWTH
AB I reviewed a series of events in the mouse uterus before implantation on Day 4 of pregnancy (the sperm positive day is counted as Day 1). Major events are spacing of embryos along the uterine horns, shedding of the zona pellucida, and closure of the uterine lumen. How subtle they may be, there appear to exist interactions between intrauterine blastocysts and the uterus which is regulated by ovarian steroids. Spacing of embryos along the uterine horn is not random, but they are rather evenly distributed along the entire horn. The mechanism of even distribution of embryos needs clarification, although studies indicate that adrenergic nerve activity, prostaglandins, and other molecules appear to be involved. Shedding of the zona pellucida involves trypsin-like proteinase lysis of the zona. Through the opening created by zona lysis, blastocyst gets out of the zona by repeating expansion-collapse movements. Closure of rat uterine lumen is reported to be the result of absorption of uterine fluid through uterine glands. This needs to be confirmed in other species of rodents. Since these events influence blastocyst implantation, we need more detailed information on their regulatory mechanisms in order to improve the rate of healthy implantation of transferred embryo.
C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Fertil & Infertil Branch, NIH, DHHS, Bethesda, MD 20892 USA.
RP Yoshinaga, K (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Fertil & Infertil Branch, NIH, DHHS, Bldg 6100,Rm 8B01, Bethesda, MD 20892 USA.
EM ky6a@nih.gov
NR 45
TC 8
Z9 8
U1 2
U2 5
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1058-0468
EI 1573-7330
J9 J ASSIST REPROD GEN
JI J. Assist. Reprod. Genet.
PD AUG
PY 2013
VL 30
IS 8
SI SI
BP 1017
EP 1022
DI 10.1007/s10815-013-0093-z
PG 6
WC Genetics & Heredity; Obstetrics & Gynecology; Reproductive Biology
SC Genetics & Heredity; Obstetrics & Gynecology; Reproductive Biology
GA 228YS
UT WOS:000325228700005
PM 24052329
ER
PT J
AU Chen, JW
Feng, G
Guo, Q
Wardenburg, JB
Lin, S
Inoshima, I
Deaton, R
Yuan, JXJ
Garcia, JGN
Machado, RF
Otto, M
Wunderink, RG
AF Chen, Jiwang
Feng, Gang
Guo, Qiang
Wardenburg, Juliane B.
Lin, Simon
Inoshima, Ichiro
Deaton, Ryan
Yuan, Jason X. J.
Garcia, Joe G. N.
Machado, Roberto F.
Otto, Michael
Wunderink, Richard G.
TI Transcriptional Events during the Recovery from MRSA Lung Infection: A
Mouse Pneumonia Model
SO PLOS ONE
LA English
DT Article
ID PANTON-VALENTINE LEUKOCIDIN; STAPHYLOCOCCUS-AUREUS; ILLUMINA MICROARRAY;
DISEASE-ONTOLOGY; HOST-DEFENSE; CELL-GROWTH; PROTEIN; GENE; INHIBITOR;
RECEPTOR
AB Community associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is an emerging threat to human health throughout the world. Rodent MRSA pneumonia models mainly focus on the early innate immune responses to MRSA lung infection. However, the molecular pattern and mechanisms of recovery from MRSA lung infection are largely unknown. In this study, a sublethal mouse MRSA pneumonia model was employed to investigate late events during the recovery from MRSA lung infection. We compared lung bacterial clearance, bronchoalveolar lavage fluid (BALF) characterization, lung histology, lung cell proliferation, lung vascular permeability and lung gene expression profiling between days 1 and 3 post MRSA lung infection. Compared to day 1 post infection, bacterial colony counts, BALF total cell number and BALF protein concentration significantly decreased at day 3 post infection. Lung cDNA microarray analysis identified 47 significantly upregulated and 35 down-regulated genes (p<0.01, 1.5 fold change [up and down]). The pattern of gene expression suggests that lung recovery is characterized by enhanced cell division, vascularization, wound healing and adjustment of host adaptive immune responses. Proliferation assay by PCNA staining further confirmed that at day 3 lungs have significantly higher cell proliferation than at day 1. Furthermore, at day 3 lungs displayed significantly lower levels of vascular permeability to albumin, compared to day 1. Collectively, this data helps us elucidate the molecular mechanisms of the recovery after MRSA lung infection.
C1 [Chen, Jiwang; Wunderink, Richard G.] Northwestern Univ, Dept Med, Chicago, IL 60611 USA.
[Chen, Jiwang; Guo, Qiang; Yuan, Jason X. J.; Garcia, Joe G. N.; Machado, Roberto F.] Univ Illinois, Sect Pulm Crit Care Med Allergy & Sleep, Chicago, IL USA.
[Feng, Gang; Lin, Simon] Northwestern Univ, Biomed Informat Ctr, Chicago, IL 60611 USA.
[Wardenburg, Juliane B.; Inoshima, Ichiro] Univ Chicago, Dept Pediat, Chicago, IL 60637 USA.
[Lin, Simon] Marshfield Clin Res Fdn, Biomed Informat Res Ctr, Marshfield, WI USA.
[Deaton, Ryan] Univ Illinois, Dept Pathol, Chicago, IL USA.
[Otto, Michael] NIAID, Bethesda, MD 20892 USA.
RP Chen, JW (reprint author), Northwestern Univ, Dept Med, Chicago, IL 60611 USA.
EM chenjw@uic.edu
OI Otto, Michael/0000-0002-2222-4115; Wunderink,
Richard/0000-0002-8527-4195
FU Pfizer ASPIRE Award; Pfizer Investigator-Initiated Grant [WS1826185];
National Center for Advancing Translational Sciences Grant
[8UL1TR000150]; NCI Cancer Center Support Grant [NCI CA060553];
Intramural Research Program of the NIAID
FX This study was supported by Pfizer ASPIRE Award, Pfizer
Investigator-Initiated Grant (WS1826185, to Chen), the National Center
for Advancing Translational Sciences Grant (8UL1TR000150) and the NCI
Cancer Center Support Grant (NCI CA060553 to Feng and Lin) and the
Intramural Research Program of the NIAID (to Otto). The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 57
TC 3
Z9 3
U1 0
U2 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 AUG 1
PY 2013
VL 8
IS 8
AR e70176
DI 10.1371/journal.pone.0070176
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 219PB
UT WOS:000324518400041
PM 23936388
ER
PT J
AU Li, LN
Dimitriadis, EK
Yang, Y
Li, J
Yuan, ZH
Qiao, CP
Beley, C
Smith, RH
Garcia, L
Kotin, RM
AF Li, Lina
Dimitriadis, Emilios K.
Yang, Yu
Li, Juan
Yuan, Zhenhua
Qiao, Chunping
Beley, Cyriaque
Smith, Richard H.
Garcia, Luis
Kotin, Robert M.
TI Production and Characterization of Novel Recombinant Adeno-Associated
Virus Replicative-Form Genomes: A Eukaryotic Source of DNA for Gene
Transfer
SO PLOS ONE
LA English
DT Article
ID PLASMID DNA; ESCHERICHIA-COLI; IMMUNE-RESPONSES; IN-VITRO; EFFICIENT
TRANSDUCTION; VIRAL VECTORS; INSECT CELLS; REP PROTEIN; THERAPY;
TOLL-LIKE-RECEPTOR-9
AB Conventional non-viral gene transfer uses bacterial plasmid DNA containing antibiotic resistance genes, cis-acting bacterial sequence elements, and prokaryotic methylation patterns that may adversely affect transgene expression and vector stability in vivo. Here, we describe novel replicative forms of a eukaryotic vector DNA that consist solely of an expression cassette flanked by adeno-associated virus (AAV) inverted terminal repeats. Extensive structural analyses revealed that this AAV-derived vector DNA consists of linear, duplex molecules with covalently closed ends (termed closed-ended, linear duplex, or "CELiD'', DNA). CELiD vectors, produced in Sf9 insect cells, require AAV rep gene expression for amplification. Amounts of CELiD DNA produced from insect cell lines stably transfected with an ITR-flanked transgene exceeded 60 mg per 5x10(9) Sf9 cells, and 1-15 mg from a comparable number of parental Sf9 cells in which the transgene was introduced via recombinant baculovirus infection. In mice, systemically delivered CELiD DNA resulted in long-term, stable transgene expression in the liver. CELiD vectors represent a novel eukaryotic alternative to bacterial plasmid DNA.
C1 [Li, Lina; Yang, Yu; Smith, Richard H.; Kotin, Robert M.] NHLBI, Lab Mol Virol & Gene Therapy, NIH, Bethesda, MD 20892 USA.
[Dimitriadis, Emilios K.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA.
[Li, Juan; Yuan, Zhenhua; Qiao, Chunping] Univ N Carolina, Sch Pharm, Chapel Hill, NC USA.
[Beley, Cyriaque; Garcia, Luis] Univ Versailles, Fac Hlth Sci, St Quentin En Yvelines, France.
RP Kotin, RM (reprint author), NHLBI, Lab Mol Virol & Gene Therapy, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM kotinr@nhlbi.nih.gov
FU National Heart, Lung, and Blood Institute (RMK); National Institute of
Biomedical Engineering Imaging and Bioengineering; National Institutes
of Health; International Collaborative Effort (ICE) for Duchenne
Muscular Dystrophy; Duchenne Parent 1 Project France; Association
Monegasquecontre les Myopathies
FX This work was funded by Intramural Research Programs of the National
Heart, Lung, and Blood Institute (RMK) and National Institute of
Biomedical Engineering Imaging and Bioengineering (EKD) of the National
Institutes of Health. The International Collaborative Effort (ICE) for
Duchenne Muscular Dystrophy, the Duchenne Parent 1 Project France, and
the Association Monegasquecontre les Myopathies (RMK and LG) provided
additional funds. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 44
TC 2
Z9 5
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 AUG 1
PY 2013
VL 8
IS 8
AR e69879
DI 10.1371/journal.pone.0069879
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 219PB
UT WOS:000324518400026
PM 23936358
ER
PT J
AU Peng, XJ
Li, WP
Yuan, L
Mehta, RG
Kopelovich, L
McCormick, DL
AF Peng, Xinjian
Li, Wenping
Yuan, Liang
Mehta, Rajendra G.
Kopelovich, Levy
McCormick, David L.
TI Inhibition of Proliferation and Induction of Autophagy by Atorvastatin
in PC3 Prostate Cancer Cells Correlate with Downregulation of Bcl2 and
Upregulation of miR-182 and p21
SO PLOS ONE
LA English
DT Article
ID BREAST-CANCER; ANDROGEN INDEPENDENCE; VITAMIN-D; EXPRESSION; STATINS;
GENE; MICRORNA-182; PROTEIN; ADENOCARCINOMA; HOMEOSTASIS
AB The epidemiologic association between statin use and decreased risk of advanced prostate cancer suggests that statins may inhibit prostate cancer development and/or progression. Studies were performed to determine the effects of a model statin, atorvastatin ( ATO), on the proliferation and differentiation of prostate cancer cells, and to identify possible mechanisms of ATO action. ATO inhibited the in vitro proliferation of both LNCaP and PC3 human prostate cancer cells in a dose- and time-dependent fashion. The greater inhibitory activity of ATO in PC3 cells was associated with induction of autophagy in that cell line, as demonstrated by increased expression of LC3-II. miR-182 was consistently upregulated by ATO in PC3 cells, but not in LNCaP cells. ATO upregulation of miR-182 in PC3 cells was p53-independent and was reversed by geranylgeraniol. Transfection of miR-182 inhibitors decreased expression of miR-182 by > 98% and attenuated the antiproliferative activity of ATO. miR-182 expression in PC3 cells was also increased in response to stress induced by serum withdrawal, suggesting that miR-182 upregulation can occur due to nutritional stress. Bcl2 and p21 were identified to be potential target genes of miR-182 in PC3 cells. Bcl2 was downregulated and p21 was upregulated in PC3 cells exposed to ATO. These data suggest that miR-182 may be a stress-responsive miRNA that mediates ATO action in prostate cancer cells.
C1 [Peng, Xinjian; Li, Wenping; Yuan, Liang; Mehta, Rajendra G.; McCormick, David L.] IIT Res Inst, Life Sci Grp, Chicago, IL USA.
[Kopelovich, Levy] NCI, Chemoprevent Agent Dev Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Peng, XJ (reprint author), IIT Res Inst, Life Sci Grp, Chicago, IL USA.
EM xpeng@iitri.org
FU Division of Cancer Prevention, National Cancer Institute, Department of
Health and Human Services [N01-CN-43303]
FX This work was supported by contract N01-CN-43303 from the Division of
Cancer Prevention, National Cancer Institute, Department of Health and
Human Services. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 45
TC 23
Z9 24
U1 4
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 AUG 1
PY 2013
VL 8
IS 8
AR e70442
DI 10.1371/journal.pone.0070442
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 219PB
UT WOS:000324518400068
PM 23936432
ER
PT J
AU Xiong, WH
Duvoisin, RM
Adamus, G
Jeffrey, BG
Gellman, C
Morgans, CW
AF Xiong, Wei-Hong
Duvoisin, Robert M.
Adamus, Grazyna
Jeffrey, Brett G.
Gellman, Celia
Morgans, Catherine W.
TI Serum TRPM1 Autoantibodies from Melanoma Associated Retinopathy Patients
Enter Retinal ON-Bipolar Cells and Attenuate the Electroretinogram in
Mice
SO PLOS ONE
LA English
DT Article
ID CUTANEOUS MALIGNANT-MELANOMA; PARANEOPLASTIC RETINOPATHY; NIGHT
BLINDNESS; LIGHT RESPONSE; IN-VIVO; ANTIBODIES; CHANNELS; CASCADE; ROD
AB Melanoma-associated retinopathy (MAR) is a paraneoplastic syndrome associated with cutaneous malignant melanoma and the presence of autoantibodies that label neurons in the inner retina. The visual symptoms and electroretinogram (ERG) phenotype characteristic of MAR resemble the congenital visual disease caused by mutations in TRPM1, a cation channel expressed by both melanocytes and retinal bipolar cells. Four serum samples from MAR patients were identified as TRPM1 immunoreactive by 1. Labeling of ON-bipolar cells in TRPM1+/+ but not TRPM1-/- mouse retina, 2. Labeling of TRPM1-transfected CHO cells; and 3. Attenuation of the ERG b-wave following intravitreal injection of TRPM1-positive MAR IgG into wild-type mouse eyes, and the appearance of the IgG in the retinal bipolar cells at the conclusion of the experiment. Furthermore, the epitope targeted by the MAR autoantibodies was localized within the amino-terminal cytoplasmic domain of TRPM1. Incubation of live retinal neurons with TRPM1-positive MAR serum resulted in the selective accumulation of IgG in ON-bipolar cells from TRPM1+/+ mice, but not TRPM1-/- mice, suggesting that the visual deficits in MAR are caused by the uptake of TRPM1 autoantibodies into ON-bipolar cells, where they bind to an intracellular epitope of the channel and reduce the ON-bipolar cell response to light.
C1 [Xiong, Wei-Hong; Adamus, Grazyna; Gellman, Celia; Morgans, Catherine W.] Oregon Hlth & Sci Univ, Casey Eye Inst, Portland, OR 97201 USA.
[Duvoisin, Robert M.; Morgans, Catherine W.] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97201 USA.
[Jeffrey, Brett G.] NEI, NIH, Bethesda, MD 20892 USA.
RP Morgans, CW (reprint author), Oregon Hlth & Sci Univ, Casey Eye Inst, Portland, OR 97201 USA.
EM morgansc@ohsu.edu
FU OCTRI, Medical Research Foundation of Oregon [NIHR01EY018625,
NIHR01EY022369, NIH5P30EY010572]
FX This research was supported by the following grants: NIHR01EY018625
(CWM), NIHR01EY022369 (CWM), OCTRI, Medical Research Foundation of
Oregon, NIH5P30EY010572. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 35
TC 10
Z9 10
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 AUG 1
PY 2013
VL 8
IS 8
AR e69506
DI 10.1371/journal.pone.0069506
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 219PB
UT WOS:000324518400015
PM 23936334
ER
PT J
AU Suomi, S
AF Suomi, S.
TI Epigenetic consequences of adverse early social experiences in primates
SO SOUTH AFRICAN JOURNAL OF PSYCHIATRY
LA English
DT Meeting Abstract
C1 [Suomi, S.] NICHD, NIH, Comparat Ethol Lab, Bethesda, MD USA.
EM suomis@lce.nichd.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 2
PU SA MEDICAL ASSOC HEALTH & MEDICAL PUBL GROUP
PI CLAREMONT
PA 21 DREYER ST, 4TH FLOOR, SANCLARE BLDG, CLAREMONT, 7700, SOUTH AFRICA
SN 1608-9685
J9 SAJP-S AFR J PSYCHI
JI SAJP
PD AUG
PY 2013
VL 19
IS 3
BP 109
EP 109
PG 1
WC Psychiatry
SC Psychiatry
GA 228ZO
UT WOS:000325231800062
ER
PT J
AU Suomi, S
AF Suomi, S.
TI Risk, resilience, and gene x environment interactions in primates
SO SOUTH AFRICAN JOURNAL OF PSYCHIATRY
LA English
DT Meeting Abstract
C1 [Suomi, S.] NICHD, NIH, Comparat Ethol Lab, Bethesda, MD USA.
EM suomis@lce.nichd.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 2
PU SA MEDICAL ASSOC HEALTH & MEDICAL PUBL GROUP
PI CLAREMONT
PA 21 DREYER ST, 4TH FLOOR, SANCLARE BLDG, CLAREMONT, 7700, SOUTH AFRICA
SN 1608-9685
J9 SAJP-S AFR J PSYCHI
JI SAJP
PD AUG
PY 2013
VL 19
IS 3
BP 109
EP 109
PG 1
WC Psychiatry
SC Psychiatry
GA 228ZO
UT WOS:000325231800063
ER
PT J
AU Suman, S
Rodriguez, OC
Winters, TA
Fornace, AJ
Albanese, C
Datta, K
AF Suman, Shubhankar
Rodriguez, Olga C.
Winters, Thomas A.
Fornace, Albert J., Jr.
Albanese, Chris
Datta, Kamal
TI Therapeutic and space radiation exposure of mouse brain causes impaired
DNA repair response and premature senescence by chronic oxidant
production
SO AGING-US
LA English
DT Article
DE Radiation; heavy ion radiation; premature aging; senescence; oxidative
stress; DNA damage; cerebral cortex; long-term effects
ID NEURAL PRECURSOR CELLS; OXIDATIVE STRESS; ALZHEIMERS-DISEASE;
CANCER-RISKS; FE-56-PARTICLE RADIATION; HIPPOCAMPAL NEUROGENESIS;
INTERMEDIATE-FILAMENT; COMPUTED-TOMOGRAPHY; CELLULAR SENESCENCE;
IONIZING-RADIATION
AB Despite recent epidemiological evidences linking radiation exposure and a number of human ailments including cancer, mechanistic understanding of how radiation inflicts long-term changes in cerebral cortex, which regulates important neuronal functions, remains obscure. The current study dissects molecular events relevant to pathology in cerebral cortex of 6 to 8 weeks old female C57BL/6J mice two and twelve months after exposure to a gamma radiation dose (2 Gy) commonly employed in fractionated radiotherapy. For a comparative study, effects of 1.6 Gy heavy ion Fe-56 radiation on cerebral cortex were also investigated, which has implications for space exploration. Radiation exposure was associated with increased chronic oxidative stress, oxidative DNA damage, lipid peroxidation, and apoptosis. These results when considered with decreased cortical thickness, activation of cell-cycle arrest pathway, and inhibition of DNA double strand break repair factors led us to conclude to our knowledge for the first time that radiation caused aging-like pathology in cerebral cortical cells and changes after heavy ion radiation were more pronounced than. radiation.
C1 [Suman, Shubhankar; Fornace, Albert J., Jr.; Datta, Kamal] Georgetown Univ, Dept Biochem & Mol & Cell Biol, Med Ctr, Washington, DC 20057 USA.
[Rodriguez, Olga C.; Fornace, Albert J., Jr.; Albanese, Chris; Datta, Kamal] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA.
[Winters, Thomas A.] NIH, Dept Nucl Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA.
[Fornace, Albert J., Jr.] King Abdulaziz Univ, CEGMR, Jeddah 21413, SA, Saudi Arabia.
RP Datta, K (reprint author), Georgetown Univ, Dept Biochem & Mol & Cell Biol, Med Ctr, Washington, DC 20057 USA.
EM kd257@georgetown.edu
FU NASA [NNX07AH70G, NNX09AU95G]; National Cancer Institute (NCI)
[P30CA051008]
FX We are very much thankful to the members of the NASA Space Radiation
Laboratory especially to Drs. Peter Guida and Adam Rusek for their
excellent support in conducting 56Fe radiation exposures. This study is
supported in part by NASA Grant# NNX07AH70G and NNX09AU95G. We also
thank the Histopathology and Tissue Shared Resources at the Lombardi
Comprehensive Cancer Center at Georgetown University for histology
services supported by Award Number P30CA051008 from the National Cancer
Institute (NCI). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 101
TC 16
Z9 17
U1 0
U2 2
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1945-4589
J9 AGING-US
JI Aging-US
PD AUG
PY 2013
VL 5
IS 8
BP 607
EP 622
PG 16
WC Cell Biology
SC Cell Biology
GA 219SM
UT WOS:000324529500008
PM 23928451
ER
PT J
AU Welzel, TM
Graubard, BI
Quraishi, S
Zeuzem, S
Davila, JA
El-Serag, HB
McGlynn, KA
AF Welzel, Tania M.
Graubard, Barry I.
Quraishi, Sabah
Zeuzem, Stefan
Davila, Jessica A.
El-Serag, Hashem B.
McGlynn, Katherine A.
TI Population-Attributable Fractions of Risk Factors for Hepatocellular
Carcinoma in the United States
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Article
ID PRIMARY LIVER-CANCER; C VIRUS-INFECTION; NONALCOHOLIC STEATOHEPATITIS;
DIABETES-MELLITUS; HEPATITIS-B; ALCOHOL; DISEASE; COHORT; EPIDEMIOLOGY;
ASSOCIATION
AB OBJECTIVES: Risk factors for hepatocellular carcinoma (HCC) include hepatitis B and C viruses (HBV, HCV), excessive alcohol consumption, rare genetic disorders and diabetes/obesity. The population attributable fractions (PAF) of these factors, however, have not been investigated in population-based studies in the United States.
METHODS: Persons >= 68 years diagnosed with HCC (n = 6,991) between 1994 and 2007 were identified in the SEER-Medicare database. A 5 % random sample (n = 255,702) of persons residing in SEER locations were selected for comparison. For each risk factor, odds ratios (ORs), 95 % confidence intervals (95 % CI) and PAFs were calculated.
RESULTS: As anticipated, the risk of HCC was increased in relationship to each factor: HCV (OR 39.89, 95 % CI: 36.29-43.84), HBV (OR 11.17, 95 % CI: 9.18-13.59), alcohol-related disorders (OR 4.06, 95 % CI: 3.82-4.32), rare metabolic disorders (OR 3.45, 95 % CI: 2.97-4.02), and diabetes and/or obesity (OR 2.47, 95 % CI: 2.34-2.61). The PAF of all factors combined was 64.5 % (males 65.6 %; females 62.2 %). The PAF was highest among Asians (70.1 %) and lowest among black persons (52.4 %). Among individual factors, diabetes/obesity had the greatest PAF (36.6 %), followed by alcohol-related disorders (23.5%), HCV (22.4%), HBV (6.3%) and rare genetic disorders (3.2%). While diabetes/obesity had the greatest PAF among both males (36.4%) and females (36.7%), alcohol-related disorders had the second greatest PAF among males (27.8%) and HCV the second greatest among females (28.1%). Diabetes/obesity had the greatest PAF among whites (38.9%) and Hispanics (38.1%), while HCV had the greatest PAF among Asians (35.4%) and blacks (34.9%). The second greatest PAF was alcohol-related disorders in whites (25.6%), Hispanics (30.1%) and blacks (and 18.5%) and HBV in Asians (28.5%).
CONCLUSIONS: The dominant risk factors for HCC in the United States among persons = 68 years differ by sex and race/ethnicity. Overall, eliminating diabetes/obesity could reduce the incidence of HCC more than the elimination of any other factor.
C1 [Welzel, Tania M.; Zeuzem, Stefan] Johann Wolfgang Goethe Univ Hosp, Frankfurt, Germany.
[Graubard, Barry I.; Quraishi, Sabah; McGlynn, Katherine A.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD 20852 USA.
[Davila, Jessica A.; El-Serag, Hashem B.] Houston Vet Affairs Med Ctr, Houston, TX USA.
[Davila, Jessica A.; El-Serag, Hashem B.] Baylor Coll Med, Houston, TX 77030 USA.
RP McGlynn, KA (reprint author), NCI, DCEG, NIH, EPS 5022,6120 Execut Blvd, Rockville, MD 20852 USA.
EM mcglynnk@mail.nih.gov
FU Intramural Research Program of the National Cancer Institute, National
Institutes of Health
FX This work was funded by the Intramural Research Program of the National
Cancer Institute, National Institutes of Health.
NR 32
TC 74
Z9 74
U1 0
U2 9
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0002-9270
J9 AM J GASTROENTEROL
JI Am. J. Gastroenterol.
PD AUG
PY 2013
VL 108
IS 8
BP 1314
EP 1321
DI 10.1038/ajg.2013.160
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 222BM
UT WOS:000324704800013
PM 23752878
ER
PT J
AU Roy, A
Jana, M
Corbett, GT
Ramaswamy, S
Kordower, JH
Gonzalez, FJ
Pahan, K
AF Roy, Avik
Jana, Malabendu
Corbett, Grant T.
Ramaswamy, Shilpa
Kordower, Jeffrey H.
Gonzalez, Frank J.
Pahan, Kalipada
TI Regulation of Cyclic AMP Response Element Binding and Hippocampal
Plasticity-Related Genes by Peroxisome Proliferator-Activated Receptor
alpha
SO CELL REPORTS
LA English
DT Article
ID LONG-TERM-MEMORY; PPAR-ALPHA; SYNAPTIC PLASTICITY; ADULT-RAT;
EXPRESSION; PROTEIN; TISSUE; OLIGODENDROCYTES; CONSOLIDATION;
POTENTIATION
AB Peroxisome proliferator-activated receptor alpha (PPAR alpha) is a transcription factor that regulates genes involved in fatty acid catabolism. Here, we provide evidence that PPAR alpha is constitutively expressed in nuclei of hippocampal neurons and, surprisingly, controls calcium influx and the expression of various plasticity-related genes via direct transcriptional regulation of cyclic AMP response element binding (CREB). Accordingly, Ppar alpha-null, but not Ppar beta-null, mice are deficient in CREB and memory-associated proteins and have decreased spatial learning and memory. Small hairpin RNA knockdown of PPAR alpha in the hippocampus suppressed CREB and NR2A, rendering wild-type animals markedly poor in consolidating spatial memory, whereas introduction of PPAR alpha to the hippocampus of Ppar alpha-null mice increased hippocampal CREB and NR2A and improved spatial learning and memory. Through detailed analyses of CREB and NR2A activity, as well as spatial learning and memory in bone marrow chimeric animals lacking PPAR alpha in the CNS, we uncover a mechanism for transcriptional control of Creb and associated plasticity genes by PPAR alpha.
C1 [Roy, Avik; Jana, Malabendu; Corbett, Grant T.; Ramaswamy, Shilpa; Kordower, Jeffrey H.; 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.
RP Pahan, K (reprint author), Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA.
EM kalipada_pahan@rush.edu
FU Alzheimer's Association [IIRG-12-241179]; National Institutes of Health
[AT6681]
FX This study was supported by grants from Alzheimer's Association
(IIRG-12-241179) and National Institutes of Health (AT6681).
NR 32
TC 26
Z9 27
U1 3
U2 11
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 AUG
PY 2013
VL 4
IS 4
BP 724
EP 737
DI 10.1016/j.celrep.2013.07.028
PG 14
WC Cell Biology
SC Cell Biology
GA 216LU
UT WOS:000324285700012
PM 23972989
ER
PT J
AU Wharton, KA
Serpe, M
AF Wharton, Kristi A.
Serpe, Mihaela
TI Fine-tuned shuttles for bone morphogenetic proteins
SO CURRENT OPINION IN GENETICS & DEVELOPMENT
LA English
DT Article
ID REGULATES SYNAPTIC GROWTH; GERMLINE STEM-CELLS; ACTIVITY IN-VITRO;
DROSOPHILA EMBRYO; TGF-BETA; TWISTED GASTRULATION; BMP ACTIVITY;
ACTIVITY GRADIENT; ACTIVATION GRADIENT; SIGNAL-TRANSDUCTION
AB Bone morphogenetic proteins (BMPs) are potent secreted signaling factors that trigger phosphorylation of Smad transcriptional regulators through receptor complex binding at the cell-surface. Resulting changes in target gene expression impact critical cellular responses during development and tissue homeostasis. BMP activity is tightly regulated in time and space by secreted modulators that control BMP extracellular distribution and availability for receptor binding. Such extracellular regulation is key for BMPs to function as morphogens and/or in the formation of morphogen activity gradients. Here, we review shuffling systems utilized to control the distribution of BMP ligands in tissue of various geometries, developing under different temporal constraints. We discuss the biological advantages for employing specific strategies for BMP shuttling and roles of varied ligand forms.
C1 [Wharton, Kristi A.] Brown Univ, Dept Mol Biol Cell Biol & Biochem, Providence, RI 02912 USA.
[Serpe, Mihaela] NICHD, NIH, Program Cellular Regulat & Metab, Bethesda, MD 20892 USA.
RP Serpe, M (reprint author), NICHD, NIH, Program Cellular Regulat & Metab, Bethesda, MD 20892 USA.
EM serpemih@mail.nih.gov
FU Intramural Research Program at NIH, NICHD; NIH [RO1GM068118]; Cali
Family Development Grant from The Center for Research in FOP and Related
Disorders in the Department of Orthopedic Surgery at The Perelman School
of Medicine of The University of Pennsylvania
FX We apologize to authors whose work was not cited due to space
constraints. This work was supported in part by the Intramural Research
Program at NIH, NICHD. KAW acknowledges support from NIH RO1GM068118 and
a Cali Family Development Grant from The Center for Research in FOP and
Related Disorders in the Department of Orthopedic Surgery at The
Perelman School of Medicine of The University of Pennsylvania.
NR 96
TC 7
Z9 7
U1 2
U2 10
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0959-437X
J9 CURR OPIN GENET DEV
JI Curr. Opin. Genet. Dev.
PD AUG
PY 2013
VL 23
IS 4
BP 374
EP 384
DI 10.1016/j.gde.2013.04.012
PG 11
WC Cell Biology; Genetics & Heredity
SC Cell Biology; Genetics & Heredity
GA 217MF
UT WOS:000324362900003
PM 23735641
ER
PT J
AU Daley, WP
Yamada, KM
AF Daley, William P.
Yamada, Kenneth M.
TI ECM-modulated cellular dynamics as a driving force for tissue
morphogenesis
SO CURRENT OPINION IN GENETICS & DEVELOPMENT
LA English
DT Article
ID EPITHELIAL BRANCHING MORPHOGENESIS; EXTRACELLULAR-MATRIX; STEM-CELLS;
CYTOSKELETAL TENSION; BASEMENT-MEMBRANE; FIBRONECTIN; NICHE; RHO;
ARCHITECTURE; ELONGATION
AB The extracellular matrix (ECM) plays diverse regulatory roles throughout development. Coordinate interactions between cells within a tissue and the ECM result in the dynamic remodeling of ECM structure. Both chemical signals and physical forces that result from such microenvironmental remodeling regulate cell behavior that sculpts tissue structure. Here, we review recent discoveries illustrating different ways in which ECM remodeling promotes dynamic cell behavior during tissue morphogenesis. We focus first on new insights that identify localized ECM signaling as a regulator of cell migration, shape, and adhesion during branching morphogenesis. We also review mechanisms by which the ECM and basement membrane can both sculpt and stabilize epithelial tissue structure, using as examples Drosophila egg chamber development and cleft formation in epithelial organs. Finally, we end with an overview of the dynamic mechanisms by which the ECM can regulate stem cell differentiation to contribute to proper tissue morphogenesis.
C1 [Daley, William P.; Yamada, Kenneth M.] Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD USA.
RP Daley, WP (reprint author), Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD USA.
EM daleywp@nih.gov; kenneth.yamada@nih.gov
FU Intramural NIH HHS [ZIA DE000525-22]
NR 54
TC 55
Z9 55
U1 1
U2 18
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0959-437X
J9 CURR OPIN GENET DEV
JI Curr. Opin. Genet. Dev.
PD AUG
PY 2013
VL 23
IS 4
BP 408
EP 414
DI 10.1016/j.gde.2013.05.005
PG 7
WC Cell Biology; Genetics & Heredity
SC Cell Biology; Genetics & Heredity
GA 217MF
UT WOS:000324362900007
PM 23849799
ER
PT J
AU Gao, B
Yang, YZ
AF Gao, Bo
Yang, Yingzi
TI Planar cell polarity in vertebrate limb morphogenesis
SO CURRENT OPINION IN GENETICS & DEVELOPMENT
LA English
DT Article
ID APICAL ECTODERMAL RIDGE; RECESSIVE ROBINOW-SYNDROME; BRACHYDACTYLY
TYPE-B; NEURAL-TUBE CLOSURE; TYROSINE KINASE; ZEBRAFISH GASTRULATION;
CONVERGENT EXTENSION; VENTRICULAR SEPTUM; CHICK LIMB; MOUSE LIMB
AB Studies of the vertebrate limb development have contributed significantly to understanding the fundamental mechanisms underlying growth, patterning, and morphogenesis of a complex multicellular organism. In the limb, well-defined signaling centers interact to coordinate limb growth and patterning along the three axes. Recent analyses of live imaging and mathematical modeling have provided evidence that polarized cell behaviors governed by morphogen gradients play an important role in shaping the limb bud. Furthermore, the Wnt/planar cell polarity (PCP) pathway that controls uniformly polarized cell behaviors in a field of cells has emerged to be critical for directional morphogenesis in the developing limb. Directional information coded in the morphogen gradient may be interpreted by responding cells through regulating the activities of PCP components in a Wnt morphogen dose-dependent manner.
C1 [Gao, Bo; Yang, Yingzi] NHGRI, Bethesda, MD 20892 USA.
RP Yang, YZ (reprint author), NHGRI, Bethesda, MD 20892 USA.
EM yingzi@mail.nih.gov
RI Gao, Bo/F-4688-2013
FU Intramural Research Program of the National Human Genome Institute of
the National Institutes of Health
FX The authors are supported by the Intramural Research Program of the
National Human Genome Institute of the National Institutes of Health.
NR 56
TC 14
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U1 0
U2 15
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0959-437X
J9 CURR OPIN GENET DEV
JI Curr. Opin. Genet. Dev.
PD AUG
PY 2013
VL 23
IS 4
BP 438
EP 444
DI 10.1016/j.gde.2013.05.003
PG 7
WC Cell Biology; Genetics & Heredity
SC Cell Biology; Genetics & Heredity
GA 217MF
UT WOS:000324362900011
PM 23747034
ER
PT J
AU Nugent, AC
Bain, EE
Carlso, PJ
Neumeister, A
Bonne, O
Carson, RE
Eckelman, W
Herscovitch, P
Zarate, CA
Charney, DS
Drevets, WC
AF Nugent, Allison C.
Bain, Earle E.
Carlso, Paul J.
Neumeister, Alexander
Bonne, Omer
Carson, Richard E.
Eckelman, William
Herscovitch, Peter
Zarate, Carlos A., Jr.
Charney, Dennis S.
Drevets, Wayne C.
TI Reduced post-synaptic serotonin type 1A receptor binding in bipolar
depression
SO EUROPEAN NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE 5-HT1A receptor; Positron-emission tomography; Bipolar disorder;
(F-18)FCWAY
ID POSITRON-EMISSION-TOMOGRAPHY; MAJOR DEPRESSION; MINERALOCORTICOID
RECEPTOR; 5-HT1A RECEPTORS; MESSENGER-RNA; PET; DISORDER;
CORTICOSTERONE; SCHIZOPHRENIA; ANTAGONIST
AB Multiple lines of evidence suggest that serotonin type 1A (5-HT1A) receptor dysfunction is involved in the pathophysiology of mood disorders, and that alterations in 5-HT1A receptor function play a role in the mechanisms of antidepressant and mood stabilizer treatment. The literature is in disagreement, however, as to whether 5-HT1A receptor binding abnormalities exist in bipolar disorder (BD). We acquired PET images of 5-HT1A receptor binding in 26 unmedicated BD subjects and 37 healthy controls using [F-18]FCWAY, a highly selective 5-HT1A receptor radio-ligand. The mean 5-HT1A receptor binding potential (BPP) was significantly lower in BD subjects compared to controls in cortical regions where 5-HT1A receptors are expressed post-synaptically, most prominently in the mesiotemporal cortex. Post-hoc assessments involving other receptor specific binding parameters suggested that this difference particularly affected the females with BD. The mean BPP did not differ between groups in the raphe nucleus, however, where 5-HT1A receptors are predominantly expressed pre-synaptically. Across subjects the BPP in the mesiotemporal cortex was inversely correlated with trough plasma cortisol levels, consistent with preclinical literature indicating that hippocampal 5-HT1A receptor expression is inhibited by glucocorticoid receptor stimulation. These findings suggest that 5-HT1A receptor binding is abnormally reduced in BD, and this abnormality may particularly involve the postsynaptic 5-HT1A receptor system of individuals with a tendency toward cortisol hypersecretion. Published by Elsevier B.V.
C1 [Nugent, Allison C.] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD USA.
[Bain, Earle E.] Abbott Labs, Abbott Pk, IL 60064 USA.
[Carlso, Paul J.] Univ Utah, Sch Med, Dept Psychiat, Salt Lake City, UT 84112 USA.
[Neumeister, Alexander] NYU, Sch Med, New York, NY 10016 USA.
[Bonne, Omer] Hadassah Hebrew Univ, Dept Psychiat, Jerusalem, Israel.
[Carson, Richard E.] Yale Univ, Sch Med, Dept Diagnost Radiol, New Haven, CT 06510 USA.
[Eckelman, William] Univ Calif San Diego, San Diego Med Ctr, San Diego, CA 92103 USA.
[Herscovitch, Peter] NIH, Ctr Clin, PET Dept, Bethesda, MD USA.
[Charney, Dennis S.] Mt Sinai Med Ctr, New York, NY 10029 USA.
[Drevets, Wayne C.] Laureate Inst Brain Res, Tulsa, OK USA.
[Drevets, Wayne C.] Univ Oklahoma, Coll Med, Dept Psychiat, Tulsa, OK USA.
[Drevets, Wayne C.] Johnson & Johnson, Titusville, NJ USA.
RP Nugent, AC (reprint author), Sect Neuroimaging Mood Disorders, Expt Therapeut & Pathophysiol Branch, 1 Ctr Dr,Room B1D43S, Bethesda, MD 20892 USA.
EM nugenta@mail.nih.gov
RI Carson, Richard/H-3250-2011;
OI Carson, Richard/0000-0002-9338-7966; Nugent, Allison/0000-0003-2569-2480
FU Intramural Research Program of the NIMH
FX This research was supported by the Intramural Research Program of the
NIMH, under which the first and senior authors were employed at the time
of all data collection, and under which the first author is currently
employed.
NR 30
TC 9
Z9 9
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0924-977X
J9 EUR NEUROPSYCHOPHARM
JI Eur. Neuropsychopharmacol.
PD AUG
PY 2013
VL 23
IS 8
BP 822
EP 829
DI 10.1016/j.euroneuro.2012.11.005
PG 8
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 220QT
UT WOS:000324602700010
PM 23434290
ER
PT J
AU Badaracco, A
Garaicoechea, L
Matthijnssens, J
Uriarte, EL
Odeon, A
Bilbao, G
Fernandez, F
Parra, GI
Parreno, V
AF Badaracco, A.
Garaicoechea, L.
Matthijnssens, J.
Louge Uriarte, E.
Odeon, A.
Bilbao, G.
Fernandez, F.
Parra, G. I.
Parreno, V.
TI Phylogenetic analyses of typical bovine rotavirus genotypes G6, G10,
P[5] and P[11] circulating in Argentinean beef and dairy herds
SO INFECTION GENETICS AND EVOLUTION
LA English
DT Article
DE Bovine; Rotavirus; Phylogeny; Diarrhea; Typing
ID GROUP-A ROTAVIRUS; MOLECULAR CHARACTERIZATION; SEQUENCE-ANALYSIS; VP7
GENES; P-TYPE; MAXIMUM-LIKELIHOOD; PORCINE ROTAVIRUS; SEROLOGICAL
CHARACTERIZATION; INTERSPECIES TRANSMISSION; GENOMIC CHARACTERIZATION
AB Group A rotavirus (RVA) is one of the main causes of neonatal calf diarrhea worldwide. RVA strains affecting Argentinean cattle mainly possess combinations of the G6, G10, P[5] and P[11] genotypes. To determine RVA diversity among Argentinean cattle, representative bovine RVA strains detected in diarrheic calves were selected from a survey conducted during 1997-2009. The survey covered the main livestock regions of the country from dairy and beef herds. Different phylogenetic approaches were used to investigate the genetic evolution of RVA strains belonging to the prevalent genotypes. The nucleotide phylogenetic tree showed that all genotypes studied could be divided into several lineages. Argentinean bovine RVA strains were distributed across multiple lineages and most of them were distinct from the lineage containing the vaccine strains. Only the aminoacid phylogenetic tree of G6 RVA strains maintained the same lineages as observed at the nucleotide level, whereas a different clustering pattern was observed for the aminoacid phylogenetic trees of G10, P[5] and P[11] suggesting that the strains are more closely related at the aminoacid level than G6 strains. Association between P[5] and G6(IV), prevalent in beef herd, and between P[11] and G6(III) or G10 (VI and V), prevalent in dairy herds, were found. In addition, Argentinean G6(III), G10, P[5] and P[11] bovine RVA strains grouped together with human strains, highlighting their potential for zoonotic transmission. Phylogenetic studies of RVA circulating in animals raised for consumption and in close contact with humans, such as cattle, contribute to a better understanding of the epidemiology of the RVA infection and evolution. (C) 2013 Elsevier B.V. All rights reserved.
C1 [Badaracco, A.; Garaicoechea, L.; Fernandez, F.; Parreno, V.] CICV & A INTA, Inst Virol, Buenos Aires, DF, Argentina.
[Matthijnssens, J.] Univ Leuven, Rega Inst Med Res, Dept Microbiol & Immunol, Lab Clin & Epidemiol Virol, Louvain, Belgium.
[Louge Uriarte, E.; Odeon, A.] INTA Balcarce, Grp Sanidad Anim, Balcarce, Buenos Aires, Argentina.
[Bilbao, G.] UNCPBA, Fac Ciencias Vet, Tandil, Buenos Aires, Argentina.
[Parra, G. I.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Parreno, V (reprint author), CICV & A INTA, Inst Virol, Castelar C 25 1712, Buenos Aires, DF, Argentina.
EM vparreno@cnia.inta.gov.ar
RI Matthijnssens, Jelle/A-6770-2015; Matthijnssens, Jelle/B-8634-2016;
OI Parra, Gabriel/0000-0002-1102-4740
FU CONICET; MinCyT [PICT N 38308]; INTA [SALJU 05, SALJU 320051]; FWO
('Fonds voor Wetenschappelijk Onderzoek') post-doctoral fellowship
FX This work was financed by regional projects SALJU 05 and SALJU 320051 at
the INTA, PICT N 38308 at MinCyT. A.B. was supported by a type II
fellowship of CONICET. VP is a joined researcher, CONICET, Argentina.
J.M was supported by an FWO ('Fonds voor Wetenschappelijk Onderzoek')
post-doctoral fellowship.
NR 70
TC 9
Z9 9
U1 0
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1567-1348
J9 INFECT GENET EVOL
JI Infect. Genet. Evol.
PD AUG
PY 2013
VL 18
BP 18
EP 30
DI 10.1016/j.meegid.2013.04.023
PG 13
WC Infectious Diseases
SC Infectious Diseases
GA 221LR
UT WOS:000324660900004
PM 23624201
ER
PT J
AU Andersson, E
Shao, W
Bontell, I
Cham, F
Cuong, DD
Wondwossen, A
Morris, L
Hunt, G
Sonnerborg, A
Bertagnolio, S
Maldarelli, F
Jordan, MR
AF Andersson, Emmi
Shao, Wei
Bontell, Irene
Cham, Fatim
Do Duy Cuong
Wondwossen, Amogne
Morris, Lynn
Hunt, Gillian
Sonnerborg, Anders
Bertagnolio, Silvia
Maldarelli, Frank
Jordan, Michael R.
TI Evaluation of sequence ambiguities of the HIV-1 pol gene as a method to
identify recent HIV-1 infection in transmitted drug resistance surveys
SO INFECTION GENETICS AND EVOLUTION
LA English
DT Article
DE HIV; Viral diversity; Ambiguity; Incidence; Resistance; Bioinformatics
ID IMMUNODEFICIENCY-VIRUS TYPE-1; SURVEILLANCE; POPULATION; SUBTYPE;
COHORT; IDENTIFICATION; INDIVIDUALS; DIVERSITY; MARKER; BED
AB Identification of recent HIV infection within populations is a public health priority for accurate estimation of HIV incidence rates and transmitted drug resistance at population level. Determining HIV incidence rates by prospective follow-up of HIV-uninfected individuals is challenging and serological assays have important limitations. HIV diversity within an infected host increases with duration of infection. We explore a simple bioinformatics approach to assess viral diversity by determining the percentage of ambiguous base calls in sequences derived from standard genotyping of HIV-1 protease and reverse transcriptase. Sequences from 691 recently infected (<= 1 year) and chronically infected (>1 year) individuals from Sweden, Vietnam and Ethiopia were analyzed for ambiguity. A significant difference (p < 0.0001) in the proportion of ambiguous bases was observed between sequences from individuals with recent and chronic infection in both HIV-1 subtype B and non-B infection, consistent with previous studies. In our analysis, a cutoff of <0.47% ambiguous base calls identified recent infection with a sensitivity and specificity of 88.8% and 74.6% respectively. 1,728 protease and reverse transcriptase sequences from 36 surveys of transmitted HIV drug resistance performed following World Health Organization guidance were analyzed for ambiguity. The 0.47% ambiguity cutoff was applied and survey sequences were classified as likely derived from recently or chronically infected individuals. 71% of patients were classified as likely to have been infected within one year of genotyping but results varied considerably amongst surveys. This bioinformatics approach may provide supporting population-level information to identify recent infection but its application is limited by infection with more than one viral variant, decreasing viral diversity in advanced disease and technical aspects of population based sequencing. Standardization of sequencing techniques and base calling and the addition of other parameters such as CD4 cell count may address some of the technical limitations and increase the usefulness of the approach. (C) 2013 Elsevier B.V. All rights reserved.
C1 [Andersson, Emmi; Sonnerborg, Anders] Karolinska Inst, Dept Lab Med, S-14186 Huddinge, Sweden.
[Shao, Wei] SAIC Frederick Inc, Adv Biomed Comp Ctr, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Bontell, Irene; Sonnerborg, Anders] Karolinska Inst, Dept Med, S-14186 Huddinge, Sweden.
[Cham, Fatim] WHO, Harare, Zimbabwe.
[Do Duy Cuong] Bach Mai Hosp, Dept Infect Dis, Hanoi, Vietnam.
[Wondwossen, Amogne] Univ Addis Ababa, Addis Ababa, Ethiopia.
[Morris, Lynn; Hunt, Gillian] Natl Hlth Lab Serv, Natl Inst Communicable Dis, Ctr HIV & STI, Johannesburg, South Africa.
[Bertagnolio, Silvia] WHO, CH-1211 Geneva, Switzerland.
[Maldarelli, Frank] NCI, Frederick, MD 21701 USA.
[Jordan, Michael R.] Tufts Univ, Sch Med, Boston, MA 02111 USA.
RP Andersson, E (reprint author), Karolinska Univ Hosp, Dept Clin Virol, F68, S-14186 Huddinge, Stockholm, Sweden.
EM emmi.andersson@gmail.com; shaow@mail.-nih.gov; irene.bontell@ki.se;
qualabs@gmail.com; doduy.cuong@gmail.com; wonamogne@yahoo.com;
lynnm@nicd.ac.za; GillianH@nicd.ac.za; Anders.Sonnerborg@-ki.se;
bertagnolios@who.int; fmalli@mail.nih.gov;
mjordan@tuftsmedicalcenter.org
RI Luan, Gan/B-3211-2015;
OI , Lynn/0000-0003-3961-7828
FU EU [246599]; NIH [K23 AIO74423-05]; CFAR [P30AI42853]
FX EU FP7 CHAIN Marie Curie ERG (Global ART #246599), NIH K23 AIO74423-05
(MRJ), CFAR P30AI42853 and by a gift from Christine E. Driscoll O'Neill
and James M. Driscoll, Driscoll-O'Neill Charitable Foundation (MRJ).
NR 35
TC 16
Z9 16
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1567-1348
J9 INFECT GENET EVOL
JI Infect. Genet. Evol.
PD AUG
PY 2013
VL 18
BP 125
EP 131
DI 10.1016/j.meegid.2013.03.050
PG 7
WC Infectious Diseases
SC Infectious Diseases
GA 221LR
UT WOS:000324660900016
PM 23583545
ER
PT J
AU Lam, TTY
Chong, YL
Shi, M
Hon, CC
Li, J
Martin, DP
Tang, JLWT
Mok, CK
Shih, SR
Yip, CW
Jiang, JW
Hui, RKH
Pybus, OG
Holmes, EC
Leung, FCC
AF Lam, Tommy Tsan-Yuk
Chong, Yee Ling
Shi, Mang
Hon, Chung-Chau
Li, Jun
Martin, Darren P.
Tang, Julian Wei-Tze
Mok, Chee-Keng
Shih, Shin-Ru
Yip, Chi-Wai
Jiang, Jingwei
Hui, Raymond Kin-Hei
Pybus, Oliver G.
Holmes, Edward C.
Leung, Frederick Chi-Ching
TI Systematic phylogenetic analysis of influenza A virus reveals many novel
mosaic genome segments
SO INFECTION GENETICS AND EVOLUTION
LA English
DT Article
DE Influenza A virus; Mosaic pattern; Recombination; Mosaic screening
protocol
ID PCR-MEDIATED RECOMBINATION; SOUTHERN CHINA; DNA-SEQUENCES; RNA VIRUSES;
HOMOLOGOUS RECOMBINATION; POSITIVE SELECTION; MOLECULAR CLOCK; H5N1;
EVOLUTION; GENE
AB Recombination plays an important role in shaping the genetic diversity of a number of DNA and RNA viruses. Although some recent studies have reported bioinformatic evidence of mosaic sequences in a variety of influenza A viruses, it remains controversial as to whether these represent bona fide natural recombination events or laboratory artifacts. Importantly, mosaic genome structures can create significant topological incongruence during phylogenetic analyses, which can mislead additional phylogeny-based molecular evolutionary analyses such as molecular clock dating, the detection of selection pressures and phylogeographic inference. As a result, there is a strong need for systematic screenings for mosaic structures within the influenza virus genome database. We used a combination of sequence-based and phylogeny-based methods to identify 388 mosaic influenza genomic segments, of which 332 are previously unreported and are significantly supported by phylogenetic methods. It is impossible, however, to ascertain whether these represent natural recombinants. To facilitate the future identification of recombinants, reference sets of non-recombinant sequences were selected for use in an automatic screening protocol for detecting mosaic sequences. Tests using real and simulated mosaic sequences indicate that our screening protocol is both sensitive (average >90%) and accurate (average >77%) enough to identify a range of different mosaic patterns. The relatively high prevalence of mosaic influenza virus sequences implies that efficient systematic screens, such as that proposed here, should be performed routinely to detect natural recombinant strains, potential laboratory artifacts, and sequencing contaminants either prior to sequences being deposited in GenBank or before they are used for phylogenetic analyses. (C) 2013 Elsevier B.V. All rights reserved.
C1 [Lam, Tommy Tsan-Yuk; Pybus, Oliver G.] Univ Oxford, Dept Zool, Oxford OX1 3PS, England.
[Chong, Yee Ling] Univ Malaysia Sarawak, Fac Resource Sci & Technol, Dept Zool, Sarawak, Malaysia.
[Shi, Mang; Holmes, Edward C.] Univ Sydney, Sch Biol Sci, Sydney Emerging Infect & Biosecur Inst, Sydney, NSW 2006, Australia.
[Shi, Mang; Holmes, Edward C.] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia.
[Hon, Chung-Chau] Inst Pasteur, Unite Biol Cellulaire Parasitisme, Dept Biol Cellulaire & Infect, F-75015 Paris, France.
[Li, Jun; Yip, Chi-Wai; Jiang, Jingwei; Hui, Raymond Kin-Hei; Leung, Frederick Chi-Ching] Univ Hong Kong, Sch Biol Sci, Hong Kong, Hong Kong, Peoples R China.
[Martin, Darren P.] Univ Cape Town, Inst Infect Dis & Mol Med, Computat Biol Grp, ZA-7925 Cape Town, South Africa.
[Tang, Julian Wei-Tze] Univ Alberta, Dept Med Microbiol & Immunol, Edmonton, AB T6G 2M7, Canada.
[Mok, Chee-Keng; Shih, Shin-Ru] Chang Gung Univ, Res Ctr Emerging Viral Infect, Tao Yuan, Taiwan.
[Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Lam, TTY (reprint author), Univ Oxford, Dept Zool, S Parks Rd, Oxford OX1 3PS, England.
EM tylam.tommy@gmail.com
RI Lam, Tommy Tsan-Yuk/D-4837-2012;
OI Pybus, Oliver/0000-0002-8797-2667; Holmes, Edward/0000-0001-9596-3552
FU Newton International Fellowship of Royal Society, UK
FX We gratefully thank the scientists who contributed to the influenza
genome sequencing projects and shared their sequences. We acknowledge
the support of HPCPOWER projects for providing computational service
from Computer Centre in The University of Hong Kong. We also thank
W.K.Kwan and Frankie Cheung (CC, HKU) for their technical assistance.
This study was greatly benefited from discussions that took place at the
'Workshop on Phylogenetics for Infectious Diseases - with a focus on DNA
viruses' (10-14 October 2011) hosted by the Institute of Mathematical
Sciences, National University of Singapore. Till is supported by Newton
International Fellowship of Royal Society, UK.
NR 56
TC 14
Z9 14
U1 1
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1567-1348
J9 INFECT GENET EVOL
JI Infect. Genet. Evol.
PD AUG
PY 2013
VL 18
BP 367
EP 378
DI 10.1016/j.meegid.2013.03.015
PG 12
WC Infectious Diseases
SC Infectious Diseases
GA 221LR
UT WOS:000324660900048
PM 23548803
ER
PT J
AU Duvesh, R
Verma, A
Venkatesh, R
Kavitha, S
Ramulu, PY
Wojciechowski, R
Sundaresan, P
AF Duvesh, Roopam
Verma, Anshuman
Venkatesh, Rengaraj
Kavitha, Srinivasan
Ramulu, Pradeep Y.
Wojciechowski, Robert
Sundaresan, Periasamy
TI Association Study in a South Indian Population Supports rs1015213 as a
Risk Factor for Primary Angle Closure
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE PACG; PCMTD1-ST18; South India
ID GLAUCOMA; WORLDWIDE; CHINA; GENE; ST18; EYE
AB PURPOSE. Three loci defined by single nucleotide polymorphisms (SNPs) rs11024102 in PLEKHA7, rs3753841 in COL11A1, and rs1015213 between the PCMTD1 and ST18 genes, recently have been associated with primary angle closure glaucoma (PACG). We explored the genetic association of these SNPs with subtypes of primary angle closure in a South Indian population.
METHODS. The study included three case definitions: primary angle closure/primary angle closure glaucoma (PAC/PACG, N = 180); primary angle closure suspect (PACS, N 171), and a combined any-angle closure group. Controls consisted of 411 individuals from South India. Genotyping for all three SNPs was performed using the TaqMan allelic discrimination assay. Genetic association was estimated using a chi(2) test statistics and logistic regression.
RESULTS. Among the three studied SNPs, significant genetic association was identified for rs1015213 in the PAC/PACG (P = 0.002) and any-angle closure (P = 0.003) analyses. However, no significant genetic association was seen when in PACS subjects (P = 0.052). SNPs rs3753841 and rs11024102 showed no evidence of genetic association with angle-closure phenotypes (P > 0.05) in South Indian participants.
CONCLUSIONS. In our study, rs1015213 (located in the intergenic region between PCMTD1 and ST18) was associated significantly with PAC/PACG, confirming prior reports of an association between this region and angle closure glaucoma. Further work with a larger sample size is necessary to confirm the importance of COL11A1 and PLEKHA7 in the pathogenesis of glaucoma.
C1 [Duvesh, Roopam; Verma, Anshuman; Sundaresan, Periasamy] Aravind Med Res Fdn, Dept Genet, Madurai, Tamil Nadu, India.
[Venkatesh, Rengaraj; Kavitha, Srinivasan] Aravind Eye Hosp, Glaucoma Clin, Pondicherry, India.
[Ramulu, Pradeep Y.] Johns Hopkins Univ Hosp, Glaucoma Div, Baltimore, MD 21287 USA.
[Wojciechowski, Robert] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Wojciechowski, Robert] NHGRI, Inherited Dis Res Branch, Baltimore, MD USA.
[Wojciechowski, Robert] Johns Hopkins Sch Med, Wilmer Eye Inst, Baltimore, MD USA.
RP Sundaresan, P (reprint author), Aravind Eye Hosp, Aravind Med Res Fdn, Dept Genet, 1 Anna Nagar, Madurai 625020, Tamil Nadu, India.
EM sundar@aravind.org
OI Wojciechowski, Robert/0000-0002-9593-4652
FU Aravind Eye Care System; National Human Genome Research Institute;
National Eye Institute [1K08EY022943]
FX Supported by Research to Prevent Blindness (RPB), a Wilmer Pooled
Professorial grant, the Aravind Eye Care System, and intramural funds of
the National Human Genome Research Institute, and by National Eye
Institute Grant 1K08EY022943 (RW).
NR 22
TC 7
Z9 8
U1 0
U2 1
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD AUG
PY 2013
VL 54
IS 8
BP 5624
EP 5628
DI 10.1167/iovs.13-12186
PG 5
WC Ophthalmology
SC Ophthalmology
GA 228EA
UT WOS:000325167200061
PM 23847314
ER
PT J
AU Prasad, V
Vandross, A
Toomey, C
Cheung, M
Rho, J
Quinn, S
Chacko, SJ
Borkar, D
Gall, V
Selvaraj, S
Ho, N
Cifu, A
AF Prasad, Vinay
Vandross, Andrae
Toomey, Caitlin
Cheung, Michael
Rho, Jason
Quinn, Steven
Chacko, Satish Jacob
Borkar, Durga
Gall, Victor
Selvaraj, Senthil
Ho, Nancy
Cifu, Adam
TI A Decade of Reversal: An Analysis of 146 Contradicted Medical Practices
SO MAYO CLINIC PROCEEDINGS
LA English
DT Article
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; ESTROGEN PLUS PROGESTIN; PREIMPLANTATION
GENETIC DIAGNOSIS; RANDOMIZED CONTROLLED-TRIAL; CORONARY-HEART-DISEASE;
HIGH-DOSE CHEMOTHERAPY; RISK BREAST-CANCER; QUALITY-OF-LIFE;
CARDIAC-SURGERY; DEVELOPMENTAL OUTCOMES
AB Objective: To identify medical practices that offer no net benefits.
Methods: We reviewed all original articles published in 10 years (2001-2010) in one high-impact journal. Articles were classified on the basis of whether they addressed a medical practice, whether they tested a new or existing therapy, and whether results were positive or negative. Articles were then classified as 1 of 4 types: replacement, when a new practice surpasses standard of care; back to the drawing board, when a new practice is no better than current practice; reaffirmation, when an existing practice is found to be better than a lesser standard; and reversal, when an existing practice is found to be no better than a lesser therapy. This study was conducted from August 1, 2011, through October 31, 2012.
Results: We reviewed 2044 original articles, 1344 of which concerned a medical practice. Of these, 981 articles (73.0%) examined a new medical practice, whereas 363 (27.0%) tested an established practice. A total of 947 studies (70.5%) had positive findings, whereas 397 (29.5%) reached a negative conclusion. A total of 756 articles addressing a medical practice constituted replacement, 165 were back to the drawing board, 146 were medical reversals, 138 were reaffirmations, and 139 were inconclusive. Of the 363 articles testing standard of care, 146 (40.2%) reversed that practice, whereas 138 (38.0%) reaffirmed it.
Conclusion: The reversal of established medical practice is common and occurs across all classes of medical practice. This investigation sheds light on low-value practices and patterns of medical research. Published by Elsevier Inc on behalf of Mayo Foundation for Medical Education and Research
C1 [Prasad, Vinay] NCI, NIH, Bethesda, MD 20892 USA.
[Vandross, Andrae] Yale Univ, Dept Med, New Haven, CT 06520 USA.
[Toomey, Caitlin; Rho, Jason; Chacko, Satish Jacob] Northwestern Univ, Dept Med, Chicago, IL 60611 USA.
[Borkar, Durga; Selvaraj, Senthil] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Cheung, Michael] Lankenau Med Ctr, Dept Med, Philadelphia, PA USA.
[Quinn, Steven] George Washington Univ, Dept Med, Washington, DC USA.
[Gall, Victor] George Washington Univ, Dept Surg, Washington, DC USA.
[Ho, Nancy] Univ Maryland, Dept Med, Baltimore, MD 21201 USA.
[Cifu, Adam] Univ Chicago, Dept Med, Chicago, IL 60637 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 90
TC 99
Z9 100
U1 2
U2 16
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0025-6196
J9 MAYO CLIN PROC
JI Mayo Clin. Proc.
PD AUG
PY 2013
VL 88
IS 8
BP 790
EP 798
DI 10.1016/j.mayocp.2013.05.012
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 217CE
UT WOS:000324333400008
PM 23871230
ER
PT J
AU Daugirdas, JT
Leypoldt, JK
Akonur, A
Greene, T
Depner, TA
AF Daugirdas, John T.
Leypoldt, John Ken
Akonur, Alp
Greene, Tom
Depner, Thomas A.
CA FHN Trial Grp
TI Improved equation for estimating single-pool Kt/V at higher dialysis
frequencies
SO NEPHROLOGY DIALYSIS TRANSPLANTATION
LA English
DT Article
ID HEMODIALYSIS; UREA
AB Rationale. To measure adequacy in patients dialyzed other than three times per week, guidelines recommend the use of 'standard' Kt/V, which commonly is estimated from treatment Kt/V, time and frequency; however, the accuracy of equations that predict treatment Kt/V in patients being dialyzed other than three times per week has not been evaluated.
Methods. In patients enrolled in the Frequent Hemodialysis Network (FHN) Daily and Nocturnal Trials who were being dialyzed three, four or six times per week, we tested the accuracy of the following Kt/V prediction equation: Kt/V = -ln(R - GFAC x T_hours) + (4-3.5 x R) x 0.55 x weight loss/V, where R = post-dialysis/pre-dialysis blood urea nitrogen and GFAC, originally set to 0.008 for a 3/week schedule (Daugirdas, J Am Soc Nephrol 1993), is a factor that adjusts for urea generation.
Results. With the above equation, there was <0.1% mean error in predicted treatment Kt/V for 3/week patients, but mean errors were -5, -9 and -13% for the 6/week daily, 4/week nocturnal and 6/week nocturnal patients. Modeling simulations were performed to optimize the GFAC term for dialysis schedule and length of the preceding interdialysis interval (PIDI). After substituting schedule-and interval-optimized GFAC terms, the treatment Kt/V prediction errors were reduced to -0.81, +0.1 and -1.3% for the three frequent dialysis schedules tested.
Conclusion. For frequent dialysis schedules, the urea generation factor (GFAC) of one commonly used Kt/V prediction equation should be adjusted based on length in days of the PIDI and number of treatments per week.
C1 [Daugirdas, John T.] Univ Illinois, Dept Med, Chicago, IL 60680 USA.
[Leypoldt, John Ken; Akonur, Alp] Baxter Healthcare Corp, Mcgaw Pk, IL USA.
[Greene, Tom] Univ Utah, Dept Med, Salt Lake City, UT 84112 USA.
[Depner, Thomas A.] Univ Calif Davis, Dept Med, Davis, CA 95616 USA.
[FHN Trial Grp] NIDDKD, Bethesda, MD USA.
RP Daugirdas, JT (reprint author), Univ Illinois, Dept Med, Chicago, IL 60680 USA.
EM jtdaugir@uic.edu
FU National Institutes of Health (NIH), National Institutes of Diabetes and
Digestive and Kidney Diseases; Center for Medicare and Medical Services;
NIH Research Foundation; DaVita; DCI; Fresenius Medical Care; Renal
Advantage; Renal Research Institute; Satellite Healthcare
FX Supported by the National Institutes of Health (NIH), National
Institutes of Diabetes and Digestive and Kidney Diseases, the Center for
Medicare and Medical Services and the NIH Research Foundation.
Contributors to the NIH Foundation in support of the FHN trials included
Amgen, Baxter Healthcare Corporation and Dialysis Clinics, Inc. (DCI).
Additional support was provided by DaVita, DCI, Fresenius Medical Care,
Renal Advantage, Renal Research Institute and Satellite Healthcare. A
list of members of the FHN Trial Group for each study has been
published. See references 12 and 13.
NR 13
TC 10
Z9 11
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0931-0509
J9 NEPHROL DIAL TRANSPL
JI Nephrol. Dial. Transplant.
PD AUG
PY 2013
VL 28
IS 8
BP 2156
EP 2160
DI 10.1093/ndt/gfs115
PG 6
WC Transplantation; Urology & Nephrology
SC Transplantation; Urology & Nephrology
GA 219FC
UT WOS:000324490500031
PM 22561585
ER
PT J
AU Peremyslov, VV
Morgun, EA
Kurth, EG
Makarova, KS
Koonin, EV
Dolja, VV
AF Peremyslov, Valera V.
Morgun, Eva A.
Kurth, Elizabeth G.
Makarova, Kira S.
Koonin, Eugene V.
Dolja, Valerian V.
TI Identification of Myosin XI Receptors in Arabidopsis Defines a Distinct
Class of Transport Vesicles
SO PLANT CELL
LA English
DT Article
ID ENDOPLASMIC-RETICULUM MOTILITY; PROTEIN BODY FORMATION; F-ACTIN
ORGANIZATION; PLANT-CELLS; ROOT HAIR; BREFELDIN-A; TERMINAL DOMAIN;
GOLGI STACKS; MEMBRANE; TRAFFICKING
AB To characterize the mechanism through which myosin XI-K attaches to its principal endomembrane cargo, a yeast two-hybrid library of Arabidopsis thaliana cDNAs was screened using the myosin cargo binding domain as bait. This screen identified two previously uncharacterized transmembrane proteins (hereinafter myosin binding proteins or MyoB1/2) that share a myosin binding, conserved domain of unknown function 593 (DUF593). Additional screens revealed that MyoB1/2 also bind myosin XI-1, whereas myosin XI-I interacts with the distantly related MyoB7. The in vivo interactions of MyoB1/2 with myosin XI-K were confirmed by immunoprecipitation and colocalization analyses. In epidermal cells, the yellow fluorescent protein-tagged MyoB1/2 localize to vesicles that traffic in a myosin XI-dependent manner. Similar to myosin XI-K, MyoB1/2 accumulate in the tip-growing domain of elongating root hairs. Gene knockout analysis demonstrated that functional cooperation between myosin XI-K and MyoB proteins is required for proper plant development. Unexpectedly, the MyoB1-containing vesicles did not correspond to brefeldin A-sensitive Golgi and post-Golgi or prevacuolar compartments and did not colocalize with known exocytic or endosomal compartments. Phylogenomic analysis suggests that DUF593 emerged in primitive land plants and founded a multigene family that is conserved in all flowering plants. Collectively, these findings indicate that MyoB are membrane-anchored myosin receptors that define a distinct, plant-specific transport vesicle compartment.
C1 [Peremyslov, Valera V.; Morgun, Eva A.; Kurth, Elizabeth G.; Dolja, Valerian V.] Oregon State Univ, Dept Bot & Plant Pathol, Corvallis, OR 97331 USA.
[Peremyslov, Valera V.; Morgun, Eva A.; Kurth, Elizabeth G.; Dolja, Valerian V.] Oregon State Univ, Ctr Genome Res & Biocomp, Corvallis, OR 97331 USA.
[Morgun, Eva A.] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA.
[Makarova, Kira S.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Dolja, VV (reprint author), Oregon State Univ, Dept Bot & Plant Pathol, Corvallis, OR 97331 USA.
EM doljav@science.oregonstate.edu
FU National Institutes of Health [R01 GM087658]; U.S. Department of Health
and Human Services
FX We thank David Taylor and Valerie Fraser for excellent technical
assistance. The initial stage of this work was supported by National
Institutes of Health Award R01 GM087658 to V.V.D. K.S. M and E.V.K. are
supported by intramural funds of the U.S. Department of Health and Human
Services (to the National Library of Medicine).
NR 74
TC 26
Z9 33
U1 0
U2 20
PU AMER SOC PLANT BIOLOGISTS
PI ROCKVILLE
PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA
SN 1040-4651
J9 PLANT CELL
JI Plant Cell
PD AUG
PY 2013
VL 25
IS 8
BP 3022
EP 3038
DI 10.1105/tpc.113.113704
PG 17
WC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology
SC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology
GA 224VX
UT WOS:000324920500023
PM 23995081
ER
PT J
AU Ikebe, E
Kawaguchi, A
Tezuka, K
Taguchi, S
Hirose, S
Matsumoto, T
Mitsui, T
Senba, K
Nishizono, A
Hori, M
Hasegawa, H
Yamada, Y
Ueno, T
Tanaka, Y
Sawa, H
Hall, W
Minami, Y
Jeang, KT
Ogata, M
Morishita, K
Hasegawa, H
Fujisawa, J
Iha, H
AF Ikebe, E.
Kawaguchi, A.
Tezuka, K.
Taguchi, S.
Hirose, S.
Matsumoto, T.
Mitsui, T.
Senba, K.
Nishizono, A.
Hori, M.
Hasegawa, H.
Yamada, Y.
Ueno, T.
Tanaka, Y.
Sawa, H.
Hall, W.
Minami, Y.
Jeang, K. T.
Ogata, M.
Morishita, K.
Hasegawa, H.
Fujisawa, J.
Iha, H.
TI Oral administration of an HSP90 inhibitor, 17-DMAG, intervenes
tumor-cell infiltration into multiple organs and improves survival
period for ATL model mice
SO BLOOD CANCER JOURNAL
LA English
DT Article
DE 17-DMAG; molecular chaperon; Tax; ATL; apoptosis; transgenic model
ID NF-KAPPA-B; VIRUS TYPE-1 TAX; BINDING-SITE; IKK-ALPHA;
LEUKEMIA-LYMPHOMA; NEMO/IKK-GAMMA; KINASE COMPLEX; TNF-ALPHA; IN-VIVO;
ACTIVATION
AB In the peripheral blood leukocytes (PBLs) from the carriers of the human T-lymphotropic virus type-1 (HTLV-1) or the patients with adult T-cell leukemia (ATL), nuclear factor kappaB (NF-kappa B)-mediated antiapoptotic signals are constitutively activated primarily by the HTLV-1-encoded oncoprotein Tax. Tax interacts with the I kappa B kinase regulatory subunit NEMO (NF-kappa B essential modulator) to activate NF-kappa B, and this interaction is maintained in part by a molecular chaperone, heat-shock protein 90 (HSP90), and its co-chaperone cell division cycle 37 (CDC37). The antibiotic geldanamycin (GA) inhibits HSP90's ATP binding for its proper interaction with client proteins. Administration of a novel water-soluble and less toxic GA derivative, 17-dimethylaminoethylamino-17-demethoxygeldanamycin hydrochloride (17-DMAG), to Tax-expressing ATL-transformed cell lines, C8166 and MT4, induced significant degradation of Tax. 17-DMAG also facilitated growth arrest and cellular apoptosis to C8166 and MT4 and other ATL cell lines, although this treatment has no apparent effects on normal PBLs. 17-DMAG also downregulated Tax-mediated intracellular signals including the activation of NF-kappa B, activator protein 1 or HTLV-1 long terminal repeat in Tax-transfected HEK293 cells. Oral administration of 17-DMAG to ATL model mice xenografted with lymphomatous transgenic Lck-Tax (Lck proximal promoter-driven Tax transgene) cells or HTLV-1-producing tumor cells dramatically attenuated aggressive infiltration into multiple organs, inhibited de novo viral production and improved survival period. These observations identified 17-DMAG as a promising candidate for the prevention of ATL progression.
C1 [Ikebe, E.; Taguchi, S.; Hirose, S.; Matsumoto, T.; Mitsui, T.; Senba, K.; Nishizono, A.; Iha, H.] Oita Univ, Fac Med, Dept Infect Dis, Yufu, Japan.
[Kawaguchi, A.; Hasegawa, H.] Natl Inst Infect Dis, Dept Pathol, Musashimurayama, Japan.
[Kawaguchi, A.; Sawa, H.] Hokkaido Univ, Dept Mol Pathobiol, 21st Century COE Program Zoonosis Control, Res Ctr Zoonosis Control, Sapporo, Hokkaido, Japan.
[Tezuka, K.; Ueno, T.; Fujisawa, J.] Kansai Med Univ, Dept Microbiol, Moriguchi, Osaka 570, Japan.
[Hori, M.] Ibaraki Cent Hosp, Dept Hematol, Kasama, Ibaraki, Japan.
[Hasegawa, H.; Yamada, Y.] Nagasaki Univ, Grad Sch Biomed Sci, Dept Lab Med, Nagasaki 852, Japan.
[Tanaka, Y.] Univ Ryukyus, Grad Sch Med, Dept Immunol, Nishihara, Okinawa 90301, Japan.
[Hall, W.] Univ Coll Dublin, Dept Med Microbiol, Ctr Res Infect Dis, Conway Inst Biomol & Biomed Res, Dublin 2, Ireland.
[Minami, Y.] Maebashi Inst Technol, Dept Biotechnol, Maebashi, Gumma, Japan.
[Jeang, K. T.] NIAID, Mol Virol Sect, Mol Microbiol Lab, Bethesda, MD 20892 USA.
[Ogata, M.] Oita Univ, Dept Hematol, Fac Med, Yufu, Japan.
[Morishita, K.] Miyazaki Univ, Fac Med, Dept Med Sci, Div Tumor & Cellular Biochem, Miyazaki, Japan.
RP Iha, H (reprint author), Oita Univ, Fac Med, Dept Infect Dis, 1-1 Idaigaoka, Oita 8795593, Japan.
EM hiha@oita-u.ac.jp
RI Sawa, Hirofumi/F-6954-2012;
OI Ogata, Masao/0000-0002-4896-5878; Iha, Hidekatsu/0000-0002-0999-5636
FU Ministry of Education, Culture, Sports, Science and Technology; Ministry
of Health, Labor and Welfare; Ministry of Economy, Trade and Industry;
Japan Science and Technology Agency; Okinawa Science and Technology
Promotion Center; Miyazaki Prefectural Industrial Support Foundation
FX We are indebted to Dr Herbert C Morse III for his helpful discussion and
comments. We thank Mr T Kawashima and Ms Y Itoh for technical assistance
and Drs K Terasawa, C Pique and K Nagata for providing plasmid DNAs. EI
was a research fellow of the Okinawa Science and Technology Promotion
Center. This study was supported in part by grants from the Ministry of
Education, Culture, Sports, Science and Technology; the Ministry of
Health, Labor and Welfare; the Ministry of Economy, Trade and Industry;
Japan Science and Technology Agency; Okinawa Science and Technology
Promotion Center; and Miyazaki Prefectural Industrial Support
Foundation.
NR 53
TC 10
Z9 10
U1 1
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2044-5385
J9 BLOOD CANCER J
JI Blood Cancer J.
PD AUG
PY 2013
VL 3
AR UNSP e132
DI 10.1038/bcj.2013.30
PG 10
WC Oncology
SC Oncology
GA 214XK
UT WOS:000324171500004
PM 23955587
ER
PT J
AU Steel, C
Golden, A
Kubofcik, J
Larue, N
de los Santos, T
Domingo, GJ
Nutman, TB
AF Steel, Cathy
Golden, Allison
Kubofcik, Joseph
LaRue, Nicole
de los Santos, Tala
Domingo, Gonzalo J.
Nutman, Thomas B.
TI Rapid Wuchereria bancrofti-Specific Antigen Wb123-Based IgG4
Immunoassays as Tools for Surveillance following Mass Drug
Administration Programs on Lymphatic Filariasis
SO CLINICAL AND VACCINE IMMUNOLOGY
LA English
DT Article
ID ANTIFILARIAL ANTIBODIES; DIETHYLCARBAMAZINE; ALBENDAZOLE; INFECTION;
CHILDREN; WB123; ASSAY; HAITI
AB The Global Programme to Eliminate Lymphatic Filariasis has an urgent need for rapid assays to detect ongoing transmission of lymphatic filariasis (LF) following multiple rounds of mass drug administration (MDA). Current WHO guidelines support using the antigen card immunochromatographic test (ICT), which detects active filarial infection but does not detect early exposure to LF. Recent studies found that antibody-based assays better serve this function. In the present study, two tests, a rapid IgG4 enzyme-linked immunosorbent assay (ELISA) and a lateral-flow strip immunoassay, were developed based on the highly sensitive and specific Wuchereria bancrofti antigen Wb123. A comparison of W. bancrofti-infected and -uninfected patients (with or without other helminth infections) demonstrated that both tests had high sensitivities and specificities (93 and 97% [ELISA] and 92 and 96% [strips], respectively). When the W. bancrofti-uninfected group was separated into those with other filarial/helminth infections (i.e., onchocerciasis, loiasis, and strongyloidiasis) and those who were parasite uninfected, the specificities of the assays varied between 91 and 100%. In addition, the geometric mean response by ELISA of W. bancrofti-infected patients was significantly higher than the response of those without W. bancrofti infection (P < 0.0001). Furthermore, the Wb123 ELISA and the lateral-flow strips had high positive and negative predictive values, giving valuable information on the size of survey population needed to be reasonably certain whether or not transmission is ongoing. These highly sensitive and specific IgG4 tests to the W. bancrofti Wb123 protein give every indication that they will serve as useful tools for post-MDA monitoring.
C1 [Steel, Cathy; Kubofcik, Joseph; Nutman, Thomas B.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD USA.
[Golden, Allison; LaRue, Nicole; de los Santos, Tala; Domingo, Gonzalo J.] PATH, Diagnost Grp, Seattle, WA USA.
RP Nutman, TB (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD USA.
EM tnutman@niaid.nih.gov
FU NIH, NIAID
FX This research was supported by the Intramural Research Program of the
NIH, NIAID.
NR 17
TC 10
Z9 10
U1 1
U2 9
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 1556-6811
J9 CLIN VACCINE IMMUNOL
JI Clin. Vaccine Immunol.
PD AUG
PY 2013
VL 20
IS 8
BP 1155
EP 1161
DI 10.1128/CVI.00252-13
PG 7
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 190CY
UT WOS:000322316800008
PM 23740923
ER
PT J
AU Lucero, CM
Junecko, BF
Klamar, CR
Sciullo, LA
Berendam, SJ
Cillo, AR
Qin, SL
Sui, YJ
Sanghavi, S
Murphey-Corb, MA
Reinhart, TA
AF Lucero, Carissa M.
Junecko, Beth Fallert
Klamar, Cynthia R.
Sciullo, Lauren A.
Berendam, Stella J.
Cillo, Anthony R.
Qin, Shulin
Sui, Yongjun
Sanghavi, Sonali
Murphey-Corb, Michael A.
Reinhart, Todd A.
TI Macaque Paneth Cells Express Lymphoid Chemokine CXCL13 and Other
Antimicrobial Peptides Not Previously Described as Expressed in
Intestinal Crypts
SO CLINICAL AND VACCINE IMMUNOLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS-INFECTION; FOLLICULAR DENDRITIC CELLS; CHAIN
FATTY-ACIDS; HIV-INFECTION; T-CELLS; B-CELLS; CYNOMOLGUS MACAQUES;
CATHELICIDIN LL-37; ALTERED EXPRESSION; GERMINAL-CENTERS
AB CXCL13 is a constitutively expressed chemokine that controls migration of immune cells to lymphoid follicles. Previously, we found CXCL13 mRNA levels increased in rhesus macaque spleen tissues during AIDS. This led us to examine the levels and locations of CXCL13 by detailed in situ methods in cynomolgus macaque lymphoid and intestinal tissues. Our results revealed that there were distinct localization patterns of CXCL13 mRNA compared to protein in germinal centers. These patterns shifted during the course of simian immunodeficiency virus (SIV) infection, with increased mRNA expression within and around follicles during AIDS compared to uninfected or acutely infected animals. Unexpectedly, CXCL13 expression was also found in abundance in Paneth cells in crypts throughout the small intestine. Therefore, we expanded our analyses to include chemokines and antimicrobial peptides (AMPs) not previously demonstrated to be expressed by Paneth cells in intestinal tissues. We examined the expression patterns of multiple chemokines, including CCL25, as well as alpha-defensin 6 (DEFA6), beta-defensin 2 (BDEF2), rhesus theta-defensin 1 (RTD-1), and Reg3 gamma in situ in intestinal tissues. Of the 10 chemokines examined, CXCL13 was unique in its expression by Paneth cells. BDEF2, RTD-1, and Reg3 gamma were also expressed by Paneth cells. BDEF2 and RTD-1 previously have not been shown to be expressed by Paneth cells. These findings expand our understanding of mucosal immunology, innate antimicrobial defenses, homeostatic chemokine function, and host protective mechanisms against microbial translocation.
C1 [Lucero, Carissa M.; Junecko, Beth Fallert; Klamar, Cynthia R.; Sciullo, Lauren A.; Berendam, Stella J.; Qin, Shulin; Reinhart, Todd A.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Infect Dis & Microbiol, Pittsburgh, PA 15261 USA.
[Cillo, Anthony R.; Murphey-Corb, Michael A.] Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA USA.
[Sui, Yongjun] NCI, Bethesda, MD 20892 USA.
[Sanghavi, Sonali] King Edward Mem Hosp & Res Ctr, Pune, Maharashtra, India.
RP Reinhart, TA (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Infect Dis & Microbiol, Pittsburgh, PA 15261 USA.
EM reinhar@pitt.edu
FU NIH [AI060422, AI90825]; K. Leroy Irvis Scholarship program at the
University of Pittsburgh; NIH from the NIAID [T32 AI065380]
FX This project was supported by NIH grants AI060422 (T. A. R.) and AI90825
(M. M. C.), the K. Leroy Irvis Scholarship program at the University of
Pittsburgh (C. M. L.), and NIH T32 AI065380 (Pitt AIDS Research Training
Program) from the NIAID.
NR 47
TC 3
Z9 3
U1 1
U2 11
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 1556-6811
J9 CLIN VACCINE IMMUNOL
JI Clin. Vaccine Immunol.
PD AUG
PY 2013
VL 20
IS 8
BP 1320
EP 1328
DI 10.1128/CVI.00651-12
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 190CY
UT WOS:000322316800029
PM 23803902
ER
PT J
AU Hung, SSC
Wong, RCB
Sharov, AA
Nakatake, Y
Yu, H
Ko, MSH
AF Hung, Sandy S. C.
Wong, Raymond C. B.
Sharov, Alexei A.
Nakatake, Yuhki
Yu, Hong
Ko, Minoru S. H.
TI Repression of Global Protein Synthesis by Eif1a-Like Genes That Are
Expressed Specifically in the Two-Cell Embryos and the Transient
Zscan4-Positive State of Embryonic Stem Cells
SO DNA RESEARCH
LA English
DT Article
DE Eif1a-like genes; global translational repression; embryonic stem cell;
two-cell stage embryo; Zscan4
ID PREIMPLANTATION MOUSE EMBRYO; INITIATION-FACTORS; GENOMIC STABILITY;
DNA-REPLICATION; ES CELLS; PHOSPHORYLATION; ACTIVATION; MITOSIS; ZSCAN4;
TRANSLATION
AB Mouse embryonic stem (ES) cells are prototypical stem cells that remain undifferentiated in culture for long periods, yet maintain the ability to differentiate into essentially all cell types. Previously, we have reported that ES cells oscillate between two distinct states, which can be distinguished by the transient expression of Zscan4 genes originally identified for its specific expression in mouse two-cell stage embryos. Here, we report that the nascent protein synthesis is globally repressed in the Zscan4-positive state of ES cells, which is mediated by the transient expression of newly identified eukaryotic translation initiation factor 1A (Eif1a)-like genes. Eif1a-like genes, clustered on Chromosome 12, show the high sequence similarity to the Eifa1 and consist of 10 genes (Eif1al1 Eif1al10) and 9 pseudogenes (Eif1al-ps1-Eif1al-ps9). The analysis of the expressed sequence tag database showed that Eif1a-like genes are expressed mostly in the two-cell stage mouse embryos. Microarray analyses and quantitative real-time polymerase chain reaction analyses show that Eif1a-like genes are expressed specifically in the Zscan4-positive state of ES cells. These results indicate a novel mechanism to repress protein synthesis by Eif1a-like genes and a unique mode of protein synthesis regulation in ES cells, which undergo a transient and reversible repression of global protein synthesis in the Zscan4-positive state.
C1 [Hung, Sandy S. C.; Wong, Raymond C. B.; Sharov, Alexei A.; Nakatake, Yuhki; Yu, Hong; Ko, Minoru S. H.] NIA, Dev Genom & Aging Sect, Genet Lab, NIH, Baltimore, MD 21224 USA.
[Nakatake, Yuhki; Ko, Minoru S. H.] Keio Univ, Sch Med, Dept Syst Med,Sakaguchi Lab, Shinjuku Ku, Tokyo 1608582, Japan.
RP Ko, MSH (reprint author), NIA, Dev Genom & Aging Sect, Genet Lab, NIH, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA.
EM kom@z7.keio.jp
RI Nakatake, Yuhki/K-5405-2013;
OI Hung, Sandy/0000-0002-7496-7092; Ko, Minoru/0000-0002-3530-3015
FU Intramural Research Program of the NIH, National Institute on Aging
FX This work was in part supported by the Intramural Research Program of
the NIH, National Institute on Aging.
NR 36
TC 10
Z9 10
U1 0
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1340-2838
J9 DNA RES
JI DNA Res.
PD AUG
PY 2013
VL 20
IS 4
BP 391
EP 401
DI 10.1093/dnares/dst018
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA 215PW
UT WOS:000324223800007
PM 23649898
ER
PT J
AU Trnovec, T
Jusko, TA
Sovcikova, E
Lancz, K
Chovancova, J
Patayova, H
Palkovicova, L
Drobna, B
Langer, P
Van den Berg, M
Dedik, L
Wimmerova, S
AF Trnovec, Tomas
Jusko, Todd A.
Sovcikova, Eva
Lancz, Kinga
Chovancova, Jana
Patayova, Henrieta
Palkovicova, L'ubica
Drobna, Beata
Langer, Pavel
Van den Berg, Martin
Dedik, Ladislav
Wimmerova, Sona
TI Relative Effect Potency Estimates of Dioxin-like Activity for Dioxins,
Furans, and Dioxin-like PCBs in Adults Based on Two Thyroid Outcomes
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE dioxin-like polychlorinated biphenyl (DL-PCB); free thyroxine (FT4);
polychlorinated dibenzo-p-dioxins (PCDDs); polychlorinated
dibenzo-p-furans (PCDFs); relative effect potency (REP); thyroid volume;
toxic equivalency factor (TEF)
ID ENVIRONMENTAL CHEMICALS; HORMONE LEVELS; SERUM; ULTRASOUND; EXPOSURE;
HEALTH; VOLUME; POPULATION; PESTICIDES; POLLUTANTS
AB BACKGROUND: Toxic equivalency factors (TEFs) are an important component in the risk assessment of dioxin-like human exposures. At present, this concept is based mainly on in vivo animal experiments using oral dosage. Consequently, the current human TEFs derived from mammalian experiments are applicable only for exposure situations in which oral ingestion occurs. Nevertheless, these "intake" TEFs are commonly-but incorrectly-used by regulatory authorities to calculate "systemic" toxic equivalents (TEQs) based on human blood and tissue concentrations, which are used as biomarkers for either exposure or effect.
OBJECTIVES: We sought to determine relative effect potencies (REPs) for systemic human concentrations of dioxin-like mixture components using thyroid volume or serum free thyroxine (FT4) concentration as the outcomes of interest.
METHODS: We used a benchmark concentration and a regression-based approach to compare the strength of association between each dioxin-like compound and the thyroid end points in 320 adults residing in an organochlorine-polluted area of eastern Slovakia.
RESULTS: REPs calculated from thyroid volume and FT4 were similar. The regression coefficient (beta)-derived REP data from thyroid volume and FT4 level were correlated with the World Health Organization (WHO) TEF values (Spearman r = 0.69, p = 0.01 and r = 0.62, p = 0.03, respectively). The calculated REPs were mostly within the minimum and maximum values for in vivo REPs derived by other investigators.
CONCLUSIONS: Our REPs calculated from thyroid end points realistically reflect human exposure scenarios because they are based on chronic, low-dose human exposures and on biomarkers reflecting body burden. Compared with previous results, our REPs suggest higher sensitivity to the effects of dioxin-like compounds.
C1 [Trnovec, Tomas; Sovcikova, Eva; Lancz, Kinga; Chovancova, Jana; Patayova, Henrieta; Palkovicova, L'ubica; Drobna, Beata; Wimmerova, Sona] Slovak Med Univ, Bratislava 83303, Slovakia.
[Jusko, Todd A.] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Langer, Pavel] Slovak Acad Sci, Inst Expt Endocrinol, Bratislava, Slovakia.
[Van den Berg, Martin] Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands.
[Dedik, Ladislav] Slovak Univ Technol Bratislava, Fac Mech Engn, Bratislava, Slovakia.
RP Trnovec, T (reprint author), Slovak Med Univ, Limbova 12, Bratislava 83303, Slovakia.
EM tomas.trnovec@szu.sk
FU European Union (EU) [QLK4-CT-2000-00488, FP7-ENV-226694]; Competence
Center for SMART Technologies for Electronics and Informatics Systems
and Services [ITMS 26240220072]; Research & Development Operational
Programme from the ERDF and Scientific Grant Agency VEGA (Bratislava,
Slovakia) [1/0120/12]; Intramural Research Program of the National
Institute of Environmental Health Sciences, National Institutes of
Health
FX This work was supported by the European Union (EU) 5th Framework
Programme, project PCBRISK (Evaluating Human Health Risk from Low-dose
and Long-term PCB Exposure; QLK4-CT-2000-00488); the EU 7th Framework
Programme project SYSTEQ [The Development, Validation and Implementation
of Human Systemic Toxic Equivalencies (TEQs) as Biomarkers for Dioxin
Like Compounds; grant FP7-ENV-226694]; and the Competence Center for
SMART Technologies for Electronics and Informatics Systems and Services,
ITMS 26240220072, funded by the Research & Development Operational
Programme from the ERDF and Scientific Grant Agency VEGA (Bratislava,
Slovakia), grant 1/0120/12. This research also received support from the
Intramural Research Program of the National Institute of Environmental
Health Sciences, National Institutes of Health.
NR 40
TC 8
Z9 8
U1 2
U2 26
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD AUG
PY 2013
VL 121
IS 8
BP 886
EP 892
DI 10.1289/ehp.1205739
PG 7
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 208WC
UT WOS:000323711700014
PM 23665575
ER
PT J
AU Steenland, K
Zhao, LP
Winquist, A
Parks, C
AF Steenland, Kyle
Zhao, Liping
Winquist, Andrea
Parks, Christine
TI Ulcerative Colitis and Perfluorooctanoic Acid (PFOA) in a Highly Exposed
Population of Community Residents and Workers in the Mid-Ohio Valley
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE autoimmune; inflammatory bowel disease; PFOA; ulcerative colitis
ID INFLAMMATORY-BOWEL-DISEASE; ACTIVATED-RECEPTOR-ALPHA; PERFLUORINATED
COMPOUNDS; AUTOIMMUNE-DISEASES; COHORT MORTALITY; US POPULATION; HEALTH;
GAMMA; MICE; IMMUNOTOXICITY
AB BACKGROUND: Little is known about environmental determinants of auto-immune diseases.
OBJECTIVES: We studied auto-immune diseases in relation to level of exposure to perfluorooctanoic acid (PFOA), which was introduced in the late 1940s and is now ubiquitous in the serum of residents of industrialized countries.
METHODS: In 2008-2011 we interviewed 32,254 U.S. adults with high serum PFOA serum levels (median, 28 ng/mL) associated with drinking contaminated water near a chemical plant. Disease history was assessed retrospectively from 1952 or birth (if later than 1952) until interview. Self-reported history of auto-immune disease was validated via medical records. Cumulative exposure to PFOA was derived from estimates of annual mean serum PFOA levels during follow-up, which were based on plant emissions, residential and work history, and a fate-transport model. Cox regression models were used to estimate associations between quartiles of cumulative PFOA serum levels and the incidence of auto-immune diseases with >= 50 validated cases, including ulcerative colitis (n = 151), Crohn's disease (n = 96), rheumatoid arthritis (n = 346), insulin-dependent diabetes (presumed to be type 1) (n = 160), lupus (n = 75), and multiple sclerosis (n = 98).
RESULTS: The incidence of ulcerative colitis was significantly increased in association with PFOA exposure, with adjusted rate ratios by quartile of exposure of 1.00 (referent), 1.76 (95% CI: 1.04, 2.99), 2.63 (95% CI: 1.56, 4.43), and 2.86 (95% CI: 1.65, 4.96) (p(trend) < 0.0001). A prospective analysis of ulcerative colitis diagnosed after the baseline 2005-2006 survey (n = 29 cases) suggested a positive but non-monotonic trend (p(trend) = 0.21).
DISCUSSION: To our knowledge, this is the first study of associations between this common environmental exposure and auto-immune diseases in humans. We found evidence that PFOA is associated with ulcerative colitis.
C1 [Steenland, Kyle; Zhao, Liping; Winquist, Andrea] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.
[Parks, Christine] NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Steenland, K (reprint author), Emory Univ, Rollins Sch Publ Hlth, 1518 Clifton Rd, Atlanta, GA 30322 USA.
EM nsteenl@emory.edu
FU C8 Class Action Settlement Agreement (Circuit Court of Wood County, West
Virginia); Intramural Program of the National Institute of Environmental
Health Sciences, National Institutes of Health
FX This research was funded by the C8 Class Action Settlement Agreement
(Circuit Court of Wood County, West Virginia) between DuPont and
Plaintiffs, which resulted from releases into drinking water of the
chemical perfluorooctanoic acid (PFOA, or C8). Funds were administered
by an agency that reports to the court. The contribution of C.P. to this
research was supported by the Intramural Program of the National
Institute of Environmental Health Sciences, National Institutes of
Health. Our work and conclusions are independent of either party to the
lawsuit.
NR 38
TC 23
Z9 23
U1 1
U2 25
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD AUG
PY 2013
VL 121
IS 8
BP 900
EP 905
DI 10.1289/ehp.1206449
PG 6
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 208WC
UT WOS:000323711700016
PM 23735465
ER
PT J
AU Hou, LF
Andreotti, G
Baccarelli, AA
Savage, S
Hoppin, JA
Sandler, DP
Barker, J
Zhu, ZZ
Hoxha, M
Dioni, L
Zhang, X
Koutros, S
Freeman, LEB
Alavanja, MC
AF Hou, Lifang
Andreotti, Gabriella
Baccarelli, Andrea A.
Savage, Sharon
Hoppin, Jane A.
Sandler, Dale P.
Barker, Joseph
Zhu, Zhong-Zheng
Hoxha, Mirjam
Dioni, Laura
Zhang, Xiao
Koutros, Stella
Freeman, Laura E. Beane
Alavanja, Michael C.
TI Lifetime Pesticide Use and Telomere Shortening among Male Pesticide
Applicators in the Agricultural Health Study
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE Agricultural Health Study; cancer-free subjects; occupational exposures;
pesticides; telomere length
ID ALACHLOR MANUFACTURING WORKERS; MULTIPLEX QUANTITATIVE PCR;
NON-HODGKIN-LYMPHOMA; CANCER INCIDENCE; OXIDATIVE STRESS; LUNG-CANCER;
IN-VITRO; PERIPHERAL LYMPHOCYTES; BLADDER-CANCER; DNA-DAMAGE
AB BACKGROUND: Telomere length (TL) in surrogate tissues may be influenced by environmental exposures.
OBJECTIVE: We aimed to determine whether lifetime pesticides use is associated with buccal cell TL.
METHODS: We examined buccal cell TL in relation to lifetime use of 48 pesticides for 1,234 cancer-free white male pesticide applicators in the Agricultural Health Study (AHS), a prospective cohort study of 57,310 licensed pesticide applicators. Participants provided detailed information on lifetime use of 50 pesticides at enrollment (1993-1997). Buccal cells were collected from 1999 to 2006. Relative telomere length (RTL) was measured using quantitative real-time polymerase chain reaction. We used linear regression modeling to evaluate the associations between specific pesticides and the logarithm of RTL, adjusting for age at buccal cell collection, state of residence, applicator license type, chewing tobacco use, and total lifetime days of all pesticide use.
RESULTS: The mean RTL for participants decreased significantly in association with increased lifetime days of pesticide use for alachlor (p = 0.002), 2,4-dichlorophenoxyacetic acid (2,4-D; p = 0.004), metolachlor (p = 0.01), trifluralin (p = 0.05), permethrin (for animal application) (p = 0.02), and toxaphene (p = 0.04). A similar pattern of RTL shortening was observed with the metric lifetime intensity-weighted days of pesticide use. For dichlorodiphenyl-trichloroethane (DDT), we observed significant RTL shortening for lifetime intensity-weighted days (p = 0.04), but not for lifetime days of DDT use (p = 0.08). No significant RTL lengthening was observed for any pesticide.
CONCLUSION: Seven pesticides previously associated with cancer risk in the epidemiologic literature were inversely associated with RTL in buccal cell DNA among cancer-free pesticide applicators. Replication of these findings is needed because we cannot rule out chance or fully rule out bias.
C1 [Hou, Lifang; Zhang, Xiao] Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA.
[Hou, Lifang] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA.
[Andreotti, Gabriella; Savage, Sharon; Koutros, Stella; Freeman, Laura E. Beane; Alavanja, Michael C.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Baccarelli, Andrea A.] Harvard Univ, Sch Publ Hlth, Exposure Epidemiol & Risk Program, Boston, MA 02115 USA.
[Hoppin, Jane A.; Sandler, Dale P.] NIEHS, Epidemiol Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Barker, Joseph] IMS, Silver Spring, MD USA.
[Zhu, Zhong-Zheng] Peoples Liberat Army, Dept Oncol, Hosp 113, Ningbo, Zhejiang, Peoples R China.
[Hoxha, Mirjam; Dioni, Laura] Univ Milan, Dept Environm & Occupat Hlth, Ctr Mol & Genet Epidemiol, Milan, Italy.
[Hoxha, Mirjam; Dioni, Laura] Fdn Osped Maggiore Policlin Mangiagalli & Regina, Ist Ricovero & Cura Carattere Sci, Milan, Italy.
RP Alavanja, MC (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Rm 8000, North Bethesda, MD 20892 USA.
EM alavanjm@mail.nih.gov
OI Baccarelli, Andrea/0000-0002-3436-0640; Savage,
Sharon/0000-0001-6006-0740; Sandler, Dale/0000-0002-6776-0018
FU Intramural Research Program of the Division of Cancer Epidemiology and
Genetics, National Cancer Institute [Z01CP0119]; Epidemiology Branch of
the National Institute of Environmental Health Sciences, National
Institutes of Health [Z01ES049030]
FX This research was supported by the Intramural Research Program of the
Division of Cancer Epidemiology and Genetics, National Cancer Institute
(Z01CP0119) and the Epidemiology Branch of the National Institute of
Environmental Health Sciences, National Institutes of Health
(Z01ES049030). J.B. is employed by IMS, Silver Spring, Maryland.
NR 68
TC 12
Z9 12
U1 3
U2 34
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD AUG
PY 2013
VL 121
IS 8
BP 919
EP 924
DI 10.1289/ehp.1206432
PG 6
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 208WC
UT WOS:000323711700019
PM 23774483
ER
PT J
AU Xu, YY
Tokar, EJ
Person, RJ
Orihuela, RG
Ngalame, NNO
Waalkes, MP
AF Xu, Yuanyuan
Tokar, Erik J.
Person, Rachel J.
Orihuela, Ruben G.
Ngalame, Ntube N. O.
Waalkes, Michael P.
TI Recruitment of Normal Stem Cells to an Oncogenic Phenotype by
Noncontiguous Carcinogen-Transformed Epithelia Depends on the
Transforming Carcinogen
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE cadmium; cancer stem cells; inflammatory factors; prostate; stem cells
ID INDUCED MALIGNANT TRANSFORMATION; BREAST-CANCER CELLS; ARSENIC EXPOSURE;
MESENCHYMAL TRANSITION; PROSTATE-CANCER; TGF-BETA; STEM/PROGENITOR;
CADMIUM; METASTASIS; EXPRESSION
AB BACKGROUND: Cancer stem cells (CSCs) drive tumor initiation, progression, and metastasis. The microenvironment is critical to the fate of CSCs. We have found that a normal stem cell (NSC) line from human prostate (WPE-stem) is recruited into CSC-like cells by nearby, but noncontiguous, arsenic-transformed isogenic malignant epithelial cells (MECs).
OBJECTIVE: It is unknown whether this recruitment of NSCs into CSCs by noncontact co-culture is specific to arsenic-transformed MECs. Thus, we used co-culture to examine the effects of neighboring non-contiguous cadmium-transformed MECs (Cd-MECs) and N-methyl-N-nitrosourea-transformed MECs (MNU-MECs) on NSCs.
RESULTS: After 2 weeks of non-contact Cd-MEC co-culture, NSCs showed elevated metallo-proteinase-9 (MMP-9) and MMP-2 secretion, increased invasiveness, increased colony formation, decreased PTEN expression, and formation of aggressive, highly branched duct-like structures from single cells in Matrigel, all characteristics typical of cancer cells. These oncogenic characteristics did not occur in NSCs co-cultured with MNU-MECs. The NSCs co-cultured with Cd-MECs retained self-renewal capacity, as evidenced by multiple passages (>3) of structures formed in Matrigel. Cd-MEC-co-cultured NSCs also showed molecular (increased VIM, SNAIL1, and TWIST1 expression; decreased E-CAD expression) and morphologic evidence of epithelial-to-mesenchymal transition typical for conversion to CSCs. Dysregulated expression of SC-renewal genes, including ABCG2, OCT-4, and WNT-3, also occurred in NSCs during oncogenic transformation induced by non-contact co-culture with Cd-MECs.
CONCLUSIONS: These data indicate that Cd-MECs can recruit nearby NSCs into a CSC-like phenotype, but MNU-MECs do not. Thus, the recruitment of NSCs into CSCs by nearby MECs is dependent on the carcinogen originally used to malignantly transform the MECs.
C1 [Xu, Yuanyuan; Tokar, Erik J.; Person, Rachel J.; Orihuela, Ruben G.; Ngalame, Ntube N. O.; Waalkes, Michael P.] NIEHS, Natl Toxicol Program Lab, Div Natl Toxicol Program, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Waalkes, MP (reprint author), 111 TW Alexander Dr,MD E1-07, Res Triangle Pk, NC 27709 USA.
EM waalkes@niehs.nih.gov
OI ORIHUELA, RUBEN/0000-0001-6718-6194
NR 45
TC 4
Z9 5
U1 1
U2 7
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD AUG
PY 2013
VL 121
IS 8
BP 944
EP 950
DI 10.1289/ehp.1306714
PG 7
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 208WC
UT WOS:000323711700023
PM 23687063
ER
PT J
AU Furey, ML
Zarate, CA
AF Furey, Maura L.
Zarate, Carlos A., Jr.
TI Pulsed Intravenous Administration of Scopolamine Produces Rapid
Antidepressant Effects and Modest Side Effects
SO JOURNAL OF CLINICAL PSYCHIATRY
LA English
DT Editorial Material
ID AFFECTIVE-DISORDERS; CLINICAL-TRIAL; DOUBLE-BLIND; DEPRESSION; PLACEBO;
SUPERSENSITIVITY; BIPERIDEN
C1 [Furey, Maura L.; Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20892 USA.
RP Furey, ML (reprint author), 15K North Dr,Bldg 15K,Rm 201, Bethesda, MD 20892 USA.
EM mfurey@mail.nih.gov
FU Intramural NIH HHS [Z99 MH999999]
NR 20
TC 2
Z9 3
U1 1
U2 6
PU PHYSICIANS POSTGRADUATE PRESS
PI MEMPHIS
PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA
SN 0160-6689
J9 J CLIN PSYCHIAT
JI J. Clin. Psychiatry
PD AUG
PY 2013
VL 74
IS 8
BP 850
EP 851
DI 10.4088/JCP.13ac08584
PG 2
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA 212NI
UT WOS:000323989700011
PM 24021505
ER
PT J
AU Moya, PR
Wendland, JR
Rubenstein, LM
Timpano, KR
Heiman, GA
Tischfield, JA
King, RA
Andrews, AM
Ramamoorthy, S
McMahon, FJ
Murphy, DL
AF Moya, Pablo R.
Wendland, Jens R.
Rubenstein, Liza M.
Timpano, Kiara R.
Heiman, Gary A.
Tischfield, Jay A.
King, Robert A.
Andrews, Anne M.
Ramamoorthy, Samanda
McMahon, Francis J.
Murphy, Dennis L.
TI Common and rare alleles of the serotonin transporter gene, SLC6A4,
associated with Tourette's disorder
SO MOVEMENT DISORDERS
LA English
DT Article
DE SLC6A4; serotonin transporter (SERT); Tourette's; serotonin; 5-HTTLPR;
SERT isoleucine-to-valine substitution (I425V)
ID OBSESSIVE-COMPULSIVE DISORDER; 5-HTTLPR POLYMORPHISM; FUNCTIONAL
VARIANT; REGULATORY REGION; BLOOD SEROTONIN; PROTEIN-KINASE; MULTIPLE
TICS; MICE; SUSCEPTIBILITY; DEPRESSION
AB To evaluate the hypothesis that functionally over-expressing alleles of the serotonin transporter (SERT) gene (solute carrier family 6, member 4, SLC6A4) are present in Tourette's disorder (TD), just as we previously observed in obsessive compulsive disorder (OCD), we evaluated TD probands (N=151) and controls (N=858). We genotyped the refined SERT-linked polymorphic region 5-HTTLPR/rs25531 and the associated rs25532 variant in the SLC6A4 promoter plus the rare coding variant SERT isoleucine-to-valine at position 425 (I425V). The higher expressing 5-HTTLPR/rs25531 L-A allele was more prevalent in TD probands than in controls ((2)=5.75; P=0.017; odds ratio [OR], 1.35); and, in a secondary analysis, surprisingly, it was significantly more frequent in probands who had TD alone than in those who had TD plus OCD (Fisher's exact test; P=0.0006; OR, 2.29). Likewise, the higher expressing L-AC haplotype (5-HTTLPR/rs25531/rs25532) was more frequent in TD probands than in controls (P=0.024; OR, 1.33) and also in the TD alone group versus the TD plus OCD group (P=0.0013; OR, 2.14). Furthermore, the rare gain-of-function SERT I425V variant was observed in 3 male siblings with TD and/or OCD and in their father. Thus, the cumulative count of SERT I425V becomes 1.57% in OCD/TD spectrum conditions versus 0.15% in controls, with a recalculated, family-adjusted significance of (2) = 15.03 (P<0.0001; OR, 9.0; total worldwide genotyped, 2914). This report provides a unique combination of common and rare variants in one gene in TD, all of which are associated with SERT gain of function. Thus, altered SERT activity represents a potential contributor to serotonergic abnormalities in TD. The present results call for replication in a similarly intensively evaluated sample. (c) 2013 Movement Disorder Society
C1 [Moya, Pablo R.; Wendland, Jens R.; Rubenstein, Liza M.; Murphy, Dennis L.] NIMH, Clin Sci Lab, Intramural Res Program, Bethesda, MD 20892 USA.
[Timpano, Kiara R.] Univ Miami, Dept Psychol, Coral Gables, FL 33124 USA.
[Heiman, Gary A.; Tischfield, Jay A.] Rutgers State Univ, Human Genet Inst New Jersey, Piscataway, NJ USA.
[Heiman, Gary A.; Tischfield, Jay A.] Rutgers State Univ, Dept Genet, Piscataway, NJ USA.
[King, Robert A.] Yale Univ, Ctr Child Study, New Haven, CT 06520 USA.
[Andrews, Anne M.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA.
[Andrews, Anne M.] Univ Calif Los Angeles, Calif Nano Syst Inst, Los Angeles, CA USA.
[Ramamoorthy, Samanda] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA USA.
[McMahon, Francis J.] NIMH, Human Genet Branch, Intramural Res Program, Bethesda, MD 20892 USA.
[Moya, Pablo R.] Univ Valparaiso, Fac Sci, Dept Physiol, Valparaiso, Chile.
RP Moya, PR (reprint author), NIMH, Clin Sci Lab, Intramural Res Program, 10-3D41,10 Ctr Dr, Bethesda, MD 20892 USA.
EM moyap@mail.nih.gov
RI Andrews, Anne/B-4442-2011;
OI Andrews, Anne/0000-0002-1961-4833; McMahon, Francis/0000-0002-9469-305X;
Tischfield, Jay/0000-0003-3217-8287; Timpano, Kiara/0000-0002-0665-8722
FU National Institute of Mental Health (NIMH) Intramural Research Program;
National Alliance for Research on Schizophrenia and Depression; New
Jersey Center for Tourette Syndrome and Associated Disorders; NIMH
[R01-MH092293, R01-MH064756]
FX Contract grant sponsor: National Institute of Mental Health (NIMH)
Intramural Research Program.; Contract grant sponsor: National Alliance
for Research on Schizophrenia and Depression.; Contract grant sponsor:
New Jersey Center for Tourette Syndrome and Associated Disorders.;
Contract grant sponsor: NIMH, grants R01-MH092293 and R01-MH064756.
NR 69
TC 9
Z9 10
U1 5
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0885-3185
J9 MOVEMENT DISORD
JI Mov. Disord.
PD AUG
PY 2013
VL 28
IS 9
BP 1263
EP 1270
DI 10.1002/mds.25460
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 210KA
UT WOS:000323830100020
PM 23630162
ER
PT J
AU Appenzeller, S
Schulte, C
Thier, S
Hopfner, F
Pendziwiat, M
Papengut, F
Klein, C
Hagenah, J
Kasten, M
Srulijes, K
Berg, D
Gasser, T
Singleton, A
Deuschl, G
Kuhlenbaumer, G
AF Appenzeller, Silke
Schulte, Claudia
Thier, Sandra
Hopfner, Franziska
Pendziwiat, Manuela
Papengut, Frank
Klein, Christine
Hagenah, Johann
Kasten, Meike
Srulijes, Karin
Berg, Daniela
Gasser, Thomas
Singleton, Andrew
Deuschl, Guenther
Kuhlenbaeumer, Gregor
TI No association between polymorphisms in the glutamate transporter SLC1A2
and Parkinson's disease
SO MOVEMENT DISORDERS
LA English
DT Letter
ID ESSENTIAL TREMOR; LINGO1
C1 [Appenzeller, Silke; Pendziwiat, Manuela; Kuhlenbaeumer, Gregor] Univ Kiel, Inst Expt Med, D-24105 Kiel, Germany.
[Schulte, Claudia; Srulijes, Karin; Berg, Daniela; Gasser, Thomas] Hertie Inst Clin Brain Res, Tubingen, Germany.
[Thier, Sandra; Hopfner, Franziska; Papengut, Frank; Deuschl, Guenther] Univ Hosp Schleswig Holstein, Dept Neurol, Kiel, Germany.
[Klein, Christine; Hagenah, Johann; Kasten, Meike] Med Univ Lubeck, Dept Neurol, Sect Clin & Mol Neurogenet, Lubeck, Germany.
[Kasten, Meike] Univ Hosp Schleswig Holstein, Dept Psychiat & Psychotherapy, Lubeck, Germany.
[Srulijes, Karin; Berg, Daniela; Gasser, Thomas] Univ Tubingen, Dept Neurodegenerat, Tubingen, Germany.
[Singleton, Andrew] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
RP Kuhlenbaumer, G (reprint author), Univ Kiel, Inst Expt Med, Dept Mol Neurobiol, Arnold Heller Str 3, D-24105 Kiel, Germany.
EM g.kuhlenbaeumer@neurologie.uni-kiel.de
RI Singleton, Andrew/C-3010-2009; Deuschl, Gunther/A-7986-2010;
OI Schulte, Claudia/0000-0003-4006-1265
FU Intramural NIH HHS [Z01 AG000949-03]; NIA NIH HHS [Z01 AG000949, ZO1
AG000949-06]
NR 7
TC 2
Z9 2
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0885-3185
J9 MOVEMENT DISORD
JI Mov. Disord.
PD AUG
PY 2013
VL 28
IS 9
BP 1305
EP 1306
DI 10.1002/mds.25330
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA 210KA
UT WOS:000323830100029
PM 23390085
ER
PT J
AU Mendez-Catala, CF
Gretton, S
Vostrov, A
Pugacheva, E
Farrar, D
Ito, Y
Docquier, F
Kita, GX
Murrell, A
Lobanenkov, V
Klenova, E
AF Mendez-Catala, Claudia Fabiola
Gretton, Svetlana
Vostrov, Alexander
Pugacheva, Elena
Farrar, Dawn
Ito, Yoko
Docquier, France
Kita, Georgia-Xanthi
Murrell, Adele
Lobanenkov, Victor
Klenova, Elena
TI A Novel Mechanism for CTCF in the Epigenetic Regulation of Bax in Breast
Cancer Cells
SO NEOPLASIA
LA English
DT Article
ID TUMOR-SUPPRESSOR GENE; BCL-2 FAMILY; PROTEIN EXPRESSION;
BINDING-PROTEIN; HUMAN GENOME; APOPTOSIS; DEATH; TRANSCRIPTION; P53;
DIFFERENTIATION
AB We previously reported the association of elevated levels of the multifunctional transcription factor, CCCTC binding factor (CTCF), in breast cancer cells with the specific anti-apoptotic function of CTCF. To understand the molecular mechanisms of this phenomenon, we investigated regulation of the human Bax gene by CTCF in breast and non-breast cells. Two CTCF binding sites (CTSs) within the Bax promoter were identified. In all cells, breast and non-breast, active histone modifications were present at these CTSs, DNA harboring this region was unmethylated, and levels of Bax mRNA and protein were similar. Nevertheless, up-regulation of Bax mRNA and protein and apoptotic cell death were observed only in breast cancer cells depleted of CTCF. We proposed that increased CTCF binding to the Bax promoter in breast cancer cells, by comparison with non-breast cells, may be mechanistically linked to the specific apoptotic phenotype in CTCF-depleted breast cancer cells. In this study, we show that CTCF binding was enriched at the Bax CTSs in breast cancer cells and tumors; in contrast, binding of other transcription factors (SP1, WT1, EGR1, and c-Myc) was generally increased in non-breast cells and normal breast tissues. Our findings suggest a novel mechanism for CTCF in the epigenetic regulation of Bax in breast cancer cells, whereby elevated levels of CTCF support preferential binding of CTCF to the Bax CTSs. In this context, CTCF functions as a transcriptional repressor counteracting influences of positive regulatory factors; depletion of breast cancer cells from CTCF therefore results in the activation of Bax and apoptosis.
C1 [Mendez-Catala, Claudia Fabiola; Gretton, Svetlana; Farrar, Dawn; Kita, Georgia-Xanthi; Klenova, Elena] Univ Essex, Sch Biol Sci, Colchester CO4 3SQ, Essex, England.
[Vostrov, Alexander; Pugacheva, Elena; Lobanenkov, Victor] NIAID, Mol Pathol Sect, Immunopathol Lab, NIH, Rockville, MD USA.
[Ito, Yoko; Murrell, Adele] Canc Res UK Cambridge Res Inst, Cambridge, England.
[Docquier, France] Anglia Ruskin Univ, Helen Rollason Res Lab, PMI 208, PMI, Chelmsford, Essex, England.
RP Klenova, E (reprint author), Univ Essex, Sch Biol Sci, Wivenhoe Pk, Colchester CO4 3SQ, Essex, England.
EM klenovae@essex.ac.uk
FU CONACyT, Mexico; Breast Cancer Campaign; Breast Cancer Research Trust;
Helen Rollason Cancer Charity; Medical Research Council; Cancer Research
UK; Research Promotion Fund from the University of Essex; Intramural
Research Program of the National Institutes of Health, National
Institute of Allergy and Infectious Diseases; Cancer Research UK Senior
Cancer Research Fellowship; Association for International Cancer
Research; University of Cambridge; Hutchison Whampoa Limited
FX This work was supported by the Postgraduate Scholarship from CONACyT,
Mexico (C.F.M.-C.), Breast Cancer Campaign (F.D. and E.K.), Breast
Cancer Research Trust (G.-X.K. and E.K.), Helen Rollason Cancer Charity
(F.D.), Medical Research Council and Cancer Research UK (D.F. and E.K.),
Research Promotion Fund from the University of Essex (F.D., D.F., and
E.K.), the Intramural Research Program of the National Institutes of
Health, National Institute of Allergy and Infectious Diseases (A.V.,
E.P., and V.L.), Cancer Research UK Senior Cancer Research Fellowship
(A.M.), and Association for International Cancer Research (A.M. and
Y.I.), as well as the support of the University of Cambridge, Cancer
Research UK, and Hutchison Whampoa Limited (A.M. and Y.I.).
NR 53
TC 7
Z9 9
U1 0
U2 2
PU NEOPLASIA PRESS
PI ANN ARBOR
PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648
USA
SN 1522-8002
J9 NEOPLASIA
JI Neoplasia
PD AUG
PY 2013
VL 15
IS 8
BP 898
EP +
DI 10.1593/neo.121948
PG 25
WC Oncology
SC Oncology
GA 219EM
UT WOS:000324488800004
PM 23908591
ER
PT J
AU Madka, V
Zhang, YT
Li, Q
Mohammed, A
Sindhwani, P
Lightfoot, S
Wu, XR
Kopelovich, L
Rao, CV
AF Madka, Venkateshwar
Zhang, Yuting
Li, Qian
Mohammed, Altaf
Sindhwani, Puneet
Lightfoot, Stan
Wu, Xue-Re
Kopelovich, Levy
Rao, Chinthalapally V.
TI p53-stabilizing Agent CP-31398 Prevents Growth and Invasion of
Urothelial Cancer of the Bladder in Transgenic UPII-SV40T Mice
SO NEOPLASIA
LA English
DT Article
ID TRANSITIONAL-CELL CARCINOMA; MALE ICR MICE; URINARY-BLADDER; WILD-TYPE;
MUTANT P53; TUMOR PROGRESSION; MOUSE MODEL; CARCINOGENESIS; EXPRESSION;
SUPPRESSION
AB The high prevalence of bladder cancer and its recurrence make it an important target for chemoprevention. About half of invasive urothelial tumors have mutations in p53. We determined the chemopreventive efficacy of a p53-stabilizing agent, CP-31398, in a transgenic UPII-SV40T mouse model of bladder transitional cell carcinoma (TCC) that strongly resembles human TCC. After genotyping, six-week-old UPII-SV40T mice (n = 30/group) were fed control (AIN-76A) or experimental diets containing 150 or 300 ppm of CP-31398 for 34 weeks. Progression of bladder cancer growth was monitored by magnetic resonance imaging. At 40 weeks of age, all mice were killed; urinary bladders were collected to determine weights, tumor incidence, and histopathology. There was a significant increase in bladder weights of transgenic versus wild-type mice (male: 140.2 mg vs 27.3 mg, P < .0001; female: 34.2 mg vs 14.8 mg, P < .0001). A significant decrease in the bladder tumor weights (by 68.6-80.2%, P < .0001 in males and by 36.9-55.3%, P < .0001 in females) was observed in CP-31398-treated mice. Invasive papillary TCC incidence was 100% in transgenic mice fed control diet. Both male and female mice exposed to CP-31398 showed inhibition of invasive TCC. CP-31398 (300 ppm) completely blocked invasion in female mice. Molecular analysis of the bladder tumors showed an increase in apoptosis markers (p53, p21, Bax, and Annexin V) with a decrease in vascular endothelial growth factor in transgenic mice fed CP-31398. These results suggest that p53-modulating agents can serve as potential chemopreventive agents for bladder TCC.
C1 [Madka, Venkateshwar; Zhang, Yuting; Li, Qian; Mohammed, Altaf; Rao, Chinthalapally V.] Univ Oklahoma, Hlth Sci Ctr, Ctr Canc Prevent & Drug Dev, Dept Med,Hem Onc Sect,PC Stephenson Canc Ctr, Oklahoma City, OK 73104 USA.
[Sindhwani, Puneet] Univ Oklahoma, Hlth Sci Ctr, Dept Urol, Oklahoma City, OK 73104 USA.
[Lightfoot, Stan] Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK 73104 USA.
[Wu, Xue-Re] NYU Med Ctr, Dept Urol, New York, NY 10016 USA.
[Kopelovich, Levy] NCI, Canc Prevent Div, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA.
RP Rao, CV (reprint author), Univ Oklahoma, Hlth Sci Ctr, Ctr Canc Prevent & Drug Dev, 975 NE 10th St,BRC Bldg 2,Room 1203, Oklahoma City, OK 73104 USA.
EM cv-rao@ouhsc.edu
FU National Institute of Health/National Cancer Institute (NIH/NCI)
[NCI-CN53300]
FX We thank the National Institute of Health/National Cancer Institute
(NIH/NCI) for funding (NCI-CN53300) and the University of Oklahoma
Health Sciences Center Rodent Barrier Facility and Dr Rheal Towner from
the Small Rodent Imaging Facility, Oklahoma Medical Research Foundation.
NR 48
TC 12
Z9 12
U1 0
U2 1
PU NEOPLASIA PRESS
PI ANN ARBOR
PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648
USA
SN 1522-8002
J9 NEOPLASIA
JI Neoplasia
PD AUG
PY 2013
VL 15
IS 8
BP 966
EP +
DI 10.1593/neo.13704
PG 10
WC Oncology
SC Oncology
GA 219EM
UT WOS:000324488800009
PM 23908596
ER
PT J
AU Linehan, WM
Srinivasan, R
Garcia, JA
AF Linehan, W. Marston
Srinivasan, Ramaprasad
Garcia, Jorge A.
TI Non-Clear Cell Renal Cancer: Disease-Based Management and Opportunities
for Targeted Therapeutic Approaches
SO SEMINARS IN ONCOLOGY
LA English
DT Review
ID COLLECTING DUCT CARCINOMA; HOGG-DUBE-SYNDROME; TUBEROUS SCLEROSIS
COMPLEX; FUMARATE-HYDRATASE GENE; MULTICENTER PHASE-II; HEREDITARY
LEIOMYOMATOSIS; MEDULLARY CARCINOMA; SUCCINATE-DEHYDROGENASE; KIDNEY
CANCER; GERMLINE MUTATIONS
AB A better understanding of the biology of renal cell carcinoma (RCC) has significantly changed the treatment paradigm of the disease. Several novel vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) inhibitors have been approved recently by the US Food and Drug Administration. Unfortunately, the vast majority of clinical trials conducted today have been aimed to include patients with clear cell RCC, which remains the most common histologic subtype of the disease. Non-clear cell RCC represents approximately 20%-25% of all RCC patients. Non-clear cell RCC is made up of multiple histologic subtypes, each with a different molecular printing profile. Although VEGF and TORC inhibitors are commonly used in the management of this cohort of patients, non-clear cell histologies do not appear to be related to the von Hippel-Lindau gene (VHL). As such, the clinical efficacy of the existing agents is quite limited. There is a need to develop more rational therapeutic approaches that specifically target the biology of each of the different subtypes of non-clear cell RCC. In this review, we discuss molecular and clinical characteristics of each of the non-clear cell RCC subtypes and describe ongoing efforts to develop novel agents for this subset of patients. Published by Elsevier Inc.
C1 [Linehan, W. Marston; Srinivasan, Ramaprasad] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Garcia, Jorge A.] Cleveland Clin, Solid Tumor Oncol Dept, Taussig Canc Inst, Cleveland, OH 44106 USA.
RP Linehan, WM (reprint author), NCI, Urol Oncol Branch, 10 Ctr Dr,MSC 1107,CRC Room 1W-5940, Bethesda, MD 20892 USA.
EM WML@nih.gov
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research. The authors
thank Georgia Platen Shaw for the outstanding editorial and graphics
support.
NR 91
TC 15
Z9 15
U1 0
U2 7
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0093-7754
J9 SEMIN ONCOL
JI Semin. Oncol.
PD AUG
PY 2013
VL 40
IS 4
BP 511
EP 520
DI 10.1053/j.seminonco1.2013.05.009
PG 10
WC Oncology
SC Oncology
GA 214QF
UT WOS:000324149700013
PM 23972715
ER
PT J
AU Zhen, ZP
Tang, W
Guo, CL
Chen, HM
Lin, X
Liu, G
Fei, BW
Chen, XY
Xu, BQ
Xie, J
AF Zhen, Zipeng
Tang, Wei
Guo, Cunlan
Chen, Hongmin
Lin, Xin
Liu, Gang
Fei, Baowei
Chen, Xiaoyuan
Xu, Binqian
Xie, Jin
TI Ferritin Nanocages To Encapsulate and Deliver Photosensitizers for
Efficient Photodynamic Therapy against Cancer
SO ACS NANO
LA English
DT Article
DE photodynamic therapy; photosensitizer; targeted delivery; ferritin;
nanoparticle
ID ZINC PHTHALOCYANINE; PROSTATE-CANCER; COMBINATION THERAPY;
DRUG-DELIVERY; NANOPARTICLES; APOFERRITIN; TUMORS; GROWTH; MODEL
AB Photodynamic therapy is an emerging treatment modality that is under, intensive preclinical and clinical investigations for many types of disease including cancer. Despite the promise, there is a lack of a reliable drug delivery vehicle that can transport photosensitizers (PSs) to tumors in a site-specific manner: Previous efforts have been focused on polymer- or liposome-based nanocarriers, which are usually associated with a suboptimal PS loading rate and a large particle size. We report herein that a RGD4C-modified ferritin (RFRT), a protein-based nanoparticle, can serve as a safe and efficient PS vehicle. Zinc hexadecafluorophthalocyanine (ZnF16Pc), a potent PS with a high 102 quantum yield but poor water solubility, can be encapsulated into RFRTs with a loading rate as high as similar to 60 wt % (i.e, 13 mg of ZnF16Pc can be loaded on 1 mg of RAM), which far exceeds those reported previously.. Despite the high loading, the ZnF16Pc-loaded Fans (P-RFRTs) show an overall particle size of 18.6 +/- 2.6 nm, which is significantly smaller than other PS-nanocarrier conjugates: When tested on U87MG subcutaneous tumor models, P-RFRTs showed a high tumor accumulation rate (tumor-to-normal tissue ratio of 26.82 +/- 4.07at 24 h), a good tumor inhibition rate (8164% on day 12), as well as minimal toxicity to the skin and other major organs. This technology can be extended to deliver other metal-containing PSs and holds great clinical translation potential.
C1 [Zhen, Zipeng; Tang, Wei; Chen, Hongmin; Xie, Jin] Univ Georgia, Dept Chem, Athens, GA 30602 USA.
[Zhen, Zipeng; Tang, Wei; Chen, Hongmin; Xie, Jin] Univ Georgia, Bioimaging Res Ctr BIRC, Athens, GA 30602 USA.
[Guo, Cunlan; Xu, Binqian] Univ Georgia, Dept Phys, Athens, GA 30602 USA.
[Lin, Xin; Chen, Xiaoyuan] NIBIB, NIH, Rockville, MD 20852 USA.
[Liu, Gang] Xiamen Univ, Ctr Mol Imaging & Translat Med, Sch Publ Hlth, Xiamen 361102, Peoples R China.
[Liu, Gang] Xiamen Univ, State Key Lab Cellular Stress Biol, Xiamen 361102, Peoples R China.
[Liu, Gang] Xiamen Univ, Sch Life Sci, Xiamen 361102, Peoples R China.
[Fei, Baowei] Emory Univ, Dept Biomed Engn, Atlanta, GA 30329 USA.
[Fei, Baowei] Georgia Inst Technol, Atlanta, GA 30329 USA.
RP Xie, J (reprint author), Univ Georgia, Dept Chem, Athens, GA 30602 USA.
EM jinxie@uga.edu
RI Guo, Cunlan/E-8077-2011; Fei, Baowei /E-6898-2014; Chen,
Hongmin/B-9555-2011; Fei, Baowei/A-6504-2011
OI Fei, Baowei /0000-0002-9123-9484; Fei, Baowei/0000-0002-9123-9484
FU NCl/NIH [5R00CA153772, R01CA156775]; UGA; U.S. National Science
Foundation [ECCS0823849, CBET 1139057]; Georgia Cancer Coalition
Distinguished Clinicians and Scientists Award; Intramural Research
Program of NIBIB; NIH; Major State Basic Research Development Program of
China (973 Program) [2013CB733802]; National Nature Science of
Foundation of China (NSFC) [81101101, 51273165]; Key Project of Chinese
Ministry of Education [212149]
FX This work was supported by an NCl/NIH R00 grant (5R00CA153772, JX.), a
UGA startup grant (IX.), U.S. National Science Foundation grants
(ECCS0823849 and CBET 1139057, B.X.), NCl/NIH R01 grant (R01CA156775,
B.F.), Georgia Cancer Coalition Distinguished Clinicians and Scientists
Award (B.F.), and the Intramural Research Program of NIBIB, NIH. We
thank the support from the Major State Basic Research Development
Program of China (973 Program, 2013CB733802), the National Nature
Science of Foundation of China (NSFC, 81101101, 51273165), and the Key
Project of Chinese Ministry of Education (212149). We are grateful to
Prof. J. Frangioni and Prof. H. Soo at Harvard Medical School for
generously providing the ZW800 dye.
NR 40
TC 73
Z9 76
U1 30
U2 167
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1936-0851
J9 ACS NANO
JI ACS Nano
PD AUG
PY 2013
VL 7
IS 8
BP 6988
EP 6996
DI 10.1021/nn402199g
PG 9
WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience &
Nanotechnology; Materials Science, Multidisciplinary
SC Chemistry; Science & Technology - Other Topics; Materials Science
GA 210DX
UT WOS:000323810600060
PM 23829542
ER
PT J
AU Hoffman, AF
Lupica, CR
AF Hoffman, Alexander F.
Lupica, Carl R.
TI Synaptic Targets of Delta(9)-Tetrahydrocannabinol in the Central Nervous
System
SO COLD SPRING HARBOR PERSPECTIVES IN MEDICINE
LA English
DT Article
ID LONG-TERM POTENTIATION; VENTRAL TEGMENTAL AREA; CB1 CANNABINOID
RECEPTOR; MIDBRAIN DOPAMINE NEURONS; NUCLEUS-ACCUMBENS; CHRONIC
DELTA-9-TETRAHYDROCANNABINOL; HIPPOCAMPAL-NEURONS; RAT-BRAIN;
ENDOCANNABINOID RELEASE; GLUTAMATERGIC SYNAPSES
AB The availability of potent synthetic agonists for cannabinoid receptors has facilitated our understanding of cannabinoid actions on synaptic transmission in the central nervous system. Moreover, the ability of these compounds to inhibit neurotransmitter release at many central synapses is thought to underlie most of the behavioral effects of cannabinoid agonists. However, despite the widespread use and misuse of marijuana, and recognition of its potential adverse psychological effects in humans, comparatively few studies have examined the actions of its primary psychoactive constituent, Delta(9)-tetrahydrocannabinol (THC), at well-defined synaptic pathways. Here we examine the recent literature describing the effects of acute and repeated THC exposure on synaptic function in several brain regions and explore the importance of these neurobiological actions of THC in drug addiction.
C1 [Hoffman, Alexander F.; Lupica, Carl R.] Natl Inst Drug Abuse, NIH, US Dept Hlth & Human Serv, Intramural Res Program,Electrophysiol Res Sect, Baltimore, MD 21224 USA.
RP Lupica, CR (reprint author), Natl Inst Drug Abuse, NIH, US Dept Hlth & Human Serv, Intramural Res Program,Electrophysiol Res Sect, Baltimore, MD 21224 USA.
EM clupica@intra.nida.nih.gov
RI Hoffman, Alexander/H-3035-2012
OI Hoffman, Alexander/0000-0002-2676-0628
FU U.S. Department of Health and Human Services; National Institutes of
Health; National Institute on Drug Abuse Intramural Research Program;
National Institute on Drug Abuse [DA14263]
FX This work is supported by the U.S. Department of Health and Human
Services, The National Institutes of Health, and the National Institute
on Drug Abuse Intramural Research Program, and earlier studies were
supported by a grant from the National Institute on Drug Abuse (DA14263
to C.R.L.).
NR 109
TC 4
Z9 4
U1 1
U2 23
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 2157-1422
J9 CSH PERSPECT MED
JI Cold Spring Harb. Perspect. Med.
PD AUG
PY 2013
VL 3
IS 8
AR a012203
DI 10.1101/cshperspect.a012237
PG 14
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 211WB
UT WOS:000323941200007
ER
PT J
AU Shirota, H
Klinman, DM
AF Shirota, Hidekazu
Klinman, Dennis M.
TI Use of CpG oligonucleotides for cancer immunotherapy and their effect on
immunity in the tumor microenvironment
SO IMMUNOTHERAPY
LA English
DT Editorial Material
DE cancer immunotherapy; CpG oligonucleotide; myeloid-derived suppressor
cell; Toll-like receptor 9
ID SUPPRESSOR-CELLS; ESTABLISHED TUMORS; BACTERIAL-DNA; T-CELLS;
PF-3512676; REGRESSION; INJECTION; CARCINOMA; MELANOMA
C1 [Shirota, Hidekazu] Tohoku Univ Hosp, Dept Clin Oncol, Sendai, Miyagi 9808574, Japan.
[Klinman, Dennis M.] Natl Canc Inst, Frederick, MD 21702 USA.
RP Shirota, H (reprint author), Tohoku Univ Hosp, Dept Clin Oncol, 1-1 Seiryo machi,Aoba ku, Sendai, Miyagi 9808574, Japan.
EM shirotah@idac.tohoku.ac.jp
NR 17
TC 5
Z9 5
U1 0
U2 9
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1750-743X
J9 IMMUNOTHERAPY-UK
JI Immunotherapy
PD AUG
PY 2013
VL 5
IS 8
BP 787
EP 789
DI 10.2217/IMT.13.70
PG 3
WC Immunology
SC Immunology
GA 202PL
UT WOS:000323230400002
PM 23902544
ER
PT J
AU Otto, M
AF Otto, Michael
TI Community-associated MRSA: What makes them special?
SO INTERNATIONAL JOURNAL OF MEDICAL MICROBIOLOGY
LA English
DT Review
DE Staphylococcus aureus; MRSA; Community-associated MRSA; Alpha-toxin;
Panton-Valentine leukocidin; Phenol-soluble modulin
ID RESISTANT STAPHYLOCOCCUS-AUREUS; PANTON-VALENTINE LEUKOCIDIN; CATABOLIC
MOBILE ELEMENT; ALPHA-HEMOLYSIN; VIRULENCE DETERMINANTS; HUMAN
NEUTROPHILS; SKIN INFECTION; NASAL CARRIAGE; USA300; TOXIN
AB While infections with methicillin-resistant Staphylococcus aureus (MRSA) were traditionally restricted to the hospital setting, novel MRSA strains emerged over the last two decades that have the capacity to infect otherwise healthy people outside of the hospital setting. These community-associated (CA-)MRSA strains combine methicillin resistance with enhanced virulence and fitness. Interestingly, CA-MRSA strains emerged globally and from different backgrounds, indicating that the "trade-off" between maintaining sufficient levels of methicillin resistance and obtaining enhanced virulence at a low fitness cost was achieved on several occasions in convergent evolution. However, frequently this process comprised similar changes. First and foremost, all CA-MRSA strains typically carry a novel type of methicillin resistance locus that appears to cause less of a fitness burden. Additionally, acquisition of specific toxin genes, most notably that encoding Panton-Valentine leukocidin (PVL), and adaptation of gene expression of genome-encoded toxins, such as alpha-toxin and phenol-soluble modulins (PSMs), further contributed to the evolution of CA-MRSA. Finally, the exceptional epidemiological success of the USA300 CA-MRSA clone in particular may have been due to yet another gene acquisition, namely that of the speG gene, which is located on the arginine catabolic mobile element (ACME) and involved in detoxifying harmful host-derived polyamines. Published by Elsevier GmbH.
C1 [Otto, Michael] NIAID, Pathogen Mol Genet Sect, Lab Human Bacterial Pathogenesis, NIH, Bethesda, MD 20892 USA.
RP Otto, M (reprint author), 9000 Rockville Pike,Bldg 33 1W10, Bethesda, MD 20892 USA.
EM motto@niaid.nih.gov
OI Otto, Michael/0000-0002-2222-4115
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, NIH
FX This work was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, NIH.
NR 76
TC 51
Z9 52
U1 3
U2 52
PU ELSEVIER GMBH, URBAN & FISCHER VERLAG
PI JENA
PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY
SN 1438-4221
J9 INT J MED MICROBIOL
JI Int. J. Med. Microbiol.
PD AUG
PY 2013
VL 303
IS 6-7
BP 324
EP 330
DI 10.1016/j.ijmm.2013.02.007
PG 7
WC Microbiology; Virology
SC Microbiology; Virology
GA 210BG
UT WOS:000323803700007
PM 23517691
ER
PT J
AU Cuthbert, BN
Kozak, MJ
AF Cuthbert, Bruce N.
Kozak, Michael J.
TI Constructing Constructs for Psychopathology: The NIMH Research Domain
Criteria
SO JOURNAL OF ABNORMAL PSYCHOLOGY
LA English
DT Editorial Material
DE Research Domain Criteria; RDoC; psychiatric diagnosis; psychiatric
nosology
ID COGNITIVE NEUROSCIENCE; SOCIAL ANHEDONIA; MENTAL-DISORDERS; VERBAL
REPORTS; SPECTRUM; MODEL; CLASSIFICATION; SCHIZOPHRENIA; PSYCHOLOGY;
OPPORTUNITIES
AB As a commentary for the special section on Reconceptualizing the Classification of Mental Disorders, this article begins with a description of the impetus for the U.S. National Institute of Mental Health's (NIMH) Research Domain Criteria (RDoC) initiative and provides an update of progress on that initiative to date. The commentary then engages the articles in this special section, beginning with a response to Berenbaum's concern that the RDoC approach to sorting constructs across multiple units of analysis espouses a de facto biological fundamentalism. This leads us to delineate the relationship between RDoC and the NIMH priorities relevant to this initiative. The commentary then considers how Patrick's iterative "construct-network" method can be applied to RDoC construct validation, highlighting several aspects that are particularly useful. One aspect of this work involves determining subject inclusion and exclusion criteria that provide an appropriate range of variance. Finally, this commentary considers the Bilder group's article, explicating the ways in which multilevel models can foster development of hypotheses and informatics approaches needed for further RDoC progress.
C1 [Cuthbert, Bruce N.; Kozak, Michael J.] NIMH, Bethesda, MD 20892 USA.
RP Cuthbert, BN (reprint author), NIMH, NIH, Bethesda, MD 20892 USA.
EM bcuthber@mail.nih.gov
NR 48
TC 88
Z9 90
U1 4
U2 36
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0021-843X
J9 J ABNORM PSYCHOL
JI J. Abnorm. Psychol.
PD AUG
PY 2013
VL 122
IS 3
BP 928
EP 937
DI 10.1037/a0034028
PG 10
WC Psychology, Clinical; Psychology, Multidisciplinary
SC Psychology
GA 210CO
UT WOS:000323807100030
PM 24016027
ER
PT J
AU Clifford, DB
Nath, A
Cinque, P
Brew, BJ
Zivadinov, R
Gorelik, L
Zhao, ZM
Duda, P
AF Clifford, David B.
Nath, Avindra
Cinque, Paola
Brew, Bruce J.
Zivadinov, Robert
Gorelik, Leonid
Zhao, Zhenming
Duda, Petra
TI A study of mefloquine treatment for progressive multifocal
leukoencephalopathy: results and exploration of predictors of PML
outcomes
SO JOURNAL OF NEUROVIROLOGY
LA English
DT Article
DE Mefloquine; Leukoencephalopathy; Progressive multifocal; JC virus;
Magnetic resonance imaging
ID CEREBROSPINAL-FLUID; DISEASE; PATHOGENESIS; BRAIN
AB Immune reconstitution has improved outcomes for progressive multifocal leukoencephalopathy (PML), a potentially lethal brain disease caused by JC virus (JCV). However, an antiviral treatment to control JCV is needed when immune reconstitution is delayed or not possible. On the basis of in vitro efficacy, this study evaluated the effect of mefloquine on PML and factors that may predict PML outcomes. This 38-week, open-label, randomized, parallel-group, proof-of-concept study compared patients with PML who received standard of care (SOC) with those who received SOC plus mefloquine (250 mg for 3 days, then 250 mg weekly). Patients randomized to SOC could add mefloquine treatment at week 4. The primary endpoint was change from baseline to weeks 4 and 8 in JCV DNA copy number (load) in cerebrospinal fluid (CSF). Exploratory analyses evaluated factors that might correlate with clinical outcome. The majority of enrolled patients were HIV positive. Preplanned interim data analyses suggested that the study was unlikely to successfully demonstrate a significant difference between groups; therefore, the study was terminated prematurely. There was no significant difference between groups in CSF JCV DNA loads or clinical/MRI findings. Decrease in CSF JCV DNA load from baseline to week 4 was associated with a better clinical outcome at 16 weeks, as measured by Karnofsky scores. This study found no evidence of anti-JCV activity by mefloquine. An early decrease of CSF JCV DNA load appears to be associated with a better clinical outcome.
C1 [Clifford, David B.] Washington Univ, Dept Neurol, St Louis, MO 63110 USA.
[Nath, Avindra] NINDS, Sect Infect Nervous Syst, NIH, Bethesda, MD 20892 USA.
[Cinque, Paola] Ist Sci San Raffaele, Dept Infect Dis, I-20127 Milan, Italy.
[Brew, Bruce J.] St Vincents Hosp, Dept Neurol, Sydney, NSW 2010, Australia.
[Brew, Bruce J.] St Vincents Hosp, Dept HIV Med, Sydney, NSW 2010, Australia.
[Brew, Bruce J.] Univ New S Wales, Sydney, NSW, Australia.
[Zivadinov, Robert] Buffalo Neuroimaging Anal Ctr, Dept Neurol, Buffalo, NY USA.
[Gorelik, Leonid] Biogen Idec Inc, Dept Res, Weston, MA USA.
[Zhao, Zhenming] Pharmaceut Prod Dev LLC, Austin, TX 78744 USA.
[Duda, Petra] Biogen Idec Inc, Dept Med Res, Weston, MA USA.
[Brew, Bruce J.] St Vincents Hosp, Dept Neurol, Sydney, NSW 20120, Australia.
[Zivadinov, Robert] Jacobs Neurol Inst, Buffalo, NY 14203 USA.
[Gorelik, Leonid; Duda, Petra] Biogen Idec Inc, Cambridge, MA 02142 USA.
RP Clifford, DB (reprint author), Washington Univ, Dept Neurol, Box 8111,660 South Euclid Ave, St Louis, MO 63110 USA.
EM cliffordd@neuro.wustl.edu
RI Brew, Bruce/J-6513-2012
FU Biogen Idec Inc.; Elan Pharmaceuticals, Inc.
FX This study was supported by Biogen Idec Inc. and Elan Pharmaceuticals,
Inc. Funding for assistance with medical writing, as well as editorial
support, was also provided by Biogen Idec Inc. and Elan Pharmaceuticals,
Inc. Exploratory analyses were performed by BioStat Solutions Inc., in
collaboration with Nigel Dodd of Biogen Idec Inc. The first author, Dr.
Clifford, prepared the initial draft; assistance in medical writing was
provided by Katherine Hauswirth and editorial support was provided by
Jackie Cannon, both of Infusion Communications. The authors would like
to acknowledge the following principal investigators/sites that enrolled
patients for this study: Keikawus Arasteh, MD,
Auguste-Viktoria-Krankenhaus Klinikum, Berlin, Germany; Gabriele Arendt,
MD, Heinrich-Heine Universitat, Neurologische Klinik, Dusseldorf,
Germany; David B. Clifford, MD, Washington University in St. Louis, St.
Louis, MO, USA; Bruce A. Cohen, MD, Northwestern University, Evanston,
IL, USA; Igor Koralnik, MD, Beth Israel Deaconess Medical Center,
Boston, MA, USA; Adriano Lazzarin, MD, Divisione di Malattie Infettive,
Fondazione Centro San Raffaele del Monte Tabor, Milan, Italy; Justin
McArthur, MBBS, MPH, Johns Hopkins University, Baltimore, MD, USA; Jose
Miro, MD, Hospital Clinic I Provincial de Barcelona, Barcelona, Spain;
Augusto Cesar Penalva de Oliveira, Ph.D., Instituto de Infectologia
Emillo Ribas, Sao Paulo, Brazil; Thorsten Rosenkranz, MD, Asklepios
Klinik St. George, Hamburg, Germany; and David M. Simpson, MD, Mount
Sinai Medical Center, New York, NY, USA. The authors would also like to
acknowledge the investigators at the Buffalo Neuroimaging Analysis
Center, Buffalo, NY, USA, who collected the scans and performed the
analyses: Cheryl Kennedy, LMSW, MPH; Niels Bergsland, M.Sc.; Michael G.
Dwyer, M.Sc.; Jackie Durfee, BS; Sara Hussein, BS; and Deepa P.
Ramasamy, MD.
NR 12
TC 40
Z9 40
U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1355-0284
J9 J NEUROVIROL
JI J. Neurovirol.
PD AUG
PY 2013
VL 19
IS 4
BP 351
EP 358
DI 10.1007/s13365-013-0173-y
PG 8
WC Neurosciences; Virology
SC Neurosciences & Neurology; Virology
GA 209FX
UT WOS:000323741400005
PM 23733308
ER
PT J
AU Cao, Y
Chen, AM
Bottai, M
Caldwell, KL
Rogan, WJ
AF Cao, Yang
Chen, Aimin
Bottai, Matteo
Caldwell, Kathleen L.
Rogan, Walter J.
TI The Impact of Succimer Chelation on Blood Cadmium in Children with
Background Exposures: A Randomized Trial
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID DIMERCAPTOSUCCINIC ACID; CHLORIDE INTOXICATION; AGENTS; TODDLERS; HEALTH
AB Succimer lowers blood lead concentrations in children, and the structure of succimer chelates of lead and cadmium are similar. Using blood samples from a randomized trial of succimer for lead poisoning, however, we found that succimer did not lower blood cadmium in children with background exposure.
C1 [Cao, Yang; Bottai, Matteo] Karolinska Inst, Inst Environm Med, Div Epidemiol, Unit Biostat, S-10401 Stockholm, Sweden.
[Chen, Aimin] Univ Cincinnati, Coll Med, Dept Environm Hlth, Div Epidemiol & Biostat, Cincinnati, OH 45267 USA.
[Caldwell, Kathleen L.] Ctr Dis Control & Prevent, Inorgan & Radiat Analyt Toxicol Branch, Atlanta, GA USA.
[Rogan, Walter J.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
RP Rogan, WJ (reprint author), NIEHS, Epidemiol Branch, POB 12233,Mail Drop A3-05,Fedex UPS 111 TW Alexan, Res Triangle Pk, NC 27709 USA.
EM rogan@niehs.nih.gov
RI Rogan, Walter/I-6034-2012;
OI Rogan, Walter/0000-0002-9302-0160; Cao, Yang/0000-0002-3552-9153
FU National Institutes of Health, National Institute of Environmental
Health Sciences
FX Supported in part by the Intramural Research Program of the National
Institutes of Health, National Institute of Environmental Health
Sciences. The contents are solely the responsibility of the authors and
do not necessarily represent the official views of the CDC. The authors
declare no conflicts of interest.
NR 22
TC 1
Z9 1
U1 1
U2 4
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3476
J9 J PEDIATR-US
JI J. Pediatr.
PD AUG
PY 2013
VL 163
IS 2
BP 598
EP 600
DI 10.1016/j.jpeds.2013.03.009
PG 3
WC Pediatrics
SC Pediatrics
GA 198YG
UT WOS:000322959500058
PM 23601497
ER
PT J
AU Wang, YN
Collins, J
Holland, RJ
Keefer, LK
Ivanic, J
AF Wang, Yan-Ni
Collins, Jack
Holland, Ryan J.
Keefer, Larry K.
Ivanic, Joseph
TI Decoding Nitric Oxide Release Rates of Amine-Based Diazeniumdiolates
SO JOURNAL OF PHYSICAL CHEMISTRY A
LA English
DT Article
ID DIRECT CONFIGURATION-INTERACTION; DENSITY-FUNCTIONAL THEORY;
PERTURBATION-THEORY; MCSCF THEORY; BASIS-SETS; OPEN-SHELL; IN-VITRO; NO;
GENERATION; CHEMISTRY
AB Amine-based diazeniumdiolates (NONOates) have garnered widespread use as nitric oxide (NO) donors, and their potential for nitroxyl (HNO) release has more recently been realized. While NO release rates can vary significantly with the type of amine, half-lives of seconds to days under physiological conditions, there is as yet no way to determine a priori the NO or HNO production rates of a given species, and no discernible trends have manifested other than that secondary amines produce only NO (i.e., no HNO). As a step to understanding these complex systems, here we describe a procedure for modeling amine-based NONOates in water solvent that provides an excellent correlation (R-2 = 0.94) between experimentally measured dissociation rates of seven secondary amine species and their computed NO release activation energies. The significant difference in behavior of NONOates in the gas and solvent phases is also rigorously demonstrated via explicit additions of quantum mechanical water molecules. The presented results suggest that the as-yet unsynthesized simplest amine-based NONOate, the diazeniumdiolated ammonia anion [H2N N(O)=NO-], could serve as an unperturbed HNO donor. These results provide a step forward toward the accurate modeling of general NO and/or HNO donors as well as for the identification of tailored prodrug candidates.
C1 [Wang, Yan-Ni; Collins, Jack; Ivanic, Joseph] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Informat Syst Program, Adv Biomed Comp Ctr, Frederick, MD 21702 USA.
[Holland, Ryan J.; Keefer, Larry K.] NCI, Drug Design Sect, Biol Chem Lab, Frederick, MD 21702 USA.
RP Ivanic, J (reprint author), SAIC Frederick Inc, Frederick Natl Lab Canc Res, Informat Syst Program, Adv Biomed Comp Ctr, Frederick, MD 21702 USA.
EM ivanicj@mail.nih.gov
RI Keefer, Larry/N-3247-2014
OI Keefer, Larry/0000-0001-7489-9555
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; Intramural Research Program of the NIH, National
Cancer Institute, Center for Cancer Research
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
Contract No. HHSN261200800001E, and by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research. The
content of this publication does not necessarily reflect the views or
policies of the Department of Health and Human Services, nor does
mention of trade names, commercial products, or organizations imply
endorsement by the U.S. Government.
NR 50
TC 4
Z9 4
U1 0
U2 13
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1089-5639
J9 J PHYS CHEM A
JI J. Phys. Chem. A
PD AUG 1
PY 2013
VL 117
IS 30
BP 6671
EP 6677
DI 10.1021/jp404589p
PG 7
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 196WE
UT WOS:000322807300027
PM 23834533
ER
PT J
AU Menendez, D
Nguyen, TA
Freudenberg, JM
Mathew, VJ
Anderson, CW
Jothi, R
Resnick, MA
AF Menendez, Daniel
Thuy-Ai Nguyen
Freudenberg, Johannes M.
Mathew, Viju J.
Anderson, Carl W.
Jothi, Raja
Resnick, Michael A.
TI Diverse stresses dramatically alter genome-wide p53 binding and
transactivation landscape in human cancer cells
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID EMBRYONIC STEM-CELLS; TUMOR-SUPPRESSOR; DNA RECOGNITION; TRANSCRIPTIONAL
NETWORK; P53-BINDING SITES; RESPONSE ELEMENT; GENE; MUTATIONS; PROMOTER;
PROTEIN
AB The effects of diverse stresses on promoter selectivity and transcription regulation by the tumor suppressor p53 are poorly understood. We have taken a comprehensive approach to characterizing the human p53 network that includes p53 levels, binding, expression and chromatin changes under diverse stresses. Human osteosarcoma U2OS cells treated with anti-cancer drugs Doxorubicin (DXR) or Nutlin-3 (Nutlin) led to strikingly different p53 gene binding patterns based on chromatin immunoprecipitation with high-throughput sequencing experiments. Although two contiguous RRRCWWGYYY decamers is the consensus binding motif, p53 can bind a single decamer and function in vivo. Although the number of sites bound by p53 was six times greater for Nutlin than DXR, expression changes induced by Nutlin were much less dramatic compared with DXR. Unexpectedly, the solvent dimethylsulphoxide (DMSO) alone induced p53 binding to many sites common to DXR; however, this binding had no effect on target gene expression. Together, these data imply a two-stage mechanism for p53 transactivation where p53 binding only constitutes the first stage. Furthermore, both p53 binding and transactivation were associated with increased active histone modification histone H3 lysine 4 trimethylation. We discovered 149 putative new p53 target genes including several that are relevant to tumor suppression, revealing potential new targets for cancer therapy and expanding our understanding of the p53 regulatory network.
C1 [Menendez, Daniel; Thuy-Ai Nguyen; Anderson, Carl W.; Resnick, Michael A.] NIEHS, Chromosome Stabil Grp, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Freudenberg, Johannes M.; Mathew, Viju J.; Jothi, Raja] NIEHS, Syst Biol Grp, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Mathew, Viju J.] William G Enloe High Sch, Raleigh, NC 27610 USA.
[Anderson, Carl W.] Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA.
RP Jothi, R (reprint author), NIEHS, Syst Biol Grp, Mol Carcinogenesis Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM jothi@mail.nih.gov; resnick@niehs.nih.gov
RI Jothi, Raja/G-3780-2015
FU NIH, National Institute of Environmental Health Sciences [Z01-ES065079,
1ZIAES102625-04]
FX Funding for open access charge: Supported by the Intramural Research
Program of the NIH, National Institute of Environmental Health Sciences
[Z01-ES065079 to M. A. R., 1ZIAES102625-04 to R.J.].
NR 68
TC 52
Z9 52
U1 0
U2 11
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 AUG
PY 2013
VL 41
IS 15
BP 7286
EP 7301
DI 10.1093/nar/gkt504
PG 16
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 212GL
UT WOS:000323970700017
PM 23775793
ER
PT J
AU Marinotti, O
Cerqueira, GC
de Almeida, LGP
Ferro, MIT
Loreto, ELD
Zaha, A
Teixeira, SMR
Wespiser, AR
Silva, AAE
Schlindwein, AD
Pacheco, ACL
da Silva, ALD
Graveley, BR
Walenz, BP
Lima, BD
Ribeiro, CAG
Nunes-Silva, CG
de Carvalho, CR
Soares, CMD
de Menezes, CBA
Matiolli, C
Caffrey, D
Araujo, DAM
de Oliveira, DM
Golenbock, D
Grisard, EC
Fantinatti-Garboggini, F
de Carvalho, FM
Barcellos, FG
Prosdocimi, F
May, G
de Azevedo, GM
Guimaraes, GM
Goldman, GH
Padilha, IQM
Batista, JD
Ferro, JA
Ribeiro, JMC
Fietto, JLR
Dabbas, KM
Cerdeira, L
Agnez-Lima, LF
Brocchi, M
de Carvalho, MO
Teixeira, MD
Maia, MDD
Goldman, MHS
Cruz Schneider, MPC
Felipe, MSS
Hungria, M
Nicolas, MF
Pereira, M
Montes, MA
Cantao, ME
Vincentz, M
Rafael, MS
Silverman, N
Stoco, PH
Souza, RC
Vicentini, R
Gazzinelli, RT
Neves, RD
Silva, R
Astolfi, S
Maciel, TEF
Urmenyi, TP
Tadei, WP
Camargo, EP
de Vasconcelos, ATR
AF Marinotti, Osvaldo
Cerqueira, Gustavo C.
Paula de Almeida, Luiz Gonzaga
Tiraboschi Ferro, Maria Ines
da Silva Loreto, Elgion Lucio
Zaha, Arnaldo
Teixeira, Santuza M. R.
Wespiser, Adam R.
Almeida e Silva, Alexandre
Schlindwein, Aline Daiane
Landim Pacheco, Ana Carolina
da Costa da Silva, Artur Luiz
Graveley, Brenton R.
Walenz, Brian P.
Lima, Bruna de Araujo
Gomes Ribeiro, Carlos Alexandre
Nunes-Silva, Carlos Gustavo
de Carvalho, Carlos Roberto
de Almeida Soares, Celia Maria
Afonso de Menezes, Claudia Beatriz
Matiolli, Cleverson
Caffrey, Daniel
Araujo, Demetrius Antonio M.
de Oliveira, Diana Magalhaes
Golenbock, Douglas
Grisard, Edmundo Carlos
Fantinatti-Garboggini, Fabiana
de Carvalho, Fabiola Marques
Barcellos, Fernando Gomes
Prosdocimi, Francisco
May, Gemma
de Azevedo Junior, Gilson Martins
Guimaraes, Giselle Moura
Goldman, Gustavo Henrique
Padilha, Itacio Q. M.
Batista, Jacqueline da Silva
Ferro, Jesus Aparecido
Ribeiro, Jose M. C.
Rangel Fietto, Juliana Lopes
Dabbas, Karina Maia
Cerdeira, Louise
Agnez-Lima, Lucymara Fassarella
Brocchi, Marcelo
de Carvalho, Marcos Oliveira
Teixeira, Marcus de Melo
Diniz Maia, Maria de Mascena
Goldman, Maria Helena S.
Cruz Schneider, Maria Paula
Soares Felipe, Maria Sueli
Hungria, Mariangela
Nicolas, Marisa Fabiana
Pereira, Maristela
Montes, Martin Alejandro
Cantao, Mauricio E.
Vincentz, Michel
Rafael, Miriam Silva
Silverman, Neal
Stoco, Patricia Hermes
Souza, Rangel Celso
Vicentini, Renato
Gazzinelli, Ricardo Tostes
Neves, Rogerio de Oliveira
Silva, Rosane
Astolfi-Filho, Spartaco
Ferreira Maciel, Talles Eduardo
Urmenyi, Turan P.
Tadei, Wanderli Pedro
Camargo, Erney Plessmann
de Vasconcelos, Ana Tereza Ribeiro
TI The Genome of Anopheles darlingi, the main neotropical malaria vector
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID SINGLE-NUCLEOTIDE POLYMORPHISMS; MOSQUITO AEDES-AEGYPTI; DNA
FLOW-CYTOMETRY; BRAZILIAN AMAZON; ODORANT-BINDING; SOUTH-AMERICA;
LABORATORY COLONIZATION; INSECTICIDE RESISTANCE; CULEX-QUINQUEFASCIATUS;
CHEMOSENSORY RECEPTORS
AB Anopheles darlingi is the principal neotropical malaria vector, responsible for more than a million cases of malaria per year on the American continent. Anopheles darlingi diverged from the African and Asian malaria vectors similar to 100 million years ago (mya) and successfully adapted to the New World environment. Here we present an annotated reference A. darlingi genome, sequenced from a wild population of males and females collected in the Brazilian Amazon. A total of 10 481 predicted protein-coding genes were annotated, 72% of which have their closest counterpart in Anopheles gambiae and 21% have highest similarity with other mosquito species. In spite of a long period of divergent evolution, conserved gene synteny was observed between A. darlingi and A. gambiae. More than 10 million single nucleotide polymorphisms and short indels with potential use as genetic markers were identified. Transposable elements correspond to 2.3% of the A. darlingi genome. Genes associated with hematophagy, immunity and insecticide resistance, directly involved in vector-human and vector-parasite interactions, were identified and discussed. This study represents the first effort to sequence the genome of a neotropical malaria vector, and opens a new window through which we can contemplate the evolutionary history of anopheline mosquitoes. It also provides valuable information that may lead to novel strategies to reduce malaria transmission on the South American continent. The A. darlingi genome is accessible at www.labinfo.lncc.br/index.php/anopheles-darlingi.
C1 [Marinotti, Osvaldo] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA.
[Cerqueira, Gustavo C.] Broad Inst Harvard & Massachusetts, Inst Technol, Cambridge, MA 02141 USA.
[Paula de Almeida, Luiz Gonzaga; de Carvalho, Fabiola Marques; Cerdeira, Louise; Nicolas, Marisa Fabiana; Cantao, Mauricio E.; Souza, Rangel Celso; de Vasconcelos, Ana Tereza Ribeiro] Lab Bioinformat Lab Nacl Computacao Cientif, BR-25651075 Petropolis, RJ, Brazil.
[Tiraboschi Ferro, Maria Ines; Ferro, Jesus Aparecido; Dabbas, Karina Maia] Univ Estadual Paulista, Dept Tecnol, Fac Ciencias Agrarias & Vet Jaboticabal, BR-14884900 Sao Paulo, SP, Brazil.
[da Silva Loreto, Elgion Lucio] Univ Fed Santa Maria, Dept Biol, BR-97105900 Santa Maria, RS, Brazil.
[Zaha, Arnaldo] Univ Fed Rio Grande do Sul, Dept Biol Mol & Biotecnol, Ctr Biotecnol, BR-91501970 Porto Alegre, RS, Brazil.
[Teixeira, Santuza M. R.] Univ Fed Minas Gerais, Dept Bioquim & Imunol, BR-31270901 Belo Horizonte, MG, Brazil.
[Wespiser, Adam R.; Caffrey, Daniel; Golenbock, Douglas; Silverman, Neal] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA.
[Almeida e Silva, Alexandre] Lab Entomol Med IPEPATRO FIOCRUZ, BR-76812245 Porto Velho, Brazil.
[Schlindwein, Aline Daiane; Grisard, Edmundo Carlos; Stoco, Patricia Hermes] Univ Fed Santa Catarina, Dept Microbiol Imunol & Parasitol, BR-88040900 Florianopolis, SC, Brazil.
[Landim Pacheco, Ana Carolina; de Oliveira, Diana Magalhaes] Univ Estadual Ceara, Ctr Ciencias Saude, BR-62042280 Fortaleza, Ceara, Brazil.
[Landim Pacheco, Ana Carolina] Univ Fed Piaui, Dept Ciencias Biol, BR-60740000 Picos, Brazil.
[da Costa da Silva, Artur Luiz; May, Gemma] Fed Univ Para, Inst Ciencias Biol, Dept Genet, BR-66075900 Belem, Para, Brazil.
[Graveley, Brenton R.] Univ Connecticut, Ctr Hlth, Dept Genet & Dev Biol, Farmington, CT 06030 USA.
[Walenz, Brian P.; Brocchi, Marcelo] J Craig Venter Inst, Rockville, MD 20850 USA.
[Lima, Bruna de Araujo] Univ Estadual Campinas, Inst Biol, Dept Genet Evolucao & Bioagentes, BR-13083862 Campinas, SP, Brazil.
[Gomes Ribeiro, Carlos Alexandre; Neves, Rogerio de Oliveira; Astolfi-Filho, Spartaco] Univ Fed Vicosa, Dept Genet Melhoramento, BR-36570000 Vicosa, MG, Brazil.
[Nunes-Silva, Carlos Gustavo] Univ Fed Amazonas, Ctr Apoio Multidisciplinar, BR-69077000 Manaus, Amazonas, Brazil.
[de Carvalho, Carlos Roberto; Pereira, Maristela] Univ Fed Vicosa, Dept Biol Geral, BR-36571000 Vicosa, MG, Brazil.
[de Almeida Soares, Celia Maria] Univ Fed Goias, Inst Ciencias Biol, Mol Biol Lab, BR-74001970 Goiania, Go, Brazil.
[Afonso de Menezes, Claudia Beatriz; Fantinatti-Garboggini, Fabiana; Padilha, Itacio Q. M.] Univ Estadual Campinas, Ctr Pluridisciplinar Pesquisas Quim Biol & Agr, Div Recursos Microbianos, BR-13140000 Paulinia, SP, Brazil.
[Matiolli, Cleverson] Univ Estadual Campinas, Ctr Biol Mol & Engn Genet, BR-13083875 Campinas, SP, Brazil.
[Araujo, Demetrius Antonio M.] Univ Fed Paraiba, Dept Biotechnol, BR-58051900 Joao Pessoa, Paraiba, Brazil.
[Barcellos, Fernando Gomes] Univ Estadual Londrina, Dept Biol Geral, BR-86055990 Londrina, PR, Brazil.
[Prosdocimi, Francisco] Univ Fed Rio de Janeiro, Inst Bioquim Med, BR-21941902 Rio De Janeiro, RJ, Brazil.
[de Azevedo Junior, Gilson Martins; Guimaraes, Giselle Moura] Inst Nacl de Pesquisas da Amazonia, Programa Grad Genet, BR-69067375 Manaus, Amazonas, Brazil.
[Goldman, Gustavo Henrique] Lab Nacl Ciencia & Tecnol Bioetanol CTBE, BR-13083970 Sao Paulo, SP, Brazil.
[Goldman, Gustavo Henrique] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Ciencias Farmaceut, BR-14040903 Ribeirao Preto, SP, Brazil.
[Batista, Jacqueline da Silva] Inst Nacl de Pesquisas da Amazonia, Lab Temat Biol Mol, Coordenacoa Biodiversidade, BR-69060001 Manaus, Amazonas, Brazil.
[Ribeiro, Jose M. C.] NIH, NIAID, Lab Malaria & Vector Res, Bethesda, MD 20817 USA.
[Rangel Fietto, Juliana Lopes; Ferreira Maciel, Talles Eduardo] Univ Fed Vicosa, Dept Bioquim & Biol Mol, BR-36570000 Vicosa, MG, Brazil.
[Agnez-Lima, Lucymara Fassarella] Univ Fed Rio Grande do Norte, Dept Biol Celular & Genet, BR-59072970 Natal, RN, Brazil.
[de Carvalho, Marcos Oliveira] Univ Fed Rio Grande do Sul, Inst Biociencias, Programa PosGrad Genet & Biol Mol, BR-90150197 Porto Alegre, RS, Brazil.
[Teixeira, Marcus de Melo; Soares Felipe, Maria Sueli] Univ Brasilia, Dept Biol Celular, Inst Ciencias Biol, BR-70910900 Brasilia, DF, Brazil.
[Goldman, Maria Helena S.] Univ Fed Rural Pernambuco, Dept Biol, BR-50740520 Recife, PE, Brazil.
[Goldman, Maria Helena S.] Univ Sao Paulo, Dept Biol, Fac Filosofia Ciencias & Letras Ribeirao Preto, BR-14040901 Ribeirao Preto, SP, Brazil.
[Cruz Schneider, Maria Paula] Fed Univ Para, Inst Ciencias Biol, BR-66075970 Belem, Para, Brazil.
[Soares Felipe, Maria Sueli] Univ Catolica Brasilia, Programa PosGrad Ciencias Genom & Biotecnol, Brasilia, DF, Brazil.
[Hungria, Mariangela] Empresa Brasileira Pesquisa Agropecuaria Soja, BR-86001970 Londrina, PR, Brazil.
[Cantao, Mauricio E.] CNPSA, Empresa Brasileira Pesquisa Agropecuaria, BR-89700000 Concordia, SC, Brazil.
[Vincentz, Michel] Univ Estadual Campinas, Dept Biol Vegetal, BR-13083970 Campinas, SP, Brazil.
[Rafael, Miriam Silva; Tadei, Wanderli Pedro] Inst Nacl de Pesquisas da Amazonia, Lab Vetores Malaria & Dengue, BR-69067375 Manaus, Amazonas, Brazil.
[Vicentini, Renato] Univ Estadual Campinas, Lab Bioinformat & Biol Sistemas, BR-13083875 Campinas, SP, Brazil.
[Gazzinelli, Ricardo Tostes] Univ Fed Minas Gerais, Dept Bioquim & Imunol, BR-31270901 Belo Horizonte, MG, Brazil.
[Silva, Rosane; Urmenyi, Turan P.] Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, BR-21941902 Rio De Janeiro, Brazil.
[Camargo, Erney Plessmann] Univ Sao Paulo, Inst Ciencias Biomed, Dept Parasitol, BR-05508000 Sao Paulo, SP, Brazil.
RP Marinotti, O (reprint author), Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA.
EM omarinot@uci.edu; atrv@lncc.br
RI Goldman, Gustavo/F-1848-2013; Vicentini, Renato/C-5967-2012; Camargo,
Erney/A-6765-2009; Barcellos, Fernando/B-7948-2014; Silva,
Artur/E-1474-2014; de Araujo Lima, Bruna/A-5961-2013; Agnez-Lima,
Lucymara/F-9655-2012; Soares, Celia/N-6395-2014; Grisard,
Edmundo/A-7338-2015; Cerdeira, Louise/C-3749-2013; Padilha,
Itacio/D-9734-2013; Brocchi, Marcelo/E-3723-2012; Araujo,
Demetrius/N-8441-2014; Ribeiro, Jose/J-7011-2015; Ferro,
Jesus/C-8251-2013; Silva, Alexandre/A-6768-2008; Fantinatti-Garboggini,
Fabiana/F-3991-2012; Prosdocimi, Francisco/F-6847-2012; Vasconcelos, Ana
Tereza/I-1011-2012; Goldman, Maria Helena/D-1424-2012
OI Agnez-Lima, Lucymara/0000-0003-0642-3162; Grisard,
Edmundo/0000-0001-8916-8296; Camargo, Erney/0000-0003-0011-5871; Nunes
da Silva, Carlos Gustavo/0000-0003-2276-838X; Marinotti,
Osvaldo/0000-0002-7173-7160; Silverman, Neal/0000-0002-4259-456X;
Ribeiro, Jose/0000-0002-9107-0818; Ferro, Jesus/0000-0002-3966-1303;
Prosdocimi, Francisco/0000-0002-6761-3069; Vasconcelos, Ana
Tereza/0000-0002-4632-2086; Graveley, Brenton/0000-0001-5777-5892;
Goldman, Maria Helena/0000-0002-6786-9320
FU Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq);
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health (USA); Laboratorio de
Bioinformatica - Laboratorio Nacional de Computacao Cientifica (LNCC)
FX Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq);
the Intramural Research Program of the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health (USA) (to J.M.C.R)-J.M.C.R. is a government
employee and this is a government work, the work is in the public domain
in the USA. Notwithstanding any other agreements, the NIH reserves the
right to provide the work to PubMedCentral for display and use by the
public, and PubMedCentral may tag or modify the work consistent with its
customary practices. You can establish rights outside of the USA subject
to a government use license; National Institute of General Medical
Science, National Institutes of Health (USA) [2R01GM077117-04A1 to B. P.
W]. Funding for open access charge: Laboratorio de Bioinformatica -
Laboratorio Nacional de Computacao Cientifica (LNCC).
NR 104
TC 37
Z9 44
U1 1
U2 38
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD AUG
PY 2013
VL 41
IS 15
BP 7387
EP 7400
DI 10.1093/nar/gkt484
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 212GL
UT WOS:000323970700025
PM 23761445
ER
PT J
AU Panja, S
Schu, DJ
Woodson, SA
AF Panja, Subrata
Schu, Daniel J.
Woodson, Sarah A.
TI Conserved arginines on the rim of Hfq catalyze base pair formation and
exchange
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID ESCHERICHIA-COLI HFQ; SM-LIKE PROTEIN; HELIX-COIL TRANSITION; RNA
CHAPERONE HFQ; C-TERMINAL DOMAIN; MESSENGER-RNA; SOLUBLE-RNA; DSRA RNA;
TRANSLATION INITIATION; HOST FACTOR
AB The Sm-like protein Hfq is required for gene regulation by small RNAs (sRNAs) in bacteria and facilitates base pairing between sRNAs and their mRNA targets. The proximal and distal faces of the Hfq hexamer specifically bind sRNA and mRNA targets, but they do not explain how Hfq accelerates the formation and exchange of RNA base pairs. Here, we show that conserved arginines on the outer rim of the hexamer that are known to interact with sRNA bodies are required for Hfq's chaperone activity. Mutations in the arginine patch lower the ability of Hfq to act in sRNA regulation of rpoS translation and eliminate annealing of natural sRNAs or unstructured oligonucleotides, without preventing binding to either the proximal or distal face. Stopped-flow FRET and fluorescence anisotropy show that complementary RNAs transiently form a ternary complex with Hfq, but the RNAs are not released as a double helix in the absence of rim arginines. RNAs bound to either face of Hfq quench the fluorescence of a tryptophan adjacent to the arginine patch, demonstrating that the rim can simultaneously engage two RNA strands. We propose that the arginine patch overcomes entropic and electrostatic barriers to helix nucleation and constitutes the active site for Hfq's chaperone function.
C1 [Panja, Subrata; Woodson, Sarah A.] Johns Hopkins Univ, TC Jenkins Dept Biophys, Baltimore, MD 21218 USA.
[Schu, Daniel J.] NCI, Mol Biol Lab, Bethesda, MD 20892 USA.
RP Woodson, SA (reprint author), Johns Hopkins Univ, TC Jenkins Dept Biophys, 3400 N Charles St, Baltimore, MD 21218 USA.
EM swoodson@jhu.edu
OI Woodson, Sarah/0000-0003-0170-1987
FU National Institute of General Medicine [R01 GM46686]; intramural
research program of the National Cancer Institute; National Institutes
of Health
FX National Institute of General Medicine [R01 GM46686 to S. W.] and the
intramural research program of the National Cancer Institute [to
D.J.S.]. Funding for open access charge: National Institutes of Health.
NR 67
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U1 1
U2 14
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD AUG
PY 2013
VL 41
IS 15
BP 7536
EP 7546
DI 10.1093/nar/gkt521
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 212GL
UT WOS:000323970700037
PM 23771143
ER
PT J
AU Sanchez, R
Silberstein, LE
Lindblad, RW
Welniak, LA
Mondoro, H
Wagner, JE
AF Sanchez, Rosa
Silberstein, Leslie E.
Lindblad, Robert W.
Welniak, Lisbeth A.
Mondoro, Heath
Wagner, John E.
TI Strategies for More Rapid Translation of Cellular Therapies for
Children: A US Perspective
SO PEDIATRICS
LA English
DT Article
DE pediatric clinical trials; stem cell; cell therapy
ID GENE-THERAPY; BETA-THALASSEMIA; CLINICAL-TRIALS; TRANSPLANTATION;
ADRENOLEUKODYSTROPHY
AB Clinical trials for pediatric diseases face many challenges, including trial design, accrual, ethical considerations for children as research subjects, and the cost of long-term follow-up studies. In September 2011, the Production Assistance for Cellular Therapies Program, funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health, sponsored a workshop, "Cell Therapy for Pediatric Diseases: A Growing Frontier," with the overarching goal of optimizing the path of discovery in research involving novel cellular therapeutic interventions for debilitating pediatric conditions with few or no available treatment options. Academic and industry investigators in the fields of cellular therapy and regenerative medicine described the obstacles encountered in conducting a clinical trial from concept to conclusion. Patient and parent advocates, bioethicists, biostatisticians, regulatory representatives from the US Food and Drug Administration, and translational scientists actively participated in this workshop, seeking to identify the unmet needs specific to cellular therapies and treatment of pediatric diseases and propose strategies to facilitate the development of novel therapies. In this article we summarize the obstacles and potential corrective strategies identified by workshop participants to maximize the speed of cell therapy translational research for childhood diseases.
C1 [Sanchez, Rosa] Blood Syst Res Inst, San Francisco, CA USA.
[Silberstein, Leslie E.] Ctr Human Cell Therapy, Boston, MA USA.
[Lindblad, Robert W.] EMMES Corp, Rockville, MD USA.
[Welniak, Lisbeth A.; Mondoro, Heath] NHLBI, Div Blood Dis & Resources, Bethesda, MD 20892 USA.
[Wagner, John E.] Univ Minnesota, Blood & Marrow Transplantat Program, Minneapolis, MN USA.
RP Sanchez, R (reprint author), POB 6177, Alameda, CA 94501 USA.
EM rosasanchez.rosen@gmail.com
FU National Heart, Lung, and Blood Institute (NHLBI) [K07 HL088923, N01
HB07197, N01 HB07198, N01 HB 07200]; National Institutes of Health
FX Supported in part by National Heart, Lung, and Blood Institute (NHLBI)
grant K07 HL088923 (Sanchez) and NHLBI contracts N01 HB07197 (Lindblad),
N01 HB07198 (Silberstein), and N01 HB 07200 (Wagner). Funded by the
National Institutes of Health.
NR 18
TC 3
Z9 3
U1 1
U2 12
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
J9 PEDIATRICS
JI Pediatrics
PD AUG
PY 2013
VL 132
IS 2
BP 351
EP 358
DI 10.1542/peds.2012-3383
PG 8
WC Pediatrics
SC Pediatrics
GA 198XN
UT WOS:000322957300059
PM 23837178
ER
PT J
AU Ballew, BJ
Joseph, V
De, S
Sarek, G
Vannier, JB
Stracker, T
Schrader, KA
Small, TN
O'Reilly, R
Manschreck, C
Fleischut, MMH
Zhang, LY
Sullivan, J
Stratton, K
Yeager, M
Jacobs, K
Giri, N
Alter, BP
Boland, J
Burdett, L
Offit, K
Boulton, SJ
Savage, SA
Petrini, JHJ
AF Ballew, Bari J.
Joseph, Vijai
De, Saurav
Sarek, Grzegorz
Vannier, Jean-Baptiste
Stracker, Travis
Schrader, Kasmintan A.
Small, Trudy N.
O'Reilly, Richard
Manschreck, Chris
Fleischut, Megan M. Harlan
Zhang, Liying
Sullivan, John
Stratton, Kelly
Yeager, Meredith
Jacobs, Kevin
Giri, Neelam
Alter, Blanche P.
Boland, Joseph
Burdett, Laurie
Offit, Kenneth
Boulton, Simon J.
Savage, Sharon A.
Petrini, John H. J.
TI A Recessive Founder Mutation in Regulator of Telomere Elongation
Helicase 1, RTEL1, Underlies Severe Immunodeficiency and Features of
Hoyeraal Hreidarsson Syndrome
SO PLOS GENETICS
LA English
DT Article
ID DYSKERATOSIS-CONGENITA; T-LOOPS; DNA; PROTEIN; LENGTH; SUSCEPTIBILITY;
RECOMBINATION; STABILITY; VARIANTS; CIRCLES
AB Dyskeratosis congenita (DC) is a heterogeneous inherited bone marrow failure and cancer predisposition syndrome in which germline mutations in telomere biology genes account for approximately one-half of known families. Hoyeraal Hreidarsson syndrome (HH) is a clinically severe variant of DC in which patients also have cerebellar hypoplasia and may present with severe immunodeficiency and enteropathy. We discovered a germline autosomal recessive mutation in RTEL1, a helicase with critical telomeric functions, in two unrelated families of Ashkenazi Jewish (AJ) ancestry. The affected individuals in these families are homozygous for the same mutation, R1264H, which affects three isoforms of RTEL1. Each parent was a heterozygous carrier of one mutant allele. Patient-derived cell lines revealed evidence of telomere dysfunction, including significantly decreased telomere length, telomere length heterogeneity, and the presence of extra-chromosomal circular telomeric DNA. In addition, RTEL1 mutant cells exhibited enhanced sensitivity to the interstrand cross-linking agent mitomycin C. The molecular data and the patterns of inheritance are consistent with a hypomorphic mutation in RTEL1 as the underlying basis of the clinical and cellular phenotypes. This study further implicates RTEL1 in the etiology of DC/HH and immunodeficiency, and identifies the first known homozygous autosomal recessive disease-associated mutation in RTEL1.
C1 [Ballew, Bari J.; Giri, Neelam; Alter, Blanche P.; Savage, Sharon A.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Joseph, Vijai; Schrader, Kasmintan A.; Manschreck, Chris; Fleischut, Megan M. Harlan; Sullivan, John; Stratton, Kelly; Offit, Kenneth] Mem Hosp, Mem Sloan Kettering Canc Ctr, Clin Genet Serv, Dept Med, New York, NY USA.
[De, Saurav; Stracker, Travis; Petrini, John H. J.] Mem Sloan Kettering Canc Ctr, Program Mol Biol, Sloan Kettering Inst, New York, NY 10021 USA.
[Small, Trudy N.; O'Reilly, Richard] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA.
[Zhang, Liying] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA.
[Yeager, Meredith; Jacobs, Kevin; Boland, Joseph; Burdett, Laurie] SAIC Frederick Inc, Canc Genom Res Lab, NCI Frederick, Frederick, MD USA.
[Offit, Kenneth] Mem Sloan Kettering Canc Ctr, Canc Genet & Biol Program, Sloan Kettering Inst, New York, NY 10021 USA.
RP Ballew, BJ (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD USA.
EM savagesh@mail.nih.gov; petrinij@mskcc.org
RI Stracker, Travis/I-2815-2015; Savage, Sharon/B-9747-2015;
OI Stracker, Travis/0000-0002-8650-2081; Savage,
Sharon/0000-0001-6006-0740; Joseph, Vijai/0000-0002-7933-151X
FU Division of Cancer Epidemiology and Genetics, National Cancer Institute,
National Institutes of Health; Westat, Incorporated [N02-CP-91026,
N02-CP-11019, HHSN261200655001C]; Geoffrey Beene Cancer Research Fund;
Sharon Levine Corzine Research Fund; Esther & Hyman Rapport
Philanthropic Trust; Taub Family Cancer Research Fund; Cancer Research
UK; ERC; EMBO LT fellowships; Starr Cancer Consortium; [GM56888]
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 (SAS, BJB, BPA, NG), and by contracts N02-CP-91026,
N02-CP-11019 and HHSN261200655001C with Westat, Incorporated, as well as
the Geoffrey Beene Cancer Research Fund, The Sharon Levine Corzine
Research Fund, the Esther & Hyman Rapport Philanthropic Trust, and Taub
Family Cancer Research Fund. The lab of SJB was funded by Cancer
Research UK and an ERC advanced investigator grant (RecMitMei). SJB was
a Royal Society Wolfson Research Merit Award holder. GS and JBV were
funded by EMBO LT fellowships. This work was also supported by GM56888
and The Starr Cancer Consortium (JHJP). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 38
TC 38
Z9 40
U1 0
U2 8
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 AUG
PY 2013
VL 9
IS 8
AR e1003695
DI 10.1371/journal.pgen.1003695
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 210KB
UT WOS:000323830300046
PM 24009516
ER
PT J
AU Liu, CT
Monda, KL
Taylor, KC
Lange, L
Demerath, EW
Palmas, W
Wojczynski, MK
Ellis, JC
Vitolins, MZ
Liu, SM
Papanicolaou, GJ
Irvin, MR
Xue, LT
Griffin, PJ
Nalls, MA
Adeyemo, A
Liu, JK
Li, G
Ruiz-Narvaez, EA
Chen, WM
Chen, F
Henderson, BE
Millikan, RC
Ambrosone, CB
Strom, SS
Guo, XQ
Andrews, JS
Sun, YV
Mosley, TH
Yanek, LR
Shriner, D
Haritunians, T
Rotter, JI
Speliotes, EK
Smith, M
Rosenberg, L
Mychaleckyj, J
Nayak, U
Spruill, I
Garvey, WT
Pettaway, C
Nyante, S
Bandera, EV
Britton, AF
Zonderman, AB
Rasmussen-Torvik, LJ
Chen, YDI
Ding, J
Lohman, K
Kritchevsky, SB
Zhao, W
Peyser, PA
Kardia, SLR
Kabagambe, E
Broeckel, U
Chen, GJ
Zhou, J
Wassertheil-Smoller, S
Neuhouser, ML
Rampersaud, E
Psaty, B
Kooperberg, C
Manson, JE
Kuller, LH
Ochs-Balcom, HM
Johnson, KC
Sucheston, L
Ordovas, JM
Palmer, JR
Haiman, CA
McKnight, B
Howard, BV
Becker, DM
Bielak, LF
Liu, YM
Allison, MA
Grant, SFA
Burke, GL
Patel, SR
Schreiner, PJ
Borecki, IB
Evans, MK
Taylor, H
Sale, MM
Howard, V
Carlson, CS
Rotimi, CN
Cushman, M
Harris, TB
Reiner, AP
Cupples, LA
North, KE
Fox, CS
AF Liu, Ching-Ti
Monda, Keri L.
Taylor, Kira C.
Lange, Leslie
Demerath, Ellen W.
Palmas, Walter
Wojczynski, Mary K.
Ellis, Jaclyn C.
Vitolins, Mara Z.
Liu, Simin
Papanicolaou, George J.
Irvin, Marguerite R.
Xue, Luting
Griffin, Paula J.
Nalls, Michael A.
Adeyemo, Adebowale
Liu, Jiankang
Li, Guo
Ruiz-Narvaez, Edward A.
Chen, Wei-Min
Chen, Fang
Henderson, Brian E.
Millikan, Robert C.
Ambrosone, Christine B.
Strom, Sara S.
Guo, Xiuqing
Andrews, Jeanette S.
Sun, Yan V.
Mosley, Thomas H.
Yanek, Lisa R.
Shriner, Daniel
Haritunians, Talin
Rotter, Jerome I.
Speliotes, Elizabeth K.
Smith, Megan
Rosenberg, Lynn
Mychaleckyj, Josyf
Nayak, Uma
Spruill, Ida
Garvey, W. Timothy
Pettaway, Curtis
Nyante, Sarah
Bandera, Elisa V.
Britton, Angela F.
Zonderman, Alan B.
Rasmussen-Torvik, Laura J.
Chen, Yii-Der Ida
Ding, Jingzhong
Lohman, Kurt
Kritchevsky, Stephen B.
Zhao, Wei
Peyser, Patricia A.
Kardia, Sharon L. R.
Kabagambe, Edmond
Broeckel, Ulrich
Chen, Guanjie
Zhou, Jie
Wassertheil-Smoller, Sylvia
Neuhouser, Marian L.
Rampersaud, Evadnie
Psaty, Bruce
Kooperberg, Charles
Manson, Joann E.
Kuller, Lewis H.
Ochs-Balcom, Heather M.
Johnson, Karen C.
Sucheston, Lara
Ordovas, Jose M.
Palmer, Julie R.
Haiman, Christopher A.
McKnight, Barbara
Howard, Barbara V.
Becker, Diane M.
Bielak, Lawrence F.
Liu, Yongmei
Allison, Matthew A.
Grant, Struan F. A.
Burke, Gregory L.
Patel, Sanjay R.
Schreiner, Pamela J.
Borecki, Ingrid B.
Evans, Michele K.
Taylor, Herman
Sale, Michele M.
Howard, Virginia
Carlson, Christopher S.
Rotimi, Charles N.
Cushman, Mary
Harris, Tamara B.
Reiner, Alexander P.
Cupples, L. Adrienne
North, Kari E.
Fox, Caroline S.
CA Writing Grp
TI Genome-Wide Association of Body Fat Distribution in African Ancestry
Populations Suggests New Loci
SO PLOS GENETICS
LA English
DT Article
ID DISEASE RISK-FACTORS; WAIST-HIP RATIO; ENVIRONMENTAL-INFLUENCES;
ADIPOSE-TISSUE; MASS INDEX; US ADULTS; WOMEN; OBESITY; CIRCUMFERENCE;
INDIVIDUALS
AB Central obesity, measured by waist circumference (WC) or waist-hip ratio (WHR), is a marker of body fat distribution. Although obesity disproportionately affects minority populations, few studies have conducted genome-wide association study (GWAS) of fat distribution among those of predominantly African ancestry (AA). We performed GWAS of WC and WHR, adjusted and unadjusted for BMI, in up to 33,591 and 27,350 AA individuals, respectively. We identified loci associated with fat distribution in AA individuals using meta-analyses of GWA results for WC and WHR (stage 1). Overall, 25 SNPs with single genomic control (GC)-corrected p-values, 5.0610 26 were followed-up (stage 2) in AA with WC and with WHR. Additionally, we interrogated genomic regions of previously identified European ancestry (EA) WHR loci among AA. In joint analysis of association results including both Stage 1 and 2 cohorts, 2 SNPs demonstrated association, rs2075064 at LHX2, p= 2.24610 28 for WC-adjusted-for-BMI, and rs6931262 at RREB1, p= 2.48610 28 for WHR-adjusted-for-BMI. However, neither signal was genome-wide significant after double GC-correction (LHX2: p = 6.5610 28; RREB1: p = 5.7610 28). Six of fourteen previously reported loci for waist in EA populations were significant (p, 0.05 divided by the number of independent SNPs within the region) in AA studied here (TBX15-WARS2, GRB14, ADAMTS9, LY86, RSPO3, ITPR2-SSPN). Further, we observed associations with metabolic traits: rs13389219 at GRB14 associated with HDL-cholesterol, triglycerides, and fasting insulin, and rs13060013 at ADAMTS9 with HDL-cholesterol and fasting insulin. Finally, we observed nominal evidence for sexual dimorphism, with stronger results in AA women at the GRB14 locus (p for interaction = 0.02). In conclusion, we identified two suggestive loci associated with fat distribution in AA populations in addition to confirming 6 loci previously identified in populations of EA. These findings reinforce the concept that there are fat distribution loci that are independent of generalized adiposity.
C1 [Liu, Ching-Ti; Xue, Luting; Griffin, Paula J.; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Monda, Keri L.; Taylor, Kira C.; North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Taylor, Kira C.] Univ Louisville, Dept Epidemiol & Populat Hlth, Louisville, KY 40292 USA.
[Lange, Leslie; Ellis, Jaclyn C.] UNC Sch Med, Dept Genet, Chapel Hill, NC USA.
[Demerath, Ellen W.] Univ Minnesota, Minneapolis, MN USA.
[Palmas, Walter] Columbia Univ, Dept Med, New York, NY USA.
[Wojczynski, Mary K.; Borecki, Ingrid B.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA.
[Vitolins, Mara Z.] Wake Forest Univ Hlth Sci, Dept Epidemiol & Prevent, Winston Salem, NC USA.
[Liu, Simin] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA.
[Liu, Simin] Dept Med, Los Angeles, CA USA.
[Liu, Simin] Dept Obstet & Gynecol, Los Angeles, CA USA.
[Liu, Simin] Ctr Metab Dis Prevent, Los Angeles, CA USA.
[Papanicolaou, George J.] NHLBI, Div Cardiovasc Sci, Prevent & Populat Sci Program, Bethesda, MD 20892 USA.
[Irvin, Marguerite R.; Kabagambe, Edmond] UAB, Dept Epidemiol, Birmingham, MD USA.
[Nalls, Michael A.; Britton, Angela F.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Adeyemo, Adebowale; Shriner, Daniel; Chen, Guanjie; Zhou, Jie; Rotimi, Charles N.] NHGRI, Ctr Res Genom & Global Hlth, Bethesda, MD 20892 USA.
[Liu, Jiankang; Taylor, Herman] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA.
[Li, Guo] Univ Washington, Seattle, WA 98195 USA.
[Ruiz-Narvaez, Edward A.; Rosenberg, Lynn; Palmer, Julie R.] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA.
[Chen, Wei-Min; Chen, Fang; Mychaleckyj, Josyf; Nayak, Uma] Univ Virginia, Ctr Publ Hlth & Genom, Charlottesville, VA USA.
[Chen, Wei-Min; Chen, Fang; Mychaleckyj, Josyf; Nayak, Uma] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA.
[Henderson, Brian E.; Haiman, Christopher A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Millikan, Robert C.; Nyante, Sarah] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Millikan, Robert C.; Nyante, Sarah] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA.
[Ambrosone, Christine B.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA.
[Strom, Sara S.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[Guo, Xiuqing; Haritunians, Talin; Rotter, Jerome I.; Chen, Yii-Der Ida] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Andrews, Jeanette S.] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA.
[Sun, Yan V.; Zhao, Wei; Peyser, Patricia A.; Bielak, Lawrence F.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Mosley, Thomas H.] Univ Mississippi, Med Ctr, Dept Med, Div Geriatr, Jackson, MS 39216 USA.
[Yanek, Lisa R.; Becker, Diane M.] Johns Hopkins Sch Med, Dept Med, Baltimore, MD USA.
[Speliotes, Elizabeth K.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Smith, Megan] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Spruill, Ida] Med Univ S Carolina, Charleston, SC 29425 USA.
[Garvey, W. Timothy; Howard, Virginia] UAB Sch Publ Hlth, Dept Epidemiol, Birmingham, AL USA.
[Pettaway, Curtis] Univ Texas MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA.
[Bandera, Elisa V.] Canc Inst New Jersey, New Brunswick, NJ USA.
[Zonderman, Alan B.] NIA, Lab Personal & Cognit, NIH, NIH Biomed Ctr, Baltimore, MD 21224 USA.
[Rasmussen-Torvik, Laura J.] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA.
[Ding, Jingzhong] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med Geriatr, Winston Salem, NC USA.
[Lohman, Kurt] Wake Forest Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA.
[Kritchevsky, Stephen B.] Wake Forest Sch Med, Dept Internal Med Geriatr, Winston Salem, NC USA.
[Kardia, Sharon L. R.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Broeckel, Ulrich] Med Coll Wisconsin, Dept Pediat Med & Physiol, Milwaukee, WI 53226 USA.
[Wassertheil-Smoller, Sylvia] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
[Neuhouser, Marian L.; Carlson, Christopher S.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Rampersaud, Evadnie] Miami Inst Human Genom, Miami, FL USA.
[Rampersaud, Evadnie] Univ Miami, John T McDonald Dept Human Genet, Miami, FL USA.
[Psaty, Bruce] Grp Hlth Cooperat Puget Sound, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98121 USA.
[Psaty, Bruce] Grp Hlth Cooperat Puget Sound, Cardiovasc Hlth Res Unit, Dept Epidemiol, Seattle, WA 98121 USA.
[Psaty, Bruce] Grp Hlth Cooperat Puget Sound, Cardiovasc Hlth Res Unit, Dept Hlth Serv, Seattle, WA 98121 USA.
[Psaty, Bruce] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98121 USA.
[Kooperberg, Charles] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Manson, Joann E.] Harvard Univ, Brigham & Womens Hosp, Dept Med, Sch Med, Boston, MA 02115 USA.
[Kuller, Lewis H.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Ochs-Balcom, Heather M.] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA.
[Johnson, Karen C.] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA.
[Sucheston, Lara] SUNY Buffalo, Sch Publ Hlth & Hlth Profess, New York State Ctr Excellence Bioinformat & Life, Dept Biostat, Buffalo, NY 14260 USA.
[Ordovas, Jose M.] Tufts Univ, Boston, MA 02111 USA.
[McKnight, Barbara] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Howard, Barbara V.] MedStar Hlth Res Inst, Hyattsville, MD USA.
[Howard, Barbara V.] Georgetown Univ, Hyattsville, MD USA.
[Liu, Yongmei] Wake Forest Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA.
[Allison, Matthew A.] Univ Calif San Diego, Dept Prevent Med, La Jolla, CA 92093 USA.
[Grant, Struan F. A.] Childrens Hosp Philadelphia, Div Human Genet, Res Inst, Philadelphia, PA 19104 USA.
[Burke, Gregory L.] Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA.
[Patel, Sanjay R.] Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA.
[Schreiner, Pamela J.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Evans, Michele K.] NIA, Hlth Dispar Res Sect, Clin Res Branch, NIH,Biomed Ctr, Baltimore, MD 21224 USA.
[Sale, Michele M.] Univ Virginia, Ctr Publ Genom, Dept Biochem & Mol Genet, Charlottesville, VA USA.
[Sale, Michele M.] Univ Virginia, Dept Med, Charlottesville, VA USA.
[Cushman, Mary] Univ Vermont, Dept Med, Colchester, VT USA.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Reiner, Alexander P.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Cupples, L. Adrienne; Fox, Caroline S.] NHLBIs Framingham Heart Study, Framingham, MA USA.
[Fox, Caroline S.] NHLBIs Ctr Populat Studies, Framingham, MA USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA.
[Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA.
RP Liu, CT (reprint author), Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
EM knorth@email.unc.edu; Foxca@nhlbi.nih.gov
RI Liu, Simin/I-3689-2014; Bandera, Elisa/M-4169-2014;
OI Liu, Simin/0000-0003-2098-3844; Bandera, Elisa/0000-0002-8789-2755;
Rosenberg, Lynn/0000-0003-2760-2987; Ruiz-Narvaez,
Edward/0000-0002-0339-5824; Palmer, Julie/0000-0002-6534-335X; Cupples,
L. Adrienne/0000-0003-0273-7965; Patel, Sanjay/0000-0002-9142-5172;
Allison, Matthew/0000-0003-0777-8272; Zonderman, Alan
B/0000-0002-6523-4778; Kritchevsky, Stephen/0000-0003-3336-6781;
Adeyemo, Adebowale/0000-0002-3105-3231
FU Department of Defense Breast Cancer Research Program Era of Hope Scholar
Award; Norris Foundation; MEC (National Institutes of Health)
[R01-CA63464, R37CA54281]; WCHS (U. S. Army Medical Research and
Material Command (USAMRMC) [DAMD-17-01-0-0334]; National Institutes of
Health [R01CA100598]; Breast Cancer Research Foundation; CBCS (National
Institutes of Health Specialized Program of Research Excellence in
Breast Cancer) [P50-CA58223]; Center for Environmental Health and
Susceptibility National Institute of Environmental Health Sciences,
National Institutes of Health [P30-ES10126]; NIH [CA63464, CA54281,
CA1326792, CA148085, HG004726, R01-HL-087700, R01-HL-088215]; National
Cancer Institute [R01CA058920, R01CA098663]; NHLBI [N02-HL-6-4278,
N01HC- 65226]; National Center for Research Resources [UL1RR033176];
National Center for Advancing Translational Sciences, CTSI
[UL1TR000124]; National Institute of Diabetes and Digestive and Kidney
Diseases [DK063491]; NIDDK [R01-DK-8925601, R01-DK-075681]; [CA68578];
[ES007784]; [DAMD W81XWH-07-1-0645]; [CA140388]; [N01-HC-95159];
[N01-HC-95169]; [UL1-RR-024156]; [R01-HL-071051]; [R01-HL-071205];
[R01-HL-071250]; [R01-HL-071251]; [R01-HL-071252]; [R01-HL-071258];
[R01-HL-071259]; [UL1-RR-025005]
FX AABC and AAPC: AABC was supported by a Department of Defense Breast
Cancer Research Program Era of Hope Scholar Award to CAH and the Norris
Foundation. Each of the participating AABC studies was supported by the
following grants: MEC (National Institutes of Health grants R01-CA63464
and R37CA54281), WCHS (U. S. Army Medical Research and Material Command
(USAMRMC) grant DAMD-17-01-0-0334, the National Institutes of Health
grant R01CA100598, and the Breast Cancer Research Foundation), and CBCS
(National Institutes of Health Specialized Program of Research
Excellence in Breast Cancer, grant number P50-CA58223, and Center for
Environmental Health and Susceptibility National Institute of
Environmental Health Sciences, National Institutes of Health, grant
number P30-ES10126). The MEC prostate cancer study and the genotyping in
AAPC were supported by NIH grants CA63464, CA54281, CA1326792, CA148085
and HG004726. MDA was support by grants, CA68578, ES007784, DAMD
W81XWH-07-1-0645, and CA140388. The Black Women's Health Study (BWHS) is
a prospective study supported by the National Cancer Institute grants
R01CA058920 and R01CA098663. Candidate Gene Association Resource (CARe):
The following nine parent studies have contributed parent study data,
ancillary study data, and DNA samples through the Massachusetts
Institute of Technology Broad Institute (N01-HC-65226) to create this
genotype/ phenotype data base for wide dissemination to the biomedical
research community: Atherosclerosis Risk in Communities (ARIC):
University of North Carolina at Chapel Hill (N01-HC-55015), Baylor
Medical College (N01-HC-55016), University of Mississippi Medical Center
(N01-HC-55021), University of Minnesota (N01-HC-55019), Johns Hopkins
University (N01-HC-55020), University of Texas, Houston (N01-HC-55022),
University of North Carolina, Forsyth County (N01-HC-55018);
Cardiovascular Health Study (CHS): University of Washington
(N01-HC-85079), Wake Forest University (N01-HC-85080), Johns Hopkins
University (N01-HC-85081), University of Pittsburgh (N01-HC-85082),
University of California, Davis (N01-HC-85083), University of
California, Irvine (N01-HC-85084), New England Medical Center
(N01-HC-85085), University of Vermont (N01-HC-85086), Georgetown
University (N01HC- 35129), Johns Hopkins University (N01 HC-15103),
University of Wisconsin (N01-HC-75150), Geisinger Clinic (N01-HC-45133),
University of Washington (N01 HC-55222, U01 HL080295); Cleveland Family
Study (CFS): Case Western Reserve University (NIH HL 46380, M01RR00080);
Cooperative Study of Sickle Cell Disease (CSSCD): University of Illinois
(N01-HB-72982, N01-HB-97062), Howard University (N01-HB-72991,
N01-HB-97061), University of Miami (N01-HB-72992, N01-HB97064), Duke
University (N01-HB-72993), George Washington University (N01-HB-72994),
University of Tennessee (N01-HB-72995, N01-HB-97070), Yale University
(N01-HB-72996, N01-HB-97072), Children's Hospital-Philadelphia
(N01-HB-72997, N01-HB-97056), University of Chicago (N01-HB-72998,
N01-HB97053), Medical College of Georgia (N01-HB-73000, N01-HB-97060),
Washington University (N01-HB-73001, N01-HB-97071), Jewish Hospital and
Medical Center of Brooklyn (N01-HB-73002), Trustees of Health and
Hospitals of the City of Boston, Inc., (N01-HB-73003), Children's
Hospital-Oakland (N01-HB-73004, N01-H-97054), University of Mississippi
(N01-HB-73005), St. Luke's Hospital-New York (N01-HB-73006), Alta
Bates-Herrick Hospital (N01-HB-97051), Columbia University (N01HB-
97058), St.; Jude's Children's Research Hospital (N01-HB-97066),
Research Foundation, State University of New York-Albany (N01-HB-97068,
N01-HB-97069), New England Research Institute (N01-HB-97073), Interfaith
Medical Center-Brooklyn (N01-HB-97085); Coronary Artery Risk in Young
Adults (CARDIA): University of Alabama at Birmingham (N01-HC-48047),
University of Minnesota (N01-HC-48048), Northwestern University
(N01-HC-48049), Kaiser Foundation Research Institute (N01-HC48050),
University of Alabama at Birmingham (N01-HC-95095), Tufts-New England
Medical Center (N01-HC-45204), Wake Forest University (N01-HC-45205),
HarborUCLA Research and Education Institute (N01-HC-05187), University
of California, Irvine (N01-HC-45134, N01-HC-95100); Framingham Heart
Study (FHS): Boston University (N01-HC-25195, R01HL092577-01A1, RO1
HL076784, R01 AG028321); Jackson Heart Study (JHS): Jackson State
University (N01-HC-95170), University of Mississippi (N01-HC-95171),
Tougaloo College (N01-HC-95172); Multi-Ethnic Study of Atherosclerosis
(MESA): MESA, MESA Family, and the MESA SHARe project are conducted and
supported by the National Heart, Lung, and Blood Institute (NHLBI) in
collaboration with MESA investigators. Support for MESA is provided by
contracts N01-HC-95159 through N01-HC-95169 and UL1-RR-024156. Funding
for MESA Family is provided by grants R01-HL-071051, R01-HL-071205,
R01-HL-071250, R01-HL-071251, R01-HL-071252, R01-HL-071258,
R01-HL-071259, UL1-RR-025005. Funding for genotyping was provided by
NHLBI Contract N02-HL-6-4278 and N01HC- 65226. The authors thank the
other investigators, the staff, and the participants of the MESA study
for their valuable contributions. A full list of participating MESA
investigators and institutions can be found at http:// www. mesa-nhlbi.
org. Sleep Heart Health Study (SHHS): Johns Hopkins University (U01
HL064360), Case Western University (U01 HL063463), University of
California, Davis (U01 HL053916), University of Arizona (U01 HL053938),
University of Minnesota (relocating in 2006 to Univ Arizona) (U01
HL053934), University of Pittsburgh (U01 HL077813), Boston University
(U01 HL053941), MedStar Research Institute (U01 HL063429), Johns Hopkins
University (U01 HL053937). Family Heart Study: Cardiovascular Health
Study: Health Study: This CHS research was supported by NHLBI contracts
N01-HC-85239, N01HC- 85079 through N01-HC-85086; N01-HC-35129, N01
HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, HHSN268201200036C
and NHLBI grants HL080295, HL087652, HL085251, HL105756 with additional
contribution from NINDS. Additional support was provided through
AG-023629, AG-15928, AG-20098, and AG-027058 from the NIA. See also
http:// www. chs-nhlbi. org/ pi. htm. DNA handling and genotyping at
Cedars-Sinai Medical Center was supported in part by the National Center
for Research Resources, grant UL1RR033176, and is now at the National
Center for Advancing Translational Sciences, CTSI grant UL1TR000124; in
addition to the National Institute of Diabetes and Digestive and Kidney
Diseases grant DK063491 to the Southern California Diabetes
Endocrinology Research Center, and Cedars-Sinai Board of Governors'
Chair in Medical Genetics (JIR). The Family Heart Study (FamHS) was
supported by NIH grants R01-HL-087700 and R01-HL-088215 (Michael A.
Province, PI) from NHLBI; and R01-DK-8925601 and R01-DK-075681 (Ingrid
B. Borecki, PI) from NIDDK. The authors thank the staff and participants
of the FamHS for their important contributions.; GeneSTAR was supported
by the National Heart, Lung, and Blood Institute (NHLBI) through the
PROGENI (U01 HL72518) and STAMPEED (R01 HL087698-01) consortia as well
as grants HL58625-01A1, HL59684, and HL071025-01A1, and a grant from the
NIH/ National Institute of Nursing Research (NR0224103). Additional
support was provided by a grant from the NIH/ National Center for
Research Resources (M01-RR000052) to the Johns Hopkins General Clinical
Research Center. GENOA is supported by the National Institutes of
Health, grant numbers HL087660, HL100245 and MD002249. HANDLS: This
research was supported by the Intramural Research Program of the NIH,
National Institute on Aging and the National Center on Minority Health
and Health Disparities (project # Z01AG000513 and human subjects
protocol # 2009-149). Data analyses for the HANDLS study utilized the
high-performance computational capabilities of the Biowulf Linux cluster
at the National Institutes of Health, Bethesda, Md. (http:// biowulf.
nih. gov). Health ABC The Health Aging and Body Composition Study
(Health ABC) was funded by the National Institutes of Aging. This
research was supported by NIA contracts N01AG62101, N01AG62103, and
N01AG62106. The genome-wide association study was funded by NIA grant
1R01AG032098-01A1 to Wake Forest University Health Sciences and
genotyping services were provided by the Center for Inherited Disease
Research (CIDR). CIDR is fully funded through a federal contract from
the National Institutes of Health to The Johns Hopkins University,
contract number HHSN268200782096C. This research was supported in part
by the Intramural Research Program of the NIH, National Institute on
Aging. HUFS: The HUFS was supported by grants S06GM008016-320107 to CR
and S06GM008016-380111 to AA, both from the NIGMS/ MBRS/ SCORE Program.
Participant enrollment was carried out at the Howard University General
Clinical Research Center (GCRC), supported by grant number 2M01RR010284
from the National Center for Research Resources (NCRR), a component of
the National Institutes of Health (NIH). Additional support was provided
by the Coriell Institute for Medical Research. This research was
supported in part by the Intramural Research Program of the National
Human Genome Research Institute, National Institutes of Health, in the
Center for Research in Genomics and Global Health. The Center for
Research on Genomics and Global Health is supported by the National
Human Genome Research Institute, the National Institute of Diabetes and
Digestive and Kidney Diseases, the Center for Information Technology,
and the Office of the Director at the National Institutes of Health
(Z01HG200362). The authors would like to thank participants in the
Howard University Family Study (HUFS) and the HUFS field staff. The role
of the Howard University General Clinical Research Center (GCRC) in
participant enrollment is hereby acknowledged. HyperGEN Genetics of Left
Ventricular Hypertrophy, ancillary to the Family Blood Pressure Program,
http:// clinicaltrials. gov/ ct/ show/ NCT00005267. Funding sources
included National Heart, Lung, and Blood Institute grant R01 HL55673 and
cooperative agreements (U10) with the National Heart, Lung, and Blood
Institute: HL54471, HL54515 (UT); HL54472, HL54496 (MN); HL54473 (DCC);
HL54495 (AL); HL54509 (NC).; SIGNET The Sea Islands Genetics Network
(SIGNET) is supported by R01 DK084350 (M Sale), and consists of data
from the REasons for Geographic And Racial Differences in Stroke
(REGARDS) cohort, (U01 NS041588; G Howard), Project SuGAR (Sea Islands
Genetic African American Registry; W. M. Keck Foundation; WT Garvey),
the Systemic Lupus Erythmatosus in Gullah Health (SLEIGH) study (G
Gilkeson), and a South Carolina Center of Biomedical Research Excellence
(COBRE) for Oral Health Project (P20-RR-17696; JK Fernandes). WHI The
WHI program is funded by the National Heart, Lung, and Blood Institute,
National Institutes of Health, U. S. Department of Health and Human
Services through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9,
32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221. This
manuscript was prepared in collaboration with investigators of the WHI,
and has been reviewed and/ or approved by the Women's Health Initiative
(WHI). WHI investigators are listed at http:// www. whiscience. org/
publications/ WHI_ investigators_ shortlist. pdf. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 46
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U1 0
U2 13
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 AUG
PY 2013
VL 9
IS 8
AR e1003681
DI 10.1371/journal.pgen.1003681
PG 16
WC Genetics & Heredity
SC Genetics & Heredity
GA 210KB
UT WOS:000323830300032
PM 23966867
ER
PT J
AU West, SK
Bailey, R
Munoz, B
Edwards, T
Mkocha, H
Gaydos, C
Lietman, T
Porco, T
Mabey, D
Quinn, TC
AF West, Sheila K.
Bailey, Robin
Munoz, Beatriz
Edwards, Tansy
Mkocha, Harran
Gaydos, Charlotte
Lietman, Thomas
Porco, Travis
Mabey, David
Quinn, Thomas C.
TI A Randomized Trial of Two Coverage Targets for Mass Treatment with
Azithromycin for Trachoma
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID CHLAMYDIA-TRACHOMATIS; ANTIBIOTIC-TREATMENT; INFECTION; COMMUNITY;
TANZANIA; ROUNDS
AB Background: The World Health Organization recommends at least 3 annual antibiotic mass drug administrations (MDA) where the prevalence of trachoma is >10% in children ages 1-9 years, with coverage at least at 80%. However, the additional value of higher coverage targeted at children with multiple rounds is unknown.
Trial Design: 2x2 factorial community randomized, double blind, trial.
Trial methods: 32 communities with prevalence of trachoma >= 20% were randomized to: annual MDA aiming for coverage of children between 80%-90% (usual target) versus aiming for coverage>90% (enhanced target); and to: MDA for three years versus a rule of cessation of MDA early if the estimated prevalence of ocular C. trachomatis infection was less than 5%. The primary outcome was the community prevalence of infection with C. trachomatis at 36 months.
Results: Over the trial's course, no community met the MDA cessation rule, so all communities had the full 3 rounds of MDA. At 36 months, there was no significant difference in the prevalence of infection, 4.0 versus 5.4 (mean adjusted difference = 1.4%, 95% CI = -1.0% to 3.8%), nor in the prevalence of trachoma, 6.1 versus 9.0 (mean adjusted difference = 2.6%, 95% CI = -0.3% to 5.3%) comparing the usual target to the enhanced target group. There was no difference if analyzed using coverage as a continuous variable.
Conclusion: In communities that had pre-treatment prevalence of follicular trachoma of 20% or greater, there is no evidence that MDA can be stopped before 3 annual rounds, even with high coverage. Increasing coverage in children above 90% does not appear to confer additional benefit.
C1 [West, Sheila K.; Munoz, Beatriz] Johns Hopkins Univ, Dana Ctr Prevent Ophthalmol, Baltimore, MD 21218 USA.
[Bailey, Robin; Edwards, Tansy; Mabey, David] London Sch Hyg & Trop Med, London WC1, England.
[Mkocha, Harran] Kongwa Trachoma Project, Kongwa, Tanzania.
[Gaydos, Charlotte] Johns Hopkins Univ, Dept Infect Dis, Int Chlamydia Lab, Baltimore, MD USA.
[Lietman, Thomas; Porco, Travis] Univ Calif San Francisco, Proctor Fdn, San Francisco, CA 94143 USA.
[Quinn, Thomas C.] NIAID, Div Intramural Res, Bethesda, MD USA.
RP West, SK (reprint author), Johns Hopkins Univ, Dana Ctr Prevent Ophthalmol, Baltimore, MD 21218 USA.
EM shwest@jhmi.edu
OI Mabey, David/0000-0002-0031-8276
FU Bill and Melinda Gates Foundation; Division of Intramural Research,
National Institutes of Allergy and Infectious Disease, National
Institutes of Health
FX This study was funded by a grant from the Bill and Melinda Gates
Foundation, and received partial funding from the Division of Intramural
Research, National Institutes of Allergy and Infectious Disease,
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 17
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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 1935-2735
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD AUG
PY 2013
VL 7
IS 8
AR e2415
DI 10.1371/journal.pntd.0002415
PG 7
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA 211WE
UT WOS:000323941500061
PM 24009792
ER
PT J
AU Bahl, J
Krauss, S
Kuhnert, D
Fourment, M
Raven, G
Pryor, SP
Niles, LJ
Danner, A
Walker, D
Mendenhall, IH
Su, YCF
Dugan, VG
Halpin, RA
Stockwell, TB
Webby, RJ
Wentworth, DE
Drummond, AJ
Smith, GJD
Webster, RG
AF Bahl, Justin
Krauss, Scott
Kuehnert, Denise
Fourment, Mathieu
Raven, Garnet
Pryor, S. Paul
Niles, Lawrence J.
Danner, Angela
Walker, David
Mendenhall, Ian H.
Su, Yvonne C. F.
Dugan, Vivien G.
Halpin, Rebecca A.
Stockwell, Timothy B.
Webby, Richard J.
Wentworth, David E.
Drummond, Alexei J.
Smith, Gavin J. D.
Webster, Robert G.
TI Influenza A Virus Migration and Persistence in North American Wild Birds
SO PLOS PATHOGENS
LA English
DT Article
ID H5N1 OUTBREAKS; DYNAMICS; PATTERNS; AMPLIFICATION; SURVEILLANCE;
PREVALENCE; POULTRY; FLYWAY; ALASKA; SWINE
AB Wild birds have been implicated in the emergence of human and livestock influenza. The successful prediction of viral spread and disease emergence, as well as formulation of preparedness plans have been hampered by a critical lack of knowledge of viral movements between different host populations. The patterns of viral spread and subsequent risk posed by wild bird viruses therefore remain unpredictable. Here we analyze genomic data, including 287 newly sequenced avian influenza A virus (AIV) samples isolated over a 34-year period of continuous systematic surveillance of North American migratory birds. We use a Bayesian statistical framework to test hypotheses of viral migration, population structure and patterns of genetic reassortment. Our results reveal that despite the high prevalence of Charadriiformes infected in Delaware Bay this host population does not appear to significantly contribute to the North American AIV diversity sampled in Anseriformes. In contrast, influenza viruses sampled from Anseriformes in Alberta are representative of the AIV diversity circulating in North American Anseriformes. While AIV may be restricted to specific migratory flyways over short time frames, our large-scale analysis showed that the long-term persistence of AIV was independent of bird flyways with migration between populations throughout North America. Analysis of long-term surveillance data provides vital insights to develop appropriately informed predictive models critical for pandemic preparedness and livestock protection.
C1 [Bahl, Justin; Fourment, Mathieu; Mendenhall, Ian H.; Su, Yvonne C. F.; Smith, Gavin J. D.] Duke NUS Grad Med Sch, Program Emerging Infect Dis, Lab Virus Evolut, Singapore, Singapore.
[Bahl, Justin] Univ Texas Houston, Sch Publ Hlth, Ctr Infect Dis, Houston, TX USA.
[Krauss, Scott; Danner, Angela; Walker, David; Webby, Richard J.; Webster, Robert G.] St Jude Childrens Res Hosp, Dept Infect Dis, Memphis, TN 38105 USA.
[Kuehnert, Denise; Drummond, Alexei J.] Univ Auckland, Dept Comp Sci, Auckland 1, New Zealand.
[Kuehnert, Denise; Drummond, Alexei J.] Univ Auckland, Allan Wilson Ctr Mol Ecol & Evolut, Auckland 1, New Zealand.
[Raven, Garnet; Pryor, S. Paul] Canadian Wildlife Serv, Environm Canada, Edmonton, AB, Canada.
[Niles, Lawrence J.] Conserve Wildlife Fdn New Jersey, Bordentown, NJ USA.
[Dugan, Vivien G.; Halpin, Rebecca A.; Stockwell, Timothy B.; Wentworth, David E.] J Craig Venter Inst, Rockville, MD USA.
[Dugan, Vivien G.] NIAID, Div Microbiol & Infect Dis, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Smith, Gavin J. D.] Duke Univ, Duke Global Hlth Inst, Durham, NC USA.
RP Bahl, J (reprint author), Duke NUS Grad Med Sch, Program Emerging Infect Dis, Lab Virus Evolut, Singapore, Singapore.
EM gavin.smith@duke-nus.edu.sg; robert.webster@stjude.org
RI Drummond, Alexei/A-3209-2010; Bahl, Justin/A-4728-2011;
OI Drummond, Alexei/0000-0003-4454-2576; Bahl, Justin/0000-0001-7572-4300;
Fourment, Mathieu/0000-0001-8153-9822; Wentworth,
David/0000-0002-5190-980X; Smith, Gavin JD/0000-0001-5031-468X; Kuhnert,
Denise/0000-0002-5657-018X
FU National Institute of Allergy and Infectious Disease, National
Institutes of Health, Department of Health and Human Services
[HHSN266200700005C, HHSN272200900007]; Duke-NUS Signature Research
Program; Agency for Science, Technology and Research, Singapore;
Ministry of Health, Singapore
FX This study was supported by contracts HHSN266200700005C, and
HHSN272200900007 from the National Institute of Allergy and Infectious
Disease, National Institutes of Health, Department of Health and Human
Services. JB and GJDS are supported by the Duke-NUS Signature Research
Program funded by the Agency for Science, Technology and Research,
Singapore, and the Ministry of Health, Singapore. 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 39
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD AUG
PY 2013
VL 9
IS 8
AR e1003570
DI 10.1371/journal.ppat.1003570
PG 12
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 211EQ
UT WOS:000323888200060
PM 24009503
ER
PT J
AU Ellis, TC
Jain, S
Linowski, AK
Rike, K
Bestor, A
Rosa, PA
Halpern, M
Kurhanewicz, S
Jewett, MW
AF Ellis, Tisha Choudhury
Jain, Sunny
Linowski, Angelika K.
Rike, Kelli
Bestor, Aaron
Rosa, Patricia A.
Halpern, Micah
Kurhanewicz, Stephanie
Jewett, Mollie W.
TI In Vivo Expression Technology Identifies a Novel Virulence Factor
Critical for Borrelia burgdorferi Persistence in Mice
SO PLOS PATHOGENS
LA English
DT Article
ID LYME-DISEASE SPIROCHETE; VLSE ANTIGENIC VARIATION; LINEAR PLASMIDS 1P25;
SURFACE PROTEIN-C; GENE-EXPRESSION; MAMMALIAN HOST; BACTERIAL VIRULENCE;
INFECTIOUS CYCLE; TICK VECTOR; DISSEMINATION
AB Analysis of the transcriptome of Borrelia burgdorferi, the causative agent of Lyme disease, during infection has proven difficult due to the low spirochete loads in the mammalian tissues. To overcome this challenge, we have developed an In Vivo Expression Technology (IVET) system for identification of B. burgdorferi genes expressed during an active murine infection. Spirochetes lacking linear plasmid (lp) 25 are non-infectious yet highly transformable. Mouse infection can be restored to these spirochetes by expression of the essential lp25-encoded pncA gene alone. Therefore, this IVET-based approach selects for in vivo-expressed promoters that drive expression of pncA resulting in the recovery of infectious spirochetes lacking lp25 following a three week infection in mice. Screening of approximately 15,000 clones in mice identified 289 unique in vivo-expressed DNA fragments from across all 22 replicons of the B. burgdorferi B31 genome. The in vivo-expressed candidate genes putatively encode proteins in various functional categories including antigenicity, metabolism, motility, nutrient transport and unknown functions. Candidate gene bbk46 on essential virulence plasmid lp36 was found to be highly induced in vivo and to be RpoS-independent. Immunocompetent mice inoculated with spirochetes lacking bbk46 seroconverted but no spirochetes were recovered from mouse tissues three weeks post inoculation. However, the bbk46 gene was not required for B. burgdorferi infection of immunodeficient mice. Therefore, through an initial IVET screen in B. burgdorferi we have identified a novel in vivo-induced virulence factor critical for the ability of the spirochete to evade the humoral immune response and persistently infect mice.
C1 [Ellis, Tisha Choudhury; Jain, Sunny; Linowski, Angelika K.; Rike, Kelli; Halpern, Micah; Kurhanewicz, Stephanie; Jewett, Mollie W.] Univ Cent Florida, Coll Med, Burnett Sch Biomed Sci, Orlando, FL 32816 USA.
[Bestor, Aaron; Rosa, Patricia A.] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
RP Ellis, TC (reprint author), Univ Cent Florida, Coll Med, Burnett Sch Biomed Sci, Orlando, FL 32816 USA.
EM Mollie.Jewett@ucf.edu
FU National Institute of Allergy and Infectious Diseases of the National
Institutes of Health [K22AI081730, R01AI099094]; Intramural Research
Program, NIAID/NIH; National Research Fund for Tick-Borne Diseases; UCF
FX Research reported in this publication was supported by the National
Institute of Allergy and Infectious Diseases of the National Institutes
of Health under award numbers K22AI081730 (MWJ) and R01AI099094 (MWJ),
the Intramural Research Program, NIAID/NIH (PAR), the National Research
Fund for Tick-Borne Diseases 2012-2013 pilot grant (MWJ) and UCF startup
funds (MWJ). The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 83
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PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD AUG
PY 2013
VL 9
IS 8
AR e1003567
DI 10.1371/journal.ppat.1003567
PG 18
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 211EQ
UT WOS:000323888200057
PM 24009501
ER
PT J
AU Myeni, S
Child, R
Ng, TW
Kupko, JJ
Wehrly, TD
Porcella, SF
Knodler, LA
Celli, J
AF Myeni, Sebenzile
Child, Robert
Ng, Tony W.
Kupko, John J., III
Wehrly, Tara D.
Porcella, Stephen F.
Knodler, Leigh A.
Celli, Jean
TI Brucella Modulates Secretory Trafficking via Multiple Type IV Secretion
Effector Proteins
SO PLOS PATHOGENS
LA English
DT Article
ID NUCLEOTIDE-EXCHANGE FACTOR; ENDOPLASMIC-RETICULUM;
LEGIONELLA-PNEUMOPHILA; INTRACELLULAR REPLICATION;
YERSINIA-ENTEROCOLITICA; MEMBRANE COMPARTMENTS; ESCHERICHIA-COLI;
GOLGI-COMPLEX; LIVING CELLS; BREFELDIN-A
AB The intracellular pathogenic bacterium Brucella generates a replicative vacuole (rBCV) derived from the endoplasmic reticulum via subversion of the host cell secretory pathway. rBCV biogenesis requires the expression of the Type IV secretion system (T4SS) VirB, which is thought to translocate effector proteins that modulate membrane trafficking along the endocytic and secretory pathways. To date, only a few T4SS substrates have been identified, whose molecular functions remain unknown. Here, we used an in silico screen to identify putative T4SS effector candidate proteins using criteria such as limited homology in other bacterial genera, the presence of features similar to known VirB T4SS effectors, GC content and presence of eukaryotic-like motifs. Using beta-lactamase and CyaA adenylate cyclase reporter assays, we identified eleven proteins translocated into host cells by Brucella, five in a VirB T4SS-dependent manner, namely BAB1_0678 (BspA), BAB1_0712 (BspB), BAB1_0847 (BspC), BAB1_1671 (BspE) and BAB1_1948 (BspF). A subset of the translocated proteins targeted secretory pathway compartments when ectopically expressed in HeLa cells, and the VirB effectors BspA, BspB and BspF inhibited protein secretion. Brucella infection also impaired host protein secretion in a process requiring BspA, BspB and BspF. Single or combined deletions of bspA, bspB and bspF affected Brucella ability to replicate in macrophages and persist in the liver of infected mice. Taken together, these findings demonstrate that Brucella modulates secretory trafficking via multiple T4SS effector proteins that likely act coordinately to promote Brucella pathogenesis.
C1 [Myeni, Sebenzile; Child, Robert; Ng, Tony W.; Wehrly, Tara D.; Celli, Jean] Natl Inst Allergy & Infect Dis, Natl Inst Hlth, Rocky Mt Labs, Intracellular Parasites Lab, Hamilton, MT USA.
[Kupko, John J., III; Porcella, Stephen F.] Natl Inst Allergy & Infect Dis, Natl Inst Hlth, Rocky Mt Labs, Res Technol Sect,Genom Unit, Hamilton, MT USA.
[Knodler, Leigh A.] Washington State Univ, Coll Vet Med, Paul G Allen Sch Global Anim Hlth, Pullman, WA 99164 USA.
RP Myeni, S (reprint author), Natl Inst Allergy & Infect Dis, Natl Inst Hlth, Rocky Mt Labs, Intracellular Parasites Lab, Hamilton, MT USA.
EM jcelli@vetmed.wsu.edu
FU National Institutes of Health, National Institute of Allergy and
Infectious Diseases [AI000954-01]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Allergy and
Infectious Diseases, project #AI000954-01. 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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U2 14
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD AUG
PY 2013
VL 9
IS 8
AR e1003556
DI 10.1371/journal.ppat.1003556
PG 18
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 211EQ
UT WOS:000323888200046
PM 23950720
ER
PT J
AU Schowalter, RM
Buck, CB
AF Schowalter, Rachel M.
Buck, Christopher B.
TI The Merkel Cell Polyomavirus Minor Capsid Protein
SO PLOS PATHOGENS
LA English
DT Article
ID SIMIAN VIRUS-40; STRUCTURAL PROTEINS; LIFE-CYCLE; MESSENGER-RNAS;
T-ANTIGEN; IDENTIFICATION; INFECTION; VP2; SIMIAN-VIRUS-40; GENOME
AB The surface of polyomavirus virions is composed of pentameric knobs of the major capsid protein, VP1. In previously studied polyomavirus species, such as SV40, two interior capsid proteins, VP2 and VP3, emerge from the virion to play important roles during the infectious entry process. Translation of the VP3 protein initiates at a highly conserved Met-Ala-Leu motif within the VP2 open reading frame. Phylogenetic analyses indicate that Merkel cell polyomavirus ( MCV or MCPyV) is a member of a divergent clade of polyomaviruses that lack the conserved VP3 N-terminal motif. Consistent with this observation, we show that VP3 is not detectable in MCV-infected cells, VP3 is not found in native MCV virions, and mutation of possible alternative VP3-initiating methionine codons did not significantly affect MCV infectivity in culture. In contrast, VP2 knockout resulted in a > 100-fold decrease in native MCV infectivity, despite normal virion assembly, viral DNA packaging, and cell attachment. Although pseudovirus-based experiments confirmed that VP2 plays an essential role for infection of some cell lines, other cell lines were readily transduced by pseudovirions lacking VP2. In cell lines where VP2 was needed for efficient infectious entry, the presence of a conserved myristoyl modification on the N-terminus of VP2 was important for its function. The results show that a single minor capsid protein, VP2, facilitates a post-attachment stage of MCV infectious entry into some, but not all, cell types.
C1 [Schowalter, Rachel M.; Buck, Christopher B.] NCI, Natl Inst Hlth, Ctr Canc Res, Cellular Oncol Lab,Tumor Virus Mol Biol Sect, Bethesda, MD 20892 USA.
RP Schowalter, RM (reprint author), NCI, Natl Inst Hlth, Ctr Canc Res, Cellular Oncol Lab,Tumor Virus Mol Biol Sect, Bethesda, MD 20892 USA.
EM buckc@mail.nih.gov
OI Buck, Christopher/0000-0003-3165-8094
FU NIH; Center for Cancer Research, National Cancer Institute
FX This research was funded by the Intramural Research Program of the NIH,
with support from the Center for Cancer Research, National Cancer
Institute. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
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U2 15
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD AUG
PY 2013
VL 9
IS 8
AR e1003558
DI 10.1371/journal.ppat.1003558
PG 20
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 211EQ
UT WOS:000323888200048
PM 23990782
ER
PT J
AU Wu, F
Kirmaier, A
Goeken, R
Ourmanov, I
Hall, L
Morgan, JS
Matsuda, K
Buckler-White, A
Tomioka, K
Plishka, R
Whitted, S
Johnson, W
Hirsch, VM
AF Wu, Fan
Kirmaier, Andrea
Goeken, Robert
Ourmanov, Ilnour
Hall, Laura
Morgan, Jennifer S.
Matsuda, Kenta
Buckler-White, Alicia
Tomioka, Keiko
Plishka, Ronald
Whitted, Sonya
Johnson, Welkin
Hirsch, Vanessa M.
TI TRIM5 alpha Drives SIVsmm Evolution in Rhesus Macaques
SO PLOS PATHOGENS
LA English
DT Article
ID SIMIAN IMMUNODEFICIENCY VIRUS; TRIM5-ALPHA RESTRICTION FACTOR;
RETROVIRAL RESTRICTION; HIV-1 INFECTION; MONKEY TRIM5-ALPHA; PRIMATE
TRIM5-ALPHA; B30.2(SPRY) DOMAIN; CYCLOPHILIN-A; MNE VARIANT; GENE
AB The antagonistic interaction with host restriction proteins is a major driver of evolutionary change for viruses. We previously reported that polymorphisms of the TRIM5 alpha B30.2/SPRY domain impacted the level of SIVsmm viremia in rhesus macaques. Viremia in macaques homozygous for the non-restrictive TRIM5 alpha allele TRIM5(Q) was significantly higher than in macaques expressing two restrictive TRIM5alpha alleles TRIM5(TFP/TFP) or TRIM5(Cyp/TFP). Using this model, we observed that despite an early impact on viremia, SIVsmm overcame TRIM5 alpha restriction at later stages of infection and that increasing viremia was associated with specific amino acid substitutions in capsid. Two amino acid substitutions (P37S and R98S) in the capsid region were associated with escape from TRIM5(TFP) restriction and substitutions in the CypA binding-loop (GPLPA87-91) in capsid were associated with escape from TRIM5(Cyp). Introduction of these mutations into the original SIVsmE543 clone not only resulted in escape from TRIM5 alpha restriction in vitro but the P37S and R98S substitutions improved virus fitness in macaques with homozygous restrictive TRIMTFP alleles in vivo. Similar substitutions were observed in other SIVsmm strains following transmission and passage in macaques, collectively providing direct evidence that TRIM5 alpha exerts selective pressure on the cross-species transmission of SIV in primates.
C1 [Wu, Fan; Goeken, Robert; Ourmanov, Ilnour; Matsuda, Kenta; Buckler-White, Alicia; Tomioka, Keiko; Plishka, Ronald; Whitted, Sonya; Hirsch, Vanessa M.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Kirmaier, Andrea; Hall, Laura; Morgan, Jennifer S.; Johnson, Welkin] Boston Coll, Dept Biol, Chestnut Hill, MA 02167 USA.
RP Wu, F (reprint author), NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
EM vhirsch@niaid.nih.gov
OI Kirmaier, Andrea/0000-0001-7206-7640
FU NIAID; NIH [AI083118, AI095092]
FX This work was supported by the intramural program of NIAID, and NIH
awards AI083118 and AI095092 (WJ). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 79
TC 14
Z9 14
U1 0
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD AUG
PY 2013
VL 9
IS 8
AR e1003577
DI 10.1371/journal.ppat.1003577
PG 14
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 211EQ
UT WOS:000323888200066
PM 23990789
ER
PT J
AU Kozhich, OA
Hamilton, RS
Mallon, BS
AF Kozhich, O. A.
Hamilton, R. S.
Mallon, B. S.
TI Standardized Generation and Differentiation of Neural Precursor Cells
from Human Pluripotent Stem Cells
SO STEM CELL REVIEWS AND REPORTS
LA English
DT Article
DE Pluripotent stem cells; Differentiation; Neural precursor; Neurons
ID IN-VITRO; NEURONAL DIFFERENTIATION; EFFICIENT GENERATION;
DOPAMINERGIC-NEURONS; HUMAN ES; DERIVATION; CULTURE
AB Precise, robust and scalable directed differentiation of pluripotent stem cells is an important goal with respect to disease modeling or future therapies. Using the AggreWell (TM) 400 system we have standardized the differentiation of human embryonic and induced pluripotent stem cells to a neuronal fate using defined conditions. This allows reproducibility in replicate experiments and facilitates the direct comparison of cell lines. Since the starting point for EB formation is a single cell suspension, this protocol is suitable for standard and novel methods of pluripotent stem cell culture. Moreover, an intermediate population of neural precursor cells, which are routinely > 95% NCAM(pos) and Tra-1-60(neg) by FACS analysis, may be expanded and frozen prior to differentiation allowing a convenient starting point for downstream experiments.
C1 [Kozhich, O. A.] NINDS, Mol Biol Lab, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Hamilton, R. S.; Mallon, B. S.] NINDS, NIH Stem Cell Unit, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
RP Mallon, BS (reprint author), NINDS, NIH Stem Cell Unit, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
EM mallonb@mail.nih.gov
FU Intramural Research Program of the NIH, NINDS
FX We gratefully acknowledge Dr. Sergei Kuznetsov and Dr. Pamela Robey of
the National Institute for Dental and Craniofacial Research for
providing the bone marrow stromal cells from which the iPSC line was
derived. We would also like to thank Dr. Ron McKay and Dr. Josh
Chenoweth of the Lieber Institute for Brain Development for helpful
discussions. This research was supported by the Intramural Research
Program of the NIH, NINDS.
NR 31
TC 6
Z9 6
U1 3
U2 9
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 1550-8943
J9 STEM CELL REV REP
JI Stem Cell Rev. Rep.
PD AUG
PY 2013
VL 9
IS 4
BP 531
EP 536
DI 10.1007/s12015-012-9357-8
PG 6
WC Cell & Tissue Engineering; Cell Biology; Medicine, Research &
Experimental
SC Cell Biology; Research & Experimental Medicine
GA 202ZS
UT WOS:000323260500014
PM 22388559
ER
PT J
AU Caldwell, KL
Pan, Y
Mortensen, ME
Makhmudov, A
Merrill, L
Moye, J
AF Caldwell, Kathleen L.
Pan, Yi
Mortensen, Mary E.
Makhmudov, Amir
Merrill, Lori
Moye, John
TI Iodine Status in Pregnant Women in the National Children's Study and in
US Women (15-44 Years), National Health and Nutrition Examination Survey
2005-2010
SO THYROID
LA English
DT Article
ID UNITED-STATES; URINARY IODINE; MILK; AGE
AB Background: This report presents iodine data from National Health and Nutrition Examination Survey (NHANES) and from a sample of pregnant women in the National Children's Study (NCS) Vanguard Study.
Methods: Urinary iodine (UI) was measured in a one third subsample of NHANES 2005-2006 and 2009-2010 participants and in all 2007-2008 participants age 6 years and older. These measurements are representative of the general U.S. population. UI was also measured in a convenience sample of 501 pregnant women enrolled in the NCS initial Vanguard Study from seven study sites across the United States.
Results: NHANES median UI concentration in 2009-2010 (144 mu g/L) was significantly lower than in 2007-2008 (164 mu g/L). Non-Hispanic blacks had the lowest UI concentrations (131 mu g/L) compared with non-Hispanic whites or Hispanics (147 and 148 mu g/L, respectively). The median for all pregnant women in NHANES 2005-2010 was less than adequate (129 mu g/L), while third trimester women had UI concentrations that were adequate (median UI 172 mu g/L). Third trimester women participating in the NCS similarly had an adequate level of iodine intake, with a median UI concentration of 167 mu g/L. Furthermore, NCS median UI concentrations varied by geographic location.
Conclusions: Dairy, but not salt, seafood, or grain consumption, was significantly positively associated with median UI concentration in women of childbearing age. Pregnant women in their third trimester in the NHANES 2005-2010 had adequate median UI concentrations, but pregnant women in NHANES who were in their first or second trimesters had median UI concentrations that were less than adequate. Non-Hispanic black pregnant women from both the NHANES 2005-20010 and the NCS consistently had lower UI median concentrations than non-Hispanic whites or Hispanics.
C1 [Caldwell, Kathleen L.; Pan, Yi; Mortensen, Mary E.; Makhmudov, Amir] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Div Sci Lab, Atlanta, GA 30341 USA.
[Merrill, Lori] WESTAT Corp, Rockville, MD 20850 USA.
[Moye, John] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Natl Childrens Study Program Off, Bethesda, MD USA.
RP Caldwell, KL (reprint author), Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Div Sci Lab, 4770 Buford Highway NE,Mail Stop F-18, Atlanta, GA 30341 USA.
EM klc7@cdc.gov
OI moye, john/0000-0001-9976-8586
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD); Office of the Director of the National Institutes
of Health; NICHD [HHSN275200503414C, HHSN275200503411C,
HHSN275200603416C, HHSN275200503415C, HHSN275200503413C,
HHSN275200503410C, HHSN275200503396C]; National Center for Environmental
Health, Centers for Disease Control and Prevention
FX This 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 by NICHD Contracts HHSN275200503414C,
HHSN275200503411C, HHSN275200603416C, HHSN275200503415C,
HHSN275200503413C, HHSN275200503410C, and HHSN275200503396C. The
manuscript was developed by a Writing Team identified by the National
Children's Study Publications Committee for the purpose of timely
sharing of centrally collected NCS data. In addition, funding for the
biospecimen analyses was provided by the National Center for
Environmental Health, Centers for Disease Control and Prevention. The
findings and conclusions in this report are those of the authors and do
not necessarily represent the views of the Centers for Disease Control
and Prevention, the National Children's Study or the National Institutes
of Health, or the U.S. Department of Health and Human Services.
NR 23
TC 44
Z9 45
U1 1
U2 6
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1050-7256
J9 THYROID
JI Thyroid
PD AUG
PY 2013
VL 23
IS 8
BP 927
EP 937
DI 10.1089/thy.2013.0012
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 203RK
UT WOS:000323310500004
PM 23488982
ER
PT J
AU Aschebrook-Kilfoy, B
Grogan, RH
Ward, MH
Kaplan, E
Devesa, SS
AF Aschebrook-Kilfoy, Briseis
Grogan, Raymon H.
Ward, Mary H.
Kaplan, Edwin
Devesa, Susan S.
TI Follicular Thyroid Cancer Incidence Patterns in the United States,
1980-2009
SO THYROID
LA English
DT Article
ID PAPILLARY; TRENDS; NUTRITION; COHORT
AB Background: The increases in thyroid cancer overall and in the predominant papillary type have been well documented, but trends for follicular thyroid cancer, a less common but more aggressive variant, have not been as well characterized. In this study, we determined the incidence patterns for follicular thyroid cancer and compared trends between the follicular and papillary thyroid cancers in the United States.
Methods: We used the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program to examine incidence in the United States during 1980-2009, stratified by demographic and tumor characteristics. Incidence rates (IR) were calculated, relative risks were expressed as incidence rate ratios (IRR), and temporal trends were expressed as percentage changes and plotted.
Results: Overall we observed a modest increase in age-adjusted follicular thyroid cancer rates among women (31.89%) and men (35.88%). Rates increased most dramatically for regional stage tumors compared to localized tumors in women, whereas the rates for all tumor sizes rose. These findings reveal increases in more aggressive tumors in women in addition to small and localized tumors. The trends for males were different from those among females. Among males, the largest increase was observed for regional and smaller size tumors. The papillary-to-follicular IRR overall was 7.07 [95% confidence interval 6.91-7.24], which varied from 7.37 among Whites to 3.86 among Blacks (SEER race/ethnicity categories), and increased significantly from 3.98 during 1980-1984 to 9.88 during 2005-2009.
Conclusion: The different trends for follicular and papillary types of thyroid cancer illustrate that thyroid cancer is a heterogeneous disease. Our results do not support the hypothesis that increasing thyroid cancer rates are largely due to improvements in detection, and suggest the importance of evaluating thyroid cancer types separately in future studies.
C1 [Aschebrook-Kilfoy, Briseis] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA.
[Grogan, Raymon H.; Kaplan, Edwin] Univ Chicago, Endocrine Surg Res Program, Dept Surg, Sect Endocrine Surg,Pritzker Sch Med, Chicago, IL 60637 USA.
[Ward, Mary H.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept HHS, Bethesda, MD 20892 USA.
[Devesa, Susan S.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,Dept HHS, Bethesda, MD 20892 USA.
RP Aschebrook-Kilfoy, B (reprint author), Univ Chicago, Dept Hlth Studies, 5841 S Maryland Ave,N101B, Chicago, IL 60637 USA.
EM brisa@uchicago.edu
FU University of Chicago Comprehensive Cancer Center; Intramural Research
Program of the National Cancer Institute (NCI)
FX This research was supported in part by the University of Chicago
Comprehensive Cancer Center. This research was also supported in part by
the Intramural Research Program of the National Cancer Institute (NCI).
NR 27
TC 23
Z9 24
U1 1
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 AUG
PY 2013
VL 23
IS 8
BP 1015
EP 1021
DI 10.1089/thy.2012.0356
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 203RK
UT WOS:000323310500016
PM 23360496
ER
PT J
AU Ke, L
Graubard, BI
Albanes, D
Fraser, DR
Weinstein, SJ
Virtamo, J
Brock, KE
AF Ke, Liang
Graubard, Barry I.
Albanes, Demetrius
Fraser, David R.
Weinstein, Stephanie J.
Virtamo, Jarmo
Brock, Kaye E.
TI Hypertension, Pulse, and Other Cardiovascular Risk Factors and Vitamin D
Status in Finnish Men
SO AMERICAN JOURNAL OF HYPERTENSION
LA English
DT Article
DE blood pressure; coronary heart disease; diabetes; hypertension,
pulse/heart rate; vitamin D status; 25(OH)D
ID 25-HYDROXYVITAMIN D LEVELS; INCIDENT HYPERTENSION; BLOOD-PRESSURE;
WOMEN; SUPPLEMENTATION; OUTCOMES
AB BACKGROUND
Debate exists about the relationship between hypovitaminosis D and cardiovascular (CVD) risk.
METHODS
This study investigated baseline (n = 2,271) 25-hydroxyvitamin D (25(OH)D) and baseline and 4 year (n = 1,957) CVD risk in a cohort of Finnish middle-aged male smokers.
RESULTS
The prevalences of measured hypertension, high pulse rate, diabetes, and coronary heart disease were 63%, 16%, 5%, and 10% at baseline and were 64%, 20%, 6%, and 16% at 4 years after baseline. The mean 25(OH) D was 41 +/- 18 nmol/L. At baseline, systolic blood pressure (beta = -0.048; P = 0.02), and pulse rate (beta = -0.043; P = 0.04) were both associated with lower 25(OH)D levels but not coronary heart disease or diabetes prevalence. On remeasuring CVD risk 4 years after baseline, the only significant association with baseline 25(OH)D levels was high pulse rate (beta = -0.077; P = 0.001). In addition, a higher 25(OH) D level at baseline was associated with a change in pulse rate (beta = -0.055; P = 0.01). These trends for hypertension (baseline) and high pulse rate (baseline and 4 years after baseline) were also seen on adjusted categorical analysis (P-trend < 0.05).
CONCLUSIONS
Vitamin D deficiency at baseline was associated with hypertension in Finnish male smokers, but not after 4 years. These results are consistent with recent findings in other large cohort studies with measured blood pressure. Change in pulse rate over time continued to be significantly associated with lower 25(OH)D baseline levels; this new finding should be investigated further.
C1 [Ke, Liang; Brock, Kaye E.] Univ Sydney, Fac Hlth Sci, Sydney, NSW 2006, Australia.
[Graubard, Barry I.; Albanes, Demetrius; Weinstein, Stephanie J.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Fraser, David R.] Univ Sydney, Fac Vet Sci, Sydney, NSW 2006, Australia.
[Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
RP Brock, KE (reprint author), Univ Sydney, Fac Hlth Sci, Sydney, NSW 2006, Australia.
EM kaye.brock@sydney.edu.au
RI Albanes, Demetrius/B-9749-2015
FU US Public Health Service from the National Cancer Institute, Department
of Health and Human Services [N01-CN-45165, N01-RC-45035, N01-RC-37004,
HHSN261201000006C]; Intramural Research Program of the National Cancer
Institute
FX We acknowledge and thank the vitamin D collaborators in whose
laboratories the analyses were undertaken: R. Vieth: Departments of
Nutritional Sciences, and Laboratory Medicine and Pathobiology,
University of Toronto, Toronto, Canada; B. W. Hollis: Department of
Pediatrics, Division of Pediatric Nutritional Sciences, Medical
University of South Carolina, Charleston, South Carolina; R. Horst:
Heartland Assays Ames, Iowa. The ATBC Study was supported in part by US
Public Health Service (contract numbers N01-CN-45165, N01-RC-45035,
N01-RC-37004, and HHSN261201000006C) from the National Cancer Institute,
Department of Health and Human Services, and the Intramural Research
Program of the National Cancer Institute.
NR 20
TC 8
Z9 10
U1 0
U2 10
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0895-7061
J9 AM J HYPERTENS
JI Am. J. Hypertens.
PD AUG
PY 2013
VL 26
IS 8
BP 951
EP 956
DI 10.1093/ajh/hpt051
PG 6
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 182CO
UT WOS:000321718300002
PM 23598420
ER
PT J
AU Miloslavsky, EM
Specks, U
Merkel, PA
Seo, P
Spiera, R
Langford, CA
Hoffman, GS
Kallenberg, CGM
St Clair, EW
Tchao, NK
Viviano, L
Ding, L
Sejismundo, LP
Mieras, K
Ikle, D
Jepson, B
Mueller, M
Brunetta, P
Allen, NB
Fervenza, FC
Geetha, D
Keogh, K
Kissin, EY
Monach, PA
Peikert, T
Stegeman, C
Ytterberg, SR
Stone, JH
AF Miloslavsky, E. M.
Specks, U.
Merkel, P. A.
Seo, P.
Spiera, R.
Langford, C. A.
Hoffman, G. S.
Kallenberg, C. G. M.
St Clair, E. W.
Tchao, N. K.
Viviano, L.
Ding, L.
Sejismundo, L. P.
Mieras, K.
Ikle, D.
Jepson, B.
Mueller, M.
Brunetta, P.
Allen, N. B.
Fervenza, F. C.
Geetha, D.
Keogh, K.
Kissin, E. Y.
Monach, P. A.
Peikert, T.
Stegeman, C.
Ytterberg, S. R.
Stone, J. H.
CA Rituximab ANCA-Associated
TI Clinical Outcomes of Remission Induction Therapy for Severe
Antineutrophil Cytoplasmic Antibody-Associated Vasculitis
SO ARTHRITIS AND RHEUMATISM
LA English
DT Article
ID ANCA-ASSOCIATED VASCULITIS; DAILY ORAL CYCLOPHOSPHAMIDE;
RANDOMIZED-TRIAL; FOLLOW-UP; RITUXIMAB; MAINTENANCE; AUTOANTIBODIES;
GRANULOMATOSIS; AZATHIOPRINE; METHOTREXATE
AB Objective. To evaluate the reasons that complete remission is not achieved or maintained with original treatment in some patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) treated with rituximab (RTX) or with cyclophosphamide/azathioprine (CYC/AZA).
Methods. The Rituximab in AAV trial was a randomized, double-blind, placebo-controlled trial comparing the rate of remission induction among patients treated with RTX (n = 99) and patients treated with CYC followed by AZA (n = 98). Glucocorticoids were tapered over a period of 5 months. The primary outcome measure was lack of disease activity without glucocorticoid treatment at 6 months. To determine the most important reason for failure to achieve the primary outcome, 7 hierarchical categories of reasons were defined retrospectively (uncontrolled disease, adverse event leading to therapy discontinuation, severe flare, limited flare, Birmingham Vasculitis Activity Score for Wegener's Granulomatosis >0, prednisone treatment at any dosage, and other).
Results. Although remission (lack of disease activity) was achieved in 170 of the 197 patients (86%) in the first 6 months, the primary outcome measure was not achieved in 42%. There were 3 deaths. Twenty-four percent of the patients failed to achieve the primary end point due to active disease: 10 (5%) experienced uncontrolled disease in the first month and 37 (19%) experienced flares after initial improvement. In the majority of such patients, treatment with blinded crossover or according to best medical judgment led to disease control. Ninety-one percent of patients who had uncontrolled disease or experienced a severe flare had proteinase 3 (PR3)-ANCA. When patients with uncontrolled disease were excluded from analysis, those who were PR3-ANCA positive were found to experience fewer flares when treated with RTX compared to CYC/AZA (8 of 59 [14%] versus 20 of 62 [32%]; P = 0.02). Neither ANCA titers nor B cell counts predicted disease flare.
Conclusion. Current treatment regimens are largely successful in controlling AAV, but in approximately one-fourth of patients, active disease persists or recurs in the first 6 months despite treatment. PR3- ANCA positivity is a risk factor for recurrence or persistence of severe disease. ANCA titers and B cell detectability are poor predictors of both disease relapse and disease quiescence in the first 6 months.
C1 [Miloslavsky, E. M.; Stone, J. H.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Specks, U.; Mieras, K.; Fervenza, F. C.; Keogh, K.; Peikert, T.; Ytterberg, S. R.] Mayo Clin, Rochester, MN USA.
[Merkel, P. A.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Seo, P.; Sejismundo, L. P.; Geetha, D.] Johns Hopkins Univ, Baltimore, MD USA.
[Spiera, R.] Hosp Special Surg, New York, NY 10021 USA.
[Langford, C. A.; Hoffman, G. S.] Cleveland Clin, Cleveland, OH 44106 USA.
[Kallenberg, C. G. M.; Stegeman, C.] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands.
[Kallenberg, C. G. M.; Stegeman, C.] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands.
[St Clair, E. W.; Allen, N. B.] Duke Univ, Med Ctr, Durham, NC USA.
[Tchao, N. K.] Immune Tolerance Network, San Francisco, CA USA.
[Viviano, L.; Ding, L.] NIAID, NIH, Bethesda, MD 20892 USA.
[Ikle, D.; Jepson, B.] Rho, Chapel Hill, NC USA.
[Mueller, M.] US FDA, Silver Spring, MD USA.
[Brunetta, P.] Genentech Inc, San Francisco, CA 94080 USA.
[Kissin, E. Y.; Monach, P. A.] Boston Univ, Sch Med, Boston, MA 02118 USA.
RP Stone, JH (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, Yawkey 2C,55 Fruit St, Boston, MA 02114 USA.
EM jhstone@partners.org
FU Immune Tolerance Network (NIH), an international clinical research
consortium headquartered at the University of California San Francisco
[N01-AI-15416, ITN021AI]; NIH (National Institute of Allergy and
Infectious Diseases) [N01-AI-15416, ITN021AI]; Juvenile Diabetes
Research Foundation; Genentech; Biogen Idec; NIH (Mayo Clinic: National
Center for Research Resources Clinical and Translational Science)
[RR-024150-01]; NIH (Johns Hopkins University: National Center for
Research Resources Clinical and Translational Science) [RR-025005,
K23-AR-052820, K24-AR-049185, RR-025771, M01-RR-00533, K24-AR-02224];
Arthritis Foundation
FX The Rituximab in ANCA-Associated Vasculitis (RAVE) trial was performed
with the support of the Immune Tolerance Network (NIH contract
N01-AI-15416, protocol number ITN021AI), an international clinical
research consortium headquartered at the University of California San
Francisco and supported by the NIH (National Institute of Allergy and
Infectious Diseases contract N01-AI-15416, protocol number ITN021AI) and
the Juvenile Diabetes Research Foundation. Genentech and Biogen Idec
provided the study medications and partial funding for the RAVE trial.
At the Mayo Clinic, Johns Hopkins University, and Boston University
School of Medicine, the RAVE trial was supported by the NIH (Mayo
Clinic: National Center for Research Resources Clinical and
Translational Science award RR-024150-01; Johns Hopkins University:
National Center for Research Resources Clinical and Translational
Science grant RR-025005 and career development awards K23-AR-052820 to
Dr. Seo and K24-AR-049185 to Dr. Stone; Boston University: National
Center for Research Resources Clinical and Translational Science award
RR-025771, grant M01-RR-00533, and career development award K24-AR-02224
to Dr. Merkel). Dr. Miloslavsky's work was supported by Genentech
(Clinical Immunology Fellowship). Dr. Monach's work was supported by the
Arthritis Foundation (Arthritis Investigator Award).
NR 21
TC 37
Z9 39
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD AUG
PY 2013
VL 65
IS 9
BP 2441
EP 2449
DI 10.1002/art.38044
PG 9
WC Rheumatology
SC Rheumatology
GA 205YR
UT WOS:000323481400027
PM 23754238
ER
PT J
AU Hannan, MT
Menz, HB
Jordan, JM
Cupples, LA
Cheng, CH
Hsu, YH
AF Hannan, Marian T.
Menz, Hylton B.
Jordan, Joanne M.
Cupples, L. Adrienne
Cheng, Chia-Ho
Hsu, Yi-Hsiang
TI High Heritability of Hallux Valgus and Lesser Toe Deformities in Adult
Men and Women
SO ARTHRITIS CARE & RESEARCH
LA English
DT Article
ID FOOT PROBLEMS; OLDER-PEOPLE; MANCHESTER SCALE; POPULATION; PREVALENCE;
PAIN; VALIDATION; ETIOLOGY; SAMPLE; TWIN
AB Objective. To estimate the heritability of 3 common disorders affecting the forefoot, i.e., hallux valgus, lesser toe deformities, and plantar forefoot soft tissue atrophy, in white adult men and women.
Methods. Between 2002 and 2008, a trained examiner used a validated foot examination to document the presence of hallux valgus, lesser toe deformities, and plantar soft tissue atrophy in 2,446 adults from the Framingham Foot Study. Among these, 1,370 participants with an available pedigree structure were included. Heritability was estimated using pedigree structures by the Sequential Oligogenic Linkage Analysis Routines package. Results were adjusted for age, sex, and body mass index.
Results. The mean age of the participants was 66 years (range 39-99 years) and 57% were women. The prevalence of hallux valgus, lesser toe deformities, and plantar soft tissue atrophy was 31%, 29.6%, and 28.4%, respectively. Significant heritability was found for hallux valgus (range 0.29-0.89, depending on age and sex) and lesser toe deformity (range 0.49-0.90, depending on age and sex). The heritability for lesser toe deformity in men and women ages >70 years was 0.65 (P = 9 x 10(-7)). Significant heritability was found for plantar soft tissue atrophy in men and women ages >70 years (H-2 = 0.37, P = 3.8 x 10(-3)).
Conclusion. To our knowledge, these are the first findings of heritability of foot disorders in humans, and they confirm the widely-held view that hallux valgus and lesser toe deformities are highly heritable in white men and women of European descent, underscoring the importance of future work to identify genetic determinants of the underlying genetic susceptibility to these common foot disorders.
C1 [Hannan, Marian T.; Hsu, Yi-Hsiang] Harvard Univ, Sch Med, Hebrew SeniorLife, Boston, MA USA.
[Hannan, Marian T.; Hsu, Yi-Hsiang] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Menz, Hylton B.] La Trobe Univ, Melbourne, Vic, Australia.
[Jordan, Joanne M.] Univ N Carolina, Chapel Hill, NC USA.
[Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Boston, MA USA.
[Cupples, L. Adrienne] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Cheng, Chia-Ho] Hebrew SeniorLife, Boston, MA USA.
RP Hannan, MT (reprint author), HSL, Inst Aging Res, 1200 Ctr St, Boston, MA 02131 USA.
EM hannan@hsl.harvard.edu
RI Menz, Hylton/B-4508-2013;
OI Menz, Hylton/0000-0002-2045-3846; Hannan, Marian/0000-0002-9586-6928
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases
[AR060492, AR047853]; National Heart, Lung, and Blood Institute
[N01-HC-25195]; National Health and Medical Research Council [433049];
Australian-American Fulbright Commission
FX Supported by the National Institute of Arthritis and Musculoskeletal and
Skin Diseases (grants AR060492 and AR047853) and the National Heart,
Lung, and Blood Institute's Framingham Heart Study (contract
N01-HC-25195). Dr. Menz is a National Health and Medical Research
Council fellow (Clinical Career Development Award 433049) and was
supported by an Australian-American Fulbright Commission Senior
Scholarship at the time this work was undertaken.
NR 44
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Z9 10
U1 1
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2151-464X
J9 ARTHRIT CARE RES
JI Arthritis Care Res.
PD AUG
PY 2013
VL 65
IS 9
BP 1515
EP 1521
DI 10.1002/acr.22040
PG 7
WC Rheumatology
SC Rheumatology
GA 205YJ
UT WOS:000323480600014
PM 23696165
ER
PT J
AU Ahn, SG
Dong, SM
Oshima, A
Kim, WH
Lee, HM
Lee, SA
Kwon, SH
Lee, JH
Lee, JM
Jeong, J
Lee, HD
Green, JE
AF Ahn, Sung Gwe
Dong, Seung Myung
Oshima, Akira
Kim, Woo Ho
Lee, Hak Min
Lee, Seung Ah
Kwon, Seung-hyun
Lee, Ji-hae
Lee, Jae Myun
Jeong, Joon
Lee, Hy-De
Green, Jeffrey E.
TI LOXL2 expression is associated with invasiveness and negatively
influences survival in breast cancer patients
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Breast cancer; LOXL2; Invasiveness; Triple negative
ID HUMAN LYSYL OXIDASE; TUMOR PROGRESSION; GENE; PROTEIN;
LYSYL-OXIDASE-LIKE-2; METASTASIS; STATISTICS; CARCINOMAS
AB Lysyl oxidase-like 2 (LOXL2) is associated with invasiveness and metastasis in breast cancer. We analyzed the prognostic impact of LOXL2 for breast cancer patients and investigated the role of LOXL2 in breast cancer cell lines. Immunohistochemical study of LOXL2 expression was done in samples from 309 patients. Survival analysis was performed using log-rank test and Cox regression hazard model. After identification of LOXL2 expression in breast cancer cell lines, we performed matrigel invasion and wound-healing assays with LOXL2-silenced cell lines. In the human study, LOXL2 was expressed in 16.2 % of patients. Comparing the LOXL2-positive versus negative groups, there was a significantly higher proportion of estrogen receptor-negative patients (54.0 vs. 37.0 %, respectively; p = 0.029) and triple-negative patients (34.0 vs. 18.0 %; p = 0.022) in the positive group. In multivariate analysis for overall survival and metastasis-free survival, positive LOXL2 was demonstrated as a poor prognostic factor (HR 2.27 and 2.10, respectively). In vitro study indicated that LOXL2 silencing induces a mesenchymal-epithelial transition-like process in basal cell lines (MDA-MB-231 and BT549) associated with decreased invasive and migratory properties. These clinical and preclinical data confirm that higher LOXL2 expression is associated with invasiveness of basal-like breast cancer cells and lower survival of breast cancer patients. Our results suggest the clinical value of LOXL2 as a therapeutic target in breast cancer.
C1 [Ahn, Sung Gwe; Lee, Hak Min; Jeong, Joon; Lee, Hy-De] Yonsei Univ, Coll Med, Gangnam Severance Hosp, Dept Surg, Seoul, South Korea.
[Dong, Seung Myung; Lee, Ji-hae] Natl Canc Ctr, Res Inst & Hosp, Goyang, Gyeonggi, South Korea.
[Oshima, Akira] Cha Univ, Cha Res Inst, Seoul, South Korea.
[Kim, Woo Ho] Seoul Natl Univ, Coll Med, Dept Pathol, Seoul 151, South Korea.
[Lee, Seung Ah] Eulji Univ, Coll Med, Dept Surg, Seoul, South Korea.
[Kwon, Seung-hyun; Lee, Jae Myun] Yonsei Univ, Coll Med, Dept Microbiol, Seoul, South Korea.
[Lee, Jae Myun] Yonsei Univ, Coll Med, Dept Microbiol, Brain Korea Project Med Sci 21, Seoul 120752, South Korea.
[Green, Jeffrey E.] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA.
RP Jeong, J (reprint author), Yonsei Univ, Coll Med, Gangnam Severance Hosp, Dept Surg, 712 Eonjuro, Seoul, South Korea.
EM jaemyun@yuhs.ac; gsjjoon@yuhs.ac
RI rchnds, rchnds/D-7595-2016;
OI Jeong, Joon/0000-0003-0397-0005
FU National Research Foundation of Korea (NRF); Korea government (MSIP)
[2007-0056092]; National Cancer Center [1110490]
FX This work was supported by the National Research Foundation of Korea
(NRF) grant funded by the Korea government (MSIP) (No. 2007-0056092),
and a research grant from National Cancer Center (1110490). Preparation
of the final manuscript was done with the assistance of BioScience
Writers LLC (Houston, TX). The authors acknowledge Dr. Janine T Erler
for advice on studying LOXL2-siRNA. The authors thank Mr. Dong-Su Jang,
Research Assistant, Department of Anatomy, Yonsei University College of
Medicine, Seoul, Korea, for his help with the figures.
NR 32
TC 21
Z9 21
U1 0
U2 10
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD AUG
PY 2013
VL 141
IS 1
BP 89
EP 99
DI 10.1007/s10549-013-2662-3
PG 11
WC Oncology
SC Oncology
GA 209DS
UT WOS:000323735000009
PM 23933800
ER
PT J
AU Sun, T
Qiao, HF
Pan, PY
Chen, YM
Sheng, ZH
AF Sun, Tao
Qiao, Haifa
Pan, Ping-Yue
Chen, Yanmin
Sheng, Zu-Hang
TI Motile Axonal Mitochondria Contribute to the Variability of Presynaptic
Strength
SO CELL REPORTS
LA English
DT Article
ID SYNAPTIC-TRANSMISSION; HIPPOCAMPAL SYNAPSES; QUANTAL SIZE; RELEASE;
NEURONS; PROBABILITY; HOMEOSTASIS; VESICLES; IMPACT; POOL
AB One of the most notable characteristics of synaptic transmission is the wide variation in synaptic strength in response to identical stimulation. In hippocampal neurons, approximately one-third of axonal mitochondria are highly motile, and some dynamically pass through presynaptic boutons. This raises a fundamental question: can motile mitochondria contribute to the pulse-to-pulse variability of presynaptic strength? Recently, we identified syntaphilin as an axonal mitochondrial-docking protein. Using hippocampal neurons and slices of syntaphilin knockout mice, we demonstrate that the motility of axonal mitochondria correlates with presynaptic variability. Enhancing mitochondrial motility increases the pulse-to-pulse variability, whereas immobilizing mitochondria reduces the variability. By dual-color live imaging at single-bouton levels, we further show that motile mitochondria passing through boutons dynamically influence synaptic vesicle release, mainly by altering ATP homeostasis in axons. Thus, our study provides insight into the fundamental properties of the CNS to ensure the plasticity and reliability of synaptic transmission.
C1 [Sun, Tao; Qiao, Haifa; Pan, Ping-Yue; Chen, Yanmin; Sheng, Zu-Hang] Natl Inst Neurol Disorders & Stroke, Synapt Funct Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Sheng, ZH (reprint author), Natl Inst Neurol Disorders & Stroke, Synapt Funct Sect, Porter Neurosci Res Ctr, NIH, Room 2B-215,35 Convent Dr, Bethesda, MD 20892 USA.
EM shengz@ninds.nih.gov
FU Intramural Research Program of NINDS, NIH
FX We thank J. Diamond, W. Lu, C.J. McBain, and L.-G. Wu for helpful
discussions, G. Yellen for the ATP sensor Perceval, J. di Giovanni and
B. Zhou for statistical analysis, the members of the Z.-H.S. lab for
technical assistance and discussion, and D. Schoenberg for editing. The
work was supported by the Intramural Research Program of NINDS, NIH (to
Z.-H.S.). T.S. conducted all imaging analysis. H.Q. conducted
electrophysiological analysis. P.-Y.P. did preliminary study on the
mouse model. Y.C. analyzed mitochondrial motility. Z.-H.S. is a senior
author who designed the project, coordinated experiments, and wrote the
manuscript.
NR 22
TC 52
Z9 54
U1 1
U2 13
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 AUG
PY 2013
VL 4
IS 3
BP 413
EP 419
DI 10.1016/j.celrep.2013.06.040
PG 7
WC Cell Biology
SC Cell Biology
GA 206SH
UT WOS:000323542200002
PM 23891000
ER
PT J
AU Ng, D
Johnston, JJ
Teer, JK
Singh, LN
Peller, LC
Wynter, JS
Lewis, KL
Cooper, DN
Stenson, PD
Mullikin, JC
Biesecker, LG
AF David Ng
Johnston, Jennifer J.
Teer, Jamie K.
Singh, Larry N.
Peller, Lindsey C.
Wynter, Jamila S.
Lewis, Katie L.
Cooper, David N.
Stenson, Peter D.
Mullikin, James C.
Biesecker, Leslie G.
CA NIH Intramural Sequencing Ctr NISC
TI Interpreting Secondary Cardiac Disease Variants in an Exome Cohort
SO CIRCULATION-CARDIOVASCULAR GENETICS
LA English
DT Article
DE arrhythmias, cardiac; cardiomyopathies; genetics; genetic variation;
genetic susceptibility; genomics; long QT syndrome
ID LONG-QT SYNDROME; BINDING PROTEIN-C; LEFT-VENTRICULAR NONCOMPACTION;
CANCER-SUSCEPTIBILITY GENES; HYPERTROPHIC CARDIOMYOPATHY; DILATED
CARDIOMYOPATHY; INCIDENTAL FINDINGS; UNRELATED PATIENTS; GENOMICS
RESEARCH; TASK-FORCE
AB Background
Massively parallel sequencing to identify rare variants is widely practiced in medical research and in the clinic. Genome and exome sequencing can identify the genetic cause of a disease (primary results), but it can also identify pathogenic variants underlying diseases that are not being sought (secondary or incidental results). A major controversy has developed surrounding the return of secondary results to research participants. We have piloted a method to analyze exomes to identify participants at risk for cardiac arrhythmias, cardiomyopathies, or sudden death.
Methods and Results
Exome sequencing was performed on 870 participants not selected for arrhythmia, cardiomyopathy, or a family history of sudden death. Exome data from 22 cardiac arrhythmia- and 41 cardiomyopathy-associated genes were analyzed using an algorithm that filtered results on genotype quality, frequency, and database information. We identified 1367 variants in the cardiomyopathy genes and 360 variants in the arrhythmia genes. Six participants had pathogenic variants associated with dilated cardiomyopathy (n=1), hypertrophic cardiomyopathy (n=2), left ventricular noncompaction (n=1), or long-QT syndrome (n=2). Two of these participants had evidence of cardiomyopathy and 1 had left ventricular noncompaction on echocardiogram. Three participants with likely pathogenic variants had prolonged QTc. Family history included unexplained sudden death among relatives.
Conclusions
Approximately 0.5% of participants in this study had pathogenic variants in known cardiomyopathy or arrhythmia genes. This high frequency may be due to self-selection, false positives, or underestimation of the prevalence of these conditions. We conclude that clinically important cardiomyopathy and dysrhythmia secondary variants can be identified in unselected exomes.
C1 [David Ng; Johnston, Jennifer J.; Teer, Jamie K.; Singh, Larry N.; Peller, Lindsey C.; Wynter, Jamila S.; Lewis, Katie L.; Biesecker, Leslie G.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
[Teer, Jamie K.; Mullikin, James C.; Biesecker, Leslie G.] NHGRI, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA.
[Mullikin, James C.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
[Cooper, David N.; Stenson, Peter D.] Cardiff Univ, Sch Med, Inst Med Genet, Cardiff CF10 3AX, S Glam, Wales.
RP Biesecker, LG (reprint author), NHGRI, Genet Dis Res Branch, 49 Convent Dr 4A56, Bethesda, MD 20892 USA.
EM lesb@helix.nih.gov
OI Cooper, David N./0000-0002-8943-8484
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.
NR 43
TC 28
Z9 28
U1 1
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1942-3268
J9 CIRC-CARDIOVASC GENE
JI Circ.-Cardiovasc. Genet.
PD AUG
PY 2013
VL 6
IS 4
BP 337
EP 346
DI 10.1161/CIRCGENETICS.113.000039
PG 10
WC Cardiac & Cardiovascular Systems; Genetics & Heredity
SC Cardiovascular System & Cardiology; Genetics & Heredity
GA 206SL
UT WOS:000323542700005
PM 23861362
ER
PT J
AU Mamasoula, C
Prentice, RR
Pierscionek, T
Pangilinan, F
Mills, JL
Druschel, C
Pass, K
Russell, MW
Hall, D
Topf, A
Brown, DL
Zelenika, D
Bentham, J
Cosgrove, C
Bhattacharya, S
Riveron, JG
Setchfield, K
Brook, JD
Bu'Lock, FA
Thornborough, C
Rahman, TJ
Doza, JP
Tan, HL
O'Sullivan, J
Stuart, AG
Blue, G
Winlaw, D
Postma, AV
Mulder, BJM
Zwinderman, AH
van Engelen, K
Moorman, AFM
Rauch, A
Gewillig, M
Breckpot, J
Devriendt, K
Lathrop, GM
Farrall, M
Goodship, JA
Cordell, HJ
Brody, LC
Keavney, BD
AF Mamasoula, Chrysovalanto
Prentice, R. Reid
Pierscionek, Tomasz
Pangilinan, Faith
Mills, James L.
Druschel, Charlotte
Pass, Kenneth
Russell, Mark W.
Hall, Darroch
Toepf, Ana
Brown, Danielle L.
Zelenika, Diana
Bentham, Jamie
Cosgrove, Catherine
Bhattacharya, Shoumo
Riveron, Javier Granados
Setchfield, Kerry
Brook, J. David
Bu'Lock, Frances A.
Thornborough, Chris
Rahman, Thahira J.
Doza, Julian Palomino
Tan, Huay L.
O'Sullivan, John
Stuart, A. Graham
Blue, Gillian
Winlaw, David
Postma, Alex V.
Mulder, Barbara J. M.
Zwinderman, Aelko H.
van Engelen, Klaartje
Moorman, Antoon F. M.
Rauch, Anita
Gewillig, Marc
Breckpot, Jeroen
Devriendt, Koen
Lathrop, G. Mark
Farrall, Martin
Goodship, Judith A.
Cordell, Heather J.
Brody, Lawrence C.
Keavney, Bernard D.
TI Association Between C677T Polymorphism of Methylene Tetrahydrofolate
Reductase and Congenital Heart Disease: Meta-Analysis of 7697 Cases and
13 125 Controls
SO CIRCULATION-CARDIOVASCULAR GENETICS
LA English
DT Article
DE congenital heart disease; folate; genetic association; Mendelian
randomization; MTHFR
ID MULTIVITAMIN SUPPLEMENTATION; FOLIC-ACID; DEFECTS; RISK; MTHFR; GENE;
PREVALENCE; VARIANT
AB Background
Association between the C677T polymorphism of the methylene tetrahydrofolate reductase (MTHFR) gene and congenital heart disease (CHD) is contentious.
Methods and Results
We compared genotypes between CHD cases and controls and between mothers of CHD cases and controls. We placed our results in context by conducting meta-analyses of previously published studies. Among 5814 cases with primary genotype data and 10 056 controls, there was no evidence of association between MTHFR C677T genotype and CHD risk (odds ratio [OR], 0.96 [95% confidence interval, 0.87-1.07]). A random-effects meta-analysis of all studies (involving 7697 cases and 13 125 controls) suggested the presence of association (OR, 1.25 [95% confidence interval, 1.03-1.51]; P=0.022) but with substantial heterogeneity among contributing studies (I-2=64.4%) and evidence of publication bias. Meta-analysis of large studies only (defined by a variance of the log OR <0.05), which together contributed 83% of all cases, yielded no evidence of association (OR, 0.97 [95% confidence interval, 0.91-1.03]) without significant heterogeneity (I-2=0). Moreover, meta-analysis of 1781 mothers of CHD cases (829 of whom were genotyped in this study) and 19 861 controls revealed no evidence of association between maternal C677T genotype and risk of CHD in offspring (OR, 1.13 [95% confidence interval, 0.87-1.47]). There was no significant association between MTHFR genotype and CHD risk in large studies from regions with different levels of dietary folate.
Conclusions
The MTHFR C677T polymorphism, which directly influences plasma folate levels, is not associated with CHD risk. Publication biases appear to substantially contaminate the literature with regard to this genetic association.
C1 [Mamasoula, Chrysovalanto; Pierscionek, Tomasz; Hall, Darroch; Toepf, Ana; Brown, Danielle L.; Rahman, Thahira J.; Doza, Julian Palomino; Tan, Huay L.; Goodship, Judith A.; Cordell, Heather J.; Keavney, Bernard D.] Newcastle Univ, Inst Med Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Prentice, R. Reid; Pangilinan, Faith; Brody, Lawrence C.] NHGRI, Mol Pathogenesis Sect, Genome Technol Branch, Bethesda, MD 20892 USA.
[Mills, James L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
[Druschel, Charlotte] New York State Dept Hlth, Congenital Malformat Registry, Troy, NY USA.
[Druschel, Charlotte] SUNY Albany, Dept Epidemiol & Biostat, Sch Publ Hlth, Rensselaer, NY USA.
[Pass, Kenneth] New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA.
[Russell, Mark W.] Univ Michigan, Sch Med, Dept Pediat & Communicable Dis, Ann Arbor, MI USA.
[Zelenika, Diana; Lathrop, G. Mark] CEA, Inst Genom, Ctr Natl Genotypage, Evry, France.
[Zelenika, Diana; Lathrop, G. Mark] Fdn Jean Dausset, Ctr Etud Polymorphisme Humain, Paris, France.
[Lathrop, G. Mark] McGill Univ, Montreal, PQ, Canada.
[Lathrop, G. Mark] Genome Quebec Innovat Ctr, Montreal, PQ, Canada.
[Bentham, Jamie; Cosgrove, Catherine; Bhattacharya, Shoumo; Farrall, Martin] Univ Oxford, Dept Cardiovasc Med, Oxford, England.
[Riveron, Javier Granados; Setchfield, Kerry; Brook, J. David] Univ Nottingham, Inst Genet, Nottingham NG7 2RD, England.
[Bu'Lock, Frances A.; Thornborough, Chris] Univ Hosp Leicester NHS Trust, East Midlands Congenital Heart Ctr, Leicester, Leics, England.
[O'Sullivan, John] Newcastle Upon Tyne Hosp NHS Fdn Trust, Newcastle Upon Tyne, Tyne & Wear, England.
[Stuart, A. Graham] Bristol Royal Hosp Children, Bristol, Avon, England.
[Blue, Gillian; Winlaw, David] Childrens Hosp Westmead, Westmead, NSW, Australia.
[Postma, Alex V.; Mulder, Barbara J. M.; Zwinderman, Aelko H.; van Engelen, Klaartje; Moorman, Antoon F. M.] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands.
[Rauch, Anita] Univ Zurich, Inst Med Genet, Zurich, Switzerland.
[Breckpot, Jeroen; Devriendt, Koen] Univ Louvain, Ctr Human Genet, Louvain, Belgium.
[Keavney, Bernard D.] Univ Manchester, Inst Cardiovasc Sci, Manchester M13 9NT, Lancs, England.
RP Keavney, BD (reprint author), Univ Manchester, Inst Cardiovasc Sci, 46 Grafton St, Manchester M13 9NT, Lancs, England.
EM lbrody@mail.nih.gov; bernard.keavney@manchester.ac.uk
RI Rauch, Anita/C-5568-2014; Winlaw, David/F-8365-2016;
OI Rauch, Anita/0000-0003-2930-3163; Gewillig, Marc/0000-0002-4595-5922;
Postma, Alex/0000-0003-4874-2487; Winlaw, David/0000-0001-8005-3361;
Tan, Huay Lin/0000-0002-6670-2668; Brook, John
David/0000-0002-5946-6740; Granados-Riveron, Javier
T./0000-0002-0368-225X
FU British Heart Foundation; Wellcome Trust [BH100708, 085475]; European
Union FP7 Program CHeartED [HEALTH-F2-2008-223040]; Netherlands Heart
Foundation; Heart Research UK; Intramural Research Programs of the
National Human Genome Research Institute; Eunice Kennedy Shriver
National Institute of Child Health and Human Development
FX This study was funded by the British Heart Foundation, the Wellcome
Trust (grant BH100708), the European Union FP7 Program CHeartED
(HEALTH-F2-2008-223040), the Netherlands Heart Foundation, Heart
Research UK, the Intramural Research Programs of the National Human
Genome Research Institute, and the Eunice Kennedy Shriver National
Institute of Child Health and Human Development. This study makes use of
data generated by the Wellcome Trust Case-Control Consortium 2, funded
by the Wellcome Trust under award 085475. The study sponsors had no role
in the study design; collection, analysis, and interpretation of data;
manuscript writing; or decision to submit the paper for publication.
NR 23
TC 9
Z9 10
U1 0
U2 18
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1942-3268
J9 CIRC-CARDIOVASC GENE
JI Circ.-Cardiovasc. Genet.
PD AUG
PY 2013
VL 6
IS 4
BP 347
EP 353
DI 10.1161/CIRCGENETICS.113.000191
PG 7
WC Cardiac & Cardiovascular Systems; Genetics & Heredity
SC Cardiovascular System & Cardiology; Genetics & Heredity
GA 206SL
UT WOS:000323542700006
PM 23876493
ER
PT J
AU Huggins, GS
Papandonatos, GD
Erar, B
Belalcazar, LM
Brautbar, A
Ballantyne, C
Kitabchi, AE
Wagenknecht, LE
Knowler, WC
Pownall, HJ
Wing, RR
Peter, I
McCaffery, JM
AF Huggins, Gordon S.
Papandonatos, George D.
Erar, Bahar
Belalcazar, L. Maria
Brautbar, Ariel
Ballantyne, Christie
Kitabchi, Abbas E.
Wagenknecht, Lynne E.
Knowler, William C.
Pownall, Henry J.
Wing, Rena R.
Peter, Inga
McCaffery, Jeanne M.
CA Genetics Subgrp Action Hlth Diabet
TI Do Genetic Modifiers of High-Density Lipoprotein Cholesterol and
Triglyceride Levels Also Modify Their Response to a Lifestyle
Intervention in the Setting of Obesity and Type-2 Diabetes Mellitus? The
Action for Health in Diabetes (Look AHEAD) Study
SO CIRCULATION-CARDIOVASCULAR GENETICS
LA English
DT Article
DE behavior therapy; cholesterylester transfer; genomics; lipoproteins;
physiological protein genetics; triglycerides
ID HEPATIC LIPASE; AHEAD TRIAL; CARDIOVASCULAR-DISEASE; PLASMA-LIPIDS;
RISK-FACTORS; LOCI; INDIVIDUALS; WEIGHT; ASSOCIATION; POLYMORPHISM
AB Background-High-density lipoprotein cholesterol (HDL-C) and triglycerides are cardiovascular risk factors susceptible to lifestyle behavior modification and genetics. We hypothesized that genetic variants identified by genome-wide association studies as associated with HDL-C or triglyceride levels modify 1-year treatment response to an intensive lifestyle intervention, relative to a usual care of diabetes mellitus support and education.
Methods and Results-We evaluated 82 single-nucleotide polymorphisms, which represent 31 loci demonstrated by genome-wide association studies to be associated with HDL-C and triglycerides, in 3561 participants who consented for genetic studies and met eligibility criteria. Variants associated with higher baseline HDL-C levels, cholesterol ester transfer protein (CETP) rs3764261 and hepatic lipase (LIPC) rs8034802, were found to be associated with HDL-C increases with intensive lifestyle intervention (P=0.0038 and 0.013, respectively) and had nominally significant treatment interactions (P=0.047 and 0.046, respectively). The fatty acid desaturase-2 rs1535 variant, associated with low baseline HDL-C (P=0.017), was associated with HDL-C increases with intensive lifestyle intervention (0.0037) and had a nominal treatment interaction (P=0.035). Apolipoprotein B (rs693) and LIPC (rs8034802) single-nucleotide polymorphisms showed nominally significant associations with HDL-C and triglyceride changes with intensive lifestyle intervention and a treatment interaction (P<0.05). Phosphatidylglycerophosphate synthase-1 single-nucleotide polymorphisms (rs4082919) showed the most significant triglyceride treatment interaction in the full cohort (P=0.0009).
Conclusions-This is the first study to identify genetic variants modifying lipid responses to a randomized lifestyle behavior intervention in overweight or obese individuals with diabetes mellitus. The effects of genetic factors on lipid changes may differ from the effects on baseline lipids and are modifiable by behavioral intervention.
C1 [Huggins, Gordon S.] Tufts Med Ctr, MCRI Ctr Translat Genom, Mol Cardiol Res Inst, Boston, MA 02111 USA.
[Papandonatos, George D.; Erar, Bahar] Brown Univ, Dept Biostat, Providence, RI 02912 USA.
[Belalcazar, L. Maria] Univ Texas Med Branch, Dept Med, Galveston, TX 77555 USA.
[Brautbar, Ariel; Ballantyne, Christie] Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
[Brautbar, Ariel] Marshfield Clin Fdn Med Res & Educ, Dept Med Genet, Marshfield, WI USA.
[Ballantyne, Christie] Methodist DeBakey Heart & Vasc Ctr, Ctr Cardiovasc Dis Prevent, Houston, TX USA.
[Kitabchi, Abbas E.] Univ Tennessee, Dept Med, Hlth Sci Ctr, Memphis, TN 38104 USA.
[Wagenknecht, Lynne E.] Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA.
[Knowler, William C.] NIDDK, Phoenix, AZ USA.
[Wing, Rena R.; McCaffery, Jeanne M.] Miriam Hosp, Dept Psychiat & Human Behav, Weight Control & Diabet Res Ctr, Providence, RI 02906 USA.
[Wing, Rena R.; McCaffery, Jeanne M.] Brown Med Sch, Providence, RI USA.
[Peter, Inga] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA.
RP Huggins, GS (reprint author), Tufts Med Ctr, MCRI Ctr Translat Genom, 800 Washington St, Boston, MA 02111 USA.
EM ghuggins@tuftsmedicalcenter.org
RI Papandonatos, George/J-2328-2014;
OI Papandonatos, George/0000-0001-6770-932X
FU NIDDK NIH HHS [P30 DK017047, U01 DK057136, U01 DK057131, R01 DK090043]
NR 34
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U1 0
U2 12
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1942-3268
J9 CIRC-CARDIOVASC GENE
JI Circ.-Cardiovasc. Genet.
PD AUG
PY 2013
VL 6
IS 4
BP 391
EP 399
DI 10.1161/CIRCGENETICS.113.000042
PG 9
WC Cardiac & Cardiovascular Systems; Genetics & Heredity
SC Cardiovascular System & Cardiology; Genetics & Heredity
GA 206SL
UT WOS:000323542700011
PM 23861364
ER
PT J
AU Britt, JP
Bonci, A
AF Britt, Jonathan P.
Bonci, Antonello
TI Optogenetic interrogations of the neural circuits underlying addiction
SO CURRENT OPINION IN NEUROBIOLOGY
LA English
DT Article
ID VENTRAL TEGMENTAL AREA; NUCLEUS-ACCUMBENS SYNAPSES; MIDBRAIN DOPAMINE
NEURONS; PERMEABLE AMPA RECEPTORS; CHOLINERGIC INTERNEURONS; IN-VIVO;
STRIATAL NEURONS; REWARD-SEEKING; BASAL GANGLIA; PROLONGED WITHDRAWAL
AB Exposure to addictive drugs can result in maladaptive alterations in neural circuit function. This review highlights recent progress made in identifying the organization, function, and cellular plasticity of the ventral tegmental area (VTA) and nucleus accumbens (NAc), two brain regions strongly implicated in substance use disorders. Emphasis is given to advances made with new research methodologies, particularly optogenetics, which have provided scientists with an unprecedented ability to map neural circuitry and pinpoint drug-induced synaptic modifications. A better understanding of these adaptive events will aid the development of pharmacological treatments for drug addiction and, more generally, further our understanding of motivated behaviors.
C1 [Britt, Jonathan P.; Bonci, Antonello] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Bonci, Antonello] Johns Hopkins Univ, Solomon H Snyder Neurosci Inst, Sch Med, Baltimore, MD 21205 USA.
[Bonci, Antonello] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94158 USA.
RP Bonci, A (reprint author), NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
EM antonello.bonci@nih.gov
RI Britt, Jonathan/D-8877-2011
OI Britt, Jonathan/0000-0003-3044-9565
FU Intramural Research Program of the National Institutes of Health,
National Institute on Drug Abuse
FX Authors are supported by the Intramural Research Program of the National
Institutes of Health, National Institute on Drug Abuse. We thank Dr.
Ross McDevitt for helpful editorial comments and the National Institute
on Drug Abuse Visual Media Department for help with the figures.
NR 84
TC 20
Z9 20
U1 0
U2 25
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0959-4388
J9 CURR OPIN NEUROBIOL
JI Curr. Opin. Neurobiol.
PD AUG
PY 2013
VL 23
IS 4
BP 539
EP 545
DI 10.1016/j.conb.2013.01.010
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA 204XJ
UT WOS:000323404300013
PM 23375167
ER
PT J
AU Volkow, ND
Wang, GJ
Tomasi, D
Baler, RD
AF Volkow, Nora D.
Wang, Gen-Jack
Tomasi, Dardo
Baler, Ruben D.
TI Unbalanced neuronal circuits in addiction
SO CURRENT OPINION IN NEUROBIOLOGY
LA English
DT Article
ID NORMALIZES CINGULATE ACTIVITY; DEEP BRAIN-STIMULATION; SALIENT COGNITIVE
TASK; VENTRAL TEGMENTAL AREA; MEDIUM SPINY NEURONS; DRUG-ADDICTION;
SUBTHALAMIC NUCLEUS; COCAINE ADDICTION; LATERAL HABENULA; DOPAMINE
NEURONS
AB Through sequential waves of drug-induced neurochemical stimulation, addiction co-opts the brain's neuronal circuits that mediate reward, motivation to behavioral inflexibility and a severe disruption of self-control and compulsive drug intake. Brain imaging technologies have allowed neuroscientists to map out the neural landscape of addiction in the human brain and to understand how drugs modify it.
C1 [Volkow, Nora D.; Baler, Ruben D.] NIDA, NIH, Bethesda, MD 20892 USA.
[Wang, Gen-Jack; Tomasi, Dardo] Brookhaven Natl Lab, Dept Biosci, Upton, NY 11973 USA.
RP Volkow, ND (reprint author), NIDA, NIH, Bethesda, MD 20892 USA.
EM nvokowl@nida.nih.gov
RI Tomasi, Dardo/J-2127-2015
FU Intramural NIH HHS [Z99 DA999999]
NR 100
TC 34
Z9 36
U1 4
U2 34
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0959-4388
J9 CURR OPIN NEUROBIOL
JI Curr. Opin. Neurobiol.
PD AUG
PY 2013
VL 23
IS 4
BP 639
EP 648
DI 10.1016/j.conb.2013.01.002
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 204XJ
UT WOS:000323404300026
PM 23434063
ER
PT J
AU Marchant, NJ
Li, X
Shaham, Y
AF Marchant, Nathan J.
Li, Xuan
Shaham, Yavin
TI Recent developments in animal models of drug relapse
SO CURRENT OPINION IN NEUROBIOLOGY
LA English
DT Article
ID COCAINE-SEEKING BEHAVIOR; NUCLEUS-ACCUMBENS SYNAPSES; MEDIAL PREFRONTAL
CORTEX; PERMEABLE AMPA RECEPTORS; CONTEXT-INDUCED RELAPSE; VENTRAL
TEGMENTAL AREA; ALCOHOL-SEEKING; RAT MODEL; ENVIRONMENTAL ENRICHMENT;
NONDRUG REINFORCEMENT
AB Drug craving and relapse to drug use during abstinence are defining features of addiction. Evidence indicates that drug craving and relapse in humans are often provoked by acute exposure to the self-administered drug, drug-associated cues, or stress. During the last two decades, this clinical scenario has been primarily studied at the preclinical level using the classical reinstatement model. However, a single preclinical model cannot capture the complicated nature of human drug relapse. Therefore, more recently, we and others have developed several other models to study different facets of human drug relapse. In this review, we introduce and discuss recent findings from these other relapse models, including incubation of drug craving, reacquisition and resurgence models, and punishment-based and conflict-based relapse models.
C1 [Marchant, Nathan J.; Li, Xuan; Shaham, Yavin] Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD USA.
RP Marchant, NJ (reprint author), Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD USA.
EM nathan.marchant@nih.gov; Yavin.shaham@nih.gov
RI shaham, yavin/G-1306-2014;
OI Marchant, Nathan/0000-0001-8269-0532
FU National Institute on Drug Abuse
FX Research was supported by the National Institute on Drug Abuse,
Intramural Research Program. The authors declare that they do not have
any conflicts of interest (financial or otherwise) related to the data
presented in this manuscript.
NR 87
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Z9 46
U1 0
U2 29
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0959-4388
J9 CURR OPIN NEUROBIOL
JI Curr. Opin. Neurobiol.
PD AUG
PY 2013
VL 23
IS 4
BP 675
EP 683
DI 10.1016/j.conb.2013.01.003
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 204XJ
UT WOS:000323404300031
PM 23374536
ER
PT J
AU Ho, JE
Larson, MG
Vasan, RS
Ghorbani, A
Cheng, S
Rhee, EP
Florez, JC
Clish, CB
Gerszten, RE
Wang, TJ
AF Ho, Jennifer E.
Larson, Martin G.
Vasan, Ramachandran S.
Ghorbani, Anahita
Cheng, Susan
Rhee, Eugene P.
Florez, Jose C.
Clish, Clary B.
Gerszten, Robert E.
Wang, Thomas J.
TI Metabolite Profiles During Oral Glucose Challenge
SO DIABETES
LA English
DT Article
ID BILE-ACID SYNTHESIS; INSULIN SENSITIVITY; TOLERANCE TEST; PLASMA;
APPROPRIATE; RESISTANCE; INDUCTION; DIAGNOSIS; GLYCEMIA; DISEASE
AB To identify distinct biological pathways of glucose metabolism, we conducted a systematic evaluation of biochemical changes after an oral glucose tolerance test (OGTT) in a community-based population. Metabolic profiling was performed on 377 nondiabetic Framingham Offspring cohort participants (mean age 57 years, 42% women, BMI 30 kg/m(2)) before and after OGTT. Changes in metabolite levels were evaluated with paired Student t tests, cluster-based analyses, and multivariable linear regression to examine differences associated with insulin resistance. Of 110 metabolites tested, 91 significantly changed with OGTT (P <= 0.0005 for all). Amino acids, B-hydroxybutyrate, and tricarboxylic acid cycle intermediates decreased after OGTT, and glycolysis products increased, consistent with physiological insulin actions. Other pathways affected by OGTT included decreases in serotonin derivatives, urea cycle metabolites, and B vitamins. We also observed an increase in conjugated, and a decrease in unconjugated, bile acids. Changes in p-hydroxybutyrate, isoleucine, lactate, and pyridoxate were blunted in those with insulin resistance. Our findings demonstrate changes in 91 metabolites representing distinct biological pathways that are perturbed in response to an OGTT. We also identify metabolite responses that distinguish individuals with and without insulin resistance. These findings suggest that unique metabolic phenotypes can be unmasked by OGTT in the prediabetic state. Diabetes 62:2689-2698, 2013
C1 [Ho, Jennifer E.; Larson, Martin G.; Vasan, Ramachandran S.; Cheng, Susan; Wang, Thomas J.] Framingham Heart Study Natl Heart Lung & Blood In, Framingham, MA USA.
[Ho, Jennifer E.; Larson, Martin G.; Vasan, Ramachandran S.; Cheng, Susan; Wang, Thomas J.] Boston Univ, Sch Med, Framingham, MA USA.
[Ho, Jennifer E.] Boston Univ, Med Ctr, Dept Med, Cardiovasc Med Sect, Boston, MA USA.
[Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Vasan, Ramachandran S.] Boston Univ, Dept Med, Div Cardiol & Prevent Med, Boston, MA 02215 USA.
[Ghorbani, Anahita; Gerszten, Robert E.; Wang, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiol Div,Dept Med, Boston, MA USA.
[Cheng, Susan] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiol, Boston, MA 02115 USA.
[Rhee, Eugene P.; Gerszten, Robert E.; Wang, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA USA.
[Rhee, Eugene P.] Harvard Univ, Massachusetts Gen Hosp, Dept Med, Div Renal, Boston, MA 02115 USA.
[Rhee, Eugene P.; Clish, Clary B.; Gerszten, Robert E.] Broad Inst Massachusetts Inst Technol & Harvard U, Cambridge, MA USA.
[Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Florez, Jose C.] Massachusetts Gen Hosp, Diabet Unit, Diabet Res Ctr, Boston, MA 02114 USA.
[Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
RP Wang, TJ (reprint author), Framingham Heart Study Natl Heart Lung & Blood In, Framingham, MA USA.
EM tjwang@partners.org
OI Larson, Martin/0000-0002-9631-1254; Ho, Jennifer/0000-0002-7987-4768;
Ramachandran, Vasan/0000-0001-7357-5970
FU National Institutes of Health [NO1-HC-25195, R01-DK-HL-081572]; American
Heart Association; Leducq Foundation; Ellison Foundation
FX This work was supported by the National Institutes of Health
(NO1-HC-25195 and R01-DK-HL-081572), the American Heart Association, the
Leducq Foundation, and the Ellison Foundation.
NR 38
TC 49
Z9 49
U1 1
U2 21
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
J9 DIABETES
JI Diabetes
PD AUG
PY 2013
VL 62
IS 8
BP 2689
EP 2698
DI 10.2337/db12-0754
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 191RU
UT WOS:000322431100014
PM 23382451
ER
PT J
AU Michaliszyn, SF
Bonadonna, RC
Sjaarda, LA
Lee, SJ
Farchoukh, L
Arslanian, SA
AF Michaliszyn, Sara F.
Bonadonna, Riccardo C.
Sjaarda, Lindsey A.
Lee, SoJung
Farchoukh, Lama
Arslanian, Silva A.
TI beta-Cell Lipotoxicity in Response to Free Fatty Acid Elevation in
Prepubertal Youth African American Versus Caucasian Contrast
SO DIABETES
LA English
DT Article
ID INDUCED INSULIN-SECRETION; LONG-TERM EXPOSURE; NONDIABETIC SUBJECTS;
PANCREATIC-ISLETS; SENSITIVITY; GLUCOSE; HUMANS; ADOLESCENTS; INFUSION
AB Prepubertal African American (AA) youth compared with their Caucasian (C) peers have higher insulin secretion, which correlates positively with free fatty acid (FFA) concentration. In our continued efforts to explain the racial disparity in insulinemia, and because FFAs modulate insulin secretion, we hypothesized that AA youth would have a greater response to FFA-induced beta-cell insulin secretion than C youth. We compared the short-term effects of FFA elevation on fasting and glucose-stimulated C-peptide-modeled insulin secretion in prepubertal normal-weight AA versus C peers during a 2-h hyperglycemic clamp (12.5 mmol/L) on two occasions:.1) infusion of normal saline and 2) infusion of 20% intralipid (IL). During IL infusion, insulin sensitivity (IS) declined comparably in AA and C youth. Glucose sensitivity of first- and second-phase insulin secretion showed a significant condition x race interaction being higher in AA youth. Disposition index, beta-cell function relative to IS, declined with IL infusion in AA and C youth, with a significantly greater decrease in Cs compared with AAs. In conclusion, AA and C prepubertal youth both demonstrated a decline in beta-cell function relative to IS during IL infusion, indicative of acute lipotoxicity. The greater decline in C youth compared with AAs may suggest that C youth are more susceptible to beta-cell lipotoxicity than AA youth, or alternatively, that AA youth are hypersensitive to FFA stimulation of beta-cell insulin secretion, consistent with our theory.
C1 [Michaliszyn, Sara F.; Lee, SoJung; Farchoukh, Lama; Arslanian, Silva A.] Univ Pittsburgh, Childrens Hosp Pittsburgh, Med Ctr, Div Weight Management, Pittsburgh, PA 15213 USA.
[Bonadonna, Riccardo C.] Univ Verona, Sch Med, Div Endocrinol & Metab Dis, I-37100 Verona, Italy.
[Bonadonna, Riccardo C.] Azienda Osped Univ Integrata, Verona, Italy.
[Sjaarda, Lindsey A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Arslanian, Silva A.] Childrens Hosp Pittsburgh, Div Pediat Endocrinol Metab & Diabet Mellitus, Pittsburgh, PA 15213 USA.
RP Arslanian, SA (reprint author), Univ Pittsburgh, Childrens Hosp Pittsburgh, Med Ctr, Div Weight Management, Pittsburgh, PA 15213 USA.
EM silva.arslanian@chp.edu
OI Michaliszyn, Sara/0000-0002-1176-9187
FU National Institutes of Health [R01-HD-27503, K24-HD-01357,
UL1-RR-024153, UL1-TR-000005]; Clinical and Translational Science Award;
Richard L. Day Endowed Chair from University of Pittsburgh Medical
Center; University of Verona; Italian Ministry of University and
Research PRIN [2008CJ7CTW_002]
FX The study was supported by the National Institutes of Health Grants
R01-HD-27503 (S.A.A.) and K24-HD-01357 (S.A.A.), and UL1-RR-024153 and
UL1-TR-000005 Clinical and Translational Science Award, the Richard L.
Day Endowed Chair (S.A.A.) from University of Pittsburgh Medical Center,
research funds from University of Verona, and the Italian Ministry of
University and Research PRIN 2008CJ7CTW_002 (R.C.B.).
NR 29
TC 4
Z9 4
U1 0
U2 1
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
EI 1939-327X
J9 DIABETES
JI Diabetes
PD AUG
PY 2013
VL 62
IS 8
BP 2917
EP 2922
DI 10.2337/db12-1664
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 191RU
UT WOS:000322431100038
PM 23557704
ER
PT J
AU Hanson, RL
Guo, TW
Muller, YL
Fleming, J
Knowler, WC
Kobes, S
Bogardus, C
Baler, LJ
AF Hanson, Robert L.
Guo, Tingwei
Muller, Yunhua L.
Fleming, Jamie
Knowler, William C.
Kobes, Sayuko
Bogardus, Clifton
Baler, Leslie J.
TI Strong Parent-of-Origin Effects in the Association of KCNQ1 Variants
With Type 2 Diabetes in American Indians
SO DIABETES
LA English
DT Article
ID PIMA-INDIANS; INSULIN-RESISTANCE; IMPRINTED GENES; SUSCEPTIBILITY;
MELLITUS; GLUCOSE; IDENTIFICATION; OBESITY; RISKS
AB Parent-of-origin effects were observed in an Icelandic population for several genetic variants associated with type 2 diabetes, including those in KLF14 (rs4731702), MOB2 (rs2334499), and KCNQ1 (rs2237892, rs231362). We analyzed parent-of-origin effects for these variants, along with two others in KCNQ1 identified in previous genome-wide association studies (rs2237895, rs2299620), in 7,351 Pima Indians from 4,549 nuclear families; 34% of participants had diabetes. In a subset of 287 normoglycemic individuals, acute insulin secretion was measured by an intravenous glucose tolerance test. Statistically significant (P < 0.05) parent-of-origin effects were seen for association with type 2 diabetes for all variants. The strongest effect was seen at rs2299620 in KCNQ1; the C allele was associated with increased diabetes when maternally derived (odds ratio [OR], 1.92; P = 4.1 X 10(-12)), but not when paternally derived (OR, 0.93; P = 0.47; P = 9.9 X 10(-6) for difference in maternal and paternal effects). A maternally derived C allele also was associated with a 28% decrease in insulin secretion (P = 0.002). This study confirms parent-of-origin effects in the association with type 2 diabetes for variants in KLF14, MOB2, and KCNQ1. In Pima Indians, the effect of maternally derived KCNQ1 variants appears to be mediated through decreased insulin secretion and is particularly strong, accounting for 4% of the variance in liability to diabetes.
C1 [Hanson, Robert L.; Guo, Tingwei; Muller, Yunhua L.; Fleming, Jamie; Knowler, William C.; Kobes, Sayuko; Bogardus, Clifton; Baler, Leslie J.] NIDDK, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ USA.
RP Hanson, RL (reprint author), NIDDK, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ USA.
EM rhanson@phx.niddk.nih.gov
RI Hanson, Robert/O-3238-2015
OI Hanson, Robert/0000-0002-4252-7068
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 31
TC 17
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U1 0
U2 9
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
J9 DIABETES
JI Diabetes
PD AUG
PY 2013
VL 62
IS 8
BP 2984
EP 2991
DI 10.2337/db12-1767
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 191RU
UT WOS:000322431100045
PM 23630301
ER
PT J
AU Ma, B
Xiong, XJ
Chen, C
Li, HP
Xu, XZ
Li, XG
Li, R
Chen, GZ
Dackor, RT
Zeldin, DC
Wang, DW
AF Ma, Ben
Xiong, Xiaojv
Chen, Chen
Li, Huaping
Xu, Xizhen
Li, Xuguang
Li, Rui
Chen, Guangzhi
Dackor, Ryan T.
Zeldin, Darryl C.
Wang, Dao Wen
TI Cardiac-Specific Overexpression of CYP2J2 Attenuates Diabetic
Cardiomyopathy in Male Streptozotocin-Induced Diabetic Mice
SO ENDOCRINOLOGY
LA English
DT Article
ID ACTIVATED PROTEIN-KINASE; NITRIC-OXIDE SYNTHASE; EPOXYGENASE-DERIVED
EICOSANOIDS; FRUCTOSE-TREATED RATS; NECROSIS-FACTOR-ALPHA;
EPOXYEICOSATRIENOIC ACIDS; SIGNALING PATHWAYS; SKELETAL-MUSCLE;
AMP-KINASE; HYPERPOLARIZING FACTOR
AB Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid to biologically active cis-epoxyeicosatrienoic acids, which have potent vasodilatory, antiinflammatory, antiapoptotic, and antidiabetes properties. Here, we showed the effects of cardiac-specific overexpression of CYP epoxygenase 2J2 (CYP2J2) on diabetic cardiomyopathy and insulin resistance in high-fat (HF) diet fed, low-dose streptozotocin-treated mice. Diabetic cardiomyopathy was induced by HF and streptozotocin in cardiac-specific CYP2J2 transgenic mice. Physiological parameters and systemic metabolic parameters were monitored using ELISA kits. Intraperitoneal injection glucose tolerance test and hyperinsulinemic-euglycemic clamp study were implied to indicate insulin resistance. Cardiac function was assessed by echocardiography and Millar catheter system. Real-time PCR and Western blotting were used in signal pathway detection. alpha MHC-CYP2J2 transgenic mice showed significantly lower plasma glucose and insulin levels, improved glucose tolerance, and increased cardiac glucose uptake. Furthermore, alpha MHC-CYP2J2 transgenic mice were significantly protected from HF-streptozotocin-induced diabetic cardiomyopathy. Strikingly, CYP2J2 overexpression attenuated myocardial hypertrophy induced by diabetes. We conclude that cardiac-specific overexpression of CYP2J2 significantly protects against diabetic cardiomyopathy, which may be due to improved cardiac insulin resistance, glucose uptake, and reversal of cardiac hypertrophy. Relevant mechanisms may include up-regulation of peroxisome proliferator-activated receptor gamma, activation of insulin receptor and AMP-activated protein kinase signaling pathways, and inhibition of nuclear factor of activated T cells c3 signal by enhanced atrial natriuretic peptide production. These results suggest that CYP2J2 epoxygenase metabolites likely play an important role in plasma glucose homeostasis, and enhancement of epoxyeicosatrienoic acids activation may serve as an effective therapeutic strategy to prevent diabetic cardiomyopathy.
C1 [Ma, Ben; Xiong, Xiaojv; Chen, Chen; Li, Huaping; Xu, Xizhen; Li, Xuguang; Li, Rui; Chen, Guangzhi; Wang, Dao Wen] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Inst Hypertens, Wuhan 430030, Peoples R China.
[Ma, Ben; Xiong, Xiaojv; Chen, Chen; Li, Huaping; Xu, Xizhen; Li, Xuguang; Li, Rui; Chen, Guangzhi; Wang, Dao Wen] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Internal Med, Wuhan 430030, Peoples R China.
[Dackor, Ryan T.; Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA.
RP Wang, DW (reprint author), Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Internal Med, 1095 Jiefang Ave, Wuhan 430030, Peoples R China.
EM dwwang@tjh.tjmu.edu.cn
RI Chen, Chen/B-2080-2014
FU 973 Program [2012CB518004]; Nature Science Foundation Committee
[30930039, 31130031]; National Institutes of Health Division of
Intramural Research, National Institute of Environmental Health Sciences
[Z01 ES025034]
FX This work was supported by the 973 Program Grant 2012CB518004, Nature
Science Foundation Committee Projects 30930039 and 31130031, and the
National Institutes of Health Division of Intramural Research, National
Institute of Environmental Health Sciences Grant Z01 ES025034.
NR 53
TC 16
Z9 16
U1 0
U2 11
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0013-7227
J9 ENDOCRINOLOGY
JI Endocrinology
PD AUG
PY 2013
VL 154
IS 8
BP 2843
EP 2856
DI 10.1210/en.2012-2166
PG 14
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 186SC
UT WOS:000322063900029
PM 23696562
ER
PT J
AU Kim, WG
Park, JW
Willingham, MC
Cheng, SY
AF Kim, Won Gu
Park, Jeong Won
Willingham, Mark C.
Cheng, Sheue-yann
TI Diet-Induced Obesity Increases Tumor Growth and Promotes Anaplastic
Change in Thyroid Cancer in a Mouse Model
SO ENDOCRINOLOGY
LA English
DT Article
ID HORMONE-BETA-RECEPTOR; BODY-MASS INDEX; LEPTIN RECEPTOR; CARCINOMA;
GENE; INFLAMMATION; PROGRESSION; STAT3; RISK; MICE
AB Recent epidemiological studies provide strong evidence suggesting obesity is a risk factor in several cancers, including thyroid cancer. However, the molecular mechanisms by which obesity increases the risk of thyroid cancer are poorly understood. In this study, we evaluated the effect of diet-induced obesity on thyroid carcinogenesis in a mouse model that spontaneously develops thyroid cancer (Thrb(PV/PV)Pten(+/-) mice). These mice harbor a mutated thyroid hormone receptor-beta (denoted as PV) and haplodeficiency of the Pten gene. A high-fat diet (HFD) efficiently induced the obese phenotype in ThrbThrb(PV/PV)Pten(+/-) mice after 15 weeks. Thyroid tumor growth was markedly greater and survival was significantly lower in ThrbThrb(PV/PV)Pten(+/-) mice fed an HFD than in controls fed a low-fat diet (LFD). The HFD increased thyroid tumor cell proliferation by increasing the protein levels of cyclin D1 and phosphorylated retinoblastoma protein to propel cell cycle progression. Histopathological analysis showed that the frequency of anaplasia of thyroid cancer was significantly greater (2.6-fold) in the HFD group than the LFD group. The HFD treatment led to an increase in parametrial/epididymal fat pad and elevated serum leptin levels in ThrbThrb(PV/PV)Pten(+/-) mice. Further molecular analyses indicated that the HFD induced more aggressive pathological changes that were mediated by increased activation of the Janus kinase 2-signaling transducer and activator of transcription 3 (STAT3) signaling pathway and induction of STAT3 target gene expression. Our findings demonstrate that diet-induced obesity exacerbates thyroid cancer progression in ThrbThrb(PV/PV)Pten(+/-) mice and suggest that the STAT3 signaling pathway could be tested as a potential target for the treatment of thyroid cancer.
C1 [Kim, Won Gu; Park, Jeong Won; Willingham, Mark C.; Cheng, Sheue-yann] NCI, Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Cheng, SY (reprint author), NCI, Mol Biol Lab, 37 Convent Dr,Room 5128, Bethesda, MD 20892 USA.
EM chengs@mail.nih.gov
OI Kim, Won Gu/0000-0002-8404-7759
NR 39
TC 20
Z9 21
U1 1
U2 9
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0013-7227
J9 ENDOCRINOLOGY
JI Endocrinology
PD AUG
PY 2013
VL 154
IS 8
BP 2936
EP 2947
DI 10.1210/en.2013-1128
PG 12
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 186SC
UT WOS:000322063900037
PM 23748362
ER
PT J
AU Thomas, R
McHale, CM
Lan, Q
Hubbard, AE
Zhang, LP
Vermeulen, R
Li, GL
Rappaport, SM
Yin, SN
Rothman, N
Smith, MT
AF Thomas, Reuben
McHale, Cliona M.
Lan, Qing
Hubbard, Alan E.
Zhang, Luoping
Vermeulen, Roel
Li, Guilan
Rappaport, Stephen M.
Yin, Songnian
Rothman, Nathaniel
Smith, Martyn T.
TI Global gene expression response of a population exposed to benzene: A
pilot study exploring the use of RNA-sequencing technology
SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
LA English
DT Article
DE benzene; RNA sequencing; gene expression; peripheral blood
ID SEQ; TRANSCRIPTS; GENOMES; BIOMART; KEGG; PROTEINS; LEUKEMIA; ARRAYS
AB The mechanism of toxicity of the leukemogen benzene is not entirely known. This pilot study used RNA-sequencing (RNA-seq) technology to examine the effect of benzene exposure on gene expression in peripheral blood mononuclear cells obtained from 10 workers occupationally exposed to high levels of benzene (5 ppm) in air and 10 matched unexposed control workers, from a large study (n = 125) in which gene expression was previously measured by microarray. RNA-seq is more sensitive and has a wider dynamic range for the quantification of gene expression. Further, it has the ability to detect novel transcripts and alternative splice variants. The main conclusions from our analysis of the 20 workers by RNA-seq are as follows: The Pearson correlation between the two technical replicates for the RNA-seq experiments was 0.98 and the correlation between RNA-seq and microarray signals for the 20 subjects was around 0.6. 60% of the transcripts with detected reads from the RNA-seq experiments did not have corresponding probes on the microarrays. Fifty-three percent of the transcripts detected by RNA-seq and 99% of those with probes on the microarray were protein-coding. There was a significant overlap (P < 0.05) in transcripts declared differentially expressed due to benzene exposure using the two technologies. About 20% of the transcripts declared differentially expressed using the RNA-seq data were non-coding transcripts. Six transcripts were determined (false-discovery rate < 0.05) to be alternatively spliced as a result of benzene exposure. Overall, this pilot study shows that RNA-seq can complement the information obtained by microarray in the analysis of changes in transcript expression from chemical exposures. (c) 2013 Wiley Periodicals, Inc.
C1 [Thomas, Reuben; McHale, Cliona M.; Hubbard, Alan E.; Zhang, Luoping; Rappaport, Stephen M.; Smith, Martyn T.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA.
[Lan, Qing; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
[Vermeulen, Roel] Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands.
[Li, Guilan; Yin, Songnian] Chinese Ctr Dis Control & Prevent, Inst Occupat Hlth & Poison Control, Beijing, Peoples R China.
RP Thomas, R (reprint author), Univ Calif Berkeley, Sch Publ Hlth, 50 Univ Hall, Berkeley, CA 94720 USA.
EM reuben.thomas@berkeley.edu
RI Vermeulen, Roel/F-8037-2011
OI Vermeulen, Roel/0000-0003-4082-8163
FU National Institutes of Environmental Health Sciences [P42ES004705];
National Cancer Institute
FX Grant sponsor: National Institutes of Environmental Health Sciences;
Grant number: P42ES004705 (to M. T. S); Grant sponsor: National Cancer
Institute (intramural funds).
NR 37
TC 4
Z9 4
U1 0
U2 19
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0893-6692
EI 1098-2280
J9 ENVIRON MOL MUTAGEN
JI Environ. Mol. Mutagen.
PD AUG
PY 2013
VL 54
IS 7
SI SI
BP 566
EP 573
DI 10.1002/em.21801
PG 8
WC Environmental Sciences; Genetics & Heredity; Toxicology
SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology
GA 201EU
UT WOS:000323124300010
PM 23907980
ER
PT J
AU Moore, LE
Karami, S
Steinmaus, C
Cantor, KP
AF Moore, Lee E.
Karami, Sara
Steinmaus, Craig
Cantor, Kenneth P.
TI Use of OMIC technologies to study arsenic exposure in human populations
SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
LA English
DT Review
DE arsenic; OMICS; epigenetics; transciptonics proteomics
ID HUMAN LUNG-CELLS; GENE-EXPRESSION PROFILES; BLADDER-CANCER; DNA
HYPOMETHYLATION; LEUKOCYTE DNA; SKIN-LESIONS; METHYLATION; SPECTROMETRY;
LYMPHOCYTES; BIOMARKER
AB Exposure to arsenic (As) in drinking water is a major health concern. More than 100 million individuals are exposed to levels over the current World Health Organization standard of 10 mu g/L worldwide. Arsenic is one of the few agents established as a human carcinogen prior to understanding its mechanism of carcinogenicity. OMIC technologies have enabled researchers to utilize agnostic approaches to explore new, unknown mechanisms through which As causes disease in exposed human populations. In this article, we present recent studies in which OMIC technologies have been used to explore differences in human biological samples to identify markers of exposure, disease susceptibility, and effect in As-exposed and/or diseased tissues. (c) 2013 Wiley Periodicals, Inc.
C1 [Moore, Lee E.; Karami, Sara; Cantor, Kenneth P.] US Natl Canc Inst, DCEG, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
[Steinmaus, Craig] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA.
RP Moore, LE (reprint author), US Natl Canc Inst, DCEG, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
EM moorele@mail.nih.gov
NR 43
TC 4
Z9 4
U1 1
U2 13
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0893-6692
J9 ENVIRON MOL MUTAGEN
JI Environ. Mol. Mutagen.
PD AUG
PY 2013
VL 54
IS 7
SI SI
BP 589
EP 595
DI 10.1002/em.21792
PG 7
WC Environmental Sciences; Genetics & Heredity; Toxicology
SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology
GA 201EU
UT WOS:000323124300012
PM 23893652
ER
PT J
AU Zahid, S
Khan, N
Branham, K
Othman, M
Karoukis, AJ
Sharma, N
Moncrief, A
Mahmood, MN
Sieving, PA
Swaroop, A
Heckenlively, JR
Jayasundera, T
AF Zahid, Sarwar
Khan, Naheed
Branham, Kari
Othman, Mohammad
Karoukis, Athanasios J.
Sharma, Nisha
Moncrief, Ashley
Mahmood, Mahdi N.
Sieving, Paul A.
Swaroop, Anand
Heckenlively, John R.
Jayasundera, Thiran
TI Phenotypic Conservation in Patients With X-Linked Retinitis Pigmentosa
Caused by RPGR Mutations
SO JAMA OPHTHALMOLOGY
LA English
DT Article
ID GTPASE REGULATOR RPGR; CONE-ROD DYSTROPHY; EXON ORF15; FAMILIES; GENE;
IDENTIFICATION; PROTEIN; LOCUS; CILIA; DEGENERATION
AB IMPORTANCE For patients with X-linked retinitis pigmentosa and clinicians alike, phenotypic variability can be challenging because it complicates counseling regarding patients' likely visual prognosis.
OBJECTIVE To evaluate the clinical findings from patients with X-linked retinitis pigmentosa with 13 distinct RPGR mutations and assess for phenotypic concordance or variability.
DESIGN Retrospective medical record review of data collected from 1985 to 2011.
SETTING Kellogg Eye Center, University of Michigan.
PATIENTS A total of 42 patients with X-linked retinitis pigmentosa with mutations in RPGR. Age at first visit ranged from 4 to 53 years, with follow-up ranging from 1 to 11 visits (median follow-up time, 5.5 years; range, 1.4-32.7 years, for 23 patients with >1 visit).
MAIN OUTCOMES AND MEASURES Clinical data assessed for concordance included visual acuity (VA), Goldmann visual fields (GVFs), and full-field electroretinography (ERG). Electroretinography phenotype (cone-rod vs rod-cone dysfunction) was defined by the extent of photopic vs scotopic abnormality. Qualitative GVF phenotype was determined by the GVF pattern, where central or peripheral loss suggested cone or rod dysfunction, respectively. Goldmann visual fields were also quantified and compared among patients.
RESULTS Each mutation was detected in 2 or more related or unrelated patients. Five mutations in 11 patients displayed strong concordance of VA, while 4 mutations in 16 patients revealed moderate concordance of VA. A definitive cone-rod or rod-cone ERG pattern consistent among patients was found in 6 of 13 mutations (46.2%); the remaining mutations were characterized by patients demonstrating both phenotypes or who had limited data or nonrecordable ERG values. Concordant GVF phenotypes (7 rod-cone pattern vs 4 cone-rod pattern) were seen in 11 of 13 mutations (84.6%). All 6 mutations displaying a constant ERG pattern within the mutation group revealed a GVF phenotype consistent with the ERG findings.
CONCLUSIONS AND RELEVANCE While VA and ERG phenotypes are concordant in only some patients carrying identical mutations, assessment of GVF phenotypes revealed stronger phenotypic conservation. Phenotypic concordance is important for establishing proper counseling of patients diagnosed as having X-linked retinitis pigmentosa, as well as for establishing accurate patient selection and efficacy monitoring in therapeutic trials.
C1 [Zahid, Sarwar; Khan, Naheed; Branham, Kari; Othman, Mohammad; Karoukis, Athanasios J.; Sharma, Nisha; Moncrief, Ashley; Mahmood, Mahdi N.; Heckenlively, John R.; Jayasundera, Thiran] Univ Michigan, Kellogg Eye Ctr, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA.
[Sieving, Paul A.; Swaroop, Anand] NEI, NIH, Bethesda, MD 20892 USA.
RP Jayasundera, T (reprint author), Univ Michigan, Kellogg Eye Ctr, 1000 Wall St, Ann Arbor, MI 48105 USA.
EM thiran@umich.edu
OI Swaroop, Anand/0000-0002-1975-1141
FU Foundation Fighting Blindness; National Eye Institute (Core Center for
Vision Research grant) [EY007003]
FX This research was supported by the Foundation Fighting Blindness and the
National Eye Institute (Core Center for Vision Research grant EY007003).
NR 36
TC 10
Z9 10
U1 0
U2 4
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 2168-6165
J9 JAMA OPHTHALMOL
JI JAMA Ophthalmol.
PD AUG
PY 2013
VL 131
IS 8
BP 1016
EP 1025
DI 10.1001/jamaophthalmol.2013.120
PG 10
WC Ophthalmology
SC Ophthalmology
GA 206WD
UT WOS:000323554700007
PM 23681342
ER
PT J
AU Willis, JR
Vitale, SE
Agrawal, Y
Ramulu, PY
AF Willis, Jeffrey R.
Vitale, Susan E.
Agrawal, Yuri
Ramulu, Pradeep Y.
TI Visual Impairment, Uncorrected Refractive Error, and Objectively
Measured Balance in the United States
SO JAMA OPHTHALMOLOGY
LA English
DT Article
ID OLDER-ADULTS; POSTURAL STABILITY; RISK-FACTORS; VESTIBULOOCULAR REFLEX;
SPORTING ACTIVITIES; PHYSICAL-ACTIVITY; FALLS; PEOPLE; POPULATION;
VISION
AB IMPORTANCE Further research is crucial to better understand the reason for falls in individuals with visual impairment (VI) and to develop appropriate fall prevention strategies.
OBJECTIVE To compare balance measures in individuals with normal vision, VI, and uncorrected refractive error (URE).
DESIGN AND SETTING Cross-sectional study based on a national survey sample.
PARTICIPANTS A total of 4590 adults, 40 years or older, participating in the 2001 through 2004 National Health and Nutrition Examination Survey.
MAIN OUTCOME MEASURES Participants completed tests of standing balance with eyes open or eyes closed on a firm or compliant (foam) surface. Eyes-closed testing on a foam surface primarily assessed vestibular balance by minimizing visual and proprioceptive inputs. The main outcome measure was time to balance failure on firm and foam surface testing. Participants also self-reported difficulty with falling during the last year.
RESULTS Failure during eyes-open balance testing conditions or eyes-closed balance testing on a firm surface was not more common among participants with VI-associated or URE-associated vision loss (P > .22). In eyes-closed foam surface balance testing, multivariable models demonstrated higher rates of balance loss with VI-associated vision loss (P = .02) and with URE-associated vision loss (P = .04) (hazard ratio, 1.7 per logarithm of the minimum angle of resolution [logMAR] unit change [10 lines] for both). Self-reported falling difficulty was associated with worse VI (odds ratio, 3.7 per logMAR unit change; P = .03) but not with worse URE (odds ratio, 3.4 per logMAR unit change; P = .14).
CONCLUSIONS AND RELEVANCE The vestibular contribution to balance (measured with eyes closed on a foam surface) was worse for individuals with VI or URE. Reduced visual inputs may weaken the vestibulo-ocular reflex, an important system that maintains the effectiveness of vestibular balance. Alternately, common degenerative pathways or lower physical activity levels may affect balance, particularly among those with VI.
C1 [Willis, Jeffrey R.; Vitale, Susan E.; Agrawal, Yuri; Ramulu, Pradeep Y.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21287 USA.
[Vitale, Susan E.] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
RP Ramulu, PY (reprint author), Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, 600 N Wolfe St,Maumenee Room B110, Baltimore, MD 21287 USA.
EM pramulu@jhmi.edu
NR 41
TC 11
Z9 11
U1 3
U2 13
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 2168-6165
J9 JAMA OPHTHALMOL
JI JAMA Ophthalmol.
PD AUG
PY 2013
VL 131
IS 8
BP 1049
EP 1056
DI 10.1001/jamaophthalmol.2013.316
PG 8
WC Ophthalmology
SC Ophthalmology
GA 206WD
UT WOS:000323554700011
PM 23744090
ER
PT J
AU Ward, BK
Agrawal, Y
Hoffman, HJ
Carey, JP
Della Santina, CC
AF Ward, Bryan K.
Agrawal, Yuri
Hoffman, Howard J.
Carey, John P.
Della Santina, Charles C.
TI Prevalence and Impact of Bilateral Vestibular Hypofunction Results From
the 2008 US National Health Interview Survey
SO JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY
LA English
DT Article
ID EPIDEMIOLOGY; POPULATION; DIZZINESS; VERTIGO
AB IMPORTANCE Profound bilateral vestibular hypofunction (BVH) causes disabling oscillopsia, chronic disequilibrium, and postural instability, but little is known about its epidemiology and impact.
OBJECTIVE To assess prevalence and functional impact of BVH in the US adult population.
DESIGN AND SETTING National cross-sectional survey using a national database and corollary validation study.
PATIENTS Adult respondents to the 2008 Balance and Dizziness Supplement to the US National Health Interview Survey (N = 21 782).
MAIN OUTCOMES AND MEASURES Prevalence of BVH, socioeconomic and quality-of-life impact of BVH, and fall risk. Criteria for the survey-based diagnosis of BVH included all of the following: presence of visual blurring with head movement; unsteadiness; difficulty walking in darkness or unsteady surfaces and in a straight path; and symptoms being at least "a big problem" and present for at least 1 year, in the absence of other neurologic conditions or eye pathologic conditions affecting vision.
RESULTS Adjusted national estimates from this survey indicate the prevalence of BVH in 2008 was 28 per 100 000 US adults (64 046 Americans). Of the participants with BVH, 44% reported changing their driving habits because of their symptoms, 56% reported reduced participation in social activities, and 58% reported difficulties with activities of daily living. Respondents with BVH had a 31-fold increase in the odds of falling in multivariate analyses compared with all respondents, with 25% reporting a recent fall-related injury.
CONCLUSIONS AND RELEVANCE As estimated by the presence of specific symptoms in a nationally representative survey, BVH has considerable socioeconomic and quality-of-life impacts and significantly increases fall risk. These data support the need for new therapeutic strategies for BVH, including vestibular rehabilitation and implantable vestibular prostheses.
C1 [Ward, Bryan K.; Agrawal, Yuri; Carey, John P.; Della Santina, Charles C.] Johns Hopkins Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21205 USA.
[Ward, Bryan K.; Agrawal, Yuri; Carey, John P.; Della Santina, Charles C.] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA.
[Hoffman, Howard J.] Natl Inst Deafness & Other Commun Disorders, Epidemiol & Stat Program, NIH, Bethesda, MD USA.
RP Ward, BK (reprint author), Johns Hopkins Outpatient Ctr, Dept Otolaryngol Head & Neck Surg, 601 N Caroline St,6th Floor, Baltimore, MD 21287 USA.
EM bward15@jhmi.edu
FU National Institute on Deafness and Other Communication Disorders (NIDCD)
[T32DC000027]; NIDCD [R01DC9255, R01DC2390]
FX During their work on this project, Dr Ward was supported by grant
T32DC000027 from the National Institute on Deafness and Other
Communication Disorders (NIDCD), and Dr Della Santina was supported by
grants R01DC9255 and R01DC2390 from the NIDCD.
NR 25
TC 17
Z9 18
U1 2
U2 7
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 2168-6181
J9 JAMA OTOLARYNGOL
JI JAMA Otolaryngol-Head Neck Surg.
PD AUG
PY 2013
VL 139
IS 8
BP 803
EP 810
DI 10.1001/jamaoto.2013.3913
PG 8
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA 206TM
UT WOS:000323545800008
PM 23949355
ER
PT J
AU Dunleavy, K
Wilson, WH
AF Dunleavy, Kieron
Wilson, Wyndham H.
TI Implications of the Shifting Pathobiology of AIDS-Related Lymphoma
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Editorial Material
ID INFUSIONAL EPOCH CHEMOTHERAPY; NON-HODGKIN-LYMPHOMA; B-CELL LYMPHOMA;
HIV
C1 [Dunleavy, Kieron; Wilson, Wyndham H.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Wilson, WH (reprint author), NCI, Metab Branch, Bldg 10,Rm 4N-115,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM wilsonw@mail.nih.gov
NR 14
TC 6
Z9 6
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 JNCI-J NATL CANCER I
JI JNCI-. Natl. Cancer Inst.
PD AUG
PY 2013
VL 105
IS 16
BP 1170
EP 1171
DI 10.1093/jnci/djt192
PG 2
WC Oncology
SC Oncology
GA 207YR
UT WOS:000323641300006
PM 23892361
ER
PT J
AU Horai, R
Silver, PB
Chen, J
Agarwal, RK
Chong, WP
Jittayasothorn, Y
Mattapallil, MJ
Nguyen, S
Natarajan, K
Villasmil, R
Wang, P
Karabekian, Z
Lytton, SD
Chan, CC
Caspi, RR
AF Horai, Reiko
Silver, Phyllis B.
Chen, Jun
Agarwal, Rajeev K.
Chong, Wai Po
Jittayasothorn, Yingyos
Mattapallil, Mary J.
Nguyen, Sonia
Natarajan, Kannan
Villasmil, Rafael
Wang, Peng
Karabekian, Zaruhi
Lytton, Simon D.
Chan, Chi-Chao
Caspi, Rachel R.
TI Breakdown of immune privilege and spontaneous autoimmunity in mice
expressing a transgenic T cell receptor specific for a retinal
autoantigen
SO JOURNAL OF AUTOIMMUNITY
LA English
DT Article
DE Autoimmune uveitis; Immune privilege; TCR transgenic mouse; Spontaneous
disease
ID NONOBESE DIABETIC MICE; NEO-SELF ANTIGEN; REGULATORY CELLS; BINDING
PROTEIN; DISEASE; UVEITIS; INFLAMMATION; TOLERANCE; EYE; UVEORETINITIS
AB Despite presence of circulating retina-specific T cells in healthy individuals, ocular immune privilege usually averts development of autoimmune uveitis. To study the breakdown of immune privilege and development of disease, we generated transgenic (Tg) mice that express a T cell receptor (TCR) specific for interphotoreceptor retinoid-binding protein (IRBP), which serves as an autoimmune target in uveitis induced by immunization. Three lines of TCR Tg mice, with different levels of expression of the transgenic R161 TCR and different proportions of IRBP-specific CD4(+) T cells in their peripheral repertoire, were successfully established. Importantly, two of the lines rapidly developed spontaneous uveitis, reaching 100% incidence by 2 and 3 months of age, respectively, whereas the third appeared "poised" and only developed appreciable disease upon immune perturbation. Susceptibility roughly paralleled expression of the R161 TCR In all three lines, peripheral CD4(+) T cells displayed a naive phenotype, but proliferated in vitro in response to IRBP and elicited uveitis upon adoptive transfer. In contrast, CD4(+) T cells infiltrating uveitic eyes mostly showed an effector/memory phenotype, and included Th1, Th17 as well as T regulatory cells that appeared to have been peripherally converted from conventional CD4(+) T cells rather than thymically derived. Thus, R161 mice provide a new and valuable model of spontaneous autoimmune disease that circumvents the limitations of active immunization and adjuvants, and allows to study basic mechanisms involved in maintenance and breakdown of immune homeostasis affecting immunologically privileged sites such as the eye. Published by Elsevier Ltd.
C1 [Horai, Reiko; Silver, Phyllis B.; Chen, Jun; Agarwal, Rajeev K.; Chong, Wai Po; Jittayasothorn, Yingyos; Mattapallil, Mary J.; Nguyen, Sonia; Wang, Peng; Karabekian, Zaruhi; Lytton, Simon D.; Chan, Chi-Chao; Caspi, Rachel R.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Natarajan, Kannan] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Villasmil, Rafael] NEI, Flow Cytometry Core, NIH, Bethesda, MD 20892 USA.
RP Horai, R (reprint author), NEI, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM hreiko@mail.nih.gov; caspir@mail.nih.gov
OI Lytton, Simon/0000-0001-5617-4139; Caspi, Rachel/0000-0002-7140-7671
FU NEI [EY000184]
FX We thank NEI Genetic Engineering Core for microinjection of TCR
transgenic constructs and assistance in maintaining the Tg mouse
colonies, NEI Histology Core for processing the slides and NEI Flow
Cytometry Core for assistances in cell sorting and analysis. We are
grateful to Drs. Hidehiro Yamane and William E. Paul for critical
reading of the manuscript. This work was supported by NEI intramural
funding, project # EY000184.
NR 44
TC 27
Z9 27
U1 1
U2 6
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0896-8411
J9 J AUTOIMMUN
JI J. Autoimmun.
PD AUG
PY 2013
VL 44
BP 21
EP 33
DI 10.1016/j.jaut.2013.06.003
PG 13
WC Immunology
SC Immunology
GA 208PJ
UT WOS:000323691300004
PM 23810578
ER
PT J
AU Arora, P
Wu, C
Khan, AM
Bloch, DB
Davis-Dusenbery, BN
Ghorbani, A
Spagnolli, E
Martinez, A
Ryan, A
Tainsh, LT
Kim, S
Rong, J
Huan, TX
Freedman, JE
Levy, D
Miller, KK
Hata, A
del Monte, F
Vandenwijngaert, S
Swinnen, M
Janssens, S
Holmes, TM
Buys, ES
Bloch, KD
Newton-Cheh, C
Wang, TJ
AF Arora, Pankaj
Wu, Connie
Khan, Abigail May
Bloch, Donald B.
Davis-Dusenbery, Brandi N.
Ghorbani, Anahita
Spagnolli, Ester
Martinez, Andrew
Ryan, Allicia
Tainsh, Laurel T.
Kim, Samuel
Rong, Jian
Huan, Tianxiao
Freedman, Jane E.
Levy, Daniel
Miller, Karen K.
Hata, Akiko
del Monte, Federica
Vandenwijngaert, Sara
Swinnen, Melissa
Janssens, Stefan
Holmes, Tara M.
Buys, Emmanuel S.
Bloch, Kenneth D.
Newton-Cheh, Christopher
Wang, Thomas J.
TI Atrial natriuretic peptide is negatively regulated by microRNA-425
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID BLOOD-PRESSURE; SODIUM-INTAKE; TARGETS; ASSOCIATION
AB Numerous common genetic variants have been linked to blood pressure, but no underlying mechanism has been elucidated. Population studies have revealed that the variant rs5068 (A/G) in the 3' untranslated region of NPPA, the gene encoding atrial natriuretic peptide (ANP), is associated with blood pressure. We selected individuals on the basis of rs5068 genotype (AG vs. AA) and fed them a low- or high-salt diet for 1 week, after which they were challenged with an intravenous saline infusion. On both diets, before and after saline administration, ANP levels were up to 50% higher in AG individuals than in AA individuals, a difference comparable. to the changes induced by high-salt diet or saline infusion. In contrast, B-type natriuretic peptide levels did not differ by rs5068 genotype. We identified a microRNA, miR-425, that is expressed in human atria and ventricles and is predicted to bind the sequence spanning rs5068 for the A, but not the G, allele. miR-425 silenced NPPA mRNA in an allele-specific manner, with the G allele conferring resistance to miR-425. This study identifies miR-425 as a regulator of ANP production, raising the possibility that miR-425 antagonists could be used to treat disorders of salt overload, including hypertension and heart failure.
C1 [Arora, Pankaj; Ghorbani, Anahita; Martinez, Andrew; Ryan, Allicia; Bloch, Kenneth D.; Newton-Cheh, Christopher; Wang, Thomas J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Arora, Pankaj; Ghorbani, Anahita; Bloch, Kenneth D.; Newton-Cheh, Christopher; Wang, Thomas J.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Arora, Pankaj; Martinez, Andrew; Ryan, Allicia; Kim, Samuel; Newton-Cheh, Christopher] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Arora, Pankaj; Newton-Cheh, Christopher] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Wu, Connie; Spagnolli, Ester; Tainsh, Laurel T.; Buys, Emmanuel S.; Bloch, Kenneth D.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Khan, Abigail May] Univ Penn, Sch Med, Div Cardiovasc Med, Philadelphia, PA 19104 USA.
[Bloch, Donald B.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Clin Immunol, Boston, MA 02114 USA.
[Bloch, Donald B.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA.
[Davis-Dusenbery, Brandi N.] Harvard Univ, Cambridge, MA 02138 USA.
[Rong, Jian; Huan, Tianxiao; Levy, Daniel] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Rong, Jian; Huan, Tianxiao; Levy, Daniel] Boston Univ, Sch Med, Framingham, MA USA.
[Rong, Jian; Huan, Tianxiao; Levy, Daniel] NHLBI, Ctr Populat Studies, NIH, Bethesda, MD 20892 USA.
[Rong, Jian; Huan, Tianxiao; Levy, Daniel] NHLBI, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Freedman, Jane E.] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA.
[Miller, Karen K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Div Endocrinol, Boston, MA 02114 USA.
[Hata, Akiko] UCSF, Cardiovasc Res Inst, San Francisco, CA USA.
[del Monte, Federica] Beth Israel Deaconess Med Ctr, Cardiovasc Inst, Boston, MA 02215 USA.
[Vandenwijngaert, Sara; Swinnen, Melissa; Janssens, Stefan] Univ Louvain, Univ Hosp Gasthuisberg, Dept Cardiovasc Sci, Louvain, Belgium.
[Holmes, Tara M.] Massachusetts Gen Hosp, Clin Res Ctr, Boston, MA 02114 USA.
[Wang, Thomas J.] Vanderbilt Univ, Div Cardiovasc Med, Nashville, TN 37232 USA.
RP Bloch, KD (reprint author), Anesthesia Ctr Crit Care Res, Dept Anesthesia & Crit Care, Jackson 4,55 Fruit St, Boston, MA 02114 USA.
EM kdbloch@partners.org; cnewtoncheh@chgr.mgh.harvard.edu;
thomas.j.wang@vanderbilt.edu
RI Huan, Tianxiao/D-6020-2014; Davis-Dusenbery, Brandi/N-2798-2013;
OI Davis-Dusenbery, Brandi/0000-0001-7811-8613; Arora,
Pankaj/0000-0003-2420-3550
FU NIH [R01-HL098283]; National Center for Research Resources [1
UL1-RR025758-01]; Fondation LeDucq; Research Council of the University
of Leuven [PF/10/014]
FX The authors thank the Massachusetts General Hospital Clinical Research
Center staff and the Center for Human Genetic Research extraction and
genotyping core. We also acknowledge support from NIH R01-HL098283 and 1
UL1-RR025758-01 from the National Center for Research Resources. The
research was also supported by a grant from the Fondation LeDucq and
from the Research Council of the University of Leuven (PF/10/014).
NR 13
TC 40
Z9 42
U1 0
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
J9 J CLIN INVEST
JI J. Clin. Invest.
PD AUG
PY 2013
VL 123
IS 8
BP 3378
EP 3382
DI 10.1172/JCI67383
PG 5
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 196CH
UT WOS:000322750500021
PM 23867623
ER
PT J
AU Iyer, S
Ambrogini, E
Bartell, SM
Han, L
Roberson, PK
de Cabo, R
Jilka, RL
Weinstein, RS
O'Brien, CA
Manolagas, SC
Almeida, M
AF Iyer, Srividhya
Ambrogini, Elena
Bartell, Shoshana M.
Han, Li
Roberson, Paula K.
de Cabo, Rafael
Jilka, Robert L.
Weinstein, Robert S.
O'Brien, Charles A.
Manolagas, Stavros C.
Almeida, Maria
TI FOXOs attenuate bone formation by suppressing Wnt signaling
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID STEM-CELL HOMEOSTASIS; OXIDATIVE STRESS; BETA-CATENIN; TRANSCRIPTION
FACTORS; OSTEOBLAST PROGENITORS; OSTEOCLAST FORMATION; GENE-EXPRESSION;
CYCLIN D1; C-ELEGANS; LIFE-SPAN
AB Wnt/beta-catenin/TCF signaling stimulates bone formation and suppresses adipogenesis. The hallmarks of skeletal involution with age, on the other hand, are decreased bone formation and increased bone marrow adiposity. These changes are associated with increased oxidative stress and decreased growth factor production, which activate members of the FOXO family of transcription factors. FOXOs in turn attenuate Wnt/beta-catenin signaling by diverting beta-catenin from TCF- to FOXO-mediated transcription. We show herein that mice lacking Foxo1, -3, and -4 in bipotential progenitors of osteoblast and adipocytes (expressing Osterixl) exhibited increased osteoblast number and high bone mass that was maintained in old age as well as decreased adiposity in the aged bone marrow. The increased bone mass in the Foxo-deficient mice was accounted for by increased proliferation of osteoprogenitor cells and bone formation resulting from upregulation of Wnt/beta-catenin signaling and cyclin D1 expression, but not changes in redox balance. Consistent with this mechanism, beta-catenin deletion in Foxo null cells abrogated both the increased cyclin D1 expression and proliferation. The elucidation of a restraining effect of FOXOs on Wnt signaling in bipotential progenitors suggests that FOXO activation by accumulation of age-associated cellular stressors may be a seminal pathogenetic mechanism in the development of involutional osteoporosis.
C1 [Iyer, Srividhya; Ambrogini, Elena; Bartell, Shoshana M.; Han, Li; Jilka, Robert L.; Weinstein, Robert S.; O'Brien, Charles A.; Manolagas, Stavros C.; Almeida, Maria] Univ Arkansas Med Sci, Ctr Osteoporosis & Metab Bone Dis, Div Endocrinol & Metab, Little Rock, AR 72205 USA.
[Iyer, Srividhya; Ambrogini, Elena; Bartell, Shoshana M.; Han, Li; Jilka, Robert L.; Weinstein, Robert S.; O'Brien, Charles A.; Manolagas, Stavros C.; Almeida, Maria] Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA.
[Roberson, Paula K.] Univ Arkansas Med Sci, Dept Biostat, Little Rock, AR 72205 USA.
[de Cabo, Rafael] NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA.
RP Almeida, M (reprint author), 4301 W Markham St,587, Little Rock, AR 72205 USA.
EM schullermaria@uams.edu
RI de Cabo, Rafael/J-5230-2016;
OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693
FU NIH [R01 AR56679, P01 AG13918, R01 AR49794, F32 AR061956]; Department of
Veterans Affairs grants from the Biomedical Laboratory Research and
Development Service of the VA Office of Research and Development [I01
BX000514, I01 BX000436, I01 BX000294, I01 BX001405]; University of
Arkansas for Medical Sciences Translational Research Institute; Tobacco
Settlement funds; University of Pisa, Italy; Intramural Research Program
of the National Institute on Aging
FX This work was supported by the NIH (R01 AR56679, P01 AG13918, and R01
AR49794, F32 AR061956); Department of Veterans Affairs grants from the
Biomedical Laboratory Research and Development Service of the VA Office
of Research and Development to R.L. Jilka. (I01 BX000514), RS. Weinstein
(I01 BX000436), C.A. O'Brien (I01 BX000294), and S.C. Manolagas (I01
BX001405); the University of Arkansas for Medical Sciences Translational
Research Institute and Tobacco Settlement funds. E. Ambrogini was
supported by a fellowship from the University of Pisa, Italy. R. de Cabo
is funded by the Intramural Research Program of the National Institute
on Aging. We are grateful to R. DePinho for providing the
Foxo1,-3,-4f/f and Foxo3f/f mice. We thank A.
Warren, A. DeLoose, S. Berryhill, and J. Crawford for technical
assistance and Leah Elrod for help with the preparation of the
manuscript.
NR 63
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Z9 52
U1 1
U2 19
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD AUG
PY 2013
VL 123
IS 8
BP 3409
EP 3419
DI 10.1172/JCI68049
PG 11
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 196CH
UT WOS:000322750500025
PM 23867625
ER
PT J
AU Ishikawa, T
Yuhanna, IS
Umetani, J
Lee, WR
Korach, KS
Shaul, PW
Umetani, M
AF Ishikawa, Tomonori
Yuhanna, Ivan S.
Umetani, Junko
Lee, Wan-Ru
Korach, Kenneth S.
Shaul, Philip W.
Umetani, Michihisa
TI LXR beta/estrogen receptor-alpha signaling in lipid rafts preserves
endothelial integrity
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID LIVER-X-RECEPTOR; NITRIC-OXIDE SYNTHASE; BREAST-CANCER GROWTH;
ESTROGEN-RECEPTOR; NUCLEAR RECEPTORS; DEFICIENT MICE; IN-VIVO;
ATHEROSCLEROSIS; BETA; CHOLESTEROL
AB Liver X receptors (LXR) are stimulated by cholesterol-derived oxysterols and serve as transcription factors to regulate gene expression in response to alterations in cholesterol. In the present study, we investigated the role of LXRs in vascular endothelial cells (ECs) and discovered that LXR beta has nonnuclear function and stimulates EC migration by activating endothelial NOS (eNOS). This process is mediated by estrogen receptor-alpha (ER alpha). LXR activation promoted the direct binding of LXR beta to the ligand-binding domain of ER alpha and initiated an extranuclear signaling cascade that requires ER alpha Ser118 phosphorylation by PI3K/AKT. Further studies revealed that LXR beta and ER alpha are colocalized and functionally coupled in EC plasma membrane caveolae/lipid. rafts. In isolated aortic rings, LXR activation of NOS caused relaxation, while in mice, LXR activation stimulated carotid artery reendothelialization via LXR beta- and ER alpha-dependent processes. These studies demonstrate that LXR beta has nonnuclear function in EC caveolae/lipid rafts that entails crosstalk with ER alpha, which promotes NO production and maintains endothelial monolayer integrity in vivo.
C1 [Ishikawa, Tomonori; Yuhanna, Ivan S.; Umetani, Junko; Lee, Wan-Ru; Shaul, Philip W.; Umetani, Michihisa] Univ Texas SW Med Ctr Dallas, Dept Pediat, Div Pulm & Vasc Biol, Dallas, TX 75390 USA.
[Korach, Kenneth S.] NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA.
[Umetani, Michihisa] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA.
RP Umetani, M (reprint author), Univ Texas SW Med Ctr Dallas, Dept Pediat, Div Pulm & Vasc Biol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
EM Michihisa.Umetani@utsouthwestern.edu
OI Korach, Kenneth/0000-0002-7765-418X
FU American Heart Association [0865158F]; NIH [HL087564]; Lowe Foundation
FX The authors thank K. Chambliss, C. Mineo, K. Kamm, K. Luby-Phelps, and
K. Rothberg for help on experiments; C.-J. Edgell for providing EA.hy926
cells; D. Mangelsdorf and S. Kliewer for critical review of the
manuscript; and members of the Shaul and Mango/Kliewer labs for helpful
suggestions. This work was supported by grants from the American Heart
Association (0865158F to M. Umetani), the NIH (HL087564 to P.W. Shaul),
and the Lowe Foundation (to P.W. Shaul).
NR 53
TC 12
Z9 12
U1 2
U2 9
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD AUG
PY 2013
VL 123
IS 8
BP 3488
EP 3497
DI 10.1172/JCI66533
PG 10
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 196CH
UT WOS:000322750500031
PM 23867501
ER
PT J
AU May, LA
Kramarenko, II
Brandon, CS
Voelkel-Johnson, C
Roy, S
Truong, K
Francis, SP
Monzack, EL
Lee, FS
Cunningham, LL
AF May, Lindsey A.
Kramarenko, Inga I.
Brandon, Carlene S.
Voelkel-Johnson, Christina
Roy, Soumen
Kristy Truong
Francis, Shimon P.
Monzack, Elyssa L.
Lee, Fu-Shing
Cunningham, Lisa L.
TI Inner ear supporting cells protect hair cells by secreting HSP70
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID HEAT-SHOCK PROTEINS; GROWTH-FACTOR RECEPTOR; INDUCED HEARING-LOSS;
STRESS-PROTEINS; IN-VITRO; HEAT-SHOCK-PROTEIN-70; DEATH; PATHWAY;
RELEASE; GLIA
AB Mechanosensory hair cells are the receptor cells of hearing and balance. Hair cells are sensitive to death from exposure to therapeutic drugs with ototoxic side effects, including aminoglycoside antibiotics and cisplatin. We recently showed that the induction of heat shock protein 70 (HSP70) inhibits ototoxic drug-induced hair cell death. Here, we examined the mechanisms underlying the protective effect of HSP70. In response to heat shock, HSP70 was induced in glia-like supporting cells but not in hair cells. Adenovirus-mediated infection of supporting cells with Hsp70 inhibited hair cell death. Coculture with heat-shocked utricles protected nonheat-shocked utricles against hair cell death. When heat-shocked utricles from Hsp70(-/-) mice were used in cocultures, protection was abolished in both the heat-shocked utricles and the nonheat-shocked utricles. HSP70 was detected by ELISA in the media surrounding heat-shocked utricles, and depletion of HSP70 from the media abolished the protective effect of heat shock, suggesting that HSP70 is secreted by supporting cells. Together our data indicate that supporting cells mediate the protective effect of HSP70 against hair cell death, and they suggest a major role for supporting cells in determining the fate of hair cells exposed to stress.
C1 [May, Lindsey A.; Roy, Soumen; Kristy Truong; Monzack, Elyssa L.; Cunningham, Lisa L.] Natl Inst Deafness & Other Commun Disorders, NIH, Rockville, MD 20850 USA.
[Kramarenko, Inga I.; Brandon, Carlene S.; Voelkel-Johnson, Christina; Francis, Shimon P.; Lee, Fu-Shing] Med Univ S Carolina, Charleston, SC 29425 USA.
[Francis, Shimon P.] Univ Virginia, Charlottesville, VA USA.
RP Cunningham, LL (reprint author), Natl Inst Deafness & Other Commun Disorders, NIH, 5 Res Ct, Rockville, MD 20850 USA.
EM Lisa.cunningham@nih.gov
FU NIH [5R01 DC007613, DC07613-SI]; NIH/NIDCD Division of Intramural
Research [ZIA DC 000079]
FX This work was supported by grants from the NIH (5R01 DC007613 and
DC07613-SI) and the NIH/NIDCD Division of Intramural Research (ZIA DC
000079). The authors are grateful to Jonathan Gale for many helpful
discussions about supporting cells. Our thanks to Thomas Friedman,
Andrew Griffith, and Matthew Kelley for helpful comments on the
manuscript.
NR 52
TC 27
Z9 27
U1 2
U2 14
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD AUG
PY 2013
VL 123
IS 8
BP 3577
EP 3587
DI 10.1172/JCI68480
PG 11
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 196CH
UT WOS:000322750500038
PM 23863716
ER
PT J
AU Michaud, CR
Ragland, DR
St Claire, MC
Elkins, WR
Gozalo, AS
AF Michaud, C. R.
Ragland, D. R.
St Claire, M. C.
Elkins, W. R.
Gozalo, A. S.
TI Mucinous Cystadenoma in the Lung of a Captiveborn Moustached Tamarin
(Saguinus mystax)
SO JOURNAL OF COMPARATIVE PATHOLOGY
LA English
DT Article
DE immunohistochemistry; moustached tamarin; pulmonary cystadenoma;
surfactant proteins
ID BORDERLINE MALIGNANCY; CYSTIC TUMOR
AB A 2-year-old, captive-born, male moustached tamarin was subjected to necropsy examination after a fatal head trauma. A solitary, circumscribed, subpleural mass (0.6 cm diameter) was found in the right caudal lung lobe. The mass was diagnosed as a mucinous cystadenoma. Histochemical and immunohistochemical tests were performed to further characterize the tumour. Surfactant proteins A, B, C and D were not found in the neoplastic cells, suggesting that the tumour arose from a non-surfactant-producing alveolar lining cell. Pulmonary mucinous cystadenomas are uncommon benign tumours in man and have not been reported previously in animals. Published by Elsevier Ltd.
C1 [Michaud, C. R.; Elkins, W. R.; Gozalo, A. S.] NIAID, Comparat Med Branch, NIH, Bethesda, MD 20892 USA.
[Ragland, D. R.; St Claire, M. C.] NIAID, Div Clin Res, NIH, Bethesda, MD 20892 USA.
[Ragland, D. R.] Charles River Labs, Germantown, MD USA.
RP Gozalo, AS (reprint author), NIAID, Comparat Med Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM gozaloa@niaid.nih.gov
FU National Institutes of Health, National Institute of Allergy and
Infectious Diseases (NIAID), Comparative Medicine Branch; Office of
Research Services
FX This study was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Allergy and
Infectious Diseases (NIAID), Comparative Medicine Branch and the Office
of Research Services. We thank Dr. R. Purcell and Dr. S. Emerson for
kindly letting us use tamarin tissue samples from a previous study.
NR 21
TC 0
Z9 0
U1 1
U2 4
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0021-9975
J9 J COMP PATHOL
JI J. Comp. Pathol.
PD AUG-OCT
PY 2013
VL 149
IS 2-3
BP 376
EP 380
DI 10.1016/j.jcpa.2012.12.001
PG 5
WC Pathology; Veterinary Sciences
SC Pathology; Veterinary Sciences
GA 207HO
UT WOS:000323589700033
PM 23356933
ER
PT J
AU Morton, FB
Lee, PC
Buchanan-Smith, HM
Brosnan, SF
Thierry, B
Paukner, A
de Waal, FBM
Widness, J
Essler, JL
Weiss, A
AF Morton, F. Blake
Lee, Phyllis C.
Buchanan-Smith, Hannah M.
Brosnan, Sarah F.
Thierry, Bernard
Paukner, Annika
de Waal, Frans B. M.
Widness, Jane
Essler, Jennifer L.
Weiss, Alexander
TI Personality Structure in Brown Capuchin Monkeys (Sapajus apella):
Comparisons With Chimpanzees (Pan troglodytes), Orangutans (Pongo spp.),
and Rhesus Macaques (Macaca mulatta)
SO JOURNAL OF COMPARATIVE PSYCHOLOGY
LA English
DT Article
DE temperament; animal; conscientiousness; phylogeny; New World monkey;
platyrrhine
ID EXPLORATORY FACTOR-ANALYSIS; INDIVIDUAL SPATIAL CHOICE; CEBUS-APELLA;
FORAGING GROUPS; ANIMAL PERSONALITIES; SOCIAL RELATIONSHIPS; CONSENSUAL
VALIDITY; TEMPORAL STABILITY; 5-FACTOR MODEL; SPOUSE-REPORTS
AB Species comparisons of personality structure (i.e., how many personality dimensions and the characteristics of those dimensions) can facilitate questions about the adaptive function of personality in nonhuman primates. Here we investigate personality structure in the brown capuchin monkey (Sapajus apella), a New World primate species, and compare this structure to those of chimpanzees (Pan troglodytes), orangutans (Pongo spp.), and rhesus macaques (Macaca mulatta). Brown capuchins evolved behavioral and cognitive traits that are qualitatively similar to those of great apes, and individual differences in behavior and cognition often reflect differences in personality. Thus, we hypothesized that brown capuchin personality structure would overlap more with great apes than with rhesus macaques. We obtained personality ratings from seven sites, including 127 brown capuchin monkeys. Principal-components analysis identified five personality dimensions (Assertiveness, Openness, Neuroticism, Sociability, and Attentiveness), which were reliable across raters and, in a subset of subjects, significantly correlated with relevant behaviors up to a year later. Comparisons between species revealed that brown capuchins and great apes overlapped in personality structure, particularly chimpanzees in the case of Neuroticism. However, in some respects (i.e., capuchin Sociability and Openness) the similarities between capuchins and great apes were not significantly greater than those between capuchins and rhesus macaques. We discuss the relevance of our results to brown capuchin behavior and the evolution of personality structure in primates.
C1 [Morton, F. Blake; Lee, Phyllis C.; Buchanan-Smith, Hannah M.] Univ Stirling, Sch Nat Sci, Behav & Evolut Res Grp, Stirling FK9 4LA, Scotland.
[Morton, F. Blake; Lee, Phyllis C.; Buchanan-Smith, Hannah M.] Univ Stirling, Sch Nat Sci, Scottish Primate Res Grp, Stirling FK9 4LA, Scotland.
[Brosnan, Sarah F.] Georgia State Univ, Dept Psychol, Atlanta, GA 30303 USA.
[Brosnan, Sarah F.] Georgia State Univ, Language Res Ctr, Atlanta, GA 30303 USA.
[Thierry, Bernard] Univ Strasbourg, CNRS, IPHC, Dept Ecol Physiol & Ethol, Strasbourg, France.
[Paukner, Annika] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Comparat Ethol Lab, NIH, Dept Hlth & Human Serv, Poolesville, MD USA.
[de Waal, Frans B. M.] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA.
[Widness, Jane] Yale Univ, Comparat Cognit Lab, Dept Psychol, New Haven, CT 06520 USA.
[Essler, Jennifer L.] Bucknell Univ, Dept Anim Behav, Lewisburg, PA 17837 USA.
[Weiss, Alexander] Univ Edinburgh, Dept Psychol, Sch Philosophy Psychol & Language Sci, Scottish Primate Res Grp, Edinburgh, Midlothian, Scotland.
RP Morton, FB (reprint author), Univ Stirling, Sch Nat Sci, Behav & Evolut Res Grp, Stirling FK9 4LA, Scotland.
EM Morton.blake@gmail.com
RI Buchanan-Smith, Hannah/A-5350-2009;
OI Buchanan-Smith, Hannah/0000-0002-2516-7734; Lee,
Phyllis/0000-0002-4296-3513
FU Charles A. Lockwood Memorial Fund; University of Stirling
FX We are very grateful to the people who completed personality
questionnaires: M. Baranay, A. Bates, S. Bower, D. Bryson, S. Calcutt,
N. Cladiere, C. Fruteau, J. Griffey, B. Herman, H. Kuroshima, G. Long,
T. McKenney, E. Messer, N. Moratscheck, C. Morin, C. Nisbitt, A.
Parrish, D. Proctor, M. Pel, D. Rice, T. Rubin, S. Steelandt, and C.
Talbot. F. B. M. personally thanks Prof. Andrew Whiten, Director of
Living Links at Edinburgh Zoo, for permission to conduct research there,
and the staff/students who kindly provided support and assistance. We
thank E. O'Sullivan for scoring monkeys' attention span, which we used
for the inter-observer reliability tests. We also thank K. Howie for
statistical advice, and the BERG (Stirling University) for insightful
comments. F. B. M gratefully acknowledges the Charles A. Lockwood
Memorial Fund and The University of Stirling for funding. F. Blake
Morton and Alexander Weiss contributed equally to writing the paper.
NR 90
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Z9 28
U1 16
U2 96
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0735-7036
EI 1939-2087
J9 J COMP PSYCHOL
JI J. Comp. Psychol.
PD AUG
PY 2013
VL 127
IS 3
BP 282
EP 298
DI 10.1037/a0031723
PG 17
WC Behavioral Sciences; Psychology; Psychology, Multidisciplinary; Zoology
SC Behavioral Sciences; Psychology; Zoology
GA 207EB
UT WOS:000323579000007
PM 23668695
ER
PT J
AU Ireland, R
Wang, R
Alinger, JB
Small, P
Bosio, CM
AF Ireland, Robin
Wang, Rong
Alinger, Joshua B.
Small, Pamela
Bosio, Catharine M.
TI Francisella tularensis SchuS4 and SchuS4 Lipids Inhibit IL-12p40 in
Primary Human Dendritic Cells by Inhibition of IRF1 and IRF8
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID LIVE VACCINE STRAIN; TRANSCRIPTION FACTOR IRF-1; P40 GENE PROMOTER;
INTERLEUKIN-12 P40; TULAREMIA; ACTIVATION; INDUCTION; INFECTION; IFN;
MACROPHAGES
AB Induction of innate immunity is essential for host survival of infection. Evasion and inhibition of innate immunity constitute a strategy used by pathogens, such as the highly virulent bacterium Francisella tularensis, to ensure their replication and transmission. The mechanism and bacterial components responsible for this suppression of innate immunity by F. tularensis are not defined. In this article, we demonstrate that lipids enriched from virulent F. tularensis strain SchuS4, but not attenuated live vaccine strain, inhibit inflammatory responses in vitro and in vivo. Suppression of inflammatory responses is associated with I kappa B alpha-independent inhibition of NF-kappa Bp65 activation and selective inhibition of activation of IFN regulatory factors. Interference with NF-kappa Bp65 and IFN regulatory factors is also observed following infection with viable SchuS4. Together these data provide novel insight into how highly virulent bacteria selectively modulate the host to interfere with innate immune responses required for survival of infection.
C1 [Ireland, Robin; Wang, Rong; Alinger, Joshua B.; Bosio, Catharine M.] NIAID, NIH, Rocky Mt Labs, Intracellular Parasites Lab,Immun Pulm Pathogens, Hamilton, MT 59840 USA.
[Small, Pamela] Univ Tennessee, Dept Microbiol, Knoxville, TN 37996 USA.
RP Bosio, CM (reprint author), NIAID, NIH, Rocky Mt Labs, Intracellular Parasites Lab,Immun Pulm Pathogens, Hamilton, MT 59840 USA.
EM bosioc@niaid.nih.gov
RI Bosio, Catharine/D-7456-2015
FU National Institutes of Health, National Institute of Allergy and
Infectious Diseases
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Allergy and
Infectious Diseases.
NR 54
TC 11
Z9 11
U1 1
U2 5
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD AUG 1
PY 2013
VL 191
IS 3
BP 1276
EP 1286
DI 10.4049/jimmunol.1300867
PG 11
WC Immunology
SC Immunology
GA 185ZJ
UT WOS:000322010100033
PM 23817430
ER
PT J
AU Kovalchik, S
Varadhan, R
AF Kovalchik, Stephanie
Varadhan, Ravi
TI Fitting Additive Binomial Regression Models with the R Package blm
SO JOURNAL OF STATISTICAL SOFTWARE
LA English
DT Article
DE constrained optimization; logistic regression; binary outcome; absolute
risk; risk difference
ID RISK DIFFERENCES; ASSOCIATION; ESTIMATORS; DESIGN; RATIOS; TESTS
AB The R package blm provides functions for fitting a family of additive regression models to binary data. The included models are the binomial linear model, in which all covariates have additive effects, and the linear-expit (lexpit) model, which allows some covariates to have additive effects and other covariates to have logisitc effects. Additive binomial regression is a model of event probability, and the coefficients of linear terms estimate covariate-adjusted risk differences. Thus, in contrast to logistic regression, additive binomial regression puts focus on absolute risk and risk differences. In this paper, we give an overview of the methodology we have developed to fit the binomial linear and lexpit models to binary outcomes from cohort and population-based case-control studies. We illustrate the blm package's methods for additive model estimation, diagnostics, and inference with risk association analyses of a bladder cancer nested case-control study in the NIH-AARP Diet and Health Study.
C1 [Kovalchik, Stephanie] NCI, Div Canc Epidemiol & Genet, Biostat Branch, Rockville, MD 20852 USA.
[Varadhan, Ravi] Johns Hopkins Univ, Baltimore, MD 21218 USA.
RP Kovalchik, S (reprint author), NCI, Div Canc Epidemiol & Genet, Biostat Branch, Rockville, MD 20852 USA.
EM kovalchiksa@mail.nih.gov
FU NIH/NCI
FX This research was supported by the intramural research program of the
NIH/NCI. We thank Dr. Hormuzd A. Katki and Dr. Sholom Wacholder for
their input on this work. We are grateful to the participants of the
NIH-AARP Diet and Health Study. Dr. Ravi Varadhan is a Brook dale
Leadership in Aging Fellow at the Johns Hopkins University.
NR 25
TC 1
Z9 1
U1 1
U2 6
PU JOURNAL STATISTICAL SOFTWARE
PI LOS ANGELES
PA UCLA DEPT STATISTICS, 8130 MATH SCIENCES BLDG, BOX 951554, LOS ANGELES,
CA 90095-1554 USA
SN 1548-7660
J9 J STAT SOFTW
JI J. Stat. Softw.
PD AUG
PY 2013
VL 54
IS 1
BP 1
EP 18
PG 18
WC Computer Science, Interdisciplinary Applications; Statistics &
Probability
SC Computer Science; Mathematics
GA 211LO
UT WOS:000323909300001
ER
PT J
AU Sieh, W
Koebel, M
Longacre, TA
Bowtell, DD
Defazio, A
Goodman, MT
Hogdall, E
Deen, S
Wentzensen, N
Moysich, KB
Brenton, JD
Clarke, BA
Menon, U
Gilks, CB
Kim, A
Madore, J
Fereday, S
George, J
Galletta, L
Lurie, G
Wilkens, LR
Carney, ME
Thompson, PJ
Matsuno, RK
Kjaer, SK
Jensen, A
Hogdall, C
Kalli, KR
Fridley, BL
Keeney, GL
Vierkant, RA
Cunningham, JM
Brinton, LA
Yang, HP
Sherman, ME
Garcia-Closas, M
Lissowska, J
Odunsi, K
Morrison, C
Lele, S
Bshara, W
Sucheston, L
Jimenez-Linan, M
Driver, K
Alsop, J
Mack, M
McGuire, V
Rothstein, JH
Rosen, BP
Bernardini, MQ
Mackay, H
Oza, A
Wozniak, EL
Benjamin, E
Gentry-Maharaj, A
Gayther, SA
Tinker, AV
Prentice, LM
Chow, C
Anglesio, MS
Johnatty, SE
Chenevix-Trench, G
Whittemore, AS
Pharoah, PDP
Goode, EL
Huntsman, DG
Ramus, SJ
AF Sieh, Weiva
Koebel, Martin
Longacre, Teri A.
Bowtell, David D.
defazio, Anna
Goodman, Marc T.
Hogdall, Estrid
Deen, Suha
Wentzensen, Nicolas
Moysich, Kirsten B.
Brenton, James D.
Clarke, Blaise A.
Menon, Usha
Gilks, C. Blake
Kim, Andre
Madore, Jason
Fereday, Sian
George, Joshy
Galletta, Laura
Lurie, Galina
Wilkens, Lynne R.
Carney, Michael E.
Thompson, Pamela J.
Matsuno, Rayna K.
Kjaer, Susanne Krueger
Jensen, Allan
Hogdall, Claus
Kalli, Kimberly R.
Fridley, Brooke L.
Keeney, Gary L.
Vierkant, Robert A.
Cunningham, Julie M.
Brinton, Louise A.
Yang, Hannah P.
Sherman, Mark E.
Garcia-Closas, Montserrat
Lissowska, Jolanta
Odunsi, Kunle
Morrison, Carl
Lele, Shashikant
Bshara, Wiam
Sucheston, Lara
Jimenez-Linan, Mercedes
Driver, Kristy
Alsop, Jennifer
Mack, Marie
McGuire, Valerie
Rothstein, Joseph H.
Rosen, Barry P.
Bernardini, Marcus Q.
Mackay, Helen
Oza, Amit
Wozniak, Eva L.
Benjamin, Elizabeth
Gentry-Maharaj, Aleksandra
Gayther, Simon A.
Tinker, Anna V.
Prentice, Leah M.
Chow, Christine
Anglesio, Michael S.
Johnatty, Sharon E.
Chenevix-Trench, Georgia
Whittemore, Alice S.
Pharoah, Paul D. P.
Goode, Ellen L.
Huntsman, David G.
Ramus, Susan J.
TI Hormone-receptor expression and ovarian cancer survival: an Ovarian
Tumor Tissue Analysis consortium study
SO LANCET ONCOLOGY
LA English
DT Article
ID PARAFFIN-EMBEDDED TISSUE; 1 MESSENGER-RNA; PROGESTERONE-RECEPTOR;
ESTROGEN-RECEPTOR; EPITHELIAL OVARIAN; BREAST-CANCER; FAVORABLE
PROGNOSIS; SEROUS CARCINOMA; GROWTH-FACTOR; CELL-TYPE
AB Background Few biomarkers of ovarian cancer prognosis have been established, partly because subtype-specific associations might be obscured in studies combining all histopathological subtypes. We examined whether tumour expression of the progesterone receptor (PR) and oestrogen receptor (ER) was associated with subtype-specific survival.
Methods 12 studies participating in the Ovarian Tumor Tissue Analysis consortium contributed tissue microarray sections and clinical data to our study. Participants included in our analysis had been diagnosed with invasive serous, mucinous, endometrioid, or clear-cell carcinomas of the ovary. For a patient to be eligible, tissue microarrays, clinical follow-up data, age at diagnosis, and tumour grade and stage had to be available. Clinical data were obtained from medical records, cancer registries, death certificates, pathology reports, and review of histological slides. PR and ER statuses were assessed by central immunohistochemistry analysis done by masked pathologists. PR and ER staining was defined as negative (<1% tumour cell nuclei), weak (1 to <50%), or strong (>= 50%). Associations with disease-specific survival were assessed.
Findings 2933 women with invasive epithelial ovarian cancer were included: 1742 with high-grade serous carcinoma, 110 with low-grade serous carcinoma, 207 with mucinous carcinoma, 484 with endometrioid carcinoma, and 390 with clear-cell carcinoma. PR expression was associated with improved disease-specific survival in endometrioid carcinoma (log-rank p<0.0001) and high-grade serous carcinoma (log-rank p=0.0006), and ER expression was associated with improved disease-specific survival in endometrioid carcinoma (log-rank p<0.0001). We recorded no significant associations for mucinous, clear-cell, or low-grade serous carcinoma. Positive hormone-receptor expression (weak or strong staining for PR or ER, or both) was associated with significantly improved disease-specific survival in endometrioid carcinoma compared with negative hormone-receptor expression, independent of study site, age, stage, and grade (hazard ratio 0.33, 95% CI 0.21-0.51; p<0.0001). Strong PR expression was independently associated with improved disease-specific survival in high-grade serous carcinoma (0.71,0.55-0.91; p=0.0080), but weak PR expression was not (1.02, 0.89-1.18; p=0.74).
Interpretation PR and ER are prognostic biomarkers for endometrioid and high-grade serous ovarian cancers. Clinical trials, stratified by subtype and biomarker status, are needed to establish whether hormone-receptor status predicts response to endocrine treatment, and whether it could guide personalised treatment for ovarian cancer.
C1 [Longacre, Teri A.] Stanford Univ, Div Epidemiol, Dept Hlth Res & Policy, Stanford, CA 94305 USA.
[Koebel, Martin] Univ Calgary, Dept Pathol & Lab Med, Calgary, AB T2N 2T9, Canada.
[Bowtell, David D.; Fereday, Sian; George, Joshy; Galletta, Laura] Peter MacCallum Canc Inst, East Melbourne, Vic, Australia.
[Bowtell, David D.] Univ Melbourne, Dept Biochem & Mol Biol, Melbourne, Vic, Australia.
[Bowtell, David D.] Univ Melbourne, Sir Peter MacCullum Dept Oncol, Melbourne, Vic, Australia.
[defazio, Anna] Univ Sydney, Dept Gynaecol Oncol, Westmead, NSW 2145, Australia.
[defazio, Anna] Univ Sydney, Westmead Inst Canc Res, Westmead, NSW 2145, Australia.
[Goodman, Marc T.; Thompson, Pamela J.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA.
[Hogdall, Estrid; Kjaer, Susanne Krueger; Jensen, Allan] Danish Canc Soc Res Ctr, Virus Lifestyle & Genes Unit, Copenhagen, Denmark.
[Hogdall, Estrid] Univ Copenhagen, Dept Pathol, Herlev Hosp, Copenhagen, Denmark.
[Deen, Suha] Nottingham Univ Hosp NHS Trust, Queens Med Ctr, Dept Histopathol, Nottingham, England.
[Wentzensen, Nicolas; Brinton, Louise A.; Yang, Hannah P.; Sherman, Mark E.] Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD USA.
[Moysich, Kirsten B.; Lele, Shashikant; Sucheston, Lara] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA.
[Odunsi, Kunle] Roswell Pk Canc Inst, Dept Gynecol Oncol, Buffalo, NY 14263 USA.
[Morrison, Carl; Bshara, Wiam] Roswell Pk Canc Inst, Dept Pathol & Lab Med, Buffalo, NY 14263 USA.
[Brenton, James D.] Univ Cambridge, Canc Res UK Cambridge Inst, Cambridge, England.
[Brenton, James D.; Driver, Kristy; Alsop, Jennifer; Mack, Marie; Pharoah, Paul D. P.] Univ Cambridge, Dept Oncol, Cambridge, England.
[Jimenez-Linan, Mercedes] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England.
[Pharoah, Paul D. P.] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
[Brenton, James D.; Jimenez-Linan, Mercedes] Cambridge Univ Hosp, Addenbrookes Hosp, NHS Fdn Trust, Cambridge, England.
[Brenton, James D.; Jimenez-Linan, Mercedes] Natl Inst Hlth, Res Cambridge Biomed Res Ctr, Cambridge, England.
[Clarke, Blaise A.] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada.
[Rosen, Barry P.; Bernardini, Marcus Q.; Oza, Amit] Univ Toronto, Dept Obstet & Gynecol, Toronto, ON, Canada.
[Mackay, Helen] Univ Toronto, Div Med Oncol, Dept Med, Toronto, ON, Canada.
[Menon, Usha; Wozniak, Eva L.; Gentry-Maharaj, Aleksandra] UCL, Gynaecol Canc Res Ctr, Elizabeth Garrett Anderson Inst Womens Hlth, London, England.
[Gilks, C. Blake; Anglesio, Michael S.] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada.
[Gilks, C. Blake] Univ British Columbia, Genet Pathol Evaluat Ctr, Vancouver, BC V5Z 1M9, Canada.
[Gilks, C. Blake] Univ British Columbia, Vancouver Gen Hosp, Vancouver, BC V5Z 1M9, Canada.
[Kim, Andre; Gayther, Simon A.; Ramus, Susan J.] Univ So Calif, Dept Prevent Med, Keck Sch Med, Ctr Comprehens Canc, Los Angeles, CA 90089 USA.
[Madore, Jason; Prentice, Leah M.; Huntsman, David G.] British Columbia Canc Agcy, Ctr Translat & Appl Genom, Vancouver, BC V5Z 4E6, Canada.
[Tinker, Anna V.] British Columbia Canc Agcy, Dept Med Oncol, Vancouver, BC V5Z 4E6, Canada.
[Lurie, Galina; Wilkens, Lynne R.; Carney, Michael E.; Matsuno, Rayna K.] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
[Kjaer, Susanne Krueger; Hogdall, Claus] Rigshosp, Juliane Marie Ctr, Dept Obstet & Gynecol, DK-2100 Copenhagen, Denmark.
[Kalli, Kimberly R.] Mayo Clin, Dept Med Oncol, Rochester, MN USA.
[Keeney, Gary L.] Mayo Clin, Div Anat Pathol, Rochester, MN USA.
[Cunningham, Julie M.] Mayo Clin, Div Expt Pathol, Rochester, MN USA.
[Vierkant, Robert A.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
[Vierkant, Robert A.] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN USA.
Mayo Clin, Div Epidemiol, Dept Hlth Sci Res, Rochester, MN USA.
[Fridley, Brooke L.] Univ Kansas, Med Ctr, Dept Biostat, Kansas City, KS 66103 USA.
[Garcia-Closas, Montserrat] Inst Canc Res, London SW3 6JB, England.
[Lissowska, Jolanta] Mem Canc Ctr, Warsaw, Poland.
[Lissowska, Jolanta] Inst Oncol, Warsaw, Poland.
[Benjamin, Elizabeth] UCL, Inst Canc, Dept Pathol, London, England.
[Johnatty, Sharon E.; Chenevix-Trench, Georgia] Queensland Inst Med Res, Dept Genet, Brisbane, Qld 4006, Australia.
RP Koebel, M (reprint author), Univ Calgary, Dept Pathol & Lab Med, 1403 29th St NW, Calgary, AB T2N 2T9, Canada.
EM martin.koebel@cls.ab.ca
RI Whittemore, Alice/F-9925-2014; deFazio, Anna/D-3939-2013; Fridley,
Brooke/D-8315-2015; Garcia-Closas, Montserrat /F-3871-2015; Brinton,
Louise/G-7486-2015; Bowtell, David/H-1007-2016; Johnatty,
Sharon/R-8890-2016;
OI Kobel, Martin/0000-0002-6615-2037; Ramus, Susan/0000-0003-0005-7798;
Lissowska, Jolanta/0000-0003-2695-5799; deFazio,
Anna/0000-0003-0057-4744; Fridley, Brooke/0000-0001-7739-7956;
Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton,
Louise/0000-0003-3853-8562; Bowtell, David/0000-0001-9089-7525;
Johnatty, Sharon/0000-0002-7888-1966; Anglesio,
Michael/0000-0003-1639-5003; Kjaer, Susanne/0000-0002-8347-1398;
Brenton, James/0000-0002-5738-6683
FU Carraresi Foundation; University of British Columbia Hospital
Foundation; US Department of Defense [DAMD17-01-1-0729]; Cancer Council
Victoria; Queensland Cancer Fund; Cancer Council New South Wales; Cancer
Council South Australia; Cancer Foundation of Western Australia; Cancer
Council Tasmania; Australian National Health and Medical Research
Council [400413, 400281]; US National Institutes of Health (NIH)
[R01CA58598, N01CN55424, N01PC67001]; NIH [R01CA61107, R01CA122443,
P50CA136393, Z01CP010126, U01CA71966, U01CA69417, R01CA16056,
K07CA143047]; Danish Cancer Society [94 222 52]; Mermaid I project; Mayo
Foundation; Fred C and Katherine B Andersen Foundation; Roswell Park
Cancer Institute Alliance Foundation; Cancer Research UK [C490/A10119,
C490/A10124]; National Institute for Health Research (NIHR) Cambridge
Biomedical Research Centre; Cambridge Experimental Cancer Medicine
Centre; Eve Appeal (Oak Foundation); NIHR University College London
Hospitals Biomedical Research Centre; British Columbia Cancer
Foundation; Vancouver General Hospital and University of British
Columbia Hospital Foundation; Sanofi-Aventis Canada
FX This study was supported by the Carraresi Foundation through donations
to the Vancouver General Hospital and University of British Columbia
Hospital Foundation. AOC was supported by the US Department of Defense
(DAMD17-01-1-0729), Cancer Council Victoria, Queensland Cancer Fund,
Cancer Council New South Wales, Cancer Council South Australia, Cancer
Foundation of Western Australia, Cancer Council Tasmania, Australian
National Health and Medical Research Council (grants 400413 and 400281).
HAW was funded by the US National Institutes of Health (NIH; grants
R01CA58598, N01CN55424, N01PC67001). MAL was funded by the NIH
(R01CA61107), Danish Cancer Society (94 222 52), and the Mermaid I
project. MAY+MAC was funded by the NIH (grants R01CA122443 and
P50CA136393), Mayo Foundation, and the Fred C and Katherine B Andersen
Foundation. The Polish Ovarian Cancer Study (POL) was funded by the NIH
(Z01CP010126). The Roswell Park Cancer Institute Ovarian Cancer Cohort
(RPX) was funded by the Roswell Park Cancer Institute Alliance
Foundation. The Study of Epidemiology and Risk Factors in Cancer
Heredity (SEA) was funded by Cancer Research UK (C490/A10119
C490/A10124), National Institute for Health Research (NIHR) Cambridge
Biomedical Research Centre, and the Cambridge Experimental Cancer
Medicine Centre. STA was funded by the NIH (U01CA71966, U01CA69417,
R01CA16056, and K07CA143047). The UK Ovarian Cancer Population Study
(UKO) was funded by Eve Appeal (Oak Foundation) and was supported by
researchers at the NIHR University College London Hospitals Biomedical
Research Centre. VAN was funded by the British Columbia Cancer
Foundation, Vancouver General Hospital and University of British
Columbia Hospital Foundation, and Sanofi-Aventis Canada. We thank all
the women, study centres, and personnel who participated in this study.
We gratefully acknowledge the contributions of the Australian Ovarian
Cancer Study Group; Karin Goodman, Ashley Pitzer, and the Mayo Clinic
Medical Genome Facility; Fiona Blows and the SEARCH team; Ian Jacobs,
Andy Ryan, Jeremy Ford, Nayaladzi Balogun; and the Cheryl Brown Ovarian
Cancer Outcomes Unit.
NR 50
TC 80
Z9 83
U1 2
U2 25
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
EI 1474-5488
J9 LANCET ONCOL
JI Lancet Oncol.
PD AUG
PY 2013
VL 14
IS 9
BP 853
EP 862
DI 10.1016/S1470-2045(13)70253-5
PG 10
WC Oncology
SC Oncology
GA 205DZ
UT WOS:000323423400042
PM 23845225
ER
PT J
AU Naranjo-Suarez, S
Carlson, BA
Tobe, R
Yoo, MH
Tsuji, PA
Gladyshev, VN
Hatfield, DL
AF Naranjo-Suarez, Salvador
Carlson, Bradley A.
Tobe, Ryuta
Yoo, Min-Hyuk
Tsuji, Petra A.
Gladyshev, Vadim N.
Hatfield, Dolph L.
TI Regulation of HIF-1 alpha activity by overexpression of thioredoxin is
independent of thioredoxin reductase status
SO MOLECULES AND CELLS
LA English
DT Article
DE HIF-1 alpha stability; HIF transcriptional activity; thioredoxin 1;
thioredoxin reductase 1
ID HYPOXIA-INDUCIBLE FACTOR; MITOCHONDRIAL RESPIRATORY-CHAIN; ENDOTHELIAL
GROWTH-FACTOR; LOW-OXYGEN TENSION; NF-KAPPA-B; FACTOR 1-ALPHA;
HIF-ALPHA; TRANSCRIPTIONAL ACTIVITY; FACTOR-1-ALPHA PROTEIN; PROLYL
HYDROXYLATION
AB Under hypoxic conditions, cells activate a transcriptional response mainly driven by hypoxia-inducible factors (HIFs). HIF-1 alpha stabilization and activity are known to be regulated by thioredoxin 1 (Txn1), but how the thioredoxin system regulates the hypoxic response is unknown. By examining the effects of Txn1 overexpression on HIF-1 alpha function in HeLa, HT-29, MCF-7 and EMT6 cell lines, we found that this oxidoreductase did not stabilize HIF-1 alpha, yet could increase its activity. These effects were dependent on the redox function of Txn1. However, Txn1 deficiency did not affect HIF-1 alpha hypoxic-stabilization and activity, and overexpression of thioredoxin reductase 1 (TR1), the natural Txn1 reductase, had no influence on HIF-1 alpha activity. Moreover, overexpression of Txn1 in TR1 deficient HeLa and EMT6 cells was still able to increase HIF-1 alpha hypoxic activity. These results indicate that Txn1 is not essential for HIF-1 alpha hypoxic stabilization or activity, that its overexpression can increase HIF-1 alpha hypoxic activity, and that this effect is observed regardless of TR1 status. Thus, regulation of HIF-1 alpha by the thioredoxin system depends on the specific levels of this system's major components.
C1 [Naranjo-Suarez, Salvador; Carlson, Bradley A.; Tobe, Ryuta; Yoo, Min-Hyuk; Hatfield, Dolph L.] NIH, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res, Bethesda, MD 20892 USA.
[Tsuji, Petra A.] Towson Univ, Dept Biol Sci, Towson, MD 21252 USA.
[Gladyshev, Vadim N.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA.
[Gladyshev, Vadim N.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
RP Hatfield, DL (reprint author), NIH, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA.
EM hatfield@mail.nih.gov
FU National Institutes of Health, NCI, Center for Cancer Research; NIH;
National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, NCI, Center for Cancer Research to D. L.
H., NIH grants to V.N.G. and the National Cancer Institute, National
Institutes of Health, under Contract No. HHSN261200800001E.
NR 40
TC 4
Z9 4
U1 0
U2 8
PU KOREAN SOC MOLECULAR & CELLULAR BIOLOGY
PI SEOUL
PA 635-4, YUCKSAM-DONG, GANGNAM-GU, SEOUL 135-703, SOUTH KOREA
SN 1016-8478
J9 MOL CELLS
JI Mol. Cells
PD AUG
PY 2013
VL 36
IS 2
BP 151
EP 157
DI 10.1007/s10059-013-0121-y
PG 7
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 206FN
UT WOS:000323504200008
PM 23912593
ER
PT J
AU Gremel, CM
Costa, RM
AF Gremel, Christina M.
Costa, Rui M.
TI Orbitofrontal and striatal circuits dynamically encode the shift between
goal-directed and habitual actions
SO NATURE COMMUNICATIONS
LA English
DT Article
ID OBSESSIVE-COMPULSIVE DISORDER; ORBITAL PREFRONTAL CORTEX; REINFORCER
DEVALUATION; BASOLATERAL AMYGDALA; DECISION-MAKING; DORSAL STRIATUM;
DOUBLE DISSOCIATION; DISTINCT ROLES; REWARD VALUE; BRAIN
AB Shifting between goal-directed and habitual actions allows for efficient and flexible decision making. Here we demonstrate a novel, within-subject instrumental lever-pressing paradigm, in which mice shift between goal-directed and habitual actions. We identify a role for orbitofrontal cortex (OFC) in actions following outcome revaluation, and confirm that dorsal medial (DMS) and lateral striatum (DLS) mediate different action strategies. Simultaneous in vivo recordings of OFC, DMS and DLS neuronal ensembles during shifting reveal that the same neurons display different activities depending on whether presses are goal-directed or habitual, with DMS and OFC becoming more and DLS less engaged during goal-directed actions. Importantly, the magnitude of neural activity changes in OFC following changes in outcome value positively correlates with the level of goal-directed behavior. Chemogenetic inhibition of OFC disrupts goal-directed actions, whereas optogenetic activation of OFC specifically increases goal-directed pressing. These results also reveal a role for OFC in action revaluation, which has implications for understanding compulsive behavior.
C1 [Gremel, Christina M.; Costa, Rui M.] NIAAA, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA.
[Costa, Rui M.] Champalimaud Inst Unknown, Champalimaud Neurosci Programme, P-1400038 Lisbon, Portugal.
RP Gremel, CM (reprint author), NIAAA, Lab Integrat Neurosci, NIH, TS-20,5625 Fishers Lane, Bethesda, MD 20892 USA.
EM gremelc@mail.nih.gov; ruicosta@fchampalimaud.org
OI Costa, Rui/0000-0003-0495-8374
FU NIAAA Division of Intramural Clinical and Biological Research; European
Research Council [243393]; HHMI International Early Career Scientist
Grant
FX We thank David Lovinger, Eduardo Dias-Ferreira, Xin Jin and Nicholas
Oesch for comments on the manuscript. The DREADD virus was provided by
the University of North Carolina Vector Core and Dr. R. Jude Samulski.
This research was supported by the NIAAA Division of Intramural Clinical
and Biological Research and the European Research Council Grant (243393)
and HHMI International Early Career Scientist Grant to R.M.C.
NR 56
TC 78
Z9 80
U1 3
U2 30
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 AUG
PY 2013
VL 4
AR 2264
DI 10.1038/ncomms3264
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 209JG
UT WOS:000323751200004
PM 23921250
ER
PT J
AU Lin, L
Sun, W
Throesch, B
Kung, F
Decoster, JT
Berner, CJ
Cheney, RE
Rudy, B
Hoffman, DA
AF Lin, Lin
Sun, Wei
Throesch, Ben
Kung, Faith
Decoster, Jameice T.
Berner, Cory J.
Cheney, Richard E.
Rudy, Bernardo
Hoffman, Dax A.
TI DPP6 regulation of dendritic morphogenesis impacts hippocampal synaptic
development
SO NATURE COMMUNICATIONS
LA English
DT Article
ID CA1 PYRAMIDAL NEURONS; MYOSIN-X; PROTEIN DPPX; POTASSIUM CHANNELS; K+
CURRENT; KV4.2; MOTOR; CD26; IV; EXCITABILITY
AB Dipeptidyl-peptidase 6 is an auxiliary subunit of Kv4-mediated A-type K+ channels that, in addition to enhancing channel surface expression, potently accelerates their kinetics. The dipeptidyl-peptidase 6 gene has been associated with a number of human central nervous system disorders including autism spectrum disorders and schizophrenia. Here we employ knockdown and genetic deletion of dipeptidyl-peptidase 6 to reveal its importance for the formation and stability of dendritic filopodia during early neuronal development. We find that the hippocampal neurons lacking dipeptidyl-peptidase 6 show a sparser dendritic branching pattern along with fewer spines throughout development and into adulthood. In electrophysiological and imaging experiments, we show that these deficits lead to fewer functional synapses and occur independently of the potassium channel subunit Kv4.2. We report that dipeptidyl-peptidase 6 interacts with a filopodia-associated myosin as well as with fibronectin in the extracellular matrix. dipeptidyl-peptidase 6 therefore has an unexpected but important role in cell adhesion and motility, impacting the hippocampal synaptic development and function.
C1 [Lin, Lin; Sun, Wei; Throesch, Ben; Kung, Faith; Decoster, Jameice T.; Berner, Cory J.; Hoffman, Dax A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Neurophysiol & Biophys Sect, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
[Sun, Wei] Peking Univ, Hlth Sci Ctr, Neurosci Res Inst & Dept Neurobiol, Beijing 100083, Peoples R China.
[Cheney, Richard E.] Univ N Carolina, Dept Cell & Mol Physiol, Chapel Hill, NC 27599 USA.
[Rudy, Bernardo] NYU, Sch Med, Dept Physiol & Neurosci, New York, NY 10016 USA.
[Rudy, Bernardo] NYU, Sch Med, Smilow Neurosci Program, New York, NY 10016 USA.
RP Hoffman, DA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Neurophysiol & Biophys Sect, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
EM hoffmand@mail.nih.gov
RI Hoffman, Dax/E-5155-2011;
OI Hoffman, Dax/0000-0001-6999-2157; Throesch,
Benjamin/0000-0001-6834-8263; Rudy, Bernardo/0000-0001-5748-6900
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development; NIH [NS045217,
R01DC03299]
FX This work was supported by the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human Development
along with NIH grants NS045217 to BR and R01DC03299 to REC. We thank
Vincent Schram in the NICHD Microscopy & Imaging Core for technical
assistance.
NR 39
TC 11
Z9 11
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD AUG
PY 2013
VL 4
AR 2270
DI 10.1038/ncomms3270
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 209JG
UT WOS:000323751200010
PM 23912628
ER
PT J
AU Srinivasan, P
Yasgar, A
Luci, DK
Beatty, WL
Hu, X
Andersen, J
Narum, DL
Moch, JK
Sun, HM
Haynes, JD
Maloney, DJ
Jadhav, A
Simeonov, A
Miller, LH
AF Srinivasan, Prakash
Yasgar, Adam
Luci, Diane K.
Beatty, Wandy L.
Hu, Xin
Andersen, John
Narum, David L.
Moch, J. Kathleen
Sun, Hongmao
Haynes, J. David
Maloney, David J.
Jadhav, Ajit
Simeonov, Anton
Miller, Louis H.
TI Disrupting malaria parasite AMA1-RON2 interaction with a small molecule
prevents erythrocyte invasion
SO NATURE COMMUNICATIONS
LA English
DT Article
ID APICAL MEMBRANE ANTIGEN-1; PLASMODIUM-FALCIPARUM; PROTEIN-INTERACTION;
HOT-SPOTS; AMA1; RESISTANCE; INHIBITORS; BINDING; POTENT; P53
AB Plasmodium falciparum resistance to artemisinin derivatives, the first-line antimalarial drug, drives the search for new classes of chemotherapeutic agents. Current discovery is primarily directed against the intracellular forms of the parasite. However, late schizont-infected red blood cells (RBCs) may still rupture and cause disease by sequestration; consequently targeting invasion may reduce disease severity. Merozoite invasion of RBCs requires interaction between two parasite proteins AMA1 and RON2. Here we identify the first inhibitor of this interaction that also blocks merozoite invasion in genetically distinct parasites by screening a library of over 21,000 compounds. We demonstrate that this inhibition is mediated by the small molecule binding to AMA1 and blocking the formation of AMA1-RON complex. Electron microscopy confirms that the inhibitor prevents junction formation, a critical step in invasion that results from AMA1-RON2 binding. This study uncovers a strategy that will allow for highly effective combination therapies alongside existing antimalarial drugs.
C1 [Srinivasan, Prakash; Andersen, John; Miller, Louis H.] NIAID, Lab Malaria & Vector Res, Div Intramural Res, NIH, Bethesda, MD 20852 USA.
[Yasgar, Adam; Luci, Diane K.; Hu, Xin; Sun, Hongmao; Maloney, David J.; Jadhav, Ajit; Simeonov, Anton] NIH, Natl Ctr Advancing Translat Sci, Bethesda, MD 20850 USA.
[Beatty, Wandy L.] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63130 USA.
[Narum, David L.] NIAID, Lab Malaria Immunol & Vaccinol, Div Intramural Res, NIH, Bethesda, MD 20852 USA.
[Moch, J. Kathleen; Haynes, J. David] Walter Reed Army Inst Res, Div Malaria Vaccine Dev, Silver Spring, MD 20910 USA.
RP Srinivasan, P (reprint author), NIAID, Lab Malaria & Vector Res, Div Intramural Res, NIH, Bethesda, MD 20852 USA.
EM srinivasanp@niaid.nih.gov
FU Division of Intramural Research, NIAID, NIH; Molecular Libraries
Program, NIH Common Fund
FX This study was supported in part by the Division of Intramural Research,
NIAID, NIH and by the Molecular Libraries Program, NIH Common Fund. We
thank Dr. Jason Regules for providing the FVO parasite, Dr. Susan Pierce
for critical reading and suggestions on the manuscript. We thank Wendy
Lea, Sam Michael, Paul Shinn, Danielle van Leer and Michael Balcom for
their help with the binding assays, online robotic screen and compound
management.
NR 40
TC 35
Z9 35
U1 0
U2 20
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 AUG
PY 2013
VL 4
AR 2261
DI 10.1038/ncomms3261
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 209JG
UT WOS:000323751200001
PM 23907321
ER
PT J
AU Zhao, ZH
Zhou, ZJ
Bao, JF
Wang, ZY
Hu, J
Chi, XQ
Ni, KY
Wang, RF
Chen, XY
Chen, Z
Gao, JH
AF Zhao, Zhenghuan
Zhou, Zijian
Bao, Jianfeng
Wang, Zhenyu
Hu, Juan
Chi, Xiaoqin
Ni, Kaiyuan
Wang, Ruifang
Chen, Xiaoyuan
Chen, Zhong
Gao, Jinhao
TI Octapod iron oxide nanoparticles as high-performance T-2 contrast agents
for magnetic resonance imaging
SO NATURE COMMUNICATIONS
LA English
DT Article
ID HIGH-INDEX FACETS; PLATINUM NANOCRYSTALS; PROSTATE-CANCER; MRI;
PARTICLES; SIZE
AB Spherical superparamagnetic iron oxide nanoparticles have been developed as T-2-negative contrast agents for magnetic resonance imaging in clinical use because of their biocompatibility and ease of synthesis; however, they exhibit relatively low transverse relaxivity. Here we report a new strategy to achieve high transverse relaxivity by controlling the morphology of iron oxide nanoparticles. We successfully fabricate size-controllable octapod iron oxide nanoparticles by introducing chloride anions. The octapod iron oxide nanoparticles (edge length of 30 nm) exhibit an ultrahigh transverse relaxivity value (679.3 +/- 30 mM(-1)s(-1)), indicating that these octapod iron oxide nanoparticles are much more effective T-2 contrast agents for in vivo imaging and small tumour detection in comparison with conventional iron oxide nanoparticles, which holds great promise for highly sensitive, early stage and accurate detection of cancer in the clinic.
C1 [Zhao, Zhenghuan; Zhou, Zijian; Hu, Juan; Ni, Kaiyuan; Gao, Jinhao] Xiamen Univ, Coll Chem & Chem Engn, Key Lab Chem Biol Fujian Prov, State Key Lab Phys Chem Solid Surfaces, Xiamen 361005, Peoples R China.
[Zhao, Zhenghuan; Zhou, Zijian; Hu, Juan; Ni, Kaiyuan; Gao, Jinhao] Xiamen Univ, Coll Chem & Chem Engn, Dept Biol Chem, Xiamen 361005, Peoples R China.
[Bao, Jianfeng; Wang, Zhenyu; Wang, Ruifang; Chen, Zhong] Xiamen Univ, Fujian Key Lab Plasma & Magnet Resonance, Dept Phys & Elect Sci, Xiamen 361005, Peoples R China.
[Chi, Xiaoqin] Xiamen Univ, Zhongshan Hosp, Fujian Prov Key Lab Chron Liver Dis & Hepatocellu, Xiamen 361004, Peoples R China.
[Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
[Gao, Jinhao] Xiamen Univ, Sch Publ Hlth, Ctr Mol Imaging & Translat Med, Xiamen 361005, Peoples R China.
RP Gao, JH (reprint author), Xiamen Univ, Coll Chem & Chem Engn, Key Lab Chem Biol Fujian Prov, State Key Lab Phys Chem Solid Surfaces, Xiamen 361005, Peoples R China.
EM jhgao@xmu.edu.cn
RI Gao, Jinhao/F-5092-2010; wang, ruifang/D-3037-2016; Ni,
Kaiyuan/B-3569-2016; Chen, Zhong/G-4601-2010
OI Gao, Jinhao/0000-0003-3215-7013; wang, ruifang/0000-0002-8456-9776; Ni,
Kaiyuan/0000-0002-8152-6746;
FU National Key Basic Research Program of China [2013CB933901,
2013CB733802]; National Natural Science Foundation of China [21222106,
21021061, 81000662, 81201805, J1210014]; Natural Science Foundation of
Fujian [2013J06005]; Program for New Century Excellent Talents in
University [NCET-10-0709]
FX This work was supported by the National Key Basic Research Program of
China (2013CB933901 and 2013CB733802), National Natural Science
Foundation of China (21222106, 21021061, 81000662, 81201805 and
J1210014), Natural Science Foundation of Fujian (2013J06005) and the
Program for New Century Excellent Talents in University (NCET-10-0709).
We thank B. Xu, L.S. Zheng, E. Meggers and C.B. Cai for the fruitful
discussions.
NR 42
TC 78
Z9 80
U1 17
U2 207
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 AUG
PY 2013
VL 4
AR 2266
DI 10.1038/ncomms3266
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 209JG
UT WOS:000323751200006
PM 23903002
ER
PT J
AU Mensah, GA
AF Mensah, George A.
TI PUBLIC HEALTH Cardiovascular disease insights-something new out of
Africa
SO NATURE REVIEWS CARDIOLOGY
LA English
DT Editorial Material
C1 NIH, Natl Heart Lung & Blood Inst, Bethesda, MD 20892 USA.
RP Mensah, GA (reprint author), NIH, Natl Heart Lung & Blood Inst, 31 Ctr Dr,MSC 2486, Bethesda, MD 20892 USA.
EM george.mensah@nih.gov
OI Mensah, George/0000-0002-0387-5326
NR 10
TC 1
Z9 1
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-5002
J9 NAT REV CARDIOL
JI Nat. Rev. Cardiol.
PD AUG
PY 2013
VL 10
IS 8
BP 433
EP 434
DI 10.1038/nrcardio.2013.96
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 187KY
UT WOS:000322118800001
PM 23817189
ER
PT J
AU Kehn, ME
Ho, PS
Kroll, T
AF Kehn, M. E.
Ho, P. -S.
Kroll, T.
TI Identifying the health service needs of homeless adults with physical
disabilities
SO PUBLIC HEALTH
LA English
DT Article
C1 [Kehn, M. E.] Math Policy Res, Washington, DC USA.
[Ho, P. -S.] NIH Clin Ctr, Hlth Serv Res, Bethesda, MD USA.
[Kroll, T.] Univ Dundee, Social Dimens Hlth Inst, Dundee DD1 4HJ, Scotland.
[Kroll, T.] Univ St Andrews, Social Dimens Hlth Inst, Dundee DD1 4HJ, Scotland.
RP Kroll, T (reprint author), Univ Dundee, Social Dimens Hlth Inst, 11 Airlie Pl, Dundee DD1 4HJ, Scotland.
EM t.kroll@dundee.ac.uk
FU Agency for Healthcare Research and Quality [1R03HS013977-01A1]
FX This study was supported by the Agency for Healthcare Research and
Quality, Grant No. 1R03HS013977-01A1 and conducted by the authors at the
National Rehabilitation Hospital, Research Division, Washington, DC.
NR 9
TC 0
Z9 0
U1 0
U2 0
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 0033-3506
J9 PUBLIC HEALTH
JI Public Health
PD AUG
PY 2013
VL 127
IS 8
BP 785
EP 787
DI 10.1016/j.puhe.2013.01.011
PG 3
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 207LF
UT WOS:000323599700014
PM 23876299
ER
PT J
AU Bryant, BJ
Yau, YY
Arceo, SM
Hopkins, JA
Leitman, SF
AF Bryant, Barbara J.
Yau, Yu Ying
Arceo, Sarah M.
Hopkins, Julie A.
Leitman, Susan F.
TI Ascertainment of iron deficiency and depletion in blood donors through
screening questions for pica and restless legs syndrome
SO TRANSFUSION
LA English
DT Article
ID PERIODIC LIMB MOVEMENTS; GASTRIC BYPASS-SURGERY; ANEMIA; PAGOPHAGIA;
MANAGEMENT; DONATIONS; SLEEP; ICE
AB Background: Pica and restless legs syndrome (RLS) are associated with iron depletion and deficiency. The presence of pica and RLS was prospectively assessed in blood donors.
Study Design and Methods: During a 39-month period, 1236 donors deferred for fingerstick hemoglobin (Hb) level of less than 12.5g/dL and 400 nondeferred "control" donors underwent health screening and laboratory testing (complete blood count, ferritin, iron, transferrin). Pica and RLS were assessed by direct questioning. Deferred donors and iron-deficient control donors were given 325mg of ferrous sulfate daily for 60 days. Reassessments were performed and additional iron tablets dispensed at subsequent visits.
Results: Pica was reported in 11% of donors with iron depletion or deficiency, compared with 4% of iron-replete donors (p<0.0001). Pagophagia (ice pica) was most common and often of extraordinary intensity. Female sex, younger age, and lower mean cell volume and transferrin saturation values were strongly associated with pica. Donors with pica given iron reported a marked reduction in the desire to consume the nonnutritive substance by Days 5 to 8 of therapy, with disappearance of symptoms by Days 10 to 14. RLS was reported in 16% of subjects with iron depletion or deficiency compared with 11% of iron-replete donors (p=0.012). Iron replacement generally resulted in improvement of RLS symptoms; however, at least 4 to 6 weeks of iron therapy was necessary.
Conclusion: The presence of pica is associated with a high probability of iron depletion or deficiency in blood donors; however, RLS lacks a strong correlation in this population. Screening questions for pagophagia may be useful in the ascertainment of iron deficiency in donors and may identify those who would benefit from oral iron.
C1 NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Bryant, Barbara J.] Univ Texas Med Branch, Dept Pathol, Blood Bank Div, Galveston, TX 77555 USA.
RP Bryant, BJ (reprint author), Univ Texas Med Branch, Dept Pathol, Blood Bank Div, 301 Univ Blvd, Galveston, TX 77555 USA.
EM bbryant@utmb.edu
FU Intramural NIH HHS [Z99 CL999999]
NR 30
TC 24
Z9 25
U1 0
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
EI 1537-2995
J9 TRANSFUSION
JI Transfusion
PD AUG
PY 2013
VL 53
IS 8
BP 1637
EP 1644
DI 10.1111/trf.12061
PG 8
WC Hematology
SC Hematology
GA 197SB
UT WOS:000322869800036
PM 23305102
ER
PT J
AU Spencer, BR
Kleinman, S
Wright, DJ
Glynn, SA
Rye, DB
Kiss, JE
Mast, AE
Cable, RG
AF Spencer, Bryan R.
Kleinman, Steven
Wright, David J.
Glynn, Simone A.
Rye, David B.
Kiss, Joseph E.
Mast, Alan E.
Cable, Ritchard G.
CA REDS-II RISE Anal Grp
TI Restless legs syndrome, pica, and iron status in blood donors
SO TRANSFUSION
LA English
DT Article
ID PATHOPHYSIOLOGY; DEFICIENCY; RLS
AB BACKGROUND: The association of blood donation-related iron deficiency with pica or restless legs syndrome (RLS) remains poorly elucidated. This study evaluated the prevalence of RLS and pica in blood donors completing the REDS-II Iron Status Evaluation (RISE) study.
STUDY DESIGN AND METHODS: RISE enrolled 2425 blood donors in a prospective cohort study; 1334 donors provided blood samples to characterize iron status and answered a questionnaire inquiring into symptoms of RLS and pica at a final visit after 15 to 24 months of follow-up. Associations between both conditions and iron status were evaluated.
RESULTS: There were 9 and 20% of donors reporting symptoms of probable or probable/possible RLS, respectively. Iron depletion and donation intensity were not predictive of RLS. Pica was reported by 65 donors (5.5%), half of whom reported daily cravings. Prevalence of pica increased with degree of iron depletion in women (2% in iron-replete females, 13% in those with ferritin < 12 ng/mL), but not in men. Probable RLS and pica coexpressed in eight individuals, but no more frequently than expected by chance.
CONCLUSION: RLS and pica have been associated with iron deficiency in nondonor populations. This study indicates a potentially high prevalence of RLS in frequent blood donors but shows no association with iron status or donation intensity. Low iron stores were associated with higher prevalence of pica, but only in females. Furthermore, the results are incompatible with RLS and pica sharing a common pathophysiology.
C1 Amer Red Cross Blood Serv, Dedham, MA 02026 USA.
AABB, Bethesda, MD USA.
Westat Corp, Rockville, MD USA.
NHLBI, Bethesda, MD 20892 USA.
Emory Univ, Program Sleep, Atlanta, GA 30322 USA.
Inst Transfus Med, Pittsburgh, PA USA.
BloodCtr Wisconsin, Milwaukee, WI USA.
Amer Red Cross Blood Serv, Farmington, CT USA.
RP Spencer, BR (reprint author), Amer Red Cross, New England Reg, 180 Rustcraft Rd,Suite 115, Dedham, MA 02026 USA.
EM Bryan.Spencer@redcross.org
FU National Heart, Lung, and Blood Institute [N01HB47168, N01HB47169,
N01HB47170, N01HB47171, N01HB47172, N01HB47174, N01HB47175, N01HB57181]
FX This study was supported by Contracts N01HB47168, N01HB47169,
N01HB47170, N01HB47171, N01HB47172, N01HB47174, N01HB47175, and
N01HB57181 from the National Heart, Lung, and Blood Institute.
NR 20
TC 22
Z9 22
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD AUG
PY 2013
VL 53
IS 8
BP 1645
EP 1652
DI 10.1111/trf.12260
PG 8
WC Hematology
SC Hematology
GA 197SB
UT WOS:000322869800037
PM 23763445
ER
PT J
AU Chaux, A
Netto, GJ
Rodriguez, I
Barreto, JE
Oertell, J
Ocampos, S
Boggino, H
Codas, R
Bosch, FX
Sanjose, S
Munoz, N
Hildesheim, A
Cubilla, AL
AF Chaux, Alcides
Netto, George J.
Rodriguez, Ingrid M.
Barreto, Jose E.
Oertell, Judith
Ocampos, Sandra
Boggino, Hugo
Codas, Ricardo
Xavier Bosch, F.
de Sanjose, Silvia
Munoz, Nubia
Hildesheim, Allan
Cubilla, Antonio L.
TI Epidemiologic profile, sexual history, pathologic features, and human
papillomavirus status of 103 patients with penile carcinoma
SO WORLD JOURNAL OF UROLOGY
LA English
DT Article
DE Penile cancer; Human papillomavirus; Circumcision; Phimosis; Lichen
sclerosus; Risk factors
ID SQUAMOUS-CELL CARCINOMA; PREFERENTIAL ASSOCIATION; UNITED-STATES;
CANCER; SMOKING; GRADE
AB The incidence of penile cancer is four times higher in Paraguay than in the United States or Europe. There are no adequate scientific explanations for this geographical variation. The goal of this study was to evaluate the interplay among risk factors, morphology of the primary tumor, and HPV status.
Information on socioeconomic status, education level, habits, and sexual history was obtained in 103 Paraguayan patients with penile cancer. All patients were then treated by surgery, and specimens were evaluated histopathologically.
Patients usually dwelled in rural/suburban areas (82%), lived in poverty (75%), had a low education level (91%), and were heavy smokers (76%). Phimosis (57%), moderate/poor hygienic habits (90%), and history of sexually transmitted diseases (74%) were frequently found. Patients with > 10 lifetime female partners had an odds ratio of 3.8 (95% CI 1.1, 12.6; P-trend = .03) for presenting HPV-positive tumors when compared to patients with < 6 partners. However, this trend was not significant when the number of sexual partners was adjusted for age of first coitus and antecedents of sexually transmitted diseases. HPV-related tumors (found in 36% of the samples) were characterized by a warty and/or basaloid morphology and high histological grade in most cases.
In our series, patients with penile cancer presented a distinctive epidemiologic and pathologic profile. These data might help explaining the geographical differences in incidence and aid in the design of strategies for cancer control in Paraguay.
C1 [Chaux, Alcides; Rodriguez, Ingrid M.; Barreto, Jose E.; Oertell, Judith; Ocampos, Sandra; Boggino, Hugo; Codas, Ricardo; Cubilla, Antonio L.] Inst Patol & Invest, Asuncion, Paraguay.
[Chaux, Alcides; Netto, George J.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21231 USA.
[Xavier Bosch, F.; de Sanjose, Silvia; Munoz, Nubia] Inst Catala Oncol, Barcelona, Spain.
[de Sanjose, Silvia] CIBER Epidemiol & Salud Publ, Barcelona, Spain.
[Hildesheim, Allan] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Chaux, A (reprint author), Johns Hopkins Univ, Sch Med, Dept Pathol, 401 N Broadway Weinberg 2242, Baltimore, MD 21231 USA.
EM achaux1@jhmi.edu
RI de Sanjose Llongueras, Silvia/H-6339-2014; BOSCH JOSE, FRANCESC
XAVIER/J-6339-2012; Hildesheim, Allan/B-9760-2015;
OI BOSCH JOSE, FRANCESC XAVIER/0000-0002-7172-3412; Hildesheim,
Allan/0000-0003-0257-2363; Chaux, Alcides/0000-0002-5824-9867
FU Johns Hopkins Medicine-Patana Fund for Research
FX Dr Chaux was supported by the Johns Hopkins Medicine-Patana Fund for
Research.
NR 22
TC 18
Z9 19
U1 0
U2 14
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0724-4983
J9 WORLD J UROL
JI World J. Urol.
PD AUG
PY 2013
VL 31
IS 4
BP 861
EP 867
DI 10.1007/s00345-011-0802-0
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA 195YJ
UT WOS:000322739400025
PM 22116602
ER
PT J
AU Sebastian, S
Ang, R
Abramowitz, J
Weinstein, LS
Chen, M
Ludwig, A
Birnbaumer, L
Tinker, A
AF Sebastian, Sonia
Ang, Richard
Abramowitz, Joel
Weinstein, Lee S.
Chen, Min
Ludwig, Andreas
Birnbaumer, Lutz
Tinker, Andrew
TI The in vivo regulation of heart rate in the murine sinoatrial node by
stimulatory and inhibitory heterotrimeric G proteins
SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE
PHYSIOLOGY
LA English
DT Article
DE G protein; heart rate; sinoatrial node
ID RATE-VARIABILITY; MICE; DEPOLARIZATION; KNOCKOUT; SHIFT; HCN4
AB Reciprocal physiological modulation of heart rate is controlled by the sympathetic and parasympathetic systems acting on the sinoatrial (SA) node. However, there is little direct in vivo work examining the role of stimulatory and inhibitory G protein signaling in the SA node. Thus, we designed a study to examine the role of the stimulatory (G alpha s) and inhibitory G protein (G alpha i2) in in vivo heart rate regulation in the SA node in the mouse. We studied mice with conditional deletion of G alpha s and G alpha i2 in the conduction system using cre-loxP technology. We crossed mice in which cre recombinase expression was driven by a tamoxifen-inducible conduction system-specific construct with "G alpha s floxed" and "G alpha i2 floxed" mice. We studied the heart rate responses of adult mice compared with littermate controls by using radiotelemetry before and after administration of tamoxifen. The mice with conditional deletion of G alpha s and G alpha i2 had a loss of diurnal variation and were bradycardic or tachycardic, respectively, in the daytime. In mice with conditional deletion of G alpha s, there was a selective loss of low-frequency power, while with deletion of G alpha i2, there was a loss of high-frequency power in power spectral analysis of heart rate variability. There was no evidence of pathological arrhythmia. Pharmacological modulation of heart rate by isoprenaline was impaired in the G alpha s mice, but a muscarinic agonist was still able to slow the heart rate in G alpha i2 mice. We conclude that G alpha s- and G alpha i2-mediated signaling in the sinoatrial node is important in the reciprocal regulation of heart rate through the autonomic nervous system.
C1 [Sebastian, Sonia; Ang, Richard; Tinker, Andrew] Barts & London Queen Marys Sch Med & Dent, William Harvey Heart Ctr, London EC1M 6BQ, England.
[Abramowitz, Joel; Birnbaumer, Lutz] NIEHS, Div Intramural Res, Res Triangle Pk, NC 27709 USA.
[Weinstein, Lee S.; Chen, Min] NIDDK, Metab Dis Branch, NIH, Bethesda, MD USA.
[Ludwig, Andreas] Univ Erlangen Nurnberg, Inst Expt & Klin Pharmakol & Toxikol, D-91054 Erlangen, Germany.
RP Tinker, A (reprint author), Barts & London Queen Marys Sch Med & Dent, William Harvey Heart Ctr, Charterhouse Sq, London EC1M 6BQ, England.
EM a.tinker@qmul.ac.uk
RI Abramowitz, Joel/A-2620-2015
FU Wellcome Trust; Medical Research Council; National Institute for Health
Research Barts Cardiovascular Biomedical Research Unit; National
Institutes of Health [Z01-ES-101643]; National Institute of Diabetes and
Digestive and Kidney Diseases
FX This work was supported by the Wellcome Trust, Medical Research Council,
The National Institute for Health Research Barts Cardiovascular
Biomedical Research Unit and by the Intramural Research Program of the
National Institutes of Health (project Z01-ES-101643 to LB) and National
Institute of Diabetes and Digestive and Kidney Diseases to L. S.
Weinstein.
NR 29
TC 4
Z9 4
U1 0
U2 9
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6119
J9 AM J PHYSIOL-REG I
JI Am. J. Physiol.-Regul. Integr. Comp. Physiol.
PD AUG
PY 2013
VL 305
IS 4
BP R435
EP R442
DI 10.1152/ajpregu.00037.2013
PG 8
WC Physiology
SC Physiology
GA 205JR
UT WOS:000323440900012
PM 23697798
ER
PT J
AU Zhou, H
Kajiyama, H
Tsuji, T
Hu, XZ
Leelahavanichkul, A
Vento, S
Frank, R
Kopp, JB
Trachtman, H
Star, RA
Yuen, PST
AF Zhou, Hua
Kajiyama, Hiroshi
Tsuji, Takayuki
Hu, Xuzhen
Leelahavanichkul, Asada
Vento, Suzanne
Frank, Rachel
Kopp, Jeffrey B.
Trachtman, Howard
Star, Robert A.
Yuen, Peter S. T.
TI Urinary exosomal Wilms' tumor-1 as a potential biomarker for podocyte
injury
SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
LA English
DT Article
DE exosomes; WT-1; focal segmental glomerulosclerosis; collapsing
glomerulopathy; podocytopathy
ID HIV-ASSOCIATED NEPHROPATHY; GLOMERULAR-DISEASES; MESSENGER-RNA;
RENAL-DISEASE; PROTEIN; WT1; PODOCYTOPATHIES; PROGRESSION; DISCOVERY;
MARKER
AB Renal Wilms' tumor-1 (WT-1) staining is used to detect podocyte loss in kidney biopsies. We aimed to determine if urinary exosomal WT-1 could serve as a noninvasive biomarker of podocyte injury. We examined WT-1 by Western blot in a human podocyte-like cell line, a mouse model of podocyte injury, and human subjects with podocyte disorders. WT-1 was detected in exosomal fraction of the conditioned media from podocytes and increased 48 h after hTGF-beta 1 stimulation. Cellular WT-1 decreased in podocytes following hTGF-beta 1 incubation. In mice with induced podocyte injury, urinary exosomal WT-1 was detected 1 wk earlier than albuminuria and also tracked the effects of angiotensin receptor blocker (ARB) treatment. In addition, urinary exosomal WT-1 levels at 1 wk post-injury correlated with the severity of glomerular injury at 3 wk later. In human subjects, urinary exosomal WT-1 was significantly increased in focal segmental glomerulosclerosis (FSGS) patients compared with healthy volunteers or steroid-sensitive nephrotic syndrome (SSNS) patients. Urinary exosomal WT-1 was also significantly decreased in patients in remission for either FSGS or SSNS or following steroid treatment in six SSNS subjects. We conclude that urinary exosomal WT-1 is a promising noninvasive biomarker with apparent podocyte specificity that can detect early progression and treatment-induced regression of podocyte injury in FSGS or SSNS. These results warrant longitudinal, prospective studies in a large cohort with a range of podocyte diseases.
C1 [Zhou, Hua; Tsuji, Takayuki; Hu, Xuzhen; Leelahavanichkul, Asada; Star, Robert A.; Yuen, Peter S. T.] Natl Inst Diabet & Digest & Kidney Dis, Renal Diagnost & Therapeut Unit, Bethesda, MD USA.
[Zhou, Hua] China Med Univ, Clin Coll 1, Dept Nephrol, Shenyang, Peoples R China.
[Zhou, Hua] China Med Univ, Affiliated Hosp 1, Shenyang, Peoples R China.
[Kajiyama, Hiroshi; Kopp, Jeffrey B.] Natl Inst Diabet & Digest & Kidney Dis, Kidney Dis Sect, Bethesda, MD USA.
[Vento, Suzanne; Trachtman, Howard] Cohen Childrens Med Ctr, Dept Pediat, Div Nephrol, New Hyde Pk, NY USA.
RP Yuen, PST (reprint author), NIDDK, NIH, Renal Diagnost & Therapeut Unit, 10 Ctr Dr,Bldg 10,Rm 3N108, Bethesda, MD 20892 USA.
EM py@nih.gov
RI Yuen, Peter/B-1954-2008;
OI Yuen, Peter/0000-0001-9557-3909; Trachtman, Howard/0000-0001-7447-9489;
Kopp, Jeffrey/0000-0001-9052-186X
FU NIDDK, National Institutes of Health
FX This research was supported by the Intramural Research Program of the
NIDDK, National Institutes of Health.
NR 26
TC 22
Z9 23
U1 1
U2 8
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1931-857X
J9 AM J PHYSIOL-RENAL
JI Am. J. Physiol.-Renal Physiol.
PD AUG
PY 2013
VL 305
IS 4
BP F553
EP F559
DI 10.1152/ajprenal.00056.2013
PG 7
WC Physiology; Urology & Nephrology
SC Physiology; Urology & Nephrology
GA 205GG
UT WOS:000323430600013
PM 23761678
ER
PT J
AU Mysliwiec, V
Gill, J
Lee, H
Baxter, T
Pierce, R
Barr, TL
Krakow, B
Roth, BJ
AF Mysliwiec, Vincent
Gill, Jessica
Lee, Hyunhwa
Baxter, Tristin
Pierce, Roslyn
Barr, Taura L.
Krakow, Barry
Roth, Bernard J.
TI Sleep Disorders in US Military Personnel A High Rate of Comorbid
Insomnia and Obstructive Sleep Apnea
SO CHEST
LA English
DT Article
ID POSTTRAUMATIC-STRESS-DISORDER; TRAUMATIC BRAIN-INJURY; MENTAL-HEALTH
PROBLEMS; BREATHING DISORDERS; DAYTIME SLEEPINESS; UNITED-STATES; FIRE
EVACUEES; IRAQ; AFGHANISTAN; VETERANS
AB Background: Sleep disturbances are among the most common symptoms of military personnel who return from deployment. The objective of our study was to determine the presence of sleep disorders in US military personnel referred for evaluation of sleep disturbances after deployment and examine associations between sleep disorders and service-related diagnoses of depression, mild traumatic brain injury, pain, and posttraumatic stress disorder (PTSD).
Methods: This was a cross-sectional study of military personnel with sleep disturbances who returned from combat within 18 months of deployment. Sleep disorders were assessed by clinical evaluation and polysomnogram with validated instruments to diagnose service-related illnesses.
Results: Of 110 military personnel included in our analysis, 97.3% were men (mean age, 33.6 +/- 8.0 years; mean BMI, 30.0 +/- 4.3 kg/m(2)), and 70.9% returned from combat within 12 months. Nearly one-half (47.3%) met diagnostic criteria for two or more service-related diagnoses. Sleep disorders were diagnosed in 88.2% of subjects; 11.8% had a normal sleep evaluation and served as control subjects. Overall, 62.7% met diagnostic criteria for obstructive sleep apnea (OSA) and 63.6% for insomnia. The exclusive diagnoses of insomnia and OSA were present in 25.5% and 24.5% of subjects, respectively; 38.2% had comorbid insomnia and OSA. Military personnel with comorbid insomnia and OSA were significantly more likely to meet criteria for depression (P < .01) and PTSD (P < .01) compared with control subjects and those with OSA only.
Conclusions: Comorbid insomnia and OSA is a frequent diagnosis in military personnel referred for evaluation of sleep disturbances after deployment. This diagnosis, which is difficult to treat, may explain the refractory nature of many service-related diagnoses.
C1 [Mysliwiec, Vincent; Baxter, Tristin; Pierce, Roslyn; Roth, Bernard J.] Madigan Army Med Ctr, Tacoma, WA 98431 USA.
[Gill, Jessica; Lee, Hyunhwa] NIH, Bethesda, MD 20892 USA.
[Barr, Taura L.] W Virginia Univ, Morgantown, WV 26506 USA.
[Barr, Taura L.] Robert Wood Johnson Fdn, Morgantown, WV USA.
[Krakow, Barry] Maimonides Sleep Arts & Sci Ltd, Sleep & Human Hlth Inst, Albuquerque, NM USA.
RP Mysliwiec, V (reprint author), Madigan Army Med Ctr, Dept Pulm Crit Care & Sleep Med, 9040A Fitzsimmons Ave, Tacoma, WA 98431 USA.
EM vincent.mysliwiec.mil@mail.mil
FU Center for Neuroscience and Regenerative Medicine [60855]; intramural
department of the National Institutes of Health, National Institute of
Nursing Research
FX This study was supported, in part, by the Center for Neuroscience and
Regenerative Medicine [Grant 60855]. Funding support was provided by the
intramural department of the National Institutes of Health, National
Institute of Nursing Research (to Drs Gill and Lee).
NR 60
TC 31
Z9 31
U1 2
U2 20
PU AMER COLL CHEST PHYSICIANS
PI NORTHBROOK
PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA
SN 0012-3692
J9 CHEST
JI Chest
PD AUG
PY 2013
VL 144
IS 2
BP 549
EP 557
DI 10.1378/chest.13-0088
PG 9
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 199UQ
UT WOS:000323021400030
PM 23681455
ER
PT J
AU Terao, Y
Fukuda, H
Ugawa, Y
Hikosaka, O
AF Terao, Yasuo
Fukuda, Hideki
Ugawa, Yoshikazu
Hikosaka, Okihide
TI New perspectives on the pathophysiology of Parkinson's disease as
assessed by saccade performance: A clinical review
SO CLINICAL NEUROPHYSIOLOGY
LA English
DT Review
DE Saccade; Basal ganglia; Parkinson's disease; Superior colliculus;
Substantia nigra; Inhibition
ID NIGRA PARS RETICULATA; PROGRESSIVE SUPRANUCLEAR PALSY; MONKEY SUPERIOR
COLLICULUS; HUMAN SUBTHALAMIC NUCLEUS; VISUALLY-GUIDED SACCADES; DEEP
BRAIN-STIMULATION; INHIBITORY OCULOMOTOR CONTROL;
POSITRON-EMISSION-TOMOGRAPHY; LOCAL DOPAMINE DEPLETION; GABA-RELATED
SUBSTANCES
AB We reviewed basal ganglia (BG) dysfunction in Parkinson's disease (PD) based on recent findings on saccade performance. Hypometria in all saccade paradigms and impaired initiation of internally triggered saccades such as memory guided saccades (MGS) are reported, whereas visually guided saccades (VGS) are relatively spared, although they are also mildly affected. The ability to inhibit unwanted saccades is also impaired. We propose that three major drives converges on SC to determine the saccade abnormalities. The impairment in VGS may be caused by the excessive inhibition of SC due to the increased BG output, whereas for MGS, decreased activity of the frontal cortex-BG circuit may also be involved. The impaired suppression of unwanted saccades may result from the "leaky" inhibition of SC. When PD patients inspect pictures, they end up exploring a smaller area of them with smaller saccades compared to normal subjects. Levodopa slightly prolongs VGS latency and shortens MGS latency, by altering the balance between the direct and indirect pathways of the BG circuit. In contrast, deep brain stimulation of the subthalamic nucleus improves saccade hypometria in both VGS and MGS, presumably by acting relatively directly on the SC-substantia nigra pars reticulata pathway to remove the excessive SC inhibition. (C) 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
C1 [Terao, Yasuo] Univ Tokyo, Dept Neurol, Tokyo 1138655, Japan.
[Fukuda, Hideki] Segawa Neurol Clin Children, Tokyo, Japan.
[Ugawa, Yoshikazu] Fukushima Med Univ, Sch Med, Dept Neurol, Fukushima, Japan.
[Hikosaka, Okihide] NEI, Sect Neuronal Networks, Sensorimotor Res Lab, Bethesda, MD 20892 USA.
RP Terao, Y (reprint author), Univ Tokyo, Dept Neurol, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan.
EM yterao-tky@umin.ac.jp
FU Ministry of Education, Culture, Sports, Science, and Technology of
Japan; Magnetic Health Science Foundation; Kato Memorial Trust for
Nambyo Research, Japan
FX This work was partly supported by grants from a Research Project
Grant-in-aid for Scientific Research from the Ministry of Education,
Culture, Sports, Science, and Technology of Japan and research funds
from the Magnetic Health Science Foundation and the Kato Memorial Trust
for Nambyo Research, Japan.
NR 155
TC 22
Z9 23
U1 2
U2 17
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 1388-2457
EI 1872-8952
J9 CLIN NEUROPHYSIOL
JI Clin. Neurophysiol.
PD AUG
PY 2013
VL 124
IS 8
BP 1491
EP 1506
DI 10.1016/j.clinph.2013.01.021
PG 16
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 201TD
UT WOS:000323165000005
PM 23499161
ER
PT J
AU Kang, SY
Hallett, M
Sohn, YH
AF Kang, Suk Y.
Hallett, Mark
Sohn, Young H.
TI Exercise-induced strengthening of inter-digital connections in musicians
SO CLINICAL NEUROPHYSIOLOGY
LA English
DT Article
DE TMS; Motor-evoked potential; Musician; Surround inhibition
ID FOCAL HAND DYSTONIA; HUMAN MOTOR CORTEX; SURROUND INHIBITION;
INTRACORTICAL INHIBITION; BRAIN; PLASTICITY; MODULATION; ACTIVATION;
SYSTEM; MUSCLE
AB Objective: To investigate whether finger exercise affects surround inhibition in professional musicians as it was previously observed in non-musicians, we performed a transcranial magnetic stimulation (TMS) study in 13 healthy right-handed professional musicians.
Methods: TMS was set to be triggered by self-initiated flexion of the index finger at 3 ms after electromyography onset (self-triggered TMS). Motor evoked potentials (MEPs) of the abductor digiti minimi (ADM) were measured before and at 0, 10, 20 and 30 min after 'single' (little finger abduction) and 'dual' (both index finger flexion and little finger abduction) exercise at 0.5 Hz for 30 min.
Results: Control and self-triggered MEPs were not different between the two exercise sessions. MEP enhancements were significantly greater in self-triggered TMS than control TMS after single exercise as well as dual exercise.
Conclusion: This result demonstrates that MEP enhancement in self-triggered TMS was comparable between two exercise sessions in professional musicians, a result different from that observed in healthy non-musicians. Enhanced self-triggered MEPs after isolated finger exercise suggest that inter-digital cortical connections are strengthened in musicians, presumably due to previous musical training.
Significance: Inter-digital cortical connections are strengthened in musicians and are not differently modulated by different types of short-term finger exercise. (C) 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
C1 [Kang, Suk Y.; Sohn, Young H.] Yonsei Univ, Coll Med, Dept Neurol, Seoul 120752, South Korea.
[Kang, Suk Y.; Sohn, Young H.] Yonsei Univ, Coll Med, Brain Res Inst, Seoul 120752, South Korea.
[Kang, Suk Y.] Hallym Univ, Coll Med, Dongtan Sacred Heart Hosp, Dept Neurol, Gyunggi Do, South Korea.
[Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA.
RP Sohn, YH (reprint author), Yonsei Univ, Coll Med, Dept Neurol, 250 Seongsanno, Seoul 120752, South Korea.
EM yhsohn62@yuhs.ac
FU Brain Korea 21 Project for Medical Science, Yonsei University; NINDS
Intramural Program
FX This work was supported by the Brain Korea 21 Project for Medical
Science, Yonsei University. Dr. Hallett is supported by the NINDS
Intramural Program. The authors report no conflict of interest.
NR 22
TC 3
Z9 3
U1 2
U2 6
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 1388-2457
J9 CLIN NEUROPHYSIOL
JI Clin. Neurophysiol.
PD AUG
PY 2013
VL 124
IS 8
BP 1622
EP 1627
DI 10.1016/j.clinph.2013.01.028
PG 6
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 201TD
UT WOS:000323165000019
PM 23540416
ER
PT J
AU Hattinger, E
Zwicker, S
Ruzicka, T
Yuspa, SH
Wolf, R
AF Hattinger, Eva
Zwicker, Stephanie
Ruzicka, Thomas
Yuspa, Stuart H.
Wolf, Ronald
TI Opposing functions of psoriasin (S100A7) and koebnerisin (S100A15) in
epithelial carcinogenesis
SO CURRENT OPINION IN PHARMACOLOGY
LA English
DT Article
ID SQUAMOUS-CELL CARCINOMAS; EF-HAND TYPE; NF-KAPPA-B; BREAST-CANCER;
MAMMARY TUMORIGENESIS; MOLECULAR-CLONING; COP9 SIGNALOSOME; AP-1
ACTIVATION; MESSENGER-RNA; IN-SITU
AB The S100 protein family is involved in epithelial cell maturation and inflammation. Some S100 members are dysregulated during carcinogenesis and have been established as tumor markers. Psoriasin (S100A7) and koebnerisin (S100A15) are highly homologous proteins that have been first described in psoriasis, which is characterized by disturbed epidermal maturation and chronic inflammation. Despite their homology, both S100 proteins are distinct in expression and function through different receptors but synergize as chemoattractants and pro-inflammatory 'alarmins' to promote inflammation. Psoriasin and koebnerisin are further regulated with tumor progression in epithelial cancers. In tumor cells, high cytoplasmic expression of psoriasin and koebnerisin may prevent oncogenic activity, whereas their nuclear translocation and extracellular secretion are associated with tumor progression and poor prognosis. The present review outlines these opposing effects of psoriasin and koebnerisin in multifunctional pathways and mechanisms that are known to affect tumor cells ('seeds'), tumor environment ('soil') and tumor cell metastasis ('seeding') thereby influencing epithelial carcinogenesis.
C1 [Hattinger, Eva; Zwicker, Stephanie; Ruzicka, Thomas; Wolf, Ronald] Univ Munich, Dept Dermatol & Allergol, Munich, Germany.
[Yuspa, Stuart H.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Wolf, R (reprint author), Univ Munich, Dept Dermatol & Allergol, Munich, Germany.
EM ronald.wolf@med.uni-muenchen.de
NR 70
TC 8
Z9 8
U1 0
U2 4
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1471-4892
J9 CURR OPIN PHARMACOL
JI Curr. Opin. Pharmacol.
PD AUG
PY 2013
VL 13
IS 4
BP 588
EP 594
DI 10.1016/j.coph.2013.04.007
PG 7
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 204XY
UT WOS:000323405800016
PM 23664757
ER
PT J
AU Bornstein, MH
Arterberry, ME
Mash, C
AF Bornstein, Marc H.
Arterberry, Martha E.
Mash, Clay
TI Differentiated Brain Activity in Response to Faces of "Own" Versus
"Unfamiliar" Babies in Primipara Mothers: An Electrophysiological Study
SO DEVELOPMENTAL NEUROPSYCHOLOGY
LA English
DT Review
ID EVENT-RELATED POTENTIALS; HUMAN EXTRASTRIATE CORTEX; VISUAL
EVOKED-POTENTIALS; RECOGNITION MEMORY; MATERNAL RESPONSIVENESS;
SELECTIVE ATTENTION; POSTPARTUM PERIOD; INFANT FACES; NEURAL BASIS;
EMOTIONAL EXPRESSION
AB Experiences with one's own infant attune the parent nervous system to infant stimuli. To explore the effects of motherhood on brain activity patterns, electroencephalogram (EEG) was recorded while primipara mothers of 3- and 6-month-olds viewed images of faces of their own child and an unfamiliar but appearance-matched child. Mothers of 3- and 6-month-olds showed equivalent early-wave (N/P1 visual and N170 face-sensitive) responses to own and unfamiliar baby faces but differentiating late-wave (N/P600 familiar/novel) activity to own versus unfamiliar infant faces. Based on 3 months experience with their own infant's face, mothers' brain patterns give evidence of distinctive late-wave (recognition) sensitivity.
C1 [Bornstein, Marc H.; Mash, Clay] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
[Arterberry, Martha E.] Colby Coll, Dept Psychol, Waterville, ME 04901 USA.
RP Bornstein, MH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, 6705 Rockledge Dr,Suite 8030, Bethesda, MD 20892 USA.
EM marc_h_bornstein@nih.gov
FU NIH, NICHD
FX This research was supported by the Intramural Research Program of the
NIH, NICHD.
NR 141
TC 7
Z9 7
U1 1
U2 13
PU PSYCHOLOGY PRESS
PI HOVE
PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND
SN 8756-5641
J9 DEV NEUROPSYCHOL
JI Dev. Neuropsychol.
PD AUG 1
PY 2013
VL 38
IS 6
BP 365
EP 385
DI 10.1080/87565641.2013.804923
PG 21
WC Psychology, Developmental; Psychology; Psychology, Experimental
SC Psychology
GA 205XP
UT WOS:000323478400001
PM 23971490
ER
EF